Search PubMed⌕ Search

Biomedical subjects

M A Costa

Publications and source records attributed to M A Costa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Management challenges on small-scale gold mining activities in Brazil.

This article presents a focused study of environmental management in small-scale gold mining, called garimpo, at the Tapajós River in the Amazon basin (Brazil). Environmental management is necessary in this very important area not only for Brazil but for the general world welfare. The fact that this is a very dispersed area, with a very low economic and education level, complicates the issues. Added to these factors are legislation, administration, and control processes which are shown in their historical, technical, health, and economic aspects. Using systemic integration, the article describes how the inherent interests of each part directly or indirectly involved may be articulated to result in self-control. The same approach reveals also the potential conflicts. Some existent proposals are analyzed with regard to the extent to which they can work, given the described aspect.

Brazil↗
PubMed2001

Geographical miss during catheter-based intracoronary beta-radiation: incidence and implications in the BRIE study. Beta-Radiation In Europe.

OBJECTIVES: We sought to determine the incidence and causes of geographical miss (GM) and to evaluate its impact on edge restenosis after intracoronary beta-radiation therapy. BACKGROUND: Edge restenosis is a limitation of intracoronary beta-radiation therapy. Geographical miss is the situation in which the radiation source does not fully cover the injured segment and may lead to edge restenosis. METHODS: We analyzed 175 vessels treated according to the Beta-Radiation In Europe (BRIE) study protocol. The effective irradiated segment (EIRS) and both edges were studied with quantitative coronary angiography. The edges of the EIRS that were injured constituted the GM edges. Restenosis was defined as diameter stenosis >50% at follow-up. Geographical miss was determined by simultaneous electrocardiographic-matched, side-by-side projection of the source and balloons deflated at the injury site, in identical angiographic projections surrounded by contrast. RESULTS: Geographical miss affected 41.2% of the edges and increased edge restenosis significantly compared with non-GM edges (16.3% vs. 4.3%, respectively, p = 0.004). Restenosis was increased both in the proximal (p = 0.05) and distal (p = 0.02) GM edges compared with noninjured edges. Geographical miss associated with stent injury significantly increased edge restenosis (p = 0.006), whereas GM related to balloon injury did not significantly increase edge restenosis (p = 0.35). The restenosis in the EIRS was similar between vessels with and without GM (24.3% and 21.6%, respectively, p = 0.8). CONCLUSIONS: Geographical miss is strongly associated with restenosis at the edges of the EIRS. This effect is more prominent when caused by stenting. Geographical miss does not increase restenosis in the EIRS.

Adult↗
PubMed2001

Effects of L-arginine and furosemide on blood pressure and renal function in volume-expanded rats.

1. The aim of the present study was to investigate the effects of L-arginine (L-Arg) on blood pressure and water and electrolyte excretion in control and extracellular fluid volume-expanded rats (10% bodyweight with 0.9% NaCl) and to determine whether diuretic treatment with furosemide (FUR) can be optimized by the administration of L-Arg in this model. 2. Both groups of animals were anaesthetized, divided into groups and treated with either 7.5 mg/kg FUR, 250 mg/kg L-Arg, 1 mg/kg NG-nitro-L-arginine methyl ester (L-NAME), FUR + L-NAME or FUR + L-Arg. Mean arterial pressure (MAP), diuresis, natriuresis and kaliuresis were determined. 3. Extracellular fluid volume expansion induced no changes in MAP in control and volume-expanded rats (92+/-6 vs 100+/-8 mmHg, respectively). The hypotension induced by FUR in control and volume-expanded rats (69+/-7 and 76+/-5 mmHg, respectively) was significantly (P < 0.01) enhanced by the administration of L-Arg (54+/-3 and 64+/-3 mmHg, respectively). 4. Injection of L-NAME increased MAP and diminished diuresis, natriuresis and kaliuresis in both groups. 5. Furosemide-induced water and electrolyte excretion was blunted by the administration of L-NAME. 6. The combination of L-Arg + FUR increased diuresis induced by FUR alone (control rats: 29.33+/-1.68 vs 12.91+/- 0.41 microL/min per 100 g, respectively; volume-expanded rats: 248.5+/-25.4 vs 112,6+/-8.3 microL/min per 100 g, respectively; P < 0.01). 7. The administration of the combination of L-Arg + FUR promoted a decrease in the sodium/water excretion ratio compared with the administration of FUR alone (control rats: 0.230+/-0.018 vs 0.45+/-0.03, respectively, P < 0.001; volume-expanded rats: 0.091+/-0.010 vs 0.22+/-0.03, respectively, P < 0.01). 8. The potassium/water excretion rate induced by FUR alone and in the presence of L-Arg followed a pattern similar to that seen for natriuresis (control rats: 0.35+/-0.05 vs 0.20+/-0.05 microEq/min per 100 g, respectively; volume-expanded rats: 0.045+/-0.008 vs 0.014+/-0.003 microEq/min per 100 g, respectively; P < 0.01). 9. The decrease in the electrolyte/water excretion ratio observed with FUR + L-Arg in volume-expanded rats was greater than in control animals. 10. The results of the present study show that the administration of FUR with L-Arg contributes to enhanced hypotensive and diuretic effects of FUR, thus diminishing the relative electrolyte excretion in normal conditions and in extracellular fluid volume expansion.

