LUNGBANK: a novel biorepository strategy tailored for comprehensive multiomics analysis and P-medicine applications in lung cancer.

Background/aim: LUNGBANK was established as part of Project LUNGMARK, pioneering a biorepository dedicated exclusively to lung cancer research. It employs cutting-edge technologies to streamline the handling of biospecimens, ensuring the acquisition of high-quality samples. This infrastructure is fortified with robust data management capabilities, enabling seamless integration of diverse datasets. LUNGBANK functions not merely as a repository but as a sophisticated platform crucial for advancing lung cancer research, poised to facilitate significant discoveries. Materials and methods: LUNGBANK was meticulously designed to optimize every stage of biospecimen handling, from collection and storage to processing. Rigorous standard operating procedures and stringent quality control measures guarantee the integrity of collected biospecimens. Advanced data management protocols facilitate the efficient integration and analysis of various datasets, enhancing the depth and breadth of research possibilities in lung cancer. Results: LUNGBANK has amassed a comprehensive collection of biospecimens essential for unraveling the intricate molecular mechanisms of lung cancer. The integration of state-of-the-art technologies ensures the acquisition of top-tier data, fostering breakthroughs in translational and histological research. Moreover, the establishment of patient-derived systems by LUNGBANK underscores its pivotal role in personalized medicine approaches. Conclusion: The establishment of LUNGBANK marks a significant milestone in addressing the critical challenges of lung cancer research. By providing researchers with high-quality biospecimens and advanced research tools, LUNGBANK not only supports Project LUNGMARK's objectives but also contributes extensively to the broader landscape of personalized medicine. It promises to enhance our understanding of lung cancer initiation, progression, and therapeutic interventions tailored to individual patient needs, thereby advancing the field towards more effective diagnostic and therapeutic strategies.

Nutrition Messaging by Healthcare Students: A Mixed-Methods Study Exploring Social Media Usage and Digital Competence.

AIM: The COVID-19 pandemic leads to a significant digital transformation in higher education and healthcare practices. This study aimed to investigate the level of digital competence, views and experiences, social media usage, and perceived barriers to digital communication among healthcare students. METHOD: Employing a mixed-methods approach, quantitative data were gathered through an online survey, while qualitative insights were gleaned from semi-structured questionnaire responses obtained during focus group discussions. A total of 143 nursing and midwifery students from Turkey, along with 54 dietetics students from various European countries, participated in the study. RESULTS: A significant proportion of nursing (43.5%) and midwifery (55.2%) students advocated for integrating digital technology training into university curricula. Instagram has emerged as the predominant platform for sharing healthcare/nutrition information among students. However, concerns have been raised regarding the prevalence of "before/after" posts on social media promoting weight loss, which were identified as low-quality content by participants. CONCLUSIONS: These findings underscore the importance of integrating digital technologies and social media into healthcare, nutrition education, and practice. Additionally, there is a pressing need to establish professional and ethical standards for digital nutritional communication. By addressing these challenges, educators can better equip healthcare students to navigate the complexities of modern healthcare practices and enhance patient-care outcomes.

Trans isomeric fatty acids in human milk and their role in infant health and development.

It is well known that long chain polyunsaturated fatty acids (LCPUFAs) play an important role in neurodevelopment in the perinatal life. The most important source of these fatty acids is the diet, however, they can also be formed in the human body from their shorter chain precursors, the essential fatty acids. Since the WHO recommends exclusive breastfeeding for the first six months after birth, the exclusive source of these fatty acids for breastfed infants is human milk, which can be influenced by the mother's diet. Unsaturated fatty acids can have either cis or trans configuration double bond in their chain with distinct physiological effects. Cis isomeric unsaturated fatty acids have several beneficial effects, while trans isomers are mostly detrimental, because of their similar structure to saturated fatty acids. Trans fatty acids (TFAs) can be further subdivided into industrial (iTFA) and ruminant-derived trans fatty acids (rTFA). However, the physiological effects of these two TFA subgroups may differ. In adults, dietary intake of iTFA has been linked to atherosclerosis, insulin resistance, obesity, chronic inflammation, and increased development of certain cancers, among other diseases. However, iTFAs can have a negative impact on health not only in adulthood but in childhood too. Results from previous studies have shown that iTFAs have a significant negative effect on LCPUFA levels in the blood of newborns and infants. In addition, iTFAs can affect the growth and development of infants, and animal studies suggest that they might even have lasting negative effects later in life. Since the only source of TFAs in the human body is the diet, the TFA content of breast milk may determine the TFA supply of breastfed infants and thus affect the levels of LCPUFAs important for neurodevelopment and the health of infants. In this review, we aim to provide an overview of the TFA content in human milk available in the literature and their potential effects on infant health and development.

