Acatalasemia

Summary The abnormalities in acatalasemia at the gene level as well as properties of the residual catalase in Japanese acatalasemia are historically reviewed. The replacement of the fifth nucleic acid, guanine, in the fourth intron by adenine in the acatalasemic gene causes a splicing mutation and hence a deficiency of mRNA. The guanine-to-adenine substitution was detected in two Japanese acatalasemic cases from different families. The properties of the residual catalase are similar to those of normal catalase; the exons are identical. The properties of the residual catalase and the molecular defect in the catalase gene are compared among Japanese, Swiss, and mouse acatalasemias. The physiological role of catalase, as judged from human acatalasemic blood and acatalasemic mice, is also described.     

Acatalasemia in the mouse and other species

Genetic control of the level of blood catalase activity was first demonstrated in 1927. At present, such control has been demonstrated or suggested for nine different species, including man, the most studied. The development of an acatalasemic strain of mice has permitted a wide variety of experimental approaches, including most of those used in humans. Among those approaches which cannot readily be applied to man but have been used in acatalasemic mice are investigations of sensitivity to radiation lethality, mechanism of awareness to radiation, possible use as a model for replacement therapy for inborn errors of metabolism, and catalase in tissues other than erythrocytes. These are described, together with genetic, immunological, and other studies comparable to similar work on acatalasemic humans.This paper was presented at a symposium entitled Genetic Control of Mammalian Metabolism held at The Jackson Laboratory, Bar Harbor, Maine, June 30–July 2, 1969. The symposium was supported in part by an allocation from NIH General Research Support Grant FR 05545 from the Division of Research Resources to The Jackson Laboratory.Work supported by the United States Atomic Energy Commission.     

Glycated albumin and diabetes mellitus

Background

Diabetes is a growing worldwide problem that is strongly associated with atherosclerosis. Screening and intervention for diabetes in the earliest stages are advocated for the prevention of diabetic complications and cardiovascular disease.

Scope of review

This review gives a background of and discusses the potential clinical utility of glycated albumin (GA) in diabetes.

Major conclusions

GA is a ketoamine formed via a non-enzymatic glycation reaction of serum albumin and it reflects mean glycemia over two to three weeks. GA can be used for patients with anemia or hemoglobinopathies for whom the clinically measured hemoglobin A1c level may be inaccurate. Because both serum and plasma samples can be used, GA can be analyzed from the same samples as common biological markers. GA is a useful marker for the screening of diabetes in a medical evaluation. It can be also used to determine the effectiveness of treatment before initiating or changing medications for diabetic patients. GA is potentially an atherogenic protein in the development of diabetic atherosclerosis.

General significance

GA measurement is useful as part of a routine examination to screen for both diabetes and atherosclerosis. This article is part of a Special Issue entitled Serum Albumin.     

Erectile dysfunction and diabetes mellitus

Background: Erectile dysfunction (ED) is highly prevalent, affecting ≥50% of men with diabetes mellitus (DM) worldwide.Objective: This article reviews current knowledge on the epidemiology and underlying pathophysiology of ED in men with DM, diagnostic modalities, and treatment options.Methods: A MEDLINE literature search was conducted for articles published in English from inception of the database through November 2008, using the terms erectile dysfunction, diabetes, epidemiology, pathophysiology, phosphodiesterase inhibitors, intracavernosal injection, and penile prosthesis. Data on the epidemiology, diagnosis, and treatment of ED were extracted from all relevant articles.Results: The literature search revealed 685 original articles and reviews, 67 of which were selected for inclusion in this review. DM may cause ED through a number of pathophysiologic changes, including neuropathy, endothe-lial dysfunction, cavernosal smooth muscle structural/functional changes, hormonal changes, and psychological effects. The diagnosis of ED in men with DM is based on their sexual and medical histories and results of validated questionnaires such as the International Index of Erectile Function. Laboratory examinations are usually limited to testosterone and prolactin levels that may independently contribute to ED because specialized examinations are not necessary in most diabetic men with ED. The first step in the treatment of ED in men with DM includes glycemic control and treatment of diabetic comorbidities. The associated hypogonadism must also be treated; otherwise, pharmacologic treatment may be less efficacious or not efficacious at all. Phosphodiesterase type-5 (PDE-5) inhibitors have revolutionized the treatment of ED, and they are considered first-line treatment, with a mean efficacy rate of 50% and a favorable safety profile. Intracavernous administration of vasoactive drugs is the second-line medical treatment when PDE-5 inhibitors have failed. Alprostadil is the most widely used drug for this condition, but the combination of papaverine, phentolamine, and alprostadil represents the most efficacious pharmacologic treatment option for patients whose ED does not respond to monotherapy. Excellent functional and safety results have been reported for penile prosthesis implantation, and this approach, along with proper counseling, can be considered for selected patients with treatment-refractory ED.Conclusions: ED is common in men with DM, who represent one of the most difficult-to-treat subgroups of ED patients. PDE-5 inhibitors are the first-line treatment option, followed by intracavernosal injections and implantation of a penile prosthesis.     

Fibrinolysis in diabetes mellitus

In 198 diabetic patients of type I and type II and in 111 healthy persons of a control group the activity of fibrinolysis was investigated before and after a venous occlusion test of ten minutes. Spontaneous fibrinolysis was significantly diminished in diabetics of both types in comparison to the control group. A relationship to the degree of seriousness of retinopathy could not be identified in type I. The activity of fibrinolysis decreased in all test persons in old age. In diabetics patients of type II as well as in that age group being more than 56 years old there were smaller activities of fibrinolysis at higher stages of retinopathy. A negative linear correlation of this spontaneous activity of fibrinolysis could be found for the duration of the disease as well as for age. Different forms of diabetic therapy and the sex allowed no influence of the activity of fibrinolysis to be recognized. An increase of the activity of fibrinolysis after congestion could be established in diabetics as well as in the control group. After venous congestion the fibrinolytic activity showed no differences any longer in diabetics and in the control group, with age, duration of the disease and form of therapy being taken into consideration. Before and after venous congestion a negative linear correlation could be revealed between the activity of fibrinolysis and the height of blood sugar level. Therefore, the real blood sugar concentration should be taken into account in evaluating the fibrinolytic activity.