Circulating levels of sTNFR and discrepancy between cytotoxicity and immunoreactivity of TNF-α in patients with visceral leishmaniasis

Objectives To study the influence of soluble tumour necrosis factor (TNF) receptors (sTNFR) on bioactivity and immunoreactivity of TNF-α in patients with visceral leishmaniasis (Kala-azar) and to examine the association between circulating levels of sTNFR type I and type II with clinical manifestations of the disease.
Methods   Ten patients with Kala-azar were enrolled. Plasma samples for TNF-α and sTNFR were obtained on days 0, 7 and 21–28 of antimonial therapy. Bioactivity of TNF-α was measured by cytotoxicity to L-929 cells and immunoreactivity by enzyme-linked immunosorbent assay (ELISA). sTNFR-I and sTNFR-II were measured by ELISA.
Results   Measured by ELISA, TNF-α was detected at baseline in all patients (range from 22.3 to 163 pg/mL) and showed a linear decline over time on therapy ( r  = −0.49, P  = 0.007). In contrast, when measured by cytotoxicity assay, TNF-α was detected in only one patient at baseline (193 pg/mL) and in four patients at the end of therapy (38.7, 95, 133 and 232 pg/mL) and there was no linear association between TNF-α and duration of therapy ( r  = −0.18, P  = 0.45). sTNFR-I and sTNFR-II were detected in all patients before therapy. There was a strong positive correlation between plasma concentrations of sTNFR-I and sTNFR-II ( r  = 0.8, P  = 0.006). Levels of sTNFR-I and sTNFR-II declined exponentially with time on therapy.
Conclusions   We concluded that sTNFR-I and sTNFR-II are related to disease activity in patients with Kala-azar and that these circulating receptors may interfere with the biological activity of TNF-α in patients with Kala-azar.     

Short‐term antiretroviral therapy to prevent mother‐to‐child transmission is safe and results in a sustained increase in CD4 T‐cell counts in HIV‐1‐infected mothers*

Background

Short‐term antiretroviral therapy (START) to prevent mother‐to‐child transmission (MTCT) is currently recommended for all HIV‐1‐infected pregnant women. The objective of this study was to assess the effect on CD4 cell counts and viral load dynamics the withdrawal of START after birth could generate.

Methods

This was a 5‐year cohort study involving HIV‐1‐infected pregnant women who presented with CD4 counts >300 cells/μL and had received START to prevent MTCT.

Results

Seventy‐five pregnancies were assessed. In 24 cases, there was a history of antiretroviral therapy prior to prophylaxis. The median baseline CD4 count was 573 cells/μL. In 75% of cases, prophylaxis was started after 26.6 weeks of gestation. The median CD4 cell count increase over baseline during prophylaxis was 24.5%. In only five cases did HIV‐1 viral load remain detectable during prophylaxis. After START, CD4 cell counts did not drop significantly, and the HIV‐1 viral load plateau was near the baseline level. The estimated mean time for CD4 count to fall below 300 cells/μL was 3.5 years and was directly associated with high baseline CD4 cell count, as well as with CD4 increase after prophylaxis, whereas it was negatively correlated with previous use of antiretroviral (ARV) drugs and persistence of detectable HIV‐1 viral load during prophylaxis.

Conclusions

A potent, well‐tolerated prophylactic ARV regimen can improve CD4 cell counts during and after START. In women receiving such prophylaxis, there is a remarkable time interval for CD4 cell counts to drop to levels that indicate treatment.     

Tumor necrosis factor alpha (TNF-α) and sepsis: Evidence for a role in host defense

Summary Serum levels of TNF-alpha were evaluated in 29 patients with sepsis, using TNF-alpha sensitive L929 cells (sensitivity=15 pg/ml). Blood samples were collected serially at the first 24–36 h of symptoms. Seventeen patients had severe underlying disease and 12 patients had mild or no underlying disease. Shock was present in 25 patients. Overall mortality was 62.1%. TNF-alpha was detected in nine patients (range: 57.7–3,169 pg/ml). There was a tendency to detect TNF-alpha in patients with mild or no underlying disease (p=0.07). Detection of TNF-alpha was associated with survival (p=0.0003) even when adjusted for severity of underlying disease (p=0.005), shock (p=0.0005), coagulation abnormality (p=0.002) and immunosuppressive therapy (p=0.005), using a bivariate analysis. In this investigation, detection of circulating TNF-alpha was predictive of good outcome in septic patients, suggesting a role for this cytokine in host-defense against this kind of infection.

