Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 284
1.
Asian J Neurosurg ; 19(1): 26-36, 2024 Mar.
Article En | MEDLINE | ID: mdl-38751389

Objective Early exposure to niche specialities, like neurosurgery, is essential to inform decisions about future training in these specialities. This study assesses the impact of a hands-on simulated aneurysm clipping workshop on medical students' and junior doctors' perceptions of neurosurgery at a student-organized neurosurgical conference. Methods Ninety-six delegates were sampled from a hands-on workshop involving hydrogel three-dimensional printed aneurysms clipping using surgical microscopes. Consultant neurosurgeons facilitated the workshop. Changes in delegates' perceptions of neurosurgery were collected using Likert scale and free-text responses postconference. Results Postworkshop, 82% of participants reported a positive impact on their perception of neurosurgery. Thematic analysis revealed that delegates valued the hands-on experience, exposure to microsurgery, and interactions with consultant neurosurgeons. Thirty-six of the 96 delegates (37.5%) expressed that the workshop dispelled preconceived fears surrounding neurosurgery and improved understanding of a neurosurgeon's day-to-day tasks. Several delegates initially apprehensive about neurosurgery were now considering it as a career. Conclusion Hands-on simulated workshops can effectively influence medical students' and junior doctors' perceptions of neurosurgery, providing valuable exposure to the specialty. By providing a valuable and immersive introduction to the specialty, these workshops can help to dispel misconceptions, fears, and apprehensions associated with neurosurgery, allowing them to consider the specialty to a greater degree than before. This study of a one-time workshop cannot effectively establish its long-term impact on said perceptions, however.

2.
Cureus ; 16(4): e58745, 2024 Apr.
Article En | MEDLINE | ID: mdl-38779274

Introduction A traumatic brain injury (TBI) is one of the leading causes of injury-related deaths, making it a public health concern of extreme importance. In a developing country such as Pakistan, TBIs are significantly underreported, with the treatment frequently being delayed and inadequate, especially in rural healthcare setups all across the country. This concern is further magnified by insufficient epidemiological data on TBIs available in Pakistan. The coronavirus disease 2019 (COVID-19) pandemic brought consequential changes to the healthcare system with the priority shifting toward COVID-19 patients, resulting in considerable changes to the workflow and management of TBIs. The primary objective of this study is to offer valuable insights into the epidemiology of TBIs in Pakistan and its relationship with the impact of the COVID-19 pandemic.  Methods A retrospective study was conducted at a tertiary care center in a metropolitan city in Pakistan. Patient charts were reviewed from January to August 2020, and data was extracted including demographics, clinical presentation, management, and outcomes for cases of TBI. Results The total number of patients is 2126, male 78% and female 21.4%. The mean age of the patients was 28.85. The state of admissions at the hospital is at 99.7% for EME admissions and 0.282% for OPD admissions. Participants presented with loss of consciousness (70.7%), nosebleeds, (53.2%), vomiting (69.0%), and seizures (11.5%). The majority (51.1%) were related to road traffic accidents, followed by falls (20.7%), and assaults (4%). While 1202 (58.5%) of these were managed conservatively, others underwent surgical treatment in the form of craniotomy (28.0%), Burr holes (3.20%), and fracture elevation and repair (10.5%). A decrease in the number of reported TBI cases was observed with lockdown implementation in Pakistan. Conclusion The transportation sector in Pakistan was severely affected by the COVID-19 pandemic, leading to a decline in road traffic injuries and TBIs. Stringent mobility constraints and changes in societal and cultural norms have contributed to this reduction.

