MaquiBright™ standardized maqui berry extract significantly increases tear fluid production and ameliorates dry eye-related symptoms in a clinical pilot trial.

AIM: Dry eye symptoms, resulting from insufficient tear fluid generation, represent a considerable burden for a largely underestimated number of people. We concluded from earlier pre-clinical investigations that the etiology of dry eyes encompasses oxidative stress burden to lachrymal glands and that antioxidant MaquiBright™ Aristotelia chilensis berry extract helps restore glandular activity. METHODS: In this pilot trial we investigated 13 healthy volunteers with moderately dry eyes using Schirmer test, as well as a questionnaire which allows for estimating the impact of dry eyes on daily routines. Study participants were assigned to one of two groups, receiving MaquiBright™ at daily dosage of either 30 mg (N.=7) or 60 mg (N.=6) over a period of 60 days. Both groups presented with significantly (P<0.05) improved tear fluid volume already after 30 days treatment. Schirmer test showed an increase from baseline 16.3±2.6 mm to 24.4±4.8 mm (P<0.05) with 30 mg MaquiBright™ and from 18.7±1.9 mm to 27.6±3.4 mm with 60 mg (P<0.05), respectively. Following treatment with 30 mg MaquiBright™ for further 30 days, tear fluid volume dropped slightly to 20.5±2.8 mm, whereas the improvement persisted with 60 mg treatment at 27.1±2.7 mm after 60 days treatment (P<0.05 vs. baseline). RESULTS: The burden of eye dryness on daily routines was evaluated employing the "Dry Eye-related Quality of life Score" (DEQS), with values spanning from zero (impact) to a maximum score of 60. Participants had comparable baseline values of 41.0±7.7 (30 mg) and 40.2±6.3 (60 mg). With 30 mg treatment the score significantly decreased to 21.8±3.9 and 18.9±3.9, after 30 and 60 days, respectively. With 60 mg treatment the DEQS significantly decreased to 26.9±5.3 and 11.1±2.7, after 30 and 60 days, respectively. Blood was drawn for safety analyses (complete blood rheology and -chemistry) at all three investigative time points without negative findings. CONCLUSION: In conclusion, while daily supplementation with 30 mg MaquiBright™ is effective, the dosage of 60 significantly increased tear fluid volume at all investigative time points and decreased dry eye symptoms to almost a quarter from initial values after two months treatment.

Enhancing phosphorus and zinc acquisition efficiency in rice: a critical review of root traits and their potential utility in rice breeding.

BACKGROUND: Rice is the world's most important cereal crop and phosphorus (P) and zinc (Zn) deficiency are major constraints to its production. Where fertilizer is applied to overcome these nutritional constraints it comes at substantial cost to farmers and the efficiency of fertilizer use is low. Breeding crops that are efficient at acquiring P and Zn from native soil reserves or fertilizer sources has been advocated as a cost-effective solution, but would benefit from knowledge of genes and mechanisms that confer enhanced uptake of these nutrients by roots. SCOPE: This review discusses root traits that have been linked to P and Zn uptake in rice, including traits that increase mobilization of P/Zn from soils, increase the volume of soil explored by roots or root surface area to recapture solubilized nutrients, enhance the rate of P/Zn uptake across the root membrane, and whole-plant traits that affect root growth and nutrient capture. In particular, this review focuses on the potential for these traits to be exploited through breeding programmes to produce nutrient-efficient crop cultivars. CONCLUSIONS: Few root traits have so far been used successfully in plant breeding for enhanced P and Zn uptake in rice or any other crop. Insufficient genotypic variation for traits or the failure to enhance nutrient uptake under realistic field conditions are likely reasons for the limited success. More emphasis is needed on field studies in mapping populations or association panels to identify those traits and underlying genes that are able to enhance nutrient acquisition beyond the level already present in most cultivars.

Antileishmanial activity of indole alkaloids from Aspidosperma ramiflorum.

