Internet-based health communication opportunities (blogs, podcasts, video channels) and the social media / Internetalapú egészségkommunikációs lehetoségek (blogok, podcastok, videócsatornák) és a közösségi média.

Összefoglaló. Az elmúlt években mind laikus, mind szakmai oldalról az internet vált az elso számú egészségügyi információforrássá, amit a COVID-19-pandémia tovább fokozott. Az online térben számos, különbözo jellegu platform áll rendelkezésre egészségkommunikációs célokra, melyek markánsan különböznek egymástól az átadható információ mennyiségében és minoségében, a létrehozásukhoz szükséges anyagi vagy idobeli ráfordításban, továbbá az ott létrehozott tartalom fogyasztási lehetoségeiben. Összefoglaló közleményünkben rendszerezve mutatjuk be a szöveg-, a hang-, illetve a videóalapú online egészségügyi edukációs formák elonyeit és hátrányait. Külön foglalkozunk a közösségi média (social media) egészségügyi vonatkozásaival, a benne rejlo lehetoségekkel, kiemelve a pandémia kapcsán felmerült problémákat. Az egyes platformok egészségüggyel kapcsolatos történelmének feldolgozása mellett gyakorlati oldalról mutatjuk be azok hasznosíthatóságát, elosegítve ezzel az online térbe terelt kollégák munkáját. Orv Hetil. 2022; 163(4): 132-139. Summary. In recent years, the internet has become the leading source of health-related information for both professionals and laymen, and this process has been further speeded up by the Covid-19 pandemic. There are many different platforms available for health communication purposes online, that vary greatly in the quantity and quality of transferable information; the time or financial input, which are necessary to create them; and the possibilities of the utilization of the created content. In our review, we present systematically the advantages and disadvantages of the text-, audio-, and video-based online health-related education platforms. We specify the health-related aspects of social media and its potential usability, focusing on the problems allied to the pandemic. We present the practical use of the different platforms from a healthcare perspective through the review of their respective histories, thus providing guidance to the colleagues working online. Orv Hetil. 2022; 163(4): 132-139.

Mal de débarquement syndrome ­ "sickness of disembarkment" / [Mal de débarquement szindróma - "partraszállási betegség"]

Mal de débarquement syndrome is an uncommon vestibular disorder characterized by a constant sensation of swaying or motion after one disembarks from a vehicle such as a ship or plane, however, spontaneous onset also appears. These symptoms temporarily subside when the patient is subjected again to passive motion like driving a car. Chronic fatigue, anxiety, and depression are frequently associated with primary symptoms. The diagnosis is challenging, and often made by the patients themselves. The underlying pathophysiology and definitive therapy are unknown. Exposure to optokinetic stimulations and transcranial magnetic stimulations open therapeutic perspectives. We report a case series of 5 patients who presented with constant rocking, bobbing sensation that had been ongoing for several months. We found normal inner-ear function, non-related abnormalities and normal brain imaging. By presenting our patients' histories, we discuss the different diagnostic issues that help to diagnose this condition. We aimed to report the most recent findings on aetiology and treatment methods and to share our experiences with different therapeutic attempts. Mal de débarquement syndrome is a diagnosis of exclusion and often unrecognized. A thorough clinical history, negative or non-specific clinical findings with a high degree of suspicion are needed for recognizing this disorder. Increasing awareness can lead to early diagnosis and prevent multiple physician visits and unnecessary diagnostic testing. Frequent diagnostic failure has a negative impact on the quality of life, associated with anxiety and depression. Orv Hetil. 2020; 161(20): 846-851.

[Patients' preferences for health-related use of Internet]. / Betegpreferenciák az egészségügyi célú internethasználatban.

