Publications by authors named "Komal Naeem"

17 Publications

  • Page 1 of 1

Role of redundant nerve roots in clinical manifestations of lumbar spine stenosis.

Surg Neurol Int 2021 10;12:218. Epub 2021 May 10.

Department of Neurosurgery, Aga Khan University, Karachi, Sindh, Pakistan.

Background: Redundant nerve roots (RNRs) are defined as elongated, thickened, and tortious appearing roots of the cauda equina secondary to lumbar spinal canal stenosis (LSCS). The study compared the clinical and radiological features of patients with LSCS with versus without RNR.

Methods: This retrospective study was performed on 55 patients who underwent decompressive surgery for degenerative LSCS. Patients were divided into two groups based on the presence of RNR in their preoperative magnetic resonance imaging, as evaluated by a radiologist blinded to the study design. Medical records were reviewed for basic demographic, clinical MR presentation, and outcomes utilizing Japanese Orthopaedic Association (JOA) scores.

Results: The mean age of enrolled patients was 57.1, with mean follow-up of 4.0 months. RNR was found in 22 (40%) of patients with LSCS. These patients were older than those patients without RNR (62.2 vs. 53.7). Interestingly, there were no statistically significant differences in clinical presentations, duration of symptoms, and outcomes using JOA scores between the two groups.

Conclusion: RNR is a relatively common radiological finding (i.e., 40%) in patients with LSCS. It is more likely to be observed in older patients. However, no significant differences were noted in clinical presentation and functional outcomes with respect to the presence or absence of RNR.
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http://dx.doi.org/10.25259/SNI_59_2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168691PMC
May 2021

Enhanced Accumulation of Cisplatin in Ovarian Cancer Cells from Combination with Wedelolactone and Resulting Inhibition of Multiple Epigenetic Drivers.

Drug Des Devel Ther 2021 25;15:2211-2227. Epub 2021 May 25.

Eman Research Journal, Eman Research, Sydney, NSW, Australia.

Purpose: Cisplatin resistance is a major concern in ovarian cancer treatment. The aim of this study was to investigate if wedelolactone could perform better in resistant ovarian cancer cells when used in combination with cisplatin.

Methods: Growth inhibitory potential of wedelolactone and cisplatin was investigated through MTT reduction assay in ovarian cancer cell lines including A2780 (sensitive), A2780 (cisplatin resistant) and A2780 Resistance factor (RF) of drugs was determined in these three cell lines. Combination index (CI) was calculated as a measure of combined drug action. Effect of this combination on changes in the cellular accumulation of platinum levels and platinum-DNA binding was also determined using AutoDock Vina while the effect of wedelolactone on inhibition of possible key culprits of resistance including Chk1, CD73, AT tip60, Nrf2, Brd1, PCAF, IGF1, mTOR1 and HIF2α was investigated .

Results: Cisplatin and wedelolactone showed a dose-dependent growth inhibitory effect. RF value of wedelolactone was 1.1 in the case of A2780 showing its potential to bring more cell death in cisplatin-resistant cells. CI values were found to vary showing antagonistic to additive outcomes. Additive effect was observed for all sequences of administration (0/0, 0/4 and 4/0 h) in A2780. Enhanced cellular accumulation of cisplatin was observed in parent and resistant cells on combination. Docking results revealed that among the selected oncotargets, Chk1, CD73, Nrf2, PCAF and AT tip60 were more vulnerable to wedelolactone than their respective standard inhibitors.

Conclusion: These findings have shown that additive outcome of drug combination in A2780 and raised levels of platinum accumulation followed a clear pattern. This observation indicates that the presence of wedelolactone might have contributed to sensitize A2780. However, results point to the possible effects of this compound on epigenetic factors involving tumor microenvironment, epithelial mesenchymal transition, and immune-checkpoint kinases.
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http://dx.doi.org/10.2147/DDDT.S288707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164677PMC
May 2021

Comparison of Surgical Outcomes and Recurrence Rates of Cystic and Solid Vestibular Schwannomas.

J Neurol Surg B Skull Base 2021 Jun 21;82(3):333-337. Epub 2019 Oct 21.

Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, United States.

