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Biomedical subjects

A Schroeder

Publications and source records attributed to A Schroeder.

At least 19 recordsLinked to original sources

Recombinant luteinizing hormone supplementation to recombinant follicle-stimulating hormone induced ovarian hyperstimulation in the GnRH-antagonist multiple-dose protocol.

BACKGROUND: Suppression of endogenous LH production by mid-follicular phase GnRH-antagonist administration in controlled ovarian hyperstimulation protocol using recombinant (rec) FSH preparations void of LH activity may potentially affect ovarian response and the outcome of IVF treatment. The present study prospectively assessed the effect of using a combination of recFSH and recLH on ovarian stimulation parameters and treatment outcome in a fixed GnRH-antagonist multiple dose protocol. METHODS: 127 infertile patients with an indication for IVF or ICSI were recruited and randomized (using sealed envelopes) to receive a starting dose of either 150 IU recFSH (follitropin alpha) or 150 IU recFSH plus 75 IU recLH (lutropin alpha) for ovarian hyperstimulation. GnRH-antagonist (Cetrorelix) 0.25 mg was administered daily from stimulation day 6 onwards up to and including the day of the administration of recombinant HCG (chorion gonadotropin alpha). Gonadotropin dose adjustments were allowed from stimulation day 6 onwards, HCG was administered as soon as three follicles > or =18 mm were present. The primary outcome parameter was treatment duration until administration of HCG. RESULTS: Exogenous LH did not shorten the time necessary to reach ovulation induction criteria. Serum estradiol (E(2)) and LH levels were significantly higher on the day of HCG administration in the recLH-supplemented group (1924.7 +/- 1256.4 vs 1488.3 +/- 824.0 pg/ml, P < 0.03), and 2.1 +/- 1.4 vs 1.4 +/- 1.5 IU/l, P < 0.01, respectively). CONCLUSIONS: Except for higher E(2) and LH levels on the day of HCG administration, no positive trend in favour of additional LH was found as defined by treatment outcome parameters.

Adult↗

Sleep disordered breathing in the elderly: comparison of women and men.

The prevalence of obstructive sleep apnea syndrome in patients up to the age of 60 is known to be two times higher in men then in women. Hormonal changes during menopause might underlie changes in this relationship in the elderly. This study was designed to detect differences in the type and frequency of sleep-disordered breathing between women and men over the age of 65 years, having the same body mass index. The study was conducted using a matched-pair approach consisting of a sample population of 40 pairs of patients over the age of 65. All patients met the following exclusion criteria: age below 65, heart failure, chronic obstructive lung disease. Polygraphy was conducted by means of a portable recorder. All measured indices were higher in men than in women. The apnea index was 2.8 +/-4.1 in men and 0.6 +/-1.4 in women. The apnea/hypopnea index was 10.2 +/-11.4 and 4.8 +/-3.9, respectively. These differences were significant (P<0.05). Significant differences also were observed when central (men 8.1 +/-13.1, women 3.1 +/-8.2), mixed (men 5.1 +/-11.4, women 0.4 +/-1.3), and obstructive (women men 8.6 +/-20.1, 1.0 +/-4.3) apnea indices were compared. In conclusion, the study demonstrates that elderly patients showed gender-dependent differences in the type and frequency of sleep-related breathing disorders. Men suffered from all kinds of apnea more frequently than women.

Aged↗

3D evaluation of myocardial edema: experimental study on 22 pigs using magnetic resonance and tissue analysis.

