Search results for: pharmaceutical markers

Authors: Khairy Mohamed Abdalla Zoheir

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One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid were investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid-treated mice showed a significant decrease in Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also downregulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs was also found to be significantly upregulated in lipoic acid-treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for the therapy of Rheumatoid arthritis.

Keywords: lipoic acid, inflammatory markers, rheumatoid arthritis, qPCR

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Authors: Nicholas Jensen

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As the effort to create new drugs to treat rare conditions cost-effectively intensifies, there is a need to ensure maximum efficiency in the manufacturing process. This includes the creation of ultracompact treatment forms, which can best be achieved via applications of fundamental laws of physics. This paper reports an experiment exploring the relationship between the forms of Newton's 2ⁿᵈ Law appropriate to linear motion and to transversal architraves. The moment of inertia of three discs was determined by experiments and compared with previous data derived from a theoretical relationship. The method used was to attach the discs to a moment arm. Comparing the results with those obtained from previous experiments, it is found to be consistent with the first law of thermodynamics. It was further found that Newton's 2ⁿᵈ law violates the second law of thermodynamics. The purpose of this experiment was to explore the relationship between the forms of Newton's 2nd Law appropriate to linear motion and to apply torque to a twisting force, which is determined by position vector r and force vector F. Substituting equation alpha in place of beta; angular acceleration is a linear acceleration divided by radius r of the moment arm. The nevrological analogy of Newton's 2nd Law states that these findings can contribute to a fuller understanding of thermodynamics in relation to viscosity. Implications for the pharmaceutical industry will be seen to be fruitful from these findings.

Keywords: Newtonian physics, inertia, viscosity, pharmaceutical applications

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Authors: Karishma Chester, Sarvesh Paliwal, Sayeed Ahmad

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Solanumnigrum L. (Family: Solanaceae), is an important Indian medicinal plant and have been used in various traditional formulations for hepato-protection. It has been reported to contain significant amount of steroidal glycosides such as solamargine and solasonine as well as their aglycone part solasodine. Being important pharmacologically active metabolites of several members of Solanaceae these markers have been attempted various times for their extraction and quantification but separately for glycoside and aglycone part because of their opposite polarity. Here, we propose for the first time simultaneous extraction and quantification of aglycone (solasodine)and glycosides (solamargine and solasonine) inleaves and berries of S.nigrumusing solvent extraction followed by HPTLC analysis. Simultaneous extraction was carried out by sonication in mixture of chloroform and methanol as solvent. The quantification was done using silica gel 60F254HPTLC plates as stationary phase and chloroform: methanol: acetone: 0.5 % ammonia (7: 2.5: 1: 0.4 v/v/v/v) as mobile phaseat 400 nm, after derivatization with an isaldehydesul furic acid reagent. The method was validated as per ICH guideline for calibration, linearity, precision, recovery, robustness, specificity, LOD, and LOQ. The statistical data obtained for validation showed that method can be used routinely for quality control of various solanaceous drugs reported for these markers as well as traditional formulations containing those plants as an ingredient.

Keywords: solanumnigrum, solasodine, solamargine, solasonine, quantification

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Authors: Vishvas N. Patel, Mehul Chorawala

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Currently, according to the authors best knowledge there are less effective therapeutic agents to limit intestinal mucosa damage associated with inflammatory bowel disease (IBD). Clinical studies have shown beneficial effects of several probiotics in patients of IBD. Probiotics are live organisms; confer a health benefit to the host by modulating immunoinflammation and oxidative stress. Although probiotics in murine and human improve disease severity, very little is known about the specific contribution of cell wall contents of probiotics in IBD. Herein, we investigated the ameliorative potential of cell wall contents of Lactobacillus casei (LC) in lipopolysaccharide (LPS)-induced murine colitis. Methods: Colitis was induced in LPS-sensitized rats by intracolonic instillation of LPS (50 µg/rat) for consecutive 14 days. Concurrently, cell wall contents isolated from 103, 106 and 109 CFU of LC was given subcutaneously to each rat for 21 days, considering sulfasalazine (100 mg/kg, p.o.) as standard. The severity of colitis was assessed by body weight loss, food intake, stool consistency, rectal bleeding, colon weight/length, spleen weight and histological analysis. Colonic inflammatory markers (myeloperoxidase (MPO) activity, C-reactive protein and proinflammatory cytokines) and oxidative stress markers (malondialdehyde, reduced glutathione and nitric oxide) were also assayed. Results: Cell wall contents of isolated from 106 and 109 CFU of LC significantly improved the severity of colitis by reducing body weight loss and diarrhea & bleeding incidence, improving food intake, colon weight/length, spleen weight and microscopic damage to the colonic mucosa. The treatment also reduced levels of inflammatory and oxidative stress markers and boosted antioxidant molecule. However, cell wall contents of isolated from 103 were ineffective. Conclusion: In conclusion, cell wall contents of LC attenuate LPS-induced colitis by modulating immuno-inflammation and oxidative stress.

Keywords: probiotics, Lactobacillus casei, immuno-inflammation, oxidative stress, lipopolysaccharide, colitis

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Authors: Chand Pasha

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A Simple, accurate and precise spectrophotometric method for the quantitative analysis of determination of 5-aminosalicylic acid is described. This method is based on the reaction of 5-aminosalicylic acid with nitrite in acid medium to form diazonium ion, which is coupled with acetylacetone in basic medium to form azo dyes, which shows absorption maxima at 470 nm. The method obeys Beer’s law in the concentration range of 0.5-11.2 gml-1 of 5-aminosalicylic acid with acetylacetone. The molar absorptivity and Sandell’s sensitivity of 5-aminosalicylic acid -acetylacetone azo dye is 2.672 ×104 lmol-1cm-1, 5.731 × 10-3 gcm-2 respectively. The dye formed is stable for 10 hrs. The optimum reaction conditions and other analytical parameters are evaluated. Interference due to foreign organic compounds have been investigated. The method has been successfully applied to the determination of 5-aminosalicylic acid in pharmaceutical samples.

