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Dysregulated cortical expression of the neural cell adhesion molecule (NCAM) and deficits of its associated polysialic acid (polySia) have been found in Alzheimer's disease and schizophrenia. However, the functional role of polySia in cortical synaptic plasticity remains poorly understood. Here, we show that acute enzymatic removal of polySia in medial prefrontal cortex (mPFC) slices leads to increased transmission mediated by the GluN1/GluN2B subtype of N-methyl-d-aspartate receptors (NMDARs), increased NMDAR-mediated extrasynaptic tonic currents, and impaired long-term potentiation (LTP). The latter could be fully rescued by pharmacological suppression of GluN1/GluN2B receptors, or by application of short soluble polySia fragments that inhibited opening of GluN1/GluN2B channels. These treatments and augmentation of synaptic NMDARs with the glycine transporter type 1 (GlyT1) inhibitor sarcosine also restored LTP in mice deficient in polysialyltransferase ST8SIA4. Furthermore, the impaired performance of polySia-deficient mice and two models of Alzheimer's disease in the mPFC-dependent cognitive tasks could be rescued by intranasal administration of polySia fragments. Our data demonstrate the essential role of polySia-NCAM in the balancing of signaling through synaptic/extrasynaptic NMDARs in mPFC and highlight the therapeutic potential of short polySia fragments to restrain GluN1/GluN2B-mediated signaling.
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Enfermedad de Alzheimer , Ratones , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Ácidos Siálicos/metabolismo , Cognición , Moléculas de Adhesión de Célula Nerviosa/metabolismo , Receptores de N-Metil-D-AspartatoRESUMEN
Breast cancer (BC) is one of the most prevalent cancers and the leading cause of cancer related deaths among women worldwide with a steadily increasing global annual incidence. This study aims is to evaluate the knowledge, attitude, and practice of females in the UAE toward BC and Breast Self-Examination practice in the seven Emirates. This was a face-to-face questionnaire-based study using CAM (Breast Cancer Awareness Measure) conducted over 3 months (from March to June 2019) on a random sample of females across the UAE. Of the 400 females who filled the questionnaire, 112 (28%) did the CBE at least once, and 184 (46%) practice BSE. Only 33% of participants were aware of the incidence of the BC in the UAE and those females were more likely to practice BSE (P < 0.05). In contrast, the majority showed a high awareness level in identifying cancer as a curable (91.5%) and non-transmittable (87%) disease that can be diagnosed at its earlier stages (93%). Only 11% of the participants identified weight reduction as a way to prevent BC. Knowledge of breast cancer sign/symptoms were good, as 41-87% of respondents were able to identify at least a single sign/symptom. The lack of awareness of BC among females in the UAE is of concern as it leads to low practices of screening and early detection, which ultimately will result in increased morbidity, mortality, and treatment costs. Further initiatives should be taken to increase practice, knowledge and awareness on early detection and screening for BC in the UAE community.
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Neoplasias de la Mama , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Autoexamen de Mamas , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Tamizaje Masivo , Encuestas y CuestionariosRESUMEN
Testosterone is the major male hormone produced by testicles which are directly associated with man's appearance and secondary sexual developments. Androgen deficiency starts when the male hormonal level falls from its normal range though, in youngsters, the deficiency occurs due to disruption of the normal functioning of pituitary, hypothalamus glands, and testes. Thus, testosterone replacement therapy was already known for the treatment of androgen deficiency with lesser risks of producing cardiovascular problems. Since from previous years, the treatment threshold in the form of testosterone replacement therapy has effectively increased to that extent that it was prescribed for those conditions which it was considered as inappropriate. However, there are some research studies and clinical trials available that proposed the higher risk of inducing cardiovascular disease with the use of testosterone replacement therapy. Thus under the light of these results, the FDA has published the report of the increased risk of cardiovascular disease with the increased use of testosterone replacement therapy. Nevertheless, there is not a single trial available or designed that could evaluate the risk of cardiovascular events with the use of testosterone replacement therapy. As a result, the use of testosterone still questioned the cardiovascular safety of this replacement therapy. Thus, this literature outlines the distribution pattern of disease by investigating the data and link between serum testosterone level and the cardiovascular disease, also the prescription data of testosterone replacement therapy patients and their tendency of inducing cardiovascular disease, meta-analysis and the trials regarding testosterone replacement therapy and its connection with the risks of causing cardiovascular disease and lastly, the possible effects of testosterone replacement therapy on the cardiovascular system. This study aims to evaluate the available evidence regarding the use of testosterone replacement therapy when choosing it as a treatment plan for their patients.
