The effect of early and long-term propranolol therapy on learning and memory in mice.

Propranolol is the treatment of choice for infantile hemangioma. We investigated the effects of long-term propranolol use in early infancy on learning and memory later in life in mice. At three weeks of age, mice were randomly divided into six experimental groups. Groups 1 and 2 (controls) received only saline for 21 days. Groups 3 and 4 received propranolol (2.5 mg/kg) for 21 days. Groups 5 and 6 received propranolol (5 mg/kg) for 21 days. Groups 1, 3 and 5 were tested at the end of 21 days of treatment (week 6). However, groups 2, 4 and 6 received a 2-week break and then (week 8) exposed to tests. In the Morris water maze test, propranolol (2.5 and 5 mg/kg) dose-dependently increased the time spent in the target quadrant in mice at weeks 6 and 8. However, propranolol did not affect the swimming speed in both time periods. There were no significant effects of propranolol on the number of errors evaluated during the radial arm maze tests. In conclusion, long-term use of propranolol in early infancy did not disrupt the learning and memory of mice.

Effects of long-term treatment with haloperidol, clozapine and aripiprazole on mice isolated vas deferens.

PURPOSE: Sexual dysfunction is a common condition in patients taking antipsychotics and is the most bothersome symptom and adverse drug effect, resulting in a negative effect on treatment compliance. Pharmacology research into human ejeculatory disorders is limited to clinical studies with registered drugs affecting the ejaculation process; therefore, animal research has become the need. We aimed to investigate the effects of haloperidol, clozapine and aripiprazole on serotonin, noradrenaline, adenosine triphosphate (ATP) and potassium chloride (KCl)-induced contractions of the vas deferens in order to evaluate the effect of haloperidol, clozapine and aripiprazole on the contraction of the vas deferens. METHODS: Male inbred BALB/c ByJ mice aged 7 weeks upon arrival to the laboratory were used in this study. Haloperidol, clozapine, aripiprazole, serotonin, noradrenaline, ATP and KCl were dissolved in 0.9% physiological saline. The mice were randomly divided into experimental groups as follows: saline; haloperidol 0.125 mg/kg; haloperidol 0.25 mg/kg; clozapine 1.25 mg/kg; clozapine 2.5 mg/kg; aripiprazole 3 mg/kg; aripiprazole 6 mg/kg. Mice were treated by ip injection of drugs during 21 days. Mice receiving only the vehicle ip (0.9% saline) during 21 days served as control group (n = 7). Each experimental group consisted of 7 mice. After 21 days of treatment, epididymal and prostatic portions of vas deferens were surgically dissected free and immersed in 20-mL organ baths containing Krebs' solution. The effects of chronic treatment with haloperidol (0.125 and 0.25 mg/kg), clozapine(1.25 and 2.5 mg/kg) and aripiprazole (3 and 6 mg/kg) were investigated on serotonin [10 (-8) to 10 (-4) M], noradrenaline [10 (-8) to 10 (-4) M], ATP [10 (-8) to 10 (-4) M] and 80 mM KCl-induced contractile responses in the epididymal and prostatic portions of mice isolated vas deferens strips. Statistical comparison between the groups was performed using ANOVA supported by Dunnett's post hoc test. RESULTS: Serotonin-induced contractile responses were significantly increased in the epididymal and prostatic portions of the vas deferens obtained from the haloperidol-treated group and clozapine-treated group. However, aripiprazole treatment had no effect on serotonin responses in both epididymal and prostatic portions of mice vas deferens. On the other hand, haloperidol and clozapine treatments significantly inhibited both noradrenaline and ATP-induced contractions of the prostatic and epididymal portions of the mice vas deferens, but had no effect on KCl-induced contractions of the vas deferens in both portions. There were no significant differences in KCl-induced contractile responses among the groups. CONCLUSIONS: These results revealed that induced contractions of vas deferens were affected after chronic treatment with haloperidol and clozapine but not aripiprazole. Serotonergic, noradrenergic and purinergic receptors may, at least in part, contribute to changes in vas deferens contractions in mice with chronic treatment of haloperidol and clozapine but not aripiprazole.

The effects of povidone iodine (pH 4.2) on patients with adenoviral conjunctivitis.

