Beneficial effects of Ginkgo biloba extract on insulin signaling cascade,dyslipidemia, and body adiposity of diet-induced obese rats

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.     

Mental disorder: Are we moving away from distress and disability?

The first time that formally a definition of mental disorder was presented was in DSM‐III. This resulted from a complex conceptual analysis carried out by Spitzer, chair of the committee on nomenclature and statistics. The criteria of harm (distress‐disability) arise as main defining characteristics for mental illness, being added that “there is an inference” that there is a dysfunction. The distress‐disability model was later developed by Wakefield. This author argued that in a medical or psychiatric disorder there had to be a dysfunctional component (value free) and another one of harm (value laden). In this article, we intend to review the emergence and evolution of the definition of mental disorder and the importance that the criteria of distress and disability always had in this definition. This happened until the advent of DSM‐5 when these criteria came to play a secondary role.     

Excess weight and associated risk factors in patients with systemic lupus erythematosus

The objective of this study is to determine the socio-demographic, clinical and laboratory characteristics of outpatients with SLE who present with excess weight as well as to assess the immunosuppressive therapy used. One hundred and seventy women with SLE were evaluated consecutively in a transversal study. The relationship between excess weight and the patients’ characteristics was evaluated using univariate and multivariate Poisson regression analysis. Of the 170 patients evaluated, 109 presented with excess weight, two were malnourished and 59 were classified as eutrophic. Age and disease duration of those with excess weight were 42.4 ± 8.7 and 10.4 ± 6.2 years, respectively. Risk factors associated with excess weight were the following: age ≥40 years, <8 years of education, lack of occupation, damage index ≥1, systemic high blood pressure, diabetes mellitus and triglycerides ≥150 mg/dL levels. The use of antimalarial therapy and steroids was associated with a lower frequency of excess weight. Age ≥40 years and the non-usage of methotrexate were the variables independently associated with excess weight in the multivariate analysis. Patients with SLE who have excess weight present distinct clinical-laboratory findings, socio-demographic characteristics and treatment options when compared to normal weight patients. Prospective studies should assess whether these characteristics will interfere with the outcome or prognosis of lupus.     

Effects of the venom and the dermonecrotic toxin LiRecDT1 of Loxosceles intermedia in the rat liver

Brown spider bites cause dermonecrotic lesions and systemic manifestations known as loxoscelism. The Loxosceles intermedia venom contains many active proteins, as phospholipase D. There are reports of increased levels of hepatic transaminases in humans with loxoscelism, but detailed studies about the action of the Loxosceles intermedia venom on the liver functions are lacking. The aim of this study was to investigate the effects of the venom and the dermonecrotic recombinant toxin 1 (LiRecDT1) in the liver of Wistar rats injected subcutaneously with venom (80 μg) or toxin (80 μg). After 6 and 12 h the liver immunofluorescence was positive for venom and toxin. Hepatocytes from the venom group were tumefacted and apoptotic. There was leucocyte infiltration in the portal region combined with a high degree of steatosis in 12 h. In the toxin group the histological alterations were less severe. Plasma levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyl-transferase were significantly elevated only in the venom group in 6 h. Hepatic metabolism was modified: the venom, but not LiRecDT1, reduced gluconeogenesis and ureagenesis from alanine and glycogen accumulation. These results show that the venom is hepatotoxic and that the dermonecrotic toxin is only partly responsible.     

Essay on the epistemological relationship between probability and scientific method

In the XIX century, regularities in statistics of events were perceived in Medicine and Human Sciences. These regularities raised the possibility of forecasting what considered to be impredictable, and so, probabilistics laws became an alternative to the strictly-causal laws. This work presents a brief historical review of probability calculus and its applications. Some philosophical thoughs, regarding the use of probabilistics models and decision analysis in Medicine, are also discussed.     

Currarino triad: Characteristic appearances on magnetic resonance imaging and plain radiography

The Currarino triad is a complex anomaly consisting of an anorectal malformation, a sacral bone defect and a presacral mass. It was first described in 1981 and since then, approximately 250 cases have been reported. Radiology has an important part to play in the diagnosis of this entity, as the imaging features are characteristic. We report a case of Currarino triad in an infant who presented with intractable constipation and discuss relevant MRI and plain radiography findings.     

