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PubMed2005

Adjuvant therapy of breast cancer.

The treatment of early-stage breast cancer includes the use of chemotherapeutic and hormonal agents. Both chemotherapy and hormonal therapy have been shown by large, randomized trials to offer a survival advantage. The most commonly used chemotherapeutic agents used in the United States are doxorubicin and cyclophosphamide (AC). However, 3 studies have suggested that there may be an advantage in the use of taxanes in the adjuvant treatment of breast cancer. Furthermore the use of dose dense chemotherapy, incorporating AC and paclitaxel, has shown very promising results. It is well established that tamoxifen, a selective estrogen receptor modulator (SERM), improves overall survival (OS) in women with hormone receptor (HR) positive breast cancer. However, the results from large multicenter, randomized trials, suggest the potential superiority of aromatase inhibitors, compared to tamoxifen or an advantage of sequencing tamoxifen followed by an aromatase inhibitor (AI). The role of ovarian suppression is still being investigated in patients who have received prior chemotherapy. Newer agents, such as the monoclonal antibody against the HER2/neu receptor, trastuzumab, are now being studied as adjuvant therapy in early-stage breast cancer. In the next few years, with the completion of several large randomized trials, we will be able to answer several questions, including the optimal way of incorporating AIs into adjuvant therapy, the long-term sequella of using trastuzumab in the adjuvant treatment of breast cancer and the role of ovarian suppression combined with an aromatse inhibitor in premenopausal women with breast cancer.

Antineoplastic Agents↗
PubMed1998

[Fundamentals of hygiene to be used for stallions in an instrumental artificial insemination].

Equine artificial insemination (AI) meanwhile has been widely established in the warm blood horse industry. Because of its importance consistent hygienic aspects and their significance for the use of stallions as semen donors in AI-programs are presented and clarified. Incidence as well as importance of equine venereal infectious diseases are considered. Data of physiological bacterial genital flora and treatment principles of therapeutic control of venereal infectious bacterial agents as well as a model of control of Equine Viral Arteritis are given. A prophylactic hygiene program for donor stallions in routine AI including special microbiological monitoring is presented.

Animals↗
PubMed1991

Amphibian myocardial angiotensin II receptors are distinct from mammalian AT1 and AT2 receptor subtypes.

High-affinity receptors for angiotensin II were identified on Xenopus laevis cardiac membranes and characterized by binding-inhibition studies with peptide and non-peptide AII antagonists. Scatchard analysis of the binding data identified a high-affinity site with Kd1 = 1.6 nM and Bmax1 = 3.7 pmol/mg protein and a low-affinity site with Kd2 = 22 nM and Bmax 2 = 9.5 pmol/mg protein. Treatment with dithiothreitol reduced the number of binding sites by greater than 70%. The rank order of potency for ALL analogs was (agent, IC50) [Sar1,Ile8]AII, 0.91 nM greater than AII, 2.0 nM greater than AI, 5.3 nM greater than [Sar1, Ala8]AII, 19 nM much greater than CGP42112A, 1.2 microM much much greater than DuP 753 approximately PD-123177, greater than 100 microM. The relative potencies of these compounds differ markedly from their activities on the two known mammalian AII receptor subtypes, AT1 and AT2. These results indicate that amphibian AII receptors are pharmacologically distinct from both the AT1 and AT2 receptors characterized in mammalian tissues.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed2005

The effect of triptolide on CD4+ and CD8+ cells in Peyer's patch of SD rats with collagen induced arthritis.

