Exploring Life History Choices: Using Temperature and Substrate Type as Interacting Factors for Blowfly Larval and Female Preferences.

Blowflies (Diptera: Calliphoridae) present a wide range of larval lifestyles, typically classified as obligate parasitism, facultative parasitism, and complete sapro-necrophagy. Several parasitic species, both obligate and facultative, are considered to be of sanitary and economic importance, as their larvae can cause myiasis (maggot infestation in live tissue). However, it is noteworthy that the adult female plays a decisive role as she chooses the oviposition site, and, therefore, largely determines the feeding habit and developmental conditions of the larvae. In this study, two protocols are proposed to test larval feeding preference and female oviposition site preference considering two interacting factors: meat substrate type and temperature. The setups presented here allowed to test Lucilia cuprina larvae and gravid females in a four-choice assay with two temperatures (33 ± 2 °C and 25 ± 2 °C) and two types of meat substrates (fresh meat supplemented with blood and 5-day-old rotten meat). Larvae or gravid females can choose to burrow or lay their eggs, respectively, in either of the following: rotten meat at 25 °C (simulating a necrophagous species condition), fresh meat supplemented with blood at 33 °C (simulating a parasitic species condition), and two controls, rotten meat at 33 °C, or fresh meat supplemented with blood at 25 °C. The preference is assessed by counting the number of larvae or eggs laid in each option for each replicate. Comparing the observed results to a random distribution allowed for the estimation of the statistical significance of the preference. The results indicated that L. cuprina larvae have a strong preference for the rotten substrate at 25 °C. Conversely, oviposition-site preference by females was more varied for the meat type. This methodology can be adapted to test the preference of other insect species of similar size. Other questions can also be explored by using alternative conditions.

Palliative care interventions for patients with head and neck cancer: protocol for a scoping review.

INTRODUCTION: A head and neck cancer (HNC) diagnosis significantly impacts a patient's quality of life (QOL). Palliative care potentially improves their QOL. We will conduct a scoping review to identify existing knowledge about palliative care interventions for patients with HNC. METHODS AND ANALYSIS: This scoping review was designed in accordance with the JBI Manual for Evidence Synthesis: Scoping Reviews and will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Our eligibility criteria follow the Population, Intervention, Comparison or Control, Outcomes and Study characteristics framework. The population is adult patients with locally advanced, metastatic, unresectable and/or recurrent HNC. We include peer-reviewed journal articles and articles in the press, in English, reporting on palliative care interventions with at least two of the eight National Consensus Project on Clinical Practice Guidelines for Quality Palliative Care domains; studies with and without comparators will be included. The outcomes are patient QOL (primary) and symptom severity, patients' satisfaction with care, patients' mood, advance care planning and place of death (secondary). We developed a search strategy across ten databases, to be searched from the inception to 11 September 2023: Medline ALL (Medline and EPub Ahead of Print and In-Process, In-Data-Review & Other Non-Indexed Citations), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase Classic+Embase, Emcare and PsycINFO all from the OvidSP platform; CINAHL from EBSCOhost, Scopus from Elsevier, Web of Science from Clarivate and Global Index Medicus from WHO. We will extract data using a piloted data form and analyse the data through descriptive statistics and thematic analysis. ETHICS AND DISSEMINATION: Ethics approval is not needed for a scoping review. We will disseminate the findings to healthcare providers and policy-makers by publishing the results in a scientific journal.

Delivering Palliative and Supportive Care for Older Adults with Cancer: Interactions between Palliative Medicine and Geriatrics.

The world's population is aging rapidly, with projections indicating that by 2050 one in six people will be aged ≥65 years. As a result, the number of cancer cases in older people is expected to increase significantly. Palliative care is an essential component of cancer care with a direct impact on quality of life. However, older adults with cancer often suffer from multiple comorbidities, cognitive impairment, and frailty, posing unique challenges in the delivery of palliative care. The complex healthcare needs of older patients with cancer therefore require a comprehensive assessment, including a geriatric evaluation. Collaboration between geriatrics and palliative care can offer a solution to the challenges faced by older people with cancer, since this is a population with overlapping concerns for both disciplines. This review highlights the importance of palliative care for older adults with cancer and the benefits of a multidisciplinary approach. It also addresses the coordination of palliative care and geriatrics for specific symptom management and decision making.

