Asbestos exposure as a cause of immunological stimulation.

Twenty immunological parameters were determined for 37 asbestos-exposed workers with no radiographic pulmonary fibrosis and 132 asbestosis patients, 37 of whom formed a matched referent group for the non-diseased workers. No clear differences between the matched groups were found for the autoantibodies tested, but the prevalence of autoantibodies was increased in both groups in comparison with the prevalence among Finnish blood donor candidates. This phenomenon may reflect a general immunological activity caused by asbestos dust, and this immunological activity may act as an adjuvant in immunisation. The patients revealed a high level of IgA, C3, C4 and alpha-1-antitrypsin. This result indicates that these factors may be related to the development of asbestosis, and could therefore be utilized in the evaluation of diffuse pulmonary fibrosis among workers with asbestos exposure.     

HLA-B18 antigens and protection from pulmonary fibrosis in asbestos workers

HLA antigens were identified in 64 patients with radiographic asbestosis and 37 matched controls with equivalent asbestos exposure but no radiographic pulmonary fibrosis. A high prevalence of HLA-B18, B27 and Cw2 was found in the controls. This result might indicate that the possessors of these HLA antigens are thus protected from the development of diffuse pulmonary fibrosis from asbestos exposure. Signs of susceptibility were not demonstrated. The radiographic severity and progression of asbestosis were not associated with any of the HLA antigens tested.     

PPARβ/δ-agonist GW0742 ameliorates dysfunction in fatty acid oxidation in PSEN1ΔE9 astrocytes

Astrocytes are the gatekeepers of neuronal energy supply. In neurodegenerative diseases, bioenergetics demand increases and becomes reliant upon fatty acid oxidation as a source of energy. Defective fatty acid oxidation and mitochondrial dysfunctions correlate with hippocampal neurodegeneration and memory deficits in Alzheimer's disease (AD), but it is unclear whether energy metabolism can be targeted to prevent or treat the disease. Here we show for the first time an impairment in fatty acid oxidation in human astrocytes derived from induced pluripotent stem cells of AD patients. The impairment was corrected by treatment with a synthetic peroxisome proliferator activated receptor delta (PPARβ/δ) agonist GW0742 which acts to regulate an array of genes governing cellular metabolism. GW0742 enhanced the expression of CPT1a, the gene encoding for a rate-limiting enzyme of fatty acid oxidation. Similarly, treatment of a mouse model of AD, the APP/PS1-mice, with GW0742 increased the expression of Cpt1a and concomitantly reversed memory deficits in a fear conditioning test. Although the GW0742-treated mice did not show altered astrocytic glial fibrillary acidic protein-immunoreactivity or reduction in amyloid beta (Aβ) load, GW0742 treatment increased hippocampal neurogenesis and enhanced neuronal differentiation of neuronal progenitor cells. Furthermore, GW0742 prevented Aβ-induced impairment of long-term potentiation in hippocampal slices. Collectively, these data suggest that PPARβ/δ-agonism alleviates AD related deficits through increasing fatty acid oxidation in astrocytes and improves cognition in a transgenic mouse model of AD.     

Effects of low-frequency magnetic fields on implantation in rats

Effects of 50-Hz sinusoidal magnetic fields (MFs) on embryo implantation, serum 17beta-estradiol, progesterone, testosterone, and melatonin levels, and on estrogen receptor (ER) and progesterone receptor (PgR) densities in the uterus were studied during the preimplantation and implantation periods in rats. Pregnant Wistar rats were exposed to magnetic r.m.s. field strengths of 10 or 100 A/m (13 or 130 microT) or sham-exposed (controls) from day 0 of pregnancy for 24 h/day and killed during light and dark periods between 70 h and 176 h after ovulation. MFs did not influence the mean total number of implantations. The nocturnal mean serum melatonin concentration decreased by 34 and 38% at 10 and 100 A/m, respectively. At the same time, the first embryos, at an early developmental stage, arrived in the uterus in the MF-exposed groups. Serum estradiol and progesterone levels did not significantly change. Nuclear PgR and ER densities in the uterus decreased before implantation and there was an increased incidence of early stage embryos and fewer hatched embryos were found in the uterus at 100 A/m. During the early implantation period, the uterine cytosolic ER/PgR-ratio was increased at 100 A/m and no implants were concomitantly found in uterus. The nuclear ER/PgR-ratio decreased during implantation in both MF-groups due to decreased nuclear ER density. At the same time, 19% and 15% of the embryos (calculated from the corpora luteae) at 10 and 100 A/m, respectively, were yet morulae and not implanted. In summary, the results show that MFs do not impair implantation in rats although there may be some borderline changes in the transport and development of embryos and associated endocrinologic parameters.     