The role of cell cycle progression for the apoptosis of cancer cells induced by palladium(II)-saccharinate complexes of terpyridine.

OBJECTIVES: Palladium complexes are potent and less toxic molecules in comparison to other metal based agents. Here, we characterized two palladium(II) saccharinate complexes with terpyridine for their cell cycle specificity. MATERIALS AND METHODS: Cells were arrested at G1, G1/S boundary or mitosis using mimosine, double-Thymidine block, aphidicolin, nocodazole or colcemid, and evaluated based on morphology and flow cytometry. Synchronized cells were treated with the Pd(II) complexes, and viability was measured via MTT assay. RESULTS: While treatment of arrested cells with the Pd(II) complexes resulted in no significant change in cell death in HCT-116 and MDA-MB-231 cells, HeLa cells were more sensitive in S/G1. The main form of cell death was found to be apoptosis. CONCLUSIONS: Pd(II) complexes appear to be cell-cycle non-specific, while cell line dependent differences may be observed. Cells die through apoptosis regardless of the cell cycle stage, which makes these complexes more promising as anti-cancer agents.

Executive dysfunction and cognitive subgroups in a large sample of euthymic patients with bipolar disorder.

Bipolar disorder (BP), at the group level, is associated with significant but modest cognitive deficits, including executive dysfunction. Among executive functions, response inhibition deficits have been suggested to be particularly relevant to BP. However, BP is associated with significant heterogeneity in neurocognitive performance and level of functioning. Very few studies have investigated neurocognitive subgroups in BP with data-driven methods rather than arbitrarily defined criteria. Other than having relatively small sample sizes, previous studies have not taken into consideration the neurocognitive variability in healthy subjects. Five-hundred-fifty-six euthymic patients with BP and 416 healthy controls were assessed using a battery of cognitive tests and clinical measures. Neurocognitive subgroups were investigated using latent class analysis, based on executive functions. Four neurocognitive subgroups, including a good performance cluster, two moderately low-performance groups, which differ in response inhibition and reasoning abilities, and a severe impairment cluster were found. In comparison to healthy controls, BP patients were overrepresented in severe impairment cluster (27% vs 5.3%) and underrepresented in good performance cluster. BP patients with lower educational attainment and older age were significantly more likely to be members of cognitively impaired subgroups. Antipsychotic use was less common in good performance cluster. These results suggest that there is a considerable overlap of cognitive functions between BP and healthy controls. Neurocognitive differences between BP and healthy controls are driven by a subgroup of patients who have severe and global, rather than selective, cognitive deficits.

Evaluation of apoptotic molecular pathways for smooth muscle cells isolated from thoracic aortic aneurysms in response to oxidized sterols.

Oxysterols, oxygenated derivatives of cholesterol, are found abundantly in the plasma and atherosclerotic plaques, a common risk factor for thoracic aortic aneurysms (TAAs). Among the oxysterols, namely 7-ketocholesterol (7-KC) and 25-hydroxycholesterol (25-OHC), lead both to induction of reactive oxygen species (ROS) in cells and to apoptosis in smooth muscle cells (SMCs) probably due to increased oxidative stress. Since loss of SMCs through apoptosis is a major event in TAA formation, it is important to understand the molecular pathways of apoptosis in response to ROS in TAAs. Very little is known about the effect of oxysterols on TAA SMCs. Therefore, we investigated molecular pathways participating in the oxysterol induced cell death of TAAs. Our results showed that TAA SMCs died mainly as a result of apoptosis as suggested by cellular shrinkage, blebbing, DNA condensation/fragmentation in response to oxysterol treatment. There was no significant difference in oxysterol induced cell death between TAA and control SMCs. Addition of antioxidant molecules prevented cell death, hence ROS appears to be involved in the apoptosis of these cells. While oxysterol treatment increased caspase 3 activity, cell death was not rescued in its absence. Efficient silencing of other targets including apoptotic proteins (p53, Bax), and survival proteins (Akt1, Akt2) showed that apoptosis can occur through p53, and Bax independent pathways. Silencing Akt1 or Akt2 did not lead to further cell death. These results indicate that oxysterols can induce several cell death pathways in TAA SMCs.

Biochemical and proteomic analysis of a potential anticancer agent: Palladium(II) Saccharinate complex of terpyridine acting through double strand break formation.

