Long-term use of prescription opioids for non-cancer pain and mortality: a population-based, propensity-weighted cohort study.

OBJECTIVE: The objective of this study was to identify factors associated with long-term opioid use and to assess the association between long-term use and death. STUDY DESIGN: Retrospective cohort study combining several population-wide databases and covering a population of five million inhabitants, including all adults who were initiated on opioid treatment from 2014 to 2018 for non-cancer pain. METHODS: We used logistic regression models to identify factors associated with chronic opioid use and carried out survival analyses using multivariable Cox regression modelling for all-cause mortality during follow-up using inverse probability of treatment weighting (IPTW) and propensity scores based on the probability of using opioids chronically. RESULTS: Among 760,006 patients, 82,423 (10.85%) used opioids for 90 days or more after initiation. Initial therapy characteristics associated with higher risk for long-term use were initiating with long- and short-acting opioids (when compared to tramadol, odds ratio [OR]: 2.63, 95% confidence interval [CI]: 2.57, 2.69 and OR: 1.60, 95%CI: 1.46, 1.76, respectively), using higher daily doses (when compared to 50 morphine milligramme equivalent [MME] or less, prescribing 50 to 89 daily MME, OR: 1.76, 95%CI: 1.65, 1.87; 90 to 119 daily MME, OR: 2.44, 95%CI: 1.99, 3.01; and more than 120 daily MME, OR: 1.77, 95%CI: 1.64, 1.91), and overlapping with gabapentinoids (OR: 2.26, 95%CI: 2.20, 2.32), benzodiazepines (OR: 1.32, 95%CI: 1.30, 1.35), and antipsychotics (OR: 1.21, 95%CI: 1.16, 1.26). After IPTW, chronic opioid use was associated with higher risk of all-cause mortality when compared to short-term use (Hazard Ratio (HR): 1.37, 95%CI: 1.32, 1.42). Sensitivity analyses provided similar results. CONCLUSION: These findings may help healthcare managers to identify and address patients at higher risk of long-term use and riskier prescription patterns.

Glucocerebrosidase (GCase) activity modulation by 2-alkyl trihydroxypiperidines: Inhibition and pharmacological chaperoning.

The enzyme glucocerebrosidase (GCase) has become an important therapeutic target due to its involvement in pathological disorders consequent to enzyme deficiency, such as the lysosomal storage Gaucher disease (GD) and the neurological Parkinson disease (PD). Pharmacological chaperones (PCs) are small compounds able to stabilize enzymes when used at sub-inhibitory concentrations, thus rescuing enzyme activity. We report the stereodivergent synthesis of trihydroxypiperidines alkylated at C-2 with both configurations, by means of the stereoselective addition of Grignard reagents to a carbohydrate-derived nitrone in the presence or absence of Lewis acids. All the target compounds behave as good GCase inhibitors, with IC50 in the micromolar range. Moreover, compound 11a behaves as a PC in fibroblasts derived from Gaucher patients bearing the N370/RecNcil mutation and the homozygous L444P mutation, rescuing the activity of the deficient enzyme by up to 1.9- and 1.8-fold, respectively. Rescues of 1.2-1.4-fold were also observed in wild-type fibroblasts, which is important for targeting sporadic forms of PD.

