Calcium Homeostasis in Ventricular Myocytes of Diabetic Cardiomyopathy

© 2020 Lina T. Al Kury. Diabetes mellitus (DM) is a chronic metabolic disorder commonly characterized by high blood glucose levels, resulting from defects in insulin production or insulin resistance, or both. DM is a leading cause of mortality and morbidity worldwide, with diabetic cardiomyopathy as one of its main complications. It is well established that cardiovascular complications are common in both types of diabetes. Electrical and mechanical problems, resulting in cardiac contractile dysfunction, are considered as the major complications present in diabetic hearts. Inevitably, disturbances in the mechanism(s) of Ca2+ signaling in diabetes have implications for cardiac myocyte contraction. Over the last decade, significant progress has been made in outlining the mechanisms responsible for the diminished cardiac contractile function in diabetes using different animal models of type I diabetes mellitus (TIDM) and type II diabetes mellitus (TIIDM). The aim of this review is to evaluate our current understanding of the disturbances of Ca2+ transport and the role of main cardiac proteins involved in Ca2+ homeostasis in the diabetic rat ventricular cardiomyocytes. Exploring the molecular mechanism(s) of altered Ca2+ signaling in diabetes will provide an insight for the identification of novel therapeutic approaches to improve the heart function in diabetic patients

EFFECTS OF THE ENDOCANNABINOID ANANDAMIDE ON EXCITABILITY AND CALCIUM SIGNALING IN RAT VENTRICULAR MYOCYTES

Endogenous cannabinoids (endocannabinoids) exert a wide range of biological effects. In addition to having their well-known neurobehavioral effects, a role for the major endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA), in the cardiovascular system in various pathological conditions has been reported. The aim of this thesis is to explore the effects of AEA on contractility, Ca2+ signaling, and action potential (AP) characteristics in rat ventricular myocytes. A video edge detection system was used to measure myocyte shortening. Intracellular Ca2+ was measured in cells loaded with the fluorescent indicator fura-2 AM. AEA (1 μM) caused a significant decrease in the amplitude of electrically-evoked myocyte shortening. The effect of AEA was not altered in the presence of pertussis toxin (PTX), AM251 and SR141716 (CB1 antagonists) or AM630 and SR 144528 (CB2 antagonists). AEA also caused a significant decrease in the amplitudes of electrically-evoked Ca2+ transients. However, the amplitudes of caffeine-evoked Ca2+ transients and the rate of recovery of electrically-evoked Ca2+ transients following caffeine application were not altered. In the whole-cell mode of patch-clamp technique, AEA (1 μM) significantly decreased the duration of APs. The inhibition was not altered in the presence of PTX, AM251 and AM630. Furthermore, AEA inhibited voltage-activated inward Na+ (INa) and Ca2+ (IL,Ca) currents; major ionic currents shaping the APs in ventricular myocytes, in a voltage and PTX-independent manner. Cardiac Na+/Ca2+ exchanger (NCX1)-mediated currents were also suppressed by AEA. The effect of AEA was not influenced by the inhibition of fatty acid amide hydrolase (FAAH) or in the presence of PTX, AM251 and AM630 or following the inclusion of GDP-β-S in pipette solution. The results of this study indicate for the first time that impaired Ca2+ signaling underlies the negative inotropic actions of AEA in rat ventricular myocytes, and that the direct interaction of AEA with ion channel(s) shaping APs, mediates, at least in part, the effects of AEA on myocyte contractility. In addition, the results indicate for the first time that, under normal conditions, AEA can directly inhibit the activity of NCX1 in ventricular myocytes. In view of the massive release of various N-acylethanolamines (NAEs), including AEA, during cardiac ischemia and hypoxic conditions, further understanding of their mechanism(s) of action and target proteins is essential in the development of better treatment modalities under pathological conditions

