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91.
The photocytotoxic effect of hypericin (Hyp) targeted by two different delivery techniques, namely, liposomes and anti-hepatocyte
specific antigen (anti-HSA) was investigated. Optical absorption and steady-state fluorescence were used to analyze the conjugation
of Hyp with anti-HSA model and to evaluate the encapsulation capacity and drug release in a liposome model. Particle size
and thermal analysis of the prepared liposomes were performed using laser-light scattering and differential scanning calorimetry
(DSC), respectively. Viability study of HepG2 cells exposed to Hyp in the two delivery systems, in the dark and following
visible light irradiation, was performed in comparison to free Hyp. The intracellular uptake and localization of Hyp in HepG2
cells were analyzed by means of spectrofluorometry and fluorescence microscopy. Spectroscopic measurements demonstrated that
Hyp binds to anti-HSA in its monomeric form. The photocytotoxic effect of Hyp depended clearly on the form of Hyp administered,
either in free form, loaded into liposomes or conjugated with anti-HSA. While liposomes loaded with Hyp (Lip-Hyp) did not
induce significant phototoxicity, both free Hyp or anti-HSA-Hyp inflicted substantial cell mortality, after photoirradiation.
The intracellular uptake of Lip-Hyp by HepG2 cells was estimated to be 20% less compared to free Hyp or anti-HSA-Hyp. In spite
of the equal uptake of both free Hyp and anti-HSA-Hyp, HepG2 cells demonstrated a relatively higher mortality with anti-HSA-Hyp
compared to free Hyp. 相似文献
92.
Maha M. Mahadevan Judy Fleetham Robert B. Church Patrick J. Taylor 《Journal of assisted reproduction and genetics》1986,3(5):304-308
The purpose of this study was to determine if mouse embryos could be grown successfully in a culture medium devoid of the carbon dioxide phase (CO2). Mouse embryos fertilized in vivo were collected and cultured in Hepes medium with and without bicarbonate (HCO3
–) and a phosphate medium with and without HCO3
–. In these experiments no CO2 gas phase was used. Further embryos were cultured in Whittingham's modified Tyrode's (T6) medium with a CO2 gas phase and served as controls. The degree of embryonic development was noted. Surviving blastocysts were transferred to the uteri of pseudopregnant mice and delivery at term was allowed to occur. There was no significant difference in the degree of embryonic development in those embryos cultured in T6 or Hepes medium (+HCO3
–) or in the number of live offspring obtained when these blastocysts were placed within the mouse uterus. Although embryonic development apparently proceeded successfully in the phosphate (+HCO3
–) medium, none of these blastocysts survived when transferred to mouse uteri. No embryonic growth occurred in either the Hepes or phosphate media which were devoid of HCO3
–. It appears that a Hepes medium containing HCO3
–, which uses no CO2 gas phase, is as effective as T6 medium, which uses a gas phase, in supporting in vitro mouse embryonic growth. 相似文献
93.
A. M. Hussein William P. Petros Maureen Ross James J. Vredenburgh Mary Lou Affronti Roy B. Jones Elizabeth J. Shpall Peter Rubin Maha Elkordy Colleen Gilbert Caroline Gupton Merrill J. Egorin J. Soper Andrew Berchuck Daniel Clarke-Pearson Donald A. Berry William P. Peters 《Cancer chemotherapy and pharmacology》1996,37(6):561-568
The purpose of the present study was to determine the maximally tolerated dose of thioTEPA given with fixed high-dose cyclophosphamide
(CPA) and cisplatin (cDDP) followed by autologous bone marrow (ABM) with or without granulocyte colonystimulating factor (G-CSF)-primed
peripheral-blood progenitor cells (PBPCs) in patients with advanced malignancies. Patients were required to have histologically
documented malignancies and adequate renal, hepatic, pulmonary, and cardiac function. CPA was given at 1,875 mg/m2 per day as a 1-h i.v. infusion for 3 consecutive days, and cDDP was given at 55 mg/m2 per day as a 24-h continuous i.v. infusion over 3 days concurrently with CPA. ThioTEPA was given once as a 1-h i.v. infusion
(300–900 mg/m2) either following (the first 13 patients) or prior to CPA and cDDP. In all, 31 patients received PBPCs. A total of 46 patients
were treated. There were 6 deaths among the 15 patients who did not receive PBPCs (13 received thioTEPA following CPA and
cDDP). Among the other 31 patients who received PBPCs (all of whom also received thioTEPA prior to CPA and cDDP), there were
4 deaths, all involving patients with refractory ovarian carcinoma. The main toxicities were mucositis, esophagitis, hepatotoxicity,
and nephrotoxicity. The median time required to achieve an absolute neutrophil count of 500 μl was 10 days (range, 9–12 days)
for those who received PBPCs and 15 days (range, 15–34 days) for those who did not receive PBPCs. Altogether, 47% of the major
organ toxicities (grades 3 and 4 renal, hepatic, and cardiac toxicities) occurred among the 15 patients who did not receive
PBPCs, although these patients received thioTEPA at the lowest 2 dose levels. There were 3 complete responses and 22 partial
responses among 35 evaluable patients (overall response rate, 71%), with the median duration of response being 3.5 months
(range, 2–17 months). The maximally tolerated dose of thioTEPA was 600 mg/m2 given as a 1-h i.v. infusion on the day prior to CPA and cDDP administration. The combination of high-dose CPA, cDDP, and
thioTEPA is a well-tolerated regimen when thioTEPA is given prior to CPA and cDDP and when the combination also includes PBPCs
in addition to ABM. This regimen is active in a variety of malignancies.