 Cystic vestibular schwannomas (CVSs) are anecdotally believed to have worse clinical and tumor-control outcomes than solid vestibular schwannomas (SVSs); however, no data have been reported to support this belief. In this study, we characterize the clinical outcomes of patients with CVSs versus those with SVSs.  This is a retrospective review of prospectively collected data.  This study is set at single high-volume neurosurgical institute.  We queried a database for details on all patients diagnosed with vestibular schwannomas between January 2009 and January 2014.  Records were retrospectively reviewed and analyzed using univariate and multivariate analyses to study the differences in clinical outcomes and tumor progression or recurrence.  Of a total of 112 tumors, 24% (  = 27) were CVSs and 76% (  = 85) were SVSs. Univariate analysis identified the extent of resection, Koos grade, and tumor diameter as significant predictors of recurrence (  ≤ 0.005). However, tumor diameter was the only significant predictor of recurrence in the multivariate analysis (  = 0.007). Cystic change was not a predictor of recurrence in the univariate or multivariate analysis (  ≥ 0.40). Postoperative facial nerve and hearing outcomes were similar for both CVSs and SVSs (  ≥ 0.47).  Postoperative facial nerve outcome, hearing, tumor progression, and recurrence are similar for patients with CVSs and SVSs. As CVS growth patterns and responses to radiation are unpredictable, we favor microsurgical resection over radiosurgery as the initial treatment. Our data do not support the commonly held belief that cystic tumors behave more aggressively than solid tumors or are associated with increased postoperative facial nerve deficits.
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http://dx.doi.org/10.1055/s-0039-1697039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133812PMC
June 2021

Prone Single-Position Lateral Lumbar Interbody Fusion With Posterior Decompression and Pedicle Screw Fixation for the Treatment of Grade II Spondylolisthesis: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2021 Apr 30. Epub 2021 Apr 30.

Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.

Lateral lumbar interbody fusion (LLIF) provides indirect decompression without disruption of the posterior elements. It involves a larger implant footprint than that of posterior approaches. LLIF is typically performed with the patient in the lateral decubitus position. When a posterior fixation is indicated, a second-stage procedure is performed with the patient in the prone position. Single-position surgery provides the potential advantage of decreased operative time because both procedures can be performed without patient repositioning. Single-position LLIF and posterior fixation in the prone position have not been well validated to date. Herein, techniques for LLIF, percutaneous pedicle screw fixation, and facetectomy in the prone position are shown. A 76-yr-old woman with osteoporosis presented with severe back and bilateral leg pain refractory to conservative management and imaging findings of grade 2 dynamic anterolisthesis at L4-L5 with severe stenosis. She underwent LLIF with percutaneous pedicle screw fixation and facetectomy. She was placed on a Jackson table in the prone position for the entire procedure, which was performed in a single stage. Percutaneous pedicle screws were placed, followed by a left-sided minimally invasive facetectomy. A left-sided retroperitoneal transpsoas approach was used to perform the LLIF in standard fashion. Finally, the rods were locked into place. Postoperatively, the patient was neurologically stable, and imaging confirmed good hardware placement. At the 6-wk follow-up, the patient was doing well. This case demonstrates the feasibility of performing LLIF and posterior fixation in a single stage in the prone position. The patient provided informed consent. Used with permission from Barrow Neurological Institute.
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http://dx.doi.org/10.1093/ons/opab107DOI Listing
April 2021

Enhanced neuroprotective and antidepressant activity of curcumin-loaded nanostructured lipid carriers in lipopolysaccharide-induced depression and anxiety rat model.

Int J Pharm 2021 Jun 5;603:120670. Epub 2021 May 5.

Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan. Electronic address:

The present study aims to develop curcumin-loaded nanostructured lipid carriers (CUR-NLCs) and investigate their neuroprotective effects in lipopolysaccharide (LPS)-induced depression and anxiety model. Nanotemplate engineering technique was used to prepare CUR-NLCs with Compritol 888 ATO and oleic acid as solid and liquid lipid, respectively. Poloxamer 188, Tween 80 and Span 80 were used as stabilizing agents for solid-liquid lipid core. The physicochemical parameters of CUR-NLCs were determined followed by in vitro drug release and in vivo neuroprotective activity in rats. The optimized CUR-NLCs demonstrated nanometric particle size of 147.8 nm, surface charge of -32.8 mV and incorporation efficiency of 91.0%. CUR-NLCs showed initial rapid followed by a sustained drug release reaching up to 73% after 24 h. CUR-NLCs significantly elevated struggling time and decreased immobility time in forced swim and tail suspension tests. A substantial increase in time spent and number of entries into the light and open compartments was observed in light-dark box and elevated plus maze models. CUR-NLCs improved the tissue architecture and suppressed the expression of p-NF-κB, TNF-α and COX-2 in brain tissues from histological and immunohistochemical analysis. CUR-NLCs improved the neuroprotective effect of curcumin and can be used as a potential therapeutics for depression and anxiety.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120670DOI Listing
June 2021

