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1.
J Pediatr Clin Pract ; 13: 200114, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39035054

RESUMO

Extreme cold in February 2021 precipitated prolonged power failure in Texas. In Houston, many patients presented for carbon monoxide exposure from neighborhoods with lower per capita income, higher rates of limited English proficiency, and greater median Social Vulnerability Indices than Greater Houston. Weather-related disasters disproportionately affect socially vulnerable communities.

2.
Indian J Cancer ; 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38090957

RESUMO

BACKGROUND: Current markers (carcinoembryonic antigen [CEA] and carbohydrate antigen 15-3 [CA15-3]) lack sensitivity in diagnosis of breast cancer. The aberrantly expressed circulating miRNAs were shown as diagnostic markers in breast cancer. However, there are very few studies from the Indian population. We studied the diagnostic utility of miRNA-21, miRNA-155 and miRNA-205 compared to CEA and CA15-3 in stage I and II breast cancer patients. MATERIALS AND METHODS: Sixty newly diagnosed women with stage I/II breast cancer and 20 healthy controls were recruited. Expression of circulating miRNAs was studied using reverse transcription-polymerase chain reaction, whereas CEA and CA 15-3 were analyzed by enzyme-linked immunosorbent assay. RESULTS: miRNA-21 and miRNA-155 were upregulated, miRNA-205 down-regulated (P < 0.05) and serum CEA and CA15-3 levels increased in breast cancer patients (P < 0.001). Receiver operating characteristic curve analysis showed significant area under curve (AUC) for all markers (0.656 to 0.993; P = 0.015 to <0.001) validating their diagnostic potential. Unlike CEA and CA15-3, miRNAs retained their sensitivity even at higher cut-offs (95% CI of mean). Logistic regression analysis showed significant association between disease and marker positivity for miRNA-21 and miRNA-205 but not for miRNA-155. Combining CA15-3 with miRNAs did not improve their diagnostic performance. However, combining CEA with either miRNA-21 (AUC = 0.742; P < 0.001 versus AUC = 0.656; P = 0.018) or miRNA-205 (AUC = 0.733; P < 0.001 versus AUC = 0.700; P < 0.001) increased its diagnostic performance. CONCLUSION: Our study shows miRNA-21 and miRNA-205, are useful as diagnostic markers for breast cancer in the Indian population and combination of these miRNAs with CEA but not with CA 15-3 improved their diagnostic performance.

3.
J Fluoresc ; 33(5): 2023-2039, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36971980

RESUMO

1,3,4-Oxadiazole pharmacophore is still considered a viable biologically active scaffold for the synthesis of more effectual and broad-spectrum antimicrobial agents. Therefore, the present study is based on five 1,3,4-oxadiazole target structures, viz., CAROT, CAROP, CARON (D-A-D-A systems) and NOPON and BOPOB (D-A-D-A-D systems) bearing various bioactive heterocyclic moieties relevant to potential biological activities. Three of the compounds, CARON, NOPON and BOPOB were assessed in-vitro for their efficacy as antimicrobial agents against gram positive (Staphylococcus aureus and Bacillus cereus) and gram negative (Escherichia coli and Klebsiella pneumonia) bacteria; and two fungi, Aspergillus niger and Candida albicans; also, as an anti-tuberculosis agent against Mycobacterium tuberculosis. Most of the tested compounds displayed promising antimicrobial activity, especially CARON which was then analyzed for the minimum inhibitory concentration (MIC) studies. Similarly, NOPON portrayed the highest anti-TB activity among the studied compounds. Consequently, to justify the detected anti-TB activity of these compounds and to recognize the binding mode and important interactions between the compounds and the ligand binding site of the potential target, these compounds were docked into the active binding site of cytochrome P450 CYP121 enzyme of Mycobacterium tuberculosis, 3G5H. The docking results were in good agreement with the result of in-vitro studies. In addition, all the five compounds were tested for their cell viability and have been investigated for cell labeling applications. To conclude, one of the target compounds, CAROT was used for the selective recognition of cyanide ion by 'turn-off' fluorescent sensing technique. The entire sensing activity was examined by spectrofluorometric method and MALDI spectral studies. The limit of detection obtained was 0.14 µM.


