Preservation of fruit and vegetable discards with sodium metabisulfite.

Two series of experiments were performed to investigate the aerobic preservation of fruit and vegetable discards (FVD) using sodium metabisulfite (SMB). In Exp. 1, metabisulfite was applied at 0, 2, 4, 6, and 8 g/kg FVD for 0, 3, 6, 9, and 12 d. Metabisulfite treatment at 6 and 8 g/kg FVD was highly effective in controlling putrefaction and preserving the nutrient components for 6 and 9 d, respectively. In the pilot-scale experiment (Exp. 2), SMB was applied at 0 and 8 g/kg FVD in a 600-L bucket for 0, 6, and 9 d in an outdoor environment. The SMB treatment was highly effective in maintaining the integrity and freshness of FVD, suppressing microbial proliferation, and preserving the nutrient constituents. Under the conditions of this study, SMB effectively preserved FVD in an aerobic environment, enabling their more efficient long-term recycling through livestock feed or development of value-added products.

Viral vector-based improvement of optic nerve regeneration: characterization of individual axons' growth patterns and synaptogenesis in a visual target.

Lack of axon growth ability in the central nervous system poses a major barrier to achieving functional connectivity after injury. Thus, a non-transgenic regenerative approach to reinnervating targets has important implications in clinical and research settings. Previous studies using knockout (KO) mice have demonstrated long-distance axon regeneration. Using an optic nerve injury model, here we evaluate the efficacy of viral, RNA interference (RNAi) and pharmacological approaches that target the phosphatase and tensin homolog (PTEN) and signal transducer and activator of transcription-3 pathways to improve long-distance axon regeneration in wild-type mice. Our data show that adeno-associated virus (AAV) expressing short hairpin RNA (shRNA) against PTEN (shPTEN) enhances retinal ganglion cell axon regeneration after crush injury. However, compared with the previous data in PTEN KO mice, AAV-shRNA results in a lesser degree of regeneration, likely due to incomplete gene silencing inherent to RNAi. In comparison, an extensive enhancement in regeneration is seen when AAV-shPTEN is coupled to AAV encoding ciliary neurotrophic factor (CNTF) and to a cyclic adenosine monophosphate (cAMP) analog, allowing axons to travel long distances and reach their target. We apply whole-tissue imaging that facilitates three-dimensional visualization of single regenerating axons and document heterogeneous terminal patterns in the targets. This shows that some axonal populations generate extensive arbors and make synapses with the target neurons. Collectively, we show a combinatorial viral RNAi and pharmacological strategy that improves long-distance regeneration in wild-type animals and provide single fiber projection data that indicates a degree of preservation of target recognition.

Comparison of diagnostic methods for onychomycosis, and proposal of a diagnostic algorithm.

BACKGROUND: Traditionally, the gold standard for diagnosis of onychomycosis has been the combination of direct microscopy with potassium hydroxide (KOH) staining and fungal culture. However, several studies have suggested that periodic-acid-Schiff (PAS) staining of nail-plate clippings may be a very sensitive method for the diagnosis of onychomycosis. AIM: To compare the sensitivities of direct microscopy with KOH, fungal culture and PAS staining of nail-plate clippings, and to define an efficient, high-yield and cost-effective diagnostic strategy for the diagnosis of onychomycosis in the clinical setting. METHODS: We evaluated a total of 493 patients with clinically suspected onychomycosis. Group A comprised 400 patient samples, evaluated using fungal culture and PAS stain, while group B comprised 93 patient samples evaluated using KOH, fungal culture and PAS. Diagnosis of onychomycosis was defined as clinical morphology plus at least one positive test result. RESULTS: In group A, sensitivities of fungal culture and PAS were 49.5% and 93.1% (P < 0.005), respectively. In group B, the most sensitive single test was PAS (88.2%) followed by KOH (55.9%) and fungal culture (29.4%). The combination of fungal culture and PAS (94.1%) was significantly (P < 0.001) more sensitive than that of KOH and culture (72.1%). CONCLUSION: PAS staining of nail clippings is much more sensitive than KOH and fungal culture for the diagnosis of onychomycosis. Based on our results, we propose a diagnostic algorithm for onychomycosis that takes into consideration the sensitivity, cost-effectiveness and necessary time for each test.

