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1.
J Investig Allergol Clin Immunol ; 33(1): 37-44, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35416154

RESUMO

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.


Assuntos
Asma , Produtos Biológicos , Pólipos Nasais , Rinite , Sinusite , Humanos , Omalizumab/uso terapêutico , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Olfato , Produtos Biológicos/uso terapêutico , Anosmia/complicações , Anosmia/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Asma/complicações , Asma/tratamento farmacológico , Imunossupressores/uso terapêutico , Sinusite/complicações , Sinusite/tratamento farmacológico , Doença Crônica , Rinite/complicações , Rinite/tratamento farmacológico
3.
Sci Rep ; 13(1): 18269, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880377

RESUMO

Angiotensin II receptor 1(AT1) antagonists are beneficial in focal ischemia/reperfusion (I/R). However, in cases of global I/R, such as cardiac arrest (CA), AT1 blocker's potential benefits are still unknown. Wistar male rats were allocated into four groups: Control group (CG)-animals submitted to CA by ventricular fibrillation induced by direct electrical stimulation for 3 min, and anoxia for 5 min; Group AT1 (GAT1)-animals subjected to CA and treated with 0.2 mg/kg of candesartan diluted in dimethylsulfoxide (DMSO) (0.1%); Vehicle Group (VG): animals subjected to CA and treated with 0.2 ml/kg of DMSO and Sham group (SG)-animals submitted to surgical interventions, without CA. Cardiopulmonary resuscitation consisted of group medications, chest compressions, ventilation, epinephrine (20 mcg/kg) and defibrillation. The animals were observed up to 4 h after spontaneous circulation (ROSC) return, and survival rates, hemodynamic variables, histopathology, and markers of tissue injury were analyzed. GAT1 group had a higher rate of ROSC (62.5% vs. 42.1%, p < 0.0001), survival (100% vs. 62.5%, p = 0.027), lower incidence of arrhythmia after 10 min of ROSC (10% vs. 62.5%, p = 0.000), and lower neuronal and cardiac injury scores on histology evaluation (p = 0.025 and p = 0.0052, respectively) than GC group. The groups did not differ regarding CA duration, number of adrenaline doses, or number of defibrillations. AT1 receptor blockade with candesartan yielded higher rates of ROSC and survival, in addition to neuronal and myocardial protection.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Masculino , Ratos , Animais , Receptor Tipo 1 de Angiotensina , Dimetil Sulfóxido , Ratos Wistar , Parada Cardíaca/terapia , Epinefrina , Modelos Animais de Doenças
4.
Dermatol Online J ; 17(1): 7, 2011 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21272498

RESUMO

A 45-year-old woman with personal history of hypertension presented with an erythematous lesion in the neckline for a year and with a progressive growth. A physical examination revealed an annular lesion with erythematous papules in the edge. Histological exam showed phagocytosis of elastic fibers by multinucleated cells compatible with annular elastolytic giant-cell granuloma. The patient did not present any other associated systemic manifestation. Treatment with tacrolimus 0.1 percent ointment was prescribed with a very good response after two months.


Assuntos
Eritema/patologia , Granuloma de Células Gigantes/patologia , Dermatopatias/patologia , Eritema/tratamento farmacológico , Feminino , Granuloma de Células Gigantes/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Dermatopatias/tratamento farmacológico , Tacrolimo/uso terapêutico
5.
J Evol Biol ; 22(10): 1975-83, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19678864

RESUMO

Cyclical parthenogens, which combine asexual and sexual reproduction, are good models for research into the ecological and population processes affecting the evolutionary maintenance of sex. Sex in cyclically parthenogenetic rotifers is necessary for diapausing egg production, which is essential to survive adverse conditions between planktonic growing seasons. However, within a planktonic season sexual reproduction prevents clonal proliferation. Hence, clones with a low propensity for sex should be selected, becoming dominant in the population as the growing season progresses. In this context, we studied the dynamics of the heritable variation in propensity for sexual reproduction among clones of a Brachionus plicatilis rotifer population in a temporary Mediterranean pond during the period the species occurred in plankton. Clonal isolates displayed high heritable variation in their propensity for sex. Moreover, the frequency of clones with low propensity for sex increased during the growing season, which supports the hypothesized short-term selection for low investment in sex within a growing season. These results demonstrate (1) the inherent instability of the cyclical parthenogenetic life cycle, (2) the cost of sexual reproduction in cyclical parthenogens where sex produces diapausing eggs and (3) the role of the association between sexual reproduction and diapause in maintaining sex in these cyclical parthenogens.


