Publications by authors named "Alireza Zali"

68 Publications

Role of interferon therapy in severe COVID-19: the COVIFERON randomized controlled trial.

Sci Rep 2021 04 13;11(1):8059. Epub 2021 Apr 13.

Department of Surgery, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNβ compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNβ1a and IFNβ1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNβ1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNβ1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400 mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNβ1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI 1.10-5.17, P-value = 0.031) while the IFNβ1b indicated no significant difference compared with the control; HR; 1.42, (95% CI 0.63-3.16, P-value = 0.395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNβ1a group and 30% in the IFNβ1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNβ1a arm. This finding needs further confirmation in larger studies.Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768).
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http://dx.doi.org/10.1038/s41598-021-86859-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044200PMC
April 2021

Correction to: Stem Cell-Derived Exosomes as Treatment for Stroke: a Systematic Review.

Stem Cell Rev Rep 2021 Apr;17(2):439

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.1007/s12015-021-10153-7DOI Listing
April 2021

Seroprevalence of SARS-CoV-2 in Parkinson's Disease Patients: A Case-Control Study.

Mov Disord 2021 04 17;36(4):794-795. Epub 2021 Mar 17.

Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.1002/mds.28580DOI Listing
April 2021

Presence of SARS-CoV-2 in the air of public places and transportation.

Atmos Pollut Res 2021 Mar 2;12(3):302-306. Epub 2021 Jan 2.

Department of Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.

This study investigated the presence of SARS-CoV-2 in air of public places such as shopping centers, a post office, banks, governmental offices, and public transportation facilities including an airport, subways, and buses in Tehran, Iran. A total of 28 air samples were collected from the eight groups of public and transportation locations. The airborne particle samples were collected on PTFE or glass fiber filters using two types of samplers with flow rates of 40 and 3.5 L/min, respectively. The viral samples were leached and concentrated, and RNA was extracted from each. The presence of viral RNA was evaluated using novel coronavirus nucleic acid diagnostic real time PCR kits. In 64% of the samples, SARS-CoV-2 RNA (62% and 67% from the public places and transportation, respectively) was detected. Positive samples were detected in banks (33%), shopping centers (100%), governmental offices (50%), the airport (80%), subway stations (50%), subway trains (100%), and buses (50%). Logistic regression showed that number of people present during the sampling and the sampled air volume were positively associated with presence of SARS-CoV-2; while the percentage of people with masks, air temperature, and sampling site's volume were negatively related to SARS-CoV-2's presence. However, none of these associations were statistically significant. This study showed that most public places and transportation vehicles were contaminated with SARS-CoV-2. Thus, strategies to control the spread of COVID-19 should include reducing the number of people in indoor spaces, more intense disinfection of transport vehicles, and requiring people to wear masks.
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http://dx.doi.org/10.1016/j.apr.2020.12.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833664PMC
March 2021

Efficacy, safety, and tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain: a randomized, double-blind, placebo-controlled study.

Daru 2021 Jan 21. Epub 2021 Jan 21.

Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Breakthrough pain (BTP) is an important challenge in treatment and requires a rapid onset of action for pain control. BTP should be adequately controlled with a stable dose of a short-acting oral opioid. So far, no drug is available for the treatment of BTP in cancer patients in Iran, so we designed the first study in Iran to investigate the effect of sublingual fentanyl in relief of pain episodes in these patients.

Objective: The purpose of this study was to evaluate the efficacy and safety of sublingual fentanyl in the treatment of breakthrough pain in cancer patients.

Method: This study was a randomized double-blind placebo-controlled clinical trial in cancer patients with breakthrough pain (at least 1-4 episodes of acute pain with moderate to severe pain daily) referred to the pain clinic of Akhtar and Masih Daneshvari hospitals in 2019. The study consisted of two stages: 100 patients were selected by simple, non-random sampling and entered the open-label titration phase. The primary efficacy endpoint was the sum of pain intensity difference over 30 min post-administration. Secondary efficacy endpoints included pain intensity difference (PID) and pain relief (PR) throughout the 60-min post-dose assessment period. In the double-blind study, patients were randomly divided into two groups of placebo (n=50) and intervention (sublingual fentanyl tablet) (n=50). For evaluation of efficacy, 10 episodes were treated in each group and the results were recorded by the patient. (Clinical trial registration: IRCT20131124015515N8).

