Diagnostic value of interleukin-6 and C-reactive protein on early onset bacterial infection in preterm neonates with respiratory distress

Aims: To evaluate the C-reactive protein (CRP) and interleukin-6 (IL-6) as diagnostic tools for early onset infection in preterm infants with early respiratory distress (RD). Methods: CRP and IL-6 were quantified at identification of RD and 24 h after in 186 newborns. Effects of maternal hypertension, mode of delivery, Apgar score, birth weight, gestational age, mechanical ventilation, being small for gestational age (SGA), and the presence of infection were analyzed. Results: Forty-four infants were classified as infected, 42 as possibly infected, and 100 as uninfected. Serum levels of IL-6 (0 h), CRP (0 h), and CRP (24 h), but not IL-6 (24 h) were significantly higher in infected infants compared to the remaining groups. The best test for identification of infection was the combination of IL-6 (0 h) 36 pg/dL and/or CRP (24 h) 0.6 mg/dL, which yielded 93% sensitivity and 37% specificity. The presence of infection and vaginal delivery independently increased IL-6 (0 h), CRP (0 h) and CRP (24 h) levels. Being SGA also increased the CRP (24 h) levels. IL-6 (24 h) was independently increased by mechanical ventilation. Conclusions: The combination of IL-6 (0 h) and/or CRP (24 h) is helpful for excluding early onset infection in preterm infants with RD but the poor specificity limits its potential benefit as a diagnostic tool.

Low Expression of Human Histocompatibility Soluble Leukocyte Antigen-G (HLA-G5) in Invasive Cervical Cancer With and Without Metastasis, Associated With Papilloma Virus (HPV)

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class lb molecule that acts as a specific immunosuppressor. Some studies have demonstrated that human papillomavirus (HPV) seems to be involved in lower or absent HLA-G expression, particularly in cervical cancer. In this study, we performed a cross-sectional study, systematically comparing the qualitative expression of the HLA-G5 isoform in invasive cervical carcinoma (ICC), stratifying patients according to the presence [ICC with metastasis (ICC(W))) and absence [ICC without metastasis (ICC(WT))] of metastasis, correlating these findings with interference of HPV and demographic and clinical variables. Seventy-nine patients with a diagnosis of ICC were stratified into two groups: ICC(WT) (n=52 patients) and ICC(W) (n=27). Two biopsies were collected from each patient (one from the tumor lesion and one from a lymph node). Immunohistochemistry analyses were performed for the HLA-G5 isoform, for HPV detection, and virus typing. HLA-G5 isoform molecules were detected in 25 cases (31.6%), 17 (32.7%) without metastasis and 8 (29.6%) with metastasis. HPV was detected in the cervical lesions of 74 patients (93.7%), but low expression of the HLA-G5 isoform was observed in all HPV-related cases. These findings are important; however, additional studies are necessary to identify the influence of HPV with HLA-G5 isoform expression on invasive cervical malignancies. (J Histochem Cytochem 58:405-411, 2010)

BUBR1 expression in benign oral lesions and squamous cell carcinomas: Correlation with human papillomavirus

Oral squamous Cell carcinoma (OSCC) is the most common head and neck cancer. Only in Brazil, the estimate is for 14,160 new cases in 2009. HPV is associated with increasing risk of oral cancer, but its role in carcinogenesis is still controversial. BUBR1, all important protein in the mitotic spindle assembly checkpoint (SAC), has been associated with some virus-encoded proteins and cancer. The aim of the present study was to evaluate the expression of BUBR1 in non-malignant oral lesions and OSCC with and without metastasis associated with HPV infection. We performed immunohistochemistry for BUBR1 in 70 OSCC biopsies divided into three groups (in situ tumors, invasive tumors without metastasis and invasive tumors with metastasis) with their respective lymph nodes from samples with metastasis and in 16 non-malignant oral lesions. PCR was performed in order to detect HPV DNA. Significantly higher BUBR1 expression associated with shorter survival (p=0.0479) was observed in malignant lesions. There was also it significant correlation (r=1.000) with BUBR1 expression in lesions with metastasis and their lymph nodes. Ninety percent of OSCC and 100% of benign lesions were HPV positive. HPV16 and HVP18 were present in 13 and 24% of HPV-positive OSCC samples, respectively. HPV was more prevalent (76%) in samples with a high BUBR1 expression and the absence of viral DNA had no influence oil BUBR1 expression. These findings suggest that HPV could be associated with overexpression of BUBR1 in OSCC. but not in benign oral lesions.

