Displaying publications 61 - 80 of 95 in total

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  1. Mukheem A, Shahabuddin S, Akbar N, Anwar A, Sarih NM, Sudesh K, et al.
    Appl Microbiol Biotechnol, 2020 Apr;104(7):3121-3131.
    PMID: 32060693 DOI: 10.1007/s00253-020-10416-2
    Antibiotic resistance in pathogenic bacteria is a major health challenge, as Infectious Diseases Society of America (IDSA) has recognized that the past simply drugs susceptible pathogens are now the most dangerous pathogens due to their nonstop growing resistance towards conventional antibiotics. Therefore, due to the emergence of multi-drug resistance, the bacterial infections have become a serious global problem. Acute infections feasibly develop into chronic infections because of many factors; one of them is the failure of effectiveness of antibiotics against superbugs. Modern research of two-dimensional nanoparticles and biopolymers are of great interest to attain the intricate bactericidal activity. In this study, we fabricated an antibacterial nanocomposite consisting of representative two-dimensional molybdenum disulfide (2D MoS2) nanoparticles. Polyhydroxyalkanoate (PHA) and chitosan (Ch) are used to encapsulate MoS2 nanoparticles into their matrix. This study reports the in vitro antibacterial activity and host cytotoxicity of novel PHA-Ch/MoS2 nanocomposites. PHA-Ch/MoS2 nanocomposites were subjected to time-dependent antibacterial assays at various doses to examine their antibacterial activity against multi-drug-resistant Escherichia coli K1 (Malaysian Type Culture Collection 710859) and methicillin-resistant Staphylococcus aureus (MRSA) (Malaysian Type Culture Collection 381123). Furthermore, the cytotoxicity of nanocomposites was examined against spontaneously immortalized human keratinocyte (HaCaT) cell lines. The results indicated significant antibacterial activity (p value
  2. Mungroo MR, Khan NA, Anwar A, Siddiqui R
    Int Microbiol, 2021 Aug 09.
    PMID: 34368912 DOI: 10.1007/s10123-021-00201-0
    Pathogenic free-living amoebae are known to cause fatal central nervous system infections with extremely high mortality rates. High selectivity of the blood-brain barrier hampers delivery of drugs and untargeted delivery of drugs can cause severe side effects. Nanovehicles can be used for targeted drug delivery across the blood-brain barrier. Inorganic nanoparticles have been explored as carriers for various biomedical applications and can be modified with various ligands for efficient targeting and cell selectivity while lipid-based nanoparticles have been extensively used in the development of both precision and colloidal nanovehicles. Nanomicelles and polymeric nanoparticles can also serve as nanocarriers and may be modified so that responsiveness of the nanoparticles and release of the loads are linked to specific stimuli. These nanoparticles are discussed here in the context of the treatment of central nervous system infections due to pathogenic amoebae. It is anticipated that these novel strategies can be utilized in tandem with novel drug leads currently in the pipeline and yield in the development of much needed treatments against these devastating parasites.
  3. Mungroo MR, Shahbaz MS, Anwar A, Saad SM, Khan KM, Khan NA, et al.
    ACS Chem Neurosci, 2020 08 19;11(16):2438-2449.
    PMID: 31961126 DOI: 10.1021/acschemneuro.9b00596
    Naegleria fowleri and Balamuthia mandrillaris are protist pathogens that infect the central nervous system, causing primary amoebic meningoencephalitis and granulomatous amoebic encephalitis with mortality rates of over 95%. Quinazolinones and their derivatives possess a wide spectrum of biological properties, but their antiamoebic effects against brain-eating amoebae have never been tested before. In this study, we synthesized a variety of 34 novel arylquinazolinones derivatives (Q1-Q34) by altering both quinazolinone core and aryl substituents. To study the antiamoebic activity of these synthetic arylquinazolinones, amoebicidal and amoebistatic assays were performed against N. fowleri and B. mandrillaris. Moreover, amoebae-mediated host cells cytotopathogenicity and cytotoxicity assays were performed against human keratinocytes cells in vitro. The results revealed that selected arylquinazolinones derivatives decreased the viability of B. mandrillaris and N. fowleri significantly (P < 0.05) and reduced cytopathogenicity of both parasites. Furthermore, these compounds were also found to be least cytotoxic against HaCat cells. Considering that nanoparticle-based materials possess potent in vitro activity against brain-eating amoebae, we conjugated quinazolinones derivatives with silver nanoparticles and showed that activities of the drugs were enhanced successfully after conjugation. The current study suggests that quinazolinones alone as well as conjugated with silver nanoparticles may serve as potent therapeutics against brain-eating amoebae.
