急性早幼粒细胞白血病患者止血和凝血分子标志物的检测分析

目的:检测急性早幼粒细胞白血病(APL)患者止血和凝血分子标志物含量变化及其临床意义。方法:采用ELISA方法检测46例APL患者于化疗前和完全缓解后的血浆血小板α颗粒膜糖蛋白-140(GMP-140)、D-二聚体(D-D)、凝血酶-抗凝血酶复合物(TAT)、凝血酶原片段F1+2、纤溶酶-抗纤溶酶复合物(PAP)含量,并与38例正常人对照。结果:化疗前46例APL患者血浆TAT、D-D、F1+2、GMP-140、PAP含量明显高于正常对照组(P<0.05~0.01),完全缓解后GMP-140、TAT、D-D、F1+2、PAP水平恢复正常;未缓解和复发患者GMP-140、TAT、D-D、F1+2、PAP水平与初诊患者无明显差异(P>0.05)。结论:APL患者凝血系统激活、纤溶亢进,但随病情好转可逐渐改善。止血和凝血分子标志物检测有助于APL病情和疗效观察。     

Influence of training on markers of platelet activation in response to a bout of heavy resistance exercise

Recent connections between platelet activity and cardiovascular disease have raised questions of whether platelet function varies in exercising individuals. Resistance training has been linked to a possible reduction in hyper-aggregability of platelets, especially following acute strenuous exercise. The present investigation was designed to explore the effects of an acute resistance exercise test on the primary hemostatic system in both resistance-trained (RT) and untrained (UT) individuals. Ten RT (five men and five women; age, 26.0 ± 4.5 years; height, 175.12 ± 8.54 cm; weight, 79.56 ± 13.56 kg) and ten UT (five men and five women; age, 26.4 ± 6.2 years; height, 170.31 ± 7.45 cm; weight 67.88 ± 16.90 kg) individuals performed an Acute Exhaustive Resistance Exercise Test (AERET; six sets of ten repetitions of squats at 80 % of the 1-Repetition Maximum (RM)). Blood samples were obtained before, immediately after, and at 15, 60, and 120 min following the AERET. Blood samples were analyzed for platelet count, von Willebrand factor antigen (vWF:Ag), beta-thromboglobulin (β-TG), and platelet factor 4 (PF4). B-TG showed significant differences (p < 0.05) between RT and UT at +15 and +60 min. Both groups showed a main effect for time in platelet count, vWF, and β-TG following the AERET, whereas PF4 remained unchanged. All blood variables returned to baseline 120 min after exercise. Compared with UT, RT demonstrated reduced platelet activation in response to an acute bout of heavy resistance exercise. Reduced platelet activation may be attributed to training status, as shown by a reduction in plasma concentrations of B-TG in the RT group.     

Effect of an ionic compared to a non-ionic X-ray contrast agent on platelets and coagulation during diagnostic cardiac catheterisation

The aim of the present study was to evaluate the effects of ionic (ioxaglate) and non-ionic (iopromide) contrast media on haemostatic parameters ex vivo. In 40 patients undergoing coronary angiography, platelet function (platelet reactivity and serotonin concentration) and coagulation markers [thrombin-antithrombin III complexes, prothrombin fragments (F1+2) and the D-dimers] were measured. The use of an ionic X-ray contrast agent (XCA) (ioxaglate) in diagnostic cardiac catheterisation angiography is associated with lower thrombin generation and lower activation of the platelet system than when a non-ionic XCA is employed (iopromide). The results thus confirm the results of various in vitro studies and animal investigations.     

