Protective effect of quercetin on histomorphometric changes in kidney of retinoid acid-treated rat fetuses / Efecto protector de la quercetina sobre los cambios histomorfométricos en el riñón de fetos de rata tratados con ácido retinoico

SUMMARY: Retinoic acid, an active metabolite of vitamin A, plays essential signaling roles in mammalian embryogenesis. Prenatal rat fetuse exposure to retinoid induces some malformations in various organs, the most active and teratogenic metablolite is all-transretinoic acid (atRA). The teratogenic effects of some drugs can be prevented by the application of antioxidant drugs and stimulation of the maternal immune system. Also, quercetin, a naturally occurring flavonoid has excellent antioxidant properties. Therefore, the aim of this study was assess the protective effects of quercetin against atRA in fetuses of rat's kidney tissue. This study was performed on 40 pregnant rats that were divided into seven groups. Control group received normal saline and test groups received DMSO, quercetin (75 mg/kg), quercetin (200 mg/kg), atRA (25 mg/kg), atRA (25 mg/kg) plus quercetin (75 mg/kg) and atRA (25 mg/kg) plus quercetin (200 mg/kg), intraperitoneally at 8-10th days of gestation. Fetuses were collected at 20th day of gestation. Kidneys were collected and placed in 10 % buffered formalin solution. Then, kidneys were sectioned by routine method and stained by H&E and examined histologically. On histomorphomertrical examination, it was observed the priglomerular space and diameter of renal corpuscle in group which received only atRA were significantly (p≤0.05) greater than those received normal saline, dimethyl sulfoxide and quercetin, while these two indexes in group which received atRA plus quercetin significantly (p≤0.05) decreased by quercetin as dose dependent manner. Number of renal corpuscles were significantly (p≤0.05) decreased by atRA, but the quercetin could not affect the glomerular numbers. It is concluded that quercetin can protect fetuses against atRA damages and prevent their incidence probably via its antioxidant effect.

RESUMEN: El ácido retinoico, un metabolito activo de la vitamina A, desempeña un papel esencial de señalización en la embriogénesis de mamíferos. La exposición al ácido retinoico en fetos de ratas prenatales induce malformaciones en varios órganos, siendo el metabolito más activo y teratogénico el ácido transretinoico (ATRA). Los efectos teratogénicos de algunos medicamentos se pueden prevenir mediante la aplicación de medicamentos antioxidantes y la estimulación del sistema inmune materno. Además, la quercetina, un flavonoide de origen natural, tiene excelentes propiedades antioxidantes. Por lo tanto, el objetivo de este estudio fue evaluar los efectos protectores de quercetina contra ATRA en fetos de tejido de riñón de rata. Este estudio se realizó en 40 ratas preñadas que se dividieron en siete grupos. El grupo control recibió solución salina normal y los grupos de prueba recibieron DMSO, quercetina (75 mg / kg), quercetina (200 mg / kg), ATRA (25 mg / kg), ATRA (25 mg / kg) más quercetina (75 mg / kg) y ATRA (25 mg / kg) más quercetina (200 mg / kg), por vía intraperitoneal a los 8-10 días de gestación. Los fetos se recolectaron a los 20 días de gestación. Los riñones se recogieron y se colocaron en solución de formalina tamponada al 10 %. Luego, los riñones se seccionaron por método de rutina y se tiñeron con H & E y se examinaron histológicamente. En el examen histomorfométrico, se observó que el espacio periglomerular y el diámetro del corpúsculo renal en el grupo que recibió solo ATRA fueron significativamente (p≤0.05) mayores que los que recibieron solución salina normal, dimetilsulfóxido y quercetina, mientras que estos dos índices, en el grupo que recibió ATRA más quercetina, disminuyó significativamente (p≤0.05) en forma dependiente de la dosis. El número de corpúsculos renales disminuyó significativamente (p≤0.05) por el ATRA, pero la quercetina no pudo afectar el número de glomérulos. Se concluye que la quercetina puede proteger a los fetos contra daños de ATRA y prevenir su incidencia, probablemente, a través de su efecto antioxidante.

