Publications by authors named "Kaleem Ullah"

39 Publications

Frequency and Outcome of Hepatic Arterial Thrombosis in Recipients of Living Donor Liver Transplantation.

J Coll Physicians Surg Pak 2021 Aug;31(8):897-902

Department of Liver Transplant, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat, Sindh, Pakistan.

ABASTRACT Objective: To determine the frequency, risk factors, and management of hepatic arterial thrombosis (HAT) in recipients of living donor living transplantation.

Study Design: Cohort study.

Place And Duration Of Study: Department of Liver Transplant, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat, Sindh, Pakistan, from 1st January 2019 to 31st July 2020.

Methodology: Two hundred and forty living donor liver transplants (LDLT) recipients' data were evaluated. Frequencies of HAT were recorded, and various risk factors for the development of HAT were analysed by comparing HAT group (n = 12) and non-HAT group (n = 228). Management and outcome of HAT cases were also reviewed. Statistical analysis of this study was done with SPSS software version 21.

Results: Out of 240 patients, 212 (88.3%) were males. Overall mean age was 39.40 ± 12.14 years. Mean model for end-stage liver disease (MELD) score was 18.70 ± 4.98. Overall male to female ratio was 7.5:1. The common indication for LDLT in these patients was chronic liver disease secondary to hepatitis B and C virus infection in 85% of patients. Postoperative HAT incidence was found as 5%.  Risk factor found statistically significant was intraoperative platelet transfusion.

Conclusion: HAT is a deadly complication and needs early detection to avoid graft loss. The risk factor documented in this study should be avoided, if possible. Moreover, prompt and quick action is necessary for re-vascularisation to avoid re-transplantation. Key Words: Living donor, Hepatic arterial thrombosis, Liver transplantation.
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http://dx.doi.org/10.29271/jcpsp.2021.08.897DOI Listing
August 2021

Primary biliary cirrhosis in early childhood - A rare case report.

Int J Surg Case Rep 2021 Jul 18;85:106215. Epub 2021 Jul 18.

Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat, Sindh, Pakistan.

Introduction And Importance: Primary biliary cirrhosis (PBC) is a chronic and progressive autoimmune liver disease with no known etiology. This disease is mainly characterized by granulomatous destruction of intrahepatic biliary ducts, severe peri-portal inflammation, and ultimate progress to liver fibrosis and cirrhosis. Here, we report a five-year-old girl diagnosed with PBC, presented to us with end-stage liver disease for liver transplantation. Our patient successfully underwent liver transplantation with an uneventful recovery. This case highlights the need for awareness to report further PBC cases in the pediatric age group.

Case Presentation: A five-year old female child presented with a 6 months history of progressive jaundice. She had multiple admissions for hepatic encephalopathy and this time she was admitted for hepatic transplantation. On examination, she was icteric and had hepatomegaly. After thorough workup, she underwent successful hepatic transplantation and was alright post-operatively. At 6 months follow up, she is doing well.

Conclusion: PBC is rare in childhood. The natural history and exact incidence of PBC in childhood are not known. Hence, there is a need for awareness to report further PBC cases in the pediatric age group.
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http://dx.doi.org/10.1016/j.ijscr.2021.106215DOI Listing
July 2021

Synthesis, Characterization and Safety Evaluation of Sericin-Based Hydrogels for Controlled Delivery of Acyclovir.

Pharmaceuticals (Basel) 2021 Mar 8;14(3). Epub 2021 Mar 8.

College of Pharmacy and Health Sciences, Ajman University, P.O. Box 346, Ajman, United Arab Emirates.

Conventional formulations of antiviral drug acyclovir have various limitations such as low bioavailability. The current study was aimed at developing polymeric matrices for the controlled delivery of acyclovir using sericin as polymer and acrylic acid (AA) as a monomer. The free radical polymerization technique was used for hydrogel formulation. Briefly, sericin was chemically cross-linked with acrylic acid. '-'-methylene bis-acrylamide (MBA) and ammonium persulfate (APS) were used as cross-linker and initiator, respectively. FTIR spectra showed that acyclovir was successfully loaded into sericin hydrogel. SEM micrographs revealed that the outer surface was solid-like and smooth. According to DSC thermograms, the developed polymeric network was thermally stable. Amorphous nature of acyclovir was observed in XRD. The pH of medium and reactants' concentration affected swelling dynamics and acyclovir release pattern. In addition, drug release occurred through a diffusion-controlled process. Sericin hydrogel suspension was well tolerable up to 3800 mg/kg of rabbits' body weight. Haematology and serum chemistry results were well within the range signifying normal liver and kidney functions. Similarly, histopathology slides of the rabbit's vital organs were also in normal condition without causing any histopathological change. It was concluded from the findings that sericin-co-AA polymeric matrices are ideal for the pH-dependent delivery of acyclovir.
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http://dx.doi.org/10.3390/ph14030234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000570PMC
March 2021

Biosynthesis of Polyhydroxyalkanoates (PHAs) by the Valorization of Biomass and Synthetic Waste.

Molecules 2020 Nov 26;25(23). Epub 2020 Nov 26.

Department of Zoology, University of Gujrat, Gujrat 50700, Pakistan.

Synthetic pollutants are a looming threat to the entire ecosystem, including wildlife, the environment, and human health. Polyhydroxyalkanoates (PHAs) are natural biodegradable microbial polymers with a promising potential to replace synthetic plastics. This research is focused on devising a sustainable approach to produce PHAs by a new microbial strain using untreated synthetic plastics and lignocellulosic biomass. For experiments, 47 soil samples and 18 effluent samples were collected from various areas of Punjab, Pakistan. The samples were primarily screened for PHA detection on agar medium containing Nile blue A stain. The PHA positive bacterial isolates showed prominent orange-yellow fluorescence on irradiation with UV light. They were further screened for PHA estimation by submerged fermentation in the culture broth. Bacterial isolate 16a produced maximum PHA and was identified by 16S rRNA sequencing. It was identified as HA-16 (MN240936), reported first time for PHA production. Basic fermentation parameters, such as incubation time, temperature, and pH were optimized for PHA production. Wood chips, cardboard cutouts, plastic bottle cutouts, shredded polystyrene cups, and plastic bags were optimized as alternative sustainable carbon sources for the production of PHAs. A vital finding of this study was the yield obtained by using plastic bags, i.e., 68.24 ± 0.27%. The effective use of plastic and lignocellulosic waste in the cultivation medium for the microbial production of PHA by a novel bacterial strain is discussed in the current study.
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http://dx.doi.org/10.3390/molecules25235539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728366PMC
November 2020

Pharmacokinetic Profile of Oxaliplatin-Loaded pH-Responsive Hydrogels in Rabbits.

