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Biomedical subjects

S Burstein

Publications and source records attributed to S Burstein.

At least 73 records · Page 4Linked to original sources
PubMed1984

Prostaglandins and cannabis--XIII. Cannabinoid-induced elevation of lipoxygenase products in mouse peritoneal macrophages.

The phospholipases controlling the release of arachidonic acid in mouse peritoneal macrophages have been shown to be stimulated by the natural psychoactive cannabinoids. A close correlation was observed between the potencies of these substances in elevating arachidonate levels in vitro and the reported activities in a behavioral assay in monkeys and in producing a "high" in humans. The order of activity with the macrophages was delta 1-tetrahydrocannabinol (delta 1-THC) greater than 7-OH-delta 1-THC greater than 6 alpha-OH-delta 1-THC greater than 6 beta-delta 1-THC much greater than delta 6-THC-7-oic acid. It is suggested that this effect, which has now been shown in several diverse cell types, may serve as a model for studying the mechanism of action of THC.

Animals↗
PubMed1984

Rapid synthesis of 26-hydroxycholesterol from mevalonic acid in the Syrian hamster.

Using isotope-ratio mass spectrometry, newly synthesized 26-hydroxycholesterol and its derivative, 3 beta-hydroxy-5-cholenoic acid, were detected in the liver and bile of animals within 2 h following intravenous administration of [5-13C]mevalonic acid. The findings indicate that 26-hydroxycholesterol merits further consideration as an in vivo modulator of HMG-CoA reductase activity.

Animals↗
PubMed1984

Stimulation of sphingomyelin hydrolysis by cannabidiol in fibroblasts from a Niemann-Pick patient.

The hydrolysis of sphingomyelin in cells derived from a Niemann-Pick patient was studied using both a labelled precursor and measurement of endogenous levels. In vitro exposure of the cells to cannabidiol resulted in a large decrease in both the relative and absolute amounts of this lipid; the drug had a smaller effect on normal fibroblasts. Cannabidiol has been tested in the clinic as an antiepileptic agent with some success; our findings suggest that it may also be useful in relieving the symptoms associated with Niemann-Pick disease.

Cannabidiol↗
PubMed1984

Stimulation of prostaglandin synthesis in WI-38 human lung fibroblasts following inhibition of phospholipid acylation by p-hydroxymercuribenzoate.

The release of arachidonic acid and its metabolites, prostaglandin E2 and thromboxane A2, from WI-38 human lung fibroblasts was modulated by p-hydroxymercuribenzoate. Exposure to the inhibitor resulted in a dose-dependent decrease in [1-14C]arachidonic acid uptake and incorporation into phospholipids and neutral lipid pools. Activities of lung fibroblast arachidonyl-CoA synthetase and lysolecithin acyltransferase were inhibited by 100 microM p-hydroxymercuribenzoate. [14C]Arachidonic acid labelled fibroblasts exhibited an increased release of [14C]arachidonate and [14C]prostaglandin E2 of 54% and 112%, respectively, when exposed to 100 microM of inhibitor. The stimulatory effects of 8.0 microM delta 1-tetrahydrocannabinol on arachidonate release and prostaglandin E synthesis (Burstein, S., Hunter, S.A., Sedor, C. and Shulman, S. (1982) Biochem. Pharmacol. 31, 2361-2365) were modified by the inclusion of inhibiting agent, resulting in a 608% stimulation in arachidonic acid release, while prostaglandin E2 and thromboxane A2 synthesis increased 894% and 390%, respectively, over levels obtained by untreated cells. The levels of arachidonate metabolites were altered by inhibitor when compared to cells treated with cannabinoid alone. No significant inhibition by delta 1-tetrahydrocannabinol was found on arachidonic uptake in these cells. In unlabelled studies, p-hydroxymercuribenzoate resulted in a profound, dose-dependent stimulation of prostaglandin E synthesis of 1490% at 150 microM inhibitor concentration. These results provide evidence that free arachidonate is reincorporated via acylation, thereby implicating this pathway as a possible control mechanism for the synthesis of arachidonic acid metabolites.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1983

Leiomyosarcoma of the duodenum recognized preoperatively.

We report the preoperative histologic diagnosis of leiomyosarcoma of the duodenum and review the clinical aspects and treatment of this tumor. The endoscopic techniques were critical in obtaining the diagnosis and deciding the treatment plan.

