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1.
BMC Womens Health ; 22(1): 519, 2022 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-36510239

RESUMO

BACKGROUND: Brain edema is a rare and serious complication of assisted reproductive technology (ART). The increased intracranial pressure and injured brain parenchyma are life-threatening and may even result in death. The pathogenesis may involve increased vascular permeability mediated by vascular endothelial growth factor and other vasoactive substances, including interleukin 6, interleukin 1ß, angiotensin II, insulin-like growth factor 1, transforming growth factor ß, and the renin-angiotensin system. CASE PRESENTATION: We presented a unique case report of a 29-year-old woman developed sudden irritability, blurred consciousness, and vomiting 8 h after oocyte retrieval. Blood examinations showed hyponatremia and cranial computed tomography showed swelling of the brain parenchyma. After therapeutic use of hypertonic saline and mannitol infusion, the patient's consciousness recovered and her neurological state improved. CONCLUSIONS: Brain edema is a rare and serious complication of ART. Quick infusion of hypertonic salt solution and mannitol is a key treatment. A good prognosis can be achieved after prompt treatment.


Assuntos
Edema Encefálico , Feminino , Humanos , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Edema Encefálico/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Solução Salina Hipertônica/uso terapêutico , Solução Salina Hipertônica/farmacologia , Manitol/uso terapêutico , Manitol/farmacologia
2.
Hear Res ; 426: 108646, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36403317

RESUMO

Cisplatin, a chemotherapeutic medication, remains in the cochlea indefinitely, causing permanent hearing loss. Mannitol, a diuretic medication, has been shown to increase the permeability of the blood labyrinth barrier (BLB). We hypothesize that mannitol increases the permeability of the BLB and therefore increases the rate of entry and egression of cisplatin and entry of otoprotective agents. Rats treated with cisplatin (t = 0) were given mannitol at either t = 0, t = 6 or t = 0,6 h. Another group of rats were treated with cisplatin with mannitol at 0 h and NAC/STS with and without mannitol at 6 h. Concurrent mannitol (t = 0) transiently increased cisplatin entry into the inner ear and exacerbated cisplatin-induced hearing loss. Delayed mannitol (t = 6) did not significantly increase cisplatin entry into the inner ear and preserved inner ear functionality and structure. Additional-delayed mannitol (t = 0,6) showed that the 2nd dose of mannitol prevented exacerbation of cisplatin with mannitol-induced hearing loss. A combination of delayed NAC/STS with mannitol (t = 6) was better than NAC/STS (t = 6) alone at providing partial to full protection against cisplatin with mannitol-induced hearing loss. In conclusion, mannitol injections at t = 6 h reduced cisplatin ototoxicity (instead of exacerbating cisplatin ototoxicity at t = 0 h), and it enhanced the otoprotective efficacy of antioxidants. This may provide an important therapeutic strategy to prevent cisplatin-induced hearing loss, a direct implication in protection against hearing loss in cisplatin chemotherapy.


Assuntos
Surdez , Orelha Interna , Perda Auditiva , Ototoxicidade , Animais , Ratos , Cisplatino/toxicidade , Manitol/farmacologia , Perda Auditiva/induzido quimicamente , Perda Auditiva/prevenção & controle
3.
Eur J Med Res ; 27(1): 254, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36404350

RESUMO

BACKGROUND: Traumatic brain injury (TBI) causes mortality and long-term disability among young adults and imposes a notable cost on the healthcare system. In addition to the first physical hit, secondary injury, which is associated with increased intracranial pressure (ICP), is defined as biochemical, cellular, and physiological changes after the physical injury. Mannitol and Hypertonic saline (HTS) are the treatment bases for elevated ICP in TBI. This systematic review and meta-analysis evaluates the effectiveness of HTS in the management of patients with TBI. METHODS: This study was conducted following the Joanna Briggs Institute (JBI) methods and PRISMA statement. A systematic search was performed through six databases in February 2022, to find studies that evaluated the effects of HTS, on increased ICP. Meta-analysis was performed using comprehensive meta-analysis (CMA). RESULTS: Out of 1321 results, 8 studies were included in the systematic review, and 3 of them were included in the quantitative synthesis. The results of the meta-analysis reached a 35.9% (95% CI 15.0-56.9) reduction in ICP in TBI patients receiving HTS, with no significant risk of publication bias (t-value = 0.38, df = 2, p-value = 0.73). The most common source of bias in our included studies was the transparency of blinding methods for both patients and outcome assessors. CONCLUSION: HTS can significantly reduce the ICP, which may prevent secondary injury. Also, based on the available evidence, HTS has relatively similar efficacy to Mannitol, which is considered the gold standard therapy for TBI, in boosting patients' neurological condition and reducing mortality rates.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Hipertensão Intracraniana , Humanos , Adulto Jovem , Pressão Intracraniana , Lesões Encefálicas/complicações , Solução Salina Hipertônica/uso terapêutico , Solução Salina Hipertônica/farmacologia , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/complicações , Manitol/uso terapêutico , Manitol/farmacologia
4.
Front Immunol ; 13: 1010526, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389821

