3-甲基喹噁啉-2-羧酸的制备及其细胞毒性

通过贝鲁特反应和还原、脱羧反应在体外合成制备3-甲基喹噁啉-2-羧酸,并进行理化鉴定和抗菌活性测试;通过MTT方法研究3-甲基喹噁啉-2-羧酸对多种细胞的生长抑制作用,利用单细胞电泳研究其对细胞DNA的损伤作用,利用流式细胞术研究其对细胞周期的改变。结果显示,体外成功合成制备出3-甲基喹噁啉-2-羧酸,而3-甲基喹噁啉-2-羧酸几乎没有抗菌效果,对多种细胞的生长抑制作用较弱,在剂量检测范围内细胞抑制率不到30%,但在一定剂量下能导致细胞DNA损伤,主要表现为尾长和尾部DNA含量显著升高;并且3-甲基喹噁啉-2-羧酸也能改变Chang细胞的细胞周期,表现为S期阻滞。结果表明,3-甲基喹噁啉-2-羧酸具有一定的细胞毒性。     

兽用喹噁啉类遗传毒性研究进展

综述了卡巴氧、喹乙醇、乙酰甲喹、喹烯酮、喹赛多等兽用喹噁啉类药物遗传毒性的研究进展,为此类药物在临床上的合理应用及毒性机制的深入研究提供参考.而此类药物主要代谢物的遗传毒性检测、代谢过程中自由基的产生、DNA修复酶活性变化、线粒体损伤程度等方面的研究,将有助于全面深入地揭示该类化合物的遗传毒性.     

兽用喹噁啉类药物毒理学机制的研究进展

<正>喹噁啉衍生物(quinoxalines)是一类重要的苯并吡嗪类杂环化合物,喹噁啉环上的2个N原子氧化形成的喹噁啉-1,4-二-N-氧化物(quinoxaline 1,4-di-N-oxides,qdNOs)具有多种生物学活性,包括抗细菌和抗念珠菌活性、促生长活性、抗虫活性和抗肿瘤活性等[1],在医药和农业中有着重要的应用价值和前景。含QdNO结构的动物用喹噁啉类兽药     

亚中毒剂量“喹胺醇”对大鼠组织形态学和饲料消耗盟影响

喹胺醇（Kuianchun）是一种新型药物饲料添加剂，其母体结构为喹噁啉-1，4-二氧化物，和喹烯酮、喹赛多等一样均属结构创新类药物，由中国农业科学院兰州畜牧与兽医研究所研制而成。前期研究结果表明，其抗菌促生长作用优于喹乙醇等，且毒性作用较小，合理使用后其在畜产品中的残留量很小。     

薄层色谱和液相色谱法鉴别中兽药散剂中掺加的磺胺喹噁啉钠

对磺胺喹噁啉钠采用硅胶GF254板为固定相,以正丁醇-浓氨水(15∶3)为展开剂,用薄层色谱鉴别中兽药散剂中磺胺喹噁啉钠分离较好,斑点显色清晰且无干扰,可用于中药散剂中非法添加物磺胺喹噁啉钠的快速筛选。采用C18柱为固定相,以甲醇-乙腈-水-冰乙酸(2∶2∶9∶0.2)为流动相,紫外检测波长为270 nm。液相色谱鉴别中药散剂中非法添加磺胺喹噁啉钠分离良好,无干扰峰,可用于中兽药散剂中非法添加物磺胺喹噁啉钠的鉴别。     

