Monitoring gp43 antigenemia in Paracoccidioidomycosis patients during therapy

Paracoccidioidomycosis (PCM) is a systemic fungal disease that is particularly important among individuals living and working in rural areas of endemicity in Latin America. Detection of anti-Paracoccidioides brasiliensis antibodies is of limited value due to false-negative results. Detection of P. brasiliensis-gp43 circulating antigen is a practical approach for a specific diagnosis of the disease. In a previous study we described an inhibition enzyme-linked immunosorbent assay able to detect the 43-kDa P. brasiliensis antigen in sera of 100% of patients with the acute form of PCM and in 95.31 and 100% of patients with the chronic multifocal and unifocal forms of PCM. To investigate its potential application for the follow-up of PCM patients during treatment, antigen levels were monitored at regular intervals for up 8 to 12 months in serum samples from 23 patients. The results showed that treatment with itraconazole resulted in decreasing levels of circulating gp43 that were correlated with the reduction of anti-gp43 antibodies. It was also observed that by the end of 12 months of treatment gp43 levels were <5 microg/ml in all patients.     

Comparison of the cytotoxicity of two nitroheterocyclic drugs (NHCD) towards transformed and non-transformed cells.

The cytotoxicity of two nitroheterocyclic compounds (NHCD), Nitracrine, 1-nitro-9(3'3'-dimethylaminopropylamino) acridine (Polfa, Poland) and Quinifuryl, 2-(5'-nitro-2'-furanyl) ethenyl-4-[N-[4-(N,N-diethylamino)-1'-methylbutyl] carbamoyl] quinoline (Dr. N. M. Sukhova, Institute of Organic Synthesis, Riga, Latvian Republic), towards two lines of leukaemic cells and a line of non-transformed cells, was determined under normoxia conditions. Although both drugs showed significant cytotoxicity to all cell lines (LC(50) for 24h, < or = 2 microM) with that of Nitracrine exceeding Quinifuryl, their toxicity towards murine leukaemia P388 was substantially higher, compared to murine fibroblasts NIH3T3. In addition, the rate of cell death was also two- to three-fold higher in case of P388 cells versus NIH3T3. Interestingly, human erythroleukaemia K562 cells were shown to uptake the drugs 10 min after their addition to the tissue culture medium, while the LC(50) values were reached after a substantial delay of 3h. This delay might be due to the intracellular transformation of drugs required for cell killing.     

N-acetylcysteine protects against star fruit-induced acute kidney injury

Background: Star fruit (SF) is a popular fruit, commonly cultivated in many tropical countries, that contains large amount of oxalate. Acute oxalate nephropathy and direct renal tubular damage through release of free radicals are the main mechanisms involved in SF-induced acute kidney injury (AKI). The aim of this study was to evaluate the protective effect of N-acetylcysteine (NAC) on SF-induced nephrotoxicity due to its potent antioxidant effect.

Materials and methods: Male Wistar rats received SF juice (4?mL/100?g body weight) by gavage after a 12?h fasting and water deprivation. Fasting and water deprivation continued for 6?h thereafter to warrant juice absorption. Thereafter, animals were allocated to three experimental groups: SF (n?=?6): received tap water; SF?+?NAC (n?=?6): received NAC (4.8?g/L) in drinking water for 48?h after gavage; and Sham (n?=?6): no interventions. After 48?h, inulin clearance studies were performed to determine glomerular filtration rate. In a second series of experiment, rats were housed in metabolic cages for additional assessments.

Results: SF rats showed markedly reduced inulin clearance associated with hyperoxaluria, renal tubular damage, increased oxidative stress and inflammation. NAC treatment ameliorated all these alterations. Under polarized light microscopy, SF rats exhibited intense calcium oxalate birefringence crystals deposition, dilation of renal tubules and tubular epithelial degeneration, which were attenuate by NAC therapy.

Conclusions: Our data show that therapeutic NAC attenuates renal dysfunction in a model of acute oxalate nephropathy following SF ingestion by reducing oxidative stress, oxaluria, and inflammation. This might represent a novel indication of NAC for the treatment of SF-induced AKI.     

Expressed emotion and family burden in relatives of patients in first-episode psychosis

BACKGROUND

Evidence suggests that expressed emotion (EE) and family burden (FB) are phenomena that interact, but there is a lack of studies that analyze this association in patients in first-episode psychosis.