Tretinoin peel: a critical view

Abstract The tretinoin peel, also known as retinoic acid peel, is a superficial peeling often performed in dermatological clinics in Brazil. The first study on this was published in 2001, by Cuce et al., as a treatment option for melasma. Since then, other studies have reported its applicability with reasonable methodology, although without a consistent scientific background and consensus. Topical tretinoin is used for the treatment of various dermatoses such as acne, melasma, scars, skin aging and non-melanoma skin cancer. The identification of retinoids cellular receptors was reported in 1987, but a direct cause-effect relation has not been established. This article reviews studies evaluating the use of topical tretinoin as agent for superficial chemical peel. Most of them have shown benefits in the treatment of melasma and skin aging. A better quality methodology in the study design, considering indication and intervention is indispensable regarding concentration, vehicle and treatment regimen (interval and number of applications). Additionally, more controlled and randomized studies comparing the treatment with tretinoin cream versus its use as a peeling agent, mainly for melasma and photoaging, are necessary.

Efecto de la administración de ácido retinoico sobre el desarrollo del esqueleto axial en embriones de ratón Mus musculus / Effect of administration of retinoic acid on the development of the axial skeleton in mouse embryos Mus musculus

El déficit y exceso de vitamina A provoca malformaciones congénitas que afectan distintos órganos y sistemas. El objetivo de este estudio fue determinar el efecto que causa la administración de ácido retinoico a distintas dosis sobre la morfogénesis ósea del esqueleto axial en embriones de ratón Mus musculus. Mediante aleatorización simple se distribuyeron hembras recién preñadas en 4 categorías: A, B, C y D. El día 8 post fecundación (p.f), se administró 40 mg/kg de peso de ácido retinoico al grupo A, 20 mg/kg de peso de esta solución al grupo B, 1 ml/kg de peso de dimetil sulfóxido al grupo C, y el grupo D es grupo control. El día 17 de la gestación las hembras y sus fetos fueron anestesiadas y eutanasiadas con sobredosis de pentotal sódico intraperitoneal. Los fetos de cada camada fueron procesados mediante diafanización y tinción con azul de Alcian para destacar cartílago hialino y alizarina para observar tejido óseo. Los resultados se expresaron en porcentajes de malformaciones en los siguientes tres segmentos: 1) cráneo-columna cervical, 2) segmento torácico y abdominal y 3) cintura pélvica, considerándose un 100% cuando la totalidad de los elementos óseos se encontraban comprometidos. Se utilizó la prueba de Fisher para la comparación de frecuencias de malformaciones y se consideró estadísticamente significativo cuando p<0,05. En el grupo A se evidenciaron malformaciones mayores como ausencia de huesos frontales y parietales, exencefalia, defectos en el número de vértebras, y fusiones de costillas; y en el grupo B se observaron malformaciones menores como alteraciones numéricas y fusiones de costillas, existiendo diferencias significativas entre ambos grupos. En los grupos C y D no se consignaron malformaciones. El ácido retinoico administrado intraperitonealmente el dìa 8 p.f en dosis de 40 y 20 mg/kg de peso se comporta como un teratógeno en los embriones de ratón, existiendo además diferencias significativas entre las malformaciones generadas por ambas dosis de ácido retinoico. La primera concentración afecta los huesos de los tres segmentos estudiados (cráneo-cervical, toracoabdominal, y pélvico) y la segunda concentración sólo afecta a dos segmentos (cráneo-cervical y toracoabdominal). Ambos tratamientos afectan los segmentos en una gradiente céfalo caudal, independiente del origen embrionario de las estructuras. Esto se debería a que los cambios en las gradientes de ácido retinoico alteran el comportamiento de células de la cresta neural craneal y el orden de la expresión de genes Hox.

