Proteomic analysis of endothelial cells and extracellular vesicles in response to indoxyl sulfate: Mechanisms of endothelial dysfunction in chronic kidney disease.

AIMS: Cardiovascular pathology is the main cause of death in chronic kidney disease (CKD) patients. CKD is associated with the accumulation of uremic toxins in the bloodstream, and indoxyl sulfate (IS) is one of the most abundant uremic toxins found in the blood of CKD patients. We conducted an in vitro study to assess the mechanisms underlying the IS-induced endothelial dysfunction that could lead to cardiovascular diseases. We also studied their extracellular vesicles (EVs) owing to their capacity to act as messengers that transmit signals through their cargo. MAIN METHODS: EVs were characterized by nanoparticle tracking analysis, transmission electron microscopy, flow cytometry, and tetraspanin expression. Cell lysates and isolated EVs were analyzed using liquid chromatography coupled with mass spectrometry, followed by Gene Set Enrichment Analysis to identify the altered pathways. KEY FINDINGS: Proteomic analysis of endothelial cells revealed that IS causes an increase in proteins related to adipogenesis, inflammation, and xenobiotic metabolism and a decrease in proliferation. Extracellular matrix elements, as well as proteins associated with myogenesis, response to UV irradiation, and inflammation, were found to be downregulated in IS-treated EVs. Fatty acid metabolism was also found to be increased along with adipogenesis and inflammation observed in cells. SIGNIFICANCE: The treatment of endothelial cells with IS increased the expression of proteins related to adipogenesis, inflammation, and xenobiotic metabolism and was less associated with proliferation. Furthermore, EVs from cells treated with IS may mediate endothelial dysfunction, since they present fewer extracellular matrix elements, myogenesis, inflammatory factors, and proteins downregulated in response to UV radiation.

Role of angiotensin II in cellular entry and replication of dengue virus.

Previous studies have demonstrated the relevance of several soluble molecules in the pathogenesis of dengue. In this regard, a possible role for angiotensin II (Ang II) in the pathophysiology of dengue has been suggested by the observation of a blockade of Ang II in patients with dengue, increased expression of molecules related to Ang II production in the plasma of dengue patients, increased expression of circulating cytokines and soluble molecules related to the action of Ang II, and an apparent relationship between DENV, Ang II effects, and miRNAs. In addition, in ex vivo experiments, the blockade of Ang II AT1 receptor and ACE-1 (angiotensin converting enzyme 1), both of which are involved in Ang II production and its function, inhibits infection of macrophages by DENV, suggesting a role of Ang II in viral entry or in intracellular viral replication of the virus. Here, we discuss the possible mechanisms of Ang II in the entry and replication of DENV. Ang II has the functions of increasing the expression of DENV entry receptors, creation of clathrin-coated vesicles, and increasing phagocytosis, all of which are involved in DENV entry. This hormone also modulates the expression of the Rab5 and Rab7 proteins, which are important in the endosomal processing of DENV during viral replication. This review summarizes the data related to the possible involvement of Ang II in the entry of DENV into cells and its replication.

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.

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.

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.

Breast Cancer: Metastasis, Molecular Subtypes, and Overweight and Obesity in Veracruz, Mexico.

INTRODUCTION: We assessed the association between overweight, obesity, and morbid obesity with the incidence of the most aggressive breast cancer subtypes in women. METHODS AND MATERIALS: A cross-sectional study was performed. We conducted a record review to identify the following aspects: body mass index, sociodemographic features, tumor characteristics, and reproductive and molecular aspects. Descriptive statistics and univariate analysis were performed to identify the association between the molecular subtypes and the study variables. In addition, we used multivariate analysis to identify the association between obesity and the presence of metastatic lymph nodes. RESULTS: We included 1446 women with an average age of 52.5 ± 12.1 years. Of the 1446 patients, 47% were premenopausal and 75% were overweight. Univariate analysis indicated a statistically significant association between obesity and advanced disease stage, as well as nulliparity and multiparity. Similar results were found for women with morbid obesity. Model 1 of the multivariate analysis showed an association between the presence of metastatic lymph nodes and obesity (odds ratio [OR], 1.6; P = .008) and histologic grade 2 or 3 (OR, 2.4; P = .003). Using model 2, an association was identified between an advanced disease stage and 2 factors: morbid obesity (OR, 1.9; P = .02) and positive human epidermal growth factor receptor 2 (OR, 1.8; P = .045). CONCLUSION: We found that obesity is associated with the more advanced stages of breast cancer. Further studies are needed to evaluate the role of obesity in breast cancer progression in women.

