96 results on '"Alam SI"'
Search Results
2. Multimodality imaging review of ulnar nerve pathologies.
- Author
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Chaudhary RK, Karkala N, Nepal P, Gupta E, Kaur N, Batchala P, Sapire J, and Alam SI
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- Humans, Ulnar Nerve diagnostic imaging, Ulnar Nerve pathology, Wrist pathology, Ulnar Nerve Compression Syndromes diagnostic imaging, Ulnar Nerve Compression Syndromes pathology, Ulnar Neuropathies diagnostic imaging, Neoplasms
- Abstract
The ulnar nerve is the second most commonly entrapped nerve after the median nerve. Although clinical evaluation and electrodiagnostic studies remain widely used for the evaluation of ulnar neuropathy, advancements in imaging have led to increased utilization of these newer / better imaging techniques in the overall management of ulnar neuropathy. Specifically, high-resolution ultrasonography of peripheral nerves as well as MRI has become quite useful in evaluating the ulnar nerve in order to better guide treatment. The caliber and fascicular pattern identified in the normal ulnar nerves are important distinguishing features from ulnar nerve pathology. The cubital tunnel within the elbow and Guyon's canal within the wrist are important sites to evaluate with respect to ulnar nerve compression. Both acute and chronic conditions resulting in deformity, trauma as well as inflammatory conditions may predispose certain patients to ulnar neuropathy. Granulomatous diseases as well as both neurogenic and non-neurogenic tumors can also potentially result in ulnar neuropathy. Tumors around the ulnar nerve can also lead to mass effect on the nerve, particularly in tight spaces like the aforementioned canals. Although high-resolution ultrasonography is a useful modality initially, particularly as it can be helpful for dynamic evaluation, MRI remains most reliable due to its higher resolution. Newer imaging techniques like sonoelastography and microneurography, as well as nerve-specific contrast agents, are currently being investigated for their usefulness and are not routinely being used currently., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
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3. Idiopathic Chondrolysis of the Hip in Two Adolescent Females: A Six-Year Follow-Up.
- Author
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Kawas MA, Alam SI, and Hamad F
- Abstract
Idiopathic chondrolysis of the hip (ICH) is a rare condition with only a few cases reported in the literature. The average age at the onset of the disease is 11 years, with females having six times higher incidence than males. We report two cases of ICH in two medically free 10-year-old females who presented with atraumatic insidious hip pain and limping. No significant past medical, surgical, or family history was recorded. Laboratory studies were within normal limits, and the imaging showed the pathogenic changes of hip chondrolysis. Both cases were treated conservatively, and regular follow-ups in the clinic showed progressive limitation of the hip range of motion with arthritic changes on plain radiographs. Altogether, ICH is rare and can be misdiagnosed as inflammatory or infectious hip arthritis. Clinical assessment and image interpretation can lead to early diagnosis. Pain management and physical therapy with a prolonged period of protected weight-bearing are the mainstays of treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kawas et al.)
- Published
- 2023
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4. Differential phosphoproteome analysis of rat brain regions after organophosphorus compound sarin intoxication.
- Author
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Chaubey K, Alam SI, Waghmare CK, and Bhattacharya BK
- Abstract
Introduction: Sarin is a highly toxic organophosphorus nerve agent that irreversibly inhibits neuronal enzyme acetylcholinesterase. In the prevailing scenario, it is of paramount importance to develop early diagnosis and medical countermeasures for sarin exposure. A deeper understanding of the molecular mechanism of sarin intoxication and perturbations in the associated cellular processes is likely to provide valuable clues for the elucidation of diagnostic markers and therapeutic targets for sarin exposure., Methods: Present study, uncovered the changes in phosphorylation patterns of multiple proteins in different rat brain regions after sarin intoxication using 2-DE/MS approach. It provided a holistic view of the phosphorylation-mediated changes in the cellular proteome and highlighted various signaling and response pathways affected at an early time point of sarin intoxication., Results: We found total 22 proteins in the cortex, 25 proteins in the corpus striatum, and 17 proteins in the hippocampus, showed ≥1.5 fold changes (hyper- or hypo- phosphorylated) with respect to control, either at 2.5 h or 1 d after sarin exposure. These results indicated the differential expression of phosphoproteins involved in protein folding in the endoplasmic reticulum, carbon metabolism, metabolic function, and energy metabolism., Conclusion: Four candidates (protein disulfide-isomerase A3, heat shock cognate 71 kDa protein, alpha-enolase, and creatine kinase B-type), hyperphosphorylated in all three brain regions, can be further studied to understand the molecular mechanism behind neurodegenerative changes mediated by sarin exposure. The study sheds light on major pathogenic processes initiated during sarin intoxication and provides putative diagnostic markers/therapeutic targets for further validation., Competing Interests: The authors declare that they have no known competing interests or personal relationships that could have influenced the work reported in this paper., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2023
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5. Effects of heavy metals on fish physiology - A review.
- Author
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Shahjahan M, Taslima K, Rahman MS, Al-Emran M, Alam SI, and Faggio C
- Subjects
- Animals, Environmental Monitoring, Environmental Pollution, Fishes metabolism, Gills metabolism, Oxidative Stress, Metals, Heavy analysis, Water Pollutants, Chemical analysis
- Abstract
The pollution by heavy metals poses a serious threat to the aquatic environment and to the organisms if the concentration of heavy metals in the environment exceeds the safe limits. Due to their non-biodegradable and long persistence nature in the environment, heavy metals cause toxicity in fish by producing oxygen reactive species through oxidizing radical production. In this review, we investigated the effects of heavy metals on fish physiology with special emphasis on hemato-biochemical properties, immunological parameters especially hormones and enzymes, histopathology of different major organs and underlying molecular mechanisms. All those parameters are significantly affected by heavy metal exposure and are found to be important bio-monitoring tools to assess heavy metal toxicity. Hematological and biochemical alterations have been documented including cellular and nuclear abnormalities in different fish species exposed to different concentrations of heavy metals. Major fish organs (gills, liver, kidneys) including intestine, muscles showed different types of pathology specific to organs in acute and chronic exposure to different heavy metals. This study also revealed the expression of different genes involved in oxidative stress and detoxification of heavy metals. In a nutshell, this article shades light on the manipulation of fish physiology by the heavy metals and sought attention in the prevention and maintenance of aquatic environments particularly from heavy metals contaminations., (Copyright © 2022. Published by Elsevier Ltd.)
- Published
- 2022
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6. Intratendinous Ganglionic Cyst of Semimembranosus: A Rare Cause of Thigh Swelling.
- Author
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Yousaf A, Muhammad S, Zahra U, Ghaffar F, Atiq A, Elsayed N, Ghaffar MS, Yousaf S, Elsyaed AM, and Alam SI
- Abstract
Ganglionic cysts are common swellings of the hands. Various mechanisms are thought to generate these lesions, such as cystic mucoid degeneration and inflammation. Typically, ganglionic cysts are asymptomatic but can cause pain. They usually originate from soft tissues like ligaments, joint capsules, and sheaths of tendons. We present the case of a 37-year-old man with mid-thigh swelling with intermittent mild pain. However, no systemic symptoms like fever or weight loss were present. Workup unmasked the presence of a rare intratendinous ganglionic cyst. Ultrasonography (USG) and magnetic resonance imaging (MRI) can confirm the presence of ganglionic cysts and estimate their sizes and relationships with the surrounding structures. Treatment options range from observation and conservative management to interventions like aspiration and surgical excision., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Yousaf et al.)
- Published
- 2022
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7. Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO): A Case Report.
- Author
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Yousaf A, Muhammad S, Abdelazeem B, Alam SI, and Elsyaed AM
- Abstract
Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) is an uncommon adulthood disorder that presents as focal swellings and pain accompanied by abnormal changes in bone and surrounding soft tissues. X-rays of the involved region are usually insignificant; however, CT and MRI show excellent visualization of the affected structures. Typical radiological images show cortical thickening leading to decreased marrow cavity, bony erosion, and ligament ossifications. Other associated findings are synovitis and joint effusions. It is usually diagnosed on the basis of clinical as well as radiological findings. The treatment initially relies on non-steroidal anti-inflammatory drugs (NSAIDs). Patients showing poor response are started on corticosteroids and disease-modifying antirheumatic drugs (DMARDs). We report two patients who presented with joint swellings. Their workup unmasked the underlying SAPHO, which was managed well with NSAIDs., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Yousaf et al.)
- Published
- 2021
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8. 17β-Estradiol Abrogates Oxidative Stress and Neuroinflammation after Cortical Stab Wound Injury.
- Author
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Saeed K, Jo MH, Park JS, Alam SI, Khan I, Ahmad R, Khan A, Ullah R, and Kim MO
- Abstract
Disruptions in brain energy metabolism, oxidative damage, and neuroinflammation are commonly seen in traumatic brain injury (TBI). Microglial activation is the hallmark of neuroinflammation. After brain injury, microglia also act as a double-edged sword with distinctive phenotypic changes. Therefore, therapeutic applications to potentiate microglia towards pro-inflammatory response following brain injury have become the focus of attention in recent years. Here, in the current study, we investigated the hypothesis that 17β-estradiol could rescue the mouse brain against apoptotic cell death and neurodegeneration by suppressing deleterious proinflammatory response probably by abrogating metabolic stress and oxidative damage after brain injury. Male C57BL/6N mice were used to establish a cortical stab wound injury (SWI) model. Immediately after brain injury, the mice were treated with 17β-estradiol (10 mg/kg, once every day via i.p. injection) for one week. Immunoblotting and immunohistochemical analysis was performed to examine the cortical and hippocampal brain regions. For the evaluation of reactive oxygen species (ROS), reduced glutathione (GSH), and oxidized glutathione (GSSG), we used specific kits. Our findings revealed that 17β-estradiol treatment significantly alleviated SWI-induced energy dyshomeostasis and oxidative stress by increasing the activity of phospho-AMPK (Thr172) and by regulating the expression of an antioxidant gene (Nrf2) and cytoprotective enzymes (HO-1 and GSH) to mitigate ROS. Importantly, 17β-estradiol treatment downregulated gliosis and proinflammatory markers (iNOS and CD64) while significantly augmenting an anti-inflammatory response as evidenced by the robust expression of TGF-β and IGF-1 after brain injury. The treatment with 17β-estradiol also reduced inflammatory mediators (Tnf-α, IL-1β, and COX-2) in the injured mouse. Moreover, 17β-estradiol administration rescued p53-associated apoptotic cell death in the SWI model by regulating the expression of Bcl-2 family proteins (Bax and Bcl-2) and caspase-3 activation. Finally, SWI + 17β-estradiol-treated mice illustrated reduced brain lesion volume and enhanced neurotrophic effect and the expression of synaptic proteins. These findings suggest that 17β-estradiol is an effective therapy against the brain secondary injury-induced pathological cascade following trauma, although further studies may be conducted to explore the exact mechanisms.
- Published
- 2021
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9. Chronic Recurrent Multifocal Osteomyelitis and Its Management.
