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Biomedical subjects

G Brunetti

Publications and source records attributed to G Brunetti.

At least 19 recordsLinked to original sources
PubMed2005

L-carnitine and isovaleryl L-carnitine fumarate positively affect human osteoblast proliferation and differentiation in vitro.

Age-related bone loss is characterized by decreased osteoblast activity, possibly related to the reduction of energy production. Carnitine promotes energy availability and its concentration declines with age; Therefore, two Carnitine derivatives, L-carnitine fumarate (LC) and isovaleryl L-carnitine fumarate (Iso-V-LC), have been tested on several parameters of human osteoblasts in vitro. Both compounds significantly increased osteoblast activity, but the new compound Iso-V-LC was more efficient than LC at lower concentrations. They both significantly enhanced cell proliferation, [3H]-proline incorporation and the expression of collagen type I (COLLI), and the bone sialoproteins (BSPs) and osteopontin (OPN). The percentage of alkaline phosphatase (ALP)-positive cells and the secretion of osteocalcin were not modified by LC and Iso-V-LC. Both molecules increased the formation of mineralized nodules, but Iso-V-LC reached the maximum effect at a concentration 10-fold lower than that of LC. Furthermore, we showed that insulin-like growth factor (IGF)-I and IGF-II mRNA levels were not modified by the treatment. However, the two compounds induced an increase of insulin-like growth factor binding protein (IGFBP)-3 and a decrease of IGFBP-5 in both osteoblast lysates and the extracellular matrix (ECM). In conclusion these data suggest that carnitine and, in particular, its new derivative, Iso-V-LC supplementation in the elderly may stimulate osteoblast activity and decrease age-related bone loss.

Alkaline Phosphatase↗
PubMed2005

Bioequivalence of a new liquid formulation of ursodeoxycholic acid (Ursofalk suspension) and Ursofalk capsules measured by plasma pharmacokinetics and biliary enrichment.

BACKGROUND: Ursodeoxycholic acid is an approved therapy for hepatobiliary disorders but in infants and children compliance is compromised because it is formulated exclusively as capsules, or tablets. AIM: To determine the pharmacokinetics and bioequivalence of a new liquid formulation of ursodeoxycholic acid (Ursofalk suspension) with a standard capsule (Ursofalk) in a randomized, unblinded, crossover designed study of 24 healthy adults. METHODS: Equivalence was based on single bolus oral plasma pharmacokinetics and biliary ursodeoxycholic acid enrichments after repeat doses. Biliary bile acid composition and hydrophobicity index were also compared. Ursodeoxycholic acid was measured in duodenal bile by high-performance liquid chromatography and in plasma by mass spectrometry. RESULTS: The mean percentage biliary ursodeoxycholic acid enrichment after administration of the suspension was not significantly different from that obtained with capsules (44.2 +/- 11.7% vs. 46.9 +/- 10.2%, respectively). The equivalence ratio was 0.94 (95% CI: 0.8-1.1), establishing bioequivalence between suspension and capsules. Both formulations reduced the biliary hydrophobicity index and no differences in bile acid composition were observed between formulations. The plasma pharmacokinetics of both formulations was similar and the tolerability of the suspension was excellent. CONCLUSIONS: A new liquid formulation of ursodeoxycholic acid suitable for paediatric patients is pharmacologically bioequivalent to capsules when given as single, or repeated oral doses.

Adolescent↗
PubMed2005

T cells support osteoclastogenesis in an in vitro model derived from human periodontitis patients.

BACKGROUND: Periodontitis is characterized by alveolar bone destruction; however, the mechanisms responsible for bone damage are poorly understood. It has been reported that T cells are implicated in the pathogenesis of periodontitis. It has been also demonstrated that activated T lymphocytes secrete receptor activator of nuclear factor-kappa B ligand (RANKL) and can support the differentiation of monocytes into resorbing osteoclasts (OCs). Therefore, the purpose of this study was to examine the OC formation in periodontitis patients (PP) and the role of T cells in osteoclastogenesis. METHODS: To study OC formation, we used an in vitro model consisting of unstimulated and unfractionated peripheral blood mononuclear cells (PBMCs) from PP and controls. In parallel, T-cell-depleted PBMCs from the same patients were also established. The expression of RANKL and tumor necrosis factor-alpha (TNF-alpha) was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot in fresh T cells isolated from PP and controls. Functional antibodies, anti-RANKL and anti-TNF-alpha, were utilized to study osteoclastogenesis in PBMC cultures from PP. RESULTS: We showed that, in unfractionated PBMCs from PP, the OCs spontaneously developed in a T-cell-dependent way. The addition of macrophage colony stimulating factor (MCSF) and RANKL was necessary to promote the osteoclastogenesis in T-cell-depleted PBMC cultures from PP and in unfractionated PBMCs from periodontally healthy controls. Moreover, freshly isolated T cells from PBMCs of PP overexpressed RANKL and TNF-alpha. Finally, functional anti-RANKL and anti-TNF-alpha antibodies significantly inhibited osteoclastogenesis. CONCLUSION: Our data suggest that T cells support spontaneous osteoclastogenesis in PP via RANKL and TNF-alpha overexpression.