The present study was designated to evaluate the antileishmanial activity of acid and basic fractions that were obtained after acid-basic extraction, from ethanolic 70% crude extract and pure compounds from the stem bark of Aspidosperma ramiflorum. The basic alkaloidal fraction presented a good activity against the extracellular form (promastigotes) of Leishmania (L.) amazonensis (LD(50) value<47 microg/ml). Based on these findings, the basic fraction was fractionated on silica gel column chromatography in a bioassay-guided fractionation affording individual purified ramiflorines A and B. Both ramiflorines A and B showed significant activity against Leishmania (L.) amazonensis (LD(50) values of 16.3+/-1.6 microg/ml and 4.9+/-0.9 microg/ml, respectively). Our results are promising, showing that these compounds are biologically active against Gram-positive bacteria.

Antibacterial activity of indole alkaloids from Aspidosperma ramiflorum

We evaluated the antibacterial activities of the crude methanol extract, fractions (I-V) obtained after acid-base extraction and pure compounds from the stem bark of Aspidosperma ramiflorum. The minimum inhibitory concentration (MIC) was determined by the microdilution technique in Mueller-Hinton broth. Inoculates were prepared in this medium from 24-h broth cultures of bacteria (10(7) CFU/mL). Microtiter plates were incubated at 37°C and the MICs were recorded after 24 h of incubation. Two susceptibility endpoints were recorded for each isolate. The crude methanol extract presented moderate activity against the Gram-positive bacteria B. subtilis (MIC = 250 µg/mL) and S. aureus (MIC = 500 µg/mL), and was inactive against the Gram-negative bacteria E. coli and P. aeruginosa (MIC > 1000 µg/mL). Fractions I and II were inactive against standard strains at concentrations of <=1000 µg/mL and fraction III displayed moderate antibacterial activity against B. subtilis (MIC = 500 µg/mL) and S. aureus (MIC = 250 µg/mL). Fraction IV showed high activity against B. subtilis and S. aureus (MIC = 15.6 µg/mL) and moderate activity against E. coli and P. aeruginosa (MIC = 250 µg/mL). Fraction V presented high activity against B. subtilis (MIC = 15.6 µg/mL) and S. aureus (MIC = 31.3 µg/mL) and was inactive against Gram-negative bacteria (MIC > 1000 µg/mL). Fractions III, IV and V were then submitted to bioassay-guided fractionation by silica gel column chromatography, yielding individual purified ramiflorines A and B. Both ramiflorines showed significant activity against S. aureus (MIC = 25 µg/mL) and E. faecalis (MIC = 50 µg/mL), with EC50 of 8 and 2.5 µg/mL for ramiflorines A and B, respectively, against S. aureus. These results are promising, showing that these compounds are biologically active against Gram-positive bacteria.

Antibacterial activity of indole alkaloids from Aspidosperma ramiflorum.

We evaluated the antibacterial activities of the crude methanol extract, fractions (I-V) obtained after acid-base extraction and pure compounds from the stem bark of Aspidosperma ramiflorum. The minimum inhibitory concentration (MIC) was determined by the microdilution technique in Mueller-Hinton broth. Inoculates were prepared in this medium from 24-h broth cultures of bacteria (10(7) CFU/mL). Microtiter plates were incubated at 37 masculineC and the MICs were recorded after 24 h of incubation. Two susceptibility endpoints were recorded for each isolate. The crude methanol extract presented moderate activity against the Gram-positive bacteria B. subtilis (MIC = 250 microg/mL) and S. aureus (MIC = 500 microg/mL), and was inactive against the Gram-negative bacteria E. coli and P. aeruginosa (MIC > 1000 microg/mL). Fractions I and II were inactive against standard strains at concentrations of < or =1000 microg/mL and fraction III displayed moderate antibacterial activity against B. subtilis (MIC = 500 microg/mL) and S. aureus (MIC = 250 microg/mL). Fraction IV showed high activity against B. subtilis and S. aureus (MIC = 15.6 microg/mL) and moderate activity against E. coli and P. aeruginosa (MIC = 250 microg/mL). Fraction V presented high activity against B. subtilis (MIC = 15.6 microg/mL) and S. aureus (MIC = 31.3 microg/mL) and was inactive against Gram-negative bacteria (MIC > 1000 microg/mL). Fractions III, IV and V were then submitted to bioassay-guided fractionation by silica gel column chromatography, yielding individual purified ramiflorines A and B. Both ramiflorines showed significant activity against S. aureus (MIC = 25 microg/mL) and E. faecalis (MIC = 50 microg/mL), with EC50 of 8 and 2.5 microg/mL for ramiflorines A and B, respectively, against S. aureus. These results are promising, showing that these compounds are biologically active against Gram-positive bacteria.

