Effects of Subchronic Manganese Chloride Exposure on Tambaqui (Colossoma macropomum) Tissues: Oxidative Stress and Antioxidant Defenses

This study aimed to evaluate oxidative stress parameters in juvenile tambaqui (Colossoma macropomum) exposed to 3.88 mg l^?1 Mn²⁺ for 96 hours. Biomarkers of oxidative stress, such as thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST) activities, as well as content of reduced glutathione (GSH), were analyzed in gill, liver, brain, and kidney. The presence of Mn²⁺ in the water corresponded to increased levels of Mn²⁺ accumulation according to the following sequence: gill > kidney > brain > liver. There was a significant increase in TBARS levels (40 %) and SOD activity (80 %) in addition to a significant decrease in GSH content (41 %) in gills of fish exposed to waterborne Mn²⁺. In hepatic tissue of the exposed animals, TBARS levels decreased significantly (35 %), whereas SOD (82 %) and GST activities (51 %) as well as GSH content (43 %) increased significantly. In brain of exposed juvenile fish, only significant decreases in SOD (32 %) and CAT activities (65 %) were observed. Moreover, the kidney of exposed fish showed a significant increase in TBARS levels (53 %) and a significant decrease in SOD activity (41 %) compared with the control. Thus, the changes in biomarkers of oxidative stress were different in the tissues, showing a specific toxicity of this metal to each organ.     

Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration

The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The gene that encodes human CYP2B6 is highly polymorphic, where the variation in brain enzyme levels could result in altered brain drug levels. CYP2B can metabolize nicotine, the main psychoactive ingredient in cigarettes; if altered brain CYP2B activity can influence nicotine brain levels, it could influence nicotine-mediated behaviors. To investigate this, a mechanism-based inhibitor selective for CYP2B, C8-xanthate (20 μg), was administered intracerebroventricularly (ICV) into the brain of rats, and 22 h later, nicotine levels were measured by in vivo microdialysis following nicotine (150 μg/kg intravenous). Brain nicotine levels from 15 to 30 min and the AUC_0–45min were both twofold higher (p<0.05) with C8-xanthate vs vehicle pretreatment; there was no difference in peripheral nicotine levels. Rats were then given ICV pretreatment with C8-xanthate/ASCF and underwent intravenous nicotine self-administration with 3.75–30 μg/kg per infusion dose. C8-xanthate pretreatment increased responding in progressive ratio (15 μg/kg per infusion dose, p<0.05). In a separate cohort, C8-xanthate increased the percentage of rats that acquired self-administration (7.5 μg/kg per infusion dose, p<0.05) from 40% after vehicle pretreatment to 100%, with no difference in peripheral nicotine levels measured at the end of behavior. In a third cohort, C8-xanthate increased the number of sessions required to meet extinction criteria (p<0.05). Together these data demonstrate that the brain CYP2B activity can influence nicotine brain levels and subsequent behaviors independent of hepatic metabolism. This suggests that human smokers with variable CYP2B brain levels could have different nicotine levels and reinforcement, which might have a role in smoking behaviors and dependence.     

PQLI Key Topics - Criticality, Design Space, and Control Strategy

This paper gives an overview of progress made by the ISPE PQLI initiative - a global industry-led initiative aimed at facilitating the implementation of ICH Q8, Q9, and ultimately Q10 guidance. Through this initiative ISPE is spearheading the effort to help industry begin to define areas where they will be able to provide the technical framework for the implementation of key elements of Quality by Design (QbD) - a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding based on sound science and quality risk management. Three topic areas, Design Space, Criticality, and Control Strategy were selected for specific focus and discussion, and this paper gives an overview of progress in these three areas.

