Lymphatic vessel density and epithelial D2-40 immunoreactivity in pre-invasive and invasive lesions of the uterine cervix

OBJECTIVE: We sought to determine the significance of lymphatic vessel density (LVD) in pre-malignant lesions and carcinomas of the uterine cervix and to evaluate the prognostic value of lymphatic invasion and D2-40 positivity in tumor cells in the three histological types of invasive lesions. The correlation of LVD, lymphatic invasion and D2-40 positivity in tumor cells with EGFR and COX-2 expressions was also evaluated. METHODS: We studied 50 cervicitis, 50 low-grade squamous intraepithelial lesions (LSIL) (CIN1), 51 high-grade squamous intraepithelial lesions (HSIL) (CIN2/CIN3), 49 invasive squamous cells carcinomas (SCC), 43 adenocarcinomas (AC) and 30 adenosquamous cells carcinomas (ASC). The immunoreaction assay was performed using the monoclonal antibody D2-40. RESULTS: Significant differences in LVD were found among all categories of pre-invasive and invasive lesions (p=0.001 and p<0.001, respectively). LVD in invasive lesions was significantly greater than in pre-invasive lesions (p<0.001) and no significant association was found between LVD in invasive lesions and both lymph node invasion and/or metastasis. D2-40 positivity in tumor cells was associated with a better prognosis in ASC cases. EGFR and COX-2 expressions in invasive lesions were not associated with LVD; however, they correlated with both lymphatic invasion and D2-40 positivity in tumor cells. CONCLUSIONS: Lymphatic neovascularization begins early in intraepithelial lesions and continues to increase towards malignancy. Both lymphatic invasion and decrease in D2-40 expression in tumor cells appear to have a prognostic value.     

Bloqueadores do Receptor de Angiotensina Avaliados por Medida de Consultório e Residencial da Pressão Arterial. Estudo TeleMRPA

BackgroundAdequate treatment of arterial hypertension and achieving arterial hypertension goals in are important in reducing cardiovascular outcomes.ObjectivesTo describe angiotensin receptor blockers in monotherapy or double combination therapy and the rate of arterial hypertension control.MethodsThis cross-sectional study evaluated patients who were using angiotensin receptor blockers between 2017 and 2020. Those using three or more antihypertensive drugs were excluded. The analyzed variables included sex, age, body mass index, valid home blood pressure monitoring (HBPM) measurements, casual and HBPM systolic and diastolic blood pressure measurements, blood pressure variability, and antihypertensive and angiotensin receptor blocker class. Paired t, chi-square, and Fisher’s exact tests were used, as well as overlapping 95% confidence intervals and a significance level of 5% (p < 0.05).ResultsOf 17,013 patients, 12,813 met the inclusion criteria, 62.1% of whom were female. The mean number of valid measurements was 23.3 (SD, 2.0). The mean HBPM and casual measurements for systolic blood pressure were 126.8 (SD, 15.8) mmHg and 133.5 (SD, 20.1) mmHg (p <0.001), respectively, while those for diastolic blood pressure were 79.1 (SD, 9.7 mmHg) and 83.6 (SD, 11.9) mmHg (p <0.001), respectively. Losartan was the most common angiotensin receptor blocker and resulted in the highest blood pressure values. Combinations of angiotensin receptor blockers with diuretics or calcium channel antagonists resulted in lower blood pressure values.ConclusionsMore than half of the patients used losartan, although it was the least efficient drug for reducing and controlling blood pressure.     

Apoptosis of peripheral CD4(+) T-lymphocytes in end-stage renal disease patients under hemodialysis and rhEPO therapies

End-stage renal disease (ESRD) under hemodialyses (HD) is related with a higher propensity to infections, essentially due to T-cell lymphopenia. We postulated that HD procedure affects CD4(+) T cells, especially by inducing apoptotic death and that recombinant human erythropoietin (rhEPO) therapy may also play an important role in the modulation of the immune system in these patients. T-cell phenotype and apoptosis of HD patients and healthy controls were evaluated by flow cytometry using anticoagulated whole-blood samples. In 12 HD patients, these parameters were also analyzed before and immediately after HD procedure. HD patients showed a decrease in total circulating CD3(+) lymphocytes, especially in CD4(+) T cells (0.747 ± 0.410 vs. 0.941 ± 0.216 × 10(9)/L, p < 0.05), which could be a consequence of the higher proportion of CD3(+) and CD4(+) lymphocytes in the latest stage of apoptosis (or death) and of the higher proportion of apoptotic CD4(+) T cells observed in the patients immediately after HD procedure (2.91 ± 0.780 vs. 3.90 ± 1.96, p < 0.05). A positive and statistically significant correlation between CD3(+) and CD4(+) lymphocytes in latest stage of apoptosis (or death) with HD time was found (CD3(+): r = 0.592, p < 0.01; CD4(+): r = 0.501, p < 0.01). We also found a negative and significant correlation between weekly rhEPO doses and the number of CD4(+) T cells (r = -0.358, p < 0.05). In conclusion, HD procedure still contributes to the development of T-cell lymphopenia, at least in part, by apoptosis induction. It was also shown that rhEPO therapy is associated with the CD4(+) T-cell decline, possibly by immune modulation, eliminating atypical cells and helping to restore the CD4(+) T-cell subset.     

The Effect of Neuropeptide Y on Hypothalamic Serotonin Overflow

Intracerebroventricular injections of Neuropeptide Y stimulate orexigenic behaviors (food intake) in satiated animals. Several investigators have shown that the ventromedial, paraventricular, and other specific hypothalamic sites mediate the action of Neuropeptide Y to stimulate feeding. The present study used in vivo microdialysis to describe the time course of the changes in ventromedial hypothalamic serotonin and its metabolite, 5-hydroxy-3-indoleacetic acid subsequent to Neuropeptide Y administration in adult male Sprague-Dawley rats. Dialysates were collected before and after Neuropeptide Y injection using a 1 mm microdialysis probe placed in the ventromedial nucleus of the hypothalamus and were analyzed with High Performance Liquid Chromatography equipped with an ESA electrochemical detector. Two and half-hours after Neuropeptide Y injection, the perfusion fluid was changed so as to contain 10 μM of fluoxetine, a serotonin uptake inhibitor. Neuropeptide Y decreased extracellular serotonin concentration on average 30 to 50 percent from baseline. 5-hydroxy-3-indoleacetic acid overflow remained constant. Fluoxetine did not change the serotonin suppression. These observations suggest that Neuropeptide Y might be acting at the presynaptic terminal to prevent vesicular release of serotonin.     

The Urban Built Environment and Associations with Women’s Psychosocial Health

The determinants that underlie a healthy or unhealthy pregnancy are complex and not well understood. We assess the relationship between the built environment and maternal psychosocial status using directly observed residential neighborhood characteristics (housing damage, property disorder, tenure status, vacancy, security measures, violent crime, and nuisances) and a wide range of psychosocial attributes (interpersonal support evaluation list, self-efficacy, John Henryism active coping, negative partner support, Perceived Stress Scale, perceived racism, Center for Epidemiologic Studies—Depression) on a pregnant cohort of women living in the urban core of Durham, NC, USA. We found some associations between built environment characteristic and psychosocial health varied by exposure categorization approach, while others (residence in environments with more rental property is associated with higher reported active coping and negative partner support) were consistent across exposure categorizations. This study outlines specific neighborhood characteristics that are modifiable risk markers and therefore important targets for increased research and public health intervention.