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C Dani

Publications and source records attributed to C Dani.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of the anti-adipogenic Hedgehog signaling pathway by cyclopamine does not trigger adipocyte differentiation.

Dysregulation of Hedgehog signaling can lead to several pathologies such as congenital defects and cancer. Here, we show that Hedgehog signaling is active in undifferentiated 3T3-L1 cells and decreases during adipocyte differentiation. Interestingly, this is paralleled by a decrease in Indian Hedgehog expression. We then tested if this down-regulation was sufficient to induce adipocyte differentiation. To this end, we demonstrate that the well-characterized Hedgehog inhibitor cyclopamine induced a decrease in Hedgehog signaling, similar to the one observed during adipocyte differentiation. However, cyclopamine did not induce nor potentiate adipocyte differentiation, as monitored by triglyceride staining and by the expression of several adipocyte markers: aP2, adipsin, C/EBPalpha, and Pref-1. Moreover, cyclopamine cannot substitute for other components of the differentiation medium: insulin, dexamethasone or IBMX. These results indicate that although Hedgehog signaling decreases during adipocyte differentiation, this down-regulation is not sufficient to trigger adipocyte differentiation. This suggests that Hedgehog signaling is an inadequate pharmacological target for patient suffering from syndromes associated with a decrease in fat mass, such as the ones observed in lipodystrophies.

1-Methyl-3-isobutylxanthine↗
PubMed2006

Adipose tissue-derived cells: from physiology to regenerative medicine.

During the last past years, the importance and the role of adipose tissues have been greatly expanded. After finding that adipose tissues are metabolically very active, the discovery of leptin moved the status of adipose tissue towards an endocrine tissue able to interact with all major organs via secretion of adipokines. Some years ago, the presence of adipocyte precursors, termed preadipocytes, has been described in all adipose tissue depots from various species of different age. More recently, the discovery that different phenotypes can be obtained from stroma cells of adipose tissue has largely emphazised the concept of adipose tissue plasticity. Therefore, raising great hope in regenerative medicine as adipose tissue can be easily harvested in adults it could represent an abundant source of therapeutic cells. Thus, adipose tissue plays the dual role of Mr Obese Hyde as a main actor of obesity and of Dr Regenerative Jekyll as a source of therapeutic cells. Adipose tissue has not yet revealed all its mysteries although one facet could not be well understood without the other one.

Adipose Tissue↗
PubMed2005

The human adipose tissue is a source of multipotent stem cells.

Multipotent stem cells constitute an unlimited source of differentiated cells that could be used in pharmacological studies and in medicine. Recently, several publications have reported that adipose tissue contains a population of cells able to differentiate into different cell types including adipocytes, osteoblasts, myoblasts, and chondroblasts. More recently, stem cells with a multi-lineage potential at the single cell level have been isolated from human adipose tissue. These cells, called human Multipotent Adipose-Derived Stem (hMADS) cells, have been established in culture and interestingly, maintain their characteristics with long-term passaging. The adipocyte differentiation of hMADS cells has been thoroughly studied and differentiated cells exhibit the unique feature of human adipocytes. Finally, potential applications of stem cells isolated from adipose tissue in medicine will be discussed.

Adipocytes↗
PubMed2004

Cloning of hOST-PTP: the only example of a protein-tyrosine-phosphatase the function of which has been lost between rodent and human.

Protein-tyrosine-phosphatases (PTP-ases), in concert with protein tyrosine kinases, control various biological activities such as cell growth and differentiation. In rodents, around 40 PTP-ases have been described. Functional orthologue for each of these PTP-ases have been identified in human, except for OST-PTP. OST-PTP is a transmembrane PTP-ase with a restricted tissue distribution. In silico analysis on public sequence databases reveals a human OST-PTP gene orthologue that encompasses 21 kb on chromosome 1q32.1. Using RT-PCR we isolated a 4 kb hOST-PTP transcript. hOST-PTP cDNA sequence exhibits numerous disablements indicating that it does not code for a PTP-ase but is rather a pseudogene with unique features. Indeed, (i) it has no "functional" parent in the human genome, (ii) it has retained an "intron-exon" structure, and (iii) it is transcribed in a regulated manner. Interestingly, we found two ESTs, from domesticated pig and from cow that exhibit ORF that would predict a functional OST-PTP orthologue in Artiodactyls. Taken together, these results indicate that OST-PTP is the only PTP-ase the function of which has been lost during the evolution process between rodents and human.

