Last Day Of Treatment Research Articles

Effects of Achillea tenuifolia Lam. hydro-alcoholic extract on anxiety-like behavior and reproductive parameters in rat model of chronic restraint stress.

Achillea tenuifolia Lam (AT) has several biological activities and medicinal properties. In this study, we elucidated the impact of the AT on anxiety-related behaviors, reproductive parameters, antioxidant capacity in male rats subjected to chronic restraint stress (CRS). 35 Wistar rats were divided into five groups: control, CRS-control (received normal saline) and three CRS-treated groups received AT extract (100, 150, and 200 mg/kg body weight) for 21 consequences days. To induce CRS rats, the rats were immobilized for 21 days and received the extract orally. On the last day of treatment, anxiety-related behaviors were assessed through the sucrose preference test (SPT) as well as elevated plus maze (EPM) tests. Corticosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), testosterone levels were evaluated to determine reproductive capacity. Sperm parameters including the total count, motility, and viability were also analyzed. Weight of body, testis and seminal vesicles was measured as well. The findings revealed that 100, 150, and 200 mg/kg of AT extract had anxiolytic effects in CRS rats, as confirmed by the EPM test and SPT. In addition, AT extract could improve fertile capacity and sperm quality to varying degrees. The level of corticosterone had decreased, whereas the level of LH, FSH and testosterone had increased in CRS-treated rats. Moreover, the reduced level of MDA coincided with an increased rate of antioxidant capacity. Our findings suggest that AT extract could alleviate stress-induced dysfunctions. Overall, these observations would infer that AT extract could improve fertility capacity and behavioral impairment in the stress conditions. Assumption pathway describing the probability underlying mechanism of CRS-induced anxiety and reproductive toxicity and protective effect of AT.

L-Arginine Supplementation Significantly Affects Plasma Metabolome in Healthy Adults with Cardiometabolic Risk Irrespectively of Their Response to a Challenge Meal

Abstract Objectives We aimed to characterize the effects of a low dose of a sustained-release L-arginine (L-ARG) supplementation on plasma metabolome in healthy overweight adults with cardiometabolic risk factors, and study if its effect could improve the capacity to handle a high fat-high sugar meal, that deeply and acutely challenge metabolic capacities. Methods In a randomized, double-blind, controlled trial, 33 healthy overweight adults (BMI > 25kg/m²) with cardiometabolic risk (plasma triglycerides > 150 mg/dL; waist circumference > 94 cm (men) or > 80 cm (women)) were treated with 1.5 g L-ARG 3 times/d (4.5 g/d) or placebo for 4 weeks. On the last day of treatment, the volunteers consumed a high fat, high sugar meal challenge (900 kcal). Plasma was collected at fasting and 2, 4 and 6 h after the meal. Metabolites were analyzed by high-resolution mass spectrometry hyphenated to liquid chromatography, using reversed and normal phase columns, and operated in both positive and negative ionization modes. Annotation was performed using an in-house database referencing more than 1300 metabolites. Metabolic profiles were analyzed using Linear Mixed Models-PCA (LiMM-PCA), which enables to analyze repeated multivariate data. LiMM-PCA combines linear mixed models and PCA to assess the effects of both fixed factors (Treatment, Time before and after meal, interaction Treatment x Time, Order of treatment administration and Period of the study) and random factors (Individual). Results 521 metabolic features were identified in the plasma. Time accounted for most part of the variance in dataset (30.0%, P < 0.001), showing that the challenge meal leaved the largest imprint on the metabolome, with a clear distinction between fasting and fed states. In contrast, interindividual variability explained 10.1% of the total variance. L-ARG treatment significantly affected plasma metabolome (P < 0.001), explaining 0.6% of the variance. This effect did not differ after the challenge meal (time–treatment interaction, P > 0.10). The analysis of the metabolites contributing the most to these effects is under progress. Conclusions L-ARG supplementation has a significant effect on the metabolome in a situation where the metabolome is heavily impacted by a large allostatic load, and these two effects are independent of each other. Funding Sources Supported by a grant from Pierre Fabre Research Institute.

Sustained escitalopram administration affects glucose metabolism in the rat brain

Escitalopram is a selective serotonin reuptake inhibitor (SSRIs) antidepressant, drug that is currently used as first-line agents for the treatment of depression and it is also used in the treatment of other psychiatric disorders. The main goal of this study was to identify which brain areas are affected by escitalopram administration. This study was carried out on male Wistar rats that received escitalopram daily over 14 days and that were studied by 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG)-PET on the last day of treatment. Computed tomography (CT) images were acquired immediately before each PET scan and the main effects of drug administration were elucidated by Statistical Parametric Mapping. The results obtained indicated that repeated exposure to escitalopram increased metabolic activity in the retrosplenial and posterior cingulate cortices, while it decreased such activity in the ventral hippocampus, cerebellum, brainstem and midbrain regions, including the raphe nuclei and ventral tegmental area. Therefore, repeated exposure to escitalopram alters the activity of several brain areas closely related to the serotonergic system, and previously identified as key regions in the antidepressant effect induced by SSRIs. Furthermore, some of the changes found, such as the dampened metabolism in the ventral tegmental area, are similar to changes that have been described after treating with other fast-acting antidepressant approaches.

