Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus

ObjectivesTo find whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among type 2 diabetes mellitus (T2DM) patients from Western Iran.Design and methodsThe MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric T2DM patients by PCR-RFLP.ResultsThe possession of both MTHFR 677T and 1298C alleles increase the risk of microalbuminuria to 4.3-fold (p = 0.007) in T2DM patients. The presence of either MTHFR 677T, 1298C allele is sufficient to increase the risk of macroalbuminuria in T2DM patients by 4.1 and 5.5 times (p = 0.027, and p = 0.006, respectively). The concomitant presence of both 677T and 1298C alleles act in synergy to increase the risk of macroalbuminuria by 20.4-fold (p < 0.001) and progression of DN from microalbuminuria to macroalbuminuria (OR = 4.73, p = 0.01).ConclusionBoth MTHFR 677T and 1298C alleles increased the susceptibility to the onset and progression of DN in Iranians with T2DM.     

Increased large VLDL and small LDL particles are related to lower bilirubin in Type 2 diabetes mellitus

ObjectivesBilirubin may protect against atherosclerotic cardiovascular disease by virtue of its anti-oxidative properties, but lower bilirubin may also be associated to atherogenic lipoprotein abnormalities. We determined associations of plasma (apo)lipoproteins and lipoprotein subfractions in subjects with and without type 2 diabetes mellitus (T2DM).Design and methodsPlasma (apo)lipoproteins, lipoprotein subfractions (nuclear magnetic resonance spectroscopy) and serum total bilirubin levels were determined in 53 T2DM patients and in 53 non-diabetic subjects.ResultsTriglycerides, large VLDL, small LDL and small HDL particles were increased (all p < 0.05), whereas HDL cholesterol, apoA-I and large HDL particles were decreased (all p < 0.05), coinciding lower bilirubin levels in T2DM (p < 0.001). In age- and sex-adjusted analysis, total cholesterol, non-HDL cholesterol, triglycerides, apoB, apoE, large VLDL and small LDL were negatively correlated with bilirubin, but HDL cholesterol was positively correlated with bilirubin in T2DM (p < 0.05 to p < 0.001). Multivariable linear regression analyses demonstrated that in all subjects combined total cholesterol, non-HDL cholesterol, triglycerides and apoE were negatively associated with bilirubin after adjustment for age, sex, T2DM, body mass index and alanine aminotransferase (all p < 0.05). Further multivariable linear regression analysis showed that large VLDL and small LDL particles were negatively associated with bilirubin, whereas large HDL particles were associated positively with bilirubin (p < 0.05).ConclusionsIncreased triglycerides, as well as large VLDL and small LDL particles are associated negatively, whereas HDL cholesterol is associated positively with bilirubin in T2DM. The proposed pro-atherogenic effects of low bilirubin could in part be attributed to relationships with abnormalities in (apo)lipoproteins and lipoprotein subfraction characteristics.     

Association of vascular indices with novel circulating biomarkers as prognostic factors for cardiovascular complications in patients with type 2 diabetes mellitus

BackgroundThe pathophysiology of atherosclerosis in type 2 diabetes mellitus (T2DM) is multifactorial. The association of vascular indices with circulating biomarkers of inflammation and insulin resistance and their role in the long-term cardiovascular prognosis in T2DM patients were currently investigated.Patients and methodsPatients with T2DM and poor glycemic control without known cardiovascular diseases (n = 119) at baseline were enrolled and followed for about 9 years. The end-point was the occurrence of any cardiovascular event (coronary heart disease, stroke, peripheral artery disease or cardiovascular death). Aortic pulse wave velocity (PWV), augmentation index (AIx), brachial flow-mediated dilation (FMD), hsCRP, Chitinase-3-like protein 1 (YKL-40), Neutrophil Gelatinase-Associated Lipocalin (NGAL), Fatty Acid Binding Protein (FABP-4) were assessed.ResultsHigher YKL-40 and NGAL were associated with higher PWV, while higher YKL-40 and FABP-4 were related to higher AIx (p < 0.05 for all). In univariate Cox regression analysis, PWV > 10 m/s, YKL-40 > 78 ng/ml and NGAL > 42 ng/ml were associated with cardiovascular events (p < 0.05 for all). In multivariate analysis, after adjusting for classical risk factors and glycemic control, increased NGAL, YKL-40 and PWV and decreased FMD (i.e. ≤ 2.2%) (p < 0.05 for all) were independently associated with cardiovascular events.ConclusionIn T2DM patients without established cardiovascular disease, novel indices of vascular inflammation (NGAL and YKL-40) were associated with subclinical atherosclerosis (arterial stiffness) but also with adverse clinical prognosis. Arterial stiffness and endothelial dysfunction were also independently related to adverse prognosis.     