Quantitative Dual Contrast CT Technique for Evaluation of Articular Cartilage Properties

Impact injuries of cartilage may initiate post-traumatic degeneration, making early detection of injury imperative for timely surgical or pharmaceutical interventions. Cationic (positively-charged) CT contrast agents detect loss of cartilage proteoglycans (PGs) more sensitively than anionic (negatively-charged) or non-ionic (non-charged, i.e., electrically neutral) agents. However, degeneration related loss of PGs and increase in water content have opposite effects on the diffusion of the cationic agent, lowering its sensitivity. In contrast to cationic agents, diffusion of non-ionic agents is governed only by steric hindrance and water content of cartilage. We hypothesize that sensitivity of an iodine(I)-based cationic agent may be enhanced by simultaneous use of a non-ionic gadolinium(Gd)-based agent. We introduce a quantitative dual energy CT technique (QDECT) for simultaneous quantification of two contrast agents in cartilage. We employ this technique to improve the sensitivity of cationic CA4+ (q?=+4) by normalizing its partition in cartilage with that of non-ionic gadoteridol. The technique was evaluated with measurements of contrast agent mixtures of known composition and human osteochondral samples (n?=?57) after immersion (72 h) in mixture of CA4+ and gadoteridol. Samples were arthroscopically graded and biomechanically tested prior to QDECT (50/100 kV). QDECT determined contrast agent mixture compositions correlated with the true compositions (R²=?0.99, average error?=?2.27%). Normalizing CA4+ partition in cartilage with that of gadoteridol improved correlation with equilibrium modulus (from ρ?=?0.701 to 0.795). To conclude, QDECT enables simultaneous quantification of I and Gd contrast agents improving diagnosis of cartilage integrity and biomechanical status.     

Adverse reactions during procedures: Hypersensitivity to contrast agents and dyes

ObjectiveThis review provides an overview of the literature on hypersensitivity reactions during procedures to commonly used contrast agents and dyes. A synthesis of current knowledge on clinical symptoms, epidemiology and risk factors, pathomechanism, and management of hypersensitivity reactions to these substances is presented.Data SourcesA literature search was conducted through Medline. Included were peer-reviewed articles written in English between 2000 and 2019.Study SelectionsRelevant clinical studies, experimental studies, and review articles have been selected. Additionally, case reports have been included if they carried significant information about rare clinical forms of hypersensitivity reactions, disease mechanisms, or therapy.ResultsAn allergological workup is only indicated for patients with a history of immediate (IHR) and nonimmediate hypersensitivity reactions (NIHR) but not for toxic or unrelated adverse events. Skin tests with or without experimental cellular laboratory tests in patients with previous reactions can provide evidence for an allergic mechanism. Positive skin tests indicating allergy are more common in severe reactions. If the adverse event was allergic, skin testing of alternatives is helpful for the selection of other contrast agents for future procedures. Premedication alone may be insufficient in these cases, and breakthrough reactions occur. For nonallergic reactions, change of contrast agent and premedication is often but not always sufficient to suppress reactions.ConclusionPatients with previous NIHR or IHR, especially moderate and severe IHR, needing potential re-administration of contrast agents should be skin tested to identify an allergic mechanism as well as alternative agents to be used for future procedures.     

冠状动脉介入诊疗中不同剂量非离子型对比剂对肾功能的影响

目的探讨冠状动脉介入诊疗中不同剂量非离子型对比剂对肾功能的影响。方法选择行冠状动脉介入诊疗术(冠状动脉造影和/或冠状动脉支架植入术)的患者500例,其中男性280例,女性220例;年龄53～78岁,平均年龄65.0岁。单纯冠状动脉造影280例,冠状动脉造影+冠状动脉支架植入术220例。根据使用非离子型对比剂的剂量随机分为3组:低剂量组(<100 mL)180例,其中男性100例,女性80例,平均年龄60.2岁;中剂量组(100～200 mL)200例,男性110例,女性90例,平均年龄65.6岁;高剂量组(>200 mL)120例,男性70例,女性50例,平均年龄66.9岁。分别检测各组对比剂应用前及应用后8、12、24、48、72 h反映肾功能情况的血清肌酐(SCr)、胱抑素C(Cys C),比较每组内和组间不同时间段的SCr、Cys C。结果低剂量组中,SCr仅在对比剂应用后48 h升高,而Cys C仅在对比剂应用后24 h升高,且差异具有统计学意义(P<0.05),其他时段均与基线水平差异无统计学意义。与低剂量组相比,中剂量组血SCr、Cys C在各个时间段升高幅度明显增加(P<0.05),而高剂量组比中剂量组SCr、Cys C在各个时间段进一步升高(P<0.05),并且随着对比剂应用剂量的增加,如中剂量组和高剂量组其SCr、Cys C升高的程度均明显提高,差异具有统计学意义(P<0.05),且恢复速度明显变慢,部分患者对比剂应用72 h后仍未恢复到基线水平,并且较基线水平明显升高(P<0.05)。结论在冠状动脉介入诊疗中,应用非离子型对比剂对肾功能的损害与对比剂剂量明显相关,低剂量(<100 mL)对肾功能影响小且恢复快,而中剂量(100～200 mL)和高剂量(>200 mL)随着剂量的增加其对肾功能的影响越大,且恢复越慢,部分患者由对比剂造成的肾功能损害在一定时间内持续存在。     

