A Generalized System for Photo-Responsive Membrane Rupture in Polymersomes

Polymersomes are vesicles whose membranes are comprised of self-assembled block co-polymers. We recently showed that co-encapsulating conjugated multi-porphyrin dyes in a polymersome membrane with ferritin protein in the aqueous lumen confers photo-lability to the polymersome. In the present study, we illustrate that the photo-lability can be extended to vesicles containing dextran, an inert and inexpensive polysaccharide, as the luminal solute. Here we explore how structural features of the polymersome/porphyrin/dextran composite affect its photo-response. Increasing dextran molecular weight, decreasing block copolymer molecular weight, and altering fluorophore-membrane interactions results in increasing the photo-responsiveness of the polymersomes. Amphiphilic interactions of the luminal encapsulant with the membrane coupled with localized heat production in the hydrophobic bilayer likely cause differential thermal expansion in the membrane and the subsequent membrane rupture. This study suggests a general approach to impart photo-responsiveness to any biomimetic vesicle system without chemical modification, as well as a simple, bio-inert method for constructing photo-sensitive carriers for controlled release of encapsulants.     

Methanol synthesis over Cu/SiO2 catalysts

The rates of CO and CO/CO₂ hydrogenation at 4.2 MPa and 523 K are reported for a series of Cu/SiO₂ catalysts containing 2 to 88 wt.% Cu. These catalysts were prepared on a variety of silica sources using several different Cu deposition techniques. In CO/CO₂ hydrogenation, the rate of methanol formation is proportional to the exposed Cu surface area of the reduced catalyst precursor, as determined by N₂O frontal chromatography. The observed rate, 4.2×10^–3 mole CH₃OH/Cu site-sec, is within a factor of three of the rates reported by others over Cu/ZnO and Cu/ZnO/Al₂O₃ catalysts under comparable conditions. These results suggest that the ZnO component is only a moderate promoter in methanol synthesis. Hydrogenation of CO over these catalysts also gives methanol with high selectivity, but the synthesis rate is not proportional to the Cu surface area. This implies that another type of site, either alone or in cooperation with Cu, is involved in the synthesis of methanol from CO.     

Long wavelength GRIN-SCH MQW lasers incorporating graded GaAlInAs confinement layers

We report the growth and characterisation of the first GaAllnAs based GRIN-SCH MQW lasers operating at 1.3 and 1.6μm. In these devices, GaAllnAs barriers and either GalnAs or GaAllnAs wells have been used for the 1.6 and 1.3μm lasers, respectively, together with true continuously graded composition GaAlInAs regions for the confinement layers. The excellent structural quality of the active and confinement regions and control of wavelength uniformity has been confirmed. Buried ridge lasers fabricated from the GRIN-SCH MQW wafers lased at 1.3 and 1.6μm with CW threshold currents of 65 and 30 mA, respectively.     

Thermostable archaeal O6-alkylguanine-DNA alkyltransferases

Archaea represent some of the most ancient organisms on earth, and they have relatively uncharacterized DNA repair processes. We now show, using an in vitro assay, that extracts of two Crenarchaeota (Sulfolobus acidocaldarius and Pyrobaculum islandicum) and two Euryarchaeota (Pyrococcus furiosus and Thermococcus litoralis) contain the DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase). The ATase activities found in the archaea were extremely thermostable, with half-lives at 80 degreesC ranging from 0.5 hr (S. acidocaldarius) to 13 hr (T. litoralis). The temperature optima of the four proteins ranged from approximately 75 to approximately 100 degreesC, although activity was seen at 37 degreesC, the temperature optimum of the Escherichia coli and human ATases. In all cases, preincubaton of extracts with a short oligonucleotide containing a single O6-methylguanine residue caused essentially complete loss of ATase activity, suggesting that the alkylphosphotriester-DNA alkyltransferase activity seen in some prokaryotes is not present in Archaea. The ATase from Pyrobaculum islandicum had an apparent molecular mass of 15 kDa, making it the smallest of these proteins so far described. In higher organisms, ATase is responsible for the repair of toxic and mutagenic O6-alkylguanine lesions in alkylated DNA. The presence of ATase in these primitive organisms therefore suggests that endogenous or exogenous exposure to agents that generate appropriate substrates in DNA may be an early event in evolution.     

Preseasonal intranasal immunotherapy in birch-alder allergic rhinitis. A double-blind study

A double-blind, placebo-controlled study was carried out to test the clinical efficacy and safety of local nasal immunotherapy (LNIT) in powder form. Twenty-two patients suffering from allergic rhinitis strictly associated with early spring symptoms, with positive skin prick tests and RAST for birch-alder, all responders to a specific nasal provocation test (NPT), received randomly active or placebo treatment for 4 months. Immunotherapy consisted of administration of a set of capsules containing progressively increasing amounts of birch (Betula pendula) and speckled alder (Alnus incana) allergens in powder form with controlled granulometry. The active (birch-alder) and placebo (lactose) group completed the treatment according to a similar schedule. During the pollen season (March-April), the patients who took the active treatment reported less sneezing and rhinorrhea than the placebo group, on the basis of a symptoms score, and the differences were statistically significant; the need for drugs (terfenadine) was also significantly reduced. These findings agreed well with the results of specific NPT after the treatment; only patients in the active group had a higher threshold dose of nasal specific reactivity to birch-alder allergens than in tests before the LNIT.     