Ensiling Characteristics and the In situ Nutrient Degradability of a By-product Feed-based Silage.

This study was conducted to evaluate the ensiling characteristics and the in situ degradability of a by-product feed (BF)-based silage. Before ensilation, the BF-based mixture was composed of 50% spent mushroom substrate, 21% recycled poultry bedding, 15% ryegrass straw, 10.8% rice bran, 2% molasses, 0.6% bentonite, and 0.6% microbial inoculant on a wet basis and ensiled for up to 4 weeks. The BF-based silage contained on average 39.3% moisture, 13.4% crude protein (CP), and 52.2% neutral detergent fiber (NDF), 49% total digestible nutrient, and 37.8% physically effective NDF1.18 on a dry matter (DM) basis. Ensiling the BF-based silage for up to 4 weeks affected (p<0.01) the chemical composition to a small extent, increased (p<0.05) the lactic acid and NH3-N content, and decreased (p<0.05) both the total bacterial and lactic acid bacterial counts from 10(9) to 10(8) cfu/g when compared to that before ensiling. These parameters indicated that the silage was fermented and stored well during the 4-week ensiling period. Compared with rice or ryegrass straws, the BF-based silage had a higher (p<0.05) water-soluble and filterable fraction, a lower insoluble degradable DM and CP fraction (p<0.05), a lower digestible NDF (p<0.05) fraction, a higher (p<0.05) DM and CP disappearance and degradability rate, and a lower (p<0.05) NDF disappearance and degradability rate. These results indicated that cheap, good-quality BF-based roughage could be produced by ensiling SMS, RPB, rice bran, and a minimal amount of straw.

A randomized, 'head-to-head' pilot study comparing the effects of etanercept monotherapy vs. etanercept and narrowband ultraviolet B (NB-UVB) phototherapy in obese psoriasis patients.

BACKGROUND: Etanercept is a tumour necrosis factor-alpha antagonist used for the treatment of moderate-to-severe psoriasis. Current opinion suggests that etanercept may have reduced efficacy in obese patients. Narrowband ultraviolet B (NB-UVB) phototherapy is unaffected by body weight and the addition of NB-UVB to etanercept therapy may supplement the efficacy of etanercept in these patients. OBJECTIVE: To evaluate the efficacy and safety of NB-UVB phototherapy when administered in conjunction with 50 mg of etanercept once weekly in the treatment of obese patients with moderate-to-severe plaque psoriasis. METHODS: Thirty psoriasis patients with a body mass index (BMI) greater than 30 were enrolled into this randomized, 'head-to-head' comparison study. All subjects received 50 mg of etanercept twice weekly for 12 weeks and then randomized to receive either etanercept monotherapy or combination etanercept and NB-UVB three times weekly for an additional 12 weeks. Treatment response was evaluated using Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician's Global Assessment (PGA) scores. RESULTS: Twenty-five subjects completed the study. At 12 weeks, 48% of all patients achieved PASI 75. By Week 24, 62.5% of all patients achieved PASI 75. Patients in the etanercept monotherapy and combination etanercept and NB-UVB phototherapy arms had similar rates of achieving PASI 75 (46.7% vs. 53.3% of each group, respectively). CONCLUSION: Combination etanercept and NB-UVB has similar efficacy to etanercept monotherapy in obese patients. This result indicates that even in the setting of obesity, the majority of patients respond well to etanercept, with or without NB-UVB.

A review of monochromatic excimer light in vitiligo.