In vitro andin vivo studies of radiographic contrast media-induced histamine release in pigs

Routine clinical use of radiographic contrast media (RCM) causes adverse reactions in some patients. To elucidate the mechanisms of these reactions bothin vitro andin vivo studies are necessary. In this study, RCM-induced histamine release from isolated mast cells was compared with thein vivo release of histamine and cardiovascular symptoms using a porcine model. The 2 non-ionic preparations examined (Solutrast^® and Ultravist^®) released little or no histamine from the 4 cell types tested (porcine pulmonary, cardiac, hepatic, and renal mast cells). The 4 ionic preparations (Angiographin^®, Hexabrix^®, Rayvist^®, and Telebrix^®) caused histamine release from most of the cell suspensions. In almost all cases, the cardiac mast cells were the most sensitive followed by the hepatic mast cells. All 4 RCM testedin vivo produced elevated plasma histamine levels in some animals. The highest incidence was observed using the ionic, high osmolal Rayvist^® (6 of 12 animals), followed by the non-ionic RCM with the lowest osmolality Ultravist^® (4 of 12 animals).In vivo, mechanisms in addition to direct histamine release may also be involved in RCM-induced adverse reactions, since low osmolal, non-ionic RCM can cause elevated plasma histamine levels withoutin vitro release. The susceptibility of cardiac mast cells to RCM-induced histamine release suggests that patients undergoing e.g. coronary angiography may be especially at risk for an adverse reaction.     

Die Bedeutung des Thrombin-Antithrombin III-Komplexes in der Diagnostik der Lungenembolie und der tiefen Venenthrombose — Vergleich mit Fibrinopeptid A,Plättchenfaktor 4 und β-Thromboglobulin

Summary In 22 patients with suspected pulmonary embolism and 19 patients with suspected deep vein thrombosis, thrombin-antithrombin III complex (TAT) as an indicator of thrombin activation was measured using a newly developed ELISA. For comparison fibrinopeptide A (FPA), as a marker of an activated coagulation, as well as platelet factor 4 (PF4), and -thromboglobulin (-TG), as markers of platelet activation, were determined. In all patients in whom pulmonary embolism was confirmed by perfusion lung scan and in 15 of 16 patients in whom deep vein thrombosis was confirmed by phlebography, TAT exceeded the upper limit of normal (3.0 ng/ml). FPA was increased in 71% of the pulmonary embolism patients, PF 4 in 53%, and -TG in 59%. The data for the patients with deep vein thrombosis were comparable. PF 4 and -TG were increased in more than 25% of the normal controls, FPA in 17%, and TAT in 9%.TAT is very sensitive in detecting an activation of the coagulation system in patients with suspected thromboembolic events. The test, however, is not specific for thrombembolism; it only indicates an activation of the coagulation system. Acute pulmonary embolism or deep vein thrombosis would appear to be unlikely if TAT is normal. The measurement of TAT is easier and less susceptible to disturbances than that of FPA, PF4, and -TG.