Curr Pharm Des 2020 ;26(44):5755-5763

Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Pakistan.

Background: Oxaliplatin (OXP), a 3rd generation platinum compound, which causes severe side effects due to; impulse high concentration in the bloodstream thereby exposing healthy cells at a high ratio, nonspecific delivery at the target site and non-compliance is administered intravenously.

Objective: The project was aimed at the development, characterization, and in-vitro and in-vivo evaluation of pHresponsive hydrogels for oral administration of OXP.

Methods: Hydrogel formulations were synthesized through a free radical polymerization technique followed by brief characterization using various techniques. The hydrogels were investigated for various in-vitro studies such as sol-gel, drug loading, swelling, drug release, and MTT-assay. While in-vivo studies such as oral tolerability, histopathology, and hematology studies were performed on rabbits. A simple and sensitive HPLC-UV method was optimized and the comparative pharmacokinetic study was performed in rabbits using OXP-oral solution and OXP-loaded hydrogels.

Results: In-vitro characterization confirmed that the reactant was successfully crosslinked to form thermally stable hydrogels with decreased crystallinity and rough surface. Swelling and drug release showed that hydrogels were more responsive to basic pH (6.8 and 7.4) in comparison with pH 1.2. The blank hydrogels were cytocompatible as more than 95% of the cells were viable while free OXP and OXP-loaded hydrogels displayed dosedependent cytotoxic effect. In-vivo studies confirmed that chitosan and gelatin hydrogel suspension was well tolerable up to 3800 mg/kg and 4000 mg/kg of body weight, respectively. Hematology and serum chemistry reports were well within the range suggesting normal liver and kidney functions. Similarly, histopathology slides of rabbit vital organs were also found normal without causing any histopathological change.

Conclusion: HPLC-UV method was successfully optimized for OXP detection in oral solution and hydrogels administered to rabbits. A significant difference was found among various pharmacokinetic parameters by comparing the two groups including half-life (t), t, C, AUC MRT, V, and L.
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http://dx.doi.org/10.2174/1381612826666200813125159DOI Listing
April 2021

Comparing Ripasa Score And Alvarado Score In An Accurate Diagnosis Of Acute Appendicitis.

J Ayub Med Coll Abbottabad 2020 Jan- Mar;32(1):38-41

Surgery Department, Khyber Teaching Hospital, Peshawar.

Background: The clinical diagnosis of acute appendicitis remains difficult despite the use of different scoring systems. A high rate of negative appendectomies is no longer acceptable. This study was aimed to compare RIPASA score and Alvarado score in Pakistani population for the diagnosis of acute appendicitis using histopathology as a gold standard.

Methods: This crosssectional prospective study was carried out from January to September 2018 in the Accident and Emergency Department and Department of Surgery, Khyber Teaching Hospital, Peshawar. Patients clinically suspected as acute appendicitis aided by routine ultrasound were included in the study. RIPASA and Alvarado scoring were done in all patients. After appendectomies, specimen was sent for histopathological examination. A score of 7.5 was considered as optimal cutoff threshold for RIPASA and 7 for Alvarado score. Sensitivity, Specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and accuracies of both scores were calculated.

Results: A total of 300 patients were included in the study. The mean age of patients was 28±10.0 years and there were 176 males. Sensitivity, Specificity of RIPASA score and Alvarado score was found to be 98.52% and 90%, and 68.15% and 80% respectively. Positive Predictive Value and NPV of RIPASA score was 98.88% and 97.67% as compared to 96.84% and 21.82% for Alvarado score. Diagnostic accuracy of RIPASA and Alvarado score was 97.67% and 69.33% respectively..

Conclusions: RIPASA scoring system is a more accurate, sensitive and specific indicator of diagnosing acute appendicitis as compared to Alvarado scoring system.
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November 2020

Synergistic Neuroprotective Effect of Endogenously-Produced Hydroxytyrosol and Synaptic Vesicle Proteins on Pheochromocytoma Cell Line Against Salsolinol.

Molecules 2020 Apr 8;25(7). Epub 2020 Apr 8.

Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, School of Life Science, Beijing Institute of Technology, Beijing 100081, China.

Oxidative stress triggers a lethal cascade, leading to Parkinson's disease by causing degeneration of dopaminergic neurons. In this study, eight antioxidants were screened for their neuroprotective effect on PC12 cells (pheochromocytoma cell line) under oxidative stress induced by salsolinol (OSibS). Hydroxytyrosol was found to be the strongest neuroprotective agent; it improved viability of PC12 cells by up to 81.69% under OSibS. Afterward, two synaptic vesicle proteins, synapsin-1 and septin-5, were screened for their neuroprotective role; the overexpression of synapsin-1 and the downregulation of septin-5 separately improved the viability of PC12 cells by up to 71.17% and 67.00%, respectively, compared to PC12 cells only treated with salsolinol (PoTwS) under OSibS. Subsequently, the PC12+syn+sep cell line was constructed and pretreated with 100 µM hydroxytyrosol, which improved its cell viability by up to 99.03% and led to 14.71- and 6.37-fold reductions in the levels of MDA and HO, respectively, and 6.8-, 12.97-, 10.57-, and 7.57-fold increases in the activity of catalase, glutathione reductase, superoxide dismutase, and glutathione peroxidase, respectively, compared to PoTwS under OSibS. Finally, alcohol dehydrogenase-6 from was expressed in PC12+syn+sep cells to convert 3,4-dihydroxyphenylacetaldehyde (an endogenous neurotoxin) into hydroxytyrosol. The PC12+syn+sep+ADH6 cell line also led to 22.38- and 12.33-fold decreases in the production of MDA and HO, respectively, and 7.15-, 13.93-, 12.08-, and 8.11-fold improvements in the activity of catalase, glutathione reductase, superoxide dismutase, and glutathione peroxidase, respectively, compared to PoTwS under OSibS. Herein, we report the endogenous production of a powerful antioxidant, hydroxytyrosol, from 3,4-dihydroxyphenylacetaldehyde, and evaluate its synergistic neuroprotective effect, along with synapsin-1 and septin-5, on PC12 cells under OSibS.
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http://dx.doi.org/10.3390/molecules25071715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181248PMC
April 2020

