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Biomedical subjects

C Cosentino

Publications and source records attributed to C Cosentino.

At least 19 recordsLinked to original sources
PubMed2006

The p85 regulatory subunit of PI3K mediates TSH-cAMP-PKA growth and survival signals.

Phosphatidylinositol 3-kinase (PI3K) is necessary for thyroid stimulating hormone (TSH)-induced cell cycle progression. To determine the molecular mechanism linking PI3K to TSH, we have identified a serine residue in p85alpha(PI3K) phosphorylated by protein kinase A (PKA) in vitro and in vivo. Expression of an alanine mutant (p85A) abolished cyclic AMP/TSH-induced cell cycle progression and was lethal in thyroid cells (FRTL-5). The aspartic version of the p85alpha(PI3K) (p85D) inhibited apoptosis following TSH withdrawal. The p85alpha(PI3K) wild type not the p85A bound PKA regulatory subunit RIIbeta in cells stimulated with cAMP or TSH. The binding of the aspartic version of p85alpha(PI3K) to RIIbeta was independent of cAMP or TSH stimulation. Similarly, binding of PI3K to p21Ras and activation of AKT, a downstream PI3K target, were severely impaired in cells expressing the p85A mutant. Finally, we found that the catalytic activity of PI3K was stimulated by TSH in cells expressing the wild-type p85alpha(PI3K) but not in cells expressing p85A. This latter mutant did not affect the epidermal growth factor-stimulated PI3K activity. We suggest that (1) TSH-cAMP-induced PKA phosphorylates p85alpha(PI3K) at serine 83, (2) phosphorylated p85alpha(PI3K) binds RIIbeta-PKA and targets PKAII to the membrane, and (3) PI3K activity and p21Ras binding to PI3K increase and activate PI3K downstream targets. This pathway is essential for the transmission of TSH-cAMP growth signals.

Animals↗
PubMed2006

p85 regulatory subunit of PI3K mediates cAMP-PKA and estrogens biological effects on growth and survival.

Cyclic adenosine 3'5' monophosphate (cAMP) and protein kinase A (PKA) cooperate with phosphatidylinositol 3' kinase (PI3K) signals in the control of growth and survival. To determine the molecular mechanism(s) involved, we identified and mutagenized a specific serine (residue 83) in p85alpha(PI3K), which is phosphorylated in vivo and in vitro by PKA. Expression of p85alpha(PI3K) mutants (alanine or aspartic substitutions) significantly altered the biological responses of the cells to cAMP. cAMP protection from anoikis was reduced in cells expressing the alanine version p85alpha(PI3K). These cells did not arrest in G1 in the presence of cAMP, whereas cells expressing the aspartic mutant p85D accumulated in G1 even in the absence of cAMP. S phase was still efficiently inhibited by cAMP in cells expressing both mutants. The binding of PI3K to Ras p21 was greatly reduced in cells expressing p85A in the presence or absence of cAMP. Conversely, expression of the aspartic mutant stimulated robustly the binding of PI3K to p21 Ras in the presence of cAMP. Mutation in the Ser 83 inhibited cAMP, but not PDGF stimulation of PI3K. Conversely, the p85D aspartic mutant amplified cAMP stimulation of PI3K activity. Phosphorylation of Ser 83 by cAMP-PKA in p85alpha(PI3K) was also necessary for estrogen signaling as expression of p85A or p85D mutants inhibited or amplified, respectively, the binding of estrogen receptor to p85alpha and AKT phosphorylation induced by estrogens. The data presented indicate that: (1) phosphorylation of Ser 83 in p85alpha(PI3K) is critical for cAMP-PKA induced G1 arrest and survival in mouse 3T3 fibroblasts; (2) this site is necessary for amplification of estrogen signals by cAMP-PKA and related receptors. Finally, these data suggest a general mechanism of PI3K regulation by cAMP, operating in various cell types and under different conditions.

Animals↗
PubMed2005

Impact of children's respiratory allergies on caregivers.

