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Biomedical subjects

D Rein

Publications and source records attributed to D Rein.

At least 19 recordsLinked to original sources
PubMed2004

Cholesterol-lowering properties of Ganoderma lucidum in vitro, ex vivo, and in hamsters and minipigs.

INTRODUCTION: There has been renewed interest in mushroom medicinal properties. We studied cholesterol lowering properties of Ganoderma lucidum (Gl), a renowned medicinal species. RESULTS: Organic fractions containing oxygenated lanosterol derivatives inhibited cholesterol synthesis in T9A4 hepatocytes. In hamsters, 5% Gl did not effect LDL; but decreased total cholesterol (TC) 9.8%, and HDL 11.2%. Gl (2.5 and 5%) had effects on several fecal neutral sterols and bile acids. Both Gl doses reduced hepatic microsomal ex-vivo HMG-CoA reductase activity. In minipigs, 2.5 Gl decreased TC, LDL- and HDL cholesterol 20, 27, and 18%, respectively (P < 0.05); increased fecal cholestanol and coprostanol; and decreased cholate. CONCLUSIONS: Overall, Gl has potential to reduce LDL cholesterol in vivo through various mechanisms. Next steps are to: fully characterize bioactive components in lipid soluble/insoluble fractions; evaluate bioactivity of isolated fractions; and examine human cholesterol lowering properties. Innovative new cholesterol-lowering foods and medicines containing Gl are envisioned.

Journal Article↗
PubMed2000

Influence of oligomer chain length on the antioxidant activity of procyanidins.

The antioxidant activity of catechin monomers and procyanidin (dimers to hexamers) fractions purified from cocoa was studied in two in vitro systems: liposomes and human LDL. Liposome oxidation (evaluated as formation of 2-thiobarbituric acid reactive substances) was initiated with 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH), 2,2'-azobis (2,4-dimethylvaleronitrile) (AMVN), iron/ascorbate, or UV-C; LDL oxidation (evaluated as formation of conjugated dienes) was initiated with Cu(2+) or AAPH. Catechin monomers and procyanidin fractions inhibited both liposome and LDL oxidation. Monomers, dimers, and trimers fractions were the most effective antioxidants when liposome oxidation was initiated in the aqueous phase. When oxidation was initiated in the lipid domains, higher molecular weight procyanidins were the most effective. All fractions significantly inhibited Cu-mediated LDL oxidation; no significant effect of procyanidin molecular weight was observed. The hexamer fraction was the least effective with respect to preventing AAPH initiated LDL oxidation. Results reported herein give further evidence on the influence of the oligomer chain length on the antioxidant protection by procyanidins.

Amidines↗
PubMed2000

Cocoa inhibits platelet activation and function.

BACKGROUND: Epidemiologic studies have shown inverse associations between dietary polyphenols and mortality from coronary heart disease. However, the basis for this protective association is uncertain. Food polyphenols reportedly have antioxidant properties and decrease platelet function in vitro. OBJECTIVE: This study sought to evaluate whether consumption of a polyphenol-rich cocoa beverage modulates human platelet activation and primary hemostasis. DESIGN: Peripheral blood was obtained from 30 healthy subjects before and 2 and 6 h after ingestion of a cocoa beverage (n = 10), a caffeine-containing control beverage (n = 10), or water (n = 10). Platelet activation was measured in terms of expression of activation-dependent platelet antigens and platelet microparticle formation by using fluorescent-labeled monoclonal antibodies and flow cytometry. Primary platelet-related hemostasis was measured with a platelet function analyzer. RESULTS: Ex vivo epinephrine- or ADP-stimulated expression of the fibrinogen-binding conformation of glycoprotein IIb-IIIa was lower 2 and 6 h after consumption of cocoa than before consumption. Cocoa consumption also decreased ADP-stimulated P-selectin expression. In contrast, epinephrine-induced platelet glycoprotein IIb-IIIa expression increased after consumption of the caffeine-containing beverage but not after water consumption. Platelet microparticle formation decreased 2 and 6 h after cocoa consumption but increased after caffeine and water consumption. Primary hemostasis in response to epinephrine in vitro was inhibited 6 h after cocoa consumption. The caffeine-containing beverage inhibited ADP-induced primary hemostasis 2 and 6 h after consumption. CONCLUSIONS: Cocoa consumption suppressed ADP- or epinephrine-stimulated platelet activation and platelet microparticle formation. Cocoa consumption had an aspirin-like effect on primary hemostasis.

