ABSTRACT
Introduction: The aim of this study was to compare the effect of five types of PEGlated nanoliposomes (PNLs) on α-synuclein (α-syn) fibrillization, attenuation of microglial activation, and silence of the SNCA gene, which encodes α-syn. Methods: To evaluate the inhibition of α-syn fibrillization, we used standard in vitro assay based on Thioflavin T (ThT) fluorescence. Next, to evaluate the attenuation of microglial activation, the concentration of TNF-a and IL-6 was quantified by ELISA assay in BV2 microglia cells treated with 100 nM A53T α-syn and PNLs. In order to determine the silencing of the SNCA, real-time PCR and Western blot analysis was used. Finally, the efficacy of PNLs was confirmed in a transgenic mouse model expressing human α-syn.Results: ThT assay showed both PNL1 and PNL2 significantly inhibited a-syn fibrillization. ELISA test also showed the production of TNF-a and IL-6 was significantly attenuated when microglial cells treated with PNL1 or PNL2. We also found that SNCA gene, at both mRNA and protein levels, was significantly silenced when BV2 microglia cells were treated with PNL1 or PNL2. Importantly, the efficacy of PNL1 and PNL2 was finally confirmed in vivo in a transgenic mouse model. Conclusions: In conclusion, the novel multifunctional nanoliposomes tested in our study inhibit α-syn fibrillization, attenuate microglial activation, and silence SNCA gene. Our findings suggest the therapeutic potential of PNL1 and PNL2 for treating synucleinopathies.(AU)
Introducción: El objetivo de este estudio fue comparar el efecto de cinco tipos de nanoliposomas PEGlados (PNL) sobre la fibrilización de la α-sinucleína (α-syn), la atenuación de la activación microglial y el silencio del gen synuclein alpha (SNCA), que codifica α-syn. Métodos: Para evaluar la inhibición de la fibrilización α-syn, utilizamos un ensayo in vitro estándar basado en la fluorescencia de la tioflavina T (ThT). A continuación, para evaluar la atenuación de la activación microglial, se cuantificó la concentración de factor de necrosis tumoral alpha (TNF-a) e interleucina 6 (IL-6)mediante ensayo ELISA en células de microglía BV2 tratadas con 100 nM de α-syn de A53T y PNL. Para determinar el silenciamiento del SNCA, se utilizó reacción en cadena de la polimerasa (PCR) en tiempo real y análisis de Western blot. Finalmente, la eficacia de las PNL se confirmó en un modelo de ratón transgénico que expresa α-syn humana. Resultados: El ensayo ThT mostró que tanto PNL1 como PNL2 inhibieron significativamente la fibrilización de α-syn. La prueba enzyme-linked immunosorbent assay (ELISA) también mostró que la producción de TNF-a e IL-6 se atenuó significativamente cuando las células microgliales se trataron con PNL1 o PNL2. También encontramos que el gen SNCA, tanto a nivel de ARN mensajero (ARNm) como de proteína, se silenciaba significativamente cuando las células de microglía BV2 se trataban con PNL1 o PNL2. Es importante destacar que la eficacia de PNL1 y PNL2 finalmente se confirmó in vivo en un modelo de ratón transgénico.Conclusiones: Los nuevos nanoliposomas multifuncionales probados en nuestro estudio inhiben la fibrilización α-syn, atenúan la activación microglial y silencian el gen SNCA. Nuestros hallazgos sugieren el potencial terapéutico de PNL1 y PNL2 para el tratamiento de sinucleinopatías.(AU)
Subject(s)
Humans , Synucleins , Liposomes , alpha-Synuclein/genetics , Microglia , Disease Models, AnimalABSTRACT
INTRODUCTION: The aim of this study was to compare the effect of five types of PEGlated nanoliposomes (PNLs) on α-synuclein (α-syn) fibrillization, attenuation of microglial activation, and silence of the SNCA gene, which encodes α-syn. METHODS: To evaluate the inhibition of α-syn fibrillization, we used standard in vitro assay based on Thioflavin T (ThT) fluorescence. Next, to evaluate the attenuation of microglial activation, the concentration of TNF-a and IL-6 was quantified by ELISA assay in BV2 microglia cells treated with 100nM A53T α-syn and PNLs. In order to determine the silencing of the SNCA, real-time PCR and Western blot analysis was used. Finally, the efficacy of PNLs was confirmed in a transgenic mouse model expressing human α-syn. RESULTS: ThT assay showed both PNL1 and PNL2 significantly inhibited a-syn fibrillization. ELISA test also showed the production of TNF-a and IL-6 was significantly attenuated when microglial cells treated with PNL1 or PNL2. We also found that SNCA gene, at both mRNA and protein levels, was significantly silenced when BV2 microglia cells were treated with PNL1 or PNL2. Importantly, the efficacy of PNL1 and PNL2 was finally confirmed in vivo in a transgenic mouse model. CONCLUSIONS: In conclusion, the novel multifunctional nanoliposomes tested in our study inhibit α-syn fibrillization, attenuate microglial activation, and silence SNCA gene. Our findings suggest the therapeutic potential of PNL1 and PNL2 for treating synucleinopathies.
