Amifostine is well known cytoprotector which is efficient when administered before a wide range of antineoplastic agents. The aim of our study was to investigate amifostine effects on doxorubicin-induced toxic changes in rats. Amifostine (75 mg/kg ip) was given 30 min before each dose of doxorubicin (cumulatively 20 mg/kg ip, for 28 days). The animals’ whole-body, liver, and kidney weight, serum biochemical examination, as well as microscopic examination of bone marrow, peripheral blood, liver, and kidney, were done on day 56 of the study. Hepatic and renal alterations were carefully quantified by semiquantitative grading scales—hepatic and renal damage score, respectively. In amifostine-pretreated rats, the number of peripheral blood leukocytes was significantly higher in comparison to doxorubicin-only treated group, preferentially protecting neutrophils. In the same group of rats, hepatic and renal alterations associated with polymorphonuclear cell infiltrates were significantly less severe than those observed in animals receiving only doxorubicin. Our results showed that amifostine successfully protected rats against multiple-dose doxorubicin-induced toxicity by complex, and still not fully elucidated mechanisms of action.

Background and Objectives: The purpose of the study was to determine the prevalence rate of potentially inappropriate prescribing (PIP), by using the Screening Tool of Older Person’s potentially inappropriate Prescriptions (STOPP) criteria in older outpatients, and its association with potential clinically significant drug–drug interactions (csDDIs). Materials and Methods: A cross-sectional study included 248 outpatients ≥65 years old divided into two groups depending on the presence of csDDIs. For estimating the clinical significance of csDDIs we used Medscape′s "Drug Interaction Checker". We applied the thirty PIP indicators from the STOPP criteria. Results: The presence of PIP (25.00%; all patients) was significantly higher in the group with potential csDDIs compared to the other group (43 vs. 19, respectively; Chi-square test, χ² = 9.947; p < 0.01). The most common PIP included the inappropriate use of proton pump inhibitors, long acting benzodiazepines, usage of thiazide diuretic in patients with gout, and duplication of therapeutic class. Patients with potential csDDIs had 43 potentially inappropriate medications (PIMs) prescribed. Out of this number, 12 (27.91%) PIMs were identified to participate in potential csDDIs. There was a correlation between the number of medications prescribed and the number of PIMs (ρ = 0.297; p < 0.01) and between the number of PIPs and the number of potential csDDIs (ρ = 0.170; p < 0.01). Conclusions: Older outpatients with potential csDDIs in relation to those with no potential csDDIs had significantly more prescribed drugs in total as well as inappropriate drugs. Almost 30% of these PIMs were included in potential csDDIs.

The present study was done to investigate and compare the effect of acetylcholinesterase inhibitor, physostigmine (0.030, 0.045, 0.060 and 0.075 mg/kg sc) and Ca-antagonist, verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg sc) on open field behavior in male Wistar rats with bilateral electrolytic lesions of nucleus basalis magnocellularis (NBM). NBM-lesions produced a significant increase and decrease of ambulation and number of inner squares entered, and defecation, respectively, with no influence on grooming in rats exposed to novel environment. Physostigmine and verapamil in all tested doses, given 30 min before the test did not affect the open field behavior in control animals. In contrast to that, physostigmine (0.045, 0.060 and 0.075 mg/kg) and verapamil (2.5 and 5.0 mg/kg) significantly reduced ambulation and number of inner squares entered in NBM-lesioned rats. Also, physostigmine in a dose of 0.060 mg/kg significantly decreased defecation and in doses of 0.060 and 0.075 mg/kg the grooming, as well. On the other hand, verapamil only in a dose of 2.5 mg/kg significantly increased defecation. It could be concluded that lesions of NBM in rats induced disturbances in the open field behavior, which might be successfully ameliorate by physostigmine and verapamil treatment.

Background/Aim. Diclofenac, a non-selective inhibitor of cyclooxygenase, with analgesic, anti-inflammatory and antipyretic effects, is one of the most prescribed nonsteroidal anti-inflammatory drugs (NSAIDs). The aim of the study was to analyse prescribing patterns of diclofenac systemic formulations at the outpatient care settings (OCS) in Montenegro, in patients with cardiovascular (CV) disease (CVD) and patients with risk factors for CVD, during the period 2016-2020. Methods. The retrospective, national, drug utilisation study, included patients with CVD, to whom prescribing of diclofenac is contraindicated and patients with risk factors for CVD, for which diclofenac can be prescribed, but with increased precaution. Primary health care information system (PHCIS) has been used as source of medical data for these patients. Results. Within the observed period, prescribing and consumption of diclofenac systemic formulations, dominantly oral formulations in 75 mg dose, increased by 36.9 % (from 4.6 of defined daily doses (DDD) /1,000 inhabitants/day in 2016 to 6.3 DDD/1,000 inhabitants/day in 2020). The rising trend in prescribing diclofenac was also noted in patients with CVD/ risk factors for CVD, for which diclofenac prescribing is contraindicated/precautioned. Out of the overall number of patients who were prescribed diclofenac in 2016, 2017, 2018, 2019 and 2020, 16%, 18%, 24%, 15% and 20% of them, respectively, had a CVD/ risk factor for CVD. The highest number of CV patients (39.7%), who were contraindicated for prescribing of diclofenac, had ischemic heart disease (they had been prescribed 40.7% DDD/1,000 inhabitants/day of diclofenac of overall prescribed medicine for this group of patients). The highest number (77.4%) of patients who could be prescribed the drug, but with increased precautions, had hypertension and they were prescribed in 77.2% of DDD/1,000 inhabitants/day of diclofenac of overall prescribed drug for this group of patients. Conclusion. Despite undertaken regulatory measures aimed at safer prescription of diclofenac to patients with CVD or risk factors for CVD, this medicine is still widely prescribed, even in cases representing contraindications for its use.