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Molecular aspects of allergic contact dermatitis to plants. Recent progress in phytodermatochemistry.

A classification of plants based on the chemical structures of their skin sensitizers is presented. A whole range of chemical structures of contact sensitizers exists in plants containing sesquiterpene lactones (Compositae, Frullania, Lauraceae etc.), tulipalin (Tulipa, Alstroemeria etc.), quinones (Primula and tropical woods), long chain phenols (Anacardiaceae, Ginkgoaceae) and miscellaneous structures such as aldehydes, ketones, terpene hydrocarbons etc. Knowledge of allergens in various plants allows prediction of cross-reactivity.

Allergens↗

[Trichome].

A 4 year-old boy presented an acute pruriginous dermatitis of the hands, forearms and abdomen. A skin surface biopsy revealed numerous trichomes, small prickles present on plants. These trichomes were those of prickly pears and stuck deeply in the skin, inducing an inflammatory reaction known as Sabra dermatitis. A number of plant dermatitides are due to the presence of trichomes such as those due to linden, primula, wild rose or nettle.

Child, Preschool↗

6-Tridecylresorcylic acid, a novel ATPase inhibitor that blocks the contractile apparatus of skeletal muscle proteins.

6-Tridecylresorcylic acid (TRA) isolated from a primula Lysimachia japonica Thunb. inhibited contraction of myofibrils, superprecipitation of myosin B, and ATPase activities of myosin and actomyosin prepared from rabbit skeletal muscle in a dose-dependent manner. The IC50 values in molarity of TRA were as follows: myosin (K+,EDTA)-ATPase, 3.5 X 10(-6); myosin Ca2+-ATPase, 3.5 X 10(-5); and actomyosin Mg2+-ATPase, 1.6 X 10(-5). The inhibition of ATPase activity of myofibrils by TRA was virtually reversed by washing with the fresh saline solution. Kinetic analysis of inhibitory effects of TRA suggests that the inhibition of (K+,EDTA)-ATPase activity of myosin or subfragment-1 is parabolic noncompetitive. TRA had no effect on alkaline phosphatase and choline acetyltransferase activities. TRA may provide a useful chemical tool for the study of the molecular mechanisms of actin-myosin contractile systems.

Actomyosin↗

[Allergic contact dermatitis caused by plants].

The proliferation of house and garden plants, some of them highly sensitizing, produced by the general improvement of the standard of living, is causing an increase in the number of cases of contact dermatitis from plants with both irritative and allergic mechanisms. During the past 12 years, we have studied 43 cases of allergic eczema caused by plant contact as primary sensitization which supposes 2.4% of the patients with allergic contact dermatitis attended in our Services. The majority of patients were women (65%) as opposed to 35% men while the ages varied from 12 to 70 years with an average of 44.5. Below the age of 25 there were only 3 cases (6.9%) 12, 18 and 20 years respectively. In the clinical study, as well as the profession, secondary activities and hobbies were also evaluated. Through localization of lesions, an attempt was made to determine how the patient came in to contact with the different plants. The diagnosis was confirmed by the use of epicutaneous tests, as recommended by the ICDRG (3). Some plants in a natural state were used but etheral extracts were preferred. In cases of photo-dermatitis, photo-patch-tests were carried out using standard photo-sensitizers and suspected plants. The plants found to be responsible were: Allium (garlic) in 11 cases, Frullania in 8, Primula (primrose) in 8. Compositae (composites) in 6, Pinus (pine) in 3, Umbelliferae (umbellifers) in 3, Philodendron (philodendron) in 1, Pelagonium (pelargonium) in 1, Citrus (citrus) in 1 and Chlorophora (iroko) in 1. The frequency of reactions to garlic and primrose is particularly interesting and their characteristics will be the object of a later study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Microalgae-Mediated Synthesis of Gold Nanoparticles from Indonesian Chlorella vulgaris InaCC M205 with Potential Anticancer Properties for Biomedical Application.

