Actualización práctica de diagnóstico y tratamiento de la urticaria crónica / Practical update for the diagnosis and treatment of chronic urticaria

Resumen La urticaria es un patrón distintivo de respuesta inflamatoria de piel y/o mucosas caracterizada por la aparición súbita de ronchas evanescentes, angioedema o ambos, asociados a prurito. Las formas agudas son frecuentes y se limitan a brotes de menos de 6 sema nas; mientras que las crónicas tienen una prevalencia menor al 1%, mayor duración y pueden ser espontáneas o inducibles. Los mecanismos etiopatogénicos involucrados en esta enfermedad incluyen la autoalergia, la autoinmunidad y la inflamación con la activación celular, principalmente del mastocito, lo que lleva a su degranulación con libe ración de mediadores vasoactivos. En su abordaje son fundamentales la confirmación diagnóstica; la búsqueda de indicadores de su etiopa togenia; la detección de cofactores que pueden modular su actividad; el reconocimiento de comorbilidades; la evaluación de posibles biomarcadores y, el impacto en la calidad de vida, el registro de la actividad y el control de la enfermedad. El manejo farmacológico tiene por objetivo controlar los síntomas, mientras la urticaria resuelve de forma espontánea. Este se describe de forma escalonada con una complejidad creciente.

Abstract Urticaria is a distinctive pattern of inflammatory re sponse of the skin and/or mucous membranes charac terized by the sudden appearance of vanishing wheals, angioedema, or both, associated with pruritus. Acute forms are frequent and limited to outbreaks of less than 6 weeks; while the chronic ones have a prevalence of less than 1%, longer duration and can be spontaneous or inducible. The etiopathogenic mechanisms involved in this disease include autoallergy, autoimmunity, and inflam mation with cell activation, mainly of the mast cell, leading to its degranulation with the release of vasoac tive mediators. Along its approach, diagnostic confirmation, search for indicators of its etiopathogenesis, detection of cofactors that can modulate its activity, recognition of comorbidi ties, evaluation of possible biomarkers and the assess ment of disease activity, impact and control are essential. The pharmacological management aims to control the symptoms, until the urticaria, which is self-resolv ing, is gone. This is described in a stepwise fashion with increasing complexity.

[Practical update for the diagnosis and treatment of chronic urticaria]. / Actualización práctica de diagnóstico y tratamiento de la urticaria crónica.

Urticaria is a distinctive pattern of inflammatory response of the skin and/or mucous membranes characterized by the sudden appearance of vanishing wheals, angioedema, or both, associated with pruritus. Acute forms are frequent and limited to outbreaks of less than 6 weeks; while the chronic ones have a prevalence of less than 1%, longer duration and can be spontaneous or inducible. The etiopathogenic mechanisms involved in this disease include autoallergy, autoimmunity, and inflammation with cell activation, mainly of the mast cell, leading to its degranulation with the release of vasoactive mediators. Along its approach, diagnostic confirmation, search for indicators of its etiopathogenesis, detection of cofactors that can modulate its activity, recognition of comorbidities, evaluation of possible biomarkers and the assessment of disease activity, impact and control are essential. The pharmacological management aims to control the symptoms, until the urticaria, which is self-resolving, is gone. This is described in a stepwise fashion with increasing complexity.

La urticaria es un patrón distintivo de respuesta inflamatoria de piel y/o mucosas caracterizada por la aparición súbita de ronchas evanescentes, angioedema o ambos, asociados a prurito. Las formas agudas son frecuentes y se limitan a brotes de menos de 6 semanas; mientras que las crónicas tienen una prevalencia menor al 1%, mayor duración y pueden ser espontáneas o inducibles. Los mecanismos etiopatogénicos involucrados en esta enfermedad incluyen la autoalergia, la autoinmunidad y la inflamación con la activación celular, principalmente del mastocito, lo que lleva a su degranulación con liberación de mediadores vasoactivos. En su abordaje son fundamentales la confirmación diagnóstica; la búsqueda de indicadores de su etiopatogenia; la detección de cofactores que pueden modular su actividad; el reconocimiento de comorbilidades; la evaluación de posibles biomarcadores y, el impacto en la calidad de vida, el registro de la actividad y el control de la enfermedad. El manejo farmacológico tiene por objetivo controlar los síntomas, mientras la urticaria resuelve de forma espontánea. Este se describe de forma escalonada con una complejidad creciente.

