The potential of folate derivatives and Hantzsch esters to inhibit ultraviolet-induced reactive oxygen species.

Context: Ultraviolet (UV) radiation causes 60,000 premature deaths worldwide per year. In the US alone, UV-associated skin cancers cost over $8 billion annually. UV radiation causes harm primarily through inducing carcinogenic reactive oxygen species (ROS). Agents that reduce UV-induced ROS before carcinogenesis can occur are therefore highly desirable. Folate derivatives and Hantzsch esters have been shown to inhibit chemically-induced ROS, but have not been demonstrated to be effective at inhibiting UV-induced ROS. Objectives: (1) To evaluate in vitro inhibition of UV-induced ROS with a folate derivative. (2) To identify promising Hantzsch esters for further study by evaluating their energy favorability to inhibit some ROS through high precision quantum chemical methods (CBS-QB3, SMD solvent model, water). Study Design and Analysis: UACC 903 cells (Melanoma cell line) and fibroblast cells were cultured and marked with a fluorescent ROS dye. Cells were exposed to varying concentrations of a folate derivative, and ROS were induced by H2O2 or ultraviolet radiation. ROS inhibition was measured over time, and modeled on an S-shaped curve. High precision chemical methods (CBS-QB3, SMD solvent model, water) of elementary reaction steps involving the transfer of electrons (SET step), the transfer of hydrogen radicals and the transfer of hydride anions were used to evaluate the energy favorability of Hantzsch esters as ROS inhibitors and identify promising Hantzsch esters for future in vitro evaluation. Setting: In vitro analysis and quantum calculation. Intervention: Exposure to UV radiation. Outcome Measures: (1) ROS inhibition (2) Net energy of Hantzsch ester ROS interaction. Results: Folate derivatives inhibit ultraviolet radiation-induced ROS in melanoma and fibroblast cell lines in vitro. Several Hantzsch esters demonstrate energy favorability in inhibiting ROS in silico. Conclusions: Folate derivatives and their chemical analogs, Hantzsch esters, offer a method of inhibiting ROS induced by ultraviolet radiation, and hence, a potential method for reducing the tremendous health burden of ultraviolet radiation. Further study is needed to determine the extent to which this ROS inhibition decreased carcinogenesis.

Hyperbaric tracheobronchial compression in cetaceans and pinnipeds.

Assessment of the compressibility of marine mammal airways at depth is crucial to understanding vital physiological processes such as gas exchange during diving. Very few studies have directly assessed changes in cetacean and pinniped tracheobronchial shape, and none have quantified changes in volume with increasing pressure. A harbor seal, gray seal, harp seal, harbor porpoise and common dolphin were imaged promptly post mortem via computed tomography in a radiolucent hyperbaric chamber. Volume reconstructions were performed of segments of the trachea and bronchi of the pinnipeds and bronchi of the cetaceans for each pressure treatment. All specimens examined demonstrated significant decreases in airway volume with increasing pressure, with those of the harbor seal and common dolphin nearing complete collapse at the highest pressures. The common dolphin bronchi demonstrated distinctly different compression dynamics between 50% and 100% lung inflation treatments, indicating the importance of air in maintaining patent airways, and collapse occurred caudally to cranially in the 50% treatment. Dynamics of the harbor seal and gray seal airways indicated that the trachea was less compliant than the bronchi. These findings indicate potential species-specific variability in airway compliance, and cessation of gas exchange may occur at greater depths than those predicted in models assuming rigid airways. This may potentially increase the likelihood of decompression sickness in these animals during diving.

Melon and rostral muscle morphology of Gervais' beaked whale (Mesoplodon europaeus): Alternating patterns of bilateral asymmetry.

