National Library of Medicine

Pseudohypericin and hyperforin in Hypericum perforatum from Northern Turkey: variation among populations, plant parts and phenological stages.

J Integr Plant Biol. 2008 May;50(5):575-80

Authors: Cirak C, Radusiene J, Janulis V, Ivanauskas L

Hypericum perforatum is a perennial medicinal plant known as "St. John's wort" in Western Europe and has been used in the treatment of several diseases for centuries. In the present study, morphologic, phenologic and population variability in pseudohypericin and hyperforin concentrations among H. perforatum populations from Northern Turkey was investigated for the first time. The aerial parts of H. perforatum plants representing a total of 30 individuals were collected at full flowering from 10 sites of Northern Turkey to search the regional variation in the secondary metabolite concentrations. For morphologic and phenologic sampling, plants from one site were gathered in five phenological stages: vegetative, floral budding, full flowering, fresh fruiting and mature fruiting. The plant materials were air-dried at room temperature and subsequently assayed for chemical concentrations by high performance liquid chromatography. Secondary metabolite concentrations ranged from traces to 2.94 mg/g dry weight (DW) for pseudohypericin and traces -6.29 mg/g DW for hyperforin. The differences in the secondary metabolite concentrations among populations of H. perforatum were found to be significant. The populations varied greatly in hyperforin concentrations, whereas they produced a similar amount of pseudohypericin. Concentrations of both secondary metabolites in all tissues increased with advancing of plant development and higher accumulation levels were reached at flowering. Among different tissues, full opened flowers were found to be superior to stems, leaves and the other reproductive parts with regard to pseudohypericin and hyperforin accumulations. The present findings might be useful to optimize the processing methodology of wild-harvested plant material and obtain increased concentrations of these secondary metabolites.

PMID: 18713425 [PubMed - in process]

Successful treatment of spondylolisthesis with medicinal herbs.

Geriatr Gerontol Int. 2008 Jun;8(2):126-9

Authors: Tsuji K, Koizumi H, Okabe T

It has been reported that some herbal medicines may be effective for acute episodes of chronic nonspecific lower back pain. Spondylolisthesis is one of the causes of lower back or neck pain. To our knowledge, successful treatment of symptomatic spondylolisthesis with medicinal herbs has not been previously reported in the published work. A 63-year-old female had suffered from back pain for 4 years. Radiographs revealed spondylolisthesis at the L3 level. In another case, an 82-year-old female suffered from neck pain. X-ray examinations revealed cervical spondylolisthesis at the C4 level. Several herbs were administered to these patients with symptomatic spondylolisthesis according to the guidelines for herbal medicine. Significant improvements in pain were obtained within 4 weeks in both patients. The pain completely disappeared after 20 weeks (case 1) and 6 weeks (case 2) of treatment. Although surgical treatment is often performed for symptomatic spondylolisthesis, the findings of the present cases imply the therapeutic potential of herbal medicine in selected patients.

PMID: 18713165 [PubMed - in process]

Identification and characterization of active compounds and their metabolites by high-performance liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry after oral administration of a herbal extract of Epimedium koreanum Nakai to rats.

Rapid Commun Mass Spectrom. 2008 Aug 19;22(18):2813-2824

Authors: Wu C, Sheng Y, Zhang Y, Zhang J, Guo B

Epimedium is an important traditional Chinese medicine that is widely used throughout China as a tonic, aphrodisiac, and antirheumatic medicine. Flavonoids are considered to be the active compounds in Epimedium. In the study reported here, high-performance liquid chromatography coupled with Fourier transform-ion cyclotron resonance mass spectrometry (HPLC/FTICR-MS) was developed to identify active compounds and their metabolites after oral administration of a herbal extract of Epimedium koreanum Nakai to rats, using parent mass list triggered data-dependent multiple-stage accurate mass analysis at a resolving power of 100 000 in the external calibration mode. Nine flavonoids were identified in rats. The chemical formulae with unsaturation numbers calculated from accurate m/z values of precursor and product ions were used to assign the structures of metabolites and the chemical sites of metabolism. The mass accuracies obtained for all full-scan MS and MS(n) spectra were within 3 ppm (<1 ppm in most cases). The majority of the metabolites identified have been previously reported, but three compounds were noted for the first time in rats. By contrasting the analytical results obtained from the herbal extract with those obtained from biological specimens, the profile of flavonoid biotransformation in Epimedium was obtained and the metabolic pathways of these components, in rats, are described. The results should be of use in targeting potential active ingredients in Epimedium. Copyright (c) 2008 John Wiley & Sons, Ltd.