INTRODUCTION: More sophisticated implementation of the Internet in healthcare improves medical services innumerably. To better understand the patients' preferences for health-related use of Internet is warranted. AIM: Our aim was to determine the patients' health-related Internet use. METHOD: Patients attending our private clinic between October 2016 and April 2017 were surveyed. RESULTS: 208 questionnaires have been evaluated. Most patients use Internet daily, primarily on mobiles. The majority have already searched for health-related information online, 19% do regularly. 53% are satisfied with online contents and open to websites recommended by physicians. 32% of patients have already communicated with doctors online and 93% are satisfied doing so. 8% of patients use health-related smartphone applications regularly, 6% use other Internet-based health-monitoring devices. 60% of patients have already chosen a physician based on web information, while 17% do regularly. 82% of respondents have not yet shared health-related information on the Internet. CONCLUSIONS: The Internet is widely used by patients seeking information about their health, yet they are dissatisfied with the quality. Many patients are open to recommendations offered by physicians regarding sources of online information. Online communication between physician and patient might increase patient satisfaction. There is no breakthrough in the use of health-related websites, mobile apps or devices in Hungary. The demand for such service could be considered moderate. Additionally, online patient forums are not specifically popular. The medical society in Hungary should accept that physician selection by patients depends more increasingly upon information made available online. Orv Hetil. 2018; 159(51): 2175-2182.

Morbidity and mortality trends in very-very low birth weight premature infants in light of recent changes in obstetric care.

OBJECTIVE: In this study, we describe trends in morbidity and mortality of preterm infants with less than 500mg birth weight in the changing landscape of obstetric and neonatal care. STUDY DESIGN: During a ten year study period between 2006 and 2016 we assessed outcome data for all neonates with less than 500mg birth weight born at our Neonatal Intensive Care Unit. We divided study subjects into two groups based on whether their birth date fell in the first half (2006-2010; n=39) versus the second half (2011-2015; n=27) of the study period comparing clinical outcomes in the two groups. We also assessed several clinical parameters for association with postnatal survival by comparing relative frequencies for each clinical parameter among surviving infants versus mortality cases. RESULTS: Survival rate for preterm neonates with less than 500mg birth weight born between 2006 and 2010 was 30.8%. This survival rate rose to 70.4% in the second half of the study period between 2011 and 2015 (p<0.05). Among surviving babies premature birth was found to be predominantly associated with maternal hypertension or intrauterine growth restriction while in those who died premature birth due to premature rupture of membranes and spontaneous preterm labor were significantly more common. All surviving infants with less than 500mg birth weight were born via cesarean section whereas among those who died cesarean section had been performed in only 80% and vaginal delivery in 20% representing a significant difference between the groups (p<0.05). The majority (90.3%) of surviving infants with less than 500mg birth weight had received surfactant therapy while the proportion of neonates receiving surfactant therapy among mortality cases was significantly lower (65.2%; p<0.05). DISCUSSION: Our findings suggest that among premature neonates with less than 500mg birth weight preterm delivery due to premature rupture of membranes and intrauterine infections represents the worse mortality risk. Steroid prophylaxis and measures to prevent and treat intrauterine infections with appropriate use of antibiotics can markedly improve survival in these cases. In premature neonates with less than 500mg birth weight survival is more favorable after cesarean section compared to vaginal delivery.

Severe neck infections that require wide external drainage: clinical analysis of 17 consecutive cases.

Infections in the neck layers and spaces are potentially life-threatening diseases causing further complications, like mediastinitis, airway obstruction, or sepsis. Despite of the need for a conservative approach, they still regularly require surgical intervention. Records of 17 patients with severe neck infections that were treated by wide external incision and open wound management were retrospectively analyzed. The aim of the study was to clinically characterize these most serious neck infections. The most common presenting symptoms were neck pain and tense neck mass (94-94%) regularly with fever (65%), always accompanied by a marked elevation of C reactive protein level (average 192 uG/l). These findings were constant and very similar among both the deep neck infection and necrotizing fasciitis cases. More than half of the patients (53%) had at least one systemic co-morbidity. The parapharyngeal space was most commonly affected (83%), but extended disease involving more than two major neck regions was found in 13 cases (76%). Dental (29%) was the most common primary infection, followed by peritonsillar abscess (23%), Microbiological results showed a wide variety of corresponding bacteria. Mediastinitis was developed in three cases (18%), and airway obstruction requiring tracheostomy in two cases (12%). All the patients survived. Severe neck infections are a heterogenous group of diseases regarding to the primary site of infection, microbiology, localisation and host reaction. However, rapidly developed, painful, tense neck mass with a highly elevated CRP level should always alert for an extended or phlegmonous process in the layers or spaces of the neck.

Homocysteine metabolism in peripheral blood mononuclear cells: evidence for cystathionine beta-synthase activity in resting state.

