The sleep-enhancing effect of valerian inhalation and sleep-shortening effect of lemon inhalation

We examined the effects of odorant inhalation on the sleep-wake states in rats. Odorants used in the experiment were clove, jasmine, lavender, lemon, peppermint, pine, rose, sandalwood, valerian, and ylang-ylang. Valerian and rose inhalation significantly prolonged the pentobarbital-induced sleeping time, whereas lemon inhalation significantly shortened it. The effect of valerian inhalation was markedly noticeable. In the anosmic rats, a significant effect of odorants on the pentobarbital sleep time was not seen. Electroencephalographic studies on natural sleep revealed that rose inhalation did not exert any significant effect on sleep, but a significant shortening in sleep latency and a significant prolonging in total sleep time were observed with valerian inhalation, whereas a significant prolonging in sleep latency was observed with lemon inhalation. Such effects of valerian and lemon inhalation were not admitted in anosmic rats. gamma-Aminobutyric acid (GABA) transaminase assay indicates that valerian inhalation decreases the activity of the enzyme and enhances GABA activity. Although valerian has been reported to exert a good effect for sleep as a medicine for internal use, the present study is the first medical report suggesting that the inhalation of valerian may enhance the sleep. On the other hand, the present results may suggest the possibility that lemon inhalation may cause a worsening of insomnia symptoms.     

The effects of mannitol and salinity stresses on growth and biochemical accumulations in lemon balm

The effects of saline irrigation water and mannitol on the growth and content of essential oil, photosynthetic pigments, soluble sugars, proline, Na, macroelements (N–P–K) and microelements (Mg–Zn–Fe–Mn) of lemon balm (Melissa officinalis L.) plants were investigated. Saline irrigation water decreased certain growth characters (total leaf area, leaf number, and total fresh and dry mass). The photosynthetic pigments (chlorophylls a and b, total carotenoids) and mineral content (N–P–K–Mg–Zn–Fe–Mn) also decreased as saline irrigation water level increased. Saline irrigation water promoted the accumulation of essential oil content and its main components (citronellal, citronellol and geranyl acetate) as well as total soluble sugars, proline and Na⁺ contents. The plants treated with saline irrigation water × mannitol resulted in higher plant growth, essential oil, total soluble sugars, proline, macro and micronutrient values than those treated with saline irrigation water alone, photosynthetic pigments and Na demonstrated an opposite trend.     

The effects of mannitol and salinity stresses on growth and biochemical accumulations in lemon balm

The effects of saline irrigation water and mannitol on the growth and content of essential oil, photosynthetic pigments, soluble sugars, proline, Na, macroelements (N–P–K) and microelements (Mg–Zn–Fe–Mn) of lemon balm (Melissa officinalis L.) plants were investigated. Saline irrigation water decreased certain growth characters (total leaf area, leaf number, and total fresh and dry mass). The photosynthetic pigments (chlorophylls a and b, total carotenoids) and mineral content (N–P–K–Mg–Zn–Fe–Mn) also decreased as saline irrigation water level increased. Saline irrigation water promoted the accumulation of essential oil content and its main components (citronellal, citronellol and geranyl acetate) as well as total soluble sugars, proline and Na⁺ contents. The plants treated with saline irrigation water × mannitol resulted in higher plant growth, essential oil, total soluble sugars, proline, macro and micronutrient values than those treated with saline irrigation water alone, photosynthetic pigments and Na demonstrated an opposite trend.     

