糖尿病肾病患者血清TRPM7、Sirtuin-1与钙磷代谢、颈动脉钙化的相关性

目的 探讨糖尿病肾病（DN）患者血清瞬时受体电位通道7(TRPM7)、沉默调节蛋白-1(Sirtuin-1)与钙磷代谢、颈动脉钙化的相关性。方法 选取2020年12月—2022年11月成都大学附属医院收治的97例DN患者作为DN组,另取同期在该院就诊的120例2型糖尿病患者作为对照组。采用实时荧光定量聚合酶链反应检测血清TRPM7的表达,酶联免疫吸附试验检测血清Sirtuin-1水平。采用Pearson法分析DN患者血清TRPM7、Sirtuin-1水平与钙磷代谢的相关性,并通过多因素Logistic逐步回归模型分析DN患者颈动脉钙化的危险因素。结果 DN组血肌酐、尿素氮、血清TRPM7、血磷、颈动脉钙化率高于对照组（P <0.05）。DN组Sirtuin-1、血钙低于对照组（P <0.05）。Pearson相关性分析结果显示,DN患者血清TRPM7与血钙呈负相关（r=-0.247,P=0.000）,与血磷呈正相关（r=0.415,P=0.000）;DN患者血清Sirtuin-1与血钙呈正相关（r=0.367,P=0.000）,与血磷呈负相关（r=-0.505,P=0.00...     

Changes in ultrastructure of hepatocytes and liver test results before,during, and after treatment with interferon-β in patients with HBeAg-positive chronic active hepatitis

We studied the histological and ultrastructural changes in the liver and alterations in the liver test results before, during, and after treatment with human interferon- from five patients with hepatitis B e antigen-positive chronic active hepatitis. A daily dose of 3×10⁶ to 6×10⁶ units of interferon- was given intravenously for four weeks. The total index of periportal and portal inflammation, intralobular degeneration, and focal necrosis before treatment was decreased significantly six months after treatment (P<0.05). Ultrastructurally, the structure of endoplasmic reticulum was irregularly shaped or fragmentally decreased during treatment, but these disappeared six or 12 months after treatment. Glycogen particles diminished greatly during treatment. The alanine aminotransferase concentrations in these patients increased during treatment. Serum albumin and cholinesterase levels decreased significantly at the fourth week of treatment (P<0.01) and at the third day (P<0.01) to the second week (P<0.05) of treatment, respectively. These results suggest that interferon- injures endoplasmic reticulum and glycogen areas and damages the cholinesterase activity in the early stage of treatment and protein synthesis in patients with hepatitis B e antigen-positive chronic active hepatitis.     

The sodium channels of the neuroblastoma x glioma 108 CC 15 hybrid cell change their sensitivity for volatile and local anesthetics upon continuous passage

Summary We have studied the ion flux through the sodium channels of low passage number (<50p.) and high passage number (>150p.) neuroblastoma x glioma hybrid cells using [¹⁴C] guanidinium and specific neurotoxins to induce channel opening and closing. The sodium channels of low passage number hybrid cells could be opened by veratridine alone, suggesting the presence of voltage dependent channels in agreement with electrophysiological studies reported in the literature. The sodium channels of the high passage number hybrid cells, however, needed the synergistic action of veratridine and scorpion toxin for activation suggesting that these channels are silent. The [¹⁴C] guanidinium ion flux through the sodium channels of the high passage number hybrid cells was inhibited by significantly lower concentrations of the volatile anesthetics (halothane, isoflurane and enflurane) and the lcoal anesthetics (tetracaine and bupivacaine) than the comparable flux through the sodium channels of the low passage number hybrid cells.Dedicated to Prof. Dr. E. Wecker on the occasion of his 65th birthday.     

