Intraspecific variation in morphology of spiny pollen grains along an altitudinal gradient in an insect-pollinated shrub.

Intraspecific variations in pollen morphological traits are poorly studied. Interspecific variations are often associated with pollination systems and pollinator types. Altitudinal environmental changes, which can influence local pollinator assemblages, provide opportunities to explore differentiation in pollen traits of a single species over short distances. The aim of this study is to examine intraspecific variations in pollen traits of an insect-pollinated shrub, Weigela hortensis (Caprifoliaceae), along an altitudinal gradient. Pollen spine phenotypes (length, number and density), pollen diameter, lipid mass (pollenkitt) around pollen grains, pollen production per flower and pollinator assemblages were compared at four sites at different altitudes. Spine length and the spine length/diameter ratio of pollen grains were greater at higher altitudes but not correlated with flower or plant size. Spine number and density increased as flower size increased, and pollen lipid mass decreased as plant size increased. Bees were the predominant pollinators at low-altitude sites whereas flies, specifically Oligoneura spp. (Acroceridae), increased in relative abundance with increasing altitude. The results of this study suggest that the increase in spine length with altitude was the result of selection favouring longer spines at higher-altitude sites and/or shorter spines at lower-altitude sites. The altitudinal variation in selection pressure on spine length could reflect changes in local pollinator assemblages with altitude.

Unconventional High-Energy-State Contribution to the Cooper Pairing in the Underdoped Copper-Oxide Superconductor HgBa_{2}Ca_{2}Cu_{3}O_{8+δ}.

We study the temperature-dependent electronic B_{1g} Raman response of a slightly underdoped single crystal HgBa_{2}Ca_{2}Cu_{3}O_{8+δ} with a superconducting critical temperature T_{c}=122 K. Our main finding is that the superconducting pair-breaking peak is associated with a dip on its higher-energy side, disappearing together at T_{c}. This result reveals a key aspect of the unconventional pairing mechanism: spectral weight lost in the dip is transferred to the pair-breaking peak at lower energies. This conclusion is supported by cellular dynamical mean-field theory on the Hubbard model, which is able to reproduce all the main features of the B_{1g} Raman response and explain the peak-dip behavior in terms of a nontrivial relationship between the superconducting gap and the pseudogap.

Effects of compression at myofascial trigger points in patients with acute low back pain: A randomized controlled trial.

BACKGROUND: Although there is some evidence that massage therapy, especially compression at myofascial trigger points (MTrPs), is effective for sub-acute and chronic low back pain, the effectiveness of massage therapy with compression at MTrPs for acute low back pain has not been studied. METHODS: To evaluate the effectiveness of compression at MTrPs for acute low back pain, 63 patients with acute low back pain were randomly assigned to one of three groups: the MTrP group who received compression at MTrPs (N = 23), the non-MTrP group who received compression at non-trigger points (N = 21), and the effleurage massage group who received superficial massage (N = 19). The patients received the assigned treatment 3 times/week for 2 weeks. The subjective pain intensity in static and dynamic conditions and disability caused by low back pain were measured by the visual analogue scale (VAS) and Roland-Morris questionnaire (RMQ), respectively; along with the range of motion (ROM) at the lumbar region and pressure pain threshold (PPT) at trigger points before treatment (baseline), 1 week after the start of treatment, and 1 month after the end of treatment (follow-up). RESULTS: Static and dynamic VAS score, PPT and ROM were significantly improved in the MTrP group compared with those in the non-MTrP and effleurage groups. CONCLUSIONS: These results indicate that compression at MTrPs is effective to treat acute low back pain compared with compression at non-MTrPs and superficial massage. For this article, a commentary is available at the Wiley Online Library.

In vivo approach for the evaluation of mechanism-based inhibition of cytochrome P450 3A in rats.

