Conjunctivitis as a sign of persistent SARS-COV-2 infection? An observational study and report of late symptoms.

PURPOSE: To investigate if symptomatic conjunctivitis during the recovery phase of the disease could be associated to a persistent presence of SARS-CoV-2 in the upper respiratory tract. Secondary end points were to analyze the presence of SARS-CoV-2 in the conjunctiva of ocular symptomatic patients and to record the presence of ocular disturbances at this point of the disease. METHODS: An observational study including consecutive COVID19 patients treated at Humanitas Clinical and Research Hospital who were attending for nasopharyngeal swab to confirm the resolution of SARS-CoV-2 infection and end of isolation. We examined 129 consecutive patients from May to June 2020. The primary end point was to determine if symptomatic conjunctivitis at this point of the disease could be associated to a persistent presence of SARS-CoV-2 in the upper respiratory tract. Secondary end points were to analyze the presence of SARS-CoV-2 in the conjunctiva of ocular symptomatic patients and to record the presence of ocular disturbances at this point of the disease. RESULTS: One hundred twenty eight patients were included, 9.38% had conjunctivitis, none resulted positive to conjunctival PCR swab test, while two of them had positive nasopharyngeal result. Mean time elapsed since the first COVID-19 positive swab to the time of examination was 6 weeks ( ± 3). The only significant association was the presence of conjunctivitis with older age (65.3 ± 12.7 vs 56.7 + 13.5. p = 0.046). Nasopharyngeal swab resulted positive in 22 patients (17.19%). While 88 patients (68.2%) did not have any ocular complain during their COVID19 disease. The 40 patients (31.8%) reporting ocular disturbances complained about: redness (25.43%), tearing (19.53%), burning (18.35%), foreign body sensation (17.18%), itching (15.62%), and discharge (12.5%). CONCLUSION: This study showed that late conjunctivitis cannot be considered as a marker of persistent infection when patients are sent to confirm the resolution of SARS-CoV-2 infection.

Monoterapia biológica en pacientes con artritis reumatoidea en Argentina / Biological monotherapy in patients with rheumatoid arthritis in Argentina

Introducción: La utilización de agentes biológicos para el tratamiento de la Artritis Reumatoidea (AR) es habitualmente usada en aquellos pacientes con enfermedad activa que no hayan respondido al tratamiento con drogas modificadoras de la Artritis Reumatoidea convencionales (DMARD, por sus siglas en inglés) o que hayan presentado intolerancia a las mismas. Al estado actual de la evidencia, la terapia combinada de agentes biológicos más un DMARD convencional (principalmente metotrexato) constituye el estándar de tratamiento. Sin embargo existen algunos escenarios como la intolerancia, la falta de adherencia y la aparición de eventos adversos a las DMARDs convencionales donde la monoterapia biológica emerge como una opción terapéutica válida. Según los distintos registros a nivel internacional, la frecuencia de utilización de agentes biológicos en monoterapia oscila entre 12 a 39%. Debido a la ausencia de estos datos a nivel local decidimos realizar este estudio para conocer el porcentaje de pacientes que se encuentran en monoterapia biológica y analizar las causas que llevaron a este tipo de tratamiento. Materiales y métodos: Estudio de tipo corte transversal donde se invitó a participar a diferentes centros reumatológicos distribuidos a lo largo de Argentina. Cada centro revisó las historias clínicas de los últimos 30 a 50 pacientes consecutivos vistos con AR, mayores de 18 años, que habían presentado inadecuada respuesta al tratamiento con DMARDs y que estaban bajo tratamiento biológico. Se completaba una ficha por cada paciente incluido, registrando datos demográficos, de la enfermedad y tratamientos previos. Resultados: Se incluyeron 32 centros y se evaluaron 1148 historias clínicas de pacientes con AR durante el mes de octubre y noviembre del 2012. Un 21,4% (246) de los pacientes al momento del estudio se encontraba bajo tratamiento biológico en monoterapia...

Introduction: The use of biological agents for the treatment of rheumatoid arthritis (RA) is commonly used in patients with active disease who have not responded to treatment with conventional rheumatoid arthritis-modifying drugs (DMARDs) or Who have presented intolerance to them. At the present state of evidence, combined therapy of biological agents plus conventional DMARD (mainly methotrexate) is the standard of treatment. However, there are some scenarios such as intolerance, lack of adherence and the appearance of adverse events to conventional DMARDs where biological monotherapy emerges as a valid therapeutic option. According to different international registries, the frequency of use of biological agents in monotherapy ranges from 12 to 39%. Due to the absence of these data at the local level we decided to carry out this study to know the percentage of patients who are in biological monotherapy and to analyze the causes that led to this type of treatment. Materials and methods: A cross-sectional study where different rheumatologic centers throughout Argentina were invited to participate. Each center reviewed the medical records of the last 30 to 50 consecutive patients seen with RA, older than 18 years, who had inadequate response to treatment with DMARDs and who were under biological treatment. One card was completed for each patient included, recording demographic, disease and previous treatment data. Results: Thirty-two centers were included and 1148 clinical records of patients with RA were evaluated during October and November 2012. A total of 244 patients (246) at the time of the study were under monotherapy...

