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At least 307 records · Page 17Linked to original sources
PubMed2005

Vascular effects of aromatase inhibitors: data from clinical trials.

Aromatase inhibitors (AIs) are becoming the endocrine treatment of first choice for postmenopausal women with hormone receptor-positive breast cancer and are under investigation for use in breast cancer prevention. AIs reduce circulating estrogen to barely detectable concentrations. It is possible that such a low concentration will be deleterious to the vascular system since estrogen receptors are known to be in the cell walls of blood vessels and estrogen is thought to be important in maintaining blood vessel integrity. Because most women who present with primary breast cancer are cured by surgery and systemic therapy and the major cause of female death is vascular disease, it is particularly important to investigate the vascular side effects of AIs in current breast cancer adjuvant and prevention trials. In order to set the vascular toxicities of AIs reported in the current adjuvant trials into context, here we compare them with the toxicities seen during treatment with hormone replacement therapy (HRT) and selective estrogen receptor modulators (SERMs). Clinical trial evidence indicates that HRT increases risk of coronary heart disease (CHD) whereas SERMs and AIs (to date) appear to be neutral. Cerebrovascular disease and venous thromboembotic events are increased by HRT and SERMs but appear to be unaffected by treatment with AIs. Cognitive function is also considered here since it may also have a vascular component and is potentially a serious potential side effect/benefit of AIs. Recent studies indicate that HRT has a small detrimental effect on cognitive function and is associated with a doubling of the incidence of dementia. A comprehensive study of the SERM, raloxifene, on cognitive function showed no significant effect. There are no definitive reported studies investigating tamoxifen and none for AIs on cognitive function, although there is one in progress in the context of the IBIS II prevention trial which compares anastrozole to placebo in women at high risk. At present concerns about deleterious vascular side effects are confined to HRT and SERMs. However, we have few long-term data using AIs for the treatment and prevention of breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed1998

Salicylate and quinine selectively increase spontaneous firing rates in secondary auditory cortex.

This study presents firing rates for simultaneously recorded spontaneous and stimulus driven multi-unit activity in primary auditory cortex (AI), anterior auditory field (AAF) and secondary auditory cortex (AII) in cats before and after application of salicylate or quinine. From 21 cats, in three cortical areas simultaneously, a total of 1533 multi-unit files were obtained. The data suggest (1) that both salicylate and quinine significantly increase spontaneous firing rates in AII, whereas in AI and AAF both quinine and salicylate reduced the spontaneous rate; (2) the effect of both drugs was to increase spontaneous rates for recording sites with high characteristic frequency (CF) and a tendency to decrease them for low CF sites; (3) the mean stimulus driven firing rates were not affected by either drug except for a decrease produced by quinine in AI; (4) changes in driven firing rate were positively correlated with changes in spontaneous firing rates. This suggests that tinnitus inducing agents selectively increase spontaneous firing rates in the extralemniscal pathway.

Acoustic Stimulation↗
PubMed1995

Interactive effects of fluoride and aluminum uptake and accumulation in bones of rabbits administered both agents in their drinking water.

Fluoride (F) and aluminum (Al), which are known to form a strong complex, are both present in finished drinking water. The effect of F and AI on one another's tissue accumulation was determined using adult male New Zealand white rabbits. Thirty-six rabbits (three per group) were given Purina Rabbit Chow and drinking water containing no F or AI, F alone (1, 4, or 50 ppm F as NaF), Al alone, (100 or 500 ppm Al as AlCl3), or a combination of F and Al, ad libitum for 10 wk. None of these treatments altered food intake or weight gain in these rabbits. However, rabbits treated with 1 ppm F and 500 ppm Al consumed significantly less water than control rabbits. The F accumulation in plasma, urine, incisors, and tibia was increased as the F addition to the drinking water increased within groups receiving a single concentration of Al. In contrast, F accumulation in plasma, urine, incisors, and tibia decreased as the Al concentration increased within groups receiving a single F concentration, indicative of decreased intestinal absorption. Importantly, Al levels in tibia were significantly increased by the addition of F to the drinking water, even in animals receiving no Al in their drinking water. The effect of F on Al accumulation in bone was confirmed by our evaluating Al levels in sterna harvested from rats treated with 0 or 79 ppm F (as NaF in the drinking water) in a study conducted by the National Toxicology Program (Bucher et al., 1991). Therefore, some of the osteotoxicity seemingly associated with high F levels in bone may be due to the accumulation of Al or an Al-F complex.

