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 667 records · Page 37Linked to original sources
PubMed1997

[Effect of Helicobacter pylori on gastric epithelial apoptosis].

To investigate the mechanisms by which Helicobacter pylori (Hp) induces gastric mucosal damage, gastric epithelial apoptotic index (AI) of normal gastric mucosa and Hp positive gastritis before and after anti-Hp treatment was studied with the method of terminal transferase mediated dUTP nick end labeling. The results showed that AI in Hp positive gastritis was higher than that in normal mucosa (P < 0.001). After the eradication of Hp, AI fell significantly to the normal level (P < 0.001). AI in persisting Hp positive gastritis had no statistically significant decrease after the anti-Hp treatment. There was no correlation between AI and the severity of gastritis. These results indicated that Hp could induce gastric epithelial apoptosis, which may be an important mechanism involved in gastric mucosal damage.

Adult↗
PubMed2003

A contribution to examination of propidium iodide and annexin V plasma cells indices in multiple myeloma.

The aim of this study was a contemporaneous measurement and a mutual comparison of plasma cells proliferative activity and grade of apoptosis in patients with monoclonal gammopathy of undetermined significance (MGUS) and various phases of MM i.e. smoldering (SMM), stable/plateau and active (progression/relapse) forms of this disease. The analyzed group of 197 patients consisted of 30 MGUS, 21 SMM, 82 patients examined at the time of MM diagnosis and 64 patients analyzed during various phases of the disease after previous chemotherapy. Plasma cell proliferative activity was measured by means of a propidium iodide index (PC-PI) examined by flow cytometry using a DNA/CD138 double staining technique. For detection of plasma cells entering apoptosis (PC-AI) flow cytometry method with annexin V FITC and MoAb CD138 was used. The individuals with MGUS, SMM and stable/plateau form of MM had overall low levels of PC-PI (M-1.8, 1.7% and 2.1%) and relatively high levels of PC-AI (M-9.1, 10.8 and 9.0%). The correlation between PC-PI and PC-AI was in all the groups mutually highly statistically significant (p=0.000). Analysis of plasma cells proliferative activity (PC-PI) was statistically significant in comparison of MGUS or SMM and versus: patients examined at the time of MM diagnosis (p=0.018 or 0.016); patients evaluated during various phases of MM after previous chemotherapy (p=0.021 or 0.019); stable/plateau MM phase in the cohort of all patients (p=0.017 or 0.040); in the plateau phase after chemotherapy (p=0.008 or 0.024) but insignificant in comparison of MGUS and SMM and with the stable group examined at the time of MM diagnosis. Analysis of the apoptotic process revealed significant differences when comparing PC-AI of SMM but not MGUS group versus all cohort of stable/plateau MM patients (p=0.045); there were also insignificant differences in comparison of MGUS and SMM groupsand versus the stable form of MM measured at the time of MM diagnosis or plateau phase after chemotherapy. There was observed a statistically significant difference in the PC-AI in comparison of SMM group versus group of all patients examined at the time of MM diagnosis (p=0.001) or in various phases of this disease (p=0.015) and the group of MGUS patients compared with patients evaluated at the time of MM diagnosis (p=0.03). Very significant statistical differences of plasma cell proliferative (PC-PI) and apoptotic (PC-AI) activity were found when comparing the levels of both the indices of MGUS, SMM and stable/plateau MM group versus the active (progression/relapse) form of MM marked by a higher level of PC-PI (3.2%, p=0.000) and PC-AI (4.8%, p=0.000) in the whole cohort of MM patients, but also in comparison with both the active forms at the time of MM diagnosis or active forms evaluated during various phases of the disease after chemotherapy. Highly significant inverse relationship between PC-PI versus PC-AI was also revealed in the group of patients in the active (progression/relapse) phase of MM (p=0.000). These results revealed importance of measurement not only of proliferative but also of apoptotic plasma cells indices for a complex evaluation of the cells kinetics of plasma cells compartments in patients with MGUS or MM. This study confirmed the initial hypothesis of a common 'inverse relationship between the proliferative (PC-PI) and the apoptosis activity (PC-AI) in plasma cells compartments in patients with MGUS, smoldering, stable/plateau and active (progression/ relapse) forms of MM'.

