Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AI agents”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMedDate not supplied

Initial subsensitivity to anxiolytic treatments on conflict behavior in rats: parametric studies across drug classes.

In conflict paradigms, benzodiazepines (BZs) often exhibit maximal anticonflict effects only after three to four BZ exposures (anxiolytic initial subsensitivity; AIS). The present experiments examined 1) whether AIS occurs with non-BZ anxiolytics and 2) whether prior exposure to non-BZs prevents the occurrence of BZ AIS. Female rats were trained to stable responding levels on a repeated-measures punished drinking paradigm. In Experiment 1, dose-response curves for the effects of the BZs chlordiazepoxide and diazepam, the barbiturates (BBs) pentobarbital and amobarbital, and the non-BZ, non-BB agent carbamazepine were determined in five groups of rats (one group/drug); dose-response curves were determined on two occasions for each drug. There was an AIS with both BZs, with the anticonflict effect being significantly greater for dose-response determination #2. There was no AIS with the BBs (robust and dose-dependent increases in punished responding on both determinations) or with carbamazepine (weak anticonflict effect on both determinations). In Experiment 2, the rats from Experiment 1 received a single-dose challenge with chlordiazepoxide (10 mg/kg). This challenge resulted in a robust anticonflict effect in subjects with a history of repeated BZ treatment; in contrast, subjects with a history of repeated BB or carbamazepine treatment exhibited smaller anticonflict responses. These data suggest that 1) the AIS does not occur with non-BZ anxiolytics and 2) the BZ AIS cannot be prevented by repeated exposure to non-BZs.

Animals↗
PubMed2004

Response to fulvestrant in heavily pretreated postmenopausal women: a single-center experience.

Fulvestrant ('Faslodex') is a new estrogen receptor (ER) antagonist that has no agonist effects. It binds, blocks and accelerates degradation of the ER, leading to a complete abrogation of estrogen-sensitive gene transcription. In postmenopausal women with advanced breast cancer progressing on prior endocrine therapy, fulvestrant is at least as effective as the third-generation aromatase inhibitor (AI) anastrozole. In this single-center experience, 42 postmenopausal patients with metastatic breast cancer who had been heavily pretreated with prior endocrine therapy and chemotherapy were treated with fulvestrant. Prior endocrine therapies included selective ER modulators (including tamoxifen and toremifene), AIs, megestrol acetate, and high-dose estrogens. In total, eight patients (19%) achieved stable disease (SD) for > or =24 weeks, including two patients with SD for 2 years and one with SD for 14 months. Fulvestrant was well tolerated with the majority of adverse events related to the site of metastatic disease. These data demonstrate that fulvestrant is a well tolerated and effective endocrine therapy for postmenopausal women with metastatic breast cancer who have been heavily pretreated with prior therapies. The novel mechanism of action of fulvestrant reduces the likelihood of cross-resistance with other endocrine therapies and therefore this agent may be active in patients who have proved to be resistant to treatments such as tamoxifen or AIs. The use of fulvestrant earlier in the sequence of endocrine treatments may achieve better responses than observed in this heavily pretreated patient population.

Adult↗
PubMed2002

[Study on antiinflammatory effect of a compound TCM agent containing ant extractive in animal models].

OBJECTIVE: To study the antiinflammatory effect of a compound TCM (Traditional Chinese Medicine) agent on animal models. The agent contains ant extractive and a blent of three herbal products, herba epimedii, fructus cnidii, and fructus lycii. METHOD: Three animal models to induce experimental inflammation in rats, including carrageenin--induced paw edema, cotton-ball granuloma and adjuvant induced arthritis, were chosen to study the antiinflammatory effect of the TCM agent. RESULT: The TCM agent showed a marked inhibitory effect on edema induced by all three types of inflammation in rats, the inhibitory rate of the TCM agent at the dose of 0.20, 0.40 and 0.80 g.kg-1 in granuloma model bing over 25% at 1 hour post oral administration, and being 23.8%, 22.7%, 39.7% at 6 hour. In addition, the TCM agent also showed a significant preventive as well as therapeutic effect on adjuvant induced arthritis in rats, and improved the pathological changes of the animal joints with the induced arthritis. CONCLUSION: TCM agent has significant antiinflammatory effects on the three above mentioned animal models.

Animals↗
PubMed2005

Isoprenylated xanthones and flavonoids from Cudrania tricuspidata.

