Membranas amnióticas y su aplicación en el tratamiento de quemaduras: una revisión sistemática exploratoria

Las quemaduras son un problema de interés en salud pública ya que generan un alto índice de morbimortalidad a nivel mundial, las quemaduras térmicas son las más prevalentes y pueden alterar la integridad anatómica, funcional y estética de la piel, aspectos fundamentales para la autoestima del paciente y su capacidad para reintegrarse a la sociedad. Al revisar la literatura sobre el tratamiento de estas afecciones encontramos diversos tratamientos, entre ellos el uso de membrana amniótica humana, la cual ha tenido un impacto importante en el manejo de quemaduras al funcionar como andamio biológico con cualidades regenerativas y antiinflamatorias. El presente artículo tiene como objetivo sintetizar la información actual que describe las aplicaciones de membranas amnióticas humanas en quemaduras, realizamos una revisión exploratoria sistemática de la literatura desde 2010 hasta 2021.

Burns are a problem of interest in public health since they generate a high rate of morbidity and mortality worldwide, thermal burns are the most prevalent and can alter the anatomical, functional and aesthetic integrity of the skin, fundamental aspects for the patient's self-esteem and their ability to reintegrate into society. At review literature about the treatment of these conditions, we find various treatments, including the use of human amniotic membrane, which has had a significant impact on burn management by functioning as a biological scaffold with regenerative and anti-inflammatory qualities. The present article aims to synthesize the current information that describes the applications of human amniotic membranes in burns. We carry out a systematic exploratory review of the literature from 2010 to 2021.

Optical spectra of molecular aggregates and crystals: testing approximation schemes.

The interplay between exciton delocalization and molecular vibrations profoundly affects optical spectra of molecular aggregates and crystals. The exciton motion occurs on a similar timescale as molecular vibrations, leading to a complex and intrinsically non-adiabatic problem that has been handled over the years introducing several approximation schemes. Here we discuss systems where intermolecular distances are large enough so that only electrostatic intermolecular interactions enter into play and can be treated in the dipolar approximation. Moreover, we only account for interactions between transition dipole moments, as relevant to symmetric molecules, with negligible permanent (multi)polar moments in the ground and low-lying excited states. Translational symmetry is fully exploited to obtain numerically exact solutions of the relevant Hamiltonian for systems of comparatively large size. This offers a unique opportunity to assess the reliability of different approximation schemes. The so-called Heitler-London approximation, only accounting for the effects of intermolecular interactions among degenerate electronic states, leads to the celebrated exciton model, widely adopted to describe optical spectra of molecular aggregates and crystals. We demonstrate that, mainly due to a cancellation of errors, the exciton model approximates well the position of exciton bands and reasonably well the bandshapes, but it fails to predict spectral intensities, leading to underestimated intensities in J-aggregates and overestimated intensities in H-aggregates. This general result is validated against an exact sum-rule. Finally, we address the validity of several approximation schemes adopted to reduce the dimension of the vibrational basis.

High levels of p53 protein expression do not correlate with p53 mutations in hepatocellular carcinoma.

To determine the relationship between p53 altered expression and p53 mutations in hepatocellular carcinoma (HCC), we analysed p53 protein immunohistochemically and assessed the presence of mutations in exons 4-8 of the p53 gene using SSCP assay in 117 HCCs corresponding to 78 patients. We also determined the relationship of p53 expression with cellular proliferation by immunostaining with monoclonal antibodies to Ki-67. We found significant levels of p53 protein expression in 23.1% of the 117 cases studied, but identified mutations in only 12 cases (10.3%). Only four of the p53-positive cases had mutations in the regions analysed. Six of the cases that displayed mutations at p53 gene were negative for immunohistochemical analysis (IHC) and two cases showed positive immunoreactivity in the cytoplasm of the cell. In conclusion, strong IHC reactivity for p53 protein is not an indicator of the presence of p53 gene mutations at exons 4-8 in HCC. Thus, p53 loss of function in HCC should be evaluated both by p53 mutation analysis and p53 protein expression, as both give complementary information about p53 status.

