Anti-HIV-1 seroreactivity and HIV transmission route[R1]. The HEC/FIOCRUZ AIDS Clinical Research Group.

BACKGROUND: Antibody binding assays carried out by our group have consistently indicated a higher reactivity of sera from male HIV-1 infected individuals. This study was carried out in order to analyze the importance of gender, route of transmission, disease progression and HIV-1 genotype in seroreactivity assays. STUDY DESIGN: Specificity of antibody binding was studied in plasma of 247 HIV-1 seropositive individuals belonging to patient groups of pregnant women, injecting drug users (IDUs) and recent seroconvertors, resident in Rio de Janeiro, RJ. Recognition of synthetic peptides corresponding to antigenically important epitopes in the envelope of HIV-1 (gp41 immunodominant epitope, V3 loop, V2 loop and gp41 735-752 epitope) was determined. RESULTS: The immunodominant gp41 peptide (amino acids 594-613, HIV-1 MN sequence) was recognized by 85% of all plasma tested. Reactivity with the gp41 735-752 peptide and gp120 V2 loop peptides was low but quite variable, being generally more often specific to a Brazilian V2 peptide used than to the HIV-1 MN derived V2 peptide. The overall recognition of the different V3 peptides tested varied from 41 to 76%. Patients with more advanced disease showed a more frequent reactivity with the peptides studied than did asymptomatic patients. Statistically significant differences in peptide recognition were observed by multiple logistic analyses comparing plasma derived from individuals infected by blood or sexual HIV transmission, adjusting for disease progression and gender. Plasma from individuals infected by sexual transmission showed lower peptide recognition than did plasma from individuals infected through HIV positive blood. Association attempts between seroreactivity and genotype indicated that plasma derived from patients infected with HIV-1 of the F subtype showed highest recognition of heterologous V3 peptides, as well as a slightly more frequent recognition of the non-V3 peptides tested. Recognition of homologous peptides was generally higher than recognition of heterologous peptides. Differences were most pronounced between the prototypical HIV-1 B subtype and the Brazilian B" variant of this subtype but almost non-existent between the HIV-1 B and F subtypes. CONCLUSIONS: Individual gender was shown to be a confounder when investigating the relationships of peptide reaction to HIV-1 route of transmission through multivariate statistical methods: patients infected by blood transmission (IDU) present higher frequency of peptide recognition than individuals infected by sexual HIV-1 transmission. Plasma from individuals infected with the B" variant (GWG) of B subtype HIV-1 showed lower heterologous peptide recognition than that from HIV-1 B (GPG) or F infected individuals.     

Rhesus differential susceptibility to endotoxin is not associated with activation of plasma prekallikrein

This study is part of a project aimed at understanding individual responses to acute endotoxemia in a catheter-free rhesus (Macaca mulatta) model of inflammation. In the previous study [J. Endotoxin Res. 2 (1995) 411-420.], we showed that of 14 endotoxin 0111:B4 (ETX)-infused monkeys, only three died at < 13.5 h and one at 6 days postinfusion. Doses of ETX correlated neither with the magnitude of hypotension nor with rhesus outcome. Survival (and death at 6 days) or death at < 13.5 h was rather associated with controllable or uncontrollable rise of plasma levels of proinflammatory cytokines and reversible or irreversible shock. In the current study, we used plasmas of 5 survivors and of one of the monkeys that died at < 13.5 h (each infused with 3 X 10(6) EU ETX/kg), and of two saline control monkeys of the previous study. We analyzed changes in parameters of coagulation and contact systems. After ETX infusion, activated partial thromboplastin time (APTT) and prothrombin time (PT) values increased modestly in survivors but markedly in the nonsurvivor; responses of platelet counts and levels of fibrinogen, antithrombin, alpha2-macroglobulin (alpha2M), Cl-inhibitor (C1INH) and alpha1 -antitrypsin were similar in survivors and the nonsurvivor; the rate of plasma prekallikrein (PK) activation measured by hydrolysis of the kallikrein (KAL) substrate D-Pro-Phe-Arg-p-nitroanilide was not altered by ETX infusion; and the distribution of PK activation products, analyzed by MAb 13G11/immunoblotting in plasmas with or without artificial activation, was similar in survivors and the nonsurvivor. Responses in controls were relatively stable. Since we used defined experimental conditions, this primate model has the potential to be useful to study further correlation of inflammatory parameters with differential outcome.     

