Vitamin D Modulates the Response of Patient-Derived Metastatic Melanoma Cells to Anticancer Drugs.

Melanoma is considered a lethal and treatment-resistant skin cancer with a high risk of recurrence, making it a major clinical challenge. Our earlier studies documented that 1,25(OH)2D3 and its low-calcaemic analogues potentiate the effectiveness of dacarbazine and cediranib, a pan-VEGFR inhibitor. In the current study, a set of patient-derived melanoma cultures was established and characterised as a preclinical model of human melanoma. Thus, patient-derived cells were preconditioned with 1,25(OH)2D3 and treated with cediranib or vemurafenib, a BRAF inhibitor, depending on the BRAF mutation status of the patients enrolled in the study. 1,25(OH)2D3 preconditioning exacerbated the inhibition of patient-derived melanoma cell growth and motility in comparison to monotherapy with cediranib. A significant decrease in mitochondrial respiration parameters, such as non-mitochondrial oxygen consumption, basal respiration and ATP-linked respiration, was observed. It seems that 1,25(OH)2D3 preconditioning enhanced cediranib efficacy via the modulation of mitochondrial bioenergetics. Additionally, 1,25(OH)2D3 also decreased the viability and mobility of the BRAF+ patient-derived cells treated with vemurafenib. Interestingly, regardless of the strict selection, cancer-derived fibroblasts (CAFs) became the major fraction of cultured cells over time, suggesting that melanoma growth is dependent on CAFs. In conclusion, the results of our study strongly emphasise that the active form of vitamin D, 1,25(OH)2D3, might be considered as an adjuvant agent in the treatment of malignant melanoma.

Effect of a 6-Week Cycle of Nordic Walking Training on Vitamin 25(OH)D3, Calcium-Phosphate Metabolism and Muscle Damage in Multiple Myeloma Patients-Randomized Controlled Trial.

Introduction: Multiple myeloma (MM) is a hematological malignancy affecting older adults. One of the most common myeloma-defining events is the development of symptomatic lytic bone disease. The serum concentrations of calcium (Ca), inorganic phosphorus (P), and vitamin 25(OH)D3 in the serum reflect bone metabolism. An enzyme lactate dehydrogenase (LDH) is a marker of muscle damage, but its serum activity also has an important prognostic value in MM. Myoglobin (Mb) is a small protein present in muscles; its serum level increases when myocytes are damaged. Objectives: In this study, the impact of a 6-week Nordic walking (NW) exercise program on blood parameters related to calcium-phosphate metabolism and damage of skeletal muscles was assessed. Patients and methods: A total of 33 patients with MM in the remission stage, without cytostatic treatment, were allocated and randomly assigned to one of two groups: 17 in the training group (NW) and 16 in the control group (CG). All patients were supplemented per os with vitamin D3 and calcium carbonate daily and received zoledronic acid every 4 weeks (intravenous). Nordic walking training sessions took place 3 times a week for 6 weeks, 1 h each. Blood samples were drawn before and after the 6 weeks of training sessions to assess the serum concentrations of vitamin 25(OH)D3, P, Ca, Mb, and LDH. Results: Patients from the NW group showed a statistically significant decrease in mean serum myoglobin concentration (p = 0.018) and an increase in 25(OH)D3 (p < 0.001) and total Ca (p = 0.001) concentrations. There were no statistically significant changes in the results obtained in CG. Between groups, after 6 weeks, Mb serum concentration was significantly lower in NW (p = 0.041), and 25(OH)D3 was higher (p < 0.001) compared to CG. There was a correlation between the changes in myoglobin, phosphorus, 25(OH)D3, and Ca concentrations after 6 weeks. Conclusions: NW training is a safe and beneficial form of physical exercise for patients with MM without inducing muscle damage. NW performed outside improves serum vitamin 25(OH)D3 concentration.

Differences in the Pro/Antioxidative Status and Cellular Stress Response in Elderly Women after 6 Weeks of Exercise Training Supported by 1000 mg of Vitamin C Supplementation.

