The protective effect of Shenfu injection against elderly severe pneumonia.

OBJECTIVE: The purpose of this study is to investigate the effect of Shenfu injection (SFI) on the tumor necrosis factor-α (TNF-α) and the interleukin (IL-6, IL-8, IL-10) of elderly patients who suffered from severe pneumonia. METHODS: From June 2012 to September 2014, we performed in our department 89 cases of elderly patients with severe pneumonia. These patients were randomly divided into two groups: the treatment group (45 cases) and the control group (44 cases). The control group was given the treatment of anti-infection, reducing sputum, and support therapy, while the treatment group was fed by SFI intravenously based on the control group. The TNF-α and the interleukin were detected by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the changes in the inflammatory response indicators, the blood gas analysis, and the parameters of vital signs were measured and compared before and after therapy. RESULTS: Prior to treatment, there is no significant difference between the treatment group and the control group (p > 0.05); after the treatment for 7 days, the levels of TNF-α, IL-6, and IL-8 were significantly decreased, while the level of IL-10 was obviously increased. The APACHE II score was significantly decreased in comparison to that before the treatment (p < 0.05), and the time of mechanical ventilation, the duration of time in ICU, and the application time of vasoactive drugs were notably shortened. CONCLUSION: The application of Shenfu injection exhibited a positive and effective effect on removing the inflammation media during the treatment of elderly severe pneumonia.

[Protective effect of Angelica sinensis polysaccharide against liver injury induced by D-galactose in aging mice and its mechanisms].

OBJECTIVE: To investigate the protective effect of Angelica sinensis polysaccharide (ASP) against liver injury induced by D-galactose in aging mice and its mechanisms. METHODS: Male C57BL/6J were randomly divided into three groups with 10 mice in each group. In the D-galactose model group, the mice were subcutaneously injected with D-galactose (120 mg/kg) qd×42; in the ASP+D-galactose group, from the 8th day of the establishment of D-galactose model, the mice were subcutaneously injected with ASP (120 mg/kg) qd×35. In the normal control group, the mice were subcutaneously injected with isotonic saline of the same volume at the same time point. On the 2nd day after the injection was finished, the ocular blood was collected to prepare serum and measure the content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil). The liver tissue homogenate was prepared to measure the content of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and advanced glycation end products (AGEs). A paraffin section of liver tissue was prepared; HE staining was performed to observe the pathomorphological changes of the liver, periodic acid-Schiff staining (PAS) was used to observe the changes in glycogen in the liver, and a transmission electron microscope was used to observe the hepatocyte ultrastructure. RESULTS: The D-galactose model group had increased content of ALT, AST, and TBil, reduced activities of SOD and GSH-Px, an increased content of MDA, and severe liver injuries; the hepatocytes showed degenerative changes, the amount of glycogen in the liver decreased, and the accumulation of AGEs increased. The ASP+D-galactose group had reduced content of ALT, AST, and TBil, increased activities of SOD and GSH-Px, and reduced content of MDA and AGEs; the amount of glycogen in the liver increased, and liver injury and hepatocyte injury were alleviated. CONCLUSION: ASP can antagonize the liver injury induced by D-galactose in aging mice, and its mechanism may be related to the inhibition of oxidative stress.

Flavonoids as potential anti-hepatocellular carcinoma agents: recent approaches using HepG2 cell line.

Numerous studies have documented that in cancer therapy flavonoids extracted from traditional Chinese medicine have anti-tumor activity or can enhance efficiency of chemotherapy in combination with chemotherapeutics. Thus, an awareness of flavonoids is needed by physicians and medical researchers. This review provides evidence about anti-hepatocellular carcinoma activity of flavonoids. First, as a common employed in vitro model, profile of HepG2 is shown. Second, the intracellular signaling pathways induced by flavonoids which inhibit the HepG2 cell line are summarized. Third, study situation of anti-HBV/HCV activity of flavonoids is shown. Our review is aimed at providing an understanding of anti-HBV/HCV activity and anti-HCC mechanisms of flavonoids, and an outlook on flavonoids application on cancer therapy.