Adult↗
PubMed2002

Sudden improvement of respiratory failure in a woman with carcinoma of the colon.

We present a case of bronchial and endotracheal metastases completely blocking the left main bronchus and partially occluding the middle lobe bronchus contributing to severe respiratory failure. The patient's lack of consent to laser resection of the mass led to the use of chemotherapy; after the first cycle of treatment a neoplastic mass about 3 cm long was spontaneously expelled with a cough. The expulsion of the metastasis caused rapid improvement of the dyspnea and gas exchange; however, the continuation of the chemotherapy did not bring any further benefit to the patient, who died 115 days after diagnosis.

Adenocarcinoma, Mucinous↗
PubMed2001

GABA(B) receptor inhibition causes locomotor stimulation in mice.

The present study investigated the effect of the administration of the GABA(B) receptor antagonists, SCH 50911 [(2S)(+)-5,5-dimethyl-2-morpholineacetic acid], CGP 46381 [(3-aminopropyl)(cyclohexylmethyl)phosphinic acid] and CGP 52432 (3-[[(3,4-dichlorophenyl)methyl]amino]propyl]diethoxymethyl)phosphinic acid), on spontaneous locomotor activity in mice. All drugs were acutely administered at the doses of 10 and 30 mg/kg (i.p.). The dose of 30 mg/kg of all drugs resulted in a significant stimulation of locomotor activity. The locomotor stimulation elicited by SCH 50911 was completely blocked by haloperidol (0.1 mg/kg, i.p.), suggesting that hyperactivity induced by blockade of the GABA(B) receptor is mediated by enhanced dopamine release. These results suggest the existence of a GABA(B) receptor-mediated tonic inhibition of dopamine neurons.

Animals↗
PubMed2001

The cannabinoid receptor antagonist SR 141716 prevents acquisition of drinking behavior in alcohol-preferring rats.

The cannabinoid CB(1) receptor antagonist, N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide) (SR 141716); 0.3-3 mg/kg, i.p., twice daily for 10 days), prevented the acquisition of alcohol drinking behavior in rats genetically selected for alcohol preference (Sardinian alcohol-preferring (sP) rats), having the free choice between alcohol (10%, v/v) and water. The results suggest that activation of cannabinoid CB(1) receptors is essential for the acquisition of alcohol drinking behavior in animals with a genetically determined alcohol preference.

Alcohol Drinking↗
PubMed2001

Role of GABA(B) receptors in the sedative/hypnotic effect of gamma-hydroxybutyric acid.

The present study was aimed at identifying the receptor systems involved in the mediation of the sedative/hypnotic effect of gamma-hydroxybutyric acid (GHB) in DBA mice. Administration of the putative antagonist of the GHB binding site, 6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS-382; 50-500 mg/kg, i.p.), significantly increased the duration of loss of righting reflex induced by GHB (1000 mg/kg, i.p.). In contrast, the GABA(B) receptor antagonists, (2S)(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911; 25-100 mg/kg, i.p.) and (3-aminopropyl)(cyclohexylmethyl)phosphinic acid (CGP 46381; 12.5-150 mg/kg, i.p.), completely prevented the sedative/hypnotic effect of GHB. SCH 50911 (100 and 300 mg/kg, i.p.) was also capable to readily reverse the sedative/hypnotic effect of GHB (1000 mg/kg, i.p.) in mice that had lost the righting reflex. SCH 50911 (100 mg/kg, i.p.) also completely abolished the sedative/hypnotic effect of the GABA(B) receptor agonist, baclofen. These results indicate that the sedative/hypnotic effect of GHB is mediated by the stimulation of GABA(B) receptors and add further support to the hypothesis that the GABA(B) receptor constitutes a central site of action of GHB.

Animals↗
PubMed2001

Selective breeding of two rat lines differing in sensitivity to GHB and baclofen.