Annexin A5↗
PubMed2006

[TRAIL impacts in growth and apoptosis of human ovarian carcinoma cell line SKOV3].

OBJECTIVE: To investigate the effect of TRAIL on growth and apoptosis of ovarian carcinoma cell line SKOV3. METHODS: The effects of TRAIL alone and/or associating with DDP to treat on SKOV3 cells growth inhibition were measured by MTT assay, and the changes of DR4 and DR5 mRNA were detected by RT-PCR technique. The cell cycle and apoptosis index were analyzed by technique of Flow Cytometry (FCM). RESULTS: The soluble TRAIL protein had the inhibiting effect on the growth SKOV3 cells. The DDP increased the ability of TRAIL to SKOV3 cell growth inhibition. The apoptotic indexes (AI) of SKOV3 cells detected by FCM were 5.9%, 13.4% and 39.5% for control group, TRAIL group and TRAIL plus DDP group, respectively. The DDP increased the DR5 expressing in SKOV3 cells by 1.95 folds than control group and by 1.54 times for the DR4 expressing than the control group (P < 0.05). CONCLUSIONS: The soluble TRAIL has the effect on inhibiting the growth of SKOV3 cells. The combination use of TRAIL and DDP increases significantly the growth-inhibiting ratio to SKOV3 cells. The AI of SKOV3 cell is raised after TRAIL intervening in. The DDP can increase the expressions of DR4 and DR5 in SKOV3 cells.

Antineoplastic Agents↗
PubMed2004

Role of fibric acid derivatives in the management of risk factors for coronary heart disease.

Although elevated low-density lipoprotein (LDL)-cholesterol is a well established coronary heart disease (CHD) risk factor, the ability to adequately discriminate high-risk individuals by this risk factor alone is limited and other metabolic risk variables are known to modulate CHD risk. For instance, it has been reported that the cluster of metabolic disturbances observed among individuals with abdominal obesity, the so-called metabolic syndrome, is associated with a substantially increased risk of CHD. Among the features of the dyslipidaemic profile observed in these individuals, the high triglyceride-low high-density lipoprotein (HDL)-cholesterol dyslipidaemia is predictive of an elevated risk of CHD. Fibric acid derivatives (fibrates) have been used in clinical practice for more than 2 decades as a class of agents known to decrease triglyceride levels while substantially increasing HDL-cholesterol levels, with a limited but significant additional lowering effect on LDL-cholesterol levels. Although the clinical benefits of HMG-CoA reductase inhibitors (statins) have been well documented by primary and secondary prevention trials that justify their widespread use, it was not until the publication of the VA-HIT (Veterans Affairs High-Density Lipoprotein Intervention Trial) that the relevance of identifying HDL-cholesterol as a therapeutic target to reduce the risk of recurrent CHD events was finally confirmed. The clinical benefits of fibrate therapy are especially important in the subpopulation of patients with low HDL-cholesterol levels with the metabolic syndrome, particularly in patients with type 2 diabetes mellitus or in abdominally obese, hyperinsulinaemic patients. Evidence also suggests that there is a 'fibrate effect' that mediates the reduction in CHD risk beyond the favourable impact of these agents on HDL-cholesterol levels. This last notion is consistent with the pleiotropic effects of fibrates which are known to be related to their mechanisms of action. Through peroxisome proliferator-activated alpha-receptors, fibrates have a significant impact on the synthesis of several apolipoproteins (apo) and enzymes of lipoprotein metabolism as well as on the expression of several genes involved in fibrinolysis and inflammation. Fibrate therapy has been reported to decrease apo CIII levels (a powerful inhibitor of lipoprotein lipase) and increase apo AI levels, as well as to increase lipoprotein lipase activity. Such changes contribute to improve the catabolism of triglyceride-rich lipoproteins, leading to a substantial increase in HDL-cholesterol levels accompanied by a shift in the size and density of LDL particles (from small, dense LDL particles to larger, more buoyant cholesteryl ester-rich LDL). It is proposed that some of these pleiotropic effects could explain some of the clinical benefits of fibrate therapy beyond its HDL-raising properties, particularly among patients with abdominal obesity, hyperinsulinaemia or type 2 diabetes with both low HDL- and low/normal LDL-cholesterol levels.

