- Hemoglobin structure and function
- Adipose Tissue and Metabolism
- Hemoglobinopathies and Related Disorders
- Diet and metabolism studies
- Erythrocyte Function and Pathophysiology
- Traumatic Brain Injury and Neurovascular Disturbances
- Cardiac Arrest and Resuscitation
- Heme Oxygenase-1 and Carbon Monoxide
- Muscle metabolism and nutrition
- Adipokines, Inflammation, and Metabolic Diseases
- Liver Disease Diagnosis and Treatment
- Exercise and Physiological Responses
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- High Altitude and Hypoxia
- Genetics and Physical Performance
- Neuroscience of respiration and sleep
- Birth, Development, and Health
- Advanced MRI Techniques and Applications
- Diet, Metabolism, and Disease
- Neonatal Health and Biochemistry
- Cardiovascular and exercise physiology
- Erythropoietin and Anemia Treatment
- Pharmacology and Obesity Treatment
- Blood groups and transfusion
- Hormonal and reproductive studies
University of California, San Diego
2019-2024
La Jolla Bioengineering Institute
2020-2024
King's College Hospital
2023
Azienda Unità Sanitaria Locale Della Romagna
2023
Manchester University NHS Foundation Trust
2023
IQVIA (United Kingdom)
2023
Universidade de São Paulo
2015-2021
The Ohio State University
2021
Universidade Presbiteriana Mackenzie
2012-2019
University of San Diego
2019
Aim: We investigated the renal lipotoxicity in adult rats exposed to high-fat diet since post-weaning. Main Methods: Male Wistar were divided into two groups: ND (normal diet; n=10) and HD (high fat n=10). The high was introduced post weaned animals followed for 8 weeks. Key Findings: group did not change body weight gain even though food consumption has decreased with no changes caloric consumption. showed glucose intolerance insulin resistance. glomerular filtration rate vivo (ND:...
We investigate the effects of aerobic exercise training (AET) on thermogenic response, substrate metabolism and renin angiotensin system (RAS) in subcutaneous white adipose tissue (SC-WAT) mice fed cafeteria diet (CAF). Male C57BL/6J were assigned into groups CHOW-SED (chow diet, sedentary; n = 10), CHOW-TR trained; CAF-SED (CAF, 10) CAF-TR 10). AET consisted running sessions 60 min at 60% maximal speed, five days per week for eight weeks. The group showed higher body weight adiposity,...
The brown adipose tissue (BAT) mediates adaptive changes in metabolic rate by responding to the sympathetic nervous system through β-adrenergic receptors (AR). Here, we wished define role played ARβ3 isoform this process. This study focused on knockout mice (ARβ3KO), including responsiveness cold exposure, diet-induced obesity, intolerance glucose, dyslipidaemia and lipolysis white (WAT). ARβ3KO defend core temperature during exposure (4°C for 5 h), with faster BAT thermal response...
Abstract Traumatic brain injury (TBI) is often accompanied by hemorrhage, and treatment of hemorrhagic shock (HS) after TBI particularly challenging because the two therapeutic strategies for HS conflict. Ischemia/reperfusion from resuscitation can be exaggerated TBI-induced loss autoregulation. In resuscitation, goal to restore lost blood volume, while in priority focused on maintenance adequate cerebral perfusion pressure avoidance secondary bleeding. this study, we investigate responses...
ABSTRACT Background: Hemoglobin (Hb)-based oxygen carriers (HBOCs) have been proposed as alternatives to blood for decades. Previous studies demonstrated that large molecular diameter HBOCs based on polymerized bovine Hb (PolybHb) attenuate side-effects and toxicity. The objective of this study was test the safety efficacy tense state PolybHb after long-term storage. Methods Results: subjected diafiltration remove low weight (< 500 kDa) species stored 2 years. studied in parallel with...
Summary The pathophysiologic mechanism of sickle cell disease (SCD) involves polymerization deoxygenated haemoglobin S (HbS), leading to red blood (RBC) sickling, decreased RBC deformability, microvascular obstruction, haemolysis, anaemia and downstream clinical complications. Pharmacological increase in the concentration oxygenated HbS RBCs has been shown be a novel approach inhibit reduce sickling haemolysis. We report that GBT021601, small molecule increases HbS‐oxygen affinity, inhibits...
Acclimatization to hypoxia or high altitude involves physiological adaptation processes, influence oxygen (O2) transport and utilization. Several natural products, including aromatic aldehydes isothiocyanates stabilize the R-state of hemoglobin (Hb), increasing Hb O2 affinity saturation. These products are a counter intuitive therapeutic strategy increase delivery during hypoxia. 5-Hydroxymethylfurfural (5-HMF) is well known Amadori compound formed Maillard reaction (the non-enzymatic...