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Abkürzungen FPA Fibrinopeptid A - LE Lungenembolie - PF 4 Plättchenfaktor 4 - TAT Thrombin-Antithrombin III-Komplex - -TG -Thromboglobulin (beta-Thromboglobulin) - VT tiefe Venenthrombose     

Relationship between hemostatic markers and platelet indices in patients with aortic aneurysm

The purpose of this study was to investigate whether platelet indices [platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR) and platelet distribution width (PDW)] could serve as diagnostic tools to evaluate the potential significance of platelet heterogeneity on thrombus formation in patients with aortic aneurysm (AA). Blood samples were obtained from 54 patients with AA (mean age 73 years; 40 males and 14 females), and from 120 age-matched controls (AC; mean age 74 years; 61 males and 59 females). Blood platelet indices were measured using an automated counter for all AC (n = 120) and AA (n = 54). Plasma thrombin-antithrombin III complex (TAT), alpha(2)-plasmin inhibitor-plasmin complex (PIC), D-dimer, von Willebrand factor antigen (vWF:Ag) and interleukin-6 (IL-6) were also measured in part of AC and AA. In AA patients, TAT, PIC, D-dimer, vWF:Ag and IL-6 levels were significantly (p < or =0.0005) higher than in AC. In the patients, TAT was significantly inversely correlated with platelet count (rho = -0.302, p = 0.038, n = 48), and significantly positively correlated with MPV (rho = 0.329, p = 0.0373, n = 48), P-LCR (rho = 0.361, p = 0.0134, n = 48) and PDW (rho = 0.315, p = 0.0466, n = 48). PIC was negatively correlated with platelet count and inversely correlated with MPV, P-LCR and PDW. vWF:Ag was not correlated with platelet count, and inversely correlated with MPV, P-LCR and PDW in the patients. IL-6 was positively correlated with platelet count, and significantly inversely correlated with MPV, P-LCR and PDW in the patients. In AC, vWF:Ag was inversely correlated with platelet count and significantly positively correlated with MPV, P-LCR and PDW. However, PIC, TAT and IL-6 were not correlated with platelet indices in AC. D-dimer was not at all correlated with platelet indices both in AA and AC. In conclusion, the correlation between platelet indices and plasma hemostatic factor levels, e.g. TAT, PIC, D-dimer, vWF:Ag and IL-6, will be important factors for the understanding of platelet heterogeneity in patients with AA.     

Novel approach for the prevention of contrast nephropathy

ObjectiveTo date, there is no effective treatment of contrast medium (CM)-induced nephropathy. Multiple studies documented a protective role of hydration and N-acetylcystein (NAC) as prophylactic agents against CM-induced nephropathy in a high-risk population. In the present study, we investigated a new antioxidant agent, caffeic acid phenethyl ester (CAPE), and compare with NAC against contrast nephropathy.MethodsForty-two adult male rats were divided into six experimental groups, which were control, injected with intravenous (i.v.) CM, injected with i.p. CAPE, injected with i.p. NAC, injected with i.v. CM pretreated with i.p. CAPE, injected with i.v. CM pretreated with i.p. NAC. CAPE and NAC were given daily throughout the study. All rats were deprived of water for 24 h at the third day of the study and then contrast medium was administered to CM, CAPECM and NACCM groups. The rats were sacrificed at the fifth day. Oxidant–antioxidant status was determined in renal tissues. The severity of injury was scored with a light microscope in renal tissue. Plasma creatinine levels were measured.ResultsRenal injury scores were higher in CAPECM and NACCM groups than in control, CAPE and NAC groups, but lower than the CM group. Likewise, creatinine levels of CAPECM and NACCM groups were higher than the control groups but they were significantly lower than the level of the CM group. Creatinine levels of the NACCM group were significantly higher than the CAPECM group. Malondialdehyde levels were significantly lower in CAPECM and NACCM groups than the CM group.ConclusionCAPE might protect renal structure and functions as well as NAC against CM injury.     

IgE-mediated adverse reactivity to a radiographic contrast medium.

