Increased oxidative stress in children exposed to passive smoking

BACKGROUND: Atherogenic process is accelerated with cigarette smoke that contains many oxidants and prooxidants, capable of producing free radical and enhancing the oxidative stress. We investigated oxidative and antioxidative status of children who had been exposed to passive smoking and compared with those of not exposed group. METHODS: One hundred forty-three school children aged 9-13 years, 61 of whom had never been exposed to passive smoking, and 82 of whom had been exposed to passive smoking at least 10 cigarette per day for at least last 1 year in their house, were enrolled in this study. Total antioxidative response (TAR) was measured to determine antioxidative status of plasma, and total peroxide concentration was measured to determine oxidative status of plasma. The ratio of TAR to total peroxide was accepted as an indicator of oxidative stress. RESULTS: TAR of plasma was significantly lower in children exposed to passive smoking than in those of not exposed group (p=0.018). Mean (S.D.) values were 1.49 (0.07) and 1.52 (0.08) mmol Trolox Equiv./l, respectively. In contrary, the mean (S.D.) total peroxide level of plasma was significantly higher in children exposed to passive smoking [13.06 (2.34) micromol H2O2/l] than in not exposed group [12.24 (1.74) micromol H2O2/l] (p=0.015). The mean (S.D.) oxidative stress index (OSI) value was significantly higher in the children exposed to passive smoking [0.87 (0.15)] than in not exposed group [0.80 (0.10)] (p=0.001). CONCLUSION: Children who are exposed to passive smoking are exposed to oxidative stress, which has been implicated in the etiopathogenesis of over 100 disorders including atherosclerosis.     

Evaluation of the clinical usefulness of mycobacterial skin test antigens in adults with pulmonary mycobacterioses.

A double-blind, multicenter study was conducted to evaluate the usefulness of mycobacterial skin test antigens for the specific diagnosis of adult pulmonary mycobacterial disease. The skin test antigens used were PPD-T (M. bovis) and PPD-B (M. intracellulare), made bioequivalent to 5 TU PPD-S through bioassay in human subjects. Of the 192 adults (18 yr of age or older), those with disease caused by M. tuberculosis (MTB) had significantly larger reactions to PPD-T than did those with disease caused by nontuberculous mycobacteria (NTM) or those with negative culture results (NEG)(13.41 mm versus 4.87 and 4.96 mm, respectively, p less than 0.001). The mean induration to PPD-B in NTM was not different from that in MTB or NEG. Defining a "positive" to be greater than or equal to 10 mm induration and a size difference of greater than or equal to 3 mm between PPD-T and PPD-B, the sensitivity, specificity, and positive predictive value (PPV) for PPD-T in diagnosing MTB versus NTM was 29, 90, and 75%. Corresponding values for PPD-B and NTM disease were 70, 61, and 64%. Dual testing was less useful in distinguishing disease caused by any of the mycobacteria from NEG. Although the sensitivity of PPD-B, made bioequivalent to PPD-S, was high, the specificity and PPV were low. We conclude that this preparation of PPD-B is no more useful in distinguishing adult pulmonary disease caused by NTM than is PPD-T alone.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Nonsteroidal anti-inflammatory drug sensitizes Mycobacterium tuberculosis to endogenous and exogenous antimicrobials

