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1.
Epidemiol Infect ; 145(8): 1658-1669, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28325171

RESUMO

The primary study objective was to investigate three decades from 1985 to 2014 of changes in pregnancies among HIV-infected women. The secondary objective was to assess risk factors associated with preterm delivery and severe small-for-gestational-age (SGA) infants in HIV-infected women. A retrospective review of deliveries among pregnant HIV-infected women at the University of Genoa and IRCCS San Martino-IST in Genoa between 1985 and 2014 was performed. Univariate and multivariable analyses were used to study the variables associated with neonatal outcomes. Overall, 262 deliveries were included in the study. An increase in median age (26 years in 1985-1994 vs. 34 years in 2005-2014), in the proportion of foreigners (none in 1985-1994 vs. 27/70 (38·6%) in 2005-2014), and a decrease in intravenous drug use (75·2% (91/121) in 1985-1994 vs. 12·9% (9/70) in 2005-2014) among pregnant HIV-infected women was observed. Progressively, HIV infections were diagnosed sooner (prior to pregnancy in 80% (56/70) of women in the last decade). An increase in combined antiretroviral therapy (cART) prescription during pregnancy (50% (27/54) in 1995-2004 vs. 92·2% (59/64) in 2005-2014) and in HIV-RNA <50 copies/ml at delivery (19·2% (5/26) in 1995-2004 vs. 82·3% (53/64) in 2005-2014) was observed. The rate of elective caesarean section from 1985 to 1994 was 9·1%, which increased to 92·3% from 2004 to 2015. Twelve (10·1%) mother-to-child transmissions (MTCT) occurred in the first decade, and six (8·3%) cases occurred in the second decade, the last of which was in 2000. Preterm delivery (<37 weeks gestation) was 5% (6/121) from 1985 to 1994 and increased to 17·1% (12/70) from 2005 to 2014. In univariate and multivariable logistic regression analyses, advancing maternal age and previous pregnancies were associated with preterm delivery (odds ratio (OR) 2·7; 95% confidence intervals (CI) 1-7·8 and OR 2·6; 95% CI 1·1-6·7, respectively). In the logistic regression analysis, use of heroin or methadone was found to be the only risk factor for severe SGA (OR 3·1; 95% CI 1·4-6·8). In conclusion, significant changes in demographic, clinical and therapeutic characteristics of HIV-infected pregnant women have occurred over the last 30 years. Since 2000, MTCT has decreased to zero. An increased risk of preterm delivery was found to be associated with advancing maternal age and previous pregnancies but not with cART. The use of heroin or methadone has been confirmed as a risk factor associated with severe SGA.


Assuntos
Infecções por HIV/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Complicações Infecciosas na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , Feminino , Infecções por HIV/complicações , Humanos , Recém-Nascido , Itália/epidemiologia , Estudos Longitudinais , Gravidez , Nascimento Prematuro/etiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
2.
Clin Exp Immunol ; 158(1): 55-63, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19737231

RESUMO

Anti-retroviral treatment (ART) usually results in efficient control of virus replication and in immune reconstitution. Among potential adverse effects, impairment of immune responses in terms of CD4(+) T cell counts has been attributed to some ART regimens, as with didanosine-tenofovir. We studied the functional integrity of adaptive and innate immunity during didanosine-tenofovir-containing ART. Two groups of extensively pretreated patients completing at least 48 weeks of ART containing either lamivudine-didanosine (n = 21) or tenofovir-didanosine (n = 25) were identified. In addition to standard clinical immune and virological parameters, we performed a flow cytometric analysis of natural killer (NK) cells, of memory and naive CD4(+) T cells and of T cell receptor alphabeta(+) T cells co-expressing inhibitory NK receptors. Functional analysis consisted in specific and total interferon-gamma production by NK cells and of recall antigen proliferation of peripheral blood mononuclear cells. Comparable clinical immunological reconstitution and virological control were confirmed in the two groups of patients in the absence of clinically relevant adverse effects. The proportion of CD4(+)CD45RA(+) T cells and of functionally inhibited killer immunoglobulin-like receptor T cell receptor alphabeta(+) cells, the proliferation to recall antigens as well as NK cell phenotype and function as determined by interferon-gamma production in patients treated with tenofovir-didanosine were comparable to those treated with a different regimen. Thus, no differences in functional innate or adaptive immune reconstitution are detected in drug-experienced human immunodeficiency virus-infected patients on tenofovir-didanosine nucleoside reverse transcription inhibitor regimens.


