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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
July 7, 2012

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Standard vs. Customized Approaches to Weight Loss
Changing Epidemiology of S. aureus Infections in the U.S.
Seasonality, Suicide, Serotonin, and SSRIs
Averting Postpartum Depression in Women at Risk
Does Metformin Reduce Risk for Breast Cancer?
Dark Chocolate Might Lower CV Risk in People with Metabolic Syndrome
Defining Optimal Serum 25-Hydroxyvitamin D Concentration
After Bariatric Surgery, Patients Face Increased Risk for Alcohol Use Disorders
Curry Spice + Omega-3 Curbed Spine Injuries in Rats
NSAIDs Protect Against Skin Cancer

MM: A high drop-out rate. Nominal weight loss. Substantial complete weight re-gain (recidivism) and high cost per pound ($50-100/lb). All of these factors are common in virtually every weight loss program. HCG has a lower cost per pound (about $20). A lower recidivism rate (less than 30%). A very low drop-out rate (less than 5%) and substantial weight loss (average 25 lbs in the initial cycle). All of these characteristics are common in HCG Metabolic Syndrome Management Patients. Yet, many clinicians are still resistant to its use with the unfounded claim that it may be dangerous to lose a large amount of weight in a short amount of time. If we add the metabolic benefits of decreased blood pressure, decreased cholesterol, reversal of pre-diabetic conditions and lessening of diabetic conditions coupled with the advantages of chronic pain relief, diminished menopausal vasomotor symptoms and enhanced libido in many patients, it makes it hard to believe that there would be any resistance to this protocol.
JAMA 2012 Jun 27; 307:2617
Standard vs. Customized Approaches to Weight Loss
A standard approach was slightly more effective, but the customized approach was less expensive.
Many approaches to weight loss have been proposed. In this study, 363 adults (mostly women; mean age, 42; mean body-mass index, 33 kg/m2) received up to 42 group-based counseling sessions over 18 months that included typical knowledge-based approaches to physical activity promotion and eating behaviors. Participants were randomized to either a standard behavioral weight loss intervention group (SBWI; participants received the full fixed set of counseling sessions) or to a stepped care group (STEP; the frequency and type of sessions were modified depending on the achievement of specific goals every 3 months). STEP participants moved to the next set of counseling sessions only if the prior goal was not achieved.
About 72% of each group completed the full 18-month program. At 18 months, mean weight loss was 7.6 kg in the SBWI group and 6.2 kg in the STEP group (8.1% vs. 6.9%, a nonsignificant difference). The total cost was estimated to be about US$1350 for the SBWI and $780 for the STEP program.
Comment: These approaches suffer from all the same problems as other behavioral approaches: a fairly modest weight loss for so much effort, a partial rebound in weight loss from the initial response (weight loss in both groups peaked at 6 months), and a significant drop-out rate. The wide variation in costs argues for an approach that focuses more energy on patients who are making less progress, rather than a one-size-fits-all approach.
Thomas L. Schwenk, MD Published in Journal Watch General Medicine July 5, 2012
Citation(s): Jakicic JM et al. Effect of a stepped-care intervention approach on weight loss in adults: A randomized clinical trial. JAMA 2012 Jun 27; 307:2617.
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MM: Finally, some good news! At least it is, on the surface. MRSA infections seem to be on the downswing. This could be due to our bodies developing a resistance or tolerance to the bug or it could be faulty sampling in the study. Whichever it is, we must not become overconfident thet MRSA has simply gone away. Remember, it is better to strengthen the immune system so that it may adapt to challenges than to rely solely on antibiotics. Ultimately, bugs are smarter/more adaptive that antibiotics and will prevail.
JAMA 2012 Jul 4; 308:50
Changing Epidemiology of S. aureus Infections in the U.S.
Data from the U.S. Military Health System from 2005 through 2010 suggest a declining incidence of MRSA infections.
The emergence of the USA300 strain as an important cause of community-onset methicillin-resistant Staphylococcus aureus (MRSA) infections in the late 1990s and early 2000s profoundly changed the epidemiology of staphylococcal disease, both in the U.S. and worldwide. Although several recent studies have suggested that the incidence of healthcare-associated and hospital-onset MRSA infections may be decreasing, less is known about rates of community-onset S. aureus infections. Investigators recently took advantage of the U.S. Military Health System's integrated electronic health records to assess the epidemiology of S. aureus infections from 2005 through 2010 for all individuals eligible to receive care through this network, including active duty members and reservists, retirees, and their family members.
The study period included >56 million person-years of observation. A total of 2643 blood and 80,281 wound or abscess annual first-positive S. aureus cultures were included in the analyses, with MRSA representing 42% of blood and 58% of wound or abscess S. aureus isolates. Unadjusted rates of community-onset S. aureus bacteremias — both MRSA and methicillin-susceptible (MSSA) — decreased significantly during the study period, as did rates of hospital-onset MRSA bacteremia and skin and soft-tissue infections (SSTIs). No significant overall change was seen in the incidence of community-onset MRSA or MSSA SSTIs; however, the proportion of community-onset SSTIs caused by MRSA decreased significantly beginning in 2007.
