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Biomedical subjects

K Folkers

Publications and source records attributed to K Folkers.

At least 37 records · Page 2Linked to original sources
PubMed1994

Apparent partial remission of breast cancer in 'high risk' patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10.

Thirty-two typical patients with breast cancer, aged 32-81 years and classified 'high risk' because of tumor spread to the lymph nodes in the axilla, were studied for 18 months following an Adjuvant Nutritional Intervention in Cancer protocol (ANICA protocol). The nutritional protocol was added to the surgical and therapeutic treatment of breast cancer, as required by regulations in Denmark. The added treatment was a combination of nutritional antioxidants (Vitamin C: 2850 mg, Vitamin E: 2500 iu, beta-carotene 32.5 iu, selenium 387 micrograms plus secondary vitamins and minerals), essential fatty acids (1.2 g gamma linolenic acid and 3.5 g n-3 fatty acids) and Coenzyme Q10 (90 mg per day). The ANICA protocol is based on the concept of testing the synergistic effect of those categories of nutritional supplements, including vitamin Q10, previously having shown deficiency and/or therapeutic value as single elements in diverse forms of cancer, as cancer may be synergistically related to diverse biochemical dysfunctions and vitamin deficiencies. Biochemical markers, clinical condition, tumor spread, quality of life parameters and survival were followed during the trial. Compliance was excellent. The main observations were: (1) none of the patients died during the study period. (the expected number was four.) (2) none of the patients showed signs of further distant metastases. (3) quality of life was improved (no weight loss, reduced use of pain killers). (4) six patients showed apparent partial remission.

Adult↗
PubMed1994

Effect of topical application of coenzyme Q10 on adult periodontitis.

Topical application of Coenzyme Q10 (CoQ10) to the periodontal pocket was evaluated with and without subgingival mechanical debridement. Ten male patients with adult periodontitis participated and 30 periodontal pockets were selected. During the first 3 weeks, the patients did not receive any periodontal therapy except the topical application of CoQ10. After the first 3-week period, root planning and subgingival scaling were performed in all sites. CoQ10 was applied in 20 of the pockets once a week for a period of 6 weeks. Soybean oil was applied to the remaining 10 sites as a control. In the first 3-week period, significant reductions in gingival crevicular fluid flow, probing depth and attachment loss were found only at experimental sites. After mechanical subgingival debridement, significant decreases in the plaque index, gingival crevicular fluid flow, probing depth and attachment loss were found both at experimental and control sites. However, significant improvements in the modified gingival index, bleeding on probing and peptidase activity derived from periodontopathic bacteria were observed only at experimental sites. These results suggest that topical application of CoQ10 improves adult periodontitis not only as a sole treatment but also in combination with traditional nonsurgical periodontal therapy.

Administration, Topical↗
PubMed1994

Treatment of essential hypertension with coenzyme Q10.

A total of 109 patients with symptomatic essential hypertension presenting to a private cardiology practice were observed after the addition of CoQ10 (average dose, 225 mg/day by mouth) to their existing antihypertensive drug regimen. In 80 per cent of patients, the diagnosis of essential hypertension was established for a year or more prior to starting CoQ10 (average 9.2 years). Only one patient was dropped from analysis due to noncompliance. The dosage of CoQ10 was not fixed and was adjusted according to clinical response and blood CoQ10 levels. Our aim was to attain blood levels greater than 2.0 micrograms/ml (average 3.02 micrograms/ml on CoQ10). Patients were followed closely with frequent clinic visits to record blood pressure and clinical status and make necessary adjustments in drug therapy. Echocardiograms were obtained at baseline in 88% of patients and both at baseline and during treatment in 39% of patients. A definite and gradual improvement in functional status was observed with the concomitant need to gradually decrease antihypertensive drug therapy within the first one to six months. Thereafter, clinical status and cardiovascular drug requirements stabilized with a significantly improved systolic and diastolic blood pressure. Overall New York Heart Association (NYHA) functional class improved from a mean of 2.40 to 1.36 (P < 0.001) and 51% of patients came completely off of between one and three antihypertensive drugs at an average of 4.4 months after starting CoQ10. Only 3% of patients required the addition of one antihypertensive drug. In the 9.4% of patients with echocardiograms both before and during treatment, we observed a highly significant improvement in left ventricular wall thickness and diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A one year bioavailability study of coenzyme Q10 with 3 months withdrawal period.

