Schistosomiasis: its significance in a changing human ecology.

Schistosomiasis is a man-made disease. Evaluation of the current status of schistosomiasis requires knowledge of the intensity of infection, a measure now dependent on quantitative egg counts and applied to data only on a limited scale. The determinants of intensity of infection are as yet ill-defined. Morbidity and mortality associated with schistosomiasis are difficult to assess in indigenous populations saddled with a multiplicity of diseases. However, the problem of schistosomiasis and its deleterious consequences will rapidly worsen as an expanding population creates new aquatic habitats favorable for the snail intermediate hosts and as people have increased contact with infected water. Moreover, the number of children is increasing fastest in the developing regions of the world. Children and young adolescents are the age groups primarily responsible for the transmission of schistosomiasis. We are in an era when a predominantly young population will increasingly contaminate a finite environment.     

实施计划免疫对控制麻疹效果的分析

目的:探讨开展计划免疫对于控制麻疹流行的效果.方法:调查分析本地区实施计划免疫工作对于控制麻疹流行的效果,并总结计免工作经验.结果:实施计划免疫工作后,麻疹的发病率以及病死率均较实施前呈显著降低趋势,接种率以及接种后HI抗体阳性率均显著提高.结论:开展计划免疫工作能够提高麻疹疫苗接种率以及接种质量,有效控制麻疹的爆发流行.     

The dynamic epigenome and its implications in toxicology.

The epigenome serves as an interface between the dynamic environment and the inherited static genome. The epigenome is comprised of chromatin and a covalent modification of DNA by methylation. The epigenome is sculpted during development to shape the diversity of gene expression programs in the different cell types of the organism by a highly organized process. Epigenetic aberrations have similar consequences to genetic polymorphisms resulting in variations in gene function. Recent data suggest that the epigenome is dynamic and is therefore responsive to environmental signals not only during the critical periods in development but also later in life as well. It is postulated here that not only chemicals but also exposure to social behavior, such as maternal care, could affect the epigenome. It is proposed that exposures to different environmental agents could lead to interindividual phenotypic diversity as well as differential susceptibility to disease and behavioral pathologies. Interindividual differences in the epigenetic state could also affect susceptibility to xenobiotics. Although our current understanding of how epigenetic mechanisms impact on the toxic action of xenobiotics is very limited, it is anticipated that in the future, epigenetics will be incorporated in the assessment of the safety of chemicals.     

The effect of age on the pharmacokinetics of metoprolol and its metabolites.

1 Plasma concentrations of metoprolol and a pharmacologically active metabolite, H119/66, have been measured in young and elderly volunteers after a single dose of 100 mg metoprolol tartrate and after repeated administrated over a period of 1 week. Whilst concentrations of metoprolol are similar in each group, concentrations of H119/66 are approximately twice as high in the elderly. 2 Concentrations of unchanged metoprolol and of the major, but pharmacologically inactive, metabolite, H117/04, together with the two active metabolites of metoprolol have been determined in urine. Only the excretion of metoprolol was diminished in the elderly. 3 Areas under the plasma concentration curve for metoprolol after repeated administration are greater than would be predicted from single dose data, and possible explanations for this are discussed. Concentrations of the pharmacologically active metabolite, H119/66, remain unaltered during chronic dosing of metoprolol. 4 This study has shown that the effect of age on the pharmacokinetics of metoprolol and its metabolites is less pronounced than that observed for other drugs.     

The association between Internet addiction and both impulsivity and effortful control and its variation with age

Although the association of Internet addiction (IA) with self-regulation has been widely observed in previous studies, its variance with age remains poorly understood. Using dual models of self-regulation, we aimed to test the effects of effortful control and impulsivity on IA and to explore the effect of the interaction between age stage and self-regulation on IA. In this study, 4313 students nested in 100 classes were surveyed using the Internet Addiction Test (IAT), the Dual-Modes of Self-Control Scale (DMSC-S) and a demographic questionnaire. Hierarchical generalized linear models (HGLMs) were then used to test our assumptions. The results indicated that the IA prevalence rate among the surveyed adolescents was 10.9%, and IA was found to be negatively related to the effortful control trait and positively related to the impulsivity trait. Compared with primary school students, middle school students were more likely to be Internet addicts; however, the prevalence of IA among college students was comparable to that among middle school students. A slopes-as-outcome model showed that the association between IA and effort control was stronger among junior high school students than among students in other grade levels, but no grade differences were found in the slopes for impulsivity. We integrate our results with the findings of previous studies and discuss possible theoretical implications.     

The effects of age and sex on the disposition of acetylsalicylic acid and its metabolites.

The disposition of a low dose (600 mg) of acetylsalicylic acid (ASA) and its metabolites (salicylate, salicyluric acid and salicyl glucuronides) was studied in 25 male and female patients of different ages. Plasma levels of ASA and salicylate were found to be significantly higher in the females (young and elderly), whereas plasma levels of salicyluric acid were found to be significantly higher in the elderly (male and female) groups. The higher plasma levels of ASA and salicylate in the females appear to be due to an intrinsically lower metabolic activity in that sex, while the lower clearance of salicyluric acid leads to the accumulation of that compound in the aged. No age and sex effects were found to influence the volumes of distribution of ASA, salicylate and salicyluric acid.     

