Differential host susceptibility to pulmonary infections with bacteria and fungi in mice deficient in myeloperoxidase

Myeloperoxidase (MPO), which is located within neutrophils capable of producing hypochlorous acid, is active in vitro against bacteria and fungi. However, MPO-deficient persons are usually healthy. To define the in vivo contribution of MPO to early host defense against pulmonary infections, MPO-deficient and control mice were intranasally infected with various fungi and bacteria, and the number of residual microorganisms in lungs was compared 48 h later. MPO-deficient mice showed severely reduced cytotoxicity to Candida albicans, Candida tropicalis, Trichosporon asahii, and Pseudomonas aeruginosa. However, the mutant mice showed a slight but significantly delayed clearance of Aspergillus fumigatus and Klebsiella pneumoniae and had comparable levels of resistance to the wild type against Candida glabrata, Cryptococcus neoformans, Staphylococcus aureus, and Streptococcus pneumoniae. These results suggest that the MPO-dependent oxidative system is important for host defense against fungi and bacteria, although the effect varies by pathogen species.     

Molecular genetic approaches to Mycobacterium tuberculosis

Recent progress of molecular genetics has been providing tools for new approaches to disease treatment and diagnosis of Mycobacterium tuberculosis. In 1998, Cole et al. reported the complete genome sequence of Mycobacterium tuberculosis. The new information will provide us the knowledge and understanding of the biology of Mycobacterium tuberculosis. Further, it will provide us new conception of diagnosis and treatment of the disease. Four topics were selected in this symposium. Dr. Iinuma reviewed and prospected the clinical utility of nucleic acid amplification methods of Mycobacterium tuberculosis. Dr. Suzuki reviewed the molecular mechanism of acquired resistance to anti-TB drugs and reported the early detection of genetic mutation by new designed DNA tip method. Dr. Takahashi reviewed the method of molecular epidemiology and genetic elements as a tool for strain differentiation of tuberculosis. Dr. Mizuguchi interpreted the essential feature of mycobacterial genome maps, and genes and their biological activity. He also reviewed the importance and the utility of the complete genome sequence of tuberculosis in association with pathogenecity. These topics were summarized in this report, based on the symposium of "Molecular genetic approaches to Mycobacterium tuberculosis" in the 75th annual meeting of the Japanese Society for Tuberculosis.     

Prognostic significance of time-delay to peak creatine kinase after direct percutaneous coronary intervention in acute myocardial infarction patients

The aim of the present study was to investigate the prognostic significance of time-delay to peak creatine kinase (CK) after successful direct percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Our 240 consecutive first AMI attack subjects admitted within 5 hours from onset were successfully reperfused by direct PCI therapy. Subjects were divided into two groups according to the upper quartile value of peak-CK time from onset, the early peak-CK group (peak-CK time < or = 16 hours from onset, n = 180) and the late peak-CK group (peak-CK time > 16 hours, n = 60). (I) The early ST-segment resolution rate was lower in the late peak-CK group compared with the early peak-CK group (P < 0.05), and there were significantly fewer patients with preinfarction angina pectoris in the late peak-CK group than in the early peak-CK group (P < 0.01). (II) LVEF in the chronic stage was significantly lower in the late peak-CK group than in the early peak-CK group (49 +/- 13% versus 57 +/- 13%, P < 0.001). (III) There were significantly more patients with major complications in the late peak-CK group than in the early peak-CK group (required CABG: 10% versus 3%, P < 0.05; cardiac death: 18% versus 3%, P = 0.0001). (IV) Multivariate analysis identified late peak-CK as an independent predictor of cardiac death (Odds ratio 7.91, 95% C.I. 1.40-44.11, P < 0.05). In patients with AMI, the time-delay to peak-CK after successful direct PCI may be closely related to left-ventricular systolic dysfunction and poor patient outcome, including mortality.     

