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Biomedical subjects

D Springer

Publications and source records attributed to D Springer.

At least 19 recordsLinked to original sources
PubMed2006

The influence of hormonal changes during menstrual cycle on serum adiponectin concentrations in healthy women.

Adiponectin is an adipocyte-derived hormone involved in the regulation of carbohydrate and lipid metabolism. Its concentrations are decreased in patients with obesity, type 2 diabetes and atherosclerosis and are higher in females than in males. Gender differences of adiponectin levels raise the possibility that sex hormones directly regulate its serum concentrations, which may in turn influence insulin sensitivity in different phases of the menstrual cycle. To test this hypothesis we measured serum adiponectin, estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone concentrations daily throughout the menstrual cycle in six healthy women. Mean adiponectin levels strongly positively correlated with serum cortisol concentrations [R=0.94286; p=0.0048 (Spearman correlation test)], but were not significantly related to other anthropometric, biochemical and hormonal characteristics of the subjects (BMI, blood glucose, insulin, testosterone, prolactin, cholesterol, HDL cholesterol, LDL cholesterol, triglycerides concentrations, or atherogenic index). Furthermore, no significant changes of serum adiponectin levels were found throughout the menstrual cycle. We conclude that changes in sex hormones during the menstrual cycle do not affect total circulating adiponectin levels in healthy women. Therefore, the differences in insulin sensitivity in various phases of the menstrual cycle are not due to changes of circulating adiponectin levels.

Adiponectin↗
PubMed2005

Identification of cytochrome P450 enzymes involved in the metabolism of 3',4'-methylenedioxy-alpha-pyrrolidinopropiophenone (MDPPP), a designer drug, in human liver microsomes.

The metabolism of 3',4'-methylenedioxy-a-pyrrolidinopropiophenone (MDPPP), a novel designer drug, to its demethylenated major metabolite 3',4'-dihydroxy-pyrrolidinopropiophenone (di-HO-PPP) was studied in pooled human liver microsomes (HLM) and in cDNA-expressed human hepatic cytochrome P450 (CYP) enzymes. CYP2C19 catalysed the demethylenation with apparent Km and Vmax values of 120.0+/-13.4 microM and 3.2+/-0.1 pmol/min/pmol CYP, respectively (mean+/-standard deviation). CYP2D6 catalysed the demethylenation with apparent Km and Vmax values of 13.5+/-1.5 microM and 1.3+/-0.1 pmol/min/pmol CYP, respectively. HLM exhibited a clear biphasic profile with an apparent Km,1 value of 7.6+/-9.0 and a Vmax,1 value of 11.1+/-3.6 pmol/min/mg protein, respectively. Percentages of intrinsic clearances of MDPPP by specific CYPs were calculated using the relative activity factor (RAF) approach with (S)-mephenytoin-4'-hydroxylation or bufuralol-1'-hydroxylation as index reactions for CYP2C19 or CYP2D6, respectively. MDPPP, di-HO-PPP and the standard 4'-methyl-pyrrolidinohexanophenone (MPHP) were separated and analysed by liquid chromatography-mass spectrometry in the selected-ion monitoring (SIM) mode. The CYP2D6-specific chemical inhibitor quinidine (3 microM) significantly (p<0.001) inhibited di-HO-PPP formation by 75.8%+/-1.7% (mean+/-standard error of the mean) in incubation mixtures with HLM and 2 microM MDPPP. It can be concluded from the data obtained from kinetic and inhibition studies that polymorphically expressed CYP2D6 and CYP2C19 are almost equally responsible for MDPPP demethylenation.

Cells, Cultured↗
PubMed2004

In vivo metabolism of the new designer drug 1-(4-methoxyphenyl)piperazine (MeOPP) in rat and identification of the human cytochrome P450 enzymes responsible for the major metabolic step.

1. The in vivo metabolism of 1-(4-methoxyphenyl)piperazine (MeOPP), a novel designer drug, was studied in male Wistar rats. 2. MeOPP was mainly O-demethylated to 1-(4-hydroxyphenyl)piperazine (4-HO-PP) in addition to degradation of the piperazine moiety. 3. O-demethylation, the major metabolic step, was studied with cDNA-expressed human hepatic cytochrome P450 (CYP) enzymes in pooled human liver microsomes (pHLM) and in single donor human liver microsomes with CYP2D6 poor metabolizer genotype (PM HLM). 4. CYP2D6 catalysed O-demethylation with apparent Km and Vmax values of 48.34 +/- 14.48 microM and 5.44 +/- 0.47 pmol min(-1) pmol(-1) CYP, respectively. pHLM catalysed the monitored reaction with an apparent Km = 204.80 +/- 51.81 microM and Vmax = 127.50 +/- 13.25 pmol min(-1) mg(-1) protein. 5. The CYP2D6-specific chemical inhibitor quinidine (1 and 3 microM) significantly inhibited 4-HO-PP formation by 71.9 +/- 4.8% and by 98.5% +/- 0.5%, respectively, in incubation mixtures with pHLM and 200 microM MeOPP. 6. O-demethylation was significantly lower in PM HLM compared with pHLM (70.6% +/- 7.2%). 7. These data suggest that polymorphically expressed CYP2D6 is the enzyme mainly responsible for MeOPP O-demethylation.

