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2.
Indian Pediatr ; 56(4): 294-298, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31064897

RESUMO

BACKGROUND: In preterm neonates, enteral feeding is advanced slowly, considering the risk of necrotizing enterocolitis. Prolonged intravenous alimentation in these neonates, however, may increase the risk of sepsis-related morbidity and mortality, particularly in low resource settings. OBJECTIVES: Objective of this was study to evaluate impact of aggressive enteral feeding on mortality and morbidities among preterm neonates. DESIGN: Randomized controlled trial. PARTICIPANTS: Neonates with birthweight 750-1250 g. INTERVENTIONS: 131 preterm neonates with birth weight 750-1250 g, admitted to neonatal intensive care unit between April 2012 and June 2014, were randomized to aggressive feeding or conservative feeding regimen. OUTCOMES: The primary outcome of the study was all-cause mortality during hospital stay. The secondary outcomes included proportion of sepsis (blood culture proven), necrotizing enterocolitis, feed intolerance, survival without major morbidity at discharge, time to reach full enteral feed (180 mL/kg/d), duration of hospitalization, and average daily weight gain (g/kg). RESULTS: All-cause mortality was 33.3% in aggressive regimen and 43.1% in conservative regimen, [RR (95%) CI 0.77 (0.49, 1.20)]. Neonates with aggressive feeding regimen reached full enteral feed earlier; median (IQR) 7 (6, 8) days compared to conservative regimen, 10 (9, 14) days; P <0.001. There was no difference in culture positive sepsis rate, survival without major morbidities, feed intolerance, necrotizing enterocolitis, duration of hospitalization and average daily weight gain. CONCLUSIONS: In neonates with birth weight 750-1250 g, early aggressive feeding regimen is feasible but not associated with significant reduction in all-cause mortality, culture positive sepsis or survival without major morbidities during hospital stay. Neonates with aggressive regimen have fewer days on IV fluids and reach full feed earlier.


Assuntos
Nutrição Enteral , Doenças do Prematuro , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Nutrição Enteral/efeitos adversos , Nutrição Enteral/métodos , Nutrição Enteral/mortalidade , Nutrição Enteral/estatística & dados numéricos , Enterocolite Necrosante , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Doenças do Prematuro/mortalidade , Doenças do Prematuro/terapia , Sepse
3.
J Matern Fetal Neonatal Med ; : 1-6, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30888887

RESUMO

OBJECTIVE: To evaluate the utility of superior mesenteric artery (SMA) flow velocity post feeding for predicting time to achieve full enteral feeds in very low birth weight (VLBW) neonates. SUBJECTS: In this prospective cohort study preterm VLBW infants were followed until they achieved full enteral feeding. RESULTS: There was no significant difference between prefeed and post feed SMA flow measurements in study subjects. At baseline, it was observed that Small for gestational age (SGA) babies had a significantly lower peak systolic velocity. Time-averaged mean velocity (TAMV) was significantly lower in SGA babies at baseline, 15, 30, 45, and 60 min post feed, but there were no within-group differences noted over time. CONCLUSION: SMA blood flow velocity measured pre-feed and post-feed times do not correlate with the time to achieve full enteral feeding in very low birth weight neonates. The clinical significance of lower Peak systolic velocity (PSV) and TAMV in SGA infants is unclear.

5.
Artigo em Inglês | MEDLINE | ID: mdl-26111571

RESUMO

Human milk fortification in preterm babies has become a standard of care in developed countries. Use of human milk fortifier (HMF) in very-low-birthweight infants is not a routine practice in India. There are concerns about high osmolality, feed intolerance, necrotizing enterocolitis, risk of contamination and added cost associated with use of HMF. There are limited data from India which address the issue of safety and short-term benefits of human milk fortification. This chapter highlights the issues related to human milk fortification in our country.


