Metabolic studies of salbutamol-H: A new bronchodilator,in rat,rabbit, dog and man

Salbutamol-³H, labelled on the β-carbon atom, was rapidly absorbed from the gastro-intestinal tract of rat, rabbit, dog and man. 60–90%, depending upon the species studied, of the administered radioactivity was recovered in the 24 hr urine. 70–90% of the radioactivity present in the dog urine was due to unchanged salbutamol-³H, whereas 90% in the rabbit and 40% in the rat urine was due to salbutamol-³H o-phenylglucuronide. The latter has been isolated and shown to be neither a β-stimulant nor a β-blocker. The rat conjugated salbutamol-³H in the liver, and excreted the glucuronide via the bile. 0–48 hr rat faeces contained 25–40% of the label. Analysis of the tissues from the rat and dog indicated that the drug was completely cleared from the body. Salbutamol-³H inhaled by dogs and humans as an aerosol was slowly adsorbed from the lung, and excreted via the urine.     

Neurodevelopmental toxicity of methylmercury: Laboratory animal data and their contribution to human risk assessment

Methylmercury (MeHg) is one of the most significant public health hazards. The clinical findings in the victims of the Japanese and Iraqi outbreaks have disclosed the pronounced susceptibility of the developing brain to MeHg poisoning. This notion has triggered worldwide scientific attention toward the long-term consequences of prenatal exposure on child development in communities with chronic low level dietary exposure. MeHg neurodevelopmental effects have been extensively investigated in laboratory animals under well-controlled exposure conditions. This article provides an updated overview of the main neuromorphological and neurobehavioral changes reported in non-human primates and rodents following developmental exposure to MeHg. Different aspects of MeHg's effects on the immature organism are reported, with particular reference to the delayed onset of symptoms and the persistency of central nervous system (CNS) injury/dysfunction. Particular attention is paid to the comparative toxicity assessment across species, and to the degree of concordance/discordance between human and animal data. The contribution of animal studies to define the role of potential effect modifiers and variables on MeHg dose-response relationships is also addressed. The ultimate goal is to discuss the relevance of laboratory animal results, as a complementary tool to human data, with regard to the human risk assessment process.     

Hormonal regulation of longevity in mammals

Multiple biological and environmental factors impact the life span of an organism. The endocrine system is a highly integrated physiological system in mammals that regulates metabolism, growth, reproduction, and response to stress, among other functions. As such, this pervasive entity has a major influence on aging and longevity. The growth hormone, insulin-like growth factor-1 and insulin pathways have been at the forefront of hormonal control of aging research in the last few years. Other hormones, including those from the thyroid and reproductive system have also been studied in terms of life span regulation. The relevance of these hormones to human longevity remains to be established, however the evidence from other species including yeast, nematodes, and flies suggest that evolutionarily well-conserved mechanisms are at play and the endocrine system is a key determinant.     

Effect of Sexual Maturity on Testicular Injury Subsequent to Procarbazine Administration in Rats

The present study examined the effect of age on various aspects of Leydig cell and Sertoli cell function in Sprague-Dawley rats administered procarbazine. Procarbazine was administered intraperitoneally to Sprague-Dawley rats aged 14, 24, and 60 days in 3 weekly injections of 200 mg/kg. Animals were sacrificed 1 week after the last injection. Severe impairment of spermatogenesis was evident in all animals. Sertoli cell function, as assessed by total testicular ABP content, was not significantly different between procarbazine-treated animals and controls in any age group. On the other hand, procarbazine administration resulted in a 60% reduction in total intratesticular testosterone content in the 14-day-old rats but not in the 24- or 60-day-old animals. Serum testosterone was significantly reduced by 50% in the group of 14-day-old animals but not in the other age groups. Serum LH values were not significantly changed from control levels in any age group. Testicular content of Fe, Zn, Mn, and Cn were unaltered by procarbazine administration in any age group. Since serum LH and testicular cation content were not affected by procarbazine treatment, the significant decreases in serum and testicular testosterone in 14-day-old animals after procarbazine administration may indicate a direct age-dependent effect of procarbazine on Leydig cell function.     

