A Review of the Potential of Chilean Native Berries in the Treatment of Obesity and its Related Features.

Obesity is a major worldwide health threat. It is characterized by an abnormal adipose tissue overgrowth together with increased monocytes infiltration, causing inflammation and oxidative stress, events associated with several illnesses. Investigations have focused on the benefits of native fruit consumption, claiming these to be natural sources of bioactive compounds with antioxidant and anti-inflammatory characteristics. It has been widely stated that berries are a source of the most antioxidant compounds, and, thus, seem highly promising to endure research efforts on these vegetal matrices. The present article describes botanical, chemical and biomedical features of the Chilean native berries, Aristotelia chilensis, Ugni molinae, and Berberis microphylla. This work aims to potentiate incoming research focused on the search for novel treatments for first-order diseases with these particular plant sources.

Collagen type IV-related nephropathies in Portugal: pathogenic COL4A3 and COL4A4 mutations and clinical characterization of 25 families.

Pathogenic mutations in genes COL4A3/COL4A4 are responsible for autosomal Alport syndrome (AS) and thin basement membrane nephropathy (TBMN). We used Sanger sequencing to analyze all exons and splice site regions of COL4A3/COL4A4, in 40 unrelated Portuguese probands with clinical suspicion of AS/TBMN. To assess genotype-phenotype correlations, we compared clinically relevant phenotypes/outcomes between homozygous/compound heterozygous and apparently heterozygous patients. Seventeen novel and four reportedly pathogenic COL4A3/COL4A4 mutations were identified in 62.5% (25/40) of the probands. Regardless of the mutated gene, all patients with ARAS manifested chronic renal failure (CRF) and hearing loss, whereas a minority of the apparently heterozygous patients had CRF or extrarenal symptoms. CRF was diagnosed at a significantly younger age in patients with ARAS. In our families, the occurrence of COL4A3/COL4A4 mutations was higher, while the prevalence of XLAS was lower than expected. Overall, a pathogenic COL4A3/COL4A4/COL4A5 mutation was identified in >50% of patients with fewer than three of the standard diagnostic criteria of AS. With such a population background, simultaneous next-generation sequencing of all three genes may be recommended as the most expedite approach to diagnose collagen IV-related glomerular basement membrane nephropathies.

Collagen type IV-related nephropathies in Portugal: pathogenic COL4A5 mutations and clinical characterization of 22 families.

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.

Comparison of two commercially available ELISAs for circulating sclerostin.

UNLABELLED: This study investigates the performance and correlation of sclerostin measurements by two commercially available sclerostin ELISAs from TECOmedical and Biomedica. We found that the correlation between the results of two sclerostin assays is strong. INTRODUCTION: Circulating sclerostin levels may provide insight into the pathophysiology of metabolic bone diseases such as osteoporosis. However, recent studies suggest that commercially available assays give different results. We compare the analytical performance of the two most used commercially available sclerostin ELISAs from TECOmedical and Biomedica. METHODS: Sclerostin levels were assessed in 20 paired serum, EDTA, and heparin plasma convenience samples from hospitalized patients. In addition, sclerostin was measured in serum samples from 34 patients with metabolic bone diseases and from 10 patients with chronic kidney disease (CKD). Samples from three healthy donors were used to determine stability and intra- and inter- assay precision. RESULTS: The average serum sclerostin concentration of all patients (n = 64) was 0.713 ± 0.58 ng/mL with the Biomedica assay and 0.734 ± 0.43 ng/mL with the TECO assay (p < 0.05). The results correlated strongly (r = 0.9; p < 0.0001), with Passing-Bablok regression showing a linear relationship but with a slight systematic and proportional difference between both assays. Sclerostin levels were about 30% higher in plasma than in serum for both assays, while no significant difference was seen between EDTA and heparin plasma. Intra- and inter- precision were <10% for TECO and <20% for Biomedica. Samples were stable for up to three freeze-thaw cycles with both assays. CONCLUSIONS: The two commercially available ELISAs for measuring circulating levels of sclerostin are comparable. However, given the small but statistically significant systematic and proportional differences between both assays, results and reference ranges will be assay-specific. Results will also be specific to serum or plasma.

