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Biomedical subjects

M J Berg

Publications and source records attributed to M J Berg.

At least 19 recordsLinked to original sources
PubMed1992

Surface characterization of activated charcoal by X-ray photoelectron spectroscopy (XPS): correlation with phenobarbital adsorption data.

X-ray photoelectron spectroscopy (XPS) was used to identify the functional states of carbon existing on the surfaces of various activated charcoals. The relative percentages of carbon, oxygen, and detectable trace elements comprising the activated charcoal surfaces were determined. Analysis of the carbon core-electron binding energy region revealed the existence of one hydrocarbon state (C-H, C-C are indistinguishable) and three oxygen-containing functional states. These states were hydroxyls or ethers (C-O), carbonyls (C = O), and carboxylic acids or esters (O-C = O). The C-O functional state contributed approximately 60-70% to the total percentage of oxygen-containing states. A very good correlation existed between the apparent areas occupied on the adsorbent surface per phenobarbital molecule and the relative percentages of the C-O functional state. Previously reported heat of displacement results for phenobarbital adsorption are now explained since the C-O state appears to be the primary site involved in the binding of phenobarbital by the activated charcoals.

Adsorption↗
PubMed1992

Parkinsonism treatment: Part III--Update.

OBJECTIVE: The purpose of this review is to update clinicians with recent advances in the management of parkinsonism, including drug therapy, transplantation, and diet. DATA SOURCES: Pertinent articles were obtained from an English-language literature search using MEDLINE (1970-1991), Index Medicus (1987-1991), Current Contents (1990), and bibliographic reviews of review articles. Index terms included parkinsonism, selegiline, pergolide, vitamin E, and transplantation. Fifty-five articles (representing 85 percent of the complete literature search) were selected by multiple reviewers for their contribution to the stated purpose. Emphasis was placed on double-blind, placebo-controlled, and randomized studies. Data from cited articles were examined by multiple reviewers for support of their stated hypothesis and were included as background for justification of major points in this article; critical studies were abstracted in more detail. RESULTS: New therapeutic measures have been added to the treatment of parkinsonism. Selegiline, a monoamine oxidase inhibitor type B, has shown beneficial results, especially in early stages. Pergolide, a dopamine agonist, may be an efficacious alternative to bromocriptine resistance or intolerable adverse effects. Vitamin E may have protective antioxidant properties, but very few clinical data are available. Fetal tissue transplantation needs continued research and remains very controversial. Diet modification may maximize the results of therapy with exogenous dopamine therapy. CONCLUSIONS: Clinicians should familiarize themselves with new alternatives for the management of parkinsonism in order to be reliable consultants for both professional and lay persons.

Antioxidants↗
PubMed1991

Brain cysteine proteinase inhibitors II: evidence that a 21-kDa papain-binding component resembles ras p21.

A 21-kDa protein extracted from rat or bovine brain at high pH was purified on alkylated-papain and shown to have dual ras-like and cysteine proteinase inhibitory (CPI) properties. This was demonstrated by its GTP-binding activity, cross-reactivity toward pan-reactive ras p21 monoclonal antibody, and inhibition of papain. The material eluted earlier than cystatins or kininogens on the alkylated papain-affinity column and was devoid of other CPIs based on immunoblot analysis. In a second procedure, ras p21s isolated from rat or bovine brain membranes by cholate extraction and purified by gel-permeation and hydrophobic interaction were shown to act also as potent CPIs, inhibiting rat brain cathepsin L, papain, or rat brain cathepsin B with Ki values of 3, 11, and 167 nM, respectively. This component cross-reacted with the monospecific anti-ras, but not with other anti-CPIs, and represented 3-4% of total GTP binding present in homogenates. The specific activity of the purified 21 kDa component was 4.7 nmol GTP-gamma-S bound per mg protein. The data support the notion that brain ras p21s constitute a separate group of CPIs and are available for regulating some aspects of brain protein turnover.

Amino Acid Sequence↗
PubMed1991

Model selection for the adsorption of phenobarbital by activated charcoal.

