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A Sola

Publications and source records attributed to A Sola.

At least 37 records · Page 2Linked to original sources
PubMed2003

Nucleotides modulate renal ischaemia-reperfusion injury by different effects on nitric oxide and superoxide.

1. The present study investigated the effects of kidney ischaemia duration on nitric oxide (NO) and superoxide (O2-) generation at reperfusion and the role of xanthine and adenosine as mediators of NO/O2- generation. 2. The effect of the duration of ischaemia on renal nucleotide levels was studied in two ischaemic groups (10 and 30 min). The role of adenosine and xanthine was studied in ischaemic-reperfused groups (subjected to 10 and 30 min ischaemia and 60 min reperfusion). 3. Tissue levels of adenosine decreased significantly after 30 min ischaemia, whereas xanthine/hypoxanthine levels increased concomitantly with renal dysfunction and histological damage. 4. Nitric oxide production increased significantly after 10 min ischaemia and 60 min reperfusion, whereas lipoperoxidation increased significantly after 30 min ischaemia and 60 min reperfusion. The administration of theophylline (40 mg/kg, i.p.) reversed the early increase in NO production. 5. Xanthine supplementation decreased renal function and increased lipoperoxidation. 6. In conclusion, NO/O2- production and the subsequent renal injury/dysfunction may be modified by changes in the adenosine and xanthine levels of the injured kidney, although the present data show a significant in vivo role only for xanthine.

Adenosine↗
PubMed2002

Taq I polymorphism of the vitamin D receptor and risk of severe diabetic retinopathy.

AIMS/HYPOTHESIS: Vitamin D, a molecule with antiproliferative, antiangiogenic, antioxidant and immunosuppressive effects, could play a role in the pathogenesis of severe diabetic retinopathy. We examined whether Taq I polymorphism of the vitamin D receptor is involved in the development of severe diabetic retinopathy. METHODS: 200 unrelated C-peptide-negative French Type I diabetic patients were randomly selected (male:female, 103:97, age 44.4 +/- 12.4 years, diabetes duration: 27.7 +/- 10.0 years, BMI: 24.3 +/- 3.4 kg/m(2), HbA(1c): 8.6 +/- 1.3 %). The Taq I site was analysed by PCR followed by digestion with Taq I enzyme. Diabetic retinopathy was assessed by retinal angiography and classified as presence (n = 101) or absence (n = 99) of severe (preproliferative or proliferative) diabetic retinopathy. RESULTS: Frequency of wild-type genotype TT was lower in patients with severe diabetic retinopathy (n = 27) when compared with control subjects (n = 42, OR = 0.5, p = 0.028). Allele frequencies were not different between patients (T: n = 112 and t: n = 90) and control subjects (T: n = 128, and t: n = 70, p = 0.075). Global chi(2) (df = 2): p = 0.064. In subjects with diabetes duration of more than 25 years, TT was lower in severe diabetic retinopathy (n = 14) than control subjects (n = 18, OR = 0.3, p = 0.01). Allele frequencies were different between patients (T: n = 68 and t: n = 66) and control subjects (T: n = 52, OR = 0.5, and t: n = 26, OR = 1.9, p = 0.034). Global chi(2) (df = 2): p = 0.024. In subjects with HbA(1c) over 9 %, Tt was higher in patients (n = 28) than control subjects (n = 15, OR = 3.1, p = 0.019). Allele frequencies were not different between patients (T: n = 52 and t: n = 38) and control subjects (T: n = 57, and t: n = 29, p = 0.31). Global chi(2) (df = 2): p = 0.035. CONCLUSION/INTERPRETATION: In French Type I (insulin-dependent) diabetic patients, we demonstrate an association between TT form (VDR) and low risk for severe diabetic retinopathy, especially in patients with long duration, and between Tt variant and high risk for severe diabetic retinopathy in subjects with poor glycaemic control.

Adult↗
PubMed2002

eNOS4 polymorphism of the endothelial nitric oxide synthase predicts risk for severe diabetic retinopathy.

