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Biomedical subjects

F De Lorenzo

Publications and source records attributed to F De Lorenzo.

At least 37 records · Page 2Linked to original sources

Phosphate diabetes in patients with chronic fatigue syndrome.

Phosphate depletion is associated with neuromuscular dysfunction due to changes in mitochondrial respiration that result in a defect of intracellular oxidative metabolism. Phosphate diabetes causes phosphate depletion due to abnormal renal re-absorption of phosphate be the proximal renal tubule. Most of the symptoms presented by patients with phosphate diabetes such as myalgia, fatigue and mild depression, are also common in patients with chronic fatigue syndrome, but this differential diagnosis has not been considered. We investigated the possible association between chronic fatigue syndrome and phosphate diabetes in 87 patients who fulfilled the criteria for chronic fatigue syndrome. Control subjects were 37 volunteers, who explicitly denied fatigue and chronic illness on a screening questionnaire. Re-absorption of phosphate by the proximal renal tubule, phosphate clearance and renal threshold phosphate concentration were the main outcome measures in both groups. Of the 87 patients with chronic fatigue syndrome, nine also fulfilled the diagnostic criteria for phosphate diabetes. In conclusion, we report a previously undefined relationship between chronic fatigue syndrome and phosphate diabetes. Phosphate diabetes should be considered in differential diagnosis with chronic fatigue syndrome; further studies are needed to investigate the incidence of phosphate diabetes in patients with chronic fatigue syndrome and the possible beneficial effect of vitamin D and oral phosphate supplements.

Adult↗

Central cooling effects in patients with hypercholesterolaemia.

1. A prospective study has been carried out, and 68 patients with hypercholesterolaemia have been investigated to study the effects of central cooling on serum lipid levels. 2. Central cooling was obtained by the exposure of the whole body to cold water. All patients were trained to gradually reduce the water temperature from 22 to 14 degrees C and to increase the time of exposure from 5 to 20 min over a period of 90 days. The 33 male and 35 female patients were aged between 40 and 60 years at entry with total cholesterol of 6.0 mmol/l or greater and low-density lipoprotein (LDL)-cholesterol of 4. 0 mmol/l or greater. Thyroid-stimulating hormone, free thyroxine (FT4), total T3, total cholesterol, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, triacylglycerols and total fat mass (determined by dual-energy X-ray absorptiometry scan) were obtained at baseline and after 3 months treatment with hydrotherapy. 3. Central cooling obtained by hydrotherapy results in a median fall in tympanic temperature from 0.2 degrees C (P<0.001) to 0.8 degrees C (P<0.001). We have observed in these patients a significant reduction in total cholesterol (-0.2 mmol/l, P=0.006) and LDL-cholesterol (-0.2 mmol/l, P=0.004). Serum FT4 level was higher than baseline results in 30 of these hypercholesterolaemic patients (15.5 pmol/l to 17.3 pmol/l) and there was no significant change in serum thyroid-stimulating hormone and total T3. 4. In conclusion, in our patients with hypercholesterolaemia we have observed a significant reduction of total cholesterol and LDL-cholesterol after body temperature regulation.

Adult↗

Association of overall adiposity rather than body mass index with lipids and procoagulant factors.

