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 alpha and beta cells after 6 months of treatment. Moreover, we assessed by stereological methods, the mean volume of islets (Vi) and three important variables: the fractional beta -cell area, the cross-sectional area of alpha (A alpha-cell) and beta cells (A beta-cell), and the number of beta and alpha 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 beta cell area (78.2±30.9; p<0.05) compared to W. Accordingly, a reduced mean value of islet alpha and beta 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 beta-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.
Exercise performance and zinc administration individually yield a protective effect on various neurodegenerative models, including ischemic brain injury. Therefore, this work was aimed at evaluating ...the combined effect of subacute prophylactic zinc administration and swimming exercise in a transient cerebral ischemia model. The prophylactic zinc administration (2.5 mg/kg of body weight) was provided every 24 h for four days before a 30 min common carotid artery occlusion (CCAO), and 24 h after reperfusion, the rats were subjected to swimming exercise in the Morris Water Maze (MWM). Learning was evaluated daily for five days, and memory on day 12 postreperfusion; anxiety or depression-like behavior was measured by the elevated plus maze and the motor activity by open-field test. Nitrites, lipid peroxidation, and the activity of superoxide dismutase (SOD) and catalase (CAT) were assessed in the temporoparietal cortex and hippocampus. The three nitric oxide (NO) synthase isoforms, chemokines, and their receptor levels were measured by ELISA. Nissl staining evaluated hippocampus cytoarchitecture and Iba-1 immunohistochemistry activated the microglia. Swimming exercise alone could not prevent ischemic damage but, combined with prophylactic zinc administration, reversed the cognitive deficit, decreased NOS and chemokine levels, prevented tissue damage, and increased Iba-1 (+) cell number. These results suggest that the subacute prophylactic zinc administration combined with swimming exercise, but not the individual treatment, prevents the ischemic damage on day 12 postreperfusion in the transient ischemia model.
In the cerebral hypoxia-ischemia rat model, the prophylactic administration of zinc can cause either cytotoxicity or preconditioning effect, whereas the therapeutic administration of selenium ...decreases the ischemic damage. Herein, we aimed to explore whether supplementation of low doses of prophylactic zinc and therapeutic selenium could protect from a transient hypoxic-ischemic event. We administrated zinc (0.2 mg/kg of body weight; ip) daily for 14 days before a 10 min common carotid artery occlusion (CCAO). After CCAO, we administrated sodium selenite (6 μg/kg of body weight; ip) daily for 7 days. In the temporoparietal cerebral cortex, we determined nitrites by the Griess method and lipid peroxidation by the Gerard-Monnier assay. qPCR was used to measure mRNA of nitric oxide synthases, antioxidant enzymes, chemokines, and their receptors. We measured the enzymatic activity of SOD and GPx and protein levels of chemokines and their receptors by ELISA. We evaluated long-term memory using the Morris-Water maze test. Our results showed that prophylactic administration of zinc caused a preconditioning effect, decreasing nitrosative/oxidative stress and increasing GPx and SOD expression and activity, as well as eNOS expression. The therapeutic administration of selenium maintained this preconditioning effect up to the late phase of hypoxia-ischemia. Ccl2, Ccr2, Cxcl12, and Cxcr4 were upregulated, and long-term memory was improved. Pyknotic cells were decreased suggesting prevention of neuronal cell death. Our results show that the prophylactic zinc and therapeutic selenium administration induces effective neuroprotection in the early and late phases after CCAO.
Acute and subacute administration of zinc exert neuroprotective effects in hypoxia-ischemia animal models; yet the effect of chronic administration of zinc still remains unknown. We addressed this ...issue by injecting zinc at a tolerable dose (0.5 mg/kg weight, i.p.) for 14 days before common carotid artery occlusion (CCAO) in a rat. After CCAO, the level of zinc was measured by atomic absorption spectrophotometry, nitrites were determined by Griess method, lipoperoxidation was measured by Gerard-Monnier assay, and mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors was measured by qRT-PCR, whereas nitrotyrosine, chemokines, and their receptors were assessed by ELISA and histopathological changes in the temporoparietal cortex-hippocampus at different time points. Long-term memory was evaluated using Morris water maze. Following CCAO, a significant increase in nitrosative stress, inflammatory chemokines/receptors, and cell death was observed after 8 h, and a 2.5-fold increase in zinc levels was detected after 7 days. Although CXCL12 and FGF2 protein levels were significantly increased, the long-term memory was impaired 12 days after reperfusion in the Zn+CCAO group. Our data suggest that the chronic administration of zinc at tolerable doses causes nitrosative stress, toxic zinc accumulation, and neuroinflammation, which might account for the neuronal death and cerebral dysfunction after CCAO.
Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. ...Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.
