Lonicera japonica extends lifespan and healthspan in Caenorhabditis elegans.

Lonicera japonica (LJ) is widely used as the local medicine to improve body and prevent ills in China, but mechanisms of its healthy beneficial effects remain largely unclear. Here, we evaluated the anti-aging and healthspan promoting activities of 75% ethanol extract of LJ (LJ-E) in the animal model Caenorhabditis elegans. Our results showed that LJ-E (500 µg/mL) treatment enhanced the mean lifespan of worms by over 21.87% and significantly improved age-associated physiological functions in C. elegans. The 500 µg/mL concentration of LJ-E enhanced the survival rates under oxidative and thermal stresses, and decreased reactive oxygen species (ROS) levels and fat accumulation in the worms. Gene-specific mutant studies showed that LJ-E-mediated lifespan extension was dependent on mev-1, daf-2, daf-16, and hsf-1, but not eat-2 genes. LJ-E could upregulate stress-inducible genes, viz., hsp-16.2, sod-3 and mtl-1. Moreover, we found that the D1086.10 protein interacted with superoxide dismutase (SOD)-3 by functional protein association networks analysis according to RNA-sequencing results. It was confirmed that D1086.10 was needed to promote longevity, and positively regulated expression of sod-3 by using D1086.10 mutants. Furthermore, LJ-E significantly delayed amyloid ß-protein induced paralysis in CL4176 strain. Given the important role of autophagy in aging and protein homeostasis, we observed that LJ-E could remarkably increase the mRNA expression of autophagy gene bec-1 in CL4176 strain, and decrease expression of autophagy substrate p62 protein by more than 40.0% in BC12921 strain. Finally, we found that combination composed of three major compounds (54 µg/mL chlorogenic acid, 15 µg/mL 1,5-dicaffeoylquinic acid and 7.5 µg/mL 1,3-dicaffeoylquinic acid) of 500 µg/mL LJ-E could significantly delay paralysis in CL4176 worms caused by Aß toxicity, comparable to that of LJ-E. Overall, our study may have important implications in using Lonicera japonica to promote healthy aging and have a potency to design therapeutics for age-related diseases.

Cratoxylum formosum Extract Protects against Amyloid-Beta Toxicity in a Caenorhabditis elegans Model of Alzheimer's Disease.

Amyloid-ß, one of the hallmarks of Alzheimer's disease, is toxic to neurons and causes cell death in the brain. Oxidative stress is known to play an important role in Alzheimer's disease, and there is strong evidence linking oxidative stress to amyloid-ß. The herbal plant "Tiew kon" (Cratoxylum formosum ssp. pruniflorum) is an indigenous vegetable that is grown in Southeast Asia. Many reports suggested that the twig extract from C. formosum possesses an antioxidant property. The purpose of this study was to investigate the protective effect of the twig extract from C. formosum against amyloid-ß toxicity using the transgenic Caenorhabditis elegans model. This study demonstrated that the extract significantly delayed amyloid-ß-induced paralysis in the C. elegans model of Alzheimer's disease. Using a genetic approach, we found that DAF-16/FOXO transcription factor, heat shock factor 1, and SKN-1 (Nrf2 in mammals) were required for the extract-mediated delayed paralysis. The extract ameliorated oxidative stress by reducing the level of H2O2, which appeared to account for the protective action of the extract. The extract possesses antioxidant activity against juglone-induced oxidative stress as it was shown to increase survival of the stressed worms. In addition, C. formosum decreased the expression of the heat shock protein-16.2 gene which was induced by thermal stress, indicating its ability to reduce cellular stress. The results from this study support the C. elegans model in the search for disease-modifying agents to treat Alzheimer's disease and indicate the potential of the extract from C. formosum ssp. pruniflorum as a source for the development of anti-Alzheimer's drugs.

Prophylaxis Versus Treatment Use of Laxative for Paralysis of Lower Gastrointestinal Tract in Critically Ill Patients.