Anti-inflammatory effects of red pepper (Capsicum baccatum) on carrageenan- and antigen-induced inflammation

Inflammation is a pivotal component of a variety of diseases, such as atherosclerosis and tumour progression. Various naturally occurring phytochemicals exhibit anti-inflammatory activity and are considered to be potential drug candidates against inflammation-related pathological processes. Capsicum baccatum L. var. pendulum (Willd.) Eshbaugh (Solanaceae) is the most consumed species in Brazil, and its compounds, such as capsaicinoids, have been found to inhibit the inflammatory process. However, the anti-inflammatory effects of C. baccatum have not been characterized. Thus, this study was designed to evaluate the effects of C. baccatum juice in animal models of acute inflammation induced by carrageenan and immune inflammation induced by methylated bovine serum albumin. Pretreatment (30 min) of rats with pepper juice (0.25-2.0 g kg(-1)) significantly decreased leucocyte and neutrophil migration, exudate volume and protein and LDH concentration in pleural exudates of a pleurisy model. This juice also inhibited neutrophil migration and reduced the vascular permeability on carrageenan-induced peritonitis in mice. C. baccatum juice also reduced neutrophil recruitment and exudate levels of pro-inflammatory cytokines TNF-alpha, and IL-1 beta in mouse inflammatory immune peritonitis. Furthermore, we demonstrated that the main constituent of C. baccatum juice, as extracted with chloroform, is capsaicin. In agreement with this, capsaicin was able to inhibit the neutrophil migration towards the inflammatory focus. To our knowledge, this is the first demonstration of the anti-inflammatory effect of C. baccatum juice and our data suggest that this effect may be induced by capsaicin. Moreover, the anti-inflammatory effect induced by red pepper may be by inhibition of pro-inflammatory cytokine production at the inflammatory site.

Nitric Oxide-Induced Vasorelaxation in Response to PnTx2-6 Toxin from Phoneutria nigriventer Spider in Rat Cavernosal Tissue

Introduction. Priapism is one of several symptoms observed in accidental bites by the spider Phoneutria nigriventer. The venom of this spider is comprised of many toxins, and the majority has been shown to affect excitable ion channels, mainly sodium (Na+) channels. It has been demonstrated that PnTx2-6, a peptide extracted from the venom of P. nigriventer, causes erection in anesthetized rats and mice. Aim. We investigated the mechanism by which PnTx2-6 evokes relaxation in rat corpus cavernosum. Main Outcome Measures. PnTx2-6 toxin potentiates nitric oxide (NO)-dependent cavernosal relaxation. Methods. Rat cavernosal strips were incubated with bretylium (3 x 10-5 M) and contracted with phenylephrine (PE; 10-5 M). Relaxation responses were evoked by electrical field stimulation (EFS) or sodium nitroprusside (SNP) before and after 4 minutes of incubation with PnTx2-6 (10-8 M). The effect of PnTx2-6 on relaxation induced by EFS was also tested in the presence of atropine (10-6 M), a muscarinic receptor antagonist, N-type Ca2+ channel blockers (omega-conotoxin GVIA, 10-6 M) and sildenafil (3 x 10-8 M). Technetium99m radiolabeled PnTx2-6 subcutaneous injection was administrated in the penis. Results. Whereas relaxation induced by SNP was not affected by PnTx2-6, EFS-induced relaxation was significantly potentiated by this toxin as well as PnTx2-6 plus SNP. This potentiating effect was further increased by sildenafil, not altered by atropine, however was completely blocked by the N-type Ca2+ channels. High concentrated levels of radiolabeled PnTx2-6 was specifically found in the cavernosum tissue, suggesting PnTx2-6 is an important toxin responsible for P. nigriventer spider accident-induced priapism. Conclusion. We show that PnTx2-6 slows Na+ channels inactivation in nitrergic neurons, allowing Ca2+ influx to facilitate NO/cGMP signalling, which promotes increased NO production. In addition, this relaxation effect is independent of phosphodiesterase enzyme type 5 inhibition. Our data displays PnTx2-6 as possible pharmacological tool to study alternative treatments for erectile dysfunction. Nunes KP, Cordeiro MN, Richardson M, Borges MN, Diniz SOF, Cardoso VN, Tostes R, De Lima ME, Webb RC, and Leite R. Nitric oxide-induced vasorelaxation in response to PnTx2-6 toxin from Phoneutria nigriventer spider in rat cavernosal tissue. J Sex Med 2010;7:3879-3888.