Clinical effects of nitrendipine on variant angina pectoris

The clinical effects of nitrendipine, a new calcium antagonist, were investigated in a single-blind test on 21 patients with variant angina pectoris. The efficacy of the drug was evaluated on the basis of frequency of anginal attacks and Holter electrocardiographic findings during different treatment periods at doses of 10 mg once a day (period I) and 20 mg once a day (period II). The number of anginal attacks decreased significantly from a pretreatment level of 2.1 +/- 0.3 per day to 0.7 +/- 0.2 per day in treatment period I and 0.3 +/- 0.1 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The consumption of sublingual nitroglycerin tablets decreased significantly in both treatment periods in comparison with the observation period before treatment (p less than 0.01, p less than 0.001, respectively). In 20 patients with continuous ECG monitoring, the frequency of ST-segment elevation was 4.5 +/- 1.0 per day during the pretreatment period; it decreased significantly to 0.9 +/- 0.6 per day in treatment period I and 0.5 +/- 0.3 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The duration and the maximum magnitude of ST-segment elevation also improved significantly in both treatment periods. These results demonstrate the efficacy of nitrendipine in the treatment of variant angina at a single daily dose of 10 mg.     

Treatment with argon plasma coagulation reduces recurrence after piecemeal resection of large sessile colonic polyps: a randomized trial and recommendations

BACKGROUND: Recurrence is frequent after piecemeal snare resection of large sessile colorectal polyps. The aim of this study was to evaluate the safety and efficacy of argon plasma coagulation (APC) in preventing recurrence when applied to the edge and base of the polypectomy site after apparently complete piecemeal resection. METHODS: Patients with large (>1.5 cm) sessile polyps removed by piecemeal snare cautery were placed into 2 groups. The first consisted of patients with polyps believed by the endoscopist to be completely excised. These patients were randomized to either no further therapy (control) or to APC of the rim and any residual mucosal or submucosal tissue in the base of the polypectomy site. The second group comprised patients in whom polyps, as judged by the endoscopist, were incompletely excised by snare polypectomy; APC was routinely applied without randomization to all visible remaining adenomatous tissue. Follow-up colonoscopy was performed within 3 months and 1 year; biopsy specimens were taken routinely from the resection site and further polypectomy was performed as indicated. RESULTS: There were fewer recurrences after APC in the randomized group (1/10 APC, 7/11 no APC; p = 0.02). In the group with initial incomplete snare polypectomy, recurrence was detected at 3 months in 6 of 13 despite APC. One patient was hospitalized with abdominal pain and minor rectal bleeding but required no intervention. There were no other episodes of significant late bleeding caused by piecemeal polypectomy. One patient was referred for surgery after unsuccessful endoscopic management. CONCLUSIONS: In patients with apparent complete endoscopic snare resection of large adenomas, postpolypectomy application of APC reduces adenomatous recurrence.     

Influence of inhaled corticosteroids on community-acquired pneumonia in patients with bronchial asthma

OBJECTIVE: The aim of the present study was to evaluate the influence of inhaled corticosteroids (ICS) on community-acquired pneumonia (CAP) in patients with asthma. PATIENTS AND METHODS: All asthmatic patients who required hospitalization for CAP from the beginning of 1989 through December 2001 were enrolled in this retrospective study. Patients who used oral corticosteroids daily were excluded. Patients were divided into two groups based on whether or not they used ICS, and we analyzed clinical characteristics of the pneumonia. Sixty-two patients (28 males, 34 females; mean age, 54.5 years) were enrolled in this study. Thirty-seven of 62 patients used ICS, with the mean dosage being 777.9 microg/day. RESULTS: We found no significant differences between the two groups with regard to mean age, serum albumin level, duration of asthma, pulmonary function and frequency of intravenous infusion of corticosteroids in the outpatient department. There were no significant differences in body temperature, white blood cell count, and CRP value upon admission between the two groups. Differences were not significant in the period of resolution of the pneumonia or in the frequency of pathogens identified between the two groups. CONCLUSION: ICS therapy appears to have no influence on CAP in patients with asthma. We recommend that ICS should be continued to control asthma with adequate antibiotic therapy when asthmatic patients have CAP.     