氟喹诺酮类药物粉剂中非法添加四种喹噁啉类药物的UPLC检测方法研究

建立了超高效液相色谱法测定氟喹诺酮类药物粉剂中非法添加喹乙醇、乙酰甲喹、卡巴氧及喹烯酮的方法。采用purospher RP-18色谱柱(2.1 mm×100 mm,粒径2.0μm)分离四种喹噁啉类药物,以磷酸溶液和甲醇-乙腈(7.5∶7.0)为流动相进行梯度洗脱,流速0.3 m L/min,二极管阵列检测器检测,采集波长范围为200~400 nm,分辨率为1.2 nm,记录光谱图和365 nm波长处的色谱图。结果显示,四种喹噁啉类药物的浓度在0.2~100μg/m L范围内的线性良好,相关系数r均为0.9999,回收率在98.0%~100.2%范围内,RSD在0.27%~0.89%之间,检测限200 mg/kg。本方法快速、准确,可用于氟喹诺酮类粉剂中非法添加喹噁啉类药物的定性和定量检测。     

亚中毒剂量"喹胺醇"对大鼠组织形态学和饲料消耗的影响

喹胺醇(Kuianchun)是一种新型药物饲料添加剂,其母体结构为喹噁啉-1,4-二氧化物,和喹烯酮、喹赛多等一样均属结构创新类药物,由中国农业科学院兰州畜牧与兽医研究所研制而成.     

2-乙酰基-3-甲基喹噁啉-1,4-二氧化物的合成工艺研究

研究了2-乙酰基-3-甲基喹噁啉-1,4-二氧化物的合成工艺.以邻硝基苯胺为起始原料,经过氧化反应和Beirut反应,以86%的总收率制得产物2-乙酰基-3-甲基喹噁啉-1,4-二氧化物.反应条件温和,操作简单,收率高,具有工业应用价值.     

仔猪乙酰甲喹中毒的诊治

乙酰甲喹又称痢菌净,是一种较新型的合成抗菌药,属于喹噁啉类药物。广谱抗菌,抗菌机理为抑制菌体的脱氧核糖核酸(DNA)的合成,其对多数细菌、密螺旋体有较强的抑制作用。临床上对猪细菌性肠炎、仔猪副伤寒、猪痢疾等病有疗效。内服或肌注均易吸收,长期或大剂量应用易引起中毒。     

喹噁啉类药物抗肿瘤与抗菌活性的研究进展

喹噁啉类药物是畜牧生产中大量使用的抗菌促生长添加剂,同时在医药领域也进行着大量的研究,在国际上得到广泛的重视。主要介绍了目前国内外在喹噁啉类药物在抗肿瘤和抗菌生物活性方面作用的研究进展,并且探讨了其作用的机理。     

Influence of aging on adrenal responsiveness in a population of eleven healthy beagles

The present study aimed at investigating the effects of aging on the adrenal cortex response of cortisol and aldosterone in dogs.A population of healthy adult Beagles was evaluated twice at a five-year interval. At each evaluation, plasma basal cortisol and aldosterone, cortisol and aldosterone following ACTH-stimulation, sodium, and potassium concentrations and arterial blood pressure were measured. We observed significantly (p < 0.05) greater sodium, urea and creatinine concentrations with aging. Nevertheless urea and creatinine remained within our laboratory reference ranges. This study showed a highly significant age-related elevation of basal cortisol (p < 0.01). Inversely, both aldosterone following ACTH-stimulation levels and difference between aldosterone following ACTH-stimulation and basal aldosterone values plummeted significantly (p < 0.01) with aging. In conclusion, the evaluation of the adrenal cortex function in dogs should take in consideration the age of the individuals.     

Hyponatremia and hyperkalemia associated with peritoneal effusion in four cats

Four cats with considerable peritoneal effusion and corresponding hyponatremia and hyperkalemia were evaluated. The Na:K ratio in all cats was < 25, which is suggestive of adrenal insufficiency. An ACTH stimulation test was performed on 3 cats for evaluation of adrenal gland function. Serum cortisol and aldosterone concentrations did not support a diagnosis of adrenal gland insufficiency. In 1 cat, histologic evaluation of the adrenal glands at necropsy also failed to support a diagnosis of hypoadrenocorticism. On the basis of these findings, and because hyponatremia and hyperkalemia could not be readily explained by another cause, the electrolyte abnormalities were presumed to be secondary to peritoneal effusion.     

