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At least 739 records · Page 41Linked to original sources
PubMed1998

Influence of genuine kavapyrone enantiomers on the GABA-A binding site.

The influence of kavapyrones from Piper methysticum Forst. on the GABAA receptor was demonstrated using radioreceptor assays. Both the dienolide yangonin and the genuine enolide enantiomers (+)-kavain, (+)-dihydrokavain, (+)-methysticin, and (+)-dihydromethysticin enhanced the specific binding of [3H]bicuculline methochloride ([3H]BMC). The kavapyrones have been investigated at assay concentrations between 100 microM and 10 nM. (+)-Kavain, (+)-methysticin and (+)-dihydromethysticin showed maximal enhancements of 18% to 28% at a concentration of 0.1 microM, whereas a 100-fold concentration of (+)-dihydrokavain revealed a similar modulatory activity of 22%. In the presence of 1 microM yangonin an increase of about 21% of the specific [3H]BMC binding was observed. Desmethoxyyangonin did not alter the binding behavior of the GABAA-receptor. A structure comparison of desmethoxyyangonin and yangonin indicated that the aromatic methoxy group was of particular importance for the modulatory activity. In contrast, the substitution pattern of the aromatic ring did not influence the modulatory activity of the enolides in a decisive manner. A structure comparison of desmethoxyyangonin and (+)-kavain revealed that an angular lactone ring was an important structure requirement. Both the enolides and the dienolides did not inhibit the specific binding of [3H]flunitrazepan. Thus, the influence on the GABAA receptor was not based upon an interaction of these kavapyrones with the benzodiazepine receptor.

Animals↗
PubMed1997

Relaxation of evoked contractile activity of isolated guinea-pig ileum by (+/-)-kavain.

Kava pyrones are the pharmacologically active compounds of Piper methysticum Forst. In the present study, the effect of the synthetic kava pyrone (+/-)-kavain was investigated on evoked contractile activity of isolated guinea-pig ileum. (+/-)-Kavain (1 microM-1 mM) dose-dependently reduced contractions of ileum evoked by carbachol (10 microM), by BAY K 8644 (0.3 microM), or by substance P (0.05 microM). (+/-)-Kavain also inhibited the contractile responses induced by raising the extracellular K+ concentration from 4 to 20 mM and by blocking the K+ channel by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After pre-incubation with 1 microM nifedipine, carbachol (1 microM) evoked 18.2 +/- 14.3% of contraction at control (i.e. prior pre-incubation with nifedipine). This remaining response was completely abolished by high concentrations of (+/-)-kavain (400 microM). After treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol (1 microM) evoked 27.0 +/- 6.2% of the control response in untreated ileum. These contractions were also blocked by (+/-)-kavain (400 microM). However, (+/-)-kavain had no effect on the caffeine-induced (20 mM) contractions of ileum strips, which were permeabilized with digitonin or beta-escin. Moreover, it failed to affect Ca(2+)-evoked contractions of skinned muscles. These results suggest that the kava pyrone (+/-)-kavain may act in a non-specific musculotropic way on the smooth muscle membrane.

Animals↗
PubMed1997

[Eye symptoms in Schimmelpenning-Feuerstein-Mims syndrome, a rare phacomatosis].

BACKGROUND: Children with connatal malformations of the face and of the eyes may run a long diagnostic and narrow therapeutic way. By an early diagnosis, this procedure could become significantly shorter und much easier. PATIENTS HISTOPATHOLOGY: Three clinical observations give typical examples: In correlation to the history of a patient described in 1975 by Meythaler (18) we examined two babies with naevus sebaceus Jadassohn, colobomas of the lids, epibulbar tumors, microphthalmus, and white, vascularized corneal opacifications. Already at the age of four weeks we were able to confirm the diagnosis and documented our findings in anesthesia by tables, photographs, and histopathologic observations. FINDINGS: Localisations and expression of the symptoms are very different in patient 2 and 3. In patient 2 the lid hamartoma contained lacrimal gland, cartilage and bone structures. Reconstructive lid operations corrected the lid function and resulted in esthetic amelioration. CONCLUSIONS: The important points in our casuistics were: 1. After comparison of our findings with those in literature, there was not found any other patient with scalp defect as shown in patient 2. A cataract as described by Piper (21) was not seen in any of our patients; as supposed by the author, it should be due to cortisone application. 3. As Jadassohnnaevus may develop basalioma or adenocarcinoma, further dermatologic survey is indicated. 4. So long, no neurologic symptoms have occurred.

