Evaluating the effects of carbon monoxide releasing molecule-2 against myocardial ischemia-reperfusion injury in ovariectomized female rats.

PURPOSE: Cardioprotective effect of carbon monoxide, a gasotransmitter against myocardial ischemia-reperfusion injury (I/R), is well established in preclinical studies with male rats. However, its ischemic tolerance in post-menopausal animals has not been examined due to functional perturbations at the cellular level. METHODS: The protective role of carbon monoxide releasing molecule-2 (CORM-2) on myocardial I/R was studied in female Wistar rats using the Langendorff apparatus. The animals were randomly divided into normal and ovariectomized (Ovx) female rats and were maintained 2 months post-surgery. Each group was further divided into 4 subgroups (n = 6/subgroup): normal, I/R, CORM-2-control (20 µmol/L), and CORM-2-I/R. The cardiac injury was estimated via myocardial infarct size, lactate dehydrogenase, and creatine kinase levels in coronary effluent and cardiac hemodynamic indices. Mitochondrial functional activity was assessed by measuring mitochondrial electron transport chain enzyme activities, swelling behavior, mitochondrial membrane potential, and oxidative stress. RESULTS: Hemodynamic indices were significantly lower in ovariectomized rat hearts than in normal rat hearts. Sixty minutes of reperfusion of ischemic heart exhibited deteriorated cardiac physiological recovery in both ovariectomized and normal groups, where prominent decline was observed in ovariectomized rat. However, preconditioning the isolated heart with CORM-2 improved hemodynamics parameters significantly in both ovariectomized and normal rat hearts challenged with I/R, but with a limited degree of protection in ovariectomized rat hearts. The protective effect of CORM-2 was further confirmed via a reduction in cardiac injury, preservation of mitochondrial enzymes, and reduction in oxidative stress in all groups. CONCLUSION: CORM-2 administration significantly attenuated myocardial I/R injury in ovariectomized rat hearts by attenuating I/R-associated mitochondrial perturbations and reducing oxidative stress.

Management of Extended-Spectrum Beta-Lactamase Urinary Tract Infections: Diagnostic and Treatment Considerations for the Older Adult.

OBJECTIVE: To review the treatment options for extended-spectrum beta-lactamase (ESBL) urinary tract infections (UTIs) in the long-term care facility setting.
DATA SOURCES: A PubMed search from January 1, 1990, through December 31, 2018, using terms "extended spectrum beta lactamase" and "urinary tract infection" was performed. Current guidelines, drug databases, and manufacturer package inserts were also used.
STUDY SELECTION: All English-language articles during the above time frame appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any articles not originally identified.
DATA SYNTHESIS: ESBL UTIs are a growing concern in the long-term care facility as these pathogens are becoming more prevalent. Patients residing in long-term care facilities have fewer treatment modalities because of medication administration and care issues. This review highlights the data on different antibiotics and their efficacy toward ESBLs in the setting of UTI.
CONCLUSIONS: Despite the challenges and limitations, there are still options for clinicians to provide optimal care, including antibiotics with different routes of administration, as well as different administration techniques. Clinicians can be successful with treating ESBL UTIs in older adults.

Pharmacokinetic Drug Interactions with Panax ginseng.

Panax ginseng is widely used as an adaptogen throughout the world. The major active constituents of P. ginseng are ginsenosides. Most naturally occurring ginsenosides are deglycosylated by colonic bacteria to intestinal metabolites. Ginsenosides along with these metabolites are widely accepted as being responsible for the pharmacologic activity and drug interaction potential of ginseng. Numerous preclinical studies have assessed the influence of various ginseng components on cytochrome P450 (CYP), glucuronidation, and drug transport activity. Results from these investigations have been largely inconclusive due to the use of different ginseng products and variations in methodology between studies. Drug interaction studies in humans have been conflicting and have largely yielded negative results or results that suggest only a weak interaction. One study using a midazolam probe found weak CYP3A induction and another using a fexofenadine probe found weak P-gp inhibition. Despite several case reports indicating a drug interaction between warfarin and P. ginseng, pharmacokinetic studies involving these agents in combination have failed to find significant pharmacokinetic or pharmacodynamic interactions. To this end, drug interactions involving P. ginseng appear to be rare; however, close clinical monitoring is still suggested for patients taking warfarin or CYP3A or P-gp substrates with narrow therapeutic indices.

Safety and tolerability of high-dose weekly liposomal amphotericin B antifungal prophylaxis.

Children with hematologic malignancies are at an increased risk of invasive fungal infections and a greater risk has been seen with exposure to building construction. Prophylaxis with high-dose (IV) liposomal amphotericin B (L-AmB) 10 mg/kg once weekly was initiated in our high risk children based on previous pharmacokinetic studies. This treatment regimen was associated with a 26% incidence of adverse infusion reactions.