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1.
Perfusion ; 29(1): 53-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23863493

RESUMO

A 50-year-old man was admitted to the intensive care unit with respiratory failure and shock after suffering a massive overdose of amlodipine, lisinopril and hydrochlorothiazide. Despite mechanical ventilation, vasopressors, calcium gluconate, hyperinsulinemia-euglycemia therapy, methylene blue and intravenous fat emulsion, the patient's respiratory and hemodynamic status deteriorated. Venoarterial extracorporeal membrane oxygenation (ECMO) was initiated to provide cardiopulmonary support in the setting of profound respiratory failure and refractory shock. The patient was placed on ECMO 19 hours after arrival to the hospital, after which vasopressor and ventilatory requirements decreased significantly. The patient was decannulated from ECMO after 8 days and was discharged home after a 56-day hospitalization. Early institution of ECMO should be considered for the management of respiratory failure and refractory shock in the setting of calcium channel blocker overdose when medical therapies are insufficient.


Assuntos
Anlodipino/intoxicação , Oxigenação por Membrana Extracorpórea/métodos , Hidroclorotiazida/intoxicação , Lisinopril/intoxicação , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Insuficiência Respiratória/terapia , Resultado do Tratamento
2.
Curr Oncol ; 26(4): e571-e573, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31548826

RESUMO

Objective: Immune checkpoint inhibitors are now a standard of care for the management of many metastatic cancers, including non-small-cell lung cancer. Pembrolizumab, a selective anti-PD-1 monoclonal antibody, augments the host antitumoural response. This hyperactivation of the immune system has side effects, the so-called immune-related adverse effects. The objective of this case report was to review and point out a new pattern of immune checkpoint inhibitor-associated pneumonitis. Case Description: A 69-year-old woman with stage iv non-small-cell lung cancer receiving pembrolizumab presented for increased dyspnea. Pembrolizumab-related obstructive bronchiolitis was diagnosed based on a new severe obstructive disorder, without bronchodilator reversibility, and mosaic attenuation on angiography, without other identifiable causes. Summary: To our knowledge, this is the first description of a case of pembrolizumab-induced obstructive bronchiolitis. Various patterns of immune checkpoint inhibitor-associated lung disease have been described, and bronchiolitis should be included in the differential diagnosis.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Bronquiolite Obliterante/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Bronquiolite Obliterante/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X
3.
Mol Cell Biol ; 20(17): 6579-86, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10938132

RESUMO

Retinoic acid (RA) is required for diverse developmental programs, including vertebral specification. Both RA receptor disruption and excess RA result in homeotic transformations of the axial skeleton. These effects are believed to occur through altered expression of Hox genes, several of which have been demonstrated to be direct RA targets. Members of the cdx (caudal) homeobox gene family are also implicated in regulating Hox expression. Disruption of cdx1 results in vertebral homeotic transformations and alteration of Hox expression boundaries; similar homeosis is also observed in cdx2 heterozygotes. In Xenopus, gain or loss of Cdx function affects vertebral morphogenesis through a mechanism that also correlates with altered Hox expression. Taken together with the finding of putative Cdx binding motifs in several Hox promoters, these data strongly support a role for Cdx members in direct regulation of expression of at least some Hox genes. Most retinoid-responsive Hox genes have not been demonstrated to be direct RA targets, suggesting that intermediaries are involved. Based on these findings, we hypothesized that one or more cdx members may transduce the effects of RA on Hox transcription. Consistent with this, we present evidence that cdx1 is a direct RA target gene, suggesting an additional pathway for retinoid-dependent vertebral specification.


Assuntos
Proteínas Aviárias , Proteínas de Homeodomínio/metabolismo , Retinoides/metabolismo , Tretinoína/metabolismo , Proteínas de Xenopus , Animais , Northern Blotting , Fator de Transcrição CDX2 , Células Cultivadas , Cruzamentos Genéticos , DNA Complementar/metabolismo , Proteínas de Homeodomínio/genética , Hibridização In Situ , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutagênese , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , Receptores do Ácido Retinoico/metabolismo , Fatores de Tempo , Transfecção , Células Tumorais Cultivadas , Regulação para Cima
4.
J Mol Endocrinol ; 36(3): 449-61, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16720716

