Repeated inhalation of crack-cocaine affects spermatogenesis in young and adult mice.

To investigate the effects of repeated crack-cocaine inhalation on spermatogenesis of pubertal and mature Balb/c mice, ten young (Y(ex)) and ten adult (A(ex)) Balb/c mice were exposed to the smoke from 5 g of crack with 57.7% of pure cocaine in an inhalation chamber, 5 days/week for 2 months. The young (Y(c)) and adult (A(c)) control animals (n = 10) were kept in a specially built and controlled animal house facility. The morphologic analysis of both testes of all animals included the analysis of quantitative and qualitative histologic parameters to assess the effect of crack-cocaine on spermatogenesis and Leydig cells. Apoptosis was determined by immunolabeling with caspase-3 antibodies. Compared to the Y(c) animals, Y(ex) animals showed a significant reduction in the number of stage VII tubules per testis (p = 0.02), Sertoli cells (p < 0.001) and elongated spermatids (p = 0.001). Comparisons between the Y(ex) and A(ex) groups identified a significant reduction in the number of Sertoli cells (p < 0.001) and round spermatids (p < 0.001) in the Y(ex) group and a significant increase in apoptotic Leydig cells (p = 0.04) in the A(ex) group. The experimental results indicate that crack-cocaine smoke inhalation induced spermatogenesis disruption in chronically exposed mice, particularly in pubertal mice.

Intrathecal baclofen pump exchange in multiple sclerosis. Factors affecting baclofen efficacy and dose adjustement. A case report. / Recambio de bomba intratecal en esclerosis múltiple. Factores que interfieren en la eficacia y ajuste de dosis de baclofeno. A propósito de un caso.

Multiple sclerosis is a neurological disease that presents with various symptoms; in some cases it is progressive and highly disabling, requiring invasive techniques to treat pain and spasticity. The use of intrathecal baclofen infusions is an effective and safe alternative for patients with severe and refractory spasticity. The therapy can improve quality of life, but must be performed in a pain unit by medical staff trained in the technique, its indications, pharmacology, and the potential risks of both the implant and the drug. The treatment can be individualized and patients must be followed up periodically.

SNPs from BCHE and DRD3 genes associated to cocaine abuse amongst violent individuals from Sao Paulo, Brazil.

Violence and drug abuse are highly destructive phenomena found world-wide, especially in Brazil. They seem to rise proportionally to one another and possibly related. Additionally, genetics may also play a role in drug abuse. This study has focused on identifying the use of cocaine within postmortem cases arriving at the Institute of Legal Medicine of Sao Paulo as well as the presence of certain single nucleotide polymorphisms (SNPs) to better understand one's susceptibility to abuse the drug. Both hair and blood samples have been extracted through a simple methanol overnight incubation or a rapid dilute-and-shoot method, respectively. The samples were then analyzed using an UPLC-ESI-MS/MS and genotyped through RT-PCR. Statistical analyses were performed via SPSS software. From 105 postmortem cases, 53% and 51% of the cases shown to be positive for cocaine in hair and blood, respectively. Genetic wise, a significant difference has been observed for SNP rs4263329 from the BCHE gene with higher frequencies of the genotypes A/G and G/G seen in cocaine users (OR=8.91; 95%CI=1.58-50.21; p=0.01). Likewise, also SNP rs6280 from the DRD3 gene presented a significant association, with both genotypes T/C and C/C being more frequent in users (OR=4.96; 95% CI=1.07-23.02; p=0.04). To conclude, a rather high proportion of cocaine has been found, which may suggest a connotation between the use of the drug and risky/violent behaviors. Additionally, significant associations were also found within two SNPs related to cocaine use, however, due to several inherent limitations, these must be confirmed.

Determination of cocaine and its derivatives in hair samples by liquid phase microextraction (LPME) and gas chromatography-mass spectrometry (GC-MS).

