Epidemiology of Melanoma in Spain: Estimation of Number of Patients With Stage III Disease Eligible for Adjuvant Therapies. / Epidemiología del melanoma en España: estimación de los pacientes con melanoma con estadio III candidatos al tratamiento adyuvante.

BACKGROUND AND OBJECTIVE: Accurate information on the incidence of melanoma by stage and a better understanding of transition between stages are important for determining the burden of disease and assessing the impact of new adjuvant therapies on recurrence and survival. The aim of this study was to estimate the incidence rates of the various stages of melanoma in Spain and to estimate the number of patients with stage III disease who are eligible for adjuvant systemic therapies. MATERIALS AND METHOD: We built an epidemiological model using prospectively collected data from patients diagnosed with de novo or recurrent melanoma between 2012 and 2016 in the melanoma units of 4 public hospitals. RESULTS: The estimated crude incidence rates for stage I and II melanoma were 7 and 2.9 cases per 100,000 person-years, respectively. The corresponding rates for stage III and IV melanoma were 1.9 and 1.3 cases per 100,000 person-years; 25.8% of patients with stage III melanoma were stage IIIA, 47% were stage IIIB, and 27.3% were stage IIIC. The respective estimated incidence rates for recurrent stage III and IV melanoma were 1.1 and 0.9 cases per 100,000 person-years. Overall, 54% of patients with recurrent stage III melanoma had progressed from stage I or II; the other cases corresponded to changes in substage. Of the patients with stage III melanoma, 85% of those with a de novo diagnosis and 80% of those who had relapsed had resectable disease, meaning they were eligible for adjuvant therapy; 47% of these patients had a BRAF mutation. CONCLUSIONS: The above estimates could have a major impact on health care resource planning. Assessing the number of patients with melanoma who are eligible for adjuvant therapies in melanoma could help decision-makers and clinicians anticipate future needs for the management of this disease.

Psychosocial repercussion of migraine: is it a stigmatized disease?

INTRODUCTION: Stigma manifests both in prejudices and rejection from society towards patients who suffer from a specific pathology, and by patient's internalization of this discrimination, with the consequent repercussions on their state of mind and quality of life. The aim of the study was to quantify the stigma associated with migraine and analyze whether it is related to the clinical-demographic characteristics of the patients, as well as the possible impact on their daily lives. MATERIALS AND METHODS: The stigma scale for chronic illness (SSCI) and other questionnaires were administered to 56 patients with episodic migraine (EM), 18 with chronic migraine (CM), and 21 with epilepsy, as a control group. RESULTS: The mean SSCI score was higher (51.6 ± 15.0) in the CM group than in the EM (45.0 ± 13.5) and epilepsy (47.6 ± 15.5) groups, without reaching statistical significance. In addition, the score was higher in patients who were unemployed, divorced, and in those who had migraine with aura. A statistically significant correlation was found between the SSCI score and the impact of migraine on daily life, the presence of stress, anxiety and depression, and low self-esteem. CONCLUSIONS: There is a stigma around migraine in our society, which seems to be more prevalent in patients with certain socio-demographic characteristics, and that is related to stress, mood alterations, and low self-esteem. Trying to reduce stigma could contribute to improve the control of migraine and reduce the impact of the disease at a socio-economic level.

Mitogen-activated protein kinase phosphatase-1 (MKP-1) impairs the response to anti-epidermal growth factor receptor (EGFR) antibody cetuximab in metastatic colorectal cancer patients.

