利用无机抗菌剂研制抗菌自酸蚀处理剂的初步研究

目的评价利用无机抗菌剂研制抗菌自酸蚀处理剂的初步可行性。方法将6种无机抗菌剂以0.5% w/v和2.5% w/v的浓度分别加入自行研制的实验自酸蚀处理剂ESP中,进行变形链球菌体外药敏试验。并应用添加了抗菌剂的ESP制备黏结样本,测试无机抗菌剂的添加对材料固化后抗菌活性的影响。结果 ESP本身就具有一定的抗菌作用,在其中添加龙贝无机抗菌粉体或氧化锌晶须复合抗菌剂AT-83可使液体状态下ESP的最小抑菌浓度和最小杀菌浓度显著降低;加入受试的无机抗菌剂使材料固化后的抗菌活性显著增强,其中添加氧化锌晶须复合抗菌剂AT-83的效果最为显著。结论从抗菌性能方面证实了利用受试的无机抗菌剂研制抗菌自酸蚀处理剂的初步可行性。

Induction of antiproliferative effect by diosgenin through activation of p53, release of apoptosis-inducing factor (AIF) and modulation of caspase-3 activity in different human cancer cells

Previously, we demonstrated that a plant steroid, diosgenin, altered cell cycle distribution and induced apoptosis in the human osteosarcoma 1547 cell line. The objective of this study was to investigate if the antiproliferative effect of diosgenin was similar for different human cancer cell lines such as laryngocarcinoma HEp-2 and melanoma M4Beu cells. Moreover, this work essentially focused on the mitochondrial pathway. We found that diosgenin had an important and similar antiproliferative effect on different types of cancer cells. In addition, our new results show that diosgenininduced apoptosis is caspase-3 dependent with a fall of mitochondrial membrane potential, nuclear localization of AIF and poly (ADP-ribose) polymerase cleavage. Diosgenin treatment also induces p53 activation and cell cycle arrest in the different cell lines studied.

The IKK-related kinases： from innate immunity to oncogenesis

Over the past four years, the field of the innate immune response has been highly influenced by the discovery of the IKB kinase （IKK）-related kinases, TANK Binding Kinase I （TBK1） and IKKi, which regulate the activity of interferon regulatory factor （IRF）-3/IRF-7 and NF-κB transcription factors. More recently, additional essential components of the signaling pathways that activate these IKK homologues have been discovered. These include the RNA helicases RIGi and MDA5, and the downstream mitochondrial effector known as CARDIF/MAVS/VISA/IPS-1. In addition to their essential functions in controlling the innate immune response, recent studies have highlighted a role of these kinases in cell proliferation and oncogenesis. The canonical IKKs are well recognized to be a bridge linking chronic inflammation to cancer. New findings now suggest that the IKK-related kinases TBK1 and IKKi also participate in signaling pathways that impact on cell transformation and tumor progression. This review will therefore summarize and discuss the role of TBK1 and IKKi in cellular transformation and oncogenesis by focusing on their regulation and substrate specificity.

Long-term stability of gentamicin sulfate-ethylenediaminetetraacetic acid disodium salt (EDTA-Na_2) solution for catheter locks

A lock solution composed of gentamicin sulfate(5 mg/mL) and ethylenediaminetetraacetic acid disodium salt(EDTA-Na2, 30 mg/mL) could fully eradicate in vivo bacterial biofilms in totally implantable venous access ports(TIVAP). In this study, fabrication, conditioning and sterilization processes of antimicrobial lock solution(ALS) were detailed and completed by a stability study. Stability of ALS was conducted for12 months in vial(25 °C 7 2 °C, 60% 7 5% relative humidity(RH), and at 40 °C 7 2 °C, RH 75% 7 5%)and for 24 h and 72 h in TIVAP(40 °C 7 2 °C, RH 75% 7 5%). A stability indicating HPLC assay with UV detection for simultaneous quantification of gentamicin sulfate and EDTA-Na2 was developed. ALS was assayed by ion-pairing high performance liquid chromatography(HPLC) needing gentamicin derivatization, EDTA-Na2 metallocomplexation of samples and gradient mobile phase. HPLC methods to separate four gentamicin components and EDTA-Na2 were validated. Efficiency of sterility procedure and conditioning of ALS was confirmed by bacterial endotoxins and sterility tests. Physicochemical stability of ALS was determined by visual inspection, osmolality, pH, and sub-visible particle counting. Results confirmed that the stability of ALS in vials was maintained for 12 months and 24 h and 72 h in TIVAP.