BACKGROUND: Myocardial edema (ME) adversely affects ventricular function. Thus, we performed an animal study to demonstrate (1) 3D-ME using magnetic resonance imaging (MRI), which can show ME depending on myocardial location, (2) type of cardioplegic solution, and (3) quantification tools. METHODS: Pig hearts (n = 22) were perfused using Bretschneider's solution (BRET, n = 8), butanedionemonoxime (BDM, n=8), or no cardioplegia as controls (CTRL, n = 6). Hearts underwent MRI (T(1)-inversion recovery). Myocardial water content (MWC, reference method) was determined from left ventricle anterior, posterior (PW), lateral wall, interventricular septum, papillary muscle, right ventricle wall. Images underwent 3D reconstruction using ray-tracing. Gray-value analysis was performed on "virtual" samples. For statistical analysis, ANOVA, Student's t-test, and the Student-Newman-Keuls test were used. RESULTS: (1) ME was induced (p < 0.0001 vs. control). Localization differed in MWC, p = 0.003 (BRET), p = 0.023 (BDM), highest at PW (p < 0.01). (2) Differences between the cardioplegia groups were not significant. (3) "Virtual" samples showed equal distribution (BRET: p = 0.007, BDM: p = 0.003), highest at PW (p < 0.01). CONCLUSIONS: We validated 3D assessment of induced ME in pig hearts using MRI. The method may therefore become an exact tool in monitoring cardioplegia.

Animals↗

Titanium containing amorphous hydrogenated carbon films (a-C: H/Ti): surface analysis and evaluation of cellular reactions using bone marrow cell cultures in vitro.

Amorphous hydrogenated carbon (a-C : H) coatings, also called diamond-like carbon (DLC), have many properties required for a protective coating material in biomedical applications. The purpose of this study is to evaluate a new surface coating for bone-related implants by combining the hardness and inertness of a-C : H films with the biological acceptance of titanium. For this purpose, different amounts of titanium were incorporated into a-C : H films by a combined radio frequency (rf) and magnetron sputtering set-up. The X-ray photoelectron spectroscopy (XPS) of air-exposed a-C : H/titanium (a-C : H/Ti) films revealed that the films were composed of TiO2 and TiC embedded in and connected to an a-C : H matrix. Cell culture tests using primary adult rat bone marrow cell cultures (BMC) were performed to determine effects on cell number and on osteoblast and osteoclast differentiation. By adding titanium to the carbon matrix, cellular reactions such as increased proliferation and reduced osteoclast-like cell activity could be obtained, while these reactions were not seen on pure a-C : H films and on glass control samples. In summary, a-C : H/Ti could be a valuable coating for bone implants, by supporting bone cell proliferation while reducing osteoclast-like cell activation.

Analysis of Variance↗

Effect of calcium channel blockers alone and in combination with antiglaucoma medications on intraocular pressure in the primate eye.

PURPOSE: To determine the effect of representative members from six classes of calcium channel blockers on intraocular pressure in the primate eye. Other antiglaucoma medications were administered with verapamil to determine their combined effect on intraocular pressure. METHODS: Six healthy cynomolgus monkeys were anesthetized, and baseline intraocular pressure was measured. Drug-containing solution (50 microL) was instilled in one eye and intraocular pressure was measured in both eyes 90 minutes later. RESULTS: All classes of calcium channel blockers significantly lowered intraocular pressure in the treated eye. The percent reduction in intraocular pressure compared with the baseline pressure was 10% for verapamil (P < 0.002), 18% for nifedipine (P < 0.001), 15% for diltiazem (P < 0.001), 17% for flunarizine (P < 0.001), 19% for prenylamine (P < 0.001), and 6% for perhexiline (P < 0.01). In the fellow eye, a significant reduction in intraocular pressure was also seen with all calcium channel blockers except perhexiline, which suggested a crossover effect. In contrast, neither vehicle treated nor contralateral eyes showed a lowering of intraocular pressure when tested under the same conditions. In the treated eye, 0.5% timolol (P < 0.01) and 0.05% clonidine (P < 0.02) combined with 0.25% verapamil each appeared to produce an additive effect, with a significantly greater pressure-lowering effect than either agent alone. In addition, 0.005% pilocarpine (P < 0.001) and 0.00125% demecarium (P < 0.01) combined with 0.25% verapamil each appeared to produce a synergistic effect, with a significantly greater reduction in intraocular pressure than both agents combined. CONCLUSIONS: Topical calcium channel blockers and combinations of verapamil with antiglaucoma medications may provide a useful alternative for reducing intraocular pressure in patients with ocular hypertension or primary open-angle glaucoma.