Phototherapy is a mainstay of vitiligo treatment and has varying rates of efficacy. Narrowband ultraviolet (UV) B (NB-UVB) and UVA have been used for decades, but it is only recently that monochromatic excimer light (MEL) was developed for use in dermatology and adapted for the treatment of vitiligo. The specific 308-nm radiation wavelength is delivered in a targeted form by the xenon-chloride excimer laser and is also available in an incoherent form that is commonly referred to as the excimer lamp. MEL administered by both laser and lamp has shown efficacy superior to NB-UVB for the treatment of vitiligo and induces more changes at the cellular level than conventional UVB modalities. The excimer laser is effective in adults and children with vitiligo in all skin types as monotherapy or in combination with other established vitiligo therapeutics. Treatment regimens studied included excimer laser two to three times weekly for up to 36 weeks. Patients commonly achieved > 75% repigmentation. The laser has also been used in combination with topical corticosteroids, calcineurin inhibitors and vitamin D analogues, as well as surgery, thus further expanding treatment options for patients with vitiligo. The excimer lamp has been used for treatments one to three times a week for up to 24 weeks and was found to be equal to excimer laser in a head-to-head comparison. It has also been used in combination with topical corticosteroids and oral vitamin E. Both MEL modalities have a limited adverse side-effect profile. Long-term effects are yet to be determined; however, based on available data on UVB phototherapy as well as the properties of MEL devices, there is probably only a minimal increased malignancy risk.

Molecular characterization of the human ABO blood group orthologus system in pigs.

The selection and use of animals with blood group 0 in the process of transplanting pig organs or tissues into humans can positively contribute to the control of acute immune rejection due to differences in blood groups. Exon-specific PCRs for the porcine blood group A transferase gene against genomic DNA from either blood group A or 0 animals resulted in the amplification failure of the A0 blood group gene exon 8 from blood group 0 animals. To characterize the genetic abnormality in the genome of blood group 0 animals, we screened bacterial artificial chromosome (BAC) clones from a Korean native pig BAC library which had the blood group 0 allele, and carried out shotgun sequencing. The analysis showed that the 0 allele has a large deletion between exon 7 of the A0 blood group gene and the neighbouring SURF6. We also showed that the ABO blood group antigens in humans and the A0 blood group antigens in pigs are coded by mutations within the orthologous glycosyltransferase gene. In addition, we developed a multiplex genotyping method for the porcine A0 blood group gene.

Comparative rapid onset of efficacy between doxazosin gastrointestinal therapeutic system and tamsulosin in patients with lower urinary tract symptoms from benign prostatic hyperplasia: a multicentre, prospective, randomised study.

AIMS: To compare the rapidity of improvement in lower urinary tract symptoms (LUTS) for the doxazosin gastrointestinal therapeutic system (GITS) and tamsulosin in benign prostatic hyperplasia (BPH) patients. METHODS: A total of 207 patients were randomised to one of two groups for a 12-week daily treatment with doxazosin-GITS 4 mg or tamsulosin 0.2 mg. The primary end-point was to compare the early onsets of efficacy between the two drugs. This was assessed by analysing the changes from baseline in the total International Prostate Symptom Score (IPSS) in the early period of treatment. Secondary aims were to compare improvements in obstructive/irritative subscore and quality of life (QoL) score between the two groups, and to evaluate the adverse events (AEs) with the drugs. RESULTS: After 12 weeks of treatment, both groups showed significant improvements in IPSS scores (total, obstructive and irritative subscores, QoL score) from baseline (p < 0.0001). However, the doxazosin-GITS group showed significantly greater improvements in total IPSS and obstructive subscore than the tamsulosin group in the early period (p < 0.05). Improvements in irritative subscore (within 4 weeks) and QoL score (during 12 weeks) were not significantly different between the groups. The incidences of AEs were similar between the groups. CONCLUSION: In this study, doxazosin-GITS showed significantly more rapid onset of efficacy and similar AEs compared with tamsulosin in BPH patients with LUTS. We believe this will probably improve patient compliance. Future studies with a larger number of patients and a longer follow-up period will be required to confirm this.

Transcriptional repression of PTEN in neural cells using CRISPR/dCas9 epigenetic editing.

