Curcumin Attenuates Doxorubicin-Induced Cardiac Oxidative Stress and Increases Survival in Mice.

Doxorubicin (DOX) is a potent chemotherapeutic agent used to treat multiple types of cancer, but its clinical application is limited by cardiotoxicity, mainly due to oxidative stress. Curcumin (CUR) is a natural polyphenolic compound with strong antioxidant properties, but its potential protective effects against DOX-induced cardiotoxicity need further investigation. This study aimed to evaluate CUR's efficacy in mitigating DOX-induced oxidative stress in the hearts of BALB/c mice. Mice received a DOX dose of 9 mg/kg or 16 mg/kg; half of the mice received daily doses of 100 mg/kg CUR for 15 days. Survival analysis, histopathological examination, and oxidative stress markers were assessed to determine the cardioprotective effects of CUR. Results showed that CUR significantly reduced oxidative damage and improved survival rates, particularly at the lower DOX dose (9 mg/kg). Mice treated with DOX-9 mg/kg plus CUR showed improved health conditions and reduced levels of reactive oxygen species (ROS), lipid peroxidation, sulfhydryl production, and protein carbonylation. Histopathological analysis confirmed reduced cardiac tissue damage. In conclusion, CUR combined with a lower dose of DOX effectively reduces oxidative stress and cardiac injury, enhancing survival in BALB/c mice. These findings suggest that CUR is a promising adjunct therapy to mitigate DOX-induced cardiotoxicity, potentially improving the DOX therapeutic index in cancer treatment.

Antiprotozoal, Anthelmintic and Antivectorial Activities of Titanium Dioxide Nanoparticles.

Nanotechnology has been established as a promising alternative for treating a myriad of disease-causing microorganisms that pose threats to human health. The utilization of nanoparticles (NPs) emerges as a strategy to enhance the therapeutic arsenal against these diseases, especially given the tendency of many pathogens to develop resistance to conventional medications. Notably, titanium dioxide nanoparticles (TiO2NPs) have garnered attention for their multifaceted biomedical applications, encompassing antibacterial, antifungal, antiviral, anticancer, antioxidant, and drug delivery properties. This review focuses on the cutting-edge potential of TiO2NPs against helminths, protozoa, and vectors, underscoring their pivotal role in combating these health-threatening agents.

Toxicity Assessment of New Ag-ZnO/AgO Nanocomposites: An In Vitro and In Vivo Approach.

Zinc oxide nanoparticles (ZnO NPs) are metal oxide nanomaterials, which are important for several applications: antibacterial, anthelmintic, antiprotozoal and antitumoral, among others. These applications are mainly related to the ability to spontaneously produce and induce the production of reactive oxygen species that are important components for the destruction of pathogens and tumor cells. While trying to potentiate ZnO NPs, studies have associated these NPs with silver oxide (AgO) or silver (Ag) NPs. It has already been reported that this combination (Ag-ZnO/AgO NPs) is able to enhance the microbicidal potential. Although possessing much potential for several purposes, it is important to evaluate whether this association also poses the risk of toxicity to cells and experimental models. Therefore, this work aimed to evaluate the toxicity of various Ag-ZnO/AgO NP nanocomposites, in vitro and in vivo. Accordingly, ZnO nanocrystals and nanocomposites with various concentrations of AgO (ZnO:5Ag, ZnO:9Ag or ZnO:11Ag) were used in different cytotoxicity models: Galleria mellonella (G. mellonella), cell lines (VERO and RAW 264.7) and C57BL/6 mice. In the G. mellonella model, four concentrations were used in a single dose, with subsequent evaluation of mortality. In the case of cells, serial concentrations starting at 125 µg/mL were used, with subsequent cytotoxicity assessment. Based on the safe doses obtained in G. mellonella and cell models, the best doses were used in mice, with subsequent evaluations of weight, biochemistry as also renal and liver histopathology. It was observed that the toxicity, although low, of the nanocomposites was dependent upon the concentration of AgO used in association with ZnO NPs, both in vitro and in vivo.

The Influence of IL-11 on Cardiac Fibrosis in Experimental Models: A Systematic Review.

