[The effect of on-demand glucocorticoid strategy on the occurrence and outcome of p-ALG-associated serum sickness in aplastic anemia].

Objective: To investigate the effect of on-demand glucocorticoid strategy on the occurrence and outcome of porcine anti-lymphocyte globulin (p-ALG) -associated serum sickness in aplastic anemia (AA) . Methods: The data of AA patients who received in the Anemia Diagnosis and Treatment Center of Haematology Hospital, CAMS & PUMC from January 2019 to January 2022 were collected. Among them, 35 patients were enrolled in the on-demand group, with the glucocorticoid strategy adjusted based on the occurrence and severity of serum sickness; 105 patients were recruited in the usual group by matching the age and disease diagnosis according to 1∶3 ratio in patients who received a conventional glucocorticoid strategy in the same period. The incidences, clinical manifestations, treatment outcomes of serum sickness, and glucocorticoid dosage between the two groups were analyzed. Results: The incidences of serum sickness in the on-demand group and the usual group were 65.7% and 54.3% (P=0.237) , respectively. The median onset of serum sickness was the same [12 (9, 13) d vs the 12 (10, 13) d, P=0.552], and clinical symptoms and signs, primarily joint, and/or muscle pain, fever, and rash were similar. Severity grades were both dominated by Grades 1-2 (62.8% vs 51.4%) , with only a few Grade 3 (2.9% vs 2.9%) , and no Grades 4-5. No significant difference in the serum sickness distribution (P=0.530) . The median duration of serum sickness was the same [5 (3, 7) d vs 5 (3, 6) d, P=0.529], and all patients were completely cured after glucocorticoid therapy. In patients without serum sickness, the average dosage of prophylactic glucocorticoid per patient in the usual group was (469.48 ±193.57) mg (0 in the on-demand group) . When compared to the usual group, the average therapeutic glucocorticoid dosage per patient in the on-demand group was significantly lower [ (125.91±77.70) mg vs (653.90±285.56) mg, P<0.001]. Conclusions: In comparison to the usual glucocorticoid strategy, the on-demand treatment strategy could significantly reduce glucocorticoid dosage without increasing the incidence of serum sickness; in addition, the duration of serum sickness and the incidence of above Grade 2-serum sickness were similar.

Prognostic predictors of non-small cell lung cancer treated with curative resection: the role of preoperative CT texture features, clinical features, and laboratory parameters.

AIM: To explore the value of preoperative contrast-enhanced computed tomography (CT) tumour texture characteristics, and clinical and laboratory parameters on the prognosis of curative resection for non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This retrospective study included 64 patients (34 men and 30 women) with NSCLC who underwent curative resection and were then followed up for 5 years or until death. Preoperative contrast-enhanced CT images, clinical features, and laboratory parameters were collected for these patients. CT texture features of the primary tumour before surgery were extracted from the contrast-enhanced CT images using ImageJ software. Based on the cut-off values determined by X-tile software, the preoperative CT texture features, clinical features, and laboratory parameters were divided into two groups. Kaplan-Meier survival curves and log-rank tests were used to compare the 5-year overall survival (OS) of patients. Multivariate Cox regression analysis was used to determine the independent factors influencing the prognosis. RESULTS: The mean survival was 51.5 months. Tumour volume, entropy, platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and albumin-to-globulin ratio (AGR) were shown to be significantly associated with 5-year OS (p<0.05). Multivariate Cox regression analysis revealed that entropy was the independent factor of prognosis (hazard ratio 4.375, 95% confidence interval [CI]: 1.646-11.620, p=0.003). CONCLUSION: Entropy is an important and potentially non-invasive imaging biomarker for predicting the prognosis of NSCLC undergoing curative resection.

Serum protein electrophoresis in Dirofilaria immitis naturally infected dogs: Latest news and a systematic literature review.

