Effect of Clonidine (An Antihypertensive Drug) Treatment on Oxidative Stress Markers in the Heart of Spontaneously Hypertensive Rats.

Effect of Clonidine (an Antihypertensive Drug) Treatment on Oxidative Stress Markers in the Heart of Spontaneously Hypertensive Rats.

Oxid Med Cell Longev. 2013; 2013: 927214
Nik Yusoff NS, Mustapha Z, Govindasamy C, Sirajudeen KN

Hypertension is a risk factor for several cardiovascular diseases and oxidative stress suggested to be involved in the pathophysiology. Antihypertensive drug Clonidine action in ameliorating oxidative stress was not well studied. Therefore, this study investigate the effect of Clonidine on oxidative stress markers and nitric oxide (NO) in SHR and nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME) administered SHR. Male rats were divided into four groups [SHR, SHR+Clonidine (SHR-C), SHR+L-NAME, SHR+Clonidine+L-NAME(SHRC+L-NAME)]. Rats (SHRC) were administered with Clonidine (0.5?mg kg(-1)?day(-1)) from 4 weeks to 28 weeks in drinking water and L-NAME (25?mg kg(-1)?day(-1)) from 16 weeks to 28 weeks to SHRC+L-NAME. Systolic blood pressure (SBP) was measured. At the end of 28 weeks, all rats were sacrificed and in their heart homogenate, oxidative stress parameters and NO was assessed. Clonidine treatment significantly enhanced the total antioxidant status (TAS) (P < 0.001) and reduced the thibarbituric acid reactive substances (TBARS) (P < 0.001) and protein carbonyl content (PCO) (P < 0.05). These data suggest that oxidative stress is involved in the hypertensive organ damage and Clonidine not only lowers the SBP but also ameliorated the oxidative stress in the heart of SHR and SHR+L-NAME. HubMed – drug


Duloxetine for the treatment of post-prostatectomy stress urinary incontinence.

Can Urol Assoc J. 2013 May; 7(5-6): E260-2
Neff D, Guise A, Guralnick ML, Langenstroer P, See WA, Jacobsohn KM, O’Connor RC

Stress urinary incontinence (SUI) is a known complication following prostatectomy. Duloxetine, a combined serotonin/norepinephrine reuptake inhibitor, can decrease SUI by increasing urethral sphincter contractility. We examined the outcomes of patients with mild to moderate post-prostatectomy SUI treated with duloxetine.We conducted a retrospective review of men treated with duloxetine to manage mild to moderate post-prostatectomy SUI from 2006 to 2012. All patients received oral duloxetine 30 mg once a week, then 60 mg thereafter. Patients were seen one month later to determine drug efficacy and side effects.In total, 94 men were included in the study. Daily pad usage decreased from 2.9 (range: 1-5) to 1.6 (range: 0-4) (p < 0.05). Incontinence Impact Questionnaire (IIQ-7) scores decreased from 13.0 (range: 6-18) to 7.9 (range: 2-16) (p < 0.05). Linear satisfaction scores improved from 0.8 (range: 0-2) to 2.0 (range: 1-3) (p < 0.05). Following a 1-month duloxetine trial, 33/94 (35%) men reported satisfactory SUI improvement and requested to continue the medication. The drug was discontinued in 61/94 (65%) patients due to poor efficacy in 32/94 (34%), intolerable side effects in 14/94 (15%) or both in 15/94 (16%). Reported side effects included fatigue, light-headedness, insomnia, nausea and dry mouth.Duloxetine improved post-prostatectomy SUI in 47/94 (50%) men following a 1-month trial. However, only 33/94 (35%) patients were able to tolerate the drug. Duloxetine may be considered a treatment option for men with mild to moderate post-prostatectomy SUI. HubMed – drug


Reversible maleimide-thiol adducts yield glutathione-sensitive poly(ethylene glycol)-heparin hydrogels.

Polym Chem. 2013 Jan 7; 4(1): 133-143
Baldwin AD, Kiick KL

We have recently reported that retro Michael-type addition reactions can be employed for producing labile chemical linkages with tunable sensitivity to physiologically relevant reducing potentials. We reasoned that such strategies would also be useful in the design of glutathione-sensitive hydrogels for a variety of targeted delivery and tissue engineering applications. In this report, we describe hydrogels in which maleimide-functionalized low molecular weight heparin (LMWH) is crosslinked with various thiol-functionalized poly(ethylene glycol) (PEG) multi-arm star polymers. Judicious selection of the chemical identity of the thiol permits tuning of degradation via previously unstudied, but versatile chemical methods. Thiol pKa and hydrophobicity affected both the gelation and degradation of these hydrogels. Maleimide-thiol crosslinking reactions and retro Michael-type addition reactions were verified with (1)H NMR during the crosslinking and degradation of hydrogels. PEGs esterified with phenylthiol derivatives, specifically 4-mercaptophenylpropionic acid or 2,2-dimethyl-3-(4-mercaptophenyl)propionic acid, induced sensitivity to glutathione as shown by a decrease in hydrogel degradation time of 4-fold and 5-fold respectively, measured via spectrophotometric quantification of LMWH. The degradation proceeded through the retro Michael-type addition of the succinimide thioether linkage, with apparent pseudo-first order reaction constants derived from oscillatory rheology experiments of 0.039 ± 0.006 h(-1) and 0.031 ± 0.003 h(-1). The pseudo-first order retro reaction constants were approximately an order of magnitude slower than the degradation rate constants for hydrogels crosslinked via disulfide linkages, indicating the potential use of these Michael-type addition products for reduction-mediated release and/or degradation, with increased blood stability and prolonged drug delivery timescales compared to disulfide moieties. HubMed – drug


TIPdb: A Database of Anticancer, Antiplatelet, and Antituberculosis Phytochemicals from Indigenous Plants in Taiwan.

ScientificWorldJournal. 2013; 2013: 736386
Lin YC, Wang CC, Chen IS, Jheng JL, Li JH, Tung CW

The unique geographic features of Taiwan are attributed to the rich indigenous and endemic plant species in Taiwan. These plants serve as resourceful bank for biologically active phytochemicals. Given that these plant-derived chemicals are prototypes of potential drugs for diseases, databases connecting the chemical structures and pharmacological activities may facilitate drug development. To enhance the utility of the data, it is desirable to develop a database of chemical compounds and corresponding activities from indigenous plants in Taiwan. A database of anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan was constructed. The database, TIPdb, is composed of a standardized format of published anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan. A browse function was implemented for users to browse the database in a taxonomy-based manner. Search functions can be utilized to filter records of interest by botanical name, part, chemical class, or compound name. The structured and searchable database TIPdb was constructed to serve as a comprehensive and standardized resource for anticancer, antiplatelet, and antituberculosis compounds search. The manually curated chemical structures and activities provide a great opportunity to develop quantitative structure-activity relationship models for the high-throughput screening of potential anticancer, antiplatelet, and antituberculosis drugs. HubMed – drug