ABSTRACT
RESUMEN Introducción: La vitamina D, considerada más que una vitamina, una prohormona, se le atribuye múltiples e importantes funciones que van más allá de la homeostasis cálcica. El creciente interés por la vitamina D está relacionado con el descubrimiento de sus receptores y de la expresión de la enzima 1α-hidroxilasa en diferentes tejidos del organismo. Esto ha generado la descripción de un gran número de efectos de la vitamina D en diferentes tejidos y en diversos procesos fisiológicos como: actividad antitumoral, reparación del ácido desoxirribonucleico (DNA), control de la apoptosis, estrés oxidativo, inmunomodulación, adhesión celular y metabolismo y otras funciones aún por esclarecer, y aunque los estudios no son concluyentes, los mismos proponen una relación entre niveles bajos de la vitamina y algunas enfermedades crónicas, autoinmunes y oncológicas. Objetivo: El propósito del presente artículo es describir las funciones extraesqueléticas de la vitamina D y su relación con algunas enfermedades a partir de información actualizada. Método: Se utilizó como buscador de información científica el Google Académico. Se revisaron 101 artículos provenientes de diferentes bases de datos: PubMed, SciELO y páginas web en general; de los cuales fueron referenciados 74 documentos. Conclusiones: Existe evidencia del efecto extraóseo de la hormona vitamina D, así como de la influencia biológica desfavorable de sus bajos niveles, sin embargo, no existe consenso relativo al efecto beneficioso de la suplementación con esta hormona(AU)
ABSTRACT Introduction: Vitamin D, considered, more than a vitamin, a prohormone, is attributed multiple and important functions beyond calcium homeostasis. The growing interest in vitamin D is related to the discovery of its receptors and the expression of the 1α-hydroxylase enzyme in different body tissues. This has generated the description of a large number of effects of vitamin D in different tissues and it involvement in various physiological processes such as antitumor activity, DNA repair, control of apoptosis, oxidative stress, immunomodulation, cell adhesion, and metabolism, as well as other functions still to be clarified; and, although studies are not conclusive, they suggest a relationship between low levels in the vitamin and some chronic, autoimmune and oncological diseases. Objective: The purpose of this article was to describe, based on updated information, the extraskeletal functions of vitamin D and its relationship with some diseases. Methods: Google Scholar was the search engine used to retrieve scientific information. We reviewed 101 articles from different databases, such as PubMed, SciElo, and web pages in general. Out of this number, 74 were chosen as referents. Conclusions: There is evidence about the extra-bone effect of the hormone known as vitamin D, as well as about the unfavorable biological influence of its low levels; however, there is no consensus regarding the beneficial effect of supplementation with this hormone(AU)
Subject(s)
Humans , Vitamin D/administration & dosage , Homeostasis/drug effects , Review Literature as Topic , Databases, Bibliographic/trendsABSTRACT
BACKGROUND Calotropis procera latex protein fraction (LP) was previously shown to protect animals from septic shock. Further investigations showed that LP modulate nitric oxide and cytokines levels. OBJECTIVES To evaluate whether the protective effects of LP, against lethal bacterial infection, is observed in its subfractions (LPPII and LPPIII). METHODS Subfractions (5 and 10 mg/kg) were tested by i.p. administration, 24 h before challenging with lethal injection (i.p.) of Salmonella Typhimurium. LPPIII (5 mg/kg) which showed higher survival rate was assayed to evaluate bacterial clearance, histopathology, leukocyte recruitment, plasma coagulation time, cytokines and NO levels. FINDINGS LPPIII protected 70% of animals of death. The animals given LPPIII exhibited reduced bacterial load in blood and peritoneal fluid after 24 h compared to the control. LPPIII promoted macrophage infiltration in spleen and liver. LPPIII restored the coagulation time of infected animals, increased IL-10 and reduced NO in blood. MAIN CONCLUSIONS LPPIII recruited macrophages to the target organs of bacterial infection. This addressed inflammatory stimulus seems to reduce bacterial colonisation in spleen and liver, down regulate bacterial spread and contribute to avoid septic shock.
Subject(s)
Animals , Plant Proteins/therapeutic use , Salmonella Infections/drug therapy , Plant Extracts/pharmacology , Calotropis/chemistry , Homeostasis/drug effects , Inflammation/drug therapy , Latex/chemistry , Anti-Bacterial Agents/therapeutic use , Plant Proteins/isolation & purification , Plant Proteins/pharmacology , Salmonella Infections/immunology , Salmonella Infections/microbiology , Down-Regulation , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacologyABSTRACT
ABSTRACT Objective To study the effect of using a one time high dose "stoss therapy" of vitamin D2 (ergocalciferol: VD2) on indices of insulin sensitivity {whole body sensitivity index: WBISI} and secretion {insulinogenic index: IGI} measured during an oral glucose tolerance test (OGTT) in obese adolescents with VDD (25 OHD; serum metabolite of vit D: < 30 ng/dL). Subjects and methods In a randomized placebo controlled cross over design 20 obese adolescents with vitamin D deficiency (VDD) had baseline OGTT. Arm A received one time high dose 300,000 IU of ergocalciferol and Arm B received placebo. After 6 weeks the adolescents were reassigned to Arm A if they were in Arm B and vice versa. 25OHD, calcium, parathyroid hormone, comprehensive metabolic panel, urine calcium creatinine ratio were measured at each study visit. OGTTs to assess indices of sensitivity and secretion were done at baseline, 6 weeks and 12 weeks respectively. Results Adolescents were obese and insulin resistant (mean ± SD: mean age = 15.1 ± 1.9 years; BMI: 32.7 ± 9.8; homeostatic model of insulin resistance: HOMA-IR: 4.2 ± 2.8). Stoss therapy with VD2 increased 25OHD from baseline (16.7 ± 2.9 to 19.5 ± 4.5; p = 0.0029) when compared to the placebo. WBISI (2.8 ± 1.9) showed a trend towards improvement in Rx group (p = 0.0577) after adjustment for covariates. IGI (3 ± 2.2) showed an improvement in both Rx and placebo groups. Conclusions Our study demonstrated that using a high dose of VD2 (300,000 IU) did not have any beneficial effect on insulin sensitivity (whole body sensitivity index {WBISI}) and secretory indices (insulinogenic index {IGI}) in obese adolescents. High dose "stoss therapy" of VD2 did not appear to have any beneficial effect on glucose homeostasis on obese adolescents.