PMID: 18712702 [PubMed - as supplied by publisher]

Complementary and alternative therapies among very long-term breast cancer survivors.

Breast Cancer Res Treat. 2008 Aug 20;

Authors: Carpenter CL, Ganz PA, Bernstein L

Breast cancer patients may have different complementary and alternative medicine (CAM) usage rates and may turn to CAM for different reasons than healthy adults. CAM has mostly been studied in recently diagnosed women; no studies have included survivors 10 years post-diagnosis. We examined very long-term breast cancer survivors to determine whether CAM users had dissimilar patterns of association with survivorship factors. Interviews of 374 breast cancer case patients from a population-based case-control breast cancer study of young women from Los Angeles County, California, during the 1980s occurred at follow-up; 371 patients with complete information were included. CAM represented 28 herbal remedies. Quality-of-life originated from the Medical Outcomes Study Short Form 36 questionnaire (SF-36). Higher rates of CAM (59%) usage occurred compared to nationwide estimates. CAM users resembled non-users on follow-up age, exercise, original disease, treatment, smoking, body-mass index, alcohol, and fear of recurrence. CAM users had a higher prevalence of medical co-morbidities (P = 0.0005), and scored significantly lower on the SF-36 emotional well-being subscale than non-CAM users (P = 0.01). CAM users and non-users did not differ on the SF-36 physical sub-scale. Very long-term breast cancer survivors who use CAM may have poorer emotional functioning and more medical problems than non-users.

PMID: 18712472 [PubMed - as supplied by publisher]

[Tolerability and efficacy of a herbal combination preparation in children and adolescents with recurrent infections of the upper respiratory tract]

MMW Fortschr Med. 2008 Jun 26;150 Suppl 2:85-90

Authors: Berger T

PMID: 18712128 [PubMed - in process]

The invitro assessment of antibacterial effect of papaya seed extract against bacterial pathogens isolated from urine, wound and stool.

Ethiop Med J. 2008 Jan;46(1):71-7

Authors: Yismaw G, Tessema B, Mulu A, Tiruneh M

BACKGROUND: Carica papaya family Caricaceacae is one of the herbal remedies, which has recently become a subject of research focus. It is used in traditional medicine for variety of purposes in treating infectious and noninfectious diseases. OBJECTIVE: The objective of this study was to assess the antibacterial effect of papaya seed extract against bacterial pathogens isolated from wound, urine and stool. METHODS: This analytical experimental study was conducted in Jimma University, School of Medical Laboratory Technology, Microbiology laboratory between February to March 2005. The antibacterial activity of methanol extract of papaya seed was investigated against specific pathogenic bacteria isolated from wound, urine and stool by an agar dilution technique and the crude preparation was assessed by an agar diffusion technique. The growth or inhibition of control strains of Escherichia coli, Staphylococcus aureus, Salmonella typhi, and Pseudomonas aeruginosa as well as the clinical isolates of these bacteria were determined in growth media. RESULTS: Results obtained in this study indicate that the minimum inhibitory concentration of papaya seed extract for 50% of the test bacteria was 18.38mg/ml and for S. typhi the MIC was at 11.8 mg/ml of extract. However, the growth inhibitory effect of papaya seed extract was not observed for P. aeruginosa up to 26.25 mg /ml of extract. Even though, the minimum bactericidal concentration is higher than the minimum inhibitory concentration of papaya seed extract (13.13 mg/ml, 11.8 mg/ml respectively) against S. typhi control and clinical isolates, the minimum bactericidal concentration for 50% of the tested bacteria was found to be similar with the minimum inhibitory concentration of the test bacteria, CONCLUSION: Papaya seed could be used as an effective antibacterial agent for the tested organisms. Nevertheless, preclinical studies including invivo animal models and clinical trial on the effect of the seed are essential before advocating large-scale therapy.

