Efficacy of ileus tube combined with meglumine diatrizoate in treating postoperative inflammatory bowel obstruction after surgery

BACKGROUND Early postoperative inflammatory small bowel obstruction(EPISBO)is easy to be complicated after colorectal cancer surgery.Both intestinal obstruction catheter and meglumine can treat EPISBO.AIM To investigate the efficacy of an intestinal obstruction tube combined with meg-lumine diazo in treating EPISBO of colorectal cancer.METHODS Data from 60 patients with colorectal cancer and intestinal obstruction admitted to the Proctology Department of our hospital from April 2018 to May 2022 were collected and analyzed and divided into three cohorts according to different treatment regimens.Cohort A(n=20)received a transnasal intestinal obstruction catheter with panumglumine,and cohort B(n=20)received a transnasal intestinal obstruction catheter with liquid paraffin.Cohort C(n=20)received oral treatment with meglumine.The clinical efficacy,first exhaust/defecation time,length of hospital stay,gastrointestinal decompression time,relief time of abdo-minal pain,and relief time of abdominal distension were compared among the three cohorts.The levels of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),monocyte chemotactic protein-1(MCP-1),serum albumin,and transferrin were compared among the three cohorts before and after treatment.The occurrence of adverse reactions in the three cohorts was compared.RESULTS Compared with cohort C,the successful treatment rate of cohort A was signi-ficantly higher.There were statistically significant variations in the time of first exhaust/defecation,length of hospital stays,gastrointestinal decompression time,relief time of abdominal pain,and relief time of abdominal distention among the three cohorts.Compared with cohort C,cohort A’s first exhaust/defecation time,hospitalization time,gastrointestinal decompression time,abdominal pain relief time,and abdominal distension relief time was reduced(P<0.05).After treatment,serum CRP,TNF-α,IL-6,and MCP-1 expression levels increased,and serum albumin and serum transferrin levels increased in the three cohorts.The serum albumin level in cohort A was higher than in cohort C.Compared with cohort B and cohort C,the serum transferrin level in cohort A increased(P<0.05).Compared with cohort C,the total incidence of adverse reactions in cohorts A and B was significantly higher(P<0.05).The incidence of adverse reactions was similar between cohort A and cohort B.CONCLUSION Using an ileus tube combined with meglumine diatrizoate can effectively treat postoperative inflammatory ileus obstructions after surgery colorectal cancer and improve prognosis,inflammatory response,and nutritional status.

Effects of Meglumine Cyclic Adenylate Pretreatment on Systemic inflammatory Response Syndrome Induced by Lipopolysaccharide in Rats

Studies showed that the use of cyclic adenosine monophosphate(cAMP) substitutes or intracellular c AMP activators increased intracellular cAMP level, causing anti-inflammatory effects. This study was to investigate the effects of pretreatment with meglumine cyclic adenylate(MCA), a compound of meglumine and cAMP, on systemic inflammation induced by lipopolysaccharide(LPS) in rats. Eighteen adult male Sprague-Dawley rats were randomly divided into 3 groups(n=6 each): control group(NS group), LPS group(LPS group) and LPS with MCA pretreatment group(MCA group). Systemic inflammation was induced with LPS 10 mg/kg injected via the femoral vein in LPS and MCA groups. In MCA group, MCA 2 mg/kg was injected via the femoral vein 20 min before LPS injection, and the equal volume of normal saline was given in NS and LPS groups at the same time. Three hours after LPS injection, the blood samples were taken from the abdominal aorta for determination of plasma concentrations of TNF-α, IL-1, IL-6, IL-10, cAMP by ELISA and NF-κBp65 expression by Western blotting. The experimental results showed that inflammatory and antiinflammatory indices were increased in LPS group compared to NS group; inflammatory indices were declined and anti-inflammatory indices were increased in MCA group relative to LPS group. Our study suggested that MCA pretreatment may attenuate LPS-induced systemic inflammation.

Pharmacokinetics of Flunixin Meglumine After Intravenous and Intramuscular Administration in Pigs

