Encapsulation of proteins in transparent porous silicate glasses prepared by the sol-gel method.

Novel sol-gel synthetic techniques were used to immobilize copper-zinc superoxide dismutase (CuZnSOD), cytochrome c, and myoglobin (Mb) by encapsulation in stable, optically transparent, porous silica glass matrices under mild conditions such that the biomolecules retained their characteristic reactivities and spectroscopic properties. The resulting glasses allowed transport of small molecules into and out of the glasses at reasonable rates but nevertheless retained the protein molecules within their pores. Chemical reactions of the immobilized proteins could be monitored by means of changes in their visible absorption spectra. Silica glasses containing the immobilized proteins were observed to have similar reactivities and spectroscopic properties to those found for the proteins in solution. For example, encapsulated CuZnSOD was demetallated and remetallated, encapsulated ferricytochrome c was reduced and then reoxidized, and encapsulated met Mb was reduced to deoxy Mb and then reacted either with dioxygen to make oxy Mb or with carbon monoxide to make carbonyl Mb.

A molecular nanocap activated by superparamagnetic heating for externally stimulated cargo release.

A novel thermoresponsive snaptop for stimulated cargo release from superparamagnetic iron oxide core - mesoporous silica shell nanoparticles based on a [2 + 4] cycloreversion reaction (retro-Diels Alder reaction) is presented. The non-invasive external actuation through alternating magnetic fields makes this material a promising candidate for future applications in externally triggered drug delivery.

Magnetic field activated drug delivery using thermodegradable azo-functionalised PEG-coated core-shell mesoporous silica nanoparticles.

Core-shell Fe3O4@SiO2 mesoporous silica nanoparticles coated with a new thermodegradable polymer allowed the release of a model drug through heating caused by a high frequency oscillating magnetic field. The thermodegradable polymer was made of poly(ethylene glycol) (PEG) functionalised with azo bonds that break with an elevation of temperature.

Association between lower optic nerve laser Doppler blood volume measurements and glaucomatous visual field progression.

AIM: To perform a preliminary assessment of the relation between optic nerve circulatory parameters and glaucomatous visual field progression. METHODS: This study included 29 eyes of 23 patients with open angle glaucoma that had typical glaucomatous nerve fibre bundle visual field defects and increased cup to disc ratios. Laser Doppler flowmetry (Oculix) was used to measure relative optic nerve blood volume (Vol), velocity (Vel) and flow in the superior temporal (ST) and inferior temporal (IT) neuroretinal rim of the optic nerve. After blood flow measurements patients were followed for 6-62 months (mean 33 (SD 17) months) and 2-11 Humphrey visual fields (4.7 (2.6) fields) were obtained. Progression of glaucoma was assessed by the slope of the corrected pattern standard deviation (CPSD) values versus time, which was calculated manually for each eye using regression analysis. RESULTS: A significant negative correlation was observed between Vol in the IT rim and the CPSD slope (r=-0.56, p=0.002); patients with lower Vol tended to show faster progression of glaucomatous field damage than those with higher Vol. When the eyes were arbitrarily divided into two groups according to lower Vol (0.32 (0.06) arbitrary units, AU, n=15) or higher Vol (0.49 (0.06) AU, n=14), those with lower Vol had significantly worse mean CPSD slopes (0.50 (0.48) dB/year) than those with higher Vol (-0.67 (1.38) dB/year; Student's t test, p=0.009). CONCLUSIONS: In the IT rim, the area most prone to develop glaucomatous field damage, lower Vol is associated with subsequently faster CPSD progression. These measurements suggest that circulatory abnormalities may have a role in the development of glaucoma.

Effect of hypothermia, dichloroacetate, and deferoxamine in the treatment for cortical edema and functional recovery after experimental cortical impact in the rat.