Pollen limitation and Allee effect related to population size and sex ratio in the endangered Ottelia acuminata (Hydrocharitaceae): implications for conservation and reintroduction.

Small populations may suffer more severe pollen limitation and result in Allee effects. Sex ratio may also affect pollination and reproduction success in dioecious species, which is always overlooked when performing conservation and reintroduction tasks. In this study, we investigated whether and how population size and sex ratio affected pollen limitation and reproduction in the endangered Ottelia acuminata, a dioecious submerged species. We established experimental plots with increasing population size and male sex ratio. We observed insect visitation, estimated pollen limitation by hand-pollinations and counted fruit set and seed production per fruit. Fruit set and seed production decreased significantly in small populations due to pollinator scarcity and thus suffered more severe pollen limitation. Although frequently visited, female-biased larger populations also suffered severe pollen limitation due to few effective visits and insufficient pollen availability. Rising male ratio enhanced pollination service and hence reproduction. Unexpectedly, pollinator preferences did not cause reduced reproduction in male-biased populations because of high pollen availability. However, reproductive outputs showed more variability in severe male-biased populations. Our results revealed two component Allee effects in fruit set and seed production, mediated by pollen limitation in O. acuminata. Moreover, reproduction decreased significantly in larger female-biased populations, increasing the risk of an Allee effect.

Anti-interleukin-12/23p40 antibody attenuates chronic rejection of cardiac allografts partly via inhibition γδT cells.

In our previous study, we showed that treatment with an anti-interleukin (IL)-12/23p40 antibody inhibits acute cardiac allograft rejection via inhibiting production of interferon (IFN)-γ and IL-17a. However, the impact of this antagonistic anti-p40 antibody on chronic cardiac rejection was unclear. Hearts of B6.C-H2bm12/KhEg mice were transplanted into major histocompatibility complex (MHC) class II-mismatched C57Bl/6J mice (wild-type, γδTCR (-/-) and IL-17(-/-) ), which is an established murine model of chronic allograft rejection without immunosuppression. The mice were treated with control immunoglobulin (Ig)G or 200 µg anti-p40 monoclonal antibody on post-operative days, respectively. Abdominal palpation and echocardiography were used to monitor graft survival. The mice administered with anti-p40 antibody showed a significant promotion in graft survival (median survival time >100 days), and histological analyses revealed that cardiac allograft rejection was attenuated. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence analyses demonstrated that anti-p40 antibody down-regulated the level of ingraft cytokine and chemokine expression (IL-6, IFN-γ, IL-17a, CCL2 and CCL20). Flow cytometry analyses showed that γδ T cells are an important ingraft source of IFN-γ and IL-17a and inhibit the production of inflammation cytokine by anti-p40 antibody. Compared with the wild-type group, the graft survival time in the γδ T cell receptor(-/-) and IL-17(-/-) mice was prolonged significantly. Therefore we propose that, in the chronic allograft rejection model, treatment with anti-p40 antibody prolongs graft survival possibly by reducing the amount of reactive inflammatory cells, especially γδ T cells.

Cloning and characterization of the calreticulin gene in Asian seabass (Lates calcarifer).

Calreticulin (CRT) is a Ca2+-binding molecular chaperone in the endoplasmic reticulum. We cloned and characterized the CRT gene in an important marine food fish species Asian seabass (Lates calcarifer). The full-length DNA of the CRT gene was 2194 bp, including a complete open reading frame encoding 420 amino acid residues, a 113 bp 5'-untranslated region and an 818 bp 3'-untranslated region. The CRT gene contained nine exons and eight introns covering a total of 2772 bp genomic DNA from the start to stop codon. Ten single nucleotide polymorphisms (SNPs) were detected in introns and an exon in six individuals collected from five different locations. The CRT gene was assigned to linkage group 4 of the linkage map of Asian seabass. Quantitative real-time PCR revealed that the CRT gene was highly expressed in liver at the age of 1, 3 and 7 months under normal conditions, whereas its expression in liver reduced sharply after 0.5 to 2 h cold challenge at 16°C, and then increased slowly. A preliminary association analysis showed a significant (P < 0.001) association between the SNP6 in the CRT gene and the mortality after cold challenge at 16°C. Our results suggest that the CRT gene is associated with cold tolerance of Asian seabass and further investigation will be necessary to illustrate the underlying mechanisms.