Keywords: spectrophotometry, diazotization, mesalazine, nitrite, acetylacetone

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Authors: Karthick Dharmalingam, Stalin Ramakrishnan, Haseena Banu Hedayathullah Khan, Sachidanandanam Thiruvaiyaru Panchanadham, Shanthi Palanivelu

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Background: Breast cancer is arising as the most dreadful cancer affecting women worldwide. Hence, there arises a need to search and test for new drugs. Herbal formulations used in Siddha preparations are proved to be effective against various types of cancer. They also offer advantage through synergistic amplification and diminish any possible adverse effects. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio and has been used for the treatment of mammary carcinoma. Objective: To study the restorative effect of Tridham and penta galloyl glucose (a component of TD) on DMBA induced mammary carcinoma in female Sprague Dawley rats. Materials and Methods: Rats were divided into seven groups of six animals each. Group I (Control) received corn oil. Group II– mammary carcinoma was induced by DMBA dissolved in corn oil single dose orally. Group III and Group IV were induced with DMBA and subsequently treated with Tridham and penta galloyl glucose, respectively for 48 days. Group V was treated with DMBA and subsequently with a standard drug, cyclophosphamide. Group VI and Group VII were given Tridham and penta galloyl glucose alone, respectively for 48 days. After the experimental period, the animals were sacrificed by cervical decapitation. The mammary gland tissue was excised and levels of antioxidants were determined by biochemical assay. p53 and PCNA expression were accessed using immunohistochemistry. Nrf-2, Cox-2 and caspase-3 protein expression were studied by Western Blotting analysis. p21, Bcl-2, Bax, Bad and caspase-8 gene expression were studied by RT-PCR. Results: Histopathological studies confirmed induction of mammary carcinoma in DMBA induced rats and treatment with TD and PGG resulted in regression of tumour. The levels of enzymic and non-enzymic antioxidants were decreased in DMBA induced rats when compared to control rats. The levels of cell cycle inhibitory markers and apoptotic markers were decreased in DMBA induced rats when compared to control rats. These parameters were restored to near normal levels on treatment with Tridham and PGG. Conclusion: The results of the present study indicate the antineoplastic effect of Tridham and PGG are exerted through the modulation of antioxidant status and expression of cell cycle regulatory markers as well as apoptotic markers. Acknowledgment: Financial assistance provided in the form of ICMR-SRF by Indian Council of Medical Research (ICMR), India is gratefully acknowledged here.

Keywords: antioxidants, Mammary carcinoma, pentaGalloyl glucose, Tridham

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Authors: Fiston Masudi Tambwe, Lwanga Charles, Arfang Badji, Unzimai Innocent

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The development of maize varieties combining Provitamin A (PVA), high yield, and Striga resistance is an effective and affordable strategy to contribute to food security in sub-Saharan Africa, where maize is a staple food crop. There has been limited research on introgressing PVA genes into Striga-resistant maize genotypes. The objectives of this study were to: i) determine the mode of gene action controlling PVA carotenoid accumulation in Striga-resistant maize, ii) identify Striga-resistant maize hybrids with high PVA content and stable yield, and iii) validate the presence of PVA functional markers in offspring. Six elite, Striga-resistant inbred females were crossed with six high-PVA inbred males in a North Carolina Design II and their offspring were evaluated in four environments, following a 5x8 alpha lattice design with four hybrid checks. Results revealed that both additive and non-additive gene action control carotenoid accumulation in the present study, with a predominance of non-additive gene effects for PVA. Hybrids STR1004xCLHP0352 and STR1004xCLHP0046 - identified as Striga-resistant because they supported fewer Striga plants – were the highest-yielding genotypes with a moderate PVA concentration of 5.48 and 5.77 µg/g, respectively. However, those two hybrids were not stable in terms of yield across all environments. Hybrid STR1007xCLHP0046, however, supported fewer Striga plants, had a yield of 4.52 T/ha, a PVA concentration of 4.52 µg/g, and was also stable. Gel-based marker systems of CrtRB1 and LCYE were used to screen the hybrids and favorable alleles of CrtRB1 primers were detected in 20 hybrids, confirming good levels of PVA carotenoids. Hybrids with favorable alleles of LCYE had the highest concentration of non-PVA carotenoids. These findings will contribute to the development of high-yielding PVA-rich maize varieties in Uganda.

Keywords: gene action, stability, striga resistance, provitamin A markers, beta-carotene hydroxylase 1, CrtRB1, beta-carotene, beta-cryptoxanthin, lycopene epsilon cyclase, LCYE

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Authors: Leyla Sattarzadeh, Maghsoud Peeri, Mohammadali Azarbaijani, Hasan Matin Homaee

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Inflammation by various mechanisms may cause atherosclerosis. Systemic circulating inflammatory markers such as C-reactive protein (CRP), pro-inflammatory cytokines such as Interleukin-6 (IL-6) and adhesion molecules like Intracellular Adhesion Molecule-1 (ICAM-1) are the predictors of cardiovascular diseases. Regarding the conflicting results about the effect of resistance exercise training on these inflammatory markers, the present study aimed to examine the effect of eight week different patterns of resistance exercise training on CRP, IL-6 and ICAM-1 levels in healthy untrained women. 40 volunteered and healthy untrained female university students (aged: 21+ 3 yr., Body Mass Index: 21.5+ 3.5 kg/m2) were selected purposefully and divided into three groups. At the end of training protocol and after subjects drop during the protocol in upper body exercise training (n=11), lower body (n=12) completed the eight week of training period although the control group (n=7) did anything. Blood samples gathered pre and post experimental period and CRP, IL-6 and ICAM-1 levels were evaluated using special laboratory kits, then the difference of pre and post values of each indices analyzed using one way Analysis of Variance (α < 0.05). The results of one way ANOVA for difference of pre and post values of CRP and ICAM-1 showed no significant changes due to the exercise training. But there were significant differences between groups about IL-6. Tukey post- hoc test indicated that there is significant difference between the differences of pre and post values of IL-6 between lower body exercise training group and control group, and eight weeks of lower body exercise training lead to significant changes in IL-6 values. There were no changes in anthropometric indices. The findings show that the different patterns of upper and lower body exercise training by involving the different amount of muscles altered the IL-6 values in lower body exercise training group probably because of engaging the bigger amount of muscles, but showed any significant changes about CRP and ICAM-1 probably due to intensity and duration of exercise or the lower levels of these markers at baseline of healthy people.