  4. Mungroo MR, Anwar A, Khan NA, Siddiqui R
    Mini Rev Med Chem, 2019;19(12):980-987.
    PMID: 30868950 DOI: 10.2174/1389557519666190313161854
    Pathogenic free-living amoeba are known to cause a devastating infection of the central nervous system and are often referred to as "brain-eating amoebae". The mortality rate of more than 90% and free-living nature of these amoebae is a cause for concern. It is distressing that the mortality rate has remained the same over the past few decades, highlighting the lack of interest by the pharmaceutical industry. With the threat of global warming and increased outdoor activities of public, there is a need for renewed interest in identifying potential anti-amoebic compounds for successful prognosis. Here, we discuss the available chemotherapeutic options and opportunities for potential strategies in the treatment and diagnosis of these life-threatening infections.
  5. Mungroo MR, Anwar A, Khan NA, Siddiqui R
    ACS Omega, 2020 Jun 02;5(21):12467-12475.
    PMID: 32548431 DOI: 10.1021/acsomega.0c01305
    Balamuthia mandrillaris and Naegleria fowleri are free-living amoebae that cause infection of the central nervous system, granulomatous amoebic encephalitis (GAE) and primary amoebic meningoencephalitis (PAM), respectively. The fact that mortality rates for cases of GAE and PAM are more than 95% indicates the need for new therapeutic agents against those amoebae. Considering that curcumin exhibits a wide range of biological properties and has shown efficacy against Acanthamoeba castellanii, we evaluated the amoebicidal properties of curcumin against N. fowleri and B. mandrillaris. Curcumin showed significant amoebicidal activities with an AC50 of 172 and 74 μM against B. mandrillaris and N. fowleri, respectively. Moreover, these compounds were also conjugated with gold nanoparticles to further increase their amoebicidal activities. After conjugation with gold nanoparticles, amoebicidal activities of the drugs were increased by up to 56 and 37% against B. mandrillaris and N. fowleri, respectively. These findings are remarkable and suggest that clinically available curcumin and our gold-conjugated curcumin nanoparticles hold promise in the improved treatment of fatal infections caused by brain-eating amoebae and should serve as a model in the rationale development of therapeutic interventions against other infections.
  6. Mustafa S, Qiao Y, Yan X, Anwar A, Hao T, Rana S
    Front Psychol, 2022;13:956281.
    PMID: 35936293 DOI: 10.3389/fpsyg.2022.956281
    During the COVID-19 pandemic, online teaching modes were found vital to continue students' learning process, but sustainable implementation of online teaching models is an area of concern for policymakers. Psychiatrists are also eager to know students' behavior toward learning and modes of teaching during COVID-19. We have drawn a model based on the big five personality traits to study students' satisfaction with online teaching modes and their adoption intentions toward online teaching modes. We have collected data from 718 bachelor's and master's level students from four different universities. We have applied the SEM-ANN dual-stage approach to test personality traits' influence and ranked them based on their normalized importance. The results revealed that agreeableness, conscientiousness, neuroticism, and openness positively influence students' satisfaction with online teaching models, but that extraversion negatively influences their satisfaction. Agreeableness, extraversion, and neuroticism positively impact, but openness negatively influences. Conscientiousness does not affect adoption intention. Furthermore, agreeableness is the most significant, and conscientiousness is the least important factor for students to adopt online teaching modes. The findings of the study have useful perceptiveness for educational policymakers, academics, and psychiatrists.
  7. Rahim NI, Mohammed BS, Al-Fakih A, Wahab MMA, Liew MS, Anwar A, et al.
    Materials (Basel), 2020 Jun 22;13(12).
