Antifungal agents incorporated in denture base materials: a scoping review of the current evidence and technology prospecting.

BACKGROUND: The aim of this study was to summarize existing data and perform technological prospecting on the effect of incorporating antifungal agents into denture base materials in inhibiting Candida spp., as well as to explore the antimicrobial properties of these materials. METHODS: A comprehensive electronic search was carried out in six major bibliographic databases (PubMed, Scopus, Embase, Cochrane Library, Web of Science and Lilacs) until February 2024. In addition, international patent databases were also examined. The search process, study and patent selection, data extraction and risk of bias assessment were carried out independently by researchers. The collected data underwent qualitative analysis. RESULTS: A total of 10 718 articles were identified in the searched databases, of which 40 documents were included for qualitative data analysis (articles: 31; patents: 9). The majority of the studies focused on investigating tissue conditioners (n = 14) and acrylic resins (n = 14). The primary antifungal agents studied were nystatin (n = 15) and fluconazole (n = 13). The most commonly utilized microbiological evaluation methodology was the agar diffusion test (n = 16), followed by the microdilution (n = 7) and biofilm formation assays (n = 7). All of the studies investigated the inhibitory effect of these materials against Candida species. CONCLUSION: The incorporation of antifungal agents into denture base materials has been extensively studied and has shown a significant inhibitory response against Candida spp. across various methodological assays.

Influence of Frailty Status on Pain, Disability, and Quality of Life in Older Adults with Acute Low Back Pain: Results from the Back Complaints in the Elders (BACE-Brazil) Study.

A cross-sectional analysis was conducted using data from a prospective cohort study to investigate whether frailty is associated with pain intensity, disability caused by low back pain (LBP), and quality of life in an older population with acute non-specific LBP. Six hundred and two individuals with a mean age of 67.6 (standard deviation [SD] 7.0) years were included in the analysis. In relation to frailty status, 21.3 per cent of the sample were classified as robust, 59.2 per cent were classified as pre-frail, and 19.5 per cent were classified as frail. In the unadjusted analysis, pre-frail and frail groups showed significantly higher pain and disability scores than the robust group. Moreover, the same two groups exhibited lower scores in both physical and mental domains of quality of life than the robust group. After adjusting for socio-demographic and clinical variables, disability scores and the physical component of quality of life were significantly associated with frailty. In older adults with acute LBP, frailty is associated with more disability and worse scores in the physical component of quality of life.

Synthesis of benzoylthiourea derivatives and analysis of their antibacterial performance against planktonic Staphylococcus aureus and its biofilms.

Following the appearance of several antimicrobial agents to control the spread of infections, two major challenges have emerged: (i) the occurrence and blowout of multiresistant bacteria and the increase of chronic diseases and (ii) difficult-to-eradicate infections. In this study, we tested five benzoylthiourea derivatives for their ability to inhibit and stop bacterial growth and evaluated the possible influence of 1,2,4-triazolyl-benzoylthiourea derivative 4 on the formation and eradication of Staphylococcus aureus biofilms. Benzoylthiourea derivatives 4, 6, 10, 11 and 13 were obtained in one or two steps with low cost and subjected to tests to identify their minimum inhibitory concentration (MIC) and minimum bactericidal concentration. In vitro tests were also performed to assess their effects on biofilm formation and in preformed biofilms and scanning electron microscopy was used to visualize the effects on biofilm formation. The 1,2,4-triazolyl-benzoylthiourea derivative 4 showed bacteriostatic activity against the S. aureus HU25 clinical strain with an MIC of 16 µg ml-1 , which is below the toxic concentration (at 2500 µg ml-1 , 62·25% of the cells remained viable). Compound 4 also effectively prevented biofilm formation at the three subinhibitory concentrations tested (1/2 MIC, 1/4 MIC and 1/8 MIC) as confirmed by scanning electron microscopy. For breakdown of formed biofilms, the main influence was at a subinhibitory concentration (1/2 MIC). These findings make compound 4 a strong candidate for studies on the development of new antimicrobial and antibiofilm agents.

Common germline haplotypes and genotypes identified in BRCA2 exon 11 of dogs with mammary tumours and histopathological analyses.

