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1.
Cancer Epidemiol ; 88: 102514, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38141472

RESUMO

OBJECTIVES: Advanced stage is linked to prolonged patient and diagnostic interval for gastrointestinal (GI) cancers. However, objective evidence of this fact is not so forthcoming. Our aim was to study the effect of these intervals on the risk of advanced stage for GI cancers. METHODS: We performed this retrospective cohort study to analyse the effect of patient and diagnostic intervals on final stage in seven types of GI cancers, during 2013 and 2022. Two groups of stage: early (TNM- 0, I, II) and advanced (TNM- III, IV), were formed. Outcome studied was interdependence between patient and diagnostic intervals and incidence of advanced stage. Binary logistic regression was applied to calculate odds ratio of having an advanced versus early stage as a function of duration of these delays, in the whole cohort. We used restricted cubic splines with five knots to study flexible and non-monotonic pattern of association between these delays and stage. RESULTS: In whole cohort of 1859 patients, median patient and diagnostic intervals of early and advanced cancers were 21 and 26 days and 120 and 45 days, respectively. There was a positive association between patient interval and advanced stage (odds ratio [OR], 1.04, confidence interval [CI], 1.035 to 1.045; P < 0.001) and negative association between diagnostic interval and advanced stage (odds ratio, 0.98, CI, 0.976 to 0.998; P-0.017), among all gastrointestinal cancers combined. Increased risk of advanced stage started from day one of patient interval and for diagnostic interval there was an initial decrease followed by subsequent increase in the risk of advanced stage beyond 26 days of diagnostic interval. CONCLUSIONS: Longer patient and diagnostic intervals increase the risk of advanced stage in gastrointestinal cancers.


Assuntos
Detecção Precoce de Câncer , Neoplasias Gastrointestinais , Humanos , Estudos Retrospectivos , Diagnóstico Tardio , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Modelos Logísticos
3.
Indian Pediatr ; 60(5): 364-368, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36756997

RESUMO

OBJECTIVE: To study the correlation of objective parameters for diagnosing shock viz., perfusion index (PI), plethysmography variability index (PVI) and serum lactate (SL) with invasive blood pressure in late preterm and term infants with shock. METHODS: Prospective observational study (diagnostic test) conducted at the neonatal intensive care unit of Kanchi Kamakoti CHILDS Trust Hospital, Chennai between June, 2018 and May, 2020. Term and late preterm neonates with shock were included in the study. PI, PVI, SL, SpO2 and heart rate were monitored. PI, PVI and SLL were recorded at 0,12, 24 and 72 hours of onset of shock. All the babies were followed up till discharge or death. RESULTS: Total 78 neonates were enrolled in the study. At 0 hour, SL and PVI had negative correlation (P =0.002 and P=0.003) while PI had a weak-to-moderate positive correlation (P=0.002) with invasive blood pressure. SL ≥4.65 had a sensitivity of 75% and specificity of 75.8%, and PI <0.455 had a sensitivity of 65%, and specificity of 58.6% for predicting invasive hypotension. PVI ≥23.5 had a sensitivity of 90% and specificity of 63.8% in predicting invasive hypotension. CONCLUSION: PI has moderate positive correlation while SL and PVI have moderate negative correlation with invasive blood pressure. The cutoff values of SL ≥4.65, PI <0.45 and PVI ≥23.5 can predict invasive hypotension with good sensitivity and negative predictive value.


Assuntos
Hipotensão , Choque , Recém-Nascido , Criança , Humanos , Lactente , Pressão Sanguínea , Índice de Perfusão , Índia/epidemiologia , Choque/diagnóstico , Pletismografia , Lactatos
4.
Theor Appl Genet ; 135(12): 4549-4563, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36271945