Comment: This study has the advantages of immense size and broad geographic representation, although some populations at high risk for staphylococcal disease (including injection-drug users and individuals with end-stage renal disease) are underrepresented. The results raise the question of whether immunity to staphylococcal disease has increased in the general population in the U.S., circulating strains of S. aureus have changed, or both.
Richard T. Ellison III, MD Published in Journal Watch Infectious Diseases July 3, 2012
Citation(s): Landrum ML et al. Epidemiology of Staphylococcus aureus blood and skin and soft tissue infections in the US Military Health System, 2005-2010. JAMA 2012 Jul 4; 308:50.
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MM: A wonderful way to improve serotonin balance is simple exposure to full spectrum sunlight. People with Seasonal Affected Disorder (SAD) almost invariably see mood and depression enhancement with anywhere from 20 minutes to several hours daily full spectrum sunlight. Simply moving near a sunny window or placing a full spectrum light bulb in your office or desk lamp may help. Sometimes the simple answers or activities can be the best.
Acta Psychiatr Scand 2012 Jun 8
Seasonality, Suicide, Serotonin, and SSRIs
Suicide peaks seasonally in men, even more so among those taking selective serotonin reuptake inhibitors.
Findings that suicide rates peak in spring and early summer (JW Psychiatry Jun 7 2010) have been partly attributed to a "circannual" pattern of serotonergic neurotransmission; several serotonin-related measures vary systematically throughout the year. Using 1992–2003 data from Swedish registries covering 12,448 suicides (72% men), researchers investigated whether different classes of antidepressants would alter the amplitude of this seasonal effect.
Use of selective serotonin reuptake inhibitors (SSRIs) was found in 9% of men and 15% of women; other antidepressant use in 8% and 14%, respectively; violent methods of suicide in 74% and 56%, respectively; and inpatient treatment during the 5 years before suicide in 33% and 50%, respectively. Among women, some trends but no statistically significant associations for month of suicide were found. Suicide risk in June compared with risk in December increased by 42% in men receiving SSRIs and by 12% in men receiving no antidepressants — a significant difference. Men using other antidepressants showed no seasonal patterns of suicide. Male SSRI users without inpatient hospitalizations showed the highest seasonal amplitude of suicide (relative risk, 1.56). Violent suicides tended to be more common among men taking SSRIs versus those taking no antidepressants.
Comment: SSRI-associated suicides by men in June were roughly double a previously reported increase in risk (≤20%) associated with springtime. Seasonality was not seen with other antidepressants, and suicide risks were higher for patients who hadn't been hospitalized, suggesting that these findings do not simply reflect higher suicides among treatment-refractory patients. After considering several hypotheses, the authors wonder whether SSRIs have additive effects on endogenous serotonin variations that accentuate seasonal suicidality. Without reigniting undue alarm linking SSRIs to suicidality, these findings support the practice of clinicians carefully monitoring depressed patients when initiating SSRIs.
Joel Yager, MD Published in Journal Watch Psychiatry June 25, 2012
Citation(s): Makris GD et al. Suicide seasonality and antidepressants: A register-based study in Sweden. Acta Psychiatr Scand 2012 Jun 8; [e-pub ahead of print].
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MM: Counseling is a potentially valuable tool for PPD but alone it may not be sufficient. Over the past 2 decades we have seen the use of Bio-identical Progesterone be extremely beneficial to patients suffering from PPD. Topically, twice to thrice daily dosing of commercially available products may work for many women but higher prescription doses may be necessary. Buccal lozenges have been useful by incorporating the direct absorption similar to transdermal creams as well as the oral absorption calming aspect of metabolic by-products that are present when the progesterone is swallowed. Call Mark Drugs at 630-529-3400 for more information.
Obstet Gynecol 2012 May; 119:942
Averting Postpartum Depression in Women at Risk
An educational intervention delivered to postpartum Latina and black women decreased the likelihood of positive depression screens.
Postpartum depression is a common disorder with ramifications for mothers, infants, and families; racial and ethnic minorities of low socioeconomic status are at particular risk. With input from mothers and community members, investigators at a tertiary inner-city hospital in East Harlem, New York, developed a postpartum educational intervention aimed at reducing the incidence of depression among black and Latina mothers. The intervention consisted of a short in-hospital session in which potential triggers of depressive symptoms (e.g., heavy vaginal bleeding, infant colic) were explained as normal, temporary aspects of the postpartum experience; specific suggestions for management also were provided. A follow-up phone call 2 weeks after discharge served to assess additional needs and activate referrals or symptom review when indicated. The efficacy of the intervention to reduce the incidence of positive depression screens at 3 weeks, 3 months, and 6 months postpartum was tested in a randomized controlled trial involving 540 participants.
