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BPA increases risk of cancer in human prostate tissue

BPA increases risk of cancer in human prostate tissue | A Tale of Two Medicines | Scoop.it

Fetal exposure to a commonly used plasticizer found in products such as water bottles, soup can liners and paper receipts can increase the risk for prostate cancer later in life, according to a study from the University of Illinois at Chicago published Jan. 7 online in the journal Endocrinology.

 

Bisphenol A, or BPA, is widely used to soften plastics. Steering clear of the chemical is nearly impossible, says Gail Prins, professor of physiology at UIC and lead author of the paper.

 

“Previous studies have shown that people who avoided all contact with plastics or other BPA-containing objects for up to a month or more still had BPA in their urine, which means they must have come into contact with BPA in the last 24 to 48 hours, since it clears the body rather quickly,” said Prins, who is director of the UIC andrology laboratory. “It’s very hard to avoid.”

 

Exposure of the fetus to BPA in utero is of particular concern, because the chemical, which mimics the hormone estrogen, has been linked to several kinds of cancer, including prostate cancer, in rodent models. The new findings show that human prostate tissue is also susceptible.

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A Tale of Two Medicines
Natural Medicine, Pharmaceuticals and GMO’s, the Good, the Bad and the OMG! - (The information provided is not intended to be a substitute for professional medical advice, diagnosis or treatment.  Never disregard professional medical advice, or delay in seeking it, because of something you have read on this scoopit page.)
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pH dependent antioxidant activity of lettuce (L. sativa) and synergism with added phenolic antioxidants.

pH dependent antioxidant activity of lettuce (L. sativa) and synergism with added phenolic antioxidants. | A Tale of Two Medicines | Scoop.it
Influence of pH on the antioxidant activities of combinations of lettuce extract (LE) with quercetin (QC), green tea extract (GTE) or grape seed extract (GSE) was investigated for both reduction of Fremy's salt in aqueous solution using direct electron spin resonance (ESR) spectroscopy and in l-α-phosphatidylcholine liposome peroxidation assay measured following formation of conjugated dienes. All examined phenolic antioxidants showed increasing radical scavenging effect with increasing pH values by using both methods. QC, GTE and GSE acted synergistically in combination with LE against oxidation of peroxidating liposomes and with QC showing the largest effect. The pH dependent increase of the antioxidant activity of the phenols is due to an increase of their electron-donating ability upon deprotonation and to their stabilization in alkaline solutions leading to polymerization reaction. Such polymerization reactions of polyphenolic antioxidants can form new oxidizable -OH moieties in their polymeric products resulting in a higher radical scavenging activity.
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Stability of the Ellagitannin Fraction and Antioxidant Capacity of Varietal Pomegranate Juices.

Stability of the Ellagitannin Fraction and Antioxidant Capacity of Varietal Pomegranate Juices. | A Tale of Two Medicines | Scoop.it
This work aimed to assess the effect of combining two pomegranate (Punica granatum L.) cultivars at different rates on the ellagitannin content, antioxidant capacity, and total phenolic content of varietal pomegranate juices. Widely distinct juices made from Mollar de Elche and Wonderful cultivars were used for the elaboration of blended juices. They were stored for 70 days at both room and refrigeration temperatures. This study revealed a significant cultivar effect on the stability of main pomegranate ellagitannins (punicalagins, punicalins, punicalagin-like compound, and ellagic acid derivatives) and on the antioxidant capacity measured by the ABTS+ and DPPH* in vitro assays. Blended juices enhanced and/or retained the initial ellagitannin content and antioxidant capacity of pure juices during storage. Thus, blending varietal juices could be suggested as a promising alternative to the development of fresh juices with a high, stable phytochemical load.
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Vitamin D3 potentiates myelination and recovery after facial nerve injury.

Vitamin D3 potentiates myelination and recovery after facial nerve injury. | A Tale of Two Medicines | Scoop.it
Roles of vitamin D on the immune and nervous systems are increasingly recognized. Two previous studies demonstrated that ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) induced functional recovery and increased myelination in a rat model of peroneal nerve transection. The current report assessed whether cholecalciferol was efficient in repairing transected rabbit facial nerves. Animals were randomized into two groups of rabbits with an unilateral facial nerve surgery: the vitamin D group included animals receiving a weekly oral bolus of vitamin D3 (200 IU/kg/day), from day 1 post-surgery; the control group included animals receiving a weekly oral bolus of vehicle (triglycerides). Contralateral unsectioned facial nerves from all experimental animals were used as controls for the histological study. The facial functional index was measured every week while the inner diameter of myelin sheath and the G ratio were quantified at the end of the 3 month experiment. The current report indicates that cholecalciferol significantly increases functional recovery and myelination, after 12 weeks of treatment. To the best of our knowledge, this is the first study investigating the therapeutic benefit of vitamin D supplementation in an animal model of facial paralysis. It paves further the way for clinical trials based on the administration of this steroid in individuals with injured facial nerves.
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Toxoplasma gondii seropositivity and cognitive functions in school-aged children.