Hair testing is a recognized approach when it comes to accessing historical drug use. According to the World Drug Report of United Nations Office on Drugs and Crime (UNODC) 2015, Brazil is the largest cocaine (COC) market in South America. New analytical methodologies to detect crack/cocaine analytes in hair samples are highly desirable. Here, a method consisting of a liquid-phase microextraction (LPME) as a clean-up step, followed by gas chromatography-mass spectrometry (GC-MS) analysis has been proposed. The new validated method consisted of a washing step; an overnight incubation with methanol and a quick derivatization with butylchloroformate. Once derivatized, the samples were then submitted to the LPME procedure. Limits of detection (LoD) and quantitation (LoQ) obtained were of 0.1 and 0.5ng/mg for COC 0.4 and 0.5ng/mg for anhydroecgonine methyl ester (AEME); 0.03 and 0.05 for cocaethylene (CE), respectively and 0.05ng/mg for both LoD and LoQ for benzoylecgonine (BZE). All calibration curves were linear over the scope applied, from LoQ up to 20ng/mg, with a r2>0.99. Precision and accuracy assays showed acceptable %RSD values, according to international guidelines. Twelve postmortem head hair samples stemming from the Institute of Legal Medicine of Sao Paulo (IML-SP) have been analyzed, from which seven have shown to be positive for COC (0.75->20ng/mg) and BZE (0.1->20ng/mg). Apart from COC's main metabolite, four samples were also positive for CE (0.1-3.9ng/mg) and three samples for AEME (0.5-4.9ng/mg). To conclude, the LPME technique together with GC-MS analysis have shown promising results and were able to meet the demand of the laboratory of analyzing postmortem hair samples to look for all four analytes.

Amphetamine, cocaine and cannabinoids use among truck drivers on the roads in the State of Sao Paulo, Brazil.

Drugs are important risk factors for traffic accidents. In Brazil, truck drivers report using amphetamines to maintain their extensive work schedule and stay awake. These drugs can be obtained without prescription easily on Brazilian roads. The use of these stimulants can result in health problems and can be associated with traffic accidents. There are Brazilian studies that show that drivers use drugs. However, these studies are questionnaire-based and do not always reflect real-life situations. The purpose of this study was to demonstrate the prevalence of drug use by truck drivers on the roads of Sao Paulo State, Brazil, during 2009. Drivers of large trucks were randomly stopped by police officers on the interstate roads during morning hours. After being informed of the goals of the study, the drivers gave written informed consent before providing a urine sample. In addition, a questionnaire concerning sociodemographic characteristics and health information was administered. Urine samples were screened for amphetamines, cocaine, and cannabinoids by immunoassay and the confirmation was performed using gas chromatography-mass spectrometry (GC-MS). Of the 488 drivers stopped, 456 (93.4%) provided urine samples, and 9.3% of them (n=42) tested positive for drugs. Amphetamines were the most commonly found (n=26) drug, representing 61.9% of the positive samples. Ten cases tested positive for cocaine (23.8%), and five for cannabinoids (11.9%). All drivers were male with a mean age of 40 ± 10.8 years, and 29.3% of them reported some health problem (diabetes, high blood pressure and/or stress). A high incidence of truck drivers who tested positive for drug use was found, among other reported health problems. Thus, there is an evident need to promote a healthier lifestyle among professional drivers and a need for preventive measures aimed at controlling the use of drugs by truck drivers in Brazil.

Ayahuasca: uma revisão dos aspectos farmacológicos e toxicológicos / Ayahuasca: a review of pharmacological and toxicological aspects

A ayahuasca é uma bebida psicoativa originariamente utilizada em rituais de tribos indígenas da região amazônica. Esta bebida é preparada pela infusão de caules da Banisteriopsis caapi Morton, que contém Beta-carbolinas que são inibidoras da monoaminoxidase (MAO), e de folhas da Psychotria viridis Ruiz & Pavón, que contém o alucinógeno N,N-dimetiltriptamina (DMT). A enzima MAO degrada a DMT no fígado e intestino. No Brasil, a ayahuasca tem sido incorporada em rituais de grupos sincréticos religiosos e seu uso dentro do contexto religioso é amparado por lei federal. Atualmente, esses grupos têm se espalhado na Europa e Estados Unidos, chamando a atenção de pesquisadores internacionais quanto aos efeitos da ayahuasca. Estudos têm indicado que a ayahuasca poderia ter aplicações terapêuticas como no tratamento da farmacodependência e até sugerem seu uso seguro por adultos sadios. Entretanto, poucos estudos têm sido conduzidos para melhor avaliação de suas propriedades. O objetivo do artigo é mostrar uma revisão geral da história até as recentes descobertas envolvendo a farmacologia e a toxicologia da ayahuasca.