Immunoregulatory effects of soluble antigens of Leishmania sp. in human lymphocytes in vitro.

The clinical manifestations of cutaneous leishmaniasis (CL) depend not only on the infecting species involved, but also on the immune response of the individual. Although not yet well understood in humans, parasite survival and persistence are related to the cytokine profile and T cell proliferation, with the Th1 profile being related to cure, and the Th2 profile to disease progression. Considering the need for studies focused on the species with the highest circulation in the state of Amazonas, this study aimed to analyze the immunoregulation stimulated by soluble antigens (SLAs) of Leishmania (L.) amazonensis and Leishmania (V.) guyanensis in human lymphocytes in vitro, in order to understand the immune response of patients with CL. Lymphoproliferation was evaluated against stimuli of SLAs from L. amazonensis (100 µg/mL), SLAs from L. guyanensis (100 µg/mL) and phytohemagglutinin (10 µg/mL) using a BrdU Cell Proliferation ELISA kit after 72 h of incubation. Quantification of the cytokines IL-1b, IL-6, IL-8, IL-10, IL-12 and TNF was performed using the BD™ cytometric bead array human Th1/Th2/Th17 cytokine kit. Our results demonstrated that soluble antigens from L. amazonensis and L. guyanensis stimulated the lymphoproliferation of PBMCs from patients primo-infected with CL. Among the cytokines dosed, the highest concentrations were of IL-6 and IL-8, thus demonstrating that the soluble antigens evaluated are capable of inducing regulatory mechanisms.

Catabolic and anabolic actions of parathyroid hormone on the skeleton.

PTH, an 84-amino acid peptide hormone synthesized by the parathyroid glands, is essential for the maintenance of calcium homeostasis.While in its traditional metabolic role, PTH helps to maintain the serum calcium concentration within narrow, normal limits and participates as a determinant of bone remodeling, more specific actions, described as catabolic and anabolic are also well known. Clinically, the catabolic effect of PTH is best represented by primary hyperparathyroidism (PHPT), while the osteoanabolic effect of PTH is best seen when PTH or its biological amino-terminal fragment [PTH(1-34)] is used as a therapy for osteoporosis. These dual functions of PTH are unmasked under very specific pathological (PHPT) or therapeutic conditions. At the cellular level, PTH favors bone resorption, mostly by affecting the receptor activator of nuclear factor κ-B (RANK) ligand (RANKL)-osteoprotegerin- RANK system, leading to an increase in osteoclast formation and activity. Increased bone formation due to PTH therapy is explained best by its ability to enhance osteoblastogenesis and/or osteoblast survival. The PTH-induced bone formation is mediated, in part, by a decrease in SOST/sclerostin expression in osteocytes. This review focuses on the dual anabolic and catabolic actions of PTH on bone, situations where one is enhanced over the other, and the cellular and molecular mechanisms by which these actions are mediated.

n-3 polyunsaturated fatty acids regulate chemerin in cultured adipocytes: role of GPR120 and derived lipid mediators.

Chemerin is a pro-inflammatory adipokine that is increased in obesity and associated with obesity-related comorbidities. The aim of this study was to investigate the effects of omega-3 polyunsaturated fatty acids, eicosapentaenoic and docosahexaenoic acids (EPA and DHA), on basal and tumor necrosis factor-α (TNF-α)-induced chemerin production in 3T3-L1 and human subcutaneous cultured adipocytes. The potential involvement of G protein-coupled receptor 120 (GPR120), as well as the actions of DHA-derived specialized proresolving lipid mediators (SPMs), resolvin D1 and D2 (RvD1 and RvD2) and maresin 1 (MaR1), were also evaluated. DHA significantly lowered both basal and TNF-α-stimulated chemerin production in 3T3-L1 and human adipocytes. EPA did not modify basal chemerin production, while it attenuated the induction of chemerin by TNF-α. Silencing of GPR120 using siRNA blocked the ability of DHA and EPA to reduce TNF-α-induced chemerin secretion. Interestingly, treatment with the DHA-derived SPMs RvD1, RvD2 and MaR1 also reversed the stimulatory effect of TNF-α on chemerin production in human adipocytes.