RESUMO

Serum resistance is recognized as one of the most important pathogenic traits of bacterial pathogens, and no control measure is available. Based on our previous discovery that pathogenic Escherichia coli represses glycine, serine, and threonine metabolism to confer serum resistance and that the reactivation of this pathway by exogenous glycine could restore serum sensitivity, we further investigate the mechanism underlying the action of glycine in Vibrio alginolyticus. Thus, V. alginolyticus is treated with glycine, and the proteomic change is profiled with tandem mass tag-based quantitative proteomics. Compared to the control group, glycine treatment influences the expression of a total of 291 proteins. Among them, a trap-type mannitol/chloroaromatic compound transport system with periplasmic component, encoded by N646_0992, is the most significantly increased protein. In combination with the pathway enrichment analysis showing the altered fructose and mannitol metabolism, mannitol has emerged as a possible metabolite in enhancing the serum killing activity. To demonstrate this, exogenous mannitol reduces bacterial viability. This synergistic effect is further confirmed in a V. alginolyticus-Danio rerio infection model. Furthermore, the mechanism underlying mannitol-enabled serum killing is dependent on glycolysis and the pyruvate cycle that increases the deposition of complement components C3b and C5b-9 on the bacterial surface, whereas inhibiting glycolysis or the pyruvate cycle significantly weakened the synergistic effects and complement deposition. These data together suggest that mannitol is a potent metabolite in reversing the serum resistance of V. alginolyticus and has promising use in aquaculture.


Assuntos
Proteômica , Vibrio alginolyticus , Escherichia coli/metabolismo , Proteínas do Sistema Complemento/metabolismo , Glicina , Manitol/farmacologia , Piruvatos/metabolismo
5.
BMC Plant Biol ; 22(1): 447, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36114461

RESUMO

BACKGROUND: Plants are continuously exposed to changing environmental conditions and biotic attacks that affect plant growth. In crops, the inability to respond appropriately to stress has strong detrimental effects on agricultural production and yield. Ca2+ signalling plays a fundamental role in the response of plants to most abiotic and biotic stresses. However, research on stimulus-specific Ca2+ signals has mostly been pursued in Arabidopsis thaliana, while in other species these events are little investigated . RESULTS: In this study, we introduced the Ca2+ reporter-encoding gene APOAEQUORIN into the crop species barley (Hordeum vulgare). Measurements of the dynamic changes in [Ca2+]cyt in response to various stimuli such as NaCl, mannitol, H2O2, and flagellin 22 (flg22) revealed the occurrence of dose- as well as tissue-dependent [Ca2+]cyt transients. Moreover, the Ca2+ signatures were unique for each stimulus, suggesting the involvement of different Ca2+ signalling components in the corresponding stress response. Alongside, the barley Ca2+ signatures were compared to those produced by the phylogenetically distant model plant Arabidopsis. Notable differences in temporal kinetics and dose responses were observed, implying species-specific differences in stress response mechanisms. The plasma membrane Ca2+ channel blocker La3+ strongly inhibited the [Ca2+]cyt response to all tested stimuli, indicating a critical role of extracellular Ca2+ in the induction of stress-associated Ca2+ signatures in barley. Moreover, by analysing spatio-temporal dynamics of the [Ca2+]cyt transients along the developmental gradient of the barley leaf blade we demonstrate that different parts of the barley leaf show quantitative differences in [Ca2+]cyt transients in response to NaCl and H2O2. There were only marginal differences in the response to flg22, indicative of developmental stage-dependent Ca2+ responses specifically to NaCl and H2O2. CONCLUSION: This study reveals tissue-specific Ca2+ signals with stimulus-specific kinetics in the crop species barley, as well as quantitative differences along the barley leaf blade. A number of notable differences to the model plants Arabidopsis may be linked to different stimulus sensitivity. These transgenic barley reporter lines thus present a valuable tool to further analyse mechanisms of Ca2+ signalling in this crop and to gain insights into the variation of Ca2+-dependent stress responses between stress-susceptible and -resistant species.