According to the main Guidelines on canine heartworm disease (HWD) by the American and European Societies (i.e., AHS, ESDA, and ESCCAP), a correct diagnosis of Dirofilaria immitis infection should include the detection of circulating microfilariae in the whole blood and the adult antigens in serum or plasma sample. So far, scant data are available on laboratory abnormalities in dogs affected by HWD, although techniques including serum protein electrophoresis (SPEP) have proved to be useful for the diagnosis and monitoring of other vector-borne diseases, such as the canine leishmaniosis. Therefore, this study aims to evaluate the SPEP pattern in dogs naturally infected by D. immitis. Furthermore, a systematic review of the literature on this topic was carried out. Medical records from heartworm-positive dogs, of any sex, age, and breed and with available clinical examination and laboratory test results (i.e., complete blood count, serum biochemical profile, and SPEP) were retrospectively collected. If available, laboratory results obtained from dogs after treatment for HWD were also evaluated. When compared with the reference intervals, out of 30 dogs infected by D. immitis and enrolled, 63.3% (n = 19) had a lower percentage of albumin, and 80.0% (n = 24) had higher percentages of beta globulins, with beta-2, and especially beta-3 globulins the most frequently altered fractions. In terms of absolute values (g/dL), the proportion of dogs with hypoalbuminemia, and increased total globulin, alpha, beta- and gamma globulins were 4/30 (13.3%), 6/30 (20.0%), 2/30 (6.7%), 16/30 (53.3%) and 8/30 (26.7%), respectively. For 7 dogs, SPEP results evaluated three and six months after treatment with doxycycline (10 mg/kg BID for 4 weeks) were available. In these dogs a significant post-treatment increase in the percentage of albumin, alpha-2 globulin, and albumin/globulins ratio was observed, as well as a significant decrease both in the percentage and in the absolute value of total-, beta-, and beta-3 globulins. The systematic review of literature databases yielded a total of three studies that were considered eligible and included in the qualitative synthesis. This study provides novel information on SPEP alterations in dogs naturally infected by D. immitis. The evaluation of serum proteins and their electrophoretic pattern may represent an important diagnostic tool for a prompt and accurate diagnosis (e.g., differentiating infections in dogs sharing similar clinical signs and endemic in the same geographical area) and monitoring of HWD.

Potent Anti-SARS-CoV-2 Efficacy of COVID-19 Hyperimmune Globulin from Vaccine-Immunized Plasma.

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.

Predictive Value of Globulin to Prealbumin Ratio for 3-Month Functional Outcomes in Acute Ischemic Stroke Patients.

Objective: We aimed to evaluate and compare the association between globulin to albumin ratio (GAR) and globulin to prealbumin ratio (GPR) and 3-month functional prognosis of acute ischemic stroke (AIS) patients receiving intravenous thrombolysis therapy. Methods: 234 AIS patients undergoing intravenous thrombolysis were retrospectively enrolled with acute ischemic stroke from February 2016 to October 2019. Blood sample was collected within 24 h after admission. Poor outcome was defined as the modified Rankin Scale (mRS) ≥ 3 and a favorable outcome as mRS < 3. Severe stroke was defined as the National Institutes of Health Stroke Scale (NIHSS) score > 10 on admission. Student's t-test, Mann-Whitney U test, Chi-square test, logistics' regression analysis, and receiver operating characteristic (ROC) analysis were performed. Results: Patients with poor functional outcome had higher GAR and GPR levels compared with favorable functional group (p = 0.001, p < 0.001, respectively). Severe stroke was also associated with these two increasing variables. After adjustment for confounding factors, multivariate logistic regression analysis indicated that GPR was an independent indicator predictor of AIS. Conclusions: The 24 h GPR level can predict the 3-month functional outcome in AIS patients accepting recombinant tissue plasminogen activator (r-tPA) intravenous thrombosis.

Comparison of immune reconstitution between anti-T-lymphocyte globulin and posttransplant cyclophosphamide as acute graft-versus-host disease prophylaxis in allogeneic myeloablative peripheral blood stem cell transplantation.

Anti-T-cell lymphocyte globulin (ATLG) and posttransplant cyclophosphamide (PTCy) are now widely used strategies to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Data comparing immune reconstitution (IR) between ATLG and PTCy is scarce. This retrospective study conducted at the University Medical Center Hamburg-Eppendorf (UKE) compares PTCy (n=123) and ATLG (n=476) after myeloablative allogeneic peripheral blood stem cell transplant. Detailed phenotypes of T, B natural killer (NK), natural killer T (NKT) cells were analyzed by multicolor flow at day 30, 100 and 180 posttransplant. Incidence of infections, viral reactivations, GVHD and relapse were collected. Neutrophil engraftment was significantly delayed in the PTCy group (median day 12 vs. day 10, P<0.001) with a high incidence of infection before day+100 in the PTCy arm but a higher Epstein-Barr virus reactivation in the ATLG arm and comparable cytomegalovirus reactivation. Overall incidence of acute GVHD was similar but moderate/severe chronic GVHD was seen more often after PTCy (44% vs. 38%, P=0.005). ATLG resulted in a faster reconstitution of CD8+ T, NK, NKT and gdT cells while CD4 T cells and B cells reconstituted faster after PTCy. Similar reconstitution was observed for T-regulatory cells and B cells. Non-relapse mortality relapse incidence, disease-free survival, and overall survival did not differ significantly between both arms. Even though differences in IR were related to a decreased incidence of infection and moderate/severe cGVHD in the ATLG group they had no impact on any of the other long-term outcomes. However, it remains undetermined which regimen is better as GVHD prophylaxis.

