Dillapiol: a pyrethrum synergist for control of the Colorado potato beetle.

Dillapiol, the main constituent in dill Anethum sowa Roxb. ex Fleming (Apiaceae) oil and wild pepper, Piper aduncum L. (Piperaceae), is an effective cytochrome P450 inhibitor similar to piperonylbutoxide (PBO). Laboratory and field trials with pyrethrum Chrysanthemum cinerariifolium (Trevir.) vis. extracts combined with dillapiol (1:5 and 1:16 ratio) were effective against both insecticide-susceptible and -resistant Colorado potato beetle Leptinotarsa decemlineata (Say). In the laboratory, pyrethrum efficacy was increased 2.2-fold with the SS strain and 9.1-fold with the RS strains by using pyrethrum + dillapiol. Two field trials with the pyrethrum + dillapiol formulation demonstrated efficacy > or = 10 times than that of pyrethrum alone. The residual activity (half-life) of the combination exposed to direct sunlight was 3 h but it increased to 10.7 h by adding 2% of the sunscreen octylmethoxycinnamate.

Effects of short-day treatment on long-term growth performance and maturation of farmed Arctic charr Salvelinus alpinus reared in brackish water.

The effects of a 6 week short-day photoperiod followed by continuous light, applied during the juvenile phase of Arctic charr Salvelinus alpinus in fresh water on smoltification and on the long-term growth and maturity following transfer to brackish water (BW) (constant salinity of either 17 and 27 or increasing salinity in steps from 17 to 27) were investigated. Prior to salinity transfer, the juveniles were either reared at continuous light (C group) or reared for 6 weeks on a short day (8L:16D, S group) followed by continuous light (24L:0D). Increased salinity had negative effect on growth, with female fish reared at 17 salinity weighing 19 and 27% more than the salinity-step group (17-27) and the 27 salinity group, respectively. The stepwise acclimation to salinity had limited advantage in terms of growth rate. Short photoperiod for 6 weeks (November to January) followed by continuous light improved growth, but not seawater (SW) tolerance. Gill Na(+) , K(+) -ATPase activity and plasma Na(+) levels changed with time, indicating some variation in osmoregulatory capacity during the experimental period. Overall, there appear to be interactive effects on maturation from applying short-day photoperiod followed by rearing at higher salinities. Plasma leptin varied with time and may be linked to stress caused by the observed variations in osmoregulatory ability. It is concluded that changes in growth rates observed in this study are mainly related to rearing salinity with higher growth rates at lower salinities. Short-day photoperiod has some growth-inducing effects but did not improve SW tolerance. Farmers of S. alpinus using BW for land-based rearing should keep salinity at moderate and stable levels according to these results to obtain best growth.

Expression of polyhydroxybutyric acid as a model for metabolic engineering of soybean seed coats.

The feasibility of genetically engineering soybean seed coats to divert metabolism towards the production of novel biochemicals was tested. The genes phbA, phbB, phbC from Ralstonia eutropha each under the control of the seed coat peroxidase promoter were introduced into soybean and the production of polyhydroxybutyrate (PHB) was assayed. The analysis of seed coats arising from 4 independent transformation events demonstrated that PHB was produced at a mean of 0.12% seed coat dried weight with individual values up to 0.36%. These values demonstrate that it is possible to metabolically engineer soybean seed coats.

Ramon and maya ruins: an ecological, not an economic, relation.

Economically important trees such as ramón have been shown to have a high density in the civic-ceremonial core zone of ancient Maya ruins. The distribution of such trees is probably the result of their requirements for growth and reproduction, which are optimal on the ruins, and not because they are the descendants of trees planted by the Maya aristocracy.

Traditional medicines used by Q'eqchi' Maya to treat diabetic symptoms and their antiglycation potential.