HDL 2 Particles are associated with hyperglycaemia,lower PON1 activity and oxidative stress in type 2 diabetes mellitus patients

ObjectivesIn this study we examined the relationship of oxidative stress and hyperglycaemia to antioxidative capacity of high-density cholesterol (HDL-C) particles in type 2 diabetes mellitus (DM).Design and methodsOxidative stress status parameters (superoxide anion (O₂^?), superoxide dismutase (SOD) activity and paraoxonase (PON1) status were assessed in 114 patients with type 2 DM and 91 healthy subjects. HDL particle diameters were determined by non-denaturing polyacrylamide gradient (3–31%) gel electrophoresis.ResultsPatients had significantly higher concentrations of oxidative stress parameter O₂^?(p < 0.001) and antioxidative defence, SOD activity (p < 0.001). Paraoxonase activity was significantly lower in diabetics (p < 0.001). The PON1₁₉₂ phenotype distribution among study groups was not significantly different. HDL 3 phenotype was significantly prevalent among patients (p < 0.001). Paraoxonase activity was significantly lower in patients with predominantly HDL 2 particles than in controls.ConclusionsThe results of our current study indicate that the diabetic HDL 2 phenotype is associated with hyperglycaemia, lower PON1 activity and elevated oxidative stress.     

Minor association of kinase insert domain-containing receptor gene polymorphism (rs2071559) with myocardial infarction in Caucasians with type 2 diabetes mellitus: Case–control cross-sectional study

ObjectiveVascular endothelial growth factor A (VEGF) and its receptor KDR play central roles in angiogenesis and vascular repair, which occur in diabetic vascular complications, such as MI. The aim of our study was to investigate if polymorphisms rs2071559 and rs2305948 in the kinase insert domain-containing receptor (KDR) gene are associated with myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM).Design and methodsThe association of KDR − 604T>C (rs2071559) and 1192G>A (rs2305948) polymorphisms was tested in a case–control cross-sectional study including 171 subjects with T2DM and MI compared to 855 subjects with T2DM without coronary artery disease (CAD). In addition, VEGF serum levels were analyzed in 98 subjects with type 2 diabetes without CAD.ResultsA significantly higher frequency of the CC genotype of the KDR − 604T>C (rs2071559) polymorphism was found in diabetic patients with MI compared to diabetic patients without CAD (27.5% vs. 21.1%, p = 0.04). On the other hand, the 1192G>A (rs2305948) polymorphism was not associated with MI in subjects with type 2 diabetes. Significantly higher VEGF serum levels were found in subjects with the − 604CC genotype compared to those with other (CT + TT) genotypes (73.8 ± 22.1 ng/l vs. 58.1 ± 18.5 ng/l; p < 0.01). Multiple logistic regression analysis adjusted for age, arterial hypertension, LDL cholesterol, HDL cholesterol and hsCRP revealed that carriers of the − 604CC genotype (rs2071559) had a 1.6-fold higher risk for MI (OR = 1.6; 95% CI = 1.1–2.1; p = 0.022).ConclusionThe present study demonstrates that the CC genotype of the KDR − 604T>C polymorphism (rs2071559) is a possible risk factor for MI in Caucasians with T2DM.     