Contribution of Attenuation of TNF-α and NF-κB in the Anti-Epileptic, Anti-Apoptotic and Neuroprotective Potential of Fruit and Its Chitosan Encapsulation.

Molecules 2021 Apr 17;26(8). Epub 2021 Apr 17.

Departament of Pharmacognosy, Riphah Institute of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan.

L. (Rosaceae) is one of the least reported and most understudied members of this family. It is native to the Himalayan regions of Pakistan and Nepal. The anti-convulsant effect of -hexane extract of fruit of was investigated in a pentylenetetrazole (PTZ)-induced animal model of epilepsy. Male Sprague-Dawley rats were divided into six groups (n = 7) including control, PTZ (40 mg/kg), diazepam (4 mg/kg) and -hexane extract (at 50, 150 and 300 mg/kg). Convulsive behavior was observed and resultant seizures were scored, animals sacrificed and their brains preserved. Chitosan nanoparticles were prepared using the ionic gelation method and characterized by UV-analysis, zeta potential and Fourier transform infrared spectroscopy (FTIR). The effects of all the treatments on the expression of phosphorylated cytokine tumor necrosis factor α (p-TNF-α) and phosphorylated transcription factor nuclear factor kappa B (p-NF-κB) expression in the cortex and hippocampus of the brains of treated rats were studied through enzyme linked immunosorbent assay (ELISA) and morphological differences and surviving neuronal number were recorded through hematoxylene and eosin (H&E) staining. Significant changes in seizures score and survival rate of rats were observed. Downregulation of neuro-inflammation, p-TNF-α and p-NF-κB was evident. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of this fraction showed multiple constituents of interest, including esters, alkanes and amines.
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http://dx.doi.org/10.3390/molecules26082347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073239PMC
April 2021

Contribution of Attenuation of TNF-α and NF-κB in the Anti-Epileptic, Anti-Apoptotic and Neuroprotective Potential of Fruit and Its Chitosan Encapsulation.

Molecules 2021 Apr 17;26(8). Epub 2021 Apr 17.

Departament of Pharmacognosy, Riphah Institute of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan.

L. (Rosaceae) is one of the least reported and most understudied members of this family. It is native to the Himalayan regions of Pakistan and Nepal. The anti-convulsant effect of -hexane extract of fruit of was investigated in a pentylenetetrazole (PTZ)-induced animal model of epilepsy. Male Sprague-Dawley rats were divided into six groups (n = 7) including control, PTZ (40 mg/kg), diazepam (4 mg/kg) and -hexane extract (at 50, 150 and 300 mg/kg). Convulsive behavior was observed and resultant seizures were scored, animals sacrificed and their brains preserved. Chitosan nanoparticles were prepared using the ionic gelation method and characterized by UV-analysis, zeta potential and Fourier transform infrared spectroscopy (FTIR). The effects of all the treatments on the expression of phosphorylated cytokine tumor necrosis factor α (p-TNF-α) and phosphorylated transcription factor nuclear factor kappa B (p-NF-κB) expression in the cortex and hippocampus of the brains of treated rats were studied through enzyme linked immunosorbent assay (ELISA) and morphological differences and surviving neuronal number were recorded through hematoxylene and eosin (H&E) staining. Significant changes in seizures score and survival rate of rats were observed. Downregulation of neuro-inflammation, p-TNF-α and p-NF-κB was evident. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of this fraction showed multiple constituents of interest, including esters, alkanes and amines.
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http://dx.doi.org/10.3390/molecules26082347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073239PMC
April 2021

Modifications in lumbar facet joint are associated with spondylolisthesis in the degenerative spine diseases: a comparative analysis.

Acta Neurochir (Wien) 2021 03 6;163(3):863-871. Epub 2021 Jan 6.