Further phytochemical investigation on the roots of Cudrania tricuspidata afforded a new isoprenylated xanthone, cudratricusxanthone I (1), two new isoprenylated flavanones, cudraflavanones C and D (2 and 3, resp.), and seven known compounds, 1,7-dihydroxy-3,6-dimethoxyxanthone (4), macluraxanthone C (5), cudraxanthones E, K, and L (6, 7, and 8, resp.), cudraflavanone A (9), and cudraflavone C (10). Their structures were identified by spectroscopic methods. Cudratricusxanthone H (12), macluraxanthone B (13), two xanthones previously isolated from this plant, and 5, showed significant inhibitory effects on four kinds of human digestive apparatus tumor cell lines (HCT-116, SMMC-7721, SGC-7901, and BGC-823) with IC50 values of 2.70-12.66 microM.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Self-assembled drug delivery systems. 1. Properties and in vitro/in vivo behavior of acyclovir self-assembled nanoparticles (SAN).

Self-assembled drug delivery systems (SADDS) were designed in the paper. They can be prepared from the amphiphilic conjugates of hydrophilic drugs and lipids through self-assembling into small-scale aggregates in aqueous media. The outstanding characteristic of SADDS is that they are nearly wholly composed of amphiphilic prodrugs. The self-assembled nanoparticles (SAN) as one of SADDS had been prepared from the lipid derivative of acyclovir (SGSA) in the previous paper. They were further studied on the properties and the in vitro/in vivo behavior in this paper. The SAN kept the physical state stable upon centrifugation or some additives including some inorganic salts, alkaline solutions, surfactants and liposomes except for HCl solution, CaCl(2) solution and animal plasma. Autoclave and bath heat for sterilization hardly influenced the SAN. However, gamma-irradiation strongly destroyed the structure of SAN and SGSA was degraded. SGSA in SAN showed good stability in weak acidic or neutral buffers although it was very sensitive to alkaline solutions and carboxylester enzymes, the half-lives (t(1/2)) of which in the buffer at pH 7.4, the alkaline solution at pH 12.0, pig liver carboxylester enzyme solution, rabbit plasma, and rabbit liver tissue homogenate were 495, 21, 4.7, 25 and 8.7 h, respectively. Compared with SGSA in a disordered state, the specific bilayer structures of SAN could protect SGSA from hydrolysis through hiding the sensitive ester bonds. The SAN showed hemolytic action because the amphiphilic SGSA could insert into rabbit erythrocyte membranes. Both the high concentration of SGSA in samples and the long incubation time improved hemolysis. No hemolysis was observed if the additional volume of the SAN was less than 10% of rabbit whole blood in spite of the high concentration of SGSA. Plasma proteins could interfere the interaction between the SAN and erythrocytes by binding the SAN. The in vitro antiviral activity of acyclovir SAN was limited possibly because of the weak hydrolysis of SGSA in Vero cells, and the SAN showed a little cell toxicity possible due to the amphiphilicity of SGSA. A macrophage cell line of QXMSC1 cells showed uptake of the SAN but not significantly. The SAN were rapidly removed from blood circulation after bolus iv administration to rabbits with the very short distribution t(1/2) (1.5 min) and the elimination t(1/2) (47 min). The SAN were mainly distributed in liver, spleen and lung after iv administration, and SGSA was eliminated slowly in these tissues (t(1/2), about 7 h). It would appear that the nanosized SAN were trapped by the mononuclear phagocyte system. SADDS including SAN combine prodrugs, molecular self-assembly with nanotechnology, and hopefully become novel drug delivery approaches.

Acyclovir↗
PubMedDate not supplied

[Pharmaceutical care program for pediatric patients receiving antiretroviral therapy].

OBJECTIVE: To present a pharmaceutical care program for pediatric patients receiving antiretroviral therapy. METHOD: In order to establish the pharmaceutical care procedure, papers published up to 2004 on the pharmaceutical care provided to patients receiving antiretroviral therapy were reviewed through a search in Medline and the journal Farmacia Hospitalaria. In addition, bibliographic references that can be systematically used to analyze the pharmacotherapy of each patient have been selected. RESULTS: The pharmaceutical care procedure is divided in three stages (data collection, analysis of the pharmacotherapeutic profile and resolution of the drug-related problems identified) that take place through a semi-structured type of interview. In order to systematize the role of the pharmacist, a table with information on antiretroviral drugs used in Pediatrics was created, as well as an information three-page leaflet and a data collection form. CONCLUSIONS: The program includes the goals of the pharmaceutical care process as defined in the recommendations of GESIDA-SEFH-National AIDS Plan 2004 and systematizes the proposed intervention strategies, in an attempt to provide the patient and the caregiver with the information required for an optimum management, in the most comprehensive way and tailored to their individual characteristics.