Ayahuasca (or caapi in Brazil) is a psychoactive plant beverage initially used by shamans in religious rituals practiced by indigenous peoples in the Amazon region. It is prepared by infusing the pounded stems of Banisteriopsis caapi Morton, a liana which contains beta-carbolines, alkaloids that are potent monoamine oxidase (MAO) inhibitors, together with the leaves of Psychotria viridis Ruiz & Pavón, which contains the psychedelic agent N,N-dimethyltryptamine (DMT). The enzyme MAO normally degrades DMT in the liver and gut. In Brazil, the use of ayahuasca within religious ceremonies is protected by law and it has been incorporated into rituals of syncretic religious groups. Some of these groups have established themselves in the United States and European countries, attracting international research interest in the effects of ayahuasca. Studies suggest that it may have therapeutic applications, such as in the treatment of drug addiction, and that it can be used safely by healthy adults. However, too few studies have been performed for a good assessment of its properties to be made. The aim of this article is to present a review of the history of ayahuasca, up to the recent discoveries concerning its pharmacology and toxicology.

Free-radical scavenging action of medicinal herbs from Ghana: Thonningia sanguinea on experimentally-induced liver injuries.

The antioxidant action of medicinal herbs used in Ghana for treating various ailments was evaluated in vitro and in vivo. Five plants, Desmodium adscendens, Indigofera arrecta, Trema occidentalis, Caparis erythrocarpus, and Thonningia sanguinea were tested for their free radical scavenging action by their interaction with 1,1-diphenyl-2-picrylhydrazyl (DPPH). Of these five plants, only Thonningia sanguinea was found to scavenge the DPPH radical. Lipid peroxidation in liver microsomes induced by H2O2 was also inhibited by T. sanguinea. The hepatoprotective effect of T. sanguinea was studied on acute hepatitis induced in rats by a single dose of galactosamine (GalN, 400 mg/kg, IP) and in mice by carbon tetrachloride (CCl4, 25 microl/kg, IP). GalN induced hepatotoxicity in rats as evidenced by an increase in alanine aminotransferase (ALT) and glutathione (GSH) S-transferase activities in serum was significantly inhibited when T. sanguinea extract (5 ml/kg, IP) was given to rats 12 hr and 1 hr before GalN treatment. The activity of liver microsomal GSH S-transferase, which is known to be activated by oxidative stress, was increased by the GaIN treatment and this increase was blocked by T. sanguinea pretreatment. Similarly, T. sanguinea pretreatment also inhibited CCl4-induced hepatotoxicity in mice. These data indicate that T. sanguinea is a potent antioxidant and can offer protection against GalN- or CCl4-induced hepatotoxicity.

Acetaminophen-derived activation of liver microsomal glutathione S-transferase of rats.

Effect of acetaminophen on glutathione (GSH) S-transferase and related drug metabolizing enzymes was studied in vivo. Rats were given acetaminophen (250 mg/kg, i.p.) 24 hr after the treatment with 3-methylcholanthrene (25 mg/kg, i.p.) and killed by decapitation at indicated times. Liver microsomal GSH S-transferase activity was increased to 331%, 193% and 158% of the control level at 3, 6 and 12 hr, respectively, after the administration of acetaminophen, while GSH content in the liver was markedly decreased at 3 and 6 hr. The increase in the transferase activity was not recovered by the treatment with dithiothreitol. Microsomal GSH peroxidase activity was significantly enhanced at 3 hr. Cytosolic GSH S-transferase and aniline hydroxylase in microsomes were gradually decreased with the increase in the time after administration of acetaminophen. Vmax values of both GSH S-transferase and GSH peroxidase activities in microsomes were increased at 3 hr. Two Km values were obtained for the peroxidase in the control, while only one was observed after the acetaminophen treatment. These results indicate that acetaminophen is converted via cytochrome P-450 to the reactive intermediate N-acetyl-p-benzoquinone imine, which binds to microsomal GSH S-transferase, resulting in the activation of the enzyme.