- Author
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Yousaf A, Muhammad S, Zoghoul SBM, Alam SI, and Elsyaed AM
- Abstract
Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory disorder of bones first reported by Giedion et al. in 1972. It is a disease of childhood, comparable to SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) in adults. CRMO presents with pain and swelling overlying the involved bones. Inflammatory markers are usually raised and X-rays usually show sclerotic lesions. MRI demonstrates the extent of the lesions accurately and associated soft tissue changes. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are the mainstays of the management. We report three patients who presented with bone pains. Extensive workup and radiological modalities along with clinical findings supported the diagnosis of CRMO. This article highlights important clinical presentations, radiological findings, and various management options., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Yousaf et al.)
- Published
- 2021
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10. Multiple Pilomatricoma in a Middle-Aged Woman.
- Author
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Muhammad S, Yousaf A, Atiq A, Munir A, and Alam SI
- Abstract
Pilomatricomas are rare skin tumors related to hair follicles. They typically present in children, and the most common locations are head and neck. Pilomatricomas are usually painless; however, they can cause cosmetic problems. Treatment is decided on an individual basis and involves local excision. However, caution should be taken if the lesion is malignant, as resection with safe margins (0.5-1.0 cm) is determinant of the overall outcome. Radiotherapy is indicated in cases of residual tumor tissue or recurrence. The role of chemotherapy in pilomatricomas is still undetermined. We report a 55-year-old female with multiple lumps on her shoulder and back. The sonographic features of these lesions were typically consistent with pilomatricomas. The patient decided to opt for excision due to cosmetic reasons and the histopathology features were suggestive of pilomatricoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Muhammad et al.)
- Published
- 2021
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11. Alpha-Linolenic Acid Impedes Cadmium-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration in Mouse Brain.
- Author
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Alam SI, Kim MW, Shah FA, Saeed K, Ullah R, and Kim MO
- Subjects
- Animals, Antioxidants pharmacology, Apoptosis, Heme Oxygenase-1 genetics, Heme Oxygenase-1 metabolism, Inflammation chemically induced, Inflammation metabolism, Inflammation pathology, JNK Mitogen-Activated Protein Kinases genetics, JNK Mitogen-Activated Protein Kinases metabolism, Male, Mice, Mice, Inbred C57BL, NF-E2-Related Factor 2 genetics, NF-E2-Related Factor 2 metabolism, NF-kappa B genetics, NF-kappa B metabolism, Neurodegenerative Diseases chemically induced, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases pathology, Cadmium toxicity, Gene Expression Regulation drug effects, Inflammation drug therapy, Neurodegenerative Diseases drug therapy, Neuroprotective Agents pharmacology, Oxidative Stress drug effects, alpha-Linolenic Acid pharmacology
- Abstract
Alpha-Linolenic acid (ALA), an omega-3 polyunsaturated fatty acid, is extracted from plant sources and has been shown to be one of the anti-inflammatory and antioxidant agents. Herein, we revealed the molecular mechanism underlying the anti-inflammatory and antioxidant potential of (ALA), against cadmium in the adult mouse brain. We evaluated the neuroprotective effect of ALA (60 mg/kg per oral for 6 weeks) against CdCl
2 (5 mg/kg)-induced oxidative stress, neuroinflammation, and neuronal apoptosis. According to our findings, ALA markedly reduced ROS production and nitric oxide synthase 2 (NOS2) and enhanced the expression of nuclear factor-2 erythroid-2 (Nrf-2) and heme oxygenase-1 (HO-1) in mice treated with CdCl2 . Most importantly, the molecular docking study revealed that ALA allosterically decreases the overexpression of c-Jun N-terminal kinase (JNK) activity and inhibited the detrimental effect against CdCl2 . Moreover, ALA suppressed CdCl2 -induced glial fibrillary acidic protein (GFAP), nuclear factor-kappa b (NF-κB), and interleukin-1β (IL-1β) in the mouse brain. Further, we also checked the pro- and anti-apoptotic proteins markers such as Bax, Bcl-2, and caspase-3, which were regulated in the cortex of ALA co-treated mouse brain. Overall, our study suggests that oral administration of ALA can impede oxidative stress, neuroinflammation, and increase neuronal apoptosis in the cortex of Cd-injected mouse brain.- Published
- 2021
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12. Imaging Findings of Subcutaneous Human Dirofilariasis.
- Author
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Alam SI, Nepal P, Lu SC, Elramadi A, and Sapire JM
- Subjects
- Animals, Dogs, Humans, Multimodal Imaging, Dirofilariasis diagnostic imaging
- Abstract
Dirofilariasis is an emerging helminthic zoonosis seldom reported. Humans are accidental hosts and rarely affected. We report a case of dirofilariasis presenting as a subcutaneous nodule in the uncommon location in the thigh with concealed history of dog meat handler. Of the cases published in literature, imaging findings of this disease have been few and far between. In this article, we describe multimodality imaging findings of dirofilariasis in the thigh., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2021
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13. Oral cancer diagnostics: An overview.
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Chaurasia A, Alam SI, and Singh N
- Abstract
Cancer was first mentioned in medicine texts by Egyptians. Ancient Indians studied oral cancer in great detail under Susruta. Cancer has continued to be a challenge to physicians from ancient times to the present. Over the years, cancer underwent a shift in management from radical surgeries toward a more preventive approach. Early diagnosis is vital in reducing cancer-associated mortality especially with oral cancer. Even though the mainstay of oral cancer diagnosis still continues to be a trained clinician and histopathologic examination of malignant tissues. Translating innovation in technological advancements in diagnostic aids for oral cancer will require both improved decision-making and a commitment toward optimizing cost, skills, turnover time between capturing data and obtaining a useful result. The present review describes the conventional to most advanced diagnostic modalities used as oral cancer diagnostics. It also includes the new technologies available and the future trends in oral cancer diagnostics., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 National Journal of Maxillofacial Surgery.)
- Published
- 2021
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14. Cadmium, an Environmental Contaminant, Exacerbates Alzheimer's Pathology in the Aged Mice's Brain.
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Ali T, Khan A, Alam SI, Ahmad S, Ikram M, Park JS, Lee HJ, and Kim MO
- Abstract
Cadmium (Cd) is an environmental contaminant, which is a potential risk factor in the progression of aging-associated neurodegenerative diseases. Herein, we have assessed the effects of chronic administration of Cd on cellular oxidative stress and its associated Alzheimer's disease (AD) pathologies in animal models. Two groups of mice were used, one group administered with saline and the other with Cd (1 mg/kg/day; intraperitoneally) for 3 months. After behavioral studies, molecular/biochemical (Immunoblotting, ELISAs, ROS, LPO, and GSH assays) and morphological analyses were performed. We observed an exacerbation of memory and synaptic deficits in chronic Cd-injected mice. Subacute and chronic Cd escalated reactive oxygen species (ROS), suppressed the master antioxidant enzymes, e.g., nuclear factor-erythroid 2-related factor 2 and heme oxygenase-1, and evoked the stress kinase phospho-c-Jun N-terminal kinase 1 signaling pathways, which may escalate AD pathologies possibly associated with amyloidogenic processes. These findings suggest the regulation of oxidative stress/ROS and its associated amyloid beta pathologies for targeting the Cd-exacerbated AD pathogenesis. In addition, these preclinical animal studies represent a paradigm for epidemiological studies of the human population exposed to chronic and subacute administration of Cd, suggesting avoiding environmental contaminants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ali, Khan, Alam, Ahmad, Ikram, Park, Lee and Kim.)
- Published
- 2021
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15. Immunoproteomic analysis of Clostridium botulinum type B secretome for identification of immunogenic proteins against botulism.
- Author
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Sharma A, Ponmariappan S, Rani S, Alam SI, and Shukla S
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- Animals, Bacterial Proteins metabolism, Botulism diagnosis, Botulism immunology, Botulism prevention & control, Clostridium botulinum classification, Clostridium botulinum immunology, Clostridium botulinum type B isolation & purification, Clostridium botulinum type B metabolism, Cross Reactions, Culture Media metabolism, Immune Sera immunology, Mice, Proteomics, Bacterial Proteins immunology, Clostridium botulinum type B immunology
- Abstract
Objectives: To identify immunogenic proteins of C. botulinum type B secretome by immunoproteomic analysis., Results: In the present study, an attempt was made to elucidate the vaccine candidates/diagnostic molecules against botulism using immuno proteomic approach. C. botulinum type B secretome was elucidated when it was grown in TPGY as well as CMM media. Predominant 51 proteins were identified in both the media using 2-DE and mass spectrometry analysis. 2D gels (CMM & TPGY) were probed with respected proteins mice antiserum and obtained 17 and 10 immunogenic proteins in TPGY as well as CMM media respectively. Hypothetical protein CLOSPO_00563, ornithine carbamoyl transferase, FlaA, molecular chaperone GroEL and secreted protease proteins were found as the common immuno dominant proteins in both media. Polyclonal Antibodies raised against C. botulinum types A and E showed cross-reactivity with secretome C. botulinum type B at the lowest dilution (1:1000) but did not show cross reactivity with highest dilution (1:30,000) with C. botulinum type B secretome. Polyclonal antibodies against C. botulinum type F secretome did not show cross reactivity with C. botulinum type B secretome., Conclusions: Identified immunogenic proteins can be used as vaccine candidates and diagnostic markers for the infant and wound botulism but common immunogenic proteins may be the best vaccine candidate molecule for development of vaccine as well as diagnostic system against the infant and wound botulism.
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- 2021
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16. Protein biomarker elucidation for the verification of biological agents in the taxonomic group of Gammaproteobacteria using tandem mass spectrometry.
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Sabna S, Kamboj DV, Rajoria S, Kumar RB, Babele P, Goel AK, Tuteja U, Gupta MK, and Alam SI
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- Biological Factors isolation & purification, Biomarkers, Gammaproteobacteria isolation & purification, Humans, Peptides chemistry, Proteins chemistry, Sensitivity and Specificity, Validation Studies as Topic, Biological Factors classification, Biological Warfare Agents classification, Gammaproteobacteria classification, Peptides analysis, Proteins analysis, Tandem Mass Spectrometry methods
- Abstract
Some pathogenic microbes can be used for nefarious applications and instigate population-based fear. In a bio-threat scenario, rapid and accurate methods to detect biological agents in a wide range of complex environmental and clinical matrices, is of paramount importance for the implementation of mitigation protocols and medical countermeasures. This study describes targeted and shot-gun tandem MS based approaches for the verification of biological agents from the environmental samples. The marker proteins and peptides were elucidated by an exhaustive literature mining, in silico analysis of prioritized proteins, and MS/MS analysis of abundant proteins from selected bacterial species. For the shot-gun methodology, tandem MS analysis of abundant peptides was carried from spiked samples. The validation experiments employing a combination of shot-gun tandem MS analysis and a targeted search reported here is a proof of concept to show the applicability of the methodology for the unambiguous verification of biological agents at sub-species level, even with limited fractionation of crude protein extracts from environmental samples.
