International Journal of Medical Sciences

Optimization of 5-fluorouracil solid-lipid nanoparticles: a preliminary study to treat colon cancer

2010-11-22

Solid lipid nanoparticle (SLNs) formulae were utilized for the release of 5-fluorouracil (5-FU) inside the colonic medium for local treatment of colon cancer. SLNs were prepared by double emulsion-solvent evaporation technique (w/o/w) using triglyceride esters, Dynasan™ 114 or Dynasan™ 118 along with soyalecithin as the lipid parts. Different formulation parameters; including type of Dynasan, soyalicithin:Dynasan ratio, drug:total lipid ratio, and polyvinyl alcohol (PVA) concentration were studied with respect to particle size and drug entrapment efficiency. Results showed that formula 8 (F8) with composition of 20% 5-FU, 27% Dynasan™ 114, and 53% soyalithicin and F14 (20% 5-FU, 27% Dynasan™ 118, and 53% soyalithicin), which were stabilized by 0.5% PVA, as well as F10 with similar composition as F8 but stabilized by 2% PVA were considered the optimum formulae as they combined small particle sizes and relatively high encapsulation efficiencies. F8 had a particle size of 402.5 nm ± 34.5 with a polydispersity value of 0.005 and an encapsulation efficiency of 51%, F10 had a 617.3 nm ± 54.3 particle size with 0.005 polydispersity value and 49.1% encapsulation efficiency, whereas formula F14 showed a particle size of 343 nm ± 29 with 0.005 polydispersity, and an encapsulation efficiency of 59.09%. DSC and FTIR results suggested the existence of the lipids in the solid crystalline state. Incomplete biphasic prolonged release profile of the drug from The three formulae was observed in phosphate buffer pH 6.8 as well as simulated colonic medium containing rat caecal contents. A burst release with magnitudes of 26%, 32% and 28.8% cumulative drug released were noticed in the first hour samples incubated in phosphate buffer pH 6.8 for both F8, F10 and F14, respectively, followed by a slow release profile reaching 50%, 46.3% and 52% after 48 hours.

Surgical Removal of lipoma from an area with tattooed skin

2010-11-22

The presence of tattoos on the skin of people of all ages is on the rise. On occasion, the tattoo is in close proximity to an area which has to undergo a surgical operation, therefore why not using the tattoo itself to cover the cicatrix?

The case we treated was that of a 39 year old female who, for a couple of years, had a large lipoma on her right shoulder which she never treated because it was beneath a large tattoo. During the surgical treatment of the lipoma, we followed the exact lines of the tattoo itself thus obtaining precise access for lipoma removal which minimized visible post operative cicatrix while maintaining the original tattoo design.

No similar case was found in literature.

Prevalence of Overactive Bladder, its Under-Diagnosis, and Risk Factors in a Male Urologic Veterans Population

Wellman W Cheung, William Blank, Dorota Borawski, William Tran, Martin H Bluth — 2010-11-12

Purpose: We assess the prevalence of overactive bladder (OAB) and its risk factors in a male urologic veterans population. Materials and Methods: Validated self-administered questionnaire was prospectively given. Results: Among 1086 patients, OAB was present in 75%, of which 48% had not been diagnosed/treated. The risk of OAB increased with age. OAB was not associated with BMI, smoking, race, diabetes, CHF, and COPD. Conclusions: The prevalence of OAB in this population is under-diagnosed and under-treated.

Technical Considerations in Decompressive Craniectomy in the Treatment of Traumatic Brain Injury

X. Huang, L. Wen — 2010-11-8

Refractory intracranial hypertension is a leading cause of poor neurological outcomes in patients with severe traumatic brain injury. Decompressive craniectomy has been used in the management of refractory intracranial hypertension for about a century, and is presently one of the most important methods for its control. However, there is still a lack of conclusive evidence for its efficacy in terms of patient outcome. In this article, we focus on the technical aspects of decompressive craniectomy and review different methods for this procedure. Moreover, we review technical improvements in large decompressive craniectomy, which is currently recommended by most authors and is aimed at increasing the decompressive effect, avoiding surgical complications, and facilitating subsequent management. At present, in the absence of prospective randomized controlled trials to prove the role of decompressive craniectomy in the treatment of traumatic brain injury, these technical improvements are valuable.

Non-syndromic multiple supernumerary teeth in a family unit with a normal karyotype: case report

2010-11-5

Introduction. Hyperdontia is an odontostomatologic anomaly characterized by an excess in tooth number. It seems to occur more often in patients with hereditary factors concerning this anomaly: this case represents a rare form of hyperdontia, with bilateral multiple supernumerary teeth, with evident penetrance of the phenotype in the family unit engaged in the present study. The karyotype determination excludes a pathogenesis on chromosomal basis.

Case report. A 30 years old patient came to our observation with five impacted teeth (1.8, 2.8, 3.8, 4.7 and 4.8), as well as with the presence of an impacted supernumerary tooth (distomolar 4.9). The patient was suggested to allow us to perform a radiologic screening to his two sisters aged 17 and 13 years.

The X-ray photography showed that the elder sister had nine impacted teeth; these were 1.8 - 1.9 - 2.8 - 2.9 - 2.10 - 3.8 - 3.9 - 4.8 - 4.9; while the youngest sister had four impacted teeth, that is 1.8 - 1.9 - 2.8 - 2.9.

Conclusions. The value of the present case report can be used as a paradigm for the assessment of the hereditary factors predisposing the onset of hyperdontia, and for the consequent management by oral surgeon of family units in which the odontostomatologic anomaly was detected without any syndromic forms.

Comparative Efficacy and Tolerability of 5-Loxin® and Aflapin® Against Osteoarthritis of the Knee: A Double Blind, Randomized, Placebo Controlled Clinical Study

2010-11-1

Aflapin^® is a novel synergistic composition derived from Boswellia serrata gum resin (Indian Patent Application No. 2229/CHE/2008). Aflapin is significantly better as an anti-inflammatory agent compared to the Boswellia extracts presently available in the market. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the comparative efficacy and tolerability of 5-Loxin^® and Aflapin^® in the treatment of osteoarthritis (OA) of the knee (Clinical trial registration number: ISRCTN80793440). Sixty OA subjects were included in the study. The subjects received either 100 mg (n=20) of 5-Loxin^® or 100 mg (n=20) of Aflapin^® or a placebo (n=20) daily for 90 days. Each patient was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne's Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 7, 30, 60 and 90. A battery of biochemical parameters in serum, urine and hematological parameters in citrated whole blood were performed to assess the safety of 5-Loxin^® and Aflapin^® in OA subjects. Fifty seven subjects completed the study. At the end of the study, both 5-Loxin^® and Aflapin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA subjects. Interestingly, significant improvements in pain score and functional ability were recorded as early as 7 days after initiation of the study in the treatment group supplemented with 100 mg Aflapin. Corroborating the improvements in pain scores in treatment groups, our in vitro studies provide evidences that Aflapin^® is capable of inhibiting cartilage degrading enzyme MMP-3 and has the potential to regulate the inflammatory response by inhibiting ICAM-1. Aflapin^® and 5-Loxin^® reduce pain and improve physical functions significantly in OA subjects. Aflapin exhibited better efficacy compared to 5-Loxin^®. In comparison with placebo, the safety parameters were almost unchanged in the treatment groups. Hence both 5-Loxin^® and Aflapin^® are safe for human consumption.

Pravastatin Provides Antioxidant Activity and Protection Of Erythrocytes Loaded Primaquine

Fars Alanazi — 2010-10-28

Loading erythrocytes with Primaquine (PQ) is advantageous. However, PQ produces damage to erythrocytes through free radicals production. Statins have antioxidant action and are involved in protective effect against situation of oxidative stress. Thus the protective effect of pravastatin (PS) against PQ induced oxidative damage to human erythrocytes was investigated in the current studies upon loading to erythrocytes.

The erythrocytes were classified into; control erythrocytes, erythrocytes incubated with either 2 mM of PS or 2 mM of PQ, and erythrocytes incubated with combination of PS plus PQ. After incubation for 30 min, the effect of the drugs on erythrocytes hemolysis as well as some biomarkers of oxidative stress (none protein thiols, protein carbonyl, thiobarbituric acid reactive substance) were investigated.

Our results revealed that PS maintains these biomarkers at values similar to that of control ones. On the other hand, PQ cause significant increases of protein carbonyl by 115% and thiobarbituric acid reactive substance by 225% while non-protein thiols were significantly decreased by 112 % compared with control erythrocytes. PS pre-incubation before PQ exerts marked reduction of these markers in comparison with PQ alone. Moreover, at NaCl concentrations between 0.4% and 0.8%, PQ causes significant increase of Red Blood Cells (RBCs) hemolysis in comparison with the other groups (P<0. 001). Scanning electron micrograph indicates spherocytes formation by PQ incubation, but in the other groups the discocyte shape of erythrocytes was preserved.

The reduction of protein oxidation and lipids peroxidation by PS is related to antioxidants effect of this statin. Preservation of erythrocytes fragility and morphology by PS are related to its free radicals scavenging effect. It is concluded that pravastatin has protective effect against erythrocytes dysfunction related any situations associated with increased oxidative stress, especially when loaded with PQ.