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Sistema Cardiovascular/efectos de los fármacos , Terapia de Reemplazo de Hormonas/efectos adversos , Testosterona/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Humanos , Masculino , PacientesRESUMEN
Background: Inflammation is a strong reaction of the non-specific natural immune system that helps to start protective responses against encroaching pathogens and develop typical immunity against intruding factors. However, prolonged inflammation may lead to chronic autoimmune diseases. For thousands of years, medicinal plants have served as an excellent source of treatment for chronic pathologies such as metabolic diseases. Purpose: The present study aims to evaluate the anti-inflammatory and anti-angiogenic potential of Moringa olifera Lam. extract (MO) and Moringa-loaded nanoclay films. Methods: The extract preparation was done through the maceration technique using absolute methanol (99.7%) and labelled as Mo. Me. Mo. Me-loaded nanoclay-based films were prepared by using pectin and sericin (Table 1). The in vitro studies characterized the film thickness, moisture, and phytochemical contents. The in vivo anti-inflammatory tests involved using a cotton pellet-induced granuloma model assay. In addition, the chick chorioallantoic membrane (CAM) assay was employed for angiogenesis activity. Results: The phytochemical analysis of the extract confirmed the presence of alkaloids, glycosides, flavonoids and phytosterol. This extract contained quercetin in a large quantity. Cotton-pellet induced granuloma model study revealed a comparable (p > 0.05) effect of a high dose of Mo. Me (500 mg/kg) as compared with standard drug. Noteworthy, data obtained through the RT-PCR technique manifested the dose-dependent anti-oedematous effect of Moringa olifera via downregulation of TNF-α and interleukin-1ß. The findings of the CAM assay exhibited a remarkable anti-angiogenic activity of Mo. Me loaded nanoclay films, showing diffused vasculature network in the macroscopic snapshot. Conclusion: Moringa olifera and its nanocomposite films have therapeutic potential against inflammation.
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Environmental pollutants present a potential source of toxicity when exposed to humans. The study was aimed at investigating the potential of Oligochaeta ramosa (Roxb.) as a hepatoprotective agent in cadmium-induced hepatotoxicity causing lipid profile disturbance. The aqueous methanolic (30 : 70 v/v) extract of O. ramosa Roxb. (AME.Or) was subjected to preliminary phytochemical analysis, whereas the antioxidant activity of its constituents was investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The hepatoprotective and antihyperlipidemic effects of AME.Or was investigated by dividing animals into five groups (A-E). Animals were either treated with normal saline or CdCl2 (6.5 mg/kg, intraperitoneally) followed by treatment with silymarin (100 mg/kg), or AME.Or (200 mg/kg) and AME.Or (400 mg/kg) for consecutive three weeks. Blood samples were collected, and the serum lipid profile was assessed on the 11th and 21st day of treatment. Histopathological analysis was performed after euthanization. In vitro analysis of AME.Or revealed 64% inhibition as free radicals scavenging potential during DPPH, total phenolic content (TPC) (79.92 mgGAE/g), and total flavonoids content (TFC) (38.75 mgRE/g). The group intoxicated with CdCl2 showed significantly high (p ≤ 0.05) levels of the liver function indicators and lipid profile than in the control group. The higher dose of AME.Or (400 mg/kg) significantly decreased the aspartate aminotransferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), total bilirubin (p ≤ 0.001), decreased total cholesterol and triglycerides (p ≤ 0.01) while significantly increased high density lipoprotein (HDL; p ≤ 0.01) as compared to the intoxicated group. The histopathological analysis of the liver revealed signs of necrosis in the intoxicated group, while AME.Or treated groups showed marked improvement. The findings accentuate the therapeutic importance of O. ramosa (Roxb.) as a hepatoprotective remedy.