3.
Article En | MEDLINE | ID: mdl-38787496

Thrombosis, a coagulation disorder, occurs due to altered levels of coagulation, fibrinolytic and immune factors, which are otherwise known to maintain hemostasis in normal physiological conditions. Here, we review the direct and indirect participation of a multifunctional nuclear enzyme poly (ADP-ribose) polymerase-1 (PARP1) in the expression of key genes and cellular processes involved in thrombotic pathogenesis. PARP1 biological activities range from maintenance of genomic integrity, chromatin remodeling, base excision DNA repair, stress responses to cell death, angiogenesis and cell cycle pathways. However, under homeostatic imbalances, PARP1 activities are linked with the pathogenesis of diseases, including cancer, aging, neurological disorders, and cardiovascular diseases. Disease-associated distressed cells employ a variety of PARP-1 functions such as oxidative damage exacerbations, cellular energetics and apoptosis pathways, regulation of inflammatory mediators, promotion of endothelial dysfunction, and ERK-mediated signaling in pathogenesis. Thrombosis is one such pathogenesis that comprises exacerbation of coagulation cascade due to biochemical alterations in endothelial cells, platelet activation, overexpression of adhesion molecules, cytokines release, and leukocyte adherence. Thus, the activation of endothelial and inflammatory cells in thrombosis implicates a potential role of PARP1 activation in thrombogenesis. This review article explores the direct impact of PARP1 activation in the etiology of thrombosis and discusses PARP1-mediated endothelial dysfunction, inflammation, and epigenetic regulations in the disease manifestation. Understanding PARP1 functions associated with thrombosis may elucidate novel pathogenetic mechanisms and help in better disease management through newer therapeutic interventions targeting PARP1 activity.

4.
J Neurosurg ; : 1-11, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38608302

OBJECTIVE: The objective was to evaluate the long-term outcome of microvascular decompression (MVD) utilizing autologous muscle for trigeminal neuralgia (TGN). METHODS: A retrospective review was performed of all first-time MVD patients for typical classic TGN without prior surgical intervention who were treated between 2000 and 2019 at a tertiary supraregional neurosurgery practice. Demographic characteristics, surgical findings, operative results, complications, and recurrence rates at 1 year, 5 years, and last follow-up were collected. Pain outcome was assessed using the Barrow Neurological Institute (BNI) pain score. The chi-square test with continuity correction was used to compare categorical variables, and Kaplan-Meier curves and Cox regression were used to identify factors associated with recurrence. RESULTS: In total, 1025 patients were studied with a median (interquartile range [IQR]) (range) follow-up of 8 (5-13) (3-20) years. In the immediate postoperative period, 889 patients (86.7%) had complete pain relief and 106 (10.3%) had partial pain relief; neither group required medication, and 30 patients (2.9%) had no relief. One hundred forty-one recurrences (13.8%) occurred over a median (IQR) of 3 (2-6) years after surgery. The proportion of patients without recurrence was 97% at 1 year, 90% at 5 years, 85% at 10 years, 82% at 15 years, and 81% at 20 years. There was no significant difference in the probability of recurrence between patients with complete (114/907 [12.6%] recurrences) or partial (19/106 [17.9%] recurrences) postoperative pain relief (p = 0.124, log-rank test). Patients with venous compression (n = 322) had a significantly higher rate of MVD failure (n = 16 [5%]) compared to those with arterial compression (14/703 [2%]) (p = 0.015, chi-square test). In the Cox proportional hazards model, venous compression and lack of immediate postoperative pain relief had hazard ratios of 1.62 (95% CI 1.16-2.27) and 2.65 (95% CI 1.45-4.82) for recurrence, respectively. One hundred twenty-four (12.1%) complications were documented, including facial numbness (44 [4.3%]), facial nerve palsy (37 [3.6%]), CSF leak (13 [1.3%]), and diplopia (5 [0.5%]), which resolved in all patients. CONCLUSIONS: MVD with autologous muscle provides long-lasting pain relief in TGN patients with vascular compression with minimum morbidity and is a viable alternative to synthetic materials.

5.
TH Open ; 8(1): e81-e92, 2024 Jan.
Article En | MEDLINE | ID: mdl-38313596

Inflammation and thrombosis are two distinct yet interdependent physiological processes. The inflammation results in the activation of the coagulation system that directs the immune system and its activation, resulting in the initiation of the pathophysiology of thrombosis, a process termed immune-thrombosis. Still, the shared underlying molecular mechanism related to the immune system and coagulation has not yet been explored extensively. Inspired to answer this, we carried out a comprehensive gene expression meta-analysis using publicly available datasets of four diseases, including venous thrombosis, systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. A total of 609 differentially expressed genes (DEGs) shared by all four datasets were identified based on the combined effect size approach. The pathway enrichment analysis of the DEGs showed enrichment of various epigenetic pathways such as histone-modifying enzymes, posttranslational protein modification, chromatin organization, chromatin-modifying enzymes, HATs acetylate proteins. Network-based protein-protein interaction analysis showed epigenetic enzyme coding genes dominating among the top hub genes. The miRNA-interacting partner of the top 10 hub genes was determined. The predomination of epitranscriptomics regulation opens a layout for the meta-analysis of miRNA datasets of the same four diseases. We identified 30 DEmiRs shared by these diseases. There were 9 common DEmiRs selected from the list of miRNA-interacting partners of top 10 hub genes and shared significant DEmiRs from microRNAs dataset acquisition. These common DEmiRs were found to regulate genes involved in epigenetic modulation and indicate a promising epigenetic aspect that needs to be explored for future molecular studies in the context of immunothrombosis and inflammatory disease.