Primary lower limb lymphedema: a focus on its functional, social and emotional impact

Emmanouil K Symvoulakis, Dimitrios I Anyfantakis, Christos Lionis — 2010-10-22

Primary lymphedema is a rare, chronic and distressing condition with negative effects on physical, social and emotional level. The purpose of these reports was to present and discuss two different cases of primary lower limb lymphedema with a focus on its physical and mental impact and on some qualitative aspects of patients' self-reported experiences. The patients were recruited as they used occasional services within the University Hospital of Heraklion (Crete, Greece). The functional and mental impact of primary lymphedema was measured using the generic Medical Outcome Study short form-36 questionnaire and open-ended questions led to give more emphasis to patients' experiences. The analysis of short form-36 results in the first patient disclosed a significant functional impairment with a minor impact of the condition on emotional and social domains. For the second patient quality of life scores in the emotional and social domains were affected. Our findings support further the statement that physicians should pay full attention to appraise the patient's physical and emotional condition. General practitioners have the opportunity to monitor the long-term impact of chronic disorders. Posing simple open-ended questions and assessing the level of physical and mental deficits in terms of well-being through the use of specific metric tools can effectively follow-up rare conditions in the community.

Refractive Status and Prevalence of Refractive Errors in Suburban School-age Children

2010-10-18

Objective: This study investigated the distribution pattern of refractive status and prevalence of refractive errors in school-age children in Western China to determine the possible environmental factors. Methods: A random sampling strategy in geographically defined clusters was used to identify children aged 6-15 years in Yongchuan, a socio-economically representative area in Western China. We carried out a door-to-door survey and actual eye examinations, including visual acuity measurements, stereopsis examination, anterior segment and eyeball movements, fundus examinations, and cycloplegic retinoscopy with 1% cyclopentolate. Results: A total of 3469 children living in 2552 households were selected, and 3070 were examined. The distributions of refractive status were positively-skewed for 6-8-year-olds, and negatively-skewed for 9-12 and 13-15-year-olds. The prevalence of hyperopia (≥+2.00 D spherical equivalent [SE]), myopia (≤-0.50 D SE), and astigmatism (≥1.00 diopter of cylinder [DC]) were 3.26%, 13.75%, and 3.75%, respectively. As children's ages increased, the prevalence rate of hyperopia decreased (P<0.001) and that of myopia increased significantly (P<0.001). Children in academically challenging schools had a higher risk of myopia (P<0.001) and astigmatism (≥1.00DC, P =0.04) than those in regular schools. Conclusion: The distribution of refractive status changes gradually from positively-skewed to negatively-skewed distributions as age increases, with 9-year-old being the critical age for the changes. Environmental factors and study intensity influence the occurrence and development of myopia.

A severe coarctation of aorta in a 52-year-old male: a case report

Davran Cicek, Cevahir Haberal, Suleyman Ozkan, Haldun Muderrisoglu — 2010-10-8

Aortic coarctation is a congenital malformation of the aorta usually diagnosed and corrected early in life. Long-term survival is exceptional in patients with untreated aortic coarctation. In this case report, we present a late diagnosis of aortic coarctation in a 52-year-old male. Our patient was relatively asymptomatic until he presented with exertional dyspnea and fatigue in his fifth decade of life. The patient was managed by surgery of aorta. After the 1-year follow-up visit, the patient was in good clinical condition.

A cyclic-RGD-BioShuttle functionalized with TMZ by DARinv “Click Chemistry” targeted to αvβ3 integrin for therapy

2010-9-21

Clinical experiences often document, that a successful tumor control requires high doses of drug applications. It is widely believed that unavoidable adverse reactions could be minimized by using gene-therapeutic strategies protecting the tumor-surrounding healthy tissue as well as the bone-marrow. One new approach in this direction is the use of “Targeted Therapies” realizing a selective drug targeting to gain effectual amounts at the target site, even with drastically reduced application doses. MCF-7 breast cancer cells expressing the α_vβ₃ [alpha(v)beta(3)] integrin receptor are considered as appropriate candidates for such a targeted therapy. The modularly composed BioShuttle carrier consisting of different units designed to facilitate the passage across the cell membranes and for subcellular addressing of diagnostic and/or therapeutic molecules could be considered as an eligible delivery platform. Here we used the cyclic RGD-BioShuttle as a carrier for temozolomide (TMZ) at the α_vβ₃ integrin receptor realizing local TMZ concentrations sufficient for cell killing. The IC50 values are 12 µMol/L in the case of cRGD-BioShuttle-TMZ and 100 µMol/L for underivatized TMZ, which confirms the advantage of TMZ reformulation to realize local concentrations sufficient for cell killing.

Our paper focuses on the design, synthesis and application of the cRGD-BioShuttle conjugate composed of the cyclic RGD, a α_vβ₃ integrin-ligand, ligated to the cytotoxic drug TMZ. The ligation was carried out by the Diels Alder Reaction with inverse electron demand (DAR_inv).

Influenza Vaccination: Healthcare Workers Attitude in Three Middle East Countries

Eman Abu-Gharbieh, Sahar Fahmy, Bazigha Abdul Rasool, Saeed Khan — 2010-9-21

Background: Healthcare workers (HCWs) pose a potential risk of transmitting communicable diseases in the hospital settings where they usually work. This study aims to determine the current influenza vaccination rates among HCWs in three Middle East countries namely United Arab Emirates (UAE), Kuwait and Oman, and also to identify the different variables associated with the noncompliance of HCWs to the recommendations of the Advisory Committee on Immunization Practices (ACIP) set in those countries. Methods: 1500 questionnaires were distributed to health care workers in the three countries during the period of July-October 2009. Results: Among 993 respondents, the vaccination rate was 24.7%, 67.2% and 46.4% in UAE, Kuwait and Oman, respectively. The different motivating factors that influenced the health care workers to take the vaccine was assessed and found that the most common factor that influenced their decision to take the vaccine was for their self protection (59%). On the other hand, the most common reason that discouraged HCWs to take the vaccine was “lack of time” as reported by 31.8% of the respondents. Other reasons for not taking the vaccine were unawareness of vaccine availability (29.4%), unavailability of vaccine (25.4%), doubts about vaccine efficacy (24.9%), lack of information about importance (20.1%) and concerns about its side effects (17.3%). Conclusions: influenza immunization by healthcare workers in the studied countries was suboptimal which could be improved by setting different interventions and educational programs to increase vaccination acceptance among HCWs.

Severe Anisocoria after Oral Surgery under General Anesthesia

2010-9-10

Introduction. Anisocoria indicates a difference in pupil diameter. Etiologies of this clinical manifestation usually include systemic causes as neurological or vascular disorders, and local causes as congenital iris disorders and pharmacological effects.

Case Report. We present a case of a 47-year-old man, suffering from spastic tetraparesis. After the oral surgery under general anesthesia, the patient developed severe anisocoria: in particular, a ~4mm diameter increase of the left pupil compared to the right pupil.

We performed Computed Tomography (CT) in the emergency setting, Nuclear magnetic resonance (NMR) of the brain and Magnetic Resonance Angiography of intracranial vessels. These instrumental examinations did not show vascular or neurological diseases. The pupils returned to their physiological condition (isocoria) after about 180 minutes.

Discussion and Conclusions. Literature shows that the cases of anisocoria reported during or after oral surgery are rare occurrences, especially in cases of simple tooth extraction. Anisocoria can manifest in more or less evident forms: therefore, it is clear that knowing this clinical condition is of crucial importance for a correct and timely resolution.

Clinical Strategy for the Management of Solid Pseudopapillary Tumor of the Pancreas: Aggressive or Less?

Hong Chang, Yi Gong, Jian Xu, Zhongxue Su, Chengkun Qin, Zhenhai Zhang — 2010-9-1

Objective: To further delineate the clinicopathological and radiological features of solid pseudopapillary tumor (SPT) of the pancreas and summarize the surgical therapy strategy for this tumor. Methods: A retrospective review of 18 pathologically confirmed cases of SPT was performed and the clinical and pathological features, radiological findings and surgical interventions were analyzed. Results: The patients included 17 females and 1 male with a median age of 23 years. The median diameter of the lesions was 8.0 cm. Abdominal pain was the predominant complaint (8/18). The rest of the patients were asymptomatic and presented with a pancreatic mass detected incidentally. Radiological study revealed a well-demarcated mass which was composed of a solid-cystic portion. On post-contrast CT, the solid portions could be enhanced whereas the cystic parts remained unenhanced. With the preoperative diagnosis of SPT in 11 patients and pancreatic cyst, benign or malignant pancreatic tumor in the rest, pancreatic tumor resection was successfully completed. Surgical exploration findings, pathological characteristics and good prognosis of the patients with SPT, indicated its low-grade malignant potential. Conclusion: In combination with clinical findings, radiological features of SPT may help to make the correct diagnosis and differentiation from other pancreatic neoplasms. Once diagnosed, given the excellent prognosis and low-grade malignancy, less aggressive surgical resection of the primary lesion is proposed.

Genetic polymorphism of p53, but not GSTP1, is association with susceptibility to esophageal cancer risk - A Meta-Analysis

2010-9-1

A number of studies have evaluated two functional polymorphisms on p53 Arg72Pro and GSTP1 Ile105Val, in relation to esophageal cancer susceptibility. However, the results remain conflicting rather than conclusive. This meta-analysis on 2919 cases and 4074 controls for p53 Arg72Pro and 1885 cases and 2194 controls for GSTP1 Ile105Val from 13 published case-control studies showed that no significant general main effects for GSTP1 Ile105Val on esophageal cancer risk. However, we found that the p53 Arg72Pro was associated with an increased risk of esophageal cancer ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.20, 95%CI=1.06-1.36) without any between-study heterogeneity.

In the stratified analysis by ethnicity, we found that the increased esophageal cancer risk associated with p53 Arg72Pro polymorphism was more evident in Asian group ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.35, 95%CI=1.14-1.60, P=0.09 for heterogeneity test), although we still failed to find any significant association between GSTP1 Ile105Val polymorphism and esophageal cancer risk in different ethnicity. These results suggest that p53 Arg72Pro polymorphism, but not GSTP1 Ile105Val, may contribute to esophageal cancer development, especially in Asian. Additional well-designed large studies were required for the validation of this association.