Assuntos
Arabidopsis , Hordeum , Arabidopsis/genética , Cálcio/metabolismo , Flagelina/metabolismo , Flagelina/farmacologia , Hordeum/metabolismo , Peróxido de Hidrogênio/metabolismo , Manitol/metabolismo , Manitol/farmacologia , Plantas/metabolismo , Cloreto de Sódio/farmacologia
6.
J Plant Physiol ; 278: 153810, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36162212

RESUMO

Abscisic acid (ABA) plays primary regulatory roles in abiotic stress tolerance and seed germination. Here, we report a unique novel Arabidopsis abscisic acid-insensitive mutant, abr (abscisic acid resistance), which was able to germinate in medium containing high ABA concentrations and tolerant to abiotic stress tolerance. We observed that abr mutant accumulated more anthocyanins by ABA treatment than did the wild type (WT). Dimethylthiourea (DMTU, an H2O2 scavenger) was effective in inhibiting ABA-induced anthocyanins accumulation. RNA-seq showed that the expression of anthocyanins synthesis, antioxidant enzyme and stress-related genes were specifically increased in ABA-treated abr seedlings, suggesting that the abr mutation affects stress response as well as ABA responses. Interestingly, seedlings accumulating anthocyanins exhibited more tolerance to mannitol and NaCl compared to wild type. We propose that ABA-induced H2O2 generation triggers the foliar anthocyanins accumulation, which, in turn, enhances the abiotic stress tolerance in abr mutant.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Antocianinas/metabolismo , Antioxidantes/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Germinação , Peróxido de Hidrogênio/metabolismo , Manitol/farmacologia , Mutação/genética , Plântula/metabolismo , Cloreto de Sódio/farmacologia , Estresse Fisiológico/genética
7.
Injury ; 53(11): 3729-3735, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36114014

RESUMO

BACKGROUND: Until now, it has remained difficult for doctors to make an informative decision as to which concentration of hypertonic saline (HTS) is more beneficial for patients with traumatic brain injury (TBI). We therefore investigate the effect of different concentrations of hypertonic saline on mortality and ICP lowering efficacy in this group of patients. METHODS: Several databases including Ovid MEDLINE, Ovid EMBASE, PubMed, and Cochrane Central Register of Controlled Trials were searched comprehensively from inception to February 28, 2022. We only included RCTs that compared HTS with different concentrations and mannitol in adult patients with TBI. The main outcome was mortality from any cause. We reported relative risks (RR) and 95% confidence intervals (CIs) from direct meta-analysis and 95% credible intervals (CrIs) from network meta-analysis. RESULTS: Overall, 13 trials containing 593 patients were included in this study. Direct analysis revealed that HTS was associated with decreased risk of all-cause mortality (RR, 1.29; 95% CI: 1.08 to 1.54). In the network meta-analysis, 5% HTS was associated with a significant decrease in all-cause mortality compared with mannitol (RR 0.34, 95% CrI: 0.14 to 0.72). We also found 7.5% HTS was associated with a significant increase in all-cause mortality compared with 5% HTS (RR, 2.87; 95% CrI: 1.00 to 8.99). CONCLUSIONS: Among patients with TBI, the application of 5% HTS was associated with decreased all-cause mortality compared with mannitol and other concentration. Treatments with 10% and 15% HTS was more likely to decrease ICP compared with other fluids. More trials are needed to verify the current findings.


Assuntos
Lesões Encefálicas Traumáticas , Hipertensão Intracraniana , Humanos , Adulto , Pressão Intracraniana , Solução Salina Hipertônica/uso terapêutico , Solução Salina Hipertônica/farmacologia , Lesões Encefálicas Traumáticas/complicações , Manitol/uso terapêutico , Manitol/farmacologia
8.
Vox Sang ; 117(10): 1163-1170, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36102116

RESUMO

BACKGROUND AND OBJECTIVES: Di-ethyl-hexyl-phthalate (DEHP) is currently the main plasticizer used for whole blood collection systems. However, in Europe, after May 2025, DEHP may no longer be used above 0.1% (w/w) in medical devices. DEHP stabilizes red cell membranes, thereby suppressing haemolysis during storage. Here we compared in vitro quality parameters of red cell concentrates (RCCs) collected and stored in DEHP-, DINCH- or DINCH/BTHC-PVC hybrid blood bags with saline-adenine-glucose-mannitol (SAGM) or phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM) storage solution. Last, we performed haemovigilance surveillance for RCC collected in DINCH-PVC and stored in PAGGSM/BTHC-PVC. MATERIALS AND METHODS: In vitro quality parameters of RCC were determined during 42 days of storage. Haemovigilance surveillance was conducted to compare the frequency and type of transfusion reaction. RESULTS: Haemolysis levels were increased in SAGM/BTHC-PVC as compared to SAGM/DEHP-PVC (0.66% ± 0.18% vs. 0.36% ± 0.17%). PAGGSM storage solution was able to adequately suppress haemolysis to levels observed during storage in SAGM/DEHP-PVC, both in BTHC-PVC (0.38% ± 0.12%), and to a slightly lesser extent in DINCH-PVC (0.48% ± 0.17%). A total of 1650 PAGGSM/BTHC-PVC and 5662 SAGM/DEHP-PVC RCC were transfused yielding a transfusion reaction frequency of 0.24% (95% CI 0.0000-0.0048) and 0.44% (95% CI 0.0027-0.0061) respectively. CONCLUSION: The in vitro quality of RCC stored in PAGGSM/BTHC-PVC and SAGM/DEHP-PVC is comparable. There is no indication that transfusion of erythrocytes stored in PAGGSM/BTHC-PVC results in increased transfusion reaction frequency. These initial results provide a basis for further clinical evaluation to narrow down the confidence interval of transfusion reaction frequency.