The deficit and excess of vitamin A causes birth defects affecting different organ systems. The objectives of this study are to determine the effect caused by the administration of different doses of retinoic acid on bone morphogenesis of the axial skeleton in embryonic mouse Mus musculus. By simple randomization newly pregnant females were distributed into 4 categories: A, B, C and D. On day 8 post fertilization, 40 mg/kg was administered by weight of retinoic acid to the group A, 20 mg/kg body weight of the group B solution 1 ml/kg body weight of dimethyl sulfoxide and group C. Group D is the control group. On day 17 of gestation the females and their fetuses were anesthetized and euthanized with an overdose of intraperitoneal sodium pentothal. Fetuses from each litter were processed using diaphanization and Alcian blue staining to hyaline cartilage and alizarin to observe bone tissue. The results are expressed as percentages of malformations in the following three segments: 1) cranio-cervical spine, 2) thoracic and abdominal segment and 3) pelvic segment, considering 100% when all the bony elements were compromised. Fisher's exact test for comparison of frequencies of malformations was used and considered statistically significant when p<0.05. In group A, major malformations and defects were evident in the indemnity of the cranial vault, exencephaly, defects in the number of vertebrae, and fusion of ribs. In group B minor malformations as numerical alterations and rib fusions were observed. Significant differences were found between both groups. In groups C and D no malformations were recorded. Retinoic acid administered intraperitoneally at doses of 40 and 20 mg/kg acts as a teratogen in mouse embryos. There are significant differences between the defects induced by concentrations of 40 mg/k and 20 mg/k of retinoic acid. Both concentrations affect the bones of the three segments studied (cranio cervical, thoraco-abdominal and pelvic) in a cephalo caudal gradient, independent of the embryonic origin of the structures. Changes in retinoic acid concentration alter the behavior of cranial neural crest and changing the order of the HOX gene expression in the axial skeleton.

Leucemia promielocítica aguda: Resultados del protocolo terapéutico LPA2000, Programa Nacional de Cáncer del Adulto (PANDA), Ministerio de Salud, Chile / Acute promyelocytic leukemia: Results of the Chilean protocol LPA2000

Background: The current recommendations for treatment of patients with newly diagnosed acute promyelocytic leukemia (APL) include all-trans-retinoic acid (ATRA) and anthracycline based chemotherapy. Aim: To evaluate the results of the Chilean protocol following the LPA99 regimen of the Spanish PETHEMA group, except for the replacement of Idarubicin by Daunorubicin. Patients and Methods: Induction consisted of Daunorubicin 45 mg/m² on days 2, 4, 6 and 8 plus ATRA 45 mg/m² daily until complete remission. Patients in complete remission (CR) received three monthly chemotherapy courses: Daunorubicin 45 mg/m²/d/4days i.v. and ATRA 45 mg/m²/d/15 days p.o. (course no. 1); Mitoxantrone 10 mg/m²/d/5 days i.v. and ATRA 45 mg/m²/d/15 days p.o. (course no. 2); Daunorubicin 60 mg/m²/d/ day 1 i.v. in the low risk group, and 1 and 2 in the intermediate-high risk groups and ATRA 45 mg/m²/d/15 days p.o. (course no. 3). Maintenance therapy consisted of mercaptopurine 90 mg/m²/d p.o., methotrexate 15 mg/m²/wk p.o. and, ATRA intermittently, 45 mg/m²/d p.o. for 15 days every three months. Results: Between January 2000 and December 2005, 56 patients with newly diagnosed APL from 10 centers were enrolled. A total of 46 patients achieved CR (85%), 8 (15%) died of early complications, seven patients relapsed, with a 16% relapse risk at three years. The 5-year Kaplan-Meier estimates of overall survival and relapse-free survival were 64% and 84% respectively. Conclusions: These data indicate that this protocol has a good antileukemic effect but further reduction of early death and relapse, especially in the high risk group is needed.

Embriopatia do ácido retinóico: relato de dois casos associados ao uso da isotretinoína / Retinoic acid embryopathy: report of two cases associated with the use of isotretinoin

Os autores apresentam dois casos associados ao uso da isotretinoína antes ou durante o período gestacional, com seus aspectos característicos e variações, sendo uma criança do sexo feminino e outra do sexo masculino. Descritos para divulgação no meio médico das possíveis complicações do uso da isotretinoína nas mulheres em idade fértil levando em conta a gravidade das malformações nos diferentes sistemas do corpo humano.

effect of intracerebroventricular microinjection of retinoic acid on pain threshold of male rats

