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Biomedical subjects

M Friedman

Publications and source records attributed to M Friedman.

At least 37 records · Page 2Linked to original sources
PubMed2001

Nutritional and health benefits of soy proteins.

Soy protein is a major component of the diet of food-producing animals and is increasingly important in the human diet. However, soy protein is not an ideal protein because it is deficient in the essential amino acid methionine. Methionine supplementation benefits soy infant formulas, but apparently not food intended for adults with an adequate nitrogen intake. Soy protein content of another essential amino acid, lysine, although higher than that of wheat proteins, is still lower than that of the milk protein casein. Adverse nutritional and other effects following consumption of raw soybean meal have been attributed to the presence of endogenous inhibitors of digestive enzymes and lectins and to poor digestibility. To improve the nutritional quality of soy foods, inhibitors and lectins are generally inactivated by heat treatment or eliminated by fractionation during food processing. Although lectins are heat-labile, the inhibitors are more heat-stable than the lectins. Most commercially heated meals retain up to 20% of the Bowman-Birk (BBI) inhibitor of chymotrypsin and trypsin and the Kunitz inhibitor of trypsin (KTI). To enhance the value of soybeans in human nutrition and health, a better understanding is needed of the factors that impact the nutrition and health-promoting aspects of soy proteins. This paper discusses the composition in relation to properties of soy proteins. Also described are possible beneficial and adverse effects of soy-containing diets. The former include soy-induced lowering of cholesterol, anticarcinogenic effects of BBI, and protective effects against obesity, diabetes, irritants of the digestive tract, bone, and kidney diseases, whereas the latter include poor digestibility and allergy to soy proteins. Approaches to reduce the concentration of soybean inhibitors by rearrangement of protein disulfide bonds, immunoassays of inhibitors in processed soy foods and soybean germplasm, the roles of phytoestrogenic isoflavones and lectins, and research needs in all of these areas are also discussed. This integrated overview of the widely scattered literature emphasizes general concepts based on our own studies as well as recent studies by others. It is intended to stimulate interest in further research to optimize beneficial effects of soy proteins. The payoff will be healthier humans and improved animal feeds.

Adult↗
PubMed2001

Application of the S-pyridylethylation reaction to the elucidation of the structures and functions of proteins.

Cysteine (Cys) and cystine residues in proteins are unstable under conditions used for acid hydrolysis of peptide bonds. To overcome this problem, we proposed the use of the S-pyridylethylation reaction to stabilize Cys residues as pyridylethyl-cysteine (PEC) protein derivatives. This suggestion was based on our observation that two synthetic derivatives formed by pyridylethylation of the SH group of Cys with either 2-vinylpyridine (2-VP) or 4-vinylpyridine (4-VP), designated as S-beta-(2-pyridylethyl)-L-cysteine (2-PEC) and S-beta-(4-pyridylethyl)-L-cysteine (4-PEC), were stable under acid conditions used to hydrolyze proteins. This was also the case for protein-bound PEC groups. Since their discovery over 30 years ago, pyridylethylation reactions have been widely modified and automated for the analysis of many structurally different proteins at levels as low as 20 picomoles, to determine the primary structures of proteins and to define the influence of SH groups and disulfide bonds on the structures and functional, enzymatic, medical, nutritional, pharmacological, and toxic properties of proteins isolated from plant, microbial, marine, animal, and human sources. Pyridylethylation has been accepted as the best method for the modification of Cys residues in proteins for subsequent analysis and sequence determination. The reaction has also been proposed to measure D-Cys, homocysteine, glutathione, tryptophan, dehydroalanine, and furanthiol food flavors. This integrated overview of the diverse literature on these reactions emphasizes general concepts. It is intended to serve as a resource and guide for further progress based on the reported application of pyridylethylation reactions to more than 150 proteins.

Animals↗
PubMed2001

A framework for developing excellence as a clinical educator.

The current emphasis on providing quality undergraduate and postgraduate medical education has focused attention on the educational responsibilities of all doctors. There is a greater awareness of the need to train doctors as educators and courses have been set up to satisfy this need. Some courses, such as those on how to conduct appraisal, are specific to one task facing a medical educator. Other courses take a broader view and relate educational theory to practice. In this paper we describe an outcome-based approach in which competence in teaching is defined in terms of 12 learning outcomes. The framework provides a holistic approach to the roles of the teacher and supports the professionalism of teaching. Such a framework provides the basis for the development of a curriculum for teaching excellence. It helps to define important competences for different categories of teachers, communicate the areas to be addressed in a course, identify gaps in course provision, evaluate courses, assist in staff planning and allow individuals to assess their personal learning needs. The framework is presented to encourage wider debate.

