The Effects of Low and High Concentrations of Luteolin on Cultured Human Endothelial Cells Under Normal and Glucotoxic Conditions: Involvement of Integrin‐Linked Kinase and Cyclooxygenase‐2

Luteolin protects against high glucose (HG)‐induced endothelial dysfunction whereas its cytotoxicity has been reported against normal endothelial cells. This study was undertaken to determine luteolin cytoprotective and cytotoxic dose ranges and to elucidate their respective mechanisms. Luteolin prevented HG‐induced human umbilical vein endothelial cell (HUVEC) death with an EC50 value of 2.0 ± 0.07 μM. The protective effect of luteolin was associated with decreased intracellular reactive oxygen species (ROS) and Ca²⁺ (Cai²⁺) levels and enhanced nitric oxide (NO) production. At high concentrations, luteolin caused HUVEC death in normal glucose (NG) and HG states (LC₅₀ 40 ± 2.23 and 38 ± 1.12 μM, respectively), as represented by increased ROS and Cai²⁺ and decreased NO. Western blots illustrated that exposure to HG increased cyclooxygenase‐2 (COX‐2) and integrin‐linked kinase (ILK) expression. Luteolin at low concentrations suppressed HG‐mediated up‐regulation of COX‐2 but maintained HG‐induced over‐expression of ILK while at high concentrations significantly increased COX‐2 and decreased ILK expression in both HG and NG states. Our data indicated that cytoprotective action of luteolin was manifested with much lower concentrations, by a factor of approximately 20, compared with cytotoxic activity under both normal or glucotoxic conditions. It appears that luteolin exerts its action, in part, by modulating ILK expression which is associated with regulation of COX‐2 expression and NO production in endothelial cells. Copyright © 2014 John Wiley & Sons, Ltd.     

Local nasal immunotherapy and bronchial hyperreactivity in seasonal allergic rhinitis: an observational pilot study.

The clinical efficacy of local nasal immunotherapy (LNIT) in patients with allergic rhinitis is amply documented. The aim of the study was to determine the effect on bronchial hyperresponsiveness (BHR) assessed at baseline and after 3 years of LNIT or pharmacological treatment alone. Forty-three randomized patients with allergic oculorhinitis were enrolled (26 positive to Graminaceae and 17 to Parietaria judaica pollens). All patients were asked whether they were willing to follow a 3-year treatment course involving preseasonal LNIT with a powder extract of Graminaceae or Parietaria pollens. Twenty-four patients (16 allergic to Graminaceae and eight to Parietaria) selected LNIT and the other 19 opted for symptomatic pharmacological treatment only. The latter was considered the control group. On the basis of positive or negative bronchial hyperresponsiveness and the LNIT, four subgroups were established and followed in open conditions, during which a record was kept of symptom scores, drug use, spirometry and methacholine test findings. After 3 years, patients treated with LNIT had a significant reduction of symptoms and drug intake. In the controls, symptoms worsened, thus requiring more drugs to control them. Bronchial hyperresponsiveness significantly improved in hyperreactive patients receiving LN7IT 10 of whom were no longer hyperreactive and one at a higher threshold. Among controls, bronchial hyperresponsiveness did not change, with the exception of three nonreactive patients who became hyperreactive, one of them with asthma. These findings confirm the efficacy of LNIT in allergic rhinitis suggesting that it might have systemic activity interfering with bronchial hyperresponsiveness and hence the onset of bronchial asthma.     

Progress in heart transplantation.

The field of heart transplantation was built upon the discoveries of immunity and tolerance by Landsteiner, Medawar, Burnet, and others, as well as technical advancements in surgical technique by Carrel. Since the first successful human heart transplant performed by Christiaan Barnard in 1967, there has been substantial progress in the field of heart transplantation, especially over the last several decades. With advances in immunosuppression and surgical techniques, the rates of acute rejection and infection leading to graft failure have declined. However, the detection of acute and chronic allograft rejection remains one of the most important yet unsettled matters. As such, many new horizons exist for further advancement of the field of heart transplantation and for improving the outcomes of the patients we serve.     

Dual targeting of TNF-α and free radical toxic stress as a promising strategy to manage experimental polycystic ovary

Context: It is now clear that oxidative stress (OS) and chronic low-grade inflammation are two main pathways involved in polycystic ovary syndrome (PCOS) pathogenesis. Therefore, simultaneous targeting of these pathways by means of carvedilol and Semelil (ANGIPARS?), as established medicines with dual anti-cytokine and anti-oxidant potential may be a therapeutic alternative approach to the current treatments.

Objective: The objective of this study is to study the protective effects of carvedilol and ANGIPARS? on inflammatory and oxidative response in hyperandrogenism-induced polycystic ovary (PCO).

Materials and methods: The murine model of PCO was induced by letrozole (1?mg/kg/d; orally) and effective doses of carvedilol (10?mg/kg/d; orally) and ANGIPARS? (2.1?mg/kg/d; orally) were administrated for 21?d in PCO and non-PCO healthy rats. Ovarian folliculogenesis, sex hormones concentrations, OS, inflammatory, and metabolic biomarkers were assessed in serum and ovaries.