Metal based chemotherapeutic drugs are widely used as an effective method to defeat various cancers. In this study, the mechanism of action of a novel therapeutic agent, [Pd(sac)(terpy)](sac)·4H2O (sac = saccharinate, and terpy = 2,2':6',2″-terpyridine) was studied. To better understand the proteomic changes in response to this agent, we performed nano LC-MS/MS analyses in human breast cancer cells (MDA-MB-231). Thirty proteins were identified to be differentially expressed more than 40% after drug treatment. Many cellular pathways were affected, including proteins involved in DNA repair, apoptosis, energy metabolism, protein folding, cytoskeleton, pre-mRNA maturation, or protein translation. The changes in protein expression were further verified for XRCC5, which plays a role in double strand break (DSB) repair, and ubiquitin, which is involved in protein degradation and apoptosis. The elevated XRCC5 levels were suggestive of increased DSBs. The presence of DSBs was confirmed by smearing of plasmid DNA in vitro and induction of γH2AX foci in vivo. There was also increased intracellular reactive oxygen species (ROS) formation, as detected by 2',7'-dichlorofluorescein diacetate (DCFDA) staining. Scavenging ROS by N-acetylcysteine rescued cell death in response to Pd(II) treatment, potentially explaining how the Pd(II) complex damaged the DNA. The details of this analysis and the significance will be discussed during the scope of this work.

Obestatin improves ischemia/reperfusion-induced renal injury in rats via its antioxidant and anti-apoptotic effects: role of the nitric oxide.

Obestatin was shown to have anti-inflammatory effects in several inflammatory models. To elucidate the potential renoprotective effects of obestatin, renal I/R injury was induced in male Sprague Dawley rats by placing a clamp across left renal artery for 60min following a right nephrectomy. Clamp was released and the rats were injected with either saline or obestatin (10, 30, 100µg/kg). In some experiments, obestatin (10µg/kg) was administered with L-NAME (10mg/kg) or L-Nil (0.36mg/kg). Following a 24-h reperfusion, the rats were decapitated to measure serum creatinine and nitrite/nitrate levels, renal malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activity and to assess cortical necrosis and apoptosis scores. Obestatin treatment reduced I/R-induced increase in creatinine levels, renal MPO activity and renal MDA levels, while renal GSH levels were significantly increased by obestatin. Histological analysis revealed that severe I/R injury and high apoptosis score in the kidney samples of saline-treated rats were significantly reduced and the cortical/medullary injury was ameliorated by obestatin. Expression of eNOS, which was increased by I/R injury, was further increased by obestatin, while serum NO levels were significantly decreased. iNOS inhibitor L-Nil reduced oxidative renal damage and improved the functional and histopathological parameters. I/R-induced elevation in eNOS expression, which was further increased by obestatin, was depressed by L-NAME and L-Nil treatments. The present data demonstrate that obestatin ameliorates renal I/R-injury by its possible anti-oxidative, anti-inflammatory and anti-apoptotic properties, which appear to involve the suppression of neutrophil accumulation and modulation of NO metabolism.

Metacognitive beliefs in unipolar and bipolar depression: a comparative study.

AIMS: The purpose of this study was to perform a comparative investigation of metacognitive beliefs regarding pathological worry in patients with unipolar and bipolar depressive disorder. METHODS: Those subjects with acute depressive episodes among patients diagnosed with major depressive disorder (unipolar) or bipolar disorder on the basis of DSM-IV diagnostic criteria (unipolar n = 51, bipolar n = 45), and healthy controls (n = 60), were included in the study. Participants were administered the Meta-Cognitions Questionnaire (MCQ-30) in order to determine metacognitive beliefs. The relationship between metacognitive beliefs and anxiety severity, depression severity and self-esteem in the unipolar and bipolar patients groups was then examined. RESULTS: Scores for negative beliefs about worry concerning uncontrollability and danger and for beliefs about the need to control thoughts were higher in both the unipolar and bipolar depression groups than in the healthy controls (P < 0.05). Lack of cognitive confidence scores were higher in the bipolar group than in the healthy controls (P < 0.05). Metacognitive beliefs (to a greater extent in parameters in the bipolar group) were correlated with anxiety level, depression level and self-esteem in both patient groups. CONCLUSION: In addition to metacognitive beliefs known to be associated with ruminations in unipolar and bipolar depression, metacognitive beliefs can also be seen in association with worry. Worry-associated metacognitive beliefs should be the subject of focus in the identification of metacognitive beliefs in depression patients and in metacognitive therapy in these patients.