Diabetes nurse case management: Improving glucose control: 10 years of quality improvement follow-up data

The purpose of this retrospective case-control review is to determine the effectiveness of a registered nurse case managers (RNCMs) certified diabetes educator (CDE) quality improvement case management program. RNCMs have a long tradition of providing chronic care intervention, particularly for the high-risk diabetes population with glycosylated hemoglobin (A1C) of 9% or more. However, limited data are available with regard to evaluation of such programs in a Veterans Health Administration population.ResultsA large population (N = 3956) of high-risk veterans with a baseline A1C of 9% or more (mean = 10.6%) was seen by the RNCM's. Paired T-tests of A1C after the last RNCM visit showed a statistically significant A1C reduction (p < 0.001) (mean = 8.5%), after 14–26 months of intervention.ConclusionsRNCMs clinical intervention demonstrated significant A1C reduction (~ 2%). This is an important finding for health care policy makers for planning interventions with respect to long-term management of diabetes mellitus.     

Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial

BackgroundCytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS.MethodsThis study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1 g/day) or a matched placebo for a period of 8 weeks.ResultsOne hundred and seventeen subjects were assigned to either curcumin (n = 59) or placebo (n = 58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 following curcumin supplementation (p < 0.001). In the placebo group, serum levels of TGF-β were decreased (p = 0.003) but those of IL-6 (p = 0.735), TNF-α (p = 0.138) and MCP-1 (p = 0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 in the curcumin versus placebo group (p < 0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines.ConclusionResults of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.     

Relationship between genetic polymorphisms of angiotensin-converting enzyme and methylenetetrahydrofolate reductase as risk factors for type 2 diabetes in Tunisian patients

Background/aimsThe role of methylenetetrahydrofolate reductase (MTHFR) and angiotensin-converting enzyme (ACE) gene polymorphisms as being risk factors for diabetes is still controversial. The aim was to investigate the distribution of ACE and MTHFR genotypes as well as to evaluate the role of plasmatic total homocysteine levels (tHcy) and ACE activity in Tunisian patients with type 2 diabetes mellitus (T2DM).Design and methods115 T2DM patients compared to 116 healthy volunteers.ResultsThe ACE I/D polymorphism was significantly associated with diabetes (p < 0.0001). The DD genotype and D allele were more frequent in patients compared to control group [DD: OR = 4.93; p < 0.0001; 95 % CI: 2.71–8.97; D: OR = 3.08, 95% CI: 2.09–4.51 p < 0.0001]. MTHFR allele and genotype frequencies did not differ between patients and controls. The susceptibility to diabetes in individuals with genotypes DD +vTT was 13.39 and in the individuals with DD + CT was 6.57 times that of the controls. However, individuals with genotypes ID + CC or II + CT have a protective effect against diabetes. The DD and TT genotypes were associated with significantly higher ACE activity and tHcy levels in diabetics.ConclusionOur data suggest that ACE ID polymorphism may act synergistically with MTHFR C677T polymorphism to assess diabetes risk.     

Measuring and improving cardiopulmonary resuscitation quality inside the emergency department

Aim of studyTo evaluate CPR quality during cardiac resuscitation attempts in an urban emergency department (ED) and determine the influence of the combination of scenario-based training, real-time audiovisual feedback (RTAVF), and post-event debriefing on CPR quality.MethodsCPR quality was recorded using an R Series monitor-defibrillator (ZOLL Medical) during the treatment of adult cardiac arrest patients. Phase 1 (P1; 11/01/2010-11/15/2012) was an observation period of CPR quality. Phase 2 (P2; 11/15/2012-11/08/2013) was after a 60-min psychomotor skills CPR training and included RTAVF and post-event debriefing.ResultsA total of 52 cardiac arrest patients were treated in P1 (median age 56 yrs, 63.5% male) and 49 in P2 (age 60 yrs, 83.7% male). Chest compression (CC) depth increased from 46.7 ± 3.8 mm in P1 to 61.6 ± 2.8 mm in P2 (p < 0.001), with the percentage of CC ≥ 51 mm increasing from 30.6% in P1 to 87.4% in P2 (p < 0.001). CC release velocity increased from 314 ± 25 mm/s in P1 to 442 ± 20 mm/s in P2 (p < 0.001). No significant differences were identified in CC fraction (84.3% P1 vs. 88.4% P2, p = 0.1), CC rate (125 ± 3 cpm P1 vs. 125 ± 3 cpm P2, p = 0.7), or pre-shock pause (9.7 s P1 vs. 5.9 s P2, p = 0.5), though CC fraction and pre-shock pause were within guideline recommendations.ConclusionImplementation of the bundle of scenario-based training, real-time audiovisual CPR feedback, and post-event debriefing was associated with improved CPR quality and compliance with CPR guidelines in this urban teaching emergency department.     