Sustainable nanomaterial synthesis has emerged as a critical strategy to reduce the environmental burden associated with conventional chemical synthesis method. Microalgae-derived biomolecules offer a promising platform for the green production of metal nanoparticles due to their rich bioactive compounds capable of acting as natural reducing and stabilizing agents. Here, we report the eco-friendly synthesis of gold nanoparticles (AuNPs) using extract of Indonesian microalga Chlorella vulgaris extract. To optimize the synthesis process, the effects of precursor-to-extract ratio, temperature, and incubation time were evaluated. Optimal synthesis of C5-AuNPs was obtained at 37 °C for 20 h with precursor to extract ratio of 6:4, resulting in moderately stable C5-AuNPs characterized by a surface plasmon resonance (SPR) peak at 541 nm. Furthermore, Fourier-transmission infra-red (FT-IR) analysis revealed the involvement of functional groups of C. vulgaris extract in the interaction with Au+ during the production of C5-AuNPs. Transmission electron microscopy (TEM) demonstrated the formation of uniformly spherical nanoparticles with an average diameter of approximately 8.8 nm. Biological evaluation showed that the synthesized C5-AuNPs exerted pronounced dose-dependent cytotoxicity against MCF-7 breast cancer cells with an IC50 threshold of 21.17 ppm, while no toxicity appears in normal HEK293 cells. Mechanistically, the C5-AuNPs induced early apoptosis and inhibit cell-cycle progression at the stage of G0/G1. Collectively, these findings demonstrate that C. vulgaris-mediated AuNPs represent a promising preliminary in vitro findings for cancer therapy candidate.

Gold↗

Reactive oxygen species-independent G1 arrest induced by evening primrose extract in Ehrlich ascites tumor cells.

We previously demonstrated that evening primrose extract (EPE) induced apoptosis in Ehrlich ascites tumor cells (EATC), and this effect was specific on tumor cells. Furthermore, our results demonstrated that EPE exposure elicited a rapid increase in the activity of superoxide dismutase and intracellular peroxides levels. These changes caused translocation of Bax to mitochondria and a subsequent release of mitochondrial cytochrome c. However, no activation of caspase-3 was observed in EPE-treated EATC. On the other hand, apoptosis-inducing factor (AIF) was translocated from mitochondria to nuclei. The EPE-induced translocation of AIF was suppressed with the addition of catalase, suggesting that the rapid intracellular peroxide levels after addition of EPE triggers off induction of apoptosis, which is AIF-mediated and caspase-independent. In this study, we have shown that EPE elicited a dose-dependent accumulation of cells in the G1 phase and inhibited DNA synthesis. Our results also demonstrated that cell cycle arrest and inhibition of proliferation in EATC by EPE are associated with decreased Rb phosphorylation. Furthermore, inhibitions of Rb phosphorylation and DNA synthesis by EPE were not suppressed with the addition of catalase. The present study suggests that intracellular peroxides, which trigger off induction of apoptosis, are not the trigger of EPE-induced G1 arrest in cell cycle.

Animals↗

Obstetric cholestasis: outcome with active management.