Triptolide is a purified component from a traditional Chinese herb Tripterygium wilfordii Hook F. It has been shown to have anti-inflammatory and immunosuppressive activities by its inhibitory effect on T cells. But the effect of triptolide on Peyer's patch cells is unknown. Enteric mucosal immune system, including Peyer's patch, is regarded as one of the sites for inducing immunity tolerance, and this intolerance effect has been used to induce oral tolerance which can considerably reduce arthritis severity in several models of experimental polyarthritis and RA patients. In this study, we investigated the effect of triptolide on the Peyer's patch cells and peripheral lymphocytes in collagen induced arthritis (CIA) in rats. CIA in rat is a widely studied animal model of inflammatory polyarthritis with similarities to rheumatoid arthritis (RA). Our data show that triptolide could lower the arthritic scores and delay the onset of CIA. There are more Peyer's patches in triptolide treated rats than in control rats, while there is no difference in Peyer's patch numbers between CIA rats and triptolide treated rats. In the Peyer's patch, more CD4+ cells are observed in CIA rats, and the numbers of CD4+ cells in triptolide treated rats and control rats are similar. While more CD8+ cells are observed in triptolide treated rats, and the numbers of CD8+ cells in CIA rats and control rats are similar. In periphery, more CD4+ cells and less CD4+ cells in CIA rats and triptolide treated rats are respectively observed. Therefore, the regulation on Peyer's patch might explain some of the immunosuppressive activities of triptolide, and enteric immune response might be actively involved in CIA pathogenesis. It is suggested that the Peyer's patch is one of the primary targets of the immunosuppressive activity of triptolide.

Animals↗
PubMed2004

Chemiluminescence detection of isoniazid using Ru(phen)3(2+)-isoniazid-Ce(IV) system.

In our experiment, it was observed that isoniazid could enhance the chemiluminescence (CL) emission of tris-(1,10-phenanthroline)ruthenium(II) (Ru(phen)3(2+))-cerium(IV) (Ce(IV)) system and this enhancement effect was dependent on the concentration of isoniazid, based on which, a novel CL system was established for the detection of isoniazid. Under the optimum experimental conditions, the dynamic range and detection limit are 7.0 x 10(-2) to 6.5 microg ml(-1) and 2.5 x 10(-2) microg ml(-1), respectively. The R.S.D. is 3.4% (n = 11). The proposed method has been applied to detect the content of isoniazid in the injection solution with satisfactory results. The possible mechanism of the CL reaction was studied.

Calibration↗
PubMed1999

Diabetes and vascular impotence: does insulin dependence increase the relative severity?

AIM OF THE STUDY: Diabetes is a well documented risk factor for vascular erectile dysfunction (ED). We evaluated the relative roles of insulin dependence (IDDM) vs oral agent controlled diabetes (NIDDM) in predicting the etiologies and severity of ED: arterial insufficiency (AI), venous leakage (CVOD), and mixed vascular disease. The impact of additional risk factors were also analyzed: hypertension (HTN), coronary artery disease (CAD), and smoking (SM). METHODS: Retrospective data on 105 patients complaining of impotence who underwent pharmacotesting with PGE1 (Caverject) and color duplex Doppler was reviewed. Penile blood flow study (PBFS) data following a period of privacy and self-stimulation was compared. PBFS diagnostic criteria were: AI for peak systolic velocity (PSV) < 25 cm/s; CVOD for PSV > or = 35 cm/s and resistive index (RI) < 0.9; mixed vascular disease for PSV > or = 25 cm/s, PSV < 35 cm/s and RI > 0.9. Consistent dosing of PGE1 was used; 6 mcg for age < 60 y and 10 mcg for age > or = 60 y. Patients were NIDDM (79 out of 105) and IDDM (26 out of 105). Mean ages for NIDDM and IDDM were respectively 60, and 55 y. The relative significance of insulin dependence was assessed by Student's t-test. RESULTS: The most common etiology of ED was arterial insufficiency: mean PSV's did not significantly vary and were: 23.5 cm/s for NIDDM, and 21.6 cm/s for IDDM. PBFS parameters did not vary significantly for the risk factors of SM or HTN and diabetes. Mean peak systolic velocities were significantly different among diabetics with coronary artery disease: NIDDM/CAD, 22.9 cm/s compared to IDDM/CAD, 14.8 cm/s (P = 0.006). CONCLUSIONS: We found among the 105 diabetics the most common etiology of vascular ED based on Doppler criteria was arterial insufficiency, 64%. Statistical analysis of additional risk factors (SM, HTN, CAD) suggested that patients with IDDM and CAD have more severe cavernosal arterial insufficiency than patients with NIDDM and CAD. This data tends to support the theory that microangiopathy is the predominant factor in diabetic impotence, and that insulin dependent diabetes with 'large vessel' coronary heart disease have a similar pathology in the 'small vessels' regulating penile inflow which is unfortunately worse than their non-insulin dependent counterparts.