ETHNOPHARMACOLOGICAL RELEVANCE: Because of the recent increase in type 2 diabetes and the need for complementary treatments in remote communities in many parts of the world, we undertook a study of treatments for diabetic symptoms used by traditional Q'eqchi' Maya healers of Belize. We used quantitative ethnobotany to rank culturally important taxa and subsequent pharmacological and phytochemical studies to assess bioactivity. MATERIALS AND METHODS: Antidiabetic plants identified in field interviews with traditional healers were ranked by syndromic importance value (SIV) based on 15 symptoms of diabetes. Species ranked with high SIV were tested in an assay relevant to many diabetes complications, the advanced glycation endproduct (AGE) inhibition assay. Active principles were identified by phytochemical analysis and bioassay. RESULTS: We collected over 70 plant species having a promising SIV score. The plants represented a broad range of neotropical taxa. Selected Q'eqchi' antidiabetic plants with high SIV were collected in bulk and tested in the advanced glycation endproduct (AGE) inhibition assay. All plant extracts showed AGE inhibition and the half maximal inhibitory concentration (IC50) ranged from 40.8 to 733 µg/mL, while the most active species was Tynanthus guatemalensis Donn (Bignoniaceae). A linear regression showed a significant relationship between 1/ IC50 and SIV. Phytochemical analysis revealed the presence of verbascoside, as a major component and active principle of the T guatemalensis which had an IC50 = 5.1 µg/mL, comparable to the positive control quercetin. CONCLUSION: The results reveal a rich botanical tradition of antidiabetic symptom treatments among the Q'eqchi'. Study of highly ranked plants revealed their activity in AGE inhibition correlated with SIV. T. guatemalensis was identified as a promising species for further evaluation and local use.

Investigation of the antioxidant activity of African potato (Hypoxis hemerocallidea).

African potato (AP) is widely used as an immune booster for the treatment of various ailments. The norlignan glycoside hypoxoside, a major phytoconstituent of AP, its aglycon rooperol, and an aqueous preparation of lyophilized AP corms were screened for in vitro antioxidant activity using the DPPH (1,1-diphenyl-2-picryl hydrazine) and FRAP (ferric reducing ability of plasma) tests. Inhibition of quinolinic acid (QA) induced lipid peroxidation in rat liver tissue was studied in vitro using the thiobarbituric assay (TBA). Superoxide free radical scavenging activity was determined by the nitroblue tetrazolium assay. An isocratic HPLC method was developed to quantitatively determine both hypoxoside and rooperol concurrently. While rooperol and AP extracts reduced QA-induced lipid peroxidation in rat liver homogenates and significantly scavenged the superoxide anion at pharmacological doses, in comparison, hypoxoside was virtually devoid of activity. Since hypoxoside is converted to rooperol in vivo following administration of AP, the results indicate that the hypoxoside component in AP could have value as an antioxidant prodrug.

MUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs.

The PD-L1/PD-1 pathway is a critical component of the immunosuppressive tumor microenvironment in acute myeloid leukemia (AML), but little is known about its regulation. We investigated the role of the MUC1 oncoprotein in modulating PD-L1 expression in AML. Silencing of MUC1 in AML cell lines suppressed PD-L1 expression without a decrease in PD-L1 mRNA levels, suggesting a post-transcriptional mechanism of regulation. We identified the microRNAs miR-200c and miR-34a as key regulators of PD-L1 expression in AML. Silencing of MUC1 in AML cells led to a marked increase in miR-200c and miR-34a levels, without changes in precursor microRNA, suggesting that MUC1 might regulate microRNA-processing. MUC1 signaling decreased the expression of the microRNA-processing protein DICER, via the suppression of c-Jun activity. NanoString (Seattle, WA, USA) array of MUC1-silenced AML cells demonstrated an increase in the majority of probed microRNAs. In an immunocompetent murine AML model, targeting of MUC1 led to a significant increase in leukemia-specific T cells. In concert, targeting MUC1 signaling in human AML cells resulted in enhanced sensitivity to T-cell-mediated lysis. These findings suggest MUC1 is a critical regulator of PD-L1 expression via its effects on microRNA levels and represents a potential therapeutic target to enhance anti-tumor immunity.

Location, identification, and size distribution of depleted uranium grains in reservoir sediments.

The location, nature, and size distribution of uranium-rich grains in sediment layers can be identified by sunbursts of etched particle tracks if each sample is pressed against a track detector, next irradiated with thermal neutrons, and the detectors then chemically etched to reveal fission tracks. The total track abundance from the sample is a measure of the 235U content; hence, if the bulk uranium (mostly 238U) has been measured, the two sets of results give the depletion or enrichment of the uranium. Sunbursts of tracks mark the locations of low-abundance, high-uranium grains allowing them to be singled out for further study.

