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At least 883 records · Page 49Linked to original sources
PubMed2006

Estrogen receptors evolution in neoadjuvant aromatase inhibitor (AI) therapy for breast cancer in elderly women: stability of hormonal receptor expression during treatment.

UNLABELLED: In France, 20% of breast cancers occur in women over the age of 70 and 10% in women over the age of 80. As these women are not included in screening programs, breast cancer is often diagnosed later, at the stage of a large tumor. PURPOSE: To analyze clinical response, possibilities of conservative treatment and course of hormonal receptors in patients receiving neoadjuvant aromatase inhibitor (AI) therapy for at least 6 months. PATIENTS AND METHODS: There were 75 patients, with a mean age of 75 +/- 8 years (range, 58-91 years) received AI for 6 months after the diagnosis of invasive breast cancer with positive hormonal receptors. Clinical and radiologic tumor reduction, the number of conservative treatments and the course of estrogens receptor-labeled cells were determined for each patient. RESULTS: All but 1 of these patients obtained clinical reduction of their tumor. Of these, 86% patients received conservative treatment. In the majority of patients, estrogen receptor (ER) level did not vary between the initial assay and analysis of the operative specimen. DISCUSSION AND CONCLUSION: Aromatase inhibitors are effective as neoadjuvant therapy in ER positive elderly patients with large tumors, as is tamoxifen. Changes in hormone receptor expression during treatment do not predict clinical response. In our experience, neoadjuvant AI therapy should be administered for at least 6 months to optimize clinical response before deciding upon surgery. Discrepancy observed in the literature could be explained by the duration of the treatment.

Aged↗
PubMed1994

Inverse association of anti-inflammatory treatments and Alzheimer's disease: initial results of a co-twin control study.

We conducted a co-twin control study among 50 elderly twin pairs with onsets of Alzheimer's disease (AD) separated by 3 or more years. Twenty-three male pairs (46%) were screened from the (U.S.) National Academy of Sciences-National Research Council Registry (NAS-NRC Registry) of World War II veteran twins; others (mostly women) had responded to advertisements or were referred from AD clinics. Twenty-six pairs (52%) were monozygous. The onset of AD was inversely associated with prior use of corticosteroids or ACTH (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.06 to 0.95; p = 0.04). Similar but weaker trends were present among pairs discordant for history of arthritis or for prior daily use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin. The association was strongest when we combined use of steroids/ACTH or NSAIDs post hoc into a single variable of anti-inflammatory drugs (AIs) (OR, 0.24; CI, 0.07 to 0.74; p = 0.01). The inverse relation was strong in female (volunteer) twin pairs but was not present in the younger men from the NAS-NRC Registry. AIs had typically been taken for arthritis or related conditions, but a similar result was apparent after controlling statistically for the arthritis variable (OR, 0.08; CI, 0.01 to 0.69; p = 0.02). AIs have been proposed as a means of retarding the progression of AD symptoms, and these data suggest that AIs may also prevent or delay the initial onset of AD symptoms. Because of limitations in the case-control method, our results require corroboration with hypothesis-driven research designed to control bias and confounding.

Age Factors↗
PubMed2005

Neuropathology in Alzheimer's disease: target of pharmacotherapy.

The pathogenesis of AD is complex and not yet fully understood. A number of factors, including amyloid plaques, NFTs, and inflammatory processes, are likely to contribute to development of the disease. Acetylcholine and glutamate are intimately involved in learning and memory. Hypotheses implicating defects within both neurotransmitter systems in AI) are recognized. This knowledge coupled with ongoing discoveries about the multiple pathophysiologic pathways involved in development and progression of AD has given rise to several plausible therapeutic targets. Therapies addressing some of these targets (ie, acetylcholine, glutamate) have already shown clinical efficacy in treating AD while other targets continue to be investigated.

Acetylcholine↗
PubMed2006

Neoadjuvant endocrine therapy in breast cancer.

