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生物分析および生物医学ジャーナル

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音量 9, 問題 3 (2017)

研究論文

Challenges in Administration of Corticosteroids for the Treatment of Addison’s Disease: A Case Study of Fludrocortisone Acetate

Najim A AL-Awwadi

Fludrocortisone is a known corticosteroid used to control the amount of sodium and fluids in body. Fludrocortisone act by decreasing the amount of sodium that is excreted in your urine. It is indicated to take orally and it is recommended not to stop Fludrocortisone treatment without Physician consent as sudden stoppage leads to several moderate to severe adverse effects.

There are several moderate to severe adverse effects reported with treatment of Fludrocortisone including high Blood Pressure (BP), Heart failure, weakness of muscles, changes in mood and low immune system function. Considering this there is need to develop sustained release formulation as microparticles which help to improve patient compliance by reducing dosage frequency which overall help to reduce side effects reported with Fludrocortisone.

The aim of this research is to develop different formulations of Fludrocortisone (FLU) by using various polymers (poly(ε-caprolactone, PLC), Eudragit® RS and Eudragit® RL) and different processes (oil-in-water (O/W) solvent evaporation methods and suspension-in-oil-in-water (S/O/W) evaporation methods). Small poly(ε-caprolactone (PCL)-based microparticles have successfully developed during study which was leading to good efficiency when it was prepared by oil-in-water (O/W) emulsion method with 7.5 mg/ml of FLU.

研究論文

Type 3 Diabetes Reflects Disordered Lipid Metabolism in the Human Brain Related to Higher Degree of Unsaturated Fatty Acids Composition and is not Related to Body Mass Index

Vincent van Ginneken, Evert de Vries, Verheij E and Jan van der Greef

In this study we investigated lipid profiles of brain of post mortem type 2 diabetes patients T2DM elderly patients in comparison to a Control group (Co) of the “Netherlands Brain Bank” using LCMS techniques. Here we report that brains of these T2DM patients contain more double bonds and consequently are more rigid. In a small cohort (≈200 patients) we prove that these brain diseases are not interrelated with BMI so obesity is not a major cause. The predicted wave of brain diseases of mild-Alzheimer (m-AD), dementia and depression of the “baby boom generation” might be evolved due to the “fatty” and more “rigid” brain structure due to the quality of fats eaten during earlier lifespan. Our major conclusion is that diabetes and its treatment among T2DM patients are more associated with structural disturbances (lipid composition) in the brain than with glycaemic control. Therefore we introduce the new terminology “Type 3 diabetes” (T3DM) referring to the mental disorders as a consequence of a disordered lipid metabolism in the human brain related to higher degree of unsaturated fatty acids composition.

研究論文

On the Futile Existence of DHA, None of EPA and the Predominant Role of the Triacylglycerols (TGs) in the Post Mortem Human Brain: An LCMS Study with Evolutionary Implications

Vincent van Ginneken, Aline van Meerveld, Elwin Verheij and Jan van der Greef

What is known about the brain is a scanty amount of information despite its importance in human evolution. Here we perform based on a holistic Systems Biology lipidomics approach an attempt describing the brain biochemical lipid composition based on the homogenate of a part (gyrus) of the neocortex of post mortem material of the “Dutch Brain Bank” with LCMS techniques. From evolutionary perception the occurrence of the “fish oils” in blood and/ or brain is interesting and their ability to pass the Blood-Brain Barrier (BBB). Both omega-3 “fish oil” Fatty Acids (FA) Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA). EPA and DHA are found in rather high concentrations respectively 0.277% and 0.258% respectively in blood plasma but not in the brain. EPA is not found in grey or white neocortex matter so probably it cannot pass the BBB while this is the case for DHA giving values of respectively ≈0.00015% while Triacylglycerols (TGs) are the major constituent of the human brain with a mean value of the neocortex of ≈72%. We finally conclude the TGs have played a major role in the process of human brain growth and encephalization during course of evolution.

