Efficacy, safety, and potential industry bias in using deoxycholic acid for submental fat reduction - A systematic review and meta-analysis of randomized clinical trials

Abstract Lipolytic substance injections to reduce localized fat have been extensively used because it is a low-invasive method. This review aimed to evaluate the efficacy and safety of deoxycholic acid in submental fat reduction compared to a placebo and investigate the potential industry sponsorship bias in the results of randomized clinical trials on this topic. Ten electronic databases were extensively searched for randomized clinical trials without restriction on language and year of publication. Two reviewers extracted the data and assessed the individual risk of bias in the studies with the RoB 2.0 tool. The industry sponsorship bias was evaluated according to citations in the articles regarding industry funding/sponsorship throughout the texts. Fixed and random effects meta-analyses were performed, and the results were reported in Risk Ratio (RR) at a 95% Confidence Interval (95% CI). The initial search provided 5756 results, of which only five were included. Only two studies had a low risk of bias. All studies showed a potential industry bias. The meta-analysis showed that patients treated with deoxycholic acid had significant positive results for all efficacy outcomes and a higher risk of fibrosis, pain, erythema, numbness, swelling, edema, pruritus, nodules, headache, and paresthesia. The low to moderate certainty of evidence found allows concluding that deoxycholic acid is effective in submental fat reduction, causing well-tolerated adverse effects. However, all eligible studies showed a potential industry bias.

Adverse Drug Reactions to Antifungals Used in the Management of COVID-19 Associated Rhino-Orbito-Cerebral Mucormycosis

Objectives: To determine the incidence and frequency of adverse drug reactions (ADRs) to find out factors, if any contributing to the same, while also exploring the use of amphotericin B deoxycholate as a cheaper and safe alternative to liposomal amphotericin B. Materials and Methods: It was a cross-sectional observational study, with a study population of 50 conducted over three months after ethics approval. All adult patients admitted to a tertiary care center, in a metropolitan city of Maharashtra, diagnosed with Rhino-orbito-cerebral mucormycosis, with a history of previous COVID-19 infection and receiving antifungals for the treatment of the same were included in the study. Central Drugs Standard Control Organization (CDSCO) ADR reporting forms were used to collect data. Results: Electrolyte disturbances mainly hypokalemia were the most frequently encountered ADR with both Amphotericin formulations (39/50; 20.31%) followed by pain at the injection site (33/50; 17.19%). Nephrotoxicity occurred slightly more frequently with Amphotericin B Deoxycholate (19/29; 65%), compared to Liposomal Amphotericin B (11/19; 57%), while Posaconazole was mainly associated with gastrointestinal (GI) disturbances and hepatotoxicity. Conclusion: Amphotericin B Deoxycholate was associated most with ADRs, hypokalemia, and pain at the injection site being the most frequent. However, concerning nephrotoxicity, both Amphotericin formulations showed only a modest difference. Posaconazole was associated with the least number of ADRs and had a favorable safety profile.

Bile salt induced solubilization of methylene blue:Study on methylene blue fluorescence properties and molecular mechanics calculation / 药物分析学报

Methylene blue (MB) is a hydrophobic drug molecule, having importance both as a staining reagent and pharmaceutical agent. MB is strongly fluorescent, with an emission peak at 686 nm (λex 665 nm). In the study, the possibility of MB as an extrinsic fluorophore to study the micellization behavior of bile salts (BSs) was carried out. Since BSs are drug delivery systems, the solubilization of hydrophobic MB drug molecule by BSs was achieved and the nature of association of MB with BS media, namely sodium cholate (NaC) and sodium deoxycholate (NaDC) was evaluated. Change in the photophysical properties of MB is monitored through fluorescence intensity and fluorescence anisotropy at emission peak, 686 nm of MB. Molecular mechanics calculations were carried out to evaluate the MB–BS association. The estimated heat of formation,ΔHf values are–625.19 kcal/mol for MB–NaC and–757.48 kcal/mol for MB–NaDC. The photophysical study also revealed that MB reports the step-wise aggregation pattern of BSs media, as an extrinsic fluorescence probe.