Alprostadil↗
PubMed1990

Effect of salvianolic acid A, a depside from roots of Salvia miltiorrhiza, on gastric H+,K(+)-ATPase.

Salvianolic acid A, a depside from the roots of Salvia miltiorrhiza, inhibited pig gastric H+,K(+)-ATPase and pNPPase with 50% inhibition values (IC50) of 5.2 x 10(-7) M and 1.7 x 10(-6) M, respectively. Kinetic studies revealed that the inhibition patterns induced by salvianolic acid A were competitive with respect to ATP and noncompetitive with respect to K+. Salvianolic acid A (25 mg/kg, i.p.) significantly inhibited acid secretion in pylorus-ligated rats. At the same dose it also showed a significant reduction in the formation of gastric lesion induced by water immersion and restraint stress. These results suggest that salvianolic acid A shows antisecretory and antiulcer activity by inhibiting the gastric H+,K(+)-ATPase.

Adenosine Triphosphatases↗
PubMed2005

Alteration of binding sites for [3H]P1075 and [3H]glibenclamide in renovascular hypertensive rat aorta.

AIM: The alterations of the binding sites for ATP-sensitive K+ channel (K(ATP)) openers and blockers in aortic strips were investigated in hypertensive rats. METHODS: Radioligand binding techniques were used to compare the specific binding properties of [3H]P1075 and [3H]glibenclamide (Gli) in normotensive (NWR) and reno-vascular hypertensive rat (RVHR) aortic strips. RESULTS: The KD values of [3H]P1075 binding were increased by 1.5-fold, while the Bmax values were unchanged in RVHR. The IC50 values of P1075 and pinacidil (Pin) for displacing the [3H]P1075 binding in RVHR were increased by 1.8- and 1.7-fold, respectively. The kinetic processes of association and dissociation of [3H]P1075 binding were slower in RVHR. Glibenclamide pretreatment slowed down the kinetic processes of the association and dissociation of [3H]P1075 binding in NWR, but failed to alter the kinetic processes of [3H]P1075 binding in RVHR. The IC50 values of Gli for displacing the [3H]Gli binding at high-affinity sites were increased by 3-fold, while those at low-affinity sites remained to be unchanged in RVHR. The kinetic processes of association of [3H]Gli binding were decreased and those of the dissociation were accelerated in RVHR. The treatment with Pin slowed down the association kinetic processes but accelerated the process of the dissociation of [3H]Gli binding in NWR, but did not alter the kinetics of [3H]Gli binding in RVHR. CONCLUSION: The affinity of binding sites for [3H]P1075 and of high-affinity binding sites for [3H]Gli are decreased, and the negative allosteric interactions between the two binding sites are impaired in RVHR aorta.

Animals↗
PubMed2005

In-vitro cytotoxicity, in-vivo biodistribution and anti-tumour effect of PEGylated liposomal topotecan.

In attempt to increase the accumulation of topotecan in tumours and improve its anti-cancer activity, PEGylated liposome (H-PEG) containing topotecan was prepared. The in-vitro cytotoxicity, in-vivo biodistribution pattern and anti-tumour effect of H-PEG were studied systemically. Compared with free topotecan or conventional liposome (H-Lip), H-PEG improved the cytotoxic effect of topotecan against human ovarian carcinoma A2780 and human colon carcinoma HCT-8 cells. The IC50 value (concentration leading to 50% cell-killing) of H-PEG decreased 5 fold (P<0.01) and 9 fold (P<0.01) against A2780 and HCT-8 cells compared with H-Lip, respectively. The results of biodistribution studies in sarcoma S(180) tumour-bearing mice showed that liposomal encapsulation increased the concentration of total topotecan and the ratio of lactone form in plasma. H-PEG resulted in a 70-fold and 3.7-fold increase in AUC(0-->24 h) compared with free topotecan and H-Lip, respectively. Moreover, H-PEG increased the accumulation of topotecan in tumours and the relative tumour uptake ratio compared with free topotecan was 5.2, and higher than that of H-Lip. The anti-cancer effect studies in murine heptocarcinoma H(22) tumour-bearing mice showed that H-PEG improved the therapeutic efficiency of topotecan and decreased the toxicity of topotecan to a certain extent compared with H-Lip. These results indicated that PEG-modified liposome might be an efficient carrier of topotecan.

