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Biomedical subjects

D H Nguyen

Publications and source records attributed to D H Nguyen.

At least 37 records · Page 2Linked to original sources
PubMed1999

The very low density lipoprotein receptor regulates urokinase receptor catabolism and breast cancer cell motility in vitro.

The very low density lipoprotein receptor (VLDLr) binds diverse ligands, including urokinase-type plasminogen activator (uPA) and uPA-plasminogen activator inhibitor-1 (PAI-1) complex. In this study, we characterized the effects of the VLDLr on the internalization, catabolism, and function of the uPA receptor (uPAR) in MCF-7 and MDA-MB-435 breast cancer cells. When challenged with uPA.PAI-1 complex, MDA-MB-435 cells internalized uPAR; this process was inhibited by 80% when the activity of the VLDLr was neutralized with receptor-associated protein (RAP). To determine whether internalized uPAR is degraded, we studied the catabolism of [35S]methionine-labeled uPAR. In the absence of exogenous agents, the uPAR catabolism t(1)/(2) was 8.2 h. uPA.PAI-1 complex accelerated uPAR catabolism (t(1)/(2) to 1.8 h), while RAP inhibited uPAR catabolism in the presence (t(1)/(2) of 7.8 h) and absence (t(1)/(2) of 16.9 h) of uPA.PAI-1 complex, demonstrating a critical role for the VLDLr. When MCF-7 cells were cultured in RAP, cell surface uPAR levels increased gradually, reaching a new steady-state in 3 days. The amount of uPA which accumulated in the medium also increased. Culturing in RAP for 3 days increased MCF-7 cell motility by 2.2 +/- 0.1-fold and by 4.4 +/- 0.3-fold when 1.0 nM uPA was added. The effects of RAP on MCF-7 cell motility were entirely abrogated by an antibody which binds uPA and prevents uPA binding to uPAR. MCF-7 cells that were cultured in RAP demonstrated increased levels of activated mitogen-activated protein kinases. Furthermore, the MEK inhibitor, PD098059, decreased the motility of RAP-treated cells without affecting control cultures. These studies suggest a model in which the VLDLr regulates autocrine uPAR-initiated signaling and thereby regulates cellular motility.

Breast Neoplasms↗
PubMed1999

Characterization of immortalized rabbit lacrimal gland epithelial cells.

To establish an immortalized lacrimal gland epithelial cell line, the orbital lacrimal glands of normal New Zealand White rabbits were multiply injected with an immortalizing amphotropic retroviral vector (LXSN16E6E7) containing the E6 and E7 genes of human papillomavirus type 16. Lacrimal glands were removed after 2 d and acinar epithelial cells were isolated and cultured on Matrigel-coated 60 mm2 plates containing DMEM-F12 supplemented with 5% Nu-serum V. Transformed cells were selected in G418 sulfate for 7 d and passaged. Morphology of the immortalized cells was similar to that described for normal acinar cells both in vivo and in vitro, with rough endoplasmic reticulum and secretory granules. These characteristics remained unchanged and the cells continued to exhibit typical polygonal epithelioid structure. The cells have been maintained in culture for 14 mo. and have gone through 58 passages without loss of proliferation or epithelial cell characteristics. Immunohistochemistry and Western blots showed positive reactivity to secretory component, transferrin, and transferrin receptor, which are typical proteins found in the lacrimal gland. Functional analysis by stimulation with a cholinergic agonist, carbachol (100 microM), resulted in a significant release of protein. This is the first report of an immortalized rabbit lacrimal epithelial cell. These cells will provide a valuable tool for the molecular analysis of lacrimal gland epithelial cell functions.

Animals↗
PubMed1999

The channel-forming toxin aerolysin neutralizes human immunodeficiency virus type 1.

Aerolysin is a channel-forming toxin secreted by Aeromonas spp. that binds to glycosyl phosphatidylinositol (GPI)-anchored proteins, such as Thy-1, on sensitive target cells. Receptor binding is followed first by oligomerization of the toxin and then by insertion of the oligomers into the membrane to form stable channels that disrupt the permeability barrier. Human immunodeficiency virus type 1 (HIV-1) produced from T cells is known to incorporate Thy-1 and other GPI-anchored proteins into its membrane. Here, we show that aerolysin is capable of neutralizing HIV-1 in a dose-dependent manner and that neutralization depends upon the presence of these proteins in the viral envelope. Pretreatment with phosphatidylinositol-specific phospholipase C to remove GPI-anchored proteins greatly reduced HIV-1 sensitivity to the toxin, and virus originating from a mutant cell line that lacks GPI-anchored proteins was not neutralized. Aerolysin variants with single amino acid changes that prevent oligomerization or insertion of the toxin were unable to inactivate the virus, implying that channel formation is necessary for neutralization to occur. These findings represent the first evidence that a pathogenic human virus can be neutralized by a bacterial toxin.

