No abstract

Silica powders consisting of small spherical particles (50-200 nm) have been obtained by the sol-gel method. A suspension of such particles in the Krebs-Hanseleit solution has been introduced into the coronary circulation of a beating perfused rat heart. The influence of the suspension on the heart muscle and the coronary vessels in the rat body has been histopathologically examined. The particles have not left the lumen of the vessels and have not caused any side effects. These observations suggest the possibility of using such silica particles as a carrier for selected drugs.

hibitors, androgen deprivation therapy, heparin, calcineurin inhibitors and some chemotherapies are among the drugs increasing the risk of osteoporotic fractures [1].The mechanisms of the regulation of bone turnover involved in the etiology and pathology of osteoporosis seem to be very complex. Recent papers have revealed that various nuclear receptors are involved in the regulation of bone metabolism, its physiology and pathology. Many studies suggest Osteoporosis is defined as pathological bone microarchitecture making bones prone to low-energy fractures. In recent decades it has become one of the major health and socio-economic problems in many countries. Drug-induced osteoporosis is a significant health problem, as many drugs have deleterious effects on bone metabolism. Glucocorticoids, proton pump inhibitors, selective serotonin receptor inhibitors, thiazolidinediones, anticonvulsants, medroxyprogesterone acetate, aromatase in- AbstractBackground. Drug-induced osteoporosis is a significant health problem, as many drugs have deleterious effects on bone metabolism. Data from several studies concerning the influence of retinol on bone homeostasis are inconsistent. Objectives. The purpose of this study was to investigate the influence of tazarotene, a selective agonist of the retinoic acid receptor (RAR), on bone metabolism and bone mechanical properties in rats. Material and Methods. Sixteen male Wistar rats were assigned either to the group receiving tazarotene or to the control group. Serum biochemical markers of bone turnover (osteocalcin: OC, tartrate resistant acid phosphatase 5: TRACP5b, and osteoprotegerin: OPG) and the mechanical properties of bones were analyzed. Results. The mean Young's modulus was 24% higher (p < 0.05) in the control group than in the group receiving tazarotene. The stiffness of femur bones was 25% lower (p < 0.05) in rats receiving tazarotene. Flexural yield stress was slightly (2%) decreased in the tazarotene group, but the difference was not statistically significant. In the tazarotene group significantly lower serum concentration of bone turnover markers were obeserved (TRACP5b: 0.86 ± 0.30 ng/mL vs. 2.17 ± 0.67 ng/mL, OC: 7.77 ± 2.28 ng/mL vs. 13.04 ± 3.54 ng/mL and OPG: 0.09 ± 0.04 ng/mL vs. 0.27 ± 0.10) than in the control group. Conclusions. Tazarotene worsened bone mechanical properties and inhibited bone turnover in rats. These results suggest that tazarotene has a negative impact on bone metabolism and that it exerts osteoporotic activity (Adv Clin Exp Med 2016, 25, 2, 213-218).

Purpose: The aim of the study was to investigate the effect of sertraline on the rat heart during ischemia and reperfusion and to determine its effect on NO production. Materials and methods: The study was performed on isolated rat hearts. Hearts from three groups were perfused with sertraline at three different concentrations and subjected to global ischemia and reperfusion. Hearts from the other three groups were perfused with the same concentrations of sertraline but without the ischemia/reperfusion process. Two control groups were perfused with the Krebs-Henseleit solution only with and without ischemia/reperfusion process. Coronary flow (CF), heart rate (HR), left ventricular developed pressure (LVDP) and maximum rate of rise of left ventricular pressure (dP/dt max) were measured. Perfusate effluent was collected to determine creatine phosphokinase (CPK) and nitrate plus nitrite (NOx) levels. Results: In non-ischemic groups, sertraline at the concentration of 10 μmol/L exerts a strong vasodilatory effect on CF, and after a short positive inotropic effect, it exerts a strong inotropic and chronotropic negative effect on isolated rat hearts and causes a direct damage to cardiomyocytes. At the concentration of 1 μmol/L, sertraline exerts an increasing negative inotropic effect. There were no hemodynamic differences between any of groups of hearts subjected to reperfusion. Sertraline had no effect on the nitric oxide concentration in coronary effluent neither in rat hearts subjected to ischemia/reperfusion nor in nonischemic conditions. Conclusion: Sertraline at dose 10 μmol/L exerts a strong vasodilatory effect on coronary flow, and after a short positive inotropic effect, it exerts a strong negative effect on isolated rat hearts, causing a direct damage to cardiomyocytes. Sertraline had no effect on the nitric oxide concentration in coronary effluent.

