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1.
BMC Psychiatry ; 18(1): 382, 2018 12 06.
Article in English | MEDLINE | ID: mdl-30522460

ABSTRACT

BACKGROUND: The number of asylum seekers, refugees and internally displaced people worldwide has increased dramatically over the past 5 years. Many countries are continuing to resort to detaining asylum seekers and other migrants, despite concerns that this may be harmful. In light of the considerable body of recent research, this review aims to update and expand on a 2009 systematic review on the mental health consequences of detention on adult, adolescent and child immigration detainees, which found (on the basis on 9 studies) that there was consistent evidence that immigration detention had adverse effects on mental health. METHODS: Three databases were searched using key terms relating to immigration detention and mental health. Electronic searches were supplemented by reference screening. Studies were included if they were quantitative, included individuals detained for immigration purposes, reported on mental health problems and were published in peer-reviewed journals. Two reviewers independently screened papers for eligibility, and a further two reviewers completed quality appraisals for included studies. RESULTS: Twenty- six studies (21 of which were not included in the 2009 review) reporting on a total of 2099 participants were included in the review. Overall, these studies indicated that adults, adolescents and children experienced high levels of mental health problems. Anxiety, depression and post-traumatic stress disorder were most commonly reported both during and following detention. Higher symptom scores were found in detained compared to non-detained refugees. In addition (and more clearly than was evident in 2009), detention duration was positively associated with severity of mental symptoms. Greater trauma exposure prior to detention was also associated with symptom severity. CONCLUSIONS: The literature base reviewed in this paper consistently demonstrated severe mental health consequences amongst detainees across a wide range of settings and jurisdictions. There is a pressing need for the proper consideration of mental health and consequent risk of detention-related harm in decisions surrounding detention as well as for improved care for individuals within detention facilities. Recommendations based on these findings are presented, including increased focus on the identification of vulnerability and on minimising the duration of detention.


Subject(s)
Emigration and Immigration , Mental Health , Refugees/psychology , Trauma and Stressor Related Disorders/etiology , Humans
3.
J Biomed Mater Res A ; 83(4): 1154-1164, 2007 Dec 15.
Article in English | MEDLINE | ID: mdl-17595023

ABSTRACT

Reconstruction of bone defects in the field of craniomaxillofacial surgery is a relevant problem. In regenerative medicine, autologous bone is not available sufficiently. The full replacement of autologous bone grafts is required. A promising research field is the bone engineering. Especially the application of rapid prototyping (RP) enables new perspectives concerning the scaffold design. The aim of the study was to compare scaffolds produced by RP-technology (native and plasma-coated PLGA-scaffolds) with conventionally produced scaffolds (agar plates with hydroxyapatite and hyaluronic acid coated agar plates with hydroxyapatite) relating to proliferation, adhesion, and morphology of osteoblasts to get knowledge about the application potential of such 3D-manufactured matrices for bone engineering. TissueFoil E served as reference. To compare the scaffolds, 12 ovine and 12 human osteoblast-like cell cultures of the skull were used. Results were obtained by EZ4U, scanning electron microscopy, and light microscopy. The highest cell proliferation rate of human osteoblast-like cells was measured on TissueFoil E followed by plasma-coated PLGA-scaffolds and uncoated PLGA-scaffolds, whereas of ovine osteoblast-like cells on plasma-coated PLGA-scaffolds followed by TissueFoil E and uncoated PLGA-scaffolds. Human and ovine osteoblast-like cells on coated and uncoated agar plates had significant lower proliferation rates compared with TissueFoil E and PLGA-scaffolds. These results showed the potential of RP in the field of bone engineering. Mechanical properties of such scaffolds and in vivo studies should be investigated to examine if the scaffolds hold up the pressure it will undergo long enough to allow regrowth of bone and to examine the revascularization.


