Cytokine and IDO metabolite changes effected by calcium pterin during inhibition of MDA-MB-231 xenograph tumors in nude mice

In vivo studies of the effectiveness of various forms of calcium pterin reveal significant antitumor activity associated with (1:4, mol/mol) calcium pterin (CaPterin), (1:2, mol/mol) calcium pterin, dipterinyl calcium pentahydrate (DCP), as well as unexpectedly for a calcium chloride dihydrate solution in nude mice with MDA-MB-231 xenographs. Stepwise regression analysis of nine plasma cytokine and indoleamine 2,3-dioxygenase (IDO) metabolite levels identified four effects correlated to (1:4, mol/mol) calcium pterin administration: (1) decreased IL-6, (2) increased IL-10, (3) decreased IFN-gamma, and (4) increased kynurenine. CONCLUSION: (1:4, mol/mol) CaPterin exerts significant (by Spearman rank order correlation) dose-response antitumor activity in nude mice with MDA-MB-231 xenographs, and sustains both inflammatory and anti-inflammatory changes in the levels of certain plasma factors.     

Anxiety-like behaviors produced by acute fluoxetine administration in male Fischer 344 rats are prevented by prior exercise

RATIONALE: Although selective 5-HT reuptake inhibitors (SSRIs) can reduce anxiety after chronic treatment, acute SSRI administration is associated with an increase in anxiety consistent with an acute increase in 5-HT neurotransmission. Exercise is anxiolytic in humans, and wheel running prevents anxiety-like behavioral consequences of uncontrollable stress in rats, but the effects of exercise on acute fluoxetine-induced anxiety-like behaviors are unknown. OBJECTIVES: The current studies tested the hypothesis that acute administration of the SSRI fluoxetine would produce behaviors in rats resembling those produced by uncontrollable stress and that these behaviors would be blocked by prior wheel running. RESULTS: Adult, male Fisher 344 rats administered moderate (10 mg/kg) or high (20 mg/kg) doses of fluoxetine demonstrated exaggerated shock-elicited freezing and an interference with shuttle box escape compared to rats given either saline or low-dose fluoxetine (2.5 mg/kg). Fluoxetine-induced behaviors were similar to, but smaller in magnitude than, those produced by uncontrollable stress and were blocked by pretreatment with the 5-HT(2C) receptor antagonist SB 242084 (1 mg/kg). Rats allowed access to running wheels for 6 weeks were protected against the anxiety-like behaviors produced by a single injection of fluoxetine (10 mg/kg). CONCLUSIONS: Behavioral effects of acute fluoxetine administration resemble those produced by uncontrollable stress. Results are consistent with the idea that exercise can produce resistance against the anxiogenic effects of acute increases in 5-HT and suggest that acute behavioral effects of antidepressants can depend on history of physical activity.     

Pyrroloacridine alkaloids from Plakortis quasiamphiaster: structures and bioactivity

A re-collection of Plakortis quasiamphiaster from Vanuatu in 2003 resulted in the isolation of three known compounds, plakinidine A (1) and amphiasterins B1 (6) and B2 (7). Also isolated was a new bis-oxygenated pyrroloacridine alkaloid, plakinidine E (8), with a unique O-substitution versus N-substitution at position C-12 in 1. The biological evaluation of the active compounds in two assays provided complementary data. Plakinidine A (1) exhibited cytotoxicity against human colon H-116 cells with an IC50 of 0.23 microg/mL, but there were no effects against the yeast Saccharomyces cerevisiae diploid homozygous deletion strain of topoisomerase I (top1Delta). By contrast, 8 was inactive against H-116 cells but was potent in the yeast halo screen.     

