[The histopathological observation of the salivary gland in hamsters with streptozotocin induced diabetes].

It has been reported that the natural defence mechanisms against bacterial infection decreases in diabetic patients. Saliva and salivary gland have an important role to keep healthy condition in oral cavity. Thus, it is possible that saliva from diabetic subject may influence to a development of dental caries. The purpose of this study is to examine the histopathological changes and excretory function of the salivary glands of hamsters with streptozotocin (SZ) induced diabetes. Male hamsters were provided in this experiment at 8 weeks after a single i.p. injection with a dose of SZ (65 mg/kg b. wt.). The flow rate of saliva was determined by stimulation with pilocarpine (8 mg/kg b. wt.). Three major salivary glands and pancreas were obtained from these animals. No difference between diabetic and non-diabetic animals in the flow rate of saliva and wet weight of submandibular and sublingual gland was observed. Pathological finding of salivary gland was not observed in both of the 2 groups of animals but the wet weight of the parotid gland of diabetic hamsters was heavier than that of the non-diabetic hamsters. Moreover, an enlargement of some acinus cells was observed only in the parotid gland of diabetic hamsters.

Coenzyme Q10: clinical benefits with biochemical correlates suggesting a scientific breakthrough in the management of chronic heart failure.

There are obviously several causes of myocardial dysfunction but energy deficiency of the myocytes may play a significant role and probably is a common mechanism during the progression of myocardial failure. Theoretically, a poor utilization efficiency of oxygen may be due to exhaustion of the myocardial stores of bioenergetics. In this report the authors review their biochemical results from measurements of coenzyme Q10 (CoQ10) levels in blood and human endomyocardial biopsies using an HPLC method from patients with suspected myocardial disease (n = 45). The levels of CoQ10, which has a key role in the respiratory chain and the synthesis of ATP, was found to be significantly decreased in various groups of patients with myocardial failure (dilated and restrictive cardiomyopathy and alcoholic heart disease) as compared to "normal" myocardium (0.42 +/- 0.04 micrograms/mg dry weight). The deficiency of CoQ10 was more pronounced with increasing symptoms; e.g. patients with dilated cardiomyopathy in NYHA Classes III and IV had lower tissue CoQ10 content than those of Classes I and II (0.28 +/- 0.04 vs. 0.37 +/- 0.06 micrograms/mg, p less than 0.001). Nearly two thirds of a series of 40 patients in severe heart failure (Classes III and IV) treated with CoQ10, 100 mg daily, in an open, controlled design showed subjective and objective improvement. Clinical responders were 69% and 43% of patients with cardiomyopathy and ischaemic heart disease, respectively. The results suggest that CoQ10 is a novel and effective breakthrough in heart-failure therapy and it appears safe, as no adverse reactions were registered. The through in heart-failure therapy and it appears safe, as no adverse reactions were registered.(ABSTRACT TRUNCATED AT 250 WORDS)

Pronounced increase of survival of patients with cardiomyopathy when treated with coenzyme Q10 and conventional therapy.

During 1982-86, 43/137 patients with cardiomyopathy, Classes II, III and IV, had ejection fractions (EF) below 40%, and a mean EF of 25.1 +/- 10.3%. During treatment of these 43 patients with coenzyme Q10 (CoQ10), EF increased to 41.6 +/- 14.3% (p less than 0.001) over a mean period of 3 months (range, 2-4 months). At four subsequent periods up to 36 months. EF ranged from 43.1 +/- 13.3 to 49.7 +/- 6.4% (each period, p less than 0.001). The mean CoQ10 control blood level was 0.85 +/- 0.26 micrograms/ml which increased on treatment to 1.7 to 2.3 micrograms/ml for five periods up to 36 months (each period, p less than 0.001). The survival rates for all 137 patients treated with CoQ10 and for the 43 patients with EF below 40% were both about 75%/46 months. These two survival rates were comparable between 24 and 46 months, which is of extraordinary significance and importance when compared to survival of about 25%/36 months for 182 patients with EF below 46% on conventional therapy without CoQ10. The improved cardiac function and pronounced increase of survival show that therapy with CoQ10 is remarkably beneficial due to correction of CoQ10 deficiency in mechanisms of bioenergetics.

Coenzyme Q10 and key enzyme activities in papillary muscle related to left ventricle function in mitral valve disease.

Coenzyme Q10 (CoQ10) was studied in papillary muscle from 18 patients (52-67 years, 2 females) subjected to open heart surgery due to mitral valve disease. In addition the enzyme activities of lactate dehydrogenase (LD) with its five isozymes, citrate synthase (CS) and mitochondrial CK (CK-MIT) were determined. Myocardial function was assessed by means of left ventricle (LV) angiography. CoQ10 averaged 0.39 (range 0.26-0.59) micrograms x mg-1 dw. On an individual basis CoQ10 was related to CS activity although not as closely as CK-MIT (r = 0.45, p less than 0.05 versus r = 0.86, p less than 0.001). The ratio (CoQ10) x (CS activity)-1 was calculated to represent mitochondrial quality. The level of LD3 fraction increase was used to mark for the degree of metabolic stress in the heart. LD3 fraction was negatively related to the quality index (r = -0.71, p less than 0.001). Thus, those with a low CoQ10 per unit of CS activity had also a high LD3 isozyme fraction. In a subset of 12 patients with isolated mitral regurgitation due to myxomatous valve degeneration, CoQ10 and the ratio CoQ10 over CS decreased with the degree of LV function impairment (r = -0.58, p less than 0.05 and r = -0.68, p less than 0.05, respectively). The quality index takes into account not only enzyme activity but also the potential for control of free oxygen radicals.

