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1.
J Chromatogr Sci ; 60(2): 117-125, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33948642

RESUMO

This work describes the highly selective and sensitive robust analytical method (gas chromatography) for the qualitative and quantitative analysis of commonly used residual solvents (like methanol, ethanol, acetonitrile, dichloromethane, methyl tert-butyl ether, n-hexane, 1-propanol, ethyl acetate, tetrahydrofuran, N,N-diisopropylethylamine (DIPEA) and dimethylformamide), in an active pharmaceuticals ingredients. The developed method was optimized with good resolution (>1.9 between close eluting solvents) and a shorter run time (20 min). All the solvents were separated using GC column DB-624, 30-m length, 0.32-mm diameter, 1.8-µm particle size, nitrogen as a carrier gas and recorded the signals using flame ionization detector (FID). Further, analytical method validation has been performed for the developed analytical method and the validation results demonstrated its routine application for the determination of residual solvents content by GC-head space (HS). The practical application was demonstrated by the suitable API batch analysis (having sample Con. 40 mg/mL). The present developed method has more advantages than the other methods for the qualitative and quantitative applications, such as shorter runtime, selective for multiple solvents (11 organic solvents) analysis at a time, highly sensitive at ppm levels. This GC-HS method could be used for the qualitative and quantitative determination of the residual solvents content in APIs.


Assuntos
Metanol , Preparações Farmacêuticas , Cromatografia Gasosa/métodos , Ionização de Chama , Solventes/análise
2.
J Postgrad Med ; 58(4): 255-61, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23298919

RESUMO

BACKGROUND: Increasing prevalence of hypertension is a public health problem in India. AIMS: To study prevalence, correlates, and awareness of hypertension among tribal adult population in Kerala. SETTING AND DESIGN: A community-based, cross-sectional study was carried out in tribal areas of Kerala by adopting multistage random sampling procedure. MATERIALS AND METHODS: Data was collected on socio-demographic and behavioral factors, and anthropometric measurements were carried out. Body mass index (BMI) was categorized using the classification recommended for Asians. Waist circumference ≥ 90 cm for men and ≥ 80 cm for women was used cut off for defining an abdominal obesity. Bivariate and multivariate analysis was carried out to study association of hypertension with socio-demographic variables, personal habits, and obesity. RESULTS: A total of 4,193 adults (men 1,891, women: 2,302) of ≥ 20 years of age were covered. The overall prevalence of hypertension was 40% (n=1671). The prevalence of hypertension increases with increase in age among both the genders. Regression analysis showed that the risk of hypertension was significantly (P<0.001) lower among educated and among higher socio-economic status group. Sedentary activity had 1.3 times (CI=1.09-1.60) and alcohol consumption had 1.4 (CI=1.17-1.73) times higher risk of hypertension. The risk of hypertension was 1.7 times higher among overweight/obese subjects. Overall, only 10% (n=164) of the adult population was aware of hypertension status, and about 8% (n=129) were on regular treatment. CONCLUSION: It was observed that the prevalence of hypertension was higher among tribal adult population of Kerala and was associated with age, gender, education, HHs wealth index, physical inactivity, alcohol consumption, and overweight/obesity.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Hipertensão/etnologia , Obesidade/etnologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Índice de Massa Corporal , Pesquisa Participativa Baseada na Comunidade , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Hipertensão/complicações , Índia/etnologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Vigilância da População , Análise de Regressão , Fatores de Risco , Distribuição por Sexo , Fatores Socioeconômicos , Circunferência da Cintura , Adulto Jovem
3.
J Pharm Biomed Anal ; 56(3): 484-90, 2011 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-21782369

