PURPOSE: It is not clear that the development of glomerular injury and aggravation by tumor necrosis factor alpha (TNF-alpha) is related to intrarenal or serum concentration of TNF-alpha. So, we studied the relationship between the concentration of TNF-alpha and aggravation of glomerular damage in the Henoch-Schonlein nephritis(HSN) and idiopathic nephrotic syndrome(INS). METHODS: We collected the sera and urines of 21 patients with Henoch-Schonlein purpura(HSP) and 22 patients with INS visited Chungbuk National University hospital from March 1998 to March 2001. The concentration of TNF-alpha in the sera and urines were measured by sandwich ELISA. RESULTS: Serum TNF-alpha levels in the HSP patients with renal involvement were significantly higher than those without renal involvement(P=0.009). But urine TNF-alpha levels have no correlation with renal involvement(P=0.088). In the HSN patients, proteinuria have a significant correlation with serum TNF-alpha levels(P=0.004) but less correlation with urine TNF-alpha levels(P=0.053). Otherwise, proteinuria have no correlation with serum TNF-alpha levels(P=0.763) but have a significant correlation with urine TNF-alpha levels(P=0.007) in INS. CONCLUSION: These result suggest that the serum concentration of TNF-alpha would be important to glomerular involvement in HSP. And, it is interesting that proteinuria shows a significant relation with serum TNF-alpha levels in the HSN, but with urine TNF-alpha levels in the INS. This means the major production of TNF-alpha may be originated by extrarenal inflammation in the HSN and by intrarenal tubulo-interstitial damage due to proteinuria in the INS.
Chungcheongbuk-do ; Enzyme-Linked Immunosorbent Assay ; Humans ; Inflammation ; Nephritis* ; Nephrotic Syndrome* ; Proteinuria* ; Tumor Necrosis Factor-alpha*

Apoptosis plays a role in the pathophysiology of many kinds of diseases and in the response of treatment. Compared to the necrosis, the apoptosis is a genetically controlled and energy-dependent process which removes the unwanted cells from the body; programmed cell death or cell suicide. During the apoptosis, phosphatidylserine is expressed in the cytoplasmic outer membrane in the early phase. Annexin V, an endogenous human protein (MW=35 kD), has an affinity of about 10 (-9) M for the phosphatidylserine exposed on the outer membrane of apoptotic cells. Annexin V can be radiolabeled with 99mTc by HYNIC or EC chelators, which can be used as an radiotracer for the in vivo imaging of apoptosis. In this article, we reviewed the apoptosis, radiolabeling of annexin V, and the experimental and clinical data using annexin V imaging.
Annexin A5 ; Apoptosis* ; Cell Death ; Chelating Agents ; Cytoplasm ; Humans ; Membranes ; Necrosis ; Suicide

Botulinum toxins are neurotoxic modular proteins composed of a heavy chain and a light chain connected by a disulfide bond and are produced by Clostridium botulinum. Although lethally toxic, botulinum toxin in low doses is clinically effective in numerous medical conditions, including muscle spasticity, strabismus, hyperactive urinary bladder, excessive sweating, and migraine. Globally, several companies are now producing products containing botulinum toxin for medical and cosmetic purposes, including the reduction of facial wrinkles. To test the efficacy and toxicity of botulinum toxin, animal tests have been solely and widely used, resulting in the inevitable sacrifice of hundreds of animals. Hence, alternative methods are urgently required to replace animals in botulinum toxin testing. Here, the various alternative methods developed to test the toxicity and efficacy of botulinum toxins have been briefly reviewed and future perspectives have been detailed.

Voglibose, an α-glucosidase inhibitor, inhibits breakdown of complex carbohydrates into simple sugar units in intestine. Studies showed that voglibose metabolism in the liver might be negligible due to its poor intestinal absorption. Numerous microorganisms live in intestine and have several roles in metabolism and detoxification of various xenobiotics. Due to the limited information, the possible metabolism of voglibose by intestinal microbiota was investigated in vitro and in vivo.

No abstract available.
Female ; HELLP Syndrome* ; Pregnancy

Effects of diallyl sulfide (DAS) on thioacetamide-induced hepatotoxicity and immunotoxicity were investigated. When male Sprague-Dawley rats were treated orally with 100, 200 and 400 mg/kg of DAS in corn oil for three consecutive days, the activity of cytochrome P450 (CYP) 2E1-selective p-nitrophenol hydroxylase was dose-dependently suppressed. In addition, the activities of CYP 2B-selective benzyloxyresorufin O-debenzylase and pentoxyresorufin O-depentylase were significantly induced by the treatment with DAS. Western immunoblotting analyses also indicated the suppression of CYP 2E1 protein and/or the induction of CYP 2B protein by DAS. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 400 mg/kg of DAS for 3 days, followed by a single intraperitoneal treatment with 100 and 200 mg/kg of thioacetamide in saline for 24 hr. The activities of serum alanine aminotransferase and aspartate aminotransferase significantly elevated by thioacetamide were protected in DAS-pretreated animals. Likewise, the suppressed antibody response to sheep erythrocytes by thioacetamide was protected by DAS pretreatment in female BALB/c mice. Taken together, our present results indicated that thioacetamide might be activated to its toxic metabolite(s) by CYP 2E1, not by CYP 2B, in rats and mice.
Alanine Transaminase ; Animals ; Antibody Formation ; Aspartate Aminotransferases ; Biotransformation ; Blotting, Western ; Corn Oil ; Cytochrome P-450 CYP2E1* ; Cytochrome P-450 Enzyme System ; Erythrocytes ; Female ; Humans ; Male ; Mice ; Rats ; Rats, Sprague-Dawley ; Sheep ; Thioacetamide

Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism.
Animals ; Biological Availability ; Caffeine* ; Cytochrome P-450 CYP1A1 ; Drug Interactions ; Honey ; Humans ; In Vitro Techniques ; Male ; Metabolism ; Microsomes, Liver ; Pharmacokinetics ; Plasma ; Propolis ; Rats* ; Rats, Sprague-Dawley ; Theobromine

Skin is an emerging target tissue in pharmaceutical and cosmetic science. Safety assessment for dermal toxicity is a critical step for development of topically applicable pharmaceutical agents and ingredients in cosmetics. Urgent needs exist to set up toxicity testing methods for dermal safety, and identification of novel biomarkers for pathological cutaneous alteration is highly required. Here we will discuss if vascular endothelial growth factor (VEGF) has a potential as a biomarker for dermal impairment. Experimental and clinical evidences for induction of keratinocytic VEGF under pathological conditions will be reviewed.
Biomarkers ; Skin* ; Toxicity Tests ; Vascular Endothelial Growth Factor A*

PURPOSE: The renal manifestations of tuberous sclerosis complex (TSC) are remarkably diverse, including polycystic kidney disease, simple renal cysts, renal cell carcinomas, and angiomyolipomas. All of these occur in children as well as adults in TSC. Angiomyolipomas, which can cause spontaneous life-threatening hemorrhages, are by far the most prevalent and the greatest source of morbidity. Here, we will address our experience, adding to the literature on pediatric patients with TSC requiring evaluation and treatment for renal manifestations. METHODS: A retrospective analysis was made on 19 patients in whom TSC was diagnosed between May 2001 and Oct. 2005 at Severance Hospital. All patients had clinical diagnoses of TSC as defined by the 1998 tuberous sclerosis complex consensus conference. RESULTS: The patients consisted of 13 boys and 6 girls with a mean age of 7.3 years (range 1 to 22). The renal disease associated with TSC included angiomyolipoma in nine patients (47.4 percent), renal simple cyst in one (5.3 percent), hydronephrosis in one (5.3 percent) patient. Eight patients (42.1 percent) presented with normal kidney contours at abdominal ultrasonography. One patient underwent renal replacement therapy due to chronic renal insufficiency after nephrectomy. Hemorrhage from angiomyolipoma was not detected. CONCLUSION: In our review of 19 cases of TSC, renal manifestations are reported in 57.9 percent of patients. Asymptomatic angiomyolipoma associated with TSC grow gradually, although severe hemorrhages are rare. So patients with TSC should be followed up with serial computerized tomography or abdominal ultrasonography. And also, renal function should be monitored conservatively.
Adult ; Angiomyolipoma ; Carcinoma, Renal Cell ; Child ; Consensus ; Diagnosis ; Female ; Hemorrhage ; Humans ; Hydronephrosis ; Kidney ; Kidney Failure, Chronic ; Nephrectomy ; Polycystic Kidney Diseases ; Renal Insufficiency, Chronic ; Renal Replacement Therapy ; Retrospective Studies ; Tuberous Sclerosis* ; Ultrasonography

OBJECTIVE: To determine the effect of lowering the cutoff values of 3-hour oral glucose tolerance test (OGTT) for gestational diabetes mellitus (GDM). METHODS: Patients with an abnormal 50 gm glucose challenge test (GCT) of more than 130 mg/dL at 24-28 weeks of gestation underwent a 3-hour OGTT at 28-32 weeks of gestation. Patients were divided into four groups according to the criteria recommended by Carpenter-Coustan or National Diabetes Data Group (NDDG) (Control: 50 gm GCT negative [n=268], Borderline: 2 or more abnormal values met or exceeded Carpenter-Coustan criteria but not the NDDG criteria [n=100], NDDG I: 2 or more abnormal values met or exceeded NDDG criteria, [treated, n=70], NDDG II: [not treated, n=42]). Obstetric and perinatal outcomes were analyzed retrospectively. RESULTS: Of 5,827 pregnant women screened for GDM, 112 (1.9%) met the NDDG criteria, whereas 212 (3.6%) met the Carpenter-Coustan criteria. The incidences of poor maternal outcomes were 20.1%, 28.0%, 47.1%, 21.4%, and the incidences of poor neonatal outcomes were 3.7%, 6.0%, 14.3%, 16.7% in the four groups (p<0.05). Multivariable logistic regression analysis showed that 1) NDDG I showed an independent risk factor for poor maternal outcome (OR, 3.37), but the borderline group did not, 2) NDDG I showed an independent risk factor for poor neonatal outcome (OR, 3.87), but the borderline group did not, 3) the borderline group showed an independent risk factor for preterm delivery (OR, 2.67). CONCLUSION: Lowering the cutoff values would increase the number of pregnant women with GDM, while only minimally affecting the perinatal outcomes. Further large-scale prospective studies for Korean pregnant women may be needed.
Diabetes, Gestational* ; Female ; Glucose ; Glucose Tolerance Test ; Humans ; Incidence ; Logistic Models ; Pregnancy ; Pregnant Women ; Retrospective Studies ; Risk Factors