Cataract↗
PubMed1983

Environmental controls on stomatal conductance in a shrub of the humid tropics.

Leaves of Piper hispidum, a shrub native to the lowland tropics of Mexico, have a strong stomatal response to humidity that results in similar rates of water loss under a wide range of leaf-to-air water-vapor concentration gradients. Stomatal conductance of these leaves is insensitive to CO(2) concentration and increases in response to high humidity even in the dark.

Journal Article↗
PubMed2002

Modulation of the catalytic activity of neutrophil collagenase MMP-8 on bovine collagen I. Role of the activation cleavage and of the hemopexin-like domain.

The cleavage of bovine collagen I by neutrophil collagenase MMP-8 has been followed at pH 7.4, 37 degrees C. The behavior of the whole enzyme molecule (whMMP-8), displaying both the catalytic domain and the hemopexin-like domain, has been compared under the same experimental conditions with that of the catalytic domain only. The main observation is that whMMP-8 cleaves bovine collagen I only at a single specific site, as already reported by many others (Mallya, S. K., Mookhtiar, K. A., Gao, Y., Brew, K., Dioszegi, M., Birkedal-Hansen, H., and van Wart, H. E. (1990) Biochemistry 29, 10628-10634; Knäuper, V., Osthues, A., DeClerk, Y. A., Langley, K. A., Bläser, J., and Tschesche, H. (1993) Biochem. J. 291, 847-854; Marini, S., Fasciglione, G. F., De Sanctis, G., D'Alessio, S., Politi, V., and Coletta, M. (2000) J. Biol. Chem. 275, 18657-18663), whereas the catalytic domain lacks this specificity and cleaves the collagen molecule at multiple sites. Furthermore, a meaningful difference is observed for the cleavage features displayed by two forms of the catalytic domain, which differ for the N terminus resulting from the activation process (i.e. the former Met(80) of the proenzyme (MetMMP-8) and the former Phe(79) of the proenzyme (PheMMP-8)). Thus, the PheMMP-8 species is characterized by a much faster k(cat)/K(m), fully attributable to a lower K(m), suggesting that the conformation of the catalytic domain, induced by the insertion of this N-terminal residue in a specific pocket (Reinemer, P., Grams, F., Huber, R., Kleine, T., Schnierer, S., Piper, M., Tschesche, H., and Bode, W. (1994) FEBS Lett. 338, 227-233), brings about a better, although less discriminatory, recognition process of cleavage site(s) on bovine collagen I.

Animals↗
PubMed2001

Comparative study of the assay of Artemia salina L. and the estimate of the medium lethal dose (LD50 value) in mice, to determine oral acute toxicity of plant extracts.

Artemia salina L. (Artemiidae), the brine shrimp larva, is an invertebrate used in the alternative test to determine toxicity of chemical and natural products. In this study the Medium Lethal Concentrations (LC50 value) of 20 plant extracts, Aloe vera (L.) Burm. F. (Aloeaceae), Artemisia absinthium L. (Asteraceae); Citrus aurantium L. (Rutaceae); Cymbopogon citratus (DC. Ex Nees) Stapf (Poaceae); Datura stramonium L. (Solanaceae); Justicia pectoralis Jacq. (Acanthaceae); Musa x paradisiaca L. (Musaceae); Ocimum basilicum L.; O. gratissimum L.; O. tenuiflorum L. (Lamiaceae); Pimenta dioica (L.) Merr. (Myrtaceae); Piper auritum Kunth (Piperaceae); Plantago major L. (Plantaginaceae); Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae); Ruta graveolens L. (Rutaceae); Senna alata (L.) Roxb. (Fabaceae); Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae); and Thuja occidentalis L. (Cupressaceae), were determined using Artemia salina L. (Artemiidae), with the objective of relating the results to the LD50 values reported in mice (tested at three concentrations: 10, 100, and 1000 microg/mL, for each extract). We found good correlation between the in vivo and the in vitro tests (r = 0.85 p < 0.05), and this method is a useful tool for predicting oral acute toxicity in plant extracts.

