Biological effects of sarafotoxin in rat liver.
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Animals↗
Biomedical subjects
C Garcia
Publications and source records attributed to C Garcia.
MELAS: clinical features, biochemistry, and molecular genetics.
We studied 23 patients with clinically defined mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), 25 oligosymptomatic or asymptomatic maternal relatives, and 50 mitochondrial disease control subjects for the presence of a previously reported heteroplasmic point mutation at nt 3,243 in the transfer RNA(Leu(UUR)) gene of mitochondrial DNA. We found a high concordance between clinical diagnosis of MELAS and transfer RNA(Leu(UUR)) mutation, which was present in 21 of the 23 patients with MELAS, all 11 oligosymptomatic and 12 of 14 asymptomatic relatives, but in only five of 50 patients without MELAS. The proportion of mutant genomes in muscle ranged from 56 to 95% and was significantly higher in the patients with MELAS than in their oligosymptomatic or asymptomatic relatives. In subjects in whom both muscle and blood were studied, the percentage of mutations was significantly lower in blood and was not detected in three of 12 asymptomatic relatives. The activities of complexes I + III, II + III, and IV were decreased in muscle biopsies harboring the mutation, but there was no clear correlation between percentage of mutant mitochondrial DNAs and severity of the biochemical defect.
Acidosis, Lactic↗
Paediatric dialysis and renal transplantation in the state of Rio Grande do Sul, Brazil.
Renal replacement therapy (RRT) for Brazilian children with uraemia has been utilized since 1970 in the state of Rio Grande do Sul. One hundred and eighty patients receiving this therapy between 1970 and 1988 have been reviewed. The annual acceptance rate of new paediatric patients in this period increased from 0.6 to 6.5 patients per million child population. Glomerulonephritis (36.1%) and pyelonephritis including urological anomalies (31.7%) were the most frequent causes of end-stage renal disease. Outpatient hospital haemodialysis was the primary form of dialytic treatment in patients 5-15 years of age. Continuous ambulatory peritoneal dialysis was more often used in patients less than 5 years of age. The survival after 1 year on dialysis was 79.9% for children aged 5-15 years starting dialysis during the period 1985-1988. Fluid overload with congestive heart failure and infection were the main causes of death in children on dialysis. Eighty-four children received 93 grafts; only 14 (15%) were from cadaveric donors. One-year patient and graft survival of first living-related donor transplants were 92.2% and 78.5% respectively during the period 1985-1988. Infection accounted for 43.5% of deaths after transplantation. We conclude that RRT is becoming increasingly successful for children in our region but that greater emphasis upon patient compliance with all forms of RRT and upon cadaver kidney donation is needed.
Adolescent↗
Changing perspective on gastrointestinal complications in patients undergoing cardiac surgery.
There has been a documented shift towards increasing age and severity of illness in the patient population undergoing cardiac surgery. To determine if there was a coincident change in frequency, gastrointestinal (GI) complications were prospectively recorded in a consecutive series of 5,438 patients undergoing cardiac surgery from 1983 to 1991. There were 73 complications in 69 patients (incidence = 1.4%) defined as any GI condition that required transfer to an acute care unit, surgical intervention, blood transfusion, or treatment that prolonged the hospital course. Fourteen patients died, a mortality rate of 20% for patients with GI complications (p less than 0.001 versus patients without GI complications). The most frequent complications were those of gastric ulceration despite routine use of H2-receptor blocking agents. Thirty-six patients had upper GI (UGI) bleeding from gastric ulceration with 4 patients requiring operative intervention to control hemorrhage and 6 fatalities in patients with UGI bleeding. Two additional patients died of septic complications following gastroduodenal perforation or penetration. Six patients experienced bowel obstruction or prolonged bowel dysfunction (three Ogilvie's syndrome) with two requiring laparotomy. There were four cases of cholecystitis, two cases of pancreatitis, and the remaining cases were equally divided among common septic complications (diverticulitis and ischemic injury among others). Three patients with massive intestinal infarction died. GI complications were significantly associated with older patients (p less than 0.01) and valve surgery (p = 0.002) but were not more common in women. When considered as a separate group, patients with acid-peptic complications had longer perfusion times, increased use of vasopressors, and more frequent utilization of the intra-aortic balloon pump. In contrast to prior studies, this investigation indicates that GI complications associated with acid-peptic erosion of the UGI tract tend to occur in a different patient group than those with other GI complications. Older patients and/or those with a prior history of peptic ulcer symptoms, as well as those who experience prolonged perfusion times, low cardiac output, or prolonged ventilatory support, should be under rigorous gastric pH surveillance and receive aggressive prophylactic treatment with high-dose H2 antagonists, antacids, and/or sucralfate.
