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At least 55 records · Page 3Linked to original sources

Antithrombin reduces ischemia/reperfusion-induced liver injury in rats by activation of cyclooxygenase-1.

This study was conducted to determine which isoform of cyclooxygenase (COX) is more significantly involved in the anti-thrombin (AT)-induced increase in prostaglandin production in the liver of rats, subjected to hepatic ischemia/reperfusion (I/R). Hepatic tissue levels of 6-keto-PGF(1alpha), a stable metabolite of prostacyclin (PGI(2)), and PGE(2) were transiently increased 1 hour after reperfusion. Thereafter, hepatic PGE2 levels were gradually increased until 6 hours after reperfusion, while hepatic 6-keto-PGF(1alpha) levels were decreased to the pre-ischemia levels at 6 hours after reperfusion. AT significantly enhanced increases in hepatic tissue levels of 6-keto-PGF(1alpha) and PGE(2) seen 1 hour after reperfusion, while it inhibited increases in hepatic PGE(2) levels seen 6 h after reperfusion. Neither dansyl-Glu-Gly-Arg-chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, nor Trp(49)-modified AT which lacks affinity for heparin, showed any effects on these changes. Pretreatment with indomethacin (IM), a non-selective inhibitor of COX, inhibited AT-induced increases in hepatic tissue levels of 6-keto-PGF(1alpha) and PGE(2) seen 1 hour after reperfusion, whereas pretreatment with NS-398, a selective inhibitor of COX-2, did not. The increase in hepatic tissue blood flow and inhibition of hepatic inflammatory responses seen in animals given AT were reversed by pretreatment with IM, but were not affected by pretreatment with NS-398. Administration of ilo-prost, a stable analog of PGI(2), and PGE(2) produced effects similar to those induced by AT. Increases in hepatic tissue levels of PGE(2) 6 hours after reperfusion were inhibited by pretreatment with NS-398. Although AT did not affect COX-1 mRNA levels 1 hour after reperfusion, it inhibited the I/R-induced increases in hepatic tissue levels of both PGE(2) and COX-2 mRNA 6 hours after reperfusion. These observations strongly suggested that AT might reduce the I/R-induced liver injury by increasing the production of PGI2 and PGE2 through activation of COX-1. Furthermore, since TNF-alpha is capable of inducing COX-2, inhibition of TNF-alpha production by AT might inhibit COX-2-mediated PGE(2) production. These effects induced by AT might contribute to its anti-inflammatory activity.

6-Ketoprostaglandin F1 alpha↗

[Localized hyperthermia of the prostate via the rectum in chronic inoperable urinary retention].

Local transrectal hyperthermia of the prostate was used to treat 16 poor surgical risk patients who had an indwelling catheter because of chronic urinary retention caused by benign prostatic hypertrophy. We used the Brucker (Prost-care) model with a rectal applicator, a water cooling system and a microwave generator operating at 915 MHz. Intraprostatic temperatures of 42 degrees to 44 degrees C were measured by a radiometric system. 12 patients received a complete treatment which consists in 6 to 10 sessions of one hour and was controlled at least one month later. 8 of them no longer need a catheter. Uroflowmetry was between 7.5 and 17.6 ml/sec and residual urine appreciate by ultrasounds was less than 60 cm3.

Aged↗

[Clinical usefulness of circulating tumor markers].

There are many molecular tumor markers for diagnosing and monitoring cancer patients. Especially, quantitative assay for serum levels of tumor markers; such as AFP, CEA, PSA, hCG, CA 19-9 and CA 125, are frequently used in daily practice because of their relative specificities and usefulness to the common cancers. Though not suitable for early diagnosis, but they are used in monitoring patients with advanced caner, especially after treatments. Two of them, AFP and PSA, are also used in the screening and monitoring of high-risk groups, namely patients with chronic viral hepatitis and old male, who are the high risk for hepatoma and proste cancer respectively. Problems in using serum markers are; relatively low specificity and low sensitivity to cancer, confusing naming for similar markers that recognize almost the same molecule of cancer. Users must understand that CA 19-9, CA 50, KM-O 1 and SPAN-1 are in the same sialylated Lewis A group, and CA 125, CA 130 and CA 602; in the mucin antigen group, and STN, CA 54/61 and CA 72-4; in the sialyl Tn antigen group. Combination of two or more markers may inform us the biological characteristics of the cancer. For example, a germ-cell tumors may produce hCG and placental marker. That is of the choriocarcinoma type. Those with hCG and fetal antigens are the ordinal type of germ cell tumors, and those with AFP, CEA and cytokeratin are teratoma, and those with LDH and ALP only but negative for hCG and AFP must be seminoma. For the bronchial and alveolar carcinomas, CEA, SCC, NSE and cytokeratin 19 fragments are useful. Combination may be difficult for beginners but once understood, it will be an art in clinical oncology.