Keywords: C-reactive protein, interleukin-6, intracellular adhesion molecule-1, resistance training

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Authors: Faroudja Mohellebi, Fayrouz Khalida Kies, Moncef Rezzik El Marhoun, Feriel Yahiat

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The purpose of this study is to valorize an agro-food waste (orange peels) by its use as an adsorbent in the treatment of water loaded with pharmaceutical micropollutant present in aquatic environments, oxytetracycline. The tests, carried out in batch mode, made it possible to study the influence on the sorptive capacity of calcined orange peels of several parameters: the contact time, the initial concentration of oxytetracycline, the adsorbent dose, and the initial pH of the solution. The pseudo-second-order model is best adapted to represent the adsorption kinetics. The Langmuir model describes the adsorption isotherm of oxytetracycline. The adsorption is favored in a basic environment.

Keywords: adsorption, emerging pollutants, oxytetracycline, water treatment

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Authors: Mohammad Muhebbullah Ibne Hoque, Zheng Jun, Wang Guoying

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Salinity stress is one of the most important abiotic factors contributing to crop growth and yield loss. Exploring the genetic basis is necessary to develop maize varieties with salinity tolerance. In order to discover the inherent basis for salinity tolerance traits in maize, 121 polymorphic SSR markers were used to analyze 163 F2 individuals derived from a single cross of inbred line B73 (a salt susceptible inbred line) and CZ-7 (a salt tolerant inbred line). A linkage map was constructed and the map covered 1195.2 cM of maize genome with an average distance of 9.88 cM between marker loci. Ten salt tolerance traits at seedling stage were evaluated for QTL analysis in maize seedlings. A total of 41 QTLs associated with seedling shoot and root traits were detected, with 16 and 25 QTLs under non-salinity and salinity condition, respectively. And only 4 major stable QTLs were detected in two environments. The detected QTLs were distributed on chromosomes 1, 2, 4, 5, 6, 7, 8, 9, and chromosome 10. Phenotypic variability for the identified QTLs for all the traits was in the range from 6.27 to 21.97%. Fourteen QTLs with more than 10% contributions were observed. Our results and the markers associated with the major QTL detected in this study have the potential application for genetic improvement of salt tolerance in maize through marker-assisted selection.

Keywords: salt tolerance, seedling stage, root shoot traits, quantitative trait loci, simple sequence repeat, maize

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Authors: Ghazi Chabchoub, Mouna Feki, Mohamed Abid, Hammadi Ayadi

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Autoimmune thyroid diseases (AITDs), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are inherited as complex traits. Genetic factors associated with AITDs have been tentatively identified by candidate gene and genome scanning approaches. We analysed three intragenic microsatellite markers in the thyroid hormone receptor associated protein 2 gene (THRAP2), mapped near D12S79 marker, which have a potential role in immune function and inflammation [THRAP2-1(TG)n, THRAP2-2 (AC)n and THRAP2-3 (AC)n]. Our study population concerned 12 patients affected with AITDs belonging to a multiplex Tunisian family with high prevalence of AITDs. Fluorescent genotyping was carried out on ABI 3100 sequencers (Applied Biosystems USA) with the use of GENESCAN for semi-automated fragment sizing and GENOTYPER peak-calling software. Statistical analysis was performed using the non parametric Lod score (NPL) by Merlin software. Merlin outputs non-parametric NPLall (Z) and LOD scores and their corresponding asymptotic P values. The analysis for three intragenic markers in the THRAP2 gene revealed strong evidence for linkage (NPL=3.68, P=0.00012). Our results suggested the possible role of THRAP2 gene in AITDs susceptibility in this family.

Keywords: autoimmunity, autoimmune disease, genetic, linkage analysis

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Authors: J. Zekri, N. Souilah, W. Abdelaziz, D. Alatou

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Our study shall focus on the ability of trees cork oak that showed vis-à-vis sensitivity to climate change, including late spring frosts. The combination of these factors resulted in damage alarmed, therefore forest ecosystems weakened trees that can affect their ability to support other abiotic and biotic stresses, For this we tested its tolerance to thermal variations and cold weather conditions by estimating some stress markers (quantification of proteins, RNA, soluble sugars) that are quantified to evaluate the cold tolerance of seedlings. Sowing of cork oak (Quercus suber L.) is grown in controlled conditions at 25° C ± 2° C in long days 16h. These seedlings are transferred at low temperatures between 5° C and -6° C for a period of 3 hours. Biochemical analyzes were performed in the various organs of the cork oak seedlings. Cool temperatures induced a significant accumulation of proline in different organs of seedlings and the optimum concentrations were observed in the roots with very high concentrations (4 times larger than those of the control). The accumulation of soluble sugars is significantly in stems and roots at 0° C. Protein concentrations are very high in leaves of both growth and high waves in rod at -4° C to -2° C. Tolerance cork oak seems to be at the thermal limit of -2°C. The concentration of these metabolites in the various organs showed the ability oak cork hardening during the winter.

Keywords: climate change, thermal change, semi-aride, biochemical markers, heat stress

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Authors: Mercy Okezue, Kari Clase, Stephen Byrn, Paddy Shivanand

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Medicines regulatory authorities expect pharmaceutical companies and contract research organizations to seek ways to certify that their laboratory control measurements are reliable. Establishing and maintaining laboratory quality standards are essential in ensuring the accuracy of test results. ‘ISO/IEC 17025:2017’ and ‘WHO Good Practices for Pharmaceutical Quality Control Laboratories (GPPQCL)’ are two quality standards commonly employed in developing laboratory quality systems. A review was conducted on the two standards to elaborate on areas on convergence and divergence. The goal was to understand how differences in each standard's requirements may influence laboratories' choices as to which document is easier to adopt for quality systems. A qualitative review method compared similar items in the two standards while mapping out areas where there were specific differences in the requirements of the two documents. The review also provided a detailed description of the clauses and parts covering management and technical requirements in these laboratory standards. The review showed that both documents share requirements for over ten critical areas covering objectives, infrastructure, management systems, and laboratory processes. There were, however, differences in standard expectations where GPPQCL emphasizes system procedures for planning and future budgets that will ensure continuity. Conversely, ISO 17025 was more focused on the risk management approach to establish laboratory quality systems. Elements in the two documents form common standard requirements to assure the validity of laboratory test results that promote mutual recognition. The ISO standard currently has more global patronage than GPPQCL.