Existing drugs are slow to eradicate Mycobacterium tuberculosis (Mtb) in patients and have failed to control tuberculosis globally. One reason may be that host conditions impair Mtb’s replication, reducing its sensitivity to most antiinfectives. We devised a high-throughput screen for compounds that kill Mtb when its replication has been halted by reactive nitrogen intermediates (RNIs), acid, hypoxia, and a fatty acid carbon source. At concentrations routinely achieved in human blood, oxyphenbutazone (OPB), an inexpensive anti-inflammatory drug, was selectively mycobactericidal to nonreplicating (NR) Mtb. Its cidal activity depended on mild acid and was augmented by RNIs and fatty acid. Acid and RNIs fostered OPB’s 4-hydroxylation. The resultant 4-butyl-4-hydroxy-1-(4-hydroxyphenyl)-2-phenylpyrazolidine-3,5-dione (4-OH-OPB) killed both replicating and NR Mtb, including Mtb resistant to standard drugs. 4-OH-OPB depleted flavins and formed covalent adducts with N-acetyl-cysteine and mycothiol. 4-OH-OPB killed Mtb synergistically with oxidants and several antituberculosis drugs. Thus, conditions that block Mtb’s replication modify OPB and enhance its cidal action. Modified OPB kills both replicating and NR Mtb and sensitizes both to host-derived and medicinal antimycobacterial agents.Some bacterial infections can be cured with a single dose of an antibiotic, and most others can be cured with administration of one drug over several days or weeks. In contrast, routine treatment of drug-sensitive tuberculosis (TB) takes 2 mo of therapy with four drugs and an additional 4 mo with two drugs to reduce the 2-y relapse rate below 5%. The difficulty of completing prolonged treatment is a major reason for emergence of drug resistance. When the infecting strain is resistant to isoniazid and rifampin, the two drugs recommended for all 6 mo of treatment, cure often requires 2 y of daily administration of toxic, expensive, second-line agents that are often unavailable at the point of care. When the causative strain is additionally resistant to a quinolone and an aminoglycoside, the resultant “extensively drug-resistant” TB was fatal to 80% of patients in a leading center (1), although complex multidrug regimens have achieved higher cure rates in populations not previously exposed to the additional drugs (2). In addition to sharing air with someone with TB, leading risk factors for contracting the disease are malnutrition, HIV infection, diabetes, and exposure to smoke from cigarettes or cooking fires (3). These epidemiological challenges exacerbate problems of inadequate diagnostic technology and limited access to drug susceptibility testing and to drugs. Control of the pandemic is not in sight (3).It is widely hypothesized that treatment of TB is protracted because nonreplicating (NR) subpopulations of bacilli are phenotypically tolerant to drugs that were selected for activity against replicating (R) Mycobacterium tuberculosis (Mtb) (4). Mtb can occupy diverse microenvironments in the host. Evidence from auxotrophs, analyses of gene expression, and direct and indirect biochemical measurements in vivo or ex vivo in experimental animals and people suggest that such environments expose Mtb to acid, hypoxia, reactive nitrogen intermediates (RNIs), oxidative stress, carbohydrate deficiency, and metal starvation or intoxication, and require Mtb to metabolize fatty acids or cholesterol (5–17). In vitro, many of the same conditions can make Mtb relatively refractory to killing by the standard agents, except for pyrazinamide, which is only effective at a low pH.Thus, there is a need for a high-throughput screen (HTS) for compounds that kill Mtb when the Mtb has been rendered NR by a combination of physiologically relevant host-imposed conditions. We were encouraged to devise such a screen by recent discoveries of a class of compounds that kill Mtb only when it is NR (18), an antibiotic in clinical use for other infections that kills NR Mtb better than R Mtb (19), and a compound that kills NR and R Mtb equally well (20). Unfortunately, only one of those compounds is an approved drug, and even if it were of proven utility in TB, its price would preclude its use by most of those who need it. We decided to screen other existing drugs that are not regarded as antiinfectives for those that kill NR Mtb. Here, we report finding such a drug in an HTS that combined four host-imposed conditions, some of which converted the drug into a form active on both R and NR Mtb.     

Risk factors for avascular bone necrosis in patients with systemic lupus erythematosus

The objective was to investigate the predictive factors for avascular necrosis (AVN) of bone in patients with systemic lupus erythematosus (SLE). The records of 868 patients with SLE from four centers were reviewed retrospectively. Forty-nine patients with AVN were identified. A total of 154 patients with SLE who did not have clinically apparent AVN during the follow-up were evaluated as a control group. The demographic, clinical, laboratory and management characteristics of these two groups of patients were recorded according to predefined protocol and compared. The prevalence of AVN was detected 6% in our SLE population. The highest dose corticosteroid administered within 4?months and total cumulative prednisolone dose were significantly higher in the SLE patients with AVN. The use of cytotoxic agent significantly higher proportion of patients with AVN. AVN tends to develop more frequently in male gender and younger patients. Oral ulcer, pleuritis, Raynaud??s phenomenon, cutaneous vasculitis, lymphadenopathy, autoimmune thyroiditis, peripheral neuropathy and Sj?gren??s syndrome were higher incidence in SLE patients with AVN. The bilateral femoral heads were the commonest site of involvement of AVN in our patients with SLE.     

Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons

The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1-7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Phe- amide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels (at 120 minutes of exposure) and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.     

