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1.
Network ; 34(4): 221-249, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37606050

RESUMO

In order to guarantee the desired quality of machined products, a reliable surface roughness assessment is essential. Using a surface profile metre with a contact stylus, which can produce accurate measurements of surface profiles, is the most popular technique for determining the surface roughness of machined items. One of the limitations of this technique is the work piece surface degradation brought on by mechanical contact between the stylus and the surface. Hence, in this paper, a roughness assessment technique based on the suggested Taylor-Gorilla troops optimizer-based Deep Neuro-Fuzzy Network (Taylor-GTO based DNFN) is proposed for estimating the surface roughness. Pre-processing, data augmentation, feature extraction, feature fusion, and roughness estimation are the procedures that the suggested technique uses to complete the roughness estimate procedure. Roughness estimation is performed using DNFN that has been trained using Taylor-GTO, which was created by combining the Taylor series with the Gorilla troop's optimizer. The created Taylor-GTO based DNFN model has minimum Mean Absolute Error, Mean Square Error, and RMSE of 0.403, 0.416, and 1.149, respectively.


Assuntos
Aprendizado Profundo , Gorilla gorilla , Animais , Propriedades de Superfície
2.
J Assoc Physicians India ; 61(9): 600-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24772694

RESUMO

BACKGROUND: Influenza A(H1N1) infection affected Indian population in 2009. Patients needed ICU admission and monitoring. OBJECTIVES: To describe and correlate clinical and radiographic features of Influenza A(H1N1) infection in patients hospitalised in Intensive care unit. MATERIAL AND METHODS: Retrospective study of records of 100 RT-PCR confirmed patients with Influenza A(H1N1) infection from August 2009 to March 2010 was done. Each patient underwent an evaluation to determine clinical and radiographic features. RESULTS: Mean age of the patients was 33.43 years (+/- 12.152) with maximum patients between 18-40 years, with 53% males and 43% females. Cough (96%), Fever (95%), breathlessness (83%), throat pain (34%), crepitations (69%), Tachypnoea (59%)were the prominent symptoms and signs. 61% (n = 63) had comorbid condition like pregnancy (n = 13,20.63%), Diabetes Mellitus (DM) (n = 12,19.05%), HT (n = 11,17.60%), Obesity (n = 10, 15.87%) and Rheumatic Valvular Heart Disease (RVHD) (n = 6,09.52%). Chest X ray was abnormal in 91% patients and normal in 09% pts. Bilateral findings were seen in 61.53% cases. Most common zones affected were lower zones (77.46%), then middle zones (71.42%), followed by upper zones (42.7%). Most common patterns were consolidation (64.83%), reticulonodular (24.17%) and nodular (10.98%). 27.47% had two, 21.97% had four, 19.78% had three,12.08% had six, 7.69% had five and 10.98% had single zone involvement. Fever, cough and tachypnoea were present in all 100% pts with nodular pattern while crepitations were observed in 79.66% cases of consolidation. Patchy consolidation was seen in comorbidities like pregnancy (n = 10) and obesity (n = 06), while reticulonodular pattern was observed in hypertensive patients (n = 06). Maximum number of deaths were between 21 and 30 years of age (60.71%). Total number of deaths were 28 with 60.71% (n = 17) deaths between 21 and 30 years of age. Deaths were more in presence of comorbidities like Pregnancy (n = 5, 17.85%), Hypertension (n = 4,14.28%), Diabetes (n = 3 10.21%) and RVHD (n = 3,10.71%), in presence of RLZ involvement (92.85%), RMZ (89.28%), LMZ (85.21%) and RUZ involvement (71.42%), with consolidation pattern (57.14%) followed by reticulonodular pattern (21.42%) and in presence of six zone involvement (36.37%) followed by four zone (35%) and then by three(33%) and two (32%) zone involvement. Mean duration of hospital stay was 9.1 days. 23% patients stayed for less than 5 days, 41% stayed between 9 and 14 days while only 7% required to stay for more than 15 days. 37% pts showed normal Xray at the time of discharge or death. 38% patients showed persistence of radiological lesion at discharge or death. CONCLUSIONS: Young to middle age patients were commonly affected. Common comorbidities were Pregnancy, Diabetes, Hypertension, and Obesity and patients had fever, cough, breathlessness, tachypnoea, crepitations as common clinical features. Radiologically it was multizonal, bilateral disease with predominant lower zone involvement and common patterns were consolidation followed by reticulonodular and nodular. Patchy consolidation was more common in pregnancy and obesity while reticulonodular pattern was more in hypertensive patients. Fever, cough and tachypnoea were present in all 100% pts with nodular pattern. Crepitations were common in pts with consolidation. Clinical recovery preceded radiological recovery. Young to middle aged individuals died more. Deaths were more in presence of comorbidities like Pregnancy, HT, DM and RVHD, also with RLZ, RMZ, LMZ involvement and with consolidation pattern and with six zone involvement.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/diagnóstico por imagem , Adolescente , Adulto , Comorbidade , Diagnóstico Diferencial , Surtos de Doenças , Feminino , Humanos , Índia/epidemiologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Unidades de Terapia Intensiva , Masculino , Radiografia Torácica , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco
3.
Artigo em Inglês | MEDLINE | ID: mdl-20578524

