Angular-Substituted [1,4]Thiazino[3,4-a]Isoquinolines: Biological Evaluation and In Silico Studies on DPP-IV Inhibition.

Recent studies have discovered that aryl-substituted pyrido[2,1-a]isoquinolines have the potential to be highly active DPP IV inhibitors. In previous studies, we reported a novel synthetic approach for the construction of their sulfur-containing bioisosteric [1,4]thiazino[3,4-a]isoquinolines analogues, incorporating an additional aryl substituent. The present study aims to investigate the DPP IV inhibitory activity and cytotoxicity of the synthesized molecules by in vitro assay.

Detrimental effect of prenatal progesterone exposure on anxiety and depressive-like responses in adult male and female rat offspring: Role of plasma, hippocampal corticosterone and hippocampal progesterone receptors.

In clinical practice, the use of exogenous progesterone (Pro) is often required in assisted reproduction programs due to reduced levels of the hormone and the risk of miscarriage. Exposure to the hormone reduces anxiety in rodents, but the long-term effects of prenatal exposure in adult offspring are unknown. Therefore, the present study was designed to investigate the effect of prenatal Pro treatment on anxiety- and depression-like behavior and the effect on plasma, hippocampal corticosterone (CORT) and hippocampal progesterone receptor (PR) in young adult male and female rat offspring.

The Role of Piromelatine on Peripheral and Hippocampal Insulin Resistance in Rat Offspring Exposed to Chronic Maternal Stress.

Prenatal stress (PNS), which alters the hypothalamic-pituitary-adrenal axis function in the offspring, predisposes to insulin resistance (IR) in later life and is associated with numerous disorders, including cognitive and memory impairments. At present, our main goal is to assess the effects of chronic piromelatine (Pir) administration, a melatonin analogue, on PNS-provoked IR in the periphery and the hippocampus in male and female offspring. Pregnant Sprague-Dawley rats were exposed to chronic stress (one short-term stressor on a daily basis and one long-term stressor on a nightly basis) from the first gestation week until birth.

The role of melatonin deficiency induced by pinealectomy on motor activity and anxiety responses in young adult, middle-aged and old rats.

Background: Aging affects anxiety levels in rats while the pineal gland, via its hormone melatonin, could modulate their inherited life "clock." The present study aimed to explore the impact of plasma melatonin deficiency on anxiety responses and the possible involvement of the hypothalamic-pituitary-adrenocortical (HPA) axis and heat shock proteins (Hsp) 70 and 90 in the frontal cortex (FC) and the hippocampus in young adult, middle-aged and elderly rats with pinealectomy.

Results: Melatonin deficiency induced at different life stages did not affect the lifespan of rats.

Comparative Analysis of Anticonvulsant Activity of and 5,5'-Diphenylhydantoin Schiff Bases.

Recently, the four 5,5'-diphenylhydantoin Schiff bases, possessing different aromatic species () were synthesized, characterized, and evaluated for anticonvulsant activity in combination with phenytoin. In the present study, the and compounds were selected, based on their anticonvulsant potency, and compared with their isomers, prepared after a one-hour exposure to the UV source, for their anticonvulsant potency in the maximal electroshock (MES) test and the kainate (KA)-induced status epilepticus (SE) test in mice. In the MES test, the compound exhibited superior to phenytoin and isomer activity in the three tested doses, while the compound entirely suppressed the electroshock-induced seizure spread at the highest dose of 40 mg/kg.

Sex-Dependent Effect of Chronic Piromelatine Treatment on Prenatal Stress-Induced Memory Deficits in Rats.

Prenatal stress impairs cognitive function in rats, while Piromelatine treatment corrects memory decline in male rats with chronic mild stress. In the present study, we aimed to evaluate the effect of chronic treatment with the melatonin analogue Piromelatine on the associative and spatial hippocampus-dependent memory of male and female offspring with a history of prenatal stress (PNS). We report that male and female young adult offspring with PNS treated with a vehicle had reduced memory responses in an object recognition test (ORT).

Pre- and Post-Endurance Training Mitigates the Rat Pilocarpine-Induced Status Epilepticus and Epileptogenesis-Associated Deleterious Consequences.

Epilepsy is a brain disorder characterized by recurrent epileptic seizures and neurobiological, physiological, mood, and cognitive consequences. In the last decade, the beneficial effects of regular physical exercise have been investigated in patients with neurodegenerative diseases such as epilepsy. However, data on its beneficial effects and underlying mechanisms are still insufficient.

