Cognitive changes in patient living with HIV-AIDS and apolipoprotein-E polymorphism: is there an association?

Patients with HIV-AIDS treated with antiretroviral drugs still have high prevalence of cognitive disorders and many factors are likely to contribute for ongoing neurologic decline such as chronic low-level infection, coinfections with hepatitis B and C and genetic influences, both the virus and the host. Some evidences suggest that the genetic APOE polymorphism may be an associated risk factor. This study aimed to evaluate the association between APOE polymorphisms and cognitive disorders in patients with HIV-AIDS. This was a cross-sectional study comprising 133 patients aged 19-59 years old, with HIV-AIDS and were assisted at the infectious disease outpatient clinics at Hospital Universitário Oswaldo Cruz, in Recife, Brazil. For cognitive evaluation, Mini-Mental State Examination test (MMSE) and Montreal Cognitive Assessment test (MoCA) were used. The determination of APOE gene polymorphism was performed by using the PCR-RFLP technique. Sociodemographic and clinical characteristics were not significantly associated to APOE ε4 polymorphism, except for the high results of CD4 rate (p < 0.015). There was an absence associated between APOE ε4 polymorphism and neurocognitive tests. This study found no association between cognitive alterations and APOE polymorphism in patients with HIV-AIDS in the Northeast of Brazil. The imbalance of APOE allelic frequency distribution, according to Hardy-Weinberg law, there could be an adjustment phase of its equilibrium suffered by the HIV virus, however, the mechanism is still unknown.

Chronic stress associated with hypercaloric diet changes the hippocampal BDNF levels in male Wistar rats.

Chronic stress, whether associated with obesity or not, leads to different neuroendocrine and psychological changes. Obesity or being overweight has become one of the most serious worldwide public health problems. Additionally, it is related to a substantial increase in daily energy intake, which results in substituting nutritionally adequate meals for snacks. This metabolic disorder can lead to morbidity, mortality, and reduced quality of life. On the other hand, brain-derived neurotrophic factor (BDNF) is widely expressed in all brain regions, particularly in the hypothalamus, where it has important effects on neuroprotection, synaptic plasticity, mammalian food intake-behavior, and energy metabolism. BDNF is involved in many activities modulated by the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, this study aims to evaluate the effect of obesity associated with chronic stress on the BDNF central levels of rats. Obesity was controlled by analyzing the animals' caloric intake and changes in body weight. As a stress parameter, we analyzed the relative adrenal gland weight. We found that exposure to chronic restraint stress during 12 weeks increases the adrenal gland weight, decreases the BDNF levels in the hippocampus and is associated with a decrease in the calorie and sucrose intake, characterizing anhedonia. These effects can be related stress, a phenomenon that induces depression-like behavior. On the other hand, the rats that received the hypercaloric diet had an increase in calorie intake and became obese, which was associated with a decrease in hypothalamus BDNF levels.

Suppression of T and B cell responses by Pterodon pubescens seeds ethanolic extract.

The anti-arthritic property of hydro alcoholic extract of Pterodon pubescens seeds was previously demonstrated using the Collagen Induced Arthritis (CIA) in mice, the most similar arthritis experimental model to human rheumatoid arthritis. This disease is characterized by chronic inflamed joints resulting from exacerbated functions of macrophages and T and B lymphocytes. Anti-inflammatory and antinociceptive activities by ethanolic extract of Pterodon pubescens seeds (EEPp) have been also reported. This study describes the effects of EEPp on T and B lymphocytes functions from healthy mice. Delayed Type Hypersensitivity (DTH), in vivo antibody production, T and B lymphocyte proliferation and NO production were determined. Mice treated orally for 7 days with EEPp had inhibited 58% of B cell antibody production (10(-3) mg kg(-1) b.wt.) and 33% of the DTH response (10(-4) mg kg(-1) b.wt.), also reducing tissue leukocyte infiltration. EEPp (10(-2) mg mL(-1)) also inhibited in vitro T (89%) and B (68%) lymphocytes proliferation and NO production (53%) by macrophage cell line J774. The immunosuppression here described for EEPp supports its potential therapeutic use to control exacerbated humoral and/or cellular immune response as in autoimmune and chronic inflammatory diseases.