RESUMO

KEY MESSAGE: A key genomic region was identified for resistance to FSR at 168 Mb on chromosome 6 in GWAS and haplotype regression analysis, which was validated by QTL mapping in two populations. Fusarium stalk rot (FSR) of maize is an economically important post-flowering stalk rot (PFSR) disease caused by Fusarium verticillioides. The pathogen invades the plant individually, or in combination with other stalk rot pathogens or secondary colonizers, thereby making it difficult to make accurate selection for resistance. For identification and validation of genomic regions associated with FSR resistance, a genome-wide association study (GWAS) was conducted with 342 maize lines. The panel was screened for FSR in three environments using standard artificial inoculation methodology. GWAS using the mixed linear model corrected for population structure and kinship was done, in which 290,626 SNPs from genotyping-by-sequencing were used. A total of 7 SNPs, five on chromosome 6 showing strong LD at 168 Mb, were identified to be associated with FSR. Haplotype regression analysis identified 32 haplotypes with a significant effect on the trait. In a QTL mapping experiment in two populations for validating the identified variants, QTLs were identified with confidence intervals having overlapped physical coordinates in both the populations on chromosome 6, which was closely located to the GWAS-identified variants on chromosome 6. It makes this genomic region a crucial one to further investigate the possibility of developing trait markers for deployment in breeding pipelines. It was noted that previously reported QTLs for other stalk rots in maize mapped within the same physical intervals of several haplotypes identified for FSR resistance in this study. The possibility of QTLs controlling broad-spectrum resistance for PFSR in general requires further investigation.


Assuntos
Fusarium , Humanos , Zea mays/genética , Resistência à Doença/genética , Estudo de Associação Genômica Ampla , Cromossomos Humanos Par 6 , Doenças das Plantas/genética , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único
5.
J Infect Public Health ; 15(3): 321-323, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35144047

RESUMO

The biggest public health catastrophe of this century-the SARS coronavirus-2, 2019 (COVID-19) pandemic has affected nearly all countries. Countries after countries were gripped by the intermittent waves of the infection. One of the most affected countries was India, wherein the second wave of the pandemic afflicted the vast swathe of the nation. The medical community was overwhelmed and stressed with the inordinate number of patients. Doctors were inundated with the task of managing all kinds of COVID-19 patients ranging from mildly symptomatic to critically ill, in addition to the non-COVID-19 patients. The life of most of the population was significantly disrupted due to the fear of infection and lockdowns in various places. Due to multiple reasons, physician access was limited for mild to moderately sick patients. During this time, online consultations were at their peak and many groups came forward to help Indian patients. These groups were supported largely by Indian doctors based overseas.


Assuntos
COVID-19 , Controle de Doenças Transmissíveis , Humanos , Índia/epidemiologia , Pandemias/prevenção & controle , SARS-CoV-2
6.
Anim Biotechnol ; 33(6): 1045-1055, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33427028

RESUMO

The current study is the first worldwide to assess the genetic diversity of Kadaknath poultry using amplified fragment length polymorphism (AFLP) markers. Out of total 96 accessions, four were outliers and 92 were Kadaknath accessions of which 30 were males, 62 were females. Of these, 74 were jet black, 7 penciled and 11 were golden feather color type of Kadaknath. High level of polymorphism (23.94%) was observed in 387 loci amplified using six AFLP primer combinations. The Jaccard's similarity coefficient ranged from 0.211 to 0.754 with an average dissimilarity of 0.517. Based on the neighbor-joining method of clustering, all accessions were clustered into seven major clusters which were not consistent with their respective geographical locations. The mean values of effective multiplex ratio, polymorphic information content, resolving power and marker index were 15.16, 0.38, 9.87 and 5.85 respectively. Further, the high log-likelihood score was produced when the number of populations (K) was set at 7 while carrying out the population STRUCTURE analysis, which was also congruent with clustering analysis based on genetic diversity. The extent of genetic diversity detected in this study could be used for germplasm selection and developing conservation strategies of pure breed of Kadaknath.


Assuntos
Polimorfismo Genético , Aves Domésticas , Animais , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Aves Domésticas/genética , Análise por Conglomerados , Índia , Variação Genética/genética
8.
Indian Pediatr ; 58(10): 928-931, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33864450

RESUMO

OBJECTIVE: To evaluate the prognostic value of amplitude-integrated EEG in term neonates with encephalopathy. METHODS: In this prospective observational study we enrolled 58 term neonates with encephalopathy from March, 2019 to March, 2020. Level of alertness was ascertained as per Volpe's classification and tone as per Amiel-Tison scale of tone assessment. Abnormal aEEG was defined as background activity other than continuous normal voltage, or immature or absent sleep-wake cycle, or presence of electrical seizure. Primary outcome was abnormal neurological examination at discharge and/or death prior to discharge. RESULTS: Out of 58 neonates, aEEG was abnormal for 50 (86.2%). There was a statistically significant association between abnormal aEEG findings and primary outcome (P=0.04). The aEEG score cut-off of >2 had satisfactory sensitivity (88.8%) and specificity (79.5%) to predict primary outcome. CONCLUSIONS: Abnormal aEEG had good sensitivity but low specificity to predict the primary outcome in term neonates with encephalopathy.