This study aims to investigate the effects of hypoxically stored Red Blood Cells (RBCs) in a rat model traumatic brain injury followed by severe hemorrhagic shock and resuscitation. RBCs were made hypoxic using an O2 depletion system (Hemanext Inc. Lexington, MA) for 3 weeks. Experimental group animals underwent craniotomy blunt HS. Rats resuscitated with either fresh (FRBCs), 3-week-old (HRBCs), or conventionally (CRBCs). Resuscitation was provided via RBC transfusion equivalent 70 % shed...
Non-alcoholic fatty liver disease (NAFLD) is one of the most common forms disease, which associated with several etiological factors, including stress and dysfunction in oxidative metabolism. However, studies showed that aerobic exercise training (AET) can combat (OS) improves mitochondrial functionality NAFLD. To test hypothesis AET metabolism antioxidant defense ob/ob mice. Male mice eight weeks old were separated into two groups: sedentary group (S), n=7, trained (T), n=7. The T submitted...
Hemoglobin (Hb)-based oxygen (O2) carriers (HBOCs) have been developed as an alternative to red blood cells (RBCs) for use in transfusion medicine. HBOCs many benefits over RBCs; however, previous generations of failed clinical trials due unanticipated cardiotoxicity. These problems likely originated from vasoconstriction, hypertension, oxidative stress, and the presence low-molecular-weight (MW) Hb species HBOC formulation. Therefore, objective this study is compare toxicity small-MW...
Therapeutic agents that increase the Hb affinity for oxygen (O2) could, in theory, lead to decreased O2 release from and impose a hypoxic risk tissues. In this study, GBT1118, an allosteric modifier of O2, was used assess impact increasing on brain tissue oxygenation, blood pressure, heart rate, delivery, tolerance hypoxia Townes transgenic sickle cell disease (SCD) mice. Brain oxygenation delivery were studied during normoxia severe challenges. Chronic treatment with GBT1118 increased...
For the past thirty years, hemoglobin-based oxygen carriers (HBOCs) have been under development as a red blood cell substitute. Side-effects such vasoconstriction, oxidative injury, and cardiac toxicity prevented clinical approval of HBOCs. Recently, high molecular weight (MW) polymerized human hemoglobin (PolyhHb) has shown positive results in rats. Studies demonstrated that MW PolyhHb increased O
Easy access to high-calorie and fat-dense fast food has resulted in unhealthy dietary lifestyle changes worldwide, which affects both developed developing economies. This predisposes populations a considerable number of metabolic inflammatory conditions, such as diabetes, nonalcoholic fatty liver disease (NAFLD), cardiovascular (CVD). Guinea pigs have been proposed model study high-fat diet-induced due their similar antioxidant metabolism lipid profile humans, susceptibility atherosclerosis...
Introduction: The demand for red blood cells (RBCs) is on the rise due to increasing diagnosis of chronic diseases such as sickle cell anemia, malaria, and thalassemia. Despite many commercial attempts, there are no U.S. FDA-approved artificial RBCs use in humans. Existing RBC substitutes have employed various strategies transport oxygen, extend circulation time, reduce organ toxicity, but none replicated natural protective mechanisms RBCs, which prevent hemoglobin (Hb) dimerization heme...
Abstract Background Hemoglobin (Hb)‐based oxygen (O 2 ) carriers (HBOCs) are being developed as alternatives to red blood cells and when these products unavailable. Clinical trials of previous HBOC generations revealed side effects, including hypertension vasoconstriction, that were not observed in preclinical studies. Large molecular weight (MW) polymerized bovine Hb (PolybHb) represents a new class with promising results. We evaluated the safety profile PolybHb after an exchange...
The present study aimed to compare the ability of tense (T) and relaxed (R) quaternary state polymerized human hemoglobin (PolyhHb) restore hemodynamics after severe trauma in a rat model, assess their relative toxicity guinea pigs (GPs). To efficacy these PolyhHbs restoring hemodynamics, Wistar rats were subjected traumatic brain injury (TBI) followed by hemorrhagic shock (HS). Animals separated into 3 groups based on resuscitation solution: Whole blood, T-state or R-state PolyhHb, for 2...
Alternatives to blood for use in transfusion medicine have been investigated decades. An ideal alternative should improve oxygen (O2)-carrying capacity and O2 delivery support microvascular flow. Previous studies shown that large-molecular diameter hemoglobin (Hb)-based carriers (HBOCs) based on polymerized bovine Hb (PolybHb) reduce the toxicity vasoconstriction of first-generation HBOCs by increasing plasma viscosity preserving perfusion. The objective this study was examine impact PolybHb...