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Metabolic syndrome (MetS) is highly correlated with cardiovascular diseases. Although an excess of body fat is a determinant factor for MetS development, a reduced level of testosterone plays a fundamental role in its regulation. Low testosterone level is highly related to insulin resistance, visceral obesity and MetS. We have searched in Pubmed clinical trial with the password: testosterone and insulin resistance, and testosterone and MetS. We found 19 studies on the correlation between testosterone level with insulin resistance and 18 on the effect of testosterone therapy on MetS. A high correlation between low testosterone and insulin resistance has been found in men, but not in women. Testosterone administration in hypogonadal men improved MetS and reduced the mortality risk. Androgen and oestrogen receptors are expressed in adipocytes, muscle and liver tissue, and their activation is necessary to improve metabolic control. Normalization of testosterone level should be the primary treatment in men, along with caloric restriction and physical exercise. These findings come mainly from correlative data, and there remains a need for randomized trials to strengthen this evidence. This review will consider the effects of testosterone on the regulation and development of MetS in men and women.

Left displacement of the abomasum (LDA) is a frequent disease in Holstein-Friesian cattle with a big economic impact in dairy farms. LDA is a multi-factorial disease and genetics is known to play a role (low to moderate estimated heritability). It is therefore of interest to look for genetic polymorphisms associated with LDA in order to find involved genes and clarify the pathogenesis of the condition. In a population of 62 Italian Holstein-Friesian cows, LDA cases and SNP genotypes were recorded, and a genome-wide association study (GWAS) was performed. A genetic signal of association with LDA was detected on BTA 12, within the sequence of the SLITRK5 gene. This gene is involved in neurological activities such as axonogenesis and synaptic transmission, and this may be related with abomasal hypomotility and atony, which are considered the primary causes of LDA. The results of this research suggest a role for the SLITRK5 gene, and more generally for all nearby genes of the SLITRK family, in the pathogenesis of LDA in dairy cattle. The involvement of the SLITRK gene family may lead to novel approaches for the prevention, diagnosis and therapy of LDA, and could also be used in enhanced selection schemes for healthier animals. © 2014 Elsevier B.V.

Immunoglobulin transfusion is employed in the management of the failure of passive transfer (FPT). The aim of this study was to investigate the dose of immunoglobulin G (IgG) needed to reach a protective concentration (>10 g/L) in colostrum-deprived dairy calves. Twenty-eight Holstein Friesian newborn male calves were randomly assigned to either a control group (CG) or a treatment group (PG). Calves in the CG received 4 L of high quality colostrum within 12 h of birth. Calves in the PG received 62.7 ± 3.1 g of IgG IV in 2.6 ± 0.3 L of plasma within 6 h after birth. Serum immunoglobulin G (sIgG) and serum total protein (sTP) concentrations were assayed before and after (24 h, 72 h and 1 week after birth) plasma transfusion or colostrum ingestion. Serum (s) IgG and sTP concentrations increased in both groups throughout the period of observation. Mean sIgG and sTP concentrations after colostrum ingestion or plasma transfusion were higher in the CG than in the PG (P < 0.01). Nine treated calves developed diarrhoea during the study and four were humanely euthanased due to progressive clinical deterioration. None of the calves in the CG showed signs of disease or died during the study. The dose of IgG used in this trial effectively provided an adequate sIgG concentration in colostrum-deprived calves (>10 g/L). Calves in the CG had significantly lower morbidity and mortality rates compared to those in the PG, suggesting that plasma transfusion alone is ineffective in providing complete protection against neonatal disease.