RESUMO

In the impurity profile of naproxen around 0.6% unknown polar impurity was detected by high performance liquid chromatography (HPLC). The product ion spectrum of the impurity and Naproxen was recorded in LCMS/MS and the fragmentation pattern of the impurity was observed to be similar to the fragmentation pattern of Naproxen with only a difference of two atomic mass units. The high resolution mass spectrum (HRMS) of the impurity displayed a protonated molecular ion at m/z 229.0863, which corresponds to the pseudomolecular formula C(14)H(13)O(3)(+). Based on LC/MS/MS, HRMS, 1D and 2D NMR data, the structure of the impurity was characterized as 2-(6-methoxynaphthalen-2-yl)acrylic acid. The acrylic acid impurity was synthesized in the laboratory and co injected in HPLC to confirm the retention time. RRF of the impurity was determined by (1)H NMR method and also by conventional HPLC slope method and the RRF values are found to be 6.11 and 5.64, respectively. The values are comparable and (1)H NMR method of RRF determination is complimentary and can be effectively used as an alternative method to conventional HPLC method especially in early stages of development when availability of impurity standards is not possible.


Assuntos
Acrilatos/análise , Contaminação de Medicamentos , Naproxeno/análise , Acrilatos/química , Cromatografia Líquida de Alta Pressão/métodos , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Naproxeno/química
4.
J Pharm Biomed Anal ; 46(4): 780-3, 2008 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-18178357

RESUMO

A gas chromatography-mass spectrometry (GC-MS) method has been developed for the identification and determination of two carcinogenic and genotoxic mesylate esters viz. methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) in imatinib mesylate (INM). The method was optimized based on the peak shapes and resolution of MMS and EMS. The method was validated as per International Conference of Harmonization (ICH) guidelines in terms of limits of detection (LOD), limit of quantitation (LOQ), linearity, precision, accuracy, specificity and robustness. The LOD and LOQ values were found to be 0.3 and 1.0 microg/ml, respectively. The method is linear within the range of 1-15 microg/ml for both the compounds. These mesylate esters were not found in three different batches of pure and pharmaceutical formulations of INM.


Assuntos
Metanossulfonato de Etila/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metanossulfonato de Metila/análise , Piperazinas/análise , Pirimidinas/análise , Benzamidas , Contaminação de Medicamentos , Mesilato de Imatinib
5.
Reprod Fertil Dev ; 19(5): 612-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17601408

RESUMO

The efficiency of laparoscopic ovum pick-up (LOPU) followed by in vitro embryo production (IVEP) in the propagation of aged goats with poor reproductive performance was evaluated in the present study. Follicular development was stimulated in donor goats with 80 mg follicle-stimulating hormone and 300 IU equine chorionic gonadotrophin administered 36 h before LOPU. In addition, goats were heat synchronised with intravaginal sponges containing 60 mg medroxyprogesterone acetate for 10 days and a luteolytic injection of 125 microg cloprostenol 36 h before sponge removal and LOPU. Following in vitro maturation (IVM), oocytes were fertilised in vitro with frozen-thawed semen produced using the egg yolk-free Bioxcell extender (IVM, L'Aigle, France). The average number of follicles aspirated (17.9 +/- 8.0 per goat), oocytes recovered (15.7 +/- 8.4 per goat) and cleavage after IVM/in vitro fertilisation followed by a short 24-h in vitro culture in modified synthetic oviduct fluid medium (72 +/- 7%) were similar to results reported previously by our group and others in younger goats. A total of 296 embryos was transferred into 50 heat-synchronised recipients, of which 40 became pregnant (80%) and 38 progressed all the way to term, delivering 86 live kids. The present study indicates that LOPU-IVEP can be used successfully to extend the reproductive life of valuable goats that have acquired difficulties becoming pregnant by artificial insemination after multiple kiddings.


