published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

No description available.

Thesis (M.S.)--University of Delaware, 2008. / Principal faculty advisor: Cheng-Shun (Richard) Fang, Dept. of Health, Nutrition, & Exercise Sciences. Includes bibliographical references.

This observational study compared bone health biomarkers, bone mineral density (BMD),dietary habits, and physical activity levels of men (n=31) and non-estrogen supplementing postmenopausal women (n=23) divided according to duration of proton pump inhibitor (PPI) therapy; more than 5 years (n=16), less than 5 years (n=15), and no PPI therapy (n=23). The shortest duration of PPI therapy was 2 months and the longest duration of PPI therapy was 25 years with a mean duration of 7.5 years. No significant differences were found between measures of spine BMD, urinary deoxypyridinoline (bone resorption), urinary calcium and magnesium, serum osteocalcin (bone formation), serum parathyroid hormone, serum magnesium, serum 25 hydroxyvitamin D3, dietary and supplement intake, or physical activity levels. However, mean hip BMD was higher in females than in males in participants who took PPI therapy for any duration. In the no PPI therapy group, hip BMD was not significantly different between genders. These results suggest that there may be no measurable or clinically significant negative effects of long term PPI therapy on bone health. However, men may be at higher risk of hip fracture when taking long-term PPI therapy than women.

No description available.

Para avaliar o efeito do uso oral de omeprazol em ruminantes adultos saudáveis, foram utilizados cinco ovinos machos, com dois anos de idade, hígidos e providos de cânula abomasal, que ou não receberam nada (grupo controle) ou receberam omeprazol oral em pasta, na dose de 4 mg/kg de peso vivo a cada 24 horas, durante 7 dias, em delineamento experimental de cross-over, com período de 'wash-out' de 7 dias. Diariamente os animais foram avaliados clinicamente e foram realizados o hemograma, a hemogasometria venosa; a mensuração dos eletrólitos, o perfil bioquímico, a concentração de pepsinogênio e o pH abomasal, urinário e fecal. Foi realizada, no último dia do período experimental a curva de 24 horas, com intervalo de duas horas, para o pH abomasal e o pepsinogênio sérico. Não houve efeito de tratamento para as variáveis analisadas, que permaneceram dentro do intervalo fisiológico para a espécie ovina. O uso do omeprazol na dose de 4 mg/kg de peso corporal durante sete dias, apesar de não aumentar o pH abomasal, diminuiu as concentrações de cálcio iônico e de cloro séricas / To evaluate the effect of oral omeprazole in healthy adult ruminants, five male sheep, two years old, healthy and provided with abomasal cannula, were used. Either received nothing (control group) or received oral omeprazole paste in dose of 4 mg /kg body weight every 24 hours for 7 days in experimental design of cross-over, with period of 'wash-out' of 7 days. Every day the animals were evaluated clinically and were performed the blood test, venous blood gas analysis; the measurement of electrolytes, biochemical profile, the concentration of pepsinogen and abomasal pH, urinary and fecal. It was held in last day trial period to 24 hours curve with an interval of two hours for the abomasal pH and serum pepsinogen. There was no treatment effect for the variables that remained within the physiological range for the sheep. The use of omeprazole at 4 mg / kg body weight for seven days, while not increasing the pH abomasal decreased the calcium ion concentration and serum chlorine

Clostridium difficile (C. difficile) is a gram positive, anaerobic, spore forming bacterium. C. difficile infections are triggered by dysbiosis of the intestinal microbiome linked to age, immune status, and medication; particularly use of antibiotics and proton pump inhibitors (PPI). The spore forming nature of the bacteria gives it the ability to persist in the environment for long periods of time and makes it impervious to many commonly-used hospital cleaning and disinfection products. C. difficile, along with Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococcus (VRE) are some of the leading multi-drug resistant hospital acquired infections in the United States. Environmental contamination and patient susceptibility are hypothesized as major contributors to infection transmission in a healthcare setting. We conducted a cross-sectional pilot study aimed at determining the bioaerosol concentration of C. difficile present in the toilet plume of C. difficile infected patients’ rooms. Patient rooms within the University of Iowa Hospital and Clinics (UIHC) were sampled using a customized bioaerosol air impactor device. Environmental samples were collected before and after flushing the toilet to determine the pre-flush and post-flush levels of aerosolized bacteria. Particle density was collected during both pre and post-flush sampling. Activity levels in the rooms were recorded as a potential confounding variable. A total of 144 environmental samples were collected in 24 rooms. Clostridium difficile was detected in two of the twenty-four rooms (8%). There was a 12% (9/72) positive culture rate pre-flush compared to 23% (19/72) post-flush. Wilcoxon rank sum tests revealed a significant increase in particle concentration at the 5.0µm and 10.0µm size between rooms that produced a bacterial culture compared to rooms that did not (p-values 0.0095 and 0.0082 respectively). There was no significant association between the amount of activity in the room and detectable bioaerosol production (p-value=0.605). Next, we performed a randomized control trial of hospital privacy curtains with antimicrobial properties to determine their ability to resist pathogenic bacterial contamination in an intensive care unit setting. Rooms within the surgical and neurological intensive care unit at UIHC were randomized to receive impregnated curtains, impregnated curtains plus Fuzion hypochlorite spray, or standard control curtains. MRSA, VRE, Pseudomonas spp. and Acinetobacter spp. were the four most frequently cultured pathogenic species. Time to event (contamination) analysis identified a significant difference in time to pathogenic contamination between the control curtains and the impregnated curtains post spray (p-value<0.001). The impregnated curtains post Fuzion spray also grew significantly less colonies of bacteria compared to the control curtains (p-value<0.001). After evaluating environmental risk factors that contribute to Clostridium difficile infection, patient related risk factors for infection were evaluated. Proton pump inhibitors are a class of gastric acid reducers that work by reducing the amount of hydrogen ions produced in the stomach. Recent evidence suggests that prolonged use could negatively affect the intestinal microbiome making it more susceptible to enteric pathogens. A nested case control study was done to determine the association between PPI medication duration and C. difficile infection. Fecal microbiome diversity was analyzed via logistic regression in relation to the development of Clostridium difficile infection. A co-morbidity score was created to adjust for other microbiome altering conditions. PPI duration remained a significant predictor of infection after adjusting for the microbiome influence (p-value=0.0123). Environmental contamination remains a significant risk factor for the transmission of hospital acquired infections including C. difficile. Toilets flushing has been shown to produce pathogenic bioaerosols in the healthcare setting. Hospital privacy curtains have been shown to routinely be contaminated with pathogenic bacteria including other gastrointestinal bacteria that could increase susceptibility to C. difficile infection. PPI medication, which is frequently prescribed in the hospital, has been shown to increase the risk of C. difficile infection, although specific microbiome changes could not be identified.

