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The present investigation was carried out for a comparative volatile study and aroma profiling of Hedychium flavescens. The headspace gas chromatography mass spectrometry (GC-MS) analysis of flowers (HS-F) and rhizome (HS-R); GC-MS analysis of flower essential oil (EO-F), flower absolute (AB-F) and rhizome essential oil (EO-R) revealed 27, 19, 19, 15 and 12 compounds which constitute 96.22%, 96.93% 97.43%, 86.79% and 97.62% composition, respectively. The identification results demonstrated that flowers and rhizome were rich in ß-pinene, 1,8-cineol, linalool and E-ß-caryohyllene components. ß-Pinene was the most abundant component in HS-R (38.99%), EO-R (26.61%); linalool in HF-F (25.34%) and EO-F (25.99%) and ρ-vinyl-guaiacol in AB-F (32.19%), respectively. The aroma profile of H. flavescens was dominated with floral and jasmine (flowers); spicy, earthy and herbal (EO-F); floral and balsamic (AB-F); herbal, pungent, spicy and earthy (rhizome and EO-R) notes. Based on aroma profile, AB-F was evaluated as potential ingredient for perfume industry.
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Dracocephalum heterophyllum Benth (Lamiaceae) is a wild herb that possesses a number of biologically active phytomolecules. The aim of this study was to investigate comparative essential oils (EOs) composition and biological (antimicrobial and anti-diabetic) activities of D. heterophyllum from higher altitudes. Gas chromatography-mass spectrometry (GC/MS) and gas chromatography-flame ionisation detector (GC-FID) were carried out for the identification and quantification of EOs components. The hydrodistillation of fresh aerial part of D. heterophyllum gave (0.1-0.8) % w/v EOs yield. Altogether, twenty-seven constituents were identified in the among samples representing (91.0-98.2) % of the EOs composition. The ß-citronellol (31.5-83.7) % contributes major constituent in all samples. The in vitro antimicrobial potential of EOs was examined against six human pathogenic bacterial and two phytopathogens fungal strains. Anti-diabetic activity exhibits excellent α-amylase and better α-glucosidase enzymes inhibitor properties.
Assuntos
Anti-Infecciosos , Lamiaceae , Óleos Voláteis , Humanos , Óleos Voláteis/química , Cromatografia Gasosa-Espectrometria de Massas , Hipoglicemiantes/farmacologia , Hipoglicemiantes/análise , Lamiaceae/química , Anti-Infecciosos/químicaRESUMO
The critical time window between the incidence of frostbite injury and the initiation of treatment in remote snowbound areas is a determining factor for an effective therapeutic response. It is an emergency condition and challenging to treat due to the poor vascularity of affected body parts, and it requires immediate action. In addition to cold trauma-induced tissue damage, the inflammatory mediators majorly contribute to pathologic aggravations. We have designed and evaluated a topical "nano-spray gel (NSG)" formulation, which is based on a combination of liposomal heparin sodium (Hp) and ibuprofen (Ibu) for rapid relief of frostbite injury in extremely low temperatures. The scientific literature suggests that heparin is associated with rapid endothelial cell repair, normalizing blood circulation in capillaries, and has a potential role in wound healing. Hp-containing liposomes were prepared by the extruder method, which suitably formulated an ibuprofen-containing gel to obtain a nano-Spray formulation (HLp-Ibu-NSG) applicable for topical delivery. A single spray puff of the formulation delivers â¼154 mg of the gel, which corresponds to â¼205 U of heparin. In this study, heparin liposomes exhibited significant healing of wound in vitro (scratch assay, fibroblast cells) and in vivo (wound healing in Sprague Dawley rats) at a low dose. In the rat model of frostbite injury, the HLp-Ibu-NSG formulation demonstrated significant reduction in the wound area (up to â¼96%) and improvement of histopathology in 14 days as compared to the control groups. No edema and erythema were detected post-treatment of HLp-Ibu-NSG in the affected area. The underlying mechanism was delineated as a modulation of the inflammatory cytokine (IL-6, TNF-α, IL-10, IL-4) mediators at the wound site and blood circulation to foster frostbite healing. Future clinical studies on the nano-spray gel are required to evaluate its efficacy for the treatment of frostbite symptoms. The instant on-site application of this formulation might be helpful in saving extremities of soldiers, mountaineers, and pilgrims having frostbite.