Anti-inflammatory and analgesic activities with gastroprotective effect of semi-purified fractions and isolation of pure compounds from Mediterranean gorgonian Eunicella singularis

Objective: To explore anti-inflammatory activities of organic extract and its semi-purified fractions(ethanol, acetone, methanol/dichloromethane) from the Mediterranean gorgonian Eunicella singularis. Methods: The anti-inflammatory and analgesic activities were evaluated, using the carrageenan-induced rat paw edema model and the acetic acid writhing test in mice. The gastroprotective activity was determined using HCl/Et OH induced gastric ulcers in rats. The purification and structure elucidation of compound(s) from the more effective fraction were determined by chromatographic and spectroscopic methods and in comparison with data reported in the literature. Results: The fraction F-Et OH showed an important antiinflammatory activity associated with significant analgesic and gastroprotective properties. The purification and structure elucidation of compound(s) from this fraction lead to the identification of one diterpenoid and four sterols. Conclusions: These results suggested that components from the active fraction can be used to treat various anti-inflammatory diseases.

Formulation, stability testing, and analytical characterization of melatonin-based preparation for clinical trial

A new institutional clinical trial assessed the improvement of sleep disorders in 40 children with autism treated by immediate-release melatonin formulation in different regimens(0.5 mg, 2 mg, and 6 mg daily) for one month. The objectives of present study were to(i) prepare low-dose melatonin hard capsules for pediatric use controlled by two complementary methods and(ii) carry out a stability study in order to determine a use-bydate. Validation of preparation process was claimed as ascertained by mass uniformity of hard capsules.Multicomponent analysis by attenuated total reflectance Fourier transformed infrared(ATR-FTIR) of melatonin/microcrystalline cellulose mixture allowed to identify and quantify relative content of active pharmaceutical ingredients and excipients. Absolute melatonin content analysis by high performance liquid chromatography in 0.5 mg and 6 mg melatonin capsules was 93.6% ± 4.1% and 98.7% ± 6.9% of theoretical value, respectively. Forced degradation study showed a good separation of melatonin and its degradation products. The capability of the method was 15, confirming a risk of false negative < 0.01%. Stability test and dissolution test were compliant over 18 months of storage with European Pharmacopoeia. Preparation of melatonin hard capsules was completed manually and melatonin in hard capsules was stable for 18 months, in spite of low doses of active ingredient. ATR-FTIR offers a real alternative to HPLC for quality control of highdose melatonin hard capsules before the release of clinical batches.

Topical Treatment of Infectious Vaginitis:Effects of Antibiotic,Antifungal and Antiseptic Drugs on the Growth of Normal Vaginal Lactobacillus Strains

Objectives: The balance of the vaginal ecosystem depends on lactobacilli whose biofilm protectsagainst microorganisms that are not normally present or are subdominant in vaginal flora. Vaginal?infection treatments should eliminate pathogens while preserving the?Lactobacillus?flora to prevent relapse or recurrence. The objective of this study was to determine the sensitivity of lactobacilli to antiseptics, antibiotics and antifungal agents used, alone or in combination, in the topical treatment of infectious vaginitis. Materials and Methods: The minimum inhibitory concentration (MIC) of 15 active ingredients and the minimum inhibitory dilution (MID) of 17 pharmaceuticals products were determined for three main?Lactobacillus?strains (L. crispatus,?L. gasseri?and?L. jensenii). Results: The MICs of the antibiotics and antifungal agents were above their critical concentrations in the three strains, contrary to the antiseptics. According to their MID, some pharmaceutical products, especially combinations, inhibit the growth of one or more strains at concentrations that can be found in the vaginal mucosa after application at the usual dosage. Conclusions: Certain topical anti-infective drugs may interfere with the growth of lactobacilli, worsening the vaginal flora imbalance. Maintaining vaginal flora balance should be a selection criterion when choosing an anti-infective therapy.