Pain is an unpleasant feeling which humans experience. It is a warning sign of the damaged tissue. Due to the awful sense of pain, scientists always attempt to relieve it. Retinoic acid [RT], an active metabolite of natural vitamin A has important roles in modulation of the inflammatory responses. The aim of the present study was to analyze the pain threshold of rats which had microinjections of RT, applying acute and chronic models. In this study, the tail flick and formalin tests were used to determine pain threshold. In each test, the acute and chronic pain thresholds of 252 Wistar male rats [275 +/- 25 gr] were assayed. The druge were injected in the acute model one-dose 30 minutes before behavioral testing and in chronic model two-dose for one or two-weeks. The rats of both models divided randomly into six groups [n = 7]. In four treatment groups retinoic acid [RT] intra cerebro ventricular [i.C.V] were injected as dosage of 0.5, 3 and 6 [micro g/kg] micrograms per kilogram. In control group, was microinjected by ACSF. In vehicle group injected RT solvent [DMSO+ Distil water]. The resuits Showed acute injection of RT did not change pain thresholds in the tail-flick methd, but the chronic administration of RT [0.5, 1, 3, 6 micro g/kg] reduced tail-flick latencies of the rats [p < 0.05] in compare to DMSO group. The threshold of pain in the first phase of formalin test was reduced after injection of 3 micro g/kg of RT for two weeks. It was concluded that chronic i.c.v. injections of RT can induce significant hyperalgesia in rat

Promotive Effect of Minoxidil Combined with All-trans Retinoic Acid (tretinoin) on Human Hair Growth in Vitro

Minoxidil induces hair growth in male pattern baldness and prolongs the anagen phase. All-trans retinoic acid (ATRA) has been reported to act synergistically with minoxidil in vivo: they can enhance more dense hair regrowth than either compound alone. We evaluated the effect of minoxidil combined with ATRA on hair growth in vitro. The effect of co-treatment of minoxidil and ATRA on hair growth was studied in hair follicle organ culture. In cultured human dermal papilla cells (DPCs) and normal human epidermal keratinocytes, the expressions of Erk, Akt, Bcl-2, Bax, P53 and P21 were evaluated by immunoblot analysis. Minoxidil plus ATRA additively promoted hair growth in vitro, compared with minoxidil alone. In addition, minoxidil plus ATRA elevated phosphorylated Erk, phosphorylated Akt and the ratio of Bcl-2/Bax, but decreased the expressions of P53 and P21 more effectively than by minoxidil alone. Our results suggest that minoxidil plus ATRA would additively enhance hair growth by mediating dual functions: 1) the prolongation of cell survival by activating the Erk and Akt signaling pathways, and 2) the prevention of apoptosis of DPCs and epithelial cells by increasing the ratio of Bcl-2/Bax and downregulating the expressions of P53 and P21.

Combinational Treatment with Retinoic Acid Derivatives in Non-small Cell Lung Carcinoma In Vitro

The growth inhibitory effects of four retinoic acid (RA) derivatives, 9-cis RA, 13-cis RA, N-(4-hydroxyphenyl) retinamide (4-HPR), and all-trans retinoic acid (ATRA) were compared. In addition, the effects of various combinations of these four agents were examined on non-small cell lung carcinoma (NSCLC) cell-lines, and on the expressions of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) on these cells. At the clinically achievable concentration of 1 micrometer, only 4-HPR inhibited the growths of H1299 and H460 cells-lines. However, retinoic acid receptor beta(RAR beta) expression was up-regulated on H460 and H1299 cells treated with 1 micrometer of ATRA, 13-cis RA, or 9-cis RA. All NSCLC cell lines showed growth inhibition when exposed sequentially to 1 micrometer ATRA and 0.1 micrometer 4-HPR. In particular, sequential treatment with 1 micrometer ATRA or 13-cis RA and 4-HPR markedly inhibited H1703 cell growth; these cells exhibited no basal RAR beta expression and were refractory to 4-HPR. However, in NSCLC cell lines that expressed RAR beta, the expressional levels of RAR beta were up-regulated by ATRA alone and by sequential treatment with ATRA and 4-HPR. 4-HPR was found to be the most active of the four agents in terms of NSCLC growth-inhibition. Moreover, sequential treatments with ATRA or 13-cis RA followed by 4-HPR were found to have synergistic growth-inhibitory effects and to regulate RAR expression.

Is interferon-alpha and retinoic acid combination along with radiation superior to chemo-radiation in the treatment of advanced carcinoma of cervix?