BACKGROUND: The validation of KRAS mutations as a negative marker of response to anti-epidermal growth factor receptor (EGFR) antibodies has meant a seminal advance towards treatment individualisation of colorectal cancer (CRC) patients. However, as a KRAS wild-type status does not guarantee a response to anti-EGFR antibodies, a current challenge is the identification of other biomarkers of response. On the basis of pre-clinical evidence, we hypothesised that mitogen-activated protein kinase phosphatase-1 (MKP-1), a phosphatase that inactivates MAPKs, could be a mediator of resistance to anti-EGFR antibodies. METHODS: Tumour specimens from 48 metastatic CRC patients treated with cetuximab-based chemotherapy were evaluated for KRAS and BRAF mutational status and MKP-1 expression as assessed by immunohistochemistry. RESULTS: As expected, clinical benefit was confined to wild-type KRAS and BRAF patients. Mitogen-activated protein kinase phosphatase-1 was overexpressed in 16 patients (33%) and was not associated with patient baseline clinicopathological characteristics and KRAS mutational status. All patients with BRAF mutations (n=3) had MKP-1 overexpression. Among KRAS wild-type patients, MKP-1 overexpressors had a 7% response rate (RR), whereas patients not overexpressing MKP-1 had a 44% RR (P=0.03). Moreover, median time to progression was significantly longer in MKP-1 non-overexpressing patients (32 vs 13 weeks, P=0.009). CONCLUSION: These results support the concept of MKP-1 as a promising negative marker of response to cetuximab-based treatment in CRC patients with wild-type KRAS.

Trichinella: differential expression of angiogenic factors in macrophages stimulated with antigens from encapsulated and non-encapsulated species.

The newborn larval stage of Trichinella spiralis enters the host striated skeletal muscle cell resulting in the formation of the nurse cell. Vascular Endothelial Growth Factor (VEGF) was detected in cells in the area immediately surrounding the nurse cells. However, no data are available on the antigens involved, the role of other angiogenic factors or the relationship of angiogenesis with Nitric Oxide (NO) production. Using macrophage cell culture we study the effect of different Trichinella L1 antigens from one encapsulated (T. spiralis) and one non-encapsulated (Trichinellapseudospiralis) on the expression of VEGF and basic Fibroblast Growth Factor (FGF2). Also, we investigate the relationship between the production of NO and angiogenic mediators. The results show that encapsulated and non-encapsulated Trichinella species are different in their capacity to stimulate the expression of VEGF and FGF2 from host macrophages. Finally, there is no relationship between angiogenic factors and NO production by T. spiralis antigen.

Trichinellosis survey in the wild boar from the Toledo mountains in south-western Spain (2007-2008): molecular characterization of Trichinella isolates by ISSR-PCR.

In Spain, trichinellosis represents a public health problem, with an average of five outbreaks per year, wild boar meat being the main source of infection. A trichinellosis survey (2007-2008 hunting campaign) was carried out on wild boars in the Toledo Mountains (south-western Spain, EU) in the context of a surveillance programme on wildlife diseases. A total of 2216 wild boars from different locations of the region were examined. The examination was carried out by veterinarians in the local abattoir (Matadero Municipal de Toledo). The positive samples were sent to the Department of Parasitology (Facultad de Farmacia, UCM) for experimental isolation and specific identification by inter-simple sequence repeat-polymerase chain reaction (ISSR-PCR). Using this technique we identified 17 isolates as Trichinella spiralis with an electrophoretic profile indistinguishable from the T. spiralis reference strain (ISS48). We confirmed that ISSR-PCR is a robust technique for the molecular identification of Trichinella isolates. According to our results, the prevalence of T. spiralis in wild boars from the Toledo Mountains (>800 m above sea level) during the hunting season was approximately 0.77%. The prevalence of T. spiralis (100% of our observations) is a good example of the persistence of this species in sylvatic conditions (coming from the domestic cycle), if a good wild host is abundant. Our observations confirm the major prevalence of T. spiralis over T. britovi in this region, as well as the risk to human health represented by the consumption of uninspected wild boar meat.