Multicenter Diagnostic Evaluation of a Novel Coronavirus Antigen Lateral Flow Test among Symptomatic Individuals in Brazil and the United Kingdom.

The COVID-19 pandemic has led to the commercialization of many antigen-based rapid diagnostic tests (Ag-RDTs), requiring independent evaluations. This report describes the clinical evaluation of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom. The collected samples (446 nasal swabs from Brazil and 246 nasopharyngeal samples from the UK) were analyzed by the Ag-RDT and compared to reverse transcription-quantitative PCR (RT-qPCR). Analytical evaluation of the Ag-RDT was performed using direct culture supernatants of SARS-CoV-2 strains from the wild-type (B.1), Alpha (B.1.1.7), Delta (B.1.617.2), Gamma (P.1), and Omicron (B.1.1.529) lineages. An overall sensitivity and specificity of 88.2% (95% confidence interval [CI], 81.3 to 93.3) and 100.0% (95% CI, 99.1 to 100.0), respectively, were obtained for the Brazilian and UK cohorts. The analytical limit of detection was determined as 1.0 × 103 PFU/mL (Alpha), 2.5 × 102 PFU/mL (Delta), 2.5 × 103 PFU/mL (Gamma), and 1.0 × 103 PFU/mL (Omicron), giving a viral copy equivalent of approximately 2.1 × 104 copies/mL, 9.0 × 105 copies/mL, 1.7 × 106 copies/mL, and 1.8 × 105 copies/mL for the Ag-RDT, respectively. Overall, while a higher sensitivity was claimed by the manufacturers than that found in this study, this evaluation finds that the Ag-RDT meets the WHO minimum performance requirements for sensitivity and specificity of COVID-19 Ag-RDTs. This study illustrates the comparative performance of the Hotgen Ag-RDT across two global settings and considers the different approaches in evaluation methods. IMPORTANCE Since the beginning of the SARS-CoV-2 pandemic, we have witnessed growing numbers of antigen rapid diagnostic tests (Ag-RDTs) being brought to market. In the United Kingdom, this was somewhat controlled indirectly as the government offered free tests from a small number of companies. However, as this has now ceased, individuals are responsible for their own acquisition of test kits. Similarly in Brazil, as of January 2022, pharmacies and other health care retailers are permitted to sell Ag-RDTs directly to the community. Many of these Ag-RDTs have not been externally evaluated, and results are not readily available to the public. Thus, there is now a need for a transparent evaluation of Ag-RDTs with both analytical and clinical evaluation. We present an independent review of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom.

A bioluminescent and homogeneous SARS-CoV-2 spike RBD and hACE2 interaction assay for antiviral screening and monitoring patient neutralizing antibody levels.

Here we describe a homogeneous bioluminescent immunoassay based on the interaction between Fc-tagged SARS-CoV-2 Spike RBD and human ACE2, and its detection by secondary antibodies labeled with NanoLuc luciferase fragments LgBit and SmBit. The assay utility for the discovery of novel inhibitors was demonstrated with a panel of anti-RBD antibodies, ACE2-derived miniproteins and soluble ACE2. Studying the effect of RBD mutations on ACE2 binding showed that the N501Y mutation increased RBD apparent affinity toward ACE2 tenfold that resulted in escaping inhibition by some anti-RBD antibodies. In contrast, while E484K mutation did not highly change the binding affinity, it still escaped antibody inhibition likely due to changes in the epitope recognized by the antibody. Also, neutralizing antibodies (NAbs) from COVID-19 positive samples from two distinct regions (USA and Brazil) were successfully detected and the results further suggest the persistence of NAbs for at least 6 months post symptom onset. Finally, sera from vaccinated individuals were tested for NAbs and showed varying neutralizing activity after first and second doses, suggesting the assay can be used to assess immunity of vaccinated populations. Our results demonstrate the broad utility and ease of use of this methodology both for drug discovery and clinical research applications.

Synergy of DNA intercalation and catalytic activity of a copper complex towards improved polymerase inhibition and cancer cell cytotoxicity.