Morgagni-Larrey Hernia: A Possible Cause of Recurrent Lower Respiratory Tract Infections.

Cureus 2019 Feb 7;11(2):e4035. Epub 2019 Feb 7.

Thoracic Surgery, Nishtar Medical University Hospital, Multan, PAK.

Morgagni-Larrey hernia is an exceedingly rare presentation of congenital diaphragmatic hernia. Despite its rarity, it is associated with significant risk of morbidity and mortality. Herein, we describe a unique case report of an elderly woman who presented with left-sided chest pain, dyspnea, and chronic history of recurrent respiratory tract infections. On the basis of her medical history, general physical examination and imaging studies, she was operated for a presumptive diagnosis of thymolipoma. However, the intra-operative findings revealed that it was an unusual variant of a diaphragmatic hernia and the hernia sac appeared through the retrosternal foramen of Morgagni. Hence we concluded that it was a Morgagni-Larrey hernia compressing the lungs and heart. Consequently, the hernia was reduced and the defect was repaired. During the postoperative period, the patient had an uneventful recovery. To conclude, the possibility of a Morgagni-Larrey hernia should be strongly considered while evaluating a patient with recurrent chest infections, dyspnea, and vague chest pain.
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http://dx.doi.org/10.7759/cureus.4035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053801PMC
February 2019

Self-Redirection of Metabolic Flux Toward Squalene and Ethanol Pathways by Engineered Yeast.

Metabolites 2020 Feb 1;10(2). Epub 2020 Feb 1.

Institute for Synthetic Biosystem, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China.

We have previously reported that squalene overproducing yeast self-downregulate the expression of the ethanol pathway (non-essential pathway) to divert the metabolic flux to the squalene pathway. In this study, the effect of co-production of squalene and ethanol on other non-essential pathways (fusel alcohol pathway, FA) of was evaluated. However, before that, 13 constitutive promoters, like and were engineered using transcription factor bindings sites from strong promoters (-300 to -669 bp) and (-300 to -579 bp), and employed to co-overexpress squalene and ethanol pathways in The FSE strain overexpressing the key genes of the squalene pathway accumulated 56.20 mg/L squalene, a 16.43-fold higher than wild type strain (WS). The biogenesis of lipid droplets was stimulated by overexpressing and produced 106 mg/L squalene in the FSE strain. and repressible promoters were also characterized and employed to downregulate the expression of which also enhanced the production of squalene in FSE strain up to 42.85- (148.67 mg/L) and 73.49-fold (255.11 mg/L) respectively. The FSE strain was further engineered by overexpressing the key genes of the ethanol pathway and produced 40.2 mg/mL ethanol in the FSE1 strain, 3.23-fold higher than the WS strain. The FSE1 strain also self-downregulated the expression of the FA pathway up to 73.9%, perhaps by downregulating the expression of by 2.24-fold. We demonstrate the successful tuning of the strength of yeast promoters and highest coproduction of squalene and ethanol in yeast, and present as a novel metabolic regulator that can be manipulated to divert the metabolic flux from the non-essential pathway to engineered pathways.
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http://dx.doi.org/10.3390/metabo10020056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074498PMC
February 2020

Enhancing the Antibacterial Activity of Erythromycin with Titanium Dioxide Nanoparticles against MRSA.

Curr Pharm Biotechnol 2020 ;21(10):948-954

Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus 22060, Pakistan.

Background: Staphylococcus aureus (S. aureus) is the most common infectious agent in the community and hospitals. Infections with S. aureus are now becoming difficult to be treated by using conventional antibiotics due to its emerging methicillin-resistant S. aureus (MRSA) strain.

Objective: In the present study, MRSA was isolated from clinical samples and evaluated for resistance against different antibiotics, TiO2 nanoparticles, and their combinations.

Methods: Clinical samples were collected from Ayub Medical Complex (AMC), Abbottabad, Pakistan, and identified by different biochemical tests and polymerase chain reactions (PCR). Kirby-Bauer disk diffusion method was performed to evaluate antimicrobial susceptibility. Minimum Inhibitory Concentration (MIC) of ampicillin, ciprofloxacin, erythromycin, and vancomycin was found out by agar dilution method while the broth dilution method was used for the MIC of TiO2 nanoparticles and their combinations with erythromycin.

Results: All 13/100 (13%) MRSA were successfully identified. All isolates were susceptible to quinupristin/ dalfopristin, teicoplanin, and vancomycin, while the highest resistance was seen with erythromycin, penicillin, and tetracycline. MIC showed high resistance against ampicillin (0.25-512 mg/L) and erythromycin (0.25-1024 mg/L).

Conclusion: The MIC value of 2 mM TiO2 nanoparticles was found to be the most effective concentration after 12 h of incubation, while the combination of erythromycin with 3 mM TiO2 nanoparticles was found to be more potent which significantly lowered down the MIC of erythromycin to 2-16 mg/L.
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http://dx.doi.org/10.2174/1389201021666200128124142DOI Listing
October 2020

Synthesis, Characterization and Safety Profiling of Eudragit-Based pHResponsive Hydrogels: A Promising Platform for Colonic Delivery of Losartan Potassium.