Alcohol compliance monitoring and control with an ignition interlock

Objetivo: Este artículo describe losdispositivos y programas que utilizan alcolock o interlocky, brevemente, sus beneficios, limitaciones yproblemas en el control de conducir bajo los efectosdel alcohol. Se analiza la dimensión de este problemaen todo el mundo y se ofrece informaciónacerca del estado actual de los programas del alcolocken los países desarrollados.Material y métodos: Se hace un resumen de lasinvestigaciones publicadas sobre este tema. Se haceuna introducción a las normas de certificación. Sedescribe un programa de intervención motivacionalpara los usuarios del alcolock y, además, se señalanlas páginas de Internet donde se puede encontrarestos materiales para un programa deintervención motivacional en los idiomas inglés yespañol. Se hace un resumen de los datos conocidosacerca del alcolock como manera de predecir quéusuarios tendrán más posibilidades de reincidiruna convicción en el futuro en cuanto a conducirbajo los efectos del alcohol. Resultados: Los datos muestran que el alcolockes una manera efectiva de controlar la conducciónbajo el efecto del alcohol durante el tiempo queesté instalado, si bien el efecto no perdura muchotiempo después de que se retira. Los resultados obtenidosa partir de más de 7.000 infractores DWI(sancionados por conducir bajo la influencia delalcohol) en Canadá se utilizan para demostrarque los datos del alcolock son una herramientaútil para clasificar el riesgo de los conductores. Apesar de los potenciales beneficios del uso masivodel alcolock, sigue siendo poco utilizado por losjueces.Conclusiones: Las posibles consecuencias de laimplementación del alcolock son prometedoras,porque son relativamente baratas y ofrecen un métodotanto para predecir como para controlar a losconductores ebrios convictos (es decir, sancionadospor conducir bajo los efectos del alcohol y a los quegeneralmente se les retira el carné de circulación).Hasta que no haya más alcolocks en funcionamientono habrá reducciones sustanciales en los nivelesde conducción bajo el efecto del alcohol. Es por elloque es prematuro especular sobre el potencial efectoglobal del alcolock y su contribución a la seguridadvial

Objective: This paper describes alcoholignition interlock devices and programs and givesa summary overview of their benefits, limitationsand barriers in the control of alcoholimpaired driving. The extent of the worldwide alcoholimpaired driving problem is discussed alongwith some information about the current status ofignition interlock programs in developed nations.Material and methods: Published ignition interlockresearch studies are summarized in a table.Certification standards are introduced. An adjunctivemotivational counseling intervention for ignitioninterlock users is described and internet linksprovided to English and Spanish language counselingprogram materials. The uses of ignition interlockdata records is summarized as a means to predictwhich of the interlock users are more likely tohave future repeated alcohol driving convictions.Results: Evidence shows the alcohol interlock isan effective means of controlling alcohol impaireddriving during the time it is installed, but the effectdoes not endure for much time after the device isremoved. Evidence from over 7,000 DWI offendersin Canada is used to demonstrate that the interlockdata record is a useful tool for scaling driver risk.Despite the potential benefits of widespread interlockuse they are still underutilized by the courts.Conclusions: Ignition interlocks are promisingbecause they are relatively affordable and offer amethod of both prediction and control of convicteddrunk drivers. Until there are more interlockprograms operating there will not be substantialreductions in overall rates of impaired driving soit is premature to speculate about the full extentof their potential contribution to public road safety

Anti-arthritic effect and subacute toxicological evaluation of Baccharis genistelloides aqueous extract.

This work studies the potential subacute toxicological effects of the aqueous extract of Baccharis genistelloides (AEBg) and demonstrates a new anti-arthritic therapeutic effect. The treatment of the collagen-induced arthritis (CIA) group with 4.2 mg/kg AEBg induced an important decrease (75%) in CIA severity in all animals, while the 42 mg/kg dose treated only 50% of animals. After AEBg treatment, no significant differences were observed in body weight, aspect, color and relative weight of liver, kidneys, thymus or lungs between CIA groups. CIA and healthy AEBg groups treated with both doses did not show genotoxic effects to liver and kidney cells by the Comet assay, compared to its own control group. The augmented AST in the CIA group, compared to healthy control one was regularized by the AEBg treatment with 4.2 mg/kg but not with 42 mg/kg. No other significant difference was found on serum biochemical parameters, as well as on spontaneous or stimulated lymphocyte proliferation between CIA groups. The treatment of healthy animals with AEBg 4.2 mg/kg did not change the aspect, color or relative weight of kidneys, liver or lungs but reduced the body weight, the thymus and popliteal lymph node (PLN) relative weight and serum glucose and triglyceride levels. Concluding, our results indicate an anti-arthritic effects of AEBg without liver and kidney subacute toxicity and hypoglycemic and hypotriglyceridemic actions on healthy animals.