1, 25-dihydroxyvitamin D3 decreases adriamycin-induced podocyte apoptosis and loss

Min-shu Zou, Jian Yu, Guo-ming Nie, Wei-sun He, Li-man Luo, Hong-tao Xu — 2010-8-24

Background: Selective proteinuria is frequently observed in glomerular diseases characterized by podocyte injury. Although, 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] has potential therapeutic effects on chronic kidney diseases through decreasing podocyte loss, the mechanism underlying the beneficial effects of 1,25(OH)₂D₃ on podocytes remains still unknown. The present study tested the hypothesis that 1,25(OH)₂D₃ directly reduced podocyte apoptosis and loss.

Methods: Sprague-Dawley (SD) rats were randomly assigned into three groups: Adriamycin (ADR) group (n=15), ADR+1,25-(OH)₂D₃ group (n=16), and control group (n=16). Rats in ADR+1,25-(OH)₂D₃ group were treated with 1,25(OH)₂D₃ for 8 weeks. The number of podocytes and foot process width (FPW) were detected by transmission electron microscopy. The number of apoptotic podocytes per glomerulus and that of apoptotic nuclei and caspase-3 activity in cultured podocytes were determined by TUNEL staining. The average number of podocytes per glomerulus was quantified by immunohistochemistry. Expressions of p-Smad2/3, p-Smad1/5/8, Fas, Fas-Associated protein with Death Domain (FADD), Bax, and Bcl-2 proteins were examined by Western blot assay.

Results: Compared with control group, proteinuria, FPW, apoptotic podocytes, caspase-3 activity, the protein expressions of p-Smad2/3, Fas, FADD, and Bax were significantly increased, podocyte density, p-Smad1/5/8 and Bcl-2 expression were decreased in ADR group. 1,25(OH)₂D₃ significantly reduced proteinuria, FPW, caspase-3 activity, expressions of p-Smad2/3, Fas, FADD, and Bax and apoptosis of podocytes, but increased serum albumin, number of viable podocytes , p-Smad1/5/8 and Bcl-2 expression in ADR treated rats.

Conclusion: ADR-induced podocyte apoptosis was associated with the imbalance of p-Smad2/3, p-Smad1/5/8 the activity of caspase-3 and aberrant expressions of, Fas, FADD, Bax and Bcl-2. The beneficial effects of 1,25(OH)₂D₃on podocytes may be attributable to inhibit podocyte apoptosis and the amelioration of podocytopenia.

Pathogenic Mechanisms Shared between Psoriasis and Cardiovascular Disease

Ramin Ghazizadeh, Hajime Shimizu, Mamiko Tosa, Mohammad Ghazizadeh — 2010-8-19

Psoriasis is associated with an increased risk of cardiovascular disease, a hallmark of which is atherosclerosis. The objective of this study was to review the pertinent literature and highlight pathogenic mechanisms shared between psoriasis and atherosclerosis in an effort to advocate early therapeutic or preventive measures. We conducted a review of the current literature available from several biomedical search databases focusing on the developmental processes common between psoriasis and atherosclerosis. Our results revealed that the pathogenic mechanisms shared between the two diseases converged onto “inflammation” phenomenon. Within the lymph nodes, antigen-presenting cells activate naive T-cells to increase expression of LFA-1 following which activated T-cells migrate to blood vessel and adhere to endothelium. Extravasation occurs mediated by LFA-1 and ICAM-1 (or CD2 and LFA-3) and activated T-cells interact with dendritic cells (and macrophages and keratinocytes in psoriasis or smooth muscle cells in atherosclerosis). These cells further secrete chemokines and cytokines that contribute to the inflammatory environment, resulting in the formation of psoriatic plaque or atherosclerotic plaque. Additionally, some studies indicated clinical improvement in psoriasis condition with treatment of associated hyperlipidemia. In conclusion, therapeutic or preventive strategies that both reduce hyperlipidemia and suppress inflammation provide potentially useful approaches in the management of both diseases.

Carotid Intima-media thickness in childhood and adolescent obesity relations to abdominal obesity, high triglyceride level and insulin resistance

Jie Fang, Jian Ping Zhang, Cai Xia Luo, Xiao Mei Yu, Lan Qiu Lv — 2010-8-18

Aim: To investigate risk factors which impact on common carotid artery intima media thickness (IMT).

Methods: A total of 86 obese children and adolescents and 22 healthy children and adolescents with normal weight were enrolled. Moreover, 23 of 86 obese children and adolescents were diagnosed with metabolic syndrome (MetS). The clinical, biochemical data and the IMT of the common carotid artery were measured in all subjects.

Results: Obese and obese with MetS subjects demonstrated a significantly (p < 0.01) thicker intima media (0.69mm, 0.66mm) as compared to the control group (0.38mm), but there was no significant difference of IMT between obese and MetS group. IMT was correlated to body weight, body mass index, waist circumference, waist to hip ratio, systolic blood pressure, diastolic blood pressure, fasting insulin, homoeostasis model assessment-insulin resistance, triglyceride, high-density lipoprotein- cholesterol, low-density lipoprotein-cholesterol, alanine aminotransferase, aspartate aminotransferase and fatty liver. Waist circumference, waist to hip ratio, triglyceride and homoeostasis model assessment-insulin resistance were independent determinants of mean IMT level.

Conclusion: Obesity especially abdominal obesity, high TG and insulin resistance may be the main risk predictors of increased IMT.

Predictors of hepatic steatosis in HBeAg-negative chronic hepatitis B patients and their diagnostic values in hepatic fibrosis

Rui-dan Zheng, Cheng-run Xu, Li Jiang, Ai-xia Dou, Kun Zhou, Lun-gen Lu — 2010-8-11

Objective: To investigate predictors of hepatic steatosis in HBeAg-negative chronic hepatitis B (CHB) patients and their diagnostic values in hepatic inflammation and fibrosis. Methods: A total of 106 HBeAg-negative CHB patients with clinically and pathologically proven steatosis and 98 patients without steatosis were recruited into this study. The levels of fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), cholesterol (CHOL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), globulin (Glb), HBV DNA, body mass index (BMI), homeostatic model assessment of insulin resistance (HOMA-IR) and pathological changes of the liver in inflammation, fibrosis and fatty deposition were examined in all patients. Results: The levels of BMI, HOMA-IR, FBG, insulin, TG, and CHOL were significantly higher in patients with steatosis than those without steatosis (all P<0.05). But ALT, AST and HBV DNA levels were significantly lower in patients with steatosis (all P<0.05). Logistic regression analysis showed that only FINS was a significant predictor for hepatic steatosis (P<0.05); FINS and Glb were significant predictors for hepatic inflammation (all P<0.05); BMI and TC were significant predictors for hepatic fibrosis (all P<0.05). Conclusions: Hepatic steatosis, a common disease in HBeAg-negative CHB patients, was positively associated with BMI, FBG, FINS, TG, TC, GGT, ALP and HOMA-IR. In these patients, the prevalence of hepatic inflammation and fibrosis was also increased.

Treatment of oroantral fistula with autologous bone graft and application of a non-reabsorbable membrane

2010-8-11

Aim: The aim of the current report is to illustrate an alternative technique for the treatment of oroantral fistula (OAF), using an autologous bone graft integrated by xenologous particulate bone graft.

Background: Acute and chronic oroantral communications (OAC, OAF) can occur as a result of inadequate treatment. In fact surgical procedures into the maxillary posterior area can lead to inadvertent communication with the maxillary sinus. Spontaneous healing can occur in defects smaller than 3 mm while larger communications should be treated without delay, in order to avoid sinusitis. The most used techniques for the treatment of OAF involve buccal flap, palatal rotation - advancement flap, Bichat fat pad. All these surgical procedures are connected with a significant risk of morbidity of the donor site, infections, avascular flap necrosis, impossibility to repeat the surgical technique after clinical failure, and patient discomfort.

Case presentation: We report a 65-years-old female patient who came to our attention for the presence of an OAF and was treated using an autologous bone graft integrated by xenologous particulate bone graft. An expanded polytetrafluoroethylene titanium-reinforced membrane (Gore-Tex ®) was used in order to obtain an optimal reconstruction of soft tissues and to assure the preservation of the bone graft from epithelial connection.

Conclusions: This surgical procedure showed a good stability of the bone grafts, with a complete resolution of the OAF, optimal management of complications, including patient discomfort, and good regeneration of soft tissues.

Clinical significance: The principal advantage of the use of autologous bone graft with an expanded polytetrafluoroethylene titanium-reinforced membrane (Gore-Tex ®) to guide the bone regeneration is that it assures a predictable healing and allows a possible following implant-prosthetic rehabilitation.

Changes of uterine blood flow after vaginal radical trachelectomy (VRT) in patients with early-stage uterine invasive cervical cancer

2010-8-5

Background. Vaginal radical trachectomy (RT) ligates and cuts several arteries supplying the uterus. Changes of blood supply to the uterus in two patients who experienced pregnancy and delivery were studied by using 3-D CT scanning. Effects of changes of blood supply to the uterus on the pregnancy courses were also examined.

Methods. Vascular distribution in the uterus was studied in two patients who received vaginal RT after delivery. Effects of changes of vascular distribution after vaginal RT were studied with respect to pregnancy courses and cervical functions.

Results. New arterial vascularization from the ascending branches of uterine arteries or other arteries occurred, and these new vessels seemed to supply blood to the remaining cervix. Differences of fetal growth and histopathological changes in the placenta between the two patients could not be detected.

Conclusion. Ligation and cutting of several supplying arteries by RT induces new areterial vascularization and it does not seem to affect fetal growth and placental function.

Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain

2010-8-2

Background: Neuropathic pain is characterized by hyperalgesia, allodynia and spontaneous pain. It often occurs as a result of injury to peripheral nerves, dorsal root ganglions (DRG), spinal cord, or brain. Recent studies have suggested that Toll-like receptor 4 (TLR4) might play a role in neuropathic pain. Methodology/Principal Findings: In this study, we investigated the role of TLR4 in a rat chronic constriction injury (CCI) model and explored the feasibility of treating neuropathic pain by inhibiting TLR4. Our results demonstrated that intrathecal siRNA-mediated suppression of TLR4 attenuated CCI-induced mechanical allodynia and thermal hyperalgesia through inhibiting the activation of NF-κB p65 and production of proinflammatory cytokines (e.g., TNF-α and IL-1β). Conclusions/Significance: These findings suggest that suppression of TLR4 mediated by intrathecally administered siRNA may be a new strategy for the treatment of neuropathic pain.

Post-traumatic glioma: Report of one case and review of the literature

Bo Zhou, Weiguo Liu — 2010-7-29

We report one case of brain glioma that developed in the scar of an old brain trauma. A 45-year-old man who presented with seizures; MRI showed a large mass in the right temporal region. Surgical biopsy showed a glioblastoma multiforme. The patient had suffered a cranial trauma in a road accident 10 years previously with an intracerebral hematoma in the right temporal region. This case fulfills the established criteria for a traumatic origin of brain tumors and adds further support to the relationship between cranial trauma and the onset of glioma. As stated by other authors, an association between head trauma and brain tumor risk cannot be ruled out and should be studied further.

Surgical Management of Hidradenitis Suppurativa

Adnan Menderes, Ozgur Sunay, Haluk Vayvada, Mustafa Yilmaz — 2010-7-19

Background: Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory disease of skin, characterized by recurrent draining sinuses and abscesses, predominantly in skin folds carrying terminal hairs and apocrine glands.

Method: This study reviewed 54 sites in 27 patients with moderate to extensive chronic inflammatory skin lesions treated surgically in our hospital from 2004 through 2009, with a follow-up of at least 6 months.

Result: A total number of 54 operative procedures were performed during the study period with 42% (23 sites) involving the axilla, 20% (11 sites) involving the gluteal area, %24 (13 sites) involving the perineal area and 12% (7 sites) involving the inguinal region.

Conclusion: Conservative treatment methods have little or no effects especially on gluteal, perineal/perianal, axillary hidradenitis suppurativa. The morbidity associated with the established form of this disease is significant, and the only successful treatment is wide surgical excision.

Influence of Cyclodextrin Complexation with NSAIDs on NSAID/Cold Stress-Induced Gastric Ulceration in Rats

2010-7-5

The aim of this work was to study the ability of β-cyclodextrin (β-CD) or hydroxypropyl β-cyclodextrin (HP-β-CD) to ameliorate the induction of gastric ulcers by a nonsteroidal anti-inflammatory drug, indomethacin or piroxicam, in rats exposed to restraint and hypothermic stress at 4 °C. Using oral gavage, rats fasted for 72 h were administered the equivalent of a 100 mg/kg dose of the assigned drug, alone or with the designated cyclodextrin (CD). The rats were placed in suitable rodent restrainers and then placed inside a ventilated refrigerator maintained at a temperature of 4 °C. Six hours later, each animal was removed, anaesthetized with ether, and the abdomen opened. Each stomach was removed, opened along the greater curvature and gently rinsed with isotonic saline solution. The induced gastric ulcers were examined and assessed with the help of a 10x binocular magnifier. Pronounced and marked gastric ulceration with complete loss of the mucosa, extensive deposition of fibrin and dense neutrophilic infiltrate were observed in rats treated with each of the drugs alone. Treatment with indomethacin or piroxicam alone induced ulcer indices of 26 ± 2.3 or 14 ± 1.8, respectively. However, β-CD and HP-β-CD each significantly suppressed ulceration due to restraint and cold stress. Rats treated with indomethacin or piroxicam in the presence of either β-CD or HP-β-CD exhibited normal tissues. Therefore, β-CD and HP-β-CD act as protective agents against gastrointestinal disorders produced by restraint and cold stress, even with the added stress from administration of either indomethacin or piroxicam.

Line bisection performance in patients with generalized anxiety disorder and treatment-resistant depression

Wei HE, Hao CHAI, Yingchun ZHANG, Shaohua YU, Wei CHEN, Wei WANG — 2010-7-2

Background and Objectives The line bisection error to the left of the true center has been interpreted as a relative right hemisphere activation, which might relate to the subject's emotional state. Considering that patients with generalized anxiety disorder (GAD) or treatment-resistant depression (TRD) often have negative emotions, we hypothesized that these patients would bisect lines significantly leftward. Methods We tried the line bisection task in the right-handed healthy volunteers (n = 56), GAD (n = 47) and TRD outpatients (n = 52). Subjects also completed the Zuckerman - Kuhlman Personality Questionnaire, the Zuckerman Sensation Seeking Scales, and the Plutchik-van Praag Depression Inventory. Results GAD patients scored highest on the Neuroticism-Anxiety trait, TRD patients scored highest on depression, and both patients scored lower on the Sociability trait. Patients with GAD also bisected lines significantly leftward compared to the healthy subjects. The Frequency of the bisection error was negatively correlated with Disinhibition-Seeking in the healthy subjects, and with Total sensation-seeking and Experience-Seeking in GAD patients, while the Magnitude of the line bisection error was negatively correlated with depression in TRD patients. Conclusions The study suggests a stronger right hemispheric activation, a weaker left activation, or both in the GAD, instead of TRD patients.

Extension of the PNA world by functionalized PNA monomers eligible candidates for inverse Diels Alder Click Chemistry

2010-6-27

Progress in genome research led to new perspectives in diagnostic applications and to new promising therapies. On account of their specificity and sensitivity, nucleic acids (DNA/RNA) increasingly are in the focus of the scientific interest. While nucleic acids were a target of therapeutic interventions up to now, they could serve as excellent tools in the future, being highly sequence-specific in molecular diagnostics. Examples for imaging modalities are the representation of metabolic processes (Molecular Imaging) and customized therapeutic approaches (“Targeted Therapy”). In the individualized medicine nucleic acids could play a key role; this requires new properties of the nucleic acids, such as stability. Due to evolutionary reasons natural nucleic acids are substrates for nucleases and therefore suitable only to a limited extent as a drug. To use DNA as an excellent drug, modifications are required leading e.g. to a peptide nucleic acid (PNA). Here we show that an easy substitution of nucleobases by functional molecules with different reactivity like the Reppe anhydride and pentenoic acid derivatives is feasible. These derivatives allow an independent multi-ligation of functionalized compounds, e.g. pharmacologically active ones together with imaging components, leading to local concentrations sufficient for therapy and diagnostics at the same time. The high chemical stability and ease of synthesis could enhance nucleic chemistry applications and qualify PNA as a favourite for delivery. This system is not restricted to medicament material, but appropriate for the development of new and highly efficient drugs for a sustainable pharmacy.

A case of mistaken identity: Asystole causing convulsions identified using implantable loop recorder.

Khalil Kanjwal, Beverly Karabin, Yousuf Kanjwal, Blair P Grubb — 2010-6-21

We present herein an interesting tracing of a patient who suffered from recurrent episodes of transient loss of consciousness (TLOC) associated with convulsive activity thought to be due to epilepsy or conversion disorder.

Preparation of RGD-modified Long Circulating Liposome Loading Matrine, and its in vitro Anti-cancer Effects

2010-6-14

Aim: To prepare RGD-modified long circulating liposome (LCL) loading matrine (RGD-M-LCL) to improve the tumor-targeting and efficacy of matrine. Methods: LCL which was prepared with HSPC, cholesterol, DSPE-PEG2000 and DSPE-PEG-MAL was modified with an RGD motif confirmed by high performance liquid chromatography (HPLC). The encapsulation efficiency of RGD-M-LCL was also detected by HPLC. MTT assay was used to examine the effects of RGD-M-LCL on the proliferation of Bcap-37, HT-29 and A375 cells. The percentage of apoptotic cells and morphological changes in Bcap-37 cells treated with RGD-M-LCL were detected by Annexin-V-FITC/PI affinity assay and observed under light microscope, respectively. Results: Spherical or oval single-chamber particles of uniform sizes with little agglutination or adhesion were observed under transmission electronic microscope. The RGD motif was successfully coupled to the DSPE-PEG-MAL on liposomes, as confirmed by HPLC. An encapsulation efficiency of 83.13% was obtained when the drug-lipid molar ratio was 0.1, and the encapsulation efficiency was negatively related to the drug-lipid ratio in the range of 0.1~0.4, and to the duration of storage. We found that, compared with free matrine, RGD-M-LCL had much stronger in vitro activity, leading to anti-proliferative and pro-apoptotic effects against cancer cells (P<0.01). Conclusion: RGD-M-LCL, a novel delivery system for anti-cancer drugs, was successfully prepared, and we demonstrated that the use of this material could augment the effects of matrine on cancer cells in vitro.

Efficacy of Sirolimus-Eluting Stents Compared With Paclitaxel-Eluting Stents in an Unselected Population With Coronary Artery Disease: 24-Month Outcomes of Patients in a Prospective Non-randomized Registry in Southern Turkey

2010-6-10

Background: The efficacy of drug-eluting stents has been shown in randomized trials, but some controversy exists regarding which stent sirolimus-eluting or paclitaxel-eluting is more effective in unselected Turkish patients. Therefore, we investigated the clinical outcomes of patients who were treated with one type of these drug-eluting stents in the real world.