- Published
- 2021
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17. Identification of MHC Class I bound peptides of Francisella tularensis Live Vaccine Strain using mass spectrometry.
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Gaur R, Verma DK, Alam SI, and Kamboj DV
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- Animals, Histocompatibility Antigens Class I, Humans, Mass Spectrometry, Peptides, Francisella tularensis, Tularemia prevention & control
- Abstract
Tularemia, a zoonosis generally prevalent in the northern half of the globe, is caused by Francisella tularensis. Among various Francisella tularensis species, subspecies tularensis is the most pathogenic to humans causing the infection through an airborne route, abrasions in the skin, and contact with infected animals. At present no approved vaccine exists for this intracellular pathogen. Principal defensive immunity against Francisella is T-cell mediated immunity, hence, picking out significant T-cell antigens is obligatory for Francisella vaccine advancement. In the present study, an immunoproteomics approach was employed to discover T-cell antigens by infecting dendritic cells derived from monocytes with F. tularensis NCTC10857, followed by immunoaffinity isolation of MHC class I molecules and acidic elution of bound peptides. The tandem mass spectrometry technique was used to identify the sequences of the isolated peptides. Ten MHC class I restricting Francisella derived peptides were successfully identified. Top three isolated peptide sequences were modeled and used for in silico docking study to substantiate their interaction and characterize their binding potential. Virtual docking studies further confirmed a high binding affinity for top three peptides with MHC class I molecule. The outcome of this study has led to identification of the probable vaccine candidates for human studies based on T cell-antigens against Francisella., (Copyright © 2020. Published by Elsevier B.V.)
- Published
- 2021
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18. Sonographic evaluation of leprosy of ulnar nerve.
- Author
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Zhao H, Nepal P, and Alam SI
- Abstract
Leprosy is a chronic granulomatous infection caused by Mycobacterium Leprae that predominantly affects the skin and peripheral nerves. The disease is prevalent in developing countries of Asia and Africa, with occasional cases reported from United States. In this case report we highlight a 33-year-old man from Qatar, who presented with symptoms of progressive weakness in his left wrist and hand for six months and was later found to have a granuloma of the ulnar nerve secondary to leprosy. We will discuss the etiopathogenesis, clinical features, role of imaging, and management of neuropathy due to leprosy. Our case provides an excellent learning example of the utility of ultrasonography to characterize leprosy granulomas of the ulnar nerve., (© 2021 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)
- Published
- 2021
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19. Rare presentation of chronic recurrent multifocal osteomyelitis of the Iliac wing mimicking Ewing's sarcoma.
- Author
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Nepal P, Alam SI, Sajid S, Sapire J, and Ojili V
- Abstract
This report describes a case of chronic recurrent multifocal osteomyelitis (CRMO) in an 11-year-old girl, involving the iliac bone as an initial, solitary site. Atypical imaging features were suspicious of a bone tumour, such as Ewing's sarcoma. Chronic recurrent multifocal osteomyelitis is a great masquerader and can present atypically. Radiologists should be familiar with both typical and atypical presentations, to determine an accurate diagnosis and guide appropriate management. Timely diagnosis may avoid invasive bone biopsy and inappropriate long-term antibiotic prescription for children., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this case report., (© 2021. The Authors.)
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- 2021
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20. Quinpirole-Mediated Regulation of Dopamine D2 Receptors Inhibits Glial Cell-Induced Neuroinflammation in Cortex and Striatum after Brain Injury.
- Author
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Alam SI, Jo MG, Park TJ, Ullah R, Ahmad S, Rehman SU, and Kim MO
- Abstract
Brain injury is a significant risk factor for chronic gliosis and neurodegenerative diseases. Currently, no treatment is available for neuroinflammation caused by the action of glial cells following brain injury. In this study, we investigated the quinpirole-mediated activation of dopamine D2 receptors (D2R) in a mouse model of traumatic brain injury (TBI). We also investigated the neuroprotective effects of quinpirole (a D2R agonist) against glial cell-induced neuroinflammation secondary to TBI in adult mice. After the brain injury, we injected quinpirole into the TBI mice at a dose of 1 mg/kg daily intraperitoneally for 7 days. Our results showed suppression of D2R expression and deregulation of downstream signaling molecules in ipsilateral cortex and striatum after TBI on day 7. Quinpirole administration regulated D2R expression and significantly reduced glial cell-induced neuroinflammation via the D2R/Akt/glycogen synthase kinase 3 beta (GSK3-β) signaling pathway after TBI. Quinpirole treatment concomitantly attenuated increase in glial cells, neuronal apoptosis, synaptic dysfunction, and regulated proteins associated with the blood-brain barrier, together with the recovery of lesion volume in the TBI mouse model. Additionally, our in vitro results confirmed that quinpirole reversed the microglial condition media complex-mediated deleterious effects and regulated D2R levels in HT22 cells. This study showed that quinpirole administration after TBI reduced secondary brain injury-induced glial cell activation and neuroinflammation via regulation of the D2R/Akt/GSK3-β signaling pathways. Our study suggests that quinpirole may be a safe therapeutic agent against TBI-induced neurodegeneration.
- Published
- 2021
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21. Strategy for the Enrichment of Protein Biomarkers from Diverse Bacterial Select Agents.
- Author
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Sabna S, Kamboj DV, Kumar RB, Babele P, Rajoria S, Gupta MK, and Alam SI
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- Biomarkers chemistry, Biomarkers metabolism, Humans, Bacteria chemistry, Bacteria genetics, Bacteria metabolism, Bacterial Infections genetics, Bacterial Infections metabolism, Bacterial Proteins chemistry, Bacterial Proteins genetics, Bacterial Proteins metabolism, Chaperonin 60 chemistry, Chaperonin 60 genetics, Chaperonin 60 metabolism, Phylogeny
- Abstract
Background: Some pathogenic bacteria can be potentially used for nefarious applications in the event of bioterrorism or biowarfare. Accurate identification of biological agent from clinical and diverse environmental matrices is of paramount importance for implementation of medical countermeasures and biothreat mitigation., Objective: A novel methodology is reported here for the development of a novel enrichment strategy for the generally conserved abundant bacterial proteins for an accurate downstream species identification using tandem MS analysis in biothreat scenario., Methods: Conserved regions in the common bacterial protein markers were analyzed using bioinformatic tools and stitched for a possible generic immuno-capture for an intended downstream MS/MS analysis. Phylogenetic analysis of selected proteins was carried out and synthetic constructs were generated for the expression of conserved stitched regions of 60 kDa chaperonin GroEL. Hyper-immune serum was raised against recombinant synthetic GroEL protein., Results: The conserved regions of common bacterial proteins were stitched for a possible generic immuno-capture and subsequent specific identification by tandem MS using variable regions of the molecule. Phylogenetic analysis of selected proteins was carried out and synthetic constructs were generated for the expression of conserved stitched regions of GroEL. In a proof-of-concept study, hyper-immune serum raised against recombinant synthetic GroEL protein exhibited reactivity with ~60 KDa proteins from the cell lysates of three bacterial species tested., Conclusion: The envisaged methodology can lead to the development of a novel enrichment strategy for the abundant bacterial proteins from complex environmental matrices for the downstream species identification with increased sensitivity and substantially reduce the time-to-result., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2021
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22. Vanillic Acid, a Bioactive Phenolic Compound, Counteracts LPS-Induced Neurotoxicity by Regulating c-Jun N-Terminal Kinase in Mouse Brain.
- Author
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Ullah R, Ikram M, Park TJ, Ahmad R, Saeed K, Alam SI, Rehman IU, Khan A, Khan I, Jo MG, and Kim MO
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- Animals, Brain metabolism, Brain pathology, Gliosis chemically induced, Gliosis metabolism, Gliosis pathology, JNK Mitogen-Activated Protein Kinases genetics, Male, Mice, Mice, Inbred C57BL, Brain drug effects, Gene Expression Regulation, Enzymologic drug effects, Gliosis drug therapy, JNK Mitogen-Activated Protein Kinases metabolism, Lipopolysaccharides toxicity, Neuroprotective Agents pharmacology, Vanillic Acid pharmacology
- Abstract
The receptor for advanced glycation end products (RAGE), a pattern recognition receptor signaling event, has been associated with several human illnesses, including neurodegenerative diseases, particularly in Alzheimer's disease (AD). Vanillic acid (V.A), a flavoring agent, is a benzoic acid derivative having a broad range of biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. However, the underlying molecular mechanisms of V.A in exerting neuroprotection are not well investigated. The present study aims to explore the neuroprotective effects of V.A against lipopolysaccharides (LPS)-induced neuroinflammation, amyloidogenesis, synaptic/memory dysfunction, and neurodegeneration in mice brain. Behavioral tests and biochemical and immunofluorescence assays were applied. Our results indicated increased expression of RAGE and its downstream phospho-c-Jun n-terminal kinase (p-JNK) in the LPS-alone treated group, which was significantly reduced in the V.A + LPS co-treated group. We also found that systemic administration of LPS-injection induced glial cells (microglia and astrocytes) activation and significantly increased expression level of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) and secretion of proinflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1 β (IL1-β), and cyclooxygenase (COX-2). However, V.A + LPS co-treatment significantly inhibited the LPS-induced activation of glial cells and neuroinflammatory mediators. Moreover, we also noted that V.A treatment significantly attenuated LPS-induced increases in the expression of AD markers, such as β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) and amyloid-β (Aβ). Furthermore, V.A treatment significantly reversed LPS-induced synaptic loss via enhancing the expression level of pre- and post-synaptic markers (PSD-95 and SYP), and improved memory performance in LPS-alone treated group. Taken together; we suggest that neuroprotective effects of V.A against LPS-induced neurotoxicity might be via inhibition of LPS/RAGE mediated JNK signaling pathway; and encourage future studies that V.A would be a potential neuroprotective and neurotherapeutic candidate in various neurological disorders.
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- 2020
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23. Quinovic Acid Impedes Cholesterol Dyshomeostasis, Oxidative Stress, and Neurodegeneration in an Amyloid- β -Induced Mouse Model.
