RESUMO
Ayurveda is based largely upon two classics - Charaka-Samhita, representing the school of medicine, and Sushruta-Samhita representing that of surgery. These two texts mark the historic switch in the Indian medical tradition, from faith-based therapeutics to its reason-based variant [1]. The Charaka-Samhita, which acquired its present form in circa 1st century CE, uses two remarkable terms to designate the distinctness of these approaches: daiva-vyapashraya (literally, dependence on the unobservable) and yukti-vyapashraya (dependence on reason) [2].
Assuntos
Astrologia , Humanos , Ayurveda/história , EstudantesRESUMO
As a curious undergraduate studying Ayurveda, the first concept that intrigued me was Sushruta's take on foetal sex determination. At the time of conception, if the man's semen is in excess, a male foetus results; if the woman's menstrual blood is in excess, a female foetus results; if semen and menstrual blood are in equal measure, an intersex is formed.
Assuntos
Ayurveda , Fatores Sexuais , Feminino , Humanos , MasculinoRESUMO
The Gazette of India: Extraordinary published "The National Commission for Indian System of Medicine Notification." on February 17, 2022 [1]. This official document of the Government of India is worrying as it institutionalises a world view that has been gradually turning the ancient science of Ayurveda into a pseudoscience.
RESUMO
Ayurveda is a valuable legacy bequeathed to us by ancient Indian sage-physicians. The present paper discusses the epistemology of this ancient science and the misconceptions surrounding it. Diligent research, both theoretical and experimental, in the twentieth century could have ensured the graduation of this proto-science into a full-fledged science. Instead, epistemological misconceptions and intellectual sloth have thwarted its refinement and progress. The paper appeals for an epistemological break that would facilitate an evidence-based appraisal of Ayurveda's theories and practices. Such an appraisal would help realise Ayurveda's full potential in serving India's healthcare needs, especially at the level of primary care.
Assuntos
Ayurveda , Médicos , HumanosRESUMO
The SARS-CoV-2 virus has spread worldwide to cause a full blown pandemic since 2020. To date, several promising synthetic therapeutics are repurposed and vaccines through different stages of clinical trials were approved and being administered, but still the efficacy of the drugs and vaccines are yet to be decoded. This article highlights the importance of traditional medicinal plants and the phytomolecules derived from them, which possess in vitro antiviral and anti-CoV properties and further explores their potential as inhibitors to molecular targets of SARS-CoV-2 that were evaluated by in silico approaches. Botanicals in traditional medicinal systems have been investigated for anti-SARS-CoV-2 activity through in silico and in vitro studies. However, information linking structure of phytomolecules to their antiviral activity is limited. Most phytomolecules with anti-CoV activity were studied for inhibition of the human ACE2 receptor through which the virus enters host cells, and non-structural proteins 3CLpro and PLpro. Although the proteases are ideal anti-CoV targets, information on plant-based inhibitors for the CoV structural proteins, e.g., spike, envelope, membrane, nucleocapsid required further investigations. In absence of scientific evaluations through in vitro and biocompatibility studies, plant-based antivirals fall short as treatment options. Plant-based anti-SARS-CoV-2 therapeutics can be promising alternatives to their synthetic counterparts as they are economical and bear fewer chances of toxicity, side effects, and viral resistance. Our review could provide a systematic overview of the potential phytomolecules which can be repurposed and subjected to further modes of experimental evaluation to qualify for use in treatment and prophylaxis of SARS-CoV-2 infections.
