Hyperoxia but not ambient pressure decreases tetrahydrobiopterin level without affecting the enzymatic capability of nitric oxide synthase in human endothelial cells

Nitric oxide (NO) seems to be related to bubble formation and endothelial dysfunction resulting in decompression sickness. Bubble formation can be affected by aerobic exercise or manipulating NO. A prior heat stress (HS) has been shown to confer protection against decompression sickness in rats. An important question was if the oxidative environment experienced during diving limits the availability of the nitric oxide synthase (NOS) cofactor tetrahydrobiopterin (BH4). Human endothelial cells were used to investigate how HS and simulated diving affected NO synthesis and defense systems such as heat shock protein 70 (HSP70) and glutathione (GSH). BH4 was measured using a novel LC–MS/MS method and NOS by monitoring the conversion of radiolabeled l-arginine to l-citrulline. Increased pO₂ reduced BH4 levels in cells in a dose-dependent manner independently of high pressure. This effect may result in decreased generation of NO by NOS. The BH4 decrease seemed to be abolished when cells were exposed to HS prior to hyperoxia. NOS enzyme was unaffected by increased pO₂ but substantially reduced after HS. The BH4 level seemed to a minor extent to be dependent upon GSH and probably to a higher degree dependent on other antioxidants such as ascorbic acid. A simulated dive at 60 kPa O₂ had a potentiating effect on the heat-induced HSP70 expression, whereas GSH levels were unaffected by hyperoxic exposure. HS, hyperoxia, and dive affected several biochemical parameters that may play important roles in the mechanisms protecting against the adverse effects of saturation diving.     

Structural evolution of water and hydroxyl groups during thermal,mechanical and chemical treatment of high purity natural quartz

Fused silica crucibles are commonly used in the fabrication process of solar grade silicon ingots. These crucibles are manufactured from high purity natural quartz sand and as a consequence, their properties are influenced by the presence of water and hydroxyls in the raw quartz. In this work, diffuse reflectance IR, ¹H magic angle spinning NMR, and Raman spectroscopy were used to investigate the influence of thermal treatment on water and hydroxyl groups in high purity natural quartz sand. Most of the water in dry sand is present in the form of closed inclusions within the quartz grains which were detected in Raman imaging studies, even after thermally treating the samples at 600 °C. Only after heating to 900 °C did this water completely vanish, most likely as a result of rupturing of the inclusions. However, newly formed OH groups, identified as isolated and hydrogen bound OH were observed as products of the reaction between water and quartz. Similarly, liquid water was observed in NMR spectra even after treatment at 600 °C while at temperatures >900 °C, only non-interacting silanol groups were present. The comparison of the temperature dependence of the IR and NMR spectra also yields insight into the assignment of the OH stretching mode region of the IR spectrum in this system. The intensity of water related bands decreases while the intensity of OH bands first increases and then decreases with increasing temperature. The band intensity of Al-rich defects as well as the characteristic feature at 3200 cm⁻¹ does not follow the temperature dependence of typical water peaks. It is also shown that leaching the quartz sand in HF solution helps to remove water from inclusions, likely by forming pathways for fluid flow inside the quartz grains. Milling of the samples caused formation of an additional type of hydroxyl group, possibly due to partial amorphisation of the surfaces of the quartz grains surface during the process. The results improve the basis for a knowledge-based processes development for the processing of high purity natural quartz.

In dry quartz stable closed liquid micron-size inclusions and newly formed OH groups were observed after thermal treatment.     

