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Biomedical subjects

A Bader

Publications and source records attributed to A Bader.

At least 55 records · Page 3Linked to original sources
PubMed2000

Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits: in vivo restoration of valve tissue.

BACKGROUND: Tissue engineering using in vitro-cultivated autologous vascular wall cells is a new approach to biological heart valve replacement. In the present study, we analyzed a new concept to process allogenic acellular matrix scaffolds of pulmonary heart valves after in vitro seeding with the use of autologous cells in a sheep model. METHODS AND RESULTS: Allogenic heart valve conduits were acellularized by a 48-hour trypsin/EDTA incubation to extract endothelial cells and myofibroblasts. The acellularization procedure resulted in an almost complete removal of cells. After that procedure, a static reseeding of the upper surface of the valve was performed sequentially with autologous myofibroblasts for 6 days and endothelial cells for 2 days, resulting in a patchy cellular restitution on the valve surface. The in vivo function was tested in a sheep model of orthotopic pulmonary valve conduit transplantation. Three of 4 unseeded control valves and 5 of 6 tissue-engineered valves showed normal function up to 3 months. Unseeded allogenic acellular control valves showed partial degeneration (2 of 4 valves) and no interstitial valve tissue reconstitution. Tissue-engineered valves showed complete histological restitution of valve tissue and confluent endothelial surface coverage in all cases. Immunohistological analysis revealed cellular reconstitution of endothelial cells (von Willebrand factor), myofibroblasts (alpha-actin), and matrix synthesis (procollagen I). There were histological signs of inflammatory reactions to subvalvar muscle leading to calcifications, but these were not found in valve and pulmonary artery tissue. CONCLUSIONS: The in vitro tissue-engineering approach using acellular matrix conduits leads to the in vivo reconstitution of viable heart valve tissue.

Animals↗
PubMed2000

High level benzodiazepine and ammonia clearance by flat membrane bioreactors with porcine liver cells.

The onset of hepatic encephalopathy is a multifactorial process in which endogenous benzodiazepines and hyperammonemia play a pivotal role. The treatment of comatose states in liver failure is one of the major functions of a bioartificial liver. A controlled study demonstrating the capacity of a large scale bioartificial liver to detoxify benzodiazepines could be a crucial prerequisite to break this circle of events leading to coma. The aim of this study was therefore to expose the bioreactor to high levels of benzodiazepines and ammonia for evaluation of its detoxifying capacity. We have developed a novel and unique device reconstructing the plate architecture of the liver. Porcine hepatocytes were co-cultured with non-parenchymal cells. We investigated benzodiazepine metabolism using diazepam as model drug. The bioreactor was also loaded with high levels of ammonia and ammonia clearance as well as urea secretion with ammonia challenge were investigated. Albumin secretion was analysed in parallel as a control viability and tissue specific secretory parameter. The results clearly show that the velocity of diazepam turnover increases between day 1 and 2 and stabilises at high levels. Typical diazepam metabolites including temazepam, N-desmethyl-diazepam and oxazepam were generated. Cell specific functions, including albumin secretion, were comparable to an in vivo liver. We conclude that the flat membrane bioreactor used as bioartificial liver has the potential to detoxify diazepam and ammonia at significant amounts. Maintenance of monoxygenase activities in vitro is one of the strongholds of the bioreactor concept presented in this study.

Albumins↗
PubMed2000

Engineering of human vascular aortic tissue based on a xenogeneic starter matrix.

