Biological activity of Melatonin and Some Unexpected Effects of Dynamization

Author(s):  
Olga Borisovna Zhdanova ◽  
RASSOKHIN Dmitri Vladimirovich ◽  
OKULOVA Iraida Ivanovna ◽  
Chasovskih Olga Vladimirovna

Melatonin was found in animals, plants and bacteria. In animals, it is a hormone that anticipates the daily onset of darkness. In animals, melatonin is the hormone of regulation of the circadian rhythms and physiological functions such as sleep timing, blood pressure regulation, seasonal reproduction and many others. Melatonin is known to aid in reducing the effects of jet lag Melatonin appears also to have some use against the sleep problems of people who work rotating or night shifts. Melatonin has many protective properties, such as converting cholesterol to bile, preventing oxidative stress, may help reduce some types of headaches and protect against radiation-induces cellular damage. Melatonin in comparison to placebo is effective for reducing preoperative anxiety in adults when given as premedication. Melatonin may also reduce postoperative anxiety. It appears to cause few side-effects as tested in the short term, up to three months, at low doses. Two systematic reviews in 2005 and 2006 showed that there were no adverse effects of exogenous melatonin in several clinical trials and those comparative trials found that the adverse effects headaches, dizziness, nausea and drowsiness were reported about equally for both melatonin and placebo. Prolonged-release melatonin is safe with long-term use of up to 12 months. However, «natural» melatonin does not mean the best. Melatonin is made of the animal tissue can be contaminated with viruses or proteins that may be dangerous. Mad cow disease may cause changes in supplements made from animal brain tissue. One of the ways of adverse reaction elimination is applying a dynamicizing form of melatonin. Materials and methods. Melatonin (Mel 3ch) was prepared and presented to us with pleasure by Pralnilov A. I. The main aim of the study is to examine the influence of dynamicizing form of melatonin on hair structure in white laboratory mice and rats, Chinese hamsters, 2 years old. During the experiment the following tasks were solved: 1) To examine normal hair structure in white laboratory mice and rats, Chinese hamsters and to study the influence of dynamicizing form of melatonin on animal hair structure. 2) To examine animal behaviour and appearance 3)To estimate mice strength before and after taking melatonin White laboratory mice which belong to the vivarium of Kirov State Medical Academy and rats which belong to the vivarium of Kirov State Agricultural Academy are taking dynamicizing form of melatonin (mel-3CH) in the dose of 5 drops per 20 ml of water during 14 days. After two groups of the animals are organized: control group (7 animals) and the experimental group (7 animals). The experimental animals were injected subcutaneously in the interscapular region by melatonin-retard in the dose of 1 mg per 1 animal. In the control group, this drug is not injected. Hair is held on the subject glass in the 15 % solution NaOH during 5 min. The first swimming of animals was conducted with the aim to randomize resistance to physical exercises of animals. Every male, one by one, is taken to cylinder with water d = 18 cm, h = 40 cm for free swimming. Temperature of water maintains is in the range 29-30 C. Results. The investigation has shown that the hair structure, fleece and activity of the rodents taking mel 3ch from the 5th to the 14th days are being improved. The animal hair becomes bright, healthy and thick. The microscopic examination showed perfect adhering of the cuticle to the cortical layer and that the bottom and the cortical layer had become dense. In the control groups the hair remained faint and tousled. The microscopic examination showed delamination of the cortical layer from the bottom and the cuticle; the bottom had broken structure. The study showed that white laboratory mice taking dynamicizing form of melatonin in the dose of 5 drops per 20 ml of water during 14 days had improved their hair structure and fleece quality. Compulsory swimming method confirmed that dynamicizing form of melatonin increased adaptability of the animals. The time of swimming was 2,5 times more in comparison with the control group.

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 340
Author(s):  
Fernando Salvador ◽  
Beatriz Lobo ◽  
Lidia Goterris ◽  
Carmen Alonso-Cotoner ◽  
Javier Santos ◽  
...  

