Bioenergetics of murine lungs infected with respiratory syncytial virus.

BACKGROUND: Cellular bioenergetics (cellular respiration and accompanying ATP synthesis) is a highly sensitive biomarker of tissue injury and may be altered following infection. The status of cellular mitochondrial O(2) consumption of the lung in pulmonary RSV infection is unknown. METHODS: In this study, lung fragments from RSV-infected BALB/c mice were evaluated for cellular O(2) consumption, ATP content and caspase activity. The disease was induced by intranasal inoculation with the RSV strain A2 and lung specimens were analyzed on days 2-15 after inoculation. A phosphorescence O(2) analyzer that measured dissolved O(2) concentration as a function of time was used to monitor respiration. The caspase-3 substrate analogue N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin (Ac-DEVD-AMC) was used to monitor intracellular caspases. RESULTS: O(2) concentration declined linearly with time when measured in a sealed vial containing lung fragment and glucose as a respiratory substrate, revealing its zero-order kinetics. O(2) consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Cellular respiration increased by 1.6-fold (p<0.010) and ATP content increased by 3-fold in the first week of RSV infection. Both parameters returned to levels found in uninfected lungs in the second week of RSV infection. Intracellular caspase activity in infected lungs was similar to uninfected lungs throughout the course of disease. CONCLUSIONS: Lung tissue bioenergetics is transiently enhanced in RSV infection. This energy burst, triggered by the virus or virus-induced inflammation, is an early biomarker of the disease and may be targeted for therapy.

Toxicokinetics of aflatoxin in pregnant mice.

Our objective was to study the toxicokinetics of aflatoxin (AF) in pregnant mice. Aflatoxin B1 (AFB1) was administered intraperitoneally (IP) to groups of pregnant mice in single doses of 20 mg/kg on gestation day (GD) 13 and orally at the same gestational age. Controls received (IP and oral) a proportionate volume of solvent only. Maternal blood was collected at 15, 30, 45, 60, 90, 120, and 150 minutes posttreatment. Their AFB1 contents were determined. Aflatoxin B1 concentrations following maternal exposure to AFB1 were highly correlated with time after exposure. The serum concentrations were predictable and the highest serum levels were seen immediately at 15 minutes in mice given AFs IP and at 30 minutes in those given it orally. The absorption was 5.0 microg/min and elimination was 3.0 microg/min. The toxicokinetics of AFB1 have been delineated. Aflatoxins are easily and rapidly absorbed both from the gastrointestinal tract (GI) tract and through the peritoneum.

Hypovitaminosis D in adolescent females--an analytical cohort study in the United Arab Emirates.

BACKGROUND: Despite living in a sunny country, hypovitaminosis D is common in women of reproductive age in Al Ain, United Arab Emirates (UAE). AIMS AND OBJECTIVES: To establish the prevalence of hypovitaminosis D in adolescent female Emirati nationals and its risk factors. METHODS: This was an analytical prospective cohort study of 350 female Emirati nationals aged 11-18 years attending public schools in Al Ain. Socio-economic status, diet and amount of sun exposure were evaluated by face-to-face interviews. Serum total 25 (OH) vitamin D (D2 + D3) levels were measured by electrochemiluminescence assay. The prevalence of hypovitaminosis D was calculated and the association with risk factors analysed. RESULTS: Data were complete for 293 girls. Only one girl [prevalence 0.3%, 95% confidence interval (CI) 0.01-1.9] had vitamin D sufficiency (serum vitamin D levels >75 nmol/L). Three girls (1.0%, 95% CI 0.2-2.9) had vitamin D insufficiency (50-75 nmol/L), 58 (19.8%, 95% CI 15.0-25.5) were deficient (27.5-50 nmol/L) and 231 (78.8%, 95% CI 68.9-89.6) had severe deficiency (<27.5 nmol/L). Serum vitamin D levels declined between the ages of 11 and 13 years before progressively rising until the age of 18 years but without regaining the levels they were at the age of 11. There was no statistically significant difference between the vitamin D status groups in age, body mass index, accommodation type, family income, percentage of surface area unexposed to the sun when outdoors, consumption of oily fish or total vitamin D intake. CONCLUSION: The finding of a high prevalence of hypovitaminosis D in adolescent females in UAE is of serious concern for their health and that of their infants during their reproductive lives. Adolescent girls with a similar social and cultural background currently living in less sunny, industrialised countries might also be at risk.

Cellular bioenergetics, caspase activity and glutathione in murine lungs infected with influenza A virus.

Inhibition of cellular respiration, oxidation of glutathione and induction of apoptosis have been reported in epithelial cells infected in vitro with influenza A virus (IAV). Here, the same biomarkers were investigated in vivo by assessing the lungs of BALB/c mice infected with IAV. Cellular respiration declined on day 3 and recovered on day 7 post-infection. For days 3-5, the rate (mean±SD) of respiration (µMO2min(-1)mg(-1)) in uninfected lungs was 0.103±0.021 (n=4) and in infected lungs was 0.076±0.025 (n=4, p=0.026). Relative cellular ATP (infected/uninfected) was 4.7 on day 2 and 1.07 on day 7. Intracellular caspase activity peaked on day 7. Cellular glutathione decreased by ≥10% on days 3-7. Lung pathology was prominent on day 3 and caspase-3 labeling was prominent on day 5. IAV infection was associated with suppression of cellular respiration, diminished glutathione, and induction of apoptosis. These functional biomarkers were associated with structural changes noted in infected mice.

Higher prevalence of vitamin D deficiency in mothers of rachitic than nonrachitic children.

Vitamin D deficiency [serum 25-hydroxyvitamin D <25 nmol/L (<10 ng/mL)] was identified in 92% of rachitic Arab children and 97% of their mothers compared with 22% of nonrachitic children and 52% of their mothers. There was a positive correlation between maternal and child vitamin D levels. We conclude that mothers of rachitic children should be investigated and treated for vitamin D deficiency.

Hypovitaminosis D and vitamin D deficiency in exclusively breast-feeding infants and their mothers in summer: a justification for vitamin D supplementation of breast-feeding infants.

OBJECTIVE: To determine the prevalence of hypovitaminosis D in exclusively breast-feeding infants and their mothers in a community where maternal sunshine exposure is low. STUDY DESIGN: Serum levels of calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D (25-OHD), and intact parathyroid hormone were measured in 90 unsupplemented healthy term breast-feeding Arab/South Asian infants and their mothers in summer. Maternal dietary vitamin D intake was also estimated. RESULTS: The median age of infants was 6 weeks. The median serum 25-OHD concentrations in mothers (8.6 ng/mL) and infants (4.6 ng/mL) were low, and 61% of the mothers and 82% of the 78 infants tested had hypovitaminosis D (serum 25-OHD <10 ng/mL). The infants with hypovitaminosis D had elevated serum alkaline phosphatase and a tendency to higher serum intact parathyroid hormone levels. The average daily maternal vitamin D intake from commercial milk was 88 IU. CONCLUSIONS: Hypovitaminosis D is common in summer in exclusively breast-feeding infants and their mothers. The results provide justification for vitamin D supplementation of breast-feeding infants and mothers in the United Arab Emirates. Low vitamin D intake probably contributed to low maternal vitamin D status.