BACKGROUND: The goal for tissue engineering of vascular grafts is the replacement of a diseased vessel with a functional and stable graft. We now introduce a new concept for the tissue engineering of vessels. The idea was to humanize a previously acellularized, but structurally intact, xenogeneic vessel by repopulation with human autologous cells. To this purpose, a gentle nondenaturing and nondeterging acellularization procedure for xenogeneic aortas was developed. This structure was reseeded with pre-expanded peripheral vascular endothelial cells (EC) and myofibroblasts using specifically designed bioreactors. METHODS: Aortas from 15-30 kg female landrace pigs were acelullarized with a 0.1% trypsin solution for between 24 and 96 hr. Human vascular cells were harvested from saphenous vein biopsy specimens. Acellularized vessels were reseeded with EC and myofibroblasts. Cell viability after reseeding was assayed by fluorescence staining. Morphologic features of the acellularized matrix and tissue engineered vessel was assayed by transmission and scanning electron microscopy and histologic analysis. Nitric oxide-synthetase activity was investigated by mass spectrometric analysis of bioreactor supernatants. The in vivo immune response was tested by subcutaneous implantation of acellularized porcine aortic tissue in a rat model. RESULTS: The acellularization procedure resulted in an almost complete removal of the original resident cells, and the 3-D matrix was loosened at interfibrillar zones. However, the 3-D arrangement of the matrix fibers was grossly maintained. The 3-D matrix was covered with a fully confluent human endothelial cell layer obtained by continuous stress challenge in the bioreactor. Myofibroblasts migrated into positions formerly occupied by the xenogeneic cells. Nitric oxide synthetase activity was maintained in the bioartificial graft. T-lymphocyte and CD18 positive leukocyte infiltrate were greatly reduced after acellularization of porcine aortic specimens after implantation in the rat. CONCLUSIONS: Porcine vessels were acellularized and consecutively fully repopulated with human EC and myofibroblasts. This approach may eventually lead to the engineering of vessels immunologically acceptable to the host using a relatively short preparation period of 2-3 weeks. We expect matrix turnover in vivo leading to a gradual assimilation of the matrix structure by the host mediated by the hosts autologous cells.

Animals↗
PubMed2000

Genome search for susceptibility loci of common idiopathic generalised epilepsies.

Genetic factors play a major role in the aetiology of idiopathic generalised epilepsies (IGEs). The present genome scan was designed to identify susceptibility loci that predispose to a spectrum of common IGE syndromes. Our collaborative study included 130 IGE-multiplex families ascertained through a proband with either an idiopathic absence epilepsy or juvenile myoclonic epilepsy, and one or more siblings affected by an IGE trait. In total, 413 microsatellite polymorphisms were genotyped in 617 family members. Non-parametric multipoint linkage analysis, using the GeneHunter program, provided significant evidence for a novel IGE susceptibility locus on chromosome 3q26 (Z(NPL) = 4.19 at D3S3725; P = 0.000017) and suggestive evidence for two IGE loci on chromosome 14q23 (Z(NPL) = 3.28 at D14S63; P = 0.000566), and chromosome 2q36 (Z(NPL) = 2.98 at D2S1371; P = 0.000535). The present linkage findings provide suggestive evidence that at least three genetic factors confer susceptibility to generalised seizures in a broad spectrum of IGE syndromes. The chromosomal segments identified harbour several genes involved in the regulation of neuronal ion influx which are plausible candidates for mutation screening.

Chromosomes, Human, Pair 14↗
PubMed2000

Leukemia inhibitory factor modulates cardiogenesis in embryoid bodies in opposite fashions.

Cardiogenesis is a multistep process regulated by a hierarchy of factors defining each developmental stage of the heart. One of these factors, leukemia inhibitory factor (LIF), a member of the interleukin-6 family of cytokines, is expressed in embryonic and neonatal cardiomyocytes and induces cardiomyocyte hypertrophy. Many aspects of embryogenesis are faithfully recapitulated during in vitro differentiation of embryonic stem cells in embryoid bodies. We exploited this model to study effects of growth factors on commitment and differentiation of cardiomyocytes and on maintenance of their phenotype. We identified LIF as a factor affecting commitment and differentiation of cardiomyocytes in an opposite manner. Diffusible LIF inhibited mesoderm formation and hampered commitment of cardiomyocytes. Lack of both the diffusible and matrix-bound isoforms of LIF in lif-/- embryoid bodies did not interfere with commitment, but it severely suppressed early differentiation of cardiomyocytes. Onset of differentiation was rescued by very low concentrations of diffusible LIF; however, consecutive differentiation was attenuated in a concentration-dependent manner by diffusible LIF both in wild-type and lif-/- cardiomyocytes. Differentiation of cardiomyocytes was severely hampered but not completely blocked in lifr-/- embryoid bodies, suggesting additional, LIF-receptor ligand independent pathways for commitment and differentiation of cardiomyocytes. At the fully differentiated state, both paracrine and autocrine LIF promoted proliferation and increased longevity of cardiomyocytes. These findings suggest that both paracrine and autocrine and both diffusible and matrix-bound isoforms of LIF contribute to the modulation of cardiogenesis in a subtle, opposite, and developmental stage-dependent manner and control proliferation and maintenance of the differentiated state of cardiomyocytes.

