Behaviors associated with sickness (food consumption, weight maintenance, exploratory activity and grooming frequency) were examined on post-surgical days 1, 3, 5, 7 and 9 in male rats treated with progesterone (4. mg/kg) and/or vehicle. Rats with medial frontal cortex contusions showed reduced food consumption on days 1 and 3 (p< 0.01), reduced weight maintenance on days 1, 3, 5, 7 and 9 (p< 0.01), reduced grooming frequency on day 1 (p< .01), and reduced exploratory activity on day 1 (p< 0.01), after injury compared to sham rats. Contusion induced behaviors were not attenuated with 5 days of progesterone treatment (p> 0.05). Progesterone did reduce lesion size at 9 days after injury (p< 0.05). Our results suggest sickness behaviors occur after traumatic brain injury and that they might not respond to some neurosteroidal agents.
Fructose-sweetened liquid consumption is associated with fatty liver and oxidative stress. In rodent models of fructose-mediated fatty liver, protein consumption is decreased. Additionally, decreased sulfur amino acid intake is known to cause oxidative stress. Studies were designed to test whether oxidative stress in fructose-sweetened liquid-induced fatty liver is caused by decreased ad libitum solid food intake with associated inadequate sulfur amino acid intake. C57BL6 mice were grouped as: control (ad libitum water), fructose (ad libitum 30% fructose-sweetened liquid), glucose (ad libitum 30% glucose-sweetened water) and pair-fed (ad libitum water and sulfur amino acid intake same as the fructose group). Hepatic and plasma thiol-disulfide antioxidant status were analyzed after five weeks. Fructose- and glucose-fed mice developed fatty liver. The mitochondrial antioxidant protein, thioredoxin-2, displayed decreased abundance in the liver of fructose and glucose-fed mice compared to controls. Glutathione/glutathione disulfide redox potential (E hGSSG) and abundance of the cytoplasmic antioxidant protein, peroxiredoxin-2, were similar among groups. We conclude that both fructose and glucose-sweetened liquid consumption results in fatty liver and upregulated thioredoxin-2 expression, consistent with mitochondrial oxidative stress; however, inadequate sulfur amino acid intake was not the cause of this oxidative stress.
Background: We hypothesized that maternal alcohol use occurs in pregnancies that end prematurely and that in utero alcohol exposure is associated with an increased risk of morbidities of premature newborns.
Methods: In an observational study of mothers who delivered very low birth weight newborns (VLBW) ≤1,500 g, maternal alcohol use was determined via a standardized administered questionnaire. We compared the effect of maternal drinking on the odds of developing late-onset sepsis (LOS), bronchopulmonary dysplasia (BPD), death, BPD or Death days on oxygen or any morbidity (either LOS, BPD or death). The effect of drinking amounts (light versus heavy) was also evaluated.
Results: A total of 129 subjects who delivered 143 VLBW newborns were enrolled. Approximately 1 in 3 (34%) subjects reported drinking alcohol during the first trimester ("exposed"). Within the exposed group, 15% reported drinking ≥7. drinks/week ("heavy") and 85% of the subjects reported drinking < 7. drinks/week ("light"). When controlling for maternal age, drug or tobacco use during pregnancy and neonatal gestational age, any drinking increased the odds of BPD or Death and any morbidity. Furthermore, light or heavy drinking increased the odds of BPD or Death and any morbidity, whereas heavy drinking increased the odds of LOS.
Conclusions: In utero alcohol exposure during the first trimester occurred in 34% of VLBW newborns. Maternal drinking in the first trimester was associated with significantly increased odds of neonatal morbidity. Further studies are warranted to determine the full effect of . in utero alcohol exposure on the adverse outcomes of VLBW premature newborns.
