Social Interaction in Adolescent Rats with Neonatal Ethanol Exposure: Impact of Sex and CE-123, a Selective Dopamine Reuptake Inhibitor.

Children with fetal alcohol spectrum disorders (FASDs) demonstrate deficits in social functioning that contribute to early withdrawal from school and delinquency, as well as the development of anxiety and depression. Dopamine is involved in reward, motivation, and social behavior. Thus, we evaluated whether neonatal ethanol exposure (in an animal model of FASDs) has an impact on social recognition memory using the three-chamber social novelty discrimination test during early and middle adolescence in male and female rats, and whether the modafinil analog, the novel atypical dopamine reuptake inhibitor CE-123, can modify this effect. Our study shows that male and female rats neonatally exposed to ethanol exhibited sex- and age-dependent deficits in social novelty discrimination in early (male) and middle (female) adolescence. These deficits were specific to the social domain and not simply due to more general deficits in learning and memory because these animals did not exhibit changes in short-term recognition memory in the novel object recognition task. Furthermore, early-adolescent male rats that were neonatally exposed to ethanol did not show changes in the anxiety index but demonstrated an increase in locomotor activity. Chronic treatment with CE-123, however, prevented the appearance of these social deficits. In the hippocampus of adolescent rats, CE-123 increased BDNF and decreased its signal transduction TrkB receptor expression level in ethanol-exposed animals during development, suggesting an increase in neuroplasticity. Thus, selective dopamine reuptake inhibitors, such as CE-123, represent interesting drug candidates for the treatment of deficits in social behavior in adolescent individuals with FASDs.

Can the supplementation of vitamin D, sun exposure, and isolation during the COVID-19 pandemic affect the seasonal concentration of 25(OH)D and selected blood parameters among young soccer players in a one-year training season?

OBJECTIVE: This study examined the effect of vitamin D supplementation, sunlight radiationradiation, and home isolation during the COVID-19 pandemic on the seasonal changes in 25(OH)D concentration and selected biomarkers in young soccer players along a one-year training cycle. METHOD: Forty elite young soccer players (age: 17.2 ± 1.16 years, body mass: 70.2 ± 5.84, and body height: 179.1 ± 4.26 cm) participated in the research. Only 24 players completed the measurements during all four time- points (T1-: September 2019, T2-: December 2019, T3-: May 2020, and T4-: August 2020) and were divided into two subgroups: supplemented group (GS) and placebo group (GP). Players from GS received 5,000 IU of vitamin D for 8 weeks (January-MarchJanuary-March 2020). Several biomarkers such as 25(OH)D, white blood cells (WBC), red blood cells (RBC), hemoglobin (HGB), muscle damage markersmarkers, and lipid profile were measured. RESULTS: AnalysisThe analysis of the total group demonstrated significant seasonal changes in 25(OH)D, HGB, asparagine aminotransferaseaminotransferase, and creatine kinase along the one1-year training cycle. The level of 25(OH)D concentrationinconcentration in T4 was significantly (p < 0.001, pη [ = 0.82) higher in both subgroups in comparison to T2 and T3. Moreover, the significant (p = 0.023) but poor (r = -0.23) correlation between 25(OH)D and WBC was calculated. CONCLUSION: Current research confirmed the significant seasonal changes in 25(OH)D concentration during four seasons. 8-weekEight-week vitamin D supplementation had no extended effect on the level of 25(OH)D concentration.

The Level of Selected Blood Parameters in Young Soccer Players in Relation to the Concentration of 25(OH)D at the Beginning and End of Autumn.

