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S Blot

Publications and source records attributed to S Blot.

27 records · Page 2Linked to original sources
PubMed1996

Improved survival in rats administered NG-nitro L-arginine methyl ester due to converting enzyme inhibition.

Blockade of the renin-angiotensin system (RAS) prevents the increase in blood pressure (BP) induced by chronic administration of NG-nitro L-arginine methyl ester (L-NAME) in rats. In the present study, we showed how a converting enzyme inhibitor can prevent the end-stage tissue damage due to chronic nitric oxide (NO) synthase blockade and thus improve the survival rate. Three experiments were performed. In the first, rats (n = 10) were given L-NAME (50 mg/kg) and 10 other rats were given L-NAME plus quinapril (10 mg/kg) starting 1 month after L-NAME administration. Ten untreated rats were used as controls. Rats were killed after 2 months, and the RAS, renal function, and renal morphology were analyzed. In the second experiment, a similar protocol was used, and function and morphological damage in renal slices and cervical medullary tissue were assessed after 4 months of L-NAME and 3 months of quinapril + L-NAME. In the third experiment, a similar protocol was used, but to establish survival curves, the animals were not killed. L-NAME significantly increased BP without causing any significnat changes in plasma renin activity (PRA) at 2 months. The aortic wall cyclic GMP content was significantly decreased, and the angiotensin-converting enzyme (ACE) activity was increased by L-NAME. Quinapril significantly reversed the high BP induced by L-NAME without changing the decrease in the aortic wall cyclic GMP. Two-month L-NAME treatment decreased renal function and damaged renal tissue. Quinapril prevented both proteinuria and morphological damage. Four-month L-NAME treatment induced renal end-stage damage and infarctions of the cervical medulla. Quinapril prevented this end-stage damage in the kidney and cervical medulla. Quinapril therefore prevented the increased mortality due to L-NAME. Hence, inhibition of ACE, despite its lack of effect on arterial wall cyclic GMP, does reverse the hypertension and prevent end-stage vascular damage induced by chronic L-NAME in target organs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Synaptic transmission blockade increases plasminogen activator activity in mouse skeletal muscle poisoned with botulinum toxin type A.

Experimental denervation, either by nerve crush or axotomy, leads to a dramatic increase in muscle plasminogen activator (PA) activity, suggesting a regulation of muscle PA levels by some neural influence (Festoff et al., 1986, J. Cell Biol., 103:1415-1421; Hantaï et al., 1990, Proc. Natl. Acad. Sci. U.S.A., 87:2926-2930). The Botulinum toxin (BoTx) type A is known to selectively interrupt the release of acetylcholine without structurally altering synaptic morphology. In the present study we have used acute BoTx poisoning of hind limb muscles to further explore the neural regulation of muscle PA activities directly after poisoning and during the process of collateral reinnervation. Electromyographic recording and study of ultraterminal sprouting after zinc iodideosmium and silver-cholinesterase staining were used to monitor "denervation" and reinnervation. Muscle choline acetyltransferase activity did not decrease, as is observed after experimental denervation, but in contrast increased and, therefore, reflected the functional integrity of intramuscular nerve endings. Within 2 days of BoTx poisoning, muscle urokinase-PA, and to a lesser extent, tissue-PA activities, rose in muscle extracts as shown by an amidolytic assay and fibrin zymography. When reinnervation occurred, muscle urokinase-PA activity decreased but did not return to baseline levels within the 80 days of our study. These results suggest that cholinergic transmission-regulated events determine activity of muscle PAs and that PAs likely have a role in neuromuscular formation and plasticity.

Amino Acid Sequence↗
PubMed1995

The mouse mutation muscle deficient (mdf) is characterized by a progressive motoneuron disease.