Subject(s)
Bone and Bones , Cell Proliferation , Osteoblasts/cytology , Alkaline Phosphatase/metabolism , Animals , Collagen Type I/metabolism , Humans , Microscopy, Electron, Scanning , Osteoblasts/enzymology , Osteoblasts/metabolism , Sheep , Tissue Engineering
4.
Int J Oral Maxillofac Surg ; 36(1): 45-53, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17184974

ABSTRACT

The aim of this study was to evaluate the topographical anatomy of the human orbital floor for the production of prefabricated implants on the basis of computer tomography data. A database of 279 CT scans of Caucasian patients without traumatic deformation of the midface was analysed. 3D-image segmentation of the midfacial skeleton was performed using a computer-assisted protocol. A virtual plane (50 x 50 mm (2)) was constructed using defined landmarks above the orbital floor. An automated procedure was used to measure the distance between the orbital floor and the constructed plane at 400 distinct points. A mathematical algorithm was used to analyse the data, and to calculate a map of the orbital floor. Statistical analysis of the data revealed that orbital floor topography could be classified as distinct clusters. There were 12 variations of orbital floor anatomy: three unique patterns of the orbital floor for the right orbit and three corresponding patterns for the left side, all of which varied between the sexes. The 12 patterns were constructed with a statistical confidence interval of 1.36+/-0.6mm.


Subject(s)
Computer Simulation , Orbit/anatomy & histology , Orbit/diagnostic imaging , Orbital Implants , Adult , Algorithms , Databases, Factual , Female , Humans , Imaging, Three-Dimensional/methods , Male , Tomography, X-Ray Computed
5.
Br J Oral Maxillofac Surg ; 45(4): 326-7, 2007 Jun.
Article in English | MEDLINE | ID: mdl-16377040

ABSTRACT

Teratomas are benign tumors containing cells from ectodermal, mesodermal and endodermal layers. They occur in about 1 in every 4000 births and most commonly in the sacrococcygeal region, followed by the ovaries. Congenital epignathus teratomas are rare embryological neoplasms localised in the region of head and neck. An epignathus is found in approximately 1:35,000 to 1:200,000 live births. This accounts for 2-9% of all teratomas. Size and location of the neoplasm in the oronasopharynx is variable. Teratomas are partly undiagnosed at the time of birth. They may exist with an intracranial extension or as small polyps. Large epignathi can lead to difficult management during and after birth. The case of a newborn girl with a combination of an epignathus and a cleft palate is described. The epignathus presented as a huge mass extending out of the mouth of the infant girl. On the day of birth debulking of the extraoral portion of the tumor, followed by intraoral exstirpation, was performed. The results of the histologic examination indicated a congenital epignathus. Six months later a recurrence was found.


Subject(s)
Cleft Palate/etiology , Skull Base Neoplasms/congenital , Teratoma/congenital , Female , Follow-Up Studies , Humans , Infant, Newborn , Neoplasm Recurrence, Local/pathology , Nose Neoplasms/congenital , Nose Neoplasms/pathology , Teratoma/pathology
6.
Int J Oral Maxillofac Surg ; 35(11): 990-5, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17049812

ABSTRACT

The purpose of this investigation is to present the results using preoperatively-formed titanium mesh implants for a true-to-original primary repair of extensive orbital floor and medial wall fractures. Individually preformed implants were used to repair extensive orbital floor injuries in 19 patients at the University Hospital, Freiburg. The form of the orbital floor and walls was analysed by preoperative diagnostic CT scan data. The form of the virtual reconstructed orbit was transformed into a model of the orbital cavity by a template machine. Postoperative imaging by or CT scan verified the exact 3D reconstruction of the orbital cavity 'true to original'. None of the patients demonstrated diplopia or enophthalmos postoperatively. Using individually preformed titanium mesh implants, the accuracy of the 3D orbital reconstruction was within a range of 1mm. The reconstruction using preformed implants proved to be less time consuming, more precise and less invasive, compared to 'free hand' efforts, for the repair of orbital injuries using titanium mesh and calvarial grafts.