Subject(s)
Humans , Male , Female , Adolescent , Vitamin D Deficiency/drug therapy , Vitamins/administration & dosage , Ergocalciferols/administration & dosage , Pediatric Obesity/blood , Vitamin D Deficiency/complications , Vitamin D Deficiency/blood , Blood Glucose/drug effects , Insulin Resistance , Body Mass Index , Cross-Over Studies , Pediatric Obesity/complications , Glucose Tolerance Test , Homeostasis/drug effectsABSTRACT
ABSTRACT Considering that thiol-containing enzymes like kinases are critical for several metabolic pathways and energy homeostasis, we investigated the effects of cystine dimethyl ester and/or cysteamine administration on kinases crucial for energy metabolism in the kidney of Wistar rats. Animals were injected twice a day with 1.6 µmol/g body weight cystine dimethyl ester and/or 0.26 µmol/g body weight cysteamine from the 16th to the 20th postpartum day and euthanized after 12 hours. Pyruvate kinase, adenylate kinase, creatine kinase activities and thiol/disulfide ratio were determined. Cystine dimethyl ester administration reduced thiol/disulfide ratio and inhibited the kinases activities. Cysteamine administration increased the thiol/disulfide ratio and co-administration with cystine dimethyl ester prevented the inhibition of the enzymes. Regression between the thiol/disulfide ratio, and the kinases activities were significant. These results suggest that redox status may regulate energy metabolism in the rat kidney. If thiol-containing enzymes inhibition and oxidative stress occur in patients with cystinosis, it is possible that lysosomal cystine depletion may not be the only beneficial effect of cysteamine administration, but also its antioxidant and thiol-protector effect.
Subject(s)
Animals , Sulfhydryl Compounds , Cysteamine/pharmacology , Cystine/analogs & derivatives , Disulfides , Homeostasis/drug effects , Kidney/drug effects , Adenylate Kinase/analysis , Adenylate Kinase/drug effects , Reproducibility of Results , Rats, Wistar , Creatine Kinase/analysis , Creatine Kinase/drug effects , Cystine/pharmacology , Cystine Depleting Agents/pharmacologyABSTRACT
Abstract Background: Osteoradionecrosis of the jaw (ORNJ) is the most severe and complex sequel of head and neck radiotherapy (RT) because of the bone involved, it may cause pain, paresthesia, foul odor, fistulae with suppuration, need for extra oral communication and pathological fracture. We treated twenty lesions of ORNJ using low-level laser therapy (LLLT) and antimicrobial photodynamic therapy (aPDT). The objective of this study was to stimulate the affected area to homeostasis and to promote the healing of the oral mucosa. Methods: We performed aPDT on the exposed bone, while LLLT was performed around the bone exposure (red spectrum) and on the affected jaw (infrared spectrum). Monitoring and clinical intervention occurred weekly or biweekly for 2 years. Results: 100% of the sample presented clinical improvement, and 80% presented complete covering of the bone exposure by intact oral mucosa. Conclusion: LLLT and aPDT showed positive results as an adjuvant therapy to treat ORNJ.
Subject(s)
Humans , Male , Female , Adult , Aged , Osteoradionecrosis/therapy , Photochemotherapy/methods , Jaw Diseases , Low-Level Light Therapy/methods , Chemoradiotherapy, Adjuvant/methods , Anti-Infective Agents/therapeutic use , Osteoradionecrosis/pathology , Time Factors , Wound Healing/radiation effects , Jaw Diseases/pathology , Prospective Studies , Reproducibility of Results , Treatment Outcome , Dose-Response Relationship, Radiation , Homeostasis/drug effects , Homeostasis/radiation effects , Middle Aged , Mouth Mucosa/drug effects , Mouth Mucosa/radiation effectsABSTRACT
The aim of this study was to perform a literature review regarding the role of hyaluronic acid (HA) in the homeostasis and therapeutics of temporomandibular joint (TMJ) osteoarthritis (OA). The TMJ has characteristics that give it special adaptation and recovery abilities, where HA plays a fundamental role in helping to maintain joint homeostasis, which is affected in pathological processes like OA. OA is a chronic degenerative multi-factor disease that can affect all the components of the synovial joints, causing degradation of the articular cartilage, extracellular matrix and breakage in the HA molecules. HA is a non-branched linear polysaccharide with viscosupplementation, anti-inflammatory, lubrication and pain relief effects; it also activates the intrinsic repair processes of the cartilage and normalizes the endogenous production of HA by the synoviocytes. In recent years, the therapeutic use of HA has shown evidence that supports its application in TMJ OA, improving viscosupplementation capacity, acting at the cellular and molecular levels, reducing various inflammatory mediators and improving the reparative characteristics. Its use has been studied in animal models and in humans. However, no consensus has been reached in terms of concentrations, dose, application frequency or molecular weight to be used.