Animals↗
PubMed2000

The effect of oxytocin antagonist on uterus in response to exogenous oxytocin.

This study was performed to determine the action mode of oxytocin antagonist. In Study 1, the duration of in vivo action of oxytocin antagonist I (AI) was examined. After infusing AI, oxytocin was given and repeated every hour for 5 hr. Uterine activities were monitored with a polygraph. Study 2 determined the effect of AI on uterine oxytocin receptor number (Rn) and binding affinity (Kd). AI treated rats were sacrificed at 0.5 and 4 hr later for receptor assay. In Study 1, the uterine contractile response to oxytocin was significantly inhibited (p<0.05) compared to controls at five min, 1 and 2 hr after injection of AI. No differences in response were detected compared to controls (p>0.05) at later hours. In Study 2, no differences (p>0.05) between the AI and control animals in either oxytocin receptor number or binding affinity was found. These data suggest that the major mode of AI action is via competitive inhibition at the uterine oxytocin receptor and not by altering receptor number or binding affinity. AI is suggested to have the potential of being a potent and specific tocolytic agent for prevention of preterm labor in human.

Animals↗
PubMed2006

Effects of huoxiangzhengqi liquid on enteric mucosal immune responses in mice with Bacillus dysenteriae and Salmonella typhimurium induced diarrhea.

AIM: To explore effects of huoxiangzhengqi liquid (HXZQ) on enteric mucosal immune responses in mice with Bacillus dysenteriae and Salmonella typhimurium induced diarrhea (BSD). METHODS: BSD was induced in Balb/c mice by oral administration with Bacillus dysenteriae and Salmonella typhimurium. HXZQ was administrated from the day of diarrhea induction at dosages of 5.21 g/kg and 0.52 g/kg, respectively. The onset of diarrhea and lasting time were recorded. Peyer's patches and peripheral lymphocytes were prepared for flow cytometry, and levels of TNF-alpha in peripheral blood and enteric tissue homogenates were determined with ELISA. Student's t test was employed for statistics. RESULTS: Mice in BSD group started showing continuous diarrhea on the day of induction until the fourth day when they were sacrificed. Diarrhea in the mice of HXZQ high and low dose groups lasted for 36 and 54 h, respectively. There were more CD4+ and CD8+ cells in peripheral blood, fewer CD4+ cells in Peyer's patches in BSD mice compared to normal mice. Fewer CD4+ and CD8+ cells was shown in the mice in HXZQ high group compared to BSD mice. In Peyer's patch, there were more CD8+ cells in mice in HXZQ high and low dose groups and more CD4+ in mice in HXZQ high group. Higher levels of TNF-alpha in peripheral blood and intestinal tissue homogenates in BSD group were observed. Mice in HXZQ high group showed decreased levels of TNF-alpha in peripheral blood and enteric tissue homogenates. CONCLUSION: The immune regulation of CD4+ and CD8+ cells in Peyer's patch and suppression of TNF-alpha levels in enteric homogenates may partially explain the effect of HXZQ on improvement of BSD.

Animals↗
PubMed1999

Treatment options in androgen-independent prostate cancer.

Metastatic prostate cancer is a leading cause of cancer-related death in men. Although most patients will respond to androgen ablation as initial systemic therapy, nearly all patients will develop androgen-independent prostate cancer (AI CaP) and will succumb to the disease. Advances in molecular biology have demonstrated mutations in and persistent expression of the human androgen receptor in metastatic disease. Furthermore, recent evidence indicates that an apoptotic block through p53 mutations or bcl-2 overexpression may have a potential role in the poor responses seen with standard chemotherapy. Presently, the six general treatment options available for AI CaP are best supportive care, radiation therapy, radioisotopes, secondline hormonal therapy, chemotherapy (single agent or combination), and investigational therapies such as monoclonal antibodies, cyclin-dependent kinase inhibitors, matrix metalloproteinase inhibitors, and antiangiogenesis agents, among others. None of these modalities have produced durable remissions, although some have demonstrated palliative benefit. The next generation of clinical trials should not consist of futile hormonal manipulations or repetitive chemotherapy. Therapeutic strategies aimed at circumventing molecular blocks to cell death or targeting unique cancer molecules and genes will be more likely to improve quality of life and longevity. Furthermore, the aggressive use of palliative care will ensure effective caring for patients and the healing of families in the absence of cure.