Serum HER2 extracellular domain predicts an aggressive clinical outcome and biological PSA response in hormone-independent prostate cancer patients treated with docetaxel.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpression has been linked to hormone-independent prostate cancer (HIPC) progression. Its clinical value and correlation with therapy is not defined. PATIENTS AND METHODS: Patients with HIPC treated with docetaxel (Taxotere) were prospectively tested for serum HER2 extracellular domain (ECD) by immunoanalysis. HER2 was determined by immunohistochemistry and fluorescence in situ hybridization (FISH) in tumor samples. RESULTS: Sixty-nine patients were included. Twenty-four (34.8%) patients had high HER2 ECD (>15 ng/ml). Prostate-specific antigen (PSA) response was 58% for patients with low HER2 ECD and 36% for patients with high HER2 ECD (P = 0.046). HER2 ECD levels were an independent prognostic factor for time to PSA progression [hazard ratio (HR) 2.82; 95% confidence interval (CI) 1.22-6.50; P = 0.015] and overall survival (HR 3.24; 95% CI 1.38-7.59; P = 0.007). Tissue samples from 17 patients were tested for HER2. Patients with negative HER2 tissue expression had lower HER2 ECD levels (median 10.5 +/- 2.7 versus 30.5 +/- 24.8 ng/ml; P = 0.016). FISH was negative in all samples. CONCLUSIONS: High HER2 ECD levels in serum are associated with a worst clinical outcome of HIPC patients treated with docetaxel.

The addition of a new immunomodulator with the adjuvant adaptation ADAD system using fatty acid binding proteins increases the protection against Fasciola hepatica.

Fatty acid binding proteins (FABP) have shown protective immune response against Fasciola hepatica infection. We evaluated the protection induced by the Fh12 FABP from F. hepatica (Fh12) combined with the new immunomodulator the lipidic aminoalcohol OA0012 in the ADAD system in mice and sheep. In this work we introduced a lipidic aminoalcohol OA0012 as immunomodulator alone or in combination with the hydroalcoholic extract of Phlebodium pseudoaureum; PAL. Mice vaccinated with ADAD containing OA0012+Fh12 or OA0012+Qs+Fh12 had survival rates of 40-50%. Sheep ADAD-vaccinated with OA0012+Qs+Fh12 showed lower fluke recovery, less hepatic lesions and higher post-infection daily weight gain than F. hepatica infected control animals. Sheep ADAD-vaccinated with OA0012 combined PAL and Qs+Fh12 showed lower fluke recovery (42%), lower adult worms count (57%) lower faecal egg count (38%), less hepatic lesions and higher post-infection daily weight gain than F. hepatica infected control animals. Thus, the addition of a new immunomodulator of synthesis to ADAD system with FABPs increased the protection against F. hepatica.

Pharmacological immunomodulation of surgical trauma.

Surgery and accidental trauma induce changes in the immune response, showing a predominant pattern of activation through the Th2 cell pathway to the detriment of Th1 cell pathway activation. Anapsos is a hydrosoluble extract obtained from Polypodium leucotomos. Anapsos has shown immunomodulating effects in vitro. On a rat experimental model (tibia and fibula fracture), cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, and IL-12) (enzyme-linked immunosorbent assay, ELISA) and cell percentages of CD4, CD8 CD25, CD122, and CD132 (monoclonal antibodies, MoAb) were determined in peripheral blood 7 days before surgery (PRE), 1 day after surgery (1PO), and 7 days after surgery (7PO). On postoperative day 1, rats undergoing fracture show an increase of CD8 percent expression and IL-6 and IL-10 levels, in contrast to rats undergoing fracture plus anapsos treatment. On postoperative day 7, rats undergoing fracture show an increase of IL-6 levels, whereas rats undergoing fracture plus anapsos do not. The IL-12 level decreases on postoperative day 7 in the group with fracture but not in the fracture plus anapsos group. Thus, we conclude that anapsos is able to modulate the immune response after trauma, inhibiting Th2 pathway activation with no effect on Th1 pathway activation. In trauma, Anapsos could prevent the shifting Th1/Th2 balance.

Progress in the development of Fasciola hepatica vaccine using recombinant fatty acid binding protein with the adjuvant adaptation system ADAD.