Assuntos
Transferência Embrionária/veterinária , Fertilização in vitro/veterinária , Cabras/fisiologia , Laparoscopia/veterinária , Doação de Oócitos/veterinária , Fatores Etários , Animais , Feminino , Cabras/genética , Cabras/cirurgia , Masculino , Doação de Oócitos/métodos , Gravidez
6.
Med Sci Sports Exerc ; 38(3): 463-71, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16540833

RESUMO

PURPOSE: We investigated the effects of muscle length during stretch-shortening cycles (SSC) in vivo on changes in MGF gene expression and quantitative morphometry in rat skeletal muscle. METHODS: Dorsiflexor muscles of male Sprague-Dawley rats were exposed to seven sets of 10 SSC at 500 degrees .s(-1). Animals were randomly assigned to a long muscle length injury group (L-inj), short muscle length injury group (S-inj), or isometric group (Iso), with recoveries examined at 6 or 48 h post-injury for each group. Following exposure, animals were euthanized, and the tissue was prepared for either histology (quantitative morphometry) or RNA isolation, followed by quantitative real-time reverse transcriptase polymerase chain reaction. mRNA levels were measured for mechano-growth factor (MGF), while 18S ribosomal RNA served as the internal reference sample. RESULTS: Stereological measures indicative of edema and myofiber degeneration were significantly increased in the L-inj SSC group at 48 h when compared with the S-inj or Iso group. MGF mRNA was increased transiently at 6 h in the isometric group. In contrast, MGF mRNA was increased at 48 h in the S-inj, but was not increased at either time point in the L-inj group. CONCLUSION: These data strongly indicate that exposure to SSC at longer muscle lengths result in greater morphometric indices of inflammation and degeneration than SSC conducted at a shorter muscle lengths or isometric contractions, at the same time that the adaptation to SSC was prolonged and, apparently, not resolved in the L-inj group that was manifested by the lack of up-regulation in MGF mRNA.


Assuntos
Expressão Gênica/genética , Contração Isométrica/fisiologia , Sistema Musculoesquelético/lesões , Animais , Masculino , Sistema Musculoesquelético/fisiopatologia , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , West Virginia
7.
Zygote ; 11(3): 219-27, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14640186

RESUMO

The objective of this study was to assess the efficacy of a novel intracytoplasmic sperm injection (ICSI) procedure, as well as the in vitro and in vivo developmental competence of goat embryos produced by ICSI. Oocyte-cumulus complexes recovered by LOPU from donors stimulated with gonadotrophins were matured in vitro. Fresh goat semen was used for ICSI following Percoll gradient washing. Tail-cut spermatozoa were microinjected into the ooplasm of goat oocytes using a piezo micropipette-driving system (PiezoDrill). In order to assess developmental competence, the ICSI-derived zygotes were cultured in one of two media systems (mTALP-mKSOM vs G1.3-G2.3) for in vitro development or were transferred into recipients for full-term development. The results suggest that cutting sperm tails using the oocyte-holding pipette coupled with the PiezoDrill is an efficient approach for goat ICSI in terms of oocyte survival, pronuclear development and initial cleavage. The mTALP-mKSOM culture system was more suitable for in vitro development of ICSI-derived goat embryos than G1.3-G2.3. This first report of full-term development of an ICSI-derived goat embryo suggests that ICSI can be applied to assisted reproduction in goats.


Assuntos
Desenvolvimento Embrionário e Fetal/fisiologia , Injeções de Esperma Intracitoplásmicas/métodos , Animais , Blastocisto/fisiologia , Técnicas de Cultura de Células/métodos , Células Cultivadas , Transferência Embrionária , Feminino , Cabras , Masculino , Microinjeções , Oócitos/citologia , Oócitos/fisiologia , Gravidez , Taxa de Gravidez , Cauda do Espermatozoide , Espermatozoides/fisiologia
8.
Childs Nerv Syst ; 17(10): 584-8, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11685519