Twenty-one healthy subjects received oral Coenzyme Q10 supplementation in soft capsules of 30 mg t.i.d. for 9 months, followed by a withdrawal period of 3 months. Blood samples were taken before start of supplementation, after 3 and 9 months of supplementation, and finally 3 months after withdrawal. Average blood coenzyme Q10 concentration increased from about 1 mg/l before supplementation to about 2 mg/l after 3 and 9 months of supplementation, and returned to the pretreatment level after withdrawal. The rise of coenzyme Q10 concentration was statistically significant (P < 0.001, t-test).

Administration, Oral↗
PubMed1994

New, highly active antagonists of LHRH with acylated lysine and p-aminophenylalanine in positions 5 and 6.

A series of antagonists of the luteinizing hormone releasing hormone (LHRH) with substitutions in position 5 and/or 6 that included acylated lysine or p-aminophenylalanine were synthesized, characterized and tested for antiovulatory activity (AOA) in rats, and histamine releasing activity. Some of these antagonists were considerably more soluble at neutral pH than antagonists like Antide. Of 37 new antagonists, the best physico-chemical and biological properties were found for the following two analogs: NAcDNal-DCpa-DPal-Ser-PicLys-D(PicSar)Lys- Leu-ILys-Pro-DAlaNH2 (named Sartide) and NAcDNal-DCpa-DPal-Ser-Tyr-D(PicSar)Lys-Leu-IL ys-Pro-DAlaNH2. They are both soluble in water, inhibit ovulation completely at 0.5 microgram per rat, and have ED50 values for histamine release of about 30 micrograms/mL.

Amino Acid Sequence↗
PubMed1993

The activities of coenzyme Q10 and vitamin B6 for immune responses.

Coenzyme Q10 (CoQ10) and vitamin B6 (pyridoxine) have been administered together and separately to three groups of human subjects. The blood levels of CoQ10 increased (p < 0.001) when CoQ10 and pyridoxine were administered together and when CoQ10 was given alone. The blood levels of IgG increased when CoQ10 and pyridoxine were administered together (p < 0.01) and when CoQ10 was administered alone (p < 0.05). The blood levels of T4-lymphocytes increased when CoQ10 and pyridoxine were administered together (p < 0.01) and separately (p < 0.001). The ratio of T4/T8 lymphocytes increased when CoQ10 and pyridoxine were administered together (p < 0.001) and separately (p < 0.05). These increases in IgG and T4-lymphocytes with CoQ10 and vitamin B6 are clinically important for trials on AIDS, other infectious diseases, and on cancer.

Adult↗
PubMed1993

Survival of cancer patients on therapy with coenzyme Q10.

Over ca. 25 years, assays in animal models established the hematopoietic activities of coenzyme Q's in rhesus monkeys, rabbits, poultry, and children having kwashiorkor. Surprisingly, a virus was found to cause a deficiency of CoQ9. Patients with AIDS showed a-"striking"-clinical response to therapy with CoQ10. The macrophage potentiating activity of CoQ10 was recorded by the carbon clearance method. CoQ10 significantly increased the levels of IgG in patients. Eight new case histories of cancer patients plus two reported cases support the statement that therapy of cancer patients with CoQ10, which has no significant side effect, has allowed survival on an exploratory basis for periods of 5-15 years. These results now justify systematic protocols.

Aged↗
PubMed1993

A new method to determine the level of coenzyme Q10 in one drop of human blood for biomedical research.

This method has been designed to determine the levels of CoQ10 in human blood which utilizes only one drop of blood (0.05 ml). This method encourages and facilitates more frequent monitoring of blood levels of CoQ10, and of clinical importance, reveals the presence or absence of compliance. CoQ11 was used as an internal standard. The mean recovery of CoQ10 was 96%. The correlation coefficient between using 1.0 ml and 0.1 ml of blood and between using 1.0 and 0.05 ml was 0.997 in the two comparisons. Therefore, it can be accurate to monitor the level of CoQ10 in a -"finger-prick"-drop of blood, and at least 24 such determinations can be conducted in a 2-day period.

Coenzymes↗
PubMed1993

Heart muscle ubiquinone and plasma antioxidants following cardiac transplantation.

