BACKGROUND: Concerns over gadolinium (Gd) retention encourage the use of lower Gd doses. However, lower Gd doses may compromise imaging performance. Higher relaxivity gadobenate may be suited to reduced dose protocols. PURPOSE: To compare 0.05 mmol/kg and 0.1 mmol/kg gadobenate in patients undergoing enhanced MRI of the central nervous system (CNS). STUDY TYPE: Retrospective, multicenter. POPULATION: Three hundred and fifty-two patients receiving 0.05 (n = 181) or 0.1 (n = 171) mmol/kg gadobenate. FIELD STRENGTH/SEQUENCES: 1.5 T and 3.0 T/precontrast and postcontrast T1-weighted spin echo/fast spin echo (SE/FSE) and/or gradient echo/fast field echo (GRE/FFE); precontrast T2-weighted FSE and T2-FLAIR. ASSESSMENT: Images of patients with extra-axial lesions at 1.5 T or any CNS lesion at 3.0 T were reviewed by three blinded, independent neuroradiologists for qualitative (lesion border delineation, internal morphology visualization, contrast enhancement; scores from 1 = poor to 4 = excellent) and quantitative (lesion-to-brain ratio [LBR], contrast-to-noise ratio [CNR]; SI measurements at regions-of-interest on lesion and normal parenchyma) enhancement measures. Noninferiority of 0.05 mmol/kg gadobenate was determined for each qualitative endpoint if the lower limit of the 95% confidence interval (CI) for the difference in precontrast + postcontrast means was above a noninferiority margin of -0.4. STATISTICAL TESTS: Student's t-test for comparison of mean qualitative endpoint scores, Wilcoxon signed rank test for comparison of LBR and CNR values; Wilcoxon rank sum test for comparison of SI changes. Tests were significant for P < 0.05. RESULTS: The mean change from precontrast to precontrast + postcontrast was significant for all endpoints. Readers 1, 2, and 3 evaluated 304, 225, and 249 lesions for 0.05 mmol/kg gadobenate, and 382, 309, and 298 lesions for 0.1 mmol/kg gadobenate. The lower limit of the 95% CI was above -0.4 for all comparisons. Significantly, higher LBR and CNR was observed with the higher dose. DATA CONCLUSION: 0.05 mmol/kg gadobenate was noninferior to 0.1 mmol/kg gadobenate for lesion visualization. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.
- MeSH
- Gadolinium DTPA MeSH
- Contrast Media MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Meglumine analogs & derivatives MeSH
- Brain diagnostic imaging MeSH
- Brain Neoplasms * MeSH
- Organometallic Compounds * MeSH
- Retrospective Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
Bifidobacterium longum, one of the main microorganisms in the human gut, is used as an adjunct to lactic acid starter cultures or sold as a probiotic product. Therefore, Bifidobacterium longum cell suspensions get freeze-dried with protective additives to prevent activity losses. To date, investigations covering growth and inactivation kinetics of Bifidobacterium longum during the whole process (cultivation, drying, and storage) have been lacking. In this study, the effect of cultivation conditions and shelf temperature as well as the influence of protectants (maltodextrin, glucitol, trehalose) at various concentrations on cell survival during freeze-drying was assessed. Drying was followed by a storage at + 4 °C and + 20 °C for 70 days to evaluate inactivation kinetics. The impact of the different factors was assessed by measuring surival rate and residual moisture content at various points of time over the whole process. In parallel cell membrane integrity and glass transition were determined to reveal inactivation effects. Cultivation strategy had a strong influence on survival with a huge potential for process improvement. A pH of 6.0 at the growth optimum of the strain provides better conditions regarding cell survival after drying than free acidification (non-regulated pH conditions). During the drying step, membrane leakage due to the removal of water is the main reason for the inactivation in this process step. In this study, the highest survival of 49% was obtained with cells dried at + 35 °C shelf temperature with an addition of maltodextrin (75% bacterial dry matter, w/w). The results show that Bifidobacterium longum cells are mostly inactivated during drying, whereas storage conditions at + 4 °C with an addition of 75% BDM maltodextrin relative to bacterial dry mass prevent cell loss completely.
