Current treatments for female primary stress urinary incontinence.

Stress urinary incontinence (SUI) affects millions of women worldwide. Pelvic floor muscle training is the first-line treatment for SUI, and if this fails, midurethral sling surgery has become the gold-standard treatment. More recently, complications from midurethral mesh slings, particularly chronic pain and dyspareunia, have become a major concern. Although traditional SUI treatments, such as colposuspension and fascia slings, are used, the future of SUI treatment likely will rely on less invasive alternatives. Modern bulking agents could have the potential to become a first-line treatment for SUI, but further long-term studies are needed. Patients should be involved in decision-making prior to any surgery to ensure that they are aware of the risks and also any reasonable treatment alternatives. Furthermore, the effectiveness of a procedure should be balanced with its invasiveness and possible risks to provide women individually with the best possible treatment option.

Ecotoxicity evaluation of a WWTP effluent treated by solar photo-Fenton at neutral pH in a raceway pond reactor.

Some pollutants can be resistant to wastewater treatment, hence becoming a risk to aquatic and terrestrial biota even at the very low concentrations (ng L-1-µg L-1) they are commonly found at. Tertiary treatments are used for micropollutant removal but little is known about the ecotoxicity of the treated effluent. In this study, a municipal secondary effluent was treated by a solar photo-Fenton reactor at initial neutral pH in a raceway pond reactor, and ecotoxicity was evaluated before and after micropollutant removal. Thirty-nine micropollutants were identified in the secondary effluent, mainly pharmaceuticals, with a total concentration of ≈80 µg L-1. After treatment, 99 % microcontaminant degradation was reached. As for ecotoxicity reduction, the assayed organisms showed the following sensitivity levels: Tetrahymena thermophila > Daphnia magna > Lactuca sativa > Spirodela polyrhiza ≈ Vibrio fischeri. The initial effluent showed an inhibitory effect of 40 % for T. thermophila and 20 % for D. magna. After 20 min of photo-Fenton treatment, no toxic effect was observed for T. thermophila and toxicity dropped to 5 % for D. magna. Graphical abstract Ecotoxicity removal by solar photo-Fenton at neutral pH. ᅟ.

Studies Introducing Costimulation Blockade for Vascularized Composite Allografts in Nonhuman Primates.

Vascularized composite allografts (VCAs) are technically feasible. Similar to other organ transplants, VCAs are hampered by the toxicity and incomplete efficacy associated with conventional immunosuppression. Complications attributable to calcineurin inhibitors remain prevalent in the clinical cases reported to date, and these loom particularly large given the nonlifesaving nature of VCAs. Additionally, acute rejection remains almost ubiquitous, albeit controllable with current agents. Costimulation blockade offers the potential to provide prophylaxis from rejection without the adverse consequences of calcineurin-based regimens. In this study, we used a nonhuman-primate model of VCA in conjunction with immunosuppressive regimens containing combinations of B7-specific costimulation blockade with and without adhesion blockade with LFA3-Ig to determine what adjunctive role these agents could play in VCA transplantation when combined with more conventional agents. Compared to tacrolimus, the addition of belatacept improved rejection free allograft survival. The combination with LFA3-Ig reduced CD2(hi) memory T cells, however did not provide additional protection against allograft rejection and hindered protective immunity. Histology paralleled clinical histopathology and Banff grading. These data provide the basis for the study of costimulation blockade in VCA in a relevant preclinical model.