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Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive deterioration of cognitive functions. The pathological hallmarks are extracellular deposits of amyloid plaques and intracellular neurofibrillary tangles of tau protein. The cognitive deficits seen are thought to be due to synaptic dysfunction and neurochemical deficiencies. Various neurochemical abnormalities have been observed during progressive ageing, and are linked to cognitive abnormalities as seen with the sporadic form of AD. Acetylcholinesterase inhibitors are one of the major therapeutic strategies used for the treatment of AD. During the last decade, various new therapeutic strategies have shown beneficial effects in preclinical studies and under clinical development for the treatment of AD. The present review is aimed at discussing the neurobiology of AD and association of neurochemical abnormalities associated with cognitive deterioration and new therapeutic strategies for the treatment of AD.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Neurobiologia/tendências , Neurofarmacologia/tendências , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/administração & dosagem , Terapia de Reposição Hormonal/tendências , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Proteínas tau/antagonistas & inibidores , Proteínas tau/metabolismoRESUMO
Hypoxia induced oxidative stress and neurodegeneration in the hippocampus has been implicated for memory impairment in conditions like stroke, ischemia and hypobaric hypoxia. The present study, aimed at investigating the potential of ethanolic extract of Cicer microphyllum seeds (CSE) for amelioration of global hypoxia induced neurodegeneration in CA1 region of hippocampus. CSE supplementation considerably reduced neurodegeneration and dendritic atrophy in CA1 neurons along with improvement of memory in hypoxic rats. This effect of CSE was partly attributed to its antioxidant activity resulting in reduction of lipid peroxidation, protein oxidation and DNA damage during exposure to chronic hypoxia. CSE also promoted dendritic arborization through activation of estrogen receptor beta (ERß) and phosphorylation of extracellular signal regulated kinase (ERK1/2) which was independent of brain derived neurotrophic factor (BDNF) mediated signalling mechanisms. Extra nuclear activation of ERK1/2 by ERß resulted in phosphorylation of cyclic AMP response element binding protein (CREB) leading to increased expression of PSD-95.These molecular alterations translated to behavioural changes in CSE administered hypoxic animals that performed better in Morris Water Maze Task as compared to vehicle treated hypoxic animals. Toxicological studies show NOEAL > 2000 mg/kg b.w. for oral administration of CSE indicating its safety for consumption. Our findings not only suggest the neuroprotective potential of CSE in hypoxia but also provide evidence for involvement of estrogen receptor and pCREB mediated nootropic effect of the extract.
Assuntos
Cicer , Receptor beta de Estrogênio/metabolismo , Hipocampo/metabolismo , Hipóxia/metabolismo , Animais , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Memória/fisiologia , Transtornos da Memória/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Nootrópicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , SementesRESUMO
Stimulation as well as inhibition of GABAB (Gamma amino butyric acid) receptors has been reported to show beneficial effects in Alzheimer's disease (AD). Experimental evidences suggest that the use of GABAergic agents could influence learning and memory. The present study was designed to investigate the possible role of GABAB receptors in streptozotocin (STZ)-induced behavioral and biochemical abnormalities in rats. Herein STZ was infused (3mg/kg) bilaterally on alternate days (day 1 and day 3) to produce experimental dementia in rats. STZ-infused rats were then treated with baclofen (GABABR agonist) 5 and 10mg/kg i.p. and CGP35348 (GABABR antagonist) 25 and 50mg/kg i.p. one week following STZ infusion for 15days. Cognitive functions were assessed by using Morris water maze (MWM) and object recognition task (ORT). Levels of malondialdehyde (MDA.), reduced glutathione (GSH), andacetylcholinesterase (AChE) were determined to evaluate oxidative stress and cholinergic function. STZ-infused rats showed decreased memory retention, elevated levels of MDA, increased AChE activity, reduced GSH levels. The combination of STZ with increasing doses of Baclofen further induced a higher decrease in memory retention and increase in oxidative stress. CGP35348 restored cognitive functions and AChE activity in STZ-infused rats. The cognitive enhancement following CGP35348 may be due to its ability to restore cholinergic, serotonergic and dopaminergic function, and its antioxidant activity. Therefore, it would be safe to conclude that the pharmacological blockade of GABAB receptors would be therapeutic in the management of cognitive disorders such as Alzheimer's disease.
