Exposure to mixed asymptomatic infections with Trypanosoma cruzi, Leishmania braziliensis and Leishmania chagasi in the human population of the greater Amazon

Lack of conservation of the Amazon tropical rainforest has imposed severe threats to its human population living in newly settled villages, resulting in outbreaks of some infectious diseases. We conducted a seroepidemiological survey of 1100 inhabitants of 15 villages of Paço do Lumiar County, Brazil. Thirty‐five (3%) individuals had been exposed to Trypanosoma cruzi (Tc), 41 (4%) to Leishmania braziliensis (Lb) and 50 (4.5%) to Leishmania chagasi (Lc) infections. Also, 35 cases had antibodies that were cross‐reactive against the heterologous kinetoplastid antigens. Amongst these, the Western blot assays revealed that 11 (1%) had Tc and Lb, that seven (0.6%) had Lc and Tc, and that 17 (1.6%) had Lb and Lc infections. All of these cases of exposures to mixed infections with Leishmania sp, and eight of 11 cases of Tc and Lb were confirmed by specific PCR assays and Southern hybridizations. Two cases had triple infections. We consider these asymptomatic cases showing phenotype and genotype markers consistent with mixed infections by two or more kinetoplastid flagellates a high risk factor for association with Psychodidae and Triatominae vectors blood feeding and transmitting these protozoa infections. This is the first publication showing human exposure to mixed asymptomatic kinetoplastid infections in the Amazon.     

An endocannabinoid mechanism in relapse to drug seeking: a review of animal studies and clinical perspectives

Detoxification from drug abuse is strongly threatened by the occurrence of renewed episodes of drug intake. In human addicts, relapse to drug seeking may take place even after a considerably long period from the last drug consumption. Over the last decade, the endocannabinoid system has received remarkable attention due to its unique features, including its rewarding properties closely resembling those of the most commonly abused substances and its multiple therapeutic implications. Although limited at present, evidence is now emerging on a possible participation of the endogenous cannabinoid system in the regulation of relapsing phenomena. Both stimulation and blockade of the central cannabinoid CB-sub1 receptor have proved to play an important role in drug- as well as in cue-induced reinstatement of drug seeking behavior. Indeed, while CB-sub1 receptor stimulation may elicit relapse not only to cannabinoid seeking but also to cocaine, heroin, alcohol and methamphetamine, this effect is significantly attenuated, when not fully prevented, by pretreatment with the CB-sub1 receptor antagonist rimonabant. However, corroborating data on the involvement of the cannabinoid system in stress-induced reinstatement are still rather scarce. The present review attempts to collect data obtained from different laboratories using diverse experimental approaches, to provide a comprehensive picture of the recent evidence of a relationship between the cannabinoid system and the neurobiological mechanisms leading to relapse. For each class of abused drugs, the conspicuous progress made in delineating the role of the endocannabinoid system in relapse to drug seeking has been examined by placing particular emphasis on the findings obtained from behavioral studies. After summarizing findings and implications emerging from the reviewed studies, we conclude by briefly discussing what information is still missing and how missing information might be obtained.     

Selective early cardiolipin peroxidation after traumatic brain injury: an oxidative lipidomics analysis

OBJECTIVE: Enhanced lipid peroxidation is well established in traumatic brain injury. However, its molecular targets, identity of peroxidized phospholipid species, and their signaling role have not been deciphered. METHODS: Using controlled cortical impact as a model of traumatic brain injury, we employed a newly developed oxidative lipidomics approach to qualitatively and quantitatively characterize the lipid peroxidation response. RESULTS: Electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry analysis of rat cortical mitochondrial/synaptosomal fractions demonstrated the presence of highly oxidizable molecular species containing C(22:6) fatty acid residues in all major classes of phospholipids. However, the pattern of phospholipid oxidation at 3 hours after injury displayed a nonrandom character independent of abundance of oxidizable species and included only one mitochondria-specific phospholipid, cardiolipin (CL). This selective CL peroxidation was followed at 24 hours by peroxidation of other phospholipids, most prominently phosphatidylserine, but also phosphatidylcholine and phosphatidylethanolamine. CL oxidation preceded appearance of biomarkers of apoptosis (caspase-3 activation, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positivity) and oxidative stress (loss of glutathione and ascorbate). INTERPRETATION: The temporal sequence combined with the recently demonstrated role of CL hydroperoxides (CL-OOH) in in vitro models of apoptosis suggest that CL-OOH may be both a key in vivo trigger of apoptotic cell death and a therapeutic target in experimental traumatic brain injury.     