Subject(s)
Orbit/surgery , Orbital Fractures/surgery , Surgical Mesh , Biocompatible Materials/therapeutic use , Humans , Image Processing, Computer-Assisted/methods , Orbit/diagnostic imaging , Orbital Fractures/diagnostic imaging , Surgery, Computer-Assisted/methods , Titanium/therapeutic use , Tomography, X-Ray Computed
7.
FEBS Lett ; 359(2-3): 107-9, 1995 Feb 13.
Article in English | MEDLINE | ID: mdl-7867778

ABSTRACT

Since 1985, several research groups have shown that a number of amino acids in the catalytic alpha-subunit of Na+/K(+)-ATPase more or less strongly modulate the affinity of a digitalis compound like ouabain to the enzyme. However, scrutiny of these findings by means of chimeric Na+/K(+)-ATPase constructs and monoclonal antibodies has recently revealed that the modulatory effect of most of these amino acids does not at all result from direct interaction with ouabain, but rather originates from long-range effects on the properties of the digitalis binding matrix. Starting from this knowledge, the present review brings together the various pieces of evidence pointing to the conclusion that the interface between two interacting alpha-subunits in the Na+/K(+)-ATPase protodimer (alpha beta)2 provides the cleft for inhibitory digitalis intercalation.


Subject(s)
Sodium-Potassium-Exchanging ATPase/metabolism
8.
Thromb Haemost ; 71(1): 68-72, 1994 Jan.
Article in English | MEDLINE | ID: mdl-8165648

ABSTRACT

Factor XII (FXII) deficiency has been reported to be a risk factor for the development of arterial and venous thromboembolism. However, no data are available on the prevalence of FXII deficiency within the normal population. Measuring APTT and FXII activity, seven FXII deficiencies could be detected among 300 healthy blood donors. This corresponds to an incidence of FXII deficiency of 2.3%. On the basis of these data the prevalence of severe and mild FXII deficiency in the normal population can be estimated to be 1.5-3.0%. Assessment of FXII antigen levels revealed, that all seven FXII deficient individuals had FXII antigen levels matching the activity. One presented a severe FXII deficiency (1/300, 0.3%) without detectable FXII activity and an APTT prolongation of more than 120 s. The remaining six FXII deficiencies (6/300, 2.0%) were moderate variations with FXII activities ranging from 20-45% and less prolonged APTTs. Among the 300 healthy donors 16 (5.3%) subjects with prolonged APTTs were identified. Causes for APTT-prolongation were FXII deficiency (7/16), lupus anticoagulant (6/16), mild FVIII deficiency (1/16) and hepatic disorder (1/16). In the remaining sample (1/16) the cause for the prolongation of the APTT remained unexplained. Although 8.7% (26/300) of the donors had a positive family-history of thromboembolism (TE-FHx), none of the FXII deficient subjects were among those with positive TE-FHx.


Subject(s)
Factor XII Deficiency/epidemiology , Adult , Austria/epidemiology , Blood Donors , Factor XII/analysis , Factor XII Deficiency/etiology , Female , Hemophilia A/complications , Humans , Incidence , Liver Diseases/complications , Lupus Coagulation Inhibitor/analysis , Male , Partial Thromboplastin Time , Prevalence
9.
Biomaterials ; 12(2): 125-9, 1991 Mar.
Article in English | MEDLINE | ID: mdl-1878447

ABSTRACT

PVD-TiN coating and N+ implantation of Ti-6Al-7Nb alloy resulted in surface hardening to a depth of less 3 microns. The new oxygen diffusion hardening (ODH) treatment increased the hardness gradually to 50 microns. PUD-TiN showed an improvement in the tribological properties, while N+ implantation increased the PE wear rate. The wear rate of the ultrahigh-molecular-weight as well as the friction coefficient were reduced to one-half of the values achieved with the combination of CoCrMo-alloy when paired against the ODH-treated surface. In pairing with ZrO2-containing bone cement the ODH-treated surface showed only a minimal reaction.