喹乙醇在鸡体内的毒物动力学及其生化毒性和病理学研究 Ⅱ.喹乙醇对鸡的生化毒性和病理学研究

本文报道了喹乙醇多剂量给药时对ＡＡ鸡的生化毒性和病理学研究。４２只ＡＡ鸡随机分成７组,按喹乙醇５００ｍｇ／ｋｇ饲料连续饲喂７ｄ,测定生化指标并作病理学检查。结果表明,血浆醛固酮显著下降、血清Ｎａ＋下降而血清Ｋ＋显著上升、Ｎａ＋／Ｋ＋比显著下降、肝微粒体蛋白含量呈起伏变化、细胞色素Ｐ－４５０含量减少、血浆肌酐和血清尿酸均显著上升（Ｐ＜０．０５或Ｐ＜０．０１）,肝、肾和肾上腺组织结构均受损害。本研究证实,中毒剂量的喹乙醇对鸡的肾上腺皮质功能、肝微粒体酶系统及肾功能均产生抑制性损害。病理学变化与生化指标的变化相一致。     

Idiopathic hyperaldosteronism in a dog

Idiopathic hyperaldosteronism was diagnosed in an 8-year-old castrated male Yorkshire Terrier, based on increased concentration of plasma aldosterone, hypertension, hypernatremia, decreased natriuresis, hypokalemia, and hyperkaluria. Unilateral adrenalectomy was performed after visualization of a nodule on the right adrenal gland. Hyperplasia of the zona glomerulosa and increased postoperative aldosterone concentrations supported the diagnosis of idiopathic hyperaldosteronism.     

Primary hyperaldosteronism in the cat: a series of 13 cases

Thirteen cases of feline primary hyperaldosteronism were diagnosed based on clinical signs, serum biochemistry, plasma aldosterone concentration, adrenal imaging and histopathology of adrenal tissue. Two cases presented with blindness caused by systemic hypertension, whilst the remaining 11 cases showed weakness resulting from hypokalaemic polymyopathy. Elevated concentrations of plasma aldosterone and adrenocortical neoplasia were documented in all cases. Seven cases had adrenal adenomas (unilateral in five and bilateral in two) and six had unilateral adrenal carcinomas. Three cases underwent medical treatment only with amlodipine, spironolactone and potassium gluconate; two cases survived for 304 and 984 days until they were euthanased because of chronic renal failure, whilst the third case was euthanased at 50 days following failure of the owner to medicate the cat. Ten cases underwent surgical adrenalectomy following a successful stabilisation period on medical management. Five cases remain alive at the time of writing with follow-up periods of between 240 and 1803 days. Three cases were euthanased during or immediately following surgery because of surgical-induced haemorrhage. One cat was euthanased 14 days after surgery because of generalised sepsis, whilst the remaining cat was euthanased 1045 days after surgery because of anorexia and the development of a cranial abdominal mass. It is recommended that primary hyperaldosteronism should be considered as a differential diagnosis in middle-aged and older cats with hypokalaemic polymyopathy and/or systemic hypertension and should no longer be considered a rare condition.     

Primary hyperaldosteronism in two cats.

A condition of primary hyperaldosteronism resulting from an adrenal tumor in two cats is presented and was characterized by hypertension, hypokalemia, inappropriate kaliuresis, low normal plasma renin activity, and markedly increased serum aldosterone concentration. One of the two cats underwent a laparotomy, and in this case hypertension and hypokalemia resolved following the removal of an adrenal tumor.     

