Metabolic control level and glucose variability in adolescents with type 1 diabetes during low and high-intensity exercise.

OBJECTIVE: The main purpose of this study was to characterize the determinants of metabolic changes in young type 1 diabetes (T1DM) and to determine glycemic variability during low and high-intensity exercise. PATIENTS AND METHODS: 20 young male T1DM patients were divided into two subgroups characterized by levels of glycated hemoglobin (HbA1c): HbA1c<7.3% (better HbA1c subgroup, n=10) and with levels HbA1c>7.3% (worse HbA1c subgroup, n=10). All participants performed a maximal oxygen uptake test and two efforts of various intensities (45 minutes of aerobic exercise and 30 minutes of mixed aerobic-anaerobic intensity exercise). Continuous glucose monitors (CGM) were used to control the glucose concentration. RESULTS: Changes in biomarkers describing the metabolic response were similar in both groups. A comparison of applied efforts exhibited that maximal capacity effort resulted in the highest values of blood glucose (BG) at the end (150.9-160.6 mg/dl) and 1 hour after the exercise (140.2-161.3 mg/dl). BG concentration before, during, 1 hour, and 24 hours after each exercise was insignificantly higher in the worse Hb1Ac group. CONCLUSIONS: HbA1c levels are insufficient to confirm whether the applied effort is performed in acceptable glycemic values. The CGM monitors allow for precise control of BG variations and accurate planning of physical activity by adjusting the insulin and carbohydrate consumption dose.

Performance improvement in sport through vitamin D - a narrative review.

OBJECTIVE: It is well known that vitamin D deficiency can lead to various health problems. However, it is not common knowledge among athletes and doctors that vitamin D deficiency is prevalent in sports. This deficiency can severely impact performance, while vitamin D supplementation can alleviate this effect and potentially improve performance. MATERIALS AND METHODS: This narrative review aims to compile the current state of knowledge about the importance of vitamin D in increasing performance for active people. To this end, we searched the 'Scopus' and 'PubMed' databases for the terms 'vitamin D - athlete - performance' with an end date of 30 June 2022. RESULTS: Study results indicated that the therapeutic impact of vitamin D on aerobic capacity, recovery, strength and sprint performance remains controversial. CONCLUSIONS: Based on the previous findings on recovery, strength and performance, 4,000-5,000 IU of vitamin D per day may be a safe dose that can improve athletic performance.

Analysis of the PPARD Gene Expression Level Changes in Football Players in Response to the Training Cycle.

The PPARD gene codes protein that belongs to the peroxisome proliferator-activated receptor (PPAR) family engaged in a variety of biological processes, including lipid metabolism in muscle cells. In this study, we assess the relationship between PPARD gene expression lipid metabolism parameters and the variation of the PPARD gene expression before (T1) and after 12 hours of training (T2) sessions in a group of football players. Peripheral blood lymphocytes were obtained from 22 football players (17.5±0.7 years, 178±0.7 cm, 68.05±9.18 kg). The PPARD gene expression, analyzed by quantitative polymerase chain reaction (qPCR), was significantly higher after T2 (p = 0.0006). Moreover, at the end of the training cycle, there was a significant decrease in relative fat tissue (FAT) (%) (p = 0.01) and absolute FAT (kg) (p = 0.01). A negative correlation was observed between absolute FAT (kg) and PPARD gene expression level in T2 (p = 0.03). The levels of cholesterol and triglyceride (TG) fractions were not significantly different (p >0.05) before and after training. No significant relationship between PPARD expression and cholesterol or TG levels was found. We found that physical training affects PPARD expression. Moreover, the negative correlation between PPARD expression and absolute FAT (kg) level may be indicative of the contribution of PPARD in metabolic adaptation to increased lipid uptake that can be used to control the body composition of athletes.

In Vitro and In Vivo (Rabbit, Guinea Pig, Mouse) Properties of a Novel Resorbable Polymer and Allogenic Bone Composite for Guided Bone Regeneration and Orthopedic Implants.

