Nonlinear dielectric features of highly polar glass formers: Derivatives of propylene carbonate.

We have measured the nonlinear dielectric behavior of several highly polar propylene carbonate (PC) derivatives in the vicinity of their glass transition temperatures. Focus is on the effects of a large static electric field on the frequency dependent permittivity and on the cubic susceptibility measured using sinusoidal fields of high amplitude. The case of vinyl-PC shows dielectric saturation as well as an electro-rheological effect, i.e., a field induced increase of dielectric relaxation times, whose magnitude changes linearly with the apparent activation energy. The extent of this shift of the loss profile caused by the field correlates strongly with the peak magnitude of the cubic susceptibility, |χ3|, underlining the notion of a link between the |χ3| "hump" and this electro-rheological behavior. Further support for this picture emerges from the observation that the most polar of these liquids, (S)-(-)-methoxy-PC with εs ≈ 250, lacks both the electro-rheological effect in ε″(ω) and the "hump" typically observed in |χ3(ω)|. The absence of any sensitivity of the dynamics to an electric field is contrary to the expectation that the electro-rheological effect correlates with the field induced entropy change, which is extraordinarily high for this liquid. The results suggest that the dependence of the relaxation time on the electric field is not directly linked to the entropy change.

Modifying hydrogen-bonded structures by physical vapor deposition: 4-methyl-3-heptanol.

We prepared films of 4-methyl-3-heptanol by vapor depositing onto substrates held at temperatures between Tdep = 0.6Tg and Tg, where Tg is the glass transition temperature. Using deposition rates between 0.9 and 6.0 nm/s, we prepared films about 5 µm thick and measured the dielectric properties via an interdigitated electrode cell onto which films were deposited. Samples prepared at Tdep = Tg display the dielectric behavior of the ordinary supercooled liquid. Films deposited at lower deposition temperatures show a high dielectric loss upon heating toward Tg, which decreases by a factor of about 12 by annealing at Tg = 162 K. This change is consistent with either a drop of the Kirkwood correlation factor, gk, by a factor of about 10, or an increase in the dielectric relaxation times, both being indicative of changes toward ring-like hydrogen-bonded structure characteristic of the ordinary liquid. We rationalize the high dielectric relaxation amplitude in the vapor deposited glass by suggesting that depositions at low temperature provide insufficient time for molecules to form ring-like supramolecular structures for which dipole moments cancel. Surprisingly, above Tg of the ordinary liquid, these vapor deposited films fail to completely recover the dielectric properties of the liquid obtained by supercooling. Instead, the dielectric relaxation remains slower and its amplitude much higher than that of the equilibrium liquid state, indicative of a structure that differs from the equilibrium liquid up to at least Tg + 40 K.

Dynamics of supercooled liquid and plastic crystalline ethanol: Dielectric relaxation and AC nanocalorimetry distinguish structural α- and Debye relaxation processes.

Physical vapor deposition has been used to prepare glasses of ethanol. Upon heating, the glasses transformed into the supercooled liquid phase and then crystallized into the plastic crystal phase. The dynamic glass transition of the supercooled liquid is successfully measured by AC nanocalorimetry, and preliminary results for the plastic crystal are obtained. The frequency dependences of these dynamic glass transitions observed by AC nanocalorimetry are in disagreement with conclusions from previously published dielectric spectra of ethanol. Existing dielectric loss spectra have been carefully re-evaluated considering a Debye peak, which is a typical feature in the dielectric loss spectra of monohydroxy alcohols. The re-evaluated dielectric fits reveal a prominent dielectric Debye peak, a smaller and asymmetrically broadened peak, which is identified as the signature of the structural α-relaxation and a Johari-Goldstein secondary relaxation process. This new assignment of the dielectric processes is supported by the observation that the AC nanocalorimetry dynamic glass transition temperature, Tα, coincides with the dielectric structural α-relaxation process rather than the Debye process. The combined results from dielectric spectroscopy and AC nanocalorimetry on the plastic crystal of ethanol suggest the occurrence of a Debye process also in the plastic crystal phase.

Evaluation of mean conversion coefficients from air-kerma to H *(10) using secondary and transmitted x-ray spectra in the diagnostic radiology energy range.

