Clinical effects of Jiakang Pingxiao prescription combined with methiimidazole on hyperthyroidism / 中国基层医药

Objective:To investigate the clinical effects of Jiakang Pingxiao prescription combined with methiimidazole on hyperthyroidism. Methods:A total of 100 patients with hyperthyroidism admitted to Shanxian Central Hospital from February 2018 to January 2021 were included in this study. They were randomly divided into a study group and a control group, with 50 patients in each group. The control group was treated with methiimidazole, and the study group was treated with Jiakang Pingxiao prescription combined with methiimidazole. Thyroid function, serum levels of osteocalcin (OCN), β-CTx, hypersensitive C-reactive protein, and interleukin-6 (IL-6) were compared between the two groups. Results:After treatment, serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) in the study group were (3.10 ± 1.36) mU/L, (5.76 ± 1.25) pmol/L, (15.22 ± 1.95) pmol/L, respectively, which were significantly lower than (4.88 ± 1.47) mU/L, (7.13 ± 1.32) pmol/L, (19.07 ± 2.02) pmol/L in the control group ( t = 5.27, 4.71, 6.29, all P < 0.05). Serum OCN, β-CTx, hS-CRP, and IL-6 in the study group were (17.36 ± 2.62) μg/L, (0.32 ± 0.04) μg/L, (4.07 ± 0.86) mg/L, and (1.38 ± 0.21) pg/L, respectively, which were significantly lower than (26.05 ± 2.88) μg/L, (0.51 ± 0.09) μg/L, (6.23 ± 0.91) mg/L, (1.89 ± 0.28) pg/L in the control group ( t = 12.37, 10.40, 7.39, 8.57, all P < 0.05). The incidence of adverse reactions in the study group was significantly lower than that in the control group [6.00% (3/50) vs. 12.00% (3/50), χ2 = 14.78, P < 0.05). Conclusion:Jikang Pingxiao prescription combined with methiimidazole can effectively reduce the inflammatory responses in patients with hyperthyroidism, inhibit the expression of OCN and β-CTX in the serum, and improve thyroid function. The combined method is scientific and reasonable, and is suitable for clinical application. It has good therapeutic effects on hyperthyroidism and is worthy of clinical promotion.

Preliminary study on high throughput screening small molecules targeting Gram-negative bacilli outer membrane protein BamA / 中华检验医学杂志

Objective:High-throughput screening to obtain small molecular compounds against Gram-negative bacilli by targeting BamA outer membrane protein.Methods:The sybyl-X2.1 software was used to perform high-throughput virtual screening of small molecular compounds in Chemdiv compound library based on the molecular docking. The top 150 hits by high-throughput screening were re-screened through in vitro biological experiments. The top 4 small molecules with obvious antibacterial activity were selected for in-depth molecular docking analysis, and the small molecule 8308-0401 with the highest docking score was selected for further experiments. The antibacterial effect of 8308-0401 combined with rifampicin was tested by checkerboard assay. Finally, the affinity between 8308-0401 and BamA was tested by plasma surface resonance assay. Results:The docking score of the top 150 hits calculated by high-throughput virtual screening had a mean value of 5.63. In vitro biological experiments showed that small molecules 8308-0401, 8365-1335, C066-2507 and L582-0346 exhibited strong antibacterial activity. Among those molecules, 8308-0401 showed the highest molecular docking score, and synergistic antibacterial activity against both types of strains and clinical isolates when combined with rifampicin. 8308-0401 has a strong affinity to BamA with binding a constant of 182 μmol/L. Conclusion:The small molecule 8308-0401 exerts antibacterial activity against Gram negative bacilli by targeting the outer membrane protein BamA.

Synergistic antimicrobial potential of EGCG and fosfomycin against biofilms associated with endodontic infections