Fatty acid binding proteins (FABP) have been designed as a potential vaccine against fasciolosis. In this work, the immunoprophylaxis of the recombinant Fh15 FABP from F. hepatica (Fh15) in adjuvant/immunomodulator ADAD system was evaluated using mice and sheep challenged with F. hepatica. The ADAD system combines the Fh15 antigen with an immunomodulator (hydroalcoholic extract of Polypodium leucotomos; PAL) and/or an adjuvant (saponins of Quillaja saponaria; Qs) in a water/oil emulsion (30/70) with a non-mineral oil (Montanide). All the infected control mice died by 41-48 days post-infection. The mice vaccinated with ADAD only with PAL+Fh15 present a survival rate of 40-50% and those vaccinated with ADAD containing PAL+Qs+Fh15 had a survival rate of 50-62.5%. IgG1 antibodies were lower in surviving mice in comparison with non-surviving mice. The sheep vaccinated with ADAD PAL+Qs+Fh15 showed lower fluke recovery (43%), less hepatic lesions and higher post-infection daily weight gain than F. hepatica infected control animals. Thus, the ADAD system using recombinant fatty acid binding proteins from F. hepatica could be a good option to develop vaccines against F. hepatica.

Genetic and immunological characterization of the 14-3-3xi molecule from Schistosoma bovis.

Currently available candidate vaccines against schistosomiasis elicit only partial protection. In addition, the type of immune response that could lead to the highest level of protection against schistosomes has not yet been described. Thus, efforts should be made in both the identification of novel proteins essential for the parasite cycle and in the modulation of immune responses against these novel candidates through the combined use of immunomodulatory molecules. Several parasites have 14-3-3 proteins, and these proteins are known to play a key role in parasite biology. In the present work, we report the isolation and characterization of a new 14-3-3 gene from Schistosoma bovis and offer new information regarding the genetic structure of the gene. In addition, we have produced the corresponding recombinant protein. Finally, we describe the immune responses elicited by this protein when combined with 4 different immunomodulators in immunized mice.

Epidemiología del melanoma en España: estimación de los pacientes con melanoma con estadio III candidatos al tratamiento adyuvante / Epidemiology of Melanoma in Spain: Estimation of Number of Patients With Stage III Disease Eligible for Adjuvant Therapies

Antecedentes y objetivo: Para estimar la carga real del melanoma y el impacto de las nuevas terapias adyuvantes sobre las recaídas y la supervivencia, se precisa conocer con mayor exactitud la incidencia por estadios y analizar la transición entre ellos. Este estudio pretende estimar dicha incidencia y determinar el número de pacientes en estadio III que podrían beneficiarse del tratamiento sistémico adyuvante en España. Materiales y método: Se elaboró un modelo epidemiológico basado en datos de pacientes diagnosticados de melanoma o en recaída, recogidos prospectivamente durante 2012-2016 por cuatro unidades de melanoma de centros sanitarios públicos. Resultados: Las tasas brutas de incidencia estimadas para estadios I y II se situaron en 7 y 2,9 casos por 100.000 personas-año, respectivamente. Para estadio III se estimó en 1,9 (25,8% en IIIA, 47% en IIIB, y 27,3% en IIIC), siendo la de estadio IV de 1,3. La tasa de recaídas en estadio III se estimó en 1,1, siendo para estadio IV de 0,9. El 54% de recaídas a estadio III procedían de estadios I/II, mientras que el resto progresaban desde subestadios III. En estadio III, un 85% de nuevos diagnósticos y un 80% de recaídas fueron resecables, por tanto, candidatos a adyuvancia, de los cuales el 47% presentaba mutación en BRAF. Conclusiones: Estas estimaciones podrían tener un impacto importante en la planificación de los recursos sanitarios. La proyección en el número de potenciales candidatos a adyuvancia puede ayudar a decisores y clínicos a anticiparse a futuras necesidades en el manejo del melanoma (AU)

