Maximal lactate steady state does not correspond to a complete physiological steady state

The purpose of this study was to verify whether the maximal lactate steady state (MLSS) corresponds to a physiological steady state. Eight male trained subjects performed a 30-min test on a cycle ergometer at a constant power corresponding to their own MLSS which had been previously determined. No significant variation was observed between the 10th and the 30th min for arterial lactate concentration, redox state, arterial oxygen pressure, arterial oxygen saturation, bicarbonates concentration, base excess, hematocrit, hemoglobin concentration, plasma volume, oxygen uptake, carbon dioxide output, gas exchange ratio, minute ventilation, ventilatory equivalents for oxygen and carbon dioxide, and arterial systolic blood pressure values. However, arterial carbon dioxide pressure and pH values were significantly different between the 10th and the 30th min (p < 0.01). Respiratory rate values and heart rate significantly increased (p < 0.01). These results indicate that MLSS does not correspond to a complete physiological steady state.     

The association between socio-demographic factors and leisure-time physical activity in the Pró-Saúde Study

This study evaluated the relationship between socio-demographic variables and leisure-time physical activity (LTPA). A baseline survey questionnaire was completed by 4,030 employees. LPTA was assessed as engagement in physical activities during the previous two weeks. The metabolic cost of LTPA was calculated based on frequency and amount of time participating in physical activities, assigning weekly metabolic equivalents (METs) to each activity. Odds ratios (OR) to express the relationship between socio-demographic factors and LTPA were estimated from multinomial regression models. The questions used to evaluate LTPA presented moderate reproducibility, with kappa correlation coefficients ranging from 0.45 to 0.88. Prevalence of LTPA was higher among men (52.2% men; 40.8% women). For both men and women, higher educational level and higher income were both associated with engaging in LPTA, this relationship being stronger for the highest tercile of METs as compared to physical inactivity. Men were more engaged in LTPA, and there was a strong association between LTPA and socio-demographic variables for both genders.     

A role for corticotropin releasing factor (CRF) in ethanol consumption,sensitivity, and reward as revealed by CRF-deficient mice

Abstract Rationale. The alcohol discriminative stimulus has been extensively studied in animals and demonstrated to be pharmacologically complex. In contrast, however, the alcohol stimulus has been less frequently studied in humans. Objectives. The aim of the experiments reported here was to characterise pharmacologically an alcohol discriminative stimulus in social drinkers. Methods. Volunteers were first trained to discriminate a dose of 0.2 g/kg alcohol from placebo, using an established method. We then investigated the generalisation response and subjective effects following a range of doses of the γ-amino-butyric acid (GABA)_A benzodiazepine-receptor agonist lorazepam (0, 0.5, 1 and 2 mg, PO). Results. Low doses of lorazepam (0.5 and 1 mg) did not cross-generalise with the alcohol stimulus and produced only minimal subjective effects. However, a dose of 2 mg lorazepam substituted (60.8%) for the stimulus (P<0.02) and increased subjective ratings of "lightheaded" (P<0.05). Conclusions. These results are consistent with the pre-clinical literature and indicate the cross-species generality of the GABA_A component of the alcohol discriminative stimulus. Electronic Publication     

Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV-1

IntroductionErectile dysfunction (ED) is associated with neurological damage due to human T-lymphotropic virus 1 (HTLV-1) infection, but hormonal and psychogenic factors also cause ED.AimTo evaluate the association of psychogenic and hormonal factors with ED in men infected with HTLV-1.MethodsIn this cross-sectional study, we compared total testosterone, follicle stimulating hormone, luteinizing hormone, prolactin, anxiety symptoms, depressive symptoms, and neurologic manifestations in HTLV-1-infected men with or without ED. The International Index of Erectile Function was used to determine the degree of ED. Participants were grouped according to Osame’s Motor Disability Scale and the Expanded Disability Status Scale: HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP), probable HAM/TSP, or HTLV-1 carrier. Chi-square and Fisher’s exact tests were used to compare the groups, and regression analyses were used to show predictors of ED.Main Outcome MeasureSexual hormonal levels, psychogenic factors, and neurologic disabilities were found to be associated with ED.ResultsED was associated with age older than 60 years (P < .001), degree of neurologic involvement (P < .001), depression (P = .009), and anxiety (P = .008). In the multivariate analyses, only age and degree of neurological injury remained as risk factors for ED.Clinical ImplicationsNeurological manifestations are a stronger predictor of ED than hormonal and psychogenic factors in HTLV-1-infected men.Strengths & LimitationsThe statistical power of the study was limited due to the low number of participants, but neurologic manifestations were clearly associated with ED. There was no strong association between hormonal and psychogenic factors and ED.ConclusionHormonal and psychogenic factors did not show a strong association with ED in individuals with HTLV-1, but neurological manifestations were strongly associated with ED in these individuals.de Oliveira CJV, Neto, JAC, Andrade RCP, et al. Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV–1. J Sex Med 2019; 16:1763–1768.     