Algorithms↗
PubMed2003

Identification of cytochrome P450 enzymes involved in the metabolism of 4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), a designer drug, in human liver microsomes.

1. The metabolism of 4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), a novel designer drug, to its demethylated major metabolite 4'-hydroxy-pyrrolidinopropio-phenone (HO-PPP) was studied in pooled human liver microsomes (HLM) and in cDNA-expressed human hepatic cytochrome P450 (CYP) enzymes. 2. CYP2C19 catalysed the demethylation with apparent Km and Vmax values of 373.4 +/- 45.1 microM and 6.0 +/- 0.3 pmol min(-1) pmol(-1) CYP, respectively (mean +/- SD). Both CYP2D6 and HLM exhibited clear biphasic profiles with apparent K(m,1) values of 1.3 +/- 0.4 and 22.0 +/- 6.5 microM, respectively, and V(max,1) values of 1.1 +/- 0.1 pmol min(-1) pmol(-1) CYP and 169.1 +/- 20.5 pmol min(-1) mg(-1) protein, respectively. 3. Percentages of intrinsic clearances of MOPPP by particular CYPs were calculated using the relative activity factor (RAF) approach with (S)-mephenytoin-4'-hydroxylation or bufuralol-1'-hydroxylation as index reactions for CYP2C19 or CYP2D6, respectively. 4. MOPPP, HO-PPP and the standard 3',4'-methylenedioxy-pyrrolidinopropio-phenone (MDPPP) were separated and analysed by liquid chromatography-mass spectrometry in the selected-ion monitoring (SIM) mode. 5. The CYP2D6 specific chemical inhibitor quinidine (3 microM) significantly (p<0.0001) inhibited HO-PPP formation by 91.8 +/- 0.5% (mean +/- SEM) in incubation mixtures with HLM and 2 microM MOPPP. 6. It can be concluded from the data obtained from kinetic and inhibition studies that polymorphically expressed CYP2D6 is the enzyme mainly responsible for MOPPP demethylation.

Aryl Hydrocarbon Hydroxylases↗
PubMed2000

Optimization of extraction conditions for active components in Hypericum perforatum using response surface methodology.

Optimal conditions for extraction of Hypericum perforatum were determined using response surface methodology. A 3 x 4 x 4 full factorial design representing three extraction temperatures, four extraction times, and four solvent concentrations was executed. The overall extraction efficiency was defined by comparing either the total extractable material weight or the individual component peak area to the peak area of luteolin as internal standard. Of the tested variables, the extraction temperature most significantly affected extraction efficiency. Higher temperatures gave better extraction efficiencies, but high temperature also caused decomposition of hypericin. Within the test range, responses for most variables had local maxima. Optimum ranges of time and concentration for individual variables were overlaid. Considering all variables, optimum ranges for extraction time and extraction solvent concentration (percent ethanol in acetone) were 5.0-6.7 h and 44-74% at 23 degrees C, 5.4-6.9 h and 45-72% at 40 degrees C, and 5.3-5.9 h and 44-69% ethanol in acetone at 55 degrees C, respectively.

Hypericum↗
PubMed1991

Approaches to the C-B-A trisaccharide of dihydroaclacinomycin by extending the chain from either side.

Selective benzylation of L-fucal (1) under phase-transfer conditions gave the 3- and 4-monoethers 2 and 3, respectively. Two routes, the "tail" or the "head" addition are presented, both leading to the target molecule 9, a mimic of the C-B-A trisaccharide component of dihydroaclacinomycin. Addition of glycals 2 and 3 respectively, to the acetylated glycal (7) of amicetose used as glycosyl donor gave the disaccharide glycals 6 and 8. Alternatively, glucosylation of the 4-acetate (4) of 2 with the benzyl hex-2-enopyranoside derivative 10 gave the disaccharide derivative 11. In the first case, the final glycosylation step involves the addition of 10 to disaccharide glycal 8. In the second procedure, the disaccharide alcohol 12 is obtained by O-deacetylation of 11, and serves as the glycosyl acceptor for glycal derivative 7 to give the C-B-a precursor trisaccharide derivative.

Aclarubicin↗
PubMed1991

Lack of specificity of monoclonal antibody B72.3 in distinguishing chronic pancreatitis from pancreatic adenocarcinoma.