Methods: We created a registry and prospectively analyzed data on a consecutive series of all patients who presented to our institution with symptomatic coronary artery disease between February 2005 and March 2007 and who were treated with the sirolimus- or the paclitaxel-eluting stent. The follow-up period after stent implantation was approximately 24 months. The primary end point was a major cardiac event, and the secondary end point was stent thrombosis. Informed consent was obtained from all subjects, and the study protocol was approved by the local ethical committee.

Results: In total, 204 patients were treated with either the sirolimus-eluting stent (n = 103) or the paclitaxel-eluting stent (n = 101). The lesions in the 2 arms of the study were treated similarly by conventional technique. At 24-month follow-up, patients who received the paclitaxel-eluting stent showed significantly higher rates of non-Q-wave myocardial infarction (1.9% vs 5.9%; P: .002), target vessel revascularization (1.9% vs 4.9%; P: .002), coronary artery bypass graft surgery (1.9% vs 6.9%; P: .001), and late stent thrombosis (1.9% vs 3.9%, P: .002).

Conclusions: Patients who received the sirolimus-eluting stent showed better clinical outcomes compared with those who had the paclitaxel-eluting-stent.

ISOLATION OF CHLAMYDIA PNEUMONIAE FROM SERUM SAMPLES OF THE PATIENTS WITH ACUTE CORONARY SYNDROME

2010-6-10

BACKGROUND: Limited body of evidence suggests that lipopolysaccharide of C. pneumoniae as well as C. pneumoniae-specific immune complexes can be detected and isolated from human serum. The aim of this study was to investigate the presence of viable elementary bodies of C.pneumoniae in serum samples of patients with acute coronary syndrome and healthy volunteers.

MATERIAL AND METHODS: Serum specimens from 26 healthy volunteers and 56 patients with acute coronary syndrome were examined subsequently by serological (C.pneumoniae-specific IgA and IgG), PCR-based and bacteriological methods. Conventional, nested and TaqMan PCR were used to detect C.pneumoniae genetic markers (ompA and 16S rRNA) in DNA from serum specimens extracted with different methods. An alternative protocol which included culturing high-speed serum sediments in HL cells and further C.pneumoniae growth evaluation with immunofluorescence analysis and TaqMan PCR was established. Pellet fraction of PCR-positive serum specimens was also examined by immunoelectron microscopy.

RESULTS: Best efficiency of final PCR product recovery from serum specimens has been shown with specific C. pneumoniae primers using phenol-chloroform DNA extraction protocol. TaqMan PCR analysis revealed that human serum of patients with acute coronary syndrome may contain genetic markers of C. pneumoniae with bacterial load range from 200 to 2000 copies/ml serum. However, reliability and reproducibility of TaqMan PCR were poor for serum specimens with low bacterial copy number (<200 /ml). Combination of bacteriological, immunofluorescence and PCR- based protocols applied for the evaluating HL cells infected with serum sediments revealed that 21.0 % of the patients with acute coronary syndrome have viable forms C.pneumoniae in serum. The detection rate of C.pneumoniae in healthy volunteers was much lower (7.7%). Immunological profile of the patients did not match accurately C.pneumoniae detection rate in serum specimens. Elementary bodies of C.pneumoniae with typical ultrastructural characteristics were also identified in serum sediments using immunoelectron microscopy.

Conclusions: Viable forms C. pneumoniae with typical electron microscopic structure can be identified and isolated from serum specimens of the patients with acute coronary syndrome and some healthy volunteers. Increased detection rate of C. pneumoniae in serum among the patients with an acute coronary syndrome may contribute towards enhanced pro-inflammatory status in cardiovascular patients and development of secondary complications of atherosclerosis.

Maitake Mushroom Extracts Ameliorate Progressive Hypertension and Other Chronic Metabolic Perturbations in Aging Female Rats

Harry G. Preuss, Bobby Echard, Debasis Bagchi, Nicholas V. Perricone — 2010-6-7

Objective: We assessed the ability of two commercially-available fractions labeled SX and D derived from the edible maitake mushroom to overcome many age-associated metabolic perturbations such as progressive, age-related elevation of blood pressure, over activity of the renin-angiotensin system (RAS), decreased insulin sensitivity, and inflammation in an in vivo laboratory model.

Design and Method: We divided forty mature, female Sprague-Dawley rats (SD) into five groups of eight. SD ingested regular rat chow containing added sucrose (20% w/w). The groups received baseline diet alone (control) or baseline diet containing captopril, niacin-bound chromium, maitake fraction SX, or maitake fraction D. In addition to blood pressure readings, the following procedures were implemented: losartan and insulin challenges, evaluation of serum ACE activity, glucose tolerance testing, blood chemistries, LNAME challenge, and measurement of various circulating cytokines.

Results: We found that implementation of all test conditions stopped the gradual elevation of systolic blood pressure (SBP) in the SD over the four months of study, even reversing some of the previous elevation that occurred over time. In general, the treatment groups showed decreased activity of the RAS estimated by less lowering of SBP after losartan challenge and decreased serum ACE activity and were more sensitive to exogenous insulin challenge. TNFa levels decreased in all four test groups suggesting a lessening of the inflammatory state.

Conclusions: We believe our data suggest that maitake mushroom fractions lessen age-related hypertension, at least in part, via effects on the RAS; enhance insulin sensitivity; and reduce some aspects of inflammation -- actions that should lead to a longer, healthier life span.

CEO- CNE Relationships: Building an Evidence-Base of Chief Nursing Executive Replacement Costs

Darlene Sredl, Niang-Huei Peng — 2010-6-3

OBJECTIVE: Explore professional relationships between Chief Nurse Executives (CNEs) and Chief Executive Officers (CEOs); CNE ethnic diversity; and CNE replacement costs.

BACKGROUND: Theoretical frameworks - Marilyn Ray's Theory of Bureaucratic Caring, and Turkel's Theory of Relational Complexity espousing economic as well as caring variables.

METHODS: Exploratory mixed-method descriptive design using CNE mailed survey.

RESULTS: CNE- cited opportunities for maintaining a positive relationship with the CEO: respect for CEO; goal- sharing (r=.782, p<0.01); having a strong relationship (r= .718, p<0.01); co-problem-solving (r=.437, p<0.01); having an interesting job (r=.406, p<0.01); having similar interests with CEO (r= .346, p<0.01); CEO and CNE maintaining specific roles (r= .261, p<0.05); satisfaction with CNE income (r=.251, p<0.05); willingness to improve relationship with CEO (r=.254, p<0.05). CNE positions demonstrated an ethnic diversity factor of 0.03%. CNE replacement costs to healthcare facilities were over 1.5 million dollars.

CONCLUSION: CNE/CEO relationships have identified cohesive factors that may contribute to CNE longevity in position; an ethically diverse CNE deficit exists; and, CNE turnover and vacancy rates impact an organization's financial health and quality of care.

Percutaneous laser disc decompression for thoracic disc disease: report of 10 cases

Scott M.W. Haufe, Anthony R. Mork, Morgan Pyne, Ryan A. Baker — 2010-6-1

Background: Discogenic pain or herniation causing neural impingement of the thoracic vertebrae is less common than that in the cervical or lumbar regions. Treatment of thoracic discogenic pain usually involves conservative measures. If this fails, conventional fusion or discectomy can be considered, but these procedures carry significant risk.

Objectives: To assess the efficacy and safety of percutaneous laser disc decompression (PLDD) for the treatment of thoracic disc disease.

Methods: Ten patients with thoracic discogenic pain who were unresponsive to conservative intervention underwent the PLDD procedure. Thoracic pain was assessed using the Visual Analog Scale (VAS) scores preoperatively and at 6-month intervals with a minimum of 18-months follow-up. Patients were diagnosed and chosen for enrollment based on abnormal MRI findings and positive provocative discograms. Patients with gross herniations were not included.

Results: Length of follow-up ranged from 18 to 31 months (mean: 24.2 mo). Median pretreatment thoracic VAS score was 8.5 (range: 5-10) and median VAS score at final follow-up was 3.8 (range: 0-9). Postoperative improvement was significant with a 99% confidence interval. Of interest, patients generally fell into two groups, those with significant pain reduction and those with little to no improvement. Although complications such as pneumothorax, discitis, or nerve damage were possible, no adverse events occurred during the procedures.

Limitations: The study is limited by its small size and lack of a sham group. Larger controlled studies are warranted.

Conclusions: With further clinical evidence, PLDD could be considered a viable option with a low risk of complication for the treatment of thoracic discogenic pain that does not resolve with conservative treatment.

NITRIC OXIDE (NO), CITRULLINE - NO CYCLE ENZYMES, GLUTAMINE SYNTHETASE AND OXIDATIVE STRESS IN ANOXIA (HYPOBARIC HYPOXIA) AND REPERFUSION IN RAT BRAIN

2010-5-31

Nitric oxide is postulated to be involved in the pathophysiology of neurological disorders due to hypoxia/ anoxia in brain due to increased release of glutamate and activation of N-methyl-D-aspartate receptors. Reactive oxygen species have been implicated in pathophysiology of many neurological disorders and in brain function. To understand their role in anoxia (hypobaric hypoxia) and reperfusion (reoxygenation), the nitric oxide synthase, argininosuccinate synthetase, argininosuccinate lyase, glutamine synthetase and arginase activities along with the concentration of nitrate /nitrite, thiobarbituric acid reactive substances and total antioxidant status were estimated in cerebral cortex, cerebellum and brain stem of rats subjected to anoxia and reperfusion. The results of this study clearly demonstrated the increased production of nitric oxide by increased activity of nitric oxide synthase. The increased activities of argininosuccinate synthetase and argininosuccinate lyase suggest the increased and effective recycling of citrulline to arginine in anoxia, making nitric oxide production more effective and contributing to its toxic effects. The decreased activity of glutamine synthetase may favor the prolonged availability of glutamic acid causing excitotoxicity leading to neuronal damage in anoxia. The increased formation of thiobarbituric acid reactive substances and decreased total antioxidant status indicate the presence of oxidative stress in anoxia and reperfusion. The increased arginase and sustained decrease of GS activity in reperfusion group likely to be protective.

