Normalization of enhanced hepatic gluconeogenesis by the antiglucocorticoid RU 38486 in acutely uraemic rats

Hepatic amino acid uptake, urea and glucose production are increased in acute uraemia. It has been shown that this metabolic pattern is mediated by glucocorticoids. Accordingly, the administration of the antiglucocorticoid RU 38486 to acutely uraemic rats resulted in a reduction of serum urea-N and glucose levels. To clarify whether this effect is due to a reduction in hepatic gluconeogenesis we examined the effect of the antiglucocorticoid RU 38486 on urea and glucose formation in isolated hepatocytes from sham-operated (SHAM) and bilaterally nephrectomized (BNX) rats receiving RU 38486 or the vehicle only. Hepatic glucose production in BNX rats was considerably increased from Na-pyruvate (+79%), alanine (+174%), glutamine (+158%), and serine (+87%) compared with SHAM animals. Concomitantly, hepatic urea formation was also enhanced from amino acid substrates in acutely uraemic rats. When uraemic animals were treated with RU 38486, glucose production from amino acids and Na-pyruvate was reduced to the range of SHAM animals or even lower. This effect could not be demonstrated in SHAM-operated controls. A comparable decrement in hepatic urea production was observed in BNX rats treated with the antiglucocorticoid. Thus, glucocorticoids appear to play a key role in the abnormal hepatic urea and glucose production of acutely uraemic rats.     

Nationwide survey of home transfusion practices

BACKGROUND: Limited information exists on home transfusion practices. STUDY DESIGN AND METHODS: In 1995, a survey requesting data for 1994 was sent to 1273 American Association of Blood Banks (AABB) institutional members and 113 non-AABB home health care agencies that provide out-of-hospital transfusions. RESULTS: Of 943 respondents, 102 provide blood to a home transfusion program, 37 provide blood and run a home transfusion program, and 13 run a home transfusion program only, for a total of 152 (16%) with some involvement in home blood transfusions. Most of the 50 respondents with a home transfusion program are licensed by their state and accredited by the Joint Commission on Accreditation of Healthcare Organizations. All respondents have written policies for home transfusion, and 90 percent require a signed informed-consent document before initiating transfusions in the home. Most have policies requiring that there be a second adult and a telephone in the home, that the home be deemed safe for transfusion, that the patient's physician be readily available, and that the patient have had prior transfusions. The most common component issued by the blood providers was red cells, followed by platelets. White cell-reduced components were always provided by 36 percent of respondents. The most common patient diagnosis was cancer. Home transfusions were provided primarily by registered nurses. Only 14 percent of respondents indicated that the medical director of the blood bank is responsible for approving a patient for home transfusion. A posttransfusion visit is performed by 46 percent of respondents. CONCLUSION: Although most facilities have policies for the administration of home transfusions, there remains marked heterogeneity among blood providers and transfusionists regarding home transfusion practices.     

Clinical perspectives on the role of the human papillomavirus vaccine in the prevention of cancer

The role of human papillomavirus (HPV) in the genesis of cervical cancer has been well documented, and an increasing body of literature exists with regard to the role of HPV in other cancers, including cancers of the head and neck. With the recent expansion of the United States Food and Drug Administration's approval of the quadrivalent HPV virus-like particle vaccine to include men and boys and approval of the bivalent vaccine this year, the controversies regarding who should be vaccinated, at what age is vaccination most appropriate, and the limitations of the available HPV vaccines are increasing. Health care providers are challenged with evaluating the current, but continually changing, clinical evidence when making critical decisions for their patients. A literature search of MEDLINE and SciVerse Scopus was conducted for articles published from 1998-April 2010 regarding HPV, HPV-related cancers, and HPV vaccines. Although both HPV vaccines were greater than 90% effective in the prevention of cervical cancer precursors in an according-to-protocol cohort, both vaccines were significantly less effective in the intent-to-treat population. In patients who achieved seroconversion, the geometric mean titers decrease dramatically within the first 2 years after vaccination, and then continue to decline at a slower rate. No effective antibody titer has been defined for either vaccine, and no studies have been conducted with documented HPV exposure after vaccination. With low efficacy rates in an intent-to-treat population and the potential for waning immunity, it is imperative for women to continue to receive regular Pap tests and gynecologic examinations. Although vaccine administration was shown to be cost-effective when administered to adolescent girls, many of these simulations overestimated the durability of protection, efficacy rates in sexually active women, impact of incomplete vaccination, or necessity of boosters in the future. Whereas the introduction of the HPV vaccine was an enormous advancement in the cancer prevention research arena, optimization of its clinical use is still needed.     

Hydrogen peroxide derived from amine oxidation mediates the interaction between aminosugars and semicarbazide-sensitive amine oxidase

Summary Semicarbazide-sensitive amine oxidase (SSAO) also functions as a vascular-adhesion protein (VAP-1). The nature of the target site on lymphocytes to which endothelial-cell SSAO/VAP-1 binds is unknown. We have shown that amino sugars (galactosamine, glucosamine and mannosamine), which are not SSAO substrates, can bind to the enzyme as reversible inhibitors. Thus, they serve as a model system in which to study the interaction process. Binding occurred during substrate (benzylamine) oxidation but not when the amino sugar was incubated, for extended periods, with SSAO alone. These results suggest that one, or more of the products of the SSAO-catalysed amine oxidation might be necessary for the inhibitory process to occur. Two of the reaction products of benzylamine oxidation, benzaldehyde and ammonia were found to have no effect on the inhibition of SSAO by galactosamine. Preincubation of the enzyme with galactosamine plus H₂O₂ was, however, found to result in time-dependent inhibition. This is not a result of the non-enzymic reaction between H₂O₂ and the amino sugar, since preincubation of galactosamine with H₂O₂ alone, for extended periods, did not give rise to an inhibitory species. The amount of exogenously added H₂O₂ necessary for inhibition was very much greater than that formed during substrate oxidation. These results suggest that the H₂O₂ formed as a product of the SSAO-catalysed oxidation reaction is more efective in promoting the binding of amino sugars.     

Olfaction in dentistry

Oral Diseases (2010) 16 , 221–232 Practitioners of oral medicine frequently encounter patients with complaints of taste disturbance. While some such complaints represent pathological processes specific to the gustatory system, per se, this is rarely the case. Unless taste‐bud mediated qualities such as sweet, sour, bitter, salty, umami, chalky, or metallic are involved, ‘taste’ dysfunction inevitably reflects damage to the sense of smell. Such ‘taste’ sensations as chicken, chocolate, coffee, raspberry, steak sauce, pizza, and hamburger are dependent upon stimulation of the olfactory receptors via the nasopharynx during deglutition. In this paper, we briefly review the anatomy, physiology, and pathophysiology of the olfactory system, along with means for clinically assessing its function. The prevalence, etiology, and nature of olfactory disorders commonly encountered in the dental clinic are addressed, along with approaches to therapy and patient management.