Toothed whales utilize specialized nasal structures such as the lipid-rich melon to produce sound and propagate it into the aquatic environment. Very little nasal morphology of mesoplodont beaked whales has been described in the literature, and the anatomy of the melon and associated musculature of Gervais' beaked whale (Mesoplodon europaeus) remains undescribed. Heads of three (n = 3) Gervais' beaked whales were examined in detail via dissection as well as computed tomography (CT) and magnetic resonance imaging (MRI). Two additional Gervais' beaked whale individuals (n = 2) were studied via archived CT and MRI scans. Representative transverse dissection sections of the melon were processed for polarized light imaging to verify the presence of tendons inserting into the melon tissue. Three-dimensional (3D) CT reconstructions of the melon, rostral muscles, and associated structures were performed to assess morphology and spatial relationships. In all individuals, the melon's main body demonstrated a bilaterally asymmetrical, curvilinear geometry. This curvilinear shape was defined by a pattern of alternating asymmetry in the medial rostral muscles that projected into the melon's tissue. In transverse polarized light imaging, a network of tendons originating from these asymmetrical rostral muscle projections was observed permeating the melon's lipid tissue. This curvilinear melon morphology and associated asymmetrical musculature suggest a means of lengthening the lipid pathway within a relatively short dimensional footprint. In addition, the species-specific arrangement of muscular projections suggests complex fine-tuning of the melon's geometry during echolocation. Further studies may lend additional insight into the function of this unusual melon morphology.

Exploring relationship of soil PTE geochemical and "VIS-NIR spectroscopy" patterns near Cu-Mo mine (Armenia).

PTE contamination of soils remains one of the global environmental concerns. The ways of detecting and monitoring PTE concentrations in soils varies including traditional field sampling accompanied by sample preparation and chemical analysis and state of the art visible and near-infrared (Vis-NIR) spectroscopic approaches. Among the different Machine Learning (ML) to extract soil information from spectra and to explore the relationship between spectral reflectance data and soil PTE content PLSR method is a well-established one to construct a soil PTE estimation model. This study aimed to explore the relationship of soil PTE geochemical and VIS-NIR spectroscopy characteristics in agricultural soils near Cu-Mo mine area in Armenia. PLSR method is applied to identify the links between the spectra and agricultural soil Ti, V, Cr, Mn, Fe, Co, Ba, Pb, Zn, Cu, Sr, Zr and Mo contents to reveal the potential of VIS-NIR spectroscopy in ex-situ monitoring of Kajaran soils. The results show that different portions of VIS-NIR spectra are responsible for Ti (1100-1200 nm, 2350-2500 nm), V (350-500 nm, 700-750 nm, 1000-1100 nm, 1400-2500 nm), Cr (1300-1400 nm, 1900-2100 nm) and Ba (450-500 nm, 600-800 nm, 1050-1700 nm, 2000-2100 nm, 2350-2400 nm) estimations through PLSR correspondingly. However, among the studied PTEs Ti and V, which shows significant negative correlations in VIS-NIR spectra registered at around 400-600 nm and 850-1150 nm regions, are remarkable and promising with the PLSR estimation results using VIS-NIR spectra Ti (R2Test = 0.74), V (R2Test = 0.71). This study shows that VIS-NIR spectroscopy has a high potential for the estimation of at least several PTE in soils and PLSR modelis reliable for deriving information from there.

Reduction of halocarbons to hydrocarbons by NADH models and NADH.

The reduction of halocarbons by NADH models and NADH under ambient conditions is reported as a new type of reactivity pointing towards a hitherto unknown disruptive pathway for NADH/NADPH-dependent processes. The reaction was studied with the omnipresent pesticide DDT, the inhalation anesthetic halothane, and several simple halocarbons. The halide-hydride exchange represents a biochemical equivalent for the reduction of halocarbons by traditional synthetic reagents like silanes (R3Si-H) and stannanes (R3Sn-H). High precision thermochemical calculations (CBS-QB3) reveal the carbon-hydrogen bond dissociation energy of NADH (70.8 kcal·mol-1) to be lower than that of stannane (SnH4: 78.1 kcal·mol-1), approaching that of the elusive plumbane (PbH4: 68.9 kcal·mol-1). The ready synthetic accessibility of NADH models, their low carbon-hydrogen bond dissociation energy, and their dehalogenation activity in the presence of air and moisture recommend these compounds as substitutes for the air-sensitive or toxic metal hydrides currently employed in synthesis.

Reductive dehalogenation of DDT with folate models: Formation of the DDT metabolite spectrum under biomimetic conditions.