Aged↗
PubMed1983

The induction of antibodies to human luteinizing hormone by contaminated clinical pituitary hormone preparations.

Three children with hypopituitarism had elevated LH levels measured by RIA which were incompatible with their stage of sexual maturation. Each of the children had been administered parenteral pituitary hormone preparations: one patient, human (h) GH for 3 2/1 yr; one patient, bovine TSH twice to evaluate thyroid responsiveness; and two patients, posterior pituitary extract by nasal insufflation for 7 5/12 ad 4 9/12 yr to treat diabetes insipidus. Each of these children had developed antibodies of the immunoglobulin G class which bound [125I]hLH in vitro in a displaceable fashion. In two of the patients, the antibody reacting with hLH was found after therapy with pituitary hormones of bovine or porcine origin and before treatment with hGH, while on child had received only hGH therapy. These antibodies interfered in the assay for hLH and were responsible for the spurious elevations of serum immunoreactive hLH. None of these children had undergone spontaneous puberty, including at least one who may not have been gonadotropin deficient. To reduce the risk of generating high potency neutralizing antibodies, only highly purified, monomeric pituitary hormone preparations or pure synthetic hormone preparations should be used for diagnosis and chronic replacement therapy.

Adolescent↗
PubMed1983

Effects of growth hormone replacement therapy on 1,25-dihydroxyvitamin D and calcium metabolism.

To elucidate the changes in mineral metabolism and blood concentrations of calciotropic hormones which accompany GH therapy, we studied 12 GH-deficient children for 5 days before and for 1 week after high dose (5 IU/day) GH therapy, and again at 1 month, 3 months, and 1 yr of replacement therapy (0.1 IU/kg to a maximum dose of 2 IU three times weekly). All responded with acceleration of height velocity, and bone ages advanced appropriately. Fasting serum ionized calcium levels did not change: 4.11 +/- 0.06 (SEM) mg/dl before, 4.19 +/- 0.05 for the week of high dose therapy, and 4.20 +/- 0.14 during replacement therapy. Likewise, fasting serum parthormone did not vary: 38.9 +/- 2.6 muleq/ml before to 44.1 +/- 9.2 at 1 yr. Twenty four-hour nephrogenous cyclic AMP (NcAMP) did not vary over the first week (1.2 +/- 0.7 nmol/dl glomerular filtrate before, 1.3 +/- 0.4 after 1 week), but increased to 5.3 +/- 1.9 after 1 yr (alpha less than 0.001). The response of ionized calcium and parathormone to a standardized disodium EDTA infusion of 50 mg/kg also did not change. The mean fasting serum calcitonin level was not different before therapy (29.4 +/- 2.8 pg/ml), after 1 week (21.5 +/- 1.8), or after 1 yr (42.4 +/- 11.0). However, the mean serum 1,25-dihydroxyvitamin D concentration rose from 33.1 +/- 3.3 pg/ml before therapy to 68.3 +/- 12.3 on the seventh day of high dose therapy (alpha less than 0.01), returning to pretherapy values by 1 month. We conclude that high dose GH therapy in GH-deficient children raises 1,25-dihydroxyvitamin D concentration acutely, but that long term, physiological replacement therapy does not cause such an effect. Because NcAMP excretion rose in the absence of an increase in serum parathormone concentration, we conclude that GH sensitizes the kidney to a cAMP-mediated effect of parathormone.

Adolescent↗
PubMed1983

The role of human growth hormone in the regulation of cholesterol and bile acid metabolism.