Assuntos
Partenogênese , Rotíferos/genética , Animais , Bioensaio , Reprodução , Rotíferos/fisiologia
6.
J Evol Biol ; 22(12): 2542-53, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19878499

RESUMO

A combination of founder effects and local adaptation - the Monopolization hypothesis - has been proposed to reconcile the strong population differentiation of zooplankton dwelling in ponds and lakes and their high dispersal abilities. The role genetic drift plays in genetic differentiation of zooplankton is well documented, but the impact of natural selection has received less attention. Here, we compare differentiation in neutral genetic markers (F(ST)) and in quantitative traits (Q(ST)) in six natural populations of the rotifer Brachionus plicatilis to assess the importance of natural selection in explaining genetic differentiation of life-history traits. Five life-history traits were measured in four temperature x salinity combinations in common-garden experiments. Population differentiation for neutral genetic markers - 11 microsatellite loci - was very high (F(ST) = 0.482). Differentiation in life-history traits was higher in traits related to sexual reproduction than in those related to asexual reproduction. Q(ST) values for diapausing egg production (a trait related to sexual reproduction) were higher than their corresponding F(ST) in some pairs of populations. Our results indicate the importance of divergent natural selection in these populations and suggest local adaptation to the unpredictability of B. plicatilis habitats.


Assuntos
Variação Genética , Rotíferos/genética , Rotíferos/fisiologia , Adaptação Fisiológica , Animais , Biomarcadores , Feminino , Masculino , Reprodução/fisiologia
7.
Transplant Proc ; 51(2): 383-385, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879547

RESUMO

The plasma cell dyscrasias (PCDs) include a number of entities such as multiple myeloma, primary amyloidosis, and monoclonal immunoglobulin deposition disease. Hematopoietic cell transplant (HCT) is the only cure for a variety of hematologic and oncologic diseases. Clinically significant renal impairment is a common feature in plasma cell myeloma, affecting 20% to 55% of patients at initial diagnosis; 2% to 3% of patients present with failure sufficiently severe to require hemodialysis. This circumstance is associated with a high early mortality. The necessity for immunosuppression after HCT could complicate its management and may precipitate the development of complications. In some patients an effective alternative could be kidney transplant (KT); however, the presence of 2 transplants will require optimal adjustment of immunosuppression and management of complications. At present, there are few published cases of KT after HCT, and the experience of managing 2 transplants is limited. We would like to describe our experience with 4 patients who had a PCD and initially received HCT and received subsequent KT. In our experience the progress and outcome of KT after HCT were optimal. We would like to address that a higher incidence of cytopenia associated with the combination of immunosuppression (lenalidomide, tacrolimus, mycophenolate, etc.) and other drugs (ie, valganciclovir) should be considered together with an increased risk of opportunistic infections and PCD relapse.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Rim , Paraproteinemias/complicações , Paraproteinemias/cirurgia , Insuficiência Renal/cirurgia , Adulto , Idoso , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/etiologia
8.
J Cardiovasc Surg (Torino) ; 47(4): 451-6, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16953165

RESUMO

AIM: The aim of this study was to investigate the association between the presence of ApoE4 and the incidence of postoperative cognitive dysfunction (POCD) after cardiac surgery. METHODS: Eighty-seven adult patients undergoing elective coronary artery bypass graft surgery were observed prospectively at a university tertiary care hospital. All patients were evaluated with the Mini-Mental State Examination (MMSE) and the Glasgow Coma Scale (GCS) for cognitive function and mental status preoperatively, 24 h after surgery and at postoperative day 6. Patients were genotyped for the ApoE polymorphism. The association between ApoE genotype and MMSE evolution was studied by using repeated measures ANOVA. RESULTS: Both the presence of at least one ApoE4 allele and POCD were verified in 21.8% of subjects. The presence of the ApoE4 allele was significantly associated with a worse MMSE score evolution (P=0.04). CONCLUSION: This study suggests an association between ApoE4 and early POCD, but further studies are needed to clarify a causative association. Such new studies should include a more homogenous patient sample and a longer follow-up.


