Decreased levels of cathepsin Z mRNA expressed by immune blood cells: diagnostic and prognostic implications in prostate cancer

Cathepsin Z (CTSZ) is a cysteine protease responsible for the adhesion and migration of both immune and tumor cells. Due to its dual role, we hypothesized that the site of CTSZ expression could be determinant of the pro- or anti-tumorigenic effects of this enzyme. To test this hypothesis, we analyzed CTSZ expression data in healthy and tumor tissues by bioinformatics and evaluated the expression levels of CTSZ mRNA in the blood cells of prostate cancer (PCa) patients by qRT-PCR compared with healthy subjects, evaluating its diagnostic and prognostic implications for this type of cancer. Immune cells present in the blood of healthy patients overexpress CTSZ. In PCa, we found decreased CTSZ mRNA levels in blood cells, 75% lower than in healthy subjects, that diminished even more during biochemical relapse. CTSZ mRNA in the blood cells had an area under the curve for PCa diagnosis of 0.832, with a 93.3% specificity, and a positive likelihood ratio of 9.4. The site of CTSZ mRNA expression is fundamental to determine its final role as a protective determinant in PCa, such as CTSZ mRNA in the blood cells, or a malignant determinant, such as found for CTSZ expressed in high levels by different types of primary and metastatic tumors. Low CTSZ mRNA expression in the total blood is a possible PCa marker complementary to prostate-specific antigen (PSA) for biopsy decisions, with the potential to eliminate unnecessary biopsies.

Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

Considering that osteoarthritis (OA) is the most prevalent joint disease worldwide, multiple pharmacological treatments have been proposed to alter the articular structure with potential benefit in the progression of the disease. The so-called disease-modifying OA drugs have been frequently investigated but conclusive findings are rare. Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects in decreasing the risk of fractures and possible effect in reducing the progression of OA. The objective of this review was to demonstrate the current panorama of knowledge on the use of SrRan in clinical and experimental models, clarifying its mechanisms of action and describing possible anti-nociceptive and anti-inflammatory effects. The systematic review was based on the PRISMA statement and included articles that are indexed in scientific databases. Fifteen studies were included: seven pre-clinical and eight clinical studies. Despite the limited number of studies, the results suggest a positive effect of SrRan in patients with OA, through changes in functional capacity and reduction of progression of morphological parameters and joint degradation, with moderate quality of evidence for those clinical outcomes. Novel studies are necessary to elucidate the molecular targets of SrRan, focusing on anti-inflammatory effects and histological changes promoted by SrRan, which seemed to reduce the progression of OA in the experimental and clinical studies.

Intestinal cell migration damage induced by enteropathogenic Escherichia coli strains

Epithelial cell migration is an essential response to enteric pathogens such as enteropathogenic Escherichia coli (EPEC). This study aimed to investigate the effects of EPEC infection on intestinal epithelial cell migration in vitro, as well as the involvement of type III secretion system (T3SS) and Rho GTPases. Crypt intestinal epithelial cells (IEC-6) were infected with EPEC strains (E2348/69, ΔescF, and the LDI001 strain isolated from a malnourished Brazilian child) and commensal E. coli HS. Wound migration and cell death assays were performed at different time-points. Transcription and expression of Rho GTPases were evaluated using real-time PCR and western blotting. Overall, EPEC E2348/69 reduced migration and increased apoptosis and necrosis levels compared to EPEC LDI001 and E. coli HS strains. Moreover, EPEC LDI001 impaired cell migration at a higher level than E. coli HS and increased necrosis after 24 hours compared to the control group. The different profiles of virulence genes between the two wild-type EPEC strains, characterized by the absence of espL and nleE genes in the LDI001, might explain the phenotypic results, playing significant roles on cell migration impairment and cell death-related events. Moreover, the type III secretion system is determinant for the inhibition of intestinal epithelial cell migration by EPEC 2348/69, as its deletion prevented the effect. Active Rac1 concentrations were increased in E2348/69 and LDI001-infected cells, while the T3SS-deficient strain did not demonstrate this activation. This study contributes with valuable insight to characterize the mechanisms involved in the impairment of intestinal cell migration induced by EPEC.