Anxiolytic activity and active principles of Piper amalago (Piperaceae), a medicinal plant used by the Q'eqchi' Maya to treat susto, a culture-bound illness.

ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant, Piper amalago L. (Piperaceae), is used traditionally by Q'eqchi' Maya healers for the treatment of "susto" a culture-bound syndrome. Previous research suggests that susto symptoms may be a manifestation of anxiety. The objectives were to characterize the effect of ethanolic extract of P. amalago in behavioral assays of anxiety at doses representative of traditional use and to isolate active principles. MATERIALS AND METHODS: Rats treated orally with low dose ethanolic extracts of P. amalago leaves (8-75mg/kg) were tested in several behavioral paradigms including the elevated plus maze (EPM), social interaction (SI), and conditioned emotional response (CER) tests, and compared to diazepam, a positive control. The active anxiolytic principle was isolated by bioassay guided isolation using an in vitro GABAA competitive binding assay. RESULTS: Extracts had significant anxiolytic activity in all behavioral tests, with the strongest activity in the SI and the CER paradigms. In an in vitro GABAA competitive binding assay, a 66.5µg/mL concentration of P. amalago ethanol extract displaced 50% of the GABAA-BZD receptor ligand [(3)H]-Flunitrazepam. Bioassay-guided fractionation identified a furofuran lignan, a molecule with structural similarity to yangambin, with high affinity for the GABAA-BZD receptor as the principle bioactive. CONCLUSION: The results suggest that the ethnobotanical use of this plant may have a pharmacological basis in its anxiolytic activity, as demonstrated in animal behaviour tests.

Ethnomedicinal uses of Momordicacharantia (Cucurbitaceae) in Togo and relation to its phytochemistry and biological activity.

Investigation of the traditional uses of Momordica charantia (Cucurbitaceae) in Togo (West Africa) showed that it is one of the most important local medicinal plants both for ritual and ethnomedical practices. There was a high degree of consensus (>50%) for use in the treatment of gastrointestinal and viral disease among 47 groups of village informants in the general population, while 19 traditional healers reported a larger and broader set of uses. The use by informants in Gaur and Kwa language groups was not significantly different. Lyophilized Momordica charantia extracts prepared from accessions collected in Togo showed high antiviral activity (<5 microg/ml) against Sindbis and Herpes simplex type 1 viruses and anthelmintic activity against Caenorhabditis elegans at 500 microg/ml. Presence in the leaves of the triterpene glycosides momordicins I and II follows biological activity of the plant extracts. However, momordicins were found to be anthelmintic but not antiviral. Traditional healers collected plants in dry areas where momordicin content is greater.

Efficacy of botanical insecticides from Piper species (Piperaceae) extracts for control of Ruropean chafer (Coleoptera: Scarabaeidae).

Biopesticides, including botanicals, can offer a safe and effective alternative to conventional insecticides for controlling major insect pests within an integrated pest management program. The current study highlights the practical application of a botanical insecticide for controlling a major insect pest of turfgrass: European chafer, Rhizotrogus majalis (Razoumowsky). Greenhouse and field trials were conducted to test the efficacy of a botanical formulation based on black pepper, Piper nigrum L. (Piperaceae), seed extracts to R. majalis larvae. The 7-d P. nigrum extract LC50 for R. majalis third instars was 2.5%. Successful treatment in the field was accomplished with the application of a 2% P. nigrum formulation to turfgrass infested with R. majalis second and third instars, whereas 4% extract was required in a second field trial with older third instars. The 2% pepper extract activity was comparable with the conventional insecticide diazinon in the first field trial. However, the 4% pepper extracts significantly affected the earthworm populations in treated plots compared with diazinon in the second field trail. The analysis of soil residues for piperamides in the P. nigrum extract determined a half-life of 1 - 2.6 d in the first and second field trials, respectively. This confirmed the expectation that under field conditions the residual activity would be less than conventional insecticides, thereby reducing the environmental risk associated with pesticide use. We recommend the pepper formulation for spot treatment applications when population densities reveal an epicenter of infestation rather than broadcasting over large areas, thus helping to minimize cost and negative affects on nontarget invertebrates.