Websites as a mode of delivering mental health information: perceptions from the Australian public

BACKGROUND: Many people with a mental disorder do not access help from mental health services. Internet websites may be a useful tool for disseminating mental health information to those who remain untreated, however little is known about people's perceptions of websites as mental health information sources. The current study examined characteristics that may influence belief in the helpfulness of websites as modes of delivering information about mental health. The study compared belief in the helpfulness websites to two traditional sources (bibliotherapy and health educators). METHODS: A total of 3,998 Australians aged 18 and above were surveyed. Logistic regression was used to explore the factors associated with rating a website, book and health educator as helpful sources of mental health information for a person described as having either depression, depression with suicidal thoughts, early schizophrenia or chronic schizophrenia. Factors investigated were demographics, exposure to mental illness, beliefs about dealing with mental illness alone, and personal and perceived stigmatising attitudes. RESULTS: Considerably more participants rated bibliotherapy and health educators as helpful in comparison to websites. Predictors of rating a website and book as helpful were identical; younger age, belief that it is helpful to deal with mental illness alone and being presented with depression and early schizophrenia vignettes in comparison to chronic schizophrenia. Predictors of rating a health educator as helpful were younger age, less personal stigma and being presented with a depression (without suicidal thoughts) vignette in comparison to chronic schizophrenia. CONCLUSIONS: These findings suggest the need for multiple modes of delivering mental health information. While many people feel that information delivered face-to-face is likely to be helpful, websites and other tools that maintain anonymity may be preferred by those who choose to or find themselves dealing with mental illness alone.     

Liver fibrosis in women with chronic hepatitis C: evidence for the negative role of the menopause and steatosis and the potential benefit of hormone replacement therapy

BACKGROUND AND AIMS: The rates of fibrosis progression in chronic hepatitis C are significantly different between males and females. The antifibrogenic effect of oestrogen has been proposed, possibly via inhibition of stellate cells. The aim of this study was to evaluate the severity of chronic hepatitis C in women, in relation to the menopause, steatosis and hormone replacement therapy (HRT). METHODS: From November 2003 to October 2004, women with chronic hepatitis C were enrolled prospectively. A questionnaire was completed prospectively and a blood sample was obtained on the day of biopsy. We identified characteristics associated with moderate/severe fibrosis using univariate and multivariate analysis. RESULTS: 251 women were included in the study. 122 women (52%) were menopausal and 65 were receiving HRT. 61 (24%) women with moderate/severe fibrosis (F2-F4, Metavir score) had a longer known duration of infection (>15 years), a higher body mass index and presented with steatosis more frequently than 190 (76%) women with mild fibrosis (F0-F1). Women with F2-F4 were more often menopausal (67% v 47%). The probability of fibrosis F2-F4 was lower for menopausal women receiving HRT (p = 0.012). Steatosis was more frequent and more severe in menopausal women. CONCLUSIONS: Severity of fibrosis was associated with a longer duration of infection (>15 years), a higher body mass index, advanced steatosis and the menopause. Menopausal women receiving HRT presented with a lower stage fibrosis. These results reinforce the hypothesis of a protective role of oestrogens in the progression of fibrosis. Steatosis may be implicated in the progression of fibrosis after the menopause.     