Pharmacokinetics of flunixin meglumine （FM） was investigated in 14 healthy pigs following single intravenous （i.v.） and intramuscular （i.m.） administration of the drug at the dosage of 2.2 and 1.1 mg kg-1. Blood samples were collected at different intervals after administration, and concentrations of FM were determined by HPLC method with a limit of detection of 0.1μg mL-1. The FM concentration-time data were fitted to a two-compartment open model after single i.v. dosing in pigs. The main pharmacokinetic parameters were as follows： tl/2a, 0.49 ± 0.03 and 0.58±0.07 h; tl/2β, 6.28±0.13 and 7.37 ±0.59 h; V/F, 0.01 ±0.001 and 0.01 ±0.002 L kg-1; CL, 0.01 ± 0.002 and 0.01 ± 0.002 L h-l; AUC, 237.73 ± 52.46 and 147.71 ± 36.76μg h-1 mL-1. The drug concentration-time data were fitted to a two-compartment model with first-order absorption after single i.m. administration in pigs. The main pharmacokinetic parameters were as follows： t1/2α, 0.90± 0.07 and 0.86±0.10 h; t1/2β, 8.79±0.85 and 9.60±0.10 h; V/F, 0.02±0.004 and 0.02±0.003 L kg-1; CL, 0.01±0.002 and 0.01 ±0.003 L h-l; AUC, 174.63 ± 45.84 and 112.42 ± 31.19 pg h-1 mL 1. The results of the present study showed that FM was rapidly absorbed, extensively distributed, and slowly eliminated in pigs. The drug was completely absorbed after single i.m. administration and a good bioavailability in pigs.

广谱抗菌新药——德拉沙星葡甲胺(delafloxacin meglumine)

德拉沙星葡甲胺(delafloxacin meglumine)由日本湧永制药株式会社(Wakunaga Pharmaceutical Co.Ltd.)研制,1996年授予美国RIB-X制药公司全球独家开发权,由该公司旗下Melinta生物制药公司全权负责研发、上市、生产和销售。美国参议院为激励抗菌药物的研发,于2012年6月26日审议通过美国抗菌药物研发法案,即《食品药品管理局安全与创新法案》(FDASIA)。2014年尚处于Ⅲ期临床试验的德拉沙星葡甲胺符合美国食品药品管理局(FDA)制定的"合格的抗感染药品"(QIDP)认证条件,从而获得优先审评待遇,于2017年6月19日获准上市,商品名为Baxdela~。该文对德拉沙星葡甲胺的非临床和临床药理毒理学、临床研究、不良反应、适应证、剂量与用法、用药注意事项及知识产权状态和国内外研究进展等进行介绍。

Safety Study of Flunixin Meglumine Injection on Target Animal Dogs

The study was conducted to evaluate the safety of Flunixin meglumine injection on target animal dogs, and to provide a scientific basis for the dose selec- tion of clinical application. A total of 24 healthy Springer Spaniels were randomly divided into four groups. Intramuscular injection of Flunixin meglumine was carried out to test group dogs with the doses of 2 rag/kg, 6 rag/kg, 10 mg/kg for 5 days, respectively. The injected doses were one times, three times and five times as the recommended clinical dose. Intramuscular injection of water was carried out to control group dogs for 5 days. Clinical symptom was observed after the injection, and the blood was collected at different times （before, during and after the injection） to conduct blood routine examination and blood biochemical indexes measurement. Post-mortem examination and histopathological examination were carried out after the test. The results indicated that test dogs showed normal spirit, with no death and no other adverse reactions. Part values of blood routine examination indexes and blood biochemical indexes in test groups showed significant differences between pre-administration and post-administration, but basically fluctuated within the reference range. Autopsy results showed no obvious pathological changes. Histological examination showed the viscera and tissues （liver, heart, spleen, lung, kidney） in high dose group and control group showed no abnormality and pathological changes. The results indicated that Flunixin meglumine injection with the dose of 2 - 10 rag/kg had a minimal effect on physiological and biochemical indexes of dog blood.

Effect of flunixin meglumine alone and in combination on haemodynamics during bovine endotoxic shock and after treatment

To investigate the effect of Flunixin meglumine- a NSAID;alone and in combination with hypertonic saline on endotoxemic buffalo calves, two groups of five apparently healthy male buffalo calves aged be-tween 6-8 months were subjected to I.V. infusion of E.coli endotoxin at the rate of 5μg/kg BW per hour for 3 hours. A highly significant (P < 0.01) fall in mean systolic,diastolic, pulse, mean arterial pressure (M.A.P), central venous pressure (C.V.P) and haemo-globin was observed till the end of endotoxin infusion while respiratory rate was significantly elevated along with a non-significant alteration in rectal tem-perature and hematocrit during the infusion of en-dotoxin. Immediately at the end of endotoxin infusion, flunixin meglumine at the rate of 1.1 mg/kg B.W was infused i.v. in group-I animals and group-II animals were infused with hypertonic saline solution (H.S.S.) at the rate of 4 ml/Kg BW as one time infusion fol-lowed by flunixin meglumine at the rate of 1.1 mg/kg B.W which resulted in increase of various parameters either to normal or very close to normal value while the rectal temperature and haematocrit decreased non-significantly throughout the observation period of 7 hours. No improvement in Hb and respiration was observed consequent to FM administration. Both treatments successfully raised systolic, diastolic, pulse pressure, C.V.P & M.A.P to normal pre-infusion val-ues. From the results of the present investigation, it can be concluded that i.v. infusion of FM alone and in combination with hypertonic saline solution in en-dotoxemic buffalo calves effectively restores the various hemodynamic parameters close to normal pre-infusion values and it can be used as immediate resuscitation measure to provide the clinician valu-able time to plan further long term treatment.