This study aimed to demonstrate the changes of selected blood parameters in relation to 25(OH)D concentration during the autumn period in young soccer players. A total of 35 participants' results (age: 17.5 ± 0.6 years, body mass 71.3 ± 6.9 kg) were tested twice: in mid-September and in mid-December and divided into subgroups with regard to two criteria. First, according to the initial level of the 25(OH)D concentration (optimal group­ODG, suboptimal group­SDG), second, according to drops in 25(OH)D concentration (high drop group­HDG, low drop group­LDG). A significant decrease (p < 0.001) in the 25(OH)D concentration was reported in the total group (TGr) and in all subgroups. Blood parameters such as white blood cells, red blood cells, haemoglobin and haematocrit increased significantly (p < 0.05) in TGr during the analysed period of time. The analysis of changes in the lipid profile did not expose significant differences except triglycerides. The asparagine amino transferase and creatine kinase activity decreased significantly after autumn in all analysed groups. The declining level of 25(OH)D concentration should be compensated (e.g., with vitamin D supplementation) during autumn. Applied training loads could also influence the blood parameters variability in young soccer players. Regular measurements of 25(OH)D concentration are helpful in identifying potential drops and allows for the preparation of individual supplementation plans for the players.

Cocaine-Induced Time-Dependent Alterations in Cytochrome P450 and Liver Function.

Cytochrome P450 is responsible for the metabolism of endogenous substrates, drugs and substances of abuse. The brain and nervous system regulate liver cytochrome P450 via neuroendocrine mechanisms, as shown in rodents. Cocaine exerts its addictive effects through the dopaminergic system, the functioning of which undergoes changes during its continuous use. Therefore, it can be hypothesized that the regulation of cytochrome P450 by cocaine may also alter during the addiction process, cessation and relapse. We analyzed preclinical studies on the mechanisms of the pharmacological action of cocaine, the role of the brain's dopaminergic system in the neuroendocrine regulation of cytochrome P450 and the in vitro and in vivo effects of cocaine on the cytochrome P450 expression/activity and hepatotoxicity. The results of passive cocaine administration indicate that cocaine affects liver cytochrome P450 enzymes (including those engaged in its own metabolism) via different mechanisms involving the expression of genes encoding cytochrome P450 enzymes and interaction with enzyme proteins. Thus, it may affect its own oxidative metabolism and the metabolism of endogenous substrates and other co-administered drugs and may lead to hepatotoxicity. Its effect depends on the specific cytochrome P450 enzyme affected, cocaine dosage, treatment duration and animal species. However, further complementary studies are needed to find out whether cocaine affects cytochrome P450 via the brain's dopaminergic system. The knowledge of cocaine's effect on cytochrome P450 function during the entire addiction process is still incomplete. There is a lack of information on the enzyme expression/activity in animals self-administering cocaine (addicted), in those withdrawn after cocaine self-administration, and during relapse in animals previously addicted; furthermore, there is no such information concerning humans. The subject of cytochrome P450 regulation by cocaine during the addiction process is an open issue, and addressing this topic may help in the treatment of drug abuse patients.

Evaluation of the 5-HT2C receptor drugs RO 60-0175, WAY 161503 and mirtazepine in a preclinical model of comorbidity of depression and cocaine addiction.

BACKGROUND: Epidemiological data indicate a high rate of comorbidity of depression and cocaine use disorder (CUD). The role of serotonin 2C (5-HT2C) receptors in the mechanisms responsible for the coexistence of depression and CUD was not investigated. METHODS: We combined bilateral olfactory bulbectomy (OBX), an animal model of depression, with intravenous cocaine self-administration and extinction/reinstatement in male rats to investigate two 5-HT2C receptor agonists (Ro 60-0175 (RO) and WAY 161503 (WAY)) and the 5-HT2C-receptor preferring antagonist mirtazapine (MIR; an antidepressant), with the goal of determining whether these drugs alter cocaine-induced reinforcement and seeking behaviors. Additionally, neurochemical analyses were performed following cocaine self-administration and its abstinence period in the brain structures in OBX rats and SHAM-operated controls. RESULTS: Acute administration of RO reduced, while WAY non-significantly attenuated cocaine reinforcement in both rat phenotypes. Moreover, RO or WAY protected against cocaine-seeking behavior after acute or after repeated drug administration during extinction training in OBX and SHAM rats. By contrast, acutely administered MIR did not alter cocaine reinforcement in both rat phenotypes, while it's acute (but not repeated) pretreatment reduced cocaine-seeking in OBX and SHAM rats. In neurochemical analyses, cocaine reinforcement increased 5-HT2C receptor levels in the ventral hippocampus; a preexisting depression-like phenotype enhanced this effect. The 10-daily cocaine abstinence reduced 5-HT2C receptor expression in the dorsolateral striatum, while the coexistence of depression and CUD enhanced local receptor expression. CONCLUSION: The results support a key role of 5-HT2C receptors for treating CUD and comorbid depression and CUD. They may be backs the further research of pharmacological strategies with drug targeting receptors.