Management of Wilms' tumor with intracardiac extension

 We review our experience and the literature in treating 4 patients with Wilms' tumor (WT) with intracardiac extension among 92 patients with this neoplasm. Cardiopulmonary bypass with circulatory arrest and profound hypothermia was used. There were 3 boys (3 years, 4 years 5 months, and 15 years) and 1 girl (6 years). The follow-up periods were 8 months, 3 years, 2 years 6 months, and 15 years, respectively. We had no surgical complications and conclude that the preoperative diagnosis is extremely important. These patients must be transferred to institutions where concomitant cardiac procedures can be performed. In treating patients with WT, Doppler ultrasound must be used preoperatively in all cases, not only those in which clinical and radiologic signs of intravascular involvement are found. We propose that preoperative chemotherapy should be used, as it shrinks the thrombus and causes desirable adherence of the thrombus to the venous wall, reducing the probability of thromboembolism during the surgical procedure. We also find this method safer than in our 1st case, where neither cardiac arrest nor hypothermia was used. Our results agree with the literature that intracardiac extension of WT does not worsen its prognosis when a rational surgical approach is used. Accepted: 26 August 1999     

Loss of tumor-promoting activity of unleaded gasoline in N- nitrosodiethylamine-initiated ovariectomized B6C3F1 mouse liver

Unleaded gasoline (UG) vapor (2056 ppm) increased the incidence of liver tumors in a chronic bioassay and exhibited tumor-promoting activity in N-nitrosodiethylamine (DEN)-initiated female mouse liver. Estrogen inhibited mouse liver tumor development and the hepatocarcinogenic and tumor-promoting dose of UG produced uterine changes suggestive of estrogen antagonism. To directly test the hypothesis that UG-induced tumor-promoting ability is secondary to its interaction with the mouse liver tumor inhibitor, estrogen, we compared the tumor-promoting ability of UG in ovariectomized (Ovex) mice with the hepatic tumor-promoting ability of UG in intact mice. Ovaries were surgically removed at 4 weeks of age. Exposure to wholly vaporized UG (2018 ppm) under bioassay and tumor-promoting conditions began at 8 weeks of age. After 4 months of exposure, UG increased relative liver weight and hepatic microsomal cytochrome P450 pentoxyresourfin-O- dealkylase and ethoxyresorufin-O-deethylase activity to a similar extent in intact and Ovex mice. Non-focal hepatocyte proliferation, as measured by the incorporation of bromo-deoxyuridine, was not changed by UG exposure and was similar in all treatment groups. After 4 months of exposure to DEN-initiated mice, UG significantly increased the volume fraction of liver occupied by foci (three-fold) as compared to control intact mice. As expected, volume of foci was elevated in DEN/Ovex/control mice as compared to DEN/intact/control mice. In DEN/Ovex mice UG did not significantly increase the focal volume fraction. Thus, the tumor promoting activity of UG, as demonstrated by increased volume fraction of liver occupied by hepatic foci in intact mice, is greatly attenuated in Ovex mice. The volume fraction data in Ovex mice support the hypothesis that the tumor promoting activity of UG is dependent upon the interaction of UG with ovarian hormones. These data also indicate that hepatic microsomal cytochrome P450 PROD and EROD induction, hepatomegaly and non-focal hepatic LI are not specific markers of hepatic tumor promoting activity of UG.      

Prognostic indicators for breast cancer patients with one to three regional lymph node metastases, with special reference to alterations in expression levels of bcl-2, p53 and c-erbB-2 proteins

Patients with primary breast carcinoma with one to three axillary lymph node metastases but without distant metastases (n1-3) in Japan have been shown to have a 10-year disease-free survival rate of > 60%. It would be reasonable to divide n1-3 Japanese breast cancer patients into groups with high- or low-risk for recurrence and to consider post-operative adjuvant therapy. In the present study, we analyzed 228 consecutive Japanese patients with n1-3 breast cancer who underwent radical mastectomy and were followed up for a median time of 11.0 years. The expression of bcl-2, p53 and c-erbB-2 proteins in the primary tumors was examined immunohistochemically and their prognostic roles were also analyzed along with conventional clinicopathologic indicators. bcl-2 expression was correlated with positive estrogen receptor status and inversely correlated with p53, c-erbB-2 and histologic grade. Univariate analysis showed that bcl-2, p53 and c-erbB-2 expression were prognostic indicators of the patient's group as well as node status, histologic grade, tumor size, age at diagnosis, menopausal status and estrogen receptor status. Cox's regression analysis demonstrated that the number of nodes involved, menopausal status, p53 and bcl-2 were independent predictors for overall survival and that histologic grade and the number of nodes involved were independent predictors for disease-free survival. These results suggest that bcl-2 expression in combination with p53 and c-erbB-2 expression, the number of lymph node metastases, histologic grade and menopausal status are useful in selecting subgroups of n1-3 breast cancer patients with good or poor prognoses.