PMID: 18711992 [PubMed - in process]

Vitamin supplement use among children with Down's syndrome and risk of leukaemia: a Children's Oncology Group (COG) study.

Paediatr Perinat Epidemiol. 2008 May;22(3):288-95

Authors: Blair CK, Roesler M, Xie Y, Gamis AS, Olshan AF, Heerema NA, Robison LL, Ross JA,

Vitamin supplements have been proposed for children with Down's syndrome (DS) with claims of improving cognitive abilities, or immune or thyroid function. Several studies have shown decreased levels of zinc in this population. Because children with DS have a 50-fold increased risk of developing acute leukaemia during the first 5 years of life, we explored the relation between child vitamin and herbal supplement use and the risk of leukaemia in a case-control study. During the period 1997-2002, we enrolled 158 children with DS aged 0-18 years that were diagnosed with acute lymphoblastic leukaemia (ALL) (n = 97) or acute myeloid leukaemia (AML) (n = 61) at participating Children's Oncology Group institutions. We enrolled 173 DS children without leukaemia (controls), selected from the cases' primary care clinic and frequency-matched on age. Data were collected via telephone interviews with mothers of the index child regarding use of multivitamins, zinc, vitamin C, iron and herbal supplements, including age at first use, frequency and duration. Among controls, 57% reported regular multivitamin use (>/=3 times/week for >/=3 months) compared with 48% of ALL cases and 61% of AML cases. We found no evidence of an association between children's regular multivitamin use and ALL or AML (adjusted odds ratios [OR] = 0.94 [95% CI 0.52, 1.70] and 1.90 [0.73, 4.91] respectively). There was a suggestion of an increased risk for AML associated with regular multivitamin use during the first year of life or for an extended duration (ORs = 2.38 [0.94, 5.76] and 2.59 [1.02, 6.59] respectively). Despite being the largest study of DS-leukaemia, our sample size was small, resulting in imprecise effect estimates. Future research should include larger sample sizes as well as a full assessment of diet including vitamin supplementation to adequately examine the relation between nutritional status and childhood leukaemia.

PMID: 18426524 [PubMed - indexed for MEDLINE]

Factors influencing collagen biosynthesis.

J Cell Biochem. 2008 Jul 1;104(4):1150-60

Authors: Kavitha O, Thampan RV

The importance of collagen, the major structural protein of animal kingdom, in maintaining the normal structure and function of the skin is well known. The same property is exploited widely in medical and industrial fields in finding agents, which could influence the synthesis of this protein. In this context in vitro production of collagen is of high significance. A literature survey has been made to analyze the various factors that influence collagen biosynthesis. There are various physical and biological factors that can either induce or inhibit collagen biosynthesis at various levels of gene expression. However reports concentrating on the effects of plants-derived compounds in stimulating collagen synthesis are scanty. Since extracts of many plants are known to be beneficial in the wound healing process, plants-derived compounds will have a definite role in the regulation of collagen synthesis. The present study emphasizes the need for unearthing the role of these plant derived factors on collagen synthesis which will be of immense application in the medical field.

PMID: 18404678 [PubMed - indexed for MEDLINE]

Topical Polyphenon E in the treatment of external genital and perianal warts: a randomized controlled trial.