Roles and mechanisms of action of pituitary adenylate cyclase-activating polypeptide (PACAP) in growth hormone and prolactin secretion.

It appears that PACAP has a direct action on somatotrophs to release GH. The intracellular signal transduction mechanisms for PACAP might be similar to but partly distinct from those for GRH. PACAP might play a role in GH secretion induced by serotoninergic mechanisms but not in ultradian rhythm of GH secretion in the rat. PACAP can stimulate PRL release from the pituitary in rats possibly through indirect paracrine effect. In addition, PACAP might participate in regulation of PRL secretion via hypothalamic VIP.

Thonningianins A and B, new antioxidants from the African medicinal herb Thonningia sanguinea.

Two new ellagitannins, thonningianins A (1) and B (2), have been isolated from the African medicinal herb Thonningia sanguinea and their structures elucidated by interpretation of spectroscopic data. Both 1 and 2 showed strong free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) as shown by ESR analysis.

Increase production of lactonizing lipase (LipL) from Pseudomonas sp. strain 109 by lipids and detergents.

LipL of Pseudomonas sp. strain 109 is a unique lipase capable of catalyzing macrocyclic lactone synthesis using omega-hydroxyfatty acid esters as substrates. Several fatty acid esters were tested as inducers of LipL production. The addition of either soybean oil or a non-ionic detergent (Noigen HC) resulted in a 44 to 45-fold increase in extracellular LipL, and the presence of both resulted in a further 56-fold increase. Among the triglycerides tested, triolein was the most effective, with a 50-fold increase in LipL production. A Northern blot hybridization analysis found that the lipL transcript increased in the presence of soybean oil or Noigen HC, indicating that the production of LipL is regulated at the transcriptional level.

Steroidal Alkaloids and Stilbenoids from Veratrum taliense.

Phytochemical investigation of roots and rhizomes of Veratrum taliense yielded a new and six known steroidal alkaloids as well as a new and one reported stilbene derivative. By a combination of spectral methods (IR, MS, (1)H- and (13)C-NMR, COSY, HMQC, HMBC, and NOESY), the structure of the new alkaloid was established as 15-angeloylgermine while the known ones were identified as 15-(2-methylbutyroyl)germine, jervine, 3-veratroylzygadenine, germine, veramiline 3- O-(beta- D-glucopyranoside and stenophylline B-3- O-beta- D-glucopyranoside. The new stilbenoid, named veraphenol, was determined to be 2-(3',5'-dihydroxyphenyl)-6-hydroxybenzofuran, and the known one was shown to be resveratrol. The IN VITRO enzyme assay indicated that 3-veratroylzygadenine and resveratrol are inhibitors of xanthine oxidase. The enzyme inhibitory action of resveratrol, the most active compound found so far in V. TALIENSE, is dose-dependent with the IC (50) value at 30 microM (the IC (50) value of allopurinolused as a positive control in the study is 10 microM).

Induction of resting microglia in culture medium devoid of glycine and serine.