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Demência/tratamento farmacológico , Demência/metabolismo , Nootrópicos/farmacologia , Compostos Organofosforados/farmacologia , Receptores de GABA-B/metabolismo , Acetilcolinesterase/metabolismo , Animais , Baclofeno/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Cognição/fisiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Distribuição Aleatória , Ratos Wistar , Receptores de GABA-A/metabolismo , Reconhecimento Psicológico/efeitos dos fármacos , Reconhecimento Psicológico/fisiologia , EstreptozocinaRESUMO
Nymphaea x rubra Roxb. ex Andrews (N. rubra) has been widely reported for immunomodulatory properties and treatment of piles, bleeding nose and dysentery in traditional medicinal systems. However, its in-vitro and in-vivo toxicity studies have never been investigated. So, the present study was designed to investigate in-vitro and in-vivo toxicity of methanolic extract of N. rubra rhizome in rats. In-vitro cytotoxicity studies were conducted for different doses of extract in N2a cell lines. For in-vivo toxicity studies, SD rats were divided into three groups and administered with 0, 300 and 2000 mg/kg b. w., p. o., of N. rubra extract respectively. In acute toxicity studies, female animals after extract administration animals were sacrificed for hematological profiling and gross necropsy. In sub-acute toxicity studies, both male and female animals were administered with extract daily for 14 days and were sacrificed for hematological, biochemical and histological examination. Body weight and food water intake was measured daily and animals were observed for visual toxic effects, behavioral changes and mortality. During in-vivo toxicity studies, none of the animals showed signs of toxicity and mortality during toxicity studies. The present findings suggest its safety and NOAEL of N. rubra rhizome extract to be > 2000 mg/kg b. w.
Assuntos
Nymphaea/química , Extratos Vegetais/toxicidade , Rizoma/química , Animais , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Aguda , Testes de Toxicidade SubagudaRESUMO
OBJECTIVES: Reviewed the epidemiology, clinical characteristics, mechanisms, and treatment of tuberculosis associated chronic obstructive pulmonary disease. DATA SOURCE: We searched PubMed, EMBASE, and the CINAHL from inception to June 2016. We used the following search terms: Tuberculosis, COPD, Tuberculosis associated COPD, and so forth. All types of study were chosen. RESULTS AND CONCLUSION: Chronic obstructive pulmonary disease (COPD) and tuberculosis are significant public health problems, particularly in developing countries. Although, smoking is the conventional risk factor for COPD, nonsmoking related risk factors such as biomass fuel exposure, childhood lower-respiratory tract infections, chronic asthma, outdoor air pollution, and prior history of pulmonary tuberculosis have become important risk factors of COPD, particularly in developing countries. Past history of tuberculosis as a risk factor of chronic airflow obstruction has been reported in several studies. It may develop during the course of tuberculosis or after completion of tuberculosis treatment. Developing countries with large burden of tuberculosis can contribute significantly to the burden of chronic airflow obstruction. Prompt diagnosis and treatment of tuberculosis should be emphasized to lessen the future burden of chronic airflow obstruction.
Assuntos
Asma/complicações , Doença Pulmonar Obstrutiva Crônica/complicações , Infecções Respiratórias/complicações , Tuberculose Pulmonar/complicações , Tuberculose/complicações , Deficiência de Vitamina D/complicações , Idoso , Poluentes Atmosféricos/toxicidade , Asma/epidemiologia , Efeitos Psicossociais da Doença , Feminino , Combustíveis Fósseis/toxicidade , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Infecções Respiratórias/epidemiologia , Fatores de Risco , Fumar/epidemiologia , Fatores Socioeconômicos , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Deficiência de Vitamina D/epidemiologiaRESUMO
Both chronological aging and chronic hypoxia stress have been reported to cause degeneration of hippocampal CA3 neurons and spatial memory impairment through independent pathways. However, the possible occurrence of precocious biological aging on exposure to single episode of global hypoxia resulting in impairment of learning and memory remains to be established. The present study thus aimed at bridging this gap in existing literature on hypoxia induced biological aging. Male Sprague Dawley rats were exposed to simulated hypobaric hypoxia (25,000ft) for different durations and were compared with aged rats. Behavioral studies in Morris Water Maze showed decline in learning abilities of both chronologically aged as well as hypoxic rats as evident from increased latency and pathlength to reach target platform. These behavioral changes in rats exposed to global hypoxia were associated with deposition of lipofuscin and ultrastructural changes in the mitochondria of hippocampal neurons that serve as hallmarks of aging. A single episode of chronic hypobaric hypoxia exposure also resulted in the up-regulation of pro-aging protein, S100A9 and down regulation of Tau, SNAP25, APOE and Sod2 in the hippocampus similar to that in aged rats indicating hypoxia induced accelerated aging. The present study therefore provides evidence for role of biological aging of hippocampal neurons in hypoxia induced impairment of learning and memory.
