Multiple Infections, Nutrient Deficiencies, and Inflammation as Determinants of Anemia and Iron Status during Pregnancy: The MINDI Cohort.

In pregnant women with multiple infections, nutrient deficiencies, and inflammation (MINDI), the study of anemia and iron status is limited. For this cross-sectional study (n = 213 Panamanian indigenous women), we investigated if hemoglobin, anemia (Hb < 110 g/L), ferritin, serum iron, serum transferrin receptor, and hepcidin were associated with (1) maternal nutritional status and supplementation practices, (2) biomarkers of inflammation, and (3) presence/absence of infections. Hierarchical generalized linear and logistic regression models and dominance analyses identified the relative importance of these predictors. Anemia (38%), which was likely underestimated due to low plasma volume (95%), was associated with lower ferritin, vitamin A, and weight-for-height, suggesting anemia of undernutrition. Inflammation was not associated with Hb or anemia; nevertheless, higher CRP was associated with increased odds of low serum iron and higher ferritin and hepcidin, indicating iron restriction due to inflammation. The length of iron supplementation did not enter models for anemia or iron indicators, but a multiple nutrient supplement was associated with higher ferritin and hepcidin. Moreover, iron supplementation was associated with higher odds of vaginal trichomoniasis but lower odds of caries and bacterial vaginosis. The complex pathogenesis of anemia and iron deficiency in MINDI settings may require other interventions beyond iron supplementation.

Changes in the Carotenoids of Zamia dressleri Leaves during Development.

It has been observed that the leaves of some Zamia species undergo a kind of "reverse ripening"; that is, they change from their original brown color to green during development. We assumed that this strange color change was due to the change in carotenoid composition, so we followed the changes for several weeks. The detailed carotenoid composition and content at different stages of development of the leaves was determined with HPLC-DAD focusing on the changes in red and yellow carotenoids. The total and relative amounts of red and yellow carotenoids were determined simultaneously from one measurement from a saponified and/or unsaponified extract. At the beginning of development, the concentration of red carotenoids was higher than that of the yellow ones; it decreased drastically until 22 days and continued to decrease slowly until they completely disappeared. The concentration of yellow carotenoids decreased at the beginning as well, but after 22 days it started to increase. The amount of red carotenoids started to decrease when the leaflet stopped growing. Lutein is the main component in old leaflets, which is not a red carotenoid precursor. Red carotenoids can always be found in their esterified form in the leaves. These findings support the hypothesis that red and yellow carotenoid accumulation are independent and probably have different functions in the leaflet. The strange color change was explained based on the compartmentalization of red and yellow carotenoids and on the changing activity of the enzyme capsanthin-capsorubin synthase responsible for the synthesis of red carotenoids capsorubin and capsanthin.

Multiple Indicators of Undernutrition, Infection, and Inflammation in Lactating Women Are Associated with Maternal Iron Status and Infant Anthropometry in Panama: The MINDI Cohort.

Maternal infections, nutrient deficiencies, and inflammation (MINDI) co-exist in lactating indigenous women in Panama, but their impact on maternal iron status and infant growth is unknown. For this secondary analysis of cross-sectional data of lactating mothers from our MINDI cohort, we investigated associations of MINDI variables with maternal anemia, elevated serum transferrin receptor (sTfR), low serum iron, hepcidin, ferritin, and infant weight-for-age (WAZ), length-for-age (LAZ), and head-circumference-for-age (HCAZ) Z-scores in 99 mother-infant dyads. A bootstrapping resampling procedure preselected covariates for inclusion in multivariable regressions models from chronic maternal infections and nutritional status [folate, vitamins A, D, retinol-binding protein (RBP), insulin-growth factor-1 (IGF-1)] and inflammation [C-reactive protein (CRP), cytokines, platelet indices] indicators. Anemia was prevalent (53.5%) but underestimated due to widespread low plasma volume (<2.2 L, 79.9%) and was associated with indicators of malnutrition [lower IGF-1, body mass index (BMI), vitamin D, and intake of green/leafy vegetables], but not inflammation. Higher CRP was associated with lower serum iron, and higher hepcidin and ferritin, whereas maternal platelets were associated with lower HCAZ (ß = −0.22), WAZ (ß = −0.17), and LAZ (ß = −0.17). Higher LAZ was also associated with maternal serum vitamin D (ß = 0.23), whereas maternal iron supplementation lowered LAZ (ß = −0.22). Assessment of iron status in this MINDI cohort is complex and supplementation strategies must consider consequences for both the mother and the infant.