The aim of this work was to provide, for the first time, a protocol for isolation and characterization of stem cells from porcine amniotic membrane in view of their potential uses in regenerative medicine. From three samples of allanto-amnion recovered at delivery, the amniotic membrane was stripped from overlying allantois and digested with trypsin and collagenase to isolate epithelial (amniotic epithelial cells [AECs]) and mesenchymal cells, respectively. Proliferation, differentiation, and characterization studies by molecular biology and flow cytometry were performed. Histological examination revealed very few mesenchymal cells in the stromal layer, and a cellular yield of AECs of 10 × 10(6)/gram of digested tissue was achieved. AECs readily attached to plastic culture dishes displaying typical cuboidal morphology and, although their proliferative capacity decreased to the fifth passage, AECs showed a mean doubling time of 24.77 ± 6 h and a mean frequency of one fibroblast colony-forming unit (CFU-F) for every 116.75 plated cells. AECs expressed mesenchymal stem cell (MSC) mRNA markers (CD29, CD166, CD90, CD73, CD117) and pluripotent markers (Nanog and Oct 4), whereas they were negative for CD34 and MHCII. Mesodermic, ectodermic, and endodermic differentiation was confirmed by staining and expression of specific markers. We conclude that porcine amniotic membrane can provide an attractive source of stem cells that may be a useful tool for biomedical research.

Atresia ani, a congenital anomaly of the anus, can be associated with other types of malformation. Two female Holstein Friesian calves had imperforate anus, rectovaginal fistula, and perineal choristomas. In one case, the choristoma was composed of mature adipose and fibrous tissue with nephrogenic rests. In the other calf, the choristoma consisted of fragments of trabecular bone coated by cartilage and containing marrow, mixed with mature adipose and fibrous tissue, striated muscle fibers, nerves, and vessels. This combination of malformations resembles the association of anorectal malformations and perineal masses in children.

INTRODUCTION: Effects of postresuscitation treatment with argon on neurologic recovery were investigated in a porcine model of cardiac arrest (CA) with an underlying acute myocardial infarction. METHODS: The left anterior descending coronary artery was occluded in 12 pigs, and CA was induced. After 8 min of untreated CA, cardiopulmonary resuscitation was performed for 5 min before defibrillation. Following resuscitation, animals were subjected to 4-h ventilation with 70% argon/30% oxygen or 70% nitrogen/30% oxygen. Myocardial function was echocardiographically assessed, and serum neuron-specific enolase was measured. Animals were observed up to 72 h for assessment of survival and neurologic recovery. RESULTS: All the animals were resuscitated and survived for 72 h, except for a control pig. Ventilation with argon did not have any detrimental effects on hemodynamics and respiratory gas exchange. All the six argon-treated animals had a fast and complete 72-h neurologic recovery, in contrast to only two of the six controls (P < 0.05). Seventy-two-hour neurologic alertness score and neurologic deficit score were, respectively, 100 and 0 in the argon group and 79 and 29 in the control one (P < 0.01 and P < 0.05). Significantly lower increases in serum neuron-specific enolase (12% vs. 234%) and minimal histological brain injury (neuronal degeneration: 0 vs. 1) were also observed in argon-treated animals, in comparison to controls. CONCLUSIONS: In this model, postresuscitation treatment with argon allowed for a faster and complete neurologic recovery, without detrimental effects on hemodynamics and respiratory gas exchanges.

Three children with acquired immunodeficiency syndrome (AIDS) and chronic anaemia and leucopenia were treated with 5 μg/kg recombinant granulocyte colony-stimulating factor subcutaneously three times a week and 50 IU/kg erythropoietin subcutaneously twice a week. The therapy was not interrupted during the follow-up period. All children showed an increase of leukocyte count and haemoglobin levels. No transfusion was necessary and the number of admissions into hospital fell. These results suggest that combined therapy with granulocyte colony-stimulating factor and erythropoietin may improve leukopenia and anaemia, which is not zidovudine-related, in children who have AIDS.

A study was carried out in five children with acquired immune deficiency syndrome to assess the effect of combined zidovudine/interferon-α2a therapy with that of zidovudine given alone on immunological profiles and plasma zidovudine concentrations. Immunoglobulins A, G and M, total and absolute CD4 lymphocyte counts, and p24 antigen concentrations did not differ significantly when children were treated with 300 mg/m2 zidovudine given orally once every 12 h, or with 150 mg/m2 zidovudine plus 1.5 or 3 MIU interferon-α2a given intramuscularly three times weekly. Peak plasma zidovudine concentrations were significantly ( P < 0.05) lower when combined treatment with 150 mg/m2 zidovudine/1.5 MIU interferon-α2a was administered compared with 300 mg/m2 zidovudine alone, or combined 150 mg/m2 zidovudine/3 MIU interferon-α2a The results suggest that combination zidovudine/interferon-α2a therapy may be more efficacious than zidovudine alone and that the normal zidovudine dose may be reduced if interferon-α2a is given in addition, thus reducing the side-effects associated with zidovudine.