- Author
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Saeed K, Shah SA, Ullah R, Alam SI, Park JS, Saleem S, Jo MH, Kim MW, Hahm JR, and Kim MO
- Subjects
- Animals, Cell Line, Tumor, Disease Models, Animal, Humans, Male, Mice, Alzheimer Disease chemically induced, Alzheimer Disease drug therapy, Alzheimer Disease metabolism, Alzheimer Disease pathology, Amyloid beta-Peptides metabolism, Amyloid beta-Peptides toxicity, Cholesterol metabolism, Oxidative Stress drug effects, Peptide Fragments metabolism, Peptide Fragments toxicity, Triterpenes pharmacology
- Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder typified by several neuropathological features including amyloid-beta (A β ) plaque and neurofibrillary tangles (NFTs). Cholesterol retention and oxidative stress (OS) are the major contributors of elevated β - and γ -secretase activities, leading to excessive A β deposition, signifying the importance of altered cholesterol homeostasis and OS in the progression of A β -mediated neurodegeneration and cognitive deficit. However, the effect of A β on cholesterol metabolism is lesser-known. In this study, we evaluated the effect of quinovic acid (QA; 50 mg/kg body weight, i.p.) against the intracerebroventricular (i.c.v.) injection of A β (1-42)-induced cholesterol dyshomeostasis, oxidative stress, and neurodegeneration in the cortex and hippocampal brain regions of wild-type male C57BL/6J mice. Our results indicated that A β (1-42)-treated mice have increased A β oligomer formation along with increased β -secretase expression. The enhanced amyloidogenic pathway in A β (1-42)-treated mice intensified brain cholesterol accumulation due to increased expressions of p53 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) enzyme. Importantly, we further confirmed the p53-mediated HMGCR axis activation by using pifithrin- α (PFT) in SH-SY5Y cells. Furthermore, the augmented brain cholesterol levels were also associated with increased OS. However, the QA administration to A β (1-42)-injected mice significantly ameliorated the A β burden, p53 expression, and cholesterol accumulation by deterring the oxidative stress through upregulating the Nrf2/HO-1 pathway. Moreover, the QA downregulated gliosis, neuroinflammatory mediators (p-NF- κ B and IL-1 β ), and the expression of mitochondrial apoptotic markers (Bax, cleaved caspase-3, and cytochrome c). QA treatment also reversed the deregulated synaptic markers (PSD-95 and synaptophysin) and improved spatial learning and memory behaviors in the A β -treated mouse brains. These results suggest that A β (1-42) induces its acute detrimental effects on cognitive functions probably by increasing brain cholesterol levels through a possible activation of the p53/HMGCR axis. However, QA treatment reduces the cholesterol-induced oxidative stress, neuroinflammation, and neurodegeneration, leading to the restoration of cognitive deficit after A β (1-42) i.c.v. injection in mice., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Kamran Saeed et al.)
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- 2020
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24. Glycine, the smallest amino acid, confers neuroprotection against D-galactose-induced neurodegeneration and memory impairment by regulating c-Jun N-terminal kinase in the mouse brain.
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Ullah R, Jo MH, Riaz M, Alam SI, Saeed K, Ali W, Rehman IU, Ikram M, and Kim MO
- Subjects
- Animals, Cell Line, Cell Survival drug effects, Cell Survival physiology, Dose-Response Relationship, Drug, Glycine pharmacology, JNK Mitogen-Activated Protein Kinases antagonists & inhibitors, Male, Maze Learning drug effects, Maze Learning physiology, Memory Disorders chemically induced, Memory Disorders prevention & control, Mice, Mice, Inbred C57BL, Neurodegenerative Diseases chemically induced, Neurodegenerative Diseases prevention & control, Neuroprotection physiology, Galactose toxicity, Glycine therapeutic use, JNK Mitogen-Activated Protein Kinases metabolism, Memory Disorders metabolism, Neurodegenerative Diseases metabolism, Neuroprotection drug effects
- Abstract
Background: Glycine is the smallest nonessential amino acid and has previously unrecognized neurotherapeutic effects. In this study, we examined the mechanism underlying the neuroprotective effect of glycine (Gly) against neuroapoptosis, neuroinflammation, synaptic dysfunction, and memory impairment resulting from D-galactose-induced elevation of reactive oxygen species (ROS) during the onset of neurodegeneration in the brains of C57BL/6N mice., Methods: After in vivo administration of D-galactose (D-gal; 100 mg/kg/day; intraperitoneally (i/p); for 60 days) alone or in combination with glycine (1 g/kg/day in saline solution; subcutaneously; for 60 days), all of the mice were sacrificed for further biochemical (ROS/lipid peroxidation (LPO) assay, Western blotting, and immunohistochemistry) after behavioral analyses. An in vitro study, in which mouse hippocampal neuronal HT22 cells were treated with or without a JNK-specific inhibitor (SP600125), and molecular docking analysis were used to confirm the underlying molecular mechanism and explore the related signaling pathway prior to molecular and histological analyses., Results: Our findings indicated that glycine (an amino acid) inhibited D-gal-induced oxidative stress and significantly upregulated the expression and immunoreactivity of antioxidant proteins (Nrf2 and HO-1) that had been suppressed in the mouse brain. Both the in vitro and in vivo results indicated that D-gal induced oxidative stress-mediated neurodegeneration primarily by upregulating phospho-c-Jun N-terminal kinase (p-JNK) levels. However, D-gal + Gly cotreatment reversed the neurotoxic effects of D-gal by downregulating p-JNK levels, which had been elevated by D-gal. We also found that Gly reversed D-gal-induced neuroapoptosis by significantly reducing the protein expression levels of proapoptotic markers (Bax, cytochrome c, cleaved caspase-3, and cleaved PARP-1) and increasing the protein expression level of the antiapoptotic protein Bcl-2. Both the molecular docking approach and the in vitro study (in which the neuronal HT22 cells were treated with or without a p-JNK-specific inhibitor (SP600125)) further verified our in vivo findings that Gly bound to the p-JNK protein and inhibited its function and the JNK-mediated apoptotic pathway in the mouse brain and HT22 cells. Moreover, the addition of Gly alleviated D-gal-mediated neuroinflammation by inhibiting gliosis via attenuation of astrocytosis (GFAP) and microgliosis (Iba-1) in addition to reducing the protein expression levels of various inflammatory cytokines (IL-1βeta and TNFα). Finally, the addition of Gly reversed D-gal-induced synaptic dysfunction by upregulating the expression of memory-related presynaptic protein markers (synaptophysin (SYP), syntaxin (Syn), and a postsynaptic density protein (PSD95)) and markedly improved behavioral measures of cognitive deficits in D-gal-treated mice., Conclusion: Our findings demonstrate that Gly-mediated deactivation of the JNK signaling pathway underlies the neuroprotective effect of Gly, which reverses D-gal-induced oxidative stress, apoptotic neurodegeneration, neuroinflammation, synaptic dysfunction, and memory impairment. Therefore, we suggest that Gly (an amino acid) is a safe and promising neurotherapeutic candidate that might be used for age-related neurodegenerative diseases.
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- 2020
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25. Lupeol, a Plant-Derived Triterpenoid, Protects Mice Brains against Aβ-Induced Oxidative Stress and Neurodegeneration.
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Ahmad R, Khan A, Lee HJ, Ur Rehman I, Khan I, Alam SI, and Kim MO
- Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that represents 60–70% of all dementia cases. AD is characterized by the formation and accumulation of amyloid-beta (Aβ) plaques, neurofibrillary tangles, and neuronal cell loss. Further accumulation of Aβ in the brain induces oxidative stress, neuroinflammation, and synaptic and memory dysfunction. In this study, we investigated the antioxidant and neuroprotective effects of the natural triterpenoid lupeol in the Aβ
1-42 mouse model of AD. An Intracerebroventricular injection (i.c.v.) of Aβ (3 µL/5 min/mouse) into the brain of a mouse increased the reactive oxygen species (ROS) levels, neuroinflammation, and memory and cognitive dysfunction. The oral administration of lupeol at a dose of 50 mg/kg for two weeks significantly decreased the oxidative stress, neuroinflammation, and memory impairments. Lupeol decreased the oxidative stress via the activation of nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) in the brain of adult mice. Moreover, lupeol treatment prevented neuroinflammation by suppressing activated glial cells and inflammatory mediators. Additionally, lupeol treatment significantly decreased the accumulation of Aβ and beta-secretase-1 (BACE-1) expression and enhanced the memory and cognitive function in the Aβ-mouse model of AD. To the best of our knowledge, this is the first study to investigate the anti-oxidative and neuroprotective effects of lupeol against Aβ1-42 -induced neurotoxicity. Our findings suggest that lupeol could serve as a novel, promising, and accessible neuroprotective agent against progressive neurodegenerative diseases such as AD.- Published
- 2020
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26. Epithelioid Hemangioendothelioma of the Ulnar Artery Presenting with Neuropathy.
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Alam SI, Nepal P, Sajid S, Al-Bozom I, Salah MM, and Muneer A
- Subjects
- Adult, Hemangioendothelioma, Epithelioid diagnostic imaging, Hemangioendothelioma, Epithelioid pathology, Hemangioendothelioma, Epithelioid surgery, Humans, Male, Treatment Outcome, Ulnar Neuropathies diagnosis, Vascular Neoplasms diagnostic imaging, Vascular Neoplasms pathology, Vascular Neoplasms surgery, Hemangioendothelioma, Epithelioid complications, Ulnar Artery diagnostic imaging, Ulnar Artery pathology, Ulnar Neuropathies etiology, Vascular Neoplasms complications
- Abstract
We present a rare case of epithelioid hemangioendothelioma arising from the wall of ulnar artery in distal forearm. The presentation was interesting in a 34-year-old man, with progressively worsening symptoms of ulnar neuropathy. A mass was seen arising from the ulnar artery on imaging with ultrasound and magnetic resonance imaging. Soft tissue epithelioid hemangioendothelioma in extremities almost always arise from the veins. Existing literature do not have elaborated imaging findings of epithelioid hemangioendothelioma arising from the arterial wall. The aim of this paper is to briefly review the interesting presentation and imaging features of this rare entity. Knowledge of such vascular tumor would avoid the mishap during surgery. Our case will add an interesting presentation of such rare pathology to the existing literature., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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27. Surface plasmon resonance sensing of Ebola virus: a biological threat.
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Sharma PK, Kumar JS, Singh VV, Biswas U, Sarkar SS, Alam SI, Dash PK, Boopathi M, Ganesan K, and Jain R
- Subjects
- Antibodies, Monoclonal chemistry, Antibodies, Monoclonal immunology, Antibody Affinity, Benzoates chemistry, Ebolavirus immunology, Hemorrhagic Fever, Ebola diagnosis, Humans, Sulfhydryl Compounds chemistry, Thermodynamics, Ebolavirus isolation & purification, Hemorrhagic Fever, Ebola virology, Surface Plasmon Resonance methods
- Abstract
Here, different monoclonal antibodies (mAb1, mAb2 and mAb3) of Ebola virus were screened in a real-time and label-free manner using surface plasmon resonance (SPR) to select an appropriate antibody for biosensor applications against a biological warfare agent. For this purpose, a gold SPR chip was modified with 4-mercaptobenzoic acid (4-MBA), and modification was confirmed by FTIR-ATR and EIS. The 4-MBA-modified gold SPR chip was used for immobilization of the recombinant nucleoprotein of Ebola (EBOV-rNP), and the interactions of mAb1, mAb2 and mAb3 were then investigated to determine the best mAb based on the affinity constant (K
D ), expressed as equilibrium dissociation constant. KD values of 809 nM, 350 pM and 52 pM were found for the interaction of mAb1, mAb2 and mAb3 of Ebola with the immobilized EBOV-rNP, respectively, thus reflecting the high affinity of mAb3. This was confirmed by ELISA results. The thermodynamic parameters (ΔG, ΔH and ΔS) for the interaction between mAb3 and EBOV-rNP were also determined, which revealed that the interaction was spontaneous, endothermic and driven by entropy. The SPR limit of detection of EBOV-rNP with mAb3 was 0.5 pg ml-1 , showing mAb3 to be the best high-affinity antibody in our study. This study has opened up new possibilities for SPR screening of different monoclonal antibodies of BWA through the convergence of materials science and optical techniques.- Published
- 2020
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28. Combination of podophyllotoxin and rutin modulate radiation-induced alterations of jejunal proteome in mice.