Use of Herbal Medicine Among the Public in Abu Dhabi

Background: Herbal remedies have been used in traditional medicine for thousands of years to treat various human ailments. Aim: Given the rising increase in the use of herbal products among the United Arab Emirates (UAE) population, this study aims to explore the level of knowledge, attitude, and beliefs about the use of herbal medicine among the public in Abu Dhabi. Methods: A total of 410 male and female participants aged between 20 and 60+ years completed a 20-item face-to-face questionnaire that was composed of three sections. The first section of the questionnaire included demographic data (age, gender, nationality, marital status, and level of education), health status, and familiarity with herbal medicine. The second section included practices of using of herbal medicine among participants. The last section included respondents' beliefs and attitudes about herbal medicine based on its use. Results: The results of this study showed that almost half of the respondents were married and aged between 20 and 29 years. Only one-fifth of the participants were very familiar with the herbal medicine while more than one-third reported no familiarity. The results also showed that about 35% of the participants use herbal medicine. The only demographic features linked with the usage of herbal medications were age and marital state, where married respondents reported higher use of herbal medicine than unmarried. In addition, older respondents (40+ years) reported higher use compared to younger generations. Moreover, the patient's high cholesterol level was the sole connected health-related attribute. Interestingly, most users indicated that herbal medicine was recommended to them by family or friends, followed by herbalists and medical doctors. According to nonusers, the biggest deterrent to utilizing herbal remedies was being healthy and having no need for using herbal medicine, while lack of available information about herbal medicine was the second reason. The highest belief of respondents about the use of herbal medicine was their role in maintaining and promoting health. Conclusion: Although the results of this study showed that herbal medicine is moderately used in UAE, particularly by those who have hypercholesterolemia, it is important to emphasize the benefits and drawbacks of utilizing herbal remedies. Effective herbal medicine policies and health education programs must be developed. Patient counseling and education about medication use are needed to augment their awareness about their use. Keywords: herbal medicine, demographic features, hypercholesterolemi

Breast Cancer Awareness Among Zayed University Female Students

Background/Aim : Breast cancer is one of the most common cancers among female population worldwide. In the United Arab Emirates, breast cancer accounts for 31-43% of all cancer types. Recently, breast cancer incidence has declined as a result of development of better diagnostic techniques. Good knowledge and awareness about early detection of signs and symptoms of the disease are the most important keys for reducing morbidity and mortality. This study aims to evaluate the level of awareness about the risk factors of breast cancer, as well as, the knowledge about screening methods among female students at Zayed University in Abu Dhabi. Method: Â A random cross-sectional survey was carried to evaluate the level of awareness about breast cancer among female students at Zayed University. A total of 100 females aged 18 “31 from different colleges were included in the study. Data were analyzed using SPSS 21 program. Chi- square test was used together with Fisher\u27s exact test, as appropriate. P value \u3c0.05 was considered significant. Results: The results show that there is a lack of knowledge and awareness about the risk factors for breast cancer. Only 12% of the participants knew that physical inactivity is a risk factor. However, 29% of the participants knew that obesity is a risk factor. Knowledge about screening methods was poor and varied according to the marital and educational status of the students. Only 17% of the total participants have done breast self-examination. Single women had less frequently performed breast self-examination compared to married women Although 40% of the participants knew about ultra sound, only 22% of the students did have the knowledge about the proper age of mammogram screening. Conclusion: The results point to the lack of awareness among female students about breast cancer, the risk factors and screening methods. Therefore, effective educational programs are required to improve the knowledge level of university students regarding breast cancer and related practices

