Munetada Oimomi

Glycosylated haemoglobin in renal failure

Dear Sir, De Boer et al. [1] reported that levels of glycosylated haemoglobin [HbA1] were elevated in patients with renal failure. On the other hand, Dandona et al. [2] reported that HbA 1 levels were decreased in patients with renal failure because of the shortened life-span of erythrocytes. In a recent publication in Diabetologia, Graf et al. [3] performed glucose tolerance tests in order to investigate the relationship between glucose tolerance and HbA 1 in renal failure. They found an elevation of HbA 1 levels which did not correlate with the degree of impaired glucose tolerance. We ]xave also investigated whether or not the elevation of HbA 1 values in patients with renal failure was related to impaired glucose tolerance using high-performance liquid chromatography, the microcolumn method, and the thiobarbituric acid colorimetric test [4] for the measurement of t-IbA 1. The high-performance liquid chromatographic quantification of components of the HbA l fraction showed that, in diabetic patients, the increase of HbAlc was mainly due to an increase in the HbAlc fraction (Table 1). In contrast, patients with renal failure showed increases not only in HbA1, but also in the HbAla+b fractions. Thus, the fractional pattern of HbA 1 in patients with renal failure was similar to that seen in normal subjects rather than in diabetic patients. In another study, we have estimated HbA I levels in diabetic patients, in patients with renal failure and in normal subjects using the colorimetric method in which compounds generated from glycosylated haemoglobin on heating under acidic conditions were determined colorimetrically with thiobarbituric acid. These results were compared with data obtained by the microcolumn technique (Fig. 1).

Increased cholesterol concentration in intermediate density lipoprotein fraction of normolipidemic non-insulin-dependent diabetics

There is increasing agreement about the atherogenicity of intermediate density lipoprotein (IDL). In order to determine whether normocholesterolemic diabetics are at a higher risk of atherosclerosis, cholesterol concentrations in three subclasses of triglyceride-rich lipoprotein fraction (Sf 12-400) were examined. Their plasma triglyceride and cholesterol levels were limited to below 150 and 250 mg/dl, respectively. They were divided into 3 groups according to their treatment: insulin injection (group I), sulphonylurea (group S) and diet alone (group D). Age-matched healthy normolipidemic non-obese subjects served as controls (group C). Triglyceride-rich lipoproteins were separated by ultracentrifugation: very low density lipoprotein (VLDL), Sf 60-400; intermediate density lipoprotein (IDL1), Sf 20-60; IDL2; Sf 12-20. Cholesterol concentrations in total plasma, VLDL, IDL2 and high density lipoprotein (HDL) were all identical in every group. A significant increase in cholesterol concentration was found in IDL1 of groups S and D. Low density lipoprotein-cholesterol of group I was also increased. These findings indicate an increased risk factor in normolipidemic diabetics.

Carbamylation of Insulin and Its Biological Activity

A nonspecific binding reaction between cyanic acid formed from urea and protein or peptide is called carbamylation. In the present study, insulin, a peptide hormone, was subjected to carbamylation and the activity of carbamylated insulin was determined. Both immunological and biological activities of insulin changed on carbamylation. The decrease in biological activity in respect to glucose oxidation of fat cells or receptor-binding capacity of rat hepatocytes was greater than that in immunological activity.

Glycation of cataractous lens in non-diabetic senile subjects and in diabetic patients.

Early- and advanced-stage products in the Maillard reaction, glycation, were measured in patients with diabetic or senile cataracts. Early-stage products were measured by means of furosine, which is an acid-hydrolysis product derived from fructose-lysine. Advanced-stage products were measured by fluorometry using high-performance liquid chromatography. Furosine levels were high (listed in descending order) in capsule, cortex and nucleus in both diabetic and senile cataracts. The advanced-stage products were also high (listed in descending order) in nucleus, cortex and capsule in both diabetic and senile cataracts. These results suggest that advanced-stage products might accumulate in larger amounts in the nucleus and cortex than in the capsule, resulting in the formation of cataracts. The study also revealed that the Maillard reaction plays an important role in causing not only diabetic cataracts but also senile cataracts.