Animals↗
PubMed2001

Synergy and other interactions in phytomedicines.

Synergistic interactions are of vital importance in phytomedicines, to explain difficulties in always isolating a single active ingredient, and explain the efficacy of apparently low doses of active constituents in a herbal product. This concept, that a whole or partially purified extract of a plant offers advantages over a single isolated ingredient, also underpins the philosophy of herbal medicine. Evidence to support the occurrence of synergy in within phytomedicines is now accumulating and is reviewed here. Synergistic interactions are documented for constituents within a total extract of a single herb, as well as between different herbs in a formulation. Positive and negative aspects of interactions are discussed together with the methods used to identify and measure synergy. The evidence is divided into experimental, in vitro instances, as well as clinical examples where available. Herbs discussed include Ginkgo biloba, Piper methysticum (Kava-Kava), Glycyrrhiza glabra, Hypericum perforatum, Valeriana officinalis, Cannabis sativa, Salix alba and others.

Cannabis↗
PubMed2003

Quality aspects of traditional and industrial Kava-extracts.

An aqueous decoction of Piper methysticum has been used since centuries of Pacific Island at social religious-ceremonial and social events without hepatotoxic side effects in contrast to the speculation on industrial Kava preparations. It was assumed that the traditional non-alcoholic drink contains a spectrum of other constituents compared to the acetonic and ethanolic extracts. The TLC-analysis demonstrates, however, that under qualitative aspects there is no difference between aqueous and acetonic and ethanolic extracts respectively.

Chromatography, Thin Layer↗
PubMed1994

Characteristics of patients who choose between two types of group psychotherapy.

Patient selection or matching to group psychotherapy is usually done by therapists. An alternative is to allow patients to "sample" and then select from different group therapies. In the current study characteristics of patients (N = 20) who selected from two types of group psychotherapy in a day-treatment program were examined. Patients were assessed on measures of current psychiatric symptomatology (Symptom Checklist 90-Revised [SCL-90R]; Derogatis, Rickles & Rock, 1976), psychological mindedness (McCallum & Piper, 1990) and psychological defenses Mechanisms Inventory (Ihilevich & Gleser, 1986). The two groups did not differ with regard to symptomatology or psychological mindedness. It was found that patients who chose a verbal and process-oriented psychotherapy tended to have externalizing defenses (turning anger against others and projection), however. These defenses appear to be congruent with this more emotionally expressive therapy. Patients who chose a structured and activity-oriented group psychotherapy tended to have internalizing defenses (repression/denial and intellectualization). These defenses seem consistent with this group therapy, which emphasized less emotional expressiveness. The implications of patient choice for group therapy and patient selection practices are discussed.

Adult↗
PubMed2001

Dietary and supplement treatment of iron deficiency results in improvements in general health and fatigue in Australian women of childbearing age.

OBJECTIVE: To examine the effects of iron deficiency and its treatment by iron supplementation or a high iron diet on fatigue and general health measures in women of childbearing age. DESIGN: Randomised controlled trial to compare supplement and dietary treatment of iron deficiency. SUBJECTS: 44 iron deficient (serum ferritin < 15 microg/L or serum ferritin 15-20 microg/L, plus two of the following: serum iron < 10 micromol/L, total iron binding capacity > 68 micromol/L or transferrin saturation < 15%) and 22 iron replete (hemoglobin > or = 10 g/L and serum ferritin > 20 microg/L) women 18 to 50 years of age were matched for age and parity. INTERVENTIONS: Iron deficient women were randomly allocated to either iron supplementation or a high iron diet for 12 weeks. MEASURES OF OUTCOME: Iron deficient and iron replete participants had iron studies performed and completed the Piper Fatigue Scale (PFS) and the SF-36 general health and well-being questionnaire at baseline (T0), following the 12 week intervention (T1) and again after a six-month non-intervention phase (T2). The SF-36 includes measures of physical (PCS) and mental (MCS) health and vitality (VT). RESULTS: MCS and VT scores were lower and PFS scores were higher for iron deficient women (diet and supplement groups) than iron replete women at baseline. Both intervention groups showed similar improvements in MCS, VT and PFS scores during the intervention phase, but mean increases in serum ferritin were greater in the supplement than the diet group. PCS scores were not related to iron status. CONCLUSIONS: Treatment of iron deficiency with either supplementation or a high iron diet results in improved mental health and decreased fatigue among women of childbearing age.

