Pulmonary function and bronchial reactivity in asthmatics during low-level formaldehyde exposure

This study evaluated whether formaldehyde, at concentrations similar to those found in the indoor environment, could produce adverse effects on the lower airway of 15 asthmatic persons with documented bronchial hyperresponsiveness who were exposed for 90 min in a climate chamber to clean air containing formaldehyde vapor at levels of 0.85 mg/m3, 0.12 mg/m3, and 0.008 mg/m3. No significant changes in forced expiratory volume in 1 sec (FEV1), airway resistance (Raw), specific airway resistance (SRaw), and flow-volume curves could be detected during formaldehyde exposure. Furthermore, histamine challenge tests performed immediately after formaldehyde exposure showed no evidence of changes in bronchial reactivity. No late reactions were registered during the first 14-16 hr after exposure. The results suggest that residential levels of formaldehyde are of minor importance in the emergence of pulmonary symptoms. Discrepancies between the present study and previous data may be due to differences in environmental conditions.     

Effect of digoxin on coronary blood flow and myocardial oxygen consumption in patients with chronic coronary artery disease

In 10 patients with chronic coronary artery disease and without clinical evidence of congestive heart failure, the effects of 1.0 mg of digoxin intravenously on systemic hemodynamics, coronary blood flow, myocardial oxygen consumption and myocardial lactate extraction were studied both at rest and during atrial pacing. Atrial stimulation at a rate just below the threshold for angina led to a significant decrease in left ventricular enddiastolic pressure, from 10.6 ± 1.6 to 7.1 ± 0.8 mm Hg, associated with a significant decrease in left ventricular stroke work index per beat, from 76.7 ± 5.11 to 40.3 ± 4.01 g-m/m². After digoxin, nearly identical results in stroke work index could be observed at rest and during stimulation (75.2 ± 6.74 and 44.1 ± 5.92, respectively). However, left ventricular enddiastolic pressure decreased significantly before and during atrial stimulation (8.1 ± 1.29 and 4.7 ± 1.09 mm Hg, respectively). Cardiac index decreased from 3.08 ± 0.20 to 2.73 ±0.17 liters/min per m² at rest but during pacing it no longer differed before and after digoxin (3.17 ± 0.22 and 3.10 ± 0.20 liters/min per m², respectively). Myocardial oxygen consumption and lactate extraction remained unchanged after digoxin both at rest and during atrial pacing.It is concluded that some deficiency in left ventricular function is present in patients with chronic coronary artery disease even without clinical evidence of congestive heart failure. Digoxin improves left ventricular performance at rest and during stress conditions. An expected increase in myocardial oxygen consumption due to enhanced contractility is completely counterbalanced, probably by a decrease in left ventricular volume after digoxin.     

Pelvic Nerve Stimulation Evokes Nitric Oxide Mediated Distal Rectal Relaxation in Pigs

Purpose  Pelvic nerve stimulation evokes a complex motility response in the pig rectum with a proximal decrease and a distal increase in cross-sectional area. This study investigated whether the distal increase in the cross-sectional area is because of smooth muscle relaxation mediated by nitric oxide. Methods  The pelvic nerves were stimulated with cuff electrodes in ten chloralose-anesthetized minipigs. Pressure, volume, and cross-sectional areas at five positions in the rectum were obtained during stimulation to examine the effect of N^G-nitro-L-arginine (an inhibitor of nitric oxide synthase) injection. Results  Stimulation evoked a median pressure decrease of 13 cm H₂O (range, 0–27; P < 0.05; n = 10) in the anal canal, a pressure increase of 6 cm H₂O (range,-15 to 30; P < 0.05; n = 10) in the rectum and a decrease of 39 mL (range, 30–63; P < 0.05; n = 6) in rectal volume. Rectal cross-sectional areas decreased 33 percent (range, 5–56; P < 0.02; n = 7) in the proximal part and increased 32 percent (range, 9–67; P < 0.02; n = 8) in the distal part. N^G-nitro-L-arginine eliminated the increase in the distal rectal cross-sectional area (n = 5) and the decrease in anal canal pressure (n = 9) in all tested animals. Conclusion  Pelvic nerve stimulation evokes distal rectal relaxation in pigs, sensitive to N^G-nitro-L-arginine, which suggests that this smooth muscle response is mediated by nitric oxide. This work was supported by grants from the Institute of Experimental Clinical Research, Aarhus University Hospital, Aarhus, Denmark Reprints are not available.     