Assuntos
Apolipoproteínas E/genética , Transtornos Cognitivos/sangue , Ponte de Artéria Coronária/efeitos adversos , Doença das Coronárias/cirurgia , DNA/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Apolipoproteína E4 , Apolipoproteínas E/sangue , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/genética , Doença das Coronárias/sangue , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Fatores de Risco
9.
Biochim Biophys Acta ; 1172(3): 346-8, 1993 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-8448214

RESUMO

The promoter of the barley alpha-thionin gene (1.6 kb) fused to the beta-glucuronidase (GUS) gene directs temporally-controlled, tissue-specific expression in the endosperm of transgenic tobacco. The nucleotide sequence of this promoter shows negative regulatory motifs which have been functionally analyzed in other genes.


Assuntos
Hordeum/genética , Proteínas de Plantas/genética , Regiões Promotoras Genéticas , Sequências Reguladoras de Ácido Nucleico , Peptídeos Catiônicos Antimicrobianos , Sequência de Bases , Glucuronidase/genética , Dados de Sequência Molecular , Especificidade de Órgãos , Plantas Geneticamente Modificadas , Plantas Tóxicas , Nicotiana/genética
10.
J Hosp Infect ; 59(4): 299-303, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15749317

RESUMO

Cardiopulmonary bypass and hypothermia (HCPB) is a procedure commonly used during heart surgery, representing a risk factor for the patient by promoting extensive haemodilution and profound physiological changes. Cefuroxime is used for the prevention of infection following heart surgery, and several dose schemes have been suggested for prophylaxis with cefuroxime. The objective of the present study was to assess, in a comparative manner, the systemic availability of cefuroxime administered intravascularly as a bolus dose of 1.5 g to 17 patients having heart surgery with or without HCPB. Plasma cefuroxime concentrations were determined by high-pressure liquid chromatography-UV, and the following values, expressed as medians, were obtained for the study group compared with controls: 69.1 vs. 62.7 mg/L (1st h), 35.8 vs. 26.0mg/L (3rd h), 14.6 vs. 8.7 mg/L (6th h, P<0.05), 6.1 vs. 3.0mg/L (9th h, P<0.05) and 2.6 vs. 1.0mg/L (12th h, P<0.05). Despite the differences recorded during the study period as a consequence of HCPB, low antibiotic concentrations were found as early as 6h post dose for both groups investigated. Thus, the low systemic availability of cefuroxime after the administration of a 1.5-g dose may not protect against postoperative infections. The data obtained permit us to recommend a change in the dose scheme in order to maintain adequate plasma levels of cefuroxime.


Assuntos
Antibacterianos/administração & dosagem , Ponte Cardiopulmonar , Cefuroxima/administração & dosagem , Ponte de Artéria Coronária , Infecção Hospitalar/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Antibacterianos/sangue , Antibacterianos/farmacocinética , Antibioticoprofilaxia , Área Sob a Curva , Cefuroxima/sangue , Cefuroxima/farmacocinética , Cromatografia Líquida de Alta Pressão , Esquema de Medicação , Feminino , Humanos , Controle de Infecções/métodos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Braz J Med Biol Res ; 38(5): 713-21, 2005 05.
Artigo em Inglês | MEDLINE | ID: mdl-15917952

RESUMO

The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG) by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 +/- 8 years, mean weight 75.4 +/- 11.9 kg and mean body surface area 1.83 +/- 0.19 m(2)), receiving propranolol before surgery (80-240 mg a day) and postoperatively (10 mg a day). Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95% CI = 3.9-6.9) to 10.6 h (95% CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95% CI = 3.2-14.3) to 8.3 l/kg (95% CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95% CI = 7.7-24.6) vs 10.7 ml min(-1) kg(-1) (95% CI = 7.7-26.6; NS) after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.


