Smith-Lemli-Opitz syndrome (SLOS) is a rare, autosomal recessive disease caused by an inborn error in cholesterol synthesis. Patients with this disease suffer from multiple malformations due to reduced activity of 7-dehydrocholesterol reductase (DHCR7), which increases 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC) concentrations and decreases cholesterol concentration in body fluids and tissue. The SLOS phenotypic spectrum ranges from a mild disorder with behavioral and learning problems to a lethal disease characterized by multiple malformations. Here, we describe a newborn male with ambiguous genitalia who was diagnosed to have type II SLOS during the neonatal period. A clinical examination revealed low levels of unconjugated estriol in the maternal serum, and a variety of fetal ultrasound anomalies, including prenatal growth retardation. After birth, the infant was diagnosed to have congenital heart disease (Tetralogy of Fallot with severe pulmonary artery stenosis), cleft lip and palate, micrognathia, postaxial polydactyly, ambiguous genitalia, and cataracts. Clinical investigation revealed extremely low plasma cholesterol levels and the presence of mutation (homozygote of p.Arg352Gln) in the DHCR7 gene. The patient underwent palliative heart surgery (to widen the pulmonary artery) and received intravenous lipid supplementation. Cholesterol levels increased slightly, but not to normal values. The patient died from cardiopulmonary failure and sepsis 72 days after birth. This report provides the first description of a Korean patient with SLOS confirmed by verification of DHCR7 gene mutation and illustrates the need for early recognition and appropriate diagnosis of this disease.
Body Fluids ; Cataract ; Cholestadienols ; Cholesterol ; Cleft Lip ; Dehydrocholesterols ; Disorders of Sex Development ; Estriol ; Heart Diseases ; Humans ; Infant ; Infant, Newborn ; Learning ; Male ; Oxidoreductases ; Oxidoreductases Acting on CH-CH Group Donors ; Palate ; Parturition ; Plasma ; Polydactyly ; Pulmonary Artery ; Reference Values ; Sepsis ; Smith-Lemli-Opitz Syndrome ; Thoracic Surgery

BACKGROUND/AIMS: Biliary epithelial cells are exposed to highly concentrated oxysterols. Therefore, oxysterols may play a role in pathogenesis of biliary tract diseases. We investigated the cytotoxic effect and apoptosis inducing effect of oxysterol on gallbladder epithelial cells. METHODS: We studied the cytotoxic effect of 3,5- cholestadien-7-one, 5beta-cholestan-3-one and 5,24-cholestadien-3beta-OL which are identified in human bile and pigment gallstones on dog gallbladder epithelial cells (DGBE) and mouse gallbladder epithelial cells (MGBE). We used model bile to dissolve oxysterols as in vitro experiment and also used MTT, cell count, Diff-Quick stain, and flow cytometry to investigate cytotoxicity and apoptosis. RESULTS: Oxysterols dissolved in model bile have cytotoxic effects in a dose dependent fashion. In oxysterol containing model bile, viable cells are 51% in 500 microM 5beta-cholestan-3-one (cholesterol : oxysterol 50:50) and 47% in 5 mM 3,5-cholestadien-7-one (90:10) on MGBE, and are 129% and 38% in 500 microM (50:50) 3,5-cholestadien-7-one and 5beta-cholestan-3-one on DGBE, and are 74% and 71.5% in 5 mM (90:10) 3,5-cholestadien-7-one and 5beta-cholestan-3-one on DGBE, respectively. 500 microM (50:50) 3,5- cholestadien-7-one, 5beta-cholestan-3-one, and 5,24-cholestadien-3beta-OL treated on DGBE increase the apoptotic cell number as 22.0+/-8.8, 30.2+/-12.6, and 45.5+/-13.2%, respectively, compared with control (14.6+/-10.0%). 500 microM (50:50) 3,5-cholestadien-7-one, 5beta-cholestan-3-one, and 5,24-cholestadien-3beta-OL also affect the changes in cell cycles compared with the control. CONCLUSIONS: We concluded that oxysterol containing model bile is useful as an in vitro experiment as model to analyze the effects of oxysterols on biliary epithelial cells and that adequate concentration of oxysterols can induce the cytotoxic effect and the apoptosis on gallbladder epithelial cells.
Animals ; Apoptosis/*drug effects ; Bile/chemistry ; Cholestadienes/*toxicity ; Cholestadienols/*toxicity ; Cholestanes/*toxicity ; Dogs ; Dose-Response Relationship, Drug ; English Abstract ; Epithelial Cells/*drug effects ; Gallbladder/*cytology/drug effects ; In Vitro ; Rats

