No description available.

No description available.

Adenosine is an important neuromodulator. In the present study, we used mice with expression of human ENT1 (hENT1) and deficiency of CD73, respectively, to address the relative importance of intracellular and extracellular pathways in adenosine regulation. [3H]Nitrobenzylthioinosine binding assays were performed and found increased expression of hENT1 with increased gene dose. We performed a series of behavioural experiments with caffeine and ethanol and compared hENT1 heterozygous and homozygous transgenic mice to their wild type littermates. We found that the expression of hENT1 leads to a change in behavioural responses relative to wild type mice, but no sign of a gene dose dependent increase was observed. With CD73 knockout mice, we performed a series of behavioural experiments with caffeine and ethanol that showed a change in adenosine related behaviours. We also performed experiments that tested anxiety-like behaviours and found reduced anxiety-like behaviours with CD73 knockout mice relative to wild type mice. These studies show that mice with enhanced expression of ENT1 or knockout of CD73 have altered extracellular level of adenosine.

Caffeine has calciuric and osteoclasteogenesis effects. Objectives: To examine the association of caffeine cumulative dose and duration of therapy and the Osteopenia of prematurity (OP) Study design: A retrospective observational cohort study included premature infants less than 31 weeks and birth weight less than 1500 grams. OP was evaluated using chest X-rays on biweekly basis over 12 weeks hospital stay. Caffeine cumulative dose and duration of therapy, steroid dose and diuretic dose along with other maternal and neonatal risk factors were collected to examine their impact on OP. Results: The cohort included 109 infants. 51% had OP and 8% had spontaneous rib fractures. Using the generalized mixed model, Caffeine dose and duration of caffeine displayed strong association with OP. Steroids and vitamin D had significant correlation with OP while diuretic use did not show statistical significant effect. Conclusion: Caffeine cumulative dose and duration of therapy are associated with OP.

Adenosine is an important neuromodulator. In the present study, we used mice with expression of human ENT1 (hENT1) and deficiency of CD73, respectively, to address the relative importance of intracellular and extracellular pathways in adenosine regulation. [3H]Nitrobenzylthioinosine binding assays were performed and found increased expression of hENT1 with increased gene dose. We performed a series of behavioural experiments with caffeine and ethanol and compared hENT1 heterozygous and homozygous transgenic mice to their wild type littermates. We found that the expression of hENT1 leads to a change in behavioural responses relative to wild type mice, but no sign of a gene dose dependent increase was observed. With CD73 knockout mice, we performed a series of behavioural experiments with caffeine and ethanol that showed a change in adenosine related behaviours. We also performed experiments that tested anxiety-like behaviours and found reduced anxiety-like behaviours with CD73 knockout mice relative to wild type mice. These studies show that mice with enhanced expression of ENT1 or knockout of CD73 have altered extracellular level of adenosine.

Cataract is the leading cause of blindness in the world and is defined by opacification of the normally transparent lens of the eye. The major avoidable cause of cataract is ultraviolet radiation (UVR), but no current strategies have been developed to prevent the onset of cataract. Apoptosis and internal and external antioxidant systems that inhibit apoptosis have been shown to play a significant role in cataractogenesis. The main purposes of this thesis were to study the time evolution of apoptosis, to develop the concept of a protection factor (PF), and to investigate the effect of thioltransferase (Grx1) and topical caffeine in UVR cataract development. Further, to elucidate pharmacokinetics and influence on iris diameter of topical caffeine. Sprague Dawley rats were exposed to UVR and TUNEL staining of the lens sections was analysed. Grx1+/+ and Grx1-/- mice were exposed to 5 sub-doses of UVR. Based on the difference of light scattering between Grx1+/+ and Grx1-/- mice, the concept of the PF was developed. Topical caffeine and a placebo were applied to the eyes of separate groups of Sprague Dawley rats that were exposed to sub-doses of UVR and protective effect was evaluated. Penetration of topical caffeine in Sprague Dawley rats to lens and blood was analysed by high performance liquid chromatography. Pupil diameter was measured in groups of unilaterally and bilaterally caffeine-treated ketamine/xylazine anesthetized Sprague Dawley rats. TUNEL-labeling peaked between 5 and 120 hours after UVR exposure. The PF of Grx1 was 1.3. Moreover, topically administered caffeine protected against UVR-induced cataract development with a PF of 1.23. Topical caffeine peaked at 30 min in the lens, increased up to 120 min in the blood and antagonized ketamine/xylazine-induced mydriasis. In conclusion, UVR induces apoptosis, which is evidenced by the peak of TUNEL-labeling at 24 hours after UVR exposure. The PF is an objective relative measure of protective properties that allows the comparison of different antioxidant systems and administered antioxidant substances. Grx1 and caffeine are protective against UVR-induced cataract. Topically administered caffeine penetrates to the lens and inhibits UVR-induced apoptosis. Additionally, a miotic effect of caffeine is described for the first time.

It has been demonstrated that EGCG and caffeine, naturally present in green tea, have thermogenic properties in thermoneutral conditions. The purpose of this study was to quantify the effect of the combined ingestion of EGCG/caffeine on thermogenic responses during a 3h mild cold exposure. Eight healthy males (22± 1 y) were exposed in a randomized, cross over, single blinded fashion to the cold (liquid conditioned suit perfused with 15°C water), after ingesting either a placebo (CON) or an extract of 1600mg of EGCG and 600mg of caffeine (EXP). Thermic, metabolic and electromyographic measurements were monitored at baseline and during cold exposure. After 180min of cold exposure, shivering intensity was significantly reduced by ~32% in EXP condition compared to CON. Area under the curve calculations for total shivering intensity was also reduced by ~21% in EXP (457±99 %MVC.min) compared to CON (361±81 %MVC.min; p=0.007). In contrast, the total area under curve of VO2 was ~25% higher in EXP (33.3±5.5 L O2) compared to CON (25.3±5.1 L O2; p=0.03). Total Heat production (Hprod) also increased by about 11% in the EXP condition (1535±112 kJ) compared to control (1372 ±106 kJ; p=0.002). The decrease in shivering activity combined with an increase in VO2 and Hprod, following the ingestion of EGCG and caffeine in the cold, indicates that nonshivering thermogenesis pathways can be significantly stimulated in adult humans.

This study sought to determine whether caffeine combined with choline could improve short-term memory in healthy adults. The study tested the effect of choline (2 gm) alone and in combination with several concentrations of caffeine (25 mg, 50mg and 100mg) on short-term verbal and visual memory and attention. The Wide Range Assessment of Memory and Learning-2 was utilized. Choline 2 gm + caffeine 25 mg group showed significantly (p<0.05) higher overall memory performance whereas memory performance in the choline 2 gm + caffeine 50 mg group was significantly impaired compared to placebo. The data suggest that specific combinations of caffeine and choline can either facilitate or impair short-term memory in adults with normal cognitive function. Future studies of caffeine and choline combinations will test memory performance in subjects with memory impairment. / Mylan School of Pharmacy and the Graduate School of Pharmaceutical Sciences / Pharmacology / MS / Thesis

Thesis (M.S.)--Florida State University, 2004. / Advisors: Dr. Jeffrey Chanton and Stephen Opsahl, Florida State University, College of Arts and Sciences, Dept. of Oceanography. Title and description from dissertation home page (viewed Jan. 13, 2005). Includes bibliographical references.

Thesis (M.A.)--University of North Carolina at Wilmington, 2004. / Includes bibliographical references (leaves : 46-49).