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1.
Int J Mol Sci ; 25(12)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38928492

ABSTRACT

Heat stroke, a hazardous hyperthermia-related illness, is characterized by CNS injury, particularly long-lasting brain damage. A root cause for hyperthermic neurological damage is heat-induced proteotoxic stress through protein aggregation, a known causative agent of neurological disorders. Stress magnitude and enduring persistence are highly correlated with hyperthermia-associated neurological damage. We used an untargeted proteomic approach using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify and characterize time-series proteome-wide changes in dose-responsive proteotoxic stress models in medulloblastoma [Daoy], neuroblastoma [SH-SY5Y], and differentiated SH-SY5Y neuron-like cells [SH(D)]. An integrated analysis of condition-time datasets identified global proteome-wide differentially expressed proteins (DEPs) as part of the heat-induced proteotoxic stress response. The condition-specific analysis detected higher DEPs and upregulated proteins in extreme heat stress with a relatively conservative and tight regulation in differentiated SH-SY5Y neuron-like cells. Functional network analysis using ingenuity pathway analysis (IPA) identified common intercellular pathways associated with the biological processes of protein, RNA, and amino acid metabolism and cellular response to stress and membrane trafficking. The condition-wise temporal pathway analysis in the differentiated neuron-like cells detects a significant pathway, functional, and disease association of DEPs with processes like protein folding and protein synthesis, Nervous System Development and Function, and Neurological Disease. An elaborate dose-dependent stress-specific and neuroprotective cellular signaling cascade is also significantly activated. Thus, our study provides a comprehensive map of the heat-induced proteotoxic stress response associating proteome-wide changes with altered biological processes. This helps to expand our understanding of the molecular basis of the heat-induced proteotoxic stress response with potential translational connotations.


Subject(s)
Neurons , Proteome , Proteomics , Humans , Neurons/metabolism , Proteomics/methods , Proteome/metabolism , Cell Line, Tumor , Heat-Shock Response , Tandem Mass Spectrometry , Chromatography, Liquid , Cell Differentiation , Proteotoxic Stress
2.
J Physiol ; 601(12): 2407-2423, 2023 06.
Article in English | MEDLINE | ID: mdl-36951421

ABSTRACT

An evolutionary heat shock response (HSR) protects most living species, including humans, from heat-induced macromolecular damage. However, its role in the pathogenesis of heat stroke is unknown. We examined the whole genome transcriptome in peripheral blood mononuclear cells of a cohort of subjects exposed to the same high environmental heat conditions, who developed heat stroke (n = 19) versus those who did not (n = 19). Patients with heat stroke had a mean rectal temperature at admission of 41.7 ± 0.8°C, and eight were in deep coma (Glasgow Coma Score = 3). The transcriptome showed that genes involved in more than half of the entire chaperome were differentially expressed relative to heat stress control. These include the heat shock protein, cochaperone, and chaperonin genes, indicating a robust HSR. Differentially expressed genes also encoded proteins related to unfolded protein response, DNA repair, energy metabolism, oxidative stress, and immunity. The analysis predicted perturbations of the proteome network and energy production. Cooling therapy attenuated these alterations without complete restoration of homeostasis. We validated the significantly expressed genes by a real-time polymerase chain reaction. The findings reveal the molecular signature of heat stroke. They also suggested that a powerful HSR may not be sufficient to protect against heat injury. The overwhelming proteotoxicity and energy failure could play a pathogenic role. KEY POINTS: Most living species, including humans, have inherent heat stress response (HSR) that shields them against heat-induced macromolecular damage. The role of the HSR in subjects exposed to environmental heat who progressed to heat stroke versus those that did not is unknown. Our findings suggest that heat stroke induces a broad and robust HSR of nearly half of the total heat shock proteins, cochaperones, and chaperonin genes. Heat stroke patients exhibited inhibition of genes involved in energy production, including oxidative phosphorylation and ATP production. Significant enrichment of neurodegenerative pathways, including amyloid processing signalling, the Huntington's and Parkinson's disease signalling suggestive of brain proteotoxicity was noted. The data suggests that more than a powerful HSR may be required to protect against heat stroke. Overwhelming proteotoxicity and energy failure might contribute to its pathogenesis.


