Diverse functions of the p75 neurotrophin receptor

The pan-neurotrophin receptor p75NTR belongs to a large family of receptors, which includes tumor necrosis factor receptors, Fas and approximately 25 other members. The p75NTR is the first receptor to be cloned molecularly. Recent years have seen the emergence of a consensus regarding the signaling pathways activated by p75NTR and its potential biological function, although receptor characterization had not been targeted for some years. We now know that p75NTR has surprisingly diverse effects, ranging from cell death to regulation of axon elongation. This diversity can be explained by the complex formation of p75NTR with other receptors and multiple signaling molecules that interact with the intracellular domain of p75NTR.     

Carbohydrate metabolism of rats with biliary obstruction

Carbohydrate metabolism of rats with obstructive jaundice caused by bile duct ligation was studied by intravenous glucose tolerance test (IVGTT) and by liver perfusion. The altered levels of carbohydrate-metabolizing enzyme were examined in relation to the glucose metabolism of the cholestatic rats. In the IVGTT, the rate of fractional glucose removal was increased with increases in plasma insulin and glucagon and with a decrease in non-esterified fatty acid. In liver perfusion, neither the glucose uptake nor insulin extraction by the whole liver of icteric rats was different from the control. The increased rate of glucose removal in IVGTT may be due to enhanced glucose utilization by peripheral tissues resulting from hypersecretion of insulin. In liver perfusate supplemented with glucose, a decrease in the glucose uptake per unit liver weight was observed in relation to the lowered glucokinase activity. Formation of glycogen from glucose and of glucose from lactate was also impaired, indicating inhibition of the gluconeogenic system or relative hyperfunction of the glycolytic system, which may further contribute to the reduction in glycogen content. These metabolic disorders correlated well with the changes in activities of key carbohydrate-metabolizing enzymes, which showed a characteristic pattern consistent with the loss of differentiated hepatic functions. Uptake of glucose and its conversion to glycogen were reduced in the cholestatic liver in close association with altered activities of some of related enzymes. However, due to increased utilization by the peripheral tissues, the total amount of glucose utilized in the whole rat was not reduced.     

Antioxidant effect of zinc on acute renal failure induced by ischemia-reperfusion injury in rats

Zinc may have an antioxidant effect mediated by induction of metallothionein. Based on the assumption that metallothionein can scavenge oxygen free radicals, we examined whether zinc administration prior to renal ischemia would improve renal dysfunction caused by ischemia-reperfusion injury in rats. Wistar rats weighing 265 g were treated with an intraperitoneal injection of 20 mg/kg zinc 24 h prior to the renal ischemia-reperfusion procedure, which was achieved by a 30-min clamping of the bilateral renal vessels and subsequent 90-min reperfusion. Thirty-minute renal clearance tests were performed before and after renal ischemia in zinc- (n = 11) and saline-treated (n = 8) rats. Thiobarbituric acid reactive substance, conjugated diene, and metallothionein levels in the renal tissues were also determined. Sham-operated rats (n = 5 in each treatment) served as control for the ischemia-reperfusion rats. Ischemia-reperfusion resulted in significantly lower glomerular filtration rate values and marked increases in tissue concentrations of thiobarbituric acid reactive substance and conjugated diene compared with sham-operation. Zinc administration improved the reduced glomerular filtration rate values seen after the ischemia-reperfusion procedure, but not to the extent of pre-ischemic levels. Zinc pretreatment significantly reduced the increased levels of thiobarbituric acid reactive substance and conjugated diene during ischemia-reperfusion and increased metallothionein levels compared with saline injection. These findings suggest that zinc has an antioxidant effect mediated through the induction of metallothionein, but appears only to have a minor protective effect on renal function induced by renal ischemia-reperfusion injury. Copyright Copyright 1999 S. Karger AG, Basel     

Changes of enzyme activity levels in red blood cells in hemodialysis patients by recombinant human erythropoietin.

In a phase II clinical trial to test the ability of recombinant human erythropoietin (r-HuEPO) to reverse the anemia of patients undergoing hemodialysis, the changes of enzyme activity in red blood cells were evaluated in 5 hemodialysis anemic patients who were treated with r-HuEPO. Concerning the activity levels measured, the following conclusions are drawn. 1) HK, ALD, TPI, G6PD and 6PGD were statistically significantly increased at the time when the hematocrit has risen by 8% with the use of r-HuEPO. 2) The enzyme activity levels of PFK, GA3PD, MPGM, ENOL, PK, GR and ADA were higher than normal already before the r-HuEPO treatment. 3) The increases of HK and G6PD by r-HuEPO, as age dependent enzymes, may reflect the generation of young red blood cells. 4) In view of the fact that they are related to ATP production in the glycolysis cycle, we infer that increases of red blood cell enzymes by r-HuEPO may play at least some part in bringing a sensation of "well-being" to severely anemic patients undergoing hemodialysis.     

Long-lasting renal dysfunction following tacrolimus induction therapy in ulcerative colitis patients

Although tacrolimus (TAC) has remarkable effects in ulcerative colitis (UC) patients when given as remission induction therapy, some can develop renal dysfunction during TAC administration, resulting in withdrawal, though related details remain poorly understood. This study was conducted to determine the impact of oral TAC on renal function for remission induction therapy in UC patients. Fifty-five patients (10 elderly, 45 non-elderly) with UC and treated with oral TAC at our hospital were retrospectively evaluated. Renal function was assessed using estimated glomerular filtration rate (eGFR). Although a high clinical response to TAC was seen in both elderly and non-elderly, a decline in eGFR was noted in nearly all patients regardless of age, with a maximum change of −34.4% from the baseline value at week 11. Furthermore, eGFR decline recovered quickly after TAC discontinuation, though did not return to the baseline at two years following cessation. The rate of eGFR change at week 12 was significantly associated with patient age (β = −0.3242, p = 0.0103) and peak serum trough level during TAC treatment (β = 0.3563, p = 0.0051). Furthermore, the rate of decline in eGFR was significantly greater during treatment with TAC in the elderly as compared to non-elderly, with a large difference in eGFR decline rate between those groups also noted at two years after withdrawal of treatment. Careful attention to renal function when administering oral TAC for UC is important and changes in eGFR should be monitored closely in elderly patients even after treatment cessation.     

Label‐free multiphoton excitation imaging as a promising diagnostic tool for breast cancer

Histopathological diagnosis is the ultimate method of attaining the final diagnosis; however, the observation range is limited to the two‐dimensional plane, and it requires thin slicing of the tissue, which limits diagnostic information. To seek solutions for these problems, we proposed a novel imaging‐based histopathological examination. We used the multiphoton excitation microscopy (MPM) technique to establish a method for visualizing unfixed/unstained human breast tissues. Under near‐infrared ray excitation, fresh human breast tissues emitted fluorescent signals with three major peaks, which enabled visualizing the breast tissue morphology without any fixation or dye staining. Our study using human breast tissue samples from 32 patients indicated that experienced pathologists can estimate normal or cancerous lesions using only these MPM images with a kappa coefficient of 1.0. Moreover, we developed an image classification algorithm with artificial intelligence that enabled us to automatically define cancer cells in small areas with a high sensitivity of ≥0.942. Taken together, label‐free MPM imaging is a promising method for the real‐time automatic diagnosis of breast cancer.