Mice with impaired extrathyroidal thyroxine to 3,5,3'-triiodothyronine conversion maintain normal serum 3,5,3'-triiodothyronine concentrations

For T(3) to mediate its biological effects, the prohormone T(4) must be activated by removal of an outer-ring iodine by the type 1 or 2 deiodinases (D1 and D2) with approximately 60% of the daily T(3) production in rodents being produced extrathyroidally through this pathway. To further define the role of these enzymes in thyroid hormone homeostasis, we backcrossed the targeted disruption of the Dio2 gene into C3H/HeJ (C3H) mice with genetically low D1 expression to create the C3H-D2KO mouse. Remarkably, these mice maintain euthyroid serum T(3) levels with normal growth and no decrease in expression of hepatic T(3)-responsive genes. However, serum T(4) is increased 1.2-fold relative to the already elevated C3H levels, and serum TSH is increased 1.4-fold. Despite these increases, thyroidal (125)I uptake indicates no difference in thyroidal activity between C3H-D2KO and C3H mice. Although C3H-D2KO hepatic and renal D1 activities were well below those observed in wild-type mice (approximately 0.1-fold for both), they were 8-fold and 2-fold higher, respectively, relative to C3H mice. Thyroidal D1 and cerebral cortical type 3 deiodinase activity were unchanged between C3H-D2KO and C3H mice. In conclusion, C3H-D2KO mice have notably elevated serum T(4) levels, and this, in conjunction with residual D1 activity, is likely an important role in the maintenance of euthyroid serum T(3) concentrations.     

A diacylglycerol lipase-CB2 cannabinoid pathway regulates adult subventricular zone neurogenesis in an age-dependent manner

The subventricular zone (SVZ) is a major site of neurogenesis in the adult. We now show that ependymal and proliferating cells in the adult mouse SVZ express diacylglycerol lipases (DAGLs), enzymes that synthesise a CB1/CB2 cannabinoid receptor ligand. DAGL and CB2 antagonists inhibit the proliferation of cultured neural stem cells, and the proliferation of progenitor cells in young animals. Furthermore, CB2 agonists stimulate progenitor cell proliferation in vivo, with this effect being more pronounced in older animals. A similar response was seen with a fatty acid amide hydrolase (FAAH) inhibitor that limits degradation of endocannabinoids. The effects on proliferation were mirrored in changes in the number of neuroblasts migrating from the SVZ to the olfactory bulb (OB). In this context, CB2 antagonists reduced the number of newborn neurons appearing in the OB in the young adult animals while CB2 agonists stimulated this in older animals. These data identify CB2 receptor agonists and FAAH inhibitors as agents that can counteract the naturally observed decline in adult neurogenesis that is associated with ageing.     

Independent indicators of outcome in severe paediatric malaria: maternal education, acidotic breathing and convulsions on admission

Severe malaria is an important cause of death in hospitalized children in Mozambique, but the risk factors for this remain unclear. The objectives of the study were to define simple clinical criteria to identify on admission the children most at risk of dying. We studied prospectively 559 children admitted with severe malaria to the Department of Paediatrics of the Central Hospital of Maputo, Mozambique between March 1995 and August 1996. The case fatality rate was 3.6%. In a multiple logistic regression model, mothers' education (RR = 9.6, 95% CI 1.2-76.0), acidotic breathing (RR = 4.3, 95% CI 1.3-13.8) and convulsions in the emergency room (RR = 8.1, 95% CI 2.6-25.1) were associated with outcome. Together they predicted 97% of outcomes but only 33.3% of deaths.     

High prevalence of chronic pelvic pain in women in Ribeirão Preto, Brazil and direct association with abdominal surgery

INTRODUCTION:

Chronic pelvic pain is a disease that directly affects the social and professional lives of women.

OBJECTIVE:

To estimate the prevalence of this clinical condition and to identify independent factors associated with it in women living in Ribeirão Preto, Brazil.

METHODS:

A one-year cross-sectional study was conducted in a population sample of 1,278 women over the age of 14 years. The target population was predominantly composed of women who are treated by the public health system. The questionnaire was administered by interviewers who were not linked to the city health care programs. The prevalence of the morbidity was estimated. First, we identified the significant variables associated with pelvic pain (p<0.10) and then we attributed values of 0 or 1 to the absence or presence of these variables. Logistic regression analysis was used to identify and estimate the simultaneous impact of the independent variables. The results were expressed by odds ratio and their 95% confidence interval with p<0.05.

RESULTS:

The disease was found in 11.5% (147/1,278) of the sample. The independent predictors were dyspareunia, previous abdominal surgery, depression, dysmenorrhea, anxiety, current sexual activity, low back pain, constipation, urinary symptoms, and low educational level.

CONCLUSION:

The prevalence of chronic pelvic pain in Ribeirão Preto is high and is associated with conditions that can usually be prevented, controlled, or resolved by improvement of public health policies and public education.