Impact of donor age on renal allograft function and survival.

BACKGROUND: The lack of cadaveric donors coupled with a rapidly growing number of potential recipients have stimulated the implementation of several strategies, including the acceptance of older donors, to increase the organ pool and reduce the waiting list for kidney transplantation. However several studies have demonstrated higher incidences of delayed graft function and poor graft outcomes among kidneys harvested from older donors. OBJECTIVE: The objective of this study was to evaluate the influence of donor age on the function and long-term survival of renal allografts. PATIENTS: We performed a retrospective review of the clinical data from 441 adult kidney transplantation from cadaveric heart-beating donors performed in our unit from May 1989 to May 2007. RESULTS: Recipients of kidney allografts from older donors were significantly older (49.2 vs 43.7 years; P < .0001) and had a higher incidence of delayed graft function (15.1% vs 5.4%; P = .005). Renal function was superior following kidney transplantation using younger donors not only at 3 months (P < .0001) and 12 months (P < .0001) posttransplantation, but also upon long-term follow-up at 60 months (P < .0001) and 96 months (P = .030). Allograft survival censored for death with a functioning graft and patient survival were not different when comparing older versus younger donors. Multivariate analysis confirmed the lack of correlation between donor age and allograft failure. CONCLUSION: Donor age showed no influence on allograft survival. However, kidney allografts from older donors displayed lower first year and long-term renal function.

Influence of dialysis duration and modality on kidney transplant outcomes.

BACKGROUND: The influence of pretransplantation dialysis on kidney transplant outcomes has been the subject of longstanding interest. Although increased time on dialysis prior to kidney transplantation is associated with decreased graft and patient survivals, analyses of the impact of dialysis modality on kidney allograft outcome have produced conflicting results. OBJECTIVE: The objective of this study was to evaluate the influence of dialysis duration and modality on the function and survival of renal allografts. PATIENTS: We retrospectively reviewed the clinical data of 421 adults who received first kidney transplantations from cadaveric heart-beating donors performed in our unit from May 1989 to May 2007. Three hundred seventy-four patients (88.8%) were on hemodialysis (HD) prior to kidney transplantation, including 247 patients (58.7%) on treatment for at least 24 months. RESULTS: Patients with a dialysis duration > or =24 months were significantly older (45.9 vs 42.8 years; P = .013). Renal function at 3, 12, 60, and 96 months was similar between the 2 groups. Longer duration on dialysis was associated with poorer overall graft and patient survivals. No differences were observed in renal function or graft and patient survivals comparing HD or peritoneal dialysis (PD). Multivariate analysis confirmed the lack of correlation between dialysis duration or modality and allograft failure. CONCLUSION: Longer dialysis duration influenced overall graft and patient survival. However, dialysis modality showed no influence on graft function or survival.

First year renal function as a predictor of kidney allograft outcome.

