4-Nitrochalcone as a potential drug in non-clinical breast cancer studies.

Breast cancer is a high-magnitude public health problem, continually challenging physicians and scientists worldwide in the field of drug therapy. 4-nitrochalcone (4NC) is a phenolic compound that has promising antitumor activity in vitro, but its application in breast cancer treatment is still poorly explored. This study aimed to evaluate the action of 4NC in vitro and in vivo breast cancer models. The cytotoxic potential of 4NC was tested towards MCF-7 and MDA-MD-231 breast cancer cells, with a lower impact in the non-tumor lineage HB4a. For in vivo studies, solid Ehrlich carcinoma (SEC) was used, a syngeneic mouse model with non-nuclear estrogen and progesterone positivity, characterized by immunohistochemistry. Daily oral administration of 4NC (25 mg kg-1) for 21 days led to a consistent reduction in tumor growth compared to the vehicle group. No signs of toxicity evaluated by hematological, biochemical, histological, and oxidative stress parameters were observed in mice, and the DL50 was >2000 mg kg-1. The effectors Raptor and S6K1 showed decreased activation, with a consequent reduction in protein synthesis; concomitantly, there was an increase in LC3-II levels, but the protective autophagic response was not completed, with the maintenance of p62 levels and cell death. These results open new possibilities for the use of 4NC as a tumor cell metabolism modulating agent.

Molecular BCR::ABL1 Quantification and ABL1 Mutation Detection as Essential Tools for the Clinical Management of Chronic Myeloid Leukemia Patients: Results from a Brazilian Single-Center Study.

Chronic myeloid leukemia (CML) is a well-characterized oncological disease in which virtually all patients possess a translocation (9;22) that generates the tyrosine kinase BCR::ABL1 protein. This translocation represents one of the milestones in molecular oncology in terms of both diagnostic and prognostic evaluations. The molecular detection of the BCR::ABL1 transcription is a required factor for CML diagnosis, and its molecular quantification is essential for assessing treatment options and clinical approaches. In the CML molecular context, point mutations on the ABL1 gene are also a challenge for clinical guidelines because several mutations are responsible for tyrosine kinase inhibitor resistance, indicating that a change may be necessary in the treatment protocol. So far, the European LeukemiaNet and the National Comprehensive Cancer Network (NCCN) have presented international guidelines on CML molecular approaches, especially those related to BCR::ABL1 expression. In this study, we show almost three years' worth of data regarding the clinical treatment of CML patients at the Erasto Gaertner Hospital, Curitiba, Brazil. These data primarily comprise 155 patients and 532 clinical samples. BCR::ABL1 quantification by a duplex-one-step RT-qPCR and ABL1 mutations detection were conducted. Furthermore, digital PCR for both BCR::ABL1 expression and ABL1 mutations were conducted in a sub-cohort. This manuscript describes and discusses the clinical importance and relevance of molecular biology testing in Brazilian CML patients, demonstrating its cost-effectiveness.

Hilab System Device in an Oncological Hospital: A New Clinical Approach for Point of Care CBC Test, Supported by the Internet of Things and Machine Learning.

The complete blood count (CBC) is a highly requested test that is generally restricted to centralized laboratories, which are limited by high cost, being maintenance-demanding, and requiring costly equipment. The Hilab System (HS) is a small, handheld hematological platform that uses microscopy and chromatography techniques, combined with machine learning (ML) and artificial intelligence (AI), to perform a CBC test. This platform uses ML and AI techniques to add higher accuracy and reliability to the results besides allowing for faster reporting. For clinical and flagging capability evaluation of the handheld device, the study analyzed 550 blood samples of patients from a reference institution for oncological diseases. The clinical analysis encompassed the data comparison between the Hilab System and a conventional hematological analyzer (Sysmex XE-2100) for all CBC analytes. The flagging capability study compared the microscopic findings from the Hilab System and the standard blood smear evaluation method. The study also assessed the sample collection source (venous or capillary) influences. The Pearson correlation, Student t-test, Bland-Altman, and Passing-Bablok plot of analytes were calculated and are shown. Data from both methodologies were similar (p > 0.05; r ≥ 0.9 for most parameters) for all CBC analytes and flagging parameters. Venous and capillary samples did not differ statistically (p > 0.05). The study indicates that the Hilab System provides humanized blood collection associated with fast and accurate data, essential features for patient wellbeing and quick physician decision making.