Background: The aim of the present study is to describe the occurrence of Blastocystis sp. detection among asymptomatic subjects and patients with irritable bowel syndrome in order to evaluate the potential association between irritable bowel syndrome and the parasitic infection. Methods: Cross-sectional study where adult patients with irritable bowel syndrome diagnosed according to Rome IV criteria were included. A control group was formed by asymptomatic subjects older than 18 years. Exclusion criteria were: immunosuppressive condition or having received any drug with demonstrated activity against Blastocystis sp. within the last 6 months before study inclusion. Epidemiological and clinical information was collected from all included participants. Two stool samples were obtained from all participants: one sample for microscopic examination and one sample for Blastocystis sp. PCR detection. Blastocystis sp. infection was defined by the positivity of any of the diagnostic techniques. Results: Seventy-two participants were included (36 asymptomatic subjects and 36 patients with irritable bowel syndrome). Thirty-five (48.6%) were men, and median age of participants was 34 (IQR 29–49) years. The overall rate of Blastocystis sp. carriage was 27.8% (20/72). The prevalence assessed through microscopic examination was 22.2% (16/72), while the prevalence measured by PCR was 15.3% (11/72). When comparing the presence of Blastocystis sp. between asymptomatic subjects and IBS patients, we did not find any statistically significant difference (36.1% vs. 19.4% respectively, p = 0.114). Conclusions: regarding the occurrence of Blastocystis sp., no differences were found between asymptomatic participants and patients with irritable bowel disease irrespective of the diagnostic technique performed.


Author(s):  
Bente Storm Mowatt Haugland ◽  
Mari Hysing ◽  
Asle Hoffart ◽  
Åshild Tellefsen Haaland ◽  
Jon Fauskanger Bjaastad ◽  
...  

AbstractThe potential effect of early intervention for anxiety on sleep outcomes was examined in a sample of adolescents with anxiety (N = 313, mean 14.0 years, SD = 0.84, 84% girls, 95.7% Norwegians). Participants were randomized to one of three conditions: a brief or a standard-length cognitive-behavioral group-intervention (GCBT), or a waitlist control-group (WL). Interventions were delivered at schools, during school hours. Adolescents with elevated anxiety were recruited by school health services. Questionnaires on self-reported anxiety symptoms, depressive symptoms, and sleep characteristics were administered at pre- and post-intervention, post-waitlist, and at 1-year follow-up. Adolescents reported reduced insomnia (odds ratio (OR) = 0.42, p < 0.001) and shorter sleep onset latency (d = 0.27, p <  0.001) from pre- to post-intervention. For insomnia, this effect was maintained at 1-year follow-up (OR = 0.54, p = 0.020). However, no effect of GCBT on sleep outcomes was found when comparing GCBT and WL. Also, no difference was found in sleep outcomes between brief and standard-length interventions. Adolescents defined as responders (i.e., having improved much or very much on anxiety after GCBT), did not differ from non-responders regarding sleep outcomes. Thus, anxiety-focused CBT, delivered in groups, showed no effect on sleep outcomes. Strategies specifically targeting sleep problems in adolescents should be included in GCBT when delivered as early intervention for adolescents with elevated anxiety.Trial registry Clinical trial registration: School Based Low-intensity Cognitive Behavioral Intervention for Anxious Youth (LIST); http://clinicalrials.gov/; NCT02279251, Date: 11.31. 2014


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P Dolati ◽  
M J Zamiri ◽  
A Akhlaghi ◽  
Z Jahromi