Subject(s)
Heat Stroke , Transcriptome , Humans , Coma , Leukocytes, Mononuclear , Heat-Shock Response/genetics , Heat-Shock Proteins/genetics , Heat Stroke/genetics
3.
Hum Genomics ; 16(1): 26, 2022 07 25.
Article in English | MEDLINE | ID: mdl-35879805

ABSTRACT

Genomics is advancing towards data-driven science. Through the advent of high-throughput data generating technologies in human genomics, we are overwhelmed with the heap of genomic data. To extract knowledge and pattern out of this genomic data, artificial intelligence especially deep learning methods has been instrumental. In the current review, we address development and application of deep learning methods/models in different subarea of human genomics. We assessed over- and under-charted area of genomics by deep learning techniques. Deep learning algorithms underlying the genomic tools have been discussed briefly in later part of this review. Finally, we discussed briefly about the late application of deep learning tools in genomic. Conclusively, this review is timely for biotechnology or genomic scientists in order to guide them why, when and how to use deep learning methods to analyse human genomic data.


Subject(s)
Deep Learning , Artificial Intelligence , Genome, Human/genetics , Genomics/methods , High-Throughput Nucleotide Sequencing , Humans
4.
Int J Mol Sci ; 24(14)2023 Jul 11.
Article in English | MEDLINE | ID: mdl-37511060

ABSTRACT

Adipocytes play a critical role in maintaining a healthy systemic metabolism by storing and releasing energy in the form of fat and helping to regulate glucose and lipid levels in the body. Adipogenesis is the process through which pre-adipocytes are differentiated into mature adipocytes. It is a complex process involving various transcription factors and signaling pathways. The dysregulation of adipogenesis has been implicated in the development of obesity and metabolic disorders. Therefore, understanding the mechanisms that regulate adipogenesis and the factors that contribute to its dysregulation may provide insights into the prevention and treatment of these conditions. RNA-binding motif single-stranded interacting protein 1 (RBMS1) is a protein that binds to RNA and plays a critical role in various cellular processes such as alternative splicing, mRNA stability, and translation. RBMS1 polymorphism has been shown to be associated with obesity and type 2 diabetes, but the role of RBMS1 in adipose metabolism and adipogenesis is not known. We show that RBMS1 is highly expressed during the early phase of the differentiation of the murine adipocyte cell line 3T3-L1 and is significantly upregulated in the adipose tissue depots and adipocytes of high-fat-fed mice, implying a possible role in adipogenesis and adipose metabolism. Knockdown of RBMS1 in pre-adipocytes impacted the differentiation process and reduced the expression of some of the key adipogenic markers. Transcriptomic and proteomic analysis indicated that RBMS1 depletion affected the expression of several genes involved in major metabolic processes, including carbohydrate and lipid metabolism. Our findings imply that RBMS1 plays an important role in adipocyte metabolism and may offer novel therapeutic opportunity for metabolic disorders such as obesity and type 2 diabetes.


Subject(s)
Adipocytes , Adipogenesis , Animals , Mice , 3T3-L1 Cells , Adipocytes/metabolism , Adipogenesis/genetics , Cell Differentiation/genetics , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Lipid Metabolism/genetics , Obesity/metabolism , Proteomics , Transcriptome
5.
Genomics ; 113(4): 1733-1741, 2021 07.
Article in English | MEDLINE | ID: mdl-33838280

ABSTRACT

Interferon-induced membrane proteins (IFITM) 3 gene variants are known risk factor for severe viral diseases. We examined whether IFITM3 variant may underlie the heterogeneous clinical outcomes of SARS-CoV-2 infection-induced COVID-19 in large Arab population. We genotyped 880 Saudi patients; 93.8% were PCR-confirmed SARS-CoV-2 infection, encompassing most COVID-19 phenotypes. Mortality at 90 days was 9.1%. IFITM3-SNP, rs12252-G allele was associated with hospital admission (OR = 1.65 [95% CI; 1.01-2.70], P = 0.04]) and mortality (OR = 2.2 [95% CI; 1.16-4.20], P = 0.01). Patients less than 60 years old had a lower survival probability if they harbor this allele (log-rank test P = 0.002). Plasma levels of IFNγ were significantly lower in a subset of patients with AG/GG genotypes than patients with AA genotype (P = 0.00016). Early identification of these individuals at higher risk of death may inform precision public health response.