Activated peripheral blood mononuclear cells (PBMC) release homocysteine and possess cystathionine ß-synthase (CBS) activity; however, it was thought that there is no CBS in resting state. Previously, we found that nickel decreased intracellular homocysteine concentration in un-stimulated (e.g. resting) PBMC, suggesting that resting PBMC might also have active homocysteine metabolism. Here, we demonstrated that un-stimulated PBMC synthesize (incorporate L-[methyl-14C]methionine to DNA, lipids and proteins), release (increase extracellular homocysteine), and metabolize homocysteine. Intracellular homocysteine concentration varied with incubation time, depending on extracellular concentrations of methionine, homocysteine, and glutathione. Methionine synthase activity was constant and independent of thiol concentrations. In Western blot, CBS protein was clearly identified in freshly isolated PBMC. CBS protein level and activity increased with incubation time, upon stimulation, and similar to intracellular homocysteine, depending on intra- and extracellular homocysteine and glutathione concentrations. According to our knowledge, this is the first evidence that certifies homocysteine metabolism and regulatory role of CBS activity to keep balanced intracellular homocysteine level in resting PBMC. Homocysteine, released by PBMC, in turn can modulate its functions contributing to the development of hyperhomocysteinemia-induced diseases.

Increased levels of platelet activation markers are positively associated with carotid wall thickness and other atherosclerotic risk factors in obese patients.

The role of platelets in the development of atherosclerosis and obesity-related prothrombotic state is still under investigation. In this cross-sectional cohort study, we measured the levels of different platelet activation markers and evaluated their relationship with carotid intima-media thickness (IMT) along with other atherosclerotic risk factors in obese patients with or without atherosclerotic co-morbidities. We enrolled 154 obese patients, including 98 with either hypertension, type 2 diabetes mellitus or dyslipidaemia, 56 without these co-morbidities and 62 age- and sex-matched healthy controls. Platelet P-selectin expression and the number of platelet-derived microparticles (PMPs) were measured by flow cytometry; soluble P-selectin levels were analysed by ELISA and Thr715Pro P-selectin polymorphism was determined by PCR-RFLP. Carotid IMT was examined by ultrasonography. The levels of platelet activation parameters were significantly elevated in all obese subjects with increased carotid IMT compared to healthy controls. There was no effect of Thr715Pro genotype on soluble P-selectin levels in obese individuals contrary to normal subjects. Significant and positive association was revealed between carotid IMT and platelet P-selectin (p<0.0001), soluble P-selectin (p=0.039) and PMP (p=0.0001) levels. After adjusting for multiple variables, independent association was found between soluble P-selectin and fibrinogen (p=0.007), PMP levels and body mass index (p<0.0001) as well as platelet P-selectin and carotid IMT (p=0.012) plus plasminogen activator inhibitor-1 (p=0.009). In conclusion, P-selectin and PMP levels showed positive associations with abnormal carotid IMT and other risk factors in obesity suggesting a critical role of enhanced platelet reactivity in atherosclerotic wall alteration.

Hydrogen sulfide inhibits the calcification and osteoblastic differentiation of vascular smooth muscle cells.

Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) is involved in the pathogenesis of vascular calcification. Hydrogen sulfide (H(2)S) is a gas endogenously produced by cystathionine γ-lyase in VSMC. Here we determined whether H(2)S plays a role in phosphate-induced osteoblastic transformation and mineralization of VSMC. Hydrogen sulfide was found to inhibit calcium deposition in the extracellular matrix and to suppress the induction of the genes involved in osteoblastic transformation of VSMC: alkaline phosphatase, osteocalcin, and Cbfa1. Moreover, phosphate uptake and phosphate-triggered upregulation of the sodium-dependent phosphate cotransporter (Pit-1) were also prevented by H(2)S. Reduction of endogenous production of H(2)S by inhibition of cystathionine γ-lyase activity resulted in increased osteoblastic transformation and mineralization. Low plasma levels of H(2)S, associated with decreased cystathionine γ-lyase enzyme activity, were found in patients with chronic kidney disease receiving hemodialysis. Thus, H(2)S is a potent inhibitor of phosphate-induced calcification and osteoblastic differentiation of VSMC. This mechanism might contribute to accelerated vascular calcification in chronic kidney disease.

Mixtures of Uncaria and Tabebuia extracts are potentially chemopreventive in CBA/Ca mice: a long-term experiment.