OBJECTIVE: Conservative management of intrahepatic obstetric cholestasis is associated with a high stillbirth rate despite monitoring of fetal well-being with non-stress test and amniotic fluid volume assessment. Most cases of stillbirth are associated with meconium passage. We prospectively evaluated the effect of a management protocol inclusive of surveillance for presence of meconium and induction of labor at 37 weeks. STUDY DESIGN: Between January 1989 and December 1997, all women with obstetric cholestasis underwent transcervical amnioscopy after 36 weeks for assessment of amniotic fluid color, in addition to standard monitoring of fetal well-being (semi-weekly non-stress test and amniotic fluid volume determinations). Amniocentesis for fetal lung maturity and amniotic fluid color assessment was performed before 36 weeks in severe cases. Labor was induced at 37 weeks or earlier in the presence of non-reassuring fetal testing, meconium, or severe maternal symptoms unresponsive to therapy with mature fetal lungs. The obstetric outcome of the group with cholestasis was compared with that of the general obstetric population at our Institution during the study period. The rate of fetal death in the study group was compared with that of series published within the last 20 years, which used expectancy and conventional monitoring of fetal well-being. Statistical analysis utilized Fisher's exact test, Chi-square, and Student's t-test with P value <0.05 or an odds ratio (OR) with 95% confidence interval (CI) not inclusive of the unity considered significant. RESULTS: Obstetric cholestasis was diagnosed in 206/20,815 pregnant women (1%) at a median gestational age of 34 weeks (range 20-40). Delivery was prompted by non-reassuring fetal testing in four cases (2%). Meconium passage was documented in 33 cases (16%), in 11 of which before onset of labor and in 10 before 37 weeks. The rate of meconium passage before 37 weeks (17.9 versus 2.9%, OR=7.3; 95% CI 3.3, 16.0) was significantly higher in obstetric cholestasis than in the general obstetric population, whereas the cesarean section rate was similar in the two groups (15.1 versus 16.0%, OR=0.9; 95% CI 0.6, 1.4). The fetal death rate was significantly lower in the group managed with the current strategy than in the published series of obstetric cholestasis (0/218 versus 14/888, P=0.045). CONCLUSION: In pregnancies complicated by obstetric cholestasis, a protocol inclusive of search for meconium and elective delivery at 37 weeks, in addition to standard monitoring of fetal well-being, can significantly reduce the stillbirth rate without increasing the cesarean delivery rate.

Adult↗

Evaluation of the non-inferiority of a fixed combination of thyme fluid- and primrose root extract in comparison to a fixed combination of thyme fluid extract and primrose root tincture in patients with acute bronchitis. A single-blind, randomized, bi-centric clinical trial.

In a single-blind, randomized, bi-centric, prospective study, the non-inferiority of a fixed combination of thyme fluid extract and primrose root fluid extract (Bronchicum Elixir S, fluid test medication) was evaluated by comparison to a fixed combination of thyme fluid extract and primrose root tincture (Bronchcium Tropfen, drops test medication). The patients took either 6 x 5 ml of the fluid test medication (fluid group) or 5 x 1 ml of the drops test medication (drops group) daily. 189 outpatients (121 women, 68 men) suffering from acute, not previously treated bronchitis, lasting for less than 48 h, were randomized and treated with either fluid (94 patients: 66 women, 28 men) or drops (95 patients: 55 women, 40 men) over a time period of 7-9 days. 71 patients were excluded from the per-protocol (PP) collective because of violations regarding examination time points and/or intake of the study medication. The primary outcome criterion was to demonstrate the non-inferiority of the Score (BSS) at the end of the study compared to baseline. In the fluid group, the BSS decreased from 11.0 +/- 5.0 points at baseline to 2.6 +/- 4.6 (76%) at study end compared to a decrease from 11.0 +/- 4.8 points at baseline to 2.5 +/- 4.2 (77.1%) at study end in the drops group (Intention-to-treat (ITT) -analysis). The decrease of the BSS in both groups was highly significant (p < or = 10(-3)), but there was no difference between the two groups. Differences between the study sites were noticed regarding the baseline BSS, which were twice as high at study site 2 compared to study site 1 (probably due to the different way the patients were recruited). However, a statistically significant intergroup difference was not observed at any time point. At the end of the study, 52.1% of the patients of the fluid group were symptom free and 53.7% of the patients from the drops group were symptom free as compared by the ITT-analysis (secondary outcome criterion). For both parameters, the PP-analysis support the non-inferiority of the fluid compared to the drops. The global therapeutic efficacy of the fluid as well as of the drops was rated as being "very good" or "good" by 80% of the patients and clinical investigators. The tolerability was very good in both groups; neither serious adverse events nor clinically relevant findings in the safety parameters were observed. A total of 10 adverse events occurred, 5 in the fluid group and 5 in the drops group. Five of these adverse events (2 in the fluid group and 3 in the drops group) were considered to be possibly or probably related to the intake of the study medication. Neither serious nor unknown adverse drug reactions were observed. One drop-out occurred during the study, because of ineffectiveness of the study medication. In the global safety assessment, the tolerability of both medications was rated by about 90% of the patients and by clinical investigators as "good" or "very good". The study demonstrated that the fixed combination of thyme fluid extract and primrose root extract and the combination of thyme fluid extract and primrose root tincture were well tolerated and showed comparable results regarding their efficacy, e.g. decrease of the bronchitis symptoms (primary outcome criterion) and in relief of symptoms (secondary outcome criterion). The results of the study confirm the non-inferiority of the fluid, a combination of thyme fluid extract and primrose root extract when compared to the drops, a combination of thyme fluid extract and primrose root tincture.