Curriculum↗
PubMed2001

The occurrence of sleep-disordered breathing among patients with head and neck cancer.

OBJECTIVE: To identify the incidence of obstructive sleep apnea (OSA) in patients treated for head and neck cancer. Obstructive sleep apnea is a relatively common and highly morbid condition that affects 9.1% of male and 4% of female middle-aged adults.1 Patients who have been successfully treated for head and neck cancer may often have a partially obstructed upper airway which is functional during the day, but collapses during sleep. STUDY DESIGN/METHODS: Twenty-four patients successfully treated for tumors of the tongue-base, pharynx, or supraglottic larynx were enrolled. Through OSA-related questionnaires, physical examination, and polysomnography, the incidence of OSA in this patient population was determined and compared with that of the general population. RESULTS: The incidence of OSA (91.7%) in this head and neck cancer patient population was found to be significantly (P =.001) higher than that of the general population. (In a random sampling of middle-aged adult males between the ages of 30 and 60 years old with a respiratory disturbance index (RDI) >15, the prevalence was previously reported to be 9.1%.1) Sixteen of 24 patients (72.7%) had clinically defined symptoms of sleep apnea. Ten of 24 patients (41.7%) received radiation therapy; all had an RDI >15. Eleven of the 14 patients (78.5%) who did not receive radiation therapy also had an RDI >15. Eight patients (33.3%) continue to regularly use continuous positive airway pressure with significant improvement in symptoms. CONCLUSIONS: Identification and treatment of OSA may be an important factor in improving quality of life for patients with head and neck cancer.

Body Mass Index↗
PubMed2001

A computer-assisted anatomical study of the nasofrontal region.

OBJECTIVES/HYPOTHESIS: Objectives were as follows: 1) to define the variations of the uncinate process' superior attachment, 2) to study the diameter of the frontal sinus ostium, 3) to study the prevalence of the agger nasi cells, and 4) to evaluate the side-to-side variability of these structures. STUDY DESIGN: A retrospective clinical study at a tertiary care center. METHODS: One hundred forty-four consecutive computed tomography scans were studied with image-guided surgery software (InstaTrak, Visualization Technology, Inc., Wilmington, MA) that provides continuous coronal, sagittal, and axial sections. We reported the superior attachment sites of the uncinate process, the diameter of the frontal sinus ostium, and prevalence of the agger nasi cells. RESULTS: The uncinate process' main superior attachment into the surrounding structures was found to have the following distribution: 52% to the lamina papyracea, 18.5% to the posteromedial wall of the agger nasi cell, 17.5% to the lamina papyracea and the junction of the middle turbinate with the cribriform plate, 7% to the junction of the middle turbinate with the cribriform plate, 3.6% to the ethmoid roof, and 1.4% to the middle turbinate. The frontal ostium anterior-posterior diameter (mean +/- SD) was 7.22 +/- 2.78 mm and its transverse diameter (mean +/- SD) was 8.92 +/- 2.95 mm. Agger nasi cells were found in 78% of the scans. CONCLUSIONS: The frontal sinus opens into the middle meatus medial to the uncinate process in 88% of the patients and lateral to the uncinate process in 12% of the patients. The naturally wide dimensions of the frontal ostium help to explain why postoperative patency can be achieved merely by exposing the ostium without the need to enlarge it. The frontal ostium dimensions in one side may differ considerably from the contralateral side. An agger nasi cell or a terminal recess, or both, are found in most cases. Image-guided surgery software is a helpful new tool for anatomical studies and for preoperative evaluation.

Cephalometry↗
PubMed2001

Tumor necrosis factor receptor deficiency alters matrix metalloproteinase 13/tissue inhibitor of metalloproteinase 1 expression in murine silicosis.