Assuntos
Anti-Infecciosos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Oxidiazóis/farmacologia , Fungos , Bactérias , Testes de Sensibilidade Microbiana , Antibacterianos/química , Relação Estrutura-Atividade , Antifúngicos/química
4.
J Family Med Prim Care ; 11(12): 7783-7787, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36994028

RESUMO

Background: The reproductive, maternal, newborn, child + adolescent health (RMNCH+A) strategy was launched by the Indian government in the year 2013 to remain in the lead of the global war against child and maternal mortality and morbidity. Under RMNCH+A program in Uttarakhand state, according to the State public health policy, various provisions are needed to be done for maintenance of downtrend in infant mortality rate (IMR). There are various thrust areas under the child health program. The purpose of our study is to monitor the program implementation in terms of Input and Process indicators and to identify if there are any gaps in the child health services provided by RMNCH+A in the PHCs and subcentres of Doiwala block of Dehradun district, Uttarakhand. Aim: To evaluate Input and the process indicators of child health services under RMNCH+A strategy at Primary health care level in Doiwala block of Dehradun district, Uttarakhand. Methods: This Cross-sectional study was carried out in Doiwala Block of Dehradun district, Uttarakhand in 3 randomly selected Primary health centres (PHCs) and their 6 subcentres using a validated standard checklist for PHCs and subcentres. Results: In PHCs, mean obtained score for Input indicators was 56% and for Process indicators was 35%. The mean obtained score in subcentres for Input indicators and Process indicators was 53% and 51%, respectively. Conclusions: Both the input and the process indicators for child health services in PHCs and subcentres of Dehradun district were inadequate. Most indicators scored less than 50% at both the PHCs and subcentres.

5.
Environ Sci Pollut Res Int ; 28(24): 31013-31031, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33594572

RESUMO

With the use of different multivariate statistical analysis methods, spatio-temporal fluctuations in the water parameters of Tiru reservoir located at the Marathwada drought-prone area of Maharashtra, India, have been analysed and reported in this case study. Tiru reservoir, situated on the tributary of the Godavari River, was regularly monitored at five different sites from August 2017 to January 2019 for the estimation of 20 water quality parameters. Various multivariate methods such as pattern reorganisation using cluster analysis (CA), factor analysis/principal component analysis (FA/PCA), and discriminant analysis (DA) were used for handling complex datasets. CA extracted three different clusters from five sampling sites with similar water quality characteristics. FA/PCA extracted thirteen factors (65% of 20 measured) required to explain 74% of the data variability and identified the factors accountable for variation in water quality and also evaluated the prevalence of each cluster on the overall dissimilarity at five different sampling sites. Discriminant analysis extracted a total of 16 parameters with 97.7% right assignations. Varifactors (VFs) acquired by factor analysis recommended that the water quality parameters accounted for variation were linked to two groups. The first group included water quality parameters like T, DO, SDD, turbidity, TDS, PA, and MA, whereas the second group covered most of the nutrients Cl-, silicates, PP, TP, NO3-N, NO2-N, and NH3-N; hardness; and CHL-a and mainly entered the reservoir during surface runoff from agriculture fields and the surrounding area containing domestic as well as animal waste. Thus, the present work showed the efficiency of multivariate methods for the assessment of spatial as well as a temporal variation in the water quality of a small reservoir.


Assuntos
Poluentes Químicos da Água , Qualidade da Água , Análise por Conglomerados , Secas , Monitoramento Ambiental , Índia , Análise de Componente Principal , Rios , Estações do Ano , Poluentes Químicos da Água/análise
6.
Zootaxa ; 4652(1): zootaxa.4652.1.11, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31716891

RESUMO

Macrobrachium indicum, a south Indian freshwater prawn described from Vellayani lake, Kerala is closely related to Koua river prawn, M. australe which in turn resembles M. ustulatum. Morphologically the three species pose difficulties in identification. A comparison of morphological characters of M. indicum, M. australe and M. ustulatum has been made in the paper. The COI sequence data for the species has been generated and made comparison with the existing COI barcode sequences for M. australe and showed clear difference between the species, thereby established the taxonomic validity of the species. Alignment of the present study sequences with reported sequences of M. australe revealed homologous region of 434 bp. Out of 434 nucleotides, the number of conserved and variable nucleotides were 313 and 121, respectively. Based on the P value (0.002) of Mann-Whitney U test, it was observed that the GC content at codon third base position between M. indicum and M. australe is significantly different. Because of the complexity of the species group a type material is highly necessary for confirmation in future studies and since holotype is irrecoverably lost, a neotype has been selected from the present collection and deposited in the CMFRI Museum at Kochi, Kerala with accession number: ED.2.2.1.8.


Assuntos
Palaemonidae , Animais , Lagos , Filogenia
7.
Mol Biol Rep ; 46(6): 6287-6297, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31538300

RESUMO

Single nucleotide polymorphisms (SNPs) in adiponectin gene [rs1501299 (+276G/T) and rs266729 (-11377C/G)] and one SNP of leptin gene [rs7799039 (-2548G/A)] are known to influence plasma levels of adiponectin and leptin respectively. Literature is scarce on the association of adiponectin gene polymorphism rs266729 with breast cancer. The present study was taken up to study these polymorphisms and their association with breast cancer. Ninety-three patients diagnosed with malignant breast cancer were included as cases along with 186 age matched healthy controls. Adiponectin +276G/T, -11377C/G and leptin -2548G/A polymorphism were studied using polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). Adipokine levels in blood were measured using enzyme linked immunosorbent assay. Adiponectin +276G/T and leptin -2548G/A showed a significant increased risk for breast cancer even after adjusting for confounding variables like present age, age at menarche, age at first child birth and age at menopause. In the subset analysis, based on menopausal state, stronger association was observed between SNP in adiponectin gene +276G/T with the breast cancer in post-menopausal women after adjusting for all other variables. No association was found with adiponectin -11377C/G. No association of the gene polymorphisms with adipokine levels was observed. Also, no significant association was seen for the effect of gene-environment interaction i.e. presence of polymorphism with obesity and menopausal state for any of the SNPs studied. Adiponectin +276G/T is strongly associated with breast cancer in postmenopausal women while leptin -2548G/A polymorphisms is significantly associated with breast cancer irrespective of the menopausal state in south Indian subjects.


Assuntos
Adiponectina/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença , Leptina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Feminino , Frequência do Gene , Interação Gene-Ambiente , Estudos de Associação Genética , Genótipo , Humanos , Mamografia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Risco
8.
Environ Monit Assess ; 191(9): 586, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31440835

RESUMO

Lakes and reservoirs around the world are facing a substantial water quality degradation problem that poses significant environmental, social, and economic impacts. Reservoir productivity is influenced primarily by the climatic, morphometric, and hydro-edaphic features. High nutrient loadings in the reservoir from agriculture runoff often provide ideal conditions for algal blooms, leading to eutrophication. Reservoir and lake management to prevent or reduce eutrophication, therefore, has become the need of the hour. The traditional approach of trophic state monitoring by rigorous field surveys and eutrophication modeling has been revised in the present study by developing a new trophic state index (TSI)-based model for tropical shallow freshwater reservoirs. The new model has been constructed based on Carlson's Limnology and Oceanography, 22, 361-369, (1977) guidelines by establishing an empirical relationship between trophic parameters including total phosphorus (TP), Secchi disk depth (SDD), and chlorophyll (Chl-a). After comparing the new model with various earlier models for its applicability and validation with actual field conditions, it was found to be most precise over previous TSI models. Temporal and spatial fluctuations in the water quality of the Tiru reservoir were primarily attributed to the changing climatic conditions during the study period. Seasonal monsoon with less frequency, heavy nutrient loading from agriculture runoff, and increased turbidity due to a high level of sediment inflow during monsoon raised the TSI (SDD) values of the Tiru reservoir to place it in the hyper-eutrophic class. Average TSI values during winter for SDD, Chl-a, and TP were indicative of the meso-eutrophic to eutrophic state. Saturation of nutrients due to low water level during summer season caused the poly-eutrophic condition for TSI (SDD)- and TSI (TP)-based estimates and eutrophic condition as per TSI (Chl-a) estimates. However, seasonal deviations of the TSI values based on the relationship between TSI (Chl-a) and TSI (SD) indicated a predominance of smaller particles (non-algal turbidity) during all seasons. Even though TP present in the Tiru reservoir is controlling the algal production, it is also affected by low-light conditions due to non-algal turbidity. The recommendation from this study is that the TSI method for estimating the health of the water bodies is the efficient, cost-effective, and time-saving approach. The model developed during the study would help managers and policy makers to take necessary steps to reduce eutrophication levels in the reservoir and would be helpful for researchers in developing new concepts and protocols, mainly focusing on shallow freshwater reservoirs.


