Metabolism of Biogenic Amines in Rat Brain during Pilocarpine-Induced Aggression

Quantitative distribution of bioactive substances in the brain of aggressive rats was studied. The norepinephrine/serotonin ratio increased in the temporal and parietal lobes, hypothalamus, and hippocampus of killer rats. The open filed behavior of aggressive rats is characterized by a long latency period, low locomotor activity, and slow movements. Exposure to constant darkness aggravated abnormal behavioral characteristics of aggressive rats. Serotonin content in the hypothalamus and visual cortex of these rats decreased by 75 and 76%, respectively.     

New predictors of outcome in idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis. New therapies have improved the outcome of this condition; accordingly, the factors that determine outcome may have changed. We aimed to identify determinants of survival in a cohort of consecutive patients with PAH: which was idiopathic, familial, or associated with anorexigen use. We performed a retrospective cohort study of 84 consecutive patients with PAH who underwent initial evaluation at our center from January 1994 to June 2002. The primary outcome was death or lung transplantation. Survival at 1, 3, and 5 [corrected] years was 87%, 75%, and 61%, respectively. Multivariate analysis showed that being of African-American or Asian descent was associated with an increased risk of death. Warfarin use was associated with a reduced risk of death. Higher serum albumin and cardiac index and acute vasoreactivity were independently associated with improved survival. These data suggest that the determinants of outcome have changed. Race is identified as a new risk factor, which may be attributable to biologic or socioeconomic differences. Cardiac function and acute reactivity of the pulmonary vascular bed remain strong independent predictors of outcome.     

Urban Health Indicator Tools of the Physical Environment: a Systematic Review

Urban health indicator (UHI) tools provide evidence about the health impacts of the physical urban environment which can be used in built environment policy and decision-making. Where UHI tools provide data at the neighborhood (and lower) scale they can provide valuable information about health inequalities and environmental deprivation. This review performs a census of UHI tools and explores their nature and characteristics (including how they represent, simplify or address complex systems) to increase understanding of their potential use by municipal built environment policy and decision-makers. We searched seven bibliographic databases, four key journals and six practitioner websites and conducted Google searches between January 27, 2016 and February 24, 2016 for UHI tools. We extracted data from primary studies and online indicator systems. We included 198 documents which identified 145 UHI tools comprising 8006 indicators, from which we developed a taxonomy. Our taxonomy classifies the significant diversity of UHI tools with respect to topic, spatial scale, format, scope and purpose. The proportions of UHI tools which measure data at the neighborhood and lower scale, and present data via interactive maps, have both increased over time. This is particularly relevant to built environment policy and decision-makers, reflects growing analytical capability and offers the potential for improved understanding of the complexity of influences on urban health (an aspect noted as a particular challenge by some indicator producers). The relation between urban health indicators and health impacts attributable to modifiable environmental characteristics is often indirect. Furthermore, the use of UHI tools in policy and decision-making appears to be limited, thus raising questions about the continued development of such tools by multiple organisations duplicating scarce resources. Further research is needed to understand the requirements of built environment policy and decision-makers, public health professionals and local communities regarding the form and presentation of indicators which support their varied objectives.     

Synthesis of polyureas by polycondensation of diamines with active derivatives of carbonic acid

New polycondensation reactions of active diphenyl carbonates and diphenyl carbamate with diamines were developed for the synthesis of high-molecular-weight polyureas. The kinetics and mechanism of carbonic acid active esters aminolysis model reactions were studied. Possible side reactions including nucleophilic substitution reaction were investigated as well. It is shown that novel methods advantageously distinguish from traditional methods of polyureas synthesis by low tendency to side reactions and facilitate the synthesis of linear polyureas and copolyureas. It is found that N,N′-bis(trimethylsilylated) diamines and salts of diamines as monomers can be successfully used in these reactions. Bioanalogous polymers promising for biomedical application — polyureas based on L -lysine — were synthesized using novel polycondensation reactions.     