Department of Surgery, Section of Neurosurgery, Aga Khan University Hospital, Stadium Road, Karachi, Sindh, 74800, Pakistan.

Background: Magnetic resonance imaging (MRI) is important in the assessment of degenerative spine disease. However, its role is limited in the identification of spinal instability; therefore, weight-bearing and dynamic studies like X-rays are required. The supine position eliminates the gravitational pull, corrects the vertebral slippage, and opens the facet joints leading to the collection of the synovial fluid into the joint space, which is detected on the MRI and can serve as a marker for instability. We aim to compare the facet fluid, facet hypertrophy, facet angle, and disc degenerative changes among the patients presenting with degenerative spondylolisthesis (DS) and those without.

Methods: We performed a retrospective review for all the patients treated at our institution from January 2015 to December 2016. Facet Fluid Index (FFI) (ratio of facet fluid width and facet joint width) was calculated to assess the joint fluid. The percentage of spondylolisthesis was measured on X-rays. Each radiological parameter was compared between the two groups, i.e., patients with DS and patients without DS. A p value < 0.05 was considered significant.

Results: In total, 61 patients, 28 with DS and 33 without DS, were enrolled. Baseline characteristics were similar in the two groups (p > 0.05). The average values of FFI, facet fluid width, and the difference between the superior and inferior facet were significantly higher in the group with instability (p < 0.05). Multivariate analysis demonstrated a 4.44 (95% confidence interval [CI] 2.03-5.365) times increase in the odds of instability with a unit increase in FFI, p < 0.0001.

Conclusions: We report a positive linear correlation between the facet joint effusion and facet hypertrophy on MRI and the percentage of vertebral translation on X-ray. Prospective studies will determine if these markers can play a role in predicting spinal instability.
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http://dx.doi.org/10.1007/s00701-020-04657-3DOI Listing
March 2021

The Glossopharyngo-Cochlear Triangle-Part I: Quantitative Anatomic Analysis of High-Riding Posterior Inferior Cerebellar Artery Aneurysms Exposed Through the Extended Retrosigmoid Approach.

Oper Neurosurg (Hagerstown) 2021 02;20(3):242-251

Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.

Background: An extended retrosigmoid approach can offer sufficient space for clip reconstruction of some high-riding posterior inferior cerebellar artery (PICA) aneurysms.

Objective: To quantitatively investigate the glossopharyngo-cochlear triangle (GCT) and anatomic structures within it.

Methods: Extended retrosigmoid craniotomies were performed on 10 sides of cadaveric heads, and the GCT was identified in each specimen. The length of the base and the area of the GCT were measured. The depth of the vertebrobasilar system and the abducens nerve to the GCT were measured. The proximal and distal exposable and controllable points on the vertebrobasilar system were identified. Two imaging-based patient selection algorithms are provided using the lengths from those points to the vertebral artery dural entry point and the superoinferior distances from those points to the inferior edge of the foramen magnum. Other factors related to accessibility via the GCT were investigated.

Results: The mean (standard deviation [SD]) area of the GCT was 45.7 (12.55) mm2. The mean (SD) depth of the abducens nerve was 14.3 (1.42) mm. The mean (SD) superoinferior distances from the foramen magnum to those points were 23.1 (7.39), 24.7 (8.25), 30.0 (9.56), and 32.6 (7.79) mm, respectively. The lower segment of the vertebrobasilar system was more superficial in the setting of a high-lying vertebrobasilar junction (VBJ) than a low-lying VBJ.

Conclusion: We describe the GCT in an extended retrosigmoid approach for high-riding PICA aneurysms and evaluate the spatial relationship of the neurovascular structures within it. Two potential algorithms are offered for preoperative patient selection.
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http://dx.doi.org/10.1093/ons/opaa356DOI Listing
February 2021

Benzimidazole Derivative Ameliorates Opioid-Mediated Tolerance during Anticancer- Induced Neuropathic Pain in Mice.

Anticancer Agents Med Chem 2021 ;21(3):365-371

Department of Basic Medical Sciences, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.

Background: Cancer is known to be the second significant cause of death worldwide. Chemotherapeutic agents such as platinum-based compounds are frequently used single-handedly or accompanied by additional chemotherapies to treat cancer patients. Chemotherapy-induced peripheral painful neuropathy is seen in around 40% of patients who are treated with platinum-based compounds, including cisplatin. This not only decreases the quality of life of patients but also patients' compliance with cisplatin.

