Topography of median eminence somatostatinergic innervation

Somatostatin (SRIF) in the central nervous system is mostly concentrated in the median eminence (ME). Immunocytochemical methods have revealed high densities of SRIF-positive perikarya between the preoptic area and the periventricular nucleus of the hypothalamus (NPE). The aim of the present study was to define more precisely the specific pathways of SRIF neurons from NPE to the ME. SRIF levels were measured by radioimmunoassay, following various hypothalamic transections. Frontal periventricular sections decreased SRIF-ME content by 70% (P less than 0.01), when located at the anterior end of the ME but no diminution was observed when the cuts were located anteriorly or posteriorly. Parasaggital transections decreased SRIF-ME levels by 50% (P less than 0.05) when located at the outer border of the ventromedial and premammillary nucleus, but the decrease was not significant when cuts were located anteriorly. Taken together, our data indicate that most SRIF-containing neurons, originating in the NPE, do not reach the ME directly along the border of the 3rd ventricle; instead they form a loop across the medial forebrain bundle before re-entering the mediobasal hypothalamus at the ME level.     

A correlative study of the restorative effects of endogenous and exogenous hormones on the Leydig cells, the testis and the epididymis of the regressed hedgehog Effects of hormones on hedgehog Leydig cells

The study of the effects of morphogenesis at puberty on the Leydig cells in the testis of the young hedgehog and of the subsequent changes due to the seasonal varisations, has been done. Furthermore, the restorative changes induced by the exogenous hormones in the Leydig cells and the related sex organs of the regressed hedgehogs have also been studied. It was observed that the Leydig cells from the undifferentiated mesenchyme cell-like nature in the young hedgehog, develop into an adult form possessing large number of lipids, a well-developed Golgi apparatus, complex mitochondria and extensive smooth endoplasmic reticulum. The depletion of the lipids and other regression associated changes are found in the interstitial Leydig cells but not in those situated under tunica albuginea and the latter probably function as lipid storing cells during regression. Pituitary extract, either alone or in combination, but not testosterone, could restore completely the structure of the regressed Leydig cells. Similarly, the restoration of the complete process of spermatogenesis and the structure and function of the epididymis in the regressed hedgehog was found to be dependent upon the synergistic action of both testosterone and the gonadotrophic hormones.     

Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes.

5-Amino-4-imidazolecarboxamide (AICA) riboside, the nucleoside corresponding to AICA ribotide (AICAR or ZMP), an intermediate of the de novo pathway of purine biosynthesis, was found to exert a dose-dependent inhibition on gluconeogenesis in isolated rat hepatocytes. Production of glucose from lactate-pyruvate mixtures was half-maximally inhibited by approximately 100 microM and completely suppressed by 500 microM AICA riboside. AICA riboside also inhibited the production of glucose from all other gluconeogenic precursors investigated, i.e., fructose, dihydroxyacetone, and L-proline. Measurements of intermediates of the glycolytic-gluconeogenic pathway showed that AICA riboside provoked elevations of triose phosphates and fructose-1,6-bisphosphate and decreases in fructose-6-phosphate and glucose-6-phosphate. The effects of AICA riboside persisted when the cells were washed 10 min after its addition but were suppressed by 5-iodotubercidin, an inhibitor of adenosine kinase. AICA riboside provoked a dose-dependent buildup of normally undetectable Z nucleotides. After 20 min of incubation with 500 microM AICA riboside, ZMP, ZTP, and ZDP reached 3, 0.3, and 0.1 mumol/g cells, respectively. Concentrations of ATP were not significantly modified by addition of up to 500 microM AICA riboside when the cells were incubated with lactate-pyruvate but decreased with fructose or dihydroxyacetone. The activity of rat liver fructose-1,6-bisphosphatase was inhibited by ZMP with an apparent Ki of 370 microM. It is concluded that AICA riboside exerts a suppressive effect on gluconeogenesis because it provokes an accumulation of ZMP, which inhibits fructose-1,6-bisphosphatase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of oxygen withdrawal on active and passive electrical properties of arterially perfused rabbit ventricular muscle

Oxygen withdrawal from myocardial cells leads to changes of the transmembrane action potential (mainly action potential shortening), to cellular uncoupling, and to changes of vascular permeability. This study was aimed at the simultaneous measurement of electrical activity and passive electrical properties (extracellular and intracellular longitudinal resistance) in arterially perfused rabbit papillary muscles under different conditions of changed oxygen supply. These included 1) complete anoxia (erythrocyte-free perfusate), 2) hypoxia (PO2 between 23-28 mm Hg, erythrocytes present) in the presence and absence of glucose, and 3) normoxia with erythrocyte-free perfusate. Similarly to myocardial ischemia, rapid cellular uncoupling occurred only after an initial stable period of approximately 17 minutes, and it required complete anoxia. The marked shortening of the action potential developed before cellular uncoupling. In six out of eight experiments, the fibers were inexcitable when uncoupling started. In severe hypoxia, no significant change of internal longitudinal resistance was observed over 35-40 minutes. The time course of the extracellular longitudinal resistance was different from the change in intracellular resistance: A marked decrease occurred almost immediately after the onset of oxygen withdrawal. This decrease was followed by a small increase in conduction velocity, which was most likely due to a change in the interstitial compartment (edema). It was observed during anoxic as well as during hypoxic perfusion. We conclude that 1) cellular uncoupling in arterially perfused tissue requires almost complete oxygen lack and occurs with a delay of more than 10 minutes, 2) marked action potential shortening precedes uncoupling, and therefore can not simply be attributed to an increase in free, intracellular calcium, and 3) vascular endothelial function is more sensitive to oxygen withdrawal than the myocyte.     

