IU Indianapolis ScholarWorks :: Browsing by Author "Alloosh, Mouhamad"

Browsing by Author "Alloosh, Mouhamad"

Now showing 1 - 10 of 22

18F-NaF and 18F-FDG as molecular probes in the evaluation of atherosclerosis
(Springer Nature, 2018-11) McKenney-Drake, Mikaela L.; Moghbel, Mateen C.; Paydary, Koosha; Alloosh, Mouhamad; Houshmand, Sina; Moe, Sharon; Salavati, Ali; Sturek, Jeffrey M.; Territo, Paul R.; Weaver, Connie; Werner, Thomas J.; Høilund-Carlsen, Poul Flemming; Sturek, Michael; Alavi, Abass; Cellular and Integrative Physiology, School of Medicine
The early detection of atherosclerotic disease is vital to the effective prevention and management of life-threatening cardiovascular events such as myocardial infarctions and cerebrovascular accidents. Given the potential for positron emission tomography (PET) to visualize atherosclerosis earlier in the disease process than anatomic imaging modalities such as computed tomography (CT), this application of PET imaging has been the focus of intense scientific inquiry. Although 18F-FDG has historically been the most widely studied PET radiotracer in this domain, there is a growing body of evidence that 18F-NaF holds significant diagnostic and prognostic value as well. In this article, we review the existing literature on the application of 18F-FDG and 18F-NaF as PET probes in atherosclerosis and present the findings of original animal and human studies that have examined how well 18F-NaF uptake correlates with vascular calcification and cardiovascular risk.
Adult Ossabaw Pigs Prefer Fermented Sorghum Tea over Isocaloric Sweetened Water
(MDPI, 2023-10-18) Nelson, Catherine E.; Aramouni, Fadi M.; Goering, Mikayla J.; Bortoluzzi, Eduarda M.; Knapp, Laura A.; Herrera-Ibata, Diana M.; Li, Ka Wang; Jermoumi, Rabia; Hooker, Jane A.; Sturek, Joshua; Byrd, James P; Wu, Hui; Trinetta, Valentina; Alloosh, Mouhamad; Sturek, Michael; Jaberi-Douraki, Majid; Hulbert, Lindsey E.; Cellular and Integrative Physiology, School of Medicine
Ossabaw pigs (n = 11; 5-gilts, 6-barrows; age 15.6 ± 0.62 SD months) were exposed to a three-choice preference maze to evaluate preference for fermented sorghum teas (FSTs). After conditioning, pigs were exposed, in four sessions, to choices of white FST, sumac FST, and roasted sumac-FST. Then, pigs were exposed, in three sessions, to choices of deionized H2O (-control; avoidance), isocaloric control (+control; deionized H2O and sucrose), and blended FST (3Tea) (equal portions: white, sumac, and roasted sumac). When tea type was evaluated, no clear preference behaviors for tea type were observed (p > 0.10). When the 3Tea and controls were evaluated, pigs consumed minimal control (p < 0.01;18.0 ± 2.21% SEM), and they consumed great but similar volumes of +control and 3Tea (96.6 and 99.0 ± 2.21% SEM, respectively). Likewise, head-in-bowl duration was the least for -control, but 3Tea was the greatest (p < 0.01; 5.6 and 31.9 ± 1.87% SEM, respectively). Head-in-bowl duration for +control was less than 3Tea (p < 0.01; 27.6 vs. 31.9 ± 1.87% SEM). Exploration duration was the greatest in the area with the -control (p < 0.01; 7.1 ± 1.45% SEM), but 3Tea and +control exploration were not different from each other (1.4 and 3.0 ± 1.45% SEM, respectively). Regardless of tea type, adult pigs show preference for FST, even over +control. Adult pigs likely prefer the complexity of flavors, rather than the sweetness alone.