Anti-HIV Agents↗
PubMed1999

Macro- and trace element concentrations in blood plasma and cerebrospinal fluid of dairy cows exposed to electric and magnetic fields.

Eight multiparous, nonlactating pregnant Holstein cows (at 198 +/- 35 days of gestation and weighing 608 + 24 kg) and seven nonlactating nonpregnant ovariectomized heifers (weighing 370 + 29 kg) were confined to wooden metabolism crates in an electric and magnetic field chamber. Subarachnoidal catheters were inserted before the activation of the electric and magnetic fields. For 30 days, cows and heifers were continuously exposed in separate trials to electric and magnetic fields (60 Hz, 10 kV/m, and 30 microT). Blood plasma and cerebrospinal fluid samples were collected for 3 consecutive days before the exposure period, the last 3 days of the exposure period, and for 3 days starting 5 days after the exposure period. Concentrations of Ca, Mg, Cu, Zn, Fe, Mn, Na, P, and K in blood plasma and cerebrospinal fluid were determined. Exposure to electric and magnetic fields resulted in decreased concentrations of Mg in blood plasma and in increased concentrations of Ca and P and decreased concentrations of Fe and Mn in cerebrospinal fluid.

Animals↗
PubMed1998

Binding of urokinase-type plasminogen activator to its receptor in MCF-7 cells activates extracellular signal-regulated kinase 1 and 2 which is required for increased cellular motility.

Binding of urokinase-type plasminogen activator (uPA) to its receptor, uPAR, regulates cellular adhesion, migration, and tumor cell invasion. Some of these activities may reflect the ability of uPAR to initiate signal transduction even though this receptor is linked to the plasma membrane only by a glycosylphosphatidylinositol anchor. In this study, we demonstrated that single-chain uPA activates extracellular signal-regulated kinase 1 (ERK1) and ERK2 in MCF-7 breast cancer cells. Phosphorylation of ERK1 and ERK2 was increased 1 min after adding uPA and returned to baseline levels by 5 min. The amino-terminal fragment (ATF) of uPA, which binds to uPAR but lacks proteinase activity, also activated ERK1 and ERK2. Responses to uPA and ATF were eliminated when the cells were pretreated with PD098059, an inhibitor of mitogen-activated protein kinase kinase. uPA and ATF promoted the migration of MCF-7 cells across serum-coated Transwell membranes in vitro. Migration was increased 2.1 +/- 0.4-fold when uPA was added to the top chamber, 4. 8 +/- 0.8-fold when uPA was added to the bottom chamber, and 7.7 +/- 1.0-fold when uPA was added to both chambers. MCF-7 cells that were pulse-exposed to uPA for 30 min, and then washed to remove unbound ligand, demonstrated increased motility even though migration was allowed to occur for 24 h. PD098059 completely neutralized the effects of uPA on MCF-7 cellular motility, irrespective of whether the uPA was present for the entire motility assay or administered by pulse-exposure. These results demonstrate a novel, receptor-dependent signaling activity which is required for uPA-stimulated breast cancer cell migration.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Effects of electromagnetic fields on the levels of biogenic amine metabolites, quinolinic acid, and beta-endorphin in the cerebrospinal fluid of dairy cows.

Eight multiparous non-lactating pregnant Holstein cows at 198 +/- 35 d of gestation, weighing 608 +/- 24 kg, were confined to wooden metabolic cages in an electric and magnetic field chamber with a 12:12 h light:dark cycle. Subarachnoidal catheters were installed 5 d before the activation of the electric and magnetic fields. The cows were exposed to electric and magnetic fields (60 Hz, 10 kV/m and 30 microT) continuously except for the feeding and cleaning time for an average of 21.44 +/- 1.4 h per day for a period of 30 d. Cerebrospinal fluid samples were collected on three consecutive days before an exposure period of 30 d, on the last 3 d of the exposure period, and for 3 d starting 5 d after the exposure period. The concentrations of beta-endorphin, tryptophan, 5-hydroxyindoleacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylethyleneglycol and quinolinic acid in cerebrospinal fluid were determined. There was a significant increase in quinolinic acid, and a trend towards an increase in tryptophan, findings consistent with a weakening of the blood-brain barrier due to exposure to the electric and magnetic fields.