Assuntos
Encefalopatias , Eletroencefalografia , Encefalopatias/diagnóstico , Humanos , Recém-Nascido , Valor Preditivo dos Testes , Prognóstico , Sensibilidade e Especificidade
9.
Plant Physiol Biochem ; 159: 53-66, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33338820

RESUMO

We report a novel chitosan-silicon nanofertilizer (CS-Si NF) wherein chitosan-tripolyphosphate (TPP) nano-matrix has been used to encapsulate silicon (Si) for its slow release. It was synthesied by ionic gelation method and characterized by dynamic light scattering (DLS), fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and atomic absorption spectrophotometry (AAS). The developed CS-Si NF exhibited slow release of Si and promoted gowth and yield in maize crop. Seeds primed with different concentrations of CS-Si NF (0.04-0.12%, w/v) exhibited up to 3.7 fold increased seedling vigour index (SVI) as compared with SiO2. Its foliar spray significantly induced antioxidant-defence enzymes' activities and equilibrated cellular redox homeostasis by balancing O2-1 and H2O2 content in leaf as compared with SiO2. Application of nanofertilizer (0.01-0.16%, w/v) stirred total chlorophyll content (21.01-25.11 mg/g) and leaf area (159.34-166.96 cm2) to expedite photosynthesis as compared with SiO2. In field experiment, 0.08% CS-Si NF resulted in 43.4% higher yield/plot and 0.04% concentration gave 45% higher test weight as compared with SiO2. Fecund and myriad effects of developed nanofertilizer over SiO2 could be attributed to slow/protective release of Si from nanofertilizer. Overall, results decipher the enormous potential of CS-Si NF for its use as a next generation nanofertilizer for sustainable agriculture.


Assuntos
Agricultura , Quitosana , Dióxido de Silício , Zea mays , Agricultura/métodos , Quitosana/farmacologia , Fertilizantes/normas , Peróxido de Hidrogênio/metabolismo , Dióxido de Silício/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Zea mays/efeitos dos fármacos
10.
Environ Sci Pollut Res Int ; 28(4): 3960-3971, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33170464

RESUMO

Diesel engines are playing a vital responsibility in the field of automobile, agriculture, construction, and power generation. In the present world, much research is going on in the field of renewable energy to replace conventional sources of energy. But it is not very easy to replace diesel engines with other sources due to the better power output and reliability. The emissions from CI engines are very harmful for human health and for the environment. The major emissions are smoke and NOx which need to be controlled in an effective manner. In this work, direct injection variable compression ratio CI engine was used in experimental investigations for determining the combustion characteristics for D-MXEE-NM blends at different compression ratios. By performance analysis and exhaust emission of engine at peak load, D-MXEE5-NM2.5 (diesel 92.5%, 2-methoxyethyl ether 5%, and nitromethane 2.5%) blend was identified as best blend among all tested fuel blends and pure diesel at normal compression ratio (17.5). Further, all considered fuels with different CR values at peak load were ranked by Entropy-VIKOR method. From the analysis, D-MXEE5-NM2.5 at CR 19.5 was found as best fuel blend (ranked first) among all fuel blends and different compression ratios considered with same experimental conditions. By comparison of best fuel blend D-MXEE5-NM2.5 (at advanced compression ratio 19.5) with diesel (at standard CR 17.5), emission decline (HC 66.66%, CO 70.00%, and smoke 16.09%) and performance improvement (decrement in BSFC 7.07% and increment in BTE 4.41%) were obtained significantly at peak load. However, negligible increment in NOx (3.58%) was observed.


Assuntos
Gasolina , Óxidos de Nitrogênio , Biocombustíveis , Monóxido de Carbono/análise , Éter , Éteres , Humanos , Metano/análogos & derivados , Óxidos de Nitrogênio/análise , Nitroparafinas , Reprodutibilidade dos Testes , Emissões de Veículos
11.
Nutrients ; 11(5)2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31117218

RESUMO

Psyllium and lactitol have been reported to increase fecal volume, moisture content and bowel movement frequency (BMF). However, the benefits of their combined use on constipation has not been examined. The aim of this study was to evaluate the effects of a 4-week intervention with lactitol and/or psyllium on bowel function in constipated volunteers. Adults (N = 172) who were diagnosed with functional constipation per Rome III criteria were randomized to four treatment groups: 10 g lactitol, 3.5 g psyllium, a combination of 10 g lactitol and 3.5 g psyllium, or placebo. The primary endpoint was change in BMF from Day 0 to 28 as compared to placebo. Secondary endpoints were assessed by inventories, including stool consistency, patient assessment of constipation symptoms and quality of life, relief of constipation, 24-h food recall, physical activity, product satisfaction and adverse events (AE). BMF increased by 3.0 BMs with lactitol, by 2.9 with psyllium, and by 3.1 with the combination, but was not different from placebo (3.7 BMs). Other clinical endpoints were similar between treatments. No serious AEs were reported. In conclusion, this study showed a similar effect on relief of constipation in all treatment groups. The treatments that were administered to the volunteers were well tolerated.


