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   Table of Contents - Current issue
Coverpage
April-June 2022
Volume 13 | Issue 2
Page Nos. 77-140

Online since Thursday, April 7, 2022

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REVIEW ARTICLE  

Recent advances in remotely controlled pulsatile drug delivery systems p. 77
Al Zahraa Khalifa, Houralaeen Zyad, Hoor Mohammed, Kenda Ihsan, Leen Alrawi, Maryam Abdullah, Ola Akram
DOI:10.4103/japtr.japtr_330_21  
Pharmaceutical technology is drastically developing to enhance the efficacy and safety of drug therapy. Pulsatile delivery systems, in turn, gained attraction for their ability to deliver the right drug amount to the right body site, at the right time which is advantageous over conventional dosage forms. Their use is associated with increased patient compliance and allows on-demand drug delivery as well as customizable therapy. Recent technologies have been implemented to further develop pulsatile delivery systems for more precise determination of the dosage timing and duration as well as the location of drug release. Great interests are directed towards externally regulated pulsatile release systems which will be the focus of this review. The recent advances will be highlighted in remotely controlled delivery systems. This includes electro responsive, light-responsive, ultrasound responsive, and magnetically induced pulsatile systems as well as wirelessly controlled implantable systems. The current status of these technologies will be discussed as well as the recent investigations and future applications.
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ORIGINAL ARTICLES Top

Antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities of “dimethyl dimethoxy biphenyl dicarboxylate” in male Wistar rats p. 83
Heba M. I. Abdallah, Gihan F Asaad, Mahmoud S Arbid, Yousra A Nomier
DOI:10.4103/japtr.japtr_292_21  
Dimethyl dimethoxy biphenyl (DDB) dicarboxylate has been applied as a therapeutic modality for curing liver diseases, particularly hepatitis virus. The objective of this study was to assess the protective potential against Triton X-100 induced abnormal fat metabolism in addition to anti-inflammatory, analgesic, and antipyretic effects of DDB. The anti-inflammatory, antinociceptive, and antipyretic of DDB were investigated through induction of paw edema, pain, and fever in experimental rats. DDB decreased cholesterol and triglyceride contents. DDB resulted in inhibition of inflammation, nociception, and fever in the experimental models. DDB improved lipid profile, as evidence of hypolipidemic potential. It also showed anti-inflammatory, analgesic, and antipyretic properties.
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Synthesis conditions and characterization of superparamagnetic iron oxide nanoparticles with oleic acid stabilizer p. 89
Anggita Dipika Wulandari, Sutriyo Sutriyo, Ratika Rahmasari
DOI:10.4103/japtr.japtr_246_21  
Superparamagnetic iron oxide nanoparticles (SPIONs), part of magnetic nanoparticles, have been widely used in biomedical applications. Biocompatibility and magnetic properties make the SPIONs developed further by a lot of researchers. However, in the synthesis process, SPIONs can run into agglomeration. Oleic acid (OA) is one of the stabilizers to prevent agglomeration. This research aims to optimize the synthesis conditions and characterization of SPIONs with OA as a stabilizer. The synthesis of Superparamagnetic Iron Oxide Nanoparticles-Oleic Acid (SPIONs-OA) was performed using the coprecipitation method and was prepared with the addition of 0.75, 1.5, and 3%v/v OA and stirring rate of 750, 1500, 3000, 6000, 9000, and 12,000 rpm. The characterization of hydrodynamic size and polydispersity index was evaluated by dynamic light scattering. Meanwhile, the crystal structure was observed by X-ray diffraction. Then, Fourier transform infrared spectroscopy (FTIR) was used to analyze structures. The results showed that the hydrodynamic size was dependent on OA concentrations and stirring rate. The addition of 1.5%v/v OA and stirring conditions of 750 rpm resulted in the smallest hydrodynamic size and polydispersity index (83.71 ± 0.70 nm and 0.215 ± 0.01 nm, respectively). Based on the crystal structure analysis, the crystal shape was magnetic cubic, and the size of Fe3O4 crystallite changed from 11.38 to 5.61 nm. The FTIR indicated a strong chemical bond between the hydroxyl group of SPIONs and carboxylic acid of OA. In conclusion, the SPIONs-OA was successfully prepared with 1.5%v/v OA concentrations and a stirring rate of 750 rpm.