The Effect of the Selective N-methyl-D-aspartate (NMDA) Receptor GluN2B Subunit Antagonist CP-101,606 on Cytochrome P450 2D (CYP2D) Expression and Activity in the Rat Liver and Brain.

The CYP2D enzymes of the cytochrome P450 superfamily play an important role in psychopharmacology, since they are engaged in the metabolism of psychotropic drugs and endogenous neuroactive substrates, which mediate brain neurotransmission and the therapeutic action of those drugs. The aim of this work was to study the effect of short- and long-term treatment with the selective antagonist of the GluN2B subunit of the NMDA receptor, the compound CP-101,606, which possesses antidepressant properties, on CYP2D expression and activity in the liver and brain of male rats. The presented work shows time-, organ- and brain-structure-dependent effects of 5-day and 3-week treatment with CP-101,606 on CYP2D. Five-day treatment with CP-101,606 increased the activity and protein level of CYP2D in the hippocampus. That effect was maintained after the 3-week treatment and was accompanied by enhancement in the CYP2D activity/protein level in the cortex and cerebellum. In contrast, a 3-week treatment with CP-101,606 diminished the CYP2D activity/protein level in the hypothalamus and striatum. In the liver, CP-101,606 decreased CYP2D activity, but not the protein or mRNA level, after 5-day or 3-week treatment. When added in vitro to liver microsomes, CP-101,606 diminished the CYP2D activity during prolonged incubation. While in the brain, the observed decrease in the CYP2D activity after short- and long-term treatment with CP-101,606 seems to be a consequence of the drug effect on enzyme regulation. In the liver, the direct inhibitory effect of reactive metabolites formed from CP-101,606 on the CYP2D activity may be considered. Since CYP2Ds are engaged in the metabolism of endogenous neuroactive substances, it can be assumed that apart from antagonizing the NMDA receptor, CP-101,606 may modify its own pharmacological effect by affecting brain cytochrome P450. On the other hand, an inhibition of the activity of liver CYP2D may slow down the metabolism of co-administered substrates and lead to pharmacokinetic drug-drug interactions.

Incorporation of Tumor-Free Distance and Other Alternative Ultrasound Biomarkers into a Myometrial Invasion-Based Model Better Predicts Lymph Node Metastasis in Endometrial Cancer: Evidence and Future Prospects.

Myometrial invasion (MI) is a parameter currently used in transvaginal ultrasound (TVS) in endometrial cancer (EC) to determine local staging; however, without molecular diagnostics, it is insufficient for the selection of high-risk cases, i.e., those with a high risk of lymph node metastases (LNM). The study's objective was to answer the question of which TVS markers, or their combination, reflecting the molecular changes in EC, can improve the prediction of LNM. Methods: The TVS examination was performed on 116 consecutive EC patients included in this prospective study. The results from the final histopathology were a reference standard. Univariate and multivariate logistic models of analyzed TVS biomarkers (tumor [T] size, T area [AREA], T volume [SPE-VOL], MI, T-free distance to serosa [TFD], endo-myometrial irregularity, [EMIR], cervical stromal involvement, CSI) were evaluated to assess the relative accuracy of the possible LNM predictors., Spline functions were applied to avoid a potential bias in assuming linear relations between LNM and continuous predictors. Calculations were made in R using libraries splines, glmulti, and pROC. Results: LNM was found in 20 out of the 116 (17%) patients. In univariate analysis, only uMI, EMIR, uCSI and uTFD were significant predictors of LNM. The accuracy was 0.707 (AUC 0.684, 95% CI 0.568−0.801) for uMI (p < 0.01), 0.672 (AUC 0.664, 95% CI 0.547−0.781) for EMIR (p < 0.01), 0.776 (AUC 0.647, 95% CI 0.529−0.765) for uCSI (p < 0.01), and 0.638 (AUC 0.683, 95% CI 0.563−0.803) for uTFD (p < 0.05). The cut-off value for uTFD was 5.2 mm. However, AREA and VOL revealed a significant relationship by nonlinear analysis as well. Among all possible multivariate models, the one comprising interactions of splines of uTFD with uMI and splines of SPE-VOL with uCSI showed the most usefulness. Accuracy was 0.802 (AUC 0.791, 95% CI 0.673−0.91) Conclusions: A combination of uTFD for patients with uMI > 50%, and SPE-VOL for patients with uCSI, allows for the most accurate prediction of LNM in EC, rather than uMI alone.

