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1.
JNMA J Nepal Med Assoc ; 61(266): 819-821, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38289771

RESUMO

Klippel-Feil syndrome is a rare congenital bone disorder characterised by a triad of short neck, low posterior hairline and limited lateral bending of the neck with an annual incidence of 1 in 40,000 live births. It has remained an obscure term in the medical literature because of its variability in presentation and wide spectrum of anomalies involving multiple organ systems. It is unusual to find a case that has all three classical triad features. Here, we present a case of a 9-month-old infant who manifests not only all three classical triad features associated with Klippel-Feil syndrome but also demonstrates the presence of congenital heart disease, scoliosis, and renal ectopia. An early comprehensive evaluation of a suspected case is essential for diagnosis and counselling which impacts its prognosis, helps minimize social stigma and affords parents the opportunity to consider cosmetic surgery as an option, should they choose to pursue it. Keywords: case reports; congenital; heart diseases; Klippel-Feil syndrome; scoliosis.


Assuntos
Cardiopatias Congênitas , Síndrome de Klippel-Feil , Escoliose , Lactente , Humanos , Síndrome de Klippel-Feil/complicações , Síndrome de Klippel-Feil/diagnóstico , Escoliose/complicações , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Osso e Ossos , Rim/anormalidades , Doenças Raras/complicações
2.
J Environ Manage ; 309: 114691, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35168134

RESUMO

Groundwater irrigation has evolved the monocropping cultivation pattern to multi-cropping, especially in many arid/semi-arid tracts globally. Irrigation practices with the groundwater of poor quality can limit the selection of the crop, reduce crop yields and degrade the soil quality. The present study has been undertaken to identify the hydrogeochemical phenomena of groundwater systems in the south-western Birbhum district, India and to analyze groundwater suitability for irrigation during the pre-and post-monsoon cycles by adopting the Irrigation Water Quality Index (IWQI) using Multivariate Factor Analysis along with some traditional methods viz. sodium adsorption ratio, sodium percentage, magnesium hazards, residual sodium bicarbonate (RSBC) and carbonate (RSC), Wilcox's and USSL diagrams, permeability index and Kelly's index. The hydrogeochemical analysis revealed that chemical weathering and evaporation are predominant in the aquifer systems. Groundwater quality reflected soil salinity, sodicity and magnesium hazards risks and water toxicity to the sensitive plants at 0-46.4% of the post-monsoon samples and 0-38.4% of the pre-monsoon samples based on the individual traditional methods whereas about 97.73-98.88% of the total area was classified as moderate to severely unsuitable for irrigation during both seasons when integrated multiple parameters using the IWQI method. Prolonged use of such groundwater for irrigation is susceptible to causing moderate to severe infiltration problems at a greater extent of the study area. The study recommends adaptation of salinity, sodicity and RSC/RSBC reduction procedures (e.g., the use of acid and gypsum amendments in the irrigation lands and through water blending) and advanced irrigation practices (viz. drips, sprinklers and micro irrigations) to prevent soil degradation and increase crops productivity. Adopting Managed Aquifer Recharge procedures as well as rainwater harvesting in the areas bearing unsuitable water quality can dilute the ionic concentrations of the groundwater facies which in turn will improve the groundwater quality for irrigation.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Monitoramento Ambiental , Sistemas de Informação Geográfica , Índia , Poluentes Químicos da Água/análise , Qualidade da Água , Abastecimento de Água
3.
Environ Res ; 203: 111697, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34358509