1. There have been no reports showing that the area under the concentration-time curve (AUC) of a probe drug is elevated due to mechanism-based inhibition (MBI) of drug-metabolizing enzymes in animals. This study ascertained that mechanism-based inhibitors reported to induce drug-drug interactions (DDIs) in humans also caused MBI in rats. 2. Midazolam (MDZ), mainly metabolized by cytochrome P450 3A in rats, and mibefradil, which showed the most intense time-dependent inhibition among the inhibitors tested, were selected as the probe and the inhibitor, respectively. Following pretreatment of mibefradil at 24 h before MDZ administration in rats, the C(max) and AUC values of MDZ were significantly elevated in comparison with the control. The free plasma concentration of mibefradil was substantially lower than the IC(50) value observed in the in vitro inhibition study, suggesting that the DDI was due to MBI. 3. It is concluded that the evaluation of MBI in rats in vivo in combination with in vitro data using human enzymes could be useful to evaluate risk in clinical studies.

Strengthening emergency obstetric care in Nepal: The Women's Right to Life and Health Project (WRLHP).

INTRODUCTION: The Women's Right to Life and Health Project contributes to Nepal's National Safe Motherhood Program and maternal mortality reduction efforts by working to improve the availability, quality and utilization of emergency obstetric care services in public health facilities. METHODS: The project upgraded 8 existing public health facilities through infrastructure, equipment, training, data collection, policy advocacy, and community information activities. The total cost of the project was approximately US$1.6 million. RESULTS: In 5 years, 3 comprehensive and 4 basic emergency obstetric care (EmOC) facilities were established in an area where adequate EmOC services were previously lacking. From 2000 to 2004, met need for EmOC improved from 1.9 to 16.9%; the proportion of births in EmOC project facilities increased from 3.8 to 8.3%; and the case fatality rate declined from 2.7 to 0.3%. DISCUSSION: While the use of maternity services is still low in Nepal, improving availability and quality of EmOC together with community empowerment can increase utilization by women with complications, even in low-resource settings. Partnerships with government and donors were key to the project's success. Similar efforts should be replicated throughout Nepal to expand the availability of essential life-saving services for pregnant women.

A randomized double blind placebo-controlled clinical trial of Hochuekkito, a traditional herbal medicine, in the treatment of elderly patients with weakness N of one and responder restricted design.

OBJECTIVE: To evaluate the effects of Hochuekkito, a traditional Japanese and Chinese medicine, in the treatment of elderly patients with general weakness. To devise a suitable study design for assessing the clinical effectiveness of traditional herbal medicines. METHODS: Fifteen elderly patients (mean +/- SD: age 78.4 +/- 7.8; m/f 3/12) participated in this study. A multicenter, prospective, randomized, double-blind, placebo-controlled study with N of one and responder restricted design was performed. After the run-in period, the patients were divided into responders and non-responders. Only responders were entered in the study, and were randomized into three groups: an active-placebo group, a placebo-active group and an active-active group. The study consisted of two 6-week terms with a 2-week washout period in between. We assessed the Short Form 36 Health Survey (SF-36) and Profile of Mood States (POMS) as an endpoint of quality of life (QOL). In addition, we assessed the biodefense status by measuring the natural killer cytolytic activity (NK activity), IL-2 producing activity of peripheral lymphocytes, lymphocyte proliferating activity and lymphocyte cell-surface antigens. RESULTS: The physical component summary of the SF-36 analysis significantly improved in the Hochuekkito-treated group. Four components (A-H: anger-hostility, F: fatigue, T-A: tension-anxiety, C: confusion) out of six improved in the Hochuekkito-treated group in the POMS analysis. Lymphocyte proliferating activity improved in the Hochuekkito-treated group but not significantly. Concerning the surface antigens of peripheral lymphocytes, the population of CD3 positive cells and CD3CD4 double positive cells increased in the Hochuekkito-treated group. CONCLUSION: We revealed that Hochuekkito improved the QOL and immunological status of elderly patients with weakness by randomized controlled trial. Our study design might be useful for assessing the efficacy of traditional herbal medicine in the future.

The effect of Juzen-taiho-to/TJ-48 on the expression of killer-cell immunoglobulin-like receptors (CD158a/b) on peripheral lymphocytes in vitro experiment.

Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been used traditionally to treat patients with anemia, anorexia or fatigue. It is well known that the treatment of TJ-48 result in the decrease of patient's complaints, as well as the increase of NK cytolytic activity (NK activity) although its augmentation is not clear in the other kampo formula from the clinical viewpoint. To investigate its biological activities, such as the augmentation of NK activity, we analyzed the effects of TJ-48 on the expression of killer-cell immunoglobulin-like receptors (KIRs) in vitro experiment. The peripheral lymphocytes were incubated in medium alone, or medium containing TJ-48 or interleukin-2 (IL-2) plus TJ-48 at several concentrations for 48 h. After each incubation, cells were collected and their KIRs were detected by flow cytometry using monoclonal antibodies CD158a and CD158b. TJ-48 increased the populations of CD16+CD158a+ and CD16+CD158b+ cells in a dose-dependent manner. In contrast, CD16-CD158a/b+ cells did not increase. Additionally, the extract of TJ-48 enhanced the increase of KIRs expression induced by IL-2. These actions contribute to the augmentation of NK cytolytic activity by TJ-48, and might explain, in part, its antitumor effects which has been observed in vivo.

The effects of a herbal medicine (Mao-to) in patients with chronic hepatitis C after injection of IFN-beta.

We found that a herbal medicine (Mao-to) relieves the side effects of interferon (IFN)-beta and the combination therapy improves the biochemical response rate. However, the exact mechanism by which Mao-to is effective remains to be established. We conducted a controlled trial to clarify the effects of Mao-to. The study was carried out in 18 patients with chronic hepatitis C, and we examined subjective symptoms, body temperature and cytokines such as interleukin (IL)-beta, IL-1receptor antagonist (ra), IL-6 and TNF-alpha. Each patient received 6 million units of IFN-beta intravenously. Mao-to was given orally just before, just after, and 1 hour after IFN administration. The control study was carried out 6 months after the combination therapy of Mao-to and IFN-beta. The scores for general malaise, arthralgia and discomfort were significantly lower in the combination group than in control group. Body temperature did not significantly differ between the two groups. Plasma IL-6 level and IL-1ra were significantly elevated in the combination group compared to control (P = 0.0057 and 0.0003, respectively). Mao-to did not affect plasma concentrations of IL-1beta and TNF-alpha. We considered the increment of IL-1ra caused by Mao-to is to be one of the key factors involved in reducing the flu-like symptoms accompanying IFN-beta and improving the biochemical response rate.

A comparative study between excess-dose users and regular-dose users of rhubarb contained in Kampo medicines.

With prolonged use of rhubarb-containing Kampo medicines, some patients come to ask for high-dose rhubarb because of deteriorated reactivity to rhubarb. We divided patients into two groups in terms of rhubarb-dose, and compared clinical backgrounds between regular-dose group and excess-dose group. Patients who were treated with rhubarb-containing Kampo extracts (manufactured prescriptions) or Kampo formulae (decoctions) for more than 12 months were enrolled. These two groups were compared for age, sex, shape of stool, abdominal symptoms, existence of hemorrhoids, Kampo diagnosis of abdomen, past stimulant laxative use, duration of stimulant laxative use before the first administration of rhubarb, duration of rhubarb use in our hospital, and initial existence of stimulant pain caused by taking stimulant laxatives for the first time. No significant difference was shown between the two groups in terms of age, duration of stimulant laxative-use before the first prescription of rhubarb, shape of stool, abdominal symptoms, existence of hemorrhoids, or duration of rhubarb-use. However, most patients in the regular-dose group had initial stimulant pain of the abdomen upon taking stimulant laxatives for the first time, but most patients in the excess-dose group did not (p < 0.001). All patients except one in the regular dose group had the sign of "umbilical region tenderness on pressure", but half of the excess-dose group did not have it (p = 0.041). Based on these findings, the absence of "initial stimulant pain" and the absence of "umbilical region tenderness on pressure" may predict increasing or excess use of rhubarb, and long-term use of rhubarb should be discouraged more strongly in the patients without these signs.

Incidence and clinical features of liver injury related to Kampo (Japanese herbal) medicine in 2,496 cases between 1979 and 1999: problems of the lymphocyte transformation test as a diagnostic method.