The Quality of Drinking Water in North Carolina Farmworker Camps

Objectives. The purpose of this study was to assess water quality in migrant farmworker camps in North Carolina and determine associations of water quality with migrant farmworker housing characteristics.Methods. We collected data from 181 farmworker camps in eastern North Carolina during the 2010 agricultural season. Water samples were tested using the Total Coliform Rule (TCR) and housing characteristics were assessed using North Carolina Department of Labor standards.Results. A total of 61 (34%) of 181 camps failed the TCR. Total coliform bacteria were found in all 61 camps, with Escherichia coli also being detected in 2. Water quality was not associated with farmworker housing characteristics or with access to registered public water supplies. Multiple official violations of water quality standards had been reported for the registered public water supplies.Conclusions. Water supplied to farmworker camps often does not comply with current standards and poses a great risk to the physical health of farmworkers and surrounding communities. Expansion of water monitoring to more camps and changes to the regulations such as testing during occupancy and stronger enforcement are needed to secure water safety.Water is the essence of human life, part of every cell and vital for every function of our body. The World Health Organization has declared access to a regular supply of safe water a basic human right which has to be respected, protected, and fulfilled.1 The consequences of failing to do so are alarming: diarrheal diseases causing 2 million annual deaths worldwide; outbreaks of cholera, legionella, and other waterborne pathogens; and cancer and tooth and skeletal damage because of unsafe levels of arsenic and fluoride.2 Developing countries carry the main burden of these diseases. However, provision of safe water is a global responsibility shared by individuals as well as local, state, and federal governments. For this purpose, international and local guidelines and regulations have been created to ensure drinking water quality.3–5Migrant farmworkers represent a particularly vulnerable population within the US for diseases resulting from unsafe drinking water, in conjunction with other environmental and occupational hazards.6 The large number of migrant farmworkers that labor in the United States has little control of their living environments, including the water available for drinking, bathing, and laundry.7 Although federal and state regulations have been developed to ensure adequate and safe housing for migrant farmworkers, the standards are often not met.8 The few studies published on water quality indicate that contamination of drinking water is a continuing concern.9 Although pesticides and nitrates contained in drinking water represent a recognized problem, this study focuses on fecal contamination of water.10 Total coliform were found in drinking water of half of 30 farmworker camps tested in North Carolina in 1989.11 A US Environmental Protection Agency (EPA) investigation into the drinking water quality of migrant camps in Wisconsin revealed that water in 67% of camps contained total coliform bacteria in 1997.12 Two of 5 farmworker camps located in Colorado were also tested positive for total coliform in 2002.13 Breaches in water safety are persistent and widespread.9This study describes the quality of drinking water and tests its association to housing characteristics and living conditions in 181 migrant farmworker camps located in eastern North Carolina during the 2010 agricultural season. The results are further compared with previously published data of water quality.11     

Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case-control study.

Dietary intake of tomatoes and tomato products containing lycopene, an antioxidant carotenoid, has been shown in recent studies to reduce the risk of cancer. This study was conducted to investigate the serum and prostate tissue lycopene and other major carotenoid concentrations in cancer patients and their controls. Serum lipid and protein oxidation was also measured. Twelve prostate cancer patients and 12 age-matched subjects were used in the study. Significantly lower serum and tissue lycopene levels (44%, p = 0.04; 78%, p = 0.050, respectively) were observed in the cancer patients than in their controls. Serum and tissue beta-carotene and other major carotenoids did not differ between the two groups (p = 0.395 and p = 0.280, respectively). Although there was no difference (p = 0.760) in serum lipid peroxidation between cancer patients and their controls (7.09 +/- 0.74 and 6.81 +/- 0.56 mumol/l, respectively), serum protein thiol levels were significantly lower among the cancer patients (p = 0.026). This study demonstrates that the status of lycopene but not other carotenoids in prostate cancer patients is different from controls. The role of dietary lycopene in preventing oxidative damage of biomolecules and thereby reducing the risk of prostate cancer needs to be evaluated in future studies.     

Analysis of adverse events after anthrax immunization in US Army medical personnel

A broad range of health effects in a cohort of 601 health care personnel, immunized with anthrax vaccine adsorbed (AVA) as a military occupational health requirement, were assessed to evaluate adverse events both qualitatively and quantitatively. Active surveillance showed that localized reactions were common and occurred more often in women than men. Five patients were reported to the Vaccine Adverse Event Reporting System, but only one event could be definitively attributed to immunization, a large localized reaction. Two separate cohort studies, one using nested data from a standardized health risk appraisal instrument and the other comparing rates of outpatient visits and hospitalizations, did not reveal significant differences between AVA-immunized and unimmunized individuals. Our findings suggest that AVA is relatively reactogenic but do not indicate serious adverse health effects due to immunization.     

Vitamin D supplementation and bone mineral density in early postmenopausal women

BACKGROUND: Increased vitamin D intake may preserve or increase bone mineral density (BMD) in older persons. OBJECTIVE: A 2-y double-blind study was undertaken to determine whether weekly administration of 10 000 units of vitamin D(2) maintained or increased BMD in younger postmenopausal women more efficiently than did calcium supplements alone. DESIGN: One hundred eighty-seven women who were >or= 1 y postmenopausal were randomly assigned to take either 1000 mg Ca/d after the evening meal or 1000 mg Ca/d plus 10 000 U vitamin D(2)/wk in a double-blind, placebo-controlled format. The BMD of the proximal forearm, lumbar spine, femoral neck, Ward's triangle, and femoral trochanter was measured at 6-mo intervals by osteodensitometry. RESULTS: During the 2-y period, there was no significant difference in the change in BMD at any site between the subjects taking calcium supplements and those taking calcium plus vitamin D(2). Both groups significantly (P < 0.005) gained BMD in Ward's triangle and the femoral trochanter but significantly (P < 0.005) lost bone in the proximal radius. There was no significant change in the lumbar spine or femoral neck BMD. CONCLUSION: In younger postmenopausal women ( age: 56 y) whose average baseline serum 25-hydroxyvitamin D concentration was well within the normal range, the addition of 10 000 U vitamin D(2)/wk to calcium supplementation at 1000 mg/d did not confer benefits on BMD beyond those achieved with calcium supplementation alone.     