Results: A total of 100 patients entered the titration phase, primary efficacy of sublingual fentanyl was 3.5±0.6 and secondary efficacy of sublingual fentanyl (60 min, after treatment) was 0.3±0.6 which was statistically significant. In the titration phase, the treatment success rate was 100%. In the double-blind phase of the study, the pain intensity in multiple episodes showed a significant improvement at 15, 30, 45, and 60 min after drug administration (P=0.0001). The intensity of pain in each episode was significantly decreased compared to the next episode (P=0.0001). The mean frequency of pain episodes in the sublingual fentanyl group showed a significant decrease (P=0.0001). The most common adverse drug events in the titration phase were drowsiness (20%), dizziness (7%), and nausea 4%, and in the double-blind phase only drowsiness (12%). (Cancer Research Center, Shahid Beheshti University of Medical Sciences, Survey).

Conclusion: Sublingual fentanyl appears to be effective for patients with rapid-onset analgesia, has short-acting duration, is effective medication, safe, and well tolerated. It is a suitable choice in Iranian patients with chronic cancer-related pain controlled suffering from acute pain episodes related to cancer.
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http://dx.doi.org/10.1007/s40199-020-00381-6DOI Listing
January 2021

Clinical and Epidemiological Characteristics of Postdischarge Patients With COVID-19 in Tehran, Iran: Protocol for a Prospective Cohort Study (Tele-COVID-19 Study).

JMIR Res Protoc 2021 Feb 2;10(2):e23316. Epub 2021 Feb 2.

HIV/Sexually Transmitted Infection Surveillance Research Center, and World Health Organization Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran.

Background: COVID-19 was declared a pandemic on March 11, 2020. Given that the severe shortage of hospital beds has led to early discharge and insufficient patient education on home care routines and isolation protocols, the close follow-up of patients and their immediate relatives is an integral part of transitioning from hospital care to home care for patients with COVID-19.

Objective: We designed the Tele-COVID-19 prospective cohort to follow-up with COVID-19 patients in Tehran, Iran, and improve health care delivery and the recording of postdischarge patients' clinical profiles.

Methods: All adult patients who were admitted to the COVID-19 wards of teaching hospitals in Tehran, Iran were eligible to participate in this cohort study. At baseline, patients were recruited from 4 major hospitals from March 9, 2020 to May 20, 2020. Telephone follow-ups, which were led by volunteer medical students, were conducted on postdischarge days 1-3, 5, 7, 10, and 14. We collected data on a range of sociodemographic, epidemiological, and clinical characteristics by using a standard questionnaire.

Results: Of the 950 patients with confirmed COVID-19 who were approached, 823 (response rate: 86.6%) consented and were enrolled into the cohort. Of the 823 participants, 449 (54.5%) were male. The mean age of participants was 50.1 years (SD 12.6 years). During the initial data collection phase, more than 5000 phone calls were made and over 577 reports of critical patients who were in need of urgent medical attention were recorded.

Conclusions: The Tele-COVID-19 cohort will provide patients with sufficient education on home care and isolation, and medical advice on care and the proper use of drugs. In addition, by preventing unnecessary hospital returns and providing information on household SARS-CoV-2 transmission as early as possible, this cohort will help with effective disease management in resource-limited settings.

International Registered Report Identifier (irrid): DERR1-10.2196/23316.
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http://dx.doi.org/10.2196/23316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857388PMC
February 2021

The Long-term Effects of Percutaneous Laser Disc Decompression (PLDD) Treatment on Lumbar Disc Protrusion: A 2-Year Follow-up.

J Lasers Med Sci 2020 3;11(4):427-432. Epub 2020 Oct 3.

Research Center for Neurosurgery and Functional Nerves, Shahid Beheshti University of Medical Sciences, Shohad-a-Tajrish Hospital, Tehran, Iran.

