Characterization of human papillomavirus infection,P53 and Ki-67 expression in cervix cancer of Mozambican women

In this study, we aimed at evaluating the distribution of HPV types and the expression of P53 and Ki-67 in cervix carcinomas of Mozambican women. Fourty-seven invasive carcinomas, 10 CIN III, and 10 normal cervix were studied. P53 and Ki-67 expression was examined immunohistochemically. HPV infection and HPV types were detected by PCR (GP5+/bio-GP6+) and enzyme-immunoassay, respectively. Expression of P53 and Ki-67 and detection of HPV were as follows: normal cervix--0%, 10%, and 0%, respectively; CIN III--10%, 0%, and 100%, respectively; invasive carcinomas--50%, 55.5%, and 70%, respectively. HPV 16 was identified in 54% of invasive carcinomas, HPV 31, 33, 35, and 45 in 23%, "unidentified" HPV in 19%, and HPV 18 in 4% of invasive carcinomas. No significant associations were observed between P53 expression, Ki-67 expression, and HPV infection. In conclusion, we observed a high frequency of HPV infection in CIN III lesions and invasive carcinomas from Mozambican women, with HPV 16 representing the most frequent viral type. HPV status was not related to P53 and Ki-67 expression. Both P53 and Ki-67 are associated with invasive cervix carcinomas, mainly of the squamous keratinizing histotype.     

Acute exercise reverses TRB3 expression in the skeletal muscle and ameliorates whole body insulin sensitivity in diabetic mice

Aim: TRB3 became of major interest in diabetes research when it was shown to interact with and inhibit the activity of Akt. Conversely, physical exercise has been linked to improved glucose homeostasis. Thus, the current study was designed to investigate the effects of acute exercise on TRB3 expression and whole body insulin sensitivity in obese diabetic mice. Methods: Male leptin-deficient (ob/ob) mice swam for two 3-h-long bouts, separated by a 45-min rest period. After the second bout of exercise, food was withdrawn 6 h before antibody analysis. Eight hours after the exercise protocol, the mice were submitted to an insulin tolerance test (ITT). Gastrocnemius muscle samples were evaluated for insulin receptor (IR) and IRS-1 tyrosine phosphorylation, Akt serine phosphorylation, TRB3/Akt association and membrane GLUT4 expression. Results: Western blot analysis showed that TRB3 expression was reduced in the gastrocnemius of leptin-deficient (ob/ob) mice submitted to exercise when compared with respective ob/ob mice at rest. In parallel, there was an increase in the insulin-signalling pathway in skeletal muscle from leptin-deficient mice after exercise. Furthermore, the GLUT4 membrane expression was increased in the muscle after the exercise protocol. Finally, a single session of exercise improved the glucose disappearance (K_ITT) rate in ob/ob mice. Conclusion: Our results demonstrate that acute exercise reverses TRB3 expression and insulin signalling restoration in muscle. Thus, these results provide new insights into the mechanism by which physical activity ameliorates whole body insulin sensitivity in type 2 diabetes.     

Innovative moments and change pathways: A good outcome case of narrative therapy

Objectives. Our aim was to explore the development of innovative moments (i‐moments) in therapeutic conversation and to study how they match our heuristic model that accounts for the development of change, drawn from previous empirical research. Design. In this therapeutic process research, we analysed a good outcome case of narrative therapy with a woman victim of intimate violence. Methods. This case, composed of 12 sessions, was analysed with the Innovative Moments Coding System: Version 1. This coding system allowed the identification of five different types of innovations (i‐moments) that appeared during the therapeutic process: action, reflection, protest, re‐conceptualization, and performing change. For each session, an index of temporal salience was computed, as the percentage of the time in the session that client and therapist spent talking about each i‐moment. Our analysis procedures provided a quantitative and also a complementary qualitative approach. Results. Data showed that the types of i‐moments emerged differently throughout the process. Early sessions were characterized mainly by action and reflection (low temporal salience), middle sessions were found to have mainly protest i‐moments (low or middle temporal salience), and final sessions were characterized by the combination of high salient re‐conceptualization and performing change i‐moments. Conclusions. Findings suggested that narrative change seems to develop in a cyclical way, in which different types of i‐moments contribute to the development of a new self‐narrative in different phases.     