Vitamin C supplementation and exercise influence pro/antioxidative status and the cellular stress response. We tested the effects of exercise training for 6 weeks, supported by 1000 mg of vitamin C supplementation in elderly women. Thirty-six women were divided into two groups: a control group (CON) (n = 18, age 69.4 ± 6.4 years, 70.4 ±10.4 kg body mass) and a supplemented group (SUPP) (n = 18, aged 67.7 ± 5.6 years, body mass 71.46 ± 5.39 kg). Blood samples were taken twice (at baseline and 24 h after the whole period of training), in order to determine vitamin C concentration, the total oxidative status/capacity (TOS/TOC), total antioxidant status/capacity (TAS/TAC), and gene expression associated with cellular stress response: encoding heat shock factor (HSF1), heat shock protein 70 (HSPA1A), heat shock protein 27 (HSPB1), and tumor necrosis factor alpha (TNF-α). We observed a significant increase in TOS/TOC, TAS/TAC, and prooxidant/antioxidant balance in the SUPP group. There was a significant decrease in HSPA1A in the CON group and a different tendency in the expression of HSF1 and TNF-α between groups. In conclusion, vitamin C supplementation enhanced the pro-oxidation in elderly women with a normal plasma vitamin C concentration and influenced minor changes in training adaptation gene expression.

Effect of six weeks 1000 mg/day vitamin C supplementation and healthy training in elderly women on genes expression associated with the immune response - a randomized controlled trial.

BACKGROUND: In this study, we investigated the effects of supplementation and exercise on the expression of genes associated with inflammation like CCL2, CRP, IL1, IL6, IL10 mRNA in elderly women. METHODS: Twenty four participants divided randomly into two groups were subjected to 6 weeks of the same health training program (three times per week). SUP group (supplemented, n = 12, mean age 72.8 ± 5.26 years and mean body mass 68.1 ± 8.3 kg) received 1000 mg of Vitamin C/day during the training period, while CON group (control, n = 12, mean age 72.4 ± 5.5 years and body mass 67.7 ± 7.5 kg) received placebo. RESULTS: No significant changes in IL-1, IL-6, IL-10 and CRP mRNA were observed within and between groups. However, there was a clear tendency of a decrease in IL-6 (two-way ANOVA, significant between investigated time points) and an increase in IL-10 mRNA noted in the supplemented group. A significant decrease in CCL2 mRNA was observed only in the CON group (from 2^0.2 to 2^0.1, p = 0.01). CONCLUSIONS: It can be concluded, that 6 weeks of supplementation and exercise was too short to obtain significant changes in gene expression in leukocytes, but supplementation of 1000 mg vitamin C positively affected IL-6 and IL-10 expression - which are key changes in the adaptation to training. However, changes in body mass, IL1 and CCL2 were positive in CON group. It is possible that Vitamin C during 6 weeks of supplementation could have different effects on the expression of individual genes involved in the immune response. TRIAL REGISTRATION: Retrospectively registered.

Mitochondrial function is controlled by melatonin and its metabolites in vitro in human melanoma cells.

Melanoma is a leading cause of cancer deaths worldwide. Although immunotherapy has revolutionized the treatment for some patients, resistance towards therapy and unwanted side effects remain a problem for numerous individuals. Broad anti-cancer activities of melatonin are recognized; however, additional investigations still need to be elucidated. Herein, using various human melanoma cell models, we explore in vitro the new insights into the regulation of melanoma by melatonin and its metabolites which possess, on the other side, high safety profiles and biological meaningful. In this study, using melanotic (MNT-1) and amelanotic (A375, G361, Sk-Mel-28) melanoma cell lines, the comparative oncostatic responses, the impact on melanin content (for melanotic MNT-1 melanoma cells) as well as the mitochondrial function controlled by melatonin, its precursor (serotonin), a kynuric (N1 -acetyl-N2 -formyl-5-methoxykynuramine, AFMK) and indolic pathway (6-hydroxymelatonin, 6(OH)MEL and 5-methoxytryptamine, 5-MT) metabolites were assessed. Namely, significant disturbances were observed in bioenergetics as follows: (i) uncoupling of oxidative phosphorylation (OXPHOS), (ii) attenuation of glycolysis, (iii) dissipation of mitochondrial transmembrane potential (mtΔΨ) accompanied by (iv) massive generation of reactive oxygen species (ROS), and (v) decrease of glucose uptake. Collectively, these results together with previously published reports provide a new biological potential and make an imperative to consider using melatonin or its metabolites for complementary future treatments of melanoma-affected patients; however, these associations should be additionally investigated in clinical setting.