Cardiovascular Haemodynamics and Some Biochemical Profiles of Endotoxemic Buffalo Calves on Infusion of HSS, Flunixin Meglumine &Blood

Six apparently healthy male buffalo calves aged between 6 months to one year with body weight range of 70 - 140 Kg were used in the present investigation. One animal was used for pilot trial for this group. Five calves were randomly taken into this group. The Eschrechia coli endotoxin infused i/v @5 mg/kg BW/hr for 3 hours to all the animals caused symptoms of restlessness, respiratory distress, snoring, diarrhea, profuse salivation along with the significant fall in systolic, diastolic, pulse and mean arterial venous pressure, hypoproteinemia at 1, 2 & 3 hour and hypoglycemia at 3rd hour i.e., end of endotoxin infusion. Respiration was increased significantly during endotoxin infusion at 2nd & 3rd hour and even afterwards till the end of the observation period i.e. 7 hrs. The treatment with hypertonic saline solution, flunixin meglumine and blood raised (p th, 6th & 7th hour respectively i.e., till the end of the observation period. There was no significant effect on Central Venous Pressure (CVP) and body temperature as measured from rectum.

Effects of Shenmai Injection(参麦注射液)Combined with Meglumine Adenosine Cyclophosphate Injection on Cardiac Function and Peripheral Serum Levels of TNF-α,TGF-β1 and IFN-γ in Patients with Viral Myocarditis

Objective: To explore effects of Shenmai Injection(参麦注射液) combined with Meglumine Adenosine Cyclophosphate Injection on cardiac function and peripheral serum levels of tumor necrosis factor-α(TNF-α), transforming growth factor-β1(TGF-β1) and interferon-γ(IFN-γ) in patients with viral myocarditis.Methods: A total of 70 patients with viral myocarditis admitted in Cardiovascular Medicine Department of our hospital from June 2016 to June 2018 were selected and divided into a control group(treated with Meglumine Adenosine Cyclophosphate Injection) and an observation group(additionally treated with Shenmai Injection(参麦注射液) on the treatment basis of the control group) according to random number method, with 35 cases in each group.Before and after the treatment, cardiac functional indexes like cardiac index(CI), left ventricular ejection fraction(LVEF) and left ventricular shortening fraction(FS), serum levels of TNF-α, TGF-β1 and IFN-γ, clinical efficacy and adverse reactions occurred in the 2 groups were recorded and compared.Results: Therapeutic effective rate in the observation group was 88.57%, higher than 68.57% in the control group(P < 0.05).After the treatment, cardiac functional indexes like CI, LVEF and FS were higher than those in the control group(P < 0.05).After the treatment, the serum expression levels of TNF-α and TGF-β1 were lower than those in the control group(P < 0.05), while the serum expression level of IFN-γ was higher than that in the control group(P < 0.05).There was no statistically significant difference in the adverse reaction rates between the 2 groups(P > 0.05).Conclusion: The treatment of patients with viral myocarditis by Shenmai Injection(参麦注射液) combined with Meglumine Adenosine Cyclophosphate Injection is more effective, reducing inflammation and restoring cardiac function.

Assessment of the potential interactions between favipiravir and radiocontrast agents

BACKGROUND In cases of coronavirus disease 2019(COVID-19),favipiravir is commonly included to the therapy regimen.Drug interactions between favipiravir and other COVID-19 therapy drugs are frequently researched.However,no research on possible drug interactions between Favipiravir and radiocontrast agents,which have become almost crucial in diagnostic processes while not being part of the treatment,has been found.AIM To determine potential medication interactions between Favipiravir and radiocontrast agents.METHODS The study comprised patients who were taking Favipiravir for COVID-19 therapy and underwent a contrast-enhanced computed tomography(CT)or magnetic resonance imaging(MRI)test while taking the medicine.The computerized patient files of the cases included in the study,as well as the pharmacovigilance forms in the designated hospital,were evaluated for this purpose.RESULTS The study included the evaluation of data from 1046 patients.The study sample's mean age was 47.23±9.48 years.The mean age of cases with drug interactions was statistically significant greater than that of cases with no drug interactions(P=0.003).When evaluated with logistic regression analysis,a 1-year raises in age increases the risk of developing drug interactions by 1.63 times(P=0.023).There was no statistically significant difference in the occurrence of medication interactions between the sexes(P=0.090).Possible medication interactions were discovered in 42 cases(4%).CONCLUSION The findings of this study revealed that the most notable findings as a result of the combined use of contrast agents and favipiravir were increased creatinine and transaminase values,as well as an increase in the frequency of nausea and vomiting.The majority of drug interactions discovered were modest enough that they were not reflected in the clinic.Drug interactions become more common as people get older.