Cardiac myofibroblast induces decreased expression of major histocompatibility complex class II (Ia) on rat monocyte/macrophages.

The up-regulation of HLA antigens is important during heart inflammatory events and myofibroblasts may modulate the expression of this molecule in tissues. To test this possibility, the effect of cardiac myofibroblast:macrophage contact and the production of myofibroblast inhibitor factor(s) on the macrophage HLA (Ia) expression were studied. Listeria monocytogenes-elicited Ia + peritoneal macrophages (high Ia expression) were co-cultured with cardiac myofibroblasts for 3 and 7 days (myofibroblast contact). Proteosa peptone-elicited macrophages (low Ia expression) were cultured for 3 days with interferon gamma (INF-γ) and myofibroblast conditioned medium (FCM). Ia expression was analyzed by immunofluorescence and by radioimmune assay. Myofibroblast contact induced decreased expression of Ia molecule on macrophages (p < 0.001). This was confirmed by the radioimmune analysis in macrophage: myofibroblast co-cultures (p < 0.001). Double staining for Ia and CD14 showed that only CD14 positive cells (macrophages) expressed Ia molecule. FCM was capable of diminishing Ia expression induced by INF-γ on macrophages (p < 0.001). Decreased Ia macrophage expression induced by myofibroblasts could be important in the heart inflammation's resolution, probably involving Ia redistribution on cell: cell contact and myofibroblast inhibitor factor production.

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.

Losartan and enalapril decrease viral absorption and interleukin 1 beta production by macrophages in an experimental dengue virus infection.

The role of angiotensin II (Ang II) in dengue virus infection remains unknown. The aim of this study was to determine the effect of losartan, an antagonist of the angiotensin II type 1 receptor (AT1 receptor), and enalapril, an inhibitor of angiotensin I-converting enzyme (ACE), on viral antigen expression and IL-1ß production in peritoneal macrophages infected with dengue virus type 2. Mice treated with losartan or enalapril and untreated controls were infected intraperitoneally with the virus, and macrophages were analyzed. Infection resulted in increased IL-1ß production and a high percentage of cells expressing viral antigen, and this was decreased by treatment with anti-Ang II drugs, suggesting a role for Ang II in dengue virus infection.

Role of angiotensin II in experimental Venezuelan equine encephalitis in rats.

Venezuelan equine encephalitis (VEE) is a viral disease transmitted by mosquitoes. The inflammation induced by the VEE virus is associated with a high mortality rate in mice. Angiotensin II (Ang II), a pro-inflammatory molecule, is produced in the normal rat brain. There is no information about the role of this molecule in the inflammatory events occurring during VEE and the effect of inflammation on the mortality rate in VEE-virus-infected rats. This study was designed to determine the role of Ang II in VEE and to analyze the effect of inflammation on mortality in infected rats. Two groups of rats were studied: 1) Virus-infected animals and controls (n = 60) were treated with losartan (a blocker of the Ang II-AT1 receptor) or with pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) or left untreated and analyzed for morbidity and mortality. 2) Animals treated using the same protocol (n = 30) were sacrificed at day 4 postinfection and analyzed by immunohistochemistry and histopathology and for cytokine production. Increased expression of Ang II, ICAM-1, ED-1 and cytokines (IL-1α, MCP-1, IL-6 and IL-10) in infected animals was observed. The main histopathology findings were dilated capillaries and capillaries with endothelial detachment. Losartan and PDTC reduced the expression of IL-1α, MCP-1, and IL-10, and the number of dilated capillaries and capillaries with endothelial detachment. Survival analysis showed that 100% mortality was reached earlier in infected rats treated with losartan (day 14) or PDTC (day 11) than in untreated animals (day 19). These findings suggest that Ang II plays a role in VEE and that brain inflammation is protective against viral infection.