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Phuong H. Nguyen;
Hieu Nguyen;
Ines Gonzalez-Casanova;
Erika Copeland;
Garrett Strizich;
Alyssa Lowe;
Hoa Pham;
Truong V. Truong;
Son Nguyen;
Reynaldo Martorell;
Usha Ramakrishnan
Background: Micronutrient deficiencies are a public health concern worldwide negatively affecting maternal and child health outcomes. The primary underlying causes of micronutrient deficiencies are insufficient intake and poor bioavailability of micronutrients. However, reliable data on micronutrient intakes are sparse. The objectives of this study were to identify the key local food sources providing the majority of micronutrients and assess the adequacy and determinants of micronutrient intakes. Methods: The study used data from a survey of 4,983 rural women of reproductive age (WRA) participating in a preconception micronutrient supplementation trial in Vietnam. Micronutrient intakes were assessed using a validated 107-item semi-quantitative food-frequency questionnaire. Multivariate linear and logist ic regression analyses were used to examine the association between socioeconomic status and micronutrient intakes. Results: Starchy staples were the main source of iron and zinc (37% and 54%, respectively) with only a small proportion from meat (10% and 18%, respectively). The primary source of folate and vitamin A were vegetables; vitamin B12 came from meat and eggs. The proportion of the population with intakes below the estimated average requirement was 25% for iron, 16% for zinc, 54% for folate, 64% for vitamin B12 and 27% for vitamin A. Socioeconomic status was the main determinant of micronutrient intakes. WRA in the highest quintile consumed 26% more iron, 19% more zinc, 36% more folate, 82% more vitamin B12 and 47% more vitamin A compared to those in the lowest quintile. Women in the upper quintiles of SES were more likely to obtain nutrients from more nutritious and higher bioavailable foods than those in the lowest quintile. Conclusions: Underprivileged women were at increased risk for insufficient micronutrient intakes due to poor diet quality. Targeted efforts to promote the consumption of local nutrient rich foods along with educational programs and social development are needed.
Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in humans and accounts for 80-85% of malignant renal tumors. Eker rat represents a unique animal model to study RCC since these rats develop spontaneous renal tumors and leiomyoma, which may be due to tuberous sclerosis 2 (TSC2) mutation resulting in the activation of the mammalian target of rapamycin (mTOR) pathway. This study examines the role of a lycopene-rich diet in the development of RCC in the TSC2 mutant Eker rat model. Ten-week old female Eker rats (n = 90) were assigned in equal numbers to receive 0, 100 or 200 mg/kg of lycopene as part of their daily diet. After 18 months the rats were sacrificed and the kidneys were removed. Immunohistochemical staining with antibodies against mTOR, phospho-S6 and EGFR were performed, as well as hematoxylin-eosin staining for histologic examination of the tumors. Tumors were counted and measured in individual kidneys. Presence of tumor decreased from 94% in control animals to 65% in the experimental group, but the difference was not statistically significant (P < 0.12). However, mean numbers of renal carcinomas were statistically significantly decreased in the lycopene-treated rats (P < 0.008) when compared to untreated controls. In the lycopene group, tumor numbers decreased (P < 0.002) and the numbers tended to decrease linearly (P < 0.003) as supplemental lycopene increased from 0 to 200. Control rats fed only basal diet had a greater length of tumors (23.98 mm) than rats fed lycopene supplement groups (12.90 mm and 11.07 mm) (P < 0.05). Moreover tumor length decreased (P < 0.02) and tumor length tended to decrease linearly (P < 0.03) as supplemental lycopene increased from 0 to 200 mg/kg. All tumors showed strong staining with antibodies against mTOR, phospho-S6 and EGFR. In conclusion, dietary supplementation with lycopene attenuates the development of renal cell cancers in the predisposed TSC2 mutant Eker rat model. These results suggest that lycopene may play a role in the prevention of RCC.
Background:The health implications of in utero alcohol exposure have been difficult to study in very-low-birth-weight newborns (VLBW) because of an inability to identify maternal alcohol exposure. Fatty acid ethyl esters (FAEEs) are elevated in meconium of alcohol-exposed term newborns. We hypothesized that meconium FAEEs would be similarly elevated in alcohol-exposed VLBW premature newborns.
Methods:In a retrospective cohort study of 64 VLBW neonates, newborns were classified into Non-Exposed, Any Exposure, or Weekly Exposure groups based on an in-depth structured maternal interview. Meconium FAEE concentrations were quantified via gas chromatography mass spectrometry.
Results:Alcohol exposure during Trimester 1 (Any Exposure) occurred in ∼30% of the pregnancies, while 11% of the subjects reported drinking ≥ 1 drink/week (Weekly Exposure). Meconium ethyl linolenate was higher in Any Exposure (P = 0.01) and Weekly Exposure groups (P = 0.005) compared to the Non-Exposed VLBW group. There was a significant positive correlation between Trimester 1 drinking amounts and the concentration of meconium ethyl linolenate (P = 0.005). Adjusted receiver operating characteristic (ROC) curves evaluating ethyl linolenate to identify alcohol-exposed VLBW newborns generated areas under the curve of 88% with sensitivities of 86-89% and specificities of 83-88%.
Conclusion:Despite prematurity, meconium FAEEs hold promise to identify the alcohol-exposed VLBW newborn.
