OBJECTIVETo investigate the effect of polyethylene oxide (PEO) on renal blood flow and its renoprotective effect in rabbits with endotoxin sepsis.

METHODSTwenty normal New Zealand white rabbits were randomly divided into normal saline (NS) group and PEO group (n=10), and endotoxin shock was induced by an intravenous injection of 0.6 mg/kg lipopolysaccharide. Resuscitation was performed when the blood pressure of the rabbits showed a 30% decline, using NS (in NS group) or the mixture of equal volumes of NS and 20 ng/g PEO (in PEO group) perfused at the rate of 5 ml/kg per hour. Before and during shock and at 1 h after resuscitation, the renal hemodynamics was monitored by ultrasound and the venous blood was extracted to examine the renal functions. The heart rate and arterial blood pressure were monitored throughout the experiment.

RESULTSThe rabbits in both groups showed a significantly lower renal artery blood flow velocity during the shock (P<0.05) with significantly increased pulsatility index (PI) and resistance index (RI) compared with those before the shock. One hour after resuscitation, the blood flow velocity in the renal arteries at all levels and the tertiary veins were reduced in NS group without obvious reduction of the PI and RI; in PEO group, the blood flow velocities in the renal arteries increased significantly compared to those before shock (P<0.05), and the PI and RI of the tertiary arteries were significantly lower than those in NS group (P<0.05). In both groups, BUN and Cr increased during endotoxin shock stage, and 1 h after resuscitation, PEO group showed significantly lower BUN and Cr levels than NS group (P<0.05).

CONCLUSIONA small dose of PEO can significantly promote renal perfusion in rabbits with septic shock, thus offering renoprotective effect against early damage in septicopyemia and septic shock.

Animals ; Hemodynamics ; Polyethylene Glycols ; pharmacology ; therapeutic use ; Rabbits ; Renal Circulation ; Shock, Septic ; drug therapy ; physiopathology

The chemotherapy agent L-asparaginase (L-asp) has been an important part of acute lymphoblastic leukemia therapy for over 30 years. It is evident that L-asp has a long-term curative effect. However, L-asp is associated with high incidence of adverse reactions. This has prompted the development of pegylated asparaginase (PEG-asp), which has undergone extensive testing. Apparently, PEG-asp has a prolonged half-life with a better tolerance profile while retaining the antileukemic effect. In this review, we attempt to outline the history of clinical application of L-asp, the pharmacological and clinical potential of various preparations of L-asp, the development of PEG-asp, and the clinical application and adverse events of PEG-asp. The literatures reviewed in this article is collected through online search of the major databases both in English and Chinese.
Antineoplastic Agents ; therapeutic use ; Asparaginase ; adverse effects ; pharmacokinetics ; pharmacology ; therapeutic use ; Blood Coagulation Disorders ; chemically induced ; Humans ; Pancreatitis ; chemically induced ; Polyethylene Glycols ; adverse effects ; pharmacokinetics ; pharmacology ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

BACKGROUND/AIMS: When combined with pegylated interferon alpha-2b (Peg-IFN alpha-2b) for the treatment of genotype 1 chronic hepatitis C (CHC) in Korea, the current guideline for the initial ribavirin (RBV) dose is based on body weight. However, since the mean body weight is lower for Korean patients than for patients in Western countries, current guidelines might result in Korean patients being overdosed with RBV. METHODS: We retrospectively reviewed the medical records of patients with genotype 1 CHC who were treated with Peg-IFN alpha-2b and RBV combination therapy. We divided the patients into groups A (> or =15 mg/kg/day, n=23) and B (<15 mg/kg/day, n=26), given that the standard dose is 15 mg/kg/day. The clinical course in terms of the virologic response, adverse events, and dose modification rate was compared between the two groups after therapy completion. RESULTS: The early response rates (92.0% vs. 83.3%, P=0.634) and sustained virologic response rates (82.6% vs. 73.1%, P=0.506) did not differ significantly between the two groups. During the treatment period, the RBV dose reduction rate was significantly higher in group A than in group B (60.9% vs. 23.1%, P=0.01). CONCLUSIONS: RBV dose reduction is performed frequently when patients are treated according to the current Korean guidelines. Given that lowering the RBV dose did not appear to decrease the virologic response during therapy, reducing RBV doses below the current Korean guideline may be effective for treatment, especially in low-weight patients.
Antiviral Agents/pharmacology/*therapeutic use ; Body Mass Index ; Body Weight ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/drug effects ; Hepatitis C, Chronic/*drug therapy/virology ; Humans ; Interferon-alpha/pharmacology/*therapeutic use ; Male ; Polyethylene Glycols/pharmacology/*therapeutic use ; RNA, Viral/analysis ; Recombinant Proteins/pharmacology/therapeutic use ; Retrospective Studies ; Ribavirin/pharmacology/*therapeutic use ; Sex Factors ; Treatment Outcome