Ion pumps establish homeostasis across the membranes of living cells. Hearing is a mechanotransduction event that takes place in a closed compartment containing a fluid high in K+ concentrations. In Drosophila melanogaster, this closed compartment is formed by a scolopale cell that wraps around the dendrite of sensory neurons. The receptor lymph is maintained by the scolopale cell. The lumenal membrane of the scolopale cell is the wall of the compartment containing the receptor lymph, the scolopale space. The ablumenal membrane of the scolopale cell creates the border of the scolopidium. The Na/K pump is located on the ablumenal membrane of the scolopale cell, bringing K+ into the scolopale cell cytoplasm and extruding K electrogenically (Roy et al, 2013). We explored other primary and secondary ion pumps that are involved in creating a K+-rich lumen in the Malpighian tubule (Day et al, 2008; Rodan et al, 2012). We used RNAi technology to knockdown one gene at a time and electrophysiology to measure a sound evoked potential (SEP) that reflects the fly’s ability to hear. We found that knocking down V-ATPase, a proton pump, subunits involved in proton extrusion significantly reduces the SEP of knockdown flies. The involvement of cation chloride cotransporters (CCCs) and cation proton antiporter (CPAs), both secondary ion pumps that use the gradients created by the Na/K pump and V-ATPase respectively to pump other ions up their gradient, is less clear. We found that knocking down Nhe3, a CPA, significantly reduced the SEP when knocked down in the scolopale cell, suggesting it as a partner to the V-ATPase. Knocking down CG31547, a CCC, statistically increased the SEP, possibly a type1 statistical error.

Calcium phosphate cements are produced by the mixing of calcium phosphate powders in an aqueous solution resulting in a low-temperature synthesized hydroxyapatite. They have been used as bone substitutes and drug delivery systems. The present work examined the possibility of a machine-based modification to this process to derive a standardized preparation method of calcium phosphate cements that could be loaded with Pantoprazole. To examine the characteristics of these novel materials, the following analyses of hand- and machine-made cements, with and without Pantoprazole were undertaken: in vitro surface characterization, dissolution, hydroxyapatite conversion, Pantoprazole delivery, as well as in vivo reparative bone formation and particulate degradation. The in vitro surface characterization, dissolution at different pHs, and drug release analyses showed insignificant differences between hand- and machine-prepared cements. However, machine-made cements showed increased hydroxyapatite conversion, decreased dissolution at pH 7.4, and better in vivo outcomes than commercially available bone-substitute particulate biomaterials.

Calcium phosphate cements are produced by the mixing of calcium phosphate powders in an aqueous solution resulting in a low-temperature synthesized hydroxyapatite. They have been used as bone substitutes and drug delivery systems. The present work examined the possibility of a machine-based modification to this process to derive a standardized preparation method of calcium phosphate cements that could be loaded with Pantoprazole. To examine the characteristics of these novel materials, the following analyses of hand- and machine-made cements, with and without Pantoprazole were undertaken: in vitro surface characterization, dissolution, hydroxyapatite conversion, Pantoprazole delivery, as well as in vivo reparative bone formation and particulate degradation. The in vitro surface characterization, dissolution at different pHs, and drug release analyses showed insignificant differences between hand- and machine-prepared cements. However, machine-made cements showed increased hydroxyapatite conversion, decreased dissolution at pH 7.4, and better in vivo outcomes than commercially available bone-substitute particulate biomaterials.