Effectiveness of the polyphenols-rich Sedum dendroideum infusion on gastric ulcer healing in rats: Roles of protective endogenous factors and antioxidant and anti-inflammatory mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Peptic ulcer is an inflammatory disease that therapeutic options are mainly focused in antisecretory drugs. Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is employed in folk medicine for the treatment of gastric ulcers. Recently, our group demonstrated that Sedum dendroideum infusion (SDI) is rich in polyphenols (flavonol glycosides, myricetin, quercetin and kaempferol) and promoted gastroprotection against acute ulcer models, without changes gastric acid secretion. AIM OF THE STUDY: Here, we follow the investigation of the healing effects of SDI (ED50 = 191 mg/kg) in the chronic gastric ulcer model induced by 80% acetic acid in rats, elucidating underlying mechanisms. MATERIAL AND METHODS: Rats were orally treated with vehicle (water, 1 mL/kg), SDI (191 mg/kg), omeprazole (40 mg/kg) or sucralfate (100 mg/kg) twice daily for 5 days after ulcer induction. Following treatments, toxicological effects, macroscopic ulcer appearance, microscopic histological (HE, mucin PAS-staining) and immunohistochemical (PCNA and HSP70) analysis, inflammatory (MPO and NAG activity, cytokine levels measurements) and antioxidant (SOD and CAT) parameters were investigated in gastric ulcer tissues. RESULTS: Oral treatment with SDI accelerated gastric ulcer healing, maintained mucin content and promoted epithelial cell proliferation. SDI also reduced neutrophil and mononuclear leukocyte infiltration, TNF-α and IL-1ß levels and the oxidative stress, restoring SOD and CAT activities in the ulcer tissue. CONCLUSIONS: The gastric healing effect of SDI was mediated through endogenous protective events as well as due to the anti-inflammatory and antioxidant actions. Our observations support and reinforce the traditional utilize of Sedum dendroideum as a natural nontoxic therapeutic alternative for the treatment of gastric ulcers.

Bixin attenuates mechanical allodynia, anxious and depressive-like behaviors associated with experimental diabetes counteracting oxidative stress and glycated hemoglobin.

Neuropathic pain, depression, and anxiety are common comorbidities in diabetic patients, whose pathophysiology involves hyperglycemia-induced increased oxidative stress. Bixin (BIX), an apocarotenoid extracted from the seeds of Bixa orellana, has been used in traditional medicine to treat diabetes and has been recognized by its antioxidant profile. We aimed to investigate the effect of the BIX over the mechanical allodynia, depressive, and anxious-like behaviors associated with experimental diabetes, along with its involved mechanisms. Streptozotocin-induced diabetic rats were treated for 17 days (starting 14 days after diabetes induction) with the corresponding vehicle, BIX (10, 30 or 90 mg/kg; p.o), or INS (6 IU; s.c.). Mechanical allodynia, depressive, and anxious-like behavior were assessed by electronic Von Frey, forced swimming, and elevated plus-maze tests, respectively. Locomotor activity was assessed by the open field test. Blood glycated hemoglobin (HbA1) and the levels of lipid peroxidation (LPO) and reduced glutathione (GSH) were evaluated on the hippocampus, pre-frontal cortex, lumbar spinal cord, and sciatic nerve. Diabetic animals developed mechanical allodynia, depressive and anxious-like behavior, increased plasma HbA1, increased LPO, and decreased GSH levels in tissues analyzed. Repeated BIX-treatment (at all tested doses) significantly attenuated mechanical allodynia, the depressive (30 and 90 mg/kg) and, anxious-like behaviors (all doses) in diabetic rats, without changing the locomotor performance. BIX (at all tested doses) restored the oxidative parameters in tissues analyzed and reduced the plasma HbA1. Thereby, bixin may represent an alternative for the treatment of comorbidities associated with diabetes, counteracting oxidative stress and plasma HbA1.

Aspectos clínicos, laboratoriais e tratamento da leucemia mieloide crônica em cão: relato de caso / Clinical aspects, hematological changes and treatments of chronic myeloid leukemia in dog: case report

O objetivo deste relato é apresentar o caso clínico de uma cadela, sem raça definida, com cinco anos de idade, diagnosticada com leucemia mieloide crônica (LMC). As leucemias são neoplasias malignas que se originam de células precursoras da medula óssea e as consequências podem ser trombocitopenia, anemia, leucocitose persistente e presença de células neoplásicas no sangue. O tratamento de escolha envolve o uso de inibidores de tirosina quinase, porém este não pode ser usado neste caso. Dessa forma a cadela recebeu diferentes protocolos quimioterápicos que incluíram inicialmente hidroxiureia, citarabina, doxorrubicina e prednisona. Devido a remissão parcial dos sinais clínicos e a resposta terapêutica pouco duradoura a essas medicações o protocolo foi alterado para quimioterapia metronômica com clorambucil. O uso desses quimioterápicos não foram eficazes em reduzir a leucocitose e controlar a anemia e trombocitopenia da paciente, devido a ocorrência do surgimento de células imaturas no sangue e resistência aos quimioterápicos. Na ausência da crise e da possibilidade do uso dos inibidores de tirosina quinase, a hidroxiureia permanece sendo o quimioterápico de eleição. O animal apresentou sobrevida de 210 dias, devido a leucocitose e anemia severas pouco responsivas ao protocolo terapêutico utilizado e o surgimento no hemograma de precursores neutrofilicos que ocorreu 46 dias após ao início do tratamento com hidroxiureia.

