Journal of Pharmaceutical Research International

Published by Sciencedomain International
Online ISSN: 2456-9119
The quality of methods and products are usually influenced by several input factors. Research has recently focused on understanding the effects of multidimensional and interconnected input factors on the results of pharmaceutical products and analytical methods using Design of Experiment (DoE). Furthermore, it examines how DOE may be implemented, both for students and teachers, as well as highlighting historical perspectives on DOE. A good experimental design can help you make the most use of the available resources and make the analysis of the results easier. Collaborations between researchers and practitioners that are pushing the boundaries of experimental design are examined. It provides an overview of the principles and applications of the most common screening and response surface design, as well as creating mixtures designs.
Gene therapy is an emerging concept that gives hope to people with highly fatal conditions. It’s almost three decades since the emergence of the idea of gene therapy. Since then, hundreds of medical trials have been conducted worldwide from which we not only have gained enough knowledge but have experienced the need for it in society. Even though the concept of gene therapy has experienced setbacks, success stories are increasing exponentially, proof of which are recommendations and approvals of gene therapy from various medical associations worldwide. Our knowledge has grown over the years, and during this period, we have come across various safety datahelp help us develop better gene therapy approaches. The chief concept of this procedure is to revamp the vehicles for delivery which typically are nanostructures, plasmids, and viruses. The USA and Europe have been pioneers in gene therapy for a very long period; various reports have come from Asian countries, including India, in recent times. Our knowledge of the concept of gene therapy is increasing day by day. New information and data are being analyzed regularly to help provide gene therapies for different diseases. New research has led to various new drug applications for approval at the FDA. In this review, various points, from the history of gene therapy and its requirement in today’s society to the most recent advances in gene therapy, have been discussed. It also covers the works and advances of gene therapy in India.
Background: It is one of the most common abnormalities of human eyes and its incidence has dramatically risen in incidence in the last few decades. Myopia may lead to irreversible vision loss. A number of studies reflect on the effectiveness of low concentration atropine in controlling myopia. Atropine is used topically as a cycloplegic for the accommodation reflex and as a mydriatic for pupillary dilatation. Since myopia is leading cause of diminution of vision in early childhood, use of atropine (0.01%) in early stages can provide regression in myopic changes in eye. This study aimed to assess the change in spherical equivalent, changes in axial and keratometry values and retinal degenerative changes in cases of myopia treated with low dose atropine. Methodology: The enrolled cases of myopia will undergo thorough ophthalmological examination and will be randomized into intervention and control groups. All cases in intervention group will be treated with low dose atropine (0.01%) eye drops at night and will be followed up every 6 months for examination. The control group will be provided refractive spectacles and also followed up every 6 months. The data from both groups will be compared and analysed. Expected Results: Significant reduction in the progression of Myopia among school going children is expected with administration of 0.01% atropine eye drops. Conclusion: Use of atropine (0.01%) in early stages can provide regression in myopic changes in eye.
Age distribution in group A and B n=130
Gender distribution in group A and B n=130
Duration of symptoms distribution in group A and B n=130
Objective: To compare the efficacy of 2% diltiazem gel with 0.2% glyceryl trinitrate in patients presenting with chronic anal fissure at Tertiary Care Hospital, Larkana. Methodology: This prospective comparative Study was conducted at department of Surgery ward-II Chandka Medical Hospital, Larkana from 14-01-19 to 14-07-19. A total of 130 patients who were treated as OPD cases were included in this study. Each patient detailed history & clinical examination, details of symptomatology was recorded in a epically diagnosed proforma. These patients were randomly divided in two equal groups i-e group A 65 patients and group B 65 patients. Group A patients were treated with 02% glyceryl trinitrate and group B patients were treated with diltiazem gel 02%. All the patients of group A & B were followed up to 02 months after start of leadema as a OPD cases. Results: A total of 130 patients (65 each in 2% diltiazem gel with 0.2% glyceryl trinitrate group) were included. Mean age in both groups was 42.56±3.91 and 41.71±4.01. 46 (70.8%) and 19 (29.2%) were male and female in Group A and 39 (60%) and 26 (40%) were male and female in Group B. Efficacy of 2% diltiazem gel with 0.2% glyceryl trinitrate in patients presenting with chronic anal fissure was 76.9% and 50.8% respectively. Conclusion: DTZ (2%) and GTN (0.2%) are equally effective in healing anal fissures. DTZ is better than GTN as it causes less side effects, low recurrence rate, healing rate and therefore better compliance.
Objective: To determine the effect on intraocular pressure following primary Trabeculectomy with MMC 0.2% versus Trabeculectomy without MMC in Primary Open Angle Glaucoma. Study Design: This is a prospective and experimental Study. Setting: Study carried out at Ophthalmology Department, Shaheed Mohtarma Benazir Bhutto Medical University Larkana, from 01-03-2020 to 31-08-2020 (06 Months). Materials and Methods: The patients with primary open angle glaucoma were selected from glaucoma clinic after taking careful history and clinical examination. Patients selected for trabeculectomy into two groups. Group A includes 43 patients while Group B also includes 43 patients. Among Group A patients adjunctive MMC 0.2mg/ml for a period of 3 minutes was used during trabeculectomy as a primary procedure (Test Group) while Group B patients were operated without MMC 0.2% (Control Group). Follow-up period of 06 months was observed in both groups. The span of study was from 01-03-2020 to 31-08-2020. Results: The total of 86 Eyes of 86 patients of POAG were included in this study. Group A patients were operated for trabeculectomy with MMC while group B patients were operated for trabeculectomy without MMC. The mean IOP before surgery of Group-A was 25.39±2.42 mmHg while in Group-B it was 26.23±4.23mmHg. At day 1 of surgery in Group-A patients IOP was 13.20±3.05 mmHg while in Group-B patients IOP, was 14.09±4.04 mmHg. After 3 months in Group-A, IOP was 13.04±3.81 mmHg in Group-B IOP was 14.01±4.18 mmHg. Out of 43 patients in Group-A, 41(95.3%) were succeeded while in Group-B, 39(90.7%)were succeeded. Significant result was found for IOP reduction after 6 months of surgeryin group-A IOP was 13.48 + 2.86 mmHg while in group-B, IOP was 15.09 ±2.64 (P=0.754). Conclusion: Trabeculectomy with MMC as a primary procedure seems to be more effective than trabeculectomy without MMC.
Aim: Articaine, bupivacaine, lignocaine are amide type of local anesthetic agents, which are of almost equal potency. However, lidocaine is considered the gold standard and is the most widely used anesthetic agent because of its potency, safety, and efficiency. Articaine is fast acting and bupivacaine is long lasting local anaesthesia. The aim of this clinical study was to evaluate and compare the clinical anesthetic efficacy of 4% articaine and 0.5% bupivacaine and 2% lignocaine in therapeutic orthodontic extractions. Materials and Methods: A 150 healthy patients, requiring Maxillary premolars extraction for orthodontic reasons were included. Patients were categorized into three groups (4% articaine and 0.5% bupivacaine, 2% lignocaine) in a crossover manner. Subjective and objective observations recorded that include age, gender, and pain score using visual analog scale. At the first appointment, both upper premolars were extracted on one or two sides of the jaws. Each patient was evaluated using a visual analogue scale. Results: The results showed that 0.5% Bupivacaine had significantly faster onset of action and lower visual analogue scores when compared with articaine and lignocaine. However, the duration of analgesia and need of first rescue analgesic medication was longer in the bupivacaine group. Conclusion: Within the limitations of study we found that Bupivacaine has the best anaesthetic effect with low pain scores followed by Articaine and followed by Lignocaine. Bupivacaine is an alternative local anaesthetic drug for performing therapeutic orthodontic extractions.
