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Biomedical subjects

A Giusti

Publications and source records attributed to A Giusti.

At least 19 recordsLinked to original sources

High prevalence of secondary hyperparathyroidism due to hypovitaminosis D in hospitalized elderly with and without hip fracture.

OBJECTIVES: To determine and compare the prevalence of secondary hyperparathyroidism (HPTH) in a population of community-dwelling and institutionalized older adults hospitalized with and without hip fracture, and to evaluate factors correlated with secondary HPTH in this population. METHODS: Circulating concentrations of serum intact PTH, 25-hydroxyvitamin D [25(OH)D] total serum calcium and albumin were measured in 160 subjects with an osteoporotic fracture of the proximal femur and in 160 matched controls hospitalized for a disease unrelated to bone status. Patients with secondary causes of bone loss and taking medications affecting bone metabolism were excluded. Age, sex, place of residence and the ability to perform basic activities of daily living (BADL) two weeks before hospital admission were recorded at baseline. RESULTS: Patients were comparable with regard to the baseline demographic, biochemical and functional characteristics. The overall prevalence of secondary hyperparathyroidism was 51.2%, without significant differences between hip fractured patients and controls (50.6 vs 51.9%, p=0.911). In bivariate analysis only the age and functional status (BADL) demonstrated a significant relationship with secondary HPTH, while sex and place of residence were not significant. These results were also confirmed in multivariate analysis. Particularly, the risk of secondary HPTH increased with age and with the number of functions lost in BADL: patients fully dependent showed a 3 times as high risk (odd ratio 3.07, 95% confidence interval 1.73 to 5.46, p=0.000) compared to patients independent in BADL, and subject aged >88 yr had a twice as high risk of developing secondary HPTH compared to younger ones (odd ratio 2.28, 95% confidence interval 1.20 to 4.32, p=0.012). CONCLUSION: These results show that secondary HPTH due to hypovitaminosis D is a frequent disorder in hospitalized elderly, strongly correlated with the functional status, irrespective of sex and place of residence.

Aged↗

Generalised wavelet analysis of cutaneous flowmotion during post-occlusive reactive hyperaemia in patients with peripheral arterial obstructive disease.

The purpose of the present study was to assess whether the generalised wavelet analysis (GWA) of the leg cutaneous laser Doppler (LD) flowmotion waves recorded during baseline (Bsl) and after skin post-occlusive hyperaemia (POH) can provide information on the leg cutaneous microcirculatory adaptation to stage II peripheral arterial obstructive disease (PAOD). With this aim the flowmotion was characterised in 20 healthy subjects (HS) and 20 stage II PAOD patients by GWA of LDF tracings during Bsl and POH test. The vascular endothelial and smooth muscle function was also evaluated exploring the arm skin vasodilatory response to iontophoretically delivered acetylcholine (Ach) and sodium nitroprusside (SNP) using LD. During Bsl there was no significant difference in leg skin perfusion between HS and PAOD patients (7.3+/-5.6 vs. 5.8+/-2.9 AU, respectively). PAOD patients revealed higher peak powers in the frequency interval of 0.007-0.02 Hz (120+/-82 vs. 85+/-62 AU(2)/Hz; P < 0.05), 0.02-0.06 Hz (116+/-128 vs. 63+/-48 AU(2)/Hz, respectively; P < 0.05) and 0.06-0.2 Hz (39+/-49 vs. 14+/-10 AU(2)/Hz; P < 0.05). These flowmotion frequencies are related to vascular endothelium activity, sympathetic activity and vessel wall myogenic activity, respectively. During POH the mean peak power of the flowmotion waves increased significantly (P < 0.05) in HS respect to Bsl with the only exception of the 0.02-0.06 Hz band. In the PAOD patients, compared to Bsl the amplitude of the flowmotion waves did not significantly change during POH. In addition, the PAOD patients presented an increased time from release to peak-flux (18.25+/-15.5 vs. 2.16+/-1.28 s, respectively; P < 0.05), an increased time from release to recovery of the basal perfusion (90.26+/-39.14 vs. 26.55+/-14.05 s, respectively; P < 0.05) and a lower slope of the POH curve (10+/-15 vs. 54+/-17 degrees , respectively; P < 0.05), compared with HS. The cutaneous arm vasodilatory response to Ach and to SNP was reduced in PAOD patients in comparison with HS (P < 0.001). In conclusion, our findings showed an increased amplitude of the frequency interval 0.007-0.02, 0.02-0.06 and 0.06-0.2 Hz during Bsl in PAOD patients which did not change during the POH test. All data suggest that in stage II PAOD patients the leg skin perfusion is not impaired during Bsl because of a compensatory mechanism related to increased endothelial, myogenic and sympathetic activities. However during reactive hyperaemia these mechanisms appear to be exhausted in accordance with the reduced vasoreactivity to Ach and SNP.

