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A Large-Scale Process to Produce Microencapsulated Proteins 总被引:2,自引:0,他引:2
Herbert Paul Murphy Keith Johnson OluFunmi Dong Nan Jaworowicz Warren Tracy Mark A. Cleland Jeffrey L. Putney Scott D. 《Pharmaceutical research》1998,15(2):357-361
Pharmaceutical Research - 相似文献
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Jaworowicz DJ Filipowski MT Boje KM 《Journal of chromatography. B, Biomedical sciences and applications》1999,723(1-2):293-299
An improved, validated HPLC assay was developed for the non-steroidal anti-inflammatory agent, nimesulide. In contrast to previous methods, the present assay requires smaller plasma volumes (0.2 ml) and utilizes a commercially available, structurally similar analogue of nimesulide, NS-398. The method involves a liquid-liquid extraction procedure that can be completed within 4 h, followed by reversed-phase HPLC analysis. Briefly, the extraction protocol required toluene extraction of acidified plasma samples, followed by back-extraction of the retained toluene phase with aqueous base. The retained aqueous alkaline phase was concentrated by toluene re-extraction. The retained toluene phase was evaporated to dryness and reconstituted with 100 microl of mobile phase. Extracted samples were injected (50 microl) onto a Shandon Hypersil BDS C18 column (5 microm particle size; 250x4.6 mm) equilibrated with 1.0 ml/min of 68:32 (v/v) methanol-citrate (0.08 M)-phosphate (0.04 M) buffer (pH 3.0) at room temperature, with detection at 240 nm. The chromatographic run time was 12 min with retention times of 5.9 min and 9.1 min for nimesulide and NS-398, respectively. The analytical method was successfully utilized for a pilot pharmacokinetic study. 相似文献
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Smit E Crespo CJ Semba RD Jaworowicz D Vlahov D Ricketts EP Ramirez-Marrero FA Tang AM 《AIDS care》2006,18(8):1040-1045
Physical activity is beneficial for persons with HIV infection but little is known about the relationships between physical activity, HIV treatment and injection drug use (IDU). This study compared physical activity levels between HIV-negative and HIV-positive injection drug users (IDUs) and between HIV-positive participants not on any treatment and participants on highly active antiretroviral therapy (HAART). Anthropometric measurements were obtained and an interviewer-administered modified Paffenbarger physical activity questionnaire was administered to 324 participants in a sub-study of the AIDS Linked to Intravenous Experiences (ALIVE) cohort, an ongoing study of HIV-negative and HIV-positive IDUs. Generalized linear models were used to obtain univariate means and to adjust for confounding (age, gender, employment and recent IDU). Vigorous activity was lower among HAART participants than HIV-positive participants not on treatment (p=0.0025) and somewhat lower than HIV-negative participants (p=0.11). Injection drug use and viral load were not associated with vigorous activity. Energy expenditure in vigorous activity was also lower among HAART participants than both HIV-negative and HIV-positive participants not on treatment. Thus, HIV-positive participants on HAART spend less time on vigorous activity independent of recent IDU. More research is needed into the reasons and mechanism for the lack of vigorous activities, including behavioral, psychological and physiological reasons. 相似文献
4.
Boje KM Jaworowicz D Raybon JJ 《The Journal of pharmacology and experimental therapeutics》2003,304(1):319-325
Nitric oxide (NO) and prostaglandins are inflammatory mediators produced during meningitis. The purpose of the present study was to pharmacologically inhibit cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) to 1) explore the prostaglandin contribution to blood-cerebrospinal fluid barrier permeability alterations and 2) elucidate the in vivo concentration relationship between prostaglandin E2 (PGE2) and NO during experimental meningitis. Intracisternal injection of lipopolysaccharides (LPSs, 200 microg) induced neuroinflammation. Rats were dosed with nimesulide (COX-2 inhibitor), aminoguanidine (iNOS inhibitor), or vehicle. Evans blue was used to assess blood-cerebrospinal fluid barrier permeability. Meningeal NO and cerebrospinal fluid PGE2 were assayed using conventional methods. (Results are expressed as mean +/- S.E.M. of 5-9 rats/group.) Nimesulide failed to prevent blood-cerebrospinal fluid barrier disruption [cerebrospinal fluid Evans blue (micrograms per milliliter): control, 0.22 +/- 0.22*; LPS, 11.58 +/- 0.66; LPS + nimesulide, 10.58 +/- 0.86; *p < 0.05; ANOVA]. Although nimesulide decreased PGE2 (picograms per microliter; p < 0.01) in LPS + nimesulide rats (13.9 +/- 1.96) versus LPS + vehicle (73.8 +/- 12.4), meningeal NO production (picomoles/30 min/10(6) cells; p < 0.01) increased unexpectedly in LPS + nimesulide rats (439 +/- 47) versus LPS + vehicle rats (211 +/- 31). In contrast, aminoguanidine inhibited meningeal NO (picomoles/30 min/10(6) cells; p < 0.005) in LPS + aminoguanidine (111 +/- 20) versus LPS (337 +/- 48) but had no effects (p > 0.05) on PGE2. The in vivo relationship between PGE2 and NO was mathematically described by a biphasic, bell-shaped curve (r2 = 0.42; n = 27 rats; p < 0.0001). Based on these results, inhibition of prostaglandin synthesis not only fails to prevent blood-cerebrospinal fluid barrier disruption during neuroinflammation and but also promotes increased meningeal NO production. The in vivo concentration relationship between PGE2 and NO is biphasic, suggesting that inhibition of COX-2 alone may promote NO toxicity through enhanced NO synthesis. 相似文献
5.