Toxoplasma gondii seropositivity and cognitive functions in school-aged children. | A Tale of Two Medicines | Scoop.it
Toxoplasma gondii (T. gondii) infects one-third of the world population, but its association with cognitive functions in school-aged children is unclear. We examined the relationship between Toxoplasma seropositivity and neuropsychological tests scores (including math, reading, visuospatial reasoning and verbal memory) in 1755 school-aged children 12-16 years old who participated to the Third National Health and Nutrition Examination Survey, using multiple linear regressions adjusted for covariates. Toxoplasma seroprevalence was 7·7% and seropositivity to the parasite was associated with lower reading skills (regression coefficient [β] = -5·86, 95% confidence interval [CI]: -11·11, -0·61, P = 0·029) and memory capacities (β = -0·86, 95% CI: -1·58, -0·15, P = 0·017). The interaction between T. gondii seropositivity and vitamin E significantly correlated with memory scores. In subgroup analysis, Toxoplasma-associated memory impairment was worse in children with lower serum vitamin E concentrations (β = -1·61, 95% CI: -2·44, -0·77, P < 0·001) than in those with higher values (β = -0·12, 95% CI: -1·23, 0·99, P = 0·83). In conclusion, Toxoplasma seropositivity may be associated with reading and memory impairments in school-aged children. Serum vitamin E seems to modify the relationship between the parasitic infection and memory deficiency.
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Vitamin B2 sensitizes cancer cells to vitamin C-induced apoptosis via modulation of Akt and Bad phosphorylation.

Vitamin B2 sensitizes cancer cells to vitamin C-induced apoptosis via modulation of Akt and Bad phosphorylation. | A Tale of Two Medicines | Scoop.it
Vitamin C is an essential dietary nutrient that has a variety of biological functions. Recent studies have provided promising evidence for its additional health benefits including anti-cancer activity. Vitamin B2, another essential dietary nutrient, is often coexisted with vitamin C in some fruits, vegetables or dietary supplements. The objective of the present study is to determine whether combination of vitamin C and B2 can achieve a synergistic anti-cancer activity. MDA-MB-231, MCF-7 and A549 cells were employed to evaluate the combinatory effects of vitamin C and B2. We found that combination of vitamin C and vitamin B2 resulted in a synergistic cell death induction in all cell lines tested. Further mechanistic investigations revealed that vitamin B2 sensitized cancer cells to vitamin C through inhibition of Akt and Bad phosphorylation. Our findings identified vitamin B2 as a promising sensitizer for improving the efficacy of vitamin C-based cancer chemoprevention and chemotherapy.
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Enhanced absorption and pharmacokinetics of fresh turmeric (Curcuma Longa L) derived curcuminoids in comparison with the standard curcumin from dried rhizomes

Despite the various attempts to overcome the poor oral bioavailability of curcuminoids isolated from dried turmeric, no attempt has so far been reported on fresh turmeric derived curcuminoids. Herein, we report a novel preparation of curcuminoids from fresh turmeric rhizomes (FTC) as amorphous water soluble stable powder and its enhanced absorption and pharmacokinetics in comparison with 95% pure curcuminoids isolated from dried turmeric (DTC). While the oral administration of FTC at 250 mg/kg body weight was found to offer significant levels of plasma curcumin in Wistar rats for longer duration, an equivalent dose of curcuminoids as DTC failed to produce detectable plasma levels. Dose dependent human studies (100, 250 and 1000 mg doses of FTC) also showed significant (p < 0.001) absorption of total curcuminoids (46-fold) and free unconjugated curcuminoids from FTC with improved pharmacokinetics as compared to equivalent doses of curcuminoids as DTC.
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MR-guided focused ultrasound (MRgFUS) ablation for the treatment of nonspinal osteoid osteoma: a prospective multicenter evaluation.

MR-guided focused ultrasound (MRgFUS) ablation for the treatment of nonspinal osteoid osteoma: a prospective multicenter evaluation. | A Tale of Two Medicines | Scoop.it

Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel imaging-guided surgical technique that allows the performance of noninvasive and radiation-free ablation. Presently, computed tomography (CT)-guided radiofrequency ablation, a minimally invasive percutaneous technique, is the standard for treating symptomatic osteoid osteomas. The purpose of this study was to evaluate the use of MRgFUS ablation for the treatment of nonspinal osteoid osteomas in terms of technical success, complications, and clinical success through one year of follow-up.

In this prospective multicenter study, thirty consecutive patients with a nonspinal osteoid osteoma were enrolled between May 2010 and April 2012 at three different university centers; twenty-nine of the patients were treated with use of MRgFUS. Lesions had been previously diagnosed on the basis of imaging, including dynamic contrast-enhanced MR. The mean number of sonications and energy deposition were determined. Technical success was evaluated through an assessment of complications immediately after treatment. Clinical success was determined on the basis of pain reduction as measured with a visual analog scale (VAS), recurrence, and long-term complications through twelve months.

Technical success of MRgFUS was observed for all twenty-nine patients. The mean number of sonications (and standard deviation) was 7 ± 3, and the mean delivered acoustic energy was 1180 ± 736 J. At the twelve-month follow-up, complete clinical success was observed in twenty-six (90%) of the twenty-nine patients (95% confidence interval [CI] = 84 to 95; mean VAS, 0 ± 0 points). Partial success was observed in three (10%) of the twenty-nine patients (95% CI = 5 to 16; mean VAS score, 5 ± 0 points); two of these patients subsequently underwent CT-guided radiofrequency ablation, and one underwent open surgery. Pain score values showed a significant reduction (p < 0.001) between baseline (mean VAS score, 8 ± 1 points) and post treatment (mean VAS score, 1 ± 2 points). No complications were observed.