Plasma advanced glycation endproduct,methylglyoxal-derived hydroimidazolone is elevated in young,complication-free patients with Type 1 diabetes

ObjectivesElevated advanced glycation endproducts (AGEs) are implicated in diabetic complications. Methylglyoxal-derived hydroimidazolone (MG-H) is one of the most abundant AGEs in vivo. Our objective was to develop a time-saving, specific method to measure free MG-H in plasma and determine its levels in complication-free young individuals with Type 1 diabetes (T1DM). The relationship of plasma free MG-H to hemoglobin A1C (A1C) and plasma methylglyoxal levels was also determined.Design and methodsA solid phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, and free plasma MG-H levels were measured in 40 T1DM patients (DM group), aged 6–21 years, and 11 non-diabetics (ND group), 6–22 years. Methylglyoxal was measured using LC-MS/MS and A1C by a Tosoh G7 high-performance liquid chromatograph.ResultsOur method showed high recovery, sensitivity and short run-time. Plasma free MG-H (nmol/L) was higher (p < 0.001) in the DM group (1318 ± 569; mean ± standard deviation) as compared to the ND group (583 ± 419). Within the DM group, plasma free MG-H did not correlate with plasma methylglyoxal or A1C.ConclusionsOur LC-MS/MS method to measure free MG-H in plasma may be useful for future clinical application. The increased levels of free MG-H observed in individuals with TIDM are not merely the result of short term changes in glucose or methylglyoxal, but may reflect long-term alterations to tissue proteins.     

Predictive value of thrombopath determination in women with infertility and pregnancy complications

BackgroundA condition of maternal thrombophilia, either inherited or acquired, can compromise the success of implantation and foetal survival.MethodsMalfunctions in protein C pathway were evaluated using a novel assay [HemosIL ThromboPath (ThP)] in a case-control study of 172 women with a history of recurrent miscarriage or infertility and 86 age-matched unrelated fertile women.ResultsThrombophilia was ascertained in 13% of the cases. ThP values were lower in women either with or without thrombophilia compared to controls (both p < 0.0001). Abnormal ThP values (below the mean minus 1SD of controls) were found in 62% of cases compared to 12% of controls (p < 0.0001). Non-thrombophilic women who achieved spontaneous pregnancy had higher ThP values compared to those who did not (p < 0.05). Elevated ThP values were an independent predictor for pregnancy (p < 0.01) in women without thrombophilia. A decrease of ThP values was observed during pregnancy progression, which correlated with that of protein S (p < 0.05). Miscarriage or major complications occurred in women in whom ThP percent change was approximately 2-fold higher than that observed in women who achieved successful pregnancy (p < 0.05).ConclusionsThP might represent an efficient assay for screening women with pregnancy complications and might provide prognostic information during pregnancy progression.     

EZ-IO® intraosseous device implementation in German Helicopter Emergency Medical Service