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Background: The profession of pharmacy has evolved significantly in recent years in terms of professional service delivery. The aim of this study was to explore the current views of pharmacists in the United Arab Emirates (UAE) on pharmaceutical care services and the nature of barriers encountered in practice using qualitative and quantitative assessment methods. Methods: A cross-sectional study was conducted among hospital and community pharmacists (n = 305) between March and May 2021, using qualitative and quantitative assessment methods. In the qualitative phase, 15 interviews were conducted to explore five main criteria: patient information, inadequate patient counseling, prescribing errors prevention and identifying drug-related problems, lack of participation in health awareness programs, and barriers to pharmaceutical care implementation. In the quantitative phase, 305 consenting pharmacists completed a questionnaire on seven criteria: demographic profile, pharmacist-physician interaction, patient counseling assessment, patient reports of adverse drug events, pharmacist participation in health awareness programs, perceptions of reducing prescribing errors and identifying drug-related problems, and barriers to appropriate pharmaceutical care implementation. Results: The results of both the qualitative and quantitative phases of the study revealed that pharmacists' influence on practice in the UAE is limited due to many factors, mainly lack of time and patients' ignorance of the pharmacist's role in the medical field. The mean responses regarding pharmacists' approach to patient counseling and patients' knowledge of pharmacists' role in managing adverse drug reactions were 77.1% and 59.7%, respectively. Active participation in health awareness programs was 64.8%. The mean positive response of participants in reducing prescribing errors and recognizing drug-related problems was 9.2%. Pharmacists' age and number of years in practice were the most important factors influencing the pharmaceutical care services implementation. Conclusion: The study has shown the need to shed light on the proper implementation of pharmaceutical care while maintaining a trusting relationship with physicians.
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Servicios Farmacéuticos , Farmacéuticos , Humanos , Farmacéuticos/psicología , Emiratos Árabes Unidos , Estudios Transversales , Actitud del Personal de Salud , Rol Profesional , Relaciones Interprofesionales , HospitalesRESUMEN
Background: Caffeine is widely consumed among students due to its cognitive and physical enhancing effects. However, little is known about the consumption pattern of different caffeinated products among university students in the United Arab Emirates (UAE). Aim: To investigate the frequency of caffeine consumption among the young population of students, assess types of caffeinated products consumed, and document adverse effects and withdrawal symptoms experienced by university students. Methods: A cross-sectional study was conducted in the UAE from December 2019 to March 2020. A random sample of 500 university students from different universities in the UAE were approached and asked to complete a self-administered online-based questionnaire. Data were analyzed using the Statistical Package for Social Science (SPSS) version 26. Results: Of (n = 500) surveyed students, (n = 467) completed the survey 93.4%. The average level of caffeine consumption was significantly higher in females compared to male students (p < 0.005). Coffee was the highest favored source of caffeine (67.7%) followed by tea (47.3%). The average daily intake of caffeine was found to be 264 mg/day. Surprisingly, almost a third of students reported a high level of daily consumption (>400 mg/day) and more than half of them consumed less than 199 mg/day. Large proportions of students 91.1% have their caffeinated beverage after or while eating meals and 42.8% considered that this habit helped in avoiding acid reflux. Interestingly, around one third of participants have poor knowledge of caffeine-containing medical products, which seemed to affect the level of consumption in the student population (p < 0.05). The highest reported reason for caffeine intake was for studying purposes (59.4%). Conclusion: Caffeine consumption is highly prevalent among university students in the UAE. Yet, there is insufficiency in the current knowledge of safe caffeine consumption patterns reflecting the importance of health awareness programs and nutritional lectures to decrease the long-term health issues and unintentional overdose of caffeine.
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One of the standards for cancer treatment is cancer immunotherapy which treats both primary and metastasized tumors. Although cancer immunotherapeutics show better outcomes as compared with conventional approaches of cancer treatment, the currently used cancer immunotherapeutics have limited application in delivering cancer antigens to immune cells. Conversely, in solid tumors, tumor microenvironment suppresses the immune system leading to the evasion of anticancer immunity. Some promising attempts have been made to overcome these drawbacks by using different approaches, for instance, the use of biomaterial-based nanoparticles. Accordingly, various studies involving the application of nanoparticles in cancer immunotherapy have been discussed in this review article. This review not only describes the modes of cancer immunotherapy to reveal the importance of nanoparticles in this modality but also narrates nanoparticle-mediated delivery of cancer antigens and therapeutic supplements. Moreover, the impact of nanoparticles on the immunosuppressive behavior of tumor environment has been discussed. The last part of this review deals with cancer immunotherapy using a combination of traditional interventional oncology approach and image-guided local immunotherapy against cancer. According to recent studies, cancer therapy can potentially be improved through nanoparticle-based immunotherapy. In addition, drawbacks associated with the currently used cancer immunotherapeutics can be fixed by using nanoparticles.