Anticholesteremic Agents↗
PubMed1992

Effect of a novel series of macrocyclic hypolipidemic agents on plasma lipid and lipoprotein levels of four non-primate species.

The ansamycins are structurally novel hypolipidemic agents derived from rifampicin, but lacking antibacterial activity. Oral or intravenous administration resulted in rapid lowering of plasma cholesterol in rats, hamsters, guinea pigs and dogs. In the chow-fed rat, three related compounds (CGP 43371, CGS 23810 and CGS 24565) exhibited ED50 values of 13.7, 3.1 and 0.18 mg/kg, respectively. A feature common to the lipid lowering documented in these four species was the concomitant reduction of low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol. In the chow-fed rat, however, apolipoprotein AI (apo AI) levels were much less affected than were those of HDL cholesterol. CGP 43371 at 3 and 10 mg/kg, lowered HDL cholesterol by 20% and 39%, respectively, whereas plasma apo AI was reduced by only 1% and 12%. Similarly, in lipoprotein fractions separated by ultracentrifugation, apo AI was unchanged in the d = 1.019-1.21 g/ml fraction after treatment with 3 or 10 mg/kg of CGP 43371, but HDL cholesterol was reduced 12% and 26% in this fraction at the two dose levels. Plasma and lipoprotein apo B levels, on the other hand, were reduced to a level equivalent to that of the reduction in cholesterol. The ansamycins thus represent a new structural series which may possess a novel mechanism of action as well, involving differential effects on HDL cholesterol and protein.

Animals↗
PubMed2004

Neuroprotective effect of wogonin: potential roles of inflammatory cytokines.

Wogonin (5,7-dihydroxy-8-methoxyflavone), an active component originated from the root of Scutellaria baicalensis Georgi, has been reported to possess antioxidant and anti-inflammatory properties. In this study, we investigated the neuroprotective effect of wogonin in a focal cerebral ischemia rat model. Wogonin markedly reduced the infarct volume after 2 h middle cerebral artery occlusion followed by 22 h reperfusion. Wogonin decreased the production of nitric oxide and inflammatory cytokines such as TNF-alpha and IL-6 in lipopolisaccharide-stimulated microglial cells. While wogonin reduced the activity of NF-kappaB, it did not change the activity of mitogen-activated protein kinases family members, p38, ERK and JNK. The lipopolisaccharide-stimulated production of NO and cytokines was significantly blocked by various kinds of NF-kappaB inhibitors such as N-acetyl cysteine, pyrrolidinedithiocarbamate and MG-132. The data may indicate that wogonin has neuroprotective effect by preventing the overactivation of microglial cells, possibly by inactivating NF-kappaB signaling pathway.

Animals↗
PubMed2004

Epstein-Barr virus-associated hemophagocytic syndrome in a patient with lupus nephritis.

Hemophagocytic syndrome (HPS) is an unusual but severe illness associated with a variety of infections, as well as genetic, malignant tumors, and autoimmune diseases. We report an 11-year-old girl with systemic lupus erythematosus and nephritis who developed HPS associated with Epstein-Barr virus reactivation. In our patient, the onset of reactive HPS might be related to immunosuppressive treatment during the course of lupus nephritis.

