Barbiturate resuscitation from focal cerebral ischemia — A review

Barbiturate therapy has been shown to be of benefit in certain instances for focal cerebral ischemia. This therapy can, however, result in a deleterious outcome. Early institution in combination with revascularization appears to be important for successful barbiturate application. Whether combinations of agents designed to act on different mechanisms in the pathophysiology of cerebral ischemia can prolong the ‘therapeutic window’ of barbiturate application is an area for future investigation.     

Energy expenditure of calorically restricted rats is higher than predicted from their altered body composition

Debate exists over the impact of caloric restriction (CR) on the level of energy expenditure. At the whole animal level, CR decreases metabolic rates but in parallel body mass also declines. The question arises whether the reduction in metabolism is greater, smaller or not different from the expectation based on body mass change alone. Answers to this question depend on how metabolic rate is normalized and it has recently been suggested that this issue can only be resolved through detailed morphological investigation. Added to this issue is the problem of how appropriate the resting energy expenditure is to characterize metabolic events relating to aging phenomena. We measured the daily energy demands of young and old rats under ad libitum (AD) food intake or 40% CR, using the doubly labeled water (DLW) method and made detailed morphological examination of individuals, including 21 different body components. Whole body energy demands of CR rats were lower than AD rats, but the extent of this difference was much less than expected from the degree of caloric restriction, consistent with other studies using the DLW method on CR animals. Using multiple regression and multivariate data reduction methods we built two empirical predictive models of the association between daily energy demands and body composition using the ad lib animals. We then predicted the expected energy expenditures of the CR animals based on their altered morphology and compared these predictions to the observed daily energy demands. Independent of how we constructed the prediction, young and old rats under CR expended 30 and 50% more energy, respectively, than the prediction from their altered body composition. This effect is consistent with recent intra-specific observations of positive associations between energy metabolism and lifespan and theoretical ideas about mechanisms underpinning the relationship between oxygen consumption and reactive oxygen species production in mitochondria.     

Idiopathic pulmonary fibrosis: misunderstandings between epithelial cells and fibroblasts?

Idiopathic pulmonary fibrosis is a complex disease of unknown etiology which produces a progressive and irreversible destruction of the alveolar-capillary units leading ultimately to death from respiratory failure. For a long time the pathogenesis of the disease was attributed to an unresolved chronic alveolitis. However, a growing body of evidence suggests that inflammation does not play a major role in this disease, and that the pivotal pathogenic mechanisms include epithelial cell microinjuries/activation, and fibroblast migration, proliferation, and differentiation in myofibroblasts forming discrete foci in the injured areas. Active fibroblasts/myofibroblasts from these foci may in turn disturb alveolar re-epithelialization, by provoking basement membrane disruption and epithelial cell apoptosis finally resulting in exaggerated extracellular matrix accumulation. This aberrant repair process annihilates the lung architecture leading to the honeycomb remodeling.     

Surgical management of recurrent cervical cancer

The majority of patients with recurrent cervical cancer are incurable and treatment is based on the type of primary therapy delivered. Only a very small percentage of the patients with recurrent cervical cancer following primary radiotherapy will have central pelvic recurrences that are amenable to surgical resection and curable by pelvic exenteration. These procedures should be undertaken only after the completion of exhaustive attempts to exclude extrapelvic disease.     

Successful pregnancies and deliveries after a simple vitrification protocol for day 3 human embryos

OBJECTIVE: To evaluate the efficacy and efficiency of freezing cleaved human embryos through vitrification. DESIGN: Clinical study of vitrification of human embryos. SETTING: Assisted reproductive technology centers. PATIENT(S): Thirty-six patients undergoing IVF-ICSI treatment whose surplus embryos were frozen. INTERVENTION(S): Two hundred fifteen surplus embryos vitrified, subsequently thawed, and transferred in natural or controlled cycles. MAIN OUTCOME MEASURE(S): Embryo survival rate after thawing and resultant patient pregnancy rate. RESULT(S): From the 215 vitrified and thawed embryos, 106 survived, with an overall embryo survival rate of 49.3%. The survival rate was higher when embryos were vitrified at the eight-cell stage compared with at the six to seven-cell and six-cell stages (79.2%, 39.7%, and 21.1%, respectively). On average, 2.9 +/- 1.2 embryos per patient were transferred, resulting in 11 pregnancies (30.5%), with an implantation rate of 10.4% per embryo transferred. CONCLUSION(S): Ultrarapid embryo freezing by vitrification of eight-cell stage embryos is a reliable method, as evidenced by high rates of embryo survival and pregnancy, making it a superior alternative to the conventional slow-cooling method.     

Matrix metalloproteinases inhibition attenuates tobacco smoke-induced emphysema in Guinea pigs

STUDY OBJECTIVE: To evaluate the effect of CP-471,474 (Pfizer Global Research and Development; Groton, CT), a broad-spectrum inhibitor of matrix metalloproteinases (MMPs) in an experimental model of emphysema. DESIGN: Randomized, double-blinded, controlled experiment. SETTING: Biochemistry and morphology laboratories and animal research facility. METHODS: Guinea pigs were exposed to cigarette smoke over 1 month, 2 months, and 4 months, and half of the animals received CP-471,474. Age-matched guinea pigs exposed to room air were used as control animals. After death, the lungs were lavaged with saline solution, and MMPs in the lavage fluid were determined by zymography and immunoblot. Lungs were fixed for histology, immunohistochemistry, and morphometry. RESULTS: Following a 1-month exposure to tobacco smoke, semiquantitative histologic assessment showed moderate lung inflammation, which progressed in extent and severity and reached a peak at 2 months. CP-471,474 significantly reduced both the extent (p < 0.002) and severity (p < 0.05) of inflammation at 2 months. At 4 months, a spontaneous reduction of the inflammatory response was observed in both treated and untreated animals, and consequently no difference was observed between both. Emphysematous changes, revealed by a significant increase in the average size of alveoli, were detected at 2 months and 4 months of tobacco smoke exposure. The inhibitor significantly decreased the destructive lesions mainly at 2 months (p < 0.0001) and also at 4 months (p < 0.02). Smoking increased MMP-9 and MMP-1 activities as shown by zymography and immunoblot. Immunoreactive MMP-9 was mainly localized in alveolar and bronchiolar epithelial cells, macrophages, and airways smooth-muscle cells. CONCLUSION: These findings support a role for MMPs in the early inflammatory response and in the emphysematous lesions provoked by cigarette smoking.