A vaccinia-vectored rabies vaccine field trial: ante- and post-mortem biomarkers

During the field safety evaluation of a vaccinia-rabies glycoprotein recombinant virus vaccine for wildlife, two biomarkers were used to identify potential contact with vaccine-laden baits. Tetracycline, a commonly used and reliable calciphilic tissue marker, was included in a fish-meal polymer bait matrix and was evaluated from post-mortem bone samples. Additionally, an ante-mortem marker was needed to identify, for prospective study, raccoons which had contacted baits and thus, potentially, vaccine. Sulfadimethoxine (SDM) was included in an attractant slurry surrounding the bait, as a novel short-term seromarker. Preliminary laboratory studies in raccoons demonstrated SDM residues for up to one week following ingestion of a single 250 mg dose. During the first six days after bait distribution, 49 individual raccoons were live-trapped in the vaccination area. SDM was detectable in 38 of 49 (77.5%) serum samples. Similarly, 47 of 56 (83.9%) bone samples from raccoons collected in the vaccination area throughout the twelve-month study were tetracycline-positive. Conversely, none of the serum samples (n = 12) from the first six days of the trial nor any of the bone samples (n = 34) from raccoons in the surveillance area were biomarker-positive.     

Are somatic cells inherently deficient in methylation metabolism? A proposed mechanism for DNA methylation loss, senescence and aging

A mechanism of aging is proposed for mammals and other vertebrates. In this mechanism, most somatic cells have inherent deficiencies in methylation metabolism with respect to their capacity to methylate DNA. This leads to incomplete DNA methylation in each cell cycle which, accumulated over many cell cycles, contributes to genetic instability, senescence and cancer. These proposed metabolic deficiencies are present from the time somatic cells are young, yet it is only after many cell divisions that deleterious effects are realized. In nature, most animals have reproduced or have been killed by predators or other environmental hazards before they can be greatly affected by these deficiencies. These deficiencies evolved in animals eating a balance of nutrients from nature. Evidence from the literature is reviewed which establishes that methylation is lost from the DNA of many mammalian somatic cells as they age both in vivo and in vitro, and that DNA methylation levels are influenced by factors, such as diet, that affect methylation metabolism. Partially correcting the proposed deficiencies is considered as a possible molecular mechanism by which caloric restriction extends lifespan. Other possible dietary and transgenic means to correct the proposed deficiencies and extend lifespan are discussed.     

Lead suppresses chimeric human transferrin gene expression in transgenic mouse liver

The major iron-transport protein in serum is transferrin (TF) which also has the capacity to transport other metals. This report presents evidence that synthesis of human TF can be regulated by the metal lead. Transgenic mice carrying chimeric human TF-chloramphenicol acetyl transferase (CAT) genes received lead or sodium salts by intraperitoneal injections or in drinking water. Transgene expression in liver was suppressed 31 to 50% by the lead treatment. Lead regulates human TF transgenes at the mRNA level since liver CAT enzyme activity, CAT protein, and TF-CAT mRNA levels were all suppressed. The dosages of lead did not alter synthesis of the other liver proteins, mouse TF and albumin, as measured by Northern blot analysis of total liver RNA and rocket immunoelectrophoresis of mouse sera. Moderate levels of lead exposure were sufficient to evoke the human TF transgene response; blood lead levels in mice that received lead acetate in drinking water ranged from 30 micrograms/dl to 56 micrograms/dl. In addition to suppressing expression of TF-CAT genes in transgenic mice, lead also suppressed synthesis of TF protein in cultured human hepatoma HepG2 cells. The regulation of human TF apparently differs from the regulation of mouse TF which is unresponsive to lead exposure.     

Is Nai Habarala (Alocasia cucullata) a poisonous plant?

Repair of fetal diaphragmatic hernia has proven technically difficult especially when the left lobe of the fetal liver is incarcerated in the chest. A step-wise approach from both above and below the diaphragm solves several frustrating technical problems.     

Clear cell sarcoma (malignant melanoma of soft parts). Presentation of two additional cases

Clear cell sarcoma or malignant melanoma of soft parts is a rare tumor with a predilection for the extremities. Although characterized by a slow clinical course, prognosis is poor because of a high incidence of local recurrences and distant metastases. In this report, two additional cases which originated in the toes are presented.     

Factors affecting the ultrasonic properties of equine digital flexor tendons

Dietary treatment with three diets differing in vitamin E, Low E (15 mg of vitamin E/kg diet), Medium E (150 mg/kg), or High E (1,500 mg/kg), resulted in guinea pigs with low (but nondeficient), intermediate, or high heart alpha-tocopherol concentration. Neither the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and reductase, nor the nonenzymatic antioxidants, GSH, ascorbate, and uric acid were homeostatically depressed by increases in heart alpha-tocopherol. Protection from both enzymatic (NADPH dependent) and nonenzymatic (ascorbate-Fe2+) lipid peroxidation was strongly increased by vitamin E supplementation from Low to Medium E whereas no additional gain was obtained from the Medium E to the High E group. The GSH/GSSG and GSH/total glutathione ratios increased as a function of the vitamin E dietary concentration closely resembling the shape of the dependence of heart alpha-tocopherol on dietary vitamin E. The results show the capacity of dietary vitamin E to increase the global antioxidant capacity of the heart and to improve the heart redox status in both the lipid and water-soluble compartments. This capacity occurred at levels six times higher than the minimum daily requirement of vitamin E, even in the presence of optimum dietary vitamin C concentrations and basal unstressed conditions. The need for vitamin E dietary supplementation seems specially important in this tissue due to the low constitutive levels of endogenous enzymatic and nonenzymatic antioxidants present of the mammalian heart in comparison with those of other internal organs.