Anti-hyperalgesic effect of an ethanolic extract of propolis in mice and rats

Abdominal obesity, anxiety, and depression have been found to cluster in several studies. To further characterize these associations, the following study was performed. In a population of 51-year-old men (N = 284), measurements of obesity (body mass index [BMI]) and body fat distribution (waist to hip ratio [WHR] and sagittal trunk recumbent diameter [D]) were analyzed in relation to dexamethasone (0.5 mg) inhibition of cortisol secretion, measured as salivary cortisol. Symptoms of anxiety and depression were defined by a validated questionnaire. Furthermore, testosterone, insulin-like growth factor-I (IGF-I), insulin, glucose, and serum lipid levels were measured. Twenty-five men (8.8%) had symptoms of anxiety and depression. BMI, WHR, and D correlated negatively with testosterone, except for BMI in the anxio-depressive (ADP) group. IGF-I showed no significant relationship. Furthermore, fasting insulin and the insulin to glucose ratio correlated positively and high-density lipoprotein (HDL) cholesterol correlated negatively with BMI, WHR, and D in the total study population and in the subgroups. Total and low-density lipoprotein (LDL) cholesterol showed no significant relationships. Correlation coefficients tended to be higher in ADP men. Dexamethasone inhibition showed a negative significant relationship with BMI (rho = -.47, P = .025), WHR (borderline, rho = -.37, P = .086), and D (rho = -.43, P = .046) only in the ADP group. Comparing the ADP group versus the group without anxio-depression (ADO) and high or low BMI (P = .008), WHR (P = .026), and D (P = .012) showed blunted dexamethasone inhibition only in ADP men with high anthropometric measurements. These findings suggest there is a subgroup with elevated BMI, WHR, and D in whom a blunted dexamethasone response is found associated with traits of anxiety and depression, conditions characterized by such an abnormality. The reason for the association might be insufficient control of cortisol secretion, followed by visceral fat accumulation.     

放射性125I 粒子植入对裸鼠人乳腺癌细胞移植瘤的抗肿瘤作用

目的:探讨放射性125I 粒子植入对裸鼠人乳腺癌细胞种植瘤的抗肿瘤作用,阐明其抗肿瘤机制.方法:将120只人乳腺癌细胞MCF-7移植瘤模型的裸鼠,随机分为3组:放射性125I粒子植入组、空粒子植入组和无粒子植入组,每组40只,按照巴黎系统原则植入粒子.采用RT-PCR和Western blotting法检测肿瘤组织中Fas mRNA和蛋白的表达以及caspase-3和caspase-8酶的活性,流式细胞术检测细胞周期.结果:人乳腺癌细胞MCF-7放射性125I 植入组与空粒子组及无粒子植入组比较,肿瘤组织体积明显缩小(P<0.05),Fas mRNA、Fas蛋白、caspase-3及caspase-8表达均明显增高(P<0.05),其中caspase-3和caspase-8表达均大于0.6.流式细胞术显示,放射性125I粒子植入组G0/G1期细胞显著增多(P<0.05),而S期细胞明显降低(P<0.05).结论:放射性125I 粒子植入人乳腺癌肿瘤内可以杀伤肿瘤细胞,抑制肿瘤细胞生长周期,促进肿瘤细胞凋亡.     

In vivo effect of chemically induced fibrosarcoma on copper metabolism of liver in mice

The clinical and serological responses to therapy were evaluated for at least 1 year in 68 dogs with antibody titers positive for Ehrlichia canis. Treatments were of variable periods with primarily tetracycline hydorchloride and/or doxycycline. Sixteen dogs had initial titers of 1:20 and, at the end of the year, were asymptomatic, no longer receiving medication, and had negative serology. The average length of treatment with tetracycline HCl and/or doxycycline was 85 days (range, 14 to 360 days). Of 39 dogs with initial titers of 1:2,560 or greater, 1 died, 25 were asymptomatic, and 13 were lost to follow-up at the end of the study. The average length of treatment was 210 days (range, 21 to 630 days). Twenty-seven dogs were seropositive at > or = 1:2,560 when the sera was last tested. Thirteen dogs had initial titers of 1:80 to 1:1,280. Of these 13 dogs, 2 died, 2 were lost to follow-up, and 9 were asymptomatic and had titers ranging from negative to > or = 1:2,560 at the end of the study. The persistence of antibodies, prolonged subclinical phase, and delayed relapses despite long-term medication, suggest inadequate chemotherapeutic agents or may be natural features of latency of ehrlichiosis in dogs.     

Selective protective effect of an extract from Fumaria parviflora on paracetamol-induced hepatotoxicity

1. The hepatoprotective activity of an aqueous-methanolic extract of Fumaria parviflora was investigated against paracetamol- and CCI4-induced hepatic damage. 2. Paracetamol (1 g/kg; orally) produced 100% mortality in mice; pretreatment of animals with the plant extract (500 mg/kg; orally) reduced the death rate to 50%. 3. Pretreatment of rats with plant extract (500 mg/kg, orally twice daily for 2 days) prevented (P < 0.001) the paracetamol (640 mg/kg)-induced rise in serum enzymes alkaline phosphatase (ALP) and transaminases (GOT and GPT), whereas the same dose of the extract was unable to prevent (P > 0.05) the CCI4-induced rise in serum enzyme levels. 4. Posttreatment with 3 successive doses of the extract (500 mg/kg, 6 hourly) also restricted the paracetamol-induced hepatic damage. 5. The plant extract (500 mg/kg; orally) caused significant prolongation in pentobarbital (75 mg/ kg)-induced sleep as well as increased strychnine-induced lethality in mice (P < 0.05), suggestive of an inhibitory effect on microsomal drug metabolizing enzymes (MDME). 6. It is conceivable therefore, that Fumaria parviflora extract exhibits a selective protective effect against paracetamol-induced hepatotoxicity, probably mediated through MDME inhibition.     