RESUMO

This study appraised the groundwater fluoride (F-) endemicity and the exposure levels under the Central Tendency Exposure (CTE) condition and the Reasonable Maximum Exposure (RME) condition on the residents of the semi-arid parts of the Birbhum district of Peninsular India using a Variance Decomposition (Sobol Sensitivity Indices) approach combined with Monte Carlo Simulations. The study finds the national scale drinking water standard limit for F- (1.5 mg L-1) is inappropriate for the present survey area where F- concentration in groundwater varied between 0.26 and 11.82 mg L-1 and ~54.5% of the samples (N = 400) exceeded this limit. Therefore, estimated the optimum F- concentration of 0.733 mg L-1 for the region using the method recommended by the World Health Organization (WHO) to calculate the optimum F- limit at a regional scale. The average value of F- concentrations for this region (1.71 mg L-1) is considerably higher than the estimated optimum concentration or even the maximum permissible limits recommended for the subtropical regions (0.5-0.7 mg L-1). The exposure analysis revealed the infants and children as potentially vulnerable populations compared to adolescents and adults of the study area for CTE and RME scenarios. The multi-exposure pathways indicated oral intake as the main exposure pathway whereas exposure through dermal contact was insignificant for the residents of all age groups of this region. Based on the first, second and total order Sobol Sensitivity Indices, F- concentration (C) in groundwater, the groundwater ingestion rate and their combined interaction are the greatest significant parameters for the oral exposure model whereas C and its interaction effects with the proportion of the skin surface area in contact with groundwater as the utmost sensitive variables for the dermal health risks assessment model. The present study insists the inhabitants to intake defluoridated groundwater.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Adolescente , Adulto , Criança , Monitoramento Ambiental , Fluoretos/análise , Humanos , Índia/epidemiologia , Lactente , Método de Monte Carlo , Medição de Risco , Poluentes Químicos da Água/análise
4.
Sci Total Environ ; 805: 150323, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34818806

RESUMO

Access to clean drinking water has been acknowledged as a human right and assessing the hydrogeochemistry and groundwater quality status plays an important role in proving cleaner and safer water for human consumption. This study evaluated the sources and driving factors of the groundwater facies in the five major river basins (viz. Ajay, Mayurakshi, Kopai, Brahmani and Dwarka) of an agroeconomic semi-arid Indian tract through hydrogeochemical and principal component analyses based on 2200 groundwater samples (Ns = 2200) obtained during the pre- and post-monsoon cycles from 1100 wells (Nw = 1100). The results revealed that minerals weathering, ion/reverse ion exchange, mixing and evaporation processes along with anthropogenic inputs are responsible for the deteriorated groundwater quality of the river basins. The study has considered the cokriging approach that uses geostatistical and multivariate statistical techniques to interpolate a dataset. To determine the spatio-seasonal variabilities of the groundwater facies more accurately, the estimation accuracies of different interpolation techniques viz. inverse distance weighting, kriging/cokriging and splines techniques were compared and kriging/cokriging was found to represent the variability more accurately. Shannon's entropy theory was employed to assess the groundwater quality of the river basins as it eliminates the subjective bias and inherent uncertainties of the groundwater systems. Groundwater in ~37.45-38.42% of the total area was moderate to extremely poor for human consumption where 10.40-12.14%, 9.09-12.40%, 21.18-22.35%, 15.20-19.93% and 6.48-8.80% samples from the Ajay (Nw = 175), Brahmani (Nw = 175), Dwarka (Nw = 180), Kopai (Nw = 350) and Mayurakshi (Nw = 220) river basins exhibited unfit to drink water quality. The sensitivity of the water quality model was analyzed to identify the influences of the individual parameters which revealed that the outcome does not depend solely on one parameter. The study recommends adaptation of the treatment techniques to ensure clean drinking water for the residents. Managed aquifer recharge techniques might also improve the groundwater quality in certain areas.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Monitoramento Ambiental , Humanos , Índia , Rios , Poluentes Químicos da Água/análise , Qualidade da Água
5.
Sci Total Environ ; 787: 147657, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34000554

RESUMO

Prevalence of nitrate in different aquifer systems is a growing environmental and public health concern. Efforts were made for the first-time to achieve a higher accuracy in health risks characterization associated with the nitrate in groundwater of the diverse aquifer systems on the residents of a semi-arid rural tract of Lower Ganga Basin using Monte Carlo Simulations and Sobol Sensitivity analyses. The nitrate levels in groundwater varied between 0 and 508.3 mg/L with a mean of 19.79 ± 32.78 mg/L and 0-435.0 mg/L with a mean of 24.44 ± 35.15 mg/L during the pre-monsoon and post-monsoon periods, respectively. About 847.12-1000.25 km2 area of the survey area (total area 4545 km2) exhibited nitrate concentrations (C) > the pre-intervention limits (45-50 mg/L). Minor populations, especially the infants from the granite gneiss, Rajmahal traps, laterite, recent alluvial and old alluvial aquifer zones under the Central Tendency Exposure (CTE) condition and all the aquifer zones (including the Gondwana supergroup aquifer zone) under Reasonable Maximum Exposure (RME) scenarios, were characterized as being at high risks of methemoglobinemia, primarily due to ingestion of untreated nitrate contaminated groundwater. Residents of the alluvial aquifer zones of the study area were found to the most vulnerable to the groundwater nitrate toxicity through oral and dermal exposures. The study validated the prediction accuracies of different interpolation methods including the Spline, Kriging, polynomial and Inverse Distance Weighted and revealed that Kriging predicted the Spatio-seasonal variations of groundwater nitrate of the district more accurately. Sobol Sensitivity analysis revealed C and the interaction effects of C and groundwater Ingestion Rate (IR), and C and Fraction of skin area contacted with groundwater (F) as the influential parameters for oral and dermal health risks exposure models. Therefore, the study recommends to residents of the study area to consume treated groundwater to mitigate nitrate related health morbidities.