Review and update on drugs related to the development of osteonecrosis of the jaw.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but serious adverse effect of certain drugs, of which bisphosphonates are the most widely known. This pathology is also associated with other medications such as the biologic antiresorptive agent, denosumab and some antiangiogenics such as sunitinib, bevacizumab or aflibercept. Very recently, new medications have also been associated with osteonecrosis of the jaw (ONJ). The objectives were to update the list of medications associated with ONJ, to analyze the fundamental aspects of this list and to describe the level of evidence available. MATERIAL AND METHODS: A narrative bibliographic review was made, using the PubMed-MedLine, DOAJ and SCIELO databases. Additional information was obtained through the online Medication Information Centre of the Spanish Agency of Medicines and Medical Devices (AEMPS - CIMA), the websites of the US Food & Drugs Administration (Drugs@FDA) and the European Medicines Agency (EMA). RESULTS: The latest drugs identified as potential facilitators of this pathology include a number of anti-VEGF based antiangiogenic drugs and anti-TKI and different types of immunomodulators. Neither the level of evidence in this association nor the risk are equal for all these drugs. On the other hand, over the coming years, new drugs will be marketed with similar action mechanisms to those that are recognized as having this adverse effect. CONCLUSIONS: No effective therapy is currently known for the treatment of ONJ. Therefore, in order to prevent new cases of MRONJ, it is essential for all oral healthcare professionals to be fully up-to-date with the etiopathogenic aspects of this pathology and to be aware of those drugs considered to be a risk.

Antibodies to neuronal surface proteins in Tourette Syndrome: Lack of evidence in a European paediatric cohort.

In Tourette Syndrome (TS) a role for autoantibodies directed against neuronal proteins has long been suspected, but so far results are still inconsistent. The aim of this study was to look for antibodies to specific or undefined neuronal proteins that could be involved in the aetiology of the disease. Sera from children with Tourette Syndrome or another chronic tic disorder (TS/TD), collected as part of the longitudinal European Multicenter Tics in Children Study, were investigated. Participants included 30 siblings of patients with TS/TD prior to developing tics (preclinical stage) and the same children after the first tic onset (onset), and 158 patients in the chronic phase undergoing an acute relapse (exacerbation). Presence of antibodies binding to rodent brain tissue was assessed by immunohistology on rat brain sections and by immunofluorescent staining of live hippocampal neurons. Live cell-based assays were used to screen for antibodies to NMDAR, CASPR2, LGI1, AMPAR and GABAAR. Immunohistology indicated evidence of antibodies reactive with brain tissue, binding mainly to the hippocampus, the basal ganglia or the cerebellum in 26/218 (12%), with 8% of the preclinical or onset sera binding to the dentate gyrus/CA3 region or cerebellum. Only two individuals (one pre-clinical, one chronic) had antibodies binding the NMDAR and the binding was only weakly positive. No other specific antibodies were detected. Despite some immunoreactivity towards neuronal antigens on brain tissue, this was not mirrored by antibodies binding to live neurons, suggesting the presence of non-specific antibodies or those that bind non-pathogenic intracellular epitopes. NMDAR or the other neuronal surface antibodies tested were very infrequent in these patients. The evidence for pathogenic antibodies that could be causative of TS is weak.

Multimerization of DAB-1 onto Au GNPs affords new potent and selective N-acetylgalactosamine-6-sulfatase (GALNS) inhibitors.

Gold glyconanoparticles (Au GNPs) decorated with the natural iminosugar DAB-1 at different densities are reported. These new multivalent iminosugar architectures strongly and selectively inhibit N-acetylgalactosamine-6-sulfatase (GALNS), whose deficiency is connected to the lysosomal storage disease Morquio A. The combination of the dendrimeric technique with the synthetic strategy employed for Au GNP preparation allowed the enhancement of the multivalent presentation of the iminosugar onto the surface of gold nanoparticles, which resulted in the best GALNS inhibitor reported to date (IC50 = 520 nM).

Molecular effect of fenofibrate on PBMC gene transcription related to lipid metabolism in patients with metabolic syndrome.