Background and objective: Accurate information on the incidence of melanoma by stage and a better understanding of transition between stages are important for determining the burden of disease and assessing the impact of new adjuvant therapies on recurrence and survival. The aim of this study was to estimate the incidence rates of the various stages of melanoma in Spain and to estimate the number of patients with stage III disease who are eligible for adjuvant systemic therapies. materials and method: We built an epidemiological model using prospectively collected data from patients diagnosed with de novo or recurrent melanoma between 2012 and 2016 in the melanoma units of 4 public hospitals. Results: The estimated crude incidence rates for stage I and II melanoma were 7 and 2.9 cases per 100,000 person-years, respectively. The corresponding rates for stage III and IV melanoma were 1.9 and 1.3 cases per 100,000 person-years; 25.8% of patients with stage III melanoma were stage IIIA, 47% were stage IIIB, and 27.3% were stage IIIC. The respective estimated incidence rates for recurrent stage III and IV melanoma were 1.1 and 0.9 cases per 100,000 person-years. Overall, 54% of patients with recurrent stage III melanoma had progressed from stage I or II; the other cases corresponded to changes in substage. Of the patients with stage III melanoma, 85% of those with a de novo diagnosis and 80% of those who had relapsed had resectable disease, meaning they were eligible for adjuvant therapy; 47% of these patients had a BRAF mutation. Conclusions: The above estimates could have a major impact on health care resource planning. Assessing the number of patients with melanoma who are eligible for adjuvant therapies in melanoma could help decision-makers and clinicians anticipate future needs for the management of this disease (AU)

[Translated article] Epidemiology of Melanoma in Spain: Estimation of Number of Patients With Stage III Disease Eligible for Adjuvant Therapies / Epidemiología del melanoma en España: estimación de los pacientes con melanoma con estadio III candidatos al tratamiento adyuvante

Background and objective: Accurate information on the incidence of melanoma by stage and a better understanding of transition between stages are important for determining the burden of disease and assessing the impact of new adjuvant therapies on recurrence and survival. The aim of this study was to estimate the incidence rates of the various stages of melanoma in Spain and to estimate the number of patients with stage III disease who are eligible for adjuvant systemic therapies. materials and method: We built an epidemiological model using prospectively collected data from patients diagnosed with de novo or recurrent melanoma between 2012 and 2016 in the melanoma units of 4 public hospitals. Results: The estimated crude incidence rates for stage I and II melanoma were 7 and 2.9 cases per 100,000 person-years, respectively. The corresponding rates for stage III and IV melanoma were 1.9 and 1.3 cases per 100,000 person-years; 25.8% of patients with stage III melanoma were stage IIIA, 47% were stage IIIB, and 27.3% were stage IIIC. The respective estimated incidence rates for recurrent stage III and IV melanoma were 1.1 and 0.9 cases per 100,000 person-years. Overall, 54% of patients with recurrent stage III melanoma had progressed from stage I or II; the other cases corresponded to changes in substage. Of the patients with stage III melanoma, 85% of those with a de novo diagnosis and 80% of those who had relapsed had resectable disease, meaning they were eligible for adjuvant therapy; 47% of these patients had a BRAF mutation. Conclusions: The above estimates could have a major impact on health care resource planning. Assessing the number of patients with melanoma who are eligible for adjuvant therapies in melanoma could help decision-makers and clinicians anticipate future needs for the management of this disease (AU)

Antecedentes y objetivo: Para estimar la carga real del melanoma y el impacto de las nuevas terapias adyuvantes sobre las recaídas y la supervivencia, se precisa conocer con mayor exactitud la incidencia por estadios y analizar la transición entre ellos. Este estudio pretende estimar dicha incidencia y determinar el número de pacientes en estadio III que podrían beneficiarse del tratamiento sistémico adyuvante en España. Materiales y método: Se elaboró un modelo epidemiológico basado en datos de pacientes diagnosticados de melanoma o en recaída, recogidos prospectivamente durante 2012-2016 por cuatro unidades de melanoma de centros sanitarios públicos. Resultados: Las tasas brutas de incidencia estimadas para estadios I y II se situaron en 7 y 2,9 casos por 100.000 personas-año, respectivamente. Para estadio III se estimó en 1,9 (25,8% en IIIA, 47% en IIIB, y 27,3% en IIIC), siendo la de estadio IV de 1,3. La tasa de recaídas en estadio III se estimó en 1,1, siendo para estadio IV de 0,9. El 54% de recaídas a estadio III procedían de estadios I/II, mientras que el resto progresaban desde subestadios III. En estadio III, un 85% de nuevos diagnósticos y un 80% de recaídas fueron resecables, por tanto, candidatos a adyuvancia, de los cuales el 47% presentaba mutación en BRAF. Conclusiones: Estas estimaciones podrían tener un impacto importante en la planificación de los recursos sanitarios. La proyección en el número de potenciales candidatos a adyuvancia puede ayudar a decisores y clínicos a anticiparse a futuras necesidades en el manejo del melanoma (AU)