MRgFUS may be an effective and safe alternative approach in the treatment of nonspinal osteoid osteoma. A complete clinical success rate of 90% was demonstrated without adverse events. MRgFUS is totally noninvasive and eliminates radiation exposure.

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Incidence rate of type 2 diabetes is >50% lower in grassroots health cohort with median serum 25–hydroxyvitamin d of 41ng/ml than in nhanes cohort with median of 22ng/ml

Incidence rate of type 2 diabetes is >50% lower in grassroots health cohort with median serum 25–hydroxyvitamin d of 41ng/ml than in nhanes cohort with median of 22ng/ml | A Tale of Two Medicines | Scoop.it
Higher serum 25–hydroxyvitamin D [25(OH)D] concentrations have been associated with lower risk of type 2 diabetes. This study compared incidence rates of type 2 diabetes among participants aged ≥20 years in two U.S. cohorts with markedly different median 25(OH)D concentrations. The median 25(OH)D concentration in the Grassroots Health (GRH) cohort was 41 ng/ml (N = 4933) while in the 2005–6 National Health and Nutrition Examination Survey (NHANES) it was 22 ng/ml (N = 4078) (P < 0.0001). The adjusted annual incidence rate of type 2 diabetes was 3.7 per 1000 population (95% confidence interval = 1.9, 6.6) in the GRH cohort, compared to 9.3 per 1000 population (95% confidence interval = 6.7, 12.6) in NHANES. In the NHANES cohort, the lowest 25(OH)D tertiles (<17, 17–24 ng/ml) had higher odds of developing diabetes than the highest tertile (OR: 4.9, P = 0.02 and 4.8, P = 0.01 respectively), adjusting for covariates. Differences in demographics and methods may have limited comparability. Raising serum 25(OH)D may be a useful tool for reducing risk of diabetes in the population.
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Interplay of glia activation and oxidative stress formation in fluoride and aluminium exposure.

Interplay of glia activation and oxidative stress formation in fluoride and aluminium exposure. | A Tale of Two Medicines | Scoop.it

Oxidative stress formation is pivotal in the action of environmental agents which trigger the activation of glial cells and neuroinflammation to stimulate compensatory mechanisms aimed at restoring homeostasis.

This study sets to demonstrate the interplay of fluoride (F) and aluminium (Al) in brain metabolism. Specifically, it reveals how oxidative stress impacts the activation of astrocytes (GFAP), mediates proinflammatory responses (microglia and B-cells: CD68 and CD 20 respectively) and shows the pattern of lipid peroxidation in the brain following fluoride and (or) aluminium treatment in vivo.

Male adult Wistar rats were treated with low and high doses of fluoride, aluminium or combination of fluoride-aluminium for 30 days. The control group received distilled water for the duration of the treatment. Blood and brain tissue homogenates were prepared for colorimetric assay of stress biomarkers [malonialdehyde (MDA) and superoxide dismutase (SOD)]. Subsequent analysis involved immunodetection of astrocytes (anti-GFAP), microglial (anti-CD68) and B-cells (anti-CD20) in coronal sections of the prefrontal cortex using antigen retrieval immunohistochemistry.

Aluminium, fluoride and a combination of aluminium-fluoride treatments caused an increase in brain lipid peroxidation products and reactive oxygen species (ROS) formation. Similarly, an increase in glial activation and inflammatory response were seen in these groups versus the control. Oxidative stress induced glial activation (GFAP) and increased the expression of B cells (CD20). This also corresponded to the extent of tissue damage and lipid peroxidation observed. Taken together, the results suggest a close link between oxidative stress neuroinflamation and degeneration in aluminium-fluoride toxicity.

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Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death.

Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death. | A Tale of Two Medicines | Scoop.it
Treatment regimens for acute myeloid leukemia (AML) continue to offer weak clinical outcomes. Through a high-throughput cell-based screen, we identified avocatin B, a lipid derived from avocado fruit, as a novel compound with cytotoxic activity in AML. Avocatin B reduced human primary AML cell viability without effect on normal peripheral blood stem cells. Functional stem cell assays demonstrated selectivity toward AML progenitor and stem cells without effects on normal hematopoietic stem cells. Mechanistic investigations indicated that cytotoxicity relied on mitochondrial localization, as cells lacking functional mitochondria or CPT1, the enzyme that facilitates mitochondria lipid transport, were insensitive to avocatin B. Furthermore, avocatin B inhibited fatty acid oxidation and decreased NADPH levels, resulting in ROS-dependent leukemia cell death characterized by the release of mitochondrial proteins, apoptosis-inducing factor, and cytochrome c. This study reveals a novel strategy for selective leukemia cell eradication based on a specific difference in mitochondrial function.
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Selective Antibacterial Activity of Patchouli Alcohol Against Helicobacter pylori Based on Inhibition of Urease.

