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Biomedical subjects

N Salem

Publications and source records attributed to N Salem.

179 records · Page 10Linked to original sources
PubMed1977

Enhancement of opiate binding by various molecular forms of phosphatidylserine and inhibition by other unsaturated lipids.

A study was undertaken on the possible involvement of phospholipids on stereospecific opiate binding to a rat brain membrane fraction comprised mainly of synaptic membranes. The addition of acidic phospholipids such as phosphatidylserine, phosphoinositides, and phosphatidic acid significantly enhanced opiate binding. With the exception of phosphatidylserine, when the acidic phospholipids contained a polyunsaturated acyl group, they were actually inhibitory, along with neutral phospholipids derived from brain. Both the C18:0, C18:1 form (derived from myelin) and the C18:0, C22:6 form of phosphatidylserine (derived from synaptic membranes) produced as much as a 45% enhancement in opiate binding. Unsaturated fatty acids were highly inhibitory, the degree of inhibition being related to the degree of unsaturation. Both phospholipase A and C were inhibitory; and the inhibitory effect of A could not be prevented by albumin or overcome with the addition of phosphatidylserine. With the use of the cross-linking agent, dinitrodifluorobenzene, it could be demonstrated that the phosphatidylserine of synaptic membranes appeared to be preferentially associated with membrane protein. The enhancement of opiate binding by phosphatidylserine diminished with increasing degree of cross-linking.

Animals↗
PubMedDate not supplied

In vivo conversion of linoleic acid to arachidonic acid in human adults.

Human adults are shown to be capable of conversion of linoleic acid (LA, 18:2 n-6) to arachidonic acid (AA, 20:4 n-6) in vivo. It is confirmed that they can also convert alpha-linolenic acid (LNA, 18:3 n-3) to eicosapentaenoic acid (EPA, 20:5 n-3) and to docosahexaenoic acid (DHA, 22:6 n-3) in vivo. The time course and the maximal response for these processes during the first week after a single dose of the 18-carbon precursor is described. A stable-isotope method in which the protons of the C17 and C18 carbons are substituted with deuterium atoms is used in order to provide for a safe method for the study of human metabolism. High sensitivity and selectivity of detection is assured with negative ion, gas chromatography/mass spectrometry analysis. It is clear that human adults on an ad lib diet carry out EFA metabolism in vivo.

Administration, Oral↗
PubMedDate not supplied

[Treatment of A2-B2 prostatic cancer: results of a hormonoradiotherapy combination in the PSA era].

PURPOSE: Prospective analysis of results of combined neoadjuvant hormonetherapy and external beam radiation therapy in A2-B2 prostate adenocarcinoma. PATIENTS AND METHODS: Between 1986 and 1994, 36 patients with clinical stage A2 (five patients), B1 (12 patients) and B2 (19 patients) N0 adenocarcinoma of the prostate declined for radical surgery, underwent a brief neoadjuvant hormonal therapy before external beam radiotherapy at our radiation therapy department. They all had a PSA determination before the combined treatment and no evidence of local extension or metastatic spread. They were followed clinically and with serial PSA levels for a median time of 58 months. Relapse was defined by a PSA level > or = 2.5 ng/mL. RESULTS: Median pre-treatment PSA level was 16.5 ng/mL; 16 patients had less than 15 ng/mL. Combined treatment was very well tolerated. After 3 months of neoadjuvant hormonetherapy, digital rectal examination was normalized in 27 cases with a PSA value < or = 1 ng/mL in 23. Only four tumors have relapsed (one local failure, two metastases and one PSA failure). The single factor that predicted biochemical relapse was pre-treatment PSA level: the 5-year actuarial rate of PSA failure when PSA level < 15 ng/mL was 0% and 27.5% if it was > or = 15 ng/mL (p = 0.05). During follow-up, only two patients suffered grade 2 rectitis and seven complained a total impotency. CONCLUSION: This limited study advocates hormonal neoadjuvant therapy and radiotherapy association in intracapsular prostatic carcinoma in patients declined for surgery or when pre-treatment PSA is above 15 ng/mL, with mild acute and late toxicity.

Aged↗
PubMedDate not supplied

[Clinical and biological evaluation of the response to neoadjuvant hormone therapy before radiotherapy in nonmetastatic cancers of the prostate].