Ultrastructural Changes of Caudate Nucleus in Mice Chronically Treated with Manganese.

Manganese (Mn) is able to cross the blood-brain barrier and induces functional and structural alterations during the intoxication by this metal. Therefore, the effects of chronic administration of Mn in the caudate nucleus of mice were evaluated by electron microscopy. Male albino mice were injected intraperitoneally with MnCl2 (5 mg/kg/d) 5 d per week during 9 weeks. The control group received only 0.9% of NaCl solution. The caudate nuclei were extracted and subsequently processed to be observed on a conventional transmission electron microscope at 2, 4, 6, and 9 weeks after treatment. A high percentage of vacuolated and swollen mitochondria were found throughout all the analyzed periods. Myelin disarrangement and ultrastructural alterations related to edema were observed increased in Mn-treated mice at week 9. Granular degeneration of myelin at week 9 accompanied with deposition of electron dense granules in the neuropil was also observed. Edema in neuropil and glial cells was detected from week 2 to week 9 accompanied by swollen mitochondria. Neuronal bodies, synaptic terminals, and perivascular cells were found swollen. Decreased electron density in postsynaptic areas and decreased and dispersed synaptic vesicles in presynaptic areas were noted in Mn-treated animals. Some neurons from Mn-treated mice showed cisternae dilation of the Golgi apparatus. These results suggest that Mn-treatment produces structural alterations in the caudate nucleus that could be responsible for some of the neurotoxic effects of this metal.

Pro-inflammatory role of angiotensin II in mercuric chloride-induced nephropathy in rats.

Mercuric chloride (HgCl2), which induces kidney toxicity, constitutes a potential threat to human health. In addition to direct toxic effects, kidney inflammatory events take place during the HgCl2-induced nephropathy. There is no information currently available about the role of angiotensin II (Ang II) in this inflammatory process. Accordingly, the aim of this study was to determine the expression of Ang II and Ang II-associated inflammatory molecules, i.e. intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS), and mono-cyte/macrophage infiltration (ED-1), in HgCl2-induced nephropathy. Three groups of Sprague Dawley rats that were to receive HgCl2 (2.5 mg HgCl2/kg BW, by gavage) were utilized: one had received Losartan at 30 mg/kg BW; one had received Enalapril at 30 mg/kg BW; and one had received distilled water, in each case daily for 3 days prior to the HgCl2 exposure. For these studies, an extra set of controls treated with saline solution in place of HgCl2 and water in place of the test drugs was employed. Renal biopsies were obtained 96 h after HgCl2 injection and the expressions of Ang II, ICAM-1, iNOS, and ED-1 were analyzed by indirect immunoflourescence while tubular damage was assessed via histopathology. An increased expression of Ang II, ICAM-1, iNOS, and ED-1 as well as increases in tubular necrosis were observed in all HgCl2-animals. Treatments with Losartan or Enalapril diminished the induced expressions as well as the extent of tubular damage. The data here suggest that Ang II is involved in the pro-inflammatory events during HgCl2-induced nephropathy, and that this is probably mediated, in part, by Ang II receptors Type 1 (AT-1).

Role of angiotensin II in the brain inflammatory events during experimental diabetes in rats.

