Intra-amniotic digoxin for feticide between 21 and 30 weeks of gestation: a prospective study.

OBJECTIVE: Intra-amniotic injection of digoxin is a well-known method for feticide before inducing a termination of pregnancy (TOP) at 17-24 weeks of gestation. Information on its effectiveness when administered after 24 weeks of gestation is limited. This study evaluated the efficacy of intra-amniotic digoxin injection for inducing fetal demise within 18-24 hours, at 21-30 weeks of gestation, and its safety. DESIGN: Prospective cohort study. SETTING: Tertiary university medical centre. POPULATION: Women at 21-30 weeks of gestation with a singleton pregnancy, admitted for TOP. METHODS: Intra-amniotic injection of 2 mg of digoxin was performed 1 day before medical TOP. Fetal heart activity was evaluated by ultrasound for 18-24 hours after the injection. Serum digoxin level and maternal electrocardiogram (ECG) were evaluated 6, 10, and 20 hours after injection. MAIN OUTCOME MEASURE: Frequency of successful fetal demise. RESULTS: Fifty-nine women participated in the study. The mean gestational age was 24+2  weeks (range 21+0 -30+0 ), with 29 (49.2%) beyond 24+0  weeks of gestation. Fetal cardiac activity arrest was achieved in 55/59 cases (93.2%). Normal maternal ECG recordings were noted in all cases. Mean serum digoxin levels 6 and 10 hours after injection were in the therapeutic range (1.3 ± 0.7 ng/l and 1.24 ± 0.49 ng/l, respectively) and below the toxic level (2 ng/l). Extramural delivery following digoxin did not occur. There were no cases of chorioamnionitis. CONCLUSION: Intra-amniotic digoxin for feticide at 21-30 weeks of gestation in a singleton pregnancy appears effective and safe before TOP at advanced gestational ages. TWEETABLE ABSTRACT: This study shows that feticide by intra-amniotic digoxin injection at 21-30 weeks of gestation appears effective and safe.

Acne: a side-effect of masculinizing hormonal therapy in transgender patients.

BACKGROUND: Masculinizing hormonal treatment in transgender men has the potential to increase the level of androgens at end organs, including the pilosebaceous unit. Androgen-induced sebocyte growth and differentiation, sebum production and infundibular keratinization may underlie the development of acne vulgaris among patients receiving this therapy. OBJECTIVES: The aim of this article is to familiarize dermatologists with the sensitivities and challenges of treating acne in transgender male individuals. METHODS: This review article discusses the pathogenesis and treatment of acne in transgender men on testosterone therapy and highlights the unique considerations in treating this underserved patient population. RESULTS: Despite the incidence of treatment-related acne and the unique considerations in treating transgender men, studies addressing this topic among this patient population are limited. CONCLUSIONS: Generally, the standard guidelines for the treatment of acne can be followed in treating these patients; however, several medical, social and psychological factors should be considered.

Lichenoid vulvar disease: A review.

Vulvar dermatoses are common, potentially debilitating conditions that can be seen by a variety of medical specialists. Lichenoid vulvar diseases, namely lichen sclerosus (LS), lichen planus (LP), and lichen simplex chronicus (LSC), can all negatively impact patients' quality of life and LS and LP also have an association with squamous cell carcinoma. It is essential that dermatologists are familiar with the unique features of each of these conditions to ensure the appropriate management and follow up. Herein, we provide an update on the epidemiology, clinical presentation, histopathology, and treatment of patients with vulvar LS, LP, and LSC.

Papular acantholytic dyskeratosis of the vulva associated with familial Hailey-Hailey disease.

Papular acantholytic dyskeratosis (PAD) of the vulva is a rare, chronic disorder first described in 1984. It presents in young women as white to skin-coloured smooth papules over the vulva, which are persistent but asymptomatic. Histologically, there is hyperkeratosis and focal parakeratosis with acantholytic and dyskeratotic cells forming corps ronds and grains, placing PAD within Ackerman's spectrum of focal acantholytic dyskeratoses with Hailey-Hailey disease (HHD) and Darier disease. There have been 17 previous reports of PAD of the vulva, to our knowledge. Only one demonstrated a familial pattern, and none of the cases was associated with a family history of HHD. This is the first report of PAD and HHD in a single family, suggesting that PAD and HHD lie on a spectrum of disease and are genetically linked.

First trimester human placental factors induce breast cancer cell autophagy.