Acetylcholine↗

Effects of diagnostic cardiac ultrasound on oxygen free radical production and microvascular perfusion during ischemia reperfusion.

Diagnostic ultrasound (US) is reported to increase intracellular oxidative stress in vitro. Increased oxidative stress mediated ischemia-reperfusion injury in the microcirculation. To examine the effects of US in hamster cheek pouch microcirculation during baseline and ischemia and reperfusion (I/R), I/R injury was provoked in the cheek pouch under "sham" (transducer off, group 1) and active US irradiation (group 2) at baseline (15 min) and at the beginning (15 min) of the reperfusion after ischemia (30 min). US transmission was delivered in the harmonic mode (2.5 MHz) with 1.3 mechanical index (MI) and 2.0 peak negative pressure. Microvascular damage was evaluated by measuring arterial diameter, red blood cell velocity, wall shear stress, permeability, perfused capillary length and adherent leukocytes in venules. Lipid peroxides were determined in the systemic blood. US increased permeability (baseline: 0.04 +/- 0.02; after US 0.30 +/- 0.04, p < 0.01) and slightly decreased capillary perfusion by 7% during baseline (p < 0.01). Arteriolar diameter (35 +/- 7 microm vs. 20 +/- 5 microm, p < 0.05), RBC velocity (2.8 +/- 0.4 mm s(-1) vs. 0.75 +/- 0.05 mm s(-1), p < 0.05) and shear stress ( 0.76 +/- 0.09 Pa vs. 0.36 +/- 0.05 Pa, p < 0.05) decreased significantly after reperfusion. These parameters increased by 40, 64 and 33%, respectively after US. Leukocyte adhesion decreased by 31 % (p < 0.05) after US and lipid peroxides decreased by 26% and 51% during baseline and 15 min of reperfusion after US, respectively. In conclusion, diagnostic US increased microvascular permeability during baseline and reperfusion. Moreover, US enhanced wall shear stress and reduced oxidative stress during postischemic reperfusion; thus, increasing capillary perfusion.

Animals↗

A randomised controlled trial on the efficacy of hydroelectrophoresis in acute recurrences in chronic low back pain patients.