Curr Drug Deliv 2019 ;16(6):548-564

Department of Pharmacy, COMSATS University Islamabad, Abbottabad campus 22060, Pakistan.

Objective: The aim of the present study was to design an efficient delivery system with an anticipated swelling and drug release properties for a prolonged drug release as well as to target colon for various hydrophilic drugs.

Method: For this purpose, the pH-responsive hydrogel comprising a combination of Eudragit and acrylic acid was formed. The hydrogels were characterized for spectral (FTIR), thermal (TGA/DSC), structural (XRD), and morphological (SEM) investigations. Oral tolerability was assessed in rabbits for biocompatibility and oral use of the prepared hydrogels.

Results: The results showed that an increased incorporation of Eudragit and cross-linking agent retorted the swelling, drug loading, and drug release properties at both acid (pH 1.2) and basic pH (pH 6.8 and 7.4) , while acrylic acid presented the inverse results. The oral tolerability and toxicity studies depicted that the developed hydrogels were safe up to 3800 mg/kg body weight and caused no hematological or histopathological changes when compared with the control group.

Conclusion: Therefore, the newly developed formulations presented adequate swelling, drug loading, release behavior, and biocompatibility properties and thus can be used as a promising tool for the colonic delivery of various hydrophilic drugs.
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http://dx.doi.org/10.2174/1567201816666190208165511DOI Listing
March 2020

Pectin-based (LA-co-MAA) semi-IPNS as a potential biomaterial for colonic delivery of oxaliplatin.

Int J Pharm 2019 Oct 1;569:118557. Epub 2019 Aug 1.

Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, 22060, Pakistan. Electronic address:

This study describes the fabrication of chemically crosslinked pectin-based LA-co-MAA hydrogels through free radical polymerization technique for the colonic delivery of oxaliplatin. Methylene bisacrylamide was used as a crosslinking agent and ammonium persulfate as an initiator. The successful fabrication and drug loading were confirmed through Fourier transform infrared spectroscopy (FTIR). The thermal investigations through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) suggested the higher thermal stability of the unloaded and OXP-loaded formulations as compared to the raw materials. X-ray diffraction (XRD) analysis showed a decrease in crystallinity after crosslinking. The swelling, drug loading, and drug release were increased with an increase in the concentration of pectin and lactic acid (LA) while methacrylic acid (MAA) displayed an inverse behavior. The in-vitro biodegradability was evaluated against lysozyme and collagenase. The results showed that the hydrogels were stable against blank PBS as compared to lysozyme and collagenase. MTT-assay proved that the blank hydrogels were cytocompatible while free OXP and OXP-loaded hydrogels displayed dose-dependent effect against Vero, MCF-7, and HCT-116 cell lines. The oral tolerability study in rabbits confirmed that the hydrogel dispersion was well-tolerable up to 3650 mg/kg of body weight without causing any histopathological or hematological changes when compared with the control group.
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http://dx.doi.org/10.1016/j.ijpharm.2019.118557DOI Listing
October 2019

Synthesis and characterization of cationic surfactants and their interactions with drug and metal complexes.

Heliyon 2019 Jun 10;5(6):e01885. Epub 2019 Jun 10.

Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.

Two new cationic surfactants, n-hexadecyl-3-methylpyridinium bromide and n-heptadecyl-3-methylpyridinium bromide have been synthesized and characterized in solid state by FT-IR, and in solution by H- and C-NMR spectroscopy. The values of critical micelle concentration (CMC) were determined by UV-visible spectroscopy and conductometry. Interaction of synthesized surfactants with two anionic drugs, i.e., diclofenac sodium {[2-(2, 6-Dichloroanilino) phenyl] acetic acid} and ketoprofen [(RS)-2-(3-benzoylphenyl) propionic acid] was studied by UV-visible spectroscopy. Binding constant (K), Gibb's free energy (ΔG) and number of drug molecules (n) per micelle were also calculated. These synthesized surfactants were proved to be efficient in increasing the solubility and bioavailability of drug molecules. In order to check the carrier efficiency of synthesized surfactants against bioactive coordinate, on complexes, interaction of recently reported bioactive zinc complexes was tested with synthesized cationic surfactants by conductometric measurements. Mole fractions (X) and Gibbs free energy (ΔG) values were also calculated. Both surfactants were further screened for anti-fungal and anti-bacterial activities.
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http://dx.doi.org/10.1016/j.heliyon.2019.e01885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562109PMC
June 2019

Hydatid cyst involving Right Pectoralis Major Muscle: A case report.

Int J Surg Case Rep 2019 6;58:54-56. Epub 2019 Apr 6.

Department of General Surgery, Khyber Teaching Hospital Peshawar, Pakistan. Electronic address:

Background And Aim: Hydatid disease is caused by Echinococcus granulosus; a tapeworm. They rarely affect the musculoskeletal system of the body (<5% of cases). The objective of this case report is to discuss about hydatid cyst disease involving the right pectoralis major muscle.

Case Presentation: Herein, we report a case of a 35 years old lady who came to the outpatient department with a gradually increasing soft swelling at the right upper chest below the clavicle. The final diagnosis was made with the help of a CT scan. The cyst was excised and the area was washed with a scolicidal agent. There was no recurrence after six months of follow up and the patient was doing well.

Conclusion: Hydatid cyst of the Pectoralis Major is rare and must be considered in the differential of any muscular swelling in the body in endemic areas. These cysts should be treated with enucleation/excicion followed by irrigation of the area with a scolicidal agent.
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http://dx.doi.org/10.1016/j.ijscr.2019.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477187PMC
April 2019

Analysis of the Substrate Effect on the Zero-Backward Scattering Condition of a Cu₂O Nanoparticle under Non-Normal Illumination.

Nanomaterials (Basel) 2019 Apr 3;9(4). Epub 2019 Apr 3.

Group of Displays and Photonic Applications (GDAF-UC3M), Carlos III University of Madrid, Leganes, 28911 Madrid, Spain.

