Hypothyroidism and nephrotic syndrome: why, when and how to treat

Hypothyroidism, characterised by low/normal free thyroxine (FT4) and free tri-iodothyronine (FT3) with elevated thyroid-stimulating hormone (TSH), is a well-known complication of nephrotic syndrome (NS). This is a common feature of primary and secondary glomerular diseases and comprises loss of protein in the urine and increased urinary excretion of thyroid hormones and thyroxine-binding globulin. With a normal thyroid reserve, this scenario is associated with the development of subclinical hypothyroidism, with a slight increase in TSH and normal free fractions. However, with a low thyroid reserve the transition toward overt hypothyroidism is almost inevitable, affecting morbidity and mortality. As T4 replacement is a cheap and well-established treatment to achieve a stable hormone status in different types of thyroid deficiency, it is essential to recognise and appropriately treat this condition. In this article we summarise the evidence on this nephro-endocrine disorder in humans and focus on diagnostic and therapeutic strategies

Pharmacological effects of raas blockade in ischemic nephropathy

Background: The management of ischemic nephropathy due to atherosclerotic renal artery stenosis has become increasingly conservative in the modern era, with current guidelines recommending optimized medical therapy as the initial step. The doubts raised by the recently published trials of revascularization strategies have led to a renewed focus on pharmacological strategies promoting blood pressure control and renal protection. It is essential to further elucidate the pathophysiological mechanisms underlying hypoperfusion induced renal microvascular dysfunction with subsequent tissue injury and fibrogenesis. The role of renin angiotensin aldosterone system as a mediator of the main pathophysiological consequences of ischemic nephropathy is well known. However, more recent experimental evidence on the adrenergic system and intrarenal tubular feedback mechanisms has stimulated new interest towards a multi-target therapeutic approach. Methods: This review focuses on the pharmacology of the principle therapeutic drug classes currently used in the treatment of atherosclerotic renal artery stenosis with an analysis of their metabolic aspects and use in clinical practice based on evidence from clinical trials. Results and Conclusions: An optimal pharmacologic approach is crucial for a successful prevention of renal injury and cardiovascular events in this high-risk population. Antihypertensive treatment should include renin angiotensin aldosterone system blockade medication not only for their antihypertensive properties, but especially for those cardio and renoprotectiv

Innovative Biobased and Sustainable Polymer Packaging Solutions for Extending Bread Shelf Life: A Review

bstract: Sustainable packaging has been steadily gaining prominence within the food industry, with biobased materials emerging as a promising substitute for conventional petroleum-derived plastics. This review is dedicated to the examination of innovative biobased materials in the context of bread packaging. It aims to furnish a comprehensive survey of recent discoveries, fundamental properties, and potential applications. Commencing with an examination of the challenges posed by various bread types and the imperative of extending shelf life, the review underscores the beneficial role of biopolymers as internal coatings or external layers in preserving product freshness while upholding structural integrity. Furthermore, the introduction of biocomposites, resulting from the amalgamation of biopolymers with active biomolecules, fortifies barrier properties, thus shielding bread from moisture, oxygen, and external influences. The review also addresses the associated challenges and opportunities in utilizing biobased materials for bread packaging, accentuating the ongoing requirement for research and innovation to create advanced materials that ensure product integrity while diminishing the environmental footprint

MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis

MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD-CD27- memory B-cell population in ACPA+ RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU.1 at B-cell level in the synovial compartment. Stimulation of healthy donor B cells with CD40L, anti-IgM, IL-21, CpG, IFN-α, IL-6 or BAFF induces miR-155 and decreases PU.1 expression. Finally, inhibition of endogenous miR-155 in B cells of RA patients restores PU.1 and reduces production of antibodies. Our data suggest that miR-155 is an important regulator of B-cell activation in RA

Thermal, Mechanical and Micromechanical Analysis of PLA/PBAT/POE-g-GMA Extruded Ternary Blends