Child↗
PubMed1994

Structural changes of high-density-lipoprotein apolipoproteins following incubation with human polymorphonuclear cells.

Based on the analogy in mechanisms and events between the pathogenesis of atherosclerosis and the inflammatory reaction, we investigated the impact of human polymorphonuclear leukocyte (PMN) degranulation and oxidative process on high-density-lipoprotein (HDL) structure. HDL were incubated (37 degrees C) with PMN at a physiological ratio (370 nmol cholesterol-HDL/ml with 2 x 10(6) PMN/ml) for 15, 30 and 60 min with or without stimulating agent. PMN activation was assessed by measurement of superoxide anion generation and elastase production, which both reached peak concentration at 15 min. HDL apolipoproteins (apo) analysed by immunoblotting after SDS/PAGE and electrofocusing evidenced the following modifications: (a) a slow hydrolysis of apo AII and apo Cs; (b) a rapid hydrolysis of apo E; (c) a change in apo AI isoform distribution with an increase in the most acidic isoform (AI-2) at the expense of a less acidic form (AI-1); (d) a shift of the major apo AII isoform into two more basic forms. In contrast, no quantifiable lipid modification nor lipid oxidation, assessed by thiobarbituric-acid-reactive substances (TBARS) were noted. Despite a lack of variation of TBARS, a decrease in HDL vitamin E content by 80% was observed. Since this decrease was prevented by addition of superoxide dismutase in the medium, we concluded the occurrence of an oxidative process affecting HDL. Experiments with proteolytic inhibitors showed that elastase caused the proteolytic cleavage of apolipoprotein E, AII and Cs. In contrast, apo AI modification might involve both oxidative and proteolytic processes.

Amino Acid Sequence↗
PubMed2005

Genetic polymorphisms of ATP-binding cassette transporters ABCB1 and ABCG2: therapeutic implications.

Pharmacogenomics, the study of the influence of genetic factors on drug action, is increasingly important for predicting pharmacokinetics profiles and/or adverse reactions to drugs. Drug transporters, as well as drug metabolism play pivotal roles in determining the pharmacokinetic profiles of drugs and their overall pharmacological effects. There is an increasing number of reports addressing genetic polymorphisms of drug transporters. However, information regarding the functional impact of genetic polymorphisms in drug transporter genes is still limited. Detailed functional analysis in vitro may provide clear insight into the biochemical and therapeutic significance of genetic polymorphisms. This review addresses functional aspects of the genetic polymorphisms of human ATP-binding cassette transporters, ABCB1 and ABCG2, which are critically involved in the pharmacokinetics of drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Experimental study of anti-tumor effects of polysaccharides from Angelica sinensis.

