Modulation of neuroplasticity pathways and antidepressant-like behavioural responses following the short-term (3 and 7 days) administration of the 5-HT₄ receptor agonist RS67333

It has been recently suggested that activation of 5-HT? receptors might exert antidepressant-like effects in rats after 3 d treatment, suggesting a new strategy for developing faster-acting antidepressants. We studied the effects of 3 d and 7 d treatment with the 5-HT? receptor partial agonist RS67333 (1.5 mg/kg.d) in behavioural tests of chronic efficacy and on neuroplastic-associated changes, such as adult hippocampal neurogenesis, expression of CREB, BDNF, β-catenin, AKT and 5-HT? receptor functionality. RS67333 treatment up-regulated hippocampal cell proliferation, β-catenin expression and pCREB/CREB ratio after 3 d treatment. This short-term treatment also reduced immobility time in the forced swim test (FST), together with a partial reversion of the anhedonic-like state (sucrose consumption after chronic corticosterone). Administration of RS67333 for 7 d resulted in a higher increase in the rate of hippocampal cell proliferation, a significant desensitization of 5-HT? receptor-coupled adenylate cyclase activity and a more marked increase in the expression of neuroplasticity-related proteins (BDNF, CREB, AKT): these changes reached the same magnitude as those observed after 3 wk administration of classical antidepressants. Consistently, a positive behavioural response in the novelty suppressed feeding (NSF) test and a complete reversion of the anhedonic-like state (sucrose consumption) were also observed after 7 d treatment. These results support the antidepressant-like profile of RS67333 with a shorter onset of action and suggest that this time period of administration (3-7 d) could be a good approximation to experimentally predict the onset of action of this promising strategy.     

Photodynamic therapy of skin cancer: controlled drug delivery of 5-ALA and its esters

Photodynamic therapy (PDT) is a tool for the treatment of certain cancerous and pre-cancerous conditions in dermatology. 5-Aminolevulinic acid (5-ALA) and simple derivatives thereof are the principal compounds used for this purpose. For optimal efficacy, the drug must be released at an appropriate rate from the formulation and penetrate the skin, ideally to reach the target tissue at a sufficiently high concentration. Because ALA is a polar, zwitterionic compound, its formulation in conventional topical vehicles, and its inherently poor skin permeability, poses important challenges for the pharmaceutical scientist. The synthesis of more lipophilic (e.g. ester) prodrugs of ALA resolves, in part, these issues but then demands that questions, related to biotransformation back to the parent 5-ALA and to stability, be addressed. The objective of this review, therefore, is to evaluate the state-of-the-art and identify those areas in which additional research is necessary.     

Biomedical Properties of Propolis on Diverse Chronic Diseases and Its Potential Applications and Health Benefits

The use of alternative medicine products has increased tremendously in recent decades and it is estimated that approximately 80% of patients globally depend on them for some part of their primary health care. Propolis is a beekeeping product widely used in alternative medicine. It is a natural resinous product that bees collect from various plants and mix with beeswax and salivary enzymes and comprises a complex mixture of compounds. Various biomedical properties of propolis have been studied and reported in infectious and non-infectious diseases. However, the pharmacological activity and chemical composition of propolis is highly variable depending on its geographical origin, so it is important to describe and study the biomedical properties of propolis from different geographic regions. A number of chronic diseases, such as diabetes, obesity, and cancer, are the leading causes of global mortality, generating significant economic losses in many countries. In this review, we focus on compiling relevant information about propolis research related to diabetes, obesity, and cancer. The study of propolis could generate both new and accessible alternatives for the treatment of various diseases and will help to effectively evaluate the safety of its use.     