The aim of this report is to present the clinical case of a five-year-old mixed breed female dog diagnosed with chronic myeloid leukemia (CML). Leukemias are malignant neoplasms that originate from bone marrow precursor cells and the consequences can be thrombocytopenia, anemia, persistent leukocytosis and the presence of neoplastic cells in the blood. The treatment of choice involves the use of tyrosine kinase inhibitors, but it cannot be used in this case. Thus, the dog received different chemotherapy protocols that initially included hydroxyurea, cytarabine, doxorubicin and prednisone. Due to the partial remission of clinical signs and the short-term therapeutic response to these medications, the protocol was changed to metronomic chemotherapy with chlorambucil. The use of these chemotherapeutic agents was not effective in reducing leukocytosis and controlling the patient's anemia and thrombocytopenia, due to the occurrence of immature cells in the blood and resistance to chemotherapeutic agents. In the absence of the crisis and the possibility of using tyrosine kinase inhibitors, hydroxyurea remains the chemotherapy of choice. The animal had a 210-day survival, due to severe leukocytosis and anemia, which were not responsive to the therapeutic protocol used and the appearance in the blood count of neutrophilic precursors that occurred 46 days after the beginning of hydroxyurea treatment.

Aspectos clínicos, laboratoriais e tratamento da leucemia mieloide crônica em cão relato de caso / Clinical aspects, hematological changes and treatments of chronic myeloid leukemia in dog: case report

O objetivo deste relato é apresentar o caso clínico de uma cadela, sem raça definida, com cinco anos de idade, diagnosticada com leucemia mieloide crônica (LMC). As leucemias são neoplasias malignas que se originam de células precursoras da medula óssea e as consequências podem ser trombocitopenia, anemia, leucocitose persistente e presença de células neoplásicas no sangue. O tratamento de escolha envolve o uso de inibidores de tirosina quinase, porém este não pode ser usado neste caso. Dessa forma a cadela recebeu diferentes protocolos quimioterápicos que incluíram inicialmente hidroxiureia, citarabina, doxorrubicina e prednisona. Devido a remissão parcial dos sinais clínicos e a resposta terapêutica pouco duradoura a essas medicações o protocolo foi alterado para quimioterapia metronômica com clorambucil. O uso desses quimioterápicos não foram eficazes em reduzir a leucocitose e controlar a anemia e trombocitopenia da paciente, devido a ocorrência do surgimento de células imaturas no sangue e resistência aos quimioterápicos. Na ausência da crise e da possibilidade do uso dos inibidores de tirosina quinase, a hidroxiureia permanece sendo o quimioterápico de eleição. O animal apresentou sobrevida de 210 dias, devido a leucocitose e anemia severas pouco responsivas ao protocolo terapêutico utilizado e o surgimento no hemograma de precursores neutrofilicos que ocorreu 46 dias

The aim of this report is to present the clinical case of a five-year-old mixed breed female dog diagnosed with chronic myeloid leukemia (CML). Leukemias are malignant neoplasms that originate from bone marrow precursor cells and the consequences can be thrombocytopenia, anemia, persistent leukocytosis and the presence of neoplastic cells in the blood. The treatment of choice involves the use of tyrosine kinase inhibitors, but it cannot be used in this case. Thus, the dog received different chemotherapy protocols that initially included hydroxyurea, cytarabine, doxorubicin and prednisone. Due to the partial remission of clinical signs and the short-term therapeutic response to these medications, the protocol was changed to metronomic chemotherapy with chlorambucil. The use of these chemotherapeutic agents was not effective in reducing leukocytosis and controlling the patient’s anemia and thrombocytopenia, due to the occurrence of immature cells in the blood and resistance to chemotherapeutic agents. In the absence of the crisis and the possibility of using tyrosine kinase inhibitors, hydroxyurea remains the chemotherapy of choice. The animal had a 210-day survival, due to severe leukocytosis and anemia, which were not responsive to the therapeutic protocol used and the appearance in the blood count of neutrophilic precursors that occurred 46 days after the beginning of hydroxyurea treatment.

Salvia lachnostachys Benth has antitumor and chemopreventive effects against solid Ehrlich carcinoma.

Salvia lachnostachys is an herbaceous plant with anti-inflammatory, analgesic and cytotoxic properties. This study investigated the antitumor effect of an ethanolic extract of Salvia lachnostachys leaves (EES) in a solid Ehrlich carcinoma model. Ehrlich cells were inoculated subcutaneously in the right pelvic member (2 × 106 cells) in female Swiss mice. The animals were treated with vehicle (10 mL kg-1, p.o.), EES (30 and 100 mg kg-1, p.o.), or methotrexate (2.5 mg kg-1, i.p.) for 21 days (early treatment) or 14 days (late treatment) after tumor inoculation, or 10 days before tumor inoculation and continued for 21 days after tumor inoculation (chemopreventive treatment). The acute toxicity test was performed according OECD guidelines Late treatment with EES had no antitumor effect. Early treatment with 100 mg kg-1 EES prevented tumor development, increased tumor necrosis factor-α (TNF-α) levels and decreased tumor superoxide dismutase (SOD) activity, interleukin-10 (IL-10) levels and Cyclin D1 expression, and tumor cell necrosis was observed. Chemopreventive treatment with EES for 10 and 31 days prevented tumor development in the same manner. EES treatment for 31 days decreased hepatic and tumor SOD activity, tumor IL-10 levels and Cyclin D1 expression, and increased tumor reduced glutathione, N-acetylglucosaminidase, reactive oxygen species, lipid peroxidation, TNF-α levels and Nrf2 expression. No toxicity was observed in the acute toxicity assay. In conclusion, EES had an antitumor effect by inhibiting Cyclin D1 expression and increasing inflammation with early and chemopreventive treatment. Modulation of the antioxidant system also contribute for the antitumor effects of EES.