Nowadays many physicians have focused their attention on using low invasive methods for the treatment of disc protrusion. Thus, the current study was carried out to evaluate the effect and therapeutic outcomes of clinical percutaneous laser disc decompression (PLDD) in the treatment of chronic low back pain caused by disc protrusion during a two-year follow-up. This historical cohort study was conducted on 40 patients, who were suffering from chronic low back pain caused by disc protrusion diagnosed, and referred to the pain clinic of Akhtar Hospital from March to August 2016 were treated with PLDD and were followed up for at least two years after performing PLDD (from 2018 to 2019). All the information has been extracted using medical records and patient interview. The severity of pain was measured by the Numeric Rating Scale (NRS), and the Oswestry disability index (ODI) was measured before and two years after the treatment. The most common sites for two-level PLDD were L4-S1 and L3-L5, and the most common sites for one-level PLDD were L5-S1 and L4-L5. Overall, the levels of pain and functional disability two years after PLDD showed significant improvements ( =0.0001). The results revealed no statistically significant differences in NRS and ODI scores between the two groups of men and women two years after PLDD ( >0.05). Furthermore, they indicated no statistically significant differences in NRS and ODI scores between the different disc protrusion levels two years after PLDD ( >0.05). It seems that the PLDD is a low-invasive, safe, and effective method that can be used in patients with chronic low back pain caused by a disc protrusion. Therefore, it can be considered as a suitable choice in treating patients with chronic low back pain caused by a disc protrusion.
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http://dx.doi.org/10.34172/jlms.2020.67DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736942PMC
October 2020

Combination therapy of IFNβ1 with lopinavir-ritonavir, increases oxygenation, survival and discharging of sever COVID-19 infected inpatients.

Int Immunopharmacol 2021 Mar 26;92:107329. Epub 2020 Dec 26.

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Interferon Beta-1a (IFN-β1-a), an immunomodulatory mediator with antiviral effects, has shown in vivo and in vitro activities especially on coronavirus including SARS-CoV-2. COVID-19 defined as the disease caused by infection with SARS-CoV-2. The virus has been illustrated inhibits the production of IFN-β1-a from inflammatory cells. We conducted a retrospective study of all adult confirmed COVID-19 hospitalized patients who received combination of three doses of 12 million international units of IFN-β1-a and Lopinavir 400 mg and Ritonavir 100 mg every 12 h (case group) for 14 days besides standard care and age- and sex- matched COVID-19 patients with receiving lopinavir/ritonavir (control group) at Masih Daneshvari Hospital as a designated hospital for COVID-19 between Feb 19 and Apr 30, 2020. Multivariate analysis was done to determine the impact of IFN-β1-a on outcome and all-cause mortality. 152 cases in IFN-β1-a group and 304 cases as control group were included. IFN-β1-a group stayed at hospital longer and required noninvasive ventilation more than control group (13 vs. 6 days, p = 0.001) and (34% vs. 24%, p = 0.04), respectively. During treatment, 57 (12.5%) patients died. The death rate in case and control groups was 11% and 13% respectively. In multivariate analysis, not receiving IFN-β1-a (HR 5.12, 95% CI: 2.77-9.45), comorbidity (HR 2.28, 95% CI: 1.13-4.60) and noninvasive ventilation (HR 2.77, 95% CI: 1.56-4.93) remained significantly associated with all-cause mortality. In this study, risk of death decreased by using IFN-β1-a in COVID-19 patients. More clinical study will be necessary to measure efficacy of IFN-β1-a in COVID-19 treatment.
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http://dx.doi.org/10.1016/j.intimp.2020.107329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762801PMC
March 2021

Changed pattern of hospital admission in stroke during COVID-19 pandemic period in Iran: a retrospective study.

Neurol Sci 2021 Feb 4;42(2):445-453. Epub 2021 Jan 4.

Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Some previous reports have shown a reduced number of admission in stroke cases during the coronavirus disease 2019 (COVID-19) pandemic period. The present study aimed to investigate this changing pattern and the potential causes behind it at an academic neurology and neurosurgery center in Iran.