Abstract Objective This study aimed to evaluate the cytotoxicity and synergistic effect of epigallocatechin gallate (EGCG) and fosfomycin (FOSFO) on biofilms of oral bacteria associated with endodontic infections. Methodology This study determined minimum inhibitory and bactericidal concentration (MIC/MBC) and fractionated inhibitory concentration (FIC) of EGCG and FOSFO against Enterococcus faecalis, Actinomyces israelii, Streptococcus mutans, and Fusobacterium nucleatum. Monospecies and multispecies biofilms with those bacteria formed in polystyrene microplates and in radicular dentin blocks of bovine teeth were treated with the compounds and control chlorhexidine (CHX) and evaluated by bacterial counts and microscopy analysis. Toxicity effect of the compounds was determined on fibroblasts culture by methyl tetrazolium assays. Results The combination of EGCG + FOSFO demonstrated synergism against all bacterial species, with an FIC index ranging from 0.35 to 0.5. At the MIC/FIC concentrations, EGCG, FOSFO, and EGCG+FOSFO were not toxic to fibroblasts. EGCG+FOSFO significantly reduced monospecies biofilms of E. faecalis and A. israelli, whereas S. mutans and F. nucleatum biofilms were eliminated by all compounds. Scanning electron microscopy of multispecies biofilms treated with EGCG, EGCG+FOSFO, and CHX at 100x MIC showed evident biofilm disorganization and substantial reduction of extracellular matrix. Confocal microscopy observed a significant reduction of multispecies biofilms formed in dentin tubules with 84.85%, 78.49%, and 50.6% of dead cells for EGCG+FOSFO, EGCG, and CHX at 100x MIC, respectively. Conclusion EGCG and fosfomycin showed a synergistic effect against biofilms of oral pathogens related to root canal infections without causing cytotoxicity.

Evaluation of antihyperlipidemic activity of gugulipid alone and in combination with different dosage of atorvastatin in triton-induced hyperlipidemic rodent model: Exploring a possible synergistic activity

Background: Gugulipid obtained from Commiphora mukul carries a long history of safe and efficacious use in hyperlipidemia as per Ayurvedic literature. Statins like atorvastatin are a highly prescribed hypolipidemic drug but not free from potentially serious adverse effects. Aims and Objectives: The present study was designed to establish antihyperlipidemic activity of gugulipid in triton-induced hyperlipidemic rats in comparison to atorvastatin and simultaneously to explore the combination of gugulipid and atorvastatin for any synergistic activity. Materials and Methods: Male Wistar albino rats (20) were divided equally into vehicle (2% gum acacia) (Group I), gugulipid only 6.75 mg/kgbw (Group II), atorvastatin 7.2 mg/kgbw only (Group III), and gugulipid 6.75 mg/kgbw and atorvastatin in 7.2 mg/kgbw combination (Group IV) in Phase 1 study. In Phase 2, additional three groups were created with five rats in each receiving gugulipid 6.75 mg/kgbw with atorvastatin at 5.4 mg/kgbw, 3.6 mg/kgbw, and 1.8 mg/kgbw dosage, respectively (Groups V–VII). Hyperlipidemia was induced by single intraperitoneal injection (400 mg/kgbw) of triton after 7 days of feeding with respective agents dissolved in vehicle through oral route. Results: Regarding total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL), Gr II was found superior to Gr I but inferior to others (P < 0.01). Gr IV prevented the rise of TC and TG significantly in comparison to Gr V, VI, and VII (P < 0.01) whereas Groups V and VI having non-significant difference in between, both differed significantly (P < 0.01) with Gr VII. Groups IV, V, and VI prevented the rise of serum LDL significantly (P < 0.01) from Group VII. Conclusion: Gugulipid showed significant antihyperlipidemic activity and was found to be optimally efficacious and safe in combination with even reduced dose of atorvastatin.

Current status of antimicrobial therapy for tuberculosis / 中国基层医药

Multidrug-resistant tuberculosis has a long treatment course and a low sputum-negative conversion rate, which have always been the treatment challenges. New drugs for multidrug-resistant tuberculosis have been constantly explored by scholars worldwide. Multiple antibacterial drugs have been found to have the therapeutic effects on multidrug-resistant tuberculosis. Treatment options that can shorten the duration of tuberculosis are also being explored. Addition of certain antibacterial drugs has been found to shorten the duration of tuberculosis. This paper reviews the effects of antibacterial drugs against tuberculosis.

Orofacial antinociceptive effects of perillyl alcohol associated with codeine and its possible modes of action

