Central nervous system agents in medicinal chemistry最新文献

The nervous system regulates the visual system through neurotransmitters that play an important role in visual and ocular functions. One of those neurotransmitters is acetylcholine, a key molecule that plays a variety of biological functions. Moreover, acetylcholinesterase, the enzyme responsible for the hydrolysis of acetylcholine, is implicated in cholinergic function. However, several studies have demonstrated that in addition to their enzymatic functions, acetylcholinesterase exerts non-catalytic functions. In recent years, the importance of evaluating all possible functions of acetylcholine-acetylcholinesterase has been shown. Nevertheless, there is evidence suggesting that cholinesterase activity in the eye can regulate some biological events both in structures of the anterior and posterior segment of the eye and, therefore, in the visual information that is processed in the visual cortex. Hence, the evaluation of cholinesterase activity could be a possible marker of alterations in cholinergic activity in both ocular and systemic diseases.

Background: Most studies of the prevalence of cannabis use among patients with schizophrenia used a self-report as declared by the patient himself. We hypothesize that patients with schizophrenia did not tell the truth and might underreport their use for many reasons to be discussed later. Indeed, the under-report of cannabis use among these patients can affect the effectiveness of their treatment.

Aims: To assess the degree of agreement between the prevalence values obtained from patients' reports and the results of the toxicological tests.

Methods: A cross-sectional study was carried out on 403 patients with schizophrenia. A sociodemographic, psychiatric history and illicit drug use profile was performed for each patient. We assessed the patients with the Positive and Negative Syndrome Scale (PANSS), Calgary Depression score (CDSS), Barratt Impulsiveness Score (BIS-10) and Medication Adherence Rating Scale (MARS). The consumption of cannabis used was confirmed with MINI International Neuropsychiatric Interview (MINI-DSM IV) and using toxicological analysis.

Results: Among the 403 patients who consented to give their urine samples, 49.1% (198/403) tested positive for cannabis, and 41.41% (82/198) underreported their use. The sensitivity and specificity of the questionnaire were 0.58 and 0.74. Based on the comparison between sociodemographic and psychiatric history data of patients who self-report and underreport their cannabis use, no significant difference was observed except for the duration of cannabis use and the score on the medication adherence scale. Moreover, it was found that impulsivity, PANSS score, CDSS score, and the type of schizophrenia are not involved in predicting the underreporting of cannabis use.

Conclusion: The rate of patients who under-report cannabis use is important. Therefore, toxicological analysis is becoming relevant for identifying drug use among schizophrenic patients and in the addictive comorbidity research field.

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Suicides on railway tracks are one of the most drastic ones. No research concerning this phenomenon has been done to this date in Poland. This article focuses on the connection between suicidal behaviors on Polish railway tracks and sociodemographic traits and presents risk factors.

Background: The suicide behavior is largely spread among many European countries. Of these, Poland ranks 22nd in terms of suicide attempts. This study aims to highlight the suicide attempts rates on Polish railways lines and their main risk factors.

Limitations: Limited number of available statistical data before 2013.

Method: Statistical review of the available Central Police headquarters database and analyses of the influence of the risk factors on people's awareness during the suicide attempts and their geographical distribution in Poland during the years 2013 - 2016. The prevalence of railway suicides in individual voivodeships (provinces) in Poland have been indicated in a 3D map.

Results: There were 834 cases of railway suicide fatalities across the entire country. Of the total suicide statistics by any means, 3.75% are railway related. The average known age of those committing railway suicides were: 37.9 years for men (n = 627) and 34.6 for women (n = 155). In most cases, suicides were committed by bachelors (54.3%). The largest group of people who committed suicide had a primary level of education (42.0%). Among the suicides, a significant group are unemployed (45.2%). Alcohol intoxication have been established as responsible for a person's lower awareness of his actions in 70.9% of cases. Almost 63.3% of people had a higher propensity for suicidal ideation and behavior, resulting in their being treated for mental health issues.

Conclusion: Alcohol intoxication, illegal narcotics and psychotropic medication are responsible for a person's lower awareness during his ore her actions, in most of the cases of suicide on Polish railway lines.

Background: Ischemic stroke is a serious public health problem. Despite extensive researches focusing on the area, little is known about novel treatments.

Objective: In this study, we aimed to investigate the effects of Capparis spinosa (C. spinosa) extract in the middle cerebral artery occlusion (MCAO) model of ischemic stroke.

Methods: Wistar rats underwent 30-min MCAO-induced brain ischemia followed by 24 h of reperfusion. C. spinose was administrated orally once a day for 7 days before the induction of MCAO. The neurologic outcome, infarct volume (TTC staining), histological examination, and markers of oxidative stress, including total thiol content, and malondialdehyde (MDA) levels, were measured 24hr. after the termination of MCAO.