Vitamin D Enhances Anticancer Properties of Cediranib, a VEGFR Inhibitor, by Modulation of VEGFR2 Expression in Melanoma Cells.

Regardless of the recent groundbreaking introduction of personalized therapy, melanoma continues to be one of the most lethal skin malignancies. Still, a substantial proportion of patients either fail to respond to the therapy or will relapse over time, representing a challenging clinical problem. Recently, we have shown that vitamin D enhances the effectiveness of classical chemotherapeutics in the human malignant melanoma A375 cell line. In search for new combination strategies and adjuvant settings to improve melanoma patient outcomes in the current study, the effects of cediranib (AZD2171), an oral tyrosine kinase inhibitor of VEGFR1-3, PDGFR, and c-KIT, used in combination either with 1,25(OH)2D3 or with low-calcemic analog calcipotriol were tested on four human malignant melanoma cell lines (A375, MNT-1, RPMI-7951, and SK-MEL-28). Melanoma cells were pretreated with vitamin D and subsequently exposed to cediranib. We observed a marked decrease in melanoma cell proliferation (A375 and SK-MEL-28), G2/M cell cycle arrest, and a significant decrease in melanoma cell mobility in experimental conditions used (A375). Surprisingly, concurrently with a very desirable decrease in melanoma cell proliferation and mobility, we noticed the upregulation of VEGFR2 at both protein and mRNA levels. No effect of vitamin D was observed in MNT-1 and RPMI-7951 melanoma cells. It seems that vitamin D derivatives enhance cediranib efficacy by modulation of VEGFR2 expression in melanoma cells expressing VEGFR2. In conclusion, our experiments demonstrated that vitamin D derivatives hold promise as novel adjuvant candidates to conquer melanoma, especially in patients suffering from vitamin D deficiency. However, further extensive research is indispensable to reliably assess their potential benefits for melanoma patients.

Exercise Training and Vitamin C Supplementation Affects Ferritin mRNA in Leukocytes without Affecting Prooxidative/Antioxidative Balance in Elderly Women.

Physical training and antioxidant supplementation may influence iron metabolism through reduced oxidative stress and subsequent lowering of mRNA levels of genes that are easily induced by this stress, including those responsible for iron homeostasis. Fifteen elderly women participated in our 12-week experiment, involving six weeks of training without supplementation and six weeks of training supported by oral supplementation of 1000 mg of vitamin C daily. The participants were divided into two groups (n = 7 in group 1 and n = 8 in group 2). In group 1, we applied vitamin C supplementation in the first six weeks of training, while in group 2 during the remaining six weeks of training. In both phases, the health-related training occurred three times per week. Training accompanied by vitamin C supplementation did not affect prooxidative/antioxidative balance but significantly decreased ferritin heavy chain (FTH) and ferritin light chain (FTL) mRNA in leukocytes (for FTH mRNA from 2^64.24 to 2^11.06, p = 0.03 in group 1 and from 2^60.54 to 2^16.03, p = 0.01 in group 2, for FTL mRNA from 2^20.22 to 2^4.53, p = 0.01 in group 2). We concluded that vitamin C supplementation might have caused a decrease in gene expression of two important antioxidative genes (FTH, FTL) and had no effect on plasma prooxidative/antioxidative balance.

The influence of Finnish sauna treatments on the concentrations of nitric oxide, 3-nitrotyrosine and selected markers of oxidative status in training and non-training men.