Effect of Vitamin D3 Supplementation on Interleukin 6 and C-Reactive Protein Profile in Athletes.

Vitamin D3 has a preventive, anti-inflammatory effect. However, there are still few studies linking the effects of athlete training to vitamin D3 supplementation and the immune response. The study evaluated the impact of vitamin D3 supplementation on interleukin 6 (IL-6) release during physical exercise in relation to C-reactive protein (CRP) levels in healthy male athletes. Twenty-five soccer players were divided into two groups-with (GS) and without (GN) vitamin D3 supplementation in a dose of 20,000 IU twice a week for 8 wk (about 6,000 IU/d). At the baseline (T1) and at the end (T2) of the training cycle serum concentrations of 25-hydroxyvitamin D [25(OH)D], IL-6 and CRP were measured. In the GS group, we observed a significant increase in 25(OH)D concentration (p=0.004), and non-significantly increased levels (p>0.05) of IL-6 and CRP. At the baseline, CRP in the supplemented athletes who had suboptimal vitamin D3 concentration in T1 (GSO) was significantly higher than in those with an optimal baseline vitamin D3 level (GO) (p=0.028). However, in GO in T2, a non-significant trend of negative correlation (p=0.055) between 25(OH)D concentration and IL-6 level was found. In the total study group (TG), a statistically significant (p=0.021) negative correlation in T1 was observed between 25(OH)D and CRP. However, our results do not support the immune-modulatory effect of vitamin D3 supplementation in a dose of 6,000 IU/d in athletes, in relation to IL-6 production and its subsequent stimulatory effect on CRP releasing.

Increased density and antagonistic allosteric interactions in A2AR-D2R heterocomplexes in extinction from cocaine use, lost in cue induced reinstatement of cocaine seeking.

Neurochemical studies were previously performed on the effects of a 10 day extinction learning from cocaine self-administration on D2R and A2AR recognition and D2R Gi/o coupling in the ventral striatum. In the present study biochemical receptor binding and proximity ligation assay were used to study possible changes in the allosteric receptor-receptor interactions and the density of the A2AR-D2R heterocomplexes in the ventral striatum (nucleus accumbens shell) in extinction from cocaine self-administration including cue induced reinstatement of cocaine seeking. A significant and clear-cut reduction of active lever pressing was observed in extinction on day 10 from cocaine use. In cue induced reinstatement of cocaine self-administration a significant return in active lever presses developed. In extinction, significant increases in the density of A2AR-D2R and D2R-Sigma1R heterocomplexes were observed in nucleus accumbens shell. In contrast, cue-induced reinstatement of cocaine seeking produced no significant changes in these heteroreceptor complexes of the nucleus accumbens shell. In the 3H raclopride/quinpirole competition binding experiments, the extinction led to a significant increase in the D2R Ki, High dissociation constant in the ventral striatum upon ex vivo exposure to CGS 21680 (100 nM), compared to the same exposure performed in membrane preparations from yoked saline rats. No significant changes in D2R Ki, High values were observed in membrane preparations from rats after cue-induced reinstatement of cocaine-seeking undergoing the same exposure ex vivo to CGS 21680 when compared with membrane preparations from yoked saline rats undergoing the same procedures. It seems likely that increased formation of A2AR-D2R and putative A2AR-D2R-Sigma1R heterocomplexes in the nucleus accumbens shell is part of the mechanism for the enhanced antagonistic allosteric A2AR-D2R interactions developed in extinction learning from cocaine. It reduces cocaine reward through reduced D2R function, and these inhibitory mechanisms are no longer in operation in cue induced reinstatement of cocaine seeking.

