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Biomedical subjects

G Cozzi

Publications and source records attributed to G Cozzi.

At least 19 recordsLinked to original sources

Biochemical characterization of a recombinant von Willebrand factor (VWF) with combined type 2B and type 1 defects in the VWF gene in two patients with a type 2A phenotype of von Willebrand disease.

BACKGROUND: In a patient previously diagnosed with type 2A von Willebrand disease (VWD) [absence of high and intermediate molecular weight von Willebrand factor (VWF) multimers and markedly reduced ristocetin-induced platelet aggregation (RIPA)], an infusion test of desmopressin was followed by mild thrombocytopenia. This led to further laboratory investigations of his affected brother and of family members, who showed different phenotypic patterns compatible with type 1, 2A, 2B and an uncertain classification of VWD. The two brothers were compound heterozygotes (C275R/P1337L), whereas the others members of the family were heterozygous for C275R (a novel mutation in the D1 domain) or P1337L (a type 2B mutation in the A1 domain). OBJECTIVE AND METHODS: To evaluate the role of the combined effect of the two mutations in the two brothers, C275R and P1337L recombinant (r) VWFs were transiently expressed in COS-7 cells. RESULTS: Recombinant VWF levels secreted in cell media were similar for wild-type (WT), P1337L and hybrid P1337L/WT rVWFs, reduced for hybrids C275R/P1337L and C275R/WT rVWFs, and strongly reduced for C275R rVWF. All rVWFs had a full set of multimers except C275R rVWF, which had only dimers. P1337L rVWF and C275R/P1337L rVWF showed the highest degree of binding to glycoprotein (GP) Ibalpha and the lowest to collagen, followed by P1337L/WT rVWF (with an intermediate level of binding to both ligands), and by WT rVWF with the lowest level of binding to GPIbalpha and the highest to collagen. CONCLUSION: These results suggest that the two compound heterozygous patients have a circulating VWF mainly mutated in the A1 domain (P1337L). This peculiar type 2B VWF variant showed a remarkably high affinity for the GPIbalpha platelet receptor, leading to the loss of high and intermediate molecular weight multimers and hence to decreased RIPA, as in type 2A VWD.

Collagen↗

Effect of Lobesia botrana damages on black aspergilli rot and ochratoxin A content in grapes.

Sixty-nine wine grape samples of two varieties (Bombino Nero and Uva di Troia) were collected from four vineyards in a high ochratoxin A (OTA) incidence grape-growing area in Apulia, southern Italy, during the 2001 and 2002 crop harvests. The levels of toxin, measured in the two year harvests, ranged from 0.02 to 681 ng/g of fresh berries. In both surveys, higher levels of contamination by black aspergilli and OTA were found in both intact and rotten berries originating from bunches damaged by Lobesia botrana larvae as compared to bunches without L. botrana attacks. All berry samples with an OTA level >1 ng/g were contaminated by black aspergilli with a CFU>10(6), and all but one of these samples belonged to the Lobesia damaged berries group. This is the first evidence of an interaction between L. botrana damaged berries and OTA contamination, in field.

Animals↗

Transmembrane pressure modulation in high-volume mixed hemodiafiltration to optimize efficiency and minimize protein loss.