7.
Cells ; 12(23)2023 11 30.
Article En | MEDLINE | ID: mdl-38067171

Mesenchymal stem/stromal cells (MSCs) are considered a valuable option to treat ocular surface disorders such as mustard keratopathy (MK). MK often leads to vision impairment due to corneal opacification and neovascularization and cellular senescence seems to have a role in its pathophysiology. Herein, we utilized intrastromal MSC injections to treat MK. Thirty-two mice were divided into four groups based on the exposure to 20 mM or 40 mM concentrations of mustard and receiving the treatment or not. Mice were clinically and histopathologically examined. Histopathological evaluations were completed after the euthanasia of mice after four months and included hematoxylin and eosin (H&E), CK12, and beta-galactosidase (ß-gal) staining. The treatment group demonstrated reduced opacity compared to the control group. While corneal neovascularization did not display significant variations between the groups, the control group did register higher numerical values. Histopathologically, reduced CK12 staining was detected in the control group. Additionally, ß-gal staining areas were notably lower in the treatment group. Although the treated groups showed lower severity of fibrosis compared to the control groups, statistical difference was not significant. In conclusion, it seems that delivery of MSCs in MK has exhibited promising therapeutic results, notably in reducing corneal opacity. Furthermore, the significant reduction in the ß-galactosidase staining area may point towards the promising anti-senescence potential of MSCs.


Mesenchymal Stem Cells , Mustard Plant , Mice , Animals , Mesenchymal Stem Cells/metabolism , Cellular Senescence/physiology , beta-Galactosidase/metabolism
9.
Ecancermedicalscience ; 17: 1606, 2023.
Article En | MEDLINE | ID: mdl-37799940

Background: Infections significantly predominate during induction chemotherapy for acute lymphoblastic leukaemia (ALL) in children. Antibacterial prophylaxis is one strategy that lowers the risk of these infections. This study evaluates the role of levofloxacin prophylaxis on the frequency of infections, febrile neutropenia (FN) and outcomes associated with it along with the development of drug-resistance. Subject and methods: This was a single-centre cohort study in which the data were collected from electronic health records between two cohorts of high-risk ALL patients in the induction phase: the first one before the initiation of levofloxacin prophylaxis and the second was after the implementation of levofloxacin prophylaxis. The variables were compared between both the groups and odds ratios were calculated for clinical outcomes. Results: Out of 227 patients, 115 were given levofloxacin prophylaxis and 112 were in the no prophylaxis group. Both cohorts were similar in demographic factors, treatment regimen and supportive care services. There was a significant difference in total in-patient admissions along with FN admissions (p = 0.026). Microbiologically documented infections and infection-related critical interventions were significantly higher in the no prophylaxis group (p < 0.05). Odds ratios with a 95% confidence interval were applied to both groups for clinical outcomes in patients with and without FN which also illustrated similar results. Overall mortality and drug resistance patterns were similar among both groups. Conclusion: This study emphasised that levofloxacin is effective in reducing inpatient admissions with FN and its complications but did not affect the drug-resistance pattern. Long-term monitoring for antibiotic resistance is mandatory.