Cultured microglial cells usually exhibit ameboid morphology and peripheral macrophage-like properties, which are distinct from those observed in the normal mature brain. This might be caused by the inappropriate culture of microglial cells in high concentrations (approximately 200-400 microM) of Gly and Ser, although the concentrations of the amino acids in extracellular spaces of the brain parenchyma are quite low (approximately 5 microM). In the present study, we focused on the concentration-dependent effects of glycine (Gly) and serine (Ser) on microglial morphology and function. Under Gly/Ser-free and serum-free condition, the majority of rat microglial cells displayed round morphology, whereas in the presence of 5 microM Gly and 25 microM Ser, which correspond to the concentrations of Gly and Ser in the cerebrospinal fluid, they extended multiple branched processes and formed clusters of rough endoplasmic reticulum. On the other hand, Gly and Ser did not affect morphology of astrocytes. The viability of microglia was not affected by the changes in the concentrations of Gly and Ser. Metabolic activity, activities of acid phosphatase and inducible nitric oxide synthase, and superoxide anion (O2-) generation were all strongly suppressed in Gly/Ser-free medium or in medium containing physiological concentrations of both amino acids. Such activities were all enhanced in harmony with increases in the concentrations of Gly and Ser. Thus, microglial cells cultured in Gly/Ser-free medium, even though exhibiting ameboid morphology, appears to be in the functionally resting state. Furthermore, once the resting state was achieved, the microglial cells remained inactive even after the subsequent 24 h culture in serum-supplemented medium containing 400 microM of both amino acids. The medium conditioned by microglial cells that were cultured in the presence of 400 microM of Gly and Ser was toxic to cortical neurons, whereas the microglia-conditioned medium obtained in the absence of both amino acids facilitated the survival of cortical neurons. Therefore, microglial cells in the resting state, which was induced in the Gly/Ser-free condition, are likely to support neurons. Microglial cells could ramify on glass coverslips coated with astrocyte-derived extracellular matrix or on coverslips coated thinly with fibronectin and/or laminin even under the Gly/Ser-free condition. The ramified cells as induced in this way kept suppressed O2- generating activity. These findings suggest that resting ramified microglial cells with a neurotrophic activity can be induced with the combination of Gly/Ser-free medium and small amounts of extracellular matrix proteins, and that the resting state is rather stable.

What is "special" about face perception?

There is growing evidence that face recognition is "special" but less certainty concerning the way in which it is special. The authors review and compare previous proposals and their own more recent hypothesis, that faces are recognized "holistically" (i.e., using relatively less part decomposition than other types of objects). This hypothesis, which can account for a variety of data from experiments on face memory, was tested with 4 new experiments on face perception. A selective attention paradigm and a masking paradigm were used to compare the perception of faces with the perception of inverted faces, words, and houses. Evidence was found of relatively less part-based shape representation for faces. The literatures on machine vision and single unit recording in monkey temporal cortex are also reviewed for converging evidence on face representation. The neuropsychological literature is reviewed for-evidence on the question of whether face representation differs in degree or kind from the representation of other types of objects.

Giant hepatic biloma following transcatheter oily chemoembolization in a patient with hepatic metastases from malignant pheochromocytoma.

A 48-year-old woman developed hepatic metastases from malignant pheochromocytoma resected 8 years previously. Angiography revealed multiple tumor stains in the liver. Transcatheter oily chemoembolization using styrenomaleic acid neocarzinostatin and iodized oil was performed. The patient complained of severe right upper quadrant pain immediately following the transcatheter oily chemoembolization. Necrotizing cholecystitis developed on the 4th day post-transcatheter oily chemoembolization, hepatic infarction on the 12th day, and a biloma on the 19th day. Despite the administration of antibiotics and percutaneous transhepatic drainage, neither the volume of drainage nor the size of the biloma decreased. Biliary reconstruction was performed using a metallic stent, which decreased the size of the biloma.

Features and their configuration in face recognition.

Tanaka and Farah (1993) have proposed a holistic approach to face recognition in which information about the features of a face and their configuration are combined together in the face representation. An implication of the holistic hypothesis is that alterations in facial configuration should interfere with retrieval of features. In four experiments, the effect of configuration on feature recognition was investigated by creating two configurations of a face, one with eyes close together and one with eyes far apart. After subjects studied faces presented in one of the two configurations (eyes-close or eyes-far), they were tested for their recognition of features shown in isolation, in a new face configuration, and in the old face configuration. It was found that subjects recognized features best when presented in the old configuration, next best in the new configuration, and poorest in isolation. Moreover, subjects were not sensitive to configural information in inverted faces (Experiment 2) or nonface stimuli (i.e., houses; Experiments 3 and 4). Importantly, for normal faces, altering the spatial location of the eyes not only impaired subjects' recognition of the eye features but also impaired their recognition of the nose and mouth features-features whose spatial locations were not directly altered. These findings emphasize the interdependency of featural and configural information in a holistic face representation.