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The expression of interleukin-1β and nuclear factor erythroid-2 in the periodontitis after treatment of liquid smoke rice hull p. 95
Ira Arundina, Theresia Indah Budhy, Wisnu Setyari Juliastuti, Meircurius Dwi Condro Surboyo, Anisa Nur Halimah, Putrisa Lestari
DOI:10.4103/2231-4040.321508  
Nonsurgical treatment such as scaling and root planing has been the main therapy of periodontal management. However, some individuals are nonresponsive with only mechanical therapy. Rice hull liquid smoke (RH-LS) with higher of phenolic compound supposed to interfere with inflammation process. Thus, the purpose of this study is to investigate the anti-inflammation properties of RH-LS for chronic periodontitis adjunct therapy by observing the expression of nuclear factor erythroid-2 (Nrf-2) and interleukin-1β (IL-1β). Two groups of Wistar rats were used. Control group was induced by 1 × 109 colony-forming unit (CFU)/ml Porphyromonas gingivalis (PG) and treated with aquadest for 2 and 7 days. Meanwhile, the other group was induced by 1 × 109 CFU/ml PG and treated with RH-LS for 2 and 7 days. Two central incisive/mandibulae were dissected and stained with immunohistochemistry for analyzed the expression of Nrf-2 and IL-1β. Data were then analyzed statistically using independent t-test (P = 0.05). Treatment with RH-LS for 7 days showed lower expression of IL-1β (4.00 ± 1.58) than control group (13.60 ± 2.70) and showed higher expression of Nrf-2 (11.60 ± 1.95) than control group (4.20 ± 1.64) (P = 0.000) (P < 0.05). Treatment of RH-LS for 2 days showed higher expression of Nrf-2 (2.20 ± 1.31) than control group (6.80 ± 1.92) (P = 0.003) (P < 0.05). RH-LS showed anti-inflammation properties by elevating the expression of Nrf-2 and depressing expression of IL-1β in periodontitis induced by PG.
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Determination of strain around distal implants as abutments for partial and fixed implant-supported prostheses with posterior cantilever p. 100
Roodabeh Koodaryan, Neda Yasamineh, Ali Hafezeqoran, Sheida Monem Moharrer, Seyed Gholamreza Noorazar
DOI:10.4103/japtr.japtr_160_21  
This study aimed to compare strain around implants used as abutments for removable partial dentures with wrought wires and fixed partial dentures with ball attachments and fixed dentures with posterior cantilever. An edentulous mandibular model was constructed using epoxy resin with four parallel implants in the area between the two mental foramina. Four strain gauges were attached to the buccal, lingual, mesial, and distal aspects of each implant. One fixed prosthesis with cantilever and two removable partial dentures were considered as prosthetic treatments. A vertical 500-N force was applied with 10-N intervals. The maximum strain in the fixed prosthesis was higher than that of the partial removable denture; in the removable denture with a wrought wire arm, it was higher than that in the denture with a ball attachment (P < 0.001). The lowest rate of strain was recorded on the mesial aspect (P < 0.05). However, the highest rate of strain was recorded on the lingual and distal aspects of the removable denture with a wrought wire in the buccal aspect and the removable prosthesis with the ball attachment on the buccal and lingual aspects (P < 0.05). Finally, despite minor differences in the maximum strain rate in each implant position, the differences were not statistically significant (P > 0.05). Partial removable denture with a ball attachment decreased strain more than that by the removable portal denture with a wrought wire arm. The worst type of prosthesis in terms of the overall strain rate was the fixed prosthesis with cantilever.