Improving the binding of metal complexes to DNA to boost cancer cell cytotoxicity requires fine tuning of their structural and chemical properties. Copper has been used as a metal center in compounds containing intercalating ligands due to its ability to catalytically generate reactive oxygen species (ROS), such as hydroxyl radicals (OH˙). We envision the synergy of DNA binding and ROS generation in proximity to target DNA as a powerful chemotherapy treatment. Here, we explore the use of [Cu(2CP-Bz-SMe)]2+ (2CP-Bz-SMe = 1,3-bis(1,10-phenanthrolin-2-yloxy)-N-(4-(methylthio)benzylidene)propan-2-amine) for this purpose by characterizing its cytotoxicity, DNA binding, and ability to affect DNA replication through the polymerase chain reaction - PCR and nuclease assays. We determined the binding (Kb) and Stern-Volmer constants (KSV) for complex-DNA association of 5.8 ± 0.14 × 104 and 1.64 (±0.08), respectively, through absorption titration and competitive fluorescence experiments. These values were superior to those of other Cu-complex intercalators. We hypothesize that the distorted trigonal bipyramidal geometry of [Cu(2CP-Bz-SMe)]2+ allows the phenanthroline fragments to be better accommodated into the DNA double helix. Moreover, the aromaticity of these fragments increases the local hydrophobicity thus increasing the affinity for the hydrophobic domains of DNA. Nuclease assays in the presence of common reducing agents ascorbic acid, nicotinamide adenine dinucleotide, and glutathione showed the effective degradation of DNA due to the in situ generation of OH˙. The [Cu(2CP-Bz-SMe)]2+ complex showed cytotoxicity against the following human cancer cells lines A549, MCF-7, MDA-MB-231 and MG-63 with half maximal inhibitory concentration (IC50) values of 4.62 ± 0.48, 5.20 ± 0.76, 5.70 ± 0.42 and 2.88 ± 0.66 µM, respectively. These low values of IC50, which are promising if compared to that of cisplatin, are ascribed to the synergistic effect of ROS generation with the intercalation ability into the DNA minor grooves and blocking DNA replication. This study introduces new principles for synergizing the chemical and structural properties of intercalation compounds for improved drug-DNA interactions targeting cancer.

Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress.

ACE2 and TMPRSS2 are key players on SARS-CoV-2 entry into host cells. However, it is still unclear whether expression levels of these factors could reflect disease severity. Here, a case-control study was conducted with 213 SARS-CoV-2 positive individuals where cases were defined as COVID-19 patients with respiratory distress requiring oxygen support (N = 38) and controls were those with mild to moderate symptoms of the disease who did not need oxygen therapy along the entire clinical course (N = 175). ACE2 and TMPRSS2 mRNA levels were evaluated in nasopharyngeal swab samples by RT-qPCR and logistic regression analyzes were applied to estimate associations with respiratory outcomes. ACE2 and TMPRSS2 levels positively correlated with age, which was also strongly associated with respiratory distress. Increased nasopharyngeal ACE2 levels showed a protective effect against this outcome (adjOR = 0.30; 95% CI 0.09-0.91), while TMPRSS2/ACE2 ratio was associated with risk (adjOR = 4.28; 95% CI 1.36-13.48). On stepwise regression, TMPRSS2/ACE2 ratio outperformed ACE2 to model COVID-19 severity. When nasopharyngeal swabs were compared to bronchoalveolar lavages in an independent cohort of COVID-19 patients under mechanical ventilation, similar expression levels of these genes were observed. These data suggest nasopharyngeal TMPRSS2/ACE2 as a promising candidate for further prediction models on COVID-19.

Laparoscopic cytoreductive surgery and HIPEC is effective regarding peritoneum tissue paclitaxel distribution.

