Vasopressin release and firing of supraoptic neurosecretory neurones during drinking in the dehydrated monkey

A close relationship exists between drinking and the release of vasopressin, the two main factors responsible for the maintenance of body water content. Whereas the participation of peripheral factors, such as oropharyngeal stimulation, seems obvious in the metering of fluid intake and in thirst satiation, very little is known about their influence on vasopressin release. In the present experiments, the influence of drinking on vasopressin release was studied using both biochemical and electrophysiological approaches.In one group of monkeys made thirsty by water deprivation, the subsequent drinking of water during a 5–8 min induced: i) a short-term response, consisting of an abrupt fall in plasma vasopressin concentration which was independent of osmolality, occurred at the time of drinking and was partly reversed after the cessation of drinking, and ii) a longer lasting response, consisting of a slow diminution of plasma vasopressin concentration as the intestinal absorption of water progressed. In another group of thirsty monkeys, extracellular recordings were made during drinking from cells which were identified as neurosecretory neurones of the supraoptic nucleus, a number of them being considered vasopressin secreting on the basis of their phasic pattern of firing. Their firing decreased considerably during the periods of water intake and recovered to control levels immediately after-wards.The decrease in vasopressin release at the onset of water intake, the diminution in the firing rate of the neurones, the short latency and the reversibility of these events after cessation of drinking, suggest that a reflex inhibition of vasopressin-secreting neurones occurs which is probably induced by peripheral stimuli and most likely via oropharyngeal or other visceral receptors. It is postulated that this reflex inhibition of vasopressin release may participate in some active manner in the anticipatory mechanisms of thirst satiation.     

Resistance exercise training and the orthostatic response

Resistance exercise has been suggested to increase blood volume, increase the sensitivity of the carotid baroreceptor cardiac reflex response (BARO), and decrease leg compliance, all factors that are expected to improve orthostatic tolerance. To further test these hypotheses, cardiovascular responses to standing and to pre-syncopal limited lower body negative pressure (LBNP) were measured in two groups of sedentary men before and after a 12-week period of either exercise (n = 10) or no exercise (control, n = 9). Resistance exercise training consisted of nine isotonic exercises, four sets of each, 3 days per week, stressing all major muscle groups. After exercise training, leg muscle volumes increased (P?P = 0.00) by 2.0 (0.5)?kg, leg compliance and BARO were not significantly altered, and the maximal LBNP tolerated without pre-syncope was not significantly different. Supine resting heart rate was reduced (P = 0.03) without attenuating the heart rate or blood pressure responses during the stand test or LBNP. Also, blood volume (¹²⁵I and ⁵¹Cr) and red cell mass were increased (P?相似文献   

Sleep related breathing disorders in older men: A search for underlying mechanisms

—The incidence of sleep-related breathing disorders (SRBDs) associated with hemoglobin desaturation was determined by nocturnal polygraphic evaluations in 26 healthy men, aged 55–70 years. Sixteen subjects (62%) had abnormal rates of at least 12 episodes per hour of sleep: 8 had occlusive, and 8 had central apnea or hypopnea. During waking ten of 16 SRBD subjects and only one subject without SRBDs exhibited either an elevated nasopharyngeal airway resistance (n=4) or a reduced ventilatory response to hypercapnia (n=4) and/or hypoxia (n=3). However, these abnormalities were not related to the type or severity of SRBDs, and 6 subjects with SRBDs demonstrated no respiratory defect. We conclude that SRBDs have a very high incidence in older males and are not usually secondary to pulmonary cardiac, neurological, or behavioral disorders. Additionally, we hypothesize that abnormalities in ventilatory control or upper airway resistance contribute to SRBDs, but depression of brain stem reticular formation activity during sleep plays a primary role in these disorders. Factors related to both aging and SRBDs are reviewed. These include reduced chemoreceptor responses, altered steroid hormone metabolism, and use and metabolism of hypnotic drugs and alcohol.     