Assuntos
Antagonistas Adrenérgicos beta/farmacocinética , Ponte Cardiopulmonar , Ponte de Artéria Coronária , Doença das Coronárias/sangue , Propranolol/farmacocinética , Antagonistas Adrenérgicos beta/sangue , Adulto , Idoso , Cromatografia Líquida de Alta Pressão , Doença das Coronárias/cirurgia , Feminino , Humanos , Hipotermia Induzida , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Propranolol/sangue
12.
Gene ; 264(2): 163-71, 2001 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-11250071

RESUMO

The genomic organization of STDEFICIENS (STDEF), the potato orthologous gene to DEFICIENS (DEF) from Antirrhinum majus and APETALA3 (AP3) from Arabidopsis thaliana, has been investigated. Southern-blot analysis on genomic DNA from dihaploid potato lines, using 5'-gene specific probes, revealed polymorphisms that were consistent with the existence in potato of at least two copies of STDEF per haploid genome. This was confirmed by the detection of at least six different STDEF transcripts in the common tetraploid potato S. tuberosum. Genes for two of the STDEF loci, here designated as STDEF-1 and STDEF-2, have been identified as corresponding to the previously described pD13 and pD12 genomic clones, respectively (García-Maroto et al., 1993). In addition we have characterised the transcriptional STDEF unit. The main transcription start has been identified around 90 nt upstream of the putative initiation ATG codon, at a CAAATC motif, conserved in AP3. An additional transcription initiation site was detected by 5'-RACE analysis about 300 nt upstream of the main start, which has been confirmed by reverse transcriptase - polymerase chain reaction (RT-PCR) amplification from the longer transcripts. A comparison of the promoter regions for pD12, pD13 and AP3 indicates a similar overall structure, but reveals the existence of a great divergence between pD12 and pD13 in a promoter region that should contain important cis-regulatory elements. This raises the possibility of a differential regulation for the two STDEF genes.


Assuntos
Genes de Plantas/genética , Proteínas de Homeodomínio/genética , Solanum tuberosum/genética , Sequência de Bases , Southern Blotting , Proteína DEFICIENS , DNA Complementar/química , DNA Complementar/genética , DNA de Plantas/genética , Diploide , Genótipo , Dados de Sequência Molecular , Poliploidia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Transcrição Gênica
13.
FEBS Lett ; 296(3): 279-82, 1992 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-1537404

RESUMO

Thionins cause the irreversible inactivation of beta-glucuronidase (GUS) in vitro in a dose- and time-dependent manner. The enzyme is also sensitive to externally added thionins when expressed in the cytoplasmic compartment of tobacco protoplasts transformed with the Gus gene under the 35S promoter of the cauliflower mosaic virus. In protoplasts transformed with the Gus gene fused to a signal peptide, where GUS is translocated into the lumen of the endoplasmic reticulum, the activity is significantly increased both by externally-added and by transiently-expressed thionin, suggesting that it interferes with GUS secretion.


Assuntos
Glucuronidase/antagonistas & inibidores , Proteínas de Plantas/farmacologia , Protoplastos/enzimologia , Peptídeos Catiônicos Antimicrobianos , Eletroforese em Gel de Poliacrilamida , Cinética , Plantas/enzimologia , Plantas/ultraestrutura
14.
J Immunol Methods ; 153(1-2): 99-105, 1992 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-1517607

RESUMO

The influence of two different carriers, poly-L-lysine (PLL) and human serum albumin (HSA) in the binding of specific IgE antibodies to the benzyl penicilloyl hapten (BPO) was determined in a solid-phase assay. Serum samples from patients with a history of immediate reaction to penicillin and which had shown the presence of IgE antibodies to BPO were used. Benzyl penicilloyl derivatized cellulose discs were prepared using PLL of different molecular weight and HSA as carriers. These were treated with different molar ratios of benzyl penicillin. These reagents were compared for uptake of BPO-specific IgE using a pool of sera in a radioallergosorbent test (RAST) type assay. Two PLL systems and two HSA systems were finally compared using 26 individual sera. RAST values were compared by Kruskal-Wallis and Wilcoxon tests. The relationships between the four different assays were evaluated by determining Pearson correlation coefficients and the concordance by determining intraclass correlation coefficients (ICC). Analysis of means by the Wilcoxon test revealed significant differences (P less than 0.01) only when the different carrier assays were compared. The correlation coefficients between all the assays were significant (P less than 0.0001), but the ICC was low when the different carrier assays were compared. These results indicate that the nature of the carriers studied (PLL and HSA) influences the capacity for binding IgE antibodies in the RAST procedure. The differences observed indicate that one conjugate cannot be substituted for the other in the determination of IgE antibodies to BPO and that BPO-PLL is preferable.


