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Modification of Kynurenine Pathway via Inhibition of Kynurenine Hydroxylase Attenuates Surgical Brain Injury
No full textNeurosurgical procedures result in surgically-induced brain injury (SBI) that causes postoperative complications including brain edema and neuronal apoptosis in the surrounding brain tissue. SBI leads to the release of cytokines that indirectly cause the stimulation of kynurenine 3-monooxygenase (KMO) and the release of neurotoxic quinolinic acid (QUIN). This study tested a KMO inhibitor, RO 61-8048, to prevent postoperative brain edema and consequent neuronal apoptosis in an in vivo model of SBI. A rodent model of SBI was utilized which involves partial resection of the right frontal lobe. A total of 102 Sprague-Dawley male rats (weight 275-325g) were randomly divided into six groups: Sham surgical group, SBI, SBI+DMSO, SBI+RO 61-8048 (10 mg/kg), SBI+ RO 61-8048 (40 mg/kg), and SBI+RO 61-8048 (40 mg/kg)+KAT II inhibitor PF-04859989 (5 mg/kg). RO 61-8048 was administered by intraperitoneal injection after SBI. Postoperative assessment at different time-points included brain water content (brain edema), neurological scoring, and western blot. SBI increased brain water content (ipsilateral frontal lobe), decreased neurological function, and increased apoptotic markers compared with sham animals. Treatment with RO 61-8048 (40mg/kg) reduced brain water content and improved neurological function after SBI. RO 61-8048 increased the expression of kynurenic acid (KYNA) while reducing QUIN and apoptotic markers in the surrounding brain tissue after SBI. These neuroprotective effects were reversed by PF-04859989. This study suggests KMO inhibition via RO 61-8048 as a potential postoperative therapy following neurosurgical procedures
The Effects of Sugars on Lactobacillus Casei Growth
Get PDFThe Western culture tends to deem the Eastern culture as obese and unhealthy due to the large amounts of saturated fats and abundance of sugars that it consumes. Some studies argue that Lactobacillus casei can alter health and researchers are attempting to prove that different sugars, natural or artificial, have different effects on the growth of L. casei [1]. L. casei was chosen as the experimental model due to easily replicable growing conditions and the importance of the bacteria in the gut microbiome.
Sugar-bacteria solutions were created and their turbidities were taken to quantify the amount of bacteria growth after 24 hours of incubation. We hypothesized that the lactose would result in greater proliferation of Lactobacillus casei than glucose, sucrose, and saccharin, respectively. However, we found that all the additional sugars added to the bacteria have an inhibitory effect on the growth of L. casei. By identifying the effects that different sugars have on the concentration of bacteria within the gut microbiome, it will then be possible to manipulate diets and understand the effects that both natural and artificial sugars will have on the body
Coxiella Burnetii Infection Increases Cyclooxygenase Levels in Alveolar Macrophages
No full textCoxiella burnetii is a Gram-negative obligate intracellular pathogen, which spreads via inhalation. Although it initially infects alveolar macrophages, it can cause endocarditis several months to years after infection. This suggests that Coxiella has the ability to survive long-term within the host cells. Our overall goal is to identify how Coxiella achieves this long-term intracellular survival. Previous studies suggest that Coxiella manipulates host lipid metabolism and immune response to establish infection. Our lab has recently shown that Coxiella specifically manipulates metabolism of host lipid storage organelles called lipid droplets (LDs). Further, blocking LD breakdown inhibits bacterial growth suggesting that LD-derived lipids are critical for Coxiella growth. On breakdown, LDs release arachidonic acids, which are converted to prostaglandin E2 (PGE2) by the enzyme cyclooxygenase (COX). PGE2 modulates immune responses during alveolar macrophage infection by other intracellular pathogens like M. tuberculosis, C. pneumoniae to promote bacterial survival. Hence we hypothesize that in Coxiella-infected cells lipid droplet breakdown results in increased PGE2 production to promote bacterial growth. To test this hypothesis, we first analyzed the gene expression of PGE2 synthesis enzyme COX. Compared to uninfected cells, we observed increased cox expression in Coxiella-infected cells. Further, quantitation of total COX enzymatic activity using a fluorescence assay showed increased total COX activity in Coxiella-infected cells. Since COX levels are directly proportional to PGE2 production, our data suggests that Coxiella infection increases PGE2 levels. Ongoing studies are identifying the role of lipid droplets in PGE2 production and the importance of PGE2 during Coxiella infection