Alcohol ignition interlock programs.

The alcohol ignition interlock is an in-vehicle DWI control device that prevents a car from starting until the operator provides a breath alcohol concentration (BAC) test below a set level, usually .02% (20 mg/dl) to .04% (40 mg/dl). The first interlock program was begun as a pilot test in California 18 years ago; today all but a few US states, and Canadian provinces have interlock enabling legislation. Sweden has recently implemented a nationwide interlock program. Other nations of the European Union and as well as several Australian states are testing it on a small scale or through pilot research. This article describes the interlock device and reviews the development and current status of interlock programs including their public safety benefit and the public practice impediments to more widespread adoption of these DWI control devices. Included in this review are (1) a discussion of the technological breakthroughs and certification standards that gave rise to the design features of equipment that is in widespread use today; (2) a commentary on the growing level of adoption of interlocks by governments despite the judicial and legislative practices that prevent more widespread use of them; (3) a brief overview of the extant literature documenting a high degree of interlock efficacy while installed, and the rapid loss of their preventative effect on repeat DWI once they are removed from the vehicles; (4) a discussion of the representativeness of subjects in the current research studies; (5) a discussion of research innovations, including motivational intervention efforts that may extend the controlling effect of the interlock, and data mining research that has uncovered ways to use the stored interlock data record of BAC tests in order to predict high risk drivers; and (6) a discussion of communication barriers and conceptual rigidities that may be preventing the alcohol ignition interlock from taking a more prominent role in the arsenal of tools used to control DWI. Whether interlock programs can help public policymakers achieve their expressed goals of substantially reducing the level of impaired driving will remain uncertain until procedural barriers and intransigent judiciary practices can be overcome that provide for more systematic routine use of interlock programs. Despite strong effectiveness evidence in all studies to date, the real potential of this technology to reduce the road toll cannot be estimated until they are more widely adopted.

The impact of mandatory versus voluntary participation in the Alberta ignition interlock program.

Research has demonstrated that participation in an interlock program significantly reduces the likelihood of subsequent driving while intoxicated (DWI) convictions at least so long as the interlock device is installed in the vehicle. Despite the growing number of jurisdictions that allow interlock programs and the demonstrated success of these programs, the proportion of DWI offenders who actually have the device installed is minimal. In an effort to increase the proportion of offenders using interlocks, some jurisdictions require offenders to install an interlock as a condition of license reinstatement whereas others merely offer offenders a reduction in the period of hard suspension if they voluntarily participate in an interlock program. The objective of the present study was to determine the extent to which voluntary interlock participants are more or less successful in terms of subsequent recidivism than those for whom interlock program participation has been mandated. The issue was addressed using data from the interlock program in Alberta, Canada, which provides for both mandatory and voluntary participation. The recidivism experience of voluntary and mandatory interlock participants was examined both during and after the period of interlock installation. Cox regression revealed that, after controlling for (or equating) the number of prior DWI offenses, the survival rates of DWI offenders who were ordered to participate in the interlock program did not differ from those of voluntary participants. These results suggest that further use of mandatory interlock programs should be just as successful as voluntary programs when offenders share characteristics with those studied in Alberta.

The impact of mandatory versus voluntary participation in the Alberta ignition interlock program.

