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Characterization of Microneedles and Microchannels for Enhanced Transdermal Drug DeliveryPuri, Ashana, Nguyen, Hiep X., Tijani, Akeemat O., Banga, Ajay K. 01 January 2021 (has links)
Microneedle (MN)-based technologies are currently one of the most innovative approaches that are being extensively investigated for transdermal delivery of low molecular weight drugs, biotherapeutic agents and vaccines. Extensive research reports, describing the fabrication and applications of different types of MNs, can be readily found in the literature. Effective characterization tools to evaluate the quality and performance of the MNs as well as for determination of the dimensional and kinetic properties of the microchannels created in the skin, are an essential and critical part of MN-based research. This review paper provides a comprehensive account of all such tools and techniques.
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Neurogenesis Within the Hippocampus After Chronic Methylphenidate ExposureOakes, Hannah V., DeVee, Carley E., Farmer, Brandon, Allen, Serena A., Hall, Alexis N., Ensley, Tucker, Medlock, Kristen, Hanley, Angela, Pond, Brooks B. 14 February 2019 (has links)
Methylphenidate is a psychostimulant used to treat attention deficit hyperactivity disorder. Neurogenesis occurs throughout adulthood within the dentate gyrus of the hippocampus and can be altered by psychoactive medications; however, the impact of methylphenidate on neurogenesis is not fully understood. We investigated the effects of chronic low (1 mg/kg) and high (10 mg/kg) intraperitoneal doses of methylphenidate on neurogenesis in mouse hippocampus following 28 days and 56 days of treatment. Interestingly, methylphenidate, at both doses, increased neurogenesis. However, if methylphenidate treatment was not continued, the newly generated cells did not survive after 28 days. If treatment was continued, the newly generated neurons survived only in the mice receiving low-dose methylphenidate. To investigate the mechanism for this effect, we examined levels of proteins linked to cell proliferation in the hippocampus, including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), tropomyosin receptor kinase B (TrkB), and beta-catenin. BDNF or GDNF levels were not significantly different between groups. However, hippocampal VEGF, TrkB, and beta-catenin were significantly increased in mice receiving low-dose methylphenidate for 28 days compared to controls. Interestingly, high-dose methylphenidate significantly decreased beta-catenin after 28 days and decreased VEGF, beta-catenin, and TrkB after 56 days compared to controls. Thus, low-dose methylphenidate appears to increase cell proliferation and cell survival in the hippocampus, and these effects may be mediated by increase in VEGF, TrkB, and beta-catenin. While high dose methylphenidate may initially increase neuronal proliferation, newly generated neurons are unable to survive long-term, possibly due to decrease in VEGF, TrkB and beta-catenin.
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Exacerbation of Celecoxib-Induced Renal Injury by Concomitant Administration of Misoprostol in RatsCooper, Dustin L., Murrell, Derek E., Conder, Christopher M., Palau, Victoria E., Campbell, Grace E., Lynch, Shaun P., Denham, James W., Hanley, Angela V., Bullins, Kenny W., Panus, Peter C., Singh, Krishna, Harirforoosh, Sam 21 February 2014 (has links)
Nonsteroidal anti-inflammatory drugs (NSAIDs) can produce adverse effects by inhibiting prostaglandin (PG) synthesis. A PGE1 analogue, misoprostol, is often utilized to alleviate NSAID-related gastrointestinal side effects. This study examined the effect of misoprostol on celecoxib renal toxicity. Additionally, the effects of these drugs on cardiovascular parameters were evaluated. Four randomized rat groups were orally gavaged for 9 days, two groups receiving vehicle and two groups receiving misoprostol (100 μg/kg) twice daily. Celecoxib (40 mg/kg) was co-administered once daily to one vehicle and one misoprostol group from days 3 to 9. Urine and blood samples were collected and blood pressure parameters were measured during the study period. Hearts and kidneys were harvested on final day. Day 2 urinary electrolyte samples revealed significant reductions in sodium excretion in misoprostol (0.12±0.05 μmol/min/100 g) and misoprostol+celecoxib groups (0.07±0.02 μmol/min/100 g). At day 3, all treatment groups showed significantly reduced sodium excretion. Potassium excretion diminished significantly in vehicle+celecoxib and misoprostol+celecoxib groups from day 3 onward. Urinary kidney injury molecule-1 levels were significantly