Murine exposure to silica is associated with enhanced tumor necrosis factor alpha (TNF-alpha) expression and matrix deposition. The regulation of TNF is mediated through TNF receptor (TNFR) activation of transcription factors. In the present work we have studied the importance of the individual TNFR in silica-induced lung inflammation and matrix deposition in mice. We studied RNA expression of TNF, alpha1(I) collagen, interstitial collagenase (MMP-13), and its inhibitor (TIMP-1) in the lungs of silica-treated mice. Furthermore, we correlated MMP-13/TIMP-1 RNA abundance with activation of the transcription factors AP-1 and NF-kappaB in the lungs of C57BL/6 mice, and of mice deficient in one of the two types of TNFR (p55(-/-) or p75(-/-)), exposed to silica (0.2 g/kg) or saline by intratracheal instillation. Animals were killed 28 d after exposure and lung hydroxyproline (HP), TNF, alpha1(I) collagen, MMP-13, and TIMP-1 RNA abundance was measured. AP-1 and NF-kappaB activation was studied by gel-shift assays. Compared with C57BL/6 mice, p55(-/-) and p75(-/-) mice significantly (*p < 0.05) decreased lung HP accumulation in response to silica. All murine strains enhanced TNF and alpha1(I) collagen mRNA in response to silica. Enhanced (p < 0.05) MMP-13 RNA expression was also observed in all murine strains in response to silica. Enhanced (p < 0.05) TIMP-1 RNA expression was observed in C57BL/6 mice, but not in p55(-/-) or p75(-/-) mice, in response to silica. NF-kappaB activation was observed in all murine strains, whereas AP-1 activation was observed only in C57BL/6 mice after silica treatment. These data suggest that TNFR deletion modifies MMP-13/ TIMP-1 expression in favor of matrix degradation.

Animals↗
PubMed2001

Use of a long-acting inhaled beta2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a condition in which continuous bronchodilation may have clinical advantages. This study evaluated salmeterol, a beta-agonist bronchodilator with a duration of action substantially longer than that of short-acting beta-agonists, compared with ipratropium, an anticholinergic bronchodilator, and placebo in patients with COPD. Four hundred and five patients with COPD received either salmeterol 42 microg twice daily, ipratropium bromide 36 microg four times daily, or placebo for 12 wk in this randomized, double-blind, parallel-group study. Patients were stratified on the basis of bronchodilator response to albuterol (> 12% and > 200-ml improvement) and were randomized within each stratum. Bronchodilator response was measured over 12 h four times during the treatment period. Salmeterol provided similar maximal bronchodilatation to ipratropium but had a longer duration of action and a more constant bronchodilatory effect with no evidence of bronchodilator tolerance. Both active treatments were well tolerated. Salmeterol was an effective bronchodilator with a consistent effect over this 12-wk study in patients with COPD, including those "unresponsive" to albuterol. The long duration of action of salmeterol offers the advantage of twice daily dosing compared with the required four times a day dosing with ipratropium.

Adrenergic beta-Agonists↗
PubMed2001

Economic burden of chronic obstructive pulmonary disease. Impact of new treatment options.

The incidence, morbidity and mortality of chronic obstructive pulmonary disease (COPD) is rising throughout the world. The total economic cost of COPD in the US in 1993 was estimated to be over $US15.5 billion, with $US6.1 billion for hospitalisation, $US4.4 billion for physician and other fees, $US2.5 billion for drugs, $US1.5 billion for nursing home care and $US1.0 billion for home care. Office visits, hospital outpatient visits and emergency department visits accounted for 17.3% of the direct costs for COPD in the US. When stratified by severity, COPD treatment costs strongly correlate with disease severity. The American Thoracic Society, the European Respiratory Society and the British Thoracic Society have developed guidelines for the pharmacological treatment of COPD. However, the guidelines establish inhaled bronchodilators (anticholinergic agents and beta 2-adrenergic agonists) as the mainstay of therapy for patients with COPD. The guidelines were not based on cost analyses and thus are not a priori cost-effective guidelines. Since the publication of these guidelines, several new pharmacological products have been approved for use in patients with COPD including a combination of an anticholinergic and selective beta 2-adrenergic agonist [ipratropium/salbutamol (albuterol)] and a long-acting beta 2-adrenergic agonist (salmeterol). Both products are effective bronchodilators in COPD. The purpose of this report is to place these new agents in an updated pharmacological guideline scheme, utilising recently published data on clinical efficacy as well as pharmacoeconomics. The annualised healthcare costs were computed to be $US788/patient/year for the combination ipratropium/salbutamol inhaler and $US1059/patient/year for salmeterol (1999 values). Based upon an improved understanding of the complexity of COPD, the response of patients to newer bronchodilators (given individually or in combination), and recent pharmacoeconomic data for COPD treatment, a new treatment algorithm with associated costs is proposed. The use of an algorithm, based on medical and pharmacoeconomic data, will improve lung function in patients with COPD, improve patient satisfaction (e.g. quality of life, dyspnoea) and outcomes (e.g. exacerbations). It will also result in a positive effect on healthcare costs.