The use of endocrine therapy is well established as a primary treatment for locally advanced breast cancer. However, despite the current popularity of neoadjuvant chemotherapy for operable tumours, there is relatively little published evidence for pre-operative endocrine therapy in operable disease, particularly outside of the elderly population. The wider use of aromatase inhibitors (AIs) has encouraged studies that compare the efficacy of AIs with tamoxifen in the neoadjuvant setting, but there remains a lack of comparison of neoadjuvant with adjuvant endocrine therapies. This review discusses the current evidence regarding primary endocrine therapy, along with the factors involved in choosing appropriate patients for neoadjuvant therapy and the current opinions on length of treatment time and measurement of response prior to surgery.

Antineoplastic Agents, Hormonal↗
PubMed2006

Immunization with specific polysaccharide antigen reduces alterations in corneal proteoglycans during experimental slime-producing Staphylococcus epidermidis keratitis.

PURPOSE: Staphylococcus epidermidis is a leading cause of bacterial keratitis associated with corneal damage. Corneal integrity is closely associated with matrix macromolecules, such as proteoglycans (PGs) and collagen. The aim of this study was to examine whether active immunization (AI) using a major immunogenic polysaccharide determinant of slime (20-kDa PS) as antigen, and passive immunization (PI) after administration of specific antibodies toward 20-kDa PS affect the distribution of PGs as well as corneal lesions in an experimental model of slime-producing S. epidermidis keratitis. METHODS: For AI, seven rabbits were immunized with 20-kDa PS, whereas for PI, seven rabbits received specific antibodies against 20-kDa PS. Lesions were graded clinically for a 21-day period. Levels of 20-kDa PS antibodies in serum and aqueous humor in both immunization groups were determined by ELISA. The distribution of certain extracellular matrix PGs during corneal healing was analyzed immunohistochemically. RESULTS: Levels of specific anti-20-kDa PS antibodies in serum and aqueous humor obtained after either AI or PI were significantly higher as compared with those in the respective nonimmunized control groups (p<0.001). Clinical grading showed that both AI and PI rabbits had a significantly less corneal damage as compared with infected nontreated rabbits. Immunohistochemical analyses for PGs exhibited significant differences to the wounded regions as compared with noninfected corneal tissue. Accumulation of keratan sulfate PGs and decorin was observed in the corneal stroma of infected rabbits and of heparan sulfate PGs around the new-formed vessels. This phenomenon was significantly reduced in immunized animals in accordance with macroscopically decreased corneal damage observed in these animals. CONCLUSIONS: Results of this study suggest a key role of 20-kDa PS and its antibodies as prophylactic and therapeutic agents in keratitis caused by slime-producing S. epidermidis.

Animals↗
PubMed2006

Interferon-alpha genes from Bos and Bubalus bubalus.

Interferon-a genes were cloned from six breeds of three species of two genera (three Chinese native cattle breeds of yellow cattle, wild yak and HuanHu domestic yak, one European breed of Holstein cow, and two water buffalo breeds of FuAn water buffalo and FuZhong water buffalo) by direct PCR. The PCR products were directly inserted into the expression vector to be sequenced and expressed. Sequence analysis showed that IFN-a genes of six clones were composed of 498 nucleotides, encoding a mature polypeptide with 166 amino acids. Compared with the published BoIFN-a subtypes, the IFN-a gene of Holstein cow had only one point mutation with the BoIFN-aA subtype. The IFN-a gene of yellow cattle was similar to the BoIFN-aD subtype with amino acid identity of 97.0% and may be considered as a new subtype, namely, BoIFN-aD1. The other four IFN-a genes, cloned from wild yak and HuanHu domestic yak, FuAn water buffalo, and FuZhong water buffalo, represented four new subtypes, namely, BoIFN-aI, BoIFN-aJ, BuIFN-a1, and BuIFN-a2, respectively. Each of the six clones was expressed in E. coli with molecular weight of approximately 20 kDa by SDS-PAGE and Western blot analyses. Antiviral activity assays showed that the six recombinant IFN-a (rIFN-a) all exhibited 1,000 times higher antiviral activity in the MDBK/VSV cell line than in the CEF/VSV one. Moreover, the rIFN-as could inhibit infectious bovine rhinotracheitis virus replication in the MDBK cell line using CPE inhibition method. The results suggested that rIFN-as a potential agent for clinical application against virus diseases in cattle industry.