Animals↗
PubMed2000

Cellular activity of resident macrophages during Wallerian degeneration.

The resident macrophages have been accepted as an important component of the peripheral nervous system as Schwann cells. To elucidate their role during Wallerian degeneration without interference from extrinsic hematogenous macrophages, we designed a culture system to investigate the behavior of resident macrophages in vitro. A total of 75 adult male Lewis rats were used; 2. 5-cm-length sciatic nerve explants were harvested. There were three groups. In the culture groups, the nerve explants were incubated in Dulbecco's modified Eagle's medium (DMEM) only or in DMEM supplemented with 2 microm forskolin and 10 microg/ml pituitary extract (mitogenic medium for Schwann cells). In vivo predegenerated nerves and normal nerves were used as the positive and negative controls, respectively. The observation periods extended to 3 weeks. Hematoxylin and eosin (H&E) stain was employed to estimate overall cell number in nerve explants. Macrophages were labeled with ED1; S-100 immunostaining was used to evaluate the presence of Schwann cells during Wallerian degeneration. Trichrome stain and toluidine blue stain were used to visualize the fate of myelin. In the culture groups, the number of resident macrophages increased continuously, although there were significantly fewer resident macrophages than hematogenous macrophages after 3 days of Wallerian degeneration (P < 0.01). Morphologically, resident macrophages contained densely small ED1-positive granules within their cytoplasm, even at later stages of observation, whereas hematogenous macrophages contained typical large ED1-positive foam vacuoles characteristic of their mature phagocytic ability. The cellular activity of Schwann cells was well preserved in the mitogenic medium; however, myelin removal was not significantly enhanced as compared with the DMEM groups (P > 0.05). The clearance of myelin debris was shown to be incomplete in culture groups as compared with the complete removal of myelin debris in the in vivo groups. Resident macrophages were actively involved in Wallerian degeneration, but their phagocytic and proliferation ability was limited. Schwann cells played an adjunctive role during the removal of myelin debris.

Animals↗
PubMed2000

Primary porcine enterocyte and hepatocyte cultures to study drug oxidation reactions.

1. Primary porcine hepatocytes and enterocytes were isolated and cultured in Williams' E medium for up to 10 days to investigate potential organ differences in the metabolism of the immunosuppressive compound tacrolimus (FK 506) and of two investigational drugs (KC11346 and KC12291). Using LC-MS (FK506) and HPLC-FL (KC 11346/12291) a number of metabolites with identical mass and/or identical retention time could be detected. 2. In the case of tacrolimus hepatocytes and enterocytes produced the same spectrum of metabolites, e.g. bisdemethyl-tacrolimus, demethyl-tacrolimus, demethyl-hydroxy-tacrolimus and hydroxy-tacrolimus, albeit at varying intensities. 3. Treatment of enterocyte cultures with dexamethasone increased the overall metabolite formation very significantly (up to 36 fold). 4. The metabolism of tacrolimus was also studied with preparations of insect cells, that express specifically high levels of individual human cytochrome P450 (CYP) isoenzymes. All metabolites could be generated with microsomal preparations specifically expressing CYP3A4, but hydroxy-tacrolimus was exclusively produced by CYP3A5. 5. In the case of the investigational drugs KC 11346 and KC 12291 only three metabolites were formed by cultured enterocytes whereas hepatocytes produced 10 and 20 metabolites, respectively. 6. When assessed at the protein level CYP1A and CYP3A were expressed in cultures of porcine enterocytes for up to 10 days but porcine hepatocytes expressed additionally CYP2C9/10. 7. In conclusion, primary enterocytes and hepatocytes can be successfully cultured for several days while maintaining mono-oxygenase activity and may therefore be used as a tool for studying intestinal and hepatic metabolism.

