Drug and Alcohol Rehabilitation: Cancer Treatment Using Peptides: Current Therapies and Future Prospects.

Cancer treatment using peptides: current therapies and future prospects.

Filed under: Drug and Alcohol Rehabilitation

J Amino Acids. 2012; 2012: 967347
Thundimadathil J

This paper discusses the role of peptides in cancer therapy with special emphasis on peptide drugs which are already approved and those in clinical trials. The potential of peptides in cancer treatment is evident from a variety of different strategies that are available to address the progression of tumor growth and propagation of the disease. Use of peptides that can directly target cancer cells without affecting normal cells (targeted therapy) is evolving as an alternate strategy to conventional chemotherapy. Peptide can be utilized directly as a cytotoxic agent through various mechanisms or can act as a carrier of cytotoxic agents and radioisotopes by specifically targeting cancer cells. Peptide-based hormonal therapy has been extensively studied and utilized for the treatment of breast and prostate cancers. Tremendous amount of clinical data is currently available attesting to the efficiency of peptide-based cancer vaccines. Combination therapy is emerging as an important strategy to achieve synergistic effects in fighting cancer as a single method alone may not be efficient enough to yield positive results. Combining immunotherapy with conventional therapies such as radiation and chemotherapy or combining an anticancer peptide with a nonpeptidic cytotoxic drug is an example of this emerging field.
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Effect of Bromocriptine-QR (a Quick-Release Formulation of Bromocriptine Mesylate) on Major Adverse Cardiovascular Events in Type 2 Diabetes Subjects.

Filed under: Drug and Alcohol Rehabilitation

J Am Heart Assoc. 2012 Oct; 1(5): e002279
Gaziano JM, Cincotta AH, Vinik A, Blonde L, Bohannon N, Scranton R

Bromocriptine-QR (a quick-release formulation of bromocriptine mesylate), a dopamine D2 receptor agonist, is a US Food and Drug Administrration-approved treatment for type 2 diabetes mellitus (T2DM). A 3070-subject randomized trial demonstrated a significant, 40% reduction in relative risk among bromocriptine-QR-treated subjects in a prespecified composite cardiovascular (CV) end point that included ischemic-related (myocardial infarction and stroke) and nonischemic-related (hospitalization for unstable angina, congestive heart failure [CHF], or revascularization surgery) end points, but did not include cardiovascular death as a component of this composite. The present investigation was undertaken to more critically evaluate the impact of bromocriptine-QR on cardiovascular outcomes in this study subject population by (1) including CV death in the above-described original composite analysis and then stratifying this new analysis on the basis of multiple demographic subgroups and (2) analyzing the influence of this intervention on only the “hard” CV end points of myocardial infarction, stroke, and CV death (major adverse cardiovascular events [MACEs]).Three thousand seventy T2DM subjects on stable doses of ?2 antidiabetes medications (including insulin) with HbA1c ?10.0 (average baseline HbA1c=7.0) were randomized 2:1 to bromocriptine-QR (1.6 to 4.8 mg/day) or placebo for a 52-week treatment period. Subjects with heart failure (New York Heart Classes I and II) and precedent myocardial infarction or revascularization surgery were allowed to participate in the trial. Study outcomes included time to first event for each of the 2 CV composite end points described above. The relative risk comparing bromocriptine-QR with the control for the cardiovascular outcomes was estimated as a hazard ratio with 95% confidence interval on the basis of Cox proportional hazards regression. The statistical significance of any between-group difference in the cumulative percentage of CV events over time (derived from a Kaplan-Meier curve) was determined by a log-rank test on the intention-to-treat population. Study subjects were in reasonable metabolic control, with an average baseline HbA1c of 7.0±1.1, blood pressure of 128/76±14/9, and total and LDL cholesterol of 179±42 and 98±32, respectively, with 88%, 77%, and 69% of subjects being treated with antidiabetic, antihypertensive, and antihyperlipidemic agents, respectively. Ninety-one percent of the expected person-year outcome ascertainment was obtained in this study. Respecting the CV-inclusive composite cardiovascular end point, there were 39 events (1.9%) among 2054 bromocriptine-QR-treated subjects versus 33 events (3.2%) among 1016 placebo subjects, yielding a significant, 39% reduction in relative risk in this end point with bromocriptine-QR exposure (P=0.0346; log-rank test) that was not influenced by age, sex, race, body mass index, duration of diabetes, or preexisting cardiovascular disease. In addition, regarding the MACE end point, there were 14 events (0.7%) among 2054 bromocriptine-QR-treated subjects and 15 events (1.5%) among 1016 placebo-treated subjects, yielding a significant, 52% reduction in relative risk in this end point with bromocriptine-QR exposure (P<0.05; log-rank test).These findings reaffirm and extend the original observation of relative risk reduction in cardiovascular adverse events among type 2 diabetes subjects treated with bromocriptine-QR and suggest that further investigation into this impact of bromocriptine-QR is warranted.URL: http://clinicaltrials.gov. Unique Identifier: NCT00377676. HubMed – drug