Animals↗

Ethanol stimulates glucose uptake and translocation of GLUT-4 in H9c2 myotubes via a Ca(2+)-dependent mechanism.

Short-term exposure to ethanol impairs glucose homeostasis, but the effects of ethanol on individual components of the glucose disposal pathway are not known. To understand the mechanisms by which ethanol disrupts glucose homeostasis, we have investigated the direct effects of ethanol on glucose uptake and translocation of GLUT-4 in H9c2 myotubes. Short-term treatment with 12.5-50 mM ethanol increased uptake of 2-deoxyglucose by 1.8-fold in differentiated myotubes. Pretreatment of H9c2 myotubes with 100 nM wortmannin, an inhibitor of phosphatidylinositol 3-kinase, had no effect on ethanol-induced increases in 2-deoxyglucose uptake. In contrast, preincubation with 25 microM dantrolene, an inhibitor of Ca(2+) release from the sarcoplasmic reticulum, blocked the stimulation of 2-deoxyglucose uptake by ethanol. Increased 2-deoxyglucose uptake after ethanol treatment was associated with a decrease in small intracellular GLUT-4 vesicles and an increase in GLUT-4 localized at the cell surface. In contrast, ethanol had no effect on the quantity of GLUT-1 and GLUT-3 at the plasma membrane. These data demonstrate that physiologically relevant concentrations of ethanol disrupt the trafficking of GLUT-4 in H9c2 myotubes resulting in translocation of GLUT-4 to the plasma membrane and increased glucose uptake.

Adipocytes↗

Expression of adenylate cyclase subtypes II and IV in the human outflow pathway.

PURPOSE: It has been demonstrated that low doses of pilocarpine and other muscarinics substantially increase outflow facility in the isolated human outflow system devoid of ciliary muscle. These cholinergic-induced facility responses were thought possibly to be due to elevation of cAMP as a result of the presence of adenylate cyclases II (AC-II) and IV (AC-IV). Therefore, whether these isoforms are present in outflow tissues was examined. METHODS: Human anterior segments were perfused with carbachol (10(-9)-10(-5) M), and outflow facility and cAMP levels in the perfusate were measured simultaneously. Isolated trabecular meshwork (TM) were incubated with carbachol (10(-7) M), and the subsequent changes in cAMP were measured by radioimmunoassay. AC-II and AC-IV were characterized in ocular tissue with reverse transcription-polymerase chain reaction and in situ hybridization. RESULTS: Outflow facility increased, in a dose-dependent manner, by 10%, 16%, and 27% in response to 10(-9), 10(-7), and 10(-5) M carbachol, respectively. Similarly, cAMP increased by 9%, 70%, and 210% in response to 10(-9), 10(-7), and 10(-5) M carbachol, respectively. In addition, cAMP levels significantly increased by 39% in isolated TM strips incubated with 10(-7) M carbachol. AC-II was detected in most normal tissue examined, but not in any cultured cell lines or any glaucomatous tissue. AC-IV was also widely expressed in most normal tissues, faintly detected in some glaucoma tissue, but not detected in most cultured cells. CONCLUSIONS: The presence of AC-II and AC-IV in outflow tissues supports the hypothesis that cholinergics may indeed exert an effect on outflow facility, mediated by cAMP, which is independent of muscle contraction.

Adenylyl Cyclases↗

Direct effects of muscarinic agents on the outflow pathways in human eyes.