Routine transthoracic echocardiography in a general Intensive Care Unit: An 18 month survey in 704 patients

The authors analyzed 704 transthoracic echocardiographic (TTE) examinations, performed routinely to all admitted patients to a general 16-bed Intensive Care Unit (ICU) during an 18-month period. Data acquisition and prevalence of abnormalities of cardiac structures and function were assessed, as well as the new, previously unknown severe diagnoses.A TTE was performed within the first 24 h of admission on 704 consecutive patients, with a mean age of 61.5 ± 17.5 years, ICU stay of 10.6 ± 17.1 days, APACHE II 22.6 ± 8.9, and SAPS II 52.7 ± 20.4. In four patients, TTE could not be performed. Left ventricular (LV) dimensions were quantified in 689 (97.8%) patients, and LV function in 670 (95.2%) patients. Cardiac output (CO) was determined in 610 (86.7%), and mitral E/A in 399 (85.9% of patients in sinus rhythm). Echocardiographic abnormalities were detected in 234 (33%) patients, the most common being left atrial (LA) enlargement (n = 163), and LV dysfunction (n = 132). Patients with these alterations were older (66 ± 16.5 vs 58.1 ± 17.4, p < 0.001), presented a higher APACHE II score (24.4 ± 8.7 vs 21.1 ± 8.9, p < 0.001), and had a higher mortality rate (40.1% vs 25.4%, p < 0.001). Severe, previously unknown echocardiographic diagnoses were detected in 53 (7.5%) patients; the most frequent condition was severe LV dysfunction. Through a multivariate logistic regression analysis, it was determined that mortality was affected by tricuspid regurgitation (p = 0.016, CI 1.007–1.016) and ICU stay (p < 0.001, CI 1–1.019). We conclude that TTE can detect most cardiac structures in a general ICU. One-third of the patients studied presented cardiac structural or functional alterations and 7.5% severe previously unknown diagnoses.     

Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterized by inflammation of the respiratory tract in which macrophages are the predominant inflammatory cell and for which the efficacy of treatment with corticosteroids is controversial. We investigated the effect of dexamethasone on basal and interleukin (IL)-1beta or cigarette smoke media (CSM)-stimulated release of IL-8 and granulocyte macrophage-colony stimulating factor (GM-CSF) by bronchoalveolar lavage macrophages from cigarette smokers and patients with COPD (n = 15). Basal release of IL-8 was approximately fivefold greater in patients with COPD than smokers, whereas GM-CSF was similar for each group. IL-1beta and CSM increased IL-8 and GM-CSF release by macrophages from both smokers and patients with COPD. Dexamethasone did not inhibit basal or stimulated IL-8 release from macrophages from patients with COPD but inhibited release in smokers. In contrast, basal and IL-1beta-stimulated GM-CSF release, but not CSM-stimulated release, was inhibited by dexamethasone. We conclude that the lack of efficacy of corticosteroids in COPD might be due to the relative steroid insensitivity of macrophages in the respiratory tract.     

Orthomolecular oncology: a mechanistic view of intravenous ascorbate's chemotherapeutic activity

The effect of vitamin C in cancer has been a subject of great controversy; mainly because of the inconsistent results obtained by oral intakes of ascorbate when used as an anticancer agent. We believe the intravenous application of ascorbate will provide more consistent results in cancer patients since Vitamin C blood levels attained are substantially higher in a range proven cytotoxic to malignant cells. In this article we will present and discuss our proposed mechanism on the chemotherapeutic activity exhibited by ascorbate.     