Methods for exploring the morpho-functional relations of the aortic depressor nerve in experimental diabetes

The present study investigated morpho-functional relations of the aortic depressor nerve (ADN) 5, 15 and 120 days after the onset of streptozotocin-induced diabetes in rats. Time control animals received vehicle. Under pentobarbital anesthesia, ADN activity was recorded simultaneously with arterial pressure. After the recordings, nerves were prepared for light microscopy study and morphometry. ADN function was accessed by means of pressure-nerve activity curve (fitted by sigmoidal regression) and cross-spectral analysis between mean arterial pressure (MAP) and ADN activity. The relation between morphological (myelinated fibers number and density, total myelin area, total fiber area and percentage of occupancy) and functional (gain, signal/noise relation, frequency) parameters were accessed by linear regression analysis and correlation coefficient calculations. Functional parameters obtained by means of the sigmoidal regression curve as well as by cross-spectral analysis were similar in diabetic and control rats. Morphometric parameters of the ADN were similar between groups 5 days after the onset of diabetes. Average myelin area and myelinated fiber area were significantly smaller on diabetic rats 15 and 120 days after the onset of diabetes, being the myelinated fiber and respective axons area and diameter also smaller on 120 days group. Nevertheless, G ratio (ratio between axon and fiber diameter) was nearly 0.6 and not different between groups or experimental times. No significant relationship between morphological and functional parameters was detected in all experimental groups. The present study suggests that ADN diabetic neuropathy was time-dependent, with damage to myelinated fibers to be the primary event, not evidenced by physiological methods. (C) 2010 Elsevier B.V. All rights reserved.

Plasma hormonal profiles and dendritic spine density and morphology in the hippocampal CA1 stratum radiatum, evidenced by light microscopy, of virgin and postpartum female rats

Successful reproduction requires that changes in plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oxytocin (OT), estrogen (E-2) and progesterone (P-4) occur together with the display of maternal behaviors. Ovarian steroids and environmental stimuli can affect the dendritic spines in the rat hippocampus. Here, studying Wistar rats, it is described: (a) the sequential and concomitant changes in the hormonal profile of females at postpartum days (PP) 4, 8, 12, 16, 20 and 24, comparing to estrous cycle referential values; (b) the dendritic spine density in the stratum radiatum of CA1 (CA1-SR) Golgi-impregnated neurons in virgin females across the estrous cycle and in multiparous age-matched ones; and (c) the proportion of different types of spines in the CAI-SR of virgin and postpartum females, both in diestrus. Plasma levels of gonadotrophins and ovarian hormones remained low along PP while LH increased and PRL decreased near the end of the lactating period. The lowest dendritic spine density was found in virgin females in estrus when compared to diestrus and proestrus phases or to postpartum females in diestrus (p < 0.03). Other comparisons among groups were not statistically significant (p > 0.4). There were no differences in the proportions of the different spine types in nulliparous and postpartum females (p > 0.2). Results suggest that medium layer CA1-SR spines undergo rapid modifications in Wistar females across the estrous cycle (not quite comparable to Sprague-Dawley data or to hormonal substitutive therapy following ovariectomy), but persistent effects of motherhood on dendritic spine density and morphology were not found in this area. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Mucopolysaccharidoses in Brazil: What happens from birth to biochemical diagnosis?

