Effect of Coenzyme Q10 in mitigating oxidative DNA damage in Down syndrome patients, a double blind randomized controlled trial.

Down syndrome (DS) is a chromosomal abnormality (trisomy 21) associated with a complex phenotype. Oxidative stress is known to play a major role in this pathology both due to genetic and epigenetic factors, suggesting that oxidative imbalance contributes to the clinical manifestation of DS. In particular, the implications of oxidative DNA damage in Down syndrome has been linked with neurodegeneration. Here we report the results of a double blind controlled trial aimed at investigating the protective effect of Coenzyme Q(10) on DNA oxidation in this clinical setting using the single cell gel electrophoresis technique.

Coenzyme Q10 and oxidative imbalance in Down syndrome: biochemical and clinical aspects.

Down syndrome (DS) is a chromosomal abnormality (trisomy 21) associated with mental retardation and Alzheimer-like dementia, characteristic change of the individual's phenotype and premature ageing. Oxidative stress is known to play a major role in this pathology since a gene dose effect leads to elevated ratio of superoxide dismutase to catalase/glutathione peroxidase compared to controls in all age categories suggesting that oxidative imbalance contributes to the clinical manifestation of DS. Hyperuricemia is another feature of DS that has an interesting relationship with oxidative stress since uric acid represents an important free radical scavenger. However its formation is connected to the conversion of Xanthine dehydrogenase (XDH) to Xanthine oxidase (XO) which leads to concomitant production of free radicals. Here we report that plasma samples from DS patients in pediatric age, despite an increased total antioxidant capacity, largely due to elevated Uric acid content (UA), present significantly elevated markers of oxidative damage such as increased allantoin levels. Moreover DS plasma samples do not differ from healthy control ones in terms of Coenzyme Q10 and susceptibility to peroxidative stimuli. On the contrary, lymphocyte and platelet CoQ10 content was significantly lower in DS patients, a fact that might underlie oxidative imbalance at a cellular level.

Research and characterization of pathogenic vibrios from bathing water along the Conero Riviera (Central Italy).

The occurrence and pathogenicity of vibrios in bathing water were investigated along the Conero Riviera (Adriatic Sea, Central Italy). Vibrio spp. enumeration was performed on thiosulfate-citrate-bile-salts-sucrose-agar by the membrane filter method, and identification was done through a biochemical protocol. All isolates were tested for the presence of cytotoxicity, protease, lipase, elastase, gelatinase, urease, haemolytic activity, ctx, tdh and trh genes by conventional methods. In all, 200 vibrios were isolated from 132 samples that were analysed. Vibrio harveyi and Vibrio alginolyticus were the species most frequently recovered. All strains were cytotoxic and some of them showed protease, gelatinase, lipase, elastase, urease and haemolytic activity. One isolate of V. alginolyticus and one of V. harveyi had the trh gene, while another strain of V. harveyi and one of Vibrio parahaemolyticus had the ctx gene. These results demonstrate the presence of potentially pathogenic vibrios in the Conero Riviera and the risk of infection due to bathing water exposure.

Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity.

Paraoxonase, an enzyme associated with high density lipoproteins (HDL), plays an important role in the anti-oxidant and anti-inflammatory properties exerted by HDL. Increasing evidence supports a role of free radicals and oxidative stress in the inflammatory processes and in the pathogenesis of multiple sclerosis (MS). The aim of this study was to further investigate the relationship between oxidative damage and MS; therefore we compared the paraoxonase activity and levels of cholesteryl ester hydroperoxides (CE-OOH), as marker of lipid peroxidation, in plasma isolated from healthy subjects (n = 89) and from MS patients (n = 24) in the early stage disability (EDSS<3.5). Our results demonstrated for the first time that the activity of paraoxonase in the plasma of MS subjects was significantly lower with respect to controls (P <0.001). Moreover, our results showed a significant increase in the levels of CE-OOH in plasma from MS subjects (P<0.001). CE-OOH are biologically active substances derived from the oxidation of cholesteryl ester localized in the hydrophobic core of plasma lipoproteins (HDL, LDL). Therefore, our study demonstrates alterations of lipoprotein peroxidation in MS and provides further evidence that oxidative stress and impairment of the anti-oxidant system may play a role in MS.