Animals↗
PubMed2001

Indirect evidence for a role of a subpopulation of activated neutrophils in the remodelling process after percutaneous coronary intervention.

AIM: Leukocytes have been implicated in restenosis following percutaneous transluminal coronary angioplasty. We investigated the link between the activated status of circulating neutrophils and restenosis after angioplasty. METHODS AND RESULTS: The population of 108 patients with single, de novo lesions located in native coronary arteries were treated with elective balloon angioplasty (n=44) or stenting (n=64). Pre-, post-procedure and 6-month follow-up, angiograms were analysed by an independent core laboratory. Blood samples were collected immediately before treatment and the antigen CD66, which is specifically expressed by activated neutrophils, was measured. Overall, the average expression of CD66 was 6.4+/-3.6 of mean fluorescence intensity. In the stepwise linear regression model, which included biological, clinical and angiographic variables, absolute gain showed a direct association (P<0.001) with relative late loss (relative late loss=absolute late loss/pre-procedure reference diameter), whereas CD66 expression was inversely associated with relative late loss (P=0.004). CD66 expression also showed an inverse association with relative late loss in the balloon angioplasty treated patients (P=0.002, beta=-0.49). In the stent subgroup, only reference vessel diameter and acute gain were independent predictors of relative late loss. CONCLUSION: Our results confirm the beneficial role of activated neutrophils pre-procedure in the restenotic process after balloon angioplasty. The lack of a relationship between CD66 expression by neutrophils and relative late loss after stenting suggests that this leukocyte may be involved in the remodelling process.

Angioplasty, Balloon, Coronary↗
PubMed2001

Glutathione-induced conversion of pentavalent antimony to trivalent antimony in meglumine antimoniate.

The standard treatment of human leishmaniases involves the use of pentavalent antimony [Sb(V)] compounds, including meglumine antimoniate. The mode of action of these compounds has not been fully elucidated. The possibility that Sb(III) is involved has been suggested; however, the biomolecule that may induce the conversion of Sb(V) to Sb(III) has not yet been identified. In the present study, we investigated both the ability of reduced glutathione (GSH) to promote the reduction of Sb(V) into Sb(III) in meglumine antimoniate and the effects of pH and temperature on this transformation. GSH did promote the reduction of Sb(V) into Sb(III) in a dose-dependent manner. When GSH and meglumine antimoniate were incubated together at a GSH/Sb molar ratio superior or equal to 5:1, all antimony was encountered in the reduced form, indicating a stoichiometry of 5:1 between GSH and Sb(V) in the reaction. The reaction between Sb(V) and GSH was favored at an acidic pH (pH 5) and an elevated temperature (37 degrees C), conditions found within the phagolysosome, in which Leishmania resides. For instance, about 30% of the Sb(V) (concentration, 2mM) was converted to Sb(III) following incubation for 3 days with 10 mM GSH at pH 5 and 37 degrees C. Our data support the hypothesis that Sb(V) would be converted by GSH, or a related thiol compound, to more toxic Sb(III) in the phagolysosome of macrophages.

Antimony↗
PubMed2001

Three dimensional intravascular ultrasonic assessment of the local mechanism of restenosis after balloon angioplasty.

