Myofibroblasts and the progression of diabetic nephropathy

Background. The cellular mediators of progressive renal fibrosis in diabetic nephropathy remain unknown. Myofibroblasts have been implicated in the pathogenesis of experimental and clinical renal fibrosis. Their role in the progression of diabetic nephropathy is the subject of this study.Subjects and methods. We have studied by immunohistochemistry the expression of cytoskeletal proteins associated with the activation of myofibroblasts; &agr;-smooth-muscle actin (&agr;-SMA), vimentin (Vi) and desmin (D), in the kidneys of 25 patients with diabetic nephropathy (5 patients with diabetic nephropathy (5 patients had a superimposed glomerulonephritis). Comparisons were made with normal tissue for three kidneys removed for renal-cell carcinoma. Correlations were studied between clinical and biochemical parameters with the expression renal cytoskeletal proteins. Results. In normal kidneys, cells expressing &agr;-SMA were confined to the vascular media and adventia while immunoreactive Vi was detected in glomerular epithelial cells. In diabetic kidneys, cells expressing &agr;-SMA were detected primarily in the renal interstitium and to a lesser extent in some glomeruli in association with mesangial proliferation. Vimentin immunostain decreased in glomeruli displaying diabetic hyalinosis and sclerosis. By contrast, strong Vi immunoreactivity was noted in atrophic diabetic tubules and to a lesser extent in the interstitium. Desmin was not detected in either normal or diabetic kidneys. Close correlations were observed between the expression of renal cytoskeletal proteins and the progression of renal insufficiency. Interstitial &agr;-SMA proved to be a predictor of progressive diabetic nephropathy (R² for 1/serum Cr slope=0.608, P=0.00001). This predictive parameters; tubular atrophy (R²=0.477, P=0.00004) and interstitial fibrosis (R²=0.28, P=0.001). Conclusion. We have demonstrated in this study the neoexpression of cytoskeletal proteins within diabetic kidneys. This has allowed the identification of new predicting histological markers for the progression of diabetic nephropathy.     

Antiviral and antioxidant activity of flavonoids and proanthocyanidins from Crataegus sinaica

The antiviral and antioxidant activity of some fractions and of a series of flavonoids and proanthocyanidins obtained from Crataegus sinaica (Rosaceae) was evaluated. The O-glycosidic flavonoids and the oligomeric proanthocyanidins exhibited significant inhibitory activity against herpes simplex virus type 1 (HSV-1), which was shown to be due to an extracellular mechanism for procyanidin C-1. Procyanidin C-1 also had the highest antioxidant activity in both the microsomal lipid peroxidation and the hydroxyl radical scavenging assay. In addition to the previously reported phenolic compounds, the pentacyclic triterpenoid ursolic acid (1) and a tetrameric (2) and pentameric procyanidin (3) are reported for the first time.     

Enterocutaneous Fistula: a Rare Complication of Laparoscopic Adjustable Gastric Banding

Morbid obesity is a refractory disease with serious co-morbidities. Laparoscopic adjustable gastric banding (LAGB) has generally been a safe and effective method for achieving sustained weight loss. We report a man who presented after LAGB with persistent wound infection at the access port-site, which failed conservative management. Diagnostic laparoscopy found an enterocutaneous fistula from herniated bowel (in a Richter's hernia) into which the catheter had eroded. The small bowel and fascial defect were repaired. The catheter was then clipped and divided, and the port was removed.     

Polystyrene/Montmorillonite Nanocomposites Prepared by In Situ Intercalative Polymerization: Influence of the Surfactant Type

Summary: Na‐montmorillonite (MMT) with a cation exchange capacity (CEC) of 90 meq/100 g was converted to MMT‐CTAB and MMT‐CPC by the intercalation of cetyltrimethylammonium bromide (CTAB) and cetylpyridinium chloride (CPC), respectively. The intercalation of CPC onto the basal space of the montmorillonite expanded the basal space from 12.19 to 21.47 Å, whereas in the case of CTAB, the spacing was only expanded to 19.35 Å. The MMT‐CPC and MMT‐CTAB forms were subsequently used as hosts for the preparation of polystyrene nanocomposites via intercalative free‐radical polymerization of styrene. Different structures were obtained by varying the preparation conditions; the exfoliated and intercalated nanocomposites were characterized by X‐ray diffraction (XRD), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), and differential scanning calorimeter (DSC). The produced nanocomposites exhibited improved thermal stability in comparison with that of pure polystyrene above 400 °C especially in the case of the nanocomposites based on the MMT‐CPC, in which intercalation exists. A glass transition temperature (T_g) could not be detected for the prepared nanocomposites using DSC; this was assumed to result from the restricted molecular motion of the polymer chains.

