Hormone Therapy and Other Treatments for Symptoms of Menopause.

The results of large clinical trials have led physicians and patients to question the safety of hormone therapy for menopause. In the past, physicians prescribed hormone therapy to improve overall health and prevent cardiac disease, as well as for symptoms of menopause. Combined estrogen/progestogen therapy, but not estrogen alone, increases the risk of breast cancer when used for more than three to five years. Therefore, in women with a uterus, it is recommended that physicians prescribe combination therapy only to treat menopausal symptoms such as vasomotor symptoms (hot flashes) and vaginal atrophy, using the smallest effective dosage for the shortest possible duration. Although estrogen is the most effective treatment for hot flashes, nonhormonal alternatives such as low-dose paroxetine, venlafaxine, and gabapentin are effective alternatives. Women with a uterus who are using estrogen should also take a progestogen to reduce the risk of endometrial cancer. Women who cannot tolerate adverse effects of progestogens may benefit from a combined formulation of estrogen and the selective estrogen receptor modulator bazedoxifene. There is no highquality, consistent evidence that yoga, paced respiration, acupuncture, exercise, stress reduction, relaxation therapy, and alternative therapies such as black cohosh, botanical products, omega-3 fatty acid supplements, and dietary Chinese herbs benefit patients more than placebo. One systematic review suggests modest improvement in hot flashes and vaginal dryness with soy products, and small studies suggest that clinical hypnosis significantly reduces hot flashes. Patients with genitourinary syndrome of menopause may benefit from vaginal estrogen, nonhormonal vaginal moisturizers, or ospemifene (the only nonhormonal treatment approved by the U.S. Food and Drug Administration for dyspareunia due to menopausal atrophy). The decision to use hormone therapy depends on clinical presentation, a thorough evaluation of the risks and benefits, and an informed discussion with the patient.

Effects of dietary vitamin E concentration and source on sow, milk, and pig concentrations of α-tocopherol.

A total of 126 gilts and sows (PIC 1050) and their litters were used to determine the effects of dietary vitamin E concentration and source on sow plasma, milk, and pig concentrations of α-tocopherol. Additionally, we estimated the bioavailability of D-α-tocopheryl acetate (D-α-TAc) relative to DL-α-tocopheryl acetate (DL-α-TAc) when fed in diets containing dried distillers grains with solubles (DDGS). The 6 dietary treatments included DL-α-TAc at 44 and 66 mg/kg and D-α-TAc at 11, 22, 33, and 44 mg/kg. From breeding to d 69 of gestation, sows were fed 2.0 kg/d of a diet containing 40% DDGS, 0.30 mg/kg added Se, and no added vitamin E. Vitamin E treatments were fed from d 70 of gestation through weaning. Plasma was collected from sows on d 69 and 100 of gestation, at farrowing, and at weaning. Colostrum and milk samples were also collected. Plasma from 3 pigs per litter and heart and liver samples from 1 pig per litter were collected at weaning. Plasma, milk, and tissues from 6 litters per treatment were analyzed for α-tocopherol. Although tissue, plasma, and milk concentrations of α-tocopherol were the primary response criteria of interest, sow and litter performance were measured. As expected, treatment effects were not observed for lactation feed intake, sow BW, or backfat measurements. A trend (P = 0.085) for a treatment effect on average pig BW at weaning was detected, with pigs nursing sows fed 44 mg/kg DL-α-TAc weighing less because of a younger weaning age. No other differences in litter performance were observed. As D-α-TAc increased in the diet, sow plasma, colostrum, and milk, pig plasma, and pig heart concentrations of α-tocopherol increased (linear, P < 0.03). Sows fed diets with 44 mg/kg D-α-TAc had increased (P < 0.03) plasma and colostrum and pig plasma concentrations of α-tocopherol compared with sows fed 44 mg/kg of DL-α-TAc. Sows fed 66 mg/kg DL-α-TAc also had greater (P = 0.022) plasma α-tocopherol at weaning than sows fed 44 mg/kg DL-α-TAc. Bioavailability coefficients for D-α-TAc relative to DL-α-TAc ranged from 1.9 to 4.2 for sow and pig plasma α-tocopherol, 2.9 to 3.6 for colostrum α-tocopherol, 1.6 for milk α-tocopherol, and 1.7 to 2.0 for pig heart and liver α-tocopherol. Overall, this study indicates the bioavailability for D-α-TAc relative to DL-α-TAc varies depending on the response criteria but is greater than the standard potency value of 1.36.