Postpartum corticosterone and fluoxetine shift the tryptophan-kynurenine pathway in dams

Perinatal depression (PND) affects 15% of mothers. Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line of treatment for PND but are not always efficacious. Previously, we found significant reductions in plasma tryptophan concentrations and higher hippocampal proinflammatory cytokine, IL-1β levels, due to maternal SSRI treatment. Both inflammation and tryptophan-kynurenine metabolic pathway (TKP) are associated with SSRI efficacy in individuals with major depressive disorder (MDD). TKP is divided into neuroprotective and neurotoxic pathways. Higher metabolite concentrations of the neurotoxic pathway are associated with depression onset and implicated in SSRI efficacy. Metabolites in TKP were investigated in a rodent model of de novo postpartum depression (PPD) given treatment with the SSRI, fluoxetine (FLX). Dams were administered corticosterone (CORT) (40 mg/kg, s.c.), and treated with the SSRI, fluoxetine (FLX) (10 mg/kg, s.c.), during the postpartum for 22 days after parturition. Plasma TKP metabolite concentrations were quantified on the last day of treatment. Maternal postpartum CORT increased neurotoxic metabolites and co-enzyme/cofactors in dams (3-hydroxykynurenine, 3-hydroxyanthranilic acid, vitamin B2, flavin adenine dinucleotide). The combination of both CORT and FLX shifted the neuroprotective-to-neurotoxic ratio towards neurotoxicity. Postpartum FLX decreased plasma xanthurenic acid concentrations. Together, our data indicate higher neurotoxic TKP expression due to maternal postpartum CORT treatment, similar to clinical presentation of MDD. Moreover, maternal FLX treatment showed limited efficacy to influence TKP metabolites, which may correspond to its limited efficacy to treat depressive-like endophenotypes in the postpartum. Overall suggesting changes in TKP may be used as a biomarker of de novo PPD and antidepressant efficacy and targeting this pathway may serve as a potential therapeutic target.

Influence of Supplementation of Lactoferrin, Melittin and Cecropin A to Rat Diet on Changes in Faecal Ammonia Concentrations, Short-Chain Fatty Acid Concentrations and Activities of Bacterial Enzymes.

Simple SummaryIn the present study conducted on Wistar laboratory rats, the effects of two selected insect antimicrobial peptides (AMPs), melittin and cecropin A, were investigated and compared to those attributed to well-known antibacterial action of lactoferrin. It was hypothesised that the dietary presence of lactoferrin, melittin or cecropin A strongly affects the rat large gut microbial activity at the time of protein/peptide administration and the durability of the effects may differ after their withdrawal from a diet. The experiment was conducted on living animals (without their euthanasia) and the dynamics of changes in pH, microbial enzyme activity, ammonia and short-chain fatty acids concentrations were investigated in the faeces during and after the dietary treatments with lactoferrin, melittin or cecropin A. The results suggested that the faecal intensity of microbial fermentation processes in rats was quickly reduced upon dietary addition of two AMPs and lactoferrin after two days of treatment, on average. The strongest suppression effect was observed on the 5th day of treatment and persisted on days 5–8. The changes caused by the supplemented lactoferrin and AMPs were reversible after 15 days, i.e., 10 days after the withdrawal of lactoferrin, melittin and cecropin A from the diet.We hypothesised that the dietary addition of the bioactive antimicrobial protein lactoferrin (LF) and peptides melittin (MT) or cecropin A (CR) at a dosage of 100 mg/kg to the diet of Wistar rats would result in strong modulatory effects on faecal microbial enzymatic activity, short-chain fatty acid and ammonia concentrations. To date, the changes in bacterial extracellular and intracellular enzymatic activities upon addition of dietary AMPs have not yet been studied. This experiment lasted 15 days; during the first 5 day period, the rats were fed the control diet (S) and diets supplemented with LF, MT or CR. On days 6–15, all rats were fed the control S diet. The faecal fermentation processes were substantially stopped after two days of treatment, on average, in all rats receiving LF and two AMPs. The deepest suppression effect was observed on the last day of treatment (day 5) and persisted through days 5–8. The highest decreases in faecal bacterial β-glucosidase and β-glucuronidase activities as well as in SCFA and ammonia concentrations were observed in the rats fed the CR diet. Only in the CR animals did the mechanism of suppressed microbial fermentation involve diminished enzyme release from bacterial cells to the digesta.