Placental factors, progesterone included, facilitate breast cancer cell line (BCCL) motility and thus may contribute to the advanced breast cancer found during pregnancy. Cancer and placental implantations are similar; the last is accompanied by extravillous trophoblast cell invasion and autophagy which are interlinked. We aimed to analyze the effect of first trimester human placenta on BCCL autophagy. BCCLs (MCF-7/T47D) were cultured with placental explants (60 h) or placental supernatants (24 h). Following cultures, BCCLs were sorted out for RNA/protein extraction. RNA served for microarray/qPCR (BNIP3) and protein for Western blot (HIF1α, LC3BII) analyses. Inhibitors were added to the placenta-MCF-7 coculture or placental supernatants (autophagy inhibitor-3MA, progesterone receptor (PR) inhibitor-RU486, and HIF1α inhibitor-Vitexin) in order to evaluate their effects on BCCL motility and LC3BII/HIF1α expression. LC3BII (an autophagy marker) expression was elevated in BCCLs following placental explant coculture and exposure to placental supernatants. The autophagy inhibitor (3MA) repressed the placenta-induced MCF-7/T47D migration, establishing a connection between BCCL autophagy and migration. Microarray analysis of MCF-7 following placenta-MCF-7 coculture showed that "HIF1α pathway," a known autophagy facilitator, was significantly manipulated. Indeed, placental factors elevated HIF1α and its target BNIP3 in the BCCLs, verifying array results. Lastly, PR inhibitor reduced HIF1α expression and both PR and HIF1α inhibitors reduced MCF-7 LC3BII expression and motility, suggesting involvement of the PR-HIF1α axis in the autophagy process. Placental factors induced BCCL autophagy that is interlinked to their motility. This suggests that autophagy-related molecules may serve as targets for therapy in pregnancy-associated breast cancer.

The effect of heat shock protein 27 on extravillous trophoblast differentiation and on eukaryotic translation initiation factor 4E expression.

Heat shock protein (HSP27) is expressed in human placentae. Previously, we showed that HSP27 is expressed in the villous cell column of first trimester placental explants and in extravillous trophoblast (EVT) cells. EVT differentiation is accompanied by increased motility, matrix metalloproteinase (MMP) activity, decreased proliferation and expression of specific markers such as HLAG and CD9. HSP27 regulates cell apoptosis, migration, protein stability and the availability of eukaryotic translation initiation factors, such as eukaryotic translation initiation factor 4E (eIF4E). eIF4E supports trophoblast cell proliferation and survival. We wanted to explore the effect of HSP27 silencing on trophoblast cell phenotype, EVT markers and eIF4E expression and regulators [4E-binding protein (4E-BP1) and MAP kinase-interacting kinase (MNK1)]. This study evaluated the effect of HSP27 siRNA on placental explant and HTR-8/SVneo migration, MMP activity/mRNA, cell death, cell cycle, HLAG/CD9 levels, and eIF4E and its regulators' total and phosphorylated levels. Furthermore, we evaluated HSP27 levels in placentae exposed to ribavirin, which triggers EVT differentiation. We found that HSP27 silencing increased cell death in HTR-8/SVneo and placental explants. Furthermore, it reduced HTR-8/SVneo migration and EVT outgrowth from the explants (P < 0.05), MMP2 activity and expression of EVT markers HLAG and CD9 (in placental explants and HTR-8/SVneo, respectively, P < 0.05). Induction of EVT differentiation by ribavirin elevated HSP27 levels. Finally, HSP27 silencing in both HTR-8/SVneo and placental explants reduced eIF4E levels (33 and 28%, respectively, P < 0.05) and the levels of its regulators 4E-BP1 and MNK1 (37 and 32%, respectively, done on HTR-8/SVneo only), but not their phosphorylated forms. Altogether, our results suggest that HSP27 contributes to EVT cell differentiation.

The involvement of eukaryotic translation initiation factor 4E in extravillous trophoblast cell function.