RESUMO

Melioidosis, which is mainly prevalent in Thailand and Australia, has shown an increasing trend in India in the last few years. We carried out a retrospective study of 25 culture-proven adult cases of melioidosis who were admitted to a tertiary care hospital in southern India during June 2001 to September 2007. There was a six-fold increase in the number of cases in 2006 and 2007 as compared to 2001. Diabetes mellitus was the predisposing factor in 68% of cases, followed by alcoholism (28%). The clinical presentations were fever (80%), pneumonia and/or pleural effusion (48%), hepatomegaly (56%), joint involvement, and/or osteomyelitis (48%), splenomegaly (40%), splenic abscess (24%) and septicemia (28%). The organism, Burkholderia pseudomallei, was sensitive to co-amoxiclav, cotrimoxazole, ceftazidime, and carbapenem. The study suggests that melioidosis is an emerging infectious disease in the southwestern coastal belt of India, and it is likely to happen at much higher incidence.


Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Melioidose/epidemiologia , Adolescente , Adulto , Idoso , Doenças Transmissíveis Emergentes/terapia , Complicações do Diabetes/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Masculino , Melioidose/terapia , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco
4.
J Mol Biol ; 222(1): 89-98, 1991 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-1942070

RESUMO

Electron microscope images of frozen-hydrated crystals of a proteolytically modified fibrinogen show excellent preservation of the structure. An electron density map of the key centric projection of the crystal at 18 A resolution has been obtained by combining the phases derived from cryo-electron microscopy with X-ray amplitudes. Simulation methods developed in earlier studies have been used to interpret the map. In contrast to the earlier images, the map allows us to visualize the coiled-coil region of the molecule and possible substructure in the beta domains. The map also shows that there is a marked difference in density in the two regions corresponding to the molecular ends where the gamma domains interact. A possible interpretation of this finding is provided by assuming substructure in the gamma domains and the breaking of molecular symmetry where these domains interact. Some additional constraints useful for the determination of the three-dimensional structure were obtained from cryo-electron micrographs of a perpendicular view at 25 A resolution. Implications of this working model for the molecular length and contacts in the filaments in both the crystal and fibrin are described. The data used here will be valuable as a starting point for obtaining the three-dimensional structure.


Assuntos
Fibrinogênio/química , Simulação por Computador , Cristalização , Fibrina/química , Fibrina/ultraestrutura , Fibrinogênio/ultraestrutura , Congelamento , Microscopia Eletrônica , Difração de Raios X
5.
Immunol Res ; 17(1-2): 253-9, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9479586

RESUMO

Lymphomagenesis is viewed as a multistep process involving many independent transforming events. From several lines of investigation, it is speculated that in many cases, the early transforming events take place at a very early stage of B cell development. The focus of our laboratory is to understand the physiologic processes that ensure the development of normal B cells. It follows then that when one such process at an early stage of development is aberrant, the B cell will be prone to transformation events and dysregulated expansion.


