International journal of physiology, pathophysiology and pharmacology最新文献

A growing body of studies has demonstrated that acute transcranial magnetic stimulation (TMS) therapy for treatment-resistant major depressive disorder (MDD) has achieved significant antidepressant effects and can alleviate other related symptoms. However, MDD has a high relapse rate, and patients with depressive symptoms can relapse weeks or months after acute TMS treatment. The lack of necessary TMS maintenance protocols after completing acute TMS treatment with full remission might be one of the reasons for the high relapse rates in MDD patients. Thus, investigating post-TMS treatment maintenance guidelines is important for decreasing relapse in treatment-resistant depression patients who had initially responded to acute TMS therapy. Therefore, we recommend a scientific approach to decrease relapse in treatment-resistant depression patients who had initially responded to acute TMS treatment.

Background & objectives: Hypertension can be induced by inhibiting nitric oxide synthesis with L-NAME, which also has a role in oxidative stress. Curcumin has strong antioxidant property. Our aim was to examine the possible preventive role of curcumin on renal dysfunction secondary to hypertension.

Material & methods: Twenty-four adult male Albino rats were divided in four groups: normal (N); curcumin (C; received curcumin 100 mg/kg/day by oral gavage for 10 weeks); hypertensive (H; received L-NAME 40 mg/kg/day in their drinking water for 4 weeks); and hypertensive-curcumin (HC; received L-NAME and curcumin). Arterial blood pressure was evaluated non-invasively for 4 weeks. Rats were then sacrificed for assessment of oxidative stress (catalase, lipid peroxidase, reduced glutathione and superoxide dismutase), renal function and structure, and biomarkers of apoptosis (Bcl-2 and caspase-3). AT1R expression and renal mtDNA integrity were also assessed.

Results: Curcumin attenuated the effects of L-NAME on blood pressure and renal function. The renal histopathological changes observed in the L-NAME group were improved by curcumin administration. The expression of Bcl2 and caspase-3 was improved associated with downregulation of AT1R in curcumin treated groups. The antioxidant markers and mtDNA fragmentation show marked increase in hypertensive group which significantly decreased after curcumin treatment.

Conclusion: Curcumin improved blood pressure elevation renal dysfunction. These improvements mediated through anti-oxidant capabilities and downregulation of AT1R favoring reduced apoptosis and preserved mitochondrial DNA.

Acute ischemic stroke (AIS) is the 5^th leading cause of death and the leading cause of neurological disability in the United States. The oxygen and glucose deprivation associated with AIS not only leads to neuronal cell death, but also increases the inflammatory response, therefore decreasing the functional outcome of the brain. The only pharmacological intervention approved by the US Federal Food and Drug Administration for treatment of AIS is tissue plasminogen activator (t-PA), however, such treatment can only be given within 4.5 hours of the onset of stroke-like symptoms. This narrow time-range limits its therapeutic application. Administrating t-PA outside of the therapeutic window may induce detrimental rather than beneficial effects to stroke patients. In order to reduce the infarct volume of an AIS while increasing the time period for treatment, new treatments are essential. Emerging monoclonal antibody (mAb) therapies reveal great potential by targeting signaling pathways activated after an AIS. With successful application of mAb in the treatment of cancer, other therapeutic uses for mAb are currently being evaluated. In this review, we will focus on recent advances on AIS therapy by using mAb that targets the signaling cascades and endogenous molecules such as inflammation, growth factors, acid-sensing ion channels, and N-methyl-D-aspartate receptors. Therefore, developing specific mAb to target the signaling pathways of ischemic brain injury will benefit patients being treated for an AIS.

Hibiscus sabdariffa (HS) is native to tropical and subtropical regions, and its enrichment as a source of antioxidants and phytoestrogen has been documented. The present study investigated effects of HS on ovarian toxicity induced by cadmium. Adult female Wistar rats were grouped into 4 (n=5/group): Group A received HS (100 mg/kg), group B received cadmium sulphate (5 mg/kg), group C received cadmium sulphate and HS, and group D (control) received 1 ml of distilled water. Cadmium sulphate was administered for five days (i.p) followed by oral administration of HS for 28 days. Results showed distortion in the cytoarchitecture of the follicular cells in the ovary of cadmium-treated rats while there was mild or no distortion recorded for the ovary of the rats treated with cadmium and HS. There was also a significant reduction in the serum level of Luteinizing and follicle stimulating hormone of the rats treated with cadmium (group B) when compared with control rats. However, these alterations were attenuated when treated with HS. We concluded that HS has an ovarian protective effect in cadmium-treated adult female rats. Hence the present results suggest that HS extract would be a potential therapeutic agent in ovarian dysfunction.