Methods: Patients admitted to our center with the diagnosis of ischemic and hemorrhagic stroke, between March 1, 2019, Jun 1, 2019, and the similar 3-month period in 2020 (COVID-19 pandemic period), were compared in terms of clinical characteristics and outcome. Poisson regression was also conducted to assess the correlation between daily admissions and the COVID-19 pandemic period.

Results: A total of 210 patients with stroke (ischemic and hemorrhagic) in 2019 were compared with 106 patients in 2020. COVID-19 pandemic period was significantly associated with the decline in the number of daily admissions in ischemic stroke (IRR, 0.51 [95% CI, 0.4-0.64]). A significant reduction (P = 0.003) in time from onset to arrival at hospital from median 12 h [IQR, 5-32] in 2019 to median 6 h [IQR, 4-16] in 2020 was found in ischemic stroke cases. National Institute of Health Stroke Scale (NIHSS) was significantly increased (P < 0.001) from median 4 [IQR, 2-7] in 2019 to median 9 [IQR, 4-14] in 2020. Glasgow coma scale (GCS) was significantly decreased from 13.9 (SD, 2) in 2019 to 12.8 (SD, 2.9) in 2020 (P < 0.001).

Conclusions: The present study provided new pieces of evidence regarding the changed pattern of hospital admission in stroke especially the possible reasons for its decline.
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http://dx.doi.org/10.1007/s10072-020-05030-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780589PMC
February 2021

Preoperative Serum Level of Vitamin D is a Possible Protective Factor for Peritumoral Brain Edema of Meningioma: A Cross Sectional Study.

Nutr Cancer 2020 Dec 17:1-7. Epub 2020 Dec 17.

Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Meningioma is associated with the development of vasogenic edema defined as disrupted blood brain barrier. Vitamin D3 through its own nuclear receptor can regulate the expression of many effective agents on the integrity of the blood brain barrier. This study aimed to investigate the association between preoperative serum levels of 25(OH)D and peritumoral brain edema in patients with meningioma. One hundred and twelve patients with meningioma completed the study. Serum 25(OH)D levels assessment and magnetic resonance imaging (MRI) were done for all patients at the beginning of the study. The percentage of edema index (EI) was used to estimate the extent of peritumoral brain edema through preoperative MRI. The median serum level of 25(OH)D in the patients with the percentage of EI < 100% was significantly higher than those with > 100% (65.58 vs. 37.33,  < 0.001). The median percentage of EI was 24.9. Preoperative serum levels of 25(OH)D had an inverse and significant correlation with the percentage of EI as by increasing each 1 ng/mL of serum 25(OH)D, EI was decreased approximately 4% (95% CI; -5.984 to -1.952,  < 0.001). Vitamin D may be a protective factor for peritumoral brain edema of meningioma.
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http://dx.doi.org/10.1080/01635581.2020.1861311DOI Listing
December 2020

Clinical Manifestations of Patients with Coronavirus Disease 2019 (COVID-19) in a Referral Center in Iran.

Tanaffos 2020 Nov;19(2):122-128

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Following the recent epidemic of coronavirus disease 2019 (COVID-19) in Wuhan, China, a novel betacoronavirus was isolated from two patients in Iran on February 19, 2020. In this study, we aimed to determine the clinical manifestations and outcomes of the first confirmed cases of COVID-19 infection (n=127).

Materials And Methods: This prospective study was conducted on all COVID-19-suspected cases, admitted to Masih Daneshvari Hospital (a designated hospital for COVID-19), Tehran, Iran, since February 19, 2020. All patients were tested for COVID-19, using reverse transcription-polymerase chain reaction (RT-PCR) assay. Data of confirmed cases, including demographic characteristics, clinical features, and outcomes, were collected and compared between three groups of patients, requiring different types of admission (requiring ICU admission, admission to the general ward, and transfer to ICU).