BACKGROUND: Genetic factors may be involved in the development, and particularly in the severity, of diabetic retinopathy (DR), in addition to chronic hyperglycaemia. Increased nitric oxide generation has been suggested to play a significant role in the pathogenesis of DR. AIMS AND METHODS: To examine whether the eNOS4 is involved in the risk of severe DR, 200 unrelated Caucasian Type 1 diabetic patients of long duration were randomly selected (M/F 103/97, age 44.4 +/- 12.4 years, diabetes duration 27.7 +/- 10.0 years, body mass index 24.3 +/- 3.4 kg/m2, HbA1c 8.6 +/- 1.3%). The eNOS4 polymorphism was analysed by polymerase chain reaction, and DR by retinal angiography and classified as presence (n = 101) or absence (n = 99) of severe (proliferative or pre-proliferative) DR. RESULTS: The genotype distribution of eNOS4b/b (wild-type), eNOS4b/a (heterozygous) and eNOS4a/a (homozygous) was 72%, 24.5% and 3.5%, respectively. Frequency of eNOS4a/a was significantly lower in patients with severe DR (n = 0) when compared with controls (n = 7, odds ratio (OR) = 0 (95% confidence interval (CI) = 0.5-0.74), P = 0.02). eNOS4b/b was more frequent in patients with severe DR (n = 80) when compared with controls (n = 64, OR = 2.1 (95% CI = 1.1-4.12), P = 0.032). Frequency of eNOS4b/a was not different between the study (n = 21) and control groups (n = 28, ns). The allelic frequencies between the study and control groups were different (4b: n = 181 vs. n = 156, respectively, OR = 2.3 (95% CI = 1.27-4.25), P = 0.005; 4a: n = 21 vs. n = 42, respectively, OR = 0.4 (95% CI = 0.24-0.79), P = 0.005). CONCLUSIONS: We demonstrate in Caucasians with Type 1 diabetes that (i) eNOS4a/a is associated with absent or non-severe DR, and (ii) eNOS4b/b is associated with severe DR.

Adult↗
PubMed2001

Effects of adenosine on ischaemia-reperfusion injury associated with rat pancreas transplantation.

BACKGROUND: During cold preservation, cellular consumption of adenosine triphosphate leads to the accumulation of nucleotides and nucleosides. The precise role of adenosine in modulating the inflammatory response of cold-preserved pancreas after reperfusion remains to be elucidated. The aim of this study was to assess the influence of adenosine on the inflammatory response associated with the process of ischaemia-reperfusion in rat pancreas transplantation. METHODS: The effect of adenosine from preservation solution on the levels of high-energy nucleotides and their breakdown products after cold ischaemic preservation was determined. In addition, the inflammatory response associated with the process of ischaemia-reperfusion in pancreas transplantation was quantified with and without pretreatment with the adenosine antagonist theophylline, and during preservation of the organ in University of Wisconsin solution with and without adenosine. RESULTS: Adenosine from preservation solution is able to modify the nucleotide and nucleoside content of preserved pancreas, indicating that adenosine is incorporated and metabolized in tissue. Administration of the adenosine antagonist to transplanted rats moderated the increases in nitrite and nitrate, myeloperoxidase activity and lipoperoxidation levels in the pancreas. CONCLUSION: Adenosine in the preservation solution may enhance the inflammatory response in rat pancreas transplantation.

Adenosine↗
PubMed2001

Environmental factors and disturbances of brain development.

Foetal and neonatal brain is under the influence of environmental factors from maternal and extra-maternal origin. Based on the available data, these environmental factors can be classified into three arbitrary groups: (i) factors and maternal status with a demonstrated deleterious effect on the foetal brain (i.e. ethanol, cocaine, some drugs including anticonvulsants, some viral infections, maternal diabetes, untreated maternal phenylketonuria); (ii) factors highly suspected to interfere with foetal brain development (i.e. lead and other heavy metals, some drugs like benzodiazepines, nicotine); (iii) factors which have been shown to be safe for the developing brain in the available studies (i.e. low to moderate doses of caffeine, methadone). However, most of these studies do not address the potential risk of environmental factors on minimal to moderate cognitive and behavioural disturbances. Finally, the impact of the neonatal environment on brain development in very pre-term infants is probably underestimated.

Brain↗
PubMed2001

Protective effect of ischemic preconditioning on cold preservation and reperfusion injury associated with rat intestinal transplantation.