Presynaptic inhibition of GABAergic synaptic transmission by adenosine in mouse hypothalamic hypocretin neurons.

Hypocretin neurons in the lateral hypothalamus, a new wakefulness-promoting center, have been recently regarded as an important target involved in endogenous adenosine-regulating sleep homeostasis. The GABAergic synaptic transmissions are the main inhibitory afferents to hypocretin neurons, which play an important role in the regulation of excitability of these neurons. The inhibitory effect of adenosine, a homeostatic sleep-promoting factor, on the excitatory glutamatergic synaptic transmissions in hypocretin neurons has been well documented, whether adenosine also modulates these inhibitory GABAergic synaptic transmissions in these neurons has not been investigated. In this study, the effect of adenosine on inhibitory postsynaptic currents (IPSCs) in hypocretin neurons was examined by using perforated patch-clamp recordings in the acute hypothalamic slices. The findings demonstrated that adenosine suppressed the amplitude of evoked IPSCs in a dose-dependent manner, which was completely abolished by 8-cyclopentyltheophylline (CPT), a selective antagonist of adenosine A1 receptor but not adenosine A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl) xanthine. A presynaptic origin was suggested as following: adenosine increased paired-pulse ratio as well as reduced GABAergic miniature IPSC frequency without affecting the miniature IPSC amplitude. Further findings demonstrated that when the frequency of electrical stimulation was raised to 10 Hz, but not 1 Hz, a time-dependent depression of evoked IPSC amplitude was detected in hypocretin neurons, which could be partially blocked by CPT. However, under a higher frequency at 100 Hz stimulation, CPT had no action on the depressed GABAergic synaptic transmission induced by such tetanic stimulation in these hypocretin neurons. These results suggest that endogenous adenosine generated under certain stronger activities of synaptic transmissions exerts an inhibitory effect on GABAergic synaptic transmission in hypocretin neurons by activation of presynaptic adenosine A1 receptors, which may finely regulate the excitability of these neurons as well as eventually modulate the sleep-wakefulness.

Activity-dependent release of adenosine inhibits the glutamatergic synaptic transmission and plasticity in the hypothalamic hypocretin/orexin neurons.

The hypocretin (orexin) neurons in the lateral hypothalamus play a crucial role in the promotion of arousal. Adenosine, an endogenous sleep-promoting factor, modulates both neuronal excitatory and synaptic transmission in the CNS. In this study, the involvement of endogenous adenosine in the regulation of excitatory glutamatergic synaptic transmission to hypocretin neurons was investigated in the hypothalamic slices from transgenic mice by using different frequencies of stimulation. A train of low-frequency stimulation (0.033, 1 Hz) had no effect on the amplitude of evoked excitatory postsynaptic currents (evEPSCs) in hypocretin neurons. Blockade of adenosine A1 receptors with selective A1 receptor antagonist 8-cyclopentyltheophylline (CPT), the amplitude of evEPSCs did not change during 0.033 and 1 Hz stimuli. When the frequency of stimulation was increased upto 2 Hz, a time-dependent depression of amplitude was recorded in hypocretin neurons. Administration of CPT caused no significant change in depressed synaptic response induced by 2 Hz stimulus. While depression induced by 10 and 100 Hz stimuli was partially inhibited by the CPT but not by the selective A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl)xanthine. Further findings have demonstrated that high-frequency stimulation could induce long-term potentiation (LTP) of glutamatergic synaptic transmission to hypocretin neurons in acute hypothalamic slices. The experiments with CPT suggested that A1 receptor antagonist could facilitate the induction of LTP, indicating that endogenous adenosine, acting through A1 receptors, may suppress the induction of LTP of excitatory synaptic transmission to hypocretin neurons. These results suggest that in the hypothalamus, endogenous adenosine will be released into extracellular space in an activity-dependent manner inhibiting both basal excitatory synaptic transmission and LTP in hypocretin neurons via A1 receptors. Our data provide further support for the notion that hypocretin neurons in the lateral hypothalamus may be another important target involved in the endogenous adenosine modulating the sleep and wakefulness cycle in the mammalian CNS.