OBJECTIVES: The aim of the study was to evaluate the effects of repeated Finnish sauna baths on the concentrations of nitric oxide metabolites (NOx) and 3-nitrotyrosine in relation to pro-oxidative and antioxidative status in young males with different physical activity levels. MATERIAL AND METHODS: The study was performed on healthy males (aged 20-25 years), representing the training (T, N = 10) and non-training groups (NT, N = 10). The protocol included a series of 10 sauna baths during 3 weeks. One bath consisted of three 15-min sessions, with 2 min recovery. Before the first and the 10th treatment, measurements of body composition, blood pressure, rectal temperature, and plasma concentrations of the total pro-oxidative and antioxidative status, 3-nitrotyrosine and NOx were performed. RESULTS: A significant increase in physiological parameters during sauna treatments, as well as a significant decrease in the total antioxidative status before the 10th bath, were observed in both groups. The series of sauna baths caused a significant increase in the total antioxidative status in the T group, and a decrease in the total oxidative status in the NT group. A significant decrease in 3-nitrotyrosine in both groups before the last treatment, and also in the T group after the last treatment, was noted. In both groups, a significant increase in NOx concentrations was observed after the first bath. CONCLUSIONS: A series of sauna baths contributes to the improvement in the prooxidative/ antioxidative balance. The increased production of nitric oxide may lead to a better vascular relaxation and blood flow. Int J Occup Med Environ Health. 2020;33(2):173-85.

[Changes in selected physiological indicators and thermal stress assessment under the influence of baths in a dry and wet sauna in young healthy women]. / Zmiany wybranych wskazników fizjologicznych oraz ocena stresu cieplnego pod wplywem kapieli w saunie suchej i mokrej u mlodych zdrowych kobiet.

BACKGROUND: There are differences between dry and wet sauna baths because of the heat load and human body's reactions. High humidity in a wet sauna makes evaporation of sweat from the skin surface more difficult. In addition, the dynamics of sweating is different in men and women. The aim of the study was to assess changes in physiological indicators and to compare the impact of dry and wet saunas on the thermal comfort feeling, which was assessed using the Bedford thermal scale, and the physiological strain index (PSI) and the cumulative heat stress index (CHSI) in young healthy women. MATERIAL AND METHODS: Ten women aged 22-24 years took part in the study. A session in each sauna lasted 60 min and consisted of 3 thermal 15-min exposures, in 5-min intervals for rest and cooling with water. The temperature in the dry sauna was 91±1.2°C and in the wet sauna 59±1.3°C, while the humidity was 18±0.7% and 60.5±0.8%, respectively. Body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), rectal temperature (Tre) and the thermal sensation (Bedford scale) were also measured. The PSI and CHSI values were both calculated. RESULTS: The average weight loss after a dry sauna bath was significantly higher than after a wet sauna bath. Significantly higher increases in Tre, as well as in HR were observed after treatment in the wet sauna, compared to the dry sauna. Both treatments resulted in an increase in SBP and a decrease in DBP. The arduousness of thermal discomfort and the levels of PSI and CHSI were skurgreater in the wet sauna bathing than in the dry sauna. CONCLUSIONS: Heat exposure in the wet sauna creates a greater burden for young women's bodies than the same dry sauna treatment, and the changes observed in the examined traits were higher than in men subjected to similar thermal loads. Med Pr. 2019;70(6):701-10.

The Impact of Vibration Therapy Interventions on Skin Condition and Skin Temperature Changes in Young Women with Lipodystrophy: A Pilot Study.

BACKGROUND: Cellulite affects 85-98% of women aged over 20 years. In a given context, mechanical vibrations have not been applied in the therapy of gynoid lipodystrophy (GL) until now. The aim of this pilot study was to assess the condition and temperature of skin affected by cellulite after vibration therapy interventions in young women with GL. METHODS: 10 healthy women (21.5 ± 1.5 years old) with stage 1 or 2 Nürnberger-Müller scale of severity of GL participated in the study. The subjects underwent 20 vibration interventions with the use of a Rehabilitation Massage Device Vitberg+. Vibration therapy was applied 5 times a week for 60 minutes during 4-week period. Before and after first and last interventions, grade of lipodystrophy was assessed and thermographic images were taken. RESULTS: Visual and palpation analysis performed before and after a series of treatments proved a total cellulite remission after the intervention among 40% of subjects (from stage 1 to stage 0). Among the remaining 60% with stage 2 of cellulite, an improvement in the skin condition was observed, and cellulite grade was determined as stage 1. The mean skin temperature in the lateral part of thigh as well as on the posterior surface of thigh and buttocks increased significantly (p<0.00001) after both the first (respectively: 4.0°C ± 0.9°C, 3.9°C ± 0.8°C) and the last vibration therapy interventions (respectively: 3.1°C ± 1.1°C, 2.8°C ± 1.1°C). After the series of interventions, a statistical significant (p=0.00705) increase in the mean skin temperature in the lateral thigh was observed-before the first treatment: 27.9°C ± 0.7°C; before twentieth treatment: 29.0°C ± 1.2°C. CONCLUSION: The series of vibration interventions contributed to the reduction of GL among the participants. The thermographic imaging analysis proved an impact of both single and serial vibration interventions.