6.
Cureus ; 13(2): e13250, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33717757

RESUMO

The inherited disease of unilateral anotia and ipsilateral Bell's palsy is exceedingly uncommon, but it has a few other clinical manifestations. The prevalence of anotia in combination with congenital Bell's palsy is well-known by Berry-Treacher Collins and Goldenhar syndrome. Despite the prevalence of anotia in combination with Bell's palsy, there have been relatively very few case reports about the corresponding conditions in India. The aim of the paper is to discuss the anesthesia plan for a seven-year-old boy who underwent surgery for tongue-tie release.

7.
J Family Med Prim Care ; 10(11): 4290-4292, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35136804

RESUMO

Anaesthetic management of cardiac disorders in pregnancy has always been complicated and challenging. A rare but extremely fatal entity, peripartum cardiomyopathy (PPCM) is a life-threatening disease affecting the parturient with mortality rates as high as 35-50%. Developing in late pregnancy or immediately after delivery, this unique disorder endangers not only the mother but the baby as well. We report here a case of a 28-year-old female parturient presenting at 37 weeks of gestation for caesarean delivery with recently diagnosed peripartum cardiomyopathy (ejection fraction of 28%) complicated by severe preeclampsia. She developed cardiac failure just before the induction of anaesthesia. She was successfully resuscitated, operated under general anaesthesia and shifted to the critical care unit for further management.

8.
Sci Total Environ ; 705: 135801, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31838424

RESUMO

The present study evaluated the heavy metal contamination in groundwater and associated ecological and human health risks of a geologically and anthropogenically diverse semi-arid region of Birbhum district, India. For a reliable evaluation, concentrations of nine heavy metals in 680 groundwater samples (N = 680) which were collected during premonsoon and postmonsoon seasons of consecutive two years from 170 wells were measured. The human health risk assessment using the USEPA model which is based on single value for each parameter may inherit certain inaccuracy and uncertainties in the evaluation. Unlike earlier studies, a higher degree of accuracy in carcinogenic and noncarcinogenic health risk assessments was achieved through Monte Carlo simulations, sensitivity analysis and uncertainty analysis. The study revealed the occurrence of the target heavy metals in groundwater with mean dominance order of Fe > Zn > Sr > Mn > Cr > Pb > Ni > Cu > Cd where mean concentrations of the carcinogens, Pb and Fe exceeded their maximum permissible limits. The water quality status evaluated using the modified heavy metal pollution index, Nemerow index and Heavy metal evaluation index methods resulted in medium to high heavy metal contamination in groundwater within a large portion of the study area which indicated its unsuitability for drinking purpose. The study suspects a moderate to very high risk for the groundwater dependent ecosystems in major part of the study area. The study further revealed cancer risks, ranging from high to very high within the residents due to accumulative exposure of the carcinogenic heavy metals in groundwater through ingestion and dermal contact. Minor populations of the study area were found to be more vulnerable to the carcinogenic and noncarcinogenic diseases than teenagers and adults, mainly through oral exposure. The study recommends the residents to consume treated groundwater since the primary route of heavy metal exposure was identified to be the ingestion route.


Assuntos
Ecossistema , Água Subterrânea , Monitoramento Ambiental , Índia , Metais Pesados , Medição de Risco
9.
Cent Nerv Syst Agents Med Chem ; 19(3): 197-205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749420

RESUMO

BACKGROUND: In the present study, 4, 5-disubstituted triazol-3-thione derivatives were synthesized and evaluated for anticonvulsant activity along with neurotoxicity determination. MATERIALS AND METHODS: The synthesized compounds were characterized using FTIR, 1H-NMR and MS. The anticonvulsant activity was assessed by Maximal Electroshock (MES) test and subcutaneous Pentylenetetrazole (scPTZ) tests and neurotoxicity was assessed by rotarod test. Docking was also performed to study the interactions of compounds with LYS329 residue of gamma amino butyric acid aminotransferase (GABA-AT) using Autodock 4.2 software. RESULTS: The compounds 7a and 9a with significant pharmacological activity were also found to interact with LYS329 residue of GABA-AT by H-bond with a docking score of -5.92 kcal/mol (Ki = 41.99 µM) and -5.87 kcal/mol (Ki = 49.83 µM) respectively. CONCLUSION: Most of the compounds were found to be active in MES test but only seven showed protection in scPTZ test.