Results: PCO rats exhibited ovarian cystogenesis which was preserved by the application of carvedilol and ANGIPARS?. In comparison with controls, decreased level of the total antioxidant power (TAP) and higher levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in serum and ovaries (2.41?±?0.67 versus 0.72?±?0.11; and 0.17?±?0.04 versus 0.05?±?0.01; 5.48?±?1.30 versus 10.56?±?0.77; and 7.06?±?1.94 versus 17.98?±?0.98; p?<?0.05, respectively) were detected in PCO rats. Moreover, the PCO rats exhibited hyperandrogenism due to a 3.7-fold increase in serum testosterone concentration (35.04?±?3.17 versus 131.09?±?13.24; p?<?0.05) along with a 2.98-fold decrease in serum progesterone (6.19?±?0.40 versus 18.50?±?1.03; p?<?0.05) and 5.2-fold decrease in serum estradiol (9.30?±?0.61 versus 48.3?±?2.10; p?<?0.05) when compared with those of the control group. However, similar to the control group, normal levels of OS markers and sex hormones were detected in ANGIPARS? and carvedilol co-treated PCO rats. Besides, when compared with controls, increased levels of TNF-α (770.75?±?42.06 versus 477.14?±?28.77; p?<?0.05) and insulin (1.27?±?0.10 versus 0.36?±?0.05; p?<?0.05) in PCO rats were significantly inhibited by carvedilol and ANGIPARS? co-treatment.

Discussion and conclusion: We evidenced the beneficial effects of carvedilol and ANGIPARS? in PCO, which underpin the new alternative approach in using these kinds of medicines in female reproductive disorders.     

Extracorporeal Life Support for Refractory Cardiac Arrest from Accidental Hypothermia: A 10-Year Experience in Edinburgh

Background

Cardiac arrest caused by accidental hypothermia is a rare phenomenon with a significant mortality rate if untreated. The consensus is that these patients should be rewarmed with extracorporeal life support (ECLS) with the potential for excellent survival and neurologic outcomes. However, given the lack of robust data and clinical trials, the optimal management of such patients remains elusive.

Health and Diabetes Self-efficacy: A Study of Diabetic and Non-diabetic Free Clinic Patients and Family Members

Free clinics across the country provide free or reduced fee healthcare to individuals who lack access to primary care and are socio-economically disadvantaged. This study examined perceived health status among diabetic and non-diabetic free clinic patients and family members of the patients. Diabetes self-efficacy among diabetic free clinic patients was also investigated with the goal of developing appropriate diabetes health education programs to promote diabetes self-management. English or Spanish speaking patients and family members (N = 365) aged 18 years or older completed a self-administered survey. Physical and mental health and diabetes self-efficacy were measured using standardized instruments. Diabetic free clinic patients reported poorer physical and mental health and higher levels of dysfunction compared to non-diabetic free clinic patients and family members. Having a family history of diabetes and using emergency room or urgent care services were significant factors that affected health and dysfunction among diabetic and non-diabetes free clinic patients and family members. Diabetic free clinic patients need to receive services not only for diabetes, but also for overall health and dysfunction issues. Diabetes educational programs for free clinic patients should include a component to increase diabetes empowerment as well as the knowledge of treatment and management of diabetes. Non-diabetic patients and family members who have a family history of diabetes should also participate in diabetes education. Family members of free clinic patients need help to support a diabetic family member or with diabetes prevention.     

Atorvastatin attenuates TNBS-induced rat colitis: the involvement of the TLR4/NF-kB signaling pathway

Aim

The aim of the present study is to explore whether atorvastatin improves intestinal inflammation through the inhibition of the TLR4/NFkB signaling pathway in TNBS-induced rat colitis.

Methods

Acute colitis was induced by intra-rectal administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50 % ethanol. Twenty four hours after colitis induction, saline, atorvastatin (20 and 40 mg/kg) and sulfasalazine (100 mg/kg) were given to the animals by oral route. This was repeated daily for 1 week. Body weight changes, macroscopic and microscopic lesions were assessed. MPO and TNF-α activities were detected by immunohistochemistry (IHC) and the expression level of TLR4, MyD88 and NF-κB p65 proteins were measured by western blotting analysis.

Results

Atorvastatin and sulfasalazine reduced the body weight loss, macroscopic and microscopic lesions. Additionally, both drugs decreased the expression of MPO and TNF-α positive cells in the colon tissue. Furthermore, they inhibited the TNBS-induced expression of TLR4, MyD88 and NF-κB p65 proteins.

Conclusions

It is suggested that the anti-inflammatory effect of atorvastatin on TNBS-induced rat colitis may involve the inhibition of the TLR4/NFkB signaling pathway.

     

Medical students' viewpoint regarding the integrated module of basal ganglia

Integration is an important educational strategy in medical education. Considering this idea, the goal of the present study was to design and implementation of longitudinal and vertical integrated education of anatomy, physiology, pharmacology, neurology and neuropsychiatry subjects of brain's basal ganglia by a multidisciplinary team. Kern's approach to curriculum development was used. Participants were 20 medical students at basic science level who contribute in a 10 stations of pre-test exam at Medical School's Skill Lab. After the implementation of the module by a multidisciplinary team, post-test were done. A structured questionnaire was designed to assess student opinions about adequacy, usefulness of the module using a Likert scale with 5 categories ranging from "completely agreement" to "completely disagreement". The result of pre and post-test were also compared. Twenty questionnaires were completed, giving a 77.63% satisfaction rate. Seventy-five percent of students found it useful and appropriate at basic science level. About fifty percent of students suggested the implementation of this module for other medical students. The score of post-test was significantly (14.52 ± 0.47 vs 6.32 ± 0.62, P < 0.05) higher than pre-test results. The viewpoints of medical students were positive and they value the module highly. Since it is not easy to change the style we teach, these results suggest necessitate of supporting the faculty member's participation in these modules.