INTRODUCTION: Currently, there is no bone fixation material that could be fully replaced by the competent recipient bone. The creeping substitution of the bone graft by the recipient bone is the result of its unique potential related to the presence of bone morphogenetic proteins (BMPs). However, the size of the human bone limits the use of allogenic implants for surgical (orthopedic) fixation. The aim of this project was to develop a novel composite material for guided bone regeneration, consisting of human bone powder obtained from a tissue bank and a resorbable polymer (13 wt% of bone powder in a medical poly-l-lactide polymer). Such a biomaterial could possess osteoinductive properties and be used to manufacture bone fixation implants of different shapes and sizes. MATERIALS AND METHODS: The samples were obtained by tape casting and foils pressing, and subsequently radiation sterilized with a dose of 35 kGy. Two cell lines-normal mouse embryo fibroblasts (Balb 3T3/c) and human fetal osteoblasts (hFOB 1.19)-were cultured with the extracts of the biomaterials (MTT assay) or in indirect contact with the evaluated biomaterials (agar diffusion method). In addition, cell viability was evaluated after 5 days of incubation with biomaterial using ThinCert tissue culture inserts. Then, the following in vivo examinations were conducted: acute systemic toxicity, skin irritation and sensitization, and local effects after implantation. RESULTS: The evaluated composite material showed a high degree of cytocompatibility and biocompatibility according to the International Standards. CONCLUSIONS: The preclinical evaluation we performed on the new, polylactide-based allogenic biomaterial opens up possibilities to patent pending and advanced in vivo testing.

Changes in the acid-base balance and lactate concentration in the blood in amateur ultramarathon runners during a 100-km run.

The aim of this study was to analyse the acid-base balance and partial pressure of blood gases of participants during a 100-km run. Fourteen experienced amateur ultramarathon runners (age: 43.36±11.83 years; height: 175.29±6.98 cm; weight: 72.12±7.36 kg) completed the 100-km run. Blood samples were taken before the run; after 25, 50, 75, and 100 km; and 12 and 24 hours after the run. There were significant differences (p<0.05) between the mean values registered for acid-alkaline balance, buffering alkalies, and current bicarbonate in each segment of the run, especially during the third, fourth, and fifth segments of the run (i.e., between 50 and 100 km), and there were only significant differences associated with buffering alkalies and current bicarbonate during the recovery. However, all the changes were within the physiological norm. A significant decrease in the compressibility of oxygen was observed after 100 km (from 92.80±15.67 to 88.36±13.71 mmHg) and continued during the recovery to 75.06±8.60 mmHg 12 h after the run. Also there was a decrease in saturation to a mean value of 93.78±3.10 at 12 h after the run. Generally the amateurs runners are able to adjust their running speed so as not to provoke a significant acid-base imbalance or lactate acid accumulation.

Effects of 6-week specific low-intensity training on selected aerobic capacity parameters and HSPA1A, HSPB1, and LDHb gene expression in high-level rowers.

The aim of this study was to demonstrate the effects of 6-week low-intensity training on changes in indicators of aerobic capacity and on HSPA1A, HSPB1, and LDHb expression in white blood cells in high level rowers. We hypothesized that the type of training would have an impact not only on the adaptation of athletes to the aerobic nature of the exercises, but also on the expression of genes, designated during exercises "until refusal". Nine Polish lightweight male rowers (21.8 ± 3.77 years of age, 74.2 ± 1.7 6 kg, 184.8 ± 4.58 cm) of high level participated in the experiment. To determine the anaerobic threshold (AnT) and peak oxygen uptake (VO2max) at the beginning and end of the 6-week training period, the subjects performed the test "till exhaustion", with increasing load. Directly before and after the test, blood samples were collected from the ulnar vein for isolation of RNA. Consecutively, reverse transcription and real time polymerase chain reaction amplification was performed. A significant influence of applied training on physiological parameters such as VO2max (P = 0.0001), AnT (W/AT) (P = 0.0007), and maximal acid lactate concentration (P = 0.018) as well as on HSPA1A expression (P = 0.0129) in rowers were detected. The 6-week low-intensity aerobic training significantly affected the physiological parameters and HSPA1A expression in the rowers. Therefore, we suggest that the response of leukocytes by activating HSPA1A was dependent on the type of training. The 6-week period proved sufficiently long to of adapting leukocytes in athletes to high intensity exercises.

THE GSTP1 c.313A>G POLYMORPHISM MODULATES THE CARDIORESPIRATORY RESPONSE TO AEROBIC TRAINING.