El objetivo de este estudio fue realizar una revisión de la literatura respecto del rol del ácido hialurónico (AH) en la homeostasis y terapéutica de la osteoartritis (OA) de la articulación temporomandibular (ATM). La ATM presenta características que le confieren propiedades de adaptación y recuperación especiales, donde el AH juega un rol fundamental ayudando a mantener la homeostasis articular, la cual se ve afectada en procesos patológicos como la OA. La OA es una enfermedad multifactorial crónica degenerativa que puede afectar a todos los componentes de las articulaciones sinoviales, generando degradación del cartílago articular, matriz extracelular y quiebre de las moléculas de AH. El AH es un polisacárido lineal no ramificado que presenta efectos de viscosuplementación, antiinflamatorios, lubricantes, en el alivio del dolor, permite además, activar procesos intrínsecos de reparación del cartílago y normalizar la producción endógena de AH por parte de los sinoviositos. En los últimos años el uso terapéutico del AH ha presentado evidencia que sustenta su aplicación en OA de ATM mejorando la capacidad de viscosuplementación, actuando a nivel celular y molecular, disminuyendo diversos mediadores inflamatorios y mejorando las características reparativas. Su uso se ha estudiado en modelos animales y en humanos, sin embargo no existe consenso en cuanto a concentraciones, dosis, frecuencias de aplicación y peso molecular a utilizar.
Subject(s)
Osteoarthritis/drug therapy , Temporomandibular Joint Disorders/drug therapy , Viscosupplementation/methods , Hyaluronic Acid/administration & dosage , Temporomandibular Joint/drug effects , Homeostasis/drug effectsABSTRACT
Abstract: Purpose: To investigate the microbiological, inflammatory and oxidant effects of adjuvant ozone administration in experimental rat vascular graft infection model which has not been previously investigated. Methods: Forty adult Wistar rats were divided into Sham, Control, Vancomycin, Ozone, Vancomycin+Ozone groups. Grafts were inoculated with Methicillin-resistant Staphylococcus aureus (MRSA) strain and implanted subcutaneously. Rats were treated intraperitoneally with ozone and /or intramuscularly with vancomycin for 10 days. Grafts were evaluated by quantitative bacterial cultures. Blood samples were harvested for determination of thiol-disulphide and cytokine profiles. Results: There was no significant difference in bacterial counts between Control and Ozone Groups. In the Ozone Group median colony count was significantly higher than the Vancomycin and Vancomycin+Ozone Groups. Total thiol and disulphide levels increased and disulphide/native thiol and disulphide/total thiol ratios decreased in Ozone Group significantly. Albumin levels decreased significantly in Vancomycin and Vancomycin+Ozone Groups compared to the Sham Group. IL-1 and TNF-alpha levels significantly increased in infected rats. Decreased levels of VEGF due to infection reversed by ozone therapy in control and vancomycin groups. Conclusions: We didn't observe any benefit of the agent on MRSA elimination in our model. Likewise, effects of ozone on thiol-disulphide homeostasis and inflammatory cytokines were contradictory.
Subject(s)
Animals , Male , Oxidants, Photochemical/pharmacology , Ozone/pharmacology , Staphylococcal Infections/drug therapy , Disulfides/blood , Methicillin-Resistant Staphylococcus aureus/drug effects , Vascular Grafting , Reference Values , Time Factors , Vascular Diseases/microbiology , Serum Albumin/analysis , Vancomycin/pharmacology , Colony Count, Microbial , Random Allocation , Reproducibility of Results , Cytokines/blood , Treatment Outcome , Rats, Wistar , Transplants/microbiology , Methicillin-Resistant Staphylococcus aureus/growth & development , Homeostasis/drug effects , Anti-Bacterial Agents/pharmacologyABSTRACT
ABSTRACT PURPOSE: To evaluate metabolic effects in experimental model of glucocorticoid-induced insulin resistance. METHODS: Twenty Wistar male rats were randomly divided into two groups, which were treated with intraperitoneally injected dexamethasone 1mg/Kg/day for ten days consecutively (Group D; n=10) and placebo (Group C; n=10). The variables analyzed were: from the first to the 10th day - body weight (before and after treatment); food and water daily consumption; on the 10th day - glycemia, insulinemia, HOMA-beta and HOMA-IR. The blood samples for laboratory analysis were obtained by intracardiac puncture. Also on the 10th day liver fragments were taken for analyzing glycogen and fattty. RESULTS: Group D animals compared to group C had: weight reduction (g), (D=226.5±24.7 vs C=295.0±25.4; p=0.001); increased glycemia (mmol/l) (D=19.5±2.1 vs C=14.2±3.1; p=0.0001); diminished insulinemia (mU/l) (D=0.2±0.1 vs C=2.0±0.4; p=0.0001); reduced HOMA-β (D=0.2±0.1 vs C=4.2±1.7; p=0.0002); diminished HOMA-IR (D=0.2±0.1 vs C=1.3±0.4; p=0.0002). Histological examination of the liver showed that 100% of group D and none of group C had moderate fatty. (p=0.2). CONCLUSION: Animals treated with glucocorticoid, in this experimental model, expressed hyperglycemia, hypoinsulinism and decreased peripheral insulin sensitivity.