Br J Dermatol. 2008 Jun;158(6):1329-38

Authors: Stockfleth E, Beti H, Orasan R, Grigorian F, Mescheder A, Tawfik H, Thielert C

BACKGROUND: Benign external genital and perianal warts (condylomata acuminata) are disfiguring, displeasing skin tumours caused by human papillomavirus that may vitally burden affected patients and their partners. Current treatment options are still unsatisfactory due to low efficacy, high recurrence rates or an unfavourable side-effect profile. Although most recently prophylactic vaccines have been recommended for adolescent women, appropriate treatment modalities for anogenital warts are still needed. Green tea catechins exert antiviral, antioxidative, antiproliferative and immunostimulatory activity. Polyphenon E (MediGene AG, Munich, Germany), a proprietary extract of green tea leaves, was therefore investigated for the topical treatment of this frequent viral disease. OBJECTIVES: To investigate Polyphenon E 15% and 10% ointment for efficacy and safety in the treatment of anogenital warts in immunocompetent men and women. METHODS: Five hundred and three patients were randomized to receive either Polyphenon E 15% or 10% ointment or matching vehicle. The topical treatment was self-applied by the patients three times daily to all warts. Assessment of response and of adverse events was performed biweekly until complete clearance of all (baseline and new) anogenital warts or for up to 16 weeks. Recurrence was evaluated during a 12-week treatment-free follow-up period for patients with complete clearance. RESULTS: About 53% of patients treated with Polyphenon E 15% ointment showed complete clearance of all baseline and new anogenital warts, 51% for Polyphenon E 10% ointment, and 37% for vehicle (P = 0.01 and P = 0.03, respectively; two-sided Fisher's exact test; intent-to-treat population, last observation carried forward analysis). Women responded better than men, with about 60% of women and 45% of men in both active groups achieving complete clearance of all warts. Time to complete clearance was comparable for both strengths of Polyphenon E ointment. About 78% of all patients treated with either Polyphenon E 15% or 10% ointment showed wart clearance rates of 50% or better. Less than 6% and 4% of patients in the Polyphenon E 15% and 10% ointment groups experienced wart recurrence during follow-up. Polyphenon E ointments demonstrated a good safety profile with the majority of all adverse events being local application site reactions assessed as mild or moderate. Local reactions declined during continued treatment. CONCLUSIONS: The results indicate that Polyphenon E ointment is an efficacious and safe patient-applied topical treatment for external genital and perianal warts. Its use in intra-anal, intravaginal and cervical condylomas and other intraepithelial lesions warrants further clinical investigation.

PMID: 18363746 [PubMed - indexed for MEDLINE]

Gene expression profiling of macrophages following mice treatment with an immunomodulator medication.

J Cell Biochem. 2008 Jul 1;104(4):1364-77

Authors: de Oliveira CC, de Oliveira SM, Goes VM, Probst CM, Krieger MA, Buchi Dde F

Canova (CA) is a complex homeopathic medication used in diseases where the immune system is depressed. Previous studies demonstrated that it is neither toxic nor mutagenic and activates macrophages. We now evaluate CA effects on cytokine production and gene expression from mice macrophages. The global view of changes in expression of genes with known functions can provide a vivid picture of the way in which cell adapts to a changing environment or a challenge. We found a decrease in IL-2 and IL-4 production and a differential expression in 147 genes from CA group. These genes are mainly involved in transcription/translation, cell structure and dynamics, immune response, cytoprotection, enzymatic process, and receptors/ligands. With gene expression analysis we state that this medication provokes a reaction that involves alterations in gene expression profile mainly in the ones involved with macrophages activation, corroborating the laboratorial research and the clinical data.

