Silvio Lippa

Chronic and intermittent hypoxia induce different degrees of myocardial tolerance to hypoxia-induced dysfunction

Chronic hypoxia (CH) is believed to induce myocardial protection, but this is in contrast with clinical evidence. Here, we test the hypothesis that repeated brief reoxygenation episodes during prolonged CH improve myocardial tolerance to hypoxia-induced dysfunction. Male 5-week-old Sprague-Dawley rats (n = 7–9/group) were exposed for 2 weeks to CH (F1O2 = 0.10), intermittent hypoxia (IH, same as CH, but 1 hr/day exposure to room air), or normoxia (N, F1O2 = 0.21). Hearts were isolated, Langendorff perfused for 30 min with hypoxic medium (Krebs-Henseleit, PO2 = 67 mmHg), and exposed to hyperoxia (PO2 = 670 mmHg). CH hearts displayed higher end-diastolic pressure, lower rate-pressure product, and higher vascular resistance than IH. During hypoxic perfusion, anaerobic mechanisms recruitment was similar in CH and IH hearts, but less than in N. Thus, despite differing only for 1 hr daily exposure to room air, CH and IH induced different responses in animal homeostasis, markers of oxidative stress, and myocardial tolerance to reoxygenation. We conclude that the protection in animals exposed to CH appears conferred by the hypoxic preconditioning due to the reoxygenation rather than by hypoxia per se.

Determination of copper, zinc, and selenium in human plasma and urine samples by potentiometric stripping analysis and constant current stripping analysis

Potentiometric stripping analysis and constant current stripping analysis are proposed as routine methods for analysis of copper, zinc and selenium in plasma and urine samples. The analytical performance of these methods is comparable with that reported for atomic absorption spectrometry. However the low cost, greater simplicity of the apparatus, and the facility of execution make this methodology a valid candidate for routine application in Clinical Chemistry laboratories.

Quenching of singlet oxygen by D-α-tocopherol in human granulocytes

The ability of D-α-tocopherol to act as a quencher of 1O2 (singlet oxygen) was tested with a biological source of 1O2, namely the phagocytosis activated myeloperoxidase contained in the homogenate of human circulating polymorphonuclear leukocytes. With this system, the 1O2 quenching efficiency of exogenously added D-α-tocopherol was estimated from its inhibitory effect on the luminol amplified chemiluminescence. This inhibitory effect was dose dependent. D-α-tocopherol was also efficient in quenching the chemiluminescence generated through the H2O2-horseradish system. In both systems the quenching effect may be almost entirely “physical”, since very little tocopherol was destroyed when compared to the relatively large amount of H2O2 consumed.

Serum Fatty Acids and Cardiovascular Risk Factors in Sudden Sensorineural Hearing Loss: A Case-Control Study

Objectives: We analyzed the relationships between sudden sensorineural hearing loss (SSNHL) and serum levels of fatty acids, total cholesterol, low-density lipoproteins (LDLs), and the antioxidant coenzyme Q10. Methods: Forty-three patients with SSNHL and 43 healthy subjects were enrolled in the study. The main outcome measures were serum levels of fatty acids, coenzyme Q10, total cholesterol, and LDLs. Results: On univariate logistic regression analysis, high levels of total cholesterol (p < 0.001), LDLs (p = 0.024), behenic acid (p < 0.001), docosahexaenoic acid (p < 0.001), linolenic acid (p = 0.017), and oleic acid (p < 0.001) and low levels of coenzyme Q10 (p < 0.001) and nervonic acid (p < 0.001) were associated with an elevated risk of SSNHL. On multivariate analysis, only hypercholesterolemia (p = 0.15) and low levels of coenzyme Q10 (p = 0.02) and nervonic acid (p = 0.005) were significantly associated with SSNHL. Conclusions: This is the first report of low serum levels of nervonic acid as an independent risk factor for SSNHL. Considering that hypercholesterolemia, high serum levels of LDL, and low serum levels of the antioxidant coenzyme Q10 were associated with SSNHL as well, we hypothesize that saturated fatty acids may play a role in determining the dysmetabolic state in a subset of SSNHL patients. Together, these findings suggest that not only total cholesterol and LDL levels, but also fatty acid determination, may help identify SSNHL patients with cardiovascular risk factors.

Coenzyme Q 10 and cardiovascular risk factors in idiopathic sudden sensorineural hearing loss patients.

Objectives: We investigated the association of idiopathic sudden sensorineural hearing loss (ISSNHL) with coenzyme Q (CoQ) and cardiovascular risk factors. Study Design: A prospective study. Setting: Hospital center. Patients: Thirty Italian patients with ISSNHL and 60 healthy Italian subjects. Intervention: Diagnostic. Main Outcome Measures: Evaluation of serum CoQ levels and cardiovascular risk factors (total cholesterol, low-density lipoprotein [LDL], homocysteine [HCY]). The results were compared with variance analysis and Students t test. Univariate and multivariate analysis were used to evaluate the association between ISSNHL and CoQ, total cholesterol, LDL, and HCY levels. Results: In our series, we found a significant association between ISSNHL and high total cholesterol (p < 0.05), high LDL (p = 0.021), and low CoQ (p < 0.05) levels. We did not find a significant association between ISSNHL and HCY levels. In the univariate analysis, low levels of CoQ, high levels of total cholesterol, and LDL were found to be significantly associated with ISSNHL. In the multivariate analysis, only high levels of total cholesterol and low levels of CoQ remained significantly associated with a high risk of sudden sensorineural hearing loss. Conclusion: The studies regarding the role of cardiovascular risk factors in ISSNHL are not conclusive. This is the first report regarding the association of ISSNHL and low serum levels of the antioxidant CoQ. Further studies are needed to investigate the role of antioxidants, including CoQ, in ISSNHL.