Fibrosis is one of the main factors that impair the function of many organs. In the heart, fibrosis leads to contractile dysfunction and arrhythmias, which are important in the development of heart failure. Interleukin (IL)-11 is regulated in various heart diseases and has recently been reported to be an important cytokine in fibrosis in this organ. However, this topic has been little explored, and many questions persist. Thus, this systematic review aimed to report on possible IL-11 therapies evaluated in rodent model-induced cardiac fibrosis. Inclusion criteria were experimental in vivo studies that used different rodent models for cardiac fibrosis associated with IL-11 interventions, without year and language restrictions. The search in PubMed, Web of Science, and Embase databases was performed in October 2022. The risk of bias assessment of the studies was based on the guidelines of the SYRCLE tool, and data from the selected articles were also presented in a table as a narrative description. This review was based on eight studies in which five different interventions were used: recombinant human IL-11 (rhIL-11), anti-IL11 (X203), recombinant mouse IL-11 (rmIL-11), lentivirus (LV)-IL-11 + lutein, and anti-IL11RA (X209). Based on the included studies, the results were variable, with IL-11 overexpression inducing cardiac fibrosis, while inhibition protected against this process, preserving the function of this organ. Therefore, IL-11 stands out as a promising therapeutic target for cardiac fibrosis. However, further studies are needed to understand the mechanisms triggered by each treatment, as well as its safety and immunogenicity.

Metallic nanoparticles and treatment of cutaneous leishmaniasis: A systematic review.

BACKGROUND: Cutaneous leishmaniasis (LC) is an infectious vector-borne disease caused by parasites belonging to the genus Leishmania. Metallic nanoparticles (MNPs) have been investigated as alternatives for the treatment of LC owing to their small size and high surface area. Here, we aimed to evaluate the effect of MNPs in the treatment of LC through experimental, in vitro and in vivo investigations. METHODS: The databases used were MEDLINE/ PubMed, Scopus, Web of Science, Embase, and Science Direct. Manual searches of the reference lists of the included studies and grey literature were also performed. English language and experimental in vitro and in vivo studies using different Leishmania species, both related to MNP treatment, were included. This study was registered in PROSPERO (CRD42021248245). RESULTS: A total of 93 articles were included. Silver nanoparticles are the most studied MNPs, and L. tropica is the most studied species. Among the mechanisms of action of MNPs in vitro, we highlight the production of reactive oxygen species, direct contact of MNPs with the biomolecules of the parasite, and release of metal ions. CONCLUSION: MNPs may be considered a promising alternative for the treatment of LC, but further studies are needed to define their efficacy and safety.

Antibiotic resistance of Staphylococcus aureus isolated from the oral cavity of paraguayan participants from Coronel Oviedo, year 2021

A cross-sectional study was carried out to identify the resistance profile of Staphylococcus aureus colonizing the oral cavity of patients. Sampling was carried out with sterile swabs. Mannitol-positive colonies were cultured on blood agar, identifying S. aureus by conventional biochemical tests that included positive results for catalase, coagulase, DNAse and latex agglutination test for S. aureus. The resistance to 11 antibiotics was tested. Forty-three subjects were included; 83.7% presented oral pathologies, and 6.9% had a history of hospitalization, 18.6% mentioned having used antibiotics in the last three months. S. aureus was isolated in 3 patients; the 3 isolates presented resistance to penicillin, while 2 of the three isolates were resistant to oxacillin and cefoxitin. Resistance to erythromycin and clindamycin was also present in one patient. Two of the cases presented resistance to various drugs and didn´t report any risk factors.

