Fernando Capela e Silva

Prognostic Factors of Chronic Graft-versus-Host Disease Following Allogeneic Peripheral Blood Stem Cell Transplantation: The National Institutes Health Scale Plus the Type of Onset Can Predict Survival Rates and the Duration of Immunosuppressive Therapy

Several grading systems have been developed in the bone marrow transplantation setting in attempts to predict survival in patients with chronic graft-versus-host disease (cGVHD). In this study, we evaluated the prognostic value of the National Institutes of Health (NIH) scoring system and investigated for any additional prognostic factors in a series of 171 patients undergoing peripheral blood stem cell transplantation (PBSCT) from matched related donors. The cumulative incidence of cGVHD was 70%; cumulative incidences of mild, moderate, and severe cGVHD were 29%, 42% and 28%, respectively. Overall, 68% of patients were free from immunosuppression 5 years after transplantation. Absence of previous acute GVHD (aGVHD; hazard ratio [HR] = 2; P = .004) and mild cGVHD (HR = 4.2; P = .007) increased the probability of being off immunosuppressive treatment by the last follow-up. Overall survival (OS) at 5 years was 52%. Severe cGVHD, according to the NIH scoring system (HR = 13.27; P = .001) adversely influenced outcome, whereas de novo onset (HR = 0.094; P = .003) had a more favorable impact on survival. The combination of both variables allowed us to identify 4 different subgroups of patients with OS of 82%, 70%, 50%, and 25%. Our findings indicate that the NIH scoring system has some prognostic value in patients undergoing PBSCT and, together with the type of onset, must be considered to predict the possible outcome of patients who develop cGVHD.

Changes in mouse whole saliva soluble proteome induced by tannin-enriched diet

BackgroundPrevious studies suggested that dietary tannin ingestion may induce changes in mouse salivary proteins in addition to the primarily studied proline-rich proteins (PRPs). The aim of the present study was to determine the protein expression changes induced by condensed tannin intake on the fraction of mouse whole salivary proteins that are unable to form insoluble tannin-protein complexes. Two-dimensional polyacrylamide gel electrophoresis protein separation was used, followed by protein identification by mass spectrometry.ResultsFifty-seven protein spots were excised from control group gels, and 21 different proteins were identified. With tannin consumption, the expression levels of one α-amylase isoform and one unidentified protein increased, whereas acidic mammalian chitinase and Muc10 decreased. Additionally, two basic spots that stained pink with Coomassie Brilliant Blue R-250 were newly observed, suggesting that some induced PRPs may remain uncomplexed or form soluble complexes with tannins.ConclusionThis proteomic analysis provides evidence that other salivary proteins, in addition to tannin-precipitating proteins, are affected by tannin ingestion. Changes in the expression levels of the acidic mammalian chitinase precursor and in one of the 14 salivary α-amylase isoforms underscores the need to further investigate their role in tannin ingestion.

A new piezoelectric actuator induces bone formation in vivo: A preliminary study

This in vivo study presents the preliminary results of the use of a novel piezoelectric actuator for orthopedic application. The innovative use of the converse piezoelectric effect to mechanically stimulate bone was achieved with polyvinylidene fluoride actuators implanted in osteotomy cuts in sheep femur and tibia. The biological response around the osteotomies was assessed through histology and histomorphometry in nondecalcified sections and histochemistry and immunohistochemistry in decalcified sections, namely, through Massons trichrome, and labeling of osteopontin, proliferating cell nuclear antigen, and tartrate-resistant acid phosphatase. After one-month implantation, total bone area and new bone area were significantly higher around actuators when compared to static controls. Bone deposition rate was also significantly higher in the mechanically stimulated areas. In these areas, osteopontin increased expression was observed. The present in vivo study suggests that piezoelectric materials and the converse piezoelectric effect may be used to effectively stimulate bone growth.

Effects of high-fat diet on salivary α-amylase, serum parameters and food consumption in rats

Salivary α-amylase, a major protein in saliva, has been described as a marker of sympathetic nervous system activity, hence for metabolic energy balance. In this context, its expression in overweight and obesity is of interest. Rats fed with a diet enriched with sunflower oil differentially gained weight yielding two subgroups according to their susceptibility (OP) or resistance (OR) to obesity. Elevated plasmatic levels of leptin in the OP subgroup and altered plasmatic lipid profiles (lower triglycerides and higher total cholesterol/high-density lipoprotein (HDL) ratio compared to controls) in the OR subgroup were observed. Animals from the OP subgroup presented higher α-amylase expression and activity even prior to the dietary treatment, suggesting that this salivary protein may constitute a putative indicator of susceptibility for fat tissue accumulation. After 18 weeks of high-fat diet consumption, salivary α-amylase levels did not significantly change in the OP subgroup, but increased 3-fold in the OR subgroup. The increase in α-amylase levels for the latter might represent an adaptation to lower starch intake. These results suggest that salivary α-amylase secretion might be useful to predict susceptibility for weight gain induced by high-fat diet consumption.