Adolescent↗
PubMed1997

Acute effects of kava, alone or in combination with alcohol, on subjective measures of impairment and intoxication and on cognitive performance.

Kava (Piper methysticum) and alcohol were administered either separately or in combination to human subjects. Self-reports of their levels of impairment and intoxication were collected, and performance skills on a number of cognitive and visuomotor tests were determined, before and three times after consumption of the experimental drink. Kava alone had no effect on reported condition. In contrast, alcohol produced marked changes in each of the five subjective measures, all of which were in the direction of lowered ability. The combination of these two substances produced even larger negative changes on these measures. In the cognitive tests, kava produced a decrement in performance on Digit Symbol Coding. Alcohol produced a significant decrease in performance on a divided attention test, which was almost entirely on the peripheral, discontinuous component of the test. The combination of kava and alcohol produced an even greater decrease in performance on this test, and in the same component. The present findings suggest that kava alone has little effect on reported condition and cognitive performance, but appears to potentiate both perceived and measured impairment when combined with alcohol.

Journal Article↗
PubMed2002

Hydroxyl radical formation and oxidative DNA damage induced by areca quid in vivo.

Chewing areca quid (AQ) has been implicated as a major risk factor for the development of oral squamous-cell carcinoma (OSCC). Recent studies have suggested that AQ-generated reactive oxygen species (ROS) is one of the contributing factors for oral carcinogenesis. However, the AQ used in Taiwan is different from that used in other countries. This study is designed to test whether ROS are generated and the consequent effects in locally prepared AQ in vivo. We measured the hydroxyl radical formation, as represented by the presence of o- and m-tyrosine in saliva from volunteers who chewed AQ containing 20 mg phenylalanine. Their saliva contained significantly higher amounts (p < .05) of o- and m-tyrosine as compared to the controls. In addition, chewing AQ containing Piper betle inflorescence generated higher amounts of m-tyrosine, but not o-tyrosine, in saliva than did chewing AQ containing betel leaf. We further tested the oxidative DNA damaging effect of the reconstituted AQ, as evidenced by the elevation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels, in hamster buccal pouch. Following daily painting for 14 d, the 8-OH-dG level in hamster buccal pouch is significantly elevated (p < .05) in the AQ-treated group versus the controls. These findings demonstrate that ROS, such as hydroxyl radical, are formed in the human oral cavity during AQ chewing, and chewing such prepared AQ might cause oxidative DNA damage to the surrounding tissues.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Acute hepatitis induced by kava kava.

BACKGROUND: Herbal preparations are available widely and regarded generally by the public as harmless remedies for a variety of medical ailments. We report a case of acute hepatitis associated with the use of kava kava, derived from the root of the pepper plant, Piper methysticum. It is used in the United States as an antianxiety and sedative agent. CASE REPORT: A previously healthy 14-year-old female was admitted to the hospital with hepatic failure. Initial therapy, including plasmapheresis, was unsuccessful and she deteriorated. She ultimately required a liver transplant and now remains well. The liver biopsy showed hepatocellular necrosis consistent with chemical hepatitis. A work-up for alternative causes of liver failure was negative. The patient gave a history of taking a kava kava-containing product for four months. The use of kava kava and liver failure, is supported by kava kava use, a negative work-up for alternative causes of liver failure, and histological changes in the liver. CONCLUSIONS: Health care professionals need to be aware of the possibility of kava kava-induced hepatotoxicity. The toxicity of these alternative remedies emphasizes the importance of surveillance programs and quality control in the manufacture of these products. Clinicians must remain aware of the toxic potential of herbal products and always inquire about their intake in cases of unexplained liver injury.