Animals↗
PubMed1998

Effect of sensory denervation on the structure and physiologic responsiveness of rabbit lacrimal gland.

PURPOSE: This work was conducted to determine the effects of unilateral trigeminal ganglion ablation on lacrimal gland structure and secretory activity. METHODS: Adult male New Zealand rabbits underwent unilateral thermocoagulation of the ophthalmic division of the trigeminal ganglion. Sensory denervation was affirmed by anatomic inspection of the lesion and transmission electron microscopy (TEM) of the lacrimal gland innervation. Eight to 10 days after the procedure, the intraorbital lacrimal glands were removed from both sides. To compare the physiologic competence of the intact and denervated glands, freshly isolated gland fragments from the paired intact and denervated glands were stimulated with carbachol (100 microM), isoproterenol (10 microM), phorbol-12,13-dibutyrate (PDBu, 10 microM), forskolin (40 microM), or vehicle. Total secreted protein was measured at 30 or 60 min after the establishment of baseline values. Intact and denervated glands also were examined by light and TEM, and the morphologic appearance of the acinar structures as well as the appearance of nerves innervating the gland after denervation were assessed. Similar experiments were conducted with animals that underwent unilateral superior cervical ganglionectomy. RESULTS: Tissues from sensory denervated glands released significantly more protein than did tissues from innervated glands in response to in vitro stimulation by carbachol or isoproterenol but not in response to PDBu or forskolin. Microscopy showed that the acinar cells that had undergone sensory denervation showed a massive accumulation of secretory granules. The secretory granules filled the entire cytoplasmic space and displaced the ellipsoidal nuclei to the extreme periphery. Examination of segments of nerves revealed numerous unmyelinated axons, a few small-diameter myelinated axons, and a large amount of nerve degeneration after sensory denervation. In contrast to the effects of sensory denervation, sympathetic denervation did not alter either the acinar appearance or secretory responsiveness of the gland. CONCLUSION: Loss of the considerable sensory innervation from the trigeminal ganglion has pronounced effects on the pharmacologic responsiveness and the structure of the lacrimal gland. The effects of sensory innervation on the gland may be mediated through two possible pathways: direct input to the gland or control of the preganglionic parasympathetic pathway.

Animals↗
PubMed1998

Effects of electric and magnetic fields on nocturnal melatonin concentrations in dairy cows.

Sixteen multiparous, pregnant, lactating Holstein cows (weighing 600 +/- 50 kg, at 184.8 +/- 52 d of lactation, and at 101.9 +/- 43 d of gestation) were confined to wooden metabolism cages and exposed to a vertical electric field of 10 kV/m and a uniform horizontal magnetic field of 30 microT. The trial was conducted using a switchback statistical design. Cows were divided into two sequence groups of 8 cows each. One sequence group was exposed for three periods of 28 d each. The electric and magnetic fields were off during the first period, on during the second period, and off during the final period. The second sequence group was exposed for three periods also, but the activity of the fields was reversed (on during the first period, off during the second period, and on during the third period). On d 25 of each exposure period, blood samples were obtained every 0.5 h for 14 h starting at 1700 h to determine melatonin concentration. Nocturnal melatonin concentrations did not show any variation that could be attributed to exposure to electric and magnetic fields.

Animals↗
PubMed1998

Progesterone concentrations during estrous cycle of dairy cows exposed to electric and magnetic fields.

Sixteen multiparous nonpregnant lactating Holstein cows (each weighing 662 +/- 65 kg in 150.4 +/- 40 day of lactation) were confined to wooden metabolic cages with 12:12 h light:dark cycle during the experiment. The cows were divided into two sequences of eight cows each and exposed to electric and magnetic fields (EMF) in an exposure chamber. This chamber produced a vertical electric field of 10 kV/m and a uniform horizontal magnetic field of 30 microT at 60 Hz. One sequence was exposed for three estrous cycles of 24 to 27 days. During the first estrous cycle, the electric and magnetic fields were off; during the second estrous cycle, they were on; and during the third estrous cycle, they were off. The second sequence was also exposed for three 24 to 26 days estrous cycles, but the exposure to the fields was reversed (first estrous cycle, on; second estrous cycle, off; third estrous cycle, on). The length of each exposure period (21 to 27 days) varied according to the estrous cycle length. No differences were detected in plasma progesterone concentrations and area under the progesterone curve during estrous cycles between EMF nonexposed and exposed periods (2.28 +/- 0.17 and 2.25 +/- 0.17; and 24.5 +/- 1.9 vs. 26.4 +/- 1.9 ng/ml, respectively). However, estrous cycle length, determined by the presence of a functional corpus luteum detected by concentrations of progesterone equal to or more than 1 ng/ml plasma, was shorter in nonexposed cows than when they were exposed to EMF (22.0 +/- 0.9 vs. 25.3 +/- 1.4 days).