AIM: Physical therapy efficacy in the treatment of low back pain (LBP) has been widely debated and is far from achieving high levels of evidence. Hydroelectrophoresis (Hydrofor) is a novel method of driving drugs through the dermal tissue, which has been proposed for muscle pain treatment. Aim of this randomised placebo-controlled study was to ascertain the efficacy of Hydrofor treatment on acute relapsing episodes of pain in chronic LBP subjects. METHODS: Eighteen under-50 adults (M/F: 7/11; age 35+/-8 years) suffering from chronic LBP were enrolled within 3 to 4 days of back pain relapse. After a complete clinical and functional assessment patients were randomly divided into 2 equal groups. Group A received 3 Hydrofor applications of a mixture containing both NSAIDs and muscle relaxants, whereas Group B received 3 Hydrofor applications of a drug-free solution. Afterwards, both groups performed the same rehabilitation treatment consisting of 7 group sessions of standard physiotherapy, including stretching, range of motion and extension exercises. The Oswestry disability index (ODI), the Million instrument scale and a visual analogue scale (VAS) were chosen as outcome measures and applied at baseline, after Hydrofor/placebo applications, after completion of rehabilitation sessions and, at last, 2 months later. The two-way Friedman test was used to analyse within-group (time effect) and between-group (time x group effect) differences. RESULTS: All subjects declared a significant pain reduction since the first Hydrofor application. Pain evolution overlapped in the 2 groups until the 3rd session, after which Group A significantly diverged from Group B, as they affirmed a greater symptom reduction than controls (time x group effect: VAS: F = 7.4, p <0.01). Such difference disappeared after the physiotherapy sessions as well as 2 months later (time x group effect: VAS: F = 2.1, p =0.08). Pain-related disability showed a greater reduction in Group A than B immediately after Hydrofor application (time x group effect: ODI: F=3.9 p <0.05; Million: F=4.1 p<0.05), but the mean scores almost overlapped at the 2 month follow-up (time x group effect: ODI: F=2.3 p =0.08; Million: F=1.3 p=0.26). CONCLUSIONS: Hydrofor treatment relieves relapsing LBP and could be recommended to active adults as a safe technique shortening the time needed to achieve functional restoration.

Journal Article↗

Microvascular oxygenation, oxidative stress, NO suppression and superoxide dismutase during postischemic reperfusion.

Increased formation of reactive oxygen species (ROS) on reperfusion after ischemia underlies ischemia-reperfusion (I/R) damage. We measured, in real time, oxygen tension in both microvessels and tissue and oxidant stress during postischemic reperfusion in the hamster cheek pouch microcirculation. We measured Po2 by using phosphorescence quenching microscopy and ROS production in the systemic blood. We evaluated the effects of a nitric oxide synthase inhibitor (NG-monomethyl-L-arginine, L-NMMA) and SOD on the oxidative stress during reperfusion. Microvascular injury was assessed by measuring diameter change, the perfused capillary length (PCL), and leukocyte adhesion. During early reperfusion, arteriolar Po2 was significantly lower than baseline, whereas capillary Po2 varied between 7 and 0 mmHg. Arterial blood flow did not regain baseline values, whereas Po2 returned to baseline in arterioles and tissue after 30 min of reperfusion. During 5 and 15 min of reperfusion, ROS increased by 72 and 89% versus baseline, respectively, and declined to baseline after 30 min of reperfusion. Pretreatment with SOD maintained ROS at normal levels, increased arteriolar diameter, blood flow, and PCL, and decreased leukocyte adhesion (P < 0.05). L-NMMA decreased ROS only within 5 min of reperfusion, which increased significantly by 72% later during reperfusion. L-NMMA worsened leukocyte adhesion (P < 0.05). In conclusion, our results show that the early reperfusion is characterized by low Po2 linked to increased production of ROS. At early reperfusion both SOD and L-NMMA decreased ROS production, whereas only SOD reduced it during later reperfusion. We suggest that low-flow hypoxia profoundly affects vascular endothelial damage during reperfusion through changes in ROS and nitric oxide production.

Animals↗

Glucose-insulin-potassium treatment in combination with dipyridamole inhibits ischaemia-reperfusion-induced damage.