Objectives: Nalbuphine, an opioid, is frequently used to treat acute and chronic pain, coupled with cisplatin in cancer patients. However, long term use of nalbuphine induces tolerance to its analgesic effects. We employed the same strategy to induce tolerance in mice.

Methods: Here, we investigated analgesic effects of 2-[(pyrrolidin-1-yl) methyl]-1H-benzimidazole (BNZ), a benzimidazole derivative, on nalbuphine-induced tolerance during cisplatin-induced neuropathic pain using hot plate test, tail-flick tests and von Frey filament in mouse models. Furthermore, we investigated the effects of BNZ on the expression of Tumor Necrosis Factor-alpha (TNF-α) in the spinal cord.

Results: The results showed that BNZ reduced tolerance to analgesic effects of nalbuphine and TNF-α expression in mice.

Conclusion: BNZ could be a potential drug candidate for the management of nalbuphine-induced tolerance in cisplatin-induced neuropathic pain.
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http://dx.doi.org/10.2174/1871520620999200818155031DOI Listing
January 2021

Tailoring the surgical corridor to the basilar apex in the pretemporal transcavernous approach: morphometric analyses of different neurovascular mobilization maneuvers.

Acta Neurochir (Wien) 2020 11 5;162(11):2731-2741. Epub 2020 Aug 5.

The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 350 W. Thomas Rd, Phoenix, AZ, 85013, USA.

Background: The pretemporal transcavernous approach (PTA) provides optimal exposure and access to the basilar artery (BA); however, the PTA can be invasive when vital neurovascular structures are mobilized. The goal of this study was to evaluate mobilization strategies to tailor approaches to the BA.

Methods: After an orbitozygomatic craniotomy, 10 sides of 5 cadaveric heads were used to assess the surgical access to the BA via the opticocarotid triangle (OCT), carotid-oculomotor triangle (COT), and oculomotor-tentorial triangle (OTT). Measurements were obtained, and morphometric analyses were performed for natural neurovascular positions and after each stepwise expansion maneuver. An imaginary line connecting the midpoints of the limbus sphenoidale and dorsum sellae was used as a reference to normalize the measurements of BA exposure and to facilitate the clinical applicability of this technique.

Results: In the OCT, the exposed BA segment ranged from - 1 ± 3.9 to + 6 ± 2.0 mm in length in its natural position. In the COT, the accessible BA segment ranged from - 4 ± 2.3 to - 2 ± 3.0 mm in length in its natural position. Via the OTT, the accessible BA segment ranged from - 7 ± 2.6 to - 5 ± 2.8 mm in length in its natural position. In the OCT, COT, and OTT, a posterior clinoidectomy extended the exposure down to - 6 ± 2.7, - 8 ± 2.5, and - 9 ± 2.9 mm, respectively.

Conclusions: This study quantitatively evaluated the need for the expansion maneuvers in the PTA to reach BA aneurysms according to the patient's anatomical characteristics.
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http://dx.doi.org/10.1007/s00701-020-04490-8DOI Listing
November 2020

Contralateral interoptic approach to paraclinoid aneurysms: a patient-selection algorithm based on anatomical investigation and clinical validation.

J Neurosurg 2020 Jun 12:1-9. Epub 2020 Jun 12.

Objective: Aneurysms that arise on the medial surface of the paraclinoid segment of the internal carotid artery (ICA) are surgically challenging. The contralateral interoptic trajectory, which uses the space between the optic nerves, can partially expose the medial surface of the paraclinoid ICA. In this study, the authors quantitatively measure the area of the medial ICA accessible through the interoptic triangle and propose a potential patient-selection algorithm that is based on preoperative measurements on angiographic imaging.

Methods: The contralateral interoptic trajectory was studied on 10 sides of 5 cadaveric heads, through which the medial paraclinoid ICA was identified. The falciform ligament medial to the contralateral optic canal was incised, the contralateral optic nerve was gently elevated, and the medial surface of the paraclinoid ICA was inspected via different viewing angles to obtain maximal exposure. The accessible area on the carotid artery was outlined. The distance from the distal dural ring (DDR) to the proximal and distal borders of this accessible area was measured. The superior and inferior borders were measured using the clockface method relative to a vertical line on the coronal plane. To validate these parameters, preoperative measurements and intraoperative findings were reviewed in 8 clinical cases.