Selective Antibacterial Activity of Patchouli Alcohol Against Helicobacter pylori Based on Inhibition of Urease. | A Tale of Two Medicines | Scoop.it
The aim of this study is to evaluate the antibacterial activity and urease inhibitory effects of patchouli alcohol (PA), the bioactive ingredient isolated from Pogostemonis Herba, which has been widely used for the treatment of gastrointestinal disorders. The activities of PA against selected bacteria and fungi were determined by agar dilution method. It was demonstrated that PA exhibited selective antibacterial activity against Helicobacter pylori, without influencing the major normal gastrointestinal bacteria. Noticeably, the antibacterial activity of PA was superior to that of amoxicillin, with minimal inhibition concentration value of 78 µg/mL. On the other hand, PA inhibited ureases from H. pylori and jack bean in concentration-dependent fashion with IC50 values of 2.67 ± 0.79 mM and 2.99 ± 0.41 mM, respectively. Lineweaver-Burk plots indicated that the type of inhibition was non-competitive against H. pylori urease whereas uncompetitive against jack bean urease. Reactivation of PA-inactivated urease assay showed DL-dithiothreitol, the thiol reagent, synergistically inactivated urease with PA instead of enzymatic activity recovery. In conclusion, the selective H. pylori antibacterial activity along with urease inhibitory potential of PA could make it a possible drug candidate for the treatment of H. pylori infection.
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Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and 4T1 breast cancer cells in vitamin C-deficient mice

Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and 4T1 breast cancer cells in vitamin C-deficient mice | A Tale of Two Medicines | Scoop.it
Degradation of the extracellular matrix (ECM) plays a critical role in the formation of tumors and metastasis and has been found to correlate with the aggressiveness of tumor growth and invasiveness of cancer. Ascorbic acid, which is known to be essential for the structural integrity of the intercellular matrix, is not produced by humans and must be obtained from the diet. Cancer patients have been shown to have very low reserves of ascorbic acid. Our main objective was to determine the effect of ascorbate supplementation on metastasis, tumor growth and tumor immunohistochemistry in mice unable to synthesize ascorbic acid [gulonolactone oxidase (gulo) knockout (KO)] when challenged with B16FO melanoma or 4T1 breast cancer cells. Gulo KO female mice 36-38 weeks of age were deprived of or maintained on ascorbate in food and water for 4 weeks prior to and 2 weeks post intraperitoneal (IP) injection of 5×105 B16FO murine melanoma cells or to injection of 5×105 4T1 breast cancer cells into the mammary pad of mice. Ascorbate-supplemented gulo KO mice injected with B16FO melanoma cells demonstrated significant reduction (by 71%, p=0.005) in tumor metastasis compared to gulo KO mice on the control diet. The mean tumor weight in ascorbate supplemented mice injected with 4T1 cells was reduced by 28% compared to tumor weight in scorbutic mice. Scorbutic tumors demonstrated large dark cores, associated with increased necrotic areas and breaches to the tumor surface, apoptosis and matrix metalloproteinase-9 (MMP-9), and weak, disorganized or missing collagen I tumor capsule. In contrast, the ascorbate-supplemented group tumors had smaller fainter colored cores and confined areas of necrosis/apoptosis with no breaches from the core to the outside of the tumor and a robust collagen I tumor capsule. In both studies, ascorbate supplementation of gulo KO mice resulted in profoundly decreased serum inflammatory cytokine interleukin (IL)-6 (99% decrease, p=0.01 in the B16F0 study and 85% decrease, p=0.08 in the 4T1 study) compared to the levels in gulo KO mice deprived of ascorbate. In the B16FO study, ascorbate supplementation of gulo KO mice resulted in profoundly decreased serum VEGF (98% decrease, p=0.019 than in the scorbutic gulo KO mice). As expected, mean serum ascorbate level in ascorbate-restricted mice was 2% (p<0.001) of the mean ascorbate levels in supplemented mice. In conclusion, ascorbate supplementation hinders metastasis, tumor growth and inflammatory cytokine secretion as well as enhanced encapsulation of tumors elicited by melanoma and breast cancer cell challenge in gulo KO mice.
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ABC Says Echinacea Preparation as Effective as Tamiflu® in Early Flu Cases in Large Clinical Trial

ABC Says Echinacea Preparation as Effective as Tamiflu® in Early Flu Cases in Large Clinical Trial | A Tale of Two Medicines | Scoop.it
New clinical research suggests that an herbal medicinal product containing a proprietary combination of a concentrated echinacea herb and root extract is as effective as the conventional antiviral medicine oseltamivir (Tamiflu®) in the early treatment of influenza. The results of the randomized, double-blind, controlled clinical trial were published online in April in the open-access journal Current Therapeutic Research. [1]

For the study, researchers recruited 473 patients who had exhibited flu symptoms for less than 48 hours from 29 primary care practices in the Czech Republic. The patients were randomly assigned to take Echinaforce® Hotdrink syrup, a beverage containing an alcoholic extract prepared from freshly harvested echinacea (Echinacea purpurea) herb and root (95% herb; 5% root) supplemented with European elderberry (Sambucus nigra), for 10 days, or oseltamivir for five days followed by placebo for five days. (Echinaforce Hotdrink is produced and marketed by A. Vogel Bioforce AG of Roggwil, Switzerland. It is not currently sold in the United States.)

