Inflammatory cells proliferate in the choroid and retina without choroidal thickness change in early Type 1 diabetes.

Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy (DR). Choroidal inflammatory changes in diabetes have been reported and in vivo choroidal thickness (CT) has been searched as a marker of retinopathy with contradictory results. We aimed to investigate the early stages in the retina and choroid in an animal model of Type 1 diabetes. Type 1 diabetes was induced in male Wistar rats via a single i.p. streptozotocin injection. At 8 weeks after disease onset, CT, choroidal vascular density, VEGF and VEGFR2 expression, microglial cell and pericyte distribution were evaluated. Diabetic rats showed no significant change in CT and choroidal vascular density. A widened pericyte-free gap between the retinal pigment epithelium and the choroid was observed in diabetic rats. The immunoreactivity of VEGFR2 was decreased in the retina of diabetic rats, despite no statistically significant difference in the immunoreactivity of VEGF. The density of microglial cells significantly increased in the choroid and retina of diabetic rats. Reactive microglial cells were found to be more abundant in the choroid of diabetic rats. Evidences of the interconnection between the superficial, intermediate, and deep plexuses of the retina were also observed. At early stages, Type 1 diabetes does not affect choroidal thickness and choroidal vascular density. Proliferation and reactivity of microglial cells occurs in the choroidal stroma and the retina. The expression of VEGFR2 decreases in the retina.

Non-specific effects and clusters of women with painful TMD responders and non-responders to LLLT: double-blind randomized clinical trial.

The aim was to analyze the non-specific effects (placebo, spontaneous remission, and regression to the mean) of the low-level laser therapy (LLLT) in women with myofascial pain (painful temporomandibular disorder (TMD)), as well as to differentiate between responders and non-responder clusters to active and placebo LLLT according to the anxiety levels, salivary cortisol, use of oral contraceptives, and premenstrual period. Sixty-four women diagnosed with myofascial pain (Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD)) were included, divided into laser (n = 20), placebo group (n = 21), and 23 controls (without treatment (WT)). The LLLT applied was 780 nm, masseter and temporal = 5 J/cm2 (20 mW-0.5 W/cm2), and TMJ area = 7.5 J/cm2 (30 mW-0.8 W/cm2), eight sessions, twice a week. The pain intensity (visual analogue scale (VAS)), anxiety (Beck Anxiety Inventory), salivary cortisol, and menstrual cycle's data at the baseline, T1-T8, and 30 days after LLLT (follow-up) were evaluated. The laser group showed 80% of pain reduction, placebo 85%, and WT 43% in T8. Women with severe anxiety and at the premenstrual period did not reduce pain with any LLLT. Active and placebo LLLT had similar effectiveness during the treatment period; however, women with moderate anxiety, cortisol levels above 10 ng/ml, and without contraceptive use maintain analgesia longer with active LLLT than placebo (follow-up 30 days). Women with low levels of anxiety, salivary cortisol below 10 ng/ml, and with contraceptive use showed the higher pain reduction. The analgesia promoted by LLLT in women with myofascial pain is a result of non-specific effects during the treatment period, although active LLLT is more effective in maintaining the analgesia after treatment (30 days) for the cluster of women with moderate anxiety, salivary cortisol above 10 ng/ml, and without contraceptive use.

Micro-CT and FE-SEM enamel analyses of calcium-based agent application after bleaching.

OBJECTIVES: The objective of the present study is to evaluate the effects of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on bleached enamel. MATERIALS AND METHODS: A bleaching agent (35% hydrogen peroxide) was applied, 4 × 8 min on premolar teeth (n = 8). A CPP-ACP paste was applied for 7 days. Prior and post-treatment, microtomography images were obtained and 3D regions of interest (ROIs) were selected, from outer enamel, extending to 110.2-µm depth. CT parameters of structure: thickness (St.Th), separation (St.Sp), and fragmentation index (Fr.I.) were calculated for each (ROI). Data was submitted to paired t tests at a 95% confidence level. The samples were evaluated at 3000 to 100,000 magnification. Quantitative analysis of enamel mineral content was also determined by SEM EDX. RESULTS: There was a significant increase in structure thickness and calcium content. The phosphorus content increased after bleaching. There was also a decreased separation and fragmentation index on the outer enamel to a depth of 56.2 µm (p < 0.05). There were no changes at 110.2-µm depth for the bleaching CPP-ACP association. A covering layer and decreased spaces between the hydroxyapatite crystals appeared around the enamel prisms, 7 days after the CPP-ACP application. CONCLUSIONS: The application of a CPP-ACP provides a compact structure on the enamel's outer surface, for 7 days, due to calcium deposition. CT parameters seem to be a useful tool for mineralizing and remineralizing future studies. CLINICAL RELEVANCE: CPP-ACP neutralizes any adverse effects on enamel surface when applied during a week after bleaching and minimizes any side effects of the bleaching treatment due to a more compact structure.

