Clinical trial of cyclosporines produced from two different manufacturers were performed in thirty three renal transplant patients for 16 months divided into 2 phases. A 1:1 conversion on a milligram-to- milligram basis was used for switching from Sandimmune(Sandoz Pharma Ltd, Switzerland) to Implanta(Hanmi Pharma Co, Korea) as the first phase and from Implanta to its microemulsion formulation, Neoplanta, as the second phase. Throughout two phases, the cyclosporine dose, blood pressure and hemoglobin were not changed significantly. Serum creatinine was reduced from the baseline(1.76+/-0.5mg/dL) only during the middle 2 months of the first phase(month 3 : 1.57+/-0.4mg/dL, P<0.05, month 5 : 1.58+/-0.4mg/dL, P<0.05), but it was not changed significantly during the second phase at all. However, blood urea nitrogen(BUN) was increased from baseline throughout the second phase, significantly. Cyclosporine trough level was reduced from baseline(180.87+/-57.5 ng/mL) during the late 3 months of the first phase(month 6 : 131.69+/-61.2ng/mL, P<0.05, month 7 : 137.27+/-82.1ng/mL, P<0.05, month 8 : 135.06+/-58.2ng/mL, P<0.05), while those were increased from baseline to during the early 2 months (month 1 : 172.48+/-64.1ng/mL, P<0.05, month 2 : 170.12+/-49.6ng/mL, P<0.05) and returned to baseline during the remaining 6 months of the second phase. No one developed rejection, but 8 admissions in 7 patients occurred due to cyclosporine nephrotoxicity related elevation of serum creatinine(n=2 in the first phase, n=3 in the second phase), cellulitis in leg(n= 1), partial colectomy for colon cancer(n=1) and reduction of fractured arm(n=1), respectively. Mild abdominal discomfort in 2 patients and nausea with fishy smell on cyclosporine intakes in 3 patients during the early first phase were noted transiently, but no one developed such adverse side effects during the second phase. In conclusion, there were no discernible differences in safety and effectiveness in cyclosporine products from two different manufacturers. Furthermore, the comparable effects between the conventional cyclosporine(Implants) and the microemulsion formulation(Neoplanta) were noted without requiring the dose reduction after the 1:1 conversion.
Blood Pressure ; Cellulitis ; Colectomy ; Colon ; Creatinine ; Cyclosporine* ; Cyclosporins ; Humans ; Kidney Transplantation ; Nausea ; Smell ; Urea

Ulcerative colitis is an idiopathic inflammatory bowel disease characterized by colonic mucosal inflammation and chronic relapsing episodes. The initial therapeutic approach depends on both the extent of colonic involvement and the severity of the disease process at presentation. The mainstay of ulcerative colitis therapy is the administration of 5-aminosalicylic acid (5-ASA) or steroid. Additional medical therapy or colectomy should be considered if the patient remains symptomatic despite conventional therapy, regardless of the extent of colonic involvement. Cyclosporins are effective as a short-term rescue therapy for steroid-refractory ulcerative colitis. Recently, new 5-ASA and steroid formulations with altered delivery, dosing regimens, and less frequent administration have been introduced and demonstrated to be efficacious in active mild to moderate colitis. Infliximab is given to try to avoid the need for colectomy and has proven efficacious in ulcerative colitis. This review outlines the standard therapy for ulcerative colitis and discusses new insights into the recent trend focusing on new therapies, including biological agents and leukocytapheresis.
Antibodies, Monoclonal ; Biological Agents ; Colectomy ; Colitis ; Colitis, Ulcerative ; Colon ; Cyclosporine ; Cyclosporins ; Humans ; Inflammation ; Inflammatory Bowel Diseases ; Leukapheresis ; Mesalamine ; Ulcer ; Infliximab