BACKGROUND: Both fasting and postprandial hypertriglyceridaemia are considered independent risk factors for atherosclerosis. Treatment of hypertriglyceridaemia is based on fibrates, which activate the peroxisome proliferator-activated receptor alpha (PPARα). However, the metabolic pathways that activate or inhibit fibrates, and how the postprandial triglyceride levels are modified, have not yet been fully described. Accordingly, the aim of this study was to determine the feasibility of peripheral blood mononuclear cells (PBMC) to study the effects of fenofibrate in patients with the metabolic syndrome. MATERIALS AND METHODS: A fat overload was given to 50 patients before and after treatment with fenofibrate for 3 months. Anthropometric and biochemical variables as well as gene expression in PBMC were analysed. RESULTS: After treatment with fenofibrate, we observed a decrease in both baseline and postprandial (3 h after the fat overload) levels of serum triglycerides, cholesterol and uric acid and an increase in HDL cholesterol and apolipoprotein AI levels. After treatment, there was also a rise in PPARα and RXRα expression and changes in genes regulated by PPARα, both baseline and postprandial. Furthermore, in vitro experiments showed that a PPARα agonist changed the expression of genes related with lipid metabolism. CONCLUSION: Treatment with fenofibrate reduced fasting and postprandial serum triglyceride levels, possibly through a mechanism related with an increase in the expression of RXRα and PPARα, by activating the pathways involved in the uptake and degradation of triglycerides and increasing the synthesis of apolipoprotein. These results suggest that PBMC may be useful for the easy study of fenofibrate actions.

Accessing 2-substituted piperidine iminosugars by organometallic addition/intramolecular reductive amination: aldehyde vs. nitrone route.

A dual synthetic strategy to afford 2-substituted trihydroxypiperidines is disclosed. The procedure involved Grignard addition either to a carbohydrate-derived aldehyde or to a nitrone derived thereof, and took advantage of an efficient ring-closure reductive amination strategy in the final cyclization step. An opposite diastereofacial preference was demonstrated in the nucleophilic attack to the two electrophiles, which would finally produce the same piperidine diastereoisomer as the major product. However, use of a suitable Lewis acid in the Grignard addition to the nitrone allowed reversing the selectivity, giving access to 2-substituted piperidines with the opposite configuration at C-2.

BDNF and LTP-/LTD-like plasticity of the primary motor cortex in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (GTS) is characterized by motor and vocal tics and often associated with obsessive-compulsive disorder (OCD). Responses to intermittent/continuous theta-burst stimulation (iTBS/cTBS), which probe long-term potentiation (LTP)-/depression (LTD)-like plasticity in the primary motor cortex (M1), are reduced in GTS. ITBS-/cTBS-induced M1 plasticity can be affected by brain-derived neurotrophic factor (BDNF) polymorphism. We investigated whether the BDNF polymorphism influences iTBS-/cTBS-induced LTP-/LTD-like M1 plasticity in 50 GTS patients and in 50 age- and sex-matched healthy subjects. In GTS patients, motor and psychiatric (OCD) symptom severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). We compared M1 iTBS-/cTBS-induced plasticity in healthy subjects and in patients with GTS. We also compared responses to TBS according to BDNF polymorphism (Val/Val vs Met carriers) in patients and controls. Fourteen healthy subjects and 13 GTS patients were Met carriers. When considering the whole group of controls, as expected, iTBS increased whereas cTBS decreased MEPs. Differently, iTBS/cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS. When comparing responses to TBS according to BDNF polymorphism, in healthy subjects, Met carriers showed reduced MEP changes compared with Val/Val individuals. Conversely, in patients with GTS, responses to iTBS/cTBS were comparable in Val/Val individuals and Met carriers. YGTSS and Y-BOCS scores were comparable in Met carriers and in Val/Val subjects. We conclude that iTBS and cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS, and this was not affected by BDNF genotype.

From glycals to aminosugars: a challenging test for new stereoselective aminohydroxylation and related methodologies.

The introduction of amino functionalities in a regio- and stereoselective manner onto sugar scaffolds represents a great challenge in carbohydrate synthesis. The most relevant methods to access 1-, 2-, 3-amino or 1,2-diaminosugars starting from glycals and 2,3-hexenopyranosides derived from them are concisely reviewed. The main synthetic strategies for accessing this class of compounds are classified in intermolecular and intramolecular approaches and the key features of each class are discussed. This review highlights how carbohydrate derivatives always pose great challenges representing a benchmark for assessing the efficiency of stereoselective strategies, and aims to give the readers inspiration for the development of new procedures.