Tafamidis meglumine(Vyndaqel)

Tafamidis meglumine由辉瑞公司研发,于2019年5月3日经美国FDA批准上市,商品名为Vyndaqel。该药用于治疗因野生型或遗传性转甲状腺素蛋白介导的淀粉样变性引起的心肌病(ATTR-CM)。该药为20 mg胶囊剂,推荐剂量是每次口服4粒(80 mg),每天一次[1]。Tafamidis meglumine的中文化学名称:2-(3,5-二氯苯基)-1,3-苯并噁唑-6-羧酸单(1-脱氧-1-甲氨基-D-葡萄糖醇);英文化学名称:2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid mono(1-deoxy-1-methylamino-D-glucitol);分子式:C14H7Cl2NO3·C7H17NO5;分子量:503.33;CAS登记号:951395-08-7。

Meglumine catalyzed one-pot green synthesis of novel 4,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-amines

Meglumine efficiently catalyzes the one-pot,five-component reaction of hydrazine,ethyl acetoacetate,aryl aldehydes,substituted phenylacetonitriles and ammonium acetate in ethanol at room temperature to afford novel 4,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-amine derivatives.The present approach offers several advantages such as shorter reaction durations,low cost,excellent yields,milder reaction conditions,simple workup procedure and is environment friendly.All the synthesized derivatives are characterized by IR,^1H NMR,^13C NMR,HRMS and CHN analysis.

Gilbert syndrome combined with prolonged jaundice caused by contrast agent:Case report

This case highlights a patient with Gilbert syndrome who underwent endoscopic retrograde cholangiopancreatography(ERCP) with removal of bile duct stones, who then experienced an unexplained increase in bilirubin, with total bilirubin(TBIL) levels increasing from 159.5 μmol/L to 396.2 μmol/L and to a maximum of 502.8 μmol/L after 9 d. Following the decrease in the TBIL level, enhanced magnetic resonance cholangiopancreatography(MRCP) was performed to exclude any possible remaining choledocholithiasis. Nevertheless, the serum bilirubin level increased again, with TBIL levels rising from 455.7 μmol/L to 594.8 μmol/L and a maximum level of 660.3 μmol/L with no remaining bile duct stones. A liver biopsy showed severe bile duct cholestasis with no inflammation. Based on the exclusion of other potential causes of hyperbilirubinemia and the fact that both instances of increased bilirubin occurred after ERCP and MRCP, the contrast agents iopromide and gadoterate meglumine were suspected to be the causes of the hyperbilirubinemia. As of the writing of this report, the patient's bilirubin levels have spontaneously returned to baseline levels. In summary,ERCP and MRCP utilizing the contrast agents iopromide and gadoterate meglumine may possibly induce prolonged hyperbilirubinemia.

A simple method to improve the dissolution of repaglinide and exploration of its mechanism

In the present study,a simple and rapid method was developed to improve the in vitro dissolution of repaglinide,an oral antidiabetic drug,which was based on addition of meglumine in 50%(v/v)ethanol to dissolve repaglinide,and the drug dissolved in meglumine/50%ethanol was used directly with a binder to prepare tablets.The mechanism of solubilization of repaglinide by meglumine was studied by using infrared spectrum(IR),ultraviolet(UV)measurement through dual wavelength,differential scanning calorimetry(DSC)and X-ray powder diffraction methods.Dissolution tests of repaglinide tablets were performed in the media with different pH values and the repaglinide concentrations were analyzed by High Performance Liquid Chromatography(HPLC)method.The solubility data showed that with the meglumine concentration increasing,the solubility of repaglinide was increased.Meanwhile,tablets with the molar ratio of repaglinide and meglumine 1:2(n/n)resulted in a significant increase in dissolution compared to the repaglinide tablets without using meglumine,and nearly equal to the commercial preparations of Novo-Norm^(®),which concluded that meglumine had a great role in promoting the dissolution of repaglinide.The results of IR and UV dual wavelength methods suggested the formation of repaglinideemeglumine(REPeMEG)molecular complex.DSC results showed that the melting peak of repaglinide disappeared in the REPeMEG coprecipitate,which indicated that repaglinide was stable when existing at amorphous or molecular state.The experiment of X-ray powder diffraction showed that with the solubilization of meglumine,the crystal diffraction peak of repaglinide disappeared,which further inferred that repaglinide was formed complexes with meglumine.It was demonstrated that the method of improving repaglinide with meglumine was reliable and could be suitable for repaglinide tablets production in industry.This study also provides a feasible way to enhance the dissolution of drugs with low solubility,which will be leading to improved bioavailability of these drugs.