Results: In the sagittal plane, the mean (SD) distances from the DDR to the proximal and distal ends of the accessible area on the paraclinoid ICA were 2.5 (1.52) mm and 8.4 (2.32) mm, respectively. In the coronal plane, the mean (SD) angles of the superior and inferior ends of the accessible area relative to a vertical line were 21.7° (14.84°) and 130.9° (12.75°), respectively. Six (75%) of 8 clinical cases were consistent with the proposed patient-selection algorithm.

Conclusions: The contralateral interoptic approach is a feasible route to access aneurysms that arise from the medial paraclinoid ICA. An aneurysm can be safely clipped via the contralateral interoptic trajectory if 1) both proximal and distal borders of the aneurysm neck are 2.5-8.4 mm distal to the DDR, and 2) at least one border of the aneurysm neck on the coronal clockface is 21.7°-130.9° medial to the vertical line.
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http://dx.doi.org/10.3171/2020.3.JNS193205DOI Listing
June 2020

Succinamide Derivatives Ameliorate Neuroinflammation and Oxidative Stress in Scopolamine-Induced Neurodegeneration.

Biomolecules 2020 03 13;10(3). Epub 2020 Mar 13.

State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen 518000, China.

Oxidative stress-mediated neuroinflammatory events are the hallmark of neurodegenerative diseases. The current study aimed to synthesize a series of novel succinamide derivatives and to further investigate the neuroprotective potential of these compounds against scopolamine-induced neuronal injury by in silico, morphological, and biochemical approaches. The characterization of all the succinamide derivatives was carried out spectroscopically via proton NMR (H-NMR), FTIR and elemental analysis. Further in vivo experiments showed that scopolamine induced neuronal injury, characterized by downregulated glutathione (GSH), glutathione S-transferase (GST), catalase, and upregulated lipid peroxidation (LPO). Moreover, scopolamine increased the expression of inflammatory mediators such as cyclooxygenase2 (COX2), nuclear factor kappa B (NF-kB), tumor necrosis factor (TNF-α), further associated with cognitive impairment. On the other hand, treatment with succinamide derivatives ameliorated the biochemical and immunohistochemical alterations induced by scopolamine, further supported by the results obtained from molecular docking and binding affinities.
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http://dx.doi.org/10.3390/biom10030443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175202PMC
March 2020

In Vivo, Proteomic, and In Silico Investigation of Sapodilla for Therapeutic Potential in Gastrointestinal Disorders.

Biomed Res Int 2019 10;2019:4921086. Epub 2019 Dec 10.

Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.

This study aims to delineate the effects of Linn. (Sapodilla) fruit chloroform (Mz.CHCl) and aqueous (Mz.Aq) extracts tested through different techniques. Antidiarrheal activity and intestinal fluid accumulation were examined by using castor oil-induced diarrhea and castor oil fluid accumulation models. Isolated rabbit jejunum tissues were employed for in vitro experiments. Antimotility and antiulcer were performed through charcoal meal transient time and ethanol-induced ulcer assay, molecular studies were conducted through proteomic analysis, and virtual screening was performed by using a discovery studio visualizer (DSV). Mz.CHCl and Mz.Aq extracts attributed dose-dependent (50-300 mg/kg) protection (20-100%) against castor oil-induced diarrhea and dose-dependently (50-300 mg/kg) inhibited intestinal fluid secretions in mice. Mz.CHCl and Mz.Aq extracts produce relaxation of spontaneous and K (80 Mm) induced contractions in isolated tissue preparations and decreased the distance moved by charcoal in the gastrointestinal transit model in rats. It showed gastroprotective effect in ulcerative stomach of rats and decreased levels of IL-18 quantified by proteomic analysis. Histopathological results showed ethanol-induced significant gastric injury, leading to cloudy swelling, hydropic degeneration, apoptosis, and focal necrosis in all gastric zones using hematoxylin and eosin (H&E) staining. Moreover, ethanol increased the activation and the expression of tumor necrotic factor (TNF-), cyclooxygenase (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (p-NFB). In silico results were comparative to in vitro results evaluated through virtual screening. Moreover, ethanol increased the activation and expression of tumor necrotic factor, cyclooxygenase, and nuclear factor kappa-light-chain-enhancer of activated B cells. This study exhibits the gastroprotective effect of extracts in the peritoneal cavity using a proteomic and in silico approach which reveals different energy values against target proteins, which mediate the gastrointestinal functions.
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http://dx.doi.org/10.1155/2019/4921086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925776PMC
May 2020

Role of stereotactic radiosurgery in the treatment of acromegaly.

