Stability of Extemporaneously Prepared Sodium Benzoate Oral Suspension

The stability of extemporaneously prepared sodium benzoate oral suspension in cherry syrup and Ora-Sweet was studied. Oral solutions of 250-mg/mL sodium benzoate were prepared in either cherry syrup or Ora-Sweet. To a beaker, 50 grams of Sodium Benzoate Powder USP was dissolved and filtered, the solution was divided equally into two parts, and each aliquot was added into two separate calibrated 100-mL amber vials. In the first vial, cherry syrup was added to make a final volume of 100 mL. In the second vial, Ora-Sweet was added to give a final volume of 100 mL. This process was repeated to prepare three solutions of each kind and all were stored at room temperature. A 250-µL sample was withdrawn immediately after preparation and again at 7, 14, 28, 60, and 90 days for each sample. At each time point, further dilution was made to an expected concentration of 0.25 mg/mL with sample diluent, and the samples were assayed in triplicate by stability-indicating high-performance liquid chromatography. Stability was defined as the retention of at least 90% of the initial concentration. At least 92% of the initial concentration of sodium benzoate in cherry syrup and at least 96% of the sodium benzoate in Ora-Sweet remained throughout the 90-day study period. There were no detectable changes in color and no visible microbial growth in any sample. Extemporaneously compounded suspensions of sodium benzoate in cherry syrup or Ora-Sweet were stable for at least 90 days when stored in a 4-oz amber plastic bottle at room temperature in reduced lighting

Fructose Alters Cell Survival and Gene Expression in Microglia and Neuronal Cells Lines

Purpose: Microglia are macrophages that are found primarily in the CNS and play a crucial role in maintaining a healthy brain by engulfing invading microorganisms, releasing inflammatory mediators, and pruning dead cells. Microglia can become activated in response to certain stimuli which causes them to transition into a pro-inflammatory state, and can sometimes become chronically activated which can result in neuronal damage. Studies have shown a causal relationship between this activation and sugars such as fructose and glucose. We sought to understand the role of sugars in microglial activation and the subsequent effects on neuron health. Methods: Rat microglia (HAPI) and neuronal (B35) cell lines were treated with varying concentrations of fructose (25 mM, 12.5 mM, and 6.25 mM) or glucose (25 mM and 12.5 mM)as a positive control to determine their effects on the cells. Following treatment and incubation for 3 or 24 hours, the cells were analyzed using an MTT assay to measure cell survival or real-time polymerase chain reaction (RT-PCR) to measure gene expression levels. Effects of fructose were measured in HAPI microglia after direct treatment with the sugar. The genes investigated by the RT-PCR in the HAPI cells included: glucose transporter 5 (GLUT5), and the inflammatory markers high mobility group box 1 (HMGB1), and prostaglandin E receptor 2 (Ptger2). To evaluate the effects of microglial activation on neuronal function, the B35 neurons were treated either directly with sugars or with the supernatant collected from fructose-treated HAPI microglia. This allows examination of the effects of soluble neuron-injury factors released by microglia. The genes investigated by RT-PCR in B35 neurons included nuclear factor-κB (NFκB) and enolase 2 (Eno2). Results: Cell survival assays showed that 24-hour direct fructose treatment increased B35 cell survival by up to 13%, while groups treated with microglia supernatant increased cell survival by up to 33%. In HAPI microglia, 3 hours of treatment with fructose caused GLUT5 expression to be suppressed by up to 32% in all treatment groups except for 6.25 mM fructose, while Ptger2 and HMGB1 expression was increased by as much as 65% and 15%, respectively. After 24-hours of treatment with fructose, the HAPI microglia showed a maximum of 80% increased expression of HMGB1, while Ptger2 expression was mostly unchanged. In B35 neurons, 3 hours of treatment with fructose caused a decrease of up to 26% in NFκB and an increase of up to 46% in Eno2 expression. Conclusion: Cell survival results indicate that the microglia may provide a short term protective effect on the B35 neurons. However, data from the gene expression assays show evidence of cellular dysfunction in neurons and pro-inflammatory activity in microglia which may lead to neuronal death on a longer timeline. As seen in the gene expression results, microglia had increased expression of pro-inflammatory genes and B35 neuronal cells had increased expression of markers of cellular damage. Future studies will further explore the effects of fructose on expression of other genes and examine the effects on neuron survival at later time points