Assuntos
COVID-19 , Antivirais/farmacologia , Humanos , Pandemias , SARS-CoV-2RESUMO
Fetal and early childhood exposure to low levels of chemicals formed in foods during heating, especially acrylamide (ACR) is of increased concern due to developmental neurotoxicity. The neurodevelopment during perinatal period is critical and evidence suggests that the gut microbiota plays a major role in shaping brain development and behavior. Pregnant Wistar rats provided with oral supplements a combination of fructo- and xylo-oligosaccharides (FOS + XOS, 3 g/kg/day) from gestation day 0 (GD 0) to postnatal day 21 (PND 21) were exposed to ACR (100 ppm, GD 6 to PND 21) in drinking water. While ACR exposure caused a significant reduction in the maternal gestational/ lactational body weight, preweaning body weights and behavioral alterations among male offspring, combination supplement of FOS + XOS had no significant effect. However, significantly diminished antioxidant enzyme (SOD and CAT) activities in the maternal and offspring brain were restored among rats given FOS + XOS supplementation. The prebiotic supplementation normalized elevated nitric oxide levels in the cerebellum of the offspring born to ACR exposed rats. Furthermore, prebiotics restored the activity of acetylcholinesterase (AChE) and improved the levels of dopamine (DA) in the maternal cortex. The protective effect of prebiotic supplementation was also discernible in the mitochondrial fraction of maternal brain regions. These findings suggest that prebiotic supplementation during pregnancy may be useful in attenuating the perinatal toxic effects associated with neurotoxin exposure.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/terapia , Oligossacarídeos/administração & dosagem , Prebióticos/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal/terapia , Acetilcolinesterase/metabolismo , Acrilamida , Animais , Comportamento Animal , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dopamina/metabolismo , Feminino , Masculino , Troca Materno-Fetal , Óxido Nítrico/metabolismo , Gravidez , Ratos WistarRESUMO
INTRODUCTION: Oral microbiome impacts health and disease. T2DM and periodontitis are associated. Neem (Azadiracta indica) has antibacterial activity against oral microbiota. OBJECTIVES: To characterize oral microbiota (OMB) in saliva samples of T2DM patients by Next generation sequencing. To analyze MCP-1 levels among the T2DM patients before and after a month of neem stick usage as a toothbrush. MATERIALS AND METHODS: Blood and saliva samples were collected from adult T2DM patients before and after the neem stick usage. Metagenomic sequencing was performed on saliva samples targeting V6 region of 16s rRNA. Serum MCP-1 levels were determined using a quantitative sandwich Human MCP-1 standard ABTS development kit (Peprotech, USA). RESULTS: The profile of oral microbiota of T2DM patients (n=24) consists of Streptococcus (95.8%) counts ranging from 2644 to 27,214, Veillonella (72.2%, counts 25-19,709, Neisseria (87.5%) 453-33,445), Rothia (63.6%, 233-6734), Actinomycetes (25%, 161-3730), Fusobacterium (21%, 2252-21,334), and Pigmentiphaga (12.5% 3-16,644). Oral microbiota in healthy controls (n=10), consists of Streptococcus (26.1%), Veillonella (21.9%), Neisseria (16.9%), Haemophilus (10.7%), Actinomycetes (2.6%), Rothia (3.1%), Oribacterium (1.7%). Post neem samples showed drastic reduction in the load of bacteria which was statistically significant. The mean serum MCP-1 before the use of neem stick was 265.18±79.44 (range 141.6-980.5pg/ml) and dropped to 33.6±7.35 after a month of neem stick usage (P value>0.001). CONCLUSION: OMB of T2DM patients and healthy controls were similar, however bacterial loads were significantly higher in T2DM patients. Use of neem stick has a statistically significant reduction on bacterial loads and MCP-1 levels in T2DM patients.