Aged↗
Influence of long-term hypoxia on tyrosine hydroxylase in the rat carotid body and adrenal gland.
Tyrosine hydroxylase (TH) protein was measured in the carotid body and adrenal gland of rats exposed to normobaric hypoxia (10% O2 in nitrogen) for 3, 7, 14 or 22 days. After 22 days of hypoxia, a gradual increase in TH protein content was observed in the carotid body and in the adrenal gland, reaching 168% and 148% of the normoxic controls, respectively. To determine if the increase in TH protein content in the carotid body could alter catecholamine biosynthesis, in vitro TH activity and catecholamine turnover were measured in rats submitted to hypoxia for 14 days. TH activity was increased by 11.2-fold, while the turnover of dopamine and norepinephrine was increased by 14.8- and 5.4-fold, respectively. The data show that long-term hypoxia exerts a stimulatory influence on TH protein in the carotid body and adrenal gland in addition to an elevation in dopamine and norepinephrine biosynthesis in the carotid body.
Adrenal Glands↗
A one-minute oxidase test to detect Vibrio strains isolated from cultures on thiosulphate-citrate-bile salts-sucrose (TCBS) medium.
Vibrio cholerae is oxidase positive, a primary characteristic used to differentiate it from Enterobacteriaceae. But false negative oxidase test results have been obtained with colonies from thiosulphate-citrate-bile salts-sucrose (TCBS) agar medium. A rapid oxidase test procedure is described here. This takes 1 min, avoids false negative results and the necessity to grow the bacteria in a general-purpose medium. The bacteria may be recovered after the test and used for further investigations.
Culture Media↗
Nocturnal prolactin and growth hormone levels in children with complex partial and generalized tonic-clonic seizures.
This study measures whether there is a rise in the secretion of nocturnal prolactin and growth hormone (GH), during the delta phase of the first sleep cycle in children who are suffering from either complex partial or generalized tonic-clonic seizures. The findings are compared with those obtained in the control group of patients which is made up who suffer from pseudoseizures. There is a moderate but significant rise in the nocturnal prolactin plasma level in both types of infantile seizures. No significant difference was found in the GH.
Child↗
Oxygen radicals, enzymes, and fluid transport through pericardial interstitium.
The interstitium is the final link in the transportation of nutrients from the bloodstream to the individual cells of an organism. To assess interstitial fluid transport in normal and inflamed tissue, the hydration (H, ml H2O/g dry wt) and hydraulic conductivity (Kp, 10(-8) cm2.s-1.cmH2O-1) of bovine pericardial stroma were determined. The effect of enzymes and neutrophil-derived products of inflammation on the properties of the interstitial model were determined. Samples of the pericardium were exposed separately to trypsin, elastase, hyaluronidase, collagenase, superoxide radicals, and hydrogen peroxide. After exposure, the tissues were washed repeatedly in physiological saline and equilibrated in transport chambers heated to 37 degrees C and pressurized to 50 cmH2O. Fluid flow across the tissues was monitored. A section of tissue was removed and weighed. The tissue section was subsequently dried and reweighed. Tissue thickness, H, and Kp were calculated. H and Kp of the control tissues were 2.82 +/- 0.04 and 1.71 +/- 0.07, respectively. Hydration was significantly increased (22-38%) by exposure to trypsin, elastase, collagenase, and superoxide radicals. Kp increased significantly (30-1055%) in the groups treated with trypsin, hyaluronidase, collagenase, and superoxide radicals. The inflammatory mediators generally increased the hydration and/or the hydraulic conductivity of the model. These results indicate that neutrophil-derived products could be involved in the development of interstitial edema during the inflammatory process.