The aim of the present study was transmembrane pressure (TMP) modulation in high-volume mixed hemodiafiltration (HDF) to optimize efficiency and minimize protein loss. The optimal flow/pressure conditions in on-line mixed HDF assisted with a feedback control of TMP were defined in this prospective randomized study in order to obtain maximal efficiency in solute removal while minimizing potential side effects. Two different TMP profiles in mixed HDF were compared in 12 unselected patients who underwent two study periods of 2 weeks each in cross-over randomized sequence: (A) constant TMP at around 300 mmHg and (B) profiled TMP, in which TMP was slowly increased from a low initial value to the maximal value. In both procedures, the mean volume exchange was 10.6+/-1.4 l/h. Mean filtration fraction was 53%. Instantaneous beta2-microglobulin (beta2-m) clearance was higher at the start of the session with profiled TMP (207+/-35 vs 194+/-28 ml/min, P<0.005), whereas no differences were found at the end (135+/-19 vs 132+/-19 ml/min). Profiled TMP resulted in a higher mean beta2-m clearance of the session (97.0+/-15.4 vs 87.8+/-18.3 ml/min, P<0.01), in lower albumin loss in the first 30 min (0.62+/-0.14 vs 0.98+/-0.18 g, P<0.0001), and, in the whole session (3.98+/-1.19 vs 5.24+/-0.77 g, P<0.001), in higher dialyzer ultrafiltration coefficients and lower resistance indexes. This study showed that the TMP feedback modulation in mixed HDF was highly effective in maintaining very high ultrafiltration rates and filtration fractions, and minimized potential side effects as a result of the improved preservation of membrane permeability and more favorable dialyzer pressure regimen.

Aged↗

Expression studies on a novel type 2B variant of the von Willebrand factor gene (R1308L) characterized by defective collagen binding.

A novel mutation, R1308L (3923G > T) was present in the heterozygous state in five members of a family with type 2B von Willebrand disease (VWD) characterized by a full set of von Willebrand factor (VWF) multimers in plasma and by the absence of thrombocytopenia before and after desmopressin (DDAVP). The defect (R1308L) was located at the same amino acid position of one of the most common mutations associated with type 2B VWD (R1308C), which is characterized by the loss of high molecular weight VWF multimers (HMWM) in plasma and the occurrence of thrombocytopenia. To understand the mechanisms of this defect, the novel (R1308L) and 'common' (R1308C) mutations were expressed in COS-7 cells, either alone or, to mimic the patients' heterozygous state, together with wild-type VWF. R1308L recombinant VWF (rVWF) had a higher affinity for the platelet glycoprotein Ibalpha (GPIbalpha) receptor than wild-type rVWF, R1308C rVWF showing an even higher affinity. A novel finding was that both mutant rVWFs showed a similarly reduced binding to collagen type I and type III in comparison with wild-type rVWF. The latter finding suggests a more important role than recognized so far for the VWF A1 domain in VWF binding to collagen, which may contribute to the in vivo hemostatic defect associated with type 2B VWD.

Adult↗

Transhepatic contemporary palliation of biliary and duodenal stenoses by means of metallic stents.

We describe the treatment of a stenosing lesion of the horizontal duodenum by means of a large-bore metallic stent inserted percutaneously in a patient with transhepatic biliary drainage. In the same session, we used an expandable metallic stent in the biliary tree to relieve jaundice. We recommend the transhepatic approach for duodenal metallic stent insertion in patients with percutaneous biliary drainage.

Adenocarcinoma↗

Down-regulation of platelet-derived growth factor receptor signaling during myogenesis.

Cell differentiation is often associated with a block in the cell cycle. Growth factor signaling has been reported to be impaired in differentiated cells, due to the withdrawal of growth factors or to transcriptional down-regulation of their receptors. Our proposal is that the down regulation of growth factor signaling may be achieved through an alternative pathway: the decrease of growth factor receptor activation and the ensuing inhibition of intracellular pathways leading the cell to division. Here we report that platelet-derived growth factor receptor (PDGFr) signaling is down-regulated during muscle differentiation, although its expression level remains unchanged. PDGFr signaling inhibition is achieved through a decrease in the receptor tyrosine phosphorylation level, in particular of Tyr716, Tyr751, Tyr857 and Tyr1021, leading to down-regulation of intracellular signaling pathways. Furthermore, during myogenesis, the expression level of several phosphotyrosine phosphatases (PTPs) increases and most of them shift toward the reduced/activated state. We propose a causal link between the down-regulation of PDGFr tyrosine phosphorylation and the increases in PTP specific activity during myogenesis.

Animals↗

Long-term results of balloon dilation of benign bile duct strictures.