Keywords: ISO/IEC 17025:2017, laboratory standards, quality control, WHO GPPQCL

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Authors: Agne Jucyte Cicine, Vytautas Abromaitis, Zita Rasuole Gasiunaite, Mindaugas Zilius

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Pharmaceutical pollution in aquatic environments has become a growing concern. Various active pharmaceutical ingredient (API) residues: hormones, antibiotics, or/and psychiatric drugs, have already been discovered in different environmental compartments. Due to ineffective wastewater treatment technologies, an underestimated amount of APIs can enter the ecosystem by discharged treated wastewater. Especially, psychiatric compounds, such as carbamazepine (CBZ) and venlafaxine (VNX), persist in effluent even post-treatment. Therefore, these pharmaceuticals usually exceed safe environmental levels and pose risks to the aquatic environment, particularly, to sensitive ecosystems such as the Baltic Sea. CBZ, known for its chemical stability and long biodegradation time, accumulates in the environment, threatening aquatic life and human health through the food chain. As the use of medication rises, there is an urgent need for advanced wastewater treatment to reduce pharmaceutical contamination and meet future regulatory requirements. In this study, we tested advanced oxidation technology using ozone to remove two commonly used psychiatric drugs, carbamazepine, and venlafaxine, from biologically treated wastewater effluent. Additionally, general water quality parameters (SPM, DOC, COD) and bacterial contamination were analyzed. Three wastewater treatment plants (WWTPs) were selected to represent varying dominant anthropogenic activities: 1) resort, 2) resort and residential, and 3) residential, industrial, and resort. Wastewater samples for the experiment were collected during the summer season after mechanical and biological treatment and ozonated for 5, 10, and 15 minutes. Pharmaceutical levels in this study exceeded the predicted no-effect concentration (PNEC) of 500 and 90 ng L−1, for CBZ and VNX, respectively in all WWTPs, except CBZ in WWTP 1. Initial CBZ contamination was found to be lower in WWTP 1 (427.4 ng L-1), compared with WWTP 2 (1266.5 ng L-1) and 3 (119.2 ng L-1). VNX followed a similar trend with concentrations of 341.2 ng L-1, 361.4 ng L-1, and 390.0 ng L-1, respectively, for WWTPs 1, 2, and 3. It was determined that CBZ was not detected in the effluent after 5 minutes of ozonation in any of the WWTPs. Contrarily, VNX, was still detected after 5, 10, and 15 minutes of treatment with ozone, however under the limits of quantification (LOD) (<5ng L-1). Additionally, general pollution of SPM, DOC, COD, and bacterial contamination was reduced notably after 5 minutes of treatment with ozone. Although initial pharmaceutical levels exceeded PNECs, indicating ongoing environmental risks, ozonation demonstrated high efficiency in reducing pharmaceutical and general contamination in wastewater with different pollution matrices.

Keywords: Baltic Sea, ozonation, pharmaceuticals, wastewater treatment plants.

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Authors: Maryam Nazari, Majid Karandish, Alihossein Saberi

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Obesity as a global health challenge motivates pharmaceutical industries to produce anti-obesity drugs. However, effectiveness of these agents is remained unclear. Because of popularity of dietary supplements, the aim of this study was tp investigate the effects of Conjugated Linoleic Acid (CLA) and L-carnitine (LC) on serum glucose, triglyceride, cholesterol and weight changes in diet induced obese rats. 48 male Wistar rats were randomly divided into two groups: Normal fat diet (n=8), and High fat diet (HFD) (n=32). After eight weeks, the second group which was maintained on HFD until the end of study, was subdivided into four categories: a) 500 mg Corn Oil (as control group), b) 500 mg CLA, c) 200 mg LC, d) 500 mg CLA+ 200 mg LC.All doses are planned per kg body weights, which were administered by oral gavage for four weeks. Body weights were measured and recorded weekly by means of a digital scale. At the end of the study, blood samples were collected for biochemical markers measurement. SPSS Version 16 was used for statistical analysis. At the end of 8^th week, a significant difference in weight was observed between HFD and NFD group. After 12 weeks, LC significantly reduced weight gain by 4.2%. Trend of weight gain in CLA and CLA+LC groups was insignificantly decelerated. CLA+LC reduced triglyceride level significantly, but just CLA had significant influence on total cholesterol and insignificant decreasing effect on FBS. Our results showed that an obesogenic diet in a relative short time led to obesity and dyslipidemia which can be modified by LC and CLA to some extent.

Keywords: conjugated linoleic acid, high fat diet, L-Carnitine, obesity

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Authors: Jienny Lee, In-Soo Cho, Sang-Ho Cha

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Adult mesenchymal stem cells (MSCs) have been investigated using preclinical approaches for tissue regeneration. Porcine MSCs (pMSCs) are capable of growing and attaching to plastic with a fibroblast-like morphology and then differentiating into bone, adipose, and cartilage tissues in vitro. This study was conducted to investigate the proliferating abilities, differentiation potentials, and multipotency of miniature pig adipose tissue-derived MSCs (mpAD-MSCs) with or without long-term cryopreservation, considering that cryostorage has the potential for use in clinical applications. After confirming the characteristics of the mpAD-MSCs, we examined the effect of long-term cryopreservation (> 2 years) on expression of cell surface markers (CD34, CD90 and CD105), proliferating abilities (cumulative population doubling level, doubling time, colony-forming unit, and MTT assay) and differentiation potentials into mesodermal cell lineages. As a result, the expression of cell surface markers is similar between thawed and fresh mpAD-MSCs. However, long-term cryopreservation significantly lowered the differentiation potentials (adipogenic, chondrogenic, and osteogenic) of mpAD-MSCs. When compared with fresh mpAD-MSCs, thawed mpAD-MSCs exhibited lower expression of mesodermal cell lineage-related genes such as peroxisome proliferator-activated receptor-g2, lipoprotein lipase, collagen Type II alpha 1, osteonectin, and osteocalcin. Interestingly, long-term cryostoraged mpAD-MSCs exhibited significantly higher cell viability than the fresh mpAD-MSCs. Long-term cryopreservation induced a 30% increase in the cell viability of mpAD-MSCs when compared with the fresh mpAD-MSCs at 5 days after thawing. However, long-term cryopreservation significantly lowered expression of stemness markers such as Oct3/4, Sox2, and Nanog. Furthermore, long-term cryopreservation negatively affected expression of senescence-associated genes such as telomerase reverse transcriptase and heat shock protein 90 of mpAD-MSCs when compared with the fresh mpAD-MSCs. The results from this study might be important for the successful application of MSCs in clinical trials after long-term cryopreservation.