After damage to the adult mammalian central nervous system (CNS), surviving neurons have limited capacity to regenerate and restore functional connectivity. Conditional genetic deletion of PTEN results in robust CNS axon regrowth, while PTEN repression with short hairpin RNA (shRNA) improves regeneration but to a lesser extent, likely due to suboptimal PTEN mRNA knockdown using this approach. Here we employed the CRISPR/dCas9 system to repress PTEN transcription in neural cells. We targeted the PTEN proximal promoter and 5' untranslated region with dCas9 fused to the repressor protein Krüppel-associated box (KRAB). dCas9-KRAB delivered in a lentiviral vector with one CRISPR guide RNA (gRNA) achieved potent and specific PTEN repression in human cell line models and neural cells derived from human iPSCs, and induced histone (H)3 methylation and deacetylation at the PTEN promoter. The dCas9-KRAB system outperformed a combination of four shRNAs targeting the PTEN transcript, a construct previously used in CNS injury models. The CRISPR system also worked more effectively than shRNAs for Pten repression in rat neural crest-derived PC-12 cells, and enhanced neurite outgrowth after nerve growth factor stimulation. PTEN silencing with CRISPR/dCas9 epigenetic editing may provide a new option for promoting axon regeneration and functional recovery after CNS trauma.

Correlation of maximum flexion with clinical outcome after total knee replacement in Asian patients.

This study aimed to determine the correlation between the amount of maximum flexion and the clinical outcome in 207 Koreans (333 knees) undergoing total knee replacement. The association of maximum flexion with clinical outcome was evaluated one year postoperatively using three scoring systems; the American Knee Society score, Western Ontario McMaster Universities Osteoarthritis index and the Short Form-36. The mean maximum flexion decreased post-operatively at 12 months from 140.1 degrees (60 degrees to 160 degrees ) to 133.0 degrees (105 degrees to 150 degrees ). Only the social function score of the Short Form-36 correlated significantly with maximum flexion (correlation coefficient = 0.180, p = 0.039). In comparative analyses of subgroups divided by a maximum flexion of 120 degrees , we found no significant differences in any parameters except the social function score of the Short Form-36 (41.9 vs 47.3, p = 0.031). Knees with a maximum flexion of more than 135 degrees had a better functional Western Ontario McMasters Universities Osteoarthritis index score than knees with maximum flexion of 135 degrees or less (17.5 vs 14.3, p = 0.031). We found only weak correlation between the postoperative maximum flexion and the clinical parameters for pain relief, function and quality of life, even in Korean patients. Efforts to increase post-operative maximum flexion should be exercised with caution until concerns relating to high-flexion activities are sufficiently resolved.

Systemic herpes simplex virus infection following cadaveric renal transplantation: a case report.

Herpes simplex virus (HSV) infection usually occurs in immunocompromised or severely debilitated patients. It is not so common in patients with renal transplants. The diagnosis can only be made histologically. It usually occurs during or shortly after treatment of graft rejection with high-dose steroids. We have recently experienced a case of HSV esophagitis and nephropathy in the renal allograft biopsy, which was identified by histology, immunostaining, and electron microscopy. A 43-year-old woman underwent cadaveric renal transplantation with cyclosporine and prednisolone treatment. Twelve months later, she developed renal insufficiency and proteinuria. Allograft renal biopsy showed some evidence of acute rejection. She was treated with 3 successive days of methylprednisolone (1.0 g/d) intravenously and continued tapering of steroids. Three weeks after steroid pulse therapy, she had throat pain, oral cavity ulcer, dysphagia, and febrile sensation. Esophagoscopy revealed multiple confluent ulcers in the whole esophagus, and biopsy showed enlarged epithelial cells with prominent nuclei. Immunohistochemically, the epithelial cells were positive with a monoclonal antibody to HSV type 1. She was started on acyclovir intravenously, which was continued for a week. After a week, her symptoms began to improve and repeat endoscopy showed no residual esophagitis. A renal allograft infection with HSV can persist in heavily immunosuppressed patients with recurrent rejection episodes. HSV mainly affects tubular cells causing necrosis, a major reason for functional deterioration. A biopsy is required for diagnosis.

Measuring the effect of femoral malrotation on knee joint biomechanics for total knee arthroplasty using computational simulation.