Subject(s)
Materials Testing , Titanium , Corrosion , Molecular Weight , Surface Properties
10.
Biomaterials ; 13(11): 781-8, 1992.
Article in English | MEDLINE | ID: mdl-1391401

ABSTRACT

We have developed a titanium-aluminium alloy with the inert alloying element niobium. The optimal composition was found to be Ti-6Al-7Nb (Protasul-100). This custom-made alloy designed for implants shows the same alpha/beta structure as Ti-6Al-4V and exhibits equally good mechanical properties. The corrosion resistance of Ti-6Al-7Nb in sodium chloride solution is equivalent to that of pure titanium and Ti-6Al-4V. This is due to a very dense and stable passive layer. Highly stressed anchorage stems of different hip prosthesis designs have been made from hot-forged Ti-6Al-7Nb. The polished surfaces of hip, knee and wrist joints made of Ti-6Al-7Nb and articulating against polyethylene are surface-treated by means of a very hard and 3-5 microns thick titanium nitride coating (Tribosul-TiN) or by oxygen diffusion hardening (Tribosul-ODH) to a depth of 30 microns.


Subject(s)
Joint Prosthesis , Titanium/chemistry , Humans
11.
Naunyn Schmiedebergs Arch Pharmacol ; 351(3): 282-92, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7609782

ABSTRACT

The aims of the study included: to explore the protein structure basis for the differences in digitalis sensitivity between isoforms of Na/K-ATPase from human and guinea-pig cardiac muscle; to determine the relative significance of the constituents of tripartite digitalis compounds in their inhibitory action on these Na/K-ATPase isoforms; to evaluate the potential significance of the receptor kinetics for pharmacological characteristics. The analytical method has been the recording of the inhibitory interaction of various digitalis derivatives with the Na/K-ATPase isoforms. The protein structure basis for the isoform differences in digitalis susceptibility has been explored by analysing in free-energy plots the kinetics of their inhibitory interaction with 53 digitalis derivatives of grossly different structure. The slope of the regression line and the parameters of the regression equation proved to be similar for the two isoforms in spite of the great difference in their digitalis susceptibilities. This surprising uniformity indicates that a uniform "macroscopic" mechanism underlies the inhibitory effect of the various derivatives on the two isoforms. On the other hand, the differences in the positions of delta G*on and delta G*off values for particular inhibitors relative to the regression line reveal differences in the "microscopic" interaction energy surfaces of the two isoforms. In conclusion, the origin of the isoform distinctions in their susceptibility towards inhibition by various digitalis derivatives is essentially confined to differences in the chemotopology of the digitalis recognition matrix and binding cleft. Specific observations allowed to disentangle the impact of various steroid derivatizations at carbon atoms 3, 17, and diverse other positions on the kinetics of their interaction with the enzyme isoforms. The steroid nucleus of the cardiac glycosides, 5 beta, 14 beta-androstane, proves to be the basal structural element for discrimination of Na/K-ATPase isoforms. This discrimination becomes much enlarged by steroid glycosidation at C3 beta-OH and/or by steroid substitution of C17 beta-H by a lactone ring. The higher inhibitory sensitivity of the human isoform is based either on an increased association rate or a decreased dissociation rate, depending on the nature of derivatization.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Digitalis Glycosides/pharmacology , Isoenzymes/antagonists & inhibitors , Myocardium/enzymology , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Animals , Guinea Pigs , Humans , Isoenzymes/analysis , Isoenzymes/chemistry , Kinetics , Protein Conformation , Sodium-Potassium-Exchanging ATPase/analysis , Sodium-Potassium-Exchanging ATPase/chemistry , Species Specificity , Thermodynamics
12.
Neurosurgery ; 31(5): 969-70; discussion 970-1, 1992 Nov.
Article in English | MEDLINE | ID: mdl-1436428

ABSTRACT

A patient had a 10-year history of pain and swelling in the right wrist and palm. Carpal tunnel exploration showed anomalous muscle bellies of flexor digitorum superficialis II and III. The muscle bellies were excised. Postoperatively, the symptoms disappeared. Our case is compared with others in the literature.