New aspects of surgical treatment of cholelithiasis

The interventional endoscopy and new knowledge about the spontaneous course of the cholelithiasis have obtained a far-reaching influence on the indication for operation and the surgical approach. Now as ever the adequate therapy of the symptomatic cholecystolithiasis consists in the early cholecystectomy. Since in the natural course the risk of lethality is small the operation for indication depending on the age and the risk factors given must be made cautiously. This in a still higher degree concerns the asymptomatic cholelithiasis in which at present no general indication for operation is regarded necessary. Due to the low lethality of circa 1% the endoscopic papillotomy has become the therapeutic method of choice in residual and recurrent calculi after cholecystectomy, but also in risk patients with cholecystocholedocholithiasis. The endoscopic papillotomy with stone extraction before the operation suggests a decrease of the operation lethality of 3 to 5% after cholecystectomy with revision of the choledochus.     

Improving primary health care through technological innovation.

As a result of policy changes and developments on the demand side, the importance of technology in primary health care will grow fast. An approach to the implementation of new technologies in primary health care is presented in this article. First we describe the main problems in Dutch primary health care. The second step is to identify new technologies which are becoming available. Subsequently, the interface between these problems and their possible technological resolution has to be found. The fact that a technological innovation appears to be a solution is not sufficient reason for introducing it. There are all kinds of reasons why an innovation that has proved useful in the hospital situation, for example, might be of doubtful use in primary health care. Accordingly, the next step is to assess whether a technological solution to a problem in primary health care is indeed an improvement. To acknowledge the particular situation of primary health care, a scheme has been developed that may be used to determine criteria of evaluation.     

Monocrotaline-induced cardiopulmonary injury in rats. Modification by the neutrophil elastase inhibitor SC39026

Rats were killed after 6 weeks of continuous ingestion of the pneumotoxic alkaloid monocrotaline (2.2 mg/kg/day), the neutrophil elastase inhibitor SC39026 (60 mg/kg/day), or both. Pulmonary reactions were evaluated by light and electron microscopy. Lung endothelial function was monitored by angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Lung hydroxyproline content was measured as an index of interstitial fibrosis. Cardiac right ventricular hypertrophy was determined by the right ventricle to the left ventricle plus septum weight ratio (RV/LV + S). Rats receiving SC39026 alone did not differ significantly from untreated control animals with respect to any of the quantitative endpoints, although rarefaction of Type I pneumocytes was observed in the electron micrographs of these animals. Monocrotaline-treated rats, in contrast, developed a significant increase in RV/LV + S, and exhibited pulmonary edema, inflammation, fibrosis, and muscularization and occlusive mural thickening of the pulmonary small arteries and arterioles. These monocrotaline-induced structural changes were accompanied by decreased lung ACE and PLA activities, and increased PGI2 and TXA2 production, and by an increase in lung hydroxyproline content. Cotreatment with SC39026 ameliorated the monocrotaline-induced pulmonary vascular wall thickening and the cardiac right ventricular hypertrophy. These data suggest that inappropriate neutrophil elastase activity contributes to monocrotaline pulmonary vasculopathy and hypertension. On the other hand, cotreatment with SC39026 had no significant effect on the severity of the monocrotaline-induced lung inflammatory reaction, the pulmonary endothelial dysfunction, or the increase in lung hydroxyproline content.     

Intact parathyroid hormone, ionized calcium and calcium infusion test in the evaluation of hyperparathyroidism in chronic renal failure

We studied the parathyroid function in patients with advanced renal failure by determining their plasma concentrations of ionized calcium (iCa), intact parathyroid hormone (PTH) and its inactive metabolites (PTH-MM). The suppressibility of the parathyroidism was studied with a calcium infusion test. The intact PTH values of the nondialysis and dialysis patients did not statistically differ from each other. The concentrations of PTH-MM were, however, higher in the dialysis patients than in the nondialysis patients (p less than 0.05). The ratio of PTH-MM to intact PTH was lowest in healthy reference subjects and highest in dialysis patients (p less than 0.01), and did not correlate with the degree of intact PTH elevation in the patient groups. The calcium infusion test was carried out on 15 patients. All showed suppression in the elevated plasma intact PTH concentration and in 6 the intact PTH value normalized. The PTH-MM value did not normalize in any of the patients. During oral calcium treatment the degree of intact PTH suppression at an achieved concentration of plasma iCa was predictable from the infusion test. Three patients were parathyroidectomized after the calcium infusion test. In 2 of these elevated intact PTH normalized within 24 h while in 1 no change took place. In this latter case on clinical improvement was noted. We conclude that the determination of plasma intact PTH concentration especially of combined with plasma iCa value is a reliable means of studying the hyperparathyroidism associated with chronic renal failure.