311 research outputs found
Secondary Hyperparathyroidism and Hypertension: An Intriguing Couple
No full text: Secondary hyperparathyroidism (SHPTH) is a major complication in patients on maintenance hemodialysis burdened with high cardiovascular risk. Hypertension is also a high prevalence complication contributing to an increase in the mortality rate in hemodialysis patients. A possible association between SHPTH and hypertension has been widely reported in the literature and several pathogenetic mechanisms have been described. There is evidence that the decrease of plasma iPTH levels are correlated with hypertension correction in hemodialysis patients undergoing parathyroidectomy and oral calcimimetics administration. We have observed a similar behaviour also in a patient on chronic hemodialysis treated with Etelcalcetide. Even if this is an isolated observation, it could stimulate future investigation, possibly in dedicated clinical trials
Homocysteine and Hydrogen Sulfide, Two Opposing Aspects in the Pathobiology of Sulfur Compounds in Chronic Renal Failure
No full textSulfur is an element with a plurality of functions, resulting from its numerous oxidation states in which it exists, which gives the emerging compounds a greatly diverse stability. Among these we have homocysteine, an amino acid, and hydrogen sulfide, an inorganic gas, both present in the human body, the former in increased amounts in chronic kidney disease, the latter is instead decreased.1,2 These compounds epitomize two opposites: homocysteine even if not incorporated into proteins, nonetheless binds to them strongly, while hydrogen sulfide is volatile
Clinical research and prevention: Fundamental elements of sustainable health care systems based on patients' needs
No full textProblems in health care systems are present on a planetary scale due to a discrepancy between scarce resources and vast needs. These are mainly generated by the aging of the population. Everywhere in the world, state health care agencies simply reduce the quantity and eventually the quality of available services. This approach is unacceptable, at least in Europe, where health care is a legal right, granted from birth to death. This paper departs from the poor support available nowadays for clinical research and the trivial investments on prevention, and hypothesizes a new approach based on clinical research and prevention which, in the long term, would generate a just, efficient, sustainable health care system stemming from patients' needs. This is discussed from various viewpoints. It emerges that there is a need to switch the focus of health systems away from cures towards prevention and as well as a need for better translational research. It is of note that in France such a program based on clinical research and prevention was launched in 2008.Problems in health care systems are present on a planetary scale due to a discrepancy between scarce resources and vast needs. These are mainly generated by the aging of the population. Everywhere in the world, state health care agencies simply reduce the quantity and eventually the quality of available services. This approach is unacceptable, at least in Europe, where health care is a legal right, granted from birth to death. This paper departs from the poor support available nowadays for clinical research and the trivial investments on prevention, and hypothesizes a new approach based on clinical research and prevention which, in the long term, would generate a just, efficient, sustainable health care system stemming from patients' needs. This is discussed from various viewpoints. It emerges that there is a need to switch the focus of health systems away from cures towards prevention and as well as a need for better translational research. It is of note that in France such a program based on clinical research and prevention was launched in 2008
Effects of verapamil on the abnormalities in fatty acid oxidation of myocardium
No full textEffects of verapamil on the abnormalities in fatty acid oxidation of myocardium. The oxidation of long (LCFA) and short chain fatty acids (SCFA) by myocardial mitochondria is impaired in CRF due to reduced activity of carnitine palmitoyl transferase (CPT) and of enzymes in the β-oxidation sequence in mitochondrial matrix. It was proposed that PTH, through its ability to augment entry of calcium into cells, enhances calcium uptake by the myocardium leading to calcium accumulation which in turn affects mitochondrial function. A calcium channel blocker may therefore correct these derangements. The present study examined the effects of verapamil on LCFA and SCFA oxidation and on CPT activity of myocardial mitochondria and on 45Ca uptake by, and calcium content of, myocardium obtained from CRF rats and rats treated with PTH, with and without administration of verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P < 0.01) reduction in the oxidation of LCFA and SCFA by and of CPT activity of myocardial mitochondria and a significant increase in 45Ca uptake by, and content of, the myocardium. Simultaneous administration of verapamil reversed all these derangements. Administration of verapamil alone to normal rats for 4 or 21 days did not cause significant changes in these parameters. The results of our studies are consistent with the notion that the alterations in myocardial oxidation of LCFA and SCFA in CRF or after PTH treatment are related to PTH-induced calcium accumulation in the heart, and could be reversed by a calcium channel blocker. The data could provide a rational therapeutic approach for the management of uremic myocardi-opathy
Verapamil reverses PTH- or CRF-induced abnormal fatty acids oxidation in muscle