Subject(s)
Carpal Tunnel Syndrome/surgery , Muscles/abnormalities , Adult , Carpal Tunnel Syndrome/congenital , Diagnosis, Differential , Humans , Male , Muscles/surgery , Neurologic Examination
13.
Steroids ; 36(2): 131-47, 1980 Aug.
Article in English | MEDLINE | ID: mdl-7444986

ABSTRACT

Following oral administration of 9,11-3H-17 alpha-cyanomethylestra-1,3,5(10)-triene-3,17-diol 3-methyl ether, urinary metabolites were studied in man, baboon, beagle dog, minipig and rat. The metabolite pattern revealed remarkable species differences, especially in quantitative respects. 17 alpha-Cyanomethylestra-1,3,5(10)triene-3,17-diol, 17 alpha-cyanomethylestra-1,3,5(10)-triene-2,3,17-triol 2-methyl ether, 17 alpha-hydroxymethylestra-1,3,5(10)-triene-3,17-diol and 17 alpha-cyanomethylestra-1,3,5(10)-triene-3,16 xi, 17-triol were isolated as principal metabolites. In rat bile, a metabolite was tentatively identified as a gamma-lactone of a 17 alpha-carboxymethyl-16 alpha-hydroxy compound.


Subject(s)
Estradiol/analogs & derivatives , Animals , Bile/metabolism , Biotransformation , Dogs , Estradiol/metabolism , Estradiol/urine , Female , Humans , Male , Papio , Rats , Species Specificity , Swine
14.
Steroids ; 62(12): 762-6, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9434341

ABSTRACT

3-Oxo-17 alpha-pregna-4,6-diene-21,17-carbolactone (canrenone, II) is produced from the potassium salt of 17-hydroxy-3-oxo-17 alpha-pregna-4,6-diene-21-carboxylic acid (I) by acid catalyzed lactonization. II reacts with acetic anhydride/nitric acid to give one main product (III) and some minor products. The structure of III was determined by chemical and spectral analysis to the 4-nitro derivative of canrenone. This result is in contrast to the known reactions of II with most other reagents that were found to add at delta(6), and also in contrast to the reactions of acetic anhydride/nitric acid with alkenes. Electrophilic substitution at the ambident C4 is discussed as the reaction path. The 4-nitro group enhances the inhibitory activity of II against Na+/K(+)-ATPase, the target enzyme of the cardioactive digitalis glycosides, which appears to indicate increased cardioactivity.


Subject(s)
Acetic Acid/chemistry , Canrenone/analogs & derivatives , Canrenone/chemistry , Nitrates/chemistry , Nitric Acid/chemistry , Canrenone/chemical synthesis , Canrenone/pharmacology , Magnetic Resonance Spectroscopy , Mass Spectrometry , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Ultraviolet Rays
15.
Steroids ; 63(7-8): 393-400, 1998.
Article in English | MEDLINE | ID: mdl-9654645

ABSTRACT

The biotransformation of the progestagen dienogest (17 alpha-cyanomethyl-17 beta-hydroxy-4,9-estradien-3-one) was studied in vivo in female rabbits and in vitro by liver homogenates from female rabbits and rats. In vivo, in the female rabbit, 3H-dienogest was the subject of an extensive biotransformation. A significant difference between the composition of the urinary and biliary metabolite patterns of dienogest was found. While in the urinary metabolite pattern more polar metabolites dominated, in bile of animals with a bile fistula, a dienogest metabolite of medium polarity was prevalent. This main metabolite of dienogest was identified by MS, 1H- and 13C-NMR spectroscopy and CD measurement of an enzymatic dehydrogenation product as the tetrahydro metabolite 17 alpha-cyanomethyl-5 alpha-estr-9-en-3 beta,17 beta-diol. Thus, in vivo, the 4,9-dien-3-oxo-19-norsteroid dienogest is hydrogenated to a 5 alpha H-9-en metabolite. In vitro, however, 3H-dienogest was only poorly transformed by liver homogenates from both species, whereas 3H-levonorgestrel and 3H-3-keto-desogestrel were converted partially by liver homogenates from female rabbits and completely by liver homogenates from female rats. The principal biotransformation reactions of levonorgestrel and 3-ketodesogestrel were the reduction of the 3-oxo group to 3-OH and the 5 beta- and 5 alpha-hydrogenation of the 4-double bond by homogenates of female rabbit liver and female rat liver, respectively. A dihydro metabolite of dienogest, in which the 3-oxo group had been reduced to 3-OH, was isolated in small amounts from the incubation with rabbit liver homogenate. The data indicate that the enzymatic hydrogenation of the 4-double bond of the 4,9-dien-3-oxo steroid dienogest is inhibited in vitro. The hindered hydrogenation reaction in vitro has to be seen in association with the 9-double bond in the steroid molecule.