GOALS: To evaluate the prevalence of lower gastrointestinal tract paralysis and to compare the success to achieve defecation between treatment and prophylaxis strategies. BACKGROUND: Laxatives use is commonly the first-level measure to achieve defecation in critically ill patients with lower gastrointestinal tract paralysis. Studies comparing prophylaxis versus treatment of lower gastrointestinal tract paralysis have not been performed yet. STUDY: We designed 3 sequential phases of 4 months each: observational phase, treatment phase, and prophylaxis phase. First-level measure was intermittent polyethylene glycol (PEG) 4000 by nasogastric tube. Second-level measures were enema, neostigmine, and continuous PEG. Primary endpoints were the prevalence of constipation for the observational phase and the number of patients that failed to achieve defecation with first-level measures for the treatment and prophylaxis phases. RESULTS: Paralysis of lower gastrointestinal tract in the observational phase was found in 57 of 63 patients (90.5%). Failure to achieve defecation with the first-level measure occurred in 16 of 64 patients (25%) in the treatment phase and in 6 of 70 patients (8.6%) in the prophylaxis phase (P=0.01). Eighteen measures of second level were applied in the treatment phase and 6 in the prophylaxis phase. CONCLUSIONS: Paralysis of the lower gastrointestinal tract in mechanically ventilated ICU patients is common. PEG given as prophylaxis on the first day after mechanical ventilation is associated with faster resolution of paralysis of gastrointestinal tract than PEG given as a treatment on day 4.

A Cultivated Form of a Red Seaweed (Chondrus crispus), Suppresses ß-Amyloid-Induced Paralysis in Caenorhabditis elegans.

We report here the protective effects of a methanol extract from a cultivated strain of the red seaweed, Chondrus crispus, against ß-amyloid-induced toxicity, in a transgenic Caenorhabditis elegans, expressing human Aß1-42 gene. The methanol extract of C. crispus (CCE), delayed ß-amyloid-induced paralysis, whereas the water extract (CCW) was not effective. The CCE treatment did not affect the transcript abundance of amy1; however, Western blot analysis revealed a significant decrease of Aß species, as compared to untreated worms. The transcript abundance of stress response genes; sod3, hsp16.2 and skn1 increased in CCE-treated worms. Bioassay guided fractionation of the CCE yielded a fraction enriched in monogalactosyl diacylglycerols (MGDG) that significantly delayed the onset of ß-amyloid-induced paralysis. Taken together, these results suggested that the cultivated strain of C. crispus, whilst providing dietary nutritional value, may also have significant protective effects against ß-amyloid-induced toxicity in C. elegans, partly through reduced ß-amyloid species, up-regulation of stress induced genes and reduced accumulation of reactive oxygen species (ROS).

Using acupoint-to-acupoint penetrative needling to treat post-stroke spastic paralysis: a clinical progress review.

OBJECTIVE: To determine the characteristics and advantages of acupoint-to-acupoint penetrative needling (AAPN) treatment for post-stroke spastic paralysis (PSSP) to improve the clinical outcomes of this disease in the future. METHODS: Randomized, controlled trials of PSSP patients receiving AAPN treatment were searched from MEDLINE, EMBASE, and China National Knowledge Infrastructure Database between January 2006 and June 2013. Key words included: clinic or clinical, acupuncture, needling, acupoint-to-acupoint, penetrative or penetration or penetrating, stroke or apoplexy or cerebral infarction or cerebral hemorrhage, spastic paralysis or spasticity or palsy, and hypermyotonia. Language was limited to English and Chinese. Case series reports, review articles, and, animal studies were excluded. RESULTS: AAPN showed better clinical results on PSSP than other acupuncture treatments, especially when combined with adjunct therapies such as electroacupuncture, bloodletting, and rehabilitation. The greatest benefit was achieved with rehabilitation combined with penetration from Yang-channel acupoints to Yin-channel acupoints in the upper limbs, and from Yin-channel acupoints to Yang-channel acupoints in the lower limbs with a reinforcing maneuver. CONCLUSION: AAPN is an effective treatment for PSSP, and it can accelerate and enhance functional repair of PSSP patients.

Green tea aroma fraction reduces ß-amyloid peptide-induced toxicity in Caenorhabditis elegans transfected with human ß-amyloid minigene.

Green tea is a popular world-wide beverage with health benefits that include preventive effects on cancer as well as cardiovascular, liver and Alzheimer's diseases (AD). This study will examine the preventive effects on AD of a unique aroma of Japanese green tea. First, a transgenic Caenorhabditis elegans (C. elegans) CL4176 expressing human ß-amyloid peptide (Aß) was used as a model of AD. A hexane extract of processed green tea was further fractionated into volatile and non-volatile fractions, named roasty aroma and green tea aroma fractions depending on their aroma, by microscale distillation. Both hexane extract and green tea aroma fraction were found to inhibit Aß-induced paralysis, while only green tea aroma fraction extended lifespan in CL4176. We also found that green tea aroma fraction has antioxidant activity. This paper indicates that the green tea aroma fraction is an additional component for prevention of AD.