The aim of the study was to assess the effect of the prolonged intake of three b-blocking drugs (propranolol, metoprolol and nebivolol) on the sexual behavior and penile microcirculation of rabbits. Drugs were administered p.o. for 9 weeks and every three weeks in each group (n ¼ 13) one subgroup (n ¼ 7) performed behavioral tests, whereas in the second subgroup (n ¼ 6) penile microcirculation was measured with a laser Doppler flowmeter. The copulation studies revealed significant impairment of sexual function only in the propranolol treated group. The measured behavioral parameters suggest that at a given dose propranolol affects more performance rather than arousal aspects of rabbits' sexual behavior. In the course of the whole study no significant difference was observed among groups in penile blood flow. The data indicate that among the b-blockers given only propranolol interferes with sexual behavior, and that b-blockers do not appear to have a negative effect on penile microcirculation.

Chronic diseases often require long-lasting pharmacotherapy. Administration of some medicines on a daily routine may cause troublesome adverse effects thus discouraging the patient from further treatment. An abrupt withdrawal of formerly continuous pharmacotherapy not proceeded by the professional medical consultation may endanger the patient either due to the relapse of the disease or the onset of withdrawal symptoms that, despite some opinions, are not limited only to potentially addictive medications. These symptoms may be mistaken for a clinical manifestation of a yet another medical condition of the ill leading to a vicious cycle of repeated diagnostics – additional pharmacotherapy – discontinuation of treatment due to drug intolerance – novel symptoms – repeated diagnostics etc., especially in the elderly. Unfortunately, even some medical doctors tend to forget that administration of specific drugs should not be stopped suddenly because certain withdrawal symptoms are more harmful than mild drug-induced adverse reactions. On the other hand, this is the clinician’s individual decision whether to stop or to continue the treatment in the presence of drug intolerance reported by the patient as many “practical” guidelines either do not give any recommendations or the statements are too general to be helpful in every-day practice. Therefore, the authors review the data on the causative factors and clinical implications of a sudden drug withdrawal, including mainly stricte non-addictive medicines in use for diseases of high incidence in general population.

Chronic diseases often require long-lasting pharmacotherapy. Administration of some medicines on a daily routine may cause troublesome adverse effects thus discouraging the patient from further treatment. An abrupt withdrawal of formerly continuous pharmacotherapy not proceeded by the professional medical consultation may endanger the patient either due to the relapse of the disease or the onset of withdrawal symptoms that, despite some opinions, are not limited only to potentially addictive medications. These symptoms may be mistaken for a clinical manifestation of a yet another medical condition of the ill leading to a vicious cycle of repeated diagnostics – additional pharmacotherapy – discontinuation of treatment due to drug intolerance – novel symptoms – repeated diagnostics etc., especially in the elderly. Unfortunately, even some medical doctors tend to forget that administration of specific drugs should not be stopped suddenly because certain withdrawal symptoms are more harmful than mild drug-induced adverse reactions. On the other hand, this is the clinician’s individual decision whether to stop or to continue the treatment in the presence of drug intolerance reported by the patient as many “practical” guidelines either do not give any recommendations or the statements are too general to be helpful in every-day practice. Therefore, the authors review the data on the causative factors and clinical implications of a sudden drug withdrawal, including mainly stricte non-addictive medicines in use for diseases of high incidence in general population. Gastric acid blockers, benzodiazepines, some antidepressants and opioid analgetics have been described in the review.