Effects of statin therapy in hospitalized adult COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: COVID-19 is associated with endothelial activation and systemic inflammation; consequently, statins can be used in its treatment as they have anti-inflammatory, antithrombotic, and profibrinolytic properties and may interfere with COVID-19 viral entry into cells through disruption of cell membrane lipid rafts. OBJECTIVE: We performed a meta-analysis of randomized clinical trials that compared statin therapy to placebo or to standard care in adult patients hospitalized for COVID-19. METHODS: We searched the MEDLINE, EMBASE, and Cochrane Library databases for all-cause mortality, hospitalization duration, and admission to the intensive care unit. RESULTS: Of the 228 studies reviewed, four studies were included, with a total of 1,231 patients, of whom 610 (49.5%) were treated with statins. There was no significant difference in all-cause mortality (odds ratio [OR] 0.96; 95% confidence interval [95%CI]: 0.61-1.51; p=0.86; I2=13%), duration of hospitalization (mean difference [MD] 0.21; 95%CI: -1.74-2.16; p=0.83; I2=92%), intensive care unit admission (OR= 3.31; 95%CI: 0.13-87.1; p=0.47; I2=84%), need for mechanical ventilation (OR= 1.03; 95%CI: 0.36-2.94; p=0.95; I2=0%), or increase in liver enzyme levels (OR= 0.58; 95%CI: 0.27-1.25; p=0.16; I2=0%) between patients treated with or without statin therapy. CONCLUSION: Our findings suggest that in adult patients hospitalized with COVID-19, statin therapy results in no difference in clinical outcomes when compared to outcomes by placebo or standard of care. Prospero database registration: (www.crd.york.ac.uk/prospero) under the number CRD42022338283.

Effects of Tezepelumab on Quality of Life of Patients with Moderate-to-Severe, Uncontrolled Asthma: Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: To assess the effects of tezepelumab on quality of life (QoL) in patients with moderate-to-severe, uncontrolled asthma. RECENT FINDINGS: Tezepelumab improves pulmonary function tests (PFTs) and reduces the annualized asthma exacerbation rate (AAER) in patients with moderate-to-severe, uncontrolled asthma. We searched MEDLINE, Embase, and Cochrane Library from inception to September 2022. We included randomized controlled trials comparing tezepelumab versus placebo in patients aged ≥ 12 years with asthma on medium- or high-dose inhaled corticosteroids with ≥ 1 additional controller medication for ≥ 6 months and who had ≥ 1 asthma exacerbation in the 12 months before enrollment. We estimated effects measures with a random-effects model. Of 239 records identified, three studies were included, with a total of 1,484 patients. Tezepelumab significantly decreased biomarkers of T helper 2-driven inflammation, including blood eosinophil count (MD -135.8 [95% CI -164.37, -107.23]) and fractional exhaled nitric oxide (MD -9.64 [95% CI -13.75, -5.53]); improved PFTs, including pre-bronchodilator forced expiratory volume in 1 s (MD 0.18 [95% CI 0.08-0.27]); reduced the AAER (MD 0.47 [95% CI 0.39-0.56]); improved asthma-specific health-related QoL in the Asthma Control Questionnaire-6 (MD -0.33 [95% CI -0.34, -0.32]), Asthma Quality of Life Questionnaire for 12 Years and Older (MD 0.34 [95% CI 0.33, -0.35]), Asthma Symptom Diary (MD -0.11 [95% CI -0.18, -0.04]), and European Quality of Life 5 Dimensions 5 Levels Questionnaire (SMD 3.29 [95% CI 2.03, 4.55]) scores, although not clinically important; and did not change key safety outcomes, including any adverse event (OR 0.78 [95% CI 0.56-1.09]).