Cholesterol and bile acid metabolism was studied in 16 children with human GH (hGH) deficiency (11 with isolated hGH deficiency and 5 with multiple trophic hormone deficiency) before and after 6 months of hGH therapy. We measured plasma lipid concentrations, biliary lipid composition, and cholesterol saturation indices; calculated the bile acid pool size measured by the isotopic dilution technique using the stable isotope chenodeoxycholic-[11,12-d2] acid; and measured cholesterol and bile acid synthetic rates by sterol balance techniques. In all 16 patients, plasmas lipid concentrations were unchanged after hGH therapy; total plasma cholesterol was 182 +/- 10 (+/-SEM) mg/dl before and 179 +/- 9 mg/dl after treatment, high density lipoprotein-cholesterol was 47 +/- 2 mg/dl before and 49 +/- 3 mg/dl after treatment, low density lipoprotein-cholesterol was 112 +/- 10 mg/dl before and 111 +/- 8 mg/dl after therapy, and triglyceride was 113 +/- 13 mg/dl before and 107 +/- 10 mg/dl after hGH therapy. Biliary lipid composition and cholesterol saturation in 10 patients were similar to those in controls and unchanged with hGH therapy. Cholesterol synthesis (n = 14) was unchanged (7.6 +/- 1.4 vs. 9.6 +/- 1.2 mg/kg X day); however, bile acid synthesis (n = 15) increased from 3.1 +/- 0.4 to 4.3 +/- 0.6 mg/kg X day (P less than 0.025) after therapy. The chenodeoxycholate pool size (n = 8) was significantly reduced (P less than 0.025) before hGH treatment (416 +/- 64 mg/m2) compared to that in controls (617 +/- 45 mg/m2) and increased to 620 +/- 72 mg/m2 after hGH therapy (P less than 0.05). Chenodeoxycholate pool size expansion during hGH therapy was, at least in part, caused by an increase in hepatic bile acid synthesis. These findings suggest that hGH may indirectly modulate cholesterol metabolism through regulation of hepatic cholesterol 7 alpha-hydroxylase activity, the rate-limiting enzyme of bile acid synthesis.

Adolescent↗
PubMed1983

Hypergonadotropism in peripubertal boys with chronic renal failure.

Serum gonadotropin and testosterone concentrations were measured in ten peripubertal boys to assess the effects of uremia on pubertal maturation. Serum luteinizing hormone (LH) concentrations were elevated for stage of puberty in eight boys, whereas in most boys serum follicle-stimulating hormone and testosterone concentrations were normal. Serum LH concentrations correlated with the severity of uremia. LH levels declined when measured 1 year after the initial measurements in four boys who received renal allografts, but were further elevated in two boys who were treated conservatively. Elevated serum LH concentrations in the presence of normal serum testosterone concentrations imply limited testicular sensitivity to the effects of LH in these peripubertal boys, as has been documented for adult men with chronic renal failure. Alternatively, there may be accumulation of an immunoreactive LH molecule that lacks bioactivity. A testicular dysfunction may explain the pubertal delay experienced by some uremic adolescent boys.

Adolescent↗
PubMed1983

Prostaglandins and cannabis. XII. The effect of cannabinoid structure on the synthesis of prostaglandins by human lung fibroblasts.

Earlier findings indicated that several other cannabinoids in addition to delta 1-tetrahydro-cannabinol (THC) were able to stimulate the synthesis of prostaglandins in cell culture systems. The present study was initiated to delineate the structural requirements for this effect within the cannabinoid series. Among the primary cannabinoids, we found that the trend was for more planar structures to show greater activity. In the case of THC metabolites, the order of activity was delta 1-THC greater than 7-oxo-delta 1, 6-THC greater than 7-OH-delta 1-THC greater than 3"-OH-delta 1-THC = 6 beta-OH-delta 1-THC = 6 alpha-OH-delta 1-THC greater than delta 1, 6-THC-7-oic acid. The latter sequence compares favorably with the available data on the behavioral assay in the rhesus monkey and the subjective "high" in humans. We also observed a good correlation between the release of arachidonic acid and the production of prostaglandin E, over a series of eight cannabinoids. This gives further support that the site of action in this effect is the elevation of activity of the phospholipase(s) responsible for supplying precursor arachidonic acid for prostaglandin synthesis.

Arachidonic Acids↗
PubMed1982

Prostaglandins and cannabis--IX. Stimulation of prostaglandin E2 synthesis in human lung fibroblasts by delta 1-tetrahydrocannabinol.

Preliminary data [S. Burstein and S. A. Hunter, Biochem. Pharmac. 27, 1275 (1978)] showed that cannabinoids at levels of 1 microM or greater elevated the concentrations of prostaglandins in cell culture models. Further study [S. Burstein and S. A. Hunter, J. clin. Pharmac. 21, 240S (1981)] led to the suggestion that this effect was due to a stimulation of phospholipase A2 resulting in the release of free arachidonic acid which was then partly converted into the prostaglandin(s) normally synthesized by the particular target system. The present report gives detailed data on the cannabinoid-induced synthesis of prostaglandin E2 by te WI-38 fibroblast derived from human lung. The effect could be blocked by pretreatment with mepacrine, a phospholipase inhibitor, and aspirin, a cyclooxygenase inhibitor. These findings lend support to the hypothesis that some of the in vivo actions of the cannabinoids are due to modulations in prostaglandin synthesis at various tissue sites.

