Role of the kallikrein-kinin system of the kidneys in sodium and water transport and its modification by indomethacin

Direct correlation was found in intact rats between the kallikrein activity of the urine, on the one hand, and the diuresis, sodium excretion, and ability of the kidneys to concentrate the urine on the other hand. Small doses of indomethacin (2 mg/kg for 5 days) increased the kallikrein activity of the urine four-fold and, at the same time, increased the diuresis; large doses (5 mg/kg for 5 days) lowered the kallikrein activity of the urine and halved the diuresis, reduced the sodium excretion by two-thirds, and depressed the ability of the kidneys to concentrate the urine. Indomethacin may perhaps modify the synthesis not only of prostaglandins, but also of kallikrein, and this is reflected in the state of the kidney function.All-Union Cardiological Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. I. Chazor.) Translated from Byulleten' Éxperimental'noi Biologii i Meditsiny, Vol. 83, No. 4, pp. 399–400, April, 1977.     

Origin of olfacto-gustatory alliesthesia: Intestinal sensitivity to carbohydrate concentration?

Gustatory and olfactory alliesthesia was observed in nine healthy adult humans who received on three different days an intragastric load of 50 g glucose dissolved into various amounts of water in order to make 100, 200 and 400 ml of solution. Maximal alliesthesia to sweet stimuli was observed with the smallest volume, i.e., highest concentration. Comparison of these results with previous results [7], obtained not by varying the volume but by varying the glucose mass, shows identity. Maximal alliesthesia to olfactory anchovy and Viandox^R was also observed after ingestion of the most concentrated gastric load. Maximal negative alliesthesia was observed about 45 min after the gastric load; thereafter alliesthesia tended to decrease. A gastric 200 ml load containing 40 g Mannitol, a nonabsorbed sugar, was followed by a strong negative alliesthesia to alimentary stimuli. Ten g glucose in 20 ml solution produced a more intense and rapid alliesthesia when injected into the duodenum than when injected into the stomach. It may be concluded that postinjective negative alliesthesia for alimentary stimuli can be caused by intraduodenal concentration of nutrients, probably sensed by duodenal nervous chemoreceptors.     

所谓抗癫(癎)"中成药"中暗地添加抗癫(癎)西药成分的调查

目的:调查所谓抗癫癎“中成药”制剂中是否有西药成分。方法:对北大医院癫癎门诊1995-2005年口服“中成药”制剂就诊的癫癎患者进行苯巴比妥、苯妥英钠、卡马西平、丙戊酸钠四种药物的血药浓度监测,并对结果进行分析。结果:在所监测的患者服用的76种“中成药”中,暗中都添加了上述4种西药成分,其中含有一种西药成分有45种,含有二种西药成分有22种,含有三种西药成分有7种,含有四种西药成分有2种。有44种中药添加了苯巴比妥,占的比例最大,其余依次为苯妥英钠、卡马西平、丙戊酸钠。结论:在所谓抗癫癎的“中成药”中暗地里加西药已成为较普遍的现象,严重地侵犯了患者的权益,妨碍抗癫癎的正规治疗,损害了患者的健康。     

An Assessment of the Genetic Relationship Between Alcohol Metabolism and Alcoholism Risk in Australian Twins of European Ancestry

The present analyses examined genetic influences on alcohol metabolism and their possible relationship to risk of alcohol dependence. Subjects were 206 Australian twin pairs who participated in an alcohol challenge protocol in 1979–1981, in which they were given a 0.75 g/kg dose of alcohol; blood alcohol concentrations (BACs) measured at five times over a 3-hr period after alcohol ingestion were examined. Structural equation modeling, fitting a combined autoregressive and common factor model, indicated significant heritabilities for both men and women (h ² range = 0.19–0.71), with significant parameter heterogeneity as a function of gender. In 1992–1993, both twins from 159 of the alcohol challenge pairs completed a telephone-administered psychiatric diagnostic interview. Repeated-measures MANOVAs were used to examine whether respondent's or cotwin's DSM-III-R alcohol dependence status, or parental history of alcohol problems, was associated with variation in alcohol metabolism. There was some evidence that individuals at increased genetic risk of alcohol dependence [with either a paternal history of alcohol problems (women) or an MZ male cotwin who reported a history of alcohol dependence by 1992–1993] showed lower initial BACs than other groups. However, this effect was not seen in those who themselves had a history of alcohol dependence by interview follow-up, perhaps because this relationship was already masked by a history of excessive drinking at baseline.     

Stress-induced impairment of inhibitory avoidance learning in female neuromedin B receptor-deficient mice

Neuromedin B (NMB) is a mammalian bombesin (BN)-like peptide that exerts its function via the neuromedin B receptor (NMB-R). The NMB/NMB-R system is involved in stress response, and therefore we examined behavioral properties in female mice lacking NMB-R using a restraint-induced stress paradigm. Thirty minutes of restraint in a wire mesh cage constituted a sufficient stress stimulus for mice as evidenced by elevated blood glucose concentrations in stressed wild-type and NMB-R-deficient mice. Using a one-trial passive avoidance test, stressed NMB-R-deficient mice exhibited a marked reduction in memory performance. NMB-R-deficient mice exhibited elevated spontaneous activity in a novel environment compared to non-stressed mutant mice after 30-min stress, and a similar difference was also observed between stressed/non-stressed wild-type mice. An elevated plus maze test showed that the stress stimulus had no effect on anxiety in either wild-type or NMB-R-deficient mice. Furthermore, pain response of wild-type and NMB-R-deficient mice induced by electric foot shock was not affected under either stressed or non-stressed conditions. These results indicate that impaired memory performance in stressed NMB-R-deficient mice is not a consequence of changes in spontaneous activity, anxiety, or pain response, and suggest that the NMB/NMB-R pathway may play a role in regulating the stress response via the neural system that controls learning and memory.     

