Can exposure to Gymnodinium catenatum toxic blooms influence the impacts induced by Neodymium in Mytilus galloprovincialis mussels? What doesn't kill can make them stronger?

The presence in marine shellfish of toxins and pollutants like rare earth elements (REEs) poses a major threat to human well-being, coastal ecosystems, and marine life. Among the REEs, neodymium (Nd) stands out as a widely utilized element and is projected to be among the top five critical elements by 2025. Gymnodinum catenatum is a phytoplankton species commonly associated with the contamination of bivalves with paralytic shellfish toxins. This study evaluated the biological effects of Nd on the mussel species Mytilus galloprovincialis when exposed to G. catenatum cells for fourteen days, followed by a recovery period in uncontaminated seawater for another fourteen days. After co-exposure, mussels showed similar toxin accumulation in the Nd and G. catenatum treatment in comparison with the G. catenatum treatment alone. Increased metabolism and enzymatic defenses were observed in organisms exposed to G. catenatum cells, while Nd inhibited enzyme activity and caused cellular damage. Overall, this study revealed that the combined presence of G. catenatum cells and Nd, produced positive synergistic effects on M. galloprovincialis biochemical responses compared to G. catenatum alone, indicating that organisms' performance may be significantly modulated by the presence of multiple co-occurring stressors, such those related to chemical pollution and harmful algal blooms. ENVIRONMENTAL IMPLICATIONS: Neodymium (Nd) is widely used in green technologies like wind turbines, and this element's potential threats to aquatic environments are almost unknown, especially when co-occurring with other environmental factors such as blooms of toxic algae. This study revealed the cellular impacts induced by Nd in the bioindicator species Mytilus galloprovincialis but further demonstrated that the combination of both stressors can generate a positive defense response in mussels. The present findings also demonstrated that the impacts caused by Nd lasted even after a recovery period while a previous exposure to the toxins generated a faster biochemical improvement by the mussels.

How Biological Activity in Sea Cucumbers Changes as a Function of Species and Tissue.

Biological activity and bioactive compound content in sea cucumbers was assessed, considering Parastichopus regalis, Holothuria mammata, Holothuria forskali, and Holothuria arguinensis as species and intestine, muscle band, respiratory tree, body wall, and gonads as tissues. P. regalis had the lowest content in phenolic compounds and antioxidant activity in contrast to Holothuria species. In the respiratory tree, the highest phenolic concentration was recorded in H. arguinensis, 76.4 ± 1.2 mg GAE/100 g dw vs. 21.0-49.0 mg GAE/100 g dw in the other species. H. arguinensis had the highest DPPH and FRAP results in the gonads, 13.6 ± 0.7 mg AAE/100 g dw vs. 2.6-3.5 mg AAE/100 g dw and 27.1 ± 0.3 µmol Fe2+/g dw vs. 8.0-15.9 µmol Fe2+/g dw, respectively. Overall, P. regalis biomass presented the highest anti-inflammatory activity levels and H. arguinensis the lowest anti-inflammatory levels. The respiratory tree was the most anti-inflammatory (measured by the inhibition of cyclooxygenase-2, COX-2) tissue in H. mammata and H. forskali (also the muscle band in this case), 76.3 ± 6.3% and 59.5 ± 3.6% COX-2 inhibition in 1 mg/mL aqueous extracts, respectively. The results demonstrated a variable bioactive potential and advantage in targeting antioxidant properties in the muscle band and anti-inflammatory activity in the respiratory tree, which may constitute a starting point for a biorefinery approach envisaging multiple applications.

Antioxidant and Anti-inflammatory Extracts From Sea Cucumbers and Tunicates Induce a Pro-osteogenic Effect in Zebrafish Larvae.

Bone metabolic disorders such as osteoporosis are characterized by the loss of mineral from the bone tissue leading to its structural weakening and increased susceptibility to fractures. A growing body of evidence suggests that inflammation and oxidative stress play an important role in the pathophysiological processes involved in the rise of these conditions. As the currently available therapeutic strategies are often characterized by toxic effects associated with their long-term use, natural antioxidants and anti-inflammatory compounds such as polyphenols promise to be a valuable alternative for the prevention and treatment of these disorders. In this scope, the marine environment is becoming an important source of bioactive compounds with potential pharmacological applications. Here, we explored the bioactive potential of three species of holothurians (Echinodermata) and four species of tunicates (Chordata) as sources of antioxidant and anti-inflammatory compounds with a particular focus on polyphenolic substances. Hydroethanolic and aqueous extracts were obtained from animals' biomass and screened for their content of polyphenols and their antioxidant and anti-inflammatory properties. Hydroethanolic fractions of three species of tunicates displayed high polyphenolic content associated with strong antioxidant potential and anti-inflammatory activity. Extracts were thereafter tested for their capacity to promote bone formation and mineralization by applying an assay that uses the developing operculum of zebrafish (Danio rerio) to assess the osteogenic activity of compounds. The same three hydroethanolic fractions from tunicates were characterized by a strong in vivo osteogenic activity, which positively correlated with their anti-inflammatory potential as measured by COX-2 inhibition. This study highlights the therapeutic potential of polyphenol-rich hydroethanolic extracts obtained from three species of tunicates as a substrate for the development of novel drugs for the treatment of bone disorders correlated to oxidative stress and inflammatory processes.