Hyperglycemia during diabetes is one of the causes of encephalopathy. However, diabetes causes chronic inflammatory complications and among them is peripheral neuropathy. Since, diabetes is one of the major risk factors for cerebrovascular disease, inflammatory process could take place in central nervous system (CNS). To test that hypothesis, experiments to determine inflammatory events in CNS during streptozotocin-induced diabetes were performed. Diabetes was induced by intravenous injection of streptozotocin (STZ). Brain angiotensin II (Ang II), monocyte/macrophage (ED-1 positive cells), CD8, the intercellular adhesion molecule-1 (ICAM-1), the lymphocyte function-associated antigen-1 (LFA-1) and superoxide anion were determined by hystochemical and immunohistochemical methods. Nitric oxide (NO), malondialdehyde (MDA) and catalase activity were measured in brain homogenates by enzymatic and biochemical methods. This research showed increased expressions of Ang II, ICAM-1, LFA-1 and CD8 positive cells in diverse zones of cerebrum and cerebellum of diabetic rats (week 8). Treatment of diabetic animals with losartan or enalapril reduced the expression of those molecules. Values of lipid peroxidation, nitrite content and superoxide anion expression remained similar to control rats. Only decreased activity of catalase was observed in diabetic animals, but losartan or enalapril failed to modify catalase activity. This study suggests the presence of Ang II-mediated brain inflammatory events in diabetes probably mediated by AT1 receptors.

Proinflammatory role of angiotensin II in a rat nephrosis model induced by adriamycin.

INTRODUCTION: Nephrotic syndrome induced by adriamycin (ADR) is an experimental model of glomerulosclerosis in humans. The AT(1) receptor for angiotensin II (Ang II) is involved in the renal expression of the nuclear factor-kappa B (NF-ΚB) during this nephrosis. NF-ΚB is a transcription factor for proinflammatory effects of Ang II; however, there is no information about the role of this receptor in the renal proinflammatory events in ADR nephrosis. MATERIALS AND METHODS: To determine the role of Ang II in ADR nephrosis, Sprague-Dawley rats were treated with ADR (6 mg/kg iv). One ADR group received oral losartan treatment (15 mg/kg gavage) 3 days before ADR injection and then daily for 4 weeks, and the other group water. Animals were sacrificed at week 4 and renal macrophage infiltration, ICAM-1, superoxide anion (O(2(-))) and Ang II expressions were analysed by indirect immunofluorescence and histochemical techniques. RESULTS: ADR rats showed increased expression of ICAM-1, Ang II, O(2(-)) and macrophage infiltration, events that were diminished by losartan treatment. Ang II expression remained unaltered after antagonist treatment. Proteinuria was reduced after 3 weeks of treatment. CONCLUSIONS: These data suggest that Ang II plays a role in the inflammatory events during ADR-induced nephrosis, probably mediated by AT(1) receptors.

Variability of hair coat and skin traits as related to adaptation in Criollo Limonero cattle.

The variation in hair coat and skin histology traits of Criollo Limonero cattle was analyzed using 213 Criollo Limonero females. Skin biopsies were obtained from slick-haired (N=16) and normal-haired (N=14) animals. Measured traits included hair length (HL), color coat (CC), number of hair follicles per square centimeter (NHF), sweat glands per square centimeter (NSG), sweat glands size (SGS), sebaceous glands per square centimeter (NSBG), blood vessels per square centimeter (NBV), and thickness of epidermis (TE). Hair length differed (P<0.001) between slick- and normal-haired animals (4.9 ± 0.12 vs 10.9 ± 0.20, respectively). Differences (P<0.01) in CC (Bayo = 144/67.6% vs Red = 69/32.4%) and HL (slick-haired = 199/93.4% vs normal-haired = 14/6.5%) were found. Distribution of slick- and normal-haired animals differed (P<0.01) between bayo-coated and red-coated (139/62.2% vs 9/4.2%; respectively). Most (P<0.05) red-coated animals belonged to a single family. No differences (P>0.05) were found between slick-haired and normal-haired animals in NHF (637 ± 164 vs 587 ± 144, respectively), NSG (556 ± 134 vs 481 ± 118, respectively), NSBG (408 ± 87 vs 366 ± 77, respectively), NBV (1628 ± 393 vs 1541 ± 346, respectively), and TE (1.24 ± 0.14 vs 1.32 ± 0.12, respectively). However, SGS was greater (P<0.01) in slick-haired than normal-haired animals. In conclusion, Criollo Limonero cattle are predominantly bayo-coated, slick-haired, with a reduced number of hair follicles relative to Zebu cattle, sweat and sebaceous glands in proportion to hair follicle numbers, and with a high blood flow irrigating the skin. There is a sub-group of red-coated animals with yellow or cream skin, thicker epidermis, and with a higher frequency of normal-haired animals. It appears that the slick hair gene has been favored by natural selection in this breed.