Uso de injeções lipolíticas com desoxicolato de sódio em depósitos de gordura: contexto histórico e atual / Lipolysis injections with sodium deoxycholate: historical and current context

Desde a primeira publicação a respeito, em 2001, a aplicação de injeções lipolíticas para gordura localizada tornou-se um procedimento amplamente utilizado na clínica. Consiste de múltiplas injeções subcutâneas de compostos lipolíticos, que podem ter diversos mecanismos de ação. O fármaco mais utilizado atualmente, o desoxicolato de sódio, foi descoberto por acaso, em uma associação com fosfatidilcolina em que sua única função era de veículo da fórmula. Conforme estudos foram sendo realizados, concluiu-se que a ação no tecido era devido ao desoxicolato, um sal biliar que emulsiona os lipídios da membrana celular, resultando em lise do adipócito e consequente necrose do tecido adiposo. Seus principais efeitos adversos, muito frequentemente relatados, incluem dor intensa, edema e formação de nódulos fibrosos nos pontos aplicados. Em decorrência de falhas na aplicação, alguns efeitos adversos mais graves podem ocorrer, como injúria do nervo facial e infecções persistentes. Apesar destes, a utilização de desoxicolato de sódio na camada subcutânea apresenta resultados muito positivos, como publicado em diversos ensaios clínicos, inclusive com relação à satisfação do paciente perante o desfecho final, sendo, portanto, uma boa escolha de técnica para contorno corporal e diminuição de depósitos de gordura localizados. (AU)

Since the first paper, in 2001, injection lipolysis for localized fat deposits became a widely used procedure in the clinics. It consists basically of multiple subcutaneous injections of lipolytic compounds, with many different mechanisms of action. The most used drug nowadays is sodium deoxycholate, initially thought to be only the solubilizing vehicle in the phosphatidilcholine formula. As studies were performed, it was concluded that the changes seen in the tissue was due to sodium deoxycholate, a biliary salt which emulsifies membrane lipids, resulting in adipocyte lysis and consequent adipose tissue necrosis. Its main adverse events include pain, oedema and fibrous nodules. Due to poor technique, more serious adverse events may happen, such as nerve injury or persistent infection by mycobacterium. In spite of these, the use of sodium deoxycholate presents great results, as published in many clinical trials, including patient's satisfaction at the end of the treatment, which is of much value in the aesthetics field. Therefore, mesotherapy using sodium deoxycholate is a good choice for body contouring and localized fat deposits. (AU)

Recuperación y diferenciación de aeromonas con CromoCen AE y CromoCen AGN / Recovery and differentiation of Aeromonas with CromoCen AE and CromoCen AGN

INTRODUCCIÓN: en la actualidad las especies del género Aeromonas han emergido como un problema de salud pública, son ellas los agentes etiológicos de las enfermedades diarreicas con el aumento de la atención médica por años. Los procedimientos convencionales para su diagnóstico son muy engorrosos, laboriosos y duraderos. Una nueva metodología que emplea medios de cultivo cromogénicos ha permitido la simplificación y aceleración de su diagnóstico, que ofrece resultados altamente específicos. OBJETIVO: estudiar el efecto de la combinación de diferentes agentes selectivos de los microorganismos grampositivos sobre el aumento de la capacidad de recuperación, cuantificación y diferenciación de las especies de Aeromonas. MÉTODOS: se estudió el efecto inhibidor de la combinación de agentes selectivos (desoxicolato de sodio (0,05-0,2 g·L-1), sales biliares (0,65 g·L-1), verde brillante (0,025-0,03 g·L-1), cristal violeta (0,001-0,01 g·L-1) y sulfito de sodio (0,8 g·L-1) sobre los microorganismos grampositivos, así como la capacidad de recuperación, cuantificación y diferenciación de las especies de Aeromonas. Como base se utilizó la formulación de CromoCen AGN, sin el desoxicolato de sodio. RESULTADOS: los valores de las productividades de los medios CromoCen AE y CromoCen AGN a partir del inóculo 1,5 × 102 UFC·mL-1 resultaron, para: A. hydrophila 116,8 % y 23,9 %, A. caviae 100,8 % y 3,95 %, A. bestiarium 93,6 % y 28,8 %, A. culicicola 85,1 % y 66,12 %, A. veronii 116,7 % y 59,2 %, A. popoffi 86,56 % y 13,2 %, A. trota 94,8 % y 11,25 % y para A. eucrinophila 103,9 % y 2,80 %. La nueva composición cromogénica logró la diferenciación de los microorganismos por sus características culturales: color, forma, superficie, bordes en las colonias y proteólisis del medio circundante. CONCLUSIONES: la combinación de diferentes agentes selectivos para la inhibición de los microorganismos grampositivos coadyuvo el aumento de la capacidad de recuperación, cuantificación y diferenciación de las especies de Aeromonas.