Aluminum↗
PubMed1981

The specificity of angiotensin II receptor binding in rat brain.

125I-angiotensin II (125I-AII) binding was examined in the hypothalamic-thalamic-septal-midbrain (HTSM) region of HLA-Wistar rats in the presence of CNS-active agents. Angiotensin I, II, and III and saralasin competed for 125 I-AII binding, whereas structurally unrelated peptides such as arginine and lysine vasopressin, oxytocin, LHRH, TRH, bradykinin, and substance P did not. In contrast, ACTH and neurotensin exhibited a weak, dose-dependent competition for 125 I-AII binding. The relative potencies of AII, AI, neurotensin and ACTH were 100:1:0.1:0.05, respectively. Neurotensin and ACTH competition was not additive with AII suggesting interaction at shared binding sites. Most importantly, a wide variety of other CNS active agents such as methyldopa, naloxone, catecholamines, clondidine, and reserpine, failed to inhibit 125 I-AII binding, thus further defining the specificity of the CNS AII receptor.

Adrenocorticotropic Hormone↗
PubMed2006

[The anti-respiratory syncytial virus effect of active compound of Glycyrrhiza GD4 in vitro].

OBJECTIVE: To study the effect on anti-respiratory syncytial virus of an active compound GD4 from Glycyrrhiza in vitro. METHODS: GD4 was extracted from Glycyrrhiza by hot water extraction, dichloromethane extraction and column chromatography. The CPE inhibition assay was used to test the antiviral activity of GD4 on RSV in Hela cells. RESULTS: GD4 was effective antiviral agent for RSV in a concentration-dependent manner and its median toxic concentration (TC50) and median effeicacious concentration (EC50) and treatment index (TI) was 0.23 mg/ml, 28.73 microg/ml and 8.0. 120 microg/ml GD4 exhibited inhibitory effect when added into cell culture for every 2h within 12h post-infection. GD4 didn't contain glycyrrhizic acid. CONCLUSION: The active compound of Glycyrrhiza (GD4) was an evident inhibitory effect on RSV.

Antiviral Agents↗
PubMed1996

Molecular mechanisms of fibrillogenesis and the protective role of amyloid P component: two possible avenues for therapy.

Amyloid deposits regress when the supply of fibril precursor proteins is sufficiently reduced, indicating that amyloid fibrils are degradable in vivo. Serum amyloid P component (SAP), a universal constituent of amyloid deposits, efficiently protects amyloid fibrils from proteolysis in vitro, and may contribute to persistence of amyloid in vivo. Drugs that prevent binding of SAP to amyloid fibrils in vivo should therefore promote regression of amyloid and we are actively seeking such agents. A complementary strategy is identification of critical molecular processes in fibrillogenesis as targets for pharmacological intervention. All amyloidogenic variants of apolipoprotein AI contain an additional positive charge in the N-terminal fibrillogenic region of the protein. This is unlikely to be a coincidence and should be informative about amyloidogenesis by this protein. The two amyloidogenic variants of human lysozyme, caused by the first natural mutations found in its gene, provide a particularly powerful model system because both the crystal structure and folding pathways of wild-type lysozyme are so well characterized. The amyloidogenic variant lysozymes have similar 3D crystal structures to the wild type, but are notably less thermostable. They unfold on heating, lose enzymic activity, and aggregate to form amyloid fibrils in vitro.

Amyloid↗
PubMed2005

Diclofenac, a nonsteroidal anti-inflammatory drug, activates the transient outward K+ current in rat cerebellar granule cells.

Diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), has been widely investigated in terms of its pharmacological action, but less is known about its direct effect on ion channels. Here, the effect of diclofenac on voltage-dependent transient outward K+ currents (I(A)) in cultured rat cerebellar granule cells was investigated using the whole-cell voltage-clamp technique. At concentrations of 10(-5)-10(-3) M, diclofenac reversibly increased the I(A) amplitude in a dose-dependent manner and significantly modulated the steady-state inactivation properties of the I(A) channels, but did not alter the steady-state activation properties. Furthermore, diclofenac treatment resulted in a slightly accelerated recovery from I(A) channel inactivation. Intracellular application of diclofenac could mimic the effects induced by extracellular application, although once the intracellular response reached a plateau, extracellular application of diclofenac could induce further increases in the current. These observations indicate that diclofenac might exert its effects on the channel protein at both the inner and outer sides of the cell membrane. Our data provide the first evidence that diclofenac is able to activate transient outward potassium channels in neurons. Although further work will be necessary to define the exact mechanism of diclofenac-induced I(A) channel activation, this study provides evidence that the nonsteroidal anti-inflammatory drug, diclofenac, may play a novel neuronal role that is worthy of future study.

Analysis of Variance↗
PubMed2005

Oral mizoribine pulse therapy for patients with steroid-resistant and frequently relapsing steroid-dependent nephrotic syndrome.

BACKGROUND: We investigated the efficacy of oral mizoribine pulse therapy (mizoribine-pulse) for cyclosporin (CyA)-dependent, steroid-resistant nephrotic syndrome (SRNS) and frequently relapsing, steroid-dependent nephrotic syndrome (FR-SDNS). METHODS: One child with CyA-dependent SRNS and eight children with CyA-dependent FR-SDNS were treated with mizoribine-pulse (daily dose: 10 mg/kg; maximum total dose 500 mg). We compared clinical manifestations before and after mizoribine-pulse, and studied the changes in serum mizoribine concentration in each patient on days when mizoribine was administered. RESULTS: Four patients had no subsequent relapses (responders). Two of the four responders discontinued prednisolone and CyA, the other two discontinued CyA. Although each of the five other patients (non-responders) experienced single subsequent relapses, the dosages of prednisolone and CyA after mizoribine-pulse were decreased significantly compared with before mizoribine-pulse. The peak blood concentration of mizoribine in the responders was higher than in the non-responders (3.6+/-0.9 vs 1.8+/-0.4 microg/ml). CONCLUSIONS: Mizoribine-pulse may be effective for some patients with CyA-dependent SRNS and FR-SDNS.

Administration, Oral↗
PubMed2003

Production of the signalling molecule, autoinducer-2, by Neisseria meningitidis: lack of evidence for a concerted transcriptional response.

Neisseria meningitidis is a Gram-negative bacterium which is an important causative agent of septicaemia and meningitis. LuxS has been shown to be involved in the biosynthesis of a quorum sensing molecule, autoinducer-2 (AI-2), known to play a role in virulence in Escherichia coli, as well as other bacteria. Evidence that serogroup B of N. meningitidis produces AI-2, along with the observation that a luxS mutant of this strain had attenuated virulence in an infant rat model of bacteraemia, led to further investigation of the role of this quorum sensing molecule in N. meningitidis. In this study, it is demonstrated that AI-2 is not involved in regulating growth of meningococci, either in culture or in contact with epithelial cells. Furthermore, transcriptional profiling using DNA microarrays shows an absence of the concerted regulation seen in other bacteria. Taken together, these data suggest that in N. meningitidis, AI-2 may be a metabolic by-product and not a cell-to-cell signalling molecule.

Animals↗
PubMed2006

Detection of live and antibiotic-killed bacteria by quantitative real-time PCR of specific fragments of rRNA.