Evaluation of the molecular mechanisms of a palladium(II) saccharinate complex with terpyridine as an anticancer agent.

Metal-based compounds represent promising anticancer therapeutic agents. In this study, the mechanism of action of a novel metal-based drug, a palladium(II) (Pd) complex ([PdCl(terpy)](sac)·2H2O, terpy=2,2':6',2''-terpyridine and sac=saccharinate), was elucidated. The tested compound induced cytotoxicity in nine different human cancer cell lines that originated from various organs, suggesting a broad spectrum of activity. The IC50 values were significantly higher for noncancerous cells when compared with cancer cells. We found that cells treated with the Pd(II) complex exhibited increased caspase 3/7 activities and condensed/fragmented nuclei, as demonstrated by nuclear staining and DNA laddering. Morphological features, such as cellular shrinkage and blebbing, were also observed, indicating that apoptosis was the primary mechanism of cell death. Pd(II) treatment induced DNA double-stranded breaks both in vitro and in vivo, potentially accounting for the source of stress in these cells. Although caspase 3/7 activities were elevated after Pd(II) treatment, silencing or using inhibitors of caspase 3 did not block apoptosis. Other molecules that could potentially play a role in Pd(II)-induced apoptosis, such as p53 and Bax, were also tested using silencing technology. However, none of these proteins were essential for cell death, indicating either that these molecules do not participate in Pd(II)-induced apoptosis or that other pathways were activated in their absence. Hence, this new molecule might represent a promising anticancer agent that exhibits cytotoxicity in p53-mutant, Bax-mutant, and/or caspase 3-mutant cancer cells.

A novel method to differentiate bovine and porcine gelatins in food products: nanoUPLC-ESI-Q-TOF-MS(E) based data independent acquisition technique to detect marker peptides in gelatin.

We presented a novel nanoUPLC-MS(E) workflow method that has potential to identify origin of gelatin in some dairy products; yoghurt, cheese and ice cream. In this study, the method was performed in two steps. In the first step, gelatin was extracted from these products before the MS-sample preparation. In the second step, tryptic gelatin peptides were separated and analyzed with ultra-performance liquid chromatography and electrospray ionization quadrupole time-of-flight mass spectrometry (nanoUPLC-ESI-q-TOF-MS(E)). The novelty of this setup was that it functioned in a data independent acquisition mode and that alternate low and elevated collision energy was applied to acquire precursor and product ion information. This enabled accurate mass acquisition on the peptide level to identify the gelatin peptides. The marker peptides specific for porcine and bovine could be successfully detected in the gelatin added to the dairy products analyzed, revealing that the detection of marker peptides in the digested gelatin samples using nanoUPLC-ESI-q-TOF-MS(E) could be an effective method to differentiate porcine and bovine gelatin in the dairy products.

Internalized stigma and intimate relations in bipolar and schizophrenic patients: a comparative study.

OBJECTIVE: The aim of this study was to determine characteristics of internalized stigma and intimate relations in bipolar and schizophrenia patients and to compare characteristics of intimate relations in bipolar and schizophrenia patients with or without internalized stigma. METHOD: A total of 228 volunteers were included, 119 patients with bipolar disorder and 109 with schizophrenia. Schizophrenic and bipolar disorder patients were compared in terms of internalized stigma and intimate relations characteristics. Bipolar and schizophrenia patients with and without internalized stigma were compared in terms of characteristics of intimate relations. RESULTS: Internalized stigma was determined in one in three schizophrenia and one in five bipolar patients. Stigma resistance and relational esteem in intimate relations scores were higher in bipolar patients. Relational anxiety/fear of relationship, relational monitoring and external relational control scores were higher in schizophrenia patients with internalized stigma compared to those without, while their relational satisfaction, relational esteem and relational assertiveness scores were lower. Relational anxiety/fear of relationship and relational monitoring scores were higher in bipolar patients with internalized stigma compared to those without, while their relational satisfaction scores were lower. CONCLUSION: Internalized stigma in schizophrenia patients is a well-known subject that has been investigated previously. The results of our study are significant in terms of showing that internalized stigma is also frequent in bipolar disorder patients, and not solely in schizophrenia patients. Stigma resistance is higher in bipolar disorder patients. Internalized stigma is correlated with intimate relations in both bipolar and schizophrenia patients.

Combination of fenretinide and indole-3-carbinol results in synergistic cytotoxic activity inducing apoptosis against human breast cancer cells in vitro.

