Immunohistochemical expression of Drosha is reduced in eutopic and ectopic endometrium of women with adenomyosis

The objective of this study was to evaluate the immunohistochemical expression of Dicer, Drosha, and Exportin-5 in the eutopic and ectopic endometrium of women with adenomyosis. Twenty-two paired ectopic and eutopic endometrium from women with adenomyosis and 10 eutopic endometrium samples from control women undergoing hysterectomy were included in the study. Paraffin-embedded tissue blocks were cut and stained for immunohistochemistry. The percentage of epithelial cells positively marked was identified digitally after an automated slide scanning process. Mann-Whitney test or Wilcoxon signed-rank test was performed for independent and paired groups, respectively. A lower expression of Drosha was observed in the eutopic endometrium of women with adenomyosis than in the eutopic endometrium of women without the disease (69.9±3.4% vs 85.2±2.9%, respectively) (P=0.016; 95%CI: 3.4 to 27.4%). We also detected lower Drosha expression in the ectopic endometrium of women with adenomyosis than in the eutopic endometrium of the same women (59.6±3.2% vs 69.9±3.4%, respectively) (P=0.004; 95%CI: 2.3 to 16.7%). Additionally, we observed a correlation between Drosha expression in the ectopic and paired eutopic endometrium (P=0.034, rho=0.454). No significant difference in Dicer or Exportin expression was observed. Predominant pattern of cytoplasmic staining for the anti-Drosha antibody and both a nuclear and cytoplasmic pattern for the anti-Exportin antibody were observed. Drosha expression was significantly lower in the endometrium of women with adenomyosis compared to the eutopic endometrium of asymptomatic women without the disease. Furthermore, its expression was lower in the ectopic endometrium but correlated to the paired eutopic endometrium.

Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats

The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca2+ mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca2+ mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats.

Reduction of blood nitric oxide levels is associated with clinical improvement of the chronic pelvic pain related to endometriosis

The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (μM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis (99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.

Atividade antinociceptiva do extrato etanólico das folhas de Morus nigra L. (Moraceae) / Antinociceptive activity of ethanolic extract of the leaves of Morus nigra L. (Moraceae)

O extrato etanólico bruto das folhas de M. nigra (Mn- EtOH) foi avaliado quanto à atividade antinociceptiva em modelos experimentais em camundongos. Foram usados os métodos de contorções abdominais induzidas pelo ácido acético, teste da formalina e placa quente. No teste de contorções abdominais induzidas pelo ácido acético, Mn-EtOH (100, 200 e 400 mg/kg, i.p.) reduziu o número de contorções em 38,82, 97,65 e 100%, respectivamente. O extrato também produziu uma significativa inibição de ambas as fases do teste da formalina, sendo que o efeito foi mais significativo na segunda fase (dor inflamatória). O extrato diminuiu em 42,19, 56,96 e 40,50%, respectivamente, o tempo de lambida da pata na primeira fase do teste de formalina, assim como 84,04, 77,20 e 61,07%, respectivamente, na segunda fase. Além disso, não apresentou efeito no teste da placa quente. Os dados obtidos sugerem que o extrato tem efeito antinociceptivo, provavelmente mediado através de mecanismos periféricos. Novos estudos estão sendo realizados para caracterizar o mecanismo responsável por esse efeito.(AU)

The crude ethanolic extract of the leaves of M. nigra (Mn-EtOH) was evaluated for antinociceptive activity in mice using models of nociception. The evaluation of antinociceptive activity was carried out by the acetic acid-induced writhing, formalin and hot plate tests. In the acetic acid-induced writhing test, the Mn-EtOH (100, 200 and 400 mg/kg, i.p.) reduced the number of writhing by 38.82, 97.65 and 100%, respectively. The extract also produced a significant inhibition of both phases of the formalin test, and the effect was more significant in the second phase (inflammatory pain). The extract decreased by 42.19, 56.96 and 40.50%, respectively, the paw licking time in the first phase of the formalin test, as well as 84.04, 77.20 and 61.07%, respectively, in the second phase of this test. Also, no effect on the hot plate test was observed. The data suggest that the extract has antinociceptive activity, probably mediated via peripheral mechanisms. Pharmacological studies are continuing in order to characterize the mechanism responsible for this effect.(AU)

Pain pressure threshold algometry of the abdominal wall in healthy women

The objective of this study was to determine the inter- and intra-examiner reliability of pain pressure threshold algometry at various points of the abdominal wall of healthy women. Twenty-one healthy women in menacme with a mean age of 28 ± 5.4 years (range: 19-39 years) were included. All volunteers had regular menstrual cycles (27-33 days) and were right-handed and, to the best of our knowledge, none were taking medications at the time of testing. Women with a diagnosis of depression, anxiety or other mood disturbances were excluded. Women with previous abdominal surgery, any pain condition or any evidence of inflammation, hypertension, smoking, alcoholism, or inflammatory disease were also excluded. Pain perception thresholds were assessed with a pressure algometer with digital traction and compression and a measuring capacity for 5 kg. All points were localized by palpation and marked with a felt-tipped pen and each individual was evaluated over a period of 2 days in two consecutive sessions, each session consisting of a set of 14 point measurements repeated twice by two examiners in random sequence. There was no statistically significant difference in the mean pain threshold obtained by the two examiners on 2 diferent days (examiner A: P = 1.00; examiner B: P = 0.75; Wilcoxon matched pairs test). There was excellent/good agreement between examiners for all days and all points. Our results have established baseline values to which future researchers will be able to refer. They show that pressure algometry is a reliable measure for pain perception in the abdominal wall of healthy women.