Myocardial beta-adrenergic receptor signaling in vivo: insights from transgenic mice

Heart failure is a problem of increasing importance in cardiovascular medicine. An important characteristic of heart failure is reduced agonist-stimulated adenylyl cyclase activity (receptor desensitization) due to both diminished receptor number (receptor downregulation) and impaired receptor function (receptor uncoupling). These changes in the section-adrenergic receptor (section-AR) system may in part account for some of the abnormalities of contractile function in this disease. Myocardial contraction is closely regulated by G protein coupled beta-adrenergic receptors through the action of the second messenger cAMP. The beta-adrenergic receptors themselves are regulated by a set of specific kinases, termed the G-protein-coupled receptor kinases. The study of this complex system in vivo has recently been advanced by the development of transgenic and gene targeted ("knockout") mouse models. Combining transgenic technology with sophisticated physiological measurements of cardiac hemodynamics is an extremely powerful strategy to study the regulation of myocardial contractility in the normal and failing heart.     

The effect of intraperitoneal and intra-aortic chemotherapy for unresectable gastric cancer

Regional chemotherapy was given 16 unresectable gastric cancer patients. Two types of the chemotherapy, intraperitoneal (IP) and intraaortic (IA) administration, were carried out. The control group was comprised of 17 patients. The response of the chemotherapy for primary tumor was 36.4% in the IP group and 20% in the IA one. Among these patients, 2 of 11 in IP and 1 of 5 in IA were able to resect the primary tumor. The 50% survival time of IP, IA and control was 347, 227 and 78 days, respectively. One-year survival rates of IP, IA and control were 68%, 29% and 0%, respectively. IP showed a significantly longer survival rate than controls (p < 0.001). All but one patient was able to stay at home. Intraperitoneal chemotherapy showed both local and systemic effects in unresectable gastric cancer.     

Dietary lutein from marigold extract inhibits mammary tumor development in BALB/c mice

Even though lutein can stimulate immunity and decrease cancer growth, no systematic studies are available on the uptake of lutein in mice. We studied the uptake of lutein in 8-wk-old female BALB/c mice fed a diet containing 0, 0.05, 0.1, 0.2 or 0.4% lutein. Mice were killed on d 0, 3, 7, 14, 21 and 28 (n = 6/period), and blood, spleen and liver were collected. Food intake and body, liver and spleen weights did not differ among treatment groups. Lutein + zeaxanthin were not detectable in the plasma, liver and spleen of unsupplemented mice. Mice fed lutein showed very rapid lutein + zeaxanthin absorption. On d 3, concentrations of plasma lutein + zeaxanthin had rapidly increased (P < 0.05) in lutein-fed mice and no further increases were observed. Plasma lutein + zeaxanthin concentrations did not differ among lutein-fed mice by d 7 (2.58 +/- 0.2 micromol/L). Even though maximal uptake of plasma lutein + zeaxanthin was observed by d 3, uptake of lutein + zeaxanthin by the liver and especially by the spleen generally continued to increase (P < 0.05) through d 28 to reach concentrations of 0.11 +/- 0.001 (spleen) and 0.71 +/- 0. 0002 (liver) nmol/g. Therefore, dietary lutein is readily absorbed into the plasma and taken up by liver and spleen of mice. Plasma lutein + zeaxanthin concentrations were higher than in human studies; however, mice were fed lutein at a level several hundredfold greater than in humans. The liver is a major storage organ for lutein + zeaxanthin in mice. Uptake of lutein + zeaxanthin by the spleen suggests a role for lutein in modulating immunity.     

Effect of angiogenesis inhibitor TNP-470 on the progression of human gastric cancer xenotransplanted into nude mice

The effect of an angiogenesis inhibitor, TNP-470, on primary tumor growth, liver metastasis and peritoneal dissemination of gastric cancer was investigated by means of an orthotopic xenotransplanted model of 2 human gastric cancers, MT-2 and MT-5. TNP-470 showed a significant inhibitory effect on the growth of primary tumors after orthotopic transplantation of both xenografts when given at a dose of 30 mg/kg on alternate days from day 7 after transplantation (early treatment). However, growth of the MT-2 primary tumor was not inhibited by administration from day 14 after transplantation (late treatment). Liver metastasis was prevented significantly by early treatment of TNP-470. In particular, early treatment of MT-2 completely inhibited the development of macroscopic foci in the liver and was significantly more effective than late treatment. Peritoneal dissemination also was inhibited. Thus, TNP-470 was revealed to have strong inhibitory activity not only on primary tumors and liver metastases but also against peritoneal dissemination. These results suggest that this agent may provide a new approach to the treatment of gastric cancer.     

Dual role of betel leaf extract on thyroid function in male mice

The effects of betel leaf extract (0.10, 0.40, 0.80 and 2.0 g kg-1 day-1 for 15 days) on the alterations in thyroid hormone concentrations. lipid peroxidation (LPO) and on the activities of superoxide dismutase (SOD) and catalase (CAT) were investigated in male Swiss mice. Administration of betel leaf extract exhibited a dual role, depending on the different doses. While the lowest dose decreased thyroxine (T4) and increased serum triiodothyronine (T3) concentrations, reverse effects were observed at two higher doses. Higher doses also increased LPO with a concomitant decrease in SOD and CAT activities. However, with the lowest dose most of these effects were reversed. These findings suggest that betel leaf can be both stimulatory and inhibitory to thyroid function, particularly for T3 generation and lipid peroxidation in male mice, depending on the amount consumed.