Animal Models for COVID-19: More to the Picture Than ACE2, Rodents, Ferrets, and Non-human Primates. A Case for Porcine Respiratory Coronavirus and the Obese Ossabaw Pig
(Frontiers Media, 2020-09-25) Heegaard, Peter M. H.; Sturek, Michael; Alloosh, Mouhamad; Belsham, Graham J.; Anatomy and Cell Biology, School of Medicine
The ongoing COVID-19 pandemic caused by infection with SARS-CoV-2 has created an urgent need for animal models to enable study of basic infection and disease mechanisms and for development of vaccines, therapeutics, and diagnostics. Most research on animal models for COVID-19 has been directed toward rodents, transgenic rodents, and non-human primates. The primary focus has been on the angiotensin-converting enzyme 2 (ACE2), which is a host cell receptor for SARS-CoV-2. Among investigated species, irrespective of ACE2 spike protein binding, only mild (or no) disease has occurred following infection with SARS-CoV-2, suggesting that ACE2 may be necessary for infection but is not sufficient to determine the outcome of infection. The common trait of all species investigated as COVID models is their healthy status prior to virus challenge. In contrast, the vast majority of severe COVID-19 cases occur in people with chronic comorbidities such as diabetes, obesity, and/or cardiovascular disease. Healthy pigs express ACE2 protein that binds the viral spike protein but they are not susceptible to infection with SARS-CoV-2. However, certain pig breeds, such as the Ossabaw pig, can reproducibly be made obese and show most aspects of the metabolic syndrome, thus resembling the more than 80% of the critically ill COVID-19 patients admitted to hospitals. We urge considering infection with porcine respiratory coronavirus of metabolic syndrome pigs, such as the obese Ossabaw pig, as a highly relevant animal model of severe COVID-19.
Biphasic alterations in coronary smooth muscle Ca2+ regulation in a repeat cross-sectional study of coronary artery disease severity in metabolic syndrome
(Elsevier, 2016-06) McKenney-Drake, Mikaela L.; Rodenbeck, Stacey D.; Owen, Meredith K.; Schultz, Kyle A.; Alloosh, Mouhamad; Tune, Johnathan D.; Sturek, Michael; Department of Cellular and Integrative Physiology, School of Medicine
BACKGROUND AND AIMS: Coronary artery disease (CAD) is progressive, classified by stages of severity. Alterations in Ca(2+) regulation within coronary smooth muscle (CSM) cells in metabolic syndrome (MetS) have been observed, but there is a lack of data in relatively early (mild) and late (severe) stages of CAD. The current study examined alterations in CSM Ca(2+) regulation at several time points during CAD progression. METHODS: MetS was induced by feeding an excess calorie atherogenic diet for 6, 9, or 12 months and compared to age-matched lean controls. CAD was measured with intravascular ultrasound (IVUS). Intracellular Ca(2+) was assessed with fura-2. RESULTS: IVUS revealed that the extent of atherosclerotic CAD correlated with the duration on atherogenic diet. Fura-2 imaging of intracellular Ca(2+) in CSM cells revealed heightened Ca(2+) signaling at 9 months on diet, compared to 6 and 12 months, and to age-matched lean controls. Isolated coronary artery rings from swine fed for 9 months followed the same pattern, developing greater tension to depolarization, compared to 6 and 12 months (6 months = 1.8 ± 0.6 g, 9 months = 5.0 ± 1.0 g, 12 months = 0.7 ± 0.1 g). CSM in severe atherosclerotic plaques showed dampened Ca(2+) regulation and decreased proliferation compared to CSM from the wall. CONCLUSIONS: These CSM Ca(2+) regulation data from several time points in CAD progression and severity help to resolve the controversy regarding up-vs. down-regulation of CSM Ca(2+) regulation in previous reports. These data are consistent with the hypothesis that alterations in sarcoplasmic reticulum Ca(2+) contribute to progression of atherosclerotic CAD in MetS.
