Inhibition of inducible nitric oxide synthase after myocardial ischemia increases coronary flow

BACKGROUND: The role of nitric oxide synthase in myocardial ischemia-reperfusion injury is complex. Our hypothesis was that inducible nitric oxide synthase has a role in the regulation of coronary flow after ischemia. METHODS: Four groups of isolated blood-perfused rabbit hearts underwent sequential periods of perfusion, ischemia, and reperfusion (20, 30, and 20 minutes). Two groups underwent 40 minutes of perfusion. Ischemic groups received saline vehicle, N omega-nitro-L-arginine methyl ester (L-NAME) or the highly specific inducible nitric oxide synthase inhibitor 1400W in low or high doses during reperfusion. Two nonischemic groups were treated with saline vehicle or 1400W during the last 20 minutes of perfusion. Left ventricular developed pressure and coronary flow were measured after each perfusion period. Ventricular levels of myeloperoxidase and cyclic guanosine monophosphate were measured at the end of the second perfusion period. RESULTS: Coronary flow was significantly increased in both 1400W groups versus L-NAME (p < 0.001) and in high-dose 1400W versus control (p < 0.001). Coronary flow was not significantly different between the nonischemic groups. Left ventricular developed pressure was not significantly different among the ischemic groups or between the two nonischemic groups. There were no differences in cyclic guanosine monophosphate levels in any of the ischemic hearts. Myeloperoxidase levels were significantly elevated in L-NAME versus high-dose 1400W, nonischemic 1400W, and nonischemic saline groups (p < 0.02). CONCLUSIONS: Highly selective inhibition of inducible nitric oxide synthase results in increased coronary flow after ischemia but not after continuous perfusion. This occurs with decreased neutrophil accumulation and a trend toward increased contractility without elevation of cyclic guanosine monophosphate levels.     

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs: a report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health

The relationship between characteristics of irritable bowel syndrome (IBS) and eating disorders (ED) was investigated in a clinical sample of 43 female and 17 male IBS patients who completed the Eating Disorder Inventory (EDI). A diagnosis of IBS was generally unrelated to the Body Dissatisfaction, Perfectionism, and Ineffectiveness subscales of the EDI, but symptom severity was correlated with Perfectionism and Ineffectiveness. Severe bouts of vomiting were significantly associated with desires for lower body weight and reported binge-purge behaviors and cognitions measured by the Bulimia subscale of the EDI. Results suggest the need for a more comprehensive understanding of both types of illness as well as a possible framework for future empirical work.     

Physicians'' attitudes toward patients'' use of alternative cancer therapies

Glucuronide conjugates of arylamines are thought to be important in the carcinogenic process. This study investigated the pH stability and synthesis of glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolites by human and dog liver. Both dog and human liver slices incubated with 0.06 mM [3H]-4-aminobiphenyl produced the N-glucuronide of 4-aminobiphenyl as the major product. After 2 hr of incubation, the N-glucuronide of 4-aminobiphenyl represented 52 and 27% of the total radioactivity recovered by HPLC in dog and human, respectively. When 4-aminobiphenyl, N-hydroxy-4-aminobiphenyl, or N-hydroxy-N-acetyl-4-aminobiphenyl was added to human microsomes containing [14C]UDP-glucuronic acid, a new product peak was detected by HPLC. At 0.5 mM, the rate of glucuronidation was N-hydroxy-N-acetyl-4-aminobiphenyl > N-hydroxy-4-aminobiphenyl > 4-aminobiphenyl. The rate of formation of the N-glucuronide of 4-aminobiphenyl was similar to that observed with benzidine and N-acetylbenzidine. The glucuronides of 4-aminobiphenyl and N-hydroxy-4-aminobiphenyl were both acid labile with T1/2 values of 10.5 and 32 min, respectively, at pH 5.5. The glucuronide of N-hydroxy-N-acetyl-4-aminobiphenyl was not acid labile with T1/2 values at pH 5.5 and 7.4 of 55 and 68 min, respectively. The glucuronide of 4-aminobiphenyl was the most acid labile conjugate examined. Thus, the glucuronide of 4-aminobiphenyl is a major product of dog and human liver slice metabolism and likely to play an important role in the carcinogenic process.     

Squamous cell carcinoma arising in thyroglossal duct remnant cyst epithelium

The extremely rare occurrence of invasive squamous cell carcinoma arising from normal epithelial lining of a thyroglossal duct remnant cyst is documented by demonstrating the histopathologic transition from normal squamous epithelium to squamous cell carcinoma. The requirements that must be fulfilled to accept a lesion as arising de novo from the epithelial lining are outlined, and all requirements are achieved. The lesion is differentiated from the less rare papillary or papillary-follicular adenocarcinoma of residual thyroid tissue of the thyroglossal duct tract remnants. This is the sixth report in the world literature of invasive squamous cell carcinoma arising from benign thyroglossal remnant squamous epithelium, and the second demonstrating the transition from normal squamous epithelium to invasive squamous cell carcinoma.     

Bioenergetics in clinical medicine. IX. Gingival and leucocytic deficiencies of coenzyme Q10 in patients with periodontal disease

The specific activities of the succinate dehydrogenase-coenzyme Q10 reductase in mitochondria were determined for patients from a normal periodontal practice. The criteria for selection were patients having a bone score of 1.0-4.0 and a pocket depth of 2.5-5.2 mm. All 29 patients showed a deficiency of 20-63% of CoQ10-enzyme activity in gingival biopsies. The mean value was elevated (P less than 0.001) over that of controls. For corresponding blood samples, 24/28 (86%) showed deficiencies of 20-66% and a higher (P less than 0.001) mean value than that of controls. Periodontal patients frequently have significant gingival and leucocytic deficiencies of CoQ10. The leucocytic deficiency indicates a systemic nutritional imbalance and is not likely caused by neglected oral hygiene. A gingival deficiency could predispose this tissue to periodontitis and this disease could even augment the deficiency. These results support previously suggested adjunctive use of CoQ10 with oral hygiene for improved treatment presumably through bioenergetics.