Results: Of 412 suspected cases, with the mean age of 54.1 years (SD=13.4), 127 (31%) were positive for COVID-19. Following the patients' first visit to the clinic, 115 cases were admitted to the general ward, while ten patients required ICU admission. Due to clinical deterioration in the condition of 25 patients (out of 115 patients), ICU admission was essential. Based on the results, the baseline characteristics of the groups were similar. Patients requiring ICU admission were more likely to have multiorgan involvement (liver involvement, P<0.001; renal involvement, P<0.001; and cardiac involvement, P=0.02), low O saturation (P<0.001), and lymphopenia (P=0.05). During hospital admission, 21 (16.5%) patients died, while the rest (83.5%) were discharged and followed-up until March 26, 2020. Also, the survival rate of patients, who received immunoglobulin, was higher than other patients (60.87% vs. 39.13%).

Conclusion: The mortality rate of COVID-19 patients was considerable in our study. Based on the present results, this infection can cause multiorgan damage. Therefore, intensive monitoring of these patients needs to be considered.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680520PMC
November 2020

Introducing APOA1 as a key protein in COVID-19 infection: a bioinformatics approach.

Gastroenterol Hepatol Bed Bench 2020 ;13(4):367-373

Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: Introducing possible diagnostic and therapeutic biomarker candidates via the identification of chief dysregulated proteins in COVID-19 patients is the aim of this study.

Background: Molecular studies, especially proteomics, can be considered as suitable approaches for discovering the hidden aspect of the disease.

Methods: Differentially expressed proteins (DEPs) of three patients with demonstrated severe condition (S-COVID-19) were compared to healthy cases by a proteomics study. Cytoscape software and STRING database were used to construct the protein-protein interaction (PPI) network. The central DEPs were identified through topological analysis of the network. ClueGO+CluePedia were applied to find the biological processes related to the central nodes. MCODE molecular complex detection (MCODE) was used to discover protein complexes.

Results: A total of 242 DEPs from among 256 query ones were included in the network. Centrality analysis of the network assigned 16 hub-bottlenecks, nine of which were presented in the highest-scored protein complex. Ten protein complexes were determined. APOA1 was identified as the protein complex seed, and APP, EGF, and C3 were the top hub-bottlenecks of the network. The results specify that up-regulation of C3 and down-regulation of APOA1 in urine play a role in the stiffness in respiration and, accordingly, the severity of COVID-19. Moreover, dysregulation of APP and APOA1 could both contribute to the possible adverse effects of COVID-19 on the nervous system.

Conclusion: The introduced central proteins of the S-COVID-19 interaction network, particularly APOA1, can be considered as diagnostic and therapeutic targets related to the coronavirus disease after being approved with complementary studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682979PMC
January 2020

Systematic Analysis of Protein-Protein and Gene-Environment Interactions to Decipher the Cognitive Mechanisms of Autism Spectrum Disorder.

Cell Mol Neurobiol 2020 Nov 9. Epub 2020 Nov 9.

Proteomics Research Center, Shahid Beheshti University of Medical Sciences, 19716-53313, Tehran, Iran.

Autism spectrum disorder (ASD), a heterogeneous neurodevelopmental disorder resulting from both genetic and environmental risk factors, is manifested by deficits in cognitive function. Elucidating the cognitive disorder-relevant biological mechanisms may open up promising therapeutic approaches. In this work, we mined ASD cognitive phenotype proteins to construct and analyze protein-protein and gene-environment interaction networks. Incorporating the protein-protein interaction (PPI), human cognition proteins, and connections of autism-cognition proteins enabled us to generate an autism-cognition network (ACN). With the topological analysis of ACN, important proteins, highly clustered modules, and 3-node motifs were identified. Moreover, the impact of environmental exposures in cognitive impairment was investigated through chemicals that target the cognition-related proteins. Functional enrichment analysis of the ACN-associated modules and chemical targets revealed biological processes involved in the cognitive deficits of ASD. Among the 17 identified hub-bottlenecks in the ACN, PSD-95 was recognized as an important protein through analyzing the module and motif interactions. PSD-95 and its interacting partners constructed a cognitive-specific module. This hub-bottleneck interacted with the 89 cognition-related 3-node motifs. The identification of gene-environment interactions indicated that most of the cognitive-related proteins interact with bisphenol A (BPA) and valproic acid (VPA). Moreover, we detected significant expression changes of 56 cognitive-specific genes using four ASD microarray datasets in the GEO database, including GSE28521, GSE26415, GSE18123 and GSE29691. Our outcomes suggest future endeavors for dissecting the PSD-95 function in ASD and evaluating the various environmental conditions to discover possible mechanisms of the different levels of cognitive impairment.
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http://dx.doi.org/10.1007/s10571-020-00998-wDOI Listing
November 2020

Baseline Characteristics and Associated Factors of Mortality in COVID-19 Patients; an Analysis of 16000 Cases in Tehran, Iran.