A comparative study on alcohol-preferring rat lines: effects of deprivation and stress phases on voluntary alcohol intake

BACKGROUND: Voluntary alcohol intake in rats can be influenced by alcohol deprivation phases and stress. We investigated the magnitude of the effects of both deprivation and stress (forced swimming in cold water and foot-shock had been chosen as stressors distinct in their physical and psychological features) on alcohol intake and the influence of these experiences on the time course of alcohol drinking behavior. For the alcohol drinking procedure, a long-term model of alcohol self-administration originally developed for heterogeneous Wistar rats was used and was compared with different alcohol-preferring rat lines. METHODS: Adult male Alko alcohol (AA), alcohol-preferring (P), high-alcohol-drinking (HAD), and unselected Wistar rats were given ad libitum access to water, 5%, and 20% alcohol solutions for 6 months. A deprivation phase of 14 days was performed after 8 weeks of access to alcohol. After 16 weeks and 22 weeks of alcohol access, all animals were subjected to forced swimming and foot-shock, respectively, for 3 consecutive days, while alcohol intake was still being measured. RESULTS: Alcohol deprivation led to a significant increase in alcohol intake in Wistar rats and P rats. No alcohol deprivation effect was observed in HAD and AA rats; after deprivation, however, their preference for the 20% alcohol solution increased, immediately in the HAD rats and gradually over time in the AA rats. Repeated swim stress caused an increase in alcohol intake in Wistar rats but no changes in the alcohol-preferring rat lines. Foot-shock stress increased alcohol consumption in all lines of rats, but the most pronounced effects were observed in HAD and P rats. CONCLUSIONS: Wistar, HAD, P, and AA rats differentially respond to alcohol deprivation and stress, showing that the genetic background of these different rat lines profoundly affects relapse-like drinking and stress-induced drinking.     

白细胞介素1基因多态性与北京地区胃癌的关系

目的　了解白细胞介素 (IL) 1β 31、IL 1β 5 11和IL 1受体拮抗因子基因 (IL 1RN)多态性在北京地区胃癌患者及慢性胃炎患者中的分布情况 ,探讨IL 1基因多态性与北京地区胃癌的关系。方法　收集北京地区 5 7例胃癌患者和 12 0例慢性胃炎患者的外周血标本 ,提取DNA ,用聚合酶链反应 限制性片段长度多态性法 (PCR RFLP)检测入选患者的IL 1基因多态性情况 ,并比较这些基因多态性在胃癌组和慢性胃炎组的分布差异。结果　IL 1β 31C等位基因在慢性胃炎组和胃癌组中的分布频率分别为 4 9.2 %和 6 1.4 % ,胃癌组明显高于慢性胃炎组 (P <0 .0 5 ) ,携带IL 1β 31C等位基因增加胃癌的风险性 ,IL 1β 31C/C纯合子型的胃癌风险OR值为 2 .4 (95 %CI =1.0～ 5 .9)。IL 1β 5 11T等位基因在慢性胃炎组和胃癌组中的分布频率分别为 4 7.9%和 6 5 .8% ,胃癌组明显高于慢性胃炎组 (P <0 .0 1) ,携带IL 1β 5 11T等位基因增加胃癌的风险性 ,IL 1β 5 11T/T纯合子型的胃癌风险OR值为 3.8(95 %CI =1.5～ 9.7)。IL 1RN 2等位基因在慢性胃炎组和胃癌组中的分布频率分别为 3.8%和 11.4 % ,胃癌组明显高于慢性胃炎组 (P <0 .0 1) ,携带IL 1RN 2等位基因增加胃癌的风险性 ,L/ 2杂合子型的胃癌风险OR值为 3.5 (95 %CI =1.4～ 8.9     