Animals↗
[Evaluation of blood esterases in Alzheimer's disease].
The aim of this work was to evaluate a possible correlation between erythrocyte acetylcholinesterase activity (AChE) and membrane fluidity expressed by fluorescence polarization of--1,6--diphenyl 1,3,5--hexatriene (DPH). Blood samples of 34 Alzheimer's patients (18F and 16M) were obtained and haemoglobin concentration, haematocrit, plasma (butyrylcholinesterase, BuChE) and erythrocyte (AChE) esterase activities and fluorescence polarization after introduction of DPH in erythrocyte membrane have been determined. Results were compared with values obtained from blood samples of 34 apparently healthy volunteers with the same age variation (53-82 years). There was no correlation between AChE activity and fluorescence polarization in the control group nor in the patients' group. There was a significant negative correlation (r = -0.82; p < 0.001) between mean corpuscular hemoglobin concentration (MCHG) and erythrocyte acetylcholinesterase activity in Alzheimer's patients. This correlation suggests that any variation of internal globular viscosity (or MCHG) may indirectly affect AChE enzymatic activity and consequently contribute to the loss of interrelation between AChE activity and membrane lipid fluidity, verified in the present work. A biological marker for Alzheimer's disease diagnosis remains to be discovered.
Acetylcholinesterase↗
[Renal dysplasia: clinico-pathologic review].
Histology records from 63 nephrectomies were reviewed; 22 patients had unilateral totally dysplastic kidneys and 5 had polar or segmental dysplasia. A clinicopathological study of these cases was undertaken. In the first group, there was a slight male preponderance and 75% of the patients presented were under two years of age. Urinary tract infection was the most common complaint. 4 patients were diagnosed in utero by ultrasound and 5 infants presented an abdominal mass. Hypertension was documented in a newborn baby. Ipsilateral lower urinary tract anomalies were found in 12 patients and those of the contralateral kidney in 2 children. There were 3 cases of extrarenal anomalies. Histological examination revealed 13 cases of multicystic dysplasia and 9 of solid dysplasia. Metaplastic cartilage was found in 1 case. In the group of segmental dysplasia, age ranging from 27 weeks' gestation to 8 years, at the time of the diagnosis. They all had duplex kidneys and 4 had ureterocele. Histological study in these cases was similar to the one found in the previous series, although superimposed inflammatory changes were more pronounced. Some of the theories regarding the pathogenesis of this disorder are reviewed and the importance of its diagnosis is emphasised.
Child↗
[Brain aging and dementia].
It is common knowledge that the base of the demographic pyramide is turning upwards as a consequence of the constant growing of the elderly population. This phenomenon worries everybody from families to government agencies. As a consequence, neuroscientists have been asked to cooperate for a better understanding of the problem related with the aging of the nervous system. Essentially they try to better grasp the mechanism of aging and their deleterious effects on the brain and how to fight the diseases of the nervous system with particular affinity for the aged people. We know that brain goes through morphological and biochemical changes with the passing of the years; it loses weight, microscopic changes occur and the activity of many neurotransmitters diminishes. In this context it is strange that some people still argue against the enfeeblement of the mental faculties with aging. Of all diseases of the nervous system tormenting the aged, the most common are depression and dementia. Most cases of depression and some forms of dementia are treatable but Alzheimer's disease, which afflicts a considerable percentage of old people, leading to greater psychological decline and leaving doctors helpless to halt it's unavoidable progress, is certainly the most dreaded old age mental sickness. The etiology of Alzheimer's disease is unknown. Under these circumstances several possibilities are investigated: genetic, infectious and toxic. Lately, investigators have focused their attention on amyloid, constitutive substance of the senile plaques one of the characteristic structural changes of the diseased brain. Nowadays there are studies on the relation between amyloid and a protein considered to be its precursor which has been found outside the nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Metabolism of platelet-activating factor in human haematopoietic cell lines. Differences between myeloid and lymphoid cells.