Effects of lemon balm (Melissa officinalis L.) extract on germination and seedling growth of six plants

The n-hexane-, acetone- and water-soluble fractions obtained from an aqueous acetone extract of lemon balm (Melissa officinalis L.) shoots inhibited the germination and the growth of roots and shoots of cockscomb (Amaranthus caudatus L.), cress (Lepidium sativum L.), crabgrass (Digitaria sanguinalis L.), timothy (Phleum pratense L.), lettuce (Lactuca sativa L.) and ryegrass (Lolium multiflorum Lam.). The inhibitory activity of the water-soluble fraction was the greatest, followed by that of acetone- and n-hexane-soluble fractions in all bioassays. The effectiveness of these fractions on the roots was greater than that of the shoots of the test plants. Significant reductions in the germination and growth of the roots and shoots were observed as the extract concentration increased. Such rate-dependent responses of the test plants to the fractions suggest that each fraction might contain allelochemical(s), but that the greatest potential was in the water-soluble fraction.     

Interactions of valerian extracts and a fixed valerian-hop extract combination with adenosine receptors

Phytopharmaceuticals and dietary supplements containing valerian are used as mild sleep-inducing agents. An in vitro radioligand binding assay at A(1) and A(2A) adenosine receptors (ARs) was conducted with a fixed extract combination of valerian and hop (Ze 91019) to investigate a possible mechanism for the pharmacological activity of the extract. Component extracts of valerian and hop were also individually investigated. The fixed combination Ze 91019 as well as the valerian extracts therein exhibited selective affinity to A(1)ARs (K(i) = 0.15-0.37 mg/mL vs [(3)H]CCPA). The same extracts exhibited partial agonist activity at the A(1) adenosine receptor as indicated by a lower degree of stimulation of [35S]GTP gamma S binding in membrane preparations of CHO-hA(1) cells as compared to the full A(1) AR agonist N(6)-cyclopentyladenosine (CPA). In addition valerian extract inhibited cAMP accumulation in CHO-hA(1) cell membranes. The partial agonistic activity at A(1)ARs may thus play a role in the sleep inducing effect of Ze 91019 and the valerian extract therein.     

A phase I clinical study of Andrographis paniculata fixed combination Kan Jang versus ginseng and valerian on the semen quality of healthy male subjects.

The safety of different doses of Kan Jang--a fixed combination of Andrographis paniculata special extract (SHA-10) and Acanthopanax senticosus--compared to two extensively used medicinal plants, Valeriana officinalis and Panax ginseng in the form of standardized extracts, has been examined. A phase I clinical study was designed to evaluate the effect on semen quality of healthy males in terms of spermatogenesis and quality of semen. The results of the study revealed no significant negative effect of Kan Jang on male semen quality and fertility, but rather a positive trend with respect to the number of spermatozoids in the whole ejaculate, the percentage of active (normokinetic) forms of spermatozoids, and fertility indexes, together with a decrease in the percentage of inactive (diskinetic) forms of spermatozoids. In the group receiving ginseng, no significant negative effects on the fertility parameters were revealed and there was a clear decrease in the percentage of diskinetic forms of spermatozoids. Subjects receiving valerian showed a temporary increase in the percentage of normokinetic spermatozoids and a decrease in diskinetic forms, but these changes had no effect on fertility indices. The results indicate that Kan Jang, ginseng and valerian are safe with respect to effects on human male sterility when administered at dose levels corresponding to approximately 3 times the human daily dose.     

Extracts from peppermint leaves,lemon balm leaves and in particular angelica roots mimic the pro-secretory action of the herbal preparation STW 5 in the human intestine