Randomized, controlled clinical trial of zinc supplementation to prevent immunological failure in HIV-infected adults.

BACKGROUND: Adequate zinc is critical for immune function; however, zinc deficiency occurs in >50% of human immunodeficiency virus (HIV)-infected adults. We examined the safety and efficacy of long-term zinc supplementation in relation to HIV disease progression. METHODS: A prospective, randomized, controlled clinical trial was conducted involving 231 HIV-infected adults with low plasma zinc levels (<0.75 mg/L), who were randomly assigned to receive zinc (12 mg of elemental zinc for women and 15 mg for men) or placebo for 18 months. The primary end point was immunological failure. HIV viral load and CD4(+) cell count were determined every 6 months. Questionnaires, pill counts, and plasma zinc and C-reactive protein levels were used to monitor adherence to study supplements and antiretroviral therapy. Intent-to-treat analysis used multiple-event analysis, treating CD4(+) cell count <200 cells/mm(3) as a recurrent immunological failure event. Cox proportional hazard models and the general-linear model were used to analyze morbidity and mortality data. RESULTS: Zinc supplementation for 18 months reduced 4-fold the likelihood of immunological failure, controlling for age, sex, food insecurity, baseline CD4(+) cell count, viral load, and antiretroviral therapy (relative rate, 0.24; 95% confidence interval, 0.10-0.56; P<.002). Viral load indicated poor control with antiretroviral therapy but was not affected by zinc supplementation. Zinc supplementation also reduced the rate of diarrhea by more than half (odds ratio, 0.4; 95% confidence interval, 0.183-0.981; P=.019), compared with placebo. There was no significant difference in mortality between the 2 groups. CONCLUSIONS: This study demonstrated that long-term (18-month) zinc supplementation at nutritional levels delayed immunological failure and decreased diarrhea over time. This evidence supports the use of zinc supplementation as an adjunct therapy for HIV-infected adult cohorts with poor viral control. Trial registration. ClinicalTrials.gov identifier: NCT00149552.

Alcohol use accelerates HIV disease progression.

The effects of alcohol abuse on HIV disease progression have not been definitively established. A prospective, 30-month, longitudinal study of 231 HIV(+) adults included history of alcohol and illicit drug use, adherence to antiretroviral therapy (ART), CD4(+) cell count, and HIV viral load every 6 months. Frequent alcohol users (two or more drinks daily) were 2.91 times (95% CI: 1.23-6.85, p = 0.015) more likely to present a decline of CD4 to

Crack-cocaine use accelerates HIV disease progression in a cohort of HIV-positive drug users.

BACKGROUND: HIV infection is prevalent among substance abusers. The effects of specific illicit drugs on HIV disease progression have not been established. We evaluated the relationship between substances of abuse and HIV disease progression in a cohort of HIV-1-positive active drug users. METHODS: A prospective, 30-month, longitudinal study was conducted on 222 HIV-1 seropositive drug users in Miami, FL. History of illicit drug, alcohol, and medication use, CD4+ cell count, and viral load were performed every 6 months. RESULTS: Crack-cocaine users were 2.14 times [95% confidence interval (CI): 1.08 to 4.25, P = 0.029] more likely to present a decline of CD4 to

Quality of life, symptomatology and healthcare utilization in HIV/HCV co-infected drug users in Miami.

HIV/HCV co-infection is becoming one of the main causes of death in HIV+ persons. We determined quality of life, clinical symptoms and health care utilization in HIV mono-infected and HIV/HCV co-infected chronic drug users. After consenting 218 HIV+ drug users, a physical examination and questionnaires on demographics, quality of life, drugs of abuse, and healthcare utilization were completed. Blood was drawn for HCV status, CD4 cell count, HIV viral load, CBC and chemistry. HIV/HCV co-infected participants had significantly higher risk of having poorer perceived outlook and health, presented significantly more frequent depression and physical symptoms, and used significantly more healthcare services than those infected with HIV only, after adjusting for age, gender, ethnicity, CD4 cell count, and viral load. Diminished quality of life in the HIV/HCV co-infected group was explained by increased frequency of depression, physical symptoms, healthcare utilization, and poor access to HCV treatment in this population.

Coronary Heart Disease (CHD) Risk Factors and Metabolic Syndrome in HIV-Positive Drug Users in Miami.