Pouteria sapota (Red Mamey Fruit): Chemistry and Biological Activity of Carotenoids.

BACKGROUND: Red mamey is the fruit of P. sapota, a tree found in Mesoamerica and Asia. This fruit is considered a nutraceutical due to its multiple beneficial health including antiamyloidogenic activity and potential anti-tumorigenic property. Red mamey contain a variety of carotenoids including novel ketocarotenoids such as sapotexanthin and cryptocapsin. A ketocarotenoid is a chemical compound with a carbonyl group present in the ß-ring or in the double bond chain of a carotenoid. In red mamey, the 3'-deoxy-k-end group in sapotexanthin has proven to be an important pro-vitamin A source, which is essential for maintaining a healthy vision and cognitive processes. OBJECTIVE: This work reviews the current knowledge about the chemistry and biological activities of carotenoids in red mamey. METHOD: An exhaustive extraction is the most usual methodology to isolate and thoroughly characterize the carotenoids present in this fruit. High performance liquid chromatography is used to determine the profile of total carotenoids and its purity, while atmospheric pressure chemical ionization was used to determine their molecular weight and nuclear magnetic resonance determined their structure. RESULT: For each 100 g of fresh weight, 0.12 mg of total carotenoid from this fruit can be obtained. Out of the more than 47 reported carotenoids in red mamey, only 34 have a detailed characterization. CONCLUSION: It is important to continue studying the chemical composition and biological activity of this unique tropical fruit with commercial and nutritional value.

Maternal and cord blood parameters are associated with placental and newborn outcomes in indigenous mothers: A case study in the MINDI cohort / Parámetros maternos y de sangre de cordón asociados con medidas placentarias y del recién nacido: Un estudio de casos en madres indígenas de la cohorte MINDI

Abstract Background: Multiple infections, nutrient deficiencies and inflammation (MINDI) occur in indigenous communities, but their associations with perinatal outcomes have not been described. Objective: To assess maternal and cord blood micronutrient and inflammation status in peripartum mothers from the Ngäbe-Buglé comarca in Panama, and their associations with placental and infant outcomes. Methods: In 34 mother-newborn dyads, placental weight and diameter were measured, and maternal and cord blood were processed for complete cell counts, serum C-reactive protein, ferritin, serum transferrin receptor (sTfR), vitamins A and D. Blood volumes were calculated using Nadler's formula. Results: Mothers had low plasma volume (<2.8 L, 96%), vitamin A (52.9%), vitamin D (29.4%), iron (58.8%) and hemoglobin (23.5%), but high hematocrit (>40%, 17.6%) and inflammation (C-reactive protein >8.1 mg/L, 85.3%). Birthweights were normal, but low placental weight (35.3%), low head circumference Z-scores (17.6%), and low cord hemoglobin (5.9%), iron (79.4%), vitamin A (14.7%) and vitamin D (82.3%) were identified. Maternal and cord vitamin D were highly correlated. Higher maternal plasma volume was associated with heavier placentae (β= 0.57), and higher cord D (β= 0.43) and eosinophils (β= 0.43) with larger placentae. Hemoconcentration (higher cord hematocrit) was associated with lower newborn weight (β= -0.48) and head circumference (β= -0.56). Inflammation [higher maternal neutrophils (β= -0.50), and cord platelets (β= -0.32)] was associated with lower newborn length and head circumference. Conclusion: Maternal-newborn hemoconcentration, subclinical inflammation and multiple nutrient deficiencies, particularly neonatal vitamin D deficiency, were identified as potential targets for interventions to improve pregnancy outcomes in vulnerable communities.