BACKGROUND: Despite the great attention that has been paid to HRQoL in children with respiratory allergy, few studies have addressed this aspect in relation to caregivers. The aim of our study was to evaluate the impact of childhood respiratory allergies on caregivers by means of a new method. METHODS: 119 parents of children suffering from allergies (75 suffering from asthma and 44 suffering from rhinitis) were recruited from three Italian Allergy Units. Parents were asked to complete the Disease Impact On Caregiver (DIOC), a new non disease specific questionnaire, validated on the Italian population. The questionnaire consists of 31 items grouped in four factors (Performance, Personal gratification, Psychophysical endurance, Socio-emotional domain) and covers the life aspects that could be affected by the assistance duties towards an ill family member. RESULTS: Child's asthma resulted to have a worse impact on many aspects of a parents' life than rhinitis. Differences resulted to be statistically significant in 19 aspects out of the 31 assessed. The worse impact of asthma versus rhinitis was confirmed in the following domains: Performance (24.0 +/- 18.2 vs 11.5 +/- 17.8), Personal gratification (26.3 +/- 20.5 vs 12.1 +/- 16.5) and Psychophysical endurance (35.0 +/- 24.8 vs 18.8 +/- 21.7). In the Socio-emotional domain no difference emerged. CONCLUSIONS: Compared to parents of rhinitics, parents of asthmatic children appear to be more compromised in their resistance to stress, mood, emotional stability, amount of spare time and leisure activities. Our results suggest the need of giving the due attention to these problems both in clinical practice and in research, in order to avoid possible interferences of the caregiver's distress in the optimization of treatment outcome.

Adult↗
PubMed2004

Inhibition of phosphatidylinositol 3-kinase amplifies TEGDMA-induced apoptosis in primary human pulp cells.

Cytotoxicity of triethylene glycol dimethacrylate (TEGDMA), a co-monomer of dental resinous restorative materials, is firmly established in vitro, but the molecular mechanisms are unknown. Here we examined apoptosis and necrosis induced by TEGDMA in human primary pulp cells. The levels of apoptotic and necrotic cell populations differentially increased after exposure to increasing concentrations of TEGDMA. A two-fold increase in the percentage of apoptotic cells was induced by 1 mmol/L TEGDMA. However, a population shift among cells in apoptosis and necrosis was detected when cell cultures were exposed to 2 mmol/L TEGDMA. Inhibition of the MAP Kinase/ERK pathway had no influence on cell survival, but inhibition of phosphatidylinositol 3 kinase (PI3-Kinase; Akt/protein kinase B) by LY294002 amplified TEGDMA-induced apoptosis. Moreover, Akt phosphorylation was inhibited in the presence of TEGDMA. These results suggest that depression of PI3K signaling may be a primary target in TEGDMA-induced apoptosis.

Apoptosis↗
PubMed2003

Intraabdominal abscess following open and laparoscopic appendectomy in the pediatric population.

BACKGROUND: Studies comparing intraabdominal abscess (IAA) rates following laparoscopic appendectomy (LA) and open appendectomy (OA) have shown conflicting results. METHODS: The charts of 324 children undergoing appendectomy were reviewed retrospectively to examine the incidence of IAA. RESULTS: Of the 324 appendectomies, 204 (63.0%) were completed laparoscopically and 119 (36.7%) were performed open. The conversion rate was 0.2% (1/324). Of the 15 (4.6%) IAAs, 7 occurred in the LA group (3.4%) and 8 occurred in the OA group (6.7%) [p = not significant (NS)]. The incidence of IAA for perforated appendicitis for LA was 15% (7/46) and that for OA was 10% (7/70) (p = NS). CONCLUSION: This study demonstrates no statistically significant difference in the rate of IAA among children following LA and OA. LA can be performed for perforated appendicitis without increasing the risk of IAA.

Abdominal Abscess↗
PubMed2003

Sensitization to food or inhalant allergens in pediatric patients. Clinical usefulness of first-level panel tests for specific IgE.

