Sorbitol metabolism plays multiple roles in many plants, including energy and carbon enrichment, effective defence against various stresses and other emerging specific roles. The underlying mechanisms are, however, incompletely understood. This review provides the current state-of-the-art, highlights missing knowledge and poses several remaining questions. The basic properties of sugar alcohols are summarised and pathways of sorbitol metabolism, including biosynthesis, degradation and key enzymes are described. Sorbitol transport within the plant body is discussed and individual roles of sorbitol in different organs, specific cells or even cellular compartments, are elaborated, clarifying the critical importance of sorbitol allocation and distribution. In addition to plants that accumulate and transport significant quantities of sorbitol (usual producers), there are some that synthesize small amounts of sorbitol or only possess sorbitol metabolising enzymes (non-usual producers). Modern analytical methods have recently enabled large amounts of data to be acquired on this topic, although numerous uncertainties and questions remain. For a long time, it has been clear that enriching carbohydrate metabolism with a sorbitol branch improves plant fitness under stress. Nevertheless, this is probably valid only when appropriate growth and defence trade-offs are ensured. Information on the ectopic expression of sorbitol metabolism genes has contributed substantially to our understanding of the sorbitol roles and raises new questions regarding sorbitol signalling potential. We finally examine strategies in plants producing sorbitol compared with those producing mannitol. Providing an in-depth understanding of sugar alcohol metabolism is essential for the progress in plant physiology as well as in targeted, knowledge-based crop breeding.
- Klíčová slova
- Carbohydrate metabolism, Mannitol, Polyols, Reactive oxygen species, Stress, Sugar alcohols,
- MeSH
- cukerné alkoholy * metabolismus MeSH
- mannitol metabolismus MeSH
- metabolismus sacharidů MeSH
- sorbitol * MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- cukerné alkoholy * MeSH
- mannitol MeSH
- sorbitol * MeSH
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.
- Klíčová slova
- GBCA safety, comparative studies, contrast efficacy, gadobenate dimeglumine,
- MeSH
- diethylentriaminpentaacetát gadolinia MeSH
- kontrastní látky MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- meglumin analogy a deriváty MeSH
- mozek diagnostické zobrazování MeSH
- nádory mozku * MeSH
- organokovové sloučeniny * MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- diethylentriaminpentaacetát gadolinia MeSH
- gadobenic acid MeSH Prohlížeč
- kontrastní látky MeSH
- meglumin MeSH
- organokovové sloučeniny * 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.
- Klíčová slova
- Bifidobacterium longum ssp. longum Reuter 1963, Maltodextrin, Membrane preservation, Probiotics, Protectants, Storage temperature,
- MeSH
- Bifidobacterium longum růst a vývoj MeSH
- buněčné kultury metody MeSH
- kinetika MeSH
- koncentrace vodíkových iontů MeSH
- kultivační média chemie MeSH
- lidé MeSH
- lyofilizace metody MeSH
- mikrobiální viabilita * MeSH
- polysacharidy MeSH
- probiotika MeSH
- sorbitol MeSH
- teplota MeSH
- trehalosa MeSH
- vysoušení metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kultivační média MeSH
- maltodextrin MeSH Prohlížeč
- polysacharidy MeSH
- sorbitol MeSH
- trehalosa 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.
- Klíčová slova
- G6PD deficiency, hydralazine, intravascular hemolysis, isosorbide dinitrate,
- MeSH
- fixní kombinace léků MeSH
- hemolýza účinky léků MeSH
- hydralazin škodlivé účinky MeSH
- isosorbiddinitrát škodlivé účinky MeSH
- kardiovaskulární látky škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- nedostatek glukóza-6-fosfátdehydrogenázy chemicky indukované diagnóza MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- fixní kombinace léků MeSH
- hydralazin MeSH
- isosorbiddinitrát MeSH
- isosorbide-hydralazine combination MeSH Prohlížeč
- kardiovaskulární látky 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
- antiprotozoální látky terapeutické užití MeSH
- dítě MeSH
- dospělí MeSH
- kohortové studie MeSH
- kojenec MeSH
- kryoterapie metody MeSH
- Leishmania tropica izolace a purifikace MeSH
- leishmanióza kožní farmakoterapie epidemiologie mikrobiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- meglumin antimoniát terapeutické užití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- neúspěšná terapie MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Írán epidemiologie MeSH
- Názvy látek
- antiprotozoální látky MeSH
- meglumin antimoniát 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).
