Assessment of the potential interactions between favipiravir and radiocontrast agents.

BACKGROUND: In cases of coronavirus disease 2019 (COVID-19), favipiravir is commonly included to the therapy regimen. Drug interactions between favipiravir and other COVID-19 therapy drugs are frequently researched. However, no research on possible drug interactions between Favipiravir and radiocontrast agents, which have become almost crucial in diagnostic processes while not being part of the treatment, has been found. AIM: To determine potential medication interactions between Favipiravir and radiocontrast agents. METHODS: The study comprised patients who were taking Favipiravir for COVID-19 therapy and underwent a contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) test while taking the medicine. The computerized patient files of the cases included in the study, as well as the pharmacovigilance forms in the designated hospital, were evaluated for this purpose. RESULTS: The study included the evaluation of data from 1046 patients. The study sample's mean age was 47.23 ± 9.48 years. The mean age of cases with drug interactions was statistically significant greater than that of cases with no drug interactions (P = 0.003). When evaluated with logistic regression analysis, a 1-year raises in age increases the risk of developing drug interactions by 1.63 times (P = 0.023). There was no statistically significant difference in the occurrence of medication interactions between the sexes (P = 0.090). Possible medication interactions were discovered in 42 cases (4%). CONCLUSION: The findings of this study revealed that the most notable findings as a result of the combined use of contrast agents and favipiravir were increased creatinine and transaminase values, as well as an increase in the frequency of nausea and vomiting. The majority of drug interactions discovered were modest enough that they were not reflected in the clinic. Drug interactions become more common as people get older.

Profile of psychotropic agents used in autism spectrum disorder according to comorbidities in Turkey: A 4-year evaluation.

It is known that the use of psychotropic pharmaceuticals is common in comorbidities seen in autism spectrum disorder (ASD). We have very limited knowledge about which psychotropic drugs are prescribed when comorbidities are diagnosed in patients with ASD. It is aimed to determine the profile of psychotropic agents in patients diagnosed with ASD associated with comorbidities between the ages of 0-24 in Turkey over 4 years. Data belonging to ASD in Prescription Information System (PIS) was obtained from the 'Turkish Medicines and Medical Devices Agency'. A total of 34 066 prescriptions including 45 624 psychotropic drugs were analyzed. A total of psychotropic drugs prescribed for patients with ASD was 75.4%. The following psychotropic drugs were prescribed for the patients with ASD and its comorbidities; risperidone (28.6%), aripiprazole (13.7%), and valproic acid (11.3%) are the most preferred psychotropics. The percentage of pharmaceuticals containing psychotropic active substances in prescriptions with ASD and its comorbidities is 7.5%. This study is the first research in which psychotropics used in ASD were evaluated over a wide period and nationwide. Antipsychotics were most commonly prescribed with the diagnosis of ASD. In the presence of ASD and its comorbidities, risperidone was most frequently prescribed.

Role of natural products and intestinal flora on type 2 diabetes mellitus treatment.

Diabetes mellitus (DM) is a complicated, globally expanding disease that is influenced by hereditary and environmental variables. Changes in modern society's food choices, physical inactivity, and obesity are significant factors in the development of type 2 DM (T2DM). The association between changes in intestinal flora and numerous disorders, including obesity, diabetes, and cardiovascular diseases, has been studied in recent years. The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients' intestinal flora, as well as their therapeutic choices. Also included is a summary of the anti-diabetic benefits of natural compounds demonstrated by studies. The short-chain fatty acids theory, the bile acid theory, and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM. Due to an intestinal flora imbalance, abnormalities in short-chain fatty acids and secondary bile acids have been found in diabetic patients. Additionally, metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation. The agenda for diabetes treatment includes the use of short-chain fatty acids, probiotics, prebiotics in the diet, fecal bacteria transplantation, and antibiotics. Animal studies have proven the antidiabetic benefits of numerous bioactive substances, including Flavonoids, Alkaloids, Saponin, and Allicin. However, further research is required to contribute to the treatment of diabetes.