Management of ganciclovir resistance cytomegalovirus infection with CMV hyperimmune globulin and leflunomide in seven cardiothoracic transplant recipients and literature review.

Cytomegalovirus (CMV) disease caused by genetically resistant CMV poses a major challenge in solid organ transplant recipients, and the development of resistance is associated with increased morbidity and mortality. Antiviral resistance affects 5%-12% of patients following ganciclovir (GCV) therapy, but is more common in individuals with specific underlying risk factors. These include the CMV D+R- serostatus, type of transplanted organ, dose and duration of (Val)GCV ([V]GCV) prophylaxis, peak viral loads, and the intensity of immunosuppressive therapy. Guideline recommendations for the management of GCV resistance (GanR) in solid organ transplant recipients are based on expert opinion as there is a lack of data from controlled trials. Second-line options to treat GanR include foscarnet (FOS) and cidofovir (CDV), but these drugs are often poorly tolerated due to high rates of toxicity, such as renal dysfunction and neutropenia. Here, we report seven cardiothoracic transplant recipients with GCV resistance CMV infection from our centre treated with CMV immunoglobulin (CMVIG) +/- leflunomide (LEF) and reviewed the literature on the use of these agents in this therapeutic setting.

Successful Treatment of Steroid-Refractory Checkpoint Inhibitor Myocarditis with Globulin Derived-Therapy: A Case Report and Literature Review.

Immune checkpoint inhibitor (ICI) monoclonal antibody drugs are an important interface of immunology and cancer biology with the intended goal to create cancer specific treatments with less systemic toxicity. Recognition of immune-related adverse events is critical and these include significant cardiovascular toxicity and myocarditis. Compared with other immune-related events, ICI associated myocarditis is rare but is associated with high mortality. The majority of cases present early in the course of therapy and patients can rapidly progress to fulminant myocarditis. Initially, the mainstay of treatment in patients with ICI-associated myocarditis is immunosuppressive therapy with glucocorticoids. For those who do not respond to steroids, the optimal treatment is unclear. This review summarizes the potential adjunctive treatment options for patients with steroid-refractory myocarditis by illustrating a case of myocarditis that was treated with Thymoglobulin and immunoglobulin.

Soy ß-Conglycinin Peptide Attenuates Obesity and Lipid Abnormalities in Obese Model OLETF Rats.

We previously reported that soy ß-conglycinin (ßCG) improves obesity-induced metabolic abnormalities, but not obesity, in obese model Otsuka Long-Evans Tokushima fatty (OLETF) rats. In the present study, we aimed to investigate the effects of ßCG-derived peptide consumption on obesity and lipid abnormality in OLETF rats. To this end, wild-type Long-Evans Tokushima Otsuka and OLETF rats were provided a normal diet containing 20% casein for four weeks as a control. In addition, we prepared ßCG peptide by enzymatic hydrolysis, and OLETF rats were fed a diet in which half of the casein was replaced by ßCG peptide (ßCG peptide group). Consequently, rats in the ßCG peptide group showed decreased abdominal white adipose tissue weight and lipid content (serum and liver triglycerides, and serum and liver cholesterol) compared to control OLETF rats. Further analysis demonstrated that ßCG peptide consumption decreased lipogenic enzyme activity and increased lipolytic enzyme activity in the liver of OLETF rats. In addition, suppressive effects on both synthesis and absorption of cholesterol were observed in ßCG peptide-fed OLETF rats. These findings suggest that peptidization of ßCG enhanced the anti-obese and hypolipidemic effects of ßCG.

Antitimocítica de origen equino en combinación con ciclosporina y corticoide en el tratamiento de pacientes con anemia aplásica severa, sin tratamiento previo, no tributarios a trasplante o postrasplantados no tributarios a segundo trasplante / Antithymocyte of equine origin in combination with cyclosporine and corticosteroid in the treatment of patients with severe aplastic anemia, without prior treatment, not eligible for transplant or post-transplant patients not eligible for a second transplant