A long-term experimental animal model was developed by our research group for the evaluation of potential chemopreventive effects. The inhibitory effects of agents on carcinogen (7,12-dimethylbenz[a]anthracene (DMBA) induced molecular epidemiological biomarkers, in this case the expression of key onco/suppressor genes were investigated. The expression pattern of c-myc, Ha-ras, Bcl-2, K-ras protooncogene and p53 tumour suppressor gene were studied to elucidate early carcinogenic and potential chemopreventive effects. The consumption of so-called Claw of Dragon tea (CoD™ tea) containing the bark of Uncaria guianensis, Cat's Claw (Uncaria sp. U. tomentosa) and Palmer trumpet-tree (Tabebuia sp. T. avellanedae) was able to decrease the DMBA-induced onco/suppressor gene overexpression in a short-term animal experiment. In a following study CBA/Ca mice were treated with 20 mg/kg bw DMBA intraperitoneally (i.p.) and the expression patterns of onco/suppressor genes were examined at several time intervals. According to the examined gene expression patterns in this long-term experiment the chemopreventive effect of CoD™ tea consumption could be confirmed.

Red cells, hemoglobin, heme, iron, and atherogenesis.

OBJECTIVE: We investigated whether red cell infiltration of atheromatous lesions promotes the later stages of atherosclerosis. METHODS AND RESULTS: We find that oxidation of ferro (FeII) hemoglobin in ruptured advanced lesions occurs generating ferri (FeIII) hemoglobin and via more extensive oxidation ferrylhemoglobin (FeIII/FeIV=O). The protein oxidation marker dityrosine accumulates in complicated lesions, accompanied by the formation of cross-linked hemoglobin, a hallmark of ferrylhemoglobin. Exposure of normal red cells to lipids derived from atheromatous lesions causes hemolysis and oxidation of liberated hemoglobin. In the interactions between hemoglobin and atheroma lipids, hemoglobin and heme promote further lipid oxidation and subsequently endothelial reactions such as upregulation of heme oxygenase-1 and cytotoxicity to endothelium. Oxidative scission of heme leads to release of iron and a feed-forward process of iron-driven plaque lipid oxidation. The inhibition of heme release from globin by haptoglobin and sequestration of heme by hemopexin suppress hemoglobin-mediated oxidation of lipids of atheromatous lesions and attenuate endothelial cytotoxicity. CONCLUSIONS: The interior of advanced atheromatous lesions is a prooxidant environment in which erythrocytes lyse, hemoglobin is oxidized to ferri- and ferrylhemoglobin, and released heme and iron promote further oxidation of lipids. These events amplify the endothelial cell cytotoxicity of plaque components.

Associations of adiponectin with paraoxonase 1 and sE-selectin in hemodialyzed patients.

BACKGROUND/AIMS: In hemodialyzed (HD) patients, adiponectin and sE-selectin levels are elevated, while antioxidant paraoxonase 1 activity (PON1) is decreased. We determined if the hyperadiponectinemia in HD patients has a protective effect on the decrease in PON1 and elevation in sE-selectin in kidney failure. METHODS AND DESIGN: Predialysis serum adiponectin, PON1 and sE-selectin as well as other metabolic variables were measured in 70 HD patients. RESULTS: Adiponectin had (1) no association with PON1 or sE-selectin, (2) a positive association with dialysis efficiency and HDL-C, and (3) an inverse association with BMI, waist circumference, HOMA IR, triglyceride, hsCRP, fibrinogen, and albumin. Moreover, albumin, BMI, and HOMA-IR were independent negative predictors of adiponectin. CONCLUSIONS: In kidney failure, in contrast to normal renal function, higher adiponectin levels had no correlation with PON1 activity or the sE-selectin level. However, adiponectin has an association with dialysis efficiency and, similar to individuals with preserved kidney function, traits of metabolic syndrome. In addition to BMI and HOMA-IR, the serum albumin concentration is also one of the independent negative predictors of the serum adiponectin level. Collectively, these findings may add details to the understanding of the role that adiponectin plays in chronic renal disease related to 'reverse epidemiology'.

Association between XRCC1 polymorphisms and head and neck cancer in a Hungarian population.