Possible agent for COVID-19 treatment: Rifampicin.

Rifampicin is a promising drug for the treatment of coronavirus disease 2019 based on its antiviral properties and recent in silico studies. In silico studies can serve as a foundation for further studies.

Do Anxiety and Depression Levels Affect the Inflammation Response in Patients Hospitalized for COVID-19.

OBJECTIVE: The whole world is still struggling with the COVID-19 pandemic. Inflammation response, thought to be associated with severe illness and death, is an important research topic in COVID-19. Inflammation is also an essential condition explored in psychiatric illnesses. Our knowledge about the relationship between the inflammation response and psychiatric comorbidities in patients with COVID-19 is very limited. In this study, the relationship between anxiety and depression levels and inflammation response of patients with COVID-19 hospitalized in the hospital was examined. METHODS: 175 patients were included in the study. Sociodemographic Data Form, Beck Depression Inventory and Beck Anxiety Inventory were applied to the patients. To evaluate the inflammation responses, blood sedimentation rate, C-reactive protein (CRP), procalcitonin, ferritin, neutrophil/lymphocyte ratio (NLR), and IL-6 levels were examined. RESULTS: In our study, no relationship was found between anxiety and depression levels and inflammatory responses in patients hospitalized with a diagnosis of COVID-19. Anxiety and depression levels of women were higher than men, and NLR, ferritin, IL-6 levels were found to be lower than men. Anxiety levels increase with age. There is a positive correlation between NLR and ferritin levels and duration of hospitalization. CONCLUSION: Our study examining the relationship of psychiatric comorbidities with the inflammation response and our increasing literature knowledge, together with studies evaluating the mental effects of COVID-19, suggest that determining the relationship between inflammation responses and psychiatric comorbidities in COVID-19, whose pathophysiology has not been clarified yet, maybe an essential step in interventions on the course of the disease.

Investigation of the Possible Protective Effects of Ketamine and Dantrolene on the Hippocampal Apoptosis and Spatial Learning in Rats Exposed to Repeated Electroconvulsive Seizures as a Model of Status Epilepticus.

AIM: To evaluate the possible neuroprotective effects of ketamine and dantrolene on the hippocampal apoptosis and spatial learning in rats exposed to repeated electroconvulsive seizures (ECS) as a model of status epilepticus (SE). MATERIAL AND METHODS: Twenty-four rats were assigned to 4 groups. 1st Group was Sham. 2nd Group was ECS: ECS was induced by ear electrodes via electrical stimulation. The same ECS protocol was applied to the 3th and 4th Groups which received ketamine (40 mg/kg s.c.) or dantrolene (5 mg/kg i.p.) 1 h before each ECS, respectively. Following 30 days of recovery, the cognitive status of the animals was evaluated via Morris Water Maze (MWM). The same experimental protocol was repeated 14 days afterward to evaluate the retention of the memory. Hippocampal apoptosis was examined in corresponding experimental groups. RESULTS: All the animals in four groups learned the task with no significant difference between groups in MWM. The ECS+ketamine group showed memory impairment 14 days afterward. ECS+dantrolene group was not different from controls. ECS caused long term apoptotic processes in dentate gyrus (DG) and non-apoptotic neuronal injury in CA1 and CA2. CONCLUSION: Dantrolene and ketamine inhibited apoptosis and showed neuroprotective effects. Although ketamine and dantrolene inhibited ECS-induced apoptosis and non-apoptotic injury, they did not produce similar effects on memory retention. It will be warranted to evaluate cognitive dysfunction by taking into consideration the other factors in addition to apoptosis and neurodegenerative changes.

The Effects of Minocycline on the Hippocampus in Lithium- Pilocarpine Induced Status Epilepticus in Rat: Relations with Microglial/Astrocytic Activation and Serum S100B Level.