INTRODUCCIÓN: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad de globulina antitimocítica de origen equino en el tratamiento de pacientes con anemia aplásica severa sin tratamiento previo y no tributarios a trasplante, o postrasplantados no tributarios a segundo trasplante. La anemia aplásica (AA) es un síndrome autoinmune en la mayoría de los casos idiopáticos, caracterizado por pancitopenia periférica y medula ósea hipocelular, con al menos dos de las siguientes características: 1) Hb < 10 gr/L; 2) Recuento plaquetario < 50 x 109 /L; o 3) Recuento de neutrófilos < 1.5 x 109 /L. La severidad de la AA se determina aplicando los criterios de Camitta y Bacigalupo y está basada en el recuento células sanguíneas en sangre periférica y en los hallazgos en médula ósea. En el mundo, la incidencia de AA se encuentra en un rango entre 0.5 y 4 casos por millón de individuos por año. En el Perú, no se cuenta con estudios de prevalencia o incidencia de AA. El tratamiento de primera línea para pacientes con AA severa es el trasplante alogénico de progenitores hematopoyéticos provenientes de parientes HLA1 idénticos, con el cual las tasas de respuesta son de alrededor del 90 %. En aquellos pacientes en quienes el trasplante no es posible, como por ejemplo los casos en los que no se cuenta con un donante o el paciente es mayor de 50 años, la alternativa de primera línea es la terapia inmunosupresora. La terapia inmunosupresora generalmente recomendada por las guías de práctica clínica (GPC) internacionales y locales incluye globulina antitimocítica (GAT) -de equino o de conejo-, ciclosporina y esteroides. En EsSalud se cuenta en la actualidad con GAT de conejo, ciclosporina, micofenolato y danazol como alternativas de terapia inmunosupresora de primera línea en pacientes con anemia aplásica severa no tributarios a trasplante. No obstante, los especialistas manifiestan que la GAT de origen equino podría ser una mejor alternativa como tratamiento de primera línea para dicha población, por lo que han hecho llegar al IETSI una solicitud de evaluación de GAT de origen equino, en comparación a otras terapias inmunosupresoras, en pacientes con AA severa no tributarios a trasplante. METODOLOGÍA: Se llevó a cabo una búsqueda de la literatura con respecto a la eficacia y seguridad de globulina antitimocítica de origen equino para el tratamiento de anemia aplásica en las bases de datos de PubMed, TRIP y www.clinicaltrials.gov. Adicionalmente, se realizó una búsqueda de evaluaciones de tecnologías y guías de práctica clínica en las páginas web de grupos dedicados a la investigación y educación en salud en general como la National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), Scottish Medicines Consortium (SMC), Instituto de Evaluación de Efectividad Clínica y Sanitaria (IECS), Instituto de Evaluación de Tecnología en Salud (IETS); así como organizaciones especializadas en hematología como American Society of Hematology (ASH), International Society of Hematology (ISH), European Hematology Association (EHA). La estrategia de búsqueda en PubMed se encuentra desarrollada en la Tabla 1 del material suplementario. RESULTADOS: De acuerdo con la pregunta PICO, se llevó a cabo una búsqueda de evidencia científica relacionada al uso de globulina antitimocítica de origen equino en el tratamiento de pacientes con anemia aplásica. En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad (GPC, ETS, RS, MA y ECA). CONCLUSIONES: El presente dictamen preliminar tiene como objetivo evaluar la eficacia y seguridad del uso de GAT de equino en comparación con GAT de conejo, ambos en combinación con ciclosporina, en el tratamiento de pacientes con anemia aplásica severa que no son tributarios a trasplante. La evidencia central para responder a la pregunta PICO del presente dictamen proviene de un ECA de fase II que compara GAT de equino con GAT de conejo, ambas en combinación con ciclosporina y seis GPC internacionales y locales tanto en la población adulta como en la pediátrica. Las GPC incluidas (n=6) son consistentes en recomendar el uso de GAT como terapia inmunosupresora de primera línea de pacientes con AA severa que no son tributarios a trasplante. De las cuales tres recomiendan GAT de equino o conejo indistintamente y las otras tres recomen dan GAT equina por encima de GAT de conejo, y en terapia combinada con ciclosporina A o terapia triple con cliclosporina A y corticoides. El ensayo por Scheinberg et al. identificado responde directamente a la pregunta PICO del presente dictamen al comparar el uso de GAT de equino con GAT de conejo en el tratamiento inmunosupresor de primera línea de pacientes con AA severa. En este se evidencia que GAT de equino es similar a GAT de conejo en términos de SG y que ambos presentan un perfil de seguridad similar, con una tendencia a un mejor perfil por parte de GAT de equino. En conclusión, se tiene que, la evidencia comparativa disponible a la fecha sobre GAT de equino y GAT de conejo proviene de un ECA fase II de calidad moderada, el cual reporta que no hay diferencias en eficacia en términos de SG, ni en el perfil de seguridad entre los medicamentos evaluados. Si bien la evidencia es de calidad moderada, los resultados de una diferencia en 20 puntos porcentuales en la SG a favor de GAT de equino sugieren que, aún en presencia de limitaciones a la validez interna, es probable que GAT de equino sea al menos tan beneficioso como GAT de conejo en términos de SG. Adicionalmente, ambas alternativas terapéuticas son globulinas antitimocíticas, por lo que comparten el mismo mecanismo de acción. Por lo tanto, no se esperaría que estudios posteriores muestren resultados contrarios. Frente a la ausencia de diferencias en eficacia y seguridad entre los fármacos evaluados, cobra relevancia para la toma de decisión el costo de las tecnologías y la inversión que estas representan para la institución. Así, se tiene que, el tratamiento con globulina de origen equino tiene un costo menor al de globulina de conejo, con lo cual su uso supondría a la institución un ahorro entre S/ 3,300 y S/ 42,660 por paciente entre 8 kg y 90 kg, respectivamente. Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI), aprueba el uso de globulina antitimocítica de origen equino como terapia inmunosupresora de primera línea en el tratamiento de anemia aplásica severa en pacientes no tributarios a trasplante. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de nueva evidencia que pueda surgir en el tiempo o al cambio en el mercado peruano de los costos de los productos farmacéuticos comparados.

