Search

Background Despite the increasing use of Roux-en-Y gastric bypass (RYGBP) in the treatment of morbid obesity, data about postoperative nutritional deficiencies and their treatment remain scarce. Objective The aim of this study was to evaluate the efficacy of a standard multivitamin preparation in the prevention and treatment of nutritional deficiencies in obese patients after RYGBP. Design This was a retrospective study of 2 y of follow-up of obese patients after RYGBP surgery. Between the first and the sixth postoperative months, a standardized multivitamin preparation was prescribed for all patients. Specific requirements for additional substitutive treatments were systematically assessed by a biologic workup at 3, 6, 9, 12, 18, and 24 mo. Results A total of 137 morbidly obese patients (110 women and 27 men) were included. The mean (+/-SD) age at the time of surgery was 39.9 +/- 10.0 y, and the body mass index (in kg/m(2)) was 46.7 +/- 6.5. Three months after RYGBP, 34% of these patients required at least one specific supplement in addition to the multivitamin preparation. At 6 and 24 mo, this proportion increased to 59% and 98%, respectively. Two years after RYGBP, a mean amount of 2.9 +/- 1.4 specific supplements had been prescribed for each patient, including vitamin B-12, iron, calcium + vitamin D, and folic acid. At that time, the mean monthly cost of the substitutive treatment was $34.83. Conclusion Nutritional deficiencies are very common after RYGBP and occur despite supplementation with the standard multivitamin preparation. Therefore, careful postoperative follow-up is indicated to detect and treat those deficiencies.

The plasma levels of either brain natriuretic peptide (BNP) or the N-terminal fragment of the prohormone (NT-proBNP) have recently gained extreme importance as markers of myocardial dysfunction. Patients with type 2 diabetes are at high risk of developing cardiovascular complications. This study was aimed to assess whether plasma NT-proBNP levels are at similar levels in type 2 diabetics with or without overt cardiovascular diseases.We assayed plasma NT-proBNP in 54 type 2 diabetics, 27 of whom had no overt macro- and/or microvascular complications, while the remaining ones had either or both. The same assay was carried out in 38 healthy control subjects age and sex matched as a group with the diabetics.Plasma NT-proBNP was higher in diabetics (median 121 pg/ml, interquartile range 50-240 pg/ml, ) than in those without complications (37 pg/ml, 21-54 pg/ml, P0.01). Compared with the controls (55 pg/ml, 40-79 pg/ml), only diabetics with vascular complications had significantly increased plasma NT-proBNP levels (P0.001). In the diabetics, coronary heart disease and nephropathy (defined according to urinary excretion of albumin) were each independently associated with elevated values of plasma NT-proBNP.In type 2 diabetes mellitus, patients with macro- and/or micro-vascular complications exhibit an elevation of plasma NT-proBNP levels compared to corresponding patients with no evidence of vascular disease. The excessive secretion of this peptide is independently associated with coronary artery disease and overt nephropathy. The measurement of circulating NT-proBNP concentration may therefore be useful to screen for the presence of macro- and/or microvascular disease.

It is well established that sexual dimorphism exits within the immune system. Females have higher levels of immunoglobulins, greater antibody response to antigens, and higher incidence of autoimmune diseases, such as systemic lupus erythematosus, Grave’s disease, and Hashimoto thyroiditis than males. Spontaneous autoimmune syndromes in mice are more prevalent and of greater severity in females compared with males, and the course of the disease can be modulated by changes in levels of gonadal steroids. A sexual dimorphism is also present in the pituitary-adrenal function: females have higher corticosterone levels and higher corticosteroidogenesis. In the context of the immune-neuroendocrine interactions, we investigated the effects of gonadectomy and sex hormone therapy on endotoxin-stimulated hypothalamo-pituitary-adrenal axis. Whereas endotoxin-induced corticosterone release is invariable throughout the different stages of the oestrus cycle, gonadectomy in both male and female mice leads to enhanced adrenal and immune responses to endotoxin. Interestingly, these enhanced adrenal and immune responses can be completely reversed by testosterone treatment regardless of the sex of the mice. Studies performed over development confirm the role of endogenous testosterone in modulating the endotoxin-induced corticosterone secretion. Indeed, corticosterone response to endotoxin is maximal before puberty when endogenous testosterone levels are low and declines in postpubertal and adult mice. In conclusion, all these data support a sex steroid hormone basis for a neuroendocrine-immunologic sexual dimorphism.