RESUMO

BACKGROUND: Neurenteric cysts are rare congenital lesions of the spine and are lined with entodermal epithelium. They result from anomalous endodermal-neuroectodermal adhesion in the 3rd week of embryonic life with persistence of canal of Kovalevsky. The nature of the eventual abnormality depends on the extent to which this adhesion subsequently disappears. Persistence of the entire tract results in the extreme form of combined anterior and posterior spina bifida with dorsal enteric fistula and persistence of only a part of the tract producing the isolated intraspinal cyst. The most common location is the cervico-dorsal region, and usually it lies ventral to the spinal cord. The lumbosacral location is uncommon. Associated vertebral anomalies, gut cysts, bowel duplication, the presence of keratin markers and mucin-secreting cuboidal or columnar intestinal epithelium in their walls confirm their entodermal origin. PATIENTS: We describe here three unusual cases of neurenteric cysts in patients aged 5-18 years who had already had symptoms for some time. One of these had a cyst sited predominantly in the sacral canal, another presented with a lumbar neurenteric cyst, and the third patient had an intradural extramedullary thoracic lesion. Two of these children had associated anomalies, the one with lumbar cyst also having a lipomeningomyelocele and spina bifida while the other also had deformed vertebrae. All three patients underwent laminectomy and gross excision of the cysts through a posterior approach. RESULTS AND CONCLUSION: The diagnosis of neurenteric cysts was confirmed by demonstrating mucin-producing cuboidal or columnar epithelium lining the cystic cavity.


Assuntos
Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural/cirurgia , Coluna Vertebral/cirurgia , Adolescente , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Região Lombossacral , Imageamento por Ressonância Magnética , Masculino , Defeitos do Tubo Neural/patologia , Disrafismo Espinal/diagnóstico , Coluna Vertebral/patologia
9.
Med Vet Entomol ; 15(3): 346-9, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11583455

RESUMO

The effectiveness of two pyrethroids, fenvalerate and deltamethrin, against the fly Haematobia irritans exigua de Meijere (Diptera: Muscidae) on buffalo was considered in a field trial. Fenvalerate provided 100% control for 1, 2 and 4 weeks at concentrations of 0.03, 0.04 and 0.05%, respectively. Concentrations of 0.01 and 0.02% were less effective. One hundred percent control of this fly was obtained with deltamethrin for 2, 3 and 6 weeks at concentrations of 0.003, 0.004 and 0.005%, respectively. Deltamethrin concentrations of 0.001% and 0.002% achieved fly control for only 1-2 weeks, respectively.


Assuntos
Búfalos/parasitologia , Controle de Insetos/métodos , Inseticidas/administração & dosagem , Muscidae/crescimento & desenvolvimento , Piretrinas/administração & dosagem , Administração Tópica , Animais , Índia , Nitrilas
10.
J Leukoc Biol ; 69(1): 3-10, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11200064

RESUMO

Stimulation of macrophages by a variety of agents causes activation of mitogen-activated protein kinases (MAPKs). Activation of MAPKs by lipopolysaccharide involves CD14 and Toll receptors. Subsequent steps still remain to be explored. Tumor necrosis factor-alpha (TNF-alpha)-induced activation of MAPKs has been shown to involve the death domain proteins (TRADD, FADD, MADD) and TRAFs. Other molecules involved in this pathway include the protein kinases, ASK1, germinal center kinase (GCK), hematopoietic progenitor kinase 1 (HPK1), and GCK-related kinase (GCKR). Although, these pathways have been described in various cell types, their role in macrophages remains to be established. The availability of knockout mice and constitutively active and dominant-negative mutants of MAPKs should greatly enhance our understanding of this field. The activation of MAPKs seems to be different in cell lines compared with primary cells. Among the macrophages, cells from different compartments show different expression of receptors and signal transduction molecules. These differences may account for differences in MAPK activation and other phenotypic differences in macrophages from different compartments. Therefore, it is important to use primary cells for studying MAPK signal-transduction pathways, and the data from cell lines should not be extrapolated to primary cells.