Biomaterials Based on Organic Polymers and Layered Double Hydroxides Nanocomposites: Drug Delivery and Tissue Engineering.

The development of biomaterials has a substantial role in pharmaceutical and medical strategies for the enhancement of life quality. This review work focused on versatile biomaterials based on nanocomposites comprising organic polymers and a class of layered inorganic nanoparticles, aiming for drug delivery (oral, transdermal, and ocular delivery) and tissue engineering (skin and bone therapies). Layered double hydroxides (LDHs) are 2D nanomaterials that can intercalate anionic bioactive species between the layers. The layers can hold metal cations that confer intrinsic biological activity to LDHs as well as biocompatibility. The intercalation of bioactive species between the layers allows the formation of drug delivery systems with elevated loading capacity and modified release profiles promoted by ion exchange and/or solubilization. The capacity of tissue integration, antigenicity, and stimulation of collagen formation, among other beneficial characteristics of LDH, have been observed by in vivo assays. The association between the properties of biocompatible polymers and LDH-drug nanohybrids produces multifunctional nanocomposites compatible with living matter. Such nanocomposites are stimuli-responsive, show appropriate mechanical properties, and can be prepared by creative methods that allow a fine-tuning of drug release. They are processed in the end form of films, beads, gels, monoliths etc., to reach orientated therapeutic applications. Several studies attest to the higher performance of polymer/LDH-drug nanocomposite compared to the LDH-drug hybrid or the free drug.

Reproductive Desire in Women Living with HIV/AIDS with Serodiscordant Partners.

OBJECTIVE: To estimate the prevalence and factors associated with reproductive desire in a sample of women living with HIV/AIDS (WLHA) with serodiscordant partners. STUDY DESIGN: Between September 2015 and August 2016, a cross-sectional study was conducted among 110 WLHA from HIV/AIDS treatment services and non-governmental organizations. An interview was conducted using a structured questionnaire to collect sociodemographic data, reproductive desire, and potential predictor variables. Poisson regression was used to analyze the factors associated with reproductive desire in the sample. RESULTS: The prevalence of reproductive desire was 32.7% (95% Confidence Interval: % CI: 24.7-42.0%). In regression analysis, we observed an association between reproductive desire and the following variables: age < 30 years; relationship time < 2 years; reproductive desire for the partner; and absence of children. CONCLUSIONS: The prevalence of reproductive desire in the investigated sample was relatively high. Young age and reproductive desire for the partner were the main associated factors.

Anti-Inflammatory and Analgesic Evaluation of a Phytochemical Intercalated into Layered Double Hydroxide.

Coumaric acid (CouH), an antioxidant molecule assimilated by food consumption, was intercalated into layered double hydroxide (LDH) nanocarrier, having zinc and aluminium ions in the layers (LDH-Cou), to evaluate its pharmacological activity through in vitro and in vivo assays in mice. Therefore, the following tests were performed: coumarate delivery in saline solution, fibroblasts' cell viability using neutral red, peritonitis induced by carrageenan, formalin test, acetic-acid-induced writhing, and tail-flick assay, for the non-intercalated CouH and the intercalated LDH-Cou system. Furthermore, different pharmacological pathways were also investigated to evaluate their possible anti-inflammatory and antinociceptive mechanisms of action, in comparison to traditionally used agents (morphine, naloxone, caffeine, and indomethacin). The LDH-Cou drug delivery system showed more pronounced anti-inflammatory effect than CouH but not more than that evoked by the classic non-steroidal anti-inflammatory drug (NSAID) indomethacin. For the analgesic effect, according to the tail-flick test, the treatment with LDH-Cou expressively increased the analgesia duration (p < 0.001) by approximately 1.7−1.8 times compared to CouH or indomethacin. Thus, the results pointed out that the LDH-Cou system induced in vivo analgesic and anti-inflammatory activities and possibly uses similar mechanisms to that observed for classic NSAIDs, such as indomethacin.

Lactococcus lactis FNBPA+ (pValac:e6ag85a) Induces Cellular and Humoral Immune Responses After Oral Immunization of Mice.