Assuntos
Quimiocina CCL2/sangue , Diabetes Mellitus Tipo 2/microbiologia , Glicerídeos/uso terapêutico , Microbiota/efeitos dos fármacos , Boca/microbiologia , Terpenos/uso terapêutico , Adulto , Idoso , Diabetes Mellitus Tipo 2/sangue , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/metabolismo , Saliva/microbiologiaRESUMO
Alzheimer's disease (AD) is a complex, multifactorial disease in which different neuropathological mechanisms are likely involved, including those associated with pathological tau and Aß species as well as neuroinflammation. In this context, the development of single multitargeted therapeutics directed against two or more disease mechanisms could be advantageous. Starting from a series of 1,5-diarylimidazoles with microtubule (MT)-stabilizing activity and structural similarities with known NSAIDs, we conducted structure-activity relationship studies that led to the identification of multitargeted prototypes with activities as MT-stabilizing agents and/or inhibitors of the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) pathways. Several examples are brain-penetrant and exhibit balanced multitargeted in vitro activity in the low µM range. As brain-penetrant MT-stabilizing agents have proven effective against tau-mediated neurodegeneration in animal models, and because COX- and 5-LOX-derived eicosanoids are thought to contribute to Aß plaque deposition, these 1,5-diarylimidazoles provide tools to explore novel multitargeted strategies for AD and other neurodegenerative diseases.
Assuntos
Inibidores de Ciclo-Oxigenase/farmacologia , Imidazóis/farmacologia , Inibidores de Lipoxigenase/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Relação Estrutura-Atividade , Doença de Alzheimer/tratamento farmacológico , Animais , Araquidonato 5-Lipoxigenase/metabolismo , Técnicas de Química Sintética , Inibidores de Ciclo-Oxigenase/química , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Humanos , Imidazóis/química , Leucotrienos/biossíntese , Inibidores de Lipoxigenase/química , Masculino , Camundongos Endogâmicos , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Terapia de Alvo Molecular , Prostaglandinas/metabolismo , RatosRESUMO
BACKGROUND: Today, minimally invasive procedures are becoming more popular because of the fast recovery. Rhinoplasty is a common facial plastic surgery procedure that can be associated with significant postoperative morbidities, especially periorbital edema and ecchymosis. The aim of this review is to summarize the results of published literature that studied interventions that decrease postoperative edema and ecchymosis after rhinoplasty, and provide evidence-based strategies for surgeons to incorporate into practice. METHODS: A systematic review of the PubMed, Scopus, and EMBASE databases was performed to investigate interventions studied to decrease postoperative edema and ecchymosis after rhinoplasty. After inclusion and exclusion criteria were applied, articles were grouped into one of the following categories: corticosteroids, other medications and herbal supplements, interventions to decrease intraoperative bleeding, other postoperative interventions, and surgical techniques. RESULTS: A total of 50 articles were included for review. Fourteen articles studied corticosteroids exclusively, whereas another 10 articles reviewed other medications and herbal supplements. Nine articles evaluated methods to decrease intraoperative bleeding during rhinoplasty, and four articles studied postoperative interventions to decrease edema and ecchymosis. Thirteen articles studied various surgical techniques to decrease postoperative morbidities. CONCLUSIONS: There was a consensus within the literature that steroids, intraoperative hypotension, intraoperative cooling, and head elevation postoperatively decrease postoperative edema and ecchymosis, whereas nasal packing and periosteal elevation before osteotomy increased these postoperative morbidities. Studies of herbal supplements may be incorporated into practice with minimal risk to the patient. More studies must be performed before recommending an external or internal approach to lateral osteotomy.
Assuntos
Edema/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Rinoplastia , Corticosteroides/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Equimose/etiologia , Equimose/prevenção & controle , Edema/etiologia , Adesivo Tecidual de Fibrina/uso terapêutico , Humanos , Hipotensão/etiologia , Complicações Intraoperatórias/etiologia , Lidocaína/efeitos adversos , Lidocaína/uso terapêutico , Osteotomia , Fitoterapia , Preparações de Plantas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
This work investigates the correlations existing among soil organic carbon (C), nitrogen (N), phosphorous (P), potassium (K), and physicochemical properties like clay mineralogy, textural components, soil aggregation, and land use pattern. Seven different locations were chosen in the tropical rainforest climate region of Assam, India, for the work. The soil texture classifications were clay, sandy clay loam, and sandy loam with mixed clay mineralogy consisting of tectosilicates and phylosilicates. Two distinct compositions of total Fe/Al oxides≥11.5 and <10.8% were observed along with two distinct groups of water stable soil aggregates of mean weight diameter≈6.42 and ≤3.26 mm. The soil clay and sand had positive and negative contributions respectively to the soil organic carbon (SOC) protection, which was observed to be dependent on lesser sand content, higher silt+clay content, and the presence of higher percentages of total Fe/Al oxides. Soil clay mineralogy suggested that the mineral, chlorite, favored retention of higher SOC content in a particular site. Under similar climatic and mineralogical conditions, both natural and anthropogenic soil disturbances destabilized SOC protection through SOM mineralization and soil aggregate destabilization as indicated by SOC protective capacity studies. Urbanization resulting in soil compaction contributed to enhanced SOC level through increased contact between the occluded organic carbon and the soil mineralogical constituents.