Assuntos
Carcinoma de Células Renais , Dietilexilftalato , Neoplasias Renais , Reação Transfusional , Adenina/farmacologia , Preservação de Sangue/métodos , Butiratos , Carcinoma de Células Renais/metabolismo , Eritrócitos/metabolismo , Glucose/metabolismo , Guanosina , Hemólise , Humanos , Neoplasias Renais/metabolismo , Manitol/farmacologia , Fosfatos/metabolismo , Plastificantes , Cloreto de Polivinila , Cloreto de Sódio
9.
Int J Mol Sci ; 23(17)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36077569

RESUMO

The present study induced prolonged hyperglycemia (a hallmark symptom of Type 2 diabetes [T2DM]) in Danio rerio (zebrafish) for eight or twelve weeks. The goal of this research was to study cognitive decline as well as vision loss in hyperglycemic zebrafish. Fish were submerged in glucose for eight or twelve weeks, after which they were assessed with both a cognitive assay (three-chamber choice) and a visual assay (optomotor response (OMR)). Zebrafish were also studied during recovery from hyperglycemia. Here, fish were removed from the hyperglycemic environment for 4 weeks after either 4 or 8 weeks in glucose, and cognition and vision was again assessed. The 8- and 12-week cognitive results revealed that water-treated fish showed evidence of learning while glucose- and mannitol-treated fish did not within the three-day testing period. OMR results identified an osmotic effect with glucose-treated fish having significantly fewer positive rotations than water-treated fish but comparable rotations to mannitol-treated fish. The 8- and 12-week recovery results showed that 4 weeks was not enough time to fully recovery from the hyperglycemic insult sustained.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Hiperglicemia , Animais , Cognição , Disfunção Cognitiva/etiologia , Glucose , Hiperglicemia/complicações , Manitol/farmacologia , Água , Peixe-Zebra/fisiologia
10.
Physiol Plant ; 174(5): e13786, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36169530

RESUMO

Plants in nature commonly encounter combined stress scenarios. The response to combined stressors is often unpredictable from the response to single stresses. To address stress interference in roots, we applied salinity, heat, and high light to hydroponically grown sugar beet. Two main patterns of metabolomic acclimation were apparent. High salt of 300 mM NaCl considerably lowered metabolite amounts, for example, those of most amino acids, γ-amino butyric acid (GABA), and glucose. Very few metabolites revealed the opposite trend with increased contents at high salts, mostly organic acids such as citric acid and isocitric acid, but also tryptophan, tyrosine, and the compatible solute proline. High temperature (31°C vs. 21°C) also frequently lowered root metabolite pools. The individual effects of salinity and heat were superimposed under combined stress. Under high light and high salt conditions, there was a significant decline in root chloride, mannitol, ribulose 5-P, cysteine, and l-aspartate contents. The results reveal the complex interaction pattern of environmental parameters and urge researchers to elaborate in much more detail and width on combinatorial stress effects to bridge work under controlled growth conditions to growth in nature, and also to better understand acclimation to the consequences of climate change.


Assuntos
Beta vulgaris , Beta vulgaris/metabolismo , Cloreto de Sódio/farmacologia , Regulação da Expressão Gênica de Plantas , Temperatura Alta , Cloretos/metabolismo , Cisteína/metabolismo , Triptofano , Ácido Aspártico , Sais/metabolismo , Sais/farmacologia , Salinidade , Prolina/metabolismo , Redes e Vias Metabólicas , Ácido gama-Aminobutírico/farmacologia , Manitol/farmacologia , Ácido Cítrico/metabolismo , Glucose/metabolismo , Tirosina/metabolismo , Tirosina/farmacologia , Açúcares/metabolismo , Raízes de Plantas/metabolismo , Estresse Fisiológico
11.
PLoS One ; 17(8): e0273208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36006975