Ambient dose equivalent H *(10) is an operational quantity recommended by the IAEA to establish dose constraints in area monitoring for external radiation. The direct measurement of H *(10) is not common due to the complexity in the calibration procedures of radiation monitors involving the use of expanded and aligned radiation fields. Therefore, conversion coefficients are used to assess H *(10) from the physical quantity air-kerma. Conversion coefficients published by international commissions, ICRU and ICRP, present a correlation with the radiation beam quality. However, Brazilian regulation establishes 1.14 Sv Gy-1 as unique conversion coefficient to convert air-kerma into H *(10), disregarding its beam quality dependence. The present study computed mean conversion coefficients from secondary and transmitted x-ray beams in order to improve the current assessment of H *(10). The weighting of conversion coefficients corresponding to monoenergetic beams with the spectrum energy distribution in terms of air-kerma was used to compute the mean conversion coefficients. In order to represent dedicated chest radiographic facilities, an anthropomorphic phantom was used as scatter object of the primary beam. Secondary x-ray spectra were measured in the diagnostic energy range at scattering angles of 30°, 60°, 90° 120° and 150° degrees. Barite mortar plates were used as attenuator of the secondary beam to produce the corresponding transmitted x-ray spectra. Results show that the mean conversion coefficients are about 43% higher than the recommended value accepted by Brazilian regulation. For secondary radiation measured at 100 kV the mean coefficient should be 1.46 Sv Gy-1, which represent the higher value in the mean coefficient set corresponding to secondary beams. Moreover, for transmitted x-ray beams at 100 kV, the recommended mean conversion coefficient is 1.65 Sv Gy-1 for all barite mortar plate thickness and all scattering angles. An example of application shows the discrepancy in the evaluation of secondary shielding barriers in a controlled area when the shielding goals is evaluated. The conclusion based on these results is that a unique coefficient may not be adequate for deriving the H *(10).

Oclacitinib (APOQUEL(®)) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy.

Janus kinase (JAK) enzymes are involved in cell signaling pathways activated by various cytokines dysregulated in allergy. The objective of this study was to determine whether the novel JAK inhibitor oclacitinib could reduce the activity of cytokines implicated in canine allergic skin disease. Using isolated enzyme systems and in vitro human or canine cell models, potency and selectivity of oclacitinib was determined against JAK family members and cytokines that trigger JAK activation in cells. Oclacitinib inhibited JAK family members by 50% at concentrations (IC50 's) ranging from 10 to 99 nm and did not inhibit a panel of 38 non-JAK kinases (IC50 's > 1000 nM). Oclacitinib was most potent at inhibiting JAK1 (IC50 = 10 nM). Oclacitinib also inhibited the function of JAK1-dependent cytokines involved in allergy and inflammation (IL-2, IL-4, IL-6, and IL-13) as well as pruritus (IL-31) at IC50 's ranging from 36 to 249 nM. Oclacitinib had minimal effects on cytokines that did not activate the JAK1 enzyme in cells (erythropoietin, granulocyte/macrophage colony-stimulating factor, IL-12, IL-23; IC50 's > 1000 nM). These results demonstrate that oclacitinib is a targeted therapy that selectively inhibits JAK1-dependent cytokines involved in allergy, inflammation, and pruritus and suggests these are the mechanisms by which oclacitinib effectively controls clinical signs associated with allergic skin disease in dogs.

Graft-versus-host disease after double-unit cord blood transplantation has unique features and an association with engrafting unit-to-recipient HLA match.

Manifestations of and risk factors for graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age, 37 years) who underwent transplantation for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor/mycophenolate mofetil immunosuppression. Incidence of day 180 grades II to IV and III to IV acute GVHD (aGVHD) were 53% (95% confidence interval, 44 to 62) and 23% (95% confidence interval, 15 to 31), respectively, with a median onset of 40 days (range, 14 to 169). Eighty percent of patients with grades II to IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD, with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome. Late GVHD in the form of classic chronic GVHD was uncommon. Notably, grades III to IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A, -B, -DRB1 allele match was >4/6 to the recipient (hazard ratio, 0.385; P = .031), whereas engrafting unit infused nucleated cell dose and unit-to-unit HLA match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, and had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor-recipient (but not unit-unit) HLA match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.

First Report of Dolabra nepheliae Associated with Corky Bark Disease of Rambutan and Pulasan in Honduras.