The Effect of Tannins on Mediterranean Ruminant Ingestive Behavior: The Role of the Oral Cavity

Sheep, cattle and goat are domestic ruminants of significant economic interest in the Mediterranean region. Although sharing the same pasture ranges, they ingest different plants and plant parts and, consequently different levels of tannins. This suggests an ability to detect and adapt ingestion according to animal physiological limits of tolerance for plant secondary metabolites. This review will detail the effects of dietary tannins on feeding behavior, and the role of the oral cavity in this process, with focus on such ruminant species. The role of salivary protein profile in tannin perception in the oral cavity, and as a defense mechanism, will be discussed.

Assessing foraging strategies of herbivores in Mediterranean oak woodlands: a review of key issues and selected methodologies

Montados are agro-silvo-pastoral ecosystems, typical of the Southwest Iberian Peninsula, of high socio-economic and conservation importance, where grazing is a dominant activity. Montados are characterized by an open tree canopy of Quercus sp. and a diverse undercover of shrubs and grasslands that constitute the plant food resources for grazing animals. Plant food resources of Montados are highly variable, both spatially and seasonally, in quantity and quality. Reliable and easy to use methods to monitor grazing are necessary to allow proper understanding of foraging strategies of grazing animals and to set sustainable grazing management. We describe the main characteristics of the plant food resources available for grazing animals, striking its variability, and revise the potential of using N-alkanes and saliva proteome methods to assess foraging strategies in Montados. In a scenario of dynamic multiple choices, we discuss the use of n-alkane methodology for the simultaneous estimation of diet composition and voluntary intake and saliva proteome as a mean of increasing the knowledge on diet adjustments.

Effect of vitamin D treatment in chronic GVHD

Currently, there is no standard approach for patients with chronic GVHD (cGVHD) who do not respond to or who relapse after first-line treatment, and rescue therapy is based on immunosuppressive drugs and glucocorticoids, which are responsible for the development of severe complications. Vitamin D (Vit D) has a potent immunomodulatory effect, as shown in vitro and in animal models, nevertheless there is no information about its use in the the cGVHD setting. We evaluated retrospectively the outcome of cGVHD in a series of 12 patients receiving vit D because of proved osteopenia or osteoporosis by bone densitometry after allo-HSCT. These patients also had active cGVHD at the time when vit D treatment was started. We observed a marked improvement in cGVHD for most of these patients, without appreciable secondary effects. Chronic GVHD was classified as limited versus extensive, and also the National Institutes of Health scoring system was used, based on the data collected from the medical files of the patients. The first-line treatment for cGVHD was CsA or tacrolimus plus prednisone at 1mg/kg per day, which was switched to alternating days after 4 weeks of treatment. Patient characteristics are summarized in Table 1. According to our standard procedures, patients undergoing allo-HSCT have a bone densitometry performed between 6 months and 1 year after transplantation to rule out osteopenia or osteoporosis. In case it is detected, then a dosage of vit D 1000 IU per day (oral) plus calcium carbonate 1250mg (one pill per os daily) are prescribed for at least 6 months. Chronic GVHD response was assessed according to National Institutes of Health response criteria at 3 and 6 months after the beginning of vit D plus calcium treatment. For skin involvement, a PR was considered to have occurred when at least 50% of the skin involvement appeared to be non-inflammatory or to be fixed, and for complete response, as either the disappearance of all lesions or the presence of fixed and pigmented lesions. Chronic GVHD was diagnosed at a median day of 147 after transplant (range: 119–491 days). At the time when vit D treatment was started, six patients had received one line of immunosuppressive treatment, three patients had received two lines of treatment, two patients had received three lines and one patient had received four lines of treatment. Seven patients had mild, two patients had moderate and three had severe cGVHD; organ involvement is summarized in Table 2. At 3 months after vit D treatment, three patients obtained complete response, six patients obtained PR and one patient had no response, with six patients displaying mild and one patient showing severe cGVHD. Finally, at 6 months after treatment, five patients obtained complete response, six patients obtained PR and one patient had no response, with six patients displaying mild and one of them showing moderate cGVHD. No immunosuppressive drugs were added to the treatment during this period. Interestingly, at the beginning of vit D treatment, 10 patients were receiving calcineurin inhibitors, one patient was receiving calcineurin inhibitor plus prednisone and one patient was receiving mofetil mycophenolate plus prednisone. After 6 months of vit D treatment, five patients were not receiving immunosuppressive drugs, whereas seven patients were receiving immunosuppressive treatment based on CsA or tacrolimus (with or without topical treatment in five patients and with other systemic immunosuppressive drug in two patients). We compared patients who received vit D and who had not previously relapsed (n1⁄4 6) with a cohort of 24 patients, transplanted during the same period of time, who had not received vit D and were on first-line treatment for cGVHD, and had similar characteristics regarding GVHD severity and extension. Interestingly, 50% of the patients receiving vit D were put off on immunosuppresion for 6 months after

