Lacidipine,thiamine pyrophosphate and their combination on the ocular ischemic syndrome induced by bilateral common carotid artery ligation

AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rats.METHODS:Male albino Wistar rats were categorized as those who underwent sham surgery(SG),right and left common carotid cross-clamping and unclamping procedure(CCU),lacidipine+CCU(LCCU),TPP+CCU(TCCU),and combination of lacidipine and TPP(LTC)+CCU(LTCCU).One hour before anesthesia,the LCCU(n=6)received lacidipine(4 mg/kg,orally)and the TCCU(n=6)received TPP(20 mg/kg,intraperitoneally).The SG(n=6)and CCU(n=6)received the same volume of distilled water from the same route.After anesthesia(60 mg/kg ketamine,intraperitoneally),the necks of the rats were opened in the midline.Ischemia was created for 10min by placing clips on the right and left common carotid arteries.Rats in the SG only underwent subcutaneous incision.After 10min,the clips were removed and reperfusion was achieved for six days.Then,the animals were euthanized(120 mg/kg ketamine,intraperitoneally)and the levels of oxidant,antioxidant and proinflammatory cytokines in the eye tissues were determined.The retinal tissue of the eye was also examined histopathologically.RESULTS:Lacidipine,TPP,and LTC significantly prevent the increase in malondialdehyde,tumor necrosis factoralpha,interleukin-1β(IL-1β),and IL-6 levels,decrease in total glutathione levels,superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in rats.The impact of these drugs on protection is determined to be LTC>lacidipine>TPP.CONCLUSION:As a result of the study,it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.

Volumetric and ultrasonic properties of thiamine hydrochloride drug in aqueous solutions of choline-based deep eutectic solvents at different temperatures

Important efforts have been made over the past years to improve the drug acts,which leads to the discovery of novel drug preparations and delivery systems.The optimal design of such processes requires a molecular-level understanding of the interactions between drug molecules and biological membranes.The thermodynamic investigation provides deep and complete knowledge of interactions and the choice of appropriate and suitable production compounds in pharmaceutical fields.Particularly,the analysis of drugs+co-solvents in aqueous media is the central issue in many types of research because they exert their impact by interacting with biological membranes.This work is aimed to measure the density and speed of sound for the thiamine hydrochloride in water+deep eutectic solvents(DESs)mixtures(choline chloride/urea,choline chloride/ethylene glycol and choline chloride/glycerol)at temperature range(293.15-308.15)K.By correlation of the evaluated parameters in some standard relations,the partial molar parameters i.e.apparent molar volumes,Vφ,m,and apparent molar isentropic compression,κ_(s,φ,m),are calculated.In addition,apparent molar isobaric expansion,E^(0)_(φ,m),and Hepler’s constant are computed from the density and speed of sound data.For fitting the experimental Vφ,m andκ_(s,φ,m)the Redlich-Meyer equation was employed that the important quantities;standard partial molar volume,V^(0)_(m),and partial molar isentropic compression,κφ,m0,were obtained.The thermodynamic analysis of the studied system also plays a crucial role in the pharmaceutical industry.

The Protective Effect of Ascorbic Acid and Thiamine Supplementation against Damage Caused by Lead in the Testes of Mice

Lead is a ubiquitous environmental and industrial pollutant that may have toxic effects on the male. Vitamins may protect against toxic effects of lead in the liver and reproductive system, which is confirmed by our initial research. The aim of this study was to further investigate the protective effects of vitamins （ascorbic acid combined with thiamine） on lead acetate （Pb）-induced reproductive toxicities in mice and study the possible mechanisms underlying these effects. Forty-five male mice were randomly divided into 3 groups, 15 mice in each and received daily intragastric administration with control, Pb （20 mg/kg）, and Pb＋vitamins （ascorbic acid of 420 mg/kg＋thiamine of 30 mg/kg） for 6 weeks, respectively. The Pb-treated animals showed significant decreases in the epididymal sperm count and motility compared to the control group, while the Pb＋vitamins group had significant increases for these variables. Moreover, an increasing apoptosis of germinal cells induced by Pb was reduced by vitamin treatment. Pb induced the activation of Caspase-3, Fas/Fas-L and Bcl-2 with elevated levels, and the adaptor protein primarily regulated signaling through Fas and required for Fas-induced apoptosis. In conclusion, ascorbic acid combined with thiamine exhibited protective effect on reproductive system by inhibiting Pb-induced excessive cell apoptosis.