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Inmunoterapia/métodos , Nanopartículas/uso terapéutico , Neoplasias/terapia , Animales , Antígenos de Neoplasias/metabolismo , Humanos , Inmunidad , Neoplasias/inmunología , Microambiente TumoralRESUMEN
Obesity linked diabetes, popularly known as diabesity, has been viewed as a direct product of the modern lifestyle in both developed and developing countries, and its increased prevalence is seen as a major threat to public health globally. Ficus carica (FC) and Syzigium cumini (SC) are part of indigenous flora with traditional medicinal properties. Fresh seeds of SC fruit and fruit of FC were collected and macerated to obtain the final extract. Wistar rats were divided into seven groups fed either on a normal diet or high-fat diet (HFD) along with streptozocin (STZ) to induce diabesity. The crude extract of FC (FC.Cr.) and SC (SC.Cr.) were administered at 250 mg/kg/day and 500 mg/kg/day in induced diabesity state. Body weights, blood glucose level, complete blood count (CBC), cholesterol, triglycerides (TG), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) were recorded to analyze their effects on glucose and lipid metabolism. Further, superoxide dismutase (SOD) and malondialdehyde (MDA) were measured to examine their effects on lipid peroxidation and ant oxidative enzyme. Results showed that both FC.Cr. and SC.Cr. have the potential to control obesity-linked type 2 diabetes mellitus (T2DM) by lowering the body weights, serum glucose, cholesterol, TG, LDL, and VLDL, while increasing the protective effects of HDL dose-dependently. The crude extract of both plants showed significant activity to raise SOD and curb MDA under diabetic states. It was concluded that both FC.Cr. and SC.Cr. exhibited remarkable therapeutics potential in HFD-STZ-induced diabetic rats. However, we found that the effects of SC.Cr. are relatively more pronounced as compared to FC.Cr. in almost all parameters.
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Glucemia/análisis , Diabetes Mellitus Experimental/tratamiento farmacológico , Dieta Alta en Grasa , Ficus/metabolismo , Lípidos/sangre , Myrtaceae/metabolismo , Animales , Glucemia/metabolismo , Peso Corporal , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/sangre , Hipoglucemiantes/farmacología , Metabolismo de los Lípidos , Peroxidación de Lípido , Estrés Oxidativo , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Estreptozocina , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: The metabolic syndrome increases the risk of different diseases such as type 2 diabetes. The prevalence of metabolic syndrome has rapidly grown and affected more than 230 million people worldwide. Viola odorata is a traditionally used plant for the treatment of diabetes; however, its mechanism to manage diabetes is still unknown. PURPOSE: This study was designed to systematically assess the mechanism of action of Viola odorata in diabetes. METHODS: An extensive literature search was made to establish an ingredient-target database of Viola odorata. Of these, targets related to diabetes were identified and used to develop a protein-protein interaction network (PPIN) by utilizing the STITCH database. The obtained PPIN was assessed through Gene Ontology (GO) enrichment analysis based on ClueGO plugin. RESULTS: According to the acquired data, there were about 143 chemical constituents present in Viola odorata having 119 protein targets. Of these, 31 targets were established to give the pharmacological effect against diabetes. The UniProt database was used for screening of 31 targets, out of which Homo sapiens contained 22 targets. Ultimately, 207 GO terms, grouped into 41 clusters, were found by gene analysis, and most of them were found to be linked with diabetes. According to findings, several proteins including TP53, BCL2, CDKN1A, 1L6, CCND1, CDKN2A, and RB1 have a significant role in the treatment of diabetes by Viola odorata. CONCLUSION: The possible activity of Viola odorata in the management of diabetes may be mediated by several molecular mechanisms, including the glutamine metabolic process, IRE1-mediated unfolded protein response, and pentose metabolic process.