- Klíčová slova
- Angiogenesis, Apoptosis, HUVECs, Meglumine antimoniate, Toxicity,
- MeSH
- antiprotozoální látky toxicita MeSH
- apoptóza účinky léků MeSH
- C-reaktivní protein genetika MeSH
- endoteliální buňky pupečníkové žíly (lidské) účinky léků fyziologie MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa genetika MeSH
- fyziologická neovaskularizace účinky léků MeSH
- kultivované buňky MeSH
- lidé MeSH
- meglumin antimoniát toxicita MeSH
- nádorový supresorový protein p53 genetika MeSH
- pohyb buněk účinky léků MeSH
- proteiny nervové tkáně genetika MeSH
- proteiny regulující apoptózu genetika MeSH
- vaskulární endoteliální růstový faktor A genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiprotozoální látky MeSH
- C-reaktivní protein MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
- meglumin antimoniát MeSH
- nádorový supresorový protein p53 MeSH
- neuronal pentraxin MeSH Prohlížeč
- proteiny nervové tkáně MeSH
- proteiny regulující apoptózu MeSH
- vaskulární endoteliální růstový faktor A MeSH
- VEGFA protein, human MeSH Prohlížeč
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.
- Klíčová slova
- Cutaneous leishmaniasis, End-stage patients, Glucantime, Levamisole, Treatment,
- MeSH
- antiprotozoální látky farmakologie terapeutické užití MeSH
- buněčné linie účinky léků MeSH
- chronická nemoc terapie MeSH
- dítě MeSH
- dospělí MeSH
- fixní kombinace léků MeSH
- interleukin-10 metabolismus MeSH
- interleukin-12 - podjednotka p40 metabolismus MeSH
- kombinovaná farmakoterapie MeSH
- Leishmania tropica účinky léků patogenita MeSH
- leishmanióza kožní farmakoterapie MeSH
- levamisol aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy účinky léků MeSH
- meglumin antimoniát aplikace a dávkování farmakologie terapeutické užití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- myši MeSH
- senioři MeSH
- synthasa oxidu dusnatého, typ II metabolismus MeSH
- TNF-alfa metabolismus MeSH
- transformující růstový faktor beta metabolismus MeSH
- viabilita buněk účinky léků MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- myši MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiprotozoální látky MeSH
- fixní kombinace léků MeSH
- IL10 protein, human MeSH Prohlížeč
- interleukin-10 MeSH
- interleukin-12 - podjednotka p40 MeSH
- levamisol MeSH
- meglumin antimoniát MeSH
- NOS2 protein, human MeSH Prohlížeč
- synthasa oxidu dusnatého, typ II MeSH
- TNF-alfa MeSH
- transformující růstový faktor beta 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.
- Klíčová slova
- Cynara cardunculus, aldo-keto reductases, chronic diabetic complications, glucose toxicity, oxidative stress, polyol pathway,
- MeSH
- aldehydreduktasa antagonisté a inhibitory MeSH
- Cynara scolymus chemie MeSH
- glukosa farmakologie MeSH
- inhibitory enzymů farmakologie MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- listy rostlin chemie MeSH
- myši MeSH
- oční čočka účinky léků metabolismus MeSH
- orgánové kultury - kultivační techniky MeSH
- oxidační stres účinky léků MeSH
- reaktivní formy kyslíku farmakologie MeSH
- rostlinné extrakty farmakologie MeSH
- sorbitol metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Akr1b1 protein, rat MeSH Prohlížeč
- aldehydreduktasa MeSH
- glukosa MeSH
- inhibitory enzymů MeSH
- reaktivní formy kyslíku MeSH
- rostlinné extrakty MeSH
- sorbitol 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.
- Klíčová slova
- Cell cycle, Cell wall integrity, Cell wall signaling, Cellulose biosynthesis, Cytokinin, Nitrate reductase,
- MeSH
- Arabidopsis cytologie účinky léků genetika MeSH
- benzamidy farmakologie MeSH
- biologické modely MeSH
- buněčná stěna účinky léků metabolismus MeSH
- buněčný cyklus účinky léků genetika MeSH
- cytokininy farmakologie MeSH
- fenotyp MeSH
- homeostáza účinky léků MeSH
- kořeny rostlin cytologie účinky léků růst a vývoj MeSH
- messenger RNA genetika metabolismus MeSH
- nitrátreduktasa metabolismus MeSH
- osmóza MeSH
- proteiny huseníčku metabolismus MeSH
- regulace genové exprese u rostlin * účinky léků MeSH
- semenáček účinky léků genetika MeSH
- sorbitol farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- benzamidy MeSH
- cytokininy MeSH
- isoxaben MeSH Prohlížeč
- messenger RNA MeSH
- NIA1 protein, Arabidopsis MeSH Prohlížeč
- NIA2 protein, Arabidopsis MeSH Prohlížeč
- nitrátreduktasa MeSH
- proteiny huseníčku MeSH
- sorbitol 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.
- Klíčová slova
- Jenike shear tester, Sorbitol, flowability, force–displacement method, rebaudioside A, tablets,
- MeSH
- diterpeny kauranové chemie MeSH
- farmaceutická technologie metody MeSH
- pevnost v tahu MeSH
- pomocné látky chemie MeSH
- příprava léků metody MeSH
- sladidla chemie MeSH
- sorbitol chemie MeSH
- Stevia chemie MeSH
- tablety chemie MeSH
- tlak MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- diterpeny kauranové MeSH
- pomocné látky MeSH
- rebaudioside A MeSH Prohlížeč
- sladidla MeSH
- sorbitol MeSH
- tablety MeSH