J Pak Med Assoc 2018 Dec;68(12):1843-1845

Department of Surgery, Section of Neurosurgery, Aga Khan University Hospital, Karachi. Pakistan.

Acromegaly is a rare, indolent disease due to overproduction of growth hormone. Surgery is identified as primary treatment, but has its limitation, thus frequently requiring alternate treatment options as adjunct to surgery. Stereotactic radiosurgery (SRS) has been used as adjuvant and alternate therapy in patients with inoperable or residual disease; or those not fit for surgery. It has shown reasonable results for treating macroadenoma and tumours invading cavernous sinuses with significant reduction in tumour size and durable endocrinological remission. Factors favouring better outcomes include time from last resection to SRS, older age, peri-procedural withdrawal of medication, higher margin and maximum dose.Hypopituitarism is the most common side effects and requires yearly screening. With the new advances in the field Fractionated-stereotactic radiosurgery and cyber-knife robotic radiosurgery have been introduced with promising preliminary results..
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December 2018

Reading Between the Joints-Using Spinal Magnetic Resonance Imaging for Evaluation of Instability.

World Neurosurg 2017 Nov 14;107:1033-1034. Epub 2017 Sep 14.

Department of Surgery, Section of Neurosurgery Aga Khan University Hospital, Karachi, Pakistan.

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http://dx.doi.org/10.1016/j.wneu.2017.09.043DOI Listing
November 2017

In vitro inhibition of protease-activated receptors 1, 2 and 4 demonstrates that these receptors are not involved in an Acanthamoeba castellanii keratitis isolate-mediated disruption of the human brain microvascular endothelial cells.

Exp Parasitol 2014 Nov 2;145 Suppl:S78-83. Epub 2014 Apr 2.

Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan. Electronic address:

Granulomatous amoebic encephalitis is a rare but serious human disease leading almost always to death. The pathophysiology of amoebic encephalitis is better understood, while events leading to the constitution of brain infection are largely unknown. Traversal of the blood-brain barrier is a key step in amoebae invasion of the central nervous system and facilitated by amoebic extracellular proteases. By using specific inhibitors of protease-activated receptors 1, 2 and 4, here we studied the role of these host receptors in Acanthamoeba castellanii-mediated damage to human brain microvasculature endothelial cells (HBMEC), which constitute the blood-brain barrier. The primary HBMEC were incubated with A. castellanii-conditioned medium in the presence or absence of FR-171113 (selective inhibitor of protease-activated receptor 1), FSLLRY-NH2 (inhibitor of protease-activated receptor 2), and tcY-NH2 (inhibitor of protease-activated receptor 4). The HBMEC monolayer disruptions were assessed by microscopy using Eosin staining, while host cell cytotoxicity was determined by measuring the release of cytoplasmic lactate dehydrogenase. Zymographic assays were performed to determine the effects of inhibitors of protease-activated receptors on the extracellular proteolytic activities of A. castellanii. A. castellanii-conditioned medium produced severe HBMEC monolayer disruptions within 60 min. The selective inhibitors of protease-activated receptors tested did not affect HBMEC monolayer disruptions. On the contrary, pre-treatment of A. castellanii-conditioned medium with phenylmethylsulfonyl fluoride, a serine protease inhibitor, or heating for 10 min at 95°C abolished HBMEC monolayer disruptions. Additionally, inhibitors of protease-activated receptors tested, failed to block A. castellanii-mediated HBMEC cytotoxicity and did not affect extracellular proteolytic activities of A. castellanii. Protease-activated receptors 1, 2 and 4 do not appear to play a role in A. castellanii-mediated dysfunction of HBMEC, which constitute the blood-brain barrier. The role of additional protease-activated receptors in amoebic invasion of the central nervous system is discussed further.
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http://dx.doi.org/10.1016/j.exppara.2014.03.023DOI Listing
November 2014