Microbiota bacteriana de ovos de jacaré-do-pantanal incubados naturalmente / Bacterial microbiota of the Pantanal caiman eggs incubated in nature

A cadeia produtiva do Caiman yacare tem-se destacado no Mato Grosso com a exportação de 143.386 peles em 2015, cujo sistema de manejo (ranching) implica a incubação artificial dos ovos. Nesse processo, a contaminação bacteriana de ovos influencia a taxa de eclosão. O conhecimento da microbiota de ovos incubados naturalmente orienta o manejo sanitário adequado no incubatório. No presente estudo, são apresentadas informações sobre essa microbiota e sua correlação com a de outros crocodilianos, apontando-se as espécies com potencial patogênico. Amostras de 20 ninhos de C. yacare foram coletadas e semeadas em ágar sangue e ágar Mac Conckey. A colônia condizente com Salmonella sp. foi confirmada pela técnica de reação em cadeia de polimerase. Das 22 espécies bacterianas isoladas, 59% pertencem à família Enterobacteriaceae e 41% a outros táxons bacterianos. A semelhança dos achados com as bactérias isoladas na microbiota oral e/ou intestinal/cloacal de crocodilianos foi de 77,27%. As bactérias mais e menos frequentes foram, respectivamente, Bacillus cereus, Flavobacterium multivorum, Citrobacter freundii, Escherichia hermannii, Hafnia alvei, Morganella, morganni, Salmonella sp., Serratia marcescens e Shigella sonnei. Das bactérias isoladas, 86,36% têm potencial patogênico para crocodilianos. A origem materna e a ambiental da microbiota de ovos incubados naturalmente são, respectivamente, de 77,27% e 27,27%.(AU)

The Pantanal caiman productive chain has grown in Mato Grosso with the exportation of 143.383 leather pieces in 2015, whose management system (ranching) implies the artificial incubation of eggs. In this process, the bacterial contamination of the eggs influences the hatching rate. Knowledge of the naturally incubated microbiota of eggs guides the appropriate sanitary management in the incubator room. Here we present information about this microbiota and correlate it with that of other crocodilians, indicating the species with pathogenic potential. Samples were collected in 20 nests at Pantanal, and sown in blood and Mac Conckey agar. Salmonella sp. was confirmed through polymerase chain reaction technique. From the twenty-two different species of bacteria isolated, 59% are from the Enterobacteriaceae Family and 41% from other bacterial taxonomies. The similarity of findings to isolated bacteria in the crocodilians oral and/or intestinal/cloacal microbiota was of 77,27%. The most and least frequent bacteria were, respectively, Bacillus cereus, Flavobacterium multivorum and Citrobacter freundii and Escherichia hermannii, Hafnia alvei, Morganella, morganni, Salmonella sp., Serratia marcescens and Shigella sonnei. Among the isolated bacteria, 86,36% are pathogenic for crocodilians. The maternal and environmental origin of the microbiota of eggs naturally incubated is, respectively, of 77,27% and 27,27%.(AU)

Estabelecimento in vitro e aclimatização de Lippia alba (Mill. ) N. E. Brown / In vitro establishment and acclimatization of Lippia alba (Mill. ) N. E. Brown

O presente trabalho teve por objetivo estabelecer in vitro a espécie Lippia alba (Mill.) N. E. Brown e promover a aclimatização de mudas dessa espécie. Para isso, foi testada a influência de diferentes concentrações e tempos de imersão em hipoclorito de sódio na assepsia dos explantes. Segmentos nodais foram imersos em hipoclorito de sódio nas concentrações 0,4; 0,6; 0,8 e 1,0 % e nos tempos 8, 12 e 16 minutos. Após 30 dias avaliou-se a contaminação bacteriana (%), número de brotos, número de folhas, e a taxa de sobrevivência (%). A concentração de 1% de hipoclorito de sódio foi a mais eficiente no controle da contaminação. Ápices caulinares de L. alba foram estabelecidos in vitro em meio MS suplementado com diferentes doses de BAP (0; 0,5; 1,0; 1,5 mg L-1). Após 140 dias avaliou-se a contaminação (%), a taxa de sobrevivência (%), a oxidação (%) e o número de brotos. Os melhores resultados foram obtidos para a dose 1,5 mg L-1 deste regulador. Para a aclimatização foram testados quatro tipos de substratos: pó de coco + calcário (1 g L-1), Plantmax® + calcário (1 g L-1), vermiculita + calcário (1 g L-1) e pó de coco + Plantmax® + vermiculita (1:1:1) + calcário (1 g L-1). Avaliou-se a taxa de sobrevivência (%), comprimento da parte aérea (cm), comprimento da raiz (cm), massa fresca da parte aérea e da raiz (g), e a massa seca da parte aérea e da raiz (g). Os melhores resultados foram obtidos quando com o substrato comercial Plantmax®.