The GSTP1 c.313A>G polymorphism is a candidate to explain some of the individual differences in cardiorespiratory fitness phenotypes' responses to aerobic exercise training. We aim to explore the association between the GSTP1 c.313A>G polymorphism and the response to low-high impact aerobic exercise training. Sixty-six Polish Caucasian women were genotyped for the GSTP1 c.313A>G polymorphism; 62 of them completed 12-week aerobic (50-75% HRmax) exercise training and were measured for selected somatic features (body mass and BMI) and cardiorespiratory fitness indices - maximal oxygen uptake (VO2max, maximum heart rate (HRmax), maximum ventilation (VEmax) and anaerobic threshold (AT) - before and after the training period. Two-factor analysis of variance revealed a main training effect for body mass reduction (p=0.007) and BMI reduction (p=0.013), improvements of absolute and relative VO2max (both p<0.001), and increased VEmax (p=0.005), but not for changes in fat-free mass (FFM) (p=0.162). However, a significant training x GSTP1 c.313A>G interaction was found only for FFM (p=0.042), absolute and relative VO2max (p=0.029 and p=0.026), and VEmax (p=0.005). As the result of training, significantly greater improvements in VO2max, VEmax and FFM were gained by the GG+GA group compared to the AA genotype group. The results support the hypothesis that heterogeneity in individual response to training stimuli is at least in part determined by genetics, and GSTP1 c.313A>G may be considered as one (of what appear to be many) target polymorphisms to influence these changes.

SOD2 gene polymorphism and muscle damage markers in elite athletes.

Exercise-induced oxidative stress is a state that primarily occurs in athletes involved in high-intensity sports when pro-oxidants overwhelm the antioxidant defense system to oxidize proteins, lipids, and nucleic acids. During exercise, oxidative stress is linked to muscle metabolism and muscle damage, because exercise increases free radical production. The T allele of the Ala16Val (rs4880 C/T) polymorphism in the mitochondrial superoxide dismutase 2 (SOD2) gene has been reported to reduce SOD2 efficiency against oxidative stress. In the present study we tested the hypothesis that the SOD2 TT genotype would be underrepresented in elite athletes involved in high-intensity sports and associated with increased values of muscle and liver damage biomarkers. The study involved 2664 Caucasian (2262 Russian and 402 Polish) athletes. SOD2 genotype and allele frequencies were compared to 917 controls. Muscle and liver damage markers [creatine kinase (CK), creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP)] were examined in serum from 1444 Russian athletes. The frequency of the SOD2 TT genotype (18.6%) was significantly lower in power/strength athletes (n = 524) compared to controls (25.0%, p = 0.0076) or athletes involved in low-intensity sports (n = 180; 33.9%, p < 0.0001). Furthermore, the SOD2 T allele was significantly associated with increased activity of CK (females: p = 0.0144) and creatinine level (females: p = 0.0276; males: p = 0.0135) in athletes. Our data show that the SOD2 TT genotype might be unfavorable for high-intensity athletic events.

The +1245g/t polymorphisms in the collagen type I alpha 1 (col1a1) gene in polish skiers with anterior cruciate ligament injury.

OBJECTIVES: The aim of this study was to examine the association of +1245G/T polymorphisms in the COL1A1 gene with ACL ruptures in Polish male recreational skiers in a case-control study. METHODS: A total of 138 male recreational skiers with surgically diagnosed primary ACL ruptures, all of whom qualified for ligament reconstruction, were recruited for this study. The control group comprised 183 apparently healthy male skiers with a comparable level of exposure to ACL injury, none of whom had any self-reported history of ligament or tendon injury. DNA samples extracted from the oral epithelial cells were genotyped for the +1245G/T polymorphisms using real-time PCR method. RESULTS: Genotype distributions among cases and controls conformed to Hardy-Weinberg equilibrium (p = 0.2469 and p = 0.33, respectively). There was a significant difference in the genotype distribution between skiers and controls (p = 0.045, Fisher's exact test). There was no statistical difference in allele distribution: OR 1.43 (0.91-2.25), p = 0.101 (two-sided Fisher's exact test). CONCLUSIONS: The risk of ACL ruptures was around 1.43 times lower in carriers of a minor allele G as compared to carriers of the allele T.

Antiangiogenic effect of sulindac sulfide could be secondary to induction of apoptosis and cell cycle arrest.