Genetic and molecular factors in drug-induced liver injury: a review

The diagnosis of drug-induced liver injury (DILI) is challenging and based on complex diagnostic criteria. DILI falls into two main categories i) intrinsic "dose-dependent" Type A reactions ii) "idiosyncratic" or Type B reactions (which are usually not predictable). Idiosyncratic reactions can be immunoallergic (hypersensitivity), or metabolic, although overlap between categories can occur. The aim of this review is to summarise the general view of underlying mechanisms in DILI and to highlight individual risk factors for developing hepatotoxicity. Polymorphisms of bioactivation/toxification pathways through CYP450 enzymes (Phase I), detoxification reactions (Phase II) and excretion/transport (Phase III) are explored together with immunological factors that might determine DILI. The importance of establishing a multidisciplinary and multi-centric network to promote the understanding and research in hepatotoxicity is underlined. Challenges such as genetic analyses for association studies and whole genome studies, pharmacogenetic testing and future approaches to study DILI are considered. Knowledge regarding these operational mechanisms could provide further insight for the prospective identification of susceptible patients at risk of developing drug-induced hepatotoxicity.     

Analysis of IL-10, IL-4 and TNF-alpha polymorphisms in drug-induced liver injury (DILI) and its outcome

BACKGROUND/AIMS: The aim of this study was to assess whether genetic polymorphism of three important candidate cytokine genes, IL-10 (-1082G/A, -819C/T, and -592C/A), IL-4 (-590C/T) and TNF-alpha (-308G/A), play a role in the susceptibility to developing drug-induced liver injury (DILI), and in determining its phenotypic expression and severity. METHODS: Cytokine genotyping was analysed using TaqMan 5' allelic discrimination assay in 140 DILI patients (mean age 51 y, range 13-82, with equal sex distribution) included in the Spanish Registry and 268 healthy controls. RESULTS: Genotypes, haplotypes and allele frequencies were similar for both cases and controls. The low IL-10 producing haplotype was more prevalent in DILI patients with the absence of peripheral blood eosinophilia (Pc=0.004, OR=5.29, 95% CI: 2.04-13.67), revealing significantly lower median eosinophil counts (0.19 x 10(9)L; P<0.0002) compared to the intermediate (0.24 x 10(9)L) and high (0.40 x 10(9)L) IL-10 haplotypes. All cases with serious DILI outcome carried low or intermediate IL-10 producing haplotype and had normal or low eosinophil counts. CONCLUSIONS: IL-10, IL-4 and TNF-alpha genetic polymorphisms were not related to the risk of developing DILI. Low IL-10 producing haplotype is associated with low eosinophil count, absence of eosinophilia and may be associated with worse clinical outcome from DILI.     

Determinants of Risky Sexual Behavior Among Injecting Drug Users (IDUs) in Georgia

Injection risk practices and risky sexual behaviors place injection drug users (IDUs) and their sexual partners particularly vulnerable to HIV. The purpose of the study was to describe and understand determinants of high-risk sexual behavior among IDUs in Georgia. A cross-sectional, anonymous survey assessed knowledge, behavior and HIV status in IDUs in five Georgian cities (Tbilisi, Gori, Telavi, Zugdidi, Batumi) in 2009. The study enrolled in total 1,127 (1,112 males, 15 females) IDUs. Results indicate that occasional sexual relationships are common among male IDUs, including married ones. A subsample of 661 male IDUs who reported having occasional and paid sex partners during the last 12 months was analyzed. Multivariate analysis shows that not having a regular partner in the last 12 month (adjusted odds ratio (aOR) 1.57, 95 % CI 1.04 2.37), and using previously used needles/syringes at last injecting (aOR 2.37, 95 % I 1.10–5.11) are independent correlates of inconsistent condom use with occasional and paid sexual partners among IDUs. Buprenorphine injectors have lower odds of inconsistent condom use with occasional and paid sexual partners compared to heroin injectors (aOR 0.47, 95 % CI 0.27–0.80), and IDUs who live in Telavi are twice more likely to engage in such risky sexual behavior than capital city residents (aOR 2.55, 95 % CI 1.46–4.48). More effective programs focused on sexual risk behavior reduction strategies should be designed and implemented.