Temporal and regional expression of NMDA receptor subunit NR3A in the mammalian brain

NR3A is a developmentally regulated N-methyl-D-aspartate receptor (NMDAR) subunit that was previously known as NMDAR-L or chi-1. Unlike other NMDAR subunits, NR3A inhibits the NMDAR-associated ion channel in a novel manner, and a role in synaptogenesis has been suggested for this subunit. Here, we report a comprehensive study to delineate the temporal and anatomic expression of NR3A protein in the mammalian brain by using a monoclonal anti-NR3A antibody. NR3A protein was found to peak at postnatal day (P) 8, and to decrease gradually from P12 to adulthood in the rat central nervous system. Moreover, NR3A protein was heavily expressed in all areas of the isocortex, portions of the amygdaloid nuclei, and selective cell layers and nuclei of the hippocampus, thalamus, hypothalamus, brainstem, and spinal cord. NR3A protein was also expressed in the cerebellar cortex, whereas only weak signal was detected in the previous in situ studies by using riboprobes. At an ultrastructural level, NR3A was associated specifically with asymmetrical synapses and localized to postsynaptic membranes. This information will facilitate future research on NMDARs by providing clues to possible inclusion of the NR3A subunit in NMDARs in many brain regions.     

Diagnostic use of 3 techniques for identification of microsporidian spores among AIDS patients in Portugal

The calcofluor stain (CF), the monoclonal antibody (MAb) 3B6 indirect immunofluorescence assay (IFA) and the modified trichrome blue stain (MT) were compared in terms of their reproducibility in a routine laboratory and in order to evaluate the percentage of cases of microsporidiosis in Portuguese HIV patients. A total of 166 faeces samples, 71 pulmonary specimens and 43 urine samples were studied using the 3 techniques. CF had a high sensitivity and a moderate specificity when applied to faeces samples. The sensitivity was lower with pulmonary specimens. The method is easy and quick to perform but readings take a long time to obtain. The MAb 3B6 IFA had a good to excellent sensitivity when applied to faeces and urine samples, but moderate sensitivity in pulmonary specimens. Readings were quick and easy to obtain, but the assay took longer to perform than the other 2 techniques. There was a greater correlation between the results obtained with the MT and MAb 3B6 IFA techniques than between those obtained with the MT and CF techniques. In conclusion, the MT performed better than the MAb 3B6 IFA and CF and continues to have an important place in a routine laboratory for the diagnosis of microsporidiosis. This work also confirms the existence of a relatively high proportion (30%) of cases of infection with Microsporidia, especially intestinal microsporidiosis, in HIV patients in Portugal.     

Reproductive factors, oral contraceptive use, and human papillomavirus infection: pooled analysis of the IARC HPV prevalence surveys.

High parity, early age at first full-term pregnancy (FTP), and long-term oral contraceptive (OC) use increase cervical cancer risk, but it is unclear whether these variables are also associated with increased risk of acquisition and persistence of human papillomavirus (HPV) infection, the main cause of cervical cancer. Information on reproductive and menstrual characteristics and OC use were collected from 14 areas worldwide, among population-based, age-stratified random samples of women aged 15 years or older. HPV testing was done using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate the odds ratios (OR) of being HPV-positive according to reproductive and menstrual factors and corresponding 95% confidence intervals (CI). When more than two groups were compared, floating CIs (FCI) were estimated. A total of 15,145 women (mean age, 40.9 years) were analyzed. Women with >or=5 FTPs (OR, 0.90; 95% FCI, 0.76-1.06) showed a similar risk of being HPV-positive compared with women with only one FTP (OR, 1.00; 95% FCI, 0.86-1.16). However, nulliparous women showed an OR of 1.40 (95% CI, 1.16-1.69) compared with parous women. Early age at first FTP was not significantly related to HPV positivity. HPV positivity was similar for women who reported >or=10 years of use of OCs (OR, 1.16; 95% FCI, 0.85-1.58) and never users of OCs (OR, 1.00; 95% FCI, 0.90-1.12). Our study suggests, therefore, that high parity, early age at first FTP, and long-term OC use are not associated with HPV prevalence, but rather these factors might be involved in the transition from HPV infection to neoplastic cervical lesions.