Protection of ischemic hippocampal neurons by ginsenoside Rb1, a main ingredient of ginseng root.

Our previous study showed that the oral administration of red ginseng powder before but not after transient forebrain ischemia prevented delayed neuronal death in gerbils, and that a neuroprotective molecule within red ginseng powder was ginsenoside Rb1. However, it remains to be clarified whether or not ginsenoside Rb1 acts directly on the ischemic brain, and the mechanism by which ginsenoside Rb1 protects the ischemic CA1 neurons is not determined. Without elucidation of the pharmacological property of ginsenoside Rb1, the drug would not be accepted as a neuroprotective agent. The present study demonstrated that the intracerebroventricular infusion of ginsenoside Rb1 after 3.5 min or 3 min forebrain ischemia, precluded significantly the ischemia-induced shortening of response latency in a step-down passive avoidance task and rescued a significant number of hippocampal CA1 neurons from lethal ischemic damage. The intracerebroventricular infusion of ginsenoside Rb1 did not affect hippocampal blood flow or hippocampal temperature except that it caused a slight increase in hippocampal blood flow at 5 min after transient forebrain ischemia. Furthermore, ginsenoside Rb1 at concentrations of 0.1-100 fg/ml (0.09-90 fM) rescued hippocampal neurons from lethal damage caused by the hydroxyl radical-promoting agent FeSO4 in vitro, and the Fenton reaction system containing p-nitrosodimethylaniline confirmed the hydroxyl radical-scavenging activity of ginsenoside Rb1. These findings suggest that the central infusion of ginsenoside Rb1 after forebrain ischemia protects hippocampal CA1 neurons against lethal ischemic damage possibly by scavenging free radicals which are overproduced in situ after brain ischemia and reperfusion. The present study may validate the empirical usage of ginseng root over thousands of years for the prevention of cerebrovascular diseases.

Effects of rat galanin and galanin message associated peptide (GMAP) on rat growth hormone secretion and stimulating effect of gamma-aminobutyric acid on galanin release from rat hypothalamus.

Immunoreactive galanin and galanin message associated peptide (GMAP) were detectable in rat hypothalamus in the concentration of 563 +/- 23 and 14.3 +/- 3.1 fmol/hypothalamus, respectively. gamma-Aminobutyric acid (GABA) elicited a dose-related increase in galanin release from rat hypothalamic fragments, which was inhibited by picrotoxin, a GABA antagonist. Growth hormone (GH) secretion from rat anterior pituitary cells were stimulated by rat galanin, but not by GMAP. These findings suggest that hypothalamic galanin, but not GMAP, may play roles in GH secretion induced by GABAergic mechanisms in the rat.

Glucocorticoid- and mineralocorticoid receptors in microglial cells: the two receptors mediate differential effects of corticosteroids.

Effects of steroid hormones on the regulation of function and morphology of microglial cells were investigated using the cultured cells isolated from forebrain of newborn rats. Cortisol, corticosterone, and aldosterone at 100 nM caused a strong shrinkage of microglial cells cultured in a serum-supplemented medium. However, cholesterol, pregnenolone, testosterone, estradiol, and dehydroepiandrosterone did not exhibit any significant effects. The corticosteroids also inhibited the GM-CSF-mediated ramification of microglia in a serum-free medium. An anti-glucocorticoid agent RU38486 abolished the effects of corticosteroids on the microglial morphology, suggesting the presence of functional glucocorticoid receptor (GR) in microglial cells. The presence of GR was confirmed by immunoblotting with an antibody to the receptor. Cytokines GM-CSF and interleukin-3 altered the level of GR expression. Binding experiments with [3H]-corticosterone demonstrated the presence of not only GR but also mineralocorticoid receptor (MR): the dissociation constants (Kd) and the number of binding sites (Bmax) were 0.8 nM and 15 fmol/mg protein for MR and 5.0 nM and 73 fmol/mg protein for GR, respectively. The pure glucocorticoid RU28362 and dexamethasone at 20 nM (but not aldosterone and corticosterone at the same concentration) inhibited proliferation of microglial cells, as revealed by PCNA immunocytochemistry. RU28362 inhibited the activities of inducible nitric oxide synthase and acid phosphatase at concentrations higher than 1 nM. Aldosterone and corticosterone exhibited the similar inhibitory effect at 100 nM, and this inhibition was completely overcome by RU38486. On the other hand, corticosterone and aldosterone at concentrations lower than 1 nM enhanced the activities of both enzymes. The antimineralocorticoid agent spironolactone eliminated the stimulatory effects of corticosterone on the enzyme activities. In accordance with these biochemical results, electron microscopic observations revealed that glucocorticoids enhanced the formation of lysosomal vacuolation in microglial cells and aldosterone increased the number and size of lysosomes. In conclusion, it is suggested that GR and MR mediated the opposite effects of corticosterone on the functions of microglial cells; the hormone acted as an inhibitor through GR and as an stimulator through MR.

