ABSTRACT
BACKGROUND: The role of carbohydrate antigen 19-9 (CA 19-9) in response assessment among patients with intrahepatic cholangiocarcinoma (iCCA) remains unknown. The authors studied the association of the CA 19-9 response (defined as a reduction >50% from baseline) with the radiologic response and the outcome in patients with unresectable iCCA. METHODS: A prospective cohort of 422 patients who were initially diagnosed with unresectable iCCA, had baseline CA 19-9 levels ≥100 U/mL, and received treatment with systemic therapies at the authors' institution between January 2017 and December 2021 were enrolled in this study. The radiologic response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A landmark assessment of the CA 19-9 response and the radiologic response was performed. The associations between CA 19-9 response and imaging response, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Two hundred sixty-seven patients (63.3%) had a CA 19-9 response. A CA 19-9 response was observed in 123 of 132 (93.2%) radiologic responders and in 144 of 290 (49.7%) radiologic nonresponders (p < .001). CA 19-9 responders outperformed nonresponders in median PFS (10.6 vs. 3.6 months; hazard ratio [HR], 4.8 months; 95% confidence interval [CI], 3.8-6.0 months; p < .001) and OS (21.4 vs. 6.3 months; HR, 5.3 months; 95% CI, 4.2-6.7 months; p < .001). The common independent predictors of both OS and PFS included metastasis, CA 19-9 nonresponder status, and radiologic nonresponder status in multivariable analysis. CONCLUSIONS: CA 19-9 response is a valuable addition to assess tumor response and is associated with improved outcomes in patients with iCCA. Achieving a CA 19-9 response should be one of the therapeutic objectives of patients with iCCA after systemic therapies. PLAIN LANGUAGE SUMMARY: A decline in carbohydrate antigen 19-9 levels from elevated baseline levels should be one of the therapeutic aims of patients with intrahepatic cholangiocarcinoma who are managed with systemic therapies.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Humans , Prospective Studies , Cholangiocarcinoma/drug therapy , Bile Ducts, Intrahepatic/diagnostic imaging , Bile Ducts, Intrahepatic/pathology , Carbohydrates/therapeutic use , Retrospective StudiesABSTRACT
BACKGROUND: Mucin disulfide cross-links mediate pathologic mucus formation in muco-obstructive lung diseases. MUC-031, a novel thiol-modified carbohydrate compound, cleaves disulfides to cause mucolysis. The aim of this study was to determine the mucolytic and therapeutic effects of MUC-031 in sputum from patients with cystic fibrosis (CF) and mice with muco-obstructive lung disease (ßENaC-Tg mice). METHODS: We compared the mucolytic efficacy of MUC-031 and existing mucolytics (N-acetylcysteine (NAC) and recombinant human deoxyribonuclease I (rhDNase)) using rheology to measure the elastic modulus (G') of CF sputum, and we tested effects of MUC-031 on airway mucus plugging, inflammation and survival in ßENaC-Tg mice to determine its mucolytic efficacy in vivo. RESULTS: In CF sputum, compared to the effects of rhDNase and NAC, MUC-031 caused a larger decrease in sputum G', was faster in decreasing sputum G' by 50% and caused mucolysis of a larger proportion of sputum samples within 15â min of drug addition. Compared to vehicle control, three treatments with MUC-031 in 1â day in adult ßENaC-Tg mice decreased airway mucus content (16.8±3.2 versus 7.5±1.2â nL·mm-2, p<0.01) and bronchoalveolar lavage cells (73 833±6930 versus 47 679±7736 cells·mL-1, p<0.05). Twice-daily treatment with MUC-031 for 2â weeks also caused decreases in these outcomes in adult and neonatal ßENaC-Tg mice and reduced mortality from 37% in vehicle-treated ßENaC-Tg neonates to 21% in those treated with MUC-031 (p<0.05). CONCLUSION: MUC-031 is a potent and fast-acting mucolytic that decreases airway mucus plugging, lessens airway inflammation and improves survival in ßENaC-Tg mice. These data provide rationale for human trials of MUC-031 in muco-obstructive lung diseases.