The development of a new vaccine strategy against tuberculosis is urgently needed and has been greatly encouraged by the scientific community worldwide. In this work, we constructed a lactococcal DNA vaccine based on the fusion of two Mycobacterium tuberculosis antigens, ESAT-6 and Ag85A, and examined its immunogenicity. The coding sequences of the ESAT-6 and Ag85A genes were fused and cloned into the eukaryotic expression pValac vector, and the functionality of the vector was confirmed in vitro. Then, L. lactis FnBPA+ (pValac:e6ag85a) was obtained and used for oral immunization of mice. This strain induced significant increases in IFN-γ, TNF-α, and IL-17 cytokines in stimulated splenocyte cultures, and significant production of antigen-specific sIgA was observed in the colonic tissues of immunized mice. We demonstrated that L. lactis FnBPA+ (pValac:e6ag85a) generated a cellular and humoral immune response after oral immunization of mice. The strategy developed in this work may represent an interesting DNA mucosal vaccine candidate against tuberculosis, using the fusion of two highly immunogenic antigens delivered by safe lactic acid bacteria.

Recombinant Lactococcus lactis Carrying IL-4 and IL-10 Coding Vectors Protects against Type 1 Diabetes in NOD Mice and Attenuates Insulitis in the STZ-Induced Model.

Type 1 diabetes (T1D) is an autoimmune disease that culminates in beta cell destruction in the pancreas and, subsequently, deficiency in insulin production. Cytokines play a crucial role in the development of diabetes, orchestrating the recruitment and action of immune cells, to not only destroy insulin-producing cells but also preserve them. Therefore, the aim of this study was to investigate the effect of orally administered Lactococcus lactis MG1363 FnBPA+ strains carrying plasmids encoding IL-4 and IL-10 in the streptozotocin- (STZ-) induced diabetes model and in nonobese diabetic (NOD) mice. The STZ-induced mice that were treated with combined bacterial strains carrying plasmids encoding IL-4 and IL-10 showed lower incidence of diabetes and more preserved pancreatic islets than the mice that received the individual bacterial strains. Combined administration of L. lactis MG1363 FnBPA+ (pValac::dts::IL-4) and L. lactis MG1363 FnBPA+ (pValac::IL-10) resulted in protection against diabetes in NOD mice. It was shown that the combined treatment with recombinant bacterial by oral route prevented hyperglycemia and reduced the pancreatic islets-destruction in NOD mice. In addition, increased levels of IL-4 and IL-10 in serum and pancreatic tissue revealed a systemic effect of the treatment and also favored an anti-inflammatory microenvironment. Reduced concentrations of IL-12 in pancreas were essential to the regulation of inflammation, resulting in no incidence of diabetes in treated NOD mice. Normal levels of intestinal sIgA after long-term treatment with the L. lactis strains carrying plasmids encoding IL-4 and IL-10 indicate the development of oral tolerance and corroborate the use of this potent tool of mucosal delivery. For the first time, L. lactis MG1363 FnBPA+ strains carrying eukaryotic expression vectors encoding IL-4 and IL-10 are tested in STZ-induced and NOD mouse models. Therefore, our study demonstrates this innovative strategy provides immunomodulatory potential for further investigations in T1D and other autoimmune diseases.

Evaluation of a collagen matrix in a mandible defect in rats submitted to the use of bisphosphonates.

PURPOSE: To assess the effect of a collagen matrix (Mucograft®) on the inflammatory process in a semi-critical experimental defect model in rats treated with bisphosphonates. METHODS: Eighteen Wistar rats were randomly divided into three groups: saline (CG), alendronate (ALD) 5mg/kg (AG) or zoledronic acid (ZA) 0.2mg/kg (ZG). ALD was administered orally for 10 weeks and ZA was administered intravascularly on days 0, 7 and 14 and 49. On day 42, a 2mm defect was created and filled with Mucograft® collagen matrix. The contralateral side was filled with a clot (control side). The animals were euthanized 70 days after the beginning of the experiment and the hemimandibles were radiographically and histologically (counting of empty osteocyte lacunae (%), apoptotic (%) and total osteoclasts, neutrophil and mononuclear inflammatory cells) analyzed. The variables were submitted to ANOVA/Bonferroni and t test (parametric data) (p <0.05, GraphPad Prism 5.0). RESULTS: Significant bone repair occurred in the groups treated with Mucograft®. High number of total inflammatory cells and neutrophils cells were showed in AG (p=0.026 and p=0.035) and AZ groups (p=0.005, p=0.034) on the control sides associated with delayed bone repair and the presence of devitalized bone tissue in AG and ZG on the Mucograft® side. CONCLUSION: Mucograft® collagen matrix attenuated the inflammatory process in a mandible defect in rats submitted to the use of bisphosphonates (AG and ZG).

