Background: The antidepressant and anxiolytic effects of selenium (Se) have been proven in many studies. This work was aimed at confirming these activities of its inorganic form—sodium selenite—and examining the possible synergy of action with antidepressants and diazepam. Methods: The antidepressant- and anxiolytic-like activity of Se was assessed using forced swim tests (FSTs) and elevated plus-maze test (EPMs). Spontaneous locomotor activity was measured using photoresistor actimeters. The experiments were conducted on male Albino Swiss mice. Results: Sodium selenite (0.5 mg/kg) reduced the immobility time in the FSTs and extended time spent in the open arms of EPMs without affecting locomotor activity The combined administration of Se at an ineffective dose (0.25 mg/kg) together with imipramine (15 mg/kg), fluoxetine (5 mg/kg), tianeptine (10 mg/kg), but not with reboxetine (2.5 mg/kg), resulted in a reduction of immobility time in FSTs, and with a threshold dose of diazepam (0.25 mg/kg) led to the prolongation of time spent in the open arms of the EPM. Moreover, the antidepressant-like effect of Se (0.5 mg/kg) was significantly reduced by pretreatment with p-chlorophenylalanine (100 mg/kg). Conclusions: The results may indicate the participation of serotonergic transmission to antidepressant action of Se and GABA-ergic transmission to its anxiolytic effects.
How to get a new drug to market? How much time does it take to go from the idea to implementation? In this study we followed the path drugs take from synthesis to introduction to the market. In doing so, articles in the PubMed and the Google Scholar database have been analyzed using the keywords: drug development, drug design, lead compound, preclinical trials, clinical trials. The available literature was subjectively selected due to its usefulness in the topic. Based on the obtained articles, we presented the stages that a would-be drug takes on the way from the idea to marketing. Herein, it is underlined that the process of creating new drugs is long, extremely labor-intensive, and involves many restrictions in the context of the use of animals, as well as humans
Erectile dysfunction (ED) is the inability to develop and/ or maintain an erection necessary to have a successful sexual performance [1]. It has been diagnosed in an increasing number of men around the world [2]. According to the sexuality study conducted by Professor Izdebski, 1 out of 10 men in Poland suffers from ED. The problem is found among men of any age, however, 60% of all patients are between 40 and 60 years old, thus in their prime, and, hence, still have the desire to fully enjoy life. Moreover, among men older than 60, ED occurs in more than 50% of the population [3]. Unfortunately, out of 1.5 million men suffering from ED, only 15% seek medical help. Not only are the effects of ED detrimental to a man's self-esteem, but they also have a negative influence on his partner and his sexual relationships. Still, in spite of a growing awareness within society, the problem remains perceived as embarrassing, which leads patients to treat themselves on their own, delaying a visit to their doctors even up to several years. Indeed, 16% of all patients only decide to seek professional help more than 4 years after the first symptoms are observed [4]. THE MECHANISM OF ERECTIONWhile flaccid, a penis is controlled by the sympathetic nervous system responsible for involuntarily reactions. Through the effect of adrenaline, vascular smooth muscles and the trabeculae of the corpus cavernosum are shrunk, and the flow of blood is low. As a result of sexual arousal (mechanical or psychogenic), the activity of the sympathetic nervous system decreases, while sympathetic neurons from the NANC group (nonadrenergic, noncholinergic) prevail and release nitric oxide -NO, which stimulates relaxation of the corpus cavernosum smooth muscle and produces erection. The compounds which are additionally released by these neurons, for instance, adenosine or vasoactive intestinal peptide (VIP), also result in an increased production of NO in the endothelium cells. NO connects with "guanylyl cyclase receptors", which conditions the production of highly energetic cyclic guanosine monophosphate (cGMP), which lowers the calcium ion concentration (Ca 2+ ) in muscle cells. As a consequence, vascular smooth muscles relax and the flow of blood is increased, which results in the stiffening of a penis and erection. After ejaculation, a penis returns to its flaccid state. The erection recedes due to the effect of phosphodiesterase type 5 enzyme (phosphodiesterase type 5, PDE-5), which causes the decomposition of cGMP [5,6].
of diagnostic value of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as inflammatory indicators and indirect endothelial dysfunction markers in patients with acute pulmonary embolism.
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