Animals↗
PubMed2000

Tissue engineering of vascular grafts: human cell seeding of decellularised porcine matrix.

OBJECTIVES: To develop a biocompatible and mechanically stable vascular graft combining human cells and a xenogenic acellular matrix. DESIGN/MATERIALS: Decellularised matrix tubes were obtained by enzymatic cell extraction of native porcine aortas. Endothelial cells and myofibroblasts were isolated from human saphenous veins and grown in cell cultures. The inner surface of the tubes was seeded with endothelial cells or myofibroblasts and exposed to pulsatile flow. RESULTS: After cell extraction, the absence of cellular components, as well as the maintenance of matrix integrity, was demonstrated by means of light microscopy and scanning electron microscopy. Furthermore, the porcine matrix was successfully seeded with human endothelial cells, which grew to a monolayer under flow conditions. Stable biomechanical properties were achieved at physiological perfusion pressures in vitro. CONCLUSIONS: Cellular components can be extracted from native porcine blood vessels. Vascular grafts can be generated in vitro of animal acellular matrix and human cells.

Animals↗
PubMed2000

Cytochrome P450 enzyme activity and protein expression in primary porcine enterocyte and hepatocyte cultures.

1. A method for the isolation and cultivation of porcine hepatocytes and porcine duodenal enterocytes for the investigation of drug oxidation reactions has been established. 2. Hepatocytes as well as enterocytes metabolized ethoxyresorufin (EROD) and ethoxycoumarin (ECOD) effectively, the rate being 31+/-17 pmol/h x dish (EROD) and 9530+/-4062 pmol/h x dish (ECOD) in the case of hepatocytes, and 9+/-4 pmol/h x dish (EROD) and 510+/-467 pmol/h x dish (ECOD) in the case of enterocytes. Diazepam, another CYP monooxygenase substrate, was also metabolized by porcine hepatocytes but not with porcine enterocytes, thus indicating differences in the metabolic competence of the liver and the gut. 3. The ability to induce enzymes responsible for the metabolism of ethoxyresorufin and ethoxycoumarin was investigated in vitro on treatment of the cell cultures with either 50 microM 3-methylcholanthrene (3-MC) or 50 microM beta-naphthoflavone (beta-NF). With enterocyte cultures, ECOD activity was inducible up to 20-fold, whereas EROD remained unchanged following treatment with either 3-MC or beta-NF. 4. Western blotting provided additional evidence for the expression of CYP1A1 and CYP3A4 at the protein level and treatment of cultured enterocytes with 30 microM Aroclor 1254 or 50 microM beta-NF resulted in enhanced expression of the CYP1A protein, and CYP3A4 protein expression was induced following treatment with 50 microM DEX, 2 mM PB, 30 microM Aroclor 1254 or 50 microM beta-NF. 5. The metabolism of diazepam was also investigated with baculovirus-expressed human CYP enzymes (2C8, 2C9-ARG, 2C9-CYS, 2C19, 3A4, 3A4+cytochrome b5 and 3A5) and evidence was obtained to suggest the formation of temazepam and oxazepam by enzymes of the CYP3A subfamily. Small amounts (32+/-12 ng/ml) of desmethyldiazepam were additionally recovered in microsomal preparations of all CYP-transfected cell lines. 6. In conclusion, porcine duodenal enterocytes can successfully be cultured for a short period and may be used as a tool for studying intestinal metabolism, whereas porcine hepatocytes can be cultured for prolonged periods (>10 days) reliably to investigate hepatic drug oxidation reactions.