Antimicrobial efficacy of liposome-encapsulated silver ions and tea tree oil against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans.

UNLABELLED: The activity of alternative antimicrobial agents such as tea tree oil (TTO) and silver ions (Ag(+) ) with multiple target sites impedes the development of antibacterial resistance and might be useful in improving the current treatment strategies for various chronic wound infections. In this study, liposome-encapsulated TTO, Ag(+) and TTO plus Ag(+) were added to suspension cultures of Pseudomonas aeruginosa (Ps. aeruginosa), Staphylococcus aureus (Staph. aureus) and Candida albicans (C. albicans). Treatment of these cultures using the agents in combination at subminimal lethal concentrations resulted in an enhanced loss of viability compared to treatment with individual agents. The effective concentration, elimination time (to the limit of detection, LOD) and fractional lethal concentration index (FLCI) of liposomal agents in combination were as follows: Candida albicans: 0·05% v/v TTO:PVA30-70 kDa : 8·9 × 10(-5) % w/v Ag(+) :PVA30-70 kDa : 2·0 h, FLCI = 0·73 (indifferent), Staphylococcus aureus: 0·05% v/v TTO:PVA30-70 kDa : 6·0 × 10(-4) % w/v Ag(+) :PVA30-70 kDa : 1·5 h, FLCI = 0·38 (synergistic), Pseudomonas aeruginosa: 0·25% v/v TTO:PVA30-70 kDa : 3·2 × 10(-4) % w/v Ag(+) :PVA30-70 kDa : 30 min, FLCI = 0·33 (synergistic). These results show the potential for improving antimicrobial efficacy by delivering lower effective concentrations of alternative agents, via controlled release systems. NB All values denoted as %w/vAg(+) refer to the concentration of silver ions. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we have shown that encapsulating silver (as the ion Ag(+) ) and tea tree oil (singly and in combination) in a controlled release liposomal carrier system can improve their antimicrobial efficacy as well as reduce the effective concentration required. These findings may impact on the problems of agent toxicity caused by the need for high effective doses or microbial resistance where long term application is required.

Persistent pollen exposure during infancy is associated with increased risk of subsequent childhood asthma and hayfever.

BACKGROUND: Few studies have focused on pollen exposure and asthma in children. None have examined associations between persistent exposure to pollen in infancy and aeroallergen sensitisation and asthma in childhood. OBJECTIVES: To examine the association between higher ambient levels of pollen in the first 3-6 months of life and risk of eczema, sensitization to food and aeroallergens at 2 years and asthma or hayfever at age 6-7 years combined. METHODS: Using a birth cohort of 620 infants with a family history of allergic disease born between 1990 and 1994, we examined risk of eczema or allergic sensitization (SPT > 3 mm to at least one of cow's milk, egg white, peanut, house dust-mite, rye grass, and cat dander) by age 2 and asthma or hayfever at age 6-7. Daily ambient levels of pollen were measured during this period. RESULTS: Cumulative exposure to pollen concentrations up to 6 months was associated with aeroallergen sensitization with the highest risk occurring at 3 months (aOR = 1.34, 95% CI 1.06-1.72). Cumulative exposure to pollen up to 3 months was also associated with hayfever (aOR = 1.14, 95% CI 1.009-1.29) and between 4 and 6 months exposure with asthma only (aOR=1.35, 95% CI 1.07-1.72). CONCLUSION: Persistent pollen exposure in infancy appears to increase the risk of asthma and hayfever in children. These results support the hypothesis that there is a critical window of opportunity in early development which may be important for modification of allergic outcomes.