Assuntos
Alimentos Fortificados , Recém-Nascido de Baixo Peso/crescimento & desenvolvimento , Recém-Nascido Prematuro/crescimento & desenvolvimento , Leite Humano , Estatura , Custos e Análise de Custo , Enterocolite Necrosante/etiologia , Contaminação de Alimentos , Inocuidade dos Alimentos , Alimentos Fortificados/efeitos adversos , Alimentos Fortificados/economia , Idade Gestacional , Humanos , Índia , Terapia Intensiva Neonatal/métodos , Desnutrição/prevenção & controle , Leite Humano/química , Política Nutricional , Necessidades Nutricionais , Concentração Osmolar , Medição de Risco , Ganho de Peso
6.
Resuscitation ; 90: 21-4, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25636895

RESUMO

OBJECTIVE: To compare the duration of positive pressure ventilation (PPV) during delivery room resuscitation in neonates resuscitated with self-inflating bag (SIB) and T-piece resuscitator (TPR). DESIGN: Randomized control trial. SETTING: Delivery room and neonatal intensive care unit of a tertiary care center in northern India. PATIENTS: Consecutively born neonates more than 26 weeks of gestation requiring PPV at birth. INTERVENTION: Eligible neonates were randomized to two groups, SIB and TPR. OUTCOME MEASURES: Duration of PPV, intubation rates in delivery room, incidence of respiratory distress, need for mechanical ventilation during first 48h and its duration, need for surfactant replacement therapy and mortality during NICU stay. RESULTS: Fifty neonates received PPV with a SIB and 40 received PPV with a TPR. The mean (SD) birth weight and gestational age of neonates in SIB and TPR groups were 2264 (872) and 2065 (814)g; 35.1 (3.6) and 34.3 (3.7) weeks, respectively. The median (IQR) duration of PPV in delivery room was significantly less in TPR group as compared to SIB; 30 (30-60)s vs. 60 (30-90)s, respectively; (p<0.001). A higher proportion of neonates required delivery room intubation in SIB group as compared to TPR group (34% vs. 15%, p=0.04). In the TPR group, a higher proportion of neonates could be resuscitated with room air only (72.5% vs. 38%, p=0.001). Other outcomes were comparable in the two groups. Similar findings were observed in neonates <34 weeks, except that fewer neonates resuscitated with TPR required invasive ventilation (31.6% vs. 77.8%, p=0.008). CONCLUSION: Use of TPR during delivery room resuscitation resulted in shorter duration of PPV and lesser rates of intubation as compared to SIB. More infants in this group could be resuscitated with room air only (CTRI/2010/091/002946).


Assuntos
Salas de Parto , Respiração com Pressão Positiva/instrumentação , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Ressuscitação/instrumentação , Feminino , Humanos , Índia , Recém-Nascido , Intubação Intratraqueal/estatística & dados numéricos , Masculino , Respiração com Pressão Positiva/métodos , Ressuscitação/métodos , Fatores de Tempo
7.
J Pediatr Gastroenterol Nutr ; 60(2): 259-63, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25238118

RESUMO

BACKGROUND: The aim of the study was to compare prefeed abdominal circumference (AC) and gastric residual volume (GRV) as a measure of feed intolerance in very-low-birth-weight infants (VLBW). METHODS: Eighty VLBW infants were randomized to 2 groups; feed intolerance was monitored by measuring either GRV group or prefeed AC group. The primary outcome was time to full enteral feeds (180 mL · kg · day). Other main outcome measures were feed interruption days, duration of parenteral nutrition, incidence of culture positive sepsis, necrotizing enterocolitis, mortality, and duration of hospital stay. RESULTS: The median (interquartile range) time to achieve full feeds was 10 (9-13) versus 14 (12-17.5) days in AC and GRV groups, respectively (P < 0.001). Infants in AC group had fewer feed interruption days (0 [0-2] vs 2.0 [1, 5], P < 0.001) and shorter duration of parenteral nutrition (P < 0.001). The incidence of culture-positive sepsis in AC and GRV groups was 17.5% and 30 %, respectively (P = 0.18). Duration of hospital stay and mortality were comparable in both the groups. CONCLUSIONS: Prefeed AC as a measure of feed intolerance in VLBW infants may shorten the time taken to achieve full feeds.