Procedure for concentration and conditioning of hybridoma cell culture medium for monoclonal antibody purification

Summary Concentration and conditioning the hybridoma cell culture medium is an important step in the monoclonal antibody purification procedure. This report describes a frequent first-step concentration of the hybridoma cell culture medium and the conditioning of the concentrated medium for the affinity purification of the monoclonal antibodies.     

Blood lactate response to overtraining in male endurance athletes

Many physiological markers vary similarly during training and overtraining. This is the case for the blood lactate concentration ([La⁻]_b), since a right shift of the lactate curve is to be expected in both conditions. We examined the possibility of separating the changes in training from those of overtraining by dividing [La⁻]_b by the rating of perceived exertion ([La⁻]_b/RPE) or by converting [La⁻]_b into a percentage of the peak blood lactate concentration ([La⁻]_b,peak). Ten experienced endurance athletes increased their usual amount of training by 100% within 4 weeks. An incremental test and a time trial were performed before (baseline) and after this period of overtraining, and after 2 weeks of recovery (REC). The [La⁻]_b and RPE were measured during the recovery of each stage of the incremental test. We diagnosed overtraining in seven athletes, using both physiological and psychological criteria. We found a decrease in mean [La⁻]_b,peak from baseline to REC [9.64 (SD 1.17), 8.16 (SD 1.31) and 7.69 (SD 1.84) mmol · l⁻¹, for the three tests, respectively; P < 0.05] and a right shift of the lactate curve. Above 90% of maximal aerobic speed (MAS) there was a decrease of mean [La⁻]_b/RPE from baseline to REC [at 100% of MAS of 105.41 (SD 17.48), 84.61 (SD 12.56) and 81.03 (SD 22.64) arbitrary units, in the three tests, respectively; P < 0.05), but no difference in RPE, its variability accounting for less than 25% of the variability of [La⁻]_b/RPE (r=0.49). Consequently, [La⁻]_b/RPE provides little additional information compared to [La⁻]_b alone. Expressing [La⁻]_b as a %[La⁻]_b,peak resulted in a suppression of the right shift of the lactate curve, suggesting it was primarily the consequence of a decreased production of lactate by the muscle. Since the right shift of the curve induced by optimal training is a result of improved lactate utilization, the main difference between the two conditions is the decrease of [La⁻]_b,peak during overtraining. We propose retaining it as a marker of overtraining for long duration events, and repeating its measurement after a sufficient period of rest to make the distinction with overreaching. Accepted: 26 September 2000     

Serum digoxin concentration and half-life in newborns

Summary Serum digoxin concentration and half-life were radioimmunologically determined in 9 mature newborns after 7 days medication with digoxin. The newborns were in respiratory distress treated with continuous positive airway pressure or were suspected to have serious congenital heart disease. Loading dose was 26 µg/kg body weight intravenously and 35 µg/kg body weight orally, respectively. Maintenance dose corresponded to 1/8^th of the digitalization dose twice daily.The serum digoxin level 12 h after the last dose varied between 1.4 and 2.5 ng/ml (mean 2.0 ng/ml, Sx=0.4). The serum half-life of digoxin varied between 21.7 and 42.4 h (mean 30.0 h, Sx=7.7). The mean serum half-life of digoxin of 30 h attained values found in adults without renal disease. This suggests that the serum digoxin levels of newborns which are usually higher if compared with those of adults result from higher digoxin doses per unit body weight and not from diminished digoxin elimination.     

Evidence for interference of vitamin D with PTH/PTHrP receptor expression in opossum kidney cells

 Vitamin D counters the phosphaturic action of parathyroid hormone (PTH) in rats in vivo. The present study was undertaken to examine this interaction using monolayers of Opossum kidney (OK) cells. ³²P uptake, cAMP generation, PTH/PTHrP receptor mRNA expression and intracellular Ca²⁺ [Ca²⁺]_i were measured in (1) control cells, (2) cells exposed to PTH, (3) cells pretreated with 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], and (4) 1,25(OH)₂D₃-pretreated cells exposed to PTH. ³²P uptakes were in (1) 5.00±0.20 (mean ±SE), in (2) 2.30±0.14 (P<0.001 versus group 1), in (3) 4.80±0.24 (P NS versus group 1) and in (4) 3.70±0.20 (P<0.001 versus group 2) nmol P_i/(mg·prot 10 mm). cAMP levels were in (1) 10±3, in (2) 210±8, in (3) 12±4, and in (4) 122±12 pmol cAMP/mg protein (P<0.001 versus group 2). PTH/PTHrP receptor mRNA expression was in relative units: (1) 100±0, (2) 99.5±6.2, (3) 68.7±2.6 (P<0.001 versus group 1), and (4) 34.8±3.3 (P<0.001 versus group 1). In groups 2 and 4 PTH induced equal transient increments in [Ca²⁺]_i. These experiments demonstrate that the effect of vitamin D on phosphate transport is associated with a commensurate diminution in PTH/PTHrP receptor gene expression and PTH-induced cAMP formation but not with Ca²⁺ transients. Vitamin D per se does not affect ³²P uptake or cAMP generation while it slightly decreased PTH/PTHrP receptor gene expression. These observations demonstrate that: (1) 1.25(OH)₂D₃ directly antagonizes the effects of PTH on ³²P uptake in OK cells, (2) this effect is mediated via inhibition of PTH-induced activation of AC/cAMP system, (3) the diminution in PTH-induced cAMP formation may stem at least in part from a decrease in the expression of PTH/PTHrP receptor mRNA. Received: 2 December 1997 / Received after revision: 19 January 1998 / Accepted: 28 January 1998