Creatine phosphokinase isozymes of human heart muscle and skeletal muscle

Abstract Creatine phosphokinase (CPK) of human cardiac muscle and skeletal muscle was fractionated by column chromatography on DEAE-Sephadex A-So. The intermediate type enzyme of the cardiac muscle was located in the β-globulin fraction in difference to the intermediate type enzyme of skeletal muscle, which was found in the α2-globulin fraction. Ontogenetic change of cardiac CPK isozymes in normal human tissue and CPK patterns of clinical cases including muscular dystrophy are reported.

An outbreak of fulminant hepatitis B in immunocompromised hemodialysis patients

BackgroundWe aimed to clarify the pathogenesis of an outbreak of fulminant hepatitis B in hemodialysis (HD) patients whose compromised cell-mediated immunity in turn contributed to chronic hepatitis B virus (HBV) carriage.MethodsFive consecutive adult HD patients with acute hepatitis B were evaluated. Viral genotype, mutations, and HBV-DNA levels were studied in relation to viral clearance, liver disease severity, and liver histology by immunostaining.ResultsAll five patients had hepatitis B surface antigen (HBsAg) genotype C, a G-to-A stop codon mutation at nucleotide (nt) 1896 in the precore region, an A-to-T mutation at nt 1762 and an G-to-A mutation at nt 1764 in the basal core promoter. The possible index patient, who suffered from liver cirrhosis, had HBsAg genotype C, anti-hepatitis B envelope (HBe), and these mutations. The level of HBV-DNA declined by about 10 percent per week and no difference in viral kinetics between the patients who died and the survivor was found, irrespective of therapies. The amount of liver cell apoptosis, as assessed by single-stranded DNA, was scarce. The risk of fulminant hepatic failure did not correlate with the preexistent liver histopathological changes. Acute HBV superinfection was associated with hepatitis C virus (HCV) elimination and increased mortality.ConclusionsThis outbreak of fulminant hepatitis B suggests that HD patients can foster highly virulent HBV strains (possibly owing to their compromised immune responses), which may place others at risk of severe, life-threatening acute liver damage and at increased risk of mortality if chronic carriers of HCV should be infected.

Carbamylation of hemoglobin in renal failure and clinical aspects.

It was revealed that in renal failure hemoglobin A1 (HbA1) was formed by the binding of substances other than glucose to Hb. It was elucidated that the formation of HbA1 increased in urea-added medium and further increased in media containing urea either stored at 37 degrees C for 1 week or heated at 100 degrees C for five minutes. The increment of HbA1 was proportional to the amount of cyanic acid produced by the treatment of the medium after the addition of urea. We found that there was the best correlation between the HbA1 level and the BUN level of 1 to 2 weeks before. Therefore, it appeared that HbA1 could be an indicator of the state of renal failure of 1 to 2 weeks earlier in patients with renal failure without impaired glucose tolerance, especially in patients on hemodialysis.

Acceleration of Fructose Mediated Collagen Glycation

The effect of fructose on the formation of advanced Maillard reaction products which show fluorescence and have crosslinking was investigated. Type I collagen was added to various concentrations of glucose and fructose which were then incubated at 37°C for 4 weeks. The level of furosine and the fluorescence intensity both increased in direct proportion to glucose and fructose levels and to the duration of incubation. Incubation with fructose produced less furosine but more intense fluorescence than incubation with glucose. Furthermore, collagen was significantly less soluble after incubation with fructose than after incubation with glucose. These results suggest that fructose in the polyol pathway plays an important role in the formation of advanced Maillard products.

Purification of α-ketoaldehyde dehydrogenase from the human liver and its possible significance in the control of glycation

Alfa-ketoaldehyde dehydrogenase, which was extracted and purified from human livers, may act on carbonyl compounds, such as 3-deoxyglucosone, and be involved in the control of glycation (Maillard reaction) in the body.

Increased fructose-lysine of hair protein in diabetic patients

SummaryFructose-lysine, which is formed by binding glucose to lysine, is degraded on acid hydrolysis into furosine. Furosine was determined by high-performance liquid chromatography according to the method of Schleicher et al. Furosine values were significantly higher in diabetic patients than in healthy subjects, and significantly correlated with haemoglobin A1 (HbA1) values. These results suggest that furosine, like HbA1, may become an indicator of long-term blood glucose control in diabetic patients and be useful in investigating diabetic complications on the level of tissue.