Assuntos
Senilidade Prematura/etiologia , Envelhecimento/fisiologia , Comportamento Animal/fisiologia , Disfunção Cognitiva/etiologia , Hipocampo/metabolismo , Hipóxia/complicações , Aprendizagem em Labirinto/fisiologia , Memória Espacial/fisiologia , Envelhecimento/metabolismo , Senilidade Prematura/metabolismo , Senilidade Prematura/patologia , Senilidade Prematura/fisiopatologia , Animais , Disfunção Cognitiva/fisiopatologia , Hipocampo/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia arjuna (Roxb. ex DC.) Wight & Arn. (T. arjuna) has been widely used in the traditional ayurvedic system of medicine as a cardioprotectant and for acute and chronic renal diseases supporting its ethnopharmacological use. AIM OF THE STUDY: The present study aimed at evaluating the diuretic action of an alcoholic extract of T. arjuna and its possible use as a prophylactic to prevent vascular leakage during acute mountain sickness at high altitude. MATERIALS AND METHODS: Rats were exposed to hypobaric hypoxia simulated to an altitude of 27,000 ft. in a decompression chamber for 12h. T. arjuna bark extract was administered at a single dose of 150 mg/kg (p.o.) to male Sprague Dawley rats (200 ± 20 g) 30 min prior to exposure. Total urine volume was measured during exposure to hypobaric hypoxia. The animals were then investigated for cerebral vascular leakage and serum concentration of sodium, potassium, renin, angiotensin-II, aldosterone and atrial natriuretic peptide (ANP). RESULTS: T. arjuna ameliorated acute hypobaric hypoxia induced decrease in glomerular filtration rate (p<0.5), increased total urine output (p<0.5) and prevented cerebral vascular leakage in hypoxic rats. T. arjuna treated animals also showed decrease in serum levels of renin (p<0.001) and angiotensin-II (p<0.5) as compared to placebo treated animals. Administration of T. arjuna attenuated acute hypobaric hypoxia induced oxidative stress, improved aldosterone levels and altered electrolyte balance in animals through ANP dependent mechanism. CONCLUSION: Results of the present study indicate towards diuretic potential of hydro-alcoholic extract of T. arjuna bark and provide evidence for its novel application as a prophylactic to attenuate acute hypobaric hypoxia induced cerebral vascular leakage through ANP mediated modulation of renin-angiotensin-aldosterone system.
Assuntos
Diuréticos/farmacologia , Diuréticos/uso terapêutico , Hipóxia/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Terminalia , Aldosterona/sangue , Angiotensina II/sangue , Animais , Fator Natriurético Atrial/sangue , Proteínas Sanguíneas/análise , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Diuréticos/toxicidade , Taxa de Filtração Glomerular/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Hipóxia/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Fitoterapia , Casca de Planta , Extratos Vegetais/toxicidade , Potássio/sangue , Ratos Sprague-Dawley , Renina/sangue , Sódio/sangueRESUMO
Ischemic preconditioning (IPC) is well demonstrated to produce cardioprotection by phosphorylation and subsequent inactivation of glycogen synthase kinase-3ß (GSk-3ß) in the normal rat heart, but its effect is attenuated in the diabetic rat heart. This study was designed to investigate the effect of zinc chloride and zinc ionophore pyrithione (ZIP) on the attenuated cardioprotective potential of IPC in the diabetic rat heart. Diabetes mellitus (DM) was induced by a single intraperitoneal administration of streptozotocin (STZ) (50 mg/kg; i.p). The isolated perfused rat heart was subjected to 30 minutes of ischemia followed by 120 minutes of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and cardiac injury was measured by estimating lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in the coronary effluent. Also, GSK-3ß was measured and neutrophil accumulation was measured by estimating myeloperoxidase (MPO) levels. IPC significantly decreased the myocardial infarct size, the release of LDH and CK-MB, the GSK-3ß levels and the MPO levels in the normal rat heart. Pre- and post-ischemic treatment with zinc chloride and zinc ionophore pyrithione (ZIP) in the normal and diabetic rat hearts significantly decreased the myocardial infarct size, the level of CK-MB and LDH in the coronary effluent and GSK-3ß and MPO levels. Our results suggest that pharmacological preconditioning with zinc chloride and ZIP significantly restored the attenuated cardioprotective potential of IPC in the diabetic rat heart.