Subject(s)
Cystic Fibrosis , Lung Diseases, Obstructive , Adult , Humans , Mice , Animals , Expectorants/therapeutic use , Sulfhydryl Compounds/pharmacology , Sulfhydryl Compounds/therapeutic use , Acetylcysteine/pharmacology , Acetylcysteine/therapeutic use , Sputum , Lung Diseases, Obstructive/drug therapy , Inflammation/pathology , Carbohydrates/pharmacology , Carbohydrates/therapeutic use , LungABSTRACT
BACKGROUND: Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers. METHODS: In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test. RESULTS: Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501). CONCLUSION: Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Humans , Neoadjuvant Therapy/adverse effects , CA-19-9 Antigen/therapeutic use , Randomized Controlled Trials as Topic , Pancreatic Neoplasms/surgery , Adenocarcinoma/pathology , Carbohydrates/therapeutic use , Retrospective Studies , Chemoradiotherapy , Pancreatic NeoplasmsABSTRACT
The ketogenic diet (KD) is a widely used therapeutic option for individuals with medically refractory epilepsy. As the diet's name implies, ketosis is a historically important component of the diet, but it is not well understood how important ketosis is for seizure control. The ketogenic ratio is defined as the ratio of fat to carbohydrate plus protein by weight in the diet (grams). Traditionally, the classic KD contains a 4:1 ratio, and a very high proportion of fat in the diet. The classic KD, with its high proportion of fat and limited carbohydrate intake can be restrictive for patients with epilepsy. Recently, there is experience with use of lower ketogenic ratios and less-restrictive diets such as the modified Atkins diet and the low glycemic index treatment. In this narrative review, we examine the role of ketosis and ketogenic ratios in determining the efficacy of the KD in children with epilepsy.
Subject(s)
Diet, Ketogenic , Drug Resistant Epilepsy , Epilepsy , Ketosis , Child , Humans , Epilepsy/drug therapy , Ketone Bodies/therapeutic use , Carbohydrates/therapeutic use , Treatment Outcome , Diet, Carbohydrate-RestrictedABSTRACT
BACKGROUND: Several randomized clinical trials were done to determine whether supplementation with a high caloric diet, either through carbohydrate or lipid supplementation, is safe, tolerable and improves survival. However, most of these trials are small and the results are conflicting. METHODS: Randomized prospective trials utilizing high caloric supplementation among patients with amyotrophic lateral sclerosis (ALS) were searched using the terms [("amyotrophic lateral sclerosis" or "motor neuron disease" or "ALS" or "MND") and ("high calorie" or "high fat" or "high protein" or "high carbohydrate" or "supplementation")] in Medline, Cochrane, Embase, Scopus, Prospero and Herdin by two independent neurologists. Journal articles deemed relevant were assessed for eligibility. MAIN RESULTS: There were 57 articles obtained from databases, 49 of which were excluded. Four articles were further excluded since all of them had different interventions. Overall, there were 311 ALS patients included in the study, 176 of them were from the intervention group while 135 were used as controls. Overall, high caloric supplementation in ALS was deemed safe and tolerable, and also when adverse events, tolerability and mortality are combined using meta-analysis. Although in most publications the efficacy of giving high caloric supplementation has been generally beneficial, some of the outcome parameters are not statistically different from controls when studies are combined using meta-analysis. CONCLUSIONS: Current evidence suggests that high calorie supplementation is generally safe and tolerable for patients with ALS. However, it has not been shown to be efficacious in improving weight and functional disability.
