Drug and Alcohol Rehabilitation: Computational Analysis to Predict Functional Role of Hsa-miR-3065-3p as an Antiviral Therapeutic Agent for Treatment of Triple Infections: HCV, HIV-1, and HBV.

Computational analysis to predict functional role of hsa-miR-3065-3p as an antiviral therapeutic agent for treatment of triple infections: HCV, HIV-1, and HBV.

Filed under: Drug and Alcohol Rehabilitation

Libyan J Med. 2012; 7:
Khokhar A, Noorali S, Sheraz M, Mahalingham K, Pace DG, Khanani MR, Bagasra O

Triple infection (TI) with HIV-1, HCV, and HBV (TI) is highly prevalent in intravenous drug users (IDUs). These TI patients have a faster progression to AIDS, and even after antiretroviral therapy (ART) the prognosis of their disease is poor. The use of microRNA (miRNA) to silence genes holds potential applications for anti-HCV therapy.We analyzed the role of human miRNAs (hsa-miRs) in TI by computational analyses for HCV, HIV-1, and HBV showing identity to these three viral genomes.We identified one unique miRNA, hsa-miR-3065-3p, that shares significant mutual identity to these three viral genomes (?61-83%). In addition, hsa-miR-99, hsa-miR-548, and hsa-miR-122 also showed mutual identity with these three viral genomes, albeit at a lower degree (?52-88%).Here, we present evidence using essential components of bioinformatics tools, and hypothesize that utility of hsa-miR-3065-3p and perhaps miR-548 would be potential antiviral therapeutic agents in the treatment of TI patients because it shows near perfect alignment in the seed region for all three viruses. We also make an argument that current proposed therapy with hsa-miR-122 may not be the optimal choice for HCV patients since it lacks essential gene alignment and may be harmful for the patients.
HubMed – drug

Adherence to Calcium and Vitamin D supplementations: results from the ADVICE Survey.

Filed under: Drug and Alcohol Rehabilitation

Clin Cases Miner Bone Metab. 2012 Sep; 9(3): 157-60
Conti F, Piscitelli P, Italiano G, Parma A, Caffetti MC, Giolli L, Di Tanna GL, Guazzini A, Brandi ML

The ADVICE (ADherence in VItamin-D and Calcium Embedded or not) survey was aimed to evaluate the effect of a patient-focused motivation strategy on the adherence to calcium and vitamin D supplementation. The survey also intended to identify possible factors being able to influence the compliance (i.e. the existence of individual preferences towards different dosages or regimens of supplementation).We planned to involve consecutive patients visited between 2010 and 2011 at 35 centres specialized in diagnosis and treatment of osteoporosis in different Italian regions. Each patient has been requested to declare if he/she was already assuming any supplementation with calcium and vitamin D (naïve or not naïve). All patients underwent a first visit (T0) and two follow up visits at 6 and 12 months (T6 e T12). The assessment of the adherence was measured through the Morinsky Medication Adherence Scale, a score based on 8 different questions, specifically validated to determine therapeutical compliance (0-5: not acceptable; 6-7: acceptable; 8: ideal).732 women (mean age: 66.9; average BMI: 25.3) and 30 men (mean age: 71.9; average BMI: 24.5) were enrolled; 34% of female patients (n=245) and 66% of males (n=20) reported previous fractures. Not naïve patients were 385 (54%). A total of 309 patients (43%) were concurrently assuming an antifracture drug; 229 subjects were osteoporotic (45%), while 224 were osteopenic (44%). The mean Morinsky score in not naïve patients was 5.72, 6.19 and 6.18 at T0, T6, and T12, respectively. Thus, no differences in the Morinsky score were observed between T6 and T12. Naïve patients showed an average Morinsky score of 5.78 at T6 and 6.39 at T12. Older age was not significantly associated with the observed changes in the scores. The onset of AEs related to the supplementation with calcium and vitamin D was able to negatively influence the adherence at the subsequent control point. Bone mineral density, previous fractures, and concurrent assumption of any antifracture drug did not significantly influence the adherence, as well as the differences in the dosages or regimens of calcium and vitamin D administration.Activities aimed to strengthen motivation of the patients improved the adherence to calcium and vitamin D supplementations after only 6 months.
HubMed – drug

Increased Locomotor Activity and Non-Selective Attention and Impaired Learning Ability in SD Rats after Lentiviral Vector-Mediated RNA Interference of Homer 1a in the Brain.