RESUMO

Aldo-keto reductases (AKRs) are multifunctional enzymes capable of acting on a wide variety of substrates, including sex steroids. AKRs having 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) activity can reduce progesterone to 20alpha-hydroxy-4-pregnen-3-one (20alpha-DHP), a metabolite with lower affinity for the progesterone receptor. The objective of this study was to investigate the regulation of equine AKR1C23 during human chorionic gonadotropin (hCG)-induced ovulation/luteinization. The equine AKR1C23 cDNA was cloned and shown to encode a 322 amino acid protein that is conserved (71-81% identity) when compared with mammalian orthologs. RT-PCR/Southern blotting analyses were performed to study the regulation of AKR1C23 transcripts in equine preovulatory follicles isolated between 0 and 39 h after hCG treatment (ovulation occurring 39-42 h post-hCG). Results showed the presence of low AKR1C23 expression before hCG treatment, but a marked increase was observed in follicles obtained 12 h after hCG (P<0.05). Analyses of isolated preparations of granulosa and theca interna cells identified low mRNA expression in both cell types prior to hCG treatment, with granulosa cells clearly being the predominant site of follicular AKR1C23 mRNA induction. A specific polyclonal antibody was raised against a fragment of the equine protein and immunoblotting analyses showed an increase in AKR1C23 protein in granulosa cell extracts when comparing follicles isolated at 36 h post-hCG vs those collected prior to treatment, in keeping with mRNA results. Immunohistochemical data confirmed the induction of the enzyme in follicular cells after hCG treatment. The enzyme was tested for 20alpha-HSD activity and was shown to exhibit a K(M) of 3.12 microM, and a V(max) of 0.86 pmol/min per 10 microg protein towards progesterone. The levels of 20alpha-DHP measured in follicular fluid reflected this activity. Collectively, these results demonstrate for the first time that the gonadotropin-dependent induction of follicular luteinization is accompanied by an increase in AKR1C23 expression. Considering the 20alpha-HSD activity of AKR1C23, its regulated expression in luteinizing preovulatory follicles may provide a biochemical basis for the increase in ovarian 20alpha-DHP observed during gonadotropin-induced luteinization/ovulation. (The nucleotide sequence reported in this paper has been submitted to GenBank with accession number AY955082.).


Assuntos
20-Hidroxiesteroide Desidrogenases/metabolismo , Gonadotropina Coriônica/metabolismo , Indução Enzimática/fisiologia , Regulação Enzimológica da Expressão Gênica , Luteinização/fisiologia , Folículo Ovariano/enzimologia , 20-Hidroxiesteroide Desidrogenases/genética , 20-alfa-Di-Hidroprogesterona/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Feminino , Cavalos , Humanos , Dados de Sequência Molecular , Folículo Ovariano/citologia , Folículo Ovariano/metabolismo , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Distribuição Tecidual
7.
Vet Hum Toxicol ; 46(6): 312-3, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15587246

RESUMO

The Vietnamese centipede (Scolopendra subspinipes) is one of the largest and most aggressive tropical centipedes. It has become a popular pet among arthropod enthusiasts and the general public. Despite their reputation, few well-documented cases of envenomation are reported in the medical literature. A 53-yo man developed severe pain, swelling and erythema of his left hand and forearm after being bitten on the hand by his pet Vietnamese centipede. The neurological and vascular examination of the arm was normal. He was admitted to the hospital, treated with arm elevation, analgesics and parenteral antibiotics. His symptoms gradually resolved and he was discharged after 4 d with no neurological or cosmetic sequelae.


Assuntos
Artrópodes , Mordeduras e Picadas/diagnóstico , Animais , Mordeduras e Picadas/patologia , Mordeduras e Picadas/terapia , Tratamento de Emergência , Mãos , Humanos , Masculino , Pessoa de Meia-Idade , Vietnã
8.
Mol Cell Biochem ; 173(1-2): 25-32, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9278251

RESUMO

UV cross-linking studies of the natriuretic peptide receptor-B (NPR-B) using radiolabeled C-type natriuretic peptide (CNP) indicate that only fully glycosylated receptors are capable of binding ligand. We therefore used site-directed mutagenesis to determine which potential glycosylation sites are occupied by carbohydrate, and the relevant mutants were characterized in order to understand the function of carbohydrate addition at those sites. Our results suggest that five of seven potential N-linked glycosylation sites are modified. In addition, mutation of asparagine 24 results in a loss of approximately 90% of receptor activity. This mutant is expressed at levels comparable to the wild-type receptor, and its activity is not significantly different from that of wild-type NPR-B in terms of EC50 for CNP. Ligand binding studies on this mutant further show that although there is no change in affinity for ligand, approximately 90% of receptor binding is lost. These data suggest that many of the mutant receptors are simply not properly folded. Our results indicate that glycosylation of asparagine 24 of NPR-B receptors may be critical for the formation of a competent ligand binding domain.