The Possibilities of Using Chromium Salts as an Agent Supporting Treatment of Polycystic Ovary Syndrome.

The polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women in reproductive age with the so far undetermined causes of development. In the etiopathogenesis of PCOS, the role of insulin resistance is emphasised, which was an indication for the attempts at using chromium III salts (Cr) in augmenting pharmacotherapy applied in patients. The analysis of the usefulness and efficacy of this approach was the direct goal of this thesis. Animal tests confirmed the efficacy of chromium in maintaining the appropriate level of glycaemia and insulinaemia, normalisation of plasma concentrations of microelements and also a correlation between the Cr level, insulin and dehydroepiandrosterone (DHEA) was found. A decrease in the expression of 3ß-hydroxysteroid dehydrogenase and 17ß-hydroxysteroid dehydrogenase was identified in adipose tissue. Clinical studies, although sparse, show that the supplementation with chromium can improve BMI and the parameters evaluating the control of glycaemia and increase the chances for ovulation and regular menstruation. However, the small number and a variability in study protocols makes comparing them very difficult. A completely new subject that has not been yet studied is the possibility of using chromium in levelling mood disorders in patients with PCOS. Currently, there are still no sufficient proofs for introducing chromium as a standard in treating and preventing insulin resistance in patients with PCOS. However, this direction remains open, and treating insulin resistance is an important challenge in clinical practice.

Prudent-Active and Fast-Food-Sedentary Dietary-Lifestyle Patterns: The Association with Adiposity, Nutrition Knowledge and Sociodemographic Factors in Polish Teenagers-The ABC of Healthy Eating Project.

A holistic approach to understanding the relationship between diet, lifestyle and obesity is a better approach than studying single factors. This study presents the clustering of dietary and lifestyle behaviours to determine the association of these dietary-lifestyle patterns (DLPs) with adiposity, nutrition knowledge, gender and sociodemographic factors in teenagers. The research was designed as a cross-sectional study with convenience sampling. The sample consisted of 1549 Polish students aged 11⁻13 years. DLPs were identified with cluster analysis. Logistic regression modelling with adjustment for confounders was applied. Three dietary-lifestyle patterns were identified: Prudent-Active (29.3% of the sample), Fast-food-Sedentary (13.8%) and notPrudent-notFast-food-lowActive (56.9%). Adherence to Prudent-Active pattern (reference: notPrudent-notFast-food-lowActive) was 29% or 49% lower in 12-year-old or 13-year-old teenagers than in 11-year-old teenagers, respectively, and higher by 57% or 2.4 times in the middle or the upper tertile than the bottom tertile of the nutrition knowledge score. To the contrary, adherence to Fast-food-Sedentary (reference: notPrudent-notFast-food-lowActive) was lower by 41% or 58% in the middle or the upper tertile than the bottom tertile of the nutrition knowledge score, respectively. In Prudent-Active, the chance of central obesity (waist-to-height ratio ≥0.5) was lower by 47% and overweight/obesity was lower by 38% or 33% (depending on which standard was used: International Obesity Task Force, 2012: BMI (body mass index)-for-age ≥ 25 kg/m² or Polish standards, 2010: BMI-for-age ≥ 85th percentile) when compared with the notPrudent-notFast-food-lowActive pattern. In Fast-food-Sedentary, the chance of central obesity was 2.22 times higher than the Prudent-Active pattern. The study identified a set of characteristics that decreased the risk of general and central adiposity in teenagers, which includes health-promoting behaviours related to food, meal consumption and lifestyle. Avoiding high-energy dense foods is insufficient to prevent obesity, if physical activity and the consumption frequency of health-promoting foods are low and breakfast and a school meal are frequently skipped. The results highlight the importance of the nutrition knowledge of teenagers in shaping their health-promoting dietary habits and active lifestyle to decrease adiposity risk and negative aspects of lower family affluence which promotes unhealthy behaviours, both related to diet and lifestyle.