Subject(s)
Microglia , alpha-Synuclein , Humans , Animals , Mice , alpha-Synuclein/genetics , Interleukin-6 , Disease Models, Animal , Mice, TransgenicABSTRACT
OBJECTIVE: To evaluate the effects of a prophylactic transfusion program (TP) on obstetric and perinatal outcomes in pregnant women with sickle cell disease (SCD). METHODS: This retrospective cohort study included all singleton pregnancies among women with SCD in a French university tertiary care center between 1 January 2004 and 31 December 2017. The TP group included patients selected according to the French guidelines who received regular red blood cell transfusions during pregnancy until delivery. The factors associated with TP indication [year of birth, SCD genotype, history of acute chest syndrome and delayed hemolysis transfusion reaction (DHTR) risk score] were taken into account in a propensity score. A composite obstetric adverse outcome was defined associating birth before 34 gestational weeks and/or pre-eclampsia and/or small for gestational age and/or abruption and/or stillbirth and/or maternal death and/or neonatal death. RESULTS: In total, 246 pregnancies in 173 patients were analyzed. Twenty-two pregnancies with a history of DHTR were excluded. A higher frequency of TP was found before 2013 [119/148 (80.4%) vs 38/76 (50%); p < 0.001]. Rates of preterm birth before 34 gestational weeks (5.6% vs 19.7%; p = 0.001), vaso-occlusive crisis (36.5% vs. 61.8%; p < 0.001), and acute chest syndrome (6.1% vs. 14.5%; p = 0.04) during pregnancy were decreased significantly in the TP group. Among the groups with and without composite obstetric adverse outcomes, the frequency of TP was 52.6% and 74.7%, respectively [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.09-1.02]. The multivariate analysis shows that the TP was associated with a significant reduction in the risk of composite obstetric adverse outcomes (OR 0.28, 95% CI 0.08-0.97; p = 0.04). CONCLUSION: A red blood cell TP may have an independent protective effect on maternal and perinatal adverse outcomes during pregnancy in women with SCD.
