Morphine and naloxone act similarly on glutamate-caused guinea pig ileum contraction.

Both morphine (M) and naloxone (NL) have been reported to have NMDA receptor blocking effects, regarded as the reason of opiate physical dependence development. On the other hand, glutamate (GLU) has been known to induce the contraction of isolated guinea pig ileum via acetylcholine release. Therefore, different concentrations of M or NL were investigated on the 1 mM GLU-induced contraction of isolated guinea pig ileum fixed at a resting tension of 1 g in isolated organ bath. The mean value (359.3 +/- 20 mg) of the GLU-elicited contraction force was significantly reduced (318.4 +/- 19.4) by 25 nM M concentration in the medium. Consequently, 500 and 750 nM M caused further decreases in a rather dose-dependent manner (270.8 +/- 17.4 and 167.8 +/- 16.5 mg, respectively). One micromolar M contraction nearly abolished (8.0 +/- 8.2 mg) the GLU-induced contraction. A similar effect was obtained with the naloxone concentrations of 10, 20, 40, and 50 microM. In addition, NL has been shown to elicit the contraction of the isolated M-dependent guinea pig ileum. In the present study, 20- and 30-microM NL concentrations in the bathing medium caused the contraction of the ileum made M-dependent by preincubation with M (333.0 +/- 32.4 and 309.5 +/- 17.7 mg, respectively). These contraction forces were significantly reduced when the NL concentration was increased to 40 microM. And, 50 microM NL concentration not only failed to induce contraction but caused a relaxation (-10.6 +/- 2.3) as well. The results were considered supporting evidence for the fact that both M and NL are NMDA receptor blockers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sodium Hydroxide Chemical Matricectomy for the Treatment of Ingrown Toenails: Comparison of Three Different Application Periods

Objective Sodium hydroxide matricectomy is a successful method for the treatment of ingrown toenails. This study was designed to evaluate the optimal sodium hydroxide application period providing high success rates with minimal postoperative morbidity.
Materials and Methods Sixty-six patients with 225 ingrown nail edges were treated in three groups receiving 30-second, 1-minute, and 2-minute applications of sodium hydroxide. Each patient was reviewed postoperatively for pain, drainage, and tissue damage. The median long-term follow-up period was 14 months.
Results The success rate of the therapy was 70.9% in the first group, 92.7% in the second group, and 94.4% in the third group. In all groups, about half of the patients experienced minimal pain within 48 hours following the operation, but only in the third group, 20% of the patients had minimal pain, which continued about 1 week. Drainage and tissue damage were minimal or mild in all groups and disappeared within 3 weeks in the first and second groups but were prolonged to 6 weeks in the third group.
conclusion The success rate of 30-second application is significantly lower than 1-minute and 2-minute applications. Although the success rates of the latter two procedures are similar, the prolonged healing time is the disadvantage of the 2-minute application. We conclude that 1-minute application of 10% sodium hydroxide is simple, safe, and highly effective for the treatment of ingrown nails.     

Effects of probucol in hyperlipidemic rabbit liver: a preliminary ultrastructural study

Probucol is a lipid-lowering agent with an antioxidant effect; however, its influence on the liver remains unclear. The effects of probucol on hyperlipidemic rabbit liver are investigated to add a structural data on its therapeutical profile. Local albino rabbits were divided into three groups. 1) Hyperlipidemic group: fed with 1% cholesterol (150 g/kg/day) enriched chow for 2 months. 2) Probucol treated group: group 1 + intraperitoneal probucol (10 mg/kg/day) administration for 15 days. 3) Control group fed with normal chow. The blood lipid profile was investigated biochemically. Liver samples were examined electronmicroscopically. Within the parenchymal cells of group 1, the amount of rough surfaced endoplasmic reticulum was increased, its cisterna was dilated displaying a moderately electron dense substance in it and showed close apposition with the condensed mitochondria. In group 2, smooth surfaced endoplasmic reticulum was in extensive amounts filling almost all of the cytoplasm, displayed a reticular, degenerated appearance and was in close relation with the condensed, degenerated mitochondria. Probucol may cause degenerative changes on the liver parenchyme at the subcellular level. It alters the structure of these cells mainly acting on the smooth surfaced endoplasmic reticulum and the mitochondria that are known to be involved in cellular detoxification.     