AIM: To investigate the in vivo anti-tumor effects of total polysaccharide (AP-0) isolated from Angelica sinensis (Oliv.) Diels (Danggui) on mice and the in vitro inhibitory effects of AP-0 and the sub-constituents (AP-1, AP-2 and AP-3) separated from AP-0 on invasion and metastasis of human hepatocellular carcinoma. METHODS: Three kinds of murine tumor models in vivo, sarcoma 180 (S180), leukemia L1210 and Ehrlich ascitic cancer (EAC) were employed to investigate the anti-tumor effects of AP-0. For each kind of tumor model, three experimental groups were respectively given AP-0 at doses of 30, 100 and 300 mg/kg by ip once a day for 10 days. Positive control groups were respectively given Cy at a dose of 30 mg/kg for S180 and leukemia L1210, and 5-FU at a dose of 20 mg/kg for EAC. On d 11, mice bearing S180 were sacrificed and the masses of tumors, spleens and thymus weighed. The average living days of mice bearing EAC and of mice bearing L1210 were observed, and the rates of life prolongation of each treatment were calculated, respectively. The inhibitory effects of APs on hepatoma invasion and metastasis in vitro were investigated by employing human hepatocellular carcinoma cell line (HHCC) with the Matrigel invasion chamber, adhesion to extracellular matrix and chemotatic migration tests, respectively. RESULTS: AP-0 had no obviously inhibitory effect on the growth of S180, but it could significantly decrease the thymus weights of the mice bearing S180. AP-0 could significantly reduce the production of ascitic liquids and prolong the life of mice bearing EAC. AP-0 could also increase the survival time of mice bearing L1210. AP-0 and AP-2 had significantly inhibitory effects on the invasion of HHCC into the Matrigel reconstituted basement membrane with the inhibitory rates of 56.4 % and 68.3 %, respectively. AP-0, AP-1, AP-2 and AP-3 could influence the adhesion of HHCC to extracellular matrix proteins (Matrigel and fibronectin) at different degrees, among them only AP-3 had significant blocking effect on the adhesion of HHCC to fibronectin with an inhibitory rate of 30.3 %. AP-0, AP-1 and AP-3 could partially inhibit the chemotactic migration abilities of HHCC. CONCLUSION: The experimental findings suggest that the total polysaccharide of Angelica sinensis (Oliv.) Diels (Chinese Danggui) possesses anti-tumor effects on experimental tumor models in vivo and inhibitory effects on invasion and metastasis of hepatocellular carcinoma cells in vitro.

Angelica sinensis↗
PubMed2006

[Preparation of puerarin solid self-microemulsion].

OBJECTIVE: To prepare puerarin solid self-microemulsifying drug delivery system (SMEDDS). METHODS: Pseudo-ternary phase diagram was used to select the formula of microemulsion. The self-microemulsification efficiency was assessed, such as viscosity, conductance, refraction, zeta potential, size ditribution, dissolution were investigated. Puerarin were determined by UV to calculate the cumulative release at different time. RESULTS: The optimum formulation of puerarin solid self-microemulsifying drug delivery system the consisted of puerarin-Tween 800 glycerinum-ethyl oleate-water-Gum Acacia-manicol at weight ratio of 1.7: 16. 6: 16. 6: 16. 6 : 1.3: 4.0: 39.9: 19.9; Average particle diameter was 30 nm; The dissolution was 94.29% at 10 min. CONCLUSION: Stability of puerarin solid self-microemulsion drug delvery system is good, potent in improving the dissolution of puerarin.

Biological Availability↗
PubMed2001

[Pharmacological effects of a thiazolidinedione derivative, pioglitazone].

Pioglitazone, a thiazolidinedione derivative, was developed from our basic research on diabetic animal models and our chemical research on lipid-lowering agents. In clinical studies, pioglitazone at doses of 15-45 mg/man/day produced 1.0-1.6% reduction in HbA1c for 6 months. Moreover, pioglitazone produced about 14% reduction in plasma triglyceride levels and 4-11% increase in HDL-cholesterol(HDL-C) levels without the significant changes in total cholesterol and LDL-C levels. Although the exact molecular mechanism of reducing insulin resistance still remains obscure, pioglitazone normalizes abnormalities in the cellular insulin signal transduction. This effect seems to be due to the inhibitory action of pioglitazone on TNF-alpha production, which is one of the factors responsible for insulin resistance. Pioglitazone is a potent agonist for the peroxisome proliferator activated receptor(PPAR)-gamma, that is related to differentiation of adipocytes, and the relationship between TNF-alpha production and PPAR-gamma has been reported. Therefore, the agonistic activity of pioglitazone on PPAR-gamma may be involved in the mechanism for reducing insulin resistance. Recently, it was demonstrated that pioglitazone is also an agonist of PPAR-alpha, which plays a central role in lipid metabolism through enhancing the synthesis of apo AI, apo AII and reverse cholesterol transporters, such as fatty acid transporter molecules, and SR-B1 and ABCA1 reverse cholesterol transport receptors. Therefore, these findings suggest that pioglitazone has a benefit for prevention of both diabetic micro-angiopathy and macro-angiopathy.

