78 research outputs found

    Obesity-related to type-2 diabetes and brain cholinergic dysfunction: preliminary evidence from Obese Zucker Rats

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    Obesity is associated with glucose intolerance, type 2 diabetes, and dyslipidemia. Type-1 and type-2 diabetes are related with reduced performance on cognitive function likely depending by changes of the cholinergic system. The obese Zucker rats(OZRs), with leptin receptors mutation, represent a model of obesity related to type-2 diabetes. This study has investigated cholinergic system of OZRs compared with non-obese cohort lean Zucker rats(LZRs) to assess possible relationships between obesity and brain disorder. Male OZRs and LZRs of 16 weeks of age were used. Behavioural tests were performed to identify cognitive changes. Body weight, blood pressure and blood parameters were checked. The brain was processed for immunochemical and immunohistochemical analysis of neuronal specific nuclear protein (Neu-N), vesicular acetylcholine transporter (VAChT) and nicotinic(nAChR vertical bar vertical bar 7) were also evaluated. OZRs of different ages, showed body weight, systolic pressure, glycemia, insulin, triglycerides and cholesterol levels higher in comparison with LZRs. Behavioural tests revealed in OZRs non changes in anxiety and emotional learning tasks. In frontal cortex, morphological and immunochemical analysis revealed a decrease of Neu-N in OZRs compared to LZRs. In OZRs, a decrease of VAChT and nAChR square 7 immunoreaction was observed. These results may represent the first step to characterize neurological and cholinergic changes potentially occurring in brain of obese rats. This preclinical evidence may be useful to clarify the pathophysiology of brain damage reported in obese individuals

    Effect of Deoxamuscarine Etherification on M2 and M3 Muscarinic Affinity and Efficacy

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    A series of ether derivatives of deoxamuscarine were synthesized and tested for muscarinic activity on guinea-pig heart, ileum, and bladder. The results show that: a) The introduction ofthe benzyl group generates an agonist which is 5-fold more potent and 10-fold more selective than deoxamuscarine on ileum. This selectivity is ascribed to an increase of efficacy. b) Affinity and efficacy are differently affected by the substituents studied. c) The so-called muscarinic subsite interacting with the hydroxy group of muscarine-like compounds may acconìmodate bulky substituents, and on the basis of this new functionalized congeners may be designed with a view to achieving more potent and more selective muscarinic ligands

    Obesity-related to type-2 diabetes and brain cholinergic dysfunction: preliminary evidence from Obese Zucker Rats

    No full text
    Obesity is associated with glucose intolerance, type 2 diabetes, and dyslipidemia. Type-1 and type-2 diabetes are related with reduced performance on cognitive function likely depending by changes of the cholinergic system. The obese Zucker rats(OZRs), with leptin receptors mutation, represent a model of obesity related to type-2 diabetes. This study has investigated cholinergic system of OZRs compared with non-obese cohort lean Zucker rats(LZRs) to assess possible relationships between obesity and brain disorder. Male OZRs and LZRs of 16 weeks of age were used. Behavioural tests were performed to identify cognitive changes. Body weight, blood pressure and blood parameters were checked. The brain was processed for immunochemical and immunohistochemical analysis of neuronal specific nuclear protein (Neu-N), vesicular acetylcholine transporter (VAChT) and nicotinic(nAChR7) were also evaluated. OZRs of different ages, showed body weight, systolic pressure, glycemia, insulin, triglycerides and cholesterol levels higher in comparison with LZRs. Behavioural tests revealed in OZRs non changes in anxiety and emotional learning tasks. In frontal cortex, morphological and immunochemical analysis revealed a decrease of Neu-N in OZRs compared to LZRs. In OZRs, a decrease of VAChT and nAChR7 immunoreaction was observed. These results may represent the first step to characterize neurological and cholinergic changes potentially occurring in brain of obese rats. This preclinical evidence may be useful to clarify the pathophysiology of brain damage reported in obese individuals. Key words: Obesity, type-2 diabetes mellitus, brain cholinergic system