Resumen Antecedentes: Las Múltiples Infecciones, Nutrición Deficiente e Inflamación (MINDI), son frecuentes en comunidades indígenas, sin embargo, sus asociaciones con resultados de salud perinatales no han sido descritos. Objetivo: Evaluar la inflamación y los micronutrientes en sangre materna y de cordón de madres en trabajo de parto en la comarca Ngäbe-Buglé en Panamá, así como sus asociaciones con medidas placentarias y del recién nacido. Métodos: En 34 pares madre-recién nacido, se midieron peso y diámetro placentario, y se analizaron muestras de sangre materna y de cordón umbilical para hemograma completo, proteína-C reactiva (PCR), ferritina, receptor sérico de transferrina (RsTf), vitaminas A y D. Se usó la fórmula de Nadler para calcular volúmenes sanguíneos. Resultados: Las madres presentaron volumen plasmático (<2.8 L, 96%), vitamina A (52.9%), vitamina D (29.4%), hierro (58.8%) y hemoglobina (23.5%) bajos, pero el 17.6% presentaron hematocrito >40% y 85.3% presentaron inflamación (PCR >8.1 mg/L). Los pesos al nacer fueron normales, pero se identificó bajo peso placentario (35.3%), bajo puntaje-z de circunferencia cefálica neonatal, y en sangre de cordón, bajos hemoglobina (5.9%), hierro (79.4%), vitamina A (14.7%) y vitamina D (82.3%). Se encontró una fuerte correlación positiva entre la vitamina D materna y de sangre de cordón. Un mayor volumen plasmático materno se asoció con placentas de mayor peso (β= 0.57), en tanto que concentraciones más altas de vitamina D (β= 0.43) y mayor número de eosinófilos (β= 0.43) se asociaron con mayor diámetro placentario. Una mayor hemoconcentración (hematocrito en cordón más alto) se asoció con menores peso al nacer (β= -0.48) y circunferencia cefálica (β= -0.56). La inflamación [mayor número de neutrófilos maternos (β= -0.50) y plaquetas en sangre de cordón (β= -0.32)] se asoció con menor talla y circunferencia cefálica neonatales. Conclusión: La hemoconcentración materna y del recién nacido, la inflamación subclínica y las múltiples deficiencias en micronutrientes, particularmente la deficiencia de vitamina D neonatal, se identificaron como potenciales áreas de intervención para mejorar los resultados de salud del embarazo en comunidades vulnerables.

NLRP3 Regulates IL-4 Expression in TOX+ CD4+ T Cells of Cutaneous T Cell Lymphoma to Potentially Promote Disease Progression.

In cutaneous T cell lymphoma (CTCL), a dominant Th2 profile associated with disease progression has been proposed. Moreover, although the production and regulation of IL-4 expression during the early stages of the disease may have important implications in later stages, these processes are poorly understood. Here, we demonstrate the presence of TOX+ CD4+ T cells that produce IL-4+ in early-stage skin lesions of CTCL patients and reveal a complex mechanism by which the NLRP3 receptor promotes a Th2 response by controlling IL-4 production. Unassembled NLRP3 is able to translocate to the nucleus of malignant CD4+ T cells, where it binds to the human il-4 promoter. Accordingly, IL-4 expression is decreased by knocking down and increased by promoting the nuclear localization of NLRP3. We describe a positive feedback loop in which IL-4 inhibits NLRP3 inflammasome assembly, thereby further increasing its production. IL-4 induced a potentially malignant phenotype measured based on TOX expression and proliferation. This mechanism of IL-4 regulation mediated by NLRP3 is amplified in late-stage CTCL associated with disease progression. These results indicate that NLRP3 might be a key regulator of IL-4 expression in TOX+ CD4+ T cells of CTCL patients and that this mechanism might have important implications in the progression of the disease.

INTERGROWTH-21 Identifies High Prevalence of Low Symphysis-Fundal Height in Indigenous Pregnant Women Experiencing Multiple Infections, Nutrient Deficiencies, and Inflammation: The Maternal Infections, Nutrient Deficiencies, and Inflammation (MINDI) Cohort.

