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Biomedical subjects

A Rubinstein

Publications and source records attributed to A Rubinstein.

At least 109 records · Page 6Linked to original sources
PubMed1994

Alkaline phosphatase band-10 fraction as a possible surrogate marker for human immunodeficiency virus type 1 infection in children.

We report the utility of a possible lymphocyte fraction of alkaline phosphatase (ALP band-10) activity in serum to predict human immunodeficiency virus type 1 (HIV-1) infection in children born to HIV-1-seropositive mothers. The presence of ALP band 10 in serum consistently correlated with HIV-1 infection status as judged by positive HIV-1 culture, two consecutive HIV-1 p24 antigen results greater than 30 pg/mL in serum, and the subsequent confirmation of seroconversion to HIV-1 antibody after clearance of maternal IgG anti-HIV-1 antibody ascertained between 15 to 24 months post partum. Infection with HIV-1 was correctly identified in 31 samples from 18 patients ranging in age between 0.1 to 10 years; the absence of similar infection was noted in 14 samples from nine patients who served as controls and whose serum samples did not exhibit ALP band-10 activity. This ability of serum ALP band-10 activity to predict HIV-1 infection status in children as young as 2 months may be useful as a surrogate marker for early identification of HIV-1 infection in infants born to HIV-1-seropositive women long before the clearance of maternal anti-HIV-1 antibodies can be ascertained.

Alkaline Phosphatase↗
PubMed1994

Continuous intravenous heparin administration in humans causes a decrease in serum lipolytic activity and accumulation of chylomicrons in circulation.

Heparin is a well-known, widely used anticoagulant drug. In addition to its anticoagulant properties, however, it also has a marked influence on fat metabolism. Postprandial lipoproteins may contribute significantly to the development of coronary heart disease. Therefore, it is important to evaluate the effects of heparin on these lipoproteins. The effect of continuous heparin administration on postprandial lipoprotein metabolism was studied in 11 patients with thromboembolic disease. Results were compared with those in a group of six patients given no heparin. Two vitamin A-fat loading tests were done: the first, 5 days before heparin was started and the second, on the fourth day of continuous heparin drip of 1000 U/h, maintaining PTT levels at twice the baseline. To study the effect of acute heparin, an additional fat loading test was done in five patients on the first day of heparin treatment. Vitamin A, specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). The concentrations of chylomicron (Sf > 1000)- and nonchylomicron (Sf < 100)-retinyl palmitate were measured for 10 h postprandially. Four days of continuous intravenous heparin administration increased the area below the chylomicron RP curve from 11091 +/- 4393 to 17684 +/- 5949 micrograms/l.h (P < 0.003). When measured on the first day of heparin treatment in five patients, the area of the chylomicron fraction was reduced from 16678 +/- 6895 to 10474 +/- 3893 micrograms/l.h (P < 0.05). Postheparin lipoprotein lipase activity was significantly lower on the fourth day of heparin, administration than before treatment: 1.8 +/- 1.1 vs. 4.1 +/- 1.3 mumol/FFA per ml per h, respectively (P < 0.0005). In the six control patients with thromboembolic disease in whom heparin therapy was not indicated, no changes in postprandial lipoprotein levels or in lipolytic activity during hospitalization were found. The study demonstrates that 4 days of heparin administration causes an accumulation of chylomicrons in the circulation, most probably as a result of a marked decrease in serum lipolytic activity.

Adult↗
PubMed1993

Gastrointestinal parameters that influence oral medications.

The successful functioning of oral medication depends primarily on how the gastrointestinal (Gl) tract processes drugs and drug delivery systems. Parameters such as regional pH, motility (and hence residence time), and brush border and colonic microflora enzymatic activity play an important role in the performance of orally administered dosage forms. In addition, medications are required to treat disease states that alter normal functions of the body. This review (which summarizes the symposium of the same title undertaken in the 2nd Jerusalem Conference on Pharmaceutical Sciences and Clinical Pharmacology, Jerusalem, Israel, May 1992) focuses on two aspects: (1) how some physiological parameters of the intestine can be manipulated to achieve control over drug absorption (P. Bass: alteration of the paracellular space of enterocytes with glucose to modulate the passive movement of drugs; E. Ziv: intestinal absorption of insulin) and spatial placement of drugs (D.R. Friend: use of colonic beta-glucosidases to target glycoside prodrugs of steroids to the large bowel; A. Rubinstein: specific degradation of polysaccharide matrices by colonic bacteria); and (2) how abnormalities of the Gl tract affect drug performance (J.B. Dressman: physiological and pathophysiological changes in upper Gl tract pH may lead to alterations in drug bioavailability; W. A. Ritschel: influence of diseases on the pharmacokinetics of drugs).

