Comparison of HbA1c and oral glucose tolerance test for diagnosis of diabetes in patients with coronary artery disease

Background

Measurement of glycated hemoglobin A1c (HbA1c) to diagnose diabetes mellitus (DM-2) is recommended by several expert groups. DM-2 occurs very frequently among patients with coronary artery disease (CAD). Therefore, we aimed to investigate the diagnostic strengths of HbA1c and oral glucose tolerance test (OGTT) in detecting latent glucometabolic disturbances among patients with CAD.

Materials and methods

One hundred ninety-nine consecutive patients admitted with CAD were included in this observational study. Fasting plasma glucose as well as HbA1c measurement was performed in all study participants and those without preexisting DM-2 underwent an OGTT.

Results

Patients were subdivided according to their medical history into those with previous DM-2 (n?=?37). The remaining 162 patients underwent OGTT, which revealed 39 patients with diabetes (DM-_OGTT), 35 with impaired glucose tolerance (IGT), 20 with impaired fasting glucose (IFG) and 68 with normal glucose tolerance (NGT). Using HbA1c resulted in 6.8% DM and 45.6% at risk (HbA1c 5.7–6.4%) diagnosis. OGTT identified 24.1% DM (p?=?0.002 compared with HbA1c) and 21.6% IGT patients. Among those with intermediate HbA1c (5.7–6.4%) 26.5% patients were NGT and only 30.9% displayed DM-2 by use of OGTT. Among patients with HbA1c of <5.7%, 44% (n?=?31) of patients had disturbed glucose metabolism. Using receiver-operating curve HbA1c cutoff with the highest sensitivity and specificity was found to be 5.8%.

Discussion

There is a large discordance between OGTT and HbA1c in terms of detecting latent DM-2 in patients with CAD. Measurement of HbA1c could result in lower propensity of DM-2 diagnosis.     

The effect of NeuroAiD™ (MLC601) on cerebral blood flow velocity in subjects' post brain infarct in the middle cerebral artery territory

Background

Stroke is the third common cause of mortality and the most common cause of morbidity in adults. MLC601 (NeuroAiD™) is a treatment indicated for post stroke recovery. An increase of impaired cerebral blood flow may be an important parameter for recovery processes. The aim of this study was to investigate the effect of MLC601 on cerebral blood flow velocity as an indirect evidence of cerebral blood flow increase in post stroke subjects.

Methods

This is a double-blinded, placebo controlled, randomized study of 80 subjects included within a week of stroke onset. All subjects were given either MLC601 or placebo, 4 capsules, 3 times a day for 3 months. Cerebral blood flow within the middle cerebral artery, with blood flow velocity measured by transcranial Doppler (TCD), and Barthel index was assessed at baseline and at 3 months.

Results

The mean change in cerebral blood flow velocity in the MLC601 treatment group (15.9) was significantly increased (p = 0.009) compared to the placebo group (9.6). Subjects in the treatment group also showed a significant difference in the mean rank of modified ranking scale (p < 0.001) and mean change of the Barthel Index: 36 vs. 29 in the placebo group (p < 0.001).

Conclusion

This is the first study suggesting that treatment with MLC601 may increase cerebral blood flow in stroke subjects. This may be mediated by an effect on stimulating microcirculation, an important process contributing to neuroplasticity in the central nervous system. This effect on cerebral blood flow may be associated with improvement in measures of functional recovery.     

Retinoic acid can induce markers of endocrine transdifferentiation in pancreatic ductal adenocarcinoma: preliminary observations from an in vitro cell line model