Subject(s)
COVID-19/genetics , Genetic Predisposition to Disease , Membrane Proteins/genetics , RNA-Binding Proteins/genetics , SARS-CoV-2/genetics , Adult , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/virology , Female , Genetic Association Studies , Genotype , Humans , Interferons/genetics , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , SARS-CoV-2/pathogenicity
6.
Tech Coloproctol ; 26(7): 545-550, 2022 07.
Article in English | MEDLINE | ID: mdl-35499748

ABSTRACT

BACKGROUND: Endoscopic mucosal resection (EMR) is the primary treatment modality for superficial gastrointestinal mucosal lesions > 2 cm. However, the procedure carries some risk of complications including bleeding, perforation, and local recurrence. This study aimed to examine factors associated with EMR outcomes, especially in terms of local recurrence. METHODS: This study retrospectively evaluated patients who underwent EMR and full closure with prophylactic clips for upper and lower gastrointestinal lesions > 2 cm at Cleveland Clinic Florida, between January 2013 and December 2018 with follow-up endoscopic evaluation for recurrence. RESULTS: A total of 2031 endoscopic polypectomy cases were examined; 307 EMR procedures among 271 patients (52% were female, mean age 65.6 ± 11.1 years) who satisfied the inclusion criteria were included in the study. There were no perforations reported. The rate of post-polypectomy delayed bleeding was 1.6%, and the local recurrence rate in this cohort was 7.1%. Recurrent cases were successfully endoscopically managed. In the multivariate regression analysis, age > 70 years (OR = 3.20, 95% CI 1.17-8.76, p = .023), body mass index (OR = 1.12, 95% CI 1.03-1.23 p = .008), and lesion size ≥ 35 mm (OR = 11.51, 95% CI 3.54-37.40, p = < .001) were independent predictors for recurrence. CONCLUSIONS: Age > 70 years, increased lesion size, and obesity were found to be independent predictors of local recurrence among EMR procedures for gastrointestinal lesions > 2 cm. However, there is a need for larger-scale studies on this topic.


Subject(s)
Endoscopic Mucosal Resection , Aged , Endoscopic Mucosal Resection/adverse effects , Endoscopic Mucosal Resection/methods , Endoscopy , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/surgery , Retrospective Studies , Risk Factors , Treatment Outcome
7.
Comput Electr Eng ; 103: 108391, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36119394

ABSTRACT

All witnessed the terrible effects of the COVID-19 pandemic on the health and work lives of the population across the world. It is hard to diagnose all infected people in real time since the conventional medical diagnosis of COVID-19 patients takes a couple of days for accurate diagnosis results. In this paper, a novel learning framework is proposed for the early diagnosis of COVID-19 patients using hybrid deep fusion learning models. The proposed framework performs early classification of patients based on collected samples of chest X-ray images and Coswara cough (sound) samples of possibly infected people. The captured cough samples are pre-processed using speech signal processing techniques and Mel frequency cepstral coefficient features are extracted using deep convolutional neural networks. Finally, the proposed system fuses extracted features to provide 98.70% and 82.7% based on Chest-X ray images and cough (audio) samples for early diagnosis using the weighted sum-rule fusion method.