Antigens, Neoplasm↗

[Coronary angioplasty: experience at the University Hospital of Madrid].

The results of 963 consecutive coronary angioplasties, with 1.135 lesions attempted in 816 patients, were prospectively analyzed. Initial angiographic success (residual stenosis less than 50%) was achieved in 1.017 lesions (89.6%), and final success was obtained in 838/963 procedures (87%). Major complications included: emergency surgery in 4 cases (0.4%), acute myocardial infarction in 28 (2.9%), and death during hospitalization in nine (0.9%). Surgical stand-by was required only for cases with vital risk should the attempted vessel occlude. This criteria was present in 230 (23.8%) angioplasties. Coronary angioplasty was performed during the diagnostic procedure in 300 (31.1%) case, with final success in 264 (88%) of them. A exercise test was achieved before the procedure in 419 (50%) successful angioplasties and in 246 (58.7%) of them it was abnormal because of angina (with or without ST depression). After procedure, exercise could be performed in 780 cases (93%), and the result remained unchanged in only 44 (5.6%) (p less than 0.01). At discharge 780 (93%) patients with final success considered themselves clinically improved. In our experience, coronary angioplasty is a good myocardial revascularization technique, with high success, low rate of major complications, and that provides a good clinical outcome. Surgical stand-by may be unnecessary in prost of angioplasty procedures if patients selection is carefully done, also, this approach makes it possible to perform angioplasty at time of diagnostic catheterization.

Adult↗

[Cicatricial pemphigoid disclosed by superficial desquamative gingivitis. Clinical and immuno-electron microscopic study of a case].

Six months before consulting, a 71-year old man developed buccal and genital erosions which gradually became worse. Physical examination showed signs of superficial desquamative gingivitis, wide erosions on the bony palate, erythemato-erosive balanoposthitis and 7 bullae or skin erosions on the upper part of the back. At histopathological examination of a cutaneous bulla there was dermoepidermal cleavage and an inflammatory infiltrate without eosinophils. At direct immunofluorescence, linear deposits of IgG and C3 were present along the basement membrane. A search for anti-skin autoantibodies was negative at indirect immunofluorescence but positive at immunoblotting (240 Kd band). The cicatricial pemphigoid was treated with dapsone alone in doses of 100 mg/day. Treatment was continued for 6 months, resulting in complete cure of the mucosal and cutaneous lesions. An immunoelectromicroscopic study, performed according to the technique described by Prost et al., on a fragment of skin from around the bullae, showed deposits of granular IgG in the lamina lucida and the lamina densa and deposits of C3 in the lamina densa. This case of cicatricial pemphigoid exhibited 3 features which are not usually found in bullous pemphigoid. Clinically, the buccal lesions were located on the gums and on the hard palate, i.e. where the mucosa adheres to the underlying bone through the periosteum. This location is habitual in cicatricial pemphigoid and differs from that of the bullous pemphigoid lesions which affect the free mucosa lining the cheeks and the soft palate. Treatment with dapsone was dramatically successful in our patient whose lesions disappeared in 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

An epidemiological study of selected calf pathogens on Holstein dairy farms in southwestern Ontario.

Fecal samples from calves on 78 randomly selected Holstein dairy farms in southwestern Ontario were screened for Salmonella, Campylobacter jejuni/coli, enteropathogenic Escherichia coli, rotavirus and coronavirus. Based on the observed prevalence, 22% of farms had calves infected with Salmonella, 13% with Campylobacter jejuni/coli, 41% with enteropathogenic E. coli, 19% with rotavirus and 5% with coronavirus. These estimates can be modified, using a method developed by Mullen and Prost (1983) for the World Health Organization, to account for the nature of the laboratory test used. If the test is assumed to have no false positives (that is, if an organism is detected it must be there), then the observed prevalence estimates seen on this study may greatly underestimate the true prevalence of infected premises. The use of nipple feeders for calves was associated with an increased probability of farms having calves shedding detectable fecal levels of Salmonella, E. coli, or one of the two viruses. The use of group pens was associated with an increased odds of finding C. jejuni. Calves with diarrhea on these farms tended to have increased odds of shedding rotavirus, and E. coli with the K99 antigen. However, at the farm level, none of the organisms was associated with above median levels of morbidity. Farms positive for one or other of the viruses had increased odds of experiencing calf mortality relative to virus-negative farms, and farms positive for C. jejuni/coli had decreased odds of mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Action of MDL 646, a new synthetic prostaglandin, on gastric acid secretion of some experimental animals.

