Patients' understanding of how genotype variation affects benefits of tamoxifen therapy for breast cancer.

BACKGROUND: CYP2D6 is a critical enzyme in the metabolism of tamoxifen and potentially a key determinant in breast cancer outcomes. Our study examined patients' beliefs about how the CYP2D6 genotype would affect their prognoses. METHODS: Women enrolled in a pharmacogenomic clinical trial and on tamoxifen for prevention or treatment of breast cancer underwent CYP2D6 genotyping (EM = extensive, IM = intermediate, PM = poor metabolizing alleles). The informed consent said that the purpose of the trial was to examine effects of dose adjustment based on genotype, but that clinical benefits were uncertain. Our embedded sub-study surveyed 320 patients prior to receiving their genotypes. We experimentally manipulated 6 vignettes to describe hypothetical tamoxifen treatment (no or yes) and hypothetical genotype (EM, IM or PM). For each vignette, women gave their perceived recurrence risk (RR; 0-100%). RESULTS: Women believed that genotype would not affect their RR if they did not take tamoxifen (p = 0.06). However, women believed that if prescribed tamoxifen, genotype would affect their RR (22% if EM, 30% if IM and 40% if PM, p < 0.001). CONCLUSION: Women believed that extensive tamoxifen metabolizers had better prognoses, despite study materials stating uncertainty about any benefit. The rapidly changing nature of genomic science calls for caution when communicating clinical utility.

Antinociceptive effect of Russelia equisetiformis leave extracts: identification of its active constituents.

This study examines the antinociceptive effect of the whole plant extracts of Russelia equisetiformis. The result shows the ethylacetate fraction to be the most active, while the dichloromethane fraction exhibited least activity. The major isolated compound from the ethylacetate showed a tremendous activity on acetic acid induced writhing with less activity on tail-flick response in mice. The structures of the two compounds were assigned on the basis of spectroscopic data. Occurrence of these compounds in Russelia is reported here for the first time, and the results confirm the traditional uses of R. equisetiformis in the treatment of inflammation and pain.

Central nervous system depressant activity of Russelia equisetiformis.

The central nervous system depressant activity of the crude methanol extract (REC) and fractions (RE1, RE2, and RE3) of Russelia equisetiformis were evaluated in mice using the following models: amphetamine-induced stereotypy, picrotoxin-induced convulsion and phenobarbitone sleeping time. At 200-400 mg/kg, REC significantly increased phenobarbitone-sleeping time [P < 0.05] in a dose- dependent manner and also reduced the sleep latency significantly [P < 0.05]. The fractions, at doses 1.5 mg/kg for RE1 and 20 mg/kg for RE2 and RE3 also significantly prolonged Phenobarbitone sleeping time and sleep latency [P < 0.05]. Picrotoxin-induced convulsion was not prevented by 100-400 mg/kg of REC but this dose range significantly prolonged seizure latency. A significant reduction [P < 0.05] in amphetamine-induced stereotype behavior was observed with 200 mg/kg REC, but there was no protection against amphetamine-induced mortality. The results of this study suggest that Russelia equisetiformis methanol extract possesses central nervous system depressant activities.

Evaluation of the anti-inflammatory and analgesic properties of the extract of Russelia equisetiformis (Schlecht & Cham) Scrophulariacae.

A methanolic extract of Russelia equisetiformis whole plant was studied for anti-inflammatory and analgesic activities in rats and mice using carrageenan-induced rat paw oedema, acetic-acid-induced writhing and tail-flick test. The extract, at 10, 20 and 40 mg/kg, significantly (P <0.05) inhibited carrageenan-induced oedema in rats. Abdominal constriction induced by acetic acid was also inhibited by the extract, within the same dose range. The extract at the same dose also prolonged the latency period in the tail-flick response test, which was reverted by naloxone. The results suggested that the extract possesses potential anti-inflammatory and analgesic properties.

Studies on the anti-inflammatory properties of Entada abyssinica.

The defatted methanolic extract of Entada abyssinica was evaluated for anti-inflammatory activity in acute and chronic models of inflammation. The extract (50--200 mg/kg, p.o.) exhibited dose-dependent and significant inhibition of both the carrageenan-induced rat paw oedema and granuloma tissue formation in rats. The extract (50--200 mg/kg, p.o.) was also found to inhibit the acetic acid-induced vascular permeability in a dose-dependent fashion in mice. This study demonstrated the anti-inflammatory activity of Entada abyssinica.

Evaluation of the anti-inflammatory and analgesic properties of Chasmanthera dependens leaf methanol extract.

A methanol extract of the dried leaves of Chasmanthera dependens was investigated for anti-inflammatory and analgesic activities. The extract (100--400 mg/kg, p.o.) produced dose-related inhibition of carrageenan-induced paw oedema and cotton pellet-induced granuloma in rats. Furthermore, an inhibition in the leakage of Evan's blue induced by acetic acid was observed in mice. At same doses, analgesic effect was also observed on writhing response induced by acetic acid as well as on the early and late phase of formalin-induced paw licking in mice.