Association between the HLA-G molecule and lymph node metastasis in papillary thyroid cancer

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and can present as lymph node metastasis in 30 to 65% of cases when initially diagnosed. High frequency recurrence, distant metastasis and treatment resistance can be found in cases of PTC so early diagnosis and treatment are critical for improved prognosis and better survival rates. The characterization of new biomarkers has proved useful for the diagnosis and follow-up of these patients. HLA-G is a non-classical HLA class I molecule whose expression in cancer cells has been associated with tumor evasion of immune response. Therefore, the aim of this study was to investigate the HLA-G expression and its clinical significance in PTC. Paraffin-embedded thyroid biopsies of 70 PTC patients (40 of whom had presented with metastasis) were evaluated. HLA-G-staining was observed in tumor cells in PTC, and the HLA-G expression was significantly associated with an increased occurrence of lymph node metastasis (p = 0.0006) and capsular invasion (p = 0.02). This preliminary data shows the HLA-G expression in thyroid carcinoma specimens for the first time and suggests that this expression could impair efficient anti-tumor immunity in PTC. This would indicate that HLA-G could have an independent prognostic value in PTC, principally for tumor recurrence.     

Cushing's disease in a 5-month infant due to a basophilic microadenoma of the pituitary gland

We report a female patient who developed severe Cushing's disease during the fifth month of life due to a basophilic pituitary adenoma Histological findings showed a basophilic microadenoma of the pituitary gland, leading to the diagnosis of Cushing's disease. The infant died because of untreatable septic shock. The importance of the present report resides in the age of the child at diagnosis, and that it was the necropsy finding of microadenoma which clarified the cause of the Cushing's syndrome, since it was not diagnosed during life. Cushing's disease is most often diagnosed in children older than 7 years, and our patient was only 5 months old when we detected the pituitary adenoma, the earliest case diagnosed so far. Cushing's syndrome in pediatric patients has been rarely reported and most cases are due to functioning adrenal tumors, usually a malignant carcinoma but occasionally a benign adenoma. The present case shows that the pituitary of these patients should be investigated with important implications in terms of therapeutic approaches, such as pituitary radiotherapy, which can cure the patient when treatment is started very soon.     

Agreement among insulin sensitivity indexes on the diagnosis of insulin resistance in polycystic ovary syndrome and ovulatory women

OBJECTIVE: The objective was to compare agreement on the diagnosis of insulin resistance (IR) among insulin sensitivity indexes in both ovulatory women and those with polycystic ovary syndrome (PCOS). STUDY DESIGN: In an observational study, the 75-g oral glucose tolerance test was performed in 105 women with PCOS and 51 ovulatory women. The insulin sensitivity indexes used were insulin quantitative sensitivity check index (QUICKI), 1/homeostasis model assessment-insulin resistance (1/HOMA-IR), area under curve for insulin (AUC-I), and the Matsuda insulin sensitivity index (COMP). For the IR diagnosis we used cut-off values described in recent publications (insulin >12 microIU/ml, 1/HOMA-IR <0.47, QUICKI < or =0.333, AUC-I > or =7000 microIU/ml 120 min, and COMP <4.75. RESULTS: Excellent agreement was assessed among insulin, QUICKI, and 1/HOMA-IR. However, the rate of IR detected by these indexes in the PCOS group (44.8-51.4%) was lower than expected. New cut-offs were then determined based on COMP results. Using these values, 1/HOMA-IR and QUICKI showed excellent agreement (kappa=0.83) with COMP. CONCLUSION: The observed agreements among insulin, QUICKI and 1/HOMA-IR were higher than 93%. Therefore, clinicians may choose any of those obtaining similar results. For clinicians who prefer COMP, but are looking for a simpler test to detect IR in PCOS women, the use of QUICKI and 1/HOMA-IR with the new cut-offs seems reasonable.     