Assuntos
Monitoramento Ambiental , Solo/química , Silicatos de Alumínio , Carbono/análise , Argila , Índia , Nitrogênio/análise , Fósforo/análiseRESUMO
We describe a rare case of necrotizing fasciitis of the ear in an otherwise generally healthy 39-year-old man. The ear is rarely involved in this often-fatal disease. The diagnosis was suspected on the basis of clinical examination and confirmed by computed tomography and pathology of a biopsy specimen, which revealed subcutaneous gas formation and dermal infiltration of inflammatory cells, respectively. The patient was promptly treated with surgical debridement, intravenous antibiotics, and hyperbaric oxygen. He recovered well and subsequently underwent otoplastic reconstruction with very satisfactory results. By documenting this case, we aim to heighten awareness of necrotizing fasciitis of the head and neck in an effort to improve survival rates.
Assuntos
Pavilhão Auricular/patologia , Otopatias/diagnóstico , Fasciite Necrosante/diagnóstico , Infecções Estafilocócicas/diagnóstico , Adulto , Antibacterianos/uso terapêutico , Pavilhão Auricular/cirurgia , Otopatias/terapia , Fasciite Necrosante/terapia , Humanos , Oxigenoterapia Hiperbárica , Masculino , Infecções Estafilocócicas/terapiaRESUMO
Proper wound care has broad applications for all clinicians. Much of the future direction for enhancing wound repair focuses on key cells and growth factors, which is why possessing a strong understanding of the basic physiology of wound healing is imperative. This article first provides a thorough review of the phases of wound healing followed by a discussion on the latest wound management strategies. Wound conditions and surgical techniques are important components for optimizing wound healing and preventing complications. Special consideration has been given to the unique settings of contaminated wounds, open wounds, or avulsed tissue.
Assuntos
Cicatriz/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Técnicas de Fechamento de Ferimentos , Cicatrização/fisiologia , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Bandagens , Toxinas Botulínicas Tipo A/uso terapêutico , Detergentes/uso terapêutico , Humanos , Oxigenoterapia Hiperbárica , Tratamento de Ferimentos com Pressão Negativa , Fármacos Neuromusculares/uso terapêutico , Fenômenos Fisiológicos da Nutrição , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Cicatrização/efeitos dos fármacos , Cicatrização/imunologiaRESUMO
In the present work, the leaves of Azadirachta indica (locally known as the Neem tree) in the form of a powder were investigated as a biosorbent of dyes taking aqueous Congo Red solution as a model system. The sorbent was made from mature Neem leaves and was investigated in a batch reactor under variable system parameters such as concentration of the aqueous dye solution, agitation time, adsorbent amount, pH, and temperature. An amount of 0.6 g of the Neem leaf powder (NLP) per litre could remove 52.0-99.0% of the dye from an aqueous solution of concentration 2.87 x 10(-2) mmol l(-1) with the agitation time increasing from 60 to 300 min. The interactions were tested with respect to both pseudo first-order and second-order reaction kinetics; the latter was found to be more suitable. Considerable intra-particle diffusion was found to occur simultaneously. The sorption process was in conformity with Langmuir and Freundlich isotherms yielding values of the adsorption coefficients in the following ranges: Freundlich n: 0.12-0.19, Kf: 0.1039-0.2648 L g(-1); Langmuir qm: 41.24-128.26 g kg(-1), b: 443.3-1898.0 l mmol(-1), which supported favourable adsorption. The Langmuir monolayer capacity (qm) was high and the values of the coefficient b indicated the equilibrium, dye + NLP = dye...NLP being shifted overwhelmingly towards adsorption. Thermodynamically, the sorption process was exothermic with an average heat of adsorption of -12.75 kJ mol(-1). The spontaneity of the sorption process was also confirmed by the favourable values of Gibbs energy (mean values: -1.09 to -1.81 kJ mol(-1)) and entropy of adsorption (range: -18.97 to -56.32 J mol(-1)K(-1)). The results point to the effectiveness of the Neem leaf powder as a biosorbent for removing dyes like Congo Red from water.
