Statin a Day Keeps Cancer at Bay.

Statin a day keeps cancer at bay.

World J Clin Oncol. 2013 May 10; 4(2): 43-6
Singh S, Singh PP

In addition to cholesterol reduction, statins, currently the most commonly prescribed drug in the world, have been shown to have anti-neoplastic and immunomodulatory effects. Several observational studies and meta-analyses have shown reduction in risk of multiple cancers. More recently there has been an increasing interest in the potential role of statins as adjuvant therapy after cancer diagnosis and in modifying cancer mortality. Although post-hoc analyses of randomized controlled trials of statins for cardiovascular outcomes have not shown reduction in the risk of cancer mortality with statin use, these studies lack sufficient power to detect a significant difference in cancer outcomes. Recently, in a Danish nationwide population-based cohort study, Nielsen et al showed a 15% reduction in all-cause and cancer-specific mortality in statin users as compared to non-users. Improved survival with statin exposure was seen in 13/27 cancer subtypes, including the 4 most common cancers – lung, prostate, colorectal and breast. In this commentary, we examine this important study, review its implications and limitations, and briefly discuss impact of other drugs like metformin and aspirin that also exhibit anti-neoplastic effects. HubMed – drug

Pseudoephedrine for the treatment of clozapine-induced incontinence.

Innov Clin Neurosci. 2013 Apr; 10(4): 33-5
Hanes A, Lee Demler T, Lee C, Campos A

Clozapine, the first atypical antipsychotic, is well known for superior efficacy in the treatment of refractory schizophrenia. Though the side effect most often associated with clozapine is the potential for causing blood dyscrasias, other lesser known side effects, including clozapine-induced incontinence, may result in the unnecessary discontinuation of this essential psychiatric medication in patients who otherwise have no alternative to treatment. Here we describe a case of pseudoephedrine used successfully as a therapeutic intervention for clozapine-induced incontinence. HubMed – drug

Dual Targeting of Insulin and Venus Kinase Receptors of Schistosoma mansoni for Novel Anti-schistosome Therapy.

PLoS Negl Trop Dis. 2013 May; 7(5): e2226
Vanderstraete M, Gouignard N, Cailliau K, Morel M, Lancelot J, Bodart JF, Dissous C

Chemotherapy of schistosomiasis relies on a single drug, Praziquantel (PZQ) and mass-use of this compound has led to emergence of resistant strains of Schistosoma mansoni, therefore pointing out the necessity to find alternative drugs. Through their essential functions in development and metabolism, receptor tyrosine kinases (RTK) could represent valuable drug targets for novel anti-schistosome chemotherapies. Taking advantage of the similarity between the catalytic domains of S. mansoni insulin receptors (SmIR1 and SmIR2) and Venus Kinase Receptors (SmVKR1 and SmVKR2), we studied the possibility to fight schistosomes by targeting simultaneously the four receptors with a single drug. METHODOLOGYPRINCIPAL FINDINGS: Several commercial RTK inhibitors were tested for their potential to inhibit the kinase activities of SmIR1, SmIR2, SmVKR1 and SmVKR2 intracellular domains (ICD) expressed in Xenopus oocytes. We measured the inhibitory effect of chemicals on meiosis resumption induced by the active ICD of the schistosome kinases in oocytes. The IR inhibitor, tyrphostin AG1024, was the most potent inhibitory compound towards SmIR and SmVKR kinases. In vitro studies then allowed us to show that AG1024 affected the viability of both schistosomula and adult worms of S. mansoni. At micromolar doses, AG1024 induced apoptosis and caused schistosomula death in a dose-dependent manner. In adult worms, AG1024 provoked alterations of reproductive organs, as observed by confocal laser scanner microscopy. With 5 µM AG1024, parasites were no more feeding and laying eggs, and they died within 48 h with 10 µM. CONCLUSIONSIGNIFICANCE: IRs and VKRs are essential in S. mansoni for key biological processes including glucose uptake, metabolism and reproduction. Our results demonstrate that inhibiting the kinase potential and function of these receptors by a single chemical compound AG1024 at low concentrations, leads to death of schistosomula and adult worms. Thus, AG1024 represents a valuable hit compound for further design of anti-kinase drugs applicable to anti-schistosome chemotherapy. HubMed – drug

Comparison of individual and pooled stool samples for the assessment of soil-transmitted helminth infection intensity and drug efficacy.

PLoS Negl Trop Dis. 2013 May; 7(5): e2189
Mekonnen Z, Meka S, Ayana M, Bogers J, Vercruysse J, Levecke B

In veterinary parasitology samples are often pooled for a rapid assessment of infection intensity and drug efficacy. Currently, studies evaluating this strategy in large-scale drug administration programs to control human soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and hookworm), are absent. Therefore, we developed and evaluated a pooling strategy to assess intensity of STH infections and drug efficacy. METHODSPRINCIPAL FINDINGS: Stool samples from 840 children attending 14 primary schools in Jimma, Ethiopia were pooled (pool sizes of 10, 20, and 60) to evaluate the infection intensity of STHs. In addition, the efficacy of a single dose of mebendazole (500 mg) in terms of fecal egg count reduction (FECR; synonym of egg reduction rate) was evaluated in 600 children from two of these schools. Individual and pooled samples were examined with the McMaster egg counting method. For each of the three STHs, we found a significant positive correlation between mean fecal egg counts (FECs) of individual stool samples and FEC of pooled stool samples, ranging from 0.62 to 0.98. Only for A. lumbricoides was any significant difference in mean FEC of the individual and pooled samples found. For this STH species, pools of 60 samples resulted in significantly higher FECs. FECR for the different number of samples pooled was comparable in all pool sizes, except for hookworm. For this parasite, pools of 10 and 60 samples provided significantly higher FECR results. CONCLUSIONSIGNIFICANCE: This study highlights that pooling stool samples holds promise as a strategy for rapidly assessing infection intensity and efficacy of administered drugs in programs to control human STHs. However, further research is required to determine when and how pooling of stool samples can be cost-effectively applied along a control program, and to verify whether this approach is also applicable to other NTDs. HubMed – drug