Endometrial thickness and volume by three-dimensional ultrasound one week after embryo transfer to detect pregnancy

Purpose: Determine if the evaluation of endometrium one week after embryo transfer can predict pregnancy. Methods: Endometrial volume and thickness were evaluated by three-dimensional ultrasound in 40 patients one week after embryo transfer. These results were compared to serum pregnancy test performed one week later. Results: Eighteen patients have achieved pregnancy. A significant difference was found for endometrial volume: 6.49±1.97 mL versus 3.40±1.11 mL (pregnant versus not pregnant); and thickness: 11.15±2.75 mm versus 9.77±1.85 mm. The ROC curve was used to detect the best cutoff values: endometrial volume of 3.48 mL (sensitivity-100%, specificity-68.2%) and endometrial thickness of 10.3 mm (sensitivity-72.2%, specificity-77.3%). The area under curve was significant higher for endometrial volume (0.909 versus 0.745, p=0.027). No pregnancy was achieved in women who had an endometrial volume <3.8 mL (15 patients) or thickness <7.9 mm (3 patients). Conclusions: The endometrial volume and thickness were significant higher in pregnant women and this difference was more prominent for endometrial volume.     

Gonadal function in adolescent patients submitted to chemotherapy during childhood or during the pubertal period

STUDY OBJECTIVE: To determine the presence of impaired gonadal function in adolescent patients submitted to chemotherapy during childhood or during the pubertal period. DESIGN: A case series study of 28 patients aged 12 to 19 years with menarche at least 2 years before the study. SETTING: Tertiary care public hospital. PARTICIPANTS: Group I: 14 adolescents previously submitted to chemotherapy during the prepubertal or peripubertal period and with remission of oncologic disease for at least 2 years; Group II: 14 normal adolescents with no previous oncologic disease and with regular menstrual cycles. INTERVENTIONS AND MAIN OUTCOME MEASURES: Pubertal development, menstrual cycles and serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined during the early follicular phase. RESULTS: There were no differences between the two groups in terms of age at appearance of secondary sexual characteristics or age at menarche. Menstrual irregularity was detected in 7 of the 14 patients in Group I, all 8 of whom presented oligomenorrhea. There were no differences in LH levels between the two groups (P = 0.55), although mean FSH levels were higher in Group I than in Group II (6.71 +/- 2.99 mIU/ml vs. 3.83 +/- 2.01 mIU/ml, P = 0.01). CONCLUSION: Although girls submitted to chemotherapy during the prepubertal or peripubertal period presented normal sexual development, the incidence of oligomenorrhea was higher than expected for their age, and FSH levels, although within normal limits, were higher than those seen in normally cycling girls.     

New perspectives for chronic pain treatment: a patent review (2010-2016)

Introduction: Chronic pain is a major problem of public health worldwide and is responsible for the increase in health costs. The therapeutic options available in the market for the treatment of chronic pain are often rather ineffective due to; the high number of adverse reactions, tolerance and dependence, reducing the quality of life, pharmacotherapy adherence and functional capacity. Hence, several studies have been conducted in the search for new treatment alternatives for chronic pain syndromes.

Areas covered: This review brings together the therapeutic patents published over the past six years reporting the discovery of new drugs for the treatment of chronic pain, based on the perspective that these compounds are candidates for the management of chronic pain conditions.

Expert opinion: Over the past 6 years, several pharmaceutical companies, as well as universities and researchers, have synthesized a series of compounds, which have been shown to be effective in controlling chronic pain in preclinical studies. These findings nurture the hope of discovering new therapeutic options for chronic pain. However, such studies are in early stages and there is a long and hard path to be followed until these compounds can become chemical entities available to the public.