Comparative Quantification of Arterial Lipid by Intravascular Photoacoustic-Ultrasound Imaging and Near-Infrared Spectroscopy-Intravascular Ultrasound
(Springer, 2018-11-28) Kole, Ayeeshik; Cao, Yingchun; Hui, Jie; Bolad, Islam A.; Alloosh, Mouhamad; Cheng, Ji-Xin; Sturek, Michael; Cellular and Integrative Physiology, School of Medicine
Intravascular photoacoustic-ultrasound (IVPA-US) imaging and near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) are two hybrid modalities that detect arterial lipid, with comparison necessary to understand the relative advantages of each. We performed in vivo and ex vivo IVPA-US imaging of the iliac arteries of Ossabaw swine with metabolic syndrome (MetS) and lean swine to investigate sensitivity for early-stage atherosclerosis. We repeated imaging ex vivo with NIRS-IVUS for comparison to IVPA-US and histology. Both modalities showed significantly greater lipid in MetS vs. lean swine, but only IVPA-US localized the lipid as perivascular. To investigate late-stage atherosclerosis, we performed ex vivo IVPA-US imaging of a human coronary artery with comparison to NIRS-IVUS and histology. Two advanced fibroatheromas were identified, with agreement between IVPA-measured lipid area and NIRS-derived lipid content. As confirmed histologically, IVPA-US has sensitivity to detect lipid content similar to NIRS-IVUS and provides additional depth resolution, enabling quantification and localization of lipid cores within plaques.
Effect of Age on Diabetogenicity of Alloxan in Ossabaw Miniature Swine
(American Association for Laboratory Animal Science, 2019-04-01) Badin, Jill K.; Progar, Victor; Pareddy, Anisha; Cagle, Jordan; Alloosh, Mouhamad; Sturek, Michael; Cellular and Integrative Physiology, School of Medicine
According to a single study in dogs that was conducted in 1949, the diabetic effects of the β-cell toxin alloxan are dependent on age. The current study examined whether this age-dependence of alloxan is present in the clinically relevant Ossabaw miniature swine (Sus scrofa domestica) model of metabolic syndrome. Juvenile swine (n = 8; age, 4.3 ± 0.2 mo) and adult swine (n = 8; age, 7.4 ± 0.2 mo) received alloxan (average dosage, 140 mg/kg IV) and were placed on a hypercaloric, atherogenic diet for 6 mo. The metabolic syndrome profile was confirmed by measuring body weight, cholesterol, and triglycerides. Intravenous glucose tolerance testing was used to assess glucose clearance and peripheral plasma insulin levels. The β-cell mass was calculated by immunohistochemical staining of pancreatic tissue. Although juvenile and adult swine exhibited comparable severity of metabolic syndrome, adult swine developed impaired glucose clearance and elevated fasting blood glucose levels at 6 mo after alloxan administration on the atherogenic diet. Peripheral plasma insulin levels in juvenile and adult swine were comparable at all time points and lower than in nonalloxan-treated age-matched controls, which is reflected in the lower pancreatic β-cell mass of the 2 treated groups. However, compared with adult pigs, juvenile swine exhibited greater insulin response recovery (complete or partial restoration of peripheral insulin levels to reference values) at 6 mo after alloxan administration. Overall, these results indicate that youth can confer some protection against the diabetogenic effects of alloxan in swine, potentially due in part to the greater insulin response recovery of young pigs. This study supports previous research that the effects of alloxan are dependent on the developmental maturity of the animal.
