BPC 157 Rescued NSAID-cytotoxicity Via Stabilizing Intestinal Permeability and Enhancing Cytoprotection.

The stable gastric pentadecapeptide BPC 157 protects stomach cells, maintains gastric integrity against various noxious agents such as alcohol, nonsteroidal anti-inflammatory drugs (NSAIDs), and exerts cytoprotection/ adaptive cytoprotection/organoprotection in other epithelia, that is, skin, liver, pancreas, heart, and brain. Especially BPC 157 counteracts gastric endothelial injury that precedes and induces damage to the gastric epithelium and generalizes "gastric endothelial protection" to protection of the endothelium of other vessels including thrombosis, prolonged bleeding, and thrombocytopenia. In this background, we put the importance of BPC 157 as a possible way of securing GI safety against NSAIDs-induced gastroenteropathy since still unmet medical needs to mitigate NSAIDs-induced cytotoxicity are urgent. Furthermore, gastrointestinal irritants such as physical or mental stress, NSAIDs administration, surfactants destroyer such as bile acids, alcohol can lead to leaky gut syndrome through increasing epithelial permeability. In this review article, we described the potential rescuing actions of BPC 157 against leaky gut syndrome after NSAIDs administration for the first time.

Lung T lymphocyte trafficking and activation during ischemic acute kidney injury.

Despite advances in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely owing to extrarenal organ dysfunction. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that facilitate organ crosstalk and induce caspase-dependent lung apoptosis and injury through a TNFR1-dependent pathway. Given that T lymphocytes mediate local IRI in the kidney and are known to drive TNFR1-mediated apoptosis, we hypothesized that T lymphocytes activated during kidney IRI would traffic to the lung and mediate pulmonary apoptosis during AKI. In an established murine model of kidney IRI, we identified trafficking of CD3+ T lymphocytes to the lung during kidney IRI by flow cytometry and immunohistochemistry. T lymphocytes were primarily of the CD3+CD8+ phenotype; however, both CD3+CD4+ and CD3+CD8+ T lymphocytes expressed CD69 and CD25 activation markers during ischemic AKI. The activated lung T lymphocytes did not demonstrate an increased expression of intracellular TNF-α or surface TNFR1. Kidney IRI induced pulmonary apoptosis measured by caspase-3 activation in wild-type controls, but not in T cell-deficient (T(nu/nu)) mice. Adoptive transfer of murine wild-type T lymphocytes into T(nu/nu) mice restored the injury phenotype with increased cellular apoptosis and lung microvascular barrier dysfunction, suggesting that ischemic AKI-induced pulmonary apoptosis is T cell dependent. Kidney-lung crosstalk during AKI represents a complex biological process, and although T lymphocytes appear to serve a prominent role in the interorgan effects of AKI, further experiments are necessary to elucidate the specific role of activated T cells in modulating pulmonary apoptosis.

Experimental evaluation of an adaptive Joule-Thomson cooling system including silicon-microfabricated heat exchanger and microvalve components.

This article reports the evaluation of a Joule-Thomson (JT) cooling system that combines two custom micromachined components-a Si/glass-stack recuperative heat exchanger and a piezoelectrically actuated expansion microvalve. With the microvalve controlling the flow rate, this system can modulate cooling to accommodate varying refrigeration loads. The perforated plate Si/glass heat exchanger is fabricated with a stack of alternating silicon plates and Pyrex glass spacers. The microvalve utilizes a lead zirconate titanate actuator to push a Si micromachined valve seat against a glass plate, thus modulating the flow passing through the gap between the valve seat and the glass plate. The fabricated heat exchanger has a footprint of 1 × 1 cm(2) and a length of 35 mm. The size of the micromachined piezoelectrically actuated valve is about 1 × 1 × 1 cm(3). In JT cooling tests, the temperature of the system was successfully controlled by adjusting the input voltage of the microvalve. When the valve was fully opened (at an input voltage of -30 V), the system cooled down to a temperature as low as 254.5 K at 430 kPa pressure difference between inlet and outlet at steady state and 234 K at 710 kPa in a transient state. The system provided cooling powers of 75 mW at 255 K and 150 mW at 258 K. Parasitic heat loads at 255 K are estimated at approximately 700 mW.

Protective effects of triamcinolone acetonide upon the upregulation and phosphorylation of GAP 43 in an animal model of retinopathy of prematurity.