Arachidonic Acid↗
PubMed1982

Prostacyclin production by vein grafts in the arterial circulation: a study in rats.

The in vitro production of prostacyclin by vein grafts was measured using vascular rings followed by radioimmunoassay of the medium. The grafts were prepared by interposing a segment of epigastric vein in a gap in the ipsilateral femoral artery of the rat. Measurements made over a period of 1 to 42 days showed a progressive rise from venous levels (less than 0.2 ng/ml) to values close to the arterial controls (10.9 +/- 2.2 ng/ml). This deficiency of prostacyclin synthesis during the "arterialization" of the graft may account for some of the early failures which can occur in vein grafting and suggests the possibility of pharmacological intervention to improve the success rate.

Animals↗
PubMed1982

Hemoglobin A1 in hemolysates from healthy and insulin-dependent diabetic children, as determined with a temperature-controlled minicolumn assay.

We report age-specific glycohemoglobin values for nondiabetic infants, children, and young adults. These values were determined with an ion-exchange "mini-column" in a specially designed and constructed water bath that maintains column temperature at 23 +/- 0.1 degrees C. Two in-house-prepared controls with glycohemoglobin content amounting to 6.36% and 11.87% of total hemoglobin, stored at -20 degrees C, were used to assess long-term analytical precision. Between-day precision (CV) was 1.4% and 1.65%, respectively. We found a significant correlation (r = 0.981, p less than 0.01) between the glycohemoglobin value and the physicians' independent assessment of clinical control in 129 insulin-dependent diabetics, ages 3-23 years. There were significant differences (p less than 0.05) between glycohemoglobin values between patients with well-controlled or poorly controlled diabetes and those with intermediate control. Reported studies of 20 patients over three to 12 weeks showed that changes in clinical control were paralleled by changes in glycohemoglobin values.

Adolescent↗
PubMed1982

Cerebrotendinous xanthomatosis: reduced serum 26-hydroxycholesterol.

Serum 26-hydroxycholesterol was quantitated by isotope dilution-mass spectrometry in normal individuals and in patients with cerebrotendinous xanthomatosis. In the normal individuals, the concentration of 26-hydroxycholesterol in serum ranged from 4.3 to 13.0 microgram/100 ml. In five patients with CTX, 26-hydroxycholesterol in serum ranged from 0 to 0.6 microgram/100 ml. The findings can be explained by reduced or absent mitochondrial C27 steroid 26-hydroxylase activity. The method is useful for detection of CTX and perhaps other disturbances of sterol and bite acid metabolism.

Brain Diseases, Metabolic↗
PubMed1981

26-Hydroxycholesterol. Identification and quantitation in human serum.

Using isotope dilution mass spectrometry, 26-hydroxycholesterol was identified in the serum of normal adults. Total values ranged from 9.2 to 25.6 micrograms/100 ml of which 31-35% was free sterol. Density gradient ultracentrifugation indicates that the steroid is distributed among the low and high density lipoproteins.

Gas Chromatography-Mass Spectrometry↗
PubMed1981

Bile acid synthesis. Metabolism of 3 beta-hydroxy-5-cholenoic acid in the hamster.

Synthesis of 3 beta-hydroxy-5-[1,2-3H]cholenoic acid has permitted a study of its metabolism in bile-fistula hamsters that received the compound by intravenous infusion. Metabolites in bile were identified by reverse isotope dilution after their complete resolution by high pressure liquid chromatography using muPorasil. Recovery of administered radioactivity ranged from 21-60% in three animals. In each study, lithocholic acid (0.8-4.4%) and chenodeoxycholic acid (7.8-11.3%) were identified as metabolites of 3 beta-hydroxy-5-cholenoate and can be considered primary bile acids in the side-chain pathway of bile acid synthesis beginning with the oxidation of cholesterol to 26-hydroxycholesterol.

Animals↗