PURPOSE: Recent studies demonstrating the presence of muscarinic receptors and contractile-like cells in the trabecular meshwork tissue and/or cell cultures from human eyes suggest the possibility that there may be a direct effect of muscarinic agonists on outflow facility. The present studies were conducted to determine whether muscarinic agonists could change outflow facility in perfused human ocular anterior segments, which lack an intact ciliary muscle. METHODS: Human eyes were dissected and perfused according to previously described methods. A steady state baseline facility was established for 90 minutes, after which up to four sequential concentrations ranging from 10(-9) to 10(-3) M of pilocarpine, aceclidine, or carbachol were added to the perfusion medium. In other studies, 10(-6) M atropine was perfused alone followed by 10(-7) M carbachol with 10(-6) M atropine, whereas fellow control eyes received carbachol alone. Outflow facility was measured for 60 minutes after each drug addition. The outflow facility measurement in each eye after drug administration was compared with the baseline measurement. RESULTS: Outflow facility increased from baseline facility in eyes treated with pilocarpine, aceclidine, or carbachol at lower concentrations (10(-9) to 10(-6) M) but remained unchanged at higher concentrations (10(-4) to 10(-2) M). The effects of carbachol at 10(-7) M were completely blocked by atropine. CONCLUSIONS: Muscarinic agonists increase outflow facility in human eyes by a direct stimulation of the outflow tissues in the absence of an intact ciliary muscle. This effect is biphasic, occurring at concentrations of 10(-6) M and lower with no effect at higher concentrations.

Aged↗

Toxicity of 4-chloroaniline in early life stages of zebrafish (Danio rerio): II. Cytopathology and regeneration of liver and gills after prolonged exposure to waterborne 4-chloroaniline.

Ultrastructural alterations in liver and gills of embryonic and larval zebrafish (Danio rerio) following prolonged exposure to waterborne 0.05, 0.5, and 5 mg/L 4-chloroaniline for up to 31 days as well as after a 14-day regeneration period were investigated by means of light and electron microscopy. Acute toxicity was also tested at 25 and 50 mg/L. Survival of zebrafish embryos and larvae was only impaired from 25 mg/L 4-chloroaniline, but-after a transient stimulation following exposure to 0.5 mg/L-4-chloroaniline hatching was retarded after exposure to >/=5 mg/L, and fish displayed increasing rates of abnormal development and pigmentation. In contrast, hepatocytes displayed a time- and dose-dependent response from 0.05 mg/L 4-chloroaniline, including changes in nuclei, mitochondria, peroxisomes, endoplasmic reticulum, Golgi fields, lysosomes, and hepatic glycogen and lipid stores, as well as invasion of macrophages. In gills, dose-dependent effects were evident from 0.5 mg/L 4-chloroaniline and included deformation of secondary lamellae due to vacuolization and desquamation of respiratory epithelial cells in conjunction with dilation of intercellular spaces. Respiratory epithelial cells displayed progressive mitochondrial changes, induction of cytoplasmic myelinated structures, augmentation of lysosomes, and modifications of Golgi fields. Erythrocytes were severely deformed. A 14-day regeneration period was sufficient for almost complete recovery of pathological symptoms in both liver and gills. Only minor volumetric changes in hepatocellular organelles and a limited number of myelinated bodies, lysosomes, and cytoplasmic vacuoles were reminiscent of prior 4-chloroaniline exposure. In both qualitative and quantitative terms, most effects in hepatocytes after exposure of embryonic and larval zebrafish to waterborne 4-chloroaniline are comparable to the reaction of hepatocytes in adult zebrafish liver after prolonged sublethal exposure as well as in larval zebrafish after microinjection. Morphological changes in erythrocytes indicate disturbance of respiration as an additional mode of action of 4-chloroaniline.

Aniline Compounds↗

Aortobifemoral prosthetic infection treated by cryopreserved arterial homografts of the European Homograft Bank.

The excision of an infected aortobifemoral Dacron graft 9 years after implantation and bilateral axillofemoral Dacron bypass reconstruction led to reinfection of the extra-anatomic bypass grafts. A new aortobifemoral reconstruction was performed using cryopreserved homografts delivered by the European Homograft Bank in Brussels and both axillo-femoral prostheses were removed. No signs of infection and no alterations of the homografts can be detected 3 years later.

