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Biomedical subjects

G De Luca

Publications and source records attributed to G De Luca.

At least 127 records · Page 7Linked to original sources

The levels of adenine nucleotides and pyridine coenzymes in red blood cells from the newborn, determined simultaneously by HPLC.

The concentrations of ATP, ADP, AMP; NADP and NADPH; NAD and NADH were determined in erythrocytes from healthy newborns and compared with those obtained in healthy adults. No significant differences were found for the adenine nucleotide concentrations, but NADH levels were reduced in newborn erythrocytes, with a consequent increase in the NAD/NADH ratio. Moreover, in newborn erythrocytes increased levels of NADP were observed, with a consequent increase in the NADP/NADPH ratio and a decrease in the NAD/NADP ratio. These results indicate the need to use reference values of the ratios NAD/NADH, NADP/NADPH and NAD/NADP from healthy newborns in the study of syndromes affecting the metabolism of erythrocytes in the newborn.

Adenine Nucleotides↗

Structural and functional modifications of human aorta proteoglycans in atherosclerosis.

Proteoglycans (PGs) were extracted from minced normal human aorta intima and media and adjacent atherosclerotic plaques. Samples obtained from each individual artery which showed different degrees of atherosclerotic involvement were studied separately. Comparing normal and atherosclerotic areas from the same aorta, the hexuronic acid content was always lower in the atherosclerotic minces. Atherosclerotic samples always contained a higher percentage amount of chondroitinase AC resistant material. PGs were sequentially extracted with increasing guanidine hydrochloride (GuHCl) concentrations. 0.4 M GuHCl extracted about 13% of total PGs, containing mostly chondroitin sulphate (CS), whilst 4 M GuHCl extracted about 50% of total PGs, containing CS, dermatan sulphate (DS), heparan sulphate and hyaluronic acid. PGs from atherosclerotic minces showed a higher DS amount, based on electrophoretic glycosaminoglycan (GAG) analysis. PGs extracted with 4 M GuHCl were further characterized by gel-chromatography and by CsCl density gradient centrifugation. The relative content of PGs with highest hydrodynamic size appeared to be markedly reduced in all the atherosclerotic samples. LDL/GAGs and LDL/PGs interactions were studied by affinity chromatography. GAGs obtained by papain digestion of PGs extracted from atherosclerotic areas contained a glycosaminoglycuronan interacting more strongly with human LDL than GAGs from normal areas of the same artery. The complete elution of PGs required higher NaCl concentration than GAGs. Moreover, PGs from atherosclerotic samples showed higher affinity for LDL than PGs from normal areas of the same aorta.

Aged↗

Antihypertensive activity of indolepyruvic acid: a keto analogue of tryptophan.

We studied the effect of indole-3-pyruvic acid (IPA) on systolic blood pressure of normotensive, spontaneously hypertensive, DOCA + salt hypertensive, and Grollman hypertensive rats. Experiments were also carried out in order to investigate whether IPA may influence the development of hypertension in spontaneously hypertensive rats. Age-matched normotensive, spontaneously hypertensive, DOCA + salt hypertensive, and Grollman hypertensive rats treated with N-methylglucamine, were used as controls. Acute oral (up to 50 mg/kg) and intravenous (5 mg/kg) administration of IPA did not change systolic blood pressure in any models of hypertension. By contrast, a repeated administration of IPA (100 mg/kg/day, by oral gavage for 10 days) significantly decreased systolic blood pressure in all models of hypertension, while it elicited no significant effect in normotensive rats. Moreover, when IPA was given daily to 5-week-old spontaneously hypertensive rats for 7 weeks, it partially inhibited the development of hypertension. In addition, chronic administration of IPA caused enhanced levels of tryptophan and 5-hydroxyindoleacetic acid in the cortex and diencephalon. Brainstem serotonin content in both normotensive and spontaneously hypertensive rats was also enhanced by IPA treatment. Our results suggest that IPA lowers blood pressure in different rat models of hypertension and this effect seems to be correlated with an increase in cerebral serotonin metabolism.

Animals↗

Keratan sulphate: a functional substitute for chondroitin sulphate in O2 deficient tissues?

Keratan sulphate and chondroitin sulphate can each fill space and exert swelling pressure in collagenous fibrillar matrices, but whereas the former is synthesised from glucose precursor without consuming NAD, the latter converts 2 mols of NAD for each uronate residue in the polymer chain. We suggest that the observed distribution of keratan sulphate and chondroitin sulphate in cartilage, cornea and intervertebral disc are determined by the ambient oxygen tension, and that keratan sulphate is preferentially synthesised in conditions of oxygen lack. The implications of this hypothesis in the physiology of contact lenses, cartilage degeneration, corneal scar repair and ageing are discussed.

Aging↗

[Appendico-cecal invagination (considerations on a case)].