In the last decade, rambutan (Nephelium lappaceum L., Sapindaceae) and pulasan (N. mutabile Blume) have been cultivated in Honduras to produce exotic fruits for export to North America (2). Recently, a disease was observed that produces dark brown to black fissured cankers from 1 to 3 cm long and 1 to 4 cm wide. The infected bark tissue becomes swollen with the middle region 3 to 8 mm thick. Symptoms appear when the trees are approximately 3 years old. As the trees mature, the cankers increase in size and weaken the branches, often resulting in breakage with the weight of the fruit causing substantial plant damage and fruit loss. In August 2010, fissured branch samples of rambutan and pulasan were collected from 6- to 8-year-old trees from the Humid Tropical Demonstrative Agroforestry Center in Honduras, Atlantida, La Masica (15°33'47.4″N, 87°05'2.5″W, elevation 106 m). A fungus associated with the cankers was identified as Dolabra nepheliae. It produces black, stipitate, elongate ascomata, 312 to 482 × 250 to 281 µm with broadly cylindric, bitunicate asci, 120 to 138 × 11.2 to 15.0 µm, and filiform, hyaline ascospores, 128 to 135 × 2.8 to 3.2 µm. Fungi from rambutan and pulasan were isolated on cornmeal agar plus 0.5% dextrose and antibiotics. On potato dextrose agar, the ascospores produced slow-growing colonies, 5 mm per week. In culture, isolates from both hosts produced pycnidia with elongated, slightly to strongly curved or S-shaped, hyaline conidia, 22.8 to 46.4 × 2.8 to 3.7 µm. This fungus was first reported on rambutan and pulasan from Malaysia (1,4), and later reported on rambutan and litchi in Hawaii and Puerto Rico (3). To our knowledge, this is the first report of D. nepheliae on pulasan and rambutan from Honduras. Specimens have been deposited at the U.S. National Fungus Collections (BPI 882442 on N. lappaceum and BPI 882443 on N. mutabile). Cultures were deposited at the Centraalbureau voor Schimmelcultures (CBS) as CBS 131490 on N. lappaceum and CBS 131491 on N. mutabile. Sequences of the internal transcribed spacer (ITS) region including ITS1, 5.8S, and ITS2 intergenic spacers were deposited in GenBank (Accession No. JQ004281 on N. lappaceum and Accession No. JQ004280 on N. mutabile). A BLAST search and pairwise comparison using the GenBank web server were used to compare ITS sequence data and recovered the following results: (i) CBS 131490 on N. lappaceum is 99% (538 of 544) identical to D. nepheliae CBS 123297 on Litchi chinensis from Puerto Rico; and (ii) CBS 131491 on N. mutabile is 99% (527 of 533) identical to the same strain of D. nepheliae. On the basis of the ITS sequence data, the isolates from Honduras were confirmed as the same species, D. nepheliae from Puerto Rico. Efforts to develop resistant germplasm and management strategies to control this disease have been initiated. References: (1) C. Booth and W. P. Ting. Trans. Brit. Mycol. Soc. 47:235, 1964. (2) T. Ramírez et al. Manual Para el Cultivo de Rambutan en Honduras. Fundación Hondureña de Investigación Agrícola. La Lima, Cortes, Honduras, 2003. (3) A. Y. Rossman et al. Plant Dis. 91:1685, 2007. (4) H. Zalasky et al. Can. J. Bot. 49:559, 1971.

APPLICATION OF THE MONTE CARLO METHOD FOR THE EVALUATION OF SCATTERED RADIATION DOSE DUE TO THE USE OF HANDHELD X-RAY IN DENTISTRY.

The object of this study was to evaluate the dose of scattered radiation in the organs of the operator and assistant located in different positions within a dental room when acquiring intraoral images with a portable handheld X-ray device, using Monte Carlo simulations for recommended and traditional techniques. A typical dental installation was modeled, where the operator and assistant were placed. The beam is represented by 60-kV spectrum. Ten scenarios were simulated, representing different positions and use of the lead apron. The results of the simulations were carried out with typical parameters of the annual workload, showing significant increases in dose in the organs of the operator due to the angulation. The minimum dose in the organs of the assistant occurred when he was located 2-m away and 45° from the direction of the beam. The dose received by the operator is significantly reduced with the use apron.

Monte Carlo simulations and phantom validation of low-dose radiotherapy to the lungs using an interventional radiology C-arm fluoroscope.