Se realizó un estudio transversal para identificar el perfil de resistenia de S. aureus que se encuentra colonizando la cavidad bucal de los pacientes. La toma de muestras se realizó con hisopos estériles. Se cultivaron colonias positivas a manitol en agar sangre, identificándose S. aureus mediante pruebas bioquímicas convencionales que incluyeron resultados positivos para catalasa, coagulasa, ADNasa y aglutinación en látex para S. aureus. Se probó la resistencia a 11 antibióticos. Se incluyeron cuarenta y tres sujetos; el 83,7% presentó patología bucal y el 6,9% tenía antecedentes de hospitalización, el 18,6% mencionó haber utilizado antibióticos en los últimos tres meses. Se aisló S. aureus en 3 pacientes; los 3 aislados presentaron resistencia a penicilina, mientras que 2 de los tres aislados fueron resistentes a oxacilina y cefoxitina. Un paciente también presentó resistencia a eritromicina y clindamicina. Dos de los casos presentaron resistencia a diversos fármacos, sin haber reportado factores de riesgo.

RNA vaccines in infectious diseases: A systematic review.

Infectious diseases are a major health concern worldwide, especially as they are one of the main causes of mortality in underdeveloped and developing countries. Those that are considered emerging and re-emerging are characterized by unpredictability, high morbidity and mortality, exponential spread, and substantial social impact. These characteristics highlight the need to create an "on demand" control method, with rapid development, large-scale production, and wide distribution. In view of this, RNA vaccines have been investigated as an effective alternative for the treatment and prevention of infectious diseases since they can meet those needs and are considered safe, affordable, and totally synthetic. Therefore, this systematic review aimed to evaluate the use of RNA vaccines for infectious diseases from experimental, in vivo, and in vitro studies. PubMed, Web of Science, and Embase were searched for suitable studies. Additionally, further investigations, such as grey literature checks, were performed. A total of 723 articles were found, of which only 41 met the inclusion criteria. These studies demonstrated the potential of using RNA vaccines to control 19 different infectious diseases, of which COVID-19 was the most studied. Similarly, viruses comprised the largest number of reported vaccine targets, followed by protozoa and bacteria. The mRNA vaccines were the most widely used, and the intramuscular route of administration was the most reported. Regarding preclinical experimental models, mice were the most used to evaluate the impact and safety of the RNA vaccines developed. Thus, although further studies and evaluation of the subject are necessary, it is evident that RNA vaccines can be considered a promising alternative in the treatment and prophylaxis of infectious diseases.

Cannabis sativa: A look at protozoa, helminths, insect vectors, and pests.

Active principles extracted from plants, such as essential oils, have been commonly described in the literature as therapeutic targets for numerous pathological conditions. Cannabis sativa, which has an ancient and peculiar history, has been used for various purposes, from recreational to compounds of pharmacotherapeutic and industrial importance, such as pesticides based on this plant. It is a plant that contains approximately 500 described cannabinoid compounds and is the target of in vitro and in vivo studies at different locations. This review clarifies the role of cannabinoid compounds in parasitic infections caused by helminths and protozoa. In addition, this study briefly presented the use of C. sativa constituents in the formulation of pesticides for vector control, as the latter topic is justified by the economic burden faced by several regions where vector-borne diseases are a troubling reality. Studies involving cannabis compounds with pesticidal potential should be encouraged, especially those that evaluate their effectiveness against the different life cycles of insects, seeking to interrupt vector proliferation after egg laying. Actions aimed at the management and cultivation of plant species with ecologically correct pharmacotherapeutic and pesticide potentials are becoming urgent.

Polymethylmethacrylate Microspheres are Immunologically Inert in Mouse Tissues.

Nowadays, aesthetic concerns have gained attention, especially by patients looking for a less invasive alternative to minor facial corrections. Polymethylmethacrylate (PMMA) is widely used as a soft tissue filler; the demand for this polymer has increased, and along with it, there are some reports of adverse reactions. Such adverse reactions stem from consequences of immune and inflammatory reactions to PMMA. Some animal models have been used to unravel the causes of these reactions, among other factors involving the management of PMMA. The aim of this study was to determine the immunogenic profile of PMMA implantation in different anatomical planes of mice, over up to 360 experimental days. In this study, BALB/c mice were divided into 30 groups for immune evaluation of the interaction between the organism and the polymer; 2% PMMA was implanted subcutaneously, 10% intramuscularly and 30% in periosteal juxtaposition and followed during five experimental days (7, 30, 90, 180 and 360 days after implantation-DAI). Pro- and anti-inflammatory cytokines (IL-2, IL-4, IL-6, IFN-gamma, TNF, IL-17A, IL-10 and TGF-beta) were quantified in all experimental days. There was no statistical difference between the groups analyzed considering the evaluated parameters. Therefore, at all implanted depths, PMMA behaved inertly in a murine model.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Revision of Polymeric Nanoparticles as a Strategy to Improve the Biological Activity of Melatonin.