Stability of Extemporaneously Prepared Sodium Benzoate Oral Solution

Purpose: Sodium benzoate (NaC7H5O2), a common food preservative, is the salt form of benzoic acid. It is used as an alternative treatment in patients with hepatic encephalopathy or urea cycle disorders as it is believed help stimulate ammonia removal via a non-urea cycle based pathway. Despite its use, sodium benzoate is not an FDA approved medication and has no commercially available oral formulations, although an IV formulation is available in combination with sodium phenylacetate (Ammonul®). The objectives of this study were to prepare a sodium benzoate solution and determine the stability of an extemporaneously prepared oral solution over a 90-day period. Methods: An oral solution of sodium benzoate was prepared and a 1 ml sample was withdrawn from each bottle immediately after preparation and at 7 and 14 days and assayed for drug concentration by stability-indicating high performance liquid chromatography. Stability of sodium benzoate solution will be defined as maintenance of greater than or equal to 90 percent of the initial concentration. Results: The sodium benzoate maintained 96% and 93% of the initial concentrationt at 7 and 14 days, respectively. Therefore, sodium benzoate oral solution in cherry syrup is stable for a minimum of 14 at room temperature

Man-Computer Problem Solving in Real-Time Naval Duels

The development of a new Man-Computer Problem Solving Methodology to be widely and effectively applied by the Navy has been the objective of this Research Project. The basic hypothesis that has been examined is as follows. If an interactive system would be available by which a human problem solver could put together, easily and quickly, a simulation of the problem and quickly perform tests of various solutions, perform an evaluation and then further improve the solution, then large scale economies and improved effectiveness would result. The research reported here may be considered to having taken the empirical approach. An experimental environment was selected, namely a Naval War. An interactive problem solving computer system was designed for this environment. To obtain an indication of the effectiveness of the system required the solution of problems in human engineering, computational methods and strategy in the areas of tracking and navigation, sonar applications and processing, and weapon application. New real-time interactive systems were incorporated to simplify the evolution of new problem solving methodologies

A Man-Machine Competitive Game: A Naval Duel

The research reported here is the development of a man-machine game in which the competitors are the captain of a submarine and the commander of an opposing task force. This naval game has been implemented and tested in the Problem Solving Facility of the University of Pennsylvania under Contract NOnr 551(48) sponsored by the Methodology Division, Office of Naval Research. The broad objective of this research has been to experiment with and develop a man-machine framework in which an executive, scientist or engineer may employ strategies and tactics in an operational environment. A complete functional description of the game will be given in this report. This chapter provides an overview of the game and cites its salient characteristics. Chapter 2 presents the game through a play-by-play record of one competitor in an actual duel. Chapter 3 presents the various aspects of the Problem Solving methodology and developed tactics by means of three annotated duels. This also illustrates the versatility of the game and demonstrates the competitors\u27 capability to interact with the computer. Chapter 4 summarizes our research to date and lists planned refinements to the game. Additional documentation of the game structure is provided in the appendices

Environmental Toxins Linked to Neurodegeneration and Autism Activate the Brain’s Immune System

Microglia are the primary immune cells of the central nervous system and become activated in response to noxious stimuli, leading to a cycle of inflammation and cell death that has been implicated in the development of Parkinson’s disease and autism. This study examines the effects of environmental toxins, at levels commonly found in humans, on microglial cell survival and activation. The toxins used in this study include polybrominated diphenyl ether (PBDE) flame retardants, the food additive propionic acid (PPA), and the organochlorine pesticide dieldrin. These chemicals have been linked to neuronal damage, although their effects on microglial cells have not been fully studied. Our results indicate that microglial cell survival could be decreased by as much as 50% due to exposure to these toxins, without the production of certain cytokines produced by lipopolysaccharide (LPS)-induced activation. These effects are significant as further understanding of the role of microglia in neuronal damage could provide a pharmacologic target for future drug development as well as elucidate the pathology of neurodegenerative diseases