Assuntos
Ativação de Macrófagos/fisiologia , Macrófagos/fisiologia , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Animais , Humanos , Sistema de Sinalização das MAP Quinases , Transdução de Sinais
11.
J Toxicol Environ Health A ; 61(7): 623-39, 2000 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-11127416

RESUMO

The objectives of this investigation were to study the effects of hypo- and hyperthyroidism on some factors involved in lung injury under basal conditions (air exposure) and during an inflammatory response induced by inhalation exposure to lipopolysaccharide (LPS; 100 microg/ml; 3 h) in adult rats. Thyroid status was altered by thyroidectomy or thyroxine injections for 15 d. Hyperthyroidism alone caused a greater degree of lung cell damage, an increase in the permeability of the alveolar-capillary barrier, a rise in the total number of phagocytic cells obtained by bronchoalveolar lavage (BAL), and enhanced nitric oxide (NO) release by phagocytic cells relative to that in euthyroid control animals. Hypothyroidism alone was associated with opposite effects. Exposure of animals to LPS produced inflammatory responses, which included significant increases in lung cell damage, permeability of the alveolar-capillary barrier, number of phagocytic cells obtained by BAL, and NO production by the phagocytic cells. In general, hyperthyroidism enhanced the effects of LPS, while hypothyroidism reduced LPS-induced responses. These results suggest that thyroid status alone can affect some of the factors involved in lung injury and also modulate some of the inflammatory effects of LPS. Hyperthyroidism tends to enhance lung injury, while hypothyroidism seems to reduce lung injury.


Assuntos
Hipertireoidismo/patologia , Hipotireoidismo/patologia , Lipopolissacarídeos/toxicidade , Pulmão/patologia , Albuminas/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/citologia , Capilares/patologia , Contagem de Células , Permeabilidade da Membrana Celular/efeitos dos fármacos , Endotoxinas/farmacologia , L-Lactato Desidrogenase/metabolismo , Masculino , Óxido Nítrico/metabolismo , Fagócitos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Tiroxina/toxicidade
12.
J Gerontol A Biol Sci Med Sci ; 55(11): M649-57, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11078094

RESUMO

BACKGROUND: Dysregulation of immunologic and coagulation systems is common in elderly persons and is associated with many diseases of aging. Thrombotic events are a major cause of morbidity and mortality in the elderly population. This study assesses whether D-dimer, a marker of fibrinolytic activity, varies systematically by demographic, health, and functional measures, and derives a prediction model for factors related to D-dimer in a sample of community-dwelling elderly persons. METHODS: D-dimer levels were assessed in a random sample of 1,727 community-dwelling elderly persons from five rural and urban counties in North Carolina in 1992, as part of the Established Populations for the Epidemiologic Studies of the Elderly (Duke University). All subjects were 72 years or older at the time of the blood draw. In addition, all subjects were surveyed yearly by telephone or in person each year from 1986 to 1992 for a variety of health, functional, and social factors. Levels of D-dimer in 1992 were related cross-sectionally to demographics (age, race, education, income, gender, smoking), function (Nagi, Rosow-Breslau, Katz, Older Americans Resources and Services procedures instrumental activities of daily living), life satisfaction and self-rated health, self-reported diseases (heart attack, cancer, stroke, diabetes, and hypertension), and weight change from 1986 to 1992. RESULTS: D-dimer levels increased with increasing age and functional disability. Among the health variables, only high blood pressure was predictive of D-dimer level. D-dimer levels were dramatically higher in blacks. Blacks were nearly four times more likely to have an extreme value of D-dimer (>600 microg/l) than whites when high D-dimer (yes/no) was analyzed, and blacks had an average level that was nearly 40% higher than whites in analyses of the continuous version of the outcome. This racial effect was not substantively affected in multivariable analyses with demographic and socioeconomic variables controlled. Race, age, functional status, current smoking, high blood pressure, and weight loss were related to level of D-dimer, and race, age, and functional status were related to the presence of a high D-dimer level (in the top 10% of the sample). CONCLUSIONS: Black, older, and functionally impaired persons had significantly higher levels of D-dimer in this sample of community-dwelling elderly persons. The findings for race were particularly striking and persisted even after controlling for smoking and other factors known to be related to thrombosis and were not mediated by social factors. This result may contribute to our understanding of the increased levels of thrombotic events found in these groups.