Effect of different obesogenic diets on pancreatic histology in Ossabaw miniature swine
(Wolters Kluwer, 2011-04) Fullenkamp, Allison M.; Bell, Lauren N.; Robbins, Reiesha D.; Lee, Lydia; Saxena, Romil; Alloosh, Mouhamad; Klaunig, James E.; Mirmira, Raghavendra G.; Sturek, Michael; Chalasani, Naga; Department of Medicine, IU School of Medicine
OBJECTIVE: Obesity is a factor in the outcome and severity of pancreatic conditions. We examined the effect of hypercaloric diets on the pancreata of Ossabaw swine, a large animal model of metabolic syndrome and obesity. METHODS: Swine were fed with 1 of 4 diets: high-fructose (n = 9), atherogenic (n = 10), modified atherogenic (n = 6), or eucaloric standard diet (n = 12) for 24 weeks. Serum chemistries were measured, and pancreata were examined for histological abnormalities including steatosis, inflammation or fibrosis, insulin content, and oxidative stress. RESULTS: The fructose, atherogenic, and modified atherogenic diet groups exhibited obesity, metabolic syndrome, islet enlargement, and significantly increased pancreatic steatosis (22.9% ± 7.5%, 19.7% ± 7.7%, and 38.7% ± 15.3% fat in total tissue area, respectively) compared with controls (9.3% ± 1.9%; P < 0.05). The modified atherogenic diet group showed significantly increased oxidative stress levels as evidenced by elevated serum malondialdehyde (3.0 ± 3.3 vs 1.5 ± 0.3 μmol/L in controls; P = 0.006) and pancreatic malondialdehyde (0.1 ± 0.12 vs 0.04 ± 0.01 nmol/mg protein in controls; P = 0.01). None of the swine exhibited pancreatitis or cellular injury. CONCLUSIONS: Ossabaw swine fed with a modified atherogenic diet developed significant pancreatic steatosis and increased oxidative stress, but no other histological abnormalities were observed.
Effect of renal shock wave lithotripsy on the development of metabolic syndrome in a juvenile swine model: a pilot study
(Elsevier, 2015-04) Handa, Rajash K.; Liu, Ziyue; Connors, Bret A.; Alloosh, Mouhamad; Basile, David P.; Tune, Johnathan D.; Sturek, Michael; Evan, Andrew P.; Lingeman, James E.; Department of Anatomy & Cell Biology, IU School of Medicine
PURPOSE: We performed a pilot study to assess whether renal shock wave lithotripsy influences metabolic syndrome onset and severity. MATERIALS AND METHODS: Three-month-old juvenile female Ossabaw miniature pigs were treated with shock wave lithotripsy (2,000 shock waves at 24 kV with 120 shock waves per minute in 2) or sham shock wave lithotripsy (no shock waves in 2). Shock waves were targeted to the upper pole of the left kidney to model treatment that would also expose the pancreatic tail to shock waves. Pigs were then instrumented to directly measure arterial blood pressure via an implanted radiotelemetry device. They later received a hypercaloric atherogenic diet for about 7 months. Metabolic syndrome development was assessed by the intravenous glucose tolerance test. RESULTS: Metabolic syndrome progression and severity were similar in the sham treated and lithotripsy groups. The only exception arterial blood pressure, which remained relatively constant in sham treated pigs but began to increase at about 2 months towards hypertensive levels in lithotripsy treated pigs. Metabolic data on the 2 groups were pooled to provide a more complete assessment of metabolic syndrome development and progression in this juvenile pig model. The intravenous glucose tolerance test revealed substantial insulin resistance with impaired glucose tolerance within 2 months on the hypercaloric atherogenic diet with signs of further metabolic impairment at 7 months. CONCLUSIONS: These preliminary results suggest that renal shock wave lithotripsy is not a risk factor for worsening glucose tolerance or diabetes mellitus onset. However, it appears to be a risk factor for early onset hypertension in metabolic syndrome.