Screening of antioxidant action of various molds and protection of Monascus anka against experimentally induced liver injuries of rats.

Antioxidant action of various molds, which are traditionally used for the production of foods or alcoholic beverages in Japan, was studied in vitro and in vivo. Antioxidant action was evaluated by scavenging stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and lipid peroxidation of rat liver microsomes. Among 40 molds, 16 species showed the DPPH scavenging action, and the molds that can scavenge the DPPH radical inhibited lipid peroxidation. The mold with the strongest action, Monascus anka, was chosen for the investigation of a protective action against liver injury of rats. When galactosamine (GalN, 400 mg/kg) or GalN plus lipopolysaccharide (LPS, 0.5 microg/kg) was given intraperitoneally to rats (Sprague-Dawley), aspartate aminotransferase (AST) and glutathione (GSH) S-transferase (GST) activities in serum were significantly increased. However, such hepatotoxicities seen in the increase in serum enzyme levels were depressed when the extract prepared from M. anka was given 1 and 15 h before the toxic insultant. Liver microsomal GST activity, which is known to be activated by oxidative stress, was increased by GalN or GaIN plus LPS treatment and the increase was also inhibited by pretreatment with the extract. Pathomorphological changes in the liver caused by GalN treatment also were prevented by the mold extract. These results indicate that the extract of M. anka has radical scavenging action and ameliorates chemically induced hepatotoxicity.

Protective effect of the mold Monascus anka against acetaminophen-induced liver toxicity in rats.

Antioxidant and hepatoprotective actions of the mold Monascus anka (also called Beni-Koji in Japan) against acetaminophen (AAP)-induced liver toxicity were investigated. Serum aspartate aminotransferase and glutathione S-transferase (GST) activities increased by AAP (180 mg/kg, i.p.) treatment were depressed when the Beni-Koji preparation (4 ml/kg, i.p.) was given 15 and 1 hr before AAP administration. The decrease in liver cytosolic GST activity by AAP, reflecting the release of the enzyme into serum, was also blocked by the mold. Cytochrome P450 activity was inhibited by the Beni-Koji preparation. These results suggest that M. anka prevents AAP-induced liver toxicity by both antioxidant action and the inhibition of AAP metabolism.

Uso de esteróides andrógenos anabólicos por praticantes de atividade física das principais academias de Rechim e Passo Fundo/RS / Use of anabolic-androgenic steroids by sports practitioners attending the main gym centers in Erechim and Passo Fundo (Brazil)

Os esteróides andrógenos anabólicos (EAA) são substâncias quimicamente semelhantes à estosterona e que teriam a propriedade de aumentar a força e a massa muscular.Apesar de estarem associados a uma série deefeitos nocivos, principalmente sobre os sistemas cardiovascular, hepático e neuro-endócrino, verifica-se que o abuso de EAA tem aumentado consideravelmente nos últimos anos.No presente trabalho, o perfil dos praticantes de atividade física das academias de Erechim e Passo Fundo/RS e a incidência de uso de EAA foram verificados.Responderam aos questionários 418 praticantes de atividade física, de um total de 700 questionários distribuídos.A percentagem de uso foi de 6,5 por cento;todos usuários do sexo masculino, de uma população de 83 por cento de homens.O EAA mais utilizado foi o decanoato de nandrolona (35,29 por cento).Os EAA foram adquiridos em farmácias com receita médica (37,04 por cento).O perfil dos praticantes pode ser assim delineado: idade entre 21 e 25 anos, homens, estudantes universitários (62,67 por cento) e motivados por estética e ganho de força.Este estudo ressalta a necessidade de ações preventivas e educativas junto à população jovem.