The GLP-1 analog liraglutide attenuates acute liver injury in mice.

INTRODUCTION AND OBJECTIVES: Acute liver injury is a current health problem with few effective treatments. The present study investigated the hepatoprotective and curative potential of the glucagon-like peptide-1 analog liraglutide against carbon tetrachloride (CCl4)-induced hepatotoxicity. MATERIALS AND METHODS: Male Swiss mice were subjected to two protocols. The first protocol (Pretreatment) consisted of intraperitoneal (i.p.) treatment with liraglutide (0.057 and 0.118mgkg-1) or vehicle (distilled water) once daily for 7 days. On days 6 and 7, the animals were challenged with 2% CCl4 (5mgkg-1, i.p.). The second protocol (Late treatment) began with an injection of 5% CCl4 (5mgkg-1, i.p.) and subsequent treatment with liraglutide (0.057mgkg-1) or vehicle (distilled water) for 1 day. In both protocols, 24h after the last administration, blood and bile were collected from anesthetized animals, followed by euthanasia and liver collection. Plasma and bile underwent biochemical analyses, and histological, oxidative stress, and metabolic parameters were evaluated in the liver. RESULTS: Both liraglutide treatment protocols attenuated hepatotoxicity that was induced by CCl4, decreasing plasma levels of hepatic enzymes, stimulating the hepatic antioxidant system, and decreasing centrilobular necrosis, hepatic glycogen, and lipid accumulation. CCl4 tended to reduce bile lipid excretion, but liraglutide did not influence this parameter. CONCLUSIONS: The present results demonstrated the hepatoprotective and therapeutic effects of liraglutide, which may be attributable to a decrease in liver oxidative stress and the preservation of metabolism. Liraglutide may have potential as a complementary therapy for acute liver injury.

Detection molecular of Rangelia vitalii in dogs from Parana State, Southern Brazil / Detecção molecular de Rangelia vitalii em cães do Estado do Paraná, Sul do Brasil

Abstract Rangelia vitalii infects erythrocytes, leukocytes and endothelial cells of dogs. The present study aimed to report the molecular detection confirmed by sequencing of R. vitalii in the state of Paraná, as well as describe the clinical, hematological and biochemical alterations of the infected dogs. Three sick dogs from the metropolitan area of Curitiba, PR, Brazil, underwent a physical exam, and laboratory tests included hematology, biochemistry, polymerase chain reaction (PCR), and gene sequencing. Clinical signs included apathy, anorexia, and hemorrhage. Intra-erythrocytic and extracellular piroplasms were found on peripheral blood smears from all three dogs. Blood samples from these animals were positive for Babesia sp. by PCR targeting 18S rRNA. PCR products from all three dogs were sequenced, and BLAST analysis showed that the PCR-generated sequences were highly homologous with those of R. vitalii previously reported. Hematologic findings included severe anemia, shift of neutrophils to the regenerative left, and thrombocytopenia. Serum urea levels were increased in all three dogs, and direct bilirubin levels were elevated in one dog.

Resumo Rangelia vitalii infecta eritrócitos, leucócitos e células endoteliais de cães. O presente estudo objetivou relatar a detecção molecular confirmada por sequenciamento de R. vitalii no estado do Paraná e descrever as alterações clínicas, hematológicas e bioquímicas dos cães infectados. Três cães doentes da região metropolitana de Curitiba, PR, Brasil, foram submetidos a exame físico e exames laboratoriais que incluíram hematologia, bioquímica, reação em cadeia da polimerase (PCR) e sequenciamento genético. Os sinais clínicos incluíram apatia, anorexia e hemorragia. Piroplasmas intra-eritrocíticos e extracelulares foram encontrados em esfregaços de sangue periférico dos três cães. As amostras de sangue destes animais foram positivas para Babesia sp. pela PCR baseada no gene 18S rRNA. Os produtos de PCR dos três cães foram sequenciados e a análise de BLAST mostrou que as seqüências geradas por PCR eram altamente homólogas com as de R. vitalii previamente relatadas. Os achados hematológicos incluíram anemia grave, desvio de neutrófilos à esquerda regenerativo e trombocitopenia. Os níveis de uréia no soro aumentaram nos três cães, e os níveis de bilirrubina direta foram elevados em um cão.

Detection molecular of Rangelia vitalii in dogs from Parana State, Southern Brazil.

Rangelia vitalii infects erythrocytes, leukocytes and endothelial cells of dogs. The present study aimed to report the molecular detection confirmed by sequencing of R. vitalii in the state of Paraná, as well as describe the clinical, hematological and biochemical alterations of the infected dogs. Three sick dogs from the metropolitan area of Curitiba, PR, Brazil, underwent a physical exam, and laboratory tests included hematology, biochemistry, polymerase chain reaction (PCR), and gene sequencing. Clinical signs included apathy, anorexia, and hemorrhage. Intra-erythrocytic and extracellular piroplasms were found on peripheral blood smears from all three dogs. Blood samples from these animals were positive for Babesia sp. by PCR targeting 18S rRNA. PCR products from all three dogs were sequenced, and BLAST analysis showed that the PCR-generated sequences were highly homologous with those of R. vitalii previously reported. Hematologic findings included severe anemia, shift of neutrophils to the regenerative left, and thrombocytopenia. Serum urea levels were increased in all three dogs, and direct bilirubin levels were elevated in one dog.