Assuntos
Nutrição Enteral/métodos , Recém-Nascido de muito Baixo Peso , Nutrição Parenteral , Circunferência da Cintura , Enterocolite Necrosante/etiologia , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Recém-Nascido Prematuro , Tempo de Internação , Masculino , Nutrição Parenteral/efeitos adversos , Sepse/microbiologia , Sepse/mortalidade , Estômago , Fatores de Tempo , Resultado do Tratamento
8.
BMC Complement Altern Med ; 13: 158, 2013 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-24059266

RESUMO

BACKGROUND: In the present study, extracts prepared from the leaves of Rhus parviflora Roxb. (Anacardiaceae) were evaluated for their anti-HIV activity, which have been traditionally used for the treatment of neurological disorders such as anxiety, insomnia and epilepsy. METHODS: Aqueous and 50% ethanolic extracts prepared from leaves of the plant were tested for their cytotoxicity and anti-HIV property using reporter gene based assays as well as human peripheral blood lymphocytes (PBLs). Further these extracts were evaluated for their ability to inhibit HIV-1 reverse transcriptase (RT) and protease activity. Safety profile of the extracts was determined on viability of Lactobacillus sp., secretion of pro-inflammatory cytokines by vaginal keratinocytes and transepithelial resistance. RESULTS: Both aqueous (IC50 = 15 µg/ml) and 50% ethanolic (IC50 = 26 µg/ml) extracts prepared from leaves of R. parviflora showed anti-HIV activity in TZM-bl cells wherein the virus was treated with the extracts prior to infection. Further, both the extracts also inhibited virus load in HIV infected CEM-GFP cells and human PBLs. The anti-HIV activity is mediated through inhibition of HIV-1 protease activity. Both the extracts did not disturb the integrity of monolayer formed by intestinal epithelial Caco-2 cells. The extracts when tested up to 100 µg/ml did not significantly reduce the viability of L. plantarum, L. fermentum, L. rhamnosus and L. casei. The extracts (100 µg/ml) did not reveal any cytotoxic effect on vaginal keratinocytes (Vk2/E6E7). Levels of pro-inflammatory cytokines secreted by Vk2/E6E7 cells treated with both the plant extracts were within the non-inflammatory range. CONCLUSIONS: The studies reported herein showed in vitro anti-HIV activity and preliminary safety profile of the extracts prepared from the leaves of R. parviflora.


Assuntos
Infecções por HIV/virologia , Protease de HIV/metabolismo , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , Extratos Vegetais/farmacologia , Inibidores de Proteases/farmacologia , Rhus , Células CACO-2 , Feminino , HIV-1/enzimologia , Humanos , Extratos Vegetais/efeitos adversos , Folhas de Planta , Rhus/efeitos adversos
9.
Indian J Med Res ; 137(3): 540-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23640562

RESUMO

BACKGROUND & OBJECTIVES: Banaba (Lagerstroemia speciosa L.) extracts have been used as traditional medicines and are effective in controlling diabetes and obesity. The aim of this study was to evaluate the anti-HIV property of the extracts prepared from the leaves and stems of banaba, and further purification and characterization of the active components. METHODS: Aqueous and 50 per cent ethanolic extracts were prepared from leaves and stems of banaba and were evaluated for cytotoxicity and anti-HIV activity using in vitro reporter gene based assays. Further, three compounds were isolated from the 50 per cent ethanolic extract of banaba leaves using silica gel column chromatography and characterization done by HPLC, NMR and MS analysis. To delineate the mode of action of the active compounds, reverse transcriptase assay and protease assay were performed using commercially available kits. RESULTS: All the extracts showed a dose dependent inhibition of HIV-1-infection in TZM-bl and CEM-GFP cell lines with a maximum from the 50 per cent ethanolic extract from leaves (IC 50 = 1 to 25 µg/ml). This observation was confirmed by the virus load (p24) estimation in infected CEM-GFP cells when treated with the extracts. Gallic acid showed an inhibition in reverse transcriptase whereas ellagic acid inhibited the HIV-1 protease activity. INTERPRETATION & CONCLUSIONS: The present study shows a novel anti-HIV activity of banaba. The active components responsible for anti-HIV activity were gallic acid and ellagic acid, through inhibition of reverse transcriptase and HIV protease, respectively and hence could be regarded as promising candidates for the development of topical anti-HIV-1 agents.