Locally advanced cervical cancers comprise a large majority of the gynecologic cancers in India and other developing countries. Concurrent chemo-radiation has improved the survival of high risk stage I and stage II cervical cancers. There is no evidence that the same survival benefit has been achieved with chemo-radiation in stage III and stage IV disease. Interferon-alpha and Retinoic acid have synergistic anti-proliferative activity. In combination with radiation, they substantially enhance the sensitivity of the squamous carcinoma cells to radiation. Based on these observations from the in vitro studies, a few clinical trials have evaluated the combination of interferon-alpha and Retinoic acid, concomitant with radiation, to treat cervical cancers. The results from these early trials were encouraging and the combination had minimal toxicities. However, till date, no phase III randomized controlled trial has been done to evaluate this therapeutic modality.

Pharmaceutical and clinical study of tretinoin from different dermatological formulations

Tretinoin can be used in the treatment of a variety of skin diseases, depending on its concentration. Formulations containing 0.05% tretinoin have been used in acne vulgaris. An important objective of this study was to show the fact that using hydrophilic gels [formula I] or emollient cream [formula II] as topical formulation containing 0.05% tretinoin improves clinical efficacy while potentially reducing local irritation traditionally associated with the commercially available topical tretinoin product [formula III]. The gel samples studied were formulations of 0.05% tretinoin in carbopol 940 [a synthetic polymer, formula Ia], sodium carboxymethylcellulose [a semisynthetic polymer, formula Ib], and carbogum [a natural polymer, formula Ic]. Emollient cream is a mixture of polyoxyethylene [2] stearyl ether as surfactant, cetostearyl alcohol as cosurfactant, liquid paraffin and white petrolatum as an oil phase. The aqueous phase contains preservative and 60% water. Evaluations of the suggested formulae were performed through stability studies, rheological measurements, pH determination and tretinoin assay spectrophotometrically. In-vitro permeation study was also done in hydroalcoholic solution [50:50] using Nephrophan dialysis membrane. The gel preparation with the highest diffusion rate was submitted to clinical investigation in comparison to the prepared cream as well as the commercial one. Such clinical attempt was made on 18 patients with mild to moderate acne for a period of 12 weeks regarding the clinical efficacy and the degree of reducing adverse effects. The formulations studied showed both good chemical and physical stabilities when submitted to rheological determinations, pH measurements and drug assay through out a 6-mounth period. The hydrophilic gel formulations as well as the emollient cream exhibited better release profiles if compared with the commercial cream. This fact is reflected on the clinical results as both the gel and emollient cream significantly improved therapeutic response at all evaluation time intervals together with much less erythema and burning if compared to the commercial one. But the gel form gave the most distinct results

Increased smooth muscle actin expression from bone marrow stromal cells under retinoic acid treatment: an attempt for autologous blood vessel tissue engineering.

Vascular replacement in vital organs is sometimes necessary for human life for example because of atherosclerosis. Blood vessel tissue engineering is applied for autologous transplantations to avoid graft rejections. Stem cells are used for blood vessel tissue engineering because they are the origin of smooth muscle cells, endothelial cells and fibroblasts. This paper shows that bone marrow stromal cells (BMSCs) can be induced to differentiate into the early stage of smooth muscle cells by using 0.01 microM retinoic acid. The differentiation of BMSCs to smooth muscle cells was detected by the expression of smooth muscle alpha actin (SM alpha-actin), the earliest smooth muscle cell marker. The SM alpha-actin marker expression was demonstrated using indirect immunofluorescence technique and Western blot analysis. The induction of BMSC to form early stages of smooth muscle cells in this study is appropriate for blood vessel tissue engineering because the early stage smooth muscle cells may be stimulated to develop vascular walls with endothelial cells using a co-culture system.

Induction of type I collagen and osteocalcin in human dental pulp cells by retinoic acid.