Hepatic,intestinal and renal transport of 1-naphthol-β-d-glucuronide in mutant rats with hereditary-conjugated hyperbilirubinemia

Summary Recently, a mutant rat strain was described with a genetic defect for the biliary excretion of organic anions (TR^– rats). To determine the possible heterogeneity of the transport systems in liver, intestine and kidney we investigated the transport of the anion 1-naphthol--d-glucuronide (1-NG) in isolated vascularly perfused organ preparations of the rat liver, intestine and kidney of both Wistar rats and TR^– rats. 1-NG was administered as such (liver and kidney experiments) or formed intracellularly from 1-naphthol (1-N) (liver and gut experiments). Independent of the type of exposure to 1-NG, the biliary excretion was considerably impaired in TR^– rats. In the intestine the total appearance and the vascular/luminal distribution pattern of 1-NG were not significantly different from the values in control rats. Furthermore, no significant disturbance was found with respect to the renal clearance of 1-NG in the TR^– rat when compared with the Wistar rat. Thus, the genetic defect in the TR^– rat is restricted to an impaired hepatobiliary excretion of 1-NG and does not affect the excretory systems of the intestine and kidney. These results suggest that the excretion of 1-NG by the liver, intestine and kidney involves distinct organ-specific transport systems.     

Involvement of adenylate cyclase and protein kinase C in the α2-adrenoceptor-mediated inhibition of noradrenaline and 5-hydroxytryptamine release in rat hypothalamic slices

Summary In superfused rat hypothalamic slices prelabelled with [³H]-noradrenaline, the ₂-adrenoceptor agonist UK 14304 inhibited in a concentration-dependent manner the electrically-evoked release of tritium. This inhibition was antagonized by the ₂-adrenoceptor blocking agent idazoxan, which by itself increased the electrically-evoked tritium overflow. Exposure to forskolin, an adenylate cyclase activator, increased the electrically-evoked release of [³H]-noradrenaline. In the presence of forskolin (1 mol/l), both the inhibitory effect of UK 14304 and the increasing effect of idazoxan on the electrically-evoked release of [³H]-noradrenaline were less pronounced than in the absence of the adenylate cyclase activator. Exposure to forskolin and to the phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine shifted to the right the concentration-effect curve for UK 14304 in a similar manner as that observed in the presence of forskolin alone. Exposure to phorbol-12,13-dibutyrate (0.01–10 mol/l), a drug which activates protein kinase C, increased the electrically-evoked release of [³H]-noradrenaline. In the presence of phorbol-12,13-dibutyrate (0.1 and 1 mol/l), the concentration effect curve for UK 14304 on tritium overflow was significantly shifted to the right. The increasing effect of idazoxan on tritium overflow was significantly less pronounced in the presence of 1 mol/l phorbol-12,13-dibutyrate.In superfused rat hypothalamic slices prelabelled with [³H]-5-hydroxytryptamine, the ₂-adrenoceptor agonist UK 14304 significantly inhibited the electrically-evoked release of tritium. Exposure to forskolin increased in a concentration-dependent manner [³H]-5-hydroxytryptamine overflow, but did not modify the UK 14304-mediated inhibition. Exposure to 3-isobutyl-1-methylxanthine enhanced the electrically-evoked release of [³H]-5-hydroxytryptamine. In the presence of both forskolin (1 mol/l) and 3-isobutyl-l-methylxanthine (1 mmol/l), the concentration-response curve for UK 14304 was significantly shifted to the right. Exposure to phorbol-12,13-dibutyrate (0.01–10 mol/l) enhanced in a concentration-dependent manner the electrically-evoked overflow of [³H]-5-hydroxytryptamine. In the presence of phorbol-12,13-dibutyrate (0.1 and 1 mol/l), UK 14304 was significantly less potent to inhibit tritium release than in the absence of the protein kinase C activator.It is concluded that both cyclic AMP and phosphoinositide turnover are involved in the modulation of noradrenaline and 5-hydroxytryptamine release by presynaptic ₂-adrenoceptors in rat hypothalamic slices. However, these interactions do not represent definitive proof for a cause-effect relationship for the second messengers mediating the ₂-adrenoceptor induced inhibition of transmitter release either as autoreceptor or as heteroreceptor.Send offprint requests to S. Z. Langer at the above address     