5-Year management and outcomes of penetrating neck injury in a trauma center. Penetrating neck injury / Manejo y resultados de trauma penetrante de cuello en 5 años dentro de un centro de urgencias. Trauma penetrante de cuello

Background Penetrating neck injuries represent 5–10% of all traumatic injuries, these bring with them a high rate of morbidity and mortality due to vital structures that could be injured in this area. The aim of this study was to determine the epidemiological and clinical characteristics of penetrating neck injuries. Methods This was a retrospective, unicentric and descriptive study that included all patients who underwent neck exploration surgery. Results A total of 70 neck exploration cases were reviewed, 34 (49%) didn’t had any injury. Thirty (43%) had at least one hard sign, 42 (60%) patients showed at least one soft sign. Statistical analysis showed only surgical time (252±199.5 vs. 155±76.4; p=0.020) and transfusions (1.87±3 vs. 0.4±0.856; p=0.013) were statistically significant. We report a mortality of 2 (3%) patients. Conclusions Our prevalence of neck surgical exploration without vascular injury was slightly higher (49% vs. 40%) than literature. We highlight the importance of not performing neck explorations in all patients who present a penetrating injury. We did not obtain differences between groups for hard signs and soft signs. We were not able to identify whether or not there would be an injury based on clinical characteristics. Imaging studies should be performed to avoid unnecessary neck explorations; however, depending on the clinical scenario some surgery cannot be avoided (AU)

Antecedentes Las lesiones penetrantes de cuello representan entre el 5-10% de todas las lesiones traumáticas, estas traen consigo una alta tasa de morbimortalidad por estructuras vitales que podrían lesionarse en esta área. El propósito de este estudio fue determinar las características epidemiológicas y clínicas del trauma penetrante de cuello. Métodos Estudio retrospectivo, unicéntrico y descriptivo que incluyó a todos los pacientes sometidos a cirugía de exploración de cuello. Resultados Se revisaron un total de 70 casos de exploración de cuello, 34 pacientes (49%) no presentaron ninguna lesión. Treinta pacientes (43%) tenían al menos un signo duro, 42 pacientes (60%) mostraron al menos un signo blando. El análisis estadístico mostró que solo el tiempo quirúrgico (252±199,5 vs. 155±76,4; p=0,020) y las transfusiones (1,87±3 vs, 0,4±0,856; p=0,013) fueron estadísticamente significativas. Reportamos la mortalidad de 2 pacientes (3%). Conclusiones Nuestra prevalencia de exploración quirúrgica de cuello sin lesión vascular fue ligeramente superior (49 vs. 40%) que la literatura. Destacamos la importancia de no realizar exploraciones de cuello en todos los pacientes que presentan una lesión penetrante. No obtuvimos diferencias entre grupos para signos duros y signos blandos. No pudimos identificar si hubiera o no una lesión en función de las características clínicas. Se deben realizar estudios de imagen para evitar exploraciones innecesarias del cuello; sin embargo, dependiendo del escenario clínico, no se pueden evitar algunas cirugías (AU)

Molecular characterization of Trichinella genotypes by inter-simple sequence repeat polymerase chain reaction (ISSR-PCR).