Effects of thiamine on Trichothecium and Alternaria rots of muskmelon fruit and the possible mechanisms involved

The effects of thiamine against pink and black spot rots caused by Trichothecium roseum and Alternaria alternata and modulation on the metabolism of reactive oxygen species （ROS） and phenylpropanoid pathway were investigated in this paper. In vitro test indicated that thiamine significantly inhibited mycelia growth and spore germination of T. roseum and A. alternata. Thiamine at 100 mmol L-1 effectively inhibited lesion development of muskmelon fruit inoculated with T. roseum or A. alternata, enhanced production rate of O2; and H2O2 content, activities of catalase （CAT）, ascorbate peroxidase （APX） and glutathione reductase （GR） in muskmelon fruit. Thiamine also affect phenylpropanoid pathway in muskmelon fruit by increasing the activities of phenylalanine ammonia lyase （PAL） and peroxidase （POD）, the content of total phenolic compounds, flavonoids and lignin. These results suggest that the effects of thiamine on pink and black spot rots in muskmelon fruits are associated with its direct fungitoxic against the pathogens and the modulation of O2- and H2O2 production, elimi- nating enzymes and phenylpropanoid pathway.

Experimental evaluation of thiamine as a new clay swelling inhibitor

This study aims at evaluating the performance of thiamine as a new eco-friendly shale inhibitor in water-based drilling fluids(WBDFs).The evaluation experiments include sedimentation,bentonite inhibition,filtration,zeta potential,thermal gravimetric analysis,scanning electron microscopy,X-ray diffraction,shale cuttings recovery,linear swelling and Fourier transform infrared spectroscopy(FTIR).The performance of thiamine was compared to potassium chloride.In contrast to deionized water,the aqueous solution of thiamine exhibited greater power to inhibit montmorillonite(Mt)dispersion,much more Mt loading capacity(280 g/L)and fluid loss,lower Mt mass loss,larger aggregated Mt particles,lower interlayer space of the Mt particles,less shale cuttings disintegration and lower linear swelling.Adsorption of thiamine on Mt led to a significant shift in the value of zeta potential(from-17.1 to+8.54 mV).Thiamine demonstrated superior inhibitive performance than potassium chloride.FTIR analysis confirmed that thiamine is adsorbed on Mt particles.The compatibility test revealed the compatibility of thiamine with conventional WBDF additives.It was concluded that the main probable inhibition mechanisms of thiamine are the cation exchange and Mt surface coating.In view of its prominent inhibition capacity and great environmental acceptability,thiamine is a promising inhibitor for drilling in water-sensitive formations.

Evidence for altered thiamine metabolism in diabetes: Is there a potential to oppose gluco- and lipotoxicity by rational supplementation?

Growing prevalence of diabetes(type 2 as well as type 1) and its related morbidity due to vascular complications creates a large burden on medical care worldwide. Understanding the molecular pathogenesis of chronic micro-, macro- and avascular complications mediated by hyperglycemia is of crucial importance since novel therapeutic targets can be identified and tested. Thiamine(vitamin B1) is an essential cofactor of several enzymes involved in carbohydrate metabolism and published data suggest that thiamine metabolism in diabetes is deficient. This review aims to point out the physiological role of thiamine in metabolism of glucose and amino acids, to present overview of thiamine metabolism and to describe the consequences of thiamine deficiency(either clinically manifest or latent). Furthermore, we want to explain why thiamine demands are increased in diabetes and to summarise data indicating thiamine mishandling in diabetics(by review of the studies mapping the prevalence and the degree ofthiamine deficiency in diabetics). Finally, we would like to summarise the evidence for the beneficial effect of thiamine supplementation in progression of hyperglycemia-related pathology and, therefore, to justify its importance in determining the harmful impact of hyperglycemia in diabetes. Based on the data presented it could be concluded that although experimental studies mostly resulted in beneficial effects, clinical studies of appropriate size and duration focusing on the effect of thiamine supplementation/therapy on hard endpoints are missing at present. Moreover, it is not currently clear which mechanisms contribute to the deficient action of thiamine in diabetes most. Experimental studies on the molecular mechanisms of thiamine deficiency in diabetes are critically needed before clear answer to diabetes community could be given.

