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Biomedical subjects

R Anton

Publications and source records attributed to R Anton.

At least 37 records · Page 2Linked to original sources

Endoscopic procedures for resection of arteriovenous malformations.

BACKGROUND: Resection of arteriovenous malformations (AVMs), particularly those located in functional areas, requires precision. To enhance that precision, endoscope-assisted microsurgery has been employed at Loma Linda University. METHODS: Twenty-five consecutive cases of AVM were treated microsurgically with endoscopic assistance. Patients were divided into two groups: (1) those having AVMs in functional areas, and (2) those whose AVMs extended into the ventricle, either in the trigonal area or the capsulocaudatothalamic area. The endoscope was inserted into the subarachnoid space to interrupt communicating venules around the major draining vein and into the cleavage developed between the AVM venous loops and surrounding brain tissue as shunting arterioles and communicating venules were interrupted. For surgery of intraventricular AVMs, the curved endoscope was inserted into the ventricle, providing visualization of the AVM core, which was dissected from the ventricular side. RESULTS: AVMs were totally resected in all cases except for two patients with capsulocaudatothalamic AVMs, which were decreased in size sufficiently to receive radiosurgery. CONCLUSION: Endoscope-assisted microsurgery enhances magnification, illumination, and technical precision while the surgeon is dissecting the AVM core vessels and while operating on AVMs extending into the ventricle.

Adult↗

Dural closure with nonpenetrating clips prevents meningoneural adhesions: an experimental study in dogs.

OBJECTIVE: Meningospinal and cranial dural adhesions were compared in a canine model, after duraplasty using nonpenetrating clips or penetrating needles and sutures. METHODS: Fourteen dogs underwent bilateral craniotomies and duraplasties, with implantation of dural prostheses (DuraGuard; Biovascular Corp., Minneapolis, MN), using either 6-0 silk sutures or titanium clips (DuraClose; Surgical Dynamics, Norwalk, CT). Fourteen other dogs underwent L3-L4 laminectomies; three longitudinal dural incisions were closed with 6-0 silk sutures, 6-0 polyglactin 910 (Vicryl) sutures, or clips. Groups of eight dogs (four cranially treated and four spinally treated) were killed 6, 12, 24, and 52 weeks after surgery, and specimens were collected for study after perfusion and fixation (two cranial and two spinal dural reconstructions at 52 wk). Evaluations included assessment of the appearance of approximated dural margins and responses to clips, sutures, and dural prostheses (inflammation, foreign body reaction, fibrosis, and severity of meningospinal/meningocerebral adhesions). Data were evaluated using the Wilcoxon signed-rank and McNemar tests. RESULTS: Duraplasties with clips displayed significantly less extensive acute and chronic inflammation, foreign body reaction, and meningoneural adhesions than did repairs with needles and sutures. CONCLUSION: This report is the first long-term experimental study comparing two fundamentally different methods for dural repair in a relevant animal model.

Animals↗

Contribution of carbohydrate deficient transferrin to gamma glutamyl transpeptidase in evaluating progress of patients in treatment for alcoholism.

Eight previous investigations have suggested that conjoint consideration of findings on tests for gamma glutamyl transpeptidase (GGT) and carbohydrate deficient transferrin (CDT) substantially enhances sensitivity of screening for alcohol problems while minimally diminishing specificity. Using results from a large clinical trial, the current study evaluated the two tests singly and in combination as measures of three clinically important treatment outcome criteria: any drinking, at least one day of heavy drinking, and at least three consecutive days of heavy drinking during the past month. When scored by quartile, CDT is slightly better at screening for alcohol problems in males than GGT. However, CDT seems less accurate in females than GGT. Use of the two tests in consort moderately improves the individual test accuracy in predicting drinking status for both genders.

Adult↗

Natural dietary polyphenolic compounds cause endothelium-dependent vasorelaxation in rat thoracic aorta.