AIM: To investigate possible correlations between serum S100B levels and microglial/astrocytic activation in status epilepticus (SE) in lithium-pilocarpine-exposed rat hippocampi and whether serum S100B levels linearly reflect neuroinflammation. Additionally, to assess the effects of minocycline (M), an inhibitor of neuroinflammation. MATERIAL AND METHODS: Rats were divided into 4 groups (6/group), namely, control (C), sham, SE, and SE+M. Animals were exposed to lithium-pilocarpine to induce SE in the SE and SE+M groups. Cardiac blood was collected to measure S100B levels, and coronal brain sections including the hippocampus were prepared to examine microglial/astrocytic activation and to evaluate neuroinflammation at day 7 of SE. RESULTS: Serum S100B levels, OX42 (+) microglia in CA1, and GFAP (+) astrocytes in both CA1 and dentate gyrus (DG) were higher in the SE+M group than in the C group. Most importantly, highly positive correlations were found between S100B levels and microglial activation in CA1, apart from astrocytic activation in CA1 and DG. Unexpectedly, microglial activation in CA1 and astrocytic activation in DG were also enhanced in the SE+M group compared with the C group. Moreover, M administration reversed the neuronal loss observed in DG during SE. CONCLUSION: These results suggest that serum S100B is a candidate biomarker for monitoring neuroinflammation and that it may also help predict diagnosis and prognosis.

The effects of melatonin on intestinal adaptation in a rat model of short bowel syndrome.

INTRODUCTION: Short bowel syndrome (SBS) is a clinical condition resulting from the loss of absorptive surface area following resection of 50% or more small bowel. Morphological and functional changes called "intestinal adaptation" occur in the residual intestine. Melatonin exists in the gastrointestinal tract and has effect on mitotic activity. Therefore, we hypothesized that melatonin may have beneficial effects on intestinal adaptation. MATERIALS AND METHODS: A total of 32 male Wistar albino male rats were divided into four groups. In group I (sham-S), small bowel was transected and reanastomosed. In group II (SBS-control), 75% small bowel resection and anastomosis were performed. In group III (SBS-vehicle), after 75% small bowel resection and anastomosis, 2 mL of 5% ethanol in saline was given intraperitoneally once a day. In group IV (SBS-melatonin), after 75% small bowel resection and anastomosis, 300 µg/kg melatonin was given intraperitoneally once a day. After 15 days, small bowels were removed and divided into two segments as jejunum and ileum. Each segment was weight and measured. Histological examination was performed in all samples. Bowel and mucosal weights and DNA/protein ratio were calculated. Apoptotic cells were also identified. RESULTS: The bowel length measurements were statistically longer in group IV. Mucosal and bowel weights were the highest in group IV. The villus height, crypt depth, and the number of mitotic figures were the highest in the jejunum of group IV. Melatonin also gave rise to a significant increase in DNA/protein ratios in group IV. CONCLUSION: According to this study, melatonin significantly enhanced intestinal adaptation.

Effect of a chloride channel inhibitor, 5-nitro-2- (3-phenylpropylamino)-benzoate, on endothelin-1 induced vasoconstriction in rabbit basilar artery.

AIM: Endothelin-1 (ET-1) has been implicated in the pathophysiology of cerebral vasospasm. Chloride (Cl-) channels exist in vascular smooth muscle and activation of these channels leads to depolarization and contraction. The aim of the present study was to test the effect of 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), a Cl- channel antagonist, on the ET-1-induced cerebral vasospasm in rabbit basilar artery and thus investigate the contribution of Cl- channels. MATERIAL AND METHODS: Thirty rabbits were divided into five groups and received intra-arterial injection of isotonic saline (Group I, n=6), ET-1 (group II, n=6), ET-1 plus NPPB (Group III, n=6), dimethylsulfate (DMSO4) (Group IV, n = 6) and NPPB (Group V, n=6). Pre and post injection basilar artery diameters were measured in each group and transmission electron microscopic investigations on basilar arteries were performed. RESULTS: The mean pre-injection and post-injection vessel diameters were 0.8833 mm and 0.7000 mm in ET-1 group, 0.6833 mm and 0.8500 mm in ET-1 + NPPB group. NPPB administered prior to ET-1 injection, prevented the ET-1-induced vasoconstriction. Additionally, NPPB prevents the ET-1 induced changes in vessel wall and neurons in the brain stem. CONCLUSION: The results of this study add further insights to our armamentarium against cerebral vasospasm.