Mothers who received the intervention were less likely to screen positive for depression at 3 weeks than those who did not (8.8% vs. 15.3%, P=0.03). The likelihood of a positive screen as late as 6 months postpartum was lower among treated women (odds ratio, 0.67). These findings persisted after adjustment for baseline depression.
Comment: The public health burden of postpartum depression is significant and is borne disproportionately by low-income women and women of color. That a relatively simple educational intervention can lower risk for postpartum depression is notable, particularly in an era when resources for managing mental health disorders in these communities can be scarce. The study highlights the value of better preparing women for the often-unfamiliar (but entirely normal) symptoms of the postpartum period. These investigators are to be applauded for including community members in the development of the intervention — an important consideration that is often overlooked in academic studies.
Allison Bryant, MD, MPH Published in Journal Watch Women's Health June 7, 2012
Citation(s): Howell EA et al. Reducing postpartum depressive symptoms among black and Latina mothers: A randomized controlled trial. Obstet Gynecol 2012 May; 119:942
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MM: Although an interesting piece of information, I am not ready to jump on this bandwagon just yet. Metformin has the effect of increasing the body’s sensitivity to the presence of insulin. Cancer cells also respond to insulin. Sometimes cancer cells react paradoxically in that they respond directly opposite to how “normal” cells are expected to react. This may be what modulates this statistical effect of metformin on cancer cells. In any case, more research is needed before any recommendations may be made.
J Clin Oncol 2012 Jun 11
Does Metformin Reduce Risk for Breast Cancer?
Patients with diabetes who received metformin had a lower risk for breast cancer than patients without diabetes.
Accumulating evidence suggests that metformin, a drug commonly used to treat patients with type 2 diabetes, might reduce the risk for developing breast cancer. Now, investigators have examined this possibility in postmenopausal women who participated in the Women's Health Initiative (WHI) trials.
The cohort of 68,019 women included 3401 patients with type 2 diabetes at study entry and excluded patients with type 1 diabetes. During a mean follow-up of 11.8 years, an additional 7889 received a diagnosis of diabetes, and 3273 received a diagnosis of invasive breast cancer.
Patients with diabetes who received medications other than metformin had a slightly higher risk for breast cancer than patients without diabetes (hazard ratio, 1.16; 95% confidence interval, 0.93–1.45). In contrast, patients with diabetes who received metformin had a lower risk for breast cancer than patients without diabetes (hazard ratio, 0.75; 95% CI, 0.57–0.99). The association between metformin use and lower incidence of breast cancer was restricted to tumors that were positive for estrogen receptor and progesterone receptor and negative for human epidermal growth factor receptor 2.
Comment: These results are provocative and supportive of some observational studies that have suggested a similar effect on breast cancer incidence among metformin users. The accompanying editorial carefully dissects the limitations of current and past studies on the topic. Numerous issues are important to consider, including imbalances in characteristics between patients with and without diabetes and evidence suggesting that women with diabetes might not receive mammograms or clinical evaluation as routinely as those without diabetes. Despite these and other caveats, an abundance of evidence suggests that insulin influences the development and progression of breast cancer, and numerous preclinical studies have shown that metformin interferes with important signaling pathways that might serve as drivers of tumor progression. Nevertheless, metformin should not be prescribed for reasons other than treatment of diabetes. Findings from the WHI study should inform the design of prevention and adjuvant therapy trials in patients with early-stage breast cancer.
William J. Gradishar, MD Published in Journal Watch Oncology and Hematology July 3, 2012
Citation(s): Chlebowski RT et al. Diabetes, metformin, and breast cancer in postmenopausal women. J Clin Oncol 2012 Jun 11; [e-pub ahead of print].
Goodwin PJ et al. Diabetes, metformin, and breast cancer: Lilac time? J Clin Oncol 2012 Jun 11; [e-pub ahead of print].
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MM: Our CoCo-Pro product offers a source of de-fatted Cocoa similar to the product used in this study. It is economical, very low calorie and delicious. We offer many ways to incorporate this product into your dietary regimen. Please call Mark Drugs at 630-529-3400 for more information or to order this product.
BMJ 2012 May 31; 344:e3657
Dark Chocolate Might Lower CV Risk in People with Metabolic Syndrome
In a statistical model, daily consumption of 100 g of dark chocolate lowered risks.
