The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats

Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10 mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β₁ (TGF-β₁) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β₁, as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β₁ and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood.     

Distribution of Calcium, Iron, Copper, and Zinc in Two Portions of Placenta of Teenager and Adult Women

The placenta is fundamental for fetal development. The aim of this study was to determine Ca, Fe, Cu, and Zn content in the fetal and maternal portions of the placentas of teenage and adult women. Measurement of the minerals was conducted using Synchrotron radiation total reflection X-ray fluorescence. Forty samples from the fetal portion of teenagers and adults and 40 samples from the maternal portion of teenagers and adults were analyzed. There were significant differences in the Ca and Cu concentrations of the placenta's maternal portion when compared to the fetal portion, for both teenagers and adults. There were differences in Fe and Zn concentrations only when comparing the maternal portion of placenta with the fetal portion of the adults. These results suggest important differences in mineral content based on the placental portion. No significant difference was observed between the minerals studied of the maternal portion of teenagers and adults; however, in the fetal portion, mineral concentrations were greater in adults than in teenagers. Therefore, the mineral concentration of the fetal portion of the placenta is influenced by the mother's age. If there is mineral's competition between the mother and fetus during pregnancy in adolescence due to the importance of these minerals in growth and development, then the mechanism and reason for it should be elucidated in future research. In addition, we believe that further research should be carried out on transporters of these minerals in the same portions of the placentas analyzed by our group, in teenagers and adults.     

Outbreak of human herpesvirus type 1 infection in nonhuman primates (Callithrix penincillata)

Human herpesvirus type 1 (HHV-1) is widely dispersed among the human population. Although infection is often asymptomatic in humans, nonhuman primates develop a severe and often fatal infection. In August 2006, 13 black-tufted marmosets (Callithrix penincillata) from a group of 14 presented with clinical apathy, anorexia, and ataxia. Physical examination revealed conjunctivitis, erosive or ulcerative lesions on the skin, and swollen lymph nodes. Of the 14 animals captured, 10 died. Grossly, ulcers and erosions were observed on the skin of face, nasal planum, lips, and oral mucosa. Histologically, superficial vesicular and erosive stomatitis with associated basophilic intranuclear inclusion bodies in the squamous epithelium were observed. Swabs from oral lesions and tissue samples from necropsied animals were positive for HHV-1 by nested polymerase chain reaction for eight animals.     

Schistosoma mansoni: a method for inducing resistance to praziquantel using infected Biomphalaria glabrata snails

To elucidate the mechanisms of antischistosoma resistance, drug-resistant Schistosoma mansoni laboratory isolates are essential. We developed a new method for inducing resistance to praziquantel (PZQ) using successive drug treatments of Biomphalaria glabrata snails infected with S. mansoni. Infected B. glabrata were treated three times with 100 mg/kg PZQ for five consecutive days with a one-week interval between them. After the treatment, the cercariae (LE-PZQ) produced from these snails and the LE strains (susceptible) were used to infect mice. Forty-five days after infection, mice were treated with 200, 400 or 800 mg/kg PZQ. Thirty days post-treatment, we observed that the mean number of worms recovered by perfusion was significantly higher in the group of mice infected with the LE-PZQ isolate treated with 200 and 400 mg/kg in comparison to the LE strain with the same treatment. Moreover, there was a significant difference between the ED50 (effective dose required to kill 50% of the worms) of the LE-PZQ isolate (362 mg/kg) and the LE strain (68 mg/kg). In the in vitro assays, the worms of the LE-PZQ isolate were also less susceptible to PZQ. Thus, the use of infected snails as an experimental model for development of resistance to S. mansoni is effective, fast, simple and cheap.     