Assuntos
Clorofila/análise , Monitoramento Ambiental/métodos , Eutrofização/fisiologia , Fósforo/análise , Poluentes Químicos da Água/análise , Agricultura , Clima , Lagos/química , Modelos Teóricos , Estações do Ano , Qualidade da Água , Abastecimento de Água
9.
J Pharmacol Exp Ther ; 364(1): 145-155, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29054857

RESUMO

Benzodiazepines are commonly prescribed anxiolytics that pose abuse liability in susceptible individuals. Although it is well established that all drugs of abuse increase brain dopamine levels, and benzodiazepines are allosteric modulators of the GABAA receptor, it remains unclear how they alter dopamine release. Using in vivo fast-scan cyclic voltammetry, we measured diazepam-induced changes in the frequency and amplitude of transient dopamine release events. We found that diazepam concurrently increases the frequency and decreases the amplitude of transient dopamine release events in the awake and freely moving rat. The time course during which diazepam altered the frequency and amplitude of dopamine release events diverged, with the decreased amplitude effect being shorter lived than the increase in frequency, but both showing similar rates of onset. We conclude that diazepam increases the frequency of accumbal dopamine release events by disinhibiting dopamine neurons, but also decreases their amplitude. We speculate that the modest abuse liability of benzodiazepines is due to their ability to decrease the amplitude of dopamine release events in addition to increasing their frequency.


Assuntos
Diazepam/farmacologia , Dopamina/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Animais , Flumazenil/farmacologia , Masculino , Ratos , Fatores de Tempo
10.
PLoS Negl Trop Dis ; 9(7): e0003942, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26201090

RESUMO

BACKGROUND: Rabies is a fatal encephalitis caused by viruses belonging to the genus Lyssavirus of the family Rhabdoviridae. It is a viral disease primarily affecting mammals, though all warm blooded animals are susceptible. Experimental rabies virus infection in birds has been reported, but naturally occurring infection of birds has been documented very rarely. PRINCIPAL FINDINGS: The carcass of a domestic fowl (Gallus domesticus), which had been bitten by a stray dog one month back, was brought to the rabies diagnostic laboratory. A necropsy was performed and the brain tissue obtained was subjected to laboratory tests for rabies. The brain tissue was positive for rabies viral antigens by fluorescent antibody test (FAT) confirming a diagnosis of rabies. Phylogenetic analysis based on nucleoprotein gene sequencing revealed that the rabies virus strain from the domestic fowl belonged to a distinct and relatively rare Indian subcontinent lineage. SIGNIFICANCE: This case of naturally acquired rabies infection in a bird species, Gallus domesticus, being reported for the first time in India, was identified from an area which has a significant stray dog population and is highly endemic for canine rabies. It indicates that spill over of infection even to an unusual host is possible in highly endemic areas. Lack of any clinical signs, and fewer opportunities for diagnostic laboratory testing of suspected rabies in birds, may be the reason for disease in these species being undiagnosed and probably under-reported. Butchering and handling of rabies virus- infected poultry may pose a potential exposure risk.