BACKGROUND: In some patients with peritoneal carcinomatosis, we could perform the cytoreductive surgery and the HIPEC procedure by a complete laparoscopic approach to avoid morbidity. We consider that using laparoscopic approach for performing peritoneal carcinomatosis cytoreductive surgery and HIPEC with closed CO2 recirculation technique is possible and safe, with equal efficacy to conventional methods and hemodynamic complications. OBJECTIVE: Monitoring the effectiveness of the drug distribution in a laparoscopic ctoreductive and HIPEC surgery group with CO2 recirculation respect to a closed and open HIPEC group METHODS: Porcine model that included fifteen mini-pigs. Five pigs were operated with laparoscopic approach performing a pelvic and retroperitoneal lymphadenectomy. They later received a total laparoscopic closed HIPEC with CO2 recirculation (G1). Group 2 (G2): five pigs operated by an open cytoreductive surgery and closed HIPEC technique. Group 3 (G3): five animals in which an open cytoreductive surgery and an open HIPEC technique was performed. Blood and peritoneal determinations were realized after recirculation of the drug, at 60 min using chromatographic analysis. RESULTS: G1-G2: phrenic right peritoneum, p: 0.46. Phrenic left peritoneum, p: 0.46. Pelvic peritoneum, p: 0.17. Serum paclitaxel: p: 0.01. G1-G3: phrenic right peritoneum, p: 0.34. Phrenic left peritoneum, p: 0.34. Pelvic peritoneum, p: 0.17. Serum paclitaxel G1-G3, p: 0.02. CONCLUSIONS: A total laparoscopic approach for ctoreductive surgery and closed HIPEC with CO2 recirculation may be safe and feasible. In our experimental model there was no significant difference in tissue drug distribution respect the conventional techniques and there was a less toxicity because the serum drug concentration was significantly lower with laparoscopic approach respect the other groups.

Talla, peso e índice de masa corporal en niños y niñas wichí de Formosa, Argentina / Height, weight and body mass index of Wichí children from Formosa, Argentina

Este trabajo presenta datos antropométricos descriptivos de 194 niños y niñas (0-18 años) de una población wichí de la provincia de Formosa, Argentina. El objetivo fue documentar el crecimiento y el estado nutricional de este pueblo originario. Se tomaron datos de peso, talla e índice de masa corporal y se calcularon los respectivos puntajes Z utilizando referencias nacionales e internacionales. La mayoría de los parámetros analizados caen dentro de los rangos de la normalidad. Sin embargo, es preocupante la presencia de un porcentaje significativo de niñas y niños con sobrepeso, lo cual indicaría que esta población se encuentra atravesando un proceso de occidentalización que promueve el consumo de alimentos procesados hipercalóricos y una menor actividad física.

This study provides the descriptive, anthropometric data of 194 children (aged 0-18 years) from a Wichi population located in the province of Formosa, Argentina. The objective of this study was to document growth and nutritional status in this indigenous people. Weight, height, and body mass index data were collected and the corresponding Z-scores were estimated using national and international reference standards. Most analyzed parameters were within the normal range. However, it is concerning that a significant percentage of children are overweight, which may indicate that this population is going through a process of westernization that promotes the consumption of high-calorie, highly-processed foods and a lower level of physical activity.

Height, weight and body mass index of Wichí children from Formosa, Argentina. / Talla, peso e índice de masa corporal en niños y niñas wichí de Formosa, Argentina.

This study provides the descriptive, anthropometric data of 194 children (aged 0-18 years) from a Wichi population located in the province of Formosa, Argentina. The objective of this study was to document growth and nutritional status in this indigenous people. Weight, height, and body mass index data were collected and the corresponding Z-scores were estimated using national and international reference standards. Most analyzed parameters were within the normal range. However, it is concerning that a significant percentage of children are overweight, which may indicate that this population is going through a process of westernization that promotes the consumption of high-calorie, highly-processed foods and a lower level of physical activity.

Este trabajo presenta datos antropométricos descriptivos de 194 niños y niñas (0-18 años) de una población wichí de la provincia de Formosa, Argentina. El objetivo fue documentar el crecimiento y el estado nutricional de este pueblo originario. Se tomaron datos de peso, talla e índice de masa corporal y se calcularon los respectivos puntajes Z utilizando referencias nacionales e internacionales. La mayoría de los parámetros analizados caen dentro de los rangos de la normalidad. Sin embargo, es preocupante la presencia de un porcentaje significativo de niñas y niños con sobrepeso, lo cual indicaría que esta población se encuentra atravesando un proceso de occidentalización que promueve el consumo de alimentos procesados hipercalóricos y una menor actividad física.

Growth patterns among indigenous Qom children of the Argentine Gran Chaco.