Assuntos
Adenina/análogos & derivados , Didanosina/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Organofosfonatos/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Linfócitos T/imunologia , Adenina/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Proliferação de Células , Quimioterapia Combinada , Citometria de Fluxo , Imunofluorescência , Seguimentos , Infecções por HIV/imunologia , Humanos , Memória Imunológica , Imunofenotipagem , Interferon gama/imunologia , Células Matadoras Naturais/imunologia , Lamivudina/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Tenofovir
3.
Clin Exp Dermatol ; 34(8): e623-5, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19489851

RESUMO

We describe a 23-year-old patient who presented acutely with haemophagocytic lymphohistiocytosis (HL) and Melkersson-Rosenthal syndrome (MRS). MRS and HL are two unusual and complex clinical patterns that may present acutely and to our knowledge, an association between them has never been reported. The clinical investigations in this patient led to identification of parvovirus B19 (PB19) viraemia by PCR. Parvovirus infection has been reported as a cause of virus-associated HL, but the presence of PB19 has never been sought or reported as a possible trigger for MRS. This observation suggests a possible association between PB19 and HL, and opens the possibility of its association also with acute-onset MRS. Further investigations for the presence of PB19 in cases of MRS are warranted.


Assuntos
Linfo-Histiocitose Hemofagocítica/patologia , Síndrome de Melkersson-Rosenthal/patologia , Infecções por Parvoviridae/patologia , Parvovirus B19 Humano , Evolução Fatal , Humanos , Linfo-Histiocitose Hemofagocítica/imunologia , Masculino , Síndrome de Melkersson-Rosenthal/imunologia , Infecções por Parvoviridae/imunologia , Parvovirus B19 Humano/imunologia , Índice de Gravidade de Doença , Viremia/diagnóstico , Viremia/virologia , Adulto Jovem
4.
Biomed Pharmacother ; 97: 1575-1585, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29793320

RESUMO

Mimosa tenuiflora (Willd.) Poiret, popularly known in Brazil as "jurema-preta" is widely used against bronchitis, fever, headache and inflammation. Its antioxidant, anti-inflammatory and antinociceptive potential has already been reported. To assess the orofacial antinociceptive effect of M. tenuiflora, ethanolic extracts of M. tenuiflora (leaves, twigs, barks and roots) were submitted to in vitro tests of antioxidant activity. The extract with the highest antioxidant potential was partitioned and subjected to preliminary chemical prospecting, GC-MS, measurement of phenolic content and cytotoxicity tests of the fraction with the highest antioxidant activity. The nontoxic fraction with the highest antioxidant activity (FATEM) was subjected to tests of acute and chronic orofacial nociception and locomotor activity. The possible mechanisms of neuromodulation were also assessed. The EtOAc fraction, obtained from the ethanolic extract of M. tenuiflora barks, was the one with the highest antioxidant potential and nontoxic (FATEM), and Benzyloxyamine was the major constituent (34.27%). FATEM did not alter the locomotor system of mice and reduced significantly the orofacial nociceptive behavior induced by formalin, glutamate, capsaicin, cinnamaldehyde or acidic saline compared to the control group. FATEM also inhibited formalin- or mustard oil-induced temporomandibular nociception. In addition, it also reduced mustard oil-induced orofacial muscle nociception. However, FATEM did not alter hypertonic saline-induced corneal nociception. Neuropathic nociception was reversed by treatment with FATEM. The antinociceptive effect of FATEM was inhibited by naloxone, L-NAME and glibenclamide. FATEM has pharmacological potential for the treatment of acute and neuropathic orofacial pain and this effect is modulated by the opioid system, nitric oxide and ATP-sensitive potassium channels. These results lead us to studies of isolation and characterization of bioactive principles.