Amino Acid Sequence↗
PubMed1995

Signal transduction by cholera toxin: processing in vesicular compartments does not require acidification.

In the polarized human intestinal epithelial cell line T84, signal transduction by cholera toxin (CT) follows a complex series of events in which CT enters the apical endosome and moves through multiple vesicular compartments before it activates adenylate cyclase. As with processing of many other surface ligands, it has been suggested that CT must enter acidic vesicles to exert its downstream effects. To determine if intravesicular pH may regulate signal transduction by CT, we examined the cAMP-dependent Cl- secretory response [short-circuit current (Isc)] to CT in T84 cell monolayers treated with chloroquine (500 microM), methylamine (50 mM), NH4Cl (10 mM), nigericin (4 microM), or bafilomycin A1 (1 microM). Each of these reagents collapsed intravesicular pH gradients as confirmed by accumulation of acridine orange within subcellular compartments of living T84 cells imaged by confocal epifluorescence microscopy. Both acidotropic amines and nigericin inhibited the cAMP-dependent Cl secretory response in T84 cells. However, none of these reagents specifically affected adenylate cyclase itself or coupling of adenylate cyclase with the heterotrimeric guanosinetriphosphatase Gs as judged by the secretory response to the adenosine 3',5'-cyclic monophosphate (cAMP) agonists vasoactive intestinal peptide (VIP), forskolin, or 8-bromo-cAMP. In vitro enzyme-linked immunosorbent assay showed that CT binding to ganglioside GM1 was not dependent on pH between 5.0 and 10. Maximal Isc elicited by apical CT relative to maximal Isc elicited by VIP was not affected by pretreatment with chloroquine, methylamine, NH4Cl, or bafilomycin AI. Nigericin was the only reagent to inhibit CT-induced Isc (5 +/- 2% maximal response to VIP). The data indicate that low intravesicular pH will have little or no effect on CT association with its membrane receptor GM1, or on subsequent processing/signal transduction events.

Acids↗
PubMed2005

Endocrine therapy trials of aromatase inhibitors for breast cancer in the adjuvant and prevention settings.

The recent past has witnessed the appearance of substantial data relating to endocrine therapy of breast cancer. In the adjuvant therapy setting in early breast cancer, several large, well-conducted, randomized, double-blind clinical trials have provided evidence for the value of the third-generation aromatase inhibitors (AI) anastrozole, exemestane, and letrozole. The three major studies to date [i.e., Arimidex, tamoxifen alone, or in combination (ATAC), International Exemestane Study (IES), and letrozole after 5 years of tamoxifen (MA.17)] evaluated three different populations of women from the standpoints of duration of prior tamoxifen and thus time since the treatment of the primary breast cancer. A consistent pattern of improvement in disease-free survival was seen whether the control arm was tamoxifen (ATAC and IES) or placebo following tamoxifen (MA.17). From a toxicity standpoint, the major findings with the AIs were a decreased incidence of thromboembolic events and endometrial cancers but an increase in musculoskeletal complaints and potential for decreasing bone density. The last issue should be clarified with ongoing studies addressing the impact of the three AIs on bone density and fractures. In summary, based on ATAC, IES, and MA.17, respectively, the following conclusions can be drawn relating to postmenopausal women with hormone receptor positive early breast cancer: anastrozole is a reasonable choice for initial endocrine adjuvant therapy, exemestane should be considered for women who have received 2 to 3 years of tamoxifen, and letrozole should be considered for those who have completed about 5 years of tamoxifen. In the prevention setting, tamoxifen has been evaluated in multiple trials involving >28,000 women and, despite clear evidence of benefit, the level of acceptance of this agent by women seems to be low. Two recently developed prevention trials, IBIS 2 and MAP.3, involve the study of aromatase inhibitors against a placebo control rather than tamoxifen. Whereas the recent adjuvant trials have established the value of the third-generation aromatase inhibitors in early-stage breast cancer, the marked reductions in contralateral breast cancers seen in these trials suggest they will be of value in the prevention setting in women at increased risk of developing the disease.