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Diabetes Mellitus Tipo 2/metabolismo , Descubrimiento de Drogas/métodos , Extractos Vegetales/farmacología , Viola/química , Simulación por Computador , Humanos , Simulación del Acoplamiento Molecular , Mapas de Interacción de Proteínas/efectos de los fármacosRESUMEN
The skeletal system is fundamental for the structure and support of the body consisting of bones, cartilage, and connective tissues. Poor fracture healing is a chief clinical problem leading to disability, extended hospital stays and huge financial liability. Even though most fractures are cured using standard clinical methods, about 10% of fractures are delayed or non-union. Despite decades of progress, the bone-targeted delivery system is still restricted due to the distinctive anatomical bone features. Recently, various novel nanocomposite systems have been designed for the cell-specific targeting of bone, enhancing drug solubility, improving drug stability and inhibiting drug degradation so that it can reach its target site without being removed in the systemic circulation. Such targeting systems could consist of biological compounds i.e. bone marrow stem cells (BMSc), growth factors, RNAi, parathyroid hormone or synthetic compounds, i.e. bisphosphonates (BPs) and calcium phosphate cement. Hydrogels and nanoparticles are also being employed for fracture healing. In this review, we discussed the normal mechanism of bone healing and all the possible drug delivery systems being employed for the healing of the bone fracture.
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Remodelación Ósea/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Curación de Fractura/efectos de los fármacos , Fracturas Óseas/tratamiento farmacológico , Nanocompuestos/administración & dosificación , Animales , Cementos para Huesos/metabolismo , Remodelación Ósea/fisiología , Difosfonatos/administración & dosificación , Difosfonatos/metabolismo , Curación de Fractura/fisiología , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/metabolismo , Humanos , Hidrogeles/administración & dosificación , Hidrogeles/metabolismo , Nanopartículas/administración & dosificación , Nanopartículas/metabolismoRESUMEN
OBJECTIVE: The objective of this study was to assess the influence of enzyme suppression on the values of various pharmacokinetic factors of orally administered metoclopramide. METHOD: This study was conducted in two phases and a 4-week duration was adopted for drug washout. This randomized study involved 12 healthy human volunteers who received a single oral dose of metoclopramide 20 mg. After the washout period, volunteers received clarithromycin 500 mg two times per day for consecutive 5 days. On test day (fifth day), a single oral dose of metoclopramide 20 mg was also given to the volunteers, and collection of blood samples was conducted at pre-decided time points. Various pharmacokinetic parameters such as Cmax, Tmax, and AUC0-∞ of metoclopramide were determined by analyzing the blood samples using a validated HPLC-UV method. RESULTS: Clarithromycin increased the mean values of Cmax, AUC0-∞, and T1/2 of metoclopramide by 46%, 78.6%, and 9.8%, respectively. CONCLUSION: Clarithromycin noticeably increased the concentration of plasma metoclopramide. This study's results provide in vivo confirmation of the CYP3A4 involvement in metoclopramide metabolism, in addition to CYP2D6. Therefore, metoclopramide pharmacokinetics may be clinically affected by clarithromycin and other potent enzyme inhibitors.
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Antieméticos/farmacocinética , Claritromicina/farmacología , Inhibidores del Citocromo P-450 CYP3A/farmacología , Metoclopramida/farmacocinética , Administración Oral , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antieméticos/administración & dosificación , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Claritromicina/administración & dosificación , Citocromo P-450 CYP3A/efectos de los fármacos , Citocromo P-450 CYP3A/metabolismo , Inhibidores del Citocromo P-450 CYP3A/administración & dosificación , Interacciones Farmacológicas , Semivida , Humanos , Masculino , Metoclopramida/administración & dosificación , Adulto JovenRESUMEN
Frostbite is caused due to extreme vulnerability to cold, resulting in damage of deeper and superficial tissues alike. In this study, we report the anti-inflammatory and wound-healing properties of aqueous methanolic extract of Cuscuta reflexa (Cs.Cr) against contact frostbite. Thirty rats were divided into five groups including three treatment groups with increasing doses of Cs.Cr, a standard drug group receiving acetylsalicylic acid (ASA), and a metal bar-induced frostbite group. Frostbite injury was induced by a 3 × 3.5 cm metal bar frozen up to -79°C on shaved skin for continuous 3 minutes. Wounded area percentages were recorded to measure the healing rate in response to Cs.Cr administration. Haematological parameters and malondialdehyde content were also noted. On treatment with Cs.Cr, the healing rate is drastically increased and lipid peroxidation product malondialdehyde was decreased in a dose-dependent manner. Results were compared with frostbite and ASA (standard drug group). These results indicate that Cs.Cr possesses excellent wound-healing properties against frostbite injury and can prove to be a prospective compound in such conditions.