Assuntos
Anticonvulsivantes/síntese química , Desenho de Fármacos , Tionas/síntese química , Triazóis/síntese química , Animais , Anticonvulsivantes/uso terapêutico , Masculino , Camundongos , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Tionas/uso terapêutico , Triazóis/uso terapêutico
10.
Chemosphere ; 233: 164-173, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31173954

RESUMO

Human health risks associated with groundwater fluoride have been assessed using USEPA method in few parts of India, but those assessments were conducted based on a single value for each parameter, which may lead to certain inaccuracy and uncertainties in results. In this study, a higher degree of accuracy in health risk assessment was achieved through Monte Carlo simulations, sensitivity analysis and uncertainty analysis. As fluoride hazards to human health are chronic, a total of 4560 water samples (N = 4560) were collected during consecutive four seasons (2 pre-monsoon and 2 post-monsoon seasons; 1140 samples/season) from the entire Birbhum district, covering all the blocks and geological settings to obtain the spatiotemporal variation of fluoride level. The Empirical Bayesian Kriging geostatistical model was employed to determine fluoride endemic areas. Amongst all blocks, Nalhati-1 had exhibited the highest fluoride level (18.25 mg/L). The study revealed that most of the blocks are vulnerable to groundwater fluoride due to its occurrences in excess level. The average and 95th percentile values of total hazard index indicate that the infants and children populations of the district are more susceptible than the adults and teens. The sensitivity analysis revealed that water ingestion rate and fluoride concentration are the most influential parameters for higher risk of fluoride-related health hazards. Health risks were evaluated through ingestion and dermal exposure routes for infants, children, teens, and adult residents. The exposure was much higher through ingestion than dermal contacts. Ingestion of defluoridated water will reduce the health risks associated with groundwater fluoride exposure.


Assuntos
Fluoretos/toxicidade , Água Subterrânea/análise , Poluentes Químicos da Água/toxicidade , Adolescente , Adulto , Teorema de Bayes , Criança , Pré-Escolar , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Fluoretos/análise , Humanos , Índia , Lactente , Método de Monte Carlo , Medição de Risco , Estações do Ano , Incerteza , Poluentes Químicos da Água/análise , Qualidade da Água
11.
Environ Sci Pollut Res Int ; 25(25): 25443-25457, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29951762

RESUMO

Surface water and sediment samples were collected from Ajay River basin to appraise the behavior of heavy metals with surrounding environments and their inter-elemental relationships. Parameters like pH and organic carbon are having a minimal role in heavy metal distribution while some elements like Fe and Cu showed great affinity for organic matter based on linear regression analysis (LRA). Ficklin diagram justified that river basin is not contaminated through acidic pollutants. The river basin is highly enriched with Cu, Cd, Pb, and Ni which were much higher than world average values, average shale standard, effect range low (ERL), and threshold effect level (TEL). PCA and LRA verified that Cu, Cd, Pb, and Ni were mainly derived from anthropogenic inputs, and others like Fe, Mn, Zn, and Co came from geogenic sources. Pollution indices revealed that river basin is moderately to highly contaminated by Cu, Cd, and Ni. Furthermore, Ajay River basin is under strong potential ecological risk based on the obtained value of risk index and probable effect level/effect range median quotient index. However, river basin is strongly influenced by lithological properties, diversified hydrogeological settings, mineralization and mobilization of subsurface materials, and urban and industrial effluents which are controlling the heavy metals.