Assuntos
Analgésicos/uso terapêutico , Dor Facial/tratamento farmacológico , Mimosa/química , Nociceptividade , Extratos Vegetais/uso terapêutico , Acroleína/análogos & derivados , Analgésicos/farmacologia , Animais , Antioxidantes/metabolismo , Capsaicina , Fracionamento Químico , Chlorocebus aethiops , Etanol , Dor Facial/patologia , Ácido Glutâmico , Glibureto/farmacologia , Glibureto/uso terapêutico , Camundongos , Atividade Motora/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , NG-Nitroarginina Metil Éster/uso terapêutico , Naloxona/farmacologia , Naloxona/uso terapêutico , Nociceptividade/efeitos dos fármacos , Fenóis/análise , Extratos Vegetais/farmacologia , Ratos Wistar , Articulação Temporomandibular/efeitos dos fármacos , Articulação Temporomandibular/patologia , Células Vero
5.
J Chemother ; 19(3): 335-8, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17594931

RESUMO

Primary treatment failure and mortality in non-neutropenic patients with candidemia is high according to clinical trial experience. Current guidelines are mainly useful only for first line treatment strategies.We describe treatment failure and persistent protracted Candida albicans candidemia without clinically evident ocular involvement nor catheter recolonization in a malnourished non-neutropenic surgical patient with peritonitis. Primary antifungal treatment failure with fluconazole and secondary treatment failure with caspofungin occurred in the absence of evident Candida seeding the eye, valvular endocardium, or the intravascular catheter. Switch to liposomal amphotericin B was followed by clinical and microbiological cure. In patients with multiple risk factors for the acquisition of candidemia and life-threatening clinical conditions, the possibility of primary/secondary failure of new potent antifungal regimens may be initially neglected. Additional multicenter controlled clinical data are needed to guide the timing and choice of secondary antifungal treatment regimens in non-neutropenic candidemia patients.


Assuntos
Antifúngicos/uso terapêutico , Candida albicans , Fungemia/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Anfotericina B/uso terapêutico , Caspofungina , Combinação de Medicamentos , Equinocandinas , Feminino , Fluconazol/uso terapêutico , Humanos , Ileostomia , Lipopeptídeos , Pessoa de Meia-Idade , Peptídeos Cíclicos/uso terapêutico , Fosfatidilcolinas/uso terapêutico , Fosfatidilgliceróis/uso terapêutico , Guias de Prática Clínica como Assunto
6.
Chem Biol Interact ; 256: 9-15, 2016 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-27302204

RESUMO

Orofacial pain is a highly prevalent clinical condition, yet difficult to control effectively with available drugs. Much attention is currently focused on the anti-inflammatory and antinociceptive properties of lectins. The purpose of this study was to evaluate the antinociceptive effect of frutalin (FTL) using rodent models of inflammatory and neuropathic orofacial pain. Acute pain was induced by formalin, glutamate or capsaicin (orofacial model) and hypertonic saline (corneal model). In one experiment, animals were pretreated with l-NAME and naloxone to investigate the mechanism of antinociception. The involvement of the lectin domain in the antinociceptive effect of FTL was verified by allowing the lectin to bind to its specific ligand. In another experiment, animals pretreated with FTL or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to infraorbital nerve transection to induce chronic pain, followed by induction of thermal hypersensitivity using acetone. Motor activity was evaluated with the rotarod test. A molecular docking was performed using the TRPV1 channel. Pretreatment with FTL significantly reduced nociceptive behaviour associated with acute and neuropathic pain, especially at 0.5 mg/kg. Antinociception was effectively inhibited by l-NAME and d-galactose. In line with in vivo experiments, docking studies indicated that FTL may interact with TRPV1. Our results confirm the potential pharmacological relevance of FTL as an inhibitor of orofacial nociception in acute and chronic pain mediated by TRPA1, TRPV1 and TRPM8 receptor.


Assuntos
Analgésicos/uso terapêutico , Dor Facial/tratamento farmacológico , Galectinas/uso terapêutico , Dor Aguda/tratamento farmacológico , Dor Aguda/metabolismo , Analgésicos/isolamento & purificação , Animais , Artocarpus/química , Modelos Animais de Doenças , Dor Facial/metabolismo , Galectinas/isolamento & purificação , Camundongos , Simulação de Acoplamento Molecular , Neuralgia , Ratos Wistar , Canais de Cátion TRPM/metabolismo , Canais de Cátion TRPV/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo
7.
Cell Death Differ ; 2(1): 47-56, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17180015