AimThe herbal preparation STW 5 contains fresh plant extracts from bitter candytuft whole plant, extracts from greater celandine herb, angelica root, lemon balm leaves, peppermint leaves, caraway fruit, liquorice root, chamomile flower and milk thistle fruit. We recently reported that STW 5 increased intestinal chloride secretion and proposed that this action may be involved in its clinical efficacy in the treatment of irritable bowel syndrome. The aim of this study was to identify the extracts responsible for the secretory action in order to provide the basis to develop novel target oriented herbal combinations.MethodsWe used the Ussing chamber voltage clamp technique to study the effects of individual extracts of STW 5 on short circuit current (Isc, reflecting electrogenic ion transport across epithelial cells) in mucosal/submucosal preparations of human small or large intestinal specimens and the human epithelial cell line T84.ResultsSTW 5 at concentrations of 512 µg/ml and 5120 µg/ml evoked an increase in Isc. The increase at the lower concentration was due to pro-secretory effects of angelica which were nerve mediated. The increase at the higher concentration was additionally mimicked by peppermint and lemon balm. The remaining extracts did not influence I_SC in the large intestine. The results were similar in T84 cells except that angelica had no effect while chamomile induced secretion. These pro-secretory effects were reduced by adenylate cyclase inhibitor MDL-12330A, cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTR_inh-172 and calcium activated chloride channels blocker 4-acetamido-4-isothiocyanatostilbene-2,2-disulphonic acid (SITS). Liquorice decreased I_SC only in small intestine which was reversed by the epithelial sodium channel blocker amiloride.ConclusionsResults suggested that the pro-secretory action of STW 5 is mainly due to angelica with lesser contribution of peppermint and lemon balm. Their effects involve activation of cAMP- and Ca⁺⁺-activated Cl⁻ channels. We suggest that peppermint, lemon balm and in particular angelica may be the basis to develop novel herbal preparations to specifically treat secretory disorder based on impaired epithelial secretion, such as constipation.     

Potent pro-apoptotic combination therapy is highly effective in a broad range of cancers

Primary or acquired therapy resistance is a major obstacle to the effective treatment of cancer. Resistance to apoptosis has long been thought to contribute to therapy resistance. We show here that recombinant TRAIL and CDK9 inhibition cooperate in killing cells derived from a broad range of cancers, importantly without inducing detectable adverse events. Remarkably, the combination of TRAIL with CDK9 inhibition was also highly effective on cancers resistant to both, standard-of-care chemotherapy and various targeted therapeutic approaches. Dynamic BH3 profiling revealed that, mechanistically, combining TRAIL with CDK9 inhibition induced a drastic increase in the mitochondrial priming of cancer cells. Intriguingly, this increase occurred irrespective of whether the cancer cells were sensitive or resistant to chemo- or targeted therapy. We conclude that this pro-apoptotic combination therapy has the potential to serve as a highly effective new treatment option for a variety of different cancers. Notably, this includes cancers that are resistant to currently available treatment modalities.Subject terms: Cancer models, Cell biology, Preclinical research     

A clinical model of obesity treatment is more effective in preschoolers and Spanish speaking families

Objective:

Preschool and minority children have not been well represented in obesity treatment studies. This analysis of clinical obesity treatment was carried out within a diverse population of children 2‐12 years to identify demographic characteristics associated with successful treatment.

Design and Methods:

A medical record review captured BMI and demographics for children 2‐12 years who began treatment during a 42‐month period (n = 479). Associations of body mass index z‐score (BMI‐Z) change with child and family demographics were examined with logistic regression and time‐to‐event analysis.

Results:

Treatment led to a mean BMI‐Z decrease of 0.18. Half of children with follow‐up (n = 273) exceeded the a priori cut‐off for successful treatment of ?0.1 BMI‐Z. Preschoolers and children of Spanish‐speakers were more likely to succeed, (Adjusted OR: 5.8 [95% CI: 2.7‐12.2] and 2.3 [95% CI: 1.1, 4.9]). The hazard ratio for treatment failure was 3.7 [95% CI: 2.1, 6.8] for children starting treatment at 6‐12 years compared to preschoolers, adjusted for other demographics.

Conclusions:

This mode of treatment was more likely to succeed among children treated before school age and among children whose parents spoke only Spanish. Screening and treatment for obesity in preschoolers and Hispanic immigrant families deserve further prospective study.