研究論文

A Strategy to Optimize Recovery in Orthopedic Sports Injuries

Michael P Sealy, Ziye Liu, Chao Li, Yuebin Guo, Ben White, Mark Barkey, Brian Jordon J, Luke N Brewer and Dale Feldman

An important goal for treatment of sports injuries is to have as short a recovery time as possible. The critical problem with current orthopedic implants is that they are designed to be permanent and have a high complication rate (15%) that often requires removal and replacement with a second surgery; and subsequently a second rehabilitation cycle. This study was designed to test the feasibility of having a device that could provide the needed mechanical properties, while promoting healing, for a specified amount of time and then degrade away, to shorten the recovery time. The specific strategy was to create a surface layer on a degradable metal alloy with a controllable degradation rate. Previous studies have shown the feasibility of using surface treatments to alter the surface integrity (i.e., topography, microhardness, and residual stress) leading to increased fatigue strength and a decreased degradation rate. This study was an extension of these previous studies to look at the changes in surface integrity and mechanical properties initially as well as the degradation over time for two surface treatments (shot peening and burnishing). Although the treatments improved initial properties and the burnishing treatment slowed degradation rate, the faster degradation of the base material in vitro (compared to previous studies) probably reduced the overall impact. Therefore although the study helped support the feasibility of this approach by showing the ability of the surface treatment to modify surface integrity, initial mechanical properties, and degradation rate; the degradation rate of the base material used needs to be slower and/or the surface treatment needs to create a bigger change in the degradation rate. Further it ultimately needs to be shown that the surface treatment can produce a material that will allow orthopedic devices to meet the required clinical design constraints in vivo.

研究論文

Method Development and Validation for the Determination of Pravastatin in Human Plasma by Lc-Ms/Ms

Lian Chen, Paresh Joshi, Andrii Piatkivskyi, Kalem Aguilar and Jenny Lin

A simple, rapid, sensitive and selective liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for the quantification of pravastatin in human plasma. Pravastatin-D3 was used as an internal standard. The analyte was extracted from human plasma samples by liquid-liquid extraction technique. Due to the presence of isobaric metabolites, 3α-iso-pravastatin and 6-epi-pravastatin, chromatographic conditions were optimized, with a C18 column by using a mixture of 0.1% acetic acid in water and acetonitrile/methanol (43:57, v/v) as the mobile phase at a flow rate of 0.6 mL/min. The calibration curve obtained was linear (r2 ≥ 0.9900) over the concentration range of 0.500-500 ng/mL. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The method was suitable for supporting clinical studies.

研究論文

Serum Amyloid A4 and Ceruloplasmin Evaluated Mastitic Cattle with Escherichia coli or Staphylococcus aureus including Resistant Genes

Verginia Mohamed El-Metwally Farag, Amany Mohamed Abd-El-Moaty, Nermin Awad Ibrahim, Samar Magdy Atwa and Mohamed Abd- EL-Naeem EL-Beskawy

This study investigated the prevalence of an important Gram-negative and a Gram-positive bacterial strain, as well as the test on a few antibiotic resistant genes and sensitivity on the two bacteria. Moreover, the relations of the two microorganisms with some Acute Phase Proteins (APPs) inflammatory marker such as Serum Amyloid A (SAA) and Ceruloplasmin (Cp) in serum and milk were inspected. Out of 120 samples of Mastitic cow’s milk were identified 19.2% Escherichia coli (E. coli) and 14.2% Staphylococcus aureus (S. aureus) single isolates. Isolates of E. coli were completely sensitive to imipenem followed by meropenem then amikacin, enrofloxacin, gentamicin and cefoprazone. Two out of four isolates of multidrug resistance (against cefotaxime, penicillin, cefoprazone and gentamicin) showed positive amplification for beta lactam encoded gene blaTEM. Furthermore two isolates (out of four) resisted tetracycline were positive for TetA (A) gene. In S. aureus isolates, resistance was gradually increased from amikacin, tetracycline, and cefotaxime to oxacillin till reached 100% against penicillin. All analyzed eight isolates of penicillin resistance carried blaZ gene. Likewise, Methicillin A (mecA) gene was positive in six out of eight isolates of oxacillin resistance group. Results of SAA4 and Cp levels were differed in both pathogen groups. For E. coli group, the two levels were significantly increased in serum and only Cp elevated in milk comparing with control group. Conversely, in case of S. aureus, both parameters elevated significantly in milk and only SAA4 level was significant elevated in serum.