Honeybees enhance reproduction without affecting the outcrossing rate in endemic Pedicularis densispica (Orobanchaceae).

There has been substantial debate in recent years surrounding the impact of introduced honeybees on native biota. This study reports on an investigation of Pedicularis densispica, a subalpine annual herb endemic to Southwest China, in an attempt to determine the impact of introduced domestic honeybees on pollen dispersal and thus on their reproductive success and mating system. Honeybees were introduced into the study site in 2004, and a sudden seasonal pollinator shift from bumblebees to honeybees was observed. Intra- and inter-plant visits by different pollinators were recorded in the field in 2003 and 2004. Fruit and seed sets prior to and after the pollinator shift were measured. Experimental pollinations were performed to characterize the breeding system. Outcrossing rates at the seed stage were estimated for both years using RAPD markers. Our results indicated that honeybees foraged between plants more frequently than bumblebees did. Our results also revealed that the introduction of honeybees significantly enhanced reproductive success. However, no significant difference was detected between the outcrossing rates due to bumblebee and honeybee pollination. P. densispica was almost completely outcrossing ( T(m) = 0.956 and 0.967, respectively in 2003 and 2004) but partially self-compatible. This study presents the first report of the outcrossing rate in the genus pedicularis and reveals a limited influence of pollination on the mating system in P. densispica. The pollinator shift did not reduce reproductive success of the plants and honeybees may be used to augment pollinator services for nectariferous P. densispica.

Schizophrenia trials in China: a survey.

OBJECTIVE: China's biomedical research activity is increasing and this literature is becoming more accessible online. Our aim was to survey all randomized control schizophrenia trials (RCTs) in one Chinese bibliographic database. METHOD: Chinese Academic Journals was electronically searched for RCTs and all relevant citations were also sought on PubMed to ascertain global accessibility. RESULTS: The search identified 3275 records, of which 982 were RCTs relevant to schizophrenia. A total of 71% (699) could be found by using English phrases. All the main body of text of the 982 papers was in Mandarin. On average, these trials involved about 100 people, with interventions and outcome measures familiar to schizophrenia trialists worldwide. Four of the 982 records (<1%) were identified on PubMed. CONCLUSION: Those undertaking systematic reviews should search the Chinese literature for relevant material. Failing to do this will leave the results of systematic reviews prone to random error or bias, or both.

Chinese herbal medicine for schizophrenia.

BACKGROUND: Traditional Chinese medicine (TCM) was the main form of treatment in China for psychiatric illnesses until the development of antipsychotic drugs in the 1950's. Antipsychotic drugs have become the primary intervention for schizophrenia, although herbal medicines can still form part of the treatment. OBJECTIVES: To review Chinese herbal medicine, used alone or as part of a TCM approach, for people with schizophrenia and related psychoses. SEARCH STRATEGY: We undertook electronic searches of the Cochrane Schizophrenia Group's register (December 2003), the Traditional Chinese Medical Literature Analysis and Retrieval Database (TCMLARS) (October 2003), Chinese Biomedical Database (CBM) (December 2003), China National Knowledge Infrastructure Database (May 2004), Complementary Medicine Database (AMED) (December 2003). We contacted the Chinese Cochrane Centre, the Cochrane Complementary Medicine Field and first authors of included studies and inspected reference lists for additional studies. SELECTION CRITERIA: We included all relevant randomised controlled trials involving people with schizophrenia-like illnesses, allocated to Chinese herbal medicine, including any Chinese herbs (single or mixture), compared with placebo/no treatment or antipsychotic drugs. DATA COLLECTION AND ANALYSIS: We independently extracted data and calculated fixed effects relative risk (RR), the 95% confidence intervals (CI) for homogeneous dichotomous data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: Only one small trial of the seven included studies truly evaluated TCM for schizophrenia. The other trials evaluated Chinese herbs for schizophrenia. We found one study comparing Chinese herbal medicine with antipsychotic drugs. Data for the global state outcome 'no change/worse' favoured people allocated to antipsychotic medication (n=90, RR 1.88 CI 1.2 to 2.9, NNH 4 CI 2 to 12). Six trials compared Chinese herbal medicine in combination with antipsychotic with antipsychotic drugs alone. One trial found global state 'not improved/worse' favoured the herbal medicine/antipsychotic combination (n=123, RR 0.19 CI 0.1 to 0.6, NNT 6 CI 5 to 11). Two studies (n=103) also found short-term data from the Clinical Global Impression scale favoured the herbal medicine plus antipsychotic group (WMD -0.46 CI -0.9 to -0.1) compared with those given only antipsychotics. Significantly fewer people in the experimental group left the study early compared with those given antipsychotics alone (n=1004, 6 RCTs, RR 0.30 CI 0.16 to 0.58, NNT 21 CI 18 to 35). Reports of constipation were significantly lower in the treatment group compared to those receiving antipsychotics (n=67, 1 RCT, RR 0.03 CI 0.0 to 0.5, NNH 2 CI 2 to 4). AUTHORS' CONCLUSIONS: Chinese herbal medicines, given in a Western biomedical context, may be beneficial for people with schizophrenia when combined with antipsychotics. Traditional Chinese medicine is also under-evaluated, but results from one pioneering study that attempted to evaluate TCM should encourage further trials.

