Borolatonin limits cognitive deficit and neuron loss while increasing proBDNF in ovariectomised rats.

BACKGROUND: Borolatonin is a potential therapeutic agent for some neuronal diseases such as Alzheimer's disease (AD). Its administration exerts ameliorative effects such as those induced by the equimolar administration of melatonin in behavioral tests on male rats and in neuronal immunohistochemistry assays. OBJECTIVE: In this study, motivated by sex differences in neurobiology and the incidence of AD, the ability of borolatonin to induce changes in female rats was assessed. METHODS: Effects of borolatonin were measured by the evaluation of both behavioral and immunohistopathologic approaches; additionally, its ability to limit amyloid toxicity was determined in vitro. RESULTS: Surprisingly, behavioral changes were similar to those reported in male rats, but not those evaluated by immunoassays regarding neuronal survival; while pro-brain-derived neurotrophic factor (BDNF) immunoreactivity and the limitation of toxicity by amyloid in vitro were observed for the first time. CONCLUSION: Borolatonin administration induced changes in female rats. Differences induced by the administration of borolatonin or melatonin could be related to the differences in the production of steroid hormones in sex dependence. Further studies are required to clarify the possible mechanism and origin of differences in disturbed memory caused by the gonadectomy procedure between male and female rats.

Global longitudinal strain is superior to ejection fraction for detecting myocardial dysfunction in end-stage renal disease with hyperparathyroidism.

BACKGROUND: The estimation of left ventricular ejection fraction (LVEF) by 2D echocardiography (2D-ECHO) is the most used tool to assess LV systolic function (LVSF). Global longitudinal strain (GLS) has recently been suggested as a superior method for several evaluations. This study explored the association and prevalence of LV systolic dysfunction (LVSD) by using these methods in patients with end-stage renal disease (ESRD) and severe hyperparathyroidism (SHPTH); both associated with cardiovascular events (CEs). AIM: To evaluate the myocardial function in patients with ESRD and SHPTH by using the GLS and LVEF measured through conventional 2D-ECHO. METHODS: In 62 patients with ESRD and SHPTH, asymptomatic, and without a history of CEs, LVSF was evaluated by 2D-ECHO, obtaining the EF, by the Simpson biplane method, and GLS by speckle tracking. RESULTS: The total patients with ESRD had a preserved LVEF (> 50%) but abnormal GLS (< 13.55%). Additionally, multivariate analysis showed an independent association of GLS and serum parathyroid hormone (PTH), LV mass index, and hemoglobin. Also, PTH was independently associated with lateral e' wave and tricuspid regurgitation velocity. CONCLUSION: In patients with SHPTH linked to ESRD, the use of GLS by 2D-ECHO is a more sensitive tool than LVEF for detecting LVSD.

Synthesis, In Silico, and Biological Evaluation of a Borinic Tryptophan-Derivative That Induces Melatonin-like Amelioration of Cognitive Deficit in Male Rat.

Preclinical and clinical evidence supports melatonin and its analogues as potential treatment for diseases involving cognitive deficit such as Alzheimer's disease. In this work, we evaluated by in silico studies a set of boron-containing melatonin analogues on MT1 and MT2 receptors. Then, we synthesized a compound (borolatonin) identified as potent agonist. After chemical characterization, its evaluation in a rat model with cognitive deficit showed that it induced ameliorative effects such as those induced by equimolar administration of melatonin in behavioral tests and in neuronal immunohistochemistry assays. Our results suggest the observed effects are by means of action on the melatonin system. Further studies are required to clarify the mechanism(s) of action, as the beneficial effects on disturbed memory by gonadectomy in male rats are attractive.

Monoamines and their Derivatives on GPCRs: Potential Therapy for Alzheimer's Disease.

Albeit cholinergic depletion remains the key event in Alzheimer's Disease (AD), recent information describes stronger links between monoamines (trace amines, catecholamines, histamine, serotonin, and melatonin) and AD than those known in the past century. Therefore, new drug design strategies focus efforts to translate the scope on these topics and to offer new drugs which can be applied as therapeutic tools in AD. In the present work, we reviewed the state-of-art regarding genetic, neuropathology and neurochemistry of AD involving monoamine systems. Then, we compiled the effects of monoamines found in the brain of mammals as well as the reported effects of their derivatives and some structure-activity relationships. Recent derivatives have triggered exciting effects and pharmacokinetic properties in both murine models and humans. In some cases, the mechanism of action is clear, essentially through the interaction on G-protein-coupled receptors as revised in this manuscript. Additional mechanisms are inhibition of enzymes for their biotransformation, regulation of free-radicals in the central nervous system and others for the effects on Tau phosphorylation or amyloid-beta accumulation. All these data make the monoamines and their derivatives attractive potential elements for AD therapy.