A bulk analysis of inter-simple sequence repeat-polymerase chain reaction (ISSR-PCR) provides a quick, reliable, and highly informative system for DNA banding patterns that permit species identification. The present study evaluates the applicability of this system to Trichinella species identification. After a single amplification carried out on a single larva with the primer 816([CA]nRY) under high stringency conditions, which provide high reproducibility, we were able to identify by consistent banding patterns 5 sibling species: Trichinella spiralis (ISS48), 2 Trichinella britovi isolates (ISS11 and ISS86), Trichinella murrelli (ISS35), Trichinella nativa (ISS71), Trichinella nelsoni (ISS29); 3 additional Trichinella genotypes: T8 (ISS149), T9 (ISS408 and ISS409), and T6 (ISS34); and the nonencapsulated species Trichinella pseudospiralis (ISS13). Moreover, 33 new Trichinella isolates from 2 zoogeographical regions were unequivocally identified. All Trichinella isolates have shown an identical pattern with those produced by the reference strain. According to these data, we have demonstrated that ISSR-PCR is a robust technique that emerges as a useful new application for the molecular identification of Trichinella isolates in epidemiological studies.

[Results the application of mitomicyn during endonasal and endocanalicular dacryocystorhinostomy by diode laser]. / Resultados de la aplicación de mitomicina en la dacriocistorrinostomía endonasal y endocanalicular con láser diodo.

AIM OF THE STUDY: To study the effects, secondary effects and security of the intrasurgical application of mitomicyn C during endonasal and endocanalicular dacryocystorhinostomy with diode laser (TLA-ELA DCR). METHODS: We carried out a randomized, prospective, interventional and double blind study in 200 patients: intrasurgical mitomicyn C was applied in 150 of then (0.4 mgr/0.2 ml) for 5 minutes by means of a polivinil acetate dressing over the osteotomy. In other 50 patients MMC was not used we followed up at 24 hours, 10 days and 1, 3 and 6 months after surgery. Endoscopic aspects and possible complications were valued. The results were compared using the Chi-squared test with the Yates correction. We looked for the presence or abscense of secondary effects in the application of mitomicyn C. RESULTS: The average follow up was 15.25 months (range 6 to 21 months). The percentages of alterations for excesive scarring were 21.77% in patients without and MAC 8.03% in the ones MMC. The difference was statisticaly significant (p = 0.02). We did not find secondary effects due to application of mitomcyn. CONCLUSIONS: Intrasurgical application of topical MMC during TLA-ENL DCR reduces the number of pathological findings due to scarring of the surrouding area of the new drainage without secondary effects.

Effect of piroxicam, metamizol, and S-adenosylmethionine in a murine model of experimental trichomoniasis.

Biological effects of piroxicam, metamizol, and S-adenosylmethionine (S-AMET) have been tested in NMRI mice infected intraperitoneally with Trichomonas vaginalis. An intraperitoneal treatment during ten preinfection days with piroxicam (10 mg/Kg/day), or metamizol (275 mg/Kg/day), but not with S-AMET (117 mg/Kg/day) induced a significant decrease of abdominal lesions and mortality, assessed by means of a pathogenicity index. The trichomonicidal activity of piroxicam, metamizol, and S-AMET was tested in vitro at the concentration of 300 microM, but found ineffective. These assays have shown the usefulness of the experimental trichomoniasis model for the study of the immunomodulating activity of synthetic drugs.

Albendazole versus ricobendazole (albendazole-sulphoxide) against enteral and parenteral stages of Trichinella spiralis in mice.

Comparison of the anthelmintic activity and pharmacokinetic profiles following albendazole (ABZ) and albendazole-sulphoxide (ricobendazole = RBZ) administration was made in a mouse model for helminthic infections. Swiss CD-1 mice were experimentally infected with Trichinella spiralis and treated with either ABZ or RBZ at 3 different stages of the parasite life-cycle: pre-adult (day 1 p.i.), migrating larvae (days 13, 14 and 15 p.i.) and encysted muscle larvae (days 34, 35 and 36 p.i.). Plasma concentrations of albendazole-sulphoxide (ABZSO) were measured in age matched non-infected mice by high performance liquid chromatography (HPLC), after administration of ABZ or RBZ dosed at 50 mg ABZ equivalent kg-1. ABZSO pharmacokinetic profiles following ABZ or RBZ administration were similar, although the Tmax (1.83 +/- 0.30 and 0.41 +/- 0.28, respectively) were significantly different (P < 0.01). Against pre-adult stages ABZ was significantly (P < 0.05) more effective than RBZ when administered at 10 mg kg-1 (96.5% and 78.0% reduction with respect to the control group). Migrating and encysted larvae were less sensitive to both compounds and dose rates had to be increased to 100 mg kg-1 to achieve significant efficacies. Against parenteral stages, ABZ was significantly more effective than RBZ when both were given at 100 mg kg-1 (64.0% and 44.2% reduction against migrating larvae and 94.7% and 65.5% reduction against encysted larvae, respectively). In conclusion, RBZ was not more effective than ABZ against enteral and parenteral stages of Trichinella spiralis.