Costs and quality in loco-regional anesthesia.

Quality can be considered to be a strategic element in the political process of planning and implementation of health and social care, resulting in a form of guarantee for the public through encouraging constructive competition between providers and reducing wasting and poor management. This should also be applied to managing loco-regional anesthesia. Competition is constant between treatments currently available together with a focus on quality and costs. This brings about strict controls on health care costs which should then be based on the evaluation of the results obtained in terms of health. It is obvious that costs for materials, time spent for an intervention, staff employed and structures required to carry it out are unavoidable. Quality is that treatment which maximises the patient's well-being following evaluation of the expected risks and benefits involved in the overall treatment. Acute pain is suffered by surgical patients either due to pre-existing disease, surgical intervention or due to a combination of both these situations. There is a high incidence of postoperative pain. In fact, more than 75% of postoperative patients report to have suffered moderate to severe pain. The same results have been reported in pediatrics and oncology: these results should always encourage the application of clinical quality, taking into consideration the costs involved when carrying out loco-regional anesthesia which aims at improving patient's outcome when undergoing surgical intervention.

Coenzyme Q10 evaluation in pituitary-adrenal axis disease: preliminary data.

In previous works we have demonstrated plasma CoQ10 alterations in pituitary diseases, such as acromegaly or secondary hypothyroidism. However, pituitary lesions can induce complex clinical pictures due to alterations of different endocrine axes controlled by pituitary itself. A further rationale for studying CoQ10 in pituitary-adrenal diseases is related to the common biosynthetic pathway of cholesterol and ubiquinone. We have therefore assayed plasma CoQ10 levels in different conditions with increased or defective activity of pituitary-adrenal axis (3 subjects with ACTH-dependent adrenal hyperplasia, 2 cases of Cushing's disease and 1 case of 17-alpha-hydroxylase deficiency; 10 subjects with secondary hypoadrenalism, including three subjects with also secondary hypothyroidism). CoQ10 levels were significantly lower in isolated hypoadrenalism than in patients with adrenal hyperplasia and multiple pituitary deficiencies (mean +/- SEM: 0.57 +/- 0.04 vs 1.08 +/- 0.08 and 1.10 +/- 0.11 microg/ml, respectively); when corrected for cholesterol levels, the same trend was observed, but did not reach statistical significance. These preliminary data indicate that secretion of adrenal hormones is in some way related to CoQ10 levels, both in augmented and reduced conditions. However, since thyroid hormones have an important role in modulating CoQ10 levels and metabolism, when coexistent, thyroid deficiency seems to play a prevalent role in comparison with adrenal deficiency.

Relationships between plasma CoQ10 levels and thyroid hormones in chronic obstructive pulmonary disease.

In previous works we demonstrated an inverse correlation between plasma Coenzyme Q 10 (CoQ10) and thyroid hormones; in fact, CoQ10 levels in hyperthyroid patients were found among the lowest detected in human diseases. On the contrary, CoQ10 is elevated in hypothyroid subjects, also in subclinical conditions, suggesting the usefulness of this index in assessing metabolic status in thyroid disorders. On the other hand, a low-T3 syndrome, due to reduced peripheral conversion from the prohormone T4, is observed in different chronic diseases: this condition is considered an adaptation mechanism, usually not to be corrected by replacement therapy. In order to perform a metabolic evaluation, we have studied a group of 15 patients, aged 69-82 ys, affected by chronic obstructive pulmonary disease (COPD), comparing respiratory indexes, thyroid hormones and CoQ10 levels (also normalized with cholesterol levels) in patients with low (group A) or normal (group B) free-T3 (FT3) concentrations. We found that CoQ10 levels were significantly higher in patients of group A than in B (0.91+/- 0.03 vs 0.7 +/- 0.04 microg/ml respectively); the same difference was observed when comparing the ratios between CoQ10/cholesterol in the two groups (200.16 +/- 8.96 vs 161.08 +/- 7.03 nmol/mmol respectively). These preliminary data seem to indicate that low T3 levels are accompanied by metabolic indexes of a true hypothyroidism in COPD patients. Whether this datum supports the need to perform a replacement therapy in such a condition requires further studies.

