Glycosylated hemoglobins and diabetes mellitus.

Glycosylated hemoglobins result from post-translational changes in the hemoglobin molecule, and their levels correlate well with glycemic levels over the previous six to 10 weeks. Their use as an aid in monitoring diabetic control appears to be well established, but their value in predicting complications of diabetes and in diagnosing milder forms of diabetes is as yet unknown. Of the numerous methods available for the analysis of glycosylated hemoglobins, none has been evaluated extensively in a routine laboratory setting. However, liquid chromatography, isoelectric focusing, and radioimmunoassay techniques all give adequate results. For the purposes of monitoring long term diabetic control, assay of the fast hemoglobin fraction (AIa+b+c) appears adequate. However, for investigative purposes, when optimal sensitivity may be required, specific measurement of hemoglobin AIc is recommended.     

Bone marrow lipofuscin

Lipofuscins are commonly present in the macrophages of the marrow. In unstained preparations they may be confused with haemosiderin, but they are readily distinguished by fluorescence microscopy.In contrast to the belief that lipofuscins are a manifestation of senility, no age dependence has been demonstrated.Exceptionally large amounts have been found in illnesses accompanied by fever and leucocytosis, in keeping with the concept of their formation from insoluble remains of ingested cell fragments. It is probable that the ;sea-blue histiocytes', described in the literature, are macrophages laden with strikingly uniform granules of lipofuscin.     

Reversibility of lipofuscin accumulation caused by protein malnutrition in the motor cortex of squirrel monkeys, Saimiri scireus.

Lipofuscin pigment has been demonstrated histochemically in the motor cortex by the use of several histochemical and cytochemical methods in the healthy (maintained on a diet with 25% protein content) and protein malnourished (maintained on a diet with 2% protein content) adult animals. 4 animals in the latter category were rehabilitated over a period of 11 months and various histochemical techniques were repeated on the motor cortex of these animals. The healthy animals showed a somewhat uniform distribution of lipofuscin pigment in the neuronal perikarya with the perineuronal glia showing only slight occurrence of pigment bodies. The malnourished animals exhibited a significantly larger number of lipofuscin bodies in the neuronal as well as glial perikarya. The neurons, especially, showed aggregations of lipofuscin bodies characterized by a large increase in the activity of acid phosphatase and simple esterases. The rehabilitated animals, however, showed a decrease of lipofuscin pigment in the neuronal perikarya with a concomitant loss of lysosomal enzymes, while a significant increase of these bodies was observed in the perineuronal glial cells. It is evident that the formation of lipofuscin pigment gets accelerated under the extrinsic influence of dietary protein deprivation in the adult animals, but the process is reversed at least to some extent by halting the dietary deficiency or its correction by rehabilitation. The perineuronal glial cells appear to play a significant role in the removal of lipofuscin bodies from the neuronal perikarya. The significance of these observations has been discussed.     

Portal lymphadenopathy associated with lipofuscin in chronic cholestatic liver disease.

To determine whether portal lymphadenopathy in primary biliary cirrhosis is caused by deposition of lipofuscin pigment in sinus histiocytes and to compare primary biliary cirrhosis with other liver diseases a retrospective study on a consecutive series of 169 livers obtained at transplantation was carried out. There were grouped into eight diagnostic categories: primary biliary cirrhosis (n = 51), primary sclerosing cholangitis (n = 10), extrahepatic biliary atresia (n = 6), chronic rejection (n = 9), cirrhosis (other causes) (n = 38), primary liver neoplasia (n = 21), acute liver disease (n = 20), and retransplantation (other) (n = 14). Lymph nodes were present in 66 specimens. Fifty of these contained granules of lipofuscin pigment. The highest incidence of lymph node enlargement and the largest amounts of pigment were present in cases of primary biliary cirrhosis. A similar pattern of lymph node enlargement was also commonly observed in other chronic cholestatic conditions (primary sclerosing cholangitis, biliary atresia, chronic rejection). Much less pigment was seen in nodes draining livers with non-cholestatic cirrhosis or primary tumours. Nodes were not found in acute liver disease. It is concluded that portal lymphadenopathy associated with lipofuscin is a common finding in various chronic cholestatic liver diseases. The pathogenesis of this lesion is uncertain. Most cases are asymptomatic with enlarged nodes which may be detected only at laperotomy or necropsy and may be wrongly attributed to neoplastic disease. Diagnostically, the finding of large amounts of lipofuscin in enlarged portal lymph nodes is a good indicator of underlying chronic cholestatic liver disease.     

Glycosylated haemoglobin: measurement and clinical use.

The discovery, biochemistry, laboratory determination, and clinical application of glycosylated haemoglobins are reviewed. Sources of error are discussed in detail. No single assay method is suitable for all purposes, and in the foreseeable future generally acceptable standards and reference ranges are unlikely to be agreed. Each laboratory must establish its own. Nevertheless, the development of glycosylated haemoglobin assays is an important advance. They offer the best available means of assessing diabetic control.     