Taking as their starting point the observation of an isolated case of appendicocecal invagination in a homogeneous series of 4,200 appendicectomies observed, the authors take the opportunity of addressing in some detail the many aspects of the problem posed by this rare condition. With the aid of a review of the literature, an attempt is made to define and explain the aetiology, pathogenesis and classification of such forms. The authors review the various clinical criteria and instrumental aids available for reaching a correct diagnosis, assessing their respective virtues and defects, especially as regards the radiological, ultrasonographic and endoscopic investigations used; they come to the conclusion that none of these is in itself specific for this condition, and stress that a clinical suspicion of appendicocecal invagination can only emerge of the basis of an overall assessment of the various test findings in conjunction with actual clinical experience. Lastly, the authors review the therapeutic possibilities and conclude that surgical therapy, which varies from case to case, is the most reliable approach, in that the endoscopic therapy attempted by some cassies an excessively high degree of risk.

Adult↗

Pseudoxanthoma elasticum (PXE): ultrastructural and biochemical study on proteoglycan and proteoglycan-associated material produced by skin fibroblasts in vitro.

Pseudoxanthoma elasticum is a genetic disease characterized by progressive mineralization of elastic fibers. Previous studies suggested that other components, apart from elastin, might be involved in the alterations of this connective tissue disorder (Martinez-Hernandez and Huffer, 1974; Pasquali Ronchetti et al., 1981; 1986). Evidence is presented that proteoglycan metabolism is altered in PXE-affected patient. Urinary GAGs suggests an increased degradation of glucosamine-containing GAGs in the patient. Pulse and chase experiments on in vitro skin fibroblasts indicated a decreased rate of synthesis of [35SO4] containing GAGs or an increase of their turnover rate in PXE. Moreover, when PGs produced from skin fibroblasts were identified by ultracentrifugation and gel filtration in associative conditions, PXE fibroblasts produced a significantly higher amount of the high molecular weight fraction of sulfated PGs. This high molecular weight material was present both in the medium and in the matrix and disappeared under dissociative conditions or after treatment with hyaluronidase or with pancreas elastase. By electron microscopy, PXE fibroblasts appeared to produce and secrete an enormous amount of toluidine blue 0 positive material organized as filaments and amorphous masses. These data are in agreement with previous observations of the presence of abnormal masses of microfilaments, in the dermis of PXE patients, which were sensitive to hyaluronidase and partially to trypsin and elastase (Pasquali Ronchetti et al., 1986). The results seem to confirm that at least some of the alterations of connective tissues in PXE are due to abnormal PGs metabolism and to their tendency to form abnormal aggregates in the extracellular space.

Adult↗

Glucocorticoid regulation of spermidine acetylation in the rat brain.

The effect of glucocorticoids on polyamine metabolism has been elucidated further by measuring putrescine, spermidine, and spermine levels as well as ornithine decarboxylase, S-adenosylmethionine decarboxylase, and N1-acetylspermidine transferase activities in the hippocampus, cerebellar cortex, vermis, and deep nuclei of adrenalectomized rats. At 6 h after corticosterone or dexamethasone administration, the specific activities of ornithine decarboxylase and N1-acetylspermidine transferase showed the greatest increases in all brain tissues examined, and at 12 h, S-adenosylmethionine decarboxylase activity was not increased significantly. The hippocampus and cerebellar regions displayed different responses to corticosterone and dexamethasone, corresponding to the distribution of glucocorticoid and mineralocorticoid receptors. Corticosterone and dexamethasone increased ornithine decarboxylase and N1-acetylspermidine transferase activities in a dose-dependent manner, with dexamethasone being more active than corticosterone in all tissues. However, estradiol, progesterone, testosterone, and aldosterone were only active at doses greater than 5 mg/kg. The great increases in ornithine decarboxylase and N1-acetylspermidine transferase activities were accompanied by a marked increase in putrescine level and a small decrease in spermidine level. Our data confirm that the hippocampus and cerebellum are glucocorticoid target tissues and suggest that the increase in the content of putrescine, following acute treatment with glucocorticoids, is dependent on ornithine decarboxylase as well as N1-acetylspermidine transferase induction.

Acetylation↗

Liver replacement with reduced size donor organs.

End stage liver disease in children can be treated with orthotopic liver transplantation (OLT). Nevertheless, the expansion of this therapy in Europe has been limited because of the shortage of appropriate size-matched donors. One possible technical solution is the OLT of a liver graft previously reduced in size by in situ resection preceding the harvesting procedure. To study the impact of this technique we examined two different operative procedures performed on Landrace pigs. Group 1 consisted of 20 standard donor/recipient weight matched OLT. In group 2, 15 OLT were performed using right lateral and medial lobes (55% of the original donor liver). The donor/recipient weight ratio in the group was 2:1. Cold ischemia times were 90 +/- 16 min for group 1 and 98 +/- 9 min for group 2. It is emphasized that in contrast to all the other reports using resected liver grafts for OLT, the donor resection in our study was always performed in situ under normothermic conditions, preceding the harvesting procedure. This was designed to reduce the cold ischemia time. No significant technical problems were encountered. The biochemical results of group 2 pigs compared to group 1 demonstrate an analogous, postoperative course. This might be explained by regenerative stimuli acting on the resected liver tissues and enhancing their metabolic function. These data support the conclusion that resected adult donor liver grafts may be used for pediatric transplant recipients.