Activated charcoal is known to adsorb a wide variety of substances from solution, and several equations have been used to fit the resulting adsorption data. The determination of the correct model to fit phenobarbital adsorption onto activated charcoal was made using a calorimetric method. The differential heats of displacement of water by phenobarbital for four activated charcoals were determined and found to be linearly related to the amount of phenobarbital adsorbed. The activated charcoals studied had statistically similar heats of displacement. The linear relationship between heat evolved and the amount of phenobarbital adsorbed is consistent with the assumptions implicit in the Langmuir model.

Adsorption↗
PubMed1991

Differences in phenytoin biotransformation and susceptibility to congenital malformations: a review.

The clinical variability of teratogenic response to fetal drug exposure has been well documented. Metabolic differences in biotransformation have been shown to extend to multiple drugs and may involve many steps in drug metabolism with alterations of key intermediates. Although metabolic differences have been reported to be associated with complications of medication use, it has only recently been appreciated that such differences also may be associated in the unborn with the potential for the disruption of normal embryologic development and the production of congenital malformations. It has long been suspected that the teratogenicity of phenytoin may be mediated not only by the parent compound, but also by toxic intermediary metabolites that are produced during the biotransformation of the parent compound. Recent work elucidating differences in isoenzyme forms of cytochrome P-450 enzyme systems, glutathione, and microsomal epoxide hydrolase has provided increased interest in the multiple individual pharmacogenetic differences that may be significant factors affecting increased susceptibility to birth defects in individuals and families with fetal exposure to phenytoin.

Abnormalities, Drug-Induced↗
PubMed1988

Diversity of rat brain cysteine proteinase inhibitors: isolation of low-molecular-weight cystatins and a higher-molecular weight T-kininogen-like glycoprotein.

Conditions for extraction of rat brain soluble and particulate cysteine proteinase inhibitors (CPIs) were compared and an optimal one was selected to isolate low- and high-molecular-weight forms active toward papain or brain cathepsins B/L. The different forms were purified by affinity chromatography on alkylated papain, and identified on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels by use of Schiff's reagent, or by immunoblots using antisera to monomer or polymeric forms of human urinary cystatin c, to a human plasma histidine-rich glycoprotein (HRG), or to rat plasma T-kininogen. In particulates containing nuclei (P1) or synaptosomes (P2) the predominant CPI was an 80-kDa glycoprotein cross-reacting to anti-HRG and shown to be a T-kininogen by treatment with TPCK-trypsin, and subsequent bioassay of the released kinins. The levels found in rat brain were approximately 0.5 nmol/g wet weight. The higher-molecular-weight CPI potently inhibited cathepsin L hydrolysis of Leu-enkephalin at the Gly2-Gly3 bond with a Ki 10(-10) M. In contrast the low-molecular-weight CPIs were present in postmicrosomal fractions (S3) and cross-reacted with anti-cystatin c, but not with anti-HRG, anti-lysozyme, anti-beta protein amyloid peptide, or anti-T-kininogen. The low-molecular-weight forms were present at approximately 1-1.5 nmol/g wet weight and resembled "cerebrocystatin" purified previously from rat brain cytosol by M. Kopitar, F. Stern, and N. Marks [1983) Biochem. Biophys. Res. Commun. 112, 1000-1006.).

Animals↗
PubMed1988

Phenobarbital adsorption from simulated intestinal fluid, U.S.P., and simulated gastric fluid, U.S.P., by two activated charcoals.

Adsorption of phenobarbital from simulated intestinal and gastric fluids by two activated charcoals was studied. Adsorption isotherm data were analyzed by the linearized Langmuir equation and by nonlinear least-squares regression employing both Langmuir and Freundlich models. These analyses indicated differences in the capacities of the two charcoals for phenobarbital which could not be completely explained by surface-area considerations.

Adsorption↗
PubMed1987

Rat brain cathepsin L: characterization and differentiation from cathepsin B utilizing opioid peptides.

