Cerebrotendinous xanthomatosis is a rare, inherited lipid-storage disease clinically characterized by tendon xanthoma, progressive neurologic dysfunction(cerebellar ataxia, spinal cord involvement, mental retardation), premature atherosclerosis and cataracts. Substantial elevation of serum cholestanol and urinary bile alcohols with low to normal plasma cholesterol concentrations establishes the diagnosis. Up to now, there have not been any reported case of cerebrotendinous xanthomatosis in Korea. So, we report herein a 36-year-old Korean woman with the clinical features of cerebrotendinous xanthomatosis.
Adult ; Ataxia ; Atherosclerosis ; Cataract ; Cholestanol ; Cholestanols ; Cholesterol ; Diagnosis ; Female ; Humans ; Korea ; Plasma ; Spinal Cord ; Tendons ; Xanthomatosis ; Xanthomatosis, Cerebrotendinous*

OBJECTIVETo investigate the effects of salvianolic acids on human umbilical vein endothelial cells (HUVEC) against damage induced by cholestane-3beta-5alpha-6beta-triol (chol-triol).

METHODSThe viability of HUVEC was measured by MTT method. The apoptosis of HUVEC induced by chol-triol was detected by flow cytometry and TUNEL assay. The production of malondialdehyd (MDA) in HUVEC was tested by thiobarbaturic acid (TBA) assay.

RESULTSThe viability of HUVEC treated with chol-triol 100 micro mol/L decreased by 39.8% while salvianolic acids 100 micro g/ml increased by 27.9%. The apoptotic rate of HUVEC measured by PI staining increased from 6% - 8% to 17% - 20% after chol-triol treatment for 12 h. Salvianolic acids 100 micro g/ml reduced the apoptotic rate to 10% - 14% after treatment HUVEC for 1 h prior to chol-triol treatment. In another experiment, chol-triol increased the number of TUNEL-positive cells 5 times, but salvianolic acids 10 micro g/ml and 100 micro g/ml reduced the number of TUNEL-positive cells by 36.9% and 61.2%, respectively. The production of MDA in HUVEC increased by 120.7% after chol-triol treatment for 12 h. Salvianolic acids 10 micro g/ml and 100 micro g/ml also decreased the concentration of MDA by 28.7% and 39.8%, respectively.

CONCLUSIONSalvianolic acids has protective effect on endothelial cells against damage induced by chol-triol.

Apoptosis ; drug effects ; Benzofurans ; pharmacology ; Caffeic Acids ; pharmacology ; Cell Survival ; drug effects ; Cells, Cultured ; Cholestanols ; toxicity ; Cinnamates ; pharmacology ; Depsides ; Endothelium, Vascular ; cytology ; drug effects ; Humans ; Lactates ; pharmacology ; Malondialdehyde ; metabolism

In recent years, the incidence of infections caused by invasive fungal pathogens has increased dramatically. However, most antifungal agents used in clinic have many drawbacks and cannot meet the demand of the clinical use. Therefore, for the development of new generation of antifungal agents, it is of great significance to find antifungal lead compounds with novel chemical scaffolds and new mode of action. Novel antifungal lead compounds reported in recent years are reviewed. Their chemical structures, antifungal activity and structure-activity relationship are discussed in detail, and current problems and trends in future research are also emphasized.
4-Butyrolactone ; analogs & derivatives ; chemistry ; pharmacology ; Animals ; Antifungal Agents ; chemistry ; pharmacology ; Berberine ; analogs & derivatives ; chemistry ; pharmacology ; Cholestanols ; chemistry ; pharmacology ; Cycloleucine ; analogs & derivatives ; chemistry ; pharmacology ; Fungi ; drug effects ; Heterocyclic Compounds ; chemistry ; pharmacology ; Humans ; Lactones ; chemistry ; pharmacology ; Molecular Structure ; Naphthoquinones ; chemistry ; pharmacology ; Pyridines ; chemistry ; pharmacology ; Structure-Activity Relationship

AIMTo investigate the effect of brassinolide, a plant growth modulator, on multidrug resistance (MDR) of human T lymphoblastoid cell line CCRF-VCR 1000 which was obtained by progressively addition of vincristine (VCR) to sensitive CCRF-CEM cells, and to explore preliminarily the mechanism of reversing action.