Subject(s)
Acute Chest Syndrome , Anemia, Sickle Cell , Premature Birth , Female , Infant, Newborn , Pregnancy , Humans , Pregnant Women , Acute Chest Syndrome/complications , Retrospective Studies , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/therapy , Stillbirth/epidemiology , Pregnancy OutcomeABSTRACT
Introduction: The expression of specific miRNAs and their mRNA targets are changed in infec-tious disease. The aim of this study was to analyze the expression of pro-neuroinflammatorymiRNAs, anti-neuroinflammatory miRNAs, and their mRNA targets in the serum of COVID-19patients with different grades. Methods: COVID-19 patients with different grades were enrolled in this study and the expres-sion of pro-neuroinflammatory miRNAs, anti-neuroinflammatory miRNAs, and their targetmRNAs was analyzed by q-PCR. Results: The relative expression of anti- neuroinflammatory miRNAs (mir-21, mir-124, and mir-146a) was decreased and the relative expression of their target mRNAs (IL-12p53, Stat3, andTRAF6) was increased. Also, the relative expression of pro-neuroinflammatory miRNAs (mir-326, mir-155, and mir-27b) was increased and the relative expression of their target mRNA(PPARS, SOCS1, and CEBPA) was decreased in COVID-19 patients with increase of disease grade.A negative significant correlation was seen between mir-21 and IL-12p53 mRNA, mir-124 andStat3 mRNA, mir-146a and TRAF6 mRNA, mir-27b and PPARS mRNA, mir-155 and SOCS1 mRNA,and between mir-326 and CEBPA mRNA in COVID-19 patients (P < 0.05). Conclusions: This study showed that the relative expression of anti- neuroinflammatory miRNAswas decreased and the relative expression of their targeted mRNAs was increased in COVID-19 patients from asymptomatic to critical illness. Also, this study showed that the relativeexpression of pro-neuroinflammatory miRNAs was increased and the relative expression of theirtargeted mRNA was decreased in COVID-19 patients from asymptomatic to critical illness.(AU)
Introducción: La expresión de miARN específicos y sus dianas de ARNm se modifican en lasenfermedades infecciosas. El objetivo de este estudio fue analizar la expresión de miARN pro-neuroinflamatorios, miARN anti-neuroinflamatorios y sus ARNm dianas en el suero de pacientescon COVID-19 de diferentes grados. Métodos: Se incluyeron en este estudio pacientes con COVID-19 de diferentes grados y seanalizó la expresión de miARN pro-neuroinflamatorios, miARN anti-neuroinflamatorios y susARNm diana mediante q-PCR. Resultados: La expresión relativa de miARN anti-neuroinflamatorios (mir-21, mir-124 y mir-146a) disminuyó y la expresión relativa de sus ARNm diana (IL-12p53, Stat3 y TRAF6) aumentó.Además, la expresión relativa de miARN pro-neuroinflamatorios (mir-326, mir-155 y mir-27b)aumentó y la expresión relativa de su ARNm diana (PPARS, SOCS1 y CEBPA) disminuyó enpacientes con COVID-19 con aumento del grado de enfermedad. Se observó una correlaciónnegativa significativa entre ARNm de mir-21 e IL-12p53, ARNm de mir-124 y Stat3, ARNm demir-146a y TRAF6, ARNm de mir-27b y PPARS, ARNm de mir-155 y SOCS1, y entre mir-326 yARNm de CEBPA en pacientes con COVID-19 (p < 0,05). Conclusiones: Este estudio mostró que la expresión relativa de miARN anti-neuroinflamatoriosdisminuyó y la expresión relativa de sus ARNm diana se incrementó en pacientes con COVID-19de enfermedad asintomática a crítica. Además, este estudio mostró que la expresión relativade miARN pro-neuroinflamatorios aumentó y la expresión relativa de su ARNm diana disminuyóen pacientes con COVID-19 de enfermedad asintomática a crítica.(AU)
Subject(s)
Humans , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Biomarkers , MicroRNAs , Neurology , Nervous System DiseasesABSTRACT
INTRODUCTION: The expression of specific miRNAs and their mRNA targets are changed in infectious disease. The aim of this study was to analyze the expression of pro-neuroinflammatory miRNAs, anti-neuroinflammatory miRNAs, and their mRNA targets in the serum of COVID-19 patients with different grades. METHODS: COVID-19 patients with different grades were enrolled in this study and the expression of pro-neuroinflammatory miRNAs, anti-neuroinflammatory miRNAs, and their target mRNAs was analyzed by q-PCR. RESULTS: The relative expression of anti- neuroinflammatory miRNAs (mir-21, mir-124, and mir-146a) was decreased and the relative expression of their target mRNAs (IL-12p53, Stat3, and TRAF6) was increased. Also, the relative expression of pro-neuroinflammatory miRNAs (mir-326, mir-155, and mir-27b) was increased and the relative expression of their target mRNA (PPARS, SOCS1, and CEBPA) was decreased in COVID-19 patients with increase of disease grade. A negative significant correlation was seen between mir-21 and IL-12p53 mRNA, mir-124 and Stat3 mRNA, mir-146a and TRAF6 mRNA, mir-27b and PPARS mRNA, mir-155 and SOCS1 mRNA, and between mir-326 and CEBPA mRNA in COVID-19 patients (P<0.05). CONCLUSIONS: This study showed that the relative expression of anti- neuroinflammatory miRNAs was decreased and the relative expression of their targeted mRNAs was increased in COVID-19 patients from asymptomatic to critical illness. Also, this study showed that the relative expression of pro-neuroinflammatory miRNAs was increased and the relative expression of their targeted mRNA was decreased in COVID-19 patients from asymptomatic to critical illness.