Making the morphologic distinction between chronic pancreatitis and pancreatic adenocarcinoma is a diagnostic challenge in small biopsy specimens and fine-needle aspiration samples. It has been suggested that immunohistochemical evaluation for the tumor-associated glycoprotein-72 antigen recognized by the monoclonal antibody B72.3 may be helpful in this setting. Formalin-fixed, routinely processed, paraffin-embedded tissue from 29 known cases of chronic pancreatitis and 31 cases of pancreatic adenocarcinoma were evaluated for reactivity with monoclonal antibody B72.3 using a standard avidin-biotin complex technique. Positive staining was seen in 26 of 31 adenocarcinomas (84%) and in 6 of 29 cases (21%) of chronic pancreatitis. Although monoclonal antibody B72.3 is more commonly reactive with pancreatic adenocarcinoma than with chronic pancreatitis, too many cases of chronic pancreatitis are reactive with this antibody for it to be useful as a diagnostic adjunct.

Adenocarcinoma↗
PubMed1989

Comparison of disc space heights after anterior lumbar interbody fusion.

Thirty-one consecutive patients underwent anterior interbody fusion of 40 levels of the lumbar spine using autogenous, autologous, or mixed iliac crest graft. Each patient's disc space height was measured preoperatively, immediately postoperatively, and an average of 29 months postoperatively. The immediate postoperative radiograph demonstrated an average increase in disc space height of 89%, or 9.5 mm for each operated level. The late radiographic evaluation, from 7 to 54 months postoperatively, showed an average decrease of 1%, or 0.1 mm for each level. At late follow-up, no correlation could be found between the time from the operation and disc space height. One hundred percent of patients developed disc space height decreases during the postoperative period, with 46% of levels being narrower than their preoperative height at last follow-up. Loss of distraction is a normal postoperative occurrence of the procedure. Disc space distraction is temporary with anterior interbody fusion.

Adult↗
PubMed1988

Rapid diagnostic test for ocular adenovirus.

A new, direct, enzyme immunoassay test (Adenoclone, Cambridge BioScience, Hopkinton, MA) was evaluated for the rapid diagnosis of ocular adenovirus infections. In 36 culture-proven cases of adenovirus ocular infection, direct Adenoclone testing of conjunctival swabs was positive in 24 of 31 patients (77%) tested within 1 week of onset of symptoms, and in one of five patients (20%) who presented after 1 week (P less than 0.02). Overall sensitivity was 69%, whereas specificity was 100%. The authors conclude that a positive Adenoclone test is reliable in the rapid diagnosis of early adenovirus ocular infections.

Adenoviridae Infections↗
PubMed1977

[Spontaneous infection of marmoset-monkeys (Sanguinus oedipus) with a Trypanosoma cruzi-like-strain, Springer 1975. Isolation and identification (author's transl)].

A Trypanosoma cruzi-like strain was isolated from marmoset monkeys originating from Columbia. The frequency of affected monkeys was up to 32.7%. The parasite density was 10-40 trypomastigote forms per mililiter. Monkeys, rats, mice and other small Rodentia were found to be susceptible. Clinical symptoms or histopathological findings could not be acertained with these trypanosomes even after a 2 1/2 year observation period. The strain behaved as an apathogen in experimental animals. The parasitaemia in animals was sparse (1-10 trypanosomes/ml) and without any conspicuous periodic fluctuations. Trypanosomes could be detected microscopically up to 2 1/2 years after infection in the blood of infected animals. With a positive blood finding, the blood passage could be carried out in animals with regularity. The serum from infected reacted positively in Chagas Latex test as well as in Chagas CFT. The trypomastigote forms injected into cultures of human embryonal thyroid gland and in cells of other origin, showed higher or lower multiplication with a marked cytopathogenic effect between the 9th and 11th day post infection, depending on the type of tissue culture. There was a cyclical development in Rhodnius prolixus or Triatoma infestans. The so-called metacyclic or trypomastigote forms from the faeces of Reduviidae or from tissue culture could again infect animals.

Animals↗
PubMed1975

Effects of hypothalamic knife cuts on the ingestive responses to glucose and insulin.

Parasagittal knife cuts through the perifornical hypothalamus either medial or lateral to the fornix produced hyperphagia and obesity and altered the rat's ingestive responses to dilute glucose solutions. The lateral knife cut rats drank less dilute glucose solution under both nondeprived and food deprived conditions and displayed less of a feeding suppressive response to glucose ingestion compared to controls. The lateral cut rats were also deficient in their feeding response to insulin-induced hypoglycemia, although their altered sensitivity to glucose and insulin did not appear to be causally related. The medial knife cuts decreased the responsivity to glucose, but less so than the lateral cuts, and did not alter the ingestive response to insulin. Both the medial and lateral knife cuts did not appear to change the rat's responsivity to concentrated blucose solutions. The neuroanatomical and functional nature of the disorder responsible for these effects and its relationship to the hyper-phagia-obesity syndrome are discussed.

Animals↗