Assuntos
Azadirachta/química , Corantes/química , Corantes/isolamento & purificação , Vermelho Congo/química , Vermelho Congo/isolamento & purificação , Purificação da Água/métodos , Adsorção , Biodegradação Ambiental , Cinética , Extratos Vegetais , Folhas de Planta , PósRESUMO
Two arbuscular mycorrhizal (AM) fungi Glomus macrocarpum and Glomus fasciculatum significantly improved growth and essential oil concentration of Foeniculum vulgare Mill. However, AM inoculation of plants along with phosphorus fertilization significantly enhanced growth, P-uptake and essential oil content of plants compared to either of the components applied separately. Among the two fungal inoculants, G. fasciculatum registered the highest growth at both levels of phosphorus used with up to 78% increase in essential oil concentration of fennel seeds over non-mycorrhizal control. The essential oil characterization by gas liquid chromatography revealed that the level of anethol was significantly enhanced on mycorrhization.
Assuntos
Foeniculum/crescimento & desenvolvimento , Foeniculum/microbiologia , Fungos/crescimento & desenvolvimento , Agricultura/métodos , Derivados de Alilbenzenos , Análise de Variância , Anisóis/análise , Cromatografia Gasosa , Cromatografia Líquida , Gorduras Insaturadas na Dieta/análise , Fertilizantes , FósforoRESUMO
In this study we evaluate the antifibrotic properties of PG-490-88, a water-soluble derivative of triptolide. Triptolide is an oxygenated diterpene that is derived from a traditional Chinese herb that has potent immunosuppressive and antitumor activity. We used the intratracheal bleomycin mouse model and found that PG490-88 inhibits fibrosis in the bleomycin group when given the same day or 5 days after bleomycin. PG490-88 also markedly reduced the number of myofibroblasts in the bleomycin treatment group. An enzyme-linked immunosorbent assay of transforming growth factor (TGF)-beta in the bronchoalveolar lavage fluid showed a significant decrease in TGF-beta in the PG490-88-treated groups compared to the bleomycin-treated group. Additionally, triptolide blocked bleomycin-induced increase in TGF-beta mRNA in cultured normal human lung fibroblasts. The efficacy of PG490-88 when administered late after bleomycin installation suggests a potential role in the treatment of idiopathic pulmonary fibrosis.
Assuntos
Bleomicina , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/uso terapêutico , Imunossupressores/uso terapêutico , Fenantrenos , Fibrose Pulmonar/tratamento farmacológico , Animais , Líquido da Lavagem Broncoalveolar/química , Sobrevivência Celular , Diterpenos/química , Medicamentos de Ervas Chinesas/química , Compostos de Epóxi , Fibroblastos/citologia , Fibroblastos/metabolismo , Imunossupressores/química , Inflamação/patologia , Pulmão/citologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Transcrição Gênica/efeitos dos fármacos , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
In this article, an integrated in vivo genotoxicity testing philosophy and a practical approach, as applied to pharmaceuticals, are described. Recently, there has been an effort to integrate the rodent (primarily rat) micronucleus assay with routine 2-4-week toxicokinetic studies. This approach has several advantages: 1) it utilizes the general principles of toxicology that govern the overall toxicity profile of a test substance; 2) factors such as the dose and/or route of drug administration, drug metabolism, principles of toxicokinetics, and saturation of defense mechanisms are considered in evaluating genotoxicity; 3) it uses the concept of administering multiple tolerable doses aiding in achieving steady state plasma drug levels, which is more relevant for risk assessment compared to high acute doses; and 4) it helps minimize the amount of drug, number of animals used, and other resources. This integration approach can be extended to other toxicology studies and other relevant genotoxicity endpoints may be assessed. Based on the experience in our laboratory, integrating micronucleus assessment in routine toxicology testing is promising and should be utilized when practical.
Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Testes de Mutagenicidade , Toxicologia/métodos , Direitos dos Animais , Animais , Dano ao DNA , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/economia , Indústria Farmacêutica , Humanos , Camundongos , Testes para Micronúcleos , Testes de Mutagenicidade/economia , Farmacocinética , Ratos , Toxicologia/economiaRESUMO
The objective of this study was to seek improvement in the emulsification efficacy of lecithin by formulation design. A Base Emulsion was developed containing lecithin as the primary emulsifier. The lecithin concentration and method of preparation of the Base Emulsion were optimized to obtain minimum particle size and creaming of the emulsion. Selected hydrophilic and hydrophobic synthetic surfactants were evaluated as secondary emulsifiers for their ability to reduce particle size of the Base Emulsion. The selection of type and concentration of the secondary emulsifier was done by application of the HLB method. The hydrophilic emulsifiers selected were Tween 80, Tween 20, Pluronic F68, and Pluronic F127. The hydrophobic surfactants studied included Span 20, Span 80, Pluronic P103, and Pluronic P123. The median droplet size of the Base Emulsion was 2.7 microns. Addition of the hydrophilic emulsifiers caused an increase in particle size and substantial creaming of the emulsions. Addition of three of four hydrophobic surfactants resulted in particle size reduction, but the emulsions showed substantial creaming. Span 20 was found to be the most effective secondary emulsifier. The median particle size of the emulsion was 1.7 microns. These results suggest that supplementing the hydrophilic attributes of lecithin with an appropriate type and amount of hydrophobic surfactant improves the emulsion properties by applying principles of formulation design.
Assuntos
Fosfatidilcolinas/administração & dosagem , Tensoativos/administração & dosagem , Química Farmacêutica , EmulsõesRESUMO
This multicenter, randomized, controlled clinical trial assessed the influence of sodium chloride intake on the antihypertensive effect of the calcium channel blocker isradipine. Participants with uncomplicated hypertension controlled by isradipine entered a 4-week sodium-restricted (60 to 80 mmol/24 h) period. Participants with urinary sodium levels < 120 mmol/24 h (n = 99) were randomized to placebo or sodium chloride (100 mmol/24 h) for 4 weeks, and then crossed over to the alternative treatment for an additional 4 weeks. Mean baseline systolic blood pressure was 151.9 +/- 16.7 mm Hg (mean +/- SD). During open-label isradipine treatment, systolic blood pressures for ad libitum sodium chloride and restriction were 134.1 +/- 11.1 and 132.1 +/- 12.2 mm Hg respectively; for double-blind sodium chloride restriction and supplementation: 133.6 +/- 12.6 and 138.5 +/- 12.8 mm Hg (P < .01). Urinary sodium excretion values for open-label isradipine ad libitum versus restricted were 140.6 +/- 61.9 versus 76.9 +/- 32.4 mmol/24 h; for double-blind restricted versus supplemented, sodium excretion was 120.5 +/- 68.9 v 175.9 +/- 68.7 mmol/24 h (P < or = .0001). Changes in urinary sodium excretion were not predictive of variations in blood pressure. Urinary sodium excretion during sodium restriction correlated directly with HDL-cholesterol (P < .02) and inversely with total cholesterol:HDL-cholesterol (P = .02), despite decreased total and saturated fat intake (P < .01). Sodium restriction was associated with significant reductions (P < .01) in virtually all macronutrients and electrolytes, and thus had an adverse impact on overall nutrition. The antihypertensive action of isradipine was not enhanced by dietary sodium chloride restriction, and the lipoprotein profile was least favorable with sodium chloride restriction.