Effects of Obesity and Metabolic Syndrome on Steroidogenesis and Folliculogenesis in the Female Ossabaw Mini-Pig
(Public Library of Science, 2015) Newell-Fugate, Annie E.; Taibl, Jessica N.; Alloosh, Mouhamad; Sturek, Michael; Bahr, Janice M.; Nowak, Romana A.; Krisher, Rebecca L.; Department of Cellular and Integrative Physiology, IU School of Medicine
The discrete effects of obesity on infertility in females remain undefined to date. To investigate obesity-induced ovarian dysfunction, we characterized metabolic parameters, steroidogenesis, and folliculogenesis in obese and lean female Ossabaw mini-pigs. Nineteen nulliparous, sexually mature female Ossabaw pigs were fed a high fat/cholesterol/fructose diet (n=10) or a control diet (n=9) for eight months. After a three-month diet-induction period, pigs remained on their respective diets and had ovarian ultrasound and blood collection conducted during a five-month study period after which ovaries were collected for histology, cell culture, and gene transcript level analysis. Blood was assayed for steroid and protein hormones. Obese pigs developed abdominal obesity and metabolic syndrome, including hyperglycemia, hypertension, insulin resistance and dyslipidemia. Obese pigs had elongated estrous cycles and hyperandrogenemia with decreased LH, increased FSH and luteal phase progesterone, and increased numbers of medium, ovulatory, and cystic follicles. Theca cells of obese, compared to control, pigs displayed androstenedione hypersecretion in response to in vitro treatment with LH, and up-regulated 3-beta-hydroxysteroid dehydrogenase 1 and 17-beta-hydroxysteroid dehydrogenase 4 transcript levels in response to in vitro treatment with LH or LH + insulin. Granulosa cells of obese pigs had increased 3-beta-hydroxysteroid dehydrogenase 1 transcript levels. In summary, obese Ossabaw pigs have increased transcript levels and function of ovarian enzymes in the delta 4 steroidogenic pathway. Alterations in LH, FSH, and progesterone, coupled with theca cell dysfunction, contribute to the hyperandrogenemia and disrupted folliculogenesis patterns observed in obese pigs. The obese Ossabaw mini-pig is a useful animal model in which to study the effects of obesity and metabolic syndrome on ovarian function and steroidogenesis. Ultimately, this animal model may be useful toward the development of therapies to improve fertility in obese and/or hyperandrogenemic females or in which to examine the effects of obesity on the maternal-fetal environment and offspring health.
Epicardial Adipose Tissue Removal Potentiates Outward Remodeling and Arrests Coronary Atherogenesis
(Elsevier, 2017-05) McKenney-Drake, Mikaela L.; Rodenbeck, Stacey D.; Bruning, Rebecca S.; Kole, Ayeeshik; Yancey, Kyle W.; Alloosh, Mouhamad; Sacks, Harold S.; Sturek, Michael; Cellular and Integrative Physiology, School of Medicine
BACKGROUND: Pericoronary epicardial adipose tissue (cEAT) serves as a metabolic and paracrine organ that contributes to inflammation and is associated with macrovascular coronary artery disease (CAD) development. Although there is a strong correlation in humans between cEAT volume and CAD severity, there remains a paucity of experimental data demonstrating a causal link of cEAT to CAD. The current study tested the hypothesis that surgical resection of cEAT attenuates inflammation and CAD progression. METHODS: Female Ossabaw miniature swine (n = 12) were fed an atherogenic diet for 8 months and randomly allocated into sham (n = 5) or adipectomy (n = 7) groups. Both groups underwent a thoracotomy, opening of the pericardial sac, and placement of radioopaque clips to mark the proximal left anterior descending artery. Adipectomy swine underwent removal of 1 to 1.5 cm2 of cEAT from the proximal artery. After sham or adipectomy, CAD severity was assessed with intravascular ultrasonography. Swine recovered for an additional 3 months on an atherogenic diet, and CAD was assessed immediately before euthanasia. Artery sections were processed for histologic and immunohistochemical analysis. RESULTS: Severity of CAD as assessed by percent stenosis was reduced in the adipectomy cohort compared with shams; however, plaque size remained unaltered, whereas larger plaque sizes developed in sham-operated swine. Adipectomy resulted in an expanded arterial diameter, similar to the Glagov phenomenon of positive outward remodeling. No differences in inflammatory marker expression were observed. CONCLUSIONS: These data indicate that cEAT resection did not alter inflammatory marker expression, but arrested CAD progression through increased positive outward remodeling and arrest of atherogenesis.

Browsing by Author "Alloosh, Mouhamad"

Results Per Page

Sort Options