BACKGROUND: In the absence of ultrasound, symphysis-fundal height (SFH) can assess maternal-fetal well-being as it is associated with gestational age, fetal weight, and amniotic fluid volume. However, other modifiers of SFH, including maternal infections, nutrient deficiencies, and inflammation (MINDI), have not been widely explored. OBJECTIVES: Our objectives were 2-fold: 1) to assess prevalence of low SFH in indigenous Panamanian women using both Pan-American Health Organization (PAHO) and INTERGROWTH-21 standards and 2) to explore associations of SFH with maternal health indicators: infections (oral, skin, urogenital, nematode infections), nutrient deficiencies [protein and iron indicators (ferritin, serum iron, serum transferrin receptor, hepcidin), folate, and vitamins A, D, and B-12], and inflammation [leukocytes, C-reactive protein (CRP), cytokines]. METHODS: For this cross-sectional study, low-SFH-for-gestational-age was assessed using PAHO and INTERGROWTH <10th centile in 174 women at ≥16 weeks of gestation. Bootstrapping selected MINDI variables for inclusion in multivariable fractional polynomial (MFP) logistic regressions for low SFH. Associations of MINDI variables with hepcidin were also investigated. RESULTS: Prevalence of low SFH was 8% using PAHO, but using INTERGROWTH, 50.6% had SFH <10th centile, including 37.9% <3rd centile. Both PAHO-SFH <10th centile and INTERGROWTH-SFH <3rd centile were associated with higher hepcidin (OR = 1.12, P = 0.008, and OR = 3.04, P = 0.001, respectively) and with lower TNF-α (OR = 0.73, P = 0.012, and OR = 0.93, P = 0.015, respectively). Wood-smoke exposure increased the odds of PAHO-SFH <10th centile (OR = 1.19, P = 0.009), whereas higher BMI decreased the odds of INTERGROWTH-SFH <3rd centile (OR = 0.87, P = 0.012). Lower pulse pressure (OR = 0.90, P = 0.009) and lower inflammatory responses [lower lymphocytes (OR = 0.21, P = 0.026), IL-17 (OR = 0.89, P = 0.011)] distinguished SFH <3rd centile from SFH ≥3rd to <10th centiles using INTERGROWTH-21 standards. The MFP regression for hepcidin controlling for SFH (adjusted R 2 = 0.40, P = 0.001) revealed associations with indicators of inflammation (CRP, P < 0.0001; IL-17, P = 0.012), acidic urinary pH (P = 0.008), and higher intake of supplements (P = 0.035). CONCLUSIONS: Associations of low SFH with MINDI variables, including hepcidin, highlight its potential for early detection of multicausal in utero growth faltering.

Maternal and cord blood parameters are associated with placental and newborn outcomes in indigenous mothers: A case study in the MINDI cohort.

Background: Multiple infections, nutrient deficiencies and inflammation (MINDI) occur in indigenous communities, but their associations with perinatal outcomes have not been described. Objective: To assess maternal and cord blood micronutrient and inflammation status in peripartum mothers from the Ngäbe-Buglé comarca in Panama, and their associations with placental and infant outcomes. Methods: In 34 mother-newborn dyads, placental weight and diameter were measured, and maternal and cord blood were processed for complete cell counts, serum C-reactive protein, ferritin, serum transferrin receptor (sTfR), vitamins A and D. Blood volumes were calculated using Nadler's formula. Results: Mothers had low plasma volume (<2.8 L, 96%), vitamin A (52.9%), vitamin D (29.4%), iron (58.8%) and hemoglobin (23.5%), but high hematocrit (>40%, 17.6%) and inflammation (C-reactive protein >8.1 mg/L, 85.3%). Birthweights were normal, but low placental weight (35.3%), low head circumference Z-scores (17.6%), and low cord hemoglobin (5.9%), iron (79.4%), vitamin A (14.7%) and vitamin D (82.3%) were identified. Maternal and cord vitamin D were highly correlated. Higher maternal plasma volume was associated with heavier placentae (ß= 0.57), and higher cord D (ß= 0.43) and eosinophils (ß= 0.43) with larger placentae. Hemoconcentration (higher cord hematocrit) was associated with lower newborn weight (ß= -0.48) and head circumference (ß= -0.56). Inflammation [higher maternal neutrophils (ß= -0.50), and cord platelets (ß= -0.32)] was associated with lower newborn length and head circumference. Conclusion: Maternal-newborn hemoconcentration, subclinical inflammation and multiple nutrient deficiencies, particularly neonatal vitamin D deficiency, were identified as potential targets for interventions to improve pregnancy outcomes in vulnerable communities.