11.
Surg Neurol Int ; 14: 350, 2023.
Article En | MEDLINE | ID: mdl-37810325

Background: Central nervous system (CNS) tuberculomas are rare and account for approximately 1% of all tuberculosis (TB) cases. These intracranial lesions are more commonly observed in immunocompromised individuals, often as part of disseminated miliary TB or after latent infection reactivation. This case report presents the occurrence of a thalamic tuberculoma in an immunocompetent girl. Case Description: An 11-year-old girl presented with a 3-month history of progressive right-sided ataxic hemiparesis, hand dystonia/thalamic hand, and headache. There was only a mildly elevated erythrocyte sedimentation rate (25 mm/h.), and her remaining biochemistry and vitals were unremarkable. Magnetic resonance imaging (MRI) brain revealed an ill-defined intra-axial heterogeneous lobulated lesion with crenated margins involving the thalamus and the posterior limb of the internal capsule with significant vasogenic edema. Given the clinical picture, the working diagnosis was a high-grade brain tumor. Due to the absence of a viable operative corridor for a meaningful resection and the diagnostic uncertainty, a stereotactic biopsy was performed, and histopathological analysis confirmed the presence of granulomas consistent with TB. A human immunodeficiency virus test (negative) and interferon-gamma release assay (positive) were then obtained. The patient was commenced on a regimen of anti-TB drugs with a tapering steroid dose. At 8 months, her most recent MRI showed a significant reduction in the size of her tuberculoma, and there is a complete resolution of her hand dystonia and hemiparesis to allow for independence in her activities of daily living. Conclusion: This report emphasizes the importance of considering causes other than degenerative, vascular, or neoplasms in patients with hemiparesis with dystonia. CNS tuberculomas can present as such without prior history or specific clinical symptoms of TB, making them a diagnostic challenge. In cases with such uncertainty regarding the nature of an intracranial lesion and the role of resection, a stereotactic biopsy is invaluable.

12.
Infect Agent Cancer ; 18(1): 51, 2023 Sep 14.
Article En | MEDLINE | ID: mdl-37710342

BACKGROUND: The role of human parvovirus B19 (B19V) infection in malignant and benign lesions such as head and neck squamous cell carcinomas (HNSCCs) and oral mucocele lesions has not been established. Herein, we examined, for the first time, the presence of B19V in HNSCCs from Iranian subjects. METHODS: One hundred and eight HNSCC specimens were analyzed for the presence of B19V using nested polymerase chain reaction (nPCR) and TaqMan quantitative PCR assays. Immunohistochemistry procedures were performed to evaluate the expression of B19V VP1/VP2 proteins, p16INK4a, and NF-κB in tumor tissues and their adjacent non-tumor tissues. In addition, 40 oral mucocele, 30 oral buccal mucosa swabs, and 30 nasopharyngeal swabs obtained from healthy adults were analyzed as controls. RESULTS: B19V DNA was detected in 36.1% of HNSCCs. Further, 23.3% of HNSCC specimens showed immunoreactivity against B19V VP1/VP2 proteins. There was a significant difference in the frequency of B19V DNA-positive cases between the patient and control groups (p < 0.0001). Moreover, comparing tumoral tissues and their adjacent non-tumor tissues in terms of immunoreactivity against B19V structural proteins, a significant association was found between tumor tissues and B19V infection (p < 0.0001). Finally, investigating the simultaneous presence of B19V and high-risk human papillomaviruses (HPV) DNA, we found a significant association between these two viral infections in HNSCCs (p = 0.031). CONCLUSIONS: To sum up, B19V was frequently present in HNSCC tissues of Iranian patients but mostly absent in the adjacent non-tumor tissues as well as oral mucocele lesions, buccal, and nasopharyngeal swabs of healthy subjects. HPV possibly contributes to B19V persistence in HNSCC tissues. Additional research is required to investigate potential etiological or cofactor roles of B19V in the development of HNSCCs.