Molecular basis of resistance to organophosphate insecticides in the New World screw-worm fly.

BACKGROUND: The emergence of insecticide resistance is a fast-paced example of the evolutionary process of natural selection. In this study, we investigated the molecular basis of resistance in the myiasis-causing fly Cochliomyia hominivorax (Diptera: Calliphoridae) to dimethyl-organophosphate (OP) insecticides. METHODS: By sequencing the RNA from surviving larvae treated with dimethyl-OP (resistant condition) and non-treated larvae (control condition), we identified genes displaying condition-specific polymorphisms, as well as those differentially expressed. RESULTS: Both analyses revealed that resistant individuals have altered expression and allele-specific expression of genes involved in proteolysis (specifically serine-endopeptidase), olfactory perception and cuticle metabolism, among others. We also confirmed that resistant individuals carry almost invariably the Trp251Ser mutation in the esterase E3, known to confer OP and Pyrethroid resistance. Interestingly, genes involved in metabolic and detoxifying processes (notably cytochrome P450s) were found under-expressed in resistant individuals. An exception to this were esterases, which were found up-regulated. CONCLUSIONS: These observations suggest that reduced penetration and aversion to dimethyl-OP contaminated food may be important complementary strategies of resistant individuals. The specific genes and processes found are an important starting point for future functional studies. Their role in insecticide resistance merits consideration to better the current pest management strategies.

Mycobacterial Hsp65 antigen delivered by invasive Lactococcus lactis reduces intestinal inflammation and fibrosis in TNBS-induced chronic colitis model.

Intestinal fibrosis associated with Crohn's disease (CD), which a common and serious complication of inflammatory bowel diseases. In this context, heat shock proteins (HSPs) might serve as an alternative treatment because these antigens play important roles in the regulation of effector T cells. We thus evaluated the anti-inflammatory and antifibrotic capacities of an invasive and Hsp65-producing strain-Lactococcus lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65)-in chronic intestinal inflammation to assess its potential as an alternative therapeutic strategy against fibrotic CD. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in BALB/c mice, and the mice were treated orally with L. lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) via intragastric gavage. The oral administration of this strain significantly attenuated the severity of inflammation and intestinal fibrosis in mice (p < 0.05). These results are mainly justified by reductions in the levels of the pro-fibrotic cytokines IL-13 and TGF-ß and increases in the concentration of the regulatory cytokine IL-10. The L. lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) strain contributed to reductions in the severity of inflammatory damage in chronic experimental CD, and these findings confirm the effectiveness of this new antifibrotic strategy based on the delivery of therapeutic proteins to inside cells of the host intestinal mucosa.

Attenuation of intestinal inflammation in IL-10 deficient mice by a plasmid carrying Lactococcus lactis strain.

BACKGROUND: Inflammatory bowel diseases (IBD) are intestinal disorders characterized by inflammation in the gastrointestinal tract (GIT) and to date, no efficient treatments exist. Interleukin-10 (IL-10), one of the most important anti-inflammatory cytokines of the immune response, has been under study due to its potential for IBD therapy; however, systemic treatments lead to undesirable side effects and oral administration is limited due to its quick degradation. To avoid these bottlenecks, we previously engineered an invasive Lactococcus lactis (L. lactis) strain capable of delivering, directly to host cells, a eukaryotic DNA expression vector coding for IL-10 of Mus musculus (pValac:il-10) that diminished inflammation in two induced mouse models of intestinal inflammation. Thus, the aim of this study was to analyze its therapeutic effect in the IL-10-deficient mouse model (IL-10-/-) that spontaneously and gradually develops an inflammation that modifies the immune system and resembles Crohn's disease (CD) in humans, and evaluate if it would also diminish and/or prevent the onset of this disease. RESULTS: Oral administration of L. lactis MG1363 FnBPA+ (pValac:il-10) to IL-10-/- mice not only led to IL-10 production by these, but consequently also diminished the severe development of the disease, with animals showing lower macroscopic scores and histological damages, increased IL-10 levels and tendency to lower pro-inflammatory cytokine levels. CONCLUSIONS: The results of this study, together with the previously published ones using this DNA delivery-based strategy, show that it is capable of creating and maintaining an anti-inflammatory environment in the GIT and thus effectively diminish the onset of inflammation in various mouse models.