PURPOSE: The aim of this study was to evaluate the clinical and biochemical response to neoadjuvant hormonal therapy (NAHT) before radical external radiotherapy (EBRT). MATERIALS AND METHODS: From June 1986 to June 1994, 105 patients with histologically proven and non-metastatic prostate adenocarcinoma (stage B2-C2) received a short induction hormonal therapy (median: 3 months) with a luteinizing hormone releasing hormone (LHRH) analog associated with an anti-androgen followed in all cases by EBRT (66 Gy). All patients underwent a prostate-specific acid (PSA) determination, pelvic computed tomography (CT) scan and bone scan before the combined treatment. Response, treatment toxicity and PSA concentration were analyzed after the NAHT, 3 months after the completion of radiotherapy and every 6 months there after. Relapse was defined by PSA elevations above 4 ng/mL or two consecutive elevation above 1 ng/mL. RESULTS: Median follow-up was 52 months. According to the Withmore-Jewett clinical classification, 85 tumors were stage C. Pre-treatment PSA (PSAi) was above 20 ng/mL in 63.8% of the patients (median PSAi: 26 ng/mL). A clinical evaluation and a PSA determination (PSAPH) were both performed for all patients after NAHT. Most of the time, urinary obstructive symptoms disappeared with androgen ablation; tumor volume regression exceeded 50% in 99 cases and was complete in 50 cases. Median PSAPH was 0.6 ng/mL for the entire group. Clinical and biochemical tumor response were coherent: 84% of patients with clinical total remission had a PSAPH < 1 ng/mL. PSAPH value was significantly correlated with tumor stage and pre-treatment PSAi: among the 11 patients with a PSAPH > 4 ng/mL, ten were stage C and nine had a PSAi > 20 ng/mL. A PSAPH value exceeding 4 ng/mL predicted biochemical relapse (P < 0.0001). CONCLUSION: We conclude that biochemical response to hormonal therapy has a major prognostic value before EBRT can help to identify patients for an adjuvant hormonal therapy.

Adenocarcinoma↗
PubMedDate not supplied

A sensorineural progressive autosomal recessive form of isolated deafness, DFNB13, maps to chromosome 7q34-q36.

Deafness is the most frequent sensorineural defect in children. The vast majority of the prelingual forms of isolated deafness are highly genetically heterogeneous with an autosomal recessive mode of inheritance. Using linkage analysis, we have mapped the gene responsible for a severe progressive sensorineural hearing loss, DFNB13, segregating in a large consanguineous family living in an isolated region in northern Lebanon. A maximum lod score of 4.5 was detected for markers D7S661-D7S498. Recombination events and homozygosity mapping by descent define a 17 cM gene interval in the chromosome region 7q34-q36, between the markers D7S2468/D7S2505, on the proximal side, and D7S2439, on the distal side.

Chromosome Mapping↗
PubMedDate not supplied

Identification of a locus on chromosome 7q31, DFNB14, responsible for prelingual sensorineural non-syndromic deafness.

In our efforts to identify new loci responsible for non-syndromic autosomal recessive forms of deafness, DFNB loci, we have pursued the analysis of large consanguineous affected families living in geographically isolated areas. Here, we report on the study of a Lebanese family affected with a prelingual profound sensorineural isolated form of deafness. Segregation analysis resulted in a linkage with locus D7S554 to locus D7S2459 on 7q31, with a maximum lod score of 6.3. The causative gene was mapped to a 15 cM interval extending from D7S527 to D7S3074 (on the telomeric side). The distal limit of this interval could be located between D7S496 and D7S3074 which are the closest polymorphic loci flanking the gene underlying Pendred syndrome (PDS) on the centromeric and on the telomeric sides, respectively. To eliminate PDS as a candidate gene, its 21 exons were sequenced. No mutation was detected. This study therefore reports the identification of a novel locus, DFNB14, on chromosome 7q31, in a position proximal to PDS.

Audiometry↗
PubMedDate not supplied

A technique for the in vivo study of multiple stable isotope-labeled essential fatty acids.

A novel tracer technique is presented for the simultaneous and independent measurement of multiple stable isotopically labeled essential fatty acids. Gas chromatography/negative chemical ionization mass spectrometry was employed for high sensitivity detection of the following isotopes: deuterium-labeled-linolenate, carbon-13-U-labeled-eicosapentaenoate, carbon-13-U-labeled-linoleate, and deuterium-labeled-dihomo-gamma-linolenate. These isotope-labeled fatty acids in vehicle oil were given to rats either singly or together as a single oral dose. Rat blood was collected after dosing and the isotopomers of the precursors and their main metabolites, including those containing both(13) C and (2)H, were detected simultaneously with good resolution and without interference from other isotopes due to differences in mass and chromatographic retention.

Administration, Oral↗
PubMedDate not supplied

Effects of acute and chronic ethanol exposure on the response of rat aorta to a thromboxane mimic, U46619.