Dark chocolate is rich in polyphenols, including flavonoids, that have salutary cardiovascular (CV) and metabolic effects. Indeed, dark chocolate consumption lowers blood pressure and serum cholesterol levels. Using "best case scenario analysis," investigators modeled the long-term effects of daily dark chocolate consumption in patients at high risk for CV disease.
The modeled population consisted of 2000 people (mean age, 54) with metabolic syndrome and untreated hypertension, but without diabetes or CV disease. Risks for CV disease and death were calculated using established algorithms and registries. The effects of dark chocolate consumption (polyphenol content equivalent to 100 g of dark chocolate daily) were based on prior meta-analyses; the systolic blood pressure–lowering effect was assumed to be –5.0 mm Hg and the LDL cholesterol–lowering effect was assumed to be –8.1 mg/dL. Given these assumptions, 100% adherence with daily dark chocolate consumption would prevent 70 nonfatal and 15 fatal CV events per 10,000 persons during 10 years.
Comment: Because a beneficial effect of chocolate on CV events and mortality will never be proven by randomized trials, we must draw inferences from statistical models. This model, if correct, suggests that long-term, daily dark chocolate consumption would be a cost-effective and — according to the authors — "a pleasant, and hence sustainable" means of preventing adverse CV events in people with metabolic syndrome.
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine June 21, 2012
Citation(s): Zomer E et al. The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: Best case scenario analysis using a Markov model. BMJ 2012 May 31; 344:e3657.
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Ann Intern Med 2012 May 1; 156:627
Defining Optimal Serum 25-Hydroxyvitamin D Concentration
Low levels were associated with elevated risk for hip fracture, myocardial infarction, cancer, and death.
Low vitamin D levels are associated with adverse bone outcomes, and serum 25-hydroxyvitamin D (25[OH]D) deficiency is typically defined on the basis of its relation with bone metabolism. In this population-based, observational study, conducted in four U.S. communities, researchers evaluated the relation of 25(OH)D concentration and incidence of hip fracture, myocardial infarction (MI), cancer, and death. The primary outcome was a composite of all endpoints; levels were recorded across seasons.
The 1621 participants (mean age, 74) were followed for a median of 11 years. After adjustments for multiple covariates, people with season-specific 25(OH)D levels below the 29th percentile (approximately 20 ng/mL, or 50 nmol/L) had higher risk for the composite outcome (hazard ratio, 1.24) and death (HR, 1.32). The incidences of MI, cancer, and hip fracture were nonsignificantly elevated.
Comment: The Institute of Medicine (IOM) recommends a 25(OH)D target of 20 ng/mL, a cutoff that is substantially lower than that recommended by other organizations (JW Dermatol Dec 17 2010). In this observational study, researchers evaluated multiple outcomes (beyond bone health) and determined the optimal 25(OH)D level to be approximately the same as that recommended by the IOM. However, vitamin D levels are notoriously affected by clinical and demographic variables that make it difficult to discern cause-and-effect. Until randomized trials help us determine the optimal vitamin D level, it may be prudent to follow the IOM recommendation.
Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine June 21, 2012
Citation(s): de Boer IH et al. Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults: A cohort study. Ann Intern Med 2012 May 1; 156:627.
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MM: Increased sensitivity to alcohol or any drug may be an issue with aggressive weight loss irrespective of what the source is. Simply put, there is less body for the chemical to redistribute into so there is potentially more chemical in each body cell. Patients need to be aware of these potential changes in their bodies so that they can modify their activities at the very least.
After Bariatric Surgery, Patients Face Increased Risk for Alcohol Use Disorders
The risk for alcohol use disorders appears to be elevated in the second year after bariatric surgery, according to a JAMA study.
Some 2000 adults undergoing bariatric procedures completed an alcohol use assessment before surgery and at 1 and 2 years afterward. Overall, the prevalence of alcohol use disorders was significantly higher at year 2 (9.6%) than before surgery (7.6%) or at year 1 (7.3%). Most of the increased risk was seen with Roux-en-Y gastric bypass. Other independent predictors of risk included male sex, younger age, smoking, and alcohol dependence before surgery.
The researchers write: "It was likely an increase in alcohol sensitivity following [Roux-en-Y bypass] combined with resumption of higher levels of alcohol consumption in the second postoperative year" that led to the increase in alcohol use disorders. They conclude that patients should be counseled about this potentially increased risk, adding that "alcohol screening and, if indicated, referral should be offered as part of routine preoperative and postoperative clinical care."
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Curry Spice + Omega-3 Curbed Spine Injuries in Rats
Curry spice extract + omega-3 DHA preserved walking ability in rats with aging-driven spinal cord decline; omega-6 fats make matters worse
by Craig Weatherby