Evolution of diagnostic criteria for acute kidney injury in patients with decompensated cirrhosis: A prospective study in a tertiary university hospital.

BACKGROUND: Recently, changes in acute kidney injury (AKI) diagnostic criteria have been proposed (ICA-AKI criteria). However, in Brazil there is a paucity of data and analyses that evaluate AKI in patients with cirrhosis and determine the impact of the implemented AKI criteria changes. Therefore, this study sought to evaluate the incidence of AKI in patients with cirrhosis; to evaluate the agreement between traditional and ICA-AKI criteria; and to assess its clinical and laboratory characteristics, etiologies, risk factors and outcomes. METHODS: This is a prospective cohort study in hospitalized patients with cirrhosis and acute decompensation. The total number of hospitalizations was evaluated using the PWP statistical model for recurring events; P values<0.05 were considered significant. RESULTS: A total of 154 admissions of 75 patients were included in the study. Among the hospitalizations, 89 (57.79%) met the ICA-AKI criteria. There was substantial agreement between both AKI classifications (Kappa 0.7293). The main etiology of AKI was pre-renal (59.55%), followed by renal (26.96%) and hepatorenal syndrome (10.11%). A multivariate analysis uncovered risk factors for ICA-AKI, including the MELD score (P=0.0162, RR:1.055, 95% CI:1.010-1.101) and the use of furosemide (P=0.001,RR:2.360, 95% CI:1.417-3.931). A univariate analysis found an association between in-hospital mortality and serum creatinine (sCr)≥1.5mg/dL(P=0.0373), MELD (P=0.0296), bilirubin (P=0.0064), and infection (P=0.0045), while in the multivariate analysis, the bilirubin levels (P=0.0030, RR:1.077, 95% CI: 1.025-1.130) and the presence of shock (P=0.0002, RR:8.511, 95% CI: 2.746-26.377) were associated with in-hospital mortality. Among the hospitalizations with AKI, death was significantly associated with non-response to treatment and dialysis. Initial stage 1A-AKI had lower in-hospital mortality than stage 1B-AKI. CONCLUSIONS: AKI incidence was high in this cohort of patients with decompensated cirrhosis, and substantial agreement between AKI definitions was observed. In-hospital mortality was associated with worse liver function, AKI, infection and the presence of shock. Also, sCr>1,5mg/dL remained an important prognostic factor.

Evaluation of a collagen matrix in a mandible defect in rats submitted to the use of bisphosphonates

Abstract Purpose: To assess the effect of a collagen matrix (Mucograft®) on the inflammatory process in a semi-critical experimental defect model in rats treated with bisphosphonates. Methods: Eighteen Wistar rats were randomly divided into three groups: saline (CG), alendronate (ALD) 5mg/kg (AG) or zoledronic acid (ZA) 0.2mg/kg (ZG). ALD was administered orally for 10 weeks and ZA was administered intravascularly on days 0, 7 and 14 and 49. On day 42, a 2mm defect was created and filled with Mucograft® collagen matrix. The contralateral side was filled with a clot (control side). The animals were euthanized 70 days after the beginning of the experiment and the hemimandibles were radiographically and histologically (counting of empty osteocyte lacunae (%), apoptotic (%) and total osteoclasts, neutrophil and mononuclear inflammatory cells) analyzed. The variables were submitted to ANOVA/Bonferroni and t test (parametric data) (p <0.05, GraphPad Prism 5.0). Results: Significant bone repair occurred in the groups treated with Mucograft®. High number of total inflammatory cells and neutrophils cells were showed in AG (p=0.026 and p=0.035) and AZ groups (p=0.005, p=0.034) on the control sides associated with delayed bone repair and the presence of devitalized bone tissue in AG and ZG on the Mucograft® side. Conclusion: Mucograft® collagen matrix attenuated the inflammatory process in a mandible defect in rats submitted to the use of bisphosphonates (AG and ZG).