Mucopolysaccharidoses (MPS) form a group of inherited metabolic disorders characterized by intralysosomal storage of glycosaminoglycans. This study aimed to investigate the path followed by Brazilian patients from birth to diagnosis. An interview was conducted with patient`s parents or guardians with subsequent review of patient`s medical records. One hundred thirteen patients with MPS were included (MPS I: 18, MPS II: 43, MPS III: 2, MPS IIIB: 3, MPS IIIC: 1, MPS IVA: 15, MPS IVB: 1, MPS VI: 29, MPS VII: 1) from 97 families. Median age at the onset of sings/symptoms was 18 months (MPS I: 18, MPS II: 24, MPS IVA: 8, MPS IV: 8). Skeletal abnormalities (for MPS IVA and MPS VI), joint contracures (for MPS II), and typically first signs/symptoms. Several health professionals were involved in patient`s care as of the onset of symptoms until biochemical diagnosis was established. Median age at diagnosis was 76 months (MPS I: 75, MPS II: 95, MPS IVA: 75, MPS VI: 52). Considering the group as a whole, there was a 4.8-year delay between the onset of signs/symptoms and establishment of the diagnosis. Considering that specific therapies are available for some of these disorders and that early treatment is likely to change more favorably the natural history of the disease, efforts should be made to minimize this delay. We believe that this situation can be improved by measures that both increase awareness of health professionals about MPS and improve access to diagnostic tests. (C) 2008 Wiley-Liss, Inc.

Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus-immune maternal population

OBJECTIVE: To determine contribution of reinfection with new strains of cytomegalovirus in cytomegalovirus seromimmune women to incidence of congenital cytomegalovirus infection. STUDY DESIGN: In 7848 women studied prospectively for congenital cytomegalovirus infection from a population with near universal cytomegalovirus seroimmunity, sera from 40 mothers of congenitally infected infants and 109 mothers of uninfected newborns were analyzed for strain-specific anticytomegalovirus antibodies. RESULTS: All women were cytomegalovirus seroimmune at first prenatal visit. Reactivity for 2 cytomegalovirus strains was found in 14 of 40 study mothers and in 17 of 109 control mothers at first prenatal visit (P=.009). Seven of 40 (17.5%) study women and 5 of 109 (4.6%) controls (P=.002) acquired antibodies reactive with new cytomegalovirus strains during pregnancy. Evidence of infection with more than 1 strain of cytomegalovirus before or during current pregnancy occurred in 21 of 40 study mothers and 22 of 109 controls (P<.0001). CONCLUSION: Maternal reinfection by new strains of cytomegalovirus is a major source of congenital infection in this population.

Low-dose transdermal hormone therapy does not interfere with the blood pressure of hypertensive menopausal women: a pilot study

Objectives To determine the effects of low-dose transdermal hormone therapy (HT) on systolic (SBP) and diastolic (DBP) blood pressure (BP) evaluated by 24-h ambulatory blood pressure monitoring (ABPM) in hypertensive postmenopausal women. Methods The study was conducted on 24 hypertensive postmenopausal women aged, on average, 54 years and under treatment with enalapril maleate (10-20 mg/day) combined or not with hydrochlorothiazide (25 mg/day). Thirteen women used a transdermal adhesive containing estradiol and norethisterone (25 and 125 mu g active substance/day, respectively) and 11 did not receive HT. ABPM, lipid profile, and climacteric symptoms were evaluated before and 3 and 6 months after treatment. Results After 3 and 6 months of follow-up, there was a statistically significant reduction of the Blatt-Kupperman menopausal index in the treated group (19.6 +/- 8.3 vs. 9.6 +/- 5.9 vs. 9.7 +/- 7.0; P=0.01). No significant difference in any of the ABPM variables (areas under the systolic and diastolic curves, mean SBP and DBP, SBP and DBP loads and wakefulness-sleep variation) or in the lipid profile was observed between or within groups at the three time points studied. Conclusion Low-dose transdermal HT administered for 6 months was effective in improving climacteric symptoms and did not change BP values or circadian pattern in postmenopausal women with mild-to-moderate arterial hypertension taking antihypertensive medications.