Muscle deficient (mdf) is an autosomal-recessive mutation mapped to mouse chromosome 19. The clinical phenotype and the muscle histopathology, briefly described in 1980, and the nervous system histopathology are detailed in the present study. Homozygotes develop a posterior waddle at 4 to 8 weeks of age. Soon thereafter, the hindlimbs become paralyzed and weakness appears in forelimbs, leading to a serious disability. The disease progresses slowly and the mean lifespan is reduced to 8 months. Skeletal muscles exhibit a neurogenic atrophy with signs of reinnervation. Peripheral nerves display axonal degeneration. Neurons within the spinal cord ventral horn, and some motor nuclei of the brain stem, are affected by a cytoplasmic vacuolar degeneration. Ascending and descending spinal cord tracts appear normal. An astrogliosis, restricted to the ventral horn of the spinal cord, occurs in mdf/mdf mice of 10 weeks of age. These clinical and histological features are indicative of a progressive motor neuronopathy. Among the murine spinal muscular atrophies, the programmed cell death of the mdf motoneurons is morphologically similar to wobbler. Because of the long time course, the mdf mutation may represent a valuable tool for understanding juvenile motoneuron diseases with chronic evolution, even though the murine locus is not syntenic with the human ones.

Animals↗
PubMed1994

Spinal cord infarcts during long-term inhibition of nitric oxide synthase in rats.

BACKGROUND AND PURPOSE: Chronic hypertension is a major predisposing factor for stroke in humans. It has recently been shown that long-term inhibition of nitric oxide synthase activity causes a gradual time-dependent increase in arterial blood pressure in rats. We used this new animal model of chronic hypertension to study the occurrence and spatial features of infarcts in the central nervous system. METHODS: Rats were treated with a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, dissolved in the drinking water at 50 mg/kg per day for 11 weeks. The brains and spinal cords of hypertensive rats with and without motion disturbances were processed for standard microscopic examination. RESULTS: Seventy-nine percent of the hypertensive rats showed motion dysfunctions, especially front leg paralysis, and/or died suddenly when their systolic blood pressure reached approximately 215 mm Hg after approximately 7 weeks of treatment. All of the hypertensive rats with stroke had spinal cord infarcts (90% at the cervical or cervicothoracic level) either alone or combined with brain lesions (30%). These structural alterations ranged from focal areas of pale, spongy tissue to large necrotic sites with vascular alterations, including thickened or fibrinoid degenerated vessel wall, macrophage invasion, and reactive astrocytes. CONCLUSIONS: Infarcts occurred in the central nervous system with a high incidence in the spinal cord of hypertensive rats in which nitric oxide synthase was chronically blocked. This location of the hypertensive neuropathologic sequelae contrasts with the model of stroke-prone spontaneously hypertensive rats. The results suggest that nitric oxide is a key factor in spinal cord arteriolar vasomotion and structure in rats.

Amino Acid Oxidoreductases↗
PubMedDate not supplied

Prevalence and risk factors for colonisation with gram-negative bacteria in an intensive care unit.

OBJECTIVE: To investigate prevalence and determine risk factors for colonisation with Gram-negative bacteria in ICU patients. DESIGN: Prospective, surveillance study. SETTING: 26-bed surgical and paediatric ICU. PATIENTS: 159 patients--whereof 22 infants--admitted to the surgical/paediatric ICU over a two-month period. INTERVENTION: In all patients routine microbiological monitoring was performed by thrice weekly oral swabs, urine sampling and, additionally, tracheal aspirates in patients on mechanical ventilation (MV) and by anal swabs once weekly. RESULTS: Population characteristics: Mean age of the adult population was 51.1 +/- 17.6 year. Mean age of the paediatric population was 6.3 +/- 5.3 year. The mean APACHE II-score was 18 +/- 9.1. The mean PRISM-score was 9.7 +/- 5.4. The mean ICU stay was 7.5 +/- 11.4 days. 43.4 percent of patients received mechanical ventilation (MV). The mean number of mechanical ventilation days was 11.1 +/- 14.7 days. 32.1% of patients experienced colonisation with Gram-negative bacteria. Prevalence of colonisation increased with length of ICU stay. The probability of colonisation was 24% after an ICU stay of 3 days (= median ICU stay). Time to colonisation was not different between the controlled sites (p > 0.05). 47% of colonizations were due to multiresistant strains. Higher APACHE II-scores and MV were associated with a higher prevalence of colonisation (p < 0.01). The ICU mortality was 8% among adult and 4% among paediatric patients. CONCLUSION: Patients with high APACHE II-scores, on mechanical ventilation and with an ICU stay of more than 3 days are most at risk for colonisation with Gram-negative bacteria. These patients should be cared with the optimal precautions in the prevention of colonisation and infection.

