Regulation of Drug Transporters in the Testis by Environmental Toxicant Cadmium, Steroids and Cytokines.
Regulation of drug transporters in the testis by environmental toxicant cadmium, steroids and cytokines.
Filed under: Drug and Alcohol Rehabilitation
Spermatogenesis. 2012 Oct 1; 2(4): 285-293
Su L, Mruk DD, Cheng CY
The blood-testis barrier (BTB) provides an efficient barrier to restrict paracellular and transcellular transport of substances, such as toxicants and drugs, limiting their entry to the testis to cause injury. This is achieved by the coordinated actions of efflux and influx transporters at the BTB, which are integral membrane proteins that interact with their substrates, such as drugs and toxicants. An efflux transporter (e.g., P-glycoprotein) can either restrict the entry of drugs/toxicants into the testis or actively pump drugs/toxicants out of Sertoli and/or germ cells if they have entered the seminiferous epithelium via influx pumps. This thus provides an effective mechanism to safeguard spermatogenesis. Using Sertoli cells cultured in vitro with an established tight junction (TJ)-permeability barrier which mimicked the BTB in vivo and treated with cadmium chloride (CdCl2), and also in adult rats (~300 g b.w.) treated with CdCl2 (3 mg/kg b.w., via i.p.) to induce testicular injury, cadmium was found to significantly downregulate the expression of efflux (e.g., P-glycoprotein, Mrp1, Abcg1) and influx (e.g., Oatp3, Slc15a1, Scl39a8) transporters. For instance, treatment of Sertoli cells with cadmium induced significant loss of P-glycoprotein and Oatp-3 at the cell-cell interface, which likely facilitated cadmium entry into the Sertoli cell. These findings illustrate that one of the mechanisms by which cadmium enters the testis is mediated by downregulating the expression of drug transporters at the BTB. Furthermore, cytokines and steroids were found to have differential effects in regulating the expression of drug transporters. Summary, the expression of drug transporters in the testis is regulated by toxicants, steroids and cytokines.
HubMed – drug
A Blended Learning Course Design in Clinical Pharmacology for Post-graduate Dental Students.
Filed under: Drug and Alcohol Rehabilitation
Open Dent J. 2012; 6: 182-7
Rosenbaum PE, Mikalsen O, Lygre H, Solheim E, Schjøtt J
Postgraduate courses in clinical pharmacology are important for dentists to be updated on drug therapy and information related to their clinical practice, as well as knowledge of relevant adverse effects and interactions. A traditional approach with classroom delivery as the only method to teaching and learning has shortcomings regarding flexibility, individual learning preferences, and problem based learning (PBL) activities compared to online environments. This study examines a five week postgraduate course in clinical pharmacology with 15 hours of lectures and online learning activities, i.e. blended course design. Six postgraduate dental students participated and at the end of the course they were interviewed. Our findings emphasize that a blended learning course design can be successfully used in postgraduate dental education. Key matters for discussion were time flexibility and location convenience, change in teacher’s role, rein-forced learning strategies towards professional needs, scarcity in online communication, and proposed future utilization of e-learning components.
HubMed – drug
Tourette syndrome and other tic disorders in childhood, adolescence and adulthood.
Filed under: Drug and Alcohol Rehabilitation
Dtsch Arztebl Int. 2012 Nov; 109(48): 821-288
Ludolph AG, Roessner V, Münchau A, Müller-Vahl K
Tourette syndrome is a combined motor and vocal tic disorder that begins in childhood and takes a chronic course. It arises in about 1% of all children, with highly varying severity. Transient and usually mild tics are seen in as many as 15% of all children in elementary school. The diagnosis is often delayed by several years.We selectively reviewed the pertinent literature, including the guidelines of the European Society for the Study of Tourette Syndrome for the diagnosis and treatment of tic disorders.Tic disorders usually take a benign course, with spontaneous improvement in adolescence in about 90% of patients. Psychoeducation is the basis of treatment in each case and almost always brings marked emotional relief. Specific treatment is needed only for more severe tics and those that cause evident psychosocial impairment. 80-90% of patients with Tourette syndrome have comorbidities (attention deficit-hyperactivity disorder, obsessive-compulsive disorder, depression, anxiety, emotional dysregulation, autoaggression), which often impair their quality of life more than the tics do and therefore become the main target of treatment. There is little evidence for the efficacy of treatment for tics. Small-scale controlled studies with a brief follow-up period have been carried out for some neuroleptic drugs. Behavior therapy should be tried before drug treatment. A further option for very severely affected adults is deep brain stimulation.Because of the low level of the available evidence, no definitive recommendations can be made for the treatment of tics.