PURPOSE: To use MC simulations and phantom measurements to investigate the dosimetry of a kilovoltage x-ray beam from an IR fluoroscope to deliver low-dose (0.3-1.0 Gy) radiotherapy to the lungs. MATERIALS AND METHODS: PENELOPE was used to model a 125 kV, 5.94 mm Al HVL x-ray beam produced by a fluoroscope. The model was validated through depth-dose, in-plane/cross-plane profiles and absorbed dose at 2.5-, 5.1-, 10.2- and 15.2-cm depths against the measured beam in an acrylic phantom. CT images of an anthropomorphic phantom thorax/lungs were used to simulate 0.5 Gy dose distributions for PA, AP/PA, 3-field and 4-field treatments. DVHs were generated to assess the dose to the lungs and nearby organs. Gafchromic film was used to measure doses in the phantom exposed to PA and 4-field treatments, and compared to the MC simulations. RESULTS: Depth-dose and profile results were within 3.2% and 7.8% of the MC data uncertainty, respectively, while dose gamma analysis ranged from 0.7 to 1.0. Mean dose to the lungs were 1.1-, 0.8-, 0.9-, and 0.8- Gy for the PA, AP/PA, 3-field, and 4-field after isodose normalization to cover âˆ¼ 95% of each lung volume. Skin dose toxicity was highest for the PA and lowest for the 4-field, and both arrangements successfully delivered the treatment on the phantom. However, the dose distribution for the PA was highly non-uniform and produced skin doses up to 4 Gy. The dose distribution for the 4-field produced a uniform 0.6 Gy dose throughout the lungs, with a maximum dose of 0.73 Gy. The average percent difference between experimental and Monte Carlo values were -0.1% (range -3% to +4%) for the PA treatment and 0.3% (range -10.3% to +15.2%) for the 4-field treatment. CONCLUSION: A 125 kV x-ray beam from an IR fluoroscope delivered through two or more fields can deliver an effective low-dose radiotherapy treatment to the lungs. The 4-field arrangement not only provides an effective treatment, but also significant dose sparing to healthy organs, including skin, compared to the PA treatment. Use of fluoroscopy appears to be a viable alternative to megavoltage radiation therapy equipment for delivering low-dose radiotherapy to the lungs.

Low-dose radiotherapy to the lungs using an interventional radiology C-arm fluoroscope: Monte Carlo treatment planning and dose measurements in a postmortem subject.

Objective.The goal of this study was to use Monte Carlo (MC) simulations and measurements to investigate the dosimetric suitability of an interventional radiology (IR) c-arm fluoroscope to deliver low-dose radiotherapy to the lungs.Approach.A previously-validated MC model of an IR fluoroscope was used to calculate the dose distributions in a COVID-19-infected patient, 20 non-infected patients of varying sizes, and a postmortem subject. Dose distributions for PA, AP/PA, 3-field and 4-field treatments irradiating 95% of the lungs to a 0.5 Gy dose were calculated. An algorithm was created to calculate skin entrance dose as a function of patient thickness for treatment planning purposes. Treatments were experimentally validated in a postmortem subject by using implanted dosimeters to capture organ doses.Main results.Mean doses to the left/right lungs for the COVID-19 CT data were 1.2/1.3 Gy, 0.8/0.9 Gy, 0.8/0.8 Gy and 0.6/0.6 Gy for the PA, AP/PA, 3-field, and 4-field configurations, respectively. Skin dose toxicity was the highest probability for the PA and lowest for the 4-field configuration. Dose to the heart slightly exceeded the ICRP tolerance; all other organ doses were below published tolerances. The AP/PA configuration provided the best fit for entrance skin dose as a function of patient thickness (R2 = 0.8). The average dose difference between simulation and measurement in the postmortem subject was 5%.Significance.An IR fluoroscope should be capable of delivering low-dose radiotherapy to the lungs with tolerable collateral dose to nearby organs.

Trace metal content in mussels, Perna viridis L., obtained from selected seafood markets in a Metropolitan City.