RESUMO

The sympathetic nervous system is highly involved in the regulation of gastrointestinal functions such as luminal alkalinisation and fluid absorption. However, the exact mechanisms are not clear. This study aimed to delineate how α2-adrenergic receptor stimulation reduces duodenal luminal alkalinisation and induces net fluid absorption. This was tested by perfusing the duodenum of anesthetized rats with isotonic solutions devoid of Cl- and/or Na+, in the absence and presence of the α2-adrenoceptor agonist clonidine. The clonidine was also studied in rats treated with dimethylamiloride (a Na+/H+ exchange inhibitor), vasoactive intestinal peptide, and the nicotinic receptor antagonist hexamethonium. Clonidine reduced luminal alkalinisation and induced net fluid absorption. The Cl--free solution decreased luminal alkalinisation and abolished net fluid absorption, but did not prevent clonidine from doing so. Both the Na+-free solution and luminal dimethylamiloride increased luminal alkalinisation and abolished net fluid absorption, effects counteracted by clonidine. The NaCl-free solution (D-mannitol) did not affect luminal alkalinisation, but reduced net fluid absorption. Clonidine reduced luminal alkalinisation and induced net fluid absorption in rats perfused luminally with mannitol. However, clonidine did not affect the vasoactive intestinal peptide-induced increase in luminal alkalinisation or fluid secretion. Pre-treatment with hexamethonium abolished the effects of clonidine on luminal alkalinisation and net fluid flux. In summary, our in vivo experiments showed that clonidine-induced reduction in luminal alkalinisation and induction of net fluid absorption was unrelated to luminal Na+ and Cl-, or to apical Na+/H+ or Cl-/HCO3- exchangers. Instead, clonidine seems to exert its effects via suppression of nicotinic receptor-activated acetylcholine secretomotor neurons.


Assuntos
Bicarbonatos , Receptores Nicotínicos , Animais , Bicarbonatos/metabolismo , Clonidina/farmacologia , Duodeno/metabolismo , Hexametônio/farmacologia , Manitol/farmacologia , Ratos , Receptores Adrenérgicos , Sódio/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia
12.
Gene ; 844: 146828, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-35998844

RESUMO

Sorafenib is an FDA approved chemotherapeutic against hepatocellular carcinoma (HCC) yet associated with various resistance mechanisms. The role of high glucose status on sorafenib action is still to be elucidated. This study clarifies such interaction, taking HepG2 cell lines as HCC models, MALAT1 and H19 as molecular players. HepG2 cell lines were purchased and classified into 8 groups. High glucose status was set by using d-glucose (33 mM) with insulin (1 µM). Mannitol (27.5 mM) was used as a negative osmotic control. Sorafenib was prepared at 15 µM and 20 µM. Cellular viability was assessed with MTT viability assay. Then, with trypan blue viability assay, the results were double checked and HepG2 morphology was examined by optical microscopy. MALAT1 and H19 RQs were assessed by real time PCR (RT-PCR). Results show that in comparison with sorafenib impact on HepG2, high glucose status drops cellular viability to 83.13 % (p < 0.01). With hyperosmolar mannitol, it decreases cellular viability to 72.89 % (p < 0.001). Regarding the molecular impact, hyperosmolar mannitol with sorafenib elevates both MALAT1 and H19 RQs. Yet, high glucose status elevates MALAT1and declines H19 (p < 0.05 and p < 0.001 for MALAT1 and H19 comparisons respectively). Therefore, the impact of high glucose status could be, in part, attributed to the hyperosmolar stress it induces on HepG2. Also, hyperosmolar mannitol, owing to its cytotoxic impact, is recommended for further confirmatory studies either as a separate therapeutic or as an adjuvant to sorafenib.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Glucose/farmacologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Manitol/farmacologia , Manitol/uso terapêutico , Sorafenibe/farmacologia
13.
PLoS One ; 17(8): e0273921, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36044512

RESUMO

Transplantation is lifesaving and the most effective treatment for end-stage organ failure. The transplantation success depends on the functional preservation of organs prior to transplantation. Currently, the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most commonly used preservation solutions. Despite intensive efforts, the functional preservation of solid organs prior to transplantation is limited to hours. In this study, we modified the UW solution containing components from both the UW and HTK solutions and analyzed their tissue-protective effect against ischemic injury. The composition of the UW solution was changed by reducing hydroxyethyl starch concentration and adding Histidine/Histidine-HCl which is the main component of HTK solution. Additionally, the preservation solutions were supplemented with melatonin and glucosamine. The protective effects of the preservation solutions were assessed by biochemical and microscopical analysis at 2, 10, 24, and 72 h after preserving the rat kidneys with static cold storage. Lactate dehydrogenase (LDH) activity in preservation solutions was measured at 2, 10, 24, and 72. It was not detectable at 2 h of preservation in all groups and 10 h of preservation in modified UW+melatonin (mUW-m) and modified UW+glucosamine (mUW-g) groups. At the 72nd hour, the lowest LDH activity (0.91 IU/g (0.63-1.17)) was measured in the mUW-m group. In comparison to the UW group, histopathological damage score was low in modified UW (mUW), mUW-m, and mUW-g groups at 10, 24, and 72 hours. The mUW-m solution at low temperature was an effective and suitable solution to protect renal tissue for up to 72 h.