Abstract This study evaluated the orofacial antinociceptive effect of (S)-(-)-perillyl alcohol (PA) associated with codeine (C) and investigated the possible molecular anchorage mechanisms of PA. Mice (n = 5 per group) were treated with PA alone and associated with codeine and assigned to the following groups: 75.0 mg/kg PA; 75.0 mg/kg PA + C 30 mg/kg; PA 37.5 mg/kg + C 15.0 mg/kg; C 30.0 mg/kg; and control. Nociception was induced by formalin, capsaicin, and glutamate, and was quantified based on the duration (in seconds) of face grooming. The possible mechanisms of action were evaluated by molecular docking study. In the formalin test, PA75/C30 presented an effect in the neurogenic (p < 0.0001) and inflammatory (p < 0.005) phases. Mice treated with PA75 (p < 0.0001) and PA75/C30 (p < 0.0005) showed a reduced nociceptive behavior in the capsaicin test. Glutamate-induced nociception also was blocked by PA75 (p < 0.0005) and C30 (p < 0.0005). The molecular anchorage analysis indicated high negative binding energy values for the evaluated receptors, especially glutamate receptors (AMPA -79.57 Kcal/mol, mGLUR6 -71.25, and NMDA -66.33 Kcal/mol). PA associated with codeine showed orofacial antinociceptive activity, with theoretical evidence of interaction with glutamate receptors.

Atividades farmacológicas da manteiga de bacuri (Platonia insignis Mart): revisão integrativa / Pharmacological actions of bacuri butter (Platonia insignis Mart): an integrative review

RESUMO Objetivo identificar as atividades farmacológicas da manteiga de bacuri (Platonia insignis Mart.). Métodos revisão integrativa, realizada nas bases de dados Literatura Latino-americana e do Caribe em Ciências da Saúde, Cumulative Index to Nursing and Allied Health Literature, EMBASE, MEDLINE/PubMed, Web of Science, Cochrane Library e SCOPUS, sem delimitação temporal e de idioma. A seleção se constituiu de 13 ensaios pré-clínicos. A avaliação das informações ocorreu de forma descritiva, confrontando com os achados pertinentes. Resultados observou-se que 50,0% das publicações foram indexadas na MEDLINE/PubMed, maioria das publicações ocorreram na Inglaterra (61,5%), seguidas do Brasil e dos Estados Unidos, ambos com 13,3%. Destaca-se que 100,0% dos artigos foram ensaios pré-clínicos; atividades farmacológicas para antioxidante (38,4%) e antileishmanicidas (30,7%). Registrou-se que 38,4% dos ensaios apresentaram testes de toxicidade. Conclusão a manteiga de bacuri (Platonia insignis Mart.) apresentou atividades farmacológicas em ensaios pré-clínicos, como antioxidantes, antileshimaniose, anticonvulsivante e cicatrização de feridas.

ABSTRACT Objective to identify the pharmacological activities of bacuri butter (Platonia insignis Mart.). Methods an integrative review, carried out in the databases of Latin American and Caribbean Literature in Health Sciences, Cumulative Index to Nursing and Allied Health Literature, EMBASE, MEDLINE/PubMed, Web of Science, Cochrane Library and SCOPUS, without the time and language restriction. The selection consisted of 13 pre-clinical trials. The information assessment descriptively took place, comparing with the pertinent findings. Results it was observed that 50.0% of the publications were indexed in MEDLINE/PubMed, most publications were from England (61.5%), followed by Brazil and the United States, both with 13.3%. It is noteworthy that 100.0% of the articles were pre-clinical trials; pharmacological activities for antioxidants (38.4%) and antileishmanicides (30.7%). It was found that 38.4% of the trials presented toxicity tests. Conclusion bacuri butter (Platonia insignis Mart.) Showed pharmacological activities in pre-clinical trials, such as antioxidants, antileshimaniasis, anticonvulsant and wound healing.

In vitro effectivity of three approved drugs and their synergistic interaction against Leishmania infantum / Efectividad in vitro de tres fármacos aprobados y su interacción sinérgica contra Leishmania infantum

Introduction: Leishmaniasis remains one of the neglected tropical diseases. Repurposing existing drugs has proven to be successful for treating neglected tropical diseases while combination therapy is a strategic alternative for the treatment of infectious diseases. Auranofin, lopinavir/ritonavir, and sorafenib are FDA approved drugs used in the treatment of diverse diseases by acting on different essential biological enzymes. Objective: To evaluate the effects of monotherapy and combined therapies with the three drugs against Leishmania infantum. Materials and methods: We compared the leishmanicidal effects of the three drugs on promastigotes in vitro as regards the parasite count, the drug concentration providing a half-maximal response, and the ultrastructural changes of the parasite. We determined the fractional inhibitory concentration index of combined drugs in two ways, as well as the activity of the three drugs together to establish their synergetic effect. Results: The monotherapy with the three drugs was effective with auranofin showing the best leishmanicidal effect (EC50=1.5 µM), whereas sorafinib reduced parasite growth at EC50=2.5 µM. The scanning electron microscopy of promastigotes from all treated media showed distortion in the shape with loss of flagella and bleb formation. Acidocalcinosis was evident by transmission electron microscopy with all treatments suggesting apoptosis. Treatment with lopinavir/ritonavir showed signs of autophagy. The two-way combination of the drugs led to additive interactions while the combination of the three drugs showed synergistic action. Conclusion: Each drug when used as monotherapy against Leishmania spp. was effective, but the combination therapy was more effective than the individual drugs due to the additive or synergistic effects.