Nine patients who underwent heart transplantation (one female; average age 48 +/- 11, range 19-58 years) were followed in respect to contents of right-sided heart septum, blood and plasma ubiquinone (UQ), plasma alpha-tocopherol (alpha T), and plasma free cholesterol (FC). In contrast to healthy persons, substantial inter- and intraindividual variations were observed; individually low values were seen with rejection. Heart muscle UQ in well-treated patients averaged 0.33 +/- 0.08, range 0.06-0.58 micrograms mg-1 (0.38 +/- 0.09 mumol g-1 dry weight) and was not different from healthy individuals. Plasma UQ, alpha T; and FC averaged 0.63 +/- 0.33 micrograms ml-1 (P < 0.05 versus sedentary controls), 8.1 +/- 4.0 micrograms ml-1 (P < 0.01), and 0.52 +/- 0.23 mg ml-1 (P < 0.05). Corresponding molar values were 0.73 +/- 0.37 (UQ), 2.0 +/- 1.1 mumol l-1 (alpha T), and 1.42 +/- 0.54 mmol l-1 (FC). Blood and plasma UQ values were identical. A saturation like relationship was found between heart and blood UQ:blood contents below 0.7 micrograms ml-1 (0.8 mumol l-1) corresponded to markedly lowered heart contents. In four patients in whom blood samples were taken close to a fatal complication it averaged 0.42 micrograms ml-1 (0.49 mumol l-1, P < 0.01). When low heart muscle and blood ubiquinone were present, other variables such as left ventricle cardiac output or cycle ergometer performance was markedly impaired. Plasma UQ and alpha T covaried with a marker of the lipoidal deposit volume, plasma FC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Ubiquinone and alpha-tocopherol in plasma; means of translocation or depot.

Ubiquinone (UQ) and alpha-tocopherol (AT) are two highly lipophilic antioxidants which can be dissolved only in lipid layers or attached to protein structures. Analyses of both UQ and AT in whole blood and plasma demonstrate identical values, which excludes any significant allocation to blood cells. The lipoidic plasma structures constitute the plasma lipoprotein fractions of high (HDL), low (LDL), and very low (VLDL) density in addition to chylomicrons. This means by definition that blood and plasma UQ and AT values are limited if not related to the lipoidic deposit volume. UQ and AT increase linearly with free cholesterol (FC). FC has therefore been suggested to be a good marker for the deposit volume. The ratios UQ and AT over FC--normalized UQ (N-UQ) and normalized AT (N-AT)--have been computed for inter- and intraindividual comparisons. With a plasma UQ content of 1 microgram/ml (approximately 1 mumol/l) and a plasma volume of 41, UQ makes up about 15% of the total heart content or under 1% of UQ in skeletal muscle. The corresponding value for the total extracellular UQ content is less than 2%. This means that extracellular UQ has no or a very minor role as a UQ depot. The same is true for AT. However, for transportation and allocation determinations of N-UQ and N-AT are relevant. Assuming only a lipoprotein-related transportation, healthy persons have saturated plasma UQ and AT values in only 25% and 10% of the population, respectively. All patient categories studied have been found nonsaturated. VLDL plus LDL constitute some 90% of the UQ deposit volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1993

Isolated diastolic dysfunction of the myocardium and its response to CoQ10 treatment.

Symptoms of fatigue and activity impairment, atypical precordial pain, and cardiac arrhythmia frequently precede by years the development of congestive heart failure. Of 115 patients with these symptoms, 60 were diagnosed as having hypertensive cardiovascular disease, 27 mitral valve prolapse syndrome, and 28 chronic fatigue syndrome. These symptoms are common with diastolic dysfunction, and diastolic function is energy dependent. All patients had blood pressure, clinical status, coenzyme Q10 (CoQ10) blood levels and echocardiographic measurement of diastolic function, systolic function, and myocardial thickness recorded before and after CoQ10 replacement. At control, 63 patients were functional class III and 54 class II; all showed diastolic dysfunction; the mean CoQ10 blood level was 0.855 micrograms/ml; 65%, 15%, and 7% showed significant myocardial hypertrophy, and 87%, 30%, and 11% had elevated blood pressure readings in hypertensive disease, mitral valve prolapse and chronic fatigue syndrome respectively. Except for higher blood pressure levels and more myocardial thickening in the hypertensive patients, there was little difference between the three groups. CoQ10 administration resulted in improvement in all; reduction in high blood pressure in 80%, and improvement in diastolic function in all patients with follow-up echocardiograms to date; a reduction in myocardial thickness in 53% of hypertensives and 36% of the combined prolapse and fatigue syndrome groups; and a reduced fractional shortening in those high at control and an increase in those initially low.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Myocardial preservation by therapy with coenzyme Q10 during heart surgery.

