Advanced glycation end products of dietary origin and their association with inflammation in diabetes - A minireview.

Advanced glycation end products (AGEs) are a diverse group of compounds that are formed as a result of the non-enzymatic reaction between a reducing sugar such as glucose and the free NH2 groups of an amino acid in a protein or other biomolecule. The chemical reaction, by which these products are generated, is known as the Maillard reaction and occurs as a part of the body's normal metabolism. Such a reaction is enhanced during diabetes due to hyperglycemia, but it can also occur during the preparation, processing, and preservation of certain foods. Therefore, AGEs can also be obtained from the diet (d-AGE) and contribute to an increase of the total serum pool of these compounds. They have been implicated in a wide variety of pathological processes, mainly because of their ability to induce inflammatory responses and oxidative stress increase. They are extensively accumulated as a part of the normal aging, especially in tissues rich in long half-life proteins, which can compromise the physiology of these tissues. d-AGEs are abundant in diets rich in processed fats and sugars. This review is addressed to the current knowledge on these products and their impact on the immunomodulation of various mechanisms that may contribute to exacerbation of the diabetes pathophysiology.

Possible role of metformin as an antidepressant in diabetes.

OBJECTIVE: Metformin (MET) is a drug used in the treatment of type 2 diabetes due to its insulin receptor sensitizing properties and anti-hepatic gluconeogenesis effect. One of the comorbidities in diabetes is the depression. This review aimed at summarizing the results of the available MET, depression and diabetes studies to clarify the possible role of MET in the depression during diabetes. METHODS: A bibliographic search on PubMed, Embase, PsycINFO, Web of Science, Cochrane Central for studies referring to MET, depression and diabetes. RESULTS: Several studies have associated depression to the chronic inflammation that characterizes diabetes. Additionally MET is an anti-inflammatory molecule that generally acts by activating AMPK and inhibiting the NF-kB factor. In the context of diabetes, MET can act directly as an anti-inflammatory drug as well as inhibiting other pro-inflammatory molecules. In this regard, MET may inhibit the pro-inflammatory effects of angiotensin II. By facilitating the action of insulin and reducing hepatic gluconeogenesis, MET reduces circulating glucose levels, decreasing the formation of advanced glycation end products and therefore inflammation. During diabetes, the gut microbiota and the permeability of the intestinal barrier are altered, causing high levels of circulating lipopolysaccharides (LPS), which induce inflammation. MET can normalize the microbiota and the intestinal barrier permeability reducing the levels of LPS and inflammation. Clinical and experimental studies show the anti-depressant effect of MET mediated by different mechanisms both at the peripheral level and in the central nervous system. CONCLUSION: Therefore, MET as an anti-inflammatory drug can decrease symptoms of depression and represents a therapeutic approach to improve the psychological state of patients with diabetes. Additionally, insulin also has an anti-inflammatory effect that could act together with MET.

Angiotensin II and post-streptococcal glomerulonephritis.

BACKGROUND: Post-streptococcal glomerulonephritis (PSGN) is a consequence of the infection by group A beta-hemolytic streptococcus. During this infection, various immunological processes generated by streptococcal antigens are triggered, such as the induction of antibodies and immune complexes. This activation of the immune system involves both innate and acquired immunity. The immunological events that occur at the renal level lead to kidney damage with chronic renal failure as well as resolution of the pathological process (in most cases). Angiotensin II (Ang II) is a molecule with vasopressor and pro-inflammatory capacities, being an important factor in various inflammatory processes. During PSGN some events are defined that make Ang II conceivable as a molecule involved in the inflammatory processes during the disease. CONCLUSION: This review is focused on defining which reported events would be related to the presence of this hormone in PSGN.

Apoptosis in post-streptococcal glomerulonephritis and mechanisms for failed of inflammation resolution.

Post-streptococcal glomerulonephritis is a condition resulting from infection by group A beta-hemolytic streptococcus. The main mechanism involves the formation of immune complexes formed in the circulation or in situ on the glomerular basement membrane, which activates complement and causes various inflammatory processes. Cellular mechanisms have been reported in the induction of kidney damage represented by the infiltration of innate cells (neutrophils and monocyte/macrophages) and adaptive cells (CD4 + lymphocytes and CD8 + lymphocytes) of the immune system. These cells induce kidney damage through various mechanisms. It has been reported that nephritogenic antigens are capable of inducing inflammatory processes early, even before the formation of immune complexes. Usually, this disease progresses towards clinical and renal normalization; however, in a smaller number of patients, it evolves into chronicity and persistent kidney damage. Hypotheses have been proposed regarding the mechanisms underlying this progression to chronicity including failure to induce apoptosis and failure to phagocytose apoptotic cells, allowing these cells to undergo membrane permeabilization and release pro-inflammatory molecules into the environment, thereby perpetuating renal inflammation. Other mechanisms involved include persistent infection, genetic background of the host's complement system, tubulointerstitial changes, and pre-existing kidney damage due to old age and comorbidities.