Structure-function properties of hypolipidemic peptides.

This review addresses the structure-function properties of hypolipidemic peptides. The cholesterol-lowering peptide (lactostatin: IIAEK) operates via a new regulatory pathway in the calcium-channel-related mitogen-activated protein kinase (MAPK) signaling pathway of cholesterol degradation. The bile acid binding peptide (soystatin, VAWWMY) inhibits the micellar solubility of cholesterol in vitro and cholesterol absorption in vivo. VVYP is the most effective peptide having hypotriglyceridemic action in globin digests. The suppressive effect of globin digest on postprandial hyperlipidemia has been reported in humans. The ability of peptides (KRES, Apolipoprotein A-I mimetic peptides) to interact with lipids, remove LOOH and activate antioxidant enzymes associated with high-density lipoprotein determines their anti-inflammatory and anti-atherogenic properties. The ß-conglycinin derived peptides KNPQLR, EITPEKNPQLR, and RKQEEDEDEEQQRE inhibit fatty acid synthase in vitro. These promising findings indicate the need for more conclusive molecular, cellular, and animal and human studies to design innovative new peptides that ameliorate cholesterol and lipid metabolism. PRACTICAL APPLICATIONS: Prevention and amelioration of hypercholesterolemia by dietary regulation are important. Dietary protein and peptides are very useful as regulators of serum cholesterol concentration. Diets low in saturated fat and cholesterol that include soy protein may reduce the risk of heart disease. In Japan, the concept of "food for specified health use" has been introduced for the prevention and treatment of life-style related disease. Thus, peptides derived from food proteins and sources other than food proteins such as peptide-rich functional foods and nutraceutical products, have considerable potential to prevent lifestyle-related diseases, especially hyperlipidemia, as discussed in this review. Furthermore, various strategies have been used for the efficient screening, development, and application of new hypolipidemic peptides. These include the use of phage display (for anti-obesity peptide), peptide mimetics (for anti-atherogenic peptide), and molecular targets such as CYP7A1 (for hypocholesterolemic peptide) and prohibitin (for anti-obesity peptide).

Effective Food Ingredients for Fatty Liver: Soy Protein ß-Conglycinin and Fish Oil.

Obesity is prevalent in modern society because of a lifestyle consisting of high dietary fat and sucrose consumption combined with little exercise. Among the consequences of obesity are the emerging epidemics of hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Sterol regulatory element-binding protein-1c (SREBP-1c) is a transcription factor that stimulates gene expression related to de novo lipogenesis in the liver. In response to a high-fat diet, the expression of peroxisome proliferator-activated receptor (PPAR) γ2, another nuclear receptor, is increased, which leads to the development of NAFLD. ß-Conglycinin, a soy protein, prevents NAFLD induced by diets high in sucrose/fructose or fat by decreasing the expression and function of these nuclear receptors. ß-Conglycinin also improves NAFLD via the same mechanism as for prevention. Fish oil contains n-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid. Fish oil is more effective at preventing NAFLD induced by sucrose/fructose because SREBP-1c activity is inhibited. However, the effect of fish oil on NAFLD induced by fat is controversial because fish oil further increases PPARγ2 expression, depending upon the experimental conditions. Alcohol intake also causes an alcoholic fatty liver, which is induced by increased SREBP-1c and PPARγ2 expression and decreased PPARα expression. ß-Conglycinin and fish oil are effective at preventing alcoholic fatty liver because ß-conglycinin decreases the function of SREBP-1c and PPARγ2, and fish oil decreases the function of SREBP-1c and increases that of PPARα.

