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Biomedical subjects

L Castello

Publications and source records attributed to L Castello.

10 recordsLinked to original sources
PubMed2005

4-Hydroxynonenal signalling to apoptosis in isolated rat hepatocytes: the role of PKC-delta.

4-Hydroxynonenal, a significant aldehyde end product of membrane lipid peroxidation with numerous biochemical activities, has consistently been detected in various human diseases. Concentrations actually detectable in vivo (0.1-5 microM) have been shown to up-regulate different genes and modulate various enzyme activities. In connection with the latter aspect, we show here that, in isolated rat hepatocytes, 1 microM 4-hydroxynonenal selectively activates protein kinase C-delta, involved in apoptosis of many cell types; it also induces very early activation of Jun N-terminal kinase, in parallel increasing activator protein-1 DNA-binding activity in a time-dependent manner and triggering apoptosis after only 120 min treatment. These phenomena are likely protein kinase C-delta-dependent, being significantly reduced or annulled by cell co-treatment with rottlerin, a selective inhibitor of protein kinase C-delta. We suggest that 4-hydroxynonenal may induce apoptosis through activation of protein kinase C-delta and of Jun N-terminal kinase, and consequent up-regulation of activator protein-1 DNA binding.

Aldehydes↗
PubMed2005

Insulin sensitivity: gender-related differences in subjects with normal glucose tolerance.

BACKGROUND AND AIMS: To verify whether age and the perimenopausal state may herald the onset of the metabolic syndrome (MS) in females as compared to age-matched males, we studied subjects with normal glucose tolerance, according to ADA definition. METHODS AND RESULTS: In 368 eligible subjects subdivided into three age groups we measured insulin sensitivity by ISI-glycaemia, resistance by HOMA-IR, computed, during OGTT, from fasting and 2-h post-load plasma insulin and glucose concentrations. The significance of differences was tested between different age groups and between males and females within corresponding age groups. Insulin sensitivity fell slightly and insulin resistance rose significantly in the perimenopausal group as compared to younger and older female patients, and compared to men of the same age. This pattern remains after excluding patients with high blood pressure, and after adjusting for WHR and BMI by multivariate analysis. HOMA-IR averaged 2.9+/-1.8 in females, 2.2+/-1.2 in men aged 45-54 years (p<0.02), while in the other age groups insulin resistance was higher in men. CONCLUSION: The onset of MS during the menopause is associated with a physiological shift in insulin resistance occurring even in normal glucose tolerant subjects, suggesting that it may depend upon critical metabolic changes occurring specifically in that age period.

Adolescent↗
PubMed2005

Hyponatremia in liver cirrhosis: pathophysiological principles of management.

Hyponatremia is common in cirrhosis, where it impairs encephalopathy. It could be either due to excess water, or reduced Na, or a combination of both. The diagnosis can be established with clinical skills aided by simple data like weight, blood pressure and plasma electrolytes. The quantitative estimates of the water surfeit or solute deficit, easily performed with simple formulas and measurements, guide accurate and programmed treatment procedures, avoiding the occurrence of the ominous central pontine myelinolysis.

Body Water↗
PubMed2005

Pathways of glomerular toxicity of cyclosporine-A: an "in vitro" study.

BACKGROUND/AIMS: Knowledge of renal toxicity of cyclosporine-A (CyA) is clouded by multiple effects on different glomerular and tubular cells and on kidney and systemic hemodynamics. To focus on glomerular action of CyA we used glomeruli isolated in vitro, with the aim of dissecting the effects on recruitment of glomerular vasoconstricting systems, like endothelin-1 (ET) and angiotensins (AI and AII). METHODS: We studied the pathways of CyA damage on pig glomeruli isolated in vitro with the technique of sieving through mesh filters of different sizes, and incubated in an appropriate culture medium. The supernatant was sampled at different time intervals to measure ET, AI and AII concentrations upon addition of ET 10(-12) or CyA 4x10(-7)M, with or without either selective endothelin receptor A (ETA) or B (ETB), or unselective ETA-ETB receptor inhibitors. RESULTS: CyA increased ET concentration (from 9.7+/-0.3 to 11.4+/-0.4 pgxml-1, p<0.002), and the added ET released AI in the medium (from 26.6+/-4.7 to 39.1+/-4.6 pgxml-1, p<0.05) when ETB receptors were blocked. In contrast, CyA stimulated angiotensins release independent of ET receptors blockade, hence, irrespective of ET concentration in the medium, from 26.6+/-4.7 to 38.0+/-2.1 pgxml-1 for AI, p<0.05, and from 12.3+/-1.0 to 14.8+/-0.9 pgxml-1 for AII, p<0.05. CONCLUSION: CyA releases ET and angiotensins independently by a direct action. Glomerular CyA toxicity might be mediated by recruitment of vasoconstricting peptides and modulated by relative ETA and ETB receptor occupancy.

Angiotensin I↗
PubMed2004

Quantitative treatment of the hyponatremia of cirrhosis.