Management of hypothermia for perinatal asphyxia in Austria - a survey of current practice standards.

BACKGROUND: Therapeutic hypothermia (HT) has been shown to reduce the risk of death or disability and increase the rate of survival free of -disability at 18-24 months of age in hypoxic-ischemic encephalopathy (HIE). OBJECTIVES: The aim of this study was to take a national survey which (a) evaluated the practice of therapeutic HT for perinatal asphyxia in Austria, (b) evaluated the current clinical management of neonatal HIE and (c) evaluated the need for a national perinatal asphyxia and HT registry. METHODS: In January 2013, a questionnaire was sent out to the clinical heads of all neonatal level-II and level-III units in Austria. RESULTS: We received replies from all 30 level II and level III units in Austria (response rate 100%). 19 units (63%) answered that they applied HT, 11 units (37%) said they transferred patients for cooling to other units, 3 of those 11 units (27%) said they applied cooling during transport. 25 units (83%) felt the necessity to establish a national registry. CONCLUSION: The results of this survey show that there is already a high implementation of therapeutic HT in Austria, but there remains a need for information, awareness and training. Problem areas tend to be in the transport of asphyxiated neonates, brain monitoring during cooling and follow-up of affected patients. We believe, that the establishment of national guidelines and a national register could increase awareness for the importance of therapeutic HT in neonatal HIE, thus improve the Austrian management of those infants.

Blood transfusions using 27 gauge PICC lines: a retrospective clinical study on safety and feasibility.

BACKGROUND: Blood transfusions are required by most extremely low birth weight (ELBW) infants, but sometimes an adequate peripheral venous access cannot be achieved. Under these circumstances, we used 27 Gauge (G) peripherally inserted central catheter (PICC) lines that are routinely inserted on the second day of life. Due to their narrow lumen, hemolysis of transfused erythrocytes was a major concern. We therefore performed a retrospective study in ELBW infants to analyze the incidence, safety and feasibility of PRBC transfusions via 27 G PICC lines. METHODS: ELBW infants admitted from 08/2011-07/2012 were screened for packed red blood cell (PRBC) transfusions. Those applied via 27 G PICC lines were identified. For analysis of transfusion safety (hemolysis), hemoglobin and potassium levels as well as cardiovascular variables (invasive mean arterial blood pressure and heart rate) were evaluated before and after transfusion. For analysis of transfusion feasibility, catheter removal after transfusion and the reason for removal were recorded. RESULTS: A total of 648 transfusions were applied in 110 ELBW infants. 27 infants (24%) received no transfusion. In 12/83 (14.5%) infants who received PRBCs, transfusions were applied using a 27 G PICC line (38/648, 5.9%). Patients who received PRBCs via the PICC line were smaller at birth (582 g [range 380-752 g] vs. 710 g [430-972 g]; 23+6 [23+1-27+6] vs. 26+0 [23+1-31+4]) and required a higher number of PRBC transfusions (n=13 vs. n=5) overall. Transfusion analysis showed an appropriate increase of blood hemoglobin levels and stable potassium levels as well as cardiovascular parameters. 4/38 of PICC lines were removed within 24 h after transfusion, one due to occlusion (15 h after transfusion). CONCLUSIONS: We conclude that PRBC transfusions via 27 G PICC lines were feasible and performed without signs of hemolysis in ELBW infants. Our findings may help clinicians in the management of ELBW infants requiring transfusions if a peripheral venous access is not achievable.

Safety of blood transfusions using 27 gauge neonatal PICC lines: an in vitro study on hemolysis.