Antineoplastic Agents↗
PubMed2005

[Rosiglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice].

OBJECTIVE: To study the effect of rosiglitazone on atherosclerosis and potential mechanism in ApoE-knockout mice. METHODS: Thirty-two 6-week-old ApoE-knockout mice were used as atherosclerosis model in two groups: rosiglitazone group (n = 18) and control group (n = 14). Each group contained equal numbers of male and female mice. All mice were fed with normal chow diet. In addition to normal diet, rosiglitazone group received rosiglitazone 17 mg/kg of body weight/day. Venous bloods were collected for plasma glucose and lipid analysis, and aorta were prepared for morphologic and immunohistochemical analysis after 14 weeks. Aortic root (1 cm) was cut and prepared for paraffin slice. The histomorphometric analysis of atherosclerotic lesion was performed by means of HE; positive percentage of macrophage cell and tumor necrosis factor-alpha were measured by means of immunohistochemistry in cross section. The ratio of lesion/aortic wall surface in the rest aorta was measured by means of Sudan IV staining in longitudinal section. RESULTS: The amount of fatty streak in rosiglitazone group was significantly greater than that of control group; the gross number of lesions and the number of fibrous plaque and atheromatous plaque were similar in two groups. There were no differences in percentage of lesions in cross section in two groups. Rosiglitazone could significantly reduce the extend of atherosclerosis of longitudinal section, decrease the amount of macrophage cell and the level of tumor necrosis factor-alpha in lesions. The plasma glucose was normal and similar in two groups, and total cholesterol, LDL-cholesterol and triglyceride were significantly higher in rosiglitazone group. CONCLUSION: Rosiglitazone suppresses the expression of tumor necrosis factor-alpha, reduces the number of macrophage cell in lesion, and inhibits the development of atherosclerosis.

Animals↗
PubMed2000

Induction of apoptosis and growth inhibition of cultured human endometrial adenocarcinoma cells (Sawano) by an antitumor lipoprotein fraction of rice bran.

OBJECTIVE: A lipoprotein fraction extracted from rice bran (RBF) has been proved to be nontoxic to normal cells and to possess the ability to derange energy metabolism and induce apoptosis in Ehrlich ascites tumor cells. This study is designed to investigate the therapeutic effects of RBF as an antitumor substance on endometrial adenocarcinoma cells (Sawano). METHODS: Cultured human endometrial adenocarcinoma cells were treated with medium only (untreated), DMSO, or RBF at 100, 200, and 300 microg/ml. Mitotic indexes were counted by Giemsa stain and apoptotic index by fluorescent TUNEL stain for confocal laser scanning microscopy. DNA fragments were examined by agarose gel electrophoresis. RESULTS: Characteristic apoptotic morphology was observed in Giemsa-stained cells and further confirmed by confocal laser scanning microscopy in RBF-treated cells. Growth of Sawano cells was inhibited by RBF in a dose- and time-dependent manner. Apoptotic indexes (AI) showed an increasing tendency, and mitotic indexes (MI) showed a downward tendency. In 300 microg/ml RBF-treated Sawano cells, AI even reached 41.62 +/- 2. 23% and MI decreased to 0.79 +/- 0.08% at 96 h. Both showed significant differences from to controls and other RBF-treated groups. DNA agarose electrophoresis revealed DNA fragmentation in a ladder pattern. CONCLUSIONS: RBF can induce apoptosis of cultured human endometrial adenocarcinoma cells (Sawano) and inhibit its cell proliferation as an antitumor substance.

Adenocarcinoma↗
PubMed1978

A comparison of the anti-inflammatory effects of copper aspirinate and other copper salts in the rat and guinea pig.