OBJECTIVES: This study describes and compares the growth strategies of rural (Western) and peri-urban (Eastern) Qom indigenous children from Argentina. METHODS: Height and weight were cross-sectionally assessed in Western (n = 263) and Eastern Qom (n = 512) individuals aged 0-18.9 years. Height-for-age (HAZ), weight-for-age (WAZ), and BMI-for-age (BMIZ) z-scores were calculated with an LMS software. Results were organized into four age categories: infancy, childhood, juvenility, and adolescence. Between-group comparisons of HAZ, WAZ, and BMIZ were carried out by age and sex categories and compared with Student's t or Mann Whitney tests. Nutritional status was classified based on BMIZ following WHO recommendations and was compared with x2 tests. RESULTS: In both groups, height and weight followed the typical human growth curve. Mean HAZ scores in both groups were within two standard deviations from the international reference, and increased from infancy to juvenility. WAZ and BMIZ scores were high during infancy and showed a general declining trend with age. Overall, Western Qom had higher HAZ scores. WAZ and BMIZ score comparisons showed only a handful of statistically significant differences, which, along with the analysis of BMI categories, indicated an association between peri-urban environments and a higher prevalence of overweight and obese individuals (P < 0.01). CONCLUSION: Among the Qom, low HAZ and high WAZ scores during the early years of development allow for the attainment of a relatively high adult stature. Their adaptive life-history strategy seems to be to divert energy toward body mass during early development, and catch-up with linear growth at a later stage of development. Am. J. Hum. Biol. 28:895-904, 2016. © 2016Wiley Periodicals, Inc.

Antiquity and geographic distribution of cranial modification among the prehistoric groups of Fuego-Patagonia, Chile.

OBJECTIVES: Nineteenth and twentieth century documents testify that four ethnic groups, generally classified as terrestrial hunters or canoe nomads, inhabited Fuego-Patagonia. Archaeologically, however, their presence and temporal depth remains unknown. This study analyzes the antiquity and geographic distribution of cranial modification, a highly visible symbol of social identity, in Fuego-Patagonia, Chile, to assess whether it expressed ethnic affiliation. MATERIALS AND METHODS: A total of 60 adult skulls from Southern Patagonia (n = 32; 53.3%) and Tierra del Fuego (n = 28; 46.7%) were examined for age-at-death, sex and cranial modification with standard methods. Individuals were further categorized as terrestrial (n = 26; 43.3%), marine (n = 21; 35%) or indetermined hunter-gatherers (n = 13; 21.7%) based on the archaeological site's characteristics, geographic location, and isotopic information. RESULTS: Thirty percent (n = 18) of the skulls in this study were modified, and most of the modified skulls (n = 15) presented a tabular-erect shape. No statistically significant differences were identified between Fuegians and Patagonians, males or females, or between the different types of adaptation and geographic locations. DISCUSSION: Thus, this Late Holocene, widely distributed practice, was not a reflection of ethnicity, but a material expression of information circulation and the complex social relations that these small-size groups had with one another. These results suggest that the emergence of modern ethnic identities in the region is a historic process that resulted from the interaction of local groups with European and Criollos.

Effect of the treatment with Achyrocline satureioides (free and nanocapsules essential oil) and diminazene aceturate on hematological and biochemical parameters in rats infected by Trypanosoma evansi.

This study aimed to verify the effect of the treatment with A. satureioides essential oil (free and nanoencapsulated forms) and diminazene aceturate on hematological and biochemical variables in rats infected by Trypanosoma evansi. The 56 rats were divided into seven groups with eight rats each. Groups A, C and D were composed by uninfected animals, and groups B, E, F and G were formed by infected rats with T. evansi. Rats from groups A and B were used as negative and positive control, respectively. Rats from the groups C and E were treated with A. satureioides essential oil, and groups D and F were treated with A. satureioides nanoencapsulated essential oil. Groups C, D, E and F received one dose of oil (1.5 mL kg(-1)) during five consecutive days orally. Group G was treated with diminazene aceturate (D.A.) in therapeutic dose (3.5 mg kg(-1)) in an only dose. The blood samples were collected on day 5 PI for analyses of hematological (erythrocytes and leukocytes count, hemoglobin concentration, hematocrit, mean corpuscular and mean corpuscular hemoglobin concentration) and biochemical (glucose, triglycerides, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, urea and creatinine) variables. A. satureioides administered was able to maintain low parasitemia, mainly the nanoencapsulated form, on 5 days post infection. On the infected animals with T. evansi treated with A. satureioides essential oil (free and nanocapsules) the number of total leucocytes, lymphocytes and monocytes present was similar to uninfected rats, and different from infected and not-treated animals (leukocytosis). Treatment with A. satureioides in free form elevated levels of ALT and AST, demonstrating liver damage; however, treatment with nanoencapsulated form did not cause elevation of these enzymes. Finally, treatments inhibited the increase in creatinine levels caused by infection for T. evansi. In summary, the nanoencapsulated form showed better activity on the trypanosome; it did not cause liver toxicity and prevented renal damage.