In a patient with a previous history of a serious reaction after intravenous injection of the cholangiographic agent ioglycamic acid (Bilivistan), intravenous cholangiography appeared to be necessary. Therefore intradermal tests were performed in the patient and four controls with three radiographic contrast media closely related in chemical structure. In addition a Prausnitz-Kustner test with heated and unheated patient serum was performed. These tests demonstrated the presence in this patient of selective immediate-type reactivity to ioglycamic acid which was probably IgE mediated. Intravenous cholangiography with iodipamide seemed justified and resulted in no adverse reactions. Although this case may be exceptional, the results suggest that intradermal skin tests at proper concentrations may be useful in choosing the administration of radiographic contrast medium to patients with a history of prior adverse reactions.     

Veränderungen des Kallikrein-Kinin-und des Komplement-Systems bei Angiographien mit nicht-ionischen Kontrastmitteln

Summary To examine alterations of the kallikrein-kinin system and of the complement due to the bolus injection of newer non-ionic contrast agents, venous blood samples were taken before and 3 min after angiography. There were no adverse contrast reactions clinically evident. Prekallikrein, kallikrein inhibition, -factor XIIa inhibition, C1-esterase inhibitor, C1q, C3, ATIII, HMW-kininogen, fibrinogen and faktor XII were determined.Bolus injection of the contrast medium caused an activation of the kallikrein-kinin system (p<0.05) with reduction of prekallikrein, kallikrein-inhibition, -factor XIIa inhibition and C1-esterase inhibitor. The levels of C1q and C3 were also decreased (p<0.05) indicating an activation of the complement.Our results demonstrate, that angiography causes a significant activation of the kallikrein-kinin as well as of the complement system in spite of the use of newer non-ionic contrast agents.

     

Carbon dioxide contrast medium for endovascular treatment of ilio-femoral occlusive disease

OBJECTIVES:Compare the use of carbon dioxide contrast medium with iodine contrast medium for the endovascular treatment of ilio-femoral occlusive disease in patients without contraindications to iodine.RESULTS:No conversions to open surgery and no contrast media related complications were noted in either group. A post-operative femoral pulse was present in 88.9% of the iodine group and 80% of the carbon dioxide group. No differences in procedure length, endovascular material cost or renal function variation were noted between the groups. Four patients in the carbon dioxide group required iodine supplementation to complete the procedure. Contrast media expenses were reduced in the carbon dioxide group. Regarding angiographic image quality, 82% of the carbon dioxide images were graded as either good or fair by observers.CONCLUSIONS:The use of carbon dioxide contrast medium is a good option for ilio-femoral angioplasty in patients without contraindications to iodine and is not characterized by differences in endovascular material costs, procedure duration and surgical outcomes. In addition, carbon dioxide has lower contrast expenses compared with iodine.     

Effects of 5-thioglucose on feeding and glycemia in the hamster

Adult male hamsters (Mesocricetus auratus) did not increase their food consumption in a 5 hr feeding test when injected with doses of 5-thioglucose (5-TG) ranging up to 500 mg/kg, although insulin (50 U/kg) did produce hyperphagia. However, 5-TG did produce significant increases in both plasma glucose and plasma free fatty acids. Thus the hamster's failure to eat in response to 5-TG administration cannot be ascribed to a simple failure to detect the metabolic consequences of 5-TG. Hypotheses are proposed which may account not only for the hamster's failure to eat in response to 5-TG, but also for other well-established peculiarities in the feeding behavior of hamsters.     

Novel ultrasound contrast agent based on microbubbles generated from surfactant mixtures of Span 60 and polyoxyethylene 40 stearate

