The Principles behind Targeted Therapy for Cancer Treatment

The advent of molecular and genetic advancement in the field of oncology research has led to a shift in the treatment of various forms of cancer from traditional chemotherapeutics to targeted therapy. The principle behind targeted therapy is utilizing therapeutics designed to interfere with specific molecules that have a relatively specific or higher expression profile in cancer cells and are critical for cancer growth and progression. These were designed as mechanistic therapeutics in the form of small molecules and monoclonal antibodies. Currently, they have been modified to incorporate passive or active targeting delivery systems to improve their specific distribution and enhance cytotoxicity towards cancer cells while simultaneously reducing their systemic toxicity profile. Passive targeting employs encapsulated delivery systems to take advantage of the enhanced permeation and retention effect of the tumor microenvironment, while active targeting relies on receptor mediated interactions, such as cell surface ligands conjugated to the therapeutic moiety. A synergistic strategy for cancer therapy is evolving, where precision medicine acts as a diagnostic prerequisite for targeted therapy via prognostic biomarkers and tumor genotyping. Despite the plethora of research undertaken in targeted therapy, limited numbers were approved for clinical use, and significant challenges remain to be addressed

Scabies: Application of the Novel Identify-Isolate-Inform Tool for Detection and Management

Scabies is a highly contagious, globally prevalent, parasitic skin infestation caused by Sarcoptes scabiei var. hominis, also known as the itch mite. There have been outbreaks not only in the developing world, but also in the developed world among refugees and asylum seekers. Once infested with scabies mites, symptomatic patients, as well as asymptomatic carriers, quickly spread the disease through direct skin-to-skin contact. Typically, symptoms of scabies are characterized by an erythematous, papular, pruritic rash associated with burrows. Treatment of scabies involves using topical or systemic scabicides and treating secondary bacterial infections, if present. Given the prevalence and contagiousness of scabies, measures to prevent its spread are essential. Through application of the novel Identify-Isolate-Inform (3I) Tool, emergency medical providers can readily identify risk factors for exposure and important symptoms of the disease, thus limiting its spread through prompt scabicide therapy; isolate the patient until after treatment; and inform local public health authorities and hospital infection prevention, when appropriate. Ultimately, these three actions can aid public health in controlling the transmission of scabies cases, thus ensuring the protection of the general public from this highly contagious skin infestation

An Experimental Investigation of Premixed Combustion in Extreme Turbulence

This work has explored various aspects of high Reynolds number combustion that have received much previous speculation. A new high-Reynolds number premixed Bunsen burner, called Hi-Pilot, was designed to produce turbulence intensities in the extreme range of turbulence. The burner was modified several times in order to prevent boundary layer separation in the nozzle, and a large co-flow was designed that was capable of maintaining reactions over the entire flame surface. Velocity and turbulence characteristics were measured using a combination of Laser Doppler Velocimetry (LDV) and Particle Image Velocimetry (PIV). Flame structure was studied using a combination of formaldehyde (CH2O), hydroxyl (OH), and the CH radical. Planar Laser Induced Fluorescence (PLIF). The spatial Overlap of formaldehyde and OH PLIF qualitatively measures the reaction rate between formaldehyde molecules and OH radicals, and is a measure of the reaction layers of the flame. CH PLIF provides an alternative measure of the reaction zone, and was measured to compare with the Overlap PLIF results. Reaction layers are the full-width at half-maximum of the Overlap or CH PLIF signal, and extinction events were defined as regions where the PLIF signal drops below this threshold. Preheat structures were measured using formaldehyde PLIF, and are defined as beginning at 35% of the local maximum PLIF signal, and continue up to the leading edge of the reaction layer. Previous predictions of regime diagram boundaries were tested at the largest values of turbulent Reynolds number to date. The Overlap and CH PLIF diagnostics allowed extensive testing of the predicted broken reaction zones boundary of Peters. Measurements indicated that all run conditions are in the Broadened Preheat - Thin Reaction layers regime, but several conditions are expected to display a broken reaction zone structure. Therefore the work shows that Peters’s predicted boundary is not correct, and therefore a Karlovitz number of 100 is not a valid criteria for broken reactions in the Bunsen geometry. Several measures of the turbulent burning velocity, including the global consumption speed and the extent of flamelet wrinkling, were measured at these conditions. Reaction layers for the burning velocity measurements were provided by the OH PLIF. The measurements showed that the global consumption speed continues to increase for all levels of turbulence intensity u'=SL. In contrast, the flame surface wrinkling rapidly increases the flame surface area for u'=SL < 10, but the flame surface area does not increase further at larger turbulence intensities. This indicates that the flame is not in the laminar flamelet regime, and the consumption rate per unit of flame surface area must be increased. The turbulent diffusivity is thought to be the mechanism enhancing the consumption rate, which is a scenario first hypothesized by Damköhler. The flame structure and burning velocity measurements motivated the measurements of the evolution of turbulence through regions of very thick preheat layers. This measurement utilized simultaneous PIV and formaldehyde PLIF in order to obtain conditioned statistics of the turbulence as a function of eta, the distance from the reaction layer. Together, the results tell a consistent story, and deepen our understanding of premixed combustion at large turbulent Reynolds number.PHDAerospace EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/137086/1/twabel_1.pd

