Current Drug Therapy (v.8, #1)

Benzimidazole Derivatives as Potential Chemotherapeutic Agents by Ahmed A. El Rashedy, Hassan Y. Aboul-Enein (1-14).
Benzimidazoles exhibit a broad range of biological activities. Several benzimidazoles are used in therapy suchas albendazole, mebendazole, flubendazole, fenbendazole, omeprazole, lansoprazole,clofazimine. Benzimidazolederivatives play a vital role in the biological field such as antimicrobial, antiviral, antidiabetic, antiulcer and anticanceractivities. The present review highlights the recently synthesized benzimidazoles possessing important potential biologicalactivities as chemotherapeutic agents.

Cancer is a worldwide leading cause of death. Multiple genetic mutations or environmental influences lead tothe change of cellular functions that result in malignant transformation. Therapeutic approaches, such as surgery,chemotherapy and radiotherapy have harmful side effects due to their inability to specifically target particular tumors.Each therapeutic strategy is aimed to affect the target tumor cells with minimum toxic effects on the function of thenormal cells. Specific targeted therapy offers the hope of improving the treatment of cancer resistant to conventionaltherapy. A better understanding of the molecular pathogenesis of cancer has contributed to the development of specificnovel drugs, including monoclonal antibodies, small molecule inhibitors, mimetic, antisense and small interference RNA.The use of cancer vaccines for the specific treatment of cancer has recently increased, as they are able to generate anactive tumor-specific immune response. However, the treatment of cancer with specific peptides/proteins, genes, and shortinterfering RNA (siRNA) is very promising, using cell penetrating peptides for their delivery into the cells. Thesecompounds act on specific targets that are believed to contribute to the development and progression of cancers and theresistance of tumors to conventional therapies. Delivered individually or in combination with chemo- and/or radiotherapy,such novel drugs have produced significant responses in certain types of tumors. This review describes these differentstrategies which provide some insight into the future direction of the eradication of cancer cells altogether.

Cancer Metastasis Treatments by Da-Yong Lu, Ting-Ren Lu, Hong-Ying Wu, Shan Cao (24-29).
More than 90% of cancer deaths are caused by cancer metastasis. Since cancer metastasis is the main cause ofhuman deaths, so in this article more attention will be paid to it than ever before. Presently, clinical cancer chemotherapieshave been targeting on primary tumors rather than on metastatic processes. Since the antimetastatic drugs are differentfrom antiproliferative drugs and underinvestigated, cancer patients? survival has been improved on a small scale now. Tochange this stalemate, this problem is reiterated by an analysis of the relationship between pathology, pharmacology andclinical therapy of neoplasm metastasis and it is suggested to improve the outcome of chemotherapy of cancer patientsfrom different possible ways; e.g. to make more efforts to manufacture new types of antimetastatic drugs and optimize useof these drugs in clinics.

Background: Early treatment for infertile women with polycystic ovary syndrome (PCOS) is likely crucial andincludes mainly clomiphene citrate (CC) and metformin.</P><P>Objectives: To review the literature data regarding the use of CC, metformin, or both for the treatment of infertility inanovulatory patients with PCOS.</P><P>Materials and Methods: Using PubMed database, all main relevant articles studying therapy na?ve patients with PCOSwho received CC, metformin or both were searched, reviewed and analyzed.</P><P>Main Results and Conclusions: In infertile obese PCOS patients, CC is the therapy of choice for inducing ovulation.Combining CC and metformin is not more effective than CC alone. Further studies are needed to define the best first linetreatment in non-obese PCOS patients.

Comparison of Gentamicin Ointment to Mupirocin Ointment for Prevention of Peritoneal Dialysis Catheter-Related Infections by Katherine Wu, Erica Greanya, Karen Shalansky, Nadia Zalunardo, Guiyun Li, Suneet Singh (38-44).
In July 2007, all peritoneal dialysis (PD) patients in our hospital were switched from mupirocin to gentamicinointment for daily application to the PD catheter exit site (CES). Our objective was to compare the efficacy of gentamicinand mupirocin in the prevention of catheter-related PD infections. We conducted an observational sequential cohort studyto compare infectious outcomes with the 2 ointments. Mupirocin patients were followed retrospectively from January2004 to June 2006 and gentamicin patients prospectively from July 2007 to December 2008. All patients were followedfor 18 months following catheter insertion. Fifty-nine patients were included in the mupirocin arm and 37 patients in thegentamicin arm. Time to first infection (either CES or peritonitis) was similar between arms, with a probability of beinginfection-free at 12 months of 67% versus 53%, respectively (p=0.34). There were no differences in rates of overallinfection (0.54 vs 0.56 infections per patient-year, respectively (p=0.94)) or peritonitis (0.41 vs 0.37 per patient-year,respectively (p=0.84). There were 5 pseudomonal infections in the mupirocin arm and none with gentamicin. It wasconcluded that topical gentamicin has comparable effectiveness to mupirocin for prevention of PD catheter-relatedinfections.

Safety of Anti-TNF Alpha Agents in the Pregnant Psoriatic Patient by Laurie K. Shallcross, Marcia S. Driscoll (45-58).
Psoriasis is a chronic, often difficult to control condition which accounts for significant morbidity worldwide.The United States Food and Drug Administration (FDA) approved multiple TNF alpha blockers in the 21st century for thetreatment of psoriasis. These agents provide an alternative treatment approach for those with moderate to severe psoriasis,who fail to respond adequately to traditional therapies. The increasing use of these agents in women of childbearing ageraises questions concerning their safety in the pregnant psoriatic patient. A review of case reports and registry data wasperformed on the outcomes of pregnancies in psoriatic patients and in those with other inflammatory conditions who wereexposed to these biologic agents. To date, it remains inadvisable to continue pregnant patients on these medications ifalternative, well-established therapies are effective. However, for those women unable to tolerate alternative treatments orwho are inadvertently exposed to TNF-alpha inhibitors during pregnancy, the published data do not indicate an increasedrisk of fetal malformation or a need to recommend pregnancy termination. Transplacental transfer of these drugs isgreatest during the last two trimesters of pregnancy, which may result in persistent detectable drug levels in the newborninfant. If a fetus is exposed to TNF alpha blockers toward the end of pregnancy, then live vaccinations in these infantsshould be delayed until drug levels in infant serum are undetectable, or for at least 6-7 months if levels cannot bemeasured.

Microbicides for Prevention of AIDS by Ram S. Thakur, Arshad B. Khan (59-67).
Microbicides as a potential intervention strategy for preventing human immunodeficiency virus (HIV)transmission, provide women with a preventive option against HIV. For more than two decades, various studies haveendeavored to find effective and safe microbicides, which would provide defense against HIV/AIDS. Microbicidesinclude various agents having different mechanisms such as, disruption of cellular and microbial membranes (surfactants),restoration of the natural acidic protective pH of the vagina (acid buffers), interference interactions between HIV envelopeproteins and cellular receptors (anionic polymers), and anti retroviral agents. This review presents the progress indevelopment of microbicides in prevention of spread of HIV.