In this study, novel perfluorocarbon-filled microbubbles as ultrasound contrast agent were fabricated using ultrasonication of a surfactant mixture of sorbitan monostearate (Span 60) and polyoxyethylene 40 stearate (PEG40S) in aqueous media. The microbubbles generated from a 1:9 mixture of PEG40S/Span 60 exhibited an average diameter of 2.08 ± 1.27 μm. More than 99% of the microbubbles had a mean particle diameter less than 8 μm, indicating that they were appropriately sized for intravenous administration as ultrasound contrast agent. The stabilization mechanism of the microbubbles was investigated by the Langmuir–Blodgett technique including the measurements of surface pressure–area (π–A) isotherms and compression–decompression cycles with a two-dimensional monolayer of Span 60 and PEG40S. The dependence on molar fraction of PEG40S in π–A isotherms of mixed monolayers provided a strong evidence of interactions between the two microbubble-forming materials. It is suggested that the monolayer shell imparts good stability to the microbubbles by three means: (1) a low surface tension monolayer hinders dissolution through the reduction of surface tension, which introduces a mechanical surface pressure that counters the Laplace pressure; (2) the presence of a monolayer shell imparts a significant barrier to gas escaping from the core into the aqueous medium; and (3) encapsulation elasticity stabilizes microbubbles against diffusion-driven dissolution and explains the long shelf-life of microbubble contrast agent. The preliminary in vivo ultrasound imaging study showed that such stabilized microbubbles demonstrated excellent enhancement under grey-scale pulse inversion harmonic imaging and power Doppler imaging.     

Calcium content mediated hemostasis of calcium-modified oxidized microporous starch

Abstract

Blood coagulates are closely related to calcium ions (coagulation factor IV), and calcium-doped biomaterials have been reported to be effective in hemostasis. However, the effects exerted by calcium on hemostatic agents have not been previously investigated. The aims of this work were to develop calcium-modified oxidized microporous starch (CaOMS) with controllable calcium contents and to explore the relationship between calcium content and hemostatic effects. The results showed that low calcium content promoted coagulation, while high calcium content inhibited coagulation. CaOMS3 with 2.2 mg/g calcium content was optimal because of its excellent water absorption performance that enhanced physical coagulation, the rapid initiation of coagulation cascade reactions, and the enhanced chemical coagulation by RBC aggregation and platelet activation. The synergistic effects of chemical activation and physical absorption endowed CaOMS with the potential to control internal organ bleeding. These results suggested that CaOMS may be a promising hemostatic agent with wide spread applications.     

Diffusion of ionic and non-ionic contrast agents in articular cartilage with increased cross-linking—Contribution of steric and electrostatic effects

ObjectiveTo investigate the effect of threose-induced collagen cross-linking on diffusion of ionic and non-ionic contrast agents in articular cartilage.DesignOsteochondral plugs (Ø = 6 mm) were prepared from bovine patellae and divided into two groups according to the contrast agent to be used in contrast enhanced computed tomography (CECT) imaging: (I) anionic ioxaglate and (II) non-ionic iodixanol. The groups I and II contained 7 and 6 sample pairs, respectively. One of the paired samples served as a reference while the other was treated with threose to induce collagen cross-linking. The equilibrium partitioning of the contrast agents was imaged after 24 h of immersion. Fixed charge density (FCD), water content, contents of proteoglycans, total collagen, hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP) and pentosidine (Pent) cross-links were determined as a reference.ResultsThe equilibrium partitioning of ioxaglate (group I) was significantly (p = 0.018) lower (?23.4%) in threose-treated than control samples while the equilibrium partitioning of iodixanol (group II) was unaffected by the threose-treatment. FCD in the middle and deep zones of the cartilage (p < 0.05) and contents of Pent and LP (p = 0.001) increased significantly due to the treatment. However, the proteoglycan concentration was not systematically altered after the treatment. Water content was significantly (?3.5%, p = 0.007) lower after the treatment.ConclusionsSince non-ionic iodixanol showed no changes in partition after cross-linking, in contrast to anionic ioxaglate, we conclude that the cross-linking induced changes in charge distribution have greater effect on diffusion compared to the cross-linking induced changes in steric hindrance.     