PURPOSE: The effective management of atopic dermatitis (AD) adjusted to individual clinical courses and demands can be challenging to both patients and physicians. Understanding of actual situations, experienced and perceived by patients with AD and their caregivers, is essential to improve clinical outcomes and satisfaction in real practice. METHODS: This multicenter survey was conducted in patients with AD or their caregivers from 9 centers with questionnaires on diagnosis and management of AD. RESULTS: A total of 324 patients and caregivers participated in the study. Most of the AD cases were initially diagnosed by physicians (80.6%), followed by self-diagnosis. Patients and caregivers thought that allergic substances, such as house dust mites, food, and pollutants, are responsible for AD development; moisturization, environmental control, and improvement of the body constitution are important for AD management. Allergy tests were performed in 194 patients (59.9%), but allergen avoidance strategy was instructed in only 81 subjects (41.8%). Major topical medications were steroids (81.8%) and topical immunomodulators (34.3%), while systemic medications were steroids (42.6%), antihistamines (36.4%), and cyclosporins (2.8%). One hundred eighty-one subjects (55.9%) had received complementary alternative medicine, including Oriental medicine. Many subjects desired to receive individualized management, use of specialized institutions for AD as well as evidence-based, effective, sustainable treatment. CONCLUSION: Our findings suggest that there may still be an unmet need for patients with AD in real practice. Personalized, evidencebased, and multidisciplinary approaches, including patient education, should be implemented for good outcomes.
Body Constitution ; Caregivers ; Complementary Therapies ; Cyclosporine ; Cyclosporins ; Dermatitis, Atopic* ; Diagnosis ; Histamine Antagonists ; Humans ; Hypersensitivity ; Immunologic Factors ; Korea* ; Medicine, East Asian Traditional ; Patient Education as Topic ; Pyroglyphidae ; Steroids

Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is thought to account for more than 80% of primary liver cancers. Both HBV and HCV can establish chronic liver inflammatory infections, altering hepatocyte and liver physiology with potential liver disease progression and HCC development. Cyclophilin A (CypA) has been identified as an essential host factor for the HCV replication by physically interacting with the HCV non structural protein NS5A that in turn interacts with RNA-dependent RNA polymerase NS5B. CypA, a cytosolic binding protein of the immunosuppressive drug cyclosporine A, is overexpressed in many cancer types and often associated with malignant transformation. Therefore, CypA can be a good target for molecular cancer therapy. Because of antiviral activity, the CypA inhibitors have been tested for the treatment of chronic hepatitis C. Nonimmunosuppressive Cyp inhibitors such as NIM811, SCY-635, and Alisporivir have attracted more interests for appropriating CypA for antiviral chemotherapeutic target on HCV infection. This review describes CypA inhibitors as a potential HCC treatment tool that is contrived by their obstructing chronic HCV infection and summarizes roles of CypA in cancer development.
Carcinoma, Hepatocellular* ; Carrier Proteins ; Cyclophilin A* ; Cyclophilins ; Cyclosporine ; Cyclosporins ; Cytosol ; Hepacivirus* ; Hepatitis B virus ; Hepatitis C* ; Hepatitis C, Chronic ; Hepatitis ; Hepatocytes ; Liver ; Liver Diseases ; Liver Neoplasms ; RNA Replicase

OBJECTIVETo explore the efficacy of PSC 833 on multidrug resistance (MDR) reversal and its mechanism.

METHODSHuman erythroleukemic cell line K562 and its doxorubicin-resistant counterpart K562/A02 were used in the study. Cytotoxicity was assessed by MTT assay, P-gp expression by direct immunofluorescence and mdr1 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR) with beta-actin as internal control. Intracellular DNR retention was measured with flow cytometry.

RESULTSK562/A02 cells displayed high levels of mdr1 mRNA and P-glycoprotein and reduced DNR retention compared to their parental K562 cells. 1 micromol/L of PSC 833 had no effect on the levels of mdr1 mRNA and P-gp expression in K562/A02 cells (P > 0.05). PSC 833 conferred a dose-dependent increase on chemosensitivity of K562/A02 to DNR, and its effect was at least 3-fold more potent than that of CsA or Ver. PSC 833 could increase DNR retention in K562/A02 cells. A 100.9% restoration of intracellular DNR retention of the level of K562 cells was gained by PSC 833 at 1.0 micromol/L in K562/A02 cells, whereas only a 86.9% restoration of DNR retention was obtained by CsA at 10 micromol/L in the K562/A02 cells. No effect on DNR sensitivity and retention was found in K562 cells (P > 0.05).