Effects of statin therapy in hospitalized adult COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT Introduction COVID-19 is associated with endothelial activation and systemic inflammation; consequently, statins can be used in its treatment as they have anti-inflammatory, antithrombotic, and profibrinolytic properties and may interfere with COVID-19 viral entry into cells through disruption of cell membrane lipid rafts. Objective We performed a meta-analysis of randomized clinical trials that compared statin therapy to placebo or to standard care in adult patients hospitalized for COVID-19. Methods We searched the MEDLINE, EMBASE, and Cochrane Library databases for all-cause mortality, hospitalization duration, and admission to the intensive care unit. Results Of the 228 studies reviewed, four studies were included, with a total of 1,231 patients, of whom 610 (49.5%) were treated with statins. There was no significant difference in all-cause mortality (odds ratio [OR] 0.96; 95% confidence interval [95%CI]: 0.61-1.51; p=0.86; I2=13%), duration of hospitalization (mean difference [MD] 0.21; 95%CI: -1.74-2.16; p=0.83; I2=92%), intensive care unit admission (OR= 3.31; 95%CI: 0.13-87.1; p=0.47; I2=84%), need for mechanical ventilation (OR= 1.03; 95%CI: 0.36-2.94; p=0.95; I2=0%), or increase in liver enzyme levels (OR= 0.58; 95%CI: 0.27-1.25; p=0.16; I2=0%) between patients treated with or without statin therapy. Conclusion Our findings suggest that in adult patients hospitalized with COVID-19, statin therapy results in no difference in clinical outcomes when compared to outcomes by placebo or standard of care. Prospero database registration: (www.crd.york.ac.uk/prospero) under the number CRD42022338283.

miR-197, miR-26a and miR-27a analysis in chronic lymphocytic leukemia.

Aims: Chronic lymphocytic leukemia (CLL) involves the proliferation and increase of B-lymphocytes in the peripheral blood, bone marrow and lymphoid organs. This study evaluated the microRNAs miR-197, miR-26a and miR-27a as potential biomarkers for CLL. Patients & Methods: Eighty-two patients with CLL and 62 control subjects (CT) were investigated for these targets, using quantitative PCR (qPCR). Results: A significant reduction of all microRNAs was observed in CLL compared to the controls (p < 0.001). Significant negative correlations were observed for the clinical staging groups. After adjusting for multiple logistic regression analysis, miR-197 and miR-26a remained as possible independent risk factors related to the CLL. Conclusions: Our data indicated good performance of this microRNAs as potential biomarkers in CLL.

Chronic Lymphocytic Leukemia (CLL): evaluation of AKT protein kinase and microRNA gene expression related to disease pathogenesis

Abstract The present study evaluated 56 patients diagnosed with Chronic Lymphocytic Leukemia (CLL) and a control group of 44 clinically healthy subjects with no previous history of leukemia. Genetic expressions of AKT and microRNAs were evaluated by quantitative PCR (qPCR). A significant increase in AKT gene expression in patients when compared to controls was observed (p = 0.017). When the patients were stratified according to Binet subgroups, a significant difference was observed between the subgroups, with this protein kinase appearing more expressed in the B+C subgroup (p = 0.013). Regarding miRNA expression, miR-let-7b and miR-26a were reduced in CLL patients, when compared to controls. However, no significant differences were observed in these microRNA expressions between the Binet subgroups (A versus B+C). By contrast, miR-21 to miR-27a oncogenes showed no expression difference between CLL patients and controls. AKT protein kinase is involved in the signaling cascade that occurs with BCR receptor activation, leading to increased lymphocyte survival and protection against the induction of cell death in CLL. Thus, increased AKT protein kinase expression and the reduction of miR-let-7b and miR-26a, both tumor suppressors, may explain increased lymphocyte survival in CLL patients and may be promising markers for the prognostic evaluation of this disease.