The effects of iloprost, a prostacyclin analogue, in experimental ischaemia/reperfusion injury in rat ovaries.

Ovarian torsion is a surgical emergency affecting not only the ipsilateral ovary but also contralateral ovary. Although the conventional treatment is salpingo-oophorectomy, recent studies advocate detorsion. We hypothesized that iloprost, an analogue of prostacyclin with cytoprotective properties, may prevent the harmful effects of ischaemia-reperfusion injury in bilateral ovaries after unilateral ovarian torsion-detorsion in rat. In this study, 24 female Wistar-albino female rats were divided into four groups. Ovarian torsion was produced by applying vascular clamps to right ovaries. In Group I, bilateral oophorectomy was performed. In group II, bilateral oophorectomy was performed after a unilateral torsion period of 4h. In group III, bilateral ovaries were removed, following unilateral torsion-detorsion periods each lasted for 4h. Saline was injected i.p. 30 min before detorsion. In group IV, same experimental protocol, which was conducted in group III, was repeated. Iloprost was injected i.p. 30 min before detorsion instead of saline in group IV. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), which are the indicators for oxidative stress were determined and histopathological evaluation was performed in bilateral ovaries in all groups. The MDA and NO levels for ipsilateral ovaries of four groups were compared and no significant difference was found (p>0.05). The same comparison were done for the contralateral sides and no difference was seen either (p>0.05). In histological examination, iloprost produced improvement in I/R-induced alterations in ipsilateral and contralateral ovaries. In conclusion, these results showed that iloprost has beneficial effect on the histological appearances in both the ipsilateral and contralateral rat ovaries after unilateral torsion-detorsion.

Nicotine potentiates the electrical field stimulation-evoked contraction of non-pregnant rabbit myometrium.

The women who smoke have lower fertility rates which might be due to harmful effects of nicotine on tubal function and menstrual cycle. Although the uterine contractility of the non-pregnant uterus plays an important role in the human reproduction process, the influence of nicotine on the contractile responses in uterus is not known. Nicotine increases the release of neurotransmitters following nerve stimulation both in the central and peripheral nervous system through acting on nicotinic acetylcholine receptors (nAchRs). The aim of this study was to examine whether the electrical field stimulation (EFS)-evoked contraction is altered in rabbit myometrium strips in the presence of nicotine to evaluate the changes in contractility. EFS-evoked contractile responses were recorded from myometrium strips obtained from non-pregnant rabbits in the absence and presence of nicotine. Nicotine led to the increase in the amplitudes of the EFS-evoked contractile responses in a dose-dependent manner. Therefore, the effects of hexamethonium, cadmium, indomethacin, atropine, and N(omega)-Nitro-L-arginine methyl ester hydrochloride were tested on the EFS-evoked contractions in the absence or presence of nicotine to clarify the mechanisms of nicotine-induced potentiation in EFS-evoked contractile responses. Indomethacin, a non-selective cyclooxygenase inhibitor, and hexamethonium, a ganglionic blocker, inhibited nicotine-induced increase in EFS-evoked responses, whereas other chemicals produced no effect. These results suggest that nicotine-induced potentiation may be mediated by nAchRs and prostaglandins. In conclusion, failure of quiescence in the uterus due to increased contractility by nicotine might be one of the factors contributing to infertility in female smokers.

Effects of mexiletine on electrical field stimulation-induced contractile responses in the ipsilateral and contralateral vasa deferentia after unilateral testicular torsion/detorsion.