Epidemiology of hepatitis B virus infection in people living in poverty in the central-west region of Brazil.

BACKGROUND: People living in poverty (PLP) are highly vulnerable to hepatitis B virus (HBV) infection. This study aimed to investigate the epidemiology of HBV infection in PLP in the metropolitan region of Goiânia, Goiás State, in the Central-West Region of Brazil. METHODS: A cross-sectional study was conducted from August to December 2016 in adults aged ≥12 years living in poverty. The following serological markers for HBV were investigated: hepatitis B surface antigen (HBsAg), antibody to HBV core antigen (total anti-HBc), IgM anti-HBc, and hepatitis B surface antibody (anti-HBs), which were detected by enzyme-linked immunosorbent assay (ELISA). Poisson regression analysis with robust variance was performed to verify the factors associated with HBV exposure. RESULTS: The study included 378 participants. The overall prevalence rate of HBV (any viral marker) was 9.8% (95% confidence interval [CI], 7.2-13.2). The prevalence rate of HBsAg in combination with total anti-HBc was 0.8% (95% CI, 0.3-2.4), total anti-HBc in combination with anti-HBs was 7.7% (95% CI, 5.4-10.9), and total anti-HBc alone was 1.3% (95% CI, 0.5-3.0) in the population. Furthermore, isolated positivity for anti-HBs was identified in only 25.4% (95% CI, 21.3-30.0) of the participants. Multiple regression analysis revealed that age (adjusted prevalence ratio [APR], 1.04; 95% CI, 1.01-1.07), female sex (APR, 2.18; 95% CI, 1.01-4.73), sexual intercourse under the influence of alcohol (APR, 2.49; 95% CI, 1.36-7.06), and exposure to Treponema pallidum (APR, 3.10; 95% CI, 1.36-7.06) were associated with HBV exposure. CONCLUSION: There was a high prevalence of HBV exposure in PLP in the Central-West Region of Brazil, indicating significant viral spread of the infection. Additionally, there was low serological evidence of immunisation against hepatitis B, indicating that a large proportion of the participants in this study are susceptible to the infection. The results support the need for public health policies that facilitate access to the existing healthcare services in hard-to-reach groups with special regard to immunisation programmes against hepatitis B.

HIV infection, high-risk behaviors and substance use in homeless men sheltered in therapeutic communities in Central Brazil.

Homeless men present high vulnerability to HIV infection, mainly due to sexual risk behaviors and substance use. The objective was to estimate the prevalence of HIV infection, risk behaviors and substance use in homeless men. A cross-sectional study was conducted in 481 homeless men recruited in four therapeutic communities in the Goiás State, Central Brazil. All were interviewed about sociodemographic characteristics, substance use, and risk behaviors. Furthermore, all were tested for HIV. Poisson regression was used to verify factors associated with HIV infection. HIV prevalence was 1.24% (95.0% CI: 0.57 to 2.69%). Previous HIV testing (adjusted prevalence ratio [APR]: 10.0; 95.0% CI: 1.86-55.8) and years of education (APR: 0.76; 95.0% CI: 0.60-0.97) were factors associated with HIV infection. Participants had high rates of hazardous alcohol use and illicit drug use. The prevalence of HIV infection among homeless men was higher than that found in the Brazilian male population and we identified a high rate of risk behaviors for HIV among the homeless men investigated. Thus, it is necessary to expand HIV prevention measures in Brazil, such as health education, condom availability, regular HIV testing and increased testing coverage in this population, and treatment for alcohol and/or illicit drug dependence/abuse.

Lactococcus lactis carrying the pValac eukaryotic expression vector coding for IL-4 reduces chemically-induced intestinal inflammation by increasing the levels of IL-10-producing regulatory cells.