Heliox-driven β2-agonists nebulization for children and adults with acute asthma: a systematic review with meta-analysis

BackgroundThe effect of heliox as a nebulizer β₂-agonist driving gas in acute asthma remains controversial.ObjectiveTo perform a systematic review with a meta-analysis of randomized trials designed to evaluate the efficacy of heliox versus oxygen in driving β₂-agonist nebulization in patients with acute asthma.MethodsA search was conducted of all randomized controlled trials published before August 2013. Primary outcomes were change in spirometric measurements and severity composite score (pediatric studies); secondary outcomes were hospitalizations and serious adverse effects.ResultsEleven trials from 10 studies (697 participants) met the inclusion criteria (7 included adults and 3 included children). The mean duration of heliox therapy was 120 minutes and the most common helium–oxygen mixture used was 70:30. Patients receiving heliox presented a statistically significant difference for mean percentage of change in peak expiratory flow (17.2%; 95% confidence interval 5.2–29.2, P = .005). Post hoc subgroup analysis showed that patients with severe and very severe asthma showed a significant improvement in peak expiratory flow compared with those with mild to moderate acute asthma. Heliox-driven nebulization also produced significant decreases in the risk of hospitalizations (odds ratio 0.49, 95% confidence interval 0.31–0.79, P = .003) and severity of exacerbations (pediatric studies; standard mean difference −0.74, 95%% confidence interval −1.45 to −0.03, P = .04). There were no group differences for serious adverse effects.ConclusionThis review suggests that heliox benefits in airflow limitation and hospital admissions could be considered clinically significant. Data support the use of heliox as a nebulizing β₂-agonist driving gas in the routine care of patients with acute asthma.     

Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug

Abstract

Context: β-d-Mannuronic acid (M2000) has shown its therapeutic effects with the greatest tolerability and efficacy in various experimental models such as experimental autoimmune encephalomyelitis (EAE), adjuvant induced arthritis (AIA), nephrotic syndrome, and acute glomerulonephritis. Despite pharmacological effects of β-D-mannuronic acid, there have been no systematic toxicological studies on its safety so far.

Objective: The study was designed to determine the acute and subchronic toxicity of β-D-mannuronic acid, an anti-inflammatory agent, in healthy male NMRI mice and Wistar rats, respectively.

Materials and methods: For the acute toxicity study, the animals received orally five different single doses of β-D-mannuronic acid and were kept under observation for 14?d. In the subchronic study, 24 Wistar male rats were divided into four groups and were treated orally (gavage) once daily with test substance preparation at dose levels of 0, 50, 250, and 1250?mg/kg body weight for at least 63 consecutive days (9 weeks). Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histopathological determinations were monitored during the study.

Results: The results of acute toxicity indicated that the LD₅₀ of β-D-mannuronic acid is 4.6?g/kg. We found no mortality and no abnormality in clinical signs, body weight, relative organ weights, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats.

Conclusions: Our results suggest that β-D-mannuronic acid is relatively safe when administered orally in animals.     

Melatonin has favorable preventive effects on experimental chronic pancreatitis rat model

Background/aim Currently, there is not any specific treatment for chronic pancreatitis (CP). It was aimed to investigate the effects of melatonin administration on endoplasmic reticulum (ER) stress, oxidative stress, fibrosis, biochemical and histopathological parameters, and Abcc2,Abcc5, and Abcg2 gene levels in an experimental rat CP model.Materials and methods Forty rats were randomized into five groups: Sham, CP, CP+25 mg/kg melatonin, CP+50 mg/kg melatonin, and CP+placebo. In all rats, except the sham group, a model of chronic pancreatitis was accomplished with intraperitoneal caerulein administration. In treatment groups, melatonin was used as a therapeutic agent. Serum TGF-β, TNF-α, MDA and GPx levels were studied. Pancreatic tissues were evaluated histopathologically. The expression levels of αSma,IR1α,Perk,Abcc2,Abcc5, and Abcg2 genes were measured with the qRT-PCR.Results Biochemical results of the melatonin groups exhibited favorable changes compared to the CP and placebo groups. α Sma,IR1α,Perk expression levels were significantly lower in the melatonin groups. The expression levels of Abcc2, Abcc5, and Abcg2 were significantly higher in the CP group compared to the sham group, and these gene levels were significantly lower in the melatonin groups compared to the CP group (p < 0.01, p < 0.05, p < 0.05, respectively).Conclusion In light of these favorable positive results, melatonin may be a useful preventive agent in the course of CP.