13.
Ocul Surf ; 30: 187-195, 2023 Oct.
Article En | MEDLINE | ID: mdl-37758115

PURPOSE: Different approaches to delivery of mesenchymal stem/stromal cells (MSCs) for ameliorating corneal injuries have been investigated. This study was aimed to compare the efficacy of intrastromal and subconjunctival injection of human bone marrow-derived MSCs (hBM-MSCs) in a corneal epithelial injury model. METHODS: Twenty-four C57BL/6J mice underwent total corneal and limbal epithelial debridement. Then, the mice were divided into three different groups: (1) intrastromal hBM-MSCs injection, (2) subconjunctival hBM-MSCs injection, and (3) injection of frozen medium as a control. Mice were monitored by slit lamp and underwent anterior segment optical coherence tomography (ASOCT). Following euthanasia, the corneas were further evaluated by histology and immunostaining. RESULTS: hBM-MSC injection successfully healed epithelial defects regardless of the delivery route (P < 0.001). However, intrastromal injection was superior to subconjunctival injection in reducing defect area (P = 0.001). Intrastromal injection of hBM-MSCs also significantly reduced corneal opacity and neovascularization and improved ASOCT parameters compared to subconjunctival injection or no treatment (P < 0.001, P = 0.003, and P < 0.001, respectively). Although both of the treatment groups were positive for CK12 and had reduced levels of MUC5AC compared to the control, CK12 staining was stronger in the intrastromal group compared to the subconjunctival group. Also, persistency of MSCs was confirmed by in vivo (up to 2 weeks) and in vitro assessments (up to 4 weeks). CONCLUSIONS: Although the injection of hBM-MSC using both intrastromal and subconjunctival methods improve wound healing and reduce neovascularization and opacity, the intrastromal approach is superior in terms of corneal healing.


Corneal Injuries , Corneal Opacity , Mesenchymal Stem Cells , Humans , Mice , Animals , Mice, Inbred C57BL , Cornea/pathology , Corneal Injuries/therapy , Corneal Injuries/pathology , Disease Models, Animal
14.
Antibiotics (Basel) ; 12(9)2023 Sep 07.
Article En | MEDLINE | ID: mdl-37760712

The emergence of antibiotic resistance poses a serious threat to humankind, emphasizing the need for alternative antimicrobial agents. This study focuses on investigating the antibacterial, antibiofilm, and anti-quorum-sensing (anti-QS) activities of saponin-derived silver nanoparticles (AgNPs-S) obtained from Ajwa dates (Phoenix dactylifera L.). The design and synthesis of these novel nanoparticles were explored in the context of developing alternative strategies to combat bacterial infections. The Ajwa date saponin extract was used as a reducing and stabilizing agent to synthesize AgNPs-S, which was characterized using various analytical techniques, including UV-Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). The biosynthesized AgNPs-S exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria due to their capability to disrupt bacterial cell membranes and the leakage of nucleic acid and protein contents. The AgNPs-S effectively inhibited biofilm formation and quorum-sensing (QS) activity by interfering with QS signaling molecules, which play a pivotal role in bacterial virulence and pathogenicity. Furthermore, the AgNPs-S demonstrated significant antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and cytotoxicity against small lung cancer cells (A549 cells). Overall, the findings of the present study provide valuable insights into the potential use of these nanoparticles as alternative therapeutic agents for the design and development of novel antibiotics. Further investigations are warranted to elucidate the possible mechanism involved and safety concerns when it is used in vivo, paving the way for future therapeutic applications in combating bacterial infections and overcoming antibiotic resistance.

15.
Cureus ; 15(7): e41682, 2023 Jul.
Article En | MEDLINE | ID: mdl-37575774

Background Smartphone applications have become popular tools in clinical educational environments, particularly because they enhance learning in any setting through their accessibility. Despite students utilizing these apps in their daily learning, Pakistan's medical education system has yet to strongly endorse them. Given the rising usage of medical applications among clinical year medical students and the wide range of apps accessible on contemporary devices aimed specifically at the student population, there is a lack of literature addressing the use of these apps on clinical learning in low- and middle-income countries (LMIC) such as Pakistan. Objectives Our study aims to (1) assess the level of awareness among clinical-year medical students in Pakistan, of smartphone applications for academic purposes, (2) determine the usefulness of medical apps as educational tools for clinical-year medical students, in terms of enhancing overall patient-care skills and (3) identify barriers to the usage of apps among students who do not have them installed. Methods This online questionnaire-based study includes clinical year medical students across four medical colleges (two private and two public sectors) in Pakistan. Participant identity was kept anonymous and informed consent was required to participate. A sample size of 360 was used based on previous studies in the UK and student estimates from chosen medical colleges. The questionnaire tool used consists of three sections; demographics and medical school information, perceived usefulness of medical smartphone apps on a Likert Scale and barriers to usage among students who do not have them installed. Results 97.9% of the total study population chose to participate in the study. There was roughly an equal percentage of responses from each clinical year and 72% of students reported active use of medical apps of which the vast majority (48%) have one to two apps on their phones. Only 39% of students felt that their medical colleges encourage the use of smartphone apps for academic purposes. 54% of students use apps to look up medical criteria for disease processes and almost 42% use them to search medications. On a Likert scale of 1-5, improvement of clinical performance received highest average score among users (3.92, SD 1.1), followed by quick access to medical guidelines (3.83, SD 1.0). The most common reasons for nonuse of medical apps were medical colleges not offering subscriptions and not knowing how to utilize apps. Conclusion Smartphone apps are widely used by clinical year medical students for academic purposes in our study. Despite lack of endorsement from their respective medical colleges, these apps are still popularly utilized for revision and research on disease criteria during clinics and rounds. Encouragement from the university has been identified as a significant barrier, however. Students who use smartphone apps reported an improvement in clinical performance overall; they were able to retrieve information quicker during rounds and noticed enhancements in formulating diagnoses and reading radiological images. In contrast, those not using these apps faced challenges with interpreting imaging results, recalling pharmacological properties of medications and developing differential diagnoses. Through these findings, we highlight the benefits of incorporating technological media into the undergraduate curriculum and hope medical universities from Pakistan can take inspiration.