UNLABELLED: Extravillous trophoblast cells (EVT) are major players in placental implantation. They differentiate in the villous cell column, invade to the uterus and remodel the uterine spiral arteries. Trophoblast and tumor cells have similar invasion mechanisms, share similar biochemical mediators (e.g. c-myc, MMP9) and growth-factors (e.g. VEGF). The mRNA of these proteins has extremely structured 5-UTR and their translation is highly dependent on eukaryotic-translation-initiation-factor-4E (eIF4E). Cancer cells have elevated eIF4E and are more vulnerable to its silencing than normal cells. We speculated that like cancer, trophoblast function is highly eIF4E dependent. OBJECTIVE: Analyze eIF4E involvement in EVT differentiation and function. STUDY DESIGN: EIF4E levels were assessed in first-trimester human placentae and in placental explants before and after EVT differentiation. The effect of eIF4E knockdown (siRNA, ribavirin) on the phenotype of placental explant and EVT cell lines (HTR-8/SVNEO) was evaluated. Tested parameters included eIF4E and its target levels, migration, invasion, cell death, cell cycle and cell count. RESULTS: High eIF4E levels were found in cytotrophoblast and especially EVT cells during their differentiation in the villi, compared to other placental cell types. EIF4E silencing increased cell death and cell cycle arrest in placental explants and HTR-8/SVNEO cells. Although it induced EVT outgrowth in the placental explants, it reduced HTR-8/SVNEO motility, reflecting the importance of using ex vivo models that include an intact placental microenvironment in its original architecture. CONCLUSIONS: Our results suggest that eIF4E prevents final EVT differentiation and supports placental cell proliferation and survival. A balance between cell proliferation and differentiation is crucial for placental development and implantation.

Hormone-dependent placental manipulation of breast cancer cell migration.

BACKGROUND: Breast cancer during pregnancy is often more advanced than in non-pregnant women. Nevertheless, no case of metastasis inside the placenta has been reported. Previously, we showed that placental-explants eliminated breast cancer cells from their surroundings, due to cell-death and elevated migration. Our objective was to find the underlying mechanisms of these phenomena. METHODS AND RESULTS: Our model contained Michigan Cancer Foundation 7 (MCF7) or T47D cells co-cultured with and without human placental explants. Microarray analysis, validated by quantitative PCR, of MCF7 following their placental co-culture suggested activation of estrogen (E(2)) signaling. As extensive cross-talk exists between E(2) and progesterone, their involvement in mediating placental effects on breast cancer cells was tested. Indeed, addition of E(2) and progesterone receptor (ER and PR) inhibitors to the co-culture system reduced cancer cell motility, yet did not alter cell-cycle or death. E(2) and progesterone concentrations in placental media were found to be similar to those of early pregnancy blood levels. Interestingly, placental-breast cancer co-culture media contained lower progesterone (P < 0.05) and higher E(2) (200%, P < 0.05) levels than placentae cultured separately. Placental supernatant and E(2) and progesterone at placental levels were sufficient to increase MCF7 and T47D migration and invasion (P < 0.05), yet did not alter MCF7 cell-cycle or death. Furthermore, placental supernatant elevated p38 and Jun N-terminal kinase (JNK) phosphorylation in both cell lines (P < 0.05). Inhibitors of JNK, ER and PR reversed MCF7 and T47D motility induced by the placenta, suggesting their involvement. CONCLUSIONS: We suggest that E(2) and progesterone contribute to cell migration away from placental areas. We hypothesize that they may increase metastatic spread to other organs in pregnancy.

Breast cancer characteristics are modified by first trimester human placenta: in vitro co-culture study.

BACKGROUND: Pregnant women with breast cancer present with a more advanced disease compared with non-pregnant women. Nevertheless, breast cancer metastasis to the placenta is rare. Trophoblast/tumor implantations share the same biochemical mediators, while only the first is stringently controlled. We hypothesized that the same mechanisms that affect/restrain placental implantation may inhibit metastatic growth in the placenta. We aimed to analyze the effects of human placenta on breast cancer cells. METHODS: First trimester human placental explants were co-cultured with MCF-7/T47D-eGFP tagged cells. Following culture, placenta/cancer cells/both were fixed, paraffin embedded and sliced for immunohistochemical analysis or sorted by their eGFP expression for future analysis. The tested parameters were: proliferation (immunohistochemistry)/cell cycle (FACS), apoptosis (immunohistochemistry/FACS), cell count/adhesion/distribution around the placenta (cell sorter, visual observation and counting), matrix metalloproteinase activity (zymogram) and estrogen receptor (ER) expression (western blotting, immunohistochemistry). RESULTS: Reduced breast cancer cell numbers (45%↓, 48%↓ for MCF-7/T47D, respectively, P < 0.05) were observed near the placenta. The placenta elevated MCF-7 sub-G1 phase and modestly elevated apoptosis (3-17%↑ for T47D/MCF-7, respectively, P < 0.05). Our findings demonstrate breast cancer cell migration from the placenta as: (i) T47D/MCF-7 cells changed their morphology to that of motile cells; (ii) elevated MMPs activity was found in the co-culture; (iii) placental soluble factors detached breast cancer cells; and (4) the placenta reduced MCF-7/T47D cells' ER expression (a characteristic of motile cells). CONCLUSIONS: MCF-7/T47D cells are eliminated from the placental surroundings. Analyzing the causes of these phenomena may suggest biological pathways for this event and raise new therapeutic targets.