Antecedentes: Las Múltiples Infecciones, Nutrición Deficiente e Inflamación (MINDI), son frecuentes en comunidades indígenas, sin embargo, sus asociaciones con resultados de salud perinatales no han sido descritos. Objetivo: Evaluar la inflamación y los micronutrientes en sangre materna y de cordón de madres en trabajo de parto en la comarca Ngäbe-Buglé en Panamá, así como sus asociaciones con medidas placentarias y del recién nacido. Métodos: En 34 pares madre-recién nacido, se midieron peso y diámetro placentario, y se analizaron muestras de sangre materna y de cordón umbilical para hemograma completo, proteína-C reactiva (PCR), ferritina, receptor sérico de transferrina (RsTf), vitaminas A y D. Se usó la fórmula de Nadler para calcular volúmenes sanguíneos. Resultados: Las madres presentaron volumen plasmático (<2.8 L, 96%), vitamina A (52.9%), vitamina D (29.4%), hierro (58.8%) y hemoglobina (23.5%) bajos, pero el 17.6% presentaron hematocrito >40% y 85.3% presentaron inflamación (PCR >8.1 mg/L). Los pesos al nacer fueron normales, pero se identificó bajo peso placentario (35.3%), bajo puntaje-z de circunferencia cefálica neonatal, y en sangre de cordón, bajos hemoglobina (5.9%), hierro (79.4%), vitamina A (14.7%) y vitamina D (82.3%). Se encontró una fuerte correlación positiva entre la vitamina D materna y de sangre de cordón. Un mayor volumen plasmático materno se asoció con placentas de mayor peso (ß= 0.57), en tanto que concentraciones más altas de vitamina D (ß= 0.43) y mayor número de eosinófilos (ß= 0.43) se asociaron con mayor diámetro placentario. Una mayor hemoconcentración (hematocrito en cordón más alto) se asoció con menores peso al nacer (ß= -0.48) y circunferencia cefálica (ß= -0.56). La inflamación [mayor número de neutrófilos maternos (ß= -0.50) y plaquetas en sangre de cordón (ß= -0.32)] se asoció con menor talla y circunferencia cefálica neonatales. Conclusión: La hemoconcentración materna y del recién nacido, la inflamación subclínica y las múltiples deficiencias en micronutrientes, particularmente la deficiencia de vitamina D neonatal, se identificaron como potenciales áreas de intervención para mejorar los resultados de salud del embarazo en comunidades vulnerables.

Induction of Progenitor Exhausted Tissue-Resident Memory CD8+ T Cells Upon Salmonella Typhi Porins Adjuvant Immunization Correlates With Melanoma Control and Anti-PD-1 Immunotherapy Cooperation.

Immunotherapy has improved the clinical response in melanoma patients, although a relevant percentage of patients still cannot be salvaged. The search for the immune populations that provide the best tumor control and that can be coaxed by immunotherapy strategies is a hot topic in cancer research nowadays. Tumor-infiltrating TCF-1+ progenitor exhausted CD8+ T cells seem to grant the best melanoma prognosis and also efficiently respond to anti-PD-1 immunotherapy, giving rise to a TIM-3+ terminally exhausted population with heightened effector activity. We tested Porins from Salmonella Typhi as a pathogen associated molecular pattern adjuvant of natural or model antigen in prophylactic and therapeutic immunization approaches against murine melanoma. Porins induced protection against melanomas, even upon re-challenging of tumor-free mice. Porins efficiently expanded IFN-γ-producing CD8+ T cells and induced central and effector memory in lymph nodes and tissue-resident (Trm) T cells in the skin and tumors. Porins induced TCF-1+ PD-1+ CD8+ Trm T cells in the tumor stroma and the presence of this population correlated with melanoma growth protection in mice. Porins immunization also cooperated with anti-PD-1 immunotherapy to hamper melanoma growth. Importantly, the potentially protective Trm populations induced by Porins in the murine model were also observed in melanoma patients in which their presence also correlated with disease control. Our data support the use of cancer vaccination to sculpt the tumor stroma with efficient and lasting Trm T cells with effector activities, highlighting the use of Porins as an adjuvant. Furthermore, our data place CD8+ Trm T cells with a progenitor exhausted phenotype as an important population for melanoma control, either independently or in cooperation with anti-PD-1 immunotherapy.

Identification of High-Risk Pregnancies in a Remote Setting Using Ambulatory Blood Pressure: The MINDI Cohort.