OBJECTIVE: To define the protective effect of ischemic preconditioning on cold ischemia and reperfusion injury associated with intestinal transplantation, and the role of nitric oxide in this process. SUMMARY BACKGROUND DATA: Ischemia/reperfusion injury continues to be a significant obstacle in small bowel transplantation. Preconditioning is a mechanism that protects against this injury. METHODS: To study the capacity of preconditioning to prevent cold ischemia-associated injury and the inflammatory response associated with intestinal transplantation, the authors studied a control group of animals, cold ischemia groups with or without previous preconditioning and with or without previous administration of L-NAME or NONOS, and intestinal transplantation groups with or without previous preconditioning and with or without previous administration of L-NAME or NONOS. RESULTS: Histologic findings and the release of lactate dehydrogenase into the preservation solution showed that preconditioning protects against cold ischemic preservation-associated injury. Preconditioning also prevented the inflammatory response associated with intestinal transplantation, measured by the above parameters and by neutrophil recruitment in the intestine. Inhibition of nitric oxide eliminates the protective effect. CONCLUSIONS: Preconditioning protects the intestinal grafts from cold preservation and reperfusion injury in the rat intestinal transplantation model. Nitric oxide is involved in this protection.

Animals↗
PubMed2001

CO2 in static mesenteric venous blood during intestinal ischemia and ischemic preconditioning in rats.

During intestinal ischemia, CO2 accumulates in tissue as a result of bicarbonate buffering of anaerobic acid generation. Previous studies have shown that nitric oxide (NO) generated during ischemic preconditioning acts as a glycolytic modulator, thus decreasing tissue lactate production. We studied if ischemic preconditioning induces NO-dependent changes in static mesenteric venous blood Pco2 values and CO2 accumulation during intestinal ischemia. Superior mesenteric venous (smv) acid base variables were studied in 4 groups of rats: a control group (C), an ischemic (90-min period of flow arrest) group (I), an ischemic group subjected to previous ischemic preconditioning (P), and an ischemic group subjected to previous ischemic preconditioning in which nitric oxide synthase (NOS) was inhibited by N-nitro-L-arginine methyl ester (L-NAME) administration (P+N). Preconditioning induced acidosis in smv blood during reperfusion before ischemia, but this effect was counteracted by L-NAME. Group P showed the lowest values of end-ischemic tissue lactate, smv blood CO2 accumulation, and LDH in perfusate, whereas group P+N showed the highest level of LDH in perfusate but the lowest end-ischemic smv blood Pco2 and acidity. We conclude that lower ischemic CO2 accumulation in static smv blood, but not lower end-ischemic Pco2, was related with the protective effect of ischemic preconditioning in our rat model. Thus, the use of stagnant smv blood Pco2 as an indicative of intestinal dysoxia can lead to misinterpretations if a broader acid-base picture is not considered.

Anaerobiosis↗
PubMed2001

Fructose-1,6-biphosphate in rat intestinal preconditioning: involvement of nitric oxide.

BACKGROUND AND AIMS: Inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by nitric oxide (NO) in intestinal preconditioning could modify the rate of formation of glycolytic intermediates. Fructose-1,6-biphosphate (F16BP) is a glycolytic intermediate that protects tissue from ischaemia/reperfusion injury. We evaluated if F16BP may be endogenously accumulated as a consequence of GAPDH inhibition by NO during intestinal preconditioning in rats. METHODS: We assessed: (1) effect of preconditioning on F16BP content; (2) effect of NO on GAPDH activity before and during sustained ischaemia; and (3) protective effect of F16BP in control, ischaemic, and preconditioned animals with or without administration of N-nitro-L-arginine methyl ester (L-NAME), NO donor, or F16BP. RESULTS: Preconditioned rats showed a significant transient decrease in GAPDH activity and also maintained basal F16BP levels longer than ischaemic rats. L-NAME administration to preconditioned rats reversed these effects. F16BP administration to ischaemic rats decreased protein release in the perfusate. Administration of F16BP to L-NAME treated rats attenuated the harmful effect of L-NAME. CONCLUSIONS: Our study indicates that F16BP may be endogenously accumulated in preconditioned rats as a consequence of inhibition of GAPDH by NO, and this may contribute to the protection observed in intestinal preconditioning.

Analysis of Variance↗
PubMed2000

Modification of oxidative stress in response to intestinal preconditioning.