Heterologous rRNA gene expression: internal fragmentation of Sciara coprophila 28S rRNA within microinjected Xenopus laevis oocytes.

Species-specific pre-rRNA processing variations may result in fragmented 18S, 5.8S and 28S rRNAs. Some insect 5.8S and 28S rRNAs are further cleaved, creating within a 'hidden break' or 'gap'. We investigated the specificity of the processing mechanism by microinjecting Sciara coprophila (fungus fly) rDNA into Xenopus laevis oocytes to examine insect rRNA maturation within a cell where endogenous rRNAs are not cleaved at homologous sites. Results confirm insect rDNA transcription and pre-28S rRNA fragmentation, demonstrating that fly-specific processing machinery is not required. Instead, oocytes may provide required accessory factors, suggesting that the insect gap processing mechanism is served by an evolutionarily conserved apparatus. Alternatively, these results may suggest that processing in some lineages is an autocatalytic property of the rRNA.

Life and death of a cardiac myocyte: principles of cellular biology.

If the future of extracorporeal circulation is to include approaches to enhance localized or widespread distribution of cells, and/or gene transfer for augmentation of cardiac function, it is imperative that we gain an increased understanding of the mechanisms that define the cardiac myocyte phenotype. The purpose of this paper is to review the natural history of the cardiac myocyte. A variety of signals determine the cellular processes that characterize birth, growth, differentiation and death of cardiomyocytes. Examined here are primary aspects of the molecular genetics of growth and development, including signal transduction, protein phosphorylation, the cell division cycle, and transcriptional activation. This review is intended to be an update on insights into molecular aspects of the cell, with emphasis on gene expression during cardiac myogenesis and a discussion of its relevance to the field of extracorporeal circulation. In addition, the current status of research in myogenesis is presented.

Research on anti-HIV-1 agents. Investigation on the CD4-Suradista binding mode through docking experiments.

Sulfonated distamycin (Suradista) derivatives exhibit anti-HIV-1 activity by inhibiting the binding of the viral envelope glycoprotein gp120 to its receptor (CD4). With the aim to propose a possible binding mode between Suradistas and the CD4 macromolecule, molecular docking experiments, followed by energy minimization of the complexes thus obtained, were performed. Computational results show that ligand binding at the CD4 surface involves two or three positively charged regions of the macromolecule, in agreement with the results of X-ray crystallographic analysis of a ternary complex (CD4/gp120/neutralizing antibody) recently reported in the literature. Our findings account well for the structure-activity relationship found for Suradista compounds.

Molecular advances in cardiac and cardiovascular disease.

Recent advances in the field of molecular biology have led to a better understanding of the pathological mechanisms of cardiovascular disease. The impact of these findings will shape the future of treatment modalities for cardiovascular disorders. Postulated targets and biological rationale of new techniques are being developed in a race towards molecular therapies for vascular diseases. Whether it is modulation of transmembrane cell receptors or phenotypic changes via vectors that mediate gene transfer, there is no doubt that molecular strategies will be an integral part of the future. Here we examine past and recent perspectives, describe directions and challenges in cardiac and cardiovascular areas of research, and discuss relevance to the field of cardiovascular perfusion.

Synthesis and binding mode of heterocyclic analogues of suramin inhibiting the human basic fibroblast growth factor.

The design, synthesis, and biological evaluation of a series of pyrrole and pyrazole congeners 2 of suramin, directed toward the development and identification of new ligands that complex the human fibroblast growth factor (bFGF), thereby inhibiting tumor-promoted angiogenesis, is reported. Compounds 2 were evaluated for their ability to inhibit binding of bFGF to its receptor, in vivo bFGF-induced angiogenesis, and neovascularization of the chorioallantoic membrane in comparison with suramin. These assays showed that ligands 2 exhibit moderate to good activity, comparable to that of suramin, and are less toxic than suramin itself. In this study, affinity data of ligands in combination with the crystal structure of bFGF were used to explain structure-affinity relationships and to gain an insight into the possible mode of ligand-protein interaction. Due to the lack of experimental structural data on the ligand-bFGF complexes, molecular mechanics techniques were used to obtain putative bioactive conformations and to generate docked complexes with the three-dimensional structure of bFGF. These experiments led to suggest that compounds 2 give rise to 1:1 complexes with bFGF through an unprecedented, bidentate attachment of their naphthylsulfonate groups to two main domains, commonly referred to as the heparin binding site and the receptor binding site, on bFGF, thus preventing the interaction of the growth factor with its receptor.