Mussels, Perna viridis L., obtained from three selected seafood markets in Metro Manila, were tested for metal content including cadmium, copper, lead, and zinc through atomic absorption spectrophotometry. Water samples from Bacoor Bay, Cavite, which supplies mussels to the market, were likewise subjected to similar metal analyses. Of the metals analyzed in the soft tissues of mussels, only copper and lead with highest obtained values of 10.4 mg/kg and 2.3 mg/kg, respectively exceeded the PEMSEA guideline for safe human consumption. Water samples collected from the harvest sites in Bacoor Bay showed high concentrations of cadmium (0.023 mg/L) and lead (0.25 mg/L) that exceeded the standards of DENR, ASEAN, and US EPA. Zinc, though detected in relatively high concentrations in both water (0.03 mg/L) and soft tissues (12.16-14.43 mg/kg) of mussels remained below the criteria set by the above-mentioned agencies. Overall, the present study indicates that mussels being sold in selected Metro Manila seafood markets were contaminated with metals, notably Cu and Pb, at concentrations that are unsafe for human consumption and thus, represents a health risk.

Performance of Standardized Relative CBV for Quantifying Regional Histologic Tumor Burden in Recurrent High-Grade Glioma: Comparison against Normalized Relative CBV Using Image-Localized Stereotactic Biopsies.

BACKGROUND AND PURPOSE: Perfusion MR imaging measures of relative CBV can distinguish recurrent tumor from posttreatment radiation effects in high-grade gliomas. Currently, relative CBV measurement requires normalization based on user-defined reference tissues. A recently proposed method of relative CBV standardization eliminates the need for user input. This study compares the predictive performance of relative CBV standardization against relative CBV normalization for quantifying recurrent tumor burden in high-grade gliomas relative to posttreatment radiation effects. MATERIALS AND METHODS: We recruited 38 previously treated patients with high-grade gliomas (World Health Organization grades III or IV) undergoing surgical re-resection for new contrast-enhancing lesions concerning for recurrent tumor versus posttreatment radiation effects. We recovered 112 image-localized biopsies and quantified the percentage of histologic tumor content versus posttreatment radiation effects for each sample. We measured spatially matched normalized and standardized relative CBV metrics (mean, median) and fractional tumor burden for each biopsy. We compared relative CBV performance to predict tumor content, including the Pearson correlation (r), against histologic tumor content (0%-100%) and the receiver operating characteristic area under the curve for predicting high-versus-low tumor content using binary histologic cutoffs (≥50%; ≥80% tumor). RESULTS: Across relative CBV metrics, fractional tumor burden showed the highest correlations with tumor content (0%-100%) for normalized (r = 0.63, P < .001) and standardized (r = 0.66, P < .001) values. With binary cutoffs (ie, ≥50%; ≥80% tumor), predictive accuracies were similar for both standardized and normalized metrics and across relative CBV metrics. Median relative CBV achieved the highest area under the curve (normalized = 0.87, standardized = 0.86) for predicting ≥50% tumor, while fractional tumor burden achieved the highest area under the curve (normalized = 0.77, standardized = 0.80) for predicting ≥80% tumor. CONCLUSIONS: Standardization of relative CBV achieves similar performance compared with normalized relative CBV and offers an important step toward workflow optimization and consensus methodology.

Case report on the clinical results of a combined cellular therapy for chronic spinal cord injured patients.

OBJECTIVES: With the intention to ameliorate the clinical condition of patients with chronic spinal cord injury (SCI), a program that combines three cell therapies and an appropriate neurorehabilitation program were used to recreate and enhance the natural conditions of SCI repair. METHODS: Vascularization recovery is approached by selective artery infusion of BMMNCs (bone marrow mononuclear cells) to the disrupted area. Eighteen days later, with the aim to restore the specific inflammatory activity, an i.v. infusion of spinal cord specific ETCs (effector T cells) is carried out. With the intention of supplying cellular components for the process of repair, an infusion of autologous neural stem cells (NSCs) through selective feeding artery infusion is carried out, followed by an appropriate neurorehabilitation program. RESULTS: A total of eight ASIA (American Spinal Injury Association) A patients (five with jeopardized brachial plexus and three without) received the treatment. No severe adverse events was observed in any of the receptor patients: five patients evolved from ASIA A to ASIA D and regained the ability to stand up and, with varying effectiveness, to walk; two patients remained in the same condition, but exhibited motor and sensitive improvements; and one patient could not be evaluated. CONCLUSIONS: These reports suggest that the biological characteristics of acute SCI may be recreated in a comprehensive, safe and effective manner.

The brain-derived neurotrophic factor VAL68MET polymorphism modulates how developmental ethanol exposure impacts the hippocampus.