Animals↗
PubMed1997

Fibrin sealant reduces serous drainage and allows for earlier drain removal after axillary dissection: a randomized prospective trial.

Fibrin sealant (FS) has been used successfully as an effective adhesive and hemostatic agent in a variety of surgical procedures. At the University of Virginia, autologous fibrin sealant is used to reduce the potential accumulation of serous fluid after axillary dissection in patients undergoing modified radical mastectomy (MRM) for carcinoma of the breast. Unilateral MRM, including level I and II axillary lymph node dissection, was performed upon 21 patients prospectively randomized into treatment and control groups. Surgical procedures between both groups differed only by the application of autologous FS prior to axilla closure in the treatment group. Drainage was collected and measured at 24-hour intervals following the operation. Drains were removed following the measurement of 40 ml or less during a 24-hour interval. Cumulative drainage for the first 3 postoperative days in the treatment group averaged 198 +/- 83 ml compared to 467 +/- 138 ml in the control group (P < 0.0003). Day of drain removal averaged 3.9 +/- 1.7 for the treatment group and 6.9 +/- 1.2 for the control group (P < 0.0001). In the treatment group, there was a reduction in cumulative drainage over the first 3 days of 268 ml or 57 per cent, and there was a reduction in the number of days before drains can be removed of 3.0 days, or 43 per cent. We conclude that local application of FS significantly reduced the total drainage measured in patients undergoing MRM and enabled earlier drain removal.

Aged↗
PubMed1997

Growth factor and neurotrophic factor mRNA in human lacrimal gland.

PURPOSE: This study examined the expression of important growth factor and receptor messenger RNA (mRNA) in human lacrimal gland. METHOD: Lacrimal gland tissue was obtained from six women, aged 31-85 years, who were undergoing surgery. The specimens were frozen immediately in liquid nitrogen. Total cellular RNA was collected by cesium chloride centrifugation, and the integrity of the RNA was analyzed by gel electrophoresis and spectrophotometry. For the reverse-transcription polymerase chain reaction (RT-PCR) procedure, 1 microgram of total cellular RNA was used for the first strand synthesis and amplified in separate reactions for 34 cycles by using primers specific for transforming growth factor-beta 1, -beta 2, and -beta 3 (TGF beta 1, TGF beta 2, TGF beta 3), TGF beta 3 receptor (TGF beta 3R), basic fibroblast growth factor (bFGF), fibroblast growth factor receptor-1 (FGF-R1), nerve growth factor (beta-NGF), low-affinity NGF receptor (p75NGF-R), and platelet-derived growth factor-AA (PDGF-AA; two of the six cases) and -BB (PDGF-BB; three of the six cases). Product identity was confirmed by restriction endonuclease digestion, by the "hot blot" technique, by DNA sequencing, or by a combination of these. RESULTS: All the lacrimal gland specimens were positive for all growth factors, neurotrophic factors, and receptors except for two specimens that were negative for bFGF. The patients from whom the bFGF-negative specimens were obtained were 68 and 74 years old, and both were identified as having dry eyes-one severe and the other moderate, respectively. These specimens were also analyzed for PDGF-AA and PDGF-BB mRNA, and both were positive. CONCLUSIONS: This study demonstrates that RT-PCR is a rapid and sensitive method for analyzing rare mRNA transcripts in small amounts of tissue. The results suggest that these growth and neurotrophic factors may have autocrine and paracrine roles in modulating the lacrimal gland, and their absence may play a role in pathologic states such as fibrosis and dry eyes.

Adult↗
PubMed1997

Role of adenosine-triphosphate-sensitive potassium channels in the mechanical responses of agonist-stimulated isolated porcine coronary arteries.