Subject(s)
COVID-19 , MicroRNAs , Humans , TNF Receptor-Associated Factor 6/metabolism , Critical Illness , Peroxisome Proliferator-Activated Receptors/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Biomarkers , RNA, Messenger/genetics , RNA, Messenger/metabolism , Patient AcuityABSTRACT
Introduction: The expression of specific miRNAs and their mRNA targets are changed in infectious disease. The aim of this study was to analyze the expression of pro-neuroinflammatory miRNAs, anti-neuroinflammatory miRNAs, and their mRNA targets in the serum of COVID-19 patients with different grades. Methods: COVID-19 patients with different grades were enrolled in this study and the expression of pro-neuroinflammatory miRNAs, anti-neuroinflammatory miRNAs, and their target mRNAs was analyzed by q-PCR. Results: The relative expression of anti- neuroinflammatory miRNAs (mir-21, mir-124, and mir-146a) was decreased and the relative expression of their target mRNAs (IL-12p53, Stat3, and TRAF6) was increased. Also, the relative expression of pro-neuroinflammatory miRNAs (mir-326, mir-155, and mir-27b) was increased and the relative expression of their target mRNA (PPARS, SOCS1, and CEBPA) was decreased in COVID-19 patients with increase of disease grade. A negative significant correlation was seen between mir-21 and IL-12p53 mRNA, mir-124 and Stat3 mRNA, mir-146a and TRAF6 mRNA, mir-27b and PPARS mRNA, mir-155 and SOCS1 mRNA, and between mir-326 and CEBPA mRNA in COVID-19 patients (P < 0.05). Conclusions: This study showed that the relative expression of anti- neuroinflammatory miRNAs was decreased and the relative expression of their targeted mRNAs was increased in COVID-19 patients from asymptomatic to critical illness. Also, this study showed that the relative expression of pro-neuroinflammatory miRNAs was increased and the relative expression of their targeted mRNA was decreased in COVID-19 patients from asymptomatic to critical illness.
Introducción: La expresión de miARN específicos y sus dianas de ARNm se modifican en las enfermedades infecciosas. El objetivo de este estudio fue analizar la expresión de miARN pro-neuroinflamatorios, miARN anti-neuroinflamatorios y sus ARNm dianas en el suero de pacientes con COVID-19 de diferentes grados. Métodos: Se incluyeron en este estudio pacientes con COVID-19 de diferentes grados y se analizó la expresión de miARN pro-neuroinflamatorios, miARN anti-neuroinflamatorios y sus ARNm diana mediante q-PCR. Resultados: La expresión relativa de miARN anti-neuroinflamatorios (mir-21, mir-124 y mir-146a) disminuyó y la expresión relativa de sus ARNm diana (IL-12p53, Stat3 y TRAF6) aumentó. Además, la expresión relativa de miARN pro-neuroinflamatorios (mir-326, mir-155 y mir-27b) aumentó y la expresión relativa de su ARNm diana (PPARS, SOCS1 y CEBPA) disminuyó en pacientes con COVID-19 con aumento del grado de enfermedad. Se observó una correlación negativa significativa entre ARNm de mir-21 e IL-12p53, ARNm de mir-124 y Stat3, ARNm de mir-146a y TRAF6, ARNm de mir-27b y PPARS, ARNm de mir-155 y SOCS1, y entre mir-326 y ARNm de CEBPA en pacientes con COVID-19 (p < 0,05). Conclusiones: Este estudio mostró que la expresión relativa de miARN anti-neuroinflamatorios disminuyó y la expresión relativa de sus ARNm diana se incrementó en pacientes con COVID-19 de enfermedad asintomática a crítica. Además, este estudio mostró que la expresión relativa de miARN pro-neuroinflamatorios aumentó y la expresión relativa de su ARNm diana disminuyó en pacientes con COVID-19 de enfermedad asintomática a crítica.