Nutrigenomic malnutrition during pregnancy and early postnatal life has serious consequences on original organ-programing, growth pattern, puberty and quality of life. The aim of this was to investigate the effect of two notable flavonoids, quercetin and kaempferol, with nutrigenomic potentials on prenatal and early postnatal food restrictions or both on gestational outcomes and the onset of puberty in male and females Wister rats. In three sets of experiments consisting of prenatal, postnatal food deprivations or both, rats were distributed into various treatment groups (n = 6). Prenatal food restriction (PrNFR) was initiated by 50% of ad libitum available diet in pregnancy (days 1-22) simultaneously with quercetin (50, 100 and 200 mg/kg, p.o./day) or kaempferol (50, 100 and 200 mg/kg, p.o./day) until delivery. However, postnatal food restriction (PsNFR) was simulated by litter-increment to 16 pups per mother from postnatal day 2 together with quercetin (50-200 mg/kg, p.o.) or kaempferol (50-200 mg/kg, p.o.) treatments until weaning (day 24) respectively. The last experiment encompasses both protocols with similar treatment protocols. Kaempferol attenuated PrNFR-induced alterations in gestational length compared to PrNFR-control. Quercetin and kaempferol significantly (P < 0.05) normalized nose-length of pups of rats exposed to PrNFR. Quercetin and kaempferol reduced the number of stillbirths due to PrNFR. Both also reduced the delay in pubertal onset as evidenced by normal onset of balanopreputial-separation and vaginal-opening in the PrNFR, PsNFR and PrNFR-PsNFR male and female rats respectively. Together, quercetin and kaempferol prevents prenatal and postnatal malnutrition-induced altered gestational outcomes and pubertal delays in rats.

In this study, we investigated the effect of hypoxia and concomitant sildenafil treatment on MHC isoforms in hypoxia-induced hypertrophied right ventricles. Right ventricular hypertrophy was induced in mice by exposing them to hypoxic stimulus (11% ambient oxygen) in a normobaric chamber for 20 days. 45 mice were used in this study, distributed randomly into three groups: the first group served as a control (CO), the second group was exposed to hypoxia for 20 days without sildenafil treatment (HY), and the third group was given sildenafil orally at a dose of 30 mg.kg^-1.day^-1 plus exposure to hypoxia for 20 days (HS). Relative amounts of MHC isoforms were calculated using two ELISA kits containing antibodies against α and β MHC, and by SDS-PAGE. Compared with the CO group, the HY group showed a significant increase in right ventricle weight/left ventricle plus septum ratio (Fulton's ratio). The HS group showed a significant decrease in Fulton's ratio compared with the HY group, but not with the CO group. Expression of the MHC-β isoform was significantly increased in the HY group compared with the CO group. There was no significant difference in MHC-β between the HY group and the HS group. Plasma atrial natriuretic peptide level was significantly higher in HY group than HS group and did not return to normal after sildenafil treatment. Conclusion: sildenafil reversed the right ventricular hypertrophy induced by hypoxia but did not decrease the expression of MHC-β to normal levels.

Introduction: Multiple Sclerosis (MS) is a chronic neurological disorder with no known cause or cure. Fingolimod (FTY720) is an oral medication recently approved for the treatment of MS as well as other diseases with autoimmune aspects. However, the drug is not without side effects. The severity and prevalence of these side effects are not completely understood. One of the most common causes for the patient cessation of fingolimod is an increase in liver enzymes, indicating possible inflammation or damage to liver cells. Alanine transaminase (ALT) and aspartate transaminase (AST) are the most common liver enzymes used as indicators of hepatic health.