Alterações no perfil da microbiota bucal durante permanência na UTI: colonização por patógenos respiratórios potenciais / Changes in the oral microbiota profile during ICU stay: colonization by potential respiratory pathogens / Alteraciones en el perfil de la microbiota bucal durante permanencia en la UTI: colonización por patógenos respiratorios potenciales

Introdução: Pacientes hospitalizados em Unidade de Terapia Intensiva (UTI) geralmente mostram má higiene bucal, o que contribui significativamente para o agravamento da contaminação local, com a presença de patógenos respiratórios potenciais. Objetivo: Caracterizar qualitativamente o perfil da microbiota bucal durante permanência na UTI, além da identificação de alterações bucais e salivares. Materiais e métodos: Foi realizado um estudo prospectivo em pacientes internados na UTI de um hospital oncológico, os quais foram avaliados clínica e microbiologicamente após 24 (T1), 72 (T2) e 120 (T3) horas consecutivas à admissão na UTI. Foram identificados os principais patógenos em cada momento e o perfil da microbiota oral foi comparado. Resultados: A amostra final foi de 30 pacientes, 23 homens e 7 mulheres, com idade média de 61 anos. Em T1, 96,67% dos pacientes apresentaram crescimento de microorganismos patogênicos, sendo identificados 14 tipos diferentes. Em T2 18 tipos de patógenos diferentes e em T3, 21 tipos, dos quais os mais prevalentes nas três coletas foram Staphylococcus não produtor de coagulase e Candida albicans. Clinicamente foram observados presença e progressão do biofilme visível (61%), cálculo (36,89%), condição periodontal deficiente (33,11%). Em relação à condição salivar verificou-se saburra lingual (92,11%), ressecamento labial (86,67%), hipossalivação (36,67%), assialia (52%) e escoamento salivar (8,89%). Conclusão: O biofilme do dorso de língua de pacientes em UTI pode representar um nicho considerável de patógenos respiratórios potenciais, uma vez que microorganismos etiológicos relacionados à pneumonia nosocomial foram isolados já no primeiro dia de internação, com a colonização subsequente por uma variedade de microorganismos predominantemente gram-negativos(AU)

Introduction: Hospitalized patients receiving treatment at Intensive Care Units (ICU) usually show poor oral hygiene, and may have the mouth and oropharingeal region colonized by pathogens involved in nosocomial pneumonia. The presence of these pathogens may increase the risk for respiratory diseases. OBJECTIVES: The aim of this study was to qualitatively characterize the oral microbiota profile of critical patients during ICU stay, besides the identification of oral and salivary alterations. Materials and Methods: A prospective study was carried out on patients admitted to the ICU from a cancer hospital, who were evaluated clinically and microbiologically (tongue-to-mouth swabs) after 24h (T1), 72h (T2) and within 120 consecutive hours (T3) after ICU admission to the ICU. The main pathogens were identified at each moment and the oral microbiota profile was compared. In addition, the major oral and salivary changes were identified. Results: The final sample consisted of 30 patients, 23 men and 7 women, with a mean age of 61 years. The reasons for hospitalization were 30% postoperative of oncological surgeries and 70% of medical emergencies. In T1, 96.67% of the patients presented growth of pathogenic microorganisms, being identified 14 different types. In T2, 18 different pathogen types were identified, and in T3, 21 pathogens, of which the most prevalent Coagulase negative staphylococcus and Candida albicans were the most prevalent in the three collections. It was observed the presence and progression of visible biofilm (61%), calculus (36.89%), poor periodontal condition (33.11%), partial teeth presence (26.67%), total edentulism (23.33%), cavities (10%), presence of residual root (20%). In relation to the salivary condition, there was accumulation of lingual (92.11%), labial dryness (86.67%), hyposalivation (36.67%), asialia (52%) and salivary flow (8.89%). Conclusion: The tongue dorsum biofilm of ICU patients may represent a considerable niche of potential respiratory pathogens, since etiological microorganisms related to nosocomial pneumonia were isolated on the first day of hospitalization, with subsequent colonization by a variety of microorganisms predominantly gram-negatives. The introduction of professional care directed to oral health and biofilm control in this group of patients could represent a significant contribution to the reduction of diseases to the health of the patient in the ICU(AU)

