Human Growth Hormone ; administration & dosage ; pharmacology ; Recombinant Proteins ; administration & dosage ; pharmacology

No abstract available.
Antiviral Agents/*administration & dosage ; Female ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon-alpha/*administration & dosage ; Male ; Polyethylene Glycols/*administration & dosage ; Recombinant Proteins/administration & dosage ; Ribavirin/*administration & dosage

Methionine-dependent increase in tumor cells is a specific metabolic defect. This metabolic defect is also a target for selective treatment of cancer. Studies found that the methionine gamma-lyase (methioninase, L-methionine gamma-lyase) can specificly split the methionine of extracellular and intracellular, so it can strongly inhibit the growth of tumor cells and induce apoptosis of tumor cells. However, no effect on normal cells has been found, so the methionine gamma-lyase may play the anti-tumor role. We also explored in the present study another effect of methionine gamma-lyase as a single agent on DNA methylation levels and DNA synthesis, which may change as a result of deprivation of methionine, and thus may enhance anti-tumor effects. Animal studies and clinical trials showed that a variety of methionine dependent methionine gamma-lyase can eliminate the tumor cells. Therefore, methionine restriction is an effective anticancer strategy. Methionine gamma-lyase has shown great prospects as a new type of gene therapy. This article made a review of it.
Animals ; Carbon-Sulfur Lyases ; administration & dosage ; Genetic Therapy ; methods ; Humans ; Neoplasms ; drug therapy ; therapy ; Recombinant Proteins ; administration & dosage ; Transfection

Alanine Transaminase ; blood ; Antiviral Agents ; administration & dosage ; Drug Therapy, Combination ; Hepatitis C, Chronic ; blood ; drug therapy ; pathology ; Humans ; Interferon-alpha ; administration & dosage ; Polyethylene Glycols ; administration & dosage ; Recombinant Proteins

OBJECTIVETo investigate the effect of intranasal administration of low dosage recombinant human erythropoietin (r-HuEPO) on seizure in rats.

METHODSAfter intranasal or intraperitoneal administration of r-HuEPO, the behavioral and electroencephalographic changes were observed in pentylenetetrazol (PTZ) and maximal electroshock (MES) induced seizure or electrical amygdaloid-kindled seizure of rats.

RESULTIntranasal administration of low dosage r-HuEPO increased the seizure latency, and decreased the seizure grade and duration, and the number of convulsive episodes in PTZ induced seizure, with the most potential dosage of 2.4 IU. Intraperitoneal administration of r-HuEPO (3 000, 4 000 IU/kg) only decreased the seizure duration and number of convulsive episodes. The seizure grade, forelimb or hindlimb extension duration were decreased in MES-induced seizure by intranasal administration of 2.4 IU r-HuEPO. In addition, intranasal administration of 2.4 IU r-HuEPO decreased the seizure grade, generalized seizure duration and afterdischarge in electrical amygdaloid-kindled rats stimulated with generalized seizure threshold.

CONCLUSIONIntranasal administration of low dosage r-HuEPO can inhibit the seizure in rats.

Administration, Intranasal ; Animals ; Anticonvulsants ; administration & dosage ; Epilepsy ; chemically induced ; drug therapy ; Erythropoietin ; administration & dosage ; Humans ; Male ; Pentylenetetrazole ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins

Female ; Humans ; Interferon-alpha ; administration & dosage ; Lymphomatoid Papulosis ; drug therapy ; pathology ; Mechlorethamine ; administration & dosage ; Middle Aged ; Recombinant Proteins ; administration & dosage ; Solutions

AIMTo investigate the pharmacokinetic characteristics of recombinant human acidic fibroblast growth factor (rhaFGF) after external use in rabbits.

METHODS125I-rhaFGF 180 U.cm-2 was daubed to normal skin and scathed skin in rabbits. The radioactivity and paper chromatography were used to determine the 125I-concentrations and distribution in plasma and organs at different times.

RESULTSThe plasma concentration of 125I-rhaFGF increased rapidily, and reach peak plasma level (73.03 pg.mL-1) thirty minutes after administration. Then the concentration of 125I-rhaFGF decreased quickly after thirty minutes, and approached to zero after three hours. Highest radioactivity accumulated in the skin, followed by kidney, lowest in the brain 96 h after administration.

CONCLUSIONrhaFGF can not be absorbed from the normal skin, whereas a small amount of rhaFGF can be absorbed through scathed skin. The t1/2 of rhaFGF in plasma was very short. Cumulative effect of rhaFGF was not observed. Absorbed rhaFGF showed high affinity to skin, and can be distributed to skin far from the site of administration.