The association between obesity and risk of coronary artery disease is well established. The distribution of body fat was shown to be related to serum lipids and lipoproteins in a group of healthy men, but the association between body fat and haemostatic factors is less clear. The aim of the present study was to determine the association of overall adiposity (OVRAD, percent total fat mass contributing to body weight) and body mass index (BMI, weight/height2) with lipids and haemostatic factors in order to evaluate which of these was more associated with circulating procoagulant factors. The total fat mass was estimated by dual-energy X-ray absorptiometry (DEXA) and OVRAD computed for 28 male and 36 healthy female subjects, whose median age were 44.2 years and 48.4 years respectively. In addition, the BMI was computed for each of them from their weight and height measurements. Fasting samples were analysed for serum lipids (total, HDL- and LDL-cholesterol and triglyceride) and plasma fibrinogen, factor VII coagulant (FVII:C) activity, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities. The men and women had similar median BMI (23.9 kg/m2 and 23.1 kg/m2 respectively), but the median fat mass of women (19.6 kg) was higher than that of men (16.9 kg). Age, BMI and OVRAD exhibited statistically significant correlations with lipids and haemostatic factors in both men and women. However, when BMI was adjusted for age and OVRAD, the statistically significant associations were no longer apparent in men or women. In contrast, OVRAD adjusted for age and BMI still exhibited statistically significant associations with FVII:C activity (R = 0.38, p = 0.05), triglyceride (R = 0.51, p = 0.008), LDL-cholesterol (R = 0.45, p = 0.02) and HDL/Total cholesterol ratio (R = -0.63, p <0.001). It is concluded that OVRAD, a fat mass-based index, rather than BMI, a weight-height based index, is better associated with circulating coronary risk factors.

Adult↗

Pathogenesis and management of delayed orthostatic hypotension in patients with chronic fatigue syndrome.

The relationship between orthostatic hypotension and chronic fatigue syndrome (CFS) has been reported previously. To study the pathogenesis and management of delayed orthostatic hypotension in patients with CFS, a case comparison study with follow-up of 8 weeks has been designed. A group of 78 patients with CFS (mean age 40 years; 49% men and 51% women), who fulfilled the Centre for Disease Control and Prevention criteria were studied. There were 38 healthy controls (mean age 43 years; 47% men and 53% women). At entry to the study each subject underwent an upright tilt-table test, and clinical and laboratory evaluation. Patients with orthostatic hypotension were offered therapy with sodium chloride (1200 mg) in a sustained-release formulation for 3 weeks, prior to resubmission to the tilt-table testing, and clinical and laboratory evaluation. An abnormal response to upright tilt was observed in 22 of 78 patients with CFS. After sodium chloride therapy for 8 weeks, tilt-table testing was repeated on the 22 patients with an abnormal response at baseline. Of these 22 patients, 10 redeveloped orthostatic hypotension, while 11 did not show an abnormal response to the test and reported an improvement of CFS symptoms. However, those CFS patients who again developed an abnormal response to tilt-test had a significantly reduced plasma renin activity (0.79 pmol/ml per h) compared both with healthy controls (1.29 pmol/ml per h) and with those 11 chronic fatigue patients (1.0 pmol/ml per h) who improved after sodium chloride therapy (p = 0.04). In conclusion, in our study CFS patients who did not respond to sodium chloride therapy were found to have low plasma renin activity. In these patients an abnormal renin-angiotensin-aldosterone system could explain the pathogenesis of orthostatic hypotension and the abnormal response to treatment.

Adult↗

Possible relationship between chronic fatigue and postural tachycardia syndromes.

Postural tachycardia syndrome refers to the development of symptoms such as light-headedness, visual blurring, palpitations and weakness on assuming an upright posture; these symptoms are relieved by resuming a supine posture. This syndrome is occasionally associated with idiopathic hypovolemia, impaired vasomotor tone, deconditioning and autonomic neuropathy, but has not been reported in association with chronic fatigue syndrome (CFS). We describe five patients who satisfied the CFS criteria of the Centres for Disease Control and Prevention. Upright tilt-table testing induced significant hypotension and increased heart rate in all five patients, consistent with clinical and autonomic manifestation of postural tachycardia syndrome.

Adult↗

Extracoronary atherosclerosis and genetic variants of apolipoprotein AI-CIII cluster in myocardial infarction survivors from southern Italy.