Drug delivery systems based on nanotechnology exhibit a number of advantages over traditional pharmacological formulations. Polymeric nanoparticles are commonly used as delivery systems and consist of synthetic or natural polymers that protect drugs from degradation in physiological environments. In this context, indolamine melatonin has been associated with several biological functions, including antioxidant, antitumor, immunoregulatory, neuroprotective, and cardioprotective effects. However, its availability, half-life, and absorption depend upon the route of administration, and this can limit its therapeutic potential. An alternative is the use of polymeric nanoparticle formulations associated with melatonin to increase its bioavailability and therapeutic dose at sites of interest. Thus, the objective of this review is to provide a general and concise approach to the therapeutic association between melatonin and polymeric nanoparticles applied to different biological disorders and to also highlight its advantages and potential applications compared to those of the typical drug formulations that are available.

Role of Ape1 in Impaired DNA Repair Capacity in Battery Recycling Plant Workers Exposed to Lead.

Exposure to lead in environmental and occupational settings continues to be a serious public health problem. At environmentally relevant doses, two mechanisms may underlie lead exposition-induced genotoxicity, disruption of the redox balance and an interference with DNA repair systems. The aim of the study was to evaluate the ability of lead exposition to induce impaired function of Ape1 and its impact on DNA repair capacity of workers chronically exposed to lead in a battery recycling plant. Our study included 53 participants, 37 lead exposed workers and 16 non-lead exposed workers. Lead intoxication was characterized by high blood lead concentration, high lipid peroxidation and low activity of delta-aminolevulinic acid dehydratase (δ-ALAD). Relevantly, we found a loss of DNA repair capacity related with down-regulation of a set of specific DNA repair genes, showing specifically, for the first time, the role of Ape1 down regulation at transcriptional and protein levels in workers exposed to lead. Additionally, using a functional assay we found an impaired function of Ape1 that correlates with high blood lead concentration and lipid peroxidation. Taken together, these data suggest that occupational exposure to lead could decrease DNA repair capacity, inhibiting the function of Ape1, as well other repair genes through the regulation of the ZF-transcription factor, promoting the genomic instability.

Analysis of visual disability in Buenos Aires, Argentina. Pathologic myopia is the leading cause in working age.

This study assessed the causes of visual impairment over a decade in Buenos Aires City. This is a retrospective case series where we reviewed the database of visual disability certificates issued by the Buenos Aires City Ministry of Health between 2009 and 2017. In Argentina, visual disability is defined as a visual acuity = 20/200 in the better eye, or a corresponding visual field of less than 20 degrees in the less impaired eye. The database included the following variables: year of issue, age, gender, and cause of visual disability. Between 2009 and 2017 a total of 7656 subjects were certified as legally blind. The mean age of the sample was 57 ± 21 years and 52.1% were females. The emission was near 700 certificates per year. The age distribution showed that 62.8% of certificates were from patients older than 50 years and that only 6.6% were given to subjects under 20. The leading causes of visual disability in Buenos Aires City were age-related macular degeneration (ARMD) with a rate of 15.5%, degenerative myopia (14.4%), primary open-angle glaucoma (11.3%) and diabetic retinopathy (6.6%). In subjects younger than 50, degenerative myopia was the first cause of visual disability. Interestingly in Argentina, where the prevalence of myopia is low, degenerative myopia is found to be the major cause of visual disability in middle-aged adult subjects. Population and clinical methods to avoid this preventable disease should need to be implemented as a matter of urgency.