BACKGROUND: Hyponatremia represents a frequent complication of liver cirrhosis, associated with adverse events and death. It is caused either by excessive water retention or solute depletion, or a combination of both. AIMS: To determine the cause of hyponatremia clinically and to examine the usefulness of quantitative calculations of water excess and Na deficit to guide treatment. METHODS: We studied 23 patients with liver cirrhosis and PNa < or =131 meq/L to determine the cause of hyponatremia and results of quantitative treatment. RESULTS: The most frequent cause of hyponatremia was diuretic-induced Na depletion, which occurred in 14 out of 23 instances, while four patients had water excess. Hyponatremia was corrected after a quantitative estimate of the Na deficit or relative water excess by algebraic formulas. The former was quantitatively replenished as 3% NaCl, the latter was excreted with the technique of furosemide-induced diuresis and re-infusion of solute, but not water, losses. After quantitative replacement, there was a significant correlation (R=0.98, P< 0.001) between the Na concentration predicted mathematically and that actually measured. CONCLUSIONS: The hyponatremia of cirrhosis is frequently caused by diuretics. Its treatment can be effectively guided with the aid of quantitative estimates of Na deficit and/or water excess in all instances, although the methods of correction described are indicated in severe clinical conditions.

Aged↗
PubMed2000

Losartan, a selective inhibitor of subtype AT1 receptors for angiotensin II, inhibits neutrophil recruitment in the lung triggered by fMLP.

We have shown that losartan, a selective inhibitor of AT1 receptors for angiotensin II (AII), inhibits the binding of [3H]fMLP to neutrophil receptors (FPR). Here, we analyze, in Wistar rats, the effect of losartan on neutrophil recruitment in the lung triggered by fMLP. We found that i.v. infusion of losartan (0.4-20.0 microg/kg/min) inhibits neutrophil recruitment induced by i.t. instillation of fMLP, without affecting the responses induced by other stimuli, such as aggregated human IgG (aIgG), precipitating immune complexes (IC), or zymosan. Histological evaluation of lungs as well as the analysis of lung hemorrhage indices showed that losartan prevents tissue injury partially in fMLP-challenged rats. We also analyzed the effect of losartan on lung-neutrophil recruitment triggered by i.t. instillation of Pseudomonas aeruginosa. Not only was there a marked decrease in neutrophil recruitment but also a significant increase in the survival of rats instillated with Pseudomonas aeruginosa, as a consequence of losartan treatment. Our results support the notion that losartan may be useful in the treatment of certain lung inflammatory disorders associated with bacterial infectious diseases.

Angiotensin II↗
PubMed1997

Broth disk elution method for anaerobic bacteria: a collaborative study to assess its reliability for clinical purposes.

A collaborative study involving seven laboratories was undertaken to evaluate the reproducibility and the reliability of the broth disk elution test against anaerobic bacteria by comparing with the reference agar dilution method. A two breakpoint broth test was also evaluated. Assays were performed using the same testing conditions (i.e. medium, temperature, atmosphere and incubation time). One hundred Gram-negative and Gram-positive clinical isolates were initially studied. Overall agreement of 98.5% and 97.5%, were found for disk elution and the two breakpoint tests, respectively. In order to assess the reliability of the disk elution test, two different lots (LOT1 and LOT2) of disks of piperacillin and clindamycin were selected, to obtain two final concentrations after dilution (10 and 60 mg/mL; 1 and 4 mg/mL, respectively). Two hundred and eighty assays were performed against one strain of both Bacteroides fragilis(piperacillin MIC, 8.0 mg/mL; clindamycin MIC, <0.5 mg/mL) and Bacteroides thetaiotaomicron(piperacillin MIC, 16.0 mg/mL; clindamycin MIC, <0.5 mg/mL). With LOT 1, considering both species and both antibiotics, the agreement among six laboratories ranged from 85% to 100% (P > 0.05) with the higher concentration. Overall agreement among all laboratories was 91%. No optimal agreement (>90%) for clindamycin-Bacteroides thetaiotaomicron using the LOT1 (77%) was found. Since this finding was not observed with LOT2 (100% agreement), discrepancies were attributed to variation between lots. Overall agreement with LOT2 was 100% for all centres. The present study indicates that the broth disk elution method proved to be a reliable and suitable alternative for routine susceptibility testing for anaerobic bacteria, as a resistance screening method for clinical purposes.

Journal Article↗
PubMedDate not supplied

["In vitro" activity of ten antimicrobial agents against anaerobic bacteria. A collaborative study, 1999-2002].

The antimicrobial activity of ampicillin, ampicillin-sulbactam, cefoxitin, ceftriaxone, imipenem, piperacillin, piperacillin-tazobactam, clindamycin, metronidazole, and azitromycin was assesed against 166 strains of anaerobic bacteria recovered from eight hospitals in Buenos Aires. The strains studied were Bacteroides fragilis group (65), Fusobacterium spp. (26), Prevotella spp. (21), Porphyromonas spp. (10), Clostridium difficile (10), other clostridia (12), and gram-positive cocci (22). The MICs were determined by the agar dilution method according to NCCLS document M11-A5. Metronidazole and piperacillin-tazobactam were the most active antimicrobial agents tested and exhibited MIC90 values of < or = 2 microg/ml and < or = 4 microg/ml against gram-negative organisms, and < or = 2 microg/ml, and < or = 8 microg/ml against gram-positive organisms, respectively. Among beta-lactams the activity against gram-negative rods was in the following order: imipenem > piperacillin > cefoxitin > ceftriaxone > ampicillin. Among the gram-positive bacteria the decreased activity was: piperacillin > imipenem > cefoxitin > ceftriaxone > ampicillin. The majority of the species studied showed different degrees of resistance to clindamycin and azitromycin. Nevertheless, 90% of Fusobacterium nucleatum and Porphyromonas spp. isolates were inhibited by 0.125 mg/ml of clindamycin and azitromycin, respectively.

Anti-Bacterial Agents↗