Background: Disinfection of dental cast is very important because it can cause cross-infection from patients to clinicians and lab personnel. This study aimed to evaluate the effect of addition of 0.5% of chloramine-T as disinfectant in type III gypsum product on its setting time and abrasion resistance. Objectives: 1. To evaluate the effect of Chloramine-T on setting time of type III gypsum product. 2.To evaluate the effect of Chloramine-T on abrasion resistance of type III gypsum product. 3. To compare the mentioned properties with control group of type III gypsum product without Chloramine-T. Methodology: This is an invitro study, sample size is 140. We will be testing for setting time with the help of Vicat needle apparatus and abrasion resistance will be tested with the help of two body wear testing apparatus. This study will be conducted under 4 groups: Group1- Control group for setting time, Group2- Experimental group for setting time, Group3- Control group for abrasion resistance, Group 4- Experimental group for abrasion resistance. Expected Result: It is expected that this study would result in forming a type III gypsum product incorporated with Chloramine-T, thus eliminating the need for any additional steps for disinfecting casts and ultimately preventing cross-infection. Conclusion: Incorporating Chloramine-T can be an efficient method of disinfecting gypsum without adversely affecting the product's mechanical and physical properties.
The sensory motor block for ropivacaine starts at 6.4 minutes and similarly for bupivacaine is 3.32 minutes. The sensory block for ropivacaine is from ranges from T8-T12 and for bupivacaine its T4 - T8 level. The time taken for motor block is 203.8 and for group R its 142.9min. In group B, the mean value of time taken for two segment regression is 97.9 minutes. The time taken for group R to regress is 63.7. In Group its 4. 70 minutes. In Group R the mean onset of motor block is 9.40 minutes.
Background: Mandibular third molars (M3M) are the most common impacted teeth in the human dentition. Removal or extraction of these teeth is frightening for the patients owing to the perception of pain. As a result, pain control mechanism like anesthesia is the major factor that needs to be executed appropriately. Using newer local anesthetic drugs minimizes side effects and drug interactions. Levobupivacaine (Levo) is a congener of bupivacaine thereby minimizing the cardiotoxic effects of bupivacaine. Dexmedetomidine (Dex) is an alpha agonist which alongwith Levo is capable of providing prolonged duration of anesthesia decreasing the need for rescue analgesics. Aim: This study will compare the anesthetic effectiveness between Levo and Levo alongwith Dex during the extraction of impacted M3M. Methodology: A total of 50 consecutive systemically healthy patients requiring unilateral surgical extraction of impacted M3M with similar orientations will be divided into two groups randomly, one group (L) will receive nerve block with levo while the second group (LD) will receive Levo plus Dex during the extraction procedure. Results: ‘Students t-test’ will be used to analyse and evaluate. The patients will be evaluated based on different parameters. The patient will be asked to reciprocate about the first bout of pain experience based on the Visual Analog Scale that will be handed over to patient after the procedure. The other parameters that will be evaluated are Onset on Anesthesia, Depth of Anesthesia, Hemodynamics, Oxygen saturation level, Sedation level and duration of post-operative analgesia. The patient will be evaluated over the time duration after which the patient had to take a rescue analgesic. Conclusion: Levo with Dex is more efficient than Levo in providing prolonged duration of anesthesia and has prolonged duration of postoperative analgesia.
Background: Spinal anaesthesia is a form of local anaesthesia, wherein conduction block of nerve roots is done with the aid of injecting a small dose of local anaesthesia into the subarachnoid space via a lumbar puncture in left lateral position in midline at L3 L4 interface. Drug is given after confirming free flow of CSF. Local anaesthetics work for a short duration and adjuvants are used for prolongation of postoperative analgesia. Ropivacaine, a brand new amide local anaesthetic, accepted via FDA IN 1997 and using it extensively in India since 2009. Ropivacaine due to its excessive Pka and decreased lipid solubility has received popularity. This study has been planned to compare the effects of injection Dexmedetomidine & injection Fentanyl as an Adjuvant to Intrathecal isobaric Ropivacaine 0.75% for lower abdominal surgeries. Materials and Methods: This will be a Comparative Experimental Prospective Study conducted at Anesthesiology department of AVBRH, Wardha. 80 patients will be randomized into two groups. One group will receive 3 ml of 0.75 percent isobaric ropivacaine with dexmedetomidine 10 mcg (Group RD). Another group will receive 20 mcg of fentanyl (Group RF) intrathecally for lower abdominal surgeries. Data on block characteristics, hemodynamic changes, and side effects will be collected and compared for the two groups. Expected Results: Clinically significant results are expected in terms of mean time needed and Mean of total sensory block length in Group RD compared to Group RF. Conclusion: Addition of 10μg dose of dexmedetomidine to 3ml of 0.75 percent isobaric ropivacaine produces earlier sensory blockade, prolonged sensory and motor blockade and improved sedation and post-operative analgesia.
Two different regimes propofol-normal saline vs propofol -ephedrine in prevention of hypotension during induction of anaesthesia, significant decrease in Systolic blood pressure (P<0.001) in both groups (both fluid and non-fluid groups) after induction of anaesthesia with propofol was observed. The incidence of hypo-tension was significant in control and crystalloid group when compared with ephedrine group. Systolic blood pressure decreased in all three groups and decrease in Systolic blood pressure at 2min, 3min and 5min with P values. 0.010, 0.00, 0.000 respectively. Also decrease in Mean Arterial pressure in P group when compared with E-group at 1, 2, 3, 4, and 5min with P values 0.038, 0.02, 0.012 and 0.029 respectively.
Background: This study was aimed to determine the children's' blood sugar level in fluid therapy with DSS (dextrose saline serum), RS (ringer serum) and NS 0.9% serums (normal saline 0.9%) and its relationship with the depth of anesthesia in elective surgery. Method: This double-blind experimental study was performed with 90 children referred to the surgical ward, including: group A (receiving DSS), group B (receiving NS 0.9%) and group C (receiving RS) that the blood sugar of each group in 5 steps was measured: half an hour before induction of anesthesia, during induction of anesthesia, half and one hour after induction of anesthesia and after complete awakening in recovery. In addition, the monitoring the vital signs, measuring depth of anesthesia, pulse oximetry and electrocardiogram were performed for all groups. Results: The results showed that the mean blood sugar in the 5 steps measured had a significant difference in three groups under study (P <0.05). The mean blood sugar in the group receiving DSS was significantly higher than the two groups receiving RS and NS 0.9%. Also the mean depth of anesthesia in three groups did not show a significant difference. Conclusion: Finally, according to this study, the use of DSS from the beginning of anesthesia, RS half an hour after the start of anesthesia and NS 0.9% one hour after the start of anesthesia can increase blood sugar in children. Therefore, the use of DSS is not recommended due to the stressful nature of anesthesia and operating room and the possibility of hyperglycemia.
Purpose: In this study, development of a new analytical method for the evaluation of 4-Hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (Meloxicam) by reverse phase HPLC was carried out. The basic aim of this research was to develop and validate a simple, precise, accurate and sensitive method for qualitative and quantitative analysis of Meloxicam in pharmaceutical raw material and its dosage forms. The existing reported method (BP) for the analysis of Meloxicam is potentiometric method which is an old, lengthy and tedious method. Methods: In the new method of reverse phase HPLC, C18 column was used while the mobile phase was acetonitrile and methanol (70:30). The flow rate of mobile phase was 0.6 ml/min and retention time was found to be 1.5min. Separately equal volume of standard solution and sample solutions in HPLC vials were injected in auto sampler compartment of HPLC in six replicates. Chromatogram and peak areas of Meloxicam in standard and sample solutions of different concentrations were recorded. Results: This method was later validated in different ways by which the calibration curve proved to be linear with linearity coefficient of 0.999 over the range of 100 to 600ppm. The precision was equivalent to 0.0003%. The LOD and LOQ were 0.0003ug/ml and 0.001ug/ml respectively. The system also showed accuracy over the range of 95 to 99%. Conclusion: Hence, this method proved to be an alternative to the existing reported method of potentiometric titration because the new method showed accuracy, reproducibility and sensitivity.
10-(2-hydroxyphenyl)-hexahydro acridinediones were treated with chloroacetyl choloride to give 10-(2-chloroacetyloxyphenyl) hexahydro acridinediones, which were treated with NaN3 in acetone followed by reaction with DMAD yielded 10-[2-(1-triazolo-4,5-dicarboxymethyl)acetyloxyphenyl]-3,4,6,7,9,10-hexahydro-1,8-(2H,5H)- acridinediones.