No full textVerapamil reverses PTH- or CRF-induced abnormal fatty acids oxidation in muscle. Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and 45Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P < 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P < 0.01) increment in 45Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker
Phosphate depletion impairs insulin secretion by pancreatic islets
No full textPhosphate depletion impairs insulin secretion by pancreatic islets.Phosphate depletion (PD) is associated with resistance to the peripheral action of insulin and with glucose intolerance. However, data on the effect of PD on insulin secretion are not consistent, and were derived indirectly by measurements of blood levels of insulin during intravenous glucose tolerance test (IVGTT) or with hyperglycemic clamp technique. Direct evidence for an effect of PD on insulin secretion by pancreatic islets is not available, and the potential mechanisms through which PD may affect insulin secretion are not known. We performed IVGTT, examined in vitro insulin secretion by pancreatic islets, and evaluated various factors involved in insulin secretion in PD and pair weighed (PW) rats. PD animals had fasting hyperglycemia and normal plasma insulin levels, and displayed abnormal IVGTT as compared to PW rats. Both initial and late phases of D-glucose-induced insulin secretion from islets were markedly and significantly (P <0.01) lower than from islets of PW rats. In contrast, D-glyceraldehyde-induced insulin release in PD rats was similar to that of PW rats. [H3]2-deoxyglucose uptake by islets and their cyclic AMP content after exposure to D-glucose, D-glyceraldehyde or forskolin were not different among the two groups of animals. Insulin content in PD islets was modestly but significantly (P < 0.01) higher than PW islets. In PD islets, ATP content and the ATP/ADP ratio at basal state and after incubation with 16.7mm D-glucose were significantly (P < 0.01) lower and resting cytosolic calcium was significantly (P < 0.01) higher than in PW islets. Lactic acid output by islets from PD rats was significantly (P < 0.01) less than that from islets of PW rats. The data show that: 1) PD rats have glucose intolerance and marked reduction in insulin secretion; 2) resting cytosolic calcium of pancreatic islets of PD rats is elevated; 3) the defect in insulin secretion is not due to abnormal glucose uptake or cAMP production by or insulin content of the islets but due to a reduced ATP content, elevated resting cytosolic calcium and/or defective glucose metabolism by the islets. This latter defect is most likely due to reduced ATP content which is required for phosphorylation of glucose to fructose bisphosphate. 4) The decrease in ATP content of islets is most likely due to both PD per se and the associated high resting cytosolic calcium, since chronic rise in the latter is known to inhibit ATP production
FraRe: a net between the two sides of the Adriatic sea
No full textThe paper describes the web-site FraRe (http://studiumanistici.unimc.it/it/ricerca/progetti-di-ricerca-finanziati/frare/mappe-schede/mappa-frare) and its possibilities of expansion eastwards, to the the regions connected to the eastern shore of the Adriatic sea, since Franciscan settlements are very numerous in the whole Adriatica region. As far as the Marches are concerned, the web-site is already accessible on web; the user can localize the single Franciscan settlements on a Google map and can make queries concerning the chronology and the various grouping of conventsaccording to different categories (male/female, Observant/Conventual, and so forth). By connecting to the site FraRe from different kinds of devices, it’s possible to both visualize and create historical, religious and artistic virtual tours between convents and towns, and finally to organize a real journey. The data on the map could be uploaded in Google Earth and in Google Gallery and so the possibility to find the map and extract the information would be greater even for occasional users and tourists looking for more detailed notes about a geographical area, a convent, or a town.Since the settlements of the Friars Minor and of the Poor Clares cover many regions, on both sides of the Adriatic Sea, and had relationships between them, mapping the sites will allow to enlighten relationshipsbetween different areas, in Italy and in the Balkan territories,until the whole XVI-XVII century
The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin
No full textLanthionine is a nonproteinogenic amino acid, composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage. It is biosynthesized from the condensation of two cysteine molecules, while the related compound homolanthionine is formed from the condensation of two homocysteine molecules. The reactions can be carried out by either cystathionine-β-synthase (CBS) or cystathionine-γ-lyase (CSE) independently, in the alternate reactions of the transsulfuration pathway devoted to hydrogen sulfide biosynthesis. Low plasma total hydrogen sulfide levels, probably due to reduced CSE expression, are present in uremia, while homolanthionine and lanthionine accumulate in blood, the latter several fold. Uremic patients display a derangement of sulfur amino acid metabolism with a high prevalence of hyperhomocysteinemia. Uremia is associated with a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity, due to the accumulation of retention products. Lanthionine inhibits hydrogen sulfide production in hepatoma cells, possibly through CBS inhibition, thus providing some basis for the biochemical mechanism, which may significantly contribute to alterations of metabolism sulfur compounds in these subjects (e.g., high homocysteine and low hydrogen sulfide). We therefore suggest that lanthionine is a novel uremic toxin
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