increased in vehicle+celecoxib (0.65±0.02 vs. 0.35±0.07 ng/mL, p = 0.0002) and misoprostol+celecoxib (0.61±0.06 vs. 0.37±0.06 ng/mL, p = 0.0015) groups when compared to baseline; while plasma levels of cardiac troponin I increased significantly in vehicle+celecoxib (p = 0.0040) and misoprostol+misoprostol (p = 0.0078) groups when compared to vehicle+vehicle. Blood pressure parameters increased significantly in all misoprostol treated groups. Significant elevation in diastolic (p = 0.0071) and mean blood pressure (p = 0.0153) was noted in misoprostol+celecoxib compared to vehicle+celecoxib. All treatments produced significant tubular dilatation/necrosis compared to control. No significant myocardial changes were noticed; however, three animals presented with pericarditis. Kidney, heart, and plasma celecoxib levels revealed no significant change between vehicle+celecoxib and misoprostol+celecoxib. Concomitant misoprostol administration did not prevent celecoxib renal toxicity, and instead exacerbated renal side effects. Misoprostol did not alter plasma or tissue celecoxib concentrations suggesting no pharmacokinetic interaction between celecoxib and misoprostol.
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Qualitative Analysis of Sequence Specific Binding of Flavones to DNA Using Restriction Endonuclease Activity AssaysDuran, Elizabeth, Ramsauer, Victoria P., Ballester, Maria, Torrenegra, Ruben D., Rodriguez, Oscar E., Winkle, Stephen A. 01 August 2013 (has links)
Flavones, found in nature as secondary plant metabolites, have shown efficacy as anti-cancer agents. We have examined the binding of two flavones, 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8- trimethoxy flavone; FlavA) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H- chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone; FlavB), to phiX174 RF DNA using restriction enzyme activity assays employing the restriction enzymes Alw44, AvaII, BssHII, DraI, MluI, NarI, NciI, NruI, PstI, and XhoI. These enzymes possess differing target and flanking sequences allowing for observation of sequence specificity analysis. Using restriction enzymes that cleave once with a mixture of supercoiled and relaxed DNA substrates provides for observation of topological effects on binding. FlavA and FlavB show differing sequence specificities in their respective binding to phiX. For example, with relaxed DNA, FlavA shows inhibition of cleavage with DraI (reaction site 5′TTTAAA) but not BssHII (5′GCGCGC) while FlavB shows the opposite results. Evidence for tolological specificity is also observed, Molecular modeling and conformational analysis of the flavones suggests that the phenyl ring of FlavB is coplanar with the flavonoid ring while the phenyl ring of FlavA is at an angle relative to the flavonoid ring. This may account for aspects of the observed sequence and topological specificities in the effects on restriction enzyme activity.
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Qualitative Analysis of Sequence Specific Binding of Flavones to DNA Using Restriction Endonuclease Activity AssaysDuran, Elizabeth, Ramsauer, Victoria P., Ballester, Maria, Torrenegra, Ruben D., Rodriguez, Oscar E., Winkle, Stephen A. 01 August 2013 (has links)
Flavones, found in nature as secondary plant metabolites, have shown efficacy as anti-cancer agents. We have examined the binding of two flavones, 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8- trimethoxy flavone; FlavA) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H- chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone; FlavB), to phiX174 RF DNA using restriction enzyme activity assays employing the restriction enzymes Alw44, AvaII, BssHII, DraI, MluI, NarI, NciI, NruI, PstI, and XhoI. These enzymes possess differing target and flanking sequences allowing for observation of sequence specificity analysis. Using restriction enzymes that cleave once with a mixture of supercoiled and relaxed DNA substrates provides for observation of topological effects on binding. FlavA and FlavB show differing sequence specificities in their respective binding to phiX. For example, with relaxed DNA, FlavA shows inhibition of cleavage with DraI (reaction site 5′TTTAAA) but not BssHII (5′GCGCGC) while FlavB shows the opposite results. Evidence for tolological specificity is also observed, Molecular modeling and conformational analysis of the flavones suggests that the phenyl ring of FlavB is coplanar with the flavonoid ring while the phenyl ring of FlavA is at an angle relative to the flavonoid ring. This may account for aspects of the observed sequence and topological specificities in the effects on restriction enzyme activity.