Angiotensin II and dengue.

Dengue is a disease caused by a flavivirus that is transmitted principally by the bite of an Aedes aegypti mosquito and represents a major public-health problem. Many studies have been carried out to identify soluble factors that are involved in the pathogenesis of this infection. Cytokines, soluble factors, and oxidative stress have been reported to be involved in the development of severe disease. Angiotensin II (Ang II) is a hormone with the ability to induce the production of cytokines and soluble factors related to the inflammatory processes and coagulation disorders observed in dengue. However, a direct involvement of Ang II in this disease has not been demonstrated. This review primarily summarizes the pathophysiology of dengue, the role of Ang II in various diseases, and reports that are highly suggestive of the involvement of this hormone in dengue.

Angiotensin II and human obesity. A narrative review of the pathogenesis / Angiotensina II y obesidad humana. Revisión narrativa de la patogénesis

Abstract Angiotensin II (Ang II) is a hormone and the main effector of the renin-angiotensin system (RAS). This peptide has crucial pathophysiological effects on hypertension, cardiac hypertrophy, endothelial proliferation, inflammation and tissue remodelling through G protein-coupled receptors. The pro-inflammatory role of Ang II has been reported in various inflammatory processes. Obesity is linked to a chronic inflammatory process which in turn is the cause of some of its morbidities. Ang II is related to the comorbidities related to the comorbidities of obesity, which include alterations in the heart, kidney, hypertension and coagulation. In this regard, activation of AT1 receptors by Ang II can induce an inflammatory process mediated by the transcription factor NF-kB, triggering inflammation in various systems that are related to the comorbidities observed in obesity. The aim of this review was to highlight the pro-inflammatory effects of Ang II and the alterations induced by this hormone in various organs and systems in obesity. The search was done since 1990 through Medline, EMBASE and PubMed, using the keywords: angiotensin II; angiotensin II, obesity; angiotensin II, kidney, obesity; angiotensin II, coagulation, obesity; angiotensin II, inflammation, obesity; angiotensin II, adipose tissue, obesity; angiotensin II, hypertension, obesity; angiotensin II, insulin resistance, obesity; angiotensin II, adiponectin, leptin, obesity; angiotensin II, COVID-19, obesity. Angiotensin II through its interaction with its AT1 receptor, can induce alterations in diverse systems that are related to the comorbidities observed in obesity. Therapeutic strategies to decrease the production and action of Ang II could improve the clinical conditions in individuals with obesity.

Resumen La angiotensina II (Ang II) es una hormona y el principal efector del sistema renina-angiotensina (SRA). Este péptido tiene importantes efectos fisiopatológicos en la hipertensión, la hipertrofia cardíaca, la proliferación endotelial, la inflamación y la remodelación tisular a través de receptores acoplados a la proteína G. El papel pro-inflamatorio de la Ang II se ha reportado en diversos procesos inflamatorios. La obesidad está ligada a un proceso inflamatorio crónico que a su vez es causa de algunas de sus morbilidades. Se ha demostrado que la Ang II está relacionada con las comorbilidades de la obesidad, que incluyen alteraciones en el corazón, el riñón, la hipertensión y la coagulación. En este sentido, la activación de los receptores AT1 por la Ang II puede inducir un proceso inflamatorio mediado por el factor de transcripción NFkB desencadenado inflamación en diversos sistemas que se relacionan con las co-morbilidades observadas en la obesidad. El propósito de esta revisión fue destacar el efecto pro-inflamatorio de la Ang II y las alteraciones inducidas por esta hormona en diversos órganos y sistemas en la obesidad. La búsqueda se hizo desde 1990 a través de Medline, EMBASE and PubMed, utilizando las palabras clave: angiotensina II; angiotensina II, obesidad; angiotensina II, riñón, obesidad; angiotensina II, coagulación, obesidad; angiotensina II, inflamación, obesidad; angiotensin II, adipose tissue, obesidad; angiotensin II, hipertensión, obesidad; angiotensin II, resistencia a la insulina, obesidad; angiotensin II, adiponectina, leptina, obesidad; angiotensina II, COVID-19, obesidad. La angiotensina II a través de su interacción con su receptor AT1 puede inducir alteraciones en diversos sistemas que están relacionados con las comorbilidades observadas en la obesidad. Estrategias terapeúticas para disminuir su producción y la acción de la AngII pudieran mejorar las condiciones clínicas en individuos con obesidad.