Mutation rates in 21 autosomal short tandem repeat loci in a population from Goiás, Brazil.

The appearance of new mutations in polymorphic markers plays a central role in a range of genetic applications, including dating phylogenetic events, informing disease studies, and evaluating forensic evidence. The present study estimated the mutation rates of 21 autosomal STR loci in a population from Central Brazil. We studied 15 046 paternity cases from Goiás, Brazil from August 2012 to February 2015. We identified 262 mutations in the 21 loci. The loci that presented more mutations were FGA and D18S51, with a total of 46 and 28 mutations, respectively. The results showed mutational rates ranging from 1.7 × 10-5 to 7.6 × 10-4 mutations per site/region and the overall mutational rate was 2.1 × 10-4 ; these values were within the expected values for the STR markers. The most common type of mutation was one-step mutation, which totaled 96.2%. We found a higher rate of mutations of paternal origin (67.6%) than of mutations of maternal origin. The occurrence of mutations in STRs has important consequences for human identification, including the definition of criteria for exclusion in paternity testing and interpretation of genetic profiles in criminal cases.

Effectiveness of low-level laser therapy on pain intensity, pressure pain threshold, and SF-MPQ indexes of women with myofascial pain.

Women with temporomandibular disorders (TMD) frequently report pain areas in body regions. This process is associated with central sensitization phenomena, present in chronic pain. The low-level laser therapy (LLLT) has been reported as a therapeutic option for the painful TMD treatment. The aim of this study was to analyze the effect of LLLT on pain intensity (visual analogue scale, VAS), pain sensitivity in orofacial and corporal points (pressure pain threshold, PPT), and on Short Form-McGill Pain Questionnaire (SF-MPQ) indexes of women with myofascial pain (subtype of muscle TMD). Ninety-one women (18-60 years) were included in the study, among which 61 were diagnosed with myofascial pain (Research Diagnostic Criteria for Temporomandibular Disorder-Ia and Ib) and were divided into laser (n = 31) and placebo group (n = 30), and 30 were controls. The LLLT was applied at pre-established points, twice a week, eight sessions (780 nm; masseter and anterior temporal = 5 J/cm2, 20 mW, 10 s; TMJ area = 7.5 J/cm2, 30 mW, 10 s). Pain intensity, pain sensitivity, and the SF-MPQ indexes were measured at the baseline, during laser sessions, and 30 days after treatment. For intra-group comparisons, the Friedman test was performed, and for inter-group, the Mann-Whitney test. Increased pain sensitivity was found in women with myofascial pain when compared to controls (p < 0.05). There was a reduction in pain intensity for both groups after LLLT. The LLLT did not change the PPT for any group (p > 0.05). Active laser and placebo reduced the indexes of sensory, total pain, and VAS, maintaining the results after 30 days; there was a reduction in the affective pain rating index for both groups, with no maintenance after 30 days for placebo, and the present pain intensity decreased in the laser group and did not change in the placebo after LLLT. In conclusion, the LLLT active or placebo are effective in reducing the overall subjective perception of myofascial pain (VAS and SF-MPQ indexes); however, they have no effectiveness in reducing the pain sensitivity in orofacial and corporal points (PPT increase).

Zirconia-Reinforced Lithium Silicate Ceramic - A 2-Year Follow-up of a Clinical Experience with Anterior Crowns.

The aim of this manuscript is to describe 2-year follow-up of a clinical experience with a zirconia-reinforced lithium silicate ceramic for an anterior rehabilitation with single metal-free crowns. The maxillary-central incisor teeth crowns were made by zirconium-reinforced lithium silicate and covered with porcelain were obtained with a digital impression with the intra-oral scanner of the CEREC system as a basis for virtual design, as well as a laminate for the left lateral maxillary incisor, based on a "double scanning" technique. Lithium silicate material seems to be a safe and satisfactory alternative for anterior crowns' rehabilitation.

