CARDIOPROTECTIVE EFFECT OF l-GLUTAMATE IN OBESE TYPE 2 DIABETIC ZUCKER FATTY RATS

• 1 Because diabetic hearts have an increased threshold for cardioprotection by ischaemic preconditioning (IPC), we hypothesized that protection by l ‐glutamate during reperfusion is restricted in Type 2 diabetic hearts. Previously, we found that l ‐glutamate‐mediated postischaemic cardioprotection mimics IPC.
• 2 Rat hearts were studied in a Langendorff preparation perfused with Krebs’–Henseleit solution and subjected to 40 min global no‐flow ischaemia, followed by 120 min reperfusion. l ‐Glutamate (0, 15 and 30 mmol/L) was added to the perfusate during reperfusion of hearts from non‐diabetic (Wistar‐Kyoto) and diabetic (Zucker diabetic fatty (ZDF)) rats, studied at 16 weeks of age. The infarct size (IS)/area‐at‐risk (AAR) ratio was the primary end‐point. Expression of l ‐glutamate excitatory amino acid transporter (EAAT) 1 (mitochondrial) and EAAT3 (sarcolemmal) was determined by quantitative polymerase chain reaction and immunoblotting.
• 3 The ISS/AAR ratio did not differ between control hearts from Wistar‐Kyoto and ZDF rats (0.52 ± 0.03 and 0.51 ± 0.04, respectively; P = 0.90). l ‐Glutamate (15 mmol/L) significantly reduced the IS/AAR ratio in non‐diabetic hearts, but not in diabetic hearts, compared with their respective controls. The higher concentration of l ‐glutamate (30 mmol/L) reduced infarct size in diabetic hearts to the same degree as in non‐diabetic hearts (IS/AAR 0.35 ± 0.03 (P = 0.002) and 0.34 ± 0.03 (P = 0.004), respectively). The mitochondrial l ‐glutamate transporter EAAT1 was downregulated in hearts from ZDF rats at both the mRNA and protein levels (P < 0.0005 and P < 0.0001, respectively). However, there was no change in EAAT3 expression at the protein level. Myocardial l ‐glutamate content was increased by 43% in diabetic hearts (P < 0.0001).
• 4 Hearts from obese diabetic rats have an elevated threshold for metabolic postischaemic cardioprotection by l ‐glutamate. These findings may reflect underlying mechanisms of inherent resistance against additional cardioprotection in the diabetic heart.

     

Comparison of vaginal and sublingual misoprostol for second trimester abortion: randomized controlled equivalence trial

BACKGROUND: To identify an effective misoprostol-only regimen for the terminationof second trimester pregnancy, we compared sublingual and vaginaladministration of multiple doses of misoprostol in a randomized,placebo-controlled equivalence trial. METHODS: Six hundred and eighty-one healthy pregnant women requestingmedical abortion at 13–20 weeks' gestation were randomlyassigned within 11 gynaecological centres in seven countriesinto two treatment groups: 400 µg of misoprostol administeredeither sublingually or vaginally every 3 h up to five doses,followed by sublingual administration of 400 µg misoprostolevery 3 h up to five doses if abortion had not occurred at 24h after the start of treatment. We chose 10% as the margin ofequivalence. The primary end-point was the efficacy of the treatmentsto terminate pregnancy in 24 h. Successful abortion within 48h was also considered as an outcome along with the induction-to-abortion-interval,side effects and women's perceptions on these treatments. RESULTS: At 24 h, the success (complete or incomplete abortion) ratewas 85.9% in the vaginal administration group and 79.8% in thesublingual group (difference: 6.1%, 95% CI: 0.5 to 11.8). Thus,equivalence could not be concluded overall; the difference,however, was driven by the nulliparous women, among whom vaginaladministration was clearly superior to sublingual administration(87.3% versus 68.5%), whereas no significant difference wasobserved between vaginal and sublingual treatments among parouswomen (84.7% versus 88.5%). The rates of side effects were similarin both groups except for fever, which was more common in thevaginal group. About 70% of women in both groups preferred sublingualadministration. CONCLUSIONS: Equivalence between vaginal and sublingual administration couldnot be demonstrated overall. Vaginal administration showed ahigher effectiveness than sublingual administration in terminatingsecond trimester pregnancies, but this result was mainly drivenby nulliparous women. Fever was more prevalent with vaginaladministration. Registered with International Standard RandomizedControlled Trial number ISRCTN72965671 [controlled-trials.com] .     

