Adaptations to Chronic Hypoxia Combined with Erythropoietin Deficiency in Cerebral and Cardiac Tissues

Chronic anemia-induced hypoxia triggers regulatory pathways that mediate long-term adaptive cardiac and cerebral changes, particularly at the transcriptional level. These adaptative mechanisms include a regulated cerebral blood flow and cardiac output, angiogenesis and cytoprotection triggered by hypoxia-inducible factor 1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), neuronal nitric oxide synthase (nNOS) and Epo pathways. All these compensatory mechanisms aim to optimize oxygen delivery and to protect the brain and heart from hypoxic injury. We reviewed the effects of chronic hypobaric hypoxia as well as chronic anemia in the heart and brain, and we compared for the first time the effects of chronic hypobaric hypoxia combined with a severe lack of Epo (chronic anemia) in these vital organs. Functional cardiac adaptations such as cardiac hypertrophy, increased cardiac output as well as angiogenesis occurred along with the activation of HIF1α/VEGF and Epo/EpoR pathways under chronic anemia or hypoxia. Similarly, cerebrovascular adaptations take place through the same molecular mechanisms under chronic hypoxia or anemia. However, when both arterial pressure and content of oxygen are decreased, the cerebral and cardiac adaptative mechanisms showed their limitations. In addition, cerebral and cardiac cell injuries may have occurred following the combined effect of chronic anemia and hypoxia. By emphasizing the anemia and hypoxia-induced cerebral and myocardial adaptations, this review highlighted the crucial role of Epo in its non-erythropoietic functions such as angiogenesis and neuroprotection. Indeed, a better understanding of these protective mechanisms is of great clinical importance to the development of new therapeutic strategies for the management of ischemic heart and brain

Epo Is Relevant Neither for Microvascular Formation Nor for the New Formation and Maintenance of Mice Skeletal Muscle Fibres in Both Normoxia and Hypoxia

Erythropoietin (Epo) and vascular growth factor (VEGF) are known to be involved in the regulation of cellular activity when oxygen transport is reduced as in anaemia or hypoxic conditions. Because it has been suggested that Epo could play a role in skeletal muscle development, regeneration, and angiogenesis, we aimed to assess Epo deficiency in both normoxia and hypoxia by using an Epo-deficient transgenic mouse model (Epo-TAgh). Histoimmunology, ELISA and real time RT-PCR did not show any muscle fiber atrophy or accumulation of active HIF-1α but an improvement of microvessel network and an upregulation of VEGFR2 mRNA in Epo-deficient gastrocnemius compared with Wild-Type one. In hypoxia, both models exhibit an upregulation of VEGF120 and VEGFR2 mRNA but no accumulation of Epo protein. EpoR mRNA is not up-regulated in both Epo-deficient and hypoxic gastrocnemius. These results suggest that muscle deconditioning observed in patients suffering from renal failure is not due to Epo deficiency

What is known about Ventricular Septal Defect in University Female Students of Saudi Arabia?

This study was performed to estimate the knowledge and awareness of the university students about the presence of ventricular septal defects (VSDs) in Saudi Arabia. A cross-sectional study was performed in Princess Nourah bint Abdulrahman University (PNU) campus where a total of 350 female students in the age group of 17-25 years were surveyed using a clinically appropriate structurally designed questionnaire. Only a third of the population were familiar with the definition and anatomical location of VSDs. Although, majority of the population believed that VSDs are subject to cure, a negligible population of the students were aware that VSDs are associated with pulmonary hypertension in adults, although, about half of the population were associated with people who were suffering from VSDs. Even though promising, only half of the population were aware of rapid breathing in infants and association of endocarditis with VSDs. Regarding life-style factors, only 18% of the population knew that VSD patients are restrained from different physical activities. This population study is the first of its kind to determine the knowledge of the university students regarding the characteristics, symptoms, risk-factors, management and life-style factors associated with VSD. It identified the imperative need to organize campaigns to raise awareness about the disease process and management among female population who will be future mothers since Awareness about VSDs can help manage the physical, social, cognitive and emotional well-being of the patients with better outcomes to reduce the mortality rate.

Irritable Bowel Syndrome Among Female Students in Princess Nourah University in Kingdom of Saudi Arabia

In this study, our objective was to explore the knowledge of Irritable Bowel syndrome (IBS) among university female students in the Kingdom of Saudi Arabia (KSA). A cross-sectional study was conducted where 307 university students were surveyed using a self-administered questionnaire to assess their awareness. The questionnaire was based on the socio-demographic and life-style characteristics of the students to evaluate the prevalence of IBS in the community.  About 60% of the population in the age group of 18-20 years are at a high risk of suffering from IBS. However, no significant difference is demonstrated between lifestyle habits such as consumption of fast and spicy foods and physical activities and onset of IBS among the students. Nevertheless, frequent episodes of exercise in a week may reduce the probability of IBS onset. Interestingly, almost half of the student population mentioned that they were taking antibiotics and their sleep was interrupted as they woke up in the middle of the night.  Also, majority of the population indicated that their stool texture was different, either hard or loose associated with a pain and distended abdomen followed with gastritis. Abdominal discomfort, feeling of bloating, altered texture of stool and urgency to defecate could be due to the development of psychological stress associated with academics, which possibly intensifies the disease symptoms. Initial findings from our study justifies the need of future longitudinal surveys to validate the existence of psychological stressors and other risk factors in the development of IBS subtypes

Catalyzing role of erythropoietin on the nitric oxide central pathway during the ventilatory responses to hypoxia

International audienceThe N‐Methyl‐d‐Aspartate (NMDA) receptors – neuronal nitric oxide synthase (nNOS) pathway is involved in the ventilatory response to hypoxia. The objective was to assess the possible effect of erythropoietin deficiency and chronic exposure to hypoxia on this pathway during ventilatory response to acute hypoxia. Wild‐type (WT) and erythropoietin‐deficient (Epo‐TAgh) male mice were exposed (14 days) either to hypobaric hypoxia (Pb = 435 mmHg) or to normoxia. The ventilation was measured at 21% or 8% O2 after injection of vehicle (NaCl), nNOS inhibitor (SMTC) or NMDA receptor antagonist (MK‐801). Nitric oxide production and the expression of NMDA receptor and nNOS were assessed by real‐time RT‐PCR and Western blot analyses in the medulla. At rest, Epo‐TAgh mice displayed normal ventilatory parameters at 21% O2 but did not respond to acute hypoxia despite a larger expression of NMDA receptors and nNOS in the medulla. Ventilatory acclimatization to hypoxia was observed in WT but was absent in Epo‐TAgh mice. nNOS inhibition blunted the hypoxic ventilatory acclimatization of WT mice without any effect in Epo‐TAgh mice. Acute hypoxic ventilatory response (HVR) was increased after chronic hypoxia in WT but remained unchanged in Epo‐TAgh mice. Ventilatory response to acute hypoxia was modified by MK‐801 injection in WT and Epo‐TAgh mice. The results confirm that adequate erythropoietin level is necessary to obtain an appropriate HVR and a significant ventilatory acclimatization to hypoxia. Furthermore, erythropoietin plays a potential catalyzing role in the NMDA‐NO central pathway during the ventilatory response and acclimatization to hypoxia