Filed under: Drug and Alcohol Rehabilitation

Int J Med Sci. 2013; 10(1): 90-102
Hong Q, Yang L, Zhang M, Pan XQ, Guo M, Fei L, Tong ML, Chen RH, Guo XR, Chi X

Our previous studies found that Homer 1a, a scaffolding protein localized at the post-synaptic density (PSD) of glutamatergic excitatory synapses, is significantly down-regulated in the brain of spontaneous hypertensive rats (SHR), an animal model of attention deficit hyperactivity disorder (ADHD). Furthermore, a first-line treatment drug for ADHD, methylphenidate, can up-regulate the expression of Homer 1a. To investigate the possible role of Homer 1a in the etiology and pathogenesis of ADHD, a lentiviral vector containing miRNA specific for Homer 1a was constructed in this study. Intracerebroventricular injection of this vector into the brain of Sprague Dawley (SD) rats significantly decreased Homer 1a mRNA and protein expression levels. Compared to their negative controls, these rats displayed a range of abnormal behaviors, including increased locomotor activity and non-selective attention and impaired learning ability. Our results indicated that Homer 1a down-regulation results in deficits in control over behavioral output and learning similar to ADHD.
HubMed – drug

Factors influencing vancomycin loading dose for hospitalized hemodialysis patients: prospective observational cohort study.

Filed under: Drug and Alcohol Rehabilitation

Can J Hosp Pharm. 2012 Nov; 65(6): 436-42
El Nekidy WS, El-Masri MM, Umstead GS, Dehoorne-Smith M

The increasing use of vancomycin to treat methicillin-resistant Staphylococcus aureus (MRSA) has resulted in reduced susceptibility of MRSA to this drug. It is important to optimize vancomycin dosing in patients who are undergoing hemodialysis to attain a pre-hemodialysis serum concentration sufficient to eradicate MRSA, in accordance with recent guideline recommendations.To establish the optimal strategy for vancomycin loading dose in patients undergoing hemodialysis and to explore the determinants of pre-hemodialysis serum concentration of vancomycin measured in these patients.A prospective observational cohort study was conducted between January and June 2010. Eligible participants were adults with established stage 5 chronic kidney disease who were undergoing inpatient hemodialysis. Data were collected on loading dose administered, body weight, serum concentration of vancomycin before the subsequent hemodialysis session (pre-hemodialysis concentration), and time between end of vancomycin infusion and measurement of pre-hemodialysis serum concentration. Multivariate stepwise linear regression was performed to examine independent associations between variables and measured pre-hemodialysis serum concentration of vancomycin.Eighty-one patients were included in the study. Of 24 patients who achieved the recommended pre-hemodialysis serum concentration of vancomycin (15-20 mg/L), 14 had a loading dose between 15 and 20 mg/kg. Further analysis suggested that the pre-hemodialysis serum concentration of vancomycin was independently associated with weight-based loading dose (mg/kg) (ß = 0.293, p = 0.003), age (ß = -0.358, p < 0.001), and time between administration of the loading dose and initiation of hemodialysis (ß = -0.247, p = 0.011).The findings of this study indicate that a loading dose of 15-20 mg/kg (actual body weight) is likely to yield an optimal pre-hemodialysis serum concentration at a median elapsed time of 24 h. In addition to loading dose, patient age and time between administration of the loading dose and initiation of hemodialysis also influenced the pre-hemodialysis serum concentration of the drug. HubMed – drug

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