The binding and metabolism of platelet-activating factor (PAF) was studied in human cell lines resembling myeloid cells (HL60 and U937) and B and T lymphocytes (Daudi and Jurkat). All of the cell lines were found to bind and catabolize exogenous [3H]PAF in a time- and temperature-dependent manner. PAF binding could also be demonstrated in isolated membrane fractions, which provides further evidence of the existence of true membrane receptors. Myeloid cell lines contained numbers of receptors at least 10-fold higher than in lymphoid cell lines. Biosynthesis of PAF upon challenge by ionophore A23187 could be demonstrated in HL60 and U937 cells. In contrast, lymphoid cell lines were unable to produce PAF. Incubation with [14C]acetate showed incorporation of the label into three main fractions: neutral lipids, phosphatidylcholine and PAF, but the distribution of the label varied depending on the cell line. Significant incorporation into phosphatidylcholine was observed in uninduced myeloid cell lines. A phospholipase A2 acting on 1-O-hexadecyl-2-arachidonoyl-sn-glycero-3-phosphocholine and an acetyl-CoA:lyso-PAF acetyltransferase were expressed in the HL60 cell line and showed variations in specific activity with granulocytic differentiation. In contrast, these enzyme activities were not expressed in Daudi and Jurkat cell lines. These data indicate (1) the occurrence of PAF binding and catabolism in both myeloid and lymphoid cell lines; (2) the restriction of PAF biosynthesis to myeloid cell lines, especially HL60 cells; (3) the occurrence of differentiation-elicited changes in the specific activities of the enzymes involved in PAF biosynthesis by the remodelling pathway; and (4) the central role played by the disposal of lyso-PAF, a product of the phospholipase A2 reaction, in PAF biosynthesis.
Acetates↗
Gadolinium-DTPA MRI in the diagnosis of a patient with leptomeningeal metastasis produced by uvular carcinoma.
A patient with uvular cancer presented with lower limb weakness and paresthesiae, headache, neck stiffness and multiple cranial palsies. No malignant cells were found on lumbar puncture. CT, and MRI were normal. Gadolinium-DTPA MRI disclosed multiple enhancing lesions consistent with leptomeningeal metastases. Gd-DTPA MRI is the best technique to demonstrate tumoral meningeal infiltration in cytology-negative patients suspected of having leptomeningeal metastases.
Carcinoma, Squamous Cell↗
Synthesis of chiral and achiral pyranenamine derivatives. Potent agents with topical ocular antiallergic activity.
The SS, RR and meso stereoisomers of pyranenamine SK&F 84210 were synthesized stereospecifically starting from commercially available (R)-(-)- or (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol. In addition, two achiral pyranenamines 19 and 26 were also synthesized. When evaluated by intravenous and topical routes in the rat passive ocular anaphylaxis (POA) assay, (SS)- and meso-2 as well as achiral compounds 19 and 26 were found to be more potent antiallergic agents than (RR)-2.
Anaphylaxis↗
Blocking of periodontal afferents with anesthesia and its influence on elevator EMG activity.
The effect of anesthetic blocking of the periodontal afferents of the canine teeth was studied in order to determine its influence on any changes in the jaw elevation activity. Unilateral integrated EMG recordings were made of the masseter and anterior temporal muscles during maximal voluntary clenching in centric occlusion and laterotrusive position with canine contact. After anesthetic blocking of the periodontal afferents of one or both ipsilateral canines, a significant increase was observed of the EMG activity of both jaw elevator muscles studied, in centric occlusion as well as with canine contact. The elevator activity increase was of a greater magnitude when antagonistic canines were anesthetized. These findings thus support the hypothesis that high threshold periodontal receptors exert an inhibitory effect on jaw elevator muscular activity.
Adult↗
Calcium compartmentation and exchange rates in primary hepatocyte culture.