OBJECTIVE: To investigate the effects of hypothermia alone or in combination with dichloroacetic acid (DCA) and/or deferoxamine (DFO) in reducing cortical edema (CE) and improving neurologic functional recovery after moderate closed and head trauma with controlled cortical impact (CCI). METHODS: Anesthetized rats were randomized to receive right parietal moderate CCI (impact depth 2 mm, speed 3.5 m/sec) or sham operations. Immediately after trauma, the animals underwent selective brain cooling to 30 degrees C (temporalis muscle temperatures). Ten minutes after trauma, the randomized animals received intraperitoneal doses of DCA (25 mg/kg), DFO (50 mg/kg), both DCA and DFO, or equivolume normal saline. For evaluation of cortical edema, some animals (n = 42) were sacrificed 4 hours after trauma and cortical specific gravity (SpG) was determined gravimetrically. The other animals (n = 47) were evaluated for functional recovery beginning 6 days posttrauma. Neurobehavioral performance was assessed in the Morris water maze. RESULTS: Cortical edema was significantly less in the animals treated with hypothermia (SpG = 1.041 +/- 0.001, p < 0.05) compared with the untreated traumatized animals (SpG = 1.037 +/- 0.001). Combination treatment with hypothermia and drug treatment did not reduce cortical edema when compared with no treatment. Hypothermia with and without drug treatment did not improve neurobehavioral performance when compared with no treatment. CONCLUSIONS: In this pilot study with a relatively small sample size, hypothermia alone significantly reduced post-CCI cortical edema as measured by SpG. Hypothermia combined with drug treatment did not reduce posttraumatic cortical edema. Hypothermia with and without drug therapy did not improve functional neurologic recovery in the rats subjected to CCI.

Ischemic preconditioning improves the survival of skin and myocutaneous flaps in a rat model.

Inadequate blood supply of pedicle flaps results in partial necrosis, and prolonged ischemia during free-tissue transfer can result in partial or complete flap necrosis. Recent research in the field of cardiovascular surgery has shown that ischemic preconditioning (repeated brief episodes of coronary artery occlusion followed by reperfusion) improves myocardial muscle survival when the heart is subsequently subjected to prolonged ischemia. Preconditioning of skin or myocutaneous flaps as either pedicle or free flap models has never been studied. The goal of this investigation was to measure the effect of ischemic preconditioning on myocutaneous and skin flap survival areas and total necrosis rates after variable periods of global ischemia. In 220 rats, 100 transverse rectus abdominis myocutaneous flaps and 120 dorsal cutaneous flaps were randomized into treatment and control groups. The treatment flaps underwent preconditioning by three cycles of 10 minutes of pedicle clamping followed by 10 minutes of reperfusion for a total preconditioning period of 1 hour. The control flaps were perfused without clamping for 1 hour. Both control and treatment flaps then underwent global ischemia for 0, 2, 4, 6, 10, or 14 hours by pedicle clamping. Flap survival area was measured on the fifth postoperative day. Statistical analysis was performed with analysis of variance, student's t tests, and probit analysis. Preconditioning improved survival areas of pedicle myocutaneous flaps (0-hour group) from 47 +/- 16 percent (mean percent area surviving +/- SD) to 63 +/- 5 percent. This difference was statistically significant (t test, p < 0.04). There was no statistically significant improvement in pedicle skin flap survival. For free flap models (flaps undergoing global ischemia), preconditioning increased the survival areas of skin and myocutaneous flaps (analysis of variance, p < 10(-5)). For the skin flap model, statistical significance of the survival area difference was reached at 6, 10, and 14 hours of ischemia (t test, p < 10(-4)). The magnitude of this effect was higher in the myocutaneous flap model and reached statistical significance at 2, 4, 6, and 10 hours of ischemia (p < 10(-3)). Preconditioned flap survival areas were increased by two to five times that of non-preconditioned flaps at these ischemia times. Preconditioning lowered total necrosis rates at all ischemia times for both flap models. The critical ischemia time when 50 percent of skin flaps became totally necrotic (CIT50) improved from 6.9 to 12.4 hours by preconditioning. Similarly, preconditioning improved the CIT50 of myocutaneous flaps from 3.6 to 9.2 hours. For the first time, statistically significant improvements of partial necrosis areas and total necrosis rates have been demonstrated through intraoperative ischemic preconditioning of skin and myocutaneous flaps. In clinical practice, application of this technique may lead to improved survival during pedicled or free transfer of myocutaneous flaps and free transfer of skin flaps.