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Antidiabetic and antihyperlipidemic effects of Premna spinosa bark in experimental animal models p. 106
Rama Chandra Rout, Prasanna Kumar Panda, Lelin Behera, Santosh Kumar Panda, Gurudutta Pattnaik, Sanjib Bhattacharya, Biswakanth Kar
DOI:10.4103/japtr.japtr_300_21  
The purpose of the study is to evaluate the antidiabetic and hyperlipidemic potential of stem bark extract of Premna spinosa (Lamiaceae), by using streptozotocin (STZ)-nicotinamide (NA)-induced diabetic and triton-induced hyperlipidemic models in albino rats. The blood glucose, total cholesterol, and triglyceride levels were determined in STZ-NA-induced diabetic and triton-induced hyperlipidemic rats, as per the respective protocols. It was found that there is the dose dependent and significant reduction in foregoing parameters on the administration of extract from Premna spinosa stem bark at the doses of 200, 400, and 800 mg/kg body weight to diabetic and hyperlipidemic rats. From these observed results it may be inferred that the stem bark of Premna spinosa possesses remarkable antidiabetic and antihyperlipidemic properties.
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Antibiofilm activity and bioactive phenolic compounds of ethanol extract from the Hericium erinaceus basidiome p. 111
Sari Darmasiwi, Yaovapa Aramsirirujiwet, Ingorn Kimkong
DOI:10.4103/japtr.japtr_1_22  
Biofilm formation has become a serious health and environmental problem. Mushrooms are now considered a valuable source of bioactive compounds with antimicrobial properties. The lion's mane mushroom (Hericium erinaceus [HE]) has been used as an antimicrobial for ulcers and gastritis in East Asian countries. However, studies on the antibiofilm activities of HE basidiome against biofilm-forming pathogenic bacteria and their bioactive compound profiles are still limited. The purpose of this study was to determine the antibiofilm activity of HE and to identify its phenolic compound profile. The HE inhibitory activities against bacterial growth and biofilm formation were performed against Pseudomonas aeruginosa, Salmonella Typhimurium, Proteus mirabilis, and Staphylococcus aureus. Remarkably, P. mirabilis was the most susceptible bacteria to HE. The total phenolic content (TPC) of HE was 1652 ± 1.06 μg/ml, with protocatechuic acid and p-coumaric acid being the most abundant phenolic compounds as determined by high-performance liquid chromatography-mass spectrophotometry (HPLC-MS). This research highlights the possibility of HE as an antibiofilm agent that can be developed as a nutraceutical and natural food preservative.
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Purity of maltose-binding protein – Recombinant streptavidin expressed in Escherichia coli BL21 (pD861-MBP: 327892) p. 117
Toto Subroto, Iman Permana Maksum, Muhammad Yusuf, Sri Agung Fitri Kusuma, Wulan Opratami, Maulida Maharani
DOI:10.4103/japtr.japtr_371_21  
Nearly 95% of streptavidin which is expressed in Escherichia coli found as an inclusion body. Protein expressed in an inclusion body form requires further steps for the folding process related to its purification. Whereas the purity level of the recombinant streptavidin is very crucial mainly for the specification test in diagnostic system. In this study, we designed synthetic gene of streptavidin to be fused with maltose-binding protein (MBP) gene to enhance its solubility when expressed in E. coli BL21 (pD861-MBP: 327892) and purified using amylose resin with gradient column buffer. Based on the SDS-PAGE characterization, the majority of recombinant streptavidin was found in soluble than that of insoluble form. Recombinant streptavidin was found at its suitable size at 56.6 kDa in the soluble protein fraction with a concentration of 537.42 mg/L. The purest fraction of streptavidin recombinant was obtained at the 58th fraction in a concentration of 0.86 mg/L with purity level of 98.77%. Compared to the initial crude protein extract, the level of purity is lower, 6.03%. In summary, the MBP purification method improves the purity level and enhances the solubility of the recombinant streptavidin.