APACHE↗
PubMedDate not supplied

Invasive aspergillosis in critically ill patients: analysis of risk factors for acquisition and mortality.

OBJECTIVE: To investigate outcome in patients who develop invasive aspergillosis in the ICU, and to evaluate whether specific risk factors for the acquisition of invasive aspergillosis are associated with mortality. DESIGN: Retrospective cohort study (07/1997-12/1999) with screening of 8988 admissions. SETTING: 54-bed ICU of the 1060-bed Ghent University Hospital. PATIENTS: 38 ICU patients with invasive aspergillosis. Invasive aspergillosis was defined as proven by positive histology and tissue culture and as probable by a combination of clinical suspicion as well as microbiological and radiological data. Seventeen patients had risk factors (neutropenia, haematological malignancy, immunosuppressive therapy). In the other 21 apparently immunocompetent patients, invasive aspergillosis was a complication following ARDS, COPD, pneumonia, acute liver failure, burns, severe bacterial infection and malnutrition. MEASUREMENTS: Population characteristics and outcome were compared for patients with and without risk factors for the acquisition of invasive aspergillosis. RESULTS: Patients with risk factors had higher APACHE II scores. No difference was found between patients with and without risk factors in in-hospital mortality (82% vs. 71%; p=0.431). In patients with specific risk factors, the observed mortality was not different from the mortality as expected on basis of the APACHE II (p=0.940). In patients without risk factors the observed mortality exceeded the expected mortality (p<0.001). CONCLUSION: The incidence of invasive aspergillosis in this series is 4/1000 admissions. No difference in mortality was found between patients with and without risk factors for the acquisition of invasive aspergillosis. Yet, the prognosis of the patients without risk factors seems to alter more seriously by the development of this infection.

APACHE↗
PubMedDate not supplied

Ventilator-associated pneumonia in a tertiary care ICU: analysis of risk factors for acquisition and mortality.

OBJECTIVE: To investigate the incidence, risk factors and mortality of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients. DESIGN: Prospective, observational, population-based study. SETTING: The medical (14-bed) and surgical ICU (26-bed) of the Ghent University Hospital. METHODS: All 1295 patients admitted to the ICU during 4 three-month periods between 1996 and 1998 were included. A set of demographic and clinical variables were collected at the day of admission and during the ICU course. RESULTS: The incidence of VAP among ICU patients ventilated at least 48 hours was 23.1%. The mean time to the development of VAP was 9.6 days with a median of 6 days. In the population of patients ventilated for at least 48 hours, a comparison was made between patients with (n = 89) and without VAP (n = 296). Patients with VAP had a significant longer ICU stay, with a longer ventilation dependency. Logistic regression analysis identified admission diagnosis other than trauma (OR: 0.51, 95% CI: 0.29-0.89; p = 0.02) and the length of ICU stay (OR: 1.05, 95% CI: 1.03-1.07; p < 0.001) to be independently associated with the acquisiton of VAP. In comparison with the total study population, patients with VAP had a higher ICU mortality (20.2% vs. 12.0%; p = 0.04), but not in the cohort group of patients at risk for VAP (ventilated > 48 hours)(20.2% vs. 31.3%; p = 0.03). The factors independently associated with death were higher SAPS II scores (OR 1.02, 95% CI: 1.003-1.032; p = 0.02), an admission diagnosis other than trauma (OR 0.36, 95% CI: 0.17-0.75; p = 0.006) and length of ICU stay (OR 0.97, 95% CI: 0.946-0.995; p = 0.02). This model did not recognize VAP as an independent predictor of death (OR 0.79, 95% CI: 0.41-1.53; p = 0.492). CONCLUSIONS: The incidence of VAP in our ICU is 23.1%. Length of ICU stay and an admission diagnosis other than trauma are major risk factors for the development of this nosocomial infection. VAP is associated with a high fatality rate. However, after adjustment for disease severity and length of ICU stay, VAP was not identified as an independent predictor of death.

Adult↗