Maternal tobacco smoking and decreased leukocytes, including dendritic cells, in neonates

Maternal smoking in pregnancy is associated with respiratory diseases in the offspring, possibly due to prenatal influences on the developing immune system. We investigated whether maternal smoking in pregnancy was associated with cord blood leukocyte numbers, including precursor dendritic cells, adjusting for concomitant factors. In a prospective healthy birth cohort study, total leukocyte counts were reduced in neonates of smoking mothers [10.7 (8.4-13.0), n=14] compared with nonexposed infants [14.7 (13.7-15.7), n=74, p=0.002] [geometric mean cells x 10(3)/microL (95% confidence interval)]. All leukocyte subsets were decreased, most prominently segmented neutrophils [4.3 (2.8-5.7) versus 6.2 (5.5-6.8), p=0.021], lymphocytes [3.8 (2.9-4.8) versus 5.0 (4.5-5.6), p=0.036], and myeloid precursor dendritic cells [12.7 cells/microL (9.1-17.8) versus 18.3 (15.8-21.2), p=0.055]. These differences persisted after adjustment for possible confounders. Predictors of myeloid precursor dendritic cell numbers in multivariable models were maternal smoking (-5.1 cells/microL, p=0.042), age (-0.5 cells/microL/y, p=0.035), and, marginally, asthma (+8.1 cells/microL, p=0.075). The decrease of all leukocytes in neonates of smoking mothers could be clinically significant and suggests a decreased cell production, increased peripheral recruitment, or retention in bone marrow. Given the importance of dendritic cells in early immune responses, their decrease might reflect an impact of maternal smoking on the developing fetal immune system.     

Day care in relation to respiratory-tract and gastrointestinal infections in a German birth cohort study

AIM: To describe day care attendance in Germany today (in former East and former West Germany). To investigate longitudinally whether children attending day care centres have an increased risk of acquiring common cold, bronchitis, pneumonia, otitis media or diarrhea. METHODS: Questionnaire information was collected when the children in the cohort were 6, 12, 18, 24 months, and 4 and 6 years old. Day care within the first and first 2 years of life was investigated longitudinally with GEE (generalised estimating equations) methods in relation to common cold, bronchitis, pneumonia, otitis media and diarrhea within the first 6 years of life. RESULTS: Day care centre attendance is more common in former East than in former West Germany; this difference is evident even 10-12 years after German reunification. Children attending a day care centre were more likely to have common cold, bronchitis, pneumonia, otitis media and diarrhea within the first 2-3 years of life. With the exception of common cold, from year 4 onwards these associations were not statistically significant anymore and even reversed for some of the infections. CONCLUSIONS: Children attending day care centres were at an increased risk of respiratory and gastrointestinal infections within the first years of life. However, around school age these differences disappeared or even partly reversed.     

A Prospective Randomized Experimental Study to Investigate the Eradication Rate of Endometriosis after Surgical Resection versus Aerosol Plasma Coagulation in a Rat Model

Purpose To investigate the eradication rate of endometriosis after surgical resection (SR) vs. thermal ablation with aerosol plasma coagulation (AePC) in a rat model.Methods In this prospective, randomized, controlled, single-blinded animal study endometriosis was induced on the abdominal wall of 34 female Wistar rats. After 14 days endometriosis was either removed by SR or ablated by AePC. 14 days later the rats were euthanized to evaluate the eradication rate histopathologically. Intervention times were recorded.Results Eradication rate of endometriosis after 14 days did not significantly differ between AePC and SR (p=0.22). Intervention time per endometrial lesion was 22.1 s for AePC and 51.8 s for SR (p<0.0001).Conclusions This study compares the eradication rate of the new aerosol plasma coagulation device versus standard surgical resection of endometriosis in a rat model. Despite being a thermal method, AePC showed equality towards SR regarding eradication rate but with significantly shorter intervention time.     