OBJECTIVES: Malrotation of the femoral component can result in post-operative complications in total knee arthroplasty (TKA), including patellar maltracking. Therefore, we used computational simulation to investigate the influence of femoral malrotation on contact stresses on the polyethylene (PE) insert and on the patellar button as well as on the forces on the collateral ligaments. MATERIALS AND METHODS: Validated finite element (FE) models, for internal and external malrotations from 0° to 10° with regard to the neutral position, were developed to evaluate the effect of malrotation on the femoral component in TKA. Femoral malrotation in TKA on the knee joint was simulated in walking stance-phase gait and squat loading conditions. RESULTS: Contact stress on the medial side of the PE insert increased with internal femoral malrotation and decreased with external femoral malrotation in both stance-phase gait and squat loading conditions. There was an opposite trend in the lateral side of the PE insert case. Contact stress on the patellar button increased with internal femoral malrotation and decreased with external femoral malrotation in both stance-phase gait and squat loading conditions. In particular, contact stress on the patellar button increased by 98% with internal malrotation of 10° in the squat loading condition. The force on the medial collateral ligament (MCL) and the lateral collateral ligament (LCL) increased with internal and external femoral malrotations, respectively. CONCLUSIONS: These findings provide support for orthopaedic surgeons to determine a more accurate femoral component alignment in order to reduce post-operative PE problems.Cite this article: K-T. Kang, Y-G. Koh, J. Son, O-R. Kwon, C. Baek, S. H. Jung, K. K. Park. Measuring the effect of femoral malrotation on knee joint biomechanics for total knee arthroplasty using computational simulation. Bone Joint Res 2016;5:552-559. DOI: 10.1302/2046-3758.511.BJR-2016-0107.R1.

Atherothrombotic middle cerebral artery territory infarction: topographic diversity with common occurrence of concomitant small cortical and subcortical infarcts.

BACKGROUND AND PURPOSE: MRI has superior capabilities for the detection of cerebral infarcts compared with CT. CT was used to locate infarcts in most previous studies of atherothrombotic middle cerebral artery (MCA) territory infarcts. Thus, there was a possibility of missing concomitant small infarcts. More accurate identification of topographic lesions in MCA territory with MRI may help to establish the pathogenesis of stroke. The present study determines topographic patterns, distribution of vascular lesions, and probable mechanisms. METHODS: Forty-two patients with MCA territory infarcts on routine MRI and no major cause of cardioembolism were studied with conventional angiography or MR angiography. RESULTS: The topographic patterns seen on MRI were subdivided into 4 groups: cortical border-zone infarcts (n=6), pial territory infarcts without insular infarct (n=3), pial territory infarcts with insular infarct (n=14), and large subcortical infarcts (n=19). Of 6 patients with cortical border-zone infarcts, 4 had concomitant small cortical or subcortical multiple lesions. Angiography showed intrinsic MCA disease in 4 patients. Of 3 patients with pial territory infarcts without insular infarct, 2 also had small multiple centrum ovale lesions. All had intrinsic MCA disease. Pial territory infarcts with partial or whole insular lesions were present in 10 and 4 patients, respectively. Five patients had additional multiple cortical or subcortical lesions. Ten patients had intrinsic MCA disease. Of the 19 patients with large subcortical infarcts, 12 had centrum ovale infarcts, and 4 had both basal ganglia and centrum ovale lesions. Ten had concomitant small cortical or subcortical lesions. Six patients had intrinsic MCA disease. CONCLUSIONS: Similar vascular lesions induce different topographic patterns in MCA territory infarction, which are related to individual vascular variability, degree of primary and secondary collateralization, and pathogenesis of infarcts. Our study indicates that concomitant small cortical or subcortical lesions are also commonly associated findings in diverse patterns of MCA territory infarction, which can mostly be explained by probable embolic mechanism.

Effect of protein kinase C inhibitor (PKCI) on radiation sensitivity and c-fos transcription.