INTRODUCTION: Species of the genus Aeromonas are a current public health problem, for they are the etiological agents responsible for the growing incidence of diarrheal diseases requiring medical care. Conventional procedures for their diagnosis are very complicated, laborious and time-consuming. A new methodology based on the use of chromogenic culture media allows diagnostic simplification and acceleration, yielding highly specific results. OBJECTIVE: Study the effect of combining several selective agents for gram-positive microorganisms upon an increased capacity for recovery, quantification and differentiation of Aeromonas species. METHODS: Assessment was conducted of the inhibiting effect of combined selective agents (sodium deoxycholate (0.05-0.2 g·L-1), bile salts (0.65 g·L-1), brilliant green (0.025-0.03 g·L-1), crystal violet (0.001-0.01 g·L-1) and sodium sulfite (0.8 g·L-1)) on gram-positive microorganisms, as well as their capacity for recovery, quantification and differentiation of Aeromonas species. The base used was the CromoGen AGN formulation without sodium deoxycholate. RESULTS: Productivity values for the media CromoCen AE and CromoCen AGN based on inoculation of 1.5 × 102 CFU·mL-1 were 116.8 % and 23.9 % for A. hydrophila, 100.8 % and 3.95 % for A. caviae, 93.6 % and 28.8 % for A. bestiarium, 85.1 % and 66.12 % for A. culicicola, 116.7 % and 59.2 % for A. veronii, 86.56 % and 13.2 % for A. popoffi, 94.8 % and 11.25 % for A. trota, and 103.9 % and 2.8 0% for A. eucrinophila. The new chromogenic composition enabled differentiation of microorganisms based on their cultural characteristics: color, shape, surface, colony borders and environmental proteolysis. CONCLUSIONS: Combination of various selective agents for the inhibition of grampositive microorganisms led to an increased capacity for recovery, quantification and differentiation of Aeromonas species.

Determination of Cholic Acid,Hyodeoxycholic Acid and Deoxycholate Acid in Naoxueshuan Tablet by HPLC-ELSD / 中国药房

OBJECTIVE:To establish a method for the contents determination of cholic acid,hyodeoxycholic acid and deoxy-cholate acid in Naoxueshuan tablet. METHODS:HPLC-ELSD was performed on the column of SHIMADZU VP-ODS C18 with mo-bile phase of acetonitrile-0.2% formic acid(gradient elution)column temperature was 30 ℃,at flow rate of 1.0 ml/min,and the vol-ume injection was 10 μl. RESULTS:The linear range was 0.039 84-0.398 4 mg for cholic acid,0.032 064-0.320 64 mg for hyode-oxycholic acid and 0.0339 52-0.339 52 μg for deoxycholate acid(r≥0.999 0),and the logarithm value of volume injection and peak area showed good linear relationship;RSDs of precision,stability and reproducibility tests were lower than 2%;recoveries were 101.33%-104.05%(RSD=0.95%,n=6),95.56%-101.38%(RSD=2.54%,n=6)and 96.07%-97.12%(RSD=0.44%,n=6),re-spectively. CONCLUSIONS:The method is simple and accurate,and suitable for the contents determination of cholic acid,hyode-oxycholic acid and deoxycholate acid in Naoxueshuan tablet.

Prurigo Pigmentosa after Injection Lypolysis with Phosphatidylcholine and Deoxycholate / 대한피부과학회지

No abstract available.