    PMID: 32580327 DOI: 10.3390/ma13122804
    Deep beams are more susceptible to shear failure, and therefore reparation is a crucial for structural reinforcements. Shear failure is structural concrete failure in nature. It generally occurs without warning; however, it is acceptable for the beam to fail in bending but not in shear. The experimental study presented the structural behavior of the deep beams of reinforced concrete (RC) that reinforces the web openings with externally connected carbon fiber reinforced polymer (CFRP) composite in the shear zone. The structural behavior includes a failure mode, and cracking pattern, load deflection responses, stress concentration and the reinforcement factor were investigated. A total of nine reinforced concrete deep beams with openings strengthened with CFRP and one control beam without an opening have been cast and tested under static four-point bending load till failure. The experimental results showed that the increase the size of the opening causes an increase in the shear strength reduction by up to 30%. Therefore, the larger the openings, the lower the capability of load carriage, in addition to an increase in the number of CFRP layers that could enhance the load carrying capacity. Consequently, utilization of the CFRP layer wrapping technique strengthened the shear behavior of the reinforced concrete deep beams from about 10% to 40%. It was concluded that the most effective number of CFRP layers for the deep beam with opening sizes of 150 mm and 200 mm were two layers and three layers, respectively.
  8. Rajendran K, Anwar A, Khan NA, Aslam Z, Raza Shah M, Siddiqui R
    ACS Chem Neurosci, 2020 08 19;11(16):2431-2437.
    PMID: 31347828 DOI: 10.1021/acschemneuro.9b00289
    Naegleria fowleri (N. fowleri) causes primary amoebic meningoencephalitis (PAM) which almost always results in death. N. fowleri is also known as "brain-eating amoeba" due to its literal infestation of the brain leading to an inflammatory response in the brain tissues. Currently, there is no single drug that is available to treat PAM, and most treatments are combinations of antifungal, anticancer, and anti-inflammatory drugs. Recently nanotechnology has gained attention in chemotherapeutic research converging on drug delivery, while oleic acid (OA) has shown positive effects on the human immune system and inflammatory processes. In continuation of our recent research in which we reported the effects of oleic acid conjugated with silver nanoparticles (OA-AgNPs) against free-living amoeba Acanthamoeba castellanii, in this report, we show their antiamoebic effects against N. fowleri. OA alone and its nanoconjugates were tested against the amoeba by using amoebicidal and host cell cytopathogenicity assays. Trypan blue exclusion assay was used to determine cell viability. The results revealed that OA-AgNPs exhibited significantly enhanced antiamoebic effects (P < 0.05) against N. fowleri as compared to OA alone. Evidently, lactate dehydrogenase release shows reduced N. fowleri-mediated host cell cytotoxicity. Based on our study, we anticipate that further studies on OA-AgNPs could potentially provide an alternative treatment of PAM.
  9. Rajendran K, Anwar A, Khan NA, Shah MR, Siddiqui R
    ACS Chem Neurosci, 2019 06 19;10(6):2692-2696.
    PMID: 30970208 DOI: 10.1021/acschemneuro.9b00111
    Primary amoebic meningoencephalitis (PAM), a deadly brain infection, is caused by brain-eating amoeba Naegleria fowleri. The current first line of treatment against PAM is a mixture of amphotericin B, rifampin, and miltefosine. Since, no single effective drug has been developed so far, the mortality rate is above 95%. Moreover, severe adverse side effects are associated with these drugs. Nanotechnology has provided several advances in biomedical applications especially in drug delivery and diagnosis. Herein, for the first time we report antiamoebic properties of cinnamic acid (CA) and gold nanoparticles conjugated with CA (CA-AuNPs) against N. fowleri. CA-AuNPs were successfully synthesized by sodium borohydride reduction of tetrachloroauric acid. Size and morphology were determined by atomic force microscopy (AFM) while the surface plasmon resonance band was analyzed by ultraviolet-visible (UV-vis) spectrophotometry for the characterization of the nanoparticles. Amoebicidal and cytopathogenicity (host cell cytotoxicity) assays revealed that both CA and CA-AuNPs displayed significant anti- N. fowleri properties ( P < 0.05), whereas nanoparticles conjugation further enhanced the anti- N. fowleri effects of CA. This study established a potential drug lead, while CA-AuNPs appear to be promising candidate for drug discovery against PAM.
  10. Rajendran K, Anwar A, Khan NA, Siddiqui R
    ACS Chem Neurosci, 2017 12 20;8(12):2626-2630.