Algorithms↗
PubMed2001

Potential short-term economic benefits of improved glycemic control: a managed care perspective.

OBJECTIVE: There are limited data relating glycemic control to medical costs among patients with diabetes. The goal of this study was to examine the potential impact of improved glycemic control on selected short-term complications of diabetes and associated costs in a managed care setting. RESEARCH DESIGN AND METHODS: Using a retrospective cohort design and automated databases from January 1994 to 30 June 1998, adult members of the Fallon Clinic who were diagnosed with diabetes were identified and assigned to one of three study groups based on each patient's mean HbA1c level: good control (<8%), fair control (8-10%), and poor control (> 10%) groups. Inpatient (hospital or skilled nursing facility) admissions for selected acute (short-term) complications, represented by selected infections, hyperglycemia, hypoglycemia, and electrolyte disturbances, and the associated medical charges were evaluated across the three HbA1c groups. Multivariate analyses were used to control for differences in several potential confounding factors among the study groups. All findings were expressed on a 3-year basis. RESULTS: Of 2,394 patients with diabetes, approximately 10% (251) had at least one inpatient stay for a short-term complication, accounting for 447 admissions. Over 3 years, the adjusted rate of inpatient treatment ranged from 13 per 100 patients with good glycemic control to 16 per 100 patients with fair glycemic control and 31 per 100 patients with poor glycemic control (P < 0.05). The corresponding mean adjusted charges were approximately $970, $1,380, and $3,040, respectively Among the 30% of the study population with long-term diabetic complications, the results were more marked; the adjusted admissions per 100 patients (mean charges) were estimated to be 30 ($2,610), 38 ($3,810), and 74 ($8,320) over 3 years for patients with an HbA1c of <8, 8-10, and > 10%, respectively. CONCLUSIONS: In typical practice, better glycemic control is associated with a reduced rate of admission for selected short-term complications and, therefore, reduced medical charges for these complications over a 3-year period. The potential short-term economic benefits are important to consider when making decisions regarding the adoption and use of new interventions for the management of diabetes.

Adult↗
PubMed2001

Family ties.

Explore the source record for details and available documents.

Arkansas↗
PubMed2000

Structure and hydration properties of hydroxypropyl methylcellulose matrices containing naproxen and naproxen sodium.

The present study was conducted to obtain a deeper insight into the mechanism of drug release from HPMC matrices. The microstructure, mobility, internal pH and the state of water within the gel layer of hydrated HPMC matrices (having different molecular weights) containing naproxen sodium (NS) and naproxen (N) were studied using Electron Paramagnetic Resonance (EPR), Nuclear Magnetic Resonance (NMR) and Differential Scanning Calorimetry (DSC) techniques. The study show that matrices composed of various viscosity grades of HPMC are characterized by similar microviscosity values in spite of the difference in their molecular weight. The NMR and DSC results led to the conclusion that higher molecular weights of HPMC are characterized by higher water absorption capacity and higher swelling. Analysis of non-freezable water in HPMC(K4M)-NS system revealed that addition of NS to solution increased the fraction of water bound to K4M+NS compared with the equivalent solutions without NS. The results suggest that the drug is participating in the crystallization of water and leads to the formation of a three dimensional network structure that decreases the freedom of water in K4M+NS samples. Calculation of the number of hydration shells showed that up to 2.2 layers are involved in HPMC-NS hydration compared to 1.5 layers for HPMC gel without NS. This was explained based on the different water ordering in the gel induced by NS as results of its absorption to polymer surface. Microviscosity values measured by EPR for K4M/N and K4M/NS hydrated matrices were found to be higher for K4M/N matrices, especially at initial stage of hydration. Mobile compartment calculations showed lower values for K4M/N compared with K4M/NS matrices. pH measurements by EPR revealed that incorporation of N to HPMC matrix led to lower internal pH value inside the hydrated tablet compared with NS. This behavior led to lower solubility of N which dictates its surface erosion mechanism, compared with NS matrix that was characterized by higher internal pH value and higher drug solubility. These properties of HPMC/NS increased chain hydration and stability, and led to drug release by the diffusion mechanism.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

The effect of egg albumin on the crystalline properties of carbamazepine in sustained release hydrophilic matrix tablets and in aqueous solutions.

