Different starting times of alpha-tocopherol and gamma-tocotrienol supplementation and tumor marker enzyme activities in the rat chemically induced with cancer

1. alpha-Tocopherol (alpha-T) and gamma-tocotrienol (gamma-T) were supplemented continuously for 8 weeks in the diets of normal rats and rats chemically induced with cancer using diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF) and partial hepatectomy. Hepatocarcinogenesis was followed by determining the plasma gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase (ALP) activities as well as placental glutathione S-transferase (PGST) and GGT activities histochemically, at 4-week intervals. 2. Male Rattus norvegicus were supplemented alpha-T and gamma-T at two different doses of 30 and 300 mg/kg diet. The supplementation was started at three different times: simultaneously with DEN administration; 4 weeks; and 8 weeks after DEN administration. 3. Elevation of plasma GGT activities and formation of PGST and GGT positive foci were attenuated significantly (P < 0.05) when alpha-T and gamma-T were supplemented simultaneously with cancer induction. Supplementation begun 4 and 8 weeks after cancer induction did not affect plasma enzyme activities and formation of enzyme-positive foci. 4. alpha-T was more effective than gamma-T, and a lower dose of 30 mg/kg was found to be more effective in reducing the severity of hepatocarcinogenesis.     

Validity of screening for individuals at risk for type I diabetes by combined analysis of antibodies to recombinant proteins

OBJECTIVE: To determine whether screening for the presence of multiple antibody markers for IDDM is effective at identifying individuals with high risk for disease development. RESEARCH DESIGN AND METHODS: Antibodies to GAD and the tyrosine phosphatase-like protein 1A-2 were determined in sequential serum samples from 44 first-degree relatives of IDDM patients, identified as possessing islet cell antibody (ICA) and/or insulin autoantibody (IAA), who were followed prospectively for IDDM development, ICA, IAA, and antibodies to GAD and 1A-2 were also determined in 93 cases of new-onset nonfamilial IDDM. RESULTS: The presence of two or more antibodies in addition to ICA or IAA conferred high risk (61%) for development of IDDM within 5 years of entry into the study and identified 89% of those who have developed IDDM on current follow-up. None of the relatives positive for ICA or IAA alone, in the absence of other antibody markers, have developed IDDM. Antibodies to islet antigens could both appear and disappear in follow-up samples obtained after entry into the study. The majority (60%) of young (< 16 years), sporadic cases of IDDM had multiple antibodies to islet antigens, but this proportion was lower in older patients (37%). CONCLUSIONS: A screening strategy based on the analysis of antibodies to multiple islet antigens can predict IDDM at high sensitivity and specificity in families, and such a strategy may also be applicable to identify young individuals in the general population with high disease risk. Since appearance of antibodies to different antigens occurs sequentially rather than simultaneously, accurate assessment of diabetes risk based on the presence of multiple antibodies will require follow-up over a number of years after the first evidence of islet autoimmunity.     

Spectroscopy of NbO: Characterization of the Doublet Manifold

Disorder in sister chromatid separation can lead to genome instability and cancer. A temperature-sensitive S. pombe mis6-302 frequently loses a minichromosome at 26 degrees C and abolishes equal segregation of regular chromosomes at 36 degrees C. The mis6+ gene is essential for viability, and its deletion results in missegregation identical to mis6-302. Mis6 acts before or at the onset of S phase, and mitotic missegregation defects are produced only after the passage of G1/S at 36 degrees C. Mis6 locates at the centromeres throughout the cell cycle. In the mutant, positioning of the centromeres becomes abnormal, and specialized chromatin in the inner centromeres, which give the smear micrococcal nuclease pattern in wild type, is disrupted. The ability to establish correct biorientation of sister centromeres in metaphase cells requires the Mis6-containing chromatin and originates during the passage of G1/S.     