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Bajaj S, Alam SI, Ahmad B, Farooqi H, and Gupta ML
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- Animals, Apoptosis drug effects, Apoptosis radiation effects, Gamma Rays adverse effects, Jejunum cytology, Jejunum metabolism, Mice, Mice, Inbred C57BL, Whole-Body Irradiation, Jejunum drug effects, Jejunum radiation effects, Podophyllotoxin pharmacology, Proteome metabolism, Radiation-Protective Agents pharmacology, Rutin pharmacology
- Abstract
Purpose: Gastrointestinal (GI) injuries post ionizing radiation (IR) becomes a crucial factor in survival. Thus, the current study was aimed to explore the molecular mechanisms behind IR produced GI proteome alterations and their amelioration by a safe radioprotective formulation candidate, G-003M (podophyllotoxin+rutin). Materials and method: C57BL/6 mice were administered with G-003M 1 h before 9 Gy whole body γ irradiation. 2DE-MS analysis was conducted to identify differential expression of jejunum proteins with fold change >1.5 ( p < .05) at various time-points. Results: G-003M pre-administration decreased total number of differential proteins. It mediated protection to cytoskeleton, modulated stress, apoptosis and inflammatory proteins. Direct effect on eukaryotic translation initiation factor 4H (Eif4h), thioredoxin domain-containing protein 17 (Txndc17) and interferon-induced protein 35 (Ifi35) was observed. Bioinformatics depicted transcription factor-MYC, was also positively modulated by G-003M. Further, it also enhanced level of citrulline (ELISA analysis), and restored crypts and villi lengths (histological analysis) against severe damage caused by lethal irradiation. Conclusion: Current findings reveal that G-003M may be an efficient candidate in protecting key proteins of metabolic and biochemical pathways assisting in the rapid recovery of GI proteome. This fairly improved the chances of animal survival exposed to lethal doses of whole body radiation.
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- 2020
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29. Putative serum protein biomarkers for epsilon toxin exposure in mouse model using LC-MS/MS analysis.
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Babele P, Kumar RB, Rajoria S, Rashid F, Malakar D, Bhagyawant SS, Kamboj DV, and Alam SI
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- Animals, Chromatography, Liquid, Disease Models, Animal, Mice, Proteomics methods, Tandem Mass Spectrometry, Bacterial Toxins metabolism, Biomarkers metabolism, Blood Proteins metabolism, Clostridium perfringens metabolism
- Abstract
Epsilon toxin (ETX), produced by Clostridium perfringens Type B or type D strains, is a potential biological and toxin warfare (BTW) agent, largely for its very high toxicity. The toxin is implicated in several animal diseases. Using LC-MS/MS analysis, we report here elucidation of putative serum maker proteins for ETX exposure with an objective of the early diagnosis of intoxication. Of 166 consensus proteins (488 peptides), showing ETX-induced alterations, 119 proteins exhibited increase and 47 proteins showed decreased abundance in serum, as revealed by SWATH (DIA) acquisition on LC-MS/MS and label free quantitative analysis of control and test samples. Complement and coagulation cascade, nitrogen metabolism, negative regulation of peptidase activity, and response to ROS were among the biological processes and pathways perturbed by the ETX exposure. Interaction network indicated enzyme inhibitor activity, detoxification of ROS, and steroid binding functions were the major interaction networks for the proteins with increased abundance, while, hemostasis and structural molecule activity were the prominent networks for the down-regulated proteins. Validation studies were carried out by immunoprecipitation, ELISA, and Western blot analysis of selected proteins to demonstrate diagnostic potential of the putative marker proteins of ETX exposure., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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30. Agenesis of the piriformis muscle: A case report with review of literature.
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Nepal P, Alam SI, Sajid S, Intakhab SS, and Ojili V
- Abstract
Agenesis of the piriformis muscle is an extremely rare occurrence. Knowledge about this anatomic variant is important because of its close proximity with the sciatic nerve and sacral plexus. The piriformis muscle also serves as an important anatomic landmark for image-guided intervention and hip surgery. We report a case of piriformis muscle agenesis in a 28-year-old woman, incidentally detected on magnetic resonance imaging of the lumbosacral spine and pelvis, performed for low back pain., Competing Interests: The authors have declared that no competing interests exist., (© 2020. The Authors.)
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- 2020
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31. Elucidation of protein biomarkers for verification of selected biological warfare agents using tandem mass spectrometry.
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Rajoria S, Sabna S, Babele P, Kumar RB, Kamboj DV, Kumar S, and Alam SI
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- Biomarkers analysis, Chromatography, High Pressure Liquid, Computer Simulation, Data Mining, Peptides analysis, Bacterial Proteins analysis, Biological Warfare Agents classification, Bioterrorism prevention & control, Molecular Typing methods, Tandem Mass Spectrometry
- Abstract
Some pathogens and toxins have the potential to be used as weapons of mass destruction and instigate population-based fear. Efforts to mitigate biothreat require development of efficient countermeasures which in turn relies on fast and accurate methods to detect the biological agents in a range of complex matrices including environmental and clinical samples. We report here an mass spectrometry (MS) based methodology, employing both targeted and shot-gun approaches for the verification of biological agents from the environmental samples. Our shot-gun methodology relied on tandem MS analysis of abundant peptides from the spiked samples, whereas, the targeted method was based on an extensive elucidation of marker proteins and unique peptides resulting in the generation of an inclusion list of masses reflecting relevant peptides for the unambiguous identification of nine bacterial species [listed as priority agents of bioterrorism by Centre for Disease Control and Prevention (CDC)] belonging to phylogenetically diverse genera. The marker peptides were elucidated by extensive literature mining, in silico analysis, and tandem MS (MS/MS) analysis of abundant proteins of the cultivated bacterial species in our laboratory. A combination of shot-gun MS/MS analysis and the targeted search using a panel of unique peptides is likely to provide unambiguous verification of biological agents at sub-species level, even with limited fractionation of crude protein extracts from environmental samples. The comprehensive list of peptides reflected in the inclusion list, makes a valuable resource for the multiplex analysis of select biothreat agents and further development of targeted MS/MS assays.
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- 2020
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32. Elucidation of protein biomarkers in plasma and urine for epsilon toxin exposure in mouse model.
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Babele P, Verma S, Kumar RB, Bhagyawant SS, Kamboj DV, and Alam SI
- Subjects
- Animals, Disease Models, Animal, Electrophoresis, Gel, Two-Dimensional, Female, Mass Spectrometry, Mice, Inbred BALB C, Plasma chemistry, Urine chemistry, Bacterial Toxins toxicity, Biomarkers blood, Biomarkers urine, Poisoning pathology, Proteins analysis
- Abstract
Epsilon toxin (ETX) is the major virulence determinant of C. perfringens type B or type D strains, causing diseases in animals, besides being a listed biological and toxin warfare (BTW) agent. Keeping in mind the high lethality and the rapid onset of clinical manifestations, early diagnosis of epsilon toxin exposure is of paramount importance for implementation of appropriate medical countermeasures. Using a 2DE-MS approach, the present study is the first comprehensive proteomic elucidation of ETX-induced protein markers in the mouse model, providing putative targets for early diagnosis of ETX exposure. A total of 52 unique proteins showing ETX-induced modulations were identified in plasma and urine samples. Fibrinogen, apolipoprotein, serum amyloid protein, plasminogen, serum albumin, glutathione peroxidase, transferrin, major urinary protein 2, haptoglobin, transthyretin, and vitamin D-binding protein were among the proteins observed in more than one dataset with altered abundance after the ETX-intoxication. The predicted localization, function, and interaction of the ETX-modulated proteins in the plasma and urine indicated involvement of multiple pathways; extracellular proteins, followed by macromolecular complexes associated with blood coagulation and plasminogen activating cascade, being the most prominent among others. The putative markers elucidated here warrants further validation and can be of immense value for the early diagnosis of ETX exposure., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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33. Cardiofacial Syndrome: A Rare Case Report.
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Sunny SA, Alam SI, Adhikary AB, and Hossain MA
- Subjects
- Bangladesh, Child, Echocardiography, Female, Humans, Ductus Arteriosus, Patent, Facial Paralysis, Heart Defects, Congenital
- Abstract
Cardiofacial syndrome is associated with facial abnormality with congenital heart disease. Here, we report a case of cardiofacial syndrome having anotia and facial nerve palsy on the right side in combination with infundibular pulmonary stenosis and patent ductus arteriosus which is a rare presentation of cardiofacial syndrome. A 6 years old girl presented to department of Cardiac surgery of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh with the complaints of shortness of breath on exertion since 2 years of age. Her physical examination revealed right sided anotia and facial nerve palsy associated harsh ejection systolic murmur in upper left parasternal area. Echocardiography showed critical infundibular pulmonary stenosis with a small patent ductus arteriosus. She underwent ligation of patent ductus arteriosus and excision of infundibular muscular bands and discharged to home without any complication. Any child presented with facial abnormality should be checked for any cardiac abnormality for early intervention and better management of the patient.
- Published
- 2019
34. Development of Multispecies Recombinant Nucleoprotein-Based Indirect ELISA for High-Throughput Screening of Crimean-Congo Hemorrhagic Fever Virus-Specific Antibodies.
- Author
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Shrivastava N, Shrivastava A, Ninawe SM, Sharma S, Kumar JS, Alam SI, Kanani A, Sharma SK, and Dash PK
- Abstract
Crimean-Congo hemorrhagic fever (CCHF) is a re-emerging zoonotic viral disease prevalent in many parts of Asia, Europe, and Africa. The causative agent, Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV), is transmitted through hard ticks. Tick vectors especially belonging to the Hyalomma species serve as the reservoir and amplifying host. The vertebrate animals including sheep, goat, and bovine act as a short-lasting bridge linking the virus and ticks. CCHFV causes fatal hemorrhagic fever in humans. Humans are usually infected with CCHFV either through the bite of infected ticks or by close contact with infected animals. Immunological assays, primarily enzyme-linked immunosorbent assay (ELISA) using whole viral antigen, are widely used for serosurveillance in animals. However, the whole virus antigen poses a high biohazard risk and can only be produced in biosafety level 4 laboratories. The present study focuses on the development and evaluation of safe, sensitive, and specific IgG indirect enzyme-linked immunosorbent assay (iELISA) using recombinant nucleoprotein (NP) of CCHF virus as an antigen. The codon-optimized NP gene sequence was synthesized, cloned, and expressed in pET28a+ vector. The recombinant NP was purified to homogeneity by affinity chromatography and characterized through Western blot and MALDI-TOF/MS analysis. The characterized protein was used to develop an indirect IgG microplate ELISA using a panel of animal sera. The in-house ELISA was comparatively evaluated vis-à-vis a commercially available ELISA kit (Vector-Best, Russia) with 76 suspected samples that revealed a concordance of 90% with a sensitivity and specificity of 79.4 and 100%, respectively. The precision analysis revealed that the assay is robust and reproducible in different sets of conditions. Further, the assay was used for serosurveillance in ruminants from different regions of India that revealed 18% seropositivity in ruminants, indicating continued circulation of virus in the region. The findings suggest that the developed IgG iELISA employing recombinant NP is a safe and valuable tool for scalable high-throughput screening of CCHFV-specific antibodies in multiple species.