The exciting outcomes of a UCLA study support and expand on hopeful signs that began emerging several years ago.  
Earlier animal research from UCLA and the UK indicated that omega-3 DHA can blunt the effects of brain or spine injuries and enhance recovery. And in parallel research, the yellow pigment in turmeric (curcumin) – which also gives curry its characteristic sunny hue – had begun showing promise as a brain- and nerve-protector.

In addition to encouragement from the previous studies described below (see “New findings build on prior positive research”), the UCLA team had good reason to believe that these two common food factors could help protect spine health. Omega-3 DHA helps protect and repair damage to cell membranes, moderate and resolve inflammation, and promote production of chemicals that foster nerve growth and connections.

Curcumin displays strong anti-inflammatory effects, and has demonstrated considerable tissue-protection and -repair capacities. “The brain and spinal cord work together, and years of research demonstrates that supplements like DHA and curcumin can positively influence the brain,” said study co-author Fernando Gomez-Pinilla. Ph.D. “We suspected that what works in the brain may also work in the spinal cord.” (Schmidt E/UCLA 2012)

New findings build on prior positive research
Several years ago, we came across two studies regarding the potential for fishy omega-3 DHA and colorful curcumin to blunt the effects of brain damage. A team from the University of California at Los Angeles (UCLA) had reported that both curcumin and DHA – one of the two key omega-3s in fish fat – independently blunted the bad effects of brain injuries in rats (Wu A et al. 2004; Wu A et al. 2006). As we wrote in 2006, “… rats … that had been eating curcumin had much less oxidative damage to their brains, and it seemed to counteract the cognitive impairment caused by the conk on the head … [while] mice fed fish oil before being conked on the head enjoyed similar protection from the ill effects of head trauma.”  
(See “Turmeric Power, Part II: Curry Spice May Curb Alzheimer’s > http://vitalchoice.com/shop/pc/articlesView.asp?id=236 <” and scroll down to the section titled “Conked on the head? Eat fish, take turmeric”.)

Since then, evidence that DHA – the omega-3 that’s critical to brain/nerve development and functions – has continued to pile up … see “Miner’s Miracle Leads Stellar Omega-3 Summary”, “Fish Fat Curbed Rat's Brain Injuries”, “Sugary Brain Damage Blunted by Omega-3s”, “Omega-3 Curbed Traumatic Brain Injury in Rats”, and “Fish Fats Boost Brain Resilience”. Meanwhile, across the Atlantic, a group from Queen Mary University of London has been reporting remarkable recovery-enhancing effects in rodents given omega-3 DHA after a spine injury … orally, intravenously, and/or by injection (King VR et al. 2006; Michael-Titus AT 2007; Huang WL et al. 2007).