Introducción. La leishmaniasis sigue siendo una de las enfermedades tropicales desatendidas. La reutilización de medicamentos existentes ha demostrado ser exitosa para tratar enfermedades tropicales desatendidas y la terapia combinada es una alternativa estratégica para el tratamiento de enfermedades infecciosas. Auranofin, lopinavir/ritonavir y sorafenib son medicamentos aprobados por la Food and Drug Administration (FDA) de Estados Unidos utilizados en el tratamiento de diversas enfermedades, pues actúan sobre diferentes enzimas biológicas esenciales. Objetivo. Evaluar los efectos terapéuticos de la monoterapia y de los tres fármacos combinados contra Leishmania infantum. Materiales y métodos. Los efectos leishmanicidas de los tres fármacos sobre los promastigotes se compararon in vitro en cuanto al recuento de parásitos, la concentración del fármaco que proporcionara una respuesta semimáxima y los cambios ultraestructurales del parásito. Se calculó el índice de concentración inhibitoria de fracciones de fármacos combinados de dos maneras y la actividad de los tres fármacos juntos para determinar el efecto sinérgico. Resultados. La monoterapia con los tres medicamentos fue efectiva, pero la auranofina tuvo el mejor efecto antileishmanicida con un CE50 de 1,5 µM, en tanto que el sorafinib redujo el crecimiento del parásito con un CE50 de 2,5 µM. La microscopía electronica de barrido de promastigotes de todos los medios tratados mostró una distorsión en la forma, con pérdida de flagelos y formación de ampollas. La acidocalcinosis fue evidente por microscopía electrónica de transmisión con todos los tratamientos, lo que sugiere apoptosis. El tratamiento con lopinavir/ritonavir mostró signos de autofagia. La combinación de dos medicamentos condujo a interacciones aditivas, mientras que la combinación de las tres drogas produjo una acción sinérgica. Conclusión. Los tres medicamentos usados como monoterapia contra Leishmania spp. fueron efectivos, pero el tratamiento combinado lo fue en mayor medida debido a los efectos aditivos o sinérgicos.

Diabetes as a risk factor of acute kidney injury in vancomycin users: an observational and prospective study

Diabetes was investigated as a risk factor for nephrotoxicity induced by vancomycin. In the present study, the drug's nephrotoxic effect was indirectly evaluated by Glomerular Filtration Rate, albuminuria and serum levels of creatinine and urea on the 1st, 7th and 14th days of vancomicyn therapy in a group of diabetic and non-diabetic patients, with and without previous nephropathy. The correlations between investigated variables (including the population's epidemiological profile and hospital care) were measured by the Spearman test. The sample consisted of 132 patients, predominantly male diabetic patients with previous nephropathy, over 40 years, receiving ≥ 10 grams of vancomycin for the treatment of infectious diseases and showing satisfactory clinical outcomes. A risk of vancomycin drug interaction with potential nephrotoxic outcome was observed in 36.4% of patients who used multiple drugs. Furthermore, 80% of patients had an increase of at least 0.5 mg.dL-1 in baseline serum levels of creatinine and urea at the end of the study. This was more common among the diabetic patients with previous nephropathy, showing higher albuminuria and a reduction in the Glomerular Filtration Rate. Therefore, it has been recommended that the use of vancomycin in diabetic patients should be in careful dosages and that kidney functioning be monitored.