Aims: Glucokinase (GK) is a cytoplasmic enzyme that metabolizes the glucose to glucose- 6-phosphate and supports the adjusting of blood glucose levels within the normal range in humans. In pancreatic β-cells, it plays a leading role by governing the glucose-stimulated secretion of insulin and in liver hepatocyte cells, it controls the metabolism of carbohydrates. GK acts as a promising drug target for the treatment of patients with type 2 diabetes mellitus (T2DM). Study Design: In the current study, the goal is to identify new substituted benzamide derivatives and test them via molecular docking as possible anti-diabetic drugs. Place and Duration of Study: The present work has been carried out at S.N.J.B’s S.S.D.J. College of Pharmacy, Neminagar, Chandwad, Nashik, Maharashtra, India during the time period of December-2020 to February-2021. Methodology: This work involved designing novel methyl 2-((4-(benzamido)phenyl)sulfanyl)-1,2,3,4-tetrahydro-6-methylpyrimidine-5-carboxylate derivatives and their screening by molecular docking studies to determine the binding interactions for the best-fit conformations in the binding site of the GK enzyme. Autodockvina 1.1.2 in PyRx 0.8 was used to perform the docking studies of all the designed novel derivatives and native ligand against the crystal structure of GK. Based on the results of docking studies, the selected molecules will be tested for their antidiabetic activity in the animal models. Results: Amongst the designed derivatives, compounds A2, A3, A8, A10, A11, A13, A14, A16, A17, and A18 have shown better binding free energy (between -8.7 to -10.3 kcal/mol) than the native ligand present in the enzyme structure. In present investigation, many molecules had formed strong hydrogen bond with Arg-63 which indicate the potential to activate GK. Conclusion: From above results it has been observed that these designed benzamide derivatives have potential to activate the human GK which enables us to proceed for the syntheses of these derivatives.
A series of 1- benzyl-5-methyl 1,2,3 triazole pyrimidine , 1- benzyl-5-methyl 1,2,3 triazole pyrazole were synthesised by using intermediate as phenyl Substituted prop-2-en-1-one .We obtained pyrazole when we treated propenones by using hydrazine hydrate and we obtained pyrimidine by using urea and thiourea. Conformations of the compounds were done by 1HNMR and C13 NMR analysis and these compounds were screened for antimicrobial activities. Graphical Abstract
General structure of 2-substituted-5-[(1H-benzimidazol-2yl)methyl] azole derivatives 2. MATERIALS AND METHODS
Designed Series (A1-A12) with the substituents
Dock score of designed compounds
Interactions of the designed compounds, original substrate and reference ligand with PTR 1
Drug likeness properties of the series using Molinspiration software
Aims: Design and in silico studies of 2,5-disubstituted triazole and thiadiazole derivatives as Pteridine Reductase 1 inhibitors. With a view to develop effective agents against Leishmaniasis, 2-substituted-5-[(1H-benzimidazol-2yl) methyl] azole derivatives (A1-A12) were designed against the target enzyme Pteridine reductase 1. Methodology: The series was designed by targeting Pteridine reductase 1 which is an enzyme responsible for folate and pterin metabolism. Based on thorough study of the enzyme structure and structural features of ligands required for optimum interaction with the enzyme, a series of 12 compounds consisting of 2,5-disubstituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives was designed. In silico studies were carried out which included docking studies (using V Life software) to understand binding of the compounds with enzyme PTR1, ADMET studies, drug likeness studies for physicochemical properties and bioactivity studies to understand the possible mechanism of action of the compounds. These studies were undertaken using online softwares, molinspiration and admetSAR web servers. Results: Compounds A10 and A12 gave the best docking scores of -59.9765 and -60.4373 respectively that were close to dihydrobiopterin (original substrate). All the compounds complied with Lipinski’s rule of five. Most of the compounds displayed favorable ADMET properties. Conclusion: The 2,5-disubstituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives exhibited good binding affinity for PTR1 enzyme (PDB code: 1E92). The docking scores indicated that enzyme binding may be governed by the nature and size of the substituents on the azole ring. The compounds display well-defined drug-like and pharmacokinetic properties based on Lipinski’s rule of five with additional physicochemical and ADMET parameters. Bioactivity studies suggested the possible drug mechanism as enzyme inhibition. Hence, this study provides evidence for consideration of valuable ligands in 2,5-disubstituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives as potential pteridine reductase 1 inhibitor and further in vitro and in vivo investigations may prove its therapeutic potential.
Aims: To synthesize some phthalimides derivatives and evaluate the compounds for their possible biological properties. Methods: The substituted phenylisoindoline-1,3-dione were synthesized from the reactions of N-phenyl phthalimide with different substituted aromatic aldehyde. The synthesized compounds were characterized using nuclear magnetic resonance spectroscopic analysis. The acetylcholinesterase and butyryl cholinesterase inhibitions were determined by Spectro photochemical analysis of acetylthiocholine and butyryl choline chloride. Results: Compounds 6 (IC50 = 30±3 µg/mL) and 4 (IC50 = 141±60 µg/mL) were found to be the most active inhibitors against acetylcholinesterase, while compounds 4 (IC50 = 102±10 µg/mL), 5 (IC50 = 105 ± 20 µg/mL) and 2 (IC50 = 190 ± 10 µg/mL), were found to be most active inhibitor against butyryl cholinesterase. Conclusion: The considerable acetylcholinesterase and butyryl cholinesterase inhibitory activities of the synthesized compounds makes them good candidates for the development of selective acetylcholinesterase and butyryl cholinesterase inhibitors.
Aim: Nicotine Substituted 1,3,4 Oxadiazole and pyrazole moieties were integrated by utilizing hydrazide as halfway .Oxadiazole were acquired by two techniques one is by utilizing PoCl3 within the sight of fragrant corrosive ,other is by utilizing carbon disulphide in the presence ofpotassium hydroxide as an impetus .Pyrazoles were likewise gotten by ehtylacetoacetate we acquired unrefined item and again it was recrystallized by utilizing alcohol.All incorporated mixtures were evaluated for Antibacterial activity and enaminones showed promising action against standard medication ciprofloxacin. Methods: TLC on silica gel G was used to check for homogeneity of the title compound. H NMR, Mass, and IR Spectra were used to characterise these compounds, and their antibacterial activity was tested. Results: All of these compounds, including nicotine substituted ester, hydrazide, 1,3,4 Oxadiazole, and pyrazole, showed antibacterial activity. The maximum activity of enaminones was comparable to that of the standard drug ciprofloxacin (5mcg). Compound1 showed potent antimicrobial activity Conclusion: In the zone of inhibition studies, all six samples at MIC concentrations showed reasonable antimicrobial activity Compound1 showed very good antimicrobial activity
Background: Synthetic chemistry has always served as a back bone to the medicinal and pharmaceutical chemistry in terms of drug development and drug optimization. It helped in a great deal in finding new lead compounds and synthesizing new drugs. A new molecule N-(2,6-Dimethylphenyl)-2-{[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl] sulfanyl} acetamide, was synthesized from the fusion of Indole acetic acid with 1,3,4-oxadiazole. This pharmacologically active entity lacks a suitable method for its analysis. Aim: The present research aimed to develop a UV visible spectroscopic method for the purpose followed by its validation according to ICH guidelines. Methodology: The method was developed at 225 nm (λmax). Then the accuracy, precision, sensitivity (Limit of detection & Limit of quantification), specificity, robustness and ruggedness were calculated. The analyte was exposed to multiple stress conditions to figure out method’s specificity. Results: The developed method showed the linearity within a range (0.5 – 50 µg/mL) with correlation coefficient (R2) = 0.9997. The accuracy of the developed method was figured out by recovery analysis and it was within 95.556 – 104.321 %. The precision analysis i.e. interday (0.505591 %), intraday (0.231661 %) and repeatability (0.06478 %), were within the acceptance criteria viz. % RSD less than 2 % and LOD & LOQ were found to be 0.523356 and 1.58598 µg/mL. All the validation parameters were within the acceptance limits making the method unique and acceptable. In addition to that it was found to be easy, reliable and analyst friendly (ruggedness, 0.520889 %). The analyte when exposed to stress conditions viz. acidic (0.1N H2SO4) and basic (0.1N NaOH) environment, oxidative stress (3 % H2O2), UV light and altered temperature and humidity (80 ºC+75% RH) for 24 hr, it was found deteriorated. The analyte was 65.56 % degraded in acidic, 39.63 % in basic, 45.18 % under oxidative stress and 61.85 % under altered conditions of temperature and humidity. There was a complete loss of analyte (87.78 %) when exposed to UV light. Conclusion: The results clearly states that the method is simple, sensitive, specific, precise and accurate, thus can be employed for the quantitative estimations of the analyte.