Acupuncture for schizophrenia.

BACKGROUND: Acupuncture has been shown to be a relatively safe health care intervention with few adverse effects. In contrast ,antipsychotic drugs can have seriously disabling adverse effects. However, the benefits of acupuncture in the treatment of schizophrenia are unclear, and further evidence is needed to inform clinicians and people with schizophrenia of its efficacy in the treatment of schizophrenia. OBJECTIVES: To evaluate acupuncture for people with schizophrenia and related psychoses. SEARCH STRATEGY: We (JR, JX) undertook electronic searches of the Cochrane Schizophrenia Group's register (April 2005). We inspected reference lists and contacted the first author of each included study. SELECTION CRITERIA: We included all relevant randomised controlled trials involving people with schizophrenia-like illnesses, allocated to acupuncture, electro-acupuncture, laser-acupuncture, placebo, no treatment, or antipsychotic drugs produced by pharmaceutical companies were included. DATA COLLECTION AND ANALYSIS: We independently extracted the data. For homogeneous dichotomous data, the fixed effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, we calculated weighted mean differences with 95% CI. MAIN RESULTS: We included five trials. Two trials comparing acupuncture to antipsychotics were equivocal for global state and leaving the study early. Extrapyramidal adverse events were significantly lower in the acupuncture group (n=21, RR 0.05 CI 0.0 to 0.8, NNT 2 CI 2 to 8). Four out of the five trials also compared acupuncture combined with antipsychotics to antipsychotics alone. Global state outcomes and leaving the study early were equivocal. BPRS endpoint data (short term) favoured the combined acupuncture and antipsychotic group (n=109, RR -4.31 CI -7.0 to -1.6), although dichotomised BPRS data 'not improved' confounded this outcome with equivocal data. Depression scores HAMD (n=42, WMD -10.41 CI -12.8 to -8.0), HAMD 'not improved' (n=42, RR 0.17 CI 0.1 to 0.5, NNT 2 CI 2 to 3) and ZDS (n=42, WMD -24.25 CI -28.0 to -20.5) significantly favoured the combined acupuncture/antipsychotic treatment group, although results were from single, small studies. Treatment emergent adverse events scores were significantly lower in the acupuncture/antipsychotic group (n=40, WMD -0.50 CI -0.9 to -0.1), again from a single, small study. AUTHORS' CONCLUSIONS: We found insufficient evidence to recommend the use of acupuncture for people with schizophrenia. The numbers of participants and the blinding of acupuncture were both inadequate, and more comprehensive and better designed studies are needed to determine the effects of acupuncture for schizophrenia.

A study of neonatal swimming (water therapy) applied in clinical obstetrics.