Assuntos
Galinhas , Doenças das Aves Domésticas/virologia , Vírus da Raiva/isolamento & purificação , Raiva/veterinária , Animais , Antígenos Virais/isolamento & purificação , Encéfalo/virologia , Índia/epidemiologia , Nucleoproteínas/genética , Nucleoproteínas/metabolismo , Filogenia , Doenças das Aves Domésticas/diagnóstico
11.
J Control Release ; 162(2): 429-37, 2012 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-22841795

RESUMO

It is well appreciated that delivery of therapeutic agents through the pulmonary route could provide significant improvement in patient compliance and reduce systemic toxicity for a variety of diseases. Many inhalable drug formulations suffer from low respirable fractions, rapid clearance by alveolar macrophages, target non-specificity, and difficulty in combining aerodynamic properties with efficient cellular uptake. To overcome these challenges, we developed an enzyme-responsive, nanoparticle-in-microgel delivery system. This system is designed to provide optimal aerodynamic carrier size for deep lung delivery, improved residence time of carriers in the lungs by avoiding rapid clearance by macrophages, and reduction of side effects and toxicity by releasing encapsulated therapeutics in response to disease-specific stimuli. This unique carrier system is fabricated using a new Michael addition during (water-in-oil) emulsion (MADE) method, especially suitable for biologic drugs due to its gentle fabrication conditions. The resulting microgels have a highly porous internal structure and an optimal aerodynamic diameter for effective deep lung delivery. They also exhibit triggered release of various nanoparticles and biologics in the presence of physiological levels of enzyme. In addition, the nanoparticle-carrying microgels showed little uptake by macrophages, indicating potential for increased lung residence time and minimal clearance by alveolar macrophages. Collectively, this system introduces a rationally designed, disease-specific, multi-tiered delivery system for use as an improved pulmonary carrier for biologic drugs.


Assuntos
Portadores de Fármacos/administração & dosagem , Composição de Medicamentos/métodos , Pulmão/metabolismo , Nanopartículas/administração & dosagem , Administração por Inalação , Animais , Linhagem Celular , Linhagem Celular Tumoral , DNA/administração & dosagem , DNA/química , Portadores de Fármacos/química , Géis , Células HEK293 , Humanos , Hidrólise , Imunoglobulina G/administração & dosagem , Imunoglobulina G/química , Camundongos , Nanopartículas/química , Oligopeptídeos/química , Tamanho da Partícula , Polietilenoglicóis/química , Tripsina/metabolismo
12.
Stem Cell Rev Rep ; 6(4): 585-600, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20665129

RESUMO

The differentiation and proliferation of neural stem/progenitor cells (NPCs) depend on various in vivo environmental factors or cues, which may include an endogenous electrical field (EF), as observed during nervous system development and repair. In this study, we investigate the morphologic, phenotypic, and mitotic alterations of adult hippocampal NPCs that occur when exposed to two EFs of estimated endogenous strengths. NPCs treated with a 437 mV/mm direct current (DC) EF aligned perpendicularly to the EF vector and had a greater tendency to differentiate into neurons, but not into oligodendrocytes or astrocytes, compared to controls. Furthermore, NPC process growth was promoted perpendicularly and inhibited anodally in the 437 mV/mm DC EF. Yet fewer cells were observed in the DC EF, which in part was due to a decrease in cell viability. The other EF applied was a 46 mV/mm alternating current (AC) EF. However, the 46 mV/mm AC EF showed no major differences in alignment or differentiation, compared to control conditions. For both EF treatments, the percent of mitotic cells during the last 14 h of the experiment were statistically similar to controls. Reported here, to our knowledge, is the first evidence of adult NPC differentiation affected in an EF in vitro. Further investigation and application of EFs on stem cells is warranted to elucidate the utility of EFs to control phenotypic behavior. With progress, the use of EFs may be engineered to control differentiation and target the growth of transplanted cells in a stem cell-based therapy to treat nervous system disorders.