The primary endpoint of the clinical trial was the percentage of patients with mild or no symptoms after one, five, and 10 days of treatment. At each time point, the researchers found that a similar number of patients had recovered in both groups. After day one, 1.5% of patients in the Echinaforce Hotdrink group and 4.1% of those in the oseltamivir group exhibited mild or no symptoms; recovery rates for days five and 10 were 50.2% and 48.8%, and 90.1% and 84.8%, respectively.
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Stabilisation of Laryngeal AL Amyloidosis with Long Term Curcumin Therapy

Multiple myeloma (MM), smoldering myeloma (SMM), and monoclonal gammopathy of undetermined significance (MGUS) represent a spectrum of plasma cell dyscrasias (PCDs). Immunoglobulin light chain amyloidosis (AL) falls within the spectrum of these diseases and has a mortality rate of more than 80% within 2 years of diagnosis. Curcumin, derived from turmeric, has been shown to have a clinical benefit in some patients with PCDs. In addition to a clinical benefit in these patients, curcumin has been found to have a strong affinity for fibrillar amyloid proteins. We thus administered curcumin to a patient with laryngeal amyloidosis and smoldering myeloma and found that the patient has shown a lack of progression of his disease for a period of five years. This is in keeping with our previous findings of clinical benefits of curcumin in patients with plasma cell dyscrasias. We recommend further evaluation of curcumin in patients with primary AL amyloidosis.

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Dietary γ-Tocopherol Rich Mixture Inhibits Estrogen-Induced Mammary Tumorigenesis by Modulating Estrogen Metabolism, Antioxidant Response and PPARγ.

Dietary γ-Tocopherol Rich Mixture Inhibits Estrogen-Induced Mammary Tumorigenesis by Modulating Estrogen Metabolism, Antioxidant Response and PPARγ. | A Tale of Two Medicines | Scoop.it
This study evaluated the anti-cancer activity and mechanism of action of a γ-tocopherol rich tocopherol mixture, γ-TmT, in two different animal models of estrogen-induced breast cancer. The chemopreventive effect of γ-TmT at early (6 weeks), intermediate (18 weeks) and late (31 weeks) stages of mammary tumorigenesis was determined using the ACI rat model. Female rats receiving 17β-estradiol (E2) implants were administered with different doses (0, 0.05%, 0.1%, 0.3% and 0.5%) of γ-TmT diet. Treatment with 0.3% and 0.5% γ-TmT decreased tumor volume and multiplicity. At 31 weeks, serum concentrations of E2 were significantly decreased by γ-TmT. γ-TmT preferentially induced expression of the E2 metabolizing enzyme CYP1A1, over CYP1B1 in the rat mammary tissues. Nrf2-dependent antioxidant response was stimulated by γ-TmT, as evident from enhanced expression of its downstream targets, NQO1, GCLM and HMOX1. Serum concentrations of the oxidative stress marker, 8-isoprostane, were also decreased in the γ-TmT treated groups. Treatment with γ-TmT increased expression of PPARγ and its downstream genes, PTEN and p27, while the cell proliferation marker, PCNA, was significantly reduced in γ-TmT treated mammary tumors. In an orthotopic model in which human MCF-7 breast cancer cells were injected into the mammary fat pad of immunodeficient mice, γ-TmT inhibited E2-dependent tumor growth at all the doses tested. In conclusion, γ-TmT reduced mammary tumor development, in part through decreased E2 availability and reduced oxidative stress in mammary tissues; γ-TmT could thus be an effective agent for the prevention and treatment of E2-induced breast cancer.
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Curcumin reverses cisplatin resistance in cisplatin-resistant lung caner cells by inhibiting FA/BRCA pathway.

Curcumin reverses cisplatin resistance in cisplatin-resistant lung caner cells by inhibiting FA/BRCA pathway. | A Tale of Two Medicines | Scoop.it
Cisplatin (DDP) is the most widely used chemotherapy agent for treatment of malignancies including lung cancer. However, the effectiveness of DDP is often weakened by acquired resistance of tumor cells. DDP kills cancer cells primarily by creating intrastrand and interstrand DNA cross-links, which block DNA replication. The Fanconi anemia (FA)/BRCA pathway is a DNA cross-link damage repair pathway, which regulates cellular resistance to DNA cross-link agents, such as DDP. Some study has shown that natural compound curcumin sensitize human ovarian and breast cancer cells to DDP. However, whether curcumin may reverse resistance to DDP in DDP-resistant lung cancer cells has not been understood. In this study, we showed that curcumin enhanced the proliferation inhibitory effect of DDP and promote DDP-induced apoptosis in A549/DDP cells (DDP-resistant lung adenocarcinoma cells). Moreover, we observed that FA/BRCA pathway DNA damage repair processes, such as DDP-induced FANCD2 monoubiquitination and nuclear foci formation were downregulated in the presence of curcumin, suggesting that curcumin enhanced sensitivity to DDP in A549/DDP cells through the inhibition of FA/BRCA pathway. Furthermore, the calculation of q value and apoptosis analyses revealed that curcumin in combination with DDP could exert a synergistic cytotoxic effect in A549/DDP cells, further demonstrating that curcumin can reverse cisplatin resistance of A549/DDP cells. In conclusion, by suppressing the FA/BRCA pathway DNA repair, curcumin potentiates DDP-induced proliferation inhibitory effect and apoptosis in A549/DDP cell, indicating that curcumin may serve as a chemosensitizer to cross-link-inducing anticancer drugs DDP.
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Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity

Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity | A Tale of Two Medicines | Scoop.it
Resveratrol (RES) and curcumin (CUR) are polyphenols that are found in fruits and turmeric, and possess medicinal properties that are beneficial in various diseases, such as heart disease, cancer, and type 2 diabetes mellitus (T2DM). Results from recent studies have indicated that their therapeutic properties can be attributed to their anti-inflammatory effects. Owing to reports stating that they protect against β-cell dysfunction, we studied their mechanism(s) of action in β-cells. In T2DM, cAMP plays a critical role in glucose- and incretin-stimulated insulin secretion as well as overall pancreatic β-cell health. A potential therapeutic target in the management of T2DM lies in regulating the activity of phosphodiesterases (PDEs), which degrade cAMP. Both RES and CUR have been reported to act as PDE inhibitors in various cell types, but it remains unknown if they do so in pancreatic β-cells. In our current study, we found that both RES (0.1–10 μmol/l) and CUR (1–100 pmol/l)-regulated insulin secretion under glucose-stimulated conditions. Additionally, treating β-cell lines and human islets with these polyphenols led to increased intracellular cAMP levels in a manner similar to 3-isobutyl-1-methylxanthine, a classic PDE inhibitor. When we investigated the effects of RES and CUR on PDEs, we found that treatment significantly downregulated the mRNA expression of most of the 11 PDE isozymes, including PDE3B, PDE8A, and PDE10A, which have been linked previously to regulation of insulin secretion in islets. Furthermore, RES and CUR inhibited PDE activity in a dose-dependent manner in β-cell lines and human islets. Collectively, we demonstrate a novel role for natural-occurring polyphenols as PDE inhibitors that enhance pancreatic β-cell function.
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Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults

Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults | A Tale of Two Medicines | Scoop.it
At baseline of the randomization process, we proved the balance between the groups to be approximate equality in terms of patient demographics and clinical variables. None of the patients’ characteristics violated this, so equality was assumed in all aspects. The strength of our study lies in the comparison between the experimental and control groups at the end point of the study. As far as we are aware, no previous studies have been interested in evaluating comparisons of the clinical efficacy of vitamin C, while the majority have been interested in within-group before and after tests only. Our results indicate a clear effect of 1 g of vitamin C in alleviating inflammatory markers (hs-CRP and IL-6) among hypertensive and/or diabetic obese adults. Also, vitamin C strongly affected the level of FBG, significantly reducing it after 8 weeks of daily intake. For the lipid-profile variables TC and TG, our results are consistent with those of Afkhami-Ardekani and Shojaoddiny-Ardekani38 who found a positive effect of vitamin C on TG but no effect on TC.

We found that a moderate amount of vitamin C can significantly treat and reduce the inflammation, as measured by hs-CRP and IL-6, in hypertensive and/or diabetic adults and also helps to reduce FBG levels. Additional studies of different durations are needed to further explore the role of vitamin C in the lipid profile.
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Dose-response associations between cycling activity and risk of hypertension in regular cyclists: The UK Cycling for Health Study

Dose-response associations between cycling activity and risk of hypertension in regular cyclists: The UK Cycling for Health Study | A Tale of Two Medicines | Scoop.it
Most population studies on physical activity and health have involved largely inactive men and women, thus making it difficult to infer if health benefits occur at exercise levels above the current minimum guidelines. The aim was to examine associations between cycling volume and classical cardiovascular risk markers, including hypertension and hypercholesterolemia, in a population sample of habitual cyclists. A nationwide sample comprising 6949 men and women (aged 47.6 years on average) completed questions about their cycling levels, demographics and health. Nearly the entire sample (96.3%) achieved the current minimum physical activity recommendation through cycling alone. There was a dose–response association between cycling volume and risk of diagnosed hypertension (P-trend =0.001), with odds ratios of 0.98 (95% confidence interval (CI), 0.80–1.21), 0.86 (0.70, 1.06), 0.67 (95% CI, 0.53–0.83) across categories of 23–40, 40–61 and >61 metabolic equivalent hours/week (MET-h/week) compared with <23 MET-h/week. These associations persisted in models adjusted for age, sex, smoking, alcohol, body mass index (BMI) and other moderatevigorous physical activities. We also observed inverse associations between cycling volume and other risk factors including BMI and hypercholesterolemia. In summary, results from a population sample of cyclists suggest that additional cardiovascular health benefits can be achieved beyond the current minimum physical activity recommendation.
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Curcumin boosts DHA in the brain: Implications for the prevention of anxiety disorders.

Curcumin boosts DHA in the brain: Implications for the prevention of anxiety disorders. | A Tale of Two Medicines | Scoop.it
Dietary deficiency of docosahexaenoic acid (C22:6 n-3; DHA) is linked to the neuropathology of several cognitive disorders, including anxiety. DHA, which is essential for brain development and protection, is primarily obtained through the diet or synthesized from dietary precursors, however the conversion efficiency is low. Curcumin (diferuloylmethane), which is a principal component of the spice turmeric, complements the action of DHA in the brain, and this study was performed to determine molecular mechanisms involved. We report that curcumin enhances the synthesis of DHA from its precursor, α-linolenic acid (C18:3 n-3; ALA) and elevates levels of enzymes involved in the synthesis of DHA such as FADS2 and elongase 2 in both liver and brain tissues. Furthermore, in vivo treatment with curcumin and ALA reduced anxiety-like behavior in rodents. Taken together, these data suggest that curcumin enhances DHA synthesis, resulting in elevated brain DHA content. These findings have important implications for human health and the prevention of cognitive disease, particularly for populations eating a plant-based diet or who do not consume fish, a primary source of DHA, since DHA is essential for brain function and its deficiency is implicated in many types of neurological disorders.
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Water fluoridation for the prevention of dental caries.