Gain of a 500-fold sensitivity on an intravital MR Contrast Agent based on an endohedral Gadolinium-Cluster-Fullerene-Conjugate: A new chance in cancer diagnostics

2010-5-28

Among the applications of fullerene technology in health sciences the expanding field of magnetic resonance imaging (MRI) of molecular processes is most challenging. Here we present the synthesis and application of a Gd_xSc_3-xN@C₈₀-BioShuttle-conjugate referred to as Gd-cluster@-BioShuttle, which features high proton relaxation and, in comparison to the commonly used contrast agents, high signal enhancement at very low Gd concentrations. This modularly designed contrast agent represents a new tool for improved monitoring and evaluation of interventions at the gene transcription level. Also, a widespread monitoring to track individual cells is possible, as well as sensing of microenvironments. Furthermore, BioShuttle can also deliver constructs for transfection or active pharmaceutical ingredients, and scaffolding for incorporation with the host's body. Using the Gd-cluster@-BioShuttle as MRI contrast agent allows an improved evaluation of radio- or chemotherapy treated tissues.

Evaluation of Lumbar Facet Joint Nerve Blocks in Managing Chronic Low Back Pain: A Randomized, Double-Blind, Controlled Trial with a 2-Year Follow-Up

2010-5-28

Study Design: A randomized, double-blind, controlled trial.

Objective: To determine the clinical effectiveness of therapeutic lumbar facet joint nerve blocks with or without steroids in managing chronic low back pain of facet joint origin.

Summary of Background Data: Lumbar facet joints have been shown as the source of chronic pain in 21% to 41% of low back patients with an average prevalence of 31% utilizing controlled comparative local anesthetic blocks. Intraarticular injections, medial branch blocks, and radiofrequency neurotomy of lumbar facet joint nerves have been described in the alleviation of chronic low back pain of facet joint origin.

Methods: The study included 120 patients with 60 patients in each group with local anesthetic alone or local anesthetic and steroids. The inclusion criteria was based upon a positive response to diagnostic controlled, comparative local anesthetic lumbar facet joint blocks.

Outcome measures included the numeric rating scale (NRS), Oswestry Disability Index (ODI), opioid intake, and work status, at baseline, 3, 6, 12, 18, and 24 months.

Results: Significant improvement with significant pain relief of ≥ 50% and functional improvement of ≥ 40% were observed in 85% in Group 1, and 90% in Group II, at 2-year follow-up.

The patients in the study experienced significant pain relief for 82 to 84 weeks of 104 weeks, requiring approximately 5 to 6 treatments with an average relief of 19 weeks per episode of treatment.

Conclusions: Therapeutic lumbar facet joint nerve blocks, with or without steroids, may provide a management option for chronic function-limiting low back pain of facet joint origin.

Endoscopic Facet Debridement for the treatment of facet arthritic pain - a novel new technique

Scott M.W. Haufe, Anthony R. Mork — 2010-5-25

Study design: Retrospective, observational, open label.

Objective: We investigated the efficacy of facet debridement for the treatment of facet joint pain.

Summary of background data: Facet joint disease, often due to degenerative arthritis, is common cause of chronic back pain. In patients that don't respond to conservative measures, nerve ablation may provide significant improvement. Due to the ability of peripheral nerves to regenerate, ablative techniques of the dorsal nerve roots often provide only temporary relief. In theory, ablation of the nerve end plates in the facet joint capsule should prevent reinnervation.

Methods: All patients treated with endoscopic facet debridement at our clinic from 2003-2007 with at least 3 years follow-up were included in the analysis. Primary outcome measure was percent change in facet-related pain as measured by Visual Analog Scale (VAS) score at final follow-up visit.

Results: A total of 174 people (77 women, 97 men; mean age 64, range 22-89) were included. Location of facet pain was cervical in 45, thoracic in 15, and lumbar in 114 patients. At final follow-up, 77%, 73%, and 68% of patients with cervical, thoracic, or lumbar disease, respectively, showed at least 50% improvement in pain. Mean operating time per joint was 17 minutes (range, 10-42). Mean blood loss was 40 ml (range, 10-100). Complications included suture failure in two patients, requiring reclosure of the incision. No infection or nerve damage beyond what was intended occurred.

Conclusions: Our results demonstrate a comparable efficacy of endoscopic facet debridement compared to radiofrequency ablation of the dorsal nerve branch, with durable results. Large scale, randomized trials are warranted to further evaluate the relative efficacy of this surgical treatment in patients with facet joint disease.

Parvovirus B19 Genotype Specific Amino Acid Substitution in NS1 Reduces the Protein's Cytotoxicity in Culture

Violetta Kivovich, Leona Gilbert, Matti Vuento, Stanley J. Naides — 2010-5-25

A clinical association between idiopathic liver disease and parvovirus B19 infection has been observed. Fulminant liver failure, not associated with other liver-tropic viruses, has been attributed to B19 in numerous reports, suggesting a possible role for B19 components in the extensive hepatocyte cytotoxicity observed in this condition. A recent report by Abe and colleagues (Int J Med Sci. 2007;4:105-9) demonstrated a link between persistent parvovirus B19 genotype I and III infection and fulminant liver failure. The genetic analysis of isolates obtained from these patients demonstrated a conservation of key amino acids in the nonstructural protein 1 (NS1) of the disease-associated genotypes. In this report we examine a conserved residue identified by Abe and colleagues and show that substitution of isoleucine 181 for methionine, as occurs in B19 genotype II, results in the reduction of B19 NS1-induced cytotoxicity of liver cells. Our results support the hypothesis that in the setting of persistent B19 infection, direct B19 NS1-induced cytotoxicity may play a role in idiopathic fulminant liver failure.

Growth of Microorganisms in Total Parenteral Nutrition Solutions Containing Lipid

2010-5-18

Background: To identify the microorganisms that can grow rapidly in total parenteral nutrition (TPN) solutions, we investigated the growth of the major causes of catheter-related blood stream infection (Staphylococcus aureus, Serratia marcescens, Bacillus cereus, and Candida albicans) in TPN solutions containing lipid. Methods: The pH value of a TPN solution containing lipid (pH 6.0, containing 20 ppm of NaHSO₃) was adjusted by the addition of HCl to 5.7, 5.4, or 4.9. The pH value of another TPN solution (pH5.5, containing 400 ppm of NaHSO₃) was adjusted by the addition of NaOH to 5.9, 6.3, or 6.8. A specific number of each microorganism was added to 10 mL of each test solution and incubated at room temperature. The number of microorganisms was counted as colony forming units at 0, 24, and 48 hrs later. Results: C albicans increased similarly at any pH values in the TPN solution. The bacterial species also increased rapidly at pH6.0 in the solution containing 20 ppm of NaHSO₃, but growth was suppressed as the pH value was reduced, with growth halted at pH4.9. However, these bacterial species did not increase, even at pH5.9, in the other solution containing 400 ppm of NaHSO₃. Conclusions: These results suggest that Candida species can grow rapidly in almost all TPN solutions regardless of the acidity, lipid, and NaHSO₃; also, some bacterial species may grow in TPN solutions containing lipid unless the pH value is 5.0 or less. Therefore, each TPN solution should be examined whether or not the bacterial species can proliferate.

Factors affecting the long-term response to tacrolimus in renal transplant patients: Pharmacokinetic and pharmacogenetic approach

2010-5-11

Background: The aim of our study was to determine the impact of CYP3A5*1 and CYP3A5*3 on the kinetics of tacrolimus in renal transplant recipients.

Material and methods: Forty kidney recipients were selected to participate. Maintenance scheme consisted of tacrolimus, a purine inhibitor and a steroid. CYP3A5 genotyping was performed with PCR and RFLP. Pharmacokinetic model was developed with Linear Regression and General Linear Model repeated measures approach. The impact of sex, CYP3A5*1 allele, age at transplantation, hepatic and renal function on tacrolimus kinetics was examined.

Results: The frequency of CYP3A5*3/*3 and CYP3A5*1/*3 genotype was 35/40 and 5/40, respectively. No CYP3A5*1/*1 was detected. CYP3A5*1 variant was associated with significant lower TAC dose adjusted concentration at 3, 6, 12 and 36 months after transplantation. Hepatic and renal function showed a significant effect on tacrolimus dose adjusted concentration 3 months after transplantation (p=0.000 and 0.028, respectively). Sex did not show a significant impact on tacrolimus kinetics. Carriers of CYP3A5*1 allele had lower predicted measures for tacrolimus dose adjusted concentration and higher predicted measures for volume of distribution.

Conclusion: We proved that CYP3A5*1 carriers need higher tacrolimus dose than CYP3A5*3 homozygotes to achieve the target blood concentration.

Serum cholesterol concentration associated with aspirin esterase activity in older people: preliminary data

2010-5-10

OBJECTIVE: Metabolism of aspirin (acetylsalicylic acid), commonly used in older people for the prevention of cardiovascular disease, is important to the effectiveness of this drug. Whereas part of aspirin hydrolysis occurs in blood, there is a paucity of information in regards to circulating aspirin esterase activity in various physiological and pathological conditions. High aspirin esterase activity, corresponding to faster aspirin hydrolysis (thus aspirin non-responsiveness), may occur in cardiovascular disease-prone states. The objective of this study was to investigate the effects of cardio-metabolic variables such as cholesterol on serum aspirin esterase activity in older people who participated in an intervention study on physical activity.