Adenosine Diphosphate↗
PubMed2000

Epicatechin in human plasma: in vivo determination and effect of chocolate consumption on plasma oxidation status.

Diets that are rich in plant foods have been associated with a decreased risk for specific disease processes and certain chronic diseases. In addition to essential macronutrients and micronutrients, the flavonoids in a variety of plant foods may have health-enhancing properties. Chocolate is a food that is known to be rich in the flavan-3-ol epicatechin and procyanidin oligomers. However, the bioavailability and the biological effects of the chocolate flavonoids are poorly understood. To begin to address these issues, we developed a method based on HPLC coupled with electrochemical (coulometric) detection to determine the physiological levels of epicatechin, catechin and epicatechin dimers. This method allows for the determination of 20 pg (69 fmol) of epicatechin, which translates to plasma concentrations as low as 1 nmol/L. We next evaluated the absorption of epicatechin, from an 80-g semisweet chocolate (procyanidin-rich chocolate) bolus. By 2 h after ingestion, there was a 12-fold increase in plasma epicatechin, from 22 to 257 nmol/L (P < 0.01). Consistent with the antioxidant properties of epicatechin, within the same 2-h period, there was a significant increase of 31% in plasma total antioxidant capacity (P < 0.04) and a decrease of 40% in plasma 2-thiobarbituric acid reactive substances (P < 0.01). Plasma epicatechin and plasma antioxidant capacity approached baseline values by 6 h after ingestion. These results show that it is possible to determine basal levels of epicatechin in plasma. The data support the concept that the consumption of chocolate can result in significant increases in plasma epicatechin concentrations and decreases in plasma baseline oxidation products.

Adult↗
PubMed2000

Cocoa and wine polyphenols modulate platelet activation and function.

There is speculation that dietary polyphenols can provide cardioprotective effects due to direct antioxidant or antithrombotic mechanisms. We report in vitro and postingestion ex vivo effects of cocoa procyanidins, a procyanidin-rich cocoa beverage and dealcoholized red wine (DRW) on human platelet activation. In a series of in vitro studies, cocoa procyanidin trimers, pentamers or DRW (3 and 10 micromol/L) were incubated with citrated peripheral whole blood in the presence and absence of platelet agonists. Platelet activation was detected using fluorescent-labeled monoclonal antibodies recognizing the fibrinogen binding conformation of GPIIb-IIIa (referred to herein as PAC-1 binding) and the activation-dependent platelet epitope CD62P (P-selectin). The percentage of CD42a-positive platelets coexpressing PAC-1 binding and/or CD62P was determined by multiparameter flow cytometry. Procyanidin trimers, pentamers and DRW added to whole blood in vitro increased PAC-1 binding and P-selectin expression. In contrast, procyanidin trimers, pentamers and DRW inhibited the platelet activation in response to epinephrine. The effects on platelet activation of cocoa beverage and DRW consumption were also studied in healthy subjects. Citrated blood was obtained before and 2 and 6 h after the ingestion of a cocoa beverage, a caffeine-containing beverage, DRW or water. Platelet activation was measured by flow cytometry. The consumption of DRW did not affect the expression of activation-dependent platelet antigens, either unstimulated or after ex vivo activation with epinephrine. However, the consumption of DRW increased PAC-1 binding in response to 100 micromol/L ADP ex vivo. Cocoa consumption reduced platelet response to agonists ex vivo. The ingestion of water had no effect on platelet activation, whereas a caffeine-containing beverage augmented the response of platelets to epinephrine. In summary, select cocoa procyanidins and DRW added to whole blood in vitro increased expression of platelet activation markers in unstimulated platelets but suppressed the platelet activation response to epinephrine. In contrast, cocoa consumption suppressed unstimulated and stimulated platelet activation in whole blood. This suppressive effect observed on platelet reactivity may explain in part the reported cardioprotective effects of dietary polyphenols.

Adult↗
PubMed2000

Intra-arterial mitoxantrone and paclitaxel in a patient with Stewart-Treves syndrome: selection of chemotherapy by an ex vivo ATP-based chemosensitivity assay.