Subject(s)
Amyotrophic Lateral Sclerosis , Motor Neuron Disease , Humans , Amyotrophic Lateral Sclerosis/therapy , Prospective Studies , Diet , Carbohydrates/therapeutic useABSTRACT
AIM: To investigate the effect of ursodeoxycholic acid (UDCA) on the degree of steatosis, indicators of carbohydrate, lipid metabolism, body weight in patients with type 2 diabetes mellitus (DM) in combination with non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: A prospective cohort comparative study included 36 patients with DM and NAFLD. Patients received UDCA at a dose of 15 mg/kg/day for 6 months, and also followed the recommendations for lifestyle changes through diet and exercise. To compare the results obtained during the study, a control group of patients was recruited that met the criteria for inclusion in the study. The statistical analysis included an assessment of the normality of the distribution of quantitative indicators, followed by the determination of the mean values and standard deviation or medians and quartiles, depending on the nature of the distribution, the reliability coefficient was determined by the Student, by Wilcoxon. Statistical processing was carried out in the Statistica 10 program. RESULTS: According to the results of the study, a positive trend was noted in the change in the severity of fatty hepatosis. During the study, a statistically significant decrease in the level of ALT, AST was achieved in the group receiving UDCA (Ursofalk). The results of our study showed that the inclusion of UDCA (Ursofalk) in complex hypoglycemic therapy provides an additional improvement in carbohydrate metabolism. The obtained indicators in the course of the study demonstrate the positive effect of UDCA on weight loss. The greatest result was achieved in reducing waist, which is a positive prognostic factor in reducing the development and progression of NAFLD, diabetes and cardiovascular diseases. Positive changes were observed in relation to the lipid profile. CONCLUSION: The study demonstrated the positive effect of the drug UDCA (Ursofalk) on reducing the degree of liver steatosis, on carbohydrate, lipid metabolism, body weight in patients with DM in combination with NAFLD.
Subject(s)
Diabetes Mellitus, Type 2 , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/drug therapy , Ursodeoxycholic Acid/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Prospective Studies , Reproducibility of Results , Body Weight , Carbohydrates/therapeutic useABSTRACT
Background Imaging studies have limitations in evaluating pancreatic ductal adenocarcinoma (PDAC) treatment response. Purpose To investigate the effectiveness of combined CT and carbohydrate antigen 19-9 (CA 19-9) evaluation at 8 weeks after first-line treatment to predict overall survival (OS) of patients with nonmetastatic PDAC. Materials and Methods Patients with nonmetastatic PDAC who received first-line treatment with either chemotherapy or concurrent chemoradiation in a single-center PDAC cohort registry were retrospectively enrolled in the study between January 2013 and December 2016. Follow-up CT images obtained 8 weeks after treatment were evaluated according to Response Evaluation Criteria in Solid Tumors. Patients with partial response (PR) or stable disease (SD) were defined as CT responders, and those with progressive disease (PD) were defined as CT nonresponders. Patients with a normalized CA 19-9 level at 8-week follow-up were defined as CA 19-9 responders, and those with a nonnormalized or nonelevated CA 19-9 level were defined as CA 19-9 nonresponders. OS was compared using the Kaplan-Meier method with Breslow analysis. Results A total of 197 patients (mean age ± standard deviation, 65 years ± 10; 107 men) were evaluated. Patients with PD (n = 17) showed shorter OS than those with SD (n = 147; P < .001) or PR (n = 33; P = .003). OS did not differ between the patients with PR and those with SD (P = .60). When the CT and CA 19-9 responses were integrated, OS was longest in CT and CA 19-9 responders (group 1, n = 27; median OS, 26.6 months [95% CI: 9.0, 44.1]), followed by CT responders but CA 19-9 nonresponders (group 2, n = 153; median OS, 15.9 months [95% CI: 13.3, 18.5]; P = .007 vs group 1) and CT and CA 19-9 nonresponders (group 3, n = 17; median OS, 6.5 months [95% CI: 0.8, 12.2]; P < .001 vs group 2). Conclusion Integrated evaluation with CT and carbohydrate antigen 19-9 response allowed more accurate stratification of survival in patients with pancreatic ductal adenocarcinoma in the early treatment period than did evaluation according to Response Evaluation Criteria in Solid Tumors. © RSNA, 2022 Online supplemental material is available for this article.