Ablation for atrial fibrillation in combination with left atrial appendage closure: first results of a feasibility study.

Filed under: Drug and Alcohol Rehabilitation

J Am Heart Assoc. 2012 Oct; 1(5): e002212
Swaans MJ, Post MC, Rensing BJ, Boersma LV

Drug-refractory atrial fibrillation (AF) increasingly is being treated with catheter ablation. However, the long-term success rate, expressed as freedom from AF, is <50%. Therefore, vitamin K antagonists, with all their complications, remain necessary. Recently, left atrial appendage (LAA) occlusion devices were introduced as an alternative to vitamin K antagonists. Here, we investigated whether AF ablation and LAA occlusion could be a feasible and safe combination in patients with symptomatic drug-refractory AF and a CHADS(2) score ?1 or a contraindication for vitamin K antagonists.Ablation was performed by using multielectrode catheters with phased radiofrequency energy. LAA was occluded with the Watchman device (Atritech, Inc, Plymouth, MN). Between February 2010 and February 2011, 30 patients were treated (21 male; age, 62.8±8.5 years). Median CHADS(2) score was 2.5 (25th to 75th percentiles: 2 to 3), median CHADS-VASc score was 3 (25th to 75th percentiles: 3 to 5), 77% had prior stroke, and 27% had a contraindication for vitamin K antagonists. Median HAS-BLED score was 2 (range, 1 to 5). Successful device implantation was achieved with a median number of 1.5 devices (median diameter 24 mm [25th to 75th percentiles: 24 to 24 mm]). Total procedure time was 97 minutes (25th to 75th percentiles: 75 to 115 minutes). At 60 days, all patients met the criteria for successful sealing. Follow-up visit at 12 months showed a 30% rate of documented recurrence of AF. A repeated pulmonary vein isolation was performed successfully in 4 patients, without interference of the LAA closure device. No thromboembolic events occurred during 1-year follow-up.LAA occlusion with the Watchman device and AF ablation can be combined successfully and safely in a single procedure. The Watchman does not interfere with a repeated ablation. HubMed – drug


Anxiolytic effects of flavonoids in animal models of posttraumatic stress disorder.

Filed under: Drug and Alcohol Rehabilitation

Evid Based Complement Alternat Med. 2012; 2012: 623753
Zhang LM, Yao JZ, Li Y, Li K, Chen HX, Zhang YZ, Li YF

The dysregulation of the serotonergic system has long been recognized as an important factor underlying the pathophysiology of PTSD. To date, SSRIs have already been established as the firstline pharmacotherapeutic agents for treating acute and chronic PTSD. However, SSRIs largely have several disadvantages which limit their utility. Our previous study has also shown that administration of the total flavonoids, isolated from the extract of Xiaobuxin-Tang (XBXT, mild mind-easing decoction), comprising four Chinese medicines including Haematitum, Flos Inulae, Folium Phyllostachydis Henonis, and Semen Sojae Preparatum, exerted significant antidepressant-like effect in chronically mildly stressed rats, possibly mediated by serotonergic activation. Since the central serotonergic dysfunction is an important and well-known cause mediating the pathophysiology of trauma-related symptoms in PTSD, it is reasonable to predict that flavonoids may exert therapeutic effects on PTSD in animal models. Therefore, the present study aims to examine the effect of flavonoids in alleviating the enhanced anxiety and fear response induced in two PTSD animal models. Ser, an SSRI, was administered as a positive control. Furthermore, the changes of brain monoaminergic neurotransmitters after chronic flavonoids administration have also been assessed in SPS-treated rats.
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