OBJECTIVE: To compare the efficacy of classical treatment and povidone-iodine treatment for adenoviral conjunctivitis. METHODS: This retrospective study was conducted at the Centre of Marmara Eye Health, Sakarya, Turkey, between January 2011 and February 2014, and comprised adult patients suffering from adenoviral conjunctivitis. The participants were randomly divided into two groups. Group I was given povidone-iodine solution while Group II was given the classical treatment and was taken as control. Povidone-iodine treatment was administered as three drops three times per day. The classical treatment comprised three drops of trifluorothymidine three times per day. Treatment were continued for two weeks. The patients who had not recovered in this time frame were defined as 'late recovering' patients. SPSS 23 was used for data analysis. RESULTS: Of the 112 participants, there were 56(50%) in each group. In Group I, 54(96.4%) patients recovered in two weeks, while 2(3.6%) took more time. In Group II, 33(58.9%) patients recovered in two weeks while 23(41.1%) took more time (p<0.001). Overall, 92(82.1%) patients had familial transmission-contamination. CONCLUSIONS: A new treatment protocol of povidone-iodine was used safely in patients with adenoviral conjunctivitis. Familial transmission was found very important to adenoviral conjunctivitis infection.

Effects of chronic administration of adipokinetic and hypertrehalosemic hormone on animal behavior, BDNF, and CREB expression in the hippocampus and neurogenesis in mice.

Neurosecretory cells in corpus cardiacum of insects synthesize a set of hormones that are called adipokinetic, hypertrehalosaemic or hyperprolinaemic, depending on insect in question. This study investigated effects of chronic administration of Anax imperator adipokinetic hormone (Ani-AKH), Libellula auripennis adipokinetic hormone (Lia-AKH), and Phormia-Terra hypertrehalosaemic hormone (Pht-HrTH) on depression, anxiety, analgesy, locomotion in forced swimming (FST), elevated plus-maze (EPM), hot plate, and locomotor activity tests. Ani-AKH (1 and 2 mg/kg), Lia-AKH (1 and 2 mg/kg), and Pht-HrTH (1 and 2 mg/kg) had antidepressant effects in forced swimming test. Lia-AKH (2 mg/kg) and Pht-HrTH (1 and 2 mg/kg) had anxiolytic effects when given chronically in elevated plus-maze test. Ani-AKH (1 and 2 mg/kg) and Pht-HrTH (2 mg/kg) had antinociceptive effects in hot plate test in male balb-c mice. Ani-AKH (2 mg/kg), Lia-AKH (1 and 2 mg/kg), and Pht-HrTH had locomotion-enhancing effects in locomotor activity test in male balb-c mice. Drug treatment significantly increased brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) gene expression levels compared to control levels. Pht-HrTH and Ani-AKH groups had significantly increased numbers of BrdU-labeled cells, while neurodegeneration was lower in the Pht-HrTH group. Our study showed that AKH/RPCH family peptides may be used in treatment of psychiatric illness such as depression and anxiety, in treatment of pain and in diseases related to locomotion system. AKH/RPCH family peptides increase neurotrophic factors in brain and have potential proliferative and neuroprotective effects in hippocampal neurogenesis and neurodegeneration.

An Overview of the Orphan Medicines Market in Turkey.

BACKGROUND: The health policies of many countries and regions have already defined orphan drugs for rare diseases. Although there is no official definition of orphan drugs in Turkey, all orphan drugs are covered by reimbursement, regardless of their market authorization status. Thus, a pharmacoeconomic analysis does not have to be presented to the Social Security Institution (Sosyal Güvenlik Kurumu) for reimbursement decisions on orphan drugs. OBJECTIVE: The aim of this study was to shed light on the use of orphan drugs to aid classifications of rare diseases and assessments of orphan drugs in Turkey. METHODS: Data for sales of authorized orphan drugs and all other drugs were extracted from the IMS Turkey for 2008, 2009, and 2010. Nonauthorized orphan drug sales data were extracted from records of the Turkish Pharmacists' Association for the same years. Government prices were obtained from the Sosyal Güvenlik Kurumu. RESULTS: The European Medicines Agency has classified more than 60 orphan drugs for rare diseases. Of these, 50 entered the Turkish market in recent years, half of which were authorized. The remaining drugs were imported through the early access procedure. Antineoplastic agents accounted for the largest percentage of orphan drugs, with 58% of the total market share. In 2010, there were 18 such agents in use, at a cost of €120 million. CONCLUSIONS: Although legislation is not yet in place for orphan drugs in Turkey, recognized pricing and reimbursement policies are in operation. This situation facilitates an analysis of orphan drug prices and reimbursement policies in Turkey.

Opioids for cancer pain: availability, accessibility, and regulatory barriers in Turkey and Pallia-Turk Project.

Palliative care is an emerging topic in Turkey within recent years. Currently, there are only few number of palliative care services across the country and majority of the centers are pain control units. Morphine consumption rate per capita is low, accessibility and availability of morphine products are also limited. One of the main headings of Turkish Cancer Control Programme 2009-2015 is palliative care and a serial palliative care unit implementation with continuous training programmes is planned to be finalized until 2015. This article reviews the current palliative care situation in Turkey, opioid availability in Turkey and also briefly summarizes Pallia-Turk Project which is unique with respect to many different aspects for implementation, and can be a good model for many other countries that still did not have such an implemented palliative care program.