Background: Ambulatory blood pressure is a potential tool for early detection of complications during pregnancy, but its utility in impoverished settings has not been assessed. This cross-sectional study aimed to determine whether maternal infections, nutrient deficiencies and inflammation (MINDI) were associated with four measures of maternal blood pressure (BP) and to determine their association with symphysis-fundal-height (SFH). Methods: Environmental and dietary factors, intake of iron and a multiple-nutrient supplement (MNS), markers of inflammation, protein, anemia, folate, vitamins B12, A and D status, and urogenital, skin, oral and intestinal nematode infections were measured in indigenous pregnant Panamanian women. Stepwise multiple linear and logistic regression models explored determinants of systolic and diastolic blood pressure (SBP, DBP), hypotension (SBP < 100 and DBP < 60), mean arterial pressure (MAP), elevated MAP (eMAP), and pulse pressure (PP). Associations of BP with intestinal nematodes and with SFH Z scores (≥16 wk) were also explored. Results: Despite absence of high SBP or DBP, 11.2% of women had eMAP. Furthermore, 24.1% had hypotension. Linear regression showed that hookworm infection was associated with higher SBP (P = 0.049), DBP (P = 0.046), and MAP (P = 0.016), whereas Ascaris was associated with lower DBP (P = 0.018) and MAP (P = 0.028). Trichomonas was also associated with lower SBP (P < 0.0001) and MAP (P = 0.009). The presence of Trichuris (OR: 6.7, 95% CI 1.0-44.5) and folic acid deficiency (OR: 6.9, 95% CI 1.4-33.8) were associated with increased odds of eMAP. The odds of low BP was higher in the presence of Ascaris (OR: 3.63 ± 2.28, P = 0.040), but odds were lowered by MNS (OR: 0.35 ± 0.11, P = 0.001), more intake of animal-source foods/wk (OR: 0.7, 95% CI 0.5-0.9) and by higher concentrations of IL-17 (OR: 0.87 ± 0.05, P = 0.016). Conclusion: MINDI were bi-directionally associated with blood pressure indicators. In this MINDI cohort, infections, nutrients and cytokines both raised, and lowered BP indices. The presence of eMAP identified pregnant women at risk of hypertension whereas low PP was associated with lower SFH. Therefore, MAP and PP may help in detecting women at risk of adverse pregnancy outcomes in settings with limited access to technology.

Isolation and identification of sapotexanthin 5,6-epoxide and 5,8-epoxide from red mamey (Pouteria sapota).

Two new carotenoids, sapotexanthin 5,6-epoxide and sapotexanthin 5,8-epoxide, have been isolated from the ripe fruits of red mamey (Pouteria sapota). Sapotexanthin 5,6-epoxide was also prepared by partial synthesis via epoxidation of sapotexanthin, and the (5R,6S) and (5S,6R) stereoisomers were identified by high-performance liquid chromatography-electronic circular dichroism (HPLC-ECD) analysis. Spectroscopic data of the natural and semisynthetic derivatives obtained by acid-catalyzed rearrangement of cryptocapsin 5,8-epoxide stereoisomers were compared for structural elucidation.

Nlrp1b1 negatively modulates obesity-induced inflammation by promoting IL-18 production.

Obesity-induced inflammation, triggered by lipid-mediated activation of the Nlrp3 inflammasome, results in glucose metabolism alterations and type 2 diabetes. This knowledge has been generated using animals deficient for any of the different components of this inflammasome (Caspase-1, Asc or Nlrp3) in the C57BL/6 background. Unlike C57BL/6 mice, which carry allele 2 of the Nlrp1b gene (Nlrp1b2), Balb/c mice that carry allele 1 (Nlrp1b1) are less prone to develop alterations in the glucose metabolism when fed with a high fat diet. However, the molecular bases for these metabolic differences are unknown. Here we show that the Nlrp1b1 allele down regulates the adipose tissue inflammatory response attenuating glucose intolerance and insulin resistance in obese C57BL/mice. Our results indicate that the positive effects of the Nlrp1b1 inflammasome on glucose tolerance and insulin sensitivity involve IL-18-mediated effects on lipolysis, pointing out that differential expression of allelic variants of genes coding for inflammasome components might control susceptibility or resistance to develop diabetes in obese individuals.

C-reactive protein is differentially modulated by co-existing infections, vitamin deficiencies and maternal factors in pregnant and lactating indigenous Panamanian women.