- MeSH
- Bifidobacterium longum growth & development MeSH
- Cell Culture Techniques methods MeSH
- Kinetics MeSH
- Hydrogen-Ion Concentration MeSH
- Culture Media chemistry MeSH
- Humans MeSH
- Freeze Drying methods MeSH
- Microbial Viability * MeSH
- Polysaccharides MeSH
- Probiotics MeSH
- Sorbitol MeSH
- Temperature MeSH
- Trehalose MeSH
- Desiccation methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Leishmaniasis is one of the most important parasitic diseases after malaria. The standard treatment of leishmaniasis includes pentavalent antimonials (SbV); however, these drugs are associated with serious adverse effects. There have been very few studies pertaining to their side effects and mechanism of action in the fetus. This investigation examines the effects of meglumine antimoniate (MA) on the survival rate, angiogenesis and cellular apoptosis in the human umbilical vein endothelial cells (HUVECs). HUVECs were treated with varying doses of MA (100-800 μg/ml) for 24, 48 and 72 h and the survival rate was studied by colorimetric assay, flow cytometry, immunocytochemistry, migration (scratch) assay and tube formation assay. The results of quantitative real-time PCR (qPCR) studies indicated that the most important genes involved in presenting angiogenesis included VEGF and its receptors (Kdr and Flt-1), NP1 and Hif-1α genes including the anti-apoptotic gene of Bcl2, were significantly reduced compared to the control group (p < 0.05). In contrast, the most leading genes involved in the phenomenon of apoptosis were P53, Bax, Bak, Apaf-1 and caspases 3, 8 and 9, which were significantly up regulated compared to the control group (p < 0.05).
- MeSH
- Antiprotozoal Agents toxicity MeSH
- Apoptosis drug effects MeSH
- C-Reactive Protein genetics MeSH
- Human Umbilical Vein Endothelial Cells drug effects physiology MeSH
- Hypoxia-Inducible Factor 1, alpha Subunit genetics MeSH
- Neovascularization, Physiologic drug effects MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Meglumine Antimoniate toxicity MeSH
- Tumor Suppressor Protein p53 genetics MeSH
- Cell Movement drug effects MeSH
- Nerve Tissue Proteins genetics MeSH
- Apoptosis Regulatory Proteins genetics MeSH
- Vascular Endothelial Growth Factor A genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Currently, there is no satisfactory treatment modality available for cutaneous leishmaniasis (CL). The major objective of the present study was to explore the effect of immunomodulator-levamisole in combination with Glucantime in end-stage unresponsive patients with anthroponotic CL (ACL). Twenty end-stage unresponsive patients with ACL were identified for participation in this single-group trial study. Simultaneously, each patient was received a combination of levamisole pills along with Glucantime during the remedy course. Several in vitro complementary experiments were performed to evaluate the mode of action of levamisole and Glucantime alone and in combination using a macrophage model, in vitro MTT assay, flow cytometry and quantitative real time PCR (qPCR). Overall, 75% of the patients showed complete clinical cure, 10% partially improved and the remaining (15%) had underlying chronic diseases demonstrated no response to the treatment regimen. In in vitro studies, there was no cytotoxic effect associated with these drugs in the range of our experiments. The findings by the flow cytometric analysis represented that the highest apoptotic values corresponded to the drugs combination (32.23%) at 200 μg/ml concentration. Finally, the gene expression level of IL-12 p40, iNOS and TNF-α promoted while the level of IL-10 and TGF-β genes reduced as anticipated. The findings clearly indicated that the combination of levamisole and Glucantime should be considered in end-stage unresponsive patients with ACL who have not responded to basic treatments. The immunomodulatory role of levamisole in mounting immune system as documented by the in vitro experiments and further substantiated by this single-group trail study was highlighted.