BACKGROUND AND HYPOTHESIS: The pancreatic ductal adenocarcinoma (HPAF) cells have a multipotent stem cell potential. It was hypothesised that all-trans-retinoic acid (atRA) can induce transdifferentiation of these cells into cells with an endocrine phenotype. MATERIAL AND METHODS: To explore this hypothesis, an in vitro system of cells was established. Some cells were treated with atRA at concentrations of 100 nmol/l (non-apoptosis-inducing) and 5 micromol/l (apoptosis-inducing) and harvested. Cells were examined for cell cycle kinetics, apoptosis (terminal deoxynucleotidyl transferase assay and p53 protein expression) and immunomorphological features of redifferentiation (MUC1 and DUPAN-2) and endocrine transdifferentiation (insulin, somatostatin, glucagon, neurone-specific enolase) by using immunoperoxidase staining methods. Levels of insulin, transforming growth factor (TGF) beta2, TGFalpha and epidermal growth factor receptor (EGFR) were measured by enzyme-linked immunosorbent assay (ELISA). The vehicle-treated cells served as a control group. RESULTS: When compared with untreated cells, cells treated with 100 nmol/l and 5 micromol/l atRA were observed to show (1) decreased proliferative activity (cpm) as indicated by decreased incorporation of thymidine labelled with hydrogen-3; (2) cell cycle arrest; (3) increased apoptotic activity associated with p53 protein overexpression; (4) upregulated expression of the transdifferentiation and redifferentiation markers; (5) morphological changes indicative of transdifferentiation (increased cell size and appearance of dendrites); (6) decreased production of EGFR; (7) upregulation of TGFalpha and TGFbeta2; and (8) increase in basal and glucose-induced insulin secretion. CONCLUSIONS: Functional endocrine transdifferentiation can be induced in HPAF lines by atRA. Further investigations are mandated to explore the underlying mechanisms of this transdifferentiation and to explore its in vivo extrapolation.     

Structural study on immunoglobulin G solution after pasteurization with and without stabilizer

summary .  Pasteurization was investigated as a method of inactivating virus during the preparation of immunoglobulin for intravenous use. The effect of pH, protein concentration and the presence of protein stabilizers on the structure of immunoglobulin G (IgG) molecules during pasteurization was investigated using an immunoglobulin solution derived from a Cohn's fraction II preparation. Changes in the secondary and tertiary structure of IgG molecules as well as the degree of polymerization of protein were investigated using spectrophotometry, circular dichroism and size exclusion chromatography. Only slight changes in secondary and tertiary structure were observed after pasteurization in a 10 g L⁻¹ immunoglobulin solution at pH 4·5 and 5·5 in the absence of stabilizer and in a 50 g L⁻¹ immunoglobulin solution at pH 5·5 in the presence of glycine and sucrose or sorbitol. Concentrations of immunoglobulin solution below 20 g L⁻¹ were not denatured when pasteurized at pH 4·5 in the absence of stabilizers. High concentrations of immunoglobulin solution required stabilizers such as glycine and sorbitol or sucrose to prevent or reduce denaturation during pasteurization.     

High levels of platelet-monocyte aggregates after valve replacement for aortic stenosis: relation to soluble P-selectin and P-selectin glycoprotein ligand-1 genes

Background

Calcific aortic valve stenosis is linked to atherosclerosis. The latter is associated with increased levels of platelets adhering to monocytes (PMA).

Objective

The hemodynamic impairment in symptomatic aortic valve stenosis can be abated by valve replacement. We investigated the effect of valve replacement on PMA and receptor-ligand axis P-selectin - P-selectin glycoprotein ligand-1 (PSGL-1) in severe aortic valve stenosis.

Patients and Methods

PMA, plasma P-selectin (sP-selectin) and polymorphisms within the coding region for PSGL-1 (SELPLG) were determined in 42 patients with severe aortic valve stenosis before and 4 to 8 months after valve replacement. Ten patients suffered from significant coronary artery disease and received also a coronary artery bypass graft. Thirty-four patients received a bioprosthetic valve and 8 patients who were < 65 years old received a mechanical valve.

Results

Before the intervention, PMA levels were significantly higher in patients with aortic valve stenosis than in two control cohorts, namely healthy indviduals and 88 age- and sex-matched patients with severe atherosclerosis, but without aortic valve stenosis (p < 0.001). PMA decreased after surgery, but normalized in only 3 patients, while further increases were noted in 11 patients. sP-selectin was elevated in 3 and 4 patients before and after valve replacement, respectively. sP-selectin increased significantly after surgery, but remained within the normal range. There was no correlation between changes of PMA and sP-selectin or any of the polymorphisms within SELPLG.