Cytokine-mediated communication between the immune system and the nervous system has been shown in the past few years. The precise cellular sources of these molecules in the brain is still a controversial issue. We have thus immortalized primary cell cultures from mouse embryonic brains to analyze cloned cells involved in cytokine production. The cell clones obtained were identified as microglial cells and shown to produce several monokines. Among these, TNF alpha was detected by molecular analysis and cytotoxicity assays and shown to be expressed by microglial cells, after activation with LPS. Surprisingly, the TNF alpha-mediated cytotoxic activity, which was neutralized by specific antisera, was not detected in the cell supernatants but was mediated through cell-to-cell contact. Using antibodies to TNF alpha in FACS analysis, specific cell membrane staining on live microglial cells was shown. The results suggest that in the brain the form of TNF alpha detectable by standard procedures is the cell bound form and not the most common form, secreted TNF alpha. In addition, the effects of recombinant TNF alpha in vitro and in vivo were evaluated. In vitro, rTNF alpha stimulated beta-endorphin, GH, and PRL release from cultured cells prepared from rat anterior pituitary glands. In vivo, the administration of rTNF alpha to rats was able to modify analgesic responses. The concomitant administration of naloxone, an opiate receptor antagonist, or monoclonal anti-IL-1 antibody decreased the analgesic effects induced by rTNF alpha. This indicates that the analgesic effect might not be mediated directly by rTNF alpha but by other mediators, whose action is under the control of TNF alpha.

Ghrelin, an acylated peptide produced predominantly by the stomach, has been discovered to be a natural ligand of the growth hormone secretagogue receptor 1a (GHS-R1a). It is localized in distinct cells of the gastric mucosa, mainly distributed in the mid portion of the oxyntic gland characterized by P/D1 granules in man and X/A-like granules in rodents. The ghrelin cell represents the second most frequent endocrine cell type after the enterochromaffin-like cells in gastric oxyntic mucosa, pointing to a potentially relevant role in the physiology of the stomach. Ghrelin has no relevant homology with any known gastrointestinal peptide and displays strong GH-releasing activity both in animals and in humans. However, in addition to stimulating GH secretion, ghrelin possesses several other endocrine and extraendocrine biological activities that are explained by the widespread distribution of ghrelin and GHS-R1a expression. In the rat, ghrelin exerts a control in gastric acid secretion and motility: the gastric acid secretion is stimulated by peripheral administration of high doses of ghrelin, but inhibited by very low doses of ghrelin delivered into the central nervous system. Moreover, ghrelin provides a potent and dose-related gastroprotective action against ethanol- and stress-induced gastric ulcers. The integrity of both nitric oxide (NO) system and capsaicin afferent nerves are required for the gastroprotective effect of ghrelin, whereas the vagus nerve might be involved in conveying ghrelinergic signal from periphery to the brain. In addition, prostaglandins derived by the constitutive cyclooxygenase (COX) activity are essential for the protective activity of ghrelin in ethanol and stress-induced gastric lesions. Given its prevailing role in physiological and pathophysiological gastric function, the discovery of ghrelin will open new perspectives and potential clinical implications in the gastroenteric field.

Ghrelin is an acylated peptide recently isolated from rat and human stomach that potently stimulates GH release in vivo and in vitro in rats and humans. Ghrelin specifically activates the receptor for the growth hormone secretagogues (GHS) and it has been proposed that it may be the endogenous ligand mimicked by these synthetic compounds. Ghrelin is primarily produced in endocrine cells of the stomach, and to a lesser extent, in other peripheral tissues, including the pituitary. Although ghrelin is the most potent GH-secretagogue so far identified, its circulating levels do not correlate with those of GH either in physiological and pathological conditions. Because of these and many other observations, it may be postulated that ghrelin is not physiologically involved in the regulation of growth hormone secretion. Nonetheless, ghrelin may serve as a very useful model for the development of more potent synthetic GHS, which may be therapeutically useful for the treatment of human GH deficiency.