Arch Acad Emerg Med 2020 6;8(1):e70. Epub 2020 Sep 6.

School of Traditional Medicine, Traditional Medicine & Materia Medica Research Center Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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Introduction: Given the importance of evidence-based decision-making, this study aimed to evaluate epidemiological and clinical characteristics as well as associate factors of mortality among admitted COVID-19 cases.

Methods: This multicenter, cross-sectional study was conducted on confirmed and suspected COVID-19 cases who were hospitalized in 19 public hospitals affiliated to Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran, between February 19 and May 12, 2020. Epidemiological and clinical characteristics of the infected cases were compared between the deceased and survivors after discharge. Case fatality rates (CFRs) were calculated across all study variables. Single and multiple logistic regressions were used to explore the risk factors associated with COIVD-19 mortality.

Results: Out of the 16035 cases that referred to the hospitals affiliated to SBMU, 16016 patients (99.93% of Confirmed and 99.83% of suspected cases) were hospitalized. 1612 patients died with median hospitalization days of 5 (interquartile range (IQR): 2-9) and 3 (1-7) for confirmed and suspected COVID-19 cases, respectively. The highest death rate was observed among ages>65 (63.4% of confirmed cases, 62.3% of suspected cases) and intensive care unit (ICU)/critical care unit (CCU) patients (62.7% of confirmed cases, 52.2% of suspected cases). Total case fatality rate (CFR) was 10.05% (13.52% and 6.37% among confirmed and suspected cases, respectively). The highest total CFR was observed in patients with age>65 years (25.32%), underlying comorbidities (25.55%), and ICU/CCU patients (41.7%). The highest CFR was reported for patients who had diabetes and cardiovascular diseases (38.46%) as underlying non-communicable diseases (NCDs), and patients with cancer (35.79%).

Conclusion: This study showed a high CFR among suspected and confirmed COVID-19 cases, and highlighted the main associated risk factors including age, sex, underlying NCDs, and ICU/CCU admission affecting survival of COVID-19 patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588000PMC
September 2020

Extracorporeal Hemoperfusion as a Potential Therapeutic Option for Severe COVID-19 patients; a Narrative Review.

Arch Acad Emerg Med 2020 22;8(1):e67. Epub 2020 Aug 22.

Department of Anesthesiology and Critical Care, Qom University of Medical Sciences, Qom, Iran.

The 2019 novel coronavirus (officially known as severe acute respiratory syndrome coronavirus 2, SARS-CoV2) was first found in Wuhan, China. On February 11, 2020, the World Health Organization (WHO) has declared the outbreak of the disease caused by SARS-CoV2, named coronavirus disease 2019 (COVID-19), as an emergency of international concern. Based on the current epidemiological surveys, some COVID-19 patients with severe infection gradually develop impairment of the respiratory system, acute kidney injury (AKI), multiple organ failure, and ultimately, death. Currently, there is no established pharmacotherapy available for COVID-19. As seen in influenza, immune damage mediated by excessive production of inflammatory mediators contributes to high incidence of complications and poor prognosis. Thus, removal or blocking the overproduction of these mediators potentially aids in reducing the deleterious cytokine storm and improving critically ill patients' outcomes. Based on previous experience of blood purification to treat cytokine storm syndrome (CSS) in severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), here we aimed to review the current literature on extracorporeal hemoperfusion as a potential therapeutic option for CSS-associated conditions, with a focus on severe COVID-19.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587998PMC
August 2020

Legal Considerations of COVID-19 Patients' Disposition in Emergency Department; Report of 10 Cases.

Arch Acad Emerg Med 2020 27;8(1):e64. Epub 2020 Jun 27.