8.
J Clin Gastroenterol ; 55(4): 355-360, 2021 04 01.
Article in English | MEDLINE | ID: mdl-32796193

ABSTRACT

BACKGROUND AND AIM: There is limited data regarding the safety of endoscopic mucosal resection (EMR) in the cirrhotic population. Our study aimed to evaluate the safety of colonoscopic EMR in cirrhosis. MATERIALS AND METHODS: This was a retrospective review of cirrhotics who underwent colonic EMR at 8 Cleveland Clinic Centers between January 1, 2006, and December 31, 2018. Patient data including polyp details and complications occurring within 30 days of the procedure were noted. Univariable and multivariable logistic regression analyses were conducted to find risk factors for post-EMR bleeding. RESULTS: A total of 238 patients who underwent EMR were included. There were 145 males (60.9%) and the mean age was 61.9±8.6 years. Immediate and delayed bleeding, and postpolypectomy syndrome rates were 9.2%, 5.8%, and 1.3%, respectively. Significant risk factors for postpolypectomy bleeding were: increased age (P=0.001), procedure duration >37 minutes (P=0.001), antiplatelet use within 5 days (P=0.023), and lesion diameter >15 mm (P=0.004). Multivariable analysis revealed independent predictors of procedure-related bleeding: age above 65 years [odds ratio (OR) 2.14, P=0.044], antiplatelet use within 5 days (OR 2.42, P=0.047), right colon polyp (OR 3.51, P=0.001), and lesion diameter >15 mm (OR 3.22, P=0.003). CONCLUSIONS: EMR in cirrhotics has an acceptable bleeding risk. Age above 65 years, right colon polyp, polyp size >15 mm, and use of antiplatelets within 5 days are independent risk factors for bleeding.


Subject(s)
Colonic Polyps , Postoperative Hemorrhage , Aged , Colonic Polyps/surgery , Colonoscopy , Humans , Liver Cirrhosis/complications , Male , Middle Aged , Postoperative Hemorrhage/epidemiology , Postoperative Hemorrhage/etiology , Retrospective Studies , Risk Factors
9.
BMC Surg ; 21(1): 120, 2021 Mar 08.
Article in English | MEDLINE | ID: mdl-33685447

ABSTRACT

BACKGROUND: Most of the head and neck cancers are time-critical and need urgent surgical treatment. Our unit is one of the departments in the region, at the forefront in treating head and neck cancers in Pakistan. We have continued treating these patients in the COVID-19 pandemic with certain modified protocols. The objective of this study is to share our experience and approach towards head and neck reconstruction during the COVID-19 pandemic. RESULTS: There were a total of 31 patients, 20 (64.5%) were males and 11 (35.4%) patients were females. The mean age of patients was 52 years. Patients presented with different pathologies, i.e. Squamous cell carcinoma n = 26 (83.8%), mucoepidermoid carcinoma n = 2 (6.4%), adenoid cystic carcinoma n = 2 (6.4%) and mucormycosis n = 1 (3%). The reconstruction was done with loco-regional flaps like temporalis muscle flap n = 12 (38.7%), Pectoralis major myocutaneous flap n = 8 (25.8%), supraclavicular artery flap n = 10 (32.2%) and combination of fore-head, temporalis major and cheek rotation flaps n = 1 (3%). Defects involved different regions like maxilla n = 11 (35.4%), buccal mucosa n = 6 (19.3%), tongue with floor of mouth n = 6 (19.3%), mandible n = 4 (12.9%), parotid gland, mastoid n = 3 (9.6%) and combination of defects n = 1 (3%). Metal reconstruction plate was used in 3 (9.6%) patients with mandibular defects. All flaps survived, with the maximum follow-up of 8 months and minimum follow-up of 6 months. CONCLUSION: Pedicled flaps are proving as the workhorse for head and neck reconstruction in unique global health crisis. Vigilant use of proper PPE and adherence to the ethical principles proves to be the only shield that will benefit patients, HCW and health system.


Subject(s)
COVID-19 , Head and Neck Neoplasms , Plastic Surgery Procedures , Female , Head and Neck Neoplasms/surgery , Humans , Male , Middle Aged , Plastic Surgery Procedures/methods , Surgical Flaps
10.
Sensors (Basel) ; 21(8)2021 Apr 14.
Article in English | MEDLINE | ID: mdl-33920008

ABSTRACT

Long-range radio (LoRa) communication is a widespread communication protocol that offers long range transmission and low data rates with minimum power consumption. In the context of solid waste management, only a low amount of data needs to be sent to the remote server. With this advantage, we proposed architecture for designing and developing a customized sensor node and gateway based on LoRa technology for realizing the filling level of the bins with minimal energy consumption. We evaluated the energy consumption of the proposed architecture by simulating it on the Framework for LoRa (FLoRa) simulation by varying distinct fundamental parameters of LoRa communication. This paper also provides the distinct evaluation metrics of the the long-range data rate, time on-air (ToA), LoRa sensitivity, link budget, and battery life of sensor node. Finally, the paper concludes with a real-time experimental setup, where we can receive the sensor data on the cloud server with a customized sensor node and gateway.