Albumins↗
PubMed2000

In vitro model of the human liver parenchyma to study hepatotoxic side effects by Dy-EOB-DTPA.

RATIONALE AND OBJECTIVES: In vivo studies have shown species-specific toxicity after application of the liver-specific contrast agent Dy-ethoxybenzyl (EOB)-DTPA. To predict species differences in the laboratory, an in vitro model of the liver was used to examine the divergent results. METHODS: Rat, canine, porcine, and human hepatocytes were isolated and embedded between layers of collagen. During and after 48 hours of incubation with different concentrations of Dy-EOB-DTPA (maximum concentration 50 mmol/L), morphological changes and enzyme leakage were determined. RESULTS: The response to the contrast agent varied for hepatocytes from different species. For canine cells, morphological changes and cell death were evident with as little as 5 mmol/L Dy-EOB-DTPA. Rat hepatocytes tolerated up to 50 mmol/L Dy-EOB-DTPA, and enzyme leakage was transient. Only after incubation with 50 mmol/L Dy-EOB-DTPA was the formation of intracellular vacuoles evident. In contrast, even the highest concentration of Dy-EOB-DTPA did not cause an enzyme leakage of porcine or human hepatocytes, although similar vacuoles were seen. CONCLUSIONS: These data demonstrate a species-dependent toxicity for Dy-EOB-DTPA in vitro, with similar responses in porcine and human hepatocytes.

Animals↗
PubMed2000

Prevalence of endocrine dysfunction in HIV-infected men.

OBJECTIVE: Endocrine dysfunction is a common problem in patients with human immunodeficiency virus infection (HIV). We therefore evaluated the endocrine function in 31 male homosexual HIV-1-infected men: mean age 37 +/- 7.2 years (range 24-52). METHODS AND MATERIALS: Blood was obtained for baseline T3, T4, TSH, LH, FSH, prolactin, testosterone, ACTH and cortisol values. Endocrine function tests were performed as TRH, CRH, ACTH, LH-RH and HCG tests. RESULTS: Thyroid function: There was a temporarily increased TSH in 3 of 17 patients but normal levels for T3, T4 and fT4 (without thyroid antibodies). One patient showed signs of latent hyperthyroidism (no response in TRH test). Adrenocortical function: Two patients had adrenal insufficiency. They showed a normal baseline cortisol level, an elevated ACTH level and no increase in cortisol levels after stimulation with CRH. All other patients revealed normal responses on the CRH/ACTH tests. Gonadal function: 9 patients had elevated FSH levels (tubular insufficiency), 4 patients additionally had increased LH levels (hypergonadotropic hypogonadism). 5 patients showed signs of tertiary hypogonadism (low LH and testosterone, increase of LH after stimulation with LH-RH). CONCLUSION: In disorders of thyroid and adrenocortical function of primary or tertiary origin, a substitution of hormones should be taken into consideration.

Adrenal Cortex↗
PubMed2000

Inflammatory bowel disease in children and young adults: correlation of sonographic and clinical parameters during treatment.

OBJECTIVE: The objective of this study was to evaluate the sonographic findings of inflammatory bowel disease activity in children undergoing treatment. SUBJECTS AND METHODS: Eighty-eight sonograms were obtained of 23 bowel segments in 17 children and young adults (age range, 10-21 years; mean, 16 years) with new or recurrent inflammatory bowel disease. Sixteen segments were involved with Crohn's disease and seven with ulcerative colitis. Serial sonography (range, two to eight examinations; mean, four per segment) was performed while patients underwent treatment. Bowel wall thickness measurements and color and power Doppler sonography grading were recorded and compared with clinical data. RESULTS: All 17 patients had at least one abnormal bowel segment on initial sonography. The correlation was significant (p < 0.01). Agreement was 91% on direction of change over time between bowel wall thickness and Doppler grades, with 100% correlation between color and power Doppler sonography grades. In patients with Crohn's disease, the correlation was significant (p < 0.05) between bowel wall thickness and Doppler grades with two of seven and four of seven clinical parameters, respectively. In patients with ulcerative colitis, the correlation was significant (p < 0.05) between bowel wall thickness and Doppler sonography grades with four of seven and three of seven clinical parameters, respectively. The erythrocyte sedimentation rate correlated with all sonographic measurements in both patient groups. Combining bowel wall thickness and Doppler sonography, the percentage of agreement was significant in the direction of change, with five of seven clinical parameters in both patient groups. CONCLUSION: Gray-scale and color or power Doppler sonography can show changes in disease activity in children and young adults undergoing treatment for inflammatory bowel disease.