Prenatal maternal stress is associated with delivery analgesia and unplanned cesareans

We tested the hypothesis that women with greater prenatal maternal stress (PNMS) would be more likely to receive intravenous opiates and epidural for delivery, and thereby increase the likelihood of unplanned cesarean delivery. PNMS was assessed during early, mid, and late pregnancy using psychometrically sound instruments in structured interviews with women receiving prenatal care at a public university clinic. Medical records were abstracted for analgesia during delivery, fetal heart tracing (FHT) abnormalities, and method of delivery. Only subjects attempting vaginal delivery (N = 298) were included. Using structural equation modeling, a PNMS variable was constructed from five indicators: pregnancy-specific distress, number of prenatal stressful life events, distress from life events, state anxiety, and perceived stress. After controlling for medical predictors of analgesia receipt and surgical delivery, women with higher PNMS were more likely to receive analgesia, and those who received analgesia were more likely to deliver surgically. Analgesia was also associated with FHT abnormalities, which in turn was associated with surgical delivery (all p's < 0.05). Women who received both an epidural and meperidine were most likely to have a cesarean delivery; 29% of this group delivered surgically. Results indicate that PNMS contributes to higher likelihood of unplanned cesarean delivery through its association with delivery analgesia.     

Endomiocardite de Löffler – a propósito de um caso clínico

Loeffler's endocarditis is an acute form of primary restrictive cardiomyopathy. We report the case of a young woman with pleuritic chest pain associated with fever and hypereosinophilia. She was hospitalized with suspected acute myopericarditis and was treated with aspirin, leading to clinical improvement. Ten days after discharge, she was rehospitalized due to recurrence of chest pain. The echocardiogram showed what appeared to be a mass filling the apex of the right ventricle (RV). She was referred for magnetic resonance imaging, which revealed marked myocardial thickening in the apex of the RV. The patient underwent an endomyocardial biopsy, resulting in a diagnosis of eosinophilic endocarditis. After treatment with prednisolone, all symptoms and the eosinophilia disappeared, and there was complete remission of the RV abnormalities. After three years of follow-up, the patient remains asymptomatic. This case shows that, even without an etiologic diagnosis of eosinophilia, the prognosis for Loeffler's endocarditis can be favorable if treatment is initiated early.     

Pro-caspase-3 is constitutively expressed in luteinized granulosa cells from women undergoing controlled ovarian stimulation for in vitro fertilization

Apoptosis regulation in luteinized granulosa cells (LGC) during assisted reproduction procedures is still controversial. Caspase-3 is a major apoptosis mediator encoded by CASP3 and formed through cleavage of its precursor pro-caspase-3. The aim of this study was to investigate the expression patterns of pro-caspase-3 (mRNA and protein) and cleaved caspase-3 in human LGC. Thirty-five women undergoing controlled ovarian stimulation for in vitro fertilization were prospectively enrolled in the study. LGC were isolated from follicular fluid during oocyte pickup and evaluated by immunocytochemistry for pro-caspase-3 and cleaved caspase-3, and by real-time PCR for CASP3 mRNA expression. We found a positive staining of pro-caspase-3 in 77 % of the LGC (95 % confidence interval [CI] 60%–84%), whereas cleaved caspase-3 was found in only 4% of the cells (95 % CI 3%–6%). The abundance of cells expressing pro-caspase-3 was independent from CASP3 mRNA levels (r = 0.24, p = 0.255) and did not correlate with the amount of cleaved caspase-3 (r = -0.24, p = 0.186). Multivariable logistic regression showed that pro-caspase-3 positivity was not influenced by clinical characteristics such as age, cause or length of infertility, antral follicle count or hormonal drugs used to induce ovulation. These findings suggest that pro-caspase-3 is constitutively expressed in LGC, allowing quick cleavage into active caspase-3 and apoptosis triggering whenever needed in the course of gonadotropin-induced follicular development.     