The presence of a substrate is one of the most important limitations of the real application of the directional conditions. These conditions allow the control of the spatial distribution of light scattering of nanoparticles. While the zero-forward condition is quite sensitive to any change of the surrounding medium, like the substrate, the zero-backward scattering seems to be less sensitive and very stable under normal illumination. In this letter, the zero-backward scattering condition was investigated on a homogenous Cu₂O spherical subwavelength particle, both theoretically and experimentally. In particular, the influence of the substrate and the impinging direction on the angular distribution of light scattering under this directional condition were studied. We observed that the zero-backward scattering condition was also sensitive to the presence of a substrate beneath when a non-normal illumination was considered. We believe that our finding is quite interesting from a practical point of view and for the real implementation of directional scattering in various applications like cloaking, light-emitting devices, photovoltaic devices, bio-sensing, and many more.
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http://dx.doi.org/10.3390/nano9040536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523745PMC
April 2019

Sequential Optic Neuritis: A Neuromyelitis Optica Spectrum Disorder.

J Coll Physicians Surg Pak 2019 Apr;29(4):379-380

Department of Neurology, Lady Reading Hospital, Peshawar, Pakistan.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune relapsing demyelinating disorder which often leads to severe disability typically targeting spinal cord, optic nerves, and brainstem. Around 75% of NMOSD patients have serum immunoglobulin-G (IgG) autoantibodies to the aquaporin-4 channel (AQP4-IgG). AQP4-IgG antibodies have a central role in new diagnostic criteria of NMOSD. These antibodies have a critical role in long-term management after the first attack. The prevalence of this disorder is lower than multiple sclerosis in European countries. However, NMO makes a substantial proportion of the demyelinating diseases of the central nervous system in countries like Pakistan, where it can be mistaken for multiple sclerosis. Accurate diagnosis is essential as some of the drugs for multiple sclerosis can potentially worsen NMOSD. We present a case of sequential optic neuritis with positive aquaporin 4 antibodies. We have discussed the history, examination findings, diagnostic workups, and treatment of the patient.
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http://dx.doi.org/10.29271/jcpsp.2019.04.379DOI Listing
April 2019

The role of chemosensory protein 10 in the detection of behaviorally active compounds in brown planthopper, Nilaparvata lugens.

Insect Sci 2020 Jun 31;27(3):531-544. Epub 2019 Jan 31.

Hubei Insect Resources Utilization and Sustainable Pest Management Key Laboratory, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, China.

Chemosensory proteins (CSPs) play important roles in insects' chemoreception, although their specific functional roles have not been fully elucidated. In this study, we conducted the developmental expression patterns and competitive binding assay as well as knock-down assay by RNA interference both in vitro and in vivo to reveal the function of NlugCSP10 from the brown planthopper (BPH), Nilaparvata lugens (Stål), a major pest in rice plants. The results showed that NlugCSP10 messenger RNA was significantly higher in males than in females and correlated to gender, development and wing forms. The fluorescence binding assays revealed that NlugCSP10 exhibited the highest binding affinity with cis-3-hexenyl acetate, eicosane, and (+)-β-pinene. Behavioral assay revealed that eicosane displayed attractant activity, while cis-3-hexenyl acetate, similar to (+)-β-pinene significantly repelled N. lugens adults. Silencing of NlugCSP10, which is responsible for cis-3-hexenyl acetate binding, significantly disrupted cis-3-hexenyl acetate communication. Overall, findings of the present study showed that NlugCSP10 could selectively interrelate with numerous volatiles emitted from host plants and these ligands could be designated to develop slow-release mediators that attract/repel N. lugens and subsequently improve the exploration of plans to control this insect pest.
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http://dx.doi.org/10.1111/1744-7917.12659DOI Listing
June 2020

Gelatin-based hydrogels as potential biomaterials for colonic delivery of oxaliplatin.

Int J Pharm 2019 Feb 13;556:236-245. Epub 2018 Dec 13.

Faculty of Pharmacy, The University of Lahore, Pakistan; International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, China.

In present investigation, gelatin-based (AA-co-AMPS) hydrogels were prepared using N, N'-Methylenebisacrylamide (MBA) as a cross-linker and ammonium per sulfate (APS) as an initiator. The successful crosslinking and network formation was confirmed by Fourier transform infrared spectroscopy (FT IR). Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) investigations proved the higher thermal stability and successful entrapment of oxaliplatin (OXP) in the polymeric network. X-ray diffraction (XRD) confirmed the loss in crystallinity of the drug after loading in the hydrogel. Scanning electron microscopy (SEM) revealed the porous surface of the hydrogel. The newly formed hydrogels were responsive to change in pH. The swelling, drug loading and drug release was increased with increase in concentration of acrylic acid (AA) while gelatin and 2-acrylamido 2-methylpronesulfonic acid (AMPS) were found to act inversely. The in-vitro enzymatic degradation study showed that the blank hydrogels were more stable against the blank PBS than the collagenase and lysozyme. MTT-assay proved that the blank hydrogels were cyto-compatible while free OXP as well as OXP-loaded hydrogels showed dose dependent controlled cytotoxicity against Vero, MCF-7 and HCT-116 cell lines. The preliminary safety evaluation and oral tolerability showed that the hydrogel suspension was biocompatible and well tolerable upto 4000 mg/kg of body weight without causing any hematological or histopathological changes in rabbits.
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http://dx.doi.org/10.1016/j.ijpharm.2018.12.020DOI Listing
February 2019

Natural and synthetic materials based CMCh/PVA hydrogels for oxaliplatin delivery: Fabrication, characterization, In-Vitro and In-Vivo safety profiling.

Int J Biol Macromol 2019 Feb 30;122:538-548. Epub 2018 Oct 30.