Adolescent↗
PubMed2000

The affinity of MCF7 breast cancer cells to hyaluronan substrates of different molecular weight and concentrations in an in vitro model.

The affinity of MCF7 breast cancer cells to hyaluronan (HA) was investigated in an in vitro model. The cells form a tightly adhering monolayer on native HA with a concentration of 5 mg/ml. On native HA at higher concentrations the cells reduce their adhesion to the substrate in favor of increased intercellular bonds, resulting in a cluster-like aggregate that tends to detach from the substrate. Aggregate formation is accomplished after 12 h incubation. The phenomenon is independent of the CD44 receptor. Degradation of native HA by hyaluronidase abolishes aggregate formation even at high HA concentrations in favor of formation of a firmly adhering monolayer. This model may help to understand tumor spread on HA tissue structures and may explain therapy successes with hyaluronidase in tumor patients.

Adenocarcinoma↗
PubMed1999

Enhanced oxygen delivery reverses anaerobic metabolic states in prolonged sandwich rat hepatocyte culture.

It must be assumed that current petri dish primary hepatocyte culture models do not supply sufficient amounts of oxygen and thus cause anaerobic metabolism of the cells. This is contrary to the physiologic state of the cells. In vivo the liver is a highly vascularized organ with a rather high blood flow rate of a mixture of arterial and venous blood. The aim of the present study was to show the oxygen dependence of primary rat hepatocytes in long-term culture and to define appropriate conditions that could allow hepatocytes to maintain tissue specific functions in an aerobic environment. To this purpose matrix overlaid hepatocytes were either cultured on gas-permeable (fluorinated hydrocarbon films) or gas-impermeable (polystyrene) supports at 10% and 20% ambient oxygen concentration (v/v), respectively. Tissue-specific functions were assessed by studying albumin and urea secretion as well as xenobiotic metabolism. The mRNA expression and catalytic activities of the cytoprotective antioxidant enzymes mitochondrial manganese superoxide dismutase (MnSOD), cytosolic copper and zinc superoxide dismutase, peroxisomal catalase, and cytosolic glutathione peroxidase were investigated to assess intracellular responses to the defined variations in oxygen supply. Hepatocytes could successfully be maintained at aerobic conditions in long-term culture on gas-permeable PTFE films. At 50% (10%, v/v) of currently used oxygen levels lactate accumulation was prevented, a plateau-like albumin secretion reestablished, urea secretion improved, and xenobiotic metabolism proceeded at physiological rates. mRNA expression of cytoprotective enzymes responded to the pericellular availability of oxygen and was most pronounced in the case of MnSOD. However, the biggest stress factor for the hepatocytes still appeared to be the isolation procedure, as mRNA expression and catalytic activities were most elevated shortly thereafter. In conclusion, this study clearly shows the oxygen dependence of primary rat hepatocytes in long-term culture and indicates means to establish appropriate conditions for the aerobic culture of primary rat sandwich hepatocytes with full maintenance of function. The long-term culture of hepatocytes on oxygenating supports at in vivo-like oxygen tensions therefore appears to be more physiologic and beneficial for the cells.

Aerobiosis↗
PubMed1999

Viability of cultured nerve grafts: An assessment of proliferation of Schwann cells and fibroblasts.