Retinoic acid has been known to play a key role in the regulation of bone cell differentiation and function. The effects of retinoic acid on human dental pulp cells, which contain several characteristics similar to those of bone cells, has yet to be elucidated extensively. The effects of retinoic acid on human dental pulp cells in terms of type I collagen and osteocalcin induction were investigated in vitro. Dental pulp cells obtained from the teeth of young patients (age between 18-22 years) were cultured and subsequently treated with various concentrations of retinoic acid (0, 10(-7), 10(-6), 10(-5) M) in serum-free DMEM. At different time intervals (8, 12 and 24 hours), the levels of type I collagen and osteocalcin secreted were determined using Type I Procollagen C-Peptide and Gla-type Osteocalcin EIA kits, respectively. Induction effects were evaluated using analysis of variance and the Duncan's multiple rank test. Retinoic acid at concentrations of 10(-5), 10(-6), 10(-7) M was able to induce type I collagen and osteocalcin production in human dental pulp cells within 12 hours of exposure. Dose-dependent induction was observed only after 24 hours. A two-fold increase in osteocalcin level was detected after exposed to 10(-5) M retinoic acid within 24 hours. Our data suggest that retinoic acid at concentrations of 10(-5), 10(-6), 10(-7) M has the ability to induce type I collagen and osteocalcin secretions in human dental pulp cells in vitro.

Treatment of acute promyelocytic leukemia: A single institution experience / Tratamiento de la leucemia promielocítica aguda: Experiencia de una sola institución

The results of the treatment of 14 patients with promyelocytic leukemia (PML) treated with all trans-retinoic acid (ATRA), combined chemotherapy (CT) and prophylactic prednisone are reported; the median age was 30 years (range 7 - 49). A complete remission (CR) was obtained in 13 / 14 patients (93%). All patients were given ATRA fully as outpatients; the CR was achieved after the administration of ATRA in five patients, whereas in the remaining eight, CT was required to achieve it. There were no instances of the ATRA syndrome. One patient relapsed with a PML/RAR-a negative PML 575 days after achieving the CR, failed to respond again to ATRA and died. The median overall (OS) and disease free survival (DFS) has not been reached, being above 4,000 days, whereas the 12-month DFS was 93%, the three and five years DFS being 85%. The treatment employed differs from others in: Oral prednisone is used prophylactically, ATRA is given on an outpatient basis and adriamycin is used instead of other anthracyclines. The results are similar to those obtained in other centers worldwide and it is possible that the prophylactic administration of prednisone precluded the development of the full-blown ATRA syndrome in this group of patients.

Se informan los resultados del tratamiento en una sola institución de 14 pacientes con leucemia aguda promielocítica (LAPM) en quienes se empleó la combinación de ácido holotrans-retinoico (ATRA) quimioterapia combinada y prednisona profiláctica. La mediana de edad fue de 30 años (rango 7-49). Se obtuvo remisión completa (hematológica y molecular) (RC) en 13 pacientes (93%); a todos los pacientes se les administró el ATRA de manera ambulatoria. La RC se obtuvo con el ATRA en cinco pacientes; en los demás la RC se obtuvo después de habérseles administrado la quimioterapia con citarabina/adriamicina. No hubo ningún caso de síndrome de ATRA. Un paciente recayó con una LAPM PML/ RAR-a negativa, 575 días después de haber logrado la RC y falleció. Otro paciente recayó 20 meses después de haber logrado la RC y fue rescatado con el mismo esquema de tratamiento; permanece en segunda remisión molecular por más de seis años. La mediana de supervivencia (SV), tanto global como libre de recaídas de todo el grupo, no se ha alcanzado y es mayor de 4,000 días, en tanto que la SV a 12 meses fue de 93% y a tres y cinco años de 85%. El esquema de tratamiento usado difiere de otros en que se usa prednisona oral, se administra el ATRA de manera ambulatoria y se usa adriamicina y no otras antracidinas; los resultados son similares a los obtenidos con otros esquemas parecidos en otros sitios del mundo; es posible que el uso profiláctico de prednisona haya eliminado la ocurrencia del síndrome de ATRA.

[Efficacy of 0.05% topical solution of tretinoin on healing of chronic ulcers and comparison of it with 1% topical cream of phenytoin]