We retrospectively examined the summaries of all admission records of patients from 1979 to 1999 in our department, and selected for further study all liver injuries suspected of being related to Kampo medicines. Among 2,496 summaries, 30 summaries described liver disorders suspected of being related to Kampo medicines. Whether there was a causal relationship between the use of Kampo medication and the occurrence of liver injury was assessed according to the criteria described by Haller and Benowitz (2000), independently of the results of the lymphocyte transformation test (LTT). Among 30 events, we concluded that 9 were definitely unrelated, and 6 were probably unrelated to the use of Kampo medicines. Nine events (0.36% of 2,496 patient admissions and 0.06% of 14,616 outpatients) were considered possibly related, and only 6 events (0.24% of 2,496 patient admissions and 0.04% of 14,616 outpatients) were judged to be definitely or probably related to Kampo medicines. Low-grade eosinophilia was observed in a few patients of these "related" groups, and no fever or rash was observed in these "related" groups. Other clinical features, including type of liver injury, duration of Kampo medicine-use, recovery period and laboratory data, were not different from liver injuries associated with western drugs. Most patients in the definitely "unrelated" group were positive in the LTT for the suspect Kampo medicine, suggesting that the LTT may be unreliable for the diagnosis of Kampo-medicine-induced liver injury. From 1979 to 1999, our use of Kampo medicines to treat patients resulted in a low rate of liver injury and no fatalities.

Isolation of a MADS-box gene (ERAF17) and correlation of its expression with the induction of formation of female flowers by ethylene in cucumber plants (Cucumis sativus L.).

Ethylene regulates sex expression in cucumber (Cucumis sativus L.) plants. When the apices of monoecious cucumber seedlings (cv. Shimoshirazu-jibai) were treated with the ethylene-releasing compound, ethephon, female flowers were induced at the nodes. To clarify the action of ethylene in the regulation of sex expression, we attempted to isolate genes whose expression changed during induction of the formation of female flowers at the apices of these cucumber plants upon treatment with ethephon. Using the differential-display method, we identified 20 clones (#1 to #20) that reflected differences in the accumulation of transcripts in apices treated or not treated with ethephon. Sequence analysis of cDNA fragments revealed that the cDNA #17 had the sequence of a MADS-box gene. We isolated the full-length cDNA and showed that it included both a MADS box and a K box, and the corresponding gene was designated ERAF17. We examined the expression of ERAF17 in the apices of cv. Shimoshirazu-jibai and in those of a gynoecious cultivar (Rensei). In these cultivars, the timing and levels of expression of the ERAF17 transcript were correlated with the development of female flowers. Induction of the synthesis of the ERAF17 transcript by ethephon occurred within 4 h of the start of treatment and continued for 4 days at least. Expression of ERAF17 at apices was localized in the floral buds of the gynoecious cultivar, and expression was maintained in female flowers thorough their development. Our results suggest that the induction of the formation of female flowers by ethylene might be regulated by the expression of ERAF17 in floral buds at the apices of cucumber plants and that expression of this gene might also be involved in the development of female flowers.

Gastric proteinase digestion of caseins in newborn pups of the mouse.

Casein micelles of mouse milk consist of alpha-, beta-, gamma-, and kappa-caseins. By digestion with alkaline phosphatase, they were separated as an independent band by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). The compositions of alpha-, beta-, gamma-, and kappa-caseins were 24.3, 25.1, 9.4, and 41.2% in colostrum, and 36.8, 15.6, 11.9, and 35.7% in mature milk, respectively. Zero-day-old pups were allowed to access either colostrum or mature milk, and the aggregated milk in the stomach was analyzed by SDS-PAGE. Caseins in colostrum were digested more rapidly and efficiently than those in mature milk. Among the seven peptides present in the aggregated caseins, four peptides were colostrum-specific and derived from alpha- and gamma-caseins. It was expected that colostrum-specific and soluble peptides were generated from alpha- and gamma-caseins through gastric proteinase digestion. Amino acid sequence analysis and the pH of the aggregated milk suggested that caseins in the stomach were digested by a chymotrypsin-like proteinase. Caseins in colostrum were different from those in mature milk, with respects to the casein composition as well as the gastric proteinase sensitivity. It is concluded that the lactating mice on the day of parturition supply particular caseins to their young.

Administration of isoferulic acid improved the survival rate of lethal influenza virus pneumonia in mice.

