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

Cromakalim, a potassium channel opener, ameliorates the organophosphate and carbamate-induced seizure in mice

Organophosphates (OPs) and carbamates are acetylcholine esterase inhibitors (AChEIs), which can cause seizure and lethality. Anticonvulsant properties of potassium channel openers including cromakalim have been determined in previous studies. In the present experiment, the possible effect of cromakalim on the convulsion and death induced by OPs and carbamates was studied in mice. Dichlorvos (an OP, 50 mg/kg) and physostigmine (a carbamate, 2 mg/kg) were used to induce seizure in animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg was injected 30 min before dichlorvos and physostigmine, and 5 min before glibenclamide (a potassium channel blocker, 1 mg/kg) administration. All injections were performed intraperitoneally. After drugs administration, the onset of convulsion, death, the severity of seizure, and rate of mortality were investigated. Results revealed that both dichlorvos and physostigmine induced seizure activity and lethality in 100 of the animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg significantly increased the latency of both seizure and death (P<0.05). Also, cromakalim decreased the mortality rate induced by dichlorvos and physostigmine (P<0.05). On the other hand, glibenclamide blocked all aspects of the anticonvulsant effect of cromakalim (P<0.05). This study revealed for the first time that cromakalim (a KATP channel opener) diminishes the seizure and death induced by dichlorvos and physostigmine in mice, and introduces a new aspect to manage the patients who suffer from OPs/carbamates-induced seizure. © 2018 Tehran University of Medical Sciences. All rights reserved

Cromakalim, a potassium channel opener, ameliorates the organophosphate and carbamate-induced seizure in mice

Organophosphates (OPs) and carbamates are acetylcholine esterase inhibitors (AChEIs), which can cause seizure and lethality. Anticonvulsant properties of potassium channel openers including cromakalim have been determined in previous studies. In the present experiment, the possible effect of cromakalim on the convulsion and death induced by OPs and carbamates was studied in mice. Dichlorvos (an OP, 50 mg/kg) and physostigmine (a carbamate, 2 mg/kg) were used to induce seizure in animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg was injected 30 min before dichlorvos and physostigmine, and 5 min before glibenclamide (a potassium channel blocker, 1 mg/kg) administration. All injections were performed intraperitoneally. After drugs administration, the onset of convulsion, death, the severity of seizure, and rate of mortality were investigated. Results revealed that both dichlorvos and physostigmine induced seizure activity and lethality in 100 of the animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg significantly increased the latency of both seizure and death (P<0.05). Also, cromakalim decreased the mortality rate induced by dichlorvos and physostigmine (P<0.05). On the other hand, glibenclamide blocked all aspects of the anticonvulsant effect of cromakalim (P<0.05). This study revealed for the first time that cromakalim (a KATP channel opener) diminishes the seizure and death induced by dichlorvos and physostigmine in mice, and introduces a new aspect to manage the patients who suffer from OPs/carbamates-induced seizure. © 2018 Tehran University of Medical Sciences. All rights reserved

Semigroups derived from (Γ,n)-semihypergroups and T-functor

The main purpose of this paper is to introduce the concept of (Γ,n)-semihypergroups as a generalization of hypergroups, as a generalization of n-ary hypergroups and obtain an exact covariant functor between the category (Γ,n)-semihypergrous and the category semigroups. Moreover, we introduce and study complete part. Finally, we obtain some new results and some fundamental theorems in this respect

Respiratory and blood responses following intratracheal instillation of titanium dioxide nanoparticles in rabbits

Background: Nowadays, nanomaterials are used in daily life extensively. One of the most common of these materials is nano titanium dioxide (TiO2) which is used to purify the air and also sunscreens, shampoos and other hygienic products. Although nano-particles are useful, can also have potential hazards. The aim of this study is to evaluate the effects of TiO2 on lung tissue in rabbits.Methods: We divided 18 male rabbits into three groups randomly. The first group recei-ved 50 µl of TiO2 with dose of 50 mg/kg by intratracheal instillation. The second group received 50 µl of TiO2 with dose of 100 mg/kg and the third group received 50 µl of nor-mal saline by the same route. Chest X-rays were taken from all rabbits before injection and on days of 10, 17 and 24 after injection. Twenty four days after injection, rabbits anesthetized and histopathological assays, blood samples and biochemical factors were evaluated.Results: Radiographic assays showed a progressive pulmonary fibrosis in rabbits recei-ved TiO2 rather than the control group and this lesion developed to maximum at 24th day of the experiment. We also showed pulmonary emphysema and inflammation in histo-pathologycal study of groups treated with TiO2. Moreover, we observed a significant increase in the amount of liver enzymes, white blood cells and hematocrit in TiO2 treat-ed groups compared to control group (P≤0.05). There were no significant differences between plasma levels of creatinine in different groups (P>0.05).Conclusion: Results showed that nanotitanium dioxide particles can lead to pulmonary fibrosis and inflammation and also increasing liver enzymes and inflammatory cells

