The endogenous cannabinoid and the adrenergic systems in modulation of stress-response

In our modern, fast-paced society, excessive stress (or distress) is a major risk factor for developing a plethora of diseases. There are several neuromediatory systems in the brain that regulate the response to stress, including the adrenergic and endocannabinoid systems. In our experiments, we study the effects of the endocannabinoid system on the restrain stress-induced analgesia (r-SIA). The experiments were done on male Wistar rats. The animals were confined in special restrainers for a period of one hour. The animals were treated with Clonidine (at 4 mg/kg) – a prototypical α2-agonist; Yohimbine – an α2-adrenergic receptor antagonist; Desipramine – a NE reuptake blocker; CB1r agonist anandamide (AEA); CB1r antagonist АМ251 in different combinations. r-SIA was investigated by means of the paw pressure test in order to get a better understanding of the role that the neurotransmitter anandamide plays in the process. The degree to which the levels of r-SIA fluctuated served as an indicator of the degree to which the cannabinoid system and the adrenergic system interacted with one another. Cannabinoids that are administered exogenously were found to reduce levels of r-SIA and modulate the effects of the adrenergic system. These conclusions were reached based on the findings of our research

Differences between paediatric and adult suspected neuropsychiatric adverse drug reactions of Melatonin reported to the European Medicines Agency

Melatonin has been approved as a sleep medication in Europe since 2007. The pharmacological dosages of this substance are much higher than the physiological ones, so it is no surprise that it has potential for many adverse effects. In children melatonin has been used for many years off-label, but in 2018 the Committee for Medicinal Products for Human Use (CHMP) granted paediatric-use marketing authorization for melatonin. We used the European Medicines Agency (EMA) database to compare the distribution of melatonin adverse drug reaction (ADRs) between the pediatric and the adult population. The results will serve as a basis for future research involving melatonin use in specific populations. All ADR reports received in EMA up to 23.03.2019 were analyzed for overall numbers, age and gender. The nature of the ADRs and the most frequently reported drug substances and drug event combinations were evaluated using MedDRA 21.0. As of 27th March 2019, EudraVigilance contained 1061 spontaneous reports. After excluding all the cases with other suspected or concomitant drugs, we are left with 177 cases. In children ADRs were generally associated with central nervous system (CNS) excitability, whereas in adults there was mainly inhibition. The present study focused on the ADR reports of melatonin in one of the largest databases. Future research of melatonin in the pediatric population is needed, because the current SmPCs lack such information, and in the cases of melatonin use in children are increasing in recent years

Aryl hydrocarbon receptors as potential therapeutic targets

Aryl hydrocarbon receptors (AhR) are regulators of the expression of cytochrome P-450 isoforms, mediating a wide variety of the effects of substances from the endogenous or exogenous origin, including those produced from the microbiome. An exciting new aspect of their activity is their localization in the brain and their potential to modulate the action of the immune system. AhR is emerging as an essential toxicological and therapeutic target for neuromodulation. Further studies are needed for elucidating their utility as drug-targets

Attenuation of Hypothyroidism-Induced Cognitive Impairment by Modulating Serotonin Mediation

Thyroid hormones play an important role in the modeling of neural networks in the brain. Besides its metabolic effects, thyroid dysfunction, and hypothyroidism in particular, is frequently associated with cognitive decline and depressive-like behavior. The current study aimed to examine the changes in behavior, cognition, and memory in rats with propylthiouracil-induced overt hypothyroidism. The behavior and cognition were assessed using the open field test, T-maze, and novel object recognition test. We found significant differences in the behavioral patterns of the hypothyroid animals showing a reduction in locomotor activity, frequency of rearing, and impaired memory function compared to the euthyroid controls. As serotonin is an essential biomarker regulating cognition and mood, we tried to modulate the serotonin mediation in hypothyroid animals through tryptophan administration. Treatment with 5-hydroxy-tryptophan (5-OH-TRP) intraperitoneally for 10 days or directly into the hippocampus as a single injection led to attenuation of the hypothyroidism-induced cognitive and memory decline. A staggering amount of research is suggesting that the common denominators in the pathophysiology of depression and the behavior changes in hypothyroidism are the hippocampal complex and the distorted serotonin metabolism. In our study, it was observed a significant alleviation of cognitive impairment and an improvement of memory performance in hypothyroid rats after 5-OH-TRP administration. Current results are promising and may serve as groundwork for further investigation of functional and structural changes in the hippocampus during a hypothyroid state, and in particular, the effects of serotonin mediation in hypothyroid-associated depressive-like behavior