Assuntos
Poluição Ambiental/análise , Sedimentos Geológicos/química , Metais Pesados , Rios/química , Poluentes Químicos da Água , Água/química , Ecologia , Monitoramento Ambiental , Fenômenos Geológicos , Concentração de Íons de Hidrogênio , Índia , Indústrias , Medição de Risco , Poluentes do Solo , Análise Espacial , Abastecimento de Água
12.
Chemosphere ; 204: 501-513, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29679871

RESUMO

Groundwater chemistry of mining region of East Singhbhum district having complex contaminant sources were investigated based on heavy metals loads and other hydrochemical constituents. This study aimed to identify the degree of heavy metals exposure and their potential health risk to local population. The results of hydrochemical analysis showed that Na+, K+, and Ca2+ ions are the dominant cations in the groundwater, while HCO3-, F- and Cl- ions dominate the anionic part of the groundwater. The weathering process was considered the dominant factor to determine the major ionic composition in the study area. Compositional analysis for heavy metal has identified that groundwater of the study area is contaminated by Cd, Pb and Cr elements. Source of these metals have been identified as an anthropogenic inputs from mining activities and mineral processing units. Health risk analysis of individual heavy metal for chronic daily intake (CDI) and hazard quotient (HQ) was found in the order of Cr > As > Cd > Pb which is indicating high health risk for the population. In addition, Hazard Index (HI) analysis for heavy metals was found significantly high (>1) which is considered as a threat for human population because they have the tendency to accumulate in the body and cause variety of diseases like kidney problem, dysfunction of liver and renal cortex as well as cancer.


Assuntos
Monitoramento Ambiental/métodos , Água Subterrânea/química , Metais Pesados/análise , Mineração , Poluentes Químicos da Água/análise , Humanos , Índia , Medição de Risco
13.
Environ Geochem Health ; 40(6): 2259-2301, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29572620

RESUMO

Fluoride contamination in the groundwater has got great attention in last few decades due to their toxicity, persistent capacity and accumulation in human bodies. There are several sources of fluoride in the environment and different pathways to enter in the drinking water resources, which is responsible for potential effect on human health. Presence of high concentration of fluoride ion in groundwater is a major issue and it makes the water unsuitable for drinking purpose. Availability of fluoride in groundwater indicates various geochemical processes and subsurface contamination of a particular area. Fluoride-bearing aquifers, geological factors, rate of weathering, ion-exchange reaction, residence time and leaching of subsurface contaminants are major responsible factors for availability of fluoride in groundwater. In India, several studies have reported that the groundwater of several states are contaminated with high fluoride. The undesirable level of fluoride in groundwater is one of the most natural groundwater quality problem, which affects large portion of arid and semiarid regions of India. Rajasthan, Andhra Pradesh, Telangana, Tamil Nadu, Gujarat, and West Bengal are the relatively high-fluoride-contaminated states in India. Chronic ingestion of high doses of fluoride-rich water leads to fluorosis on human and animal. Over 66 million Indian populations are at risk due to excess fluoride-contaminated water. Therefore, groundwater contamination subject to undesirable level of fluoride needs urgent attention to understand the role of geochemistry, hydrogeology and climatic factors along with anthropogenic inputs in fluoride pollution.


Assuntos
Monitoramento Ambiental , Recuperação e Remediação Ambiental/métodos , Fluoretos/análise , Água Subterrânea/química , Poluentes do Solo/análise , Poluentes Químicos da Água/análise , Poluição Química da Água/prevenção & controle , Humanos , Índia , Medição de Risco
14.
Chemosphere ; 174: 183-199, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28161519

RESUMO

The sources of heavy metals and their loads in the Ajay River were investigated based on the seasonal and spatial variations. To identify variation and pathways of heavy metals, seventy-six water samples were estimated for 2 years at nineteen sampling sites. The multifaceted data were applied to evaluate statistical relation between variables and arithmetic calculation of the indices. Fickling plot suggested that the acidic pollutants do not affect the water quality because all samples lie within the neutral pH range. Further, OC showed significant relation with Fe, Mn, Ni and Co. Compositional analysis identified weathering of rocks, mobility of soil and sediment, atmospheric deposition and numerous anthropogenic inputs as major sources of heavy metals. The mean values of heavy metal pollution index (HPI) and pollution index (PI) were found above the critical index and strong loadings respectively due to higher values of Cd, Pb and Fe. Similarly, assessment of human risk revealed that the high load of Cd, Pb and Fe in water body could harm the population. Majority of the samples showed high concentration of heavy metals as compared to regulatory standard and background values, which suggests that the water is highly contaminated through numerous geogenic and anthropogenic sources.