Assuntos
Anticorpos/análise , Haptenos/imunologia , Imunoglobulina E/análise , Penicilina G/imunologia , Polilisina/administração & dosagem , Albumina Sérica/administração & dosagem , Humanos , Penicilina G/administração & dosagem , Teste de Radioalergoadsorção
15.
J Heart Lung Transplant ; 15(5): 443-50, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8771498

RESUMO

BACKGROUND: The purpose of this study was to assess the hemodynamic effects of low doses of inhaled nitric oxide in patients after orthotopic heart transplantation. METHODS: Two hours after the operation 10 adult patients who were still under anesthetic effects and undergoing mechanical ventilation inhaled, during 60 minutes, a mixture of nitrogen, oxygen, and nitric oxide (20 ppm). A standard profile of hemodynamic data was collected at baseline, at 30 minutes, at 30 more minutes of inhalation, and at the same points after nitric oxide suspension. RESULTS: A significant decrease was found from baseline to 60 minutes, immediately after nitric oxide inhalation in the following: systemic vascular resistance index 1268 +/- 409 to 1090 +/- 354 (p = 0.0161); pulmonary vascular resistance index 252 +/- 124 to 154 +/- 98 (p < 0.05); pulmonary vascular resistance index/systemic vascular resistance index ratio 0.21 +/- 0.09 to 0.14 +/- 0.08 (p = 0.0025); transpulmonary gradient 12 +/- 3 to 9 +/- 3 (p = 0.05). A significant increase was also found in cardiac index from 4.2 +/- 1.1 to 4.9 +/- 1.4 (p = 0.0007). Other parameters such as mean pulmonary, systemic, wedge and right atrial pressures, in addition to intrapulmonary shunting, heart rate, and oxygen extraction ratio, did not present any significant changes. The procedure was well tolerated by all patients, and no undesirable effects such as methemoglobin elevation or worsening of pulmonary hypertension after nitric oxide suspension were observed. CONCLUSIONS: The beneficial effects observed by inhaled nitric oxide in the pulmonary vascular resistance index/systemic vascular resistance index ratio, transpulmonary gradient, and cardiac index suggest that nitric oxide acts mainly in pulmonary territory and could be a possible pulmonary vasodilator agent used to control central hemodynamics after heart transplantation.


Assuntos
Transplante de Coração , Óxido Nítrico/uso terapêutico , Adulto , Função do Átrio Direito/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Transplante de Coração/fisiologia , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Metemoglobina/análise , Óxido Nítrico/administração & dosagem , Nitrogênio/administração & dosagem , Oxigênio/administração & dosagem , Consumo de Oxigênio/efeitos dos fármacos , Circulação Pulmonar/efeitos dos fármacos , Pressão Propulsora Pulmonar/efeitos dos fármacos , Respiração Artificial , Resistência Vascular/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Vasodilatadores/uso terapêutico
16.
Clin Cardiol ; 23(3): 205-10, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10761810