Persistent and uncontrolled use of antibiotics results in development of bacterial resistant. The situation is getting worsen day by day and scientists are investigating thousands of potentially active drugs like molecule in laboratories around the world every day in search of effective antibiotics. During last decade considerable attention was given to five-member heterocyclic moieties while designing new antimicrobial agents. One of important heterocycle is five-membered 1,3,4-thiadiazole with unique bioisosteric properties displaying unusually wide spectrum of biological activities. This comprehensive review represent the recent 1,3,4-thiadiazole and its derivatives, which can be considered as potential antimicrobial agents in the period of 2015 and onwards. This review may help the medicinal chemists to develop new leads possessing 1,3,4-thiadiazole nucleus with higher efficacy and reduced side effects.
A new class of potentially biologically active new 1,3,4-thiadiazol derivatives have been prepared and reported in excellent yields. Its antioxidant properties were examined. It exhibited good activity, which had the highest in vitro anti oxidant properties against DPPH scavenging activity. All these derivatives were characterized by melting point, Fourier-transformation infrared spectroscopy, Nuclear Magnetic Resonan (HNMR and 13C NMR).
A new class of potentially biologically active new 1,3,4-thiadiazol derivatives have been prepared and reported in excellent yields. Its antioxidant properties were examined. It exhibited good activity, which had the highest in vitro anti oxidant properties against DPPH scavenging activity. All these derivatives were characterized by melting point, Fourier-transformation infrared spectroscopy, Nuclear Magnetic Resonan (HNMR and 13C NMR).
Zone of inhibition of synthesized derivatives against Staphylococcus aureus
Zone of inhibition of synthesized derivatives against B. pumilus
The goal of this study was to develop, synthesise, and characterise a novel 1,3,5-trisubstituted-2-pyrazoline derivative, as well as test its antibacterial activity. The reaction of chalcone derivatives with succinic hydrazide in the presence of pyridine yielded the 1,3,5-tri-substituted-2-pyrazolines derivatives. The IR, 1HNMR, and mass spectral analyses were used to characterise a total of 20 substances. Antibacterial activity of the compounds was tested on five Gm+Ve bacterial strains (Staphylococcus aureus, S. Faecalis, Bacillus Substilis, P. Vulgaris, and B. Pumilus) and two Gm-Ve bacterial strains (Staphylococcus aureus, S. Faecalis, Bacillus Substilis, P. Vulgaris, and B. Pumilus) and two Gm-Ve i.e. Escherichia Coli, Klebsiella Penumoniae in two different concentration i.e. 50 and 100 µg/ml by Agar-diffusion method using Cup-plate method. Standard antimicrobial drugs were Norfloxacin and Ciprofloxacin. The antibacterial activity of substances against Gm+Ve bacterial strains (Staphylococcus Aureus, Staphylococcus Faecalis, Bacillus Substilis, Pseudomonas Vulgaris, and B. Pumilus) suggested the following order of action: BR-3 >BR-2>BR-1>CL-4>BR-4>CL-3> CL-2>CL-5>CL-6>ME-3>ME-2>ME-4>ME-5>ME-6>ME-7>CL-7>CL-8>CL-1>ME-8>ME-1>ME-8>ME-1>ME-8>ME-1>ME-8>ME-1>ME-8>ME-1>ME-8>ME-1>ME-8>ME-1>ME-8>ME-1>ME-8>ME-1>ME-8>ME The chemicals of the BR-1 to BR-4 series have the most action. ME-8, CL-8, CL-7, CL-1, ME-5, ME-6, and ME-1 have light activity, whereas CL-2, CL-5, ME-4, CL-6, ME-3, ME-2, and ME-7 have moderate activity. The compounds BR-3, BR-2, BR-1, CL-4, BR-4, and CL-3 have been shown to have excellent action. The result data of antibacterial activity suggested that Cl, Br, F, and Nitro substitution at third and Fifth position may enhance the antbacterial activity of the compounds but the methyl and methoxy substitution may resulted in reduction of the activity.
Zone of inhibition of synthesized derivatives against Staphylococcus aureus
The aim of the study was to develop, synthesis, and characterise a novel 1,3,5-trisubstituted-2-pyrazolines derivative, as well as to evaluate its antifungal activity. The reaction of chalcone derivatives with succinic hydrazide in the presence of pyridine yielded the 1,3,5-tri-substituted-2-pyrazolines derivatives. Total 20 compounds has been synthesized and characterized by the IR, 1HNMR and mass spectral analysis. Antifungal activity of the compounds carried out onfour fungal strains i.e. Saccharomyces cerevisiae, A. Niger, C. Albicans and R. Oryzae in two different concentration i.e. 50 and 100 µg/ml by Agar-diffusion method using Cup-plate method. The usual antifungal medicine was ketoconazole. All of the synthesized 1,3,5-trisubstituted pyrazole compounds (ME1-ME8, CL1-CL8, BR1-BR4) showed medium to best action against examined organisms, according to antifungal activity data. The antifungal activity of compounds against fungal strains (Saccharomyces cerevisiae, A. Niger, Candida albicans, and R. Oryzae) revealed the following order of action: CL-4 > BR-4 > CL-3 > CL-2 > ME-3> ME-2> CL-5 > CL-6 > ME-4 > ME-5 > ME-6 > ME-7 > CL-7 > CL-8>ME-8 >CL-1 >ME-1 > CL-5 > CL-6 > ME-4 > ME-5 > ME-6 > ME-7 > CL-7 > CL-8>ME-8 >CL-1 >ME-1. Electronegative groups (Br, Cl, F, and NO2) must be present at the third and fifth positions of the 1,3,5-pyrazoline ring for significant antifungal action. The presence of an electronegative group at the third and fifth positions may be required for the best action against bacterial and fungal strains, however the addition of F, NO2 has demonstrated moderate activity, while the substitution of methyl and methoxy groups may reduce the activity. The synthesized compounds in the BR-1 through BR-4 class are the most active.
1 Various isomers of triazine
1. 2,4,6 thichloro 1,3,5-triazine (cyanuric chloride)
Antibiotics are the class of drugs used for bacterial, viral & fungal infection. Antibiotic resistance is the ability of microorganism to withstand themselves against the effects of a drug. Every year antibiotic resistance causes more than 38000 deaths in Thailand, 23000 deaths in USA. In South Asia one new born child dies every 5 minutes from blood stream infection because antibiotics given are ineffective due to bacterial resistance. Now antibiotic resistance is a threat to global health. In this paper, triazene derivatives are kept in concern. Triazines are six-membered, nitrogen-containing heterocyclic scaffold with a wide range of pharmaceutical properties such as antibacterial, antifungal, anticancer, antioxidants, antitubercular, antimalarial and anti-inflammatory. Due to lack of new antibiotics as well older antibiotic are rapidly proving ineffective, derivatives of triazine would be of great significance in future prospective.
The method was published for determining microgram quantities of benzene 1,3,5-triol (phloroglucinol) in aqueous solution and some bulk samples using an easy, quick, and effective spectrophotometric method. The method uses a diazotization as well as coupling process in basic medium to produce a bright yellow water-soluble dye from Phloroglucinol and diazotized 4-Methoxy aniline That is stable and also has a maximum absorption wavelength of 420 nm. With a molar absorptivity of 1.5989x 104l mol-1 cm-1 as well as index of Sand ell sensitivity 0.001 2, Beer's law is followed across a concentration range of (2-40) of phloroglucinol.The ideal conditions for all color development are detailed, and even the suggested procedures for determining phloroglucinol in aqueous medium as well as some bulk sample have been successfully employed.