Clinical experience with a novel electromyographic approach to preventing phrenic nerve injury during cryoballoon ablation in atrial fibrillation.

BACKGROUND: Phrenic nerve palsy remains the most frequent complication associated with cryoballoon-based pulmonary vein (PV) isolation. We sought to characterize our experience using a novel monitoring technique for the prevention of phrenic nerve palsy. METHODS AND RESULTS: Two hundred consecutive cryoballoon-based PV isolation procedures between October 2010 and October 2013 were studied. In addition to standard abdominal palpation during right phrenic nerve pacing from the superior vena cava, all patients underwent diaphragmatic electromyographic monitoring using surface electrodes. Cryoablation was terminated on any perceived reduction in diaphragmatic motion or a 30% decrease in the compound motor action potential (CMAP). During right-sided ablation, a ≥30% reduction in CMAP amplitude occurred in 49 patients (24.5%). Diaphragmatic motion decreased in 30 of 49 patients and was preceded by a 30% reduction in CMAP amplitude in all. In 82% of cases, this reduction in CMAP amplitude occurred during right superior PV isolation. The baseline CMAP amplitude was 946.5±609.2 mV and decreased by 13.8±13.8% at the end of application. This decrease was more marked in the 33 PVs with a reduction in diaphragmatic motion than in those without (40.9±15.3% versus 11.3±10.5%; P<0.001). In 3 cases, phrenic nerve palsy persisted beyond the end of the procedure, with all cases recovering within 6 months. Despite the shortened application all veins were isolated. At repeat procedure the right-sided PVs reconnected less frequently than the left-sided PVs in those with phrenic nerve palsy. CONCLUSIONS: Electromyographic phrenic nerve monitoring using the surface CMAP is reliable, easy to perform, and offers an early warning to impending phrenic nerve injury.

Amyloid-beta (Aß1₋42)-induced paralysis in Caenorhabditis elegans is inhibited by the polyphenol quercetin through activation of protein degradation pathways.

SCOPE: Dietary polyphenols are suggested to play a role in the prevention of Alzheimer's disease, of which accumulation of aggregated beta amyloid (Aß) is a key histopathological hallmark. We used the transgenic Caenorhabditis elegans strain CL2006, which expresses human Aß1₋42 under control of a muscle-specific promoter and responds to Aß1₋42 aggregation with paralysis, to test effects of the polyphenol quercetin on the phenotype. METHODS AND RESULTS: Quercetin dose-dependently decreased the amount of aggregated proteins in solution and also paralysis in CL2006. The knockdown of key components of unfolded protein response in mitochondria or the endoplasmic reticulum by RNA-interference (RNAi) enhanced paralysis in CL2006 but did not prevent the paralysis reducing activities of quercetin. RNAi for essential members of proteasomal protein degradation or macroautophagy also significantly increased paralysis but prevented quercetin from being effective. Quercetin increased proteasomal activity and, moreover, enhanced the flow of proteins through the macroautophagy pathway as reflected by reduced lysosome staining. CONCLUSION: The proteostasis network, including unfolded protein response, defines the aggregation of Aß1₋42 and the associated paralysis phenotype in a nematode model for Alzheimer's disease. The polyphenol quercetin, by specifically activating macroautophagy and proteasomal degradation pathways, proved able to prevent Aß1₋42 agregation and paralysis.

Vellozia flavicans Mart. ex Schult. hydroalcoholic extract inhibits the neuromuscular blockade induced by Bothrops jararacussu venom.