AIM: To investigate testicular torsion-induced changes on the electrical field stimulation (EFS)-induced contractions in rabbit vasa deferentia and to evaluate the effect of mexiletine. METHODS: 18 male New Zealand albino rabbits were used in this experiment. Rabbits were divided into three groups: (1) control group (n = 6); (2) torsion group (n = 6), and (3) mexiletine group (n = 6). In the control group, vasa deferentia on both sides were harvested. In the torsion and mexiletine groups, the left testes of the rabbits were subjected to 720 degrees of clockwise torsion for 2 h and then detorsion was performed. In the mexiletine group, 50 mg/kg i.p. mexiletine was administered 1 h before detorsion. Following 24 h of the torsion, vasa deferentia on both sides were harvested and 2-cm strips including both the prostatic and epididymal portions were prepared to record EFS-induced contractions. RESULTS: Testicular torsion caused a significant inhibition in both phases of EFS-induced biphasic contractions of the ipsi- and contralateral vasa deferentia. Mexiletine treatment did not affect these inhibitory responses. Torsion/detorsion of the spermatic cord did not alter exogenously applied noradrenaline-induced contractions in both vasa deferentia. However, KCl-induced contractions diminished significantly in ipsilateral vas deferens of the torsion group and mexiletine restored this inhibition. CONCLUSIONS: Unilateral testicular torsion/detorsion leads to inhibition in both phases of EFS-induced biphasic contractions of the ipsi- and contralateral vasa deferentia by causing a defect in presynaptic nerve transmission. However, mexiletine has no effect on this inhibition. Inhibition of the KCl-induced contractions in the ipsilateral vas deferens, which indicates postsynaptic tissue damage, is restored by administering mexiletine 1 h prior to detorsion.

Effects of cannabinoid receptor activation on rabbit bisected vas deferens strips.

1. In the present study, the effects of anandamide and WIN 55,212-2, cannabinoid receptor agonists, were investigated on electrical field stimulation (EFS)-induced biphasic twitch responses obtained from the epididymal and prostatic portions of rabbit vas deferens strips. 2. Anandamide and WIN 55,212-2 dose-dependently inhibited both the first and second phases of the EFS-induced twitch responses recorded from epididymal and prostatic portions of the vas deferens over the concentration range 10(-9) to 3 x 10(-6) mol/L. 3. The cannabinoid CB1 receptor antagonist AM 251 (10(-6) mol/L) and the cannabinoid CB2 receptor antagonist AM 630 (10(-6) mol/L) had no effect on the inhibitory action of anandamide on the biphasic twitch responses in the prostatic and epididymal portions of the rabbit vas deferens. 4. In both the prostatic and epididymal portions of the rabbit vas deferens, AM 251 significantly, but not completely, reversed the inhibitory effect of WIN 55,212-2 on the first phase of the twitch response. In contrast, AM 630 did not have any effect on the inhibitory action of WIN 55,212-2 in the rabbit vas deferens strips. 5. The inhibitory effects of anandamide or WIN 55,212-2 on EFS-induced twitch responses of both the prostatic and epididymal portions of the rabbit vas deferens were not altered in the presence of 10(-5) mol/L naloxone. 6. These results suggest that cannabinoid receptors may have a modulatory role in the regulation of sympathetic transmission in the rabbit vas deferens. However, further investigation is required to characterize the receptors involved.

Effects of amifostine on glycerol-pretreated rabbit kidneys.