Previous studies have demonstrated that intestinal preconditioning protects the organ from ischemia reperfusion damage. Xanthine oxidase mediating free radical generation contributes to the development of injury associated to ischemia reperfusion. Thus, any process able to modulate the oxygen free radical generation system could attenuate the injury. Also, it is known that nitric oxide is implicated in the preconditioning response. The aim of this work is to determine: (1) the effect of intestinal preconditioning on the xanthine oxidase system, (2) the relevance of this system in the development of injury, and (3) its relationship with nitric oxide. For this purpose, we have determined the activity of the xanthine dehydrogenase/xanthine oxidase system, the levels of its substrate (xanthine), and end-product (uric acid) and oxidant stress status in rat small intestine subjected to ischemic pre-conditioning. The effects of nitric oxide inhibition have also been evaluated. Results show that the percentage of xanthine dehydrogenase to xanthine oxidase conversion, xanthine, uric acid concentration, lipoperoxides, and reduced glutathione were significantly reduced in preconditioned rats irrespectively of nitric oxide inhibition. In summary, this work shows that oxidative stress in intestinal preconditioning is reduced as consequence of the diminished conversion of xanthine dehydrogenase to xanthine oxidase, and also as a consequence of the reduced availability of xanthine.

Animals↗
PubMed2000

Insufficient adaptation of hypoglycaemic threshold for cognitive impairment in tightly controlled type 1 diabetes.

UNLABELLED: It is well known that hypoglycaemic thresholds for hormones and symptoms occur at lower plasma glucose levels in patients with strict glycaemic control. However, whether the threshold for cognitive impairment also shifts is still an unresolved question. We studied 19 type 1 diabetic patients, including 8 with hypoglycaemia unawareness, aged 37.0 +/- 7.4 y.r., with diabetes duration 15.2 +/- 10.7 yr, and HbA1c 7.6 +/- 1.1%. Hypoglycaemic thresholds for hormones, symptoms, awareness and cognitive function using the 4-choice reaction time test (4RT), were measured every 30 min during a 150 min stepped 4.4 to 2.2 mM hypoglycaemic hyperinsulinemic clamp. We found that 4RT- accuracy deteriorated earlier than 4RT-time (3.2 and 2.7 mM, respectively, p<0.01), and that both correlated poorly with HbA1C before and after adjustment for age and diabetes duration (r=0.11, and 0.18, respectively). On the opposite, adrenaline, autonomic and neuroglycopenic symptoms, and awareness significantly correlated with HbA1c values (r=0.56, 0.70, 0.61, and 0.63, after adjustment, respectively). Furthermore, after allocating the patients into two subgroups according to HbA1c values (<8% n=12, and >=8% n=7), we found that, as opposed to other thresholds, accuracy and 4RT-time were minimally and not significantly influenced by glycaemic control, therefore exhibiting the smaller glucose thresholds shifts (- 0.2 and - 0.5 mM for accuracy and time, respectively, vs. 0.6 -0.8 for other thresholds). IN CONCLUSION: 1) the hypoglycaemic thresholds for cognitive dysfunction shift with strict glycaemic control, but not significantly and less than other thresholds, 2) as opposed to other reports, accuracy deteriorates earlier than speed during the 4RT test, and 3) these "maladapted" reactions may contribute to the higher risk for severe hypoglycaemia in subjects with tight glycaemic control.

Adult↗
PubMed1999

Modification of glyceraldehyde-3-phosphate dehydrogenase in response to nitric oxide in intestinal preconditioning.

BACKGROUND: Previous studies have demonstrated that intestinal preconditioning is triggered by an initial increase in nitric oxide synthesis. This confers resistance to the organ in face of a subsequently sustained period of ischemia-reperfusion. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key enzyme in the glycolytic cascade that could be modulated by nitric oxide. The purpose of the present study is to evaluate a possible inhibitory effect on intestinal GAPDH by the nitric oxide generated during preconditioning. This could lead to a reduction of lactate accumulation during subsequent ischemia. METHODS: GAPDH activity was measured after intestinal preconditioning, and the effect of nitric oxide synthase inhibition was evaluated. RESULTS: Preconditioning induced a significant, but transient, decrease in GAPDH activity. This effect appears to be correlated with a reduced amount of lactate accumulation during ischemia. Inhibition of nitric oxide synthesis reversed these changes. In addition, increased synthesis of nitric oxide was detected after preconditioning. CONCLUSIONS: In summary, this study indicates that nitric oxide generated during ischemic preconditioning could act as a glycolytic modulator during subsequent ischemia, through its effect on GAPDH activity.

Animals↗
PubMed1999

Direct coronal CT scanning of the neonatal chest.