Assuntos
Asparagina/metabolismo , Células COS/metabolismo , Guanilato Ciclase , Ligantes , Ligação Proteica/fisiologia , Receptores do Fator Natriurético Atrial/metabolismo , Sequência de Aminoácidos , Animais , Ligação Competitiva , Western Blotting , Metabolismo dos Carboidratos , Bovinos , Reagentes de Ligações Cruzadas , GMP Cíclico/biossíntese , Glicosilação , Radioisótopos do Iodo/metabolismo , Dados de Sequência Molecular , Mutação/genética , Mutação/fisiologia , Peptídeo Natriurético Tipo C , Ligação Proteica/efeitos da radiação , Estrutura Terciária de Proteína , Proteínas/metabolismo , Receptores do Fator Natriurético Atrial/química , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Valores de Referência , Homologia de Sequência de Aminoácidos , Raios Ultravioleta
9.
Biochemistry ; 34(7): 2130-6, 1995 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-7857923

RESUMO

The atrial natriuretic R1 receptor is a membrane protein that is present as an apparently preassociated noncovalent oligomer in the absence of ligand as suggested by steric exclusion studies and cross-linking experiments in physiological and recombinant receptor expression systems. The association state of this receptor oligomer was studied in the presence of amiloride and ATP, two known modulators of the R1 receptor functions with both the intact receptor and a cytoplasmic domain-deleted form obtained by limited proteolysis with trypsin. It was shown by steric exclusion on Superose 6 column that amiloride increased the affinity of ANF for the native and truncated receptor, in contrast with ATP, whose destabilizing effect on ANF binding was abolished by truncation of the cytoplasmic domain. Neither amiloride nor ATP exerts its effects by altering the aggregation state of the receptor. Comparison of the measured number of ANF binding sites with immunoassayable receptor protein revealed that the stoichiometry of ANF binding to the R1 receptor was 1:2. This was confirmed by using an ANF analog that bears a photoactivatable group at both of its ends, showing that ANF, as for the growth hormone/receptor complex, interacts with both the receptor subunits and specifically cross-links a dimeric form of the receptor. The potential pharmacological consequences of this 1:2 stoichiometric ratio of the ANF-receptor complex are discussed.


Assuntos
Fator Natriurético Atrial/metabolismo , Guanilato Ciclase/química , Receptores do Fator Natriurético Atrial/química , Zona Glomerulosa/metabolismo , Trifosfato de Adenosina/farmacologia , Amilorida/farmacologia , Sequência de Aminoácidos , Animais , Bovinos , Reagentes de Ligações Cruzadas , Citoplasma , Guanilato Ciclase/metabolismo , Técnicas In Vitro , Substâncias Macromoleculares , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/imunologia , Agregação de Receptores/efeitos dos fármacos , Receptores do Fator Natriurético Atrial/metabolismo , Relação Estrutura-Atividade
10.
Ann Rech Vet ; 20(1): 65-72, 1989.
Artigo em Francês | MEDLINE | ID: mdl-2930135

RESUMO

In a flock of 2,000 ewes located in an endemic area of Brucella melitensis infection, subjected to systematic vaccination of lambs either with killed and adjuvanted B. melitensis H.38 vaccine from 1973 to 1978, or with living B. melitensis Rev.1 vaccine since 1979, reactions to allergic intrapalpebral test, complement fixation test and Rose Bengal plate test were recorded in small groups of animals vaccinated four, three, two or one years ago. Four years after H.38 vaccination, 39 ewes out of 40 (97%) remained positive at least to one of the three tests. After vaccination with strain Rev.1, 16% out of 153 ewes vaccinated one to four years before were positive. These results were discussed according to two aspects: 1) infectious or vaccinal origins of these positive reactions; 2) consequences on implement of test and slaughter procedures in a vaccinated flock: allergic or complement fixation tests would have led to eliminate 9% out of ewes vaccinated with the Rev.1 vaccine, but only 1% with the Rose Bengal plate test.


Assuntos
Anticorpos Antibacterianos/análise , Vacina contra Brucelose , Brucella/imunologia , Brucelose/veterinária , Doenças dos Ovinos/prevenção & controle , Ovinos/imunologia , Animais , Brucelose/epidemiologia , Brucelose/imunologia , Feminino , Seguimentos , Doenças dos Ovinos/epidemiologia
11.
Dev Biol ; 240(1): 46-60, 2001 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11784046