Assuntos
Eletricidade , Hipocampo/citologia , Neurônios/citologia , Células-Tronco/citologia , Animais , Contagem de Células , Movimento Celular/fisiologia , Proliferação de Células , Imuno-Histoquímica , Ratos , Ratos Endogâmicos F344
13.
Trop Biomed ; 25(1): 87-92, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18600209

RESUMO

This paper presents the first reported use of 18S rRNA gene sequence to determine the phylogeny of Brugia pahangi. The 18S rRNA nucleotide sequence of a Malaysian B. pahangi isolate was obtained by PCR cloning and sequencing. The sequence was compared with 18S rRNA sequences of other nematodes, including those of some filarial nematodes. Multiple alignment and homology analysis suggest that B. pahangi is closely related to B. malayi and Wuchereria bancrofti. Phylogenetic trees constructed using Neighbour Joining, Minimum Evolution and Maximum Parsimony methods correctly grouped B. pahangi with other filarial nematodes, with closest relationship with B. malayi and W. bancrofti. The phylogeny of B. pahangi obtained in this study is in concordance with those previously reported, in which the 5S rRNA gene spacer region and cytochrome oxidase subunit I (COI) sequences were used.


Assuntos
Brugia pahangi , Filogenia , RNA Ribossômico 18S/genética , Análise de Sequência de DNA , Animais , Sequência de Bases , Brugia pahangi/classificação , Brugia pahangi/genética , DNA de Helmintos/análise , Filariose/parasitologia , Dados de Sequência Molecular , Alinhamento de Sequência
14.
Biochem Pharmacol ; 75(7): 1472-81, 2008 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-18242581

RESUMO

Aspirin exerts its unique pharmacological effects by irreversibly acetylating a serine residue in the cyclooxygenase site of prostaglandin-H2-synthases (PGHSs). Despite the irreversibility of the inhibition, the potency of aspirin varies remarkably between cell types, suggesting that molecular determinants could contribute to cellular selectivity. Using purified enzymes, we found no evidence that aspirin is selective for either of the two PGHS isoforms, and we showed that hydroperoxide substrates of the PGHS peroxidase inhibited the rate of acetylation of PGHS-1 by 68%. Using PGHS-1 reconstituted with cobalt protoporphyrin, a heme devoid of peroxidase activity, we demonstrated that reversal by hydroperoxides of the aspirin-mediated acetylation depends upon the catalytic activity of the PGHS peroxidase. We demonstrated that inhibition of PGHS-2 by aspirin in cells in culture is reversed by 12-hydroperoxyeicosatetraenoic acid dose-dependently (ED50=0.58+/-0.15 microM) and that in cells with high levels of hydroperoxy-fatty acids (RAW264.7) the efficacy of aspirin is markedly decreased as compared to cells with low levels of hydroperoxides (A549; IC50s=256+/-22 microM and 11.0+/-0.9 microM, respectively). Together, these findings indicate that acetylation of the PGHSs by aspirin is regulated by the catalytic activity of the peroxidase, which yields a higher oxidative state of the enzyme.


Assuntos
Aspirina/farmacologia , Ciclo-Oxigenase 2/metabolismo , Peroxidase/metabolismo , Acetilação/efeitos dos fármacos , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/enzimologia , Bovinos , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Humanos , Camundongos , Oxirredução/efeitos dos fármacos , Ovinos
15.
Bioconjug Chem ; 15(6): 1230-5, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15546188

RESUMO

A series of acridinium derivatives 1-6, wherein steric factors have been varied systematically through substitution at the 9 position of the acridine ring, have been synthesized and their DNA interactions have been investigated by various biophysical techniques. The unsubstituted and methylacridinium derivatives 1 and 2 and the o-tolylacridinium derivative 6 exhibited high fluorescence quantum yields (Phi(f)() congruent with 1) and lifetimes (tau = 35, 34, and 25 ns, respectively), when compared with the arylacridinium derivatives 3-5. The acridinium derivatives 1 and 2 showed high DNA binding affinity (K = 7.3-7.7 x 10(5) M(-)(1)), when compared to the arylacridinium derivatives 3-5 (K = 6.9-10 x 10(4) M(-)(1)). DNA melting and viscosity studies establish that in the case of the aryl-substituted systems, the efficiency of DNA binding is in the order, phenyl > p-tolyl > m-tolyl >>>> o-tolyl derivative. The increase in steric crowding around the acridine ring hinders the DNA binding interactions and thereby leads to negligible binding as observed in the case of 6 (o-tolyl derivative). These results indicate that a subtle variation in the substitution pattern has a profound influence on the photophysical and DNA interactions. Further, they demonstrate that pi-stacking interactions of the ligands with DNA are essential for efficient electron transfer between the DNA bases and the ligands. These water soluble and highly fluorescent molecules which differ in their DNA binding mode can act as models to study various DNA-ligand interactions.