BACKGROUND/AIMS: Lipid profile and insulin resistance (IR) are associated with hepatitis C virus (HCV) and may predict the chronic hepatitis C (CHC) treatment response. The aim of this study was to determine the association between CHC treatment response and lipid profile and IR change during treatment. METHODS: In total, 203 CHC patients were reviewed retrospectively between January 2005 and December 2011 at Soon Chun Hyang University Hospital. The lipid profile, homeostasis model for assessment (HOMA) of IR (HOMA-IR), and HOMA of beta cells (HOMA-beta) were evaluated before interferon plus ribavirin therapy (BTx), at the end of treatment (DTx), and 24 weeks after the end of treatment (ATx). RESULTS: A sustained virologic response (SVR) was achieved by 81% of all patients (49/60), 60% (n=36) of whom possessed genotype 1, with the remainder being non-genotype-1 (40%, n=24). Apart from age, which was significantly higher in the non-SVR group (SVR, 48.0+/-11.2 years, mean+/-SD; non-SVR, 56.6+/-9.9 years; P<0.01), there were no significant differences in the baseline characteristics between the SVR and non-SVR groups. In the SVR group, low density lipoprotein-cholesterol (LDL-C) had significantly changed at DTx and ATx compared to BTx. In addition, HOMA-IR and HOMA-beta were significantly changed at DTx in the SVR group. Among those with a high baseline insulin resistance (HOMA-IR >2.5), HOMA-IR was significantly changed at DTx in the SVR group. CONCLUSIONS: LDL-C appears to be associated with HCV treatment in SVR patients. Furthermore, eradication of HCV may improve whole-body IR and insulin hypersecretion, as well as high baseline insulin resistance (HOMA-IR >2.5).
Adult ; Aged ; Antiviral Agents/pharmacology/*therapeutic use ; Cholesterol/blood ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/genetics ; Hepatitis C, Chronic/*drug therapy ; Humans ; *Insulin Resistance ; Interferon-alpha/pharmacology/*therapeutic use ; Lipid Metabolism/drug effects ; Male ; Middle Aged ; Polyethylene Glycols/pharmacology/*therapeutic use ; Recombinant Proteins/pharmacology/therapeutic use ; Ribavirin/*therapeutic use ; Treatment Outcome ; Triglycerides/blood

OBJECTIVETo investigate the anti-hyperlipidemic effects of apple polyphenols extract (APE) in Triton WR-1339-induced endogenous hyperlipidemic model.

METHODSFirstly, APE was isolated and purified from the pomace of Red Fuji Apple and contents of individual polyphenols in APE were determined using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Secondly, forty male National Institude of Health (NIH) mice were randomly divided into 5 groups with 8 animals in each group. The Fenofibrate Capsules (FC) group and APE groups received oral administration of respective drugs for 7 consecutive days. All mice except those in the normal group were intravenously injected through tail vein with Triton WR-1339 on the 6th day. Serum and livers from all the mice were obtained 18 h after the injection. The changes in serum total cholesterol (TC), triglyceride (TG), lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) were measured by respective kits. Finally, expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) mRNA was measured by real-time reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS SERUM TC AND TG LEVELS SIGNIFICANTLY INCREASED IN TRITON WR-1339-INDUCED MODEL GROUP COMPARED WITH THE NORMAL GROUP (P<0.01). ORAL ADMINISTRATION OF APE [200 AND 400 MG/(KG DAY)] DOSE-DEPENDENTLY REDUCED THE SERUM LEVEL OF TG IN HYPERLIPIDEMIC MICE (P<0.01). SERUM LPL AND HTGL ACTIVITIES SIGNIFICANTLY DECREASED IN TRITON WR-1339-INDUCED MODEL GROUP COMPARED WITH THE NORMAL GROUP (P<0.05). ORAL ADMINISTRATION OF APE [200 AND 400 MG/(KG DAY)] DOSE-DEPENDENTLY ELEVATED THE SERUM ACTIVITY OF LPL IN HYPERLIPIDEMIC MICE (P<0.05 OR P<0.01). FURTHERMORE, COMPARED WITH THE NORMAL GROUP, HEPATIC MRNA LEVEL OF PPARα IN THE MODEL GROUP SIGNIFICANTLY DECREASED (P<0.01). ORAL ADMINISTRATION OF APE [200 AND 400 MG/(KG DAY)] DOSE-DEPENDENTLY ELEVATED THE EXPRESSION OF PPARα IN HYPERLIPIDEMIC MICE (P<0.05 OR P<0.01):

CONCLUSIONAPE could reduce TG level via up-regulation of LPL activity, which provides new evidence to elucidate the anti-hyperlipidemic effects of APE.