BACKGROUND: Snakebite is a significant public health issue in tropical countries. In Brazil, some of the most common snake envenomations are from Bothrops. Bothrops bites trigger local and systemic effects including edema, pain, erythema, cyanosis, infections, and necrosis. Vellozia flavicans is a plant from the Brazilian "cerrado" (savanna) that is popularly used as an anti-inflammatory medicine. Since inflammation develops quickly after Bothrops bites, which can lead to infection, the aim of the present study was to observe possible anti-snake venom and antimicrobial activities of V. flavicans (Vf). METHODS: The chromatographic profile of the main constituents from the Vf leaf hydroalcoholic extract was obtained by thin-layer chromatography (TLC). The anti-snake venom activity was measured by Vf's ability to neutralize the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu) in a mouse phrenic nerve-diaphragm model (PND). After a 20 min incubation, preparations of PND were added to Tyrode's solution (control); Vf (0.2, 0.5, 1, and 2 mg/mL); 40 µg/mL Bjssu; pre-incubation for 30 min with Bjssu and 1 mg/mL Vf; and a Bjssu pretreated preparation (for 10 min) followed by 1 mg/mL Vf. Myographic recording was performed, and the contractile responses were recorded. The antimicrobial activity (minimum inhibitory concentration [MIC] and minimum bactericidal concentration [MBC]) was obtained for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis, using gentamicin and vancomycin as positive controls. RESULTS: TLC analysis yielded several compounds from Vf, such as flavonoids (quercetin) and phenolic acids (chlorogenic acid). Bjssu completely blocked the contractile responses of PND preparations, while Vf preserved 97% (±10%) of the contractile responses when incubated with Bjssu. In the PND pretreated with Bjssu, Vf was able to inhibit the neuromuscular blockade progress. MIC and MBC of Vf ranged from 2.5 to 5.0 mg/mL for P. aeruginosa and S. aureus strains, while no antimicrobial activity was observed for E. coli and E. faecalis. CONCLUSIONS: The hydroalcoholic extract from Vf leaves was able to neutralize and decrease the in vitro neuromuscular blockade caused by Bjssu. However, it did not show significant antimicrobial activity against the tested bacteria.

Stroke rehabilitation using noninvasive cortical stimulation: motor deficit.

Noninvasive cortical stimulation (NICS) has been used during the acute, postacute and chronic poststroke phases to improve motor recovery in stroke patients having upper- and/or lower-limb paresis. This paper reviews the rationale for using the different NICS modalities to promote motor stroke rehabilitation. The changes in cortical excitability after stroke and the possible mechanisms of action of cortical stimulation in this context are outlined. A number of open and placebo-controlled trials have investigated the clinical effect of repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) of the primary motor cortex in patients with motor stroke. These studies attempted to improve motor performance by increasing cortical excitability in the stroke-affected hemisphere (via high-frequency rTMS or anodal tDCS) or by decreasing cortical excitability in the contralateral hemisphere (via low-frequency rTMS or cathodal tDCS). The goal of these studies was to reduce the inhibition exerted by the unaffected hemisphere on the affected hemisphere and to then restore a normal balance of interhemispheric inhibition. All these NICS techniques administered alone or in combination with various methods of neurorehabilitation were found to be safe and equally effective at the short term on various aspects of poststroke motor abilities. However, the long-term effect of NICS on motor stroke needs to be further evaluated before considering the use of such a technique in the daily routine management of stroke.

Anthelmintic and relaxant activities of Verbascum Thapsus Mullein.

BACKGROUND: Verbascum thapsus is used in tribal medicine as an antispasmodic, anti-tubercular agent and wormicide. In this study, we investigated the antispasmodic and anthelmintic activities of crude aqueous methanolic extract of the plant. METHODS: V. thapsus extracts were tested against roundworms (Ascaridia galli) and tapeworms (Raillietina spiralis). Each species of worm was placed into a negative control group, an albendazole treatment group, or a V. thapsus treatment group, and the time taken for paralysis and death was determined. In addition, relaxation activity tests were performed on sections of rabbit's jejunum. Plant extracts were tested on KCl-induced contractions and the relaxation activities were quantified against atropine. V. thapsus calcium chloride curves were constructed to investigate the mode of action of the plant extracts. RESULTS: We detected flavonoids, saponins, tannins, terpenoids, glycosides, carbohydrates, proteins, fats and fixed oils in V. thapsus. For both species of worm, paralysis occurred fastest at the highest concentration of extract. The relative index values for paralysis in A. galli were 4.58, 3.41 and 2.08, at concentrations of 10, 20 and 40 mg/ml of plant extract, respectively. The relative index for death in A. galli suggested that V. thapsus extract is wormicidal at high concentration. Similarly, the relative indexes for paralysis and death in R. spiralis suggested that the extract is a more potent wormicidal agent than albendazole. The mean EC(50) relaxation activity values for spontaneous and KCl induced contractions were 7.5 ± 1.4 mg/ml (6.57-8.01, n = 6) and 7.9 ± 0.41 mg/ml (7.44-8.46, n = 6), respectively. The relaxation activity of the extract was 11.42 ± 2, 17.0 ± 3, 28.5 ± 4, and 128.0 ± 7% of the maximum observed for atropine at corresponding concentrations. The calcium chloride curves showed that V. thapsus extracts (3 mg/ml), had a mean EC(50) (log molar [calcium]) value of -1.9 ± 0.06 (-1.87 - -1.98, n = 6) vs. control EC(50) = -2.5 ± 0.12 (-2.37 - -2.56, n = 6), whereas the verapamil (0.1 µM) EC(50) was -1.7 ± 0.1 (-1.6 - -1.8, n = 6) vs. control EC(50) = -2.4 ± 0.09 (-2.3 - -2.47, n = 5). CONCLUSIONS: Our results suggest that V. thapsus, which is currently used by some tribes in the Malakand region of Pakistan, has anthelmintic and antispasmodic value.