美国专利重复授权审查标准研究及对我国的启示

通过分析美国近期发生的“Lilly vs Teva”生物医药专利重复授权纠纷案,深入研究美国专利重复授权的审查标准,在此基础上讨论我国目前重复授权的审查标准,指出存在的问题及可能带来的一些不利影响。最后结合美国重复授权审查标准,对我国重复授权审查标准的完善提出建议。     

Influence of pH on amine toxicology and implications for harmful algal bloom ecology

In marine and estuarine conditions, pH-dependent aquatic toxicity associated with Prymnesium parvum has been previously demonstrated with greater toxicity observed at higher pH. Recent research by our group extended such observations to inland waters in Texas, USA. Because prymnesins (prymnesin-1, prymnesin-2) represent the only P. parvum toxins reported in the peer-reviewed literature, we hypothesized that P. parvum toxins may behave like weak bases in surface waters due to the presence of a primary amine. Employing a widely accepted computational model (ACD/Labs), we predicted physicochemical properties to support interpretation of experimental findings, specifically focusing on the amine-containing hydrophobic portion of these molecules. Using different computational models, alternative pK_a values for prymnesins have been proposed by others. Herein, additional examination of our proposed hypothesis identifies the importance of considering subtle changes in ionization state on the lipophilicity, bioavailability (e.g., log D, log D_lip−water, Bioconcentration factor), and aquatic toxicity of ionizable chemicals over an environmentally-relevant pH gradient. If prymnesins represent causative toxins released by P. parvum as previously reported or if new toxins are identified in the future, a closer evaluation of our findings further highlights the importance of considering site-specific pH during environmental assessment and management efforts for P. parvum in inland waters.     

The nootropic concept and its prospective implications

Giurgea, C.E. : The nootropic concept and its prospective implications. Drug. Dev. Res. 2:441–446, 1982. The nootropic concept emerged about 10 years ago essentially from the unusual pharmacology of piracetam, which later on was confirmed and extended to human pharmacoclinics and therapeutics. A nootropic drug is characterized by a direct functional activation of the higher integrative brain mechanisms that enhances cortical vigilance, a telencephalic functional selectivity, and a particular efficiency in restoring deficient higher nervous activity. In contradistinction to other psychotropic drugs, nootropics do not induce direct reticular, limbic, or other subcortical events. Little is known with regard to nootropic, neurochemical mechanisms of action except that they interact with factors that contribute to the neuronal membrane stability, and possibly with the brain 5-HT. Main therapeutical indications seem to be in children with speech disorders, in the posttraumatic, and posthypoxic sequelae, in vertigo of central origin, and in geriatric, moderately impaired, possibly dysmnesic patients. Other drugs, such as pyritinol, meclofenoxate, and, to some extent, hydergine and vincamine, do show partially nootropic activities. The nootropic line of research is by now multifaceted to deepen the neurochemical and neurophysiologic comprehension of nootropics' mode of action; to make clearer their clinical differential profile; to enlarge the nootropic framework to some other existing drugs, clinically if not pharmacologically related to piracetam; and to find new, more potent, and possibly more selective nootropic agents. The general aim of nootropic research is to find new drugs capable of enhancing directly the efficiency of the cognitive, noetic activity of the brain, thus compensating various neuro-psychologic deficits such as, but not exclusively, those related to aging.     

Clostridium difficile-associated disease: changing epidemiology and implications for management

Clostridium difficile-associated disease (CDAD) is increasingly being reported in many regions throughout the world. The reasons for this are unknown, are likely to be multifactorial, and are the subject of several current investigations. In addition to the upsurge in frequency of CDAD, an increased rate of relapse/recurrence, disease severity and refractoriness to traditional treatment have also been noted. Moreover, severe disease has been reported in non-traditional hosts (e.g. younger age, seemingly healthy, non-institutionalised individuals residing in the community, and some without apparent antimicrobial exposure). A previously uncommon and more virulent strain of C. difficile has been reported at the centre of multiple transcontinental outbreaks. The appearance of this more virulent strain, in association with certain environmental and antimicrobial exposure factors, may be combining to create the 'perfect storm'. It is human nature to be reactive; however, the successful control of C. difficile will require healthcare systems (including administrators, and leadership within several departments such as environmental services, infection control, infectious diseases, gastroenterology, surgery, microbiology and nursing), clinicians, long-term care and rehabilitation facilities, and patients themselves to be proactive in a collaborative effort. Guidelines for the management of CDAD were last published over a decade ago, with the next iteration due in the fall (autumn) of 2007. Several newer therapies are under investigation but it is unclear whether they will be superior to current treatment options.     

Physiological changes due to age. Pharmacodynamic changes of drug action and implications for therapy.

The elderly respond differently to drugs than do younger people. Their physiological response is much more variable, and predictability of drug action is much less certain. When all non-pharmacological factors and age-associated pharmacokinetics are taken into account, there is still no full explanation of the potentially altered drug action and increased drug toxicity observed in the elderly. It is only relatively recently that age-associated physiological changes (primary age changes), their interplay with age-associated pathophysiological changes (secondary age changes) and environmental changes (tertiary age changes) have been studied with regard to the effect of those changes on the pharmacodynamics of drug action. In general, age-associated pharmacodynamic changes, i.e. changes in the type, intensity and duration of drug action, have been associated with changes in receptor function (e.g. altered receptor number and affinity, altered second messenger function, altered cell response), changes in the homeostatic mechanisms, and reduced reserve capacity. It is important to realise that these changes, which can differ greatly among patients, may be responsible for an increased incidence of adverse drug reactions and therapeutic failure. They may also mandate a higher dose in some circumstances, as some organs become less responsive to drug action with age.