We utilized a technique, previously used to study myocardial cells (G. A. Langer, J. S. Frank, and L. M. Nudd, 1979, Amer. J. Physiol. 237, H239-H246), to study 45Ca2+ isotope exchange kinetics in hepatocyte monolayers, cultured on scintillation disks, and perfused in a flow-through chamber. Isolated rat hepatocytes were plated directly on Primaria-coated disks impregnated with scintillation fluors which made up the walls of the perfusion chamber. Following the labeling of the cells with radioactive calcium (45Ca2+), to apparent asymptote, the washout of 45Ca2+ from the cells was measured. A large very fast turnover compartment, as well as small fast and slow turnover compartments, were identified in each experiment. Surface calcium (Ca2+) was determined by its displacement with 1 mM La3+ after asymptote had been reached during 45Ca2+ labeling (1.59 mmol Ca2+/kg dry wt). The rate constant for this compartment was faster than the washout of the chamber (greater than 3.4 min-1 with a t1/2 less than 12 s). The rate constants for the fast and slow exchangeable compartments were 0.11 min-1 (t1/2 = 6.5 min) and 0.013 min-1 (t1/2 = 56 min), respectively. The fast compartment contained 0.40 mmol Ca2+/kg dry wt and the slow compartment contained 0.27 mmol Ca2+/kg dry wt. Neither the fast nor the slow compartment was lanthanum displaceable. Release of 45Ca2+ in response to 100 microM phenylephrine, 10 nM angiotensin II, and 100-microM 2,5-ditert-butyl hydroquinone was measured during the washout phase. Ca2+ released by these compounds was determined to be 0.50 mmol 0.44, and 0.43 mmol Ca2+/kg dry cell wt, respectively. These agents had an effect only during the washout of the fast compartment. In conclusion, this novel technique of on-line measurement of 45Ca2+ exchange in hepatocyte monolayers identified three exchangeable compartments: (1) a very rapidly exchangeable surface compartment, (2) a fast "microsomal" hormone-releasable compartment, and (3) a slow, non-hormone-releasable compartment.
Angiotensin II↗
Biosynthesis of platelet-activating factor (PAF) in human polymorphonuclear leucocytes. The role of lyso-PAF disposal and free arachidonic acid.
Theophylline and 1-methyl-3-isobutylxanthine (MIX), compounds that block eicosanoid formation and modulate phospholipase A2 activity, inhibited in a dose-dependent manner the formation of both leukotriene B4 (LTB4) and platelet-activating factor (PAF) by human polymorphonuclear leucocytes (PMN) in response to ionophore A23187. Theophylline and MIX lacked any inhibitory effect on acetyl-CoA: lyso-PAF acetyltransferase activity, which is the rate-limiting step for PAF biosynthesis in PMN. The effect of theophylline and MIX on PAF formation could be reversed by incubating the cells in the presence of 1-10 microM exogenous lyso-PAF. Incubation of PMN homogenates in the presence of unsaturated non-esterified fatty acids resulted in dose-dependent inhibition of the acetyltransferase. This effect was linked to the presence of a free carboxyl group, since both arachidonic acid methyl ester and palmitoyl-arachidonoyl phosphatidylcholine lacked inhibitory activity. This inhibitory effect was also dependent on the number of double bonds, since arachidonic acid (C20:4) and eicosapentaenoic acid (C20:5) displayed maximal effect. Kinetic analysis showed that the effect of arachidonic acid was consistent with competitive inhibition, with a Ki value of about 19 microM. Oxidative metabolites of arachidonic acid showed a lesser inhibitory effect with the following order of potency: arachidonic acid greater than 15-HETE (15-hydroxy-6,8,11,14-eicosatetraenoic acid) greater than LTB4 greater than 5-HETE (5-hydroxy-6,8,11,14-eicosatetraenoic acid) greater than lipoxin A4. Examination of enzymes involved in CoA-dependent acylation revealed a low activity of both arachidonoyl-CoA synthetase and arachidonoyl-CoA: lyso-PAF arachidonoyltransferase. These data indicate a strong influence on PAF biosynthesis of the products of the phospholipase A2 reaction, with lyso-PAF disposal being a critical event for PAF formation, and unsaturated fatty acids acting as feed-back inhibitors. The conversion of arachidonic acid via oxidative metabolism into less active inhibitors of acetyl-CoA:lyso-PAF acetyltransferase seems to be an additional mechanism of modulation of this enzyme activity, linked to the function of lipoxygenases. Finally, the enzyme activities involved in arachidonoyl-CoA-dependent acylation of lyso-PAF show a low efficiency in capturing arachidonic acid.
1-Methyl-3-isobutylxanthine↗