The canine BRCA2 is a tumor supressor gene which encodes the BRCA2 protein, involved in DNA repair through interaction with the RAD51 recombinase. This process is mediated by eigth BRC repeats that are encoded by BRCA2 exon 11. Two variants corresponding to human mutations in human BRC3 repeat have been reported in canine BRC3 repeat. In addition, other variants have also been described in canine BRCA2 exon 11. Considering the importance of polymorphisms in human BRCA2 to breast cancer development, this study aimed to investigate the frequency of variants in BRCA2 exon 11 in 48 blood and tissue DNA samples from bitches with canine mammary tumors (CMT), as well as, to analyze tumor stage and histopathological features. Seven Single Nucleotide Polymorphisms (SNPs) were identified, three of which were evaluated as possibily or probably deleterious variant. Interestingly, almost all the 22 mammary tumors (except one) which presented a clinical staging equal to or greater than III carried at least one mutant allele of these three variants. Besides that, no statistically significant correlation was observed between any of the reported SNPs in heterozygosis or homozygosis and either dogs data (such as breed, age or disease stage) or mammary tumors histopathological characteristics. A total of 97.9% of bitches had one to three polymorphisms of the seven identified in this study, which suggests a possibly correlation between the canine BRCA2 exon 11 polymorphisms and mammary carcinogenesis.

Avaliação morfofuncional do enxerto de túnica albugínea suína na cistoplastia em ratos / Morpho-fuctional evaluation of porcine tunica albuginea as a graft for cystoplasty in rats

O objetivo deste trabalho é avaliar o uso da túnica albugínea suína na cistoplastia em ratos, avaliando funcionalidade, capacidade de reparação do órgão e possibilidades de complicações. Foram selecionados 30 ratos Wistar, machos, de seis meses de idade, divididos em: um grupo teste (TA), em que os animais receberam o enxerto de túnica albugínea suína após a cistectomia parcial e um grupo controle (C), em que os animais sofreram somente a cistectomia parcial. Os animais pertencentes a ambos os grupos foram divididos igualmente em subgrupos de cinco animais cada, que sofreram eutanásia em sete, 28 e 42 dias de pós-operatório. Foi realizada uma análise macroscópica e, posteriormente, uma análise histopatológica da região da ferida cirúrgica. Aos sete e 28 dias, os animais pertencentes ao grupo C e ao grupo TA apresentaram urotelização, regeneração da lâmina própria e da musculatura, porém o grupo TA apresentou menores sinais inflamatórios e maior organização tecidual, principalmente com relação à formação das fibras musculares. Aos 42 dias de pós-operatório, ambos os grupos já apresentavam características histológicas normais. Concluiu-se que o enxerto de túnica albugínea suína obteve sucesso na regeneração da bexiga de ratos, mantendo a funcionalidade do órgão, sem rejeição, e favorecendo a migração celular.(AU)

The aim of this study is to evaluate porcine tunica albuginea as a graft for cystoplasty in rats, regarding bladder function, capacity and possible complications. 30 male Wistar rats with six monthes of age have been selected and separated into two different groups: A test group (TA) in which the animals received a tunica albuginea graft after partial cystectomy and a control group (C) in which partial cystectomy was performed, followed by bladder suture. In each group the animals were euthanized at seven, 28 and 42 days after surgery. Macroscopic and Histological analysis have been performed. At seven and 28 days after surgery the samples from both groups had urothelial lining upon a lamina propria and smooth muscle fibers in regeneration process. However, the TA group showed less inflammatory signs and more organized structure, mainly regarding the smooth muscle formation. At 42 days after surgery all groups showed a bladder wall structure qualitatively identical to the normal tissue. We could conclude that tunica albuginea graft is able to maintain bladder function and support cellular migration without any kind of rejection.(AU)

Avaliação morfofuncional do enxerto de túnica albugínea suína na cistoplastia em ratos / Morpho-fuctional evaluation of porcine tunica albuginea as a graft for cystoplasty in rats