The effects of 10% hypertonic saline, 0.9% saline and hydroxy ethyl starch infusions on hydro-electrolyte status and adrenal function in healthy conscious dogs

The purpose of this study was to investigate the influence of different saline and colloid solutions on adrenal steroid secretion in dogs. Six healthy male Beagles underwent three infusion cycles: 10 min infusion of 30 ml/kg of NaCl 0.9%, 5 ml/kg of hydroxy ethyl starch, or 5 ml/kg of NaCl 10%. Plasma osmolality, hematocrit, total solids, cortisol and aldosterone levels were measured at 0, 5, 15, 30, 60, 120, 180 and 240 min after beginning infusion. Plasma ACTH levels were measured at 0, 15 and 240 min. An identical timing of sampling was applied during a control session omitting the fluid infusion. Osmolality, sodium, chloride and cortisol levels were found to be significantly higher with hypertonic saline solute compared to control. All fluid infusions lead to lowered plasma potassium, hematocrit, total solids and aldosterone values. ACTH concentrations did not show significant changes with any of the infusion cycles. The increase in cortisol levels suggests that hypertonic saline infusion could be interesting in critical care resuscitation, particularly in patients who are suffering from relative adrenal insufficiency.     

Blood supply of the ovine adrenal gland and its relevance in adrenal autotransplantation

SUMMARY The arterial supply and venous drainage of 62 left and 5 right ovine adrenal glands is described, and the contribution of individual arteries to successful adrenal gland autotransplantation was evaluated. Arterial flow was measured by direct collection from the draining adrenal vein. Assessment of function of the transplanted adrenal gland was made from survival of the sheep and by the cortisol response to infusion of ACTH and the aldosterone secretory response to infusion of angiotensin II or potassium. For the left adrenal, the principal arterial supply was from the renal artery in 21 (34%), a lumbar artery in 32 (52%), and the anterior mesenteric artery in 3. The total blood flow was 5.0 ± SEM 0.4 mL/min, the flow from the renal branch 2.3 ± 0.3 mL/min, and the principal lumbar branch 2.6 ± 0.3 mL/min. Venous drainage from the left adrenal was via a major adrenal vein to the left renal vein, but additional tributaries to the renal vein were present in 26% . The arterial supply to the adrenal is regional and omission of a branch at transplantation could result in infarction of portion of the gland. By defining arterial supply and measuring blood flow, selection of the appropriate artery or multiple arteries can achieve an adrenal gland autotransplant survival of 90% .     

Functioning unilateral adrenocortical carcinoma in a dog

An 11-year-old, 24-kg, intact female Siberian husky dog in anestrus had a 2-month history of polyuria and polydipsia. The dog had signs of mineralocorticoid excess such as hypertension and hypokalemia refractory to potassium supplementation. Abdominal ultrasound revealed an irregular mass in the left adrenal gland. The ACTH stimulation test for aldosterone concentration did not reveal hyperaldosteronism. Unilateral adrenalectomy was performed and histopathology identified adrenal cortical carcinoma. All clinical signs of mineralocorticoid excess ceased after surgery.     

Practical approaches for evaluating adrenal toxicity in nonclinical safety assessment

The adrenal gland has characteristic morphological and biochemical features that render it particularly susceptible to the actions of xenobiotics. As is the case with other endocrine organs, the adrenal gland is under the control of upstream organs (hypothalamic-pituitary system) in vivo, often making it difficult to elucidate the mode of toxicity of a test article. It is very important, especially for pharmaceuticals, to determine whether a test article-related change is caused by a direct effect or other associated factors. In addition, antemortem data, including clinical signs, body weight, food consumption and clinical pathology, and postmortem data, including gross pathology, organ weight and histopathologic examination of the adrenal glands and other related organs, should be carefully monitored and evaluated. During evaluation, the following should also be taken into account: (1) species, sex and age of animals used, (2) metabolic activation by a cytochrome P450 enzyme(s) and (3) physicochemical properties and the metabolic pathway of the test article. In this review, we describe the following crucial points for toxicologic pathologists to consider when evaluating adrenal toxicity: functional anatomy, blood supply, hormone production in each compartment, steroid biosynthesis, potential medulla-cortex interaction, and species and gender differences in anatomical features and other features of the adrenal gland which could affect vulnerability to toxic effects. Finally practical approaches for evaluating adrenal toxicity in nonclinical safety studies are discussed.