Among the many organ systems affected by harmful alcohol use, the lungs are particularly susceptible to infections and injury. The mechanisms responsible for rendering people with alcohol use disorder (AUD) vulnerable to lung damage include alterations in host defenses of the upper and lower airways, disruption of alveolar epithelial barrier integrity, and alveolar macrophage immune dysfunction. Collectively, these derangements encompass what has been termed the "alcoholic lung" phenotype. Alcohol-related reductions in antioxidant levels also may contribute to lung disease in people with underlying AUD. In addition, researchers have identified several regulatory molecules that may play crucial roles in the alcohol-induced disease processes. Although there currently are no approved therapies to combat the detrimental effects of chronic alcohol consumption on the respiratory system, these molecules may be potential therapeutic targets to guide future investigation.
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Lindsay M. Margoles;
Rohit Mittal;
Nathan J. Klingensmith;
John D. Lyons;
Zhe Liang;
Mara A. Serbanescu;
Maylene E. Wagener;
Craig Coopersmith;
Mandy Ford
Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-ã, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.
Background:
Diabetes is an important contributor to global morbidity and mortality. The contributions of population aging and macroeconomic changes to the growth in diabetes prevalence over the past 20 years are unclear.
Methods: We used cross-sectional data on age- and sex-specific counts of people with diabetes by country, national population estimates, and country-specific macroeconomic variables for the years 1990, 2000, and 2008. Decomposition analysis was performed to quantify the contribution of population aging to the change in global diabetes prevalence between 1990 and 2008. Next, age-standardization was used to estimate the contribution of age composition to differences in diabetes prevalence between high-income (HIC) and low-to-middle-income countries (LMICs). Finally, we used non-parametric correlation and multivariate first-difference regression estimates to examine the relationship between macroeconomic changes and the change in diabetes prevalence between 1990 and 2008.
Results: Globally, diabetes prevalence grew by two percentage points between 1990 (7.4 %) and 2008 (9.4 %). Population aging was responsible for 19 % of the growth, with 81 % attributable to increases in the age-specific prevalences. In both LMICs and HICs, about half the growth in age-specific prevalences was from increasing levels of diabetes between ages 45-65 (51 % in HICs and 46 % in LMICs). After age-standardization, the difference in the prevalence of diabetes between LMICs and HICs was larger (1.9 % point difference in 1990; 1.5 % point difference in 2008). We found no evidence that macroeconomic changes were associated with the growth in diabetes prevalence.
Conclusions: Population aging explains a minority of the recent growth in global diabetes prevalence. The increase in global diabetes between 1990 and 2008 was primarily due to an increase in the prevalence of diabetes at ages 45-65. We do not find evidence that basic indicators of economic growth, development, globalization, or urbanization were related to rising levels of diabetes between 1990 and 2008.
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Matthew S. Freiberg;
Ionut Bebu;
Russell Tracy;
Kaku So-Armah;
Jason Okulicz;
Anuradha Ganesan;
Adam Armstrong;
Thomas O'Bryan;
David Rimland;
Amy C. Justice;
Brian K. Agan;
Infectious Disease Clinical Research Program HIV Working Group
The mechanism underlying the excess risk of non-AIDS diseases among HIV infected people is unclear. HIV associated inflammation/hypercoagulability likely plays a role. While antiretroviral therapy (ART) may return this process to pre-HIV levels, this has not been directly demonstrated. We analyzed data/specimens on 249 HIV+ participants from the US Military HIV Natural History Study, a prospective, multicenter observational cohort of >5600 active duty military personnel and beneficiaries living with HIV. We used stored blood specimens to measure D-dimerand Interleukin-6 (IL-6) at three time points: pre-HIV seroconversion, ≥6 months post-HIV seroconversion but prior to ART initiation, and ≥6 months post-ART with documented HIV viral suppression on two successive evaluations. We evaluated the changes in biomarker levels between time points, and the association between these biomarker changes and future non-AIDS events. During a median follow-up of 3.7 years, there were 28 incident non-AIDS diseases. At ART initiation, the median CD4 count was 361 cells/mm3; median duration of documented HIV infection 392 days; median time on ART was 354 days. Adjusted mean percent increase in D-dimer levels from pre-seroconversion to post-ART was 75.1% (95% confidence interval 24.6-148.0, p = 0.002). This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03). Changes in IL-6 levels across time points were small and not associated with future non-AIDS events. In conclusion, ART initiation and HIV viral suppression does not eliminate HIV associated elevation in D-dimer levels. This residual pathology is associated with an increased risk of future non-AIDS diseases.