Subject(s)
Animals , Male , Insulin Resistance , Dexamethasone/adverse effects , Glucocorticoids/adverse effects , Blood Glucose/analysis , Body Weight , Random Allocation , Rats, Wistar , Diabetes Mellitus/chemically induced , Disease Models, Animal , Homeostasis/drug effects , Hyperglycemia/chemically induced , Liver/drug effectsABSTRACT
Abstract: INTRODUCTION There is an increasing burden of multidrug resistance. As a result, deciphering the mechanisms of action of natural compounds with antifungal activity has gained considerable prominence. We aimed to elucidate the probable mechanism of action of citronellal, a monoterpenoid found in the essential oil extracted from Cymbopogon plants, against Candida albicans. METHODS Drug susceptibility was measured by broth microdilution and spot assays. Ergosterol levels were estimated using the alcoholic potassium hydroxide method and H+ extrusion was assessed by monitoring the glucose-induced acidification of the external medium. Virulence traits were studied by hyphal morphogenesis and biofilm formation, along with fungal cell adherence to polystyrene surface and human oral epithelial cells. RESULTS Citronellal showed anticandidal activity against C. albicans and non-albicans species of Candida at a minimum inhibitory concentration of 1 mg/ml. Citronellal interfered with membrane homeostasis, which is the major target of known antifungal drugs, by increasing the hypersensitivity of the fungi to membrane-perturbing agents, reducing ergosterol levels, and diminishing glucose-induced H+ extrusion. In addition, oxidative and genotoxic stresses were induced via an increased production of reactive oxygen species. Furthermore, citronellal inhibited the virulent attributes of yeast-to-hypha transition and biofilm formation. It also reduced cell adherence to polystyrene surface and the human oral epithelial cells. CONCLUSIONS This is the first study to propose the cell membrane, morphogenetic switching, biofilm formation, and cell adherence of Candida albicans as potential targets for the anticandidal activity of citronellal. However, clinical investigations on the therapeutic applications of citronellal are required.
Subject(s)
Humans , Virulence/drug effects , Candida albicans/drug effects , Monoterpenes/pharmacology , Aldehydes/pharmacology , Homeostasis/drug effects , Antifungal Agents/pharmacology , Candida albicans/pathogenicity , Microbial Sensitivity Tests , Cell Adhesion/drug effects , Biofilms/growth & development , Biofilms/drug effects , Acyclic MonoterpenesABSTRACT
BACKGROUND: Heavy metals can cause great harm to Siberian tigers in the natural environment. Cadmium (Cd2+) is an environmental contaminant that affects multiple cellular processes, including cell proliferation, differentiation, and survival. It has been shown to induce apoptosis in a variety of cell types and tissues. RESULTS: We investigated the apoptotic effects of Cd2+ on Siberian tiger fibroblasts in vitro. Our research revealed the typical signs of apoptosis after Cd²+ exposure. Apoptosis was dose- (0-4.8 µM) and duration-dependent (12-48 h), and proliferation was strongly inhibited. Cd²+ increased the activity of caspase-3, -8, and -9 and disrupted calcium homeostasis by causing oxidative stress and mitochondrial dysfunction. It also increased K+ efflux and altered the mRNA levels of Bax, Bcl-2, caspase-3, caspase-8, Fas, and p53. CONCLUSIONS: Our results suggest that Cd2+ triggers the apoptosis of Siberian tiger fibroblasts by disturbing intracellular homeostasis. These results will aid in our understanding of the effects of Cd2+ on Siberian tigers and in developing interventions to treat and prevent cadmium poisoning.