Lipoproteins and coagulation.

A broad range of molecular and cellular interactions contribute to various pathophysiological alterations in haemostasis. Recent studies have shown strong links between lipoproteins and coagulation factors. Findings suggest that lipoproteins play an important role in the fibrinolytic and thrombogenic mechanisms that influence the risks of patients in acute coronary syndromes. We will examine specific aspects of lipoproteins with reference to the effects of hyperlipidaemia on endothelial dysfunction and haemostasis, and its relevance in the patient presenting for revascularization.

Lipoproteins in heart disease.

Most lipids are carried in the circulation by lipoproteins. Lipoproteins and their associated proteins, called apolipoproteins, are currently being studied in an effort to further our understanding of atherosclerotic cardiovascular disease. Lipoprotein assembly, secretion, transportation, modification and clearance are essential elements of healthy lipid metabolism. When one or more of these key steps becomes altered, various disease states are induced. Current data suggest that lipoprotein(a), a low density lipoprotein (LDL)-like particle, is an acute phase reactant that plays a critical role in the modulation of fibrinolysis. Several aspects of lipoproteins and lipoprotein metabolism will be examined. Emphasis will be placed on the proatherogenic and thrombogenic effects of oxidized LDL.

Novel sulfonated and phosphonated analogs of distamycin which inhibit the replication of HIV.

A series of novel distamycin-related polyanionic compounds were compared for their anti-HIV activity. Several were highly potent inhibitors of HIV virus-induced cell killing and viral replication of a wide variety of laboratory isolates, as well as a monocytotropic virus and a clinical isolate in human peripheral blood lymphocytes. These compounds are structurally different from other sulfonic acid containing compounds reported to be potent inhibitors of the human immunodeficiency virus (HIV) in two respects: (1) they are structurally related to the non-toxic minor groove DNA binder distamycin; and (2) a number of them contain the aromatic phosphonic acid group. The compounds that were evaluated can be categorized into monomeric or dimeric ureido structural classes incorporating the bisamido-N-methylpyrrolenaphthalene-sulfonic acid group, with differences in the number and position of the sulfonic acids on the naphthalene rings. Broader structure-activity studies were made possible through the synthesis and evaluation of the compounds containing only a single N-methylpyrrole unit, those incorporating the N-methylpyrazole structure, and compounds having the isosteric phosphonic acid group substituted for the sulfonic acid group. One of the most potent of the inhibitors was 2,2'[4,4'[[aminocarbonyl]amino]bis[N,4'-di[pyrrole-2-carboxamide- 1,1'-dimethyl]]-4,6,8 naphthalenetrisulfonic acid] hexasodium salt, NSC 651015. This compound, the phosphonic acid analog NSC 662162, and the monomeric compound NSC 651018 were studied to determine the mechanism of their inhibitory activity. Mechanistic studies revealed that inhibition was due to the disruption of virus attachment to CD(4+)-susceptible cells and a further restraint on fusion of virus and cell membranes. The relative tolerance of these compounds in mice suggests that sufficient antiviral concentrations could be reached in vivo and thus may prove valuable in the treatment of AIDS patients.

[Pleural effusion: diagnostic usefulness of pleural puncture biopsy]. / Derrame pleural: utilidad diagnóstica de la punción biopsia pleural.

To assess the diagnostic usefulness of thoracocentesis with pleural needle biopsies, we retrospectively studied 316 procedures performed in 254 patients between 1977 and 1984. Of these, 130 were ultimately found to have pleural malignant disease, with a diagnostic cytologic study in 60% of the patients, a positive pleural biopsy in 52.30% and both methods combined in 81.53% of the patients. The marginal gains from pleural biopsy in the presence of negative cytology results were 63.46%. In 59 patients, the primary neoplasm was lung cancer, the most frequent tumor (45.30%); in second place, 30 patients presented carcinoma of the breast (23%). Needle biopsy of the pleura proved to be nonspecific for the diagnosis of nonmalignant diseases except for tuberculous pleurisy: in our study 55 patients presented tuberculosis (21.65%) and in 35 of them, the pleural biopsy was characteristic. The culture of pleural fluid revealed Koch bacillus in 5.45% of these patients. Routine culture of biopsy specimen for tubercle bacillus was not carried out. Complications occurred in 4.4% of needle biopsies, with no death.