Role of Vitamin D in the Metabolic Syndrome

The prevalence of hypovitaminosis D has risen in developed countries over the past few years in association with lifestyle changes and an increase in unhealthy habits. Vitamin D deficiency has been implicated in various diseases, including metabolic syndrome (MetS), which is clinically defined by a set of metabolic and vascular disorders. The objective of this study was to review scientific evidence on the relationship between MetS and vitamin D deficiency to support the development of prevention strategies and health education programs. An inverse relationship has been reported between plasma vitamin D concentrations and the features that define MetS, i.e., elevated serum concentrations of glucose, total cholesterol, low-density lipoproteins, triglycerides, glycosylated hemoglobin, and a high body mass index. Numerous studies have described the benefits of vitamin D supplementation to improve outcomes in individuals with MetS. Interventions to maintain optimal vitamin D concentrations are proposed as a preventive strategy against MetS.     

Drinking and driving in southeastern Brazil: Results from a roadside survey study

Objective

The objective of this study is to present data from a roadside survey study on drinking and driving and alcohol consumption in southeastern Brazil.

Methods

A cross-sectional roadside survey study using a questionnaire and breathalyzer data is the method used to determine the prevalence of drinking and driving and to examine whether socio-demographic characteristics and drivers' behavior, attitude and alcohol consumption predicted positive blood alcohol content (BAC). The data were gathered from 2005 to 2007 through roadside surveys conducted on high volume public roads in four cities in southeastern Brazil. A total of 4182 randomly selected drivers took part in the research. Of these drivers, 3488 (83.4%) completed the questionnaire and agreed to take a breath test.

Results

Overall, 24.6% of drivers had a detectable blood alcohol concentration (BAC) and 15.9% had a BAC above the legal limit (0.6 g/l) at the time of the study. Logistic regression controlling for locale (city), sex, age and marital status was used to predict whether each driver would present a positive breath test. Socio-demographic characteristics, driving behaviors and attitudes, and alcohol consumption patterns were included as predictors. These analyses indicated that those who believed drinking and driving was a serious offense were about two-thirds as likely to have a positive breath test, and that drivers reporting a pattern of regular alcohol use were three times as likely to have a positive breath test.

Conclusions

These findings indicate that drinking and driving is relatively common in Brazil, and that it occurs considerably more frequently than similar surveys suggest, is the case in other countries.     

Extended use of a progesterone-releasing vaginal ring in nursing women: a phase II clinical trial

AIM: This study evaluates the performance of extended use of a progesterone (P)-releasing vaginal ring (PVR) in nursing women. METHOD: An open-label, noncomparative study on the safety and contraceptive efficacy of PVR replaced every 4 months of use (instead of 3 months) in 192 PVR acceptors. PVR use was initiated at day 59+/-2 (mean+/-SD) postpartum and continued until weaning or completing the use of three PVRs. RESULTS: Plasma P levels attained with the ring decreased from 17+/-1 to 14+/-1 nmol/L (mean+/-SE) from the third to the fourth month of use. These levels are still over the critical level of 10 nmol/L required for contraceptive protection. One pregnancy occurred in the third month of use of the second ring in 1998 woman-months of exposure. Extended use of the ring did not appear to affect breast-feeding performance or the rate of infant growth, and lactational amenorrhea was prolonged. No differences in the characteristics of bleeding between the third and fourth month of ring use were observed. CONCLUSION: The results indicate that use of the PVR for 4 months represents a safe and effective contraceptive for nursing women.     

Allergic reactions to beta-lactams

Allergy to beta-lactam antibiotics is the most frequent cause of drug-induced immunological reactions, although the prevalence is not exactly known. IgE- and T-cell-dependent responses are the main mechanisms involved, although other immunological mechanisms can also participate, especially in haematological abnormalities, such as immune haemolytic anaemia or thrombocytopoenia. Aside from their frequency, the clinical entities reported nowadays have changed little since penicillin was first used. The variation in beta-lactams consumption through the year has modified the pattern and specificities of allergic reactions for IgE and T cell responses. Benzylpenicillin is no longer the beta-lactams most frequently prescribed and other chemical structures, with new or modified haptens, have progressively replaced it. This is relevant for the diagnostic evaluation and management of beta-lactam hypersensitivity.     