OBJECTIVE: To assess the mechanism of restenosis after balloon angioplasty. DESIGN: Prospective study. PATIENTS: 13 patients treated with balloon angioplasty. INTERVENTIONS: 111 coronary subsegments (2 mm each) were analysed after balloon angioplasty and at a six month follow up using three dimensional intravascular ultrasound (IVUS). MAIN OUTCOME MEASURES: Qualitative and quantitative IVUS analysis. Total vessel (external elastic membrane), plaque, and lumen volume were measured in each 2 mm subsegment. Delta values were calculated (follow up - postprocedure). Remodelling was defined as any (positive or negative) change in total vessel volume. RESULTS: Positive remodelling was observed in 52 subsegments while negative remodelling occurred in 44. Remodelling, plaque type, and dissection were heterogeneously distributed along the coronary segments. Plaque composition was not associated with changes in IVUS indices, whereas dissected subsegments had a greater increase in total vessel volume than those without dissection (1.7 mm(3) v -0.33 mm(3), p = 0.04). Change in total vessel volume was correlated with changes in lumen (p < 0.05, r = 0.56) and plaque volumes (p < 0.05, r = 0.64). The site with maximum lumen loss was not the same site as the minimum lumen area at follow up in the majority (n = 10) of the vessels. In the multivariate model, residual plaque burden had an influence on negative remodelling (p = 0.001, 95% confidence interval (CI) -0.391 to -0.108), whereas dissection had an effect on total vessel increase (p = 0.002, 95% CI 1.168 to 4.969). CONCLUSIONS: The mechanism of lumen renarrowing after balloon angioplasty appears to be determined by unfavourable remodelling. However, different patterns of remodelling may occur in individual injured coronary segments, which highlights the complexity and influence of local factors in the restenotic process.

Angioplasty, Balloon, Coronary↗
PubMed2001

A phase II trial of fractionated vinorelbine/doxorubicin as first-line therapy for advanced breast cancer.

In western countries breast cancer is still the leading cause of death of women. Very promising results have been obtained by combining vinorelbine and doxorubicin, two of the most active drugs in metastatic breast cancer. However, despite the activity reported, this combination has shown a 10% rate of grade 2-4 cardiac toxicity, mainly due to the total cumulative doses of anthracycline delivered. The aim of this study was to divide the total dose of doxorubicin into two administrations on days 1 and 8, in order to cut down its toxicity while maintaining the same activity. Fifty-two chemotherapy naïve patients with metastatic breast cancer entered into the study and were treated with vinorelbine 25 mg/m2 plus doxorubicin 25 mg/m2 both on days 1 and 8 every three weeks. Fifty-one patients were eligible and evaluable for toxicity while 47 of them were evaluable for activity. Haematological toxicity was predominantly related to neutropenia, with grade 3/4 in 16% of cycles. Non-haematological toxicity was represented by alopecia grade 3 (which affected 65% of the patients), local phlebitis and severe constipation. No clinically significant cases of neuropathy or cardiac dysfunction were seen. With regard to activity, 38 out of 47 patients (80%) responded to therapy, nine of them achieving complete responses (19%). Median response duration was 16 months and the median overall survival was 22.7 months. We conclude that the fractionated administration of vinorelbine and doxorubicin is associated with excellent haematological and non-haematological tolerability (especially as regards cardiac toxicity), coupled with high levels of activity comparable to those observed using regimens based on unfractionated administration of treatment.

Alopecia↗
PubMed2001

Genetic and cytological characterization of a developmental mutant of Aspergillus nidulans induced by 5-azacytidine.

An analysis of a new medusa mutant of Aspergillus nidulans obtained by 5-azacytidine-treatment and named B116 is provided. The B116 mutant was phenotypically characterized by the production of conidiophores with reduced pigmentation and vesicles bearing multiple tiers of sterigmata. A single nuclear gene located on chromosome I is responsible for phenotypical changes in the mutant. The 5-azacytidine-altered locus, designated medA102, is recessive in heterozygous diploid and the medusa mutant is a Dp(II,I) duplication bearer that renders the strain mitotically unstable.

Alleles↗
PubMed2000

Methodological and clinical implications of the relocation of the minimal luminal diameter after intracoronary radiation therapy. Dose Finding Study Group.