Multitarget Effect of 2-(4-(Methylthio)phenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-4-one in a Scopolamine-Induced Amnesic Rat Model.

Cholinergic system dysfunction, oxidative damage, and alterations in ion pump activity have been associated with memory loss and cognitive deficits in Alzheimer's disease. 1,3-thiazolidin-4-ones have emerged as a class of compounds with potential therapeutic effects due to their potent anticholinesterase activity. Accordingly, this study investigated the effect of the 2-(4-(methylthio)phenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-4-one (DS12) compound on memory, cholinergic and oxidative stress parameters, ion pump activity, and serum biochemical markers in a scopolamine-induced memory deficit model. Male Wistar rats were divided into four groups: I-Control; II-Scopolamine; III-DS12 (5mg/kg) + scopolamine; and IV-DS12 (10mg/kg) + scopolamine. The animals from groups III and IV received DS12 diluted in canola oil and administered for 7days by gavage. On the last day of treatment, scopolamine (1mg/kg) was administered intraperitoneally (i.p.) 30min after training in an inhibitory avoidance apparatus. Twenty-four hours after scopolamine administration, the animals were subjected to an inhibitory avoidance test and were thereafter euthanized. Scopolamine induced memory deficits, increased acetylcholinesterase activity and oxidative damage, and decreased Na+/K+-ATPase activity in cerebral cortex and hippocampus. Pretreatment with DS12 prevented these brain alterations. Scopolamine also induced an increase in acetylcholinesterase activity in lymphocytes and whereas butyrylcholinesterase in serum and treatment with DS12 prevented these changes. In animals treated with DS12, no changes were observed in renal and hepatic parameters when compared to the control group. In conclusion, DS12 emerged as an important multitarget compound capable of preventing neurochemical changes associated with memory deficits.

DNA methyltransferase- and histone deacetylase-mediated epigenetic alterations induced by low-level methylmercury exposure disrupt neuronal development.

Methylmercury (MeHg) is a chemical substance that causes adverse effects on fetal development. However, the molecular mechanisms by which environmental MeHg affects fetal development have not been clarified. Recently, it has been suggested that the toxic effects of chemicals on fetal development are related alterations in epigenetics, such as DNA methylation and histone modification. In order to analyze the epigenetic effects of low-level MeHg exposure on neuronal development, we evaluated neuronal development both in vivo and in vitro. Pregnant mice (C57BL/6J) were orally administrated 3mg/kg of MeHg once daily from embryonic day 12-14. Fetuses were removed on embryonic day 19 and brain tissues were collected. LUHMES cells were treated with 1nM of MeHg for 6days and collected on the last day of treatment. In both in vivo and in vitro samples, MeHg significantly suppressed neurite outgrowth. Decreased acetylated histone H3 (AcH3) levels and increased histone deacetylase (HDAC) 3 and HDAC6 levels were observed in response to MeHg treatment in both in vivo and in vitro experiments. In addition, increased DNA methylation and DNA methyltransferase 1 (DNMT1) levels were observed in both in vivo and in vitro experiments. The inhibition of neurite outgrowth resulting from MeHg exposure was restored by co-treatment with DNMT inhibitor or HDAC inhibitors. Our results suggest that neurological effects such as reduced neurite outgrowth due to low-level MeHg exposure result from epigenetic changes, including a decrease in AcH3 via increased HDAC levels and an increase in DNA methylation via increased DNMT1 levels.

Evaluation of the wound healing activity of the crude extract of root bark of Brucea antidysentrica, the leaves of Dodonaea angustifolia and Rhamnus prinoides in mice