Hepatocellular carcinoma: role of hepatitis B and hepatitis C viruses proteins in hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is the most important primary hepatic cancer, being a common cancer type worldwide. Many aetiological factors have been related with HCC development, such as cirrhosis, hepatitis viruses and alcohol. Chronic infection with hepatitis B (HBV) and C viruses (HCV) often results in cirrhosis and enhances the probability of developing HCC. The underlying mechanisms that lead to malignant transformation of infected cells, however, remain unclear. HBV is a DNA virus that integrates into the host genome, and this integration is believed, in part, to be carcinogenic. Besides, the virus encodes a 17 kDa protein, HBx, which is known to be a causative agent in the formation of HCC. On the contrary, HCV is a RNA virus that does not integrate into the host genome but likely induces HCC through host protein interactions or via the inflammatory response to the virus. Products encoded in the HCV genome interfere with and disturb intracellular signal transduction. Some HCV proteins, such as the core protein, NS3 and NS5A, have seen to have a regulatory effect on cellular promoters, to interact with a number of cellular proteins, and to be involved in programmed-cell death modulation under certain conditions. The identification of these proteins functions in HCC development and the subsequent development of strategies to inhibit protein-protein interactions may be the first step towards reducing the chronicity and/or of the carcinogenicity of these two viruses.

Use of cytological specimens for p53 gene alteration detection in oral squamous cell carcinoma risk patients.

AIMS: Recurrence and multifocal nature are two important characteristics of oral squamous cell carcinoma. Leukoplakia is the most frequent pre-cancerous oral lesion and, in most cases, it is not possible to predict malignant capacity. The objective of this study is to identify p53 alterations in cells taken from the oral cavity of at-risk patients. MATERIALS AND METHODS: The following samples were collected from 34 patients with oral leukoplakia with and without previous carcinoma: oral rinse, a brush swabbed over the lesions and hair roots. Mutational analysis of the p53 gene was performed by single-strand conformation polymorphisms and confirmed by DNA sequencing. RESULTS: We detected 11 mutations in p53 gene in oral cytological specimens. These alterations were observed only in brush cytology samples in patients without previous carcinoma, and in both samples (rinse and brush) in patients with previous carcinoma. Three of these patients had disease recurrence. CONCLUSION: This non-invasive technique may be useful in the follow-up of at-risk patients, and introduces new possibilities to analyse molecular markers before malignant lesions are clinically apparent.

Patterns of methylation profiles as diagnostic markers for multiple hepatocellular carcinomas.

BACKGROUND: Hepatocellular carcinoma often displays multiple tumor nodules, thus posing a problem for differential diagnosis between cancers of both multifocal and metastatic origin. Conventionally, pathological criteria have been used for this purpose, but these are largely subjective. In order to facilitate a more objective differential diagnosis of multiple HCCs, we used the patterns of methylation of p16INK4a, p14ARF, and GSTP1 genes as markers for each tumor nodule. METHODS: Sixty-seven nodules from 30 cases of multiple or recurrent HCCs were examined using methylation-specific PCR (MSP) analysis for the detection of methylation profiles. RESULTS: Hypermethylation was detected in 56.7%, 43.3% and 17.9% of the cases for p16INK4a, p14ARF, and GSTP1 genes, respectively. At the genetic level the inter-nodule methylation profiles were heterogeneous in 23 of the cases and homogeneous in another 7, enabling a multifocal origin to be diagnosed in the former and metastatic origin in the latter. CONCLUSIONS: Methylation profiling seems to be useful in differentiating the clonal origins of multiple cancers, as the information yielded by this method is essentially objective.

Gene promoter hypermethylation in oral rinses of leukoplakia patients--a diagnostic and/or prognostic tool?

Leukoplakia is the most frequent oral precancerous lesion and shows a variable rate of malignant transformation. We hypothesised that the detection of molecular alterations, like the promoter hypermethylation of DNA, in oral cytological samples from patients at risk of developing primary or recurrent tumours could be a valuable diagnostic and prognostic tool in the management of these lesions. Two groups of patients with differing risks of developing oral squamous cell carcinoma (OSCC) were analysed. DNA was extracted from the oral rinse of each patient. The methylation status of the p16, p14 and MGMT gene promoters was determined using a methylation-specific polymerase chain reaction (MSP). Methylation of p16 and MGMT was observed in 44 and 56% of the oral samples, respectively. Only 12% of the cases showed p14 methylation. DNA hypermethylation was more frequent in patients with previous OSCC. DNA promoter hypermethylation is frequent during early oral carcinogenesis and even more so in the later stages. MSP using oral rinses is a non-invasive and highly sensitive technique which could be used to monitor patients with precancerous and cancerous oral lesions.

Clinical applications of the diagnosis of p53 alterations in squamous cell carcinoma of the head and neck.