Assuntos
Linfócitos B/imunologia , Genes de Imunoglobulinas , Cadeias Pesadas de Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/imunologia , Animais , Linfócitos B/patologia , Diferenciação Celular/imunologia , Transformação Celular Neoplásica/imunologia , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética
6.
Neuropharmacology ; 44(5): 562-72, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12668042

RESUMO

The mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine (MPEP) produces anxiolytic or antidepressant effects in several rodent models through incompletely described mechanisms. Anxiolytics and antidepressants share several neuroendocrine features, including acute activation of the hypothalamic-pituitary-adrenal (HPA)-axis, desensitization of neuroendocrine responses with repeated dosing, and desensitization of the HPA axis to 5-HT1A agonist stimulation. We characterized these neuroendocrine parameters in rats treated systemically with MPEP and compared them to those induced by the anxiolytic buspirone. Acutely, MPEP dose-dependently (0.1-10 mg/kg i.p.) increased plasma corticosterone concentrations. These responses were blocked by 50% with the 5-HT1A antagonist WAY100635. The corticosterone responses to both 3 mg/kg MPEP and buspirone were decreased by 80% after 5 days of twice-daily injections. Repeated injection with MPEP decreased HPA-axis sensitivity to buspirone challenge by 75%. This desensitization was not associated with changes in mGluR5 or 5-HT1A receptor binding properties, expression of G-protein subunits coupled to these receptors, or in 5-HT-stimulated binding of [(3)H]-GTPgammaS to membranes. We conclude that MPEP acutely disinhibits the HPA axis, in part through uncharacterized changes in serotonergic signaling. Desensitization of 5-HT1A responses after repeated MPEP administration may indicate that, like other anxiolytics and antidepressants, plasticity in 5-HT signal transduction pathways has occurred.


Assuntos
Antagonistas de Aminoácidos Excitatórios/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Serotonina/farmacologia , Animais , Relação Dose-Resposta a Droga , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor de Glutamato Metabotrópico 5 , Receptores de Glutamato Metabotrópico/metabolismo , Receptores de Serotonina/metabolismo , Receptores 5-HT1 de Serotonina , Serotonina/metabolismo , Agonistas do Receptor de Serotonina/farmacologia
7.
Neuropharmacology ; 34(8): 871-86, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8532169

RESUMO

We have isolated and characterized overlapping cDNAs that encode two isoforms of the human metabotropic glutamate receptor subtype 5 (hmGluR5). The deduced amino acid sequences of human and rat mGluR5a are 94.5% identical. However, a region in the putative cytoplasmic domain (SER926-ALA1121) displays significant sequence divergence. Genomic analysis of this region showed that the sequence divergence results from species-specific differences in the genomic sequences, not from alternative splicing. The distribution of mGluR5 mRNA in human brain was most strongly detected throughout the hippocampus, with moderate levels in the caudate-putamen, cerebral cortex, thalamus, and deep cerebellar nuclei, and at low levels in the cerebellar cortex. Activation of both hmGluR5a and hmGluR5b transiently expressed in Xenopus oocytes and HEK293 cells was coupled to inositol phosphate (InsP) formation and elevation of the intracellular free calcium ([Ca2+]i). The agonist rank order of potency for activating recombinant hmGluR5a receptors in either system was quisqualate > L-glutamate > 1S,3R-ACPD. Both the quisqualate stimulated InsP and [Ca2+]i were inhibited by (+)-MCPG. Recombinant human mGluR5a was also stably expressed in mouse fibroblast Ltk- cells, in which the efficacy and potency of quisqualate were unchanged for more than 30 cell passages.


Assuntos
Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Animais , Sequência de Bases , Cálcio/metabolismo , DNA Complementar/biossíntese , Eletrofisiologia , Fibroblastos , Ácido Glutâmico/metabolismo , Humanos , Immunoblotting , Hibridização In Situ , Inosina Trifosfato/biossíntese , Camundongos , Dados de Sequência Molecular , Oócitos/metabolismo , Testes de Precipitina , Ratos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transfecção , Xenopus laevis
8.
Neuropharmacology ; 38(10): 1493-503, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10530811