Antiviral activity-guided fractionation from Araucaria angustifolia leaves extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Araucaria angustifolia (Bert.) O. Kuntze (Araucariaceae) is a Brazilian medicinal plant traditionally used for the treatment of various illnesses including dried skin, wounds, shingles, and sexually transmitted diseases. AIM OF THE STUDY: The rationale of the study was to provide evidence of its antiherpes activity in order to confirm its popular use that could be related to herpes disease. MATERIALS AND METHODS: The crude hydroethanolic extract (HE) obtained from Araucaria angustifolia leaves was submitted to a sequential liquid-liquid extraction with solvents of increased polarity. The HE and fractions obtained were evaluated for cytotoxicity and antiherpes activity (Herpes Simplex Virus type 1) by MTT assay. The most active fractions were selected to perform an in vitro antiviral activity-guided chromatographic fractionation. RESULTS: The ethyl acetate (EA) and n-butanol (NB) fractions have shown the best results for antiherpetic activity and their further fractionation yielded 22 subfractions. From these subfractions, 14 were active, and the most potent antiherpetic activity was obtained for NB1-4 subfraction with selectivity index (SI) of 57.51. Chemical analysis of NB1-4 subfractions revealed the presence of proanthocyanidins and the known biflavonoids (bilobetin, II-7-O-methyl-robustaflavone and cupressuflavone). The same biflavonoids have been detected in EA subfractions. CONCLUSION: The present study has shown that the hydroethanolic extract from Araucaria angustifolia leaves as well as many different fractions and subfractions exhibited antiherpes activity, supporting the use of this plant species in folk medicine.

Comprehensive two-dimensional gas chromatography for fingerprint pattern recognition in olive oils produced by two different techniques in Portuguese olive varieties Galega Vulgar, Cobrançosa e Carrasquenha.

For olive oil production a metal hammer-decanter olive processing line was compared to a traditional metal hammer-press line, a discontinuous method which, if properly used, yields high-quality virgin olive oils. Galega, Carrasquenha and Cobrançosa olives (traditional Portuguese varieties) were studied. The analysis of the aroma compounds was performed after headspace-solid phase micro extraction. The analytical results obtained after comprehensive gas chromatography in tandem with time of flight mass spectrometry (GCxGC/ToFMS) for these three different olive oil varieties, from a single year harvest and processed with two different extraction technologies, were compared using statistical image treatment, by means of ImageJ software, for fingerprint recognitions and compared with principal component analysis when the area data of each chromatographic spot of the contour plots were considered. The differences used to classify the olive oils studied under different groups after principal component analysis were observed independently of the treatment used (peak areas or the sum of the pixels counts). When the individual peak areas were considered, more then 75.7% of the total variance is explained by the first two principal components while in the case where the data were subjected to image treatment 84.0% of the total variance is explained by the first two principal components. In both cases the first and second principal components present eigenvalues higher then 1.0. Fingerprint image monitoring of the aroma compounds of the olive oil allowed a rapid differentiation of the three varieties studied as well as the extraction methods used. The volatile compounds responsible for their characterization were tentatively identified in a bi-dimensional polar/non-polar column set in the GCxGC/Tof-MS apparatus. This methodology allowed the reduction of the number of compounds needed for matrices characterization, preserving the efficiency of the discrimination, when compared with the traditional methods where the identification of all peaks is needed.

Impact of malolactic fermentation on low molecular weight phenolic compounds.

A reversed phase liquid chromatography-DAD method is proposed for analysis of major non-flavonoid phenolic compounds in wines. The method employed a mixture of acetic acid, water and methanol as eluents and was used to evaluate the impact of malolactic fermentation in low molecular phenolic compounds. The wines analyzed underwent different treatments, like the addition of a pectolytic enzyme or lysozyme, and the way malolactic fermentation was carried out-spontaneously or with the inoculation of two different commercial lactic bacteria. The main result observed was the disappearance of hydroxycinnamoyltartaric acids and the increase of resultant free forms, regardless the way malolactic fermentation was carried out.

Different multidimensional chromatographic approaches applied to the study of wine malolactic fermentation.

Different multidimensional chromatographic techniques were used to study wine aroma pattern changes during malolactic fermentation (MLF). Ethyl lactate enantiomeric ratios were determined using on-line multidimensional gas chromatography. The values found agree with a spontaneous MLF. Off-line multidimensional HPLC/GC was used to deconvolute and enrich the sample and ease enantioselective chromatography. Chiral compound enantiomeric ratio changes during MLF were monitored. Evaluation of enantiomeric ratio changes during MLF has never been studied. (R,R), (S,S) and meso-butane-2,3-diol and pentane-2,4-diol (reported in wines for the first time) were submitted to untrained sensory panel tests. All stereoisomers revealed different sensory notes; pentane-2,4-diol showed an aromatic impact.