The present study aimed to establish the species Lippia alba (Mill.) N. E. Brown in vitro and promote the acclimatization of the seedlings of this species. Therefore, we tested the effect of different concentrations and immersiog times in sodium hypochloritetfor the disinfection of explants. Nodal segments were immersed in sodium hypochlorite at the different concentrations of ,.4; ,.6; ,.8 and ,.0% during the different times of 8, 12 and 16 minutes. After 30 days, bacterial contamination (%), number of shoots, number of leaves and survival rate (%) were evaluated. The 1% concentration of sodium hypochlorite was more effective in controlling contamination. Shoot apices of L. alba were established in vitro on MS medium supplemented with different concentrations of BAP (;, ,.5; ,.0; ,.5 mg L-1). After 140 days, we evaluated the contamination (%), survival rate (%), oxidation (%) and number of shoots. The best results were obtained when we used the dose of ,.5 mg L-1 of this regulator. For acclimatization, we tested four types of substrates: coconut powder + lime (1 g L-1), Plantmax® + lime (1 g L-1), vermiculite + lime (1 g L-1) and coconut powder + Plantmax® + vermiculite (1:1:1) + lime (1 g L-1). We evaluated the survival rate (%), shoot length (cm), root length (cm), fresh weight of shoot and root (g) and dry weight of shoot and root (g). The best results were obtained when using the substrate Plantmax®.

Mordedura canina e atendimento antirrábico humano em Minas Gerais / Dog bite and human anti-rabies healthcare, Minas Gerais

O objetivo do presente trabalho foi descrever e avaliar a mordedura canina e o atendimento antirrábico humano em Minas Gerais, de 1999 a 2004, correlacionando fontes de informação e áreas de risco predeterminadas para raiva humana transmitida por cão. Realizou-se um estudo observacional descritivo retrospectivo, utilizando-se, de forma adaptada, a análise exploratória de prontuários dos atendimentos da Superintendência de Epidemiologia da Secretaria de Estado da Saúde de Minas Gerais (339.012 de atendimentos), do Sistema de Informação de Notificação de Agravos, do Sistema de Informações sobre Mortalidade, do Sistema de Informações Hospitalares e do Programa Nacional de Imunizações (132.452 fichas). Para a classificação dos agravos, usou-se o Código Internacional de Doenças (10ª revisão). Os dados foram armazenados e analisados com auxílio dos softwares Epi-Info, Tab-Win e Office®. Verificou-se que o tratamento antirrábico humano é excessivo nas áreas de baixo e médio risco para raiva e, ao contrário, reduzido nas áreas de alto risco. O perfil do paciente é estudante masculino, menor de 14 anos, residente em área urbana de baixo risco para raiva humana transmitida por cão, com mordedura única nos membros, provocada por cão sadio e observável. Os sistemas de informação não oferecem a confiabilidade necessária ao médico responsável para a prescrição do tratamento antirrábico adequado. A profilaxia da raiva deve ter um aspecto multicêntrico, com interfaces na atenção tanto à saúde humana quanto à animal, o que não tem ocorrido, propiciando falhas na vigilância e no atendimento do agravo.

The objective of the present paper is describe and evaluate dog bite and some aspects of anti-rabid human care in Minas Gerais during five years, correlating the sources of information and epidemiological risk areas defined for human rabies transmitted by dogs in the State. We performed an observational retrospective study by adapted exploration form analysis, from 1999 to 2004, using databases of Epidemiology of Minas Gerais and National Information Systems of reportable disease, Immunization, Mortality, Hospitalization, International Code of Diseases (10th revision). The areas of risk for human rabies transmitted by dogs were pre determined. The dog bite is still the main complaint that leads to care. The profile of the patient is a male student, under 14 years of age, with a single wound in members, resident in an urban low risk area for human rabies transmitted by dogs, and is healthy and observable. The treatment is excessive in areas of low and medium risk. In high-risk areas, there is a low indication of treatment. Information systems do not offer the reliability required by the doctor responsible for prescribing the appropriate anti-rabies treatment. Rabies prophylaxis should have a multi-centre aspect, with interfaces in attention to health and veterinary, which has not occurred, providing surveillance failures.