Regulation of murine arthritis by systemic,spinal, and intra-articular adrenoceptors

BackgroundThe regulation of the immune system by the sympathetic nervous system is allowing the design of novel treatments for inflammatory disorders such as arthritis. In this study, we have analyzed the effects of α- and β-adrenoceptor agonists injected subcutaneously, intrathecally, or intra-articularly in zymosan-induced arthritis.MethodsMurine arthritis was induced by intra-articular (knee joint) injection of zymosan. α1 (phenylephrine), α2 (clonidine), β1 (dobutamine), or β2 (salbutamol)-adrenoceptor agonists were injected subcutaneously (sc), intrathecally (it), or intra-articularly (ia) to activate peripheral, spinal, or intra-articular adrenoceptors and to study their effects on articular edema formation and neutrophil migration into the synovial cavity.ResultsTreatments with phenylephrine did not affect the edema formation, but it increased neutrophil migration when injected subcutaneously (155.3%) or intra-articularly (187.7%). Treatments with clonidine inhibited neutrophil migration (59.9% sc, 68.7% it, 42.8% ia) regardless of the route of administration, but it inhibited edema formation only when injected intrathecally (66.7%) or intra-articularly (36%) but not subcutaneously. Treatments with dobutamine inhibited both edema (42.0% sc, 69.5% it, 61.6% ia) and neutrophil migration (28.4% sc, 70.3% it, 82.4% ia) in a concentration dependent manner. Likewise, all the treatments with salbutamol also inhibited edema formation (89.9% sc, 62.4% it, 69.8% ia) and neutrophil migration (76.6% sc, 39.1% it, 71.7% ia).ConclusionWhereas the β-adrenoceptor agonists induced anti-inflammatory effects regardless of their route of administration, α1- and α2-adrenoceptor agonists induced either pro- and anti-inflammatory effects, respectively.     

Use of amplified Mycobacterium tuberculosis direct test in respiratory samples from HIV-infected patients in Brazil

OBJECTIVE:

To compare the accuracy of the amplified Mycobacterium tuberculosis direct (AMTD) test with reference methods for the laboratory diagnosis of tuberculosis in HIV-infected patients.

METHODS:

This was a study of diagnostic accuracy comparing AMTD test results with those obtained by culture on Löwenstein-Jensen (LJ) medium and by the BACTEC Mycobacteria Growth Indicator Tube 960 (BACTEC MGIT 960) system in respiratory samples analyzed at the Bioassay and Bacteriology Laboratory of the Oswaldo Cruz Foundation Evandro Chagas Clinical Research Institute in the city of Rio de Janeiro, Brazil.

RESULTS:

We analyzed respiratory samples collected from 118 patients, of whom 88 (74.4%) were male. The mean age was 36.6 ± 10.6 years. Using the AMTD test, the BACTEC MGIT 960 system, and LJ culture, we identified M. tuberculosis complex in 31.0%, 29.7%, and 27.1% of the samples, respectively. In comparison with LJ culture, the AMTD test had a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 89.4%, 75.7%, and 95.0%, respectively, for LJ culture, whereas, in comparison with the BACTEC MGIT 960 system, it showed values of 88.6%, 92.4%, 83.8%, and 94.8%, respectively.

CONCLUSIONS:

The AMTD test showed good sensitivity and specificity in the population studied, enabling the laboratory detection of M. tuberculosis complex in paucibacillary respiratory specimens.