Pyoderma gangrenosum: a report of a rare complication after knee arthroplasty requiring muscle flap cover supplemented by negative pressure therapy and hyperbaric oxygen.

Pyoderma gangrenosum (PG) is rare ulcerating skin condition easily confused with wound infection following surgery. We report a complicated case of PG following knee arthroplasty where delayed diagnosis and repeated debridements lead to significant tissue loss. Successful reconstruction was achieved with a muscle flap, but subsequent reactivation of PG and superadded infection placed both the reconstruction and patient's life at risk. Prolonged combined use of negative pressure therapy (NPT), immunosuppression and hyperbaric oxygen (HBO) was successfully used to reduce the wound size, enhance wound granulation, promote re-epithelialisation, and provide pain relief. There is little or no published literature on these treatment modalities for the management of PG, with only one reported case using both NPT and HBO for PG (not following knee arthroplasty). More studies are necessary to determine the role of both modalities in the management of pathergy in large and complex wounds and the rare nature of this complication following knee arthroplasty explains the lack of evidence-based guidance. In conclusion, we suggest a surgical algorithm. This is the first report of PG following knee arthroplasty with the use of both NPT and HBO in order to achieve soft tissue coverage.

Antimicrobial efficacy of silver ions in combination with tea tree oil against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans.

Tea tree oil (TTO) and silver ions (Ag(+)), either alone or in combination with other antimicrobial compounds, have been used in the treatment of topical infections. However, there appears to be little data on the efficacy of TTO combined with silver in the absence of any other agents. TTO and Ag(+) were added, alone and in combination, to suspension cultures of Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Treatment of these cultures with TTO and Ag(+) at sub-minimal lethal concentrations resulted in an enhanced loss of viability compared with treatment with individual agents. The order of sensitivity to the combined agents was P. aeruginosa>S. aureus>C. albicans. The fractional lethal concentration index (FLCI) showed that these combinations of TTO and Ag(+) exerted a synergistic effect against P. aeruginosa (FLCI=0.263) and an indifferent effect against S. aureus and C. albicans (FLCI=0.663 and 1.197, respectively). The results indicate that combining these antimicrobial agents may be useful in decreasing the concentration of antimicrobial agents required to achieve an effective reduction in opportunistic pathogenic microorganisms that typically infect wounds.

Counseling patients about hormone therapy and alternatives for menopausal symptoms.

The results of recent large clinical trials have led physicians and patients to question the safety of menopausal hormone therapy. In the past, physicians prescribed hormone therapy in an attempt to improve overall health and prevent cardiac disease. Hormone therapy appears to increase the risk of breast cancer when used for more than three to five years; therefore, regulatory agencies now advise that physicians prescribe it only to treat menopausal symptoms such as hot flashes and vaginal atrophy, with the smallest effective dosage and for the shortest possible duration. Although estrogen is the most effective treatment for hot flashes, alternatives such as venlafaxine and gabapentin are effective for some patients. Herbal formulations such as dong quai, ginseng, kava, and dietary soy, among others, do not appear to benefit patients more than placebo. In contrast to systemic estrogen therapy, topical estrogen therapy for vulvovaginal atrophy is more appealing for certain patients because it does not require the addition of a progestogen for endometrial protection. Some have advocated selective estrogen reuptake modulators as alternatives to hormone therapy for the prevention of menopausal osteoporosis. The decision to use either therapy depends on clinical presentation and a thorough evaluation of the risks and benefits, because both have potential detrimental health effects and both are linked to an increased risk of venous thromboembolism.

Electronic prescribing influence on calcium supplementation: a randomized controlled trial.

