泮托拉唑联合托烷司琼防治化疗所致消化道反应的临床观察

目的:观察泮托拉唑与托烷司琼+地塞米松联用治疗肿瘤化疗所致消化道反应的疗效。方法:将96例化疗所致难治性呕吐的患者随机分为2组,在下一周期化疗中泮托拉唑组给予泮托拉唑+托烷司琼+地塞米松,对照组给予托烷司琼+地塞米松。结果:泮托拉唑组在预防食欲不振,抑制恶心、呕吐等方面明显优于对照组(P均<0.05)。结论:泮托拉唑联合托烷司琼防治化疗药物所致消化道反应疗效较好,值得临床推广应用。     

盐酸帕洛诺司琼预防乳腺癌术后化疗所致恶心呕吐的疗效观察及护理

目的观察盐酸帕洛诺司琼在乳腺癌化疗中预防恶心呕吐的疗效。方法 64例乳腺癌化疗患者随机分为盐酸帕洛诺司琼治疗组和盐酸托烷司琼治疗组,两组患者均为术后首次接受FEC方案化疗,观察24h、48h、96h内恶心呕吐发生的情况并作比较。结果在化疗后24h、48h、96h内盐酸帕洛诺司琼对预防化疗所致恶心呕吐的有效率分别为93.75%、87.5%、87.5%,盐酸托烷司琼对预防化疗所致恶心呕吐的有效率分别为75.0%、65.63%、59.38%,两组差异均有统计学意义(P<0.05),盐酸帕洛诺司琼在不同时段的疗效均优于盐酸托烷司琼。结论盐酸帕洛诺司琼能有效预防化疗所致恶心呕吐,可作为乳腺癌化疗中预防治疗恶心呕吐的首选药物之一,值得临床推广。     

托烷司琼联合地塞米松及穴位贴敷预防乳腺癌化疗中恶心呕吐的疗效观察

目的 观察托烷司琼联合地塞米松及穴位贴敷预防乳腺癌化疗恶心呕吐的疗效.方法 85例乳腺癌化疗患者随机分为干预组46例及对照组39例,干预组在化疗前给予静脉滴注托烷司琼和地塞米松,且给予穴位贴敷治疗,对照组化疗前只给予托烷司琼.观察2组临床疗效.结果 治疗后干预组有效率为86.96%高于对照组的69.23%,差异有统计学意义(P<0.05).结论 对乳腺癌化疗后给予托烷司琼联合地塞米松及穴位贴敷治疗可大大减轻患者的恶心及呕吐.     

泮托拉唑联合托烷司琼预防化疗不良反应疗效

目的：观察泮托拉唑与托烷司琼＋地塞米松联合治疗肿瘤患者化疗所致消化道不良反应的疗效和不良反应。方法：将80例化疗患者随机分为P、T两组,P组为治疗组,给予泮托拉唑＋托烷司琼＋地塞米松;T组为对照组,给于托烷司琼＋地塞米松,比较两组的临床效果与药物不良反应。结果：治疗组在预防食欲不振、抑制恶心、呕吐等方面明显优于对照组（P〈0．05）;两组头晕、腹痛、便秘、乏力、颜面潮红、失眠等不良反应发生率相仿（P〉0．05）。结论：泮托拉唑联合托烷司琼预防化疗所致消化道反应疗效好,值得临床推广。     

盐酸帕洛诺司琼预防含顺铂方案化疗恶心、呕吐的临床观察

目的观察盐酸帕洛诺司琼预防含顺铂方案化疗中所致恶心、呕吐的疗效和安全性。方法选择含顺铂方案化疗的肿瘤患者60例,随机分为观察组和对照组;试验组为盐酸帕洛诺司琼注射液;对照组为盐酸托烷司琼注射液。对化疗及化疗后1~4d的恶心、呕吐程度、控制效果及不良反应进行评价。结果盐酸帕洛诺司琼治和盐酸托烷司琼治疗后急性恶心、呕吐发生程度有差异(P<0.05);延迟性呕吐两组差异有统计学意义(P<0.05);延迟性恶心两组差异无统计学意义(P>0.05)。结论盐酸帕洛诺司琼在防治含铂方案化疗所引起的急性恶心、急性及延迟性呕吐的疗效优于盐酸托烷司琼,且使用方便、安全性好,值得临床推广。     

含服生姜片联合托烷司琼预防顺铂所致恶心呕吐的研究

目的：探讨含服生姜片联合托烷司琼预防顺铂所致的恶心呕吐的效果。方法将100例含顺铂标准化疗的患者随机分为观察组和对照组各50例,对照组使用托烷司琼静脉滴注预防恶心呕吐,观察组在对照组治疗的基础上联合采用生姜片含服,观察比较两组病人恶心呕吐情况。结果观察组化疗后恶心呕吐发生率显著低于对照组（P＜0．05）。结论含服生姜片联合托烷司琼能缓解顺铂化疗后引起的恶心呕吐,止吐效果显著。     