11.
Environ Monit Assess ; 193(7): 382, 2021 Jun 05.
Article in English | MEDLINE | ID: mdl-34089115

ABSTRACT

Oxycarenus hyalinipennis Costa is a polyphagous insect pest and can develop insecticide resistance. The resistance of O. hyalinipennis to neonicotinoids (clothianidin and dinotefuran), flonicamid, and conventional insecticides; carbamates (methomyl and carbosulfon), organophosphates (chlorpyrifos and malathion), and pyrethroids (cypermethrin and zeta-cypermethrin) was evaluated. The O. hyalinipennis populations were sampled from four locations in Pakistan and performed bioassays against the insecticides by leaf dip protocol. The O. hyalinipennis' populations showed low resistance to carbosulfan (resistance ratio (RR) = 2.06-6.34) and methomyl (RR = 2.78-7.27), moderate to high resistance to chlorpyrifos (RR = 30-45), malathion (RR = 20.29-88.19), and flonicamid (RR = 14.24-46.97), in comparison with the susceptible strain. Susceptibility to low resistance against cypermethrin (RR = 1.27-2.82), zeta-cypermethrin (RR = 2.62-3.38), and clothianidin (RR = 1.74-3.40), and low to moderate resistance to dinotefuran (RR = 3.84-13.43) in the field populations, was observed compared to the susceptible strain. A rotational usage of carbamates and pyrethroids with an integrated pest management tool should be considered to deal with O. hyalinipennis' insecticide resistance.


Subject(s)
Insecticides , Environmental Monitoring , Insecticides/toxicity , Neonicotinoids , Niacinamide/analogs & derivatives , Pakistan
12.
J Neurochem ; 153(1): 120-137, 2020 04.
Article in English | MEDLINE | ID: mdl-31486527

ABSTRACT

Previous studies documented up-regulation of peptidase neurolysin (Nln) after brain ischemia, however, the significance of Nln function in the post-stroke brain remained unknown. The aim of this study was to assess the functional role of Nln in the brain after ischemic stroke. Administration of a specific Nln inhibitor Agaricoglyceride A (AgaA) to mice after stroke in a middle cerebral artery occlusion model, dose-dependently aggravated injury measured by increased infarct and edema volumes, blood-brain barrier disruption, increased levels of interleukin 6 and monocyte chemoattractant protein-1, neurological and motor deficit 24 h after stroke. In this setting, AgaA resulted in inhibition of Nln in the ischemic hemisphere leading to increased levels of Nln substrates bradykinin, neurotensin, and substance P. AgaA lacked effects on several physiological parameters and appeared non-toxic to mice. In a reverse approach, we developed an adeno-associated viral vector (AAV2/5-CAG-Nln) to overexpress Nln in the mouse brain. Applicability of AAV2/5-CAG-Nln to transduce catalytically active Nln was confirmed in primary neurons and in vivo. Over-expression of Nln in the mouse brain was also accompanied by decreased levels of its substrates. Two weeks after in vivo transduction of Nln using the AAV vector, mice were subjected to middle cerebral artery occlusion and the same outcome measures were evaluated 72 h later. These experiments revealed that abundance of Nln in the brain protects animals from stroke. This study is the first to document functional significance of Nln in pathophysiology of stroke and provide evidence that Nln is an endogenous mechanism functioning to preserve the brain from ischemic injury.