Assuntos
Isquemia , Rim , Melatonina , Soluções para Preservação de Órgãos , Adenosina , Alopurinol/farmacologia , Animais , Glucosamina , Glucose/farmacologia , Glutationa/farmacologia , Histidina/farmacologia , Insulina/farmacologia , Isquemia/tratamento farmacológico , Isquemia/metabolismo , Rim/patologia , Manitol/farmacologia , Melatonina/farmacologia , Preservação de Órgãos/métodos , Soluções para Preservação de Órgãos/química , Soluções para Preservação de Órgãos/farmacologia , Cloreto de Potássio/farmacologia , Rafinose/farmacologia , Ratos
14.
Cells ; 11(11)2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35681457

RESUMO

Hyperosmolality can occur during industrial fed-batch cultivation processes of Chinese hamster ovary (CHO) cells as highly concentrated feed and base solutions are added to replenish nutrients and regulate pH values. Some effects of hyperosmolality, such as increased cell size and growth inhibition, have been elucidated by previous research, but the impact of hyperosmolality and the specific effects of the added osmotic-active reagents have rarely been disentangled. In this study, CHO cells were exposed to four osmotic conditions between 300 mOsm/kg (physiologic condition) and 530 mOsm/kg (extreme hyperosmolality) caused by the addition of either high-glucose-supplemented industrial feed or mannitol as an osmotic control. We present novel single-cell cultivation data revealing heterogeneity in mass gain and cell division in response to these treatments. Exposure to extreme mannitol-induced hyperosmolality and to high-glucose-oversupplemented feed causes cell cycle termination, mtDNA damage, and mitochondrial membrane depolarization, which hints at the onset of premature stress-induced senescence. Thus, this study shows that both mannitol-induced hyperosmolality (530 mOsm/kg) and glucose overfeeding induce severe negative effects on cell growth and mitochondrial activity; therefore, they need to be considered during process development for commercial production.


Assuntos
Glucose , Análise de Célula Única , Animais , Células CHO , Cricetinae , Cricetulus , Glucose/metabolismo , Manitol/farmacologia
15.
Plant Sci ; 322: 111350, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35709980

RESUMO

Seed germination is the first step of seedling establishment, which is particularly sensitive to drought stress. Elucidating the mechanism regulating seed germination under drought stress is of great importance. We showed that overexpressing Tomato Ethylene Responsive Factor 1 (TERF1), an ERF transcription factor in the ethylene signaling pathway, significantly reduced seed sensitivity to mannitol treatment during seed germination. Germination assay demonstrated that TERF1 could activate gibberellin acid (GA) signaling pathway independent on GA metabolism during germination. By comparative transcriptome analysis (mannitol vs normal germination condition, mannitol vs mannitol plus paclobutrazol (PAC, an inhibitor of GA biosynthesis)) we identified the genes regulated by TERF1 specifically under mannitol treatment and confirmed that TERF1 could activate GA signaling pathway independent on GA metabolism, which were consistent with the germination assay with mannitol and mannitol plus PAC treatment. Based on sugar, gene expression and germination analysis we proved that TERF1 promoted seed germination through glucose signaling pathway mediated by GA. Thus our study provides an underlying mechanism for activating GA signaling pathway by TERF1 during seed germination under osmotic conditions.


Assuntos
Giberelinas , Ácido Abscísico/metabolismo , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Germinação/genética , Giberelinas/metabolismo , Manitol/metabolismo , Manitol/farmacologia , Sementes/genética , Sementes/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
Urologiia ; (2): 18-26, 2022 May.
Artigo em Russo | MEDLINE | ID: mdl-35485810