BackgroundWounds are major problems of developing countries that can be managed alternatively using traditional medicinal plants. Since majority of currently available drugs for wound management are expensive and pose problems such as allergy and drug resistance, it is pivotal for the world to have intensified inquiries on the claimed medicinal plants to come up with wound healing chemicals being affordable, effective and safe. Ethiopian traditional healers recruit a wide range of medicinal plants with wound healing activities. Root bark juice of Brucea antidysentrica, the leaves of Rhamnus prinoides and Dodonaea angustifolia are claimed among others in the folklore medicine. Therefore, the aim of this study was to evaluate the in vivo wound healing activities of the root bark juice of Brucea antidysentrica, the leaves of Rhamnus prinoides and Dodonaea angustifolia in mice. MethodThe root bark juice of Brucea antidysentrica, the leaves of Rhamnus prinoides and Dodonaea angustifolia were collected, dried, ground to coarse powders. Then the crude extract was obtained by macerating with 80% methanol. The filtrate was dried, reconstituted in appropriate solvent and the wound healing activity was evaluated using excision and incision wound models. ResultsOn the last day of treatment, 80% methanol extracts from the selected medicinal plants showed a significant wound healing activity against control as supported by an increase in % wound contraction and a decrease in Epithelialization period. Ten percent of Rhamnus prinoides showed significant wound contraction against the control (P < 0.05) on days 2 and 4. But on day 6; except 5% extracts of Brucea antidysentrica and Rhamnus prinoides; all doses of extracts contracted the wound significantly (P < 0.05). Extracts of Dodonea angustifolia (5% & 10%) and 10% of Rhamnus prinoides and Bruceaantidysentrica increases wound contraction rate with increasing significant level on days 8 & 10 (P < 0.01) and 12 &14 (P < 0.001). Among the extracts, 10% of Dodonea angustifolia showed maximum percent (99.9%; P < 0.001) of wound contraction followed by 5% Dodonea angustifolia (99.15%; P < 0.001) and 10% Rhamnus prinoides (99.00%; P < 0.001) on the last day of treatment. In addition; significantly shorter healing time was attained by 5% &10% leaves of Dodonea angustifolia (P < 0.01), 10% leaves Rhamnus prinoides & root barks Brucea antidysentrica (P < 0.05). Ten percent of Rhamnus prinoides &Brucea antidysentrica (P < 0.05) and both doses (5% & 10%) of Dodonea angustifolia (P < 0.01) significantly increased the tensile strength by 54.10%, 56.58%, 63.04%, and 79.19%, respectively against the control. ConclusionThe 80% methanol crude extracts of the study plants support the traditional claims for healing of wounds as evidenced by an increase in wound contraction rate and tensile strength, decrease in Epithelialization period.

Cranberry (&lt;i&gt;Vaccinium macrocarpon&lt;/i&gt;) dietary supplementation and fecal microbiota of Wistar rats

Cranberry (Vaccinium macrocarpon) dietary supplementation can help prevention of urinary tract infections through the supply of proanthocyanidin-type polyphenols (PAC). The main uropathogenic bacteria are members of the intestinal microbiota. A randomized cross-over experiment was done to investigate whether cranberry dietary supplementation affects concentrations of thermotolerant coliforms, Enterococcus spp. and Lactobacillus spp. in rat faeces. Thirteen rats, housed in individual cages, received successively two diets as pellets during 7 days each: a standard diet without polyphenols and the standard diet supplemented with cranberry powder containing 10.9 mg/100 g of PAC. There was a 7 days wash-out period in between with standard diet without polyphenols. Body weight and feed intake were recorded. Faeces were collected on the last day of treatment, and crushed to count the different bacterial populations using the most probable number method. Thermotolerant coliforms were grown in BGBLB tubes and on MacConkey agar. Enterococcus spp. were grown in Rothe and Litsky broths and on KF Streptococcus agar. Lactobacillus spp. were grown in Man Rogosa Sharpe broth. Body mass gains were not affected by cranberry supplementation. This is consistent with equal food intake, cranberry powder not providing significant energy supplement. Cranberry dietary supplementation was associated with changes in fecal concentrations of thermotolerant coliforms, and Enterococcus spp. in some rats, but did not induce significant changes in bacterial fecal concentrations in a global population of 13 rats. In conclusion, we did not observe any significant effect of dietary cranberry supplementation on the fecal microbiota of Wistars rats for a 7-day diet.

Galactomannan Restore Letrozole Induced Polycystic Ovarian Syndrome (PCOS) in Rat Model

Current research aims towards evaluation of the effect of Galactomannan (GM) on letrozole-induced PCOS in adult female Wistar rats. Seven randomized groups of six female rats were made. The rats in all groups were administered with letrozole (1 mg/kg p.o.) for 21 days to induce PCOS. Rats in respective groups were treated with vehicle (10 ml/kg, p.o.), clomiphene citrate (1 mg/kg, p.o.), galactomannan (10, 20, 40 mg/kg, p.o.) and clomiphene citrate + galactomannan (1+20 mg/kg, p.o.) from day 22 to 36. On the last day of treatment i.e., 37th day of the study, blood was withdrawn, serum was separated and was used to assess hormonal and lipid profile. The rats were sacrificed in the late diestrus stage, ovaries were isolated and used for histopathological studies. Cysts in the ovaries of rats in control group was clearly seen after giving letrozole. Treatment either with Galactomannan or clomiphene citrate, significantly decreased blood sugar level, lipid profile, LH and testosterone whereas increased concentration of FSH and AMH was observed at the end of study. Reduced number of ovarian cysts as well as decreased body weight and ovary weight was documented for the possible protective role of galactomannan in PCOS. On the basis of results, galactomannan exerts protective effect in PCOS and could be given as adjuvant treatment with the available pharmacotherapy for the management of PCOS in women.