Comparison of pelvic floor muscle strength between women undergoing vaginal delivery, cesarean section, and nulliparae using a perineometer and digital palpation

Objectives. To compare pelvic floor muscle (PFM) strength between women undergoing vaginal delivery, cesarean section, and nulliparae, investigating the factors associated with PFM strength, and observing the correlation between vaginal digital palpation and use of a perineometer. Methods. A cross-sectional study was conducted, including 31 women following vaginal delivery, 30 women following cesarean section, and 30 nulliparous women. PFM strength was measured by vaginal digital palpation and use of a perineometer. Multiple linear regression analysis with adjustment for covariables was used to compare the mean PFM strength and identify its associated factors. Results. The mean PFM strength of women undergoing vaginal delivery and cesarean section was 25.6 +/- 14.5 cmH(2)O and 39.6 +/- 22.0 cmH(2)O (p < 0.01, adjusted for covariables), respectively. A correlation was observed between measurements of PFM strength obtained by vaginal digital palpation and use of a perineometer (tau = 0.82; p < 0.01). The non-white race/ethnicity was negatively associated with PFM strength (coefficient: -10.2424; p = 0.02). Conclusions. A lower PFM strength was observed in women with a history of vaginal delivery compared to those undergoing cesarean section. Non-white race/ethnicity negatively affected PFM strength. Our data suggest that vaginal digital palpation may be used in clinical practice because of its expressive correlation with use of a perineometer.

Giardia duodenalis: Pathological alterations in gerbils, Meriones unguiculatus, infected with different dosages of trophozoites

To examine the infection kinetics and development of alterations in the small intestine of gerbils (Meriones unguiculatus), 72 gerbils were divided into six groups (A to F), with A serving as control and the others inoculated with increasing doses of trophozoites from Giardia duodenalis human isolate. The infection kinetics and the development of histopathological alterations were monitored by optical scanning electron microscopy (SEM). A 12-day prepatent period was observed, with intermittent elimination up to day 35 after inoculation. Statistically significant differences were found between the mean number of trophozoites recovered, per group, on the days of sacrifice, and a positive correlation between the moculum dosage and the number of trophozoites recovered. Morphometrically, the villus:crypt ratio showed a drop in all the groups when compared with the control group. SEM revealed an increase in mucus production in the inoculated animals and the presence of trophozoite clusters at the top and base of the villi. The dosage of trophozoite inoculum does not interfere in the ability for infection to occur or in the development of histopathological alterations generated by intestinal colonization. (c) 2007 Elsevier Inc. All rights reserved.

Long-Term Outcome and Prognostic Factors of Juvenile Dermatomyositis: A Multinational, Multicenter Study of 490 Patients