Prevalencia de hipotiroidismo subclínico y biomarcadores de riesgo cardiovascular en pacientes del Hospital General de Riobamba / Prevalence of subclinical hypothyroidism and biomarkers of cardiovascular risk in patients of the General Hospital of Riobamba

El Hipotiroidismo subclínico (HSC) es definido bioquímicamente por una elevación en la concentración sérica de la hormona TSH con niveles normales de T4 libre. El objetivo de este estudio fue determinar la prevalencia de HSC en los pacientes que asistieron a la consulta de medicina interna del Hospital General IESS de Riobamba. Así como, analizar la correlación entre los parámetros hormonales y ciertos marcadores bioquímicos asociados con el incremento de riesgo cardiovascular. Se realizó una investigación de tipo descriptiva, observacional, con un diseño no experimental de corte transversal, que abarcó el periodo comprendido desde enero de 2019 hasta septiembre de 2021. 245 pacientes fueron diagnosticados con HSC, lo cual representó el 10.58 % del universo poblacional estudiado, 61.2% eran del sexo femenino, mientras que el 38.8% del sexo masculino. El mayor número de casos (59.61 %) se observó en el grupo etario mayor de 65 años, distribuidos de la siguiente manera: (22.86% hombres y 36.75% mujeres), también se encontró que el HSC está asociado con un perfil lipídico aterogénico, caracterizado por un incremento en la concentración de colesterol total y LDL los cuales se correlacionaron positivamente con las concentraciones de TSH.

Subclinical hypothyroidism (SH) is biochemically defined by an elevation in the serum concentration of TSH hormone with normal levels of free T4. The aim of this study was to determine the prevalence of SH in patients attending the internal medicine clinic of the General Hospital IESS of Riobamba. Also, to analyze the correlation between hormonal parameters and certain biochemical markers associated with increased cardiovascular risk. A descriptive, observational, non-experimental cross-sectional design was performed, covering the period from January 2019 to September 2021. 245 patients were diagnosed with SH, which represented 10.58 % of the population universe studied, 61.2% were female, while 38.8% were male. The highest number of cases (59.61 %) was observed in the age group over 65 years, distributed as follows: (22.86% men and 36.75% women), it was also found that SH is associated with an atherogenic lipid profile, characterized by an increase in the concentration of total cholesterol and LDL which correlated positively with TSH concentrations.

Endothelial expression of the receptor for advanced glycation end products in experimental diabetes / Expresión endotelial del receptor para productos finales de glicación avanzada en diabetes experimental

The receptor for advanced glycation end products (RAGE) is implicated in the pathogenesis of several chronic diseases including diabetes. The interaction between RAGE and advanced glycation end products (AGEs) promotes gene expression, enhances the release of proinflammatory molecules and causes the generation of oxidative stress in numerous cell types. The aim of this investigation was to evaluate the effect of enalapril and losartan on RAGE expression in abdominal aortic endothelium of rats with experimentally induced diabetes. Male Sprague-Dawley rats, weighing approximately 150 - 200 g, were used. Diabetes was induced in 30 rats by intravenous administration of a single dose of 55 mg/kg body weight of streptozotocin (ETZ). The following groups were studied: control (n=10), diabetic (n=10), losartan-treated diabetic (n=10) and enalapril-treated diabetic (n=10) rats. RAGE expression in aortic endothelium was determined by indirect immunofluorescence. A significant increase in RAGE expression was observed in diabetic animals versus controls (p<0.001), there was a decrease in RAGE expression, in animals treated with losartan versus controls (p<0.01) and in those treated with enalapril (p<0.05) versus control and versus diabetes + vehicle. In conclusion, in the experimental model of ETZ-induced diabetes, there is an increase in RAGE expression at the level of the abdominal aortic endothelium, which can be reversed by treatment with losartan and/or enalapril, two drugs that block the renin-angiotensin system, suggesting its involvement in the molecular events related to vascular damage during diabetes.

El receptor para productos finales de glicación avanzada (RAGE) está implicado en la patogénesis de varias enfermedades crónicas incluyendo la diabetes. La interacción entre RAGE y los productos finales de glicación avanzada (AGEs), promueve la expresión génica, potencia la liberación de moléculas proinflamatorias y provoca la generación de estrés oxidativo en numerosos tipos de células. El objetivo de esta investigación fue evaluar el efecto del enalapril y el losartán sobre la expresión de RAGE en el endotelio de la aorta abdominal de ratas con diabetes inducida experimentalmente. Se utilizaron ratas Sprague-Dawley machos, con un peso aproximado de entre 150 - 200 g. La diabetes se indujo en 30 ratas mediante la administración intravenosa de una sola dosis de 55 mg/Kg de peso corporal de estreptozotocina (ETZ). Se estudiaron los siguientes grupos: ratas control (n=10), diabéticas (n=10), diabéticas tratadas con losartán (n=10) y diabéticas tratadas con enalapril (n=10). La expresión de RAGE en el endotelio aórtico se determinó por inmunofluorescencia indirecta. Se observó un incremento significativo en la expresión de RAGE en los animales diabéticos versus los controles (p<0.001), hubo una disminución en la expresión de RAGE, en los animales tratados con losartán versus los controles (p<0.01) y en los tratados con enalapril (p<0.05) versus control y versus diabetes + vehículo. En conclusión, en el modelo experimental de diabetes inducida por ETZ, existe un incremento en la expresión de RAGE a nivel del endotelio de la aorta abdominal, la cual puede revertirse mediante el tratamiento con losartán y/o enalapril, dos fármacos bloqueadores del sistema renina-angiotensina, lo cual sugiere la participación del mismo en los acontecimientos moleculares relacionados con el daño vascular durante la diabetes.

Diabetes, heart damage, and angiotensin II. What is the relationship link between them? A minireview.

Cardiovascular complications are the main cause of mortality and morbidity in the diabetic patients, in whom changes in myocardial structure and function have been described. Numerous molecular mechanisms have been proposed that could contribute to the development of a cardiac damage. In this regard, angiotensin II (Ang II), a proinflammatory peptide that constitutes the main effector of the renin-angiotensin system (RAS) has taken a relevant role. The aim of this review was to analyze the role of Ang II in the different biochemical pathways that could be involved in the development of cardiovascular damage during diabetes. We performed an exhaustive review in the main databases, using the following terms: angiotensin II, cardiovascular damage, renin angiotensin system, inflammation, and diabetes mellitus. Classically, the RAS has been defined as a complex system of enzymes, receptors, and peptides that help control the blood pressure and the fluid homeostasis. However, in recent years, this concept has undergone substantial changes. Although this system has been known for decades, recent discoveries in cellular and molecular biology, as well as cardiovascular physiology, have introduced a better understanding of its function and relationship to the development of the diabetic cardiomyopathy.

Elevación del índice neutrófilo/linfocito y su relación con la proteína C reactiva en pacientes con diabetes mellitus tipo 2 / Elevation of the neutrophil/lymphocyte ratio and its relationship to C-reactive protein in patients with type 2 diabetes mellitus

Introducción: la proporción entre el recuento absoluto de neutrófilos y el recuento absoluto de linfocitos (índice de neutrófilos/linfocitos, INL) se ha convertido en los últimos años en un marcador crucial de inflamación sistémica, y se ha descrito que su elevación se relaciona con numerosas enfermedades inflamatorias crónicas. Objetivos: determinar el índice de neutrófilos/linfocitos (INL) en pacientes con diabetes mellitus tipo 2 (DM2), comparar con no diabéticos y establecer su correlación con la concentración de proteína C reactiva ultrasensible en una población de la localidad de Riobamba, Ecuador. Materiales y métodos: se realizó una investigación de tipo descriptiva, correlacional, de corte transversal, en el período comprendido desde julio de 2019 a febrero de 2020. Se seleccionaron 80 individuos para participar en el proyecto: 25 sujetos controles y 55 pacientes con diagnóstico de DM2. A cada sujeto se le extrajo una muestra de sangre en ayunas para la determinación de glucosa, colesterol total, triglicéridos, HDL colesterol, LDL colesterol, proteína C reactiva ultrasensible (PCR-us), hemoglobina glicosilada (HbA1c), recuento total de leucocitos, neutrófilos y linfocitos. Resultados: se encontró un incremento significativo en la concentración de glucosa (p<0,0001), HbA1c (p<0,0001), índice de masa corporal (IMC) (p<0,0001), PCR-us (p<0,0001), recuento absoluto de neutrófilos (p=0,001), recuento absoluto de linfocitos (p=0,04) e INL (p=0,0005), y una reducción significativa del HDL colesterol (p=0,02) en los pacientes con DM2 vs los controles. Se observó una correlación positiva (p<0,0001; r=0,7774) entre el INL y la PCR-us en los pacientes con DM2. Conclusiones: los pacientes con DM2 experimentaron elevación en el INL que se correlacionó con el incremento en la concentración de la PCR-us.

Introduction: the ratio between the absolute neutrophil count and the absolute lymphocyte count (neutrophil/lymphocyte ratio, NLR) has become a crucial marker of systemic inflammation in recent years, and its elevation has been described as being related to numerous chronic inflammatory diseases. Objectives: to determine the neutrophil/lymphocyte ratio (NLR) in patients with type 2 diabetes mellitus (T2DM), to compare with non-diabetics and to establish its correlation with the concentration of ultrasensitive C-reactive protein in a population of the town of Riobamba, Ecuador. Materials and methods: a descriptive, correlational, crosssectional, research was conducted from July 2019 to February 2020. Eighty individuals were selected to participate in the project, 25 control subjects and 55 patients with a diagnosis of T2DM. Each subject had a fasting blood sample drawn for the determination of glucose, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, ultrasensitive C-reactive protein (hs-CRP), glycosylated hemoglobin (HbA1c), total leukocyte count, neutrophils and lymphocytes. Results: a significant increase in glucose concentration (p<0.0001), HbA1c (p<0.0001), body mass index (BMI) (p<0.0001), hs-CRP (p<0.0001), absolute neutrophil count (p=0.001), absolute lymphocyte count (p=0.04), and NLR (p=0.0005), and a significant reduction in HDL cholesterol (p=0.02), were found in patients with T2DM vs controls. A positive correlation (p<0.0001; r=0.7774) was observed between NLR and hs-CRP in patients with T2DM. Conclusions: patients with T2DM experience elevation in NLR which correlates with increase in hs-CRP concentration.

C-reactive protein as an effector molecule in Covid-19 pathogenesis.

The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ systems. Damage induced by the virus is related to dysfunctional activity of the immune system, but the activity of molecules such as C-reactive protein (CRP) as a factor capable of inducing an inflammatory status that may be involved in the severe evolution of the disease, has not been extensively evaluated. A systematic review was performed using the NCBI-PubMed database to find articles related to Covid-19 immunity, inflammatory response, and CRP published from December 2019 to December 2020. High levels of CRP were found in patients with severe evolution of Covid-19 in which several organ systems were affected and in patients who died. CRP activates complement, induces the production of pro-inflammatory cytokines and induces apoptosis which, together with the inflammatory status during the disease, can lead to a severe outcome. Several drugs can decrease the level or block the effect of CRP and might be useful in the treatment of Covid-19. From this review it is reasonable to conclude that CRP is a factor that can contribute to severe evolution of Covid-19 and that the use of drugs able to lower CRP levels or block its activity should be evaluated in randomized controlled clinical trials.

La desventaja de los hombres frente a la Covid-19: análisis de la influencia del sexo sobre la respuesta inmunitaria ante la infección por SARS-Cov-2 / The disadvantage of men against COVID-19: analysis of the influence of sex on the immune response to SARS-CoV-2 infection

mundo se encuentra en medio de la pandemia de la enfermedad por coronavirus 2019 (COVID-19). En la mayoría de los países, la tasa de mortalidad, así como, la severidad de la enfermedad es más alta en hombres que en mujeres. Este sesgo sexual sugiere que los hombres son más propensos a desarrollar complicaciones graves o a sucumbir a las mismas, lo que conduce a la muerte. Por lo tanto, es importante comprender los elementos biológicos basados en el sexo que inciden en la respuesta inmunitaria. El objetivo de ésta revisión fue hacer un análisis en relación a la evidencia disponible sobre los diferentes factores que permitirían explicar esta disparidad sexual. Abordamos las diferencias en la respuesta inmunitaria en ambos sexos tomando en cuenta el aspecto genético, hormonal y el papel del sistema renina-angiotensina. Para ello, se realizó una búsqueda minuciosa en diferentes bases de datos utilizando las siguientes palabras clave: (Diferencia de sexo, genética, hormonas sexuales, COVID-19, SARS-CoV-2, respuesta inmunitaria, inflamación, hombres, mujeres). Los resultados de nuestro análisis ofrecen una comprensión más clara sobre la influencia de las diferencias sexuales en la capacidad de respuesta a una infección, con especial énfasis en la infección por SARS-CoV-2. Conocer estos factores no solo ayudará a comprender mejor la patogenia de la COVID-19, sino, además, guiará el diseño de terapias efectivas para la medicina personalizada basada en las diferencias sexuales

The world is during the 2019 coronavirus disease pandemic (COVID-19). In most countries, the mortality rate, as well as, the severity of the disease is higher in men than in women. This sex bias suggests that men are more likely to develop severe complications or succumb to severe complications, leading to death. Therefore, it is important to understand the sex-based biological elements that influence the immune response. The aim of this review was to review the available evidence on the different factors that could explain this sex disparity. We addressed the differences in the immune response in both sexes taking into account genetic, hormonal and the role of the renin-angiotensin system. For this purpose, a thorough search was performed in different databases using the following keywords: (Sex difference, genetics, sex hormones, COVID-19, SARS-CoV-2, immune response, inflammation, men, women). The results of our analysis provide a clearer understanding on the influence of sex differences on the ability to respond to an infection, with special emphasis to SARS-CoV-2 infection. Knowing these factors will not only help to better understand the pathogenesis of COVID-19, but will also guide the design of effective therapies for personalized medicine based on sex differences.

SARS-CoV-2 infection represents a high risk for the elderly: analysis of pathogenesis.

As people get older, age-related alterations occur that lead to increased susceptibility to disease. In the current COVID-19 pandemic, older people are particularly susceptible to a SARS-CoV-2 infection developing into severe disease. The objective of this review was to examine the literature regarding factors that may explain the tendency of this population to develop severe COVID-19. Research articles considered in this review were searched for in EMBASE, PubMed, and Web of Science from December 2019 to December 2020. Citations were screened by two independent reviewers. Studies of the immune system in older individuals found alterations in both the adaptive and innate immune systems. The adaptive system is depressed in its functions, and the innate system is in a pro-inflammatory state that can lead to chronic disease. This pro-inflammatory state may be related to a severe course of disease in COVID-19. This review shows that the level of evidence supporting an association between immune alterations in the elderly and susceptibly to severe progression of SARS-CoV-2 infection is generally consistent. Preventive measures such as early antiviral treatment are of key importance for prevention of severe progression of COVID19.

Nanoantibodies: small molecules, big possibilities.

Camelids (camels, dromedaries, alpacas, llamas, and vicuñas) contain in their serum conventional heterodimeric antibodies as well as antibodies with no light chains (L) in their structure and composed of only heavy chains (H), called as HcAbs (heavy chain antibodies). Variable fragments derived from these antibodies, called as VHH or nanoantibodies (Nbs), have also been described. Since their discovery, Nbs have been widely used in the fields of research, diagnostics, and pharmacotherapy. Despite being approximately one-tenth the size of a conventional antibody, they retain similar specificity and affinity to conventional antibodies and are much easier to clone and manipulate. Their unique properties such as small size, high stability, strong antigen binding affinity, water solubility, and natural origin make them suitable for the development of biopharmaceuticals and nanoreagents. The present review aims to describe the main structural and biochemical characteristics of these antibodies and to provide an update on their applications in research, biotechnology, and medicine. For this purpose, an exhaustive search of the biomedical literature was performed in the following databases: Medline (PubMed), Google Scholar, and ScienceDirect. Meta-analyses, observational studies, review articles, and clinical guidelines were reviewed. Only original articles were considered to assess the quality of the evidence.

Acute post-streptococcal glomerulonephritis: analysis of the pathogenesis.

Increasing evidence supports a central role of the immune system in acute post streptococcal glomerulonephritis (APSGN), but the current view of how streptococcal biology affects immunity, and vice versa, remains to be clarified. Renal glomerular immune complex deposition is critical in the initiation of APSGN; however, mechanisms previous to immune complex formation could modulate the initiation and the progression of the disease. Initial and late renal events involved in the nephritis can also be related to host factors and streptococcal factors. In this review we describe the mechanisms reported for the APSGN pathogenesis, the interactions of streptococcal products with renal cells and leukocytes, the possible effects of different nephritogenic antigens in the renal environment and the possibility that APSGN is not just due to a single streptococcal antigen and its antibody; instead, kidney damage may be the result of different factors acting at the same time related to both streptococcus and host factors. Addressing these points should help us to better understand APSGN physiopathology.

Angiotensin II Induces Increased Myocardial Expression of Receptor for Advanced Glycation End Products, Monocyte/Macrophage Infiltration and Circulating Endothelin-1 in Rats With Experimental Diabetes.

OBJECTIVES: It is known that the receptor for advanced glycation end products (RAGE) activation is involved in the pathogenesis of cardiovascular disease in diabetes. Previous studies have shown the presence of angiotensin II (Ang II) in diabetes, suggesting a role for this hormone during the disease. However, the association between RAGE and Ang II during pathologic cardiac remodelling after streptozotocin (STZ)-induced diabetes remains unclear. Because Ang II is capable of inducing pro-inflammatory events, blocking its production (enalapril), and its action on its receptor (losartan) could decrease inflammatory events in the myocardium in this experimental model of diabetes. Thus, the aim of this study was to assess the association between RAGE expression, inflammatory events and Ang II in the myocardium during STZ-induced diabetes. METHODS: Diabetes was induced by intravenous injection of STZ in Sprague-Dawley rats. Myocardial expressions of RAGE, monocyte/macrophage (ED-1-positive cells) infiltration and the intercellular adhesion molecule-1 were determined by histochemical methods. Levels of circulating endothelin-1 (ET-1) were determined by enzyme-linked immunoassay. Effects of Ang II included blocking using losartan (15 mg/kg body weight per day by gastric gavage) or enalapril (18 mg/kg body weight per day by gastric gavage). RESULTS: Increased expression of both RAGE and ED-1 was seen in the myocardium, but expression of myocardial vascular intercellular adhesion molecule-1 remained unchanged. Circulating levels of ET-1 in STZ rats were increased. Renin‒angiotensin system inhibition decreased expression of myocardial RAGE, ED-1 and ET-1. CONCLUSIONS: The present findings suggest a role for Ang II in myocardial inflammation in STZ-induced diabetes mediated by RAGE and ET-1.

Renal oxidative stress and renal CD8(+) T-cell infiltration in mercuric chloride-induced nephropathy in rats: role of angiotensin II.

Mercuric chloride (HgCl2) induces kidney damage, in part, through oxidative stress. A role for angiotensin II (Ang II) in pro-inflammatory events in a model of acute HgCl2-induced nephropathy was reported. Ang II is a potent oxidative stress inducer; however, its role in oxidative/anti-oxidative events in HgCl2-induced nephropathy remains unknown. The aim of this study was to determine the role of Ang II in the oxidative stress and renal infiltration of CD8(+) T-cells after an acute HgCl2 intoxication. Three groups of Sprague Dawley rats were treated with a single subcutaneous dose of 2.5 mg/kg HgCl2: for 3 days prior to and for 4 days after that injection, rats in one group received Losartan (30 mg/kg), in another group Enalapril (30 mg/kg) or normal saline in the last group. Two other groups of drug-treated rats received saline in place of HgCl2. A final group of rats received saline in place of HgCl2 and the test drugs. All treatments were via gastric gavage. At 96 h after the vehicle/HgCl2 injection, blood and kidney samples were harvested. Renal sections were homogenized for measures of malondialdehyde (MDA), reduced glutathione (GSH) and catalase activity. Frozen sections were studied for the presence of superoxide anion ([Formula: see text]) and CD8(+) T-cells. HgCl2-treated rats had increased interstitial and tubular expression of [Formula: see text], high levels of MDA, normal catalase activity and GSH content, increased levels of interstitial CD8(+) T-cells and an increased percentage of necrotic tubules. Anti-Ang II treatments diminished the HgCl2-induced increases in interstitial [Formula: see text], CD8(+) T-cells and tubular damage and increased catalase and GSH expression above that due to HgCl2 alone; the HgCl2-induced high MDA levels were unaffected by the drugs. These data provide new information regarding the potential role of Ang II in the oxidative stress and renal CD8(+) T-cell infiltration that occur during HgCl2 nephropathy.

Increased C-reactive protein and decreased Interleukin-2 content in serum from obese individuals with or without insulin resistance: Associations with leukocyte count and insulin and adiponectin content.

AIMS: Chronic inflammation in obesity is associated with co-morbidities such as, hyperglycemia, hypertension and hyperlipidemia. Leukocytes play an important role in this inflammation and C-reactive protein (CRP) and Interleukin-2 (IL-2) can be important effectors during the immune response in obesity; however, the initial inflammatory events in obesity remain unclear. The aim of this study was to determine the circulating levels of CRP, IL-2, insulin and adiponectin, their association and the association with leukocyte count in obese individuals without co-morbidities and with or without insulin resistance (IR). MATERIALS AND METHODS: Nineteen obese non-diabetic and 9 lean subjects were studied for serum levels of CRP, IL-2, insulin, adiponectin, lipids, glycated hemoglobin, glycemia, for homeostasis model assessment of insulin resistance (HOMA-IR), arterial pressure and anthropometric parameters, and for leukocyte counts. Neutrophil/lymphocyte ratio (N/L) was calculated using the loge of leukocyte counts. Associations were determined by Pearson's correlation. RESULTS: None of the studied groups presented co-morbidities and two groups of obese individuals with normal or high levels of insulin (IR) were found. Increased CRP concentration and decreased IL-2 and adiponectin concentrations in obese were observed. Positive correlation between leukocyte type counts with CRP in obese with IR was found; however, no correlations with IL-2 in obese were observed. Insulin in obese were positively correlated with CRP and negatively correlated with IL-2 in IR obese individuals. Adiponectin in obese was negatively correlated with CRP. CONCLUSION: CRP and IL-2 may represent two important effectors in the early inflammatory events in obese individuals without co-morbidities. Adiponectin and insulin may be involved in anti-inflammatory events.

Increased proinflammatory markers and lipoperoxidation in obese individuals: Inicial inflammatory events?

BACKGROUND: Chronic inflammation associated to obesity increases the risk for developing insulin resistance (IR), hyperglycemia, hypertension and hyperlipidemia. The initial factors involved in generating the inflammatory events in the obesity remain unclear. Therefore, this study was aimed to determine inflammatory and oxidative markers in the blood of obese individuals with normal clinical and biochemical parameters and with or without IR. METHODS: Nineteen obese non-diabetic and nine lean subjects were studied for serum levels of TNF-α, IL-1ß, adiponectin, angiotensin II, insulin, malondialdehyde (MDA) and the expressions of RAGE (advanced glycation end product receptor), AT1 (Ang II receptor), s100A12 protein (RAGE ligand) and nuclear factor-κB (NF-κB) in circulating mononuclear cells (CMC) by available antibodies and commercial kits. CMC were also cultured to determine pro-inflammatory mediators. RESULTS: Insulin was increased in obese subjects with IR. Decreased serum adiponectin in obese individuals and increased TNF-α, IL-1ß and CMC bearing RAGE, AT1 and s100A12 in obese individuals without IR were found. High values of serum MDA in obese subjects were observed. Similar TNF-content in cultures from obese and controls, increased cellular IL-1ß content in cultures from obese individuals without IR and high content of MDA in supernatants from obese individual cultures were observed. CONCLUSIONS: The inflammatory events were mainly observed in obese individuals without IR. The absent of inflammatory events and high levels of insulin in obese subjects with IR, suggest a protector role of insulin for developing inflammatory events. These data can represent initial aspects of the chronic inflammation observed in the obesity.

Association of obesity with leukocyte count in obese individuals without metabolic syndrome.

AIMS: Inflammation in obesity is associated to insulin resistance (IR), hyperglycemia, hypertension and hyperlipidemia. Leukocytes play an important role in obesity associated inflammation. The initial factors that generate the inflammatory events in the obesity remain unclear. Therefore, the aim of this study was to determine the association of circulating leukocytes with clinical and biochemical parameters in obese individuals with clinical and biochemical parameters in normal range and with or without IR. METHODS: Nineteen obese non-diabetic and 9 lean subjects were studied for serum levels of insulin, lipids, glycated hemoglobin, glycemia, for clinical parameters as HOMA-IR, arterial pressure and anthropometric parameters, and for leukocyte counts. Neutrophil/lymphocyte ratio (N/L) was calculated using the loge of leukocyte counts. Association between leukocytes and studied parameters was determined by Pearson's correlation. RESULTS: Two groups of obese individuals were observed: with high levels of insulin (with IR) and with normal levels (without IR). Positive correlations were observed between leukocyte and lymphocyte counts with body mass index and HOMA-IR and negative correlation with decreased HDL levels. Lymphocytes correlated with increased levels of insulin. Leukocytes and neutrophils correlated positively with increased visceral fat and liver steatosis. These associations were absent in the obese group without IR. N/L ratio did not show correlations with studied parameters. The leukocyte associations were mainly observed in obese individuals with IR. CONCLUSIONS: These data may represent initial leukocyte associations with morbidity features and define two different obese individuals that may evolve to the chronic inflammation observed in the obesity.