The frequency of coronary heart disease (CHD) is increasing among HIV seropositive persons. This phenomenon may be related to HIV disease itself, the use of antiretroviral medications and increased length of survival, or the synergism of these factors. In this study we have calculated the 10-year CHD risk estimate and the prevalence of metabolic syndrome in a cohort of 118 HIV seropositive chronic drug users, including those who are on HAART with or without protease inhibitors (PI). The results showed that the 10-year coronary heart disease risk among the HIV seropositive drug users was 4.8 ± 5.7, which is within the range of results published for other HIV infected cohorts. The 10-year CHD risk was significantly higher in men (5.9±6.1, p<0.001) than in women (1.7±2.4), due to their gender and the pre-menopausal mean age of the women (39.4±7.3 years of age), despite a significantly higher rate of abdominal obesity (54.8% in women vs. 8.1% in men, p<0.001) and lower HDL (61.3% in women vs. 40% in men, p=0.042). The rate of metabolic syndrome among our female HIV seropositive drug users was significantly higher (29% vs 10.3%, p=0.013) compared to men (10.3%). Participants with metabolic syndrome had a significantly higher 10-year CHD risk (27.8% vs. 10.2%, p=0.041) and higher mean BMI (28.6 ± 4.1 vs. 24.2±4, p<0.001) than those without the syndrome. The predominant proportion of the cohort had a high viral load, suggesting that their use of illicit drugs has an influence on either adherence or effectiveness of antiretroviral medication. Increased viral load was significantly associated with metabolic syndrome (OR=2.23, 95% CI:1.12, 4.47; p=0.023), high fasting glucose (OR=1.61, 95% CI: 1.02, 2.55; p=0.042) and low HDL levels (OR=1.41, 95% CI: 1.01, 1.98; p=0.046), after controlling for age gender, smoking, PI exposure, BMI and CD4. HAART with or without PI did not significantly impact the 10-year CHD risk estimate or metabolic syndrome in this cohort. The estimated effect of PI, however, was positively and significantly related to triglyceride levels (effect estimate=95.81; 95% CI:39.40, 152.21; p<0.01) after controlling for age, gender, smoking, viral load, CD4 cell count and BMI. Heavy use of cigarettes and crack/cocaine was inversely associated with obesity (OR=0.84, 95% CI:0.67, 0.99; p=0.049; OR=0.43, 95% CI:0.19, 0.98; p=0.044, respectively), while use of marijuana tended to be associated with increased central obesity (p=0.08). Heavy cigarette smoking was significantly associated with low HDL (OR=3.06, 95% CI:1.18; 7.95, p=0.02). The significant association of higher viral load with CHD risk indicates that controlling viral load may be important in reducing CHD risk in HIV infected drug users.

HIV-related wasting in HIV-infected drug users in the era of highly active antiretroviral therapy.

BACKGROUND: A decrease in the rate of human immunodeficiency virus (HIV) infection-related wasting has been reported in the era of highly active antiretroviral therapy (HAART). We investigated this concern in a hard-to-reach population of HIV-infected drug users in Miami, Florida. METHODS: After informed consent was obtained, 119 HIV-infected drug users were administered questionnaires involving demographic, medical history, and food-security information. Blood samples were drawn for immunological and viral studies. HIV-related wasting over a period of > or =6 months was defined as a body mass index of <18.5 kg/m2, unintentional weight loss of > or =10% over 6 months, or a weight of <90% of the ideal body weight. RESULTS: The prevalence of HIV-related wasting was 17.6%. A significantly higher proportion of those who experienced wasting (81%) reported that there were periods during the previous month when they went for > or =1 day without eating (i.e., food insecurity), compared with those who did not experience wasting (57%). Although a greater percentage of patients who experienced wasting were receiving HAART, their HIV RNA levels were more than twice as high (mean+/-standard deviation [SD], 166,689+/-238,002 copies/mL; median log HIV RNA level +/- SD, 10.2+/-2.7 log10 copies/mL) as those for the group that did not experience wasting (mean+/-SD, 72,156 +/- 149,080; median log HIV RNA level+/-SD, 9.2+/-2.3 log10 copies/mL). Participants who experienced wasting were more likely to be heavy alcohol drinkers and users of cocaine. In multivariate analysis that included age, sex, food security, alcohol use, cocaine use, viral load, and receipt of antiretroviral therapy, the only significant predictors of wasting were > or =1 day without eating during the previous month (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.18-3.26; P=.01) and viral load (OR, 1.64; 95% CI, 1.00-2.69; P=.05). CONCLUSIONS: HIV-related wasting continues to be common among HIV-infected drug users, even among HAART recipients. Food insecurity and viral load were the only independent predictors of wasting. The social and economic conditions affecting the lifestyle of HIV-infected drug users constitute a challenge for prevention and treatment of wasting.