Assuntos
Acridinas/química , DNA/química , Substâncias Intercalantes/química , Acridinas/metabolismo , DNA/metabolismo , Transporte de Elétrons/fisiologia , Substâncias Intercalantes/metabolismo , Conformação Molecular , Ligação Proteica/fisiologia
16.
Int J Rehabil Res ; 27(1): 71-4, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15097173

RESUMO

Early ambulation after lower extremity amputation has profound benefits on the functional, psychological outcomes and enhanced prosthetic compliance among this clientele. The various potential risks of immobility--pain, oedema, muscle atrophy, phantom sensations, contractures, aerobic de-conditioning, and the like, are reduced due to early ambulation. Moreover, it assists in accelerated wound healing, preservation of postural reflexes and, above all, achievement of better psychological well-being. Though such benefits have been observed in the history of prosthetic rehabilitation, a cost-effective prosthesis for such an early management among Third World nations is still unavailable. Therefore, this article is an attempt to present an indigenously developed temporary prosthesis designed to make the above benefits possible at a lower cost. This prosthesis helps in myriad ways--immediate prosthetic fitting, early weight bearing, early ambulation--and also has the added advantage of being adjustable to anthropological variations. The ischial weight bearing, lateral opening socket reduces the pressure and shear over the stump, thus avoiding stump complications. This increases the prosthetic acceptance by the client due to early involvement in the rehabilitation. Above all, it is cost effective and comfortable, thus enhancing compliance and superior outcome in prosthetic rehabilitation, especially among the clients in Third World nations.


Assuntos
Amputação Cirúrgica/reabilitação , Membros Artificiais/economia , Deambulação Precoce , Análise Custo-Benefício , Países em Desenvolvimento , Deambulação Precoce/economia , Humanos , Desenho de Prótese
17.
J Appl Toxicol ; 20(4): 327-34, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10942908

RESUMO

Gulf War veterans were taking pyridostigmine orally against possible exposure to nerve agents as well as being under physical stress. This study was designed to investigate the delayed effects of pyridostigmine and treadmill exercise on cholinesterase activity, lipid peroxidation and histology of peripheral tissues of mice. Male NIH Swiss mice were divided into four groups of 15 animals each and treated as follows: sedentary control; exercise training for 10 weeks; pyridostigmine (1.2 mg kg(-1), p.o.) for 2 weeks during weeks 5 and 6; and pyridostigmine plus exercise training. The mice were sacrificed 24 h after the last exercise, and blood, triceps muscle and sciatic nerve were isolated and analyzed. The group treated with pyridostigmine alone showed decreased plasma butyrylcholinesterase (BChE) activity (87% of control), whereas pyridostigmine plus exercise significantly decreased the BChE activity (79% of control), indicating an interactive effect of the combination. Acetylcholinesterase (AChE) activity did not alter significantly in red blood cells, platelets or sciatic nerve with either of the treatments. However, AChE activity in triceps muscle decreased significantly (78% of control) in the group treated with pyridostigmine plus exercise. Creatine phosphokinase activity in plasma increased slightly (compared to control, pyridostigmine or exercise group) in mice treated with pyridostigmine plus exercise, which may be indicative of perturbation in the integrity of the skeletal muscle due to combination. However, there were no obvious histological abnormalities in the triceps muscle detected between experimental and control groups. Interaction of pyridostigmine and exercise significantly increased the concentration of the end product of lipid peroxidation (malondialdehyde) (124% of control) in triceps muscle, indicating an oxidative stress response of the combination. These results indicate that physical stress enhanced the delayed toxic effects of a subchronic oral dose of pyridostigmine primarily in the skeletal muscle of mice.