Water fluoridation for the prevention of dental caries. | A Tale of Two Medicines | Scoop.it

Dental caries is a major public health problem in most industrialised countries, affecting 60% to 90% of school children. Community water fluoridation was initiated in the USA in 1945 and is currently practised in about 25 countries around the world; health authorities consider it to be a key strategy for preventing dental caries. Given the continued interest in this topic from health professionals, policy makers and the public, it is important to update and maintain a systematic review that reflects contemporary evidence.

To evaluate the effects of water fluoridation (artificial or natural) on the prevention of dental caries.To evaluate the effects of water fluoridation (artificial or natural) on dental fluorosis.

We searched the following electronic databases: The Cochrane Oral Health Group's Trials Register (to 19 February 2015); The Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2015); MEDLINE via OVID (1946 to 19 February 2015); EMBASE via OVID (1980 to 19 February 2015); Proquest (to 19 February 2015); Web of Science Conference Proceedings (1990 to 19 February 2015); ZETOC Conference Proceedings (1993 to 19 February 2015). We searched the US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization's WHO International Clinical Trials Registry Platform for ongoing trials. There were no restrictions on language of publication or publication status in the searches of the electronic databases.

For caries data, we included only prospective studies with a concurrent control that compared at least two populations - one receiving fluoridated water and the other non-fluoridated water - with outcome(s) evaluated at at least two points in time. For the assessment of fluorosis, we included any type of study design, with concurrent control, that compared populations exposed to different water fluoride concentrations. We included populations of all ages that received fluoridated water (naturally or artificially fluoridated) or non-fluoridated water.

We used an adaptation of the Cochrane 'Risk of bias' tool to assess risk of bias in the included studies.We included the following caries indices in the analyses: decayed, missing and filled teeth (dmft (deciduous dentition) and DMFT (permanent dentition)), and proportion caries free in both dentitions. For dmft and DMFT analyses we calculated the difference in mean change scores between the fluoridated and control groups. For the proportion caries free we calculated the difference in the proportion caries free between the fluoridated and control groups.For fluorosis data we calculated the log odds and presented them as probabilities for interpretation.

A total of 155 studies met the inclusion criteria; 107 studies provided sufficient data for quantitative synthesis.The results from the caries severity data indicate that the initiation of water fluoridation results in reductions in dmft of 1.81 (95% CI 1.31 to 2.31; 9 studies at high risk of bias, 44,268 participants) and in DMFT of 1.16 (95% CI 0.72 to 1.61; 10 studies at high risk of bias, 78,764 participants). This translates to a 35% reduction in dmft and a 26% reduction in DMFT compared to the median control group mean values. There were also increases in the percentage of caries free children of 15% (95% CI 11% to 19%; 10 studies, 39,966 participants) in deciduous dentition and 14% (95% CI 5% to 23%; 8 studies, 53,538 participants) in permanent dentition. The majority of studies (71%) were conducted prior to 1975 and the widespread introduction of the use of fluoride toothpaste.There is insufficient information to determine whether initiation of a water fluoridation programme results in a change in disparities in caries across socioeconomic status (SES) levels.There is insufficient information to determine the effect of stopping water fluoridation programmes on caries levels.No studies that aimed to determine the effectiveness of water fluoridation for preventing caries in adults met the review's inclusion criteria.With regard to dental fluorosis, we estimated that for a fluoride level of 0.7 ppm the percentage of participants with fluorosis of aesthetic concern was approximately 12% (95% CI 8% to 17%; 40 studies, 59,630 participants). This increases to 40% (95% CI 35% to 44%) when considering fluorosis of any level (detected under highly controlled, clinical conditions; 90 studies, 180,530 participants). Over 97% of the studies were at high risk of bias and there was substantial between-study variation.

There is very little contemporary evidence, meeting the review's inclusion criteria, that has evaluated the effectiveness of water fluoridation for the prevention of caries.The available data come predominantly from studies conducted prior to 1975, and indicate that water fluoridation is effective at reducing caries levels in both deciduous and permanent dentition in children. Our confidence in the size of the effect estimates is limited by the observational nature of the study designs, the high risk of bias within the studies and, importantly, the applicability of the evidence to current lifestyles. The decision to implement a water fluoridation programme relies upon an understanding of the population's oral health behaviour (e.g. use of fluoride toothpaste), the availability and uptake of other caries prevention strategies, their diet and consumption of tap water and the movement/migration of the population. There is insufficient evidence to determine whether water fluoridation results in a change in disparities in caries levels across SES. We did not identify any evidence, meeting the review's inclusion criteria, to determine the effectiveness of water fluoridation for preventing caries in adults.There is insufficient information to determine the effect on caries levels of stopping water fluoridation programmes.There is a significant association between dental fluorosis (of aesthetic concern or all levels of dental fluorosis) and fluoride level. The evidence is limited due to high risk of bias within the studies and substantial between-study variation.

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Protective effects of dietary avocado oil on impaired electron transport chain function and exacerbated oxidative stress in liver mitochondria from diabetic rats.

