Effects of mood stabilizers on hippocampus and amygdala BDNF levels in an animal model of mania induced by ouabain

There is a body of evidence suggesting that BDNF is involved in bipolar disorder (BD) pathogenesis. Intracerebroventricular (ICV) injection of ouabain (OUA), a specific Na⁺/K⁺ ATPase inhibitor, induces hyperlocomotion in rats, and has been used as an animal model of mania. The present study aims to investigate the effects of the lithium (Li) and valproate (VPT) in an animal model of mania induced by ouabain. In the reversal model, animals received a single ICV injection of OUA or cerebrospinal fluid (aCSF). From the day following the ICV injection, the rats were treated for 6 days with intraperitoneal (IP) injections of saline (SAL), Li or VPT twice a day. In the maintenance treatment (prevention model), the rats received IP injections of Li, VPT, or SAL twice a day for 12 days. In the 7th day of treatment the animals received a single ICV injection of either OUA or aCSF. After the ICV injection, the treatment with the mood stabilizers continued for more 6 days. Locomotor activity was measured using the open-field test and BDNF levels were measured in rat hippocampus and amygdala by sandwich-ELISA. Li and VPT reversed OUA-related hyperactive behavior in the open-field test in both experiments. OUA decreased BDNF levels in first and second experiments in hippocampus and amygdala and Li treatment, but not VPT reversed and prevented the impairment in BDNF expression after OUA administration in these cerebral areas. Our results suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.     

Health survey and assessment of the polymorphisms BRCA1/P871L,BRCA1/Q356R,and BRCA2/N372H in female gas station workers in Rio de Janeiro

Gas station workers are exposed to chemicals known to be carcinogenic, especially benzene. The objective was to analyze the health problems of female gas station workers by means of sociodemographic and clinical questionnaires, and laboratorial exams. We performed the genotyping of the polymorphisms BRCA1/P871L and BRCA1/Q356R by Polymerase Chain Reaction‐Restriction Fragment Length Polymorphism, and of variant allele BRCA2/N372H through direct sequencing. The female workers showed a higher concentration of monocytes (P = 0.039); a greater number of spontaneous abortions (P = 0.025, OR = 4.977, 95% CI = 1.135–30.669); higher tobacco consumption (P = 0.013); and higher alcohol consumption (P = 0.05). The statistical analysis of the polymorphisms associated with the variables monocyte concentration and miscarriage number did not reveal a significant relationship, and smoking and spontaneous abortion were not statistically associated either. Environ. Mol. Mutagen. 58:730–734, 2017. © 2017 Wiley Periodicals, Inc.     

Effect of erythromycin on gallbladder emptying in diabetic patients with and without autonomic neuropathy and high levels of motilin

A reduction of gallbladder emptying in response to neural or hormonal stimulation has been reported in patients with diabetes mellitus. Decreased gallbladder emptying may be a key factor in the pathogenesis of gallbladder stones. Few drugs, if any, are able to stimulate gallbladder emptying. However, in a previous study we demonstrated that erythromycin, a macrolide antibiotic, stimulates gallbladder emptying and motilin release in healthy human subjects by an atropine-sensitive pathway. Therefore, the present study was designed to evaluate the effect of erythromycin on gallbladder emptying and motilin release in diabetic patients with or without cardiac autonomic neuropathy (AN). Thirteen diabetic patients, six with AN, and 10 healthy subjects were enrolled in the study protocol. Gallbladder emptying was determined by sonography after ingestion of a standard meal and during infusion of erythromycin alone or together with 6 g/kg/hr atropine. We found that 100 mg/hr erythromycin caused a significant reduction in gallbladder volume in both healthy subjects and diabetic patients. The ejection fraction (mean ±se) of 45.3±8.2% and 37.3±5.0% was similar. The presence of AN had no influence on gallbladder emptying induced by erythromycin. Basal motilin plasma levels were 111.5±14.5 pmol/liter in diabetic patients and 63.3 ±6.0 pmol/liter in healthy subjects (P<0.01). However, patients with AN had higher (130.0 ±11.9 pmol/liter) motilin plasma levels than patients without (74.0±9.4 pmol/liter,P<0.01). Erythromycin administration caused an approximately twofold increase in plasma motilin concentrations in healthy subject and patients withou AN, but did not stimulate motilin release in neuropathic patients. A negative correlation (r=–0.75,P<0.01) was found between basal plasma levels of motilin and peak of gallbladder emptying induced by erythromycin. Atropine completely inhibited the effects of erythromycin on gallbladder emptying and motilin release (P<0.001 by ANOVA). A negative correlation (r=–0.52,P<0.05) was also found between plasma glucose concentrations and peak of gallbladder emptying. Present results demonstrate that erythromycin could be used for treating alterations of gallbladder emptying in diabetic patients with or without AN.     

