These findings suggest the possibility that changes in both the amount and the distribution of Cx32 may be implicated in human hepatocarcinogenesis.

FK treatment in the immediate reperfusion period improves hepatic microcirculation and confers a significant protective effect on hepatic ischemia-reperfusion injury in the rat.

Tamoxifen is an estrogen receptor (ER) antagonist used as first-line chemotherapy in breast cancer. Recent studies suggest that tamoxifen may be effective not only for ER‑positive but also for ER‑negative cancer cases. The aim of the present study was to investigate the antiproliferative effect of tamoxifen against human non‑melanoma skin cancer cells. Tamoxifen inhibited the proliferation of the skin squamous cell carcinoma (SCC) cell lines A431, DJM‑1 and HSC‑1. A431 cells did not express ER‑α or -β, suggesting that tamoxifen may exert antiproliferative effects on skin SCC cells via a non‑ER‑mediated pathway. Tamoxifen increased the intracellular calcium concentration of skin SCC cells, and this increase in intracellular calcium concentration by calcium ionophore A23187 suppressed the proliferation of skin SCC cells. These data indicate that tamoxifen inhibited the proliferation of human skin SCC cells via increasing intracellular calcium concentration. Voltage-gated calcium channels and non‑selective cation channels are involved in the increase in intracellular calcium concentration induced by tamoxifen. The broad-spectrum protein kinase C (PKC) inhibitor phloretin significantly attenuated the antiproliferative effect of tamoxifen on skin SCC cells. From these data, it may be concluded that tamoxifen inhibits the proliferation of skin SCC cells by induction of extracellular calcium influx via calcium channels in the plasma membrane and by subsequent activation of PKC.

determined to explore the potential association between these variables and the total renal scars, renal function (glomerular filtration rate, GFR), or daily urinary protein excretion. RESULTSThe number of glomeruli was closely correlated with the actual size of glomeruli ( y = 14.783 − 0.052 x, R = 0.782). To a lesser extent, the number of glomeruli was also closely correlated with the size of glomeruli expressed in SD s ( y = 6.264 − 0.832 x, R = 0.630). There was a good correlation between the number of glomeruli and the extent of renal scarring, renal function, or daily urinary protein excretion, although its association with renal function (GFR) was least evident. CONCLUSIONThere was an association between the decrease in the number of glomeruli and glomerular hypertrophy, decreased renal function, or increased proteinuria. A renal biopsy taken from radiographically and macroscopically normal regions can be useful for assessing RN, and the size and number of glomeruli in the specimens might provide an important measure for estimating the prognosis of RN.

ET receptor blocker (TAK-044) and NO donor (FK409) were used to improve the hepatic microcirculation following ischemia-reperfusion injury. In the first experiment (60 minutes of ischemia), 15 dogs were divided into three groups: group A (control), saline; group B, TAK 5 mg/kg; and group C, FK 0.4 mg/kg. In the second experiment (90 minutes of ischemia), 38 dogs were divided into six groups that underwent 90 minutes of hepatic ischemia followed by reperfusion: group I (control), saline only; group II, TAK 5 mg/kg and FK 3.2 mg/kg; group III, TAK 5 mg/kg and FK 0.4 mg/kg; group IV, TAK 5 mg/kg; group V, FK 0.4 mg/kg; and group VI, FK3.2 mg/kg. All drugs were administered through the portal vein. Following 60 minutes of ischemia, both FK and TAK produced significant improvement in hepatic microcirculation and enzymatic status when compared with the control group. After 90 minutes of ischemia, low doses of FK and TAK significantly improved hepatic microcirculation and reduced portal pressure following reperfusion in group III compared with group I. Leakage of hepatic enzymes was prevented and tissue injury score was significantly lower in group III. In group VI, early protection was obtained to some extent; however, blood pressure was reduced significantly following reperfusion compared with group I. In contrast, hepatocellular function deteriorated and the tissue injury score was higher in group II animals. TAK pretreatment with low doses of FK provided the best protection for the hepatic microcirculation in ischemiareperfusion injury of the liver. (HEPATOLOGY 1998;28:782-788.)Reperfusion injury is an inevitable consequence of ischemia, produced iatrogenically during liver resection or organ preservation before transplantation surgery or as a disease process, such as after prolonged hypotensive shock. Little is known about the mechanism(s) of the injury, but the microcirculatory disturbance is central. 1,2 Microcirculatory disturbance involves two distinct mechanisms: ''no-reflow'' and ''reflow-paradox.'' The no-reflow phenomenon is the consequence of irreversible damage to the nutritive capillary endothelium following prolonged ischemia, whereas the reflow-paradox occurs after any length of ischemia and is carried out by leukocyte-endothelium interaction and release of toxic products including superoxide radicals from the ischemic tissue. Therefore, the length of ischemia (60 minutes or 90 minutes) might be crucial in determining the extent of microvascular injury in hepatic reperfusion injury.Recently, two major breakthroughs revealed the involvement of endothelin (ET) and nitric oxide (NO) in modulating hepatic blood flow after ethanol-and endotoxin-induced liver injury. 3,4 Ischemia led to release of ET, a potent vasoconstrictor, and also externalized the ET receptors in ischemic organs. [5][6][7] In experimental models, inhibition of the effect of ET during ischemia by anti-ET antibody or ET receptor blocker improved microcirculation and circumvented reperfusion injury of the liver. [8][9][10][11] However, us...

Glomerular damage due to either reflux nephropathy or dysplasia may cause proteinuria. Proteinuria of 100 mg/day was significantly (p < 0.01) associated with 2 SD of glomerular hypertrophy on histology and clinical observation (suggesting hyperfiltration). Thereafter, a rapid increase in proteinuria followed by diastolic hypertension appears be significant for predicting ESRD.

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