Meloxicam-loaded nanocapsules have antinociceptive and antiedematogenic effects in acute models of nociception.

AIMS: The development of new treatments for inflammation and pain continues to be of high interest, since long-acting effect is critical for patients. The present study investigated whether the polymeric nanocapsules, a drug delivery system, have pharmacological effect on acute nociceptive and inflammatory models in mice. MAIN METHODS: Swiss mice (20-25 g) were previously pre-treated with meloxicam-loaded nanocapsules (M-NC) or free meloxicam (M-F) or suspension without drug (B-NC), at a dose of 5 mg/kg (per oral) at different times (0.5-120 h). Antinociceptive and antiedematogenic effects were evaluated by chemical (acetic acid-induced abdominal writhing, nociception and paw edema induced by formalin and glutamate, croton oil-induced ear edema) and thermal (tail immersion and hot-plate) tests. KEY FINDINGS: M-NC reduced the licking time- and paw edema-induced by glutamate and formalin, while M-F did not have an effect. In the acetic acid-induced abdominal writhing and croton oil-induced ear edema, analysis of time-course revealed that M-NC showed a response more prolonged than M-F. In the hot-plate test, a thermal test, the time-course analysis indicated a similar increase in the latency response to thermal stimuli of M-NC and M-F, while in the tail-immersion test M-F had an effect at 0.5 h and M-NC at 24 h. SIGNIFICANCE: Polymeric nanoparticles had antinociceptive, anti-inflammatory and antiedematogenic effects in the formalin and glutamate tests, and prolonged the effect in acetic acid and croton oil tests, but not in thermal tests, supporting the idea that the inflammatory process in tissues facilitates the vectoring of polymeric nanoparticles.

Quistes vellosos eruptivos con compromiso facial: presentación de un caso / Eruptive vellus hair cyst with facial involvement: case report

Los quistes vellosos eruptivos se presentan como lesiones de 1 a 4 mm, aspecto papular, color piel, rojizo a amarillento de etiología desconocida, localizados en tórax anterior o extremidades, con menor frecuencia pueden observarse en cara, cuello, abdomen y glúteos. Representan una patología poco frecuente derivada del infundíbulo piloso que puede ocurrir esporádicamente o ser heredada de forma autosómica dominante. Aunque su principal importancia radica en el diagnóstico diferencial, la dificultad en el manejo terapéutico es otro reto en esta entidad. Se presenta un caso de quistes vellosos eruptivos con compromiso extenso en el cual consideramos de interés peculiar, la localización facial.

Eruptive vellus hair cysts are papular lesions of 1-4 mm, skin color, reddish to yellowish, of unknown etiology, located on anterior chest or extremities. Less frequent locations may be seen on face, neck, abdomen and buttocks. It is an unusual condition resulting from hair infundibulum that may occur sporadically or being inherited in autosomal dominant manner. Although its main importance lies in the differential diagnosis, therapeutic approach is another challenge in this entity. A case of eruptive vellus cyst with extensive involvement is presented, emphasizing facial location of the lesions.

Metástasis umbilical: nódulo de la Hermana María José / Umbilical metastasis: Sister Mary Joseph´s nodule

El término “nódulo de la hermana María José” se refiere a la presencia de una lesión umbilical, generalmente de larga evolución,que representa una metástasis cutánea relacionada habitualmente con una neoplasia intra abdominal. Las metástasis umbilicales se presentan por lo general tardíamente en el curso de neoplasias, coincidentes o secundarias a carcinomatosis peritoneal. Su presencia es índice de mal pronóstico ya que se relaciona con una baja sobrevida. Habitualmente, al momento del diagnóstico, los recursos terapéuticos son escasos. A continuación se presenta el caso de una paciente de sexo femenino, intervenida 4 años previos a la consulta por carcinoma de endometrio, que presenta una tumoración abdominal compatible con el diagnostico de Nódulo de la Hermana María José, resultando ser una metástasis cutánea de su neoplasia previa.