     

Tamoxifen is effective in the treatment of Leishmania amazonensis infections in mice

Background

Chemotherapy is still a critical issue in the management of leishmaniasis. Until recently, pentavalent antimonials, amphotericin B or pentamidine compounded the classical arsenal of treatment. All these drugs are toxic and have to be administered by the parenteral route. Tamoxifen has been used as an antiestrogen in the treatment and prevention of breast cancer for many years. Its safety and pharmacological profiles are well established in humans. We have shown that tamoxifen is active as an antileishmanial compound in vitro, and in this paper we analyzed the efficacy of tamoxifen for the treatment of mice infected with Leishmania amazonensis, an etiological agent of localized cutaneous leishmaniasis and the main cause of diffuse cutaneous leishmaniasis in South America.

Methodology/Principal Findings

BALB/c mice were infected with L. amazonensis promastigotes. Five weeks post-infection, treatment with 15 daily intraperitoneal injections of 20 mg/kg tamoxifen was administered. Lesion and ulcer sizes were recorded and parasite burden quantified by limiting dilution. A significant decrease in lesion size and ulcer development was noted in mice treated with tamoxifen as compared to control untreated animals. Parasite burden in the inoculation site at the end of treatment was reduced from 10^8.5±0.7 in control untreated animals to 10^5.0±0.0 in tamoxifen-treated mice. Parasite load was also reduced in the draining lymph nodes. The reduction in parasite number was sustained: 6 weeks after the end of treatment, 10^15.5±0.5 parasites were quantified from untreated animals, as opposed to 10^5.1±0.1 parasites detected in treated mice.

Conclusions/Significance

Treatment of BALB/c mice infected with L. amazonensis for 15 days with tamoxifen resulted in significant decrease in lesion size and parasite burden. BALB/c mice infected with L. amazonensis represents a model of extreme susceptibility, and the striking and sustained reduction in the number of parasites in treated animals supports the proposal of further testing of this drug in other models of leishmaniasis.     

A specific combination of substrates is involved in signal transduction by the kit-encoded receptor.

The kit protooncogene encodes a transmembrane tyrosine kinase related to the receptors for the platelet derived growth factor (PDGF-R) and the macrophage growth factor (CSF1-R), and was very recently shown to bind a stem cell factor. To compare signal transduction by the kit kinase with signaling by homologous receptors we constructed a chimeric protein composed of the extracellular domain of the epidermal growth factor receptor (EGF-R) and the transmembrane and cytoplasmic domains of kit. We have previously shown that the chimeric receptor transmits potent mitogenic and transforming signals in response to the heterologous ligand. Here we demonstrate that upon ligand binding, the ligand-receptor complex undergoes endocytosis and degradation and induces short- and long-term cellular effects. Examination of the signal transduction pathway revealed that the activated kit kinase strongly associates with phosphatidylinositol 3'-kinase activity and a phosphoprotein of 85 kd. In addition, the ligand-stimulated kit kinase is coupled to modifications of phospholipase C gamma and the Raf1 protein kinase. However, it does not lead to a significant change in the production of inositol phosphate. Comparison of our results with the known signaling pathways of PDGF-R and CSF1-R suggests that each receptor is coupled to a specific combination of signal transducers.     

Zoledronic acid is effective in the management of migratory osteoporosis unresponsive to conservative treatment and risedronate: A case report

We describe a case of a 55-year-old woman with migratory osteoporosis (MO) which initially presented as pain with bone marrow edema (BME) evident in magnetic resonance imaging (MRI) of the left ankle and was managed with non-weight-bearing (NWB). The patient was already treated with per os risedronate for postmenopausal osteoporosis. After significant initial improvement, pain and BME relapsed in the left ankle and additionally expanded to insult the foot, while 3 months later the left hip was also affected. Since the combination of NWB, analgesics and risedronate had failed to control the disease, a single infusion of 5mg zoledronic acid (ZA) was administered. One month later the pain in all affected sites was disappeared and BME resolved as shown by MRI performed 3.5 months following ZA infusion. The patient, eventually, returned to her daily routine. This case underlines the effectiveness of ZA in MO and the need for more aggressive treatment in this disease.