A comparison of the anti-inflammatory (AI) activity of copper compounds in models of kaolin-induced paw oedema and u.v. erythema in the rat and guinea pig is described. The results demonstrated considerable species variation, the guinea pig being more sensitive to the AI and irritant effects of copper aspirinate and the other copper compounds. The route of administration of these compounds was also an important factor in interpreting AI activity obtained. Indeed, the counter-irritation effects of the copper compounds may be largely responsible for the AI activity obtained after subcutaneous administration. The comparison between copper aspirinate and aspirin, performed in order to determine whether a copper complex of an AI drug was more active than the parent AI compound, failed to produce a clear difference in activity although copper aspirinate was more effective than aspirin in certain cases. It is concluded that this study highlights the complexities of copper therapy against inflammatory processes and furthermore indicates the importance of species, the model of inflammation and route of drug administration in interpreting data obtained with copper containing compounds.

Animals↗
PubMed2005

Effect of hormone therapy on the elastic properties of the arteries in healthy postmenopausal women.

The aim of the study was to assess the effect of continuous hormone therapy (HT) for 1 yr on pulse wave analysis and central aortic pressure in healthy postmenopausal women. Sixty-five healthy postmenopausal women were randomly allocated to receive either conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 5 mg (CEE/MPA, Premelle 5, Wyeth-Ayerst Lab, Philadelphia, PA, no.=32) or no therapy (no.=33). Treatment was continuous, and the study period lasted 12 months. Central aortic pressure, augmentation and augmentation index (AI) were determined non-invasively using applanation tonometry. All measurements were performed at baseline and at the end of the study by the same person. Ns differences were found between baseline values and values at the end of the study in either the control or the CEE/MPA group in central systolic aortic pressure (107.0 +/- 13.1 vs 107.6 +/- 11.3 mmHg, p=0.80, and 110.8 +/- 10.8 vs 112.3 +/- 11.4 mmHg, p=0.23, respectively), augmentation (12.6 +/- 4.2 vs 11.9 +/- 4.8 mmHg, p=0.45 and 11.7 +/- 3.7 vs 12.6 +/- 4.2 mmHg, p=0.34, respectively), and percentage of AI (36.8 +/- 9.3 vs 36.3 +/- 10.3, p=0.81 and 34.1 +/- 8.9 vs 34.9 +/- 9.8, p=0.72, respectively). The results of this preliminary report suggest that HT for 1 yr does not have any significant effect on central aortic pressure and wave reflection in healthy postmenopausal women.

Aorta↗
PubMed2006

Oxidation of apolipoprotein B-containing lipoproteins and serum paraoxonase/arylesterase activities in major depressive disorder.

Major depressive disorder (MDD) is blaimed to play a role in the onset of coronary artery disease (CAD). The aim of the present study was to investigate serum paraoxonase/arylesterase activities and oxidation of apolipoprotein B-containing lipoproteins in patients with MDD. Oxidation of lipoproteins plays an important role in atherogenesis and the enzyme paraoxonase, has been shown to prevent lipoprotein oxidation. Furthermore, low paraoxonase activity was suggested to predict CAD. Eighty-six patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for MDD and 36 healthy control subjects were included in the study. Serum paraoxonase and arylesterase activities were determined spectrophotometrically. Malondialdehyde (MDA) levels of apolipoprotein B-containing lipoproteins were determined before (basal) and after incubation with copper-sulphate, that yielded basal- and Delta-MDA values, respectively. Serum paraoxonase/arylesterase activities were significantly reduced in the post-treatment group compared with the pre-treatment group. Basal-MDA (MDA) level was significantly higher in the MDD group compared with the control group. Delta-MDA level of the severe MDD group was significantly higher than that of the control group. There was a positive correlation between the oxidizability of apolipoprotein B-containing lipoproteins and the severity of the disease. Total cholesterol, HDL-cholesterol, LDL-cholesterol, apolipoprotein B levels were significantly higher and apolipoprotein AI levels were significantly lower in the MDD group compared with those of the control group. The findings of the present study suggest that: 1) antidepressant treatment might reduce serum paraoxonase activity/mass; 2) oxidation and oxidizability of apolipoprotein B-containing lipoproteins seem to be increased in MDD.