In vitro metabolism of pregnenolone to 7alpha-hydroxypregnenolone by rainbow trout embryos.

Tissues taken from rainbow trout embryos at several developmental stages, were incubated in the presence of radioactively-labelled pregnenolone in order to determine the capability of salmonid embryos to metabolize steroids, such as pregnenolone, that are incorporated into the oocyte during gonadal growth and maturation. High performance liquid chromatography was used to separate the steroid products, and gas chromatography-mass spectrometry was applied for the chemical identification of the product. 7alpha-Hydroxypregnenolone, previously known to be produced only by ovarian tissues, was found to be the sole metabolite of pregnenolone metabolism by rainbow trout embryos. Sulfate and glucuronide conjugated forms of 7alpha-hydroxypregnenolone were also produced. We hypothesize that this metabolite provides a pathway for excretion of pregnenolone, enabling the embryo to maintain its own steroid milieu, although the possibility of 7alpha-hydroxypregnenolone also playing a physiological role cannot be excluded.

The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation.

OBJECTIVE: To evaluate the effect of an aqueous extract of Phyllanthus niruri (Pn), a plant used in folk medicine to treat lithiasis, on the urinary excretion of endogenous inhibitors of lithogenesis, citrate, magnesium and glycosaminoglycans (GAGs). MATERIALS AND METHODS: The effect of chronic (42 days) administration of Pn (1.25 mg/mL/day, orally) was evaluated in a rat model of urolithiasis induced by the introduction of a calcium oxalate (CaOx) seed into the bladder of adult male Wistar rats. The animals were divided into four groups: a sham control (16 rats); a control+Pn (six); CaOx+water instead of Pn (14); and CaOx+Pn (22). Plasma and urine were collected after 42 days of treatment for biochemical analysis and the determination of urinary excretion of citrate, magnesium and GAGs. The animals were then killed and the calculi analysed. RESULTS: The creatinine clearance or urinary and plasma concentrations of Na+, K+, Ca2+, oxalate, phosphate and uric acid were unaffected by Pn or the induction of lithiasis. Treatment with Pn strongly inhibited the growth of the matrix calculus and reduced the number of stone satellites compared with the group receiving water. The calculi were eliminated or dissolved in some treated animals (three of 22). The urinary excretion of citrate and magnesium was unaffected by Pn treatment. However, the mean (sd) urinary concentration of GAGs was significantly lower in rats treated with CaOx+Pn, at 5.64 (0.86) mg/g creatinine, than when treated with CaOx + water, at 11.78 (2.21) mg/g creatinine. In contrast, the content of GAGs in the calculi was higher in the CaOx + Pn rats, at 48.0 (10.4) g/g calculus, than in the CaOx + water group, at 16.6 (9.6) g/g calculus. CONCLUSION: These results show that Pn has an inhibitory effect on crystal growth, which is independent of changes in the urinary excretion of citrate and Mg, but might be related to the higher incorporation of GAGs into the calculi.

[Primary immunodeficiency secondary to ZAP-70 deficiency]. / Imunodeficiência primária por défice de ZAP-70.

The authors present the case of a child with recurrent infections since the age of 4 months, including bilateral pneumonia by Pneumocystis carinii and protracted varicella. Serum immunoglobulin values (when 10 months old), and B cell values were normal. There was persistent lymphocytic leucocytosis, near absence of CD8+ cells, and an increased CD4/CD8 ratio. The percentage of activated T cells and the expression of HLA class I were normal. Proliferation, activation and IL-2 synthesis studies in T cells showed a TCR/CD3-associated signal transduction deficit. ZAP-70 cDNA sequencing showed a mutation, and no ZAP-70 protein was detected in T cells. ZAP-70 deficiency is associated with a rare immune deficiency with absence of CD8+ T cells as well as a functional deficiency in T cells. Seven months after bone marrow transplantation the child is clinically well and immunologically recovered.