Determination of percutaneous absorption characteristics of Panax notoginseng saponins transfersomes by in vitro skin permeation method / 中草药

Objective: To establish the key conditions for the determination of percutaneous absorption of Panax notoginseng saponins (PNS) in transfersomes (TFS) by in vitro skin permeation method and clarify its percutaneous absorption characteristics. Methods: The film hydration-dispersion method was used to prepare PNS TFS and liposomes (LPS). Their physico-chemical properties were characterized. The drug content and sample volume of PNS TFS for in vitro skin permeation experiments were screened. The effects of vesicle type (TFS or LPS), size of the TFS, and formulation amount of sodium deoxycholate (DOC) on percutaneous permeation of PNS were investigated. Results: The TFS and LPS were mainly unilamellar vesicles with roundish shape and size of (121.2 ± 4.5) and (113.9 ± 2.9) nm, without gathering property. According to the cumulative permeated quantity (Qn) and steady-state percutaneous permeation rate (J) of the assayed ingredients, the appropriate PNS content in the TFS was 500 mg and sample volume was 0.5 mL. Compared with those of the LPS, the Qn values of each assayed component (ginseng saponin Rg1, ginseng saponin Rb1, ginseng saponin Re, PNS R1) in PNS of the TFS were high, and the J values of the assayed components in TFS were about 2-3 times of those in the LPS. The Qn and J values of the assayed components in the TFS with an average size of 120 nm were obviously higher than those of the assayed components in the TFS with an average size of 250 nm. The Qn and J values of the assayed components in PNS TFS with large amount of DOC were prominently higher than those containing small amount of DOC, and the increase ratios of different assayed components were different. Conclusion: In vitro skin permeation method is suitable for the determination of percutaneous absorption of PNS in TFS. The TFS promote drug percutaneous permeation stronger than the LPS and the promotion increases with an appropriate increase of the amount of DOC and decrease of vesicle size of the TFS.

Comparison of efficacy and safety among three injections of fat soluble drugs on fat dissolution / 中华医学美学美容杂志

Objective To investigate the efficacy and safety of three injections fat soluble drugs to dissolve fat.Methods 3T3-L1 preadipocytes were treated with 5％ phosphatidyl choline (PC),4.5％ deoxycholate salts (DC) and lipostabil,respectively; thiazolyl tetrazolium (MTT) method was used to measure the different fat cell proliferation activity,the enzyme assay to measure liquid triglyceride (TG) content in culture media and to evaluate the degree of dissolution of the fat cells.16 Hartley white guinea pigs were randomly divided into four groups:shoulder (group a),scapular region (group b),hips (group c),and back (control group) were injected with fat soluble drug 0.5 ml in different parts of the guinea pig fat layer,and at different time points tissues were cut for pathological analysis.Results The proliferative activity of 3T3-L1 preadipocytes were significantly decreased after treatment with three types of fat soluble drugs compared with control group (P＜0.05),and their effects on dissolution of fat cells were also significant:the contents were 5％ PC (4.14±0.92)mmol/L,4.5％ DC (3.91 ±0.67) mmol/L,and lipostabil (4.23± 0.76) mmol/L,respectively,which were significantly higher than that of the control (1.91±0.12) mmol/L (P＜0.05); guinea pigs in vivo showed that the three types of fat soluble drugs on dissolving adipose tissue at the injection site had varying degrees of swelling,lymphocytic infiltration,and fat cell degeneration,fusion and decrease in number.Conclusions Three fat soluble injections could dissolve the fat cells in some degree,in whichi lipostabil is stronger than other fat soluble drugs,but their effect on adipose tissue is nonspecific,and therefore clinical application of those fat soluble drugs should be in high caution.

Study on preparation and in vitro transdermal penetration of betulinic acid ethosomes modified by sodium deoxycholate / 中草药

Objective: To prepare and optimize the prescription of betulinic acid (BA) ethosomes modified by sodium deoxycholate (SDC) and then to investigate its transdermal penetration as carrier of BA. Methods: The BA ethosomes modified by SDC were prepared by the ethanol injection method. The encapsulation efficiency (EE) was considered as the evaluation index to optimize the prescription of the ethosomes by orthogonal design, and the shape and particle size of the optimized ethosomes were analyzed. The in vitro transdermal absorption of BA was evaluated using Franz diffusion cells. The accumulated permeation amounts and permeation rate of liposomes, ethosomes, and BA ethosomes modified by SDC were compared. Results: The best formulation consisted of soybean lecithin-SDC-BC (18:1:1) and 35% ethanol. The average EE and the particle size were (93.8 ± 1.6)% and (102.3 ± 3.6) nm, respectively. The accumulated permeation amount of BA ethosomes modified by SDC in 12 h was (99.62 ± 9.44) μg/cm2, which was 1.67, 3.85, and 8.33 times of ethosomes, liposomes, and satuated solution containing 10% isopropanol, respectively. Conclusion: The BA ethosomes, modified by SDC with high EE, obviously enhance the percutaneous absorption of BA and might be one of the most perspective percutaneous preparations.