ABSTRACT
BACKGROUND: Microalgae are attracting much attention as a promising feedstock for renewable energy production, while simultaneously providing environmental benefits. So far, comparison studies for microalgae selection for this purpose were mainly based on data obtained from batch cultures, where the lipid content and the growth rate were the main selection parameters. The present study evaluates the performance of native microalgae strains in semi-continuous mode, considering the suitability of the algal-derived fatty acid composition and the saponifiable lipid productivity as selection criteria for microalgal fuel production. Evaluation of the photosynthetic performance and the robustness of the selected strain under outdoor conditions was conducted to assess its capability to grow and tolerate harsh environmental growth conditions. RESULTS: In this study, five native microalgae strains from Tunisia (one freshwater and four marine strains) were isolated and evaluated as potential raw material to produce biofuel. Firstly, molecular identification of the strains was performed. Then, experiments in semi-continuous mode at different dilution rates were carried out. The local microalgae strains were characterized in terms of biomass and lipid productivity, in addition to protein content, and fatty acid profile, content and productivity. The marine strain Chlorella sp. showed, at 0.20 1/day dilution rate, lipid and biomass productivities of 35.10 mg/L day and 0.2 g/L day, respectively. Moreover, data from chlorophyll fluorescence measurements demonstrated the robustness of this strain as it tolerated extreme outdoor conditions including high (38 °C) and low (10 °C) temperature, and high irradiance (1600 µmol/m2 s). CONCLUSIONS: Selection of native microalgae allows identifying potential strains suitable for use in the production of biofuels. The selected strain Chlorella sp. demonstrated adequate performance to be scaled up to outdoor conditions. Although experiments were performed at laboratory conditions, the methodology used in this paper allows a robust evaluation of microalgae strains for potential market applications.
ABSTRACT
The aim of this study was to investigate the effect of hexagonal selenium nanoparticles modified by SiRNA (HSNM-SiRNA) to inhibit epidermal growth factor receptor (EGFR) signaling in Human non-small-cell lung cancer (NSCLC). After synthesis, HSNM-SiRNA and HSNs were separately exposed to NSCLC cell lines (A549, H1299, H520, and H1975), and incubated for 6 h at 37 °C. Next, the expression of NFKB, MYC, STAT, ELK1, and GAPDH was evaluated by western blot and real-time PCR. The percentage of apoptotic cells and cell cycle progression were measured when exposed to HSNM-SiRNA and HSNs. Both western blot and real-time PCR results showed that HSNM-SiRNA could down-regulate the expression of all EGFR signaling genes. The percentage of apoptotic cells was significantly increased in all cell lines when exposed to HSNM-SiRNA (P>0.05). HSNM-SiRNA in A549 and H1299 cells significantly increased the proportion of cells in G1/G0 phase and significantly decreased the proportion of cells in S phase.
Subject(s)
ErbB Receptors/genetics , ErbB Receptors/metabolism , Metal Nanoparticles , RNA, Small Interfering/genetics , Selenium , Signal Transduction , Apoptosis/genetics , Base Composition , Biomarkers , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Cycle/genetics , Cell Line, Tumor , ErbB Receptors/chemistry , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Models, Molecular , Molecular Conformation , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/chemistryABSTRACT
The aim of this study was to evaluate an engineered nanostructure to silence five important oncogenes, including BAG1, MDM2, Bcl-2, BIRC5 (survivin) and XIAP, in acute myeloid leukemia subtype 2 (AML-M2). The smart nanostructures were functionalized gold nanoparticles (FGNs) containing five antisense oligonucleotides (AOs) and one anti-CD33(+)/CD34(+) aptamer. First, the best AO for each gene was selected with the OligoWalk online software, and then different arrangements of AOs were evaluated with the RNAstructure software. Thereafter, naked gold nanoparticles (NGNs) were synthesized by the reaction of 1000 mm HAuCl4 with 10 µg ml(-1) ascorbic acid. Next, five AOs and one anti-CD33(+)/CD34(+) aptamer were attached to NGNs through serial reactions. Later, 5 ml of heparinized blood samples from five AML-M2 patients were prepared, cancerous cells were isolated and then incubated with three concentrations (75, 150 and 300 µg ml(-1)) each of FGNs, NGNs, gold nanoparticles functionalized with scrambled oligonucleotides (GNFSONs) and doxorubicin. Finally, cell death percentage and gene expressions were measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and real-time PCR, respectively. This study showed that FGNs and doxorubicin led to more cell death compared with NGNs and GNFSONs (P<0.05). Interestingly, all concentrations of FGNs led to a decrease in gene expression. As an important finding, although all concentrations of doxorubicin could also inhibit the expression of genes, FGNs had more effect (P<0.05). Moreover, both NGNs and GNFSONs could silence all genes only at a concentration of 300 µg ml(-1). For BCL2 and XIAP, a dose-dependent pattern was observed, but there was no similar pattern for others.