Globulina antitimocitica para el tratamiento de anemia aplasica severa adquirida / Antithymocyte globulin for the treatment of acquired severe aplastic anemia

INTRODUCCIÓN: Este documento técnico se realiza a solicitud de la Dirección Ejecutiva del Hospital Regional Lambayeque; la cual motivó la realización de la pregunta PICO por parte de médicos y especialistas de la siguiente manera, P: pacientes con diagnóstico de anemia aplásica (AA) severa adquirida; I: terapia inmunosupresora con globulina antitimocítica equina (hATG) o de conejo (rATG); C: terapia de soporte u otras terapias inmunosupresoras; O: tasa de respuesta hematológica. mortalidad, sobrevida global y libre de eventos, recaídas, calidad de vida, eventos adversos y evolución clonal. OBJETIVO: Describir la evidencia científica disponible sobre la eficacia y seguridad de la ATG en el tratamiento de la AA severa adquirida. METODOLOGÍA: Se realizó una búsqueda sistemática en Medline (Pubmed), The Cochrane Library y LILACS. Ésta se complementó con la búsqueda de evidencia en páginas institucionales de agencias gubernamentales y buscadores genéricos. Se priorizó la identificación y selección de revisiones sistemáticas (RS) con o sin meta-analísis (MA), ensayos clínicos aleatorizados (ECA) o cuasi-experimentales, guías de práctica clínica (GPC), evaluaciones de tecnologías sanitarias (ETS) y evaluaciones económicas de América Latina. La calidad de la evidencia identificada se valoró usando las siguientes herramientas: AMSTAR 2 para la valoración de la calidad de revisiones sistemáticas, la herramienta propuesta por la colaboración Cochrane para la valoración del riesgo de sesgo de ensayos clínicos, y el instrumento AGREE II para valorar el rigor metodológico de las GPC. RESULTADOS: Se identificó dos revisiones sistemáticas (RS), siete ensayos clínicos, dos guías de práctica clínica (GPC) y dos evaluaciones de tecnología sanitaria (ETS) que respondieron a la pregunta PICO de interés. CONCLUSIONES: Las ETS incluidas mostraron resultados discordantes sobre la eficacia y seguridad de ATG. Las GPC incluidas recomiendan hATG como terapia de primera línea en ninõs y adultos sin donante HLA compatible, en pacientes de 35 a 50 anõs, y como alternativa en mayores de 60 años. Las RS incluidas presentaron nievl bajo y criticamente bajo. Los ensayos clínicos tuvieron alto riesgo de sesgo en la mayoria de dimensiones evaluadas. Las GPC incluidas mostraron un puntaje entre 76% y 80% en el rigor metodológico.

The α' subunit of ß-conglycinin and various glycinin subunits of soy are not required to modulate hepatic lipid metabolism in rats.

PURPOSE: This study examined the effect of soy proteins with depletion of different subunits of the two major storage proteins, ß-conglycinin and glycinin, on hepatic lipids and proteins involved in lipid metabolism in rats, since the bioactive component of soy responsible for lipid-lowering is unclear. METHODS: Weanling Sprague Dawley rats were fed diets containing either 20% casein protein in the absence (casein) or presence (casein + ISF) of isoflavones or 20% alcohol-washed soy protein isolate (SPI) or 20% soy protein concentrates derived from a conventional (Haro) or 2 soybean lines lacking the α' subunit of ß-conglycinin and the A1-3 (1TF) or A1-5 (1a) subunits of glycinin. After 8 weeks, the rats were necropsied and liver proteins and lipids were extracted and analysed. RESULTS: The results showed that soy protein diets reduced lipid droplet accumulation and content in the liver compared to casein diets. The soy protein diets also decreased the level of hepatic mature SREBP-1 and FAS in males, with significant decreases in diets 1TF and 1a compared to the casein diets. The effect of the soy protein diets on female hepatic mature SREBP-1, FAS, and HMGCR was confounded since casein + ISF decreased these levels compared to casein alone perhaps muting the decrease by soy protein. A reduction in both phosphorylated and total STAT3 in female livers by ISF may account for the gender difference in mechanism in the regulation and protein expression of the lipid modulators. CONCLUSIONS: Overall, soy protein deficient in the α' subunit of ß-conglycinin and A1-5 subunits of glycinin maintain similar hypolipidemic function compared to the conventional soy protein. The exact bioactive component(s) warrant identification.