Department of Legal Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran.

COVID-19 pandemic is a challenge in the current era. The spread of this viral infection began in Wuhan City in China, and Iran was also one of the countries struggling with it. Considering the nature of this virus and the current pandemic, it is essential that the healthcare system authorities issue a clear and firm law on treating people infected with COVID-19 to prevent the consequences affecting the professional life of physicians and healthcare staff. The current study aimed at evaluating the legal consequences of COVID-19 cases in emergency department (ED). This case series reported 10 patients that filed complaints against medical staff for problems that occurred on arrival, during the hospital stay or discharge in Shohada-ye-Tajrish and Shahid Modarres educational Hospitals, Tehran, Iran. Consultation with forensic medicine department was requested for all patients and the final decision for each case was reported under the title legal considerations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587992PMC
June 2020

Developing "Code of Ethics for Medical Professionals, Medical Council of Islamic Republic of Iran".

Arch Iran Med 2020 10 1;23(10):658-664. Epub 2020 Oct 1.

Immunology and Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: The medical profession has always been an inspiration for human societies throughout its diverse history. This position and historical authority in the field of ethics has had a different and higher status, in such a way that many of the norms of general ethics and professional ethics, especially principles, such as trust, confidentiality and respect for human dignity, have been developed by medical professionals. Developing guidelines of general and professional ethics is one of the inherent duties of the Medical Council of the Islamic Republic of Iran (IRIMC) as a professional organization. In this regard, the Supreme Council of IRIMC has approved the "Code of Ethics for Medical Professionals" and, in accordance with its legal authority, has annexed it to the disciplinary regulations of IRIMC.

Methods: A draft document, the result of extensive literature review, was discussed in 27 expert panel meetings and after receiving and endorsing the stakeholders' point of view, was approved by the IRIMC Supreme Council.

Results: The first edition of "Code of Ethics for Medical Professionals, Medical Council of Islamic Republic of Iran" was developed on July 6, 2017 by the Supreme Council of IRIMC. The guideline was set to take effect one year after its enactment. The first edition was revised and completed and final edition was adopted on August 9, 2018 by IRIMC in 13 chapters and 140 articles (original full text is available in the Supplementary file 1).

Conclusion: According to the approved decision by the Supreme Council of IRIMC on May 10, 2018, the final edition takes effect as of October 7, 2018.
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http://dx.doi.org/10.34172/aim.2020.83DOI Listing
October 2020

Corticosteroids on the Management of Coronavirus Disease 2019 (COVID-19): A Systemic Review and Meta-Analysis.

Iran J Public Health 2020 Aug;49(8):1411-1421

Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: We aimed to examine the available evidence regarding the efficacy and safety of corticosteroids on the management of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV).

Method: An extensive search was conducted in Medline, Embase, and Central databases until the end of March 2020, using keywords related to corticosteroids, COVID-19, SARS-CoV and MERS-CoV. The main outcome was considered to be the mortality rate, length of stay, virus clearance time, symptom improvement, and lung function improvement. The findings are presented as odds ratio (OR) with 95% confidence interval (95% CI).

Results: Fifteen paper compromising 5 studies on COVID-19, 8 studies on SARS-CoV and 2 studies on MERS-CoV were included. One study was clinical trial and the rest were cohort. The analyses showed that corticosteroids were not reduce the mortality rate of COVID-19 (OR=1.08; 95% CI: 0.34 to 3.50) and SARS-CoV (OR=0.77; 95% CI: 0.34 to 1.3) patients, while they were associated with higher mortality rate of patients with MERS-CoV (OR = 2.52; 95% CI: 1.41 to 4.50). Moreover, it appears that corticosteroids administration would not be effective in shortening viral clearance time, length of hospitalization, and duration of relief symptoms following viral severe acute respiratory infections.

Conclusion: There is no evidences that corticosteroids are safe and effective on the treatment of severe acute respiratory infection when COVID-19 disease is suspected. Therefore, corticosteroids prescription in COVID-19 patients should be avoided.
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http://dx.doi.org/10.18502/ijph.v49i8.3863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554375PMC
August 2020

Correlation Between Low-Dose Chest Computed Tomography and RT-PCR Results for the Diagnosis of COVID-19: A Report of 27,824 Cases in Tehran, Iran.