Assuntos
Cardiotônicos/farmacologia , Cloretos/farmacologia , Complicações do Diabetes , Diabetes Mellitus Experimental , Infarto do Miocárdio , Miocárdio/metabolismo , Piridinas/farmacologia , Tionas/farmacologia , Compostos de Zinco/farmacologia , Animais , Complicações do Diabetes/metabolismo , Complicações do Diabetes/patologia , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Feminino , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/prevenção & controle , Miocárdio/patologia , Ratos , Ratos WistarRESUMO
BACKGROUND: Epidural injections (EI) are the most commonly performed minimally invasive intervention to manage chronic low back pain (CLBP) with lumbosacral radicular pain (LRP). Local anesthetic (LA) and/or steroids are frequently used injectates for EI and are reported with variable effectiveness. The majority of earlier studies have used either caudal, transforaminal (TF), or undefined interlaminar approaches for EI. The parasaggital interlaminar (PIL) approach route is reported to have good ventral epidural spread and comparable effectiveness to the TF route. However, there is a lack of head-to-head comparative effectiveness research of LA with or without steroid for managing CLBP with LRP using a PIL approach. OBJECTIVE: To compare the effectiveness of EI of LA alone and LA with steroid using a PIL approach for managing CLBP with LRP. STUDY DESIGN: Randomized, double blind, active control one year follow-up study. SETTING: Interventional pain management clinic in a tertiary care center in India. METHODS: Sixty-nine patients were randomized to receive fluoroscopic guided EI of either 8 mL of 0.5% lidocaine (group L, n = 34) or 6 mL of 0.5% lidocaine mixed with 80 mg (2 mL) of methylprednisolone acetate (group LS, n = 35). Patients were evaluated for pain intensity using 0 - 10 numerical rating scale (NRS) and functional disability using Modified Oswestry Disability Questionnaire (MODQ) at baseline; and 2 weeks, one, 2, 3, 6, 9, and 12 months after injection. Patients with inefficacy with the initial injection or response deterioration received an additional injection of the same injectate and dose. Patients were evaluated for achieving effective pain relief (EPR, i.e., ≥ 50% from baseline), overall NRS and MODQ, number of injections, and presence of ventral and perineural spread over one year follow-up. Primary outcome was proportion of patients achieving EPR at 3 months. RESULTS: A significantly higher proportion of patients achieved EPR at 3 months in group LS [30 (86%, 90% CI 73% - 93%)] as compared to group L [17 (50%, 90% CI 36% - 64%)] (P = 0.02). Similar results were obtained at 6, 9, and 12 months, respectively. The probability of achieving EPR was significantly higher in group LS at various time-points during the one year follow-up as compared to group L (P = 0.01) A significant reduction in NRS and improvement in MODQ were observed at all time-points post-intervention compared to baseline (P < 0.001) in both groups. NRS and MODQ scores were significantly lower in group LS as compared to group L at all time intervals post baseline. On average patients in group L received 2.0 (0.85) and group LS received 1.7 (0.71) injections annually (P = 0.07). Ventral epidural spread was comparable in both groups (97%). No major complications were encountered in either group; however, intravascular spread of contrast was noted during 2 injections (one in each group) requiring relocation. LIMITATIONS: A single center study, lack of documentation of adjuvant therapies like individual analgesic medication, and lack of placebo group. CONCLUSIONS: Using a PIL approach and the addition of steroid to LA for EI may provide superior effectiveness in terms of extent and duration of pain relief for managing CLBP with unilateral LRP, even though, local anesthetic alone also was effective. TRIAL REGISTRATION: CTRI/2014/04/004572
Assuntos