Adolescent↗
PubMed1994

The amino terminus of GLUT4 functions as an internalization motif but not an intracellular retention signal when substituted for the transferrin receptor cytoplasmic domain.

Previous studies have demonstrated that the amino-terminal cytoplasmic domain of GLUT4 contains a phenylalanine-based targeting motif that determines its steady state distribution between the surface and the interior of cells (Piper, R. C., C. Tai, P. Kuleza, S. Pang, D. Warnock, J. Baenziger, J. W. Slot, H. J. Geuze, C. Puri, and D. E. James. 1993. J. Cell Biol. 121:1221). To directly measure the effect that the GLUT4 amino terminus has on internalization and subsequent recycling back to the cell surface, we constructed chimeras in which this sequence was substituted for the amino-terminal cytoplasmic domain of the human transferrin receptor. The chimeras were stably transfected into Chinese hamster ovary cells and their endocytic behavior characterized. The GLUT4-transferrin receptor chimera was recycled back to the cell surface with a rate similar to the transferrin receptor, indicating that the GLUT4 sequence was not promoting intracellular retention of the chimera. The GLUT4-transferrin receptor chimera was internalized at half the rate of the transferrin receptor. Substitution of an alanine for phenylalanine at position 5 slowed internalization of the chimera by twofold, to a level characteristic of bulk membrane internalization. However, substitution of a tyrosine increased the rate of internalization to the level of the transferrin receptor. Neither of these substitutions significantly altered the rate at which the chimeras were recycled back to the cell surface. These results demonstrate that the major function of the GLUT4 amino-terminal domain is to promote the effective internalization of the protein from the cell surface, via a functional phenylalanine-based internalization motif, rather than retention of the transporter within intracellular structures.

Amino Acid Sequence↗
PubMed2004

Gating charges in the activation and inactivation processes of the HERG channel.

The hERG channel has a relatively slow activation process but an extremely fast and voltage-sensitive inactivation process. Direct measurement of hERG's gating current (Piper, D.R., A. Varghese, M.C. Sanguinetti, and M. Tristani-Firouzi. 2003. PNAS. 100:10534-10539) reveals two kinetic components of gating charge transfer that may originate from two channel domains. This study is designed to address three questions: (1) which of the six positive charges in hERG's major voltage sensor, S4, are responsible for gating charge transfer during activation, (2) whether a negative charge in the cytoplasmic half of S2 (D466) also contributes to gating charge transfer, and (3) whether S4 serves as the sole voltage sensor for hERG inactivation. We individually mutate S4's positive charges and D466 to cysteine, and examine (a) effects of mutations on the number of equivalent gating charges transferred during activation (z(a)) and inactivation (z(i)), and (b) sidedness and state dependence of accessibility of introduced cysteine side chains to a membrane-impermeable thiol-modifying reagent (MTSET). Neutralizing the outer three positive charges in S4 and D466 in S2 reduces z(a), and cysteine side chains introduced into these positions experience state-dependent changes in MTSET accessibility. On the other hand, neutralizing the inner three positive charges in S4 does not affect z(a). None of the charge mutations affect z(i). We propose that the scheme of gating charge transfer during hERG's activation process is similar to that described for the Shaker channel, although hERG has less gating charge in its S4 than in Shaker. Furthermore, channel domain other than S4 contributes to gating charge involved in hERG's inactivation process.

Amino Acid Substitution↗
PubMed2002

Kava--the unfolding story: report on a work-in-progress.