Subject(s)
CA-19-9 Antigen/analysis , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Carbohydrates/therapeutic use , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/drug therapy , Humans , Male , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/drug therapy , Retrospective Studies , Tomography, X-Ray Computed/methods , Treatment Outcome , Pancreatic NeoplasmsABSTRACT
Non-alcoholic fatty liver disease (NAFLD) was defined in 1980 and has the same histological characteristics as alcoholic liver disease except for alcohol consumption. After 40 years, the understanding of this disease is still imperfect. Without specific drugs available for treatment, the number of patients with NAFLD is increasing rapidly, and NAFLD currently affects more than one-quarter of the global population. NAFLD is mostly caused by a sedentary lifestyle and excessive energy intake of fat and sugar. To ameliorate or avoid NAFLD, people commonly replace high-fat foods with high-carbohydrate foods (especially starchy carbohydrates) as a way to reduce caloric intake and reach satiety. However, there are few studies that concentrate on the effect of carbohydrate intake on liver metabolism in patients with NAFLD, much fewer than the studies on fat intake. Besides, most of these studies are not systematic, which has made identification of the mechanism difficult. In this review, we collected and analysed data from studies on human and animal models and, surprisingly, found that carbohydrates and liver steatosis could be linked by inflammation. This review not only describes the effects of carbohydrates on NAFLD and body lipid metabolism but also analyses and predicts possible molecular pathways of carbohydrates in liver lipid synthesis that involve inflammation. Furthermore, the limitations of recent research and possible targets for regulating inflammation and lipogenesis are discussed. This review describes the effects of starchy carbohydrates, a nutrient signal, on NAFLD from the perspective of inflammation.
Subject(s)
Non-alcoholic Fatty Liver Disease , Animals , Humans , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/epidemiology , Liver , Lipogenesis , Inflammation/metabolism , Carbohydrates/pharmacology , Carbohydrates/therapeutic useABSTRACT
The search for a novel prophylactic agent against malaria is on the rise due to the negative socio-economic impact of the disease in tropical and subtropical regions of the world. Sequel to this, we evaluated the in vivo anti-Plasmodium berghei activity of a high-carbohydrate diet as well as the effects of the diet on parasite-associated anemia and organ damage. Mice were fed with either standard or a high-carbohydrate diet for 4 weeks and subsequently infected with chloroquine-sensitive strain of P. berghei. The levels of parasitemia, blood glucose, packed cell volume, and redox sensitive biomarkers of brain and liver tissues were measured. Data from this study showed that high-carbohydrate significantly (p < 0.05) aggravated the multiplication of P. berghei in the animals. Furthermore, our result demonstrated that blood glucose level in P. berghei-infected mice fed with a high-carbohydrate diet was insignificantly (p > 0.05) depleted. Additionally, our findings revealed that high-carbohydrate did not demonstrate a significant (p < 0.05) ameliorative potentials against P. berghei-induced anemia and oxidative stress in the brain and liver tissues. We concluded that high-carbohydrate diet was unable to suppress P. berghei upsurge and accordingly could not mitigate certain pathological alterations induced by P. berghei infection.
Subject(s)
Antimalarials , Malaria , Animals , Antimalarials/pharmacology , Carbohydrates/pharmacology , Carbohydrates/therapeutic use , Malaria/drug therapy , Mice , Oxidative Stress , Parasitemia/drug therapy , Plasmodium bergheiABSTRACT
Multivalent lectin-glycan interactions are widespread in biology and are often exploited by pathogens to bind and infect host cells. Glycoconjugates can block such interactions and thereby prevent infection. The inhibition potency strongly depends on matching the spatial arrangement between the multivalent binding partners. However, the structural details of some key lectins remain unknown and different lectins may exhibit overlapping glycan specificity. This makes it difficult to design a glycoconjugate that can potently and specifically target a particular multimeric lectin for therapeutic interventions, especially under the challenging in vivo conditions. Conventional techniques such as surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) can provide quantitative binding thermodynamics and kinetics. However, they cannot reveal key structural information, e.g., lectin's binding site orientation, binding mode, and interbinding site spacing, which are critical to design specific multivalent inhibitors. Herein we report that gold nanoparticles (GNPs) displaying a dense layer of simple glycans are powerful mechanistic probes for multivalent lectin-glycan interactions. They can not only quantify the GNP-glycan-lectin binding affinities via a new fluorescence quenching method, but also reveal drastically different affinity enhancing mechanisms between two closely related tetrameric lectins, DC-SIGN (simultaneous binding to one GNP) and DC-SIGNR (intercross-linking with multiple GNPs), via a combined hydrodynamic size and electron microscopy analysis. Moreover, a new term, potential of assembly formation (PAF), has been proposed to successfully predict the assembly outcomes based on the binding mode between GNP-glycans and lectins. Finally, the GNP-glycans can potently and completely inhibit DC-SIGN-mediated augmentation of Ebola virus glycoprotein-driven cell entry (with IC50 values down to 95 pM), but only partially block DC-SIGNR-mediated virus infection. Our results suggest that the ability of a glycoconjugate to simultaneously block all binding sites of a target lectin is key to robust inhibition of viral infection.