The anticonvulsant effect of chronic treatment with topiramate after pilocarpine-induced status epilepticus is accompanied by a suppression of comorbid behavioral impairments and robust neuroprotection in limbic regions in rats.

Epilepsy is a widespread neurological disorder frequently associated with a lot of comorbidities. The present study aimed to evaluate the effects of the antiseizure medication topiramate (TPM) on spontaneous motor seizures, the pathogenesis of comorbid mood and cognitive impairments, hippocampal neuronal loss, and oxidative stress and inflammation in a rat model of temporal lobe epilepsy (TLE). Vehicle/TPM treatment (80 mg/kg, p.

Prevalence of Sensu Lato in Ticks Collected from Kaylaka Park in Pleven, Bulgaria.

We aimed to determine the presence and distribution of sensu lato (s.l.) in ticks collected from urbanized and wild areas in Kaylaka Park (Bulgaria).

Estimation of (Acari: Ixodidae) Populations of Kaylaka Park in the Town of Pleven, Bulgaria.

(1) Background: Ticks are vectors of a large number of pathogenic microorganisms, which cause serious diseases in both humans and animals. Kaylaka Park is located in northern Bulgaria close to the city of Pleven. Part of the park is urbanized and visited daily by many citizens.

Chronic agomelatine treatment alleviates icvAβ-induced anxiety and depressive-like behavior through affecting Aβ metabolism in the hippocampus in a rat model of Alzheimer's disease.

Recently, we reported that the atypical antidepressant agomelatine (Ago) exerted a beneficial impact on behavioral changes and concomitant neuropathological events in icvSTZ rat model of sporadic Alzheimer diseases (AD). In the present study, we aimed to explore the effect of Ago (40 mg/kg, i.p.

Chronic Piromelatine Treatment Alleviates Anxiety, Depressive Responses and Abnormal Hypothalamic-Pituitary-Adrenal Axis Activity in Prenatally Stressed Male and Female Rats.

The prenatal stress (PNS) model in rodents can induce different abnormal responses that replicate the pathophysiology of depression. We applied this model to evaluate the efficacy of piromelatine (Pir), a novel melatonin analog developed for the treatment of insomnia, in male and female offspring. Adult PNS rats from both sexes showed comparable disturbance associated with high levels of anxiety and depressive responses.

Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation.

Background: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE.

Methods: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.

Plasma lipoprotein(a) concentration as an independent predictor of hemodynamic progression of aortic valve stenosis.

Calcific aortic valve disease (CAVD) is a common cardiovascular disorder of high social significance. This study aimed to identify independent predictors of hemodynamic progression of CAVD. The relationship between some risk factors, including the rs10455872 polymorphism in the intron 25 of the lipoprotein(a) [Lp(a)] coding region and the plasma Lp(a) concentration, and CAVD severity were prospectively examined in 114 patients.

Endurance training exerts time-dependent modulation on depressive responses and circadian rhythms of corticosterone and BDNF in the rats with pinealectomy.

Pinealectomy can cause a disturbance in emotional status and circadian rhythms of the endocrine and metabolic functions in the body. Endurance training is considered a part of the complex therapy of dysfunctions driven by changes in circadian dynamics of many physiological indicators. In the present study, we aimed to study the effect of endurance training on depressive behavior induced by pinealectomy in rat.

Effect of endurance training on diurnal rhythms of superoxide dismutase activity, glutathione and lipid peroxidation in plasma of pinealectomized rats.

Melatonin deficit is characterized by disturbed circadian rhythms of many physiological and biochemical parameters including markers of oxidative stress. Moderate endurance training exerts protection against oxidative stress. In the present study, we aimed to explore the impact of endurance treadmill training on disturbed rhythmic fluctuations of some markers of oxidative stress in pinealectomized rats.

Agomelatine treatment corrects impaired sleep-wake cycle and sleep architecture and increases MT receptor as well as BDNF expression in the hippocampus during the subjective light phase of rats exposed to chronic constant light.

Rationale: Exposure to chronic constant light (CCL) has a detrimental impact on circadian rhythms of motor activity and sleep/wake cycles. Agomelatine is an atypical antidepressant showing a chronotropic activity.