Impaired migration of trophoblast cells caused by simvastatin is associated with decreased membrane IGF-I receptor, MMP2 activity and HSP27 expression.

BACKGROUND: Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme-A reductase, the rate-limiting enzyme of the mevalonate pathway, and are used successfully in the treatment of hypercholesterolaemia. Statins are contraindicated during pregnancy. Lately, we have shown that simvastatin has adverse affects on human first trimester placental explants' proliferation and migration. The objective of the present study was to investigate the molecules involved in mediating simvastatin's effect on trophoblast cell migration. We hypothesized that simvastatin attenuates insuline-like growth factor-I (IGF-I) receptor expression (involved in trophoblast motility), matrix metalloproteinase (MMP) activities, and heat shock protein 27 (HSP27) levels (whose mRNA is actively transcribed during trophoblast differentiation) in trophoblast cells thus consequently effecting their migration. METHODS: Human placental explants were cultured above a matrigel with/without simvastatin (10 microM) for 5 days. In this model, trophoblast migrates from the villi into the matrigel. Western-blot and immunohistochemistry served for analysing HSP27 expression. Immunohistochemistry was used for assessing IGF-I receptor localization. MMPs activity was assayed by gel zymography. RESULTS: Simvastatin reduced IGF-I receptor membranal expression, MMP2 activity and HSP27 expression in trophoblast cells (P < 0.05). CONCLUSIONS: The inhibitory effect of simvastatin on trophoblast cell migration is associated with a significant decrease in the tested molecules, which probably contributes to the impaired migration.

Simvastatin has deleterious effects on human first trimester placental explants.

BACKGROUND: Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMG-CoA reductase), the rate-limiting enzyme of the mevalonate pathway, and have been used successfully in the treatment of hypercholesterolaemia. Animal models have provided evidence for the teratogenic effects of statins on pregnancy outcome. Thus statins are contraindicated during pregnancy. However, conflicting data are available from inadvertent use of statins in human pregnancy. Therefore we decided to explore the effects of simvastatin on the placenta in an in vitro human placental model. METHODS: Human first trimester placental explants that were grown on matrigel were exposed to medium supplemented with simvastatin. Migration of extravillous trophoblast cells was assessed by visual observation. Proliferative and apoptotic events of the trophoblast cells were assesed by immunohistochemical examination using anti-Ki67 and anti-activated caspase-3 antibodies respectively. Hormone levels were measured. RESULTS: Simvastatin sharply inhibited migration of extravillous trophoblast cells from the villi to the matrigel (P < 0.05). Moreover, simvastatin inhibited half of the proliferative events in the villi (P < 0.05) and increased apoptosis of cytotrophoblast cells compared to control. Moreover, simvastatin significantly decreased secretion of progesterone from the placental explants (P < 0.01). CONCLUSION: Simvastatin adversely affects human first trimester trophoblast.

Signal transduction pathways involved in soluble fractalkine-induced monocytic cell adhesion.

Fractalkine displays features that distinguishes it from the other chemokines. In particular, besides its chemoattractant action it promotes, under physiologic flow, the rapid capture and the firm adhesion of a subset of leukocytes or intervenes in the neuron/microglia interaction. This study verified that indeed the human monocytic MonoMac6 cell line adheres to fibronectin-coated filters in response to soluble fractalkine (s-FKN). s-FKN stimulates, with distinct time courses, extracellular signal-related kinases (ERK1 and ERK2) and stress-activated protein kinases (SAPK1/JNK1 and SAPK2/p38). Both p60 Src and p72 Syk were activated under s-FKN stimulation with a rapid kinetic profile compatible with a downstream regulation on the mitogen-activated protein kinase (MAPK) congeners. The use of specific tyrosine kinase inhibitors revealed that the ERK pathway is strictly controlled by Syk, whereas c-Src up-regulated the downstream SAPK2/p38. In contrast, the SAPK1/JNK1 pathway was not regulated by any of these nonreceptor tyrosine kinases. The s-FKN-mediated increased adherence of MonoMac6 cells was partially inhibited by SB202190, a broad SAPKs inhibitor, PD98059, an MEK inhibitor, LY294002, a phosphatidyl inositol 3-kinase inhibitor, and a pertussis toxin-sensitive G protein. These data highlight that the integration of a complex array of signal transduction pathways is necessary to complete the full s-FNK-dependent adherence of human monocytic cells to fibronectin. (Blood. 2001;97:2031-2037)

Signal transduction involved in MCP-1-mediated monocytic transendothelial migration.