Subject(s)
Brain/physiopathology , Metalloendopeptidases/physiology , Stroke/physiopathology , Animals , Edema , Gene Expression Regulation , Glycerides/pharmacology , Infarction, Middle Cerebral Artery , Male , Metalloendopeptidases/antagonists & inhibitors , Metalloendopeptidases/genetics , Mice , Recombinant Proteins/drug effects , Stroke/etiology , Stroke/pathology , Transfection
13.
J Nat Prod ; 83(5): 1383-1393, 2020 05 22.
Article in English | MEDLINE | ID: mdl-32364734

ABSTRACT

The ethanolic root extract of Berberis brevissima afforded a new bisbenzylisoquinoline alkaloid, 13-nitrochondrofoline (2), and two known bisbenzylisoquinoline alkaloids, chondrofoline (1) and curine (4). The acetylation of chondrofoline (1) gave O-acetylchondrofoline (3). The dimeric structures of 1 and 2 were studied through variable-temperature 1H NMR spectroscopy at 25, 40, 60, and 80 °C and conformational analysis, using density functional theory employing the M06-2X functional and the 6-31G* basis set. The in vitro antitrypanosomal activity of compounds 1, 2, 3, and 4 against Trypanosoma brucei showed significant potential with MIC values of 2.6, 2.2, 2.3, and 3.8 µM, respectively. Molecular docking evaluation of alkaloids 1, 2, 3, and 4 against known T. brucei protein targets revealed T. brucei phosphodiesterase B1 to be the preferred target. The docking energies of the alkaloids with Tb6PGL (PDB 3EB9) ranged from -88.8 to -106.0 kJ/mol and was comparable to the cocrystallized ligand, citrate (Edock = -78.3 kJ/mol). It seems reasonable that the curine alkaloids may compete with the natural substrates for these protein targets and serve as leads in designing and developing more potent and selective drugs against T. brucei.


Subject(s)
Berberis/chemistry , Isoquinolines/chemistry , Isoquinolines/pharmacology , Trypanocidal Agents/pharmacology , Animals , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Molecular Docking Simulation , Molecular Structure , Phosphodiesterase Inhibitors/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Proton Magnetic Resonance Spectroscopy , Temperature , Trypanocidal Agents/chemistry , Trypanosoma brucei brucei/drug effects
14.
BMC Health Serv Res ; 19(1): 835, 2019 Nov 14.
Article in English | MEDLINE | ID: mdl-31727053

ABSTRACT

In the original publication of this article [1], an author's name needs to be revised from Babar Tasneen Shaikh to Babar Tasneem Shaikh.

15.
BMC Health Serv Res ; 19(1): 715, 2019 Oct 21.
Article in English | MEDLINE | ID: mdl-31638970

ABSTRACT

BACKGROUND: Delayed diagnosis of Oral Cancer (OC) can mean a difference in quality and expectancy of life for the patient. This delay could be from the healthcare side, or more importantly from the patient's side. Globally, there are studies enumerating the causes for delays from the patients' side in seeking healthcare for Oral Cancer; however, no similar research is found in the context of Pakistan. This study endeavoured to understand the health seeking behaviour, reasons for delay in consultation and the impact on OC patients' lives. METHODS: In-depth interviews were conducted with randomly selected OC patients at a private sector tertiary care facility in Islamabad (who met the inclusion criteria of having successfully been treated for Oral Cancer) which caters to the most diverse population for the treatment of Oral Cancer. Theoretical saturation was achieved at 14 interviews. All participants gave verbal consent for participation, which was recorded prior to the interviews. RESULTS: Patients (age range 43-68 years) had received the surgical treatment and radiation. The reported delay before seeking a proper medical advice ranged from 1 month to 2 years. Lack of awareness about OC risk factors, symptoms, and whom to approach for treatment were the main reasons. Most respondents relied on self-treatment considering the non-healing wound/ulcer to be a minor issue until they were advised a consultation with a specialist. Treatment started within 1-3 months after a confirmed diagnosis on biopsy. The reported average expenditure on treatment was US$5000-10,000, mostly covered through a private health insurance and others borrowed the money. CONCLUSION: A socio-behavioural change campaign for the general population can result in earlier presentation of the OC, minimizing the financial burden on the patient as well as the health system, and improving the quality of life of the patients.