Breast Cancer Awareness Among Zayed University Female Students

Background/Aim: Breast cancer is one of the most common cancers among female population worldwide. In the United Arab Emirates, breast cancer accounts for 31-43% of all cancer types. Recently, breast cancer incidence has declined as a result of development of better diagnostic techniques. Good knowledge and awareness about early detection of signs and symptoms of the disease are the most important keys for reducing morbidity and mortality. This study aims to evaluate the level of awareness about the risk factors of breast cancer, as well as, the knowledge about screening methods among female students at Zayed University in Abu Dhabi. Method:  A random cross-sectional survey was carried to evaluate the level of awareness about breast cancer among female students at Zayed University. A total of 100 females aged 18–31 from different colleges were included in the study. Data were analyzed using SPSS 21 program. Chi- square test was used together with Fisher’s exact test, as appropriate. P value <0.05 was considered significant. Results: The results show that there is a lack of knowledge and awareness about the risk factors for breast cancer. Only 12% of the participants knew that physical inactivity is a risk factor. However, 29% of the participants knew that obesity is a risk factor. Knowledge about screening methods was poor and varied according to the marital and educational status of the students. Only 17% of the total participants have done breast self-examination. Single women had less frequently performed breast self-examination compared to married women Although 40% of the participants knew about ultra sound, only 22% of the students did have the knowledge about the proper age of mammogram screening. Conclusion: The results point to the lack of awareness among female students about breast cancer, the risk factors and screening methods. Therefore, effective educational programs are required to improve the knowledge level of university students regarding breast cancer and related practices

Immunomodulatory and anticancer activities of hyacinthus orientalis l.: An in vitro and in vivo study

Hyacinthus orientalis L. (family Hyacinthaceae) is traditionally used to treat different diseases including cancer. In this study, the anticancer and immunomodulatory effects of this plant were evaluated. Hydroalcoholic extract was prepared, and different solvent fractions were obtained using solvent–solvent extraction. In the anticancer part, MTT assay and caspase-3 ELISA kits were used to measure the antiproliferative and apoptosis induction ability for each extract, respectively. In the immunomodulatory part, lymphocyte proliferation assay and cytokines detection kit were used to measure the effect of extracts of acquired immunity. Phagocytosis and pinocytosis induction were used to evaluate the effect of extracts on the innate immunity. GC–MS, LC–MS, and Foline–Ciocalteu assays were used to identify the chemical composition of the plant. Balb/C mice were inoculated with breast cancer and treated with hydroalcoholic extract of H. orientalis L. Results showed that hydroalcoholic extract and n-hexane fraction were highly effective in apoptosis induction. Both extract and fraction were also effective in stimulating lymphocytes proliferation and phagocytosis. Significant reduction in tumor size was achieved after treating tumor-bearing mice with hydroalcoholic extract. Additionally, high cure percentages (50%) were obtained in treated mice. Results of this study showed that H. orientalis L. has promising anticancer and immunomodulatory activities. However, further studies are needed to explore more details of apoptosis induction ability and other mechanisms of action and to measure different signaling pathways responsible for the anticancer and immunomodulatory response

Characterization of L-type calcium channel activity in atrioventricular nodal myocytes from rats with streptozotocin-induced Diabetes mellitus

© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. Cardiovascular complications are common in patients with Diabetes mellitus (DM). In addition to changes in cardiac muscle inotropy, electrical abnormalities are also commonly observed in these patients. We have previously shown that spontaneous cellular electrical activity is altered in atrioventricular nodal (AVN) myocytes, isolated from the streptozotocin (STZ) rat model of type-1 DM. In this study, utilizing the same model, we have characterized the changes in L-type calcium channel activity in single AVN myocytes. Ionic currents were recorded from AVN myocytes isolated from the hearts of control rats and from those with STZ-induced diabetes. Patch-clamp recordings were used to assess the changes in cellular electrical activity in individual myocytes. Type-1 DM significantly altered the cellular characteristics of L-type calcium current. A reduction in peak ICaL density was observed, with no corresponding changes in the activation parameters of the current. L-type calcium channel current also exhibited faster time-dependent inactivation in AVN myocytes from diabetic rats. A negative shift in the voltage dependence of inactivation was also evident, and a slowing of restitution parameters. These findings demonstrate that experimentally induced type-1 DM significantly alters AVN L-type calcium channel cellular electrophysiology. These changes in ion channel activity may contribute to the abnormalities in cardiac electrical function that are associated with high mortality levels in patients with DM