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Tumornekrosefaktor alpha (TNF alpha) und Sepsis: Bedeutung für die Wirtsabwehr

Zusammenfassung Bei 29 Patienten mit Sepsis wurden die Serumspiegel von TNF-alpha mittels Bioassay mit TNFalpha-sensitiven L929 Zellen (untere Nachweisgrenze 15 pg/ml) bestimmt. In den ersten 24–36 Stunden nach Beginn der Symptome wurden seriell Blutproben entnommen. Bei 17 Patienten bestand eine schwere Grundkrankheit und bei 12 eine leichtere oder keine Grundkrankheit. Bei 25 der 29 Patienten war ein Schock festzustellen. Die Gesamtmortalität lag bei 62,1%. Bei neun Patienten war TNF-alpha (Bereich 57,7–3 169 pg/ml) nachzuweisen. Tendenziell war TNF-alpha eher bei Patienten mit leichten oder ohne Grundkrankheit nachzuweisen (p=0,07). Der Nachweis von TNF-alpha war mit Überleben verbunden (p=0,0003) auch wenn eine gepaarte Analyse unter Berücksichtigung des Schweregrades der Grundkrankheit (p=0,005), Schock (p=0,0005), einer Gerinnungsstörung (p=0,002) oder immunsuppressiven Therapie (p=0,005) durchgeführt wurde. In dieser Studie erwies sich der Nachweis von TNF-alpha als prädiktiver Faktor für einen günstigen Verlauf bei Sepsispatienten, so daß angenommen werden muß, daß dieses Zytokin bei dieser Infektionsform eine Funktion in der Wirtsabwehr hat.

     

Mandibular movements in children with and without signs and symptoms of temporomandibular disorders

This research aimed to evaluate mandibular movements in children with and without signs and symptoms of temporomandibular dysfunction. The sample taken consisted of 99 children aged 3 to 5 years distributed in two groups: I - Absence of signs and/or symptoms of TMD (25 girls/40 boys); II - Presence of signs and symptoms of TMD (16 girls/18 boys). The symptoms were evaluated through an anamnesis questionnaire answered by the child's parents/caretakers. The clinical signs were evaluated through intra- and extraoral examination. Maximum mouth opening and left/right lateral movements were measured using a digital caliper. The maximum protrusive movement was measured using a millimeter ruler. The means and standard deviations for maximum mouth opening in Group I and Group II were 40.82mm±4.18 and 40.46mm±6.66, respectively. The values found for the left lateral movement were 6.96mm±1.66 for Group I and 6.74mm±1.55 for Group II, while for the right lateral movement they were 6.46mm±1.53 and 6.74mm±1.77. The maximum protrusion movements were 5.67mm±1.76 and 6.12mm±1.92, in Groups I and II, respectively. The mandibular movement ranges neither differed statistically between groups nor between genders. FAPESP Process 96/0714-6.     

Acrylamides and methacrylamides as alternative monomers for dental adhesives

Objective

Synthesize and characterize a methacrylamide monomer for adhesive system and evaluate the physicochemical properties of the adhesive resin.

Targeting the endothelin axis in prostate carcinoma

Prostate cancer is the most common malignancy in men in Western countries. Until the last decade, the main available therapeutic options were based on hormonal therapy. For castration-refractory prostate carcinoma, from 2004, the combination of chemotherapy with docetaxel and prednisone has shown to improve survival in this subset of patients. Many agents have been tested either alone or in combination with this standard therapy, trying to find synergistic effects between drugs, and to target specific pathways that influence tumor growth, invasiveness, angiogenesis, and the development of distant metastasis. Endothelin antagonists have been recently studied, as they can get involved in many of these oncogenic pathways, and results are encouraging; nevertheless, the right setting to use them, whether to use them in monotherapy or in combination with other agents, and if they really improve the survival of our patients, are questions that remain to be addressed. In this review, we summarize the role of endothelins in tumoral biology and specifically in prostate carcinoma natural history, and the results obtained in the clinical trials involving this new therapeutic group.