糖化血红蛋白联合糖化清蛋白测定在妊娠期糖尿病筛查中的应用价值

目的 探讨糖化血红蛋白(HbA1c)联合糖化清蛋白(GA)测定在妊娠期糖尿病筛查中的应用价值.方法 对2015年3月至2016年3月在荆州市中心医院产科做产前检查的GDM孕妇(GDM组)和健康妊娠孕妇(对照组),进行外周血HbA1c、GA检测并分析两组受试者上述指标的差异.结果 GDM组HbA1c、GA阳性检出率均高于对照组,差异具有显著统计学意义(均P＜0.01);且GDM组中HbA1c与GA呈显著性正相关(r=0.958,P＜0.01).结论 HbA1c联合GA检测有助于妊娠期糖尿病的临床诊断和治疗,具有较高的应用价值.     

Combined staining of acidophilic inclusion bodies and lipofuscin granules.

Gomori's trichrome solution is shown to stain intracytoplasmic acidophilic granules that occur in some neuronal types of the human brain. Since nerve cells in the adult human brain can be classified on account of their characteristic pattern of lipofuscin pigmentation, a combined staining method is described for the demonstration of both lipofuscin granules and intracytoplasmic acidophilic granules. Paraffin sections are stained with aldehyde fuchsin and Gomori's trichrome solution. In this manner, the red acidophilic granules are in sharp contrast to the lipofuscin deposits stained in a bluish shade. Due to this staining procedure it is now possible to classify neurons revealing acidophilic granules as well as to determine their exact topographical localization.     

Glycosylated haemoglobin in chronic renal failure and after renal transplantation.

Haemoglobin A1 (HbA1) was determined by ion-exchange chromatography in 37 normoglycaemic patients with chronic renal failure (CRF) and 26 with successful renal transplants. Blood glucose concentrations in patients with CRF were similar to those in controls, and there was a significant correlation between fasting blood glucose concentration and HbA1 in these groups. HbA1 in patients with CRF was, however, significantly lower than that in control subjects. Concentrations of HbA1 in patients on haemodialysis, peritoneal dialysis, and those with steady state CRF prior to dialysis were not significantly different from each other. Whereas patients with successful renal transplants of greater than 3 months' duration had HbA1 concentrations indistinguishable from controls, HbA1 in patients with transplants of shorter duration were significantly lower. These observations are suggestive of a shortened erythrocyte survival in CRF per se. Furthermore, these results indicate: (a) the inadequacy of HbA1 in monitoring the quality of diabetic control in patients with CRF, and (b) the absence of a specific effect of dialysis on HbA1, and the restoration to normal HbA1 after successful renal transplantation.     

Accumulation of cardiac lipofuscin in mammals: correlation between sexual maturation and the first appearance of lipofuscin

Accumulation of lipofuscin is an important phenomenon of the cellular aging process. The first appearance of cardiac lipofuscin showed a good correlation with sexual maturation, which was correlated with maximum life-span of mammals. Large metabolic changes occurred at sexual maturation. From these results, it is suggested that sexual maturation of mammals is the initiation period of the aging process. Correlation between sexual maturation and longevity was re-evaluated using many mammals. Domestic and laboratory animals showed an earlier sexual maturation than other mammals, including rodents.     

Prevention of lipofuscin development in neurons by anti-oxidants

Summary It was documented that ageing is associated with a progressive and highly significant proliferation of the total number of light microscopically visible lipofuscin granules in the grey substance of sections of the cervical spinal cord of Balb/c mice. The mean total numbers (±standard errors) of lipofuscin granules in standard sections of the glutaraldehyde-osmium fixed, epon embedded spinal cords that were examined with a phase contrast light microscope in 1 week, 1 month, 8 months and 18 months old mice were 0, 269±56, 1101±82 and 2464±318, respectively. The population densities of multiglobular lipofuscin units as seen with the electron microscope in random spinal cord neurons of the same 4 age groups corresponded well with the above quantitative, light microscopic data.Continuous treatment for 8 months with either the natural anti-oxidant Vitamin E (-tocopherol) at 40 mg/mouse/week or the synthetic anti-oxidant butylated hydroxytoluene at about 100 mg/mouse/week diminished significantly the proliferation of lipofuscin granules in spinal cord neurons that developed during that period of ageing. No toxicity of any sort was caused by these two treatments.These results provide support for the peroxide theory of lipofuscin biogenesis and encourage further exploration of the possibilities of obtaining greater anti-lipofuscin effects with less molecular bulk of anti-oxidants.Supported by funds from The Louisiana State University School of Medicine in Shreveport     

Phagocytosis and lipofuscin accumulation in lymph node macrophages

Lipofuscin is considered to be undigestible material present in secondary lysosomes. During histological and electron microscopical studies lipofuscin was observed in macrophages in popliteal lymph nodes in 3-6 month-old-male Wistar rats after occlusion of the afferent lymph flow to the lymph node. No pathological alterations were found in the lymph node after the operation. However, the number of macrophages was severely reduced. Simultaneously the number of secondary lysosomes increased in the remaining macrophages reaching a plateau 4 weeks after operation. At this time three quarters of the residual bodies already contained lipofuscin granules. In the following weeks almost all macrophages showed lipofuscin in increasing amounts. Macrophages in normal contralateral lymph nodes of the same rats rarely contained lipofuscin. The increased phagocytosis of the remaining macrophages thus preceded the appearance of lipofuscin. We suggest that lipofuscin results from an inadequate intralysosomal digestion.     

Origin of lipofuscin granules in hybridoma cell culture

Central Research Laboratory, Kaunas Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR J. J. Bredikis.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 3, pp. 363–367, March, 1989.