Conclusions

Exceedingly high PMA in aortic stenosis are independent of SELPLG polymorphisms, and largely of the hemodynamic compromise caused by the stenotic valve.     

Characterisation of<Emphasis Type="Italic"> potato virus Y</Emphasis> isolates from Iran

A survey of Potato virus Y (PVY) was conducted in cultivated fields in six Iranian provinces between January 2005 to July 2007. Two hundred samples from potato and tomato were collected and analyzed by enzyme-linked immunosorbent assay (ELISA) for potyviruses. Almost one fourth of the samples were found to be infected by PVY. Analysis of these PVY-positive samples using three monoclonal antibodies (MAbs) facilitating the simultaneous detection of three main strains namely the ordinary (PVY^O), strain (PVY^N) and C (PVY^C) strains. However, the fourth strain (PVY^NTN) and some others recombinant isolates were also identified by molecular methods. Host range and symptoms analysis using sap inoculation of four different strains of PVY onto a range of plants revealed that the four strains showed biological properties that seemed to be consistent with their molecular grouping. Fourteen isolates of PVY were chosen based on the host and geographical location, primer specificity and serology for further biological and molecular characterisation. The coat protein (CP) and P1 genes and 3′-non-translated region (3′NTR) from 14 representative isolates were sequenced and analysed with the sequences available in GenBank. Composite analysis of the P1, CP and 3′-UTR sequences with all full genome sequences of PVY revealed that there are three potential strains of PVY in Iran, PVY^O, PVY^N-W and PVY^NTN. Isolate KER.SA_N was the most divergent of all the 14 isolates reacted with PVY^N specific MAbs but grouped with PVY^O strains in maximum likelihood phylogentic analysis. The PVY^NTN isolates from Iran more closely related to the European than North American PVY^NTN isolates.     

Osteonecrosis of the jaw in the course of multiple myeloma treatment and bisphosphonate administration

The osteonecrosis of jaws is a phenomena newly described in the connection with bisphosphonate therapy. We describe a case of a 41 years old man with multiple myeloma, who developed the osteonecrosis of jaw in the course of antimyeloma therapy. The men had tooth pain from the beginning of the chemotherapy, but the extraction was performed till one month before high dose chemotherapy with peripheral stem cell transplantations, when the conservative therapy was find unsatisfactory. Bisphosphonate were administered from the beginning of the chemotherapy, the bisphosphonate therapy was started with clodronate and later changed to zoledronate. One year from the tooth extraction the wound did not heeled and therefore resection of the necrotic bone was performed. The pain in the jaw was diminished, but the wound is not completely heeled. The administration of bisphosphonate was stopped after the diagnosis osteonecrosis of the jaws.     

Novel aspartic-based bio-MOF adsorbent for effective anionic dye decontamination from polluted water

In this study, a cost-effective powdered Zn l-aspartic acid bio-metal organic framework (Zn l-Asp bio-MOF) was reported as an efficient adsorbent for Direct Red 81 (DR-81) as an anionic organic dye. The prepared bio-MOF was characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), field emission transmission electron microscopy (FETEM), surface area analysis (BET), and thermal gravimetrical analysis (TGA). The resulting bio-MOF has a large surface area (180.43 m² g⁻¹) and large mesopore volume (0.144 cm³ g⁻¹), as well as good chemical inertness and mechanical stability. The optimum dosage from the Zn l-Asp bio-MOF was 1.0 g L⁻¹ at pH = 7 for 95.3% adsorption of 10 ppm DR-81 after 45 min. Thermodynamic analysis results demonstrated that the decontamination processes were done with spontaneous, thermodynamically, and exothermic nature onto the fabricated bio-MOF. Kinetic parameters were well-fitted with pseudo-second-order kinetics, and the adsorption process was described by the Freundlich isotherm. The adsorption data proved that Zn l-Asp bio-MOF is an effective adsorbent for DR-81 from aqueous solutions with high stability and recycling ability for eight cycles, as well as the easy regeneration of the sorbent.

In this study, a cost-effective powdered Zn l-aspartic acid bio-metal organic framework (Zn l-Asp bio-MOF) was reported as an efficient adsorbent for Direct Red 81 (DR-81) as an anionic organic dye.