OBJECTIVE: The purpose of this study was to determine whether an electronic prescription for over-the-counter calcium supplements increases compliance. STUDY DESIGN: Two hundred forty-five patients from 19-50 years of age who underwent annual gynecologic examinations were assigned randomly to either verbal counseling about the use of a calcium carbonate with vitamin D supplement (n = 122) or verbal counseling and an electronic prescription (n = 123). Telephone interviews at 3 and 6 months determined compliance. RESULTS: Women who received the electronic prescription were significantly more likely to use calcium supplementation than control subjects at both 3 and 6 months. At 3 months, 66.0% of women who received an electronic prescription reported compliance (P = .001). At 6 months, 57.0% of the participants were compliant (P = .001). At 6 months, women who were given the electronic prescription were 2.2 times more likely to report having taken the calcium than were control subjects (95% confidence interval, 1.5-3.1). CONCLUSION: An electronic prescription for over-the-counter calcium supplements is associated with a significant increase in compliance, compared with verbal counseling alone.

Effect of vitamin E source, natural versus synthetic, and quantity on serum and tissue alpha-tocopherol concentrations in finishing swine.

Relative vitamin E status of pigs fed natural or synthetic vitamin E was evaluated based on serum and tissue alpha-tocopherol concentrations. Individually fed finishing gilts at a BW of 70.5 kg (n = 24) were allotted to dietary treatments based on initial BW. The 5 dietary treatments consisted of a positive control diet using synthetic vitamin E acetate (Syn E Ac) supplemented at 22 mg/kg, and 4 dietary levels of natural vitamin E acetate (Nat E Ac) supplemented at 6.71, 8.33, 11.00, and 16.18 mg/kg of diet. Before initiation of the 32-d experiment, pigs were fed a non-vitamin E-fortified diet for 30 d. Diets were formulated to contain true ileal digestible lysine of 0.9 and 0.8% for the pretest and test diets. Serum samples were collected on d 15 and 32, whereas tissue samples were collected on d 32 for alpha-tocopherol analysis. Serum alpha-tocopherol concentrations on d 15 and 32 were greater (P < 0.05) in pigs fed 8.33, 11.00, or 16.18 mg/kg of Nat E Ac than in pigs fed 22 mg/kg of Syn E Ac. When compared with pigs fed 22 mg/kg of Syn E Ac, alpha-tocopherol concentrations were greater (P < 0.05) in 6 tissues (heart, kidney, spleen, liver, lung, and adipose) in pigs fed 16.18 mg/kg of Nat E Ac; greater (P < 0.05) in heart, kidney, spleen, liver, and adipose tissue in pigs fed 11.00 mg/kg of Nat E Ac; and greater (P < 0.05) in spleen, loin, and adipose tissue in pigs fed 8.33 mg/kg of Nat E Ac. As dietary Nat E Ac increased from 6.71 to 16.18 mg/kg, serum alpha-tocopherol increased linearly (P < 0.01) on d 15 and 32 of the experiment. Increasing dietary Nat E Ac linearly increased (P < 0.05) alpha-tocopherol concentrations for lung, heart, kidney, spleen, and liver. These results indicate that Nat E Ac was an effective vitamin E source and its relative bioavailability was substantially greater than 1.36 for finishing swine when compared with Syn E Ac.

Preconception counseling: make it part of the annual exam.

Supplementing women's diets with 400 mcg folic acid every day reduces the incidence of neural tube defects in their offspring by up to 72%. Optimizing diabetic glucose control prior to conception is linked to a reduction in birth defects and pregnancy loss. Limiting caffeine consumption to no more than 200 mg per day may reduce the risk of miscarriage.

Associations between fatty acids in colostrum and breast milk and risk of allergic disease.

