Breast cancer micrometastases: Different interactions of carcinoma cells with normal and cancer patients' bone marrow stromata

The apparently dormant breast cancer micrometastases in haemopoietic marrow are correlated with distant metastatic carcinoma dissemination. We studied in vitro interactions of carcinoma cells with adjacent stromata, using connective tissue cell cultures from breast and bone marrow samples of normal donors, comparing them to the pericancerous breast tissue and bone marrows of 12 selected patients with invasive breast carcinomas. Cancer cells were detected by immunocytochemistry and RT-PCR in all the bone marrows and in most blood samples of the studied patients. We monitored the growth and interaction of carcinoma MCF-7 cells with the stromata. The normal breast stroma sustained typical massive cancer growth. The pericancerous breast stroma induced the invasive mesenchymal pattern of growth. Normal bone marrow stroma induced the same conversion and was highly adhesive, retaining the cells in the stroma, but carcinoma patients' bone marrow stromata underwent low adhesive interactions with cancer cells, releasing them potentially into the circulation. The semi-quantitative RT-PCR indicated an enhanced expression of the hepatocyte growth factor and its receptor c-met in breast and bone marrow stromata of cancer patients. The input of cancer cells into the normal bone marrow may induce modifications of the local microenvironment, favourable for growth and release of carcinoma cells into the systemic circulation, which correlate with the poor prognosis of patients with bone marrow micrometastases. This revised version was published online in July 2006 with corrections to the Cover Date.     

Analysis of human papillomavirus prevalence and TP53 polymorphism in head and neck squamous cell carcinomas

Head and neck squamous cell carcinoma is a disease associated with tobacco and alcohol abuse. There is evidence that the oncogenic human papillomavirus (HPV) may also be a risk for upper aerodigestive tract cancers. High-risk HPVs encode two early proteins, E6 and E7, that can bind to p53 and pRb, respectively, and induce its degradation or inactivation. The TP53 gene has a single polymorphism at codon 72 of exon 4 that encodes either arginine (Arg) or proline (Pro). The purpose of this study was to evaluate the role of HPV infection and TP53 polymorphism in head and neck cancer. We analyzed 50 tumors, as well swabs of oral mucosa from 142 control individuals, with a polymerase chain reaction technique. The prevalence of HPV in controls was 10.6% and in cancer specimens 16%. The frequency distribution of genotypes in controls was 50% Arg/Arg, 43% Arg/Pro and 7% Pro/Pro; in tumors, it was 52% Arg/Arg, 32% Arg/Pro, and 16% Pro/Pro. Contrary to the results of some studies on cervical cancer, no association between any TP53 genotype or allele and the development of head and neck cancer was observed, regardless of HPV status, except for the Pro/Pro genotype, which is associated with the absence of HPV. The arginine allele appears to protect against head and neck cancers. Also, the data showed that HPV infection results in no increased risk of developing head and neck tumors.     

Photobiomodulation therapy on expression of HSP70 protein and tissue repair in experimental acute Achilles tendinitis

Lasers in Medical Science - The aim of the present study was to investigate the effects of photobiomodulation (PBM) therapy on the expression of heat shock protein 70 (HSP70) and tissue repair in...     

Mathematical location models applied in the spatial organization of health units]

Mathematical location models have been increasingly applied in the health services at the international level. In Brazil, although incipient, there exists an enormous potential for the use of such models in the area of public health. In this paper several location models that can be applied to public health are presented initially, and the location of non-emergency services, of emergency services and of services hierarchically related are analysed. A hierarchical model is then applied to the location of maternal and perinatal assistance in the municipality of Rio de Janeiro. In this part, after presenting some related data for the municipality, a four-level hierarchical model (location of out-patient units, maternity hospitals, neonatal hospitals and general hospitals) is proposed and the impact that the adoption of this methodology would have as compared with that of the present system is analysed.     

Falling diarrhoea mortality in Northeastern Brazil: did ORT play a role?

The impact of oral rehydration therapy (ORT) on the recent decline in diarrhoea mortality in the northeast of Brazil was studied. Proportionate infant mortality fell from 32% in 1980 to 17% in 1989 and infant deaths attributed to diarrhoea dropped from 41% to 25%, resulting in an overall reduction of 57%. Similar decreases were observed for children aged 1-4 years. Diarrhoea admissions also fell from 57% of infant hospitalizations in 1980 to 30% in 1990. None of the other major causes of death or admissions showed such decline. ORT was introduced in the early 1980s, being used in 35% of all episodes in 1991 and in 62% of those regarded as severe by the mother. Other changes included a worsening of socioeconomic conditions and increases in water supply, vaccine coverage, breastfeeding duration and nutritional status. A simulation model estimated that changes in factors other than ORT would lead to a 21% reduction in infant diarrhoea mortality, or about one-third of the actual decline. Finally, an ecological analysis showed that ORT use rates were inversely correlated to infant diarrhoea mortality (r=-0.61; p=0.04). Despite the shortcomings of the available data, these findings suggest an important impact of ORT on diarrhoea mortality.     

Female mortality in Brazil: the weaker sex or stronger sex?

Population ageing in Brazil has been more rapid and more intense among women. This phenomenon is well described in developed countries where mortality rates are higher for men than women. In this regard, the analysis of mortality patterns by cause contributes to elucidate the determinant factors of the present situation in Brazil and provides indications of some future trends in female mortality. This is especially important due to the fact that in Brazil the social role of women has experienced great changes. This study presents data on mortality from ten capital cities in 1985, showing age-standardized overall and cause-specific mortality rates for five of the main groups of causes by sex. Ratios and differences effect estimators were used. The results revealed that regional patterns are associated with the urban and industrial processes with greater differences by sex in more developed regions. External causes and cardiovascular diseases are the main factors responsible for higher mortality among men with special emphasis on violent deaths. It is inferred that the present trend will be maintained, though it is possible that mortality differences by sex could decrease in the near future. The authors discuss that longer survival among women in Brazil does not reveal better life conditions.     