Behavioural effects of selective μ-, κ-, and δ-opioid agonists in neonatal rats

The behavioural effects of selective -, - and -opioid agonists in 5-, 10- and 20-day-old rats were investigated by observational analysis. The predominant response to -agonists was behavioural depression. High doses (10 mg/kg IP) of morphine and DAGO (d-Ala², NMe-Phe⁴, Glyol⁵-enkephalin) produced overt sedation in all the age groups and also induced catalepsy which was particularly apparent in the 5- and 10-day-old animals. These compounds did not produce any signs of behavioural activation in the neonatal rats. In contrast, rat pups treated with the -agonists U50,488H and PD 117,302 (1,10 mg/kg IP) exhibited marked hyperactivity with increases in wall-climbing and locomotion. Sedative effects of the highest dose of the -agonists began to emerge, however, as the animals grew older, resulting in significant decreases in behaviours such as gnawing and grooming at 20 days of age. The -agonist (+)-tifluadom (0.1–10 mg/kg), but not its corresponding (-)-isomer, produced an increase in activity in 5-day-old rats, thus extending the observations made with U50,488H and PD 117,302 and establishing the stereoselective nature of the response. The involvement of -receptors in opioid-induced hyperactivity was further substantiated by using a variety of opioid antagonists. In this context, the increase in activity induced by U50,488H (10 mg/kg) in 5-day-old neonates was attenuated by naltrexone (1 mg/kg IP) but not by larger doses (10 mg/kg) of either M8008 (which has low affinity for -receptors) or the selective -receptor antagonist ICI 174,864. Finally, DPDPE (d-Pen², d-Pen⁵-enkephalin) which acts selectively at -opioid receptors, did not exert any behavioural effects in either the 5-, 10- or 20-day-old rat pups at doses of up to 10 mg/kg. These results demonstrate behavioural effects of - and -but not -agonists in neonatal rats. There is a clear differentiation between - and -receptor effects and both - and -mediated behaviours show dissimilarities from the adult profile.     

Drug Binding to α1-Acid Glycoprotein Studied by Circular Dichroism

The interactions of acidic and basic drugs with ₁-acid glycoprotein (₁-AGP) were investigated using circular dichroism (CD) measurements. Extrinsic Cotton effects were generated by the binding of drugs to ₁-AGP. The CD data suggested the presence of a single binding site on the ₁-AGP molecule. The induced ellipticities of the acidic drug–₁-AGP system decreased with increasing pH, while the ellipticities for the basic drugs increased with pH. The ellipticities for all drugs were reduced by the addition of fatty acids. Furthermore, the induced ellipticities decreased in the presence of cesium chloride for basic drugs bound to ₁-AGP. The extrinsic Cotton effects therefore appear to result from hydrophobic interaction with ₁-AGP for the acidic drugs and from hydrophobic and electrostatic interactions for the basic drugs.     

Distribution and phenotype of murine rotavirus-specific B cells induced by intranasal immunization with 2/6 virus-like particles

Virus-like particles containing the rotavirus (RV) internal proteins VP2 and VP6 (2/6-VLP) have been shown to induce serum and fecal antibodies as well as protection in mice after intranasal administration with a mutant of E. coli toxin, LT-R192G. To better understand the origin of fecal IgA induced by this protocol, we studied the RV-specific B cell response in systemic and mucosal lymphoid tissues using a flow cytometry assay that allows quantification and phenotypic characterization of RV-specific B lymphocytes. We also assessed the RV-specific antibody-secreting cells in the spleen and intestinal lamina propria (ILP). A remarkably high frequency of RV-specific B cells was found in the respiratory lymphoid tissues and spleen, of which only a minority expressed the alpha4beta7 integrin (intestinal homing receptor). In contrast, but in accordance with alpha4beta7 expression at the induction site, a very low response was observed in intestinal lymphoid tissues (mesenteric lymph nodes and ILP), which did not increase after a second immunization. Thus, intranasal immunization with a nonreplicating antigen does not induce an important number of RV-specific B cells with an intestinal homing profile.