We report on a 72-year-old patient developing Stewart-Treves syndrome (STS) of the right arm 9 years after curative irradiation for ipsilateral stage III breast cancer. Facing the poor track record of both irradiation and chemotherapy in this highly malignant lymphangiosarcoma, amputation was recommended but refused by the patient. Therefore, limb conserving-therapy using three courses of intra-arterial mitoxantrone (MX) and paclitaxel (PTX) was attempted. This novel chemotherapy protocol was selected by pretherapeutic ex vivo ATP-based chemosensitivity testing of autologous tumor tissue. The patient experienced complete response, which was subsequent histologically confirmed by compartment resection. When developing recurrent STS outside of the perfused area 6 months after primary therapy, the patient was retested and reinduced with three other courses of intraarterial MX/PTX which again produced durable complete remission. This case demonstrates the benefit of indivdualized therapy in this prognostically desperate disease allowing both limb conservation and maintained quality of life.

Adenosine Triphosphate↗
PubMed1999

New HIV cases attributable to syphilis in the USA: estimates from a simplified transmission model.

OBJECTIVE: Because syphilis can raise the likelihood of HIV transmission and acquisition, syphilis prevention in the USA has the potential benefit of reducing the number of new cases of HIV. We developed a simplified transmission model to estimate the annual number and cost of new, heterosexually-acquired HIV cases in the USA attributable to syphilis. DESIGN: We estimated the number of heterosexual, HIV serodiscordant partnerships in which syphilis was present in 1996. The model included the probability of transmission of HIV (with and without the presence of syphilis) and other parameters based on data from recent literature. Published direct costs (HIV treatment costs including antiretroviral therapy) and indirect costs (e.g., lost productivity) per case of HIV were used to estimate the annual cost of HIV cases attributable to syphilis. The potential savings in averted HIV costs related to syphilis were used to estimate the potential benefits of a syphilis elimination program. RESULTS: In 1996, an estimated 1082 new heterosexual cases of HIV in the USA could be attributed to syphilis. These cases represented direct costs of US$ 211 million and indirect costs of US$ 541 million; yielding US$ 752 million in total costs. Over 15 years, a syphilis elimination program could save over US$ 833 million (discounted at 3% annually) in averted direct medical costs of syphilis-related HIV infections. CONCLUSIONS: If the only benefit of syphilis elimination were to prevent new HIV cases attributable to syphilis, a national syphilis elimination program costing less than US$ 833 million would probably pay for itself.

Cost of Illness↗
PubMed1999

Dose control with cell lines used for encapsulated cell therapy.

Cell therapy-use of cells to deliver active factors-is an emerging technique in treatment of neurodegenerative disease. Successful devices maintain cell viability and functionality over extended implant periods. Use of dividing cell lines to deliver therapeutic factors has been studied extensively. One emerging issue is the tendency of cells to continue proliferation within the intracapsular environment-potentially outstripping nutrient supply. This work presents a method of controlling proliferation and delivering therapeutic molecules within a dose range. The method entails encapsulation into a hollow fiber device of discrete numbers of cell-containing microcarriers. Proliferation control is attained by embedding cell-containing microcarriers in nonmitogenic hydrogels. PC-12 cells secreting L-dopa and dopamine was the model cell line tested. Feasibility of the method in controlling growth of normally rapidly dividing cells in the intracapsular environment was demonstrated in vitro and in vivo. Control nonmicrocarrier PC-12 cell devices had approximately fourfold greater expansion in cell number compared to experimental microcarrier-containing devices over 4 weeks in vitro and in vivo after implant into rat striatum. Ability to control dose released over a several-fold range was demonstrated with encapsulated PC-12 cells delivering neurotransmitters and C2C12 mouse myoblast cells delivering neurotrophic factors (CNTF).

Animals↗
PubMed1998

Effect of dietary catechin and vitamin E on aortic fatty streak accumulation in hypercholesterolemic hamsters.

Male golden Syrian hamsters were fed for 16 weeks on a hypercholesterolemic diet containing, per kg, 150 g of lipids (90 g butterfat, 35 g vitamin E-stripped corn oil and 25 g fish oil), 2 g cholesterol and either 3 IU vitamin E (3 IU E), 3 IU vitamin E and 200 mg catechin hydrate (3 IU E-200 Cat) or 30 IU vitamin E (30 IU E). More fatty streaks, measured by Oil Red O staining, were deposited in aortas of hamsters fed 3 IU E than in those fed either 3 IU E-200 Cat or 30 IU E. Lipid staining increased with plasma low-density lipoprotein cholesterol (LDL-C) in all animals. At the same concentration of LDL-C, animals fed either 3 IU E-200 Cat or 30 IU E developed less fatty streaks than those fed 3 IU E. Plasma LDL-C and total cholesterol were highest in hamsters fed 3 IU E and LDL-C and total cholesterol in animals fed 3 IU-200 Cat were not different from those fed either 3 IU E or 30 IU E. This study showed the importance of circulating plasma LDL-C on atherogenesis and the inhibitory effect on this process of both dietary vitamin E and catechin.