Antithrombotic activity of argan oil: an in vivo experimental study.

OBJECTIVE: Argan oil has been shown to inhibit in vitro and ex vivo platelet aggregation without extending bleeding time. In this report, we examined in vivo the antithrombotic activity of argan oil in an experimental thrombosis model in mice: acute pulmonary thromboembolism and in vitro its effect in a coagulation assay. METHODS: Acute pulmonary thromboembolism was induced, after argan oil treatment, by an intravenous injection of a collagen and epinephrine mixture. The paralyzed and dead mice in each group were numbered and the percentage of protection against acute pulmonary thromboembolism was calculated. The histologic study was conducted in lung tissue to estimate the percentage of opened and occluded vessels by platelet thrombi. The coagulation assay was monitored in platelet-poor plasma from normal rats by measuring the clotting parameters (activated partial thromboplastin time, prothrombin time, and thrombin time) in the presence and absence of argan oil. RESULTS: Argan oil (1 mL/100 g/day), administered orally, showed an antithrombotic activity preventing the paralysis or death (50%) induced by the collagen-epinephrine intravenous injection. This observation was confirmed by the lung histologic examination, in which the density of occluded blood vessels was significantly decreased (62.16 ± 3.95%). However, the argan oil remained inactive for the coagulation parameters of activated partial thromboplastin time, prothrombin time, and thrombin time at variance with heparin, an anticoagulant reference drug. The antithrombotic activity of argan oil seemed unrelated to the anticoagulant activity. CONCLUSION: We suggest that argan oil might be an interesting natural dietary source for the nutritional prevention of hemostasis and cardiovascular disorders. Clinical trials would be necessary and relevant to confirm this hypothesis.

Cinnamomum cassia bark in two herbal formulas increases life span in Caenorhabditis elegans via insulin signaling and stress response pathways.

BACKGROUND: Proving the efficacy and corresponding mode of action of herbal supplements is a difficult challenge for evidence-based herbal therapy. A major hurdle is the complexity of herbal preparations, many of which combine multiple herbs, particularly when the combination is assumed to be vitally important to the effectiveness of the herbal therapy. This issue may be addressed through the use of contemporary methodology and validated animal models. METHODS AND PRINCIPAL FINDINGS: In this study, two commonly used traditional herbal formulas, Shi Quan Da Bu Tang (SQDB) and Huo Luo Xiao Ling Dan (HLXL) were evaluated using a survival assay and oxidative stress biomarkers in a well-established C. elegans model of aging. HLXL is an eleven herb formula modified from a top-selling traditional herbal formula for the treatment of arthritic joint pain. SQDB consists of ten herbs often used for fatigue and energy, particularly in the aged. We demonstrate here that SQDB significantly extend life span in a C. elegans model of aging. Among all individual herbs tested, two herbs Cinnamomum cassia bark (Chinese pharmaceutical name: Cinnamomi Cortex, CIN) and Panax ginseng root (Chinese pharmaceutical name: Ginseng Radix, GS) significantly extended life span in C. elegans. CIN in both SQDB and HLXL formula extended life span via modulation of multiple longevity assurance genes, including genes involved in insulin signaling and stress response pathways. All the life-span-extending herbs (SQDB, CIN and GS) also attenuated levels of H2O2 and enhanced small heat shock protein expression. Furthermore, the life span-extending herbs significantly delayed human amyloid beta (Abeta)-induced toxicity in transgenic C. elegans expressing human Abeta. CONCLUSION/SIGNIFICANCE: These results validate an invertebrate model for rapid, systematic evaluation of commonly used Chinese herbal formulations and may provide insight for designing future evidence-based herbal therapy(s).