3种不同维生素D软膏的流变学特征及轻中度银屑病患者的临床舒适度调查

Background: Ointments, classically used for the treatment of dermatological diseases, are monophasic viscous semisolid formulations. According to the proportion of their compounds, they have physicochemical and organoleptic properties and when applied on skin show a specific behaviour allowing to be spread more or less easily. Objective: To measure in vitro rheological characteristics of three vitamin D derivative ointments prescribed for the treatment of psoriasis, and to compare their viscosity and clinical acceptability when applied on the diseased skin. Methods: Rheological characteristics of tacalcitol 4 μ g/g, calcipotriol 50 μ g/g and calcitriol 3 μ g/g ointments were assessed by measuring the oscillatory viscoelastic parameters and the permanent flow analysis. Clinical acceptability was studied in 20 psoriatic male or female subjects, aged 18 years or older. A survey evaluated the acceptability of calcitriol vs. tacalcitol and calcipotriol. Questions included information about fluidity, spreading capacity and stickiness after application. Results: We demonstrated that viscoelastic parameters were four times higher for ointment tacalcitol than for calcipotriol and calcitriol, corresponding to a higher consistency of ointment tacalcitol compared to calcipotriol and calcitriol showing both similar results; better fluidity was demonstrated by calcitriol than by tacalcitol and calcipotriol. Comparable results were obtained for the quality to be spread. The sensation of stickiness, significantly different between tacalcitol and calcitriol, was not different between calcipotriol and calcitriol. Conclusion: The above results confirmthe relationship between rheological in vitro and sensorial in vivo results: variations between different formulations may have an important influence on non-adherence and treatment failure.

Plaque Psoriasis: Understanding Risk Factors of This Inflammatory Skin Pathology

Covering the entire human body, the skin is considered to be one of the most important organs, since it is the first line of protection against chemical and biological external agents. Although the skin protects tissues and organs against external aggression, it can still be unbalanced by various skin diseases, such as psoriasis. This non-contagious inflammatory dermatosis is characterized by the occurrence of erythematous lesions of various sizes covered with whitish scales. This scaling of the skin is the result of a rapid renewal of the epidermis, occurring over five to seven days instead of 28 days. Psoriasis vulgaris, or plaque psoriasis, is the most common form of this disease and is therefore commonly referred to by the term “psoriasis”. This work is a review of the literature on plaque psoriasis, aiming at a better comprehension of the pathology at the histological level, but also to understand the genetic and environmental factors associated with this inflammatory dermatosis.

Production and stability study of a hospital parenteral nutrition solution for neonates

Standard parenteral nutrition solutions are mixtures comprising interacting components that may degrade themselves over time. The objective of this study was to investigate the physicochemical and microbiological stability of a hospital preparation for parenteral nutrition in neonatology. The analyses were performed throughout the storage of the preparations at 2–8 °C(up to 4 months). The extent of stability was based on the determination of amino acids dosage, visual and physicochemical properties(glucose and electrolytes concentrations, pH and osmolality measurements, particle counting) and microbiological analysis(sterility test). A thermal degradation of ascorbic acid was conducted to evaluate the antioxidant properties of the parenteral mixture. Physicochemical and microbiological controls were found to comply with the specifications. Amino acids showed a good stability throughout the 4 months storage except for cysteine, which was progressively degraded to cystine, conferring a yellow coloration to parenteral solutions. Parenteral nutrition standards solutions remain stable for 4 months at 2–8 °C,ensuring safe administration in preterm infants.

Effect of -Lipoic Acid on Proteasomal Induction: Protection against Oxidative Damage in Human Skin Fibroblasts Cell Line NHDF

As human skin is daily exposed to oxidative stress causing various unesthetical abnormalities, the road to effective anti-aging substances is being widely investigated. 20S proteasome is a key pathway in the breakdown of oxidized proteins. But its activity declines dramatically in aging cells. Nrf2 inducers -lipoic acid (LA) and sulforaphane (SFN) have been described in the dietary industries for their antioxidant effects on various cell lines. However, since little is yet known about LA’s capacity to protect skin cells from premature and extrinsic aging;our aim was to demonstrate the beneficial effect of LA on the cellular detoxification systems. On this purpose, we evaluated its effects against injuries induced by H2O2 in NHDF and its likely positive effect on the chymotrypsin-like (CT-like) activity of 20S proteasome, using SFN as a reference. The cellular content in proteins was measured, as well as the production of Reactive Oxygen Species (ROS). Also, the induction of the proteasomal protein expression was investigated. The results show that after 48 h treatment, LA significantly decreased the percentage of ROS positive cells. Also, LA decreased the level of H2O2-induced carbonylated proteins and increased the proteasomal activity. Furthermore, LA upregulated the expression of the 20S proteasome &#223;-subunit responsible for the CT-like activity (PSMB5). Overall, both molecules enhanced cell proliferation over 8 days. So, our investigation found evidence of the higher capacity of LA to induce 20S proteasome activity with less toxicity in human fibroblasts compared to reference molecule SFN. These results tend to demonstrate that the induction of the proteasomal activity might be a part of the antioxidant potential of LA. To our knowledge, this is the first study to elucidate the capacity of LA to activate detoxification systems in human cell lines through the induction of 20S proteasome.