[The mental health promotion of children and teenagers in vulnerability and social violence: the challenges for an intersectoral network]. / La promotion de la santé mentale des enfants et adolescents en situation de vulnérabilité et violence sociale : les défis pour un réseau intersectoriel.

This paper presents and discusses the results of an intervention research conducted in Ouro Preto, Brazil from August 2014 to March 2016. The main objective was to contribute to the development of an intersectoral and interdisciplinary network to face psychosocial vulnerabilities of children and teenagers, especially related to sexual violence and drug use. To achieve this, we identified the difficulties faced by the Sistema de Garantia de Direitos Humanos da Criança e do Adolescente (SGDHCA) implemented by the municipality which take care of this population. We also identified protective and promotion factors accomplished to empower them. The methodology used combines Deleuze and Guattari Cartography, Institutional Analysis and the Cross Training. This latter methodology was developed by a group of researchers of Douglas Institute, in Montreal, which we met through scientific co-operation with our laboratory. On account of the practical-theoric and co-participative activities with the professional network of Ouro Preto, we produced a detailed diagnosis of the SGDHCA and a document proposing short, medium and long-term strategies. As final result, we intend to help the local collective-the Forum Intersetorial da Infância e Juventude-to develop a work plan from the proposed actions. In this paper we will concentrate the potential of the methodology used by presenting outcome from two important moments of the research: the discussions of successful and unsuccessful cases that elucidate the network operation and the potential and difficulties arising from the Rotation Positional, important technical of the Cross Training.

Zirconia Rehabilitation Focused on the Emergence Profile: A Case Report.

The first choice for anterior rehabilitation has been metal-free materials due to their successful aesthetic results. However, the definitive clinical work accuracy may be affected by the lack of clinicians' expertise and familiarization with the latest techniques, as well as recurrent laboratory procedures. This manuscript presents a clinical experience with zirconia ceramic for anterior crowns and zirconia CAD/CAM abutments, including both clinical and laboratory steps after the implant installation. The 'emergence profile' and the 'double scanning' techniques obtained by the waxing technique appear to be a very promising procedure for aesthetic improvement of the single-implant zirconia restoration in anterior teeth.

Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity.

Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB1 receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB1 receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity.

Effect of mushroom Agaricus blazei on immune response and development of experimental cerebral malaria.

BACKGROUND: Cerebral malaria (CM) is debilitating and sometimes fatal. Disease severity has been associated with poor treatment access, therapeutic complexity and drug resistance and, thus, alternative therapies are increasingly necessary. In this study, the effect of the administration of Agaricus blazei, a mushroom of Brazilian origin in a model of CM caused by Plasmodium berghei, strain ANKA, was investigated in mice. METHODS: C57BL/6 mice were pre-treated with aqueous extract or fractions of A. blazei, or chloroquine, infected with P. berghei ANKA and then followed by daily administration of A. blazei or chloroquine. Parasitaemia, body weight, survival and clinical signs of the disease were evaluated periodically. The concentration of pro-and anti-inflammatory cytokines, histopathology and in vitro analyses were performed. RESULTS: Mice treated with A. blazei aqueous extract or fraction C, that shows antioxidant activity, displayed lower parasitaemia, increased survival, reduced weight loss and protection against the development of CM. The administration of A. blazei resulted in reduced levels of TNF, IL-1ß and IL-6 production when compared to untreated P. berghei-infected mice. Agaricus blazei (aqueous extract or fraction C) treated infected mice displayed reduction of brain lesions. Although chloroquine treatment reduced parasitaemia, there was increased production of proinflammatory cytokines and damage in the CNS not observed with A. blazei treatment. Moreover, the in vitro pretreatment of infected erythrocytes followed by in vivo infection resulted in lower parasitaemia, increased survival, and little evidence of clinical signs of disease. CONCLUSIONS: This study strongly suggests that the administration of A. blazei (aqueous extract or fraction C) was effective in improving the consequences of CM in mice and may provide novel therapeutic strategies.