BACKGROUND: The development of colon cancer is probably angiogenesis-dependent. Recently, sulindac sulfide was shown to possess anti-angiogenic activity. In the present work, the question of whether this activity reflects a specific interaction with angiogenesis or is secondary to the effect of sulindac sulfide on the survival of endothelial cells was addressed. MATERIALS AND METHODS: Endothelial and normal mouse fibroblast cell lines were incubated with non-steroidal anti-inflammatory drugs (NSAIDs), arachidonic acid (AA) and prostaglandin E2 (PGE2). Cell viability (survival), PGE2 synthesis, cell cycle and apoptosis were measured. Western blotting and semi-quantitative RT-PCR multiplex methods verified the changes in the levels of pro-apoptotic proteins and their expressions, respectively. RESULTS: Sulindac sulfide and celecoxib inhibited the survival of endothelial cells, whereas other NSAIDs were ineffective. In contrast to celecoxib, sulindac sulfide did not affect the survival of normal fibroblast cells. Both agents inhibited the production of PGE2 from AA and arrested the cell cycle in the S-phase. Moreover, sulindac sulfide activated caspases 3 and 8, decreased the levels of Bax and Bid proteins, caused cleavage of PARP and increased the expressions of the bax and caspase 3 genes. CONCLUSION: The results suggest that the anti-angiogenic activity of sulindac sulfide is secondary to the inhibition of endothelial cell survival resulting from cell cycle arrest and apoptosis.

Pharmacokinetics of selol, a new agent containing selenium, in rats.

The pharmacokinetic properties of selol, a new organoselenium compound, were evaluated in rats. Each animal was given a single oral or subcutaneous dose of selol 12 mg/kg. The selenium concentration was determined in whole blood and tissues by non flame carbon furnace atomic-absorption spectrometry. The pharmacokinetic parameters Cmax and tmax differed statistically between oral (p.o.) and subcutaneous (s.c.) treatment. The selenium average peak concentrations in the blood were 494 +/- 8 ng/ml after oral and 322 +/- 5 ng/ml after subcutaneous administration. They were reached after 1.9 +/- 0.1 h and 2.4 +/- 0.1 h, respectively. For the AUC0 mean values of 1373 +/- 56 ng.h/ml (p.o.) and 1273 +/- 137 ng.h/ml (s.c.) were found. The mean residence time (MRT) was significantly longer after subcutaneous administration. Selenium distributes quickly to the main organs with prevalence to the adrenal gland. Moreover, its concentrations in the examined organ were evidently higher after subcutaneous treatment as compared to the oral route. Our data suggest that Selol may be used as a possible source of selenium for the treatment of selenium-deficient patients, particularly via the subcutaneous route.

Activation of GABA-A receptor by hypotensive drugs.

Chronic antihypertensive treatment with clonidine and beta-adrenoceptor blockers leads to a significant increase in GABA-A receptor number in the hypothalamus, the pons-medulla and the striatum. The enhancement of receptor number after two beta-blockers was associated with the decrease of Kd factor in the pons-medulla and the striatum. There was no change in receptor affinity after clonidine. We conclude that neurotransmission via GABA-A receptors is important for the hypotensive effects of clonidine and some beta-adrenoceptor blockers.

Clonidine hypotension in spontaneously hypertensive rats (SHR) depends on the functional state of GABAergic and glutamatergic systems.

The effect of gamma-aminobutyric acid (GABA)A receptors and of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor blockade on clonidine hypotension was studied. The experiments were performed on spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. We found that the blockade of GABAA receptors line significantly (P < 0.01) reduced hypotensive responses to clonidine. Similarly, the NMDA receptor antagonist dizocilpine (MK-801) completely abolished the blood pressure lowering effect of clonidine. Our findings support the conclusion that clonidine hypotension is closely related to the functional state of both inhibitory GABAergic and excitatory glutamatergic systems.

Toxicity studies of a new selenium compound, Selol, in rats.

Selol is a new organoselenium compound synthesized in the Department of Drug Analysis, Warsaw. The general acute and cumulative toxicities of Selol were tested in rats. The compound did not display any toxic effects after parenteral administration up to 500 mg/kg-1 s.c. and 100 mg/kg-1 i.p. However, given orally it exhibited high toxicity. LD50 value after a single oral administration amounted to 100 mg/kg-1 and after administration in an increasing-dose schedule to 80 mg/kg-1. On the basis of these results the authors conclude that Selol may be converted to a more toxic product during digestion. Therefore, Selol as a source of selenium is safer given by the parenteral route.

On the role of NMDA receptors in blood pressure regulation in spontaneously hypertensive rats (SHR).