Bone mineral density, body height, and vitamin D receptor gene polymorphism in middle-aged men

BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass. However, the relationship has been controversial. It has been suggested that environmental factors such as physical activity may be one of the many reasons for this controversy.AIM. We investigated the possible interactions of VDR gene polymorphisms and low to moderate intensity exercise on bone mineral density (BMD) in a four-year controlled, randomized intervention trial in 140 middle-aged Finnish men. METHOD: The TaqI, FokI, and ApaI restriction fragment length polymorphism (RFLP)-markers of the VDR gene were evaluated. BMDs of the lumbar spine (L2-L4), femoral neck, and total proximal femur were measured with dual-energy X-ray absorptiometry (DXA). In addition, the relations of the VDR gene polymorphism with bone turnover markers (serum tartrate-resistant acid phosphatase (TRAP) 5b activity and serum osteocalcin concentration) were evaluated. RESULTS: At the randomization, the subjects with the VDR TaqI Tt or tt genotype had a greater body height than the subjects with TT genotype (P=0.001). In addition, the association of VDR TaqI polymorphism with femoral BMD was found. The Tt or tt genotype associated with higher femoral neck values than the TT genotype (P=0.003) at randomization. After adjusting the femoral neck for body height, the association remained (P=0.021). We did not find any association between VDR gene polymorphism and bone turnover markers or any interactions of VDR gene polymorphisms and exercise on BMD. CONCLUSIONS: The TaqI polymorphism may be associated with body height and femoral neck BMD values. The present findings also suggest that the VDR polymorphisms do not modify the effect of regular aerobic exercise on BMD. However, more randomized controlled exercise trials are needed to investigate the role of exercise intensity on VDR gene polymorphisms, and the role of VDR gene polymorphisms on BMD.     

Design and synthesis of a novel L-dopa-entacapone codrug

A novel codrug, in which L-Dopa and entacapone are linked via a biodegradable carbamate spacer to form a single chemical entity, was synthesized and studied kinetically. This carbamate codrug provides adequate stability [t(1/2) = 12.1 h (pH 1.2); 1.4 h (pH 5.0); 1.1 h (pH 7.4)] against chemical hydrolysis but rapidly hydrolyzes to L-Dopa and entacapone in liver homogenate (t(1/2) = 7 min; pH 7.4) at 37 degrees C. The therapeutical potential of this novel codrug is discussed.     

开放式鼓室成形术与乳突根治术治疗慢性化脓性中耳炎的临床分析

目的：探讨开放式鼓室成形术与乳突根治术治疗慢性化脓性中耳炎的临床效果情况。方法分析该院耳鼻喉科2010年10月-2015年1月收治的慢性化脓性中耳炎患者58例临床资料,依据治疗方式的不同进行临床分组,联合治疗组(乳突根治术+开放式鼓室成形术)29例和乳突根治术组29例。结果联合治疗组慢性化脓性中耳炎患者术后外耳道形状变化和临床疗效100%均优于乳突根治术组89.7%,差异有统计学意义(P<0.05)。结论开放式鼓室成形术联合乳突根治术治疗慢性化脓性中耳炎的临床效果明显,值得临床推广应用。     

Determinants of Bone Mineral Density in Middle Aged Men: A Population-Based Study

Osteoporosis is a growing health problem not only in women but also in men. To assess determinants of bone mineral density (BMD) at the spine and proximal femur, a randomly selected sample of 140 Finnish men aged 54–63 years was measured using fan beam dual-energy X-ray absorptiometry. Isometric muscle strength was measured using a computerized measurement system and cardiorespiratory fitness was assessed with maximal oxygen uptake (VO₂max) using breath-by-breath respiratory gas analyses during an incremental bicycle ergometer exercise. Intakes of calcium and energy were estimated using 4-day food records. Smoking habits and alcohol consumption were assessed from an interview and a 4 week diary, respectively. Isometric muscle strength of triceps and biceps brachii, extensors and flexors of thigh and rectus abdominis correlated significantly with BMD (r= 0.18–0.35, p= 0.02–0.000). Calcium intake correlated positively with femoral (r= 0.19–0.28, p= 0.03–0.003), but not with lumbar BMD. In addition, calcium intake adjusted for dietary energy content (mg/MJ) correlated with femoral BMD (r= 0.25–0.36, p= 0.03–0.000). Smoking had no effect on BMD, whereas alcohol intake correlated positively with BMD at L2–L4 (r = 0.19, p= 0.031). In the multiple linear regression analysis adjusted calcium intake predicted BMD in every site measured, while strength of abdominal muscles predicted BMD at Ward’s triangle and femoral neck. Body weight was a predictor of trochanteric BMD. Body height was the best predictor of lumbar and femoral neck area. We conclude that low dietary calcium intake, weak muscle strength and low body weight are risk factors for low BMD in men. Received: 30 August 1999 / Accepted: 29 December 1999