Synergistic effect of sertraline and disulfiram against multidrug resistant bacteria as a new alternative to drug repositioning

The repositioning of approved drugs is atopic of interest for the academy and the pharmaceutical industry. The synergistic combination of these drugs can be successful in the treatment of infections caused by resistant bacteria. This study aimed to assess the in vitro synergistic antibacterial activity of sertraline and disulfiram and their interaction with ciprofloxacin and sulfamethoxazole/trimethoprim. We determined the minimum inhibitory concentration, the minimum bactericidal concentration and the fractional inhibitory concentration index. Eighteen bacterial strains were used, being nine American Type Culture Collection reference strains and nine multidrug resistant clinical isolates. Synergy was detected between sertraline and disulfiram against a strain of Staphylococcus aureusATCC 25923 and a clinical isolate of S. aureus. When associated to sulfamethoxazole/trimethoprim and ciprofloxacin, sertraline and disulfiram showed eight synergistic events, which occurred against three different standard strains and two multidrug resistant clinical isolates. When the minimum bactericidal concentration was determined, the bactericidal activity of sertraline was enhanced with disulfiram. Our results suggest that these drugs, widely used to treat depression and chronic alcoholism, have antibacterial potential individually, in association, and combined with antimicrobials, what makes their repositioning a promising therapeutic alternative for the effective treatment of infections caused by multidrug resistant bacteria.

Tannic acid enhances cisplatin effect against hepatocellular carcinoma HepG2 by endoplasmic reticulum stress pathway / 重庆医学

Objective To investigate the synergistic effects of tannic acid(TA) and cis-dichlorodiamine platinum(CDDP) on hepatocellular carcinoma HepG2 cells and its activation situation of endoplasmic reticulum stress(ERS) pathway.Methods Human hepatocellular carcinoma HepG2 cells were divided into the control group,TA group,CDDP group and TA+CDDP group,and were cultured in vitro for 24 h.The growth inhibitory effect of medication on HepG2 cells was detected by MTT assay.The pharmacodynamics synergistic effect between the two drugs was analyzed by the drug interaction index,drug dose reduction index and equivalent graphical method.The nucleus changes were observed by DAPI staining.Real time fluorescent quantitative PCR(q-RT-PCR) and Western blot were used to detect the levels of ERS markers glucose regulated protein (GRP)78 and GRP94.Results TA and CDDP had dose-dependent growth inhibition effect on HepG2 cells,their median effective concentrations(IC50) were 360.00 μmol/L and 1.80 μg/mL respectively.The combination treatment of 180.00 μmol/L TA and 0.90 μg/mL CDDP on HepG2 cells could enhance the inhibitory effect on cell growth.Ta and CDDP had synergistic effect for inhibiting hepatocellular carcinoma cells growth.Compared with the TA group and CDDP group,cell shrinkage and rounding were accelerated in the combined group,apoptotic cells were increased,nuclear had pyknosis,irregular edge and dense staining,nuclear fragmentations were increased and the expressions of GRP78 and GRP94 were up-regulated.Conclusion TA can enhance the effect of CDDP on anti-hepatic carcinoma HepG2 cells,and the synergy mechanism may be related to the activation of ERS pathway.

In vitro antifungal activity of four antifungal agents alone or in combination against Exophiala dermatitidis biofilms / 中华皮肤科杂志

Objective To evaluate the in vitro antifungal activity of 4 antifungal agents alone or in combination against Exophiala dermatitidis (E.dermatitidis) biofilms.Methods E.dermatitidis biofilms were prepared by using a modified 96-well plate-based method.The in vitro antifungal activity of amphotericin B,voriconazole,itraconazole and caspofungin alone or in combination against E.dermatitidis biofilms were investigated via the broth microdilution checkerboard technique.Results The sessile minimum inhibitory concentration ranges resulting in 50％ (SMICS0) and 80％ inhibition (SMIC80) of E.dermatitidis biofilms were all ＞ 32 mg/L for itraconazole,voriconazole and caspofungin,and the SMIC50 and SMIC80 ranges of amphotericin B were 1-2 mg/L and 4-8 mg/L respectively.The combination of amphotericin B with voriconazole showed synergistic inhibitory effects against E.dermatitidis biofilms,while the combination of amphotericin B with itraconazole or caspofungin,as well as the combination of voriconazole with caspofungin,revealed no synergistic effects.No antagonistic effect was observed in any of the combinations.Conclusion Amphotericin B appears more active against E.dermatitidis biofilms,and the combination with voriconazole can enhance the anti-biofilm effects against E.dermatitidis biofilms.