Subject(s)
Animals , Cadmium/toxicity , Apoptosis/drug effects , Intracellular Space/drug effects , Tigers , Fibroblasts/drug effects , Homeostasis/drug effects , Siberia , DNA Damage , Cell Cycle/drug effects , Cells, Cultured , Polymerase Chain Reaction , Reactive Oxygen Species/analysis , Apoptosis/genetics , Caspases/analysis , Caspases/drug effects , Comet Assay/veterinary , Microscopy, Electron, Transmission , Reverse Transcription , Membrane Potential, Mitochondrial/drug effects , Fibroblasts/physiology , Homeostasis/physiologyABSTRACT
OBJETIVO: Investigar a influência de anticoncepcionais hormonais (ACH) orais em indicadores bioquímicos relacionados à utilização metabólica e distribuição de zinco e ao turnover ósseo em mulheres adultas jovens.MÉTODOS: Estudo transversal. Amostras de sangue e urina de não usuárias (-ACH; controle; n=69) e usuárias há pelo menos três meses de contraceptivos hormonais orais (+ACH; n=62) foram coletadas em condições padronizadas. Foram analisados os indicadores de homeostase de zinco e de turnoverósseo em soro ou plasma (zinco total e nas frações de albumina e α2-macroglobulina, albumina e atividade de fosfatase alcalina total e de origem óssea), em eritrócitos (zinco e metalotioneína) e em urina (zinco, cálcio e hidroxiprolina). Ingestões habituais de zinco e cálcio foram avaliadas por questionário de frequência de consumo.RESULTADOS: A ingestão alimentar de zinco foi semelhante nos grupos e, em média, acima do recomendado, enquanto que a ingestão de cálcio foi similarmente subadequada em +ACH e -ACH. Comparadas às controles, as +ACH apresentaram menores concentrações de zinco em soro, total e ligado à α2-macroglobulina (11 e 28,5%, respectivamente, p<0,001); albumina em soro (13%, p<0,001); atividade de fosfatase alcalina em plasma, total e de origem óssea (13 e 18%, respectivamente, p<0,05); metalotioneína em eritrócitos (13%, p<0,01) e zinco urinário (34%, p<0,05).CONCLUSÕES: O uso de ACH reduz o zinco sérico, altera a distribuição de zinco nas principais proteínas ligantes do soro com possíveis efeitos na captação tecidual, aumenta a retenção de zinco no organismo e reduz o turnover ósseo. O uso prolongado de ACH poderia levar a menor pico de massa óssea e/ou prejudicar a manutenção de massa óssea em mulheres jovens, principalmente com ingestão marginal de cálcio. Os efeitos de ACH verificados foram mais evidentes nas mulheres <25 anos de idade e nas nulíparas, as quais merecem especial atenção em estudos posteriores.
PURPOSE: To investigate the influence of the use of oral hormonal contraceptive agents (OCA) on the biochemical indices related to metabolic zinc utilization and distribution, and to bone turnover in young adult women.METHODS: Cross-sectional study. Blood and urine samples from non-users (-OCA; control; n=69) and users of hormonal contraceptives for at least 3 months (+OCA; n=62) were collected under controlled conditions. Indices of zinc homeostasis and of bone turnover were analyzed in serum or plasma (total, albumin-bound and α2-macroglobulin-bound zinc, albumin and total and bone alkaline phosphatase activity), in erythrocytes (zinc and metallothionein) and in urine (zinc, calcium and hydroxyproline). The habitual zinc and calcium intakes were evaluated by a food frequency questionnaire.RESULTS: Dietary zinc intake was similar in both groups and on average above recommended values, whereas calcium intake was similarly sub-adequate in +OCA and -OCA. Compared to controls, +OCA had lower concentrations of total and α2-macroglobulin-bound zinc (11 and 28.5%, respectively, p<0.001), serum albumin (13%, p<0.01), total and bone-specific alkaline phosphatase activity (13 and 18%, respectively, p<0.05), erythrocyte metallothionein (13%, p<0.01), and, urinary zinc (34%, p<0.05).CONCLUSIONS: OCA use decreases serum zinc, alters zinc distribution in major serum fractions with possible effects on tissue uptake, enhances zinc retention in the body and decreases bone turnover. Prolonged OCA use may lead to lower peak bone mass and/or to impaired bone mass maintenance in young women, particularly in those with marginal calcium intake. The observed OCA effects were more evident in women younger than 25 years and in nulliparous women, deserving special attention in future studies.
Subject(s)
Humans , Female , Adult , Young Adult , Bone Remodeling/drug effects , Contraceptives, Oral, Hormonal/pharmacology , Homeostasis/drug effects , Zinc/physiology , Contraceptive Agents , Cross-Sectional StudiesABSTRACT
El objetivo fue explicar la asociación entre las alteraciones en la homeostasis del zinc, algunas vitaminas y las repercusiones hepática, pancreática y alveolar, en individuos; que por ser tanto bebedores como fumadores, suman en su organismo las acciones tóxicas del etanol y del humo del tabaco. Los datos obtenidos indicaron que la ingestión elevada de alcohol da lugar a hipocincemia (menos de 10 µmoles/L), y esto a disfunciones: hepática, con aprovechamiento insuficiente de la vitamina A y del ácido fólico; hepática y pancreática, con baja biodisponibilidad de vitamina C y represión de la expresión de las enzimas colagenasas. El consumo excesivo de alcohol y la aspiración continuada del humo del tabaco, dio lugar al desplazamiento de la homeostasis del zinc hacia una hipocincemia severa (menos de 5 µmoles/L), se añadió a las anteriores la disfunción alveolar con represión de la expresión de la interleuquina-10, y un déficit en el nivel serológico de Vitamina C. Los procesos inflamatorios en hígado, páncreas y alveolos manifestaron como eventos patológicos comunes, la producción en exceso de especies reactivas del oxígeno y la manifestación de estrés oxidativo.
The purpose of the study was to explain the association between altered homeostasis of zinc and some vitamins and its hepatic, pancreatic and alveolar repercussions in smokers and drinkers. These individuals bring into their bodies the toxic action of ethanol and tobacco smoke. The data obtained show that high alcohol intake causes hypozincemia (less than 10 µmol/L), resulting in hepatic dysfunction, with insufficient vitamin A and folic acid absorption; hepatic and pancreatic dysfunction, with low vitamin C bioavailability; and repression of collagenase enzyme expression. Excessive alcohol consumption and the continual inhalation of tobacco smoke resulted in displacement of zinc homeostasis toward severe hypozincemia (less than 5 µmol/L), alveolar dysfunction with repression of interleukin-10 expression and low vitamin C serological levels. Common pathological events associated with inflammatory processes of the liver, pancreas and alveoli were the excessive production of reactive oxygen species and the manifestation of oxidative stress.