Mixed nanomicelles loaded with thymopeptides-sodium deoxycholate/phospholipid improve drug absorption / 中国天然药物

AIM@#To improve the absorption of thymopeptides (TH) by preparing sodium deoxycholate/phospholipid-mixed nanomicelles (SDC/PL-MMs).@*METHODS@#TH-SDC/PL-MMs were prepared by a film dispersion method, and then evaluated using photon correlation spectroscopy (PCS), zeta potential measurement, as well as their physical stability after storage for several days. Furthermore, in situ intestinal single-pass perfusion experiments and pharmacodynamics in immunodeficient mice were performed to make a comparison with TH powders and the control drug in absorption properties.@*RESULTS@#A narrow size distribution of nanomicelles, with a mean particle size of (149 ± 8.32) nm and a zeta potential of (-31.05 ± 2.52) mV, was obtained. The in situ intestine perfusion experiments demonstrated a significant advantage in absorption characteristics for TH compared to the other formulations, and oral administration of TH-SDC/PL-MMs potentiated an equivalent effect with i.h. TH in pharmacodynamic studies in immunodeficient mice.@*CONCLUSIONS@#TH-SDC/PL-MMs prepared by a film dispersion method are able to improve the absorption of TH. SDC/PL-MMs might be a good approach for the more effective delivery of drugs like TH.

Preparation and in vivo evaluation of glycgrrhizin acid-sodium deoxycholate/phospholipid-mixed micelles / 中国药学杂志

OBJECTIVE: To improve the oral bioavailability of glycyrrhizin by preparing glyeyrrhizin-sodium deoxycholate/phos-pholipid-mixed micelles (GL-SDC/PL-MMs). METHODS: GL-SDC/PL-MMs was prepared by a film dispersion method. In order toevaluate the property GL-SDC/PL-MMs comprehensively, physical and chemical properties determination, in situ intestinal absorption, and pharmacokinetics test were carried out. RESULTS: The average particle size of drug-loaded micelles prepared by film dispersion method was (82.99±7.5) nm and Zeta potential was (-32.23±1.05) mV. Compared with the control drug, glycyrrhizin loaded in SDC/PL-MMs significantly improved its in situ intestinal absorption. The oral bioavailability was markedly enhanced, indicated by the increase of ρmax to 77.26 μg · mL-1, which was 2.82 times of that of the control drug. CONCLUSION: SDC/PL-MMs is expected to be developed into a new drug delivery systems of GL.

The Effect of Phosphatidylcholine and Deoxycholate Compound Injections to the Localized Adipose Tissue: An Experimental Study with a Murine Model

BACKGROUND: Phosphatidylcholine (PPC) and deoxycholate (DCA) compound has been recently used for the purpose of partial lipolysis and is valued for its efficacy and lower invasiveness compared to liposuction and dermolipectomy used previously. In this article, the authors discuss the efficacy of the PPC dissolved in DCA via an experimental rat study model, along with suggesting a useful animal experimental model for the study of adipose tissue and lipolysis. METHODS: Bilateral inguinal fat pads of an experimental rat were elevated with the deep inferior epigastric vessel as the sole vascular pedicle. Normal saline was injected on one side as a control group and a PPC and DCA compound was injected on the other side. After 4 days, the rats were euthanized for microscopic tissue examination. The pathology was scored by a semiquantitative system in 4 categories: normal fat amount, fat necrosis, inflammatory activity, and stage of fibrosis. A Wilcoxon signed-rank test powered by SPSS packet program was used for statistical analysis and to determine significance. RESULTS: Microscopic examination was performed on the obtained samples, and the experimental data of all four categories showed significant histologic differences compared to the control group. All of the data also showed statistical significance by the Wilcoxon signedrank test (P<0.01). CONCLUSIONS: In the inguinal fat pad rat model, the control group and the experimental group had a differed significantly in the amount of normal fat tissue, inflammation, necrosis, and fibrosis. We recommend the rat inguinal fat pad model used in this study, as it is likely to be useful in related research.