Ultrastructural study of the hypothalamus in mice chronically treated with manganese / Estudio ultraestructural del hipotálamo de ratones tratados crónicamente con manganeso

Manganese (Mn) is an essential metal that is an integral part of some metalloproteins and acts as a cofactor of several enzymes. Mn is able to cross the blood-brain barrier and enter the nervous system. It has a low toxicity but exposure to high concentrations or for prolonged periods of time produce neurological disorders in humans that initially cause hallucinations and compulsive behaviour followed by stiffness, muscle weakness, ataxia, memory loss and a tremor resembling Parkinson’s disease. This study assessed the ultrastructural alterations produced in the hypothalamus of male albino mice injected intraperitoneally with MnCl2 (5 mg Mn/Kg/day) and a control group injected with NaCl 0.9% (0.1 mL) daily for 9 weeks. The animals were sacrificed by cervical dislocation. The hypothalamus was extracted and subsequently processed to be observed on the conventional transmission electron microscope at 2, 4, 6 and 9 weeks of treatment. After 2 weeks it was observed a slight disruption of the Golgi apparatus and the myelin fibers. After 4 weeks the disorganization was accentuated and dilatation of the endoplasmic reticulum (ER) and alterations of mitochondria were observed. After 6 weeks the normal pattern of the myelin sheath was lost. After 9 weeks of treatment it was found swollen mitochondria with lost of crystae, a marked dilatation of rough and smooth endoplasmic reticulum and dendrites with a high degree of swelling. These results suggest that the neurotoxic effect of Mn increases as time of exposure passes and produces ultrastructural alterations of nerve cells in the hypothalamus.

El manganeso (Mn) es un metal esencial que forma parte de algunas metaloproteínas y actúa como cofactor de varias enzimas. El Mn es capaz de atravesar la barrera hematoencefálica e ingresar al sistema nervioso. Presenta baja toxicidad, pero la exposición a altas concentraciones o por tiempos prolongados produce alteraciones neurológicas en humanos que inicialmente provocan alucinaciones y conducta compulsiva seguidas por rigidez, debilidad muscular, ataxia, pérdida de la memoria y temblor, síntomas similares a los de la enfermedad de Parkinson. En el presente estudio se evaluaron los efectos tóxicos del Mn sobre la ultraestructura del hipotálamo de ratones. Se inyectaron intraperitonealmente ratones albinos machos con MnCl2 (5 mg Mn/Kg/día durante 9 semanas). El grupo control recibió NaCl 0,9% (0,1 mL/dosis). Los animales se sacrificaron por dislocación cervical, extrayéndose y disecándose el hipotálamo, que posteriormente se procesó para realizar observaciones al microscopio electrónico de transmisión convencional a las 2; 4; 6 y 9 semanas de tratamiento. A las 2 semanas, se observó ligera desorganización en el aparato de Golgi y en las fibras mielínicas. A las 4 semanas, se acentuó la desorganización y se comenzó a observar dilatación del retículo endoplasmático liso y rugoso asi como mitocondrias alteradas. A las 6 semanas, se encontró pérdida del patrón normal de la cubierta mielínica. Finalizadas las 9 semanas de tratamiento, se observaron mitocondrias hinchadas con pérdida de las crestas, dilatación acentuada del retículo endoplasmático rugoso y liso y dendritas con cierto grado de edema. Estos resultados parecen indicar que el efecto neurotóxico del Mn aumenta a medida que transcurre el tiempo de exposición para producir alteraciones ultraestructurales de las células nerviosas del hipotálamo.