The relationship of experimental pathogenicity in vivo with in vitro cytoadherence and cytotoxicity of 6 different isolates of Trichomonas vaginalis.

The experimental pathogenic effects in vivo and in vitro of 6 different isolates of Trichomonas vaginalis were studied following their inoculation into NMRI mice and on to adherent cultures of HeLa cells. Contact between the parasite and the adherent monolayer of cells was necessary to induce the monolayer to detach. The strains which were more virulent to mice also showed a greater weighted index of adherence; the weighted index of cytotoxicity in vitro did not, on the other hand, correlate with experimental pathology in vivo.

Vaccination of mice and sheep with Fh12 FABP from Fasciola hepatica using the new adjuvant/immunomodulator system ADAD.

We evaluate the ability of a Fasciola hepatica FABP native antigen (Fh12) with a new vaccination system called ADAD to protect mice and sheep against an experimental F. hepatica infection. The vaccination protocol consists of a set of two injections. The first injection contains a micelle in which two components are included, saponin from Quillaja saponaria (Qs) and/or Anapsos (A) a Polypodium leucotomos hydroalcoholic extract, both emulsified in a non-mineral oil (Montanide) in a water/oil emulsion (30/70). This is subcutaneously injected to achieve the "adaptation" of the immune system to subsequent stimuli. The second injection contains in addition the Fh12 antigen. Two different experiments were carried out using two mouse strains (BALB/c and CD-1). Mice vaccinated with Qs+A+Fh12 presented a survival rate of 40%, when compared with control groups. Furthermore, we evaluated the efficiency of the vaccination in sheep against an experimental F. hepatica challenge. The vaccinated sheep presented lower fluke recovery (24.5%), number of eggs in bile fluid (58.1%) and faeces (40.3%) than control groups. The recovered flukes were shorter (32.7%), immature (34.0%) and with lower body mass (31.6%) than non-complete vaccinated sheep. Thus, the new ADAD system could be a good alternative for future vaccination experiments against fasciolosis.

In vitro screening of american plant extracts on Trypanosoma cruzi and trichomonas vaginalis.

From the beginning of this decade and with the revival of the phytotherapy, biological research about immunomodulatory, anti-inflammatory and antiprotozoal effects of Central and South American plants have been in progress. Our objective was to determine the antiprotozoal activity of 79 extracts from different plant families, including Asteraceae, Araceae, Moraceae, Solanaceae, Rhamnaceae, Zingiberaceae, Leguminosae and Sapotaceae. Once matching with herbarium specimens authenticated the plants, selected parts were separated, dried carefully and reduced to powder. Most of the screened extracts were aqueous. Two protozoa with different metabolic pathways, Trypanosoma cruzi and Trichomonas vaginalis were used as experimental models. Trypanocidal activity of plants was assayed on epimastigote cultures in liver infusion tryptose (LIT). Anti-Trichomonas activity was determined over cultures of the parasite in Diamond medium. In both cases, microscopic counting of parasites, after their incubation in the presence of different concentrations of the crude extracts, were made in order to determine the cytocidal and cytostatic activities respect to control cultures. Of the nine extracts that showed antiprotozoal activity, those from Mikania cordifolia and Philodendron bipinnatifidum were then fractionated, and again, were assayed the organic and aqueous phases obtained.