PURPOSE: The human genetic disorder ataxia-telangiectasia (AT) is a multisystem disease characterized by extreme radiosensitivity. Although ionizing radiation was known to induce c-fos transcription and cellular protein kinase C (PKC) induces the expression of this immediate response gene, little is known about how mutated AT (ATM) or PKC-mediated signal transduction pathway modulates the c-fos gene transcription and gene expression. Here we have studied the effect of PKC inhibitor (PKCI) on radiation sensitivity and c-fos transcription in normal and AT cells, and also studied whether PKCI effect on c-fos occurs in Ras-dependent pathway. METHODS AND MATERIALS: Normal (LM217) and AT (AT5BIVA) cells were transfected with PKCI expression plasmid and integration and overexpression of PKCI was evaluated by polymerase chain reaction and northern blotting, respectively. Cells were irradiated at a dose of 5 Gy/min with 137Cs irradiator and harvested 48 h after irradiation and investigated apoptosis with TUNEL method. The c-fos transcription activity was studied by performing compute assisted tomography (CAT) assay of reporter gene after transfection of c-fos CAT plasmid into LM and AT cells. Overexpression of Ras protein in transfected cells was shown by western blotting. RESULTS: Our results demonstrated for the first time a role of PKCI on the radiation sensitivity and c-fos transcription in LM and AT cells. PKCI increased radiation induced apoptosis in LM cells (5% to 20%) but reduced apoptosis slightly in AT cells. The basal c-fos transcription activity is 70 times lower in AT cells than in LM cells. This c-fos transcription activity was repressed by overexpression of PKCI in LM cells but not in AT cells. After induction of c-fos by Ras protein, overexpression of PKCI repressed c-fos transcription in LM cells but not in AT cells. CONCLUSIONS: Overexpression of PKCI increased radiation sensitivity and repressed c-fos transcription in LM cells but not in AT cells, and this is related with Ras. These results suggest that the effect of PKCI on c-fos transcription activity is related with Ras dependent signal transduction pathways and these mechanisms are different between normal fibroblasts, LM and ATM mutated, AT cells. The data obtained by this study provided evidence for novel transcriptional difference between LM and AT cells and this may be a reason for increased radiation sensitivity of AT cells.

Radionuclide therapy of skin cancers and Bowen's disease using a specially designed skin patch.

UNLABELLED: Skin cancer is the most common malignancy in humans. Therapeutic modalities for skin cancer are local destruction, radiotherapy and surgery. External radiation therapy leads to good results, however, generally 5-6 wk of treatment is needed to deliver optimal radiation dose to tumors. In this study, a beta-emitting radionuclide, 166Ho, impregnated in a specially designed patch, was used on superficial skin cancers and Bowen's disease for local irradiation. METHODS: Ten mice with chemically induced skin tumors were studied. Five-millimeter size patches containing 22.2-72.15 MBq (0.6-1.95 mCi) 166Ho were applied to the tumor surface for 1-2 hr. In a human trial, patients with squamous-cell carcinoma (n = 3), basal cell carcinoma (n = 1) and Bowen's disease (n = 1) were treated with patches containing 273.8-999 MBq (7.4-27 mCi) of 166Ho for 30 min to 1 hr. Pathologic examination was performed 4-7 wk after treatment in an animal model. Skin biopsy was performed 8 wk post-treatment in four patients. RESULTS: Tumor destruction was seen 1 wk post-treatment, however, radiation dermatitis or ulceration developed at the site of radionuclide application. Those reactions healed gradually with fibrosis or epithelialization, which was confirmed pathologically. No significant adverse reaction to radiation except subcutaneous fibrosis was found. CONCLUSION: Superficial skin tumors could be successfully treated by topical application of beta-emitting radionuclides.

Effects of capsaicin on chemically-induced two-stage mouse skin carcinogenesis.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a principal pungent ingredient of hot red peppers. There are some controversies with regard to its inherent tumorigenicity and mutagenicity. The present work was undertaken to assess tumor initiating and promotional effects of capsaicin in a two-stage mouse skin carcinogenesis model. A single topical application of capsaicin (10 micromol) followed by twice-weekly applications of 12-O-tetradecanoylphorbol-13-acetate onto shaven backs of female ICR mice resulted in no significant increases in incidence and multiplicity of skin tumors, compared with the solvent-pretreated control animals. Repeated topical applications of capsaicin alone failed to promote 7,12-dimethylbenz[a]anthracene-initiated mouse skin tumorigenesis, but moderately inhibited the papilloma formation when given prior to each topical dose of phorbol ester.