The objective of the paper was to design, synthesis and characterization of new 1,3,5-trisubstituted-2-pyrazolines derivative and evaluate for anti-inflammatory potential. The 1,3,5-tri-substituted-2-pyrazolines derivatives has been synthesized by the reaction of chalcone derivatives with 4-hydrazinylbenzene sulfonamide hydrochloride and phenyl hydrazine hydrochloride. Total Sixteen compounds has been synthesized and characterized by the IR, 1HNMR and mass spectral analysis. Proposed compounds have been evaluated for anti-inflammatory activity. Anti-inflammatory activity of the compounds carried out by two animal model i.e. Carrageenan induced, paw edema in rats and Inhibition of formalin induced paw edema in rats. Anti-inflammatory activity of the compounds C7, C8 and C2 were shown 98.26, 92.77 and 96.24 percentages of inhibition and compounds D7, D8 and D2 were shown 81.50, 83.81 and 78.32 percentages of inhibition as compared to the standard drug Diclofenac at 10 mg/kg was inhibit the inflammation 99.42 % after 6h. These result is a evident that synthesized compounds show relevant degree of anti-inflammatory activity as compared to the standard drug. It is also concluded that the presence of SO2NH2 group, Cl, CH3, OCH3 and N(CH3)2 group may provide the active compounds when attached to the pyrazoline group. But the addition of OH, Br and no substitution in phenyl ring may diminish the activity.
The goal of the study was to develop, synthesise, and characterise a novel 1,3,5-trisubstituted-2-pyrazolines derivative, as well as to assess its analgesic potential. The reaction of chalcone derivatives with 4-hydrazinylbenzene sulfonamide hydrochloride and phenyl hydrazine hydrochloride yielded 1,3,5-tri-substituted-2-pyrazolines derivatives. The IR, 1HNMR, and mass spectrum analyses were used to characterise a total of sixteen substances. Analgesic activity of the proposed substances has been tested. The analgesic effect of the produced compounds was tested using two methods: the hot plate test technique and acetic acid induced writhing in mice. To compare the effectiveness, pentazocine and acetyl acetic acid were utilised as reference drugs. The hot plate test technique and acetic acid induced writhing in mice were used to assess the analgesic effect of the 16 produced chemical series A1-A8, and B1-B8. The evaluation's outcomes were viewed using Pentazocine and acetyl acetic acid as the standard drugs. In a 90-minute hot plate test, compounds A2 (10.30 s), A4 (9.45 s), A7 (11.65 s), and A8 (11.26 s) showed a delay in paw withdrawal latency time. Compounds B2 (9.10 s) and B7 (10.42 s) prolong the paw withdrawal latency time after 90 minutes in series B1-B8, reduce the pain feeling, and inhibit pain induced by heat methods. Compounds A2, A5, A6, A7, and A8 from Series A1-A8 showed 83.00, 76.01, 80.34, 86.99, 88.15 percent inhibition, substantially (p0.05 and p0.001, respectively), and decreased the number of wriths caused by 0.6 percent acetic acid at a dosage of 10 mg/kg. Acetylsalicylic acid (10 mg/kg) appears to be more successful in lowering the number of wriths, with a 99.0% reduction in the number of wriths (p0.001). B1, B3, and B4 have the least amount of active activity. These all finding suggest that these synthesized compounds have the potential as analgesic agent.
Binding interactions of lofendazam with Cavity # 1 of 1KJT (A) Blue colour dotted lines indicate hydrophobic interactions with the residues TYR109A and LEU76A (B) Magenta colour dotted lines indicates Van der Waals interactions with the residues PHE77A, PHE78A, LEU76A, GLU112A, ASP111A, SER110A and TYR109A with cavity # 1 of Crystal structure of GABA-A receptor associated protein (1KJT). Compound 2
In the present investigation, some N1-benzoyl/ N1-(1,3,4-thiadiazol-2-yl amino acetyl) -7-substituted- 4-methyl-1,5-benzodiazepine-2-one were designed and docked at active site of cavity 1# of GABA-A receptor associated protein (1KJT) to distinguish from their hypothetical binding mode. The X-ray crystal structure of mammalian GABA-A receptor associated protein (1KJT) obtained from protein data bank was used as target protein. In this investigation the comparative analysis of the docking experiments of modelled compounds with known GABA agonist, Lofendazam was carried out. The dock scores calculated for Lofendazam was -4.7373. Among the modelled compounds, following conformation were found to have lower dock scores as indicated in bracket in comparison to other confermers; N1-benzoyl-7- bromo- 4-methyl-1,5-benzodiazepine-2-one, conformer_C3 (-5.0915), N1-(1,3,4-thiadiazol-2-yl amino acetyl) -7-chloro-4-methyl-1,5-benzodiazepine-2-one, Conformer_C2 (-4.6532). These conformers have more affinity for active site of GABA-A receptor associated protein than other molecules.
Formulation trails of Sil
Formulation of Sil-Que PLGA nanoparticles
Silymarin, a flavonolignan, derived from Silybum marianum, family Asteraceae has long been used as a hepatoprotective remedy. Silymarin has cytoprotective activities due to its antioxidant property and free radical scavenging activity. The pharmacokinetic studies of past three decades revealed that silymarin has poor absorption, rapid metabolism especially by Phase II metabolism and ultimately poor oral bioavailability. Quercetin, a flavonoid present in edible vegetables and fruits, It is a potent antioxidant and shows a wide range of biological functions. Quercetin improves blood levels and efficacy of number of drugs since it is P-Glycoprotein inhibitor and also inhibits drug metabolizing enzymes. Both silymarin and quercetin were, poorly soluble in the water shows low bioavailability. The advanced type of formulation like polymeric nanoparticles (PNPs) can be successfully utilised for bioavailability enhancement and targeting the Silymarin-quercetin to hepatocytes. A controlled release PNPs of silymarin-quercetin were prepared by spontaneous emulsification solvent diffusion (SESD) method using Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable polymer, D-alpha-tocopheryl poly (ethylene glycol) 1000 succinate (TPGS) used as a solubilizer, as an emulsifier. TPGS as an emulsifier and further as a matrix material blended with PLGA was used to enhance the encapsulation efficiency and improve the drug release profile of nanoparticles. Different formulations with various drug: polymer ratios and volume and concentration of surfactant, centrifugation time were evaluated. The effect of formulation parameters such as drug/polymer ratio, volume and surfactant content were evaluated. The surface morphology and size of the nanoparticles were studied by scanning electron microscopy (SEM) Transmission electron microscopy (TEM). Drug encapsulation efficiency and in vitro drug release profiles of nanoparticles were determined using UV spectrophotometry. The nanoparticles prepared with combination of both the drugs in this study were spherical with size range of 100–200 nm. It was shown that TPGS was a good emulsifier for producing nanoparticles of hydrophobic drugs and improving the encapsulation efficiency and drug loading and drug release profile of nanoparticles. Although the amount of the TPGS used had a significant effect on the nanoparticle size and morphology, the drug loading and release profile of nanoparticles
The COVID-19 pandemic has had a major impact on school children especially in their academic performance which may affect their mental health. The College students bear more pressure and have more serious physical and mental health problems. Due to the recent social changes in the education domain (e.g., the sharing of educational resources and advances in communication technology), the use of distance education is more and more, which changes the communication patterns between teachers and students, increases the isolation and independence of students, and thus becomes an important source of pressure for students [1]. Aim of the Study: To assess the level of stress during COVID-19 pandemic among the students of 10th and 12th standard. 2. To associate the level of stress during COVID-19 pandemic among the students of 10th and 12th standard with demographic variables. Methodology: An descriptive study will be use to assess the level of stress during COVID-19 pandemic among the 10th and 12th standard students in Wardha, Maharashtra. A purposive sampling technique will be use to pick the sample. A total 100 students who met the inclusion criteria will be select for this study. A Perceived Stress Scale was created to assess the stress. Expected Results: This study is mainly planned to assess the level of stress in students of 10th and 12th standard with the help of Perceived Stress Scale and demographic variables. Conclusion: Final conclusion will be drawn from final result of the statistical review.
Showing the clinical symptoms encountered in Orofacial Tuberculosis
Tuberculosis TB one of the major health problem in developed countries, with extremely high prevalence in Asian countries, mainly caused by "Mycobacterium Tuberculosis". Although pulmonary tuberculosis is the most common form of the disease, it also can occur in other organ systems such as lymph nodes, central nervous system, skeletal system, hepatic system, and gastrointestinal system, including the oral cavity. Extrapulmonary tuberculosis is an uncommon form of chronic infection that does not present typical signs and symptoms of pulmonary tuberculosis. Oral tuberculosis is an uncommon form and is often overlooked as it shows no path gnomic signs. This article presents our experience of unusual atypical tuberculosis in the Head and Neck region.