Blood transfusions are required by the majority of extremely premature infants. Packed red blood cells (PRBCs) are usually applied via simple peripheral cannulas. In situations where no peripheral venous access is achievable, 27 Gauge (G) neonatal PICC lines - that are ideally exclusively dedicated to application of parenteral nutrition - may represent a useful alternative access for PRBC transfusions. However, transfusion via small scaled catheters may damage PRBCs and lead to hemolysis. We here evaluate whether transfusion of irradiated PRBCs via 27 G PICC lines leads to hemolysis in vitro.Experimental transfusions of gamma-irradiated PRBCs were performed at increasing velocities (2.5, 3.7, 5 ml/h; full force manual push approximating 30 ml/h) via 27 G PICC lines of 20 and 30 cm length. Parameters of hemolysis (lactate dehydrogenase, potassium and free hemoglobin) were measured from the supernatants of transfused PRBCs and the percentage of hemolysis was calculated.Potassium and lactate dehydrogenase after transfusion at increasing velocities did not differ significantly from negative controls. Free hemoglobin levels showed a small but significant increase at the slowest transfusion speed (2.5 ml/h) using the 30 cm 27 G PICC line, with a relative hemolysis of only 0.13%. A manual push (approximating 30 ml/h) showed no significant changes of parameters from baseline.We conclude that transfusion of gamma-irradiated PRBCs using a 27 G neonatal PICC line does not cause clinically relevant hemolysis in vitro. Clinical studies are needed to confirm the feasibility and safety of the approach in vivo.

Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients.

The low-grade inflammation observed in obesity has been associated with a high-fat diet, though this relation is not fully understood. Bacterial endotoxin, produced by gut microbiota, may be the linking factor. However, this has not been confirmed in obese patients. To study the relationship between a high-fat diet and bacterial endotoxin, we analyzed postprandial endotoxemia in morbidly obese patients after a fat overload. The endotoxin levels were determined in serum and the chylomicron fraction at baseline and 3 h after a fat overload in 40 morbidly obese patients and their levels related with the degree of insulin resistance and postprandial hypertriglyceridemia. The morbidly obese patients with the highest postprandial hypertriglyceridemia showed a significant increase in lipopolysaccharide (LPS) levels in serum and the chylomicron fraction after the fat overload. Postprandial chylomicron LPS levels correlated positively with the difference between postprandial triglycerides and baseline triglycerides. There were no significant correlations between C-reactive protein (CRP) and LPS levels. The main variables contributing to serum LPS levels after fat overload were baseline and postprandial triglyceride levels but not glucose or insulin resistance. Additionally, superoxide dismutase activity decreased significantly after the fat overload. Postprandial LPS increase after a fat overload is related to postprandial hypertriglyceridemia but not to degree of insulin resistance in morbidly obese patients.

Assessment of cellular and plasma oxidative stress in SAHS patients before and after continuous positive airway pressure treatment.

BACKGROUND: Several indirect techniques have been used for measuring oxidative stress in sleep apnoea-hypopnoea syndrome (SAHS) patients. The purpose of this study was to find out if both, cellular or plasma oxidative stress evaluations, are good estimators to assess oxidative stress in SAHS patients before and after one month's CPAP treatment. METHODS: The study included 28 SAHS patients requiring CPAP treatment and 15 healthy control subjects. Plasma and serum oxidative stress biomarkers (lipid peroxidation, total antioxidant capacity, and the activities of glutathione peroxidase, glutathione reductase, glutathione s-transferase, catalase and superoxide dismutase) were measured using commercial kits. Cellular oxidative stress biomarkers (mitochondrial membrane potential, intracellular glutathione, superoxide anion, and hydrogen peroxide) were analysed by flow cytometry. The Wilcoxon test for paired samples was used to compare oxidative stress and clinical parameters in patients before and after treatment with CPAP. Relationships in oxidative stress markers between controls and patients were analyzed using the Mann-Whitney U test. The Spearman correlation coefficient was calculated to estimate the linear correlations between variables. RESULTS: Oxidative stress was notably decreased after CPAP. Before CPAP, SAHS severity positively correlated with hydrogen peroxide levels, while negative correlations were observed between SAHS severity and plasma TAC in patients. Also, plasma glutathione peroxidase activity negatively correlated with cellular superoxide anion, while plasma superoxide dismutase activity positively correlated with intracellular glutathione. After CPAP, plasma TAC and glutathione peroxidase activity negatively correlated with cellular hydrogen peroxide and superoxide anion. CONCLUSIONS: In conclusion, this study seems to confirm that plasma and cellular assessment reflect, in the same way, the oxidative stress status of the studied patients. Furthermore, plasma total antioxidant capacity as well as cellular hydrogen peroxide levels can be good markers for assessing oxidative stress in SAHS patients.