Assuntos
Sedimentos Geológicos/química , Metais Pesados/análise , Rios/química , Poluentes do Solo/análise , Poluentes Químicos da Água/análise , Adulto , Criança , Monitoramento Ambiental/métodos , Humanos , Índia , Medição de Risco , Pele/efeitos dos fármacos , Qualidade da Água
15.
Chemosphere ; 150: 227-238, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26901480

RESUMO

Considerable lacunae exists in As and F(-) co-contamination investigation in the Brahmaputra and Gangetic floodplains. Therefore we selected Diphu a township in the Karbi Plateau rising from the Brahmaputra floodplains for evaluation of As and F co-occurrence, correlation with coexisting ions of the aquifer system and elucidation of potential processes for releasing As and F(-) in the groundwater. Our initial appraisal used generic plots for identification of hydro geochemical processes and major water types. Subsequently, As and F(-) co-occurrence with pH, depth, HCO3(-), SO4(2-), Ca(2+) and Fe were probed for possible correlation followed by hierarchical cluster analyses to identify key processes for co-occurrence. Finally, saturation indices of groundwater minerals were calculated using MINTEQA2 to elucidate prospective As and F(-) release into groundwater. Results indicate F(-) and As presence in Ca-HCO3 rich water along with positive correlation between Ca(2+) and F(-) possibly due to limestone reserves in adjoining areas. Multivariate analyses suggest the presence of high concentrations of PO4(3-), and H4SiO4 either individually or in combination can enhance the mobility of both As and F(-) and possibly abet conditions conducive for co-contamination of aquifers. Initial release of As and F(-) from the parent rock seems driven by the anthropogenic activities while mobilization depends on chemical interactions and individual affinities of the elements. The results of speciation highlight further mobilization of As and F(-) into the groundwater which in turn require regular attention for sustainable management of scarce water resource present in the area.


Assuntos
Arsênio/análise , Monitoramento Ambiental/métodos , Fluoretos/análise , Água Subterrânea/química , Poluentes Químicos da Água/análise , Análise por Conglomerados , Água Subterrânea/análise , Índia
16.
Future Med Chem ; 7(12): 1535-42, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26334206

RESUMO

Autophagy, a catabolic process, is activated by conditions of stress and nutrient deprivation, which occurs to maintain metabolic homeostasis by performing catabolic lysis of excessive or unnecessary proteins, and injured or aged organelles. Autophagy is regulated by various signaling pathways. Main regulators of autophagy are the PI3K-Akt-mTOR pathway, Beclin1, Bcl-2, Ras and p53. Autophagy plays dual role in cancer, shows both tumor suppressive and oncogenic activity. It is accepted that drug resistance in cancer cells can be overcome by inhibition of autophagy. Herein, we summarize autophagy as a potential target of anticancer drugs and targeting autophagy provides a promising therapeutic strategy to circumvent resistance and enhance the effect of anticancer therapies for cancer patients.


Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Descoberta de Drogas , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Descoberta de Drogas/métodos , Humanos , Terapia de Alvo Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
17.
Curr Drug Targets ; 15(5): 531-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24655140

RESUMO

Excessive production of reactive oxygen species is an important mechanism underlying the pathogenesis of diabetes associated macrovascular and microvascular complications including diabetic nephropathy. Diabetic nephropathy is characterized by glomerular enlargement, early albuminuria and progressive glomerulosclerosis. The pathogenesis of diabetic nephropathy is multi-factorial and the precise mechanisms are unclear. Hyperglycemia-mediated dysregulation of various pathways either enhances the intensity of oxidative stress or these pathways are affected by oxidative stress. Thus, oxidative stress has been considered as a central mediator in progression of nephropathy in patients with diabetes. In this review, we have focused on current perspectives in oxidative stress signaling to determine common biological processes whereby diabetes-induced oxidative stress plays a central role in progression of diabetic nephropathy.


Assuntos
Nefropatias Diabéticas/patologia , Estresse Oxidativo , Animais , Nefropatias Diabéticas/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
18.
Vascul Pharmacol ; 58(4): 259-71, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23313806

RESUMO

Diabetes mellitus is known to trigger retinopathy, neuropathy and nephropathy. Diabetic nephropathy, a long-term major microvascular complication of uncontrolled hyperglycemia, affects a large population worldwide. Recent findings suggest that numerous pathways are activated during the course of diabetes mellitus and that these pathways individually or collectively play a role in the induction and progression of diabetic nephropathy. However, clinical strategies targeting these pathways to manage diabetic nephropathy remain unsatisfactory, as the number of diabetic patients with nephropathy is increasing yearly. To develop ground-breaking therapeutic options to prevent the development and progression of diabetic nephropathy, a comprehensive understanding of the molecular mechanisms involved in the pathogenesis of the disease is mandatory. Therefore, the purpose of this paper is to discuss the underlying mechanisms and downstream pathways involved in the pathogenesis of diabetic nephropathy.