AIMS/HYPOTHESIS: Treatment with intravenous glucose-insulin-potassium has beneficial effects in reperfused patients, reducing mortality in patients with myocardial infarction by 28 %. We hypothesized that insulin response to glucose-insulin-potassium infusion might lead to vasodilation in ischemia/reperfusion (I/R). Hyperglycaemia and hyperinsulinaemia determine oxidative stress. We therefore investigated the microcirculatory changes following I/R after glucose-insulin-potassium or in association with glucose-insulin-potassium dipyridamole in hamster cheek pouch. METHODS: The control (I/R), glucose-insulin-potassium groups with and without dipyridamole were treated with saline, 300 g/l, 50 U/l insulin and 80 meq/l KCl infused at 0.2 ml. 100 g-1. h-1, and GIK plus dipyridamole (0.084 mg. 100 g-1 intravenously) at beginning, 30 min before ischaemia, and continuing through reperfusion. We measured microvessel diameter changes, arteriolar red blood cell velocity, permeability increase, capillary perfused length, leukocyte and platelet adhesion. RESULTS: Hyperglycaemia and hyperinsulinaemia did not cause vasodilation whereas in the glucose-insulin-potassium group with dipyridamole there was a marked arterial vasodilation with increased red blood cell velocity and perfused capillary length at reperfusion. Glucose-insulin-potassium infusion reversed the arterial vasoconstriction caused by I/R at reperfusion. Adhering leukocytes to venules decreased by 56 and 86 % while platelets adhering to microvessels was reduced by 52 and 72 % at reperfusion in glucose-insulin-potassium groups with and without dipyridamole, respectively. The permeability was decreased by GIK and completely suppressed by GIKD after I/R. Conclusion hypothesis: We demonstrated that GIK, when used in combination with dipyridamole, had beneficial effects on the capillary perfusion against I/R-induced injury. There was a marked reduction of leukocyte and platelet adhesion that can be explained by the antioxidant properties of dipyridamole.

Animals↗

Molecular characterization of chromosome 22 deletions by short tandem repeat polymorphism (STRP) in patients with conotruncal heart defects.

The haploinsufficiency of chromosome 22q11.2 can cause both DiGeorge and velocardiofacial syndromes, both of which are characterized by conotruncal heart defects as well as a wide range of other extracardiac anomalies. Several studies have demonstrated that approximately 10-20% of patients with conotruncal heart defects have a 22q11.2 deletion. In clinical laboratories, the deletion is usually detected by fluorescent in situ hybridization (FISH). We set up a polymerase chain reaction-based non-radioactive method for molecular analysis of the 22q11.2 region in conotruncal cardiac patients with conotruncal defects. Sixty-four children with conotruncal defects and their parents were genotyped by polymerase chain reaction, using fifteen polymorphic markers. We identified nine deletions (confirmed by FISH): eight were "de novo" and one familial, maternally inherited. Six deletions were of paternal and three of maternal origin. There were seven deletions of 3 Mb and the other two were of 1.5 Mb. This method is a cost-effective means of characterizing the 22q11.2 region and it can be applied for a rapid screening of 22q11.2 deletion in patients at risk. In agreement with previously published data, we found no correlation between the sizes and the parental origin of deletions and cardiac or extra-cardiac phenotypes.

Adolescent↗

Pharmacokinetics and pharmacodynamics of zofenopril in healthy volunteers.

This study was carried out to investigate the pharmacokinetics of zofenopril (CAS 81938-43-4) and zofenoprilat, the behaviour of the angiotensin converting enzyme (ACE) (pharmacodynamics) following the administration of zofenopril calcium at the single oral dose of 60 mg in eighteen healthy volunteers. This open label, one-way study was carried out in a single centre on 18 healthy volunteers. The volunteers received an oral single 60 mg dose of zofenopril calcium following an overnight fast. The tablet was swallowed with 250 ml of water. Fasting continued for additional 4 h after dosing and no other liquid intake was allowed from 1 h before to 2 h after administration. Plasma concentrations of zofenopril and its active metabolite zofenoprilat as well as serum ACE activity were measured before drug intake (baseline) and on timed samples over a 36 h period after dosing by LC-MS-MS, a highly sensitive, validated method for active moiety concentrations. Peak plasma concentration was reached on average at 1.19 h with zofenopril and at 1.36 h with zofenoprilat. Concentrations then decreased reaching values under or close to the limit of quantitation (1 ng.ml-1 for zofenopril, 2 ng.ml-1 for zofenoprilat) from 8 to 16 h after dosing. Complete inhibition of ACE was seen at the first blood sampling time (1 h) and lasted on average up to 9.44 h. ACE activity then slowly reactivated, but enzyme inhibition continued and was estimated to be 74% and 56% at 24 and 36 h following drug administration, respectively. From these data a complete or almost complete enzyme inhibition is expected with zofenopril given in repeated dose regimen.

Adult↗

Stimulation of the apoptotic response as a basis for the therapeutic synergism of lonidamine and cisplatin in combination in human tumour xenografts.