Profile of three boron-containing compounds on the body weight, metabolism and inflammatory markers of diabetic rats.

It has been reported that boron induces changes in carbohydrate and lipid metabolism, body weight and inflammatory processes. This is relevant to the biomedical field due to the requirement for developing therapeutic tools with potential application in metabolic disorders affecting humankind. However, most of the reported data from both humans and animals were obtained after boron was administered as borax or boric acid. In this work, we determined the effects of boric, cyclohexylboronic (CHB) and phenylboronic (PBA) acids (10 mg/kg of body weight/daily for two weeks) on the body weight, metabolism and inflammatory markers in the blood of control, fat-feeding and experimental diabetic rats. In particular, we observed the effects of the administration of these compounds on glycaemia and cholesterol, triglyceride, insulin, IL-6 and C-reactive protein levels, as well as visceral fat and body weight. We found different profiles for each boron-containing compound: boric acid induced decreasing body weight, insulin and IL-6 levels; CHB administration induced an increase in body weight and cholesterol but decreased IL-6 levels; and PBA administration induced a decrease in visceral fat and glucose and insulin levels. These results can improve the understanding of boron as a metabolic regulator and help develop new potential strategies to use compounds with this trace element for therapeutic purposes.

Relationship of receptors of adipokines with hypertension and obesity. Murine model

Background: The aim of this paper is to investigated the contribution of adipose tissue thought the adipokines and kidney failure (KF) Methods: In male rats were fed with a standard lab diet (C) or a hypercaloric diet including 30% sucrose; obese group (Ob) and obese with kidney failure group (Ob/KF). We evaluated the changes of adipokines under conditions of obesity and KF, using 5/6 surgery to induce vascular injury. The anterior and media branches of the left kidney artery were tied together, leaving the posterior branch viable to enable the kidney to function. The right kidney was removed. Results: A 90% survival rate of the animals was achieved due to special care taken. Kidney function progressively decreased after surgery. Compared with the control group, in the other two groups (Ob and Ob/KF) the level of leptin increased and that of adiponectin decreased (p < 0.01). Post-surgery increases were observed in blood pressure, lipids, creatinine and insulin (p < 0.01). Conclusion: This model is proposed for the study pathophysiological mechanisms that lead to obesity and complications of kidney or cardiovascular function.

Introducción: El objetivo de este trabajo es investigar la contribución del tejido adiposo y las adipocinas y la insuficiencia renal (KF). Métodos: Ratas machos se alimentaron con una dieta estándar de laboratorio (C) o una dieta hipercalórica incluyendo 30% de sacarosa; Grupo obeso (Ob) y obeso con grupo de insuficiencia renal (Ob/KF). Se evaluaron los cambios de adipocinas en condiciones de obesidad y KF, utilizando cirugía 5/6 para inducir lesión vascular. Las ramas anterior y media de la arteria renal izquierda fueron unidas, dejando la rama posterior viable para permitir sobreviviencia y función renal. El riñón derecho fue removido. Resultados: Se logró una tasa de supervivencia del 90% de los animales debido a un cuidado especial. La función renal disminuyó progresivamente después de la cirugía. En comparación con el grupo control, en los otros dos grupos (Ob y Ob/KF) el nivel de leptina aumentó y el de adiponectina disminuyó (p < 0.01). Se observaron aumentos postquirúrgicos en la presión arterial, los lípidos, la creatinina y la insulina (p < 0.01). Conclusión: Este modelo se propone para el estudio de los mecanismos fisiopatológicos que conducen a la obesidad y las complicaciones de la función renal o cardiovascular.

Dopamine-dependent modulation of rat globus pallidus excitation by nicotine acetylcholine receptors.

The globus pallidus (GP) coordinates information processing in the basal ganglia nuclei. The contribution of nicotinic cholinergic receptors (nAChRs) to the spiking activity of GP neurons is largely unknown. Several studies have reported that the effect of nAChRs in other nuclei depends on dopaminergic input. Via in vivo single unit extracellular recordings and intranuclear drug infusions, we analyzed the effects of local activation and blockade of nAChRs in neurons of both sham and 6-hydroxydopamine (6-OHDA)-lesioned rats. In sham rats, the local application of nicotine and edrophonium (an acetylcholinesterase inhibitor) increases GP neurons spiking rate. Local application of mecamylamine, a neuronal nicotinic cholinergic antagonist, diminishes pallidal neurons spiking rate, an effect not produced by d-tubocurarine, a peripheral nicotinic cholinergic antagonist. Moreover, mecamylamine blocks the excitatory effect evoked by nicotine and edrophonium. In 6-OHDA-lesioned rats, local infusion of nicotine does not change pallidal neurons firing rate. Our results show that there is a tonic cholinergic input to the GP that increases their spiking rate through the activation of nAChRs and that this effect depends on functional dopaminergic pathways.