Analgesia Epidural/métodos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Dor Lombar/tratamento farmacológico , Esteroides/administração & dosagem , Esteroides/uso terapêutico , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Método Duplo-Cego , Feminino , Fluoroscopia , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Lidocaína/administração & dosagem , Lidocaína/uso terapêutico , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/análogos & derivados , Metilprednisolona/uso terapêutico , Acetato de Metilprednisolona , Pessoa de Meia-Idade , Manejo da Dor , Medição da Dor , Resultado do TratamentoRESUMO
INTRODUCTION: Adrenal Myelolipoma is a rare benign neoplasm, which contains mature adipose tissue and variable amounts of haematopoietic elements. Most lesions are small and asymptomatic, discovered incidentally during autopsy or imaging studies performed for other reasons. CASE PRESENTATION: Here we reported a series of two cases of giant myelolipomas of the adrenal gland; first one the largest tumor reported so far presented with massive hemorrhage and the second case introduced with its rare unreported presentation of adrenal myelolipomas i.e. a large abscess. DISCUSSION: Adrenal myelolipoma is a rare and asymptomatic tumor usually discovered incidentally in less than 1% of population on autopsy or imaging performed for other reasons. There is an increasing incidence of large adrenal myelolipoma (> 10 cm) presenting with life threatening and recurrent retroperitoneal hemorrhage along with other complications as abscess. To avoid such a life-threatening situation, authors recommend close monitoring and consideration of urgent surgical intervention for tumors larger than 4 cm at presentation or increase in size or change in appearance during follow-up.
RESUMO
Movement disorders rank among the most common neurological disorders. During the last two decades substantial progress has been made in understanding of the pathological basis of these disorders. Although, several mechanisms have been proposed, downregulation of cyclic nucleotide mediated signaling cascade has consistently been shown to contribute to the striatal dysfunctioning as seen in movement disorders. Thus, counteracting dysregulated cyclic nucleotide signaling has been considered to be beneficial in movement disorders. Cyclic nucleotide phosphodiesterases (PDEs) are the enzymes responsible for the breakdown of cyclic nucleotides and upregulation in PDE activity has been reported in various movement disorders. Thus, PDE inhibition is considered to be a novel strategy to restore cerebral cyclic nucleotide levels and their downstream signalling cascade. Indeed, various PDE inhibitors have been tested pre-clinically and were reported to be neuroprotective in various neurodegenerative disorders associated with movement disabilities. In this review, we have discussed a putative role of PDE inhibitors in movement disorders and associated abnormalities.
Assuntos
Terapia de Alvo Molecular/métodos , Transtornos dos Movimentos/tratamento farmacológico , Nucleotídeos Cíclicos/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Transdução de Sinais , Animais , Humanos , Transtornos dos Movimentos/enzimologia , Transtornos dos Movimentos/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Glutamate and γ-aminobutyric acid (GABA) are the major excitatory and inhibitory neurotransmitter systems, respectively in the central nervous system (CNS). Dysregulation, in any of these or both, has been implicated in various CNS disorders. GABA acts via ionotropic (GABA(A) and GABA(C) receptor) and metabotropic (GABA(B)) receptor. Dysregulation of GABAergic signaling and alteration in GABA(B) receptor expression has been implicated in various CNS disorders. Clinically, baclofen-a GABA(B) receptor agonist is available for the treatment of spasticity, dystonia etc., associated with various neurological disorders. Moreover, GABAB receptor ligands has also been suggested to be beneficial in various neuropsychiatric and neurodegenerative disorders. The present review is aimed to discuss the role of GABA(B) receptors and the possible outcomes of GABA(B) receptor modulation in CNS disorders.