16.
Asian J Neurosurg ; 18(2): 404-409, 2023 Jun.
Article En | MEDLINE | ID: mdl-37397037

Cardiovascular changes following lumbar spine surgery in a prone position are exceedingly rare. Over the past 20 years, a total of six cases have been published where patients experienced varying degrees of bradycardia, hypotension, and asystole, which could be attributed to intraoperative dural manipulation. As such, there is emerging evidence for a potential neural-mediated spinal-cardiac reflex. The authors report their experience of negative chronotropy during an elective lumbar spine surgery that coincided with dural manipulation and review the available literature. A 34-year-old male presented with a long-standing history of lower back pain recently deteriorating to bilaterally radiating leg pain, with restricted left leg raise, and numbness at the left L5 dermatomal territory. The patient was an athletic police officer with no comorbidities or past medical history. Magnetic resonance imaging lumbosacral spine revealed spinal stenosis most pronounced at L4/L5 and disc bulges at L3/L4 and L5/S1. The patient opted for lumbar decompression surgery. After an unremarkable comprehensive preoperative workup, including cardiac evaluation (electrocardiogram, echocardiogram), the patient was induced general anesthesia in a prone position. A lumbar incision was made from L2 to S1. When the left L4 nerve root was retracted while removing the prolapsed disc at L4/L5, the anesthetist cautioned the surgeon of bradycardia (34 beats per minute [bpm]), and the surgery was immediately stopped. The heart rate improved to 60 bpm within 30 seconds. When the root was later retracted again, a second episode of bradycardia occurred for 4 minutes with heart rate declining to 48 bpm. The surgery was stopped, and after 4 minutes, the anesthetist administered 600 µg of atropine. The heart rate then rose to 73 bpm within 1 minute. Other potential causes for bradycardia were excluded. The total blood loss was estimated to be 100 mL. He remains well at his 6-month follow-up and has returned to work as normal. Akin to previously published cases, each episode of bradycardia coincided with dural manipulation, which may indicate a possible reflex between the spinal dura mater and the cardiovascular system. Such a rare adverse event may occur even in seemingly healthy, young individuals, and anesthetists should caution the operating surgeon of bradycardias to exclude operative manipulation of the dura as the cause. While this phenomenon is only reported in a handful of lumbar spine surgery cases, it provides evidence for a potential spinal-cardiac physiological reflex in the lumbar spine that may be neural mediated and should be investigated further.

18.
J Biochem Mol Toxicol ; 37(11): e23476, 2023 Nov.
Article En | MEDLINE | ID: mdl-37466159

Daboxin P, reported earlier from the venom of Daboia russellii, disturbs the blood coagulation cascade by targeting factor X and factor Xa. The present study exhibits that Daboxin P also inhibits platelet aggregation induced by various agonists. The thrombin-induced platelet aggregation was inhibited maximum whereas inhibition of collagen-induced platelet aggregation was found to be 50% and no inhibition of adenosine diphosphate (ADP) and arachidonic acid-induced aggregation was observed. Daboxin P dose-dependently inhibited the thrombin-induced platelet aggregation with Anti-Aggregation 50 (AD50 ) dose of 55.166 nM and also reduced the thrombin-mediated calcium influx. In-silico interaction studies suggested that Daboxin P binds to thrombin and blocks its interaction with its receptor on the platelet surface. Quenching of thrombin's emission spectrum by Daboxin P and electrophoretic profiles of pull-down assay further reveals the binding between Daboxin P and thrombin. Thus, the present study demonstrates that Daboxin P inhibits thrombin-induced platelet aggregation by binding to thrombin.