Subject(s)
Carbohydrates/therapeutic use , Gold/therapeutic use , Hemorrhagic Fever, Ebola/drug therapy , Lectins/therapeutic use , Metal Nanoparticles/chemistry , Molecular Probes/therapeutic use , Polysaccharides/therapeutic use , Binding Sites , Carbohydrates/chemistry , Gold/chemistry , Humans , Lectins/chemistry , Ligands , Molecular Probes/chemical synthesis , Molecular Probes/chemistry , Molecular Structure , Polysaccharides/chemistryABSTRACT
Glycoconjugate vaccines based on bacterial capsular polysaccharides (CPS) have been extremely successful in preventing bacterial infections. The glycan antigens for the preparation of CPS based glycoconjugate vaccines are mainly obtained from bacterial fermentation, the quality and length of glycans are always inconsistent. Such kind of situation make the CMC of glycoconjugate vaccines are difficult to well control. Thanks to the advantage of synthetic methods for carbohydrates syntheses. The well controlled glycan antigens are more easily to obtain, and them are conjugated to carrier protein to from the so-call homogeneous fully synthetic glycoconjugate vaccines. Several fully glycoconjugate vaccines are in different phases of clinical trial for bacteria or cancers. The review will introduce the recent development of fully synthetic glycoconjugate vaccine.
Subject(s)
Bacterial Infections/prevention & control , Carbohydrates/therapeutic use , Polysaccharides/immunology , Vaccines, Synthetic/immunology , Antigens/immunology , Bacterial Capsules/genetics , Bacterial Capsules/immunology , Bacterial Infections/immunology , Bacterial Vaccines/chemistry , Bacterial Vaccines/immunology , Bacterial Vaccines/therapeutic use , Carbohydrates/chemistry , Carbohydrates/immunology , Glycoconjugates/chemistry , Glycoconjugates/immunology , Glycoconjugates/therapeutic use , Humans , Polysaccharides/chemistry , Polysaccharides/therapeutic use , Polysaccharides, Bacterial/chemistry , Polysaccharides, Bacterial/immunology , Vaccines, Conjugate/chemistry , Vaccines, Conjugate/immunology , Vaccines, Conjugate/therapeutic use , Vaccines, Synthetic/chemistry , Vaccines, Synthetic/therapeutic useABSTRACT
Iron deficiency is an important subclinical disease affecting over one billion people worldwide. A growing body of clinical records supports the use of intravenous iron-carbohydrate complexes for patients where iron replenishment is necessary and oral iron supplements are either ineffective or cannot be tolerated by the gastrointestinal tract. A critical characteristic of iron-carbohydrate drugs is the complexity of their core-shell structure, which has led to differences in the efficacy and safety of various iron formulations. This review describes parameters influencing the safety and effectiveness of iron-carbohydrate complexes during production, storage, handling, and clinical application. We summarized the physicochemical and biological assessments of commercially available iron carbohydrate nanomedicines to provide an overview of publicly available data. Further, we reviewed studies that described how subtle differences in the manufacturing process of iron-carbohydrate complexes can impact on the physicochemical, biological, and clinical outcomes of original product versus their intended copies or so-called iron "similar" products.