The possibilities and the limits of texture analysis by NMR imaging using automatic discrimination algorithms, were investigated. The authors tried to identify objective descriptors of tissue textures by means of computerized analysis of gray level geometric properties. The algorithms were able to distinguish different tissues without reference to their anatomic location. Tissue structure could be characterized even before a clear macroscopic derangement has occurred. >

We previously reported that induction of selective GH deficiency in the rat exacerbates cardiac dysfunction induced by experimental ischemia and reperfusion performed on the explanted heart. In the same model, short-term treatment with hexarelin, a GH-releasing peptide, reverted this effect, as did GH. To ascertain whether hexarelin had non-GH-mediated protective effects on the heart, we compared hexarelin and GH treatment in hypophysectomized rats. Hexarelin (80 microg/kg sc), given for 7 days, prevented exacerbation of the ischemia-reperfusion damage induced by hypophysectomy. We also demonstrate that hexarelin prevents increases in left ventricular end diastolic pressure, coronary perfusion pressure, reactivity of the coronary vasculature to angiotensin II, and release of creatine kinase in the heart perfusate. Moreover, hexarelin prevents the fall in prostacyclin release and enhances recovery of contractility. Treatment with GH (400 microg/kg sc) produced similar results, whereas administration of EP 51389 (80 microg/kg sc), another GH-releasing peptide that does not bind to the heart, was ineffective. In conclusion, we demonstrate that hexarelin prevents cardiac damage after ischemia-reperfusion, and that its action is not mediated by GH but likely occurs through activation of specific cardiac receptors.

It is now an indisputable concept that the secretion of growth hormone (GH) is regulated by the central nervous system (CNS). Two specific hypothalamic neuropeptides, GH-releasing hormone (GHRF) and somatostatin (SRIF), control in an opposite way the pituitary somatotrophs and are the final mediators of the neural, hormonal, metabolic and environmental stimuli that affect GH secretion. GHRF and SRIF are in turn regulated by numerous neurotransmitters whose dual effect on GH secretion can be explained by the action of the same molecule either at the level of GHRF- or SRIF-secreting neurons (Fig. 1). This is well exemplified by catecholamines, where α2 and α1-β2 adrenoceptors exert respectively stimulatory and inhibitory influences on GH secretion (Muller et al. 1991).

Extensive research over the last 20 years has shown that in addition to classic hypothalamic regulatory hormones (RHs) (Table 1), a variety of other peptides exist in the central nervous system (CNS) of mammals.

A new statistical approach has been introduced to study in a quantitative way the coexistence of two neuromodulators in nerve cell bodies. The method has been exemplified on the ACTH-like and β-endorphin-like immunoreactive nerve cell bodies of the mediobasal hypothalamus demonstrated by means of indirect immunofluorescence methodology. The method is based on the analysis of 3 adjacent sections which, in a random way, are stained with antiserum against neuromodulator l. against neuromodulator 2 and with antisera against both neuromodulator 1 and neuromodulator 2. It could be shown that some neurons of the mediobasal hypothalamus do not contain at a detectable level both ACTH- and β-endorphin-like immunoreactivity. The present method also involves an analysis of the two nerve cell groups by means of a morphometric procedure to collect additional information on the extent of coexistence. Thus, by this approach the gravity centers of the two cell groups can be calculated. The distances between the two gravity centers of the ACTH and β-endorphin positive cell groups were significantly different at certain levels. The present method offers unique possibilities in increasing our understanding of the functional significance of coexistence of neuromodulators in one and the same nerve cell body since it makes possible a quantitative evaluation of coexistence. The usefulness of the present method is illustrated by the findings of a possible differential synthesis of ACTH- and β-endorphin-like material in certain cell bodies of the mediobasal hypothalamus.