The Histologic Effect of Baclofen in Rat’s brain: An Experimental Study

Background: Baclofen is the only clinically available metabotropic GABAB receptor agonist. Several reports has been discussed the efficacy of baclofen but the available data on its effect of the behavior and brains' histology are still limited.Objectives: This work aims to assess the effects of long term exposure to baclofen (8weeks) on behavior and brains' histology in ratsMethods: Analysis of data of Twenty five healthy male Albino rats were performed. Rats weighing about 200–210 g with mean age of 65 days were randomly selected and categorized into three groups: Group 1(LD50 group): included five rats that gavaged with single dose of baclofen to test the LD50 of drug (145mg per Kg) .Group 2. (control group):included eight rats were gavaged with distilled water for 2 months. Group 3.(baclofen group): included 12 rats gavaged with 15mg/kg of baclofen (1/10th LD50) for 2 month. Behavioral Tests were conducted on all animals in group 2 and 3 including: Open-field test ,Open -field habituation task ,and object recognition(Novel) to examine the influence of drug on the cognition of rats. All animals were euthanized with ether after 24hours of last day of treatment. Brains were excised and collected from rats of group 2 and 3.Fixation of tissues was done using buffered solution of ten percent of formalin for twenty four hours with paraffin wax embedding. Sectioning and staining by hematoxylin and eosin protocol (H&E) and prepared to be examine histologically. To differentiate between the data of group 2 and 3 ,statistical analysis was performed by 1- way analysis of variance (ANOVA) .Least significant difference test with Duncan test was used . Value of P of equal or less than 0.05 means the difference is significant .Results: This study revealed that the rats of baclofen group traveled a greater total distance(in both sessions) when compared with those of control indicating their hyperactivity. The zone specific analysis showed that the rats that were administered with baclofen consumed markedly greater time nearby the walls in the peripheral part in the arena throughout the first and 2nd 15- min session in comparison with those of control group indicating the generalized hyperactivity and exploration. Rats of control group preferred the novel object in comparison with those of baclofen group. However there is no marked difference in the index of discrimination among rats of group 2 and 3. Histological sections of rats’ brains in group that were administered with 15mg/kg of baclofen for 2 month( baclofen group) revealed a diminished thickness in the pyramidal cells’ layer, irregular faintly stained cells with shrinkage in the some pyramidal nerve cells, dark staining cytoplasm and losing the characteristics of their nuclei.Conclusions:Chronic administration with baclofen (15mg/kg/day/2months) induces changes in the brain histology in rats, however, baclofen has no adverse effect on the behavior. To the best of our information, our work is the 1st that focus on the influence of baclofen on both the behavior and brains' histology. Our data suggesting that baclofen may have clinical utility.

Hypoglycemic, antidyslipidemic and antioxydant effects of Vitellaria paradoxa barks extract on high-fat diet and streptozotocin-induced type 2 diabetes rats

BackgroudVitellaria paradoxa is a plant belonging to the Sapotaceae family and used in traditional medicine in the treatment of diabetes mellitus. The aim of this work was to evaluate the hypoglycemic, antidyslipidemic and antioxidant effects of V. paradoxa on type 2 diabetic rats. MethodsTo induce type 2 diabetes mellitus (T2DM), animals were fed a high-fat diet for 4 weeks followed by an intraperitoneal injection of 35 mg/kg of streptozotocin. Diabetic rats were divided into groups and treated for 28 days with V. paradoxa extract (AEVP) at doses of 125, 250 and 500 mg/kg. Body weight, urine volume, food and water consumption were assessed at the start and end of treatment. The glucose tolerance test was performed on the last day of treatment. Blood samples were taken for the assay of biochemical parameters, organs (kidneys and liver) for markers of oxidative stress and pancreas for histological sections. ResultsAEVP (250 and 500 mg/kg) improved the drop in body weight, polyphagia, polydipsia and polyuria in diabetic rats. AEVP significantly reduced the concentrations of glucose, total cholesterol, triacylglycerol, urea, creatinine, activities of transaminases, and increased the levels of high density lipoprotein cholesterol and serum insulin. AEVP resulted in a decrease in malondialdehyde levels and an increase in catalase and superoxide dismutase activities. An increase in the size and number of islets in the pancreas has also been observed after administration of the extract. ConclusionAEVP has antidiabetic, antidyslipidemic and antioxidant properties, thus confirming its traditional use for the treatment of diabetes. These effects could be due to the presence of phytoconstituents, phenols and flavonoids presents in the plant extract.