泮托拉唑联合托烷司琼、地塞米松治疗化疗所致的消化道反应

目的：观察泮托拉唑联合托烷司琼、地塞米松防治卡培他滨联合奥沙利铂（XELOX）方案所致消化道反应的疗效和不良反应。方法：将98例使用XELOX化疗方案的晚期胃癌肿瘤患者随机分为两组,干预组化疗期间给予托烷司琼、泮托拉唑和地塞米松,对照组化疗期间给予托烷司琼和地塞米松,比较两组的临床效果与药物不良反应。结果：干预组在预防肿瘤患者食欲不振、抑制恶心、呕吐等方面明显优于对照组（P〈0．01）,两组其他不良反应发生率无明显差异（P〉0．05）。结论：泮托拉唑联合托烷司琼、地塞米松防治XELOX方案化疗所致消化道反应疗效较好,值得临床应用。     

肿瘤患者化疗中托烷司琼与格拉司琼止吐作用的疗效观察

目的:采用托烷司琼和格拉司琼预防肿瘤化疗引起的恶心呕吐,并对其疗效进行观察.方法:将90例恶性肿瘤患者随机分为托烷司琼组和格拉司琼组,每组45例,两组患者均首次接受化疗,观察两组患者恶心、呕吐的程度及治疗效果.结果:托烷司琼组对预防恶性肿瘤化疗所致恶心、呕吐总有效率为75.5%,格拉司琼组总有效率为71.1%,两组疗效基本相似,P>0.05.结论:在肿瘤化疗中,托烷司琼与格拉司琼止吐作用的疗效基本相似,托烷司琼每日用药1次,更为方便.     

阿瑞匹坦和托烷司琼及柠檬皮片联合使用防治卵巢癌化疗患者恶心呕吐的效果分析

目的：探讨阿瑞匹坦联合柠檬皮片和托烷司琼防治卵巢癌化疗患者恶心呕吐的效果。方法：选择2021年6月—2023年6月收治的卵巢癌化疗患者110例,随机分为对照组和观察组,每组55例。对照组给予托烷司琼注射液联合柠檬皮片闻味治疗,观察组在对照组基础上口服阿瑞匹坦,比较两组的化疗相关性恶心、呕吐的预防效果及用药不良反应。结果：治疗后,观察组患者的恶心预防有效率、急性呕吐预防有效率和延迟性呕吐预防有效率均高于对照组,差异有统计学意义(P<0.05);两组用药不良反应发生率比较,差异无统计学意义(P>0.05)。结论：阿瑞匹坦、托烷司琼及柠檬皮片联合使用可提高卵巢癌患者化疗期间恶心呕吐预防效果,改善患者化疗耐受性,且不会加重止吐药的不良反应。     

托烷司琼联合健脾理气止呕中药预防乳腺癌术后化疗所致恶心呕吐疗效观察

目的 观察托烷司琼联合健脾理气止呕中药预防乳腺癌术后化疗所致的恶心、呕吐的疗效.方法 采用随机对照方法,将85例乳腺癌术后化疗患者随机分为两组,均接受两个周期 FAC方案(环磷酰胺、阿霉素、氟尿嘧啶)化疗,在化疗前,治疗组46例予盐酸托烷司琼加健脾理气止呕中药300ml分3次口服止吐,对照组39例单纯用托烷司琼注射液常规治疗.结果 治疗组与对照组有效率为 85.86%和 69.23%,两组比较差异有统计学意义 (P＜0.05).结论 托烷司琼联合健脾理气止呕中药可以较好的防治乳腺癌术后化疗药引起的恶心呕吐,方案安全、有效、易行.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Arsenic induced changes in growth development and apoptosis in neonatal and adult brain cells in vivo and in tissue culture

Arsenic at a nonlethal level in drinking water consumed over a period of time has been reported to produce chronic toxicity and various types of health problems ranging from skin cancer to disturbance in memory. Neurotoxic effects have been reported in clinical cases with chronic exposure to arsenic. Physiological detoxication of arsenic occurs partially through methylation. Arsenic and its methylated derivatives are distributed in different organs and systems. The present study examined the possible interference in the neuronal development and differentiation due to the exposure to arsenic during gestation. The experiments were carried out to examine short and long term effects of arsenic on brain explants and cells grown and maintained in tissue culture system. The effects of arsenic exposure showed changes in brain cell membrane function indicated by generation and release of reactive oxygen-nitrogen intermediates. On the morphological aspect the explants' growth was reduced, ground matrix was lost and neural networking was inhibited. Cells showed signs of apoptotic changes. Arsenic toxicity may induce damage to brain cells prior to more visible clinical conditions. The deleterious effects also pass from the maternal to fetal tissue across the transplacental barrier.     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85–100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.     