Association between Helicobacter pylori infection and the presence of anti-sperm antibodies

The aim of this study was to investigate the possible association between serum anti-Helicobacter pylori antibodies and anti-sperm antibodies (ASA) in patients with gastroduodenal diseases caused by H. pylori, infertile patients positive for ASA and healthy fertile blood donors as controls. Serum ASA were studied by sperm agglutination tests, sperm immobilization test and ELISA against sperm antigens (ELISAsp). Serum IgG anti-H. pylori antibodies were detected by ELISA (ELISAHp). The tests revealed significantly higher incidence of ASA in patients with gastroduodenal diseases compared to the controls (P < 0.0001). The median levels of both types of antibodies were significantly higher in infertile patients than in patients with upper gastroduodenal diseases in all tests applied (sperm agglutination and immobilization tests P < 0.0001; ELISAsp P = 0.006; ELISAHp, P = 0.0008). Significant linear correlation was found between anti-H. pylori antibodies and ASA detected by sperm immobilization test (r = 0.613, P = 0.05) in the group of patients with gastroduodenal disease, as well as a weak linear correlation was established between anti-H. pylori antibodies and ASA in ELISAsp (r = 0.275, P = 0.0051) in the same group. These results suggest that H. pylori infection may play a role in the induction of ASA

Characteristics of 2.45 GHz Surface-Wave-Sustained Argon Discharge for Bio-Medical Applications

Cold atmospheric plasma (CAP) applications in various fields, such as biology, medicine and agriculture, have significantly grown during recent years. Many new types of plasma sources operating at atmospheric pressure in open air were developed. In order to use such plasmas for the treatment of biological systems, plasma properties should fulfil strong requirements. One of the most important is the prevention from heating damage. That is why in many cases, the post-discharge region is used for treatment, but the short living particles in the active discharge zone and reactions with them are missed in that case. We use the active region of surface-wave-sustained argon plasma for biological systems treatment. The previous investigations showed good bactericidal, virucidal, seeds germination and decontamination effects at a short treatment time, but the discharge conditions for bio-medical applications need specific adjustment. A detailed theoretical and experimental investigation of the plasma characteristics and their possible optimization in order to meet the requirements for bio-medical applications are presented in this paper. The length of the plasma torch, the temperature at the treatment sample position and the microwave radiation there are estimated and optimized by the appropriate choice of discharge tube size, argon flow rate and microwave power

Platelet Distribution Width and Increased D-Dimer at Admission Predicts Subsequent Development of ARDS in COVID-19 Patients

In the current pandemic of coronavirus disease (COVID-19), the identification of the patients admitted with severe infection&ndash;who are disposed to a high risk of acute respiratory distress syndrome (ARDS) development, is of a major significance for the determination of the appropriate therapeutic strategy. Laboratory records in admission were retrospectively reviewed from 493 cases of severe COVID-19 divided into two groups: Group 1 with ARDS and Group 2 without ARDS. The platelet distribution width (PDW) difference between Group 1 and Group 2 is significant&ndash;15.10 &plusmn; 2.08 fl for those who developed ARDS versus 12.94 &plusmn; 2.12 fl for those without ARDS. The sensitivity and the specificity of this parameter is lower than that of D-dimer. After grouping of the PDW values into intervals and combining them with the rate of increase in D-dimer (D-PDWf index) to form a forecasting index, a significant increase in the specificity and sensitivity of the two parameters is identified&ndash;area under the ROC curve (AUC) is 0.874 for D-PDWf index, with respective AUC for PDW 0.768 and AUC for D-dimer 0.777. Conclusion: PDW is a significant predictive parameter at admission for subsequent development of ARDS in patients, with increased significance in combination with the degree of increase in D-dimer