Salivary metabolic profile of children and adolescents after hemodialysis

Introduction

The application of metabolomic analysis in the pediatric nephrology field may offer an innovative approach to profile analysis of renal diseases.

Objective

We aimed to analyze the salivary the major metabolites in the saliva of children and adolescents with chronic kidney disease (CKD) before and after hemodialysis.

Method

Thirty-six children diagnosed with CKD and forty healthy children were recruited for the study. ¹H-NMR spectra were analyzed using multivariate and univariate approaches.

Results

The CKD and the healthy control groups presented with similar numbers of dental caries (p?>?0.05) as determined by the number of decayed, missing, or filled deciduous teeth (0.87?±?2.2 and 0.67?±?2.1, respectively) or permanent teeth (0.79?±?1.30 and 0.90?±?1.7, respectively). The amount of dental calculus was significantly higher in the CKD group than in the healthy control group (p?<?0.001). Multivariate analyses using PLS-DA and O-PLS-DA demonstrated differences in the salivary metabolome of CKD patients before and after hemodialysis, as well as between post-dialysis CKD patients and healthy controls, suggesting that HD was not able to recover oral homeostasis. PLS-DA and OPLS-DA models showed satisfactory accuracy (ACC?=?0.72) and prediction (0.64). On multivariate and univariate analyses, urea, acetate, ethanol, and fatty acid were significantly decreased in CKD saliva after hemodialysis. By contrast, saliva from the healthy controls had significantly higher levels of acetate and propionate and lower levels of ethanol, lactate, butyrate, phenylalanine, and creatinine than saliva from post-dialysis CKD patients.

Conclusion

Our results demonstrate that hemodialysis alters the expression of salivary metabolites; however, this alteration does not reestablish the healthy salivary metabolome, as the salivary metabolomic profile of healthy children is significantly different from that of children and adolescents with CKD, both before and after hemodialysis. The unique salivary characteristics of children with CKD may influence their oral health status.

     

Ecological characterization of an ex situ conservation plantation in south‐eastern Mozambique

Mozambican forests are exposed to risks that contribute to the loss of biodiversity and associated ecosystem services. Thus, ex situ conservation represents a key strategy to reduce genetic erosion. In this study, we evaluated the ecological status of the ex situ conservation plantation in Michafutene, Maputo province, one of the most important repositories of forest genetic resources in the country. Thirty plots were established in which all trees, shrubs and grass species were identified. A total of 2092 individuals spanning 39 species were scored. Afzelia quanzensis was the most important species (Importance Value Index – IVI = 203), but with a low silvicultural performance. Other important trees were Albizia adianthifolia (IVI = 32), Albizia versicolor (IVI = 16) and Pterocarpus angolensis (IVI = 12). A complementary genotyping analysis of A. quanzensis was conducted by intersimple sequence repeats, indicating that the germplasm collection has different provenances and represents a wide genetic pool. Thus, despite the poor management, there is a considerable potential for the conservation of A. quanzensis provided immediate and appropriate management activities are implemented to improve its ecological performance.     

Long-Term Follow-up Observation of the Safety,Immunogenicity, and Effectiveness of Gardasil? in Adult Women

Background

Previous analyses from a randomized trial in women aged 24–45 have shown the quadrivalent HPV vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN) and external genital lesions (EGL) related to HPV 6/11/16/18 through 4 years. In this report we present long term follow-up data on the efficacy, safety and immunogenicity of the quadrivalent HPV vaccine in adult women.

Methods

Follow-up data are from a study being conducted in 5 sites in Colombia designed to evaluate the long-term immunogenicity, effectiveness, and safety of the qHPV vaccine in women who were vaccinated at 24 to 45 years of age (in the original vaccine group during the base study [n = 684]) or 29 to 50 years of age (in the original placebo group during the base study [n = 651]). This analysis summarizes data collected as of the year 6 post-vaccination visit relative to day 1 of the base study (median follow-up of 6.26 years) from both the original base study and the Colombian follow-up.

Results

There were no cases of HPV 6/11/16/18-related CIN or EGL during the extended follow-up phase in the per-protocol population. Immunogenicity persists against vaccine-related HPV types, and no evidence of HPV type replacement has been observed. No new serious adverse experiences have been reported.

Conclusions

Vaccination with qHPV vaccine provides generally safe and effective protection from HPV 6-, 11-, 16-, and 18-related genital warts and cervical dysplasia through 6 years following administration to 24–45 year-old women.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00090220","term_id":"NCT00090220"}}NCT00090220     

Nitric Oxide and Brazilian Propolis Combined Accelerates Tissue Repair by Modulating Cell Migration,Cytokine Production and Collagen Deposition in Experimental Leishmaniasis