RESUMO

In the present paper we describe 2-methyl-6-(phenylethynyl)-pyridine (MPEP) as a potent, selective and systemically active antagonist for the metabotropic glutamate receptor subtype 5 (mGlu5). At the human mGlu5a receptor expressed in recombinant cells, MPEP completely inhibited quisqualate-stimulated phosphoinositide (PI) hydrolysis with an IC50 value of 36 nM while having no agonist or antagonist activities at cells expressing the human mGlu1b receptor at concentrations up to 30 microM. When tested at group II and III receptors, MPEP did not show agonist or antagonist activity at 100 microM on human mGlu2, -3, -4a, -7b, and -8a receptors nor at 10 microM on the human mGlu6 receptor. Electrophysiological recordings in Xenopus laevis oocytes demonstrated no significant effect at 100 microM on human NMDA (NMDA1A/2A), rat AMPA (Glu3-(flop)) and human kainate (Glu6-(IYQ)) receptor subtypes nor at 10 microM on the human NMDA1A/2B receptor. In rat neonatal brain slices, MPEP inhibited DHPG-stimulated PI hydrolysis with a potency and selectivity similar to that observed on human mGlu receptors. Furthermore, in extracellular recordings in the CA1 area of the hippocampus in anesthetized rats, the microiontophoretic application of DHPG induced neuronal firing that was blocked when MPEP was administered by iontophoretic or intravenous routes. Excitations induced by microiontophoretic application of AMPA were not affected.


Assuntos
Encéfalo/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Piridinas/farmacologia , Receptores de Glutamato Metabotrópico/fisiologia , Animais , Animais Recém-Nascidos , Encéfalo/efeitos dos fármacos , Linhagem Celular , AMP Cíclico/metabolismo , Guanosina 5'-O-(3-Tiotrifosfato)/farmacocinética , Humanos , Cloreto de Lítio/farmacologia , Masculino , Metoxi-Hidroxifenilglicol/análogos & derivados , Metoxi-Hidroxifenilglicol/farmacologia , Oócitos/fisiologia , Fosfatidilinositóis/metabolismo , Ácido Quisquálico/farmacologia , Ensaio Radioligante , Ratos , Ratos Endogâmicos , Ratos Sprague-Dawley , Receptor de Glutamato Metabotrópico 5 , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Receptores de Glutamato Metabotrópico/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/genética , Proteínas Recombinantes/antagonistas & inibidores , Radioisótopos de Enxofre , Transfecção , Xenopus laevis
9.
J Nucl Med ; 41(6): 1108-13, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10855643

RESUMO

UNLABELLED: A pretreatment with a single dose of an immunoconjugate (IC) that promises to enhance tumor uptake and decrease liver uptake of radiolabeled monoclonal antibodies (MAbs) might be of use in radioimmunodetection and radioimmunotherapy (RIT). We have shown previously that an interferon (IFN)-MAb (1:1) immunoconjugate (IC) enhances tumor uptake by a factor of 2 or more and reduces liver uptake by 50% in nude mice bearing human tumors. The aim of this study was to determine whether IFN modulates antigenic expression and to ascertain the most effective route of its administration, the optimal quantity to be administered, and the optimal duration of time to lapse between the administration of IC and the radiolabeled MAb. METHODS: IFN-alpha-2b and anticarcinoembryonic antigen-F6 (IgG2a) MAb were conjugated (1:1), and F(ab')2 of the MAb was labeled with 99mTc. Human colorectal tumors were grown in nude mice by implanting 5 x 10(6) LS174T confluent cells grown in culture. Mice, 5 in each group, received 20 x 10(3) IU intravenously, intramuscularly, or intraperitoneally and 40 x 10(3), 60 x 10(3), and 80 x 10(3) IU intravenously 30 min before the intravenous administration of 25.9 MBq 99mTc/20 microg F(ab')2. Mice in the control groups received 99mTc-F(ab')2 but not the conjugate. Twenty-four hours later mice were killed and imaged, and tissues were removed for quantitative (percentage injected dose/g [% ID/g]) distribution of 99mTc. RESULTS: In all conjugate-receiving mice, the tumor uptake was higher and the liver uptake was lower (P < 0.01) than that in the control mice with the exception of liver uptake, which was not significantly different in mice receiving 80 x 10(3) IU conjugate. The optimal results were apparent in mice pretreated with 40 x 10(3) IU conjugate in which tumor uptake was enhanced by a factor of 2.3 (4.8 +/- 0.5 %ID/g versus 11 +/- 0.7 %ID/g; P < 0.01). The renal uptake remained unchanged, and the tumor-to-muscle ratios increased from 11.5 +/- 6.8 to 14.6 +/- 3.9, and the tumor-to-blood ratios increased from 4.4 +/- 1.8 to 8.3 +/- 2.4. The liver uptake decreased from 9.5% +/- 1% to 5% +/- 1.6%. Results were attributed to enhanced tumor blood flow, increased antigenic expression, and blocking of hepatic nonspecific Fc receptors. CONCLUSION: A pretreatment with IFN-MAb conjugate is a worthwhile approach to consider in radioimmunoscintigraphy and RIT.