[Is it Fabry Disease? Diagnostic and Follow-Up Approach].

1. Serviço de Nefrologia. Centro Hospitalar do Porto. Porto. Portugal. 2. ICBAS, Instituto de Ciências Biomédicas Abel Salazar. Porto. Portugal. 3. Serviço de Nefrologia. Centro Hospitalar do Algarve. Faro. Portugal. 4. Serviço de Cardiologia. Centro Hospitalar do Médio Ave. Santo Tirso. Portugal. 5. Serviço de Neurologia. Centro Hospitalar Universitário de Coimbra. Coimbra. Portugal. 6. Serviço de Medicina 1. Hospital de Santa Maria. Centro Hospitalar Lisboa Norte. Lisboa. Portugal. 7. Serviço de Nefrologia. Centro Hospitalar de Vila Nova de Gaia/Espinho. Vila Nova de Gaia. Portugal.  Autor correspondente: Idalina Beirão. idalina.m.b@gmail.com Recebido: 31 de março de 2015 Aceite: 17 de agosto de 2015 | Copyright

Detection of 70 kDa heat shock protein in the saliva of dairy cows.

This Research Communication describes, for the first time, the detection of HSP70 in saliva of dairy cows. Thermal stress is a major environmental stress that limits animal growth, metabolism, and productivity. The cellular response to heat stress involves the synthesis of heat shock proteins (HSPs), presumably to protect the functional stability of cells at increasing temperatures. HSP70 has been found to be present in cattle blood serum and may also be present in other secretory fluids, such as saliva, as already observed in humans. The aim of this study was to detect heat shock protein HSP70 in bovine saliva. Saliva samples were taken from higher- (n = 5) and lower milk producing (n = 5) Holstein-Friesian cows in summer and in winter for the detection of HSP70. HSP70 concentrations were assayed using the ELISA technique. Salivary HSP70 concentrations ranged from 0·524 to 12·174 ng/ml in cows. Higher salivary HSP70 concentrations were significantly associated with higher milk production and higher environmental temperature, but not with rectal temperature.

Biomarkers and Imaging Findings of Anderson–Fabry Disease—What We Know Now

Anderson–Fabry disease (AFD) is an X-linked lysosomal storage disorder, caused by deficiency or absence of the alpha-galactosidase A activity, with a consequent glycosphingolipid accumulation. Biomarkers and imaging findings may be useful for diagnosis, identification of an organ involvement, therapy monitoring and prognosis. The aim of this article is to review the current available literature on biomarkers and imaging findings of AFD patients. An extensive bibliographic review from PubMed, Medline and Clinical Key databases was performed by a group of experts from nephrology, neurology, genetics, cardiology and internal medicine, aiming for consensus. Lyso-GB3 is a valuable biomarker to establish the diagnosis. Proteinuria and creatinine are the most valuable to detect renal damage. Troponin I and high-sensitivity assays for cardiac troponin T can identify patients with cardiac lesions, but new techniques of cardiac imaging are essential to detect incipient damage. Specific cerebrovascular imaging findings are present in AFD patients. Techniques as metabolomics and proteomics have been developed in order to find an AFD fingerprint. Lyso-GB3 is important for evaluating the pathogenic mutations and monitoring the response to treatment. Many biomarkers can detect renal, cardiac and cerebrovascular involvement, but none of these have proved to be important to monitoring the response to treatment. Imaging features are preferred in order to find cardiac and cerebrovascular compromise in AFD patients.