Department of Pharmacy, COMSATS University, Islamabad, (Abbottabad campus 22060), Pakistan. Electronic address:

In this study, the chemically crosslinked hydrogels of carboxymethyl chitosan and polyvinyl alcohol were fabricated by the free radical polymerization. Successful polymerization was confirmed by Fourier transform infrared spectroscopy, while x-ray diffraction, thermogravimetric analysis, and differential scanning calorimetric measurements helped in investigating crystallinity and thermal behavior of the products. Morphological characterization was performed by scanning electron microscopy. The increased incorporation of carboxymethyl chitosan and polyvinyl alcohol enhanced the swelling, drug loading, and in-vitro drug release while crosslinking agent acted inversely. The blanked hydrogels were cytocompatible while oxaliplatin loaded hydrogels showed dose-dependent controlled cytotoxicity against HCT-116 and MCF-7. Oral biocompatibility in albino rabbits showed that the hydrogel suspension was tolerable up to 3600 mg/kg as no toxic or histopathological changes were observed upon comparison with the control group. Results of the studies confirmed that the developed hydrogels can be a potential candidate for controlled oxaliplatin delivery and targeting in cancer therapy.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.10.203DOI Listing
February 2019

Facile Synthesis of Chitosan Based-(AMPS-co-AA) Semi-IPNs as a Potential Drug Carrier: Enzymatic Degradation, Cytotoxicity, and Preliminary Safety Evaluation.

Curr Drug Deliv 2019 ;16(3):242-253

Department of Pharmacy, COMSATS University, Islamabad (Abbottabad campus 22060), Pakistan.

Objective: The study describes the development of chitosan-based (AMPS-co-AA) semi-IPN hydrogels using free radical polymerization technique.

Methods: The resulting hydrogels were characterized using Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), X-Ray diffraction (XRD), and Scanning Electron Microscopy (SEM). The successful crosslinking of chitosan, 2- Acrylamido-2-Methylpropane Sulfonic Acid (AMPS), and Acrylic Acid (AA) was confirmed by FT IR. Unloaded and drug-loaded hydrogels exhibited higher thermal stability after crosslinking compared to the individual components. XRD confirmed the decrease in crystallinity after hydrogel formation and molecular dispersion of Oxaliplatin (OXP) in the polymeric network. SEM showed rough, vague and nebulous surface resulting from crosslinking and loading of OXP.

Results: The experimental results revealed that swelling and drug release were influenced by the pH of the medium being low at acidic pH and higher at basic pH. Increasing the concentration of chitosan and AA enhanced the swelling, drug loading and drug release while AMPS was found to act inversely.

Conclusion: It was confirmed that the hydrogels were degraded more by specific enzyme lysozyme as compared to the non-specific enzyme collagenase. In-vitro cytotoxicity suggested that the unloaded hydrogels were non-cytotoxic while crude drug and drug-loaded hydrogel exhibited dose-dependent cytotoxicity against HCT-116 and MCF-7. Results of acute oral toxicity on rabbits demonstrated that the hydrogels are non-toxic up to 3900 mg/kg after oral administration, as no toxicity or histopathological changes were observed in comparison to control rabbits. These pH-sensitive hydrogels appear to provide an ideal basis as a safe carrier for oral drug delivery.
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http://dx.doi.org/10.2174/1567201815666181024152101DOI Listing
June 2019

Fabrication and in vitro characterization of HPMC-g-poly(AMPS) hydrogels loaded with loxoprofen sodium.

Int J Biol Macromol 2018 Dec 1;120(Pt B):1624-1631. Epub 2018 Oct 1.

Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, 22060, Pakistan. Electronic address:

The aim of this study was to prepare hydroxypropyl-methyl cellulose (HPMC)-K15 based hydrogels via free radical polymerization using 2‑acrylamido-2‑methyl propane sulphonic acid (AMPS) as a monomer and N,N'-methylene bisacrylamide (MBAAm) as a crosslinker. Loxoprofen sodium was chosen as a model drug and successfully loaded in hydrogel discs. Sol-gel, porosity, loading efficiency, and the in vitro drug release analysis were carried out to evaluate its drug delivery potential. HMPC-g-poly(AMPS) hydrogels were characterized by using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) approaches. Maximum swelling and drug release were observed at pH 7.4. Kinetic modelling suggested that drug release followed first-order kinetics with the non-Fickian mechanism. FTIR and DSC confirmed the formation of new hydrogels. SEM micrographs confirmed uneven, rough, and partially porous type of surface. These results suggested that HMPC-g-poly(AMPS) hydrogels can be a prospective pH-responsive carrier for delivery of water-soluble drugs, such as loxoprofen sodium.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.09.184DOI Listing
December 2018

Engineering the optical properties of dielectric nanospheres by resonant modes.

Nanotechnology 2018 Dec 27;29(50):505204. Epub 2018 Sep 27.

School of Electronic Engineering and Optoelectronic Technology, Nanjing University of Science and Technology, Nanjing, 210094, Jiangsu, People's Republic of China.

Recent progress in nanoscale optical physics is associated with the development of a new branch of nanophotonics exploring strong Mie resonances in dielectric nanoparticles with high refractive index (HRI). The high-index resonant dielectric nanostructures form building blocks for novel photonic meta-devices with low losses and advanced functionalities. In this work, we investigate the size effect of an HRI cuprous oxide (CuO) nanosphere on the optical properties of the structure, such as, scattering and absorption spectrum. We also experimentally demonstrate that the scattering field can be significantly engineered by tuning the radius of CuO. It is found that the resonant eigenmodes supported by the nanospheres play the dominant role in the absorption and scattering characteristic of the structure. From the perspective of eigenmodes, we can immediately find the right structure parameters to realize strong absorption (scattering) at either single wavelength or broadband wavelength. Furthermore, the multipole expansion method has been applied to explore the physical nature (i.e. electric mode or magnetic mode) of the eigenmode as well as contributions from different modes.
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http://dx.doi.org/10.1088/1361-6528/aae4d2DOI Listing
December 2018

Detection, virulence and genetic diversity of Fusarium species infecting tomato in Northern Pakistan.

PLoS One 2018 20;13(9):e0203613. Epub 2018 Sep 20.

Mid-Florida Research and Education Center, Department of Plant Pathology, University of Florida, Institute of Food and Agricultural Sciences, Apopka, FL, United States of America.