PURPOSE: To evaluate the results of percutaneous balloon dilation of benign bile duct strictures in a series of patients with a long follow-up period. MATERIAL AND METHODS: 56 patients with benign bile duct strictures underwent balloon catheter dilation. These patients had strictures of various origins: postsurgical, postlocal not surgical treatments, associated with gallstones, due to primary sclerosing cholangitis and to Mirizzi's syndrome. In 41 cases the diagnosis was made on the basis of radiological findings and history and in 15 cases on the basis of transluminal biopsy. RESULTS: In 87.5% of cases the treatment was immediately successful. There were no early recurrences, but 7 (21%) recurrences were seen over 1 year after treatment; of these, 57% underwent another balloon dilation procedure with a positive long-term outcome. CONCLUSION: The long-term success rate obtained in 72% of this series confirms that percutaneous bile duct dilation is a valid alternative to surgery without being burdened by complications; the procedure is also a valid alternative to the approach using endoscopic stents.

Adult↗

Portal biliopathy.

Herein we describe a case of obstructive jaundice and cholangitis originating from choledochal lithiasis secondary to a stricture of the common bile duct in a patient with cavernous transformation of the portal vein. In fact, portal cavernous transformation gives rise to many dilated pericholedochal and periportal collaterals that bypass the portal vein obstruction. Extrinsic compression of the common duct by dilated venous collaterals together with pericholedochal fibrosis from the inflammatory process causing portal thrombosis may lead to biliary stricture and dilatation of the proximal biliary tree. This condition sometimes causes the formation of secondary biliary stones and cholangitis. Treatment in our case could not be accomplished by a biliodigestive anastomosis because the patient suffered from a short bowel syndrome subsequent to extensive ileal resection for splanchnic venous thrombosis. We repeatedly attempted stone removal during endoscopic retrograde cholangiopancreatography (ERCP) but finally resorted to a percutaneous transhepatic approach, which permitted removal of the stones and treatment of the stricture by pneumatic dilatation. The patient remains well 3 years after the procedure and has shown no signs of jaundice or cholangitis.

Aged↗

Glucose or essential amino acid infusions in late pregnant and early lactating Simmenthal cows failed to induce a leptin response.

To assess the leptin response to metabolic challenges, three Italian Simmental cows were infused for 6 h: with (a) saline (control); (b) glucose; and (c) amino acid solutions according to a 3 x 3 Latin square experiment. The infusions were carried out at the 36th week of pregnancy, and the second and 12th week of the following lactation. At each of the three infusion periods, blood samples were collected from the jugular vein before and 15, 30, 120, 180, 240, 300 and 360 min after the beginning of each infusion. All samples were analysed for leptin, insulin, glucagon, growth hormone (GH), glucose, non-esterified fatty acids (NEFA) and urea. The physiological phase of the cows significantly affected the basal concentrations of insulin, glucagon, urea and NEFA. The infusion of both glucose and the amino acid solutions did not affect leptin concentrations. Insulin response was significantly increased when animals were infused with the glucose solution and, within treatment, the greatest response was observed at the 12th week of lactation. The greatest glucagon response was observed when infusing the amino acid solution. Urea response to all treatments increased from the dry period to the 12th week of lactation. The GH and NEFA responses were not affected by treatments. The Multi Species radio-immunoassay used in this study showed a lower sensitivity for ruminant leptin which may partially explain the lack of significant leptin variations. However, it can be hypothesized that leptin variations around parturition can be affected by the negative energy balance, and leptin release is not acutely affected by glucose and amino acid availability. In addition, no short-term relationship were found between insulin, glucagon and GH and leptin release in Italian Simmental cows during the dry period and early lactation.

Amino Acids, Essential↗

The provision of solid feeds to veal calves: I. Growth performance, forestomach development, and carcass and meat quality.