TRAM flap perforator ligation and the delay phenomenon: development of an endoscopic/laparoscopic delay procedure.

Despite its versatility in breast reconstruction, the TRAM flap is at times subject to ischemic compromise, especially in certain high risk populations. A preoperative delay procedure can decrease the likelihood of TRAM flap failure or fat necrosis, but the required extent of this delay procedure is not clearly defined. In an attempt to augment flap vascularity while reducing surgical dissection and morbidity, six distinct delay procedures and a nondelayed control were compared in a rat TRAM flap model (n = 8 for all groups). An important feature that was incorporated into several groups was the ligation of the contralateral rectus perforators through minimal skin incisions (endoscopic analogy, groups 4 to 7). The most effective delay procedure was the combination of contralateral rectus perforator ligation and ipsilateral dominant pedicle ligation (group 7), which was achieved with two minimal skin incisions and no significant flap undermining. This procedure reduced the flap necrosis from 63.2 +/- 5.8 percent (control) to 13.5 +/- 3.3 percent (p < 0.001). After completion of the animal studies, clinical application of a "minimally invasive" TRAM flap delay procedure was then undertaken in eight high risk patients with only modest ischemic compromise. Although the clinical experience is too early to draw definite conclusions, we feel that "endoscopic delay" has potential as a modality that will increase flap vascularity but minimize the morbidity of the preliminary procedure.

Relative rates of absorption of fluid and protein from the peritoneal cavity in cats.

The relative rates of fluid and protein absorption from the peritoneal cavity of anesthetized cats were measured over 6 hours at an intraperitoneal pressure of 15 mm Hg and with intraperitoneal protein concentrations from 1-8 g%. The fractional absorption rates of fluid and protein did not change significantly over the 6 hours and were not significantly different from each other within each one hour period. In addition both fractional absorption rates were unaffected by the protein concentration of the fluid within the peritoneal cavity. Although the absolute rate of absorption is greatly increased by elevation of the intraperitoneal pressure, these data indicate that the process remains iso-oncotic as would be expected for lymphatic rather than transcapillary absorption.

Nanovalve activation by surface-attached photoacids.

Proton transfer caused by excitation of a photoacid attached to the surface of a mesoporous silica nanoparticle activates a nanovalve and causes release of trapped molecules. The protonation of an aniline-based stalk releases a noncovalently bound cyclodextrin molecule that blocked a pore. The results show that pH-responsive molecular delivery systems can be externally controlled using light.

Analysis of long-term outcomes for combined pars plana vitrectomy (PPV) and glaucoma tube shunt surgery in eyes with advanced glaucoma.

PURPOSE: To analyze 12- and 24-month visual acuity, intraocular pressure, and complications associated with combined pars plana vitrectomy (PPV) and glaucoma tube shunt placement in eyes with glaucoma. PATIENTS AND METHODS: A retrospective chart review was performed of patients with advanced glaucoma who underwent combined PPV and tube shunt surgery from 2006 to 2010. A minimum of 12 months of follow-up was required for their inclusion in the study. Visual acuity, intraocular pressure, complications, and number of glaucoma medications at 1 and 2 years postoperatively were analyzed. RESULTS: Twenty-eight eyes met the inclusion and exclusion criteria. Baseline visual acuity was 20/200 or worse in 14/28 eyes (50.0%) and 20/40 or better in 2/28 eyes (7.1%). Visual acuity remained 20/200 or worse in 50.0% (P=0.921) and 44.4% (P=0.973) of eyes after 1 and 2 years postoperatively, respectively. At baseline, the mean intraocular pressure was 30.4 mm Hg. There was significant improvement in mean IOP at 1 year (14.7 mm Hg, P=0.001) and at 2 years (15.2 mm Hg, P=0.001) postoperatively. Baseline number of glaucoma medications averaged 3.0±1.09 (SD), and improved to 1.8±1.28 (SD) at 1 year (P=0.0002) and to 1.4±1.33 at 2 years (P<0.0001) postoperatively. CONCLUSION: In this retrospective interventional case series, surgical management of advanced glaucoma with a combination of PPV and glaucoma tube shunt resulted in significantly reduced IOP and glaucoma medications at 1 and 2 years postoperatively.