Mast cell tryptase may modulate endothelial cell phenotype in healing myocardial infarcts

Mast cells and macrophages infiltrate healing myocardial infarcts and may play an important role in regulating fibrous tissue deposition and extracellular matrix remodelling. This study examined the time-course of macrophage and mast cell accumulation in healing infarcts and studied the histological characteristics and protease expression profile of mast cells in a canine model of experimental infarction. Although macrophages were more numerous than mast cells in infarct granulation tissue, macrophage density decreased during maturation of the scar, whereas mast cell numbers remained persistently elevated. During the inflammatory phase of infarction, newly recruited leucocytes infiltrated the injured myocardium and appeared to be clustered in close proximity to degranulating cardiac mast cells. During the proliferative phase of healing, mast cells had decreased granular content and were localized close to infarct neovessels. In contrast, macrophages showed no selective localization. Mast cells in healing canine infarcts were alcian blue/safranin-positive cells that expressed both tryptase and chymase. In order to explain the pro-inflammatory and angiogenic actions of tryptase--the major secretory protein of mast cells--its effects on endothelial chemokine expression were examined. Chemokines are chemotactic cytokines that play an important role in leucocyte trafficking and angiogenesis and are highly induced in infarcts. Tryptase, a proteinase-activated receptor (PAR)-2 agonist, induced endothelial expression of the angiogenic chemokines CCL2/MCP-1 and CXCL8/IL-8, but not the angiostatic chemokine CXCL10/IP-10. Endothelial PAR-2 stimulation with the agonist peptide SLIGKV induced a similar chemokine expression profile. Mast cell tryptase may exert its angiogenic effects in part through selective stimulation of angiogenic chemokines.     

Clinical profiling of recombinant follicle stimulating hormone (rFSH; Puregon): relationship between serum FSH and efficacy

Single-dose and multiple-rising dose studies of recombinantfollicle stimulating hormone (rFSH) in hypogonadotrophic maleand female volunteers demonstrated that the rate of FSH absorptionafter i.m. injection is higher in men than in women. In theabsence of endogenous FSH, a correlation between serum FSH andbody weight became apparent. The elimination half-life of rFSHwas not different between the sexes and was comparable withurinary FSH. However, the in-vitro bio:immuno ratio of serumFSH was significantly higher after the administration of rFSHthan after urinary FSH. When rFSH was administered daily witha fixed dose, steady state levels were reached within 3-5 days.Serum FSH concentrations increased in a dose-dependent mannerwhen the daily dose was increased weekly over 3 weeks from 75to 225 IU. In hypogonadotrophic women, rFSH induced normal folliculargrowth whereas oestrogen synthesis was impaired. In women pituitarysuppressed by a high-dose oral contraceptive, the daily administrationof 150 IU rFSH for 1 week induced more and larger antral folliclesthan the same regimen with urinary FSH, whereas the serum immunoactiveFSH concentrations measured 24 h after each dosing were similar.It is concluded that even though equal or lower serum immunoactiveFSH concentrations were obtained following the administrationof rFSH compared with urinary FSH, circulating bioactivity FSHconcentrations were higher. Therefore, the conventional ideathat serum immunoreactive FSH correlates positively with themagnitude of the ovarian response should be reconsidered.     

Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism.

Chromosomal region 15q11-q13 has been implicated to harbor a susceptibility gene or genes underlying autism. Evidence has been derived from the existence of cytogenetic anomalies in this region associated with autism, and the report of linkage in a modest collection of multiplex families. Most recently, linkage disequilibrium with the marker GABRB3-155CA2 in the candidate locus GABRB3, located in this region, has been reported. We searched for linkage using eight microsatellite markers located in this region of chromosome 15 in 147 affected sib-pairs from 139 multiplex autism families. We also tested for linkage disequilibrium in the same set of families with the same markers. We found no evidence for excess allele sharing (linkage) for the markers in this region. Also, we found no evidence of linkage disequilibrium, including for the locus GABRB3-155CA2. Thus, it appears that the role of this region of chromosome 15 is minor, at best, in the majority of individuals with autism.     