Assuntos
Envelhecimento/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Idoso , Idoso de 80 Anos ou mais , População Negra , Humanos , Trombose/etiologia , População Branca
13.
In Vitr Mol Toxicol ; 13(1): 5-16, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10900403

RESUMO

Chronic inhalation of hard metal (WC-Co) particles causes alveolitis and the eventual development of pulmonary fibrosis. The initial inflammatory response includes a change in the alveolar epithelial cell-capillary barrier, which has been shown to be regulated by the state of assembly and organization of the actin cytoskeletal network. The objective of this study was to evaluate the effect WC-Co particles have on F-actin organization of lung epithelial cells in an in vitro culture system. Rat lung epithelial (L2) cells were exposed to 5, 25, and 100 microg/mL of WC-Co particles, as well as the individual components (Co and WC) of the hard metal mixture particles for 24 h. The effect on F-actin organization was visualized by laser scanning confocal microscopy (LSCM) following Bodipy-Phallacidin staining. Minimal changes in the F-actin microfilaments of L2 cells were observed by LSCM after exposure to WC and WC-Co at 5 and 25 microg/mL, while at 100 microg/mL, there was a noticeable disruption in the uniform distribution of L2 cell F-actin microfilaments. After exposure to Co, a dose-dependent change in the F-actin organization of the L2 cells was observed. Little change in F-actin assembly was observed after treatment with 5 microg/mL of Co (the concentration equivalent to the 5% amount of Co commonly present in 100 microg/mL of the WC-Co sample mixture). However, at 100 microg/mL of Co, the microfilaments aggregated into homogeneous masses within the cells, and a significant loss in the organization of L2 F-actin was observed. These dramatic alterations in F-actin organization seen after exposure to the higher doses of Co were attributed to an increase in L2 cell injury as measured by lactate dehydrogenase and trypan blue exclusion. We conclude the pulmonary response evoked in the lung by inhalation of high levels of WC-Co particles is unlikely due to alterations in the F-actin microfilaments of lung-epithelial cells.


Assuntos
Actinas/metabolismo , Citoesqueleto/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Metais Pesados/toxicidade , Citoesqueleto de Actina/efeitos dos fármacos , Ligas/administração & dosagem , Ligas/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cobalto/administração & dosagem , Cobalto/toxicidade , Citoesqueleto/metabolismo , Citoesqueleto/patologia , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Corantes Fluorescentes , L-Lactato Desidrogenase/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Metais Pesados/administração & dosagem , Microscopia Confocal , Microscopia de Contraste de Fase , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Ratos , Compostos de Tungstênio/administração & dosagem , Compostos de Tungstênio/toxicidade
14.
Artigo em Inglês | MEDLINE | ID: mdl-10711324

RESUMO

Inducible nitric oxide synthase (iNOS) has been shown to be present in a variety of cell types, and nitric oxide (NO) has been implicated in a multitude of biological functions. The purpose of this review is twofold: (1) to provide a comprehensive table of cell types that produce NO together with the effects of agents used to study iNOS regulation, as a ready reference for the investigators in the field; and (2) to summarize recent observations dealing with iNOS signal transduction mechanisms. Initially, the major regulation of NO production was believed to occur at the transcription step, but now it is recognized that NO regulation can occur at the transcriptional, posttranscriptional, translational, and posttranslational level. There have been a number of studies of the regulation of iNOS in various cell types, often yielding conflicting results. The major emphasis of this review is on iNOS signal transduction mechanisms. For example, the role of JAK kinases and mitogen-activated protein (MAP) kinases in iNOS regulation is elaborated. In addition, species differences in the iNOS promoter region and the role of RNA structure in iNOS expression is discussed. The role MAP kinases play in translational regulation in addition to transcriptional regulation is emphasized. An analysis of the current data and suggestions for future studies are also presented.