Bidirectional interactions between the immune system and the hypothalamo-pituitary-adrenal (HPA) axis may represent an important mechanism that prevents overexuberant immune responses. In this network, cytokines play an important role in modulating the HPA axis response at all three levels: the hypothalamus, the pituitary gland, and the adrenals. Acute effects of cytokines are produced at the hypothalamic level by altered release of hypophysiotropic hormones, whereas pituitary and adrenal actions are slower but probably more important in response to prolonged release of cytokines, as it occurs in infection or inflammation. Further studies are needed to determine the precise mechanism through which circulating cytokines affect the HPA axis function within the central nervous system and to evaluate the relevance of these interactions in physiologic and pathophysiologic situations in humans.

Several lines of evidence indicate a role for neuropeptide Y (NPY) in the modulation of the corticotroph axis. In two separate studies reported here, the concentrations of NPY and noradrenaline (NA), as well as corticotropin-releasing factor (CRF) and arginine vasopressin (AVP), were measured in extracts of individual rat hypothalamic nuclei after various manipulations producing either a state of chronic glucocorticoid excess or depletion, and also following repeated restraint stress. Alterations induced in the activity of hypothalamic neurones were inferred from the respective changes in these concentrations. 12 days after bilateral adrenalectomy (ADX), NPY levels were decreased by 24% in the arcuate nucleus (ARC) and 23% in the paraventricular nucleus (PVN, p < 0.05 vs controls). Forced immobilization of the animals for 4 h each day for 9 consecutive days (repeated stress) also decreased NPY content of the ARC by 25% (p < 0.01 vs controls), an effect blocked by the administration of glucocorticoids. NA levels in both hypothalamic nuclei were unaffected by repeated stress or ADX. Administration of glucocorticoids in the first of these studies induced decreases in NA levels by 15% and 25% in the ARC and PVN respectively (p < 0.05 vs controls). However, in subsequent experiments no significant effect of glucocorticoids on NA was observed. Our results demonstrate that the activity of the hypothalamic NPY-ergic neurones is modulated by glucocorticoids and by chronic stress. They also suggest that brainstem catecholaminergic and hypothalamic NPY-ergic neurones are differentially affected by altered glucocorticoid concentrations or by chronic stress, possibly in a stimulus-specific way.

Emergencies in pituitary disease are not common. They can result from the failure of the pituitary gland to secrete one or more pituitary hormones, or from neuro-ophthalmological symptoms due to the mass effect of an expanding hypothalamic-pituitary tumour. Loss of hormone secretion, particularly ACTH and, to a lesser extent, TSH, can rapidly become life-threatening and requires urgent replacement therapy. Acute severe hypopituitarism should be vigorously treated as an emergency with a glucocorticoid preparation. Neuro-ophthalmological symptoms such as visual impairment, sudden onset of severe headache and alteration of the level of consciousness should prompt appropriate radiological investigations, since this may well call for emergency surgery.

Human hypothalamic growth hormone-releasing factor (GRF) was purified by gel filtration and reverse-phase HPLC. Bioassay and two radioimmunoassays of different specificity revealed the presence of two major forms of GRF-activity which coelute with human pancreas GRFs, hpGRF-44-NH2 and hpGRF-40 previously characterized in pancreas tumors. The bioactive material coeluting with hpGRF-44-NH2 is recognized by two antibodies which are directed against the amidated COOH-terminal sequence and the central portion of the GRF-44 peptide. The bioactive GRF which coelutes with hpGRF-40 reacts only with the antibody directed against the central portion of hpGRF. These data strongly suggest that the human hypothalamus contains the same major forms of GRF that were identified in pancreas tumors responsible for acromegaly in the absence of a pituitary tumor.

