Single dose pharmacodynamics of amphotericin B against Aspergillus species in an in vitro pharmacokinetic/pharmacodynamic model

Conventional MIC testing of amphotericin B results in narrow MIC ranges challenging the detection of resistant strains. In order to discern amphotericin B pharmacodynamics, the in vitro activity of amphotericin B was studied against Aspergillus isolates with the same MIC with a new in vitro pharmacokinetic/pharmacodynamic (PK/PD) model that simulates amphotericin B human plasma levels. Clinical isolates of A. fumigatus, A. terreus and A flavus with the same CLSI modal MICs of 1 mg/l were exposed to amphotericin B concentrations following the plasma concentration-time profile after single bolus administration with Cmax 0.6, 1.2, 2.4 and 4.8 mg/L. Fungal growth was monitored up to 72h based on galactomannan production. Complete growth inhibition was observed only against A. fumigatus with amphotericin B Cmax ≥2.4 mg/L. At lower Cmaxs 0.6 and 1.2 mg/L, a significant growth delay of 34h and 52h was observed, respectively (pA flavus>A. terreus in the in vitro PK/PD model possibly reflecting the different concentration- and time-dependent inhibitory/killing activities amphotericin B exerting against these species

Final Project Report: Hydraulic Model Study Wastewater Influent Splitter Chamber Project 88 Southerly Wastewater Treatment Plant Columbus, Ohio

https://deepblue.lib.umich.edu/bitstream/2027.42/154194/1/39015101405192.pd

The Incidence, Management, and Outcome of Penetrating Bladder Injuries in Civilians Resultant from Armed Conflict in Baghdad 2005-2006

The purpose of this paper is to review the diagnosis, treatment, and outcomes of penetrating bladder injuries suffered by civilians in the Iraqi war zone. Materials and Methods. All civilian trauma cases received alive at Al-Yarmouk Teaching Hospital from January 2005 to August 2006 were reviewed for the presence of bladder injury. Results. 533 cases of penetrating abdominal trauma were identified, of which 177 (33%) involved the genitourinary (GU) system and 64 (12%) involved the bladder. Most (70%) were young males, and most (55%) had grade IV injuries. Associated injuries occurred in 63/64 (98%) of patients. 3 patients had missed bladder injuries, and all of these had complications related to their missed injury. Bladder-related complications occurred in 11% of cases, and mortality in 13%, all due to extravesical injuries. Conclusions. Penetrating bladder injury among civilians in Baghdad war zone resulted in 64 cases in 18 months. The initial detection rate is very high (98%), and after primary repair, lasting complications are rare. Morbidities from missed injuries were severe hematuria and vesicorectal fistula. However, (3%) of vesicorectal fistulae healed spontaneously with prolonged bladder drainage. Associated injuries are the rule in penetrating bladder injury patients, and must be diligently investigated and treated

Effect of season on embryo production in Iraqi local black goat

The aim of this study was to investigate the effect of season on embryo production in Iraqi local black goat. 599 female genital system of Iraqi local black goat were collected from AL-Fallujah abattoir, AL-Anbar province during the period from July 2010 to the 1st July 2011. The oocytes were collected via aspiration and slicing. Only good and fair quality oocytes were selected for in vitro maturation. Fresh semen were used from two Bucks of proven fertility for fertilization . TALP , MEM , and TCM-199 culture media were used of in-vitro maturation (IVM) and in-vitro fertilization (IFV). It has been shown that high recovery and maturation rate 87.3% and 45.6% respectively were observed at breeding season as compared with recovery rate 72.5% and maturation rate 35.2% respectively in non-breeding season. There was a significant difference (P˂0.05) in recovery rate and maturation rate between different season. It has been found that fertilization rate was 60.05% in breeding season. While it has 33.9% in non-breeding season. There was a significant difference in fertilization rate (P˂0.05) between breeding and non-breeding season. Blastocyst obtained during breeding season was 56.41% , while it was 43.24% in non-breeding season. There was a significant difference (P˂0.05) between different season. It was concluded that there is an effect of season on oocyte recovery