The specificity of purified rat brain cathepsin L (EC 3.4.22.15) was mapped by the use of synthetic and opioid peptides and some properties were compared to rat brain cathepsin B, rat kidney cathepsin L, and bovine spleen cathepsin C. Brain and kidney cathepsin L cleaved leucine or methionine enkephalin (LE or ME) at the Gly-Gly bond to release Tyr-Gly and Gly-Phe-Leu (-Met). In studies on pro-opioids, the brain enzyme also recognized Met-Arg, Arg-Arg, and Arg-Ile bonds; the best substrates on a relative basis were ME-Arg-Phe, LE- or ME-Arg-Arg, and LE-Arg-Arg-Ile. Measurement of kinetic values in relation to the sites of opioid cleavage provided a basis to differentiate brain cathepsins B and L. Cathepsin L acted with high affinity toward LE to cleave Gly2-Gly3 (Km 82.5 microM, kcat 2034 min-1), in contrast to low affinity cleavage by cathepsin B at Gly3-Phe4. Kapp, the second-order rate constant of enzyme inactivation by Z-Phe-Phe-CHN2 with LE as substrate was 31,530 M-1 s-1 or 10(3) higher than its effect on cathepsin B-mediated hydrolysis of ME-Arg-Phe at the Met-Arg site. Gly-Gly cleavage by cathepsin L was blocked by D-Ala2, did not require the presence of free end groups, and was the only site recognized within opioid peptides having a C-terminal Arg-COOH. The use of opioid peptides as substrates provides further insight into cathepsin L specificity. For these the susceptible sites were flanked primarily by hydrophobic and aromatic groups at P2, P2' or P3'.

Amino Acid Sequence↗
PubMed1987

Effect of charcoal and sorbitol-charcoal suspension on the elimination of intravenous phenobarbital.

The effects of two different oral charcoal suspensions on the elimination of a 200 mg/70 kg, 1 h intravenous (i.v.) infusion of phenobarbital and the tolerances of the two regimens were determined in a randomized crossover study in six healthy male volunteers. Phenobarbital was given i.v. alone or together with 105 g of oral activated charcoal suspension or with 105 g of a commercially available sorbitol-charcoal suspension over a 36-h period. A 13-34% decrease in the area under the serum concentration time curve (AUC) for 0-60 h occurred with the administration of the activated charcoal, and a 19-52% decrease occurred with the commercial sorbitol-charcoal regimen. The mean apparent systemic clearance of total phenobarbital increased from 0.089 +/- 0.019 ml/min/kg to 0.141 +/- 0.029 and 0.146 +/- 0.036 ml/min/kg with the charcoal and sorbitol-charcoal treatments, respectively. No significant change in the fraction of phenobarbital bound to protein was detected. The charcoal regimen caused constipation in one subject. All subjects taking the sorbitol-charcoal preparation experienced diarrhea; there were no changes in electrolytes with either charcoal suspension. All subjects preferred the sorbitol-charcoal preparation.

Adult↗
PubMed1987

Utilization of Km for phenytoin dosage after folate addition to patient regimen.

Phenytoin decreases serum and red blood cell folates in 50% of the patients on the anticonvulsant. The supplementation of folic acid changes the disposition of phenytoin, a drug that exhibits Michaelis-Menten kinetics. In a retrospective study at the Veterans Administration Medical Center, seven adult male folate-deficient epileptic patients on phenytoin alone and compliant with the anticonvulsant were supplemented with 1 mg oral folic acid. Before and after the addition of the vitamin, Vmax and Km were calculated for phenytoin. With folic acid, the total serum phenytoin concentration decreased significantly by an average of 22.6 +/- 13.0%. The Km decreased significantly from 6.7 +/- 1.1 to 4.1 +/- 1.5 micrograms/ml. The Vmax remained unchanged. It is hypothesized that folic acid is a cofactor in the metabolism of phenytoin. A cofactor would be expected to alter the affinity (Km) of the enzymes for phenytoin with no change in the liver's total capacity (Vmax) to metabolize phenytoin. This retrospective study in seven male epileptic patients is a convincing argument for the hypothesis.

Adult↗
PubMed1987

Phenytoin binding in healthy volunteers.