Assuntos
Óxido Nítrico Sintase/metabolismo , Animais , Linhagem Celular , Regulação Enzimológica da Expressão Gênica , Humanos , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Fosfotransferases/fisiologia , Regiões Promotoras Genéticas , RNA Mensageiro/química , Fatores de Transcrição/fisiologia
15.
Am J Physiol ; 276(1): L186-96, 1999 01.
Artigo em Inglês | MEDLINE | ID: mdl-9887071

RESUMO

The objectives of this investigation were 1) to report that pulmonary surfactant inhibits lipopolysaccharide (LPS)-induced nitric oxide (. NO) production by rat alveolar macrophages, 2) to study possible mechanisms for this effect, and 3) to determine which surfactant component(s) is responsible. NO produced by the cells in response to LPS is due to an inducible. NO synthase (iNOS). Surfactant inhibits LPS-induced. NO formation in a concentration-dependent manner;. NO production is inhibited by approximately 50 and approximately 75% at surfactant levels of 100 and 200 microg phospholipid/ml, respectively. The inhibition is not due to surfactant interference with the interaction of LPS with the cells or to disruption of the formation of iNOS mRNA. Also, surfactant does not seem to reduce. NO formation by directly affecting iNOS activity or by acting as an antioxidant or radical scavenger. However, in the presence of surfactant, there is an approximately 80% reduction in the amount of LPS-induced iNOS protein in the cells. LPS-induced. NO production is inhibited by Survanta, a surfactant preparation used in replacement therapy, as well as by natural surfactant. NO formation is not affected by the major lipid components of surfactant or by two surfactant-associated proteins, surfactant protein (SP) A or SP-C. However, the hydrophobic SP-B inhibits. NO formation in a concentration-dependent manner;. NO production is inhibited by approximately 50 and approximately 90% at SP-B levels of 1-2 and 10 microgram/ml, respectively. These results show that lung surfactant inhibits LPS-induced. NO production by alveolar macrophages, that the effect is due to a reduction in iNOS protein levels, and that the surfactant component responsible for the reduction is SP-B.


Assuntos
Lipopolissacarídeos/farmacologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Surfactantes Pulmonares/farmacologia , Animais , Inibidores Enzimáticos/farmacologia , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Proteolipídeos/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Espermina/metabolismo
16.
Indian J Ophthalmol ; 47(4): 229-31, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10892478

RESUMO

PURPOSE: To study the optic disc size in eyes with ocular hypertension (OHT) in comparison to primary open-angle glaucoma (POAG) and normals. METHODS: Optic disc photographs obtained with the Nidek 3dx NM camera were digitized (Nikon coolscan) and disc area calculated using Littmann correction in a randomly chosen eye of 28 OHT, 42 POAG and 30 normal subjects. OHT was defined as increased intraocular pressure with no disc or field changes suggestive of glaucoma with open angles. RESULTS: The optic disc area in OHT was 9.47 +/- 1.09 mm2; 12.27 +/- 2.87 mm2 in POAG; and 12.11 +/- 2.83 mm2 in normal individuals. CONCLUSION: Using magnification corrected morphometry and the criteria for OHT diagnosis, the optic disc area in OHT was significantly smaller (p < 0.0001) in POAG and normals.


Assuntos
Hipertensão Ocular/patologia , Disco Óptico/patologia , Glaucoma de Ângulo Aberto/patologia , Humanos , Pressão Intraocular , Fotografação , Prognóstico , Campos Visuais
17.
J Gerontol A Biol Sci Med Sci ; 52(4): M201-8, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9224431