DNA methylation changes following 5-azacitidine treatment in patients with myelodysplastic syndrome

DNA methyltransferase inhibitor, 5-azacitidine (AC) is effective in myelodysplastic syndromes (MDS) and can induce re-expression in cancer. We analyzed the methylation of 25 tumor suppressor genes in AC-treated MDS. Hypermethylation of CDKN2B, FHIT, ESR1, and IGSF4 gene was detected in 9/44 patients. In concordance with the clinical response, a lack of or decreased methylation in 4 patients with hematologic improvements and persistent methylation in 4 others with no response was observed. The mRNA expression of CDKN2B, IGSF4, and ESR1 was significantly reduced in MDS. Our results suggest that methylation changes contribute to disease pathogenesis and may serve as marker to monitor the efficacy of treatments.     

First report on clinical features of Mycoplasma pneumoniae infections in Vietnamese children

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) in children, but there has been no clinical report on M. pneumoniae infections in Vietnamese children. We investigated the clinical features of M. pneumoniae infection when the pathogen was detected in the respiratory tract in hospitalized children aged 1-15 years due to lower respiratory tract infections or CAP in Vietnamese children. Throat swabs from 47 patients (18.6%) of 252 patients with a clinical diagnosis of CAP were PCR positive (male, 34; female, 13), and 21 throat swabs (8.3%) showed culture positive for M. pneumoniae. The M. pneumoniae pathogen could be detected by PCR and/or culture in 52 patients (male, 36; female, 16). The major clinical signs in the 52 patients were fever (>38 degrees C) in 100%, pharyngitis in 100%, tachypnea in 94%, dry cough in 86.5%, and rough breathing in 83% of patients. The average term of illness prior to hospitalization was 7.5+/-4.1 days, and the average number of hospitalized days was 7.9+/-3.5 days. Beta-lactam group antibiotics, which were ineffective against M. pneumoniae infection, were used in 37 cases (71%).     

Choroidal metastasis revealing pulmonary adenocarcinoma

Lung cancer is the first cause of choroidal metastasis in man. Generally, its discovery is made at end-stage of the disease. It can be uncommonly the presenting sign as in our case. We report a case of a 28-year-old patient with no prior medical history. He presented with visual decrease and metamorphopsia that lead to the diagnosis of a metastatic adenocarcinoma of the lung (bone, liver, choroid, nodles). Chemotherapy permitted to improve visual acuity, in parallel with disappearance of choroidal metatasis. Discovery of choroidal tumor should evoke in first line metastasis. Chemotherapy can improve visual acuity and the quality of life.     

Assessment of the risk factors associated with type 2 diabetes and prediabetes mellitus: A national survey in Vietnam

This study aims to estimating the prevalence of type 2 diabetes and prediabetes among adult from 30 to 69 years old and assess the association of risk factor with the conditions. A total of 5244 aged 30 to 69 years old were participated in this cross-sectional study, using nationally representative sampling frame. All participants were taking blood sample to measure fasting blood glucose level and 2-hour postload oral glucose tolerance test by National Hospital of Endocrinology, Vietnam. Multinomial logistic regressions with baseline-category logit models were conducted to identify factors associated with diabetes and prediabetes among respondents. The prediabetes prevalence was in 17.9% and diabetes in 7.3%. Patients who were male (reference group vs female OR = 0.79; 95% CI: 0.64, 0.97), in the 50 to 59 years old group (OR = 1.60; 95% CI: 1.28, 2.00), have hypertension and WHR risk have higher prevalence to have prediabetes (OR = 1.31; 95% CI: 1.12, 1.53; OR = 1.37; 95% CI: 1.11, 1.70, respectively). Male patients (reference group vs female OR = 0.62; 95% CI: 0.45, 0.84), patients who were in 40 to 49; 50 to 59; 60 to 69 years old, those who were housewife (OR = 2.17; 95% CI: 1.43, 3.28; OR = 2.85; 95% CI: 1.91, 4.27; OR = 3.12; 95% CI: 2.08, 4.69; OR = 1.71; 95% CI: 1.22, 2.40, respectively). Diabetes have significant associated with participants have hypertension (OR = 1.19; 95% CI: 1.72, 2.70). The common factor directly related to prediabetes and diabetes in both genders is age. Other factors directly associated with prediabetes and diabetes include BMI, WHR, hypertension, educational level, and job.