Animals↗

Comparison of combined portal-arterial versus portal perfusion during liver procurement.

PAP of harvested livers is routinely used to minimize parenchymal anoxia during storage. PP is compared with PAP to evaluate the relative reliability of PAP. Sixty female Landrace pigs were used for 30 OLTs. Group 1 livers underwent PP, whereas group 2 livers were treated with PAP. The cold ischemic time was less than 120 minutes for both groups, with no warm ischemia. Intraoperative and 24-hour postoperative biochemical, coagulation, and histocytological data were analyzed. Morphological studies of cellular damage were based on the percentage of CVD and KP and classified as light, moderate, and severe damage. Data, at closing, were compared by using Fisher's test (group 1 v group 2,P = 0.003 for light damage and P = .04 for severe damage; first postoperative day for group 1 v group 2, P = .133 for light damage and P = .25 for severe damage. Blood samples at closing and 24 hours postoperatively showed significant differences between groups 1 and 2: At closing for groups 1 and 2, respectively: AST, 968.9 +/- 742.7 and 327.4 +/- 174.7 IU/L (P less than .001); ALT, 63.1 +/- 40.3 and 20.3 +/- 5.3 IU/L (P less than .001); AP, 292.2 +/- 107.1 and 139.5 +/- 45.3 IU/L (P less than .001); and 24 hours postoperatively for groups 1 and 2, respectively: AST, 1,664.9 +/- 917.8 and 419.3 +/- 230.9 IU/L (P less than .001): ALT. 180.4 +/- 28.9 and 66.4 +/- 17.5 IU/L (P less than .001); AP, 602.1 +/- 153.3 and 255.7 +/- 116.3 IU/L (P less than .01). Comprehensively, the results reflect a better perfusate distribution of the PAP livers compared with PP ones: uniform organ preservation, faster metabolic recovery, and reduced postoperative mortality.

Animals↗

Collagen glycosylation in human granulation tissue and scar.

Some biochemical characteristics of collagen extracted from granulation tissue were studied and compared with those of normal skin and scar. By using electrophoretic techniques the type III collagen content was confirmed to be significantly greater in granulation tissue and lower in scar with respect to normal skin. The chromatographic determination of hydroxylysine (Hyl) glycosides in collagen extracted from granulation tissue showed a significant increase in both the degree of Hyl glycosylation and in the di-/monoglycoside ratio, while both parameters turned out to be lower in scar. These data suggest that the degree of Hyl glycosylation and the di-/monoglycoside ratio could represent an index of the degree of collagen fiber maturation.

Cicatrix↗

Therapy for advanced thyroid cancer: treatment of a high risk case.

The treatment of a high risk case of an advanced thyroid cancer is reported. The patient had a thyroid cancer with metastatic lesions of the frontal bone, left temporal bone, left sacroiliac joint, lytic destruction of C6 and lytic lesion of C7. A pre-operative immobilization of the cervical spine was performed by a halo cast set on a corset of gypsum. After this, the patient underwent a thyroidectomy and, at the same time, a metallic plate was applied to immobilize C5-C7. A month after he underwent reoperative surgery to stabilize definitively the cervical spine. Subsequently he was treated by TCT and 131I subdivided in several cycles. The latest total body scan demonstrated a complete regression of secondary lesions.

Adenocarcinoma↗

The effect of extracellular matrix modifications on UDP-glucose dehydrogenase activity in cultured human skin fibroblasts.

The effect of modifications of the extracellular matrix on the biosynthesis of glycosaminoglycans was investigated in human skin fibroblast cultures by studying UDPGDH activity in order to evaluate: a), the histoenzymological and biochemical modifications induced by chondroitinase ABC treatment (new experimental conditions were developed in order to obtain minimum cell damage); b), the reversibility of these modifications; c), the effect of growing the cells in the presence of chondroitinsulfate; d), the specificity of the modifications induced. The results demonstrated that our experimental conditions specifically affected intracellular UDPGDH activity. Chondroitinase ABC treatment induced a reversible increase of UDP-glucuronic acid synthesis. On the contrary, the presence of chondroitinsulfate in the growth medium completely inhibited UDPGDH activity.

Carbohydrate Dehydrogenases↗

Synthetic peptides related to the N-terminal amino acid sequence of a pharmacologically active decapeptide isolated from Crotalus atrox snake venom.

Synthesis is described of some peptides and peptide derivatives related to the N-terminal amino acid sequence of a pharmacologically active decapeptide (POL-236) recently isolated from Crotalus Atrox snake venom. The synthetic compounds were tested for hypotensive activity in anaesthetized normotensive rats. At the used doses all compounds failed to show the immediate hypotensive effect noted after POL-236 administration.

Amino Acid Sequence↗