Triple terapia inmunosupresora con el empleo del Tymogam® en la aplasia medular idiopática / Immunosuppressive triple-therapy using Tymogam® in idiopathic aplastic anemia

Introducción: la terapia inmunosupresora con globulina antitimocítica o antilinfocítica y ciclosporina A se considera el tratamiento estándar para pacientes con aplasia medular muy severa o severa, que no tienen posibilidades de trasplante de progenitores hematopoyéticos. Objetivo: evaluar la respuesta del tratamiento inmunosupresor con el empleo de Thymogam® en pacientes adultos con aplasia medular idiopática. Método: se realizó un estudio descriptivo de 26 pacientes mayores de 18 años con diagnóstico de aplasia medular idiopática, atendidos en el Instituto de Hematología e Inmunología entre enero del 2000 y abril del 2012, que recibieron como parte del tratamiento inmunosupresor, la globulina antitimocítica (Thymogam®). Resultados: se clasificaron14 pacientes como aplasia medular muy severa y 12 como severa. La media de edad fue de 36 años (rango 18 - 74 años). En los primeros 6 meses después de iniciado el tratamiento, el 73 por ciento alcanzó algún tipo de respuesta y de ellos, en 15 (57,7 por ciento) la respuesta fue completa, la que fue más frecuente en los menores de 25 años. El porcentaje de recaídas fue del 26,3 por ciento. Las reacciones adversas más frecuentes fueron fiebre, hipertensión arterial, temblores y sudoraciones. Las principales complicaciones fueron las hemorragias graves y la sepsis. Un paciente desarrolló una leucemia mieloide aguda. La sobrevida global a los 5 años fue del 73 por ciento. Conclusiones: el Thymogam® es una opción terapéutica viable en el tratamiento inmunosupresor de pacientes con aplasia medular idiopática severa y muy severa(AU)

Introduction: immunosuppressive treatment with antithymocyte or antilymphocyte globulin and cyclosporin A is considered the standard treatment for patients with very severe or severe idiopathic aplastic anemia who do not have the possibility of progenitor hematopoietic transplantation. Objective: to evaluate the responses to immunosuppressive treatment using Thymogam® in adult patients with idiopathic aplastic anemia. Methods: A descriptive study was performed in 26 patients older than 18 years with diagnosis of idiopathic aplastic anemia, attended at the Institute of Hematology and Immunology from January 2000 to April 2012, who received antithymocyte globulin (Thymogam®) as part of immunosuppressive treatment. Results: patients were classified as very severe (14) and severe ( 12). The median age was 36 years old (range 18 - 74 years). In the first six months after the start of treatment, 73 percent of patients obtained some kind of response and 15 of them (57,6 percent) had a complete response, which was more frequent in the group of patients with less of 25 years of age. The percentage of relapse was 26,3 percent. The more frequent adverse reactions were fever, arterial hypertension, tremors and sweatiness. The main adverse reactions were severe bleeding and infections. One patient developed acute myeloid leukemia. Overall survival at 5 years was 73 percent. Conclusion: thymogam® is one therapeutic option in the immunosuppressive treatment in patients with very severe or severe idiopathic aplastic anemia(AU)

Soy ß-conglycinin improves obesity-induced metabolic abnormalities in a rat model of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has a variety of causes including calorie over-intake, an unbalanced diet, and/or genetic dysfunction of lipid metabolism. We hypothesized that NAFLD symptoms could be mitigated by specific nutritional factors. Here, we show that the potential for soy ß-conglycinin (ßCG) to improve obesity-induced metabolic abnormalities in the Otsuka Long Evans Tokushima fatty (OLETF) rat model of NAFLD. Long Evans Tokushima Otsuka (i.e., wild-type) and OLETF rats were provided a normal diet containing 20% casein for 4 weeks as a control. In a third (ßCG) group, OLETF rats were fed a diet in which half of the casein was replaced by ßCG. There was no difference in food intake between groups. Rats in the ßCG group had decreased liver weight and lipid content (triglycerides, cholesterol, and phospholipids) compared to controls. In addition, ßCG consumption decreased fatty acid synthase gene expression and enzymatic activity. These findings indicate that dietary intake of ßCG can improve obesity-induced metabolic dysfunction, possibly via suppression of de novo fatty acid synthesis.

Prevention of osteoporosis by oral administration of phytate-removed and deamidated soybean ß-conglycinin.