Metabolic effects of growth hormone (GH) replacement in children and adolescents with severe isolated GH deficiency due to a GHRH receptor mutation

BACKGROUND: The interpretation of the true effect of GH replacement therapy (GHRT) on metabolic status in GH deficiency (GHD) is often complicated by differing aetiologies of GHD and by the presence of additional hormone deficits. OBJECTIVE: To study the growth and response of the lipid profile and body composition to GHRT in a cohort of children with the same mutation in the GHRH receptor gene. Design Nine GH-deficient subjects (mean age 12.8 years, range 5-17.5 years; three male) in a rural community in Northeast Brazil were treated with GHRT for 2 years and compared with indigenous normal controls. MAIN OUTCOME MEASURES: Total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and body composition were measured at baseline and after 3, 12 and 24 months of GHRT. RESULTS: At baseline, the subjects with GHD had an adverse lipid profile, including elevated TC, elevated LDL-C and elevated TG. GHRT normalized TG in 3 months, LDL-C in 12 months and TC in 24 months. At baseline, older pubertal subjects with GHD had adverse body composition, including higher percentage fat mass (%FM), and GHRT induced a reduction in %FM that was maintained after 24 months. By contrast, younger prepubertal subjects did not have an adverse body composition. CONCLUSIONS: Lipid profile was abnormal at baseline, while abnormal body composition was only seen in older subjects in late puberty, indicating that body composition is less sensitive to the effect of GHD than lipid profile. GHRT improves lipid profile at all ages, while it affects body composition only towards the end of growth, emphasizing its importance in achieving normal somatic development in the transition period.     

Fatal disseminated toxoplasmosis during primary HIV infection

Toxoplasmosis is a well recognized manifestation of AIDS, but the disseminated disease is a rare condition and it has not been associated to HIV seroconversion to our knowledge. We describe a fatal episode of disseminated T. gondii acute infection with massive organ involvement during primary HIV infection. The serological data demonstrate primary T. gondii infection. The avidity index for HIV antibodies supports recent HIV-1 infection.     

Neuroimaging and APOE genotype: a systematic qualitative review

Apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer's disease (AD) and has also been implicated in cardiovascular disease, cognitive decline and cognitive changes in healthy ageing. The aim of this paper is to systematically review and critically assess the association between the APOE genotype and structural/functional cerebral changes as evidenced by brain imaging studies. A second aim is to determine whether these observed associations between APOE and the brain reflect changes which are consistent with the progression of AD neurodegenerative changes described in Braak stages. A search of Pubmed, Psycinfo, and Web of Science databases identified 64 articles available for qualitative review. The review found that presence of the APOE epsilon4 allele is associated with (1) hippocampal, amygdalar and entorhinal cortex atrophy, (2) increased brain atrophy, (3) increased white matter hyperintensity volumes and (4) altered cerebral blood flow and glucose metabolism patterns. It is possible that there are critical age ranges when these effects are evident and that the APOE epsilon2 genotype might present a risk. We conclude that structural brain change is associated with the APOE genotype and that it is more salient in younger ageing individuals.     

Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Greece

Mutations in β-glucocerebrosidase gene (GBA) have been implicated in Parkinson disease (PD). A Greek cohort of 172 PD patients and 132 control individuals were screened for GBA mutations by complete sequencing of the gene's exons. Four mutations previously associated with Gaucher disease and/or Parkinson's disease (L445P, D409H, E326K, H255Q) were detected, as well as five newly identified variants (R329H, L268L, S271G, T428K, V460L), providing for the first time data regarding the frequency of GBA mutations among PD patients and controls, in the Greek population. H255Q was the most common GBA mutation among Greek PD patients (4/172). V460L was only found in control individuals (2/132). Overall, GBA mutations were significantly overrepresented in a subgroup of early onset PD patients, compared to controls (P = 0.019, OR = 4.2; 95%CI = 1.28–13.82), suggesting that GBA mutations may modify age of onset for PD.