Composition of the Volatile Components Extracted from the Roots of <i>Scorzonera undulata</i>ssp <i>deliciosa</i>(Guiss) Maire: From Algeria

The chemical composition of the volatile components of the dried roots of Scorzonera undulata ssp deliciosa collected from Algeria was determined by GC and GC/MS. The obtained results showed that the extracted oil contained nine fatty acids. The major compounds were hexadecanoic acid (42.2%), n-tetradecanoic acid (16.1%), 9-octadecenoic acid (7.7%) and 9-hexadecenoic acid (4.5%).

Induction of Phase II Enzymes Glutathione-S-Transferase and NADPH: Quinone Oxydoreductase 1 with Novel Sulforaphane Derivatives in Human Keratinocytes: Evaluation of the Intracellular GSH Level

Phase II enzymes including NADPH: Quinone Oxydoreductase 1 (NQO1) and Glutathione-S-Transferase (GST) represents a major and natural cellular protection system against deleterious environmental factors which cause skin damages. Sulforaphane is one of the most popular isothiocyanates found in cruciferous vegetables and known for its cytoprotective effects by inducing Phase II enzymes. Five novel sulforaphane derivatives were synthetized and tested for their activity on NQO1 and GST induction as well as for their effect on total GSH intracellular level using colorimetric assays on human keratinocytes cell line (HaCat). As sulforaphane and the synthetized components showed variable toxicity after their evaluation by means of in vitro cytotoxicity (MTT test), cells were treated at a concentration of 5 μM during 48 hours. The results showed that the addition products of sulforaphane decreased cytotoxity but none of those derivatives had a better effect than referenced sulforaphane on Phase II enzymes. It seems that the isothiacyanate function remains important for the sulforaphane activity.

Novel Cytocidal Substituted Phenyl 4-(2-Oxoimidazolidin-1-yl) Benzenesulfonates and Benzenesulfonamides with Affinity to the Colchicine-Binding Site: Is the Phenyl 2-Imidazolidinone Moiety a New Haptophore for the Design of New Antimitotics?

Phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PIB-SOs) and phenyl 4-(2-oxoimidazolidin- 1-yl)benzenesulfonamides (PIB-SAs) are new, potent combretastatin A-4 (CA-4) analogs designed on the basis of their common phenyl 2-imidazolidone moiety. This phenyl 2-imidazolidone group is a bioisosteric equivalent of the trimethoxyphenyl group also found in colchicine, podophyllotoxin and several other ligands of the colchicine-binding site (C-BS). In this study, we investigate the interactions involved in the binding of PIB-SO and PIB-SA into the C-BS. We describe three distinct pockets (I, II, and III) as key structural elements involved in the interactions between the C-BS and PIB-SOs as well as PIB-SAs. We show that PIB-SOs and PIB-SAs adopt 4 and 3 distinct binding conformations, respectively, within the C-BS. The binding conformations I and IV are common to most PIB-SOs and PIB-SAs exhibiting high affinity for the C-BS and high cytocidal potency. In addition, binding conformation I is the main conformation adopted by PIB-SOs, PIB-SAs, T138067, ABT-751, colchicine and CA-4. We also observe that the sulfonate and the sulfonamide moieties of PIB-SOs and PIB-SAs are bioisosteric equivalents. Interestingly, we further find that a large portion of the phenyl 2-imidazolidinone moiety in these analogs does not bind to pocket I unlike the trimethoxyphenyl moiety found in several antimicrotubule agents such as colchicine, CA-4 and podophyllotoxin, suggesting that the phenyl 2-imidazolidinone group may represent a new haptophoric moiety useful for the design of new C-BS inhibitors mimicking the tropolone and the methoxylated phenolic moieties of colchicine and CA-4, respectively.