Clinical integration and nursing leadership across an integrated delivery system.

As new health systems struggle to combine in today's challenging health care market, mechanisms that facilitate and enhance integration become increasingly important. This article describes the use of clinical paths in an integrated delivery system (IDS) as a methodology to establish a single standard of high-quality care. Through education and sharing of staff development resources across the IDS, the system nurse executive at one large IDS promotes professional practice. As clinical paths are developed across the system, the best clinical practice is put to paper, providing a framework for outcome-driven care. The nurse manager assesses staff's use of clinical paths as an evaluation of their skills and competency and to identify new educational and growth opportunities.

In-situ gas-phase luminescence and time-of-flight mass spectroscopic detection of photofragments during photochemical synthesis of copper particles from bis(tert-butylacetoacetato)copper.

During the 308 nm laser-driven photochemical synthesis of Cu particles from bis(tert-butylacetoacetato)copper, gas-phase photogenerated intermediates are identified by luminescence and time-of-flight mass spectroscopies. Pure Cu deposits are obtained as homogeneous, granular 200 nm particles. In the gas phase, luminescent photoproducts are observed and atomic Cu, Cu2, and dissociated ligand are identified spectroscopically. In addition, mass spectroscopy identifies Cu atoms, the dissociated ligand, a monoligated complex, and fragments of the ligands. The implications of the photofragmentation that produces copper atoms and dimers for the laser-assisted production of the Cu deposits are discussed.

Noradrenergic control of blood vessels in the premature lamb fetus.

Experiments were conducted with fetal lambs of 113-120 days gestation (0.8 term) to assess the integrity of adrenergic neurotransmission at the level of the blood vessels. Regional blood flow and the distribution of blood from the inferior vena cava were compared when the arterial pressure was increased either by an infusion of exogenous noradrenaline or when tyramine was used to evoke a local release of the neurotransmitter. Most vascular beds perfused via the descending aorta were constricted to a similar extent by both drugs although the renal circulation did not respond to tyramine. Noradrenaline increased the distribution of blood from the inferior vena cava to the fetal lungs and both drugs increased placental blood flow. These data indicate that mechanisms for effective adrenergic control of vascular are developed in many organs of the premature lamb fetus by 0.8 of term.

Control of ascites absorption in anesthetized cats: effects of intraperitoneal pressure, protein, and furosemide diuresis.

There is considerable evidence that fluids are removed from the peritoneal cavity by drainage into lymphatics lining the surface of the diaphragm, but there is little quantitative information on the rate of reabsorption as affected by conditions which exist in cirrhotic ascites. In the present study a plethysmographic technique was utilized to record the rate of absorption of fluid from the peritoneal cavity of anesthetized cats. The results of studies in 33 cats showed that the rate of fluid absorption from the peritoneal cavity was directly proportional to the intraperitoneal pressure regardless of whether the intraperitoneal fluid was free from protein or contained a protein concentration equivalent to that of plasma. Fluid was absorbed with a protein concentration equivalent to that present in the peritoneal cavity. Thus it is apparent that the intraperitoneal pressure is an important factor controlling the accumulation of ascitic fluid but the protein concentration of the intraperitoneal fluid does not affect the rate of reabsorption. In addition, marked diuresis induced by intravenous furosemide does not appear to mobilize ascites by an effect on the reabsorption process.