Received: 15 February 1995/Accepted: 22 May 1995 相似文献
94.
95.
96.
The development of proteins as therapeutic agents is challenging partly due to their inherent instabilities. Consequently, crystallisation and spray drying techniques were assessed to determine their effects on protein integrity using lysozyme as a model protein. Unprocessed, crystallised and spray-dried lysozyme were characterised by: thermal analysis using hot stage microscopy (HSM), differential scanning calorimetry (DSC), high sensitivity differential scanning calorimetry (HSDSC) and thermogravimetry (TGA); and spectroscopic analysis employing Fourier transform Raman (FT-Raman). Moisture contents were determined by TGA and Karl Fisher titration (KFT). Enzymatic assay measured biological activity. HSM showed no changes in crystals until complete melting. TGA and KFT indicated that spray-dried lysozyme contained a lower moisture content than crystals, hence the higher apparent thermal stability was shown by DSC. HSDSC revealed that crystallisation and spray drying did not affect the denaturation temperature of lysozyme in solution when compared with unprocessed material. However, in the solid state, FT-Raman spectra showed perturbation of the conformational structure of spray-dried sample, whereas crystal conformation remained intact. Enzymatic assay revealed increased activity retention of crystals compared with spray-dried powder. Hence, crystals maintained the conformational integrity and activity of lysozyme in solution. 相似文献
97.
98.
Talaat M el-Oun S Kandeel A Abu-Rabei W Bodenschatz C Lohiniva AL Hallaj Z Mahoney FJ 《Tropical medicine & international health : TM & IH》2003,8(3):234-241
OBJECTIVE: To describe the extent and characteristics of injection use and injection providers in Egypt, given that unsafe injections are associated with blood-borne pathogen transmission. METHODS: Household surveys of a population-based sample of residents in the Nile Delta and in Upper Egypt; focus group discussions and in-depth interviews with community target groups, formal and informal medical providers. RESULTS: Of 4197 persons interviewed, 26.2% reported receiving an injection in the past 3 months. Of these, 77% reported it was for therapeutic indications. The age-sex specific prevalence of injections was highest among children 0-2 years of age and among older adults. Women were more likely to report having an injection than men, particularly at the age above 20 years. Overall, respondents reported receiving on average 4.2 injections per year, indicating that up to 281 million injections are provided per year in Egypt. Injection administrators were public and private sector physicians, pharmacists, barbers, doctor assistants, housekeepers, relatives and friends. Injection prescribers were mostly private and public sector physicians. Of the 1101 respondents who received an injection in the past 3 months, 92 (8.4%) reported that the provider did not use a syringe taken from a closed sealed packet. CONCLUSION: The frequency of therapeutic injection use is high in Egypt and may contribute to blood-borne pathogen transmission. The Ministry of Health and Population (MOHP) is developing interventions targeted towards promotion of injection safety and reduction of injection overuse on community basis as part of a comprehensive strategy to prevent blood-borne pathogen transmission in Egypt. 相似文献
99.
We addressed the host-parasite interplay and the immunopathogenetic events occurring in the central nervous system (CNS) during human African trypanosomiasis. Human first trimester forebrain cells were stimulated with a trypanosome lymphocyte-triggering factor (TLTF) and studied for their immune response as exemplified by cell proliferation and IFN-gamma production. TLTF induced proliferation of human first trimester forebrain cells and IFN-gamma production at the mRNA and protein levels. Astrocytes are the major producers of IFN-gamma in response toTLTE These data illustrated for the first time a direct effect of a parasite factor on human brain cells. TargetingTLTF during the course of the disease may be considered in preventing the deadly neurological complications of human African trypanosomiasis. NeuroReport 相似文献