Protective effects of Lithium on Sumatriptan-induced memory impairment in mice

Lithium is a drug used for the treatment of bipolar disorder. It has several mechanisms of action, and recently it is shown that lithium can antagonize the 5-HT1B/1D serotonin receptors. Sumatriptan is a 5- HT1B/1D receptor agonist used for the treatment of cluster headaches and migraine which might cause memory impairment as a potential side effect. In this study, effects of lithium on sumatriptan-induced memory impairment have been determined in a two trial recognition Y-maze and passive avoidance tests. Male mice weighing 25-30 g were divided into several groups randomly. In Y-maze test, effects of lithium (1,5,10,20,40,80 mg/kg) and sumatriptan (1,5,10 mg/kg) were assessed on memory acquisition, then lithium (0.1,1,10 mg/kg) and sumatriptan (1,10 mg/kg) were studied in passive avoidance test. Effects of lithium (1mg/kg) on sumatriptan (10 mg/kg)-induced memory impairment were studied in both of tests. The present study demonstrated that sumatriptan impaired memory in Y-maze and passive avoidance tests (P0.05), but significantly reversed sumatriptan-induced memory impairment in Y-maze and passive avoidance tests (P<0.001, P<0.05, respectively). It is concluded that lithium reverses the sumatriptan-induced memory impairment probably through 5-HT1B/1D receptors antagonism. © 2016 Tehran University of Medical Sciences. All rights reserved

Involvement of Inflammatory Cytokines in Antiarrhythmic Effects of Clofibrate in Ouabain-Induced Arrhythmia in Isolated Rat Atria

Considering the cardioprotective and anti-inflammatory properties of clofibrate, the aim of the present experiment was to investigate the involvement of local and systemic inflammatory cytokines in possible antiarrhythmic effects of clofibrate in ouabain-induced arrhythmia in rats. Rats were orally treated with clofibrate (300 mg/kg), and ouabain (0.56 mg/kg) was administered to animals intraperitoneally. After induction of anesthesia, the atria were isolated and the onset of arrhythmia and asystole was recorded. The levels of inflammatory cytokines in atria were also measured. Clofibrate significantly postponed the onset of arrhythmia and asystole when compared to control group (P � 0.05 and P � 0.01, resp.). While ouabain significantly increased the atrial beating rate in control group (P � 0.05), same treatment did not show similar effect in clofibrate-treated group (P > 0.05). Injection of ouabain significantly increased the atrial and systemic levels of all studied inflammatory cytokines (P � 0.05). Pretreatment with clofibrate could attenuate the ouabain-induced elevation of IL-6 and TNF-α in atria (P � 0.01 and P � 0.05, resp.), as well as ouabain-induced increase in IL-6 in plasma (P � 0.05). Based on our findings, clofibrate may possess antiarrhythmic properties through mitigating the local and systemic inflammatory factors including IL-6 and TNF-α. Copyright © 2016 Somayeh Moradi et al

ANTINOCICEPTIVE PROPERTIES OF HYDRO ALCOHOLIC EXTRACTS OF ANETHUM GRAVEOLENS L. (DILL) SEED AND AERIAL PARTS IN MICE

Chronic pain and its treatment have always posed a significant challenge for medical practitioners and many attempts have been made to reduce and eliminate it, both in past and recent history. Research to discover new effective drugs with excellent safety profiles is ongoing. The aim of this study was to evaluate the suitability of the plant Anethum graveolens (dill) for use as an analgesic drug. Forty-two mice were divided randomly into seven groups (n=6). In the formalin test, the first group received normal saline; the second group, extract of plant seed (300 mg/kg); the third group, extract of plant crops (300 mg/kg) and the forth group received morphine (1 mg/kg). For the hot plate test, the first group received normal saline; the second group, extract of plant seed (300 mg/kg) and the third group received extract of plant crops (300 mg/kg). All injections consisted of 0.5 ml given intraperitoneally. In the early phase of formalin test, the animals treated with seed and crop extracts did not show analgesic effects compared to control group (P=0.386, P=0.284 respectively). In contrast, in the late phase of formalin test, seed and crop extracts significantly decreased indications of pain compared to the saline group with seed extracts showing stronger analgesic effects (P=0.004, P=0.023 respectively). In the hot plate test, crop and seed extracts showed hyperalgesic properties. This effect was stronger in animals treated with crop extracts as compared to seed extracts. These findings indicate that Anethum graveolens can reduce inflammatory pain, probably by inhibiting inflammatory mediators. In contrast, this plant has no analgesic effects on spinal nociception and conversely may exacerbate it. This study provides a basis for the use of Anethum graveolens extracts in popular folk medicine, but further studies are necessary to elucidate the mechanism of its analgesic actions