Platelet Aggregation , Thrombin , Thrombin/pharmacology , Phospholipases A2/pharmacology , Blood Coagulation , Blood Platelets , Viper Venoms/pharmacology
19.
Exp Eye Res ; 233: 109565, 2023 08.
Article En | MEDLINE | ID: mdl-37406956

Mustard agents are vesicants that were used in warfare multiple times. They are potent alkylating agents that activate cellular pathways of apoptosis, increase oxidative stress, and induce inflammation. Eyes are particularly susceptible to mustard exposure with a wide range of ocular surface damage. Three main categories of mustard-related eye injuries are acute, chronic, and delayed-onset manifestations. Mustard keratopathy (MK) is a known complication characterized by corneal opacification, ulceration, thinning, and neovascularization that can lead to severe vision loss and discomfort. Recently, a few reports demonstrated the role of senescence induction as a new pathological mechanism in mustard-related injuries that could affect wound healing. We ran the first murine model of delayed-onset MK and nitrogen mustard-induced senescence, evaluating the pathological signs of senescence in the cornea using beta-galactosidase staining. Our results suggest that nitrogen mustard exposure causes senescence in the corneal cells, which could be the underlying mechanism for chronic and late-onset ocular surface damage. We also found a significant correlation between the percentage of positive beta-galactosidase staining and the degree of fibrosis in the cornea. This provides valuable insight into the possible role of anti-senescence drugs in the near future for accelerating corneal healing and restricting fibrosis in patients with mustard keratopathy.


Chemical Warfare Agents , Corneal Diseases , Mustard Gas , Humans , Animals , Mice , Chemical Warfare Agents/toxicity , Mustard Gas/toxicity , Mechlorethamine/toxicity , Corneal Diseases/pathology , Cornea/metabolism , Cellular Senescence
20.
J Infect Dev Ctries ; 17(6): 791-799, 2023 06 30.
Article En | MEDLINE | ID: mdl-37406065

INTRODUCTION: There have been some reports of the association between SARS-CoV-2 infection and mucormycosis. This study aims to compare the hospitalization rates and clinical characteristics of mucormycosis before and during the COVID-19 pandemic. METHODOLOGY: In this retrospective study, we compared the hospitalization rate of mucormycosis patients in Namazi hospital in Southern Iran for two periods of 40 months. We defined July 1st, 2018 to February 17th, 2020, as the pre-COVID-19 period and February 18th, 2020, to September 30th, 2021, as the COVID-19 period. In addition, a quadrupled group of hospitalized patients with age and sex-matched SARS-COV-2 infection without any sign of mucormycosis was selected as the control group for COVID-associated mucormycosis. RESULT: In the total of 72 mucormycosis patients in the COVID period, 54 patients had a clinical history and a positive RT-PCR, which confirms the diagnosis of SARS-COV2 infection. The hospitalization rate of mucormycosis showed an increase of + 306% (95% CI: + 259%, + 353%) from a monthly average value of 0.26 (95% confidence interval (CI): 0.14, 0.38) in the pre-COVID period to 1.06 in the COVID period. The use of corticosteroids prior to the initiation of hospitalization (p ≤ 0.01), diabetes (DM) (p = 0.04), brain involvement (p = 0.03), orbit involvement (p = 0.04), and sphenoid sinus invasion (p ≤ 0.01) were more common in patients with mucormycosis during the COVID period. CONCLUSIONS: In high-risk patients, especially diabetics, special care to avoid the development of mucormycosis must be taken into account in patients with SARS-COV-2 infection considered for treatment with corticosteroids.


COVID-19 , Mucormycosis , Humans , COVID-19/epidemiology , Hospitalization , Mucormycosis/drug therapy , Mucormycosis/epidemiology , Pandemics , Retrospective Studies , RNA, Viral , SARS-CoV-2 , Male , Female
...