The pharmacologic effect of phenytoin is directly related to the unbound concentration in the serum, which previously has been reported in the literature to be approximately 10%. The results of 13 out of 14 20-35 year-old healthy male volunteers studied indicate that less than 10% unbound phenytoin is present in the majority of subjects taking two different doses of phenytoin.

Adult↗
PubMed1987

Parkinsonism--drug treatment: Part I.

The purpose of this two-part review is to explain current drug treatment in part I and discuss investigational drug therapy and miscellaneous drugs in the management of parkinsonism in part II. The medical approach to this disease is still based on the imbalance between a deficiency of dopamine and a functional increase in acetylcholine. Anticholinergic agents are used to treat the tremors in the early stages of the disease.

Antiparkinson Agents↗
PubMed1987

Parkinsonism--drug treatment: Part II.

This article, second in a two-part review, discusses investigational drug therapy and miscellaneous drug management of parkinsonism. Drug therapy should be individualized according to signs and changed as the disease progresses or if the patient develops intolerable side effects. Investigational drugs being examined include sustained-release and injectable dopaminergic formulations. Drug-induced parkinsonism is also examined.

Antiparkinson Agents↗
PubMed1986

Linear systems approach to the analysis of an induced drug removal process. Phenobarbital removal by oral activated charcoal.

The theory of linear systems analysis is applied to the evaluation of induced drug removal processes. The rate and extent of removal are determined by deconvolution for the case of phenobarbital removal from the systemic circulation by orally administered activated charcoal. The proposed method is model independent in the sense that no specific models of intrinsic or induced pharmacokinetic processes are required, and it is readily adapted to the analysis of most types of induced removal processes (hemodialysis, peritoneal dialysis, etc.). Application of the approach indicates that phenobarbital was removed from the systemic circulation to an extent of 25-53% following multiple oral doses of activated charcoal in healthy human subjects.

Charcoal↗
PubMed1986

Preferential action of rat brain cathepsin B as a peptidyl dipeptidase converting pro-opioid oligopeptides.

Purified rat brain cathepsin B (EC 3.4.22.1) converted prodynorphins or proenkephalins to shorter active forms by the preferential removal of C-terminal dipeptides. The substrate affinities for Met-enkephalin-Arg-Phe or -Arg-Gly-Leu were Km 46 and 117 microM, and kcat/Km ratios were 67 and 115 microM-1, min-1, respectively. Met-Enkephalin was inactivated by the same mechanism (Km-450 microM; kcat/Km = 0.12 microM-1 min-1). The comparison of cathepsin B hydrolysis for pro-opioids, a synthetic hexapeptide and its fragments, C-blocked peptides (pro-opioid amides, Met-enkephalin amide, substance P), and bovine myelin basic protein, provided information on the influence of the C-terminal residues on dipeptide release, the rates as correlated to peptide length, and the optimal arrangement of residues favoring scission at the P1-P'1 sites. The brain enzyme was stereospecific and did not act on peptides with C-terminal D-amino acid substituents. Arg hindered and Pro blocked the release of C-terminal dipeptides when in the P'2 positions. The suppression of dipeptide release by agents inhibiting endopeptidase actions such as E-64 and leupeptin, and the endogenous brain factor (cerebrocystatin) point to similar catalytic mechanisms for the exopeptidase action.

Animals↗
PubMed1986

Effect of several amino acid phosphonates and other compounds on rat brain and kidney peptidases.

A series of N-terminal phosphonate derivatives, H2O3PCHPhNHR (R = Leu, Phe, Trp, and/or Tyr), were synthesized with the aim of mimicking phosphoramidon, a potent inhibitor of enkephalinase, while avoiding the lability of the scissile P-N bond. All of the N-phosphonobenzyl derivatives of the amino acids, including the substituted succinylhydrazobenzophenone compounds, were inactive toward rat brain aminopeptidase and rat kidney carboxypeptidase. The N-monobenzylphosphonobenzyl derivatives, PhCH2OPO(OH)CHPhNHR, of individual amino acids and several of the N-phosphonobenzyl dipeptides showed inhibition in the micromolar range toward the soluble exopeptidase but were inactive with both the brain and kidney endopeptidase.

Aminopeptidases↗