Growth performance, forestomach development, and carcass and meat quality of veal calves fed a milk replacer diet (Control) were compared to those obtained from calves fed the same liquid diet plus 250 g x calf(-1) x d(-1) of dried beet pulp or wheat straw. Three groups of 46 Polish Friesian calves, balanced according to initial BW, were assigned to the three dietary treatments in a fattening trial, which lasted 160 d. The provision of either solid feed did not affect the milk replacer intake. However, calves' ADG was increased (P < 0.01) only by feeding the beet pulp diet. The administration of both solid feeds improved calves' health status; calves fed solid feeds required fewer iron treatments for low hemoglobin and needed less medical treatments for respiratory or gastrointestinal diseases. In comparison to the Control calves, the provision of wheat straw and beet pulp increased iron intake throughout the fattening period by 41 and 130%, respectively. However, only calves fed beet pulp showed higher levels of hemoglobin and plasma iron concentrations (P < 0.05), whereas the same blood parameters were similar between Control calves and those fed wheat straw. At slaughter, both solid feeds led to empty forestomach weights heavier than those of Controls without reducing dressing percentage. The reticulorumen was heaviest in calves fed beet pulp, whereas wheat straw promoted omasal development. The administration of beet pulp resulted in a better carcass conformation than did the Control diet or wheat straw, but it had a detrimental effect on carcass color, which was graded as the darkest (P < 0.001). Consistent with this result, meat color of calves fed beet pulp was darker than that of Control calves and those fed wheat straw, because of the higher hematin concentration measured at the muscle level. No differences in carcass and meat color were observed between Control calves and calves fed wheat straw. The administration of solid feeds for welfare purposes does not always prevent the production of veal meat fulfilling the color standards required by the market. There is not a straight-forward relationship between a solid feed's iron content and the "redness" of veal meat, which should be related to the capability of the calves to use the iron provided by the roughage.

Animal Feed↗

The provision of solid feeds to veal calves: II. Behavior, physiology, and abomasal damage.

The aim of this study was to evaluate the effects of the addition of two roughage sources (wheat straw and beet pulp) to the milk replacer diet of veal calves, in order to reduce stress and improve animal welfare. We allocated 138 Polish Friesian male calves to three different feeding plans: a milk replacer diet (Control), 250 g/d of wheat straw in addition to the milk replacer, or 250 g/d of dried beet pulp in addition to the milk replacer. Within each feeding treatment, 16 calves were individually housed and 30 were kept in group pens (five calves/pen). Several behavioral, physiological, and health welfare indicators were monitored throughout the fattening period, which lasted for 160 d. Abnormal oral behavior around the meals was higher in Control calves (P < 0.01), while its lowest level was observed in straw-fed calves. At the beginning of the trial, chewing was higher in calves receiving solid feeds (P < 0.001), but the difference from the Control gradually decreased and disappeared at wk 13 for calves fed beet pulp and at wk 17 for those fed wheat straw. At the end of the fattening period, no differences among treatments were found in the frequency of chewing. Regardless of the diet, self-grooming decreased with age and no relationship was observed between this behavior and the presence of rumen hairballs. Cross-sucking was performed with low frequencies (from 4.70% at wk 2 to 1.05% at wk 23 around the meals, and even lower far from the meals) and was not affected by the provision of roughage. The time in contact with the bucket during the whole day was higher in Controls, whereas calves fed wheat straw maintained a lower level of this activity until the end of the trial (P < 0.01). The calves fed wheat straw spent more time in contact with the feed trough (P < 0.001) than those fed beet pulp and Control calves. No differences were found in cortisol curves due to the feeding treatment. In calves fed beet pulp, most hematological measures statistically differed from the other treatments, possibly in response to the higher iron intake and(or) to the higher hemoconcentration, probably due to the administration of beet pulp as dried feed. The incidence of abomasal ulcers and erosions was increased by the provision of the solid feeds, particularly by a structured fiber source such as straw. A roughage source able to satisfy calves' behavioral needs and to improve digestive processes without damaging the digestive apparatus still has to be identified.