Two Wistar-derived rat lines, one sensitive (GHB-S) and the other resistant (GHB-R) to the anesthetic effect of gamma-hydroxybutyric acid (GHB), have been selectively bred. GHB-S and GHB-R rats were also sensitive and resistant, respectively, to the anesthetic effect of baclofen, the prototype GABA(B) receptor agonist, suggesting that they may be useful to elucidate not only the role of endogenous GHB but also that of GABA(B) receptors in sleep and anesthesia.

Anesthesia Recovery Period↗
PubMed2001

Procedure of bidirectional selective outbreeding for production of two rat lines differing in sensitivity to the sedative/hypnotic effect of gamma-hydroxybutyric acid.

The exogenous administration of gamma-hydroxybutyric acid (GHB), a constituent of the mammalian brain where it likely functions as a neurotransmitter or a neuromodulator, exerts a number of pharmacological effects, including sedation and hypnosis. The present paper describes a procedure for selective breeding of two rat lines which markedly differ in sensitivity to the sedative/hypnotic effect of GHB. Selective breeding originated from Wistar rats showing opposite sensitivity to the sedative/hypnotic effect of 1 g/kg GHB (i.p.). 'Sensitive' Wistar rats, defined as those individuals displaying values of r = sleep time/onset greater than the upper 15th percentile, were mated to generate the GHB-sensitive (GHB-S) line; conversely, 'resistant' Wistar rats (r-values lower than the lower 15th percentile) were mated to generate the GHB-resistant (GHB-R) line. Upper and lower 15th percentiles were also used to establish the selection cut-offs and criteria for rats of subsequent generations. Specifically, r-values of GHB-S rats were required to be r > or =8 on two separate tests with GHB; r-values of GHB-R rats were required to be r < or =2 on two separate tests with GHB. In each of the three generations produced to date, GHB-S rats showed significantly shorter onset, longer sleep times and greater r-scores than GHB-R rats. The selective breeding of GHB-S and GHB-R rats: (a) suggests that sensitivity to GHB is under genetic control, and (b) may constitute a unique model for investigation of the physiological function of GHB.

Animal Husbandry↗
PubMed2001

Ursodeoxycholic acid complexation with 2-hydroxypropyl-beta-cyclodextrin increases ursodeoxycholic acid biliary excretion after single oral administration in rats.

Complexation of ursodeoxycholic acid (UDCA) with 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) improves the water solubility and the dissolution rate of UDCA and may therefore increase its bioavailability. We compared the amount and the rate of biliary excretion of UDCA and biliary lipid secretion after a single oral administration of UDCA in 3 different pharmaceutical formulations [UDCA-HPbetaCD ('urso-beta-cyclodextrin'), UDCA suspension and UDCA capsule] at 3 different dosages each, in 11 groups (2 control groups) of bile fistula rats. UDCA excretion increased with an increase in dose, biliary UDCA recovery and peak secretion were significantly higher after administration of UDCA-HPbetaCD than after UDCA in suspension or capsule. This enhancement of biliary excretion may achieve greater UDCA enrichment in the bile acid pool than conventional pharmaceutical UDCA formulations, this giving to UDCA-HPbetaCD a considerable therapeutical potential.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2001

Non-invasive pressure support ventilation in acute hypoxemic (non hypercapnic) respiratory failure. Observations in Respiratory Intermediate Intensive Care Unit.

BACKGROUND: Non-invasive positive pressure support ventilation (NIPSV). METHODS: In patients with acute hypoxaemic (PaO2/FiO2 &Mac178;100) non hypercapnic respiratory failure (ARF) admitted to a Respiratory Inter-mediate Intensive Care Unit of a general Hospital, between January 1993 and December 1997. RESULTS: In 21 selected patients (PaO2/ FiO2T0=82+/-9) NIPSV improved PaO2 in 13/21 patients (Group A) and did not improve in 8/21 patients (Group B) (PaO2/FiO2T1=154+/-25 in Group A vs PaO2/FiO2T1=106+/-7.5 in Group B, p=0.00001). Upon admission the two groups did neither significantly differ for blood gas values (PaO2/FiO2T0=84+/-9.6 in Group A vs 79.8+/-8.7 in Group B), nor for clinical status (APACHE II=19.8+/-5 in Group A vs 24.6+/-7 in Group B). Shorter duration of NIPSV in Group B patients (11.2+/-19.7 hrs vs 35.3+/-32.3 hrs in Group A, p=0.047), in spite of a rise in PEEP (9.3+/-2.3 in Group B vs 5.5+/-2.4 in Group A, p=0.003) and Pressure Support (18.7+/-1.8 in Group B vs 15+/-3.2 in Group A, p=0.004) was due to onset of conditions which required shifting from NIPSV to endotracheal intubation (ETI). OUTCOME: 8/21 patients were successfully treated by only NIPSV. 8/21 patients were intubated. 5/21 patients dead in RIICU; 1 month survival: 9/21 patients. Side effects: mask intolerance (3/21); skin necrosis (1/21); pneumothorax (1/21). CONCLUSIONS: NIPSV may be tried in ARF patients to improve PaO2 and avoid ETI.