Assessing bacterial viability by molecular markers might help accelerate the measurement of antibiotic-induced killing. This study investigated whether rRNA could be suitable for this purpose. Cultures of penicillin-susceptible and penicillin-tolerant (Tol1 mutant) Streptococcus gordonii were exposed to mechanistically different penicillin and levofloxacin. Bacterial survival was assessed by viable counts and compared to quantitative real-time PCR amplification of either the 16S rRNA genes or the 16S rRNA, following reverse transcription. Penicillin-susceptible S. gordonii lost > or =4 log(10) CFU/ml of viability over 48 h of penicillin treatment. In comparison, the Tol1 mutant lost < or =1 log(10) CFU/ml. Amplification of a 427-bp fragment of 16S rRNA genes yielded amplicons that increased proportionally to viable counts during bacterial growth but did not decrease during drug-induced killing. In contrast, the same 427-bp fragment amplified from 16S rRNA paralleled both bacterial growth and drug-induced killing. It also differentiated between penicillin-induced killing of the parent and the Tol1 mutant (> or =4 log(10) CFU/ml and < or =1 log(10) CFU/ml, respectively) and detected killing by mechanistically unrelated levofloxacin. Since large fragments of polynucleotides might be degraded faster than smaller fragments, the experiments were repeated by amplifying a 119-bp region internal to the original 427-bp fragment. The amount of 119-bp amplicons increased proportionally to viability during growth but remained stable during drug treatment. Thus, 16S rRNA was a marker of antibiotic-induced killing, but the size of the amplified fragment was critical for differentiation between live and dead bacteria.

Anti-Bacterial Agents↗
PubMed2004

Long term effect (more than five years) of intrathecal baclofen on impairment, disability, and quality of life in patients with severe spasticity of spinal origin.

OBJECTIVES: To evaluate long term change in impairment, disability, and health related functional status in patients with severe spasticity who received intrathecal baclofen. METHODS: A long term (more than five years) observational longitudinal follow up study assessing 21 patients who received intrathecal baclofen given by programmable pump. Patients had chronic disabling spasticity which did not respond to oral antispasmolytic agents. Clinical efficacy was assessed by the Ashworth scale and spasm score; disability by the expanded disability status scale (EDSS), ambulation index (AI), and incapacity status scale (ISS); and health related quality of life by the sickness impact profile (SIP) and the Hopkins symptom checklist (HSCL). RESULTS: Compared with pretreatment values, there was a significant improvement in clinical efficacy (Ashworth scale and spasm score, p<0.05) but a small but significant worsening of disability (EDSS, AI, and ISS, p<0.05). Comparing pretreatment with 26 weeks after pump implantation, a worsening was observed in disability (EDSS and ISS, p<0.05) and perceived health status (SIP, psychosocial dimension, p<0.05). CONCLUSIONS: Long term administration of intrathecal baclofen delivered by an implanted programmable pump resulted in improved clinical efficacy but not in improvement in disability or perceived health status.

Activities of Daily Living↗
PubMed2002

[Reversal of anti-apoptotic action by tetrandrine in human breast carcinoma multidrug-resistant MCF-7 cells].

OBJECTIVE: To study whether the anti-apoptotic action is reversed by tetrandrine in a combination with vincristine in human breast carcinoma MCF-7 multidrug-resistant cells. METHOD: Chromatin condensation was observed by co-staining of fluorescent dyes Hoechst 33342 and propidium iodide; and G1 sub-peak was detected by flow cytometry. Apoptotic cells were detected with TUNEL method. Cellular free ca2+ was determined with Fluo-3 staining method. RESULT: Two types of chromatin condensation were observed after the sensitive and drug-resistant MCF-7 cells were treated with an antitumor drug vincristine 5 mumol.L-1 for 24 h. The number of cell with chromatin condensation was obviously reduced in the drug-resistant cells treated with the same concentration of vincristine, as compared with the sensitive MCF-7 cells. The number of the apoptotic cells was increased by a combination of non-cytotoxic tetrandrine 20 mumol.L-1 and vincristine in both the sensitive and drug-resistant cells, which was confirmed with fluorescent indication and TUNEL method. The increment of introcellular free Ca2+ level in the cells treated with tetrandrine in a combination of vincristine was detected with Fluo-3 staining method. CONCLUSION: The anti-apoptotic action of human breast carcinoma MCF-7 cells can be effectively reversed by tetrandrine.

Alkaloids↗
PubMed2005

[Clinical study on treatment of fatty liver by shennong ganzhining].