The new synthetic prostaglandin 11,15-dihydroxy-16-methyl-16-methoxy-9-oxo-prost-13-en-1-oic acid,methyl ester (8 alpha,11 alpha,15R,16R) (compound marked MDL 646), belonging to the 16-methyl-16-methoxy series, was tested for its activity on gastric secretion of different animal species and in different experimental conditions. In the dog provided with gastric fistula and Heidenhain pouch, MDL 646 (25 micrograms/kg by intragastric administration) caused a remarkable inhibition of the histamine- and bethanechol-induced acid secretion, an effect which was more evident in the main stomach than on the Heidenhain pouch. In the cat, but not in the dog, the compound inhibited not only the hypersecretion induced by histamine and bethanechol but also that induced by pentagastrin. However, in this case, high doses (50-100 micrograms/kg) had to be used to obtain a significant inhibition. Similar results were obtained with the perfused stomach of the anaesthetized rat in which the natural PGE2 appeared to be from 3 to 5 times less potent. In the conscious rat provided with gastric fistula MDL 646 (15 and 50 micrograms/kg) significantly inhibited spontaneous gastric secretion. Untoward reactions, represented by salivation and vomiting lasting 30 min, were experienced by some dogs following administration of 50-100 micrograms/kg of the synthetic prostaglandin. These data appear of considerable interest in view of the possibility of the use of MDL 646 also in humans.

Alprostadil↗

[Spirit and madness. The Maison Blanche at Montmartre].

Dr Prost's psychiatric clinic was managed by the doctors Blanche senior and junior (Esprit and Emile), then by doctors Meuriot senior and junior during more than one century from Napoleon's First Empire until the end of the first world war (1914-1918). This clinic acquired a sound reputation and celebrity thanks to the use of new psychiatric methods and a practice open to all artists and literary elite at that time, with whom the successive owners kept friendly relationships.

Ambulatory Care Facilities↗

Factors affecting the incidence of polyploidy in a human in vitro fertilization program.

OBJECTIVE: To study the factors affecting the incidence of polyploidy in an assisted reproduction program. DESIGN: Retrospective analysis. SETTING: University-based subfertility clinic. PATIENTS AND METHODS: Subfertile patients were treated in 163 treatment cycles of in vitro fertilization (IVF) or pronuclear stage tubal transfer (PROST). The relationship between the incidence of polyspermy and the indication of subfertility, the stimulation protocol, the oocyte, and the semen parameters were analyzed. RESULTS: Eighty-nine of the 1,149 oocytes were polyploid (7.8%). The incidence of polyploidy was not affected by the indication for IVF, the age of the patients, the stimulation protocol, the maturity of oocytes as assessed by the appearance of the cumulus, the sperm concentration, the number of sperm inseminated, the serum estradiol level, and the number of oocytes retrieved. The incidence was increased when: (1) the serum estradiol fell before the administration of human chorionic gonadotrophin; (2) the oocyte retrieval-insemination interval was 6 hours or more; (3) the sperm motility was 70% or more; (4) the percentage of sperm with normal morphology was 50% or more. CONCLUSION: The incidence of polyploidy was affected by the serum estradiol pattern, the preinsemination interval, sperm motility, and percentage of morphologically normal sperm.

Adult↗

Three severe cases of EBS Dowling-Meara caused by missense and frameshift mutations in the keratin 14 gene.

We report three unrelated patients affected at birth with an unusually severe form of epidermolysis bullosa simplex Dowling-Meara type (EBS-DM) because of mutations in KRT14 encoding keratin 14. Two patients were heterozygous for the previously described p.M119T mutation. The third patient was heterozygous for a novel c.1246delC mutation predicting the replacement of the helix termination peptide and the tail domain by a 25 amino-acid aberrant carboxyterminal sequence. At age 2 years, patients carrying the p.M119T mutation still suffered from severe EBS-DM, whereas the patient harboring the c.1246delC mutation has improved over time. These cases illustrate genotype-phenotype correlations and have implications for genetic counselling of EBS.

Child, Preschool↗

Homozygosity mapping of a locus for a novel syndromic ichthyosis to chromosome 3q27-q28.