Changes of 25(OH)D Concentration, Bone Resorption Markers and Physical Performance as an Effect of Sun Exposure, Supplementation of Vitamin D and Lockdown among Young Soccer Players during a One-Year Training Season.

The main purpose of this research was to demonstrate the changes in 25(OH)D concentration, bone resorption markers, and physical fitness along the one-year training season in young soccer players. A total of 24 young soccer players (age: 17.2 ± 1.16 years, mass: 70.2 ± 5.84, height: 179.1 ± 4.26 cm) were tested at four different time points across one year (T1-September 2019; T2-December 2019; T3-May 2020; T4-August 2020). After T2 (during COVID-19 lockdown), players were divided into a supplemented (GS) group and a placebo group (GP). Variables such as 25(OH)D, calcium (Ca), phosphorus (P), parathyroid hormone (PTH), aerobic capacity, speed, and explosive power were measured. Analyses performed for all participants indicated significant changes in all selected blood markers and running speed. The highest values in 25(OH)D were noted during summertime in T1 and T4. After individuals were split into two groups, a two-factorial ANOVA demonstrated a significant time interaction for 25(OH)D, Ca, P, PTH, 30 m sprint, and counter-movement jump. Significant time x group effect was calculated for aerobic capacity. This study confirmed that 25(OH)D concentration varies between four seasons, with the greatest decreases in the low sunlight periods. Vitamin D supplementation did not cause a preventive and long-lasting effect of increasing the 25(OH)D concentration in the young soccer players.

The Selective NMDA Receptor GluN2B Subunit Antagonist CP-101,606 with Antidepressant Properties Modulates Cytochrome P450 Expression in the Liver.

Recent research indicates that selective NMDA receptor GluN2B subunit antagonists may become useful for the treatment of major depressive disorders. We aimed to examine in parallel the effect of the selective NMDA receptor GluN2B subunit antagonist CP-101,606 on the pituitary/serum hormone levels and on the regulation of cytochrome P450 in rat liver. CP-101,606 (20 mg/kg ip. for 5 days) decreased the activity of CYP1A, CYP2A, CYP2B, CYP2C11 and CYP3A, but not that of CYP2C6. The alterations in enzymatic activity were accompanied by changes in the CYP protein and mRNA levels. In parallel, a decrease in the pituitary growth hormone-releasing hormone, and in serum growth hormone and corticosterone (but not T3 and T4) concentration was observed. After a 3-week administration period of CP-101,606 less changes were found. A decrease in the CYP3A enzyme activity and protein level was still maintained, though no change in the mRNA level was found. A slight decrease in the serum concentration of corticosterone was also maintained, while GH level returned to the control value. The obtained results imply engagement of the glutamatergic system in the neuroendocrine regulation of cytochrome P450 and potential involvement of drugs acting on NMDA receptors in metabolic drug-drug interactions.

Treatment with dopamine ß-hydroxylase (DBH) inhibitors prevents morphine use and relapse-like behavior in rats.

BACKGROUND: Opioid use disorders are serious contributors to the harms associated with the drug use. Unfortunately, therapeutic interventions for opioid addicts after detoxification have been limited and not sufficiently effective. Recently, several studies have led to promising results with disulfiram (DSF), a dopamine ß-hydroxylase (DBH) inhibitor, showing that it is a potent agent against not only alcohol but also addiction to various drugs. MATERIALS AND METHODS: This study was designed to examine whether DSF and nepicastat (NEP; another DBH inhibitor) modify morphine intake and reinstatement of seeking-behavior using the rat model of intravenous morphine self-administration. Additionally, we intended to estimate the effects of both inhibitors on the locomotor activity as well as on extracellular dopamine and its metabolite levels in the nucleus accumbens using microdialysis in naive rats. RESULTS: We demonstrated that both DBH inhibitors reduced responding to morphine self-administration. Moreover, DSF and NEP administered acutely before reinstatement test sessions consistently attenuated the reinforcing effects of morphine and a morphine-associated conditioned cue. The observed effects for lower doses (6.25-25 mg/kg; ip) of both DBH inhibitors seem to be independent of locomotor activity reduction and dopamine level in the nucleus accumbens. Neither DSF nor NEP administered daily during morphine abstinence with extinction training sessions had any effect on active lever-responding and changed the reinstatement induced by morphine priming doses. Reinstatement of drug-seeking behavior induced by a conditioned cue previously associated with morphine delivery was attenuated following repeated administration of DSF or NEP during the abstinence period. CONCLUSION: These results seem to point to the significance  of DBH inhibition as a potential pharmacotherapy against morphine use disorders.