Amino Acid Sequence↗
PubMed2004

Prediction of early tolerance to enteral feeding by measurement of superior mesenteric artery blood flow velocity: appropriate- versus small-for-gestational-age preterm infants.

AIM: To evaluate whether serial Doppler measurements of superior mesenteric artery blood flow velocity could predict early tolerance to enteral feeding in preterm infants. METHODS: In a prospective study, 54 healthy preterm neonates were assigned to one of the following groups: neonates with birthweight appropriate for gestational age (group 1), neonates small for gestational age without (group 2) and with prenatal haemodynamic disturbances (group 3). We studied Doppler blood flow velocity and resistance index before and after the first feed. RESULTS: Contrary to patients of group 3, infants in groups 1 and 2 showed a significant increase in blood flow velocity and a significant decrease in resistance index from the preprandial values after the first feed. At each postprandial time, we found significant differences in all velocity and resistance measurements between patients of group 3 and patients of both groups 1 and 2. In all patients, we found that the value of mean velocity measured 30 min after the first feed was the most predictive of early feed tolerance, with 95% sensitivity and 94% specificity when mean velocity >0.38 m/s. CONCLUSION: Small-for-gestational-age preterm infants with prenatal haemodynamic disturbances have an unusual intestinal haemodynamic response to the first feed. In the whole group of preterm infants, the value of mean velocity measured 30 min after the first feed is a good tool for the clinician in predicting early enteral feeding.

Blood Flow Velocity↗
PubMed2004

Effect of blood transfusions on oxidative stress in preterm infants.

OBJECTIVE: To confirm the increase in non-transferrin bound iron (NTBI) after packed red cell (PRC) transfusion and to evaluate the association with increased oxidative stress in preterm infants. METHOD: Twenty healthy preterm infants (gestational age 28.2 (2.2) weeks; birth weight 1047 (230) g), who required blood transfusion for anaemia of prematurity were prospectively studied. Serum concentrations of NTBI, total hydroperoxides (TH), and protein SH groups, and plasma total radical trapping antioxidant capability (TAC) were measured within three hours before and after PRC transfusion. The infants were transfused with 38.6 (23) ml PRCs over 5.8 (1.0) hours, at a mean age of 43.3 (25.1) days. RESULTS: After PRC transfusion, haemoglobin concentration increased from 9.2 (1.1) to 14.6 (1.5) g/l. Mean plasma NTBI concentration after transfusion was significantly higher (0.43 (0.45) v 2.03 (1.31) micromol/l; p = 0.001), while plasma concentrations of TH (212.3 (42.2) v 214.7 (66.3) Carr units/l) and protein SH groups (317.5 (38.8) v 353.8 (57.4) micromol/), and TAC (256.3 (36.1) v 267.1 (42.4) micromol HClO/ml) remained unchanged. CONCLUSION: For three hours after PRC transfusion, plasma NTBI is significantly increased in preterm infants, but this is not associated with significant changes in oxidative stress.

Antioxidants↗
PubMed2004

Role of oxidative stress as physiopathologic factor in the preterm infant.

Oxidative stress usually occurs when the production of damaging free radicals (ROS) and other oxidative molecules exceeds the capacity of the body's antioxidant defenses. This process is supposed to begin after the delivery, but it can even affect the fetus when maternal pregnancy diseases (i.e.: pre-eclampsia, eclampsia, maternal infections) occur and in the case of preterm delivery. Most living organisms have developed well integrated antioxidant defenses to prevent the potential negative role of the ROS, in order to scavenge them and to control their concentration. These mechanisms are deficient in preterm newborn. Many illnesses in preterm infants, including bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), brain injury such as hypoxic/ischemic encephalopathy, and intraventricular hemorrhage (IVH) are thought to be related to the action of ROS. This presumably occurs due to the fact that the antioxidant system of preterm infants is at the same time highly stressed and incompletely developed. Unfortunately, the clinical trials which tried to prevent oxidative stress using antioxidant agents failed their objective and therefore they cannot be considered as an effective therapy. The objective of this review is to clarify the role of oxidative stress in the development of the previous severe diseases in preterm infants, and its possible correlation with hyperbilirubemia.