PURPOSE: The aim of the current study was to investigate the effects of triamcinolone acetonide (TA) upon the expression and phosphorylation of growth-associated protein 43 (GAP 43) in the retinas of oxygen-induced retinopathy (OIR) rats. METHODS: Oxygen-induced retinopathy was induced by exposing Sprague-Dawley rats to hyperoxia (80% oxygen) from postnatal (P) days 2-14 and then returning the rats to normoxic conditions. Triamcinolone acetonide or a conditioned saline (control) was injected intravitreally into the right or left eye, respectively, of OIR rats at P15. We then assessed the molecular and histological changes in the expression of GAP 43 and phospho-GAP 43 in OIR and control rat retinas, and also after treatment with TA by RT-PCR, Western blotting and immunohistochemistry. RESULTS: Growth-associated protein 43 mRNA levels were found to be increased by 1.6-fold (p=0.001, n=5) in the retinas of P18 OIR rats compared with the control rats. The protein levels of GAP 43 and phospho-GAP43 were found to be elevated in the retina of P18 OIR rats (2.40- and 2.39-fold greater than each control, p<0.001, n=5, respectively). Immunoreactivities of GAP 43 and phospho-GAP 43 were stronger in the inner plexiform layer in OIR rat retinas compared with the control. However, treatment with TA attenuated GAP 43 and phospho-GAP 43 upregulation in the OIR retinas. CONCLUSION: Our results indicate that GAP 43 and phospho-GAP 43 participate in retinal (potentially pathologic) changes following oxygen-induced damage. Triamcinolone acetonide protects the retinal damage in relatively hypoxic retinas of OIR rats. Therefore, TA treatment does not induce the expression and phosphorylation of GAP 43 in OIR rat retinas.

A low power, microvalve regulated architecture for drug delivery systems.

This paper describes an actively-controlled architecture for drug delivery systems that offers high performance and volume efficiency through the use of micromachined components. The system uses a controlled valve to regulate dosing by throttling flow from a mechanically pressurized reservoir, thereby eliminating the need for a pump. To this end, the valve is fabricated from a glass wafer and silicon-on-insulator wafer for sensor integration. The valve draws a maximum power of 1.68 µW| (averaged over time); with the existing packaging scheme, it has a volume of 2.475 cm3. The reservoirs are assembled by compressing polyethylene terephthalate polymer balloons with metal springs. The metal springs are fabricated from Elgiloy® using photochemical etching. The springs pressurize the contents of 37 mLchambers up to 15 kPa. The system is integrated with batteries and a control circuit board within a 113 cm3 metal casing. This system has been evaluated in different control modes to mimic clinical applications. Bolus deliveries of1.5 mL have been regulated as well as continuous flows of 0.15 mL/day with accuracies of 3.22%. The results suggest that this device can be used in an implant to regulate intrathecal drug delivery

Removal of cationic heavy metal from aqueous solution by activated carbon impregnated with anionic surfactants.

To increase their capacity to adsorb heavy metals, activated carbons were impregnated with the anionic surfactants sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS), or dioctyl sulfosuccinate sodium (DSS). Surfactant-impregnated activated carbons removed Cd(II) at up to 0.198 mmol g(-1), which was more than an order of magnitude better than the Cd(II) removal performance of activated carbon without surfactant (i.e., 0.016 mmol g(-1)) even at optimal pH (i.e., pH 6). The capacity of the activated carbon to adsorb Cd(II) increased in proportion to the quantity of surfactant with which they were impregnated. The kinetics of the adsorption of Cd(II) onto the surfactant-impregnated activated carbon was best described by a pseudo-second-order model, and was described better by the Freundlich adsorption isotherm than by the Langmuir isotherm. The surface charge of activated carbon was negative in all pH ranges tested (2-6). These results indicate that surface modification with anionic surfactant could be used to significantly enhance the capacity of activated carbon to adsorb cations.

Mathematical evaluation of activated carbon adsorption for surfactant recovery in a soil washing process.

The performances of various soil washing processes, including surfactant recovery by selective adsorption, were evaluated using a mathematical model for partitioning a target compound and surfactant in water/sorbent system. Phenanthrene was selected as a representative hazardous organic compound and Triton X-100 as a surfactant. Two activated carbons that differed in size (Darco 20-40 mesh and >100 mesh sizes) were used in adsorption experiments. The adsorption isotherms of the chemicals were used in model simulations for various washing scenarios. The optimal process conditions were suggested to minimize the dosage of activated carbon and surfactant and the number of washings. We estimated that the requirement of surfactant could be reduced to 33% of surfactant requirements (from 265 to 86.6g) with a reuse step using 9.1g activated carbon (>100 mesh) to achieve 90% removal of phenanthrene (initially 100mg kg-soil(-1)) with a water/soil ratio of 10.