American ginseng (Panax quinquefolius L.) attenuates postprandial glycemia in a time-dependent but not dose-dependent manner in healthy individuals.

BACKGROUND: We previously showed that 3 g American ginseng administered 40 min before an oral glucose challenge significantly reduces postprandial glycemia in subjects without diabetes. Whether this effect can be replicated with doses <3 g and administration times closer to the oral glucose challenge is unclear. OBJECTIVE: Our objective was to study the dosing and timing effects of American ginseng on postprandial glycemia. DESIGN: In a random crossover design, 12 healthy individuals [X +/- SEM age: 42 +/- 7 y; body mass index (BMI; in kg/m2): 24.1 +/- 1.1] received 16 treatments: 0 (placebo), 1, 2, or 3 g American ginseng at 40, 20, 10, or 0 min before a 25-g oral glucose challenge. Capillary blood was collected before administration and at 0, 15, 30, 45, 60, and 90 min after the start of the glucose challenge. RESULTS: Two-way analysis of variance showed that the main effects of treatment and administration time were significant (P < 0.05). Glycemia was lower over the last 45 min of the test after doses of 1, 2, or 3 g ginseng than after placebo (P < 0.05); there were no significant differences between doses. The reductions in the areas under the curve for these 3 doses were 14.4 +/- 6.5%, 10.6 +/- 4.0%, and 9.1 +/- 6%, respectively. Glycemia in the last hour of the test and area under the curve were significantly lower when ginseng was administered 40 min before the challenge than when it was administered 20, 10, or 0 min before the challenge (P < 0.05). CONCLUSIONS: American ginseng reduced postprandial glycemia in subjects without diabetes. These reductions were time dependent but not dose dependent: an effect was seen only when the ginseng was administered 40 min before the challenge. Doses within the range of 1-3 g were equally effective.

Traditionally-used antimalarials from the Meliaceae.

A quantitative ethnobotanical approach to antimalarial drug discovery led to the identification of Lansium domesticum Corr. Ser. (Meliaceae) as an important antimalarial used by Kenyah Dyak healers in Indonesian Borneo. Triterpenoid lansiolides with antimalarial activity were isolated from the bark and shown to have activity in both in vitro bioassays with Plasmodium falciparum, and in mice infected with P. berghei. A survey of African and tropical American Meliaceae led to further development of the limonoid gedunin from the traditionally used medicinal plants, tropical cedar, Cedrela odorata L., and neem, Azadirachta indica A. Juss. Gedunin has significant in vitro activity but initially showed poor in vivo activity. In vivo activity was improved by (1) incorporation into an easy to absorb suspension, (2) preparation of a more stable compound, 7-methoxygedunin; and (3) synergism with dillapiol, a cytochrome P450 3A4 inhibitor. The results show the potential for both antimalarial drug and phytomedicine development from traditionally used plants.

Adrenal insufficiency in the antiphospholipid antibody syndrome.

OBJECTIVE: Adrenal insufficiency (AI) is a rare complication of the antiphospholipid antibody syndrome (APS). The objective of this report is to describe a case and review the published literature to enhance recognition of this potentially fatal disorder by emphasizing its course, diagnosis, and cause. DATA SOURCES: A bibliographic database with the indexing terms adrenal insufficiency, adrenal hemorrhage, adrenal thrombosis, APS, systemic lupus erythematosus, with the constraints of human subjects only, was used. STUDY SELECTION: All 27 reports meeting the indexing terms were selected for review. DATA EXTRACTION: The specific criteria used for data extraction articles included course of the disease, causation, clinical and laboratory diagnostic criteria, and therapeutic intervention. DATA SYNTHESIS: Our patient is a previously health woman who developed a respiratory tract infection, followed by a prolonged illness with fever, hypotension, nausea, depression, and venous thromboses. She was found to have AI and APS that was alleviated with hydrocortisone and anticoagulation. Initially, her adrenal glands were normal on CT scan but subsequently became enlarged and later atrophic. Of the 27 previous case reports, a majority had thromboses and typical clinical and laboratory manifestations of AI. Hemorrhagic infarction of the adrenal gland appears to be the mechanism for AI in the APS. IgG and IgM anticardiolipin antibodies are most commonly reported in association with AI in APS. CONCLUSIONS: The hypercoagulable state in the APS may lead to adrenal vein thrombosis and subsequently to hemorrhagic necrosis of the adrenal gland. This complication of APS is important to recognize because it may be fatal if untreated.