[Biological significance of chromium III for the human organism]. / Biologiczne znaczenie chromu III dla organizmu czlowieka.

Currently, chromium is probably the most controversial transition metal. In recent publications it is clearly stated that it is not an essential micronutrient and should be considered to have a pharmacological effect. Conflicting scientific reports along with a huge amount of dietary supplements, as well as dietary and sports nutrients available on the market have prompted the authors to investigate the available information on the range of possible application, efficacy and safety of products containing salts or chelates of chromium III. The authors reviewed articles in electronic databases for the years 1959-2016, and selected works describing the biochemical, physiological and toxic properties of chromium salts and chelates and the range of possible applications in medicine, dietetics and sport. A critical analysis of reports dealing with the effect of chromium on the carbohydrate and lipid metabolism, body composition, lean body mass and sports performance was carried out. The authors indicated papers analyzing the mechanism of action of chromium in the cognitive and affective disorders. Much attention has been paid to the safety use of chromium III supplements. There are still some unsolved issues. In the field of toxicology, a limited number of reports about environmental exposure to trivalent chromium in the workplace draws our attention. In the field of biochemical research, there is still a need to clarify the mechanism of psychiatric and endocrinological activity, especially in conjunction with the immune system. Med Pr 2018;69(2):211-223.

Blockade of P2X4 Receptors Inhibits Neuropathic Pain-Related Behavior by Preventing MMP-9 Activation and, Consequently, Pronociceptive Interleukin Release in a Rat Model.

Neuropathic pain is still an extremely important problem in today's medicine because opioids, which are commonly used to reduce pain, have limited efficacy in this type of pathology. Therefore, complementary therapy is needed. Our experiments were performed in rats to evaluate the contribution of the purinergic system, especially P2X4 receptor (P2X4R), in the modulation of glia activation and, consequently, the levels of nociceptive interleukins after chronic constriction injury (CCI) of the right sciatic nerve, a rat model of neuropathic pain. Moreover, we studied how intrathecal (ith.) injection of a P2X4R antagonist Tricarbonyldichlororuthenium (II) dimer (CORM-2) modulates nociceptive transmission and opioid effectiveness in the CCI model. Our results demonstrate that repeated ith. administration of CORM-2 once daily (20 µg/5 µl, 16 and 1 h before CCI and then daily) for eight consecutive days significantly reduced pain-related behavior and activation of both spinal microglia and/or astroglia induced by CCI. Moreover, even a single administration of CORM-2 on day 7 after CCI attenuated mechanical and thermal hypersensitivity as efficiently as morphine and buprenorphine. In addition, using Western blot, we have shown that repeated ith. administration of CORM-2 lowers the CCI-elevated level of MMP-9 and pronociceptive interleukins (IL-1ß, IL-18, IL-6) in the dorsal L4-L6 spinal cord and/or DRG. Furthermore, in parallel, CORM-2 upregulates spinal IL-1Ra; however, it does not influence other antinociceptive factors, IL-10 and IL-18BP. Additionally, based on our biochemical results, we hypothesize that p38MAPK, ERK1/2 and PI3K/Akt but not the NLRP3/Caspase-1 pathway are partly involved in the CORM-2 analgesic effects in rat neuropathic pain. Our data provide new evidence that P2X4R may indeed play a significant role in neuropathic pain development by modulating neuroimmune interactions in the spinal cord and DRG, suggesting that its blockade may have potential therapeutic utility.

Vitamin D derivatives enhance cytotoxic effects of H2O2 or cisplatin on human keratinocytes.