Uso de anfotericina B deoxicolato y sus reacciones adversas en un hospital universitario en Chile / Amphotericin B deoxycholate prescription and adverse events in a Chilean university hospital

Amphotericin B deoxycholate is associated with infusion-related toxicity and renal toxicity. Purpose: To evaluate medical indications of this compound in a tertiary care center, analyze adverse reactions, infusion protocols and outcome of treated patients. Patients and methods: Retrospective analysis of 39 treatments indicated in 33 patients during 2007, exploring indications, infusion protocols and renal protective measures, infusion-related adverse reactions, nephrotoxicity, hypokalemia and outcomes. Results: On average, therapy lasted 12 days (2 to 39) and reached 600 mg of accumulated dose (100 to 1950) respectively. 24-hours infusions were applied in 63.2 percent of prescriptions and 35.9 percent received a 4-6 hour infusion schedule. In addition, 36.8 percent received daily a saline infusion before amphotericin. Adverse reactions were observed in 40 percent of treatments, predominating fever (25 percent). Nonetheless, nephrotoxicity was infrequent (9.4 percent), of low magnitude, only affecting patients without previous renal disease, and not requiring dialysis. Hypokalemia developed in 21.6 percent of treatments. More than half of medical indications were empirical (59 percent), for presumed infections by either filamentous fungi or yeasts. In the subgroup with microbiological information, main indications were invasive aspergillosis (15.4 percent of total), systemic candidiasis (12.8 percent) or meningeal cryptococcosis (10.3 percent). A favorable response was registered in 41 percent, and only 48.5 percent of patients survived. In a multivariate analysis, only age > 60 years remained as an independent factor for developing infusion-related adverse reactions. In the same manner, a SOFA score > 3 and corticosteroids administration at the same time than amphotericin B, were independently associated to a fatal outcome. Conclusion: infusion-related adverse reactions are frequent during amphotericin B deoxycholate therapy, but renal...

Anfotericina B deoxicolato se asocia a reacciones adversas durante la infusión y a nefrotoxicidad. Objetivo: Evaluar las indicaciones de anfotericina B deoxicolato en un hospital universitario, las reacciones adversas asociadas, los protocolos de administración y el desenlace de los pacientes tratados. Pacientes y Métodos: Se efectuó un estudio retrospectivo con el total de tratamientos efectuados durante el año 2007 en el Hospital Clínico de la Universidad de Chile, identificando 39 tratamientos en 33 pacientes. Se analizaron las indicaciones, dosis, protocolos de administración, efectos adversos relacionados a la infusión (fiebre, calofríos, vómitos o flebitis), nefrotoxicidad, hipokalemia y además la evolución de los pacientes. Resultados: La duración promedio del tratamiento fue de 12 días (2-39) con una dosis acumulada promedio de 600 mg totales (100-1.950 mg). Un 63,2 por ciento de los tratados recibió infusiones de 24 horas y 35,9 por ciento, infusiones de 4 a 6 horas. Además, 36,8 por ciento fue sometido a precargas salinas. Un 40 por cientoo de los tratamientos se acompañó de reacciones adversas asociadas a la infusión, predominando la fiebre (25 por ciento). Sin embargo, la nefrotoxicidad fue de baja magnitud (9,4 por cientoo), sólo presente en pacientes sin falla renal previa y en ningún caso determinó el inicio de diálisis. La hipokalemia se presentó en ocho tratamientos (21,6 por ciento). Más de la mitad de las indicaciones fueron empíricas (59 por cientoo), ya fuese para el tratamiento presunto de hongos filamentosos (aspergilosis o mucormicosis) o levaduras (candidiasis sistémica). En el subgrupo con datos micro-biológicos, las principales indicaciones fueron aspergilosis invasora (15,4 por ciento de los 39 tratamientos), candidiasis sistémica (12,8 por ciento) o criptococosis meníngea (10,3 por ciento). Un 41 por cientoo de los pacientes tuvo una respuesta favorable a los tratamientos y sólo 48,5 por cientoo sobrevivió...

