Interrelations between age and plasma renin,aldosterone and cortisol,urinary catecholamines,and the body sodium/volume state in normal man

Summary Interrelations between age and plasma renin, aldosterone and cortisol levels, urinary catecholamines, plasma and blood volumes, exchangeable body sodium and blood pressure were studied in 28 young (19 to 29 years), 16 middle-aged (32 to 58 years) and 15 elderly (60 to 74 years) healthy subjects. Supine and upright plasma renin and supine aldosterone levels decreased while urinary noradrenaline excretion rate increased progressively with aging (r0.34;p<0.05), with significant differences in mean values between young and elderly subjects (p<0.02). There was also an age-related decrease in upright plasma aldosterone concentration, although this was not statistically significant. Furthermore, mean plasma cortisol concentrations increased in response to upright posture in elderly (+50%;p<0.02), but not in young (–10%) or middle-aged (–8%) subjects. Blood pressure correlated with age (r=0.35;p<0.05) or noradrenaline excretion rate (r=0.34) in the entire study population and with blood volume in the elderly (r=0.68), but not in the young or middle-aged study groups. There were no significant age-related differences in the body sodium/volume state, basal plasma cortisol levels or urinary adrenaline excretion rate, and plasma renin or aldosterone levels did not correlate with these parameters or with blood pressure. It is concluded that the influence of age on plasma renin or aldosterone levels, plasma cortisol responsiveness to upright posture, and urinary noradrenaline excretion should be taken into consideration, whenever these factors have to be interpreted in patients with arterial hypertension or other clinical disorders. Furthermore, these data are consistent with the possibility that in normal man increases in supine blood pressure with aging may be related at least partly to concomitant changes in free peripheral noradrenaline.This investigation was supported by the Swiss National Science Foundation     

Melatonin secretion in the Mashona mole-rat, Cryptomys darlingi--influence of light on rhythmicity

The hormone melatonin is synthesised and secreted from the pineal gland in darkness and triggers the daily and seasonal timing of various physiological and behavioural processes. The Mashona mole-rat, Cryptomys darlingi, lives in subterranean burrows that are completely sealed and is therefore rarely, if ever, exposed to light under natural conditions. Hence, this species is of particular interest for studies on rhythms of melatonin secretion. We investigated how plasma melatonin concentrations of the Mashona mole-rat responded to exposure to a long-term standard photoperiod of 12 h light, 12 h dark (12:12 LD), constant light (LL) and constant dark (DD). In addition, we examined whether plasma melatonin concentration was coupled to locomotor activity. Mashona mole-rats displayed rhythms of plasma melatonin concentration that appeared entrained to the standard LD photoperiod, suggesting that the mole-rat is capable of perceiving and entraining to this photic zeitgeber. Furthermore, under chronic constant lighting conditions (DD, LL), circadian rhythms in plasma melatonin concentration were observed, suggesting the possible existence of an endogenous rhythm. Light suppressed melatonin secretion, but constant light did not abolish the rhythm of plasma melatonin concentration. Between active and non-active animals, no difference in plasma melatonin concentration was found for any of the sequential photoperiods (LD1 DD, LD2, LL), tentatively suggesting that the rhythm of melatonin secretion is uncoupled from that of locomotor activity.     

采用MDA-MB-231细胞膜进行表皮生长因子受体活性的检测

目的　探讨能否直接利用肿瘤细胞膜进行表皮生长因子受体 (Epidermalgrowthfactorreceptor,EGFR)催化活性检测。方法　首先筛选出EGFR基因表达水平相对较高的细胞株MDA MB 2 31,通过差速离心制备细胞膜 ,采用Westernblotting检测EGFR催化磷酸化的程度。结果　底物被磷酸化 ,加入特异性拮抗剂AG14 78后 ,磷酸化被抑制。结论　利用肿瘤细胞膜检测EGFR活性的设想是成立的 ,并且其方法简便、经济。     

Quantitative displacement of blood acid base equilibrium in acutely water depleted dogs