Abstract Study question Does quercetin (75 or 100 mg/kg BW/day) co-administration with lead acetate to male mice affects embryonic development in female mice? Summary answer The low-dose quercetin (75 mg/kg BW/day) ameliorated the adverse effects of lead acetate on mouse embryogenesis. What is known already Lead causes male infertility by impacting on endocrine system and spermatogenesis, and may exert undesirable effects on the offspring. The currently approved treatment for lead poisoning is the use of chelating agents, which form an insoluble complex with lead and shield it from biological targets; thus, reducing its toxicity. One of the main mechanisms of lead-induced toxicity is oxidative stress, and it has been reported that natural antioxidants can reduce the heavy metals toxicity. The aim of the present study was to examine the protective effects of quercetin on the toxicity induced by lead acetate on the embryogenesis in mice. Study design, size, duration Sexually mature (eight-week-old) NMRI male mice (n = 24) were randomly divided into four groups (n = 6 per group) receiving (i) distilled water (control group); (ii) lead acetate (150 mg/kg BW/day) dissolved in deionized water (LA); (iii) lead acetate (150 mg/kg BW/day) + quercetin (75 mg/kg BW/day) (LQ75); (IV) lead acetate (150 mg/kg BW/day) + quercetin (100 mg/kg BW/day) (LQ100). Treatments were applied daily as oral gavages for one cycle of the seminiferous epithelium (35 days). Participants/materials, setting, methods At the end of treatment administration, the males were joined with super-ovulated females, and the retrieved zygotes were cultured for evaluation of the embryo development (at 2-cell, 4-cell, 8-cell, and blastocyst stages), and blastocyst cell number using differential staining (propidium iodide and bisbenzimide). After incubation of capacitated sperm with oocytes, an ultraviolet light microscope was used following 3 min incubation with 25 µg⁄mL bisbenzamide solution for fertilization assessment. Main results and the role of chance Lead acetate (LA) treatment of male mice decreased the 2-cell stage compared with the control group (P &gt; 0.05). There was no difference between control and LQ75, and between LA and LQ100. The other stages of embryonic development were not significantly affected by the treatment. Overall, early embryonic development in the control and LQ75 mice were better than LQ100 and LA mice. The number of cells in the trophectoderm and inner-cell mass were not affected by treatments. However, the total blastocyst cell number in the control was higher than in the other groups; there was no significant difference between LQ100, LQ75 and LA groups. Fertilization rate was not affected by the treatments (P &lt; 0.05). Quercetin acts as a potent antioxidant at low doses, but at high doses exerts a pro-oxidant action. According to previous reports, higher concentrations of quercetin increased apoptosis and necrosis while decreasing the activities of the antioxidant enzymes. Also, it has been suggested that quercetin might disrupt the endocrine system and interfere with Sertoli cell function and sperm motility. Limitations, reasons for caution A limitation of this study is narrow dose selection; more studies are needed to determine the effective dose of quercetin in ameliorating the lead toxicity. There are also side effects of lead-quercetin chelates such as metal redistribution, essential metal loss, accumulation and persistency in intracellular sites, and peroxidation. Wider implications of the findings: Lead administration adversely impacted on the embryogenesis; on the other hand, paternal quercetin co-administration somewhat ameliorated the adverse effects of lead on mice embryogenesis. Trial registration number Not applicable


2018 ◽  
Vol 38 (4) ◽  
pp. 409-418 ◽  
Author(s):  
F Sadeghzadeh ◽  
MS Mehranjani ◽  
M Mahmoodi

Background: Dexamethasone (DEX) is a common medicine that is capable of causing malformation in the male reproductive system. The aim of this study was to investigate the effect of vitamin C (Vit-C) on spermatogenesis indexes and daily sperm production (DSP) in adult mice treated with DEX. Methods: Male Naval Medical Research Institute (NMRI) mice were divided into four groups: Control, DEX (7 mg/kg/day), Vit-C (100 mg/kg/day), and DEX +Vit-C and treated for 7 days with intraperitoneal injection. Results: A significant increase in the mean levels of serum and tissue malondialdehyde (MDA) and apoptosis of Leydig cells was found in the DEX group compared to the control group. Sperm motility, DSP, tubular differentiation index, meiotic index, spermatogenesis index, the mean number of spermatocytes, round and long spermatids, and Leydig cells, and also serum testosterone level decreased in the DEX group compared to the control group. The results of this study indicate that Vit-C can significantly prevent the adverse effects of DEX on the mean number of spermatocyte, spermatid, and Leydig cells, tubular differentiation, meiotic and spermatogenesis index, DSP, sperm motility, and the mean levels of serum MDA. Conclusion: In conclusion, our results showed that coadministration of Vit-C and DEX prevents the adverse effects of DEX on the spermatogenesis indexes and DSP.


Author(s):  
Genaro Gabriel Ortiz ◽  
Luis Humberto De Loera Rodríguez ◽  
Paloma Rivero Moragrega ◽  
Irma Ernestina Velázquez Brizuela ◽  
Juan Francisco Santoscoy Gutiérrez ◽  
...  

Background: Patients with cervical cancer (CC) receiving chemotherapy and radiotherapy have several gastrointestinal adverse effects. Objective: To evaluate the effect of dietary symbiotic supplementation on fecal calprotectin, bacterial DNA levels, and gastrointestinal adverse effects in patients with CC. Methods: Clinical, controlled, randomized, double-blind trial. Patients consumed symbiotics or placebo three times a day for 7 weeks. Fecal calprotectin was assessed by Elisa method. DNA from probiotic and pathogenic bacteria were determined by quantitative real-time polymerase chain reaction. Diarrheal evacuations were evaluated with the Bristol scale and nausea and vomiting were measured using the scale of the National Institute of Cancerology of the United States. Results: Fecal calprotectin concentration was lower in the symbiotic group compared to the control group (p <0.001). The concentrations and total proportions of the probiotic and pathogenic bacteria were similar in both groups. Nausea cases significantly diminished in both groups (p <0.001) at the end of the trial. Furthermore, the symbiotic group had a statistically significant decrease in the frequency and intensity of vomiting when compared to the control group (p <0.001). Conclusions: The symbiotic treatment decreases significantly the fecal calprotectin levels and the frequency and intensity of vomiting in patients with CC. KEYWORDS: faecal calprotectin, cervical cancer, symbiotic, qPCR.