Animals ; Chlorogenic Acid ; pharmacology ; therapeutic use ; Cholesterol ; blood ; Flavonoids ; pharmacology ; therapeutic use ; Hyperlipidemias ; blood ; drug therapy ; enzymology ; pathology ; Hypolipidemic Agents ; pharmacology ; Lipoprotein Lipase ; blood ; genetics ; Male ; Mice ; PPAR alpha ; genetics ; metabolism ; Phytotherapy ; Polyethylene Glycols ; RNA, Messenger ; genetics ; metabolism ; Tannins ; pharmacology ; therapeutic use ; Triglycerides ; blood ; Up-Regulation ; drug effects

Epithelial ovarian cancer (OC) is a common gynecologic malignancy in women. The standard treatment for OC is maximal cytoreductive surgical debulking followed by platinum-based chemotherapy. Despite the high response rate to primary therapy, approximately 85% of patients will develop recurrent ovarian cancer (ROC). This review identifies the clinical use of trabectedin in the treatment algorithm for ROC, with specific emphasis on platinum-sensitive ROC, for which trabectedin in combination with pegylated liposomal doxorubicin has been approved as a treatment protocol. The main mechanisms of action of trabectedin at the cellular level and in the tumor microenvironment is also discussed as bases for identifying biomarkers for selecting patients who may largely benefit from trabectedin-based therapies.
Antineoplastic Agents, Alkylating ; therapeutic use ; Clinical Trials as Topic ; DNA Damage ; Dioxoles ; administration & dosage ; pharmacology ; therapeutic use ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Female ; Humans ; Neoplasm Recurrence, Local ; drug therapy ; Neoplasms, Glandular and Epithelial ; drug therapy ; Ovarian Neoplasms ; drug therapy ; Polyethylene Glycols ; administration & dosage ; Tetrahydroisoquinolines ; administration & dosage ; pharmacology ; therapeutic use ; Tumor Microenvironment

OBJECTIVEHuman leukocyte antigen (HLA) haploidentical bone marrow is a potential source of donor to children for its availability. The drawback is deleterious graft versus host disease (GVHD) reaction post transplantation because of the incompatibility of HLA antigen expression between donors and recipients, in which donor T lymphocyte is stimulated to proliferate and differentiate. The methoxy polyethylene glycol (mPEG) is a kind of amphoteric compound without immunogenicity, which was used to modify various proteins covalently and to prepare the versatile blood type. If mPEG modification blocks the activation of T cells in grafts, GVHD reaction probably would become less serious and transplantation might become successful. The aim of this study was to verify the improvement of haploidentical bone marrow transplantation (BMT) in a murine model by using mPEG of certain concentration to modify the grafts.

METHODSMale BALB/c mice were chosen as the donor, and female CB(6)F(1) mice as the recipient. There were three groups of mPEG modification, non-modification and irradiation control, and 20 mice in each group. The modified and non-modified mixture of bone marrow and spleen cells (as T lymphocytes) were transplanted to haploidentical lethally irradiated CB(6)F(1) mice via the tail vein. After the transplant, the hematopoietic recovery, survival rate, acute graft versus host disease (aGVHD) and chromosomal karyotype were analyzed and compared with controls.

RESULTSSeventy-five percent (15/20) of mice survived in the group of mPEG modification, while only 40% (8/20) survived in the group without the modification (chi(2) = 5.01, P = 0.025). And 100% mice died in the group of the irradiation control within 2 weeks. The hematopoietic recovery in the group of mPEG modification was show n to be faster than that in the group without modification (P < 0.05). Histopathological examination of the skin, liver and intestine showed typical signs of aGVHD, but the GVHD grading in the group of modification was less severe. The recipient mice in both groups of transplantation surviving for more than 75 days showed complete donor-type implantation by the chimerism examination.

CONCLUSIONThe modification of grafts by mPEG could alleviate aGVHD and improve the survival rate of mice after the haploidentical bone marrow transplantation.

Animals ; Bone Marrow ; drug effects ; immunology ; Bone Marrow Transplantation ; immunology ; Disease Models, Animal ; Graft Survival ; immunology ; Graft vs Host Disease ; immunology ; prevention & control ; HLA Antigens ; immunology ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Male ; Mice ; Mice, Inbred BALB C ; Polyethylene Glycols ; pharmacology ; therapeutic use ; T-Lymphocytes ; drug effects ; immunology