Multiple genetic typing of Salmonella enterica serotype typhimurium isolates of different phage types (DT104, U302, DT204b,and DT49) from animals and humans in England,Wales, and Northern Ireland

Salmonella enterica serotype Typhimurium is a common cause of salmonellosis among humans and animals in England, Wales, and Northern Ireland. Phage types DT104 and U302 were the most prevalent types in both livestock and humans in 2001. In addition, Salmonella serotype Typhimurium DT204b was responsible for a recent international outbreak involving England. A total of 119 isolates from humans (n = 28) and animals or their environment (n = 91), belonging to DT104 (n = 66), U302 (n = 33), DT204b (n = 12), and DT49 (n = 8), were fingerprinted by a combination of well-established genetic methods (pulsed-field gel electrophoresis [PFGE], PstI/SphI [PS] ribotyping, and plasmid profiling). The different techniques identified different degrees of polymorphism (from greatest to least, plasmid profiling [40 types], PS ribotyping [34 types], and PFGE [23 types]). It seems clear that a prevalent genomic clone, as well as a variety of less frequent clones, is present for each of the phage types. In most cases, the prevalent clones appeared within isolates from several animal species and from several geographical locations. We did not find clear evidence of a higher degree of diversity for any of the animal species included, or of any link between isolates from particular animal species and humans. The data presented show the inaccuracy of drawing epidemiological conclusions based on a single fingerprinting method. Strains that share one of the markers do not necessarily belong to the same clone, and a multiple typing approach is required to enable enough discrimination to track strains for epidemiological investigations.     

Intrarenal dopamine coordinates the effect of antinatriuretic and natriuretic factors

The precision by which sodium balance is regulated suggests an intricate interaction between modulatory factors released from intra- and extrarenal sources. Intrarenally produced dopamine has a central role in this interactive network. Dopamine, produced in renal tubular cells acts as an autocrine and paracrine factor to inhibit the activity of Na+,K+-ATPase as well as of a number of sodium influx pathways. The natriuretic effect of dopamine is most prominent under high salt diet. The antinatriuretic effects of noradrenaline, acting on alpha-adrenoceptors and angiotensin II are opposed by dopamine as well as by atrial natriuretic peptide (ANP). Several lines of evidence have suggested that ANP acts via the renal dopamine system and recent studies from our laboratory have shown that this effect is attributed to recruitment of silent D1 receptors from the interior of the cell towards the plasma membrane. Taken together, the observations suggest that dopamine coordinates the effects of antinatriuretic and natriuretic factors and indicate that an intact renal dopamine system is of major importance for the maintenance of sodium homeostasis and normal blood pressure.     

Prevalence of hepatitis-C virus RNA in serum and throat washings of children with chronic hepatitis

Serum samples from 46 children with chronic and probably transfusion acquired hepatitis were tested for the presence of hepatitis C virus (HCV) RNA by a “nested” polymerase chain reaction (PCR) assay, to judge a possible risk of HCV transmission from these patients. In 73% of the samples, viral RNA was detected, indicating a high virus prevalence in this patient group. High titers of HCV-RNA were observed in some sera as shown by the detection of virus in some samples even at dilutions of 10^?3. Comparison of simultaneously obtained PCR results and ALT values revealed no significant correlation between virus presence in serum and higher ALT levels. It was, however, shown that unusually high ALT values may reflect a high titer of viral RNA in serum. To investigate the prevalence of viral RNA in saliva, which could be a vehicle of virus transmission, 35 throat washing samples from the HCV-infected children were screened by PCR. Using three different sample preparation procedures, 20% of the throat washings were found to be positive for HCV-RNA. This indicates a prevalence of virus in this fluid lower than that reported previously. © 1994 Wiley-Liss, Inc.     

Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia.