O objetivo deste trabalho é avaliar o uso da túnica albugínea suína na cistoplastia em ratos, avaliando funcionalidade, capacidade de reparação do órgão e possibilidades de complicações. Foram selecionados 30 ratos Wistar, machos, de seis meses de idade, divididos em: um grupo teste (TA), em que os animais receberam o enxerto de túnica albugínea suína após a cistectomia parcial e um grupo controle (C), em que os animais sofreram somente a cistectomia parcial. Os animais pertencentes a ambos os grupos foram divididos igualmente em subgrupos de cinco animais cada, que sofreram eutanásia em sete, 28 e 42 dias de pós-operatório. Foi realizada uma análise macroscópica e, posteriormente, uma análise histopatológica da região da ferida cirúrgica. Aos sete e 28 dias, os animais pertencentes ao grupo C e ao grupo TA apresentaram urotelização, regeneração da lâmina própria e da musculatura, porém o grupo TA apresentou menores sinais inflamatórios e maior organização tecidual, principalmente com relação à formação das fibras musculares. Aos 42 dias de pós-operatório, ambos os grupos já apresentavam características histológicas normais. Concluiu-se que o enxerto de túnica albugínea suína obteve sucesso na regeneração da bexiga de ratos, mantendo a funcionalidade do órgão, sem rejeição, e favorecendo a migração celular.(AU)

The aim of this study is to evaluate porcine tunica albuginea as a graft for cystoplasty in rats, regarding bladder function, capacity and possible complications. 30 male Wistar rats with six monthes of age have been selected and separated into two different groups: A test group (TA) in which the animals received a tunica albuginea graft after partial cystectomy and a control group (C) in which partial cystectomy was performed, followed by bladder suture. In each group the animals were euthanized at seven, 28 and 42 days after surgery. Macroscopic and Histological analysis have been performed. At seven and 28 days after surgery the samples from both groups had urothelial lining upon a lamina propria and smooth muscle fibers in regeneration process. However, the TA group showed less inflammatory signs and more organized structure, mainly regarding the smooth muscle formation. At 42 days after surgery all groups showed a bladder wall structure qualitatively identical to the normal tissue. We could conclude that tunica albuginea graft is able to maintain bladder function and support cellular migration without any kind of rejection.(AU)

Outbreaks of colistin-resistant and colistin-susceptible KPC-producing Klebsiella pneumoniae in a Brazilian intensive care unit.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE), especially those that produce Klebsiella pneumoniae carbapenemase (KPC) and are associated with colistin resistance, pose a severe health threat due to the limited treatment options. AIM: To describe two outbreaks of KPC-producing K. pneumoniae in an adult intensive care unit (AICU) in Brazil. In May 2015, 14 patients had colistin-susceptible KPC-producing strains (ColS-KPC), and in July 2015, nine patients had colistin-resistant KPC-producing strains (ColR-KPC). METHODS: Between September 2014 and August 2015, we performed surveillance at a university hospital and all CRE were tested for blaKPC genes. Clonality was investigated by pulsed-field gel electrophoresis. Resistance to colistin was confirmed by broth microdilution method. Consumption of carbapenems and colistin was expressed as defined daily doses. FINDINGS: In all, 111 patients with CRE were identified during the surveillance period; K. pneumoniae was the major isolate (77.13%). The two outbreaks were identified when infection rates (KPC per 1000 patient-days) exceeded the background level. Rates of carbapenem and colistin consumption were high. Control measures (bedside alcohol gel, contact precautions, regular rectal swabs) did not curtail the outbreaks. Mortality rates were 42.9% and 44.4% for ColS-KPC- and ColR-KPC-infected patients, respectively. After the death of four infected patients with ColR-KPC, the unit was closed to new admissions. CONCLUSION: Our experience demonstrates the serious risks presented by KPC, and especially ColR-KPC, in Brazilian AICUs. Selective pressure from excessive antibiotic use and transmission on healthcare workers' hands were likely the major factors in transmission.

Patients' perceived level of social isolation affects the prognosis of low back pain.

