Mycobacterium Fluoroquinolone Resistance Protein B, a Novel Small GTPase, Is Involved in the Regulation of DNA Gyrase and Drug Resistance.

Mycobacterium fluoroquinolone resistance protein B, a novel small GTPase, is involved in the regulation of DNA gyrase and drug resistance.

Filed under: Drug and Alcohol Rehabilitation

Nucleic Acids Res. 2012 Dec 28;
Tao J, Han J, Wu H, Hu X, Deng J, Fleming J, Maxwell A, Bi L, Mi K

DNA gyrase plays a vital role in resolving DNA topological problems and is the target of antibiotics such as fluoroquinolones. Mycobacterium fluoroquinolone resistance protein A (MfpA) from Mycobacterium smegmatis is a newly identified DNA gyrase inhibitor that is believed to confer intrinsic resistance to fluoroquinolones. However, MfpA does not prevent drug-induced inhibition of DNA gyrase in vitro, implying the involvement of other as yet unknown factors. Here, we have identified a new factor, named Mycobacterium fluoroquinolone resistance protein B (MfpB), which is involved in the protection of DNA gyrase against drugs both in vivo and in vitro. Genetic results suggest that MfpB is necessary for MfpA protection of DNA gyrase against drugs in vivo; an mfpB knockout mutant showed greater susceptibility to ciprofloxacin than the wild-type, whereas a strain overexpressing MfpA and MfpB showed higher loss of susceptibility. Further biochemical characterization indicated that MfpB is a small GTPase and its GTP bound form interacts directly with MfpA and influences its interaction with DNA gyrase. Mutations in MfpB that decrease its GTPase activity disrupt its protective efficacy. Our studies suggest that MfpB, a small GTPase, is required for MfpA-conferred protection of DNA gyrase.
HubMed – drug


Pregnancy in a Patient With Adrenal Carcinoma Treated With Mitotane: A Case Report and Review of Literature.

Filed under: Drug and Alcohol Rehabilitation

J Clin Endocrinol Metab. 2012 Dec 28;
Tripto-Shkolnik L, Blumenfeld Z, Bronshtein M, Salmon A, Jaffe A

Context:Adrenocortical carcinoma (ACC) affects patients in a broad age group, including young women. Mitotane, an adrenolytic agent, is the mainstay of treatment after surgical removal of the tumor. There is extreme paucity of information regarding the effect of mitotane on childbearing potential and pregnancy outcome.Objective:The aim of the study was to describe and discuss the case of an ACC patient who conceived while on mitotane treatment. Current literature is reviewed.Patient and Methods:A 33-year-old woman received mitotane treatment for 4 years due to metastatic ACC. Despite nearly therapeutic blood levels of the drug, the patient had regular menstruation and was able to conceive. Mitotane was stopped at gestation week 6. Although the drug continued to be detected in considerable amounts, the fetus developed normally, including morphologically intact adrenal glands. At gestation week 21, pregnancy was terminated due to ACC recurrence. Mitotane levels were undetectable in fetal cord blood and amniotic fluid.Conclusion:Our report suggests that mitotane, despite its action as an endocrine disruptor, does not affect normal gonadal function or an ability to conceive. The concern of placental transfer by this hydrophobic compound is not supported by our findings. However, we do not recommend drawing conclusions regarding the safety of mitotane in pregnancy, based on 1 or several case reports. Until more data are available, pregnancy should be avoided in women being treated with mitotane for ACC.
HubMed – drug


Malaria “Diagnosis” and Diagnostics in Afghanistan.

Filed under: Drug and Alcohol Rehabilitation

Qual Health Res. 2012 Dec 28;
Reynolds J, Wood M, Mikhail A, Ahmad T, Karimullah K, Motahed M, Hazansai A, Baktash SH, Anwari N, Kizito J, Mayan I, Rowland M, Chandler C, Leslie T

In many malaria-endemic areas, including Afghanistan, overdiagnosis of malaria is common. Even when using parasite-based diagnostic tests prior to treatment, clinicians commonly prescribe antimalarial treatment following negative test results. This practice neglects alternative causes of fever, uses drugs unnecessarily, and might contribute to antimalarial drug resistance. We undertook a qualitative study among health workers using different malaria diagnostic methods in Afghanistan to explore perceptions of malaria diagnosis. Health workers valued diagnostic tests for their ability to confirm clinical suspicions of malaria via a positive result, but a negative result was commonly interpreted as an absence of diagnosis, legitimizing clinical diagnosis of malaria and prescription of antimalarial drugs. Prescribing decisions reflected uncertainty around tests and diagnosis, and were influenced by social- and health-system factors. Study findings emphasize the need for nuanced and context-specific guidance to change prescriber behavior and improve treatment of malarial and nonmalarial febrile illnesses.
HubMed – drug


Impact of Diabetes on Long-Term Outcome After Primary Angioplasty: Insights from the DESERT cooperation.

Filed under: Drug and Alcohol Rehabilitation

Diabetes Care. 2012 Dec 28;
De Luca G, Dirksen MT, Spaulding C, Kelbæk H, Schalij M, Thuesen L, van der Hoeven B, Vink MA, Kaiser C, Musto C, Chechi T, Spaziani G, Diaz de la Llera LS, Pasceri V, Di Lorenzo E, Violini R, Suryapranata H, Stone GW,

OBJECTIVEDiabetes has been shown to be associated with worse survival and repeat target vessel revascularization (TVR) after primary angioplasty. The aim of the current study was to evaluate the impact of diabetes on long-term outcome in patients undergoing primary angioplasty treated with bare metal stents (BMS) and drug-eluting stents (DES).RESEARCH DESIGN AND METHODSOur population is represented by 6,298 ST-segment elevation myocardial infarction (STEMI) patients undergoing primary angioplasty included in the DESERT database from 11 randomized trials comparing DES with BMS.RESULTSDiabetes was observed in 972 patients (15.4%) who were older (P < 0.001), more likely to be female (P < 0.001), with higher prevalence of hypertension (P < 0.001), hypercholesterolemia (P < 0.001), and longer ischemia time (P < 0.001), and without any difference in angiographic and procedural characteristics. At long-term follow-up (1,201 ± 441 days), diabetes was associated with higher rates of death (19.1% vs 7.4%; P < 0.0001), reinfarction (10.4% vs 7.5%; P < 0.001), stent thrombosis (7.6% vs 4.8%; P = 0.002) with similar temporal distribution-acute, subacute, late, and very late-between diabetes and control patients, and TVR (18.6% vs 15.1%; P = 0.006). These results were confirmed in patients receiving BMS or DES, except for TVR, there being no difference observed between diabetic and nondiabetic patients treated with DES. The impact of diabetes on outcome was confirmed after correction for baseline confounding factors (mortality, P < 0.001; repeat myocardial infarction, P = 0.006; stent thrombosis, P = 0.007; TVR, P = 0.027).CONCLUSIONSThis study shows that among STEMI patients undergoing primary angioplasty, diabetes is associated with worse long-term mortality, reinfarction, and stent thrombosis in patients receiving DES and BMS. DES implantation, however, does mitigate the known deleterious effect of diabetes on TVR after BMS. HubMed – drug



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