Introducción: Pacientes hospitalizados en UTI generalmente muestran mala higiene bucal, lo que contribuye significativamente al agravamiento de la contaminación local, con la presencia de patógenos respiratorios potenciales. Objetivo: Caracterizar cualitativamente el perfil de la microbiota bucal durante permanencia en la UTI, además de la identificación de alteraciones bucales y salivares. Materiales y métodos: Se realizó un estudio prospectivo en pacientes internados en la UTI de un hospital oncológico, los cuales fueron evaluados clínica y microbiológicamente después de 24 (T1), 72 (T2) y 120 (T3) horas consecutivas a la admisión en la UTI. Se identificaron los principales patógenos en cada momento y el perfil de la microbiota oral fue comparado. Resultados: La muestra final fue de 30 pacientes, 23 hombres y 7 mujeres, con edad media de 61 años. En T1, el 96,67% de los pacientes presentaron crecimiento de microorganismos patógenos, siendo identificados 14 tipos diferentes. En T2 18 tipos de patógenos diferentes y en T3, 21 tipos, de los cuales los más prevalentes en las tres colectas fueron Staphylococcus no productor de coagulasa y Candida albicans. Se observó la presencia y progresión del biofilme visible (61%), cálculo (36,89%), condición periodontal deficiente (33,11%). En cuanto a la condición salivar se verificó saburra lingual (92,11%), resecamiento labial (86,67%), hiposalivación (36,67%), asialia (52%) y flujo salivar (8,89%). Conclusión: El biofilm del dorso de lengua de pacientes en UTI puede representar un nicho considerable de patógenos respiratorios potenciales, ya que microorganismos etiológicos relacionados a la neumonía nosocomial se aislaron ya en el primer día de internación, con la colonización subsecuente por una variedad de microorganismos predominantemente gram-negativa(AU)

Effect of simvastatin on sensorial, motor, and morphological parameters in sciatic nerve crush induced-neuropathic pain in rats.

The present study compares the effects of a low and high doses of simvastatin in a model of peripheral neuropathy by evaluating sensorial, motor, and morphological parameters. First, male Wistar rats were orally treated with vehicle (saline, 1 mL/kg), simvastatin (2 and 80 mg/kg) or morphine (2 mg/kg, s.c.), 1 h before 2.5% formalin injection. Neuropathic pain was induced by crushing the sciatic nerve, and mechanical and cold allodynia, nerve function, histology, MPO and NAG concentrations, as well as mevalonate induced-nociception were evaluated. Animals were orally treated with vehicle, simvastatin, or gabapentin (30 mg/kg) for 18 days. Simvastatin (2 and 80 mg/kg) reduced the inflammatory pain induced by formalin, but failed to decrease the paw edema. Mechanical allodynia was reduced by the simvastatin (2 mg/kg) until the 12th day after injury and until the 18th day by gabapentin. However, both simvastatin and gabapentin treatments failed in attenuated cold allodynia or improved motor function. Interestingly, both doses of simvastatin showed a neuroprotective effect and inhibited MPO activity without altering kidney and hepatic parameters. Additionally, only the higher dose of simvastatin reduced the cholesterol levels and the nociception induced by mevalonate. Our results reinforce the antinociceptive, antiallodynic, and anti-inflammatory effects of oral simvastatin administration, which can strongly contribute to the sciatic nerve morphology preservation. Furthermore, our data suggest that lower and higher doses of simvastatin present beneficial effects that are dependent and independent of the mevalonate pathway, respectively, without causing signs of nerve damage.

Vitamin C Improves Gastroparesis in Diabetic Rats: Effects on Gastric Contractile Responses and Oxidative Stress.

BACKGROUND: Diabetic gastroparesis is a common complication of diabetes mellitus, which mainly affects women. Previous studies have demonstrated that oxidative stress is involved in its onset and development. AIMS: This study evaluated the role of vitamin C on diabetes-associated gastric dysmotility. METHODS: Female rats with streptozotocin-induced diabetes were treated with vehicle (water, 1 mL/kg, p.o.), vitamin C (300 mg/kg/day, p.o.), or insulin (6 IU/day, s.c.). Gastric emptying, in vitro gastric contractility, and biochemistry parameters were analyzed at the end of the treatment (i.e. 8 weeks after the diabetes induction). RESULTS: Vitamin C reversed the delayed gastric emptying of diabetic rats to normal levels, and avoided the changes in the contractile responses to acetylcholine (0.1 nM-1 µM), but not to 5-hydroxytryptamine (0.1 nM-1 µM), in the pylorus and fundus from diabetic rats. Moreover, the contraction evoked by KCl (40 mM) in the fundus, but not in the pylorus, was intensely increased in diabetic rats treated with vitamin C. Notably, the vitamin C reestablished the reduced glutathione levels by 77% and decreased the reactive oxygen species content by 60% in the gastric tissue from diabetic rats. Despite the effects on gastric motility, vitamin C treatment did not change the fasting glycaemia or the glycated hemoglobin of diabetic rats. Unsurprisingly, insulin treatment normalized all parameters evaluated. CONCLUSIONS: Vitamin C exhibited a remarkable beneficial effect on gastric emptying dysfunction in diabetic rats, which was mediated by attenuation of oxidative stress and maintenance of the cholinergic contractile responses in fundus and pylorus.

Detection molecular of Rangelia vitalii in dogs from Parana State, Southern Brazil

Abstract Rangelia vitalii infects erythrocytes, leukocytes and endothelial cells of dogs. The present study aimed to report the molecular detection confirmed by sequencing of R. vitalii in the state of Paraná, as well as describe the clinical, hematological and biochemical alterations of the infected dogs. Three sick dogs from the metropolitan area of Curitiba, PR, Brazil, underwent a physical exam, and laboratory tests included hematology, biochemistry, polymerase chain reaction (PCR), and gene sequencing. Clinical signs included apathy, anorexia, and hemorrhage. Intra-erythrocytic and extracellular piroplasms were found on peripheral blood smears from all three dogs. Blood samples from these animals were positive for Babesia sp. by PCR targeting 18S rRNA. PCR products from all three dogs were sequenced, and BLAST analysis showed that the PCR-generated sequences were highly homologous with those of R. vitalii previously reported. Hematologic findings included severe anemia, shift of neutrophils to the regenerative left, and thrombocytopenia. Serum urea levels were increased in all three dogs, and direct bilirubin levels were elevated in one dog.