BACKGROUND: The usefulness of C-reactive protein (CRP) as a non-specific marker of inflammation during pregnancy and lactation is unclear in impoverished populations where co-existing infections and vitamin deficiencies are common. METHODS: This cross-sectional study in Panama recruited 120 pregnant and 99 lactating Ngäbe-Buglé women from 14 communities in rural Panama. Obstetric history, indoor wood smoke exposure, fieldwork, BMI, vitamins A, B12, D, and folic acid, and inflammation markers (CRP, neutrophil/lymphocyte ratio (NLR), plateletcrit and cytokines) were measured. Multiple regressions explored both associations of CRP with other inflammatory markers and associations of CRP and elevated CRP based on trimester-specific cut-offs with maternal factors, infections and vitamin deficiencies. RESULTS: CRP was higher in pregnancy (51.4 ± 4.7 nmol/L) than lactation (27.8 ± 3.5 nmol/L) and was elevated above trimester specific cut-offs in 21% of pregnant and 30% of lactating women. Vitamin deficiencies were common (vitamin A 29.6%; vitamin D 68.5%; vitamin B12 68%; folic acid 25.5%) and over 50% of women had two or more concurrent deficiencies as well as multiple infections. Multiple regression models highlighted differences in variables associated with CRP between pregnancy and lactation. In pregnancy, CRP was positively associated with greater indoor wood smoke exposure, caries and hookworm and negatively associated with Ascaris and vaginal Lactobacillus and Bacteroides/Gardnerella scores. Consistent with this, greater wood smoke exposure, caries as well as higher diplococcal infection score increased the odds of trimester-elevated CRP concentrations whereas longer gestational age lowered the likelihood of a trimester-elevated CRP. During lactation, folic acid deficiency was associated with higher CRP whereas parity, number of eosinophils and Mobiluncus score were associated with lower CRP. Also, a higher BMI and Trichomonas vaginalis score increased the likelihood of an elevated CRP whereas higher parity and number of eosinophils were associated with lower likelihood of an elevated CRP. CONCLUSIONS: Infections both raise and lower CRP concentrations in pregnant and lactating mothers. Only folic acid deficiency during lactation was associated with higher CRP concentrations. Caution is required when interpreting CRP concentrations in pregnant and lactating women who have co-existing nutrient deficiencies and multiple infections.

Anti-amyloid aggregation activity of novel carotenoids: implications for Alzheimer's drug discovery.

Alzheimer's disease (AD) is the leading cause of dementia, affecting approximately 33.5 million people worldwide. Aging is the main risk factor associated with AD. Drug discovery based on nutraceutical molecules for prevention and treatment of AD is a growing topic. In this sense, carotenoids are phytochemicals present mainly in fruits and vegetables with reported benefits for human health. In this research, the anti-amyloidogenic activity of three carotenoids, cryptocapsin, cryptocapsin-5,6-epoxide, and zeaxanthin, was assessed. Cryptocapsin showed the highest bioactivity, while cryptocapsin-5,6-epoxide and zeaxanthin exhibited similar activity on anti-aggregation assays. Molecular modeling analysis revealed that the evaluated carotenoids might follow two mechanisms for inhibiting Aß aggregation: by preventing the formation of the fibril and through disruption of the Aß aggregates. Our studies provided evidence that cryptocapsin, cryptocapsin-5,6-epoxide, and zeaxanthin have anti-amyloidogenic potential and could be used for prevention and treatment of AD.

Assessment of Novel Curcumin Derivatives as Potent Inhibitors of Inflammation and Amyloid-ß Aggregation in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting the elderly population worldwide. Brain inflammation plays a key role in the progression of AD. Deposition of senile plaques in the brain stimulates an inflammatory response with the overexpression of pro-inflammatory mediators, such as the neuroinflammatory cytokine. interleukin-6. Curcumin has been revealed to be a potential agent for treating AD following different neuroprotective mechanisms, such as inhibition of aggregation and decrease in brain inflammation. We synthesized new curcumin derivatives with the aim of providing good anti-aggregation capacity but also improved anti-inflammatory activity. Nine curcumin derivatives were synthesized by etherification and esterification of the aromatic region. From these derivatives, compound 8 exhibited an anti-inflammatory effect similar to curcumin, while compounds 3, 4, and 10 were more potent. Moreover, when the anti-aggregation activity is considered, compounds 3, 4, 5, 6, and 10 showed biological activity in vitro. Compound 4 exhibited a strong anti-aggregation effect higher than curcumin. Monofunctionalized curcumin derivatives showed better bioactivity than difunctionalized compounds. Moreover, the presence of bulky groups in the chemical structure of curcumin derivatives decreased bioactivity.

Carotenoid Composition of the Fruit of Red Mamey (Pouteria sapota).

The detailed carotenoid analysis of red mamey (Pouteria sapota) was achieved by HPLC-DAD-MS, chemical tests, and cochromatography with authentic samples. Altogether 47 components were detected and 34 identified from the total extract or after fractionation with column chromatography. The main carotenoids were cryptocapsin, sapotexanthin, and capsanthin 5,6-epoxide. Some further minor components containing the κ-end group with or without a hydroxy group and their 5,6-epoxy precursors were identified. Some comments are made about the biosynthesis of κ-carotenoids in red mamey.