Protective effects of dietary avocado oil on impaired electron transport chain function and exacerbated oxidative stress in liver mitochondria from diabetic rats. | A Tale of Two Medicines | Scoop.it
Electron transport chain (ETC) dysfunction, excessive ROS generation and lipid peroxidation are hallmarks of mitochondrial injury in the diabetic liver, with these alterations also playing a role in the development of non-alcoholic fatty liver disease (NAFLD). Enhanced mitochondrial sensitivity to lipid peroxidation during diabetes has been also associated to augmented content of C22:6 in membrane phospholipids. Thus, we aimed to test whether avocado oil, a rich source of C18:1 and antioxidants, attenuates the deleterious effects of diabetes on oxidative status of liver mitochondria by decreasing unsaturation of acyl chains of membrane lipids and/or by improving ETC functionality and decreasing ROS generation. Streptozocin-induced diabetes elicited a noticeable increase in the content of C22:6, leading to augmented mitochondrial peroxidizability index and higher levels of lipid peroxidation. Mitochondrial respiration and complex I activity were impaired in diabetic rats with a concomitant increase in ROS generation using a complex I substrate. This was associated to a more oxidized state of glutathione, All these alterations were prevented by avocado oil except by the changes in mitochondrial fatty acid composition. Avocado oil did not prevented hyperglycemia and polyphagia although did normalized hyperlipidemia. Neither diabetes nor avocado oil induced steatosis. These results suggest that avocado oil improves mitochondrial ETC function by attenuating the deleterious effects of oxidative stress in the liver of diabetic rats independently of a hypoglycemic effect or by modifying the fatty acid composition of mitochondrial membranes. These findings might have also significant implications in the progression of NAFLD in experimental models of steatosis.
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Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model

Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model | A Tale of Two Medicines | Scoop.it
Electronic cigarettes (E-cigs) have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated. Presently, we determined that E-cig vapor contains 7x1011 free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, we developed an inhalation chamber for E-cig exposure. Mice that were exposed to E-cig vapor contained serum cotinine concentrations that are comparable to human E-cig users. E-cig exposure for 2 weeks produced a significant increase in oxidative stress and moderate macrophage-mediated inflammation. Since, COPD patients are susceptible to bacterial and viral infections, we tested effects of E-cigs on immune response. Mice that were exposed to E-cig vapor showed significantly impaired pulmonary bacterial clearance, compared to air-exposed mice, following an intranasal infection with Streptococcus pneumonia. This defective bacterial clearance was partially due to reduced phagocytosis by alveolar macrophages from E-cig exposed mice. In response to Influenza A virus infection, E-cig exposed mice displayed increased lung viral titers and enhanced virus-induced illness and mortality. In summary, this study reports a murine model of E-cig exposure and demonstrates that E-cig exposure elicits impaired pulmonary anti-microbial defenses. Hence, E-cig exposure as an alternative to cigarette smoking must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections.
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High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice

High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice | A Tale of Two Medicines | Scoop.it
Blood–brain barrier (BBB) breakdown and mitochondrial dysfunction have been implicated in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. Besides vitamin C being as one of the important antioxidants, recently, it has also been reported as a modulator of BBB integrity and mitochondria morphology. Plasma levels of vitamin C are decreased in AD patients, which can affect disease progression. However, investigation using animal models on the role of vitamin C in the AD pathogenesis has been hampered because rodents produce with no dependence on external supply. Therefore, to identify the pathogenic importance of vitamin C in an AD mouse model, we cross-bred 5 familial Alzheimer's disease mutation (5XFAD) mice (AD mouse model) with ι-gulono-γ-lactone oxidase (Gulo) knockout (KO) mice, which are unable to synthesize their own vitamin C, and produced Gulo KO mice with 5XFAD mice background (KO-Tg). These mice were maintained on either low (0.66 g/l) or high (3.3 g/l) supplementation of vitamin C. We found that the higher supplementation of vitamin C had reduced amyloid plaque burden in the cortex and hippocampus in KO-Tg mice, resulting in amelioration of BBB disruption and mitochondrial alteration. These results suggest that intake of a larger amount of vitamin C could be protective against AD-like pathologies.
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The Remedial Efficacy of Spirulina platensis versus Chromium-Induced Nephrotoxicity in Male Sprague-Dawley Rats

The Remedial Efficacy of Spirulina platensis versus Chromium-Induced Nephrotoxicity in Male Sprague-Dawley Rats | A Tale of Two Medicines | Scoop.it
This study was conducted to investigate the possible protective effect of Spirulina platensis against chromium-induced nephrotoxicity. A total of 36 adult male Sprague-Dawley rats were divided into 4 equal groups (Gps). Gp1 served as control, rats of Gps 2, 3, and 4 were exposed to Spirulina platensis (300 mg/kg b.wt per os) and sodium dichromate dihydrate (SDD) via drinking water at concentration of 520 mg /l respectively. Chromium administration caused alterations in the renal function markers as evidenced by significant increase of blood urea and creatinine levels accompanied with significant increase in kidney’s chromium residues and MDA level as well as decreased catalase activity and glutathion content in kidney tissue. Histologically, Cr provoked deleterious changes including: vascular congestion, wide spread tubular epithelium necrobiotic changes, atrophy of glomerular tuft and proliferative hyperplasia. The latter was accompanied with positive PCNA expression in kidney tissues as well as DNA ploidy interpretation of major cellular population of degenerated cells, appearance of tetraploid cells, high proliferation index and high DNA index. Morphometrical measurements revealed marked glomerular and tubular lumen alterations. On contrary, spirulina co-treatment with Cr significantly restored the histopathological changes, antioxidants and renal function markers and all the previously mentioned changes as well.
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