Approaches to vitamin B12 deficiency. Early treatment may prevent devastating complications

Vitamin B12 deficiency is a common problem that affects the general population and the elderly in particular. Persons with the deficiency may be asymptomatic or may have hematologic or neuropsychiatric signs and symptoms. If the disorder is untreated, complications may cause significant morbidity. In this article, Drs Dharmarajan and Norkus discuss approaches to screening and diagnosis as well as the nontoxic, low-cost treatments now available.     

Kidney stones,carbonic anhydrase inhibitors,and the ketogenic diet

PURPOSE: Because carbonic anhydrase inhibitors and the ketogenic diet are each known risk factors for kidney stones, simultaneous use of these therapies has been discouraged. The objective of this study was to establish the prevalence of nephrolithiasis in children in this combination-therapy population. METHODS: Since 1996, 301 children have been started on the ketogenic diet at our institution. A retrospective cohort study of renal calculi in ketogenic diet patients was performed to evaluate the increased risk with combined use of a carbonic anhydrase inhibitor. RESULTS: In 15 (6.7%) of 221 children on the ketogenic diet without the use of carbonic anhydrase inhibitors, stones developed. In five (6.3%) of the 80 children on the diet in combination with topiramate or zonisamide, stones developed. There was no difference between these two groups (p = 0.82). No child was treated with either acetazolamide or more than one carbonic anhydrase inhibitor simultaneously. Prior ketogenic diet duration was shorter (10.4 vs. 22.4 months; p = 0.03), and more children had either a family history of renal stones or significant urologic abnormalities (80 vs. 27%; p = 0.04) in the combination-therapy group. CONCLUSIONS: The combined use of carbonic anhydrase inhibitors and the ketogenic diet does not increase the risk of kidney stones. We recommend that all patients treated with combination therapy should be treated with increased hydration. Urine alkalinization should be considered for children with previous renal abnormalities, family histories of kidney stones, hematuria, or elevated urine calcium-to-creatinine ratios. If renal stones are found, we advocate discontinuation of the carbonic anhydrase inhibitor.     

Human microecology studies at Department of Microbiology with Virology and Immunology, I.M. Sechenov Moscow Medical Academy

Studies of human microflora in health and disease and during exposure to professional and ecological factors is a traditional problem solved for many years by staff members of Department of Microbiology with Virology and Immunology, I. M. Setchenov Moscow Medical Academy. The purpose of research is to develop methods and means for diagnosis and prevention of human microbiocenosis disorders. Fundamental and applied research in cooperation with prophylactic and clinical institutions and departments yielded data contributing to solution of many pressing problems in prevention and diagnosis of infectious diseases.     

Cooperation of the Russian Academy of Medical Sciences with the World Health Organization

The paper presents a brief review of successful cooperation of the Russian Academy of Medical Sciences (RAMS) with the World Health Organization (WHO) in developing biomedical research and promoting the scientific bases of public health. This cooperation is effected in different forms. The work of 30 WHO collaborating centers on the basis of 18 RAMS Research Institutions plays the leading part in this cooperation. The paper contains specific data on the activities of these centers in the field of medical research, scientific publications, education, and training of medical staff for Russia and other countries. The financial support given by the WHO to its collaborating centers is now very limited, but scientific information, medicaments, and equipment which can be received by the centers from this Organization are very valuable.     

Permeability barrier properties of oral keratinocyte cultures: a model of intact human oral mucosa

OBJECTIVES: The aim of this study was to establish whether an in vitro model of human oral mucosa had similar permeability characteristics to normal oral mucosa. Such a model would have considerable value as an alternative to the use of mucosal biopsies in studies of transmucosal drug delivery. MATERIALS AND METHODS: Keratinocytes obtained from buccal mucosa, hard palate and abdominal skin were seeded onto inert collagen membranes (Cellagen Discs) or dead de-epidermised dermis (DDED) and grown either as submerged or air-liquid interface cultures. Subsequently the ultrastructural characteristics, permeability to water and barrier lipid content of the epithelial cultures were assessed and compared with samples of intact mucosa and skin. RESULTS: All the cultures stratified into multilayered epithelia and displayed features of differentiation including tonofilaments, desmosomes and membrane coating granules. The permeability characteristics and barrier lipid content of the oral mucosal cultures resembled those of intact mucosa. By contrast, epidermal keratinocytes failed to produce a permeability barrier comparable with that of skin and had low levels of barrier associated lipids. CONCLUSIONS: Cultures of human oral mucosal keratinocytes obtained from healthy adults develop similar permeability properties and barrier lipid composition to their site of origin. This model system may be useful for the evaluation of local and systemic oral mucosal drug delivery.     

Development of an immunofluorometric assay and quantification of human kallikrein 7 in tissue extracts and biological fluids

BACKGROUND: Human kallikrein 7 (hK7), also known as human stratum corneum chymotryptic enzyme, is a chymotrypsin-like serine protease first identified in human skin extracts and predicted to be a secreted protease. The aim of this study was to develop a sensitive and specific immunoassay for hK7 and to examine the distribution of hK7 in tissue extracts and biological fluids. METHODS: Recombinant hK7 was produced in human embryonic kidney cells (HEK293T) and purified by a three-step column chromatographic procedure. The purified hK7 was injected into mice for antibody generation. A sandwich-type immunoassay was developed with the anti-hK7 monoclonal antibodies. RESULTS: The assay had imprecision (CV) <10% through the dynamic range of 0.2-20 microg/L and had no detectable cross-reactivity from other members in the human kallikrein gene family. Highest concentrations were found in skin, esophagus, and kidney. hK7 was also found in amniotic fluid, ascites from ovarian cancer patients, breast milk, cerebrospinal fluid, saliva, seminal plasma, serum, sweat, synovial fluid, and urine. CONCLUSIONS: This study describes the first ELISA-type immunoassay for hK7 protein quantification. hK7 is found many human tissues and in various biological fluids.