Hydrocortisone, ascorbic acid and thiamine for sepsis: Is the jury out?

Sepsis and septic shock remain a major cause of morbidity and mortality among patients admitted in the intensive care unit.Diabetes is a major risk factor for the development of sepsis.The global mortality of sepsis remains high,despite significant interventions and guidelines.It has been known for decades that patients with sepsis have reduced levels of antioxidants,most notably vitamin C.Furthermore,experimental data has demonstrated multiple beneficial effects of vitamin C in sepsis.In addition,corticosteroids and thiamine may have synergistic biological effects together with vitamin C.Preliminary data suggests that therapy with hydrocortisone,ascorbic acid and thiamine improves the outcome of patients with sepsis with the potential to save millions of lives.However,this intervention has met with much resistance and has not been widely adopted.Ultimately,we await the final jury verdict on this simple,safe and cheap intervention.

Sociodemographic Factors Associated with Dietary Intake of Thiamine, Riboflavin, and Niacin among Chinese Adults in 2015

Objective To estimate the association between three B-vitamin intakes and sociodemographic factors among adults in China.Methods We derived our data from the China Health and Nutrition Survey(CHNS) among 12,241 individuals aged 18–64 years. Log binomial regression was used to estimate adjusted prevalence ratios for factors associated with the inadequate intake of B-vitamins.Results Females with low incomes and living in the north had a higher prevalence of inadequate riboflavin intake than those with high incomes and living in the south. Both males and females living in a village had a higher prevalence of inadequate riboflavin intake than adults living in a city. Adults with low income, low education, and living in the north or in a village had a higher prevalence of inadequate niacin intake than adults with a high income, high education, and living in the south or in a city.Conclusion We found that income, region, and area of residence were associated with riboflavin intake. Education, income, region, and area of residence were associated with niacin intake. Welltailored strategies and policies are needed to improve nutritional status in China.

Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1？

Myotonic dystrophy type 1, also known as Steinert＇s disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine （vitamin B1） is a cofactor of fundamental enzymes involved in the energetic cell me- tabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We de- scribed two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council （MRC）, the Muscular Impairment Rating Scale （MIRS）, and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients＇ activi- ties of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2-4 in the distal muscles （the MRG score before the treatment was 3-4 and 1-3, re- spectively）. The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment.

SIMULTANEOUS DETERMINATION OF VITAMIN B COMPLEX (THIAMINE, RIBOFLAVIN, NIACIN, PYRIDOXINE AND FOLIC ACID) IN FOODS BY HPLC

A high performance liquid chromatographic assay has been developed for the simultaneous determination of five water soluble vitamins:thimine, riboflavin, niacin, pyridoxine and folic acid in cereal products and fresh vegetables. Food samples were hydrolyzed in 0.4 mol/L HCl, autoclaved at 120℃ 15 psi for 20 minutes, using a μ-Bondapak column (3.9×300mm, Waters Co.), a mobile phase of methanol-water (30:70) (0.005 mol/L heptanesulfonic acid) and a flow rate of 1.0 ml/min gave the most satisfactory separation of the five water soluble vitamins. A double channel deteetion was used: four vitamins (B_5, folic acid, B_2, B_1) were detected hy UV spectrophotometry (254 nm) first, pyridoxine (B_6) was detected by fluoromelry (EX 290nm, EM 395 nm) afterwards. Detection limits were 2, 5, 5, 2and 5ng, linear ranges were 5-10ng, 5-50ng, 5-40ng, 5-50ng and 10-50ng for B_1, B_2, B_5, B_6 and folic acid respectively. Recoveries were 92-100%(B_5), 51-52% (folio acid), 103—105% (B_2), 99—100% (B_6) and 91.3—102% (B_1) respectively. In comparison with a reference method and checking with food composition tables, very satisfactory results were obtained by this method.