The pharmacological interest in lonidamine is related to its ability to enhance the cytotoxic effects of several DNA-damaging anti-tumour agents. This study was undertaken to better understand the in vivo interaction between lonidamine and cisplatin in the treatment of human tumour xenografts, including three carcinoma models characterized by a different responsiveness to cisplatin, in spite of the presence of a wild-type p53 gene in all tumours. The drug combination was more effective in tumour growth inhibition than cisplatin alone against MX-1 breast carcinoma and A2780 ovarian carcinoma, both highly responsive to cisplatin, whereas no influence of ionidamine was observed on anti-tumour activity of cisplatin in the treatment of the relatively resistant IGROV-1 ovarian carcinoma. As cisplatin activity is related to induction of apoptosis, the modulation of drug-induced apoptosis by lonidamine was investigated. Under conditions in which lonidamine itself had negligible effects on tumour growth and apoptosis, the modulating agent stimulated the apoptotic response induced by cisplatin in the responsive but not in the resistant tumours. Tumour response was dependent not only on the drug activation of apoptosis, but mainly on the persistence over time of the event. In the breast carcinoma MX-1, hypersensitive to cisplatin and to the lonidamine+cisplatin combination, the efficacy of drug treatment was associated with phosphorylation of bcl-2 followed by down-regulation of the protein. Lonidamine itself caused a delayed phosphorylation of bcl-2. These results are consistent with the interpretation that lonidamine is effective in modulating biochemical factors involved in regulation of apoptosis.

Animals↗

Tobacco smoking and risk of haematological malignancies in adults: a case-control study.

A retrospective study was conducted in 1216 cases to investigate the possible association between tobacco smoking and the risk of haematological malignancies. A small, but not significant, increase in malignancy was observed in smokers. Significant association was demonstrated between tobacco smoking and acute nonlymphoblastic leukaemia, and myelodysplastic syndromes. The duration and amount smoked increased the risk; heavy smokers presented significant positive associations with overall malignancies, acute nonlymphoblastic leukaemia, myelodysplastic syndromes, and monoclonal gammopathy of undetermined significance, whereas light smokers did not present any significant association. These data support a causal relationship between certain haematological malignancies and tobacco smoking. Further research is needed to examine the risk according to dose-response effect, and the variation in risk according to the histological subtype of the malignancy.

Adolescent↗

A hox/hom homeobox gene in sponges.

The hox/hom homeobox genes code for DNA-binding proteins that confer positional information during animal development; these genes have been found in a wide range of triploblasts and in cnidarians. We report here the identification of a hox/hom gene and two other homeobox genes in the genomes of sponges. This finding extends the detection of hox/hom genes to the lowest metazoan phylum and suggests a monophyletic origin of the kingdom Animalia. Because, in culture, sponge cells quickly reaggregate, differentiate and construct tissue after disaggregation, they can provide a useful model system for characterization of the basic roles of homeobox genes in the control of cellular differentiation.

Amino Acid Sequence↗

A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis.

In order to assess the liver protective activity and the antioxidant properties of a new silybin complex (IdB1016), we carried out a short-term pilot study on 20 patients with chronic active hepatitis (CAH), randomly assigned to 240 mg of silybin b.i.d. (10 patients, 4 m/6 f, mean age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood samples were collected before and after 7 days of treatment for liver function tests (LFTs), malonaldehyde (MDA) as an index of lipid peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in protecting cells against free radical-mediated lipid peroxidation. In the treated group, there was a statistically significant reduction of mean (+/- SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0 (+/- 13.3) to 65.9 (+/- 7.5) u/l, (p < 0.01), of alanine aminotransferase (ALT) from 115.9 (+/- 12.9) to 82.5 (+/- 10.6) u/l (p < 0.01), of gamma-glutamyltranspeptidase (gamma-GT) from 51.4 (+/- 9.3) to 41.3 (+/- 4.2) u/l (p < 0.02) and of total bilirubin (TB) from 0.76 (+/- 0.08) to 0.53 (+/- 0.04) mg/dl (p < 0.05). Alkaline phosphatase (AP) fell slightly from 143.4 (+/- 6.4) to 137.5 (+/- 7.8) u/l. There were no significant changes in MDA, Cu or Zn serum concentrations. These results show that IdB1016 may improve LFTs related to hepatocellular necrosis and/or increases membrane permeability in patients affected by CAH.