Objective. To investigate the long-term outcome and prognostic factors of juvenile dermatomyositis (DM) through a multinational, multicenter study. Methods. Patients consisted of inception cohorts seen between 1980 and 2004 in 27 centers in Europe and Latin America. Predictor variables were sex, continent, ethnicity, onset year, onset age, onset type, onset manifestations, course type, disease duration, and active disease duration. Outcomes were muscle strength/endurance, continued disease activity, cumulative damage, muscle damage, cutaneous damage, calcinosis, lipodystrophy, physical function, and health-related quality of life (HRQOL). Results. A total of 490 patients with a mean disease duration of 7.7 years were included. At the cross-sectional visit, 41.2-52.8% of patients, depending on the instrument used, had reduced muscle strength/endurance, but less than 10% had severe impairment. Persistently active disease was recorded in 41.2-60.5% of the patients, depending on the activity measure used. Sixty-nine percent of the patients had cumulative damage. The frequency of calcinosis and lipodystrophy was 23.6% and 9.7%, respectively. A total of 40.7% of the patients had decreased functional ability, but only 6.5% had major impairment. Only a small fraction had decreased HRQOL. A chronic course, either polycyclic or continuous, consistently predicted a poorer outcome. Mortality rate was 3.1%. Conclusion. This study confirms the marked improvement in functional outcome of juvenile DM when compared with earlier literature. However, many patients had continued disease activity and cumulative damage at followup. A chronic course was the strongest predictor of poor prognosis. These findings highlight the need for treatment strategies that enable a better control of disease activity over time and the reduction of nonreversible damage.

Pneumococcal Nasopharyngeal Carriage Among Infants Born to Human Immunodeficiency Virus-infected Mothers Immunized With Pneumococcal Polysaccharide Vaccine During Gestation

Background: We have previously shown that 23-valent pneumococcal polysaccharide vaccine (PPV) is immunogenic in human immunodeficiency virus (HIV)-infected mothers and provides vaccine-induced antibodies to the infant. We compared the nasopharyngeal pneumococcal colonization (NPC) rates in <6-month-old infants born to HIV-infected mothers, according to immunization with PPV during pregnancy. Methods: NPC was evaluated in 45 term infants born to vaccinated women (PPV+) and in 60 infants in a control group (PPV-), at 2 months (+/- 30 days), 4 months (+/- 30 days), and 6 months (+/- 30 days) of age. Results: A total of 82 infants completed the study (at least 2 of 3 evaluations), 35 (77%) in the PPV+ and 47 (78.3%) in the PPV- groups, respectively. Infant gender, HIV infection status, number of adults, children, and smokers in the household, day-care attendance, occurrence of respiratory signs, and cotrimoxazole use were similar in both groups. NPC rates increased equally with age in both groups (2 months = 26.7% vs. 25.6%; 4 months = 34.5% vs. 38.6%; 6 months = 38.7% vs. 56.3%, in PPV+ and PPV-, respectively). After controlling for potential confounders, we found no association between maternal vaccination and infant pneumococcal carriage (adjusted odds ratio = 0.70; 95% confidence interval: 0.23, 2.21) Conclusions: Vaccination of HIV-infected mothers with PPV did not protect infants younger than 6 months of age from nasopharyngeal pneumococcal carriage.

Validation of the Brazilian version of the quality of life scale for patients with Alzheimer`s disease and their caregivers (QOL-AD)

Quality of life (QOL) has been extensively studied in clinical trials and in research on chronic degenerative diseases and dementia. The aim of this study was to assess the reliability and construct validity of the Brazilian version of the QOL scale in Alzheimer`s disease (AD; QOL-AD). The QOL-AD was administered to 60 patients with mild or moderate AD and to their caregivers. The construct validation was accomplished through correlations amongst total scores of patients` and caregivers` reports on patients` quality of life (PQOL and C-PQOL, respectively), and data related to cognitive impairment, depressive symptoms, functional performance, behavioral disturbances and a generic instrument of quality of life (WHOQOL-brief), as well as correlation of total score of caregivers` reports on their own quality of life (CQOL) with the measurements cited above, QOL-AD patient reports, and depressive symptoms. The reliability was high for PQOL, C-PQOL, and CQOL versions (Cronbach`s alpha = 0.80, 0.83, and 0.86, respectively). We observed significant correlations in the construct validity of all three versions regarding the variables associated with the disease and also with WHOQOL-brief. The scale took, on average, six min for each version. The results indicate reliability and construct validity of the Brazilian version of the QOL-AD in the studied sample.