2019 ◽  
Vol 18 (1) ◽  
pp. 50-54
Author(s):  
S. E. Gostischeva ◽  
N. V. Abzaeva ◽  
E. L. Rakitina ◽  
D. G. Ponomarenko ◽  
M. V. Kostuchenko ◽  
...  

Research objective–studying of a possibility of application antigen – stimulated cellular in vitro tests and technology of the cytometric analysis for control of immunogene activity of batches of vaccine plague live.Materials and methods.As biomodels used white laboratory mice, immunized commercial medicine of vaccine of the plague NIIEG line, live from a strain of Yersinia pestis EV, in doses – 8 х 102, 4 х 103, 2 х 104 and 1 х 105 of living microbic cells. Blood for a research was taken from intact mice and on 7, 14 and 21 days after immunization. The intensity of an antigenreaktivnost of lymphocytes was defined in cellular in vitro tests, analyzing a marker of early activation (CD45+CD3+CD25+) of lymphocytes with use of the monoclonal antibodies conjugated from fluorokhroma. As specific antigen used a complex of water-soluble antigens of a plague microbe.Results.As a result of a research it is shown that at the animals vaccinated by doses 4 х 103 – 1 х 105 living microbic cells, the highest level of an expression activation marker lymphocytes at anti-gene stimulation of in vitro is registered on 14 days after immunization, at the same time the quantity of CD25 – positive lymphocytes are on average 6.8 times higher, than in control group. High degree of direct link (coefficient of correlation of r = 1,000) quantities of the survived animals with increase in level of lymphocytes, expressiruyushchy markers of early activation – CD25 is established.Conclusions.The offered technique can be used as the additional test when studying degree of immunogenicity of new (kandidatny) vaccines against plague.


2021 ◽  
Vol 15 ◽  
Author(s):  
German Nacher-Soler ◽  
Sébastien Lenglet ◽  
Marta Coelho ◽  
Aurélien Thomas ◽  
François Voruz ◽  
...  

Cisplatin is a lifesaving chemotherapeutic drug with marked ototoxic adverse effects. Cisplatin-induced hearing loss affects a significant part of cancer-surviving patients and is an unmet clinical need with important socioeconomic consequences. Unfortunately, in current preclinical animal models of cisplatin ototoxicity, which are mainly based on systemic delivery, important morbidity is observed, leading to premature death. This methodology not only raises obvious animal welfare concerns but also increases the number of animals used in ototoxicity studies to compensate for dropouts related to early death. To overcome these important limitations, we developed a local delivery model based on the application of a cisplatin solution directly into the otic bulla through a retroauricular approach. The local delivery model reliably induced significant hearing loss with a mean threshold shift ranging from 10 to 30 dB, strongly affecting the high frequencies (22 and 32 kHz). Importantly, mice did not show visible stress or distress indicators and no significant morbidity in comparison with a traditional systemic delivery control group of mice injected intraperitoneally with 10 mg/kg cisplatin, where significant weight loss &gt;10% in all treated animals (without any recovery) led to premature abortion of experiments on day 3. Mass spectrometry confirmed the absence of relevant systemic uptake after local delivery, with platinum accumulation restricted to the cochlea, whereas important platinum concentrations were detected in the liver and kidney of the systemic cisplatin group. A clear correlation between the cochlear platinum concentration and the auditory threshold shift was observed. Immunohistochemistry revealed statistically significant loss of outer hair cells in the basal and apical turns of the cochlea and an important and statistically significant loss of auditory neurons and synapses in all cochlear regions. In conclusion, local cisplatin delivery induces robust hearing loss with minimal morbidity, thereby offering a reliable rodent model for human cisplatin ototoxicity, reducing the number of animals required and showing improved animal welfare compared with traditional systemic models.