Administration, Cutaneous ; Animals ; Female ; Fibroblast Growth Factor 1 ; administration & dosage ; pharmacokinetics ; Male ; Rabbits ; Recombinant Proteins ; administration & dosage ; pharmacokinetics ; Skin ; injuries ; metabolism ; Skin Absorption ; Tissue Distribution

The chitosan thermosensitive hydrogel is liquid at room temperature but gels rapidly when heated to body temperature. This hydrogel are wildly used for cell encapsulation, drug delivery or tissue-engineered scaffolds. The system can sustain the release of macromolecules over a period of several hours to a few days. However, with low-molecular-weight compounds, the release is generally completed within 24 h. To prepare a functional chitosan thermosensitive hydrogel for slow release both broad-spectrum antibiotic chlorhexidine and growth factor recombined human bone morphogenetic protein-2 (rhBMP-2), The beta-cyclodextrin was used to prepare an inclusion complex with chlorhexidine, and then the latter was incorporated into the chitosan thermosensitive hydrogel system. Simultaneously, rhBMP-2 was added into the hydrogel system. By HAAKE viscosity measuring instrument, we contrasted the viscoelastic properties of system with or without objective factors. And the in vitro release kinetics of chlorhexidine and rhBMP-2 was investigated by HPLC (high performance liquid chromatography) and ELISA (enzyme-linked immunosorbent assay) respectively. The results showed that the addition of chlorhexidine/beta-cyclodextrin inclusion complex to the thermosensitive solution did not change the gelling behavior of the thermosensitive system. Further, the in vitro release profiles demonstrated that the release rate of chlorhexidine and rhBMP-2 from hydrogel became slower, controlled delivery over at least 1 month. By first preparing chlorhexidine/beta-cyclodextrin inclusion complex, and then mixing the IC and rhBMP-2 into the chitosan thermosensitive hydrogel, a functional chitosan thermosensitive hydrogel system with ability of slow release both rhBMP-2 and chlorhexidine is successfully made.
Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; administration & dosage ; Chitosan ; chemistry ; Chlorhexidine ; administration & dosage ; Delayed-Action Preparations ; chemical synthesis ; Drug Carriers ; chemistry ; Drug Combinations ; Hydrogels ; chemistry ; Recombinant Proteins ; administration & dosage ; Temperature ; Transforming Growth Factor beta ; administration & dosage

OBJECTIVESTo compare the efficacy and feasibility between intracoronary and hypodermic injection of granulocyte colony-stimulating factor (G-CSF) on improving cardiac function in a Swine model of chronic myocardial ischemia.

METHODSEighteen Swine underwent placement of ameroid constrictor on left circumflex coronary artery. The presence of myocardial ischemia was verified at four weeks after the operation, and the animals were then randomly assigned into three groups (n = 6 each): (1) administration of vehicle (control), (2) hypodermic injection of G-CSF (5 microgxkg(-1)x;d(-1)) for five days (IH), and (3) intracoronary injection of a bonus G-CSF (60 microg/kg) (IC). Coronary angiogram, cardiac MRI, and (18)F-FDG-SPECT/(99m)Tc-SPECT (DISA-SPECT) measurements were performed at pre-administration and at 4 weeks post administration. Global heart function such as left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVSDV) and left ventricular ejection fraction (LVEF), myocardial perfusion, myocardial viability and myocardial infarct area were evaluated. Myocardial vWF, Bcl-2 and Bax expressions were detected by Western blot and RT-PCR.

RESULTSMRI data showed that left ventricular dilation and dysfunction were similarly prevented in IH and IC G-CSF treated animals at eight weeks after the operation. SPECT revealed that both IH and IC G-CSF equally improved the regional contractility of chronic myocardial ischemia and increased myocardial viability. Myocardial infarct size was also reduced after both G-CSF treatments as detected by MRI. Intracoronary injection of G-CSF did not lead to angiogenesis in other organs. G-CSF treatments were also associated with a significant reduction in myocardial apoptosis and significant increase in angiogenesis.

CONCLUSIONSBoth intracoronary and hypodermic injection of G-CSF were safe and feasible and could equally improve cardiac function and increase angiogenesis in this Swine model of chronic myocardial ischemia.

Animals ; Coronary Vessels ; Disease Models, Animal ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Male ; Myocardial Ischemia ; therapy ; Recombinant Proteins ; Swine

OBJECTIVETo investigate the nasal epithelium toxicity of adjuvants and rHV2 nasal spary(HVS).

METHODCiliary movement were evaluated with in situ toad palate model; The histology assessment of nasal epithelium were carried out after long-lasting and repeated use of HVS.

RESULT AND CONCLUSIONAdjuvants included SDS, Brij 35, azone, lecithin, EDTA, menthol, nipagin and thiomersal were able to significantly inhibited the ciliary movement, while tween80, glycyrrhizic acid monoammonium salt, benzalkonium bromide, sodium benzoate and adhensive materials investigated had less influence on it. HVS was able to damaged the nasal epithelium, but this effect recovered soon after stopping administration. It was demonstrated that SDS, Brij 35, azone,lecithin, EDTA, menthol, nipagin and thiomersal. It had significant cilitoxity, while tween80, glycyrrhizic acid monoammonium salt, benzalkonium bromide, sodium benzoate and adhensive materials investigated had no significance; Chitosan co-administration with some adjuvants may make the cillitoxity severer; It is available that rHV2 be administered by nasal spary.

Adjuvants, Pharmaceutic ; administration & dosage ; toxicity ; Administration, Intranasal ; Animals ; Bufo bufo ; Chitosan ; administration & dosage ; toxicity ; Cilia ; drug effects ; Epithelium ; drug effects ; Female ; Hirudins ; administration & dosage ; toxicity ; Male ; Nasal Mucosa ; drug effects ; Palate ; drug effects ; Rabbits ; Recombinant Proteins ; administration & dosage ; toxicity