Pulmonary cells exposed to diesel exhaust (DE) particles in vitro respond in a hierarchical fashion with protective antioxidant responses predominating at low doses and inflammation and injury only occurring at higher concentrations. In the present study, the authors examined whether similar responses occurred in vivo, specifically whether antioxidants were upregulated following a low-dose DE challenge and investigated how these responses related to the development of airway inflammation at different levels of the respiratory tract where particle dose varies markedly.A total of 15 volunteers were exposed to DE (100 mg?m -3 airborne particulate matter with a diameter of ,10 mm for 2 h) and air in a double-blinded, randomised fashion. At 18 h postexposure, bronchoscopy was performed with lavage and mucosal biopsies taken to assess airway redox and inflammatory status. Following DE exposure, the current authors observed an increase in bronchial mucosa neutrophil and mast cell numbers, as well as increased neutrophil numbers, interleukin-8 and myeloperoxidase concentrations in bronchial lavage. No inflammatory responses were seen in the alveolar compartment, but both reduced glutathione and urate concentrations were increased following diesel exposure.In conclusion, the lung inflammatory response to diesel exhaust is compartmentalised, related to differing antioxidant responses in the conducting airway and alveolar regions.
Background: Atlanta has been identified as an HIV “hot spot” for Black women and ranks 5th in the US with new infections. Yet little is known about PrEP eligibility or interest among young Black women in Atlanta. Methods: A convenience sample of 1,261 Black women (ages 14–24 years) were recruited from two settings: community venues and sexual health clinics. They provided self-reported sexual behavior data and specimens for laboratory testing for chlamydia (CT) and gonorrhea (GC) infections. For each woman, the number of key self-reported behavioral HIV risk factors was calculated (0–6 factors for the clinic sample, 0–3 factors for the community sample). A single item assessed PrEP interest in the community sample only. Results: Bacterial STI positivity, an indicator for PrEP eligibility, was 20.5% (17.1% CT, 6.3% GC) and 20.9% (18.8% CT, 5.2% GC) for the clinic and community samples, respectively. Of the 144 STI positive women from the clinic sample, 20.1% reported no behavioral risk indicators and 47.2% reported ≥ 2 behavioral indicators. Of the 117 STI positive women from the community sample, 21.4% reported no behavioral risk indicators. 60.7% of the community sample reported they would be likely or very likely to use PrEP if available. Conclusion: Young Black women in Atlanta, whether sampled from community or sexual health settings, are at substantial risk for HIV infection and meet several PrEP eligibility criteria. Scaling up PrEP among women in Atlanta could have significant implications for HIV in this high burden region.
Marked hyperleptinaemia and metabolic acidosis are common findings in patients with chronic renal failure. In animal models, both leptin administration and acidosis reduce food intake. However, leptin causes loss of body fat, while acidosis induces muscle wasting. Whether a low pH and leptin production are related has not been studied. Leptin secretion was measured in cultured 3T3-L1 adipocytes exposed to acid or control pH for up to 96 h. In addition, serum leptin was compared between acidotic and bicarbonate-treated uraemic Wistar rats using the remnant model. Leptin levels in the culture medium were decreased at an acid pH of 7.1 compared with a control pH of 7.5 at 96 h (562+/-78 and 831+/-103 pg.48 h(-1). well(-1) respectively; mean+/-S.E.M.; P=0.037). Similarly, serum leptin in uraemic rats was found to be lower in the acidotic group than in the bicarbonate-treated group, although this observation fell just short of statistical significance (1273+/-171 compared with 2059+/-376 pg/ml; P=0.07). In conclusion, acidosis decreases leptin secretion from cultured adipocytes. Accordingly, acidotic uraemic rats seem to exhibit lower serum leptin levels than their bicarbonate-supplemented counterparts. This study is the first report providing a link between acidosis and leptin levels.
Part. I: Prostaglandin F2Α (PGF2Α) was shown to be ‘the’ luteolysin in the ewe on the following criteria: (1) Hysterectomy and/or separation of the uterine horn from the ovary bearing a corpus luteum led to prolongation of the oestrous cycle, (2) PGF2Α shortened the cycle when administered in the midluteal phase, (3) PGF2Α was identified in uterine venous blood, (4) a mechanism for the transfer of PGF2Α from the uterine vein to the ovarian artery was shown to exist, (5) the quantitative aspects of the secretion transfer mechanism and luteolytic potency of PGF2Α were adequate to account for the observed phenomena. Part II: These criteria were applied for evaluation of PGF2Α as ‘the’ luteolysin in the following species: cattle, goat, horse, pig, guinea pig, rat, hamster, rabbit, monkey, human. On present knowledge, there appeared to be a variation between species from those in which PGF2Α was probably concerned in luteolysis and those in which the evidence was against such a role. Part III: PGF2Α was shown to be luteolytic when given by continuous infusion for 3–6 h into the lumen of the uterus in cattle as well as sheep. The minimum effective dose was of the order of 7 g/kg. The application of this finding to artificial insemination programmes was discussed.
Mice of strain DBA/2J were found to produce red cells considerably more resistant to osmotic lysis than cells from C57BL/6J or the F1 hybrid between the two strains. Such strain-specific differences in osmotic fragility could be the result of genetically determined humoral or other systemic differences that indirectly influence red cell properties. Alternatively, this phenotypic variation might be an inherent property of the erythrocyte themselves and be directly controlled by their genotype. Analysis of red cells from allophenic (mosaic) mice of the strain composition C57BL/6J in equilibrium DBA/2J demonstrated that the latter possibility is the case. In such mice, erythrocytes of the DBA/2J genotype are relatively more resistant to osmotic lysis than are those of the C57BL/6J genotype; partial lysis of allophenic blood at intermediate salt concentrations results in marked enrichment for DBA/2J cells among the survivors. Future experiments designed to determine the mechanism underlying this difference can now focus on the properties of the red blood cells per se with the certainty that this property is inherent to the genotype of each cell.
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