Assuntos
Ansiedade/terapia , Doenças do Sistema Nervoso Central/terapia , Depressão/terapia , Moduladores GABAérgicos/uso terapêutico , Receptores de GABA-B/metabolismo , Transtornos Relacionados ao Uso de Substâncias/terapia , Ácido gama-Aminobutírico/metabolismo , Ansiedade/metabolismo , Doenças do Sistema Nervoso Central/metabolismo , Depressão/metabolismo , Moduladores GABAérgicos/farmacologia , Humanos , Ligantes , Conformação Proteica , Receptores de GABA-B/química , Transtornos Relacionados ao Uso de Substâncias/metabolismoRESUMO
Phosphodiesterase inhibitors have been reported to be beneficial in cognitive and motor disorders. In the present study, we have investigated the effects of RO 20-1724 (PDE4 inhibitor) and sildenafil (PDE5 inhibitor) in 3-nitropropionic acid (3-NP) induced experimental Huntington's disease in rats. 3-Nitropropionic acid was administered for 14 days (10 mg/kg i.p.) 1h following 3-NP administration, the rats were treated with either vehicle, RO 20-1724 (0.25 and 0.5 mg/kg i.p.) or sildenafil (2 and 4 mg/kg i.p.) for 14 days. Cognitive functions were assessed by using Morris water maze whereas, motor functions were assessed by spontaneous locomotor activity, limb withdrawal and suspended wire test at different time points. Biochemically, markers of oxidative stress and cell damage, such as reduced glutathione, malondialdehyde, nitrite and lactate dehydrogenase levels were assessed terminally in the brain homogenate. Chronic administration of 3-NP produced significant decrease in body weight, showed marked abnormalities in cognitive and motor functions. Further, significant oxidative-nitrosative stress and cell damage was also observed. Chronic administration of RO 20-1724 and sildenafil in 3-NP treated rats significantly and dose dependently attenuated 3-NP induced behavioral and biochemical abnormalities in rats. Both these drugs were equally effective in attenuating 3-NP induced neurotoxicity. These results suggesting that the inhibition of PDE4 and PDE5 would be therapeutic in neurodegenerative disorders associated with cognitive and motor dysfunction.
Assuntos
4-(3-Butoxi-4-metoxibenzil)-2-imidazolidinona/farmacologia , Comportamento Animal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Nitrocompostos/toxicidade , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Piperazinas/farmacologia , Propionatos/toxicidade , Sulfonas/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Encéfalo/metabolismo , Glutationa/metabolismo , L-Lactato Desidrogenase/metabolismo , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Purinas/farmacologia , Ratos , Ratos Wistar , Citrato de Sildenafila , Succinato Desidrogenase/metabolismoRESUMO
Upregulation in calcineurin (CaN) signaling has been implicated in various neurodegenerative disorders. In the present study, we have investigated the effect of FK506--a CaN inhibitor--on streptozotocin (STZ)-induced experimental dementia of the Alzheimer's type in rats. STZ was administered intracerebroventricularly to induce a cognitive deficit and oxidative stress. Nonimmunosuppressive doses (0.5 and 1 mg/kg postoperatively) of FK506 (tacrolimus) were administered for 21 day in STZ-treated rats. Cognitive functions were assessed using the Morris water maze and passive avoidance tasks. Malondialdehyde and nitrite glutathione levels, as well as acetylcholinesterase activity, were determined to evaluate oxidative stress and cholinergic functions. Lactate dehydrogenase levels were estimated and histological analysis of the dentate gyrus and the CA1 region of the hippocampus was carried out to identify degenerative changes. STZ produced significant deterioration of cognitive functions, oxidative stress, and degenerative changes in the cortical and hippocampal brain regions. FK506 dose-dependently attenuated STZ-induced cognitive deficits, oxidative stress, and degenerative changes in the cortex and hippocampus. These results suggest a potential role of CaN signaling in degenerative processes, and that inhibition of CaN may be useful in the treatment of neurodegenerative disorders such as Alzheimer's disease.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores de Calcineurina/farmacologia , Demência/tratamento farmacológico , Tacrolimo/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Inibidores de Calcineurina/administração & dosagem , Cognição/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Injeções Intraventriculares , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Estreptozocina/toxicidade , Tacrolimo/administração & dosagemRESUMO
Ondansetron is a serotonin receptor antagonist used widely in the prophylaxis and treatment of postoperative nausea and vomiting (PONV) and vomiting associated with cancer chemotherapy. The common side effects of ondansetron are fever, malaise, diarrhoea, constipation, and allergic reactions. Extra-pyramidal reactions are rare and cardiovascular side effects are even rarer. Even though its clinical safety has been established in a large number of studies, its adverse effects have been reported and these include cardiovascular events like acute myocardial ischemia and arrhythmias in adults.([1]) Studies of its adverse effects in children are few. We report a rare adverse effect of ondansetron in a 14-year-old girl, presenting as ventricular tachycardia.