Chronic Administration of Ketamine Elicits Antidepressant‐Like Effects in Rats without Affecting Hippocampal Brain‐Derived Neurotrophic Factor Protein Levels

Abstract: A growing body of evidence has pointed to the blockade of the N‐methyl‐d ‐aspartate (NMDA) receptor signaling as a potential therapeutic target for the treatment of major depression. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with ketamine and imipramine in rats. To this aim, rats were 14 days treated once a day with ketamine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open‐field tests. Ketamine and imipramine, at the all doses tested, reduced immobility time, and increased both climbing and swimming time of rats compared to the saline group, without affecting spontaneous locomotor activity. Brain‐derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine‐ and ketamine‐treated rats by ELISA sandwich assay. Chronic administration of both drugs, ketamine and imipramine, did not modify BDNF protein levels in the rat hippocampus. In conclusion, our findings demonstrate for the first time that chronic administration of acute inactive doses of ketamine (5 mg/kg) becomes active after chronic treatment, while no signs of tolerance to the behavioural effects of ketamine were observed after chronic administration of acute active doses (10 and 15 mg/kg). Finally, these findings further support the hypothesis that NMDA receptor could be a new pharmacological target for the treatment of mood disorders.     

Readability of Online Information on Celiac Disease: A Brief Report

Abstract

Celiac disease (CD) is an autoimmune condition characterized by an intolerance to dietary gluten for those with a genetic predisposition. The Internet has become a key source of information about CD as well as a gluten-free diet (GFD), although the quality is varied. There has been little investigation into the readability of online CD information. Keyword “celiac disease” was used for a search in the browser, Google Chrome. URLs of the first 100 English websites were recorded; sponsored or advertised websites were not included in the sample. Five recommended tests generated by Readable.io were utilized to assess the sample’s readability scores. Only one of the 100 websites received an acceptable reading score on two of the five reading assessments. Websites with extensions of .com or .org were equally likely to be written at the same unacceptable level. Informational websites on celiac disease may serve as an unintentional barrier for consumers seeking readable, online material on this health topic.     

Evaluation of a Community Health Worker Intervention to Reduce HIV/AIDS Stigma and Increase HIV Testing Among Underserved Latinos in the Southwestern U.S.

Objectives

Latinos are at an elevated risk for HIV infection. Continued HIV/AIDS stigma presents barriers to HIV testing and affects the quality of life of HIV-positive individuals, yet few interventions addressing HIV/AIDS stigma have been developed for Latinos.

Methods

An intervention led by community health workers (promotores de salud, or promotores) targeting underserved Latinos in three southwestern U.S. communities was developed to decrease HIV/AIDS stigma and increase HIV knowledge and perception of risk. The intervention was led by HIV-positive and HIV-affected (i.e., those who have, or have had, a close family member or friend with HIV/AIDS) promotores, who delivered interactive group-based educational sessions to groups of Latinos in Spanish and English. To decrease stigma and motivate behavioral and attitudinal change, the educational sessions emphasized positive Latino cultural values and community assets. The participant pool comprised 579 Latino adults recruited in El Paso, Texas (n=204); San Ysidro, California (n=175); and Los Angeles, California (n=200).

Results

From pretest to posttest, HIV/AIDS stigma scores decreased significantly (p<0.001). Significant increases were observed in HIV/AIDS knowledge (p<0.001), willingness to discuss HIV/AIDS with one''s sexual partner (p<0.001), and HIV risk perception (p=0.006). Willingness to test for HIV in the three months following the intervention did not increase. Women demonstrated a greater reduction in HIV/AIDS stigma scores when compared with their male counterparts, which may have been related to a greater increase in HIV/AIDS knowledge scores (p=0.016 and p=0.007, respectively).