Inositol pentakisphosphate isomers bind PH domains with varying specificity and inhibit phosphoinositide interactions

<p>Abstract</p> <p>Background</p> <p>PH domains represent one of the most common domains in the human proteome. These domains are recognized as important mediators of protein-phosphoinositide and protein-protein interactions. Phosphoinositides are lipid components of the membrane that function as signaling molecules by targeting proteins to their sites of action. Phosphoinositide based signaling pathways govern a diverse range of important cellular processes including membrane remodeling, differentiation, proliferation and survival. <it>Myo-</it>Inositol phosphates are soluble signaling molecules that are structurally similar to the head groups of phosphoinositides. These molecules have been proposed to function, at least in part, by regulating PH domain-phosphoinositide interactions. Given the structural similarity of inositol phosphates we were interested in examining the specificity of PH domains towards the family of <it>myo-</it>inositol pentakisphosphate isomers.</p> <p>Results</p> <p>In work reported here we demonstrate that the C-terminal PH domain of pleckstrin possesses the specificity required to discriminate between different <it>myo-</it>inositol pentakisphosphate isomers. The structural basis for this specificity was determined using high-resolution crystal structures. Moreover, we show that while the PH domain of Grp1 does not possess this high degree of specificity, the PH domain of protein kinase B does.</p> <p>Conclusions</p> <p>These results demonstrate that some PH domains possess enough specificity to discriminate between myo-inositol pentakisphosphate isomers allowing for these molecules to differentially regulate interactions with phosphoinositides. Furthermore, this work contributes to the growing body of evidence supporting <it>myo</it>-inositol phosphates as regulators of important PH domain-phosphoinositide interactions. Finally, in addition to expanding our knowledge of cellular signaling, these results provide a basis for developing tools to probe biological pathways.</p

Thermally induced magnetization dynamics of optically excited YIG/Cu/Ni81Fe19 trilayers

This is the final version of the article. Available from American Physical Society via the DOI in this record.The response of Y3Fe5O12/Cu/Ni81Fe19 trilayer structures to excitation by a femtosecond laser pulse has been studied in optical pump-probe experiments and compared with the response of Y3Fe5O12 (YIG) and Ni81Fe19 reference samples. The optical pump induces a partial demagnetization of the Ni81Fe19, a large thermal gradient within the YIG, and temperature differences across the interfaces within the sample stack. When a moderate magnetic field is applied close to normal to the sample plane, so as to quasialign the YIG magnetization with the field and cant the Ni81Fe19 magnetization from the plane, ultrafast demagnetization initiates precession of the Ni81Fe19 magnetization. The transient temperature profile within the samples has been modeled using a one-dimensional finite-element computational model of heat conduction, while the magnetization dynamics are well described by a macrospin solution of the Landau-Lifshitz-Gilbert equation. The precessional response of the Ni81Fe19 layers within the trilayers and the Ni81Fe19 reference sample are very similar for pump fluences of up to 1.5 mJ/cm2, beyond which irreversible changes to the magnetic properties of the films are observed. These results suggest that the spin Seebeck effect is ineffective in modifying the precessional dynamics of the present YIG/Cu/Ni81Fe19 samples when subject to ultrafast optical excitation.The authors gratefully acknowledge financial support from Engineering and Physical Sciences Research Council Grant No. EP/J018767/1 and an EPSRC CASE award with Dr. D. Williams of Hitachi Cambridge. H.J.M. acknowledges financial support in the form of a scholarship from “The Establishment of Martyrs of Iraq.

Addressing the Challenges of Tuberculosis: A Brief Historical Account

Tuberculosis (TB) is a highly contagious disease that still poses a threat to human health. Mycobacterium tuberculosis (MTB), the pathogen responsible for TB, uses diverse ways in order to survive in a variety of host lesions and to subsequently evade immune surveillance; as a result, fighting TB and its associated multidrug resistance has been an ongoing challenge. The aim of this review article is to summarize the historical sequence of drug development and use in the fight against TB, with a particular emphasis on the decades between World War II and the dawn of the twenty first century (2000)