Biological properties and phytochemical characterization from Miconia chamissois Naudin aqueous extract / Propiedades biológicas y caracterización fitoquímica del extracto acuoso de Miconia chamissois Naudin

The objective of this study was to evaluate biological and phytochemical properties of the aqueous extract from the leaves of Miconia chamissois Naudin (AEMC). Phytochemical properties were assessed by analyzing the chromatographic profile and the polyphenol content of AEMC. Biological properties evaluation was conducted based on cytotoxicity assay and by evaluating the antioxidant, antimicrobial, and enzymatic inhibition activities. Results indicated the presence of phytochemicals in AEMC such as flavonoids and polyphenols, including rutin, isoquercitrin and vitexin derivatives. AEMC showed antioxidant activity, which may be attributed to the high polyphenolic content. Moreover, AEMC demonstrated in vitro enzyme inhibition activity against tyrosinase and alpha-amylase, as well as showed low cytotoxicity. On the other hand, AEMC exhibited weak antimicrobial activity against S. aureusand C. albicans. Thus, AEMC is a promising alternative in search of potential drugs for the treatment of diseases induced by oxidative stress and inflammation, conditions due to hyperpigmentation processes, such as melisma, as well as for diabetes.

El objetivo de este estudio fue detectar las propiedades biológicas y fitoquímicos del extracto acuoso de las hojas de Miconia chamissois Naudin (AEMC). Las propiedades fitoquímicas se evaluaron analizando el perfil cromatográfico y el contenido de polifenoles de AEMC. La evaluación de las propiedades biológicas se realizó en base al ensayo de citotoxicidad y evaluando las actividades de inhibición antioxidante, antimicrobiana y enzimática. Los resultados indicaron la presencia de fitoquímicos en AEMC, como flavonoides y polifenoles, que incluyen derivados de rutina, isoquercitrina y vitexina. AEMC mostró una actividad antioxidante considerable, que puede atribuirse al alto contenido polifenólico. Además, AEMC exhibió actividad de inhibición enzimática in vitro contra tirosinasa y alfa-amilasa, así como mostró baja citotoxicidad. Por otro lado, AEMC demostró actividad antimicrobiana débil contra S. aureusy C. albicans. Por lo tanto, AEMC es una alternativa prometedora en busca de posibles drogas para el tratamiento de enfermedades inducidas por el estrés oxidativo y la inflamación, afecciones debidas a procesos de hiperpigmentación, como el melasma, así como para la diabetes.

Assessment of the cytoprotective effect of the homeopathic compound Canova® on African green monkey kidney (VERO) cell line exposed to the drug dipyrone sodium.

Dipyrone or metamizole is one of the most frequently used analgesic worldwide. Despite its widespread use, this drug may exert genotoxic and cytotoxic effects on lymphocytes. Therefore, studies with therapeutic agents that may provide protection against these effects are important. The homeopathic compound Canova® (CA) appears to be a beneficial candidate for preventing DNA damage and cellular lethality, since this compound acts as an immunomodulator associated with cytoprotective actions. Hence, the aim of the present investigation was to determine the potential cytoprotective effects of CA using cell line VERO as a model. VERO cells were incubated with sodium dipyrone and subsequently subject to the comet, apoptosis and immunocytochemistry assays. Data demonstrated that sodium dipyrone induced an increase in DNA damage index (DI) employing the comet assay. However, when VERO cells were co-treated with CA at the three concentrations studied, a significant reduction in DI was observed, indicating an antigenotoxic effect attributed to CA. Further dipyrone induced an elevation in %apoptosis at 24 and 48 hr. However, when dipyrone was co-incubated with CA, a significant reduction in %apoptosis was noted at the three concentrations of CA employed. Results from immunocytochemical analysis showed a rise in the expression of caspase 8 and cytochrome C when cells were exposed to dipyrone. In contrast, co-treatment of dipyrone and CA significantly reduced the effect of dipyrone. Therefore, evidence indicated that CA acted as an anticytotoxic and antigenotoxic agent counteracting damage induced by dipyrone.

Genotoxic and cytotoxic effects of the drug dipyrone sodium in African green monkey kidney (Vero) cell line exposed in vitro.