Antifungal Activity of Eugenol and its Association with Nystatin on Candida albicans

Objective: To evaluate the anti-Candida effect of eugenol and its antimicrobial interaction with nystatin. Material and Methods: The antimicrobial potential was assessed by microdilution technique (M27A3 reference method), by determining the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) against C. albicans (ATCC 90028). The possible action of eugenol on the fungal cell wall was evaluated with the assistance of the osmotic protector sorbitol (0.8 M). The antimicrobial interaction with nystatin was assessed through the checkerboard method. All tests were performed in triplicate. Results: All groups showed reductions in PI and GBI values and improvements in oral health knowledge, but IG1 and IG2 showed statistically significant differences in these variables compared to CG. Conclusion: The eugenol has antifungal activity against C. albicans and its mechanism of action is probably not related to damage to the fungal cell wall. Association between eugenol and nystatin was not found to be an advantageous possibility for growth inhibition of C. albican.

Combination chemotherapy of L-proline-m-bis (2-chloroethyl) amino-L-phenylalanyl-L-norvaline ethyl ester hydrochloride with anti-cancer drugs in human hepatocellular carcinoma / 药学学报

L-Proline-m-bis (2-chloroethyl) amino-L-phenylalanyl-L-norvaline ethyl ester hydrochloride (MF13) is a new anticancer tripeptide. Our previous study in vitro and in vivo showed that MF13 had anti-proliferative activities in a panel of human hepatocellular carcinoma (HCC) cell lines from different origin. In the present study, we focused on the inhibition effect on HCC of MF13 combined with other anti-cancer drugs. The results of combination chemotherapy in vitro indicated that the combination of MF13 with mitomycin C (MMC) at appropriate concentrations led to a synergistic effect; however, the combination of MF13 with vincristine (VCR) showed no synergistic effect. In the Bel-7402 tumor bearing nude mice, the antitumor effect of the groups of 2 mg·kg-1 MF13 + 2 mg·kg-1 MMC or 2 mg·kg-1 MF13 + 50 mg·kg-1 cyclophosphamide (CTX) exhibited synergistic anticancer efficacies while the group of 2 mg·kg-1 MF13 + 0.3 mg·kg-1 VCR did not have the same effect. Based on our data, we believe that MF13 can be considered as a potential agent against human hepatocellular carcinoma no matter how treated, alone or combined with other drugs.

In vitro synergistic effect of tetrandrine on ketoconazole against Candida parapsilosis complex / 中华皮肤科杂志

Objective To evaluate the in vitro synergistic effect of tetrandrine on ketoconazole against Candida parapsilosis complex.Methods According to the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines,the microdilution checkerboard method was used to evaluate in vitro antifungal activities of ketoconazole alone and in combination with tetrandrine against 21 clinical isolates of Candida parapsilosis complex based on the fractional inhibitory concentration index (FICI).Antifungal effects of the above drugs at different time points were evaluated by the XTT assay,and then time-killing curves were drawn and assessed to investigate the in vitro dynamic antifungal activity.Results The minimum inhibitory concentrations (MICs) of tetrandrine and ketoconazole alone against 21 clinical isolates of Candida parapsilosis complex were 32-64 mg/L and 0.031 25-2 mg/L,respectively.When ketoconazole was combined with tetrandrine,MICs of tetrandrine and ketoconazole were reduced to 2-8 mg/L and 0.008-0.25 mg/L respectively,and the FICI ranged from 0.09 to 0.5.The time-killing curves revealed that the fungal growth was delayed obviously in the combination group compared with the ketoconazole alone group and tetrandrine alone group.Conclusion Tetrandrine has obvious synergistic effects on ketoconazole against Candida parapsilosis complex in vitro.

The Complement Inhibition of Ursolic Acid and Tetrandrine on Tumor Related Signaling Pathways and Their Synergistic Antitumor Proliferation Effects / 浙江中医药大学学报

[Objective]This study was aimed to research the synergistic antitumor proliferation effects and their best proportion of ursolic acid(UA) and tetrandrine(Tet), a pair of compounds isolated from Chinese herbs which showed complement inhibition on the multiple signal pathways. [Methods] The reporter assays on tumor-related signal pathways for MAPK/ERK, MAPK/JNK, NF-κB, Wnt, Notch, Cell Cycle, Myc/Max and Hypoxia were used to study the effect of five different Chinese herbal compounds on tumor proliferation,it was concluded cepharanthine(Cep), Tet, 18α-glycyrrhetinic acid(18α-Gly), UA and luteolin(Lut). MTT assay and crystal violet staining were used to study the antiproliferative effect of 15 different compounds for the tumor cells of MDA-MB-231,SW480,MG63,PC3,DU145,HCT116,143B and MDA-MB-468, which is consisted with Cep, Tet, 18α-Gly, UA and Lut for the 15 different compounds. Coefficient of drug interaction(CDI) method was used to detect the synergistic effect of the two compounds. Combination of index(CI) and isobologram method was used to screen the best ratio of compounds in their antiproliferative effects. [Results] The signal pathway reporter assay showed that UA and Tet could complementarily inhibit tumor-related signaling pathways. And the results also showed that UA and Tet could induce synergetic anti-tumor cell proliferation in vitro. Furthermore, the optimal ratio of UA and Tet was 9:1 by using isobologram and CI method. [Conclusion] UA and Tet can be inhibited and complemented by 8 tumor-related signaling pathways, and we used MTT assay and crystal violet staining or other methods to confirm the synergistic antitumor proliferation effects, furthermore, the optimal proportion for UA and Tet were screened, and it provided a new insight to develop new anticancer formula in research.