Animals↗
PubMed1998

Fluorescent lipid oxidation products and heme spectra index antioxidant efficacy in kidney tissue of hamsters.

Studies ranging from epidemiological to molecular suggest that dietary antioxidants protect against chronic diseases. The hypothesis was investigated that hamster kidney homogenate are better protected against induced oxidative damage after animals were fed a purified vitamin E deficient diet supplemented with 30 international units (IU) vitamin E/kg (30 IU diet) than fed the minimum required 3 IU vitamin E/kg (3 IU diet). The addition of 200 mg (+)-catechin to the 3 IU diet may offer protection. The effects of dietary (+)-catechin and alpha-tocopherol on tissue oxidizability were investigated by measuring (i) fluorescent products in lipid extracts, (ii) heme protein oxidation and (iii) heme destruction. A rapid initial increase of oxidation markers was measured over the 4 h incubation period for iron + ascorbate induced oxidation and a constant increase for lipoxygenase catalyzed products. Analysis of covariance over time and comparison at specific incubation times showed that iron + ascorbate induced homogenates from hamsters fed the 30 IU diet generated less fluorescent products and oxidized heme proteins than homogenates from the 3 IU or the 3 IU plus (+)-catechin fed animals. Incubation with lipoxygenase produced more lipid fluorescent products and heme protein oxidation in the 3 IU than in the 30 IU vitamin E group. In conclusion, supplementary dietary vitamin E but not supplementary (+)-catechin in a diet containing the minimum requirement of vitamin E for the species enhances oxidative resistance of kidney tissue.

Animals↗
PubMed1996

Multicomponent analysis of heme protein spectra in biological materials.

Absorption spectra of heme proteins in a tissue homogenate contain information about the oxidation status of the biological sample. Deconvolution of absorption spectra can be used to quantitate the amount of individual heme proteins present in the mixture. The heme spectral analysis program (HSAP), a computer spreadsheet program, was used to quantitatively calculate values for heme proteins measured spectrally (390 to 450 and 500 to 640 nm) in tissue homogenates undergoing oxidation. The amount of oxidized heme proteins obtained by HSAP can be compared to other measurements of tissue oxidation. Precise quantitation of the amount of heme proteins present in a homogenate sample provided accurate assessment of the oxidized heme proteins calculated by HSAP. This quantitation was achieved through modification of existing pyridine hemochrome methods. Input into HSAP of the total heme protein content via the pyridine hemochrome value generated reproducible values for oxidized heme proteins. The program has broad potential as a multicomponent analysis tool. Modification of HSAP led to the development of a difference spectra analysis program (DSAP) which was used to quantitate the type and amount of heme proteins observed in mitochondrial difference spectra. In the present application, HSAP and DSAP provide methods for interpreting complex spectral information of multicomponent biological samples that undergo oxidation.

Animals↗
PubMed1992

[Lumbosacral instability. The cauda equina compression syndrome in dogs].

The literature review includes a short anatomical description of the lumbosacral area, etiology, symptoms, diagnosis and therapy of CECS. Two hundred and twenty-seven large-breed dogs were examined clinically, neurologically and radiologically for diseases of the lumbosacral area. Radiological findings, such as dorsal dislocation of L7, spondylosis deformans, sloped craniodorsal contour of S1, sclerosis of the cranial plate of S1 as well as narrowing and increased density of the intervertebral foramen L7/S1 were compared with clinical and neurological results. In 15 dogs dorsal dislocation of L7 by 1 to 8 mm was found. An extended position proved to be more successful in demonstrating that finding than the flexed one. All other pathological changes were found either individually or in combination in patients with lumbosacral spondylolisthesis. One hundred and thirty-six dogs showed no sign of dorsal dislocation but all the other described changes. All detected changes have to be interpreted as instability of the lumbosacral area and resultant chronic and degenerative pathological processes. A definite correlation between spondylolisthesis of L7/S1 and compression of the cauda equina could not be found on plain radiography.

Animals↗