The aim of this study was to provide evidence supporting the hypothesis that the reactivity of the vascular smooth muscle (VSM) cell is controlled at the cell membrane level by adenosine triphosphate (ATP)-sensitive (KATP) K channels, acting as signal amplifying modulators of the function of L-type voltage operated Ca channels. KATP channels, detected in numerous parts of the vascular tree, are targets for extracellular ATP or adenosine, which stimulate A2 receptors mediating relaxation. To test the hypothesis of a putative role for KATP channels switching between vasoconstricting and vasodilating mechanisms, changes in contractile reactivity were measured in helical strips of epicardial porcine coronary artery preparations in response to various vasoconstrictor and vasodilator substances or combination of these. The data show that the tonic component of the biphasic contractions induced by several agonists (acetylcholine, histamine, serotonin), as well as the contractions induced by F- ions (2 mmol/l), which activate G proteins downstream of the receptors could be inhibited by both adenine nucleotides and by cromakalim, known as openers of KATP channels. The EC50 values for the dose-response curves established for the inhibition of histamine-induced contractions by adenosine were nearly identical to those obtained for the relaxations of fluoride-induced contractions by cromakalim: resp. 0.556 +/- 0.081 and 0.590 +/- 0.052 mumol/l (n = 6). Contractions induced by BAY k 8644 (20 nmol/l), by tetraethylammonium (5 mmol/l) or by beta-methyldigoxin (1 mumol/l) were also strongly inhibited by 1 mumol/l cromakalim. From the results obtained in this study, it may be concluded that KATP channels could possibly play an integrative role in the signal transduction mechanism in VSM in that they act as common effectors for both vasoconstrictor and vasodilator agonists.

Adenosine↗
PubMed1996

Human perception of electric fields and ion currents associated with high-voltage DC transmission lines.

The objective of this study was to assess the ability of humans to detect the presence of DC electric field and ion currents. An exposure chamber simulating conditions present in the vicinity of high-voltage DC (HVDC) lines was designed and built for this purpose. In these experiments, the facility was used to expose observers to DC electric fields up to 50 kV/m and ion current densities up to 120 nA/m2. Forty-eight volunteers (25 women and 23 men) between the ages of 18 and 57 years served as observers. Perception of DC fields was examined by using two psychophysical methods: an adaptive staircase procedure and a rating method derived from signal-detection theory. Subjects completed three different series of observations by using each of these methods; one was conducted without ion currents, and the other two involved various combinations of electric fields and ion currents. Overall, subjects were significantly more likely to detect DC fields as the intensity increased. Observers were able to detect the presence of DC fields alone, but only at high intensities; the average threshold was 45 kV/m. Except in the most sensitive individuals, ion current densities up to 60 nA/m2 did not significantly facilitate the detection of DC fields. However, higher ion current densities were associated with a substantial lowering of sensory thresholds in a large majority of observers. Data analysis also revealed large variations in perceptual thresholds among observers. Normative data indicating DC field and ion current intensities that can be detected by 50% of all observers are provided. In addition, for the most sensitive observers, several other detection proportions were derived from the distribution of individual detection capabilities. These data can form the basis for environmental guidelines relating to the design of HVDC lines.

Adolescent↗
PubMed1996

Seroma prevention in a rat mastectomy model: use of a light-activated fibrin sealant.

Seroma formation following mastectomy and axillary dissection remains a common and significant problem contributing to patient morbidity and health-care costs. Previous data have suggested that fibrin sealant (FS), a biological adhesive, is capable of controlling lymphatic leakage and assisting with skin graft adhesion. In this study, the use of an experimental, light-activated FS under development by CryoLife (CFS) was evaluated in a rat mastectomy model in order to reduce seroma formation. CFS is a premixed form of FS, containing an inactivator that is reversed in the presence of light, causing sealant to form. In this model, rats underwent mastectomy and extensive dissection of the axillary lymphovasculature. Next, 1 ml of saline or FS was applied to the operative site and the wound was closed. Three groups of animals were evaluated 5 days postoperatively by measuring the volume (in milliliters) of seroma able to be aspirated from the surgical site. The saline control group (N = 20) had a seroma volume (mean +/- standard deviation [SD]) of 4.2 +/- 2.9 ml, while a form of CFS containing human fibrinogen (80 to 100 mg per milliliter) and human thrombin (20 U per milliliter) (N = 20) had a significantly smaller seroma volume of 1.1 +/- 1.6 ml (p < 0.001 analysis of variance). University of Virginia (UVA) FS, containing human fibrinogen (20 mg per milliliter) and bovine thrombin (500 U per milliliter) (N = 20), had a seroma volume of 2.0 +/- 1.6 ml (p < 0.01, compared to control; p > 0.2, compared to CFS). Thus, this form of CFS significantly reduced seroma formation compared to saline control and also appeared to result in a smaller fluid accumulation than with UVA FS, although this trend was not statistically significant. These data suggest that the use of CFS may help to reduce seroma formation in humans.