Evidence of Combat in Triceratops

Background: The horns and frill of Triceratops and other ceratopsids (horned dinosaurs) are interpreted variously as display structures or as weapons against conspecifics and predators. Lesions (in the form of periosteal reactive bone, healing fractures, and alleged punctures) on Triceratops skulls have been used as anecdotal support of intraspecific combat similar to that in modern horned and antlered animals. If ceratopsids with different cranial morphologies used their horns in such combat, this should be reflected in the rates of lesion occurrence across the skull. Methodology/Principal Findings: We used a G-test of independence to compare incidence rates of lesions in Triceratops (which possesses two large brow horns and a smaller nasal horn) and the related ceratopsid Centrosaurus (with a large nasal horn and small brow horns), for the nasal, jugal, squamosal, and parietal bones of the skull. The two taxa differ significantly in the occurrence of lesions on the squamosal bone of the frill (P = 0.002), but not in other cranial bones (P.0.20). Conclusions/Significance: This pattern is consistent with Triceratops using its horns in combat and the frill being adapted as a protective structure for this taxon. Lower pathology rates in Centrosaurus may indicate visual rather than physical use o

Did the ancient egyptians record the period of the eclipsing binary Algol - the Raging one?

The eclipses in binary stars give precise information of orbital period changes. Goodricke discovered the 2.867 days period in the eclipses of Algol in the year 1783. The irregular orbital period changes of this longest known eclipsing binary continue to puzzle astronomers. The mass transfer between the two members of this binary should cause a long-term increase of the orbital period, but observations over two centuries have not confirmed this effect. Here, we present evidence indicating that the period of Algol was 2.850 days three millenia ago. For religious reasons, the ancient Egyptians have recorded this period into the Cairo Calendar, which describes the repetitive changes of the Raging one. Cairo Calendar may be the oldest preserved historical document of the discovery of a variable star.Comment: 26 pages, 5 figures, 11 table

The Gut Microbiome in Polycystic Ovary Syndrome and Its Association with Metabolic Traits

Context: Despite the gut microbiome being widely studied in metabolic diseases, its role in polycystic ovary syndrome (PCOS) has been scarcely investigated. Objective: Compare the gut microbiome in late fertile age women with and without PCOS and investigate whether changes in the gut microbiome correlate with PCOSrelated metabolic parameters. Design: Prospective, case-control study using the Northern Finland Birth Cohort 1966. Setting: General community. Participants: A total of 102 PCOS women and 201 age- and body mass index (BMI)matched non-PCOS control women. Clinical and biochemical characteristics of the participants were assessed at ages 31 and 46 and analyzed in the context of gut microbiome data at the age of 46. Intervention(s): None Main outcome measure(s): Bacterial diversity, relative abundance, and correlations with PCOS-related metabolic measures. Results: Bacterial diversity indices did not differ significantly between PCOS and controls (Shannon diversity P =.979, unweighted UniFrac P =.175). Four genera whose balance helps to differentiate between PCOS and non-PCOS were identified. In the whole cohort, the abundance of 2 genera from Clostridiales, Ruminococcaceae UCG-002, and Clostridiales Family XIII AD3011 group, were correlated with several PCOS-related markers. Prediabetic PCOS women had significantly lower alpha diversity (Shannon diversity P =.018) and markedly increased abundance of genus Dorea (false discovery rate = 0.03) compared with women with normal glucose tolerance. Conclusion: PCOS and non-PCOS women at late fertile age with similar BMI do not significantly differ in their gut microbial profiles. However, there are significant microbial changes in PCOS individuals depending on their metabolic health.Peer reviewe