Ubiquitin ligase Rsp5p is involved in the gene expression changes during nutrient limitation in Saccharomyces cerevisiae.

Rsp5p is an essential ubiquitin ligase involved in many different cellular events, including amino acid transporters degradation, transcription initiation and mRNA export. It plays important role in both stress resistance and adaptation to the change of nutrients. We have found that ubiquitination machinery is necessary for the correct induction of the stress response SPI1 gene at the entry of the stationary phase. SPI1 is a gene whose expression is regulated by the nutritional status of the cell and whose deletion causes hypersensitivity to various stresses, such as heat shock, alkaline stress and oxidative stress. Its regulation is mastered by Rsp5p, as mutations in this gene lead to a lower SPI1 expression. In this process, Rsp5p is helped by several proteins, such as Rsp5p-interacting proteins Bul1p/2p, the ubiquitin conjugating protein Ubc1p and ubiquitin proteases Ubp4p and Ubp16p. Moreover, a mutation in the RSP5 gene has a global effect at the gene expression level when cells enter the stationary phase. Rsp5p particularly controls the levels of the ribosomal proteins mRNAs at this stage. Rsp5p is also necessary for a correct induction of p-bodies under stress conditions, indicating that this protein plays an important role in the post-transcriptional fate of mRNA under nutrient starvation.

Anti-oxidized LDL antibody levels are reduced in women with hypertension.

BACKGROUND: Previous studies have suggested that hypertension may be associated with increased oxidized low-density lipoprotein (LDL). Increased in vitro oxidizability of LDL or elevated titers of anti-oxidized LDL antibodies have been shown in subjects with essential hypertension. However, the relationship between oxidized LDL and hypertension is equivocal. We examined the association between hypertension and levels of IgG anti-oxidized LDL antibodies in a group of women from the general population. MATERIALS AND METHODS: The study included 619 women classified according to their blood pressure values. IgG anti-oxidized LDL antibodies were measured by enzyme-linked immunosorbent assay and the women were classified as being above or below the 50th percentile. RESULTS: Hypertension was present in 54.3% of the women. These women had significantly lower levels of IgG anti-oxidized LDL antibodies than the normotensive women (0.280 +/- 0.117 vs. 0.336 +/- 0.125, P < 0.001). Both systolic and the diastolic blood pressures showed a significant negative correlation with the levels of IgG anti-oxidized LDL antibodies (r = -0.204, P < 0.001; r = -0.225, P < 0.001, respectively). Women with IgG anti-oxidized LDL antibody levels above the 50th percentile had a lower prevalence of hypertension than those with IgG anti-oxidized LDL antibody levels below the 50th percentile (40.2% vs. 59.8%) (P < 0.001). CONCLUSIONS: Women with hypertension had lower levels of IgG anti-oxidized LDL antibodies than normotensive women.

Fat overload aggravates oxidative stress in patients with the metabolic syndrome.