RESUMO

BACKGROUND: Stimulated endothelium-derived relaxing factor-mediated vasodilation and conduit artery distensibility are impaired in congestive heart failure (CHF). L-arginine could have a potentially beneficial role in CHF, acting through the nitric oxide (NO)-L-arginine pathway or by growth hormone increment. HYPOTHESIS: This study was undertaken to investigate the effects of L-arginine on heart rate, hemodynamics, and left ventricular (LV) function in CHF. METHODS: In seven patients (aged 39 +/- 8 years) with CHF, we obtained the following parameters using echocardiography and an LV Millar Mikro-Tip catheter simultaneously under four conditions: basal, during NO inhalation (40 ppm), in basal condition before L-arginine infusion, and after L-arginine intravenous infusion (mean dose 30.4 +/- 1.9 g). RESULTS: Nitric oxide inhalation increased pulmonary capillary wedge pressure from 25 +/- 9 to 31 +/- 7 mmHg (p < 0.05), but did not change echocardiographic variables or LV contractility by elastance determination. L-arginine decreased heart rate (from 88 +/- 15 to 80 +/- 16 beats/min, p<0.005), mean systemic arterial pressure (from 84 +/- 17 to 70 +/- 18 mmHg, p < 0.007), and systemic vascular resistance (from 24 +/- 8 to 15 +/- 6 Wood units, p<0.003). L-arginine increased right atrial pressure (from 7 +/- 2 to 10 +/- 3 mmHg, p<0.04), cardiac output (from 3.4 +/- 0.7 to 4.1 +/- 0.8 l/min, p < 0.009), and stroke volume (from 40 +/- 9 to 54 +/- 14 ml, p < 0.008). The ratios of pulmonary vascular resistance to systemic vascular resistance at baseline and during NO inhalation were 0.09 and 0.075, respectively, and with L-arginine this increased from 0.09 to 0.12. CONCLUSION: L-arginine exerted no effect on contractility; however, by acting on systemic vascular resistance it improved cardiac performance. L-arginine showed a negative chronotropic effect. The possible beneficial effect of L-arginine on reversing endothelial dysfunction in CHF without changing LV contractility should be the subject of further investigations.


Assuntos
Arginina/farmacologia , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Vasodilatadores/farmacologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Óxido Nítrico/farmacologia , Resistência Vascular/efeitos dos fármacos
17.
Braz J Med Biol Res ; 33(1): 31-42, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10625872

RESUMO

We prospectively evaluated the effects of positive end-expiratory pressure (PEEP) on the respiratory mechanical properties and hemodynamics of 10 postoperative adult cardiac patients undergoing mechanical ventilation while still anesthetized and paralyzed. The respiratory mechanics was evaluated by the inflation inspiratory occlusion method and hemodynamics by conventional methods. Each patient was randomized to a different level of PEEP (5, 10 and 15 cmH2O), while zero end-expiratory pressure (ZEEP) was established as control. PEEP of 15-min duration was applied at 20-min intervals. The frequency dependence of resistance and the viscoelastic properties and elastance of the respiratory system were evaluated together with hemodynamic and respiratory indexes. We observed a significant decrease in total airway resistance (13.12 +/- 0.79 cmH2O l-1 s-1 at ZEEP, 11.94 +/- 0.55 cmH2O l-1 s-1 (P<0.0197) at 5 cmH2O of PEEP, 11.42 +/- 0.71 cmH2O l-1 s-1 (P<0.0255) at 10 cmH2O of PEEP, and 10.32 +/- 0.57 cmH2O l-1 s-1 (P<0.0002) at 15 cmH2O of PEEP). The elastance (Ers; cmH2O/l) was not significantly modified by PEEP from zero (23.49 +/- 1.21) to 5 cmH2O (21.89 +/- 0.70). However, a significant decrease (P<0.0003) at 10 cmH2O PEEP (18.86 +/- 1.13), as well as (P<0.0001) at 15 cmH2O (18.41 +/- 0.82) was observed after PEEP application. Volume dependence of viscoelastic properties showed a slight but not significant tendency to increase with PEEP. The significant decreases in cardiac index (l min-1 m-2) due to PEEP increments (3.90 +/- 0.22 at ZEEP, 3.43 +/- 0.17 (P<0. 0260) at 5 cmH2O of PEEP, 3.31 +/- 0.22 (P<0.0260) at 10 cmH2O of PEEP, and 3.10 +/- 0.22 (P<0.0113) at 15 cmH2O of PEEP) were compensated for by an increase in arterial oxygen content owing to shunt fraction reduction (%) from 22.26 +/- 2.28 at ZEEP to 11.66 +/- 1.24 at PEEP of 15 cmH2O (P<0.0007). We conclude that increments in PEEP resulted in a reduction of both airway resistance and respiratory elastance. These results could reflect improvement in respiratory mechanics. However, due to possible hemodynamic instability, PEEP should be carefully applied to postoperative cardiac patients.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Hemodinâmica/fisiologia , Respiração com Pressão Positiva , Mecânica Respiratória/fisiologia , Adulto , Resistência das Vias Respiratórias/fisiologia , Análise de Variância , Feminino , Humanos , Complacência Pulmonar/fisiologia , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Período Pós-Operatório , Estudos Prospectivos
18.
Braz J Med Biol Res ; 33(5): 509-14, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10775881