The term “Sister Mary Joseph ́s nodule” is related to the presence of a long development umbilical lesion, usually representing a cutaneous metastasis from an intraabdominal neoplasia. Umbilical metastases often are present lately in the course of neoplasias, coincident or secondary to peritoneal carcinomatosis, and are a poor prognosis indicator associated with low survival. Treatment resources are scarce at the time of diagnosis. We report a female patient, intervened four years ago because an endometrial carcinoma, with an abdominal tumor consistent with Sister Mary Joseph ́s nodule, turning out to be a cutaneous metastasis from her previous neoplasia.

Reacción evocadora de radiación por trastuzumab: revisión y reporte de un caso / Radiation recall dermatitis induced by trastuzumab: review and case report

Se presenta un caso de reacción evocadora de radiación (RER) en una paciente de 37 años con cáncer de mama estadio IIIB, que realizó 6 ciclos de quimioterapia con epidoxorubicina y docetaxel, terapia radiante y trastuzumab. Diez días después definalizada la radioterapia, desarrolló una dermatosis ampollar en la mama irradiada, coincidiendo con un ciclo de tratuzumab. El trastuzumab, anticuerpo monoclonal humanizado contra el receptor HER2, fue aprobado en 1998 por la FDA como primera línea de tratamiento paliativo para el cáncer de mama avanzado con receptores HER2 positivos y, como terapia adyuvante, en 2006. Existen pocos casos de RER por trastuzumab comunicados hasta la fecha.

A 37-year-old female patient with radiation recall dermatitis (RRD) is reported. She held 6 cycles of chemotherapy with epidoxorubicin and docetaxel, radiant therapy and trastuzumab due to stage IIIB breast cancer. Ten days after finishing radiation therapy, she developed a blistering dermatitis on irradiated breast. Trastuzumab, a humanized monoclonal antibody against the HER2 receptor, was approved in 1998 by the FDA as a first-line palliative treatment for advanced breast cancer with positive HER2 receptors and, as adjuvant therapy, in 2006. There are only few cases reported of RRD by trastuzumab up to date.

Natural lipid nanoparticles containing nimesulide: synthesis, characterization and in vivo antiedematogenic and antinociceptive activities.

Lipid nanoparticles are drug delivery systems able to increase bioavailability of poorly soluble drugs. They can be prepared with different lipid materials, especially natural lipids. Shea butter is a natural lipid obtained from the Butyrospermum parkii seed and rich in oleic and stearic acids. Nimesulide is a COX 2 selective anti-inflammatory that is poorly soluble in water. The purpose of this study was to develop and characterize shea butter lipid nanoparticles using a new technique and evaluate the in vivo activity of these nanoparticles. Lipid nanoparticles were prepared by melting shea butter and mixing with an aqueous phase using a high shear mixer. The nanoparticles presented pH of 6.9 +/- 0.1, mean particle size of 90 nm and a narrow polydispersity (0.21). Zeta potential was around -20 mV and the encapsulation efficiency was 97.5%. Drug release was evaluated using dialysis bags and presented monoexponential profile with t50% of 4.80 h (free drug t50% was only 2.86 h). Antinociceptive activity was performed by the acetic acid model. Both nimesulide and nimesulide-loaded nanoparticles presented significant activity compared to the control. The in vivo anti-inflammatory activity was evaluated by paw edema and was statistically different for the nanoparticles containing nimesulide compared to free nimesulide, blank nanoparticles and saline. In conclusion, the use of shea butter as encapsulating lipid was very successful and allowed nanoparticles to be prepared with a very simple technique. The nanoparticles presented significant pharmacological effects that were not seen for free drug administration.

Protective effect of meloxicam-loaded nanocapsules against amyloid-ß peptide-induced damage in mice.