First-level in vitro diagnostic tests for specific IgE against common inhalant or food allergens have been used to identify allergic patients. We evaluated the performance of Phadiatop and Fx5 (mixed food allergens) serological tests (Pharmacia Diagnostics AB, Uppsala, Sweden) in different groups of pediatric patients. We studied two groups of pediatric patients: 61 children recruited from an Allergy and Clinical Immunology Unit (Group 1); 136 children from a Pediatric Unit not specifically devoted to allergic diseases (Group 2); the two groups comprised patients with (A) or without (B) clinical suspicion of allergic disease. Sera were collected from routine blood analysis. Frequencies of positivities for Phadiatop and/or Fx5 were very high (68.8%) in Group 1, however, as many as 35.5% of Group 2 children were positive, as well. All the patients of Group 1 with clinical suspicion of allergic disease (1A), confirmed by allergologic diagnostic tests, had a positive first-level test; 42.8% only of the patients in Group 2 with suspicion of allergic disease (2A) had a positive first-level test. None of the Phadiatop/Fx5-negative children of Group 2A had specific-IgE with conventional tests. In 30% of children not suspected for allergic diseases (1B and 2B), positive first-level tests were observed. Such unexpected positivities were confirmed by single specific-IgE assays in 94.7% (for inhalants) or 71% (for foods) of cases. In conclusion, altogether the sensitivity and overall performance of first-level tests in pediatric populations (especially for inhalant allergens) may suggest their use, under appropriate circumstances, both as a first diagnostic approach (to rule out negative patients) and for screening purposes.

Administration, Inhalation↗
PubMed2002

Cytokine pattern in allergic and non-allergic chronic rhinosinusitis in asthmatic children.

BACKGROUND: Rhinosinusitis represents one of the most common chronic diseases. The association of rhinosinusitis with asthma has been frequently reported. Eosinophils and Th2 cells play a pathogenic mechanism in asthma. OBJECTIVE: The aims of the study were to evaluate the cytokine pattern in chronic rhinosinusitis in asthmatic children and to compare the findings in allergic vs. non-allergic asthmatics. METHODS: Thirty-five asthmatic children were evaluated, 19 males and 16 females, with an average age of 8.7 years. All children were asthmatic and suffered from chronic rhinosinusitis. Twenty were allergic and 15 were non-allergic. Ten healthy children were studied as normal controls. Evaluated parameters were the levels of the following cytokines: IL-1beta, IL-4, IL-6, IL-8, IL-12, IFN-gamma and TNF-alpha. Cytokines were recovered from rhinosinusal lavage and measured by immunoassays. Nasal cytology was also performed in all subjects and inflammatory cells were counted by conventional staining. RESULTS: Allergic subjects showed a significant increase of IL-4 (P < 0.01) and TNF-alpha (P < 0.05) and a significant decrease of IL-12 (P < 0.05) and of IFN-gamma (P < 0.0001), whereas IL-1beta, IL-6 and IL-8 were not significantly increased. Non-allergic children showed a significant increase of IL-4 (P < 0.05) and a significant decrease of IFN-gamma (P < 0.0001), IL-12 was not significantly decreased, and IL-1beta, IL-6 and IL-8 were not significantly increased. A significant inflammatory infiltrate was present in all asthmatic children. Significant correlations were demonstrated between IL-4 and IL-12 (P < 0.001), IL-12 and IFN-gamma (P < 0.001), IL-8 and neutrophils (P < 0.01), and TNF-alpha and monocytes/macrophages (P < 0.05), in allergic asthmatics. IL-4 and IL-12 were significantly correlated (P < 0.05) as well as IL-8 and neutrophils (P < 0.01) in non-allergic asthmatics. CONCLUSION: This study shows that allergic asthmatic children with chronic rhinosinusitis have a typical Th2 cytokine pattern, but also non-allergic asthmatic children share a similar pattern. These findings would suggest the existence of a common pathophysiological mechanism shared by upper and lower airways and are consistent with the concept of united airways disease.

Asthma↗
PubMed2001

Fexofenadine reduces nasal congestion in perennial allergic rhinitis.

BACKGROUND: Nasal congestion is the predominant symptom in perennial allergic rhinitis (PAR), and it seems to be mainly related to the late-phase inflammatory events. The present pilot study aimed to evaluate the therapeutic effect exerted by fexofenadine in patients with PAR due to mite allergy. METHODS: This study was a parallel, double-blind, randomized, three-arm (1:1:1), placebo-controlled study. Thirty-one subjects with PAR were enrolled and received double-blind medication: fexofenadine 120 or 180 mg, or placebo, once a day for 28 days. RESULTS: The total symptom score was reduced by fexofenadine (both dosages) at V2 (P=0.007), whereas placebo did not modify it. Nasal congestion decreased after 1 week of treatment with fexofenadine 120 (P=0.027) and 180 (P=0.01), but not with placebo (P=NS). At V3, fexofenadine (both dosages) significantly reduced nasal congestion (P=0.011 and P=0.007, respectively), by placebo did not show any significant effect. CONCLUSIONS: This pilot study represents the first evidence of the efficacy of fexofenadine in PAR, and also the control of the nasal congestion. We suggest performing larger trials to confirm these preliminary findings.