Adult↗
PubMed2005

Manipulation and control of the estrous cycle in pasture-based dairy cows.

Treatments designed to synchronize luteolysis, preovulatory follicular development, and ovulation, and resynchronize estrus after a first AI have improved responses to synchronization treatments. Protocols based only on the use of PGF result in variable onset of estrus. Concentrations of progesterone prior to administering PGF have affected submission rates and fertility while administration of estradiol benzoate (EB) after inducing luteolysis has improved the synchrony of estrus and ovulation in some studies. In pasture-based dairy cows, GnRH-based protocols have generally resulted in one-third of both anestrous and cycling cows conceiving following synchronization of ovulation and timed AI. Protocols which use intravaginal progesterone releasing inserts (IVP4) are effective in inducing estrus in over 90% of treated dairy cows. Resynchronization of estrus after reinsertion of an IVP4 also improves the synchrony of returns to estrus, but pregnancy rates to the first AI have been reduced in some studies, and submission rates at a resynchronized estrus are less than at the first synchronized estrus. Administration of EB can be used to synchronize follicle wave emergence in resynchronized cows with intervals to new wave emergence comparable to that in cows synchronized for a first AI, but plasma concentrations of progesterone following treatment may be reduced. Synchronization of estrus and ovulation can be enhanced by administration of EB or GnRH during proestrus, but dose, timing and stage of follicular development at the time of treatment can affect outcomes.

Administration, Intravaginal↗
PubMed1998

Effect of probucol on serum lipoprotein and apoprotein profiles in renal transplant patients.

The therapeutic effect of probucol on hypercholesterolemia in cyclosporine A (CyA)-treated renal transplant patients was prospectively studied. Twelve posttransplantation patients aged 34.2+/-2.5 years with serum total cholesterol (t-CHL) of 250 mg/dL or greater, whose serum creatinine was 2.9 mg/dL or less, and who had no diabetes mellitus or hypoproteinemia, were treated with probucol, 250 mg twice daily for 3 months. Seventeen age-matched (36.8+/-1.6 years) normal volunteers served as control. Blood was drawn after at least a 12-hour fast to measure lipids in serum and lipoprotein fractions, apoproteins (apo), lipoprotein fractions, lethicin cholesterol acyl transferase (LCAT), free fatty acids (FFA), and CHL-ester. Serum t-CHL, triglycerides (TG), and phospholipids (PL) in posttransplantation patients before treatment were significantly higher compared with normal control subjects. Very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) fractions in these patients were significantly expanded. The pretreatment levels of serum apo AII, B, CII, and CIII were significantly increased compared with those of normal controls. After treatment with probucol, serum t-CHL, LDL-CHL, high-density lipoprotein (HDL)-CHL, PL, LDL-PL, and apo AI were significantly decreased, and CHL-ester significantly increased compared with the pretreatment levels. These data suggest that although probucol causes a decrease in HDL-CHL, it may act anti-atherogenically by modulating HDL metabolism and stimulating reverse transfer of CHL from peripheral tissue.

Adult↗
PubMedDate not supplied

Effect of L-carnitine on plasma lipoprotein fatty acids pattern in patients with primary hyperlipoproteinemia.