Dipyrone or metamizole is one of the most used analgesics, mainly due to its low financial cost. However, in some countries, the sale of dipyrone is prohibited due to reported severe cases of agranulocytosis as a result of its use. Despite its high use, studies showing genotoxic and cytotoxic effects of dipyrone in mammalian cells are scarce. Therefore, in the present study, we assessed cell viability, genotoxic effects, cytotoxic effects (by apoptosis and necrosis induction), and the induction of reactive oxygen species (ROS) in Vero cells (a cell line obtained from the red kidney of green monkey) exposed to dipyrone. Our results showed a significant reduction in viability of cells exposed to dipyrone by the MTT assay. A significant increase in damage index evaluated by a comet assay was also observed, which indicates its genotoxic effects. In which concerns the cytotoxic effects of dipyrone, we observed a significant increase in the number of apoptotic cells using fluorescent dyes after 24 h and 48 h of treatment with the drug. Our results also showed that there was no significant difference in the induction of ROS generation after treatment of the cells with the drug assessed by the DCFH-DA assay. Thus, our work showed that dipyrone is both a genotoxic and cytotoxic drug to Vero cells in the assessed conditions.

Draft genome sequence of Wickerhamomyces anomalus LBCM1105, isolated from cachaça fermentation.

Wickerhamomyces anomalus LBCM1105 is a yeast isolated from cachaça distillery fermentation vats, notable for exceptional glycerol consumption ability. We report its draft genome with 20.5x in-depth coverage and around 90% extension and completeness. It harbors the sequences of proteins involved in glycerol transport and metabolism.

High-affinity transport, cyanide-resistant respiration, and ethanol production under aerobiosis underlying efficient high glycerol consumption by Wickerhamomyces anomalus.

Wickerhamomyces anomalus strain LBCM1105 was originally isolated from the wort of cachaça (the Brazilian fermented sugarcane juice-derived Brazilian spirit) and has been shown to grow exceptionally well at high amounts of glycerol. This paramount residue from the biodiesel industry is a promising cheap carbon source for yeast biotechnology. The assessment of the physiological traits underlying the W. anomalus glycerol consumption ability in opposition to Saccharomyces cerevisiae is presented. A new WaStl1 concentrative glycerol-H+ symporter with twice the affinity of S. cerevisiae was identified. As in this yeast, WaSTL1 is repressed by glucose and derepressed/induced by glycerol but much more highly expressed. Moreover, LBCM1105 aerobically growing on glycerol was found to produce ethanol, providing a redox escape to compensate the redox imbalance at the level of cyanide-resistant respiration (CRR) and glycerol 3P shuttle. This work is critical for understanding the utilization of glycerol by non-Saccharomyces yeasts being indispensable to consider their industrial application feeding on biodiesel residue.

In vitro assessment of cytotoxic, genotoxic and mutagenic effects of antimalarial drugs artemisinin and artemether in human lymphocytes.

Artemisinin is a substance extracted from the Chinese plant Artemisia annua L. widely used in natural medicine for the treatment of various diseases. Artemether is a substance synthesized from artemisinin, and both drugs are commonly administered in the treatment of malaria. Although considered effective antimalarial drugs, very little is known about the genotoxic, cytotoxic and mutagenic effects of these drugs. Therefore, in the present study, we evaluated the genotoxic, mutagenic and cytotoxic effects of artemisinin (12.5, 25 and 50 µg/mL) and artemether (7.46; 14.92 and 29.84 µg/mL) in cultured human lymphocytes using the comet assay, the micronucleus test and the cytotoxicity assay for detection of necrosis and apoptosis by acridine orange/ethidium bromide staining. Our results showed a significant increase (p < 0.05) in the rate of DNA damage measured by comet assay and in the micronucleus frequency after treatment with both drugs. It was also observed that only artemisinin induced a statistically significant increase (p < 0.05) in the number of lymphocytes with death by necrosis 48 h after treatment. The results demonstrated that these two drugs induce mutagenic, genotoxic and cytotoxic effects in cultured human lymphocytes. Our data indicate the need for caution in the use of such drugs, since genotoxic/mutagenic effects may increase the risk of carcinogenesis.