Adult↗

Efficacy and tolerability of a fixed combination of thyme and primrose root in patients with acute bronchitis. A double-blind, randomized, placebo-controlled clinical trial.

In a double-blind, randomized, placebo-controlled, multicenter, prospective study, the clinical efficacy and tolerability of a fixed combination of thyme fluid extract and primose root tincture (Bronchicum Tropfen) was investigated at a dosage of 30 drops (1 ml), taken orally five times daily. 150 outpatients (97 women, 53 men) suffering from acute, not previously treated bronchitis, lasting for less than 48 h, were randomized and treated with either verum (75 patients: 45 women, 30 men) or placebo (75 patients: 52 women, 23 men) over a time period of 7-9 days. 17 patients were excluded from the per-protocol (PP) collective because of either withdrawal from the trial (n = 2) or violations regarding examination time points and/or intake of the study medication (n = 15). The primary outcome criterion for efficacy assessment was the decrease of the Bronchitis Severity Score (BSS) at the end of the study compared to baseline. In the verum group, the BSS decreased from 12.0 +/- 4.4 points at baseline to 1.0 +/- 2.1 at study end compared to a decrease from 11.7 +/- 4.3 points at baseline to 6.5 +/- 4.8 at study end in the placebo group. The inter-group difference of 5.8 points was highly significant (p < or = 10(-3)) in favour of the verum medication [Intention-to-treat (ITT) analysis]. At the end of the study, significantly more patients were symptom free in the verum group (58.7%) than in the placebo group (5.3%) as compared by the ITT analysis (secondary outcome criterion). For both parameters, the PP analysis showed comparable results. The results for the concomitant variables of efficacy support the high superiority of the verum medication compared to placebo. The therapeutic effect was more pronounced the stronger the severity of the acute bronchitis was (as proofed by a stratified evaluation based on severity grade). The tolerability was very good in both groups; neither serious adverse events nor clinically relevant findings in the safety parameters were observed. A total of 7 adverse events occurred, 2 in the verum group and 5 in the placebo group. One of the two adverse events in the verum group was considered to be possibly related to the intake of the study medication. Neither serious nor unknown adverse drug reactions were observed. Two drop-outs occurred during the study related to adverse events, both in the placebo group. In the global safety assessment, the tolerability of both medications was rated as "good" or "very good" by more than 90% of the patients and physicians. In the present study, the fixed combination of thyme fluid extract and primrose root tincture was well tolerated and resulted in a clinically relevant and more pronounced decrease of the bronchitis symptoms (primary outcome criterion) and in shortening the duration of acute bronchitis (secondary outcome criterion) when compared to placebo.

Acute Disease↗

Population growth rates: issues and an application.

Current issues in population dynamics are discussed in the context of The Royal Society Discussion Meeting 'Population growth rate: determining factors and role in population regulation'. In particular, different views on the centrality of population growth rates to the study of population dynamics and the role of experiments and theory are explored. Major themes emerging include the role of modern statistical techniques in bringing together experimental and theoretical studies, the importance of long-term experimentation and the need for ecology to have model systems, and the value of population growth rate as a means of understanding and predicting population change. The last point is illustrated by the application of a recently introduced technique, integral projection modelling, to study the population growth rate of a monocarpic perennial plant, its elasticities to different life-history components and the evolution of an evolutionarily stable strategy size at flowering.

Biological Evolution↗

Systemic availability and pharmacokinetics of thymol in humans.