Bronchopulmonary Dysplasia↗
PubMed2003

Redox status in very-low birth-weight newborns.

Inborn metabolic diseases, such as disorders in pyruvate metabolism, in gluconeogenesis or in the respiratory chain, may present with lactic acidosis in newborn infants. A simple tool to screen for the efficacy of mitochondrial oxidation reduction activity is the detection of the redox status through simultaneous measurements of plasma lactate, pyruvate and ketone bodies, which are strongly influenced by feeding and stress. We present the redox status values of 55 very-low birth-weight infants under different nutritional conditions. We were able to demonstrate that the redox status values are not dependent on the type of nutrition (oral feeding or continuous enteral nutrition). Instead we observed a strong difference between newborns with intrauterine growth retardation and newborns with appropriate growth. Newborns with intrauterine growth retardation show lower preprandial values of glucose and ketone bodies than newborns with appropriate weight, but higher levels of lactate and pyruvate; nevertheless the lactate/pyruvate and beta-hydroxybutyrate/acetoacetate ratios are normal. The results of the redox status study could suggest the reduced activity of gluconeogenesis and, probably, of beta-oxidation in very-low birth-weight newborns with intrauterine growth retardation.

3-Hydroxybutyric Acid↗
PubMed2003

Perfluorocarbons attenuate oxidative lung damage.

The aim of this study was to investigate the effect of tidal liquid ventilation (TLV) compared to conventional mechanical ventilation (CMV) on oxidative lung damage in the setting of acute respiratory distress syndrome (ARDS). After repeated lung lavages, 10 minipigs were treated with CMV or TLV for 4 hr before the animals were sacrificed. Samples for blood gas analysis and bronchial aspirate samples were withdrawn before the induction of lung injury, and at 10 min, 2 hr, and 4 hr after the beginning of ventilatory support. To assess lung oxidative damage, total hydroperoxide (TH) and advanced oxidation protein product (AOPP) concentrations were measured in bronchial aspirate samples. After 2 and 4 hr of ventilatory support, partial oxygen tension (PaO(2)) and base excess (BE) were significantly higher in the TLV group than in the CMV group, while PaCO(2) was slightly higher, but with no statistical significance. In the CMV group, the AOPP level was significantly higher at 4 hr than at baseline. TH and AOPP bronchial aspirate concentrations were higher in the CMV group than in the TLV group at 2 and 4 hr of ventilation. We conclude that animals treated with TLV showed lower oxidative lung damage compared to animals treated with CMV.

Animals↗
PubMed2003

Plasma bilirubin level and oxidative stress in preterm infants.

OBJECTIVE: To assess the hypothesis that changes in plasma total bilirubin levels (Btot) can influence the antioxidant system and oxidative stress in preterm infants. METHODS: Twenty two healthy preterm infants who presented with visible non-haemolytic hyperbilirubinaemia were studied at the mean (SD) age of 3.7 (1.5) days. Btot, plasma total hydroperoxide concentration (TH), plasma protein SH group concentration, and total antioxidant capacity of the plasma (TAC) were measured at study entry and after 24 hours. RESULTS: Btot did not correlate with TH, TAC, or protein SH group concentration, but a significant correlation was found between TH and TAC, TH and protein SH groups, and TAC and protein SH groups, both at study entry and after 24 hours. CONCLUSION: The decrease in plasma bilirubin was contemporary with an increase in plasma antioxidant capacity and decrease in oxidative stress in preterm infants. This may be the result of the pro-oxidant effect of haem oxygenase, mediated by iron release, which may outcompete the antioxidant properties of bilirubin.