The role of angiotensin AT1 receptors in the diuretic, natriuretic, kaliuretic and blood pressure responses induced by angiotensin II activation of the median preoptic nucleus in conscious rats

We determined the effects of two classical angiotensin II (ANG II) antagonists, [Sar1, Ala8]-ANG II and [Sar1, Thr8]-ANG II, and losartan (a nonpeptide and selective antagonist for the AT1 angiotensin receptors) on diuresis, natriuresis, kaliuresis and arterial blood pressure induced by ANG II administration into the median preoptic nucleus (MnPO) of male Holtzman rats weighing 250-300 g. Urine was collected in rats submitted to a water load (5% body weight) 1 h later. The volume of the drug solutions injected was 0.5 microliters over 10-15 s. Pre-treatment with [Sar1, Ala8]-ANG II (12 rats) and [Sar1, Thr8]-ANG II (9 rats), at the dose of 60 ng reduced (13.7 +/- 1.0 vs 11.0 +/0 1.0 and 10.7 +/0 1.2, respectively), whereas losartan (14 rats) at the dose of 160 ng totally blocked (13.7 +/- 1.0 vs 7.6 +/- 1.5) the urine excretion induced by injection o 12 ng of ANG II (14 rats). [Sar1, Ala8]-ANG II impaired Na+ excretion (193 +/- 16 vs 120 +/- 19), whereas [Sar1, Thr8]-ANG II and losartan block Na+ excretion (193 +/- 16 vs 77 +/- 15 and 100 +/- 12, respectively) induced by ANG II. Similar effects induced by ANG II on K+ excretion were observed with [Sar1, Ala8]-ANG II, [Sar1, Thr8]- ANG II, and losartan pretreatment (133 +/- 18 vs 108 +/- 11, 80 +/- 12, and 82 +/- 15, respectively). The same doses as above of [Sar1, Ala8]-ANG II (8 rats), [Sar1, Thr8]-ANG II (8 rats), and losartan (9 rats) blocked the increase in the arterial blood pressure induced by 12 ng of ANG II (12 rats) (32 +/- 4 vs 4 +/- 2, 3.5 +/- 1, and 2 +/- 1, respectively. The results indicate that the AT1 receptor subtype participates in the increases of diuresis, natriuresis, kaliuresis and arterial blood pressure induced by the administration of ANG II into the MnPO.     

The effect of sequential administration of octreotide alone and octreotide/growth hormone simultaneously on buserelin stimulated ovarian steroid secretion in women with polycystic ovary syndrome

The site of S1-S2 root activation following percutaneous high-voltage electrical (ES) and magnetic stimulation were located by analyzing the variations of the time interval from M to H soleus responses elicited by moving the stimulus point from lumbar to low thoracic levels. ES was effective in activating S1-S2 roots at their origin. However supramaximal motor root stimulation required a dorsoventral montage, the anode being a large, circular surface electrode placed ventrally, midline between the apex of the xiphoid process and the umbilicus. Responses to magnetic stimuli always resulted from the activation of a fraction of the fiber pool, sometimes limited to the low-thresholds afferent component, near its exit from the intervertebral foramina, or even more distally. Normal values for conduction velocity in motor and 1a afferent fibers in the proximal nerve tract are provided.     

Comparison of conventional single echo and multi-echo sequences with a fast spin-echo sequence for quantitative T2 mapping: application to the prostate

The accuracy of water T2 maps generated from a fast spin-echo (FSE) sequence was compared with data obtained by conventional single and multi-echo spin-echo pulse sequences using a commercial gel phantom. Spatially localized stimulated echo acquisition mode (STEAM) proton spectroscopy was also used to confirm the reported water T2 values of the gels contained in the phantom. The FSE sequence was shown to be superior in accuracy to both the single and multi-echo spin echo sequences and comparable to STEAM, producing results that were within 10% of known values. The effectiveness of the FSE sequence was further demonstrated by generating T2 maps of the normal and diseased prostate in clinically acceptable imaging times, resulting in comparable T2 values to those obtained using STEAM. Accurate quantitative T2 maps can be produced with the FSE sequence.     

Topical laryngo-tracheal anesthesia and intraocular pressure in anesthesia for ophthalmic surgery

OBJECTIVE: The reflex response to orotracheal intubation provokes an increase of arterial pressure accompanied by an increase of chorioides volume and a consequent ocular hypertone. There are several methods to reduce the reflex response due to intubation. One of the most effective is topical anaesthesia of larynx and trachea. Experiments were directed to evaluate the efficacy of topical anaesthesia to reduce the intraocular hypertone due to orotracheal intubation. DESIGN: A prospective randomized mask study was conduct on patients undergoing ophthalmologic (anterior segment) surgery at the Eye Clinic of Florence University. METHODS: Intraocular pressure was measured by a Goldman tonometer at four times: T0 = basal, T1 = 2' minutes after induction of general anaesthesia, T2 = 2' minutes after laryngoscopy, T3 = 2' minutes after orotracheal intubation. At the same moments, systolic blood pressure, heart rate, rate pressure pro duct were measured. Patients were randomly divided in two groups: Group L (n = 10) in which was evaluated the efficacy of laryngotracheal topical spray of lidocaine 4% (2 ml) and Group F (n = 10) in which saline was used instead of anesthetic. The filling of the LTA kit (Abbott) was made by a person not involved in the experiments. DATA ANALYSIS: Student's t test for unpaired data. RESULTS: Topical anaesthesia reduces the increase of intraocular pressure, hypertension and rate pressure product due to intubation. The intraocular pressure reduces to 13% less than basal value in Group L and increase to 50% more than basal value in Group F. CONCLUSION: The topical anaesthesia of larynx and trachea is effective to reduce the intraocular hypertension due to the reflex response evoked by orotracheal intubation.