[Adherence to nutritional recommendations and sociodemographic variables in patients with diabetes mellitus]. / Adesão às recomendações nutricionais e variáveissociodemográficas em pacientes com diabetes mellitus.

OBJECTIVE: To determine if there is a relationship between adherence to nutritional recommendations and sociodemographic variables in Brazilian patients with type 2 diabetes mellitus. METHODS: Cross-sectional observational study using a stratified random sample of 423 individuals. The Food Frequency Questionnaire (FFQ) was used, and the Fisher's exact test was applied with 95% confidence interval (p<0.05). RESULTS: Of the 423 subjects, 66.7% were women, mean age of 62.4 years (SD = 11.8), 4.3 years of schooling on average (SD = 3.6) and family income of less than two minimum wages. There was association between the female gender and adherence to diet with adequate cholesterol content (OR: 2.03; CI: 1.23; 3.34), between four and more years of education and adherence to fractionation of meals (OR: 1 92 CI: 1.19; 3.10), and income of less than two minimum wages and adherence to diet with adequate cholesterol content (OR: 1.74; CI: 1.03, 2.95). CONCLUSION: Adherence to nutritional recommendations was associated with the female gender, more than four years of education and family income of less than two minimum wages.

Trypanosoma cruzi as an effective cancer antigen delivery vector.

One of the main challenges in cancer research is the development of vaccines that induce effective and long-lived protective immunity against tumors. Significant progress has been made in identifying members of the cancer testis antigen family as potential vaccine candidates. However, an ideal form for antigen delivery that induces robust and sustainable antigen-specific T-cell responses, and in particular of CD8(+) T lymphocytes, remains to be developed. Here we report the use of a recombinant nonpathogenic clone of Trypanosoma cruzi as a vaccine vector to induce vigorous and long-term T cell-mediated immunity. The rationale for using the highly attenuated T. cruzi clone was (i) the ability of the parasite to persist in host tissues and therefore to induce a long-term antigen-specific immune response; (ii) the existence of intrinsic parasite agonists for Toll-like receptors and consequent induction of highly polarized T helper cell type 1 responses; and (iii) the parasite replication in the host cell cytoplasm, leading to direct antigen presentation through the endogenous pathway and consequent induction of antigen-specific CD8(+) T cells. Importantly, we found that parasites expressing a cancer testis antigen (NY-ESO-1) were able to elicit human antigen-specific T-cell responses in vitro and solid protection against melanoma in a mouse model. Furthermore, in a therapeutic protocol, the parasites expressing NY-ESO-1 delayed the rate of tumor development in mice. We conclude that the T. cruzi vector is highly efficient in inducing T cell-mediated immunity and protection against cancer cells. More broadly, this strategy could be used to elicit a long-term T cell-mediated immunity and used for prophylaxis or therapy of chronic infectious diseases.

[Adherence to diabetes mellitus treatments in family health strategy units]. / Adesão ao tratamento em diabetes mellitus em unidades da Estratégia Saúde da Família.

This cross-sectional study aimed to analyze the adherence to drug and non-drug treatments in 17 Family Health Strategy units. A total of 423 patients with type 2 diabetes mellitus were selected through stratified random sampling in Family Health Strategy units of a city in the state of Minas Gerais, Brazil, in 2010. The results showed that the prevalence rate of adherence to drug therapy was higher than 60% in the 17 units investigated; in relation to physical activity, adherence was higher than 60% in 58.8% units; and for the diet plan, there was no adherence in 52.9% units. Therefore, we concluded that adherence to drug therapy in most units was high and the practice of physical activity was heterogeneous, and in relation to diet adherence, it was low in all units. We recommend strengthening of institutional guidelines and educational strategies, in line with SUS guidelines, so that, professionals may face the challenges imposed by the lack of adherence.

Ibuprofen-Immobilized Thin Films: A Novel Approach to Improve the Clearance of Protein-Bound Uremic Toxins.