Conclusion

Promotores interventions to reduce HIV/AIDS stigma and increase HIV-related knowledge, perception of risk, and willingness to discuss sexual risk with partners show promise in reaching underserved Latino communities.Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) has disproportionately affected U.S. Latinos during the last 25 years. Although Latinos constitute 16% of the U.S. population, they account for 19% of those living with HIV and 21% of new HIV infections.¹ Since 2006, the Centers for Disease Control and Prevention (CDC) has recommended HIV testing for all people aged 13–64 years.² However, nearly half (46%) of Latino adults aged 18–64 years have never been tested, compared with 23% of black and 50% of white adults.³ Additionally, HIV testing often occurs at a late stage among HIV-positive Latinos. More than one-third (36%) of HIV-positive Latinos were diagnosed with AIDS within one year of learning their HIV status, compared with 32% of white people and 31% of black people.³ Late HIV testing hinders treatment options and may contribute to unknowing HIV transmission.Factors contributing to low HIV testing rates among Latinos include poverty, lack of health-care access, and limited availability of culturally and linguistically responsive services.^1,4–6 HIV/AIDS stigma is another factor.^7,8 UNAIDS (Joint United Nations Programme on AIDS) defines HIV stigma as the “devaluation of people either living with or associated with HIV/AIDS.”⁹ Stigma often results from fears about HIV as well as the associations of HIV with stigmatized groups such as homosexuals, sex workers, and injection drug users.^9,10HIV/AIDS stigma has negative consequences both at a population level and for individuals who are its targets, including people living with HIV/AIDS. Stigmatizing attitudes toward people living with HIV/AIDS are associated with decreased HIV testing, limited utilization of HIV prevention services, and high-risk sexual behaviors.^7,10,11 Additionally, for people living with HIV/AIDS, the stigma associated with HIV/AIDS contributes to unwillingness to disclose HIV status, unsafe sexual behaviors, delays in care seeking, reduced treatment adherence, mental health issues, and difficulties obtaining social support.^9,11–14Despite significant implications, few interventions have been developed to reduce HIV/AIDS stigma.^10,11,15 Existing interventions have often focused on specific populations (e.g., university students and health-care providers), with few interventions focused on Latinos,^11,15,16 who have high levels of stigmatizing attitudes toward people living with HIV/AIDS^1,17,18 that contribute to negative outcomes.^7,19Among Latinos, research indicates that community health workers (promotores de salud, hereinafter “promotores”) are an effective and culturally acceptable means of reaching the population with health information and motivating health behaviors.^20,21 Promotores are well positioned to promote changes in their communities because they share language and cultural values, are held in high esteem, and are perceived as role models.²¹ Promotores have been used to address health conditions ranging from chronic diseases to preventive screenings.^20–22 Several interventions have incorporated promotores into HIV prevention, finding significant changes in HIV risk behaviors, HIV counseling and testing, and other psychosocial constructs important to prevention.^16,23–29 To date, few studies have used promotores in interventions to reduce HIV stigma among Latinos.¹⁶We describe and report findings of an intervention using promotores to reduce HIV/AIDS stigma and increase willingness to seek HIV testing among Latinos in three communities in the southwestern United States: Los Angeles, California; San Ysidro, California; and El Paso, Texas.     

Aluminum Content in Intravenous Solutions for Administration to Neonates

Background: Aluminum loading can reach toxic levels depending on the amount of aluminum intake in intravenous solutions (IV). Premature infants are at a higher risk of aluminum toxicity because of their reduced urinary aluminum elimination. All steps involved in the preparation of intravenous solutions for premature neonates in intensive care units were evaluated to determine to what degree, if any, they increased the aluminum load and should be considered when assessing the daily aluminum intake (<5 mcg/kg) established by the U.S. Food and Drug Administration (FDA). Methods: Products and medical devices used for the IV administration of solutions to preterm neonates were analyzed for their aluminum content. Commercial formulations, bags after compounding, and medications before and after their preparation, as well as infusion sets (including burettes) and syringes, were evaluated for their contribution to the aluminum levels in the final solution. The determination was carried out by atomic absorption spectrometry. Results: Currently available products used to prepare parenteral nutrition solutions as well as injectable medications usually administered to premature neonates present aluminum contamination. Bags, burettes, and syringes were also contaminated by aluminum to some degree, which may be leached during use. Conclusions: Commercial products are the main source of aluminum in parenteral nutrition; nevertheless, manipulation, containers, and administration sets increased aluminum levels by about 40%. Because this is a significant rate, these sources should be taken into account when calculating the amount of aluminum delivered to the patient in order to comply with FDA standards.     