Administration, Oral↗
PubMed1993

Protection of the rat jejunal mucosa against oxidative injury by cationized superoxide dismutase.

The purpose of the present study was to investigate whether local prevention of luminal superoxide-mediated biological damage in the rat jejunal mucosa could be achieved by use of cationized superoxide dismutase (SOD). Mucosal damage was induced in a closed circulating intestinal loop of the rat either by a mixture of xanthine and xanthine oxidase or by a mixture of xanthine, xanthine oxidase, and chelated ferrous sulfate. Thus, superoxide radicals or hydroxyl (OH.) radicals were induced. The mucosal activity of intracellular lactate dehydrogenase and the levels of cellular potassium ions were used to quantitatively characterize the tissue damage. SOD was cationized by reaction with N,N'-dimethyl-1,3-propanediamine to yield a soluble product or with polyhistidine to yield an insoluble product. The cationization yield and the activity of the modified enzymes were assessed, and the ability of the cationized enzymes to protect the rat jejunal mucosa against oxidative stress was studied. It was found that cationized SOD provided significant protection against mucosal damage induced by OH. radicals. The findings indicate the potential role of cationized enzymes in the local protection of the intestinal epithelium against pathological processes associated with oxidative stress.

Animals↗
PubMed1993

Epidemiology of achalasia in central Israel. Rarity of esophageal cancer.

The epidemiology of achalasia was studied in a predominantly urban, Jewish population of approximately 1.3 million, in central Israel, during the years 1973-1983. One hundred sixty-two proven cases were collected, representing all known patients with achalasia in the study area. There were no gender differences. The majority of cases were diagnosed within two years of onset of symptoms, although the median delay in diagnosis was 4.4 +/- 5.3 years. The disease was rare in the first two decades of life. The prevalence (in 1983) in the first two decades was 0.7/10(5) rising to 36.2/10(5) above age 70. The mean annual incidence in the years 1973-1978 was 0.8/10(5). It rose slightly to a mean annual incidence of 1.1/10(5) in the years 1979-1983. The prevalence of the disease in 1973 and 1983 was 7.9/10(5) and 12.6/10(5), respectively. The age-adjusted prevalence in 1973 was higher in Asian and African born Jews as compared to those born in Europe, America, or Israel. This difference disappeared by the year 1983. No case of cancer of the esophagus was found among our patients. This may be due to the nonselected, regional nature of our series or to the effects of earlier therapy of achalasia in recent decades.

Adult↗
PubMed1993

Enzymatic cleavage of disaccharide side groups in insoluble synthetic polymers: a new method for specific delivery of drugs to the colon.

A series of water-insoluble acrylic polymers containing disaccharide side groups were synthesized and evaluated in vitro. A cellobiose-derived monomer, 4-O-beta-D-glucopyranosyl-1-methacrylamido-1-deoxy-D-glucitol, was prepared and copolymerized with methacrylic acid. Two different modes of polymerization were used to give two products, P-1 and P-2. A homopolymer, P-3, was also synthesized using the same method as P-2. The degradation of the disaccharide side groups in these polymers and the monomer was evaluated by incubation with beta-glucosidase and measurement of the amount of glucose cleaved. It was found that the degradation rate increased in those polymers possessing lower contents of the disaccharide side groups (i.e. higher content of methacrylic acid). Scanning electron microscopy (SEM) observations of cross-sectioned slabs of P-1 visualized the degradation of the polymer. The enzymatic reaction caused a porous structure to be formed. The increased porosity may be used for the specific release of drugs into organs that contain large amounts of beta-glucosidases, such as the human colon.