Linkage analyses suggest that chromosome 22q12-13 may harbor a shared susceptibility locus for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of a sample from the Faeroe Islands we have previously reported association between both disorders and microsatellite markers in a 3.6 cM segment on 22q13. The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13. Nine SNPs located in these genes and one microsatellite marker (D22S279) were applied in an association analysis of two samples: an extension of the previously analyzed Faeroese sample comprising 28 distantly related cases (17 BPD, 11 SZ subjects) and 44 controls, and a Scottish sample including 162 patients with BPD, 103 with SZ, and 200 controls. In both samples significant associations were observed in both disorders with predominantly GPR24 SNPs and haplotypes. In the Faeroese sample overall P-values of 0.0009, 0.0054, and 0.0023 were found for haplotypes in BPD, SZ, and combined cases, respectively, and in the Scottish sample overall P-values of 0.0003, 0.0005, and 0.016 were observed for similar groupings. Specific haplotypes showed associations with lowest P-values of 7 x 10(-5) and 0.0006 in the combined group of cases from the Faeroe Islands and Scotland, respectively. The G protein-coupled receptor 24 encoded by GPR24 binds melanin-concentrating hormone (MCH) and has been implicated with feeding behavior, energy metabolism, and regulation of stress and mood. To our knowledge this is the first study reporting association between GPR24 and BPD and SZ, suggesting that GPR24 variants may confer susceptibility to both disorders.     

Performance characteristics of four immunoassays for antiepileptic drugs on the IMMULITE 2000 automated analyzer

Carbamazepine, phenobarbital, phenytoin, and valproic acid are commonly used antiepileptic drugs that show complicated pharmacokinetic behavior Nonisotopic immunoassays are used routinely to monitor these drugs, and assay specificity is important to obtain accurate results. By using samples from subjects receiving each of these antiepileptic medications, competitive immunoassays for them were evaluated on an IMMULITE 2000 automated chemiluminescent analyzer (Diagnostic Products, Los Angeles, CA). Phenytoin assays were evaluated using an additional set of samples from patients with abnormal renal function. All 4 methods were linear, had imprecision of less than 10%, and compared well with other commercial immunoassays. A positive bias was observed for phenytoin measured in samples from uremic patients compared with a high-performance liquid chromatography reference method. The molar cross-reactivity of carbamazepine-10,11-epoxide was 12% in the carbamazepine assay. Phenytoin metabolites and fosphenytoin had substantial cross-reactivity in the phenytoin assay. All antiepileptic drug assays performed well and are suitable for use in monitoring patients receiving antiepileptic drug therapy. One possible exception is the phenytoin assay with samples from patients with renal insufficiency.     

Heart tumors in children and adults: clinicopathological study of 59 patients from a surgical center.

BACKGROUND: Heart tumors are rare lesions with variegated histological types. Their clinicopathological features could be more comprehensively categorized. METHODS: This is a 19-year retrospective study of 17 infants/toddlers (<2 years of age) and 42 patients aged between 14 and 79 years (mean = 51.5) in a surgical center. RESULTS: Congenital tumors (n = 17; 29%), including rhabdomyomas (n = 9), ventricular fibromas (n = 6), and hemangiomas (n = 1), required surgery mainly because of mass effect. Familial myofibromatosis was the only embolic congenital lesion. Acquired benign tumors (n = 28; 47%) included myxomas (n = 21), fibroelastomas (n = 3), myofibroblastic inflammatory tumors (n = 2), and lipomas (n = 2). Eight (29%) were revealed by systemic embolization. These benign noncongenital tumors were all treated by complete resection, except for an incompletely resected lipoma of the mitral valve. Postoperative arrhythmia (n = 1) and pericardial effusion (n = 3) were the only complications. Primary sarcomas (n = 8; 14%) were mostly vascular tumors (five of eight), and patients with high-grade tumors had a mean survival of 15 months (n = 5). Cardiac metastases (n = 6; 10%) were from carcinomas (n = 3) or sarcomas (n = 3); apart from a necrotic metastasis, all patients died (mean survival of 6 months). CONCLUSIONS: This study shows that, regardless of patients' age, heart tumors can be classified as: (a) congenital lesions, which are spontaneously nonprogressive or regressive lesions possibly requiring surgery mainly because of mass effect; (b) acquired benign tumors, which are lesions requiring surgery often because of embolization risk; and (c) primary and secondary malignant tumors, which are lesions with globally poor prognosis but with some indications for resection.