Summary Dogs were water depleted 2% of their body weight by the intraperitoneal injection of a hyperosmotic solution of saline and glucose (550 mOsm/l). During a 3-h experiment these water-depleted (WD) animals showed a significant decrease in blood pH, base excess (BE) and plasma bicarbonate (Bic_p) and an increase in both hematocrit (Ht) and blood buffer capacity (BBC). These changes were quantitatively time-dependent. The rate change of pH, BE, and Bic_p were –0.072 units h^–1, –4.7 mEq/l h^–1, and 2.9 mEq/l h^–1, respectively. As control dogs showed no significant time-dependent changes in their blood acid-base status, the observed modifications in the experimental dogs were ascribed to water depletion. Increased endogenous acid production related to tissue hypoxia is suggested to be the mechanism that could explain the increased fixed acid accumulation observed in the water-depleted animals.     

Acute hypervolemia does not improve arterial oxygenation in maximally exercising thoroughbred horses

Recently, it was reported that acute hypervolemia improves arterial oxygen tension in human athletes known to experience exercise-induced arterial hypoxemia. Since exercise-induced arterial hypoxemia is routinely observed in racehorses and is known to limit performance, we examined whether pre-exercise induction of acute hypervolemia would similarly benefit arterial oxygenation in maximally exercising thoroughbred horses. Two sets of experiments, namely, placebo [intravenous (IV) physiological saline] and acute hypervolemia (IV 7.2% NaCl, causing an 18.2% expansion of plasma volume) studies were carried out in random order on 13 healthy, exercise-trained thoroughbred horses, 7 days apart. An incremental exercise protocol leading to 120 s of galloping at 14 m s^–1 on a 3.5% uphill incline was used. Galloping at this workload elicited maximal heart rate and induced pulmonary hemorrhage in all horses in both treatments. In the placebo study, arterial oxygen tension decreased to 76.1 (2) mmHg (P<0.0001) at 30 s of maximal exertion, but further significant changes did not occur as exercise duration increased to 120 s [arterial oxygen tension 72.4 (2) mmHg]. A significant arterial hypoxemia also developed in galloping horses in the acute hypervolemia study [arterial oxygen tension at 30 and 120 s was 76.7 (1.7) and 71.9 (1.6) mmHg, respectively], but significant differences between treatments could not be demonstrated. In both treatments, a similar desaturation of arterial hemoglobin was also observed at 30 s of maximal exercise, which intensified with increasing exercise duration as hyperthermia, acidosis and hypercapnia intensified. Thus, acute expansion of plasma volume did not benefit arterial oxygenation in maximally exercising thoroughbred horses.     

Body weight set point studies in weanling rats with dorsomedial hypothalamic lesions (DMNL rats)

In order to further characterize a previously postulated "organismic" set point, weanling DMNL and control (CON) rats were maintained on lab chow ad lib (AL) for 55 post-operative days. Subsequently, some DMNL and CON rats were food-restricted (REST) to 80% of the food intake of their AL-fed counterparts for 24 days. At this point, representative rats from each group were killed by decapitation and the remaining animals were re-fed AL and killed 7 and 22 days thereafter. At the end of REST, both DMNL and CON showed significant weight loss, which was greater in CON than in DMNL rats. After 7 days of refeeding, DMNL rats normalized their body weights but re-fed CON still weighed less than AL-fed CON 22 days after refeeding. Food intake in formerly REST groups overshot on refeeding for 7 days, but this was significant only in DMNL rats. Notably, during this time formerly REST-DMNL ate as much as AL-fed CON. Efficiency of food utilization was normal in DMNL during AL feeding and became reduced on REST as it did in REST-CON. Notably, on refeeding formerly REST-DMNL rats overshot that of AL-fed DMNL rats by the same magnitude as previously REST-CON overshot the values of AL-fed CON. After 22 days of refeeding, this overshoot was still evident in DMNL but not in CON. At the end of the REST period, plasma insulin and glucose were similar in AL-fed DMNL and AL-fed CON. They were significantly and comparably reduced in both REST-DMNL and REST-CON compared to the AL-fed DMNL and AL-fed CON. On refeeding these changes normalized within seven days. At the end of REST, plasma free fatty acid concentrations were higher in REST-DMNL and REST-CON than in AL-fed DMNL and AL-fed CON. After seven days of refeeding they normalized only in formerly REST-CON. Plasma glycerol and total protein were normal throughout all groups, as was carcass protein. Carcass fat was equivalently reduced in both DMNL and CON at the end of REST and normalized 7 days after refeeding. AL-DMNL had the same carcass fat as AL-CON and REST-DMNL had the same carcass fat as REST-CON. In conjunction with previously reported normal anabolic hormone levels the data suggest that DMNL rats are not growth-retarded but are merely scaled down in size without compromise of their homeostatic competence. We take this as strong evidence for the existence of an "organismic" set point.     