Coenzyme Q10 (CoQ10) is a natural and essential cofactor in the heart. It is the primary redox coupler in the respiratory chain, a potent free radical scavenger, and a superoxide inhibitor. In this study the myocardial protective effects of CoQ10 were determined in high-risk (n = 10) patients during heart surgery compared to that found in placebo controls (n = 10). In both groups, there was a blood CoQ10 deficiency (< 0.6 microgram/ml), low cardiac index (CI < 2.4 l/m2 per minute), and low left ventricular ejection fraction (LVEF < 35%) before treatment. CoQ10 (100 mg per day) was given orally for 14 days before and 30 days after surgery. Presurgical CoQ10 treatment significantly (P < 0.01) improved blood and myocardial CoQ10 and myocardial ATP compared to that found in the control group. Cardiac functions (CI and LVEF) were improved but not significantly. After cardiac cooling, rewarming, and reperfusion; blood and tissue CoQ10 and tissue ATP levels were maintained in the normal ranges in the CoQ10 patients. Cardiac pumping (CI) and LVEF were significantly (P < 0.01) improved. The recovery course was short (3-5 days) and uncomplicated. In the control group blood and tissue CoQ10, tissue ATP levels, and cardiac functions were depressed after surgery. The recovery course was long (15-30 days) and complicated. Positive relationships between blood and myocardial CoQ10, myocardial ATP, cardiac function, and the postoperative recovery time and course found in both study groups show the therapeutic benefits of CoQ10 in preserving the myocardium during heart surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Synthesis and bioassay of LHRH-antagonists with N-Ac-D-O-phenyltyrosine and N-Ac-D-3-(2-dibenzofuranyl)alanine in position 1.

N-Ac-D-O-phenyltyrosine was synthesized via the corresponding azlactone. Resolution of the DL methyl esters was achieved by Subtilisin Carlsberg. Treatment with palladium(II) acetate in trifluoroacetic acid converted N-Ac-D-O-phenyltyrosine into N-Ac-D-3-(2-dibenzofuranyl)alanine. These two amino acids were incorporated instead of N-Ac-D-2-Nal into position 1 of the LHRH-antagonist (N-Ac-D-2-Nal1, D-p-ClPhe2, D-3-Pal3, c-PzACAla5, D-PicLys6, ILys8,D-Ala10)-LHRH. The more rigid N-Ac-D-3-(2-dibenzofuranyl)alanine was structurally more effective than N-Ac-D-O-phenyltyrosine; the AOAs for the corresponding analogs were 82 and 38%, respectively, at 0.5 micrograms. Replacement of c-PzACAla in position 5 by O-phenyltyrosine significantly decreased potency.

Amino Acid Sequence↗
PubMed1992

Therapy with coenzyme Q10 of patients in heart failure who are eligible or ineligible for a transplant.

Twenty years of international open and seven double blind trials established the efficacy and safety of coenzyme Q10 (CoQ10) to treat patients in heart failure. In the U.S., ca. 20,000 patients under 65 years are eligible for transplants, but donors are less than 1/10th of those eligible, and there are many more such patients over 65, both eligible and ineligible. We treated eleven exemplary transplant candidates with CoQ10; all improved; three improved from Class IV to Class I; four improved from Classes III-IV to Class II; and two improved from Class III to Class I or II. After CoQ10, some patients required no conventional drugs and had no limitation in lifestyle. The marked improvement is based upon correcting myocardial deficiencies of CoQ10 which improve mitochondrial bioenergetics and cardiac performance. These case histories, and very substantial background proof of efficacy and safety, justify treating with CoQ10 patients in failure awaiting transplantation.

Adult↗
PubMed1992

Ischaemic heart disease, skeletal muscle fibres and exercise capacity.