No abstract available.
Dermatitis, Allergic Contact* ; Fusidic Acid* ; Sodium*

Sodium fusidate, obtained by fermentation of the fungus, Fusidium coccineum, has a steroid structure and shows a very high antitaphycoccal activity. The allergic potentirl of sodium fusidate is low and few cases of contact allergy to sodium fusidate have been reported. We present two cases of allergic contact dermatitis to Fucidin cintentione developed postoperative dressing of a skin biopsy and the other after laser treatment of a vascular nevi. The patch test results showed positive reaction to sodium fusidate in both cases.
Bandages ; Biopsy ; Dermatitis, Allergic Contact* ; Fermentation ; Fungi ; Fusidic Acid* ; Hypersensitivity ; Nevus ; Patch Tests ; Skin ; Sodium*

BACKGROUND: It is traditiqnally considered that the non-bullous fonn of impetigo is primarily of streptococcal origin and the bullous form is of staphylococcal origin. However, recent reports have shown that Staphylococcus aureus (SA) has become the predominant cauative pathogen of non-bullous impetigo as well as of bullous impetigo. Objective. Our purpose was to evaluate the predominant causativi. pathogen, and to establish a therapeutic guideline for impetigo. METHOD: We described the characteristics of lesions and gerformed bacterial culture and susceptibility tests in patients with impetigo. Patients were treatecl by one of three frequently used antibiotics(erythromycin, cefuroxime, fusidic acid). RESULTS: Of 77 patients, there were 47 cases of crusted type(61.9%), 18 cases of mixed type with crusted and bullous lesiona(23.3%), 7 cases of mixed type with crusted and pustular lesions(9.1%) and 5 cases of bullous type(6.6%). SA was grown from 90.1% af the cases, in 83.1% of cases it was the only organism to be foind and no gowth of streptococcus was faund even in mixed infections. An antimicrobial susceptibility test of 63 strains of SA demonstrated high susceptibility to vancomycin(98.4%), cefuroxime(97.1%), oxacillin(96.4%), cephalothin(95.2%), fusidic acid(91.7%) etc, and high resistance to penicillin(93.7%), gentamicin(90.5%), tobramycin(88.9%) and erythromicin(80.9%). Of 19 patients treated with erythrornycin, 12(63.1% ) showed treatment failure at a weeks, while no treatment failure occured in groups treated with cefuroxime and usidic acid. There were statistically significant differences iri therapeutic effect between cefuroxirne and erythromycin(P=0.005 by two tailedy test), and betweer fusidic acid and erythromycin(P=0.0040. But there was no significant difference between cefuroxime and fusidic acid. CONCLUSION: The predominant pathogen of non-bullous impetigo a well as bullous impetigo was SA which were highly resistant to erythromycin and highly sensitive to efuroxime and fusidic acid. In the clinical response, cefuroxinie and fusidic acid treatment were most effective and erythromycin was inadequate for treatment of impetigo.
Cefuroxime ; Coinfection ; Erythromycin ; Furosemide ; Fusidic Acid ; Humans ; Impetigo* ; Staphylococcus aureus ; Streptococcus ; Treatment Failure