Antioxidants↗
PubMed2002

PPARgamma-dependent and PPARgamma-independent effects on the development of adipose cells from embryonic stem cells.

Peroxisome proliferator-activated receptor (PPAR) gamma was shown to be required for adipocyte formation both in vivo and in vitro. However, the role of PPARgamma in the initial steps of adipose cell development was not distinguished from its role in the terminal steps. We now show that PPARgamma is expressed early in embryoid bodies (EBs) derived from embryonic stem cells and in E.8.5 mouse embryos. Addition of a specific ligand for PPARgamma in developing EBs over-expressing PPARgamma did not commit stem cells towards the adipose lineage. In differentiated PPARgamma(-/-) EBs, only markers characteristic of preadipocytes were found to be expressed. PPARdelta is present in EBs but did not compensate for the lack of PPARgamma in terminal differentiation. Taken together, these results favor a critical PPARgamma-independent phase culminating in preadipocyte formation that precedes a PPARgamma-dependent phase in the development of adipose cells from pluripotent stem cells.

Adipocytes↗
PubMed2002

Effect of blood transfusions on cerebral haemodynamics in preterm infants.

AIM: To assess the possible cerebral haemodynamic changes occurring in preterm infants after blood transfusions. METHODS: Preterm infants who had undergone blood transfusions were prospectively studied using both near infrared spectroscopy and cerebral Doppler ultrasonography. RESULTS: Fourteen infants (mean gestational age 29.6 wk, SD 2.6; mean birthweight 1,430g, SD 332) were studied at the mean age of 29 (SD 14) d. A significant increase in oxygenated haemoglobin (O2Hb), deoxygenated haemoglobin (HHb), mixed cerebral oxygen saturation (SmO2) and change in cerebral blood volume occurred after transfusion. Between ultrasound parameters, we found a decrease in diastolic velocity and an increase in resistance index. CONCLUSION: Blood transfusions improve cerebral oxygen supply and induce a decrease in cerebral blood volume, probably due to an increase in cerebral vessel resistance.

Anemia↗
PubMed2002

Haemodynamic changes in the brain after vaginal delivery and caesarean section in healthy term infants.

OBJECTIVE: To investigate whether the mode of delivery may affect neonatal cerebral haemodynamics during the first hour of life. DESIGN: Prospective study. SAMPLE: Healthy infants with gestational age > or =37 weeks and birthweight appropriate for gestational age, born after uncomplicated pregnancy by vaginal delivery or elective caesarean section, two to five hours after the delivery. METHODS: Near infra-red spectroscopy was used to measure changes of oxygenated haemoglobin, deoxygenated haemoglobin, oxidized-reduced cytochrome aa3, and mean cerebral oxygen saturation (mixed cerebral oxygen saturation = oxygenated haemoglobin/total haemoglobin). Changes in cerebral blood volume were calculated. RESULTS: Near infra-red spectroscopy data did not show significant differences between infants born by vaginal delivery or by caesarean section. There was a significant decrease of oxygenated haemoglobin and change of cerebral blood volume values at 120 and 180 minutes in both the groups, while deoxygenated haemoglobin and oxidized-reduced cytochrome aa3 were unchanged. CONCLUSIONS: A decrease of cerebral blood volume occurs after birth and this occurs both in infants born by vaginal delivery and by caesarean section.

Blood Pressure↗
PubMed2002

Pharmacokinetics of oxatomide in preterm infants.

The pharmacokinetics and tolerability of oxatomide oral suspension were investigated in preterm infants to evaluate the feasibility of planning a further study to assess its antiinflammatory effects and its effectiveness in preventing chronic lung disease (CLD). Following the administration of oxatomide 1 mg/kg, the peak plasma concentration (Cmax), the elimination half-life (t1/2), the volume of distribution (Vd), and the area under the curve (AUC) 0-36 h were measured and the following results were obtained: 42.2 +/- 15 ng/ml at 2 h after oxatomide administration, 41.4 +/- 2.0 h, 37.4 +/- 4.2 l/kg, and 468 +/- 52 ng/ml/h, respectively. Our study, therefore, demonstrated that a dose of 1 mg/kg/day oxatomide was effective in reaching therapeutic plasma levels in preterm infants without inducing adverse effects.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Inhibition of myogenesis enables adipogenic trans-differentiation in the C2C12 myogenic cell line.