RESUMO

Exogenous retinoic acid (RA) can evoke vertebral homeosis when administered during late gastrulation. These vertebral transformations correlate with alterations of the rostral limit of Hox gene expression in the prevertebrae, suggesting that retinoid signaling regulates the combinatorial expression of Hox genes dictating vertebral identity. Conversely, loss of certain RA receptors (RARs) results in anterior homeotic transformations principally affecting the cervical region. Despite these observations, the relationship between retinoid signaling, somitic Hox expression, and vertebral patterning is poorly understood. The members of the murine Cdx family (Cdx1, Cdx2, and Cdx4) are the homologues of Drosophila caudal and encode homeobox-containing transcription factors. Cdx1 homozygous null mutants exhibit anterior homeotic transformations, some of which are reminiscent of those in RARgamma null offspring. In Cdx1 mutants, these transformations occur concomitant with posteriorized prevertebral expression of certain Hox genes. Cdx1 has recently been demonstrated to be a direct RA target, suggesting an indirect means by which retinoid signaling may impact vertebral patterning. To further investigate this relationship, a complete allelic series of Cdx1-RARgamma mutants was generated and the skeletal phenotype assessed either following normal gestation or after administration of RA. Synergistic interactions between these null alleles were observed in compound mutants, and the full effects of exogenous RA on vertebral morphogenesis required Cdx1. These findings are consistent with a role for RA upstream of Cdx1 as regards axial patterning. However, exogenous RA attenuated several defects inherent to Cdx1 null mutants. This finding, together with the increased phenotypic severity of RARgamma-Cdx1 double null mutants relative to single nulls, suggests that these pathways also function in parallel, likely by converging on common targets.


Assuntos
Padronização Corporal/fisiologia , Proteínas de Homeodomínio/fisiologia , Receptores do Ácido Retinoico/fisiologia , Vertebrados/embriologia , Animais , Sequência de Bases , Primers do DNA , Regulação da Expressão Gênica no Desenvolvimento/genética , Genes Homeobox , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Camundongos , Camundongos Knockout , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Receptor gama de Ácido Retinoico
12.
J Biol Chem ; 276(36): 34323-30, 2001 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-11448962

RESUMO

Prostaglandin E(2) (PGE(2)) is thought to be an ultimate prostaglandin effector during the ovulatory process, and the objectives of this study were to clone bovine PGE synthase (PGES) and to characterize its regulation by gonadotropins in preovulatory follicles in vivo. The bovine PGES complementary DNA (cDNA) was shown to contain a 5'-untranslated region of eight base pairs (bp), an open reading frame of 462 bp and a 3'-untranslated region of 406 bp. The putative bovine PGES open reading frame encodes a 153-amino acid protein that is 85, 78, and 78% identical to the human, rat, and mouse PGES homologs, respectively. The regulation of PGES during ovulation was studied using three different models in vivo: 1) human chorionic gonadotropin (hCG)-induced ovulation during a normal estrous cycle; 2) hCG-induced ovulation following ovarian hyperstimulation; and 3) spontaneous ovulation during natural estrus. Results from semi-quantitative reverse transcription-polymerase chain reaction/Southern blotting analyses showed that the hCG/luteinizing hormone surge caused a significant increase in PGES mRNA. Levels of PGES transcripts were low or undetectable prior to hCG/luteinizing hormone but increased markedly 18-24 h after hCG in models 1 and 2, and 18-24 h after the onset of natural estrus in model 3 (p < 0.05). Analyses on isolated preparations of granulosa and theca interna cells indicated that the granulosa cell layer was the predominant site of follicular PGES expression. The regulation of the protein was studied in the same models using a specific antibody raised against a fragment of bovine protein (Delta PGES; from Glu(49) to Val(146)). Results from immunoblots showed an induction of bovine PGES (M(r) = 17,000) 18-24 h after hCG treatment or onset of estrus (p < 0.05). The protein was detected in extracts of granulosa cells but not in theca interna. Collectively, these results demonstrate that the ovulatory process is associated with a gonadotropin-dependent induction of PGES in granulosa cells of ovarian follicles in vivo, thus establishing for the first time the regulation of the enzyme in a physiological context.


Assuntos
Gonadotropinas/metabolismo , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Folículo Ovariano/metabolismo , Ovulação , Regiões 3' não Traduzidas , Regiões 5' não Traduzidas , Sequência de Aminoácidos , Animais , Anticorpos/metabolismo , Sequência de Bases , Southern Blotting , Bovinos , Gonadotropina Coriônica/química , Clonagem Molecular , DNA Complementar/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Immunoblotting , Oxirredutases Intramoleculares/química , Camundongos , Dados de Sequência Molecular , Fases de Leitura Aberta , Prostaglandina-E Sintases , RNA Mensageiro/metabolismo , Ratos , Homologia de Sequência de Aminoácidos , Fatores de Tempo , Distribuição Tecidual , Regulação para Cima
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