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Cuscuta , Congelación de Extremidades , Extractos Vegetales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Estudios Prospectivos , Ratas , Piel/efectos de los fármacos , Piel/patologíaRESUMEN
Leptin resistance and co-existing insulin resistance is considered as hallmark of diet-induced obesity. Here, we investigated therapeutic potential of hesperidin to improve leptin and insulin resistance using high fat diet (HFD)-induced obese experimental animal model. We also performed in silico studies to validate therapeutic effectiveness of hesperidin by performing protein-ligand docking and molecular dynamics simulation studies. Group 1 was identified as control group receiving vehicle only. Group 2 was marked as non-treated group receiving 60% HFD. While, other groups were treated daily with orlistat (120 mg/kg/d), hesperidin (55 mg/kg/d), combination of hesperidin (55 mg/kg/d) + orlistat (120 mg/kg/d). Hesperidin alone (P<0.001) and particularly in combination with orlistat (P<0.001), resulted in controlling the levels of HFD-altered biomarkers including random and fasting state of glycemia, leptin and insulin resistance. Similarly, hesperidin also improved the serum and tissue levels of leptin, interleukin-6 and tumor necrosis factor-alpha more significantly (P<0.05) when compared with that of orlistat. These results were found to be in accordance with the results of histopathological examination of pancreas, liver and adipose tissues. In-silico studies also proved that hesperidin binds to leptin receptor with higher affinity as compared to that of orlistat and induces the favorable variations in geometrical conformation of leptin receptor to promote its association with leptin which may lead to the cascades of reactions culminating the lipolysis of fats that may ultimately lead to cure obesity. The results of this study may be a significant expectation among the forthcoming treatment strategies for leptin and insulin resistance.
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Antiinflamatorios no Esteroideos/farmacología , Fármacos Antiobesidad/farmacología , Hesperidina/farmacología , Inflamación/tratamiento farmacológico , Resistencia a la Insulina , Obesidad/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/química , Fármacos Antiobesidad/química , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Quimioterapia Combinada , Hesperidina/química , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , Hiperlipidemias/patología , Inflamación/metabolismo , Inflamación/patología , Leptina/metabolismo , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Obesidad/metabolismo , Obesidad/patología , Orlistat/química , Orlistat/farmacología , Ratas WistarRESUMEN
Since the male secondary sex characters, libido and fertility are attributed to their major androgen hormone testosterone, the sub-optimum levels of testosterone in young adults may cause infertility and irregularities in their sexual behaviour. Such deficiency is often secondary to maladies involving testes, pituitary or hypothalamus that could be treated with an administration of exogenous testosterone. In the last few decades, the number of testosterone prescriptions has markedly increased to treat sub-optimal serum levels even though its administration in such conditions is not yet approved. On account of its associated cardiovascular hazards, the food and drug authority in the United States has issued safety alerts on testosterone replacement therapy (TRT). Owing to a great degree of conflict among their findings, the published clinical trials seem struggling in presenting a decisive opinion on the matter. Hence, the clinicians remain uncertain about the possible cardiovascular adversities while prescribing TRT in hypogonadal men. The uncertainty escalates even further while prescribing such therapy in older men with a previous history of cardiovascular ailments. In the current review, we analysed the pre-clinical and clinical studies to evaluate the physiological impact of testosterone on cardiovascular and related parameters. We have enlisted studies on the association of cardiovascular health and endogenous testosterone levels with a comprehensive analysis of epidemiological studies, clinical trials, and meta-analyses on the cardiovascular risk of TRT. The review is aimed to assist clinicians in making smart decisions regarding TRT in their patients.