Monocyte chemoattractant protein-1 (MCP-1) is a major chemoattractant for monocytes and T lymphocytes. The MonoMac6 cell line was used to examine MCP-1 receptor-mediated signal transduction events in relation to MCP-1-mediated monocytic transendothelial migration. MCP-1 stimulates, with distinct time courses, extracellular signal-related kinases (ERK1 and ERK2) and stress-activated protein kinases (SAPK1/JNK1 and SAPK2/p38). SAPK1/JNK1 activation was blocked by piceatannol, indicating that it is regulated by Syk kinase, whereas SAPK2/p38 activation was inhibited by PP2, revealing an upstream regulation by Src-like kinases. In contrast, ERK activation was insensitive to PP2 and piceatannol. Pertussis toxin, a blocker of Go/Gi proteins, abrogated MCP-1-induced ERK activation, but was without any effect on SAPK1/JNK1 and SAPK2/p38 activation. These results underscore the major implication of Go/Gi proteins and nonreceptor tyrosine kinases in the early MCP-1 signaling. Furthermore, MCP-1-mediated chemotaxis and transendothelial migration were significantly diminished by a high concentration of SB202190, a broad SAPK inhibitor, or by SB203580, a specific inhibitor of SAPK2/p38, and abolished by pertussis toxin treatment. Altogether, these data suggest that coordinated action of distinct signal pathways is required to produce a full response to MCP-1 in terms of monocytic locomotion.

Effect of saline irrigation flow rate on temperature profile during cooled radiofrequency ablation.

INTRODUCTION: Cooled radiofrequency ablation has been developed clinically for the treatment of ventricular tachycardia. Although clinical studies employ a constant saline flow rate for cooling, we hypothesized that varying the flow rates might optimize the temperature profile at depth. METHODS: In excised ovine left ventricle, we compared the temperature profile from a catheter tip electrode thermocouple to those placed at depths of 0.0 mm, 1.0 mm, and 2.0 mm. We compared the following settings: 20 Watts without flow, 20 Watts with 0.3 cc/sec flow, 20 Watts with 0.5cc/sec flow, and 70C surface temperature without flow (temperature control). RESULTS: The temperatures decreased from 77.5 +/-10.5 degrees C, 91.7+/-6.3 degrees C, 65.5 +/- 11.8 degrees C, and 52.5 +/- 11.8 degrees C at 20W without saline irrigation at the tip, 0.0mm, 1.0mm, and 2.0 mm, respectively, to 33.0+/-1.4 degrees C, 63.4 +/- 7.0 degrees C, 57.1+/-5.8 degrees C, 49.9+/-5.8 degrees C+ at 20W with 0.5 ml/sec flow (*p<0.01, +p = 0.09). The lesion volumes were 79.6mm3 for 20W without flow, 64.1 mm3 for 20W with 0.3 ml/sec flow, 47.5 mm3 for 20W with 0.5 ml/sec flow, and 28.6 mm3 for temperature control. CONCLUSIONS: We conclude that 1) the temperature profile greatly depends upon the rate of saline flow for cooling; 2) at high flow rates, the 0.0 mm and 1.0 mm temperatures are similar; 3) even at high irrigation rates, lesion size is greater than for temperature control; 4) the tip temperature significantly underestimates the surface temperature and improved methods of measuring temperature are needed.