Assuntos
Ácido Elágico/administração & dosagem , Ácido Gálico/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Linhagem Celular , Ácido Elágico/química , Inibidores Enzimáticos/administração & dosagem , Ácido Gálico/química , Infecções por HIV/enzimologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Protease de HIV/metabolismo , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/enzimologia , Humanos , Lagerstroemia/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/antagonistas & inibidores , Extratos Vegetais/química
10.
Indian Pediatr ; 50(1): 104-6, 2013 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-23396782

RESUMO

India has made impressive gains in its child survival indices during the past half a century with infant mortality rates declining from 159.3 in 1960 to 44 in 2011 and neonatal mortality rate declining from 47 (1990) to 32 (2010). Neonatal health is now an integral part of the countrys flagship program; National Rural Health Mission. Facility based newborn care is not only available in large public and private sectors hospitals, but also in about 300 of Indias district hospitals. Complementing these efforts is home based newborn care being delivered by community health volunteers. The last two decades has also witnessed an increase in newborn research and its incorporation into medical and paramedical education as a major course component. Neonatology now is an independent super-specialty in India. The National Neonatology Forum has had a major role in spearheading reforms in neonatal care in India.


Assuntos
Neonatologia/história , Neonatologia/tendências , Criança , História do Século XX , História do Século XXI , Humanos , Índia , Neonatologia/educação , Saúde da População Rural
11.
Virol J ; 10: 309, 2013 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-25228267

RESUMO

BACKGROUND: Acacia catechu (Mimosa family) stem bark extracts have been used traditionally as a dietary supplement as well as a folk medicine given its reported anti-inflammatory, immunomodulatory, hepatoprotective, antioxidant, anti-microbial and anti-tumor activities. The present study was undertaken to evaluate the anti-HIV-1 activity of the extracts from stem bark of A. catechu. METHODS: The aqueous and 50% ethanolic extracts of A. catechu stem bark were prepared and 50% ethanolic extract was further fractioned by successively partitioning with petroleum ether, chloroform and n-butanol. All the extracts and fractions were evaluated for cytotoxicity and anti-HIV-1 activity using different in vitro assays. The active n-butanol fraction was evaluated for its inhibition against HIV-1 reverse transcriptase, integrase, protease, pro-viral genome integration and viral Tat protein mediated transactivation. The effect of n-butanol fraction on the induction of pro-inflammatory cytokines secretion in Vk2/E6E7 cells and transepithelial resistance in Caco-2 and HEC-1A cells was investigated. RESULTS: The aqueous and 50% ethanolic extracts of A. catechu showed IC50 values of 1.8 ± 0.18 µg/ml and 3.6 ± 0.31 µg/ml, respectively in cell-free virus based assay using TZM-bl cells and HIV-1NL4.3 (X-4 tropic). In the above assay, n-butanol fraction exhibited anti-HIV-1 activity with an IC50 of 1.7 ± 0.12 µg/ml. The n-butanol fraction showed a dose-dependent inhibition against HIV-1NL4.3 infection of the peripheral blood lymphocytes and against HIV-1BaL(R-5-tropic) as well as two different primary viral isolates of HIV-1 infection of TZM-bl cells. The n-butanol fraction demonstrates a potent inhibitory activity against the viral protease (IC50 = 12.9 µg/ml), but not reverse transcriptase or integrase. Further, in Alu-PCR no effect on viral integration was observed. The n-butanol fraction interfered with the Tat-mediated Long Terminal Repeat transactivation in TZM-bl cells, mRNA quantitation (qRT-PCR) and electrophoretic mobility shift assay (EMSA). The n-butanol fraction did not cause an enhanced secretion of pro-inflammatory cytokines in Vk2/E6E7 cells. Additionally, no adverse effects were observed to the monolayer formed by the Caco-2 and HEC-1A epithelial cells. CONCLUSIONS: The results presented here show a potential anti-HIV-1 activity of A. catechu mediated by the inhibition of the functions of the viral protein and Tat.