DNA聚合酶β活力测定在肺癌诊疗中的意义

DNA聚合酶β是一种重要的DNA修复酶,它在肿瘤诊断和治疗中的意义近年来才被人们关注。本文通过选用DNA聚合酶专一性抑制剂和~3H—TTP掺入法,测定了25例肺癌患者外周血淋巴细胞中DNA聚合酶β的活力,并与同期收治的14例肺结核病人相对照,旨在探讨测定该酶活力在肺癌诊断、鉴别诊断和治疗中的意义。结果显示,肺癌病人外周血淋巴细胞中DNA聚合酶β活力明显高于肺结核病人(P<0.05),这种现象在不同年龄肺癌病人(33～81岁)中均存在;化疗1至2周内,该酶活力出现下降(P<0.05),化疗后3周时仍有下降趋势,并且下降越明显,疗效越好。上述结果表明,肺癌病人外周血淋巴结胞DNA聚合酶β活力有异常升高,这对肺癌的诊断或鉴别诊断有一定辅助意义。同时也提示,通过分析肺癌病人化疗前后DNA聚合酶β活力,可能有助于对病人的疗效分析。化疗以后,该酶活力下降越多,肺癌的DNA修复能力削弱就越重,疗效相对较好。     

Single‐dose administration of clenbuterol is detectable in dried blood spots

Clenbuterol is a β₂‐agonist prescribed for asthmatic patients in some countries. Based on its anabolic and lipolytic effects observed in studies on rodents and in livestock destined for food production, clenbuterol is abused by bodybuilders and athletes seeking leanness. Urinary clenbuterol analysis is part of routine doping analysis. However, the collection of urine samples is time‐consuming and can be intimidating for athletes. Dried blood spot (DBS) appears attractive as an alternative matrix, but the detectability of clenbuterol in humans through DBS has not been investigated. This study evaluated if clenbuterol could be detected in DBS and urine collected from six healthy men after oral intake of 80 μg clenbuterol. The DBS and urine samples were collected at 0, 3, 8, 24, and 72 h post‐ingestion, with additional urine collections on days 7 and 10. Using LC–MS/MS, it was shown that clenbuterol could be detected in all DBS samples for 24 h post‐ingestion and with 50% sensitivity 3 days after ingestion. The DBS method was 100% specific. Evaluation of analyte stability showed that clenbuterol is stable in DBS for at least 365 days at room temperature when using desiccant and avoiding light exposure. In urine, clenbuterol was detectable for at least 7–10 days after ingestion. Urinary clenbuterol concentrations below 5 ng/mL were present in some subjects 24 h after administration. Collectively, these data indicate that DBS are suitable for routine doping control analysis of clenbuterol with a detection window of at least 3 days after oral administration of 80 μg.     

Reduced Mortality After Oral Polio Vaccination and Increased Mortality After Diphtheria-tetanus-pertussis Vaccination in Children in a Low-income Setting