Chronic kidney disease (CKD), a pressing global health issue, affects millions and leads to end-stage renal disease (ESRD). Hemodialysis (HD) is a crucial treatment for ESRD, yet its limited efficiency in removing protein-bound uremic toxins (PBUTs) results in high morbidity and mortality rates. A high affinity of pharmaceutical drugs for human serum albumin (HSA) can be leveraged to compete effectively with PBUTs for the same HSA binding sites, thereby enabling them to be capable of displacing these toxins. One such drug is ibuprofen (IBF), known for its very high affinity for HSA and sharing the same binding site as indoxyl sulfate (IS). This study explores the development of IBF-immobilized cellulose acetate-based (CA-based) thin films. The films were created by reacting CA with IBF-modified silica precursors at varying concentrations. The presence of IBF in CA/TEOS/APTES-IBF-3 and CA/TEOS-IBF-25 films, containing 3 and 25 wt % IBF, respectively, was confirmed through 1H NMR spectra. Competitive displacement binding assays indicated that while the incorporation of 3 wt % IBF showed no significant enhancement in IS displacement, the 25 wt % IBF film increased the dialyzed IS by 1.3 when normalized to non-IBF films. Furthermore, there was a 1.2-fold decrease in the total percentage of IS, and the free percentage of IS increased 1.3 to 3.0 times. Although direct systemic infusion of IBF in HD patients achieves a 2.4 times higher removal of IS, it is impractical due to the risks it poses to ESRD patients. The IBF-immobilized films offer the advantage of localized binding, thus eliminating the need for systemic exposure. This innovative approach lays a foundation for developing more efficient HD membranes, aiming to address the challenging issue of PBUT elimination and potentially enhance the quality of life and treatment outcomes for ESRD patients.

Validation of entrustable professional activities for use in neonatal care residency programs.

OBJECTIVE: Define and develop a set of entrustable professional activities (EPAs) to link clinical training and assessment of the hospital components of neonatal care in neonatology medical residency programs. METHODS: An exploratory study was conducted in two phases using a modified Delphi approach. In the first phase, a committee of five neonatology residency program coordinators drafted an initial set of EPAs based on the national matrix of competencies and on EPAs defined by international organizations. In the second phase, a group of neonatal care physicians and medical residents rated the indispensability and clarity of the EPAs and provided comments and suggestions. RESULTS: Seven EPAs were drafted by the coordinators´ committee (n = 5) and used in the content validation process with a group (n = 37) of neonatal care physicians and medical residents. In the first Delphi round, all EPAs reached a content validity index (CVI) above 0.8. The coordinators´ committee analyzed comments and suggestions and revised the EPAs. A second Delphi round with the revised EPAs was conducted to validate and all items maintained a CVI above 0.8 for indispensability and clarity. CONCLUSION: Seven entrustable professional activities were developed to assess residents in the hospital components of neonatal care medicine. These EPAs might contribute to implementing competency-based neonatology medical residency programs grounded in core professional activities.

Pfaffia paniculata Extract, a Potential Antimicrobial Agent against Candida spp., Pseudomonas aeruginosa, and Streptococcus mutans Biofilms.

The World Health Organization (WHO) has prioritized developing new drugs against specific bacteria and fungi, such as Enterobacteriaceae and Candida spp. While Pfaffia paniculata is commonly called the "cure-everything", its scientifically proven benefits are limited to anti-inflammatory and antioxidant actions. Therefore, this study aims to determine the spectrum of antimicrobial activity of Pfaffia paniculata and assess its cytotoxicity. Thus, broth microdilution test was conducted according to the CLSI M7-A9 and M27-A3 reference methods. After screening, microbial species with minimum inhibitory concentration (MIC) values were selected for biofilm tests. These tests evaluated biomass using the crystal violet (CV) test, metabolic activity using the MTT assay, and structural analysis via Scanning Electron Microscopy (SEM). Cytotoxicity was evaluated in human gingival fibroblasts (FMM-1). There were reductions of 29.4 and 42.7% in CV and MTT assays for Candida spp. biofilm. S. mutans and P. aeruginosa biofilms showed a decrease of 15.7 and 28.6%, respectively. Cell viability tests indicated 55.1, 56.9, and 65.5% of viability after contact with 1.93, 0.96, and 0.48 mg/mL of the extract, respectively. The P. paniculata extract showed antimicrobial action, displayed MIC values, and antibiofilm action on P. aeruginosa, S. mutans, and C. albicans. The cytotoxicity on the FMM-1 cell line was dose-dependent. Therefore, P. paniculata extract holds significant potential for developing new drugs.