PMID: 18286468 [PubMed - indexed for MEDLINE]

[Gastroprotective properties of phytomedicine tiol]

Georgian Med News. 2007 Oct;(151):65-7

Authors: Khvedelidze V, Baratashvili N, Niguriani N, Gabidzashvili M, Tsibadze L

Phitopreparation tiol is offered (5% fatty solution of Tea Leaf lipid complex) as a medicine. To determine gastroprotective effect of tiol generally accepted models of acute gastric ulcer were used: bitadion, atopanove and reserprinove stomach damages. An experiment was conducted on half-matured white mice weighting 140-160 g., which fast 24 hours before the experiment (only water was freely given to them). Animals were killed by immediate decapitation under light ether narcosis. Their stomachs were dissected along greater curvature of stomach and number of injuries were counted. The injuries were subdivided into hemorrhage, erosion and ulcer. Paul's "ulcer index" was calculated for any kind of damage. Each group consisted of 5 mice. Distilled water was used as control and aekol - to collate the gastroprotective effect. Results of the experiment showed that gastroprotective effect of tiol is greater than that of aekol's.

PMID: 18071217 [PubMed - indexed for MEDLINE]

Systemic inflammatory responses in patients with acute otitis media and the impact of treatment with sinupret.

Georgian Med News. 2007 Oct;(151):40-4

Authors: Chkhaidze I, Nemsadze K, Gotsadze K, Nikoleishvili E, Gordeladze G

The systemic inflammatory responses and the impact of sinupret therapy have been investigated in 14 patients with acute otitis media, AOM. The age of inspected individuals covered a range of 29.0+/-12.3 years. The blood samples were taken at the admission and after ten days treatment with sinupret. The dosage of sinupret application was two tablets or 50 drops three times per day. Utilizing the technique of enzymelinked immunoassays, the concentrations of two cytokines, TNF-alpha and IL-6, were measured in the blood serum. The minimum detectable amount of cytokines was less then 2.5 pg/ml. Age-matched five healthy subjects without significant medical history served for controls. The study proved an existence of systemic inflammatory responses under the AOM. In AOM patients as compared with healthy individuals the concentrations of both cytokines were elevated, although the difference reached the statistically significant level with respect to TNF-alpha but not to IL-6. After treatment with sinupret, the TNF-alpha level dropped noticeably, proving a recovery from the pathology. IL-6 displayed a similar pattern, although the difference between pre- and post-treatment samples was statistically nonsignificant. Assessment of varies cytokines and proper establishment of their profiles could detect more specific marker(s) of AOM of both bacterial or viral etiology and could promote thus a precise prediction of the outcome of the pathology. Generally, the estimation of cytokines under AOM could offer a powerful tool for the objective evaluation of efficacy of treatment and for the avoidance of the ineffective drug therapy.

PMID: 18071211 [PubMed - indexed for MEDLINE]

[Complex treatment of mastopathy patients with concomitant diseases]

Georgian Med News. 2007 Oct;(151):33-7

Authors: Katashvili Z, Nemsadze G, Gvamichava P, Vekua N, Nemsadze D

Efficiency value of complex treatment of patients with cystic disease during side-illnesses. The aim of the article was to study the efficiency of complex treatment of mastopitia patients with concomitant diseases. The complex therapy of 1044 patients was carried out. Patients with cystic disease who does not suffer concomitant diseases (152 patients) where treated with mastodinon, vitamins, ginsheng, dehidratation, trancvilizators, antihistamines, drugs of K. After 24-26 months of treatment 144 (95%) patients fully recovered. The subjective progress was found in 8 cases (4%). In group with hormonal disorders recovery was in 120 cases (90%) and the subjective progress was in 13 patients (6%). Apart, the hormonal drugs had been used considering hormonal profile. 401 patients with concomitant diseases of genitals were treated with hormones, iodinotherapy and mastodinon. The best result in this group has been shown in patients with uterus fibromiomas - 110 patients and with ovarian micro cists with no need of surgical treatment - 78 patients compared with chronic adneqsitis (213 patients) - 90 (82%) patients; 67 (86%) patients; 162 (76%) patients. In case of concomitant diseases of liver and gold bladder, the treatment was effective in 113 (89%) patients. Ineffective treatment has been discovered in 5% 6 (5%) patients with hepatopathia and 28 (22%) patients with cholecistitis. The L-thyroxin was included in treatment in case of hypothyreosis (66 patients). Positive effect has been reached in 52 (78,5%) patients and progressive recovery was found in 13 (20%) patients. The complex therapy was effective for 648 (62%) of 1044 patients. Positive development was in 238 (27,8%) cases. In the group of patients who did not suffer concomitant diseases 4,9% has shown progress in treatment and 92,6% fully recovered.