Gender differences in the association between physical activity and obesity in adults with vision and hearing losses.

BACKGROUND: Physical inactivity is strongly associated with obesity, which in turn is a major risk factor for many non-communicable diseases. We examined associations between physical inactivity and obesity in Spanish adults with vision and hearing difficulties and explored differences between men and women. METHODS: Data from the Spanish National Health Survey 2017 were analyzed [n = 23 089 adults (15-103 years, mean age 53.4 ± 18.9 years, 45.9% men)]. Participants self-reported difficulties in seeing and hearing. Physical inactivity (exposure) was evaluated with the International Physical Activity Questionnaire Short Form. Obesity (outcome) was defined as body mass index ≥30 kg m-2 based on self-reported weight and height. The association between physical inactivity and obesity was assessed with multivariable logistic regression in people with difficulties seeing and hearing, adjusting for significant covariates. RESULTS: Multivariable logistic regression analyses showed that the association between physical inactivity and obesity was stronger in those with difficulty hearing (OR 1.778, 95% CI 1.215-2.602) compared with difficulty seeing (OR 1.375, 95% CI 1.076-1.756). Gender-stratified analyses showed significant association between physical inactivity and obesity in men who reported difficulty hearing (OR 2.319, 95% CI 1.441-3.735) and difficulty seeing (OR 1.556, 95% CI 1.079-2.244), but not in women. CONCLUSIONS: A significant association between physical inactivity and obesity was observed in Spanish men with vision and hearing difficulties. Physical activity has an important role in the prevention of obesity in men with seeing and hearing difficulties. Active steps should be taken to encourage physical activity to reduce the risk of obesity in people with sensory impairments.

Seasonal Changes in 25(OH)D Concentration in Young Soccer Players-Implication for Bone Resorption Markers and Physical Performance.

Searching for potential relations between changes in 25(OH)D concentration and in physical fitness is an interesting scientific topic. Thus, the main purpose of this study was to investigate the changes in serum concentrations of 25(OH)D in young football players in conjunction with indicators determining bone resorption and physical fitness. A total of 35 young soccer players were tested during the autumn competition period. Biochemical analysis of blood, aerobic capacity, running speed and power tests (Wingate test, squat jump, counter movement jump) were carried out at the beginning and at the end of the competition period. Significant decrements in concentration of 25(OH)D from 33.9 ± 5.87 to 23.7 ± 5.58 ng/mL were noted after the analyzed competition period. There were no significant changes in aerobic capacity along the competition period. Significant improvements were observed in 10 m sprint, 30 m sprint (p < 0.001), maximal power (p = 0.011) and total work capacity (p = 0.024). We found that the effect of changes in the players' physical fitness does not occur in relation to 25 OH(D) concentration but occurs when these changes are analyzed as a function of the duration of the observation period. Changes in physical fitness of soccer players are determined by other factors then 25(OH)D concentration.

Assessment of the diet of male adolescents suffering from type 1 diabetes.