- Published
- 2019
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35. Neurological Enhancement Effects of Melatonin against Brain Injury-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration via AMPK/CREB Signaling.
- Author
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Rehman SU, Ikram M, Ullah N, Alam SI, Park HY, Badshah H, Choe K, and Kim MO
- Subjects
- AMP-Activated Protein Kinase Kinases, Amyloid beta-Peptides metabolism, Animals, Anti-Inflammatory Agents pharmacology, Antioxidants pharmacology, Brain drug effects, Brain metabolism, Cognition, Male, Melatonin pharmacology, Mice, Mice, Inbred C57BL, NF-kappa B metabolism, Oxidative Stress, Anti-Inflammatory Agents therapeutic use, Antioxidants therapeutic use, Brain Injuries, Traumatic drug therapy, Cyclic AMP Response Element-Binding Protein metabolism, Melatonin therapeutic use, Protein Kinases metabolism
- Abstract
Oxidative stress and energy imbalance strongly correlate in neurodegenerative diseases. Repeated concussion is becoming a serious public health issue with uncontrollable adverse effects in the human population, which involve cognitive dysfunction and even permanent disability. Here, we demonstrate that traumatic brain injury (TBI) evokes oxidative stress, disrupts brain energy homeostasis, and boosts neuroinflammation, which further contributes to neuronal degeneration and cognitive dysfunction in the mouse brain. We also demonstrate that melatonin (an anti-oxidant agent) treatment exerts neuroprotective effects, while overcoming oxidative stress and energy depletion and reducing neuroinflammation and neurodegeneration. Male C57BL/6N mice were used as a model for repetitive mild traumatic brain injury (rmTBI) and were treated with melatonin. Protein expressions were examined via Western blot analysis, immunofluorescence, and ELISA; meanwhile, behavior analysis was performed through a Morris water maze test, and Y-maze and beam-walking tests. We found elevated oxidative stress, depressed phospho-5'AMP-activated protein kinase (p-AMPK) and phospho- CAMP-response element-binding (p-CREB) levels, and elevated p-NF-κB in rmTBI mouse brains, while melatonin treatment significantly regulated p-AMPK, p-CREB, and p-NF-κB in the rmTBI mouse brain. Furthermore, rmTBI mouse brains showed a deregulated mitochondrial system, abnormal amyloidogenic pathway activation, and cognitive functions which were significantly regulated by melatonin treatment in the mice. These findings provide evidence, for the first time, that rmTBI induces brain energy imbalance and reduces neuronal cell survival, and that melatonin treatment overcomes energy depletion and protects against brain damage via the regulation of p-AMPK/p-CREB signaling pathways in the mouse brain.
- Published
- 2019
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36. Melatonin Rescue Oxidative Stress-Mediated Neuroinflammation/ Neurodegeneration and Memory Impairment in Scopolamine-Induced Amnesia Mice Model.
- Author
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Muhammad T, Ali T, Ikram M, Khan A, Alam SI, and Kim MO
- Subjects
- Amnesia psychology, Animals, Apoptosis drug effects, Brain-Derived Neurotrophic Factor metabolism, Cyclic AMP Response Element-Binding Protein metabolism, Male, Maze Learning drug effects, Mice, Mice, Inbred C57BL, Neurodegenerative Diseases chemically induced, Neurons drug effects, Neurons pathology, Reactive Oxygen Species metabolism, Synapses drug effects, Amnesia chemically induced, Amnesia prevention & control, Antioxidants pharmacology, Encephalitis prevention & control, Melatonin pharmacology, Muscarinic Antagonists, Neurodegenerative Diseases prevention & control, Oxidative Stress drug effects, Scopolamine
- Abstract
Cognitive decline and memory impairment induced by oxidative brain damage are the critical pathological hallmarks of Alzheimer's disease (AD). Based on the potential neuroprotective effects of melatonin, we here explored the possible underlying mechanisms of the protective effect of melatonin against scopolamine-induced oxidative stress-mediated c-Jun N-terminal kinase (JNK) activation, which ultimately results in synaptic dysfunction, neuroinflammation, and neurodegeneration. According to our findings, scopolamine administration resulted in LPO and ROS generation and decreased the protein levels of antioxidant proteins such as Nrf2 and HO-1; however, melatonin co-treatment mitigated the generation of oxidant factors while improving antioxidant protein levels. Similarly, melatonin ameliorated oxidative stress-mediated JNK activation, enhanced Akt/ERK/CREB signaling, promoted cell survival and proliferation, and promoted memory processes. Immunofluorescence and western blot analysis indicated that melatonin reduced activated gliosis via attenuation of Iba-1 and GFAP. We also found that scopolamine promoted neuronal loss by inducing Bax, Pro-Caspase-3, and Caspase-3 and reducing the levels of the antiapoptotic protein Bcl-2. In contrast, melatonin significantly decreased the levels of apoptotic markers and increased neuronal survival. We further found that scopolamine disrupted synaptic integrity and, conversely, that melatonin enhanced synaptic integrity as indicated by Syntaxin, PSD-95, and SNAP-23 expression levels. Furthermore, melatonin ameliorated scopolamine-induced impairments in spatial learning behavior and memory formation. On the whole, our findings revealed that melatonin attenuated scopolamine-induced synaptic dysfunction and memory impairments by ameliorating oxidative brain damage, stress kinase expression, neuroinflammation, and neurodegeneration. Graphical Abstract The proposed schematic diagram showing the neuroprotective effect of melatonin against scopolamine-induced oxidative stress-mediated synaptic dysfunction, memory impairment neuroinflammation and neurodegeneration.
- Published
- 2019
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37. Common Soft Tissue Tumors Involving the Hand with Histopathological Correlation.
- Author
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Nepal P, Songmen S, Alam SI, Gandhi D, Ghimire N, and Ojili V
- Abstract
Soft tissue tumors involving the hand are common and most often benign. It is important to know the spectrum of soft tissue tumors of the hand and understand the typical as well as atypical imaging features are seen on different imaging modalities. The imaging features are largely determined by the tumor histopathology; thus, the basic idea about the tumor histopathology will always be useful. This article intends to focus on a comprehensive approach including demographics, clinical presentation, and imaging findings required to diagnose the tumor definitely or narrow the differentials. This article discusses common soft tissue tumor mimics of the hand as well, however, excludes the bone tumors for the sake of brevity., Competing Interests: There are no conflicts of interest.
- Published
- 2019
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38. Computational Simulations Identify Pyrrolidine-2,3-Dione Derivatives as Novel Inhibitors of Cdk5/p25 Complex to Attenuate Alzheimer's Pathology.
- Author
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Zeb A, Kim D, Alam SI, Son M, Kumar R, Rampogu S, Parameswaran S, Shelake RM, Rana RM, Parate S, Kim JY, and Lee KW
- Abstract
: Mechanistically, neurotoxic insults provoke Ca
2+ -mediated calpain activation, which cleaves the cytoplasmic region of membrane-embedded p35 and produces its truncated form p25. Upon physical interaction, cyclin-dependent kinase 5 (Cdk5) and p25 forms hyperactivated Cdk5/p25 complex and causes severe neuropathological aberrations including hyperphosphorylated tau-mediated neurofibrillary tangles formation, Alzheimer's symptoms, and neuronal death. Therefore, the inhibition of Cdk5/p25 complex may relieve p-tau-mediated Alzheimer's pathology. Herein, computational simulations have identified pyrrolidine-2,3-dione derivatives as novel inhibitors of Cdk5/p25 complex. A ligand-based pharmacophore was designed and employed as 3D query to retrieve drug-like molecules from chemical databases. By molecular docking, drug-like molecules obtaining dock score > 67.67 (Goldcore of the reference compound) were identified. Molecular dynamics simulation and binding free energy calculation retrieved four pyrrolidine-2,3-dione derivatives as novel candidate inhibitors of Cdk5/p25. The root means square deviation of Cdk5/p25 in complex with candidate inhibitors obtained an average value of ~2.15 Å during the 30 ns simulation period. Molecular interactions analysis suggested that each inhibitor occupied the ATP-binding site of Cdk5/p25 and formed stable interactions. Finally, the binding free energy estimation suggested that each inhibitor had lowest binding energy than the reference compound (-113.10 kJ/mol) to recapitulate their strong binding with Cdk5/p25. Overall, these inhibitors could mitigate tau-mediated Alzheimer's phenotype.- Published
- 2019
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39. First molecular and serological evidence of Coxiella burnetti infection among sheep and goats of Jammu province of India.
- Author
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Gangoliya SR, Kumar S, Alam SI, Sharma HK, Singh M, Kotwal SK, Berri M, and Kamboj DV
- Subjects
- Animals, Antibodies, Bacterial blood, Coxiella burnetii genetics, Coxiella burnetii immunology, DNA, Bacterial analysis, Enzyme-Linked Immunosorbent Assay, Female, Goat Diseases epidemiology, Goat Diseases microbiology, Goats, India epidemiology, Milk microbiology, Molecular Diagnostic Techniques, Polymerase Chain Reaction, Prevalence, Q Fever diagnosis, Q Fever epidemiology, Serologic Tests, Serum microbiology, Sheep, Sheep Diseases epidemiology, Sheep Diseases microbiology, Vagina microbiology, Bacteriological Techniques, Coxiella burnetii isolation & purification, Goat Diseases diagnosis, Q Fever veterinary, Sheep Diseases diagnosis
- Abstract
The epidemiology and prevalence of Q fever in India is largely unknown. There are very few serologic and molecular reports of Q fever in India and these are old reports. The objective of this study was to investigate, for the first time, the presence of Coxiella burnetii infection in sheep and goat flocks of Jammu province of Jammu and Kashmir, India. A total of 148 milk (110 sheep and 38 goats) samples, 282 sera (170 sheep and 112 goats), and 152 vaginal swabs (123 sheep and 29 goats) were collected from farms with incidences of repeated abortion. The LSI Q fever ruminant serum/milk ELISA kit was used to identify anti-C. burnetii antibodies and nested PCR was employed to detect DNA in vaginal swabs. Overall, 42 (38.2%; 95% CI: 29.2-47.9) sheep and 9 (23.7%; 95% CI: 12.0-40.6) goat milk samples, and 21 (12.4%; 95% CI: 8.0-18.5) sheep and 11 (9.8%; 95% CI: 5.2-17.3) goat sera were ELISA positive. In addition, nine (7.3%; 95% CI: 3.6-13.8) vaginal swabs from sheep tested positive by nested PCR; however, C. burnetii could not be found in any of the vaginal swabs from goat. These results indicate that sheep seem to be a more important reservoir of C. burnetii than goats posing a risk for human infection in this area., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
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40. Ferulic Acid Rescues LPS-Induced Neurotoxicity via Modulation of the TLR4 Receptor in the Mouse Hippocampus.