BACKGROUND: Perceived social isolation is prevalent among patients with low back pain (LBP) and could be a potential prognostic factor for clinical outcomes following an episode of LBP. METHODS: A secondary analysis of an original prospective cohort study, which investigated the validity of the Danish version of the STarT Back Screening Tool (STarT), investigated whether social isolation predicts the clinical outcomes of disability, anxiety, depression and pain catastrophizing in people with LBP. Patients with LBP of any duration (N = 204) from Middelfart, Denmark, were included. Social isolation was measured at baseline using the friendship scale (score ranges from 0 to 24, with lower values meaning higher perceived social isolation), and outcomes were measured at baseline and at 6-month follow-up. Regression models investigated whether social isolation at baseline predicted the outcomes at 6-month follow-up. RESULTS: Some level of social isolation was reported by 39.2% of the participants (n = 80) with 5.9% (n = 12) being very socially isolated. One-point difference on social isolation predicted one point on a 100-point disability scale (adjusted unstandardized coefficient: -0.91; 95% confidence interval (CI): -1.56 to -0.26). Social isolation predicted anxiety; however, a change of one point on the social isolation scale represents a difference of only 0.08 points on a 22-point scale in anxiety (95% CI: 0.01-0.15) and is unlikely to denote clinical importance. Social isolation did not predict pain catastrophizing or depression. CONCLUSIONS: Patients' perceived social isolation predicts disability related to LBP. Further understanding of the role of social isolation in LBP is warranted.

Heritability and lifestyle factors in chronic low back pain: results of the Australian twin low back pain study (The AUTBACK study).

BACKGROUND: Heritability and population-specific lifestyle factors are considered to significantly contribute to chronic low back pain (LBP), but traditional population studies fail to (1) adjust for genetics; and (2) use standard and validated definitions for LBP and for lifestyle factors. METHODS: Using a classical and a co-twin control study design and validated definitions for chronic LBP and lifestyle variables, we explored the relative contribution of genetics and environment on the prevalence of chronic LBP in a sample of adult Australian twins. RESULTS: Data from 105 twin pairs showed that the prevalence of chronic LBP is significantly determined by genetic factors (heritability = 32%). Additionally, monozygotic twins were five times more likely to have chronic LBP than dizygotic twins when one of the siblings of the pair was affected. In a case-control analysis (n = 38 twin pairs), an exploratory analysis showed higher prevalence of chronic LBP associated with light walking exercises and vigorous gardening or heavy work around the house. Daily time spent in sitting was also positively associated with chronic LBP, but not moderate physical activities such as jogging, cycling and gentle swimming. In the final multivariate model, only time spent in vigorous gardening or heavy work around the house remained associated with chronic LBP (odds ratio 6.5; 95% confidence interval 1.47-28.8). CONCLUSIONS: The type, frequency and duration of physical activity may be important to understand risk factors for chronic LBP. The causation path between chronic LBP and people's engagement in activities involving frequent bending and twisting such as gardening and housework should be further investigated.

Self-reported moderate-to-vigorous leisure time physical activity predicts less pain and disability over 12 months in chronic and persistent low back pain.

BACKGROUND: Physical deconditioning in combination with societal and emotional factors has been hypothesized to compromise complete recovery from low back pain (LBP). However, there is a lack of longitudinal studies designed to specifically investigate physical activity as an independent prognostic factor. We conducted a prognostic study to investigate whether levels of leisure time physical activity are independently associated with clinical outcomes in people seeking care for chronic and persistent LBP. METHODS: A total of 815 consecutive patients presenting with LBP to an outpatient spine centre in secondary care were recruited. Separate multivariate linear regression analyses were performed to investigate whether levels of leisure time physical activity (i.e., sedentary, light and moderate-to-vigorous leisure time physical activity levels) predict pain and disability at 12-month follow-up, after adjusting for age, pain, episode duration, disability, neurological symptoms, depression and fear of movement. RESULTS: Final models showed evidence of an association between baseline physical activity and 12-month outcomes (p < 0.001). In both models, the moderate-to-vigorous physical activity group reported less pain and disability compared with the sedentary group. CONCLUSIONS: Our findings suggest that physical activity levels may have a role in the prognosis of LBP. Specific domains of physical activity warrant further investigation to better understand this association.

Sex differences in insulin resistance in GABAB1 knockout mice.

