No abstract

The trace element content of the brain of two patients with Pick's disease examined postmortem was studied using instrumental neutron activation analysis. Results showed significant increases in chlorine, iron, manganese, sodium, and phosphorus and significant decreases in chromium, cesium, rubidium, and selenium and in the mean freeze-dried to wet-weight ratio for patients with Pick's disease compared with control patients. Brain zinc content was not elevated in the two patients, a finding that fails to support the hypothesis that elevated zinc levels play a role in the pathogenesis of Pick's disease.

Instrumental neutron activation analysis procedures were used to determine the aluminum content of various brain regions in histologically verified Alzheimer disease (AD) and in controls. The grand mean aluminum level for 74 AD specimens was 0.372 +/- 0.058 microgram/gm and for 137 adult controls, 0.467 +/- 0.033 microgram/gm, both on a wet weight basis. No difference was found at the bulk sample level between AD and adult controls, corrected for age and sex, or when frontal, temporal, and hippocampal specimens were compared. Control specimens (infancy to 85 years) showed an increase in brain aluminum concentration with age. Comparison of freeze-dried to wet weight ratios of AD and controls revealed a small increase in water content in AD brains.

The effects of ethanol extract of Trigonella foenum-graecum (Fenugreek) seeds on the blood glucose levels in alloxan-induced diabetic rats at different doses (2g/kg, 1g/kg, 0.5g/kg and 0.1g/kg) were studied. The hypoglycemic effect of extract was compared with that of the standard antidiabetic drug (glimepiride, 4mg/kg) single dose. The extract showed significant activity against the diabetic state induced by alloxan but the intensity of hypoglycemic effect varied from dose to dose. The most effective dose recognized was 1g/kg but that is still lower than the standard antidiabetic drug. No acute toxicity was observed for ethanol extract of T. foenum-graecum seed when it was administered orally at high dose level (3 g/kg body weight), which is higher than effective antihyperglycemic dose, and closely observed for 24 hrs for any mortality and next 10 days for any delayed toxic effects on gross behavioral activities. Phytochemical group tests were also accomplished and presence of alkaloids, steroids and carbohydrates were recognized in the extract.

Activation of fibroblasts and their differentiation into myofibroblasts, excessive collagen production and fibrosis occurs in a number of bladder diseases. Similarly, conversion of epithelial cells into mesenchymal cells (EMT) has been shown to increase fibroblasts like cells. TGF-β1 can induce the EMT and the role of TGF-β1-induced EMT during bladder injury leading to fibrosis and possible organ failure is gaining increasing interest. Here we show that EMT and fibrosis in porcine bladder urothelial (UC) cells are Smad dependent. Fresh normal porcine bladder urothelial cells were grown in culture with or without TGF-β1 and EMT markers were assessed. TGF-β1 treatment induced changes in cellular morphology as depicted by a significant decrease in the expression of E-cadherin and corresponding increase in N-cadherin and α-SMA. We knocked down Smad2 and Smad3 by Smad specific siRNA. Downregulation of E-cadherin expression by TGF-β1 was Smad3-dependent, whereas N-cadherin and α-SMA were dependent on both Smad2 and Smad3. Connective tissue growth factor (CTGF/CCN2), matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) has been shown to play important roles in the pathogenesis of fibrosis. Induction of these genes by TGF-β1 was found to be time dependent. Upregulation of CTGF/CCN2 by TGF-β1 was Smad3 dependent; whereas MMP-2 was Smad2 dependent. Smad2 and Smad3 both participated in MMP-9 expression. TGF-β1 reprogrammed mesenchymal fibroblast like cells robustly expressed collagen I and III and these was inhibited by SB-431542, a TGF-β receptor inhibitor. Our results indicate that EMT of porcine bladder UC cells is TGF-β1 dependent and is mediated through Smad2 and Smad3. TGF-β1 may be an important factor in the development of bladder fibrosis via an EMT mechanism. This identifies a potential amenable therapeutic target.

No abstract

No abstract

No abstract