BACKGROUND: Exposure to n-3 polyunsaturated fatty acids (PUFA) in early life is hypothesized to offer protection against atopic disease. However, there is controversy in this area, and we have previously observed that high levels of n-3 fatty acid (FA) in colostrum are associated with increased risk of allergic sensitization. OBJECTIVE: The aim of the study was to assess the relationship between FA profile in breast milk and risk of childhood atopic disease. METHODS: A high-risk birth cohort was recruited, and a total of 224 mothers provided a sample of colostrum (n=194) and/or 3-month expressed breast milk (n=118). FA concentrations were determined by gas chromatography. Presence of eczema, asthma and rhinitis were prospectively documented up to 7 years of age. RESULTS: High levels of n-3 22:5 FA (docosapentaenoic acid, DPA) in colostrum were associated with increased risk of infantile atopic eczema [odds ratio (OR)=1.66 per 1 standard deviation increase, 95% confidence interval (CI)=1.11-2.48], while total n-3 concentration in breast milk was associated with increased risk of non-atopic eczema (OR=1.60, 95% CI=1.03-2.50). Higher levels of total n-6 FA in colostrum were associated with increased risk of childhood rhinitis (OR=1.59, 95% CI=1.12-2.25). There was no evidence of associations between FA profile and risk of asthma. CONCLUSION: In this cohort of high-risk children, a number of modest associations were observed between FA concentrations in colostrum and breast milk and allergic disease outcomes. Further research in this area with larger sample sizes is needed.

Motion-enhanced, differential interference contrast (MEDIC) microscopy of moving vesicles in live cells: VE-DIC updated.

Video-enhanced differential interference contrast microscopy with background subtraction has made visible many structures and processes in living cells. In video-enhanced differential interference contrast, the background image is stored manually by defocusing the microscope before images are acquired. We have updated and improved video-enhanced differential interference contrast by adding automatic generation of the background image as a rolling average of the incoming image stream. Subtraction of this continuously updated 12-bit background image from the incoming 12-bit image stream provides a flat background which allows the contrast of moving objects, such as vesicles, to be strongly enhanced while suppressing stationary features such as the overall cell shape. We call our method MEDIC, for motion-enhanced differential interference contrast. By carrying out background subtraction with 12-bit images, the number of grey levels in the moving vesicles can be maximized and a single look-up table can be applied to the entire image, enhancing the contrast of all vesicles simultaneously. Contrast is increased by as much as a factor of 13. The method is illustrated with raw, background and motion-enhanced differential interference contrast images of moving vesicles within a neurite of a live PC12 cell and a live chick motorneuron.

20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol, a novel natural product for prostate cancer therapy: activity in vitro and in vivo and mechanisms of action.

We recently isolated 20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol (25-OCH3-PPD), a natural product from Panax notoginseng, and demonstrated its cytotoxicity against a variety of cancer cells. Here we report the effects of this compound in vitro and in vivo on human prostate cancer cells, LNCaP (androgen-dependent) and PC3 (androgen-independent), in comparison with three structurally related ginsenosides, ginsenoside Rh2, ginsenoside Rg3, and 20(S)-protopanaxadiol. Of the four test compounds, 25-OCH3-PPD was most potent. It decreased survival, inhibited proliferation, induced apoptosis, and led to G1 cell cycle arrest in both cell lines. It also decreased the levels of proteins associated with cell proliferation (MDM2, E2F1, cyclin D1, and cdks 2 and 4) and increased or activated pro-apoptotic proteins (cleaved PARP, cleaved caspase-3, -8, and -9). In LNCaP cells, 25-OCH3-PPD inhibited the expression of the androgen receptor and prostate-specific antigen. Moreover, 25-OCH3-PPD inhibited the growth of prostate cancer xenograft tumours. Combining 25-OCH3-PPD with conventional chemotherapeutic agents or with radiation led to potent antitumour effects; tumour regression was almost complete following administration of 25-OCH3-PPD and either taxotere or gemcitabine. 25-OCH3-PPD also demonstrated low toxicity to noncancer cells and no observable toxicity in animals. In conclusion, our preclinical data indicate that 25-OCH3-PPD is a potential therapeutic agent against both androgen-dependent and androgen-independent prostate cancer.

An evaluation of natural (RRR-alpha-tocopheryl acetate) and synthetic (all-rac-alpha-tocopheryl acetate) vitamin E fortification in the diet or drinking water of weanling pigs.