Effective and safe therapy with coenzyme Q10 for cardiomyopathy.

Coenzyme Q10 (CoQ10) is indispensable in mitochondrial bioenergetics and for human life to exist. 88/115 patients completed a trial of therapy with CoQ10 for cardiomyopathy. Patients were selected on the basis of clinical criteria, X-rays, electrocardiograms, echocardiography, and coronary angiography. Responses were monitored by ejection fractions, cardiac output, and improvements in functional classifications (NYHA). Of the 88 patients 75%-85% showed statistically significant increases in two monitored cardiac parameters. Patients with the lowest ejection fractions (approx. 10%-30%) showed the highest increases (115 delta %-210 delta %) and those with higher ejection fractions (50%-80%) showed increases of approx. 10 delta %-25 delta % on therapy. By functional classification, 17/21 in class IV, 52/62 in class III, and 4/5 in class II improved to lower classes. Clinical responses appeared over variable times, and are presumably based on mechanisms of DNA-RNA-protein synthesis of apoenzymes which restore levels of CoQ10 enzymes in a deficiency state. 10/21 (48%) of patients in class IV, 26/62 (42%) in class III, and 2/5 (40%) in class II had exceptionally low control blood levels of CoQ10. Clinical responses on therapy with CoQ10 appear maximal with blood levels of approx. 2.5 micrograms CoQ10/ml and higher during therapy.

A superior analysis of coenzyme Q10 in blood of humans, rabbits and rats for research.

The quantitative analysis of coenzyme Q10 (CoQ10) in samples of whole human blood has been refined to allow a 2- to 3-fold increase in the number of analyses per day, and reduction of cost to approximately 15% of the previous cost. The method is simple yet maintains reliability. The standard error was 0.2% (n = 6). The variation in blood levels of CoQ10 for human subjects for each of three months was approximately 5% in comparison with the control value (n = 5). For 30 human males, of 18-50 years (26 +/- 6) in age, and for 30 human females, of 18-50 years (26 +/- 9), the mean blood level of CoQ10 was 0.71 +/- 0.13 microgram/ml and 0.70 +/- 0.18 microgram/ml respectively. The mean blood levels of CoQ10 of rabbits (n = 28) was 0.29 +/- 0.07 micrograms/ml, and that for rats (n = 29) was 0.23 +/- 0.03 micrograms/ml.

Biochemical deficiencies of coenzyme Q10 in HIV-infection and exploratory treatment.

AIDS patients (2 groups) had a blood deficiency (p less than 0.001) of coenzyme Q10 vs. 2 control groups. AIDS patients had a greater deficiency (p less than 0.01) than ARC patients. ARC patients had a deficiency (p less than 0.05) vs. control. HIV-infected patients had a deficiency (p less than 0.05) vs. control. The deficiency of CoQ10 increased with the increased severity of the disease, i.e., from HIV positive (no symptoms) to ARC (constitutional symptoms, no opportunistic infection or tumor) to AIDS (HIV infection, opportunistic infection and/or tumor). This deficiency, a decade of data on CoQ10 on the immune system, on IgG levels, on hematological activity constituted the rationale for treatment with CoQ10 of 7 patients with AIDS or ARC. One was lost to follow-up; one expired after stopping CoQ10; 5 survived, were symptomatically improved with no opportunistic infection after 4-7 months. In spite of poor compliance of 5/7 patients, the treatment was very encouraging and at times even striking.

Significance of biological parameters of human blood levels of CoQ10.

Ninety-one men and 143 women who were so-called normal subjects were tested for cardiac performance at rest and their blood levels of co-enzyme Q10 (CoQ10) were determined. In males, a negative relationship between progression of age and cardiac performance, and a positive relationship between progression of age and blood levels of CoQ10 were revealed. In females, a positive relationship between age and blood levels of CoQ10 was found. The mean CoQ10 blood level for both sexes was the same (0.79 +/- 0.20 micrograms/ml for males and 0.79 +/- 0.23 for females). Cardiac performance declines with age in the male population. A decreased biosynthesis and/or incorporation of CoQ10 into mitochondrial structures of muscle cells may occur with age in a normal population.

Levels of salivary lysozyme, lactoperoxidase, and lactoferrin in diabetic hamsters.

In an attempt to clarify the mechanism(s) of increased susceptibility to oral infection in diabetics, we examined the levels of salivary antibacterial factors, including lysozyme, lactoperoxidase, and lactoferrin, in diabetic hamsters whose condition was induced with streptozotocin. Saliva was collected from these hamsters periodically for 19 weeks after the administration of streptozotocin. Diabetes persisted with significant hyperglycemia throughout the experiment after a single injection of streptozotocin. There was no significant difference between groups in the amount of saliva secreted. In diabetic hamsters, lysozyme activity decreased by 56% and lactoperoxidase activity decreased by 53% compared with the control hamsters 19 weeks after the administration of streptozotocin. There was no significant difference between groups in the amount of salivary lactoferrin. However, the ratio of lactoferrin to total protein increased to approximately double the amount of that of the control hamsters. Insulin treatment had a significant effect on lysozyme and lactoperoxidase activity, recovering 73 and 74% those of the controls, respectively, and the ratio of lactoferrin to total salivary protein reverted to normal values. Growth inhibition of Lactobacillus plantarum ATCC 8014 with whole saliva and amylase activity significantly decreased in diabetic hamsters. The position of each protein band of whole saliva on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was almost the same for control and diabetic hamsters; however, there was some variability in band intensity.