BACKGROUND: Skin flap necrosis is a common complication after mastectomy and breast reconstruction. It has been proven that nitroglycerin ointment, as a topical vasodilator, can decrease the rate of skin flap necrosis after mastectomy and breast reconstruction. However, nitroglycerin can cause several side effects, including headache, dizziness, and hypotension. The purpose of this study was to evaluate whether the application of a low dose of nitroglycerin ointment reduced the rate of skin flap necrosis in breast reconstruction after skin-sparing or nipple-sparing mastectomy. METHODS: A total of 73 cases of breast reconstruction after nipple-sparing and skin-sparing mastectomy at our institution from March 2012 to January 2017 were retrospectively studied. Of these patients, 52 received nitroglycerin ointment (4.5 mg) application to the skin around the nipple-areolar complex from August 2015 to January 2017, while 21 received fusidic acid ointment from March 2012 to August 2015. The number of patients who experienced necrosis of the breast skin flap was counted in both groups. RESULTS: Skin flap necrosis developed in 2 (3.8%) patients who were treated with nitroglycerin ointment and 5 (23.8%) patients who did not receive nitroglycerin ointment treatment. Patients who did not receive nitroglycerin ointment treatment had a significantly higher risk of mastectomy skin flap necrosis than patients who did (odds ratio=7.81; 95% confidence interval, 1.38 to 44.23; P=0.02). CONCLUSIONS: Low-dose nitroglycerin ointment administration significantly decreased the rate of skin flap necrosis in patients who underwent breast reconstruction after skin-sparing or nipple-sparing mastectomy, without increasing the incidence of the side effects of nitroglycerin.
Breast* ; Dizziness ; Female ; Fusidic Acid ; Headache ; Humans ; Hypotension ; Incidence ; Mammaplasty* ; Mastectomy* ; Necrosis* ; Nitroglycerin* ; Ointments ; Retrospective Studies ; Skin*

Vibrio vulnificus cytolysin (VVC) has been implicated as one of the important virulence determinants of V. vulnificus that causes serious septicemia and wound infection. An attempt was made to investigate that VVC could act as a ligand which stimulates intracellular signaling systems. Cholesterol dose-dependently blocked VVC hemolytic activity through oli-gomerization of cytolysin. Among cholesterol derivatives including 7-dehydrocholesterol, cholesteryl esters, deoxycholate, and cholestane tested, only 7-dehydrocholesterol induced oligomerization as well as inactivation of VVC. These results show that oligomerization of VVC is completely dependent on three-dimensional structure of cholesterol where specific interaction of cholesterol at oligomerization sites of VVC is very selective. These findings support the idea that cholesterol which constitute many of cellular plasma membrane could be a receptor of VVC on plasma membrane of target cells.
Animals ; Bacterial Toxins/antagonists & inhibitors/chemistry/metabolism ; Cholesterol/chemistry/*pharmacology ; Cytotoxins/antagonists & inhibitors/*chemistry/*metabolism ; Dehydrocholesterols/chemistry/pharmacology ; Dose-Response Relationship, Drug ; Erythrocytes/drug effects ; Hemolysis/drug effects ; Mice ; Molecular Structure ; Signal Transduction ; Substrate Specificity ; Vibrio/*chemistry

The key challenge to generate engineered cells by synthetic biology for producing 7-dehydrocholesterol (7-DHC) in a high titer is the match between functional module and chassis. Our study focused on solving this problem by combining different promoters and yeast chassis to increase 7-DHC production. To optimize the chassis in order to accumulate zymosterol, the substrate for 7-DHC synthesis, we overexpressed truncated HMG-CoA reductase (tHmglp) and squalene epoxidase (Erglp), both are key genes of yeast endogenous zymosterol biosynthetic pathway. In addition, we knocked out C-24 methyl transferase (Erg6p) and C-22 dehydrogenase (Erg5p) to inhibit the conversion of zymosterol to ergosterol. By introducing heterologous C-24 reductase under three promoters with different strengths, namely TDH3p, PGK1p and TDH1p, we constructed functional modules of diverse activities. Nine engineeredcells were generated based on the combination of these three modules and three chassis. The result shows that the engineered cell composed of functional module regulated by TDH3p and chassis SyBE_000956 had the highest 7-DHC production, indicating a better match than others. This study provides evidences for importance of match and empirical support for rational design of subsequent researches.
Cholesterol ; metabolism ; Cytochrome P-450 Enzyme System ; genetics ; Dehydrocholesterols ; metabolism ; Gene Knockout Techniques ; Hydroxymethylglutaryl CoA Reductases ; metabolism ; Industrial Microbiology ; Methyltransferases ; genetics ; Promoter Regions, Genetic ; Saccharomyces cerevisiae ; genetics ; metabolism ; Saccharomyces cerevisiae Proteins ; genetics ; Synthetic Biology