Experimental Investigation of Premixed Turbulent Combustion in High Reynolds Number Regimes using PLIF

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140710/1/6.2014-0314.pd

The pharmacokinetics and milk residual behaviour of tylosin in lactating Najdi ewes

Summary The objective of this study was to evaluate kinetics and the residual decline of tylosin in milk and plasma of lactating Najdi ewes following single intramuscular injection of tylosin at the dose of 10 mg/kg. Blood and milk samples were collected from the ewes before and at different time intervals after treatment. Tylosin concentrations were determined by microbiological agar plate assay using Bacillus subtilis ATCC 6633 as the test organism. The pharmacokinetic parameters were processed using the methods of least square and statistical moments. The plasma levels of tylosin against time were adequately described by a onecompartment open model. The mean obtained values indicated a fairly low area under the plasma concentration-time curve (AUC) (3.0 µg.h/ml) and the maximum plasma concentration (C max ) of 0.63 µg/ml with T max of 1.33 h. The plasma elimination half-life (t 1/2el ) and the mean residence time (MRT) were 2.3 h and 3.9 h, respectively. A different pattern was shown for milk, in which measurable residual levels are found in all animals up to 72 h after treatment. The mean value of milk AUC was 88.1 µg.h/ml and the t 1/2el was 3.3 h. In vitro mean plasma and milk proteins binding of tylosin were 19.3 and 30.2%, respectively. The milk withdrawal period of tylosin in lactating Najdi ewes should be at least 72 h to avoid risks in consumers

Antiulcerogenic effect of camel milk against ethanol induced gastric ulcers

Abstract The effect of oral administration of raw camel milk (5 ml/kg b.wt.) on ethanol-and aspirin-induced gastric ulcers was tested in rats. Oral administration of camel milk in rats with ethanol-induced gastric ulcer, significantly (P &lt; 0.05) redudced the number of long ulcers, average length of ulcers, ulcer index and the volume of gastric juice. The total protein was significantly (P &lt; 0.05) increased and the pH of gastric juice was not significantly changed. The curative ratio was 70.70% in camel milk treated group compared to 45.12% in ranitidine-treated rats. Oral administration of camel milk in rats with aspirin-induced gastric ulcers exhibited, significantly (P &lt; 0.05), same actions with curative ratio of 65.03% compared to 34.03% in ranitidine-treated rats. In conclusion a significant protective effect of camel milk against ethanol-and aspirin-induced gastric ulcers was reported in rats

Guided optimization of fluid status in haemodialysis patients

Background. Achieving normohydration remains a non-trivial issue in haemodialysis therapy. Guiding the haemodialysis patient on the path between fluid overload and dehydration should be the clinical target, although it can be difficult to achieve this target in practice. Objective and clinically applicable methods for the determination of the normohydration status on an individual basis are needed to help in the identification of an appropriate target weight

Bioimpedance spectroscopy for assessment of volume status in patients before and after general anaesthesia

BackgroundTechnically assisted assessment of volume status before surgery may be useful to direct intraoperative fluid administration. We therefore tested a recently developed whole-body bioimpedance spectroscopy device to determine pre- to postoperative fluid distribution.MethodsUsing a three-compartment physiologic tissue model, the body composition monitor (BCM, Fresenius Medical Care, Germany) measures total body fluid volume, extracellular volume, intracellular volume and fluid overload as surplus or deficit of 'normal' extracellular volume. BCM-measurements were performed before and after standardized general anaesthesia for gynaecological procedures (laparotomies, laparoscopies and vaginal surgeries). BCM results were blinded to the attending anaesthesiologist and data analysed using the 2-sided, paired Student's t-test and multiple linear regression.ResultsIn 71 females aged 45 ± 15 years with body weight 67 ± 13 kg and Duration of anesthesia 154 ± 69 minutes [corrected] duration of anaesthesia 154 ± 68 min, pre- to postoperative fluid overload increased from -0.7 ± 1.1 L to 0.1 ± 1.0 L, corresponding to -5.1 ± 7.5% and 0.8 ± 6.7% of normal extracellular volume, respectively (both pConclusionsRoutine intraoperative fluid administration results in a significant, and clinically meaningful increase in the extracellular compartment. BCM-measurements yielded plausible results and may become useful to guide intraoperative fluid therapy in future studies