Assuntos
Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Hipertensão , Isradipino/administração & dosagem , Cloreto de Sódio na Dieta/administração & dosagem , Adulto , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
1. The expression of neuronal isoform of nitric oxide synthase (nNOS) was studied in human retinal tissues. The cDNA sequence was cloned in human retinal poly (A)+ RNA by the RT-PCR method and encompassed an open-reading frame of 4,302 bp encoding 1,434 amino acids. This sequence showed a possibility of genetic polymorphism in comparison to human brain form. 2. Restriction fragment length polymorphism (RFLP) patterns of a partial cDNA fragment suggest that there is genetic polymorphism in the neuronal form of NOS. Important differences were observed in a certain region between human retinal and brain froms. This region is a result of frame shift by the addition of three cytidines. In this study, regions from human brain (cerebellum) and skeletal muscle as well as retina were sequenced to confirm the difference in this region. The sequences from these tissues were completely identical. This indicated that genetic polymorphism of nNOS gene was due to single base substitution and not frame shift phenomenon by addition or deletion of bases. 3. The nNOS mRNA of approximately 12 kb was detected by northern blot analysis. The lower level of the expression was distinguished in comparison to those of human brain and skeletal muscle. The cDNA transiently transfected into CHO-K1 cells expressed a protein which contained a significant level of NOS activity. The size of the nNOS was found to be approximately 160 kDa by both in vitro and in vivo translation systems. This NOS was calcium dependent and the K(m) for arginine was 4.4 microM. 4. The Ca+2, L-arginine and NADPH dependency along with the inhibitory effect of N-nitro-L-arginine on NOS activity were evaluated. The finding of a constitutive from of NOS in human retina, which is calcium-NADPH dependent, gives further credence to the possible role of nitric oxide in retinal function and neuronal diseases.
Assuntos
Proteínas do Olho/biossíntese , Isoenzimas/biossíntese , Óxido Nítrico Sintase/biossíntese , Retina/enzimologia , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Animais , Sequência de Bases , Células CHO , Cerebelo/enzimologia , Cricetinae , Cricetulus , DNA Complementar/genética , Proteínas do Olho/genética , Feminino , Humanos , Isoenzimas/genética , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Músculo Esquelético/enzimologia , Óxido Nítrico Sintase/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , RNA Mensageiro/genética , Proteínas Recombinantes de Fusão/biossíntese , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , TransfecçãoRESUMO
Epidemiologic studies from divergent geographic locations consistently demonstrate an inverse correlation between potassium intake and the prevalence of hypertension. Studies in experimental animals showed a varied blood pressure response to alterations in potassium intake. Spontaneously hypertensive rats and rats with renovascular hypertension manifest a hypotensive response to both potassium depletion and potassium supplementation. In contrast, potassium depletion induced by chronic mineralocorticoid administration is associated with an increase in blood pressure. Potassium supplementation in hypertensive subjects lowers blood pressure. Amelioration of diuretic-induced hypokalemia with potassium supplementation enhances the hypotensive effect of diuretics. Potassium depletion induced by dietary potassium restriction elevates blood pressure in normotensive and hypertensive subjects maintained on a normal sodium intake. Potassium depletion in humans is accompanied by sodium retention and calcium depletion. The hypertensive response to potassium depletion and the hypotensive response to potassium supplementation do not manifest if sodium intake is kept low. Sodium retention, altered response to vasoactive hormones, direct vasoconstrictive effects of hypokalemia, and calcium depletion may all contribute to blood pressure elevation during potassium depletion.