Anti-Retroviral Agents↗
PubMed2006

Suppression of Fas-mediated apoptosis of keratinocyte cells by chikusetsusaponins isolated from the roots of Panax japonicus.

Fas-mediated apoptotic cell death of a human keratinocyte cell line, HaCaT cells, and of a murine keratinocyte cell line, Pam212 cells, was suppressed by pre-treatment with a methanol extract from the roots of Panax japonicus C.A. Meyer. Activity-guided fractionation led to the isolation of chikusetsusaponins IV, IVa, V and polysciasaponin P5 as the active ingredients. Of these compounds, chikusetsusaponin IV, was most active when applied at a concentration of 12.5 microg/mL. The intracellular hallmark events of apoptosis such as DNA fragmentation and chromatin condensation were significantly reduced by the treatment with chikusetsusaponin IV. The apoptotic cell death of Jurkat cells was also suppressed by treatment with the active saponins. These results suggest that the use of chikusetsusaponins IV, IVa, V, polysciasaponin P5, or a crude extract of P. japonicus containing these saponins is expected to relieve cutaneous symptoms caused by excessive apoptotic cell death in the skin through the Fas/FasL pathway.

Animals↗
PubMed2003

Chromatin-mediated regulation of nucleolar structure and RNA Pol I localization by TOR.

The target of rapamycin (TOR) protein is a conserved regulator of ribosome biogenesis, an important process for cell growth and proliferation. However, how TOR is involved remains poorly understood. In this study, we find that rapamycin and nutrient starvation, conditions inhibiting TOR, lead to significant nucleolar size reduction in both yeast and mammalian cells. In yeast, this morphological change is accompanied by release of RNA polymerase I (Pol I) from the nucleolus and inhibition of ribosomal DNA (rDNA) transcription. We also present evidence that TOR regulates association of Rpd3-Sin3 histone deacetylase (HDAC) with rDNA chromatin, leading to site-specific deacetylation of histone H4. Moreover, histone H4 hypoacetylation mutations cause nucleolar size reduction and Pol I delocalization, while rpd3Delta and histone H4 hyperacetylation mutations block the nucleolar changes as a result of TOR inhibition. Taken together, our results suggest a chromatin-mediated mechanism by which TOR modulates nucleolar structure, RNA Pol I localization and rRNA gene expression in response to nutrient availability.

Antifungal Agents↗
PubMed1996

A foveal-sparing pattern of cytomegalovirus retinitis in the acquired immunodeficiency syndrome.

PURPOSE: We describe the clinical course of 12 eyes of 10 patients in whom recurrent cytomegalovirus (CMV) retinitis exhibited a foveal-sparing pattern. METHODS: We retrospectively reviewed the case records and photographic charts of 10 patients (12 eyes) with the acquired immunodeficiency syndrome (AIDS), in whom recurrent CMV retinitis exhibited a foveal-sparing pattern within 1500 mm of the foveola. RESULTS: The site of primary retinitis was temporal in 10 eyes of nine patients in whom it was known. The median number of recurrences up to the observation of foveal-sparing retinitis was two (range one to eight), and five patients had active CMV retinitis despite treatment for at least two continuous months. Once established, the median rate of progression in a non-foveal vector was 2.3 times faster than toward the fovea, and the median time to reduction in acuity to < 6/30 (or death) was 11 to 14 weeks. Three eyes of three patients retained 6/30 or better acuity up to death. Foveal CMV retinitis ultimately reduced acuity to < 6/30 in five eyes. Six eyes suffered retinal detachment, involving the fovea in five, and being the primary reason for acuity of < 6/30 in four. Four patients suffered dose-limiting toxicity. CONCLUSION: Foveal-sparing CMV retinitis arises in patients with recurrent CMV retinitis resistant to treatment ('clinically resistant'), particularly that which has arisen temporally. Despite its foveolar proximity, and ultimate significant loss of function, the pattern of progression allows for preservation of useful foveal vision for longer periods than would have been expected.