METHODS: A total of 18 non-medicated subjects (7 men/11 women, mean age 67.8 years, body mass index = 23.4 ± 3.3 kg/m²), who completed a 3-month interventional program for a mild-to-moderate increase in physical activity, were analyzed. The body mass index, plasma glucose, serum total cholesterol and aspirin esterase activity were measured in the pre- and post-interventional phases of the study.

RESULTS: During the interventional period, the changes in aspirin esterase activity correlated significantly and positively with those of total cholesterol concentrations (r = 0.542, P = 0.020; β = 0.609, P = 0.035 in a multiple linear regression analysis after adjusting for all the measured variables).

CONCLUSION: The results suggest that cholesterol metabolism alterations may be associated with aspirin metabolism in older people.

Effects of Losartan on expression of connexins at the early stage of atherosclerosis in rabbits

Li-ming Ruan, Wei Cai, Jun-zhu Chen, Jin-feng Duan — 2010-5-8

Aim: to investigate effects of Losartan on expression of connexin 40 and 43 (Cx40 and Cx43), in arteries at the early stage of atherosclerosis in a rabbit model. Methods: A total of 28 male New Zealand white rabbits were divided into following groups: control group, high fat diet group, and Losartan group (10 mg/kg/day). Losartan was administrated in food for two weeks. Iliac arteries were obtained for immunohistochemistry, transmission electron microscopy, Western blot, and reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Transmission electron microscopy revealed abundant gap junctions between neointimal smooth muscle cells (SMCs), which were markedly reduced by treatment. RT-PCR and Western blot assay showed that the mRNA and protein expression of Cx40 and Cx43 were elevated in the neointimal area at the early stage of atherosclerosis. The mRNA and protein expression of Cx43 were significantly down-regulated by losartan treatment but those of Cx40 were not markedly changed. Conclusion: Cx40 and Cx43 in the neointimal SMCs were up-regulated at the early stage of atherosclerosis. Losartan (an angiotensin-converting enzyme inhibitor) could reduce neointima proliferation and down-regulate the elevated protein expression of Cx43, suggesting the rennin-angiotensin system (RAS) plays an important role in the remodeling of gap junction between ventricular myocytes under pathological conditions.

WT1 PEPTIDE VACCINATION IN COMBINATION WITH IMATINIB THERAPY FOR A PATIENT WITH CML IN THE CHRONIC PHASE

2010-4-20

Although tyrosine kinase inhibitors is effective for dramatically reducing CML cells, it might be difficult to eradicate completely the CML stem cells. We aimed to clarify the safety and effects of WT1 peptide vaccination in combination with imatinib therapy for a CML patient. A 51 year-old male with CML in CP, who showed a resistance against imatinib therapy for 2.5 years, began to be treated with 9mer modified-type WT1 peptides in combination with standard dose of imatinib. Although every 2-week-administration of WT1 peptides for 22 weeks did not show definite effects on the quantification of bcr-abl transcripts, by changing the administration from every 2 weeks to 4 weeks bcr-abl transcripts decreased remarkably. After 11 months of every 4-week-administration of the peptides and 12 months post cessation of the peptides bcr-abl transcripts achieved to the level below detection by RQ/RT-PCR (complete molecular response). WT1/MHC tetramer⁺CD8⁺ CTLs, which appeared after the second administration of WT1 peptides and remained more than 15 in number among 10⁶ CD8⁺ T cells throughout the administration of WT1 peptides, are still present in the blood on 14th month post cessation of the peptides. An in vitro study as to the cytotoxicity of lymphocytes induced by mixed lymphocyte peptide culture demonstrated that cultured lymphocytes possessed cytotoxicity against WT1 expressing leukemia cells and the cytotoxicity was WT1-specific and MHC class I restricted. The present study showed that WT1 peptide vaccination in combination with TKI is feasible and effective in the therapy for imatinib-resistant CML.

Godoy & Godoy technique in the treatment of lymphedema for under-privileged populations

José Maria Pereira de Godoy, Maria de Fátima Guerreiro de Godoy — 2010-4-15

The aim of this paper is to report new options in the treatment of lymphedema for under-privileged populations. Several articles and books have been published reporting recent advances and contributions. A new technique of manual lymph drainage, mechanisms of compression, development of active and passive exercising apparatuses and the adaptation of myolymphokinetic activities have been developed for the treatment of lymphedema. This novel approach can be adapted for the treatment of lymphedema in mass.

Autonomic Dysfunction Presenting as Postural Orthostatic Tachycardia Syndrome in Patients with Multiple Sclerosis

Khalil Kanjwal, Beverly Karabin, Yousuf Kanjwal, Blair P Grubb — 2010-3-11

Background: Autonomic dysfunction is common in patients suffering from multiple sclerosis (MS) and orthostatic dizziness occurs in almost 50% of these patients. However, there have been no reports on postural orthostatic tachycardia syndrome (POTS) in patients suffering from MS.

Methods: The patients were included for analysis in this study if they had POTS with either a prior history of MS or having developed MS while being followed for POTS. Postural orthostatic tachycardia (POTS) is defined as symptoms of orthostatic intolerance(>6months) accompanied by a heart rate increase of at least 30 beats/min (or a rate that exceeds 120 beats/min) that occurs in the first 10 minutes of upright posture or head up tilt test (HUTT) occurring in the absence of other chronic debilitating disorders. We identified nine patients with POTS who were suffering from MS as well. Each of these patients had been referred from various other centers for second opinions.

Results: The mean age at the time of diagnosis of POTS was 49±9 years and eight of the 9 patients were women. Five patients (55%) had hyperlipidemia, 3 (33%) migraine and 2 (22%) patients had coronary artery disease and diabetes each. Fatigue and palpitations (on assuming upright posture) were the most common finding in our patients (9/9). All patients also had orthostatic dizziness. Syncope was seen in 5/9(55%) of patients. Four patients (44%), who did not have clear syncope, were having episodes of near syncope. The presence of POTS in our study population resulted in substantial limitation of daily activities. Following recognition and treatment of POTS, 6/9(66%), patients were able to resume daily activities of living. Their symptoms (especially fatigue and orthostatic intolerance) improved. The frequency and severity of syncope also improved. Three (33%) patients failed to show a good response to treatment.

Conclusion: Patients suffering from MS may manifest autonomic dysfunction by developing POTS. Early recognition and proper management may help improve the symptoms of POTS.

Association between regulated upon activation, normal T cells expressed and secreted (RANTES) -28C/G polymorphism and asthma risk - A Meta-Analysis

Qiaoqiao Fang, Furu Wang, Deyu Zhao — 2010-2-10

Regulated upon activation, normal T-cell expressed and secreted (RANTES) is one of the most extensively studied C-C chemokines in allergic inflammation. A growing body of evidence suggests that many cell types present in asthmatic airways have the capacity to generate RANTES, which directly supported the potential role of RANTES in asthma. A number of studies have evaluated the functional polymorphism -28C/G in the RANTES promoter region, which had been found to affect the transcription of the RANTES gene, in relation to asthma susceptibility. However, the results remain conflicting rather than conclusive. This meta-analysis on 1894 asthma cases and 1766 controls for -28C/G from 9 published case-control studies showed that the variant allele -28G was associated with significantly increased risk of asthma (GG+CG vs CC: OR=1.24, 95%CI=1.08-1.41) without any between-study heterogeneity.

In the stratified analysis by asthma type, age and ethnicity, we found that the increased asthma risk associated with -28G/C polymorphism was more evident in children (OR=1.24, 95%CI=1.06-1.45), Asian group (OR=1.27, 95%CI=1.04-1.56) and African group (OR=1.72, 95%CI=1.07-2.78). These results suggest that RANTES -28G/C polymorphism may contribute to asthma development, especially in children and in Asian population. Additional well-designed large studies were required for the validation of this association.

Effect of dose-escalation of 5-fluorouracil on circadian variability of its pharmacokinetics in Japanese patients with Stage III/IVa esophageal squamous cell carcinoma

2010-1-31

Objective: The effects of dose-escalation of 5-fluorouracil (5-FU) on the clinical outcome and pharmacokinetics of 5-FU were investigated in Japanese patients with Stage III/IVa esophageal squamous cell carcinoma.

Methods: Thirty-five patients with Stage III/IVa were enrolled, who were treated with a definitive 5-FU/cisplatin-based chemoradiotherapy. A course consisted of continuous infusion of 5-FU at 400 mg/m²/day (the standard dose group, N=27) or 500-550 mg/m²/day (the high dose group, N=8) for days 1-5 and 8-12, infusion of cisplatin at 40 mg/m²/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. Plasma concentrations of 5-FU were determined by high performance liquid chromatography at 5:00 PM on days 3, 10, 38 and 45, and at 5:00 AM on days 4, 11, 39 and 46.

Results and conclusions: No patient with Stage IVa achieved a complete response in the standard dose group, whereas a complete response was observed at a rate of 50% in the high dose group, and this can be explained by a higher plasma concentration of 5-FU. The circadian rhythm in the concentrations found at the standard dose was not observed for a higher dose.