In addition to the well-known Fusarium oxysporum f.sp. lycopersici, several other Fusarium species are known to cause extensive worldwide crop losses in tomatoes. Prevalence and identities of Fusarium species infecting tomatoes in Northwest Pakistan is currently not known. In this study, we surveyed and characterized Fusarium species associated with symptomatic tomatoes in Northwest Pakistan using morphological and molecular analyses. Pathogenicity tests revealed varying degrees of virulence with some Fusarium sp. causing severe disease symptoms whereas others displaying mild symptoms. Molecular identification based on Internal Transcribed Spacer (ITS) region and TEF-1α gene sequencing classified all isolates into four major species with a majority (68.9%) belonging to Fusarium incarnatum-equiseti species complex (FIESC), followed by F. graminearum (20.7%), F. acuminatum (6.8%), and F. solani (6.8%). ISSR analyses revealed substantial genetic variability among all the Fusarium population infecting tomatoes. Genetic distance between populations from the central region and the type strain F.o. f.sp. lycopersici from Florida was the highest (0.3662), whereas between the south and central region was the lowest (0.0298), which showed that genetic exchange is negatively effected by distance. High genetic variability suggests that these Fusarium species have the potential to become a major production constraint for tomato growers. Findings in this report would greatly facilitate identification of Fusarium species in developing countries and would provide groundwork for devising and implementing disease management measures for minimizing losses caused by Fusarium species in tomatoes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203613PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147440PMC
February 2019

Clinico-epidemiological Characteristics of Corrosive Ingestion: A Cross-sectional Study at a Tertiary Care Hospital of Multan, South-Punjab Pakistan.

Cureus 2018 May 29;10(5):e2704. Epub 2018 May 29.

Thoracic and General Surgery, Nishtar Medical University, Multan, PAK.

Introduction Corrosive ingestion is a grave public health problem. It is a medical emergency and shows diverse clinical presentations. The ingestion of corrosive substances has devastating effects on upper gastrointestinal and respiratory tracts and the corrosive injury is associated with numerous life-threatening complications. The present study aims to explore the clinico-epidemiological characteristics of patients of corrosive ingestion presenting at a tertiary care hospital of Multan, Pakistan. Method The target study population consists of all the patients with primary diagnosis of corrosive ingestion who presented to the department of thoracic surgery, Nishtar Medical University Hospital Multan, Pakistan, from January 2016 to December 2017. The follow-up cases and the cases with ingestion of substances other than corrosives were not included in the study. All the included cases were evaluated by detailed history, thorough physical examination and the necessary investigations. The post-cor-rosive tissue damage was classified accord-ing to Zargar's classification system. All the demographic data and other variables were measured and recorded using a Performa. The data were analyzed by using computer program SPSS 21 version. Results The total study population was 206 patients. There were 135 females (65.5%) and 71 male patients (34.5%). Age ranged from 2 to 42 years (mean 23.44 ± 7.19). Only seven cases were found in the age group of 2-7 years. The residents of rural areas showed a slightly increased inclination towards corrosive ingestion. One hundred and ten cases were unmarried (53.4%) while 90 patients were married (43.7%). The incidence of corrosive ingestion was much high in illiterate/less educated patients belonging to the groups of lower socio-economic status. One hundred and ninety-seven patients ingested corrosive substances deliberately with the suicidal intention (95.6%). The acid used as bathroom cleaner and the laundry bleaches were the most commonly used corrosive agents. In 166 cases the corrosive materials were already present at home for domestic purposes (80.6%), but 18 subjects particularly purchased these corrosive substances to commit suicide. The quantity of ingested material ranged between 10 ml and 150 ml with a mean of 42.6 ml ± 33.2. The shortest hospital stay was one day, and the longest one was 60 days. Esophagus and oropharyngeal area were the most common site which sustained the corrosive injury, whereas corrosive injury to duodenum was least frequent (34.5 %). Conclusion Corrosive ingestion is a serious medical problem and it requires a multidisciplinary approach and a good coordination between different medical specialists. Underprivileged teenager females of rural areas are more likely to ingest corrosive materials with suicidal intention. In most of the ingestions, household cleaning products are used. Only the patients with severe corrosive injury should be admitted to intensive care units. Enforcing regulations for the manufacturers of household cleaning products can significantly reduce the incidence of this potentially fatal condition.
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http://dx.doi.org/10.7759/cureus.2704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063384PMC
May 2018

Vanek's tumor as an unusual cause of ileo-ileal intessuception - A unique case report.

Ann Med Surg (Lond) 2018 Aug 26;32:14-17. Epub 2018 Jun 26.

Department of General Surgery, Khyber Teaching Hospital Peshawar, Pakistan.

Background And Aim: Vanek's tumor is a rare solitary lesion that is non-neoplastic, and arises from the submucosa of the gut. The most commonly affected sites are the stomach and the ileum [1]. IFP causing intestinal obstruction is uncommon and that ileo-ileal intussusception has been reported in the literature rarely. We present a case of an ileo-ileal intessuception in a patient who presented with acute on chronic pain abdomen and anorexia. CT abdomen & pelvis revealed a 46 × 36 mm intraluminal mass in the left iliac fossa causing ileo-ileal intussusception.

Case Presentation: A 60 years old gentleman was brought to the A&E with a history of intestinal obstruction. He was examined and admitted to the surgical unit. CBC revealed unique feature of reactive thrombocytosis apart from a low hemoglobin and a raised TLC. His CT scan demonstrated findings of ileo-ileal intussusception. After an informed written consent, patient underwent an exploratory laparotomy and had resection and anastomosis of the bowel. Histopathology of the specimen revealed findings compatible with IFP. Patient made an uneventful recovery post-operatively and was sent home in the next few days. On follow-up, the patient was doing well and had no complaints of abdominal pain or anorexia.

Conclusion: Vanek's tumor although a rare entity, should be considered in each case of acute abdomen and physicians and surgeons need to have a high degree of suspicion in such cases. Moreover, IFP can cause reactive thrombocytosis that gets resolved after a post-operative period of 6-8 weeks.
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http://dx.doi.org/10.1016/j.amsu.2018.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039895PMC
August 2018

Total Avulsed Ear Management With Radial Forearm Free Flap.