Although the skin production of vitamin D is initiated by ultraviolet radiation type B (UVB), the role vitamin D plays in antioxidative or pro-oxidative responses remains to be elucidated. We have used immortalized human HaCaT keratinocytes as a model of proliferating epidermal cells to test the influence of vitamin D on cellular response to H2O2 or the anti-cancer drug, cisplatin. Incubation of keratinocytes with 1,25(OH)2D3 or its low calcemic analogues, 20(OH)D3, 21(OH)pD or calcipotriol, sensitized cells to ROS resulting in more potent inhibition of keratinocyte proliferation by H2O2 in the presence of vitamin D compounds. These results were supported by cell cycle and apoptosis analyses, and measurement of the mitochondrial transmembrane potentials (MMP), however some unique properties of individual secosteroids were observed. Furthermore, in HaCaT keratinocytes treated with H2O2, 1,25(OH)2D3, 21(OH)pD and calcipotriol stimulated the expression of SOD1 and CAT genes, but not SOD2, indicating a possible role of mitochondria in ROS-modulated cell death. 1,25(OH)2D3 also showed a short-term, protective effect on HaCaT keratinocytes, as exemplified by the inhibition of apoptosis and the maintenance of MMP. However, with prolonged incubation with H2O2 or cisplatin, 1,25(OH)2D3 caused an acceleration in the death of the keratinocytes. Therefore, we propose that lead vitamin D derivatives can protect the epidermis against neoplastic transformation secondary to oxidative or UV-induced stress through activation of vitamin D-signaling. Furthermore, our data suggest that treatment with low calcemic vitamin D analogues or the maintenance of optimal level of vitamin D by proper supplementation, can enhance the anticancer efficacy of cisplatin.

The renaissance of vitamin D.

There is no doubt that vitamin D plays a crucial role in the maintenance of musculoskeletal system. But the function of this ancient molecule presumably ranges far beyond hormone-like regulation, as it could be generated by simple unicellular organisms. First, we are going to discuss the role of vitamin D as a global regulator of homeostasis from a historical perspective, but later we will focus on current views and its relevance to human physiology and pathology. Three milestones are defining the impact of vitamin D on science and humanity. Firstly, discovery that vitamin D is the cure for rickets, brought us supplementation programs and rapid irradiation of this devastating disease. Secondly, detail description of photoproduction of vitamin D, its subsequent metabolism and interaction with vitamin D receptor VDR, provided mechanistic background for future discoveries. Finally, recent large epidemiological studies provided indirect, but strong evidence that optimal level of vitamin D in serum has beneficial effects on our health and protects us from multiple diseases, including cancer. Furthermore, existence of alternative pathways of vitamin D metabolism and multiple intracellular targets broadens our understanding of its physiological activities and offers new and very promising tools for prophylactics and treatment of many diseases of civilization. Although vitamin D (and its derivatives) should not be regarded as a cure-all for every human disease, its beneficial effects on the human health have to be taken under consideration.

Chirp-evoked otoacoustic emissions in children.

OBJECTIVE: The purpose of the study was to investigate the properties of otoacoustic emissions (OAEs) evoked by chirp stimuli and compare them with standard click-evoked OAEs. Differences between evoked OAEs in children with and without spontaneous otoacoustic emissions (SOAEs) were also assessed. METHODS: OAEs were first recorded from 54 children (age 4-10 years) in a screening setup. In each ear five OAE measurements were made using two types of chirps (7.5 ms and 10.5 ms) at around 70 dB pSPL; clicks at 70 and 80 dB pSPL; and a standard synchronized SOAE stimulation protocol. Tympanometry was also conducted. Pass/refer criteria based on signal to noise ratios (SNRs) were applied to all OAEs. Pass/refer rates from all methods (OAEs evoked by chirps and clicks, and tympanometry) were compared. Additionally, half-octave-band values of OAE SNRs and response levels were used to assess statistical differences. RESULTS: Chirp-evoked OAEs generated a similar number of passes to click-evoked OAEs when the same level of stimulus was used. When using lower stimulus levels, both chirp- and click-evoked OAEs diagnosed nearly all ears that failed tympanometry. The response levels and SNRs of OAEs evoked by clicks and chirps were very similar. The highest response levels were in the 1.4 kHz half-octave band. The SNRs for ears with SOAEs were highest at 1.4 kHz, whereas they were at 4 kHz for ears without SOAEs. Both response levels and SNRs were higher by about 5 dB for ears with SOAEs than ears without SOAEs. Also all ears with SOAEs generated a pass result in screening, while ears without SOAEs gave a pass less frequently (at least 30% fewer cases). CONCLUSIONS: The results suggest that performance of chirp-evoked OAEs for screening purposes is similar to click-evoked OAEs when the same stimulus level is applied. OAEs evoked with lower stimulus levels (70 vs. 80 dB pSPL) are more sensitive to middle ear pathology. The presence of SOAEs significantly influences the pass rates of OAEs evoked by chirps and clicks.