In vitro antifungal activity of tacrolimus alone or in combination with itraconazole or terbinafine against Exophiala dermatitidis / 中华皮肤科杂志

Objective To evaluate in vitro antifungal activity of tacrolimus combined with itraconazole or terbinafine against Exophiala dermatitidis (E.dermatitidis).Methods The minimum inhibitory concentrations (MICs) of itraconazole and terbinafine against 12 strains of E.dermatitidis were determined using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution susceptibility method (M38-A2 Document).A broth microdilution checkerboard method was used to evaluate the in vitro antifungal activity of tacrolimus combined with itraconazole or terbinafine against E.dermatitidis.Results The MIC ranges of terbinafine and itraconazole against E.dermatitidis were 0.060-0.125 mg/L and 0.5-1 mg/L,respectively.The combination of tacrolimus with terbinafine showed synergistic inhibitory effects against 5 strains of E.dermatitidis,while the combination of tacrolimus with itraconazole revealed synergistic effects against 10 strains of E.dermatitidis.No antagonism was observed in either of the two combinations.Conclusion In vitro combination of tacrolimus with itraconazole or terbinafine can enhance the antifungal activity of itraconazole or terbinafine against E.dermatitidis.

Hemodynamic Effects of Co-administration of Midazolam during Anesthesia Induction with Propofol and Remifentanil in Hypertensive Patients / 고신대학교의과대학학술지

OBJECTIVES: Propofol, midazolam and remifentanil are commonly used for clinical anesthesia. We compared the effects of midazolam-propofol-remifentanil and propofol-remifentanil on hemodynamic responses during anesthesia induction in hypertensive patients. METHODS: Seventy-six hypertensive patients with ASA II-III were assigned to receive midazolam-propofol (group MP; n = 38) or propofol (group P; n = 38). Anesthesia was induced with midazolam 0.03 mg/kg (group MP) or saline 0.03 ml/kg (group P). After two minutes, propofol 1.0 mg/kg (group MP) or 1.5 mg/kg (group P) i.v. bolus was administered. Simultaneously, 4 ng/ml of remifentanil target controlled infusion (TCI) was administered in both groups. Anesthesia was maintained using sevoflurane and 2 ng/ml of remifentanil TCI. Systolic, diastolic, and mean blood pressure (SBP, DBP, and MBP) and heart rate (HR) were measured before induction, 2 min after midazolam or normal saline, 2 min after propofol, 1 min after rocuronium, and immediately, 1 min, 2 min, and 3 min after intubation. RESULTS: SBP, DBP, and MBP decreased after propofol administration and increased immediately after intubation in both groups (P < 0.05). After intubation, SBP, DBP, and MBP decreased more than baseline values in either group. Although the overall BP of Group P was lower than that of Group MP, there were no significant differences except for SBP at 2min after intubation (P < 0.05). HR was no significant difference in either group. CONCLUSION: Our results suggest that midazolam-propofol-remifentanil has similar hemodynamic effect with propofol-remifentanil during anesthesia induction in hypertensive patients.

Síndrome de piernas inquietas (enfermedad de Willis-Ekbom): seguimiento a largo plazo de una serie de pacientes / Restless legs syndrome: long-term follow-up of a series of patients