Renin-like immunoreactivity could be demonstrated in the nuclei paraventricularis, periventricularis and supraopticus of the hypothalamus and in the cerebellar cortex of rats and mice, with both the peroxidase-antiperoxidase (PAP) and fluorescence techniques. The findings are consistent with the assumption of an endogenous angiotensin-forming system in the brain.

Linear contrast echo configuration on the pulmonary valve M-mode echogram was assessed in 28 patients with pulmonary hypertension, in 10 with pulmonary regurgitation, and in 10 normal subjects. Contrast echo parallel lines filling the total systolic phase of the pulmonary valve were recorded in normal subjects. Contrast echo lines stopping in early systole around the pulmonary valve mid-systolic notch were seen in all the patients with pulmonary hypertension in relation to changes with the pulmonary flow. Contrast echo lines reversing the early diastole and crossing the pulmonary valve echogram during diastole were detected in all the patients with pulmonary regurgitation, consistent with the reversed flow across the valve. The use of contrast echocardiography to diagnose both pulmonary hypertension and regurgitation may provide further useful information, particularly when the orientation and time of appearance of the contrast echo lines are related to the systolic and/or diastolic phases of the pulmonary valve M-mode echogram.

To obtain information on normal left ventricular activation, endocardial recordings with an electrode catheter were made a seven left ventricular sites in ten patients undergoing diagnostic heart catheterization. All the patients had: 1) sinus rhythm; 2) normal duration and shape of the QRS complex of left chest leads; 3) normal left ventriculography, i.e. normal volume and contractility of the left ventricle. The earliest left ventricular endocardial activation was recorded at septal and/or posterior level, i.e. at the septum (6 to 16 msec, average 9.7 msec, after the onset of intracardiac QRS complex) in seven patients; at the posterior wall (0 to 4 msec, average 2.6 msec, after the onset of intracardiac QRS complex) in three patients (in one of these, the earliest activation occurred at the posterior wall and apex simulaneously). If the earliest activation occurred at the left interventricular septum, the next excited point was found on the posterior wall or at the apex, and vice versa. The latest part to be activated was on the lateral free wall in seven patients; on the posterior wall in two patients; at the apex in the last one.

M-mode and two-dimensional subcostal contrast echocardiography were used in 67 patients and 10 normal subjects to evaluate the contrast echo effect on the inferior vena cava echogram in relation to the cardiac cycle and respiratory events. No contrast echoes were recorded in the inferior vena cava in normals during normal breathing. Contrast echoes were recorded entering the inferior vena cava in systole in 20 patients with tricuspid regurgitation and in pre-systole in patients with atrial septal defect and left-to-right shunt and in some of the patients with elevated right atrial and ventricular end-diastolic pressure. Forced inspiration increased the contrast echo effect and determined the penetration of microbubbles into the inferior vena cava. This latter feature occurred in all the patients and only in 1 normal subject. The entry of the contrast echoes into the inferior vena cava was attributed to the high right atrial ventricular end-diastolic pressure and to the reversed flow, from the right ventricle to the right atrium and inferior vena cava in tricuspid regurgitation and from the left atrium to the inferior vena cava in atrial septal defect. The contrast echocardiographic diagnosis of tricuspid regurgitation appeared to be most reliable. New encouraging results were obtained by this technique in diagnosing atrial septal defect and left-to-right shunt. The first appearance of the contrast, the time of appearance in relation to the cardiac cycle and the direction of the to and fro motion of contrast echoes were the most important factors considered for a correct diagnosis.

A 34-year-old woman without heart disease had an acute pulmonary edema after a grand mal seizure. Neurogenic pulmonary edema is characterized by the primary role played by the central nervous system in its pathogenesis, usually in the absence of cardiopulmonary disease. We believe that the initiating mechanism was a marked, although brief, generalized vasoconstriction, followed by a shift of blood from the peripheral vascular bed to the pulmonary vascular bed. We stress the need of treating the underlying neurologic disease as the only regional way of preventing the recurrence of pulmonary edema.