Heat shock treatment reduces beta amyloid toxicity in vivo by diminishing oligomers.

Heat shock response, mediated by heat shock proteins, is a highly conserved physiological process in multicellular organisms for reestablishment of cellular homeostasis. Expression of heat shock factors and subsequent heat shock protein plays a role in protection against proteotoxicity in invertebrate and vertebrate models. Proteotoxicity due to beta-amyloid peptide (Abeta) oligomerization has been linked to the pathogenesis of Alzheimer's disease. Previously, we demonstrated that progressive paralysis induced by expression of human Abeta(1-42) in transgenic Caenorhabditis elegans was alleviated by Abeta oligomer inhibitors Ginkgo biloba extract and its constituents [Wu, Y., Wu, Z., Butko, P., Christen, Y., Lambert, M.P., Klein, W.L., Link, C.D., Luo, Y., 2006. Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans. J. Neurosci. 26(50): 13102-13113]. In this study, we apply a protective heat shock to the transgenic C. elegans and demonstrate: (1) a delay in paralysis, (2) increased expression of small heat shock protein HSP16.2, and (3) significant reduction of Abeta oligomers in a heat shock time-dependent manner. These results suggest that transient heat shock lessens Abeta toxicity by diminishing Abeta oligomerization, which provides a link between up regulation of endogenous chaperone proteins and protection against Abeta proteotoxicity in vivo.

Raising parents' awareness of the benefits of immunization by using a visual aid tool.

A visual aid tool was used in two communities of Chad to raise parents' awareness of the benefits of immunization. In one community, the tool was administered by social workers two weeks before national immunization days (NIDs) and in the other community by vaccinators during NIDs. Parents' awareness significantly rose in both communities but was more significant in the community where the tool was administered by social workers. A significant association was found between parents' unawareness and children who missed immunization in both communities.

Limited effects of glatiramer acetate in the high-copy number hSOD1-G93A mouse model of ALS.

In amyotrophic lateral sclerosis (ALS), an involvement of the immune system in the degenerative processes has been shown in both humans and the transgenic SOD1-G93A mice. We previously showed that Glatiramer acetate (also known as copolymer-1; COP-1; Copaxone) improves motor function and extends survival times in an inbred strain of ALS mice probably by interacting with pro-inflammatory T(H) lymphocytes. In the course of this study we tested whether these beneficial effects could be reproduced by repeated vaccination of animals with COP-1 without co-administration of complete Freund's adjuvant. In an outbred strain we could not demonstrate a positive effect of COP-1 on survival times, but found a significant improvement of motor performance during the late stage of disease and a moderate decrease of the production of the inflammatory cytokines interferon-gamma and IL-4 by T lymphocytes isolated from the mice's spleen. In conclusion, the effects of COP-1 in the applied hybrid strain displaying a faster disease progression were less pronounced than in the earlier tested inbred strain of ALS mice.

Soy isoflavone glycitein protects against beta amyloid-induced toxicity and oxidative stress in transgenic Caenorhabditis elegans.

BACKGROUND: Epidemiological studies have associated estrogen replacement therapy with a lower risk of developing Alzheimer's disease, but a higher risk of developing breast cancer and certain cardiovascular disorders. The neuroprotective effect of estrogen prompted us to determine potential therapeutic impact of soy-derived estrogenic compounds. Transgenic C. elegans, that express human beta amyloid (Abeta), were fed with soy derived isoflavones genistein, daidzein and glycitein (100 microg/ml) and then examined for Abeta-induced paralysis and the levels of reactive oxygen species. RESULTS: Among the three compounds tested, only glycitein alleviated Abeta expression-induced paralysis in the transgenic C. elegans. This activity of glycitein correlated with a reduced level of hydrogen peroxide in the transgenic C. elegans. In vitro scavenging effects of glycitein on three types of reactive oxygen species confirmed its antioxidant properties. Furthermore, the transgenic C. elegans fed with glycitein exhibited reduced formation of beta amyloid. CONCLUSION: These findings suggest that a specific soy isoflavone glycitein may suppress Abeta toxicity through combined antioxidative activity and inhibition of Abeta deposition, thus may have therapeutic potential for prevention of Abeta associated neurodegenerative disorders.