Combination chemotherapy with mitomycin C,vindesine and melphalan for refractory metastatic breast cancer

Summary A combination of mitomycin C, vindesine and melphalan was administered to 33 patients with heavily pretreated refractory breast cancer. The overall response rate was 27% with a mean duration of more than 10.2 months. A stabilization with a mean duration of 5.1 months was seen in 56% of cases, while 20% of patients progressed. Gastrointestinal toxicity, mostly grade 1 or 2 nausea/vomiting was seen in 85% of cases, grade 1 or 2 leukopenia in 60% of patients, and grade 1 or 2 thrombocytopenia in 42%. Considering the good compliance of this regimen and the poor prognosis of patients with refractory advanced breast cancer, this combination can be useful as a palliative treatment of breast carcinoma.Abbreviations MMC mitomycin C - VDS vindesine - L-PAM melphalan     

Hb Southern Italy: coexistence of two missence mutations (the Hb Sun Prairie alpha2 130 Ala --> Pro and Hb Caserta alpha2 26 Ala --> Thr) in a single HBA2 gene

This study describes a new molecular condition in the alpha(2)-globin gene (HBA2) found in six unrelated families from Southern Italy (Campania and Sicily). This new double mutant form of haemoglobin is called Hb Southern Italy and originated from the coexistence of two known mutations occurring in the same globin gene, HBA2 26 G-->A (Hb Caserta) and HBA2 130 G-->C (Hb Sun Prairie). Hb Sun Prairie was originally observed in Indian patients in either the homozygous state, with severe hemolytic anemia, and in the heterozygous state with microcytosis, or in asymptomatic cases as an alpha-thalassemia carrier phenotype. Hb Caserta was observed for the first time in a Casertian family (South Italy) that displayed a slowmigrating haemoglobin upon investigation. We report the clinical phenotype and molecular study of this new double mutant form of haemoglobin in heterozygous and homozygous subjects, as well as in association with alpha degrees delectional thalassemia.     

Manometric patterns of rat colonic motor activity and defecation

We investigated in conscious and unrestrained rats, the major patterns of colonic pressure waves, as related to defecation. A manometric low compliance perfusion system, which was set at a very low flow rate (0.03 ml/min), permitted simultaneous recordings of intraluminal pressure in the proximal, transverse, and distal colon. Pressure waves in control rats reflected two types of motor activity: short-duration waves (<15 sec), that were frequent throughout the colon (about 40–90/hr with aborally decreasing frequency), and propulsive, long-duration, high-amplitude waves (>15 sec, >15 mm Hg) that occurred only occasionally (1/hr or less) in the transverse and distal, but not in the proximal colon; these waves appeared to migrate aborally and were associated with defection. The serotonin 5HT_1A agonist 8-OH-DPAT dramatically and dose-dependently increased the frequency of long-duration, high-amplitude waves in the transverse and distal colon, and concurrently promoted defecation; these effects were prevented by the putative 5HT_1A antagonist pindolol. We conclude that 5HT_1A agonists such as 8-OH-DPAT may promote defecation and occurrence of propulsive waves through the same serotoninergic mechanism.A preliminary account of this work was presented at the 13th International Symposium on Gastrointestinal Motility, Kobe, Japan, Abstract 172. J Gastrointest Motil 3, 1991.     

Galectina-3 Associada a Formas Graves e Mortalidade em Longo Prazo em Pacientes com Doença de Chagas

Background The histopathological characteristics of Chagas disease (ChD) are: presence of myocarditis, destruction of heart fibers, and myocardial fibrosis. Galectin-3 (Gal-3) is a biomarker involved in the mechanism of fibrosis and inflammation that may be useful for risk stratification of individuals with ChD.Objectives We sought to evaluate whether high Gal-3 levels are associated with severe forms of Chagas cardiomyopathy (CC) and whether they are predictive of mortality.Methods We studied anti-T. cruzi positive blood donors (BD): Non-CC-BD (187 BD without CC with normal electrocardiogram [ECG] and left ventricular ejection fraction [LVEF]); CC-Non-Dys-BD (46 BD with CC with abnormal ECG but normal LVEF); and 153 matched serum-negative controls. This cohort was composed of 97 patients with severe CC (CC-Dys). We used Kruskall-Wallis and Spearman’s correlation to test hypothesis of associations, assuming a two-tailed p<0.05 as significant.Results The Gal-3 level was 12.3 ng/mL for Non-CC-BD, 12.0 ng/mL for CC-Non-Dys-BD, 13.8 ng/mL for controls, and 15.4 ng/mL for CC-Dys. LVEF<50 was associated with higher Gal-3 levels (p=0.0001). In our linear regression adjusted model, we found association between Gal-3 levels and echocardiogram parameters in T. cruzi-seropositive subjects. In CC-Dys patients, we found a significant association of higher Gal-3 levels (≥15.3 ng/mL) and subsequent death or heart transplantation in a 5-year follow-up (Hazard ratio – HR 3.11; 95%CI 1.21–8.04; p=0.019).Conclusions In ChD patients, higher Gal-3 levels were significantly associated with severe forms of the disease and more long-term mortality, which means it may be a useful means to identify high-risk patients. (Arq Bras Cardiol. 2021; 116(2):248-256)     