BACKGROUND: Several factors are known to have detrimental effects on kidney allograft function in the first year posttransplantation, which has been reported to be an important factor influencing long-term graft survival. OBJECTIVES: The objectives of this study were to evaluate risk factors for lower estimated glomerular filtration rate (eGFR) at 3 and 12 months posttransplantation and analyze the influence of first year allograft function on graft and patient survivals. PATIENTS: We performed a retrospective review of the clinical data from 433 cadaveric donor kidney transplantations in adults performed in our unit from May 1989 to May 2007. RESULTS: Donor female gender and nontraumatic cause of death, panel-reactive antibody (PRA) titer > or =50%, acute rejection episodes, and delayed graft function (DGF) were significant risk factors for a decreased eGFR at one year posttransplantation. Recipient and donor age showed negative correlations with eGFR at 3 and 12 months. A logistic regression model showed acute rejection episodes, DGF, donor age > or =55 years, donor female gender, and nontraumatic cause of donor death to be independent adverse risk factors for eGFR <60 mL/min at 3 and 12 months. Lower eGFRs at 3 and 12 months were associated with poorer allograft survival when data were censored for death with a functioning graft and patient survival. Multivariate analysis revealed that PRA titer > or =50%, acute rejection episodes, and eGFR <30mL/min at 12 months had adverse effects on allograft survival. CONCLUSION: Several factors influence kidney allograft function in the first year after transplantation. Kidney allograft function at 12 months predicted long-term graft survival.

Development of Software for Obtaining Image Attributes for Evaluation of the Wound Healing Process.

The biological process of wound healing is one of the most complex occurrences during our lives turning a serious public health problem. The rate of healing chronic wounds in humans is relatively uniform, regardless of etiologies, and is estimated to be 0.63-0.65 mm/week for diabetics and non- diabetics [1], respectively, being visually unnoticeable throughout the daily care of a wound. A ruler designed for this purpose using a decal for setting the wound limits, however an area with a lot of irregularity requires a tool that carries out this measurement autonomously through image recognition, making the process feasible for the medical teams responsible for the treatment. The digitized images undergo morphological processes sing on the polygonal line that delimits the wound region. With the region delimited by the polygonal, the area and the perimeter are determined. A comparison with analytical methods demonstrates that this tool has the potential to become gold standard for estimating to estimate the area and the perimeter of wounds in the healing process.

Serum Magnesium and Related Factors in Long-Term Renal Transplant Recipients: An Observational Study.

BACKGROUND: Low serum magnesium (MgS) is a known risk factor for cardiovascular and mineral bone disease. In renal transplant recipients (RTRs), low MgS levels have been related to higher glomerular filtration rates (GFR) and with calcineurin inhibitors, particularly tacrolimus. We aimed to evaluate MgS in renal transplant recipients with over 1 year of follow-up to establish related risk factors and the impact of the use of cyclosporine versus tacrolimus. METHODS: Cross-sectional study of 94 RTRs with more than 12 months of follow-up. Hypomagnesemia was defined as serum magnesium level <1.5 mg/dL. RESULTS: Hypomagnesemia was found in 5.3% of patients. MgS showed a negative correlation with creatinine clearance. A positive correlation between MgS with urinary magnesium and phosphorus was found. Cyclosporine versus tacrolimus analysis did not show a significant difference regarding MgS when considering all the population and the subgroup of patients with GFR >45 mL/min/1.73 m2. On the subgroup with GFR <45 mL/min/1.73 m2, those on tacrolimus had lower MgS than those on cyclosporine, but those same patients presented with significantly different GFR, higher in the tacrolimus subgroup. CONCLUSIONS: Hypomagnesemia has a low prevalence in RTRs with more than 1 year of follow-up. MgS levels evidenced a strong correlation with GFR. A significant difference on MgS levels between patients on tacrolimus and cyclosporine was found only when considering GFR <45 mL/min/1.73 m2, in which patients on tacrolimus had significantly higher GFR than patients on cyclosporine, which may explain these results.

Predictive Factors of Acute Rejection in Low Immunologic Risk Kidney Transplant Recipients Receiving Basiliximab.