PMID: 18071209 [PubMed - indexed for MEDLINE]

Case-control study of coffee consumption and the risk of endometrial endometrioid adenocarcinoma.

Eur J Cancer Prev. 2008 Aug;17(4):358-63

Authors: Koizumi T, Nakaya N, Okamura C, Sato Y, Shimazu T, Nagase S, Niikura H, Kuriyama S, Tase T, Ito K, Tsubono Y, Okamura K, Yaegashi N, Tsuji I

This study examined the association between coffee consumption and the risk of endometrial endometrioid adenocarcinoma (EEA) in Japan by a case-control design. The cases consisted of 107 women less than 80 years of age from two medical centers who had been histopathologically diagnosed to have EEA. The controls, selected from the participants of a cancer-screening program, were 214 women, with two controls selected for each case (matched for age and for area of residence). A self-administered questionnaire containing questions to determine dietary and beverage consumption, as well as reproductive history, was distributed to the cases and controls. Conditional logistic regression analysis was used to estimate the odds ratio (OR) of EEA for three levels of coffee consumption with adjustment for potential confounding factors. The multivariate-adjusted OR of EEA for individuals in the highest tertile of coffee consumption (2 to 3 cups or more/day) was 0.4 [95% confidence interval (CI), 0.2-0.9], and that of cases in the intermediate tertile (5 to 6 times/week-1 cup/day) was 0.6 (95% CI, 0.3-1.2), relative to the individuals in the lowest tertile of coffee consumption (3 to 4 times or less/week) (P for trend=0.014). The above association was observed in postmenopausal women (P for trend=0.016), but not in premenopausal women (P for trend=0.90). This study thus revealed an inverse dose-response relationship between coffee consumption and the risk of EEA, and its strong association in postmenopausal women but not in premenopausal women.

PMID: 18562962 [PubMed - indexed for MEDLINE]

Effects of dietary supplementation with the green tea polyphenol epigallocatechin-3-gallate on insulin resistance and associated metabolic risk factors: randomized controlled trial.

Br J Nutr. 2008 Aug 19;:1-9

Authors: Brown AL, Lane J, Coverly J, Stocks J, Jackson S, Stephen A, Bluck L, Coward A, Hendrickx H

Animal evidence indicates that green tea may modulate insulin sensitivity, with epigallocatechin-3-gallate (EGCG) proposed as a likely health-promoting component. The purpose of this study was to investigate the effect of dietary supplementation with EGCG on insulin resistance and associated metabolic risk factors in man. Overweight or obese male subjects, aged 40-65 years, were randomly assigned to take 400 mg capsules of EGCG (n 46) or the placebo lactose (n 42), twice daily for 8 weeks. Oral glucose tolerance testing and measurement of metabolic risk factors (BMI, waist circumference, percentage body fat, blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG) was conducted pre- and post-intervention. Mood was evaluated weekly using the University of Wales Institute of Science and Technology mood adjective checklist. EGCG treatment had no effect on insulin sensitivity, insulin secretion or glucose tolerance but did reduce diastolic blood pressure (mean change: placebo - 0.058 (se 0.75) mmHg; EGCG - 2.68 (se 0.72) mmHg; P = 0.014). No significant change in the other metabolic risk factors was observed. The EGCG group also reported feeling in a more positive mood than the placebo group across the intervention period (mean score for hedonic tone: EGCG, 29.11 (se 0.44); placebo, 27.84 (se 0.46); P = 0.048). In conclusion, regular intake of EGCG had no effect on insulin resistance but did result in a modest reduction in diastolic blood pressure. This antihypertensive effect may contribute to some of the cardiovascular benefits associated with habitual green tea consumption. EGCG treatment also had a positive effect on mood. Further studies are needed to confirm the findings and investigate their mechanistic basis.