BackgroundIntraosseous access (IO) is a rapid and safe alternative when peripheral venous access is difficult. Our aim was to summarize the first three years experience with the use of a semi-automatic IO device (EZ-IO^®) in German Helicopter Emergency Medical Service (HEMS).MethodsIncluded were all patients during study period (January 2009–December 2011) requiring an IO access performed by HEMS team. Outcome variables were IO rate, IO insertion success rates, site of IO access, type of EZ-IO^® needle set used, strategy of vascular access, procedure related problems and operator's satisfaction.ResultsIO rate was 0.3% (348/120.923). Overall success rate was 99.6% with a first attempt success rate of 85.9%; there was only one failure (0.4%). There were three insertion sites: proximal tibia (87.2%), distal tibia (7.5%) and proximal humerus (5.3%). Within total study group IO was predominantly the second-line strategy (39% vs. 61%, p < 0.001), but in children < 7 years, in trauma cases and in cardiac arrest IO was more often first-line strategy (64% vs. 28%, p < 0.001; 48% vs. 34%, p < 0.032; 50% vs. 29%, p < 0.002 respectively). Patients with IO access were significantly younger (41.7 ± 28.7 vs. 56.5 ± 24.4 years; p < 0.001), more often male (63.2% vs. 57.7%; p = 0.037), included more trauma cases (37.3% vs. 30.0%; p = 0.003) and more often patients with a NACA-Score ≥ 5 rating (77.0% vs. 18.6%; p < 0.001). Patients who required IO access generally presented with more severely compromised vital signs associated with the need for more invasive resuscitation actions such as intubation, chest drains, CPR and defibrillation. In 93% EZ-IO^® needle set handling was rated “good”. Problems were reported in 1.6% (needle dislocation 0.8%, needle bending 0.4% and parafusion 0.4%).ConclusionsThe IO route was generally used in the most critically ill of patients. Our relatively low rate of usage would indicate that this would be compatible with the recommendations of established guidelines. The EZ-IO^® intraosseous device proved feasible with a high success rate in adult and pediatric emergency patients in HEMS.     

Evolution,safety and efficacy of targeted temperature management after pediatric cardiac arrest

BackgroundIt is unknown whether targeted temperature management (TTM) improves survival after pediatric out-of-hospital cardiac arrest (OHCA). The aim of this study was to assess the evolution, safety and efficacy of TTM (32–34 °C) compared to standard temperature management (STM) (<38 °C).MethodsRetrospective, single center cohort study. Patients aged >one day up to 16 years, admitted to a UK Paediatric Intensive Care Unit (PICU) after OHCA (January 2004–December 2010). Primary outcome was survival to hospital discharge; efficacy and safety outcomes included: application of TTM, physiological, hematological and biochemical side effects.ResultsSeventy-three patients were included. Thirty-eight patients (52%) received TTM (32–34 °C). Prior to ILCOR guidance adoption in January 2007, TTM was used infrequently (4/25; 16%). Following adoption, TTM (32–34 °C) use increased significantly (34/48; 71% Chi²; p < 0.0001). TTM (32–34 °C) and STM (<38 °C) groups were similar at baseline. TTM (32–34 °C) was associated with bradycardia and hypotension compared to STM (<38 °C). TTM (32–34 °C) reduced episodes of hyperthermia (>38 °C) in the 1st 24 h; however, excessive hypothermia (<32 °C) and hyperthermia (>38 °C) occurred in both groups up to 72 h, and all patients (n = 11) experiencing temperature <32 °C died. The study was underpowered to determine a difference in hospital survival (34% (TTM (32–34 °C)) versus 23% (STM (<38 °C)); p = 0.284). However, the TTM (32–34 °C) group had a significantly longer PICU length of stay.ConclusionsTTM (32–34 °C) was feasible but associated with bradycardia, hypotension, and increased length of stay in PICU. Temperature <32 °C had a universally grave prognosis. Larger studies are required to assess effect on survival.     

Factors associated with complementary medicine use in pediatric musculoskeletal conditions: Results from a national survey

ObjectivesComplementary and alternative medicine (CAM) use is common in children, but its use has only been investigated in children with musculoskeletal conditions (MSK) to a limited extent. We aimed to characterize factors associated with CAM use in children with MSK conditions.MethodsWithin the 2012 National Health Interview Survey dataset (including its child CAM supplement), we examined factors associated with CAM use in children with MSK conditions and performed an analysis examining the perceived usefulness of CAM therapies for MSK conditions.ResultsOverall, there were 10,218 children in the dataset. 28.0% of children with MSK conditions used CAM, compared to 8.8% of children without MSK conditions. Gender (p = 0.003), region (p = 0.001), race (p = 0.001), parental CAM use (p < 0.001), education (<0.001), and having anxiety, stress or depression (p = 0.030) were correlated with CAM use. Among 90 children who reported on CAM use, 89.7% said that CAM helped some or a great deal for their MSK condition.ConclusionsSeveral factors, particularly parental education and parental CAM use, were associated with CAM use, and self-reported improvement rates were high. Interventional trials are needed to determine the efficacy of specific CAM therapies for treating different MSK conditions in children.     