CONCLUSIONPSC 833 is at least 3 approximately 10 fold more potent than CsA or Ver with respect to MDR reversing activity, and it may function by inhibiting the function of P-gp and not reducing the levels of mdr1 mRNA and P-gp directly.

ATP-Binding Cassette, Sub-Family B, Member 1 ; drug effects ; genetics ; metabolism ; Calcium Channel Blockers ; pharmacology ; Cyclosporine ; pharmacology ; Cyclosporins ; pharmacology ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Humans ; K562 Cells ; cytology ; drug effects ; metabolism ; RNA, Messenger ; drug effects ; genetics ; metabolism ; Verapamil ; pharmacology

The injection of streptozotocin(stz) at a high dose (60 mg/kg) into young male rats produces direct beta cell destruction and leads to insulin dependent diabetes (IDD). In contrast the injection of multiple smal doses of stz (40 mg/Kg/d for 5 days) produce IDD, which resembles type l diabetes in man. The provocative effects of the pertussis vaccine (PV) and cyclosporin(CA) against the development of IDD induced by stz were studied. When PV in a dose of 3.75 X 10(10) microorganism was administered to single or multiple stz treated rats, hyperglycemia still developed and persisted during the experiment. No difference was noted in blood glucose levels, but plasma insulin levels were higher in PV treated rats. When CA (10 mg/kg) was administered daily to single or multiple stz treated rats, hyperglycemia seemed to be lower, but this was not statistically significant, however, plasma insulin levels were higher in CA treated rats. The results of this experiment suggest that PV and CA provide some protection to the beta cells of the pancreas.
Animal ; Blood Glucose/metabolism ; Cyclosporins/pharmacology* ; Diabetes Mellitus, Experimental/prevention & control* ; Diabetes Mellitus, Insulin-Dependent/chemically induced ; Male ; Pertussis Vaccine/pharmacology* ; Rats ; Rats, Inbred Strains

To study the effect of P-glycoprotein (P-gp) on the absorption of buagafuran in ileum, the concentration of buagafuran in Caco-2 cells, rat averted intestinal sacs and recirculating perfusion were determined by UV-HPLC method. Verapamil and cyclospirin A (CsA) were used as P-gp inhibitors. The results showed that the transportation of buagafuran across Caco-2 monolayer showed vectorial manner. The permeation of buagafuran from apical (A) to basolateral (B) side was 11% and 24.8% from B to A side. Verapamil and CsA were found to increase the transport of buagafuran by 1.4 and 1.35 fold from A to B side and decrease by 71% and 75% from B to A side, respectively, compared with control. The uptake of buagafuran in Caco-2 cell was also enhanced by P-gp inhibitors, especially in low concentration of buagafuran. Ninety percent of buagafuran was absorbed after 90 min perfusion. Verapamil and CsA were found to improve the absorption of buagafuran at all time points, especially at 30 min (12.4% and 21.5%, respectively). During the incubation, only 14% of buagafuran left in rat averted intestinal sacs, while buagafuran levels were increased in both intestine homogenate and sacs by adding verapamil and CsA. The results indicated that buagafuran was one of the P-gp substrates based on the present study. The absorption of buagafuran can be blocked by P-gp, resulting in the enhancement of buagafuran metabolism in intestine. The poor bioavailability of buagafuran may be partially due to the effect of P-gp on its absorption and transportation in intestinal lumen.
ATP-Binding Cassette, Sub-Family B, Member 1 ; antagonists & inhibitors ; metabolism ; Animals ; Biological Transport ; Caco-2 Cells ; Cyclosporins ; pharmacology ; Humans ; Intestinal Absorption ; drug effects ; Intestine, Small ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Sesquiterpenes ; pharmacokinetics ; Verapamil ; pharmacology

Adult ; Anemia, Aplastic ; drug therapy ; Antilymphocyte Serum ; administration & dosage ; Bone Marrow Transplantation ; Cyclosporins ; administration & dosage ; Drug Therapy, Combination ; Dyskeratosis Congenita ; complications ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents ; administration & dosage ; Male

No abstract available.
Cyclosporine*

No abstract available.
Cyclosporine* ; Dermatomyositis*