Abomasum↗

The provision of drinking water to veal calves for welfare purposes.

Growth performance, behavior, physiology, forestomach development, abomasal lesions, and meat quality of veal calves fed a milk-replacer diet (No Water) were compared to those obtained from calves fed the same diet and provided with increasing amounts of drinking water (Water). Two groups of 69 Polish Friesian calves, balanced according to initial BW, were assigned to two water treatments in a 3 x 2 x 2 factorial arrangement that provided solid feed in addition to the milk-replacer diet (No solid feed, 250 g x calf(-1) x d(-1) of wheat straw or the same amount of beet pulp), and the adoption of two housing systems (individual stall vs group pen). The fattening trial lasted 160 d, and calves received drinking water starting from the 2nd wk of the study. The amount of drinking water was progressively increased from 3 to 8 L x cal(-1) x d(-1). Although not dehydrated, as shown by hematocrit and Na, K, and total protein hemoconcentration, calves consumed almost all the offered amount of water throughout the fattening period. Therefore, the water provided by the milk replacer alone, which ranged between 6 to 16 L calf d(-1), was not sufficient to satisfy the need of the animal. Drinking water did not affect the calves' growth performance but it reduced nonnutritive oral behavior throughout the fattening period. Based on these results, drinking water did not cover a shortage in the calves' water requirement but it played a role in environmental enrichment. Health status was similar between treatments, although water provision reduced the episodes of feed refusal. The measurement of chronic stress by ACTH challenge showed that the administration of drinking water would be advisable when calves are fed with small amounts of solid feed for well-being. Feces consistency and animal cleanliness were not affected by drinking water. At slaughter, forestomach development was similar between treatments, and drinking water did not affect the number of calves showing rumen hair-balls and abomasal lesions. No differences in color and other meat quality traits were observed between Water and No Water calves. Despite the lack of direct effects on productive traits, when water was available, the calves drank it, and positive effects were noticed on their nonnutritive oral behaviors and chronic stress indicators.

Adrenocorticotropic Hormone↗

Post-World War II uranium changes in dated Mont Blanc ice and snow.

Recent controversies concerning the possibility of environmental contamination due to the use of uranium in classical weaponry have led us to realize that there is a lack of time series for this metal from environmental archives. We have therefore performed analysis of a dated 140 m-long ice/snow core that was drilled in 1994 at a cold high altitude site (4250 m) near the summit of Mont Blanc in the French-Italian Alps. Ultraclean analytical procedures were employed in our analyses. Uranium concentrations were determined by inductively coupled plasma sector field mass spectrometry. In ice dating from before the 1940s, uranium concentrations are found to have remained fairly constant and can be explained simply by a crustal contribution. For the post-World War II layers, on the other hand, the data show large excesses above crustal contributions. These uranium excesses are attributed to tropospheric transport of dust emitted during extensive mining and milling operations which took place in the GDR and to a smaller extent in France at that time. There is no enhancement in uranium concentrations in the ice layer in which fallout from the 1986 Chernobyl accident was previously identified from a gross beta activity vs depth profile.

Altitude↗

Low molecular weight protein-tyrosine phosphatase is involved in growth inhibition during cell differentiation.