Prenatal exposure to alcohol causes a wide range of deficits known as fetal alcohol spectrum disorders (FASDs). Many factors determine vulnerability to developmental alcohol exposure including timing and pattern of exposure, nutrition and genetics. Here, we characterized how a prevalent single nucleotide polymorphism in the human brain-derived neurotrophic factor (BDNF) gene (val66met) modulates FASDs severity. This polymorphism disrupts BDNF's intracellular trafficking and activity-dependent secretion, and has been linked to increased incidence of neuropsychiatric disorders such as depression and anxiety. We hypothesized that developmental ethanol (EtOH) exposure more severely affects mice carrying this polymorphism. We used transgenic mice homozygous for either valine (BDNFval/val ) or methionine (BDNFmet/met ) in residue 68, equivalent to residue 66 in humans. To model EtOH exposure during the second and third trimesters of human pregnancy, we exposed mice to EtOH in vapor chambers during gestational days 12 to 19 and postnatal days 2 to 9. We found that EtOH exposure reduces cell layer volume in the dentate gyrus and the CA1 hippocampal regions of BDNFmet/met but not BDNFval/val mice during the juvenile period (postnatal day 15). During adulthood, EtOH exposure reduced anxiety-like behavior and disrupted trace fear conditioning in BDNFmet/met mice, with most effects observed in males. EtOH exposure reduced adult neurogenesis only in the ventral hippocampus of BDNFval/val male mice. These studies show that the BDNF val66met polymorphism modulates, in a complex manner, the effects of developmental EtOH exposure, and identify a novel genetic risk factor that may regulate FASDs severity in humans.

Report of initial experience in small bowel transplantation at São José do Rio Preto Medical School Hospital.

Intestinal failure is the patient's inability to maintain hydroelectric and nutritional support by the digestive route, arising from massive enterectomy or diseases in which the bowel is incapable of adequately absorbing fluids and nutrients. Patients with intestinal failure associated with short bowel syndrome (SBS) and with other functional diseases with malabsorption or with total parenteral nutrition-related complications (recurrent sepsis and thrombosis of one or more deep venous accesses) are candidates for small bowel transplantation (SBT), which can be an isolated small bowel, a combined liver and small bowel, or a multivisceral graft. At our institution, three isolated SBTs were performed as our initial experience with this transplant.

Modulation of CCK-8-evoked intracellular Ca2+ waves by hydrogen peroxide in mouse pancreatic acinar cells.

In the present study we have employed single cell imaging analysis to monitor the propagation of cholecystokinin-evoked Ca(2+) waves in mouse pancreatic acinar cells. Stimulation of cells with 1 nM CCK-8 led to an initial Ca(2+) release at the luminal cell pole and subsequent spreading of the Ca(2+) signal towards the basolateral membrane in the form of a Ca(2+) wave. Inhibition of sarcoendoplasmic reticulum Ca(2+)-ATPase (SERCA) activity by 1 microM thapsigargin, preincubation in the presence of 100 microM H(2)O(2) or inhibition of PKC with either 5 microM Ro31-8220 or 3 microM GF-109203-X all led to a faster propagation of CCK-8-induced Ca(2+) signals. The propagation of CCK-8-evoked Ca(2+) signals was slowed down by activation of PKC with 1 microM PMA, and preincubation of cells in the presence of H(2)O(2) counteracted the effect of PKC inhibition. The protonophore FCCP (100 nM) and the inhibitor of the mitochondrial Ca(2+)-uniporter Ru360 (10 microM) led to an increase in the propagation rate of CCK-8-evoked Ca(2+) waves. Finally, depolymerisation of actin cytoskeleton with cytochalasin D (10 microM) led to a faster propagation of CCK-8-evoked Ca(2+) signals. Stabilization of actin cytoskeleton with jasplakinolide (10 microM) did not induce significant changes on CCK-8-evoked Ca(2+) waves. Preincubation of cells in the presence of H(2)O(2) counteracted the effect of cytochalasin D on CCK-8-evoked Ca(2+) wave propagation. Our results suggest that spreading of cytosolic Ca(2+) waves evoked by CCK-8 can be modulated by low levels of oxidants acting on multiple Ca(2+)-handling mechanisms.