Small dense LDL phenotype is associated with postprandial increases of large VLDL and remnant-like particles in patients with acute myocardial infarction

BACKGROUND: The small dense low-density lipoprotein (LDL) phenotype (pattern B), high concentrations of remnant-like particles (RLPs), and postprandial lipemia are newly recognized risk factors for coronary heart disease (CHD). However, the associations of these lipoprotein abnormalities remain unclear. The aim of this study was to investigate the relationships among LDL phenotype, very-low-density lipoprotein (VLDL) subclasses, and postprandial lipoprotein metabolism in CHD patients. METHOD: We performed an oral fat tolerance test in 32 patients with acute myocardial infarction and compared the following parameters between patients characterized by either large buoyant LDL (pattern A) versus pattern B: lipids and apolipoproteins (apo) in the plasma and Svedberg flotation rates (Sf) >400 (chylomicron), Sf 60-400 (large VLDL), and Sf 20-60 (small VLDL) fractions. RESULT: Fasting levels of triglyceride, RLP-cholesterol and RLP-triglyceride were slightly higher in the pattern B patients. Postprandial increases of RLP-cholesterol and the cholesterol and triglyceride of large VLDL fractions were significantly greater in the pattern B patients. The areas under the curves of cholesterol, triglyceride, and apo-B in large VLDL fractions were significantly higher in pattern B, while those in small VLDL were not. RLP-cholesterol and RLP-triglyceride in fasting and fed states correlated very highly with the corresponding cholesterol and triglyceride concentrations in large VLDL fractions. CONCLUSION: These results suggest that postprandial increase of large VLDL fractions and RLPs contribute to the formation of small dense LDL in CHD patients.     

Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor α production in trinitrobenzene sulphonic acid induced colitis

Background—It is well established that glutaminesupplemented elemental diets result in less severe intestinal damage inexperimental colitis. However, few studies have examined the mode ofaction of glutamine in reducing intestinal damage.
Aims—To examine the effects of glutaminesupplemented elemental diets on the potent inflammatory cytokinesinterleukin 8 (IL-8) and tumour necrosis factor α (TNF-α) intrinitrobenzene sulphonic acid (TNBS) induced colitis which presentswith both acute and chronic features of ulcerative colitis.
Methods—Sprague-Dawley rats were randomised intothree dietary groups and fed 20% casein (controls), or 20% caseinsupplemented with either 2% glutamine (2% Gln) or 4% glutamine (4%Gln). After two weeks they received intracolonic TNBS to inducecolitis.
Results—Both Gln groups of rats gained more weight thanthe control group (p<0.05) which had progressive weight loss. Colon weight, macroscopic, and microscopic damage scores for the Gln groupswere lower than in the control group (p<0.05). IL-8 and TNF-αconcentrations in inflamed colonic tissues were lower in the Gln groupsthan in the control group (p<0.05), and correlated well with diseaseseverity. Bacterial translocation was lower both in incidence (p<0.05)and in the number of colony forming units (p<0.05) for the Gln groups,than in the control group. With respect to all indices studied, the 4%Gln group performed better than did the 2% Gln group.
Conclusion—Prophylactic glutamine supplementationmodulates the inflammatory activities of IL-8 and TNF-α in TNBSinduced colitis.

Keywords:glutamine; trinitrobenzene sulphonic acid; inflammatory bowel disease; rats; interleukin 8; tumour necrosis factorα

     

Paradoxical effect of perchlorate on thyroidal weight, glucose 6-phosphate dehydrogenase and polyamines in methylthiouracil-treated rats

The effect of sodium perchlorate (NaClO4) on the methylthiouracil-induced increase in the activity of thyroid glucose 6-phosphate dehydrogenase (G6PDH), ornithine decarboxylase (ODC) and polyamine contents was studied in the rat. The G6PDH activity was increased nearly three-fold by methylthiouracil (MTU) but not by ClO4- at 7 days of treatment. Perchlorate lowered the MTU-induced enzyme activity to nearly the control level, without changing circulating thyrotrophin (TSH). The anion had no inhibitory effect on G6PDH activity in vitro. The possibility that an inhibitor specific for G6PDH was generated in ClO4- - treated rat thyroids was excluded. The activity of ODC was greatly increased by both ClO4- and MTU, the increase being significant as early as on the second day of treatment. Perchlorate had no inhibitory effect on MTU-induced ODC activity in vivo but decreased total contents of spermidine and spermine in the thyroid, without affecting the concentration (nmoles/g wet weight) of the polyamines. These results suggest that ClO4- acts directly on the thyroid to suppress specifically the stimulatory effect of TSH on G6PDH activity and possibly on polyamine accumulation.