INTRODUCTION: The optimal immunosuppressive induction therapy in kidney transplant recipients with low immunologic risk of acute rejection (AR) is still controversial. The use of basiliximab (BSX) has led to a significant decrease of AR with a low side effect profile. OBJECTIVE: This study sought to evaluate predictive risk factors for AR in low immunologic risk patients subjected to immunosuppressive induction therapy with BSX. METHODS: We reviewed all low immunologic risk patients (panel reactive antibody [PRA] level <50%, who had undergone a first deceased-donor transplant) subjected to immunosuppressive induction therapy with BSX, calcineurin inhibitor, mycophenolate mofetil, and prednisolone (n = 346). AR was defined as any rejection occurring until 12 months posttransplantation. Predictive risk factors for AR were evaluated by logistic regression and, to find the best cut-off of PRA related to a higher incidence of AR, receiver-operator characteristic (ROC) curve analysis was performed. RESULTS: The rate of AR was 7.8%. Multivariate logistic regression analysis identified age at the time of transplantation (P = .040) and PRA level (P = .001) as independent risk factors for AR. ROC curve analysis confirmed that PRA >10% was related to an increased incidence of AR (19.2% vs 6.0%, P = .005). CONCLUSIONS: A higher incidence of AR was observed in low immunologic risk kidney transplant patients with a PRA level >10%. These data support the use of more intensive immunosuppressive induction therapy in patients with low immunologic risk and a PRA level >10%.

Hyperacute Rejection in a Kidney Transplant With Negative Crossmatch: A Case Report.

Hyperacute rejection (HAR) is a rare event that can be prevented by crossmatch tests that detect anti-human leukocyte antigen antibodies against the donor. We present the case of a 43-year-old man who underwent a deceased-donor kidney transplantation with a negative complement-dependent cytotoxicity and a negative flow cytometry crossmatch. Luminex technology detected anti-DQ donor-specific antibodies (DSA) with a mean fluorescence intensity of 11,000. A single plasmapheresis session was carried out, followed by immunosuppression with immunoglobulin, antithymocyte globulin, tacrolimus, and methylprednisolone. Minutes after graft reperfusion, in the presence of clinical evidence of HAR, the patient underwent nephrectomy. The investigation for the presence of anti-major histocompatibility complex class I-related chain A and anti-endothelial antibodies was negative. This case reinforces the importance of DSA, and more specifically, of anti-DQ DSA in the allogeneic response when detected by solid-phase tests, even with a negative crossmatch, assuming they can be responsible for HAR.

Proton ejection as a major feature of the Ca(2+)-pump.

H+ ejection and Ca2+ uptake promoted by the sarcoplasmic reticulum (SR) Ca(2+)-pump are similarly stimulated by millimolar Mg2+. This cannot be assigned to enhanced Ca2+ uptake and H+ displacement from internal metal binding sites since: (1) loading SR vesicles with high Mg2+ concentrations does not impair H+ ejection; (2) loading SR vesicles with Mn2+ does not depress H+ ejection occurring during Mn2+ uptake; (3) H+ ejection occurs even when Ca2+ accumulation inside the vesicles is prevented with Ca2+ ionophores. It is concluded that the Ca(2+)-pump promotes an active Ca2+/H+ countertransport stimulated by Mg2+. Finally, a mechanism for Ca2+ translocation is proposed in basic physico-chemical terms.

Living kidney donor transplantation: an alternative with limitations.