Subject(s)
Humans , Tobacco Use Disorder/complications , Oxidative Stress/drug effects , Alcoholism/complications , Homeostasis/drug effectsABSTRACT
The physiological role of C-reactive protein (CRP), the classical acute-phase protein, is not well documented, despite many reports on biological effects of CRP in vitro and in model systems in vivo. It has been suggested that CRP protects mice against lethal toxicity of bacterial infections by implementing immunological responses. In Achatina fulica CRP is a constitutive multifunctional protein in haemolymph and considered responsible for their survival in the environment for millions of years. The efficacy of Achatina CRP (ACRP) was tested against both Salmonella typhimurium and Bacillus subtilis infections in mice where endogenous CRP level is negligible even after inflammatory stimulus. Further, growth curves of the bacteria revealed that ACRP (50 µg/mL) is bacteriostatic against gram negative salmonellae and bactericidal against gram positive bacilli. ACRP induced energy crises in bacterial cells, inhibited key carbohydrate metabolic enzymes such as phosphofructokinase in glycolysis, isocitrate dehydrogenase in TCA cycle, isocitrate lyase in glyoxylate cycle and fructose-1,6-bisphosphatase in gluconeogenesis. ACRP disturbed the homeostasis of cellular redox potential as well as reduced glutathione status, which is accompanied by an enhanced rate of lipid peroxidation. Annexin V-Cy3/CFDA dual staining clearly showed ACRP induced apoptosis-like death in bacterial cell population. Moreover, immunoblot analyses also indicated apoptosis-like death in ACRP treated bacterial cells, where activation of poly (ADP-ribose) polymerase-1 (PARP) and caspase-3 was noteworthy. It is concluded that metabolic impairment by ACRP in bacterial cells is primarily due to generation of reactive oxygen species and ACRP induced anti-bacterial effect is mediated by metabolic impairment leading to apoptosis-like death in bacterial cells.
Subject(s)
Animals , Anti-Bacterial Agents/pharmacology , Apoptosis/drug effects , Bacillus subtilis/drug effects , Bacillus subtilis/metabolism , C-Reactive Protein/isolation & purification , C-Reactive Protein/pharmacology , Gluconeogenesis/drug effects , Glycolysis/drug effects , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/metabolism , Gram-Negative Bacterial Infections/microbiology , Hemolymph/metabolism , Homeostasis/drug effects , Immunoblotting , Lipid Peroxidation/drug effects , Male , Mice , Oxidation-Reduction , Reactive Oxygen Species/metabolism , Salmonella Infections/drug therapy , Salmonella Infections/metabolism , Salmonella Infections/microbiology , Salmonella typhimurium/drug effects , Salmonella typhimurium/metabolism , SnailsABSTRACT
Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.
Subject(s)
Animals , Rats , /pharmacology , Body Fluids/drug effects , Homeostasis/drug effects , Parabrachial Nucleus/drug effects , /administration & dosage , Body Fluids/physiology , Captopril/administration & dosage , Captopril/pharmacology , Drinking/drug effects , Furosemide/administration & dosage , Furosemide/pharmacology , Homeostasis/physiology , Imidazoles/administration & dosage , Imidazoles/pharmacology , Parabrachial Nucleus/physiology , Sodium Chloride, DietaryABSTRACT
Background: The venom of the family Viperidae, including the saw-scaled viper, is rich in serine proteinases and metalloproteinases, which affect the nervous system, complementary system, blood coagulation, platelet aggregation and blood pressure. One of the most prominent effects of the snake venom of Echis carinatus (Ec) is its coagulation activity, used for killing prey. Materials and methods: Subfractions F1A and F1B were isolated from Ec crude venom by a combination of gel chromatography (Sephadex G-75) and ion exchange chromatography on a DEAE-Sepharose (DE-52). These subfractions were then intravenously (IV) injected into NIH male mice. Blood samples were taken before and after the administration of these subfractions. Times for prothrombin, partial thromboplastin and fibrinogen were recorded. Results and conclusions: Comparison of the prothrombin time before and after F1A and F1B administrations showed that time for blood coagulation after injection is shorter than that of normal blood coagulation and also reduced coagulation time after Ec crude venom injection. This difference in coagulation time shows the intense coagulation activity of these subfractions that significantly increase the coagulation cascade rate and Causes to quick blood coagulation. The LD50 of the Ec crude venom was also determined to be 11.1 µg/mouse. Different crude venom doses were prepared with physiological serum and injected into four mice. Comparison of the prothrombin times after injection of subfractions F1A and F1B showed that the rate of mouse blood coagulation increases considerably. Comparing the partial thromboplastin times after injecting these subfractions with this normal test time showed that the activity rate of intrinsic blood coagulation system rose sharply in mice. Finally, by comparing the fibrinogen time after subfraction injections and normal test time, we can infer intense activation of coagulation cascade and fibrin production.(AU)
Subject(s)
Male , Mice , Blood Coagulation/physiology , Elapid Venoms/administration & dosage , Elapid Venoms/blood , Homeostasis/drug effects , Blood Coagulation Tests/methods , Chromatography, Ion Exchange/methods , Elapid Venoms/isolation & purification , Lethal Dose 50ABSTRACT
Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-alpha-dependent manner. We investigated whether a PPARalpha agonist, fenofibrate, exhibits an additive or synergistic effect on glucose metabolism, independent of its lipid-lowering effect, when added to metformin. Non-obese diabetic Goto-Kakizaki (GK) rats were divided into four groups and treated for 28 days with metformin, fenofibrate, metformin plus fenofibrate or vehicle. The random blood glucose levels, body weights, food intake and serum lipid profiles were not significantly different among the groups. After 4 weeks, metformin, but not fenofibrate, markedly reduced the blood glucose levels during oral glucose tolerance tests, and this effect was attenuated by adding fenofibrate. Metformin increased the expression of the GLP-1 receptor in pancreatic islets, whereas fenofibrate did not. During the intraperitoneal glucose tolerance tests with the injection of a GLP-1 analog, metformin and/or fenofibrate did not alter the insulin secretory responses. In conclusion, fenofibrate did not confer any beneficial effect on glucose homeostasis but reduced metformin's glucose-lowering activity in GK rats, thus discouraging the addition of fenofibrate to metformin to improve glycemic control.