Subject(s)
Anemia, Iron-Deficiency/drug therapy , Iron Compounds/therapeutic use , Iron/therapeutic use , Nanoparticles/therapeutic use , Administration, Intravenous , Anemia, Iron-Deficiency/pathology , Carbohydrates/chemistry , Carbohydrates/therapeutic use , Humans , Iron/metabolism , Iron Compounds/chemistry , Nanomedicine/trends , Nanoparticles/chemistry , Particle SizeSubject(s)
Adenocarcinoma , Pancreatic Neoplasms , Humans , Neoadjuvant Therapy/adverse effects , Randomized Controlled Trials as Topic , Pancreatic Neoplasms/surgery , Chemoradiotherapy , Carbohydrates/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Pancreatectomy/adverse effectsABSTRACT
The Agency for Healthcare Research and Quality, in partnership with the American College of Surgeons and the Johns Hopkins Medicine Armstrong Institute for Patient Safety and Quality, has developed the Safety Program for Improving Surgical Care and Recovery (ISCR), which is a national effort to disseminate best practices in perioperative care to more than 750 hospitals across multiple procedures in the next 5 years. The program will integrate evidence-based processes central to enhanced recovery and prevention of surgical site infection, venous thromboembolic events, catheter-associated urinary tract infections with socioadaptive interventions to improve surgical outcomes, patient experience, and perioperative safety culture. The objectives of this review are to evaluate the evidence supporting anesthesiology components of colorectal (CR) pathways and to develop an evidence-based CR protocol for implementation. Anesthesiology protocol components were identified through review of existing CR enhanced recovery pathways from several professional associations/societies and expert feedback. These guidelines/recommendations were supplemented by evidence made further literature searches. Anesthesiology protocol components were identified spanning the immediate preoperative, intraoperative, and postoperative phases of care. Components included carbohydrate loading, reduced fasting, multimodal preanesthesia medication, antibiotic prophylaxis, blood transfusion, intraoperative fluid management/goal-directed fluid therapy, normothermia, a standardized intraoperative anesthesia pathway, and standard postoperative multimodal analgesic regimens.
Subject(s)
Anesthesiology/standards , Colorectal Surgery/standards , Patient Safety , Surgical Procedures, Operative/standards , Anesthesia/methods , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Carbohydrates/therapeutic use , Colorectal Neoplasms , Evidence-Based Medicine , Fluid Therapy/methods , Humans , Perioperative Care/standards , Piperidines/therapeutic use , Quality of Health Care , Randomized Controlled Trials as Topic , Safety Management , Thromboembolism , Treatment Outcome , United States , United States Agency for Healthcare Research and Quality , Urinary Tract Infections/diagnosisABSTRACT
PURPOSE: To examine the effect of carbohydrate (CHO) mouth rinsing on endurance running responses and performance in dehydrated individuals. METHODS: In a double blind, randomised crossover design, 12 well-trained male runners completed 4 running time to exhaustion (TTE) trials at a speed equivalent to 70% of VO2peak in a thermoneutral condition. Throughout each run, participants mouth rinsed and expectorated every 15 min either 25 mL of 6% CHO or a placebo (PLA) solution for 10 s. The four TTEs consisted of two trials in the euhydrated (EU-CHO and EU-PLA) and two trials in the dehydrated (DY-CHO and DY-PLA) state. Prior to each TTE run, participants were dehydrated via exercise and allowed a passive rest period during which they were fed and either rehydrated equivalent to their body mass deficit (i.e., EU trials) or ingested only 50 mL of water (DY trials). RESULTS: CHO mouth rinsing significantly improved TTE performance in the DY compared to the EU trials (78.2 ± 4.3 vs. 76.9 ± 3.8 min, P = 0.02). The arousal level of the runners was significantly higher in the DY compared to the EU trials (P = 0.02). There was no significant difference among trials in heart rate, plasma glucose and lactate, and psychological measures. CONCLUSIONS: CHO mouth rinsing enhanced running performance significantly more when participants were dehydrated vs. euhydrated due to the greater sensitivity of oral receptors related to thirst and central mediated activation. These results show that level of dehydration alters the effect of brain perception with presence of CHO.
Subject(s)
Carbohydrates/therapeutic use , Dehydration/drug therapy , Exercise Tolerance , Mouthwashes/therapeutic use , Running , Adult , Anaerobic Threshold , Carbohydrates/administration & dosage , Dehydration/prevention & control , Humans , Male , Mouthwashes/administration & dosage , Organism Hydration StatusSubject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Renal Insufficiency, Chronic , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Diabetic Nephropathies/drug therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Carbohydrates/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Glucose/therapeutic use , KidneyABSTRACT
Glycans are everywhere in biological systems, being involved in many cellular events with important implications for medical purposes. Building upon a detailed understanding of the functional roles of carbohydrates in molecular recognition processes and disease states, glycans are increasingly being considered as key players in pharmacological research. On the basis of the important progress recently made in glycochemistry, glycobiology, and glycomedicine, we provide a complete overview of successful applications and future perspectives of carbohydrates in the biopharmaceutical and medical fields. This review highlights the development of carbohydrate-based diagnostics, exemplified by glycan imaging techniques and microarray platforms, synthetic oligosaccharide vaccines against infectious diseases (e.g., HIV) and cancer, and finally carbohydrate-derived therapeutics, including glycomimetic drugs and glycoproteins.