BACKGROUND: Patients with the metabolic syndrome have greater levels of oxidative stress. However, as the response of markers of this stress to a fat overload is unknown, we evaluated certain markers of oxidative stress in these patients. MATERIAL AND METHODS: The study population comprised 93 subjects (70 men and 23 women): 13 healthy people (controls) with a mean age of 48.81 +/- 9.01 years and 80 patients with the metabolic syndrome (mean age, 43.25 +/- 11.55 years), according to the Adult Treatment Panel III criteria. All the participants were given a 60 g fat overload (Supracal). Three hours later the following biomarkers of oxidative stress were measured: lipid peroxidation products, protein carbonyl groups, reduced glutathione, glutathione peroxidase (GSH-Px), catalase, superoxide dismutase, glutathione reductase (GSH-Road) and glutathione S-transferase. The levels of oxidized glutathione (GSSG) were calculated. RESULTS: Compared with the controls, the patients showed greater baseline oxidative stress, higher levels of lipid peroxidation products and oxidized glutathione, and lower levels of reduced glutathione, glutathione peroxidase activity, glutathione reductase and glutathione transferase. This stress was more intense after the subjects received a fat overload, more so in the patients who experienced a greater reduction in GSHpx and GSHrd antioxidant activity and a greater increase in the levels of carbonylated proteins and lipoperoxides than the controls. CONCLUSIONS: Patients with the metabolic syndrome have greater oxidative stress than healthy people. The variation in markers of this stress after a fat overload was even more pronounced in the patients.

Anti-oxidized low-density lipoprotein antibody levels are associated with the development of type 2 diabetes mellitus.

BACKGROUND: Anti-oxidized low-density lipoprotein (LDL) antibodies are associated with the oxidative capacity of plasma, but whether they protect or promote diabetes is unknown. We undertook a prospective study to determine the predictive capacity of anti-oxidized LDL antibodies for the onset of type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We selected 391 non-diabetic women aged 18-65 years. The subjects were classified as being normal (oral glucose test tolerance normal, OGTT-N), or having impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or T2DM according to their baseline glucose levels and after an OGTT. The same subjects were studied six years later. The levels of anti-oxidized LDL antibodies were classified as above or below the 50th percentile. RESULTS: Of the women who were OGTT-N at the start of the study and who had anti-oxidized LDL antibody levels below the 50th percentile, only 65.1% were still OGTT-N after 6 years versus 79.5% of those who had anti-oxidized LDL antibody levels above the 50th percentile (P = 0.015). Women who had IGT or IFG at the start of the study whose anti-oxidized LDL antibody levels were below the 50th percentile had a relative risk of 9.79 (95% confidence interval, 1.40-68.45) of developing diabetes (P < 0.001). Logistic regression analysis showed that the variables predicting the development of a carbohydrate metabolism disorder in the women after 6 years were body mass index (P < 0.001) and the levels of anti-oxidized LDL antibodies (P = 0.042). CONCLUSIONS: Levels of anti-oxidized LDL antibodies are independent predictors for the development of T2DM in women.

Green tea reduces LDL oxidability and improves vascular function.

OBJECTIVE: Several different epidemiological studies have examined the association between the consumption of tea and coronary heart disease. Some, though not all, support the view that tea or flavonoids reduce the risk of cardiovascular heart disease. The aim of this study was to determine the short-to medium-term effect of a green tea extract on vascular function and lipid peroxidation as compared with placebo. METHODS: The study was undertaken with 14 healthy women, none of whom were receiving any medical treatment. Measurements were made of antibodies and immune complexes by ELISA, endothelial dependent vascular function by Doppler ultrasound, and the concentration of oxidized LDL by TBARS. RESULTS: The mean diameter of the brachial artery following the post-compression hyperaemia phase rose significantly (p < 0.0001) after treatment with green tea extract. Flow-mediated brachial artery vasodilation ranged from 5.68% for the placebo phase to 11.98% after the green tea extract (p = 0.02). The consumption of green tea extract was associated with a significant 37.4% reduction in the concentration of oxidized LDL (TBARS) (p = 0.017). The levels of anti-oxidized LDL IgM antibodies fell significantly after treatment (p = 0.002). CONCLUSION: This study found that consumption of green tea extract by women for five weeks produced modifications in vascular function and an important decrease in serum oxidizability.