Functional characterization of human natural killer cells responding to Mycobacterium bovis bacille Calmette-Guérin

The kinetics of activation and induction of several effector functions of human natural killer (NK) cells in response to Mycobacterium bovis bacille Calmette-Guérin (BCG) were investigated. Owing to the central role of monocytes/macrophages (MM) in the initiation and maintenance of the immune response to pathogens, two different experimental culture conditions were analysed. In the first, monocyte-depleted nylon wool non-adherent (NW) cells from healthy donors were stimulated with autologous MM preinfected with BCG (intracellular BCG). In the second, the NW cells were directly incubated with BCG, which was therefore extracellular. In the presence of MM, CD4+ T lymphocytes were the cell subset mainly expressing the activation marker, CD25, and proliferating with a peak after 7 days of culture. In contrast, in response to extracellular BCG, the peak of the proliferative response was observed after 6 days of stimulation, and CD56+ CD3- cells (NK cells) were the cell subset preferentially involved. Such proliferation of NK cells did not require a prior sensitization to mycobacterial antigens, and appeared to be dependent upon contact between cell populations and bacteria. Following stimulation with extracellular BCG, the majority of interferon-gamma (IFN-gamma)-producing cells were NK cells, with a peak IFN-gamma production at 24-30 hr. Interleukin (IL)-2 and IL-4 were not detectable in NK cells or in CD3+ T lymphocytes at any time tested. IL-12 was not detectable in the culture supernatant of NW cells stimulated with extracellular BCG. Compared to the non-stimulated NW cells, the NW cells incubated for 16-20 hr with BCG induced the highest levels of expression of apoptotic/death marker on the NK-sensitive K562 cell line. BCG also induced expression of the activation marker, CD25, and proliferation, IFN-gamma production and cytotoxic activity, on negatively selected CD56+ CD3- cells. Altogether, the results of this study demonstrate that extracellular mycobacteria activate several NK-cell functions and suggest a possible alternative mechanism of NK-cell activation as the first line of defence against mycobacterial infections.     

Human NK1 and NK2 subsets determined by purification of IFN-gamma-secreting and IFN-gamma-nonsecreting NK cells

The in vivo existence of human NK cell subsets similar to Th1 and Th2 cells was demonstrated in freshly isolated IFN-gamma-secreting and IFN-gamma-nonsecreting NK cells. The IFN-gamma-secreting NK subset showed a typical cytokine pattern with predominant expression of IFN-gamma, but almost no IL-4, IL-5 and IL-13. In contrast, the IFN-gamma-nonsecreting NK subset was composed of IL-4, IL-5 and IL-13-producing NK cells. Short-time stimulation or 2 weeks of in vitro differentiation of NK cells led to distinct patterns of cytokine production similar to freshly-purified IFN-gamma (+) or IFN-gamma (-) NK cell subsets. NK cells stimulated with IL-12 produced increased levels of IFN-gamma and decreased levels of IL-4. In contrast, stimulation of NK cells with IL-4 inhibited IFN-gamma, but increased IL-13 production. Freshly-purified IFN-gamma (+) and IFN-gamma (-) or in vitro differentiated NK1 and NK2 subsets showed similar cytotoxicity to K562 cells. These results demonstrate that circulating NK cells retain effector subsets in humans with distinct cytokine profiles and may display different inflammatory properties.     

Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow

Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1α are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin–biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK⁺ cells was 236 (range, 20–847) per 5 × 10⁴ enriched BM cells. The presence of CK⁺ cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (>236 CK⁺ per 5 × 10⁴ enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.     

Lung function status of some Nigerian men and women chronically exposed to fish drying using burning firewood