- MeSH
- Antiprotozoal Agents pharmacology therapeutic use MeSH
- Cell Line drug effects MeSH
- Chronic Disease therapy MeSH
- Child MeSH
- Adult MeSH
- Drug Combinations MeSH
- Interleukin-10 metabolism MeSH
- Interleukin-12 Subunit p40 metabolism MeSH
- Drug Therapy, Combination MeSH
- Leishmania tropica drug effects pathogenicity MeSH
- Leishmaniasis, Cutaneous drug therapy MeSH
- Levamisole administration & dosage pharmacology therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Macrophages drug effects MeSH
- Meglumine Antimoniate administration & dosage pharmacology therapeutic use MeSH
- Adolescent MeSH
- Young Adult MeSH
- Mice MeSH
- Aged MeSH
- Nitric Oxide Synthase Type II metabolism MeSH
- Tumor Necrosis Factor-alpha metabolism MeSH
- Transforming Growth Factor beta metabolism MeSH
- Cell Survival drug effects MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Mice MeSH
- Aged MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The control of cutaneous leishmaniasis (CL) is facilitated by knowledge of factors associated with the treatment failures in endemic countries. The aim of this evaluation was to identify the potential risk determinants which might affect the significance of demographic and clinical characteristics for the patients with anthroponotic CL (ACL) and the outcome of meglumine antimoniate (MA) (Glucantime) treatment. METHODOLOGY/PRINCIPAL FINDINGS: This current was executed as a cohort spanning over a period of 5 years which centered in southeastern part of Iran. Altogether, 2,422 participants were evaluated and 1,391 eligible volunteer patients with ACL caused by Leishmania tropica were included. Overall, 1,116 (80.2%) patients received MA intraleisionally (IL), once a week for 12 weeks along with biweekly cryotherapy, while 275 (19.8%) patients received MA alone (20 mg/kg/day for 3 weeks) (intramuscular, IM). The treatment failure rate in ACL patients was 11% using IL combined with cryotherapy plus IM alone, whilst 9% and 18.5% by IL along with cryotherapy or IM alone, respectively. Multivariate logistic regression model predicted 5 major associated-risk determinants including male (odds ratio (OR) = 1.54, confidence interval (CI) = 1.079-2.22, p = 0.018), lesion on face (OR = 1.574, CI = 1.075-2.303, p = 0.02), multiple lesions (OR = 1.446, CI = 1.008-2.075, p = 0.045), poor treatment adherence (OR = 2.041, CI = 1.204-3.46, p = 0.008) and disease duration > 4 months (OR = 2.739, CI = 1.906-3.936, p≤0.001). CONCLUSIONS/SIGNIFICANCE: The present study is the original and largest cohort of ACL patients who treated with MA. A comprehensive intervention and coordinated action by the health authorities and policy-makers are crucial to make sure that patients strictly follow medical instructions. Early detection and effective therapy < 4 months following the onset of the lesion is critical for successful treatment of the patients. Since a significant number of patients are still refractory to MA, reducing man-vector exposure and development of new effective alternative drugs are essential measures against ACL due to L. tropica.
- MeSH
- Antiprotozoal Agents therapeutic use MeSH
- Child MeSH
- Adult MeSH
- Cohort Studies MeSH
- Infant MeSH
- Cryotherapy methods MeSH
- Leishmania tropica isolation & purification MeSH
- Leishmaniasis, Cutaneous drug therapy epidemiology microbiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Meglumine Antimoniate therapeutic use MeSH
- Adolescent MeSH
- Young Adult MeSH
- Treatment Failure MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Iran MeSH
Glucose-6-phosphate dehydrogenase (G6PD) deficiency can present a diagnostic dilemma owing to the varying degrees of disease severity and the wide range of precipitating factors. Here, we report a case of a 56-year-old man who presented with signs and symptoms of heart failure and, during the course of treatment, developed intravascular hemolysis. On investigation, he was found to be G6PD deficient. Following discontinuation of the fixed-dose combination of isosorbide dinitrate and hydralazine, the clinical condition of the patient improved, and there were no further episodes of hemolysis. The case highlights the need for a high degree of suspicion of G6PD deficiency in patients with unexplained signs and symptoms of intravascular hemolysis.
- MeSH
- Drug Combinations MeSH
- Hemolysis drug effects MeSH
- Hydralazine adverse effects MeSH
- Isosorbide Dinitrate adverse effects MeSH
- Cardiovascular Agents adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Glucosephosphate Dehydrogenase Deficiency chemically induced diagnosis MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
During plant growth and defense, cell cycle activity needs to be coordinated with cell wall integrity. Little is known about how this coordination is achieved. Here, we investigated coordination in Arabidopsis thaliana seedlings by studying the impact of cell wall damage (CWD, caused by cellulose biosynthesis inhibition) on cytokinin homeostasis, cell cycle gene expression and cell shape in root tips. CWD inhibited cell cycle gene expression and increased transition zone cell width in an osmosensitive manner. These results were correlated with CWD-induced, osmosensitive changes in cytokinin homeostasis. Expression of CYTOKININ OXIDASE/DEHYDROGENASE 2 and 3 (CKX2, CKX3), which encode cytokinin-degrading enzymes, was induced by CWD and reduced by osmoticum treatment. In nitrate reductase1 nitrate reductase2 (nia1 nia2) seedlings, CKX2 and CKX3 transcript levels were not increased and cell cycle gene expression was not repressed by CWD. Moreover, established CWD-induced responses, such as jasmonic acid, salicylic acid and lignin production, were also absent, implying a central role of NIA1/2-mediated processes in regulation of CWD responses. These results suggest that CWD enhances cytokinin degradation rates through a NIA1/2-mediated process, leading to attenuation of cell cycle gene expression.