RESUMO

Fibre cells in the ocular lens exhibit a constitutive apoptotic process of nuclear degradation that includes chromatin breakage, generating a ladder pattern of DNA fragments. This process is intrinsic to the normal terminal differentiation program. Despite the loss of nucleus and cytoplasmic organelles, the terminal differentiated fibre cells remain in the lens during the whole life span of the individual. The lens cells thus provide a unique system in which to determine the presence and fate of endonucleases once the chromatin has been cleaved. We report here on the presence of DNase activity in nucleated and anucleated lens cells. Using a nuclease gel assay and double-stranded DNA as substrate, we found active 30 and 60 kDa DNases. The enzymatic activities were Ca(2+), Mg(2+) dependent, and active at neutral pH. The relative amount of these forms changed during development and aging of the lens fibre cells. Both forms were inhibited by Zn(2+), aurintricarboxylic acid, and G-actin. The proteins were also separated by SDS-PAGE, renatured after removing SDS and incubated in the presence of native DNA adsorbed to a membrane. Therefore it was possible to demonstrate, by means of a nick translation reaction, that the enzymes produced single strand cuts. Based on these findings we propose that these chick lens nucleases are probably related to DNase I.

8.
AIDS ; 15(8): 965-74, 2001 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-11399978

RESUMO

BACKGROUND: Highly active antiretroviral therapy (HAART) is associated with a decrease in viral replication to undetectable levels and with an increase in CD4 T lymphocytes. Residual HIV-1 replication occurs together with incomplete recovery of cytotoxic CD8 T lymphocyte (CTL) numbers and function. We sought to determine whether expression of HLA class I-specific inhibitory natural killer receptors (iNKR) on the CTL of patients who had been treated successfully with HAART for 24 months could be involved, at least in part, in residual CTL functional inhibition. METHODS: Two-colour cytofluorometry was used to analyse the expression of six different iNKR including p58.1, p58.2, p70, p140, CD94/NKG2A and LIR1/ILT2 on the CD3, CD8 lymphocytes of eight patients with successful long-term suppression of viral replication before and after 3, 6 and 24 months of HAART. Healthy subjects were analysed as controls. HIV-1-specific cytotoxic activity was determined after 24 months of HAART in the presence and absence of iNKR-masking. RESULTS: No significant reduction of iNKR expression on CD8 T cells was observed by 6 months. Expression of p70 and p140 was inversely correlated with the increasing CD4 numbers. After 24 months CD8 T-lymphocytes expressing p58.1, p58.2, p70, p140 and CD94/NKG2A returned to levels indistinguishable from those of the healthy controls. A significantly increased proportion of CD8 CTL still expressed LIR1/ILT2, a receptor with broad HLA-class I specificity. Functional analysis of freshly separated cells revealed that the disruption of the interaction between LIR1/ILT2 and HLA-class I could partly restore HIV-1-specific lysis. CONCLUSIONS: A decrease in CD3CD8iNKR cells is observed beyond 6 months of HAART. In some patients functional impairment due to LIR1/ILT2 expression may persist even after 24 months of successful HAART.


Assuntos
Antígenos CD , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD8-Positivos/metabolismo , Infecções por HIV/imunologia , HIV-1/imunologia , Células Matadoras Naturais/metabolismo , Receptores Imunológicos/metabolismo , Adulto , Feminino , Citometria de Fluxo , Imunofluorescência , Infecções por HIV/tratamento farmacológico , Humanos , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Masculino , Pessoa de Meia-Idade , Subfamília C de Receptores Semelhantes a Lectina de Células NK , Receptores KIR , Receptores KIR2DL3 , Receptores de Células Matadoras Naturais , Linfócitos T Citotóxicos/metabolismo , Fatores de Tempo , Replicação Viral
9.
AIDS ; 14(10): 1421-8, 2000 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-10930158

RESUMO

OBJECTIVE: To determine whether mode of delivery or the use of maternal or neonatal antiretroviral prophylaxis influence the age when HIV-1 can first be detected in infected infants, particularly the probability of detection at birth. METHODS: In a collaboration between four multicentre studies, data on 422 HIV-1 infected infants who were assessed by HIV-1 DNA PCR or cell culture before 14 days of age were analysed. Weibull mixture models were used to estimate the cumulative proportion of infants with detectable levels of HIV-1 according to use of maternal/neonatal antiretroviral therapy (mainly zidovudine monotherapy) and mode of delivery. RESULTS: HIV-1 was detected in 162 infants (38%) when they were first tested, at a median age of 2 days. At birth, it was estimated that 36% [95% confidence interval (CI), 31-41%] of infants have levels of virus that can be detected by DNA PCR or cell culture. This percentage was not associated with either mode of delivery (35% for vaginal delivery versus 40% for cesarean section delivery; P = 0.4) or the use of maternal or neonatal antiretroviral prophylaxis. Among infants with undetectable levels of HIV-1 at birth, the median time to viral detectability was estimated to be 14.8 days (95% CI, 12.9-16.8 days). This time was increased by 15% (95% CI, -11 to 48%; P = 0.3) among infants who were exposed to antiretroviral therapy postnatally compared with infants who were not exposed. No effect was observed for mode of delivery. CONCLUSIONS: The outcome of an early virological test for HIV-1 is thought to be related directly to the timing of transmission and cesarean section delivery primarily reduces the risk of intrapartum transmission. The absence of an association between mode of delivery and viral detectability at birth was therefore unexpected. There was no evidence that foetal or neonatal exposure to prophylactic zidovudine delays substantially the diagnosis of infection, although this cannot be inferred for combination antiretroviral therapy.