- Author
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Rehman SU, Ali T, Alam SI, Ullah R, Zeb A, Lee KW, Rutten BPF, and Kim MO
- Subjects
- Animals, Apoptosis drug effects, Astrocytes drug effects, Astrocytes metabolism, Biomarkers metabolism, Cell Line, Cognition drug effects, Coumaric Acids pharmacology, Hippocampus drug effects, Inflammation pathology, Inflammation Mediators metabolism, JNK Mitogen-Activated Protein Kinases metabolism, Lipopolysaccharides, Male, Mice, Inbred C57BL, Microglia drug effects, Microglia metabolism, Mitochondria drug effects, Mitochondria metabolism, NF-kappa B metabolism, Nerve Degeneration pathology, Neurotoxicity Syndromes pathology, Oxidative Stress drug effects, Signal Transduction drug effects, Synapses drug effects, Synapses metabolism, Toll-Like Receptor 4 metabolism, Up-Regulation drug effects, Coumaric Acids therapeutic use, Hippocampus metabolism, Neurotoxicity Syndromes drug therapy, Neurotoxicity Syndromes metabolism
- Abstract
Microglia play a crucial role in the inflammatory brain response to infection. However, overactivation of microglia is neurotoxic. Toll-like receptor 4 (TLR4) is involved in microglial activation via lipopolysaccharide (LPS), which triggers a variety of cytotoxic pro-inflammatory markers that produce deleterious effects on neuronal cells. Ferulic acid (FA) is a phenolic compound that exerts antioxidant and anti-inflammatory effects in neurodegenerative disease. However, the manner in which FA inhibits neuroinflammation-induced neurodegeneration is poorly understood. Therefore, we investigated the anti-inflammatory effects of FA against LPS-induced neuroinflammation in the mouse brain. First, we provide evidence that FA interferes with TLR4 interaction sites, which are required for the activation of microglia-induced neuroinflammation, and further examined the potential mechanism of its neuroprotective effects in the mouse hippocampus using molecular docking simulation and immunoblot analysis. Our results indicated that FA treatment inhibited glial cell activation, p-JNK, p-NF
K B, and downstream signaling molecules, such as iNOS, COX-2, TNF-α, and IL-1β, in the mouse hippocampus and BV2 microglial cells. FA treatment strongly inhibited mitochondrial apoptotic signaling molecules, such as Bax, cytochrome C, caspase-3, and PARP-1, and reversed deregulated synaptic proteins, including PSD-95, synaptophysin, SNAP-25, and SNAP-23, and synaptic dysfunction in LPS-treated mice. These findings demonstrated that FA treatment interfered with the TLR4/MD2 complex binding site, which is crucial for evoking neuroinflammation via microglia activation and inhibited NFK B likely via a JNK-dependent mechanism, which suggests a therapeutic implication for neuroinflammation-induced neurodegeneration.- Published
- 2019
- Full Text
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41. Nicotinamide Improves Functional Recovery via Regulation of the RAGE/JNK/NF-κB Signaling Pathway after Brain Injury.
- Author
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Alam SI, Rehman SU, and Kim MO
- Abstract
Brain injuries are a serious global health issue and are the leading cause of neurodegeneration. To date, there is no proper cure and treatment for brain-injury-induced neuropathological conditions because of a lack of sufficient knowledge and the failure to develop a drug due to the multi-pathological conditions in the brain. Herein, we explored the neurotherapeutic effects of Nicotinamide (NAM), against brain injury-induced neurodegeneration and behavioral problems. Treating injured mouse brains with NAM, for 7 days, significantly ameliorated several pathological events. Interestingly, NAM treatment significantly inhibited the injury-induced activation of receptor for advanced glycation end-products (RAGE), c-Jun N-terminal kinases (JNK), and neuroinflammatory mediators, such as NF-κB, TNF-α, IL-1β, and NOS2 in the brain, and it also regulated the levels of apoptotic markers, including Bax, caspase-3, and Bcl-2. Furthermore, treatment using NAM in TBI mice, significantly reversed synaptic protein loss and improved memory impairments and behavioral outcomes. Our findings suggested that NAM treatment reduced injury-induced secondary neurodegenerative pathology by modulating RAGE/JNK/NF-κB signaling in mice. Therefore, we recommend that NAM would be a safe and efficient therapeutic agent against brain-injury-induced neurodegeneration.
- Published
- 2019
- Full Text
- View/download PDF
42. Differential proteome analysis of rat plasma after diisopropyl fluorophosphate (DFP) intoxication, a surrogate of nerve agent sarin.
- Author
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Chaubey K, Alam SI, Waghmare CK, Singh L, Srivastava N, and Bhattacharya BK
- Subjects
- Animals, Cholinesterase Inhibitors administration & dosage, Cholinesterase Inhibitors toxicity, Cholinesterases blood, Homeostasis drug effects, Injections, Subcutaneous, Iron metabolism, Isoflurophate administration & dosage, Male, Neurotoxicity Syndromes etiology, Oxidative Stress drug effects, Rats, Wistar, Reproducibility of Results, Sarin toxicity, Blood Proteins analysis, Isoflurophate toxicity, Nerve Agents toxicity
- Abstract
Diisopropyl fluorophosphate (DFP), a surrogate of nerve agent sarin, is an organophosphorus (OP) compound which inhibits neuronal enzyme acetylcholinesterase (AChE). Exposure of this compound leads to a wide range of toxic symptoms and survivors may exhibit long term neurotoxicity related to cognitive and memory defects. Due to ease of availability and similar mechanism of action to other highly toxic nerve agent, DFP is widely used as model compound to trace changes associated with nerve agent exposures. Proximal fluids are widely used for the elucidation of biomarkers for exposure to toxic substances and to study the mechanism of toxicity. Using a rat model of OP intoxication, the present study was carried out to elucidate proteomic changes in plasma associated with DFP intoxication. Rats were exposed to a single dose (0.5 LD
50 ) of DFP and their plasma proteome was studied, one day post exposure by two dimensional gel electrophoresis - mass spectrometry (2DE-MS). Some of the milestone changes were validated by Western blot analysis. A total 15 proteins showed significant fold changes in expression with respect to control after 1 day of DFP intoxication. Most of the proteins showing changes in expression at initial stages were related to immunogenic function, acute phase response, blood coagulation, and stress response. Experiments reported here demonstrate that 0.5 LD50 DFP intoxication leads to AChE inhibition, modulation of immunogenic function, and generation of stress at an early stage. Although, some proteins and their putative functional ramifications indicated similarity with those observed in our previous plasma proteome study, neurodegenerative changes were not observed in plasma of 0.5 LD50 DFP treated animals., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2019
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43. Neuroprotective Effect of Quercetin Against the Detrimental Effects of LPS in the Adult Mouse Brain.
- Author
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Khan A, Ali T, Rehman SU, Khan MS, Alam SI, Ikram M, Muhammad T, Saeed K, Badshah H, and Kim MO
- Abstract
Chronic neuroinflammation is responsible for multiple neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Lipopolysaccharide (LPS) is an essential component of the gram-negative bacterial cell wall and acts as a potent stimulator of neuroinflammation that mediates neurodegeneration. Quercetin is a natural flavonoid that is abundantly found in fruits and vegetables and has been shown to possess multiple forms of desirable biological activity including anti-inflammatory and antioxidant properties. This study aimed to evaluate the neuroprotective effect of quercetin against the detrimental effects of LPS, such as neuroinflammation-mediated neurodegeneration and synaptic/memory dysfunction, in adult mice. LPS [0.25 mg/kg/day, intraperitoneally (I.P.) injections for 1 week]-induced glial activation causes the secretion of cytokines/chemokines and other inflammatory mediators, which further activate the mitochondrial apoptotic pathway and neuronal degeneration. Compared to LPS alone, quercetin (30 mg/kg/day, I.P.) for 2 weeks (1 week prior to the LPS and 1 week cotreated with LPS) significantly reduced activated gliosis and various inflammatory markers and prevented neuroinflammation in the cortex and hippocampus of adult mice. Furthermore, quercetin rescued the mitochondrial apoptotic pathway and neuronal degeneration by regulating Bax/Bcl2, and decreasing activated cytochrome c, caspase-3 activity and cleaving PARP-1 in the cortical and hippocampal regions of the mouse brain. The quercetin treatment significantly reversed the LPS-induced synaptic loss in the cortex and hippocampus of the adult mouse brain and improved the memory performance of the LPS-treated mice. In summary, our results demonstrate that natural flavonoids such as quercetin can be beneficial against LPS-induced neurotoxicity in adult mice.
- Published
- 2018
- Full Text
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44. Identification of Proteins Differentially Expressed in the Striatum by Melatonin in a Middle Cerebral Artery Occlusion Rat Model-a Proteomic and in silico Approach.
- Author
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Shah FA, Zeb A, Ali T, Muhammad T, Faheem M, Alam SI, Saeed K, Koh PO, Lee KW, and Kim MO
- Abstract
Ischemic stroke is characterized by permanent or transient obstruction of blood flow, which initiates a cascading pathological process, starting from acute ATP loss to subsequent membrane depolarization, glutamate excitotoxicity, and calcium overload. Melatonin is a potent antioxidant that exerts protective effects in different experimental stroke models. In this study, melatonin effects were demonstrated by a proteomic and in silico approach. The proteomic study identified differentially expressed proteins by 2D gel electrophoresis in the striatum 24 h after middle cerebral artery occlusion. Proteomic analysis revealed several proteins with aberrant expression and was validated by western blot and immunofluorescence analysis. Homology modeling was performed to build 3D structures for γ-enolase, thioredoxin (TRX), and heat shock 60 (HSP60) by the template crystal structures using a protein data bank as a sequence database. The structure refinement of each model was achieved by energy minimization via molecular dynamic simulation, and the generated models were further assessed for stability by Procheck and ProSA. The models were processed for docking analysis using AutoDock Vina, and post-docking analysis was determined by discovery studio. The proteomic study showed decreased expression of γ-enolase, TRX, and protein phosphatase 2A subunit B and increased expression of collapsin response mediator protein 2 and HSP60 in the striatum after ischemic injury. Treatment with melatonin modulated the expression profiles of these proteins. This study demonstrated the neuroprotective role of melatonin in the ischemic striatum using a proteomic and in silico approach. Collectively, melatonin may act in a multimechanistic way by modulating the expression of several proteins in the ischemic striatum.