Diagnosing anal sphincter injury with transanal ultrasound and manometry

PURPOSE: This study was undertaken to evaluate how well anorectal manometry and transanal ultrasonography diagnose anal sphincter injury. METHODS: Anorectal manometry and transanal ultrasonography were performed in 20 asymptomatic nulliparous women and 20 asymptomatic parous women, and the results were compared with those obtained in 31 incontinent women who subsequently underwent sphincteroplasty and, thus, had operatively verified anal sphincter injury. By using computerized manometry analysis, mean maximum resting and squeeze pressures, sphincter length, and vector symmetry were determined in all women. All transanal ultrasounds were interpreted blinded as to the patient's history, physical examination, and manometry results. RESULTS: Manometric resting and squeeze pressures were significantly higher in the asymptomatic nulliparous women than in the asymptomatic parous women, and both groups had significantly higher pressures than the incontinent women (P < 0.001). Anal sphincter length and vector symmetry index were significantly decreased in incontinent women compared with asymptomatic women (P < 0.01). Decreased resting and squeeze pressures suggestive of possible sphincter injury were found in 90 percent of incontinent women with known anal sphincter injury. Decreased anal sphincter length and vector symmetry were found in only 42 percent of women with known anal sphincter injury. Transanal ultrasound was able to identify 100 percent of the known sphincter injuries but also falsely diagnosed injury in 10 percent of the asymptomatic nulliparous women with intact anal sphincters. False identification of sphincter injury increased when transanal ultrasound scanning was performed proximal to the distal 1.5 cm of the anal canal. CONCLUSION: Although nonspecific, decreased resting and squeeze pressures were found in 90 percent of patients with anal sphincter injury. Decreased anal sphincter length or vector symmetry index were present in only 42 percent of patients with known sphincter injury. When limited to the distal 1.5 cm of the anal canal, transanal ultrasound identified all known sphincter injuries but falsely identified injury in 10 percent of women with intact anal sphincters. Transanal ultrasound in combination with decreased anal pressures correctly identified all intact sphincters and 90 percent of known anal sphincter injuries.     

Overdose among youth in Bahrain: psycho-social characteristics, contact with helping agencies and problems

The in vitro minimal inhibitory concentrations (MIC) and minimal bactericidal concentration (MBC) of roxithromycin and erythromycin against Actinobacillus actinomycetemcomitans were evaluated. Sixty-seven different A. actinomycetemcomitans isolated from periodontal pockets of 101 subjects with different forms of early-onset and adult periodontitis and three reference strains of A. actinomycetemcomitans (ATCC 29522, ATCC 29523, and NCTC 9710) were included in this study. Erythromycin showed poor in vitro activity against A. actinomycetemcomitans; roxithromycin, on the contrary, exhibited good in vitro activity. Moreover, roxithromycin showed the best in vitro antimicrobial activity against 17 serotype a and 12 serotype c subpopulations of A. actinomycetemcomitans; against 38 serotype b subpopulation of A. actinomycetemcomitans, roxithromycin was consistently active. Roxithromycin exhibited MBC values usually equal to, or one-fold higher than MIC values. All the MBC values of erythromycin were three- to four-fold higher than the respective MIC result. Since roxithromycin is characterized by high concentrations in serum and good penetration and diffusion into gingival tissue, it could be expected to pass into the gingival crevicular fluid at levels sufficiently high to inhibit A. actinomycetemcomitans in vivo. These data indicate that roxithromycin might be a potential candidate for therapeutic trials in patients with A. actinomycetemcomitans-associated periodontitis.     

Design and synthesis of amphipathic antimicrobial peptides

A large proportion of antimicrobial peptides share a common structural feature that is critical to their antimicrobial activity, i.e. amphipathic alpha-helices. The amphipathy of a polypeptide chain can be quantitated through the value of the hydrophobic moment. Generally, antimicrobial peptides are characterized by high hydrophobic moment and low hydrophobicity values. Using these criteria we have identified two short segments that possess hydrophobic moment properties associated with known antimicrobial peptides. Using in vitro assays the segment derived from the protein perforin displays no antifungal or antibacterial activity and, while showing no alpha-helicity in buffer or liposomes, exhibits a modest degree of alpha-helical structure in the presence of the alpha-helical inducer, 2,2,2-trifluoroethanol. However, rational modifications result in a derivative which assumes an alpha-helical conformation in the presence of liposomes, exhibits potent antifungal activity against plant fungal pathogens, has significant antibacterial activity, effects leakage of a fluorescent dye from acidic liposomes and is devoid of hemolytic activity. Results are also presented for a segment derived from the human immunodeficiency virus envelope protein. We suggest that the identification of putative amphipathic structures in proteins may provide a useful starting strategy in the design and synthesis of antimicrobial peptides.