Derrame pleural: utilidad diagnostica de la puncion biopsia pleural / Diagnostic usefulness of needle biopsy in pleural effusion

Se estudiaron en forma retrospectiva los resultados de 316 punciones biopsia pleural (PBP) efectuada a 254 pacientes entre 1977 y 1984 con el objetivo de establecer su utilidad diagnóstica. En 130 (51,80%) el diagnóstico definitivo fue derrame pleural (DP) secundario a neoplasia, habiendo sido positivo el examen citológico del líquido pleural (LP) en el 60% de los casos, la biópsia pleural (BP), en el 52,30% y combinando ambos métodos en el 81,53% de los pacientes. El beneficio adicional que brindó la BP en los derrames neoplásicos con examen citológico negativo fue del 63,46%. El cáncer primitivo más frecuente fue el de pulmón en 59 pacientes (45,38%), y en segundo lugar el de mama, en 30 pacientes (23%). La tuberculosis (TBC) además del cáncer fue la única enfermedad diagnosticada mediante la PBP, en 55 pacientes (21,65% de los cuales 35 (63,63%) tuvieron una biopsia pleural característica. No se efectuó en forma rutinaria cultivo para bacilo de Koch del material de biópsia y el cultivo del LP desarrolló solo en un 5,45% de los casos de TBC. Se observaron complicaciones en el 4,4% de las punciones, ninguna fatal

Derrame pleural: utilidad diagnóstica de la punción biopsia pleural. / [Pleural effusion: diagnostic usefulness of pleural puncture biopsy]

To assess the diagnostic usefulness of thoracocentesis with pleural needle biopsies, we retrospectively studied 316 procedures performed in 254 patients between 1977 and 1984. Of these, 130 were ultimately found to have pleural malignant disease, with a diagnostic cytologic study in 60

of the patients, a positive pleural biopsy in 52.30

and both methods combined in 81.53

of the patients. The marginal gains from pleural biopsy in the presence of negative cytology results were 63.46

. In 59 patients, the primary neoplasm was lung cancer, the most frequent tumor (45.30

); in second place, 30 patients presented carcinoma of the breast (23

). Needle biopsy of the pleura proved to be nonspecific for the diagnosis of nonmalignant diseases except for tuberculous pleurisy: in our study 55 patients presented tuberculosis (21.65

) and in 35 of them, the pleural biopsy was characteristic. The culture of pleural fluid revealed Koch bacillus in 5.45

of these patients. Routine culture of biopsy specimen for tubercle bacillus was not carried out. Complications occurred in 4.4

of needle biopsies, with no death.

Derrame pleural: utilidad diagnostica de la puncion biopsia pleural / Diagnostic usefulness of needle biopsy in pleural effusion

Se estudiaron en forma retrospectiva los resultados de 316 punciones biopsia pleural (PBP) efectuada a 254 pacientes entre 1977 y 1984 con el objetivo de establecer su utilidad diagnóstica. En 130 (51,80%) el diagnóstico definitivo fue derrame pleural (DP) secundario a neoplasia, habiendo sido positivo el examen citológico del líquido pleural (LP) en el 60% de los casos, la biópsia pleural (BP), en el 52,30% y combinando ambos métodos en el 81,53% de los pacientes. El beneficio adicional que brindó la BP en los derrames neoplásicos con examen citológico negativo fue del 63,46%. El cáncer primitivo más frecuente fue el de pulmón en 59 pacientes (45,38%), y en segundo lugar el de mama, en 30 pacientes (23%). La tuberculosis (TBC) además del cáncer fue la única enfermedad diagnosticada mediante la PBP, en 55 pacientes (21,65% de los cuales 35 (63,63%) tuvieron una biopsia pleural característica. No se efectuó en forma rutinaria cultivo para bacilo de Koch del material de biópsia y el cultivo del LP desarrolló solo en un 5,45% de los casos de TBC. Se observaron complicaciones en el 4,4% de las punciones, ninguna fatal (AU)

The effect of DMSO treatment on the performance of [99mTc]HEDP.

The effect of treating a commercial skeletal imaging kit containing hydroxyethylidene diphosphonate (HEDP) with dimethyl sulfoxide (DMSO) prior to labeling with sodium pertechnetate, 99mTc[TcO4-], was investigated. Statistically, significant differences (P less than 0.05) in soft tissue retention (blood and muscle) were seen in rats after injection with the DMSO-treated HEDP compared to the nontreated HEDP. Based on i.r. and HPLC data, it appears that DMSO acts as an extractant for certain Sn2+-HEDP complexes which contribute to greater soft-tissue retention.