AIDS-Related Opportunistic Infections↗
PubMed2003

Increased renal medullary H2O2 leads to hypertension.

We have recently reported that exaggerated oxidative stress in the renal medulla due to superoxide dismutase inhibition resulted in a reduction of renal medullary blood flow and sustained hypertension. The present study tested the hypothesis that selective scavenging of O2*- in the renal medulla would prevent hypertension associated with this exaggerated oxidative stress. An indwelling, aortic catheter was implanted in nonnephrectomized Sprague-Dawley rats for daily measurement of arterial blood pressure, and a renal medullary interstitial catheter was implanted for continuous delivery of the superoxide dismutase inhibitor diethyldithiocarbamic acid (DETC, 7.5 mg x kg(-1) x d(-1)) and a chemical superoxide dismutase mimetic, 4-hydroxytetramethyl piperidine-1-oxyl (TEMPOL, 10 mg. kg-1. d-1). Renal medullary interstitial infusion of TEMPOL completely blocked DETC-induced accumulation of O2*- in the renal medulla, as measured by the conversion rate of dihydroethidium to ethidium in the dialysate and by urinary excretion of 8-isoprostanes. However, TEMPOL infusion failed to prevent DETC-induced hypertension, unless catalase (5 mg x kg(-1) d(-1)) was coinfused. Direct infusion of H2O2 into the renal medulla resulted in increases of mean arterial pressure from 115+/-2.5 to 131+/-2.1 mm Hg, which was similar to that observed in rats receiving the medullary infusion of both TEMPOL and DETC. The results indicate that sufficient catalase activity in the renal medulla is a prerequisite for the antihypertensive action of TEMPOL and that accumulated H2O2 in the renal medulla associated with exaggerated oxidative stress might have a hypertensive consequence.

Animals↗
PubMed2004

Connexin 43 downregulation and dephosphorylation in nonischemic heart failure is associated with enhanced colocalized protein phosphatase type 2A.

In nonischemic heart failure (HF), ventricular tachycardia initiates by a nonreentrant mechanism, but there is altered conduction (that could lead to re-entry) that could arise from changes in gap junctional proteins, especially connexin43 (Cx43). We studied Cx43 expression and phosphorylation state in the left ventricle (LV) from an arrhythmogenic rabbit model of nonischemic HF and from patients with HF attributable to idiopathic dilated cardiomyopathy. We also investigated the role of protein phosphatases that dephosphorylate Cx43--PP1 and PP2A. In HF rabbit LV, Cx43 mRNA and total protein were decreased by 29% and 34%, respectively (P<0.05 and P<0.001). In controls, Cx43 was primarily in the phosphorylated state, but with HF there was a 64% increase in nonphosphorylated Cx43 (Cx43-NP, normalized to total Cx43; P<0.05). Similar results were noted in HF rabbit myocytes (P<0.05) and in human idiopathic dilated cardiomyopathy LV (P<0.05). We found that PP1 and PP2A colocalized with Cx43 in rabbit LV. With HF, the level of colocalized PP2A increased >2.5-fold (P<0.002), whereas colocalized PP1 was unchanged. We also found intercellular coupling (assessed by Lucifer Yellow dye transfer) was markedly reduced in HF. However, okadaic acid (10 nmol/L) reduced the amount of Cx43-NP and significantly improved cell coupling in HF. Thus, in nonischemic HF in rabbits and humans, there is a decrease in both Cx43 expression and phosphorylation that contributes to uncoupling. Increased levels of PP2A that colocalize with Cx43 can underlie enhanced levels of Cx43-NP in HF. Modulation of Cx43 phosphorylation may be a potential therapeutic target to improve conduction in HF.

Animals↗
PubMed2004

Photocatalytic killing effect of TiO2 nanoparticles on Ls-174-t human colon carcinoma cells.