Resumo Rangelia vitalii infecta eritrócitos, leucócitos e células endoteliais de cães. O presente estudo objetivou relatar a detecção molecular confirmada por sequenciamento de R. vitalii no estado do Paraná e descrever as alterações clínicas, hematológicas e bioquímicas dos cães infectados. Três cães doentes da região metropolitana de Curitiba, PR, Brasil, foram submetidos a exame físico e exames laboratoriais que incluíram hematologia, bioquímica, reação em cadeia da polimerase (PCR) e sequenciamento genético. Os sinais clínicos incluíram apatia, anorexia e hemorragia. Piroplasmas intra-eritrocíticos e extracelulares foram encontrados em esfregaços de sangue periférico dos três cães. As amostras de sangue destes animais foram positivas para Babesia sp. pela PCR baseada no gene 18S rRNA. Os produtos de PCR dos três cães foram sequenciados e a análise de BLAST mostrou que as seqüências geradas por PCR eram altamente homólogas com as de R. vitalii previamente relatadas. Os achados hematológicos incluíram anemia grave, desvio de neutrófilos à esquerda regenerativo e trombocitopenia. Os níveis de uréia no soro aumentaram nos três cães, e os níveis de bilirrubina direta foram elevados em um cão.

Hydroethanolic extract of Baccharis trimera ameliorates alcoholic fatty liver disease in mice.

Ethanol abuse is a serious public health problem that is associated with several stages of alcoholic liver disease (ALD) and a high incidence of morbidity and mortality. Alcoholic fatty liver disease (AFLD), the earliest stage of ALD, is a multifactorial injury that involves oxidative stress and disruptions of lipid metabolism. Although benign and reversible, no pharmacological treatments are available for this condition. In the present study, we induced AFLD in mice with 10% ethanol and a low-protein diet and then orally treated them with a hydroethanolic extract of Baccharis trimera (HEBT; 30 mg kg-1). HEBT reversed ethanol-induced oxidative stress in the liver, reduced lipoperoxidation, normalized GPx, GST, SOD and Cat activity, and GSH and total ROS levels. The reverser effect of HEBT was observed upon ethanol-induced increases in the levels of plasma and hepatic triglycerides, plasma cholesterol, plasma high-density lipoprotein, and plasma and hepatic low-density lipoprotein. Moreover, HEBT increased fecal triglycerides and reduced the histological ethanol-induced lesions in the liver. HEBT also altered the expression of genes that are involved in ethanol metabolism, antioxidant systems, and lipogenesis (i.e., CypE1, Nrf2, and Scd1, respectively). No signs of toxicity were observed in HEBT-treated mice. We propose that HEBT may be a promising pharmacological treatment for AFLD.

Hematologic and Biochemical Values of Wild Red-Tailed Amazon Parrot (Amazona brasiliensis) Nestlings With Abnormal Clinical Examination in Rasa Island, Brazil.

The red-tailed Amazon parrot (Amazona brasiliensis) is an endangered psittacine species, but little information is available about abnormal clinical findings and hematologic and biochemical values of this species, which are important for monitoring the health of this population. To determine hematologic and biochemical values for wild red-tailed parrot nestlings exhibiting abnormal clinical findings, 31 nestlings from the Rasa Island (Paraná State, Southern Brazil) were physically restrained for clinical examination and blood sample collection. On physical examination, 26 birds had mild abnormalities and 5 had severe disorders. Parrots were divided into 5 groups according to the following clinical findings: presence of ectoparasites (group 1), respiratory disorders (group 2), chronic skin lesions caused by fly larvae (group 3), beak disorders (group 4), and severe clinical signs (group 5). Abnormal hematologic and biochemical findings in the nestlings were high total protein in group 3; low values for hemoglobin and mean corpuscular hemoglobin concentration in group 4; low glucose concentration, high mean absolute heterophil count, and high heterophil : lymphocyte ratio in group 5; high concentrations of total plasma protein in groups 3 and 4; and high globulin concentration in groups 3 and 5. In general, the population assessed was in good condition. These results provide a guide to the expected clinical findings associated with hematologic and biochemical concentrations in a population of free-living parrots with abnormal clinical examination findings. The data support the conservation planning and health monitoring of the endangered red-tailed Amazon parrot.

Sydnone 1: A Mesoionic Compound with Antitumoral and Haematological Effects In Vivo.