[Quality of life in patients with diabetes using the Diabetes 39 (D-39) instrument]. / Qualidade de vida de pacientes com diabetes utilizando o instrumento diabetes 39 (D-39).

The purpose of this study is to investigate the specific quality of life of patients with diabetes mellitus. It is a cross-sectional study, which was conducted from August 2-28, 2012 in two basic health units, in the interior of São Paulo. A convenience sample, made up of 75 patients, 18 years old or older, both sexes, in a group of self-monitoring of blood glucose, was used. The Diabetes 39 (D-39) Instrument Evaluation, containing five dimensions: energy and mobility (15 items), diabetes control (12), anxiety and worry (4) social overload (5) and sexual behavior (3), was used. Quality of life proved to be highly affected in the items related to the social overload dimension, embarrassment for having diabetes, being called diabetic and diabetes interfering with family life. The elucidation of the assessed factors contributes to the planning of educational programs, insofar as they may hinder the achievement of metabolic control in patients with diabetes.

[Patients' knowledge of diabetes five years after the end of an educational program]. / Conhecimento de pacientes com diabetes sobre tratamento após cinco anos do término de um programa educativo.

We present a cross-sectional study that aims to describe the sociodemographic and clinical conditions of individuals with diabetes mellitus and to analyze their knowledge of treatment five years after the end of an educational program in which they took part. In 2010, 40 individuals who had participated in a diabetes educational program for 12 months in 2005 at a primary care service were interviewed. A form was used for data collection that included their knowledge of the notion, physiopathology, and treatment of the disease; exercise; nutrition; foot care; self-monitoring of capillary blood glucose at home; hypoglycemia; chronic complications; special situations; and family support. The results showed that the volunteers incorporated the information about the notion, physiopathology, and treatment of the disease; exercise; foot care; self-monitoring; care associated with hypoglycemia; chronic complications; and special situations. In contrast, nutrition and family support require further reinforcement. It is concluded that five years after the end of the educational program, the participants kept most of the information provided.

Adsorption- and Displacement-Based Approaches for the Removal of Protein-Bound Uremic Toxins.

End-stage renal disease (ESRD) patients rely on renal replacement therapies to survive. Hemodialysis (HD), the most widely applied treatment, is responsible for the removal of excess fluid and uremic toxins (UTs) from blood, particularly those with low molecular weight (MW < 500 Da). The development of high-flux membranes and more efficient treatment modes, such as hemodiafiltration, have resulted in improved removal rates of UTs in the middle molecular weight range. However, the concentrations of protein-bound uremic toxins (PBUTs) remain essentially untouched. Due to the high binding affinity to large proteins, such as albumin, PBUTs form large complexes (MW > 66 kDa) which are not removed during HD and their accumulation has been strongly associated with the increased morbidity and mortality of patients with ESRD. In this review, we describe adsorption- and displacement-based approaches currently being studied to enhance the removal of PBUTs. The development of mixed matrix membranes (MMMs) with selective adsorption properties, infusion of compounds capable of displacing UTs from their binding site on albumin, and competitive binding membranes show promising results, but the road to clinical application is still long, and further investigation is required.

Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin.

Diazinon (DZN) is an insecticide extensively used to control pests in crops and animals. However, its indicriminated use may lead to liver damage in animals and humans. This study aimed to evaluate the toxicity of DZN (25-150 µM) on human hepatoblastoma (HepG2) cells after 24 and 48 h of exposure and the role of its biotransformation on the toxicological potential. We also tested the protective effect of tetrahydrocurcumin (THC), an antioxidant agent, in the DZN-induced citotoxicity. DZN caused cytotoxicity in the HepG2 cells, inhibiting cell proliferation and reducing cell viability in a dose- and time-dependent manner. The pre-incubation of HepG2 cells with chemical inducers of cytochrome P450 monooxygenase 3-methylcholanthrene and phenobarbital resulted in a further decrease of cell viability associated with DZN exposure. In addition, the metabolite diazoxon was more toxic than DZN. Our results also revealed that THC alleviated DZN-induced cytotoxicity and reactive oxygen and nitrogen species (RONS) generation in HepG2 cells. In conclusion, our data provide novel insights into the involvement of biotransformation in the mechanisms of DZN-induced cytotoxicity and suggest that amelioration of RONS accumulation might be involved in the protective effect of THC on DZN-induced liver injury.