This paper, originated as a submission (now updated) to the U.K. Medicines Control Agency and Committee of Safety of Medicines (CSM) on January 11, 2002, in response to a report circulated by the German Federal Institute for Drugs and Medical Products (German initials are BfArM), a compilation of which is summarized in Appendix 2. This agency issued notification in late November 2001 of some thirty adverse events associated with the use of concentrated standardized preparations of kava (Piper methysticum, Forst. f.) reported from Germany and Switzerland. An analysis of the summary of the BfArM case reports (see Appendix 2) shows that these contain duplications among the cases cited. The original submission that was sent to the CSM January 2002 has been updated to the version published here. This new version was completed in April 2002. As a result of the alert from BfArM, the evaluation of kava's safety is now occurring on a worldwide basis and, being that this a matter of considerable importance to the public, the health care community, and regulatory authorities as well as to kava farmers throughout Polynesia, it is it important to depict this progress report. As such, this updated report does not provide final answers. The material released by the BfArM is lacking in detail; however, it is hoped that this report will shed light on the kava controversy. It is anticipated that there will be further updates shortly. This report, prepared on behalf of the Traditional Medicines Evaluation Committee, a subcommittee of the European Herbal Practitioners Association, argues that many of the adverse events cited by the BfArM should not be attributed to kava. In addition, the report states that the properties of concentrated standardized kava extracts - as opposed to preparations that closely approximate those created for traditional use - contribute to causing adverse events. This report proposes a number of simple measures that will ensure that safe kava preparations may continue to be available in the United Kingdom.

Adverse Drug Reaction Reporting Systems↗
PubMed2003

Virtual reality intervention for older women with breast cancer.

This study examined the effects of a virtual reality distraction intervention on chemotherapy-related symptom distress levels in 16 women aged 50 and older. A cross-over design was used to answer the following research questions: (1) Is virtual reality an effective distraction intervention for reducing chemotherapy-related symptom distress levels in older women with breast cancer? (2) Does virtual reality have a lasting effect? Chemotherapy treatments are intensive and difficult to endure. One way to cope with chemotherapy-related symptom distress is through the use of distraction. For this study, a head-mounted display (Sony PC Glasstron PLM - S700) was used to display encompassing images and block competing stimuli during chemotherapy infusions. The Symptom Distress Scale (SDS), Revised Piper Fatigue Scale (PFS), and the State Anxiety Inventory (SAI) were used to measure symptom distress. For two matched chemotherapy treatments, one pre-test and two post-test measures were employed. Participants were randomly assigned to receive the VR distraction intervention during one chemotherapy treatment and received no distraction intervention (control condition) during an alternate chemotherapy treatment. Analysis using paired t-tests demonstrated a significant decrease in the SAI (p = 0.10) scores immediately following chemotherapy treatments when participants used VR. No significant changes were found in SDS or PFS values. There was a consistent trend toward improved symptoms on all measures 48 h following completion of chemotherapy. Evaluation of the intervention indicated that women thought the head mounted device was easy to use, they experienced no cybersickness, and 100% would use VR again.

Adaptation, Psychological↗
PubMed1999

Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history.

Betel quid (BQ) chewing has been associated with an increased risk of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). Piper betel inflorescence, which contains 15 mg/g safrole, is a unique ingredient of BQ in Taiwan. Chewing such prepared BQ may contribute to safrole exposure in human beings (420 microM safrole in saliva). Safrole is a known rodent hepatocarcinogen, yet its carcinogenicity in human beings is largely undetermined. In this study, using a (32)P-post-labeling method, we have found a high frequency of safrole-like DNA adducts in BQ-associated OSCC (77%, 23/30) and non-cancerous matched tissue (NCMT) (97%, 29/30). This was in contrast to the absence (< 1/10(9) nucleotides) of such adducts in all of non-BQ-associated OSCC and their paired NCMT (P < 0.001). Six of seven OSF also exhibited the same safrole-like DNA adduct. The DNA adduct levels in OSF and NCMT were significantly higher than in OSCC (P < 0.05). Using co-chromatography and rechromatography techniques, we further demonstrated that these adducts were identical to synthetic safrole-dGMP adducts as well as DNA adducts from 1'-hydroxysafrole-treated HepG2 cells. These results suggest that safrole forms stable safrole-DNA adducts in human oral tissue following BQ chewing, which may contribute to oral carcinogenesis.

Areca↗