Métodos de secagem e rendimento dos extratos de folhas de Plectranthus barbatus (boldo-da-terra) e P. ornatus (boldo-miúdo) / Methods estimated drying and percentage of extracts in leaves of Plectranthus barbatus (Brazilian bold) and P. ornatus (false bold)

Plectranthus sp. pertence à família Lamiaceae e inclui cerca de 300 espécies. Duas delas, P. barbatus (PB) e P. ornatus (PO) destacam-se pelo interesse medicinal. As principais substâncias encontradas em Plectranthus sp. são os diterpenóides, óleos essenciais e compostos fenólicos. A melhor forma de utilizar as folhas de PB e PO é a fresco; porém, na comercialização há necessidade de recorrer a processos de secagem. Entretanto, isto pode interferir no princípio ativo, desta forma, estudos para determinar o melhor método gravimétrico são importantes. O objetivo deste estudo foi avaliar qual o melhor método de secagem, onde haja maior perda de água possível, e calcular os rendimentos dos extratos visando avaliar se o método gravimétrico interfere na quantidade de extrato produzido. Desta forma, utilizou-se quatro métodos de secagem e após evaporação do solvente, fez-se o cálculo do rendimento dos extratos secos. O percentual de água foi superior em PB e PO (média geral de 90,12±8,22 por cento). Dentre as secagens, em estufa de ventilação forçada (EVF) foi mais eficiente em PB (88,87 por cento) e em estufa convencional (ECO) foi melhor em PO (95,13 por cento). O maior rendimento do extrato seco em PB foi na secagem em camada delgada (CD) (20,96 por cento), enquanto que em PO foi ECO (41,34 por cento). Não houve correlação entre o método de secagem e o rendimento de extrato obtido.

Plectranthus sp. belongs to the family Lamiaceae and includes about 300 species. Two of them, P. barbatus (PB) and P. ornatus (PO), have medicinal interest. The main substances found in Plectranthus sp. are the diterpenoids, essential oils and phenolic compounds. The best way to use the leaves of PB and PO is cool; but for marketing there is a need of resort to drying processes. However, this may interfere on the values of active principle; thus, studies to determine the best gravimetric methods are important. The objective of this study was to evaluate the best method of drying, where there the greater loss of water possible, and calculate the percentage of the extracts to assess whether the gravimetric method interferes with the amount of extract produced. To this was done by drying four different methods ventilated dry (EVF), conventional drying (ECO), microwave (MCO) and layer thing (CD) and after evaporation of the solvent, was made the calculation the percentage of the dried extract. The water content was higher in PB and PO (overall average of 90.12±8.22 percent). Among the drying, EVF was more efficient for PB (88.87 percent) and ECO was better for PO (95.13 percent). The highest content of dry extract was for PB in to CD (20.96 percent), whereas for PO was in to ECO (41.34 percent). There is no relationship between the drying method and in the quantity of extract obtained.

Coronary artery calcification is associated with insulin resistance index in patients with type 1 diabetes

The objective of the present study was to evaluate the risk factors associated with the presence of coronary artery calcification (CAC) in patients with type 1 diabetes (T1D). A cross-sectional study was conducted on 100 consecutive T1D patients without coronary artery disease, with at least 5 years of diabetes and absence of end-stage renal disease. Mean age was 38 ± 10 years and 57 percent were males. CAC score was measured by multidetector computed tomography (Siemens Sensation 64 Cardiac). The insulin resistance index was measured using the estimated glucose disposal rate (eGDR). The eGDR was lower among CAC-positive patients than among CAC-negative patients, suggesting an increased insulin resistance. In a logistic regression model adjusted for age (at 10-year intervals), eGDR, diabetic nephropathy and gender, CAC was associated with age [OR = 2.73 (95 percentCI = 1.53-4.86), P = 0.001] and with eGDR [OR = 0.08 (95 percentCI = 0.02-0.21), P = 0.004]. In T1D subjects, insulin resistance is one of the most important risk factors for subclinical atherosclerosis.

Effect of metabolic syndrome and of its individual components on renal function of patients with type 2 diabetes mellitus

The objective of this study was to evaluate the effect of metabolic syndrome (MetS) and its individual components on the renal function of patients with type 2 diabetes mellitus (DM). A cross-sectional study was performed in 842 type 2 DM patients. A clinical and laboratory evaluation, including estimated glomerular filtration rate (eGFR) calculated by the modification of diet in renal disease formula, was performed. MetS was defined according to National Cholesterol Education Program - Adult Treatment Panel III criteria. Mean patient age was 57.9 ± 10.1 years and 313 (37.2 percent) patients were males. MetS was detected in 662 (78.6 percent) patients. A progressive reduction in eGFR was observed as the number of individual MetS components increased (one: 98.2 ± 30.8; two: 92.9 ± 28.1; three: 84.0 ± 25.1; four: 83.8 ± 28.5, and five: 79.0 ± 23.0; P < 0.001). MetS increased the risk for low eGFR (<60 mL·min-1·1.73 (m²)-1) 2.82-fold (95 percentCI = 1.55-5.12, P < 0.001). Hypertension (OR = 2.2, 95 percentCI = 1.39-3.49, P = 0.001) and hypertriglyceridemia (OR = 1.62, 95 percentCI = 1.19-2.20, P = 0.002) were the individual components with the strongest associations with low eGFR. In conclusion, there is an association between MetS and the reduction of eGFR in patients with type 2 DM, with hypertension and hypertriglyceridemia being the most important contributors in this sample. Interventional studies should be conducted to determine if treatment of MetS can prevent renal failure in type 2 DM patients.