Gene expression and histopathological evaluation of thiamine pyrophosphate on optic neuropathy induced with ethambutol in rats

AIM： To compare the effects of thiamine pyrophosphate（TPP） and thiamine（TM） in oxidative optic neuropathy in rats induced by ethambutol.METHODS： The animals were divided into four groups：a control group（CG）,an ethambutol control（ETC） group,TM plus ethambutol group（TMG）,and TPP plus ethambutol group（TPPG）.One hour after intraperitoneal administration of TM 20 mg/kg to the TMG group and TPP 20 mg/kg to TPPG group,30 mg/kg ethambutol was given via gavage to all the groups but the CG.This procedure was repeated once daily for 90 d.After that period,all rats were exposed to high levels of anaesthesia in order to investigate the gene expression of malondialdehyde and glutathione in removed optic nerve tissue and histopathologically to examine these tissues. RESULTS： Malondialdehyde gene expression significantly increased,whereas glutathione gene expression significantly decreased in the ETC group compared to the CG.TM could not prevent the increase of malondialdehyde gene expression and the decrease of glutathione,while TPP significantly could suppress.Histopathologically,significant vacuolization in the opticnerve,single-cell necrosis in the glial cells,and a decrease in oligodendrocytes were observed in the ETC group.Vacuolization in the optic nerve,a decrease in oligodendrocytes and single-cell necrosis were found in the TMG group,while no pathological finding was observed in the TPPG group except for mild vacuolization.CONCLUSION： TPP protects the optic nerve against the ethambutol-induced toxicity but TM does not.TPP can be beneficial in prophilaxis of optic neuropathy in ethambutol therapy.

Validation of a HPLC Method for Quantification of Thiamine and Its Phosphate Esters in Rat Brain Tissue

The present data show a fast and efficient biological sample processing method for the extraction of thiamine (vitamin B1) and its mono-(TMP) and di-(TDP) phosphate esters from hippocampus, thalamus and prefrontal cortex (PFC) and blood sample of the rodents. In addition, using the hippocampus and standards of these three compounds we validated an isocratic fluorescence HPLC procedure for a simultaneous detection of them in a single chromatogram within a total run time of about 12 min. Reproducibility for TDP, TMP and B1 was 2.66%, 4.50% and 7.43% (intraday) and 37.54%, 25.39% and 25.87% (interday), respectively. Recovery assays were between 96.0% and 101.7%. The calibration curves were linear and the concentrations of the three compounds, all in nanomolar range, were determined in the brain areas and in the blood samples. When compared to the current methods in the literature, this new method provides information on essential variables, such as linearity range and limit of detection, reproducibility and stability of thiamine, TMP and TDP in rat brain samples. The present data on sample processing and B1 and its phosphate ester level determinations are the first to be validated using hippocampus samples of rats.

Psychogenic anorexia and non-alcoholic Wernicke's encephalopathy: Complete clinicoradiological recovery with thiamine

Rationale:Prolonged undernutrition may arise out of depression and lead to Wernicke's encephalopathy if timely diagnosis and intervention are missed.Wernicke's encephalopathy is potentially treatable,and appropriate treatment may revert clinical depression and cognitive dysfunction to some extent.Patient's concern:A 69-year-old female who had been taking escitalopram for one year developed tremor,ophthalmoplegia,ataxia,progressive cognitive decline,and convulsions.Diagnosis:Non-alcoholic Wernicke's encephalopathy and hypomagnesemia due to psychogenic anorexia.Interventions:High dose intravenous thiamine and magnesium were supplemented.Outcomes:The patient showed remarkable improvement in neurological complications and even in depressive features.Lessons:Wernicke's encephalopathy should not be ignored in the treatment of depression.