BACKGROUND: Isoferulic acid (IFA) is a main active ingredient of the rhizoma of Cimicifuga beracleifolia, which is used frequently in Japanese traditional medicine as an anti-inflammatory drug. It has been revealed that IFA inhibits the production of macrophage inflammatory protein-2 (MIP-2), which is a murine counterpart of the chemokine family that may contribute to the pathogenesis of inflammatory diseases through the chemotactic activity for inflammatory and immune effector cells. AIM OF THE STUDY: In this study, we investigated the therapeutic effect of IFA on the progression of lethal influenza virus pneumonia in mice by comparison with that of dexamethasone (DX), a potent inhibitor for various inflammatory cytokines including MIP-2. METHODS: Mice were infected by intranasal inoculation of influenza virus under ether anesthesia. The IFA or DX was given by oral administration once daily for 4 days after infection. After infection, the survival rate and the change in body weight were daily monitored. RESULTS: IFA administration markedly improved the survival rate and body weight loss of influenza virus-infected mice in a suitable dose range (0.5 mg/day). However, DX administration did not show a beneficial effect at any dose. CONCLUSION: These data suggested that IFA is a novel tool not only for the intervention therapy, but also for the studies on the pathogenesis of influenza virus-induced pneumonia.

Is use of exogenous estrogen associated with temporomandibular signs and symptoms?

BACKGROUND: Studies of historical data suggest a link between exogenous estrogen use and referral for treatment for temporomandibular disorders, or TMDs. The purpose of the authors' study was to determine the association between exogenous estrogen use and signs and symptoms of TMD assessed by direct physical examination in a randomly selected community sample of primarily postmenopausal women. METHODS: A calibrated clinical examiner examined a stratified random sample of 510 women aged 37 to 82 years using the Craniomandibular Index, or CMI. All medications that subjects were taking at the time of the examination were identified by interview and examination of subjects' medication containers on two occasions. One hundred seventy-four subjects were taking medications containing estrogen, and 336 were taking no such medications. RESULTS: The muscle and joint signs and symptoms of women taking and not taking estrogen were not significantly different after the authors controlled for sociocultural, demographic and health care utilization variables. Estrogen use also failed to distinguish women receiving relatively high and low scores on the CMI. CONCLUSION: Estrogen replacement therapy does not place women at increased risk of developing TMDs. CLINICAL IMPLICATIONS: Clinicians need not be concerned that patients taking oral contraceptives or replacement estrogens are at increased risk of developing TMDs.

[Chemical studies on the analgesic indole alkaloids from the traditional medicine (Mitragyna speciosa) used for opium substitute].

The leaves of a tropical plant, Mitragyna speciosa Korth. (Rubiaceae), have been traditionally used as a substitute for opium. By phytochemical studies on the constituents of the plant growing in Thailand as well as in Malaysia, several 9-methoxy-Corynanthe-type monoterpenoid indole alkaloids including new natural products were isolated. The structures of these new compounds were elucidated by the modern spectroscopic methods and/or chiral-total syntheses. The chiral total synthesis of (-)-mitragynine, a major component of this plant, was achieved. Potent opioid agonistic properties of mitragynine, which acts on mu- and delta-opioid subtype receptors, and of mitragynine pseudoindoxyl, whose analgesic activity is more potent than that of morphine, were clarified in in vitro experiments. The essential structural features in mitragynine for revealing the analgesic activity were elucidated by pharmacological evaluation of the natural and synthetic mitragynine derivatives.

Shosaiko-to and other Kampo (Japanese herbal) medicines: a review of their immunomodulatory activities.

The use of alternative medicine, including consumption of herbal products and dietary supplements, has been increasing substantially both in the United States and in Western Europe. One area that is garnering increased attention is the use of Oriental Medicine including Kampo, or Japanese herbal medicine. Herein, we review representative examples of research available on the most common use of Kampo medicinals, namely to improve the immune response. We also provide an extensive background on the history of Kampo. There are more than 210 different Kampo formulae used in Japan and most uses of Kampo are to modulate the immune response, i.e. to improve immunity. We have extracted data on seven common Kampo medicinals, and the data are reviewed with respect to in vitro and in vivo activities for both humans and experimental animals; the ingredients as well as the problems with classification of these materials are presented. Research suggests that Kampo herbals are biologically active and may have therapeutic potential. While it is believed that Kampo medicines have few side effects, there is a paucity of data on their toxicity as well as a relative lack of knowledge of the bioactive constituents and potential drug interactions of these agents.