Aorta, Abdominal↗

Effect of continuous administration of a cholinergic agonist on [3H]4-DAMP binding and m3 mRNA expression in cultured human ciliary muscle cells.

It is well known that chronic topical administration of cholinergic agonists results in a subsensitization in ciliary muscle-mediated increases in outflow facility and accommodation in monkey eyes in vivo. These physiologic changes are apparently mediated by the M3 subtype receptor. However, the nature of this subsensitization remains unclear. This study investigated the effect of the continuous presence of carbachol, a muscarinic agonist, on the expression of the muscarinic receptor subtype m3 and the binding of [3H]4-DAMP in cultured human ciliary muscle cells (H7CM). The H7CM cell line, derived from the ciliary muscle of a one-day-old human infant, was used in this study. Confluent monolayers were treated individually with 1 mM carbachol for 2, 6, 24 and 48 hours. The level of mRNA encoding muscarinic receptor subtype m3 was measured by RNase protection. For confirmation, a receptor binding assay was done using [3H]4-DAMP, a radioligand selective for M3 subtype receptors. At each timepoint, results were compared with untreated controls. Treatment with carbachol resulted in a down regulation ranging from 23.4% to 34.8% of m3 mRNA expression at all time points. All [3H]4-DAMP binding assay results also decreased, ranging from 24.5% to 31.0%.

Carbachol↗

Polyspecific substrate uptake by the hepatic organic anion transporter Oatp1 in stably transfected CHO cells.

The rat liver organic anion transporting polypeptide (Oatp1) has been extensively characterized mainly in the Xenopus laevis expression system as a polyspecific carrier transporting organic anions (bile salts), neutral compounds, and even organic cations. In this study, we extended this characterization using a mammalian expression system and confirm the basolateral hepatic expression of Oatp1 with a new antibody. Besides sulfobromophthalein [Michaelis-Menten constant (Km) of approximately 3 microM], taurocholate (Km of approximately 32 microM), and estradiol- 17beta-glucuronide (Km of approximately 4 microM), substrates previously shown to be transported by Oatp1 in transfected HeLa cells, we determined the kinetic parameters for cholate (Km of approximately 54 microM), glycocholate (Km of approximately 54 microM), estrone-3-sulfate (Km of approximately 11 microM), CRC-220 (Km of approximately 57 microM), ouabain (Km of approximately 3,000 microM), and ochratoxin A (Km of approximately 29 microM) in stably transfected Chinese hamster ovary (CHO) cells. In addition, three new substrates, taurochenodeoxycholate (Km of approximately 7 microM), tauroursodeoxycholate (Km of approximately 13 microM), and dehydroepiandrosterone sulfate (Km of approximately 5 microM), were also investigated. The results establish the polyspecific nature of Oatp1 in a mammalian expression system and definitely identify conjugated dihydroxy bile salts and steroid conjugates as high-affinity endogenous substrates of Oatp1.

Animals↗

Effects of Na-K-2Cl cotransport regulators on outflow facility in calf and human eyes in vitro.