Randomized Trial of Scrambler Therapy for Chemotherapy-Induced Peripheral Neuropathy: Crossover Analysis

ContextPreliminary trials report that Scrambler Therapy, a form of electroanalgesia, may improve discomfort from chemotherapy-induced peripheral neuropathy (CIPN). ObjectiveThe objective of this phase II, randomized controlled trial was to evaluate the efficacy of Scrambler therapy vs. transcutaneous electrical nerve stimulation (TENS) in treating CIPN. MethodsFifty patients were accrued for the first half of this two-part, crossover trial consisting of a 2-week treatment period with either Scrambler or TENS, followed by an 8-week observation period, and then crossover treatment. Twenty-two patients proceeded to the crossover phase. The primary means of assessment was patient-reported outcomes, including symptom severity scales and Global Impression of Change questionnaires. Symptoms were assessed daily during the treatment period and weekly during an 8-week observation period. ResultsA 50% or greater reduction in primary symptom (pain or tingling) score on the last day of treatment was achieved by 6 of 10 Scrambler-treated patients (60%) and 3 of 12 TENS-treated patients (25%) after crossover (P = 0.11). By day 4 of treatment, the two arms diverged with respect to mean change in primary symptom score; this effect was largely carried through to the end of the two-week treatment period. Similarly, Scrambler therapy appeared better than TENS when assessed by Global Impression of Change for neuropathy, pain, and overall quality of life. ConclusionsSimilar findings from the initial randomization and crossover phases of this study support further evaluation of the efficacy of Scrambler therapy in alleviating CIPN symptoms. Evaluation in a larger, randomized controlled trial with standardized treatment is warranted.

The Effect of Mangosteen Rind Extract (Garcinia mangostana L.) Toward Stress Oxidative Parameter, Leukocytes, Leukocytes Type Counts on Male Rats (Rattus norvegicus) with Excessive Physical Activity

BACKGROUND: Excessive and heavy physical activity could lead to the oxidative stress in the body. This condition can affect several blood parameters such as malondialdehyde (MDA), glutathione peroxidase (GPx), leukocytes, and its type counts. One way to overcome the effects of oxidative stress due to strenuous physical activity is by giving natural antioxidants. Mangosteen rind (Garcinia mangostana L.) contains considerable antioxidants, namely, xanthones and procyanidin.&#x0D; AIM: This research aimed to investigate the effect of mangosteen rind extract (MRE) on oxidative stress parameters, leukocyte count, and leukocyte count in male rats (Rattus norvegicus) that received excessive physical activity.&#x0D; METHODS: This study was purely experimental research with a post-test only control group design, using 29 white rats (R. norvegicus) as experimental animals, which were divided into four groups. The first group (P1) received distilled water and the other group received MRE at a dose of 50 mg/KgBW (Body Weight) (P2), 100 mg/KgBW (P3), and 200 mg/KgBW (P4) for 3 weeks, respectively. Swimming as a physical activity was carried out 3 times a week in all groups. Examination of leukocyte count and species was carried out on the last day of treatment after the rats swam to fatigue.&#x0D; RESULTS: MDA levels did not decrease significantly while GPx activity increased significantly. Moreover, the average leukocytes and lymphocytes showed a decrease but not significant. A significant decrease in the percentage of neutrophils and basophils was obtained by P4 group compared to others. In addition, a significant decrease in the average percentage of eosinophils for P3 and P4 groups was obtained. Furthermore, P3 and P4 group exhibit significant increase of the average percentage of monocytes.&#x0D; CONCLUSION: MRE as an antioxidant affects the levels of neutrophils, basophils, eosinophils, and monocytes but not in MDA, GPx, leukocytes, and lymphocytes.

Association between hospital anxiety and depression scale and problem‐related distress in patients with cancer in a Brazilian private institution

Emotional symptoms are frequently reported among patients with cancer. We evaluated the association between emotional symptoms and problem-related distress in a sample of patients with cancer about to initiate chemotherapy within a private hospital in Brazil. Patients were assessed before initiating chemotherapy, treatment mid-point, and on the last day of treatment for anxiety and depression (Hospital Anxiety and Depression Scale [HADS]) and for problem-related distress (Distress Thermometer Problem List). Problem-related distress variable was computed as the sum of practical, physical, spiritual and familial problems. Mixed-model analysis was applied to determine the association between HADS and problem-related distress, adjusting for age and gender. A total of 655 consecutive patients were enrolled. There was a significant main effect of time (F = 8.99, p = 0.0001), showing that emotional symptoms improve over time. A significant main effect was observed for problem-related distress (F = 371.56, p < 0.0001) revealing that patients with elevated problem-related distress at baseline tend to have higher HADS across the three time points, compared to patients with lower problem-related distress. There was an interaction effect between problem-related distress and time (F = 85.22, p < 0.0001), suggesting that HADS scores decreased differently over time, depending on patients' initial level of problem-related distress. Overall, emotional symptoms, while decreasing over time, remained associated with problem-related distress after chemotherapy in Brazil. The potential benefit of implementing a psychosocial intervention remains high throughout cancer treatment.