Adolescent↗
PubMed2000

Effect of substitution pattern on 1H, 13C NMR chemical shifts and 1J(CH) coupling constants in heparin derivatives.

1H, 13C NMR chemical shifts and 1J(CH) coupling constants were measured for derivatives of heparin containing various sulfation patterns. 1H and 13C chemical shifts varied considerably after introducing electronegative sulfate groups. Chemical shifts of protons linked to carbons changed by up to 1 ppm on substitution with O- and N-sulfate or acetyl groups. Differences up to 10 ppm were detected for 13C chemical shifts in substituted glucosamine, but a less clear dependence was found in iduronate. 1J(CH) values formed two groups, corresponding to either sulfation or non-sulfation at positions 2 and 3 of glucosamine. O-sulfation caused increases up to 6 Hz in 1J(CH) and N-sulfation decreases up to 4 Hz. N-acetylation gave similar 1J(CH) values to N-sulfation. At positions 2 and 3 of iduronate the trend was less marked; 1J(CH) for O-sulfated positions usually increasing. Introduction of sulfate groups influences chemical shift and 1J(CH) values at the position of substitution, but also at more remote positions. 1J(CH) at the glycosidic linkage positions varied between free-amino and N-sulfated compounds, by up to 9 Hz. These results and changes in chemical shift values suggest that iduronate residues and the glycosidic linkages are affected, indicating overall conformational change. This may have important implications for biological activities.

Acetylation↗
PubMed2000

Tourette's syndrome and neurofibromatosis type 1.

The case of an 11-year-old male with clinical features compatible with a diagnosis of Tourette's syndrome and neurofibromatosis type 1 is reported. Magnetic resonance imaging revealed bilateral pallidal hyperintensities, which may be related to the tic disorder.

Child↗
PubMed1998

Solid state NMR spectroscopy study of molecular motion in cyclomaltoheptaose (beta-cyclodextrin) crosslinked with epichlorohydrin.

Dry and hydrated insoluble cyclomaltoheptaose (beta-cyclodextrin, beta-CD) polymers have been investigated by solid state 13C NMR spectroscopy techniques such as cross polarization/magic angle spinning with dipolar decoupling (CP/MAS), magic angle spinning both with (DD-MAS) and without (MAS) dipolar decoupling and CP/MAS dipolar dephasing (dd-CP/MAS) to allow the assignment of the main 13C signals. In the solid state, the presence of water in the samples resulted in a better resolution reflecting increased mobility. Two distinct components (crosslinked beta-CD and polymerized epichlorohydrin) have been found. The molecular mobility of these two components has been analyzed in terms of relaxation parameters such as 13C spin lattice relaxation (T1) and 1H spin lattice relaxation in the rotating frame (T1 rho). The T1 values of the polymers show that the beta-CD trapped inside the polymers does not seem to undergo changes in its mobility whatever the amount of epichlorohydrin. The addition of water to beta-CD significantly increases the T1 values reflecting strong interaction between beta-CD and the solvent. The T1P values obtained reflect the homogeneous nature of the materials.

Carbohydrate Sequence↗
PubMed1991

Pediatric falls from heights.

Injuries resulting from falls from heights still constitute a significant portion of urban trauma. At this pediatric trauma center, 70 children were admitted from 1985 to 1988 after sustaining a fall of 10 feet or greater or at least one story. The mean patient age was 5 years and 68% of the patients were boys. Seventy-eight percent of falls occurred from 2 stories or less and usually took place at or near the home. Most patients sustained a single major injury and all survived. The majority of injuries involved the head or skeleton and residual functional deficits were uncommon. The incidence of falls from heights has remained high in urban areas despite public education and building codes that require window guards and safety rails.

Accidental Falls↗
PubMed1988

Canine model for surgical correction of chronic venous hypertension.