Objectives: This three-month prospective cohort study selected patients who were diagnosed with relapsing-remitting MS (RRMS) and who were not taking fingolimod oral treatment. ALT and AST levels were determined for these patients at baseline and then after three months of taking FTY720 to determine if these liver enzymes were changed.

Methods: 36 RRMS patients completed this study, which lasted three months. They were started on 0.5 oral FTY720 after approval from a physician and completion of an AST/ALT blood test. Baseline levels were determined and then taken again three months later. Statistical analysis of these values was performed using P<0.05 as a significance threshold.

Results: In this sample of patients, only ALT levels were significantly increased after fingolimod treatment in the general cohort (P=0.00). The general cohort showed an insignificant increase in AST levels. In male and female populations separately, AST was not significantly increased. ALT was only significantly increased in men (P=0.00) and insignificantly increased in women.

Conclusion: This study further confirms our concerns about fingolimod's possible effects on the liver. While these numbers do support the claim that the drug does on average increase ALT in patient populations, it is important to note that most of these patients have no real hepatic side effects. In addition, previous studies have cited a return to normal ALT and AST levels after cessation of fingolimod, suggesting its effects are temporary and not severely damaged in the usual patient.

Tight junctions are important structures that form the barrier of cells and tissues, and they play key roles in maintaining homeostasis of our body. The backbone of the tight junction proteins are claudins, which composed more than twenty members. The tight junction protein 1 (TJP1), also called ZO-1 (Zonula Occludens-1), is one of the tight junction related proteins, and it is widely used in literature to label tight junctions. Here we showed that TJP1 (ZO-1) is highly expressed in cancerous HeLa cells, fibroblast cells, HUVEC as well as MDCK cells, while claudin-1 is highly expressed in HUVEC and MDCK cells, but not expressed in HeLa and fibroblast cells. We aimed to investigate whether tight junction is present in HeLa and fibroblast cells. We used transepithelial/transendothelial electrical resistance (TEER) to measure tight junction dynamics in these cells. The results showed that there is no TEERs in HeLa and fibroblast cells, while there is relatively high TEER in HUVEC and MDCK cells. Importantly, the TEER in MDCK cells is dramatically reduced after knockdown of TJP1 (ZO-1). These results suggest that TJP1 (ZO-1) cannot be used as a marker of tight junctions in a variety of cells, while TJP1 (ZO-1) may play an important role in regulation of tight junctions in MDCK cells.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS). Although the exact etiology of multiple sclerosis is unknown, researchers suggest that genetic, environmental, and microbial factors play a central role in causing multiple sclerosis. Pathology of multiple sclerosis is based on inflammation as T cells enter the brain via disruptions in the blood-brain barrier, recognizing myelin as foreign antigen; and as a result, the T cells attack myelin and start the inflammatory processes, enhancing inflammatory cytokines and antibodies. Since previous studies show ethanol can suppress the immune system such as innate, humoral, and cellular immunity and increases the production of anti-inflammatory cytokines, we hypothesized maybe ethanol also have ameliorating effects on multiple sclerosis symptoms. Although alcohol induces apoptosis in oligodendrocytes and neurons, causing demyelination and affects CNS directly, in this study we will investigate ethanol's effects on some aspects of the immune system in multiple sclerosis.

Background: Lung Protective Ventilation (LPV) refers to a combination of measures aimed at reducing ventilator-associated lung injury. This includes: delivering tidal volumes of 6-8 ml/kg of ideal body weight, use of positive end expiratory pressure and recruitment maneuvers. With Postoperative Pulmonary Complications (PPCs) contributing towards significant morbidity and mortality following surgery, evidence indicates that effective use of LPV measures intraoperatively has been associated with reduced rates of PPCs.

Methods: We conducted a post-hoc analysis using data from a recent clinical audit on departmental ventilation practices. Potential risk factors for excessive tidal volume ventilation were assessed using univariable and multivariable regression models.

Results: Obesity and gender are independently associated with risk of excessive ventilation. In contrast, the urgency and length of surgery, the choice of airway devices and the mode of ventilation were not associated with excessive ventilation.

Conclusion: There is an association between female gender, obesity and excessive tidal volume ventilation. This may be addressed through formal, protocolized intraoperative ventilation setting.