Animals↗
PubMed2005

Discovery of a novel small molecule, 1-ethoxy-3-(3,4-methylenedioxyphenyl)-2-propanol, that induces apoptosis in A549 human lung cancer cells.

A novel small molecule, 1-ethoxy-3-(3,4-methylenedioxyphenyl)-2-propanol (EOD), was synthesized in our laboratory. Previously, we reported pharmacological properties of EOD, triggering apoptosis in Human umbilical vein endothelial cells (HUVECs). Here, we further investigated the effects of EOD on the growth of A549 human lung cancer cells. EOD treatment induced apoptosis in A549 cells via up-regulating the expression of P53 protein, blocking cell cycle partly at G1 phase, and ultimately activating caspase-3. In contrast, caspase-8 might be irrelevant to EOD-triggered apoptosis. This study indicated that EOD might be a potential chemopreventive agent for lung cancer. The work would encourage us to add more novel compounds to our 'library' of small molecules derived through modern synthetic organic chemistry, and would drive us to determine the proteins that the compounds target.

Apoptosis↗
PubMed2004

Recent advances in endocrine therapy for postmenopausal women with early breast cancer: implications for treatment and prevention.

BACKGROUND: In the treatment of advanced breast cancer, third-generation aromatase inhibitors (AIs) have shown superior efficacy and tolerability compared with tamoxifen and megestrol acetate, the previous standard endocrine therapies in the first- and second-line settings, respectively. AIs are now being assessed in the adjuvant and prevention settings. DESIGN: Literature review (PubMed search). RESULTS: Tamoxifen is currently the only endocrine option available for adjuvant therapy and chemoprevention in postmenopausal women. However, results from the ATAC ('Arimidex', Tamoxifen, Alone or in Combination) trial have shown anastrozole to be more effective than tamoxifen as adjuvant therapy for postmenopausal women with hormone-responsive early breast cancer. Other third-generation AIs, including letrozole and exemestane, are also being investigated as adjuvant therapies. In the chemoprevention setting, tamoxifen is the only available endocrine option for women at high risk of breast cancer but, given that these are healthy subjects, is associated with an unacceptable rate of adverse events. Raloxifene is being further assessed in the STAR (Study of Tamoxifen and Raloxifene) trial, while anastrozole is being evaluated in the second IBIS-II (International Breast Intervention Study II). CONCLUSIONS: AIs, in particular anastrozole, are set to change the way that early breast cancer is treated. Effective and better-tolerated endocrine alternatives for breast cancer prevention may become available in the future.

Aged↗
PubMed2005

[Hormone therapy in breast cancer: the end of tamoxifen?].

The rise of aromatase inhibitors changes our habits in hormonal treatment in breast cancer. In premenopausal women tamoxifen with ovarian suppression remains reference treatment although the succession of the two treatments has not been explored as far as treatment duration is concerned. In post menopausal women the use of AI in the first line treatment gives a greater chance of response and a longer response duration than tamoxifen with a good tolerance profile. When both treatments are used, total duration of endocrine therapy (time to chemotherapy) is significantly longer for patients who receive AI in first line than for patients who receive tamoxifen first. In adjuvant treatment, tamoxifen and ovarian suppression remain references in premenopausal patients; therefore trials using aromatase inhibitors with LH-RH agonists are running. In post menopausal women aromatase inhibitors are challenging tamoxifen. Three large trials proved their superiority over tamoxifen. In the adjuvant setting AI may represent a beneficial approach, they can be used up front or in sequence with tamoxifen. The ideal combination or sequence of therapies requires investigations. At last duration of hormonal treatment remains an open deal.

Antineoplastic Agents, Hormonal↗
PubMed1995

Shear/peel bond strength of repositioned ceramic brackets.