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)

Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effect of baclofen in mouse forced swimming test

Background Previous study confirmed that the acute treatment with baclofen by inhibition of the L-arginine-nitric oxide (NO) pathway diminished the immobility behavior in the forced swimming test (FST) of mice. Considering the involvement of NO in adenosine triphosphate (ATP)-sensitive potassium channels (KATP), in the present study we investigated the involvement of KATP channels in antidepressant-like effect of baclofen in the FST. Methods After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of the antidepressant-like activity of baclofen in mice. Baclofen at different doses (0.1, 0.3, and 1 mg/kg) and fluoxetine (20 mg/kg) were administrated by intraperitoneal (ip) route, 30 min before the FST or OFT. To clarify the probable involvement of KATP channels, after determination of sub-effective doses of glibenclamide as a KATP channel blocker and cromakalim, as an opener of these channels, they were co-administrated with the sub-effective and effective doses of baclofen, respectively. Results Baclofen at dose 1 mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20 mg/kg). Co-administration of gelibenclamide sub-effective dose (1 mg/kg) with baclofen (0.1 mg/kg) showed a synergistic antidepressant-like effect in the FST. Also, sub-effective dose of cromakalim (0.1 mg/kg) inhibited the antidepressant-like effect of baclofen (1 mg/kg) in the FST. All aforementioned treatments had not any impact on the locomotor movement of mice in OFT. Conclusions Our study for the first time revealed that antidepressant-like effect of baclofen on mice is KATP-dependent, and baclofen seems that exert this effect by blocking the KATP channels. © 201

Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, reverses endotoxin-induced impaired atrial chronotropic responsiveness to cholinergic stimulation in rats

Evidence show that endotoxemia is linked with tachycardia. The exact mechanism of tachycardia is not well-understood, but it seems that impaired cardiac chronotropic responsiveness to cholinergic stimulation plays a role in this phenomenon. The aim of this experiment was to study the effect of licofelone as a dual cyclooxygenase (COX)/5-lipoxygenase (5-LOX) inhibitor in modulation of atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats, compared with hydrocortisone and indomethacin in in vitro and in vivo studies. Rats were injected by either of lipopolysaccharide (LPS) or saline. The isolated atria were incubated with licofelone, hydrocortisone, or indomethacin in an organ bath set up. In a separate experiment, rats were injected with licofelone, hydrocortisone, or indomethacin prior to isolation of the atria. Then, in both experiments, chronotropic responsiveness to cumulative concentrations of carbacholine in organ bath was recorded. LPS injection decreased the chronotropic responsiveness to cholinergic stimulation in both in vitro and in vivo experiments, significantly (P < 0.0001), while either incubation of isolated atria with licofelone (a dual COX/5-LOX inhibitor) or injection of licofelone to animals could reverse it, completely (P < 0.01). Hydrocortisone (phospholipase A2 and COX-2 inhibitor) in vitro and in vivo (P < 0.001, P < 0.05, respectively) as well as indomethacin (COX inhibitor) in vitro and in vivo (P < 0.05, P < 0.01, respectively) exerted some lesser effects. Our data revealed that in endotoxemic rats, chronotropic hyporesponsiveness to cholinergic stimulation was modulated by the dual COX/5-LOX inhibitor licofelone, and this effect is comparable with hydrocortisone and indomethacin. © 2020 Elsevier B.V

Teratogenic effects of caffeine and clomipramine on rat fetus

Background: Obsessive-compulsive disorders and depression have a high prevalence during pregnancy therefore, pregnant women may take clomipramine and also take other drugs or consume foods that contain caffeine. As investigations about the teratogenic effects of clomipramine and its concurrent administration with caffeine during organogenesis period are scarce, we aimed to study the teratogenicity of simultaneous administration of clomipramine and caffeine in rat fetus.Methods: After dividing 42 pregnant rats to several case and control groups, we injected different doses of caffeine and clomipramine to the animals. All the injections were performed on the eighth until the 15th day of pregnancy. We removed the fetuses on the 17th day of pregnancy and studied the morphological features and apparent anomalies of the fetuses macroscopically. Results: We found a significant rate of mortality, apparent anomalies, abnormal torsion, shrinkage of skin and subcutaneous bleeding in fetuses of rats receiving high doses of caffeine or a combination of caffeine and clomipramine. Statistical analysis of the data revealed a significant increase (P?0.001) in teratogenicity of high doses of caffeine and its combination with clomipramine. Conclusion: This study implies simultaneous intake of high amounts of caffeine and clomipramine lead to teratogenicity. We recommend pregnant women to avoid uncontrolled consumption of foods that contain caffeine or drugs that contain high amounts of this substance. They should not also take clomipramine with caffeine in the first trimester of pregnancy