METHODSMTT method was used to detect the resistant factor of resistant cell line and the reversing fold after addition of brassinolide. The intracellular accumulation of rhodamine 123, a fluorescent dye transported by P-glycoprotein was detected by flow cytometry, the catalytic activity of topoisomerase II was assessed by Sulliven method to find the effect of brassinolide on resistance. The protein expression of p53 was measured using Western blotting in the sensitive cells and resistant cells to explore the effect of brassinolide.

RESULTSThe resistant factors of CCRF-VCR cells on adriamycin, VP-16 and VCR are respectively as 153.1, 55.9 and 8123.1 folds comparing to the sensitive cell line CCRF-CEM. After treatment of brassinolide under the concentration of 0.001 - 10.0 microg x mL(-1), the resistance of CCRF-VCR was reversed partly with the reversing folds respectively as 4.4 - 11.6. The intracellular accumulation of rhodamine 123 was significantly reduced in the resistant cells. After treatment of brassinolide, the accumulation increased, the level of fluorescent dye was situated between resistant cells and sensitive cells. No alteration of the catalytic activity of topoisomerase II was found among three groups. The level of protein expression of p53 in resistant cells was higher than that of sensitive cells. After brassinolide treatment, the expression of p53 in CCRF-VCR cells restored to the level of sensitive cells.

CONCLUSIONBrassinolide could effectively reverse the resistance of CCRF-VCR cells by inhibiting the effusion of drug transported by P-glucoprotein. To down regulate the abnormal expression of p53 maybe one of the mechanisms of reversing MDR for brassinolide.

Brassica rapa ; chemistry ; Brassinosteroids ; Cell Line, Tumor ; drug effects ; Cholestanols ; isolation & purification ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Humans ; Leukemia, T-Cell ; metabolism ; pathology ; Plant Growth Regulators ; pharmacology ; Pollen ; chemistry ; Steroids, Heterocyclic ; isolation & purification ; pharmacology ; Tumor Suppressor Protein p53 ; metabolism

No abstract available.
Cholestanol ; Spinal Cord* ; Xanthomatosis, Cerebrotendinous*

Cerebrotendinous xanthomatosis(CTX) is a rare familial, autosomal disease which seems to be inherited as a Mendelian recessive. It was first described by van Bogaert et al, in 1937 and only about 30 cases have been reported in the literature. CTX is characterized by tendon xanthomas, bilateral juvenile cataracts, progressive dementia and cerebella ataxia. And deposition of cholestanol appears to be the primary lesion in this disease. We experienced a patient, 43-year-old man who sbowed bilateral cataracts, mold cerebellar dysfunction and multiple xanthomas, the tendinous xanthomatosis was confirmed pathologically and the brain CT scan abnormalities were correlated with neuropathologic findings of CTX. We performed extracapsular cataract extraction on both eyes with a significant improvement in corrected vision.
Adult ; Ataxia ; Brain ; Cataract ; Cataract Extraction ; Cerebellar Diseases ; Cholestanol ; Dementia ; Fungi ; Humans ; Tendons ; Tomography, X-Ray Computed ; Xanthomatosis ; Xanthomatosis, Cerebrotendinous*

Cerebrotendinous xanthomatosis(CTX) is a rare familial, autosomal disease which seems to be inherited as a Mendelian recessive. It was first described by van Bogaert et al, in 1937 and only about 30 cases have been reported in the literature. CTX is characterized by tendon xanthomas, bilateral juvenile cataracts, progressive dementia and cerebella ataxia. And deposition of cholestanol appears to be the primary lesion in this disease. We experienced a patient, 43-year-old man who sbowed bilateral cataracts, mold cerebellar dysfunction and multiple xanthomas, the tendinous xanthomatosis was confirmed pathologically and the brain CT scan abnormalities were correlated with neuropathologic findings of CTX. We performed extracapsular cataract extraction on both eyes with a significant improvement in corrected vision.
Adult ; Ataxia ; Brain ; Cataract ; Cataract Extraction ; Cerebellar Diseases ; Cholestanol ; Dementia ; Fungi ; Humans ; Tendons ; Tomography, X-Ray Computed ; Xanthomatosis ; Xanthomatosis, Cerebrotendinous*