Intravenous rehydration for diarrheal dehydration of eutrophic children: survey of protocols provided at Colombian medical schools

Introduction. In all cases of severe dehydration from diarrhea, WHO recommends rapid rehydration. If oral rehydration in children is contraindicated, intravenous rehydration is recommended for immediate administration. However, methods of intravenous rehydration appear to be inadequately addressed in the medical schools of Colombia. Objective. Current approaches to oral rehydration were summarized, and instructors were informed concerning current WHO recommendations. Materials and methods. A survey was designed for pediatric instructors in Colombian medical schools. Direct questions about rehydration methods were included as well as presentation of theoretical clinical situations with dehydrated children. The survey also asked for the conditions necessary for intravenous rehydration and method of administration (volume, solution, concentration and speed of infusion). Results. Forty-one surveys were included (82% of medical schools in Colombia). Inadequate contraindications for oral rehydration therapy were made in 41%. Rapid and slow intravenous rehydration was recommended in 71% and 29%, respectively; 57% recommended fluid bolus to rehydrate. Adequate volumes were recommended by less than half of the respondents and adequate sodium concentration was recommended by 85%. In 56% of medical schools, glucose was not included in solutions and 66% use Ringer lactate. Normal saline solution, dextrose solution with electrolytes and polyelectrolytes solutions are also used. Conclusions. Misconceptions are common concerning the contraindications to oral rehydration therapy. One-third of medical schools promote a slow therapy despite the superiority of the rapid therapy. Uniformity for rapid therapy schemes is lacking. Bolus rehydration is commonly advocated despite the fact that this method is unsupported by the literature. Concepts about rehydration must be updated in medical schools and a national guide for intravenous rehydration is recommended.     

Laparoscopic ovum collection in sheep: gross and microscopic evaluation of the ovary and influence on ooctye production

Gross and microscopic evaluations of the ovaries of sheep subjected to successive ovum collection were performed with the objective of identifying if there was interference in oocyte production and morphology of gonads. Gross evaluation of the internal genital tract was also performed. Eighteen ewes of the Santa Inês breed were randomly distributed into three experimental groups of six animals each; G0, G1 and G9 with no, one and nine repetitions, respectively. Estrous synchronization was achieved with a short protocol using MAP followed by single dose stimulation with 80mg of FSHp and 300 IU of eCG (IM). Laparoscopic ovum pick-up was performed 36h later, with 7-day intervals. The number of visualized follicles, aspirated follicles and oocytes recovery was recorded. After the last intervention, ovariectomy was performed for evaluation of gross and microscopical appearance and existence of lesions caused by follicular puncture, which were classified as absent (0), mild (1), moderate (2) and severe (3). The number of visualized follicles, aspirated follicles and oocytes recovery were 13.2±2.0, 11.3±3.0 and 5.8±2.3, respectively, with a recovery rate of 51.7%. No statistical difference was found between the nine sessions (P>0.05). Nine sessions of superovulation and ovum collection procedures did not cause ovarian lesions and did not interfere with the production of follicles in ewes of the Santa Inês breed.     

Hesperidin,a Flavone Glycoside,as Mediator of Neuronal Survival

Flavonoids comprise the most common group of plant polyphenols and provide much of the flavor and color to fruits and vegetables. More than 5,000 different flavonoids have been described. The biological activities of flavonoids cover a very broad spectrum, from anticancer and antibacterial activities to inhibition of bone reabsorption and neuroprotection effect. Although emerging evidence suggests that flavonoids have an important role on brain development, little is known about their mechanisms of action. In the present work, we performed a screening of flavonoid actions by analyzing the effects of these substances (hesperidin and rutin) on neural progenitors and neuronal morphogenesis in vitro. We demonstrated that treatment of neural progenitors with the flavonoid hesperidin enhanced neuronal population as revealed by an 80% increase in the number of β-tubulin III cells. This effect was mainly due to modulation of neuronal progenitor survival. Pools of astrocyte and oligodendrocyte progenitors were not affected by hesperidin whereas rutin had no effect on neuronal population. We also demonstrated that the flavonoid hesperidin modulates neuronal cell death by activating MAPK and PI3K pathways. This opens the possibility of using flavonoids for potential new therapeutic strategies for neurodegenerative diseases.     

Characterization of novel StAR (steroidogenic acute regulatory protein) mutations causing non-classic lipoid adrenal hyperplasia

Context

Steroidogenic acute regulatory protein (StAR) is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH).

Objective

StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported.

Design

To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature.

Setting

Collaboration between the University Children''s Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d''Hebron, Autonomous University, Barcelona, Spain.

Patients

Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age.

Results

StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30%) and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol.

Conclusions

StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S) seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed.