ABSTRACT
This work describes a mathematical model for handwriting devices without a specific reference surface (SRS). The research was carried out on two hypotheses: the first considers possible circular segments that could be made during execution for the reconstruction of the trace, and the second is the combination of lines and circles. The proposed system has no flat reference surface, since the sensor is inside the pencil that describes the trace, not on the surface as in tablets or cell phones. An inertial sensor was used for the measurements, in this case, a commercial Micro-Electro Mechanical sensor of linear acceleration. The tracking device is an IMU sensor and a processing card that allows inertial measurements of the pen during on-the-fly tracing. It is essential to highlight that the system has a non-inertial reference frame. Comparing the two proposed models shows that it is possible to construct shapes from curved lines and that the patterns obtained are similar to what is recognized; this method provides an alternative to quaternion calculus for poorly specified orientation problems.
ABSTRACT
Chronic kidney disease (CKD) is a progressive disease with a high mortality rate and a worldwide prevalence of 13.4%, triggered by various diseases with high incidence. The aim of the present study was to investigate the anti-inflammatory and antifibrotic effect of pioglitazone on kidney in an adenine-induced Wistar rats and the mechanisms possibly involved. CKD was induced in 40 rats. Rats were divided into two groups, which were split into the following sub-groups: i) Therapeutic (pioglitazone administered after renal damage) divided into intact (healthy), adenine (CKD) and adenine/pioglitazone (treatment) and ii) prophylactic (adenine and pioglitazone administered at the same time) split into intact (healthy), adenine (CKD), endogenous reversion (recovery without treatment), adenine/pioglitazone (treatment) and pioglitazone sub-groups. Reverse transcription-quantitative PCR (collagen I, α-SMA and TGF-ß), and hematoxylin-eosin, Masson's trichrome and Sirius red staining were performed to measure histological markers of kidney damage, also the serum markers (urea, creatinine and uric acid) were performed, for analyze the effects of pioglitazone. In the adenine/pioglitazone rats of the therapeutic group, renal function parameters such as eGFR increased and serum creatinine decreased from those of untreated rats (CKD), however the renal index, serum urea, abnormalities in renal morphology, inflammatory cells and relative gene expression of collagen I, α-SMA and TGF-ß did not change relative to the CKD rats. In adenine/pioglitazone rats, extracellular matrix collagen accumulation was significantly lower than the CKD rats. On the other hand, in adenine/pioglitazone rats of the prophylactic group, the renal index, creatinine, urea, uric acid serum and relative gene expression of collagen I, α-SMA, and TGF-ß were significantly lower, as well as the presence of 2,8-dihydroxyadenine crystals, and extracellular matrix collagen compared with CKD rats. In addition, the eGFR in the treatment group was similar to healthy rats, renal morphology was restored, and inflammatory cells were significantly lower. In conclusion, pioglitazone has a nephroprotective effect when administered in the early stages of kidney damage, reducing inflammatory and fibrotic processes and improving glomerular filtration rate. Furthermore, in the late phase of treatment, a tendency to decrease creatinine and increase eGFR was observed.
ABSTRACT
Chronic kidney disease (CKD) is characterized by renal parenchymal damage leading to a reduction in the glomerular filtration rate. The inflammatory response plays a pivotal role in the tissue damage contributing to renal failure. Current therapeutic options encompass dietary control, mineral salt regulation, and management of blood pressure, blood glucose, and fatty acid levels. However, they do not effectively halt the progression of renal damage. This review critically examines novel therapeutic avenues aimed at ameliorating inflammation, mitigating extracellular matrix accumulation, and fostering renal tissue regeneration in the context of CKD. Understanding the mechanisms sustaining a proinflammatory and profibrotic state may offer the potential for targeted pharmacological interventions. This, in turn, could pave the way for combination therapies capable of reversing renal damage in CKD. The non-replacement phase of CKD currently faces a dearth of efficacious therapeutic options. Future directions encompass exploring vaptans as diuretics to inhibit water absorption, investigating antifibrotic agents, antioxidants, and exploring regenerative treatment modalities, such as stem cell therapy and novel probiotics. Moreover, this review identifies pharmaceutical agents capable of mitigating renal parenchymal damage attributed to CKD, targeting molecular-level signaling pathways (TGF-ß, Smad, and Nrf2) that predominate in the inflammatory processes of renal fibrogenic cells.
ABSTRACT
Entamoeba histolytica (E. histolytica) is a protozoan responsible for intestinal amebiasis in at least 500 million people per year, although only 10% of those infected show severe symptoms. It is known that E. histolytica captures molecules released during the host immune response through membrane receptors that favor its pathogenetic mechanisms for the establishment of amebic invasion. It has been suggested that E. histolytica interacts with acetylcholine (ACh) through its membrane. This promotes the increase of virulence factors and diverse mechanisms carried out by the amoeba to produce damage. The aim of this study is to identify a membrane receptor in E. histolytica trophozoites for ACh. Methods included identification by colocalization for the ACh and Gal/GalNAc lectin binding site by immunofluorescence, western blot, bioinformatic analysis, and quantification of the relative expression of Ras 5 and Rab 7 GTPases by RT-qPCR. Results show that the Gal/GalNAc lectin acts as a possible binding site for ACh and this binding may occur through the 150 kDa intermediate subunit. At the same time, this interaction activates the GTPases, Ras, and Rab, which are involved in the proliferation, and reorganization of the amoebic cytoskeleton and vesicular trafficking. In conclusion, ACh is captured by the parasite, and the interaction promotes the activation of signaling pathways involved in pathogenicity mechanisms, contributing to disease and the establishment of invasive amebiasis.
Subject(s)
Amebiasis , Dysentery, Amebic , Entamoeba histolytica , Humans , Entamoeba histolytica/metabolism , Lectins/metabolism , Receptors, Cholinergic/metabolism , Protozoan Proteins/metabolism , Dysentery, Amebic/parasitologyABSTRACT
Acanthamoeba griffini is known to cause amoebic keratitis (AK); its main causes are inadequate hygiene when contact lenses are handled and/or its prolonged use at night, as well as the use of contact lenses during underwater activities. The most used treatment for AK is the combination of propamidine isethionate combined with polyhexamethylene biguanide, which disrupts the cytoplasmic membrane, and damages cellular components and respiratory enzymes. We proposed an immunoconjugate treatment obtained from Acanthamoeba immunized rabbit serum combined with propamidine isethionate; the corneas of hamsters inoculated with A. griffini (MYP2004) were treated with the combined, at 1, 2, and 3 weeks. Propamidine isethionate is frequently used for AK treatment, in vivo study we are found IL-1ß and IL-10 expression and caspase 3 activity is significantly increased with respect to the group that was inoculated with the amoeba without receiving any treatment, suggesting that it may be an effect of the toxicity of this drug on the corneal tissue. Application of the immunoconjugate showed enhanced amoebicidal and anti-inflammatory activities, with comparison to propamidine isethionate only. The aim of this study is to evaluate the effect of the immunoconjugate of propamidine isethionate and polyclonal antibodies as a treatment of AK in golden hamsters (Mesocricetus auratus).
ABSTRACT
Arginine vasopressin (AVP) is a naturally occurring hormone synthesized in the hypothalamus. AVP demonstrates pro-fibrotic effects as it stimulates hepatic stellate cells to secrete transforming growth factor-ß (TGF-ß) and collagen. Previous work in liver cirrhotic (CCL4 -induced) hamsters demonstrated that AVP deficiency induced by neurointermediate pituitary lobectomy (NIL) can restore liver function. Therefore, we hypothesized that liver fibrosis would decrease in portocaval anastomosis (PCA) rats, which model chronic liver diseases, when they are treated with the V1a-V2 AVP receptor antagonist conivaptan (CV). In this study, changes in liver histology and gene expression were analysed in five experimental groups: control, PCA, NIL, PCA + NIL and PCA + CV, with NIL surgery or CV treatment administered 8 weeks after PCA surgery. Body weight gain was assessed on a weekly basis, and serum liver function, liver weight and liver glycogen content were assessed following euthanasia. Most PCA-induced phenotypes were reverted to normal levels following AVP-modelled deficiency, though hypoglycemia and ammonium levels remained elevated in the PCA + CV group. Liver histopathological findings showed a significant reversal in collagen content, less fibrosis in the triad and liver septa and increased regenerative nodules. Molecular analyses showed that the expression of fibrogenic genes (TGF-ß and collagen type I) decreased in the PCA + CV group. Our findings strongly suggest that chronic NIL or CV treatment can induce a favourable microenvironment to decrease liver fibrosis and support CV as an alternative treatment for liver fibrosis.
Subject(s)
Diabetes Insipidus, Neurogenic , Receptors, Vasopressin , Cricetinae , Rats , Animals , Receptors, Vasopressin/genetics , Antidiuretic Hormone Receptor Antagonists/pharmacology , Arginine Vasopressin/pharmacology , Liver Cirrhosis/drug therapy , Anastomosis, Surgical , ArginineABSTRACT
Secretions of beneficial intestinal bacteria can inhibit the growth and biofilm formation of a wide range of microorganisms. Curcumin has shown broad spectrum antioxidant, anti-inflammatory, and antimicrobial potential. It is important to evaluate the influence of these secretions with bioactive peptides, in combination with curcumin, to limit growth and inhibit biofilm formation of pathogenic bacteria of importance in aquaculture. In the present study, the supernatants of Lactoccocus lactis NZ9000, Lactobacillus rhamnosus GG and Pediococcus pentosaceus NCDO 990, and curcumin (0,1,10,25 and 50 µM) were used to evaluate their efficacy in growth, inhibition biofilm and membrane permeability of Aeromonas hydrophila CAIM 347 (A. hydrophila). The supernatants of probiotics and curcumin 1,10 and 25 µM exerted similar effects in reducing the growth of A. hydrophila at 12 h of interaction. The supernatants of the probiotics and curcumin 25 and 50 µM exerted similar effects in reducing the biofilm of A. hydrophila. There is a significant increase in the membrane permeability of A. hydrophila in interaction with 50 µM curcumin at two hours of incubation and with the supernatants separately in the same period. Different modes of action of curcumin and bacteriocins separately were demonstrated as effective substitutes for antibiotics in containing A. hydrophila and avoiding the application of antibiotics. The techniques implemented in this study provide evidence that there is no synergy between treatments at the selected concentrations and times.
Subject(s)
Curcumin , Lacticaseibacillus rhamnosus , Lactococcus lactis , Aeromonas hydrophila , Animals , Anti-Bacterial Agents/pharmacology , Curcumin/pharmacology , Pediococcus pentosaceusABSTRACT
OBJECTIVES: Fibromyalgia (FM) is a disease treated with various therapeutic approaches that have limited success. Pulsed electromagnetic field therapy has been proposed as a possible solution to reduce several symptoms. This study aims to analyse the therapeutic effects of transcranial low-intensity magnetic stimulation (LIMS) in women diagnosed with FM at 2, 12 and 24 weeks from the last LIMS administration treatment session. METHODS: 560 women (53.7 ± 11.3 years) diagnosed with FM according to the ACR 2016 criteria were randomly allocated in two groups: 280 received standard pharmacological treatment and 280 received the same treatment plus eight sessions of LIMS, 20 minutes long, once a week. The variables analysed were the widespread pain index (WPI), symptoms severity score (SS score) and the Spanish-validated version of the FM impact questionnaire (S-FIQ). The evaluations were performed at the beginning of LIMS treatment and at 2, 12 and 24 weeks after the end of the last LIMS treatment session. RESULTS: From the second week after the last LIMS session, there was significant improvement (p <0.001) in the variables WPI, SS score and S-FIQ. This improvement was maintained throughout the 24 weeks of monitoring after the last intervention. The age of the patients and the severity of the symptoms at the time of diagnosis did not affect the improvement observed in the three variables studied. CONCLUSIONS: Treatment with LIMS for eight weeks resulted in significant improvement in FM diagnostic variables, which was maintained up to 24 weeks after the last treatment session. This therapy could be recommended as a part of a multimodal approach for FM treatment.
Subject(s)
Fibromyalgia , Female , Fibromyalgia/diagnosis , Fibromyalgia/therapy , Humans , Pain , Pain Measurement/methods , Quality of Life , Severity of Illness Index , Surveys and Questionnaires , Transcranial Magnetic StimulationABSTRACT
BACKGROUND: During pregnancy metabolic disorders that affect differently the fetus, are known. These could be early or late disorders. OBJECTIVES: To analyze different biochemical parameters in umbilical cord blood (UCB) of healthy and pathological newborns from mothers with metabolic disorders. MATERIALS AND METHODS: Samples from UCB (121) were analyzed of newborn from mothers with metabolic disorders who attended at Obstetrics Division. Patients were consecutive, prospective and transversally studied. Newborn were classified as healthy (n = 65) and pathological (n = 56). The maternal metabolic disorders were gestational or non-gestational diabetes, glucose intolerance, insulin resistance and/or obesity).The disorders of the pathological newborns were intrauterine growth restriction (IUGR) and/or fetal distress. Glucose (Glu), urea, creatinine, uric acid (UA), total bilirubin (TB), total proteins (TP), albumin (Alb), transaminases (ALT/AST), alkaline-phosphatase (ALP), gammaglutamyltranspeptidase (GGT), creatinkinasa (CK), lactatedehydrogenase, amylase (amy), pseudocholinesterase, iron, calcium, phosphorus, magnesium (Mg), sodium, potassium, chlorine, cholesterol (Chol), HDL-Chol, LDL-Chol, triglycerides (TG), high sensitivity C reactive protein (hsCRP) were determined by recommended methods. T-Student's and Mann Withney tests were applied, p < .05. RESULTS: Pathological neonates (n: 56) showed a significant decrease in maternal gestation weeks (GW) and in newborn weight (NW) with respect to healthy newborns (n: 65) from mothers with metabolic disorders (p < .0001). Pathological neonates from mothers with metabolic pathologies (n: 56) showed significant increases in Chol, TG, TB (p < .01), LDL-Chol, UA, Mg, hsCRP, ALP levels (p < .05) and significant decreases in TP, Alb (p < .0001) and Glu, ALT, CK, GGT, amy (p < .05) in UCB with respect to healthy newborns. CONCLUSIONS: In pathological newborn, the decrease in GW and NW would be related to IUGR that accompany these metabolic disorders. The increases observed of the analyzed parameters would be related to cellular destruction associated to maternal pathology and decreases of the parameters to IUGR with hepatic immaturity.
Subject(s)
Metabolic Diseases , Pregnancy Complications , Pregnancy , Female , Infant, Newborn , Humans , Fetal Blood/metabolism , C-Reactive Protein/metabolism , Prospective Studies , Triglycerides , Cholesterol, LDL , Fetal Growth Retardation , Cholesterol , Uric Acid , gamma-Glutamyltransferase , Pregnancy Complications/metabolismABSTRACT
Liver diseases, including cirrhosis, viral hepatitis, and hepatocellular carcinoma, account for approximately two million annual deaths worldwide. They place a huge burden on the global healthcare systems, compelling researchers to find effective treatment for liver fibrosis-cirrhosis. Portacaval anastomosis (PCA) is a model of liver damage and fibrosis. Arginine vasopressin (AVP) has been implicated as a proinflammatory-profibrotic hormone. In rats, neurointermediate pituitary lobectomy (NIL) induces a permanent drop (80%) in AVP serum levels. We hypothesized that AVP deficiency (NIL-induced) may decrease liver damage and fibrosis in a rat PCA model. Male Wistar rats were divided into intact control (IC), NIL, PCA, and PCA+NIL groups. Liver function tests, liver gene relative expressions (IL-1, IL-10, TGF-ß, COLL-I, MMP-9, and MMP-13), and histopathological assessments were performed. In comparison with those in the IC and PCA groups, bilirubin, protein serum, and liver glycogen levels were restored in the PCA+NIL group. NIL in the PCA animals also decreased the gene expression levels of IL-1 and COLL-I, while increasing those of IL-10, TGF-ß, and MMP-13. Histopathology of this group also showed significantly decreased signs of liver damage with lower extent of collagen deposition and fibrosis. Low AVP serum levels were not enough to fully activate the AVP receptors resulting in the decreased activation of cell signaling pathways associated with proinflammatory-profibrotic responses, while activating cell molecular signaling pathways associated with an anti-inflammatory-fibrotic state. Thus, partial reversion of liver damage and fibrosis was observed. The study supports the crucial role of AVP in the inflammatory-fibrotic processes and maintenance of immune competence. The success of the AVP deficiency strategy suggests that blocking AVP receptors may be therapeutically useful to treat inflammatory-fibrotic liver diseases.
Subject(s)
Arginine Vasopressin/deficiency , Liver Cirrhosis/pathology , Liver Failure/immunology , Pituitary Gland/metabolism , Receptors, Vasopressin/metabolism , Animals , Arginine Vasopressin/blood , Disease Models, Animal , Humans , Hypophysectomy , Liver Cirrhosis/blood , Liver Cirrhosis/immunology , Liver Failure/blood , Liver Failure/pathology , Male , Pituitary Gland/surgery , Portacaval Shunt, Surgical , Rats , Rats, Wistar , Signal Transduction/immunologyABSTRACT
AIM: The objective of this work was to analyze the structural changes of the pancreatic islets in rats, after 6 month consuming regular and light cola for 6 months. Also, we have analyzed the possible role of PDX-1 in that process. Finally, with the available knowledge, we propose a general working hypothesis that explains the succession of phenomena observed. Previously, we reported evidence showing that chronic cola consumption in rats impairs pancreatic metabolism of insulin and glucagon and produces some alterations typically observed in the metabolic syndrome, with an increase in oxidative stress. Of note It is worth mentioning that no apoptosis nor proliferation of islet cells could be demonstrated. In the present study, 36 male Wistar rats were divided into three groups to and given free access to freely drink regular cola (C), light cola (L), or water (W, control). We assessed the impact of the three different beverages in on glucose tolerance, lipid levels, creatinine levels and immunohistochemical changes addressed for the expression of insulin, glucagon, PDX-1 and NGN3 in islet cells, to evaluate the possible participation of PDX-1 in the changes observed in α and ß cells after 6 months of treatment. Moreover, we assessed by stereological methods, the mean volume of islets (Vi) and three important variables: the fractional ß -cell area, the cross-sectional area of alpha (A α-cell) and beta cells (A ß-cell), and the number of ß and α cell per body weight. Data were analyzed by two-way ANOVA followed by Bonferroni's multiple t-test or by Kruskal-Wallis test, then followed by Dunn's test (depending on distribution). Statistical significance was set at p<0.05. Cola drinking caused impaired glucose tolerance as well as fasting hyperglycemia (mean:148; CI:137-153; p<0.05 vs W) and an increase of in insulin immunolabeling (27.3±19.7; p<0.05 vs W and L). Immunohistochemical expression for PDX-1 was significantly high in C group compared to W (0.79±0.71; p<0.05). In this case, we observed cytoplasmatic and nuclear localization. Likewise, a mild but significant decrease of in Vi was detected after 6 months in C compared to W group (8.2±2.5; p<0.05). Also, we observed a significant decrease of in the fractional ß cell area (78.2±30.9; p<0.05) compared to W. Accordingly, a reduced mean value of islet α and ß cell number per body weight (0.05±0.02 and 0.08±0.04 respectively; both p<0.05) compared to W was detected. Interestingly, consumption of light cola increased the Vi (10.7±3.6; p<0.05) compared to W. In line with this, a decreased cross-sectional area of ß-cells was observed after chronic consumption of both, regular (78.2±30.9; p<0.05) and light cola (110.5±24.3; p<0.05), compared to W. As for, NGN3, it was negative in all three groups. Our results support the idea that PDX-1 plays a key role in the dynamics of the pancreatic islets after chronic consumption of sweetened beverages. In this experimental model, the loss of islets cells might be attributed to autophagy, favored by the local metabolic conditions and oxidative stress.
Subject(s)
Carbonated Beverages/adverse effects , Islets of Langerhans/cytology , Islets of Langerhans/drug effects , Animals , Male , Rats , Rats, WistarABSTRACT
Entamoeba histolytica is an intestinal parasite that causes dysentery and amebic liver abscess. E. histolytica has the capability to invade host tissue by union of virulence factor Gal/GalNAc lectin; this molecule induces an adherence-inhibitory antibody response as well as to protect against amebic liver abscess (ALA). The present work showed the effect of the immunization with PEΔIII-LC3-KDEL3 recombinant protein. In vitro, this candidate vaccine inhibited adherence of E. histolytica trophozoites to HepG2 cell monolayer, avoiding the cytolysis, and in a hamster model, we observed a vaccine-induced protection against the damage to tissue liver and the inhibition of uncontrolled inflammation. PEΔIII-LC3-KDEL3 reduced the expression of TNF-α, IL-1ß, and NF-κB in all immunized groups at 4- and 7-day postinfection. The levels of IL-10, FOXP3, and IFN-γ were elevated at 7 days. The immunohistochemistry assay confirmed this result, revealing an elevated quantity of +IFN-γ cells in the liver tissue. ALA formation in hamsters immunized was minimal, and few trophozoites were identified. Hence, immunization with PEΔIII-LC3-KDEL3 herein prevented invasive amebiasis, avoided an acute proinflammatory response, and activated a protective response within a short time. Finally, this recombinant protein induced an increase of serum IgG.
Subject(s)
Entamoeba histolytica/immunology , Liver Abscess, Amebic/prevention & control , Protozoan Proteins/administration & dosage , Protozoan Vaccines/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Animals , Antibodies, Protozoan/blood , Disease Models, Animal , Entamoeba histolytica/genetics , Humans , Immunogenicity, Vaccine , Lectins/genetics , Lectins/immunology , Liver/immunology , Liver/parasitology , Liver/pathology , Liver Abscess, Amebic/blood , Liver Abscess, Amebic/parasitology , Liver Abscess, Amebic/pathology , Male , Mesocricetus , Protozoan Proteins/genetics , Protozoan Proteins/immunology , Protozoan Vaccines/genetics , Protozoan Vaccines/immunology , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunologyABSTRACT
BACKGROUND: The parasite Entamoeba histolytica is the causal agent of amoebiasis, a worldwide emerging disease. Amebic brain abscess is a form of invasive amebiasis that is both rare and frequently lethal. This condition always begins with the infection of the colon by E. histolytica trophozoites, which subsequently travel through the bloodstream to extraintestinal tissues. CASE PRESENTATION: We report a case of a 71-year-old female who reported an altered state of consciousness, disorientation, sleepiness and memory loss. She had no history of hepatic or intestinal amoebiasis. A preliminary diagnosis of colloidal vesicular phase neurocysticercosis was made based on nuclear magnetic resonance imaging (NMRI). A postsurgery immunofluorescence study was positive for the 140 kDa fibronectin receptor of E. histolytica, although a serum analysis by ELISA was negative for IgG antibodies against this parasite. A specific E. histolytica 128 bp rRNA gene was identified by PCR in biopsy tissue. The final diagnosis was cerebral amoebiasis. The patient underwent neurosurgery to eliminate amoebic abscesses and was then given a regimen of metronidazole, ceftriaxone and dexamethasone for 4 weeks after the neurosurgery. However, a rapid decline in her condition led to death. CONCLUSIONS: The present case of an individual with a rare form of cerebral amoebiasis highlights the importance of performing immunofluorescence, NMRI and PCR if a patient has brain abscess and a poorly defined diagnosis. Moreover, the administration of corticosteroids to such patients can often lead to a rapid decline in their condition.
Subject(s)
Brain Abscess/diagnosis , Brain Abscess/parasitology , Central Nervous System Parasitic Infections/diagnosis , Entamoebiasis/diagnosis , Aged , Animals , Brain Abscess/drug therapy , Brain Abscess/surgery , Ceftriaxone/administration & dosage , Central Nervous System Parasitic Infections/drug therapy , Central Nervous System Parasitic Infections/pathology , Central Nervous System Parasitic Infections/surgery , Combined Modality Therapy , DNA, Protozoan/analysis , Dexamethasone/administration & dosage , Drug Therapy, Combination , Entamoeba histolytica/genetics , Entamoeba histolytica/immunology , Entamoeba histolytica/isolation & purification , Entamoebiasis/drug therapy , Entamoebiasis/pathology , Entamoebiasis/surgery , Fatal Outcome , Female , Humans , Metronidazole/administration & dosage , Neurosurgical Procedures , Serologic TestsABSTRACT
Alrededor del 80 % de los casos sintomáticos de COVID-19 tienen una enfermedad leve a moderada, que no suele progresar a fases más avanzadas. El 14 % de los casos pueden progresar en unos 7 a 10 días a un cuadro severo pulmonar, mientras que un 6 % siguen deteriorándose en el tiempo ante una respuesta hiperinflamatoria o de tormenta de citoquinas, que conlleva a shock y falla de múltiples órganos. En general tienen mayor riesgo de progresión los individuos con factores de riesgo como edad mayor de 60 años, género masculino, obesidad, diabetes, hipertensión, inmunosupresión, trasplante de órganos sólidos, enfermedad renal, tabaquismo; pero eso no descarta la posibilidad aislada que individuos aparentemente sanos puedan presentar una evolución severa o diversas complicaciones pulmonares, renales, cardiovasculares, neurológicas, endocrinológicas, entre otras. Este consenso busca orientar al personal de salud en Venezuela en el abordaje terapéutico y la atención de las personas con COVID-19, estableciendo recomendaciones con base a la mejor evidencia para la fecha. Las recomendaciones no solo se limitan a definir qué opciones terapéuticas han mostrado mayor eficacia y seguridad, sino que determina cuáles drogas carecen todavía de suficiente evidencia, y qué alternativas no deberían utilizarse por carecer de beneficios y/o de seguridad establecida. La medicina basada en la evidencia busca fundamentar las decisiones clínicas con base en evidencias; que son todos los elementos y hechos que demuestran jerárquicamente el nivel de veracidad y validez de diversos planteamientos en medicina. El mayor nivel de evidencia terapéutica se construye por medio de metaanálisis y revisiones sistemáticas de la literatura con base en estudios clínicos controlados, prospectivos, con asignación al azar por doble ciego, y con una muestra lo suficientemente importante; y es este tipo de evidencia la que se ha considerado más relevante para establecer las recomendaciones.
About 80 % of symptomatic COVID-19 cases have mild to moderate illness, which does not usually progress to more advanced stages. 14 % of cases can progress in about 7 to 10 days to a severe pulmonary condition, while 6 % continue to deteriorate over time in the face of a hyperinflammatory response or cytokine storm, which leads to shock and failure of multiple organs. In general, individuals with risk factors such as age over 60 years, male gender, obesity, diabetes, hypertension, immunosuppression, solid organ transplantation, kidney disease, smoking, generally have a higher risk of progression. but that does not rule out the isolated possibility that apparently healthy individuals may present a severe evolution or various pulmonary, renal, cardiovascular, neurological, endocrinological complications, among others. This consensus seeks to guide health personnel in Venezuela in the therapeutic approach and care of people with COVID-19, establishing recommendations based on the best evidence to date. The recommendations are not only limited to defining which therapeutic options have shown greater efficacy and safety, but also determine which drugs still lack sufficient evidence, and which alternatives should not be used due to lack of benefits and / or established safety. Evidence-based medicine seeks to base evidencebased clinical decisions; which are all the elements and facts that hierarchically demonstrate the level of veracity and validity of various approaches in medicine. The highest level of therapeutic evidence is constructed through meta-analysis and systematic reviews of the literature based on controlled, prospective clinical studies, with double-blind randomization, and with a sufficiently large sample; and it is this type of evidence that has been considered most relevant to establish the recommendations.
ABSTRACT
The aim of this study was to evaluate the inflammation process that resulted from the inoculation of Wistar Rats with Acanthamoeba griffini, a virulent T3 Acanthamoeba genotype that produces keratitis. Haematoxylin and eosin, periodic acid stain, immunohistochemistry and morphometry were used to analyse tissues from rats of an Acanthamoeba keratitis (AK) model. Two weeks after inoculating the rats with A griffini trophozoites, the thickness of the stroma had diminished, followed by an increase in thickness at 4 weeks. At the latter time, an abundance of inflammatory infiltrate cells was observed, some found to express IL-1ß, IL-10 and/or caspase 3. Intercellular adhesion molecule-1 was expressed in corneal blood vessels amid the abundant vascularization characteristic of the development of AK. Through an immunohistochemical technique, trophozoites were detected at 2 and 4 weeks post-inoculation. By 8 weeks, there were a low number of trophozoites and cysts and the corneas of infected rats were similar in thickness to those of the controls. Thus, the rats were capable of healing experimental AK in the present rat model. Diverse immunological mechanisms regulated the inflammatory process in acute AK induced by A griffini in a murine model.
Subject(s)
Acanthamoeba Keratitis/pathology , Acanthamoeba/physiology , Acanthamoeba/classification , Acanthamoeba Keratitis/immunology , Animals , Apoptosis , Caspase 3/analysis , Cornea/pathology , Disease Models, Animal , Female , Humans , Intercellular Adhesion Molecule-1/analysis , Interleukin-10/analysis , Interleukin-1beta/analysis , Mice , Rats , Rats, Wistar , Trophozoites/physiologySubject(s)
Hypertension , Pre-Eclampsia , Female , Humans , Pregnancy , Pregnancy, High-Risk , Umbilical CordABSTRACT
Entamoeba histolytica is an invasive enteric protozoan, whose infections are associated to high morbidity and mortality rates. However, only less than 10% of infected patients develop invasive amebiasis. The ability of E. histolytica to adapt to the intestinal microenvironment could be determinant in triggering pathogenic behavior. Indeed, during chronic inflammation, the vagus nerve limits the immune response through the anti-inflammatory reflex, which includes acetylcholine (ACh) as one of the predominant neurotransmitters at the infection site. Consequently, the response of E. histolytica trophozoites to ACh could be implicated in the establishment of invasive disease. The aim of this study was to evaluate the effect of ACh on E. histolytica virulence. Methods include binding detection of ACh to plasma membrane, quantification of the relative expression of virulence factors by RT-PCR and western blot, evaluation of the effect of ACh in different cellular processes related to E. histolytica pathogenesis, and assessment of the capability of E. histolytica to migrate and form hepatic abscesses in hamsters. Results demonstrated that E. histolytica trophozoites bind ACh on their membrane and show a clear increase of the expression of virulence factors, that were upregulated upon stimulation with the neurotransmitter. ACh treatment increased the expression of L220, Gal/GalNAc lectin heavy subunit (170 kDa), amebapore C, cysteine proteinase 2 (ehcp-a2), and cysteine proteinase 5 (ehcp-a5). Moreover, erythrophagocytosis, cytotoxicity, and actin cytoskeleton remodeling were augmented after ACh treatment. Likewise, by assessing the formation of amebic liver abscess, we found that stimulated trophozoites to develop greater hamster hepatic lesions with multiple granulomas. In conclusion, ACh enhanced parasite pathogenicity by upregulating diverse virulence factors, thereby contributing to disease severity, and could be linked to the establishment of invasive amebiasis.
Subject(s)
Amebiasis , Entamoeba histolytica , Entamoebiasis , Liver Abscess, Amebic , Parasites , Acetylcholine , Animals , Cricetinae , Humans , Virulence , Virulence FactorsABSTRACT
Introducción: La vigilancia permanente de la calidad constituye un requerimiento ético y un compromiso de las universidades actuales, como garantía de la formación de profesionales con elevada sensibilidad social. Objetivo: Desarrollar un modelo de gestión de calidad en la educación a distancia, idóneo para la maestría de Gerencia en Salud para el Desarrollo Local, basado en las necesidades detectadas por los estudiantes y en las experiencias de buenas prácticas en esta modalidad. Métodos: Se realizó una investigación acción, con adaptación parcial de la metodología del marco lógico, en un posgrado administrado en la modalidad a distancia en la Universidad Técnica Particular de Loja, Ecuador. La experiencia se desarrolló mediante un diagnóstico de las debilidades académicas y administrativas de la maestría, a partir del cual se diseñó, implementó y evaluó un modelo de gestión de calidad, basado en las necesidades detectadas por los estudiantes, y en la revisión de estándares y experiencias de calidad. Asimismo, con un nivel de confianza de 95 por ciento, una precisión de 3 por ciento y una proporción de 5 por ciento, se calculó el tamaño muestral de 108 informantes, seleccionados al azar de una población de 230 estudiantes. Resultados: Los resultados indicaron que todos los elementos incluidos en el modelo fueron útiles para mejorar la calidad del programa. Sin embargo, se necesita continuar fortaleciendo la calidad de atención tutorial, especialmente en cuanto a los tiempos de respuesta, la afectividad de los mensajes y la empatía demostrada en los procesos de realimentación. Conclusiones: Es prioritario mejorar los aspectos administrativos implicados en las actividades presenciales, así como dar seguimiento continuo a los elementos del modelo mediante la ampliación de otros aspectos considerados en las teorías educativas y en los estándares de calidad nacional e internacional(AU)
Introduction: Permanent quality monitoring constitutes an ethical requirement and a commitment of universities nowadays, as a guarantee for the training of professionals with high social sensitivity. Objective: To develop a quality management model in distance education, suitable for the master's degree course in Health Management for Local Development, based on the needs detected by the students and experiences of good practices in this modality. Methods: An action research was carried out, with partial adaptation of the logical framework methodology, in a postgraduate course administered in the distance modality at Particular Technical University of Loja, Ecuador. The experience was developed through diagnosis of the academic and administrative weaknesses of the master's degree course, from which a quality management model was designed, implemented and evaluated, based on the needs detected by the students as well as the revision of quality standards and experiences. Likewise, with a confidence level of 95 percent, an accuracy of 3 percent, and a proportion of 5 percent, we calculated the sample size of 108 informants, randomly selected from a population of 230 students. Results: The results indicated that all the elements included in the model were useful to improve the quality of the program. However, it is necessary to continue strengthening the quality of tutorial attention, especially in terms of response times, the affectivity of messages, and the empathy demonstrated in the feedback processes. Conclusions: It is a priority to improve the administrative aspects involved in face-to-face activities, as well as to monitor continuously the elements of the model by expanding other aspects considered in educational theories and in national and international quality standards(AU)
Subject(s)
Humans , Education, Distance , Total Quality Management , Health Management , Methodology as a SubjectABSTRACT
La sarcoidosis es una enfermedad granulomatosa no caseificante, multisistémica, de causa desconocida, que compromete al pulmón y a los ganglios linfáticos mediastinales entre el 90 y el 95% de los casos. También puede afectar otros órganos, como las glándulas salivales, piel, ojos, hígado, bazo, corazón, huesos y sistema nervioso central. La sarcoidosis tiene una baja prevalencia en Latinoamérica y es subdiagnosticada debido a la alta frecuencia de otros trastornos similares, como tuberculosis, lepra y micosis profundas. El diagnóstico presuntivo se establece con hallazgos imagenológicos característicos dentro de un contexto clínico apropiado y se confirma con la evidencia histológica de granulomas no caseificantes de células epiteliales, en ausencia de otras etiologías. Los hallazgos torácicos incluyen la afectación pulmonar, ganglionar y bronquial, los cuales son detectados a través de la radiografía (Rx) y tomografía computada (TC) de tórax, siendo esa última más sensible y específica. En este artículo, resaltamos la importancia de reconocer los patrones de presentación típicos y atípicos de la sarcoidosis en Rx y TC, así como la relevancia de las imágenes torácicas como elemento clave en el algoritmo diagnóstico de esa patología. También describimos la utilidad de la resonancia magnética (RM), como método adicional para el diagnóstico en casos de afectación cardíaca y el papel de la tomografía por emisión de positrones (PET-CT) en el seguimiento terapéutico.
Sarcoidosis is a non-caseating granulomatous, multisystemic disease of unknown cause that involves the lung and mediastinal lymph nodes in 90-95% of cases. It can also affect other organs such as the salivary glands, skin, eyes, liver, spleen, heart, bones and the central nervous system. Sarcoidosis has a low prevalence in Latin America and it is underdiagnosed due to the high frequency of other similar disorders such as tuberculosis, leprosy and deep mycosis. The presumptive diagnosis is established based on characteristic imaging findings within an appropriate clinical setting and is confirmed by histological evidence of non-caseating epithelioid cell granulomas, in the absence of other etiologies. Thoracic imaging findings include pulmonary, nodal and bronchial involvement, which are detected on chest radiography (CXR) and computed tomography (CT), this last one having a higher sensitivity and specificity. In this article, we highlight the importance of recognizing the typical and atypical presentation patterns of sarcoidosis on CXR and CT, as well as the relevance of thoracic images as key elements in the diagnostic algorithm of this pathology. We also describe the usefulness of magnetic resonance (MR) imaging as an additional method for diagnosis in cases of cardiac involvement and the role of positron emission tomography (PET-CT) in therapeutic follow-up.
Subject(s)
Humans , Sarcoidosis , Sarcoidosis/diagnostic imaging , Magnetic Resonance Spectroscopy/methods , Radiography/methods , Tomography, X-Ray Computed/methods , Sarcoidosis, Pulmonary/diagnostic imaging , Positron-Emission Tomography/methods , Sarcoidosis/diagnosis , Radiography, ThoracicABSTRACT
La etiología que conduce al daño neonatal es multifactorial, y los procesos infecciosos pueden estar implicados en él. El objetivo de este estudio fue identificar microorganismos del tracto genital materno asociados con el daño neonatal, a fin de prevenir futuras complicaciones perinatológicas. Se estudiaron 711 embarazadas que concurrieron entre enero de 2010 y julio 2013 al consultorio externo de Obstetricia del Hospital de Clínicas de la UBA para sus controles prenatales, y cuyos partos también tuvieron lugar en dicho nosocomio. En la sangre del cordón umbilical se investigó la presencia de Ureaplasma urealyticum y Mycoplasma hominis mediante el cultivo con sustratos metabólicos (Micofast-Biomerieux), y la de Trichomonas vaginalis por PCR, con primers específicos. El estudio microbiológico del contenido vaginal se efectuó en 288 de las embarazadas en la semana 35 a 37. Se empleó la metodología convencional, a la que se agregó el cultivo en tioglicolato modificado para T. vaginalis. Se investigó la presencia de estreptococos grupo B (EGB) en hisopado anorrectaly de introito vaginal, utilizando enriquecimiento en caldo selectivo y posterior siembra en medio cromogénico. Se utilizaron los test de χ² Yates y de Fisher para muestras independientes, considerándose significativo p < 0,05. La vaginosis bacteriana (VB) se relacionó significativamente con el daño neonatal (p = 0,02), al igual que la presencia de M. hominis (p = 0,03) y de T. vaginalis (p = 0,03) en la sangre del cordón umbilical. Las complicaciones predominantes fueron el parto pretérmino, la rotura prematura de membrana (RPM), el bajo peso y un valor de Apgar <7. No se asoció al daño neonatal la presencia de U. urealyticum (p = 0,35) en el cordón umbilical, ni la de Candidaspp. (p = 0,94) o EGB (p = 0,18) en el tracto genital de las madres. Dado que ciertas alteraciones en la microbiota del tracto genital materno se relacionaron con el dano neonatal, consideramos de fundamental importancia realizar el estudio microbiológico del contenido vaginal durante el embarazo, para prevenir posibles complicaciones maternas y perinatológicas.
The etiology leading to neonatal damage is multifactorial, being genital infections one of the causes. The objective of the study was to identify microorganisms of the maternal genital tract that are associated with neonatal damage, in order to prevent future perinatal complications. Seven hundred and eleven pregnant patients attended their prenatal control during the period January 2010-July 2013. Ureaplasma urealyticum and Mycoplasma hominis presence was investigated in umbilical cord blood by metabolic substrates (Micofast-Biomerieux) and that of T. vaginalis, by PCR using specific primers. The microbiological study of the vaginal contents of 288 pregnant patients at weeks 35 to 37 was performed by conventional methods, adding the modified thioglycolate culture for T. vaginalis. Group B streptococcus (GBS) was investigated in anorectal and vaginal introitus swabs, using selective broth enrichment and subsequent isolation in chromogenic medium. The χ² Yates test and Fisher's test were used for independent samples. A p value <0.05 was considered statistically significant. The pathogens significantly related to neonatal damage were M. hominis (p = 0.03), T. vaginalis (p = 0.03), and BV (p = 0.02). Main complications were preterm birth, premature rupture of membranes (PRM), low weight and Apgar score <7. U. urealyticum (p = 0.35), Candidaspp. (p = 0.94) and GBS (p = 0.18) were not related to neonatal damage. Since different microorganisms of the maternal genital tract were related to neonatal damage, it is very important to perform the microbiological study of vaginal contents during pregnancy to prevent possible maternal and perinatal complications.