J Oral Maxillofac Surg 2018 Aug 28;76(8):1745.e1-1745.e4. Epub 2018 Apr 28.

Consultant Oral and Maxillofacial Surgeon, KRL General Hospital Islamabad, Islamabad, Pakistan.

Avulsive injuries to the ear are extremely challenging to treat. The literature documents numerous ways to manage such injuries. This report describes a case of total auricular cartilaginous avulsion that occurred during a motor vehicle accident. The avulsed segment had an ischemia time longer than 8 hours by the time of presentation at the authors' tertiary care facility. The avulsed segment was de-epithelialized and embedded into the volar forearm. After a healing period of 6 months, a radial forearm free flap was harvested and the ear was reconstructed. After ensuring good flap uptake and adequate primary healing, the flap was debulked and reshaped at 4 months after inset.
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http://dx.doi.org/10.1016/j.joms.2018.04.022DOI Listing
August 2018

Lethal toxic Dose (i.p LD50), total protein contents and comparative hemolytic potential of (99mTc labeled & non-labeled) Naja naja karachiensis venom.

Pak J Pharm Sci 2018 Mar;31(2(Suppl.)):685-689

Kazan (Volga Region) Federal University, Institute of Fundamental Medicine and Biology, Department of Genetics, Kremlevskaya Street, Kazan, Tatarstan, Russia.

Recent recognition about snake bite envenomation on June, 2017 as neglected tropical disease under category-A by World Health Organization advocated again its undeniable importance. Present circumstances reasoned to work on a neglected subspecies of Naja naja, i.e., Naja naja karachiensis (N. n. karachensis) has been documented for frequent deaths in Pakistan. In this study median lethal toxic dose (LD) was determined intraperitoneally in Swiss albino mice and was found to be 2.0µg/g (2.0mg/kg) equal in potency to Naja pallida (red spitting African cobra). Total protein contents (188±0.011µg / 200µg of dry weight) were high enough (94%) to represent an arsenal of proteins. Furthermore, Tc was labeled 99.9% with venom and didn't find to alter hemolytic activity of venom in dose dependent manner at 125μg/ml (p>0.5), 250 μg/ml (p>0.1) and 500 μg/ml (p>0.1) when compared with its crude form. Present work will pave the way for proteomics study in effective production of antidote against specific species of snakes as dare demand of it has been felt since long period of time in Pakistan.
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March 2018

Natural and synthetic polymer-based smart biomaterials for management of ulcerative colitis: a review of recent developments and future prospects.

Drug Deliv Transl Res 2019 04;9(2):595-614

Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, 22060, Pakistan.

Ulcerative colitis (UC) is an inflammatory disease of the colon that severely affects the quality of life of patients and usually responds well to anti-inflammatory agents for symptomatic relief; however, many patients need colectomy, a surgical procedure to remove whole or part of the colon. Though various types of pharmacological agents have been employed for the management of UC, the lack of effectiveness is usually predisposed to various reasons including lack of target-specific delivery of drugs and insufficient drug accumulation at the target site. To overcome these glitches, many researchers have designed and characterized various types of versatile polymeric biomaterials to achieve target-specific delivery of drugs via oral route to optimize their targeting efficiency to the colon, to improve drug accumulation at the target site, as well as to ameliorate off-target effects of chemotherapy. Therefore, the aim of this review was to summarize and critically discuss the pharmaceutical significance and therapeutic feasibility of a wide range of natural and synthetic biomaterials for efficient drug targeting to colon and rationalized treatment of UC. Among various types of biomaterials, natural and synthetic polymer-based hydrogels have shown promising targeting potential due to their innate pH responsiveness, sustained and controlled release characteristics, and microbial degradation in the colon to release the encapsulated drug moieties. These characteristic features make natural and synthetic polymer-based hydrogels superior to conventional pharmacological strategies for the management of UC.
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http://dx.doi.org/10.1007/s13346-018-0512-xDOI Listing
April 2019

Light scattering by subwavelength CuO particles.

Nanotechnology 2017 Mar 3;28(13):134002. Epub 2017 Feb 3.

School of Electronics Engineering and Opto-electronic Technology, Nanjing University of Science and Technology, Nanjing, 210094, People's Republic of China.

Novel metamaterials with new capabilities to manipulate light may be used by considering basic building blocks with new optical properties. This is the case with resonant magneto-dielectric particles. In this work, the resonant response of a high-dielectric CuO subwavelength particle is analyzed, both analytically and experimentally. The emergence of electric and magnetic resonances and their interferential effects, producing directional behaviors, can be used in a new generation of metamaterials, as well as new integrated optical devices.
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http://dx.doi.org/10.1088/1361-6528/aa5e3cDOI Listing
March 2017

FORMULATION, EVALUATION AND IN VITRO DISSOLUTION PERFORMANCE OF ENALAPRIL MALEATE SUSTAINED RELEASE MATRICES: EFFECT OF POLYMER COMPOSITION AND VISCOSITY GRADE.

Acta Pol Pharm 2016 07;73(4):1037-1043

The present study aimed at developing the sustained release matrix tablets of enalapril maleate and evaluating the effect of polymer concentration and viscosity grade on drug release. The sustained release enalapril maleate tablets were successfully formulated by direct compression method using nonionic cellulose ethers HPMC K15, HPMC K100 and HPC polymers either alone or in combination. In-vitio drug release study was carried out in phosphate buffer (pH 6.8) for a period of 24 h following USP dissolution apparatus II i.e., paddle apparatus. Model dependent approaches like zero-order, first order, Higuchi's model and Korsmeyer-Peppas model were used to assess drug release from various formulations. All the three polymers alone or in combination sustained the drug release. The drug release characteristics from HPMC and HPC polymer followed zero order release kinetics except for 45% concentration of all polymers alone or in combination where by the drug release followed Higuchi's model. In all cases, the drug release mechanism was both diffusion as well as erosion.
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July 2016
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