Research has demonstrated that participation in an interlock program significantly reduces the likelihood of subsequent driving while intoxicated (DWI) convictions at least so long as the interlock device is installed in the vehicle. Despite the growing number of jurisdictions that allow interlock programs and the demonstrated success of these programs, the proportion of DWI offenders who actually have the device installed is minimal. In an effort to increase the proportion of offenders using interlocks, some jurisdictions require offenders to install an interlock as a condition of license reinstatement whereas others merely offer offenders a reduction in the period of hard suspension if they voluntarily participate in an interlock program. The objective of the present study was to determine the extent to which voluntary interlock participants are more or less successful in terms of subsequent recidivism than those for whom interlock program participation has been mandated. The issue was addressed using data from the interlock program in Alberta, Canada, which provides for both mandatory and voluntary participation. The recidivism experience of voluntary and mandatory interlock participants was examined both during and after the period of interlock installation. Cox regression revealed that, after controlling for (or equating) the number of prior DWI offenses, the survival rates of DWI offenders who were ordered to participate in the interlock program did not differ from those of voluntary participants. These results suggest that further use of mandatory interlock programs should be just as successful as voluntary programs when offenders share characteristics with those studied in Alberta.

Subacute toxicity evaluation of a hydroalcoholic extract of Pterodon pubescens seeds in mice with collagen-induced arthritis.

When the immune system is stimulated there is a concomitant decrease in drug biotransformation and elimination that may results in unwanted drug response and toxic side effects. We investigated the subacute toxicity of a hydroalcoholic extract of Pterodon pubescens seeds (HEPp) to DBA1/J mice with collagen II-induced arthritis. The oral treatment with HEPp reduced the arthritic index without any concomitant alteration in their hematological examination, histopathological analysis and relative or absolute weight of several organs and in several clinical biochemical parameters when compared with the control group. We concluded that daily administration of anti-arthritic doses of HEPp did not induce any detectable subacute toxic side-effect in mice whose host defense mechanisms is active as we can observe in mice with CIA.

Predicting repeat DUI offenses with the alcohol interlock recorder.

The aim of this report has been to use information contained in the alcohol ignition interlock recorder to determine whether systematic analysis of it can be used to predict which DUI offenders will recidivate during the first 2 years after the interlock is removed. The interlock record was accumulated during a 4-year intervention study in Alberta, Canada. Data from more than 5.5 million breath tests collected during interlock use were analyzed retrospectively after allowing repeat DUI offenses to accumulate for up to 2 years post-interlock. The rate of interlock warns at low BAC (0.02-0.04%) and fails at higher BAC ( > 0.04%) were found to be predictive of later repeat DUI. The interlock record was used along with selected driver record variables and questionnaire data to identify predictor sets. CHAID segmentation analysis was used to identify combinations of predictor variables; these were joined with sensitivity analysis to compare different predictor combinations. Several variables, but primarily more prior DUIs and more interlock warns and fails logged during the first 5 months of interlock usage predict greater than 60% of repeat DUI with a false positive rate of less than 10%.

No evidence of association between the D10S1423 locus and Alzheimer disease in Brazilian patients.

In a genome survey for Alzheimer's disease (AD), Zubenko et al. (1998) reported that the 234bp allele of the D10S1423 locus was more frequent among AD cases than in controls. We have analyzed this polymorphic locus in patients and healthy controls and observed that the 226bp allele is the most frequent allele in the D10S1423 locus in Brazilian AD patients. However, no statistically significant association between any D10S1423 allele was observed in AD patients as well as in controls.

Classic Pick's disease type with ubiquitin-positive and tau-negative inclusions: case report.

We report on a patient presenting Pick's disease similar to the one reported by Pick in 1892, with ubiquitin-positive and tau-negative inclusions. His diagnosis was made on the basis of clinical (language disturbance and behavioural disorders), neuropsychological (progressive aphasia of the expression type and late mutism), neuroimaging with magnetic resonance (bilateral frontal and temporal lobes atrophy) and brain single photon emission computed tomography (frontal and temporal lobes hypoperfusion) studies. Macroscopic examination showed atrophy on the frontal and temporal lobes. The left hippocampus displayed a major circumscribed atrophy. The diagnostic confirmation was made by the neuropathological findings of the autopsy that showed neuronal loss with gliosis of the adjacent white matter and apearance of status spongiosus in the middle frontal and especially in the upper temporal lobes. There were also neuronal swelling (ballooned cell) and argyrophilic inclusions (Pick's bodies) in the left and right hippocampi. Anti-ubiquitin reaction tested positive and anti-tau tested negative.