Heightened locomotor-activating effects of amphetamine administered into the nucleus accumbens in adolescent rats

There is a shift in sensitivity to systemically administered psychostimulants in adolescence, as evidenced by less amphetamine-induced locomotor activity in adolescent compared to adult rodents. Locomotor activating effects of amphetamine are dependent on drug actions in the core of the nucleus accumbens (NAc), but the contribution of this region to age differences in amphetamine sensitivity has not been studied directly. In the present study, we investigated the development of the NAc using targeted injections of amphetamine (0, 3, or 6 μg/side) directly into the NAc core in early (postnatal day 30; P30) or late (P45) adolescence, or in adulthood (P75). Locomotor activity was recorded during two 1 h sessions, 48 h apart. Amphetamine increased locomotor activity at all ages. P45 rats were more active than adults only at the 3 μg/side dose, but this difference was not significant when baseline activity was taken into account. In contrast, P30 rats were more active than adults at the 6 μg/side dose, indicating that the magnitude of the locomotor response is highest in early adolescence. Results of the present study are the first to directly show a developmental difference in the sensitivity of the NAc to amphetamine under conditions in which the influence of pharmacokinetic factors and regulatory brain regions is minimized.     

Analysis of Immune Privilege in Eyes with Mycobacteria tuberculosa Adjuvant-Induced Uveitis

Purpose: To examine the effects of intravitreal Mycobacteria tuberculosa adjuvant (MTA) on ocular immune privilege. Methods: MTA was injected into the vitreous cavity of BALB/c mouse eyes to induce anterior uveitis. The inflamed eyes were then examined for their capacity to afford immune privilege to injected allogeneic tumor cells and to promote anterior chamber-associated immune deviation (ACAID). Aqueous humor (AqH) was tested for IL-12 content and for its ability to inhibit T-cell activation. Results: AqH removed from MTA-inflamed eyes at 6 and 12 h contained high levels of IL-12, which then fell almost to baseline at 24 h. This is relevant to the finding that the inflamed eye failed to support ACAID induction at an early time period and then regained the ACAID-induction capability at a later time. Nonetheless, AqH removed from MTA-inflamed eyes retained its capacity to suppress T-cell activation, and MTA-inflamed eyes afforded extended survival to alloantigenic tumor cells implanted into the anterior chamber. Conclusion: Intraocular inflammation evoked by MTA causes the local accumulation of IL-12 and simultaneously robs the eye of its capacity to promote systemic immune tolerance to eye-derived antigens. However, MTA-inflamed eyes retain immune privilege, as indicated by their support of the progressive growth of allogeneic tumor cells.     

SCG postnatal remodelling - hypertrophy and neuron number stability - in Spix's Yellow-toothed Cavies (Galea spixii)

Whilst a fall in neuron numbers seems a common pattern during postnatal development, several authors have nonetheless reported an increase in neuron number, which may be associated with any one of a number of possible processes encapsulating either neurogenesis or late maturation and incomplete differentiation. Recent publications have thus added further fuel to the notion that a postnatal neurogenesis may indeed exist in sympathetic ganglia. In the light of these uncertainties surrounding the effects exerted by postnatal development on the number of superior cervical ganglion (SCG) neurons, we have used state-of-the-art design-based stereology to investigate the quantitative structure of SCG at four distinct timepoints after birth, viz., 1-3 days, 1 month, 12 months and 36 months. The main effects exerted by ageing on the SCG structure were: (i) a 77% increase in ganglion volume; (ii) stability in the total number of the whole population of SCG nerve cells (no change - either increase or decrease) during post-natal development; (iii) a higher proportion of uninucleate neurons to binucleate neurons only in newborn animals; (iv) a 130% increase in the volume of uninucleate cell bodies; and (v) the presence of BrdU positive neurons in animals at all ages. At the time of writing our results support the idea that neurogenesis takes place in the SCG of preás, albeit it warrants confirmation by further markers. We also hypothesise that a portfolio of other mechanisms: cell repair, maturation, differentiation and death may be equally intertwined and implicated in the numerical stability of SCG neurons during postnatal development.     