    Current pharmacological treatments for SARS-COV-2: A narrative review

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    The novel coronavirus, later identified as SARS-CoV-2, originating from Wuhan in China in November 2019, quickly spread around the world becoming a pandemic. Despite the knowledge of previous coronaviruses, such as those responsible for the SARS and MERS-CoV epidemic, there is no drug or prophylaxis treatment to this day. The rapid succession of scientific findings on SARS-CoV-2 provides a significant number of potential drug targets. Nevertheless, at the same time, the high quantity of clinical data, generated by a large number of rapidly infected people, require accurate tests regarding effective medical treatments. Several in vitro and in vivo studies were rapidly initiated after the outbreak of the pandemic COVID-19. Initial clinical studies revealed the promising potential of remdesivir that demonstrated a powerful and specific in vitro antiviral activity for COVID-19. Promising effects appear to be attributable to hydroxychloroquine. Remdesivir and hydroxychloroquine are being tested in ongoing randomized trials. In contrast, oseltamivir was not effective and corticosteroids are not currently recommended. However, few data from ongoing clinical trials are identifying low molecular weight heparins, innate immune system stimulating agents, and inflammatory modulating agents as potential effective agents. The authors assume that the current pandemic will determine the need for a systematic approach based on big data analysis for identifying effective drugs to defeat SARS-Cov-2. This work is aimed to be a general reference point and to provide an overview as comprehensive as possible regarding the main clinical trials in progress at the moment

    Telepediatric assistance in Iran: Specialist and subspecialty challenges

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    INTRODUCTION: Having justice for easy access to health services may probably be a standard feature and indisputable right of all health policies. The health policy of Iran enunciates this right. Unfortunately, as may happen in many countries, the execution of this policy depends on different factors. Among these parameters should be quoted as the suitable distribution of professionals, hospitals, and medical facilities. On the other hand, in Iran, there are many other problems linked to accessing areas with natural hindrances. OBJECTIVE: In this study, we analyzed the primary studies that report specialty and subspecialty challenges that had been faced by Iran to improve pediatric assistance. METHODS: Conduction of literature search in PubMed and CINAHL libraries was done, especially studies from 2010 to 2019. A Boolean operated ‘MeSH’ term was used for search. Newcastle–Ottawa Scale (NOS) scoring was adopted to assess the quality of each study. RESULTS: A total of 118 studies were displayed, and among them, 102 were excluded due to duplication and study relevance. Study selection was made based on its content were classified into two groups (1) shortage and unsuitable distribution of specialist and sub-specialist physicians in Iran, and (2) studies that explain the status of degradation in different areas of Iran. Outcomes demonstrated that Iran is generally suffering the shortage and unsuitable distribution of specialists and sub-specialists. This lack is particularly crucial in deprived and far-away areas from the cities. CONCLUSION: The present study analyzed in detail the current data regarding pediatric health services (specialist and subspecialty) and health-specific facilities distribution in the country

    Protective effect of treatment with nicardipine on cerebrovascular tree of spontaneously hypertensive rats.

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    The effect of an eight-week treatment with the Ca2+ channel blocker nicardipine on different-sized pial arteries and intracerebral arteries was assessed in spontaneously hypertensive rats (SHR) by microanatomical techniques. Normotensive Wistar-Kyoto (WKY) rats were used as normotensive reference animals. In SHR a significant increase of systolic blood pressure (SBP) in comparison with WKY rats was noticeable. An increased thickness of tunica media and luminal narrowing were also seen in medium- and small-sized pial arteries, and in intracerebral arteries of SHR in comparison with WKY rats. The media-to-lumen ratio was also increased in medium (diameter between 150 and 50 microm) and small-sized (diameter < than 50 microm) pial and intracerebral arteries. Treatment with nicardipine significantly reduced SBP, the thickness of tunica media, media-to-lumen ratio and increased luminal area of medium- and small-sized pial arteries and of intracerebral arteries. These findings demonstrate that treatment of SHR with nicardipine induces a moderate vasodilatation of both pial and intracerebral arteries regulating cerebrovascular resistance. This property may be useful in avoiding generalized or exaggerated cerebrovascular dilatation in hypertension which could be accompanied by impaired brain perfusion
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