    PMID: 29206032 DOI: 10.1021/acschemneuro.7b00430
    The overall aim of this study was to determine whether conjugation with silver nanoparticles enhances effects of available drugs against primary amoebic meningoencephalitis due to Naegleria fowleri. Amphotericin B, Nystatin, and Fluconazole were conjugated with silver nanoparticles, and synthesis was confirmed using UV-visible spectrophotometry. Atomic force microscopy determined their size in range of 20-100 nm. To determine amoebicidal effects, N. fowleri were incubated with drugs-conjugated silver nanoparticles, silver nanoparticles alone, and drugs alone. The findings revealed that silver nanoparticles conjugation significantly enhanced antiamoebic effects of Nystatin and Amphotericin B but not Fluconazole at micromolar concentrations, compared with the drugs alone. For the first time, our findings showed that silver nanoparticle conjugation enhances efficacy of antiamoebic drugs against N. fowleri. Given the rarity of the disease and challenges in developing new drugs, it is hoped that modifying existing drugs to enhance their antiamoebic effects is a useful avenue that holds promise in improving the treatment of brain-eating amoebae infection due to N. fowleri.
  11. Rajendran K, Ahmed U, Meunier AC, Shaikh MF, Siddiqui R, Anwar A
    ACS Chem Neurosci, 2023 Dec 06;14(23):4105-4114.
    PMID: 37983556 DOI: 10.1021/acschemneuro.3c00258
    Naegleria fowleri is one of the free-living amoebae and is a causative agent of a lethal and rare central nervous system infection called primary amoebic meningoencephalitis. Despite the advancement in antimicrobial chemotherapy, the fatality rate in the reported cases is more than 95%. Most of the treatment drugs used against N. fowleri infection are repurposed drugs. Therefore, a large number of compounds have been tested against N. fowleri in vitro, but most of the compounds showed high toxicity. To overcome this, we evaluated the effectiveness of naturally occurring terpene compounds against N. fowleri. In this study, we evaluated the antiamoebic potential of natural compounds including Thymol, Borneol, Andrographolide, and Forskolin againstN. fowleri. Thymol showed the highest amoebicidal activity with IC50/24 h at 153.601 ± 19.6 μM. Two combinations of compounds Forskolin + Thymol and Forskolin + Borneol showed a higher effect on the viability of trophozoites as compared to compounds alone and hence showed a synergistic effect. The IC50 reported for Forskolin + Thymol was 81.30 ± 6.86 μM. Borneol showed maximum cysticidal activity with IC50/24 h at 192.605 ± 3.01 μM. Importantly, lactate dehydrogenase release testing revealed that all compounds displayed minimal cytotoxicity to human HaCaT, HeLa, and SH-SY5Y cell lines. The cytopathogenicity assay showed that Thymol and Borneol also significantly reduced the host cell cytotoxicity of pretreated amoeba toward the human HaCaT cell line. So, these terpene compounds hold potential as therapeutic agents against infections caused by N. fowleri and are potentially a step forward in drug development against this deadly pathogen as these compounds have also been reported to cross the blood-brain barrier. Therefore, an in vivo study using animal models is necessary to assess the efficacy of these compounds and the need for further research into the intranasal route of delivery for the treatment of these life-threatening infections.
  12. Rajendran K, Ahmed U, Meunier AC, Shaikh MF, Siddiqui R, Anwar A
    ACS Omega, 2024 Mar 12;9(10):11597-11607.
    PMID: 38497026 DOI: 10.1021/acsomega.3c08844
    Pathogenic Naegleria fowleri (N. fowleri) are opportunistic free-living amoebae and are the causative agents of a very rare but severe brain infection called primary amoebic meningoencephalitis (PAM). The fatality rate of PAM in reported cases is more than 95%. Most of the drugs used againstN. fowleri infections are repurposed drugs. Therefore, a large number of compounds have been tested againstN. fowleri in vitro, but most of the tested compounds showed high toxicity and an inability to cross the blood-brain barrier. Andrographolide, forskolin, and borneol are important natural compounds that have shown various valuable biological properties. In the present study, the nanoconjugates (AND-AgNPs, BOR-AgNPs, and FOR-AgNPs) of these compounds were synthesized and assessed against both stages (trophozoite and cyst) ofN. fowleri for their antiamoebic and cysticidal potential in vitro. In addition, cytotoxicity and host cell pathogenicity were also evaluated in vitro. FOR-AgNPs were the most potent nanoconjugate and showed potent antiamoebic activity againstN. fowleriwith an IC50 of 26.35 μM. Nanoconjugates FOR-AgNPs, BOR-AgNPs, and AND-AgNPs also significantly inhibit the viability of N. fowleri cysts. Cytotoxicity assessment showed that these nanoconjugates caused minimum damage to human keratinocyte cells (HaCaT cells) at 100 μg/mL, while also effectively reducing the cytopathogenicity of N. fowleri trophozoites to the HaCaT cells. The outcomes of our experiments have unveiled substantial potential for AND-AgNPs, BOR-AgNPs, and FOR-AgNPs in the realm of developing innovative alternative therapeutic agents to combat infections caused by N. fowleri. This study represents a significant step forward in the pursuit of advanced strategies for managing such amoebic infections, laying the foundation for the development of novel and more effective therapeutic modalities in the fight against free-living amoebae.