In conclusion, resistance to β-Lactam group, methicillin resistant group and tetracycline has reached a critical level in mastitic cattle with E. coli and S. aureus. But still the most effective and available antibiotics were enrofloxacin, amikacin and gentamicin. For diagnosis, SAA4 and Cp level has helped as a rapid tool in differentiation between both organisms.

研究論文

Awareness and Beliefs of Antimicrobial Resistance among Health Professionals Working at Tikur Anbessa Specialized Hospital, Addis Ababa: Ethiopia

Alemseged Beyene Berha, Dugomsa Amin and Minyahil Alebachew

Introduction: Antimicrobial Resistance (AMR) threatens the effective prevention and treatment of an everincreasing range of infections caused by bacteria, parasites, viruses and fungi. In recent years, since the rate at which resistance occurs has outpaced the development of new drug replacements, it has become necessary to use the currently available agents, optimally and appropriately. The aim of this study was to assess the medical staff awareness towards the most common resistant bacteria species, the factors contributing to the lack of awareness, and the possible measures to address the awareness gap.

Methods: A structured questionnaire was administered to 205 health care professionals including physicians, pharmacists, and nurses at Tikur Anbessa Specialized Hospitals, Addis Ababa-Ethiopia.

Results: The study identified that most of the responding physicians and pharmacists considered Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) as the most frequently encountered resistant bacterial species. However, nurses recognized both MRSA and extended-spectrum β-lactamase producing Gramnegative bacilli (ESBL) as the most prevalent resistant species. Majority of physicians (79.2%) and pharmacists (79.9%) reported prolonged hospitalization as a factor likely to contribute to the increased incidence of bacterial resistance. About 66.0% of pharmacists indicated that the use of antibiotics without prescription as a significant reason for the development of bacterial resistance. Most of the physicians (71.4%) reported that appropriate infection control is the most important measure to reduce bacterial resistance.

Conclusion: The findings of this study revealed that there was good awareness of the most common AMR etiologies and their risk factors among the different discipline health professionals. Even though there was a varying level of awareness among the health care professionals. Continuous medical education programs would be desirable to keep the health care professionals updated and diminish the future risk of excessive bacterial resistance.

研究論文

In Vitro Dissolution Study and Assay of Diclofenac Sodium from Marketed Solid Dosage form in Bangladesh

Tania Sultana, Md. Didaruzzaman Sohel, Md. Hassan Kawsar and Rebecca Banoo

The aim of this study is to determine the potency of drug available in our market in Bangladesh. Diclofenac Sodium is a potent Non-Steroidal Anti-Inflammatory Drug (NSAID) and that are widely used and it is an Over the Counter (OTC) drug in Bangladesh. Potency determination was performed to evaluate that the marketed sample comply with the declared specification or not. In vitro Dissolution study was performed to see that if potency is high but the drug is not bioavailable. Hardness is also checked to see that whether it interfere with the dissolution which ultimately effect the bioavailability. In this present study a simple, cost effective and spectrophotometric method for the potency determination of marketed Diclofenac Sodium tablets is used. Four samples were randomly collected from the market and coded as D01, D02, D03 and D04 and the potency determined are 99.30%, 103.38%, 98.22% and 102.16% respectively. Hardness and in vitro dissolution of the above four brands of Diclofenac Sodium tablets were also studied and reported in the paper. After 1 h Dissolution release of DO1, D02, D03 and D04 are 94.16%, 93.97%, 96.94% and 98.5% respectively. From all of the studies it seems that the samples were collected complies with the BP and USP requirements.

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