Three experiments conducted with weanling pigs evaluated the effects of vitamin E added to the drinking water or diet on plasma and tissue alpha-tocopherol concentrations. When natural or synthetic vitamin E was used, it was added at an IU-equivalent basis, but natural vitamin E was 73.5% (mg basis) of the synthetic vitamin E. Experiment 1 used 18-d-old weanling pigs (n = 120) in a 3 x 2 factorial arrangement of treatments in a randomized complete block design with 4 replicates. The first factor evaluated the dietary levels of natural vitamin E (RRR-alpha-tocopheryl acetate) added at 0, 50, or 300 IU/kg, whereas the second factor was the natural vitamin E added to the drinking water at 0 or 100 IU/L. Pigs were bled at periodic intervals, and 1 pig per pen was killed at the end of the 21-d trial and tissues (liver, heart, lung, and loin) were collected for alpha-tocopherol analysis. When vitamin E was not added to the diet or water, plasma alpha-tocopherol declined over the 21-d period. Although there were some interactions (P < 0.01), tissue and plasma alpha-tocopherol concentrations increased linearly when vitamin E was added to the diet or water. Experiment 2 was a 3 x 2 factorial in a randomized complete block design with 4 replicates. A total of 96 pigs weaned at 18 d of age, with an initial BW of 6.2 kg, were fed a nonvitamin E fortified diet, but natural or synthetic (all-rac-alpha-tocopheryl acetate) vitamin E was added to their drinking water at 50, 100, or 150 IU/L. Pigs were bled at 0, 3, 7, 10, 14, and 21 d postweaning, with tissues (liver, lung, heart, and loin) collected for alpha-tocopherol analysis at d 21. The results indicated that plasma alpha-tocopherol concentrations increased (P < 0.01) as vitamin E increased, with greater tissue alpha-tocopherol concentrations (P < 0.01) when natural vitamin E was provided. Experiment 3 was conducted in 2 replicates, but pigs (n = 60) were not provided vitamin E in the diet or water for 7 d postweaning, and then natural or synthetic vitamin E was added to the drinking water as in Exp. 2 (50, 100, or 150 IU/L). Pigs were bled at 0, 2, 4, 6, 8, 10, and 24 h after being provided vitamin E to evaluate the absorption from each vitamin E source and level. Plasma alpha-tocopherol increased quadratically (P < 0.01) and plateaued at 8 to 10 h for each treatment group. These results indicate that adding vitamin E to the pig's water supply at weaning was more effective in increasing plasma alpha-tocopherol than when it was added to the diet during the initial 14 d postweaning, and that natural vitamin E was a superior source compared with synthetic vitamin E.

The effect of simulated gastric environments on the anti-Helicobacter activity of garlic oil.

AIMS: To investigate the effects of simulated gastric conditions upon the anti-Helicobacter pylori effects of garlic oil (GO). METHODS AND RESULTS: Time course viability experiments assessed the anti-H. pylori activity of GO (16 and 32 microg ml(-1)) in simulated gastric environments. Rapid anti-H. pylori action of GO was observed in artificial gastric juice. Mucus (1-5%) was strongly protective of H. pylori both alone and in the presence of GO, but its protective effect was antagonized by GO. Peptone (5-15 g l(-1)) caused a dose-dependent reduction in the anti-H. pylori activity of GO. Rapeseed oil (5.7-17 g l(-1)) greatly diminished the anti-H. pylori activity of GO. Dextrin (44 and 133 g l(-1)) exhibited direct anti-H. pylori effects and added to those of GO. Simulated meal mixtures decreased but did not eliminate the anti-H. pylori activity of 32 mug ml(-1) GO. CONCLUSIONS: The anti-H. pylori activity of GO was noticeably affected by food materials and mucin. However, substantial activity remained under simulated gastric conditions. Further investigation of the therapeutic potential of GO against H. pylori is therefore warranted. SIGNIFICANCE AND IMPACT OF THE STUDY: Garlic oil may be useful as an alternative treatment against H. pylori, a major cause of gastrointestinal infections in humans.

The development of a new three-step protocol to determine the efficacy of disinfectant wipes on surfaces contaminated with Staphylococcus aureus.