Duration of benzodiazepine clinical activity: Lack of direct relationship with plasma half-life

The anxiolytic activity and tolerance of two dosage schedules of prazepam, a long plasma half-life benzodiazepine, were compared under double-blind conditions in two groups of 10 inpatients each who met Research Diagnostic Criteria for Generalized Anxiety Disorder and presented chronic and severe symptomatology. Patients received prazepam 40 mg per day on one of two dosage schedules: 1) divided dosage (DD) - 10 mg in the morning and at noon and 20 mg in the evening; or 2) single dosage (SD) - 40 mg in the evening. The 3 weeks of therapy were preceded and followed by 1 week of wash-out for baseline and follow-up assessments, which were performed weekly with the Hamilton Anxiety Scale, Clinical Global Impression, rating of morning drowsiness and evening worsening of symptoms, and patient self-rating of anxiety by means of a visual analogue scale performed both in the morning and in the afternoon. The results showed a clear superiority of the DD over the SD schedule: better anxiolytic efficacy on the Hamilton Anxiety Scale (P<0.0005) and on both morning and afternoon visual analogue scales (P<0.01 andP<0.0002); less morning drowsiness (P<0.0001); and steadier anxiolytic effect during the daytime, as globally rated by the investigator (P<0.0001) or measured by morning-afternoon differences on the visual analogue scale (P<0.005). These results suggest that plasma pharmacokinetics alone may not be sufficient to predict the duration of benzodiazepine anxiolytic activity.     

The effects of CaEDTA injection on lead,zinc, copper and ALAD in erythrocyte,plasma and urine in lead-exposed workers: a 24-h observation

Summary To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the concentrations of lead, zinc and copper in plasma, erythrocyte and urine, and the delta-aminolevulinic acid dehydratase (ALAD) activity in erytrocyte, we administered CaEDTA in 1-h intravenous infusion to ten male gun metal founders with blood-lead concentration of 39 to 64 g/dl (mean 49 g/dl). We found that the plasma concentration of lead, following a rapid rise within the first 3 h, fell temporarily to the level significantly lower than the initial level 19 h after start of the infusion. The plasma concentration of zinc fell to the minimal level 5 h after the infusion; and the erythrocyte concentration of zinc and the ALAD activity concurrently rose to the maximal level 5 h after the infusion. By contrast, no significant alteration was observed in the concentrations of copper in plasma and erythrocyte. The maximal level of urinary metal excretion was attained during the period between 1 and 2 h after start of CaEDTA infusion for lead; within 2 h for zinc; and between 2 and 4 h for copper. The urinary metal excretion returned to the initial level 14 to 24 h after infusion for zinc and copper; but lead excretion was still higher than the initial level during this period. The difference in the kinetics of the three metals following CaEDTA injection is discussed in the light of these findings.     

Plasma fibronectin in psoriatic arthritis subgroups

Summary Plasma from 38 patients suffering from one of the five broad clinical subgroups of Psoriatic Arthritis (PA) were studied for soluble plasma Fibronectin (pFn). The mean total concentration of pFn was 453.03g/ml ± 142.83 SD, with a significant statistical difference (p<0.01) versus a healthy control group matched with respect to sex and age. In order to evaluate the biological role that pFn might play in this pathological condition, observed concentrations were correlated with the degree and duration of the psoriasis and arthritis. In addition, pFn was correlated to some biohumoral parameters that are modified during inflammatory processes (ESR, CRP, sCu, sFe, Hb) and to uric acid levels. Tissue typing (HLA) was done where possible. From our observations, we suggest that pFn most likely is not an acute phase protein and rather than having specificity for a particular disease, might, in widespread and severe cases be,a general and useful marker of the connective-tissue organizing and repairing response, following its injury.