[Evaluation of the possibilities to increase the content of conjugated linoleic acid (CLA) in meat and meat product]. / Ocena mozliwosci zwiekszenia zawartosci sprzezonych dienów kwasu linolowego (CLA) w miesie i przetworach miesnych.

The paper characterizes pro-health properties of conjugated linoleic acid (CLA) and assesses the possibility of increasing their content in pork and pork meat products. Studies conducted on animals indicate antitumor, antiatherosclerotic and antiinflammatory effect ofCLA, also find impact on reducing body fat and increasing muscle growth. However, the number of observations concerning human populations is insufficient to fully evaluate the relationship between CLA intake and reducing the risk of lifestyle diseases. Therefore, it is necessary to conduct further research. Literature data indicate that the use in pigs feed suplementation with CLA preparations, can increase the content of these compounds in the meat and also show, that isomer cis-9, trans-11 is accumulated at significantly higher level. However, these changes were accompanied by increased the share of saturated fatty acids at the expense of monounsaturated which is unfavorable for human health. A better way to increase the CLA content in pork meat appears to be the addition of CLA preparation during the production process, because it does not affect the level of saturated fats. Pork and pork meat products enriched in CLA are characterized by low susceptibility to oxidation, which may result from the coupling of double bonds, antioxidantive properties of conjugated linoleic acid and the increased content of saturated fatty acids. The issue of beneficial effects on human health of pork and pork products with a higher content of CLA, requires further studies conducted on humans. Only then these products can be classified as a functional foods.

Results of partial deafness cochlear implantation using various electrode designs.

Nineteen adults and 9 children who received a unilateral cochlear implant between 2002 and 2007 were included in the study. All subjects were preoperatively diagnosed with significant residual hearing in low frequencies, termed as 'partial deafness', and were implanted according to a 6-step round window surgical technique for partial deafness cochlear implantation. Hearing was preserved to a great extent in the partial deafness cochlear implantation (PDCI) group. After a short period following activation of the cochlear implant, highly significant improvement in the recognition of monosyllabic words was observed. With a developed round window surgical procedure and limited electrode insertion, hearing can be preserved in the majority of patients with partial deafness. PDCI is a feasible means of treating individuals who have good low-frequency hearing but severe to profound hearing loss in the mid to high frequencies.

Zinc-induced adaptive changes in NMDA/glutamatergic and serotonergic receptors.

Preclinical data indicate the involvement of glutamatergic and serotonergic pathways in the antidepressant activity of zinc. The present study investigated alterations in N-methyl-D-aspartate (NMDA)/glutamatergic and serotonergic receptors (using radioligand binding) induced by chronic treatment (14-day) with zinc hydroaspartate (65 mg/kg). Moreover, the mRNA and protein levels of brain-derived neurotrophic factor (BDNF) were also assessed. Chronic zinc administration reduced the affinity of glycine to glycine/NMDA receptors in the rat frontal cortex and increased the density of 5-HT(1A) and 5-HT(2A) serotonin receptors in the hippocampus and frontal cortex, respectively. These receptor alterations may be in part due to increased BDNF mRNA and protein levels in the rat frontal cortex. These results indicate that chronic zinc treatment alters glutamatergic and serotonergic systems, which is a hallmark of clinically effective antidepressants.