Grupo operativo com primigestas: uma estratégia de promoção à saúde / Operative group of primigravidae: a health promotion strategy / Grupo operante con primigestas: una estrategia de promoción de la salud

Objetivo: Promover ações de educação em saúde por meio de grupo operativo com primigestas acompanhadas pela Estratégia Saúde da Família. Métodos: Pesquisa-ação com abordagem qualitativa, realizada no segundo trimestre de 2013. A coleta de informações ocorreu por meio de grupo operativo com dez primigestas, tendo como cenário a Unidade Básica de Saúde localizada na porção sul do município de Sobral, Ceará, Brasil. A análise temática foi adotada como técnica de análise de dados. Resultados: A ação do grupo operativo com as primigestas possibilitou a explicitação de variáveis relacionadas: ao medo do parto; à ansiedade diante da sensação de tornar-se mãe, identificada pelas necessidades de aprendizagem; à emissão de aspectos sinalizadores que permitiram a identificação de papéis assumidos no âmbito grupal e à compreensão desse espaço para a promoção da saúde. Evidenciou-se a importância da utilização de uma abordagem diferenciada no complemento às consultas de pré-natal, em que se associa a teoria com a prática. Conclusão: O grupo operativo se revelou como estratégia pedagógica e educativa a ser utilizada junto às primigestas na Estratégia Saúde da Família, no sentido da promoção à saúde. O espaço grupal possibilitou a explicitação de ansiedades/medos inerentes à primeira gestação e a oportunidade de uma construção de conhecimento coletivo.

Objective: To promote health education activities in an operative group of primigravidae served by the Family Health Strategy. Methods: Qualitative action research carried out in the second quarter of 2013. Data were collected from an operative group of 10 primigravidae at a Primary Health Care center located in the south of the municipality of Sobral, Ceará, Brazil. Thematic analysis was adopted as the data analysis technique. Results: The group of primigravidae highlighted several variables: fear of delivery; anxiety surrounding motherhood, which was identified through their learning needs; aspects that allowed the identification of the roles taken within the group; and the understanding of this space for health promotion. It is evident the importance of using a differentiated approach in addition to prenatal consultations by combining theory and practice. Conclusion: The operative group proved to be an educational and pedagogical tool that should be used in primigravidae served by the Family Health Strategy to promote their health. The group allowed to highlight anxieties/fears inherent to the first pregnancy and the opportunity to build collective knowledge.

Objetivo: Promover acciones de educación en salud a través de un grupo operante de primigestas asistidas por la Estrategia Salud de la Familia. Métodos: Investigación-acción de abordaje cualitativo realizada en el segundo trimestre de 2013. La recogida de las informaciones se dio a través de un grupo operante con diez primigestas en el escenario de la Unidad Básica de Salud localizada en la zona sur del municipio de Sobral, Ceará, Brasil. El análisis temático ha sido adoptado como la técnica para el análisis de los datos. Resultados: El abordaje de grupo operante con las primigestas ha posibilitado la evidencia de variables relacionadas al miedo del parto; la ansiedad delante la sensación de tornarse madre identificada por las necesidades de aprendizaje; a la emisión de aspectos que permitieron la identificación de papeles asumidos en al ámbito del grupo y la comprensión de ese espacio para la promoción de la salud. Se evidenció la importancia de la utilización de un abordaje diferenciado para el complemento de las consultas prenatal en el cual se asocia la teoría con la práctica. Conclusión: El grupo operante se ha revelado como estrategia pedagógica y educativa para ser utilizada con las primigestas de la Estrategia Salud de la Familia para la promoción de la salud. El espacio del grupo ha posibilitado la evidencia de ansiedades/miedos inherentes al primer embarazo y la oportunidad de una construcción del conocimiento colectivo.