Cerebrotendinous xanthomatosis is a very rare lipid storage disease which is inherited as autosomal recessive trait. The disease is due to an abnormality of cholesterol metabolism, in which excess formation of cholestanol and defect of bile acid synthesis were found. So abnormally high concentration of cholestanol is deposited within the nervous system, the tendons and the other tissues. But, the basic biochemical defect has not as yet been identified. Cerebrotendinous xanthomatosis is characterized by bilateral juvenile cataracts and tendinous xanthomas followed by progressive dementia and cerebellar ataxia. The condition progresses slowly. Death usually occurs during the sixth or seventh decade due to progressive pseudobulbar palsy. The authors have experienced and report a case of presumed cerebrotendinous xanthomatosis in 23-year-old Korean female, and the literatures were reviewed briefly.
Bile ; Cataract ; Cerebellar Ataxia ; Cholestanol ; Cholesterol ; Dementia ; Female ; Humans ; Metabolism ; Nervous System ; Pseudobulbar Palsy ; Tendons ; Xanthomatosis* ; Xanthomatosis, Cerebrotendinous ; Young Adult

Cerebrotendinous Xanthomatosis is a rare inherited autosomal recessive disorder characterized by an increased plasma cholestanol level and the accumulation of sterol in tendon and nervous system. The primary biochemical abnormality is a defect in the synthesis of bile acid due to a lack of hepatic mitochondrial sterol-26-hydroxylase activity. The clinical symptoms usually begin in the 2nd decade and include cataract, xanthoma, and progressive neurological dysfunction. There are variable abnormal findings in the eletrophysiologic and radiologic evaluation. The usual treatment consists of long-term administration of the chenodeoxycholic acid (CDCA or UDCA) or cholic acid, which may correct the biochemical abnormality. We report a case of Cerebrotendinous Xanthomatosis in a 32 year old male patient suffered from gait disturbance and tendon xanthoma in both achilles tendons and left knee area.
Achilles Tendon ; Adult ; Bile ; Cataract ; Chenodeoxycholic Acid ; Cholestanol ; Cholic Acid ; Gait ; Humans ; Knee ; Male ; Nervous System ; Plasma ; Tendons ; Xanthomatosis ; Xanthomatosis, Cerebrotendinous*

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive lipid-storage disease with abnormal deposition of cholesterol and cholestanol in multiple tissues. The disease is caused by mutations in the sterol 27-hydroxylase and characterized by tendon xanthoma, premature cataracts and various neurological manifestations in the central and peripheral nervous systems. A 47-year-old man presented with unsteadiness of gait and weakness on extremities. He had a bilateral cataract extraction at the age of 30 years. Physical examination revealed bilateral elongated mass on Achilles tendons. On neurologic examination, dysarthria, spastic quadriparesis and exaggerated deep tendon reflexes were noted. Surgical excisional biopsy of Achilles tendon revealed a crystalline clefts surrounded by many multinucle-ated giant cells. A moderate degree of cerebral and cerebellar cortical atrophy and focal high signal intensities in sub-cortical white matter were noted on T2-weighted magnetic resonance images. Serum cholestanol was elevated (22 Mg/ml ; normal <2 Mg/ml), while serum cholesterol was normal (186 mg/dl ; normal <250 mg/dl). With clinical, radiologi-cal and biochemical findings, we confirmed a rare case of cerebrotendinous xanthomatosis.
Achilles Tendon ; Atrophy ; Biopsy ; Cataract ; Cataract Extraction ; Cholestanetriol 26-Monooxygenase ; Cholestanol ; Cholesterol ; Crystallins ; Dysarthria ; Extremities ; Gait ; Giant Cells ; Humans ; Middle Aged ; Neurologic Examination ; Neurologic Manifestations ; Peripheral Nervous System ; Physical Examination ; Quadriplegia ; Reflex, Stretch ; Tendons ; Xanthomatosis ; Xanthomatosis, Cerebrotendinous*