The relationships between some genetic markers, as evaluated by DNA analysis, and ultrasound evidence of extracoronary athero-sclerosis, as detected by ultrasound methods, were evaluated in 39 myocardial infarction survivors of middle age and in 40 healthy controls of comparable age. Coronary heart disease (CHD) patients showed higher levels of triglycerides (P = 0.01) and greater number of exsmokers (P = 0.004). Carotid stenoses (> 15%) were detected in ten CHD patients and in two controls; iliac stenoses (> 15%) or abnormal ankle/arm ratio (< 0.97) were found in ten CHD patients and in one control; the scores of vascular disease severity in the myocardial infarction survivors were higher (Mann-Whitney test) than in controls (P < 0.01). Molecular genetic analysis of SstI restriction fragment length polymorphism (RFLP) of the apolipoprotein (apo) AI-CIII cluster and of the apo B gene demonstrated a higher frequency of the S2 allele (SstI RFLP) in coronary patients than in controls (P = 0.04) and no significant differences in the frequencies of XbaI RFLP of the apo B gene between patients and controls. The relative risk of myocardial infarction associated with an abnormal vascular score (> 8) or with the presence of the rare allele S2 (SstI apo AI-CIII polymorphism) was estimated by odds ratios. The lower 95% limits of odds ratios were above 1 (indicating significant increase in the relative risk of myocardial infarction) both in the case of vascular score and that of SstI RFLP. These associations were independent of one another and of triglyceride levels. SstI RFLP association with CHD disappeared after adjustment for smoking habits.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗

Alpha 2(I) collagen gene expression is up-regulated in quail chondrocytes pretreated with retinoic acid.

alpha 2(I) collagen gene expression is induced in quail embryo chondrocytes pretreated with retinoic acid (RA). The initial appearance of alpha 2(I) mRNA occurs around day 3 of culture in RA-free medium and rapidly progresses over the next 4 days. In transient transfection assays, expression of COL1A2-CAT, a chimeric gene bearing 3500 bp upstream the bone/tendon transcription start site from the human alpha 2(I) gene fused to the CAT gene, is stimulated severalfold in RA-treated chondrocytes. In contrast, enzyme activity is very low in untreated chondrocytes, suggesting that the sequences required for RA-induced transcription of the alpha 2(I) gene are present in this plasmid. Analysis of alpha 2(I) promoter sequences performed with deletion mutants gives overlapping results in collagen type I-producing fibroblasts and chondrocytes withdrawn from RA treatment. These experiments suggest that RA-induced transcription of the alpha 2(I) collagen gene in chondrocytes is regulated by the binding of transcription factors to the same regulatory sequences that control transcription in fibroblasts.

Animals↗

Coronary heart disease, echo-Doppler evidence of peripheral arterial disease and polymorphism of apolipoprotein B gene and Apo AI/CIII cluster.

The possible associations between coronary heart disease (CHD) and peripheral arterial disease (PAD), detected by echo-Doppler analysis, with restriction fragment length polymorphism (RFLP) of apo AI/CIII cluster and apo B gene were investigated in a group of men with premature CHD (n = 39) and in a control group of men without evidence of CHD (n = 40). The genetic analysis of SstI RFLP of apo AI/CIII cluster showed a significantly higher frequency of the rare SstI allele (S2) in CHD patients (0.16) as compared with controls (0.06). No significant differences were found in the frequencies of XbaI RFLP for the apo B gene between CHD patients and controls. Moreover, patients with PAD showed no significant differences in the frequencies of XbaI RFLP for the apo B gene and of SstI RFLP for the apo AI/CIII cluster as compared with patients without evidence of peripheral arterial disease detected by echo-Doppler analysis.

Alleles↗

XbaI polymorphism of the apolipoprotein B gene in patients with hyperlipidemia and echo-Doppler evidence of arterial lesions.

This study was designed to assess whether the XbaI restriction fragment length polymorphism (RFLP) for apolipoprotein B (apo B) gene could be related with a genetic predisposition to develop hyperlipidemia and atherosclerosis. Relationships between XbaI RFLP and serum cholesterol were evaluated by comparing hyperlipidemic patients with healthy controls. Statistical analysis (chi-square test) showed no significant difference in either genotype distribution or allele frequencies. Hyperlipidemic patients were then divided according to triglycerides, either above or below 200 mg/dl and XbaI genotype frequencies were measured. No significant differences in genotype distribution or allele frequencies were found. The hyperlipidemic patients were tested for the presence of arterial disease by echo-Doppler and angina questionnaire. The XbaI genotype frequencies were determined in patients with arterial disease and compared to those without evidence of disease. No significant differences were found between the two groups.