Advances in chronic lymphocytic leukemia pharmacotherapy.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease that affects B lymphocytes in most cases. Leukemic lymphocytes have prolonged longevity, defined by resistance to apoptosis. These cells can accumulate in peripheral blood, bone marrow, and solid lymphoid organs. CLL may be indolent or aggressive and has a range of prognostic factors such as expression of CD38 and ZAP-70, immunophenotypic and cytogenetic changes, imbalanced apoptosis proteins, and others. Although CLL has a low mortality rate, this disease is generally not considered curable until today. CLL treatment involves alkylating agents and glucocorticoids, purine analogs, monoclonal antibody therapies, and bone marrow transplantation. In recent decades, new drugs have appeared focusing on new targets and specific molecules, such as the BCR receptor, Bruton's tyrosine kinase, phosphatidylinositol 3-kinase, spleen tyrosine kinase, apoptosis proteins and microRNAs. The most appropriate treatment for CLL is one that involves in its protocol a combination of drugs according to the prognostic factors presented by each patient. In this sense, treatment individualization is essential. This article examines standard treatments for CLL and explores new treatments and potential new targets, as well as schematic protocols to understand where we are, how the treatment has evolved, and the advantages and disadvantages of new targets for CLL therapy.

Paciente com proptose ocular associado a mucocele etmoidal: apresentação clínica e tratamento / Patient with ocular properties associated with ethmoidal mucocele: clinical presentation and treatment

Resumo Relato de um caso clínico de proptose ocular relacionado com mucocele etmoidal, o caso é raro e seu acometimento ocular não é comumente relacionado na literatura. Ressaltamos ainda sua apresentação clínica e o tratamento instituído. W.L.S, Paciente do sexo masculino, 27 anos procedente de Fortaleza-CE. Comparece ao ambulatório HUWC com queixa de baixa da acuidade visual percebida há 10 dias em olho direito (OD). Ao exame oftalmológico melhor acuidade visual corrigida de 20/200 OD e 20/20 olho esquerdo (OE), ausência de abdução e elevação do OD com ptose leve (distância margem reflexo 1-2 mm) e diplopia ao olhar para direita. Proptose OD de aspecto axial de grau moderado (24mm). Biomicroscopia lâmpada de fenda sem alterações. Pressão intraocular: 18mmHg OD 12 mmHg OE. Fundo de olho: OD aspecto palidez discreta de disco, sem outras alterações e OE dentro da normalidade. Solicitada tomografia de crânio (TC) que demonstrou presença de lesão arredondada em área do seio etmoidal penetrando parede óssea da órbita do OD sugestiva de mucocele etmoidal. Encaminhado para serviço de otorrinolaringologia do HUWC, sendo submetido a procedimento cirúrgico endoscópico etmoidectomia. Um mês após o procedimento cirúrgico a acuidade visual OD 20/25, movimentos oculares presentes e simétricos, ausência de diplopia e persistência de leve palidez em OD. Expansão da mucocele pode ocorrer ao longo de muitos anos ou rapidamente. Acometimento ocular com baixa da acuidade visual é incomum como primeiro sintoma, quando ocorre merece tratamento imediato. O tratamento cirúrgico é geralmente indicado no caso e deve ser instituído assim que possível para adequada recuperação visual.

Abstract Report of a clinical case of ocular proptosis related to ethmoidal mucocele, the case is rare and ocular involvement is not commonly related in the literature. We also emphasize its clinical presentation and the treatment instituted. W.L.S., male, 27 years old from Fortaleza-CE. He presents to the HUWC outpatient clinic complaining of low visual acuity perceived for 10 days in the right eye (OD). The ophthalmologic exam showed a best corrected visual acuity of 20/200 OD and 20/20 left eye (OS), absence of abduction and elevation of OD with light ptosis (distance margin 1 - 2 mm) and diplopia when looking to the right. Proptose OD of moderate aspect axial aspect (24mm). Biomicroscopy slit lamp without changes. Intraocular pressure: 18mmHg OD 12 mmHg OS. Background of eye: OD discrete pallor disk appearance, no other changes and OS within normality. A CT scan was performed that showed presence of a rounded lesion in the ethmoidal sinus area penetrating the bone wall of the OD orbit suggestive of ethmoidal mucocele. Forwarded to the otorhinolaryngology service of the HUWC, being submitted to endoscopic surgical procedure etmoidectomy. One month after the surgical procedure visual acuity of OD 20/25, present and symmetrical ocular movements, absence of diplopia and persistence of mild pallor in OD. Expansion of mucocele may occur over many years or rapidly. Ocular involvement with low visual acuity is uncommon as the first symptom, when it occurs it deserves immediate treatment. Surgical treatment is generally indicated in the case and should be instituted as soon as possible for adequate visual recovery.