Subject(s)
Animals , Male , Rats , Blood Glucose/metabolism , Body Weight/drug effects , Diabetes Mellitus, Experimental/drug therapy , Drug Therapy, Combination , Feeding Behavior/drug effects , Fenofibrate/pharmacology , Glucagon-Like Peptide 1/agonists , Glucose/metabolism , Glucose Tolerance Test , Homeostasis/drug effects , Immunohistochemistry , Injections, Intraperitoneal , Insulin-Secreting Cells/drug effects , Lipid Metabolism/drug effects , Metformin/pharmacology , Peptides/administration & dosage , Receptors, Glucagon/metabolism , Venoms/administration & dosageABSTRACT
The Thyroid gland with two symmetrical lobes has an important role in metabolism of the body and regulating of calcium. Any factor making structural and hormonal changes in this gland can produce metabolic disorders. To investigate the functional changes of the thyroid gland following coadministration of soy extract and Vitamin D3, 42 mature female mice in 7 groups were studied for 35 days. Two doses of soy extract [5 and 10 g/kgBW/day]; two doses of Vitamin D3 [100 and 200 micro g/kgBW/day]; and, a combination of both soy extract and Vitamin D3 with two doses were fed to each mouse by gavage. At the end of the feeding trial, following anesthetizing by diethyl ether, mice were bled. Serum levels of calcium were determined by method Colorimetry, and serum concentrations of T3, T4, TSH were determined by method Radio Immuno Assay. Data was statistically analyzed by the one way ANOVA test and significant differences were observed between groups [p<0.001]. Results showed the occurrence of a dose-dependent hypothyroidism in mice receiving only soy extract. In mice receiving only vitamin D3, significant and dose dependent increases of calcium levels, significant and dose-dependent decreases of TSH levels and, insignificant decreases in serum concentrations of T3 and T4 were observed. Finally, groups receiving a combination of high doses of soy extract and Vitamin D3, showed hypothyroidism. In conclusion, this study suggests that co-administration of soy extract and Vitamin D3, only in low doses, can balance the effects of individual use of these components on thyroid function and calcium homeostasis
Subject(s)
Animals, Laboratory , Soybeans , Cholecalciferol/pharmacology , Hypothyroidism , Analysis of Variance , Colorimetry , Homeostasis/drug effects , Thyroid Hormones , Mice , Calcium/bloodABSTRACT
PURPOSE: Ca2+ homeostasis plays an important role in myocardial cell injury induced by hypoxia-reoxygenation, and prevention of intracellular Ca2+ overload is key to cardioprotection. Even though thiopental is a frequently used anesthetic agent, little is known about its cardioprotective effects, particulary in association with Ca2+ homeostasis. We investigated whether thiopental protects cardiomyocytes against hypoxia-reoxygenation injury by regulating Ca2+ homeostasis. MATERIALS AND METHODS: Neonatal rat cardiomyocytes were isolated. Cardiomyocytes were exposed to different concentrations of thiopental and immediately replaced in the hypoxic chamber to maintain hypoxia. After 1 hour of exposure, a culture dish was transferred to the CO2 incubator and cells were incubated at 37degrees C for 5 hours. At the end of the experiments, the authors assessed cell protection using immunoblot analysis and caspase activity. The mRNA of genes involved in Ca2+ homeostasis, mitochondrial membrane potential, and cellular Ca2+ levels were examined. RESULTS: In thiopental-treated cardiomyocytes, there was a decrease in expression of the proapoptotic protein Bax, caspase-3 activation, and intracellular Ca2+ content. In addition, both enhancement of anti-apoptotic protein Bcl-2 and activation of Erk concerned with survival were shown. Furthermore, thiopental attenuated alterations of genes involving Ca2+ regulation and significantly modulated abnormal changes of NCX and SERCA2a genes in hypoxia-reoxygenated neonatal cardiomyocytes. Thiopental suppressed disruption of mitochondrial membrane potential (Delta Psi m) induced by hypoxia-reoxygenation. CONCLUSION: Thiopental is likely to modulate expression of genes that regulate Ca2+ homeostasis, which reduces apoptotic cell death and results in cardioprotection.