Adenocarcinoma↗
PubMed2003

[Recombinant human interleukin-11 in the prevention of chemotherapy-induced thrombocytopenia].

OBJECTIVE: To evaluate the efficacy and toxicity of domestic recombinant human interleukin-11 (rhIL-11) in the prevention of chemotherapy-induced thrombocytopenia. METHODS: A randomized, self-crossover and placebo-controlled trial was conducted, with rhIL-11 and placebo classified randomly as drug A and drug B. Patients were randomly assigned to group AB or group BA. 25 microg/kg body weight of drug A or drug B was administered subcutaneously once daily starting 24 hours after chemotherapy and continued for 7 to 14 days or until the platelet count reached > or = 300 x 10(9)/L. RESULTS: 118 patients were evaluable in the efficacy study. When compared with the placebo treated cycle, the results showed that rhIL-11 was able to significantly increase the platelet count at the nadir and d21 after chemotherapy, with a increase of 60.7% and 86.1% (both P < 0.001). The mean duration of thrombocytopenia (< 100 x 10(9)/L) in rhIL-11 treated cycle was 1.0 +/- 2.0 days as compared to 6.9 +/- 5.3 days in placebo treated cycle. The side effects were ache (24.6%), swelling (16.1%) and knurl (11.9%) at the injection site, hyperaemia of conjunctiva (16.1%), edema (8.5%), palpitation (6.8%) and fatigue (5.1%). CONCLUSION: rhIL-11, possessing significant thrompoietic activity, significantly increases the likelihood of avoiding chemotherapy-induced thrombocytopenia and shorten the duration of thrombocytopenia. Its side effects are mild and manageable.

Adolescent↗
PubMed2003

[Effects of realgar on tissue factor expression of NB4 and MR2 cells].

OBJECTIVE: To investigate the effects of Realgar on procoagulant activity (PCA), tissue factor expression and tissue factor mRNA transcription in acute promyelocytic leukemia (APL) cell lines NB4 and MR2 cells. METHOD: NB4 and MR2 cells were treated with 300 micrograms.L-1 Realgar PCA of the treated cells was detected using one-stage clotting assay. TF antigen was detected by ELISA and TFmRNA by semi-quantitive RT-PCR. RESULT: The PCA and TF antigen level in NB4 and MR2 cells were significantly higher than that in HL-60 and K562 cells. Realgar could down-regulate the membrane PCA, TF antigen and TF mRNA transcription of NB4 and MR2 cells in a time-dependent manner. CONCLUSION: Down-regulating TF expression and PCA of NB4 and MR2 cells by Realgar may be one of the mechanism of its improvement effect on DIC-related hemorrhage of APL patients.

Antineoplastic Agents↗
PubMed2004

[Effects of genistein on NOS, GSH-Px activities and NO, GSH, MDA contents in MCF human breast cancer cells].

OBJECTIVE: To investigate the mechanism that the genistein inhibit the MCF human breast cancer cell. METHODS: The activities of glutathione peroxidase (GSH-Px), nitric oxide synthetase (NOS) and the contents of nitric oxide (NO), glutathione (GSH), malondialdehyde (MDA) both in culture supernatant and cells were examined by enzyme method and spectrophotometry respectively. RESULTS: With genistein increasing, the activities of GSH-Px, NOS and the contents of NO increased significantly (P < 0.05), while the contents of GSH, MDA decreased both in culture supernatant and cells (P < 0.05). CONCLUSION: Genistein can affect NO synthesis and antioxidation in MCF breast cancer cells. It may be one of the mechanisms that the genistein inhibit the MCF breast cancer cells growth.

Antineoplastic Agents↗