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The Art and Science of ThrivingHagemeier, Nicholas E. 22 May 2019 (has links)
No description available.
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Investigation Of Physicochemical And Formulation Parameters For Transdermal Delivery Of Isoproterenol HC1Patel, Rajesh Arvindkumar 01 January 1987 (has links)
Effects of solubility, partition coefficient, pH and selected adjuvants (propylene glycol and Azone) on the percutaneous penetration of isoproterenol HC1 in vitro have been investigated using human cadaver skin. Preliminary stability studies demonstrated that isoproterenol HC1 was very stable (less than 1% decomposition) for 24 hours at 22(DEGREES) (+OR-) 0.5(DEGREES) in the pH range 1 to 7 in the following solvents: water, normal saline, propylene glycol and a series of propylene glycol-water mixtures (10,20,40 and 60% v/v). The rate of decomposition of the drug in aqueous solutions increased with pH beyond pH 8. In normal saline, the decomposition was significant when the temperature was raised to 37(DEGREES) (+OR-) 0.5(DEGREES). The solubility of isoproterenol HC1 decreased and its skin/vehicle partition coefficient increased with increasing proportions of propylene glycol in the vehicle. Results of the physicochemical and percutaneous penetration studies revealed that 20% v/v propylene glycol in water should be the optimal vehicle for transdermal delivery of isoproterenol HC1. Optimal penetration enhancing effects of AzoneR were seen when incorporated at a concentration of 1% v/v in the 20% v/v propylene glycol-water vehicle and more dramatically when the skin was pretreated with pure Azone for 60 minutes prior to application of the drug formulation. The flux reached a maximum around pH 9 in agreement with the predicted favorable pH environment for neutral forms of isoproterenol HC1. Both neutral and charged forms of isoproterenol HC1 were found to contribute to the total flux in agreement with the proposed model: J = ( Kp . C )ca + ( Kp . C )an + ( Kp . C )n. The calculated permeability coefficients for isoproterenol HC1 were 0.2098 x 10-3, 0.1570 x 10-4 and -0.8665 x 10-3 cm/h for neutral, cationic and anionic species, respectively. Azone enhanced the penetration of all forms of isoproterenol HC1, although the effect was more pronounced on the anionic species. This may be due to facilitation of penetration by formation of an ion-pair between isoproterenol HC1 and Azone. The permeability coefficients for the neutral, cationic and anionic forms of isoproterenol HC1 for penetration through Azone-pretreated skin were 0.8395 x 10-3, 0.1701 x 10-3 and 0.8091 x 10-2 cm/h, respectively.
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Sexual Dimorphism in Aortic Function of UC Davis Type 2 Diabetes Mellitus Rat Model: Estrogen Specific ResponsesAkther, Farjana 01 January 2019 (has links)
Little is known about the interaction between diabetes and sex in vasculature. This study was designed to investigate the effects of estrogen as well as type 2 diabetes (T2D) on aortic function in rats with respect to sex. To test the effects of T2D and sex, UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat model was used. To study the effects of estrogen, ovariectomized Sprague- Dawley female rats and UCD-T2DM rats at pre-diabetic stage were used and the rats were implanted subcutaneously either with placebo or 17 β-estradiol pellets (60 days release, 1.5mg/pellets). The plasma analytes for metabolic parameters and aortic responses to vasodilator and vasoconstrictor agents were determined. The expression of molecules associated with vascular response (e.g. endothelial nitric oxide (NO) synthase (eNOS), Nox1, Nox4, intermediate conductance calcium-dependent potassium channels (IKCa) and small conductance calcium-dependent potassium channels (SKCa)) were also evaluated in aortic tissue.