Alteration of the p53 tumor suppressor gene implies an extremely high risk of developing malignancy, and mutation of the gene is one of the most frequent genetic changes found in human cancer. Squamous cell carcinoma of the head and neck (SCCHN) shows a high incidence of p53 tumor suppressor gene alterations; the latter therefore appears to play an important role in the pathogenesis and progression of such neoplasms. The loss of p53 protein activity may be due to many p53 gene mutations or to the action of certain viruses that infect the oral cavity. Local recurrence is the most common cause of mortality after SCCHN surgery; in this sense, p53 gene mutations have been observed in tissue adjacent to the tumor, and constitute a good prognostic marker of tumor recurrence. The analysis of p53 tumor suppressor gene alterations in SCCHN affords important information on the diagnosis, prognosis and treatment of affected patients - such alterations representing an indicator in high risk patients of the convenience of applying more aggressive adjuvant therapies.

Aplicaciones clínicas del diagnóstico de las alteraciones de p53 en el carcinoma escamoso de cabeza y cuello (p53 en el CECC) / Clinical applications o f the diagnosis of p53 alterations in squamous cell carcinoma of the head and neek

La alteración del gen supresor tumoral p53 confiere un riesgo enormemente elevado de desarrollar cáncer y la mutación del mismo es uno de los cambios genéticos más frecuentemente encontrados en el cáncer humano. El carcinoma escamoso de cabeza y cuello (CECC) muestra una elevada incidencia de alteraciones en el gen supresor tumoral p53, por lo tanto parece jugar un importante papel en la patogénesis y progresión de este tipo de tumores. La pérdida de actividad de la proteína p53 puede ser debida bien a mutaciones en el gen o bien a la acción de ciertos virus que infectan la cavidad oral. La recurrencia local es la causa más común de mortalidad tras la cirugía de un CECC. En este sentido se ha observado la presencia de mutaciones del gen p53 en el tejido adyacente al tumoral siendo un buen marcador pronóstico de recurrencia. El análisis de las alteraciones del gen p53 en CECC aporta una importante información sobre el diagnóstico, pronóstico y terapia de los pacientes afectados, siendo un indicador en los pacientes de alto riesgo de la conveniencia de usar terapias adyuvantes más agresivas (AU)

Description of a project for the production and evaluation of oxygen-carrying hemosubstitutes.

Scarce availability and risk of transmission of infections and diseases (HIV, hepatitis B, Chagas' disease) limit the use and benefits of homologous blood transfusions for surgical purposes. Recent trials of perfluorocarbon-based hemosubstitutes (PFC-HSs) in experimental cardiopulmonary bypass (CPB) have demonstrated their ability to improve brain oxygenation, as compared with conventional crystalloid priming solutions. The objective of the project described here is to test different formulations of PFC-HSs and optimize their formulation and dosage for use in CPB. The project includes: (1) study the feasibility of implementing a laboratory for small scale production of PFC-HSs; (2) evaluate the efficacy of use of PFC-HSs in an animal model of CPB; and (3) evaluate the safety of use of PFC-HSs in an animal model of hemorrhagic shock. Several in-house PFC-HSs and outside PFC-HSs are being evaluated. The current state of the project is: (1) the feasibility study has been completed and several PFCs, emulsifiers and surfactants are being tested; (2) and (3) the animal models have been implemented are being used to test in-house and outside PFC-HSs as priming solutions in CPB and reinfusion fluids in hemorrhagic shock respectively. Some preliminary results are presented.

Induction of lupus inclusions by sera from patients with systemic lupus erythematosus.

A sensitive in vitro bioassay for the alpha-interferon induction of lupus-type inclusions (LI) has been established with the human B lymphoblastoid cell line, Daudi. Sera from 11 patients with systemic lupus erythematosus (SLE) were evaluated with this assay. LI induction by these sera increased in proportion to their antiviral activity on Madin-Darby bovine kidney (MDBK) cells. Two of these sera did not induce LI; they showed no antiviral activity on the MDBK cell assay. Clinically and serologically, their donors were in remission. Two sera induced the formation of LI that exceeded the maximum frequencies obtained with 3 alpha-interferon preparations. These sera had the greatest antiviral activities, and their donors had the greatest disease activities. Antisera to alpha-interferons prevented the induction of LI with the pure and homogeneous recombinant human leukocyte interferon, IFLrA, and SLE sera. Together, these results provide evidence that the alpha-interferon endogenous to SLE patients has a great ability to induce LI, and the SLE serum induction of LI corresponds well to the patient's disease activity.