Background: Acinetobacter baumannii is typically short, rod shaped gram negative bacterium. The World Health Organisation has declared it as an opportunistic pathogen in humans. Multi drug resistance involves different genetic determinants making the pathogen difficult to treat. So this study is undertaken to characterize the 11 different drug resistant genes from 19 virulent strains of A. baumannii using in-silico PCR. Aim: Detect the 11 multidrug resistance genes among strains of A. baumannii by computational approach. Materials & Methods: 11 multidrug resistance genes of A. baumannii were selected. Forward and reverse primers of the 11 genes as reported from earlier studies were used for in-silico PCR amplification. 19 strains of A .baumannii set as default strains on the server were chosen and the amplicon bands were observed. Result: Among the 11 multidrug resistance genes only blaOXA-51like and blaADC were detected among the 19 virulent strains of A. bauamannii. Conclusion: The findings of the study documents the frequency of blaADC and blaOXA-51 like from the selected strains of A. baumannii. However further experimental validation must be done towards the periodical surveillance on the drug resistant strains of A. baumannii in hospital settings.
Comparison of frequency distribution and their status characteristics with variables of depression, anxiety and stress
Mean and standard deviation of trauma, depression, anxiety, and stress variables
Regression model between trauma caused by accidents and anxiety, depression and stress
Introduction: The efficacy of psychological and pharmacological approaches is broadly similar in the acute treatment of psychopharmacology disorders. One of the most important stressful environmental stimuli that can cause chronic stress is people's jobs. And since promoting the mental health of individuals in a society, especially its constituent classes, is essential to the dynamics and growth of that society, this research was conducted with the aim of investigating the relationship between trauma caused by accident and anxiety, depression, and stress in Kerman Emergency Medical and Emergency Center during 2019. Methods: This is a descriptive-correlational study. The statistical population was all 70 personnel members of Emergency Medical and 115 Emergency Centers in Kerman. The Depression, Stress and Anxiety Scale 21 and Trauma Screening were used as the instruments of measurement. Pearson and Spearman correlation coefficients through SPSS software were used to test the hypotheses. Results: There is a significant and direct correlation between trauma caused by accidents and personnel anxiety with a correlation coefficient of 0.407. Also, there is a significant and direct correlation between trauma caused by accidents and personnel depression with a correlation coefficient of 0.407. There is also a significant and direct relationship between trauma caused by accidents and personnel stress with a correlation coefficient of 0.388. Conclusion: Our data suggested that mental health along with personality traits is a solution to reduce stress and anxiety resulting from the personnel facing trauma caused by accidents.
Inhibition of (a) HT-29, (b) HCT-116 and (c) CT-26 by P. minus extracts for 3 days (except for acetone). Cell morphology of HT-29, HCT-116 and CT-26 were examined after being treated with IC 50 at (i) 0 hour, (ii) 24 hours (iii) 48 hours and (v) 72 hours. The photographs were taken at 10x magnification with inverted microscope (Nikon, Japan)
Determination of percentages extract yield (%) of different solvents of P. minus extracts
Aims: To investigate the cytotoxic properties of different polarity solvents of Polygonum minus extracts towards colon cancer cell lines, HT-29, HCT-116 and CT-26. Study Design: Experimental study. Place and Duration of Study: Central Laboratory, Tissue Culture Laboratory, Universiti Sultan Zainal Abidin, Terengganu between September 2019 until December 2019. Methodology: The different polarity solvents of P. minus extracts had been led to tetrazolium salt reduction (MTT) assay and an inhibition concentration of 50 (IC50) value for their cytotoxic potential against colon cancer cells. Then, cell morphology observation and fluorescence double staining of treatment cells were determined using a light inverted microscope and acridine orange/propidium iodide staining. Results: The results indicated that an extraction yields aligned from 0.01% for acetone and ethyl acetate to 0.45% for aqueous solution with decreasing order of aqueous solution > 70% aqueous ethanol > 50% aqueous ethanol > methanol > ethanol > acetone and ethyl acetate. Meanwhile, the ethyl acetate extract showed a higher cytotoxic effect at IC50 values of 7.00 ± 0.06 µg/mL and 7.00 ± 0.30 µg/mL towards the HCT-116 and CT-26 cells; and 50% aqueous ethanol towards HT-29 cells (24.00 ± 0.01 µg/mL). The different solvent extracts of P. minus induced cytotoxic effects on the treated cell lines by altering their normal cell morphology and cell membrane integrity (except for acetone extract). Conclusion: Therefore, the use of different polarity solvent extracts of P. minus as an anti-cancer agent is promising more on ethyl acetate and warrants further investigation.
Extraction yield of singgang extracts using 100% EtOH, 70% EtOH, 50% EtOH and distilled water
Aim: To investigate anti-proliferative effect of three types of Terengganu singgang extracts on colon cancer cell lines (HT-29, HCT-116, CT-26). Study Design: Experimental study. Place and Duration of Study: Central Laboratory, Tissue Culture Laboratory, Universiti Sultan Zainal Abidin, Terengganu between April 2019 and July 2019. Methodology: Samples comprised three types of singgang dish, which were prepared, cooked, and then extracted with distilled water and ethanol (EtOH) in different strengths, 50%, 70%, and 100%.These singgang samples were chub mackerel (ST), Indian mackerel (SK),and a control sample with no fish (SC). Extracts were analyzed for their anti-proliferative effect by MTT-based assay. Then, the morphological of cell apoptotic changes was observed using light inverted microscope. Results: Experimental assays showed that the SC sample extracted in 100% EtOH produced the highest yield (3.7%).The extract of ST in aqueous (0.27 (0.11)) yielded the most cytotoxic value, followed by extract SK in 100% EtOH (0.28 (0.10)) and extract SC in 50% EtOH (0.20 (0.08)). Then, the anti-proliferative effect was confirmed with morphological changes of cell which were characterized by cell shrinkage, membrane blebbing, and fragmentation of apoptotic bodies after 24, 48 and 72 hours of treatment. Conclusion: In conclusion, the ST extract showed the best anti-proliferative effect.
Aim: Anethum sowa L. isan aromatic plant with pharmacological potential. The chemical composition and the therapeutic of Anethum sowa L. herb oil grown in South Karnataka is very few; moreover, its essential oil and extract together is not being studied and compared for its effects on colon cancer cell lines HCT -116 and anti collagense study . Methods: The current investigation was intended to sight see the incidence of components present in the herb oil examined by (GC-MS), antioxidant , antimicrobial , anticancer & anticollagenase potential was investigated and further the insilco docking studies to unleash the potential drug like molecules in the therapeutic plant was studied . Results: 5-Oxo-4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]pyridine-3-propionic acid methyl ester, (17.41%),beta-Amyrin(8.20),ritodrine(6.49),1-Naphthalenol,decahydro-1,4a-dimethyl-7-(methylethylidene)-,[1R-(1.alpha.4a.beta,8a.alpha)](2.39%),meta-Cymene(1.95%),trans-z-alpha-Bisabolene epoxide (1.80), and Viridiflorol(0.77%) were the new compounds isolated from this therapeutic plant, and Anethum sowa L. herb ethanolic extract contained many potential phytochemicals. The total phenol and flavonoid of the herb extract were 0.136mg/ml. and 0.108mg/ml respectively . Anethum sowa L. herb extract ABTS antioxidant assay showed excellent activity with an IC50 of 540µg/ml which was in power with gallic acid which showed an IC 50 of 393µg/ml. Essential oil of Anethum sowa L. herb exhibited potent antimicrobial activity against all the three microorganisms E-coli strain (MTCC 433), Klebsiella pneumoniae strain (MTCC 3384) Streptococcusmutants strain (MTCC 497) with a minimum inhibitory concentration of 20% herb oil . Cytotoxicity of Anethum sowa L.herb essential oil and ethanolic extract against Colon cancer cell lines – HCT -116 , showed that herb oil and herb ethanolic extract repressed the cell growth of the cell . Herb oil with an IC50 79.75µg/ml was more effective than the herb extract . Herb essential oil showed the maximum capacity in inhibiting the collagenase when compared to ethanolic extract of herb, the percentage of inhibition of Anethum sowa L. herb essential oil was found to be 60.89% and that of herb extract was (15.18%). Conclusion: Herb oil showed very good anticancer, antimicrobial and anticollagenase activity and by the In silico docking performed between the compounds present in the herb oil, MAI-150 and APC of Homo sapiens, it was found that lupeol showed the highest binding affinity with APC when compared with MAI-150 and rest other compounds present in the herb oil.