Neuromuscular transmission in hypoxemic patients with chronic obstructive pulmonary disease

Many studies have focused on the systemic effects of chronic obstructive pulmonary disease (COPD), but none has examined neuromuscular junction transmission (NMT). We evaluated NMT dysfunction using single-fiber electromyography (SFEMG) in patients with COPD. Twenty patients with COPD and 20 age-matched healthy controls were included in the study. All patients and controls underwent SFEMG. Abnormal NMT was found in seven of 20 patients (35%), but in none of the control subjects. The COPD patients were subgrouped according to the presence of hypoxemia. The patients with normoxemia were classified as Group 1, and the patients with hypoxemia were classified as Group 2. Abnormal NMT was found in six patients in Group 2 and in one in Group 1. While there was significant difference in terms of abnormal NMT between Group 2 and the controls, there was none between Group 1 and the controls. Our results show that NMT abnormalities can be present in hypoxemic patients with COPD.     

Effects of different bleaching methods on shear bond strengths of orthodontic brackets

Objective:To evaluate the effects of different bleaching methods on the shear bond strength (SBS) of orthodontic brackets.Materials and Methods:Forty-five freshly extracted premolars were randomly divided into three groups (n  =  15 per group). In group I, bleaching was performed with the office bleaching method. In group II, bleaching was performed with the home bleaching method. Group III served as the control. Orthodontic brackets were bonded with a light cure composite resin and cured with an LED light. After bonding, the SBS of the brackets were tested with a Universal testing machine.Results:Analysis of variance indicated a significant difference between groups (P < .001). The highest values for SBS were measured in group III (20.99 ± 2.32 MPa). The SBS was significantly lower in groups I and II than in group III (P < .001). The lowest values for SBS were measured in group II (6.42 ± 0.81 MPa). SBS was significantly higher in group I than in group II (P < .001).Conclusions:Both of the bleaching methods significantly affected the SBS of orthodontic brackets on human enamel. Bleaching with the home bleaching method affected SBS more adversely than did bleaching with the office bleaching method.     

Ventral Hernia Repair: a Practical Point of View

Purpose: To evaluate the effect of PVP-I liposome hydrogel on intraperitoneal postoperative adhesions. Material and Methods: Thirty Wistar-Albino male rats were randomly divided into three groups. After midline laparotomy, a 1 cm² area of the caecum was abraded with a sterile gauze until subserosal haemorrhage had developed. A 1 χ 1 cm patch of peritoneum located opposite of caecal abrasion was completely dissected. In group 1 (control group, C) adhesion induction was performed and nothing was applied to the wounds. In group 2 and 3, PVP-I solution (3%) (group 2, PI) and PVP-I liposome hydrogel (group 3, PIL) were applied to the caecal abrasion areas and peritoneal defects. Adhesions were classified according to a classification system based on the evaluation of the appearance, extent and strength of the adhesions on postoperative 21^st day.

Results: There was no significant difference of the adhesion scores between the groups (U1 = 45, p > 0.05; U2 = 48, p > 0.05; U3 = 47.5, p > 0.05).

Conclusions: We found that PVP liposome hydrogel did not influence postoperative intraabdominal adhesions and should be further explored for its potential use in various intraabdominal procedures.     

Microvascular and functional changes according to the fundus location of the affected arteriovenous crossing in patients with branch retinal vein occlusion

Purpose:The aim of this study was to evaluate the structural and functional changes occurring in patients with branch retinal vein occlusion (BRVO) according to the distance of the affected arteriovenous (AV) crossing to the centers of the fovea and optic disc by optic coherence tomography angiography (OCTA).Methods:Forty-five patients with unilateral BRVO and 45 age- and sex-matched healthy controls were included in this retrospective observational study. Images of the macula (3 mm × 3 mm) and affected AV crossing sites were obtained by OCTA. The fovea-AV crossing distance (FAVD), optic disc-AV crossing distance (DAVD), and optic disc-fovea distance (DFD) were measured.Results:The FAVD/DFD ratio was positively correlated with the vessel density in the superficial and deep affected hemifields (r = 0.430, P < 0.05 and r = 0.308, P < 0.05, respectively) and negatively correlated with the superficial foveal avascular zone and logarithm of the minimum angle of resolution (logMAR) visual acuity (r = –0.412, P < 0.05 and r = –0.356, P < 0.05, respectively). The DAVD/DFD ratio was not correlated with the logMAR visual acuity, superficial FAZ area or vessel densities in the affected hemifield (all P > 0.05).Conclusion:The affected AV crossing site that was further away from the fovea had better visual acuity and quantitative microvascular parameters in the affected hemifields. However, this correlation was not observed for the distance between the affected AV crossing site and the optic disc.