Leflunomide, a disease-modifying antirheumatic drug, has been shown to be effective in the management of rheumatoid arthritis (RA). Among other side effects, systemic hypertension has been described, ...and also a case of possible pulmonary hypertension (PH) has been reported. Symptomatic PH in RA is rare. We present a 28-year-old woman with a history of RA who consulted our hospital because of severe symptomatic pulmonary hypertension. Two years before admission, she was started on leflunomide. Due to previous evidence of the association of leflunomide with pulmonary hypertension, the drug was stopped. The patient became asymptomatic with normal pulmonary arterial pressure within a year. Given the poor prognosis of idiopathic pulmonary arterial hypertension, the recognition of potentially reversible causes is crucial. Until further evidence is available in a patient who develops pulmonary arterial hypertension, stopping leflunomide should be considered.
The transient hypoxic-ischemic attack, also known as a minor stroke, can result in long-term neurological issues such as memory loss, depression, and anxiety due to an increase in nitrosative stress. ...The individual or combined administration of chronic prophylactic zinc and therapeutic selenium is known to reduce nitrosative stress in the first seven days post-reperfusion and, due to an antioxidant effect, prevent cell death. Besides, zinc or selenium, individually administered, also causes antidepressant and anxiolytic effects. Therefore, this work evaluated whether combining zinc and selenium could prevent stroke-elicited cognition and behavior deficits after 30 days post-reperfusion. Accordingly, we assessed the expression of growth factors at 7 days post-reperfusion, a four-time course of memory (from 7 to 28 days post-learning test), and cell proliferation, depression, and anxiety-like behavior at 30 days post-reperfusion. Male Wistar rats with a weight between 190 and 240 g) were treated with chronic prophylactic zinc administration with a concentration of 0.2 mg/kg for 15 days before common carotid artery occlusion (10 min) and then with therapeutic selenium (6 μg/kg) for 7 days post-reperfusion. Compared with individual administrations, the administration combined of prophylactic zinc and therapeutic selenium decreased astrogliosis, increased growth factor expression, and improved cell proliferation and survival in two regions, the hippocampus, and cerebral cortex. These effects prevented memory loss, depression, and anxiety-like behaviors. In conclusion, these results demonstrate that the prophylactic zinc administration combined with therapeutic selenium can reduce the long-term sequelae caused by the transient ischemic attack.
Significance statement.
A minor stroke caused by a transient ischemic attack can result in psychomotor sequelae that affect not only the living conditions of patients and their families but also the economy. The incidence of these micro-events among young people has increased in the world. Nonetheless, there is no deep understanding of how this population group responds to regular treatments (Ekker and et al., 2018) 1. On the basis that zinc and selenium have antioxidant, anti-inflammatory, and regenerative properties in stroke animal models, our work explored whether the chronic combined administration of prophylactic zinc and therapeutic selenium could prevent neurological sequelae in the long term in a stroke rat model of unilateral common carotid artery occlusion (CCAO) by 10-min. Our results showed that this combined treatment provided a long-term neuroprotective effect by decreasing astrogliosis, memory loss, anxiety, and depression-like behavior.
Brugada syndrome is characterized electrocardiographically by ST segment elevation in the right precordial leads, followed by a negative T wave unrelated to ischemia, electrolyte disturbance or drug ...effects and prone to rapid polymorphic ventricular tachycardia capable of degenerating into ventricular fibrillation. The ECG pattern may be dynamic and is often concealed. Sodium channel blockers, drugs, electrolyte imbalances, fever and several other clinical circumstances are recognized inducers of a Brugada type 1 ECG in susceptible patients. We describe a case of a Brugada type 1 ECG pattern induced by severe hyponatremia.
The aim of this study was to compare the outcome of 3 months vs. 18 months of amiodarone treatment after atrial fibrillation (AF) conversion in patients who experienced the first episode of ...persistent AF.
We included 51 patients who experienced the first episode of persistent AF receiving amiodarone (600 mg) daily for 4-6 weeks. If AF persisted, electrical cardioversion (ECV) was performed. All patients received amiodarone (200 mg daily) for 3 months and then were randomized to amiodarone (Group I) or placebo (Group II) and followed for 15 months. The control group comprised 9 untreated patients undergoing ECV. Treatment effectiveness was evaluated using a Bayesian model.
Eighteen months after AF reversion, 22 (81.5%) patients in Group I, 13 (54.2%) patients in Group II, and 1 (11.1%) patient in the control group remained in sinus rhythm. No differences were found between Group I patients who required ECV and Group II patients. Sinus rhythm was preserved in all Group I patients when it was achieved during amiodarone administration. Limiting adverse effects occurred in 3 (11.1%) patients in Group I.
In patients regaining sinus rhythm after the first episode of persistent AF, a 3-month amiodarone treatment after reversion is a reasonable option for rhythm control.
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