POISONED BAITS: A RISING CONCERN FOR ANIMAL HEALTH

Objective: In Europe, malicious animal poisonings are nowadays of concern for both the animal and human health. Focusing on Italy, this problem has been afforded at the beginning of this century. In this frame, a law ruling-banning the preparation, possess, and employment of poisoned baits, was issued in 2001. Poisoned bait is a special threat to dogs and cats but it also kills birds of prey such as owls, kites and eagles, as well as foxes and badgers. The present study reports an overview on the different types of poisoned “hand made” baits found in 10 years of toxicological analysis. Materials & Methods: Data for this retrospective study were taken from 508 pesticide based baits analyses ranging from January 1999 to December 2009. The presence or absence of a suspected pesticide in baits was investigated by validated laboratory methods using a solid-phase or liquid-liquid extraction followed by separation and characterization by chromatographic techniques. The analyses were carried out for organophosphorus and carbamate pesticides (CI), anticoagulant rodenticides (AR), zinc phosphide (ZP), strychnine (ST) and metaldehyde (MT). In the instance the bait was not positive for the above mentioned toxics, the sample underwent screening analysis in GC-MS. Results & Conclusion: The baits found positive have been classified in 6 different: 1) baits prepared with discard or out of date food. Miscellaneous baits belong to this class and are the most frequent (n° 362, CI 52%; AR 19%; ZP 11%, ST 9%, MT 8%, other [OT] 1%). 2) laborious and original particular baits. This class groups baits that requested particular work and time in preparation, making them original (n° 85, CI 49%; AR 10%; ZP 21%, ST 2%, MT 12%, OT 4%). 3) baits containing more than one toxic substance. These baits are usually the most harmful for the animals (n° 39, CI 65%; AR 59%; ZP 20%; ST 35%; MT 12%; OT 9%). 4) baits containing non toxic material. The final intent to kill the animals is unfortunately well pursued by these baits, and for this reason this class has been inserted in the study (n° 15). 5) baits prepared with non food material. This group is seldom used (n=6, CI 50%; ST 50%), but according to officer’s reports it is a method apparently used from gypsies or other unscrupulous people to kill the guard dogs. 6) in vivo baits. This class had only a case reported

Involvement of mutation in serine 83 of quinolone resistance-determining region of gyrA gene in resistance to ciprofloxacin in Escherichia coli

Appearance of bacteria resistant to antibacterial agents puts physicians in trouble and threatens the health of the world. The rapid development of bacterial resistance in Escherichia coli to ciprofloxacin makes difficult the treatment of infectious diseases. So, detection of the locations of possible mutations in gyrase A gene (gyrA) in these mutants is very important to determine the mechanism of this resistance. In the present study, ciprofloxacin-resistant mutants were isolated from medium containing ciprofloxacin. Polymerase chain reaction (PCR) was used to amplify the gyrA gene in these mutants and DNA sequencing was used to determine the location of mutation in this gene. Results showed that the most of ciprofloxacin-resistant mutants contain mutations in quinolone resistance- determining region (QRDR) of A subunit of DNA gyrase and specially at serine 83. However, mutations outside of this region were also found at tyrosine 50 and alanine 119. In conclusion, this study confirms that mutation in serine 83 of QRDR in A subunit of DNA gyrase is the main cause of resistance to ciprofloxacin in E. coli. © 2015 by Iran University of Medical Sciences (IUMS)