Effect of UV-C mediated oxidative stress in leukemia cell lines and its relation to ubiquinone content.

UV-C radiation is able to impair cellular functions by directly damaging DNA, and by inducing an increased formation of reactive oxygen species that leads to a condition of oxidative stress. In this study we evaluated different responses to UV insult of two leukemia cell lines, HL-60 and Raji, and the relationship with their CoQ10 content. DNA damage was monitored by means of the alkaline single cell gel electrophoresis (Comet assay); intracellular levels of ROS, mitochondrial depolarization and cell viability was measured by flow cytometry. Raji cells appeared more resistant to the UV insult; moreover, they did not show any increase in ROS content and the extent of mitochondrial depolarisation was much lower than in HL 60 cell line. Raji cells also contained significantly higher levels of CoQ10 and their ability to incorporate and to reduce exogenous CoQ10 added to the culture medium was remarkably elevated compared with HL 60.

Coenzyme Q10, antioxidant status and ApoE isoforms.

The aim of this study was to inquire the antioxidant status in plasma and lipoproteins isolated from normal subjects possessing different ApoE genotypes. For this purpose we investigated blood samples from 106 healthy blood donors: the distribution of ApoE alleles (E2/E2 = 0.9%, E2/E3 = 10.4%, E2/E4 = 2.8%, E3/E3 = 71.7%, E3/E4 = 12.3% and E4/E4 1.9% with 1, 11, 3, 76, 13, and 2 subjects respectively for each genotype) was in agreement with previous data. Almost no differences were found in the concentrations of both coenzyme Q10 (CoQ10) and vitamin E for the different genotypes. Concentration of CoQ10 in isolated lipoproteins was also similar, in the different genotypes, when referred to cholesterol; CoQ10 in LDL was higher for the E3/E3 subjects when referred to protein. Neither CoQ10 nor vitamin E correlated with paraoxonase (PON) activity or cholesteryl-ester hydroperoxides (CHP). Furthermore, there was no correlation between the same lipophilic antioxidants and CHP levels. The only E2 homozygous subject found had high levels of PON and low levels of CHP; the two E4/E4 subjects had low PON activity together with low levels of CHP.

Hyperthermic antiblastic perfusion with TNFalpha and melphalan in stage III limb melanoma patients: A phase I - II SITILO study.

Hyperthermic antiblastic perfusion (HAP) has been proven to be an effective treatment of loco-regional spreading limb melanoma. The mean complete response (CR) rate obtained is 54%, with an objective responses (OR) rate ranging between 70% and 100%. Recently, Tumor Necrosis Factor (TNFalpha) has been employed at high dosages (3-4 mg) in association to Melphalan and hyperthermia. This trimodality combination increased the percentage of CR (70%-90%), but systemic toxicity was also reported due to high TNF doses. A phase I - II study was undertaken in order to assess the MTD of TNFalpha in association to true hyperthermia (41.5 degrees C) and Melphalan. Twenty patients affected with stages IIIA (9 patients), IIIAB (10 patients), and IV (1 patient) were enrolled in this study. The trimodality treatment did not increase the local and systemic toxicity. CR was observed in 70% of the patients, PR in 20% with on OR rate of 90%. These figures are overlapping those obtained with high TNF dosages. No correlation was observed between tumor responses and TNF doses. Taking into account that 70% of our patients have been treated with TNF dosages between 0.5 mg on 1.6 mg, we conclude that 1 mg is the best dosage to be applied during HAP. Patients with bulky tumor are the best candidate to TNF perfusion, because no differences have been observed in terms of CR in patients with low tumor burden treated with TNF-Melphalan-hyperthermia or Melphalan-hyperthermia.