C2C12 cells are a well-established model system for studying myogenesis. We examined whether inhibiting the process of myogenesis via expression of dominant negative (DN) mitogen-activated protein kinase kinase-3 (MKK3) facilitated the trans-differentiation of these cells into adipocytes. Cells expressing DN MKK3 respond to rosiglitazone, resulting in adipocyte formation. The effects of rosiglitazone appear to be potentiated through peroxisome proliferator activating receptor-gamma. This trans-differentiation is inhibited by the use of the phosphoinositide-3 (PI3) kinase inhibitor, LY294002. These results indicate that preventing myogenesis through expression of DN MKK3 facilitates adipocytic trans-differentiation, and involves PI3 kinase signalling.

Adipocytes↗
PubMed2001

Combined regimen of cisplatin, doxorubicin, and alpha-2b interferon in the treatment of advanced malignant pleural mesothelioma: a Phase II multicenter trial of the Italian Group on Rare Tumors (GITR) and the Italian Lung Cancer Task Force (FONICAP).

BACKGROUND: The cisplatin-doxorubicin combination has shown moderate activity in malignant pleural mesothelioma (MPM; objective response, 25%), and preclinical studies suggest that interferons (IFNs) may have an antiproliferative effect on mesothelioma cell lines with a marked increase in cisplatin cytotoxicity. Therefore, the combined chemoimmunotherapy regimen is an worthwhile approach to evaluate in a Phase II trial. METHODS: From December 1995 to June 1999, 37 previously untreated patients with MPM were treated with cisplatin 60 mg/m(2) intravenously on Day 1 plus doxorubicin 60 mg/m(2), recycled every 3-4 weeks and IFN-alpha-2b, 3 x 10((6)) international units subcutaneously 3 times a week for a total of 6 courses or until progression. Inclusion criteria were histologic diagnosis of MPM and measurable disease defined by computed tomography scan or magnetic resonance imaging. RESULTS: Thirty-four patients were assessable for toxicity and 35 for efficacy according to World Health Organization criteria. One hundred thirty-five courses were administered with a median of 4 cycles per patients. Seventy-six percent of patient presented at least 1 episode of severe myelosuppression (Grade 3 and 4). Severe anemia and thrombocytopenia occurred in 30% and 24% of patients, respectively. Sixty percent of patients presented constitutional symptoms. In the 35 patients assessable for response, the overall response rate was 29% (95% confidence interval, 15-47%). The median duration of response was 8.4 months. With a median follow-up of 19.6 months, the median survival was 9.3 months. One- and 2-year survival was 45% and 34%, respectively. CONCLUSIONS: This combined regimen has definite activity in MPM. However, toxicity, particularly myelosuppression and fatigue, is not negligible and may limit its application.

Adult↗
PubMed2001

Compactin enhances osteogenesis in murine embryonic stem cells.

Embryonic stem (ES) cells have the capacity to differentiate into various cell types in vitro. In this study, we show that retinoic acid is important for the commitment of ES cells into osteoblasts. Culturing retinoic acid treated ES cells in the presence of the osteogenic supplements ascorbic acid and beta-glycerophosphate resulted in the expression of several osteoblast marker genes, osteocalcin, alkaline phosphatase, and osteopontin. However, there was only a slight amount of mineralized matrix secretion. Addition of bone morphogenic protein-2 or compactin, a drug of the statin family of HMG-CoA reductase inhibitors, resulted in a greatly enhanced formation of bone nodules. Compactin did not modify the expression of osteogenic markers, but at the late stage of differentiation promoted an increase in BMP-2 expression. These results establish ES-cell derived osteogenesis as an effective model system to study the molecular mechanisms by which the statin compactin promotes osteoblastic differentiation and bone nodule formation.

Alkaline Phosphatase↗