Subject(s)
Nandrolone/analogs & derivatives , Animals , Bile/metabolism , Biotransformation , Contraceptives, Oral/metabolism , Desogestrel/metabolism , Female , Hydrogenation , Levonorgestrel/metabolism , Liver/enzymology , Liver/metabolism , Magnetic Resonance Spectroscopy , Male , Nandrolone/metabolism , Nandrolone/urine , Rabbits , Rats , Rats, Wistar
16.
Steroids ; 41(1): 23-33, 1983 Jan.
Article in English | MEDLINE | ID: mdl-6658863

ABSTRACT

Urinary metabolites of the new progestagen STS 557 (17 alpha-cyanomethyl-17-hydroxy-4,9-estradien-3-one) were isolated and characterized following oral administration of the 14 alpha, 15 alpha-tritium labelled compound to dogs and rats. 17 alpha-Cyanomethyl-11 beta, 17-dihydroxy-4,9-estradien-3-one (11 beta-OH-STS 557) and 17 alpha-cyanomethyl-1,3,5(10),9(11)-estratetraene-3,17-diol were identified by comparison with synthesized reference compounds. Mass spectra data indicate the following other pathways of STS 557 biotransformation: Hydroxylation in other positions than 11; hydrogenation; hydroxylation + hydrogenation; alteration of the 17 alpha-side chain.


Subject(s)
Nandrolone/analogs & derivatives , Progesterone Congeners/urine , Administration, Oral , Animals , Chromatography, Thin Layer , Dogs , Female , Kinetics , Male , Mass Spectrometry , Nandrolone/administration & dosage , Nandrolone/urine , Rats , Rats, Inbred Strains , Species Specificity , Spectrophotometry, Ultraviolet
17.
Steroids ; 39(4): 399-409, 1982 Apr.
Article in English | MEDLINE | ID: mdl-7179349

ABSTRACT

Microbial transformation of the new progestagen STS 557 (17 alpha-cyanomethyl-17-hydroxy-4,9-estradien-3-one) by Mycobacterium smegmatis yielded predominantly ring A-aromatized compounds: 17 alpha-cyanomethyl-1,3,5(10),9(11)-estratetraene-3, 17-diol, 17 alpha-cyanomethyl-1,3,5(10)-estratriene-3,17-diol and the corresponding 3-methyl ethers. The analogous compound without the 9(10) double bond, 17 alpha-cyanomethyl-19-nortestosterone, was transformed mainly to 5 alpha-hydrogenated metabolites: 17 alpha-cyanomethyl-17-hydroxy-5 alpha-estran-3-one, 17 alpha-cyanomethyl-17-hydroxy-5 alpha-1-estren-3-one, 17 alpha-cyanomethyl-5 alpha-estrane-3 alpha, 17-diol, and 17 alpha-cyanomethyl-5 alpha-estrane-3 beta, 17-diol. From these results, it is concluded that 4,9-dien-3-oxo compounds are not substrates for enzymatic 5 alpha-hydrogenation.


Subject(s)
Mycobacterium/metabolism , Nandrolone/analogs & derivatives , Biotransformation , Chemical Phenomena , Chemistry , Hydrogenation , Nandrolone/metabolism
18.
Steroids ; 62(5): 437-43, 1997 May.
Article in English | MEDLINE | ID: mdl-9178431