The objective of present study was to investigate the protective effect of M-NC against aß (25-35) peptide-induced damage in mice, as the first step to evaluate their potential value for the treatment of AD. Moreover, we compared the effects of M-NC with free meloxicam (M-F). Mice were divided into six groups: (I) sham, (II) aß, (III) M-NC, (IV) M-F, (V) M-NC+aß and (VI) M-F+aß. Mice were pre-treated with M-NC (5mg/kg, by gavage), M-F (5mg/kg, by gavage) or blank nanocapsules (B-NC). Thirty minutes after treatments, aß peptide (3nmol) or filtered water were i.c.v. injected. Learning and memory were assessed with the Morris water maze (MWM) (days 4-7) and step-down-type passive-avoidance (SDPA) (days 7-8) tasks. At the end of the experimental protocol (day 8), animals were euthanized and brains were removed for biochemical determinations (reactive species (RS), non-protein thiols (NPSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST)) and histological examination. Our results confirmed that aß peptide caused learning and memory deficits in mice. Histological analysis demonstrated neuronal loss, intense cellular accumulation and chromatolysis caused by aß peptide. Furthermore, this study showed that oxidative stress was increased in mice that received aß peptide. An important finding of the present study was the protective effect of M-NC in damage induced by aß peptide. However, M-F did not have protective effect. In summary, the data reported herein clearly demonstrate that meloxicam carried by polymeric nanocapsules protected against learning and memory impairments, loss neuronal and oxidative stress in a mouse model of AD induced by aß peptide.

Astaxanthin reduces oxidative stress, but not aortic damage in atherosclerotic rabbits.

We evaluated whether carotenoid astaxanthin (ASX) could prevent oxidative and atherosclerotic damage in rabbits. Rabbits received regular chow (control) or an atherogenic diet (1% cholesterol) alone or supplemented with 50, 100, and 500 mg% ASX for 60 days (n = 5-9 per group). The atherogenic diet increased the serum cholesterol levels and the ratio of the intima/media area in the aortic arch. These changes were not prevented by ASX. Atherosclerotic rabbits showed increased aortic lipid peroxidation and nonprotein thiol group (NPSH) levels along with inhibition of glutathione peroxidase (GSH-Px). All ASX doses attenuated lipid peroxidation and the increase in NPSH but not the inhibition of GSH-Px. Aortic superoxide dismutase (SOD), catalase (CAT), and thioredoxin reductase (TrxR) activities were enhanced in atherosclerotic rabbits. Although all ASX doses prevented the increase in SOD activity, only 100 and 500 mg% ASX prevented the increase in CAT activity. Furthermore, these same doses partially prevented the increase in TrxR activity, while 50 mg% ASX completely prevented the effects of the atherogenic diet on this enzyme. However, ASX did not attenuate the hypercholesterolemia or the atherosclerotic lesions caused by the atherogenic diet at any of the doses evaluated. Our results indicate that although ASX did not prevent hypercholesterolemia or atherosclerotic lesions, it could play a beneficial role by preventing lipid peroxidation and changes in antioxidant enzyme activities.

Human skin penetration and distribution of nimesulide from hydrophilic gels containing nanocarriers.

The objective of this work was to study the in vitro skin penetration of a drug model (nimesulide) from semi-solid topical formulations containing nanospheres, nanocapsules or nanoemulsion. Nanoprecipitation, interfacial deposition and spontaneous emulsification methods were used to prepare the nanostructured suspension. The hydrodynamic diameters were 252nm for the nanoemulsion, 277nm for the nanocapsules and 202nm for the nanospheres containing nimesulide. The different nanocarrier systems were incorporated in the hydrophilic gels and their ability of delivering the drug into the human skin were investigated using stripping technique and Franz-type diffusion cells. The amount of nimesulide released into the stratum corneum (SC) from the gel containing nanocapsules (GNM-NC) and the gel containing nanospheres (GNM-NS) was similar. On the other hand, for the gel containing nanoemulsion (GNM-NE), the nimesulide was not quantified in SC, but it has been directly permeated for the dermis. The penetration of the nimesulide using the gel containing nanocapsules (GNM-NC) was larger in the deeper skin than using the gel containing nanospheres (GNM-NS) or the one containing nanoemulsion (GNM-NE). The gels containing nanocarriers (GNM-NC, GNM-NS and GNM-NE) were able to release the drug in the viable layer of the skin, comparing to a non-particulated nimesulide-loaded formulation at the same concentration.