We developed a three-step protocol to quantify the efficacy of disinfectant wipes, their ability to remove and prevent microbial transfer from surfaces and their overall antimicrobial activity. Meticillin-resistant (MRSA) or -susceptible (MSSA) Staphylococcus aureus (6-7 log(10)cfu) were inoculated onto stainless steel discs with or without organic load and dried. Grapefruit extract-containing test wipes and unmedicated control wipes were used. In step 1, wipes were mechanically rotated against surfaces for 10s at 60rpm, exerting a weight of 100+/-5g. Bacterial removal was assessed by transferring the steel discs to neutraliser, resuspending and counting remaining bacteria. In step 2, bacterial transfer from wipes was assessed by eight consecutive mechanical adpression transfers to agar/neutraliser plates. Step 3 was the measurement of antimicrobial activity by direct inoculation of the wipes for 10s followed by neutralisation and enumeration. Test wipes achieved a significantly higher bacterial cell removal than control wipes on all surfaces (P<0.05). The low bactericidal activity of the wipes (<1 log(10) reduction when directly inoculated) and the subsequent survival of bacteria on the wipes, however, led to repeated microbial transfer when initially high contamination levels were present. There were no differences between MRSA and MSSA in removal, transfer or antimicrobial activity. The three-step method is a useful tool for developing future guidelines to assess the ability of wipes to disinfect surfaces.

Isolation, structural determination, and evaluation of the biological activity of 20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol [20(S)-25-OCH3-PPD], a novel natural product from Panax notoginseng.

Ginseng has been used extensively for medicinal purposes, with suggested utility for indications as diverse as diabetes, cardiovascular disease and cancer. Herein we report the discovery and characterization of 20(S)-25-OCH3-PPD, a ginsenoside that inhibits growth and survival of cancer cells. The novel dammarane triterpene sapogenin (C31H56O4; molecular weight 492) was isolated from the total hydrolyzed saponins extracted from the leaves of Panax notoginseng using conventional and reverse-phase silica gel chromatography. Based on physicochemical characteristics and NMR data, the compound was identified as 20(S)-25-OCH3-PPD. The biological activities of 20(S)-25-OCH3-PPD and its known analogs, 20(S)-PPD and Rg3, were evaluated in 12 human cancer cell lines. In all cell lines, the order of cytotoxicity of the test compounds was 20(S)-25-OCH3-PPD >> 20(S)-PPD >> Rg3. 20(S)-25-OCH3-PPD also induced apoptosis and cell cycle arrest in the G1 phase, and inhibited proliferation in breast cancer cell lines, demonstrating its potent biological effects. In regard to cytotoxicity, the IC50 values of 20(S)-25-OCH3-PPD for most cell lines were in the lower microM range, a 5-15-fold greater cytotoxicity relative to 20(S)-PPD and a 10-100-fold increase over Rg3. These findings suggest a structure-activity relationship among dammarane-type sapogenins. The data presented here may provide a basis for the future development of 20(S)-25-OCH3-PPD as a novel anti-cancer agent.

Taurine supplement in early life altered islet morphology, decreased insulitis and delayed the onset of diabetes in non-obese diabetic mice.

AIMS/HYPOTHESIS: We hypothesised that nutritional taurine, which is important for the development of the endocrine pancreas and reduces cytokine-induced apoptosis in pancreatic beta cells, would prevent or delay the onset of autoimmune diabetes, if given early in life to the non-obese diabetic (NOD) mouse. METHODS: Pregnant NOD mice received a diet supplemented with taurine throughout gestation or until weaning, and the pancreas of the offspring was examined using immunohistochemistry. This was done at postnatal day 14 and after 8 weeks (assessment of insulitis). The animals were also monitored until they became diabetic. RESULTS: At 14 days, pancreatic islet mass was significantly greater in animals treated with taurine than in controls. This finding was associated with a greater incidence of islet cell proliferation and a lower incidence of apoptosis. At age 8 weeks the number of islets manifesting insulitis was reduced by more than half, and the area of insulitis was reduced by 90%. Taurine treatment delayed the mean onset time of diabetes from 18 to 30 weeks in females, and from 30 to 38 weeks in males, while 20% of treated females remained free of diabetes after one year. CONCLUSIONS/INTERPRETATION: Taurine supplementation in early life altered islet development, reduced insulitis and delayed the onset of diabetes in NOD mice.