INTRODUCTION: Currently, 5-10% of diabetes patients are teenagers. During this period the influence of peers and observation of their eating habits plays a significant role. Unfortunately, they differ from the principles of proper nutrition, which according to the PTD Diabetes Poland should be introduced as an element of proper metabolic compensation. Aim of the study: To assess the condition and dietary habits of male adolescents with type 1 diabetes and to compare their eating habits to generally accepted standards. MATERIAL AND METHODS: The study participants include 20 boys, aged 14.6 ±1.58 years, with type 1 diabetes mellitus treated with a personal insulin pump who were diagnosed using ISPAD criteria. In the study anthropometric and questionnaire methods were used, as well as body composition analysis. RESULTS: In most of the examined subjects, the assessment of nutritional status indicates a proper proportion of adipose tissue (14.72 ±6.25%, 8.71 ±4.10 kg per kg) and muscle mass in the body (28.2 ±6.93 kg). Unfortunately in a significant group of adolescents, the diet is not properly balanced. Particularly the common problem is the excess of total carbohydrates, including simple sugars. CONCLUSIONS: To sum up, despite systematic education of proper nutrition on glycemic control and prevention of acute and chronic complications, the eating habits of male adolescents differ from those of proper nutrition. Additionally, it should be noted that despite the proper results of the body composition analysis, there is a problem with an erroneously balanced diet.

Evaluation of Cysteine Metabolism in the Rat Liver and Kidney Following Intravenous Cocaine Administration and Abstinence.

Many toxic effects of cocaine are attributed to reactive oxygen species (ROS) generated during its metabolism. Recently, it has been suggested that the biological action of ROS is often confused with endogenously generated reactive sulfur species (RSS). The aim of this study was to evaluate the impact of cocaine on thiols and RSS in the rat liver and kidney in the drug self-administration (SA) paradigm and the cocaine yoked delivery model (YC) followed by drug abstinence with extinction training. The level of thiols as well as RSS formed during anaerobic metabolism of cysteine and sulfate were assayed. In addition, the activity of enzymes involved in RSS formation and glutathione metabolism were determined. In the liver, following direct cocaine administration (SA and YC), the RSS levels decreased, while in the kidneys, cocaine increased the RSS contents in both groups. These changes were maintained in these tissues during drug abstinence. The level of sulfates was changed by cocaine only in the liver. In the kidney, cocaine shifted cysteine metabolism towards an anaerobic pathway. Our study demonstrates for the first time the changes in cysteine metabolism and thiol levels in the liver and kidney of rats after cocaine self-administration and abstinence.

Responses to Low- and High-Intensity Exercise in Adolescents with Type 1 Diabetes in Relation to Their Level of VO2 Max.

The purpose of this study was to investigate the influence of maximal oxygen uptake (VO2 max) on the glycemic changes during low and high intensity exercises in young type 1 diabetic patients. Twenty boys (age: 14.3 ± 1.6 years; height: 171.0 ± 11.3 cm; weight; 59.5 ± 12.8 kg) were divided into low-fit group (LFG, n = 10) and high-fit group (HFG, n = 10). According to the experimental design, participants performed three physical efforts (VO2 max test, mixed aerobic-anaerobic effort and aerobic effort) on the cycloergometer, during which real-time glycemia was measured. Mixed aerobic-anaerobic exercise demanded significantly smaller carbohydrate supplementation (0.2 ± 0.2 g/kg during exercise) than the aerobic test session (0.4 ± 0.3 g/kg during exercise). Moreover, patients with higher VO2 max had lower tendency for glycemic changes during the aerobic effort. The results of the current study suggest that young type 1 diabetic patients should perform different intensity activities using continuous glycemic monitoring system to avoid acute and chronic complications of the disease.

Comparison of physical activity levels in Spanish adults with chronic conditions before and during COVID-19 quarantine.