Continuous renal replacement therapy in neonates and young infants during extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a therapy that ensures adequate tissue oxygen delivery in patients suffering cardiac and/or respiratory failure that are unresponsive to conventional therapy. During ECMO, it is common to see a decrease in urine output that may be associated with acute renal failure. In this context, continuous renal replacement therapy (CRRT) should be considered. Our aim is to evaluate a pioneer experience in Latin America, related to the use of CRRT in a group of neonatal-pediatric patients during ECMO. We conducted a retrospective review of patients treated with ECMO at our institution between May 2003 and May 2005. Twelve infants were treated with ECMO, six of them also underwent CRRT. The main reasons for CRRT initiation were fluid overload and progressive azotemia. Observed complications were clots in the filter and excessive ultrafiltration. CRRT was successful in fluid management and solute clearance in all patients. Discharge survival rate was 83%, all of them with normal renal function. Concurrent CRRT with ECMO is technically feasible and efficacious in the management of fluid overload and solute clearance. We report the first experience with these therapies in a Latin American neonatal-pediatric ECMO program associated with the Extracorporeal Life Support Organization.

Outbreak of Notozothecium bethae (Monogenea: Dactylogyridae) in Myleus schomburgkii (Actinopterygii: Characiformes) cultured in the Peruvian Amazon.

The presence of Notozothecium bethae was investigated in 76 black band myleus (Myleus schomburgkii [Actinopterygii: Charasiformes]) born and kept in captivity in two semi-intensive breeding cages in the northern region of Peru. Among the 76 cultivated specimens of M. schomburgkii examined in the present study, 100 % had monogenean on the gill and the parasites were identified as Notozothecium bethae. During the survey no bacteria was isolated, and no protozoan or other metazoan parasites were found. The prevalence of N. bethae remained constant throughout the present study. Mean intensity of N. bethae in the months of April and May was exceptionally high in both facilities. The massive infection of N. bethae on the gills of M. schomburgkii was associated with mortality. This is the first report of N. bethae in M. schomburgkii born in captivity and cultured in the Amazon region. The mortality due the presence of this parasite emphasise the need for disease control strategies of cultured M. schomburgkii.

Characterization of the apoptosis-associated tyrosine kinase (AATYK) expressed in the CNS.

We isolated three related cDNA clones from a mouse cerebellar library; the type I cDNA was identical to the gene encoding the apoptosis-associated tyrosine kinase (AATYK), whose expression in myeloid precursor cells is increased during growth arrest or apoptosis. Low levels of AATYK mRNA expression were seen in adult mouse brains but not in embryos. In situ hybridization confirmed the widespread expression of AATYK mRNA in neurons throughout the adult brain. AATYK possessed tyrosine kinase activity and was autophosphorylated when expressed in 293 cells. AATYK mRNA expression was rapidly induced in cultured cerebellar granule cells during apoptosis induced by a low concentration of KCl (5 mM). Levels of endogenous AATYK protein were increased only slightly, but they were accompanied by an increase in molecular weight during apoptosis. Results of the tyrosine phosphatase treatments indicated that the increase in molecular weight was partly caused by tyrosine phosphorylation. The number of apoptotic granule cells overexpressing wild-type AATYK protein was significantly greater than the number of apoptotic granule cells overexpressing a mutant AATYK that lacked tyrosine kinase activity in low concentrations of KCl. These findings suggest that through its tyrosine kinase activity, AATYK is involved in the apoptosis of mature neurons.

CT-angiography for the detection of a lower gastrointestinal bleeding source.

The evaluation of lower gastrointestinal bleeding (LGIB) often involves the collaborative efforts of the gastroenterologist, radiologist, and surgeon. Efforts to localize the acute LGIB have traditionally involved colonoscopy, technetium-labeled red blood cell (RBC) scintigraphy, angiography, or a combination of these modalities. The sensitivity of each method of diagnosis is limited, with the most common cause of a negative study the spontaneous cessation of hemorrhage. Other technical factors include vasospasm, lack of adequate contrast volume or exposure time, a venous bleeding source, and a large surface bleeding area. We report the use of multidetector computed tomography (MDCT), or CT-angiography (CT-A), in the initial evaluation of LGIB, and speculate on the incorporation of this technique into a diagnostic algorithm to treat LGIB. MDCT may offer a very sensitive means to evaluate the source of acute LGIB, while avoiding some of the morbidity and intense resource use of contrast angiography, and may provide unique morphologic information regarding the type of pathology. Screening with the more rapid and available MDCT, followed by either directed therapeutic angiography or surgical management, may represent a reasonable algorithm for the early evaluation and management of acute LGIB in which an active bleeding source is strongly suspected.