Microcystin-LR promote intestinal secretion of water and electrolytes in rats.

We showed previously that exposure to microcystin-LR causes renal toxic effects in isolated perfused rat kidney, and that inflammatory mediators from supernatants of macrophages stimulated by microcystin-LR are involved in this process. The aim of this research was to examine water and electrolytes secretion in vivo, induced by microcystin-LR and supernatant of macrophages stimulated for this toxin (SUP.MphiS + MCLR), using perfused rat ileal segment and ligated intestinal loop models. We found microcystin-LR at 1 microg/ml (0.09 +/- 0.003* vs. control 0.07 +/- 0.001 g of secretion/2 cm of loop; P < 0.05*) and the SUP.MphiS + MCLR after 18 h postinoculation (0.10 +/- 0.003 vs. control 0.03 +/- 0.002 g/cm) caused intestinal secretion. In addition, microcystin-LR caused significant sodium secretion (-2.18 +/- 0.72* vs. control 2.18 +/- 0.50 microEq g(-1) min(-1)), potassium (-0.26 +/- 0.04* vs. control 0.32 +/- 0.03 microEq g(-1) min(-1)), chloride (MCLR = -3.29 +/- 1.93* vs. control 0.88 +/- 1.25 microEq g(-1) min(-1)) and water (-0.012 +/- 0.004* vs. control 0.002 +/- 0.002 ml g(-1) min(-1)). We also demonstrated SUP.MphiS + MCLR to induce intestinal secretion of electrolytes (sodium, potassium, chloride) and water. These findings suggested that microcystin-LR and lamina propria macrophages-derived mediators are able to induce intestinal secretion in vivo, probably via inhibition of protein phosphatase.     

The Impact of Psychosis on Sexual Functioning: A Systematic Review

BackgroundSexual dysfunction among psychotic patients is highly prevalent. However, most research has focused on antipsychotic side effects on sexual functioning.AimTo provide evidence by means of a systematic review of the literature about the impact of psychosis on sexual functioning among unmedicated patients.MethodsSystematic search of MEDLINE (PubMed), Scopus, and Google Scholar for studies that reported sexual functioning among psychotic patients, who were drug-naïve or drug-free for at least 3 weeks before the study. Studies were published in English language between January 1994 and October 2019. We used the approach recommended by PRISMA, and the selection process was carried out by 2 reviewers.OutcomesThe outcome measures were sexual function and sexual dysfunctions.ResultsA total of 734 articles were obtained, 658 were obtained after duplicates were removed, 612 were excluded after reading the title and abstract, and 46 were included for a complete review of the articles. 5 papers were finally included. A total of 770 cases were included in the systematic review. The prevalence of sexual dysfunction in psychosis varied from 16.8% to 70% and in ultra-high state was 50%. It is noteworthy that those ultra–high-risk (prodromal) patients who develop psychosis had higher rates of sexual impairment. Therefore, we found higher rates of sexual dysfunction among untreated patients, both psychotic and ultra-high risk patients, than healthy controls.Clinical ImplicationsThe assessment of sexual behavior should be a part of routine psychiatric examination not only in psychotic but also in ultra–high-risk patients.Strengths & LimitationsThis is the first systematic review about the impact of psychosis on sexual functioning among unmedicated patients. However, scarce and heterogeneous studies were identified.ConclusionsImpaired sexual functioning is common in the onset of psychosis (or during ultra–high-risk state) and prior to the beginning of treatment. This suggests that psychotic symptoms and sexual dysfunction may have common etiological pathways at the psychosocial and neurobiological levels.Vargas-Cáceres S, Cera N, Nobre P, et al. The Impact of Psychosis on Sexual Functioning: A Systematic Review. J Sex Med 2021;18:457–466.     

Antimicrobial activity of Buchenavia tetraphylla against Candida albicans strains isolated from vaginal secretions

Context: Buchenavia tetraphylla (Aubl.) RA Howard (Combretaceae: Combretoideae) is an ethnomedicinal plant with reported antifungal action.

Objective: This study evaluates the antimicrobial activity of B. tetraphylla leaf extracts against clinical isolates of Candida albicans. The morphological alterations, combinatory effects with fluconazole and the cytotoxicity of the active extract were analyzed.

Materials and methods: Extracts were obtained using different solvents (hexane: BTHE; chloroform: BTCE; ethyl acetate: BTEE; and methanol: BTME). Antimicrobial activity was determined by the broth microdilution method using nine strains of C. albicans isolated from vaginal secretions and one standard strain (UFPEDA 1007).

Results: All extracts showed anti-C. albicans activity, including against the azole-resistant strains. The MIC values ranged from 156 to 2500?μg/mL for the BTHE; 156 to 1250?μg/mL for the BTCE; 625 to 1250?μg/mL for the BTME and 625?μg/mL to 2500?μg/mL for the BTEE. BTME showed the best anti-C. albicans activity. This extract demonstrated additive/synergistic interactions with fluconazole. Scanning electron microscopy analysis suggested that the BTME interferes with the cell division and development of C. albicans. BTME showed IC₅₀ values of 981 and 3935?μg/mL, against J774 macrophages and human erythrocytes, respectively. This extract also enhanced the production of nitric oxide by J774 macrophages.

Discussion and conclusion: Buchenavia tetraphylla methanolic extract (BTME) is a great source of antimicrobial compounds that are able to enhance the action of fluconazole against different C. albicans strains; this action seems related to inhibition of cell division.