Low-protein diet during early life causes a reduction in the frequency of cells immunopositive for nestin and CD34 in both pancreatic ducts and islets in the rat.

Feeding a low-protein (LP) diet to pregnant and lactating rats impairs pancreatic islet mass and insulin release in the offspring, leading to glucose intolerance as adults. We hypothesized that an LP diet changes the number of pancreatic endocrine precursor cells or cells supporting endocrine cell neogenesis. Pregnant rats were given LP (8% protein) or a control (20% protein) diet from conception until postnatal d 21. Cells containing nestin, CD34, or c-Kit were quantified in pancreata of the offspring. Stellate cells immunoreactive for nestin were seen to be adjacent to ductal epithelium and were resident within the islets. These were proliferative and immunonegative for cytokeratin 20, fibronectin, tyrosine hydroxylase, pancreatic duodenal homeobox 1, Nk homeodomain transcription factor 6.1, or insulin, but expressed vimentin. Approximately 20% of islet nestin-positive cells also expressed the endothelial cell marker platelet endothelial cell adhesion molecule-1. Both ducts and islets also contained CD34- and c-Kit-positive cells with similar morphology to those expressing nestin. Offspring from rats fed the LP diet had significantly less nestin/CD34-positive cells and reduced expression of nestin mRNA. Within islets, there was an associated decrease in cell proliferation and in cells immunopositive for pancreatic duodenal homeobox 1. Nestin-positive cell number within islets correlated positively with the percent area of beta-cells. Supplementation of pregnant and lactating rats with taurine reversed the deficits in mean islet area and nestin-positive cells caused by the LP diet within the islets of the offspring. Nutritional programming of postnatal beta-cell mass may involve an altered abundance of cells expressing nestin and/or CD34, which may limit endocrine cell development.

Maternal breast milk long-chain n-3 fatty acids are associated with increased risk of atopy in breastfed infants.

BACKGROUND: Australia has one of the highest prevalence rates internationally of allergic conditions, such as asthma and eczema. Atopy is one hallmark for the development of allergic disease and predisposes to allergic inflammation in the target organs. omega-3 (n-3) fatty acids (FAs) are thought to act as precursors to the formation of less active inflammatory mediators, with the potential to reduce inflammation. OBJECTIVE: To investigate whether increased n-3 FA levels in maternal breast milk are associated with a lower risk of developing atopy in infancy. METHODS: Subjects were part of the prospective Melbourne atopy cohort study, which involved 620 children born into families where at least one first-degree relative had an atopic disease. Some 224 women (mean age 31.4+/-4.2 (SD) years, with 73.2% (n=164) having self-reported atopy) provided either a colostrum (n=194) or 3-month expressed breast milk (EBM) sample (n=118). Maternal colostrum and 3-month EBM samples were analysed for FA content by gas chromatography. Skin prick tests (SPTs) to six common allergens were performed on infants at 6, 12 and 24 months of age and on mothers who agreed at study entry. RESULTS: For infants sensitized to foods at 6 months (n=29), the total n-3 FA level in the colostrum was significantly higher (P=0.004) as were levels of individual long-chain n-3 FAs, docosoapentaenoic acid (DPA, C22:5, P=0.001) and docosahexaenoic acid (DHA, C22:6, P=0.002) than in non-sensitized infants. Infants with aero-allergen sensitization at 24 months (n=30) had higher levels of the n-3 FA, DPA (P=0.002) and DHA (P=0.007), and similarly higher total n-3 FA (P=0.009) in maternal colostrum than those infants who were not sensitized. CONCLUSION: Higher n-3 FA levels in the colostrum do not appear to confer protection against, but may be a risk factor for, the eventual development of atopy in high-risk breastfed infants.