Keywords: mesenchymal stem cells, cryopreservation, stemness, senescence

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Authors: Eng Toon Saw, Kun Liang Ang, Wei He, Xuecheng Dong, Seeram Ramakrishna

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Solvent recovery process is receiving utmost attention in recent year due to the scarcity of natural resource and consciousness of circular economy in chemical and pharmaceutical manufacturing process. Solvent dehydration process is one of the important process to recover and to purify the solvent for reuse. Due to the complexity of solvent waste or wastewater effluent produced in pharmaceutical industry resulting the wastewater treatment process become complicated, thus an alternative solution is to recover the valuable solvent in solvent waste. To treat solvent waste and to upgrade solvent purity, membrane pervaporation process is shown to be a promising technology due to the energy intensive and low footprint advantages. Ceramic membrane is adopted as solvent dehydration membrane owing to the chemical and thermal stability properties as compared to polymeric membrane. NaA zeolite membrane is generally used as solvent dehydration process because of its narrow and distinct pore size and high hydrophilicity. NaA zeolite membrane has been mainly applied in alcohol dehydration in fermentation process. At this stage, the membrane performance exhibits high separation factor with low flux using tubular ceramic membrane. Thus, defect free and ultrathin NaA membrane should be developed to increase water flux. Herein, we report a simple preparation protocol to prepare ultrathin NaA zeolite membrane supported on tubular ceramic membrane by controlling the seed size synthesis, seeding methods and conditions, ceramic substrate surface pore size selection and secondary growth conditions. The microstructure and morphology of NaA zeolite membrane will be examined and reported. Moreover, the membrane separation performance and stability will also be reported in isopropanol dehydration, ketone dehydration and ester dehydration particularly for the application in pharmaceutical industry.

Keywords: ceramic membrane, NaA zeolite, pharmaceutical industry, solvent recovery

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Authors: Miao Yang

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PPCPs (pharmaceutical and personal care products) in water, as an environmental pollutant, becomes an issue of increasing concern. Therefore, the techniques for degradation of PPCPs has been a hotspot in water pollution control field. Since there are several disadvantages for common degradation techniques of PPCPs, such as low degradation efficiency for certain PPCPs (ibuprofen and Carbamazepine) this proposal will adopt a combined technique by using CDs (carbon nanodots)/C₃N₄ composite and ultrasonic irradiation to mitigate or overcome these shortages. There is a significant scientific problem that the mechanism including PPCPs, major reactants, and interfacial active sites is not clear yet in the study of PPCPs degradation. This work aims to solve this problem by using both theoretical and experimental methodologies. Firstly, optimized parameters will be obtained by evaluating the kinetics and oxidation efficiency under different conditions. The competition between H₂O₂ and PPCPs with HO• will be elucidated, after which the degradation mechanism of PPCPs by the synergy of CDs/C₃N₄ composite and ultrasonic irradiation will be proposed. Finally, a sonolysis-adsorption-catalysis coupling mechanism will be established which is the theoretical basis and technical support for developing new efficient degradation techniques for PPCPs in the future.

Keywords: carbon nanodots/C₃N₄, pharmaceutical and personal care products, ultrasonic irradiation, hydroxyl radical, heterogeneous catalysis

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Authors: Sheikha Turki Alketbi

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Objectives: 1. Documenting the spontaneous resolution of AML following the initiation of anti-TB therapy. 2. Presenting an uncommon type of relapse in Acute Myeloid Leukemia. 3. Highlighting the role of immune markers in the diagnosis of Leukemia cutis. 4. Exploring and highlighting the possibility of skin relapse as the exclusive manifestation, even when skin involvement is known secondary manifestation in AML. Background: Spontaneous remission of Acute Myeloid Leukemia (AML) is a rare phenomenon that has only been reported in some case reports, usually following severe infections. Some studies have described the occurrence of tuberculosis (TB) infection with AML, usually after starting chemotherapy. Spontaneous resolution of AML after starting anti TB therapy (ATT), without starting chemotherapy has never been described in the literature. Moreover, Leukemia cutis is another rare skin manifestation of Acute Myeloid Leukemia as a result of infiltration of the skin or subcutaneous tissue by leukemic cells, in which can present during, precedes, after or independently of systemic leukemia. Methods: Here, we present a case of a 13-year-old male who presented with fever, weight loss, lethargy, epistaxis, bruising and dry cough and was later diagnosed with AML. Before initiating leukemia treatment, the patient was tested for TB and was found to have active TB infection. His leukemia treatment was postponed to clear the TB infection and he was commenced on ATT. Two months later, repeat blood film and bone marrow biopsy showed resolution of his AML. The patient remained in remission for 1 month, after which he presented with symmetrical blue purple well-defined round indurated plaques on the chest and thighs. Our differentials were leukemia cutis and Kaposi sarcoma. Results: Skin Biopsy with immune markers done, showed a picture of Acute Myeloid Leukemia. Immunohistochemistry (IHC) showed neoplastic cells diffusely and strongly positive for LCA, CD2, CD31, MPO, CD117, Lysozymes and TDT, and moderately positive for CD34, CD99, CD43 and CD6 And patchy for CD68. Ki67 showed 60% proliferation index. They were negative for the remaining markers. This suggested acute myeloid leukemia (AML). Conclusion: In summary, we present a rare case of TB with AML that resolved after treatment of TB with ATT but relapsed later as leukemia cutis. While skin involvement might occur as a secondary manifestation of AML, Skin relapse could be the only one.