Characterization of L-type calcium channel activity in atrioventricular nodal myocytes from rats with streptozotocin-induced Diabetes mellitus

© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. Cardiovascular complications are common in patients with Diabetes mellitus (DM). In addition to changes in cardiac muscle inotropy, electrical abnormalities are also commonly observed in these patients. We have previously shown that spontaneous cellular electrical activity is altered in atrioventricular nodal (AVN) myocytes, isolated from the streptozotocin (STZ) rat model of type-1 DM. In this study, utilizing the same model, we have characterized the changes in L-type calcium channel activity in single AVN myocytes. Ionic currents were recorded from AVN myocytes isolated from the hearts of control rats and from those with STZ-induced diabetes. Patch-clamp recordings were used to assess the changes in cellular electrical activity in individual myocytes. Type-1 DM significantly altered the cellular characteristics of L-type calcium current. A reduction in peak ICaL density was observed, with no corresponding changes in the activation parameters of the current. L-type calcium channel current also exhibited faster time-dependent inactivation in AVN myocytes from diabetic rats. A negative shift in the voltage dependence of inactivation was also evident, and a slowing of restitution parameters. These findings demonstrate that experimentally induced type-1 DM significantly alters AVN L-type calcium channel cellular electrophysiology. These changes in ion channel activity may contribute to the abnormalities in cardiac electrical function that are associated with high mortality levels in patients with DM

Xanthium spinosum L. Extracts Inhibit Breast Cancer in Mice by Apoptosis Induction and Immune System Modulation

Plants have been considered for many years as an important source of medicine to treat different diseases. Xanthium spinosum L. (Asteraceae, Compositae) is known for its diuretic, anti-inflammatory, and sedative effects. It is also used in the treatment of several ailments, such as cancer. In order to evaluate the anticancer and immunomodulatory activities, crude ethanol extract was prepared from the aerial part of X. spinosum and then fractionated using solvents with different polarities. As well, the chemical composition of X. spinosum extract and fractions were identified using LC-MS analysis. The antitumor effect of X. spinosum was assessed in both in vitro and in vivo models. Apoptosis induction was measured in vitro using a caspase-3 activity kit. Lymphocyte proliferation and phagocytosis and pinocytosis induction were used to quantify the effect of the plant extract and fractions on acquired and innate immunity, respectively. The effect of X. spinosum extract, and fractions on the levels of cytokines (IFN-γ, IL-2, IL-4, and IL-10) in murine lymphocytes was determined using a mouse-uncoated TH1/TH2 ELISA kit. Results showed that ethanol extract had the highest antiproliferative activity (IC₅₀ = 2.5 mg mL−1) against EMT6/P cell lines, while the aqueous and chloroform fractions had the highest apoptotic activity with 2.2 and 1.7 folds, respectively. On the other hand, the n-hexane fraction was the most effective in stimulating lymphocyte proliferation, whereas ethanol extract, aq. Methanol and aqueous fractions exhibited the highest phagocytic activity. As well, X. spinosum extract and fractions were able to modulate the expression of IL-2, IL-4, and IFN-γ. A remarkable decrease in tumor size was accomplished following the treatment of tumor-bearing mice with X. spinosum extract and fractions. Both aq. Methanol and chloroform fractions showed the highest percentage change in tumor size with -58 and -55%, respectively. As well, tumor-bearing mice treated with chloroform fraction demonstrated a high curable percentage with a value of 57.1%. Anyway, X. spinosum extract and fractions exhibited no toxic impact on the liver or kidney functions of the mice-treated groups. These findings may confirm that X. spinosum has favorable anticancer and immunomodulatory effects. However, additional studies are required to fully understand the mechanisms of action of this plant and the signaling pathways involved in its effects. Moreover, more testing is needed to have better insight into the apoptotic pathway and to know the exact concentration of active compounds