Assuntos
Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez , Fatores Etários , Fármacos Anti-HIV/uso terapêutico , Cesárea , Feminino , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Prospectivos , Zidovudina/uso terapêutico
10.
J Clin Endocrinol Metab ; 61(2): 378-81, 1985 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-4008612

RESUMO

The effect of benserazide administration on the secretion of GH, PRL, and TSH has been considered as an index of dopamine regulatory actions. Nine acromegalic patients and nine normal subjects were given a single 125 mg oral dose of benserazide, and serum GH, PRL, and TSH were determined by RIA methods every 30 min for 4 h. Benserazide did not alter GH values either in normal subjects or in acromegalic patients. A significant increase of serum PRL was found in both groups, and the increase was similar in normoprolactinemic and in hyperprolactinemic acromegalic patients. A significant increase in TSH levels was found only in acromegalic patients. Thus, a decrease in dopamine outside the blood-brain barrier did not affect GH secretion, whereas PRL secretion was changed in the acromegalic as well as in the control group.


Assuntos
Acromegalia/sangue , Benserazida/farmacologia , Hormônio do Crescimento/sangue , Hidrazinas/farmacologia , Prolactina/sangue , Tireotropina/sangue , Adulto , Dopamina/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Gene ; 163(1): 163-4, 1995 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-7557471

RESUMO

We have cloned, from Dictyostelium discoideum, a cDNA encoding a new heat-shock (HS) protein (Hsp) with a predicted molecular mass of 31,447 Da. Outside of its low molecular mass, this Hsp does not share any similarity with the small Hsp currently identified or with alpha-crystallins. Northern blot analysis indicates that this HS-inducible gene is also developmentally regulated

.


Assuntos
Dictyostelium/metabolismo , Proteínas de Choque Térmico/biossíntese , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Sequência Conservada , Cristalinas/química , DNA Complementar , Dictyostelium/genética , Regulação Fúngica da Expressão Gênica , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/genética , Dados de Sequência Molecular , Peso Molecular , Fases de Leitura Aberta , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Homologia de Sequência de Aminoácidos
12.
J Acquir Immune Defic Syndr (1988) ; 6(4): 376-9, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8455142

RESUMO

Zidovudine (ZDV) administration during pregnancy has been suggested for the prevention of mother-to-child HIV-1 transmission. Reliable levels of the drug have been observed in the fetus and in the newborn. Seven HIV-1-infected pregnant women who declined to have abortions and whose immunological status required antiretroviral treatment were administered oral ZDV 18 mg/kg in four daily doses, the initial dose being administered anytime from the 16th to the 30th week of gestation up until the time of delivery. Follow-up of the seven infants from birth with a mean duration of 22 months (range 16-32 months) revealed mild drug-related toxicity: anemia in two infants and macrocytosis in all seven, both conditions resolved by the second month of life. All infants remained HIV-1 seronegative, according to the 1987 CDC classification, and all stayed clinically well. Other virological parameters including virus culture, in vitro antibody production, and polymerase chain reaction, repeatedly performed in the infants, remained negative. Although none of the mothers transmitted HIV-1 infection to the offspring, the size of this study and the relatively low transmission rate (13%) in Europe do not permit us to draw a definite conclusion about treatment efficacy in preventing maternal-fetal transmission. However, the drug caused only limited toxicity among the infants, and its administration to large numbers of mothers in treatment trials should be considered relatively safe for both mother and child.


Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1 , Recém-Nascido , Complicações Infecciosas na Gravidez , Zidovudina/uso terapêutico , Feminino , Infecções por HIV/transmissão , Humanos , Gravidez , Zidovudina/efeitos adversos
13.
Am J Med ; 75(1B): 7-18, 1983 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-6349346

RESUMO

Despite the frequency and importance of both nosocomial and "community-acquired" bacteremia, definitive information concerning crucial pathophysiologic events in human bacteremia remains sparse. An extensive variety of clinical manifestations, such as fever, rigors, shock, altered circulatory dynamics, cutaneous manifestations changes in the coagulation, complement, and other mediator systems, and effects on the lungs, heart, kidney, liver, and other end organs, have been described, but it is difficult to determine the relative frequency of these events in bacteremia caused by different species. The extensive number of bacterial species capable of producing bacteremia and variations in the type of presentation, such as acute, asymptomatic, and chronic, even when bacteremia is produced by the same species, undoubtedly contribute to this difficulty and suggest that a variety of pathophysiologic mechanisms occur in various bacteremias. In contrast, the relative frequency of various manifestations and some pathophysiologic mechanisms have been better delineated in Gram-negative bacteremia. The development of bacteremia enhances the lethality of most types of localized infection and several studies have demonstrated a relation between the magnitude of bacteremia and the outcome of the disease. Among various pathophysiologic alterations, mechanisms involved in the production of fever have been delineated most clearly. Fever appears to reflect a "common pathway" with almost all infectious agents and results from release of endogenous pyrogen from phagocytic cells. Endogenous pyrogen regulates the thermostatic setting of the body through its effect on the anterior hypothalamus. Endogenous pyrogen seems identical with Interleukin 1 and exerts a variety of other biologic activities. An extensive number of bacterial components have been proposed as "effectors" and an equally large number of endogenous substances proposed as "mediators" of the pathophysiologic events in bacteremia. The importance of many of these effectors and mediators has been postulated largely on the basis of in vitro and animal studies. The lack of critical clinical studies hampers extrapolation of these experimental studies to human bacteremia. The development of more effective therapy for the complications of bacteremia, such as shock, will continue to be hampered until the mechanisms involved in the production of those pathophysiologic events that are crucial determinants of outcome have been delineated more precisely in human disease.


Assuntos
Sepse/fisiopatologia , Toxinas Bacterianas/farmacologia , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/etiologia , Ativação do Complemento , Coagulação Intravascular Disseminada/etiologia , Endorfinas/fisiologia , Endotoxinas/farmacologia , Febre/etiologia , Cardiopatias/etiologia , Humanos , Nefropatias/etiologia , Fígado/fisiopatologia , Prostaglandinas/fisiologia , Pirogênios/biossíntese , Síndrome do Desconforto Respiratório/etiologia , Estremecimento , Choque Séptico/etiologia , Manifestações Cutâneas
14.
Immunol Lett ; 72(3): 179-82, 2000 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10880839

RESUMO

Several mechanisms may contribute to the decline in HIV-1 specific CD8+ cytotoxic T-lymphocyte (CTL) activity that is observed in infected patients, including loss of CD4+ cell help, antigenic shift, impaired clonogenicity and functional impairment due to expression of inhibitory NK receptors (iNKRs). In addition to a decrease in HIV-1-specific cytolytic activity, an increased proportion of CD8+ T-cells producing IL-4 and IL-5 has been recently observed in advanced HIV-1 infection. Remarkably, an impaired HIV-1-specific CTL activity was primarily detected among the TC0/Tc2 CD8+ CTLs. A series of CD3+CD8+ T-cell clones expressing inhibitory NK receptors (iNKRs) isolated from HIV-1 infected patients was analyzed in order to determine their cytokine production pattern and to assess the extent of iNKR expression at the single cell level. Our data indicate that iNKR+CD3+CD8+ clones isolated from infected patients frequently express multiple iNKR and may produce IL-4 and IL-5 to a relevant extent.