RESUMO

We describe a new simple, selective and sensitive micromethod based on HPLC and fluorescence detection to measure debrisoquine (D) and 4-hydroxydebrisoquine (4-OHD) in urine for the investigation of xenobiotic metabolism by debrisoquine hydroxylase (CYP2D6). Four hundred microl of urine was required for the analysis of D and 4-OHD. Peaks were eluted at 8.3 min (4-OHD), 14.0 min (D) and 16.6 min for the internal standard, metoprolol (20 microg/ml). The 5-microm CN-reverse-phase column (Shimpack, 250 x 4.6 mm) was eluted with a mobile phase consisting of 0.25 M acetate buffer, pH 5.0, and acetonitrile (9:1, v/v) at 0.7 ml/min with detection at lambdaexcitation = 210 nm and lambdaemission = 290 nm. The method, validated on the basis of measurements of spiked urine, presented 3 ng/ml (D) and 6 ng/ml (4-OHD) sensitivity, 390-6240 ng/ml (D) and 750-12000 ng/ml (4-OHD) linearity, and 5.7/8.2% (D) and 5.3/8.2% (4-OHD) intra/interassay precision. The method was validated using urine of a healthy Caucasian volunteer who received one 10-mg tablet of Declinax(R), po, in the morning after an overnight fast. Urine samples (diuresis of 4 or 6 h) were collected from zero to 24 h. The urinary excretion of D and 4-OHD, Fel (0-24 h), i.e., fraction of dose administered and excreted into urine, was 6.4% and 31.9%, respectively. The hydroxylation capacity index reported as metabolic ratio was 0.18 (D/4-OHD) for the person investigated and can be compared to reference limits of >12.5 for poor metabolizers (PM) and <12.5 for extensive metabolizers (EM). In parallel, the recovery ratio (RR), another hydroxylation capacity index, was 0.85 (4-OHD: SigmaD + 4-OHD) versus reference limits of RR <0.12 for PM and RR >0. 12 for EM. The healthy volunteer was considered to be an extensive metabolizer on the basis of the debrisoquine test.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Citocromo P-450 CYP2D6/metabolismo , Debrisoquina/análogos & derivados , Debrisoquina/urina , Feminino , Fluorometria/métodos , Humanos , Hidroxilação , Pessoa de Meia-Idade , Fenótipo , Sensibilidade e Especificidade , Xenobióticos/metabolismo
19.
Sao Paulo Med J ; 116(2): 1675-80, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9778887

RESUMO

OBJECTIVES: To determine oxygen derived parameters, hemodynamic and biochemical laboratory data (2,3 Diphosphoglycerate, lactate and blood gases analysis) in patients after cardiac surgery who received massive blood replacement. DESIGN: Prospective study. SETTING: Heart Institute (Instituto do Caração), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Brazil. PARTICIPANTS: Twelve patients after cardiac surgery who received massive transfusion replacement; six of them evolved to a fatal outcome within the three-day postoperative follow-up. MEASUREMENTS AND MAIN RESULTS: The non-survivors group (n = 6) presented high lactate levels and low P50 levels, when compared to the survivors group (p < 0.05). Both groups presented an increase in oxygen consumption and O2 extraction, and there were no significant differences between them regarding these parameters. The 2,3 DPG levels were slightly reduced in both groups. CONCLUSIONS: This study shows that patients who are massively transfused following cardiovascular surgery present cell oxygenation disturbances probably as a result of O2 transport inadequacy.


Assuntos
Transfusão de Sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Consumo de Oxigênio , Choque Hemorrágico/terapia , 2,3-Difosfoglicerato/sangue , Análise de Variância , Gasometria , Hemodinâmica , Humanos , Ácido Láctico/sangue , Oxigênio/sangue , Complicações Pós-Operatórias , Estudos Prospectivos , Choque Hemorrágico/etiologia , Fatores de Tempo
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