The spasmogenic properties of a stable thromboxane mimic, U46619, were determined in the isolated rat aorta after 1, 4, 8, or 12 hr of acute ethanol exposure in vitro or after 12 days of chronic exposure by inhalation. Acute ethanol exposure (87-822 mM) increased the baseline tension of aortic rings in a concentration-dependent manner. Moderate concentrations of ethanol (11 and 43 mM) decreased the maximum tensile response of rat aortic rings to U46619 after 8 and 4 hr of exposure, respectively. In contrast, higher ethanol concentrations (87 and 411 mM) did not significantly effect the maximum tensile response to U46619. Ethanol at 822 mM completely inhibited the response to U46619 and this inhibition could be 85% reversed after removal of ethanol. The inhibitory effect of 1.64 M ethanol was irreversible. Sensitivity to U46619 was inversely related to the ethanol concentration (greater than or equal to 43 mM) and incubation time. Similarly, chronic exposure to moderate blood ethanol levels (92-198 mg/100 ml) for 12 days decreased the maximum tensile response whereas high levels did not effect aortic contractility in vitro. Sensitivity of aorta from rats with mean blood ethanol levels greater than or equal to 92 mg/100 ml decreased at least one order of magnitude. The results suggest that the effect of physiologically tolerable ethanol concentrations on the amplitude of the tensile response to U46619 is biphasic both during acute exposure in vitro or following a chronic exposure period in vivo and the inhibitory effect on sensitivity for U46619 is both concentration- and time-dependent in the rat aorta preparation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMedDate not supplied

Alterations in brain function after loss of docosahexaenoate due to dietary restriction of n-3 fatty acids.

The concentration of the major polyunsaturated fatty acid (PUFA) in brain, docosahexaenoate, may be markedly reduced by two or more generations of dietary restriction of sources of n-3 fatty acids in the diet. Such a deficiency was induced through the feeding of safflower oil as the principal source of essential fatty acids. The reference point for this diet was an n-3 adequate diet to which alpha-linoleate and docosahexaenoate were added through the addition of a small quantity of flax seed or algael oils, respectively. The loss of brain DHA was associated with poorer performance in spatial tasks and an olfactory-cued reversal learning task. No difference could be observed in the hippocampal gross morphology. This study demonstrates the importance of providing a source of n-3 fatty acids during mammalian growth and development.

Animals↗
PubMedDate not supplied

Insulin secretion decline unrelated to jejunal morphology or exocrine pancreatic function in children with celiac disease.

We describe a prospective 10-year study of insulin secretion and immunologic changes in a group of children with celiac disease (CD) on a gluten-free diet. Thirty CD patients aged 4-16 years and 30 matched controls were examined. They underwent i.v. glucose tolerance test during which glucose disappearance rate (K) and first phase insulin response (FPIR) were measured. Typing for HLA A, B, C, and DR antigens was performed and sera were analyzed for cytoplasmic islet cell antibodies (ICA) on several occasions. Pancreatic isoamylase (PIA) was measured to assess exocrine pancreatic function. In 4/21 CD children, FPIR and K rate were decreased. There was a significant correlation between the two parameters (p < 0.01). The incidence of HLA B8 and DR3 was higher in CD (33% and 60%, respectively) than in healthy individuals (p < 0.001). All patients were found to be ICA negative at the time of the study and at follow-up. There was no correlation between parameters of endocrine (FPIR, K) and exocrine (PIA) pancreatic function. One out of four children with reduced FPIR developed overt DM during the study. In conclusion, the decline of first phase insulin secretion documented in CD patients is unrelated to jejunal morphology or exocrine pancreatic function. This decline may be an expression of a prediabetic phase as observed in one of the subjects who finally developed IDDM. HLA B8 and DR3, which are detected in celiac patients, may indicate a possible common pathogenic mechanism between CD and IDDM.

Adolescent↗
PubMedDate not supplied

The nervous system has an absolute molecular species requirement for proper function.

A considerable body of biological evidence has accumulated that suggests that docosahexaenoic acid (22:6n3) is an essential component in the nervous system. Moreover, it appears from these studies that long chain polyunsaturates of the n-6 family such as arachidonate (20:4n6) and docosapentaenoate (22:5n6) cannot substitute for 22:6n3. This evidence is briefly reviewed and two hypotheses centering upon either biochemical or biophysical aspects of polyunsaturate function are presented and discussed. It is concluded that a bioactive metabolite of 22:6n3 is not responsible for its function in brain and that the best hypothesis asserts that a membrane function of a 22:6n3-containing species of phospholipid, such as phosphatidylserine, is critical for optimal neural function. Moreover, data are presented indicating that the biophysical properties of various highly unsaturated species of phospholipid are distinguishable. It is further contended that these species are not randomly distributed in membranes and thus the differences in physical properties may be amplified. It is concluded that a conceptual framework is needed in which the distinct membrane roles of phospholipid species may be understood as a function of the positions and numbers of double bonds. Only then may the critical role of the highly unsaturated n-3 polyunsaturates in the brain and retina be understood.