Last month, we were privileged to see Queen Mary University scientist Adina Michael-Titus, D.Sc., present the amazing results of her team’s research into the ability of omega-3 DHA to reduce the effects of spinal injuries and enhance recovery. In 2006, her team reported that omega-6 fats actually worsen outcomes of spinal injuries:
“This report shows a striking difference in efficacy between the effects of treatment with omega-3 and omega-6 PUFAs [fatty acids] on the outcome of SCI [spinal cord injury], with omega-3 PUFAs being neuroprotective and omega-6 PUFAs having a damaging effect.” (King VR et al. 2006). They also found that timing was critical … the sooner the animals got DHA, the stronger the protection from disability. And continued feeding of DHA during the following weeks enhanced the animals’ long-term recovery.

Now, the same UCLA team reports that a diet enriched with omega-3 DHA and curcumin markedly protected walking ability in rats given a common, aging-related form of spinal degeneration (Holly LT et al. 2012). Together, these two common food factors helped repair the animals’ nerve cells and preserve their neurological functions from the effects of degenerative damage to the neck.

Curcumin + omega-3 DHA protected spine-injured rats’ walking ability
The UCLA team compared healthy rats to two groups of rats that underwent surgery designed to induce a degenerative spinal disorder often seen in conditions like rheumatoid arthritis and osteoporosis.

The condition – called cervical spondylotic myelopathy (CSM) – can lead to disabling symptoms such as difficulty walking, neck and arm pain, hand numbness, and weakness of the limbs. It’s the most common cause of spine-related walking problems in people over 55. According to neurosurgeon and UCLA study leader Langston Holly, M.D., “Normal aging often narrows the spinal canal, putting pressure on the spinal cord and injuring tissue. While surgery can relieve the pressure and prevent further injury, it can't repair damage to the cells and nerve fibers. We wanted to explore whether dietary supplementation could help the spinal cord heal itself.” (Schmidt E/UCLA 2012)

The rats with simulated CSM were divided into two groups:

The researchers recorded the rats’ walking behavior while they were healthy. After the animals underwent an injury designed to simulate the effects of CSM, the UCLA team re-examined the animals’ gait on a weekly basis. As early as three weeks after simulated CSM was induced, the rats in Group 1 – who were eating a chow that mimicked the standard American diet – demonstrated measurable walking problems that worsened as the study progressed.

The rats in Group 2 – those fed a diet enriched with DHA and curcumin – walked significantly better than those in Group 1, even six weeks after the study's start.

Curcumin + omega-3 DHA also protected rats’ spinal nerve cells
Next, the scientists examined the injured rats’ spinal cords to see how the two differing diets might affect their injury on a molecular level. They measured levels of three markers respectively linked to cell-membrane damage, neural repair, and nerve-cell communication: 4-HNE, BDNF, and syntaxin-3. The rats that ate the standard American diet showed higher levels of the marker (4-HNE) linked to cell-membrane damage. In contrast, DHA and curcumin appeared to offset the injury’s effect, with the rats in Group 2 displaying damage-marker (4-HNE) levels equivalent to those seen in the control group. Levels of the markers linked to neural repair and cellular communication (BDNF and syntaxin-3) were significantly lower in the rats raised on the Western diet. In contrast, levels in the animals fed the DHA-curcumin supplemented diet appeared similar to those of the control group.

DHA and curcumin appear to invoke several molecular mechanisms that preserved neurological function in the rats,” said Gomez-Pinilla. “This is an exciting first step toward understanding the role that diet plays in protecting the body from degenerative disease.” (Schmidt E/UCLA 2012)  “Our findings suggest that diet can help minimize disease-related changes and repair damage to the spinal cord,” Holly said.” (Schmidt E/UCLA 2012)

Their research was supported by grants from the National Institutes of Health and the Craig H. Neilsen Foundation.