BACKGROUND: The major issues involved in the decision to donate are the perioperative risk and the risk of chronic kidney disease or even end-stage renal disease. The usual glomerular filtration rate (GFR) in kidney donors after transplantation is approximately 70% of the predonation rate; however, some have a GFR <60 mL/min/1.73 m(2). So after kidney donation, mild to moderate renal insufficiency may occur. Thus, it is important to identify predictor factors of postdonation kidney function. OBJECTIVES: To evaluate the influence of predictor factors in the evolution of the remaining kidney function and to quantify nonpredictable and unexpected developments in GFR at 1 year post donation. METHODS: We performed a study of the evolution of renal function pre- and postnephrectomy of 55 living donors without perioperative comorbidities and a mean follow-up of 6.03 ± 2.7 years. RESULTS: One year after nephrectomy donor function was 32% lower than the prenephrectomy value and 21% of donors had an eGFR <60 mL/min/1.73 m(2). In multivariate logistic regression a living donor with a predonation eGFR <100 but >80 mL/min/1.73 m(2) had 5.24 times a chance of having an eGFR <60 mL/min/1.73 m(2) at 1 year post donation than if he had an eGFR ≥100 mL/min/1.73 m(2). Among 15 donors with prenephrectomy eGFR ≥80 and <100 mL/min/1.73m(2), 8 (53%), RR = 3.26 (1.517-7.012) had eGFR <60 mL/min/ 1.73 m(2). CONCLUSIONS: The eGFR predonation and donor age influenced the first-year postnephrectomy eGFR. Some donors had a more accelerated eGFR fall, not always related to predonation eGFR and age.

Renal transplantation in type 1 diabetes mellitus: an unusual case report.

Diabetes mellitus (DM) may progress to diabetic nephropathy (DN) in approximately 40% of cases and it accounts for one of the most common causes of end-stage of renal disease (ESRD). The pathogenesis of DN involves complex interactions between metabolic and hemodynamic factors. DM type 1 has a dominant impact on morbidity and mortality after renal transplantation. We report a kidney transplantation patient with DM and DN as the etiology of end-stage renal disease and whose post-transplantation evolution over 19 years was remarkably atypical. DM was diagnosed at the age of 7 years and the patient suffered a rapid and aggressive progression of her disease with early development of DN and diabetic retinopathy. Nineteen years post-transplantation, the patient shows neither deterioration of graft function nor clinical reactivation of DN. There seems to be two quite distinct answers to the same injury supported by a group of factors that led to micro- and macrovascular lesions, all present before transplantation and potentially aggravated through some immunosuppressive therapy. This clinical evolution suggests the hypothesis that not only the graft but also the donor may have inherent characteristics that enabled him to display the resistance to DN despite the genetic susceptibility of the receptor. The answers to these questions would help to explain why some patients with diabetes progress to macro- and microvascular complications and others remain resistant to developing these vascular disorders. In this case, the resistance to DN is apparently a feature related to the donor.

Evaluating work experience in the selection of dietary managers.

Because there is such a low correlation between the work experience inventory and examination scores, the work experience inventory may be measuring another dimension of performance. The use of the work experience inventory in conjunction with application forms and employment tests may provide a better indicator of potential performance than any of those methods alone. This concurrent validity study, however, should be followed by predictive validity studies to determine the effectiveness of the work experience inventory in predicting job success of the dietary manager.

An analysis of inservice education practices for hospital laboratory personnel.

Inservice education is a form of continuing professional education provided by the health care employer at the worksite. The purposes of this study were to describe current inservice practices in clinical laboratories and to explore laboratory managers' perceptions of the job impact and cost-worthiness of specific inservice education activities. A written survey was mailed to 237 hospitals in Ohio to gather data. Results of the study (61% usable return) were analyzed using descriptive statistics. Notable findings include: Most laboratories do not have an inservice budget; most important for cost worthiness and job impact are new employee orientation, policy and procedure discussions, and instruction on instrumentation. The report discusses ratings of several inservice activities in terms of their value for improving employees' knowledge, skills, and attitudes.

[Fatal cardiac tamponade in systemic lupus erythematosus associated with vasculitis similar to polyarteritis nodosa]. / Tamponamento cardíaco fatal em portadora de lupus eritematoso sistêmico associado com vasculite semelhante a poliarterite nodosa.

We report the case of a 21 year-old woman who developed systemic lupus erythematosus and fatal cardiac tamponade. Necropsy examination revealed cardiac tamponade as well as other findings of SLE and an unsuspected vasculitis similar to polyarteritis nodosa.