Assuntos
Imunoconjugados/uso terapêutico , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Radioimunodetecção , Radioimunoterapia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacocinética , Antígeno Carcinoembrionário/imunologia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/radioterapia , Relação Dose-Resposta a Droga , Imunoconjugados/farmacocinética , Fatores Imunológicos/farmacocinética , Interferon alfa-2 , Interferon-alfa/farmacocinética , Fígado/diagnóstico por imagem , Fígado/metabolismo , Camundongos , Camundongos Nus , Transplante de Neoplasias , Compostos de Organotecnécio/farmacocinética , Proteínas Recombinantes , Distribuição Tecidual
10.
Am J Cardiol ; 84(4): 470, A9, 1999 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-10468091

RESUMO

Diagnostic electrophysiologic studies and defibrillator implantations with subsequent test discharges from the defibrillator do not cause an elevation in cardiac troponin I levels. All patients with an ablation had an elevation in the cardiac troponin I levels.


Assuntos
Ablação por Cateter , Creatina Quinase/metabolismo , Desfibriladores Implantáveis , Eletrocardiografia , Infarto do Miocárdio/diagnóstico , Miocárdio/metabolismo , Troponina I/metabolismo , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/terapia , Biomarcadores , Cardioversão Elétrica , Humanos , Isoenzimas , Infarto do Miocárdio/metabolismo , Valor Preditivo dos Testes
11.
Cancer Chemother Pharmacol ; 15(1): 20-5, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-4006045

RESUMO

Since the male antifertility drug, gossypol, was shown to be a specific inhibitor of DNA synthesis at moderately low doses in cultured cells, its antitumor potential has been evaluated in three murine tumor models. The effects of gossypol on tumor growth and the survival of 10- to 12-week-old BDF1 mice bearing mouse mammary adenocarcinoma 755 (Ca 755) or P388 or L1210 leukemias, all injected IP, were measured. At an optimum dose of 0.5 mg/mouse given as a single injection at 2 days (48 h) after the inoculation of 10(5) Ca 755 tumor cells, gossypol rendered 66% of the mice free of tumor cells, whereas the remaining 34% died of drug toxicity. The survival rate decreased sharply at doses on either side of the optimum. At suboptimal doses a major proportion of the tumor-bearing mice died of tumor, whereas at higher doses all the animals died of drug toxicity. In other words, the effective dose range of gossypol was rather narrow. The rapidly proliferating mouse leukemias, P388 and L1210, failed to respond to gossypol. Histopathological studies of various organs in the gossypol-treated mice revealed no consistent lesions that could give an indication of organ-specific toxicity of gossypol. The reduction in the myeloid series in the bone marrow of gossypol-treated mice may have been due to depletion rather than direct toxic effect. Further studies are essential to evaluate this compound with regard to its antitumor activity in other murine models.


Assuntos
Gossipol/uso terapêutico , Neoplasias Experimentais/tratamento farmacológico , Animais , Contagem de Células , Esquema de Medicação , Avaliação de Medicamentos , Feminino , Gossipol/toxicidade , Leucemia L1210/tratamento farmacológico , Leucemia P388/tratamento farmacológico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Camundongos , Neoplasias Experimentais/patologia , Cavidade Peritoneal/patologia
12.
FEMS Immunol Med Microbiol ; 15(1): 27-34, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8871113

RESUMO

Mycobacterium avium complex (MAC) infection is the most common disseminated opportunistic infection encountered in patients with AIDS. We have studied the ability of specific Mycobacterium avium (MA) antigen to stimulate human monocyte-derived macrophages (MDM) to produce tumor necrosis factor-alpha (TNF-alpha). MDM stimulated with MA sonicate, MA 68 kDa and MA 48-52 kDa antigens were found to produce TNF-alpha in a dose-dependent manner. Reverse transcriptase-polymerase chain reaction analysis of mRNA extracts from antigen-stimulated MDM indicated that TNF-alpha mRNA expression was of brief duration and the time point of peak TNF-alpha mRNA levels was found to be antigen-specific. A significant difference in TNF-alpha production in response to MA 48-52 kDa antigen and M. bovis 65 kDa antigen was observed between MDM from normal and HIV positive individuals.