Financial risk, plan types, and authorizations for managed alcohol treatment services.

OBJECTIVE: To estimate the effects of a managed behavioral healthcare organization's (MBHO's) products/plans and financial risk on levels and amount of care authorized for patients with alcohol-related problems. STUDY DESIGN: Secondary analysis of 1995-1998 MBHO authorization files. PATIENTS: Individuals diagnosed as having an alcohol-related problem without comorbidities. METHODS: Episodes (n = 10,872) were constructed with 60-day clear zones. Multinomial regression equations were used to analyze the proportional distribution of care authorized within episodes at 5 levels: inpatient, residential, partial hospitalization, intensive outpatient, and traditional outpatient. Care equivalency hours were calculated to combine data across outpatient sessions and inpatient days. A linear regression equation analyzed quantity of care within episodes. Product/plan types, financial risk, state of residence, and participation in the MBHO's network were explanatory variables. Age, sex, diagnosis, and episode number were control variables. RESULTS: Most utilization management care hours authorized are inpatient and residential. Relative to other products/plans for managing care, utilization management leads to 50% more authorized hours. More financial risk does not predict fewer care units authorized but shifts hospitalizations toward residential treatment. Increasing age and higher-severity diagnoses predict more overnight care authorizations. Pennsylvania, which mandates minimum levels of care and follows American Society of Addiction Medicine criteria, has significantly more care authorized compared with 8 other states with data. CONCLUSIONS: Other than in utilization management, MBHO financial risk does not predict less care authorization. The MBHO authorizes higher-level care for older adults, for those with more severe diagnoses, and for those with episodes of care beyond the second. Authorization data do not necessarily reflect utilization but can provide a useful, partial view of management strategies.

Evaluation of a program to motivate impaired driving offenders to install ignition interlocks.

Approximately 30,000 alcohol ignition interlocks, which prevent a drinking driver from operating a vehicle, are in use in the United States and Canada. Currently available studies indicate that interlocks reduce impaired driving recidivism while on the vehicle. However, in the United States, the practical effectiveness of these devices is limited because few offenders are willing to install them in order to drive legally. This paper reports on a study of a court policy that created a strong incentive for impaired driving offenders to install interlocks by making penalties (e.g., jail or electronically monitored house arrest) the alternative to the interlock. Comparison of the recidivism rates of offenders subject to this policy with offenders in similar, nearby courts not using interlocks indicated that the policy was producing substantial reductions in DUI recidivism.

Analysis of the disease risk locus DXS1047 polymorphism in Brazilian Alzheimer patients.

Alzheimer's disease (AD) is a disorder characterized by a progressive deterioration in memory and other cognitive functions. Four genes associated with early onset AD have been identified but familial AD is rare. The majority of late onset AD (LOAD) is caused by a complex inheritance with several genes interacting with environmental factors. The epsilon4 allele of the apolipoprotein E (APOE) gene has been reported worldwide as a risk factor associated with LOAD. The short variant of a polymorphism in the transcriptional region of the serotonin transporter gene (5-HTTLPR) was analyzed in several psychiatric conditions and found to be more frequently associated with European and Brazilian LOAD patients. Recently, allelic associations with LOAD were reported for five other loci, the most significant for one X-linked 202-bp allele, at the DXS1047 locus. We have analyzed this locus in Brazilian LOAD patients and observed that the 202-bp allele was not significantly more frequent among patients. In contrast, two other alleles (200 bp and 208 bp) were less frequent among AD male patients than in controls, confirming the importance of replicating association studies in different populations.

Amyotrophic lateral sclerosis with dementia. Case report.

A patient is described in whom a profound and rapidly progressive dementia occurred in association with clinical features of amyotrophic lateral sclerosis. A magnetic resonance imaging showed signs of frontal and especially left temporal atrophy. The pattern of dementia indicated impaired frontotemporal lobe functions, evidenced by reduced tracer uptake in the frontotemporal lobes on brain single photon emission computed tomography. Neuropathological examination in this patient revealed mild frontotemporal atrophy with spongiform changes and neuronal loss affecting mainly layers II and III of the frontotemporal cortices. There was atrophy of the hypoglossal nuclei. The spinal cord changes were consistent with motor neuron disease. The patient showed an irreversible and progressive course. A review of the relevant literature was made.