AIDS-Related Opportunistic Infections↗
PubMed1999

Soluble interleukin 2 receptor (sIL2R) in monitoring advanced lung cancer during chemotherapy.

STUDY OBJECTIVES: To evaluate the usefulness of measuring sIL2R for diagnostic and prognostic purposes and for monitoring disease during a 6-month period of chemotherapy, and to investigate the clinical significance of sIL2R serum concentrations. METHODS: The serum concentration of sIL2R, TPA and lymphocyte subsets CD4, CD8, CD25, CD16 were measured at diagnosis and then 1 and 6 months after the start of chemotherapy. PATIENTS: There were 39 patients (three females, 36 males; mean age 61.6 years) with lung cancer (LC), treated with chemotherapy and 22 control subjects (six females, 16 males; mean age 50.1 years) with non-neoplastic lung diseases. RESULTS: No significant differences in sIL2R serum concentrations were observed at diagnosis between the control and LC group or when comparing the different histotypes, disease stages (IIIa-b vs IV) and survival (survival < or = 12 vs > 12 months). On comparing the sequential variations of the examined parameters a significant increase in sIL2R (P < 0.007) after 1 and 6 months versus basal value was observed only in patients surviving less than 12 months and in those who did not respond to chemotherapy. Moreover a negative correlation was observed between sIL2R serum concentrations and CD25+ and CD16+ lymphocyte subsets. Evaluation of survival curves of patients with basal sIL2R > or < or = 700 U/ml showed a slightly lower survival rate in the former group. CONCLUSIONS: The present results, confirming the poor utility of sIL2R in the diagnostic phase of the disease, show its usefulness in prognostic evaluation and in the clinical surveillance of patients with advanced lung cancer submitted to polychemotherapy. In this case any variations in sIL2R serum levels are likely to relate to the spread of the neoplasia rather than to the host immune response.

Adenocarcinoma↗
PubMed1998

Walking with the advanced reciprocating gait orthosis (ARGO) in thoracic paraplegic patients: energy expenditure and cardiorespiratory performance.

The aim of this study was to quantify the energy cost and the cardiorespiratory response while walking at free speed with an Advanced Reciprocating Gait Orthosis (ARGO). The study was conducted on a group of six male paraplegic patients, age range 16-31 years (median = 22.50), with complete traumatic injuries ranging from T3 to T12 and a median time lapse from the trauma of 21 months. The data was recorded 6-8 weeks after the patients were fitted and trained to use the orthosis. Maintaining a standing position produced a significant increase of both the heart rate (HR) and the respiratory rate (RR), whilst the increase of energy consumption was not significant. The data for median speed, energy consumption and energy cost observed during free walking was similar to that of the Reciprocating Gait Orthosis (RGO) in thoracic level paraplegic individuals. This study indicates that in the utilisation of the ARGO the workload is not excessive when it is limited to maintaining a standing position. In contrast, walking results in early anaerobic conditions and unsustainable fatigue after short distances. The great energy cost recorded is considered to be a main reason for the frequent abandonment or the low utilisation of the orthosis at follow-up.

Adolescent↗
PubMed1996

Prevention with sucralfate gel of NSAID-induced gastroduodenal damage in arthritic patients.