Circulating nucleic acids in plasma and serum: roles in diagnosis and prognosis in diabetes and cancer

The presence of DNA and RNA circulating in human plasma and serum is described. The possible sources of the DNA/RNA in blood, their ability to enter other cells and to express in the recipient cells are discussed and the relationship with metastases considered. The possible role(s) of the DNA/RNA in clinical diagnosis, in monitoring treatment and in prognosis are considered for diabetes and oncology.     

SalB stimulates neurogenesis and angiogenesis in vitro and in vivo

Aims： Previous studies suggested that Salvianolic acid B （SalB） has strong protective effect against cerebral ischemia. Recently, Sal B has been reported to enhance angiogenesis in vitro. Based on the information above, in this study we are interested in the effect of SalB on neurogenesis and angiogenesis. Methods：In vitro study, we used embryonic mouse （El6） primary cortical neural cultures. Neuron was recognized by anti-MAP2 with immunocytochemistry. Neurogenesis was tested with BrdU incorporation by ELSA method. SalB（ 10 -6 -10 -8M） or vehicle was added to the culture medium 24 hrs before BrdU addition. In vivo, middle cerebral artery occlusion （MCAO） rats were used as focal cerebral ischemia model.     

Metabolic interaction between imipramine and carbamazepine in vivo and in vitro in rats

Summary The pharmacokinetic consequences of the combination of carbamazepine with imipramine in male Wistar rats have been investigated. It was found that a 2-week treatment with the combination resulted in the increase of the concentrations of the parent compounds and a simultaneous decrease in their metabolites in blood plasma i.e. carbamazepine inhibited imipramine demethylation in the side chain while imipramine inhibited carbamazepine 10,11-epoxidation. The velocity of imipramine 2-hydroxylation and 10,11-epoxy-carbamazepine hydration did not seem to be changed by the combination. On the basis of studies in vitro it is concluded that the observed metabolic interaction between carbamazepine and imipramine is due to the competition of the drugs for the active centre of cytochrome P 450 and to a certain qualitative alteration of the enzyme by imipramine as can be deducted from the decrease of carbamazepine binding to the cytochrome. Send offprint requests to K. J. Netter     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85-100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.     

Pharmacokinetic and pharmacogenetic determinants and considerations in chemotherapy selection and dosing in infants

INTRODUCTION: There is a lack of high-quality data regarding optimal chemotherapy dosage regimens among infants. Dosing regimens for chemotherapy during the first year of life are commonly based on empiric recommendations extrapolated from older children; however, balancing efficacy and toxicity is critical as severe adverse drug reactions may lead to treatment failure or reduced adherence to needed medications. AREAS COVERED: This review describes pharmacokinetic and pharmacogenetic considerations when administering chemotherapeutic agents to infants. Examples of commonly used agents are provided with practical recommendations for dosing adjustments. EXPERT OPINION: Optimal chemotherapy for children and infants in particular has lagged behind the remarkable progress in cancer treatment and it is clear that far more basic and clinical research are needed with respect to the mechanistic basis of age-dependent differences in pharmacokinetic parameters. More recent studies which have combined pharmacokinetic data with clinical toxicity and outcome data have resulted in a number of more evidence-based guidelines at least for the initial chemotherapy dosing; however, at present, the dosing of chemotherapy drugs in neonates and infants remains largely empiric.     

Consistency in catecholamine and cortisol excretion in males and females

Data from a series of experiments performed on 24 female and 24 male subjects were used to evaluate the consistency in urinary catecholamine and cortisol excretion. Data were available from 8 laboratory situations of varying activity level and content, spaced at intervals of maximum 3 months. Correlational analyses showed that for cortisol, interindividual consistency was higher for measures obtained on the same day than for measures obtained on different days. Interindividual consistency was generally high in catecholamine and cortisol excretion during non-stressful situations in both sexes. During experimental stress, however, consistency was as high as during nonstress for males, while it was lower for females. Analysis of variance components confirmed these results and showed that in males variation due to interindividual differences was high during both baseline and experimental-stress situations, while in females it was high during baseline situations only. During experimental stress, variation for females was due primarily to interaction. It is suggested that the males showed a more generalized stress response over situations than the females.     

Penetration and action of edoxudine in vitro and in vivo

The penetration of 5-ethyl-2'-deoxyuridine (edoxudine, Aedurid) from gel base with and without the addition of urea and other adjuvant has been studied in an in vitro model using guinea pig skin. The formulation of 3% edoxudine gel with 5% urea showed the best results. In vivo experiments on hairless mice infected intracutaneously with herpes simplex virus type 1 also showed this formulation's good efficacy as compared to other formulations.