Essential oil compounds such as found in thyme extract are established for the therapy of chronic and acute bronchitis. Various pharmacodynamic activities for thyme extract and the essential thyme oil, respectively, have been demonstrated in vitro, but availability of these compounds in the respective target organs has not been proven. Thus, investigation of absorption, distribution, metabolism, and excretion are necessary to provide the link between in vitro effects and in vivo studies. To determine the systemic availability and the pharmacokinetics of thymol after oral application to humans, a clinical trial was carried out in 12 healthy volunteers. Each subject received a single dose of a Bronchipret TP tablet, which is equivalent to 1.08 mg thymol. No thymol could be detected in plasma or urine. However, the metabolites thymol sulfate and thymol glucuronide were found in urine and identified by LC-MS/MS. Plasma and urine samples were analyzed after enzymatic hydrolysis of the metabolites by headspace solid-phase microextraction prior to GC analysis and flame ionization detection. Thymol sulfate, but not thymol glucuronide, was detectable in plasma. Peak plasma concentrations were 93.1+/-24.5 ng ml(-1) and were reached after 2.0+/-0.8 hours. The mean terminal elimination half-life was 10.2 hours. Thymol sulfate was detectable up to 41 hours after administration. Urinary excretion could be followed over 24 hours. The amount of both thymol sulfate and glucuronide excreted in 24-hour urine was 16.2%+/-4.5% of the dose.

Administration, Oral↗

Effects of an anthroposophical remedy on cardiorespiratory regulation.

CONTEXT: The human organism has the inherent ability to regulate and coordinate physiological functions to establish well-being. If this ability is disturbed, eg, in cases of orthostatic syndrome with purely functional disorders, an herbal remedy based on anthroposophical medicine may be able to regulate such rhythmic disturbances. OBJECTIVE: To determine the effect of the anthroposophical herbal remedy on stimulating the ability to regulate and coordinate physiological functions in healthy subjects. DESIGN: Double-blind, placebo-controlled, randomized trial PARTICIPANTS: Ninety-nine healthy subjects; 49 received the remedy, 50 received the placebo. INTERVENTION: Oral administration of the remedy for 4 weeks, 20 drops 4 times daily. MAIN OUTCOME MEASURES: Cardiorespiratory interaction was analyzed by 2 measures: the heart-respiratory ratio and the phase-coordination ratio of heartbeat and respiration. They were calculated from heart rate and respiratory rate, which were derived from 24-hour electrocardiogram recordings before and after the administration of the remedy. Improved normalization of these measures during nighttime sleep after administration of the remedy indicates a stimulation of regulation. RESULTS: Oral administration of the remedy resulted in an improved normalization of heart-respiratory ratio, phase-coordination ratio and heart rate during nighttime sleep. These results were not observed in the placebo group. CONCLUSIONS: The remedy stimulates the regulation of cardiorespiratory interaction during nighttime sleep. Furthermore, improved normalization indicates a general improvement of the regulatory processes of functional rhythms.

Adult↗

[Production of galenic preparations from primrose].

Pharmaceutical herbal preparations have been used for the treatment of respiratory diseases for a long time. Alongside with the well known herbs, there are many of crude drugs to be investigated and applied in therapeutics. Respiratory diseases are mainly treated by chemical medicines and antibiotics. The use of herbal preparations is limited and they are usually used as supplemental ones. Application of modern research techniques, the new data on biochemical processes in plants, chemical compounds and information on their value in therapy were obtained. The pharmacological effect of the compounds could be foreseen from their chemical structure. The development of rational technology of pharmaceutical preparations follows the identification of active constituents in pharmaceutical herbs. The proper use of pharmaceutical herbs supplies the organism with the natural substances, thus preventing various diseases. The primrose dried raw material for use in production of pharmaceutical preparations has been analyzed and its quality was evaluated. The dry primrose extract was produced and tested, and later it was used in development of pharmaceutical preparations. The liquid primrose extract and two compositions of primrose syrup were developed. The stability of experimental preparations was evaluated.

Chromatography↗