Heroin-assisted treatment as a response to the public health problem of opiate dependence

Injection drug use (involving the injection of illicit opiates) poses serious public health problems in many countries. Research has indicated that injection drug users are at higher risk for morbidity in the form of HIV/AIDS and Hepatitis B and C, and drug-related mortality, as well as increased criminal activity. Methadone maintenance treatment is the most prominent form of pharmacotherapy treatment for illicit opiate dependence in several countries, and its application varies internationally with respect to treatment regulations and delivery modes. In order to effectively treat those patients who have previously been resistant to methadone maintenance treatment, several countries have been studying and/or considering heroin-assisted treatment as a complementary form of opiate pharmacotherapy treatment. This paper provides an overview of the prevalence of injection drug use and the opiate dependence problem internationally, the current opiate dependence treatment landscape in several countries, and the status of ongoing or planned heroin-assisted treatment trials in Australia, Canada and certain European countries.

pH dependence of the progression in NMR T-2 relaxation times in post-mortem muscle

Continuous NMR T-2 relaxation measurements were carried out on seven rabbit longissimus muscle samples in the period from 25 min to 28 h post-mortem at 200 MHz for H-1. To display differences in post-mortern pH progress and extent of changes in water characteristics during conversion of muscle to meat, three of the seven animals were pre-slaughter injected with adrenaline (0.5 mg/kg live weight 4 h before sacrifice) to differentiate muscle glycogen stores at the time of slaughter. Distributed analysis of T-2 data displayed clear differences in the characteristics of the various transverse relaxation components dependent on progress in pH, as did the water-holding capacity of samples 24 h postmortem. This reveals a pronounced effect of the progressive change in pH on the subsequent development in physical/chemical states of water during the conversion of muscle to meat. Finally, the relaxation characteristics are discussed in relation to supposed post-mortem processes of protein denaturation.

Stereochemistry of cyclopentane derivatives from (2,3)J(CH) dependence on dihedral angle (theta H-C-C-X)

The (2,3)J(CH) dependence on dihedral angle (theta H-C-C-X) for cyclopentane derivatives was investigated. We observed that the combined use of experimentally obtained (2,3)J(CH) values and the theoretically determined dihedral angles between the corresponding nuclei can be used to infer the relative stereochemistry of the ring substituents in cyclopentane derivatives. There is a good correlation between the magnitude of (3)J(CH) and the dihedral angle between the hydrogen and the coupled carbon (R-2 = 0.88). Copyright (C) 2008 John Wiley & Sons, Ltd.

Methadone maintenance therapy for opioid dependence - A guide to appropriate use

Opioid dependence is a chronic, relapsing condition that is associated with significant morbidity and mortality. Methadone maintenance therapy involves the provision of a controlled supply of an orally administered opioid, thereby stabilising the opioid-dependent patient. Research studies have shown that methadone maintenance reduces illicit opioid use, opioid-related crime, premature mortality and the risk of HIV infection. It is most effective when prescribed at an adequate dosage (usually 60 to 100 mg/day) and when long term maintenance on methadone is the goal of treatment rather than detoxification from all drugs including methadone. Successful long term methadone maintenance is more likely when it takes place within the context of a well established therapeutic relationship and when the medical, social and psychological needs of patients are met either through direct assistance or referral.

Direct measurement of pulse distortion near the zero-dispersion wavelength in an optical fiber by frequency-resolved optical gating

The technique of frequency-resolved optical gating is used to characterize the intensity and the phase of picosecond pulses after propagation through 700 m of fiber at close to the zero-dispersion wavelength. Using the frequency-resolved optical gating technique, we directly measure the severe temporal distortion resulting from the interplay between self-phase modulation and higher-order dispersion in this regime. The measured intensity and phase of the pulses after propagation are found to be in good agreement with the predictions of numerical simulations with the nonlinear Schrodinger equation. (C) 1997 Optical Society of America.