Chronic ulcer with any kind of etiology is one of the therapeutic problems for patients and medical services. With respect to appropriate effects of retinoids on different stages of wound healing, we decided to evaluate efficacy of 0.05% topical solution of tretinoin on topical treatment of ulcers in comparison with 1% topical cream of phenytoin,that its effects on wound healing has been approved in several studies. In an interventional, clinical trial topical effect of these two drugs on healing of chronic ulcers of 30 patients with 37 ulcers was compared, with random allocation patients divided to two groups and finally 15 patients with 18 ulcers treated with l%topical cream of phenytoin and 15 patients with 19 ulcers treated with 0.05% topical solution of tretinoin. Then followed up for 6 weeks and evaluated for criteria of clinical recovery [size, depth, secretion and pain] in weekly visits. Analytic tests were done by using the chi-square test and P<0.05 was accepted as significant. 'At the end of, the treatment in phenytoin group 42.6 +/- 44.9% and in tretinoin group 44.7 +/- 43.4% of ulcers width were reduced. Also at this time ulcers' depth were diminished whereas in phenytoin group 55.6% and in tretinoin group 26.3% of those were in superficial dermis. Before treatment in phenytoin group 55.6% of ulcers were without pain though after it 100% of them had no pain. In tretinoin group ulcers without pain increased from 78.9% before to 84.2% after treatment. Percentage of ulcers with no secretion increased from 33.3% to 55.6% in phenytoin group and from 26.3% to 68.4% in tretinoin group With respect to results, tretinoin solution as phenytoin cream can be used as an appropriate topical treatment for chronic ulcer

All-transretinoic acid and chemotherapy in the treatment of acute promyelocytic leukemia.

BACKGROUND: All-transretinoic acid (ATRA) and chemotherapy has improved complete remission rates and disease free survival in acute promyelocytic leukemia (APL). There is scanty data from Middle East. AIM: To determine the efficacy of ATRA and multi-agent combination chemotherapy in treatment of APL in a single Centre in Kuwait. SET-UPS AND DESIGN: Tertiary cancer centre, retrospective study. METHODS AND MATERIAL: All newly diagnosed APL patients were treated with oral ATRA 45 mg/m2 daily until complete remission (CR), intravenous daunorubicin 50 mg/m2 on days 1,3 and 5, cytosine arabinoside 100 mg/m2 12 hrly on days 1 through 10 and etoposide 100 mg/m2 on days 1 through 5. Post remission three courses of intensive consolidation chemotherapy were administered. Since October 1999, maintenance chemotherapy consisting of oral 6 mercaptopurine 9 mg/m2 daily, methotrexate 15 mg/m2 weekly and ATRA 45 mg/m2 for 2 weeks every three months was added. Complete remission rates and duration, relapse rate and toxicity were studied. RESULTS: 22 of 24 evaluable patients (91.6%) achieved CR. The median duration of remission was 13 months (range 2-55 months). Three patients (12.5%) relapsed. Two patients (8.3%) developed retinoic acid syndrome and responded to dexamethasone. Five patients (20.8%) died one each of refractory disease, during remission induction and of relapse. Two patients died while in remission. CONCLUSION: ATRA and combination chemotherapy results in high complete remission rates and low relapse rate in newly diagnosed APL. Maintenance therapy may be useful in preventing relapses.

A importância do ácido trans-retinóico no tratamento da leucemia promielocítica aguda e suas complicaçöes / The importance of trans-retinoic acid in the acute promyelocytic leukemia treatment and its complications

Os autores apresentam uma revisao da literatura relacionada à utilizaçäo do ácido trans-retinóico na Leucemia Mielóide Aguda M3. Apresentam ainda os principais parâmetros para a sua utilizaçäo, bem como os cuidados no reconhecimento e tratamento da síndrome do Acido all-transretinóico. Os autores ilustram tal revisäo com um caso em que ocorreram as mais importantes complicaçöes com a utilizaçao do Acido all-transretinóico. Os modificadores da resposta biológica têm sido cada vez mais usados no tratamento de neoplasias, e a utilizaçäo do Acido all-transretinóico tem sido altamente significativa no tipo de LMA-M3.

Enfermedad de Darier familiar / Familial Darier's disease

La enfermedad de Darier familiar es un desorden genético de la queratinización, con forma de transmisión autosómica dominante, infrecuente, caracterizada por presentar pápulas hiperqueratósicas en zonas seborreicas. Presentamos 2 pacientes, madre e hijo, que presentaron hallazgos clínicos e histopatológicos típicos de la enfermedad de Darier, con afectación de mucosas, cuero cabelludo y uñas. Se indicó tratamiento tópico con tretinoína 0,05 por ciento y lactato de amonio al 12 por ciento con buena respuesta estética. El motivo de esta publicación está dado por la infrecuencia de esta enfermedad en forma familiar y la buena respuesta estética a la terapéutica local instituida