Keywords: Leukemia cutis, Leukemia relapse, Acute Myeloid Leukemia, spontaneous resolution of AML

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Authors: D. S. Mohale, A.V. Chandewar

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Study was undertaken to investigate the effect of imipramine on various biochemical parameters and oxidative stress markers in short and long term depression on rats. Rats were subjected for short (21 days) and long term (84 days) social isolation for and checked for depression on force swim test and tail suspension method. Various markers of oxidative stress like lipid peroxidation (LPO), reduced glutathione (GSH), Supersoxide dismutase (SOD), catalase (CAT) and biochemical parameters like Serum glutamate oxaloacetate transaminase (SGOT), Serum glutamate pyruate transaminase (SGPT), and blood glucose were determined in depressed, control, imipramine and Vitamin E treated group. The rats displayed an increase in depression on force swim test and tail suspension method relative to control. There was significant increase in the level of LPO and decrease in the levels of GSH, SOD and CAT after short and long term depression. Increased oxidative stress in depression which may leads to alteration of biochemical parameters. Treatment with imipramine an tricyclic antidepressant significantly decreases in level of LPO, SGOT, SGPT and increase in the levels of GSH, SOD and CAT in long term depression.

Keywords: depression, oxidative stress, lipid peroxidation, reduced glutathione

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Authors: Bashar Al-Sabti, Jehad Harbali

Abstract:

Background: Pyridine is a reactive base that might be used in preparing sitagliptin. International Agency for Research on Cancer classifies pyridine in group 2B; this classification means that pyridine is possibly carcinogenic to humans. Therefore, pyridine should be monitored at the allowed limit in sitagliptin pharmaceutical ingredients. Objective: The aim of this study was to develop a novel ultra high performance liquid chromatography mass spectrometry (UHPLC-MS) method to estimate the quantity of pyridine impurity in sitagliptin pharmaceutical ingredients. Methods: The separation was performed on C8 shim-pack (150 mm X 4.6 mm, 5 µm) in reversed phase mode using a mobile phase of water-methanol-acetonitrile containing 4 mM ammonium acetate in gradient mode. Pyridine was detected by mass spectrometer using selected ionization monitoring mode at m/z = 80. The flow rate of the method was 0.75 mL/min. Results: The method showed excellent sensitivity with a quantitation limit of 1.5 ppm of pyridine relative to sitagliptin. The linearity of the method was excellent at the range of 1.5-22.5 ppm with a correlation coefficient of 0.9996. Recoveries values were between 93.59-103.55%. Conclusions: The results showed good linearity, precision, accuracy, sensitivity, selectivity, and robustness. The studied method was applied to test three batches of sitagliptin raw materials. Highlights: This method is useful for monitoring pyridine in sitagliptin during its synthesis and testing sitagliptin raw materials before using them in the production of pharmaceutical products.

Keywords: genotoxic impurity, pyridine, sitagliptin, UHPLC -MS

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Authors: Micheale Yifter Weldemichael

Abstract:

Sesame (Sesamum indicum L.) is among the most important oilseed crops for its high edible oil quality and quantity. Sesame is grown for food, medicinal, pharmaceutical, and industrial uses. Sesame is also cultivated as a main cash crop in Asia and Africa by smallholder farmers. Despite the global exponential increase in sesame cultivation area, its production and productivity remain low, mainly due to biotic and abiotic constraints. Notwithstanding the efforts to solve these problems, a low level of genetic variation and inadequate genomic resources hinder the progress of sesame improvement. The objective of this paper is, therefore, to review recent advances in the area of molecular breeding and transformation to overcome major production constraints and could result in enhanced and sustained sesame production. This paper reviews various researches conducted to date on molecular breeding and genetic transformation in sesame focusing on molecular markers used in assessing the available online database resources, genes responsible for key agronomic traits as well as transgenic technology and genome editing. The review concentrates on quantitative and semi-quantitative studies on molecular breeding for key agronomic traits such as improvement of yield components, oil and oil-related traits, disease and insect/pest resistance, and drought, waterlogging and salt tolerance, as well as sesame genetic transformation and genome editing techniques. Pitfalls and limitations of existing studies and methodologies used so far are identified and some priorities for future research directions in sesame genetic improvement are identified in this review.

Keywords: abiotic stress, biotic stress, improvement, molecular breeding, oil, sesame, shattering

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Authors: Fumihiko Isada, Yuriko Isada

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The aim of this research is to clarify the difference by industry segment or product characteristics as regards organisation management for an open innovation to raise R&D performance. In particular, the trait of the pharmaceutical industry is defined in comparison with IT component industry segment. In considering open innovation, both inter-organisational relation and the management in an organisation are important issues. As methodology, a questionnaire was conducted. In conclusion, suitable organisation management according to the difference in industry segment or product characteristics became clear.

Keywords: empirical study, industry segment, open innovation, product-development organisation pattern

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Authors: Siwapech Silapaprayoon, Januluk Khanobdee, Sompid Samipak

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Chili peppers are the fruits of Capsicum pepper plants well known for their fiery burning sensation on the tongue after consumption. They are members of the Solanaceae or common nightshade family along with potato, tomato and eggplant. Thai cuisine has gained popularity for its distinct flavors due to usages of various spices and its heat from the addition of chili pepper. Though being used in little quantity for each dish, chili pepper holds a special place in Thai cuisine. There are many varieties of chili peppers in Thailand, and thirty accessions were collected at Rajamangala University of Technology Lanna, Lampang, Thailand. To effectively manage any germplasm it is essential to know the diversity and relationships among members. Thirty-six Inter Simple Sequence Repeat (ISSRs) DNA markers were used to analyze the germplasm. Total of 335 polymorphic bands was obtained giving the average of 9.3 alleles per marker. Unweighted pair-group mean arithmetic method (UPGMA) clustering of data using NTSYS-pc software indicated that the accessions showed varied levels of genetic similarity ranging from 0.57-1.00 similarity coefficient index indicating significant levels of variation. At SM coefficient of 0.81, the germplasm was separated into four groups. Phenotypic variation was discussed in context of phylogenetic tree clustering.