Isolation of ß-Cryptoxanthin-epoxides, Precursors of Cryptocapsin and 3'-Deoxycapsanthin, from Red Mamey (Pouteria sapota).

From an extract of red mamey (Pouteria sapota) ß-cryptoxanthin-5,6-epoxide, ß-cryptoxanthin-5',6'-epoxide, 3'-deoxycapsanthin, and cryptocapsin were isolated and characterized by UV-vis spectroscopy, electronic circular dichroism (ECD), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS). Epoxidation of ß-cryptoxanthin delivered the ß-(5'R,6'S)- and (5'S,6'R)-cryptoxanthin-5',6'-epoxides, which were identified by HPLC-ECD analysis. These carotenoids among others are quite common in the fruits of Central America, and as they are natural provitamins A, they should play an important role in the diet of the mostly vitamin A deficient population of this region.

Interactions among urogenital, intestinal, skin, and oral infections in pregnant and lactating Panamanian Ngäbe women: a neglected public health challenge.

Interrelationships among bacteria, protozoa, helminths, and ectoparasites were explored in a cross-sectional survey of 213 pregnant and 99 lactating indigenous women. Prevalences in pregnancy and lactation, respectively, were: vaginitis (89.2%; 46.8%), vaginal trichomoniasis (75.3%; 91.1%), bacterial vaginosis (BV; 60.6%; 63.3%), hookworm (56.6%; 47.8%), asymptomatic bacteriuria/urinary tract infection (AB/UTI; 56.2%; 36.2%), cervicitis (33.3%; 6.3%), vaginal yeast (24.9%; 11.4%), Ascaris (32.5%; 17.4%), vaginal diplococci (20.4%; 31.6%), caries (19.7%; 18.2%), scabies (17.4%; 8.1%), and Trichuris (12.5%; 8.7%). Multiple regressions revealed positive associations during pregnancy (trichomoniasis and AB/UTI; diplococci and Ascaris) and lactation (yeast and scabies). Negative associations were detected in pregnancy (BV and trichomoniasis; hookworm and diplococci) and lactation (BV and yeast). Vaginal Lactobacillus reduced odds of diplococci in pregnancy and lactation, but increased Ascaris eggs per gram (epg) and odds of trichomoniasis in pregnancy and yeast in lactation. These associations raised a concern that treatment of one condition may increase the risk of another.

Native carotenoids composition of some tropical fruits.

Many tropical fruits can be considered a reservoir of bioactive substances with a special interest due to their possible health-promoting properties. The interest in carotenoids from a nutritional standpoint has recently greatly increased, because of their important health benefits. Here we report the native carotenoids composition in six tropical fruits from Panama, which is considered a region of great biodiversity. The native carotenoid composition was directly investigated by an HPLC-DAD-APCI-MS methodology, for the first time. In Corozo 32 different carotenoids were detected, including a high content of ß-carotene and lycopene. Sastra showed the highest content of zeaxanthin among the fruit investigated. In Sapote 22 different carotenoids were detected, including ß-carotene and 10 different zeaxanthin-di-esters. Frutita showed a very high content of the apo-carotenoid ß-citraurin, and of a number of its esters. In Maracuyà chino 14 carotenoids were detected, including a high amounts of mono-esterified lauric acid with ß-cryptoxanthin and with cryptocapsin. Mamey rojo was characterised by ketocarotenoids with κ rings, both hydroxylated and not hydroxylated.

Cryptocapsinepoxide-type carotenoids from red mamey, Pouteria sapota.

New carotenoids, cryptocapsin-5,6-epoxide, 3'-deoxycapsanthin-5,6-epoxide, and cryptocapsin-5,8-epoxides, have been isolated from the ripe fruits of red mamey (Pouteria sapota). Cryptocapsin-5,6-epoxide was prepared by partial synthesis via epoxidation of cryptocapsin, and the (5R,6S)- and (5S,6R)-stereoisomers were identified by HPLC-ECD analysis. Spectroscopic data of the natural (anti) and semisynthetic (syn) derivatives obtained by acid-catalyzed rearrangement of cryptocapsin-5,8-epoxide stereoisomers were compared for structural elucidation. Chiral HPLC separation of natural and semisynthetic samples of cryptocapsin-5,8-epoxides was performed, and HPLC-ECD analysis allowed configurational assignment of the separated stereoisomers.