The effect of local chemical sympathectomy of the rat uterus on its sensitivity to sex hormones

Chemical sympathectomy of the rat uterus did not alter the main metabolic processes maintaining the uterus weight even though it changed its response to sex steroids. Sensitivity of endo- and myometrium to progesterone significantly decreased thus inducing a relative increase in the estradiol action.     

Malignant hepatic tumours associated with previous exposure to Thorotrast: four cases

This report concerns four patients in a district general hospital who died from malignant liver tumours associated with Thorotrast (thorium dioxide) deposits in the liver. Three were known to have had diagnostic angiographic studies performed 36 to 43 years previously using Thorotrast as the contrast agent. In the fourth case no previous relevant information could be obtained. There were two men and one woman with hepatocellular carcinoma and one woman with cholangiocarcinoma. In one of the hepatoma cases there was associated hypercalcaemia of malignancy. Reported latency intervals suggest that cases of Thorotrast-related hepatic malignancy may present up to the second decade of the twenty-first century.     

Interferon (IFN)-alpha activation of human blood mononuclear cells in vitro and in vivo for nitric oxide synthase (NOS) type 2 mRNA and protein expression: possible relationship of induced NOS2 to the anti-hepatitis C effects of IFN-alpha in vivo

Although researchers have noted high level activation of rodent mononuclear phagocytes for nitric oxide (NO) synthase type 2 (S2) expression and NO production with a variety of agents such as interferon (IFN) gamma and endotoxin, it has been difficult to demonstrate activation of human mononuclear phagocytes. The purpose of this study was to determine if IFN-alpha serves as an activator in vitro and in vivo in humans. Treatment of normal monocytes or mononuclear cells in vitro with IFN-alpha caused a dose-dependent increase in monocyte NOS2 activity and NO production, and increased expression of NOS2 protein and mRNA expression. To determine if in vivo administration of IFN-alpha also modulated NOS2, we studied blood cells from patients with hepatitis C before and after IFN-alpha therapy. Untreated patients with chronic hepatitis C virus infection had levels of NOS activity and NOS2 antigen in freshly isolated mononuclear cells similar to those of healthy subjects, and they expressed minimal or no NOS2 mRNA. However, IFN-alpha treatment of patients with hepatitis C infection was associated with a significant elevation in mononuclear cell NOS activity, NOS2 antigen content, and NOS2 mRNA content. IFN-alpha-treated patients had significant decreases in levels of serum alanine aminotransferase and plasma hepatitis C mRNA. The degree of IFN-alpha-enhanced mononuclear cell NOS2 antigen content correlated significantly with the degree of reduction in serum alanine aminotransferase levels. Thus, IFN-alpha treatment of cells in vitro or administration of IFN-alpha to hepatitis C patients in vivo increases expression of mononuclear cell NOS2 mRNA expression, NOS activity, NOS2 antigen expression, and NO production. Since NO has been reported to have antiviral activity for a variety of viruses, we speculate that induced NO production may be related to the antiviral action(s) of IFN-alpha in hepatitis C infection.     

Regional distribution of dopamine D4 receptors in rat forebrain

Binding of the D2-like (D2/D3/D4) radioligand [3H]nemonapride under selective conditions (with 300 nM S[-]-raclopride and other masking agents to occlude D2/D3 receptors and non-specific binding sites) revealed a subset of raclopride-insensitive binding sites considered D4-like receptors. These sites were stereoselective to R(-)-N-n-propylnorapomorphine (NPA) over its S(+)-NPA in a similar fashion to cloned D4 receptors expressed in cell lines. In addition, the highly D4-selective agent L-745,870 displaced 74-83% of these sites in rat brain regions, suggesting that most were D4 receptors. These apparent D4 receptors represented a relatively high proportion of D2-like receptors in hippocampus, dorsolateral frontal, medial prefrontal and entorhinal cortex, but fewer in caudate-putamen and nucleus accumbens.