Comparative Analysis about the Effect of Isolated Phosphatidylcholine and Sodium Deoxycholate for the Viability of Adipocyte

PURPOSE: Lipobean(R)s, widely used in lipodissolving techniques, contain phosphatidylcholine and sodium deoxycholate as its main substances. They have been approved only as medication for liver disease by the FDA. However, they have been used under various clinical settings without exact knowledge of its action mechanism. The authors designed an in vitro study to analyze the effects of different concentrations of phosphatidylcholine and sodium deoxycholate on adipocytes and other types of cells. METHODS: Human adipose-derived stem cell were cultured and induced to differentiate into adipocytes. Fibroblasts extracted from human inferior turbinate tissue, and MC3T3-E1 osteoblast lines were cultured. Phosphatidylcholine solution dissolved with ethanol was applied to the culture medium at differing concentrations (1, 4, 7, 10 mg/mL). The sodium deoxycholate solution dissolved in DMSO applied to the medium at differing concentrations (0.07, 0.1. 0.4. 0.7 mg/mL). Cells were dispersed at a concentration of 5 x 10(3) cells/well in 24 well plates, and surviving cells were calculated 1 day after the application using a CCK-8 kit. RESULTS: The number of surviving cells of adipocytes, fibroblasts and osteoblasts decreased as the concentration of sodium deoxycholate increased. However, all types of cells that had been processed in a phosphatidylcholine showed a cell survival rate of over 70% at all concentrations. CONCLUSION: This study shows that sodium deoxycholate is the more major factor in destroying adipocytes, and it is also toxic to the other cells. Therefore, we conclude that care must be taken when using Lipobean(R)s as a method of reducing adipose tissue, for its toxicity may destroy other nontarget cells existing in the subcutaneous tissue layer.

Clinical analysis of hematologic diseases complicated by pulmonary fungal infection / 中国实用内科杂志

Objective To analyse the clinical features,predisposing risk factors and treatment of hematologic diseases complicated by pulmonary fungal infection(PFI).Methods The medical records of 97 cases of PFI were retrospectively analyzed.Results Totally 201 fungal strains were obtained from 97 cases of hematologic diseases.The candida strains were 147(73.1%).Two-fungal infection was 17.5%,and secondary bacterial infection was 71.8%;relative death rate was 23.4%.Cure rate of Amphotericin B deoxycholate and Itraconazole was 67.7% and 63.7%.Conclusion Fungal infection is one of the main pathogens in hematologic diseases complicated by infection.Early diagnosis and treatment is the key to beneficial release and long time survival.Amphotericin B deoxycholate and Itraconazole were effective medicines for treated fungal infection.

Intravenous Itraconazole vs. Amphotericin B Deoxycholate for Empirical Antifungal Therapy in Patients with Persistent Neutropenic Fever

BACKGROUND: Amphotericin B dexoycholate is currently the standard empirical antifungal therapy for neutropenic patients with hematologic malignancies and who also have persistent fever that does not respond to antibacterial therapy. The antifungal triazoles offer a potentially safer and effective treatment alternative to Amphotericin B dexoycholate. METHODS: We assessed the efficacy and safety of intravenous itraconazole, as compared with the efficacy and safety of amphotericin B deoxycholate, as an empirical antifungal therapeutic agent in a matched case-control clinical trial from June 2004 to August 2005. RESULTS: Efficacy was evaluated in 96 patients (48 received itraconazole and 48 received amphotericin B deoxycholate) and all the patients who received the study drugs were evaluated for safety. The baseline demographic characteristics were well matched. The overall success rates were 47.9% for itraconazole and 43.8% for amphotericin B deoxycholate (% difference: 4.1 % [95% confidence interval for the difference: -15.8 to 24]), which fulfilled the statistical criteria for the non-inferiority of itraconazole. The proportions of patients who survived for at least seven days after discontinuation of therapy or who were prematurely discontinued from the study were not significantly different between the two groups. The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in both groups. More patients who received amphotericin B deoxycholate developed nephrotoxicity, hypokalemia or infusion-related events than did those patients who received itraconazole (nephrotoxicity: 16.7% vs. 1.8%, hypokalemia: 66.7% vs. 24.6%, and infusion-related events: 41.7% vs. 3.5%, respectively). CONCLUSIONS: Intravenous itraconazole is as effective as amphotericin B deoxycholate and it is generally better tolerated than amphotericin B deoxycholate when it is given as empirical antifungal therapy for Korean patients with persistent neutropenic fever.