Balanites aegyptiaca (L.) Delile (Zygophyllaceae), is used in traditional medicine for the treatment of intestinal worms, wounds, and inflammatory diseases. The purpose of this study is to assess the anti-proliferative effect and to analyse the pro-apoptotic and cell cycle arrest activities of B. aegyptiaca root bark extract and fractions against colorectal cancer cells HCT-116 and HT-29. The cytotoxicity of the crude extract and fractions were evaluated by MTS assay. The most active fractionwas subjected to crystal violet assay, Hoechst staining, cell cycle arrest, and annexin V/PI assays on cancer cells to highlight its mechanisms of action. The ethyl acetate fraction demonstrated the most cytotoxic effect on HCT-116 and HT-29 with IC50 values ranging between 3 and 4 µg/mL. At 10 µg/mL in the cell cycle arrest assay, the fraction increased G1 phase by 3.83% on HCT-116 and by 8.6% on HT-29 whilst G2/M phase was decreased by 5.63% on HCT-116 and by 6.62% on HT-29. Moreover, apoptotic cells were increased by 11.4% on HCT-116. The results suggest a potential source of anticancer molecules against colorectal cancer for isolation from the ethyl acetate fraction.
MIR-124-1 is a brain-abundant MIRNA, whose expression is important for neuronal tissue division, growth and actions. However, expression of miR-124-1 regulatory mechanisms controlling its actions in neuronal cells in health and diseases still poorly addressed. To understand mechanism for transcriptional and functional regulation of miR-124 in neuronal and glioblastoma cells, this study combined gene expression profiling data and computational transcription factor and microRNA target predictions. The present research focuses on transcription factors and DNA methylation, which are central to miR-124-1 expression regulation. A core promoter sequence of miR-124-1 was predicted to be 500 bp and 100 bp, upstream and downstream of its transcription start sites. Seventy three binding sites of fifty transcription factors in promoter region were found, using MatInspector software. Among these transcription factors, MEIS1, POU3F2, SALL2, ETV1, and MAZ, are known to be brain-enriched transcriptional activators. By using omics data analysis, expression of MAZ, PLAG1 KLF2 as well as a transcriptional repressor ZNF239 showed significant correlation with decline in miR-124-1 expression in glioblastoma cells. Furthermore, a potential CpG island was reported in the promoter, providing another mechanism for transcriptional inhibition of miR-124. As miR-124-1 regulates a number of neuronal physiological and pathological processes, we made an attempt to define its potential targets. A computational prediction of miR-124-1 targets suggested 265 targets with two or more conserved seed sites. Pathway-based analysis of these target genes revealed a significant enrichment for axonal guidance and cancer signaling pathways. At least ten of these targets, SRGAP1, GNAI3, PLXNA3, SEMA5A, SEMA6A, CEBPA, CBL, RASSF5, MITF, and RPS6KB1, showed expected inverse correlation between their expression values and miR-124-1 suppression in glioblastoma cells. Taken together, our data form foundation of subsequent future validation researches for miR-124-1 expression regulation including transcription factors and CpG Island within its promoter as well as functional regulation comprising biological pathways controlled by its target genes.
Introduction: Pulpitis is a debilitating inflammation of the pulp of the tooth. Bacteria infiltrate the pulp of the tooth, causing it to swell. It may affect one or more teeth. Pulpitis comes in two varieties - acute and chronic. Chronic pulpitis is a long-term inflammation of the pulp tissue that results in permanent damage to the reliability of the pulp tissue. Aim: To assess the prevalence of chronic pulpitis among 13 to 17 year old pediatric patients visiting the private dental institution in Chennai. Materials and Methods: Case sheets of patients were obtained from Record management system software for analysis. Patients with chronic pulpitis within the age group 13 to 17 were selected and the sample size was found to be n = 165 patients. The collected data was then tabulated for statistical analysis using SPSS. Results: From the results obtained in our study , chronic pulpitis was most prevalent in females with age of 16 particularly in mandibular molars (16.97% in 36 and 13.94% in 46). Conclusion: Within the limitations of the study it can be concluded that mandibular molars were commonly affected due to chronic pulpitis and by knowing the prevalence and pathophysiology of chronic pulpitis, dental clinicians can prevent the progression of this condition.
Aims: Polyketide synthase 13 (Pks13) is an essential enzyme in the synthesis of mycolic acids biosynthesis pathway of Mycobacterium tuberculosis (Mtb). Therefore, Pks13 is a promising drug target for tuberculosis treatment. Here we report the in silico design and evaluation of novel Pks13 inhibitors made of benzofuran derivatives with favorable predicted pharmacokinetic profiles. Methodology: A 3D model of Pks13-TAMx complexes was prepared for a training set of 18 TAMs with experimentally determined inhibitory potencies (half-maximal inhibitory concentrations ) by using in situ modifications of the crystal structure of the TAM1-Pks13 complex (PDB entry 5V3X). A linear QSAR model was built, correlating computed gas phase enthalpies of formation ( ) of Pks13-TAMx complexes with the in order to find active conformations of the 18 TAMs. Furthermore, taking into account the implicit solvent effect and entropy changes upon ligand binding, a superior QSAR model was brought forth, correlating computed complexation of Gibbs’ free energies . Using the active conformations of the training set TAMs, we built a pharmacophore model (PH4) which was used to virtually screen novel analogs included in a virtual combinatorial library (VCL) of compounds containing benzofuran scaffolds. The PH4 model screened the VCL, which was formerly filtered by Lipinski’s rule-of-five, in order to identify new benzofuran analogs. Results: Gas phase QSAR model: , ; superior aqueous phase QSAR model , and PH4 pharmacophore model: , . The PH4-based screening retained 109 new TAM analogues. Finally, the predicted pharmacokinetic profiles of these new analogues were compared to current orally administered antituberculosis drugs, and the former were found to be almost 92 times more active than TAM2 ( . Conclusion: This computational approach, which combines molecular mechanics and the Poisson–Boltzmann (PB) implicit solvation theory, the pharmacophore model, the analysis of Pks13-TAMs interaction energies, the in silico screening of VCL compounds, and the inference of ADME properties resulted in a set of new suggested Pks13 inhibitors.