Low molecular weight protein-tyrosine phosphatase (LMW-PTP) is an enzyme involved in mitogenic signaling and cytoskeletal rearrangement after platelet-derived growth factor (PDGF) stimulation. Recently, we demonstrated that LMW-PTP is regulated by a redox mechanism involving the two cysteine residues of the catalytic site, which turn reversibly from reduced to oxidized state after PDGF stimulation. Since recent findings showed a decrease of intracellular reactive oxygen species in contact inhibited cells and a lower tyrosine phosphorylation level in dense cultures in comparison to sparse ones, we studied if the level of endogenous LMW-PTP is regulated by growth inhibition conditions, such as cell confluence and differentiation. Results show that both cell confluence and cell differentiation up-regulate LMW-PTP expression in C2C12 and PC12 cells. We demonstrate that during myogenesis LMW-PTP is regulated at translational level and that the protein accumulates at the plasma membrane. Furthermore, we showed that both myogenesis and cell-cell contact lead to a dramatic decrease of tyrosine phosphorylation level of PDGF receptor. In addition, we observed an increased association of the receptor with LMW-PTP during myogenesis. Herein, we demonstrate that myogenesis decreases the intracellular level of reactive oxygen species, as observed in dense cultures. As a consequence, LMW-PTP turns from oxidized to reduced form during muscle differentiation, increasing its activity in growth inhibition conditions such as differentiation. These data suggest that LMW-PTP plays a crucial role in physiological processes, which require cell growth arrest such as confluence and differentiation.

Animals↗

The influence of farmers' behavior on calves' reactions to transport and quality of veal meat.

The relationships between farmers' behavior toward veal calves, calves' responses to handling and transport, and veal meat quality were assessed. Two groups of 10 veal units were selected based on previous observed farmers' behavior toward the calves: one group consisted of farmers who had shown predominantly "positive" behavior toward the calves, and the other group of farmers had shown predominantly "negative" behavior. Calves were observed for their reactions to people at the unit, and 20 calves per veal unit were transported either directly to the slaughterhouse or subjected to additional transport consisting of a supplementary 20-min transport with additional unloading and loading. The effort needed to load the calves onto the truck and their behavior during loading was observed. During loading and unloading, and during lairage at the slaughterhouse, potentially traumatic incidents (falling down, hits against structures, slips) were recorded, and heart rate and cortisol measurements were taken. Carcasses were evaluated on their weight, color, conformation, pH, and bruise level. A meat sample was taken from the longissimus thoracis muscle for physical, chemical, and sensory analysis. Calves originating from "positive behavior" units showed fewer fear responses to people at the veal unit, needed less effort to be loaded to the truck, had lower heart rates during loading and unloading, and had fewer incidents at the slaughterhouse than calves from "negative behavior" units (P < 0.05). Carcasses from calves from "positive behavior" units were paler, and analyses of the meat sample revealed lower pH, moisture level, and redness compared to carcasses from calves from "negative behavior" units (P < 0.05). Additional transport led to a lower cortisol level after transport and to higher carcass pH values at slaughter compared to direct transport (P < 0.05) but did not affect meat quality. We concluded that farmers' positive behavior toward veal calves during rearing is likely to reduce the emotional responses of calves to handling and transport and to lead to fewer incidents, compared to negative behavior. This reduction of calves' emotional responses seems to be the reason for improved veal meat color.

Animals↗

[Surgical repair of degenerative atrial valve: long-term results].

BACKGROUND: The advantages of mitral valve repair in myxomatous regurgitation are well established. The durability of this reconstructive procedure is variable. The timing of operation is the surgeon dilemma. The aim of this study was to evaluate the early and long-term results of mitral valve repair in myxomatous regurgitation. METHODS: Between January 1990 and December 1997, 121 patients (77 males, 44 females) were operated on for myxomatous regurgitation with mitral valve repair. The surgical indication was based on the severity of mitral valve insufficiency and left ventricular dysfunction rather than the functional class. The surgical techniques were: quadrangular resection of the posterior mitral leaflet and sliding suture, triangular resection of the anterior mitral leaflet, chordal transposition and neo-chords suture, prosthetic ring (Carpentier-Edwards and Biflex rings) suture. RESULTS: There was 1 hospital death (0.8%). Long-term follow-up between 6 months and 107 months was available in 100% surviving patients. There were 6 late deaths, 3 for cardiac and 3 for non-cardiac events. CONCLUSIONS: Valve repair in mitral regurgitation caused by myxomatous disease provides excellent survival results at 51 months. Adverse outcome occurs in patients with preoperative left ventricular dysfunction, even if asymptomatic.

Adult↗