Symptom Report of Long-Stay Nursing Home Residents
Get PDFCONTEXT. Prior research has shown that nursing home residents have a significant burden of symptoms including pain, nervous and depressed feelings, fatigue, and lack of energy. OPTIMISTIC is an 8-year initiative funded by the Centers for Medicare and Medicaid Services and is based in Indianapolis. It is designed to reduce avoidable hospitalizations and enhance care in Indiana nursing homes. OBJECTIVE. Our study was a pilot study of OPTIMISTIC that provides baseline data for symptoms reported by stable nursing home residents. SETTING. For the pilot study, research assistants interviewed 42 residents from two different Indianapolis nursing homes. METHODS. To qualify for the study, residents had to be OPTIMISTIC eligible and could not have been acutely ill within the last two weeks. Qualified residents were then selected for interviews based on a randomized prioritized list. Research assistants used the SATISFIE tool to record resident symptom profiles. RESULTS. The results showed that 93% of residents indicated the presence of at least one symptom, and 52% of residents reported that they had at least one symptom that was severe. On average, residents were presenting with about 6.5 symptoms and 2/3 of all residents indicated a depressed mood. CONCLUSIONS. The findings from this pilot study raise awareness of the variety and severity of symptoms experienced by nursing home residents and highlights the need for a more in-depth assessment
Effects of Aging on Muscle Hypertrophy
Get PDFContext: Skeletal muscle is essential for proper bodily functions by playing key roles in strength and movement, and it accounts for roughly 50% of our total body mass. Decreases in total muscle mass or mass-specific function would be expected to have a magnified negative impact. Sarcopenia, an age-dependent loss of motor nerves, leading by necessity to a coincident loss of muscle mass, would have exactly this kind of effect. Results: This age-dependent disorder may be the result of aberrant mTOR signaling, irregular miRNAs content, malnutrition and lack of activity, and age-related inflammation. It may be possible to reduce the effects of sarcopenia via strength training, as well as increasing daily intakes of protein, essential amino acids, and fish oils. Combining the consumption of whey protein, which is high in leucine, and poly-unsaturated fatty acids with strength training resulted in increases in muscle mass and strength. Objective: This review examines the existing causes and effects of age-related sarcopenia, as well as methods that might ameliorate problems associated with age-related sarcopenia
Paclitaxel Dose in iPSC-Generated Sensory Neurons for Ex Vivo Modeling of Taxane-Induced Peripheral Neuropathy
No full textPurpose: To establish an ex vivo model of paclitaxel induced peripheral neuropathy that can be translated clinically using induced human neurons. Experimental Design: Human induced pluripotent stem cells (iPSCs) will be differentiated into mature sensory neurons. After reaching maturation, neurons will be treated with varying doses (0nM, 25nM, 50nM, and 75nM) of paclitaxel to identify the ideal concentration to model paclitaxel-induced peripheral neuropathy ex vivo. Various phenotypic changes will be assessed including changes in morphology, viability, number of dendritic processes, and sensory marker expression patterns. Results: Paclitaxel dosing at 25 nM allows for a 23% reduction in processes length (p=0.04), 50 nM and 75 nM allow for a 51% and 59% reduction in process length (respectively, p\u3c0.0001) while maintaining viable neurons. Conclusion: The administration of 50 nM of paclitaxel to iPSC derived neurons presents an ex vivo method to model paclitaxel induced neuropathy in patients that receive 80 mg/m2 of weekly paclitaxel