- Published
- 2018
- Full Text
- View/download PDF
45. Experimental Treatment of a Suspected Case of Mycetoma Based on Dot-in-Circle Sign.
- Author
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Nepal P MD, Alam SI MD, Adhikari N MBBS, Ghimire N MDS, Ojili V MD, and Yousefi A MD
- Abstract
Competing Interests: Conflict of Interest: None declared.
- Published
- 2018
46. Investigation of non-hydroxamate scaffolds against HDAC6 inhibition: A pharmacophore modeling, molecular docking, and molecular dynamics simulation approach.
- Author
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Zeb A, Park C, Son M, Rampogu S, Alam SI, Park SJ, and Lee KW
- Subjects
- Binding Sites, Catalytic Domain, Computer Simulation, Databases, Chemical, Drug Design, Histone Deacetylase 6 chemistry, Histone Deacetylase 6 metabolism, Humans, Hydrogen Bonding, Hydroxamic Acids chemistry, Molecular Docking Simulation, Molecular Dynamics Simulation, Reproducibility of Results, Drug Evaluation, Preclinical methods, Histone Deacetylase 6 antagonists & inhibitors, Histone Deacetylase Inhibitors chemistry, Histone Deacetylase Inhibitors pharmacology, Quantitative Structure-Activity Relationship
- Abstract
Proteins deacetylation by Histone deacetylase 6 (HDAC6) has been shown in various human chronic diseases like neurodegenerative diseases and cancer, and hence is an important therapeutic target. Since, the existing inhibitors have hydroxamate group, and are not HDAC6-selective, therefore, this study has designed to investigate non-hydroxamate HDAC6 inhibitors. Ligand-based pharmacophore was generated from 26 training set compounds of HDAC6 inhibitors. The statistical parameters of pharmacophore (Hypo1) included lowest total cost of 115.63, highest cost difference of 135.00, lowest RMSD of 0.70 and the highest correlation of 0.98. The pharmacophore was validated by Fischer's Randomization and Test Set validation, and used as screening tool for chemical databases. The screened compounds were filtered by fit value ([Formula: see text]), estimated Inhibitory Concentration (IC[Formula: see text]) ([Formula: see text]), Lipinski's Rule of Five and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) Descriptors to identify drug-like compounds. Furthermore, the drug-like compounds were docked into the active site of HDAC6. The best docked compounds were selected having goldfitness score [Formula: see text] and [Formula: see text], and hydrogen bond interaction with catalytic active residues. Finally, three inhibitors having sulfamoyl group were selected by Molecular Dynamic (MD) simulation, which showed stable root mean square deviation (RMSD) (1.6-1.9[Formula: see text]Å), lowest potential energy ([Formula: see text][Formula: see text]kJ/mol), and hydrogen bonding with catalytic active residues of HDAC6.
- Published
- 2018
- Full Text
- View/download PDF
47. Identification of Cross Reactive Antigens of C. botulinum Types A, B, E & F by Immunoproteomic Approach.
- Author
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Sharma A, Ponmariappan S, Sarita R, Alam SI, Kamboj DV, and Shukla S
- Subjects
- Animals, Bacterial Proteins chemistry, Bacterial Proteins immunology, Botulinum Toxins immunology, Botulism immunology, Clostridium botulinum genetics, Clostridium botulinum immunology, Electrophoresis, Gel, Two-Dimensional, Enzyme-Linked Immunosorbent Assay, Humans, Mice, Mice, Inbred BALB C, Botulinum Toxins chemistry, Botulism microbiology, Clostridium botulinum chemistry
- Abstract
Diseases triggered by microorganisms can be controlled by vaccines, which need neutralizing antigens. Hence, it is very crucial to identify extremely efficient immunogens for immune prevention. Botulism, a fatal neuroparalytic disease, is caused by botulinum neurotoxins produced by the anaerobic, Gram-positive spore-forming bacteria, Clostridium botulinum. Food-borne botulism and iatrogenic botulism are caused by botulinum toxin. Wound botulism, infant botulism, and adult intestinal botulism are caused by primarily C. botulinum followed by secondary intoxication. To identify protective antigens, whole cell proteome of C. botulinum type B was separated by two-dimensional gel electrophoresis. 2-D gel of whole cell proteins was probed with hyper immune sera of whole cell proteins of C. botulinum types A, E, and F. Six cross immunoreactive proteins were identified. These immunoreactive proteins will be further tested for developing vaccines and serodiagnostic markers against botulism.
- Published
- 2018
- Full Text
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48. Distribution Pattern and Outcome of the Patients in the Intensive Care Unit of Bangabandhu Sheikh Mujib Medical University: A Short Term Analysis.
- Author
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Alam SI, Hossain MA, Aftabuddin M, Hye MA, and Mondal MK
- Subjects
- Adult, Aged, Bangladesh, Humans, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Universities, Hospital Mortality, Intensive Care Units, Length of Stay
- Abstract
The aim of the study was to describe the characteristics of patients admitted to intensive care unit and their outcome in Bangabandhu Sheikh Mujib Medical University, Bangladesh. This retrospective, descriptive study was conducted in the intensive care unit of Bangabandhu Sheikh Mujib Medical University (BSMMU) from January 2016 to June 2016. Data was retrieved from hospital records of all admitted patients regarding age, gender, admission source, reason for admission, length of ICU stay, requirement of mechanical ventilation, number of organ failure and their outcome. During this study period, the total number of patients admitted was 225; most of them were males (148, 65.7%). Among the 225 patients, the highest number of admission was comprised of intracranial haemorrhage (22.6%), followed by sepsis (12.4%), acute respiratory distress syndrome (10.2%), acute renal failure (9.3%) malignancy (8.8%) and ischemic stroke (8.0%). Mean age of the patient was 54±18 years and mean length of ICU stay was 6.8±3 days. Out of 225 patients, 87 expired (38.6%). Majority of the patients required mechanical ventilation (69.3%) and had multi organ failure (59.8%). Most of the expiries were due to intracranial haemorrhage (24.1%); followed by acute respiratory distress syndrome (12.6%), malignancy (12.6%) and sepsis (11.4%). Elderly age (>65 years), requirement of mechanical ventilation and multiorgan failure had significant relationship (p<0.05) with overall ICU mortality. Intracranial haemorrhage, sepsis, acute respiratory distress syndrome were the main reasons for admissions in ICU, while mortality was highest for intracranial haemorrhage. Developing a well equipped neurological ICU with adequately trained staff will help to improve the outcome of patients.
- Published
- 2018
49. From the Cover: Proteome Profile of Different Rat Brain Regions After Sarin Intoxication.
- Author
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Chaubey K, Alam SI, Nagar DP, Waghmare CK, Pant SC, Singh L, Srivastava N, and Bhattacharya BK
- Subjects
- Acetylcholinesterase metabolism, Animals, Blotting, Western, Brain metabolism, Brain pathology, Electrophoresis, Gel, Two-Dimensional, GPI-Linked Proteins antagonists & inhibitors, GPI-Linked Proteins metabolism, Lethal Dose 50, Male, Nerve Degeneration, Neurotoxicity Syndromes metabolism, Neurotoxicity Syndromes pathology, Protein Interaction Maps, Proteomics methods, Rats, Wistar, Reproducibility of Results, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tandem Mass Spectrometry, Time Factors, Brain drug effects, Chemical Warfare Agents toxicity, Cholinesterase Inhibitors toxicity, Nerve Tissue Proteins metabolism, Neurotoxicity Syndromes etiology, Proteome, Sarin toxicity
- Abstract
Sarin is an organophosphorus (OP) chemical warfare agent which irreversibly inhibits acetylcholinesterase. Acute toxicity after sarin exposure is because of hyper activation of the nicotinic and muscarinic receptor. Survivors of sarin exposure often develop long-term neuropathology referred as OP ester-induced chronic neurotoxicity. However, the exact mechanism of chronic neurotoxicity is yet unknown. We studied proteomic changes in rat brain regions after 0.5 LD50 dose of sarin and investigated some milestone changes associated with long-term CNS injury. We used two-dimensional gel electrophoresis/mass spectrometry approach to identify early proteomic changes and traced expression of selected proteins for longer time points. This study shows changes in chaperone function, endoplasmic reticulum stress, and defect in cytoskeleton functions at earlier stages. Predictive interaction analysis demonstrated putative role of Parkinson's disease-related proteins after sarin exposure. Our results clearly indicated neurodegenerative changes which started after 2.5 h and showed prominence after 3-month postexposure. The study also unmasks changes in proteins related to movement and cognitive function. The markers for astrocytosis (GFAP) and neurodegenerative changes (alpha-synuclein and amyloid precursor protein) exhibited altered expression in brain. This is the first proteomic study among survivors of sarin exposure in animal model. Some of the early changes, including those involved in neurodegeneration, movement, and cognitive function, defects in chaperone function and cytoskeleton, were shown to persist for a longer period. The study provides a preliminary framework for further validation of major mechanisms of sarin toxicity is suggested here and opens new avenues for elucidation of therapeutic intervention., (© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology.All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2017
- Full Text
- View/download PDF
50. Intramuscular Diclofenac Vs Periprostatic Lidocaine Injection For Controlling Pain Undergoing Transrectal Ultrasound Guided Prostatic Biopsy.
- Author
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Alam SI, Hazratullah, Kibria Z, Masood I, and Jawed R
- Subjects
- Aged, Anesthetics, Local administration & dosage, Cyclooxygenase Inhibitors administration & dosage, Humans, Injections, Male, Middle Aged, Pain diagnosis, Rectum, Diclofenac administration & dosage, Endosonography methods, Image-Guided Biopsy methods, Lidocaine administration & dosage, Pain drug therapy, Pain Measurement methods, Prostatic Neoplasms pathology
- Abstract
Background: Transrectal ultrasound (TRUS) technique for getting prostatic tissue for histopathology is now the standard procedure for malignant lesions of the prostate and imperative diagnostic investigation of patients with clinical specks of prostatic neoplasia. During TRUS guided biopsy, pain control has been important issue therefore, highly potent analgesia before this procedure should be considered on high priority according to current census. Therefore, we compared intramuscular diclofenac injection with sensory blockade of injection lidocaine to abolish pain undergoing prostatic biopsy with TRUS technique., Methods: Total 200 patients were selected for this study having raised PSA values and suspicious nodule on Digital Rectal Examination. These patients were segregated into two groups by randomization. Group "A" received intramuscular diclofenac and group "B" were infiltrated with lidocaine injection for sensory blockade., Results: Patients in group A was having mean age of 64.5±5.8 years while for group B patients was 65.6±4.9 years (p=0.16). Both groups have statistically insignificant difference in their mean PSA values (p=0.24) and mean prostatic volume (p=0.22). The mean pain scores on visual analogue scale in groups A was 3.5±0.8 and in group B it was 2.4±0.8 (p<0.001). 60% group A patients reported with mild or no pain compared to 90% in group B. (p<0.001).., Conclusions: Local blockade with lidocaine injection has better pain control as compared to patients experienced pain with intramuscular diclofenac used for prostatic biopsy through TRUS technique..
- Published
- 2017
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