Assuntos
Constipação Intestinal/tratamento farmacológico , Psyllium/uso terapêutico , Álcoois Açúcares/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Psyllium/administração & dosagem , Álcoois Açúcares/administração & dosagem
12.
Indian Pediatr ; 54(6): 507-508, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28667727

RESUMO

We prospectively analyzed the coagulation abnormalities in 111 children with Celiac disease at diagnosis and its association with histology grade on duodenal biopsy; 27% had deranged prothrombin time. There was an increasing proportion of coagulopathy with progression of Marsh Grade on duodenal histology.


Assuntos
Transtornos da Coagulação Sanguínea , Doença Celíaca/complicações , Doença Celíaca/epidemiologia , Adolescente , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Índia/epidemiologia , Lactente , Coeficiente Internacional Normatizado , Masculino , Estudos Prospectivos
13.
Physiol Mol Biol Plants ; 22(2): 193-205, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27436911

RESUMO

Phenotypic variation of important seed traits like seed length, seed breadth, seed thickness, 100 seed weight and seed oil content were recorded in a total of 157 collected accessions of Pongamia. Out of these, fatty acid profiles of 38 accessions selected based on their high and low oil content was analyzed. Fatty acid profile revealed high variability in stearic, oleic and linoleic acid which varied from 0.42 to 10.61 %, 34.34 to 74.58 %, and 7.00 to 31.28 % respectively. Variations in palmitic and linolenic acid were small. Iodine value, saponification number and cetane number (CN) of fatty acid methyl esters (FAME) of seed oil ranges from 186.99 to 201.25, 81.13 to 108.19 and 46.16 to 56.47 respectively. Fatty acid compositions, degree of unsaturation and CN are the important parameters, which are used to determine quality of FAME were used as biodiesel. Some of the Pongamia accessions identified were higher in oil content while some accessions showed higher degree of unsaturation and a few of them had CN values higher than 55. Genetic diversity analysis with six TE-AFLP primers generated a total of 334 bands out of which 174 (52.10 %) were polymorphic. The genetic similarity ranged from 0.11 to 0.47. These findings clearly showed high level of genetic diversity and all economically desirable traits were not present in a single genotype of Pongamia. All these traits could be selected from these CPTs and transfer to a single elite variety through selection and breeding programme and could be utilized for large scale multiplication and plantation to produce high quantity and quality biodiesel in future.

14.
Indian J Gastroenterol ; 34(6): 442-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26743101

RESUMO

BACKGROUND: Magnetic resonance cholangiopancreatography/magnetic resonance splenoportovenography (MRCP/MRSPV) is now the investigation of choice for the diagnosis of portal cavernoma cholangiopathy (PCC). Endoscopic ultrasound (EUS) is an emerging diagnostic modality for the diagnosis of PCC and may be better than MRCP/MRSPV to see the layer-wise localization of varices and to differentiate between varices, stone, and malignancy. METHODS: Retrospective data of 50 patients of extrahepatic portal vein obstruction (EHPVO) were collected, and comparison between MRCP/MRSPV and EUS was done for the diagnosis of PCC. RESULTS: Out of 50 patients, 56 % (28) were males, 44 % (22) females, and 24 % (12) symptomatic. Biliary changes were seen in 40 patients (80 %). Epicholedochal collateral (EPEC) was detected in 48 % and 20 % in MRCP/MRSPV and EUS, respectively. Perforators (PER) and intracholedochal collateral (ICC) were better seen with EUS (72 % and 48 %) as compared to MRCP/MRSPV (0 % and 8 %), and p-values were significant (<0.05). EUS has a sensitivity of 33.33 % and a specificity of 92.31 % for EPEC. Portal cavernoma (PC) and collateral at porta (CP), paracholedochal collateral (PAC), perisplenic (PS) and peripancreatic collateral (PPC), pericholedochal collateral (PEC), intrahepatic biliary radical dilatation (IHBRD), perigallbladder collateral (PG), common bile duct dilatation (CBDD) and common hepatic duct dilatation (CHDD), common bile duct stricture (CBDS), and retropancreatic collateral (RPC) were comparable between the two modalities. CONCLUSIONS: EUS detected PER and ICC better than MRCP/MRSPV, while MRCP/MRSPV was more sensitive for detecting EPEC.