  13. Ramanathan B, Jindal HM, Le CF, Gudimella R, Anwar A, Razali R, et al.
    PLoS One, 2017;12(8):e0182524.
    PMID: 28797043 DOI: 10.1371/journal.pone.0182524
    Rapid progress in next generation sequencing and allied computational tools have aided in identification of single nucleotide variants in genomes of several organisms. In the present study, we have investigated single nucleotide polymorphism (SNP) in ten multi-antibiotic resistant Pseudomonas aeruginosa clinical isolates. All the draft genomes were submitted to Rapid Annotations using Subsystems Technology (RAST) web server and the predicted protein sequences were used for comparison. Non-synonymous single nucleotide polymorphism (nsSNP) found in the clinical isolates compared to the reference genome (PAO1), and the comparison of nsSNPs between antibiotic resistant and susceptible clinical isolates revealed insights into the genome variation. These nsSNPs identified in the multi-drug resistant clinical isolates were found to be altering a single amino acid in several antibiotic resistant genes. We found mutations in genes encoding efflux pump systems, cell wall, DNA replication and genes involved in repair mechanism. In addition, nucleotide deletions in the genome and mutations leading to generation of stop codons were also observed in the antibiotic resistant clinical isolates. Next generation sequencing is a powerful tool to compare the whole genomes and analyse the single base pair variations found within the antibiotic resistant genes. We identified specific mutations within antibiotic resistant genes compared to the susceptible strain of the same bacterial species and these findings may provide insights to understand the role of single nucleotide variants in antibiotic resistance.
  14. Rao K, Abdullah M, Ahmed U, Wehelie HI, Shah MR, Siddiqui R, et al.
    Arch Microbiol, 2024 Mar 04;206(4):134.
    PMID: 38433145 DOI: 10.1007/s00203-024-03854-3
    Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.
  15. Rashid B, Anwar A, Shahabuddin S, Mohan G, Saidur R, Aslfattahi N, et al.
    Materials (Basel), 2021 Aug 04;14(16).
    PMID: 34442891 DOI: 10.3390/ma14164370
    The MXenes are a novel family of 2-D materials with promising biomedical activity, however, their anticancer potential is still largely unexplored. In this study, a comparative cytotoxicity investigation of Ti3C2 MXenes with polypropylene glycol (PPG), and polyethylene glycol (PEG) surface-modified 2-D Ti3C2 MXene flakes has been conducted towards normal and cancerous human cell lines. The wet chemical etching method was used to synthesize MXene followed by a simple chemical mixing method for surface modification of Ti3C2 MXene with PPG and PEG molecules. SEM and XRD analyses were performed to examine surface morphology and elemental composition, respectively. FTIR and UV-vis spectroscopy were used to confirm surface modification and light absorption, respectively. The cell lines used to study the cytotoxicity of MXene and surface-modified MXenes in this study were normal (HaCaT and MCF-10A) and cancerous (MCF-7 and A375) cells. These cell lines were also used as controls (without exposure to study material and irradiation) to measure their baseline cell viability under the same lab environment. The surface-modified MXenes exhibited a sharp reduction in cell viability towards both normal (HaCaT and MCF-10A) and cancerous (MCF-7 and A375) cells but cytotoxicity was more pronounced towards cancerous cell lines. This may be due to the difference in cell metabolism and the occurrence of high pre-existing levels of reactive oxygen species (ROS) within cancerous cells. The highest toxicity towards both normal and cancerous cell lines was observed with PEGylated MXenes followed by PPGylated and bare MXenes. The normal cell's viability was barely above 70% threshold with 250 mg/L PEGylated MXene concentration whereas PPGylated and bare MXene were less toxic towards normal cells, even at 500 mg/L concentration. Moreover, the toxicity was found to be directly related to the type of cell lines. In general, the HaCaT cell line exhibited the lowest toxicity while toxicity was highest in the case of the A375 cell line. The photothermal studies revealed high photo response for PEGylated MXene followed by PPGylated and bare MXenes. However, the PPGylated MXene's lower cytotoxicity towards normal cells while comparable toxicity towards malignant cells as compared to PEGylated MXenes makes the former a relatively safe and effective anticancer agent.