Objectives: In this study, we explored the role of melatonin (MT) receptors and brain-derived neurotrophic factor (BDNF) in the brain in the mechanism underlying the effects of agomelatine on diurnal variations of motor activity, sleep/wake cycle, and sleep architecture in a rat model of CCL.

Antidepressant agomelatine attenuates behavioral deficits and concomitant pathology observed in streptozotocin-induced model of Alzheimer's disease in male rats.

Experimental findings suggest that the melatonin system has a beneficial role in models of Alzheimer's disease (ADs). The aim of the present study was to explore whether the atypical antidepressant agomelatine (Ago), which is a melatonin MT and MT agonist and 5-HT antagonist, is effective against behavioral, biochemical and histological impairments in streptozotocin (STZ)-induced model of ADs in male rats. Male Sprague Dawley rats were treated intraperitoneally (i.

Anticonvulsant effect of anacardic acid in murine models: Putative role of GABAergic and antioxidant mechanisms.

Epilepsy is a neurological disease affecting people of all ages worldwide. Side effects of antiepileptic drugs and their association with oxidative stress stimulate the search for new drugs, which would be more affordable with fewer adverse effects. Accordingly, the aim of the present work is to evaluate the anticonvulsant effect of anacardic acid (AA), a natural compound extracted from cashew liquid (Anacardium occidentalis), in murine models, as well as its antioxidant actions in Saccharomyces cerevisiae.

Agomelatine treatment corrects symptoms of depression and anxiety by restoring the disrupted melatonin circadian rhythms of rats exposed to chronic constant light.

Desynchronization of circadian rhythms is a hallmark of depression. The antidepressant agomelatine, which is an MT/MT melatonin receptor agonist/5-HT serotonin receptor antagonist has advantages compared to the selective serotonin reuptake inhibitors as a circadian phase-shifting agent. The present study was designed to explore whether agomelatine is able to have an antidepressant effect on rats exposed to chronic constant light (CCL) for 6 weeks.

Chronic agomelatine treatment prevents comorbid depression in the post-status epilepticus model of acquired epilepsy through suppression of inflammatory signaling.

Inflammatory signal molecules are suggested to be involved in the mechanism underlying comorbid depression in epilepsy. In the present study, we tested the hypothesis that the novel antidepressant agomelatine, a potent melatonin MT and MT receptor agonist and serotonin 5HT receptor antagonist, can prevent depressive symptoms developed during the chronic epileptic phase by suppressing an inflammatory response. Chronic treatment with agomelatine (40 mg/kg, i.

Agomelatine protects against neuronal damage without preventing epileptogenesis in the kainate model of temporal lobe epilepsy.

Recent studies about the novel antidepressant agomelatine, which is a mixed MT and MT melatonin receptor agonist and 5HT serotonin receptor antagonist possessing an anticonvulsant and neuroprotective action, suggest that it may have potential to contribute against epileptogenesis and epilepsy-induced memory impairment. In order to ascertain whether protection of some brain structures could suppress epileptogenesis, in the present study, we evaluated the effect of chronic post-status treatment with agomelatine on epileptogenesis, behavioral and neuronal damage induced by kainate acid (KA) status epilepticus (SE). Agomelatine/vehicle treatment (40mg/kg, i.

Serum Concentrations of Endothelin-1 and Matrix Metalloproteinases-2, -9 in Pre-Hypertensive and Hypertensive Patients with Type 2 Diabetes.

Endothelin-1 (ET-1) is one of the most potent vasoconstrictors known to date. While its plasma or serum concentrations are elevated in some forms of experimental and human hypertension, this is not a consistent finding in all forms of hypertension. Matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9), which degrade collagen type IV of the vascular basement membrane, are responsible for vascular remodeling, inflammation, and atherosclerotic complications, including in type 2 diabetes (T2D).

Consequences of long-term treatment with agomelatine on depressive-like behavior and neurobiological abnormalities in pinealectomized rats.

Previous data have shown that the rat model of melatonin deficit can cause a number of neurobiological aberrations. The aim of the present study was to determine whether the antidepressant drug agomelatine, a MT1/MT2 melatoninergic receptor agonist/5-HT2C receptor antagonist is able to prevent some of the behavioral, biochemical and cellular abnormalities induced by pinealectomy. The injection of agomelatine (40 mg/kg, i.