Diabetic retinopathy is associated with early autonomic dysfunction assessed by exercise-related heart rate changes

Diabetic retinopathy has been associated with cardiac autonomic dysfunction in both type 1 and type 2 diabetes mellitus (DM) patients. Heart rate (HR) changes during exercise testing indicate early alterations in autonomous tonus. The aim of the present study was to investigate the association of diabetic retinopathy with exercise-related HR changes. A cross-sectional study was performed on 72 type 2 and 40 type 1 DM patients. Autonomic dysfunction was assessed by exercise-related HR changes (Bruce protocol). The maximum HR increase, defined as the difference between the peak exercise rate and the resting rate at baseline, and HR recovery, defined as the reduction in HR from the peak exercise to the HR at 1, 2, and 4 min after the cessation of the exercise, were determined. In type 2 DM patients, lower maximum HR increase (OR = 1.62, 95 percentCI = 1.03-2.54; P = 0.036), lower HR recovery at 2 (OR = 2.04, 95 percentCI = 1.16-3.57; P = 0.012) and 4 min (OR = 2.67, 95 percentCI = 1.37-5.20; P = 0.004) were associated with diabetic retinopathy, adjusted for confounding factors. In type 1 DM, the absence of an increase in HR at intervals of 10 bpm each during exercise added 100 percent to the odds for diabetic retinopathy (OR = 2.01, 95 percentCI = 1.1-3.69; P = 0.02) when adjusted for DM duration, A1c test and diastolic blood pressure. In conclusion, early autonomic dysfunction was associated with diabetic retinopathy. The recognition of HR changes during exercise can be used to identify a high-risk group for diabetic retinopathy.

Photo-oxidative damage to isolated rat liver mitochondria induced by phenothiazines

Photosensitization is a well-known side-effect of phenothiazines that could involve photochemically promoted oxidative damage to mitochondria, leading to the impairment of metabolic functions and apoptosis. In this work, for the first time, we investigated the effects of photoexcited thioridazine (TR), trifluoperazine (TFP) and fluphenazine (FP) on isolated rat liver mitochondria. Under UV irradiation, the presence of these phenothiazines led to a dose-dependent lack of the respiratory control ratio. These effects were not accompanied by significant swelling and oxidation of protein thiol groups but were accompanied by lipid peroxidation. Lycopene and sorbate, well-known quenchers of singlet oxygen and triplet species, respectively, were ineffective at protecting mitochondrial lipids against the damage promoted by the excited phenothiazines, suggesting that photochemically-produced cation radicals were the pro-oxidant species. Corroborating this proposal, butylated hydroxytoluene (BHT) completely inhibited the lipid peroxidation induced by UV irradiation in the presence of phenothiazines. These novel results make a significant contribution to the understanding of the photochemical properties of phenothiazines in biological systems

Fibrilação atrial no idoso: uma abordagem prática / Atrial fibrillation in the elderly: a practical approach

A incidência da fibrilação atrial aumenta com a idade, bem como as complicaçöes decorrentes dela própria e de seu tratamento, isto é, a anticoagulação. A principal complicação é a embolia cerebral, aumentada no idoso. Infelizamente, a incidência de complicaçöes hemorrágicas graves devido aos anticoagulantes está também aumentada e o ácido acetilsalicílico não se mostrou muito eficaz nessa faixa etária. A disfunção diastólica e as cardiopatias usualmente concomitantes tornam o idoso particularmente sensível às alteraçöes hemodinâmicas impostas pela fibrilação atrial, não sendo raras a dispnéia, as palpitaçöes constantes, a insufuciência cardíaca e as síncopes. Sendo assim, os autores propöem uma ênfase maior na tentativa de restauração e manutenção do ritmo sinusal nessa população, a fim de evitar a ocorrência de embolias sistêmicas sem o risco de hemorragias, além de proporcionar melhora mais eficaz da sintomatologia.