CYP1A1, CYP1A2 and CYBA gene polymorphisms associated with oxidative stress in COPD

BackgroundThe genetic susceptibility to chronic obstructive pulmonary disease (COPD) depends on detoxification and antioxidant enzymes, which detoxify cigarette smoke reactive components that, otherwise, generate oxidative stress.MethodsIn a case–control study of 346 subjects with and without COPD, we examined the polymorphisms 462Ile/Val, 3801T/C of CYP1A1, ?3860G/A of CYP1A2 and ?930A/G, 242C/T of CYBA individually or in combination and their contribution to oxidative stress markers by measuring malondialdehyde (MDA), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx).ResultsCOPD patients had significantly increased MDA concentration (p < 0.001) and decreased CAT activity, GSH concentration, GPx activity (p ≤ 0.01). The patients were over-represented by the alleles 462Val, 3801C of CYP1A1 and ?930G, 242C of CYBA (p < 0.001, p = 0.003, p = 0.030 and p = 0.031, respectively) and consequently the haplotypes of same alleles i.e. 462Val:3801C, 462Val:3801T and ?930G:242C (p = 0.048, p = 0.016 and p = 0.039, respectively). Similarly, CYP1A1 and CYP1A2 haplotypes, 462Val:3860G and 462Val:3801T:3860G were significantly over-represented (p = 0.001 and p = 0.003), respectively in patients. The same alleles-associated genotype-combinations between genes were more prevalent in patients. Of note, the genotypes, 462Ile/Val+Val/Val, 3801TC+CC of CYP1A1 and ?930AG+GG of CYBA associated with increased MDA concentration (p = 0.018, p = 0.045 and p = 0.017, respectively), decreased CAT activity (p < 0.0001, p = 0.080 and p < 0.0001, respectively) and GSH concentration (p < 0.0001, p = 0.0002 and p = 0.011, respectively) in patients.ConclusionThe identified alleles, its haplotypes and the genotype-combination along with increased oxidative stress, signify the importance in susceptibility to COPD.     

Serum 1,5-anhydroglucitol levels in patients with fulminant type 1 diabetes are lower than those in patients with type 2 diabetes

ObjectivesWe investigated clinical relevance of serum 1,5-anhydroglucitol (1,5-AG) levels in fulminant type 1 diabetes mellitus (FT1DM) patients, because 1,5-AG is known to reflect short term glycemic control.Design and methodsSubjects comprised 7 patients with FT1DM and 32 patients with type 2 diabetes mellitus (T2DM) with HbA1c < 8.5%. All of them have never been treated for diabetes.ResultsHbA_1C showed no significant difference between both groups. On the other hand, serum 1,5-AG levels were significantly lower in the FT1DM patients than in the T2DM patients. Serum 1,5-AG levels were < 5.0 μg/ml in 6 of 7 (86%) FT1DM patients, compared with only 1 of 32 (3%) T2DM patients.ConclusionsSerum 1,5-AG levels were lower in the FT1DM patients than in the T2DM patients. Serum 1,5-AG, but not HbA_1C, reflects short-term exacerbation of glycemia in patients with FT1DM.     

Effects of traditional Korean medicine on anti-Müllerian hormone in patients with diminished ovarian reserve: A retrospective study

ObjectiveThe purpose of the present study is to retrospectively evaluate the effect of traditional Korean medicine (TKM) on ovarian reserve by measuring serum anti-Müllerian hormone (AMH) levels in patients with diminished ovarian reserve (DOR).Study designWe performed a retrospective chart review of patients with DOR who had received TKM for at least 2 months and had undergone serum AMH tests before and after TKM treatment. A total of 22 patients with DOR were included in the study.ResultsThere were no significant differences in AMH levels before and after TKM in all patients (n = 22, p = 0.237). However, when the study population was divided into two age groups (<38 (n = 12) and ≥38 years (n = 10)) to determine whether there was a age-related difference in the effect of TKM with DOR, a significant increase in AMH levels before and after TKM was observed in the age <38 (p < 0.05).ConclusionsTKM may provide an effective option for patients aged <38 years with DOR, but it should be interpreted cautiously as more rigorous research is needed. Further studies in a larger population are needed to confirm these results and to evaluate the effects of improved ovarian reserve on fertility outcomes following TKM in patients with DOR.     