Ichthyosis is a heterogeneous group of skin disorders characterized by abnormal epidermal scaling. Occasionally, extracutaneous features are associated. A novel autosomal recessive ichthyosis syndrome is described here with scalp hypotrichosis, scarring alopecia, sclerosing cholangitis, and leukocyte vacuolization in two inbred kindreds of Moroccan origin. We also report the mapping of the diseased gene to a 21.2 cM interval of chromosome 3q27-q28. Homo zygosity for polymorphic markers has enabled us to reduce the genetic interval to a 16.2 cM region. Furthermore, comparison of mutant chromosomes in the two families has suggested a common ancestral mutant haplotype. This linkage disequilibrium has reduced the genetic interval encompassing the diseased gene to less than 9.5 cM maximum. Further study of additional families from the same geographic area will hopefully reduce the genetic interval as well as help in the cloning of the gene involved in this rare disorder.

Adolescent↗

Deletions within COL7A1 exons distant from consensus splice sites alter splicing and produce shortened polypeptides in dominant dystrophic epidermolysis bullosa.

We describe two familial cases of dominant dystrophic epidermolysis bullosa (DDEB) that are heterozygous for deletions in COL7A1 that alter splicing, despite intact consensus splice-site sequences. One patient shows a 28-bp genomic deletion (6081del28) in exon 73 associated with the activation of a cryptic donor splice site within this exon; the combination of both defects restores the phase and replaces the last 11 Gly-X-Y repeats of exon 73 by a noncollagenous sequence, Glu-Ser-Leu. The second patient demonstrates a 27-bp deletion in exon 87 (6847del27), causing in-frame skipping of this exon; consensus splice sites, putative branch sites, and introns flanking exons 73 and 87 showed a normal sequence. Keratinocytes from the probands synthesized normal and shortened type VII collagen polypeptides and showed intracellular accumulation of type VII procollagen molecules. This first report of genomic deletions in COL7A1 in DDEB suggests a role for exonic sequences in the control of splicing of COL7A1 pre-mRNA and provides evidence that shortened type VII collagen polypeptides can alter, in a dominant manner, anchoring-fibril formation and can cause DDEB of differing severity.

Adult↗

Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation.

We have characterized 21 mutations in the type VII collagen gene (COL7A1) encoding the anchoring fibrils, 18 of which were not previously reported, in patients from 15 unrelated families with recessive dystrophic epidermolysis bullosa (RDEB). COL7A1 mutations in both alleles were identified by screening the 118 exons of COL7A1 and flanking intron regions. Fourteen mutations created premature termination codons (PTCs) and consisted of nonsense mutations, small insertions, deletions, and splice-site mutations. A further seven mutations predicted glycine or arginine substitutions in the collagenous domain of the molecule. Two mutations were found in more than one family reported in this study, and six of the seven missense mutations showed clustering within exons 72-74 next to the hinge region of the protein. Patients who were homozygous or compound heterozygotes for mutations leading to PTCs displayed both absence or drastic reduction of COL7A1 transcripts and undetectable type VII collagen protein in skin. In contrast, missense mutations were associated with clearly detectable COL7A1 transcripts and with normal or reduced expression of type VII collagen protein at the dermo/epidermal junction. Our results provide evidence for at least two distinct molecular mechanisms underlying defective anchoring fibril formation in RDEB: one involving PTCs leading to mRNA instability and absence of protein synthesis, the other implicating missense mutations resulting in the synthesis of type VII collagen polypeptide with decreased stability and/or altered function. Genotype-phenotype correlations suggested that the nature and location of these mutations are important determinants of the disease phenotype and showed evidence for interfamilial phenotypic variability.

Alleles↗

A polyunsaturated fatty acid diet lowers blood pressure and improves antioxidant status in spontaneously hypertensive rats.

gamma-Linolenic acid [GLA, 18:3(n-6)], eicosapentaenoic acid [EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)] have been reported to prevent cardiovascular diseases. However, they are highly unsaturated and therefore more sensitive to oxidation damage. We investigated the effects of a diet rich in these polyunsaturated fatty acids (PUFA) on blood pressure, plasma and lipoprotein lipid concentrations, total antioxidant status, lipid peroxidation and platelet function in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Five-week-old SHR and WKY rats were fed for 10 wk either a diet containing Isio 4 oil or a diet rich in GLA, EPA and DHA (5.65, 6.39 and 4.94 g/kg dry diet, respectively). The total antioxidant status was assayed by monitoring the rate of free radical-induced hemolysis. VLDL-LDL sensitivity to copper-induced lipid peroxidation was determined as the production of thiobarbituric acid reactive substances. After dietary PUFA supplementation, a significant decrease in blood pressure of SHR rats (-20 mm Hg) was observed and the total antioxidant status was enhanced. VLDL-LDL resistance to copper-induced peroxidation was increased in both strains. The PUFA supplementation did not change platelet maximum aggregation in SHR rats, but it decreased the aggregation speed. In hypertensive rats, GLA + EPA + DHA supplementation lowers blood pressure, enhances total anti-oxidant status and resistance to lipid peroxidation, diminishes platelet aggregation speed and lowers plasma lipid concentrations. Thus, it enhances protection against cardiovascular diseases. Therefore, nutritional recommendations for cardiovascular disease prevention should take into account the pharmacologic properties of GLA, EPA and DHA.