This study investigated the possible active principles which support the endothelial nitric oxide-dependent relaxation produced by red wine and other plant polyphenolic compounds in thoracic aorta from male Wistar rats (12-14 wk old). Relaxation experiments were recorded isometrically on vessels precontracted with norepinephrine. Ten different chromatographic fractions (3-18 mg) isolated from red wine polyphenolic compounds (RWPC) and some available defined polyphenols (10-15 mg) were tested. Fractions enriched into either anthocyanins or oligomeric condensed tannins exhibited endothelium-dependent vasorelaxant activity (maximal relaxation in the range of 59-77%) comparable to the original RWPC. However, polymeric condensed tannins elicited a weaker vasorelaxant activity than the original RWPC (maximal relaxation ranged between 20-47%, P < 0.01). Moreover, the representative of either phenolic acid derivatives (benzoic acid, vanillic acid, gallic acid), hydroxycinnamic acid (p-coumaric acid, caffeic acid) or the flavanol [(+)-epicatechin] classes failed to induce this type of response. Among the anthocyanins, delphinidin (maximal relaxation being 89%), but not malvidin or cyanidin, showed endothelium-dependent vasorelaxation. These results show that anthocyanins and oligomeric-condensed tannins exhibited a pharmacological profile comparable to the original RWPC. These compounds may be involved in the reduction of cardiovascular mortality related to the presence of wine, fruits and vegetables in the diet.

Animals↗

Modulation of cytotoxicity and enhancement of cytokine release induced by Viscum album L. extracts or mistletoe lectins.

Cytotoxic effects of Viscum album L. (mistletoe) extracts and mistletoe lectins were studied by light and electron microscopy. The first events observed were membrane perforation and protrusions typical for apoptosis. Inhibition of Molt 4 cell growth was obtained with lectin concentrations in the pg/ml range as long as cells were cultured in serum-free medium. Under this condition, mistletoe lectin-III was about 10 times more cytotoxic than mistletoe lectin-I; mistletoe lectin-II was in between. Lectin cytotoxicity was modulated by human serum from donors who had never been treated with mistletoe preparations and lectin-specific carbohydrates, added at the mmol/l range, particularly D-galactose (or beta-lactose) for mistletoe lectin-I and N-acetyl-galactosamine for mistletoe lectin-II and -III. In addition, at subtoxic concentrations, mistletoe lectin-I, -II and -III enhanced the production of cytokines (tumour necrosis factor-alpha, interleukin-1 alpha) by isolated human monocytes. The experimental results are discussed in relation to the treatment of cancer patients administered with mistletoe extracts.

Antibodies↗

Mistletoe lectins I, II and III induce the production of cytokines by cultured human monocytes.

The three mistletoe (Viscum album L.) lectins. ML I, ML II and ML III, were tested on their ability to enhance the secretion of the cytokines tumor necrosis factor (TNF)alpha, interleukin (IL)-1 alpha, IL-1 beta and IL-6 by human monocytes obtained from healthy donors. At lectin concentrations from 0.02 to 20/pg ml (100-10,000-fold lower than those showing toxic effects), stimulations of cytokine production several-fold over control values were observed. The immunoactivating concentrations by the three lectins were found different for each donor. At toxic concentrations, the amounts of IL-1 alpha, IL-1 beta and to a less extent of TNF alpha in monocytes supernatants were particularly high. The data are discussed in relationship with the cytotoxic and immunoactivating effects of mistletoe lectins and their interest in cancer treatment.

Cells, Cultured↗

Induction of cytochrome P4501A1 and P4504A1 activities and peroxisomal proliferation by fumonisin B1.

The effects of repeated exposure to fumonisin B1 (FB1) on hepatic and renal mixed function oxidase activities and peroxisomal proliferation has been examined in rats following intraperitoneal administration at three dose levels (0.125, 0.25, and 2.5 mg/kg) once a day for 6 days. At the two highest doses, FB1 increased the renal and hepatic N-demethylation of erythromycin (CYP3A1) and the hepatic O-deethylation of ethoxyresorufin (CYP1A1). FB1, at the highest dose of 2.5 mg/kg, also increased the renal O-deethylation of ethoxyresorufin. The liver, but not the kidney, was also susceptible to FB1-dependent induction of the 12- and 11-hydroxylation of lauric acid, suggesting induction of the CYP4A subfamily. Immunoblot studies employing solubilized microsomes from FB1-treated rats revealed that FB1, at the two highest doses, increased the apoprotein levels of CYP1A1 and CYP4A1. The same treatment with FB1 increased the beta-oxidation of palmitoyl-coenzyme A (CoA) in liver homogenates, and immunoblot analysis showed an increase in the apoprotein levels of the trans-2-enoyl-CoA hydratase trifunctional protein. The possible implications of these findings to the hepatocarcinogenicity of this mycotoxin are discussed.

Animals↗

Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH) and diazepam-binding inhibitor (DBI) during alcohol withdrawal and abstinence.