The influence of egg albumin (EA) on the crystal habit properties of carbamazepine (CBZ) in aqueous solutions, solid-state, and in sustained release matrix tablets was investigated using differential scanning calorimetry (DSC), hot-stage microscopy (HSM), X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and contact angle goniometer (CAG). The results suggest that in solid-state mixtures, EA affected the polymorphic transitions of CBZ from the beta to the alpha form. In hydrated matrix tablets and aqueous solutions, EA influenced the conversion rate of CBZ to the dihydrate form depending on EA concentration. It was found that increasing EA concentration enhanced CBZ dihydrate aggregation, an effect that leads to the formation of crystals with high mechanical strength and decrease of CBZ solubility. Possible mechanisms, which explain crystal growth and aggregation, as well as alteration of CBZ polymorphic transitions in the solid-state, gel layer, and in aqueous solution were suggested. In the gel layer of hydrated tablets the kinetics of CBZ transformation to the dihydrate form, crystal growth and aggregation were influenced by various processes: matrix hydration, erosion mechanism and the formation of metastable conditions, which favor aggregation and growth. The release kinetics of CBZ from the matrix highly correlated with the crystalline and morphological changes occurring in the matrix.

Anticonvulsants↗
PubMed2000

Correlation between drug release kinetics from proteineous matrix and matrix structure: EPR and NMR study.

The present study was conducted in order to probe the microstructure, microviscosity, and hydration properties of matrices containing two model drugs, naproxen sodium (NS) and naproxen (N), and egg albumin (EA) as matrix carrier. The results suggested that N release from EA matrix was controlled by a bulk erosion mechanism in combination with additional processes (crystal dissolution/crystallization rate) compared with NS matrix, which behaved as a non-erodible matrix and drug release occurred by diffusion through the gel. Using EPR technique it has been shown that incorporating NS into EA matrix strongly influences the microstructure of the protein gel, and hence the transport of the penetrant within the matrix, compared with matrices containing N. The presence of NS increased the protein chain mobility and hydration which supports our previous results showing that NS cause unfolding of EA. In contrast, N caused only marginal effect on EA chain mobility. The gel formed in EA/NS matrices was more porous compared with EA/N matrices as revealed by the lower rotational correlation time of PCA (lower microviscosity) in EA/NS matrices compared with EA/N. However, EA/N gelled matrices were more heterogeneous, i.e., containing a higher number of components having different mobility. The T(1) and T(2) relaxation studies by NMR provided an additional support for the higher chain hydration in EA/NS matrices compared with EA/N as indicated by the higher relaxation rates in the gelled matrices. Internal pH measurements by EPR revealed that the micro-pH inside 100% EA and 50/50 EA/N matrices were lower than 50/50 EA/NS matrices and in all cases lower than the penetrating buffer pH. The lower pH compartment formed in N matrices affected N solubility and crystal dissolution rate, which can explain its lower release rate compared with EA, from the same formulation. The EPR and NMR data supports our findings that NS caused unfolding of the protein, affected matrix structure, and converted it to a hydrophobic non-erodible matrix compared with EA/N matrix in which the native properties of EA were mainly retained.

Diffusion↗
PubMed2000

Pharmacodynamic effects of bezafibrate and niacin combination: implications of the mode of administration.

The goal of this investigation was to optimize antilipid therapy by utilizing the combined activity of two lipid-lowering agents, niacin and bezafibrate, and improve their efficacy by targeting them to their presumed presystemic site(s) of action. Thus, continuous duodenal (IGI) administration of the drug combination should augment their efficacy in comparison with intermittent oral treatment. Three hyperlipidemic rat models were studied: Models A and B were based on cholesterol-enriched diets and Model C was based on on acute hyperlipidemia induced by triton injection. Continuous IGI administration of the drug combination [bezafibrate, 30mg/kg/day, and niacin, 40 mg/kg/day for 3 days (Models A and B) or for 18 h (Model C)] produced significantly greater lowering of total cholesterol and triglycerides and elevation of high-density lipoprotein (HDL) cholesterol in comparison with intermittent oral administration of the same doses either given individually or in combination (Models A and B). Similar results were found in Model C for the IGI administration of the drug combination in contrast to oral and also to intravenous infusions. The results indicate that the combination of bezafibrate and niacin produces a significant hypolipidemic response, with major site(s) of action located presystemically. Because a slow-release matrix tablet of the drug combination resulted in a similar magnitude of effect as the IGI administration, the present study provides a pharmacodynamic rationale for the use of a slow-release low-dose niacin-bezafibrate combination.