特殊行业鼠类密度调查

目的了解特殊行业鼠密度及控制状况。方法粘鼠板法调查特殊行业鼠类密度及种群和数量,询问各单位控制鼠类措施。结果调查特殊行业106个单位,1 156个房间,布有效粘鼠板1 832块,阳性捕鼠板数量123块,粘捕率为6.71%。共捕鼠136只,粘捕指数为0.0 742只/块。鼠种为褐家鼠(占45.59%)、黄胸鼠(占27.94%)、小家鼠(占20.58%)、黑线姬鼠(占5.88%)。PCO公司预防控制鼠类效果优于单位自行控制效果(χ2=12.58,P<0.01)。新建开业单位鼠密度显著高于非新建开业单位鼠密度(χ2=33.07,P<0.01)。结论特殊行业是鼠类易侵入单位,提倡PCO公司为特殊行业提供鼠类预防控制服务,并应特别加强新建开业单位的开业前鼠类预防控制措施工作。     

Estrogen receptor-β ligand treatment modulates dendritic cells in the target organ during autoimmune demyelinating disease

Estrogens act upon nuclear estrogen receptors (ER) to ameliorate cell-mediated autoimmune disease. As most immunomodulatory effects of estrogens in EAE have been attributed to the function of ER-α, we previously demonstrated that ER-β ligand treatment reduced disease severity without affecting peripheral cytokine production or levels of CNS inflammation, suggesting a direct neuroprotective effect; however, the effect of ER-β treatment on the function of immune cells within the target organ remained unknown. Here, we used adoptive transfer studies to show that ER-β ligand treatment was protective in the effector, but not the induction phase of EAE, as shown by decreased clinical disease severity with the preservation of axons and myelin in spinal cords. The analysis of the immune cell infiltrates in the CNS revealed that while ER-β ligand treatment did not reduce overall levels of CNS inflammation, there was a decrease in the DC percentage, and these CNS DC had decreased TNF-α production. Finally, experiments using DC deficient in ER-β revealed that the expression of ER-β on DC was essential for protective effects of ER-β ligand treatment in EAE. Our results demonstrate for the first time an effect of ER-β ligand treatment in vivo on DC in the target organ of a prototypic cell-mediated autoimmune disease.     

内蒙古鼠疫自然疫源地啮齿动物现况调查

目的总结分析2000-2011年内蒙古各疫源地啮齿动物的种类、数量、分布和染疫情况,为今后的监测和防治提供科学依据。方法收集2000-2011年内蒙古鼠疫监测总结和疫情分析报告,应用Excel2003软件分别对啮齿动物及其感染鼠疫的情况按不同年代、不同疫源地分别进行统计,采用描述性流行病学方法进行分析。结果 2000-2011年,在内蒙古各疫源地共捕获啮齿动物2目6科30种180 301只,其中在长爪沙鼠疫源地获鼠24种78 263只,达乌尔黄鼠疫源地获鼠19种78 638只,蒙古旱獭疫源地获鼠14种3 435只,布氏田鼠疫源地获鼠13种19 967只;从达乌尔黄鼠,布氏田鼠、长爪沙鼠3个类型疫源地的9种啮齿动物体内检出了鼠疫菌共728株,从达乌尔黄鼠,布氏田鼠、长爪沙鼠、蒙古旱獭四个类型的疫源地的7种啮齿动物体内均检出了血凝阳性血清269份。结论内蒙古鼠疫自然疫源地啮齿动物种类多、数量大、分布广,宿主类型复杂,动物鼠疫十分活跃,应加强监测,有的放矢地做好鼠疫的防控工作。