Carbohydrate Sequence↗
PubMed1993

A rapid test for the detection of human immunodeficiency virus antibodies in cord blood.

A commercially available rapid test (HIVCHEK) was compared with an enzyme-linked immunosorbent assay (ELISA) for identifying human immunodeficiency virus type 1 in the serum of newborn infants. Of 1309 cord blood samples tested, the HIVCHEK test detected all the true-positive samples detected by ELISA. Of the 35 samples with positive ELISA results, six had negative results on Western blot; only 1 of the 30 samples with positive HIVCHEK results had negative results on Western blot. Thus the HIVCHEK test can be used to facilitate the rapid identification of HIV-1 in the serum of newborn infants.

Colorimetry↗
PubMed1993

In vitro evaluation of calcium pectinate: a potential colon-specific drug delivery carrier.

Calcium pectinate (CaP)--the insoluble salt of pectin--can potentially be used as a colon-specific drug delivery system. The use of CaP as a carrier was based on the assumption that, like pectin, it can be decomposed by specific pectinolytic enzymes in the colon but that it retains its integrity in the physiological environment of the small bowel. The biodegradation of the carrier was characterized by monitoring the percent cumulative release of the insoluble drug indomethacin, incorporated into pectin or CaP matrices. Compressed tablets of pectin and indomethacin were analyzed for degradation in the presence of Pectinex 3XL, a typical pectinolytic enzyme mixture, and in the presence of the human colonic bacterium Bacteroides ovatus. The degradation of CaP-indomethacin tablets was assessed in the presence of Pectinex 3XL and in rat cecal contents. The release of indomethacin was significantly increased (end-time percentage cumulative release vs control) in the presence of Pectinex 3XL (89 +/- 20 vs 16 +/- 2 for CaP tablets), Bacteroides ovatus (12 and 22 vs 5.2 for pectin tablets), and rat cecal contents (61 +/- 16 vs 4.9 +/- 1.1 for CaP tablets). The weight loss of tablet mass was significantly higher (end-time dry weight vs control) in the presence of Pectinex 3XL (0 vs 75 +/- 6% of initial weight for CaP tablets). These findings indicate the potential of CaP, compressed into tablets with insoluble drug, to serve as a specific drug delivery system to the colon.

Animals↗
PubMed1993

Prevention of oxidative damage in the rat jejunal mucosa by pectin.

The role of the soluble non-starch polysaccharide pectin in the prevention of oxidative damage induced by peroxy, superoxide and hydroxyl radicals to the rat jejunal mucosa was studied. The oxidative stress was introduced to the rat jejunal mucosa by means of a closed-loop perfusion system and was characterized biochemically by monitoring the enterocyte activity of the enzyme lactate dehydrogenase (EC 1.1.1.27) and the K+ level. Aqueous solutions of pectin were perfused into the rat jejunum before the oxidative stress inducers. The possible protection effect was evaluated by comparing the mucosal integrity (as measured by biochemical variables) to the values obtained after perfusion with the oxidative stress inducers only. We found that: (a) mucosal damage was detected following the perfusion of peroxy and hydroxyl radicals in the rat jejunum, but not following perfusion of the superoxide radical; (b) a significant reduction in the mucosal damage was noted when pectin was perfused before the perfusion with the peroxy radical induction; (c) full protection against the mucosal damage induced by hydroxyl radicals was achieved when pectin was perfused before the damage induction.

Animals↗
PubMed1993

The Gulf War and diabetes mellitus.

The Gulf war was a traumatic and stressful event for the inhabitants of Tel-Aviv and vicinity. The entire population changed its way-of-life. In order to evaluate the influence of the war stress on glucose control, we reviewed the charts of all diabetic patients attending the outpatient clinics at the Tel-Aviv Medical Centre, whose weight and glycated haemoglobin was determined between 15.1.91 and 2.5.91 (the war period), with comparative measurements within 4 1/2 months both before and after these dates. Sixty-six patients with non-insulin dependent diabetes mellitus (NIDDM) and 16 with insulin-dependent diabetes mellitus (IDDM) were examined. During the war, their glycated haemoglobin increased by 10.1 to 10.9% and from 9.6 to 10.2%, respectively. Weight increased from 76.1 to 77.5 kg in the NIDDM and from 63.2 to 64.7 kg in the IDDM patients. Both measurements returned to baseline after the war. No correlation was found between the changes in glycated haemoglobin and weight.