XRD pattern of PS nanocomposites prepared by intercalative polymerization.     

Gender assignment in female congenital adrenal hyperplasia: a difficult experience

OBJECTIVE: To report experience of gender (re)assignment in genotypic female (46XX) patients with congenital adrenal hyperplasia (f-CAH), a difficult and stressful experience if complicated with delayed presentation and inadvertent assignment. PATIENTS AND METHODS: Between 1983 and 2002, 70 patients with f-CAH were counselled for gender assignment. The age at diagnosis and operation, the degree of virilization, parental consanguinity, the gender preference of the families, and the factors governing the decision-making process were determined. RESULTS: Forty-one (59%) patients presented after the neonatal period. All parents had already assumed or were advised of a gender for their children, based on the suggestive appearance of the external genitalia. Consequently, 49 patients were reared as female and 21 as "male". Only nine of these "males" could be reassigned as females (mean age at presentation 7.87 months, sd 10.42). Twelve children had to be reared as "male"(mean age at presentation 55.8 months, sd 32.42) in compliance with the parents' and the study group's decision, and appropriate masculinizing reconstructive surgery was undertaken. The difference in the mean age of those reassigned as female and those who remained "male" was significant (P < 0.001). The parental consanguinity rate among the families was especially high in the 'male' patients. CONCLUSIONS It is extremely difficult to correct the gender of patients with f-CAH when they present at >2.5 years old. Furthermore, the delay in diagnosis and the male bias in choice of gender in our population might be a result of strong social pressures on families, influenced by cultural, traditional and economic factors.     

Influence of Common and Specific HLA-DRB1/DQB1 Haplotypes on Genetic Susceptibilities of Three Distinct Arab Populations to Type 1 Diabetes

The contribution of HLA DRB-DQB to type 1 diabetes (T1D) in Bahrainis, Lebanese, and Tunisians was investigated. DRB1*030101-DQB1*0201 was a locus that conferred susceptibility in three populations, while DRB1*040101-DQB1*0302 was a locus that conferred susceptibility only in Tunisians and Bahrainis. The DRB1*100101-DQB1*050101 (Bahrainis) and DRB1*150101-DQB1*060101 (Lebanese) loci were largely protective. The contribution of HLA to T1D must be evaluated with regard to ethnic background.     

Vitamin K dependent coagulation proteins in endemic hepatosplenomegaly in Egypt.

AIMS--To evaluate the role of bilharzial hepatic fibrosis--whether pure or combined with chronic hepatitis B virus infection--on the functional activity of vitamin K dependent coagulation proteins. METHODS--Coagulation screening using prothrombin time (PT), partial thromboplastin time (PTT), and thrombin time (TT) was carried out on 31 patients with endemic Egyptian hepatosplenomegaly and on 14 healthy controls. The functional activities of factors II, VII, IX and X and protein C were measured. Patients were classified as pure hepatosplenic schistosomiasis (n = 17) and schistosomiasis with concomitant chronic hepatitis B virus infection (n = 14). RESULTS--Prolongation of the PT and PTT were noticed in bilharzial patients compared with the controls. The increase in the TT remained within the upper range of normal. Factors II, VII, IX and X and protein C functional activities were significantly reduced in all groups studied. CONCLUSION--The decreased activity of vitamin K dependent coagulation factors might be partially offset by the reduced activity of circulating protein C which tends to establish a haemostatic balance at a lower level in endemic Egyptian hepatosplenomegaly. No significant difference could be shown between the pure and mixed cases. Schistosomal coagulopathy is therefore not necessarily aggravated by chronic hepatitis B virus infection.     

Modulation of type 1 diabetes susceptibility by tumor necrosis factor alpha -308 G/A and lymphotoxin alpha +249 A/G haplotypes and lack of linkage disequilibrium with predisposing DQB1-DRB1 haplotypes in Bahraini patients

Tumor necrosis factor alpha (TNF-α) −308 G/A and lymphotoxin alpha (LTα) +249 A/G single-nucleotide polymorphisms were investigated in 228 type 1 diabetes mellitus (T1DM) patients and 240 controls. Only LTα +249G allele and +249G/+249G genotype frequencies were higher among patients, and no linkage disequilibrium was found between TNF-α/LTα alleles and susceptible/protective DRB1-DQB1 haplotypes. TNF-α/LTα T1DM-susceptible (−308G/+249G) and protective (−308G/+249A) haplotypes were identified.