Normal and reverse flow injection-spectrophotometric determination of thiamine hydrochloride in pharmaceutical preparations using diazotized metoclopramide

Simple and sensitive normal and reverse flow injection methods for spectrophotometric determination of thiamine hydrochloride （THC） at the microgram level were proposed and optimized. Both methods are based on the reaction between THC and diazotized metoclopramide in alkaline medium. Beer＇s law was obeyed over the range of 10 300 and 2-90 ug/mL, the limits of detection were 2.118 and 0.839 ug/mL and the sampling rates were 80 and 95 injections per hour for normal and reverse flow injection methods respectively. The application of both methods to commercially available pharmaceuticals produced acceptable results. The flow system is suitable for application in quality control processes.

Effects of 17<i>β</i>-Estradiol on Dopamine D2 Receptors in Thiamine-Deficient Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Our previous studies showed that 17β-estradiol (E2) modulated dopamine D2 receptor in regulating body weight set-point. The aim of this study was to understand whether thiamine deficiency influenced the E2 modulation on dopamine D2 receptors, using bromocriptine mesylate (BR) and sulpiride (SUL) as selective central dopamine-D2 receptors agonist and antagonist respectively. We studied the E2-dopamine D2 receptors interferences in a 10-day thiamine-deficient female rats for which consumptions of water, sugar, alcohol and food were daily-recorded and their consequences on body weights assessed. Our results showed that the volume of water daily ingested doubled in thiamine-deficient female rats (OXT), while sugar and alcohol consumptions collapsed with decreased weight and food consumption. On the one hand, thiamine potentiated D2/BR activity (bromocriptine-activated D2 receptors) to induce sugar intake and inhibited the same D2/BR receptors to induce water intake. On the other hand, thiamine promoted D2/SUL receptors (sulpiride-inhibited D2 receptors) for enhanced alcohol intake, increased food consumption and weight gain. Taking together, thiamine modulated the actions of 17β-estradiol on both D2/BR and D2/SUL receptors activities.

Can Wernicke’s Encephalopathy Be Precipitated by Administering Glucose before Thiamine in Severely Malnourished or Alcoholic Patients?

We discuss the safety and controversy regarding the administration of glucose before thiamine with regards to precipitation of Wernicke’s Encephalopathy in the severely malnourished and alcoholic patient population. Herein we review clinical features, pathophysiology and the relevant literature to provide an evidenced-based recommendation that thiamine replacement should not delay glucose administration acutely in the malnourished patient population.

The Impact of Thiamine Treatment on Generalized Anxiety Disorder

Objective: Patients with generalized anxiety disorder (GAD) are fearful. They constantly worried about minor matters, and they anticipate the worst. The GAD is diagnosed when a patient experiences excessive anxiety and worry for at least 6 months. The cause of GAD is unknown. In the present paper, we discuss patients with GAD who have low levels of thiamine in their bloods. We also discuss the role of thiamine in the pathogenesis and treatment of GAD. Methods: We examined 9 patients (6 males and 3 females) who met the DSM-IV-TR diagnostic criteria for GAD. These patients had no history of alcoholism. Their ages ranged from 57 to 83 years old (mean age –72.8 ± 2.9 years). All of the patients had low blood thiamine levels (mean –25.1 nmol/L ± 6.0 nmol/L;normal level—70 nmol/L - 180 nmol/L). Participants completed the Hamilton Anxiety Rating Scale (HARS) for anxiety before and after thiamine treatments. All of the patients received daily thiamine 100 mg intramuscularly. Results: Thiamine supplementation significantly improved HARS scores, increased both appetite and general well-being, and reduced fatigue in patients with GAD. Interestingly, these patients were able to discontinue taking anxiolytic and β-blocker medications. Conclusion: Parental thiamine significantly affects patients with GAD.

Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata(Desv.)Spring against inflammatory bowel disease

Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is necessary.An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of→4)-α-d-GalAp-(1→and→6)-β-d-Galp-(1→and the branched structure of→5)-α-l-Araf-(1→.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes.Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism study.Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model group.In conclusion,SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD.This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

Hydrocortisone,vitamin C,and thiamine may not improve the outcome of patients with sepsis or septic shock:a systematic review and meta-analysis

Background This study aimed to conduct a systematic review and meta-analysis of the efficacy of hydrocortisone,vitamin C,and thiamine(HVT)in patients with sepsis or septic shock.Methods A literature search was performed in PubMed,Embase,Cochrane Library,and Web of Science from their inception to April 2021.Search terms included hydrocortisone,thiamine,vitamin C,sepsis,and septic shock.Only randomized controlled trials on HVT in treating sepsis and septic shock were analyzed.Risk ratio(RR)was generated using Review Manager 5.3 to evaluate binary variants,whereas mean±standard deviation(MD)was generated to assess continuous variants.Results A total of 7 randomized controlled trials,with 1233 patients,were included in this meta-analysis.There was no significant difference in long-term mortality(35.3%vs 33.2%;RR:1.07;95%confidence interval[95%CI]:0.90-1.27;P=0.45;I^(2)=0%),intensive care unit(ICU)mortality(17.4%vs 17.5%;RR:0.99;95%CI:0.75-1.30;P=0.95;I^(2)=0%),in-hospital mortality(27.4%vs 25.8%;RR:1.06;95%CI:0.84-1.34;P=0.63;I^(2)=0%),and acute kidney injury morbidity(RR:1.04;95%CI:0.91-1.18;P=0.60;I^(2)=0%)between HVT and control groups.For continuous variables,there was no significant effect of HVT therapy on delta Sequential Organ Failure Assessment(△SOFA)score(MD:−0.44;95%CI:−1.00 to 0.12;P=0.12;I^(2)=49%),length of ICU stay(MD:0.43;95%CI:−0.27 to 1.14;P=0.23;I^(2)=0%),and length of hospital stay(MD:0.80;95%CI:−0.38 to 1.97;P=0.18;I^(2)=0%).Only vasopressor duration was significantly reduced in the HVT group(MD:−17.75;95%CI:−25.56 to−9.94;P<0.00001;I^(2)=38%).Vasopressor duration refers to the time to shock reversal.Alternatively,it is the amount of time(in hours)required for patients to withdraw all vasoactive medication support.Neither HVT nor control△SOFA reached statistical significance.Conclusion Hydrocortisone,vitamin C,and thiamine use was not associated with improved mortality,lower acute kidney injury incidence,lower△SOFA,and shorter ICU and in-hospital stays among patients with sepsis and septic shock.However,the use of vasopressors decreased significantly.Further direct head-to-head studies are needed.

Biomimetic thiamine- and niacin-decorated liposomes for enhanced oral delivery of insulin

Biomimetic nanocarriers are emerging as efficient vehicles to facilitate dietary absorption of biomacromolecules. In this study, two vitamins, thiamine and niacin, are employed to decorate liposomes loaded with insulin, thus facilitating oral absorption via vitamin ligand–receptor interactions. Both vitamins are conjugated with stearamine, which works to anchor the ligands to the surface of liposomes.Liposomes prepared under optimum conditions have a mean particle size of 125–150 nm and an insulin entrapment efficiency of approximately 30%–36%. Encapsulation into liposomes helps to stabilize insulin due to improved resistance against enzymatic disruption, with 60% and 80% of the insulin left after 4 h when incubated in simulated gastric and intestinal fluids, respectively, whereas non-encapsulated insulin is broken down completely at 0.5 h. Preservation of insulin bioactivity against preparative stresses is validated by intra-peritoneal injection of insulin after release from various liposomes using the surfactant Triton X-100. In a diabetic rat model chemically induced by streptozotocin, both thiamine-and niacindecorated liposomes showed a comparable and sustained mild hypoglycemic effect. The superiority of decorated liposomes over conventional liposomes highlights the contribution of vitamin ligands. It is concluded that decoration of liposomes with thiamine or niacin facilitates interactions with gastrointestinal vitamin receptors and thereby facilitates oral absorption of insulin-loaded liposomes.