OBJECTIVES: To evaluate the efficacy of a new formulation of sucralfate as gel (Gastrogel) in the short-term prevention of gastroduodenal lesions in arthritic patients receiving nonsteroidal anti-inflammatory drugs. METHODS: One hundred seven patients with arthritis (M/F 18/89, mean age 55.2 +/- 9.7 yr) enrolled in two centers were considered eligible for the study if initial endoscopy showed the absence of any relevant mucosal damage. Patients were randomly allocated to receive diclofenac 200 mg/day or naproxen 1 g/day plus either sucralfate gel 1 g b.i.d. (N = 53) or identical placebo (N = 54) for 14 days in a randomized double-blind study. Repeated assessment of GI symptoms and endoscopy were performed at the end of the study period. RESULTS: At final endoscopy the incidence of erosion and the mean endoscopic score for both stomach and duodenum were significantly lower in the sucralfate gel group compared with placebo group (p < 0.05). Both heartburn and epigastric pain were significantly less frequent in patients receiving sucralfate gel than placebo (51 vs 30% and 49 vs 28% for heartburn and epigastric pain, respectively, p < 0.05). No differences were observed in the incidence or in the mean score for nausea. An unexplained difference in the incidence of ulcers was found between the two centers, but in both a similar reduction in the incidence of ulcers was observed between patients receiving sucralfate gel compared with those receiving placebo. The overall difference (8% in sucralfate-treated patients, 28% in patients receiving placebo) of gastroduodenal ulcers was statistically significant (p < 0.05). CONCLUSIONS: Sucralfate gel reduces both the incidence of acute gastroduodenal mucosal lesions and symptoms in patients with arthritis receiving short-term nonsteroidal anti-inflammatory drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Better quality of therapy with 5-ASA colonic foam in active ulcerative colitis. A multicenter comparative trial with 5-ASA enema.

We evaluated the efficacy, tolerance, and acceptance of a new 5-ASA colonic foam versus 5-ASA liquid enema in the short-term treatment of active ulcerative colitis in a three-week prospective, randomized, investigator-blind study, enrolling 233 patients from 12 outpatient clinics in Italy. In arm 1 of the study, 117 patients with mild attacks received 2 g of 5-ASA as foam or enema at bedtime. In arm 2, 116 patients with moderate attacks were given 4 g of 5-ASA as foam or enema at bedtime. End points were defined as complete relief of symptoms, and endoscopic and histological evidence of remission or improvement. In patients with mild relapse, 34 of 63 (54%) treated with foam were in clinical remission after only 10 days compared with 17 of 51 (31%) treated with enemas (P < 0.05). However, there was no statistically significant difference between foam (83%) and enema (74%) after three weeks. In patients with moderate relapse, a higher proportion of patients achieved complete clinical remission in the foam group (63%) compared with enema group (52%) after three weeks (difference 11%, 95% CI -7 to 29). No significant differences were observed in endoscopic and histological evaluation of colonic mucosa between treatment groups in either arm. 5-ASA foam was well tolerated. No unexpected adverse events were reported. Patient evaluation of therapy showed that foam was much better accepted than enema because foam was more comfortable, more practical, easier to retain, and interfered less with daily living.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Rectal↗
PubMed1993

Gastric retention of sucralfate gel and suspension in upper gastrointestinal diseases.

This study was designed to compare by scintigraphy the gastric retention of a new dosage form of sucralfate as gel (Gastrogel) with that of sucralfate suspension in 25 patients with upper gastrointestinal symptoms referred for routine endoscopy. After endoscopy 4 subgroups were defined: macroscopically normal mucosa (n = 7), antral gastritis and/or erosions (n = 6), gastric ulcer (n = 6) and duodenal ulcer (n = 6). Each patient received either sucralfate gel or sucralfate suspension in equivalent doses (5 ml containing 1 g sucralfate). Both formulations were labelled with 111 MBq 99mTc-DTPA before administration. The mean value of t1/2 in the total group was significantly longer when patients were taking sucralfate gel (61.6 min) compared to sucralfate suspension (33.8 min) (P < 0.001). The mean values of t1/2 were significantly longer for sucralfate gel compared to sucralfate suspension also among the subgroups (macroscopically normal P < 0.02, antral gastritis P < 0.05, gastric ulcer P < 0.02 and duodenal ulcer P < 0.05). After 2 and 3 hours, the percentage residual activity in the gastric area was significantly higher following administration of sucralfate gel compared to sucralfate suspension. This study has shown that, compared to sucralfate suspension, sucralfate gel persists longer in the stomach of patients with gastritis and peptic ulcer.

Adolescent↗
PubMed1993

Frontal hemisphere lateralization and depressive personality traits.

To assess the relationship between hemispheric differences in information processing and interhemispheric asymmetries in terms of brain bioelectrical activity, we correlated scores on the MMPI Depression scale with interhemispheric asymmetry, measured as peak amplitude and latency of the P3 component of somatosensory evoked potentials (SEPs) at the frontocortical region of 14 healthy unselected volunteers (8 men and 6 women) who were about to start a course in autogenic training. The sample was subdivided into two groups on the basis of the median score on the MMPI Depression scale. Subjects scoring above the median showed a right lateralization at the frontocentral region and a significantly shorter P3 latency at the right hemisphere compared to the left.

Adult↗