[Analysis of the contractions evoked by sympathetic nerve stimulation, and thermal effect on the guinea-pig vas deferens--study as a model for the thermotherapy of benign prostatic hyperplasia].

BACKGROUND: The present study was designed to investigate the mechanism of thermotherapy on benign prostatic hyperplasia (BPH), using the guinea-pig vas deferens as a model for BPH. The components of contractions elicited by electrical field stimulation and nicotine were analyzed, and the thermal effect on the vas deferens was examined. METHODS: The vas deferens was dissected, suspended vertically through two silver ring electrodes, and attached to an isometric transducer. The electrical stimulation of 10 constant current pulses (10 mA) with 0.3 msec in duration of 5, 10, and 40 Hz was achieved under air-gap condition. Drugs were added directly to a 5 ml Magnus tube containing Tyrode solution (36 degrees C) gassed with a 95% O2-5% CO2 mixture. The components of contractions evoked by electrical stimulation and nicotine were investigated by tetrodotoxin (TTX), and blocking agents of alpha 1-adrenoceptors and/or purinoceptors. Thermal effect on electrically evoked contractions was examined at incubation temperature of 25 degrees C (control), 43 degrees C, 45 degrees C, 46 degrees C and 47 degrees C for 1 hour. RESULTS: Nicotine (200 microM) elicited biphasic contractions, which were triggered by corelease of noradrenaline (NA) and ATP (N-ATP) from sympathetic nerve terminals by activation of prejunctional nicotine receptors. NA and N-ATP caused the corresponding contractions, alpha 1 and N-ATP components, respectively. Combined application of prazosin (1 microM) and suramin (50 microM) abolished these contractions. Activation of post-junctional alpha 1-adrenoceptors by NA caused release of ATP from muscle cells to produce the contraction (alpha 1-ATP component), which was sensitive to both suramin and prazosin. N-ATP and alpha 1 components attributed to fast and slow part of the contraction, respectively. Electrical field stimulation caused biphasic contractions which consisted of both neurogenic (TTX-sensitive) and non-neurogenic (TTX-insensitive) components. An increase in stimulation frequency (5 to 40 Hz) increased the neurogenic components, which contained alpha 1 and N-ATP components, as well as the case of nicotine. The non-neurogenic components consisted of alpha 1-ATP, muscle-derived ATP (m-ATP) and unknown substance 'X' components. Nifedipine (10 microM). L-type Ca2+ channel blocker, markedly reduced the contractions induced by bath applied phenylephrine (alpha 1-agonist, 100 microM) but only partially blocked the contractions produced by bath applied ATP (500 microM). The contractile force in amplitude and neurogenic components induced by electrical field stimulation did not change at 43 degrees C, but both declined significantly above 45 degrees C. The neurogenic components at 45 degrees C and 46 degrees C were suppressed to 22 +/- 6% and 14 +/- 3% (mean +/- SD) of control, respectively. All the contractile responses were abolished at 47 degrees C. CONCLUSION: The contractions of the guinea-pig vas deferens evoked by electrical field stimulation consisted of alpha 1, N-ATP, alpha 1-ATP, m-ATP and X components. Sympathetic nerve fibers in the muscles were completely inactivated by thermal exposure at 47 degrees C for 1 hour. The results suggest that the minimal temperature for thermotherapy of BPH should be 47 degrees C.

Pallidal and cerebellar afferents to pre-supplementary motor area thalamocortical neurons in the owl monkey: a multiple labeling study.