Efficacy of commercial and field-strain Mycobacterium paratuberculosis vaccinations with recombinant IL-12 in a bovine experimental infection model

The efficacy of commercial (Strain 18) and field-isolate paratuberculosis vaccine preparations was investigated. The effect of prior exposure to Mycobacterium paratuberculosis and the adjuvant effect of rIL-12 on vaccine efficacy were also tested. Both Strain 18 and field-isolate vaccines induced strong local, systemic and enteric IFN-gamma responses. A significant reduction in mycobacterial colonization was observed when calves were vaccinated with the field-isolate prior to challenge, but not following vaccination with Strain 18 vaccine. Vaccination with rIL-12 prevented infection in some calves but its overall effect on IFN-gamma response and total mycobacterial load was not statistically significant. Efficacy of paratuberculosis vaccines may be enhanced if calves are vaccinated prior to M. paratuberculosis exposure with field-isolate vaccine instead of Strain 18 vaccine currently in use.     

Residents' perceptions of effective community representation in local health decision-making

Community participation in local health decision-making has been envisioned as a key strategy to improve the design and delivery of health services in the USA. While much literature has sought to understand this participatory approach, considerably fewer studies have engaged the essential first-order question: How would we know who the appropriate community representatives are? An important first analytic step is to learn from community members themselves what characteristics they feel a ‘good' representative should possess. Two primary research questions are addressed: 1) To what degree can low-income adults identify and articulate what they believe constitutes an effective community health representative and 2) What do low-income adults believe are the specific characteristics an effective community health representative should possess? In-depth, open-ended interviews were conducted with 14 African-American and Latino residents of four low-income communities on the Southside of Chicago, USA. A theoretical sampling strategy was used with residents varying by age, education, employment, and years of residence on the Southside. We found that respondents had difficulty articulating what a community health representative might do or generating the names of potential representatives, but were able to express clear preferences for what would constitute good representation when given meaningful choices. Three primary characteristics were identified: 1) outcomes 2) expertise, and 3) active communication. These characteristics did not operate in isolation but together communicated the trust and commitment that respondents found fundamental to representation. In exploring this essential yet often neglected question, we sought to build an empirical foundation to more fully examine the precursors to effective community health representation. These data provide important clues as to how to build an inclusive process that expands rather than constrains the pool of community-based representatives.     

Neuroprotection against oxidative injury by a nucleic acid-based health product (Squina DNA) through enhancing mitochondrial antioxidant status and functional capacity

High levels of reactive oxygen species inflict oxidative damage on various cellular components that eventually culminate in a variety of diseases. This study investigated the cytoprotective effects of a nucleic acid-based health product (Squina [Hong Kong, China] DNA) against oxidative stress, particularly in neuronal cells. Adult female Sprague-Dawley rats were treated with Squina DNA, and changes in mitochondrial antioxidant status and functional capacity were assessed by the activities of antioxidant enzymes and ATP generation capacity in brain, heart ventricular, kidney, skeletal muscle, and liver tissues of control and Squina DNA-treated rats. The effects of Squina DNA pretreatment on brain/neuronal cell injury were investigated in a rat model of cerebral ischemia/reperfusion (I/R) injury and a neuroblastoma SH-SY5Y cell model of β-amyloid (Aβ) protein fragment 25-35-induced toxicity. Long-term Squina DNA treatment caused dose-dependent increases in mitochondrial antioxidant status and functional capacity in rat brain, heart ventricular, kidney, skeletal muscle, and liver tissues. Squina DNA pretreatment significantly prevented I/R injury in brain tissue. The cerebroprotection was associated with a reversal of I/R-induced impairment in mitochondrial antioxidant status and disruption in membrane integrity. Squina DNA ethanol extract also significantly inhibited the Aβ-induced apoptosis in SH-SY5Y neuronal cells, as evidenced by less caspase 3 and caspase 9 activation as well as mitochondrial cytochrome c release in Aβ-challenged cells. Squina DNA may enhance the resistance of tissues and cells to oxidative stress, particularly in pathological conditions such as stroke and aging-related neurodegenerative diseases.