HubMed – drug
Evaluation of the effect of Humulus lupulus alcoholic extract on rifampin-sensitive and resistant isolates of Mycobacterium tuberculosis.
Filed under: Drug and Alcohol Rehabilitation
Res Pharm Sci. 2012 Oct; 7(4): 235-42
Serkani JE, Isfahani BN, Safaei HG, Kermanshahi RK, Asghari G
The increasing incidence of Multi Drug Resistance Tuberculosis (MDR-TB) and Extensively Drug Resistance TB (XDR-TB) worldwide highlight the urgent need to search for newer anti-tuberculosis compounds. It has been determined that pharmaceutical plant, hops (Humulus lupulus), possesses some antibacterial effect. In this study, the antimycobacterial effect of this plant on rifampin sensitive and resistant strains of Mycobacterium tuberculosis were examined. Sensitivity and resistance of 37 Iranian isolates of M. tuberculosis to rifampin was determined by proportion method. Ethanolic extract of hops was prepared using maceration method. PCR-SSCP and direct sequencing were used for confirming existence of mutations in 193-bp rpoB amplicons related to the rifampin resistance in Mycobacterium tuberculosis isolates. Two different concentrations of hops alcoholic extract (4 and 8 mg/ml) were prepared and its effects against 21 resistant and 15 sensitive isolates was determinate using proportion method. Six different mutations in the 193-bp amplified rpoB gene fragments and seven distinguishable PCR-SSCP patterns in 21 Iranian rifampin resistant isolates were recognized. This study showed that the percentage of resistance and the type of mutations were correlated with the PCR-SSCP patterns and the type of mutations in rpoB gene (P<0.05). The results of hops antimycobacterial effect showed that different concentrations of hops ethanolic extract (4 and 8 mg/ml) had a remarkable inhibitory effect on rifampin sensitive and resistant isolates of Mycobacterium tuberculosis. Identification of the effective fraction of hops against Mycobacterium tuberculosis is a further step to be studied. HubMed – drug
Effects of various penetration enhancers on percutaneous absorption of piroxicam from emulgels.
Filed under: Drug and Alcohol Rehabilitation
Res Pharm Sci. 2012 Oct; 7(4): 225-34
Shokri J, Azarmi Sh, Fasihi Z, Hallaj-Nezhadi S, Nokhodchi A, Javadzadeh Y
A suitable emulgel formulation of piroxicam was prepared and its percutaneous permeation was investigated using Wistar rat skin and diffusion cell technique. The concentrations of the drug in receptor phase of diffusion cells were measured using HPLC method. The effect of three types of penetration enhancers (Myrj 52, cineol and Transcutol P) with different concentrations on transdermal permeation of the drug was also evaluated. Flux, Kp and enhancement ratios (ERs) of piroxicam in the presence of enhancers was measured and compared with emulgel base alone and simple commercial gel. The results showed a significant enhancement in the flux from emulgel base compared to hydroalcoholic gel formulation (9.91 folds over simple gel). The highest enhancement ratio (ER=3.11) was observed for Myrj 52 at the concentration of 0.25%. Higher concentrations of Myrj 52did not show any enhancement in the drug flux due to micelle formation and solubilization of the drug by micelles. The increase in solubility, in turn, increases the saturated concentration and reduces the thermodynamic activity of the drug. Transcutol(®) P with concentrations higher than 0.25% w/w showed burst transportation of the drug through the skin. All concentrations of cineol and Transcutol did not show any enhancing effects over emulgel base alone (ER <1). HubMed – drug
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