Twenty-eight male patients with ischaemic heart disease (IHD) performed OBLA (onset of blood lactate accumulation) exercise stress tests and had muscle biopsies taken from their vastus lateralis muscle the day before coronary bypass grafting. All 28 patients showed the same exercise performance pattern as compared to healthy sedentary, age-matched, controls: a low exercise intensity eliciting a blood lactate concentration of 2.0 mmol x l-1 (WOBLA), WOBLA corresponded to a high fraction (% WOBLA) of WSL (symptom limited or 'maximal' capacity), and a low peak blood lactate concentration. The high % WOBLA and low peak blood lactate indicated a reduced glycogenolytic capacity ('anaerobic' performance). Muscle fibre composition disclosed a high mean value of fast twitch (FT), type II or 'white' muscle fibres, as compared to sedentary healthy controls. This indicated that this patient group constituted an extreme subgroup of the age-matched population. The distorted muscle fibre composition in IHD could reflect both heredity as well as adaptation to physical inactivity, degenerative cytosolic properties, etc. Muscle and blood contents of a mitochondrial electron translocator and nonspecific radical scavenger, ubiquinone or coenzyme Q10(CoQ10), were low, which coincided with an elevated frequency of the fibre subgroup FT(c). The presence of the FT(c) fibre type is assumed to reflect histological trauma.

Adult↗
PubMed1992

Exercise-limiting factors in respiratory distress.

Exercise performance data, circulatory function and respiratory and leg muscle quality, expressed as muscle fiber composition, are reviewed and together with our own data discussed as possible limiting factors for physical performance in chronic obstructive pulmonary disease (COPD). COPD is regarded as synonymous with reduced physical performance, exaggerated breathlessness or dyspnea, muscle hypotrophy and/or wasting and, frequently, malnutrition. Impaired right ventricular circulatory function seems to be essential. The observed preponderance of fast twitch (FT), 'glycogenolytic' and capillary-poor muscle fiber type in the investigated muscles might reflect endowment, a 'hypoxic vasoconstriction'-related downregulation of the other main fiber type: the slow twitch (ST), capillary-rich, fatigue-resistant fiber, and/or selective muscle trauma to ST fibers. Ischemic heart disease (IHD) patients demonstrate a similar fiber type pattern in leg muscles. Both COPD and IHD patients have low leg muscle and plasma deposits of antioxidants such as coenzyme Q10 (CoQ10) and alpha-tocopherol. This could reflect a depressed resistance to radical induced cell trauma and/or malnutrition. The magnitude of the antioxidant reduction is less pronounced in patients rich in FT fibers indicating a ST fiber-related susceptibility to trauma. Treatment of other muscle disorders including heart muscle with, e.g., CoQ10 improves performance due to a causative enhanced antioxidant potential, reduced catabolism and/or an upregulated muscle anabolism, increased mitochondrial volume/function, etc. Such data are lacking in COPD.

Aged↗
PubMed1992

Plasma ubiquinone, alpha-tocopherol and cholesterol in man.

Plasma ubiquinone, coenzyme Q10 or CoQ10 has been analyzed in plasma together with alpha-tocopherol and free cholesterol in healthy sedentary male subjects (SS), endurance trained male athletes (ET) and male patients with severe ischemic heart disease (IHD). Higher means were found in SS compared to both IHD and ET. Moreover, the ratios CoQ10 and alpha-tocopherol over free cholesterol were higher. In all groups significant relationships were found between the two products of the mevalonate pathway: CoQ10 and cholesterol (r ranged 0.66-0.86, p less than 0.01). The two lipophilic antioxidants, CoQ10 and alpha-tocopherol, were interrelated only in IHD (r = 0.86, p less than 0.001), borderline in SS (r = 0.51, p less than 0.05) but not in ET. It is assumed that plasma free cholesterol reflects the capacity to transport lipids and lipophilic compounds in blood. With metabolic stress and an elevated radical formation as in IHD and ET, the lower CoQ10 and alpha-tocopherol to cholesterol ratios mirror a subsequent toll on the scavenging potential. The difference in LDL levels between IHD and ET and the different storage capacity of CoQ10 and alpha-tocopherol might explain the tight coupling in IHD but not in ET. It is possible that the toll reflects both an intra- and extracellular radical quenching activity. The joint effect of the two lipophilic, extracellular antioxidants CoQ10 and alpha-tocopherol role in protecting e.g. LDL particles from peroxidation is suggested.

Cholesterol↗