BACKGROUND: The purpose of this study was to attempt to improve upon conventional coronal computed tomographic (CT) images of neonatal chest which to date have been made by reformatting thinly spaced axial images. MATERIALS AND METHODS: Nine neonates were studied by direct coronal CT scans with the patients' long axis 90 degrees to the scanning table. They were studied to further define their thoracic abnormalities detected on plain film. Spiral CT and cine scan (Imatron) were utilized. RESULTS: Congenital lung lesions such as congenital cystic adenomatoid malformation could not be diagnosed but their anatomical location could be accurately depicted, enabling easier surgical planning. The arterial supply to bronchopulmonary sequestrations was also identifiable. Tracheobronchial abnormalities such as tracheobronchus and bronchial atresia were also identifiable. Causing of air trapping, both intrinsic such as an atretic bronchus and extrinsic such as vascular compression were readily demonstrated. CONCLUSION: With neither special devices nor paraphernalia, the described method of direct coronal CT scans were both feasible and provided significant information. This technique allows for improved assessment of the tracheobronchial tree and more accurate detection, localization, and characteristics of lesions adjacent to the diaphragm.

Bronchi↗
PubMed1999

Toxicity of fructose-1,6-bisphosphate in developing normoxic rats.

Giving 500 mg/kg of fructose-1,6-bisphosphate intraperitoneally decreases hypoxic/ischaemic CNS injury of neonatal rats. Before administering fructose-1,6-bisphosphate to human neonates, its toxicity must be determined in neonatal animals. Thus, saline or 4,000, 6,000, or 8,000 mg/kg of fructose-1,6-bisphosphate was given intraperitoneally to normoxic 7 days old rats. One, 2, and 24 hr and 7 days later, blood Ca2+, PO(4)3-, blood urea nitrogen, and creatinine concentrations, and aspartate aminotransferase activity were measured. Organ pathology was determined at necropsy. Pups receiving 4,000 mg/kg of fructose-1,6-bisphosphate survived without evidence of injury or toxicity. All animals receiving 8,000 mg/kg and 27 percent of those receiving 6,000 mg/kg of fructose-1,6-bisphosphate died. Surviving fructose-1,6-bisphosphate-treated animals grew at the same rates and had similar weights as saline-treated animals. Nineteen percent of pups given 6,000 or 8,000 mg/kg of fructose-1,6-bisphosphate had mild perivascular fluid cuffing and/or microscopic pulmonary haemorrhage, but none of the animals given 4,000 mg/kg of the compound had evidence of injury. No other organ pathology was found in any of the animals. Renal and hepatic function were normal in all animals. Fructose-1,6-bisphosphate administration was associated with a significant increase in the fructose-1,6-bisphosphate concentration of blood. Administering 4,000 to 8,000 mg/kg of fructose-1,6-bisphosphate significantly decreased Ca2+ concentrations and increased PO(4)3- concentrations 1 and 2 hrs after fructose-1,6-bisphosphate administration. Similar changes in Ca2+ and PO(4)3- concentrations occurred after the administration of 10 mmol/kg of sodium phosphate. The wide margin of safety for fructose-1,6-bisphosphate (8 times the dose needed to prevent or reduce CNS injury) may render fructose-1,6-bisphosphate safe for use in neonates.

Animals↗
PubMed1998

Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems.

PURPOSE: We developed a scoring system for the assessment of perinatal asphyxia as depicted on MR images. METHODS: Four scoring systems were derived to evaluate MR images obtained in asphyxiated neonates: the basal ganglia (BG) score, the watershed (W) score, the combined basal ganglia/watershed (BG/W) score, and the sum of the BG and W scores, the summation (S) score. In addition, three MR sequences, T1-weighted, first-echo T2-weighted, and second-echo T2-weighted, were assessed for each patient for each scoring system. Neuromotor examinations were performed at ages 3 and 12 months, and cognitive development was tested at age 12 months. Statistical analysis was then performed to test the relationship between the MR scores and the outcome scores. RESULTS: The BG/W score, obtained with the first-echo T2-weighted sequence, was the most useful overall score for predicting neuromotor outcome at 3 and 12 months and cognitive outcome at 12 months. T1-weighted and first-echo T2-weighted sequences showed a stronger association with outcome in patients imaged during the first postnatal week, whereas second-echo T2-weighted sequences showed a stronger association with outcome in patients imaged during the second postnatal week. CONCLUSION: It appears that, with the use of the BG/W score, MR imaging discriminates accurately between patients with good and poor neuromotor and cognitive outcome at 3 and 12 months. In terms of our scoring systems, the first-echo T2-weighted sequence appears to discriminate best between patients with good and poor 3- and 12-month outcomes. Proper use of the imaging sequences and scoring systems described in this article can increase the knowledge base upon which treatment decisions are made in asphyxiated neonates.

Asphyxia Neonatorum↗