Osteomuscular symptoms on motorcycles in the city of Rio Branco,Acre, Brazil,West Amazon

Musculoskeletal disorders gradually affect workers in different parts of the world, compromising their occupational health and quality of life. Professionals exposed to these symptoms include the motorcycle taxi driver, whose pain is due to the overuse of the musculoskeletal system and little time to recover it.To identify the prevalence of musculoskeletal symptoms in motorcycle taxi drivers in the city of Rio Branco, Acre, Brazil, West Amazon.Cross-sectional study, involving 296 motorcycle taxi drivers in the city of Rio Branco-Acre, Brazil, male, from December 2016 to February 2017. The Nordic Musculoskeletal Questionnaire was used to collect information related to symptoms (pain, discomfort, or numbness) in the last 7 days of work. For the exclusion criteria were, being female; not reside outside the city of Rio Branco, Acre; having less than 3 months of work activity; not be carrying out their work activities at the time of application of the protocol; be limited by clinical or physical issues at the time of application of the protocol. The data obtained in the questionnaire were entered into the Epidata program (Epidata Association, Odense, Denmark) and then transferred to the STATA 10 statistical program (Stata Corp., College Station), for categorization and statistical analysis.The study population is over 36 years old; most reported having a partner and a higher education level. The average daily working hours of the participants were 12 hours, with the majority working over 12 hours daily. Most of the epidemiological variables factors were associated with musculoskeletal pain when the prevalence and prevalence ratio analyzes were performed. Higher prevalence of musculoskeletal symptoms in the lumbar region is with 17.9%. In the lower limbs, the most affected joint was the ankle (5.7%), followed by the hip (5.07%) and knee (5.07%), respectively. Insomnia was present in 55.35% and self-reported headache in 49.4% of participants.The musculoskeletal disorders generated by the daily service of motorcycle taxi drivers are directly affecting the quality of life of these professionals.     

A Higher Angiogenin Expression is Associated With a Nonnuclear Maspin Location in Laryngeal Carcinoma

Objectives

In numerous malignancies, angiogenin (ANG) and Maspin are important proangiogenic and antiangiogenic regulators, respectively. The aim of this study was to identify potential relationships between the biological roles of these two proteins in laryngeal squamous cell carcinoma (LSCC).

Methods

Immunohistochemical staining for ANG and Maspin was performed on specimens from 76 consecutive LSCC patients treated with surgery alone, considering the subcellular pattern of Maspin expression. Univariate and multivariate statistical models were used for prognostic purposes.

Results

On univariate analysis, a different level of ANG expression was seen for patients stratified by subcellular Maspin expression pattern: the mean ANG expression was higher in cases with a nonnuclear MASPIN expression than in those with a nuclear pattern (P=0.002). Disease-free survival (DFS; in months) differed significantly when patients were stratified by N stage (P=0.01). Patients whose Maspin expression was nonnuclear (i.e., it was cytoplasmic or there was none) had a significantly higher recurrence rate (P<0.001), and shorter DFS (P=0.01) than those with a nuclear Maspin pattern. The mean ANG expression was significantly higher in cases with loco-regional recurrent disease (P=0.007); and patients with an ANG expression ≥5.0% had a significantly shorter DFS than those with an ANG expression <5.0% (P=0.007). On multivariate analysis, ANG expression ≥5.0% was a significant, independent, negative prognostic factor in terms of DFS (P=0.041).

Conclusion

Our results support the hypothesis that a higher ANG expression is associated with a nonnuclear Maspin expression pattern in patients with LSCC. Further studies are needed to clarify the relationship between the ANG and Maspin pathways, and their potential diagnostic and therapeutic role in LSCC.