BACKGROUND: Head and neck cancer is a significant current health problem in Hungary because the mortality of this cancer has increased by 387% in the last thirty-two years. Because of the important role of the XRCC1 gene in DNA repair, we wanted to test the effects of the Arg194Trp and Arg399Gln polymorphisms of XRCC1 on the clinical outcome of head and neck cancer. PATIENTS AND METHODS: A polymerase chain reaction-restriction fragment lenght polmorphism (PCR-RFLP) method was used. A total of 108 samples were taken from intraoperatively removed formalin-fixed, and paraffin-embedded blocks of tissue. An age- and sex-matched cancer-free control group was used to compare the frequency of polymorph variants. RESULTS: No significant difference was found between patients and controls in repect of the investigated polymorphisms. A significant difference was found between the patients with different XRCC1 194 polymorph status in clinical stage SIII. The survival proportion of patients with the Arg194Arg genotype was significantly lower than of those with the Arg194Trp genotype. CONCLUSION: The complex analysis of these factors may provide the basis for personal risk assessment and an opportunity for individualised therapy.

Early modification of c-myc, Ha-ras and p53 expressions by chemical carcinogens (DMBA, MNU).

7,12-Dimethylbenz[a]anthracene (DMBA) and N-methyl-N-nitrosourea (MNU) are important environmental carcinogens. Their different biological effects were examined in CBA/Ca H-2(K) haplotype inbred mice on the gene expression of c-myc, Ha-ras and p53 through a 24 hour period. Elevated expression of c-myc and Ha-ras genes was found in the spleen, lung, thymus and lymph nodes 6 and 12 hours after DMBA treatment and in the lung and thymus 3 hours after MNU treatment. In the liver, DMBA induced strong onco/suppressor gene expression as early as 6 hours after the treatment, but MNU increased the p53 gene expression 12 hours after the treatment. The gene expression patterns reflected the different mechanism of the direct acting MNU and metabolically activated DMBA. This phenomenon provides evidence as to the usefulness of detection of onco/supressor key gene expression as early molecular epidemiological biomarkers of carcinogenesis and carcinogenic exposure in animal model, useful in human cancer prevention practice as well.

GSTM, GSTT and p53 polymorphisms as modifiers of clinical outcome in colorectal cancer.

BACKGROUND: Cancer of the colorectal region is the second most frequent cause of death among malignant diseases. The influence of two allelic polymorphisms of GSTM1 and GSTT1, and that of p53 gene codon 72 on colon cancer was investigated. PATIENTS AND METHODS: Intraoperatively removed tissue samples were processed from colorectal cancer patients. Cancer-free human samples were used as matched controls. Samples were digested with proteinase-K. DNA solution was used for PCR amplification. RESULTS: No significant difference was found between tumor patients and controls in the investigated polymorphisms. A significant association was found in Dukes' B stage patients between the GSTM1 and p53 gene variants and survival. In patients with GSTM1 null genotype and p53 Arg/Pro heterozygotes or Pro/Pro homozygotes the chance of survival is significantly lower than in the case of GSTM1+ and p53 Arg/Arg variants (p=0.009 and p=0.008, respectively). CONCLUSION: The significance of the investigated polymorphisms in prognosis is dependent on the tumor stage. These parameters might be used in certain cases as prognostic biomarkers in clinical diagnostics and in the planning of individual therapy.

Relationship between serum nickel and homocysteine concentration in hemodialysis patients.

Severe hyperhomocysteinemia (HHC) is associated with atherosclerosis. In hemodialysis (HD) patients, one of the main causes of death is cardiovascular disease. In animals, trace elements such as cobalt, copper, iron, and nickel ameliorated vitamin B(12) deficiency-induced HHC. However, correlations between plasma total homocysteine (tHcy) and trace elements in HD patients have not been investigated. Therefore, tHcy, folate, vitamin B(12), trace elements (cobalt, copper, iron, and nickel), and some laboratory parameters such as serum total protein, albumin, transferrin, ferritin, C-reactive protein (CRP), and interleukin-6 concentrations were determined in 122 hemodialysis patients. When patients were divided into groups according to their tHcy, we found no significant differences in concentrations of cobalt, copper, and total protein, while nickel was higher, and folate, vitamin B(12), and iron were lower in patients with lower than higher tHcy. In univariate regression analysis, tHcy negatively correlated with concentrations of folate (r = -0.302, p < 0.006), vitamin B(12) (r = -0.347, p < 0.0001), nickel (r = -0.289, p < 0.006), and CRP (r = -0.230, p < 0.02) and positively with serum albumin (r = 0.316, p < 0.0004) and hemoglobin (r = 0.329, p < 0.0001) values. No relationship between tHcy and serum concentrations of cobalt, copper, iron, or other laboratory parameters was found in HD patients. The effect of cobalt and nickel on homocysteine production was assessed in human peripheral mononuclear cells (PBMCs). Nickel but not cobalt at concentrations found in HD patients significantly inhibited homocysteine, cysteine, and S-adenosylhomocysteine production in human PBMCs. These results suggest that nickel might also be involved in the regulation of the methionine-folate cycle in humans, as was demonstrated in animal experiments.