MUC1 expression and its association with other aetiological factors and localization to mitochondria in preneoplastic and neoplastic gastric tissues

BackgroundThe molecular events that underlie the conversion of normal human gastric epithelium into adenocarcinoma are poorly understood. MUC1 overexpression and localization in mitochondria might confer cancer cells with attenuation of stress induced apoptosis. We studied MUC1 expression pattern, interaction with HSP70 and localization in mitochondria in preneoplastic and neoplastic human gastric tissues.MethodsImmunohistochemistry and Western blot were used to study MUC1 expression pattern and localization in mitochondria. Coimmunoprecipitation was used to study MUC1 interaction with HSP70. MUC1 expression was correlated with other causative features including erbB2 expression.ResultsMUC1 was expressed in 75.8% (147/194). MUC1 overexpression was detected in 50.0% (19/38 cases) dysplasia and 58.2% (32/55 cases) adenocarcinoma tissues. MUC1-CT–HSP70 interaction was seen in 71.66% (43/60 cases) and MUC1 localized to mitochondria in 33.33% (5/15) dysplasia samples and in 47.05% (8/17) adenocarcinoma samples. MUC1 expression showed significant association with smoking (χ² = 5.945; p < 0.015), alcohol consumption (χ² = 4.055; p < 0.044) and erbB2 positivity (χ² = 10.75; p < 0.001). MUC1 expression did not show appreciable association with age (χ² = 0.15; p < 0.698), sex (χ² = 0.22; p < 0.640) or Helicobacter pylori infection (χ² = 3.06; p < 0.080).ConclusionsSignificant correlation was found between MUC1 expression and smoking, alcohol and erbB2 expression. MUC1 showed aberrant expression in dysplasia and adenocarcinoma stages. MUC1 cytosolic tail was bound by HSP70 in all the stages but MUC1-CT was found to localize in mitochondria only in dysplasia and adenocarcinoma. MUC1-CT localization to mitochondria in dysplasia and adenocarcinoma might aid in the attenuation of epithelial stress response induced loss of polarity.     

A study on serum advanced glycation end products and its association with oxidative stress and paraoxonase activity in type 2 diabetic patients with vascular complications

ObjectivesEnhanced formation of advanced glycation end products (AGEs) formed secondary to hyperglycemic conditions has been linked to diabetes mellitus (DM) associated complications. We investigated the clinical relevance of estimating AGEs and their relationship with oxidative stress (OS) and paraoxonase (PON1) activity in type 2 DM (T2DM) in relation to development of vascular complications.Design and MethodsSerum AGEs along with PON1 activity, protein carbonyl (PCO), advanced oxidation protein products (AOPP), lipid peroxidation (MDA), and total thiol (T-SH) were determined in 157 T2DM patients (DM without complications n = 57, DM micro-vascular complications n = 53, DM macro-vascular complications n = 47) and 40 healthy controls.ResultsSerum AGE level increased significantly in various study groups in following manner: healthy control < DM without complications < DM-macro < DM-micro. Logistic regression analysis using diabetic complications as dependent variable showed significant association with AGE level and PON1 activity even after adjustment for confounding factors. Receiver-operating-characteristics curve analysis showed that 2-fold increased in glycation and 50% decrease in PON1 activity may lead to development of vascular complications in diabetic subjects. PCO, AOPP and MDA were higher and PON1 activity was lower in T2DM with complications than those without complications. Among diabetic patients AGEs showed significant positive correlation with HbA_1C, MDA, AOPP, and negative correlation with PON1 activity and T-SH.ConclusionHigh serum AGE concentration and low PON1 activity may be considered as additional risk factor for development of vascular complications in T2DM. AGE formation plays significant role in induction of OS in diabetes.