A chronic model of venous hypertension was created by iliofemoral venous ligation in the left hindlimb of eight greyhounds (right limb control). Prior to ligation, immediately postligation (T0), and at 2, 4, 6, and 15 weeks postligation (T2-T15), bilateral hindlimb venous pressures were measured at rest. At T2-T15, exercise pressures were measured for 5 min after hindlimb muscle contraction induced under sedation by tetanic (20 sec, 50 Hz, 8 mA) stimulus (S30-S300 sec). Resting and exercise pressures were significantly higher in the ligated hindlimb at all time intervals (resting, P less than 0.001 at T0, T2, T4, T6, and P less than 0.025 at T15; exercise, P less than 0.001 for S30-S300 at T2-T15). In five of the animals at 15 weeks, a cross-femoral venous bypass (CFB) with adjacent adjuvant arteriovenous fistula (AVF) was constructed using autologous external jugular vein. Venous pressures were measured at 2 and 6 weeks post-CFB both at rest and after tetanic muscle stimulation. At 2 weeks, venous pressure in the ligated limb was significantly higher than that in control only after exercise (P less than 0.025 at S30-S120; P less than 0.05 at S150-S180; NS at S240-S300). At 6 weeks, venous pressures were not significantly different at rest or with exercise. All five grafts were patent at 6 weeks. Three of five dogs then successfully underwent ligation of the AVF. At 2 weeks post-AVF ligation there was no difference in resting or exercise venous pressure in the ligated limb compared to control. At 6 weeks post-AVF ligation only two dogs remained for monitoring and in these there was no trend toward venous hypertension in the ligated hindlimb. Graft patency was maintained despite AVF ligation.

Animals↗
PubMed1988

Hemodynamics of revascularization for iliofemoral venous occlusion: a short-term canine model.

A short-term canine model of lower extremity venous hypertension was created to study the hemodynamics of crossfemoral venous bypass grafts (CFB). Specifically, the hemodynamic effects of bypass conduit diameter and adjunctive arteriovenous fistulas (AVFs) were investigated. Unilateral hind limb venous hypertension was produced by iliofemoral venous ligation in six groups of five greyhounds each. Group I had venous ligation alone. CFBs were constructed in the remaining five groups: group II, 3 mm bypass conduit alone; group III, 3 mm bypass plus sequential AVF; group IV, 3 mm bypass plus caudad AVF; group V, 3 mm bypass plus cephalad AVF; group VI, 6 mm bypass conduit alone. Venous hypertension was significantly reduced by CFB (group II, p less than 0.025; group VI, p less than 0.001); increasing the diameter of the bypass conduit from 3 to 6 mm produced significantly greater graft flow (p less than 0.05), while completely relieving venous hypertension. Addition of adjunctive AVFs significantly augmented graft flow (p less than 0.001) but tended to aggravate ipsilateral venous hypertension (group III, p less than 0.01; group IV increase, NSS; group V, p less than 0.001). During the 4 hours of pressure monitoring, venous hypertension diminished significantly (p less than 0.05) with the sequential AVF but not with the other AVF. We conclude that (1) AVFs may be required for adequate graft flow if a small-diameter (3 mm) bypass conduit is used to relieve venous hypertension; (2) adjunctive AVFs aggravate venous hypertension; (3) sequential AVFs seem to be the most hemodynamically efficacious; (4) AVFs may not be necessary if a large, isodiametric (6 mm) conduit is used.

Anastomosis, Surgical↗
PubMed1984

[Alkyl and aryl derivatives of isoquinoline. II. Synthesis and pharmacologic activity of dialkylaminoalkyl esters of 1-chloro-3-carboxy-4-methylisoquinoline and the corresponding 4-phenyl derivative].

The synthesis of a series of dialkylaminoalkylic esters of 1-chloro-3-carboxy-4-methylisoquinoline and of 1-chloro-3-carboxy-4-phenylisoquinoline is described. The pharmacological activity of some of these compounds was studied. The morpholinoethylester of 1-chloro-3-carboxy-4-methylisoquinoline (VIIa), dimethylaminoethylester (VIIb) and diethylaminoethylester (VIIc) showed a good antispasmodic activity. 4-Phenyl-derivatives (XVa), (XVb), (XVc) were more active than analogous 4-methyl derivatives; particularly the diethylaminoethylester of 1-chloro-3-carboxy-4-phenylisoquinoline (XVc) showed an antagonist effect against spasmogens similar to that of papaverine.

Acetylcholine↗