This study evaluated the antitumour activity of the mesoionic compound sydnone 1 (Syd-1) against Walker-256 carcinosarcoma. Tumour cells were subcutaneously inoculated in the hind limb in male Wistar rats. The animals were orally treated for 12 days with Syd-1 (75 mg/kg) or vehicle. At the end of treatment, considerable decreases in tumour volume and tumour weight were observed in treated animals. Samples of these tumours presented increases in apoptotic bodies and pro-apoptotic protein expression (Bax and p53), while the expression of the anti-apoptotic protein Bcl-2 was reduced. A decrease in reduced glutathione levels and an increase in glutathione peroxidase activity were observed in tumour after Syd-1 treatment. However, significant splenomegaly was evident in animals that received Syd-1, most likely attributable to the induction of haemolysis. This study demonstrated the antitumour activity of Syd-1 against Walker-256 carcinosarcoma. Its mechanism of action is linked to the activation of apoptotic pathways that lead to tumour cell death.

Sesquiterpene lactones of Moquiniastrum polymorphum subsp. floccosum have antineoplastic effects in Walker-256 tumor-bearing rats.

BACKGROUND AND AIM: This study aimed to evaluate the in vivo antitumor actions and toxicity of the dichloromethane fraction (F1B) of Moquiniastrum polymorphum subsp. floccosum (formerly Gochnatia polymorpha ssp. floccosa), composed of sesquiterpene lactones, against Walker-256 carcinosarcoma in rats. METHODS: Male Wistar rats received 100 mg kg(-1) F1B per day orally for 16 days after subcutaneous inoculation of Walker-256 cells in the pelvic limb. The tumor progression was monitored, and after treatment, tumor weight, oxidative stress, plasma biochemistry, inflammatory parameters, gene expression and histology of tumor and/or liver were evaluated. The toxicity of F1B was analyzed through the relative weight of organs. Additionally, an LD50 test was performed in mice. RESULTS: F1B treatment significantly reduced tumor volume and weight. There was no difference in oxidative stress in tumor tissue after treatment. F1B treatment modified hepatic glutathione and superoxide dismutase, and normalized plasma glucose, alkaline phosphatase, and amylase. F1B did not affect the activity of myeloperoxidase and N-acetylglucosaminidase or the nitric oxide levels in tumor tissue. However, F1B decreased the tumor necrosis factor (TNF)-α levels. Additionally, F1B increased apoptosis in the tumor, mediated by up-regulation of the p53 and Bax gene expression. No clinical signs of toxicity or death were observed in the rats treated with F1B. The LD50 calculated for mice was 1209 mg kg(-1). CONCLUSIONS: F1B, which is rich in sesquiterpene lactones, showed antitumor activity against Walker-256 carcinosarcoma. This effect may be, at least in part, related to the induction of apoptosis and inhibition of TNF-α signaling.

Proteínas de fase aguda em cadelas com neoplasia mamária / Acute phase proteins in female dogs with mammary tumors

As proteínas de fase aguda (PFA) apresentam concentrações séricas alteradas mediante processos infecciosos, inflamatórios e neoplásicos. Objetivou-se com este trabalho avaliar as variações séricas das PFA em cadelas portadoras de neoplasia mamária, comparando com a avaliação histológica e leucograma. As PFA foram avaliadas em 45 cadelas com tumor de mama, distribuídas nos grupos neoplasia benigna (n=13), maligna não ulcerada (n=24) e maligna ulcerada (n=8). O grupo controle foi composto por 20 cadelas saudáveis. Foram realizados o teste de eletroforese em gel de poliacrilamida contendo dodecil sulfato de sódio (SDS-PAGE) para identificar as PFA (albumina, ceruloplasmina, transferrina, haptoglobina Hp, α-1 antitripsina e α-1 glicoproteina ácida) e o teste ultrassensível para proteína C reativa (PCR). As pacientes com neoplasia mamária maligna ulcerada apresentaram elevações sérica para PCR e Hp e redução da albumina (P<0,05, One-Way ANOVA e Teste de Dunn). Nessas pacientes, foi observada correlação positiva entre o leucograma inflamatório e o aumento das PFA (P=0,002, Teste de Fisher) e não foram observadas correlações entre as PFA e os subtipos histológicos. Conclui-se que avaliações conjuntas da PCR, Hp e albumina podem ser utilizadas como ferramenta de auxílio diagnóstico e prognóstico em cadelas com neoplasia mamária.

Acute phase proteins (APPs) are serum proteins whose concentrations change after infectious and inflammatory disease, and cancer. The aims of this study were to evaluate changes in APPs concentration and to correlate these findings with histological classification and WBC in female dogs with mammary tumors. APPs were studied in 45 female dogs with mammary tumor distributed in the following groups: benign (n=13), malignant without tumor ulceration (n=24), and malignant with tumor ulceration (n=8). SDS-polyacrylamide gel (SDS-PAGE) electrophoresis was used to measure APPs concentrations (albumin, ceruloplasmin, transferrin, haptoglobinHp, α-1-acid glycoprotein and α-1-antitrypsin) and ultrasensitive assay was used to evaluate serum C-reactive protein (CRP). Patients with malignant mammary neoplasia plus ulceration had significant increase of CRP and Hp, and had decreased levels of albumin (P<0.05, One-Way ANOVA and Dunn Test). Positive correlation among APPs and inflammatory leukocytosis were observed (P=0.002, Fisher test). No correlation was observed between APPs and histological subtype. In conclusion, combined changes of CRP, Hp and albumin may be used as a prediagnostic tool and prognosis in dogs with mammary tumors.