In order to toughen Poly(lactic) acid and binary blends with low PBAT content while maintaining a high biodegradability of the final material, poly(lactic) acid (PLA)/poly(butylene-adipate-co-terephthalate) (PBAT)/ polyolefin elastomer grafted with glycidyl methacrylate (POE-g-GMA) extruded ternary blends have been investigated in this work from a thermal, mechanical, and rheological point of view. The two elastomers have been added in different amounts as dispersed phases into the PLA matrix, paying attention to the final objective: the design of a 90% biodegradable formulation according to EN 13432. These ternary blends exhibited improved impact properties but still low elongation at break. Consequently, to the ternary composition with the best compromise of PLA quantity, biodegradability and thermo-mechanical properties (81 wt.% PLA, 9 wt.% PBAT, and 10 wt.% POE-g-GMA) a small quantity (10 wt.%) of a biobased plasticizer was added in order to further increase the impact properties in parallel with the tensile flexibility. Two types of plasticizers were investigated, one not reactive [Acetyl Tributyl Citrate (ATBC)], and one reactive [Glycidyl ether (EJ-400)]. A micromechanical study, in order to investigate the toughening mechanism of these systems, was carried out on the final formulations. They were also examined by dilatometric tests and elasto-plastic fracture mechanics correlating the data obtained to the morphology and to the rheological properties. In conclusion, the best compromise between impact, tensile properties and biodegradability content was achieved using the reactive plasticizer (EJ-400) whose interaction with the matrix is confirmed by the FT-IR analysis

Estudo populacional de síndrome pré-menstrual

OBJECTIVE: To study the prevalence of premenstrual syndrome and the factors associated with this, by comparing the obtained frequency with the self-reported frequency. METHODS:This was a cross-sectional population-based study, involving 1,395 women aged 15 to 49 years old in a medium-sized municipality in Southern Brazil, carried out in 2003. Questionnaires were applied to measure the prevalence of premenstrual syndrome by means of a score based on five premenstrual symptoms that interfered with family life or led to absence from work or school. Associations with socioeconomic, demographic and behavioral variables were investigated. Self-reported syndrome was investigated with regard to its sensitivity and specificity, taking the score as the gold standard. The statistical analyses performed were Pearson chi2, Mantel-Haenszel and Poisson regression, with Kappa coefficients to verify the concordance of the responses. RESULTS: The obtained prevalence was 25.2% (95% CI: 22.5-27.9) and the self-reported prevalence was 60.3% (95% CI: 57.4-63.3). The principal premenstrual symptoms found were: irritability, abdominal discomfort, nervousness, headache, fatigue and breast pain; all of these showed prevalence of over 50%. Higher risk was presented by women of higher socioeconomic level, better schooling level, aged under 30 years and with white skin color. Psychotropic drug users and women who were not using any hormonal contraceptive presented higher prevalence of the syndrome. The sensitivity of the test was 94%, specificity 51% and accuracy 62%. CONCLUSIONS: A high prevalence of premenstrual syndrome was found. Even though the women's perception of the syndrome was higher than the result measured by the symptom score, one quarter of the women presented this health problem.OBJETIVO: Estudar a prevalência e fatores associados à síndrome pré-menstrual, comparando a freqüência encontrada com a auto-referida. MÉTODOS: Foi realizado um estudo transversal, de base populacional, com 1.395 mulheres de 15 a 49 anos no município de Pelotas, Rio Grande do Sul, em 2003. Foram aplicados questionários para medir a prevalência da síndrome pré menstrual por meio de um escore, construído a partir de cinco sintomas pré-menstruais que interferiam na vida familiar ou levavam à falta ao trabalho ou à escola. Foram investigadas associações entre alguns fatores socioeconômicos, demográficos e comportamentais. A síndrome auto-referida foi investigada quanto à sua sensibilidade e especificidade, considerando o escore como padrão-ouro. As análises estatísticas utilizadas foram chi2 de Pearson, Mantel Haenszel e regressão de Poisson, além do coeficiente de Kappa para verificar concordância de respostas. RESULTADOS: A prevalência encontrada foi de 25,2% (IC 95%: 22,5-27,9) e auto-referida 60,3% (IC 95%: 57,4-63,3). Os principais sintomas pré-menstruais foram: irritabilidade, desconforto abdominal, nervosismo, cefaléia, cansaço e mastalgia, todos acima de 50% de prevalência. Mulheres de melhor nível econômico, maior escolaridade, menores de 30 anos e com pele branca apresentaram risco mais elevado. As usuárias de psicofármacos e as que não usavam anticoncepção hormonal apresentaram maior prevalência. A sensibilidade do teste foi de 94%, a especificidade 51% e a acurácia 62%. CONCLUSÕES: Foi alta a prevalência da síndrome pré-menstrual encontrada. Embora a percepção das mulheres seja maior do que aquela medida com o escore, ainda assim, um quarto das mulheres apresentou esse problema de saúde

Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α

In this study, we investigated the bone cell activity in patients with osteogenesis imperfecta (OI) treated and untreated with neridronate. We demonstrated the key role of Dickkopf-1 (DKK1), receptor activator of nuclear factor-κB ligand (RANKL), and tumor necrosis factor alpha (TNF-α) in regulating bone cell of untreated and treated OI subjects. These cytokines could represent new pharmacological targets for OI. Introduction: Bisphosphonates are widely used in the treatment of children with osteogenesis imperfecta (OI) with the objective of reducing the risk of fractures. Although bisphosphonates increase bone mineral density in OI subjects, the effects on fracture incidence are conflicting. The aim of this study was to investigate the mechanisms underlying bone cell activity in subjects with mild untreated forms of OI and in a group of subjects with severe OI treated with cycles of intravenous neridronate. Methods: Sclerostin, DKK1, TNF-α, RANKL, osteoprotegerin (OPG), and bone turnover markers were quantified in serum of 18 OI patients (12 females, mean age 8.86 ± 3.90), 8 of which were receiving cyclic intravenous neridronate, and 21 sex- and age-matched controls. The effects on osteoblastogenesis and OPG expression of media conditioned by the serum of OI patients and anti-DKK1 neutralizing antibody were evaluated. Osteoclastogenesis was assessed in cultures from patients and controls. Results: DKK1 and RANKL levels were significantly increased both in untreated and in treated OI subjects with respect to controls. The serum from patients with high DKK1 levels inhibited both osteoblast differentiation and OPG expression in vitro. High RANKL and low OPG messenger RNA (mRNA) levels were found in lymphomonocytes from patients. High amounts of TNF-α were expressed by monocytes, and an elevated percentage of circulating CD11b-CD51/CD61+ osteoclast precursors was observed in patients. Conclusions: Our study demonstrated the key role of DKK1, RANKL, and TNF-α in regulating bone cell activity of subjects with OI untreated and treated with bisphosphonates. These cytokines could represent new pharmacological targets for OI patients

Chemerin and PEDF are metaflammation-related biomarkers of disease activity and obesity in rheumatoid arthritis

Objective: Obesity is a risk factor for Rheumatoid Arthritis (RA) being associated to low grade inflammation. This study aimed to determine whether PEDF and Chemerin are biomarkers of inflammation related to fat accumulation in RA and to investigate whether weight loss associates with clinical disease improvement through the modification of fat-related biomarkers in overweight/obese RA with low-moderate disease. Participants and Methods: Two-hundred and thirty RA patients were enrolled, of whom 176 at disease onset treated according to a treat-to-target strategy (T2T) and 54 overweight/obese RA in stable therapy and low-moderate disease activity. Gene expression of adipokines, interleukin-6 and their receptors were examined in adipose tissue from obese RA. Obese RA with low-moderate disease activity underwent low-calories diet aiming to Body Mass Index (BMI) reduction > 5%, maintaining RA therapy unchanged. Chemerin, PEDF and Interleukin-6 plasma values were assessed by ELISA and disease activity was evaluated. Results: At RA onset, PEDF and Chemerin plasma values correlated with BMI (p < 0.001) but only Chemerin plasma values correlated with disease activity (p < 0.001). After adopting a T2T strategy, Chemerin arose as an independent factor associated with remission in early RA [OR(95%CIs):0.49(0.25-0.97)]. Moreover, after low-calories diet, RA with low-moderate disease activity reaching BMI reduction 655% (62.6%) at 6 months had significant decrease of PEDF (p < 0.05) and Chemerin (p < 0.05) plasma values, in parallel with the improvement in disease activity. Conclusions: PEDF and Chemerin arose as biomarkers of obesity and metaflammation respectively, providing a link between chronic inflammation and excess of body weight in RA. Therefore, BMI reduction of at least 5% in obese RA allowed better disease control without modifying RA treatment