Subject(s)
Carbohydrates/chemistry , Diagnostic Techniques and Procedures , Drug Discovery/methods , Glycomics/methods , Glycoproteins/chemistry , Vaccines/chemistry , Amino Acid Sequence , Animals , Carbohydrate Sequence , Carbohydrates/pharmacology , Carbohydrates/therapeutic use , Glycoproteins/pharmacology , Glycoproteins/therapeutic use , Humans , Models, Molecular , Molecular Sequence Data , Neoplasms/prevention & control , Vaccines/pharmacology , Vaccines/therapeutic useABSTRACT
Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these.
Subject(s)
Carbohydrates/pharmacology , Food Analysis , Peptides/pharmacology , Animals , Carbohydrates/chemistry , Carbohydrates/therapeutic use , Drug Therapy , Humans , Peptides/chemistry , Peptides/therapeutic use , Plants/metabolismABSTRACT
PURPOSE OF REVIEW: Management of the postoperative response to surgical stress is an important issue in major surgery. Avoiding preoperative fasting using preoperative oral carbohydrates (POC) has been suggested as a measure to prevent and reduce the extent to which such derangements occur. This review summarizes the current evidence and rationale for this treatment. RECENT FINDINGS: A recent review from the Cochrane Collaboration reports enhanced gastrointestinal recovery and shorter hospital stay with the use of POC with no effect on postoperative complication rates. Multiple randomized controlled trials demonstrate improved postoperative metabolic response after POC administration, including reduced insulin resistance, protein sparing, improved muscle function and preserved immune response. Cohort studies in patients undergoing major abdominal surgery have shown that the use of POC as part of an enhanced recovery after surgery protocol is a significant predictor for improved clinical outcomes. SUMMARY: Avoiding preoperative fasting with POC is associated with attenuated postoperative insulin resistance, improved metabolic response, enhanced perioperative well-being, and better clinical outcomes. The impact is greatest for patients undergoing major surgeries.
Subject(s)
Carbohydrates/therapeutic use , Preoperative Care/methods , Administration, Oral , Fasting , Humans , Insulin Resistance , Postoperative PeriodABSTRACT
BACKGROUND: Carbohydrate-rich liquid drinks (CRLDs) have been recommended to attenuate insulin resistance by shortening the preoperative fasting interval. The aim of our study the effect of preoperative oral administration of CRLDs on the well-being and clinical status of patients. METHODS: A randomized, double blind, prospective study of patients undergoing open colorectal operations (CR) and open cholecyctectomy (CH) was conducted. Patients were divided into three groups: study, placebo, and control. Visual analogue scale (VAS) scores for seven parameters (thirst, hunger, anxiety, mouth dryness, nausea, weakness and sleep quality) were recorded and compared for two different time periods (up to 24 h postoperatively and from 36 to 48 h postoperatively). The Simplified Acute Physiology Score changes (SAPS)-II between the three groups were also studied. RESULTS: There were 142 patients American Society of Anesthesiology (ASA) I or II enrolled in the study (CR = 71 and CH = 71). There were no significant differences in postoperative SAPS-II scores or lengths of hospital stay (LOS) between the groups. However, in CR patients, the degree of thirst was partially improved by drinking CRLDs (P = 0.027). In CH patients, on the other hand, feelings of thirst, hunger, mouth dryness, nausea and weakness showed significant improvement (P < 0.05). CONCLUSION: Oral administration of carbohydrate-rich liquid drinks (CRLDs) improves the well-being in patients undergoing CH, but the effect is less evident in patients undergoing CR. No significant improvements were seen in clinical status or in length of hospital stay in either group. TRIAL REGISTRATION: ANZCTR.org.au: ACTRN12614000995673 (registered on 16/09/2014).