Assuntos
Acacia/química , Antivirais/farmacologia , Inibidores da Protease de HIV/farmacologia , HIV-1/efeitos dos fármacos , Extratos Vegetais/farmacologia , Produtos do Gene tat do Vírus da Imunodeficiência Humana/antagonistas & inibidores , Antivirais/isolamento & purificação , Células Cultivadas , HIV-1/enzimologia , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Casca de Planta/química , Extratos Vegetais/isolamento & purificação , Caules de Planta/química
12.
Indian Pediatr ; 50(12): 1159-60, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24571019
13.
J Neonatal Surg ; 1(2): 21, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-26023380

RESUMO

Neural tube defect with its global involvement of nervous system has lot of implications. There is cotroversy in terms of timing of repair, simultaneous or metachronous ventriculoperitoneal shunt and criteria for shunt surgery in neonatal age. We are reporting our approach and results of management of this disease in neonatal period.

14.
Eur J Med Chem ; 46(4): 1181-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21339030

RESUMO

Novel oxindole derivatives bearing substituted cyclopropane ring have been designed on the basis of docking studies with HIV-1 RT using the software DS 2.5 and synthesized as probable NNRTIs against HIV-1 using rhodium(II) acetate-catalyzed stereoselective cyclopropanation reaction. The cyclopropane isomer, having trans relationship with respect to carbonyl of lactam moiety and functional group on the cyclopropane ring, was the major product in all cases along with a small amount of cis and methylene products. The trans isomers interacted well with HIV-1 RT through H-bonding with amino acids, like Lys101, Lys103, His235, Tyr318, constituting the non-nucleoside inhibitor binding pocket (NNIBP) during docking experiments. However, the compounds showed very little activity when subjected to in vitro anti-HIV-1 screening using ß-galactosidase assay (TZM-bl cells) and GFP quantification (CEM-GFP cells). The very low level of in vitro HIV inhibition, in comparison to predicted EC(50) values on the basis of computational studies, during CEM-GFP screening using AZT as positive control indicated that probably the HIV RT is not the viral target and the molecules work through some different mechanism.


Assuntos
Acetatos/química , Ciclopropanos/química , Ciclopropanos/farmacologia , HIV-1/efeitos dos fármacos , Indóis/química , Compostos Organometálicos/química , Ródio/química , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/toxicidade , Catálise , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclopropanos/síntese química , Ciclopropanos/toxicidade , Modelos Moleculares , Conformação Molecular , Oxindois , Estereoisomerismo , Relação Estrutura-Atividade , Especificidade por Substrato
15.
Indian Pediatr ; 47(10): 851-6, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20453269

RESUMO

OBJECTIVES: To evaluate the growth pattern of Very Low Birth Weight (VLBW) infants (birthweight <1500 g) during hospital stay and to compare the growth of Small for gestational age (SGA) and Appropriate for gestational age (AGA) infants. STUDY DESIGN: Prospective observational study. SETTING. Level III Neonatal Intensive Care Unit (NICU) in Northern India. PARTICIPANTS: A cohort of 97 VLBW infants, admitted to NICU at Sir Ganga Ram Hospital, from 1 January, 2007 to 31 July, 2008. INTERVENTION/MEASUREMENT: Weight, length and head circumference (HC) were serially measured from birth till discharge and respective Z scores were calculated as per data from Fentons references. Growth was also assessed by superimposing these trends on Ehrenkranzs postnatal growth charts. RESULTS: The mean Z scores for weight, length and HC at birth were -1.17, -1.09 and -0.54, respectively. These decreased to -2.16, -2.24 and -1.35, respectively by discharge. Both SGA and AGA infants exhibited a decrease of approximately 1 Z score in all parameters. On postnatal charts, growth of infants remained at or above respective reference lines, except in those below 1000 g at birth. Average daily weight gain after regaining birth weight was 15.18 ± 1.7 g/kg/d, whereas the increase in HC and length were 0.48 ± 0.2 cm/week and 0.60 ± 0.4 cm/week, respectively. These increments when compared to the intrauterine growth rates, indicated discrepant growth trends. CONCLUSIONS: VLBW infants suffered significant growth lag during NICU stay and exhibited disproportionately slow growth of HC and length.