Effect of saline irrigation flow rate on temperature profile during cooled radiofrequency ablation

Introduction: Cooled radiofrequency ablation has been developed clinically for the treatment of ventricular tachycardia. Although clinical studies employ a constant saline flow rate for cooling, we hypothesized that varying the flow rates might optimize the temperature profile at depth.Methods: In excised ovine left ventricle, we compared the temperature profile from a catheter tip electrode thermocouple to those placed at depths of 0.0 mm, 1.0 mm, and 2.0 mm. We compared the following settings: 20 Watts without flow, 20 Watts with 0.3 cc/sec flow, 20 Watts with 0.5 cc/sec flow, and 70 degrees C surface temperature without flow (temperature control).Results: The temperatures decreased from 77.5+/-10.5 degrees C, 91.7+/-6.3 degrees C, 65.5+/-11.8 degrees C, and 52. 5+/-11.8 degrees C at 20 W without saline irrigation at the tip, 0.0 mm, 1.0 mm, and 2.0 mm, respectively, to 33.0+/-1.4 degrees C*, 63. 4+/-7.0 degrees C*, 57.1+/-5.8 degrees C*, 49.9+/-5.8 degrees C+ at 20 W with 0.5 ml/sec flow (*P<0.01, +P=0.09). The lesion volumes were 79.6 mm(3) for 20 W without flow, 64.1 mm(3) for 20 W with 0.3 ml/sec flow, 47.5 mm(3) for 20 W with 0.5 ml/sec flow, and 28.6 mm(3) for temperature control.Conclusions: We conclude that 1) the temperature profile greatly depends upon the rate of saline flow for cooling; 2) at high flow rates, the 0.0 mm and 1.0 mm temperatures are similar; 3) even at high irrigation rates, lesion size is greater than for temperature control; 4) the tip temperature significantly underestimates the surface temperature and improved methods of measuring temperature are needed.

Electrophysiological correlates of transmural linear ablation.

The purpose of this study is to describe the characteristics of lesions created using radiofrequency (RF) energy delivered through a saline/foam electrode that is designed to simplify ablation of the isthmus between the tricuspid annulus (TA) and the inferior vena cava (IVC). We compared the changes in the electrophysiological parameters produced by the ablation to histological findings. In search of a more practical and effective atrial flutter ablation method, various energy modifications and catheter designs have been tested. It was shown that the efficiency of RF ablation could be improved using an endocardial cooled catheter; resulting in increased lesion size. Thus, we postulate that a similar advantage of the cooled catheter system would allow efficient RF delivery through specially designed long foam electrodes, therefore improving the practicality of TA-IVC isthmus ablation for atrial flutter. The study was performed in two acute and five subacute sheep under general anesthesia and with adequate heparinization. We used a linear ablation catheter system equipped with two 2-cm saline bipole electrode pockets with 1.5-mm separation, each consisting of two 8-mm electrodes with 1-mm spacing, allowing for bipolar pacing and recording. This saline/foam electrode pair were positioned on a support loop. RF energy was applied to the saline electrodes at 50 watts for 90 seconds with a saline flow rate of 0.4 mL/s. Bipolar atrial signal amplitude and pacing thresholds were measured before and after ablation. If necessary, the catheter was pulled back and additional ablation was applied to any viable tissue. Transisthmus ablations were created with a single catheter positioning in five sheep using both saline electrodes in four and one electrode in the other. Pullback and additional ablation to one saline electrode was required in two sheep; in one after RF was delivered to only one electrode. After ablation, atrial signal amplitude was reduced by an average of 76% (range 51%-92%) and its pacing threshold was increased by an average of 617% (range 150%-400%). Transmural lesions were found in all sheep, measuring 8-20 mm in length, 4-10 mm in width, and 1.5-2.0 mm in depth. No charring, coagulum, or remote structural damage was found in any preparation. Continuous transmural TA-IVC isthmus lesions could be produced with stationary RF linear ablation using a saline/foam electrode catheter system. This system allowed for assessment of electrophysiological parameters that correlated with complete necrosis.

Rediscovering mycophenolic acid: a review of its mechanism, side effects, and potential uses.

Oral mycophenolic acid (MPA) therapy has been investigated in the treatment of moderate to severe psoriasis since the early 1970s and has been found to be both safe and effective. By inhibiting de novo purine biosynthesis, it functions as an antifungal, antibacterial, antiviral, and immunosuppressive agent. The recent availability of mycophenolate mofetil (MMF), a morpholinoester of MPA, has created renewed interest in the antipsoriatic properties of MPA. MMF is currently indicated for the prevention of organ rejection in transplant recipients and is used concomitantly with cyclosporine and corticosteroids. This review focuses on the pharmacology of MPA and MMF, studies of MPA in the treatment of psoriasis, and therapy with MMF. There is a potential application of MMF in the treatment of severe psoriasis and other inflammatory dermatoses, as well as topical MPA for the treatment of psoriasis.