OBJECTIVE: To study the significance of some clinical parameters related to neonatal 'swimming' (water therapy) during hospitalization. METHODS: Normal newborns were randomly divided into two groups to observe their birth weight, weight before discharge,time of first defecation and meconium turning yellow. Group one was the swimming (study) group, comprising a total of 223 newborns including 127 babies delivered after spontaneous vaginal delivery and 96 babies after Cesarean section. Group two was the bathing (control) group, comprising 154 newborns including 109 babies delivered after spontaneous vaginal delivery and 45 babies after Cesarean section. RESULTS: There was no significant difference in birth weight between the two groups (p > 0.05). However, the mean weight before discharge of the babies in the study group was 3.29 + 0.35 and 3.51 + 0.40 kg, spontaneous vaginal delivery vs. Cesarean section, compared with 3.09 + 0.38 and 3.17 + 0.48 kg, respectively, in the control group (p < 0.01). The corresponding mean times of meconium turning yellow were 39.15 + 15.88 and 39.02 + 13.60 h in the study group compared with 48.01 + 19.42 and 55.67 + 25.05 h in the control group. This difference was significant (p < 0.01), as was the difference between the time of first defecation (p < 0.05). CONCLUSION: Neonatal swimming can accelerate babies' growth in the early stage.

[Effect of yiqi yangyin huoxue recipe on endothelin and nitric oxide of type 2 diabetic patients with deficiency of both Qi-Yin and blood stasis syndrome].

OBJECTIVE: To study the effect of Yiqi Yangyin Huoxue recipe (YQYYHX) in treating type 2 diabetes mellitus (DM) patients with deficiency of both Qi-Yin (DQY) and blood stasis Syndrome. METHODS: Forty-one type 2 DM patients compared with those in the control group were observed. RESULTS: After treatment, the endothelin (ET) level of the treated group reduced significantly, and the total effective rate of blood sugar lowering were as follows: Fasting blood glucose (FBG) 87.80%, 2 hours postprandial plasma blood glucose (PBG) 90.24%. CONCLUSION: YQYYHX is effective in improving the patient's vascular endothelia cell functions by reducing the plasma ET level, clinical symptoms and blood sugar lowering.

[Effect of Tripterygium polyglycoside on interleukin-6 in patients with Guillain-Barre syndrome].

OBJECTIVE: To study the action of interleukin-6(IL-6) in pathogenesis and effect of patients with Guillain-Barre syndrome (GBS). METHODS: Forty-three patients of GBS were selected according to Asbury's standard and divided into two groups on layer randomize principle, they were treated with adrenal corticosteroid and Tripterygium polyglycoside (TP) respectively. Serum and cerebrospinal fluid (CSF) content of IL-6 were measured by double antibody sandwich ELISA method. RESULTS: (1) The serum and CSF content of IL-6 in GBS group was higher than those in the normal control group significantly; (2) There was positive correlation between CSF IL-6 and clinical severity (P < 0.01) before treatment; (3) After treatment the clinical symptoms were improved in both groups, but the TP treated group showed better effect than the control group in improving symptoms and lowering serum IL-6 level (P < 0.05). CONCLUSION: CSF level of IL-6 could be taken as one of the criteria for severity evaluation of patient's condition. TP is superior in suppressing abnormal immune reaction to adrenal corticosteroid in GBS patients.

Effect of antiangiogenic agents on experimental animal models of hepatocellular carcinoma.

A new therapeutic strategy for treating metastasis in hepatocellular carcinoma (HCC) has entailed the use of antiangiogenic agents such as suramin, BB-94 (Batimastat), TNP-470, and carboxyamido-triazole (CAI, a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis). These agents have been used to treat metastatic model of HCC in nude mouse (LCI-D20 mouse model). The results of these studies are summarized in this paper with emphasis on the inhibitory effects of the drugs on tumour growth, angiogenesis, invasion and metastasis in LCI-D20 mouse models. The results suggest that all of the agents used can significantly inhibit tumour growth, angiogenesis, invasion and metastasis of human HCC in nude mouse models, and may be candidates for the control of recurrence and metastasis after HCC resection.

Chronic ethanol and iron administration on iron content, neuronal nitric oxide synthase, and superoxide dismutase in rat cerebellum.