RESUMO

While performing surgical treatment of the localized form of renal cell cancer by means of open or laparoscopic partial nephrectomy, renal warm ischemia is an important issue. Using renal warm ischemia allows to prevent parenchymal bleeding, to optimize conditions for resection of the tumor and to increase significantly the efficiency of hemostasis. However, an important problem is the probability of ischemic hypoxic damage of the remaining part of the kidney tissue during renal warm ischemia and renal functional impairment in the postoperative period. AIM: To compare nephroprotective activity of sodium fumarate, mannitol and furosemide using experimental model of 30- and 60-minute renal warm ischemia in rabbits. MATERIALS AND METHODS: The experiments were carried out on 360 conventional male-rabbits of the "Chinchilla" breed weighed 2,6+/-0,3 kg which were allocated into 10 groups. The control group No1 included intact animals, the control group No2 included the rabbits in which renal artery was not clamped. For the animals from the trial groups (No3-No10) the experimental model of 30- and 60-minute renal warm ischemia was used. In groups No3 and No4 no drugs were provided. Other rabbits undergone renal warm ischemia with a protection by sodium fumarate (groups No5 and No6 - 1,5 ml/kg IV), lasix (groups No7 and No8 - 3,0 mg/kg IV) and mannitol (No9 and No10 - 1,0 g/kg IV). The influence of renal warm ischemia on the renal tissue ultrastructure and the levels of NGAL, Cystatin-C and creatinine in blood and urine were studied. RESULTS: During experimental pharmacologically uncorrected 30-minute renal warm ischemia in animals, edema of the terminal part of microvilli of the proximal tubules epithelium, an increase of lysosome number in the hyaloplasm of epithelial cells, appearance of flaky content of medium electronic density in the lumens of distal tubules and collecting tubules, as well as sharp peak-like increase of NGAL and cystatin-C in blood and urine were observed. Increasing the time of ischemia up to 60 minutes was accompanied by more severe disturbances. In groups where sodium fumarate, lasix and mannitol were used the observed ultrastructural disturbances were expressed to lesser extent, whereas sodium fumarate demonstrated the best nephroprotective activity. After using mannitol the severity of disturbances was less than in the groups where mannitol, lasix or sodium fumarate were not given. Lasix and sodium salt of fumaric acid showed a higher nephroprotective activity. The best results were received in the animals received sodium fumarate. CONCLUSIONS: The studied drugs provided a nephroprotective effect regarding ischemia of rabbit kidney. The effect of sodium fumarate was the most pronounced, followed by furosemide and, to a lesser extent, mannitol. Use of sodium fumarate allows to protect and stimulate the kidney tissue effectively during oxygen deprivation under ischemic state.


Assuntos
Neoplasias Renais , Isquemia Quente , Animais , Feminino , Fumaratos , Furosemida/farmacologia , Humanos , Isquemia , Rim/cirurgia , Neoplasias Renais/cirurgia , Lipocalina-2 , Masculino , Manitol/farmacologia , Coelhos , Isquemia Quente/métodos
18.
Molecules ; 27(8)2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35458647

RESUMO

Media supplementation with exogenous chemicals is known to stimulate the accumulation of important lipids produced by microalgae and thraustochytrids. However, the roles of exogenous chemicals in promoting and preserving the terpenoids pool of thraustochytrids have been rarely investigated. Here, we realized the effects of two media supplements-mannitol and biotin-on the biomass and squalene production by a thraustochytrid strain (Thraustochytrium sp. ATCC 26185) and elucidated their mechanism of action. A significant change in the biomass was not evident with the exogenous addition of these supplements. However, with mannitol (1 g/L) supplementation, the ATCC 26185 culture achieved the best concentration (642 ± 13.6 mg/L) and yield (72.9 ± 9.6 mg/g) of squalene, which were 1.5-fold that of the control culture (non-supplemented). Similarly, with biotin supplementation (0.15 mg/L), the culture showed 459 ± 2.9 g/L and 55.7 ± 3.2 mg/g of squalene concentration and yield, respectively. The glucose uptake rate at 24 h of fermentation increased markedly with mannitol (0.31 g/Lh-1) or biotin (0.26 g/Lh-1) supplemented culture compared with non-supplemented culture (0.09 g/Lh-1). In addition, the reactive oxygen species (ROS) level of culture supplemented with mannitol remained alleviated during the entire period of fermentation while it alleviated after 24 h with biotin supplementation. The ∆ROS with mannitol was better compared with biotin supplementation. The total antioxidant capacity (T-AOC) of the supplemented culture was more than 50% during the late stage (72-96 h) of fermentation. Our study provides the potential of mannitol and biotin to enhance squalene yield and the first lines of experimental evidence for their protective role against oxidative stress during the culture of thraustochytrids.