A Comparative Evaluation of Different Treatment Regimens in Endotoxemic Buffalo Calves—A Physio-Pathological Perspective

Fifteen apparently healthy male buffalo calves aged between 6 months to one year with body weight range of 70 - 140 Kg divided into 3 groups of 5 buffalo calves each were used in the present investigation. Endotoxic shock was produced by IV infusion of Escherichia coli endotoxin @ 5 μg/kg BW/hr for 3 hours followed by administration of three different treatment regimens comprising of intravenous infusion of hypertonic saline solution(HSS) @ 4 ml/Kg bw, flunixin meglumine @ 1.1 mg/Kg bw and blood @ 20 ml/Kg bw to group-I, HSS, Dextran-40 and Flunixin meglumine to group-II and HSS, Dextran-40, whole blood and Flunixin meglumine to group-III with the objectives to study the major physio-pathological changes during induced endotoxemia in buffalo calves and to compare the effects of different treatment options to find out the best treatment option out of the three combinations. All the animals were further observed up to day 2 or death whichever was earlier. Endotoxin infusion to all the animals caused symptoms of restlessness, respiratory distress, snoring, diarrhoea, profuse salivation along with the significant hypoproteinemia, hypoalbuminemia, hypoglobulinemia, hypokalemia and hypocalcemia. The treatment with HSS, flunixin meglumine and blood infused as one time infusion to these endotoxemic buffalo calves not only alleviated the above mentioned symptoms but also significantly raised the circulating albumin level at 5.5 hrs and day 2 and Fibrinogen level at day 2 of observation. A significant hypocalcaemia was observed at 4.5 hours along with an increase in Alkaline Phosphatase at 3.5, 4.5 and 6.5 hrs. All the endotoxemic buffalo calves which died were subjected to post mortem and histopathological studies. Epicardial and endocardial haemorrhages, haemorrhages on intestinal mucosa, congestion, haemorrhages, emphysema and fibrinous thrombi in microvasculature of lungs were salient histopathological findings. On comparison with observations of the other treatment regimens tried, it was found that the IV infusion of the combination of HSS, Flunixin meglumine, Dextran-40 and blood was found to be the most effective leading to full recovery of 3 out of 5 buffalo calves of group-III where as only 1 out of 5 animals recovered in group-II. None of the group-I animals recovered and all of these succumbed to shock after day-2.

Physio-pathology of induced endotoxaemia in bovine and its treatment regimen

Endotoxic shock was induced in five apparently healthy male buffalo calves by i.v infusion of Escherichia coli endotoxin at 5microgram/kilogram (μg/Kg) body weight/hour (BW/hr) for 3 hours. Endotoxin infusion caused clinical signs of restlessness, respiratory distress, snoring, diarrhoea, profuse salivation along with the significant hypoproteinemia, hypoalbuminemia and hypokalemia in all the animals. The animals were observed up to day 4 or death, whichever was earlier. The treatment with one time intravenous infusion of hypertonic saline solution @ 4milliliter/Kilogram body weight (ml/Kg?BW), dextran-40 @ 10 ml/Kg?BW, flunixin meglumine @ 1.1 milligram/Kg?BW (mg/Kg?BW) and blood @ 20 ml/Kg?BW to these animals alleviated the clinical signs and significantly raised the circulating glucose level at 4.5 and 5.5 hrs. The treatment led to survival of three of the five endotoxemic buffalo calves. The significant hypoproteinemia, hypoalbuminemia, hypokalemia and hypoglobulinemia continued even after treatment. Gross and histopathologic findings of congestion, haemorrhage, necrosis in vital organs viz., lungs, liver, kidneys, brain and intestines were suggestive of endotoxin induced hypoxia and multi-organ failure. Additionally, emphysema and fibrinous thrombi in microvasculature of lungs were salient histopathological findings indicating terminal respiratory failure in the remaining two dead endotoxemic buffalo calves. From clinical signs, plasma chemistry and pathological lesions, it was concluded that endotoxemia led to a disruption of critical life processes, but a timely and effective treatment could counter these deleterious effects and save precious lives.