The neuropeptides diazepam binding inhibitor (DBI) and corticotropin-releasing hormone (CRH) elicit anxietylike symptoms when administered intracerebroventricularly to laboratory animals. Because of the similarities between the symptoms of certain anxiety states and the alcohol withdrawal syndrome, we hypothesized that increased secretion of either of these endogenous neuropeptides may, at least in part, be responsible for the symptoms of alcohol withdrawal. We therefore measured DBI and CRH concentrations in cerebrospinal fluid (CSF) of 15 alcohol-dependent patients during acute withdrawal (Day 1) and again at 3 week's abstinence (Day 21). In addition, plasma concentrations of cortisol were measured to evaluate the relationship between pituitary-adrenal axis activation and CSF CRH concentrations. CSF CRH (p < .04), but not CSF DBI, was significantly higher on Day 1 than on Day 21. Although there was a significant decrease in plasma cortisol from Day 1 to Day 21 (p < .001), a significant correlation between CSF CRH and plasma cortisol concentrations was not observed at either time point. Neither CSF neuropeptide correlated with clinical measures of withdrawal severity. These tentative findings may implicate CRH, but not DBI, in the pathogenesis of alcohol withdrawal. Alternately, the central release of CRH and DBI may not be adequately reflected in lumbar CSF.

Adult↗

Flavonoids extracted from fonio millet (Digitaria exilis) reveal potent antithyroid properties.

Digitaria exilis (fonio) is a tiny variety of millet commonly eaten by inhabitants of semiarid regions. A sample of fonio collected right in the middle of a severely iodine-depleted goitrous endemic was submitted to phytochemical investigations in order to assess the potential contributory roles played by vegetable molecules to the goitrogenic processes. The total content of flavonoids amounts to 500 mg/kg of the edible whole cereal grains. Their extraction and identification fail to detect the C-glycosylflavones described in other millet varieties but point out the presence of apigenin (A = 150 mg/kg) and of luteolin (L1 = 350 mg/kg). Ten percent of A and 80% of L1 are present in free form, whereas the remaining 90% of A and 20% of L1 are bound as O-glycosylflavones. Both A and L1 aglycones manifest strong anti-thyroid peroxidase (TPO) activities, resulting in a significant reduction of the hormonogenic capacity of this enzyme. In addition, L1 significantly depresses the cyclic AMP phosphodiesterase, implying a concomitant overproduction of the thyrotropin-dependent nucleotide. These last unreported data are regarded as counteracting to some extent the TPO-mediated goitrogenic properties of L1. Since fonio is devoid of other molecules likely to interfere with the thyroid function, our results are directly and casually attributed to A and L1 found in the customary diet.

1-Methyl-3-isobutylxanthine↗

Structure elucidation of three triterpene glycosides from the trunk of Argania spinosa.

The structures of three novel saponins from Argania spinosa, named arganines G, H, and J, have been elucidated by MS and NMR techniques as 3-O-beta-D-apiofuranosyl- (1-->4)-beta-D-glucopyranosyl-28-O-beta-D-glucopyranosylbayogenin (1), 3-O-beta-D-apiofuranosyl-(1-->4)-beta-D-glucopyranosyl-28-O-alpha- L- arabinopyranosylbayogenin (2), and 3-O-beta-D-apiofuranosyl-(1-->4)-beta-D-glucopyranosyl-28-O- [beta-D-apiofuranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L - rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl]bayogenin (3), respectively.

Carbohydrate Sequence↗

Prostaglandin H-synthase-2 is the main enzyme involved in the biosynthesis of octadecanoids from linoleic acid in human dermal fibroblasts stimulated with interleukin-1beta.

This study was focused on the characterization of the metabolism of linoleic acid by human dermal fibroblasts and the effect of interleukin-1 on the biosynthesis of octadecanoids. Dermal fibroblasts untreated and treated with recombinant IL-1beta were incubated with exogenous labeled linoleic acid. A combination of high performance liquid chromatography and gas chromatography-mass spectrometry was used as the analytic technique. We found that dermal fibroblasts convert linoleic acid mainly into 13-hydroxy-9-cis,11-trans-octadecadienoic acid (13-HODE) and 9-hydroxy-10-trans,12-cis-octadecadienoic acid (9-HODE), 13(S)-HODE and 9(R)-HODE being the predominant enantiomers. IL-1beta increased the formation of both 13-HODE and 9-HODE in a concentration-dependent manner with similar EC50 values as for prostanoid formation. This effect of IL-1beta on HODEs formation was concomitant with the expression of prostaglandin H-synthase-2. Formation of octadecanoids was inhibited in a concentration-dependent manner by acetylsalicylic acid and indomethacin. Dexamethasone, actinomycin D, and cycloheximide abolished the effect of IL-1beta on HODEs biosynthesis. Octadecanoid biosynthetic activity was associated with the microsomal fraction. Dermal fibroblasts incorporated [14C]-9-HODE and [14C]-13-HODE into phospholipids, mainly into phosphatidylcholine. IL-1beta increased significantly the esterification of 13-HODE in all glycerophospholipids, the major increase being observed in phosphatidylinositol. These results indicate that prostaglandin H-synthase-2 is the enzyme responsible for the increase in the ability to form HODEs of dermal fibroblasts stimulated with IL-1beta.