AIMS: We have previously demonstrated that the absence of functional GABA B receptors (GABABRs) disturbs glucose homeostasis in GABAB1KO mice. The aim of this work was to extend our studies of these alterations in GABAB1KO mice and investigate the sexual differences therein. MAIN METHODS: Male and female, GABAB1KO and WT mice were used. Glucose and insulin tolerance tests (GTT and ITT), and insulin and glucagon secretion tests (IST and GST) were performed. Blood glucose, serum insulin and hyperglycemic hormones were determined, and HOMA-IR calculated. Skeletal muscle insulin receptor ß subunit (IRß), insulin receptor substrates 1/2 (IRS1, IRS2) and hexokinase-II levels were determined by Western blot. Skeletal muscle insulin sensitivity was assessed by in vivo insulin-induced Akt phosphorylation (Western blot). Food intake and hypothalamic NPY mRNA expression (by qPCR) were also evaluated. KEY FINDINGS: Fasted insulin and HOMA-IR were augmented in GABAB1KO males, with no alterations in females. Areas under the curve (AUC) for GTT and ITT were increased in GABAB1KO mice of both genders, indicating compromised insulin sensitivity. No genotype differences were observed in IST, GST or in IRß, IRS1, IRS2 and hexokinase-II expression. Akt activation was severely impaired in GABAB1KO males while no alterations were observed in females. GABAB1KO mice showed increased food intake and NPY expression. SIGNIFICANCE: Glucose metabolism and energy balance disruptions were more pronounced in GABAB1KO males, which develop peripheral insulin resistance probably due to augmented insulin secretion. Metabolic alterations in females were milder and possibly due to previously described reproductive disorders, such as persistent estrus.

A rational approach to the regioselective deacetylation of 2',3',5'-tri-O-acetyluridine by Novozym 435 catalysed alcoholysis.

To give a rational explanation for the behaviour of 2',3',5'-tri-O-acetyluridine (TAU) catalysed alcoholysis using Novozym 435, the commercial biocatalyst with immobilized Candida antarctica lipase B (CALB), a set of experiments analyzing the role of the alcohol/substrate (A/S) molar ratio, alcohol/biocatalyst (A/B) and substrate/biocatalyst (S/B) mass ratios were carried out. At a A/S=120 and a S/B=6.16, 2',3'-di-O-acetyluridine (DAU) was obtained in 92% at 22h. The observed trend towards the exclusive formation of DAU at very high alcohol amounts can be explained on the basis of the change of substrate orientation from normal to inverse. The simple molecular modelling analysis supports that key O/H atoms from TAU and the resulting intermediates display the adequate distances to generate productive binding only when the inverse coordination of TAU is present through the 5'-moiety of TAU, at high ethanol concentrations. At these conditions a possible allosteric-like effect of ethanol, combined with water in an H-network in the catalytic triad and in its neighbourhood, could explain the high selectivity towards the production of DAU at selected conditions.

Seasonal characterization of antioxidant responses in plants of Ipomoea nil cv. Scarlet O'Hara.

Reactive oxygen species can be produced in leaf cells during normal aerobic metabolism or in a variety of exogenous factors, which may cause oxidative damage to plants, unless they have an efficient antioxidant defense system, consisting of enzymatic and non-enzymatic substances. This work raised the hypothesis that plants of Ipomoea nil cv. Scarlet O'Hara, a native species and ornamental vine of the tropics, might tolerate oxidative stress factors imposed by natural fluctuations in weather conditions through changes in the antioxidant profile.The objective of this study was to determine the variations in three leaf antioxidants in plants growing inside a greenhouse without air pollutants and exposed to varying meteorological conditions throughout the four seasons of the year and to observe if such variations are related to the oscillations in meteorological factors. Four experimental campaigns were carried out, one in each season of 2006. Each campaign lasted 28 days and started with 45 plants. Ascorbic acid (AA) concentrations and superoxide dismutase (SOD) and peroxidase (POD) activities were determined in leaves of five plants in nine sampling days of each campaign. The antioxidant responses oscillated throughout the year. The highest values were found during the spring. This seasonal antioxidant profile was associated to variations in temperature, relative humidity and global radiation. Plants of this cultivar may then tolerate oxidative stress naturally imposed by meteorological conditions.