Keywords: diversity, germplasm, Chili pepper, ISSR

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Authors: V. T. Gerov, D. I. Gerova, I. D. Micheva, N. F. Nazifova-Tasinova, M. N. Nikolova, M. G. Pasheva, B. T. Galunska

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Multiple myeloma (MM) is the most frequent plasma cell (PC) dyscrasia that involves the skeleton. Myeloma bone disease (MBD) is characterized by osteolytic bone lesions as a result of increased osteoclasts activity not followed by reactive bone formation due to osteoblasts suppression. Skeletal complications cause significant adverse effects on quality of life and lead to increased morbidity and mortality. Last decade studies revealed the implication of different proteins in osteoclast activation and osteoblast inhibition. The aim of the present study was to determine serum levels of periostin, sRANKL and osteopontin and to evaluate their role as bone markers in MBD. Materials and methods. Thirty-two newly diagnosed MM patients (mean age: 62.2 ± 10.7 years) and 33 healthy controls (mean age: 58.9 ± 7.5 years) were enrolled in the study. According to IMWG criteria 28 patients were with symptomatic MM and 4 with monoclonal gammopathy of undetermined significance (MGUS). In respect to their bone involvement all symptomatic patients were divided into two groups (G): 9 patients with 0-3 osteolytic lesions (G1) and 19 patients with >3 osteolytic lesions and/or pathologic fractures (G2). Blood samples were drawn for routine laboratory analysis and for measurement of periostin, sRANKL and osteopontin serum levels by ELISA kits (Shanghai Sunred Biological Technology, China). Descriptive analysis, Mann-Whitney test for assessment the differences between groups and non-parametric correlation analysis were performed using GraphPad Prism v8.01. Results. The median serum levels of periostin, sRANKL and osteopontin of ММ patients were significantly higher compared to controls (554.7pg/ml (IQR=424.0-720.6) vs 396.9pg/ml (IQR=308.6-471.9), p=0.0001; 8.9pg/ml (IQR=7.1-10.5) vs 5.6pg/ml (IQR=5.1-6.4, p<0.0001 and 514.0ng/ml (IQR=469.3-754.0) vs 387.0ng/ml (IQR=335.9-441.9), p<0.0001, respectively). for assessment of differences between groups and non-parametric correlation analysis were performed using GraphPad Prism v8.01. Statistical significance was found for all tested bone markers between symptomatic MM patients and controls: G1 vs controls (p<0.03), G2 vs controls (p<0.0001) for periostin; G1 vs controls (p<0.0001), G2 vs controls (p<0.0001) for sRANKL; G1 vs controls (p=0.002), G2 vs controls (p<0.0001) for osteopontin, as well between symptomatic MM patients and MGUS patients: G1 vs MGUS (p<0.003), G2 vs MGUS (p=0.003) for periostin; G1 vs MGUS (p<0.05), G2 vs MGUS (p<0.001) for sRANKL; G1 vs MGUS (p=0.011), G2 vs MGUS (p=0.0001) for osteopontin. No differences were detected between MGUS and controls and between patients in G1 and G2 groups. Spearman correlation analysis revealed moderate positive correlation between periostin and beta-2-microglobulin (r=0.416, p=0.018), percentage bone marrow myeloma PC (r=0.432, p=0.014), and serum total protein (r=0.427, p=0.015). Osteopontin levels were also positively related to beta-2-microglobulin (r=0.540, p=0.0014), percentage bone marrow myeloma PC (r=0.423, p=0.016), and serum total protein (r=0.413, p=0.019). Serum sRANKL was only related to beta-2-microglobulin levels (r=0.398, p=0.024). Conclusion: In the present study, serum levels of periostin, sRANKL and osteopontin in newly diagnosed MM patients were evaluated. They gradually increased from MGUS to more advanced stages of MM reflecting the severity of bone destruction. These results support the idea that some new protein markers could be used in monitoring the MBD as a most severe complication of MM.

Keywords: myeloma bone disease, periostin, sRANKL, osteopontin

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Authors: M. Golzade Gangraj, A. Abdi, N. ganji

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Aim: The aim of this study was to evaluate the Effect of aerobic training with Coriandrum sativum extract on selection of oxidative stress markers in diabetic rats. Methods: The population of male Wistar rats is the Pasteur Institute. Forty rats were randomly selected as subjects. After moving the mouse in vitro and stay for a week in a cage for sustainability, were diabetic. Diabetes induced by injection STZ (55 mg per kg of body weight of mice) was performed. According blood glucose was randomly divided into four experimental groups (control, training, extract and training-extract). Extract group consumed 150 mg per kg of body weight per day coriander juice. Training group performed aerobic training (50-55% VO2max). Result: The results showed that aerobic exercise training and coriander seed extract caused a significant increase in total antioxidant; superoxide dismutase and catalase were significantly decreased malondialdehyde. Conclusion: the research findings can be stated that the exercise with coriander seed extract has the ability to inhibit free radicals and can have beneficial effects on the body's antioxidant defense system and reduce oxidative stress in diabetic rats with STZ. Because it improves the body's antioxidant defense by increasing serum levels of antioxidant enzymes.

Keywords: aerobic training, coriandrum sativum, antioxidant, diabetes

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Authors: P. Praveen Kumar, P. Vimal Prabhu, Renu John

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In biology most microscopy specimens, in particular living cells are transparent. In cell imaging, it is hard to create an image of a cell which is transparent with a very small refractive index change with respect to the surrounding media. Various techniques like addition of staining and contrast agents, markers have been applied in the past for creating contrast. Many of the staining agents or markers are not applicable to live cell imaging as they are toxic. In this paper, we report theoretical and experimental results from quantitative phase imaging of yeast cells with a commercial bright field microscope. We reconstruct the phase of cells non-interferometrically based on the transport of intensity equations (TIE). This technique estimates the axial derivative from positive through-focus intensity measurements. This technique allows phase imaging using a regular microscope with white light illumination. We demonstrate nano-metric depth sensitivity in imaging live yeast cells using this technique. Experimental results will be shown in the paper demonstrating the capability of the technique in 3-D volume estimation of living cells. This real-time imaging technique would be highly promising in real-time digital pathology applications, screening of pathogens and staging of diseases like malaria as it does not need any pre-processing of samples.