The outcome in patients with breast cancer is not satisfactory to date, although new chemotherapy regimens have been introduced in clinics. Therefore, novel approaches are required for better management of patients with breast cancer. In this study, we tested the cytotoxic activity of a new combination of fenretinide, a synthetic retinoid, with indole-3-carbinol, a natural product present in vegetables such as broccoli and cabbage, against MCF-7 (estrogen receptor-positive) and MDA-MB-231 (estrogen receptor-negative) cell lines. It has been found that the combination resulted in more powerful cytotoxic activity, by induction of apoptosis, compared with that when they were used singly. In conclusion, this novel combination warrants in-vivo experiments to elucidate its possible use in the treatment of breast cancer.

Smooth muscle cells isolated from thoracic aortic aneurysms exhibit increased genomic damage, but similar tendency for apoptosis.

Aortic aneurysms (AA) are characterized by structural deterioration leading to progressive dilation. During the development of AA, two key structural changes are pronounced, one being degradation of extracellular matrix and the other loss of smooth muscle cells (SMCs) through apoptosis. Reactive oxygen species (ROS) are produced above physiological levels in dilated (aneurismal) part of the aorta compared to the nondilated part and they are known to be associated with both the extracellular matrix degradation and the loss of SMCs. In this study, we hypothesized that aneurismal SMCs are more prone to apoptosis and that at least some cells undergo apoptosis due to elevated ROS in the aortic wall. To test this hypothesis, we first isolated SMCs from thoracic aneurismal tissue and compared their apoptotic tendency with normal SMCs in response to H(2)O(2), oxidized sterol, or UV treatment. Exposed cells exhibited morphological changes characteristic of apoptosis, such as cell shrinkage, membrane blebbing, chromatin condensation, and DNA fragmentation. Terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) further confirmed the fragmentation of nuclear DNA in these cells. Vascular SMCs were analyzed for their micronuclei (MN) and binucleate (BN) frequency as indicators of genomic abnormality. These data were then compared to patient parameters, including age, gender, hypertension, or aortic diameter for existing correlations. While the tendency for apoptosis was not significantly different compared to normal cells, both the %MN and %BN were higher in aneurismal SMCs. The data suggest that there is increased DNA damage in TAA samples, which might play a pivotal role in disease development.

Temperament and character traits in patients with bipolar disorder and associations with attempted suicide.

OBJECTIVE: This study was intended to investigate temperament and character traits in bipolar disorder patients with or without a history of attempted suicide. METHODS: One hundred nineteen patients diagnosed with euthymic bipolar disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and with no accompanying Axis I and II comorbidity, and 103 healthy controls were included. Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I and II disorders were used to exclude Axis I and II comorbidity. Temperament and character traits of bipolar patients with a history attempted suicide (25.2%, n = 30) or without (74.8%, n = 89) and of the healthy volunteers were determined using the Temperament and Character Inventory. The association between current suicide ideation and temperament and character traits was also examined. RESULTS: Bipolar patients with or without a history of attempted suicide had higher harm avoidance (HA) scores compared with the healthy controls. Persistence scores of bipolar patients with no history of attempted suicide were lower than those of the healthy controls. Self-directedness (SD) scores of the bipolar patients with a history of attempted suicide were lower than those of patients with no such history. Self-transcendence scores of bipolar patients with no history of attempted suicide were lower than those of both the healthy controls and of those patients with a history of attempted suicide. A positive correlation was determined between current suicidal ideation scale scores and HA, and a negative correlation between SD and cooperativeness was determined. CONCLUSIONS: High harm avoidance may be a temperament trait specific to bipolar disorder patients. However, it may not be correlated with attempted suicide in such patients. These may have low persistence, high SD and low self-transcendence temperament and character traits that protect against attempted suicide. Harm avoidance, SD, and cooperativeness may be correlated with current suicidal ideation.

Identification of novel neutralizing single-chain antibodies against vascular endothelial growth factor receptor 2.