BACKGROUND: Inflammatory bowel diseases are characterized by chronic intestinal inflammation that leads to severe destruction of the intestinal mucosa. Therefore, the understanding of their aetiology as well as the development of new medicines is an important step for the treatment of such diseases. Consequently, the development of Lactococcus lactis strains capable of delivering a eukaryotic expression vector encoding the interleukin 4 (IL-4) of Mus musculus would represent a new strategy for the elaboration of a more effective alternative therapy against Crohn's disease. RESULTS: The murine IL-4 ORF was cloned into the eukaryotic expression vector pValac::dts. The resulting plasmid-pValac::dts::IL-4-was transfected into CHO cells so that its functionality could be evaluated in vitro. With fluorescent confocal microscopy, flow cytometry and ELISA, it was observed that pValac::dts::IL-4-transfected cells produced IL-4, while non-transfected cells and cells transfected with the empty vector did not. Then, pValac::dts::IL-4 was inserted into L. lactis MG1363 FnBPA(+) in order to evaluate the therapeutic potential of the recombinant strain against TNBS-induced colitis. Intragastric administration of L. lactis MG1363 FnBPA(+) (pValac::dts::IL-4) was able to decrease the severity of colitis, with animals showing decreased levels of IL-12, IL-6 and MPO activity; and increased levels of IL-4 and IL-10. Finally, LP-isolated cells from mice administered TNBS were immunophenotyped so that the main IL-4 and IL-10 producers were identified. Mice administered the recombinant strain presented significantly higher percentages of F4/80(+)MHCII(+)Ly6C(-)IL-4(+), F4/80(+)MHCII(+)Ly6C(-)IL-10(+), F4/80(+)MHCII(+)Ly6C(-)CD206(+)CD124(+)IL-10(+) and CD4(+)Foxp3(+)IL10(+) cells compared to the other groups. CONCLUSIONS: This study shows that L. lactis MG1363 FnBPA(+) (pValac::dts::IL-4) is a good candidate to maintain the anti-inflammatory and proinflammatory balance in the gastrointestinal tract, increasing the levels of IL-10-secreting regulatory cells and, thus, demonstrating the effectiveness of this novel DNA delivery-based strategy.

Accessing the biocompatibility of layered double hydroxide by intramuscular implantation: histological and microcirculation evaluation.

Biocompatibility of layered double hydroxides (LDHs), also known as hydrotalcite-like materials or double metal hydroxides, was investigated by in vivo assays via intramuscular tablets implantation in rat abdominal wall. The tablets were composed by chloride ions intercalated into LDH of magnesium/aluminum (Mg2Al-Cl) and zinc/aluminum (Zn2Al-Cl). The antigenicity and tissue integration capacity of LDHs were assessed histologically after 7 and 28 days post-implantation. No fibrous capsule nearby the LDH was noticed for both materials as well any sign of inflammatory reactions. Sidestream Dark Field imaging, used to monitor in real time the microcirculation in tissues, revealed overall integrity of the microcirculatory network neighboring the tablets, with no blood flow obstruction, bleeding and/or increasing of leukocyte endothelial adhesion. After 28 days Mg2Al-Cl promoted multiple collagen invaginations (mostly collagen type-I) among its fragments while Zn2Al-Cl induced predominantly collagen type-III. This work supports previous results in the literature about LDHs compatibility with living matter, endorsing them as functional materials for biomedical applications.

Delivery system for mefenamic acid based on the nanocarrier layered double hydroxide: Physicochemical characterization and evaluation of anti-inflammatory and antinociceptive potential.

PURPOSE: The anionic form of the drug mefenamic acid intercalated into the nanocarrier layered double hydroxide (LDH-Mef) was evaluated by anti-inflammatory and antinociceptive assays. METHODS: The LDH-Mef material was characterized by a set of physicochemical techniques, which was supported by Density Functional Theory calculations. The pharmacological effects of LDH-Mef (40 wt% of drug) were evaluated by hemolytic, anti-inflammatory activity and antinociceptive assays. RESULTS: In vivo assays were conducted for the first time in order to assess the LDH-Mef potential. The hemolytic effects decreased for the intercalated Mef as demonstrated by the higher tolerated hemolytic concentration (1.83 mM) compared to mefenamic acid (MefH), 0.48 mM. Pretreatment of animals with MefH or LDH-Mef reduced carrageenan-, dextran sulfate- and PGE2-induced paw edema. MefH or LDH-Mef also decrease total leucocytes and neutrophil counts of the peritoneal cavity after inflammation induction with carrageenan. In the nociception model, oral pretreatment with LDH-Mef reduced mechanical hypernociception carrageenan-induced after 3-4h and also the number of writhings induced by acetic acid. CONCLUSIONS: This work shows the increase of the anti-inflammatory and antinociceptive potential of the drug confined into the LDH, as well as, its hemolytic effect.