In the present study, we determined where thalamic neurons projecting to the pre-supplementary motor area (pre-SMA) are located relative to pallidothalamic and cerebellothalamic inputs and nuclear boundaries. We employed a triple-labeling technique in the same owl monkey (Aotus trivirgatus). The cerebellothalamic projections were labeled with injections of wheat germ agglutinin conjugated to horseradish peroxidase, and the pallidothalamic projections were labeled with biotinylated dextran amine. The pre-SMA was identified by location and movement patterns evoked by intracortical microstimulation and injected with the retrograde tracer cholera toxin subunit B. Brain sections were processed sequentially using different chromogens to visualize all three tracers in the same section. Alternate sections were processed for Nissl cytoarchitecture or acetylcholinesterase chemoarchitecture for nuclear boundaries. The cerebellar nuclei primarily projected to posterior (VLp), medial (VLx), and dorsal (VLd) divisions of the ventral lateral nucleus; the pallidum largely projected to the anterior division (VLa) of the ventral lateral nucleus and the parvocellular part of the ventral anterior nucleus (VApc). However, we also found zones of overlapping projections, as well as interdigitating foci of pallidal and cerebellar label, particularly in border regions of the VLa and VApc. Thalamic neurons labeled by pre-SMA injections occupied a wide band and were especially concentrated in the VLx and VApc, cerebellar and pallidal territories, respectively. Labeled thalamocortical neurons overlapped cerebellar inputs in the VLd and VApc and overlapped pallidal inputs in the VLa and the ventral medial nucleus. The results demonstrate that inputs from both the cerebellum and globus pallidus are relayed to the pre-SMA.

Improvement of myocardial fatty acid metabolism through L-carnitine administration to chronic hemodialysis patients.

The concentration of carnitine, which is essential to fatty acid metabolism, can decrease markedly in patients on long-term hemodialysis coincident with life-threatening cardiac damage. However, administration of L-carnitine improves the myocardial function of these patients. To evaluate the underlying events of this phenomenon, we used recently developed technology, (123)I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) myocardial scintigraphy, as a test of myocardial fatty acid metabolism. Our results showed that the free carnitine concentration (19.2 +/- 6.5 micromol/l) was lower in 11 chronically dialyzed patients than in 8 healthy controls (49.3 +/- 7.7 micromol/l, p < 0. 0001). Additionally the heart to mediastinal ratio (H/M) of BMIPP was higher for these patients than for the controls (1.91 +/- 0.19 vs. 1.52 +/- 0.24, p < 0.005), and the patients' washout rate (WOR) of BMIPP was lower (17.2 +/- 6.0 vs. 22.8 +/- 4.2%, p < 0.05). After L-carnitine was administered orally to the patients at doses of 1 g/day for 1 month and 0.5 g/day for the following month, the concentration of free carnitine in their sera increased to 85.4 +/- 27.0 micromol/l (p < 0.0001). Although the H/M ratio did not change (1.89 +/- 0.20) with this treatment, their WOR increased to 21.9 +/- 6.6% (p < 0.001), similar to that of controls. The left ventricular end-diastolic dimension and left ventricular fractional shortening remained unchanged, as shown by echocardiography. The results presented here denote that a carnitine deficiency in chronically hemodialyzed patients disrupts their myocardial fatty acid metabolism, which is improved by L-carnitine supplementation.

Opioid receptor agonistic characteristics of mitragynine pseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant Mitragyna speciosa.

We have previously elucidated the opiate-like action of mitragynine, an active principle isolated from the Thai medicinal plant Mitragyna speciosa. In the present study, effects of the related compound, mitragynine pseudoindoxyl on electrically stimulated contraction in guinea pig ileum and mouse vas deferens, and on its binding affinity in the guinea pig brain membranes were studied. Mitragynine pseudoindoxyl inhibited the electrically stimulated ileum and mouse vas deferens contractions in a concentration-dependent manner. In the ileum, the effective concentration is in an nM order, being nearly equivalent to reported concentrations of the micro-opioid receptor agonist [D-Ala2, Met-Phe4, Gly-ol5] enkephalin (DAMGO), and is 100- and 20-fold smaller than those of mitragynine and morphine, respectively. In the vas deferens, it is 35-fold smaller than that of morphine. The inhibitory action of mitragynine pseudoindoxyl in the ileum was antagonized by the non-selective opioid receptor antagonist naloxone and the micro-receptor antagonist naloxonazine. It was also antagonized by the delta-receptor antagonist naltrindole in the vas deferens. Mitragynine pseudoindoxyl showed a similar binding affinity to DAMGO and naltrindole at micro- and delta-receptors, respectively. However, the affinity at kappa-receptors was negligible. The present study demonstrates that mitragynine pseudoindoxyl, a novel alkaloid structurally different from other opioid agonists, acts on opioid receptors, leading to a potent inhibition of electrically stimulated contraction in the ileum through the micro-receptors and in mouse vas deferens through delta-receptors.