Animals↗
PubMed1996

Biological effects of electric and magnetic fields on productivity of dairy cows.

Sixteen multiparous Holstein cows (weighing 600 +/- 50 kg, in 184.8 +/- 52 d of lactation, and at 101.9 +/- 43 d of gestation) were confined to wooden metabolic cages and exposed to a vertical electric field of 10 kV/ m and to a uniform horizontal magnetic field of 30 microT (microtesla). The trial was conducted as a switch-back statistical design. Cows were divided into two replicates of 8 cows each. One replicate was exposed for three periods of 28 d each. During the first period, the electric and magnetic fields were off; during the second period, they were on; and, during the final period, they were off. The second replicate was exposed for three periods also, but the activity of the fields was reversed (first period, on; second period, off; and third period, on). Blood samples were obtained twice weekly for the determination of cortisol and progesterone and once weekly for the determination of pH and blood gases. Milk samples were collected once weekly to determine milk components (fat, protein, SNF, and SCC). Milk yield and feed consumption were measured daily. Most of the variables studied (bicarbonate, pH, O2 and CO2 partial pressures, cortisol concentration in blood, uncorrected milk yield, and milk components other than milk fat) showed no variation that could be attributed to exposure to electric and magnetic fields. Associations were found between the electric and magnetic fields and increased DMI, 4% FCM yield, milk fat content, and plasma progesterone.

Animals↗
PubMed1996

Demucosalized augmentation gastrocystoplasty with bladder autoaugmentation in pediatric patients.

PURPOSE: Potential metabolic complications in urinary reconstruction with bowel or stomach are due to the presence of the gastrointestinal mucosal layer. The advantage or disadvantage of each tissue has been debated. We report a procedure in which the mucosa of a gastric pedicle flap is removed and the remaining muscularis flap is transferred to an autoaugmented bladder. MATERIALS AND METHODS: Seven female and 4 male patients underwent the procedure at our institutions from October 1992 to November 1994. A retrospective chart review was performed to compare preoperative to postoperative urodynamic findings, continence status and complications. RESULTS: Mean followup was 23 months (range 8 to 33). Preoperative urodynamics showed an average bladder capacity of 109 cc (range 45 to 200) and compliance of 3 ml./cm. water (range 1 to 6). Urinary continence was achieved in 10 patients on clean intermittent catherization every 3 to 4 hours and 1 was wet due to low urethral resistance. All patients underwent postoperative urodynamics. Bladder capacity increased to 236 cc (range 150 to 300) with an average compliance of 9 ml./cm. water (range 5 to 14). No metabolic complications were noted. CONCLUSIONS: The gastric muscularis appears to be preserved along with the native urothelium to provide a compliant tissue that can be an alternative to bowel and stomach for bladder augmentation. Because the procedure involves demucosalizing the gastric patch as well as performing bladder autoaugmentation, operative time is increased compared to normal gastrocystoplasty or enterocystoplasty. However, the lack of metabolic complications and mucus-free urine are important considerations and substantial advantages.

Adolescent↗
PubMed1995

Biotransformation of corticosteroids by Penicillium decumbens ATCC 10436.

The biotransformation of a series of corticosteroids by the fungus Penicillium decumbens ATCC 10436 has been investigated. Conversion to the corresponding 5 alpha-dihydrosteroid was observed for all the delta 4-3-ketosteroids studied with the exception of deoxycorticosterone, which was converted to a delta 1.4-diene. Deoxycorticosterone acetate was, however, converted to a 5 alpha-dihydro product concomitant with ester hydrolysis. Other substrates carrying a C-21 acetoxy group were also hydrolyzed to the alcohol. In two cases (resulting from deoxycorticosterone acetate and 11-deoxycortisone) the 5 alpha-3-keto product was further reduced to the 3 beta-alcohol. No reduction of delta 1.4-dienes was observed.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