BACKGROUND: This is the first study analyzing levels of physical activity in a sample of quarantined adults with chronic conditions. The aim of this study was to compare moderate- and vigorous-intensity physical activity levels in Spanish adults with chronic conditions before and during coronavirus disease 2019 (COVID-19) quarantine. METHODS: A cross-sectional online survey was administered during the COVID-19 quarantine in Spain. A total of 163 participants with chronic conditions (113 females and 47 males; age range 18-64 years) completed the survey. A total of 26 chronic conditions were included. Participants self-reported average minutes/day of moderate and vigorous physical activity before and during quarantine. Differences in moderate- and vigorous-intensity physical activity levels before and during COVID-19 quarantine (overall, by gender, by age, by number of chronic conditions and by each chronic condition) were assessed by Wilcoxon-signed rank test. RESULTS: During COVID-19 quarantine, there was a significant decrease of moderate-intensity physical activity in Spanish people with chronic conditions (in both males and females, in those aged 18-24, 25-34, 35-44 and 55-64 years, in those with multimorbidity, in those with one/two chronic condition/s, and in those diagnosed with asthma/hypercholesterolaemia/chronic skin disease/haemorrhoids). Also, there was a significant decrease of vigorous-intensity physical activity in Spanish males with chronic conditions and in those with multimorbidity. CONCLUSIONS: These results should be considered to develop effective strategies of physical activity promotion targeting these specific groups when new quarantine or restriction measures are implemented, in order to avoid new significant decreases of physical activity in these vulnerable populations.

The impact of GABAB receptors and their pharmacological stimulation on cocaine reinforcement and drug-seeking behaviors in a rat model of depression.

Depression and cocaine use disorder represent frequent co-current diagnoses and the GABAB receptors are involved in both conditions. This research involved the application of the animal model of depression (bulbectomy, OBX) and cocaine use disorder (self-administration) to assess the efficiency of GABAB receptor agonists, baclofen and SKF-97541, on cocaine rewarding property and reinforcement of seeking-behaviors in rats with depressive phenotype. Additionally, we applied immunoreactive techniques to determine changes in the expression of GABAB receptor subunit 1 and 2 in rats with depression and cocaine addiction. The results obtained the study illustrate that the GABAB receptor agonists reduced the rewarding property of cocaine in both OBX and control (SHAM) rats. Both agonists significantly reduced cue- and cocaine-induced reinstatement in both groups. This is the first report demonstrating a different impact of cocaine abuse on GABAB receptor levels in depressed animals. It was documented that the expression of GABAB1 subunit in the infralimbic cortex increased during self-administration and extinction training in OBX animals. The lower level of expression for this subunit in addictive SHAM rats during self-administration, and increased in extinguished addictive OBX rats was found in the ventrolateral striatum. The expression of GABAB2 subunit changed only in the case of cocaine self-administration paradigm, as a decline of the subunit level in the nucleus accumbens and ventral hippocampus was observed only in OBX rats. The relevance of GABAB receptors in depression and addiction comorbidity is clearly implicated and can open a new era of drug discovery for individuals with dual diagnosis.

Comparison of physical activity levels in Spanish people with diabetes with and without cataracts.

BACKGROUND: The objective was to compare levels of physical activity (PA) in a large sample of Spanish people with diabetes with and without cataracts. To our knowledge, this is the first study comparing PA levels in people with diabetes with and without cataracts in a large representative sample. METHODS: Cross-sectional data from the Spanish National Health Survey 2017 were analyzed (n = 1014 people with diabetes; 43.1% females; age range 15-69 years; mean age 58.4 ± 9.2 years). International Physical Activity Questionnaire (IPAQ) short form was used to measure PA. Total MET-min week-1 of PA were calculated and participants were divided into two categories according to American Diabetes Association PA guidelines: (i) <600 MET-min week-1. (ii) At least 600 MET-min week-1. Diabetes and cataracts were self-reported in response to the questions 'Have you ever been diagnosed with diabetes/cataracts?' Participants also reported other variables including age, gender, marital status, living as a couple, education, smoking, alcohol consumption and obesity. Statistical analysis was performed with SPSS 23.0. RESULTS: The overall prevalence of cataract was 14.0% and the overall prevalence of people doing <600 MET-min week-1 of PA was 35.4%. The prevalence of cataract was significantly lower in those doing more PA (12.1% vs. 17.5%; P = 0.016). Those without cataracts were significantly more active than those with cataracts (1846.8 vs. 1289.4 MET-min week-1; P = 0.001). The adherence to American Diabetes Association PA guidelines was significantly higher in those without cataracts (66.1% vs. 55.6%; P = 0.016). CONCLUSIONS: Interventions to promote PA targeting people with both diabetes and cataracts are warranted.