ABSTRACT

Specific microbial reactions were used for the preparation of metabolites of 3-ketodesogestrel (13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one, the active from of the progestagen desogestrel. Clostridium paraputrificum transformed 3-ketodesogestrel (KDG) to the 5 beta-dihydro and tetrahydro metabolites 13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yn-3-one and 13-ethyl-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yne-3 alpha, 17 beta-diol, respectively. The epimeric compound 13-ethyl-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yne-3 beta, 17 beta-diol was obtained by chemical reduction of the 3-oxo compound. Mycobacterium smegmatis converted KDG to metabolites of the 5 alpha H-series: 13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yn-3-one, 13-ethyl-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yne-3 alpha, 17 beta-diol and 13-ethyl-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yne-3 beta, 17 beta-diol. The ring A-aromatized analog of KDG 13-ethyl-11-methylene-18,19-dinor-17 alpha-pregna-1,3,5(10)-trien-20-yne-3,17 beta-diol was obtained by microbial 1-dehydrogenation with Rhodococcus rhodochrous. Additionally, chemical syntheses of the microbially obtained KDG metabolites listed above were carried out. These included Birch reduction, reduction of KDG with sodium borohydride in aqueous pyridine and in methanol, reduction of KDG with potassium selectride in tetrahydrofuran, and dehydrogenation of KDG with cupric-II bromide in acetonitrile. The problems encountered in chemical syntheses favor the microbial procedures. The compounds were characterized by mass spectra (MS), IR, and circular dichroism (CD). Complete assignments of 1H and 13C chemical shifts were made using homo- and heteronuclear 2-DN-NMR spectroscopy. Chromatographic [gas-liquid chromatography (GLC), high-performance liquid chromatography (HPLC), thin-layer chromatography (TLC)] data of all the prepared KDG metabolites are presented.


Subject(s)
Desogestrel/metabolism , Progesterone Congeners/metabolism , Clostridium/metabolism , Mycobacterium/metabolism , Rhodococcus/metabolism
19.
Steroids ; 63(9): 464-9, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9727093

ABSTRACT

To improve the weak inhibitory effect of 3-oxo-17 alpha-pregna-4,6-diene-21,17-carbolactone (canrenone, II) on Na+/K(+)-ATPase activity in human heart muscle, we have investigated the impact of hydrogenation, reduction, glycosidation, and the introduction of a 3-sulfonamido residue on the inhibitory potency of canrenone. The greatest increase in potency (> 20 times) was found for 3 beta-(alpha-L-rhamnopyranosyloxy)-5 beta, 17 alpha-pregnane-21, 17-carbolactone (IX). The 3-O-glycosides IX-XI are the first representatives of C/D-trans steroids with effector-receptor complex decay half-times longer than those of therapeutically used cardenolides.


Subject(s)
Canrenone/pharmacology , Myocardium/enzymology , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Canrenone/chemistry , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Glycosides/chemistry , Humans , Hydrogenation , Magnetic Resonance Spectroscopy , Mass Spectrometry , Sulfonamides/chemistry
20.
Coron Artery Dis ; 6(5): 397-402, 1995 May.
Article in English | MEDLINE | ID: mdl-7655727

ABSTRACT

BACKGROUND: An increase in mean platelet volume has been reported to be associated with arterial thrombosis and myocardial infarction. A larger mean platelet volume has been regarded as an independent risk factor for recurrent myocardial infarction. We therefore investigated whether it is also increased in patients with coronary heart disease examined a few days before cardiac surgery. METHODS: Four hundred and twenty-six patients with coronary heart disease who were waiting for cardiac surgery and 125 healthy individuals were included in the study. Mean platelet volume and other platelet parameters were obtained from a routine blood count procedure using a flow cytometric haematology analyser. RESULTS: Mean platelet volume did not differ significantly between patients and controls; however, as expected from the literature, patients had significantly elevated levels of fibrinogen, cholesterol, triglyceride, apolipoprotein B and apolipoprotein(a). Furthermore, we observed no significant difference in mean platelet volume between patients without myocardial infarction and those who had survived at least one myocardial infarction. CONCLUSION: Our findings suggest that, using a routine laboratory procedure, mean platelet volume cannot be used as a predictive marker for coronary heart disease or myocardial infarction.


Subject(s)
Blood Platelets/pathology , Coronary Disease/blood , Fibrinogen/analysis , Lipoprotein(a)/blood , Adult , Case-Control Studies , Cell Separation , Female , Flow Cytometry , Humans , Male , Middle Aged , Myocardial Infarction/blood , Platelet Function Tests , Risk Factors
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