Excessive chronic ethanol administration to animals has been shown to cause oxidative insults to many body organs, including the liver and brain. In many instances, iron supplementation to the diet may further aggravate ethanol-induced liver damage. However, whether increased dietary iron can enhance the damage in the brain is unknown. In this study, four groups of Sprague-Dawley rats were fed a Lieber-DeCarli liquid diet containing 5% (w/v) ethanol or isocaloric amount of maltase and/or 0.25% (w/v) carbonyl iron for 2 months. At the end of the feeding regimen, iron contents were determined in the plasma, liver, cerebral cortex, and cerebellum. Cerebellar superoxide dismutase (SOD) and nitric oxide synthase (NOS) activities were measured and mRNA levels of MnSOD, CuZnSOD, and nNOS in the cerebellar granule cell layer were quantitated by in situ hybridization. Ethanol treatment alone caused an increase in iron levels in plasma, no change in the liver and cerebral cortex, but a decrease in the cerebellum. Iron supplementation increased liver iron >4-fold but did not alter iron contents in the cerebellum and cortex. All of the mRNA species examined and SOD activity were not affected by either iron or ethanol administration. However, NOS activity in the cerebellum was significantly enhanced by ethanol, whereas iron supplementation had an opposite effect. Our results indicate that iron supplementation to animals consuming ethanol may have tissue-specific effects. Furthermore, ethanol-induced increase in NOS activity in the cerebellum may explain the sensitivity of cerebellar neurons to oxidative insult.

Dietary supplementation of grape polyphenols and chronic ethanol administration on LDL oxidation and platelet function in rats.

Polyphenolic compounds have been implicated as the active ingredients for the cardiac protective effect in red wine. We tested the effects of dietary supplementation of polyphenols from grape (GP) and chronic ethanol administration on low-density-lipoprotein (LDL) oxidation and platelet function in rats. Four groups of young male Sprague-Dawley rats were fed the following diets for 2 months: (I) a high fat Lieber-DeCarli liquid diet with an isocaloric amount of maltose, (II) with 5% ethanol (w/v), (III) with 5 mg/dL of GP, and (IV) ethanol plus GP. Platelet aggregation was induced by thrombin and phorbol myristate acetate (PMA) and LDL oxidation was induced by Cu2+. Chronic ethanol administration resulted in a significant increase in LDL oxidation and this effect was partially protected by supplementation with GP. Although platelet number was not affected by either ethanol or GP administration, platelet aggregation induced by thrombin was reduced in ethanol, GP and ethanol plus GP groups as compared to controls. On the other hand, platelet aggregation induced by PMA was not altered in any groups, suggesting that protein kinase C was not a causal factor for the reduction of aggregatory response induced by thrombin. These results show similar effects of ethanol and GP on platelet aggregation but different effects on LDL oxidation. It can be concluded that dietary supplementation with GP may exert partial protection on oxidative insults such as those elicited by chronic ethanol ingestion.

[An experimental study of angiogenesis inhibitor TNP-470 on tumor growth and metastasis of Lewis lung carcinoma].

OBJECTIVE: The inhibition effect of angiogenesis inhibitor TNP-470 on tumor growth and metastasis was studied using Lewis lung carcinoma. METHODS: Lewis lung carcinoma cells(2.4 x 10(6)/mouse) were inoculated subcutaneously to 20 mice, they were randomized into 2 groups. From the 2nd day, the treated group was given 40 mg/kg of TNP-470 s.c. q.o.d. (8 times) and the control group was given vehicle only (3% ethanol). On the 22nd day, the weight of the subcutanous tumors and the lung metastasis rates of the 2 groups were detected. The results were analysed by Student-t and chi 2 test. RESULTS: The tumor weight of the control and treated group was 3.77 +/- 1.05 g and 1.98 +/- 0.96 g, respectively (P = 0.0009). The lung metastasis rate of the control and treated group was 80%(8/10) and 30%(3/10), respectively (P = 0.03). CONCLUSION: These results suggest that the angiogenesis inhibitor TNP-470 has a strong inhibitory effect both on growth of the primary tumor and metastasis of Lewis lung carcinoma.