- MeSH
- Arabidopsis cytology drug effects genetics MeSH
- Benzamides pharmacology MeSH
- Models, Biological MeSH
- Cell Wall drug effects metabolism MeSH
- Cell Cycle drug effects genetics MeSH
- Cytokinins pharmacology MeSH
- Phenotype MeSH
- Homeostasis drug effects MeSH
- Plant Roots cytology drug effects growth & development MeSH
- RNA, Messenger genetics metabolism MeSH
- Nitrate Reductase metabolism MeSH
- Osmosis MeSH
- Arabidopsis Proteins metabolism MeSH
- Gene Expression Regulation, Plant * drug effects MeSH
- Seedlings drug effects genetics MeSH
- Sorbitol pharmacology MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
In the previous study, the artichoke leaf extract showed effective inhibition of AKR1B1, the first enzyme of polyol pathway, which reduces high level of glucose to osmotically active sorbitol, important for development of chronic diabetic complications. In the present study, the effect of artichoke leaf extract and of several participating phenols (caffeic acid, chlorogenic acid, quinic acid, and luteolin) was tested on sorbitol level in rat lenses exposed to high glucose ex vivo, on cytotoxicity as well as on oxidative stress in C2C12 muscle cell line induced by high glucose in vitro. The concentration of sorbitol was determined by enzymatic analysis, the cytotoxicity was provided by WST-1 test and intracellular content of reactive oxygen species was determined by fluorescence of 2'-7'-dichlorofluorescein probe. The extract and the compounds tested showed significant protection against toxic effects of high concentration of glucose in both models. On balance, the artichoke leaf extract thus represents a prospective preventive agent of development of chronic diabetic complications, probably due to phenols content, concerning preclinical and clinical studies.
- MeSH
- Aldehyde Reductase antagonists & inhibitors MeSH
- Cynara scolymus chemistry MeSH
- Glucose pharmacology MeSH
- Enzyme Inhibitors pharmacology MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Plant Leaves chemistry MeSH
- Mice MeSH
- Lens, Crystalline drug effects metabolism MeSH
- Organ Culture Techniques MeSH
- Oxidative Stress drug effects MeSH
- Reactive Oxygen Species pharmacology MeSH
- Plant Extracts pharmacology MeSH
- Sorbitol metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Good flow and compaction properties are necessary for the manipulation of particulate material in the pharmaceutical industry. The influence of the addition of an alternative sweetener, rebaudioside A, in a concentration 0.2% w/w and 0.5% w/w on the flow, shear and compaction properties of sorbitol for direct compaction, Merisorb® 200, was investigated in this work. Rebaudioside A worsened the flow properties of sorbitol: the Hausner ratio, the compressibility index and the mass flow rate through the aperture of a model hopper. Using a Jenike shear cell revealed a significant increase in cohesion leading to the decrease of the flow function; moreover, the addition of rebaudioside A increased the total energy for compression of tablets and plasticity estimated by the force-displacement method. Finally, the tablets showed a higher tensile strength and needed longer time to disintegrate compared to the tablets made of sorbitol itself. In view of the results for the free-flowable excipient, sorbitol, the effects of stevia even for a 0.2% w/w concentration have to be carefully considered, particularly whenever used in pharmaceutical formulations of poor flow properties.
- MeSH
- Diterpenes, Kaurane chemistry MeSH
- Technology, Pharmaceutical methods MeSH
- Tensile Strength MeSH
- Excipients chemistry MeSH
- Drug Compounding methods MeSH
- Sweetening Agents chemistry MeSH
- Sorbitol chemistry MeSH
- Stevia chemistry MeSH
- Tablets chemistry MeSH
- Pressure MeSH
- Publication type
- Journal Article MeSH
