Levodopa-induced hyperactivity in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

The present study examines the motor responses of 10- to 12-month-old, male C57 mice that were either given intraperitoneal (IP) injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg per day) or vehicle for 10 consecutive days, followed by IP injections of levodopa (200 mg/kg) plus carbidopa (25 mg/kg). Five days of MPTP exposure resulted in the Straub tail phenomenon and pronounced hypokinesia. However, during the next 5 days, motor activity returned to baseline, even with continued MPTP treatment. After 10 to 14 days of rest, all mice were then treated with levodopa/carbidopa twice daily for multiple, consecutive days. However, only the previously MPTP-treated animals became hyperkinetic, as compared to levodopa-treated control animals that were not previously exposed to MPTP. Abnormal activity included scratching, running, gnawing, and jumping movements. Hyperactivity lasted for approximately 2 hours after each levodopa injection and then returned to baseline, but the amount of hyperkinesia increased with additional days of levodopa treatment, even though the daily levodopa dose was not changed. These results demonstrate that levodopa can cause reproducible hyperactivity in mice that were previously exposed to MPTP.     

Laparoscopic cholecystectomy in a patient with a biventricular cardiac assist device.

Evaluation and management of abdominal pathology in patients with ventricular assist devices is likely to become increasingly important as the utilization of these devices expands. Ventricular assist devices represent a class of intracorporeal or paracorporeal mechanical devices that augment cardiac output in patients with congestive heart failure. Patients with ventricular assist devices supporting both right and left ventricles (biventricular assist devices) are uniquely challenging to the general surgeon because these devices restrict direct access to the abdominal cavity and because of the perioperative implications of biventricular heart failure. We describe herein the first reported successful laparoscopic cholecystectomy in a patient with a paracorporeal biventricular assist device. Cholecystectomy was performed in this patient for acute cholecystitis that occurred while the patient was awaiting heart transplantation. Our results add weight to the small body of evidence that laparoscopy is well tolerated in ventricular assist devices patients. The unique aspects of the biventricular assist device patient make laparoscopic abdominal intervention particularly suitable in this patient population.     

Dietary selenium's protective effects against methylmercury toxicity

Dietary selenium (Se) status is inversely related to vulnerability to methylmercury (MeHg) toxicity. Mercury exposures that are uniformly neurotoxic and lethal among animals fed low dietary Se are far less serious among those with normal Se intakes and are without observable consequences in those fed Se-enriched diets. Although these effects have been known since 1967, they have only lately become well understood. Recent studies have shown that Se-enriched diets not only prevent MeHg toxicity, but can also rapidly reverse some of its most severe symptoms. It is now understood that MeHg is a highly specific, irreversible inhibitor of Se-dependent enzymes (selenoenzymes). Selenoenzymes are required to prevent and reverse oxidative damage throughout the body, particularly in the brain and neuroendocrine tissues. Inhibition of selenoenzyme activities in these vulnerable tissues appears to be the proximal cause of the pathological effects known to accompany MeHg toxicity. Because Hg's binding affinities for Se are up to a million times higher than for sulfur, its second-best binding partner, MeHg inexorably sequesters Se, directly impairing selenoenzyme activities and their synthesis. This may explain why studies of maternal populations exposed to foods that contain Hg in molar excess of Se, such as shark or pilot whale meats, have found adverse child outcomes, but studies of populations exposed to MeHg by eating Se-rich ocean fish observe improved child IQs instead of harm. However, since the Se contents of freshwater fish are dependent on local soil Se status, fish with high MeHg from regions with poor Se availability may be cause for concern. Further studies of these relationships are needed to assist regulatory agencies in protecting and improving child health.     

A study of the freeze-drying conditions of calixarene based solid lipid nanoparticles.

In this note, we report a study of cryoprotectant carbohydrate (glucose, fructose, mannose and maltose) effects on the reconstitution of calixarene based solid lipid nanoparticle (SLN) suspensions after freeze-drying, studied by atomic force microscopy and photon correlation spectroscopy. All carbohydrates tested showed excellent cryoprotection and redispersion properties with the calixarene based SLNs.     

The human CD40 gene lies within chromosome 20q deletions associated with myeloid malignancies

Deletions of chromosome 20q are associated with myeloid malignancies and have been previously shown to arise in a multipotent progenitor of both myeloid and B cells. However, B-cell differentiation from the abnormal progenitor was impaired. The CD40 antigen is a surface glycoprotein which is expressed in B cells and haemopoietic stem cells and is important for B-cell growth and development. Following the recent mapping of CD40 to chromosome 20q we sought to determine its position relative to 20q deletions. Analysis of lymphoblastoid cell lines carrying 20q deletions placed CD40 within a 19–21 cM interval which is almost coincidental with the common deleted region defined by previous analysis of patient samples. Our results raise the possibility that genetic alteration of this locus may contribute to the pathogenesis of myeloid disorders associated with 20q deletions.     

Epidemiologists in the United States: an assessment of the current supply and the anticipated need

We provide 1985 estimates of the work force of epidemiologists in the United States, the number of graduates from training programs in epidemiology, and a projection of the future need for these health professionals. Our methods included a search of mailing lists from professional organizations, mail contact with graduate training programs, telephone interviews with experts, and a review of job announcements in professional journals. The study indicates that the current work force of epidemiologists in the United States is estimated to include 4,600 persons, more than half of whom are physicians; most epidemiologists are located in either a state with a major federal public health agency or one with a large population; and programs in epidemiology graduate an average of 475 persons with one or two years of master's level education and approximately 80 with doctoral-level education each year. After considering the factors that influence the supply of epidemiologists, we project a substantial need for more epidemiologists in the future than current sources will provide.     

Asbestos bodies in lung tissue following exposure to crocidolite

A series of 206 necropsies in Western Australia (WA) have had routine counts made of asbestos bodies in samples of lung tissue using conventional light microscopy. Thirty-two cases had worked in the asbestos industry at Wittenoom, WA and (log) counts of asbestos bodies in their lung tissue correlated well with estimates of their (log) cumulative airborne exposure to crocidolite fibers (r = 0.60). There was no association between the number of asbestos bodies and time since exposure to asbestos ceased. In subjects without known exposure to asbestos, there was a weak but nonsignificant increase in number of asbestos bodies with increasing age, with 26% of cases having no asbestos bodies present. It is concluded that the relatively simple technique of light microscopy for counting of asbestos bodies in lung tissue provides a reliable indication of the level of past occupational exposure to crocidolite in subjects whose exposure has been only to crocidolite. This could be extremely useful in follow-up studies of cohorts that lack reliable measures of airborne exposure to crocidolite asbestos.