Growth of Microorganisms in Total Parenteral Nutrition Solutions Without Lipid

Takashi Kuwahara, Shinya Kaneda, Kazuyuki Shimono, Yoshifumi Inoue — 2010-1-22

Background: To identify the microorganisms that can grow rapidly in total parenteral nutrition (TPN) solutions, we investigated the growth of the major causes of catheter-related blood stream infection (Staphylococcus aureus, Serratia marcescens, Bacillus cereus, and Candida albicans) in TPN solutions without lipid. Methods: Experiment 1: A commercial TPN solution without lipid containing multivitamins (pH5.6) was used. A specific number of each test microorganism was added to each 10 mL of the TPN solution and incubated at room temperature. An aliquot of test solution was sampled and inoculated to SCD agar plates at 0, 24, and 48 hrs after the addition of the microorganisms. The number of microorganisms was counted as colony forming units. Experiment 2: The other 2 commercial TPN solutions without lipid (pH5.5) were supplemented with multivitamins. The pH values of the solutions were adjusted to about 6.0, 6.5, or 7.0 using 0.5 mol/L NaOH. The addition of microorganisms, incubation, and counting were performed in the same manner. Results: Experiment 1: S. aureus, S. marcescens, and B. cereus did not increase in the TPN solution without lipid containing multivitamins (pH5.6), but C. albicans increased rapidly. Experiment 2: The 3 bacterial species did not increase even at pH6.0, but increased at pH6.5 and increased rapidly at pH7.0 in both TPN solutions. C. albicans increased similarly at any pH. Conclusion: These results suggest that bacterial species cannot grow in TPN solutions without lipid due to the acidity (pH5.6 or lower), but Candida species can grow regardless of the acidity.

Weight loss, leukopenia and thrombocytopenia associated with sustained virologic response to Hepatitis C treatment

Nuntra Suwantarat, Alan D. Tice, Thana Khawcharoenporn, Dominic C. Chow — 2010-1-22

OBJECTIVE: To identify apparent adverse effects of treatment of chronic hepatitis C and their relationship to sustained virologic response (SVR).

METHODS: A retrospective study was conducted of all Hepatitis C virus (HCV)-infected patients treated with pegylated interferon and ribavirin in an academic ambulatory infectious disease practice. Clinical and laboratory characteristics were compared between patients with SVR and without SVR.

RESULTS: Fifty-four patients completed therapy with the overall SVR rate of 76%. SVR was associated with genotype non-1 (P=0.01), weight loss more than 5 kilograms (P=0.04), end of treatment leukopenia (P=0.02) and thrombocytopenia (P=0.05). In multivariate analysis, SVR was significant associated with HCV genotype non-1 (Adjusted Odd Ratio [AOR] 15.22; CI 1.55 to 149.72; P=0.02), weight loss more than 5 kilograms, (AOR 5.74; CI 1.24 to 26.32; P=0.04), and end of treatment white blood cell count level less than 3 X 10³ cells/µl (AOR 9.09; CI 1.59 to 52.63; P=0.02). Thrombocytopenia was not significant after adjustment. Other factors including age, gender, ethnicity, injection drug use, viral load, anemia, alanine transaminase level, and liver histology did not reach statistical significance.

CONCLUSION: Besides non-1 genotype, SVR was found to be independently associated with weight loss during therapy, and leukopenia at the end of HCV treatment. These correlations suggest continuation of therapy despite adverse effects, may be of benefit.

Ultra-low microcurrent in the management of diabetes mellitus, hypertension and chronic wounds: Report of twelve cases and discussion of mechanism of action

2009-12-6

Oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus and cardiovascular diseases including hypertension. The low levels of antioxidants accompanied by raised levels of markers of free radical damage play a major role in delaying wound healing. Ultra-low microcurrent presumably has an antioxidant effect, and it was shown to accelerate wound healing. The purpose of the study is to investigate the efficacy of ultra-low microcurrent delivered by the Electro Pressure Regeneration Therapy (EPRT) device (EPRT Technologies-USA, Simi Valley, CA) in the management of diabetes, hypertension and chronic wounds. The EPRT device is an electrical device that sends a pulsating stream of electrons in a relatively low concentration throughout the body. The device is noninvasive and delivers electrical currents that mimic the endogenous electric energy of the human body. It is a rechargeable battery-operated device that delivers a direct current (maximum of 3 milliAmperes) of one polarity for 11.5 minutes, which then switched to the opposite polarity for another 11.5 minutes. The resulting cycle time is approximately 23min or 0.000732 Hz and delivers a square wave bipolar current with a voltage ranging from 5V up to a maximum of 40 V. The device produces a current range of 3 mA down to 100 nA. Twelve patients with long standing diabetes, hypertension and unhealed wounds were treated with EPRT. The patients were treated approximately for 3.5 h/day/5 days a week. Assessment of ulcer was based on scale used by National Pressure Ulcer Advisory Panel Consensus Development Conference. Patients were followed-up with daily measurement of blood pressure and blood glucose level, and their requirement for medications was recorded. Treatment continued from 2-4 months according to their response. Results showed that diabetes mellitus and hypertension were well controlled after using this device, and their wounds were markedly healed (30-100%). The patients either reduced their medication or completely stopped after the course of treatment. No side effects were reported. The mechanism of action was discussed.

The Diels-Alder-Reaction with inverse-Electron-Demand, a very efficient versatile Click-Reaction Concept for proper Ligation of variable molecular Partners

2009-12-5

The ligation of active pharmaceutical ingredients (API) for working with image processing systems in diagnostics (MRT) attracts increasing notice and scientific interest. The Diels-Alder ligation Reaction with inverse electron demand (DAR_inv) turns out to be an appropriate candidate. The DAR_inv is characterized by a specific distribution of electrons of the diene and the corresponding dienophile counterpart. Whereas the reactants in the classical Diels-Alder Reaction feature electron-rich diene and electron-poor dienophile compounds, the DAR_inv exhibits exactly the opposite distribution of electrons. Substituents with pushing electrones increase and, with pulling electrons reduce the electron density of the dienes as used in the DAR_inv.

We report here that the DAR_inv is an efficient route for coupling of multifunctional molecules like active peptides, re-formulated drugs or small molecules like the alkyalting agent temozolomide (TMZ). This is an example of our contribution to the "Click chemistry" technology. In this case TMZ is ligated by DAR_inv as a cargo to transporter molecules facilitating the passage across the cell membranes into cells and subsequently into subcellular components like the cell nucleus by using address molecules. With such constructs we achieved high local concentrations at the desired target site of pharmacological action. The DAR_inv ligation was carried out using the combination of several technologies, namely: the organic chemistry and the solid phase peptide synthesis which can produce 'tailored' solutions for questions not solely restricted to the medical diagnostics or therapy, but also result in functionalizations of various surfaces qualified amongst others also for array development.

We like to acquaint you with the DAR_inv and we like to exemplify that all ligation products were generated after a rapid and complete reaction in organic solutions at room temperature, in high purity, but also, hurdles and difficulties on the way to the TMZ-BioShuttle conjugate should be mentioned.

With this report we would like to stimulate scientists working with the focus on "Click chemistry" to intensify research with this expanding DAR_invable to open the door for new solutions inconceivable so far.

Comparison between single antiplatelet therapy and combination of antiplatelet and anticoagulation therapy for secondary prevention in ischemic stroke patients with antiphospholipid syndrome

2009-12-5

Satisfactory results have not yet been obtained in therapy for secondary prevention in ischemic stroke patients with antiphospholipid syndrome (APS). We therefore compared single antiplatelet therapy and a combination of antiplatelet and anticoagulation therapy for secondary prevention in ischemic stroke patients with APS.

The subjects were 20 ischemic stroke patients with antiphospholipid antibody, 13 with primary antiphospholipid syndrome and 7 with SLE-related antiphospholipid syndrome. Diagnosis of APS was based on the 2006 Sydney criteria. Eligible patients were randomly assigned to either single antiplatelet therapy (aspirin 100 mg) or a combination of antiplatelet and anticoagulation therapy (target INR: 2.0-3.0; mean 2.4±0.3) for the secondary prevention of stroke according to a double-blind protocol. There was no significant difference between the two groups in age, gender, NIH Stroke Scale on admission, mRS at discharge, or rate of hypertension, diabetes mellitus, hyperlipidemia, or cardiac disease. We obtained Kaplan-Meier survival curves for each treatment. The primary outcome was the occurrence of stroke. The mean follow-up time was 3.9±2.0 years. The cumulative incidence of stroke in patients with single antiplatelet treatment was statistically significantly higher than that in patients receiving the combination of antiplatelet and anticoagulation therapy (log-rank test, p-value=0.026). The incidence of hemorrhagic complications was similar in the two groups. The recent APASS study did not show any difference in effectiveness for secondary prevention between single antiplatelet (aspirin) and single anticoagulant (warfarin) therapy. Our results indicate that combination therapy may be more effective in APS-related ischemic stroke.

Fat-Storing Multilocular Cells Expressing CCR5 Increase in the Thymus with Advancing Age: Potential Role for CCR5 Ligands on the Differentiation and Migration of Preadipocytes

2009-12-4

Age-associated thymic involution is characterized by decreased thymopoiesis, adipocyte deposition and changes in the expression of various thymic microenvironmental factors. In this work, we characterized the distribution of fat-storing cells within the aging thymus. We found an increase of unilocular adipocytes, ERTR7⁺ and CCR5⁺fat-storing multilocular cells in the thymic septa and parenchymal regions, thus suggesting that mesenchymal cells could be immigrating and differentiating in the aging thymus. We verified that the expression of CCR5 and its ligands, CCL3, CCL4 and CCL5, were increased in the thymus with age. Hypothesizing that the increased expression of chemokines and the CCR5 receptor may play a role in adipocyte recruitment and/or differentiation within the aging thymus, we examined the potential role for CCR5 signaling on adipocyte physiology using 3T3-L1 pre-adipocyte cell line. Increased expression of the adipocyte differentiation markers, PPARγ2 and aP2 in 3T3-L1 cells was observed under treatment with CCR5 ligands. Moreover, 3T3-L1 cells demonstrated an ability to migrate in vitro in response to CCR5 ligands. We believe that the increased presence of fat-storing cells expressing CCR5 within the aging thymus strongly suggests that these cells may be an active component of the thymic stromal cell compartment in the physiology of thymic aging. Moreover, we found that adipocyte differentiation appear to be influenced by the proinflammatory chemokines, CCL3, CCL4 and CCL5.