Subject(s)
Antigens, CD34/genetics , Aptamers, Nucleotide/genetics , Gene Expression , Leukemia, Myeloid, Acute/genetics , Metal Nanoparticles , Oligonucleotides, Antisense/genetics , Sialic Acid Binding Ig-like Lectin 3/genetics , Antineoplastic Agents/pharmacology , Aptamers, Nucleotide/administration & dosage , Aptamers, Nucleotide/chemistry , Biomarkers, Tumor , Cell Line, Tumor , Gold , Humans , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Oligonucleotides, Antisense/administration & dosage , Oligonucleotides, Antisense/chemistryABSTRACT
This paper focuses on the selection of native microalgae strains suitable for wastewater treatment and biofuel production. Four Chlorophyceae strains were isolated from North-eastern Tunisia. Their performances were compared in continuous mode at a 0.3 1/day dilution rate. The biomass productivity and nutrient removal capacity of each microalgae strain were studied. The most efficient strain was identified as Scenedesmus sp. and experiments at different dilution rates from 0.2 to 0.8 1/day were carried out. Maximal biomass productivity of 0.9 g/L day was obtained at 0.6 1/day. The removal of chemical oxygen demand (COD), ammonium and phosphorus was in the range of 92-94%, 61-99% and 93-99%, respectively. Carbohydrates were the major biomass fraction followed by lipids and then proteins. The saponifiable fatty acid content was in the 4.9-13.2% dry biomass range, with more than 50% of total fatty acids being composed of saturated and monosaturated fatty acids.
Subject(s)
Biofuels , Microalgae/metabolism , Scenedesmus/metabolism , Wastewater/chemistry , Water Purification/methods , Biological Oxygen Demand Analysis , Biomass , Fatty Acids/metabolism , Phosphorus/analysisABSTRACT
BACKGROUND: Nanoparticles have become one of the leading technologies over the past two years. The extensive use of nanoparticles has raised great concern about their occupational fate and biological effects. With an increase in the production and use of nanomaterial, it is more likely to get exposed to them occupationally and environmentally. OBJECTIVE: To assess the toxicity of silver nanoparticles on human mononuclear cells. METHODS: In this in vitro experimental study, suspensions of blood mononuclear cells from 10 young healthy men were incubated with 10-nm silver nanoparticles in different concentrations (range: 1-500 µg/mL) for 6 and 24 hours by MTT assay. Positive and negative controls were used for comparison. RESULTS: After 6 hours of exposure, 10.9% to 48.4% of the cells died. After 24 hours of exposure, the rate ranged from 56.8% to 86.3%. Regardless of the exposure time, the maximum cytotoxicity was observed at the concentration of 500 µg/mL of silver nanoparticles. By increasing the exposure time to 24 hours, the cytotoxicity of nanoparticles substantially increased at all concentrations. Cell death was significantly higher when compared to the controls (p<0.01). CONCLUSION: Silver nanoparticles possess both time- and dose-dependent cytotoxicity and can thus be considered as very toxic for mononuclear cells.