Summary The hypothalamo-pituitary-adrenal axis is controlled by complex regulatory mechanisms. Numerous factors such as CRF, vasopressin, oxytocin, angiotensin II and conceivably other hormones—all controlled by various substances acting on central locations—stimulate the release of the stress hormone ACTH. On the other hand, glucocorticoids inhibit the secretion of ACTH by acting at the hypothalamic and/or pituitary level. The release of ACTH is therefore the final outcome of the interactions between the hypothalamus, the adrenal gland and possibly other organs. The multimolecular nature of the factors responsible for the control of the pituitary-adrenal axis is an attractive hypothesis because of the great variety of stress stimuli. The various factors could have specific roles in various stress situations. They provide a highly sensitive mechanism regulating very finely the stress hormone in response to a whole variety of endogenous and exogenous stimuli. Depending on the type of stress, they may therefore singly or in combination affect the amount and duration of ACTH and steroid secretion. The released glucocorticoids may then produce their numerous effects on inflammatory and immunological processes, carbohydrate metabolism, shock and water balance. It has been postulated that these effects may be important in order to prevent host responses from over-reacting to stress and threatening homeostasis. However, proof of the necessity of the glucocorticoid hypersecretion in response to stress remains elusive.

This study in conscious normotensive rats was performed to assess the effect of the vasoconstrictor peptide, neuropeptide Y (NPY), on blood pressure responsiveness to exogenous norepinephrine in endotoxaemia. NPY and endotoxin were infused at doses which had no effect on blood pressure, whether given alone or in combination. Endotoxin markedly reduced the pressor responses to bolus injections of norepinephrine. However, blood pressure responsiveness could be enhanced by infusing NPY simultaneously with the endotoxin. It is suggested that low dose NPY infusions may be clinically useful in reversing the reduced vascular responsiveness to pressor amines in shock.

Following the success of ergot alkaloids and their synthetic derivatives in treating a variety of pathophysiological disturbances, efforts have been concentrated on the synthesis of new derivatives and partial structures with the aim of dissecting out a specifically dopaminomimetic pharmacophore. Accordingly CV 205–502, a structure which superposes the linear benzo [g] quinoline segment of apomorphine on the substituted pyrrolo [3,4-g] quinoline moiety of the ergolines was designed. This study was performed in normal young volunteers to investigate the effect of single oral doses of CV 205–502 on plasma prolactin levels and on other endocrine parameters (GH, LH, FSH, TSH and cortisol) as well as on tolerability. 10 volunteers participated in a dose-ranging study. They received single oral doses of 0.01 to 0.09 mg CV 205–502, in order to assess the prolactin suppressant action. 6 volunteers were given a dose of 0.06 mg CV 205–502 in order to determine the endocrine profile of the compound. The duration of action of 0.06 mg CV 205–502 was investigated in 6 subjects by measuring plasma PRL and GH levels for 48 h. The results show strong dose-dependent suppression of PRL appearing following doses between 0.04 and 0.09 mg of CV 205–502. PRL was markedly suppressed for more than 24h. and the peaks of the normal sleep profile were abolished. Intermittent transient GH increases occurred during the first 6 hours; sleep profiles were normal. Compared with placebo values, no changes were seen in the levels of any other hormone except TSH, which decreased. Tolerability was good and no drug attributable changes in safety measures occurred. This study demonstrates that CV 205–502 is a potent and long acting PRL suppressant compound and suggest that this novel octahydrobenzo [g] quinoline will prove to be a therapeutically useful dopaminomimetic compound.

Neuropeptide Y (NPY) is present in the adrenal medulla, in sympathetic neurons as well as in the circulation. This peptide not only exerts a direct vasoconstrictor effect, but also potentiates the vasoconstriction evoked by norepinephrine and sympathetic nerve stimulation. The vasoconstrictor effect of norepinephrine is also enhanced by salt loading and reduced by salt depletion. The purpose of this study was therefore to assess whether there exists a relationship between dietary sodium intake and the levels of circulating NPY. Uninephrectomized normotensive rats were maintained for 3 weeks either on a low, a regular or a high sodium intake. On the day of the experiment, plasma levels of NPY and catecholamines were measured in the unanesthetized animals. There was no significant difference in plasma norepinephrine and epinephrine levels between the 3 groups of rats. Plasma NPY levels were the lowest (65.4 +/- 8.8 fmol/ml, n-10, Mean +/- SEM) in salt-restricted and the highest (151.2 +/- 25 fmol/ml, n-14, p less than 0.02) in salt-loaded animals. Intermediate values were obtained in rats kept on a regular sodium intake (117.6 +/- 20.1 fmol/ml). These findings are therefore compatible with the hypothesis that sodium balance might to some extent influence blood pressure regulation via changes in circulating NPY levels which in turn modify blood pressure responsiveness.