Assuntos
Esqualeno , Estramenópilas , Antioxidantes/farmacologia , Biotina , Meios de Cultura/farmacologia , Suplementos Nutricionais , Fermentação , Glucose , Manitol/farmacologia , Esqualeno/farmacologia
19.
Blood Adv ; 6(13): 3899-3910, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35477178

RESUMO

Additive solutions are used to limit changes that red blood cells (RBCs) undergo during storage. Several studies have shown better preservation of glucose and redox metabolism using the alkaline additive solution PAGGGM (phosphate-adenine-glucose-guanosine-gluconate-mannitol). In this randomized open-label intervention trial in 20 healthy volunteers, the effect of storage, PAGGGM vs SAGM (saline-adenine-glucose-mannitol), on posttransfusion recovery (PTR) and metabolic restoration after transfusion was assessed. Subjects received an autologous biotinylated RBC concentrate stored for 35 days in SAGM or PAGGGM. As a reference for the PTR, a 2-day stored autologous biotinylated RBC concentrate stored in SAGM was simultaneously transfused. RBC phenotype and PTR were assessed after transfusion. Biotinylated RBCs were isolated from the circulation for metabolomics analysis up to 24 hours after transfusion. The PTR was significantly higher in the 2-day stored RBCs than in 35-day stored RBCs 2 and 7 days after transfusion: 96% (90 to 99) vs 72% (66 to 89) and 96% (90 to 99) vs 72% (66 to 89), respectively. PTR of SAGM- and PAGGGM-stored RBCs did not differ significantly. Glucose and redox metabolism were better preserved in PAGGGM-stored RBCs. The differences measured in the blood bag remained present only until 1 day after transfusion. No differences in RBC phenotype were found besides an increased complement C3 deposition on 35-day RBCs stored in PAGGGM. Our data indicate that despite better metabolic preservation, PAGGGM is not a suitable alternative for SAGM because storage in PAGGGM did not result in an increased PTR. Finally, RBCs recovered from circulation after transfusion showed reversal of the metabolic storage lesion in vivo within a day. This study is registered in the Dutch trial register (NTR6492).


Assuntos
Adenina , Preservação de Sangue , Eritrócitos/metabolismo , Glucose/metabolismo , Glucose/farmacologia , Humanos , Manitol/metabolismo , Manitol/farmacologia
20.
J Cardiovasc Pharmacol ; 79(6): 896-903, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35249963

RESUMO

ABSTRACT: Shock and subsequent resuscitation provoke ischemia-reperfusion injury. Trimetazidine (TMZ), allopurinol (ALO), and histidine-tryptophan-ketoglutarate (HTK) solution, can protect from ischemia-reperfusion injury in chronic coronary syndromes and in transplantation. The objective of the current study is to compare, in a hemorrhagic shock and standard resuscitation animal model, organ damage parameters between placebo and treatment with TMZ, ALO, or HTK. Shock was induced in Wistar rats by controlled arterial bleeding, maintaining mean arterial pressure between 38 and 42 mm Hg for 60 minutes; then, drawn blood was reinfused. Animals were divided into: Sham (n = 4), Control (n = 6), TMZ (n = 7), ALO (n = 9), and HTK (n = 7). At the end of the experiment, animals were sacrificed and tissue harvested. TMZ, ALO and HTK decreased histopathologic damage in heart [Control: 1.72 (1.7-1.77); TMZ: 1.75 (1.72-1.79); ALO: 1.75 (1.74-1.8); HTK: 1.82 (1.78-1.85); all P < 0.05], kidney [Control: 3 (2-3); TMZ: 1 (1-2); ALO: 1 (1-1); HTK: 1(1-1); all P < 0.05] and intestine [Control: 3 (2-3); TMZ: 1 (1-2); ALO: 1 (1-1); HTK: 1 (0-2); all P < 0.05]. Also, treatment with TMZ, ALO, and HTK increased immunohistochemical expression of thioredoxin-1 in heart [Control: 6.6 (5.6-7.4); TMZ: 9.5 (8.1-9.7); ALO: 9.1 (8.4-10.2); HTK: 14.2 (12.6-15); all P < 0.05]; and kidney [Control: 4.6 (4-5.1); TMZ: 9.7 (9.3-9.9); ALO: 9.6 (9-9.9); HTK: 16.7 (16.1-17); all P < 0.05]. In an experimental model of hemorrhagic shock, TMZ, ALO, and HTK solution attenuated cell damage in multiple parenchyma and increased antioxidant defenses.


Assuntos
Fármacos Cardiovasculares , Soluções para Preservação de Órgãos , Traumatismo por Reperfusão , Choque Hemorrágico , Alopurinol , Animais , Modelos Animais de Doenças , Glucose , Glutationa , Insulina , Manitol/farmacologia , Soluções para Preservação de Órgãos/farmacologia , Cloreto de Potássio/farmacologia , Procaína , Ratos , Ratos Wistar , Choque Hemorrágico/tratamento farmacológico
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