MIRTAZAPINE IN BEAGLE DOGS

Objective: Mirtazapine (MRT) is a human antidepressant drug mainly metabolized by the cytochrome P450 enzyme system to 8-OH mirtazapine (8-OH) and to dimetilmirtazapine (DMR). Anecdotal clinical observations suggested doses for dogs be extrapolated from human doses, but no pharmacological studies have been reported to date to support these speculations. The aim of this study was to assess the pharmacokinetics of MRT and its metabolites DMT and 8-OH to provide useful information to improve the knowledge of this drug in canine species. Materials & Methods: The subjects were six healthy male Beagle dogs, aged from 1-2 years and weighing between 15 and 17 Kg. Animals were administered MRT (20 mg/tablet/dog) under fasting conditions. This dose was determined based on anecdotal evidence indicating an effective dose rate of about 1 mg/kg. A catheter was inserted into the right cephalic vein to withdrawal a blood sample at determined times after drug administration. Plasma MRT and metabolite concentrations were evaluated by HPLC-FL detection method re-validated in canine plasma according the following parameters: linearity, sensitivity, selectivity and accuracy. Results & Conclusion: MRT and DMR were quantified in plasma from 0.25 up to 10 h, while 8-OH was quantified from 0.50 up to 10 h. The 8-OH metabolite demonstrated the highest plasma concentration. The present study indicated that MRT has a different pharmacokinetic profile in dogs compared to that in cats and humans and caution should be paid when extrapolating doses from other species. In veterinary medicine, MRT is likely to have more applications than other drugs currently available for veterinary use, many of these are only utilised for separation anxiety disorder in dogs (clomipramine, fluoxetine and trazodone). Compared with the pharmacokinetic profiles of these drugs, MRT shows a longer mean resident time and a shorter Tmax. These properties could be beneficial in instances of accidental overdose where the expected cardio-toxic side effects and serotonin syndrome could be mitigated for this medication. The antagonism of 5-HT3 receptor by MRT may also result in an anti-emetic therapeutic effect. Its use as analgesic agent due to its effects on noradrenergic and serotonic system has been also speculated. This preliminary data could be useful in prospective studies involving MRT in canine species

Plasma zinc levels in normotensive and hypertensive adults: a comparative study in Tehran Heart Center

Background: There are conflicting reports about zinc, a trace element, in the pathogenesis of hypertension and other cardiovascular diseases. The aim of this study was to evaluate the role of zinc in high blood pressure.Methods: We conducted this study on 80 patients with primary (idiopathic) hypertension and 80 normotensive people with similar age who attended to Tehran Heart Center between 2007 and 2008. We examined the effect of zinc concentration on blood pressure in both sexes in four age groups (41-50, 51-60, 61-70 and 71-80 years old). We measured plasma zinc concentration by atomic absorption.Results: The mean plasma zinc concentrations were 0.456±0.04 µg/ml and 0.551±0.055 µg/ml in patients with hypertension and in normotensive people, respectively, (P≤0.05). Nevertheless, the mean plasma zinc concentrations were 0.494 µg/ml and 0.486 µg/ml in men with and without hypertension, respectively. The mean plasma zinc concentrations of women with and without hypertension, respectively were 0.415 µg/ml and 0.596 µg/ml, showing a significant difference between two groups (P≤0.001). Moreover, there was a significant difference in plasma zinc concentration between hypertensive and normotensive people in 51 to 60 years age group (P≤0.05), but difference were not significant between other age groups.Conclusion: The results of this study revealed the relationship between the decrease in plasma zinc concentration and increase in blood pressure in women and in the men aged 51 to 60 years

PHARMACOKINETICS OF MIRTAZAPINE AND ITS MAIN METABOLITES AFTER SINGLE ORAL ADMINISTRATION IN FASTING/FED HORSES

Mirtazapine (MRZ) is a human antidepressant drug that is metabolized, predominantly by the cytochrome P450 enzyme system, to 8-OH mirtazapine (8-OH MRZ) and dimetilmirtazapine (DMR) metabolites. In veterinary medicine, this drug is currently administered to cats and dogs with anorexia, although it could also have applications as an antidepressant, antiemetic, and analgesic agent in these species. The aim of this study was to assess the pharmacokinetics of MRZ and its metabolites DMR and 8-OH MRZ in horses. Six healthy female horses were administered MRZ (2 mg/kg) in fasting and fed states according to a balanced crossover study design. Plasma MRZ and metabolite concentrations were evaluated by high-performance liquid chromatography fluorescence detection method. Pharmacokinetic profiles of MRZ and DMR were similar (detected from 0.5 up to 34 and 48 hours, respectively), with an MRZ AUC0-N/DMR AUC0-N ratio range varying between 1.1 and 1.7. Surprisingly, 8-OH MRZ was undetected. Most of the pharmacokinetic parameters were not altered by food, with the exception of the time required to reach maximum concentration; this showed a statistical increase in subjects in the fasting state as compared with the fed state. However, because MRZ is an active substance intended for long-term administration, the slight increase of the time required to reach maximum concentration is not considered to be of any clinical consequence. In conclusion, the pharmacokinetic parameters demonstrated in this study suggest that MRZ is suitable for oral administration in the horse. However, further investigations are required to evaluate both its safety and effectiveness in this animal species