Outcomes of a Peritoneal Dialysis Program in Remote Communities Within Colombia

♦ Background and Objective: Colombia is a country of diverse geographic regions, some with mountainous terrain that can make access to urban areas difficult for individuals who live in remote areas. In 2005, a program was initiated to establish remote peritoneal dialysis (PD) centers in Colombia to improve access to PD for patients with end-stage renal disease who face geographic or financial access barriers.♦ Patients and Methods: The present study was a multi-center cohort observational study of prevalent home PD patients who were at least 18 years of age and were being managed by one of nine established remote PD centers in Colombia over a 2-year period. Data were collected from clinical records, databases, and patient interviews. Patient survival, incidence of peritonitis, and rate of withdrawal from PD therapy were assessed.♦ Results: A total of 345 patients were eligible for the study. The majority (87.8%) of patients lived on one to two times a minimum monthly salary (equivalent to US$243 – US$486). On average, patients traveled 1.2 hours and 4.3 hours from their home to their remote PD center or an urban reference renal clinic, respectively. The incidence rate of peritonitis was 2.54 episodes per 100 patient-months of therapy. A bivariate analysis showed a significantly higher risk of peritonitis in patients who were living on less than one times a monthly minimum salary (p < 0.05) or who had a dirt, cement, or unfinished wood floor (p < 0.05). The 1-year and 2-year patient survival rates were 92.44% and 81.55%, respectively. The 1-year and 2-year technique survival rates were 97.27% and 89.78%, respectively.♦ Conclusions: With the support of remote PD centers that mitigate geographic and financial barriers to healthcare, home PD therapy is a safe and appropriate treatment option for patients who live in remote areas in Colombia.     

Same host,same lagoon,different transmission pathways: effects of exogenous factors on larval emergence in two marine digenean parasites

Due to their shallow and confined nature, lagoons provide excellent conditions for the transmission of digenean trematode parasites that require two or more intermediate hosts for the completion of their complex life cycles. However, these unstable environments are characterised by an internal heterogeneity and a large variation of a range of abiotic variables. We conducted a series of experiments in a comparative framework to assess the effect of a number of exogenous factors known to exhibit marked fluctuations in the lagoonal environment, i.e. temperature, salinity, water level and photoperiod, on larval emergence of two sympatric parasites, Cainocreadium labracis and Macvicaria obovata, which share the snail intermediate host, Gibbula adansonii, and a sit-and-wait downstream host-finding strategy. Our results demonstrated contrasting patterns and rates of larval emergence indicating an overall differential response of the two species to the variation of the environmental factors. Cercariae of M. obovata exhibited increased emergence rates at elevated temperature (with a sharp increase at 15 °C), decreased salinity (35–25 practical salinity units (psu)) and low water levels, whereas larval emergence of C. labracis was unaffected by the experimental variation in temperature and water level and showed decreased rates at decreased salinity levels (35–25 psu). The differential impact of the variable environmental conditions indicates the complexity of the patterns of exogenous control modifying parasite transmission and abundance in the lagoonal environment. Most importantly, the contrasting rhythms of larval emergence indicate endogenous control associated with the different transmission pathways of the two opecoelid digeneans.     

Topical rather than intradermal application of the TLR7 ligand imiquimod leads to human dermal dendritic cell maturation and CD8+ T‐cell cross‐priming

Toll‐like receptor (TLR) ligands are attractive candidate adjuvants for therapeutic cancer vaccines, since TLR signaling stimulates and tunes both humoral and cellular immune responses induced by dendritic cells (DCs). Given that human skin contains a dense network of DCs, which are easily accessible via (intra‐)dermal delivery of vaccines, skin is actively explored as an antitumor vaccination site. Here we used a human skin explant model to explore the potential of TLR ligands as adjuvants for DC activation in their complex microenvironment. We show that topical application of Aldara skin cream, 5% of which comprises the TLR7 agonist imiquimod, significantly enhanced DC migration as compared with that resulting from intradermal injection of the TLR7/8 ligand R848 or the soluble form of imiquimod. Moreover, Aldara‐treated DCs showed highest levels of the costimulatory molecules CD86, CD83, CD40, and CD70. Topical Aldara induced the highest production of pro‐inflammatory cytokines in skin biopsies. When combined with intradermal peptide vaccination, Aldara‐stimulated DCs showed enhanced cross‐presentation of the melanoma antigen MART‐1, which resulted in increased priming and activation of MART‐1‐specific CD8⁺ T cells. These results point to advantageous effects of combining the topical application of Aldara with antitumor peptide vaccination.