Background: Restless legs syndrome (RLS) affects 10% of the general population. Aim: To analyze a series of patients with a minimum follow-up period of four years, treated during an interval of 14 years. Material and Methods: Retrospective analysis of medical records of 200 patients assessed and followed by the authors at a private outpatient clinic. Results: Fifty patients aged 25 to 90 years (34 females), who had a mean follow-up of 6,3 years (range 4-14 years), were selected. Sixty percent responded to therapy that initially consisted in dopamine agonists in 78% of cases. Thirty four percent remained symptomatic and 4% worsened. RLS severity scale improved from an initial score of 19,2 to 12,5 at the last follow-up visit (p < 0.05). Thirty-three patients (66%) experienced an overall worsening of symptoms beyond pretreatment levels during follow-up. The strategies to overcome this augmentation were the change to another agonist, use of ligands such as pregabalin and gabapentin, opioids and iron. Low ferritin was common in most of the patients in whom it was measured (24 of 45 results), mainly in those with augmentation (p < 0,05). Six percent of patients treated with dopamine agonist developed an impulse control disorder. Conclusions: RLS is a treatable condition during a long period of follow-up in most patients. We found a high rate of potentiation at presentation which can be explained by the inadequate use of high doses of dopaminergic agents.

Effect of Bruton’s tyrosine kinase inhibitors combined with bortezomib on human multiple myeloma cell lines and its mechanism / 第二军医大学学报

Objective To explore the effect of Bruton’s tyrosine kinase (BTK) inhibitors, ibrutinib and AVL-292 alone or in combination with proteasome inhibitor bortezomib on human multiple myeloma (MM) cell lines H929 and RPMI8226 and the related mechanism. Methods H929 and RPMI8226 cells were treated with ibrutinib or AVL-292 alone or in combination with bortezomib in vitro. The cell viability was detected by CCK-8 assay after treatment, the apoptosis levels were analyzed by flow cytometry, the expression and phosphorylation levels of BTK pathway proteins and apoptosis-related proteins were measured by Western blotting analysis. Results The proliferation of H929 and RPMI8226 cells was inhibited by ibrutinib and AVL-292 in a dose-dependent manner. The 48 h median inhibitory concentration (IC50) values of ibrutinib in the two cell lines were (10. 41±3. 29) μmol/L and (51. 65±13. 58) μmol/L, respectively, and the 48 h IC50 values of AVL-292 were (7. 77±2. 99) μmol/L and (6. 44±1. 06) μmol/L, respectively. The inhibition effects of different concentrations of ibrutinib (5 μmol/L, 10 μmol/L) and AVL-292 (5 μmol/L, 10 μmol/L) combined with different concentrations of bortezomib (5 nmol/L, 10 nmol/L, 20 nmol/L, and 50 nmol/L) were significantly higher than those of the corresponding single agents (P<0. 05, P<0. 01); the coefficients of concordance (R) of different combinations were all above 1. 0. After treatment with 10 μmol/L ibrutinib, 10 μmol/L AVL-292 and 20 nmol/L bortezomib alone for 48 h, the apoptosis levels of H929 cells were (15. 12±1. 59)%, (18. 23±6. 38)% and (10. 71±1. 62)%, respectively, which were all significantly higher than that of the control group ([6. 46±1. 18]%; P<0. 05, P<0. 01); the apoptosis levels of RPMI8226 cells were (9. 29±1. 44)%, (15. 01±4. 99)% and (7. 58±1. 13)%, respectively, and those of treated with 10 μmol/L ibrutinib and 10 μmol/L AVL-292 were significantly higher than that of the control group ([5. 54±1. 61]%, P<0. 05). The apoptosis levels of H929 cells in the 20 nmol/L bortezomib+10 μmol/L ibrutinib and 20 nmol/L bortezomib+10 μmol/L AVL-292 groups were (40. 31±3. 94)% and (51. 55±6. 39)%, respectively, and those of RPMI8226 cells were (31. 86±1. 93)% and (43. 23±4. 03)%, respectively, and they were all significantly higher than those in their corresponding single agent groups (P<0. 01). Compared with control group, the phosphorylation levels of BTK, NF-κB p65, Akt and ERK and expression of Bcl-xL protein were significantly decreased in H929 cells treated with 10 μmol/L ibrutinib or 10 μmol/L AVL-292 for 24 h (P<0. 05), and the expression of cleaved caspase-3 was significantly increased (P<0. 01). The regulation effects on the above indices were significantly more evident when the two agents were combined with 20 nmol/L bortezomib (P<0. 05, P<0. 01). Conclusion Both ibrutinib and AVL-292 can inhibit proliferation and induce apoptosis of human MM cell lines H929 and RPMI8226; there are significant synergistic effects between them and proteasome inhibitor bortezomib, which may be related to inhibition of BTK activity and the downstream pathways (NF-κB, Akt and ERK), down-regulation of Bcl-xL and activation of caspase-3 apoptotic pathway.