Inhibition of Growth of Toxoplasma Gondii in Cultured Fibroblasts by Human Recombinant Gamma Interferon.

The growth of Toxoplasma gondii in cultured human fibroblasts was inhibited by recombinant human gamma interferon at concentrations of 8 to 16 U/ml. The interferon was titrated by observing a total inhibition of parasite plaque formation 7 days after infection. Inhibition of the growth of T. gondii in the early days after infection was measured by marked reductions in the incorporation of radioactive uracil, a precursor that can only be used by the parasites. This assay showed that when cells were pretreated with gamma interferon for 1 day and then infected, inhibition of T. gondii growth could be readily detected 1 or 2 days after infection. When the pretreatment was omitted and parasites and gamma interferon were added at the same time, no inhibition of parasite growth could be detected 1 day later, although it was apparent after 2 days. Cultures from which the gamma interferon had been removed by washing after a 1-day treatment showed inhibition of T. gondii growth. Gamma interferon had no effect on the viability of extracellular parasites, but it did inhibit the synthesis of host cell RNA and protein by ca. 50% 3 days after treatment. This degree of inhibition is unlikely, of itself, to compromise the growth of T. gondii. Recombinant alpha and beta interferons had no effect on the growth of T. gondii

Gallbladder Ejection Fraction is Unrelated to Gallbladder Pathology in Children and Adolescents

Objectives: Biliary dyskinesia is a common diagnosis that frequently results in cholecystectomy. In adults, most clinicians use a cut off value for the gallbladder ejection fraction (GBEF) of <35% to define the disease. This disorder is not well characterized in children. Our aim was to determine the relation between GBEF and gallbladder pathology using a large statewide medical record repository. Methods: We obtained records from all patients of 21 years and younger who underwent hepatic iminodiacetic acid (HIDA) testing within the Indiana Network for Patient Care from 2004 to 2013. GBEF results were obtained from radiology reports using data mining techniques. Age, sex, race, and insurance status were obtained for each patient. Any gallbladder pathology obtained subsequent to an HIDA scan was also obtained and parsed for mention of cholecystitis, cholelithiasis, or cholesterolosis. We performed mixed effects logistic regression analysis to determine the influence of age, sex, race, insurance status, pathologist, and GBEF on the presence of these histologic findings. Results: Two thousand eight hundred forty-one HIDA scans on 2558 patients were found. Of these, 310 patients had a full-text gallbladder pathology report paired with the HIDA scan. GBEF did not correlate with the presence of gallbladder pathology (cholecystitis, cholelithiasis, or cholesterolosis) when controlling for age, sex, race, insurance status, and pathologist using a mixed effects model. Conclusions: Hypokinetic gallbladders are no more likely to have gallbladder pathology than normal or hyperkinetic gallbladders in the setting of a patient with both a HIDA scan and a cholecystectomy. Care should be used when interpreting the results of HIDA scans in children and adolescents

Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis

Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasites &lt;i&gt;Trypanosoma brucei rhodesiense&lt;/i&gt; or &lt;i&gt;Trypanosoma brucei gambiense&lt;/i&gt;, and is a major cause of systemic and neurological disability throughout sub-Saharan Africa. Following early-stage disease, the trypanosomes cross the blood-brain barrier to invade the central nervous system leading to the encephalitic, or late stage, infection. Treatment of human African trypanosomiasis currently relies on a limited number of highly toxic drugs, but untreated, is invariably fatal. Melarsoprol, a trivalent arsenical, is the only drug that can be used to cure both forms of the infection once the central nervous system has become involved, but unfortunately, this drug induces an extremely severe post-treatment reactive encephalopathy (PTRE) in up to 10% of treated patients, half of whom die from this complication. Since it is unlikely that any new and less toxic drug will be developed for treatment of human African trypanosomiasis in the near future, increasing attention is now being focussed on the potential use of existing compounds, either alone or in combination chemotherapy, for improved efficacy and safety. The kynurenine pathway is the major pathway in the metabolism of tryptophan. A number of the catabolites produced along this pathway show neurotoxic or neuroprotective activities, and their role in the generation of central nervous system inflammation is well documented. In the current study, Ro-61-8048, a high affinity kynurenine-3-monooxygenase inhibitor, was used to determine the effect of manipulating the kynurenine pathway in a highly reproducible mouse model of human African trypanosomiasis. It was found that Ro-61-8048 treatment had no significant effect (P = 0.4445) on the severity of the neuroinflammatory pathology in mice during the early central nervous system stage of the disease when only a low level of inflammation was present. However, a significant (P = 0.0284) reduction in the severity of the neuroinflammatory response was detected when the inhibitor was administered in animals exhibiting the more severe, late central nervous system stage, of the infection. &lt;i&gt;In vitro&lt;/i&gt; assays showed that Ro-61-8048 had no direct effect on trypanosome proliferation suggesting that the anti-inflammatory action is due to a direct effect of the inhibitor on the host cells and not a secondary response to parasite destruction. These findings demonstrate that kynurenine pathway catabolites are involved in the generation of the more severe inflammatory reaction associated with the late central nervous system stages of the disease and suggest that Ro-61-8048 or a similar drug may prove to be beneficial in preventing or ameliorating the PTRE when administered as an adjunct to conventional trypanocidal chemotherap

Measurement of Tool-Workpiece Interface Temperature Distribution in Friction Stir Welding

The objective of this work is to develop an improved temperature measurement system for friction stir welding (FSW). FSW is a solid-state joining process enabling welds with excellent metallurgical and mechanical properties, as well as significant energy consumption and cost savings compared to traditional fusion welding processes. The measurement of temperatures during FSW is needed for process monitoring, heat transfer model verification and process control, but current methods have limitations due to their restricted spatial and temporal resolution. Previous work showed that temperatures at the tool shoulder-workpiece interface can be measured and utilized for closed-loop control of temperature. Adding an additional thermocouple at the tool pin-workpiece interface and performing a calibration of the measurement to gain better insight into the temperature distribution in the weld zone improved the method. Both thermocouples were placed in through holes right at the interface of tool so that the sheaths are in direct contact with the workpiece material. This measurement strategy reveals dynamic temperature variations at the shoulder and the pin within a single rotation of the tool in realtime. It was found that the highest temperatures are at the shoulder interface between the advancing side and the trailing edge of the tool, closer to the advancing side. The temperature distribution was mostly affected by travel speed and the temperature difference within one tool rotation was found to be between 10 C and 50 C, depending on the process parameters. The dynamic temperature measurements obtained with the current system are of unmatched resolution, fast, and reliable and are likely to be of interest for both fundamental studies and process control of FSW

Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

IMECE2008-69051 EXPERIMENTAL STUDY OF ADIABATIC WATER LIQUID-VAPOR TWO-PHASE PRESSURE DROP ACROSS AN ARRAY OF STAGGERED MICRO-PIN-FINS

ABSTRACT This study concerns pressure drop of adiabatic water liquid-vapor two-phase flow across an array of 1950 staggered square micro-pin-fins having a 200×200 micron cross-section by a 670 micron height. The ratios of longitudinal pitch and transverse pitch to pin-fin equivalent diameter are equal to 2. An inline immersion heater upstream of the micro-pin-fin test module was employed to produce liquid-vapor two-phase mixture, which flowed across the micro-pin-fin array. The test module was well insulated to maintain an adiabatic condition. Four maximum mass velocities of 184, 235, 337, and 391 kg/m²s, and a range of vapor qualities for each maximum mass velocity were tested. Measured pressure drop increases drastically with increasing vapor quality. Nine existing twophase pressure drop models and correlations were assessed. The Lockhart-Martinelli correlation for laminar liquid-laminar vapor combination in conjunction with a single-phase friction factor correlation proposed for the present micro-pin-fin array provided the best agreement with the data