  16. Salmi MS, Ahmed U, Aslfattahi N, Rahman S, Hardy JG, Anwar A
    RSC Adv, 2022 Nov 15;12(51):33142-33155.
    PMID: 36425203 DOI: 10.1039/d2ra04944a
    Two dimensional (2D) nanomaterials display properties with significant biological utility (e.g., antimicrobial activity). In this study, MXene-functionalized graphene (FG) nanocomposites with Ti3C2T x in varying ratios (FG : Ti3C2T x , 25 : 75%, 50 : 50%, and 75 : 25%) were prepared and characterized via scanning electron microscopy, scanning electron microscopy-energy dispersive X-ray (SEM-EDX), high-resolution transmission electron microscopy (HRTEM), and zeta potential analysis. Their cytotoxicity was assessed using immortalized human keratinocytes (HaCaT) cells at three different timepoints, and antibacterial activity was assessed using Gram-positive Methicillin resistant Staphylococcus aureus, MRSA, and Gram-negative neuro-pathogenic Escherichia coli K1 (E. coli K1) in vitro. The nanomaterials and composites displayed potent antibacterial effects against both types of bacteria and low cytotoxicity against HaCaT cells at 200 μg mL-1, which is promising for their utilization for biomedical applications.
  17. Sam CX, Anwar AZ, Ahmad AR, Solayar GN
    Malays Orthop J, 2021 Mar;15(1):119-123.
    PMID: 33880158 DOI: 10.5704/MOJ.2103.018
    Introduction: Reverse total shoulder arthroplasty provides a surgical alternative to standard total shoulder arthroplasty for the treatment of cuff tear arthropathy, arthritis and fracture sequelae. This study aimed to assess the short-term outcomes following reverse total shoulder arthroplasty for patients in a large public hospital in Malaysia.

    Materials and Methods: We identified and performed five primary reverse total shoulder arthroplasties between 1 May 2019 and 1 June 2020. All patients were contactable and available for analysis. Assessment of functional outcomes was performed using the Constant-Murley score, the patient satisfaction score (PSS), and imaging studies. The mean follow-up from operation to the time of reporting was 9.6 months (range, 3 to 14 months).

    Results: The median age for our patients was 58 years (±11.91). The most common indication for surgery was post-traumatic arthritis, followed by rotator cuff arthropathy and osteoarthritis. The mean Constant score improved from 9.0 pre-operatively to 52.3 post-operatively at a mean of 9.6 months. The majority of the patients were satisfied with the surgery as the post-operative range of motion, especially anterior elevation and abduction, improved in four of our patients and there were no short-term complications, for example, of infection or revisions, reported at the last follow-up.

    Conclusion: This study has shown that reverse total shoulder arthroplasty can yield good short-term outcomes for the treatment of complex shoulder problems in addition to cuff tear arthropathy. It should be considered a treatment for rotator cuff tears, severe arthritis and ≥ 3 parts proximal humeral fractures.

  18. Serour G, Ghaly M, Saifuddeen SM, Anwar A, Isa NM, Chin AHB
    New Bioeth, 2023 Jun;29(2):108-120.