Structural and ultrastructural analysis of cerebral cortex, cerebellum, and hypothalamus from diabetic rats.

Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral.

Efecto del consumo de cultivo de levaduras Saccharomyces cerevisiae y/o selenio en pollos de engorde expuestos a bajos niveles de aflatoxina B1 en la dieta: 2: morfología hepática / Effect of Saccharomyces cerevisiae culture and/or selenium intake on broiler exposed to low levels of aflatoxin B1 in the ration: 2: hepatic morphology

El presente estudio fue conducido para determinar el efecto de 0,1 por ciento de cultivo de levaduras Saccharomyces cerevisiae 1026 (Sc)y/o 2mg/kg de selenio (Se) en el alimento contaminado con 0,07mg/kg (70 ppb) de aflatoxina B1 (AFB1 ), sobre la morfología hepática de pollos de engorde. Un total de 480 pollos Hubbar x Hubbar, machos, de un día de nacidos, fueron asignados al azar para recibir 8 tipos de dietas durante 42 días, cada una con 4 replicas de 15 pollos, estas correspondieron a los siguientes tratamientos (T) T1 : grupo control que consiste en alimento comercial (AC) sin niveles detectables de aflatoxina; T2: AC + AFB1; T3: AC + Sc; T4: AC + AFB1 + Sc; T5: AC + Se; T6: AC + AFB1 + Se; T7: AC + Sc + Se; T8: AC + AFB1 + Sc + Se. La ingestión de Sc y/o Se en el alimento sin o con AFB1 , no causaron lesiones macroscópicas en los hígados. Se observó un incremento (P<0,05) del peso relativo del hígado en el T4 comparado con el T1 y T3 y en los pollos del T5 y T6 (P<0,01) con relación al T 1. Los T con Sc y/o Se en el alimento sin y con AFB1 , presentaron una significativa frecuencia de lesiones hepatotóxicas con respecto al T 1, sin embargo la combinación de Sc + Seen el alimento con AFB1 (T8), disminuyó el grado de severidad de las lesiones hepatotóxicas, en comparación al grado de hepatotoxicidad de las aves que recibieron estos aditivos por separado (T4 y T6). Estos resultados indican un aparente sinergismo de ambos aditivos para disminuir la hepatotoxicidad causada por la ingestión de alimento con AFB1.

This trial was undertaken to determine the effects of 0.1% the yeast culture Saceharonyces cerevisiae1026 (Sc) and/or 2mg/kg of selenium (Se) added to contaminated foodstuff with 0,07mg/kg (70 ppb) of aflatoxin B1 (AFB1), on hepatic morphology of broiler chickens. 480 1-day-old male Hubbar x Hubbar chickens were chosen randomly to receive 8 sorts of diets for 42 days, each diet with 4 replicates of 15 chickens. Those diets corresponded to the fallowing treatments (T): T1: control group receiving commercial food (CF) without detectable aflatoxin levels; T2: CF + AFB1; T3: CF + Sc; T4: CF + AFB1 + Sc; T5: CF + Se; T6: CF +AFB1 + Se; T7: CF + Sc + Se; T8: CF + AFB1 + Sc + Se. Neither Sc or Se added to foodstuff alone or in combination with or without AFB1, caused macroscopic lesions in liver. A relative liver weight increase was observed in T4 compared with T1 and T3 (P<0.05) and in chickens from T5 and T6 (P<0.01) compared with T1. Treatments with Sc and/or Se were shown to have a significative higher frequency of hepatotoxic lesions compared with that of T1. However, Sc + Se added together to AFB1 contaminated food (T8) diminished the hepatotoxic lesions’ severity grading compared to the hepatotoxcity grade found in T4 and T6. This result indicates an apparent synergistic effect of both additives as for diminishing hepatotoxicity caused by AFB1-contaminated foodstuff Ingestion.