Adult↗

[Ursodeoxycholic hemisuccinate in the treatment of chronic active hepatitis. A controlled clinico-therapeutic study].

This controlled study was performed on 36 patients affected by HBV and/or HCV correlated chronic hepatitis (CAH). Eighteen of them received 300 mg of UDCA-hemisuccinate orally twice a day for six months; the other 18 received 200 mg of S-adenosyl-methionine (SAMe) twice a day for six months. The two groups were determined randomly. Treatment with UDCA-hemi-succinate produced a statistically significant reduction in ALT (from 167 +/- 17 to 119 +/- 15 U/l; p < 0.0001), AST (from 122 +/- 14 to 86 +/- 11 U/l; p < 0.0001) and y-GT (from 81 +/- 10 to 53 +/- 6 U/l, p < 0.0001). The results obtained suggest that UDCA-hemi-succinate may be useful in the long-term treatment of chronic liver diseases of viral aetiology because it improves the biochemical parameters of hepatocellular necrosis and/or increased liver cell permeability.

Adult↗

[Neonatal infections and premature rupture of fetal membranes].

The premature rupture of the membranes is still a cause of concern due to the related risk of infection and respiratory disorders. The study included sixty-two neonates whose mothers had ruptured their membranes for at least 48 hours (group A) and 42 neonates with a high risk of infection (low birth weight, prematurity) (group B) in order to assess whether antibiotic prophylaxis used in pregnant women with premature rupture of the membranes is sufficient to reduce the risk of severe neonatal infection. The results obtained show that there is an increased frequency of RDS, jaundice and mortality in group A, whereas in group B there was a greater frequency of sepsis and urinary tract infections. Antibiotic prophylaxis therefore allows the frequency of neonatal infections following the rupture of membranes to be reduced, thus enabling the birth to be delayed in order to induce pulmonary maturity.

Anti-Bacterial Agents↗

[Glycerol erythrocyte lysis test in the 1st month of life in neonates at term and premature infants].

Foetal erythrocytes have an enhanced resistance to osmotic haemolysis that they retain for the first 5 days after birth, particularly in premature newborns. The erythrocyte fragility test was used to study the increased resistance to osmotic haemolysis in 155 healthy newborns (50 NGA born to term, 55 NGA premature and 50 SGA born to term) as well as 31 newborns (20 born to term and 11 premature) with aspecific hyperbilirubinaemia. The drug used was glycerol which is specific in its reaction to alterations in erythrocyte membrane stability and made it possible to assess changes arising in the first month after birth, both naturally and in response to phototherapy. The results show a much higher resistance in neonatal than adult erythrocytes that gradually decrease during the first month after birth without, however, falling to adult levels. No changes in resistance attributable to the phototherapy adopted in newborns with hyperbilirubinaemia were encountered. The glycerol test proved extremely sensitive in the diagnosis of neonatal haemolytic anaemias easy to use so that congenital spherocytosis can be identified earlier than is otherwise possible.

Anemia, Neonatal↗

[Proposed scoring system for the early diagnosis of infection in neonates].

Infections are currently often responsible for neonatal morbidity and mortality. The present study examines the possibility of reducing this incidence by the early diagnosis of infections. With this in mind the early clinical signs of infection were examined as well as the results of certain quickly and easily performed blood and blood chemical tests which were scored from 0 to 2. The results showed that newborns with scores less than 5 should be considered free of sepsis, those scoring 5-7 should arouse suspicion of sepsis, while sepsis should be considered definitely present in those scoring greater than 7. This scoring system presented 100% sensitivity, 88.2% specificity as well as 100% positive and an 88.2% negative predictive value. The system is therefore considered reliable as well as easy to use.

Humans↗