Assuntos
Doenças dos Ductos Biliares/diagnóstico , Ductos Biliares Extra-Hepáticos , Colangiopancreatografia por Ressonância Magnética , Endossonografia , Hipertensão Portal/diagnóstico , Imageamento por Ressonância Magnética , Veia Porta/anormalidades , Portografia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
16.
Indian J Gastroenterol ; 33(3): 237-40, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24307494

RESUMO

BACKGROUND AND STUDY AIM: Short-term common bile duct stenting has been shown to decrease stone size, but its effect on mechanical lithotripsy has not been reported. PATIENTS AND METHODS: Sixty patients of difficult bile duct stones were subjected to mechanical lithotripsy. Thirty patients were subjected to mechanical lithotripsy at the time of first endoscopic retrograde cholangiopancreatography (group A) while another 30 patients were subjected to mechanical lithotripsy using trapezoid basket after a short period of stenting (group B). The effect on the hardness of stone, durability of the basket after stenting, and duration of mechanical lithotripsy was studied. RESULTS: Lithotripsy after stenting was less time consuming, and durability of the basket was much more in comparison to lithotripsy without stenting (p < 0.001). Friability of stone increased after stenting, and it was easy to break the stone after preliminary stenting. CONCLUSION: Short-term (2 to 3 months) stenting should be done in all the patients with large stones before subjecting them to mechanical lithotripsy to make the procedure less time consuming and more convenient to endoscopist.


Assuntos
Coledocolitíase/cirurgia , Ducto Colédoco/cirurgia , Litotripsia/métodos , Stents , Adulto , Colangiopancreatografia Retrógrada Endoscópica , Coledocolitíase/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
17.
Endosc Ultrasound ; 2(4): 204-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24949397

RESUMO

OBJECTIVE: Asymptomatic dilatation of bile duct and symptomatic sphincter of Oddi dysfunction have been reported in opium addicts. Except one case report, there is no report in the literature on endoscopic ultrasound (EUS) study of pancreato-biliary system in opium addicts. The aim of the present study was to report the EUS features of pancreato-biliary system in opium addicts presenting with abdominal pain. PATIENTS AND METHODS: A total of 15 opium addicts presenting with upper abdominal pain and dilated common bile duct (CBD) and or pancreatic duct (PD) on abdominal ultrasound were included in this study. EUS findings of pancreato-biliary system were analyzed in these patients. RESULTS: All the 15 patients were males (mean age 53.3 years) presented with upper abdominal pain. Mean duration of opium addiction was 20.1 years. On EUS CBD was dilated in all the patients while PD was dilated in six patients. Gall bladder, liver and pancreatic parenchyma was normal in all these patients. Surface area of papilla of Vater (SPV) was increased in 12 patients. CONCLUSION: Opium addiction causes obstruction at ampulla and produces dilatation of bile duct and PD. Bile duct dilatation was seen in all the patients while PD dilatation was seen in few patients. Increase in SPV was a peculiar finding and appears to be as a result of direct effect of opium on ampulla.

18.
Indian J Exp Biol ; 48(3): 314-7, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21046987

RESUMO

Hexane, chloroform and ethyl acetate extracts (100 microg/ml) of Alpinia galanga rhizomes exhibited significant activity in vitro against promastigotes of L. donovani. Twelve compounds namely, methyleugenol (1), p-coumaryl diacetate (2), 1'-acetoxychavicol acetate (3), 1'-acetoxyeugenol acetate (4), trans-p-acetoxycinnamyl alcohol (5), trans-3,4-dimethoxycinnamyl alcohol (6), p-hydroxybenzaldehyde (7), p-hydroxycinnamaldehyde (8), trans-p-coumaryl alcohol (9), galangin (10), trans-p-coumaric acid (11) and galanganol B (12) were isolated from these extracts. Of these, compounds 2, 3, 4 and 5 were found most active in vitro against promastigotes of L. donovani with IC50 values of 39.3, 32.9, 18.9 and 79.9 microM respectively. This is the first report of antileishmanial activity of the extracts and isolated constituents of A. galanga.