OBJECTIVES: The aims of the study were to determine the incidence of relocation of the minimal luminal diameter (MLD) after beta-radiation therapy following balloon angioplasty (BA) and to describe a new methodological approach to define the effect of brachytherapy on treated coronary stenoses. BACKGROUND: Luminal diameter of coronary lesions may increase over time following angioplasty and irradiation. As a result, the MLD at follow-up may be relocated from its location preintervention, which may induce misleading results when a restricted definition of the target segment by quantitative coronary angiography (QCA) is performed. METHODS: Patients treated with BA followed by intracoronary brachytherapy according to the Dose-Finding Study constituted the study population. A historical cohort of patients treated with BA was used as control group. To be included in the analysis, an accurate angiographic documentation of all instrumentations during the procedure was mandatory. In the irradiated patients, four regions were defined by QCA: vessel segment (VS), target segment (TS), injured segment (INS), and irradiated segment (IRS). RESULTS: Sixty-five patients from the Dose-Finding Study and 179 control patients were included. At follow-up, MLD was relocated more often in the radiation group (78.5% vs. 26.3%; p < 0.0001). The rate of >50% diameter stenosis differed among the four predefined regions: 3.1% in the TS; 7.7% in the INS; 9.2% in the IRS and 13.8% in the VS. CONCLUSIONS: Relocation of the MLD is commonly demonstrated after BA and brachytherapy, and it should be taken into account during the analysis of the results of radiation clinical trials.

Angioplasty, Balloon↗
PubMed2000

Three-dimensional intravascular ultrasound assessment of noninjured edges of beta-irradiated coronary segments.

BACKGROUND: The "edge effect," late lumen loss at the margins of the treated segment, has become an important issue in the field of coronary brachytherapy. The aim of the present study was to assess the edge effect in noninjured margins adjacent to the irradiated segments after catheter-based intracoronary beta-irradiation. METHODS AND RESULTS: Fifty-three vessels were assessed by means of 3-dimensional intravascular ultrasound after the procedure and at 6- to 8-month follow-up. Fourteen vessels (placebo group) did not receive radiation (sham source), whereas 39 vessels were irradiated. In the irradiated group, 48 edges (5 mm in length) were identified as noninjured, whereas 18 noninjured edges were selected in the placebo group. We compared the volumetric intravascular ultrasound measurements of the noninjured edges of the irradiated vessels with the fully irradiated nonstented segments (IRS, n=27) (26-mm segments received the prescribed 100% isodose) and the noninjured edges of the vessels of the placebo patients. The lumen decreased (6 mm(3)) in the noninjured edges of the irradiated vessels at follow-up (P:=0. 001). We observed a similar increase in plaque volume in all segments: noninjured edges of the irradiated group (19.6%), noninjured edges of the placebo group (21.5%), and IRS (21.0%). The total vessel volume increased in the IRS in the 3 groups. No edge segment was subject to repeat revascularization. CONCLUSIONS: The edge effect occurs in the noninjured margins of radiation source train in both irradiated and placebo patients. Thus, low-dose radiation may not play an important role in this phenomenon, whereas nonmeasurable device injury may be considered a plausible alternative explanation.

Angioplasty, Balloon↗
PubMed2000

Positive geometric vascular remodeling is seen after catheter-based radiation followed by conventional stent implantation but not after radioactive stent implantation.

BACKGROUND: Recent reports demonstrate that intracoronary radiation affects not only neointimal formation but also vascular remodeling. Radioactive stents and catheter-based techniques deliver radiation in different ways, suggesting that different patterns of remodeling after each technique may be expected. METHODS AND RESULTS: We analyzed remodeling in 18 patients after conventional stent implantation, 16 patients after low-activity radioactive stent implantation, 16 patients after higher activity radioactive stent implantation, and, finally, 17 patients who underwent catheter-based radiation followed by conventional stent implantation. Intravascular ultrasound with 3D reconstruction was used after stent implantation and at the 6-month follow-up to assess remodeling within the stent margins and at its edges. Preprocedural characteristics were similar between groups. In-stent neointimal hyperplasia (NIH) was inhibited by high-activity radioactive stent implantation (NIH 9.0 mm(3)) and by catheter-based radiation followed by conventional stent implantation (NIH 6.9 mm(3)) compared with low-activity radioactive stent implantation (NIH 21.2 mm(3)) and conventional stent implantation (NIH 20.8 mm(3)) (P:=0.008). No difference in plaque or total vessel volume was seen behind the stent in the conventional, low-activity, or high-activity stent implantation groups. However, significant increases in plaque behind the stent (15%) and in total vessel volume (8%) were seen in the group that underwent catheter-based radiation followed by conventional stent implantation. All 4 groups demonstrated significant late lumen loss at the stent edges; however, edge restenosis was seen only in the group subjected to high-activity stent implantation and appeared to be due to an increase in plaque and, to a lesser degree, to negative remodeling. CONCLUSIONS: Distinct differences in the patterns of remodeling exist between conventional, radioactive, and catheter-based radiotherapy with stenting.