    PMID: 36427532 DOI: 10.1080/20502877.2022.2142094
    An exciting development in the field of assisted reproductive technologies is In Vitro Gametogenesis (IVG) that enables production of functional gametes from stem cells in the laboratory. Currently, development of this technology is still at an early stage and has demonstrated to work only in rodents. Upon critically examining the ethical dimensions of various possible IVG applications in human fertility treatment from a Sunni Islamic perspective, together with benefit-harm (maslahah-mafsadah) assessment; it is concluded that utilization of IVG, once its efficacy and safety are guaranteed, could be permissible by strictly adhering to Islamic ethical principles related to marriage, biological/genetic relatedness, sexual intercourse, and moral status of the embryo/fetus versus that of the gamete. As a result, IVG will be acceptable for treating primary infertility, age-related infertility, and preventing genetic diseases. However, it will be unacceptable for application in posthumous reproduction, donor gametes, genetic enhancement, and procreation in same-sex couples.
  19. Shahbaz MS, Anwar A, Saad SM, Kanwal, Anwar A, Khan KM, et al.
    Parasitol Res, 2020 Jul;119(7):2327-2335.
    PMID: 32476058 DOI: 10.1007/s00436-020-06710-7
    Acanthamoeba castellanii is a free-living amoeba which can cause a blinding keratitis and fatal granulomatous amoebic encephalitis. The treatment of Acanthamoeba infections is challenging due to formation of cyst. Quinazolinones are medicinally important scaffold against parasitic diseases. A library of nineteen new 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives was synthesized to evaluate their antiamoebic activity against Acanthamoeba castellanii. One-pot synthesis of 3-aryl-6,7-dimethoxyquinazolin-4(3H)-ones (1-19) was achieved by reaction of 2-amino-4,5-dimethoxybenzoic acid, trimethoxymethane, and different substituted anilines. These compounds were purified and characterized by standard chromatographic and spectroscopic techniques. Antiacanthamoebic activity of these compounds was determined by amoebicidal, encystation, excystation and host cell cytopathogenicity in vitro assays at concentrations of 50 and 100 μg/mL. The IC50 was found to be between 100 and 50 μg/mL for all the compounds except compound 5 which did not exhibit amoebicidal effects at these concentrations. Furthermore, lactate dehydrogenase assay was also performed to evaluate the in vitro cytotoxicity of these compounds against human keratinocyte (HaCaT) cells. The results revealed that eighteen out of nineteen derivatives of quinazolinones significantly decreased the viability of A. castellanii. Furthermore, eighteen out of nineteen tested compounds inhibited the encystation and excystation, as well as significantly reduced the A. castellanii-mediated cytopathogenicity against human cells. Interestingly, while tested against human normal cell line HaCaT keratinocytes, all compounds did not exhibit any overt cytotoxicity. Furthermore, a detailed structure-activity relationship is also studied to optimize the most potent hit from these synthetic compounds. This report presents several potential lead compounds belonging to 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives for drug discovery against infections caused by Acanthamoeba castellanii.
  20. Siddiqui R, Roberts SK, Ong TYY, Mungroo MR, Anwar A, Khan NA
    Parasit Vectors, 2019 Nov 14;12(1):538.
    PMID: 31727139 DOI: 10.1186/s13071-019-3785-0
    BACKGROUND: Acanthamoeba is well known to produce a blinding keratitis and serious brain infection known as encephalitis. Effective treatment is problematic, and can continue up to a year, and even then, recurrence can ensue. Partly, this is due to the capability of vegetative amoebae to convert into resistant cysts. Cysts can persist in an inactive form for decades while retaining their pathogenicity. It is not clear how Acanthamoeba cysts monitor environmental changes, and determine favourable conditions leading to their emergence as viable trophozoites.

    METHODS: The role of ion transporters in the encystation and excystation of Acanthamoeba remains unclear. Here, we investigated the role of sodium, potassium and calcium ion transporters as well as proton pump inhibitors on A. castellanii encystation and excystation and their effects on trophozoites.

    RESULTS: Remarkably 3',4'-dichlorobenzamil hydrochloride a sodium-calcium exchange inhibitor, completely abolished excystation of Acanthamoeba. Furthermore, lanthanum oxide and stevioside hydrate, both potassium transport inhibitors, resulted in the partial inhibition of Acanthamoeba excystation. Conversely, none of the ion transport inhibitors affected encystation or had any effects on Acanthamoeba trophozoites viability.

    CONCLUSIONS: The present study indicates that ion transporters are involved in sensory perception of A. castellanii suggesting their value as potential therapeutic targets to block cellular differentiation that presents a significant challenge in the successful prognosis of Acanthamoeba infections.

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