Autoantibodies and common viral illnesses.

OBJECTIVES: To review the literature about common autoantibodies produced in association with viral infection. METHODS: Medline review of the medical literature published in English. RESULTS: Common viral infections are often associated with low-titer, polyspecific autoantibodies. However, high-titer antinuclear antibodies, double-stranded DNA antibodies, anticardiolipin antibodies, and other subtype antibodies may be found. Hepatitis C and B virus, human immunodeficiency virus, and parvovirus B19 appear to be associated with autoantibodies more commonly than other viruses. CONCLUSIONS: Transient autoantibodies resulting from viral infections are not uncommon. Clinical and laboratory follow-up over time will help distinguish between connective tissue disease and self-limited illness.

Methyl jasmonate increases reported alkamides and ketoalkene/ynes in Echinacea pallida (Asteraceae).

Methyl jasmonate (MJ), a naturally-occurring plant cellular signal molecule, was found to induce production of lipophilic secondary metabolites in Echinacea pallida seedlings. Seedling aerial parts were sprayed with 100 ppm MJ, and roots were harvested and extracted 24 h later. Lipophilic root extracts, separated by HPLC, revealed significant increases (P< 0.05) in six alkamides or related ketoalkene/ynes produced by 34 day-old plants and in seven compounds produced by 58 day-old plants.

Predicting quantitative phytochemical markers in single Echinacea plants or clones from their DNA fingerprints.

Amplified restricted fragment length polymorphism (AFLP) data analysis was found to be a statistically significant predictor of phytochemical markers in cultivated Echinacea purpurea germplasm and some related wild species. Over 50 accessions grown under greenhouse conditions were subjected to AFLP analysis and the same assessed for content of tetraene and cichoric acid by high pressure liquid chromatography. The first and second canonical correlation of DNA variables and the phytochemical variables were significant. Individual regressions of cichoric acid and dodeca-2E, 4E, 8Z, 10E/Z-tetraenoic acid isobutyl amide predicted by DNA polymorphism analysis against actual HPLC determined values were nearly linear. Mantel's test showed that there was a weak correlation but a strong association of values of the phytochemical variables and the DNA polymorphism data.

The anti-HIV activities of photoactive terthiophenes.

Various synthetic analogues of the naturally occurring terthiophene, alpha-terthienyl (alpha T), were evaluated for anti-human immunodeficiency virus (HIV) activity. The compounds were incubated individually with a known amount of the virus, with or without UVA radiation (long-wavelength ultraviolet) and residual virus was monitored for its ability to produce cytopathic effects in cell culture and the production of virus-specific protein (p24). The basic terthiophene structure was essential for good anti-HIV activity, although various side chains, such as alcohols, bromo, methyl, thiomethyl and trimethylsilyl groups, permitted retention of maximum activity. Under optimum conditions, as little as 12 ng/mL of these compounds (i.e. approximately 3 x 10(-8) M) could inactivate 10(3) infectious virions. None of the compounds however were more active than alpha T itself. In all cases, UVA radiation was essential. Several side chains decreased the antiviral efficacy, and some side chains abrogated the activity.

Efficiency of the photoprocesses leading to singlet oxygen (1 delta g) generation by alpha-terthienyl: optical absorption, optoacoustic calorimetry and infrared luminescence studies.

The triplet energy of alpha-terthienyl has been determined by heavy atom-induced optical absorption: the value of 39.7 +/- 1.5 kcal/mol is consistent with earlier energy transfer work. Combining this result with calorimetric data from optoacoustic calorimetry indicates that intersystem crossing occurs with at least 90% efficiency in polar and non-polar solvents. The quantum yields for singlet oxygen formation via energy transfer from triplet alpha-terthienyl have been obtained from time-resolved measurements of its IR phosphorescence: these yields are in the 0.6-0.8 range in non-polar and polar (hydroxylic and non-hydroxylic) solvents.