HLA-G 3’UTR 14 bp Insertion Is Associated with a Decreased Risk of Developing Human African Trypanosomiasis in the Côte d’Ivoire Population

Human African trypanosomiasis (HAT), or sleeping sickness, caused by Trypanosoma brucei gambiense, is associated with diverse clinical outcomes. Host’s genetic factors involved in immunity are potential factors that can regulate infection. Genetic polymorphisms within HLA-G could influence the level of HLA-G expression and therefore play a critical role in infection outcomes. The goal of our study was to investigate the association of 14 bp Indel HLA-G polymorphism with the susceptibility/resistance to HAT. DNA samples were collected from 119 cases, 221 controls and 43 seropositive individuals living in Ivorian HAT foci. The 14 bp Indel polymorphism was determined by PCR. Homozygous individuals for 14 bp insertion had a lower risk of progressing to active HAT (p = 0.012, OR = 0.27, 95% CI: 0.09 - 0.8). Moreover, the frequency of 14 bp insertion homozygous genotype was higher in the seropositive group (11%) than in the HAT cases group (3%) (p = 0.043, OR = 0.27, 95% CI: 0.07 - 0.99), which suggested a protective effect of 14 bp insertion homozygous genotype. Genetic polymorphisms in HLA-G may be associated with a variable risk to develop HAT. The 14 bp insertion appears to favour the occurrence of long-lasting T. b. gambiense latent infections.

New Method for Injectable Quinine Quality Assurance Control Using a Multi-Spectral Microscope

Africa is the world region that is most affected by malaria. Among the therapies used, injectable quinine is considered to be one of the effective antimalarial drug, however non-quality assured antimalarials clearly have a strong market penetration across Africa. To overcome this problem, it becomes more and more necessary to set up quantitative and qualitative analysis system for antimalarial quality control. The objective of the present investigation is an attempt to use customized multispectral microscope equipped with UV-Visible lasers for injectable quinine quality assurance control routinely. For that, we have established the calibration curve of quinine solution concentration as a function of area under light intensity histogram crossing the solution. From this calibration curve, we can check the conformity of any injectable quinine according to the pharmacopoeia involved. The proposed technique is a promising alternative for drug quality control routinely.

French Validation of the Screen for Cognitive Impairment in Psychiatry (SCIP-F)

Background: Measuring cognition in clinical practice is clearly essential to the appropriate characterisation of patients’ clinical status and to the development of a personalised care plan. The Screen for Cognitive Impairment in Psychiatry (SCIP) has been developed in order to provide a brief and accessible tool allowing the evaluation of cognitive function in psychiatric conditions. Objective: We present a validation of a French version of the SCIP. Method: Translation from English into French is carried out using the accepted back-translation method. Seventy-two healthy volunteers are characterised by demographic questionnaires and a neuropsychological battery. The French version of the SCIP is then administered on two separate occasions separated by at least a one-week interval. Results: High internal consistencies as well as strong correlations with comparable neuropsychological tests are obtained. A normalised Cronbach’s α = 0.66 is obtained. Conclusions: The French version of the SCIP (SCIP-F) yields results comparable to the English version. The SCIP represents an essential tool for the preliminary evaluation of cognition. Its characteristics, brevity and the lack of need for a technological platform, allow for its integration into clinical practice. Further testing of SCIP-F in various psychiatric conditions will yield valuable information on its potential in clinical settings.

Effect of physiological harvest stages on the composition of bioactive compounds in Cavendish bananas

The combined influence of maturation,ripening,and climate on the profile of bioactive compounds was studied in banana(Musa acuminata,AAA,Cavendish,cv.Grande Naine).Their bioactive compounds were determined by the Folin-Ciocalteu assay and high-performance thin layer chromatographic(HPTLC) method.The polyphenol content of bananas harvested after 400 degree days remained unchanged during ripening,while bananas harvested after 600 and 900 degree days exhibited a significant polyphenol increase.Although dopamine was the polyphenol with the highest concentration in banana peels during the green developmental stage and ripening,its kinetics differed from the total polyphenol profile.Our results showed that this matrix of choice(maturation,ripening,and climate) may allow selection of the banana(M.acuminata,AAA,Cavendish,cv.Grande Naine) status that will produce optimal concentrations of identified compounds with human health relevance.