Serum Coenzyme Q10 in Uremic Patients on Chronic Hemodialysis

In a group of 48 chronic hemodialysis patients, serum levels of coenzyme Q10 (CoQ) have been measured and appeared abnormally low in 62% of cases. Figures were positively correlated to those of serum vitamin E (vit E), although the latter were within a normal range. The chronic hemodialysis (CHD) patients with normal serum values of CoQ exhibited higher blood triglycerides. Pathologically low levels of serum vit E were found only in uremic subjects on conservative regimen with dietary restrictions and low compliance to protein-caloric intake. The reduced CoQ levels may contribute to the defective serum antioxidant activity and the increased peroxidative damage in uremic patients on CHD.

Coenzyme Q10 levels, plasma lipids and peroxidation extent in renal failure and in hemodialytic patients.

Coenzyme Q10 (CoQ10), vitamin E, triglycerides and conjugated dienes were measured in a group of 48 patients on chronic hemodialysis, in 15 uremic patients and in a control group of 10 normal subjects. CoQ10 levels were significantly lower (P < 0.001) in both hemodialytic and uremic patients compared with the normal group whereas triglycerides were significantly higher (P < 0.001) with respect to both normal subjects and uremic patients. Conjugated dienes were significantly higher (P < 0.001) in both hemodialytic and uremic patients with respect to normal subjects. The predialytic values of vitamin E were higher in hemodialytic patients with respect to both normal subjects and uremic patients whereas the postdialytic values were in the normal range. A restoration mechanism of vitamin E after hemodialytic treatment was hypothesized.

Effect of general anesthetics on human granulocyte chemiluminescence.

The effect of general anesthetics on human granulocyte ‘phagocytic capacity’ was tested, both in vivo and in vitro, by means of chemiluminescence. Halothane and ethrane produced a consistent degree of chemiluminescence inhibition, which, in vitro, was clearly dose-dependent.

Plasma levels of coenzyme Q(10), vitamin E and lipids in uremic patients on conservative therapy and hemodialysis treatment: some possible biochemical and clinical implications.

Coenzyme Q(10) (CoQ(10)), vitamin E, total cholesterol, HDL-cholesterol (HDLC) and triglycerides were measured in the plasma of 62 patients with kidney failure, 46 under hemodialysis treatment and 16 under conservative therapy, and 95 controls. The sum of LDL-cholesterol (LDL-C) and VLDL-cholesterol (VLDL-C) was also calculated for each patient. The ratio CoQ(10)/LDL-C+VLDL-C in both conservative therapy and hemodialysis populations was significantly lower (P<0.001) compared with normal controls and remained unchanged after the dialysis treatment. On the contrary the ratio vitamin E/LDL-C+VLDL-C was normal but decreased significantly (P<0.02) after each dialysis. Since coenzyme Q is the main inhibitor of the prooxidant action of vitamin E, it was hypothesized that its decrease in both the populations examined could make the lipoproteins of these patients more vulnerable to a peroxidative attack.

Recombinant interferon α-2b and coenzyme Q10 as a postsurgical adjuvant therapy for melanoma: A 3-year trial with recombinant interferon-α and 5-year follow-up

Early surgical intervention remains the most successful therapy for melanoma. Despite better outcomes observed in soft tissue and lymph node metastases, the results of pharmacological therapies are still disappointing. Currently, there is no standard adjuvant therapy for melanoma. Low concentrations of coenzyme Q10 have been demonstrated in melanoma cell lines and in sera of melanoma patients. These data and the results of clinical trials of patients with other advanced cancers prompted this study of the long-term administration of an optimized dose of recombinant interferon &agr;-2b and coenzyme Q10 to patients with stage I and II melanoma. A 3-year trial envisaging uninterrupted treatment with low-dose recombinant interferon &agr;-2b (9 000 000 000 IU weekly) administered twice daily and coenzyme Q10 (400 mg/day) was conducted in patients with stage I and II melanoma (American Joint Committee on Cancer criteria 2002) and surgically removed lesions. Treatment efficacy was evaluated as incidence of recurrences at 5 years. All patients completed the treatment and the follow-up. Significantly different rates of disease progression were observed in the interferon+coenzyme Q10 and the interferon group for both stages. No patient withdrew from the study owing to side effects. Long-term administration of an optimized dose of recombinant interferon &agr;-2b in combination with coenzyme Q10 seemed to induce significantly decreased rates of recurrence and had negligible adverse effects. A survival study could not be undertaken owing to the small patient sample and the short duration of follow-up.