Comparison of Effects and Side Effects of Amphotericin B Deoxycholate Infusion over 6 versus 24 Hours in Children with Cancer / 대한소아혈액종양학회지

PURPOSE: This study was performed to compare the effects and side effects of amphotericin B deoxycholate infusion over 6 versus 24 hours in febrile children with cancer. METHODS: Twenty-four children with cancer who were mostly neutropenic, febrile and suspected to have fungal infection and treated with amphotericin B deoxycholate from March 2001 to July 2002 at the Yeungnam University Hospital, Department of Pediatrics were enrolled for a cross-over study. All patients received 0.5 mg/kg amphotericin B deoxycholate infusion for average 7 days by two different infusion rates, one group by continuous infusion over 24 hours and the other by rapid infusion over 6 hours with at least 4 weeks of washout period. The side effects related to the infusion rates, fever, chilling or rigor, vomiting, headache, serum and urine electrolytes, beta2-microglobulin and creatinine clearance were monitored. The effect of amphotericin B deoxycholate infusion were studied by the days required for defervescence. RESULTS: There were no significant differences (P=0.11) in the effects between continuous and rapid infusion. But less side effects of chilling or rigor (P=0.01) were observed when amphotericin B deoxycholate was infused continuously. The serum phosphate (P=0.05) and magnesium (P=0.04) were lower and creatinine clearance was more reduced (P=0.01) when it was infused rapidly. CONCLUSION: Continuous infusion over 24 hours of amphotericin B deoxycholate could reduce the nephrotoxicity, such as hypophosphatemia, hypomagnesemia, low creatinine clearance and chilling reactions related to the rapid infusion without compromising the effects of amphotericin B deoxycholate in children with cancer.

Cytosolic Glutathione S-Transferase Change after Deoxycholate Exposure in Colon Cancer Cell Lines

PURPOSE: Bile acids (especially deoxycholate) was known to be toxic and mutagenic on colon epithelium. They proposed at least four mechanisms for the bile acid toxicity. It is the one of these mechanisms that bile acid inhibits the xenobiotic metabolizing enzyme activity (esp glutathione S-transferase, GST). So we measured the cytosolic GST level of colon carcinoma cell lines after deoxycholate exposure whether or not the deoxycholate lowered the cytosolic GST activity. METHODS: Three colon cancer cell lines (LoVo, SW480, HT29) were used for this study. We calculated the cellular toxicity by MTS method. And cytosolic GST activity was measured according to the method as Habig described. For total GST activity, 2.5 mM 1-chloro-2,4-dinitrobenzene was used for substrate, and measured as absorbance in 340 nm. RESULTS: Basal cytosolic GST level for LoVo, SW480, HT29 cell line was 514.59+/-27.01, 291.63+/-38.44 and 344.58+/-47.92 nmol/min/mg cytosol protein. GST level did not changed significantly after 5 days culture without DCA. But GST level was decreased significantly to 128.63+/-21.35, 134.33+/-41.76 and 163.10+/-22.73 nmol/min/mg cytosol protein each cell line after 5 days deoxycholate exposure (p<0.005). CONCLUSION: Cytosolic GST level was lowered significantly after deoxycholate exposure for 5 days. One of the mechanisms of bile acid toxicity for colon cancer cell is proposed to inhibit cytosolic GST activity.

Comparison of 2 decellularizing methods to prepare rat acelluar allograft spinal cord scaffold / 第三军医大学学报

Objective To compare the effect of 2 decellularizing methods,sodium deoxycholate plus Triton X-100 or plus DNase and Rnase,in the preparation of acelluar allograft spinal cord scaffold in order to provide an ideal natural spinal cord scaffold to bridge the nerve gap.Methods Spinal cord was removed from health rats,and then decellularized by the method of freeze thawing(immersing in 3% sodium deoxycholate followed by the mixture of 1?103 U/ml DNase and RNase),or by chemical extraction(immersing in 1% Triton X-100 and then 1% sodium deoxycholate).HE staining,myelin staining and scanning electron microscopy(SEM) were employed to evaluate the spinal cord scaffold after the 2 methods of decellularization.Results Both cells and myelin were completely decellularized with the 2 methods.In cross section,network of the extracellular matrix was presented without axon,sheath and cells nucleus being seen in the scaffold.Typical network of empty tubes were viewed in longitudinal sections.Conclusion An ideal spinal cord scaffold can be produced with these 2 decellularizing methods in tissue engineering.The scaffold made by the 2 methods have similar three dimensional structure with normal spinal cord,so can be used as a graft to bridge the nerve gap directly or as a scaffold to implant the seeding cells in spinal cord tissue engineering.