Assuntos
Antígenos de Bactérias/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Complexo Mycobacterium avium/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Humanos , Infecção por Mycobacterium avium-intracellulare/imunologia
13.
FEMS Immunol Med Microbiol ; 29(1): 1-7, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10967253

RESUMO

Clinical strains of Mycobacterium avium isolated from patients with acquired immunodeficiency syndrome, but not a non-clinical laboratory strain (ATCC 25291), were found to stimulate the human alveolar epithelial cell line A549, to produce monocyte chemoattractant protein (MCP)-1. A549 cells were also found to produce elevated levels of MCP-1 in response to sonicates of the clinical strains of M. avium, and surprisingly, the non-clinical strain as well. However, sonic extracts of the clinical strains were found to induce significantly higher levels of MCP-1 production compared to extracts of the non-clinical strain (P < 0.001). These data suggest the existence of strain-related differences in antigen expression by M. avium. The clinical and non-clinical strains of M. avium were found to attach and invade, but not replicate in A549 cells indicating that MCP-1 production by A549 cells does require the presence of viable, replicating organisms. Activation of alveolar epithelial cells by exposure to M. avium resulting in the production of chemokines which recruit inflammatory cells to the site of infection may be an important regulatory pathway for the activation of pulmonary host defense.


Assuntos
Quimiocina CCL2/metabolismo , Complexo Mycobacterium avium/imunologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/microbiologia , Humanos , Complexo Mycobacterium avium/crescimento & desenvolvimento , Alvéolos Pulmonares/imunologia , Alvéolos Pulmonares/microbiologia , Sonicação , Células Tumorais Cultivadas
14.
Artigo em Inglês | MEDLINE | ID: mdl-3222449

RESUMO

1. Hind limb blood flow and arterial blood pressure were recorded during aggressive behaviour induced on electrical stimulation of the anterior hypothalamic area and the central gray, in anaesthetised cats. 2. Bilateral microinfusions of atropine sulphate (20 ug/ul) were made in the midbrain central gray, and the effect on the behavioural and cardiovascular components recorded. 3. Atropine sulphate was found to decrease the hind limb vascular conductance obtained on stimulation of the hypothalamic and the midbrain defence areas. 4. It was found that the recovery of the behavioural components of aggression required at least 1-5 days as compared to the cardiovascular components which reappeared after 3 weeks of atropine sulphate microinfusions. 5. These results suggest that although the cholinergic muscarinic mechanisms play an important role in eliciting both the behavioural and the cardiovascular responses from the same site, yet the two mechanisms may operate differently.


Assuntos
Agressão , Pressão Sanguínea , Hipotálamo Anterior/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Fluxo Sanguíneo Regional , Agressão/efeitos dos fármacos , Animais , Atropina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Gatos , Estimulação Elétrica , Feminino , Membro Posterior/irrigação sanguínea , Masculino , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Receptores Muscarínicos/fisiologia , Valores de Referência , Fluxo Sanguíneo Regional/efeitos dos fármacos
15.
Int Clin Psychopharmacol ; 10(1): 39-43, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7622803

RESUMO

Six neuroleptic (antipsychotic) phenothiazine derivatives which are calmodulin antagonists were tested for their activity against Mycobacterium tuberculosis H37Rv in order to understand their structure-antitubercular activity relationship. Out of the six derivatives tested (trifluoperazine, chlorpromazine, triflupromazine, thioridazine, acetopromazine and fluphenazine), trifluoperazine appears to be a more potent antitubercular drug than others with a minimum inhibitory concentration (MIC) of 5 micrograms/ml. Chlorpromazine, triflupromazine and thioridazine are also active but less potent and have a higher MIC of 20 micrograms/ml. Acetopromazine and fluphenazine could not completely inhibit the growth even at a high concentration of 20 micrograms/ml. These results indicate that a methylpiperazinylpropyl group attached to the nitrogen (position 10) atom and trifluoromethyl group at the second carbon confer antitubercular activity to the phenothiazine molecule. It is suggested that trifluoperazine or one of its derivatives could be useful as one of the drugs in the multi-drug regimen for the treatment of tuberculosis with psychotic problems or vice versa.