Effects of a multi-nutrient supplement on exercise performance and hormonal responses to resistance exercise

The purpose of this study was to determine the influence of a comprehensive multi-component nutritional supplement on performance, hormonal, and metabolic responses to an acute bout of resistance exercise. Nine healthy subjects ingested either Muscle Fuel™ (MF) or a matched placebo (PL) for 7 days. Subjects then reported to the laboratory, ingested the corresponding supplement, and performed two consecutive days of heavy resistance exercise testing with associated blood draws. MF supplementation improved vertical jump (VJ) power output and the number of repetitions performed at 80% of one repetition maximum (1RM). Additionally, MF supplementation potentiated growth hormone (GH), testosterone, and insulin-like growth factor-1 responses to exercise. Concentrations of circulating myoglobin and creatine kinase (CK) were attenuated immediately following resistance exercise during the MF trial, indicating that MF partially mediated some form of exercise-induced muscle tissue damage. In summary MF enhanced performance and hormonal responses associated with an acute bout of resistance exercise. These responses indicate that MF supplementation augments the quality of an acute bout of resistance exercise thereby increasing the endocrine signaling and recovery following heavy resistance exercise.     

Antibiogram and plasmid profiling of carbapenemase and extended spectrum Beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae in Abeokuta,South western,Nigeria

Background

The increased reports of ESBL dissemination from various centres in south western, Nigeria and the recent emergence of carbapenem resistant bacteria prompted the conception of this study.

Objectives

To demonstrate the relationship between high molecular weight plasmids and the expression of antibiotic multi-resistance including ESBL and carbapenemase.

Methods

We investigated 97 isolates of selected organisms consisting of 67 E. coli and 30 Klebseilla spp for the presence of plasmids expressing ESBL including carbapenem-hydrolysing enzymes. Beta-lactamase was determined using acidometric method, while ESBL and carbapenemase activity was determined using the double-disk diffusion test as well as the Modified Hodge test (MHT). Plasmid profiles of ESBL and carbapenemase positive isolates were determined according to standard protocols.

Results

An ESBL prevalence rate of 21.6% and carbapenem- resistance rate of 9.3% was recorded. Antibiotic susceptibility profile of ESBL isolates showed 100.0% resistance against Amoxicillin, Cotrimoxazole and Erythromycin. Moderate susceptibility was recorded against the Quinolone class of antibiotics; Meropenem remained the most active antibiotic against ESBL isolates with 62.5% against E. coli and 60% against K. pneumoniae. The plasmid profiles of our study isolates ranged from 11.8kbp to 35.5kbp.

Conclusion

Due to the relationship between high molecular weight plasmids and multi-drug resistance, we hereby recommend regular molecular surveillance of this form in our study setting.     

Identification of SNPs in the cystic fibrosis interactome influencing pulmonary progression in cystic fibrosis

There is growing evidence that the great phenotypic variability in patients with cysticfibrosis (CF) not only depends on the genotype, but apart from a combination ofenvironmental and stochastic factors predominantly also on modifier gene effects. It hasbeen proposed that genes interacting with CF transmembrane conductance regulator (CFTR)and epithelial sodium channel (ENaC) are potential modifiers. Therefore, we assessed theimpact of single-nucleotide polymorphisms (SNPs) of several of these interacters on CFdisease outcome. SNPs that potentially alter gene function were genotyped in 95well-characterized p.Phe508del homozygous CF patients. Linear mixed-effect model analysiswas used to assess the relationship between sequence variants and the repeatedmeasurements of lung function parameters. In total, we genotyped 72 SNPs in 10 genes.Twenty-five SNPs were used for statistical analysis, where we found strong associationsfor one SNP in PPP2R4 with the lung clearance index (P≤0.01), thespecific effective airway resistance (P≤0.005) and the forced expiratoryvolume in 1 s (P≤0.005). In addition, we identified one SNP inSNAP23 to be significantly associated with three lung function parameters aswell as one SNP in PPP2R1A and three in KRT19 to show a significantinfluence on one lung function parameter each. Our findings indicate that directinteracters with CFTR, such as SNAP23, PPP2R4 and PPP2R1A, may modify the residualfunction of p.Phe508del-CFTR while variants in KRT19 may modulate the amount ofp.Phe508del-CFTR at the apical membrane and consequently modify CF disease.