Twelve patients with dilated cardiomyopathy were studied in order to evaluate whether the favourable effect of Nifedipine on the right heart is due to a direct action of the drug on pulmonary resistances or is related to an improvement of left ventricular function. Echocardiographic examination of left and right heart was performed at basic conditions, after Nifedipine treatment--20 mg sublingually--and after 20 minutes of oxygen breathing (FiO2 75%). This was done in order to verify if oxygen vasodilating action could potentiate the Nifedipine effect. Echocardiographic date were obtained in basic conditions, 10, 20 and 30 minutes after Nifedipine and immediately after oxygen breathing. Ten normal subjects were used for comparison for basic data. Peak Nifedipine activity was observed 10 minutes after administration. At this time inferior vena cava emptying index and systolic pulsation were significantly increased, whereas left and right ventricle isometric contraction time, left and right ventricle ejection time, left and right ventricle isovolumetric relaxation time, end-diastolic left ventricular diameter, inferior vena cava diameters and systolic blood pressure had decreased, thus showing the favourable effect of Nifedipine of both heart sides. Heart rate did not significantly change. Oxygen inhalation induced a significant decrease of right ventricular isovolumetric relaxation and an increase of the inferior vena cava indexes, suggesting an improvement in right heart function, without any change in other parameters. No significant difference was found between data after-oxygen and data obtained 10' after Nifedipine, showing that the Nifedipine effect was not potentiated by oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

We administered growth-hormone releasing hormone (GHRH), clonidine or thyrotropin-releasing hormone (TRH) as intravenous boli each in three different randomized mornings to nine well-controlled Type 1 diabetic men and to six age-matched healthy men who served as controls. GHRH and clonidine evoked a prompt and brisk GH release both in diabetic and in control subjects with no significant difference being evident between the two groups. Only one diabetic subject showed a paradoxical GH release after TRH when he was under long-term poor metabolic control. These results indicate that in insulin-dependent patients with good control of the metabolic disease the response of somatotropes to pituitary- or central nervous system-directed stimuli is normal. These data are supportive of the idea that altered GH secretion in Type 1 diabetes rather than reflecting a primary hypothalamic and/or pituitary alteration may be a state-dependent phenomenon related to the metabolic state of the disease.

Weak to strong gastrin releasing peptide--bombesin (GRP-Bn)-like immunoreactivity was found in fine varicose nerve terminal systems of low to high densities in several parts of the CNS. The highest densities of strongly immunoreactive terminals were found in the marginal layer and in the substantia gelatinosa of the spinal cord, and in parts of the nuc. tractus spinalis nervi trigemini. Morphometrical analysis in the spinal cord demonstrates that GRP-BN-like-immunoreactive and substance P (SP), but not somatostatin (SS)-immunoreactive nerve terminals strikingly codistribute. Coexistence of SP and GRP-BN-like immunoreactivities was demonstrated in trigeminal and spinal ganglion nerve cells. Thus, GRP-BN-like immunoreactivity may coexist with SP in certain SP-immunoreactive nerve terminal systems.

Endogenous opioid peptides have a tonic inhibitory control on LH secretion, participating in the functional changes of the hypothalamic-pituitary-ovarian axis. To evaluate the activity of the endogenous opioid systems during the oestrous cycle, we measured plasma LH levels after naloxone administration (5 mg/kg, s.c.) at 09.00 and 16.00 h on all days of the cycle (two further measurements were taken at 14.00 and 18.00 h on the day of pro-oestrus) and after one dose or one week's treatment with oestradiol benzoate (OB; 0·2 μg/rat). Concentrations of LH were measured in the same experimental models after injection of LH-releasing hormone (LHRH; 1 μg/kg, i.p.) or saline. Naloxone induced a significant rise in LH levels on the day of oestrus, dioestrus day-1 and dioestrus day-2; this response was blunted on the morning of pro-oestrus and absent in the afternoon and after acute and chronic OB treatment. Conversely LHRH was most effective in increasing LH levels on the day of pro-oestrus and in OB-treated rats. These results indicate that opioid mechanisms, independently of the time of day and the pituitary responsiveness, exhibit a reduced activity when preovulatory changes occur, probably as a result of increased oestrogen levels. J. Endocr. (1986) 108, 89–94