Concentration dependence of sodium permeation and sodium ion interactions in the cyclic AMP-gated channels of mammalian olfactory receptor neurons

The dependence of currents through the cyclic nucleotide-gated (CNG) channels of mammalian olfactory receptor neurons (ORNs) on the concentration of NaCl was studied in excised inside-out patches from their dendritic knobs using the patch-clamp technique. With a saturating concentration (100 mu M) of adenosine 3', 5'-cyclic monophosphate (cAMP), the changes in the reversal potential of macroscopic currents were studied at NaCl concentrations from 25 to 300 mM. In symmetrical NaCl solutions without the addition of divalent cations, the current-voltage relations were almost linear, reversing close to O mV. When the external NaCl concentration was maintained at 150 mM and the internal concentrations were varied, the reversal potentials of the cAMP-activated currents closely followed the Na+ equilibrium potential indicating that P-Cl/P-Na approximate to 0. However, at low external NaCl concentrations (less than or equal to 100 mM) there was some significant chloride permeability. Our results further indicated that Na+ currents through these channels: (i) did not obey the independence principle; (ii) showed saturation kinetics with K(m)s in the range of 100-150 mM and (iii) displayed a lack of voltage dependence of conductance in asymmetric solutions that suggested that ion-binding sites were situated midway along the channel. Together, these characteristics indicate that the permeation properties of the olfactory CNG channels are significantly different from those of photoreceptor CNG channels.

Simultaneous two-wavelength holographic interferometry in a superorbital expansion tube facility

A new variation of holographic interferometry has been utilized to perform simultaneous two-wavelength measurements, allowing quantitative analysis of the heavy particle and electron densities in a superorbital facility. An air test gas accelerated to 12 km/s was passed over a cylindrical model, simulating reentry conditions encountered by a space vehicle on a superorbital mission. Laser beams with two different wavelengths have been overlapped, passed through the test section, and simultaneously recorded on a single holographic plate. Reconstruction of the hologram generated two separate interferograms at different. angles from which the quantitative measurements were made. With this technique, a peak electron concentration of (5.5 +/- 0.5) x 10(23) m(-3) was found behind a bow shock on a cylinder. (C) 1997 Optical Society of America.

The role of alcoholic beverage preference in the severity of alcohol dependence and adherence to the treatment

The severity of dependence on alcohol and the efficacy of diverse types of treatments for alcoholism have been the subject of various researches. This study focused on the types of beverages preferentially consumed by alcohol-dependent outpatients and their effects on the severity of dependence and therapeutic outcomes. Our sample comprised 153 patients, 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence, who were randomly divided into three different groups to receive topiramate (up to 300 mg/day), naltrexone (50 mg/day), or placebo during 12 weeks of follow-up. Spirits and beer were the main beverages consumed. At the start of this research, the group of spirits drinkers showed higher severity of alcohol dependence, higher craving for alcohol, more frequent history of treatments for alcoholism, and lower income than the group of beer preference drinkers. During the study, beer preference drinkers demonstrated higher adherence to the treatment, independently of the types of medications prescribed (P = .02, odds ratio, 2.46, 95% confidence interval, 1.17-5.19). This study suggests that the severity of dependence and the adherence to the treatment can be factors that set apart beer drinkers from spirits drinkers. As the compliance with the treatment for alcoholism was lower among spirits preference drinkers, a more intensive model of treatment would be necessary. (C) 2009 Elsevier Inc. All rights reserved.

Comparing topiramate with naltrexone in the treatment of alcohol dependence

To compare the efficacy of topiramate with naltrexone in the treatment of alcohol dependence. The investigation was a double-blind, placebo-controlled, 12-week study carried out at the University of Sao Paulo, Brazil. A total of 155 patients, 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence. After a 1-week detoxification period, patients were assigned randomly to receive topiramate (induction to 300 mg/day), naltrexone (50 mg/day) or placebo. Time to first relapse (consumption of > 60 g ethyl alcohol), cumulative abstinence duration and weeks of heavy drinking. In intention-to-treat analyses, topiramate was statistically superior to placebo on a number of measures including time to first relapse (7.8 versus 5.0 weeks), cumulative abstinence duration (8.2 versus 5.6 weeks), weeks of heavy drinking (3.4 versus 5.9) and percentage of subjects abstinent at 4 weeks (67.3 versus 42.6) and 8 weeks (61.5 versus 31.5), but not 12 weeks (46.2 versus 27.8). Results remained significant after controlling for Alcoholics Anonymous attendance, which was higher in topiramate than in other groups. There were no significant differences between naltrexone versus placebo or naltrexone versus topiramate groups, but naltrexone showed trends toward inferior outcomes when compared to topiramate. The results of this study support the efficacy of topiramate in the relapse prevention of alcoholism. Suggestive evidence was also obtained for superiority of topiramate versus naltrexone, but this needs to be verified in future research with larger sample sizes.

Balance between early life tolerance and sensitization in allergy: dependence on the timing and intensity of prenatal and postnatal allergen exposure of the mother

P>Allergens can be maternally transferred to the fetus or neonate, though it is uncertain how this initial allergen exposure may impact the development of allergy responses. To evaluate the roles of timing and level of maternal allergen exposure in the early life sensitization of progeny, female BALB/c mice were given ovalbumin (OVA) orally during pregnancy, lactation or weekly at each stage to investigate the immunoglobulin E (IgE) antibody production and cellular responsiveness of their offspring. Exposure to OVA during pregnancy was also evaluated in OVA-specific T-cell receptor (TCR) transgenic (DO11.10) mice. The effect of prenatal antigen exposure on offspring sensitization was dependent on antigen intake, with low-dose OVA inducing tolerance followed by neonatal immunization that was sustained even when pups were immunized when 3 weeks old. These offspring received high levels of transforming growth factor-beta via breastfeeding. High-dose exposure during the first week of pregnancy or perinatal period induced transient inhibition of IgE production following neonatal immunization; although for later immunization IgE production was enhanced in these offspring. Postnatal maternal antigen exposure provided OVA transference via breastfeeding, which consequently induced increased offspring susceptibility to IgE antibody production according to week post-birth. The effect of low-dose maternal exposure during pregnancy was further evaluated using OVA transgenic TCR dams as a model. These progeny presented pronounced entry of CD4(+) T cells into the S phase of the cell cycle with a skewed T helper type 2 response early in life, revealing the occurrence of allergen priming in utero. The balance between tolerance and sensitization depended on the amount and timing of maternal allergen intake during pregnancy.

Ethical issues in neuroscience research on substance dependence treatment and prevention

Previous chapters have presented the latest findings in neuroscience research, and have pointed to potential treatment and prevention strategies. However, there are many ethical implications of the research itself, as well as the treatment and prevention strategies, that must be considered. The rapid pace of change in the field of neuroscience brings with it a host of new ethical issues, which need to be addressed. This chapter considers the important ethical and human rights issues that are raised by neuroscience research on psychoactive substance dependence.

Psychometric qualities of the Brazilian versions of the Fagerstrom Test for Nicotine Dependence and the Heaviness of Smoking Index

This study examined the psychometric properties of the Brazilian versions of the Fagerstrom Test for Nicotine Dependence (FTND) and the Heaviness of Smoking Index (HSI). The test-retest reliability of the FTND was assessed in a sample of 61 smoking university students, with a 15-day interval between assessments. The interrater reliability was examined in 30 smoking patients of a psychosocial care center for alcohol and drug users (PCC-AD). The reliability coefficient was estimated by the kappa and intraclass correlation coefficients. The predictive validity, internal consistency, and factor structure of the FTND and the HSI were evaluated by factor analysis in 271 smokers treated at an emergency unit and at the PCC-AD. The gold standard was the nicotine dependence criteria of DSM-IV, as assessed by the Structured Clinical Interview for DSM-IV. The FTND showed high reliability, with correlation coefficients of .92 for test-retest reliability and .99 for interrater reliability. Both the FTND and the HSI presented high levels of sensitivity and specificity. The internal consistency evaluation yielded a Cronbach`s alpha coefficient of .83 for the FTND and of .56 for the HSI. An exploratory factor analysis found 2 factors in the FTND, which were validated by a confirmatory factor analysis. The results obtained in this study confirm the validity and reliability of the Brazilian versions of the FTND and the HSI.