Vomiting induction by ipecac syrup in dogs and ferrets.

The dog has been used as an experimental animal in emesis research. In this study, we analyzed the emetic effects of ipecac syrup using a smaller animal, the ferret, and compared its response to that of the dog. Dogs and ferrets were divided into 4 groups (n = 4, each). Each group was given either 0.1, 0.25, 0.5, or 1.0 ml/kg of ipecac syrup, and the latency and numbers of retching and vomiting were recorded. Animals given an equal volume of saline served as controls. The numbers of vomiting and retching increased dose-dependently in both dogs and ferrets, and there was no difference in latency and numbers of vomiting between them. The numbers of retching were greater in ferrets than in dogs at > or = 0.25 ml/kg. Taking these results into consideration, the ferret seems to be as useful as the dog in studies on emetic effects of ipecac syrup.

Inhibitory effect of acetylshikonin on the activation of NADPH oxidase in polymorphonuclear leukocytes in both whole cell and cell-free systems.

The effects of acetylshikonin (AS) on the activation of NADPH oxidase (EC 1.6.99.6) in guinea pig polymorphonuclear leukocytes (PMNs) in both whole cell and cell-free activation systems were investigated. When PMNs were treated with AS before exposure to phorbol myristate acetate (PMA), superoxide (O2-) generation in these cells was significantly reduced, but after exposure of PMNs to PMA, inhibition of O2- generation by AS did not occur. Thiol compounds completely abolished the inhibitory effect of AS on the O2- generating activity of PMNs. In the cell-free system, AS inhibited the activation of NADPH oxidase induced by myristate in a combination of cytosol and membrane fractions obtained from intact PMNs, but did not inhibit the activity of NADPH oxidase already induced. These results suggest that AS inhibits the generation of NADPH oxidase complex in the activation of respiratory burst of PMNs, but does not directly inhibit the activity of NADPH oxidase already generated.

Involvement of pituitary adenylate cyclase-activating polypeptide in growth hormone secretion induced by serotoninergic mechanisms in the rat.

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) stimulated GH secretion in superfused rat anterior pituitary cell in vitro and in conscious male rats in vivo. PACAP-38-induced GH secretion was inhibited by PACAP-(6-38), an N-terminal-deleted analog, at 100-fold concentrations of PACAP-38 both in vitro and in vivo. In contrast, a GH-releasing hormone antagonist did not affect the action of PACAP-38 to stimulate GH release in vitro. Plasma GH increase induced by i.v. injection of 5-hydroxy-L-tryptophan (1 mg/100 g BW), a precursor of serotonin, was blunted by PACAP-(6-38) (1 nmol/100 g BW, i.v.), whereas spontaneous pulsatile GH secretion in conscious male rats, which is governed by hypothalamic GH-releasing hormone and somatostatin, was not affected by repeated i.v. injection of PACAP-(6-36). These findings suggest that PACAP-(6-38) is a potent antagonist of PACAP-38 to stimulate GH secretion both in vivo and in vitro. Taken together with the facts that PACAP-38 is highly concentrated in the hypothalamus and that is released into the hypophysial portal blood, our present findings suggest that PACAP-38 might play a stimulatory role on GH secretion induced by serotoninergic mechanisms in the rat.