Assuntos
Antipsicóticos/farmacologia , Antituberculosos/farmacologia , Calmodulina/antagonistas & inibidores , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Fenotiazinas , Relação Estrutura-Atividade
16.
Carbohydr Res ; 202: 49-66, 1990 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-2224895

RESUMO

The intrinsic reactivity of furanosides bearing activated O-benzyl substituents (3-methoxybenzyl), in the presence of bidentate Lewis acids such as tin(IV) chloride, was explored. These glycosides were found to exhibit extremely interesting chemical properties. Thus, with three reactive substituents (at O-2,3,5), the corresponding glycosides (1 and 7) underwent a novel internal bis-C-arylation process, which involved successive alkylations of the benzyl groups at O-2 and O-3 ("multiple participation"), leading to the formal replacement of the two C-O bonds at the anomeric center of the glycoside by two C-C bonds. The bis-C-arylated constitution of the resulting polycyclic compounds 4 and 8, and the cis configuration of their fused ring system (a tetrahydro-[2]benzopyrano[3,4-d][2]benzoxepin derivative), were determined on the basis of their n.m.r.-spectral parameters. With two 3-methoxybenzyl substituents (at O-3 and O-5, compound 6), intramolecular alkylation of the benzyl group at O-3 or O-5 occurred when glycoside 6 was reacted with titanium(IV) chloride or tin(IV) chloride, respectively, thereby leading to novel bicyclic internal aryl C-glycosides (9 and 12) as major products ("long-range participation"). The constitution of compounds 9 and 12 was unambiguously established by the reactions of analogs of 6 bearing only one 3-methoxybenzyl substituent at a specific position (at O-3: 15; at O-5: 20). The unexpected divergent behavior of 6 in the presence of titanium(IV) and tin(IV) chloride remains to be explained. The availability of compound 9 made it possible to independently prepare the bis-C-arylated derivative 8 (by way of the reverse sequence of internal C-arylation reactions) and thereby to definitively demonstrate its constitution. These unprecedented reactions extend the scope of the intramolecular C-glycosidation of substituted sugars and provide novel methodologies in synthetic carbohydrate chemistry.


Assuntos
Glicosídeos/síntese química , Compostos de Benzil , Fenômenos Químicos , Química , Espectroscopia de Ressonância Magnética , Métodos , Estrutura Molecular
17.
Pediatr Crit Care Med ; 4(2): 252-5, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12749663

RESUMO

OBJECTIVE: To describe extreme hypercalcemia as the presenting feature of acute lymphoblastic leukemia in an 8-yr-old girl and the combined use of pamidronate and calcitonin for its treatment. DESIGN: Case report. SETTING: Pediatric intensive care unit. PATIENT: An 8-yr-old girl with 20.0 mg/dL serum calcium (reference range, 8.8-10.4 mg/dL) and 2.66 mmol/L ionized calcium (reference range, 1.13-1.32 mmol/L). INTERVENTION: Intravenous pamidronate and subcutaneous calcitonin. MEASUREMENTS AND MAIN RESULTS: Our patient presented with nausea, vomiting, lethargy, weight loss, fatigue, and weakness but, remarkably, did not exhibit electrocardiographic changes. Initial treatment with hydration at 8 mL x kg(-1) x hr(-1) and furosemide was ineffective. A single dose of 1 mg/kg intravenous pamidronate given over 24 hrs complemented by three doses of 5 units/kg subcutaneous calcitonin over 36 hrs lowered serum calcium to a normal range within 3 days. Side effects noted were hypocalcemia, hypomagnesemia, and hypophosphatemia. They were most pronounced 7-9 days after treatment, stabilized with supplementation, and returned to acceptable ranges by 1 month without need for ongoing electrolyte supplements. A renal computed tomographic scan did not show nephrocalcinosis. The patient remained free from recurrence of hypercalcemia 6 wks after initiating chemotherapy for acute lymphoblastic leukemia. CONCLUSIONS: Extreme hypercalcemia can be a presenting feature of acute lymphoblastic leukemia, but it may not result in life-threatening organ dysfunction. Combined treatment with pamidronate and calcitonin should be considered for treating hypercalcemia that does not respond to conventional therapy with hydration and furosemide.