The Alberta Interlock Program: the evaluation of a province-wide program on DUI recidivism.

AIMS: This study was designed to determine the efficacy of alcohol safety interlocks in reducing recidivism among first and second driving-under-the-influence (DUI) offenders. It also evaluates the overall effectiveness of interlock programs where typically only a small portion of DUI offenders elect to install interlocks. DESIGN: The driving records of DUI offenders participating in interlock programs for 6 months for first offenders and 2 years for second offenders were compared with similar offenders who chose not to participate. SETTING: A province-wide program in Alberta, Canada. PARTICIPANTS: Records of 35,132 drivers convicted of DUI between 1 July 1998 and 30 September 1996 were analyzed MEASUREMENTS: Repeat DUI offenses during and after the interlock period. FINDINGS: While the offenders had interlocks on their vehicles, DUI recidivism was substantially reduced. Once the interlock had been removed and the participants had been reinstated, their DUI rate was the same as other offenders indicating that the interlock reduced recidivism while in place. Because only 8.9% of eligible drivers elected to participate in the interlock program, the program did not significantly increase the overall effectiveness of the province's management of DUI offenders. CONCLUSIONS: Interlocks are associated with a major reduction in DUI recidivism while on the vehicle of the offender. However, because few offenders elect to participate, the program produces only a small (5.9%) overall reduction in the recidivism rate of all DUI offenders.

Behavioral monitoring of DUI offenders with the Alcohol Ignition Interlock Recorder.

AIMS: To evaluate patterns of blood alcohol concentration (BAC) and driving logged on the ignition interlock recorder and to assess whether this event record is a useful outcome measure for a behavioral intervention. DESIGN: Descriptive analyses of recorder data and multivariate analysis of the predictors of high BACs associated with a motivational intervention for driving-under-the-influence (DUI) offenders using an interlock. SETTING: Two interlock service centers in Alberta, Canada. PARTICIPANTS: 1309 first-time and multiple DUI offenders who agreed to participate during interlock installation. INTERVENTION: A human-services (supportive guidance) intervention based on motivational interviewing and pragmatic counseling was delivered to interlock users in Calgary, but not to interlock users in Edmonton, Canada. MEASUREMENTS: This report summarizes the patterns and predictors of BAC warnings (0.02-0.039%) (20-39 mg/dl) and failures (> or = 0.04) (> or = 40 mg/dl) from more than 3 million in-vehicle breath tests. Data come from three sources: driver records, questionnaires and the interlock. FINDINGS: From the beginning to the end of the interlock use period, there was a significant linear decline in the proportion of positive BAC driving to total driving. After controlling for prior offenses, demographics and reported drinking levels, offenders in the intervention site (Calgary) were less likely to have recorded fail BACs than were offenders in the control site (Edmonton). The temporal patterns of BAC fails with the interlock mimic the high-risk periods for DUI arrests and alcohol-involved fatal crashes. CONCLUSIONS: The interlock successfully blocks drinking and driving during high-risk periods. Preliminary recorder data suggest the services intervention may be affecting DUI behavior.

The short variant of the polymorphism within the promoter region of the serotonin transporter gene is a risk factor for late onset Alzheimer's disease.

We analyzed a deletion/insertion polymorphism within the promoter region of the serotonin transporter gene (5-HTTPLR) in 81 patients with late onset Alzheimer's (AD) disease (mean age 70.02 +/- 8.13 years). Control groups included 81 normal subjects with comparable age (mean age 75.6 +/- 10.2) and 82 younger normal subjects (mean age 37.4 +/- 9.1). Statistical analysis showed a significant difference in the genotype and gene frequencies between the AD group and normal controls (chi 2 = 9.021; 2 d.f. and chi 2 = 5.59, 1 d.f., respectively, P < 0.05) due to the higher frequency of the L allele and the lower frequency of the s allele in controls than among AD patients. However, no differences were found in the genotype frequencies in older as compared to younger normal control groups (chi 2 = 0.337, 2 d.f. and P > 0.05). The present study confirms, in a different population, that the short variant of the 5-HTTPLR polymorphism may be a risk factor for late onset AD.