PMID: 18710606 [PubMed - as supplied by publisher]

Coffee consumption and risk of endometrial cancer: A prospective study in Japan.

Int J Cancer. 2008 Aug 18;

Authors: Shimazu T, Inoue M, Sasazuki S, Iwasaki M, Kurahashi N, Yamaji T, Tsugane S,

Coffee has been proposed to decrease the circulating insulin and estrogen levels, which are related to the development of endometrial cancer. However, few studies have prospectively assessed the association between coffee consumption and endometrial cancer. We conducted a population-based prospective cohort study in 53,724 Japanese women aged 40-69 years with no history of cancer at baseline in 1990-1994. We used Cox proportional hazards regression analysis to estimate the hazard ratio (HR) and 95% confidence interval (CI) of endometrial cancer incidence in relation to coffee consumption. All reported p values are 2-tailed. During the 15-year follow-up period, we documented 117 cases of endometrial cancer. Coffee consumption was significantly associated with a decreased risk of endometrial cancer. After adjustment for age, study area, body mass index, menopausal status, age at menopause for postmenopausal women, parity, use of exogenous female hormones, smoking status and by consumption of green vegetables, beef, pork and green tea, the multivariate HRs (95% CI) of endometrial cancer in women who drank coffee </=2 days/week, 3-4 days/week, 1-2 cups/day and >/=3 cups/day were 1.00, 0.97 (0.56-1.68), 0.61 (0.39-0.97) and 0.38 (0.16-0.91), respectively (p for trend = 0.007). In contrast, green tea consumption was not significantly associated with a reduced risk of endometrial cancer (p for trend = 0.22). The inverse association between coffee consumption and risk of endometrial cancer was consistently observed in subgroup analyses stratified by potential confounders. Coffee consumption may be associated with a decreased risk of endometrial cancer. (c) 2008 Wiley-Liss, Inc.

PMID: 18711700 [PubMed - as supplied by publisher]

Topical application of a bioadhesive black raspberry gel modulates gene expression and reduces cyclooxygenase 2 protein in human premalignant oral lesions.

Cancer Res. 2008 Jun 15;68(12):4945-57

Authors: Mallery SR, Zwick JC, Pei P, Tong M, Larsen PE, Shumway BS, Lu B, Fields HW, Mumper RJ, Stoner GD

Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation.

PMID: 18559542 [PubMed - indexed for MEDLINE]

Clinical and Analytical Toxicology of Dietary Supplements: A Case Study and a Review of the Literature.

Biol Trace Elem Res. 2008 Aug 16;

Authors: van der Voet GB, Sarafanov A, Todorov TI, Centeno JA, Jonas WB, Ives JA, Mullick FG

The use of dietary supplements has grown dramatically in the last decade. A large number of dietary and herbal supplements escape regulatory and quality control; components of these preparations are poisonous and may contain, among other toxins, heavy metals. Uncontrolled use of dietary and herbal supplements by special populations, such as the military, may therefore pose a health risk. Clinical symptoms are not always properly attributed to dietary supplements; patients often do not mention supplement use to their health care provider. Therefore, a health risk estimate is hard to make on either the individual or the population level. The literature on this issue was reviewed and discussed in the light of a representative clinical-chemical case study. This case study was performed on a host of preparations that were used by one single individual in the military. Both essential (chromium, copper, zinc, and iron) and poisonous (arsenic, lead, and nickel) trace elements were determined using inductively coupled plasma combined with optical emission spectrometry (ICP-OES) or with mass spectrometry (ICP-MS). Arsenic and lead were detected at exposure levels associated with health risks. These health risks were detected predominantly in hormone-containing supplements and the herbs and botanicals used for performance enhancement. To the extent that this is a representative sample, there is an underestimation of supplement use and supplement risk in the US military, if not in the general population. Since clinical symptoms may be attributed to other causes and, unless patients are specifically asked, health care providers may not be aware of their patients' use of dietary supplements, a strong support of laboratory diagnostics, such as a toxicological screening of blood or urine, is required. In addition, screening of the preparations themselves may be advised.