Feasibility and Initial Results of Daily Diffusion Weighted Imaging (DWI) Metrics Obtained during Stereotactic Body Radiation Therapy (SBRT) delivered using a 1.5 MR Linac

Changes in DWI metrics, specifically the apparent diffusion coefficient (ADC), of tumors following concurrent chemotherapy and radiation therapy (chemo-RT) were shown to correlate with clinical outcomes. Such changes have been primarily described in patients undergoing conventionally fractionated chemo-RT. DWI changes that occur following treatment with SBRT remain poorly understood. We sought to characterize changes in daily DWI metrics collected during the short course of SBRT, using a 1.5 MR Linac. Patients of various tumor sites undergoing SBRT on a 1.5 MR Linac were included. On each treatment day, patients had a fully quantitative DWI that was acquired during the time for daily treatment adaption. DWI was acquired using a single-shot spin echo EPI sequence (FOV: 380 mm2, matrix: 128x128, TE: 69 ms, TR: 5500 ms, four b-values ranging from 0 to 550 s/mm). Fat suppression, acceleration, and number of averages per b-value were optimized to maximize image quality and minimize geometric distortion. Gross tumor volumes (GTVs) were contoured daily by the attending physician using an image processing software. Distributions of ADC values for voxels contained in the GTV were used to determine imaging features including mean, median, kurtosis, skewness and standard deviation. Student’s t-test was used to compare tumor ADC values. Of 38 patients screened, 27 patients (17 males, 10 females) had daily DWI scans available for analysis. The median age was 68. Patients received total doses ranging from 24Gy to 60Gy and fraction number ranged from 3 to 6. 128 DWI scans were analyzed. Mean tumor ADCs ranged from 0.79 to 2.08, median ADCs ranged from 0.75 to 1.99, kurtosis ranged from -1.11 to 3.61, standard deviations ranged from 0.23 to 0.93 and skewness ranged from -0.86 to 1.36. The comparison of mean tumor ADC values measured on the first day of treatment to those measured on the last day of treatment failed to reveal a statistically significant difference (p = 0.087). 59% of patients had an increase in mean ADC at the time of delivery of the second fraction. That percentage was 63% at the third fraction, 80% at the fourth fraction and 75% at the fifth fraction. We characterized daily DWI metrics for patients undergoing SBRT using a 1.5 MR Linac. We observe measurable changes in certain image features (mean, median, kurtosis, standard deviation and skewness) of tumor ADC maps. Although there was no statistical difference between the mean ADC values measured at the first and last fractions, we noted that an increasing proportion of patients exhibits a favorable rise in mean or median tumor ADC throughout the course of SBRT. The ability to longitudinally track MRI metrics represents a novel potential biomarker of response to SBRT that warrants further investigation and correlation with clinical endpoints.

Kleinhovia hospita extract alleviates experimental hepatic and renal toxicities induced by a combination of antituberculosis drugs

Introduction: Antituberculosis drugs are associated with hepatic and renal toxicities due to drug’s radical metabolites. Kleinhovia hospita L extract possesses a potent antioxidant capacity that can be beneficial in eradication of oxidative-induced cell damage. This study aimed to evaluate the effects of K. hospita hydro-alcoholic extract on biomarkers and structure changes in liver and kidney induced by a combination of antituberculosis drugs (CAD), comprising isoniazid, rifampicin, pyrazinamide and ethambutol in Wistar rats. Methods: Thirty-five male Wistar rats were assigned into one of the five groups: control, CAD, and CAD with K. hospita extract in three different doses (125, 250 and 500 mg/kg). The extract was administered three hours prior to CAD and all treatments were carried out for 28 days. Following the last day of treatment, blood samples and organs were collected for biomarker analysis and histopathological examinations. Results: Twenty-eight days of CAD treatment in rats induced marked elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), serum creatinine and urea levels compared to controls. K. hospita extract at higher doses (250 mg/kg and 500 mg/kg) significantly improved ALT, urea and creatinine levels in the rats treated with CAD (P&lt;0.05), although it did not significantly reduce AST. Furthermore, liver and renal tissue damages induced by CAD were restored with K. hospita extract treatment, especially at higher doses. Conclusion: Kleinhovia hospita extract treatment has the potential to protect the liver and renal damage induced by toxic doses of CAD.