PURPOSE: Cultured human trabecular meshwork (TM) cells possess substantial Na-K-Cl activity, which is involved in the regulation of TM cell volume. The hypothesis in the present study was that drugs that affect the cotransporter might alter aqueous humor outflow facility (C) in the intact eye. The effects of agents and conditions known to modulate Na-K-CI cotransport activity and/or TM cell volume on C in perfused anterior segments were investigated. METHODS: Human and calf eyes were dissected and perfused, and C was determined according to standard published methods. Perfusates with modified osmolarity were used to cause alterations in TM cell volume. Cl-free perfusate and/or bumetanide (10(-5) M) was used to inhibit Na-K-Cl cotransport activity, and vasopressin (10(-7) M, 10(-8) M) was used to stimulate cotransport activity. RESULTS: In human eyes, hypo-osmotic perfusate decreased C 12%, whereas hyper-osmotic perfusate increased C 44%. These changes lasted approximately 30 minutes, after which C began to normalize. Inhibition of Na-K-Cl cotransport using Cl-free medium or bumetanide resulted in facility increases of 27% and 22%, respectively. There was an additive increase in C with bumetanide plus Cl-free media. Stimulating Na-K-Cl cotransport with 10(-8)M and 10(-7)M vasopressin resulted in 28% and 35% decreases in C, respectively. The results were similar in calf eyes: Cl-free medium or bumetanide resulted in 41% and 52% increases in C, whereas 10(-8) M and 10(-7) M vasopressin resulted in 14% and 19% decreases in C, respectively. CONCLUSIONS: Modulation of Na-K-Cl cotransport results in changes in C that may be mediated in part by cell volume changes.

Aged↗

End-to-end versus end-to-side arterial anastomosis patency in microvascular surgery.

The patency rates of microsurgical end-to-end and end-to-side anastomosis in the rat carotid artery were studied. Seventy end-to-end and seventy end-to-side arterial anastomoses, using 10-0 nylon interrupted sutures, were performed on 140 Sprague-Dawley rats. Findings indicated 100% patency in end-to-end as well as end-to-side immediately and 1 week post-anastomosis. This investigation suggests that there is no significant advantage between the methods studied based on vessel patency alone. The decision to perform an end-to-end vs. an end-to-side arterial anastomosis should be based upon the clinical circumstances encountered, since no significant difference in patency rates exists.

Anastomosis, Surgical↗

Substrate specificity of the rat liver Na(+)-bile salt cotransporter in Xenopus laevis oocytes and in CHO cells.

It has been proposed that the hepatocellular Na(+)-dependent bile salt uptake system exhibits a broad substrate specificity in intact hepatocytes. In contrast, recent expression studies in mammalian cell lines have suggested that the cloned rat liver Na(+)-taurocholate cotransporting polypeptide (Ntcp) may transport only taurocholate. To characterize its substrate specificity Ntcp was stably transfected into Chinese hamster ovary (CHO) cells. These cells exhibited saturable Na(+)-dependent uptake of [3H]taurocholate [Michaelis constant (K(m)) of approximately 34 microM] that was strongly inhibited by all major bile salts, estrone 3-sulfate, bumetanide, and cyclosporin A. Ntcp cRNA-injected Xenopus laevis oocytes and the transfected CHO cells exhibited saturable Na(+)-dependent uptake of [3H]taurochenodeoxycholate (Km of approximately 5 microM), [3H]tauroursodeoxycholate (Km of approximately 14 microM), and [14C]glycocholate (Km of approximately 27 microM). After induction of gene expression by sodium butyrate, Na(+)-dependent transport of [3H]estrone 3-sulfate (Km of approximately 27 microM) could also be detected in the transfected CHO cells. However, there was no detectable Na(+)-dependent uptake of [3H]bumetanide or [3H]cyclosporin A. These results show that the cloned Ntcp can mediate Na(+)-dependent uptake of all physiological bile salts as well as of the steroid conjugate estrone 3-sulfate. Hence, Ntcp is a multispecific transporter with preference for bile salts and other anionic steroidal compounds.

Animals↗

Substrate specificity of sinusoidal bile acid and organic anion uptake systems in rat and human liver.

The Na+-dependent bile salt uptake systems Ntcp (rodents) and NTCP (human), and the Na+-independent organic anion transporters oatpl (rat) and OATP (human) mediate sinusoidal uptake of a variety of amphipathic organic compounds into hepatocytes. Their properties indicate that an overall hepatic clearance of albumin-bound compounds is mediated by a limited number of multispecific transporters with partially overlapping substrate specificities.

Animals↗