Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 13, Issue 3, 2013

There is an increasing focus on diet as a tool to maintain human health and prevent disease. Milk and milk products of ruminants are important source of fat and saturated fatty acids, which are not considered to be very favourable to human health, but are valuable sources of nutrients including bioactive fatty acids (FA), vitamins, and minerals, which can promote positive health effects. The nutritional characteristics of milk and dairy products are related to their composition, which depends on the source species, and varies due to numerous factors, among which the animal diet is the most important. An improvement in milk FA composition and other micronutrients can be reached through an animal feeding strategy. Natural pasture-based farming systems increase microconstituents that are beneficial to human health (CLA, PUFAs, n-3 FAs, antioxidants, vitamins A and E, and Se) and volatile compounds (flavour, and terpenes) in milk and cheese. There are still uncertainties about the health benefits of various milk FAs and other compounds; deep and extensive long-term clinical studies with humans are needed. The contamination of milk and dairy products by heavy metals or dioxins has dramatic negative consequences for human and livestock health and necessitates very urgent consideration and intervention.

The obese Zucker rat (fa/fa) (ObZ) is a good animal model for Metabolic Syndrome (MS)-associated neuroendocrine and inflammatory disorders. The aim of the present investigation was to evaluate the effect of noradrenaline (NA) on the release of IL-1β, IL-6 and TNFα by macrophages from ObZ, as well as the effect of habitual exercise (running, 5days/week for 35 min at 35cm/s for 14week); all of them using lean Zucker rats (Fa/fa) (LZ) as reference values. Cytokines were determined by ELISA in the supernatants of macrophages cultured for 24h (37°C, 5% CO2 and 100% RH) in presence or absence of 10-5M NA. Both the spontaneous and NA-induced release of IL-1β and IL-6 were higher in sedentary obese (ObSZ) rats than in healthy LZ rats (a significant lower spontaneous production of TNFα was also found in the ObSZ rats). While the NA-induced release of IL-1β was higher in the exercised obese (ObTZ) rats, the NA-induced production of IL-6 was lower compared with ObSZ rats. In addition, NA has an inhibitory role on the release of IL-1β and TNFα (with respect to the spontaneous release) in both lean and obese (sedentary and exercised) rats. However, NA inhibits the IL-6 production by macrophages from lean and exercised obese animals, but promotes IL-6 release in the sedentary obese rats. In conclusion, an altered inflammatory response of macrophages mediated by NA is underlying in MS, and this regulation is improved after regular exercise, particularly on IL-6.

The present study evaluated the effect of nutritional imbalances during pregnancy, either by excess or deficiency, on fertility and conceptus development in obese-genotype swine (Iberian pig). Twenty-five multiparous sows were fed, from mating to farrowing, with a standard diet fulfilling either 1.6 folds their daily maintenance requirements for pregnancy (overfed group, n = 12) or only the 50% of such requirements (underfed group, n = 13). Ten out of 12 overfed but only two out of 13 underfed sows became pregnant (P<0.005). Fetal development was determined in the pregnant females at Days 35, 50, 75 and 90 of pregnancy. The embryos from undernourished sows were smaller than the embryos from overfed females as early as at 35 days of pregnancy (P>0.05) and remained smaller until Day 90 of gestation. However, at the end of pregnancy, there were significant changes in the developmental patterns of fetuses. Thus, weight and size of the offspring from both nutritional treatments were finally similar at delivery; the same was found at weaning. There was thereafter a sex-related effect on the growth during the early-postnatal period, with male piglets of both nutritional origins being significantly heavier and more corpulent at weaning that their sisters (P>0.05). In conclusion, fetal growth conditioned by malnutrition from periconceptional stages is mainly regulated at the end of the pregnancy, so that ensure an adequate body-weight and size and, therefore, the survival of the offspring. Afterwards, the early-postnatal development of the offspring is affected by sex, independently from nutritional origin, with male piglets growing faster than females.

In this review, we analyzed the role played by central and peripheral chemoreceptors (CHRs) in vasopressin (AVP) secretion control. Central neural pathways subserving osmotic and non-osmotic control of AVP secretion are strictly correlated to brain areas participating in chemoreception mechanisms. Among the different brain areas involved in central chemoreception, the most important site has been localized in the retrotrapezoid nucleus of the rostral ventrolateral medulla. These central CHRs are able to detect very small pH/CO2 fluctuations, participating in brain blood flow regulation, acid-base balance and blood pressure control. Decreases in arterial pH and increases in arterial pCO2 stimulate AVP release by the Supraoptic and Paraventricular Nuclei. Carotid CHRs transduce low arterial O2 tension into increased action potential activity, leading to bradycardia and coronary vasodilatation via vagal stimulation, and systemic vasoconstriction via catecholaminergic stimulation. Stimulation of carotid CHRs by hypoxia increases neurohypophyseal blood flow and AVP release, an effect inhibited by CHRs denervation. Two renal CHRs have been identified: Type R1 CHRs do not have a resting discharge but are activated by renal ischemia and hypotension; Type R2 CHRs have a resting discharge and respond to backflow of urine into the renal pelvis. Signals arising from renal CHRs modulate the activity of hypothalamic AVPergic neurons: activation of R1 and R2 CHRs, following increased intrapelvic pressure with solutions of mannitol, NaCl and KCl, produces a significant increase of AVP secretion and the same effect has been obtained by the intrarenal infusion of bradykinin, which excites afferent renal nerves, as well as by the electrical stimulation of these nerves.

