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Biomedical subjects

G del Rio

Publications and source records attributed to G del Rio.

11 recordsLinked to original sources
PubMed2002

cDNA microarray analysis of changes in gene expression induced by neuronal hypoxia in vitro.

We used cDNA microarray gene expression profiling to characterize the transcriptional response to exposure of cultured mouse cerebral cortical neurons to hypoxia for 24 hr. Of 11,200 genes examined, 1,405 (12.5%) were induced or repressed at least 1.5-fold, whereas 26 known genes were induced and 20 known genes were repressed at least 2.5-fold. The most strongly induced genes included genes coding for endoplasmic reticulum proteins (Ero1L/Giig11, Sac1p, Ddit3/Gadd153), proteins involved in ubiquitination (Arih2, P4hb), proteins induced by hypoxia in non-neuronal systems (Gpi1, Aldo1, Anxa2, Hig1), and proteins that might promote cell death (Gas5, Egr1, Ndr1, Vdac2). These findings reinforce the importance of endoplasmic reticulum-based mechanisms and of protein-ubiquitination pathways in the neuronal response to hypoxia.

Animals↗
PubMed2001

Mining DNA microarray data using a novel approach based on graph theory.

The recent demonstration that biochemical pathways from diverse organisms are arranged in scale-free, rather than random, systems [Jeong et al., Nature 407 (2000) 651-654], emphasizes the importance of developing methods for the identification of biochemical nexuses--the nodes within biochemical pathways that serve as the major input/output hubs, and therefore represent potentially important targets for modulation. Here we describe a bioinformatics approach that identifies candidate nexuses for biochemical pathways without requiring functional gene annotation; we also provide proof-of-principle experiments to support this technique. This approach, called Nexxus, may lead to the identification of new signal transduction pathways and targets for drug design.

Apoptosis↗
PubMed2001

Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation.

The endoplasmic reticulum (ER) is the site of assembly of polypeptide chains destined for secretion or routing into various subcellular compartments. It also regulates cellular responses to stress and intracellular Ca(2+) levels. A variety of toxic insults can result in ER stress that ultimately leads to apoptosis. Apoptosis is initiated by the activation of members of the caspase family and serves as a central mechanism in the cell death process. The present study was carried out to determine the role of caspases in triggering ER stress-induced cell death. Treatment of cells with ER stress inducers such as brefeldin-A or thapsigargin induces the expression of caspase-12 protein and also leads to translocation of cytosolic caspase-7 to the ER surface. Caspase-12, like most other members of the caspase family, requires cleavage of the prodomain to activate its proapoptotic form. Caspase-7 associates with caspase-12 and cleaves the prodomain to generate active caspase-12, resulting in increased cell death. We propose that any cellular insult that causes prolonged ER stress may induce apoptosis through caspase-7-mediated caspase-12 activation. The data underscore the involvement of ER and caspases associated with it in the ER stress-induced apoptotic process.

Animals↗
PubMed2001

APAP, a sequence-pattern recognition approach identifies substance P as a potential apoptotic peptide.

We have previously described a novel cancer chemotherapeutic approach based on the induction of apoptosis in targeted cells by homing pro-apoptotic peptides. In order to improve this approach we developed a computational method (approach for detecting potential apoptotic peptides, APAP) to detect short PAPs, based on the prediction of the helical content of peptides, the hydrophobic moment, and the isoelectric point. PAPs are toxic against bacteria and mitochondria, but not against mammalian cells when applied extracellularly. Among other peptides, substance P was identified as a PAP and subsequently demonstrated to be a pro-apoptotic peptide experimentally. APAP thus provides a method to detect and ultimately improve pro-apoptotic peptides for chemotherapy.

Amino Acid Sequence↗
PubMed1993

Antimicrobial prophylaxis in urologic surgery: does it give some benefit?

Three types of antibiotic prophylactic regimens were evaluated versus a control without prophylaxis (group A: 3,912 cases) in urologic surgery. The antibiotic regimens were: group B = cefazolin 1 g/12 h/3 days (3,660 cases); group C = cefonicid 1 g/24 h/3 days (2,076 cases), and group D = cefonicid 1 g single dose (3,169 cases). The parameters used were the comparison of the corresponding rates of postsurgical sepsis and operative wound infections. Numeric investigations for the validity of a retrospective study (unpaired data) were performed: homogenicity test, relative risk point estimate and confidence limits (95%), and etiological fraction point estimate and confidence limits (95%). Chi-square for other purposes were performed. Endoscopic handling was considered homogeneous (same infective risk), while open surgery was heterogeneous (p < 0.001). In order to avoid probable bias, a correction factor was used. Although in different degrees, prophylaxis significantly reduced the morbidity of surgical wound infections (p < 0.001; etiological fraction > 90%). The differences (p < 0.01) between groups B and C/D were attributed to pharmacokinetic causes (short T 1/2 of cefazolin). To obtain the maximum protective effect, the use of antibiotics with a T 1/2 of > 4 h is suggested. There was no resistant mutans in previously sensitive strains. However, a significant selection of intrinsically resistant strains was observed. Monodose offers at lest the same advantages as multiple-dose therapy. In addition, the monodose selected in a lesser proportion both the resistant strains (p < 0.001) and the number of microbial associations (p < 0.01).