Sources: Bousquet M, Gibrat C, Saint-Pierre M, Julien C, Calon F, Cicchetti F. Modulation of brain-derived neurotrophic factor as a potential neuroprotective mechanism of action of omega-3 fatty acids in a parkinsonian animal model. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1401-8. Epub 2009 Jul 24. Calderon F, Kim HY. Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem. 2004;90(4):979-988. Holly LT, Blaskiewicz D, Wu A, Feng C, Ying Z, Gomez-Pinilla F. Dietary therapy to promote neuroprotection in chronic spinal cord injury. J Neurosurg Spine. 2012 Jun 26. [Epub ahead of print] Huang WL, King VR, Curran OE, Dyall SC, Ward RE, Lal N, Priestley JV, Michael-Titus AT. A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury. Brain. 2007 Nov;130(Pt 11):3004-19. Epub 2007 Sep 27. King VR, Huang WL, Dyall SC, Curran OE, Priestley JV, Michael-Titus AT. Omega-3 fatty acids improve recovery, whereas omega-6 fatty acids worsen outcome, after spinal cord injury in the adult rat. J Neurosci. 2006 Apr 26;26(17):4672-80. Kitamura T, Saitoh Y, Takeshima N, et al. Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell. 2009;139(4):814-827.  Logan AC. Omega-3 and BDNF regulation: eicosapentaenoic acid may play a key role in limitation of CNS injury. J Neurotrauma. 2008 Dec;25(12):1499. No abstract available. Michael-Titus AT. Omega-3 fatty acids and neurological injury. Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):295-300. Epub 2007 Nov 26. Review. Schmidt E. Curry spice, omega-3 fatty acid preserve walking ability following spinal-cord injury. University of California at Los Angeles (UCLA). June 26, 2012 Accessed at http://newsroom.ucla.edu/portal/ucla/ucla-study-shows-omega-3-fatty-235713.aspx. Wu A, Ying Z, Gomez-Pinilla F. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma. 2004;21(10):1457-1467. Wu A., Ying Z., Gomez-Pinilla F. Dietary curcumin counteracts the outcome of traumatic brain injury on oxidative stress, synaptic plasticity, and cognition. Exp Neurol. 2006 Feb;197(2):309-17. Epub 2005 Dec 20. Yarbrough CK, Murphy RK, Ray WZ, Stewart TJ. The natural history and clinical presentation of cervical spondylotic myelopathy. Adv Orthop. 2012;2012:480643. Epub 2011 Dec 22.
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Cancer 2012 May 29
NSAIDs Protect Against Skin Cancer
Compared with never-users, ever-users had reduced risk for SCCs, malignant melanomas, and certain BCCs.
Experimental models have shown procarcinogenic effects of cyclooxygenase (COX) enzymes, which promote inflammation, facilitate invasion through the basement membrane zone, suppress host antitumor defense mechanisms, inhibit tumor cell apoptosis, and stimulate angiogenesis. Nonsteroidal anti-inflammatory drugs (NSAIDs) block COX activity. These authors examined the association between NSAID use and risk for squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM) in patients with histologically verified cases recorded in the Danish cancer registry between 1991 and 2008. Patients with human immunodeficiency virus infection, organ transplants, or previous cancer diagnoses were excluded.
Overall, NSAID users had a reduction in SCC and MM, but not BCC, compared with those who had never taken NSAIDs. Reduction in risk was associated with duration of NSAID use and dose size. Among long-term, high-dose NSAID users, the risk reduction was 46% for MM, 35% for SCC, and 17% for BCC. The reduced risk for SCC and melanoma was irrespective of anatomic site, but only BCCs sited elsewhere than the head and neck were influenced by NSAID use. Both aspirin and nonselective NSAIDs effectively protected against SCC and MM; newer COX-2 inhibitors were associated with reductions in SCC but not MM. High-dose, long-term use of acetaminophen was associated with a reduced risk for MM and for BCCs other than on the head and neck.
Comment: This evidence confirms the findings of epidemiologic studies showing that nonsteroidal anti-inflammatory drugs protect against skin cancer and two interventional studies showing such an effect with COX-2 inhibitors. The costs and morbidity associated with surgical treatment of nonmelanoma skin cancer (NMSC) and melanoma pose a serious problem. These cancers are among the few with a rising incidence. The use of NSAIDs, many of which are inexpensive and available over-the-counter, for prevention of NMSC and melanoma is attractive, and could have major public health implications, but it is best to wait for more studies before we recommend them. Which NSAIDs are most effective and free of adverse effects and at what dosages is unknown.
Craig A. Elmets, MD Published in Journal Watch Dermatology June 22, 2012
Citation(s): Johannesdottir SA et al. Nonsteroidal anti-inflammatory drugs and the risk of skin cancer: A population-based case-control study. Cancer 2012 May 29; [e-pub ahead of print].

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