PurposeThe diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV) were introduced in children 3 of 5 months of age in 1981–1983 in Bandim, in the capital of Guinea-Bissau. Because DTP has been linked to deleterious nonspecific effects (NSEs) and OPV to beneficial NSEs, we followed up this cohort to 3 years of age and examined the effects of DTP with OPV on all-cause mortality and the interactions of DTP and OPV with the measles vaccine (MV).MethodsDTP and OPV were offered at 3 monthly community weighing sessions. Vaccination groups were defined by the last vaccine received. We compared overall mortality for different groups in Cox proportional hazards regression models, reporting hazards ratios (HRs) with 95% CIs.FindingsThe study cohort included 1491 children born in Bandim from December 1980 to December 1983. From 3 to 35 months of age, with censoring for MV, children vaccinated with DTP and/or OPV had higher mortality than both unvaccinated children (HR = l.66; 95% CI, 1.03–2.69) and OPV-only vaccinated children (HR = 2.81; 95% CI, 1.02–7.69); DTP-only vaccinated children had higher mortality than OPV-only vaccinated children (HR = 3.38; 95% CI, 1.15-–9.93). In the age group of 3–8 months, before MV is administered, DTP-only vaccination was associated with a higher mortality than DTP with OPV (HR = 3.38; 95% CI, 1.59–7.20). Between 9 and 35 months of age, when MV is given, DTP-vaccinated and MV-unvaccinated children had higher mortality (HR = 2.76; 95% CI, 1.36–5.59) than children who had received MV after DTP, and among children who received DTP with MV or after MV, DTP-only vaccination was associated with a higher mortality than DTP with OPV (HR = 6.25; 95% CI, 2.55–15.37).ImplicationsBecause the 2 vaccines had differential effects and the healthiest children were vaccinated first, selection biases are unlikely to explain the estimated impact on child survival. OPV had beneficial NSEs, and administration of OPV with DTP may have reduced the negative effects of DTP.     

Regulation of NKG2D-ligand cell surface expression by intracellular calcium after HDAC-inhibitor treatment

In this study we demonstrate that histone deacetylase (HDAC)-inhibitor mediated cell surface expression of the structural different NKG2D-ligands MICA/B and ULBP2 is calcium-dependent. Treatment with the calcium chelator EGTA inhibited constitutive as well as HDAC-inhibitor induced MICA/B and ULBP2 cell surface expression on melanoma cells and Jurkat T-cells. A NKG2D-dependent cytolytic assay and staining with a recombinant NKG2D-Fc fusion protein showed that calcium chelation impaired the functional ability of NKG2D-ligands induced by HDAC-inhibitor treatment.The HDAC-inhibitor induced cell surface expression of ULBP2, but not MICA/B, was sensitive to treatment calmidazolium and trifluoperazine, two agents known to block calcium signaling. siRNA-mediated knock-down of the calcium-regulated proteins calmodulin or calpain did however not affect NKG2D-ligand cell surface expression on Jurkat T-cells. We further show that secretion and cell surface binding of the calcium-regulating protein galectin-1 is enhanced upon HDAC-inhibitor treatment of melanoma cells. However, binding of galectin-1 to cell surface glycoproteins was not critical for constitutive or HDAC-inhibitor induced MICA/B and ULBP2 cell surface expression.We provide evidence that MICA/B and ULBP2 cell surface expression is controlled differently by calcium, which adds to the increasing perception that cell surface expression of MICA/B and ULBP2 is controlled by distinct signal transduction pathways.     

MALDI Biotyper-Based Rapid Resistance Detection by Stable-Isotope Labeling

Against the background of increasing numbers of resistant microorganisms, the fast and cost-efficient detection of microbial resistance is an important clinical requirement for optimal therapeutic intervention. Current routine assays take at least 5 h, but in most cases an overnight incubation is necessary to identify resistant isolates. The usage of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) profiling in combination with growth media containing isotopically labeled amino acids facilitates the detection of resistant microorganisms after 3 h or less directly from the profile spectrum. Growing microorganisms incorporate isotopically labeled amino acids, increasing protein masses and thereby leading to mass shifts of their corresponding peaks in the profile spectra. In the presence of antibiotics, only resistant microorganisms are able to grow and to incorporate the labeled amino acids. This leads to a difference in the mass spectra of susceptible and resistant isolates, allowing their differentiation. In the presented study, we demonstrated the applicability of this novel approach for the detection of methicillin-resistant Staphylococcus aureus and tested different bioinformatics approaches for automated data interpretation.