Prescribing patterns of antimicrobials in the Internal Medicine Department of Ibrahim Malik Teaching Hospital in Khartoum, 2016.

INTRODUCTION: Antimicrobials are among the most commonly prescribed therapeutic agents in hospitals. Irrational use of antimicrobials results in the development of antimicrobial resistance which could lead to life-threatening illnesses. Therefore, the assessment of antimicrobial prescribing and use is of utmost importance. This study aimed to examine the prescribing patterns of antimicrobials in the Internal Medicine Department of Ibrahim Malik Teaching Hospital in Khartoum, Sudan. METHODS: A descriptive, cross-sectional study was conducted using World Health Organization (WHO) indicators for antimicrobial use in hospitals. Systematic random sampling was used to select 245 medical records from the 2613 medical records of patients admitted to the internal medicine department in 2016. Data were collected using a data collection form and a structured interview with the chief pharmacist in the hospital. RESULTS: Of the 245 medical records examined, 201 (82%) patients were prescribed one or more antimicrobial drug. The average number of antimicrobials per patient was (2.1±1.1). The average duration of antimicrobial treatment was (4.9±3.8) days. The generic name was used in (35.6%) of antimicrobials, while (95.5%) of all antimicrobials were prescribed from the national essential medicines list. Overall, there were 421 courses of antimicrobials prescribed. The most frequently prescribed antimicrobials were ceftriaxone (131 courses) and metronidazole (89 courses). Among the documented infectious diseases, the most frequently encountered was pneumonia, followed by malaria. There was no drug and therapeutic committee, hospital formulary or essential medicines list, and standard treatment guidelines for infectious diseases in the hospital. CONCLUSION: The results of the study revealed a high percentage of antimicrobial use in the Internal Medicine Department. Multifaceted interventions are urgently needed to promote rational prescribing of antimicrobials.

Role of Inflammatory and Oxidative Stress, Cytochrome P450 2E1, and Bile Acid Disturbance in Rat Liver Injury Induced by Isoniazid and Lipopolysaccharide Cotreatment.

Isoniazid (INH) remains the core drug in tuberculosis management, but serious hepatotoxicity and potentially fatal liver injury continue to accompany INH consumption. Among numerous theories that have been established to explain INH-induced liver injury, an inflammatory stress theory has recently been widely used to explain the idiosyncrasy. Inflammatory stress usually sensitizes tissues to a drug's toxic consequences. Therefore, the present study was conducted to verify whether bacterial lipopolysaccharide (LPS)-induced inflammation may have a role in enhancing INH hepatotoxicity. While single INH or LPS administration showed no major toxicity signs, INH-LPS cotreatment intensified liver toxicity. Both blood biomarkers and histological evaluations clearly showed positive signs of severe liver damage accompanied by massive necrosis, inflammatory infiltration, and hepatic steatosis. Furthermore, elevated serum levels of bile acid associated with the repression of bile acid synthesis and transport regulatory parameters were observed. Moreover, the principal impact of cytochrome P450 2E1 (CYP2E1) on INH toxicity could be anticipated, as its protein expression showed enormous increases in INH-LPS-cotreated animals. Furthermore, the crucial role of CYP2E1 in the production of reactive oxygen species (ROS) was clearly obvious in the repression of hepatic antioxidant parameters. In summary, these results confirmed that this LPS-induced inflammation model might prove valuable in revealing the hepatotoxic mechanisms of INH and the crucial role played by CYP2E1 in the initiation and propagation of INH-induced liver damage, information which could be very useful to clinicians in understanding the pathogenesis of drug-induced liver injury.

The potential utility of acetyltanshinone IIA in the treatment of HER2-overexpressed breast cancer: Induction of cancer cell death by targeting apoptotic and metabolic signaling pathways.

Increased lipogenesis and protein synthesis is a hallmark of cancer cell proliferation, survival, and metastatic progression and is under intense investigation as a potential antineoplastic target. Acetyltanshinone IIA (ATA) is a compound that was obtained from chemical modifications of tanshinone IIA (TIIA), a potent anticancer agent extracted from the dried roots of the Chinese herbal medicine Salvia miltiorrhiza Bunge. A previous investigation indicated that ATA is more effective in inhibiting the growth of breast cancer especially cells with HER2 overexpression. However, the molecular mechanism(s) mediating this cytotoxic effect on HER2-positive breast cancer remained undefined. Studies described here report that ATA induced G1/S phase arrest and apoptosis in the HER2-positive MDA-MB-453, SK-BR-3, and BT-474 breast cancer cell lines. Mechanistic investigations revealed that the ATA-induced apoptosis effect is associated with remarkably down-regulation of receptor tyrosine kinases (RTKs) EGFR/HER2 and inhibition of their downstream pro-survival signaling pathways. Interestingly, ATA was found to trigger oxidative and endoplasmic reticulum (ER) stresses and to activate AMP activated protein kinase (AMPK) leading to inactivation of key enzymes involved in lipid and protein biogenesis. Intraperitoneal administration of ATA significantly inhibited the growth of MDA-MB-453 xenografts in athymic mice without causing weight loss and any other side effects. Additionally, transwell migration, invasion, and wound healing assays revealed that ATA could suppress tumor angiogenesis in vitro. Taken together, our data suggest that ATA may have broad utility in the treatment of HER2-overexpressed breast cancers.