Subject(s)
Leukocytes, Mononuclear/drug effects , Nanoparticles/toxicity , Occupational Exposure/adverse effects , Silver/toxicity , Adult , Cell Death/drug effects , Dose-Response Relationship, Drug , Humans , In Vitro Techniques , MaleABSTRACT
OBJECTIVE: To assess the efficacy of spinal clonidine combined with bupivacaine and sufentanil and its effects on maternal and foetal outcome. STUDY DESIGN: Prospective double-blind randomized study. PATIENTS AND METHODS: One hundred and five patients requesting labour analgesia had combined spinal epidural analgesia with intrathecal bupivacaine 2.5 mg and were randomly assigned to receive in addition either sufentanil 5 microg (S5), sufentanil 5 microg and clonidine 30 microg (C30), or sufentanil 10 microg (S10). Onset time, duration of analgesia, visual analogue scores, blood pressure, ephedrine requirements, heart rate, nausea, pruritus, sedation, motor block, foetal heart rate abnormalities, mode of delivery and Apgar scores were recorded. RESULTS: Mean duration of spinal analgesia was significantly longer in patients receiving spinal clonidine compared to patients in S5 group (144+/-61 min versus 95+/-37 min). The onset time of analgesia was significantly shorter in S10 group (3+/-1 min) versus C30 group (4+/-1 min) and S5 group (4+/-1 min) (P=0.002). Hypotension was significantly more frequent in C30 group (29 versus 3% and 3% in S5 and S10 groups) (p=0,001). Foetal heart rate abnormalities and sedation were also significantly more frequent in C30 group. Mode of delivery (spontaneous, instrumental or caesarean delivery) and Apgar scores were unaffected by clonidine treatment. CONCLUSION: Intrathecal clonidine 30 mug prolongs analgesia. However, it increases the incidence of hypotension, and abnormal foetal heart rate patterns. Thus, this study confirms that the use of 30 mug intrathecal clonidine for labour analgesia is not recommended.
Subject(s)
Analgesics/therapeutic use , Clonidine/adverse effects , Clonidine/therapeutic use , Heart Rate, Fetal/drug effects , Hypotension/chemically induced , Labor, Obstetric/physiology , Analgesics/administration & dosage , Analgesics/adverse effects , Anesthesia, Spinal/methods , Bupivacaine/administration & dosage , Bupivacaine/therapeutic use , Clonidine/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , Injections, Spinal , Labor, Obstetric/drug effects , Pregnancy , Prospective Studies , Sufentanil/administration & dosage , Sufentanil/therapeutic use , Time FactorsABSTRACT
Cutaneous manifestations in renal transplant recipients are frequently represented by infections and cancerous lesions. However, dermatologic lesions secondary to autoimmune diseases are rare. We report a case of pustular psoriasis occurring after renal transplantation in a 31-year-old woman with a history of vitiligo. The patient was on hemodialysis for 2 years for undetermined chronic nephropathy. She received an HLA identical live related transplant from her brother. She was maintained on an immunosuppressive regimen of corticosteroids, azathioprine, and cyclosporine, which was replaced with mycophenolate mofetil because of neurotoxicity and azathioprine was stopped. Thirty-one months after renal transplantation, she developed pustular psoriasis which was treated with retinoids; she experienced a relapse and resistance to treatment despite the reintroduction of cyclosporine.
Subject(s)
Kidney Transplantation/adverse effects , Psoriasis/diagnosis , Adult , Female , Humans , Postoperative Complications/diagnosis , Recurrence , Skin Diseases/epidemiology , Vitiligo/diagnosisSubject(s)
Analgesia, Epidural , Analgesia, Obstetrical , Labor, Obstetric , Patient Satisfaction , Adult , Analgesia, Epidural/adverse effects , Analgesia, Epidural/methods , Anesthetics, Local/therapeutic use , Bupivacaine/therapeutic use , Female , Health Care Surveys , Humans , Pregnancy , Pregnancy Outcome , Risk FactorsABSTRACT
A retrospective study of 24 cases of systemic candidosis observed in a polyvalent intensive care unit over a 6.5 yr period (1987-1993) led to some constatations: an increasingly high incidence of this type of septicaemia (up to 27.5% of all septicaemias), large responsibility of skin saprophytes Candida ( > 62% vs 21% from intestinal Candida albicans), frequent diagnostic difficulties, and a fatal outcome in 7/24 patients (mainly from severe causal illness). In order to improve the prognosis, a more systematic and often empirical resort to fungicidal agents could be justified whenever patients with very severe surgical or medical conditions develop a protracted fever of unclear origin.
