Tumor-specific immunotherapy of murine bladder cancer with butanol-extracted antigens and ethylchlorformate polymerized tumor protein

Successful treatment of superficial bladder cancer using nonspecific immunotherapy with Bacillus Calmette-Guerin (BCG) has been well documented. Investigation of two potential tumor-specific immunotherapeutic agents using a murine transitional-cell carcinoma model (MBT-2) is reported. The survival of mice immunized with tumor proteins obtained by treating tumor cells with either 1-butanol or ethylchlorformate was compared to the survival of animals immunized with BCG. Long-term immunity conferred by each of these agents was also assessed. Significant protection by both agents was noted in all treatment groups compared to controls. Long-term immunity was also found to result from treatment with both investigational agents as well as with BCG. Butanol-extracted antigens and ethylchlorformate polymerized tumor protein may be useful as immunotherapeutic alternatives to BCG.     

Fibroblast growth factor signaling in the developing neuroendocrine hypothalamus

Fibroblast growth factor (FGF) signaling is pivotal to the formation of numerous central regions. Increasing evidence suggests FGF signaling also directs the development of the neuroendocrine hypothalamus, a collection of neuroendocrine neurons originating primarily within the nose and the ventricular zone of the diencephalon. This review outlines evidence for a role of FGF signaling in the prenatal and postnatal development of several hypothalamic neuroendocrine systems. The emphasis is placed on the nasally derived gonadotropin-releasing hormone neurons, which depend on neurotrophic cues from FGF signaling throughout the neurons’ lifetime. Although less is known about neuroendocrine neurons derived from the diencephalon, recent studies suggest they also exhibit variable levels of dependence on FGF signaling. Overall, FGF signaling provides a broad spectrum of cues that ranges from genesis, cell survival/death, migration, morphological changes, to hormone synthesis in the neuroendocrine hypothalamus. Abnormal FGF signaling will deleteriously impact multiple hypothalamic neuroendocrine systems, resulting in the disruption of diverse physiological functions.     

Warfarin toxicity and individual variability-clinical case

Warfarin is a widely used anticoagulant in the treatment and prevention of thrombosis, in the treatment for chronic atrial fibrillation, mechanical valves, pulmonary embolism, and dilated cardiomyopathy. It is tasteless and colorless, was used as a poison, and is still marketed as a pesticide against rats and mice. Several long-acting warfarin derivatives-superwarfarin anticoagulants-such as brodifacoum, diphenadione, chlorophacinone, bromadiolone, are used as pesticides and can produce profound and prolonged anticoagulation. Several factors increase the risk of warfarin toxicity. However, polymorphisms in cytochrome P450 genes and drug interactions account for most of the risk for toxicity complications. Each person is unique in their degree of susceptibility to toxic agents. The toxicity interpretation and the health risk of most toxic substances are a subject of uncertainty. Genetically determined low metabolic capacity in an individual can dramatically alter the toxin and metabolite levels from those normally expected, which is crucial for drugs with a narrow therapeutic index, like warfarin. Personalized approaches in interpretation have the potential to remove some of the scientific uncertainties in toxicity cases.     

Post-hatch oral estrogen in zebra finches (Taeniopygia guttata): Is infertility due to disrupted testes morphology or reduced copulatory behavior?

Previous studies show that post-hatch oral exposure of zebra finches to estradiol benzoate compromises male fertility, but the basis of the infertility is not clear. In this study, zebra finch nestlings were orally dosed with estradiol benzoate (at 1, 10, or 100 nmol/g BW per day, post-hatch days 5 to 11 [EB1, EB10, and EB100, respectively]). EB10 and EB100 males exhibited no significant differences in the frequency of mounting behavior (compared to canola oil [vehicle]-treated controls), when observed for six weeks as adults in communal breeding cages with similarly treated females; EB1 males showed reduced mounting behavior compared to controls (p < 0.05). EB- and control-treated adult pairs were subsequently co-housed in a communal breeding trial to determine the extent of parentage outside the established pair-bond. Microsatellite analysis was consistent with EB-treated males having lower success than controls in obtaining paternity outside the established pair-bond. Histological examination of testes revealed dose-related disruption of normal morphology: disrupted basal-to-lumen laminarity of spermatogenesis stages, increased vacuolization within seminiferous tubules, decreased sperm aggregation and decreased spermatid density. Additionally, EB100 and control males were housed individually, implanted with testosterone propionate (TP) and presented with a female 3, 5, 9, and 11 days post-implantation for assessment of male sexual behavior. EB-treated, TP-implanted birds showed a slight decrease in mounting and singing behavior on day 5 after implantation; other male courtship behaviors (display, solicitation) were unaffected. Taken together, these results suggest that infertility in male zebra finches resulting from early oral estrogen exposure is more likely due to disrupted testicular morphology than altered sexual behavior.     

Targeting the COPD exacerbation

Exacerbations of COPD have a profound detrimental effect on the patient and impose a significant burden on healthcare resource utilization. Prevention and treatment of exacerbations are major objectives of the clinical management of COPD. For this approach to be successful, clinicians must combine both pharmacologic approaches and non-pharmacologic strategies aimed at improving the patient's disease management. Non-pharmacologic approaches include those that can be incorporated into the office setting as well as intervention strategies that are integrated into the lifelong management of COPD. These strategies include developing a partnership with the patient and their social supports, encouraging and facilitating smoking cessation, immunizations, proper use of supplemental oxygen, and most importantly, giving the patient the tools to manage their illness appropriately. Moreover there is clear evidence of an irrevocable decline in pulmonary function after each exacerbation, usually resulting in reduced physical activity and impaired skeletal muscle function. Not surprisingly, pulmonary rehabilitation after such events has been shown to prevent relapse, improve survival and enhance patients' overall function after acute exacerbations.