Adult↗

UN-1, a murine monoclonal antibody recognizing a human thymocyte undescribed antigen.

A monoclonal antibody (MoAb), UN-1, specific for a human thymocyte cell surface antigen was produced. The same MoAb recognized in immunofluorescence also cells of the human T line HPB-ALL, while did not bind human peripheral blood cells and cells of some T, B and myeloid lines. Western blotting analysis of thymocyte membranes with MoAb UN-1 revealed a structure with a molecular weight of 150 kDa. Therefore both the pattern of expression and the size of the antigen recognized by MoAb UN-1 did not correspond to any previously described cell surface molecule.

Animals↗

Spontaneous and mutagen-mediated amplification of a neo gene integrated at different genomic sites in rat 2 fibroblasts.

A promoterless neo gene was stably transfected in rodent fibroblasts to act as a reporter gene for rearrangements resulting in its expression at the different genomic integration sites. Nine clones were isolated which had integrated a varying copy number of neo at one or more genomic sites but still displayed a Neo- phenotype (G418-sensitive). These clones were analyzed for their ability to become Neo+ (G418-resistant) either spontaneously or after mutagen treatment. They were all able to generate G418-resistant subclones spontaneously at frequencies ranging from 2 x 10(-8) to 6 x 10(-5). The acquired G418-resistance was always associated with amplification and enhanced transcription of neo. No correlation was observed between the frequency of occurrence of G418-resistance and the number of copies or integration sites of neo. When treated with the mutagens mitomycin C or methylmethane sulfonate, only one clone, RH15, produced G418-resistant subclones in a dose-related fashion. In this mutagen-inducible clone, DNA lesions of a different nature (monoadducts or cross-links) were equally efficient in the induction of G418-resistance. Amplification and enhanced transcription of the neo gene were observed in both the spontaneous and mutagen-induced G418-resistant subclones of RH15 cell line. These findings indicate that the exogenous neo gene integrated at different genomic sites was acting as a reporter gene for amplification. Interestingly, while all nine integration sites were observed to amplify spontaneously, only one could be induced to amplify by mutagens. This suggests that different genomic regions display differing susceptibilities to mutagen-mediated amplification. This may be important in view of the major role played by mutagen-mediated gene amplification in carcinogenesis.

Animals↗

Expression of type X collagen is transiently stimulated in redifferentiating chondrocytes pretreated with retinoic acid.

Growth of quail chondrocytes in the presence of retinoic acid (RA) results in the suppression of the differentiated phenotype. RA-treated chondrocytes recover their differentiated phenotype if they are cultured for an additional 15 days in the absence of RA. A few days after removal from RA, treated chondrocytes acquire the polygonal morphology characteristic of chondrocytes growing as attached cells; they also gradually resume collagen II expression and synthesize cultures. The levels of collagen X mRNA decrease during the second week of culture in the absence of RA. Finally, at the end of 15 days, the absolute levels of collagen II and collagen X mRNAs are very similar in control and recovering chondrocytes.

Animals↗

Effect of enzyme inducers on metabolism of 1-nitropyrene in human hepatoma cell line HepG2.

We measured the response of HepG2 cells to the classic cytochrome (cyt.) P-450 inducers 3-methylcholanthrene (3-MC) and phenobarbital (PB), by evaluating oxidative and/or reductive metabolism of the nitroarenes, 1-NP and 1,6-dinitropyrene (1,6-DNP), in control and induced cells. In HepG2 cells, 3-MC induces ring-hydroxylation of 1-NP, whereas PB stimulates its nitroreduction. PB induces NADPH-cyt. c reductase, but does not affect other cytosolic and microsomal enzymes which contribute to 1-NP nitroreduction in these cells. However, PB-inducible nitroreductase activity seems to be associated primarily with cyt. P-450 isoenzymatic form(s), as indicated by the requirement for NADPH and the response to specific inhibitors such as alpha-naphthoflavone and CO.

Carcinoma, Hepatocellular↗