[Omega-3 polyunsaturated fatty acids in the prevention of atherosclerosis]. / Az omega-3 többszörösen telítetlen zsírsavak az atherosclerosis megelôzésében.

Cardioprotective action of omega-3 polyunsaturated fatty acids such as eicosapentaenoic and docosahexaenoic acid in fish and alpha-linolenic acid in plants was demonstrated in primary and secondary clinical trials. Fish oil therapy causes a marked decrease in serum triacylglycerol and very low density lipoprotein levels and increases moderately high density lipoprotein levels without any adverse effects. Omega-3 fatty acids decrease slightly, but significantly blood pressure, enhance endothelial function, they have anti-aggregator, anti-thrombotic and anti-inflammatory effects as well. These beneficial effects are in connection with modification of gene transcription levels of some key molecules such as nuclear factor-kappaB and sterol element binding receptor protein-1c, which regulate for example expression of adhesion molecules or several receptors involved in triglyceride synthesis (hepatocyte X receptor, hepatocyte nuclear factor 4alpha, farnesol X receptor, and peroxisome proliferator-activated receptors). On the basis of these observations, the supplementation of the diet with omega-3 fatty acids (fish, fish oil, linseed, and linseed oil or canola oil) is advisable in primary and secondary prevention.

Early modification of c-myc, Ha-ras and p53 expressions by N-methyl-N-nitrosourea.

Methylnitrosourea (MNU) is a well-known pluripotent direct-acting carcinogen. Formation of MNU following incubation of various meats with additional nitrite under in vitro acidic conditions is possible. It is possible that many species, including humans, are exposed to carcinogenic MNU, generated in their alimentary tract. Previously, an animal model was developed by our research group to investigate the expression of three genes c-myc, Ha-ras and p53 as early molecular epidemiological biomarkers of carcinogenic exposure or carcinogenesis caused by DMBA (dimethylbenz[alpha]anthracene). The aim of this study was to investigate the early effect of MNU on the gene expression levels. MNU is a direct-acting carcinogen which spontaneously and rapidly degrades, so any effect on the gene expression is observed in 24 hours. Our results show the maximum effect in vivo on the gene expression at 12 hours after the MNU treatment; on the other hand, 24 hours after the treatment, the elevated gene expressions decreased in target organs (bone marrow, lung, lymph nodes). Our results correspond to "long-term" experiments of the carcinogenic effect of MNU in different target organs. Our findings suggest that MNU has an impact on the expression of c-myc, Ha-ras and p53 genes in 12 hours, especially in bone marrow. Overexpression of these genes occurs as an early biological effect of exposure to chemical carcinogens. According to our results, the high expression of these genes could indicate MNU exposure and these genes could take part in MNU-induced tumorigenesis.

Relationship of adiponectin to serum paraoxonase 1.

UNLABELLED: Correlation of the plasma levels of insulin-sensitizing, anti-inflammatory and anti-atherosclerotic adiponectin with HDL has been demonstrated. However, its relation to HDL-bound paraoxonase 1 (PON1) has not been clarified. The association of serum PON1 activity with findings of metabolic syndrome was investigated in three age and sex-matched groups: (1) non-diabetic overweight subjects with BMI 28-39.9 kg/m(2) (n=25); (2) non-diabetic obese subjects with BMI>or=40 kg/m(2) (n=25); and (3) healthy, normal-weight controls (n=24). Of the parameters investigated, PON1 activity correlated positively with concentrations of HDL-C and adiponectin, and correlated negatively with BMI, waist circumference, systolic BP, levels of HbA(1C), and insulin, HOMA-IR, and TBARS. The positive correlation between adiponectin and PON1 remained significant even after adjustments for age, gender, BMI, blood pressure, HOMA-IR, HDL-C, LDL-C, and lipid peroxidation. CONCLUSIONS: PON1 activity shows negative association with markers of metabolic syndrome. We demonstrate that adiponectin is an independent variable of serum PON1, which may contribute to the anti-atherosclerotic effect of adiponectin.