Chemopreventive activity of chlorophyllin against mouse skin carcinogenesis by benzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide.

Chlorophyllin (CHL), the sodium and copper salt of chlorophyll, was tested for its chemopreventive activity against tumorigenesis induced by benzo[a]pyrene (B[a]P) and its ultimate electrophilic and carcinogenic metabolite, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide(BPDE). Administration of CHL (15 mg/kg body wt) by gavage to female ICR mice 30 min prior to a topical application of B[a]P or BPDE resulted in significant reduction in both incidence and multiplicity of skin tumors initiated by these carcinogens. CHL was rapidly distributed in the skin and other tissues of mice after oral administration. Taken together, these results suggest that CHL is a potential chemopreventive agent.

Chemoprotective properties of chlorophyllin against vinyl carbamate, p-nitrophenyl vinyl ether and their electrophilic epoxides.

Chlorophyllin (CHL), a water-soluble sodium and copper derivative of chlorophyll, has been shown to be a strong antimutagen in several test systems, but its mechanism of antimutagenic action is largely unknown. In the present study, we have found the protective properties of CHL against vinyl carbamate, p-nitrophenyl vinyl ether and their electrophilic epoxides. CHL exhibited dose-related inhibition of his+ reversion in Salmonella typhimurium TA 1535 induced by these mutagens. Formation of DNA adducts from vinyl carbamate epoxide (VCO) and 2'-(4-nitrophenoxy)oxirane (NPO) was also markedly attenuated in the presence of CHL. Oral administration of CHL prior to the topical application of each of the above carcinogens resulted in significant reduction in both incidence and multiplicity of skin tumors in mice. The effective protection by CHL against VCO and NPO suggest that its formation of inactive complexes with these carcinogens is mediated by mechanisms other than pi-pi interactions.

Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice.

A wide array of phytochemicals have been shown to possess potential cancer chemopreventive properties. Ginger contains pungent phenolic substances with pronounced antioxidative and antiinflammatory activities. In the present study, we have determined the antitumor promotional activity of [6]-gingerol, a major pungent principle of ginger, using a two-stage mouse skin carcinogenesis model. Topical application of [6]-gingerol onto shaven backs of female ICR mice prior to each topical dose of 12-O-tetradecanoylphorbol-13-acetate (TPA) significantly inhibited 7,12-dimethylbenz[a]anthracene-induced skin papillomagenesis. The compound also suppressed TPA-induced epidermal ornithine decarboxylase activity and inflammation.

Antioxidant and anti-tumor promoting activities of the methanol extract of heat-processed ginseng.

Heat treatment of Panax ginseng C.A. Meyer at a temperature higher than that applied to the conventional preparation of red ginseng yielded a mixture of saponins with potent antioxidative properties. Thus, the methanol extract of heat-processed neoginseng (designated as 'NGMe') attenuated lipid peroxidation in rat brain homogenates induced by ferric ion or ferric ion plus ascorbic acid. Furthermore, the extract protected against strand scission in phiX174 supercoiled DNA induced by UV photolysis of H2O2, and was also capable of scavenging superoxide generated by xanthine-xanthine oxidase or by 12-O-tetradecanoylphorbol-13-acetate (TPA) in differentiated human promyelocytic leukemia (HL-60) cells. Topical application of NGMe onto shaven backs of female ICR mice 10 min prior to TPA, significantly ameliorated skin papillomagenesis initiated by 7,12-dimethylbenz[a]anthracene. Moreover, TPA-induced enhancement of epidermal ornithine decarboxylase (ODC) activity and ODC mRNA expression was abolished by a topical dose (0.68 mg) of NGMe. Likewise, TPA-induced production of tumor necrosis factor- in mouse skin was inhibited by NGMe pretreatment.