Assuntos
Diabetes Mellitus/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Hiperglicemia/complicações , Animais , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/prevenção & controle , Progressão da Doença , Humanos , Hiperglicemia/etiologia , Hiperglicemia/fisiopatologia , Transdução de Sinais
19.
Braz. j. pharm. sci ; 49(1): 175-184, Jan.-Mar. 2013. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-671413

RESUMO

A stability-indicating high-performance liquid chromatographic (HPLC) method was developed with short run time and validated for the assay of process related impurities of pantoprazole in bulk form. Resolution of drug, its potential impurities and degradation products were achieved on a Hypersil ODS column utilizing a gradient with 0.01 M phosphate buffer of pH 7 and acetonitrile as eluent, at the detection wavelength of 290 nm. Flow rate was set at 1 mL min-1. The procedure was found to be specific, linear (r=0.999), recovery (97.9-103%), LOD (0.043-0.047 µgmL-1), LOQ (0.13-0.14 µgmL-1) and robust. Acceptable robustness indicates that the assay method remains unaffected by small but deliberate variations. Pantoprazole was found to degrade in acidic, oxidative and under photolytic stress conditions. The drug was stable to alkaline and dry heat conditions. This method has been successively applied to pharmaceutical formulation and no interference from the excipients was found.


Desenvolveu-se método indicador de estabilidade por Cromatografia a Líquido de Alta Eficiência (CLAE) com pequeno tempo de corrida e validado para o ensaio de impurezas relacionadas ao processo de produção de pantoprazol em batelada. A determinação do fármaco, de suas impurezas potenciais e dos produtos de degradação foi realizada com coluna de ODS Hypersil, utilizando gradiente com tampão de fosfato 0,01 M pH 7 e acetonitrila como eluente, no comprimento de onda de detecção de 290 nm. A velocidade de fluxo foi fixada em 1 mLmin-1. O procedimento se mostrou específico, linear (r=0,999), com recuperação (97,9-103%), LOD (0,043-0,047 µgmL-1), LOQ (0,13-0,14 µg mL-1) e robusto. Robustez aceitável indica que o método de ensaio não é afetado por variações pequenas, exceto as planejadas. O pantoprazole degradou em condições ácidas, oxidativas e sob condições de estresse fotolítico. O fármaco foi estável em condições alcalinas e de calor seco. Este método tem sido sucessivamente aplicado à formulação farmacêutica e não se encontrou interferência de excipientes.


Assuntos
/análise , Cromatografia Líquida/métodos , /métodos , Estabilidade de Medicamentos
20.
Environ Monit Assess ; 141(1-3): 309-21, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17899419

RESUMO

In present study focus has been given on estimating quality and toxicity of waste with respect to heavy metals and its impact on groundwater quality, using statistical and empirical relationships between different hydrochemical data, so that easy monitoring may be possible which in turn help the sustainable management of landfill site and municipal solid waste. Samples of solid waste, leachate and groundwater were analyzed to evaluate the impact of leachates on groundwater through the comparison of their hydrochemical nature. Results suggest the existence of an empirical relationship between some specific indicator parameters like heavy metals of all three above mentioned sample type. Further, K/Mg ratio also indicates three groundwater samples heavily impacted from leachate contamination. A good number of samples are also showing higher values for NO(3)(-) and Pb than that of World Health Organization (WHO) drinking water regulation. Predominance of Fe and Zn in both groundwater and solid waste samples may be due to metal plating industries in the area. Factor analysis is used as a tool to explain observed relation between numerous variables in term of simpler relation, which may help to deduce the strength of relation. Positive loading of most of the factors for heavy metal clearly shows landfill impact on ground water quality especially along the hydraulic gradient. Cluster analysis, further substantiates the impact of landfill. Two major groups of samples obtained from cluster analysis suggest that one group comprises samples that are severely under the influence of landfill and contaminated leachates along the groundwater flow direction while other assorted with samples without having such influence.


Assuntos
Eliminação de Resíduos , Poluentes Químicos da Água/análise , Análise por Conglomerados , Análise Fatorial , Índia
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