Estimation of direct-contact fraction for phenanthrene in surfactant solutions by toxicity measurement.

The toxicity of solutions containing nonionic surfactants Tween 80, Brij 35 and/or phenanthrene to Pseudomonas putida ATCC 17484 was investigated. The fraction of direct contact between micellar-phase phenanthrene and bacterial cell surface was estimated by using the toxicity data and a mathematical model. The mathematical model was used to calculate phenanthrene concentration in the micellar phase and aqueous pseudophase separately. The first-order death rate constant increased from 0.088+/-0.016 to 0.25+/-0.067 h(-1) when the phenanthrene concentration was increased from 0 to 5.17 x 10(-6)M (equals water solubility). The intrinsic toxicity of surfactant was higher in Brij 35 than in Tween 80. When phenanthrene concentration was increased to 9.7 x 10(-5)M in surfactant solutions, the death rate constant increased to 1.8 +/- 0.024 and 0.41 +/- 0.088 h(-1) for 8.4 x 10(-4)M Brij 35 and 7.6 x 10(-4)M Tween 80. The direct-contact fraction was 0.083 and 0.044 for Brij 35 and Tween 80, respectively, under these conditions using exponential model. The toxicity increased with increasing phenanthrene concentration at a fixed surfactant concentration. The toxicity decreased with increasing the surfactant concentration at a fixed phenanthrene concentration due to decreased contact of bacteria with phenanthrene present in the interior of surfactant micelles.

Selective adsorption of phenanthrene dissolved in surfactant solution using activated carbon.

Selective adsorption of a hazardous hydrophobic organic compound (HOC) by activated carbon as a means of recovering surfactants after a soil washing process was investigated. As a model system, phenanthrene was selected as a representative HOC and Triton X-100 as a nonionic surfactant. Three activated carbons that differed in size (Darco 20-40 (D20), 12-20 (D12) and 4-12 (D4) mesh sizes) were used in adsorption experiments. Adsorption of surfactant onto activated carbon showed a constant maximum above the critical micelle concentration, which were 0.30, 0.23, 0.15 g g(-1) for D20, D12, and D4, respectively. Selectivity for phenanthrene to Triton X-100 was much higher than 1 over a wide range of activated carbon doses (0-6 g l(-1)) and initial phenanthrene concentrations (10-110 mg l(-1)). Selectivity generally increased with decreasing particle size, increasing activated carbon dose, and decreasing initial concentration of phenanthrene. The highest selectivity was 74.9, 57.3, and 38.3 for D20, D12, and D4, respectively, at the initial conditions of 10 mg l(-1) phenanthrene, 5 g l(-1) Triton X-100 and 1g l(-1) activated carbon. In the case of D20 at the same conditions, 86.5% of the initial phenanthrene was removed by sorption and 93.6% of the initial Triton X-100 remained in the solution following the selective adsorption process. The results suggest that the selective adsorption by activated carbon is a good alternative for surfactant recovery in a soil washing process.

Biodegradation of phenanthrene in soil-slurry systems with different mass transfer regimes and soil contents.

The effect of soil contents and mass transfer rates on soil bioremediation was investigated. Phenanthrene, a 3-ring polycyclic aromatic hydrocarbon (PAH), was chosen as a model target compound. The biodegradation tests were performed in soil-slurry systems at two distinct mass transfer rates: fast in flasks tests at 150 rpm and slow in roller-bottle tests at 2 rpm. The rate of phenanthrene biodegradation was similar at low soil content (2 wt.%) in both slurry systems, but the rates at high soil contents (6 and 18 wt.%) were higher in the roller-bottle tests. The maximum utilization rate constant for sorbed-phase biodegradation obtained from curve fitting using a mathematical model was decreased in the flask tests with increasing soil content, while not decreased in the roller-bottle tests.

Degradation of tetracyanonickelate (II) by Cryptococcus humicolus MCN2.

A new yeast strain capable of degrading free and metallocyanides was isolated from coke-plant wastewater. The isolated strain designated MCN2 was identified as Cryptococcus humicolus by 26S rDNA sequencing and phylogenetic analysis. During growth of the isolate with KCN as a sole nitrogen source, formamide and formic acid were found as transient intermediates by [(13)C]nuclear magnetic resonance analysis and ammonia accumulated as a final product in the culture medium. The strain MCN2 could degrade high concentrations of tetracyanonickelate (II) (K(2)Ni(CN)(4), TCN) up to 65 mM CN within 60 h when a sufficient amount of glucose was supplied as a carbon source. The maximal degradation rate of TCN was 2.5 mM CN h(-1) at the initial concentration of 51 mM CN.