Cefazolin↗
PubMed1991

Effect of 6-month gliclazide treatment on insulin release and sensitivity to endogenous insulin in NIDDM: role of initial continuous subcutaneous insulin infusion-induced normoglycemia.

In 10 obese, new-onset non-insulin-dependent diabetes mellitus (NIDDM) patients (group A), continuous subcutaneous insulin infusion (CSII) was used to induce normoglycemia during 14 days. Fasting blood glucose was 4.6 +/- 0.2 mmol/L and mean daily blood glucose 5.8 +/- 0.2 mmol/L at the end of the CSII period. This excellent glycemic control was obtained with 35 +/- 4.8 U of insulin per day, corresponding to 0.47 +/- 0.06 U/kg/24 hours. Endogenous insulin production was markedly suppressed, since urinary C-peptide was reduced from 18.5 +/- 0.12 to 7.9 +/- 0.25 nmol/24 hours. Gliclazide was given to group A following CSII, and to five obese NIDDM patients (group B) in their habitual hyperglycemic state. Gliclazide maintained in group A, and induced in group B, excellent metabolic control. This was accompanied by the appearance of a small first-phase insulin response to intravenous glucose, and significant increases in the mean-daily-insulin to mean-daily-blood-glucose ratio, as well as in the 24-hour urinary C-peptide-to-glucose ratio. The gliclazide effects tended to be more pronounced in group A. No significant effect was seen on efficacy of endogenous insulin (slope of disappearance of blood glucose divided by insulin levels). During 6 months of gliclazide treatment, excellent glycemic control was maintained in all patients. This was paralleled by unchanged stimulation by gliclazide of first-phase insulin response to glucose, and augmented mean 48-hour insulin-to-glucose and urinary C-peptide-to-glucose ratios. No change in the ratio of glucose disposal to endogenous insulin was noted. We conclude that physiologic insulin replacement may induce normoglycemia in NIDDM, indicating that insulin resistance is not of clinical significance; gliclazide has a beta-cell-stimulating action that is maintained quantitatively unchanged for at least 6 months; the therapeutic effect of gliclazide in NIDDM seems to be mainly, if not exclusively, the result of its beta-cytotrophic action. Initial normoglycemia, induced here by CSII, may have a lasting enhancing effect on the gliclazide action.

Blood Glucose↗
PubMed1991

Effect of 6 months' gliclazide treatment on insulin release and sensitivity to endogenous insulin in NIDDM: role of initial CSII-induced normoglycemia.

In 10 obese, newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients (group A) continuous subcutaneous insulin infusion (CSII) was used to induce normoglycemia over a period of 14 days. Fasting blood glucose was 4.61 +/- 0.22 mmol/l and mean daily blood glucose 5.83 +/- 0.27 mmol/l at the end of the CSII period. This excellent glycemic control was obtained with 35 +/- 4.8 U insulin per day, corresponding to 0.47 +/- 0.06 U/kg/24 h. Endogenous insulin production was markedly suppressed, since urinary C-peptide was reduced from 56 +/- 0.35 to 24 +/- 0.76 micrograms/24 h. Thus, physiological insulin replacement induced normoglycemia in NIDDM, indicating that insulin resistance is not clinically important. Gliclazide was given to group A following CSII and to 5 obese NIDDM patients (group B) in their habitual hyperglycemic state. Gliclazide maintained in group A and induced in group B excellent metabolic control. This was accompanied by the appearance of a small first-phase insulin response to iv glucose and by significant increases in the mean daily insulin to mean daily blood glucose ratio and in the 24-h urinary C-peptide to glucose ratio. The gliclazide effects tended to be more pronounced in group A. No significant effect was seen on sensitivity to endogenous insulin (slope of disappearance of blood glucose as function of insulin response to glucose infusion). During the 6 months of gliclazide treatment, excellent glycemic control was obtained in all patients. This was paralleled by unchanged stimulation by gliclazide of first-phase insulin response to glucose as well as mean by 48-h insulin to glucose and urinary C-peptide to glucose ratios. Again, sensitivity to endogenous insulin was not augmented. We conclude that gliclazide has a beta-cell-stimulating action which is maintained quantitatively unchanged for at least 6 months. The therapeutic effect of gliclazide in NIDDM seems to be mainly, if not exclusively, the result of its beta-cytotrophic action. Initial normoglycemia, induced here by CSII, may have a lasting enhancing effect on gliclazide action.