Improper orthodontic bracket position may necessitate bracket removal and rebonding to establish correct bracket position. This procedure is necessary to use efficient orthodontic mechanics. The purpose of the study was to investigate (1) the amount of bonding resin remaining on single crystal bracket bases following electrothermal debonding, and (2) the bond strength of rebonded single crystal ceramic brackets under different treatment conditions. The bases of debonded, single crystal ceramic brackets (n = 100) were inspected for resin, classified with an adaptation of the adhesive remnant index (ARI), and evenly assigned to four experimental groups (n = 25). Groups were (1) silane coupling agent, (2) heat plus silane coupling agent, (3) hydrofluoric acid plus silane coupling agent, and (4) heat plus hydrofluoric acid plus silane coupling agent. An additional group of brackets not previously bonded was used as the control (n = 25). The brackets were bonded to 125 fresh bovine teeth. A force was applied 1 mm from the bracket-resin interface by a testing machine. The force measured in this experiment was shear/peel and the ratio of shear to peel was 0.53. The AI index showed 79% of the brackets had no resin on their bases. The shear/peel bond strnegth was significantly greater for the control group than all other groups (P < 0.01). Treatment of electrothermally debonded ceramic brackets with silane or heat plus silane resulted in bond strength greater than 9 MPa. The use of hydrofluoric acid significantly reduced the bond strength below 2 MPa.

Adhesives↗
PubMedDate not supplied

The effect of acipimox in patients with type 2 diabetes and persistent hyperlipidaemia.

A placebo-controlled, double-blind study was performed to assess the effect of 12 weeks treatment with acipimox (250 mg three times per day) on lipoproteins and glycaemic control in patients with Type 2 diabetes. All patients studied had persistent hyperlipidaemia despite acceptable glycaemic control on treatment with diet alone or diet and oral hypoglycaemic agents, achieving glycosylated haemoglobin (HbA1) of less than 10.5% but with fasting total triglycerides greater than 2.5 mmol l-1 or total cholesterol greater than 6.5 mmol l-1. Forty-eight patients were randomized to treatment, 21 to acipimox and 27 to placebo; 43 completed the trial. All patients had been diabetic for at least 1 year. Total cholesterol fell by 6% and total triglycerides by 19% following 12 weeks of acipimox, compared to rises in the placebo group of 1% and 16%, respectively (p less than 0.05). There were no significant differences between acipimox and placebo in the change in low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, apolipoproteins AI, AII, or B, or in glycaemic control during the treatment period. Acipimox is effective in reducing fasting total cholesterol and total triglycerides in patients with Type 2 diabetes with acceptable blood glucose control but persistent hyperlipidaemia. Acipimox does not adversely affect glucose tolerance.

Apolipoproteins↗
PubMed2006

Adjuvant endocrine therapy for early breast cancer.

Breast cancer is the most common cancer among women and about 80% of breast cancers express hormone receptors. Tamoxifen has been the most important form of adjuvant endocrine therapy over the last 25 years. The third generation aromatase inhibitors (AIs) are a new class of drugs challenging the central role of tamoxifen as adjuvant endocrine treatment in postmenopausal women with hormone receptor-positive breast cancer. Their effectiveness has been demonstrated in first line therapy as well in neoadjuvant setting with a statistically significant superiority over tamoxifen. Here we considered the role of adjuvant AIs in early stage breast cancer with an analysis reviewing the main adjuvant trials. We considered efficacy, side effects, optimal timing, duration of the therapy and whether specific subgroups may achieve particular benefit. In conclusion the upfront use of adjuvant anastrozole or letrozole is superior to tamoxifen with a good relative toxicity profile. Tamoxifen will continue to have a role where recurrence risk is low or if AI is poorly tolerated. Issues including the timing of administration (up-front or sequential), the duration of the therapy and the role of biomarkers such as PgR and HER2 in optimal selection remain unresolved.

Antineoplastic Agents, Hormonal↗