Vitamin D is present in two forms, ergocalciferol (vitamin D2) produced by plants and cholecalciferol (vitamin D3) produced by animal tissues or by the action of ultraviolet light on 7-dehydrocholesterol in human skin. Both forms of vitamin D are biologically inactive pro-hormones that must undergo sequential hydroxylations in the liver and the kidney before they can bind to and activate the vitamin D receptor. The hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D], plays an essential role in calcium and phosphate metabolism, bone growth, and cellular differentiation. Renal synthesis of 1,25(OH)2D from its endogenous precursor, 25-hydroxyvitamin D (25OHD), is the rate-limiting and is catalyzed by the 1alpha-hydroxylase. Vitamin D dependent rickets type I (VDDR-I), also referred to as vitamin D 1alpha-hydroxylase deficiency or pseudovitamin D deficiency rickets, is an autosomal recessive disorder characterized clinically by hypotonia, muscle weakness, growth failure, hypocalcemic seizures in early infancy, and radiographic findings of rickets. Characteristic laboratory features are hypocalcemia, increased serum concentrations of parathyroid hormone (PTH), and low or undetectable serum concentrations of 1,25(OH)2D despite normal or increased concentrations of 25OHD. Recent advances have showed in the cloning of the human 1alpha-hydroxylase and revealed mutations in its gene that cause VDDR-I. This review presents the biology of vitamin D, and 1alpha-hydroxylase mutations with clinical findings.
Animals ; Biology ; Bone Development ; Calcitriol ; Calcium ; Cholecalciferol ; Clone Cells ; Cloning, Organism ; Dehydrocholesterols ; Ergocalciferols ; Humans ; Hydroxylation ; Hypocalcemia ; Kidney ; Liver ; Muscle Hypotonia ; Parathyroid Hormone ; Receptors, Calcitriol ; Rickets ; Seizures ; Skin ; Ultraviolet Rays ; Vitamin D ; Vitamins

BACKGROUND: A small subset of adolescents atopic dermatitis (AD) tends to persist. This also leads to get more antibiotics exposure with advancing years. Antibiotic resistance has been regarded as a serious problem during Staphylococcus aureus treatment, especially methicillin-resistant S. aureus (MRSA). OBJECTIVE: It was investigated the S. aureus colonization frequency in the skin lesions and anterior nares of adolescent AD patients and evaluated the changes in S. aureus antimicrobial susceptibility for years. METHODS: Patients who visited our clinic from September 2003 to August 2005 were classified into group A, and patients who visited from August 2010 to March 2012 were classified into group B. To investigate the differences with regard to patients' age and disease duration, the patients were subdivided into groups according to age. Lesional and nasal specimens were examined. RESULTS: Among the 295 AD patients, the total S. aureus colonization rate in skin lesions was 66.9% (95/142) for group A and 78.4% (120/153) for group B. No significant changes in the systemic antimicrobial susceptibilities of S. aureus strains isolated from adolescent AD patients were observed during about 10-year period. The increased trend of MRSA isolation in recent adolescent AD outpatients suggest that the community including school could be the source of S. aureus antibiotic resistance and higher fusidic acid resistance rates provides evidence of imprudent topical use. CONCLUSION: Relatively high MRSA isolation and fusidic acid resistance rates in recent AD patients suggest that the community harbors antibiotic-resistant S. aureus.
Adolescent ; Anti-Bacterial Agents ; Colon ; Dermatitis, Atopic* ; Drug Resistance, Microbial ; Fusidic Acid ; Humans ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Outpatients ; Skin ; Staphylococcus aureus* ; Staphylococcus*