Introduction: Diabetes mellitus has been linked to cognitive decrement faster than usual. Medical management of diabetes can also interfere with the cognitive skills. The purpose of this study was to evaluate the effects of vildagliptin on cognition, as an add-on to metformin therapy in elderly patients with type 2 diabetes mellitus. Materials and Methods: This was a prospective and observational investigation conducted in 10 elderly type 2 diabetes mellitus patients who were started treatment with vildagliptin 50 mg twice daily to ongoing metformin. All participants underwent detailed clinical cognitive assessment and neuropsychological testing with mini mental state examination (MMSE) and clock drawing test (CDT), along with measurement of functional parameters at entry and study completion. Results: Mean follow-up time was 10.9±3.7 months. No subjects reported significant side effects during the study. At follow-up, in accordance with the clinical assessment, neither MMSE nor CDT showed significant changes after addition of vildagliptin to metformin. Basic and instrumental activities of daily living (BADL and IADL), mini nutrition assessment and geriatric depression scale scores also remained unchanged between the two evaluations. Discussion: In this pilot study, addition of vildagliptin to ongoing metformin therapy in elderly with diabetes was accompanied by stable cognitive and functional performance after almost one year of follow-up.

Introduction: It has been approved that vitamin D deficiency has a role in increasing the rate of cardio-vascular diseases in diabetic patients with unknown mechanism. The effects of vitamin D on hemostasis and its inflammatory mechanisms have been proposed as possible causes of cardio-vascular diseases in these patients. Also, high level of plasminogen activator inhibitor- type 1 (PAI-1) has been identified as a risk factor for cardio-vascular diseases in diabetic patients. The goal of this survey was to investigate the relation between vitamin D level and level of PAI-1 as a thrombotic marker. Patients and Methods: 180 patients with type 2 diabetes mellitus enrolled for the study. The serum level of PAI-1 was measured by enzyme linked immune-assay and was compared with calcium metabolism markers including vitamin D, parathormon hormone, fasting blood sugar, calcium, and phosphorous. Results: There was statistically significant relation between PAI-1 with fasting blood sugar and high density lipoprotein, but there was no significant relation between PAI-1 with vitamin D level and other cardio-vascular disease variables. Discussion: It seems that serum level of vitamin D has no relation with PAI-1 in diabetic patients, although further investigations are required to confirm these findings.

Diabetes is now one of the most common un-communicable diseases worldwide. Few studies have dealt specifically with the potential therapeutic effect of TNF-α suppressor to decrease oxidative stress markers in patients with diabetes. The aim of this study was to investigate the potential therapeutic and toxic effect of the direct injection of the anti-TNF-α on oxidative stress mediators, proinflammatory cytokines and vascular risk factors associated with diabetes on diabetic rats. Methods: diabetes was induced by streptozotocin, three weeks after the – induction of diabetes, a polyclonal anti-mouse/rat TNF-α rabbit serum was injected in the treated group and sacrificed after 4 weeks. The expression of TNF-α mRNA was measured by RT-PCR. The levels of TNF-α, VEGF, IL-2, IL- 6, HSP-70, troponin-t, 8-OHdG, ICAM-1 and VCAM-1 were evaluated using ELISA. Myeloperoxiase (MPO) and total peroxides (TPs) levels were estimated by biochemical reactions. Results: the treatment of diabetic rats with the anti-TNF-α caused a significant decrease in the TNF-α mRNA expression, which were paralleled with the decreased levels of TNF-α, IL-6, MOP, HSP-70, ICAM-1, VCAM-1, troponin-t and 8-OHdG in the blood serum. On the contrary, all were highly expressed in the diabetic group that may be the leading reasons for the DNA damage and cell loss. Data revealed that TNF-α, HSP-70, IL-6, MPO and adhesion molecules when expressed in diabetic rats, collectively induce dramatic changes. Conclusion: these new findings suggested that targeting TNF-α could effectively reduce expressions of MCP-1, HSP-70, troponin-t, 8-OHdG and VCAM- 1, along with prominent reduction in MPO and IL-6 levels.

The clinical occurrence of ectopic thyroid gland is an infrequently encountered condition, resulting from a developmental abnormality during the migration of the thyroid anlage from the floor of the primitive foregut to its final position in the neck. It can be found along the way of thyroid descent, in the midline, or laterally in the neck or even in the mediastinum or under the diaphragm. This condition is often asymptomatic, whereas symptoms could be related to ectopic thyroid size, to its relationships with surrounding organs or to diseases affecting the ectopic thyroid in the same way they involve orthotopic glands. Sometimes, a growing mass can lead to the clinical suspicion of a tumor disease. On the other hand, thyroid ectopy must be distinguished from metastasis of thyroid cancer. Scintigraphy and ultrasonography are the main diagnostic means for evaluating ectopic thyroid tissue, whereas fine needle aspiration could be useful in the presence of a nodular ectopic gland or when the coexistence of an orthotopic thyroid can arise the suspicion of a metastasis from a thyroid cancer. Surgical removal is indicated in symptomatic cases, whereas radioiodine ablation is reserved to recurrent disease. In this paper we report an emblematic case of ectopic thyroid gland and a review of the literature dealing with this condition.