Synthesis and antimycobacterial evaluation of N'-(E)-heteroaromaticpyrazine-2-carbohydrazide derivatives.

A series of nine N'-(E)-heteroaromatic-pyrazine-2-carbohydrazide derivatives (5a-f and 6a-c) have been synthesized and evaluated against M. tuberculosis ATCC 27294 using the micro plate Alamar Blue assay (MABA), being the activities expressed as the minimum inhibitory concentration (MIC) in µg/ml. Compounds 5a and 5f exhibited potent activities (3.12 and 50µg/mL, respectively) when compared to the first line drug pyrazinamide (MIC>100 µg/mL). Afterwards, these compounds were evaluated for their cell viabilities in non-infected and infected macrophages with Mycobaterium bovis Bacillus Calmette-Guerin (BCG) and 5f was not cytotoxic to host cells in the effective concentration to inhibit the growth of M. tuberculosis.

The Brazilian database on pregnancy in multiple sclerosis.

OBJECTIVES: To report the results from the Brazilian database on multiple sclerosis (MS) and pregnancy. METHODS: Retrospective data from MS patients who became pregnant at any time of their disease were sent to a Brazilian database, using a specific file for this purpose. RESULTS: Data on 128 women (142 pregnancies) from 30 neurologists working in 21 cities in Brazil were collected. Patients' average age at pregnancy was 29.8 years (range 16-42). EDSS at start of pregnancy was 1.5±1.4; and the relapse rate in the year preceding pregnancy was 1.2±1.5. Exposure to medication at any time during pregnancy was high (69.7%): 48.6% to interferon beta; 14.1% to glatiramer acetate; and 7% to other immunomodulatory and immunosuppressive drugs. There was a significant decrease in relapse rate during pregnancy. The prevalence of complications was relatively low, with 4.9% of obstetric and 1.4% neonatal unfavorable outcomes. CONCLUSIONS: Our patients had low degrees of disability, short histories of disease, high drug exposure, and relatively high relapse rate in the year previous to pregnancy. Obstetric and neonatal outcomes were successful in over 90% of our patients.

Oclusão parcial externa reversível do prepúcio no preparo de rufiões bovinos / Oclusión parcial externa reversible del prpucio en el preparo de rufianes bovinos / Partial extraneous occlusive reversible of the prepuce in preparation of teaser bull

No presente estudo foram utilizados dez bovinos mestiços, com idade variando de dois a quatro anos, com a finalidade de demonstrar uma nova técnica no preparo de rufião, em que a principal característica é a sua reversibilidade, além de ser de simples execução e economicamente viável. A técnica resume-se na colocação de uma abraçadeira plástica ao redor do prepúcio do animal impedindo a exposição do pênis. O material necessário é mínimo, constando de trocáter, gabarito e abraçadeira plástica. Após o procedimento os animais se encontravam aptos para identificação de vacas em estro, o que pode ser comprovado durante todo o período de observação. Ao final dos três meses, a abraçadeira plástica foi removida e os animais demonstraram interesse pelas fêmeas e expuseram o pênis normalmente. A técnica é eficiente, reversível e não compromete a libido, a fisiologia e o bem estar dos animais.(AU)

Ten cattle cross-breed between two and four years old have been used to assay a new technique in preparation of teaser bull with the principal characteristic is the sweats reversibility in addition to be of simple execution and economically viable. The technique if summarizes on placement from a clamp plastic about of the prepuce of the animal withheld the exposition of the penis. The material necessary is minimum, constant of trocater, pattern and clamp plastic. Right after the procedure the animals used to be apt the identify females in heat the one to may be aver all day period of observation. The end of the three months, the clamp plastic was removed and the animals demonstrated interest by females and capacity of exposition the penis. We concluded what the technique is all-around, reversible and no engages the libido, physiology and principally the animals welfare.(AU)