Assuntos
Antígenos CD/biossíntese , Infecções por HIV/imunologia , HIV-1/imunologia , Interleucina-4/biossíntese , Interleucina-5/biossíntese , Lectinas Tipo C , Glicoproteínas de Membrana/biossíntese , Receptores Imunológicos/biossíntese , Linfócitos T Citotóxicos/imunologia , Infecções por HIV/sangue , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Subfamília D de Receptores Semelhantes a Lectina de Células NK , Receptores KIR , Receptores de Células Matadoras Naturais
15.
Am J Cardiol ; 60(11): 67F-72F, 1987 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-3310588

RESUMO

Moricizine HCl, an antiarrhythmic phenothiazine drug, was investigated for its efficacy against ventricular tachycardia (VT) in a group of 60 patients from 8 institutions using electrophysiologic testing before and after oral administration. Moricizine HCl significantly prolonged PR, QRS, AH and HV intervals and cycle length for atrioventricular nodal block, but had minimal or no effect on repolarization or cardiac refractory periods. Induction of sustained VT (in 33 patients) and nonsustained VT (in 14 patients) occurred at baseline. During moricizine HCl therapy, sustained VT was induced in 31 patients and nonsustained VT in 7 patients. In individual patients, suppression of VT induction was obtained in 18% of patients with sustained VT and in 27% of patients with nonsustained VT. Cycle length of induced VT was significantly prolonged by moricizine HCl therapy. During prospective follow-up of 37 patients, electrophysiologic study predicted recurrence of nonrecurrence of VT with a sensitivity value of 82% and specificity of 65%.


Assuntos
Antiarrítmicos/uso terapêutico , Fenotiazinas/uso terapêutico , Taquicardia/fisiopatologia , Fibrilação Ventricular/fisiopatologia , Adulto , Idoso , Estimulação Cardíaca Artificial , Estimulação Elétrica , Eletrofisiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Moricizina , Recidiva , Período Refratário Eletrofisiológico , Taquicardia/tratamento farmacológico , Fibrilação Ventricular/tratamento farmacológico
16.
Hum Immunol ; 61(1): 74-81, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10658980

RESUMO

One of the most characteristic and, at the same time, puzzling features of the cellular immune response towards HIV-1 is represented by an early vigorous HIV-specific CD8+ CTL response that does not prevent disease progression in the vast majority of patients. In this context, there is a striking mismatch over the course of disease progression between increasing numbers of activated CD8+ T cells and apparent decrease of virus-specific CD8+ CTLs. Inhibitory NK receptors (iNKRs) specific for HLA class I molecules can be expressed on CD8+ T-cells of healthy individuals and deliver inhibitory signals that determine decreased CTL function. Their expression on CD8+ CTL may be induced by IL-15 or TGFP in vitro, and may represent an important regulatory function for the fine-tuning of the antigen-specific T cell response against tumors and intracytoplasmic pathogens. In HIV-1 infected patients, relevant proportions of peripheral blood CD8+ T lymphocytes express iNKRs belonging to the Ig superfamily (p58/p70/p140) and CD94/NKG2A. Presence of iNKRs on CD8+ CTLs impairs HIV-1-specific cytolytic activity in vitro and may allow uncontrolled viral replication and spread following functional inhibition of CTL effectors in infected patients.


Assuntos
Infecções por HIV/imunologia , HIV-1/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Células Matadoras Naturais/imunologia , Receptores Imunológicos/metabolismo , Linfócitos T Citotóxicos/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Receptores Imunológicos/imunologia , Receptores KIR , Receptores KIR2DL3
17.
AIDS Res Hum Retroviruses ; 4(2): 131-6, 1988 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3284554

RESUMO

The suitability of collecting whole blood specimens on filter paper disks for HIV antibody assay was evaluated. ELISA and Western blot assay results were in complete agreement for serum and blood spot disk samples. Sensitivity of the two methods was tested using diluted whole blood and sera from HIV-seropositive individuals. Results demonstrate that ELISA and Western blot assays performed on punched-out disks of the blood-impregnated papers had the same sensitivities as those obtained with serum samples. This study suggests that whole blood collection on filter paper can be effectively substituted for serum sampling in HIV antibody screening programs.