Adult↗
PubMed2000

Angiographic and clinical outcome of mild to moderate nonocclusive unstented coronary artery dissection and the influence on coronary flow velocity reserve. The Debate I Study Group.

Limited data are available regarding the angiographic healing rate and physiologic impact of coronary artery dissections. Therefore, we studied the impact of coronary dissections on coronary flow velocity and outcome as well as their healing rate at 6-month follow-up balloon angioplasty. Of 297 patients who underwent balloon angioplasty, 225 underwent intracoronary Doppler measurements and 184 had Doppler and angiographic assessment at 6-month follow-up. Dissections were scored by an independent core lab (Cardialysis BV) and divided in 4 groups: mild (types A to B), moderate (type C), severe (D to F), and patients without dissections. Severe dissections (types D to F) were excluded from the analysis. Clinical, angiographic, and Doppler data were compared among the remaining 3 patient groups. From the 67 dissections detected after balloon angioplasty, only 3 (4.5%) remained unhealed at follow-up. Immediately after balloon angioplasty, the moderate dissection group was associated with a lower coronary flow velocity reserve than the patients with mild (2.16 +/- 0.60 vs 2.82 +/- 1.00, p = 0.037) or no dissections (2.16 +/- 0.60 vs 2.71 +/- 0.88, p = 0.046), respectively. In addition, higher recurrence of angina at 30 days was observed in the moderate group rather than in the mild group (5 [50%] vs 8 [16%], p = 0.0160) and in the patients without dissections (11 [12%], p = 0.007). After standard balloon angioplasty, the occurrence of unhealed dissections is a rare phenomenon. An impaired coronary flow reserve was observed after the development of nonocclusive type C dissections, which was associated with a worse short-term outcome.

Angioplasty, Balloon, Coronary↗
PubMed2000

Geographic miss: a cause of treatment failure in radio-oncology applied to intracoronary radiation therapy.

BACKGROUND: A recognized limitation of endovascular beta-radiation therapy is the development of new stenosis at the edges of the irradiated area. The combination of injury and low-dose radiation may be the precursor of this phenomenon. We translated the radio-oncological concept of "geographic miss" to define cases in which the radiation source did not fully cover the injured area. The aims of the study were to determine the incidence and causes of geographic miss and evaluate the impact of this inadequate treatment on the outcome of patients treated with intracoronary beta-radiation. METHODS AND RESULTS: We analyzed 50 consecutive patients treated with beta-radiation after percutaneous coronary intervention. The prescribed dose ranged between 12 and 20 Gy at 2 mm from the source axis. By means of quantitative coronary angiography, the irradiated segment (IRS) and both edges were studied before and after intervention and at 6-month follow-up. Edges that were injured during the procedure constituted the geographic miss edges. Twenty-two edges were injured during the intervention, mainly because of procedural complications that extended the treatment beyond the margins of the IRS. Late loss was significantly higher in geographic miss edges than in IRSs and uninjured edges (0.84+/-0.6 versus 0.15+/-0.4 and 0.09+/-0.4 mm, respectively; P<0.0001). Similarly, restenosis rate was significantly higher in the injured edges (10% within IRS, 40.9% in geographic miss edges, and 1.9% in uninjured edges; P<0.001). CONCLUSIONS: These data support the hypothesis that the combination of injury and low-dose beta-radiation induces deleterious outcome.

Angioplasty, Balloon, Coronary↗
PubMed2000

Residual plaque burden, delivered dose, and tissue composition predict 6-month outcome after balloon angioplasty and beta-radiation therapy.