OBJECTIVE: To observe the therapeutic effect and safety of Shennong Ganzhining (SG) in treating fatty liver. METHODS: One hundred and ninety patients with fatty liver were randomly divided into two groups. The 142 patients in the treated group received SG and the 48 in the control group received Zhibituo treatment for 3 months. The comprehensive therapeutic effect after treatment, symptoms, signs, liver function, blood lipids and blood viscosity, as well as iconographic parameters were observed. RESULTS: The total effective rate in the treated group was 80.98%, which was higher than that in the control group (75.00%), showing significant difference statistically (P < 0.05). Satisfactory effect was obtained in recovery of liver function, improvement of blood lipids, blood viscosity and iconographic parameters, no severe adverse reaction occurred. CONCLUSION: SG is obviously effective in treating fatty liver with favorable safety.

Adolescent↗
PubMed2005

Three new polymeric isopropenyl benzofurans from Ligularia stenocephala.

Three new polymeric isopropenyl benzofurans, 4-methyl-2,4-bis(5,6-dimethoxy-2-benzofuranyl)-1-pentene, stenocephalin A (1), 4,6-dimethyl-2,4,6-tri(5,6-dimethoxy-2-benzofuranyl)-1-heptene, stenocephalin B (2) and 4,6,8-trimethyl-2,4,6,8-tetra(5,6-dimethoxy-2-benzofuranyl)-1-nonene, stenocephalin C (3), together with seven known compounds (4-10) were isolated from the roots of Ligularia stenocephala. The structures of the new compounds were elucidated on the basis of spectral evidence, especially on 2D NMR. In addition, the cytotoxic activity and the anti-bacterial activity of compounds 2, 3, 5 and 6 were tested.

Alkenes↗
PubMed2005

[Determination of lead and cadmium contents in chicken granules and gourmet powder].

Through atomic absorption detector, the contents of Pb and Cd in chicken granules and gourmet powder were determined. From the result it was found that there are differing contents of pollutant elements, i. e. 0.00-10.00 microg x mL(-1) for Pb and 0.00-4.00 microg x mL(-1) for Cd, respectively. The relative standard deviations of Pb and Cd are 3.15% and 4.26%, respectively. At the same time, a recovery experiment for Pb and Cd in chicken granules and gourmet powder were performed, and the recoveries are 96.7%-102.1% for Pb and 91.9%-107.6% for Cd, respectively.

Animals↗
PubMed2005

Antihypertensive effect of total flavonoid fraction of Astragalus complanatus in hypertensive rats.

The purpose of the present study was to quantify the antihypertensive effect of the total flavonoid (TF), extracted from the seed of Astragalus complanatus R. Brown, and to observe its effect on the renin-angiotensin system (RAS) in both renal hypertensive rats (RHR) and spontaneously hypertensive rats (SHR). RHR were created by the two-kidney one clip (2K1C) method. Systolic blood pressure was measured in conscious rats by the tail-cuff method. Plasma angiotensin II (AngII) and plasma renin activity (PRA) were measured with radioimmunoassay at 60 min after drug administration. The effects of TF on cardiac hemodynamics were also recorded in anesthetized RHR and SHR. TF was given by oral administration in low dose (100 mg/kg) and high dose (200 mg/kg) respectively. Compared to pre-administration control, TF induced an obvious decrease in systolic blood pressure in conscious normotensive Wistar rat, RHR and SHR. In the three groups the systolic blood pressure reached the lowest value at 60 min after TF. TF also induced a significant decrease in blood pressure in anesthetized RHR and SHR. At 60 min after treatment of TF, mean arterial pressure in high dose group (200 mg/kg) was decreased by 17% in RHR and by 17% in SHR respectively (P < 0.01). The depressor effect of TF lasted for at least 60 min. Cardiac output, heart rate and +/- dp/dtmax did not change. Conversely, total peripheral resistance was significantly decreased. The decrease in plasma AngII was found in both RHR and SHR. On the contrary, PRA increased at the same time. These findings suggested that TF is effective in reducing blood pressure in both RHR and SHR. The antihypertensive action of TF was attributed to a decrease in TPR secondary to a decrease in plasma concentration of AngII caused by TF.

Angiotensin II↗