Phytate-removed and deamidated soybean ß-conglycinin (PrDS) prepared by ion-exchange resins was supplemented to be 4% in the diet administered to ovariectomized rats to investigate its preventive effect on osteoporosis. The apparent calcium absorption rate decreased following ovariectomy and was not replenished by oral administration of phytate-removed soybean ß-conglycinin (PrS) or casein. On the other hand, administration of PrDS restored the calcium absorption rate to the same level as the sham group. Markers of bone resorption, such as serum parathyroid hormone (PTH) and urinary deoxypyridinoline (DPD), increased, and the bone mineral density and breaking stress decreased following ovariectomy. However, PrDS supplementation suppressed the changes caused by the decrease in calcium absorption from the small intestine. Therefore, PrDS supplementation shows promise for the prevention of postmenopausal osteoporosis.

Soy ß-conglycinin improves glucose uptake in skeletal muscle and ameliorates hepatic insulin resistance in Goto-Kakizaki rats.

Although the underlying mechanism is unclear, ß-conglycinin (ßCG), the major component of soy proteins, regulates blood glucose levels. Here, we hypothesized that consumption of ßCG would normalize blood glucose levels by ameliorating insulin resistance and stimulating glucose uptake in skeletal muscles. To test our hypothesis, we investigated the antidiabetic action of ßCG in spontaneously diabetic Goto-Kakizaki (GK) rats. Our results revealed that plasma adiponectin levels and adiponectin receptor 1 messenger RNA expression in skeletal muscle were higher in ßCG-fed rats than in casein-fed rats. Phosphorylation of adenosine monophosphate-activated protein kinase (AMP kinase) but not phosphatidylinositol-3 kinase was activated in ßCG-fed GK rats. Subsequently, ßCG increased translocation of glucose transporter 4 to the plasma membrane. Unlike the results in skeletal muscle, the increase in adiponectin receptor 1 did not lead to AMP kinase activation in the liver of ßCG-fed rats. The down-regulation of sterol regulatory element-binding factor 1, which is induced by low insulin levels, promoted the increase in hepatic insulin receptor substrate 2 expression. Based on these findings, we concluded that consumption of soy ßCG improves glucose uptake in skeletal muscle via AMP kinase activation and ameliorates hepatic insulin resistance and that these actions may help normalize blood glucose levels in GK rats.

Protective and reparative effects of peptides from soybean ß-conglycinin on mice intestinal mucosa injury.

Peptides derived from alcalase digestion of soybean ß-conglycinin, containing 8.52% carbohydrate, exhibits an inhibition effect on pathogen adhesion or translocation to intestinal cells in vitro. In this study, the protective and reparative effects of ß-conglycinin peptides on intestinal mucosa injury in vivo were studied using mice with dextran sulfate sodium (DSS)-induced intestinal mucosa injury. The results showed that ß-conglycinin peptides contained approximately 21.77% glutamic acid (Glu), and significantly reduced the histological injury in mice both in the protective and reparative experiments. The myeloperoxidase activity of mice treated with ß-conglycinin peptides decreased compared with those treated DSS in the positive control group. Immunohistochemical analysis also showed that ß-conglycinin peptides inhibited the expression of inflammatory factor NF-κB/p65. These results suggested that peptides derived from soybean ß-conglycinin exhibited protective and reparative effects on mice intestinal mucosa injury.

Beneficial effects of ß-conglycinin on renal function and nephrin expression in early streptozotocin-induced diabetic nephropathy rats.

The objective of the present study was to investigate the effects of ß-conglycinin and soya isoflavones on diabetic nephropathy (DN). DN was induced by an intravenous injection of streptozotocin (25 mg/kg) in spontaneously hypertensive rats. DN rats were divided into a non-diabetic group (C, control group) and three DN groups (D, DN with control diet; B, DN+control diet with one-eighth of casein replaced by ß-conglycinin as the protein source; and I, DN+control diet with 0·01 % soya isoflavones). After a 4-week experimental period, we found that fasting blood sugar and plasma and kidney advanced glycation end product levels and 24 h urinary protein excretion of the B group were significantly lower than those of the D group and insulin sensitivity and nephrin expression of the B group were significantly higher than those of the D group. In addition, systolic blood pressure, angiotensin-converting enzyme activity, angiotensin II level and plasma TAG level of the B group were significantly lower than those of the D group, whereas only the levels of plasma TAG and thiobarbituric acid-reactive substances of the I group were lower than those of the D group. In conclusion, ß-conglycinin may be beneficial for retarding DN progression and this effect cannot be completely explained by its isoflavone content.