Animals↗

Tissue antioxidant status differs in spontaneously hypertensive rats fed fish protein or casein.

The present study was designed to determine whether changes in dietary protein source are related to changes in antioxidant status determined by enzyme activities of catalase, superoxide dismutase (SOD), gluthatione peroxidase (GSH-Px) and gluthatione reductase (GSSG-Red) and lipid peroxidation levels in various tissues. Spontaneously hypertensive rats (SHR; 5 wk old) were fed diets containing 20% casein or fish protein for 2 mo. Feeding the fish protein diet lowered blood pressure and reduced plasma total cholesterol levels and SOD activity in all tissues except muscle compared with the casein diet. Feeding fish protein also enhanced GSH level and GSH-Px activity in liver and heart, accompanied by lower lipid peroxidation. In kidney, however, the lower catalase activity in rats fed fish protein was associated with an enhancement in lipid peroxidation. Plasma and VLDL + LDL lipid peroxidation was unaffected by dietary proteins. In conclusion, the fish protein diet did not play a relevant role in plasma antioxidative defense status but increased it in liver and heart compared with the casein diet. Fish protein attenuated the development of hypertension and also decreased plasma total cholesterol concentration. Thus, it enhances protection against cardiovascular diseases.

Adipose Tissue↗

[Functional results in children with retinopathy of prematurity stage 4 and 5].

AIM OF THE PAPER: To investigate the structural and functional results in children with retinopathy of prematurity stage 4 and 5. MATERIAL AND METHODS: 91 children with ROP stage 4 and 5 were observed by the authors in years 1990-1998. In all patients the clinical course of the disease, visual acuity and binocular vision were examined during follow-up. RESULTS: Most patients with ROP stage 4 and 5 are blind or practically blind, even the children in whom only stage 4a was diagnosed. CONCLUSION: Prognosis for vision in children with ROP stage 4 and 5 is poor and all methods of surgical treatment of retinal detachment should be performed in these children to safeguard some kind of useful vision in some patients.

Child, Preschool↗

Very high alpha-tocopherol diet diminishes oxidative stress and hypercoagulation in hypertensive rats but not in normotensive rats.

BACKGROUND: Oxidative stress is closely related to cardiovascular diseases, such as atherosclerosis. Increasing dietary antioxidants, such as alpha-tocopherol, may prevent these diseases. However, in some pathologies, such as hypertension, oxidative stress is enhanced, thus alpha-tocopherol requirements may be raised. MATERIAL/METHODS: In eleven-week-old spontaneously hypertensive rats and normotensive Wistar Kyoto rats, we investigated the effects of a four-week very high alpha-tocopherol dietary enrichment (1,200 mg/kg diet, VH) on blood pressure, resistance to free radical aggression, and VLDL+LDL resistance to lipid peroxidation. Platelet aggregation and plasma lipid profile were also investigated. RESULTS: With either diet, hypertensive rats were more protected against oxidative stress than normotensive rats. Their capacity to withstand free radical aggression was better, and their VLDL+LDL particles were less sensitive to lipid peroxidation. In either group, the VH diet did not modify blood pressure values when resistance to free radical aggression was increased, but not the resistance of VLDL+LDL to lipid peroxidation. With the control diet, platelet aggregation was faster and higher in hypertensive rats vs. normotensive rats. It was decreased with the VH diet in hypertensive rats but increased in normotensive rats, when compared to their respective controls. Whatever the diet, plasma triacylglycerol, phospholipid and cholesterol concentrations were lower in hypertensive than in normotensive rats. Only cholesterol concentrations were diminished with the VH diet in hypertensive rats, but not in normotensive rats. CONCLUSIONS: These results indicate that very high alpha-tocopherol dietary amounts decrease cardiovascular risk in hypertensive rats with high oxidative stress, but have less effect on normotensive rats.

Animals↗