Keywords: axial derivative, non-interferometric imaging, quantitative phase imaging, transport of intensity equation

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Authors: J. T. Pitale, S. Ghassab, H. Ay, N. Berme

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Biomechanics researchers commonly use marker-based optical motion capture (MoCap) systems to extract human body kinematic data. These systems use cameras to detect passive or active markers placed on the subject. The cameras use triangulation methods to form images of the markers, which typically require each marker to be visible by at least two cameras simultaneously. Cameras in a conventional optical MoCap system are mounted at a distance from the subject, typically on walls, ceiling as well as fixed or adjustable frame structures. To accommodate for space constraints and as portable force measurement systems are getting popular, there is a need for smaller and smaller capture volumes. When the efficacy of a MoCap system is investigated, it is important to consider the tradeoff amongst the camera distance from subject, pixel density, and the field of view (FOV). If cameras are mounted relatively close to a subject, the area corresponding to each pixel reduces, thus increasing the image resolution. However, the cross section of the capture volume also decreases, causing reduction of the visible area. Due to this reduction, additional cameras may be required in such applications. On the other hand, mounting cameras relatively far from the subject increases the visible area but reduces the image quality. The goal of this study was to develop a quantitative methodology to investigate marker occlusions and optimize camera placement for a given capture volume and subject postures using three-dimension computer-aided design (CAD) tools. We modeled a 4.9m x 3.7m x 2.4m (LxWxH) MoCap volume and designed a mounting structure for cameras using SOLIDWORKS (Dassault Systems, MA, USA). The FOV was used to generate the capture volume for each camera placed on the structure. A human body model with configurable posture was placed at the center of the capture volume on CAD environment. We studied three postures; initial contact, mid-stance, and early swing. The human body CAD model was adjusted for each posture based on the range of joint angles. Markers were attached to the model to enable a full body capture. The cameras were placed around the capture volume at a maximum distance of 2.7m from the subject. We used the Camera View feature in SOLIDWORKS to generate images of the subject as seen by each camera and the number of markers visible to each camera was tabulated. The approach presented in this study provides a quantitative method to investigate the efficacy and efficiency of a MoCap camera setup. This approach enables optimization of a camera setup through adjusting the position and orientation of cameras on the CAD environment and quantifying marker visibility. It is also possible to compare different camera setup options on the same quantitative basis. The flexibility of the CAD environment enables accurate representation of the capture volume, including any objects that may cause obstructions between the subject and the cameras. With this approach, it is possible to compare different camera placement options to each other, as well as optimize a given camera setup based on quantitative results.

Keywords: motion capture, cameras, biomechanics, gait analysis

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Authors: Amal Abo El-Maaty, Amira Mohamed, Nashwa Abu-Aita, Hisham Morgan

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For estimating markers of overweight or obesity of brood mares used for riding and training, 17 mares of different body conditions were subjected to blood sampling and ultrasound examination to measure rump fat thickness and monitor ovulation for six consecutive weeks. Also length (L), heart girth (G) and withers height (H) were measured to estimate body weight (BW), body fat %, body fat mass (BFM) and body mass index (BMI). Mares were classified into three groups according to both body condition score (BCS) and rump back fat (BF). Overweight mares (O) were having BCS > 7 and BF thickness >7mm, moderate body condition (M) mares were having BCS >3and ≤7and BF <3and <7mm, and emaciated mares (E) were having BCS ≤3 and BF ≤3mm. glucose, triglycerides, nitric oxide, ovarian, thyroid, insulin, insulin like growth factor-I (IGF-1), and leptin hormones were measured. Results revealed that BCS, G, L, L*G*H, BW, BF, fat %, BFM were significantly (P<0.0001) decreasing linearly from O to E. T4 concentrations of E were significantly high (P=0.04) compared to M and O but T3 concentrations tended to decrease in E (P>0.05). Insulin and IGF-1 concentrations tended to be high in O (P>0.05) and decrease with the decrease of body condition. M had (P=0.007) the highest leptin, but E mares had the lowest P4 concentrations (P=0.01). Concentrations of glucose and NO decreased with the decrease of BCS and BF but triglycerides of O were insignificantly high. In conclusion, exercise could prevent the development of metabolic syndrome in horses and back fat and morphometric measurements were the easiest and simple assessment of overweight and deviation to obesity.

Keywords: body condition score, insulin, leptin, mares, rump fat

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Authors: Maha Al-Ali, Selvakannan Periasamy, Rajarathinam Parthasarathy

Abstract:

Drying temperature is an important factor impacting the physicochemical properties of the dried materials, particularly the pharmaceutical powders. Drying of pharmaceuticals by using microwave radiation is very limited, and the available information about the interaction between the electromagnetic radiations and the pharmaceutical material is still scarce. Therefore, microwave drying process is employed in this work to dry the wet (moisturised) granules of the formulated naproxen-sodium drug. This study aims to investigate the influences of the microwave radiation temperatures on the moisture removal, the crystalline structure, the size and morphology of the dried naproxen-sodium particles, and identify any potential changes in the chemical groups of the drug. In this work, newly formulated naproxen-sodium is prepared and moisturized by wet granulation process and hence dried by using microwave radiation at different temperatures. Moisture analyzer, Fourier-transform infrared spectroscopy, powder X-ray diffraction, and scanning electron microscope are used to characterise the non-moisturised powder (reference powder), the moisturised granules, and the dried particles. The results show that microwave drying of naproxen-sodium at high drying temperature is more efficient than that at low temperatures in terms of the moisture removal. Although there is no significant change in the chemical structure of the dried particles, the particle size, crystallinity and morphology are relatively changed with changing of heating temperature.

Keywords: heating temperature, microwave drying, naproxen-sodium, particle size

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