Assuntos
Anticorpos Antivirais/análise , Coleta de Amostras Sanguíneas/métodos , Soropositividade para HIV/diagnóstico , Coleta de Amostras Sanguíneas/instrumentação , Criança , Ensaio de Imunoadsorção Enzimática , HIV/imunologia , Anticorpos Anti-HIV , Humanos , Sensibilidade e Especificidade
18.
AIDS Res Hum Retroviruses ; 10(6): 675-82, 1994 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8074931

RESUMO

The susceptibility of normal human tonsillar stromal cells (HTSCs) to infection by HIV-1 was assessed using transmission electron microscopy (TEM), immunocytochemistry, and HIV-1-specific PCR analyses. Our results demonstrate that HTSCs are efficiently infected following cocultivation with the HIV-1-infected lymphoblastoid cell line GY1. Infected stromal cells contain intracellular viral particles present as free virus or associated with phagocytic vesicles. These particles express the HIV-1-specific p24 antigen as assessed by immunocytochemical analyses using an HIV-specific anti-p24 monoclonal antibody. Moreover, PCR analysis of genomic DNA isolated from particle-bearing tonsillar stromal cells identified HIV-1-specific sequences not present in either uninfected stromal cells or parental GY1 uninfected cells. The mechanism by which HIV-1 infects HTSCs does not appear to be CD4 mediated, as none of the human tonsillar stromal cell lines express CD4 as assessed by flow cytometry, immunohistochemistry, and PCR analysis. Taken together, these results demonstrate that human tonsillar stromal cells can be infected by HIV-1, and that subsequent to infection the viral genome is reverse transcribed, and integrated into the stromal cell DNA. The infection of HTSCs may contribute to HIV-1-mediated pathogenesis indirectly as a viral reservoir or directly by structural and functional modification of the lymphoid microenvironment.


Assuntos
Linfócitos B/microbiologia , Infecções por HIV/transmissão , Tonsila Palatina/microbiologia , Anticorpos Monoclonais , Linfócitos B/ultraestrutura , Linhagem Celular , Genes gag , HIV-1/genética , HIV-1/imunologia , HIV-1/ultraestrutura , Humanos , Tonsila Palatina/ultraestrutura , Reação em Cadeia da Polimerase , Células Estromais/microbiologia , Células Estromais/ultraestrutura
19.
Pediatr Infect Dis J ; 9(1): 26-30, 1990 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2405347

RESUMO

In children born to mothers infected with human immunodeficiency virus 1 (HIV-1), a diagnosis of HIV infection cannot be based on a positive antibody result until at least 18 months of age. There is therefore an urgent need for simple and reliable methods of diagnosing HIV infection in these infants. The sensitivity and specificity of a test using the in vitro antibody production of HIV-specific IgG was assessed in children whose infection status was known and compared with virus and antigen detection. In vitro antibody production sensitivity was 90 to 95%, at least as sensitive as virus culture in antibody-positive infected children. In the first 2 months there is a relatively high proportion of false positive results, possibly a result of contamination by maternal cells. However, after this period in vitro antibody production is a simple, inexpensive and reliable tool for early diagnosis.


Assuntos
Anticorpos Anti-HIV/biossíntese , Infecções por HIV/diagnóstico , HIV-1/imunologia , Imunoglobulina G/biossíntese , Linfócitos/imunologia , Complexo Relacionado com a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Células Cultivadas , Pré-Escolar , Reações Falso-Positivas , Antígenos HIV/análise , HIV-1/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Estudos Multicêntricos como Assunto , Valor Preditivo dos Testes
20.
DNA Cell Biol ; 17(7): 635-41, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9703022

RESUMO

Hsp32 is a heat shock gene in D. discoideum. We have previously observed that heat stress-induced change produces a broad band on Northern blots, suggesting that more than one population of mRNA is present under those conditions. This was not the result of a defect in the splicing of the hsp32 mRNA, nor did it result from the use of a different transcription start site under heat shock conditions. Here, we show that the broad banding pattern reflects the appearance of a transcript with a poly(A) tail that is approximately 100 nt longer than that seen in unstressed cells. Experiments indicated that this tail was not a property of newly synthesized mRNA but rather a response to heat stress. This response appeared to be specific to the hsp32 transcript and did not result in the retention of the RNA in the nucleus. These results document a relatively unusual heat shock response and also indicate that the nature of the response differs among RNAs and has selective consequences.


Assuntos
Dictyostelium/genética , Proteínas de Choque Térmico/genética , Resposta ao Choque Térmico/genética , Poli A/metabolismo , Proteínas de Protozoários , RNA/metabolismo , Animais , Meios de Cultura/farmacologia , Dictyostelium/química , Dictyostelium/metabolismo , Células Eucarióticas/citologia , Células Eucarióticas/efeitos dos fármacos , Células Eucarióticas/metabolismo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico/efeitos dos fármacos , Poli A/genética , RNA/efeitos dos fármacos , RNA/genética , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Temperatura , Fatores de Tempo
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