Prophylactic hyperbaric oxygen treatment and rat spinal cord re-irradiation.

Normal tissue injury may lead to severe, life threatening, late side effects after therapeutic use of irradiation. Neurological complications caused by radiation of the spinal cord are ascribed to progressive, irreversible damage to the vasculature. Hyperbaric oxygen (HBO) is known to induce angiogenesis in irradiated tissue and has been proven to reduce late radiation injury in several normal tissues when applied during the latent period before complications become manifest. In the present study: (1). the prophylactic potential of HBO; (2). optimal timing of HBO therapy after spinal cord irradiation, i.e. during the latent period; and (3). effect of HBO on the re-irradiation tolerance of the spinal cord were investigated. The rat cervical spinal cord was locally X-ray irradiated with ten fractions of 6.5 Gy in 11 days. Five treatment groups (n=10) included: irradiation alone and irradiation followed by 30 HBO treatments (100% oxygen at 240 kPa for 90 min) during latency, with HBO starting either immediately, 5, 10 or 15 weeks after the primary irradiation course. One year after the primary treatment, the same spinal cord volume was re-irradiated with 20 Gy single dose. During life span, the animals were observed on the incidence of myelitis and the duration of the latent period. The actuarial analysis revealed no significant difference in neurological complications free survival between the irradiation alone and the irradiation+HBO treatment groups. A tendency towards radiosensitization was found in the group in which the primary irradiation course was immediately followed by the HBO treatment course. The data show that HBO applied during the latent period of progressively developing irradiation damage to the spinal cord does not increase the re-irradiation tolerance of this tissue.

A mechanism of the thearubigin fraction of black tea (Camellia sinensis) extract protecting against the effect of tetanus toxin.

The aim of the present study was to elucidate the mechanism of the protective effect of black tea extract's thearubigin fraction against the action of tetanus toxin. The effects of thearubigin fraction extracted from a black tea infusion were examined for neuromuscular blocking action on tetanus toxin in mouse phrenic nerve-diaphragm preparations and on the binding of this toxin to the synaptosomal membrane preparations of rat cerebral cortices. The interaction between tetanus toxin and thearubigin fraction was also investigated. Tetanus toxin (4 micrograms/ml) abolished indirect twitches in mouse phrenic nerve-diaphragm preparations within 150 min. Thearubigin fraction mixed with tetanus toxin blocked the inhibitory effect of the toxin. Mixing iodinated toxin with thearubigin fraction inhibited the specific binding of [125I]tetanus toxin to the synaptosomal membrane preparation. The effects of thearubigin fraction were dose-dependent. The elution profile of [125I]tetanus toxin on Sephadex G-50 column chromatography was different from that of toxin mixed with thearubigin fraction. These findings indicate that thearubigin fraction protects against the action of tetanus toxin by binding with the toxin.

An ecological paradigm for a health behavior analysis of "konzo", a paralytic disease of Zaire from toxic cassava.

Konzo is an irreversible paralytic disease afflicting tens of thousands of women and children in rural Zaire and throughout sub-Sahara Africa. The disease can occur where bitter, high-yield varieties of cassava that thrive in arid soils provide the basic nutritional staple. The paraparesis is related to upper motor neuron damage stemming from the consumption of insufficiently processed toxic cassava roots (manioc) and a diet poor in the sulfur-based amino acids necessary for the body to detoxify the cyanide in this plant. The ecological paradigm [Kelly (1968) Toward an ecological conception of preventive interventions, in Research Contributions from Psychology to Community Mental Health, ed. J. W. Carter, pp. 75-99, Behavioral Publications, New York] is adapted as the evaluative model for evaluating the potential effectiveness of a proposed health behavior/education intervention for konzo. This qualitative research model involves a consideration of the cycling of resources (human labor and material), adaptation (of personal and social practices related to the health issue), succession (of social institutions, values, customs), interdependence (of human social units), and feasibility (or the congruency of the proposed intervention and cultural traits of the host environment). Based on this evaluative model, a health behavior/education level of intervention focusing specifically on using focus groups and multichannel communication techniques to discourage unsafe manioc short-soaking tendencies among village women farmers seems feasible. Such an approach is not dependent on sophisticated technical or material inputs and is therefore readily sustainable without outside agency support once it is effectively initiated within that culture.