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Demonstration of relative bioavailability of newly developed and innovator drug metaxalone 800 mg in healthy subjects under fed condition p. 123
Socorrina Colaco, N Ramesh, Ramakrishna Shabaraya
DOI:10.4103/japtr.japtr_362_21  
The notable unbiased of this research work was to evaluate the well-being and effectiveness of metaxalone by administering the newly developed test and reference drug. A two-period, two-categorization, crossover bioavailability study in fed conditions. Eleven participants were dosed and completed the trial successfully. The drugs were administered by way of a schedule. Samples collected in both periods for pharmacokinetic evaluation. Plasma samples analyzed using a validated method. Pharmacokinetic parameters for investigational and reference products were calculated using the metaxalone drug concentration and safety of the participants monitored by measurement of vital sign. Relative estimation factors calculated for Cmax, Tmax, area under the curve (AUC) t, AUC inf, K el, half-life, and 90% confidence intervals applied for to check for whether reference and test products are equivalent. The experimental part of the study was completed with no major adversarial event. No losses or stern adverse events transpired throughout the course of the experiment. The assessment product is analogous to reference product in relation to degree and extent of absorption. The outcome of this study indicates the newly developed drug is equivalent to the innovator drug and medication was well tolerated by all participants.
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Hospital preparations of ethanol-free furosemide oral solutions: Formulation and stability study p. 128
Charles Bavouma Sombie, J E Kéré Guetambaba, Hermine Zimé Diawara, Josias Yaméogo, Salfo Ouédraogo, Jonathan Goole, Rasmané Semdé
DOI:10.4103/japtr.japtr_325_21  
Furosemide is a diuretic frequently used in the therapeutic management of edema associated with cardiac, renal, and hepatic failure and hypertension. However, there are a very low number of pharmaceutical dosage forms containing furosemide that are suitable for children under 6- years old. Therefore, there is a real need to develop hospital preparations, especially in the hospital. Four oral pediatric solutions of furosemide (2 mg/Ml) were formulated. Two of those solutions did not contain ethanol. For each formulation, 12 batches of 1600.0 Ml were prepared and packaged in 250.0 Ml brown glass bottles with polypropylene screw caps. The physicochemical properties (visual appearance, pH, osmolarity, drug content) and microbiological quality of the finished product were determined on the freshly prepared solutions and after 90 days of storage at 30°C/65% RH. The physicochemical and microbiological characteristics of the freshly prepared solutions were within the prescribed specifications. After 90 days of storage at 30°C/65% RH, the solutions containing sucrose and those without ethanol showed a slight decrease in pH and furosemide content of about 2.5%–4.5% (w/w). Despite this slight decrease, the characteristics remained within the prescribed specifications. Based on the stability profile of the ethanol-free solution containing sorbitol, it could be implemented in hospitals for the care of pediatric patients.
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Phytochemical, in vitro radical scavenging and in vivo oxidative stress analysis of peppermint (Mentha piperita L.) leaves extract p. 133
Rosmalena , Nabilla Aretharify Putri, Fatmawaty Yazid, Neneng Siti Silfi Ambarwati, Hanita Omar, Islamudin Ahmad
DOI:10.4103/japtr.japtr_16_22  
This current work aims to determine phytochemicals, in vitro radical scavenging, and in vivo oxidative stress reduction activities of peppermint (Mentha piperita L.) ethanolic extract (PEE). The Clule method was used to determine the phytochemical content. An in vitro antioxidant with radical scavenging activity was measured using 2,2-diphenyl-1-picrylhydrazyl. An in vivo antioxidant with oxidative stress reduction was carried out for 10 days on 25 male Sprague–Dawley rats (divided into five groups). Every day, each group was given positive control, negative control, 5, 10, and 20 mg/200 gr of body weight (BW) of the extract. The blood plasma was taken for malondialdehyde analysis. A phytochemical identification of PEE revealed more compounds, such as flavonoids, alkaloids, steroids, essential oils, and tannin. PEE exhibits significant in vitro radical scavenging activity, with an IC50 value of 126.695 μg/mL. In the in vivo antioxidant with oxidative stress reduction experiments, 5 mg/200 gr BW was the most effective dose, as evidenced by a considerable drop in malondialdehyde level (0.312 nmol/mL) after and before treatment. In conclusion, PPE has the potential to be developed as a herbal antioxidant based on in vitro and in vivo test results.
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LETTER TO THE EDITOR Top

Omicron: A variant of concern not a cause of panic p. 138
Shefali Arora
DOI:10.4103/japtr.japtr_14_22  
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