P450c17 deficiency in Brazilian patients: biochemical diagnosis through progesterone levels confirmed by CYP17 genotyping

P450c17 deficiency is an autosomal recessive disorder and a rare cause of congenital adrenal hyperplasia characterized by hypertension, hypokalemia, and impaired production of sex hormones. We performed a clinical, hormonal, and molecular study of 11 patients from 6 Brazilian families with the combined 17alpha-hydroxylase/17,20-lyase deficiency phenotype. All patients had elevated basal serum levels of progesterone (1.8-38 ng/ml; 0.57-12 pmol/liter) and suppressed plasma renin activity. CYP17 genotyping identified 5 missense mutations. The compound heterozygous mutation R362C/W406R was found in 1 family, whereas the homozygous mutations R96W, Y329D, and P428L were seen in the other 5 families. The R96W mutation has been described as the cause of p450c17 deficiency in Caucasian patients. The other mutations were not found in 50 normal subjects screened by allele-specific oligonucleotide hybridization (Y329D, R362C, and W406R) or digestion with HphI (P428L) and were recently found in other Brazilian patients. Therefore, we elucidated the genotype of 11 individuals with p450c17 deficiency and concluded that basal progesterone measurement is a useful marker of p450c17 deficiency and that its use should reduce the misdiagnosis of this deficiency in patients presenting with male pseudohermaphroditism, primary or secondary amenorrhea, and mineralocorticoid excess syndrome.     

Effects of 3D image-guided brachytherapy compared to 2D conventional brachytherapy on clinical outcomes in patients with cervical cancer: A systematic review and meta-analyses

PURPOSETo assess the effects of three-dimensional image-guided brachytherapy (3D BT) compared to bi-dimensional BT (2D BT) on clinical outcomes in patients with cervical cancer.METHODS AND MATERIALSWe searched PubMed/MEDLINE, EMBASE, Scopus, CENTRAL, Web of Science, and LILACS for studies assessing the effects of 3D BT versus 2D BT on clinical outcomes. Two reviewers independently screened retrieved citations, extracted data and assessed risk of bias from eligible studies. Hazard ratios (HR) were calculated from Kaplan-Meier curves considering the number of events, their timing and the followup of censored patients. We conducted meta-analyses of HR using the inverse-variance random-effects method. Risk Difference (RD) for toxicities were pooled using the Mantel–Haenszel random-effects method. We used the GRADE system to rate the certainty of evidence.RESULTSTwenty observational studies involving 4287 patients were included. The meta-analyses assessing the effect of 3D BT versus 2D BT on overall survival resulted in a HR of 0.78 (95%CI 0.62–0.98), HR of 0.75 (95%CI 0.62–0.90) for pelvic disease-free survival, HR of 0.93 (95%CI 0.81–1.06) for metastatic disease-free survival, and HR of 0.77 (95%CI 0.59–0.99) for local control. Grade 3–4 global and gastrointestinal toxicities were, respectively, 9% lower (95%CI 6% to 11%) and 5% lower (95%CI 2% to 8%) in patients receiving 3D BT versus 2D BT. Certainty of evidence was very low for all assessed outcomes.CONCLUSIONSOur study may suggest a benefit of 3D BT over conventional 2D BT on important clinical outcomes.     

Relationship between children physical activity,inflammatory mediators and lymphocyte activation: possible impact of social isolation (COVID-19)

Sport Sciences for Health - Lifestyle and body composition may be simultaneously responsible for immune response modulation. This study aimed to compare plasmatic adipokines concentration and...     

Root canal filling quality of mandibular molars with EndoSequence BC and AH Plus sealers: A micro‐CT study

The aim of this study was to compare, by micro‐computed tomography (micro‐CT) analysis, the obturation quality of two filling methods: the single‐cone technique with the bioceramic EndoSequence BC sealer and the continuous wave technique with the resin‐based AH Plus sealer. Twenty mandibular molars were divided into two groups (n = 10) according to the sealer used. Only the mesial roots, which are known to have mostly two canals, were used. The specimens were scanned before and after instrumentation and after obturation. Root canal volume after instrumentation and filling volume were calculated to obtain the percentage volumes of filling, voids and gaps. All specimens presented final volumes that were smaller than the initial volumes (P < 0.05). There was no significant difference between groups for filling volume, voids and gaps (P > 0.05). Using two filling methods, EndoSequence BC and AH Plus promoted a similar root filling quality in mesial roots of mandibular molars. Neither sealer was able to fill the root canal system completely.