Animals↗
PubMed2000

Effect of improved nasal breathing on obstructive sleep apnea.

OBJECTIVES: The goal was to compare the effect of an improved nasal airway on obstructive sleep apnea (OSA) by use of subjective and objective measures. METHODS: A prospective study of 50 consecutive patients with nasal airway obstruction and OSA was carried out. RESULTS: Subjectively, nasal breathing improved in 49 (98%) patients, whereas snoring decreased or disappeared in 17 (34%); the remaining 33 (66%) patients did not notice any significant change in their snoring. Daytime energy levels increased in 39 (78%) patients and remained unchanged or worsened in 11 (22%). In review of the polysomnographic data, the group overall did not have significant changes in respiratory disturbance index (RDI) or lowest oxygen saturation levels (LSaO(2)). Continuous positive airway pressure (CPAP) levels required to correct OSA decreased after nasal surgery (P < 0.01). Patients with mild OSA showed significant worsening in RDI (P < 0.05), whereas LSaO(2) levels were improved in the group with moderate OSA (P < 0.05). In patients with severe OSA neither the RDI levels nor the LSaO(2) changed, but CPAP levels required to alleviate the obstruction after surgery were reduced (P < 0.01). CONCLUSIONS: Most patients report improvement in nasal and sleep symptoms after correction of nasal airway obstruction. However, nasal surgery alone does not consistently improve OSA when measured objectively. Depending on the severity of OSA, nasal airway reconstruction may contribute to a decrease in CPAP level and improvement in oxygen saturation. Correction of the obstructed nasal airway should certainly be included in the overall treatment plan for OSA.

Adult↗
PubMed2000

Lowering of plasma LDL cholesterol in hamsters by the tomato glycoalkaloid tomatine.

Tomatoes contain the steroidal glycoalkaloid tomatine, which has been reported to form strong, insoluble complexes with cholesterol in vitro. To determine whether tomatine can reduce dietary cholesterol absorption and plasma levels of cholesterol and triglycerides, we fed hamsters a high-fat, high-cholesterol diet with 0.05-0.2% added tomatine in the diet. The tomatine diets induced lowering of serum low-density lipoprotein (LDL) without changing high-density lipoprotein (HDL) cholesterol. Compared to the control diets, four- to fivefold more labeled dietary cholesterol and coprostanol was excreted in the feces of the tomatine-fed hamsters. The amount of cholesterol excreted in the feces corresponded to the amount of tomatine in the diet. These observations suggest that due to the formation of an insoluble tomatine-cholesterol complex and its excretion in the feces, very little dietary tomatine is absorbed from the digestive tract into the blood stream. They are also consistent with the reported low oral toxicity of tomatine compared to other glycoalkaloids.

Administration, Oral↗
PubMed2000

The folic acid analogue methotrexate protects frog embryo cell membranes against damage by the potato glycoalkaloid alpha-chaconine.

As part of an effort to improve the safety of plant foods, a need exists to more clearly delineate the mechanisms of toxicities of glycoalkaloids, which may be present in Solanum plant species such as potatoes, tomatoes and eggplants. Alpha-chaconine is a major glycoalkaloid present in potatoes. To assess the possible influence of structure of pteridine derivatives on toxicity of potato glycoalkaloids, a previous study that demonstrated the protective effects of folic acid against the Solanum glycoalkaloid alpha-chaconine-induced toxicity on Xenopus laevis frog embryo cell membranes was extended to two folate analogues--a synthetic compound widely used as a therapeutic agent methotrexate, and naturally occurring L-monapterin. Adverse effects on embryos were evaluated by observing changes in membrane potentials with an electrochromic dye, di-4-ANEPPS, as a fluorescent probe for the integrity of the membranes. Methotrexate decreased alpha-chaconine-induced polarization, as did folic acid. This decrease may result from an alteration of membrane conformations that prevents the binding of the glycoalkaloid to the membrane receptor sites, and/or from effects on folic acid metabolism. In contrast, L-monapterin did not significantly reduce the alpha-chaconine-induced toxicity. The possible significance of these results to food safety is discussed.

Animals↗