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Enfermedades Cardiovasculares/inducido químicamente , Terapia de Reemplazo de Hormonas , Hipogonadismo/tratamiento farmacológico , Testosterona/efectos adversos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Animales , Enfermedades Cardiovasculares/epidemiología , Toma de Decisiones Clínicas , Terapia de Reemplazo de Hormonas/efectos adversos , Humanos , Hipogonadismo/sangre , Hipogonadismo/epidemiología , Masculino , Metaanálisis como Asunto , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Testosterona/deficiencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Calcitonin was discovered as a peptide hormone that was known to reduce the calcium levels in the systemic circulation. This hypocalcemic effect is produced due to multiple reasons such as inhibition of bone resorption or suppression of calcium release from the bone. Thus, calcitonin was said as a primary regulator of the bone resorption process. This is the reason why calcitonin has been used widely in clinics for the treatment of bone disorders such as osteoporosis, hypercalcemia, and Paget's disease. However, presently calcitonin usage is declined due to the development of efficacious formulations of new drugs. Calcitonin gene-related peptides and several other peptides such as intermedin, amylin, and adrenomedullin (ADM) are categorized in calcitonin family. These peptides are known for the structural similarity with calcitonin. Aside from having a similar structure, these peptides have few overlapping biological activities and signal transduction action through related receptors. However, several other activities are also present that are peptide specific. In vitro and in vivo studies documented the posttreatment effects of calcitonin peptides, i.e., positive effect on bone osteoblasts and their formation and negative effect on osteoclasts and their resorption. The recent research studies carried out on genetically modified mice showed the inhibition of osteoclast activity by amylin, while astonishingly calcitonin plays its role by suppressing osteoblast and bone turnover. This article describes the review of the bone, the activity of the calcitonin family of peptides, and the link between them.
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[This corrects the article DOI: 10.1371/journal.pone.0227637.].
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OBJECTIVE: The aim of the present study was to design an efficient delivery system with an anticipated swelling and drug release properties for a prolonged drug release as well as to target colon for various hydrophilic drugs. METHOD: For this purpose, the pH-responsive hydrogel comprising a combination of Eudragit and acrylic acid was formed. The hydrogels were characterized for spectral (FTIR), thermal (TGA/DSC), structural (XRD), and morphological (SEM) investigations. Oral tolerability was assessed in rabbits for biocompatibility and oral use of the prepared hydrogels. RESULTS: The results showed that an increased incorporation of Eudragit and cross-linking agent retorted the swelling, drug loading, and drug release properties at both acid (pH 1.2) and basic pH (pH 6.8 and 7.4) , while acrylic acid presented the inverse results. The oral tolerability and toxicity studies depicted that the developed hydrogels were safe up to 3800 mg/kg body weight and caused no hematological or histopathological changes when compared with the control group. CONCLUSION: Therefore, the newly developed formulations presented adequate swelling, drug loading, release behavior, and biocompatibility properties and thus can be used as a promising tool for the colonic delivery of various hydrophilic drugs.
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Materiales Biocompatibles/química , Colon/metabolismo , Sistemas de Liberación de Medicamentos , Hidrogeles/química , Losartán/metabolismo , Ácidos Polimetacrílicos/química , Acrilatos/administración & dosificación , Acrilatos/química , Administración Oral , Animales , Materiales Biocompatibles/síntesis química , Colon/química , Liberación de Fármacos , Hidrogeles/administración & dosificación , Hidrogeles/síntesis química , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Losartán/química , Ácidos Polimetacrílicos/administración & dosificación , Ácidos Polimetacrílicos/síntesis química , ConejosRESUMEN
This study describes the fabrication of chemically crosslinked pectin-based LA-co-MAA hydrogels through free radical polymerization technique for the colonic delivery of oxaliplatin. Methylene bisacrylamide was used as a crosslinking agent and ammonium persulfate as an initiator. The successful fabrication and drug loading were confirmed through Fourier transform infrared spectroscopy (FTIR). The thermal investigations through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) suggested the higher thermal stability of the unloaded and OXP-loaded formulations as compared to the raw materials. X-ray diffraction (XRD) analysis showed a decrease in crystallinity after crosslinking. The swelling, drug loading, and drug release were increased with an increase in the concentration of pectin and lactic acid (LA) while methacrylic acid (MAA) displayed an inverse behavior. The in-vitro biodegradability was evaluated against lysozyme and collagenase. The results showed that the hydrogels were stable against blank PBS as compared to lysozyme and collagenase. MTT-assay proved that the blank hydrogels were cytocompatible while free OXP and OXP-loaded hydrogels displayed dose-dependent effect against Vero, MCF-7, and HCT-116 cell lines. The oral tolerability study in rabbits confirmed that the hydrogel dispersion was well-tolerable up to 3650â¯mg/kg of body weight without causing any histopathological or hematological changes when compared with the control group.