Este trabajo estudia las causas de la discapacidad visual durante una década en la Ciudad de Buenos Aires. Se presenta una serie de casos retrospectiva donde se revisó la base de datos de certificados de discapacidad visual emitidos por el Ministerio de Salud de la Ciudad de Buenos Aires entre 2009 y 2017. En Argentina, la discapacidad visual se define como una agudeza visual = 20/200 en el mejor ojo, o un campo visual correspondiente de menos de 20 grados en el ojo menos deteriorado. La base de datos incluyó las siguientes variables: año de emisión, edad, sexo y causa de la discapacidad visual. Entre 2009 y 2017 se certificaron un total de 7656 sujetos con ceguera legal. La edad media de la muestra fue de 57 ± 21 años y el 52.1% fueron mujeres. La distribución por edades mostró que el 62.8% de los certificados fueron dados a pacientes mayores de 50 años y que solo el 6.6% se otorgó a menores de 20 años. Las principales causas de discapacidad visual fueron la degeneración macular asociada a la edad (DMAE) (15.5%), la miopía degenerativa (14.4%), el glaucoma primario de ángulo abierto (11.3%) y la retinopatía diabética (6.6%). En los menores de 50 años, la miopía degenerativa fue la primera causa de discapacidad visual. Resulta interesante que, en Argentina, donde la prevalencia de miopía es baja, la miopía degenerativa sea la principal causa de discapacidad visual en adultos de mediana edad.

Analysis of visual disability in Buenos Aires, Argentina. Pathologic myopia is the leading cause in working age / Análisis de discapacidad visual en Buenos Aires, Argentina. La miopía patológica es la principal causa en edad laboral

Abstract This study assessed the causes of visual impairment over a decade in Buenos Aires City. This is a retrospective case series where we reviewed the database of visual disability certificates issued by the Buenos Aires City Ministry of Health between 2009 and 2017. In Argentina, visual disability is defined as a visual acuity ≤ 20/200 in the better eye, or a corresponding visual field of less than 20 degrees in the less impaired eye. The database included the following variables: year of issue, age, gender, and cause of visual disability. Between 2009 and 2017 a total of 7656 subjects were certified as legally blind. The mean age of the sample was 57 ± 21 years and 52.1% were females. The emission was near 700 certificates per year. The age distribution showed that 62.8% of certificates were from patients older than 50 years and that only 6.6% were given to subjects under 20. The leading causes of visual disability in Buenos Aires City were age-related macular degeneration (ARMD) with a rate of 15.5%, degenerative myopia (14.4%), primary open-angle glaucoma (11.3%) and diabetic retinopathy (6.6%). In subjects younger than 50, degenerative myopia was the first cause of visual disability. Interestingly in Argentina, where the prevalence of myopia is low, degenerative myopia is found to be the major cause of visual disability in middle-aged adult subjects. Population and clinical methods to avoid this preventable disease should need to be implemented as a matter of urgency.

Resumen Este trabajo estudia las causas de la discapacidad visual durante una década en la Ciudad de Buenos Aires. Se presenta una serie de casos retrospectiva donde se revisó la base de datos de certificados de discapacidad visual emitidos por el Ministerio de Salud de la Ciudad de Buenos Aires entre 2009 y 2017. En Argentina, la discapacidad visual se define como una agudeza visual ≤ 20/200 en el mejor ojo, o un campo visual correspondiente de menos de 20 grados en el ojo menos deteriorado. La base de datos incluyó las siguientes variables: año de emisión, edad, sexo y causa de la discapacidad visual. Entre 2009 y 2017 se certificaron un total de 7656 sujetos con ceguera legal. La edad media de la muestra fue de 57 ± 21 años y el 52.1% fueron mujeres. La distribución por edades mostró que el 62.8% de los certificados fueron dados a pacientes mayores de 50 años y que solo el 6.6% se otorgó a menores de 20 años. Las principales causas de discapacidad visual fueron la degeneración macular asociada a la edad (DMAE) (15.5%), la miopía degenerativa (14.4%), el glaucoma primario de ángulo abierto (11.3%) y la retinopatía diabética (6.6%). En los menores de 50 años, la miopía degenerativa fue la primera causa de discapacidad visual. Resulta interesante que, en Argentina, donde la prevalencia de miopía es baja, la miopía degenerativa sea la principal causa de discapacidad visual en adultos de mediana edad.