AIM: To investigate the photocatalytic killing effect of photoexcited TiO(2) nanoparticles on human colon carcinoma cell line (Ls-174-t) and to study the mechanism underlying the action of photoexcited TiO(2) nanoparticles on malignant cells. METHODS: Ls-174-t human colon carcinoma cells were cultured in RPMI 1640 medium supplemented with 199 mL/L calf serum in a humidified incubator with an atmosphere of 50 mL/L CO(2) at 37 degrees C. Viable cells in the samples were measured by using the MTT method. A GGZ-300 W high pressure Hg lamp with a maximum ultraviolet-A (UVA, 320-400 nm) irradiation peak at 365 nm was used as light source in the photocatalytic killing test. RESULTS: The photocatalytic killing of Ls-174-t cells was carried out in vitro with TiO(2) nanoparticles. The killing effect was weak by using UVA irradiation without TiO(2) nanoparticles. In our studies, the photocatalytic killing effect was correlated with the concentration of TiO(2) and illumination time. Once TiO(2) was added, Ls-174-t cells were killed at a much higher rate. In the presence of 1 000 microg/mL TiO(2), 44% of cells were killed after 10 min of UVA irradiation, and 88% of cells were killed after 30 min of UVA irradiation. CONCLUSION: When the concentration of TiO(2) is below 200 microg/mL, the photocatalytic killing effect on human colon carcinoma cells is almost the same as that of UVA irradiation alone. When the concentration of TiO(2) is above 200 microg/mL, the remarkable killing effect of photoexcited TiO(2) nanoparticles can be found.

Antineoplastic Agents↗
PubMed2002

[Recombinant virus assay: a rapid assay for assessment of drug susceptibility of human immunodeficiency virus type 1 isolates].

OBJECTIVE: To establish a rapid assay for assessment of drug susceptibility of human immunodeficiency virus type 1 isolates (Recombinant virus assay). METHODS: This procedure allows the generation of viable virus with SI phenotype by homologous recombination of a RT-PCR-derived pool of reverse transcriptase (RT) coding sequences into an RT-deleted, noninfectious proviral clone, pHIV delta RTBstE II. Then the drug susceptibility of recombinant virus to RT inhibitors can be assessed in the Hela CD4+ plaque reduction assays. RESULTS: Analysis of 7 HIV strains with SI or NSI phenotype showed that recombinant viruses accurately exhibited the same genotype as that of the original HIV1 isolates. The results of drug susceptibilities of HIV1 isolate got by recombinant virus assay were the same as that by standardized peripheral blood mononuclear cell culture assay. CONCLUSION: Recombinant virus assay is a rapid and accurate method to assess the drug sensitivity of HIV1 isolates with SI or NSI phenotype.

Antiviral Agents↗
PubMed2005

[Antioxidant and anti-inflammatory effects of cyanidin from cherries on rat adjuvant-induced arthritis].

OBJECTIVE: To assess the possible antioxidant and anti-inflammatory activity of cyanidin from cherries on adjuvant induced arthritis (AA) in SD rats. METHOD: Arthritis was induced by the complete Freud's adjuvant in male Sprague Dauley rats and assessed based on paw swelling. Rats were randomly divided into normal group (NM), adjuvant arthritis group (AA) and three cyanidin-treated groups in high dosage (HA), middle dosage (MA), and low dosage (LA). The morphological changes in the hind limbs were conducted under a light microscope. We detected glutathione (GSH) in whole blood and malonaldehyde (MDA), superoxide dismutase (SOD), total antioxidative capacity (T-AOC) activity in serum by special kits to assess the antioxidant effects of cyanidin on AA. Moreover, the prostaglandin E2 (PGE2) levels in paw tissues were determined by radioimmunoassay and TNF-alpha levels in serum were determined using ELISA kits specific for rat. RESULT: The cyanidin could protect against the paws swelling in AA rats. From the day 14 after AA induction, the swellings of the cyanidin treated groups at high dosage and low dosage were significantly reduced compared with the model group (P < 0.05, 0.01). Histological examination of sections through the hind limbs revealed alleviation of inflammatory reaction in the joint after the treatment. The cyanidin at high and low dosage could increase the GSH, SOD activity and T-AOC levels in whole blood or serums and decrease MDA in AA rats (P < 0.01). The cyanidin could decrease the PGE2 levels in paw tissues and the TNF-alpha levels in serum at high and low dosages (P < 0.01). CONCLUSION: The cyanidin could protect against the paws swelling in AA rats, and alleviate the inflammatory reaction in the joint, and the mechanism might be via the increase activity of GSH, SOD and T-AOC that improve the total antioxidative capacity and scavenge the free radicals, perhaps as a result of that the levels of the PGE2 in paw tissues and TNF-alpha contents in serum were decreased. The results suggest that the cyanidin from cherries could be one of the potential candidates for the alleviation of arthritis.

Animals↗