Aims: To observe outcomes in patients admitted to the High Dependency Unit (HDU) at the Field Isolation Centre Karachi after 14 days of COVID-19 treatment protocol. Patients and meth­ods: This cross-sectional study was conducted at HDU/FIC Karachi at Expo Centre. The duration of the study was from 1st December 2020 to 10th March 2021. All patients diagnosed as cases of COVID-19, of both genders with age ranging from 18 to 91 years were included. Methodology: All patients were treated according to the protocols set as under: Anti-viral drug Remdesivir was given in all patients aged less than 75 years, with moderate to severe disease (based on clinical classification released by National Health Commission of China). Dexamethasone 6mg IV once daily was initiated in all oxygen dependent patients and increased to twice daily if Ferritin levels were greater than 1000ug/L. As a supportive treatment, patients with moderate or severe disease were given Injection Enoxaparin in prophylactic dose and in therapeutic dose for patients with elevated D-Dimer levels. Along with this, superadded bacterial infections were covered with broad-spectrum antibiotics and adjusted as per culture and sensitivity. Patients were also given Famotidine (H-2 receptor blocker), and anti-hyperlipidemic drug Fenofibrate based on initial supportive literature. But in patients with known liver diseases or with deranged ALT levels ≥ 5 times upper limits of normal, Fenofibrate and Remdesivir were discontinued. All data regarding the medications given, oxygen demand, disease severity and co-morbid conditions and the outcome on 14th day of admission was collected through the online HMIS database and patient files, on pre-approved Performa. Patients’ confidentiality was ensured. Results: A total of 183 patients were included in the study. There were 66.7% male and 33.3% female patients with a mean age 59.01±14.83 years. Majority (72.1%) of patients were of more than 50 years of age. Among 183 patients, 2.2% were smokers, 51.9% were hypertensive and 41% were diabetic while 5.5% had ischemic heart disease, and 3.8% were found with asthma. We found 84.7% with shortness of breath, 67.8% of patients with fever, 57.9% with cough, 17.5% with myalgia, 14.8% with fatigue, 4.9% with diarrhea, 2.7% with nausea and 1.6% with vomiting. In our study, 35% of patients expired. Out of 183 patients, 147 patients needed oxygen at the time of admission, which was reduced to 45 patients after 2 weeks, while 26 patients need NIV at admission, reduced to 21 patients on NIV after 2 weeks. We found significant mean difference of age (p=0.000) while significant association of outcome was found with Remdesivir given (p=0.039), cough (p=0.025), intubation after 2 weeks (p=0.006), Oxygen need at admission (p=0.000), Oxygen need after 2 weeks (p=0.000), NIV Need at admission (p=0.000) and NIV Need after 2 weeks (p=0.000). Conclusion: This study revealed various characteristics (age, supplemental oxygen requirement and comorbid conditions) of COVID-19 patients to be associated with poor outcome at 14th day of admission. Remdesivir was found to decrease mortality, especially in patients with moderate to severe disease.
Aim: A major challenge in the development of new antibiotics is the biocompatibility within biological environment. Ionic complementary peptide (EAK-16) from amyloid protein, have the ability to adopt secondary structure conformation at membrane interfaces. This study aimed to investigate the effect of membrane on EAK-16 peptide folding and their antibacterial applications. Methodology: We studied secondary structural conformation of EAK-16 using circular dichroism (CD) spectroscopy in an aqueous environment and at membrane bilayers interfaces. Initially, the antibacterial efficacy was investigated against both Gram-positive and Gram-negative bacteria. Membrane mimicking models were synthesised with dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylserine (DMPS) lipid vesicles using calcein leakage assay. Results: EAK-16 showed transition in secondary structural conformation. In aqueous environment, it was predominantly β-sheets and at membrane interfaces, it was mainly α-helical. EAK-16 peptide was highly active against bacteria (at minimum concentration applied) and membrane leakage was found to be > 60%. This effect was confirmed with both anionic lipids (DMPS) and neutral lipids (DMPC). The helical transition of EAK-16 could be a major factor to disrupt the membrane and bacterial death Conclusion: The secondary structural conformation and calcein leakage data suggest that EAK-16 has potential to kill bacteria by adopting helical tilted conformation and membrane perturbation via lysis. This study revealed structure-function relationship of peptide and lipid bilayers to further investigate the mode of pore formation and mode of action of EAK-16 in membrane perturbation and antibacterial efficacy.
The estimated prevalence of HPV16/18 in cervical cancer
The comparative HPV distribution in different zones of India
There is high incidence of cervical cancer in Bihar, India. Vaccination for cervical cancer in developed countries has played a crucial role in limiting the incidence rate of cervical cancer worldwide. In consideration of debate on clinical efficacy of Human Papilloma Virus (HPV) vaccine in India, study on the prevalence of high risk HPV 16/18 strains in different regions of the nation becomes very crucial. Few individual states have started vaccination but centralised vaccination program does not exist due to lack of sufficient genotypic study of Human Papilloma Virus in different parts of India. Bihar is the third most populous state of India and HPV 16/18 distribution has not been reported yet. The nationwide data of HPV 16/18will help to develop a unified centralised vaccination program. We carried out a distribution study of high risk HPV type 16 and 18 in cervical cancer patients attending a tertiary care hospital of Bihar, India.HPV 16/18 types were analysed in cervical cancer tissues (n = 96) of patients attending the regional cancer hospital of Bihar. Tissue samples were analysed for HPV 16 and HPV 18 using a Real Time PCR technique. The results suggest very high prevalence of HPV 16/18. HPV was identified in all the samples (96/96). About, 74 (77.08%) samples presented with HPV 16 whereas, 16 (16.67%) of the samples presented with HPV 18. 6 Co-infection was presented in 6 (6.25%) of the samples of cervical cancer tissues. HPV 16/18 prevalence is more in the women aged between 41 to 61 years.We report 100% prevalence of HPV16/18 in the cervical cancer tissue samples. A way to minimise this gynaecological concern would be to introduce prophylactic vaccines and early screening in the state of Bihar. The data generated would be crucial in drafting for community screening of HPV. We strongly emphasize the prophylactic HPV Vaccination against HPV 16 to control the alarming rate of cervical cancer in one of the most populous state of India, Bihar.
Background and Objectives: Early Childhood Caries is considered as a common chronic disease in children. Since some research had concluded that children with higher levels of Streptococcus mutans are associated with a higher incidence of decayed, missing, and filled teeth, the present study was undertaken to analyze the salivary Streptococcus mutans of children with different caries status using species specific 16S rRNA gene sequencing technology to evaluate the quantity of Streptococcus mutans with respect to different caries status. Materials and Methods: Children between 3-6 years were selected and divided into 3 groups, Group I- Caries free, Group II-Early Childhood caries and Group III- Severe Early childhood caries. The caries status was assessed using dmfs and the severity of caries was assessed using pufa index. Salivary samples were collected to isolate DNA and Real time PCR was done with 16SrRNA primer specific to Streptococcus mutans to estimate the quantity of Streptococcus mutans in children with different caries status. Results: There was a significant difference in the mean CT values among the study groups (p < 0.001). Post hoc Tukey test revealed that, Group I had a significantly higher mean CT values than that of Groups II and III. Pearson's correlation analysis was carried out to correlate dmfs value with CT values and to correlate the pufa value with the fold change. There was a negative correlation between dmfs score and CT values and positive correlation between pufa score and fold change. Conclusion: There was a higher expression of 16SrRNA gene in Severe Early childhood caries group, followed by Early childhood caries and caries free group, indicating a high level of Streptococcus mutans in Severe Early childhood caries group and there was a negative correlation between dmfs score and CT values and a positive correlation between pufa score and fold change.
Introduction: Congenitally missing teeth or hypodontia is a condition where some of the adult teeth fail to develop. There have been theories involving genetic and environmental factors which lead to prevalence of permanent missing teeth. Missing teeth can affect the patients and cause many other problems such as malocclusion, periodontal damage, delay in bone growth, reduced mastication and unfavourable skeletal appearance. Thus having awareness about missing teeth and the eruption sequence dentists will be able to identify the missing teeth and correct the same. Aim: The aim of this study is to analyse the prevalence of missing in the paediatric population between 8-17 years of age. Materials and Methods: The data for the study n=4453 patients was collected by analysing the case sheets of patients who visited Saveetha Dental college from June 2019- February 2021.The collected data was analysed and subjected to statistical analysis using the SPSS software by IBM of version 23. Results: From the results of the study, missing teeth in the 8 to 10 age group was highest in the second quadrant at 27.27% with most common missing teeth being left maxillary lateral incisor 15.76%, in the 11-13 age group it was highest in the third quadrant at 32.39% with most common missing teeth being left mandibular lateral incisor 16.37% and in the 14 -17 age group it was highest in first quadrant at 40.87% with the most common missing teeth being right maxillary first premolar 15.08%. It is also observed that the most common cause of missing teeth in 8-10 age group is due to congenital absence at16.46%, in 11-13 age group due to trauma at 16.46% and in 14-17 age group due to caries at 18.90%. Conclusion: Missing teeth is a very common dental anomaly encountered these days. From the present study it can be concluded that the most common cause of missing teeth was congenital absence of it. Larger community based studies should be conducted to estimate more precisely the causes for missing teeth. They are very important to be analysed so that they can prevent complications that can occur. In our study missing teeth is being analysed at an earlier age group of 8-17 reducing the chances of future complications.
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Nisha Adhikari
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Dirgha Raj Joshi
  • Istituto Superiore di Sanità
Davoud Balarak
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Emmanuel Ifeanyi Obeagu
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Povetkin Sergey Nikolaevich
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