Cells, Cultured↗

Expression of bcl-2 inhibits necrotic neural cell death.

Cell death has been described as either apoptotic, in which the cell actively participates, or necrotic, in which the cell is felt to be passive. The proto-oncogene bcl-2 has been shown to inhibit apoptosis in some hematopoietic and neural cells, by an unknown mechanism. We demonstrate that bcl-2 inhibits the necrosis of neural cells induced by glutathione depletion. This finding demonstrates that bcl-2 does not inhibit the cellular death program directly; rather, bcl-2 modulates a cellular process that leads to apoptosis under some conditions but necrosis under others.

Animals↗

Triterpenoid saponins from the root of Sideroxylon foetidissimum.

Two novel triterpenoid saponins named sideroxyloside B and sideroxyloside C were isolated from the root of Sideroxylon foetidissimum. On the basis of spectroscopic and chemical methods, their structures were established as 3-O-beta-D-glucopyranosyl-28-O([beta-D-apiofuranosyl-(1-->3)-beta- D- xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->4)] [beta-D-apiofuranosyl(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-alph a-L- arabinopyranosyl) protobassic acid and 28-O([beta-D-xylopyranosyl-(1-->4)- alpha-L-rhamnopyranosyl-(1-->4)] [beta-D-apiofuranosyl-(1-->3)]-alpha-L- rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl) protobassic acid, respectively.

Carbohydrate Conformation↗

Triterpenoid saponins from Mimosa pigra.

Two novel triterpene glycosides have been isolated from Mimosa pigra. The aglycone of these two compounds was identified as machaerinic acid by 1H- and 13C-nmr spectroscopy and by comparison with an authentic sample. This aglycone is substituted at position C-3 by an identical oligosaccharide chain in these glycosides, and at position C-21 by either a Z/E-methoxycinnamic [1] unit or an E-cinnamic acid [2] unit.

Carbohydrate Sequence↗

Cytotoxic activity of Amaryllidaceae alkaloids.

25 Amaryllidaceae alkaloids belonging to different skeletal types were evaluated for their cytotoxic activity against one murine non-tumoral cell line (LMTK) and two human tumoral cell lines (Molt4 and HepG2) according to established protocols. Significant differences of activity related with the type of skeleton of the tested alkaloids could be observed. Pretazettine (22) was among the most active compound among the 25 tested alkaloids on the Molt4 lymphoid cells, but was inactive against HepG2 hepatoma. On the other hand, lycorenine (11) was found to be the most cytotoxic compound against HepG2 hepatoma, even though it appears to be active against Molt4 cells. Almost all of the tested alkaloids showed cytotoxic activity against fibroblastic LMTK cells. Only mesembrenone (25) showed some specificity against Molt4 cells in comparison to LMTK cells.

Alkaloids↗

Carbohydrate-deficient transferrin and false-positive results for alcohol abuse in primary biliary cirrhosis: differential diagnosis by detection of mitochondrial autoantibodies.

Primary biliary cirrhosis (PBC) is one of the few nonalcohol-induced liver pathologies that causes false positives in assays of carbohydrate-deficient transferrin (CDT) for diagnosing alcohol abuse. CDT was quantified by isoelectric focusing-immunoblotting-laser densitometry (IEF-IB-LD) analysis of serum from 117 women: 57 PBC patients, 20 alcohol abusers, and 40 healthy donors. Only 5% (3 of 57) of PBC patients were positive at the densitometric cutoff value chosen (> 90% specificity). Serum samples from 15 PBC patients were further evaluated by IEF-IB-LD and CDTect chromatography-RIA. Receiver-operating characteristic (ROC) analysis showed that IEF-IB-LD better discriminated between PBC and alcohol abuse than CDTect did. By ROC analysis, mitochondrial autoantibodies to pyruvate dehydrogenase antigen M2 detected by enzyme immunoassay yielded optimal test performance for diagnosing PBC. Of six patients falsely positive for CDT by CDTect, five (83%) tested M2-positive. Thus, abnormal CDT results should be further evaluated by mitochondrial antibody testing in patients with findings compatible with PBC.

Alcoholism↗