Previous studies demonstrated that the viability of nerve grafts had a positive effect on nerve regeneration, while the cold storage of nerve grafts obtained few viable cells at the later stage. The purpose of this study was to examine the cellular activities of Schwann cells and fibroblasts in cultured nerve grafts prior to transplantation. 2.5-cm long sciatic nerve grafts were harvested from 75 male Lewis rats. Two different media were utilized to culture the nerve grafts up to 3 weeks: Dulbecco's modified eagle medium (DMEM) only or DMEM supplemented with 2 microM forskolin and 10 microg/ml pituitary exact (mitogen medium for Schwann cells). In vivo predegenerated and normal nerve grafts were used as positive and negative controls, respectively. We employed a 5-bromo-2'-deoxyuridine (BrdU) incorporation method to evaluate the proliferating cells in the cultured nerve grafts. S-100 and vimentin immunostaining were used to estimate the presence of Schwann cells and fibroblasts in all nerve grafts at different intervals. The results showed that the proliferating cells increased progressively under culture conditions. The proliferating cells distributed evenly in small fascicles (average diameter 251 +/- 71.5 microm), whereas they appeared mainly in the margin of large fascicles (average diameter 624 +/- 87.3 microm). The mitogen medium stimulated Schwann cell multiplication more significantly in comparison with DMEM after 3 days of culture (P < 0.01), however, there were fewer fibroblasts present in the mitogen medium than in DMEM after 2 days of culture (P < 0.01). It is suggested that the viability of nerve grafts can be preserved under culture conditions. Furthermore, the cellular activity of the Schwann cells and fibroblasts in nerve grafts can be manipulated in in vitro Wallerian degeneration.

Animals↗
PubMed1999

Salvadora persica L.: hypolipidemic activity on experimental hypercholesterolemia in rat.

Stems of Salvadora persica are widely used as tooth cleaning sticks in Arabic countries and decoctions show hypocholesterolemic properties. The effects of prolonged administration of a lyophilized stem decoction of Salvadora persica were evaluated in diet-induced rat hypercholesterolemia. The preparation was administered for 15 and 30 days (by gavage at a dose of 500 mg/kg in an aqueous vehicle in a volume of 0.5 ml/100 g b.w.). Cholesterol, HDL, LDL and triglyceride plasma levels were assayed. The results showed that the S. persica decoction significantly lowered cholesterol and LDL plasma levels in rats, proving to be more active at 30 days of treatment. The systemic administration of Triton results in a rise in plasma cholesterol and triglyceride levels. The results obtained show that S. persica decoction was inactive at 18 hr after treatment, whereas at 27 hr, it was able to reduce cholesterol and LDL plasma levels. In all experiments HDL and triglycerides were unchanged.

Africa↗
PubMed1999

In vitro fertilization. Do short-term changes in estrogen levels produce increased fibrinolysis?

High estrogen levels have been implicated as a cause of thrombosis. Patients undergoing in vitro fertilization (IVF) present an opportunity to study isolated estrogen effects on the coagulation system, since hormonal manipulation is used to achieve varying estrogen concentrations. We evaluated the effect of estrogen levels on the fibrinolytic and clotting systems of 32 patients undergoing IVF from whom venous samples were obtained during a period of several weeks at baseline and retrieval times. Flow cytometric studies were performed to assay platelet activation. Hemostasis markers measured thrombin-antithrombin complexes (TAT), fibrinogen, plasmin-alpha 2-antiplasmin complexes (PAP), plasminogen activator inhibitor (PAI-1), and D-dimer. A significant decrease in PAI-1 and an increase in PAP were observed at high estrogen levels, suggesting an increase in fibrinolytic potential. However, the products of fibrinolysis, as measured by D-dimer levels, decreased at high estrogen levels. No changes were seen in platelet activation indicators or TAT levels. The fact that a decrease in products of fibrinolysis was seen at high estrogen levels despite concurrent changes in PAI-1 and PAP that normally accompany increased fibrinolysis may be due to alterations in the overall balance of the fibrinolytic system or to a delay in onset of fibrinolysis.

Estradiol↗