Theodore M. Brasky Yanli Li David J. Jaworowicz Jr. Nancy Potischman Christine B. Ambrosone Alan D. Hutson Jing Nie Peter G. Shields Maurizio Trevisan Carole B. Rudra Stephen B. Edge Jo L. Freudenheim 《Cancer causes & control : CCC》2013,24(9):1675-1685
Breast tissues undergo extensive physiologic changes during pregnancy, which may affect breast carcinogenesis. Gestational hypertension, preeclampsia/eclampsia, gestational diabetes, pregnancy weight gain, and nausea and vomiting (N&V) during pregnancy may be indicative of altered hormonal and metabolic profiles and could impact breast cancer risk. Here, we examined associations between these characteristics of a woman’s pregnancy and her subsequent breast cancer risk. Participants were parous women that were recruited to a population-based case–control study (Western New York Exposures and Breast Cancer Study). Cases (n = 960), aged 35–79 years, had incident, primary, histologically confirmed breast cancer. Controls (n = 1,852) were randomly selected from motor vehicle records (<65 years) or Medicare rolls (≥65 years). Women were queried on their lifetime pregnancy experiences. Multivariable-adjusted logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs). N&V during pregnancy was inversely associated with breast cancer risk. Relative to those who never experienced N&V, ever experiencing N&V was associated with decreased risk (OR 0.69, 95 % CI 0.56–0.84) as were increased N&V severity (p trend < 0.001), longer duration (p trend < 0.01), and larger proportion of affected pregnancies (p trend < 0.0001) among women with ≥3 pregnancies. Associations were stronger for more recent pregnancies (<5 years). Findings did not differ by menopausal status or breast cancer subtype including estrogen receptor and HER2 expression status. Other pregnancy characteristics examined were not associated with risk. We observed strong inverse associations between pregnancy N&V and breast cancer risk. Replication of these findings and exploration of underlying mechanisms could provide important insight into breast cancer etiology and prevention. 相似文献
6.
David J Jaworowicz Jr. Peter J Korytko Sukhwinder Singh Lakhman Kathleen M.K Boje 《Brain research bulletin》1998,46(6):541-546
During meningitis, the host produces a plethora of signaling agents as part of a coordinated defense mechanism against invading pathogens. Nitric oxide (NO) and prostaglandin E2 (PGE2) are two such inflammatory mediators produced in response to bacterial endotoxins. Disruption of the blood–brain barrier (BBB) is one of many pathophysiological consequences of meningitis. The present objective was to examine the time-course of NO and PGE2 production in relationship to BBB permeability alterations during experimentally-induced meningitis. Meningeal inflammation was elicited by intracisternal administration of the bacterial endotoxin, lipopolysaccharides (LPS; 200 μg), and NO, PGE2, and BBB integrity were monitored over the next 24 h. Meningeal NO production was assessed by headspace chemiluminescence; cerebrospinal fluid PGE2 was determined by enzyme-linked immunosorbent assay (ELISA) immunoassay; and BBB integrity was determined by the brain accumulation of 14C-sucrose. Similar time-course profiles for NO and PGE2 were observed, with a peak effect for both inflammatory mediators observed within 6–8 h after intracisternal LPS dosing. Statistically significant (p < 0.05) disruption of the BBB was observed in various brain regions. Strikingly similar temporal relationships were observed for NO and PGE2 production and BBB disruption. These results suggest the hypothesis that NO and PGE2 may act in conjunction to disrupt the BBB during experimental meningitis. 相似文献
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The Stabilization and Encapsulation of Human Growth Hormone into Biodegradable Microspheres 总被引:16,自引:0,他引:16
Johnson OluFunmi L. Jaworowicz Warren Cleland Jeffrey L. Bailey Leonie Charnis Margarita Duenas Eileen Wu Chichih Shepard Douglas Magil Sheila Last Thomas Jones Andrew J. S. Putney Scott D. 《Pharmaceutical research》1997,14(6):730-735
Purpose. To produce and evaluate sustained-acting formulations of recombinant human growth hormone (rhGH) made by a novel microencapsulation process.
Methods. The protein was stabilized by forming an insoluble complex with zinc and encapsulated into microspheres of poly (D,L-lactide co-glycolide) (PLGA) which differed in polymer molecular weight (8–3 1kD), polymer end group, and zinc content. The encapsulation procedure was cryogenic, non-aqueous, and did not utilize surfactants or emulsification. The rhGH extracted from each of these microsphere formulations was analyzed by size-exclusion, ion-exchange and reversed-phase chromatography, SDS-polyacrylamide gel electrophoresis, peptide mapping, and cell proliferation of a cell line expressing the hGH receptor. In addition, the in vivorelease profile was determined after subcutaneous administration of the microspheres to rats and juvenile rhesus monkeys.
Results. Protein and bioactivity analyses of the rhGH extracted from three different microsphere formulations showed that the encapsulated protein was unaltered relative to the protein before encapsulation. In vivo, microsphere administration to rats or monkeys induced elevated levels of serum rhGH for up to one month, more than 20-fold longer than was induced by the same amount of protein injected subcutaneously as a solution. The rate of protein release differed between the three microsphere formulations and was determined by the molecular weight and hydrophobicity of the PLGA. The serum rhGH profile, after three sequential monthly doses of the one formulation examined, was reproducible and showed no dose accumulation.
Conclusions. Using a novel process, rhGH can be stabilized and encapsulated in a solid state into PLGA microspheres and released with unaltered properties at different rates. 相似文献
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