OBJECTIVE: To determine the lung function status of some Nigerian men and women chronically exposed to fish drying using burning firewood. DESIGN: Case control study. SETTING: Ibaka, Utaewa and Ikanga fishing settlements. SUBJECTS: 183 males and 192 females engaged in fishing, aged 20 to 45 years who have been exposed for a minimum of five years as cases. The control group comprised sex matched male (142) and female (152) Nigerians from the same area who were not exposed to any known air pollutant. MAIN OUTCOME MEASURES: Lung function indices: FVC, FEV1, FEV1% and PEFR. RESULTS: Lung function indices were significantly lower in men engaged in fishing than in their controls: FVC [mean (SD): 2.98 (0.20) vs 3.52 (0.29), p < 0.001]; FEV1 [2.08 (0.18) vs 2.82 (0.25), p < 0.001]; FEV1% [69.8 (3.1) vs 80.2 (6.7), p < 0.001]; and PEFR [335 (22) vs 592 (99), p < 0.001], respectively. Similarly, lung function indices were lower in females in the fishing industry than in their controls; FVC [2.42 (0.17) vs 3.02 (0.24), p < 0.001]; FEV1 [1.70 (0.19) vs 2.55 (0.21), p < 0.001]; FEV1% [72.9 (3.2) vs 84.4 (6.7), p < 0.001]; and PEFR [298 (22) vs 418 (34), p < 0.001]. All the lung function indices (except FEV1%) of the fishermen and women declined significantly (p < 0.001) with their duration of exposure. The results showed a predominantly mixed pattern (restrictive and obstructive) of respiratory defect. There were higher prevalences of respiratory and other symptoms among the cases than the controls. The respiratory symptoms included cough with sputum, chest pain, dyspnoea catarrh and sneezing and unproductive cough. Other symptoms were eye and skin irritation, internal heat and headache. CONCLUSIONS: Chronic exposure to fish drying using burning firewood can impair lung function and cause respiratory and other symptoms.     

The Manchester operation for uterine prolapse.

OBJECTIVE: To evaluate the clinical characteristics, complications, and satisfaction scores of patients who underwent the Manchester operation. METHODS: This retrospective observational study evaluated data from 204 women who underwent the Manchester operation at the Department of Obstetrics and Gynecology of Hacettepe University School of Medicine, Ankara, Turkey, from January 1985 to April 2004. RESULTS: Mean age was 34.68+/-4.24 years and parity 2.47+/-0.96; 85.8% of the patients were premenopausal; 176 patients (86.28%) had grade 3 and 28 (13.72%) had grade 2 uterine prolapse; 95.1% of the patients had associated cystoceles and 51.3% had associated rectoceles; and 81.4% had urinary incontinence. Regarding early postoperative complications, 27 patients (13.23%) had febrile morbidity; retroperitoneal hematoma occurred in 1 patient (0.49%); urinary retention occurred in 45 patients (22.05%), and cervical stenosis occurred in 23 patients (11.27%). At 1 year, 1 patient had undergone abdominal hysterectomy because of unsuccessful cervical dilatation; and a mean of 3.6 years following the operation, 8 patients (3.9%) had undergone the tension-free vaginal tape procedure plus a vaginal hysterectomy for recurrent stress urinary incontinence and uterine prolapse. The mean satisfaction/acceptance score for the operation was 8.52+/-2.13 (range, 2-10). CONCLUSION: A high degree of acceptance/satisfaction and a low morbidity rate show the Manchester operation to be a good option for the treatment of uterine prolapse in women who wish to keep their uterus.     

Avaliação do Nível de Fluxo Coronário com MOTS-C em Pacientes com IAMCSST Submetidos à ICP Primária

BackgroundThe protective effects of mitochondrial open reading frame of the 12S rRNA-c (MOTS-C) on cardiovascular diseases have been shown in numerous studies. However, there is little documentation of the relationship between MOTS-C and coronary blood flow in ST-segment elevation myocardial infarction (STEMI).ObjectiveWe aimed to investigate the role of MOTS-C, which is known to have cytoprotective properties in the pathogenesis of the no-reflow phenomenon, by comparing the coronary flow rate and MOTS-C levels in patients with STEMI submitted to primary PCI.Methods52 patients with STEMI and 42 patients without stenosis >50% in the coronary arteries were included in the study. The STEMI group was divided into two groups according to post-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade:(i) No-reflow: grade 0, 1, and 2 and (ii) grade 3(angiographic success). A p value of <0.05 was considered significant.ResultsMOTS-C levels were significantly lower in the STEMI group compared to the control group (91.9 ± 8.9 pg/mL vs. 171.8±12.5 pg/mL, p<0.001). In addition, the Receiver Operating Characteristics (ROC) curve analysis indicated that serum MOTS-C levels had a diagnostic value in predicting no-reflow (Area Under the ROC curve [AUC]:0.95, 95% CI:0.856-0.993, p<0.001). A MOTS-C ≥84.15 pg/mL measured at admission was shown to have 95.3% sensitivity and 88.9% specificity in predicting no-reflow.ConclusionMOTS-C is a strong and independent predictor of no-reflow and in-hospital MACE in patients with STEMI. It was also noted that low MOTS-C levels may be an important prognostic marker of and may have a role in the pathogenesis of STEMI.