BACKGROUND: Inhomogeneity of dose distribution and anatomic aspects of the atherosclerotic plaque may influence the outcome of irradiated lesions after balloon angioplasty (BA). We evaluated the influence of delivered dose and morphological characteristics of coronary stenoses treated with beta-radiation after BA. METHODS AND RESULTS: Eighteen consecutive patients treated according to the Beta Energy Restenosis Trial 1.5 were included in the study. The site of angioplasty was irradiated with the use of a beta-emitting (90)Sr/(90)Y source. With the side branches used as anatomic landmarks, the irradiated area was identified and volumetric assessment was performed by 3D intracoronary ultrasound imaging after treatment and at 6 months. The type of tissue, the presence of dissection, and the vessel volumes were assessed every 2 mm within the irradiated area. The minimal dose absorbed by 90% of the adventitial volume (D(v90)Adv) was calculated in each 2-mm segment. Diffuse calcified subsegments and those containing side branches were excluded. Two hundred six coronary subsegments were studied. Of those, 55 were defined as soft, 129 as hard, and 22 as normal/intimal thickening. Plaque volume showed less increase in hard segments as compared with soft and normal/intimal thickening segments (P<0.0001). D(v90)Adv was associated with plaque volume at follow-up after a polynomial equation with linear and nonlinear components (r = 0.71; P = 0.0001). The multivariate regression analysis identified the independent predictors of the plaque volume at follow-up: plaque volume after treatment, D(v90)Adv, and type of plaque. CONCLUSIONS: Residual plaque burden, delivered dose, and tiss composition play a fundamental role in the volumetric outcome at 6-month follow-up after beta-radiation therapy and BA.

Angioplasty, Balloon, Coronary↗
PubMed2000

Three-dimensional intravascular ultrasonic volumetric quantification of stent recoil and neointimal formation of two new generation tubular stents.

Currently, several different designs of coronary stents are available. However, only a few of the new generation stents have been investigated in large randomized trials. Mechanical behavior of first-generation stents (Palmaz-Schatz, Gianturco-Roubin) may not be applied to the new designs. We investigated the chronic mechanical behavior (recoil) of 2 stents recently approved by the Food and Drug Administration (MULTILINK and NIR). Forty-eight patients with single-stent implantation (23 MULTILINK and 25 NIR) were assessed by means of volumetric 3-dimensional intravascular ultrasound analysis after the procedure and at 6-month follow-up. In addition, volumetric assessment of neointimal formation was performed. No significant chronic stent recoil was detected in both groups (delta MULTILINK stent volume: +5.6+/-41 mm3 [p = NS] and delta NIR stent volume + 2.1+/-26 mm3 [p = NS]). A similar degree of neointimal formation at 6 months was observed between the 2 stents (MULTILINK 46+/-31.9 mm3 vs NIR 39.9+/-27.6 mm3, p = NS). In conclusion, these 2 second-generation tubular stents did not show chronic recoil and appeared to promote similar proliferative response after implantation in human coronary arteries.

Cell Division↗
PubMed2000

Coronary bifurcation stenting using dedicated bifurcation stents.

We report three cases of successful implantation of three different stents specially designed for bifurcation lesions, guided by intracoronary ultrasound. The BARD and AVE are true bifurcated stents for side-branch access and the NIR-Side Royal is a single modified NIR stent with an aperture to allow provisional bifurcation stenting. These designs introduce a new era in percutaneous management of coronary bifurcation lesions. Cathet. Cardiovasc. Intervent. 49:105-111, 2000.

Adult↗
PubMed2000

Dirigent-mediated podophyllotoxin biosynthesis in Linum flavum and Podophyllum peltatum.

Given the importance of the antitumor/antiviral lignans, podophyllotoxin and 5-methoxypodophyllotoxin, as biotechnological targets, their biosynthetic pathways were investigated in Podophyllum peltatum and Linum flavum. Entry into their pathways was established to occur via dirigent mediated coupling of E-coniferyl alcohol to afford (+)-pinoresinol; the encoding gene was cloned and the recombinant protein subsequently obtained. Radiolabeled substrate studies using partially purified enzyme preparations next revealed (+)-pinoresinol was enantiospecifically converted sequentially into (+)-lariciresinol and (-)-secoisolariciresinol via the action of an NADPH-dependent bifunctional pinoresinol/lariciresinol reductase. The resulting (-)-secoisolariciresinol was enantiospecifically dehydrogenated into (-)-matairesinol, as evidenced through the conversion of both radio- and stable isotopically labeled secoisolariciresinol into matairesinol, this being catalyzed by the NAD-dependent secoisolariciresinol dehydrogenase. (-)-Matairesinol was further hydroxylated to afford 7'-hydroxymatairesinol, this being efficiently metabolized into 5-methoxypodophyllotoxin. Thus much of the overall biosynthetic pathway to podophyllotoxin has been established, that is, from the dirigent mediated coupling of E-coniferyl alcohol to the subsequent conversions leading to 7'-hydroxymatairesinol.

Amino Acid Sequence↗