Studies on the anti-inflammatory and related pharmacological properties of the aqueous extract of Bridelia ferruginea stem bark.

The anti-inflammatory profile of the aqueous extract of Bridelia ferruginea stem bark was investigated using both in vivo and in vitro models. The extract exhibited strong topical anti-inflammatory effect shown as inhibition of croton oil-induced ear oedema in mice, and reduced hind-paw swelling and growth retardation in the adjuvant-induced arthritis model in rats, following oral administration at 10, 20, 40 or 80 mg/kg. The extract (10-80 mg/kg, p.o.) caused an inhibition of increase in vascular permeability in both cyclophosphamide-induced haemorrhagic cystitis and acetic acid-induced vascular permeability in rats and mice, respectively. B. ferruginea produced stabilization of erythrocytes exposed to heat and stress-induced lysis. Antipyretic and analgesic properties of the extract were also observed.

Studies on the anti-inflammatory, antipyretic and analgesic properties of Alstonia boonei stem bark.

The methanol extract of the stem bark of Alstonia boonei was investigated for anti-inflammatory property. The analgesic and antipyretic properties of the extract was also evaluated. The extract caused a significant (P<0.05) inhibition of the carrageenan-induced paw oedema, cotton pellet granuloma, and exhibited an anti-arthritic activity in rats. Vascular permeability induced by acetic acid in the peritoneum of mice was also inhibited. The extract also produced marked analgesic activity by reduction of writhings induced by acetic acid, as well as the early and late phases of paw licking in mice. A significant (P<0.05) reduction in hyperpyrexia in mice was also produced by the extract. This study has established anti-inflammatory, analgesic and antipyretic activities of the stem bark of A. boonei.

Effects of the aqueous extract of Bridelia ferruginea stem bark on carrageenan-induced oedema and granuloma tissue formation in rats and mice.

The anti-inflammatory activity of the aqueous extract of the stem bark of Bridelia ferruginea was evaluated using carrageenan-induced paw oedema in rats and mice, and the cotton pellet granuloma method. The extract at doses ranging from 10 to 80 mg/kg p.o. significantly inhibited the carrageenan-induced rat paw oedema, with an ID50 value of 36 mg/kg. However, a low activity was produced in the mouse paw oedema. The extract also suppressed the granulomatous tissue formation of chronic inflammation. B. ferruginea therefore proved to be effective in both the acute and chronic phases of the inflammatory process.

Central nervous system depressant effect of Hoslundia opposita vahl.

The chloroform extract of the dried root of Hoslundia opposita has been evaluated for effects on the central nervous system (CNS). The extract significantly potentiated the phenobarbitone sleeping time in mice and produced a 60% protection against leptazol-induced convulsion. Neuropharmacological screening revealed CNS depression.

Biological effects of Myristica fragrans (nutmeg) extract.

The chloroform extract of nutmeg has been evaluated for antiinflammatory, analgesic and antithrombotic activities in rodents. The extract inhibited the carrageenan-induced rat paw oedema, produced a reduction in writhings induced by acetic acid in mice and offered protection against thrombosis induced by ADP/adrenaline mixture in mice.

Investigation of the effects of selected medicinal plants on experimental thrombosis.

Six medicinal plants indigenous to Africa were evaluated for their activity on experimental thrombosis in mice. Of the plants screened, the extract of Commiphora molmol exhibited the strongest antithrombotic activity, while the extract of Ageratum conyzoides showed no marked activity. This study established the antithrombotic effect of the extracts of Azadiractha indica, Bridelia ferruginea, Commiphora molmol, Garcinia kola and Curcuma longa.

Evaluation of the anti-diabetic property of Morinda lucida leaves in streptozotocin-diabetic rats.

The hypoglycaemic and anti-hyperglycaemic activities of a methanol extract of Morinda lucida Benth. (Rubiaceae) leaves were studied in normal and streptozotocin-diabetic rats. In normal rats, the extract demonstrated a significant (P < 0.05) and dose-dependent hypoglycaemic activity within 4 h after oral administration. The plasma glucose level of 400 mg kg(-1) of the extract at 4 h was 42.5 +/- 0.4 mg/100 mL (control 67.4 +/- 1.2 mg/100 mL). After 12 h, the plasma glucose level of rats administered 50, 100, 200 or 400 mg kg(-1) extract fell to 51.9 +/- 1.2, 47.3 +/- 0.8, 43.1 +/- 0.4 and 40.0 +/- 0.5 mg/100 mL, respectively. In hyperglycaemic rats, the extract produced a significant (P < 0.05) anti-diabetic effect from day 3 after oral administration, with 400 mg kg(-1) extract-treated animals having a plasma glucose level of 248.7 +/- 5.3 mg/100 mL compared with glibenclamide (10 mg kg(-1))-treated animals with a plasma glucose level of 251.5 +/- 5.8 mg/100 mL. These results suggest that the leaves of Morinda lucida have a strong glucose lowering property when administered to streptozotocin-treated rats.