Lead facilitates foci formation in a Balb/c-3T3 two-step cell transformation model: role of Ape1 function.

Several possible mechanisms have been examined to gain an understanding on the carcinogenic properties of lead, which include among others, mitogenesis, alteration of gene expression, oxidative damage, and inhibition of DNA repair. The aim of the present study was to explore if low concentrations of lead, relevant for human exposure, interfere with Ape1 function, a base excision repair enzyme, and its role in cell transformation in Balb/c-3T3. Lead acetate 5 and 30 µM induced APE1 mRNA and upregulation of protein expression. This increase in mRNA expression is consistent throughout the chronic exposure. Additionally, we also found an impaired function of Ape1 through molecular beacon-based assay. To evaluate the impact of lead on foci formation, a Balb/c-3T3 two-step transformation model was used. Balb/c-3T3 cells were pretreated 1 week with low concentrations of lead before induction of transformation with n-methyl-n-nitrosoguanidine (MNNG) (0.5 µg/mL) and 12-O-tetradecanoylphorbol-13-acetate (TPA) (0.1 µg/mL) (a classical two-step protocol). Morphological cell transformation increased in response to lead pretreatment that was paralleled with an increase in Ape1 mRNA and protein overexpression and an impairment of Ape1 activity and correlating with foci number. In addition, we found that lead pretreatment and MNNG (transformation initiator) increased DNA damage, determined by comet assay. Our data suggest that low lead concentrations (5, 30 µM) could play a facilitating role in cellular transformation, probably through the impaired function of housekeeping genes such as Ape1, leading to DNA damage accumulation and chromosomal instability, one of the most important hallmarks of cancer induced by chronic exposures.

Síndrome Hipereosinofílico con Angioedema Recurrente: reporte de un caso clínico / Recurrent Angioedema with hypereosinophilic syndrome: a case report

El Síndrome Hipereosinofílico (SHE) constituye un grupo heterogéneo de enfermedades, que se caracterizan por una marcada eosinofilia en sangre, mayor a 1500 cel/mm³ de más de seis meses de evolución, asociado a daño de múltiples órganos, por infiltración eosinofílica ó liberación de mediadores. La eosinofilia es un hallazgo común en la práctica clínica, pero cuando se encuentran valores elevados de eosinófilos constituye un desafío diagnóstico. Presentamos el caso clínico de una paciente con antecedente de angioedema facial recurrente que consultó por tos poco productiva, toracodinia y disnea. El laboratorio mostró insuficiencia respiratoria con eosinofilia severa. La radiografía de tórax confirmó infiltrados pulmonares y derrame pleural. La paciente fue sometida a varios estudios complementarios, que nos orientaron hacia el diagnóstico de Síndrome Hipereosinofílico Idiopático, debido a la ausencia de causas secundarias y al hallazgo de eosinófilos en varios tejidos como médula ósea, líquido pleural, y lavado broncoalveolar. Se observó buena respuesta al tratamiento con corticoides sistémicos, logrando remisión completa de la enfermedad.

Hypereosinophilic Syndrome (HES) is a heterogeneous group of diseases, which are characterized by a marked eosinophilia in blood, greater than 1500 cells / mm³ over six months duration, associated with damage to multiple organs, eosinophilic infiltration, or release mediators. Eosinophilia is a common finding in clinical practice, but when levels of eosinophils are elevated can be a diagnostic challenge. We report the case of a patient with a history of recurrent facial angioedema, she consulted for some productive cough, dyspnea and toracodinia. The laboratory showed severe respiratory failure with eosinophilia. Chest radiography confirmed pulmonary infiltrates and pleural effusion. The patient underwent several complementary studies that guided us to the diagnosis of Idiopathic Hypereosinophilic Syndrome due to absence of secondary causes and finding of eosinophils in various tissues such as bone marrow, pleural fluid, and bronchoalveolar lavage. Good response to treatment with systemic corticosteroids was observed, achieving complete remission of the disease.