[Clinical pathways and case management in anesthesiology]. / Le Clinical Pathways ed il Case Management in anestesiologia.

Clinical Pathways and the Case Management represent clinical and management tools for organizing patient care. These tools focus on results and use a multi-disciplinary approach, with the goal of providing high quality, cost effective care. Both systems require the care providers to interact with the institution or the health care network. As health care is part of a refund system, the specialist must cooperate with personnel of other disciplines as a member of a team which works together to improve the quality of health care, while containing the costs. The Clinical Pathways and the Case Management are two tools for achieving these goals. The most important limit of a cost control system is the division split of health care into single components instead of considering the entire diagnostic course. Without doubt, the Disease Management appears to be the most effective control system of health care costs now available.

Treatment of peritoneal carcinomatosis with intent to cure.

BACKGROUND AND OBJECTIVES: Low-grade malignant tumors arise in the abdomen, do not infiltrate, and "redistribute" on the peritoneum with no extraregional spreading. In these cases, aggressive surgery combined with localized chemotherapy may provide cure. METHODS: After removing the tumor with the regional peritoneum en bloc, intraabdominal hyperthermic chemoperfusion was performed throughout the abdominopelvic cavity. Alternatively, early intraabdominal chemotherapy, starting on the first postoperative day, was administered for 5 days. RESULTS: Forty patients affected with extensive peritoneal carcinomatosis underwent peritonectomy, with no residual macroscopic disease except in four cases. Seventy-five percent of the patients underwent locoregional chemotherapy. Major complications were observed in 40% of the patients and led to death in five; there was a direct correlation to the duration of surgery (P = 0.03). At a mean follow-up of 20 months, the overall 2-year survival was 61.4%, with a median survival of 30 months. CONCLUSIONS: After a learning curve of 18 months, the feasibility of the integrated treatment increased to greater than 90%, and mortality dramatically decreased. The combined treatment resulted in a high survival rate in patients with extensive carcinomatosis who were no longer responsive to traditional therapies.

[Echographic and sonographic study of ovaries in girls with precocious puberty]. / Studio ecografico e flussimetrico delle ovaie in bambine con pubertà precoce.

The aim of this study is the biometrical and morphological evaluation of the ovaries by sonography and the study of the haemodynamics of the ovarian artery flow by doppler ultrasound in 14 girls with precocious puberty and in 33 control subjects. All people ranged in age from 5 to 7 years. The gonadian mean volume and the mean pulsatility index have been evaluated. A significant difference in the ovarian volume has been found between patients and controls. No index between the two groups. We conclude that the doppler ultrasound needs a larger number of cases to evaluate its validity in girls with precocious puberty.

[Comparison of the use of classic diazoanalgesia in surgery and an applicative variant with buprenorphine]. / Confronto sull'uso in chirurgia della diazoanalgesia classica e di una variante applicativa con buprenorfina.

The authors have compared two different techniques of anaesthesia: the classical anaesthesia with benzodiazepine-analgesic (diazepam and fentanyl) and one of its variant obtained by using flunitrazepam and buprenorphine. The 45 patients submitted to gynaecological surgery were causally divided in two groups in connection with the two different anaesthesiological techniques. The clinical and statistical analysis of the collected data demonstrated the real validity of this anaesthesiological variant: either for premedication by perfect anxiolysis and sedation, or for the maintenance by low incidence on cardiocirculation system and perfect analgesia that extended its effects for many hours after surgical operation.