Mediators of Positive Youth Development Intervention Change: Promoting Change in Positive and Problem Outcomes?

Advances in applied developmental science have contributed to the large literature on positive youth development (PYD) interventions. This study reports an investigation of a PYD program using an outcome-mediation evaluation model that drew on the treatment intervention science literature. The Changing Lives Program (CLP) is a community supported gender and ethnic inclusive PYD intervention framework. Using an empowerment approach, the CLP was implemented in a practice setting as a selective/indicated positive youth development program for multi-ethnic, multi-problem at risk youth in urban alternative high schools. The outcome-mediation evaluation model provided evidence in support of the direct outcome effects of the intervention. The model also proved effective in identifying at a micro process level a number of plausible causal mechanisms for use in the development of more conceptually complete models of the causal mechanisms that underlie intervention change. Implications for future development of theory informed empirically supported intervention models of PYD programs are discussed.     

Summary of invasive pneumococcal disease burden among children in the Asia-Pacific region

Invasive pneumococcal disease (IPD) burden is significant in the Asia-Pacific region. This review describes the epidemiology and Streptococcus pneumoniae (SP) serotype distribution of IPD in children in the Asia-Pacific region from studies published from 1999 to 2010. IPD incidence varies widely in Asia-Pacific countries depending on the method of surveillance, the population studied, and the time period. Incidences are highest for younger children, with rates near 100–200 cases per 100,000 children aged <1 or 2 years. Incidences of preventable disease are estimated to be 6–200 cases per 100,000. Heptavalent pneumococcal conjugate vaccine (PCV7) serotype coverage shows a very wide range over the Asia-Pacific region. Ten countries have high vaccine serotype coverage (>70%), and six countries have low vaccine serotype coverage (<50%). The majority of SP serotypes in children with IPD in most countries in the Asia-Pacific region are susceptible to penicillin (intermediate and resistant <50%); a few countries have SP serotypes with high level resistance to penicillin (intermediate and resistant >50%). Japan, Taiwan, and Thailand have high PCV7 serotype coverage. Countries with low pneumococcal resistance to antimicrobials have shown increasingly higher nonsusceptibility with time. National vaccination programmes that include PCV7, 10-valent pneumococcal conjugate vaccine (PCV), or 13-valent PCV would significantly affect IPD burden in children aged <5 years in the Asia-Pacific region, as well as the burden of penicillin-nonsusceptible IPD.     

A prospective study of Toxoplasma-positive pregnant women in southern Brazil: a health alert

We evaluated anti-Toxoplasma gondii IgM-reactive pregnant women seen at a high-risk pregnancy outpatient clinic. From March 2005 to January 2008 in Paraná, Brazil, pregnant women seen by the Brazilian Public Health System, in any gestational period, who were anti-T. gondii IgM-positive, were followed. Clinical symptoms were noted, and tests performed including IgA, IgG avidity, ultrasonogram, and amniocentesis (PCR/inoculation in mice). Of 75 patients, 8 showed low, 3 intermediate and 31 high IgG avidity. Of those who underwent the avidity test, 31 (70.5%) were in the second trimester of pregnancy. Thirty-two (42.7%) pregnant women received specific treatment. Six received triple combination treatment; in three, tachyzoites were isolated, although only one was PCR-positive, showing changes in the cerebral sonogram, borderline IgA, and the Sabin tetrad. One fetus died, and one non-reactive IgM pregnant woman showed ocular recurrence. The municipality of residence, contact with cats during adulthood, and ingestion of unpasteurized milk were shown to be important risk factors. Congenital toxoplasmosis was observed in a pregnancy referred late for treatment. Follow-up of children born to mothers with diagnosed or suspected acute toxoplasmosis is crucial in the management of the changes that toxoplasmosis may cause.