Research Priorities and Methodological Implications

European Spine Journal - Best evidence synthesis. To report on gaps in the literature and make methodologic recommendations based on our review of the literature on frequency and risk factors,...     

A high-throughput approach towards a novel formulation of fenofibrate in omega-3 oil

A novel lipid formulation containing fenofibrate in omega-3 oil was developed using a novel high-throughput screening platform. The optimized formulation combines the cardiovascular health benefits from omega-3 oil with the potent lipid-regulating effect of fenofibrate. When tested against the current marketed product Tricor^® in healthy human volunteers, the new formulation was shown to be equivalent to Tricor^®.     

In vitro transformation of mouse mammary epithelial cells grown serum-free inside collagen gels

Mammary epithelial cells from 4-month-old virgin BALB/c mice were cultured inside collagen gels in the following serum-free media: Dulbecco's modified Eagle's medium:Hams's F-12 (1:1) supplemented with: insulin (10 micrograms/ml), bovine serum albumin (5 mg/ml), and epidermal growth factor (5 ng/ml); insulin, bovine serum albumin, progesterone (0.05 microgram/ml), and prolactin (1 microgram/ml); insulin, bovine serum albumin, progesterone, prolactin, and linoleic acid (10 micrograms/ml). Cells proliferated in all these media. The cells were treated with 0.01 micrograms/ml of 7,12-dimethylbenz(a)anthracene or 100 micrograms/ml of N-nitroso-N-methylurea on day 3 of culture and, subsequently, at 1-week intervals for 3-6 weeks. Tetradecanoylphorbol acetate (0.1 micrograms/ml) was added to selected cultures. The cultures were maintained for up to 9 weeks; the cells were then removed from the collagen gels, placed in monolayer culture for 2 days, and removed from monolayer culture, and 5 X 10(5) cells were transplanted to each of the gland-free mammary fat pads of 3-week-old female mice. Approximately 10 weeks after transplantation, the transplanted mammary fat pads were examined for outgrowths. Cells that were not treated with carcinogen and cultured for up to 9 weeks in different serum-free media and transplanted to the gland-free mammary fat pad produced only ductal outgrowths similar in morphology to the ducts of the virgin host's mammary glands. Six treatments with 7,12-dimethylbenz(a)anthracene, of cells grown in the presence of epidermal growth factor, induced 31% spindle cell tumors, 17% ductal hyperplasias, and 5% lobuloalveolar hyperplasias. Cells that were grown in epidermal growth factor and treated three times with N-nitroso-N-methylurea produced 23% ductal hyperplasias and 17% lobuloalveolar hyperplasias. Cells grown in the presence of progesterone and prolactin and treated three times with 7,12-dimethylbenz(a)anthracene produced up to 23% lobuloalveolar hyperplasias and 12% ductal hyperplasias. Three treatments with N-nitroso-N-methylurea of cells grown in progesterone- and prolactin-containing media produced a maximum of 50% lobuloalveolar hyperplasias and 33% ductal hyperplasias. The lobuloalveolar hyperplasias have the characteristics of the precancerous hyperplastic alveolar nodules found in mouse mammary tumorigenesis. The in vitro carcinogen-induced lobuloalveolar hyperplasias were transplantable, maintained their lobuloalveolar morphology in virgin hosts, and produced carcinomas.     

A new peritoneovenous shunt

For today's most common peritoneovenous shunt catheters, the high incidence of complications (disseminated intravascular coagulation [DIC], pulmonary problems, clotting of the intravascular end, and shunt kinking) results in limited use. We have designed a new peritoneovenous shunt catheter in which we improved mechanical biocompatibility with respect to both the peritoneum and the vasculature. The device consists of: a multimicroorifice ascites filter in a double-chambered collecting device, a tubular compression pump with an intratubular check-valve, and a check-valve catheter at the intravascular end for positive exclusion of blood by reflux or back diffusion. This configuration filters the proteinaceous material from the ascites fluid, transports the filtrate into the blood stream, maintains patency, act to prevent DIC by inhibiting the creation and transport of microthrombi into the cardiovascular system, and eliminates clot formation at the intravascular end.     

Treatment of Neck Pain: Noninvasive Interventions

European Spine Journal - Best evidence synthesis. To identify, critically appraise, and synthesize literature from 1980 through 2006 on noninvasive interventions for neck pain and its associated...     

Primary malignant melanoma of the esophagus with diffuse melanocytic atypia and melanoma in situ

Primary malignant melanoma is an unusual lesion in the esophagus that is not infrequently seen in association with melanosis. A case of esophageal invasive malignant melanoma with melanosis is described in which the melanosis exhibited melanocytic atypia extending through to melanoma in situ. The authors know of no previously reported such finding.     

Hepatic oxidative stress following prolonged sublethal microcystin LR exposure.

Microcystin LR (MCLR) is a naturally occurring protein phosphatase inhibitor and potent hepatotoxin produced by strains of Microcystis aeruginosa. Although its acute toxicity has been well characterized, little is known about its chronic effects. In this study, we sought to acquire evidence that oxidative stress may play a role in the pathogenesis of prolonged sublethal MCLR toxicity. Twelve rats (3 per group) weighing on average 185 g were exposed to 1 of 3 different concentrations of MCLR (16, 32, and 48 microg/kg/day) or to saline via intraperitoneal osmotic pumps for 28 days. Histologic evidence of dose-dependent hepatic inflammation was seen, including infiltration of centrilobular regions by lymphocytes, macrophages, and neutrophils, centrilobular fibrosis, apoptosis, and steatosis. Analysis of lipid peroxidation products revealed a dose-dependent increase in malondialdehyde concentrations with an approximate 4-fold increase in the livers of the high-dose rats over those of the saline-treated controls. Livers from MCLR-exposed rats were more sensitive than those of controls to the cytotoxic effects of the organic oxidizing agent tert-butyl hydroperoxide, based on an MTT (3-[dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) viability assay. These histopathologic and biochemical findings indicate that oxidative stress may play a significant role in the pathogenesis of chronic MCLR toxicosis.