Oleic Acid as Optimizer of the Skin Delivery of 5-Aminolevulinic Acid in Photodynamic Therapy

Purpose In photodynamic therapy (PDT), topically applied aminolevulinic acid (5-ALA) is converted to protoporphyrin IX (PpIX), which upon light excitation induces tumor destruction. To optimize 5-ALA-PDT via improving the highly hydrophilic 5-ALA limited penetration into the skin, we propose the use of the known skin penetration enhancer, oleic acid (OA). Methods In vitro skin penetration and retention of 5-ALA (1% w/w) were measured in the presence or absence of OA (2.5, 5.0, and 10.0% w/w) in propylene glycol (PG) using porcine ear skin as the membrane. In vivo accumulation of PpIX, 4 h after application, was determined fluorometrically in healthy mice skin by chemical extracton of skin samples. In vivo PpIX fluorescence kinetics was also investigated by noninvasive techniques using an optical fiber probe, for 30 min up to 24 h after topical application of 1.0% 5-ALA + 10.0% OA in PG on hairless mice skins. Results The flux and in vitro retention of 5-ALA in viable epidermis increased in the presence of 10.0% (w/w) OA. The amounts of PpIX, evaluated both by chemical tissue extractions and in vivo measurements by an optical fiber probe, increased after applying 5-ALA formulations containing 5.0 or 10.0% OA. Moreover, in vivo kinetic studies showed an increase in skin PpIX accumulation when formulations containing 10% OA were used; PpIX accumulation was also maintained longer compared to controls. Conclusions Both in vitro and in vivo results show the OA potential as an optimizer of 5-ALA skin delivery.     

Cerebral blood flow effects of acute intravenous heroin administration.

We examined acute effects of intravenous diacetylmorphine (heroin) administration - which induces a characteristic biphasic response: A short rush-sensation associated with intense pleasurable feelings followed by a subjectively different period of euphoria on cerebral blood flow. This was assessed in nine male heroin dependent patients participating in a heroin maintenance program in a setting resembling everyday pattern of heroin abuse. 99mTc-HMPAO was administered 45 s (rush) and 15 min (euphoria) after administration of i.v. heroin and 45 s after administration of saline (placebo). Plasma concentration of diacetylmorphine and its metabolites were measured with high-pressure liquid chromatography (HPLC). Compared to the euphoria condition, rush was associated with blood flow increase in the left posterior cerebellar lobe, left anterior cingulate gyrus and right precuneus. Our results are in line with recent reports indicating that the cerebellum is an important component in functional brain systems subserving sensory and motor integration, learning, modulation of affect, motivation and social behaviour, which all play important roles in reinforcing properties of opioids.     

Barriers and missed opportunities to HIV testing among injection drug users in two Mexico--US border cities

INTRODUCTION AND AIMS: Despite increasing HIV prevalence in cities along the Mexico--US border, HIV testing among high-risk populations remains low. We sought to identify barriers associated with HIV testing among injection drug users (IDUs) in Tijuana and Ciudad Juarez, the two largest Mexican border cities located across from San Diego, California and El Paso, Texas, respectively. DESIGN AND METHODS: In 2005, 222 IDUs in Tijuana and 205 IDUs in Ciudad Juarez were recruited by respondent-driven sampling and administered a questionnaire to collect socio-demographic, behavioural and HIV testing history data. Blood samples were provided for serological testing of HIV, hepatitis C virus (HCV) and syphilis. RESULTS: Only 38% and 30% of respondents in Tijuana and Ciudad Juarez, respectively, had ever had an HIV test. The factors independently associated with never having been tested for HIV differed between the two sites, except for lack of knowledge on HIV transmission, which was independently associated in both locales. Importantly, 65% of those who had never been tested for HIV in both cities experienced at least one missed opportunity for voluntary testing, including medical visits, drug treatment and spending time in jail. DISCUSSION AND CONCLUSIONS: Among this high-risk IDU population we found HIV testing to be low, with voluntary testing in public and private settings utilised inadequately. These findings underscore the need to expand voluntary HIV education and testing and to integrate it into services and locales frequented by IDUs in these Mexico--US border cities.