Subject(s)
Health Behavior , Mouth Neoplasms/diagnosis , Patient Acceptance of Health Care/statistics & numerical data , Adult , Aged , Disease Progression , Female , Humans , Male , Middle Aged , Mouth Neoplasms/psychology , Pakistan , Patient Acceptance of Health Care/psychology , Qualitative Research , Retrospective Studies , Time-to-Treatment
16.
Phytother Res ; 33(10): 2661-2684, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31453659

ABSTRACT

Several reviews have been published on Artemisia's derived natural products, but it is the first attempt to review the chemistry and pharmacology of more than 80 alkaloids and allied nitrogen compounds obtained from various Artemisia species (covering the literature up to June 2018). The pharmacological potential and unique skeleton types of certain Artemisia's alkaloids provoke the importance of analyzing Artemisia species for bioactive alkaloids and allied nitrogen compounds. Among the various types of bioactive Artemisia's alkaloids, the main classes were the derivatives of rupestine (pyridine-sesquiterpene), lycoctonine (diterpene), pyrrolizidine, purines, polyamine, peptides, indole, piperidine, pyrrolidine, alkamides, and flavoalkaloids. The rupestine derivatives are Artemisia's characteristic alkaloids, whereas the rest are common alkaloids found in the family Asteraceae and chemotaxonomically links the genus Artemisia with the tribes Anthemideae. The most important biological activities of Artemisia's alkaloids are including hepatoprotective, local anesthetic, ß-galactosidase, and antiparasitic activities; treatment of angina pectoris, opening blocked arteries, as a sleep-inducing agents and inhibition of HIV viral protease, CYP450, melanin biosynthesis, human carbonic anhydrase, [3H]-AEA metabolism, kinases, and DNA polymerase ß1 . Some of the important nitrogen metabolites of Artemisia include pellitorine, zeatin, tryptophan, rupestine, and aconitine analogs, which need to be optimized and commercialized further.


Subject(s)
Alkaloids/pharmacology , Artemisia/chemistry , Alkaloids/analysis , Humans , Nitrogen Compounds/pharmacology , Plant Extracts/pharmacology
17.
J Pak Med Assoc ; 68(6): 950-952, 2018 Jun.
Article in English | MEDLINE | ID: mdl-30323367

ABSTRACT

Optic nerve Schwannoma is a very rare tumour described in literature. The rarity of this tumour is due to the fact that the optic nerve is myelinated by oligodendrocytes. We present a case of an ancient optic nerve schwannoma in a 16 year old girl who presented to the clinic with right sided proptosis and bilateral loss of vision. She underwent complete excision of the tumour via a craniotomy and histopathology was confirmatory. The various theories explaining the origin of this tumour are discussed along with surgical nuances of removing this tumour. The importance of taking every precaution to preserve vision and avoiding imaging confusion in patients with von Recklinghausen syndrome is also discussed. Only 6 cases of optic nerve schwannomas are described in literature while none have been described in a patient with NF 1.


Subject(s)
Neurilemmoma/diagnostic imaging , Neurofibromatosis 1/diagnosis , Optic Nerve Neoplasms/diagnostic imaging , Adolescent , Female , Humans , Magnetic Resonance Imaging , Neurilemmoma/complications , Neurilemmoma/pathology , Neurilemmoma/surgery , Neurofibromatosis 1/complications , Neurofibromatosis 1/pathology , Optic Nerve Neoplasms/complications , Optic Nerve Neoplasms/pathology , Optic Nerve Neoplasms/surgery
18.
J Pak Med Assoc ; 68(2): 170-174, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29479088