Assuntos
Inibidores da Colinesterase/toxicidade , Brometo de Piridostigmina/toxicidade , Estresse Fisiológico/enzimologia , Acetilcolinesterase/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Animais , Butirilcolinesterase/efeitos dos fármacos , Butirilcolinesterase/metabolismo , Creatina Quinase/efeitos dos fármacos , Creatina Quinase/metabolismo , Preparações de Ação Retardada , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Músculos/efeitos dos fármacos , Músculos/enzimologia , Condicionamento Físico Animal/fisiologia , Estresse Fisiológico/metabolismo
18.
Neurol India ; 44(1): 16-21, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-29542649

RESUMO

A case of chronic sensory ataxic neuropathy secondary to primary polycythemia is reported. This association, has not been recorded before. Electrophysiological investigations revealed features consistent with severe sensory and mild motor axonopathy. Sural nerve biopsy showed severe fibre loss and Schwann cell proliferation. Ultra structurally accumulation of neurofilaments was noted in both unmyelinated and myelinated fibres. Low persistent ischaemia of nerves due to hyperviscosity is the probablepathogenic mechanism for the axonal stasis and nerve damage.

19.
Epilepsia ; 34(3): 476-87, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8389290

RESUMO

Twenty-one cases (12 males, 9 females) of Lafora's disease in 16 families were studied at the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India, from 1982 to 1990. Mean age of onset was 13.5 years (range 9.5-18 years). First symptom was generalized tonic-clonic seizure (17), myoclonus (3), or dementia (1). All patients eventually developed the classical triad, except 1 who has had only myoclonus. Seven had occipital seizures. Other signs included behavioral changes (9), brisk tendon reflexes (11), cerebellar signs (8), and visual impairment (4). Patients from 14 of the 16 families (85%) were products of consanguineous marriage. More than 1 sibling was affected in 6 families. Scalp EEGs showed diffuse background slowing with epileptiform discharges in all and progressive slowing as the disease progressed in 3. Photosensitivity occurred in 4 of the 17 cases studied (23.5%). EEG abnormalities were documented in the presymptomatic stage in 2 cases 6 months and 6 years before clinical symptom onset. Visual evoked responses were abnormal in 4 of the 6 cases studied. Giant somatosensory evoked potentials (SSEP) were observed in all 8 cases studied. Lafora bodies were demonstrated in axillary skin in 14 of 17 (82.4%), in liver in 4 of 10 (40%), and in both brain biopsy specimens. In 2 cases, liver biopsy was positive while axillary skin biopsy was negative. In the brain, inclusions were evident in glial and capillary endothelial cells in addition to neurons. Although our cases were similar to those described earlier, the relative rarity of visual phenomena is emphasized. The clinical pattern was consistent with autosomal recessive inheritance. The high frequency of consanguinity in the South Indian population may be responsible for the many cases observed at our center.


Assuntos
Epilepsias Mioclônicas/diagnóstico , Adolescente , Adulto , Encéfalo/patologia , Criança , Eletroencefalografia , Epilepsias Mioclônicas/epidemiologia , Epilepsias Mioclônicas/genética , Potenciais Evocados , Família , Feminino , Humanos , Corpos de Inclusão/patologia , Índia/epidemiologia , Fígado/patologia , Masculino , Linhagem
20.
Neurosurgery ; 25(6): 982-6, 1989 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2601832

RESUMO

We report a case of Balo's concentric sclerosis, a rare and acute variant of multiple sclerosis, which coexisted with an oligodendroglioma. The demyelinating lesion was clinically silent and was detected at necropsy. The pathogenesis of concentric sclerosis and the relationship of the demyelinating lesion to the evolution of the glial neoplasm is briefly discussed.


Assuntos
Neoplasias Encefálicas/complicações , Esclerose Múltipla/complicações , Oligodendroglioma/complicações , Adulto , Neoplasias Encefálicas/patologia , Feminino , Humanos , Esclerose Múltipla/patologia , Oligodendroglioma/patologia
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