The insecticide DDT is an omnipresent environmental contaminant and an ongoing toxicological concern. The recent discovery that methylenetetrahydrofolate (MTHF) models are capable of reducing a range of halocarbons to hydrocarbons under biomimetic conditions has prompted us to investigate the possible role of MTHF in the metabolism of DDT. We now report that the reaction of MTHF models with DDT produces no less than five known in vivo metabolites of DDT, namely DDD, DDE, DDMU, DBP, and DDM. The capability of the MTHF models to produce the full spectrum of known DDT dehalogenation products is strong evidence that the mechanistically obscure metabolism of DDT may involve MTHF. The findings also suggest that DDT should be capable of disrupting folate-dependent pathways.

Nature's hydrides: rapid reduction of halocarbons by folate model compounds.

Halocarbons R-X are reduced to hydrocarbons R-H by folate model compounds under biomimetic conditions. The reactions correspond to a halide-hydride exchange with the methylenetetrahydrofolate (MTHF) models acting as hydride donors. The MTHF models are also functional equivalents of dehalohydrogenases but, unlike these enzymes, do not require a metal cofactor. The reactions suggest that halocarbons have the potential to act as endocrinological disruptors of biochemical pathways involving MTHF. As a case in point, we observe the rapid reaction of the MTHF models with the inhalation anaesthetic halothane. The ready synthetic accessibility of the MTHF models as well as their dehalogenation activity in the presence of air and moisture allow for the remediation of toxic, halogenated hydrocarbons.

Neonatal cleft lip and cleft palate repair.

Facial clefting is one of the most common birth defects and having a child born with this defect can be a devastating experience for parents and family members. Until recently, repair of cleft lip and palate deformities was deferred until the infant had reached 10 weeks of age, 10 pounds in weight, and a hemoglobin level of 10 gm per 100 mL. This criteria eliminated neonates 28 days of age or younger from the possibility of early repair. Waiting until these criteria were achieved often caused problems with parent-infant bonding and infant growth and development. Advances in neonatology and pediatric anesthesia now have made it possible to perform cleft surgery during the neonatal period. This article discusses the anatomy and embryology of cleft deformities and how cleft repair surgery now can be performed on the neonate.

Effects of University of Wisconsin and lactated Ringer's solutions to ischemia-reperfusion injury in isolated cremaster flap.

Ischemia-reperfusion (I/R) injury is a topic that has been much-discussed by various researchers during the last decade in plastic surgery. Though much progress has occurred, the problem is not totally solved yet. In particular, the pathophysiology of reperfusion injury in skeletal muscle has not been clearly elucidated. The aims of this study are to assess the effects of a variety of perfusants on the microcirculation after reperfusion injury and to better understand the pathophysiology of reperfusion injury. Isolated cremaster flaps were performed in 44 rats, preserving the femoral artery and vein in order to cannulate with microtubes. There were 2 control and 2 experiment groups. In one of the control groups and in both experimental groups, 2 h of ischemia were applied by clamping the iliac vessels. Immediately after this, the muscle was locally perfused and washed with lactated Ringer's (LR) and University of Wisconsin (UW) solutions, given from the femoral artery and drained by the femoral vein in the two respective experimental groups. The effects of these solutions to I/R injury were shown at the microcirculatory level via measuring and determining preischemic and postischemic diameters of arterioles and venules, tissue perfusion, capillary density, velocity of red blood cells, and leukocyte sticking. Both tested perfusion solutions were found to be harmful in all parameters. This study demonstrates that both LR and UW solutions aggravate I/R injury.

Surgical treatment of nasal hemangiomas.

The treatment of nasal hemangiomas continues to be controversial. The authors' experience with early surgical treatment of nasal hemangiomas is presented. This retrospective study includes 11 patients. Surgical intervention consisted of excision of the nasal hemangioma and reconstruction by local tissue transfer or rearrangement. Age at surgery ranged from 10 months to 6.5 years (mean age, 2.2 years). All patients have acceptable nasal contour and have demonstrated excellent nasal growth. The authors' experience demonstrates that early surgical intervention is an acceptable alternative for the management of nasal hemangiomas.