Glycerol-induced acute renal failure is an experimental model for myoglobinuric nephropathy. Amifostine is a cytoprotective agent which scavenges the free radicals. Since there is enhanced production of reactive oxygen metabolites in glycerol-induced acute renal failure, we wanted to examine whether amifostine has a protective role against vascular reactivity and histological changes in kidneys isolated from glycerol-pretreated rabbits. Perfusion pressure was recorded from kidneys obtained from rabbits injected with glycerol 3 hr before the experiments and from glycerol-pretreated and non-pretreated rabbits injected with amifostine 30 min. before the experiments. Acetylcholine-induced (10(-8)-10(-5) M) vasodilatation was tested following the construction of submaximal vasoconstriction by phenylephrine. Histological investigation was performed using light microscope. Acetylcholine-induced vasodilatation was found to be significantly decreased in glycerol, glycerol+amifostine and amifostine groups compared to controls at all concentrations. Reduction in acetylcholine-induced vasodilation was more prominent in amifostine group compared to amifostine+glycerol group. There was histological renal damage in all experimental groups and this damage was more pronounced in glycerol+amifostine group. In conclusion, contrary to expectation, amifostine per se led to histological damage and potentiated the histological damage caused by glycerol and produced a decrease in acetylcholine-induced vasodilatation. The mechanisms by which amifostine exerts its effects are not known.

The effects of melatonin on electrical field stimulation-evoked biphasic twitch responses in the ipsilateral and contralateral rat vasa deferentia after unilateral testicular torsion/detorsion.

It is not known whether there is an impairment in vas deferens motility after unilateral testicular torsion/detorsion. Therefore, we aimed to determine whether the electrical field stimulation (EFS)-evoked biphasic contractions are altered in ipsilateral and contralateral rat vasa deferentia obtained from animals exposed to the unilateral testicular torsion/detorsion procedure. We also evaluated the effects of melatonin (MLT), which is a strong antioxidant, on these contractile responses. Rats were subjected to torsion of the left testis for 2 h and then detorsion was performed. Contractility studies were carried out 2 h or 24 h after detorsion. Vas deferens strips were prepared from both the ipsilateral and the contralateral site 2 h or 24 h after the detorsion procedure to record EFS-evoked biphasic twitch responses. The same experimental protocol was repeated for the MLT-treated rats. Both phases of EFS-evoked contractions were decreased after torsion/detorsion in the ipsilateral vas deferens. MLT treatment increased torsion/detorsion-induced reduction of both phases of contractions after 2 h and 24 h. In the contralateral vas deferens, the first phase of EFS-evoked contractions was not changed, while the second phase of contractions was diminished 2 h and 24 h after detorsion. Although MLT decreased the second phase of contractions 2 h and 24 h after detorsion, it reduced the first phase of contractions only 2 h after detorsion. These results suggest that MLT produces an inhibition on EFS-evoked biphasic twitch responses in the ipsilateral and contralateral rat vasa deferentia following unilateral testicular torsion/detorsion in the rat.

Effects of platelet-activating factor on nitrergic transmission in rabbit corpus cavernosum.

AIM: The information currently available suggests that nonadrenergic noncholinergic (NANC) transmitters, particularly nitric oxide, are involved in the relaxation of penile erectile tissues. Platelet-activating factor (PAF) is a chemical mediator and is involved in many physiological and pathophysiological events. It is well known that several of the vascular actions of PAF are mediated by the generation of nitric oxide. We designed this study to test the hypothesis that PAF has an effect on NANC responses in rabbit corpus cavernosum strips. METHODS: Rabbit corpus cavernosum strips were precontracted with phenylephrine (10(-5) mol/L). Isometric tension changes produced by carbachol (10(-9)-10(-5) mol/L), sodium nitroprusside (10(-8)-10(-5) mol/L) and electrical field stimulation (for 10 s at sequential frequencies of 2, 4, 8, 16, and 32 Hz as square-wave pulses of 50 mV) were recorded with a pressure transducer. These relaxations were compared to those obtained in the presence of PAF. RESULTS: PAF had no effect on endothelium-dependent, endothelium-independent or electrical field stimulation-induced NANC relaxation responses in isolated rabbit corpus cavernosum strips. There was no statistically significant difference between the pD(2) and E(max) values for carbachol or sodium nitroprusside in the presence of PAF. CONCLUSIONS: Our results suggest that PAF does not modify the endothelium-dependent, endothelium-independent or electrical field stimulation-induced NANC relaxation responses in isolated rabbit corpus cavernosum strips.