Subject(s)
Animals , Rats , Apoptosis , Calcium/metabolism , Cell Hypoxia/physiology , Cell Survival/drug effects , Cells, Cultured , GABA Modulators/pharmacology , Homeostasis/drug effects , Immunoblotting , In Situ Nick-End Labeling , Membrane Potential, Mitochondrial/drug effects , Microscopy, Confocal , Myocytes, Cardiac/drug effects , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Thiopental/pharmacologyABSTRACT
Central obesity have an important impact on the development of risk factors for coronary heart disease, including dislipidemia, glucose intolerance, insulin resistance and hypertension. These factors contribute to building cardiovascular (CV) disease as a major cause of death. The approach to obesity therapy should be designed to reduce CV risk and mortality. Diet and lifestyle changes remain the cornerstones of therapy for obesity, but the resultant weight loss is often small and long-term success is uncommon and disappointing. Drug therapy is considered for individuals with a body mass index greater than 30 kg/m² or ranging from 25 to 30 kg/m² if they have comorbid conditions. Antiobesity agents can be helpful to some patients in achieving and maintaining meaningful weight loss, but yet our pharmaceutical tools are of limited effectiveness considering the magnitude of the problem. At the present, only two drugs, orlistat and sibutramine, are approved for long-term treatment of obesity and promote no more than 5 to 10 percent of weight loss. Rimonabant, a cannabinoid-1 receptor antagonist, was withdrawn from the market because of concerns about its safety, including risk of suicidal and seizures, although very effective in promoting clinically meaningful weight loss, reduction in waist circumference, and improvements in several metabolic risk factors, rimonabant, a cannabinoid-1 receptor antagonist was withdrawn from the market because it concerns about its safety, including risk of suicidal and seizures. Fortunately, recent fundamental insights into the neuroendocrine mechanisms regulating body weight provide an expanding list of molecular targets for novel, rationally designed antiobesity drugs. In this review, the therapeutic potential of some antiobesity molecules in the development will be analyzed based on an understanding of energy homeostasis.
Obesidade e, particularmente, a obesidade central têm influência importante na predisposição a fatores de risco para doença coronariana, incluindo dislipidemia, intolerância à glicose, resistência à insulina e hipertensão. Tais fatores contribuem para tornar as doenças cardiovasculares (DC) causas frequentes de morte. Os métodos de tratamento da obesidade deveriam ser voltados à redução do risco e da mortalidade devido às doenças cardiovasculares. Dietas e mudanças no estilo de vida continuam sendo fatores-chave no tratamento à obesidade, mas a perda de peso resultante é geralmente pequena e o sucesso em longo prazo costuma ser incomum e frustrante. O tratamento com medicamentos é indicado para indivíduos com índice de massa corpórea superior a 30 kg/m² ou entre 25 e 30 kg/m², se apresentarem comorbidades. Agentes antiobesidade podem ajudar alguns pacientes a alcançar e manter uma perda de peso significativa, mas, ainda assim, os agentes farmacológicos são pouco efetivos considerando-se a magnitude do problema. Atualmente, apenas duas drogas, orlistat e sibutramina, são consideradas efetivas para tratamentos em longo prazo, promovendo não mais do que 5 por cento a 10 por cento de perda de peso. Embora seja muito eficaz ao promover perda de peso significativa do ponto de vista clínico, redução da circunferência da cintura e melhora no perfil metabólico, o rimonabanto, um antagonista do receptor canabinoide 1, foi retirado do mercado por fatores relacionados à segurança, incluindo a ocorrência de suicídios e convulsões. Felizmente, conhecimentos fundamentais recentes sobre mecanismos neuroendócrinos que regulam o peso corporal forneceram uma lista considerável de alvos moleculares para novas drogas antiobesidade produzidas racionalmente. Nesta revisão de literatura, a eficácia terapêutica de algumas moléculas antiobesidade será analisada com base no entendimento da homeostase energética.
Subject(s)
Animals , Humans , Anti-Obesity Agents/therapeutic use , Obesity/drug therapy , Weight Loss , Anti-Obesity Agents/pharmacology , Eating/physiology , Energy Metabolism/drug effects , Energy Metabolism/physiology , Homeostasis/drug effects , Homeostasis/physiology , Neuropeptides/physiology , Obesity/metabolismABSTRACT
Di-n-butyl phthalate (DBP) is a ubiquitous environmental pollutant, extensively used as a softener for polyvinyl chloride resins. A study was conducted to evaluate its effect on reproductive function of Wistar rats. DBP was given orally at a dose of 500, 1000 and 1500 mg kg(-1) body weight for 7 days. Evaluating histological and fertility parameters assessed reproductive function. Significant reduction in seminiferous tubule diameter, Leydig cell nuclear diameter (except at dose 500 mg), number of primary spermatocytes, secondary spermatocytes and spermatids were observed. Caudal sperm density and viability reduced significantly. Decrease in serum testosterone was also observed. Evidence indicates that DBP exposure causes dose dependent testicular toxicity and has the potential to induce adverse effect.