PURPOSE: To investigate the effect of L-carnitine (L-C) administration on plasma lipoprotein fatty acids pattern in patients with primary hyperlipoprotinemia. PATIENTS AND METHODS: The effect of L-C on plasma lipoprotein fatty acids pattern was investigated in 24 male and female hyperlipoproteinemic patients, aged 51.3 +/- 7.8 years (lipoprotein phenotypes: IIb and IV, WHO, 1970). After hypolipidemic diet (P, 22%; C, 48%; L, 30%; S, 10%; M, 10%; PV, 10%, cholesterol < 300 mg/d) lasting 30 days, L-C was given at a daily dosage of 1 g t.i.d. for 90 days. RESULTS: Plasma total polyunsaturated to saturated fatty acids ratio (8/5) showed a statistically significant increase after L-C (baseline: 0.74 +/- 0.2, vs 120 days: 0.84 +/- 0.2; p < or = 0.03). A statistically significant decrease of HDLs 16:0 (baseline: 28.1 +/- 4.2 vs 120 days: 26.4 +/- 3.7; p < or = 0.002), HDL3s 16:0 (baseline: 28.6 +/- 4.5 vs 120 days: 26.9 +/- 3.6; p < or = 0.001) and VLDLs 14:0 (baseline: 2.0 +/- 0.8 vs 120 days: 1.6 +/- 0.6; p < or = 0.02), specular to a statistically significant increase of VLDL's 18:2 (baseline: 21.9 +/- 5.1 vs 120 days: 24.3 +/- 4.9; p < or = 0.01), was also observed. Plasma levels of total cholesterol and LDL-cholesterol were reduced after one month. Plasma apolipoprotein AI and B levels were significantly increased after 30 and 60 days of treatment with L-C. CONCLUSIONS: A less atherogenic plasma lipoprotein fatty acids profile was observed after 120 days of combined treatment with diet and L-C.

Carnitine↗
PubMed2003

Niacin, lipids, and heart disease.

Niacin is the most effective medication in current clinical use for increasing high-density lipoprotein (HDL) cholesterol. It has the broadest effect on the lipid profile, reducing all atherogenic apolipoprotein (apo) B and increasing all antiatherogenic apo AI-containing lipoproteins, resulting in significant reduction in atherosclerotic complications and total mortality in trials. Recent research indicates novel major target sites of action in the liver to 1) directly inhibit diacylglycerol acyltransferase 2 (DGAT2), explaining its effect on triglycerides and apo B lipoproteins, and 2) inhibit the HDL apo AI catabolism pathway, resulting in higher HDL levels. Such information may lead to new drug discovery and supply the rationale for combination with other lipid regulators that are known to have different mechanisms of action. Trial evidence shows that niacin is not only safe to use in persons with diabetes, but that its combination with 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) is also safe and effective. Recently, a new formulation of niacin has made it easier to tolerate and administer. Clinical trials are needed to determine whether niacin in combination with other lipid-modulating agents decreases the risk of cardiovascular events beyond the approximately 30% that has been noted with monotherapy.

Drug Therapy, Combination↗
PubMed1997

Vaginal delivery of new formulations of nonoxynol-9 coprecipitated with polyvinylpyrrolidone in rabbits. Comparisons between two formulation delivery systems.

The objective of this study was to assess the efficacy of two formulation delivery systems (FDS) in preventing the onset of pregnancy in rabbits. Nonoxynol-9 (N-9) was coprecipitated with polyvinylpyrrolidone (PVP), which yields PVP/ N-9, and prepared as capsules or tablets. Semen specimens were collected (from eight male rabbits), pooled, and used for in vitro spermicidal assessment or artificial insemination (AI). In vitro spermicidal assessment was performed by introducing and mixing the FDS containing PVP or PVP/N-9 with 1.0 mL of semen, followed by incubation at 37 degrees C for 6 h. Semen samples were taken at various time intervals to determine killing of spermatozoa and dissolution of the FDS. The efficacy of the FDS in preventing the onset of pregnancy was assessed by inserting the FDS vaginally. The does were artificially inseminated at 0, 0.5, and 6 h after insertion of the FDS vaginally. The number of pregnant does and newborn rabbits was recorded. In the in vitro spermicidal trial, semen specimens exposed to both FDS containing PVP/N-9 were killed within 10 to 15 min of incubation. Tablets containing PVP only or PVP/N-9 dissolved completely after 3 h of incubation. However, capsules did not dissolve completely by 6 h of incubation. The results obtained in the in vivo trial showed that both FDS exhibited some variations in preventing the onset of pregnancy over the various time intervals following the insertion of tablets or capsules and AI. The tablet seemed to be a more efficient delivery system than the capsule, yielding significantly lower pregnancy rates at all three time intervals assessed. The tablet FDS, as applied in this study, was found to be the most efficient mode of delivery of the tested spermicidal formulations.

Administration, Intravaginal↗