The main objectives of the study were whether 1) sex differences exist in the development of abnormal vascular responses of UCD-T2DM rats, 2) there were changes in the relative contributions of endothelium-derived relaxing factors (EDRFs) in modulating vascular reactivity of aorta, and 3) estrogen replacement improves the aortic function of ovariectomized UCD-T2DM rats at pre-diabetic stage.
In the study of examining the effect of sex and T2D, diabetes significantly impaired relaxation responses to ACh and SNP in aortic rings from female UCD-T2DM rats, however, potentiated the relaxation in males. The responsiveness to PE was significantly enhanced in both diabetic groups regardless of sex. Accordingly, the basal nitric oxide (NO), as indicated by the potentiation of the response to PE after L-NAME, was reduced in aorta of both diabetic groups. Blocking of COX, sGC and NOS completely abolished the relaxation response in female diabetic group whereas male diabetic animals showed a significant remaining relaxation response to ACh. Further incubation of aortic rings of male animals with TEA or TRAM 34 blunted the relaxation responses to ACh in both control and diabetic groups. However, the inhibitory effects of TEA or TRAM 34 on the ACh-induced relaxation in male UCD-T2DM group was greater than their respective controls. By contrast, ACh responses were not affected following incubation with Apamin in either group of male rats. Moreover, protein expression of IKca were significantly higher in male diabetic group compared with the respective controls.
In the estrogen replacement study, treatment with E2 markedly enhanced the ACh responses of aortic rings in both control and pre-diabetic groups compared to respective placebo treated group. Moreover, effect of E2 in improving the ACh induced relaxation response was significantly higher in control group compared with pre-diabetic animals. The responsiveness to PE were significantly reduced in both E2 treated groups. Basal NO level was significantly higher in both E2 replaced groups but in control group the level was significantly higher than the pre-diabetic rats. Also, protein expression level of Nox1 were decreased in E2 treated control and pre-diabetic group but eNOS were enhanced only in E2 treated control groups.
In conclusion, this study suggests that the effects of type 2 diabetes on aortic ring are sex specific and we showed a differential contribution of EDRFs in male UCD-T2DM rats. Furthermore, our data suggests that elevated eNOS and decreased Nox1protein level may contribute to the higher impact of estrogen in ovariectomized control groups compared to the pre-diabetic rats.
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Evaluation of 10-fold cross validation and prediction error sums of squares statistic for population pharmacokinetic model validationHarite, Shibani 01 January 2003 (has links) (PDF)
It was the objective of the current study to evaluate the ability of 10-fold cross validation and prediction error sum of squares (PRESS) statistic to identify population pharmacokinetic models (PPKM) that were estimated from data without influence observations versus PPKMs from data containing influence observations. The evaluation of 10-fold cross validation and PRESS statistic from Leave-one-out cross-validation for PPK model validation was performed in 3 Phases. In Phase 1 model parameters (theta and clearance) were estimated for datasets with and without influence observations. It was found that influence observations caused an over-estimation of the model parameters.
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Choices, Choices, Choices: Seeking Synergy in Pharm.D. And Ph.D. AdmissionsHagemeier, Nicholas E., Melchert, Russell B., Polovac, Samuel M. 18 July 2019 (has links)
Potential Pharm.D. students and graduate students -- lots of choices! This session targeted by Pharm.D. and graduate admissions stake-holders will describe how understanding career-decision-making processes can assist colleges and schools in developing and implementing interventions to foster Pharm.D. and graduate student recruitment. Attendees will explore mechanisms through which Pharm.D. and graduate programs can collaborate to promote evidence- and experience-informed career decisions among potential matriculants.
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