Intra pulp chamber temperature variation caused by Nd: YAG and Diode LASER irradiation / Variação da temperatura intracâmara pulpar provocada pela irradiação com laser de Diodo e Nd: YAG

A irradiação com LASER de Neodímio (Nd:YAG) e de Diodo sobre sistemas adesivos pode aumentar a resistência de união em dentina, no entanto a existe a preocupação com a variação de temperatura intracâmara pulpar. O objetivo deste trabalho foi avaliar a variação da temperatura intracâmara pulpar após a aplicação dos sistemas adesivos e subsequente a irradiação com LASER de diodo e Nd:YAG. Material e Métodos: Este estudo apresentou um desenho experimental fatorial com dois fatores: LASER em dois níveis (Diodo [D] e Nd:YAG [N]) e sistema adesivo em quatro níveis (Adper™ Scotchbond™ Multi-Purpose [MP], Adper™ SingleBond 2 [SB], Clearfil™ SE Bond [CSE] e Adper™ Easy One [EO]). A variável de resposta quantitativa foi a variação da temperatura (∆t) em ºC .Utilizou-se 40 dentes bovinos, separados em 8 grupos (n=5), a superfície vestibular foi desgastada até 1 mm de espessura. Depois da aplicação de cada sistema adesivo, mas previamente a fotopolimerização, os espécimes eram irradiados com LASER de diodo e Nd:YAG com parâmetro padronizados. A ∆t foi obtida com um termopar inserido intracâmara pulpar. Os valores obtidos foram submetidos ao teste ANOVA a 2 critérios seguido de Tukey para comparações individuais(p<0,05). Resultados: A média e o desvio padrão da ∆t obtidos foram: N-MP: 12.60 (± 2.51), N-SB: 10.40 (± 5.03), N-CSE: 11.80 (± 5.12) e N-EO: 10.20 (± 2.39), D-MP: 4.4 (± 1.82), D-SB: 5.20 (± 1.54), D-CSE: 4.60 (± 1.14), D-EO: 3.60 (± 1.52). Conclusão: O tipo de sistema adesivo não foi significante no aquecimento gerado pela irradiação com LASER, mas o LASER de Nd:YAG pode fornecer um potencial maior para causar danos a pulpar...

Neodymium (Nd:YAG) and Diode LASER irradiation on adhesive systems canincrease bond strength to dentin, however, concerns about the temperature variation inside pulp chamber still remain. The aim of this study was to evaluate the intra pulp chamber temperature variation caused by irradiation with Nd:YAG or Diode LASER on different adhesive systems. Material and Methods: This study presented experimental design with two factors: LASER on two levels (Diode [D] and Nd:YAG [N]) and adhesive system on four levels (Adper™ Scotchbond™ Multi-Purpose [MP], Adper™ SingleBond 2 [SB], Clearfil™ SE Bond [CSE] and Adper™ Easy One [EO]). The quantitative response variable was the temperature variation (∆t) in ºC. Forty bovine teeth, distributed into 8 groups (n = 5), had the buccal surface flattened up to1 mm thickness of dentin. After the application of each adhesive system, but previously to the light curing, specimens were irradiated with Nd:YAG or Diode LASER with standardized parameters. The ∆t was obtained through a thermocouple inserted into pulp chamber. The values of ∆t were submitted to two-way ANOVA, followed by Tukey (p < 0.05) for individual comparisons. Results: The means (± standard deviation) of ∆t were: N-MP: 12.60 (± 2.51), N-SB: 10.40 (± 5.03), N-CSE: 11.80 (± 5.12) and N-EO: 10.20 (± 2.39), D-MP: 4.4 (± 1.82), D-SB: 5.20 (± 1.54), D-CSE: 4.60 (± 1.14), D-EO: 3.60 (± 1.52). Conclusion: The type of adhesive system was not significant in temperature changes generated by LASER irradiation, but Nd:YAG LASER may provide a higher potential to cause pulp damage...