Assuntos
Antineoplásicos/uso terapêutico , Calcitonina/uso terapêutico , Difosfonatos/uso terapêutico , Hipercalcemia/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Criança , Feminino , Humanos , Hipercalcemia/etiologia , Pamidronato , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Resultado do Tratamento
18.
Carbohydr Res ; 196: 41-58, 1990 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-2346943

RESUMO

"Internal" C-glycosylarenes [e.g., (2R,3S,3aS,9bR)-3,3a,5,9b-tetrahydro-3-methoxy- and -3,7-dimethoxy-2-methoxymethyl-2H-furo[3,2-c][2]benzopyran] were prepared by intramolecular reactions of 2-O-benzyl derivatives of methyl 3,5-di-O-methyl-D-xylofuranoside (2) and their conversion into authentic C-glycosylated aromatic systems was investigated. The auxiliary benzylic linkage could not be cleaved by hydrogenolysis; isochroman derivatives (e.g., (3S)-3,4-dihydro-3-[(1R,2R)-2-hydroxy-1,3-dimethoxypropyl]-5-metho xy-1H- 2-benzopyran) were obtained under these conditions. However, oxidation of the primary benzylic position with ruthenium tetraoxide gave the corresponding lactone (a dihydroisocoumarin derivative, e.g., (2R,3S,3aS,9bR)-2,3,3a,9b-tetrahydro-3,7-dimethoxy-2-methoxy - methyl-5H-furo[3,2-c][2]benzopyran-5-one) which could be opened by saponification, thereby leading to a stereochemically unique C-glycosylbenzoic acid derivative. The same type of lactone was obtained directly from a derivative of 2 bearing a sufficiently reactive benzoyl group at O-2 (3,5-dimethoxybenzoyl); this process provides a useful approach to a heterocyclic system present in a variety of natural products. In related studies, the 2-O-phenyl substituent was found to be much less reactive than the 2-O-benzyl group in intramolecular Friedel-Crafts reactions of 2-O-substituted glycofuranosides. The first examples of successful internal C-arylation in the pyranoid series were achieved from 2-O-(3-methoxybenzyl)-D- mannopyranosides; the resulting "internal C-glycosides" [( 2R,3S,4S,4aS,10bS)-2,3,4,4a,6,10b- hexahydro-3,4,8-trimethoxy-2-methoxymethylpyrano[3,2-c][2]benzopyr an and 3,4-bis(benzyloxy)-2-benzyloxymethyl-8-methoxy analog] contain a heterocyclic skeleton closely related to that of the natural product bergenin.


Assuntos
Benzopiranos/síntese química , Compostos de Benzil , Carboidratos , Alquilação , Glicosilação , Oxirredução
19.
Talanta ; 19(1): 67-71, 1972 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18961026

RESUMO

A selective analytical extraction method for rapid successive complexometric determination of thorium(IV) and uranium(VI) in sulphuric acid media is described. The method is based on the extraction of thorium and uranium from sulphuric acid media with N-butylaniline or N-benzylaniline in chloroform. Both thorium and uranium are selectively and quantitatively extracted in the presence of ascorbic acid and EDTA. Most cations and anions do not interfere. The reduction of uranium(VI) with sodium dithionite at room temperature is rapid and quantitative and superior to that with ascorbic acid, which reduces uranium(VI) in boiling solution. The method is simple, rapid and accurate, and the experimental conditions are not highly critical.

20.
Talanta ; 21(6): 411-5, 1974 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18961477

RESUMO

A simple and rapid method is proposed for the separation of tervalent gallium, indium and thallium by solvent extraction with N-benzylaniline in chloroform from different concentrations of hydrochloric acid. Thallium and gallium are extracted from 1M and 7.0-7.5M hydrochloric acid respectively. Indium is finally extracted from hydriodic acid. These metals in the final extracts are determined complexometrically. Interference from some cations can easily be eliminated by reduction with sulphite, followed by selective oxidation of thallium(I) to thallium(III) with saturated bromine water, and from others by the use of thioglycollic acid as a masking agent in the extraction of gallium and indium. Most common anions cause no interference. Log-log plots of distribution coefficients vs. concentration of amine for gallium, indium and thallium indicate a 2:1 limiting mole ratio of amine to these metals.

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