PMID: 18709338 [PubMed - as supplied by publisher]

Chromium and polyphenols from cinnamon improve insulin sensitivity.

Proc Nutr Soc. 2008 Feb;67(1):48-53

Authors: Anderson RA

Naturally-occurring compounds that have been shown to improve insulin sensitivity include Cr and polyphenols found in cinnamon (Cinnamomon cassia). These compounds also have similar effects on insulin signalling and glucose control. The signs of Cr deficiency are similar to those for the metabolic syndrome and supplemental Cr has been shown to improve all these signs in human subjects. In a double-blind placebo-controlled study it has been demonstrated that glucose, insulin, cholesterol and HbA1c are all improved in patients with type 2 diabetes following Cr supplementation. It has also been shown that cinnamon polyphenols improve insulin sensitivity in in vitro, animal and human studies. Cinnamon reduces mean fasting serum glucose (18-29%), TAG (23-30%), total cholesterol (12-26%) and LDL-cholesterol (7-27%) in subjects with type 2 diabetes after 40 d of daily consumption of 1-6 g cinnamon. Subjects with the metabolic syndrome who consume an aqueous extract of cinnamon have been shown to have improved fasting blood glucose, systolic blood pressure, percentage body fat and increased lean body mass compared with the placebo group. Studies utilizing an aqueous extract of cinnamon, high in type A polyphenols, have also demonstrated improvements in fasting glucose, glucose tolerance and insulin sensitivity in women with insulin resistance associated with the polycystic ovary syndrome. For both supplemental Cr and cinnamon not all studies have reported beneficial effects and the responses are related to the duration of the study, form of Cr or cinnamon used and the extent of obesity and glucose intolerance of the subjects.

PMID: 18234131 [PubMed - indexed for MEDLINE]

(-)-Epigallocatechin gallate, a major constituent of green tea, poisons human type II topoisomerases.

Chem Res Toxicol. 2008 Apr;21(4):936-43

Authors: Bandele OJ, Osheroff N

(-)-Epigallocatechin gallate (EGCG) is the most abundant and biologically active polyphenol in green tea, and many of the therapeutic benefits of the beverage have been attributed to this compound. High concentrations of EGCG are cytotoxic and trigger genotoxic events in mammalian cells. Although this catechin affects a number of cellular systems, the genotoxic effects of several bioflavonoid-based dietary polyphenols are believed to be mediated, at least in part, by their actions on topoisomerase II. Therefore, the effects of green tea extract and EGCG on DNA cleavage mediated by human topoisomerase IIalpha and beta were characterized. The extract and EGCG increased levels of DNA strand breaks generated by both enzyme isoforms. However, EGCG acted by a mechanism that was distinctly different from those of genistein, a dietary polyphenol, and etoposide, a widely prescribed anticancer drug. In contrast to these agents, EGCG exhibited all of the characteristics of a redox-dependent topoisomerase II poison that acts by covalently adducting to the enzyme. First, EGCG stimulated DNA scission mediated by both isoforms primarily at sites that were cleaved in the absence of compounds. Second, exposure of EGCG to the reducing agent dithiothreitol (DTT) prior to its addition to DNA cleavage assays abrogated the effects of the catechin on DNA scission. Third, once EGCG stimulated topoisomerase II-mediated DNA cleavage, exposure to DTT did not effect levels of DNA strand breaks. Finally, EGCG inhibited the DNA cleavage activities of topoisomerase IIalpha and beta when incubated with either enzyme prior to the addition of DNA. Taken together, these results provide strong evidence that EGCG is a redox-dependent topoisomerase II poison and utilizes a mechanism similar to that of 1,4-benzoquinone.

PMID: 18293940 [PubMed - indexed for MEDLINE]