Animals↗
PubMedDate not supplied

[Hereditary sideroblastic anemia: a rare diagnosis].

Hereditary sideroblastic anemia is a very rare disease recessive and X-linked that affect heme biosynthesis by deficit or decreased of delta aminolevulinic acid synthase (ALAS) activity. We report a case of a six-month-old boy, admitted in the hospital for anemic syndrome. The hemogram showed anemia (hemoglobin: 4.5 g/dL), frankly hypochronic microcytic and a regenerated (mean corpuscular hemoglobin concentration: 26 g/dL, mean cell volume: 53 fl, reticulocytes: 10 x 10(9)/L) with red cells morphologic disorders in smears (anisopoikylocytosis) without attack of the other lineages; white blood cells: 11 x 10(9)/L (neutrophils: 64% and lymphocytes: 35%); platelets: 350 x 10(9)/L. Examination of bone marrow showed an important erythroid hyperplasia (about 69%) with dyserythropoiesis. Perls stain revealed intense siderosis with 90% of ringed sideroblasts and a large number of siderocytes. Exploration of ALAS2 and ABC7 genes on the DNA of the infant was not found abnormalities. Treatment with pyridoxine corrects moderately the anemia. By the way, we proposed to remind that iron deficiency, inflammatory syndrome and thalassemia are the common microcytic anemia. However, it's mandatory to explore other causes if diagnosis is not solved.

Anemia, Sideroblastic↗
PubMedDate not supplied

Cardiotoxicity evaluation in patients treated with a mitoxantrone combination as adjuvant chemotherapy for breast cancer.

Indices of cardiac function were measured in 49 women who received adjuvant treatment for stage II breast cancer. The combination chemotherapy consisted of six monthly courses of cyclophosphamide, 500 mg/m2, mitoxantrone, 10 mg/m2 and fluorouracil, 500 mg/m2 (CNF). Left ventricular function was assessed by echocardiography, systolic time intervals and nuclear angiography. The values of the echocardiographic left ventricular end diastolic diameter (Dd) and end systolic diameter (Ds), and those of the index of preejection period (PEPI) and the ratio of the preejection period to left ventricular ejection time (PEP/LVET), determined in 41 patients before chemotherapy, at midcourse and after chemotherapy by echocardiography and systolic time intervals (STI), showed a slight but significant increase. All these values remained within normal limits. Resting nuclear angiography, performed before and after treatment, showed a decrease in LVEF by 10% or more in four patients; the postchemotherapy values remained within the normal range in all cases. In conclusion, adjuvant treatment of breast cancer patients with 6 cycles of the CNF combination, as judged by its effect on the measured indices, does not appear to be cardiotoxic.

Adult↗
PubMedDate not supplied

[Blood and leukocyte glutathione and glutathione S-transferase: relationship to cholesterolemia in healthy volunteers].

Hypercholesterolemia increases the oxidation of low density lipoprotein (LDL) which subsequently leads to atherogenesis. The oxidized LDL are also known to increase in vitro macrophage synthesis of glutathione. The purpose of this study was to investigate the relationship between lipid parameters and the glutathione system (glutathione, glutathione S-transferase) in total blood and within leukocytes. The glutathione and glutathione S-transferase were evaluated by spectrophotometric methods in sixty-two healthy volunteers (32 women, 30 men, mean age 39.9 +/- 7.7). No correlation was found between the level of blood cholesterol and the values of the blood glutathione system. However, a positive correlation between the values of glutathione and glutathione S-transferase in leukocytes and the blood cholesterol level was only found in women (r = 0.55 and r = 0.50 respectively, p < 0.01). We also found in men a positive correlation between body mass index and glutathione S-transferase in total blood and within leukocytes (r = 0.38, p < 0.05, r = 0.5, p < 0.01 respectively). No correlation was found between age, smoking and the values of the glutathione system. Our results suggest that the glutathione system in leukocytes is related to blood cholesterol levels. The fact that this positive correlation was only observed in women points to a possible role of estrogens in the regulation of the glutathione system which merits to be further studied.

Adult↗