Aqueous ozone therapy improves the standard treatment of leishmaniasis lesions in animals leading to local and systemic alterations.

The current treatment of leishmaniasis presents some problems, such as cell toxicity, parenteral route, and time of treatment. Ozone emerges as an option to accelerate the standard treatment due to the immunomodulatory, antioxidant, and wound healing activity reported in the literature. This work aimed to evaluate the efficacy of aqueous ozone as an adjuvant to the standard treatment of cutaneous lesions caused by Leishmania amazonensis in an experimental model. For in vivo experiments, mice were randomly distributed in 6 groups, which were infected with L. amazonensis and treated in five different schedules using the standard treatment with Glucantime® with or without aqueous ozone. After the last day of treatment, the animals were euthanized and were analyzed: the thickness of lesions; collagen deposition, the parasitic burden of the lesions; blood leukocyte number; NO; and cytokine dosages and arginase activity from peritoneal macrophages. All treated groups showed a decrease in the lesion, but with a significative deposition of collagen in lesions with local ozone treatment. The parasite burden showed that ozone enhanced the leishmanicidal activity of the reference drug. The reduction of NO production and blood leukocyte count and increases in the arginase activity showed an immunomodulatory activity of ozone in the treated animals. Thus, ozone therapy has been shown to work as an adjuvant in the treatment of Leishmania lesions, enhancing leishmanicidal and wound healing activity of standard treatment.

A Patient's Perspective: Bridging the Transition Following Radiation Therapy for Patients with Breast Cancer

IntroductionAs the number of women surviving breast cancer grows, it becomes increasingly important to investigate their unique psychosocial and physical needs in the post-treatment period. The period of transition from patient to survivor is a time fraught with physical and emotional challenges. This qualitative study was conducted to gain insight into the perspective of breast cancer patients transitioning to survivorship after receiving RT in Alberta. MethodsTen patients receiving radiation therapy (RT) for breast cancer in Alberta participated in an open-ended telephone interview two to three weeks following the cessation of treatment. The data was analyzed using a qualitative interpretive phenomenological approach. Data was clustered and categorized, and emerging themes were examined. ResultsThough participants reported to be satisfied with the care and information they received, a need for more robust and detailed skin care education was identified. Patients expressed a sense of anxiety around returning to normalcy following RT, and described feeling lonely, and unsure of themselves in the post-treatment period. A post-treatment phone call may allow Radiation Therapists (RTTs) to mitigate the ongoing needs of patients in the period between their last day of treatment and their first follow-up visit. ConclusionThis project has given us an opportunity to hear the voice of the patient, thus laying the groundwork to allow for a more patient-centred approach to the transition of care following RT. The data gathered suggests possible areas for development of interventions and supports for breast cancer patients as they transition into survivorship.

What tomorrow will bring: Expectations for the next day predicting the cortisol awakening response in young adults

Perinatal depression (PND) affects 15% of mothers. Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line of treatment for PND but are not always efficacious. Previously, we found significant reductions in plasma tryptophan concentrations and higher hippocampal proinflammatory cytokine, IL-1β levels, due to maternal SSRI treatment. Both inflammation and tryptophan-kynurenine metabolic pathway (TKP) are associated with SSRI efficacy in individuals with major depressive disorder (MDD). TKP is divided into neuroprotective and neurotoxic pathways. Higher metabolite concentrations of the neurotoxic pathway are associated with depression onset and implicated in SSRI efficacy. Metabolites in TKP were investigated in a rodent model of de novo postpartum depression (PPD) given treatment with the SSRI, fluoxetine (FLX). Dams were administered corticosterone (CORT) (40 mg/kg, s.c.), and treated with the SSRI, fluoxetine (FLX) (10 mg/kg, s.c.), during the postpartum for 22 days after parturition. Plasma TKP metabolite concentrations were quantified on the last day of treatment. Maternal postpartum CORT increased neurotoxic metabolites and co-enzyme/cofactors in dams (3-hydroxykynurenine, 3-hydroxyanthranilic acid, vitamin B2, flavin adenine dinucleotide). The combination of both CORT and FLX shifted the neuroprotective-to-neurotoxic ratio towards neurotoxicity. Postpartum FLX decreased plasma xanthurenic acid concentrations. Together, our data indicate higher neurotoxic TKP expression due to maternal postpartum CORT treatment, similar to clinical presentation of MDD. Moreover, maternal FLX treatment showed limited efficacy to influence TKP metabolites, which may correspond to its limited efficacy to treat depressive-like endophenotypes in the postpartum. Overall suggesting changes in TKP may be used as a biomarker of de novo PPD and antidepressant efficacy and targeting this pathway may serve as a potential therapeutic target.