Coinfección por virus de inmunodeficiencia humana y micobacterias en un hospital universitario de alta complejidad en Colombia / Co-infection with human immunodeficiency virus and mycobacteria in a tertiary referral hospital in Colombia

Antecedentes: La coinfección por virus de inmunodeficiencia humana (VIH) y micobacterias tiene un efecto dual; el riesgo de enfermedad extrapulmonar y diseminada por micobacterias se incrementa y la progresión de la enfermedad VIH se acelera. La tuberculosis (TB) es la entidad que más amenaza la vida en estos pacientes. Metodología: Estudio observacional, descriptivo, retrospectivo. Objetivo: Determinar las características epidemiológicas, clínicas y el perfil de resistencia en los pacientes con coinfección VIH y micobacterias. Resultados: De 159 pacientes con diagnóstico de infección por VIH, 44 (27,7%) tenían coinfección por micobacterias. La edad promedio fue de 36,7 años ± 11,3. El 86% fueron hombres. Al ingreso 66% tenía síndrome de inmunodeficiencia adquirida (SIDA), 20% historia de TB y 11% historia de otras enfermedades de transmisión sexual. El 50% tenía linfocitos T CD4 <50/mm³. Las principales comorbilidades fueron neoplasias hematológicas 11%, insuficiencia cardiaca 4,5% y enfermedad linfoproliferativa 4,5%. La incidencia anual fue de 4,6%. Las formas diseminadas fueron el 54% de los casos. Se identificó M. tuberculosisen 77,3%, micobacterias no tuberculosas (MNT) en 18,3% y en el 4,5% no fue posible establecerla especie. El 2,5% de los aislamientos de M. tuberculosis fueron multifarmacorresistentes (TB-MDR) y en 18,2% se identificó resistencia a un solo fármaco o resistencia combinada. En el 54%de los pacientes se documentó compromiso pulmonar. La letalidad fue del 9,1%. Conclusión: En nuestros pacientes, la infección por M. tuberculosis es la más frecuente y es llamativa la alta prevalencia de resistencia al menos a un fármaco y la TB-MDR. Las infecciones por MNT son cada vez más frecuentes. Las formas diseminadas y extrapulmonares son muy importantes. La incidencia anual es alta.

Background: Co-infection with the human inmunodeficiency virus (HIV) and mycobacteria hasa synergistic effect; the risk of extrapulmonary and disseminated mycobacterium disease isincreased and the progression of HIV disease is accelerated. Tuberculosis (TB) is the entity thatis most life threatening to these patients. Methodology: Observational, descriptive and retrospective study. Objective: To determine the epidemiological and clinical characteristics and the resistanceprofile in patients coinfected with HIV and mycobacteria. Results: Of 159 patients diagnosed with HIV, 44 (27.7%) patients were co-infected with myco-bacteria. The average age was 36.7 years ± 11.3. Some 86% were men. At admission, 66% hadacquired immune deficiency syndrome (AIDS), 20% a history of TB and 11% a history of othersexually transmitted diseases. A total of 50% reported a count of CD4 lymphocytes less than50 cells/mm 3 . Major comorbidities were haematological malignancies in 11%, heart failure in4.5%, and lymphoproliferative disease in 4.5%. The annual incidence was 4.6%. Disseminatedforms were found in 54% of cases. M. tuberculosis was identified in 77.3%, non-tuberculousmycobacteria (NTM) in 18.3% and in 4.5%, it was not possible to establish the species. Some2.5% of isolates of M. tuberculosis were multidrug-resistant (MDR-TB) and 18.2% were resistantto a single drug or had combined resistance. There was documented pulmonary involvement In54% of patients. Mortality was 9.1%. Conclusion: In our patients, infection with M. tuberculosis was the most common and the highprevalence of resistance to at least one drug and MDR-TB was striking. NTM infections are becoming more common. The extra-pulmonary and disseminated forms are common, and annual incidence is high.

Bacterial lipopolysaccharide protects the retina from light-induced damage.