RESUMO

BACKGROUND: IL-6 is a multifunctional cytokine that has been shown to increase with age. METHODS: Plasma IL-6 was measured by ELISA in 1,727 community-dwelling elderly subjects whose blood was drawn during the third in-person survey of the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). Demographics, functional status (disability), and disease states were determined. Correlations of these factors with IL-6 were analyzed with Spearman's Rho while differences between groups were assessed by Wilcoxon test. RESULTS: IL-6 levels were higher with age (p = .0001) even in this older population (> 70 years). There was a positive correlation between IL-6 and functional disability for each of the functional status measures (p = .0001), as well as a correlation between self-rated health and IL-6. Significantly higher median levels of IL-6 were found in subjects reporting prevalent cancer, heart attack, and high blood pressure, but not diabetes or arthritis. The association between age and functional status with high IL-6 remained when all other variables were controlled, in multivariable analysis. CONCLUSIONS: This association between increased plasma IL-6 levels and functional status suggests that dysregulation of IL-6 may be related to the functional disability seen with aging, and that IL-6 may be useful as a component of an overall marker of health.


Assuntos
Medicina Comunitária/métodos , Pessoas com Deficiência , Interleucina-6/sangue , Idoso , Envelhecimento/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Nível de Saúde , Humanos , Masculino , Análise Multivariada , Autoavaliação (Psicologia)
18.
Am J Med Sci ; 313(3): 131-7, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9075429

RESUMO

Adhesion molecule expression on peripheral blood leukocytes from diabetic patients with severe retinopathy and age-matched control subjects was assessed. Expression of CD11b, CD18, and L-selectin was measured on granulocytes and lymphocytes in whole blood within 1 hour of blood collection. Adhesion molecule expression was determined at 4 degrees C, 37 degrees C, and after stimulation with one of the chemotactic peptides, N-formyl-methionyl-leucyl-phenyl-alanine or beta-phorbol 12-myristate 13-acetate. There were no differences between diabetics and controls in CD11b expression in neutrophils at 4 degrees C, 37 degrees C, or after N-formyl-methionyl-leucyl-phenylalanine stimulation. However, during stimulation with beta-phorbol 12-myristate 13-acetate, the increase in CD11b expression in neutrophils from patients with diabetes was significantly less than in controls. In neutrophils, there was no difference between the control and diabetic participants in CD18 expression at 4 degrees C, but after warming the cells to 37 degrees C, the expression was significantly higher in patients with diabetes. The difference became even more apparent after N-formyl-methionyl-leucyl-phenyl-alanine stimulation. The increase in CD18 expression after beta-phorbol 12-myristate 13-acetate stimulation of neutrophils was similar in control and diabetic participants. There was no difference in L-selectin expression in neutrophils under any conditions. There was no difference in adhesion molecule expression on lymphocytes under similar conditions. In summary, these observations indicate that integrin expression of neutrophils from patients with diabetes and retinopathy is altered after stimulation with neutrophil-activating agents. The changes were integrin-, stimulus-, and cell-specific, which suggests that the signal transduction mechanisms may be altered in diabetic neutrophils. These alterations may be responsible for abnormal leukocyte/endothelial interactions and microvascular complications in diabetic retinopathy.


Assuntos
Retinopatia Diabética/sangue , Integrinas/sangue , Neutrófilos/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD18/sangue , Feminino , Humanos , Selectina L/sangue , Antígeno de Macrófago 1/análise , Masculino , Pessoa de Meia-Idade , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Acetato de Tetradecanoilforbol/farmacologia
19.
Indian J Psychiatry ; 39(1): 61-3, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21584046

RESUMO

EEG was recorded from right and left frontal leads during bilateral (n=11) and unilateral (n=l4) ECTs. The seizure EEG was analyzed using East Fourier 'Transform and the spectral power oj the Delta (1-4 Hz) band was computed. The spectral power on both sides was similar in the bilateral ECT. Unilateral ECT produced asymmetry in the early - (first 8 seconds after stimulus offset) and mid - (17-32 seconds after the stimulus offset) siezure phases; the spectral power was lower on the unstimulated hemisphere. Studies to elucidate the relevance of EEG delta band of the seizure to therapeutic potency of ECT are suggested.

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