ABSTRACT

OBJECTIVE: To determine the presentation and frequency of various intracranial neoplasms and assess outcomes for patients who underwent surgery without neuronavigation. METHODS: This retrospective study was conducted at Combined Military Hospital, Peshawar, Pakistan, and comprised medical records related to the period from August 2011 to July 2014. Patient histories, examination reports and preoperative and post-operative radiological scans were reviewed and extent of excision was determined based on these coupled with recurrence rates. Intraoperatively, tumour excision was determined largely by the experience of the surgeon and preoperative planning using bony landmarks and radiological scans as an objective guide to resection. SPSS 21 was used for data analysis. RESULTS: Of the 143 patients, 83(57.9%) were males and 60(42.1%)were females. Gliomas were the most common tumours, occurring in 20(33.3%) females and 35(42.2%) males. One-year survival rate for grade 4 astrocytomas was poor (39.4%) and was excellent for meningiomas (100%) and pituitary tumours (100%). CONCLUSIONS: Time-tested methods of careful neurological examination and knowledge of neuroanatomy can allow a surgeon with limited resources to plan and accommodate for accurate tumour resection with adequate margins.


Subject(s)
Brain Neoplasms/surgery , Glioma/surgery , Meningeal Neoplasms/surgery , Meningioma/surgery , Neurosurgical Procedures/methods , Adenoma/surgery , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Neuronavigation , Pituitary Neoplasms/surgery , Retrospective Studies , Survival Rate , Young Adult
19.
Pak J Med Sci ; 34(3): 691-695, 2018.
Article in English | MEDLINE | ID: mdl-30034441

ABSTRACT

OBJECTIVE: This study was conducted to assess outcomes in patients with hydrocephalus who underwent ventriculoperitoneal shunting at Keen's point. METHODS: This retrospective study was conducted in Combined Military Hospital (CMH) Peshawar. Time frame was four years from January 2011 to January 2015. The presenting complaints, clinical findings, investigations, treatment plans and surgical outcomes were noted. Ventriculo-Peritoneal (VP) shunting was done at Keen's point. The presence of shunt complications in the first week post-surgery was noted and at a three-month follow up in the outpatient department. General condition of the patient, shunt complications, presence of seizure and worsening of vision were noted. RESULTS: Study included 143 patients, out of whom 46 were females and 95 were male patients. Most common causes of hydrocephalus were congenital (79). Majority of adults had hydrocephalus due to central nervous system tumors while congenital hydrocephalus in children was most frequently due to aqueductal stenosis. Good clinical improvement was seen in 114 patients after shunt placement, satisfactory in 20 patients, 7 patients died while we observed no change in two patients. CONCLUSION: Our experience with VP shunting at Keen's point resulted in excellent outcomes. It can be used for the management of hydrocephalus both in pediatric as well as adult population.

20.
Pak J Med Sci ; 34(6): 1412-1417, 2018.
Article in English | MEDLINE | ID: mdl-30559795

ABSTRACT

OBJECTIVES: To study clinical and radiological outcomes in patients who had undergone the procedure of anterior cervical discectomy and fusion with titanium or PEEK (polyetheretherketone) cages for cervical disc prolapse. METHODS: This is a retrospective/non-randomized study which was conducted at the Combined Military Hospital Peshawar. Study interval was four years from 1st October, 2010 to 31st September, 2014. Total number of included patients were 149. All of the patients had undergone the procedure of anterior cervical discectomy and fusion with titanium or PEEK (polyetheretherketone) cages. All of the patients had plain MRI cervical spine done for diagnosis of anterior cervical disc prolapse. RESULTS: Most of the patients had stenosis at the C5 / C6 (PEEK cage group 63% and titanium cage group 47.6%) and C6 / C7 (PEEK cage group 15.38% and titanium cage group 19.04%) cervical level. Bi-level involvement was also seen. In the patients who complained of brachialgia, total resolution of symptoms was seen after the operation. Three (2.01%) of the patients in titanium cage group, who presented with axial neck pain, continued to complain of pain after the operation. Four (2.6%) of the patients in PEEK (polyetheretherketone) cage group and 2 (1.3%) in titanium cage group complained of pain at the donor site (iliac crest). Fusion rate was 100% with both titanium and PEEK (polyetheretherketone) cages at one year. CONCLUSION: Results with titanium and PEEK (polyetheretherketone) cages are excellent. There was no significant difference in clinical and radiological outcome between two groups of patients (p > 0.05). Fusion rate was 100% at one year with both cages.

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