In the present study the binding of [(3)H]MK-801 to glutamatergic receptors of the NMDA type was compared in spontaneously hypertensive (SHR) and normotensive (WKY) rats in various brain structures (including nucleus tractus solitarii) by quantitative receptor autoradiography. Additionally, blood pressure changes after treatment with the NMDA antagonist MK-801 were studied in both strains. There were no differences between SHR and WKY rats either in the level of [(3)H]MK-801 binding or in the hypertensive reaction to MK-801.

Antihypertensive treatment with beta blockers and gabaergic transmission in rat brain.

The effects of chronic oral administration of propanolol and metoprolol on blood pressure and GABAergic function were investigated in spontaneously hypertensive rats (SHR) and compared with the effect of dihydralazine. Under the experiment conditions employed all drugs reduced significantly (p < 0.01) arterial pressure. The beta blockers elevated GABA turnover in the hypothalamus and the pons-medulla. Dihydralazine, however had not such an effect. Our result suggest that the antihypertensive action of beta blockers may be related in part to the enhanced cerebral GABAergic transmission.

Enhancement of GABAergic system activity by metoprolol in spontaneously hypertensive rats.

The relevance of the GABAergic system for the antihypertensive action of metoprolol in spontaneously hypertensive rats was studied by comparing the effect of metoprolol with the effect of dihydralazine. Chronic oral treatment with metoprolol produced the maximum effect after 49 days (-delta 34 mm Hg). This effect persisted on the same level for up to 55 days. The measurements of gamma-aminobutyric acid (GABA) synthesis and specific [3H]GABA binding were performed in the hypothalamus, the pons-medulla, the hippocampus and the striatum. Significant stimulation of GABA synthesis and turnover appeared in the hypothalamus and the pons medulla. In contrast, chronic administration of dihydralazine had no influence on GABA synthesis rate. It was also shown that metoprolol elevated significantly (P < 0.01) specific [3H]GABA binding in the hypothalamus and the pons-medulla. In the striatum this effect of metoprolol was less pronounced. Binding constant analysis revealed changes in both the receptor density and affinity. Our results suggest that the hypotensive response to chronic treatment with metoprolol might be attributed to an enhancement of GABAergic system activity.

Intracellular accumulation of cytosine arabinoside in murine normal and neoplastic lymphocytes following their exposure to sodium 2-mercaptoethanesulphonate.

The effect of mesna on intracellular accumulation of cytosine arabinoside (Ara-C) in murine normal and neoplastic lymphocytes was studied. Simultaneous exposure of cells to mesna at concentrations ranging from 0.25 to 1.0 mM and 3H-Ara-C (40.0 nM) resulted in a strong inhibition of Ara-C uptake in normal lymphocytes. Under the same experimental conditions, mesna did not affect the Ara-C uptake in neoplastic cells (cultured L5178Y mouse leukaemia cells and neoplastically transformed thymus cells). It was found that the inhibitory effect of mesna was not cell cycle-dependent, since mesna reduced the Ara-C uptake in both normal quiescent and PHA-stimulated cells. We therefore concluded that mesna may selectively reduce Ara-C uptake by normal cells in vitro.

Pharmacodynamic interaction of clonidine and muscimol in hypertension.

The effect of the GABA agonist muscimol on the hypotensive action of clonidine in SHR was investigated. Muscimol administered before clonidine significantly (p < 0.01) intensified clonidine-induced reduction of blood pressure. This effect was achieved at muscimol doses which themselves had no influence on blood pressure. Muscimol injected after clonidine was ineffective. Our data suggest that the muscimol-clonidine interaction occurs at the level of GABAergic neurotransmission since both agents have been proved to activate the function of GABAergic neurons.

Acute systemic toxicity and antihypertensive activity of a novel todralazine analog in rats.

Acute intravenous toxicity and antihypertensive activity of KB1, a novel todralazine analog was investigated and compared with the effects of todralazine (Td) in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. LD50 values were 72 mg.kg-1 for KB1, and 255 mg.kg-1 for Td in WKY and 43 mg.kg-1 or KB1 in SHR. Therefore, the toxicity of KB1 was higher than that of Td and it increased in SHR. The antihypertensive activity of KB1 (ED20% 9.8 mg.kg-1) in WKY was about 9 times less potent in comparison with Td (ED20% 1.1 mg.kg-1). Blood pressure reducing activity of KB1 augmented apparently in SHR (ED20% 2.5 mg.kg-1) whereas Td had not such an effect (ED20% 1.0). Thus, the influence of Td on blood pressure was similar in normotensive and hypertensive animals. Our results indicate that KB1 is capable of reducing blood pressure preferentially in hypertension.