Blood Glucose↗
PubMed1989

Ticarcillin/clavulanate in severe infections in patients with varying renal function.

The therapeutic efficacy of ticarcillin/clavulanate was assessed in 71 patients with severe infections: 38 acute pyelonephritis, 16 septicaemia and 19 miscellaneous infections. The patients were classified according to their renal function in: Group A, normal (16 cases); B, mild renal impairment (RI) with creatinine clearance (Clcr) between 80 and 40 ml/min (18 cases); C, moderate RI with Clcr between 40 and 15 ml/min (12 cases); D, severe RI with (Clcr) between 15 and 5 ml/min (13 cases) and E, terminal with (Clcr) less than 5 ml/min (12 cases). A total of 105 microorganisms (48.6% resistant to ticarcillin): 31 Pseudomonas aeruginosa, 18 Escherichia coli, 21 other Enterobacteriaceae, 2 Haemophilus influenzae, 10 Bacteroides spp., 14 enterococci, 8 staphylococci and 1 streptococcus, were isolated. All except six Ps. aeruginosa were sensitive to ticarcillin/clavulanate, using 75:10 microgram discs. Bacteriological eradication was obtained in 97% of the cases on the third day and at the end of treatment, and in 82% of the cases after one month. In all the assessable cases, the clinical symptoms disappeared on the third day except in one patient who developed a resistant strain (Klebsiella oxytoca). The wide range of bacteria assessed and the clinical-bacteriological success rates demonstrated that the ticarcillin/clavulanate combination had an efficacy/safety profile that could be considered excellent. Tolerance was good and side effects were not observed. This study confirms the practical efficacy of the recommended dosages derived from our previous kinetic studies in RI.

Adult↗
PubMed1986

Pharmacokinetics of the combination of ticarcillin with clavulanic acid in renal insufficiency.

The pharmacokinetics of ticarcillin and clavulanic acid were studied by blood and urine assay methods in 25 patients divided into five groups with varying degrees of renal insufficiency i.e. mild, moderate and severe renal insufficiency, almost anuric patients and those requiring haemodialysis (groups A to E). A single dose of 5.2 g Timentin (5.0 g ticarcillin and 200 mg clavulanic acid) was administered intravenously by infusion over 30 min. The average elimination half-life (T1/2) of ticarcillin increased from 0.95 h in patients with creatinine clearance (Clcr) of 80 ml/min to 1.8, 4.4, 6.9 and 11.2 h respectively in mild, moderate and severe renal insufficiency and in almost anuric patients. The T1/2 values for clavulanic acid were 0.75, 0.9, 2.0, 2.5 and 4.8 h in the same groups. The area under concentration-time curve (AUC) for ticarcillin increased from 787 to 2839 mg/l/h and for clavulanic acid from 12.8 to 29 mg/l/h when group mean values from patients with mild and severe renal insufficiency were compared. The plasma clearance (Clpl) of clavulanic acid was in all groups greater than that of ticarcillin i.e. 166 and 100 ml/min vs. 79.2 and 25.0 ml/min when comparing mean values from groups with mild and severe renal insufficiency respectively. The plasma clearance ratio clavulanic acid/ticarcillin increased proportionally to the degree of renal insufficiency from a value of 1.5 in normal subjects to between 3.3 and 3.8 in more advanced cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1983

[Isolated hematurias: histologic and immunologic study].

An immunologic study and a renal biopsy were performed in 64 patients with isolated hematuria. Fifty of them had macroscopic hematuria and 14 microscopic hematuria. The kidney was normal in 66% by light microscopy; in the remaining 34% glomerular lesions were moderate: thickening of the mesangial matrix, diffuse or segmentary mesangial proliferation. Four patterns were observed by immunofluorescence: C3 located either in the mesangium, or at the level of the vascular pole, mesangial IgA, mesangial IgM and lack of deposits. According to our experience IgA nephropathy presenting as isolated hematuria has a better prognosis than the other symptomatic forms of this glomerulonephritis. No patient with the other renal pathological changes so far developed hypertension or renal failure. We prefer to perform biopsies on patients with isolated hematuria, considering the frequency of IgA nephropathy and the possibility of finding mesangial deposits of IgM and C3 whose significance is so far poorly known.

Adolescent↗