The fact that drugs currently used in the treatment of Leishmania are highly toxic and associated with acquired resistance has promoted the search for new therapies for treating American tegumentary leishmaniasis (ATL). In this study, BALB/c mice were injected in the hind paw with Leishmania (Leishmania) amazonensis and subsequently treated with a combination of nitric oxide (NO) donor (cis-[Ru(bpy) ₂imN(NO)](PF₆)₃) (Ru-NO), given by intraperitoneal injection, and oral Brazilian propolis for 30 days. Ru-NO reached the center of the lesion and increased the NO level in the injured hind paw without lesion exacerbation. Histological and immunological parameters of chronic inflammation showed that this combined treatment increased the efficacy of macrophages, determined by the decrease in the number of parasitized cells, leading to reduced expression of proinflammatory and tissue damage markers. In addition, these drugs in combination fostered wound healing, enhanced the number of fibroblasts, pro-healing cytokines and induced collagen synthesis at the lesion site. Overall, our findings suggest that the combination of the NO donor Ru-NO and Brazilian propolis alleviates experimental ATL lesions, highlighting a new therapeutic option that can be considered for further in vivo investigations as a candidate for the treatment of cutaneous leishmaniasis.     

Vavraia lutzomyiae n. sp. (Phylum Microspora) infecting the sandfly Lutzomyia longipalpis (Psychodidae, Phlebotominae), a vector of human visceral leishmaniasis

Vavraia lutzomyiae (Microsporida; Pleistophoridae) is a new species parasitic in the tropical phlebotomine sandfly, Lutzomyia longipalpis (Diptera, Psychodidae, Phlebotominae), a major vector of Leishmania chagasi in Latin America where human visceral leishmaniasis is endemic. Infected larvae and pupae were parasitized in the abdomen, and some adults were parasitized in Malpighian tubules and midgut. The sporogonial plasmodium divided by multiple divisions into up to 64 uninucleate sporoblasts. These stages were surrounded outside the plasmalemma by a thick, amorphous dense coat and transformed into a merontogenetic sporophorous vesicle within which the sporonts developed into sporoblasts. The mature microsporidian spores were broadly ellipsoidal and measured 6.1+/-0.43 x 3.1+/-0.15 microm. The spore wall consisted of a transparent endospore (approximately 100 nm) and a thin electron dense exospore (approximately 30 nm) with the outer limit slightly undulated. Spores contained a polar filament arranged peripherally in a single layer of eight to nine wide anterior coils (approximately 125 nm diameter), and three to four narrow posterior coils (approximately 70 nm diameter). Transverse sections revealed a concentric layer organization with the internal layer surrounded by numerous (up to 25) longitudinal microfibrils. The angle of tilt of the polar filament was about 65-68 degrees.     

Brazilian flora extracts as source of novel antileishmanial and antifungal compounds

Natural products have long been providing important drug leads for infectious diseases. Leishmaniasis is a protozoan parasitic disease found mainly in developing countries, and it has toxic therapies with few alternatives. Fungal infections have been the main cause of death in immunocompromised patients and new drugs are urgently needed. In this work, a total of 16 plant species belonging to 11 families, selected on an ethnopharmacological basis, were analyzed in vitro against Leishmania (L.) chagasi, Leishmania (L.) amazonensis, Candida krusei, and C. parapsilosis. Of these plant species, seven showed antifungal activity against C. krusei, five showed antileishmanial activity against L. chagasi and four against L. amazonensis, among them species of genus Plectranthus. Our findings confirm the traditional therapeutic use of these plants in the treatment of infectious and inflammatory disorders and also offer insights into the isolation of active and novel drug prototypes, especially those used against neglected diseases as Leishmaniasis.     

Salivary metabolite signatures of children with and without dental caries lesions

A metabolomic approach was used to analyze endogenous metabolites and to correlate with a specific biological state. The analysis of salivary metabolites is a growing area of investigation with potential for basic and clinical applications. Analyses of children’s saliva in different dentitions and with or without caries could potentially reveal a specific profile related to oral disease risk. Nuclear Magnetic Resonance (NMR) is well suited for mixture analysis followed by Principal Component Analysis combined with Linear Regression (PCA-LR) statistics and was used to identify differences in the salivary metabolites. The classificatory analysis was performed using PCA-LR based on 1,000 cross-validation bootstrap runs from both classifiers in order to increase the data information from a small sample size. The PCA-LR presented a statistically good classificatory performance for children with and without caries with an accuracy of 90.11 % (P < 0.001), 89.61 % sensitivity (P < 0.001), and 90.82 % specificity (P < 0.001). Children with caries lesions presented higher levels of several metabolites, including lactate, fatty acid, acetate and n-butyrate. Saliva from subjects with different dentition stages was also analyzed. Although the salivary samples were poorly classified, permanent dentition presented increased levels of acetate, saccharides and propionate. The NMR data and PCA-LR were able to classify saliva from children with or without caries, with performance indexes comparable to the partial least-squares regression discriminant analysis (PLS-DA) results also performed. Our data also showed similar salivary metabolite profiles for healthy subjects despite the differences in their oral hygiene habits, socioeconomic status and food intake.     

Immunolocalization of stem/progenitor cell biomarkers Oct-4, C-kit and Musashi-1 in endometriotic lesions

Molecular Biology Reports - Human endometrium harbors stem/progenitor cells (SPCs) that may contribute to the establishment of endometriosis when seeded outside the uterus. Oct-4, C-kit and...