Evaluation of MiR-15a and MiR-16-1 as prognostic biomarkers in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a B lineage neoplasm, characterized by the accumulation of B lymphocytes of great longevity, and usually develops as a result of the inhibition of apoptosis. Clinical evolution is extremely variable amongst affected individuals with survival ranging from a few months in aggressive cases, to a few decades in cases of indolent CLL. The identification of new prognostic factors, apart from clinical staging, has been an important research topic aiming at a better understanding of CLL. There are approximately one thousand miRNAs in the human genome. They are expressed in specific tissues and changes in this expression are associated with different pathologies. In recent years, several studies have focused on the role of regulatory miRNAs in the pathogenesis of various diseases, including CLL. It has become evident that the profiles of miRNAs have great potential for application in the evaluation of CLL prognosis, since changes in miRNA expression profiles contribute to cell survival, proliferation and development of the disease. The deletion 13q14, the most prevalent alteration in CLL, leads to the deletion of the human tumor suppressor genes miR-15a and miR-16-1, which act on cell proliferation and in the process of apoptosis. Therefore, in patients with 13q deletion, loss of miR-15a and miR-16-1 displaces the expression balance for higher levels of Bcl-2 anti-apoptotic and pro-apoptotic p53 proteins. Regarding these microRNAs, the correlation of miR-15a and miR-16-1 with low-risk CLL is of particular interest. In this context, this mini review summarizes the current evidences on the role of regulatory miRNAs in the pathogenesis of CLL, particularly miR-15a and miR-16-1, involved on cell proliferation and apoptosis. In addition, it is our intention to highlight the potential role of micro RNAs as a marker of prognosis in this disease and to arouse interest in future studies addressing this interesting issue. Several current and future studies may shed light on the role of microRNAs in the pathogenesis of CLL, possibly leading to the development of new laboratory biomarkers.

Prognosis biomarkers evaluation in chronic lymphocytic leukemia.

OBJECTIVE/BACKGROUND: From clinical and biological points of view, chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by a progressive accumulation of lymphocytes in the peripheral blood, bone marrow, and lymphoid organs. New prognostic markers in CLL may be useful to clinicians for predicting outcome and in clinical decision-making. The aim of this study was to evaluate the potential prognostic value of the apoptotic/survival-controlling proteins and protein tyrosine kinase ZAP-70 gene expression in CLL patients and control individuals, correlating such findings with patients' clinical data. METHODS: Fifty-three patients diagnosed with CLL attending the hematology service of a clinical hospital, and 24 healthy individuals with no history of leukemia (Control group) were enrolled in this study. Analyses of apoptotic/survival-controlling proteins were performed by western blot and ZAP-70 gene expression was evaluated by real-time polymerase chain reaction. RESULTS: Significant differences were observed for the p-p38, Mcl-1 long, and Mcl-1 short proteins when patients were compared with CLL and controls. A positive correlation between the results for Mcl-1 short and Mcl-1 long and lymphocyte count was observed, corroborating the hypothesis of an imbalance between proteins of cell survival pathways/apoptosis in CLL. CONCLUSION: ZAP-70 gene expression was not detected as a discriminant biomarker in these CLL patients. An imbalance between apoptosis-related proteins was observed in the present study, corroborating the hypothesis of increased survival of lymphocytes in CLL patients.