REPORTS ◽  
2021 ◽  
Vol 2 (336) ◽  
pp. 54-60
Author(s):  
Zh. A. Zhonderbek ◽  
S. Zh. Kolumbayeva ◽  
A. V. Lovinskaya ◽  
N. Voronova

Increasing the body's resistance to various environmental pollutants' adverse effects is one of medicine's essential tasks. In this regard, an active search for antimutagens to eliminate or weaken mutagens' effect in the body is currently underway. One of the promising sources of antimutagenic compounds is the medicinal plant Rosa majalis Herrm (rosehips). The genotoxic and antigenotoxic activity of rosehips was studied on cells of bone marrow, spleen, liver, and kidneys of laboratory mice using an alkaline variant Comet assay. It was found that rosehip infusions in various concentrations (infusion, diluted infusion and herbal tea) do not have a genotoxic effect on the cells of the studied organs of laboratory animals. The medicinal rosehip's combined action with classical mutagen MMS significantly reduced (p<0.01) MMS-induced mutagenesis level. The various rosehip infusions used did not show statistically significant differences among themselves. The results obtained indicate the antigenotoxic activity of R. majalis infusions.


2003 ◽  
Vol 89 (5) ◽  
pp. 695-703 ◽  
Author(s):  
Maxine Bonham ◽  
Jacqueline M. O'Connor ◽  
H. Denis Alexander ◽  
James Coulter ◽  
Paula M. Walsh ◽  
...  

As a result of evidence documenting harmful effects of Zn supplementation on immune function and Cu status, thirty-eight men were recruited onto a Zn supplementation trial. The aim was to examine the effects of chronic Zn supplementation on circulating levels of peripheral blood leucocytes and lymphocyte subsets. Subjects (n 19) took 30 mg Zn/d for 14 weeks followed by 3 mg Cu/d for 8 weeks to counteract adverse effects, if any, of Zn supplementation on immune status resulting from lowered Cu status. A control group (n 19) took placebo supplements for the duration of the trial. Dietary intakes of Zn approximated 10 mg/d. Blood samples, taken throughout the trial, were assessed for full blood profiles and flow cytometric analyses of lymphocyte subsets. Putative indices of Cu status were also examined. Results indicate that there was no effect of Zn supplementation on circulating levels of peripheral blood leucocytes or on lymphocyte subsets. Cu status was also unaltered. Independent of supplement, there appeared to be seasonal variations in selected lymphocyte subsets in both placebo and supplemented groups. Alterations in circulating levels of B cells (cluster of differentiation (CD) 19), memory T cells (CD45RO) and expression of the intracellular adhesion molecule-1 (CD54) on T cells were observed. Findings indicated no adverse effects of Zn supplementation on immune status or Cu status and support the US upper level of Zn tolerance of 40 mg/d. The seasonal variations observed in lymphocyte subsets in the group as a whole could have implications for seasonal variability in the incidence of infectious diseases.


2018 ◽  
Vol 96 (8) ◽  
pp. 830-838 ◽  
Author(s):  
Modinat Adebukola Adefisayo ◽  
Wale Johnson Adeyemi ◽  
Quadri Kunle Alabi

Although cisplatin is a potent anticancer drug, it instigates oxidative and pro-inflammatory reactions that pose significant and distressing clinical symptoms. Therefore, this study investigated the effects of vitamin C and (or) l-carnitine on cisplatin-induced gastric mucosa damage in rat. The rats were allocated into 6 groups (n = 5). The control group received distilled water, while the treatment groups received cisplatin alone (CIP), or cisplatin with vitamin C, l-carnitine, or their combination. Cisplatin caused disruption of the gastric mucosa histoarchitecture and altered the mucus barrier function. Moreover, the stomach tissue of the CIP-treated group showed increased levels of oxidative stress markers (malondialdehyde and H2O2) and decreased activities of antioxidant (superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase) and non-antioxidant (reduced glutathione) enzymes. These deleterious events were accompanied with significant increases in pro-inflammatory cytokines and inflammatory infiltration markers, myeloperoxidase and inducible nitric oxide synthase. However, the administration of both vitamin C and l-carnitine, and not either of the two showed additive effects in attenuating the adverse effects of cisplatin. The histological results agreed with the biochemical assays. The study concluded that the combined administration of vitamin C and l-carnitine, but not the single therapy, could prevent the adverse effects of cisplatin on gastric tissue.


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