Assuntos
Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Unidades de Terapia Intensiva Neonatal , Cefalometria , Nutrição Enteral , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Masculino , Ganho de Peso
16.
J Trace Elem Med Biol ; 20(3): 197-204, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16959597

RESUMO

Arsenic is a widespread environmental toxicant that may cause neuropathy, skin lesions, vascular lesions and cancer upon prolonged exposure. Improving nourishment like supplementation of micronutrients, antioxidants, vitamins and amino acids could be able to halve the risk in those who were previously the poor nourished. The present study was planned to investigate the preventive effects of zinc and n-acetylcysteine (NAC) supplementation either alone or in combination with arsenic on selected biochemical variables indicative of oxidative stress and liver injury in male rats. For 3 weeks 25 male wistar rats were exposed to arsenic as sodium arsenite (2 mg/kg, orally through gastric intubation) either alone or in combination with NAC (10 mg/kg, intraperitoneally), zinc (5 mg/kg, orally) or zinc plus NAC. Animals were sacrificed 24h after the last dosing for various biochemical parameters. Concomitant administration of zinc with arsenic showed remarkable protection against blood delta-aminolevulinic acid dehydratase (ALAD) activity as well as providing protection to hepatic biochemical variables indicative of oxidative stress (like thiobarbituric acid reactive substances (TBARS) level, catalase) and tissue injury. NAC supplementation on the other hand, was moderately effective in protecting animals from the toxic effects of arsenic. Interestingly, concomitant administration of zinc and NAC was most effective compared to zinc or NAC in eliciting above-mentioned protective effects. The above results suggest significant protective value of combined zinc and NAC administration in acute arsenic exposure.


Assuntos
Acetilcisteína/administração & dosagem , Arsênico/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Zinco/administração & dosagem , Administração Oral , Alanina Transaminase/sangue , Animais , Arsênico/antagonistas & inibidores , Arsênico/farmacocinética , Arsenitos/toxicidade , Aspartato Aminotransferases/sangue , Sinergismo Farmacológico , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Sintase do Porfobilinogênio/sangue , Ratos , Ratos Wistar , Compostos de Sódio/toxicidade , Distribuição Tecidual , Zinco/sangue
17.
Environ Toxicol Pharmacol ; 19(1): 131-8, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21783469

RESUMO

Administration of zinc either alone or in combination with monoisoamyl dimercaptosuccinic acid (DMSA) during and post-arsenic exposure was investigated in male mice. The animals were administered 2mgkg(-1) arsenic as sodium arsenite, intraperitoneally, once daily for 5 days either alone or in combination with 10mgkg(-1), zinc (as zinc acetate, orally), 50mgkg(-1) monoisoamyl dimercaptosuccinic acid (MiADMSA) given orally (p.o.), 2h after arsenic administration. Another group of arsenic treated animals was given both zinc (10mgkg(-1)) and MiADMSA (50mgkg(-1), p.o.). Animals were sacrificed 24h after the last dose. In another set of experimentation, arsenic pre-exposed mice (2mgkg(-1), i.p. for 5 days) were treated with saline, zinc, MiADMSA or zinc plus MiADMSA for next 3 days and sacrificed thereafter. Exposure to arsenic led to a significant inhibition of blood δ-aminolevulinic acid dehydratase (ALAD), depletion of glutathione (GSH) level and marginal elevations of zinc protoporphyrin (ZPP). Arsenic exposure caused a significant decrease in hepatic and renal GSH level and an increase in liver oxidized glutathione (GSSG) and liver and kidney thiobarbituric acid reactive substance (TBARS) levels. Concomitant administration of zinc with arsenic provided significant protection to blood ALAD activity while, GSH and ZPP levels remained unaltered. Co-administration of MiADMSA with arsenic significantly prevented accumulation of arsenic in blood, liver and kidney while, zinc had no effect on tissue arsenic concentration. Combined administration of zinc and MiADMSA had no major additional beneficial effects over their individual effects. Interestingly, post-arsenic exposure treatment with MiADMSA provided significant recovery in blood ALAD activity while, zinc supplementation alone had no effect. The best results however, were obtained when MiADMSA was administered along-with zinc. Most of the biochemical variables indicative of hepatic oxidative stress responded favorably to MiADMSA treatment while, zinc administration had no effect. Administration of MiADMSA significantly depleted arsenic concentration from the soft tissues while, combined zinc and MiADMSA had no additional beneficial effect over the individual effect of MiADMSA. The results thus lead us to conclude that in order to achieve best effects of chelation therapy, co-administration of zinc with chelator might be preferred. However, detailed experimental studies with variable doses and after chronic arsenic exposure are required.

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