En este estudio se utilizó diez bovinos mestizos, con edad variando de dos a cuatro años, con la finalidad de demostrar una nueva técnica en el preparo de rufián, en que la principal característica es su reversibilidad, además de ser de simple ejecución y económicamente viable. La técnica se resume en la colocación de una abrazadera plástica alrededor del prepucio del animal impidiendo la exposición del pene. El material necesario es mínimo, constando de trocáter, plantilla y abrazadera plástica. Después del procedimiento los animales se encontraban aptos para identificación de vacas en celo, lo que puede ser comprobado durante todo el periodo de observación. Al fin de tres meses, la abrazadera plástica fue removida y los animales demostraron interés por las hembras y expusieron el pene normalmente. La técnica es eficiente, reversible y no compromete la libido, la fisiología y el bienestar de los animales.(AU)

Simultaneous determination of sulfamethoxazole and trimethoprim in biological fluids for high-throughput analysis: comparison of HPLC with ultraviolet and tandem mass spectrometric detection.

The comparison of two methods based on online solid phase extraction-liquid chromatography with UV (SPE-LC-UV) or mass spectrometry detection (SPE-LC-MS/MS) for the simultaneous quantification of sulfamethoxazole (SMZ) and trimethoprim (TMP) is presented. The methods were validated and proved to be accurate. The analysis of standard samples for SMZ at concentrations of 0.5, 1.5, 25 and 50microg/mL demonstrated a relative standard deviation of less than 6% for both methods (n=18), while TMP samples at concentrations of 0.05, 0.15, 1.5 and 5.0microg/mL were analyzed with R.S.D. of less than 4% (n=18). The method with mass spectrometric detection was approximately six times more sensitive than the method with ultraviolet detection. The total run time for the SPE-LC-MS/MS was 2.5min per sample as opposed to 18.0min for the SPE-LC-UV method. The method with MS detection in comparison with UV detection proved to be more rugged and was successfully applied to pharmacokinetics studies.

Computational study of the structure and behavior of aqueous mixed system sodium unsaturated carboxylate-dodecyltrimethylammonium bromide.

The mixed surfactant system sodium 10-undecenoate (SUD)-dodecyltrimethylammonium bromide (DTAB) was studied by computational simulation to determine the composition and structure of the mixed microstructures. Results were contrasted with experimental data obtained from literature and our own laboratory. The modelization predicts spherical or cylindrical micelles with a preferential composition of SUD-DTAB of about 1:2, while the system predicts a lamellar structure with a proportion of 1:1 when SUD is replaced by the saturated soap sodium undecanoate. The model also predicts the deep inclusion of bromide ions in the micelle Stern layer. All predictions were in agreement with previous experimental results.

The role of purinergic P2X7 receptors in the inflammation and fibrosis of unilateral ureteral obstruction in mice.

Receptors of the P2X7 type have been demonstrated in granulocytes, monocytes/macrophages, B and T lymphocytes, and have been involved in several cellular mechanisms including those related to inflammation and immunological response. This study attempted to investigate the role of these receptors on the inflammatory and fibrogenic response in the kidneys of unilateral ureteral obstruction (UUO), by using P2X7 knockout mice (-/-). C57Bl6 mice were submitted to left UUO and killed after 7 and 14 days. Histopathology using hematoxylin-eosin, periodic-acid Schiff and Sirius-red staining, immunohistochemistry for macrophages, myofibroblasts, transforming growth factor-beta (TGF-beta)1 and P2X7, and immunofluorescence for apoptotic cells (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling) were performed. Protocols were as follows: (1) control; (2) sham; (3) control P2X7 (-/-); (4) sham P2X7 (-/-); (5) UUO wild type (WT); (6) UUO P2X7 (-/-). Myofibroblasts and Sirius-red staining were significantly lower in UUO P2X7 (-/-) mice at days 7 and 14, compared to UUO WT. Kidneys from UUO P2X7 (-/-) mice showed reduced number of inflammatory cells at day 14 but not at day 7, compared to UUO WT. TGF-beta1 was less in UUO P2X7 (-/-) mice at days 7 and 14 when compared to UUO WT. Macrophage infiltration and tubular apoptosis were lower in UUO P2X7 (-/-) at day 14 but not at day 7, compared to UUO WT. P2X7 was expressed only in tubular epithelial cells at day 7 of UUO WT mice. These findings constitute the first evidence that P2X7 receptors are implicated in macrophage infiltration, collagen deposition and apoptosis in response to ureteral obstruction in mice.