Effects of tocopherols and 2,2'-carboxyethyl hydroxychromans on phorbol-ester-stimulated neutrophils.

Tocopherol vitamers [e.g., alpha-, gamma- and delta-tocopherol (alpha-TOC, gamma-TOC and delta-TOC, respectively)] and their water-soluble 2,2'-carboxyethyl hydroxychroman metabolites (e.g., alpha-, gamma- and delta-CEHC) all possess antioxidant properties. As a consequence, and similarly to other natural antioxidants, vitamin E compounds may be useful in preventing inflammatory and oxidative-stress-mediated diseases. In this study, we investigated the concentration-dependent effect of tocopherols and water-soluble metabolites on a key event in oxidative stress, for example, the oxidative burst in neutrophils. It was found that not only alpha-TOC but also gamma-TOC and delta-TOC as well as alpha-, gamma- and delta-CEHC at physiological concentrations inhibit superoxide anion (O2(*-)) production in phorbol-ester-stimulated neutrophils. This effect was mediated by the inhibition of the translocation and activation of protein kinase C (PKC) enzyme, which is the key event in the phorbol-ester signaling. Importantly, CEHCs were stronger inhibitors of PKC as compared with the vitamer precursors, and the gamma forms of both tocopherol and CEHC showed the highest inhibitory activities. Tocopherols, but not CEHCs, directly inhibit the fully activated nicotine-adenine-dinucleotide phosphate (NADPH) oxidase. However, none of the test compounds was able to directly scavenge O2(*-) when tested in a cell-free system. In conclusion, vitamin E compounds can control the neutrophil oxidative burst through the negative modulation of PKC-related signaling and NADPH oxidase activity. As an original finding, we observed that CEHC metabolites might contribute to regulate PKC activity in these cells. These results may have important implications in the anti-inflammatory and antioxidant role of vitamin E compounds.

Relationship of endogenous hyperleptinemia to serum paraoxonase 1, cholesteryl ester transfer protein, and lecithin cholesterol acyltransferase in obese individuals.

Altered activities of high-density lipoprotein (HDL)-associated antioxidant enzyme paraoxonase 1 (PON1) and lipid transfer proteins, for example, cholesteryl ester transfer protein (CETP) and lecithin cholesterol acyltransferase (LCAT), participating in lipoprotein remodeling seem to play important roles in obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum leptin levels have been demonstrated. However, the relationship of leptin with CETP and LCAT in humans is less clear. Our aims were to investigate whether the elevated leptin level is (a) an independent predictor of low PON1 and (b) associated with alterations of CETP and LCAT activities. Seventy-four white subjects forming 3 age- and sex-matched groups were included into the study (groups 1 and 2: nondiabetic obese patients, n = 25 with body mass index [BMI] 28-39.9 kg/m2 and n = 25 with BMI >or=40 kg/m2, respectively; and group 3: 24 healthy, normal-weight control subjects). Paraoxonase 1 correlated inversely with BMI (r = -0.39, P < .01), waist circumferences (r = -0.42, P < .001), and leptin concentrations (r = -0.38, P < .001). However, in a multiple regression model, neither these variables nor others, for example, age, sex, blood pressure, insulin resistance (in homeostasis model assessment of insulin resistance [HOMA-IR]), HDL cholesterol, low-density lipoprotein cholesterol, or lipid peroxidation (measured as thiobarbituric acid reactive substances), proved to be independent predictors of PON1. Lecithin cholesterol acyltransferase correlated negatively with BMI (r = -0.40, P < .01), waist circumferences (r = -0.42, P < .001), and leptin levels (r = -0.40, P < .01). During multiple regression analyses, BMI was an independent predictor of LCAT after adjustments for age, sex, HOMA-IR, and HDL cholesterol. However, this was replaced by leptin and HOMA-IR when leptin was also included into the model. The CETP activities correlated with HOMA-IR (r = 0.33, P < .01), thiobarbituric acid reactive substances (r = 0.45, P < .001), and leptin (r = 0.36, P < .01) levels in univariate but not in multivariate models. Elevated leptin level is an independent predictor of low LCAT, but not PON1, activity. In a population with a wide range of BMI, LCAT correlates inversely with obesity and CETP directly with insulin resistance.