In vitro assessment of anticytotoxic and antigenotoxic effects of CANOVA(®).

BACKGROUND: CANOVA(®) (CA) is a homeopathic immunomodulator. It contains several homeopathic medicines prepares according to the Brazilian Pharmacopoeia. CA is indicated in clinical conditions in which the immune system is impaired and against tumors. N-methyl-N-nitrosourea (NMU) is an N-nitroso compound, with genotoxic/mutagenic properties. Although several studies have shown promising results in the use of CA, there are no studies reporting possible antigenotoxic effects. METHOD: This study evaluated the in vitro antigenotoxic and anticytotoxic effects of CA in human lymphocytes exposed to NMU. Samples of human lymphocytes that were subjected to different concentrations of a mixture containing CA and NMU were used. The genotoxicity/antigenotoxicity of CA was evaluated by the comet assay, anticytotoxicity was assessed by quantification of apoptosis and necrosis using acridine orange/ethidium bromide. RESULTS: CA significantly reduced DNA damage induced by NMU and reduced significantly the frequency of NMU-induced apoptosis after 24 h of treatment. CONCLUSION: CA has an important cytoprotective effect significantly reducing the DNA damage and apoptosis induced by the carcinogen NMU.

Branch retinal artery occlusion in Susac's syndrome

Susac's syndrome is a rare disease attribuited to a microangiopathy involving the arterioles of the cochlea, retina and brain. Encefalopathy, hearing loss, and visual deficits are the hallmarks of the disease. Visual loss is due to multiple, recurrent branch arterial retinal occlusions. We report a case of a 20-year-old women with Susac syndrome presented with peripheral vestibular syndrome, hearing loss, ataxia, vertigo, and vision loss due occlusion of the retinal branch artery.

Síndrome de Susac é uma microangiopatia rara que afeta as arteríolas da cóclea, retina e encéfalo. Encefalopatia, perda auditiva e baixa da acuidade visual formam a tríade clássica da doença. A baixa de acuidade visual ocorre devido a múltiplas e recorrentes oclusões de ramo arterial da retina. Relatamos o caso de uma paciente de 20 anos com síndrome de Susac apresentando síndrome vestibular periférica, perda auditiva, vertigem, ataxia e baixa da acuidade visual por oclusão de ramo arterial de retina.

Choroidal metastasis as the first sign of bronchioloalveolar lung cancer: case report.

Metastatic tumors are the most common intraocular malignances and choroid is by far the most common site. Breast and lung cancer are the first cause in women and men respectively. We report the case of a 71-year old woman who had choroidal tumor in her left eye. Further image body scans demonstrated several lesions in both sides of the lungs with dissemination to other organs. Diagnosis of a brochioloalveolar carcinoma established after a biopsy carried out. The patient died before initiating a proper treatment.

Choroidal metastasis as the first sign of bronchioloalveolar lung cancer: case report / Metástase coroidal como primeira manifestação de carcinoma bronquioloalveolar: relato de caso

Metastatic tumors are the most common intraocular malignances and choroid is by far the most common site. Breast and lung cancer are the first cause in women and men respectively. We report the case of a 71-year old woman who had choroidal tumor in her left eye. Further image body scans demonstrated several lesions in both sides of the lungs with dissemination to other organs. Diagnosis of a brochioloalveolar carcinoma established after a biopsy carried out. The patient died before initiating a proper treatment.

Tumor metastático é a neoplasia ocular mais frequente, e a coroide é o local mais comum desta. Tumor de mama seguido de tumor pulmonar são as causas mais comuns de metástases oculares em mulheres e homens, respectivamente. Relatamos o caso de uma paciente de 71 anos com tumor coroidal no olho esquerdo. Posteriormente, estudos de imagem mostraram lesões pulmonares em ambos os pulmões e disseminação a outros órgãos. O diagnóstico de carcinoma bronquioloalveolar foi feito por biópsia. A paciente foi a óbito antes de se iniciar tratamento adequado.