Light-induced damage is a widely used model to study retinal degeneration. We examined whether bacterial lipopolysaccharide (LPS) protects the retina against light-induced injury. One day before intense light exposure for 24 h, rats were intravitreally injected with LPS in one eye and vehicle in the contralateral eye. At several time points after light exposure, rats were subjected to electroretinography and histological analysis. Bax, Bcl-xL, p-Akt, and p-Stat3 levels were assessed by Western blotting, and retinal thiobarbituric acid reactive substances levels were measured as an index of lipid peroxidation. One group of animals received injections of dexamethasone, aminoguanidine (an inducible NOS inhibitor), 5-hydroxydecanoic acid (a mitochondrial K(+) /ATP channel blocker), or wortmannin [a phosphoinositide-3-kinase (PI3K) inhibitor] in order to analyze their effect on the protection induced by LPS. LPS afforded significant morphologic and functional protection in eyes exposed to intense light. Light damage induced an increase in mitochondrial Bax/cytoplasmic Bax ratio, and lipid peroxidation which were prevented by LPS. Dexamethasone and wortmannin (but not aminoguanidine or 5-hydroxydecanoic acid) prevented the effect of LPS. Moreover, wortmannin prevented the effect of LPS on p-Akt levels. These results indicate that LPS provides retinal protection against light-induced stress, probably through a PI3K/Akt-dependent mechanism.

Effect of bacterial lipopolysaccharide on ischemic damage in the rat retina.

PURPOSE: The purpose of this study was to investigate whether bacterial lipopolysaccharide (LPS) induces ischemic preconditioning in the rat retina, and, if so, whether nitric oxide (NO) is involved in this process. METHODS: Rats were intravitreously injected with different doses of LPS (0.1, 1, or 5 microg) in one eye and vehicle in the contralateral eye 24 hours before retinal ischemia induced by increasing intraocular pressure to 120 mm Hg for 40 or 60 minutes. Subsequently, 7 or 14 days after ischemia, the rats were subjected to electroretinography and histologic analysis. One group of animals received intraperitoneal injections of NOS inhibitors, N-nitro-L-arginine methyl ester (L-NAME) aminoguanidine or N-(3-(aminomethyl)benzyl)acetamidine (W1400) before the injection of LPS or vehicle. Retinal nitric oxide synthase (NOS) activity was assessed through the conversion of (3)H-L-arginine to (3)H-L-citrulline. RESULTS: One microgram (but not 0.1 or 5 microg) LPS afforded significant morphologic and functional protection in eyes exposed to ischemia-reperfusion injury. The beneficial effect of LPS was reversed by treatment with L-NAME, aminoguanidine, or W1400. LPS (1 and 5 microg, but not 0.1 microg) significantly increased retinal NOS activity. CONCLUSIONS: These results indicate that LPS provides retinal protection against ischemia-reperfusion injury in a dose-dependent manner, probably through an inducible NOS-dependent mechanism.

'Candidatus Phytoplasma lycopersici', a phytoplasma associated with 'hoja de perejil' disease in Bolivia.

New diseases known locally as 'hoja de perejil' of tomato (Lycopersicon esculentum Mill) and 'brotes grandes' of potato (Solanum tuberosum L.) were first recognized in surveys of production fields in Bolivia during 2000-2003. Alfalfa (Medicago sativa) witches' broom and little leaf diseases of native weeds Morrenia variegata and mora-mora (Serjania perulacea) were also identified near to production fields. Phytoplasma aetiology was attributed to each of these diseases following detection and initial identification of aster yellows group (16SrI) phytoplasmas in all five diseased plant species. While potato, alfalfa and mora-mora plants contained indistinguishable 16SrI-B strains, 'hoja de perejil' (THP) and morrenia little leaf (MVLL)-associated phytoplasma strains shared 97.5 % 16S rRNA gene sequence similarity with 'Candidatus Phytoplasma asteris' and related strains and <95 % similarity with all other 'Candidatus Phytoplasma' species. Phylogenetic analysis of 16S rRNA gene sequences indicated that the THP and MVLL phytoplasmas represent a novel lineage within the aster yellows (16SrI) group and, on the basis of unique 16S rRNA gene sequences, we propose that THP and MVLL phytoplasmas represent 'Candidatus Phytoplasma lycopersici', with THP as the reference strain.