Adult↗
PubMed1993

Maternofetal transmission of human immunodeficiency virus-1: the role of antibodies to the V3 primary neutralizing domain.

The increase in the number of human immunodeficiency virus-1 (HIV-1)-infected children is a direct consequence of the heterosexual spread of the disease to women and the growing number of HIV-positive i.v. drug users. It is not known how the majority of infants born to HIV-1-infected women escape HIV-1 infection, and, for those infected, the timing of HIV-1 transmission has yet to be determined. In addition, the role of maternal antibodies in the prevention of HIV-1 transmission to the fetus is unclear. We have previously demonstrated a correlation between vertical transmission and the absence of high-affinity/avidity antibodies to a peptide, KRI-HIGPGRAFYT, which corresponds to a region of the primary neutralizing domain of the gp120 V3 loop of HIVMN (MN-PND). The present study examines the correlation between the presence of these high affinity antibodies in women completing a pregnancy or undergoing an elective abortion and the detection of HIV-1 infection in their aborted fetuses. In several instances, transmission occurred despite high-affinity antibodies to the MN-PND. We have, therefore, evaluated the reactivity of sera to different MN-PND variants. In one infant born to a mother with high-affinity/avidity antibodies to KRI-HIGPGRAFYT (classic MN-PND), the infected baby developed antibodies to an MN-PND variant peptide against which his mother did not mount a humoral immune response during pregnancy. This finding indicates that fetal infection with MN-PND escape mutants arising during pregnancy may occur during a period when the mother is serologically negative.

Amino Acid Sequence↗
PubMed1993

Efficacy and safety of pravastatin once daily in primary moderate hypercholesterolemia: the Israeli experience.

Seventy-seven hypercholesterolemic patients participated in a 26-week, multicenter, randomized, double-blind, placebo-controlled study that investigated the efficacy and safety of pravastatin therapy. All patients had primary moderate hypercholesterolemia (total cholesterol 200-300 mg/dl, at the end of a 6-week dietary run-in period) and two additional coronary risk factors. Pravastatin, 20-40 mg/day given at bedtime, reduced total cholesterol by 19-22%, LDL-cholesterol by 24-30%, triglycerides by 10-30% and increased HDL-cholesterol by 9-13%. The drug caused mild elevation in alanine aminotransferase and aspartate aminotransferase. Almost all these elevations were within normal limits and no patient was clinically symptomatic. No other significant differences were observed between the pravastatin and the placebo-treated groups with regard to other adverse effects and to patient compliance and withdrawal. It is concluded that pravastatin has a beneficial effect on the lipid profile and that the drug is safe and well tolerated.

Adult↗
PubMed1992

The role of cationized catalase and cationized glucose oxidase in mucosal oxidative damage induced in the rat jejunum.

The successful prevention of hydrogen peroxide-induced damage to the rat jejunal mucosa by cationized catalase is described in this study. Biological damage was induced in a closed circulating intestinal loop of the rat by hydrogen peroxide and by hydroxyl radicals induced in situ via the metal-mediated Haber-Wiess reaction. The mucosal activity of lactate dehydrogenase and the amount of potassium ions were used to quantitatively characterize the tissue damage. Catalase was cationized by reacting it with N,N'-dimethyl-1,3-propanediamine to give a soluble product or with polyhistidine to give an insoluble product. The activity of the modified enzymes was assessed, and their ability to protect the rat jejunal mucosa against oxidative stress was studied. It was found that in all cases the cationized enzymes were superior to the native catalase in their shield capability. A significant protection against Fe(II)/H2O2 and ascorbic acid/copper ion-mediated damage was obtained when the cationized enzymes were used. In the presence of glucose, native glucose oxidase failed to cause damage in the rat jejunal mucosa; however, the cationized enzyme caused profound tissue injury. These findings indicate the potential therapeutic merit of cationized enzymes for the treatment of pathological processes in the intestine, whenever oxidative stress is involved.

Animals↗