Human vascular endothelial growth factor (VEGF) and its receptor (VEGFR-2/kinase domain receptor [KDR]) play a crucial role in angiogenesis, which makes the VEGFR-2 signaling pathway a major target for therapeutic applications. In this study, a single-chain antibody phage display library was constructed from spleen cells of mice immunized with recombinant human soluble extracellular VEGFR-2/KDR consisting of all seven extracellular domains (sKDR D1-7) to obtain antibodies that block VEGF binding to VEGFR-2. Two specific single-chain antibodies (KDR1.3 and KDR2.6) that recognized human VEGFR-2 were selected; diversity analysis of the clones was performed by BstNI fingerprinting and nucleotide sequencing. The single-chain variable fragments (scFvs) were expressed in soluble form and specificity of interactions between affinity purified scFvs and VEGFR-2 was confirmed by ELISA. Binding of the recombinant antibodies for VEGFR-2 receptors was investigated by surface plasmon resonance spectroscopy. In vitro cell culture assays showed that KDR1.3 and KDR2.6 scFvs significantly suppressed the mitogenic response of human umbilical vein endothelial cells to recombinant human VEGF(165) in a dose-dependent manner, and reduced VEGF-dependent cell proliferation by 60% and 40%, respectively. In vivo analysis of these recombinant antibodies in a rat cornea angiogenesis model revealed that both antibodies suppressed the development of new corneal vessels (p < 0.05). Overall, in vitro and in vivo results disclose strong interactions of KDR1.3 and KDR2.6 scFvs with VEGFR-2. These findings indicate that KDR1.3 and KDR2.6 scFvs are promising antiangiogenic therapeutic agents.

The involvement of nitric oxide and endothelin-1 in exercise-induced bronchospasm in young soccer players.

OBJECTIVES: To investigate the levels of nitric oxide (NO) and endothelin-1 (ET-1) in soccer players with exercise-induced bronchospasm (EIB), to test whether these endogenous vasoactive molecules are involved in the development of EIB, and to examine the possible participation of reactive oxygen metabolites in these alterations. DESIGN: Observational study. SETTING: Football club. PARTICIPANTS: Forty-three soccer players (N = 43) aged 16 to 22 years performed maximal exercise test on a treadmill by using Bruce protocol. INTERVENTIONS: Respiratory function tests were evaluated before and after exercise tests. Participants were grouped as control (n = 35) or EIB (n = 8) groups according to the respiratory function test results. MAIN OUTCOME MEASURES: Endothelin-1 (ET-1), nitric oxide (NO), carbonyl, malondialdehyde, and glutathione levels were determined from the blood samples taken before and after exercise tests. RESULTS: In the control group, significant decreases in plasma ET-1 and serum NO levels were determined after exercise. On the other hand, plasma malondialdehyde and carbonyl levels were significantly decreased, whereas glutathione levels were significantly increased after exercise. In the EIB group, blood levels of NO, ET-1, carbonyl, and malondialdehyde after exercise were found to be significantly increased compared with pre-exercise levels. CONCLUSIONS: These findings demonstrate that in young soccer players, EIB is associated with elevated serum NO and plasma ET-1 levels. Moreover, significant increases in lipid peroxidation and protein oxidation and decreases in antioxidant sulfhydryl (RSH) content indicate a significant compromise in the blood antioxidant status and the presence of systemic oxidative stress in young athletes with EIB.

Diet-supported aerobic exercise reduces blood endothelin-1 and nitric oxide levels in individuals with impaired glucose tolerance.

BACKGROUND: Impaired glucose tolerance (IGT) forms an intermediate stage in the natural history of diabetes mellitus. Insulin-resistant states might be associated with dysfunction of the vascular endothelium. OBJECTIVES: To determine the effects of chronic exercise and a low-calorie diet on plasma nitric oxide (NO) and endothelin-1 (ET-1) levels in patients with IGT and to elucidate the relationship between the oxidant stress markers and NO/ET-1 levels of blood before and after exercise. METHODS: Patients with IGT (n = 14) participated in a regular exercise program and exercised for 40 minutes each day, 3 days a week for 12 weeks. Physiological, anthropometric, and biochemical measurements were performed before, during the 6th week, and at the end of the program. RESULTS: There was a significant reduction in body mass index, body fat content, systolic and diastolic blood pressures, as well as NO and ET-1 concentrations after 12 weeks of exercise and diet program. Exercise training significantly elevated subjects' maximum oxygen consumption, whereas the resting metabolic rates of the patients did not change. The formation of thiobarbituric acid reactive substances were significantly reduced, whereas sulfhydryl groups were significantly increased on the 6th week (P < .05) and at the end of program (P < .01). CONCLUSION: Our results demonstrate that exercise, along with low-calorie diet, induced reductions in the plasma of both ET-1 and NO. Beneficial effects were observed on anthropometric measurements and plasma oxidant stress markers, indicating weight loss associated with exercise training and calorie restriction may effectively improve endothelial dysfunction in patients with IGT.