Assuntos
Alpinia/química , Antiprotozoários/farmacologia , Leishmania donovani/efeitos dos fármacos , Extratos Vegetais/farmacologia , Acetatos/química , Animais , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Clorofórmio/química , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Relação Dose-Resposta a Droga , Eugenol/análogos & derivados , Eugenol/química , Eugenol/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Hexanos/química , Leishmania donovani/crescimento & desenvolvimento , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Propionatos , Rizoma/química
19.
Eur J Med Chem ; 45(8): 3439-45, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20546981

RESUMO

Based on reported antileishmanial activity of naturally occurring alkaloid piperine and amino acid esters, their conjugates were synthesized by the hydrolysis of piperine to piperic acid followed by reaction with amino acid methyl esters. These conjugates were further converted to compounds with free carboxyl group and those with reduced double bonds. The synthesized compounds were evaluated for activity against promastigote and amastigote forms of L. donovani in vitro. All the compounds showed better activity than either piperine or the amino acid methyl esters. Piperoyl-valine methyl ester was the most active compound showing an IC50 of 0.075 mM against the amastigotes. Two active compounds were evaluated for in vivo activity in golden hamster model of leishmaniasis.


Assuntos
Alcaloides/química , Aminoácidos/síntese química , Aminoácidos/farmacologia , Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Benzodioxóis/química , Leishmania donovani/efeitos dos fármacos , Piperidinas/química , Alcamidas Poli-Insaturadas/química , Aminoácidos/química , Aminoácidos/toxicidade , Animais , Antiprotozoários/química , Antiprotozoários/uso terapêutico , Domínio Catalítico , Cricetinae , Ésteres/química , Humanos , Concentração Inibidora 50 , Leishmaniose/tratamento farmacológico , Masculino , Modelos Moleculares
20.
Br J Pharmacol ; 142(5): 899-911, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15197101

RESUMO

Free radicals have been implicated in cerebral ischemia reperfusion (IR) injury. Massive production of nitric oxide and superoxide results in continuous formation of peroxynitrite even several hours after IR insult. This can produce DNA strand nicks, hydroxylation and/or nitration of cytosolic components of neuron, leading to neuronal death. Peroxynitrite decomposition catalysts 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron (III) (FeTMPyP) and 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III) (FeTPPS) have been demonstrated to protect neurons in in vitro cultures; however, their neuroprotective efficacy in cerebral IR injury has not been explored. In the present study, we investigated the efficacy and the therapeutic time window of FeTMPyP and FeTPPS in focal cerebral ischemia (FCI). FCI was induced according to the middle cerebral artery occlusion (MCAO) method. After 2 h of MCAO and 70 h of reperfusion, the extent of neurological deficits, infarct and edema volume were measured in Sprague-Dawley rats. FeTMPyP and FeTPPS were administered at different time points 2, 6, 9 and 12 h post MCAO. FeTMPyP and FeTPPS (3 mg kg(-1), i.v.) treatment at 2 and 6 h post MCAO produced significant reduction in infarct volume, edema volume and neurological deficits. However, treatment at latter time points did not produce significant neuroprotection. Significant reduction of peroxynitrite in blood and nitrotyrosine in brain sections was observed on FeTMPyP and FeTPPS treatment. As delayed treatment of FeTMPyP and FeTPPS produced neuroprotection, we tested whether treatment had any influence over the apoptotic neuronal death. DNA fragmentation and in situ nick end-labeling assays showed that FeTMPyP and FeTPPS treatment reduced IR injury-induced DNA fragmentation. In conclusion, peroxynitrite decomposition catalysts (FeTMPyP and FeTPPS) produced prominent neuroprotection even if administered 6 h post MCAO and the neuroprotective effect is at least in part due to the reduction of peroxynitrite and apoptosis.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Metaloporfirinas/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Ácido Peroxinitroso/metabolismo , Animais , Apoptose/efeitos dos fármacos , Encéfalo/patologia , Edema Encefálico/patologia , Isquemia Encefálica/patologia , Catálise , Fragmentação do DNA/efeitos dos fármacos , Imunofluorescência , Marcação In Situ das Extremidades Cortadas , Infarto da Artéria Cerebral Média/patologia , Cinética , Masculino , Microscopia Eletrônica , Artéria Cerebral Média/fisiologia , Doenças do Sistema Nervoso/psicologia , Ratos , Ratos Sprague-Dawley , Tirosina/metabolismo
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