Results: Pretreatment with C. spinosa reduced neurological deficit score, histopathological alterations, and infarct volume in treated groups compared to the stroke group. Furthermore, pretreatment with C. spinosa extract significantly reduced the level of MDA with concomitant increases in the levels of thiol in the brain tissues compared to the stroke group.

Conclusion: Our study demonstrates that C. spinosa extract effectively protects MCAO injury through the attenuation or the suppression of the oxidative stress.

Background: Epilepsy, the second most frequent neurological disease, is a chronic disorder with a high lifetime prevalence. Therefore, various studies are needed to find new effective therapeutic agents to treat seizures or prevent their complications. In this study, we investigated the effects of thiamine, melatonin and their combination on pentylenetetrazol (PTZ)-induced tonic-clonic seizures in mice.

Methods: Male mice were randomly divided into six groups, including control, seizure control, diazepam, melatonin, thiamine and melatonin, and thiamine combination groups. Drugs were given orally in drinking water for 14 days. On the 15th day, the seizure was induced (except the control group) by intraperitoneal injection of PTZ. In all groups, the time between the injection and the start of the seizure (latency), and also the length of the seizure attack (duration), were measured in a 30-minute period. After measuring the latency and duration in all groups, mice were killed by CO₂ Box and their brains were dissected to be analyzed for malondialdehyde (MDA) level as a marker of oxidative stress.

Results: The seizure duration was significantly lower in the groups of melatonin, thiamine and thiamine and melatonin combination compared to the seizure control group. The latency times in these groups were significantly greater than in the seizure control group. Moreover, MDA concentrations were lower in these groups compared to the seizure control group.

Conclusion: Thiamine, melatonin and their combination can decrease the duration time of seizure and increase the latency period, which may result from inhibition of oxidative stress in the brain.

Background: Morphine independently reduces the expression level of Brain-derived Neurotrophic Factor (BDNF) and Cyclic-AMP Response Element Binding protein (CREB). BDNF and CREB play a vital role in protecting and regulating the proper functioning of neurons. There has not been any study on the effect of methadone maintenance treatment and its comparison with morphine. Therefore, this study was conducted to examine the effect of methadone maintenance on the expression of BDNF and CREB genes in brain VTA of male morphine treated rats.

Methods: In this study, 24 Wistar rats (200-250g) were assigned to three experimental groups: 1) Animals without morphine treatment (control); 2) Morphine treated animals (10 mg/kg, twice/day through subcutaneous injection for 21 days); 3) Animals under methadone maintenance after treatment with morphine (maintenance dose of methadone was achieved during 14 days equal to 1 mg per 100 ml at the first week and 2.5 mg per 100 ml at second week). To evaluate the expression of BDNF and CREB genes, real time PCR method was used, and ELISA was applied to measure the serum level of BDNF protein at the end of the experiment.

Results: According to the findings of this study, similar to morphine treated group, methadone maintenance in morphine treated animals led to a significant reduction in the expression of BDNF and CREB genes at VTA as well BDNF serum level compared with the control group.

Conclusion: It was concluded that methadone, like morphine, causes a significant reduction in the expression of BDNF and CREB genes in the brain VTA area of rats as well as BDNF serum level compared with the control group.

Background: Ascorbic acid (AA) is a water-soluble vitamin that is concentrated in the brain in large quantities. There have been reports that it is essential for proper brain functioning. However, there is insufficient information on the possible effects of dietary fortification with AA on the health of the brain.

Objective: This study examined the effects of dietary fortification of rodent chow with AA on neurobehaviour, antioxidant status, lipid peroxidation, and inflammatory/apoptotic markers in the brain of healthy mice.

Methods: Mice were randomly assigned into four groups of ten animals each. Groups were normal control [fed rodent chow], and three groups were fed AA-fortified chow at 100, 200, and 300 mg/kg of feed, respectively, for eight weeks. Behavioural tests {Open field, Y-maze, radial-arm maze, and elevated plus maze (EPM)} were carried out on day 57. Twenty-four hours after the last behavioural test, animals were euthanised, and the brains were excised and homogenised for assessment of brain acetylcholinesterase activity, lipid peroxidation, antioxidant status, inflammatory and apoptotic markers.

Results: Ascorbic acid fortified diet was associated with concentration-dependent changes in body weight, open-field behaviours, working-memory, and anxiety indices. Also, brain levels of malondialdehyde, caspase-3, and TNF-α decreased, while superoxide dismutase activity, total antioxidant capacity, and IL-10 level increased.

Conclusion: Dietary AA fortification with concentrations up to 300 mg/kg of feed was associated with sustained improvement in neurobehavioural and biochemical parameters in the brain of healthy mice, reiterating additional health benefits of AA fortification beyond the prevention of nutritional deficiencies.