Acad Radiol 2020 Sep 21. Epub 2020 Sep 21.

School of Statistics & Information Technology Management, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Rationale And Objectives: Real-time polymerase chain reaction (RT-PCR) remains the gold standard for confirmation of Coronavirus Disease 2019 (COVID-19) despite having many disadvantages. Here, we investigated the diagnostic performance of chest computed tomography (CT) as an alternative to RT-PCR in patients with clinical suspicion of COVID-19 infection.

Methods: In this descriptive cross-sectional study, 27,824 patients with clinical suspicion of COVID-19 infection who underwent unenhanced low-dose chest CT from 20 February, 2020 to 21 May, 2020 were evaluated. Patients were recruited from seven specifically designated hospitals for patients with COVID-19 infection affiliated to Shahid Beheshti University of Medical Sciences. In each hospital, images were interpreted by two independent radiologists. CT findings were considered as positive/negative for COVID-19 infection based on RSNA diagnostic criteria. Then, the correlation between the number of daily positive chest CT scans and number of daily PCR-confirmed cases and COVID-19-related deaths in Tehran province during this three-month period was assessed. The trends of admission rate and patients with positive CT scans were also evaluated.

Results: A strong positive correlation between the numbers of daily positive CT scans and daily PCR-confirmed COVID-19 cases (r = 0.913, p < 0.001) was observed. Furthermore, in hospitals located in regions with a lower socioeconomic status, the admission rate and number of positive cases within this three-month period was higher as compared to other hospitals.

Conclusion: Low-dose chest CT is a safe, rapid and reliable alternative to RT-PCR for the diagnosis of COVID-19 in high-prevalence regions. In addition, our study provides further evidence for considering patients' socioeconomic status as an important risk factor for COVID-19.
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http://dx.doi.org/10.1016/j.acra.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505583PMC
September 2020

Descriptive Epidemiology of Brain and Central Nervous System Tumours: Results from Iran National Cancer Registry, 2010-2014.

J Cancer Epidemiol 2020 18;2020:3534641. Epub 2020 Sep 18.

Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Central nervous system (CNS) tumours account for only 1-2% of cancer incidence but are a major reason for mortality and morbidity due to malignancies. Recent studies show an increase in the rate of CNS tumours worldwide, especially in developing countries. Moreover, there is significant heterogeneity in epidemiological patterns worldwide. This study is aimed at representing nationwide epidemiology of CNS tumours in Iran.

Methods: Iran National Cancer Registry 2010-2014 data were reviewed for CNS tumours. The epidemiological rates were calculated for both genders and all age groups using the 2011 census information.

Results: Out of 17345 cases, 58.5% were men and 41.5% were women. The mean age was 45.55 years ranging from less than 1 month to 100 years old. Average total age-standardized incidence rate (ASR) was 5.19 for primary tumours. The annual percent change (APC) was 14.23% during the study period. The most frequent site and histology recorded were brain, NOS and diffuse astrocytic, respectively. Geographical distribution showed about five-fold difference in ASRs between different provinces.

Conclusion: The overall ASR calculated was higher than the global rate in 2012 but lower than that of most developed countries, showing an increasing trend which may be due to either advances in diagnosing or risk factor augmentation. The mean age and incident rates were higher than those of previous reports in Iran.
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http://dx.doi.org/10.1155/2020/3534641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520005PMC
September 2020

Recent advances, approaches and challenges in targeting pathways for potential COVID-19 vaccines development.

Immunol Res 2020 12 1;68(6):315-324. Epub 2020 Oct 1.

Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

During the COVID-19 pandemic in a modern era, there is a global consensus on the need for the rapid development of a vaccine against SARS-CoV-2 for effective and sustainable control. Developing these vaccines is fundamental to public health. This urgent need is supported by the scientific explosion in structural and genomic biology that facilitates the urgent development of an ideal COVID-19 vaccine, using new pathways to facilitate its large-scale development, testing, and manufacture. Here, we summarize the types of COVID-19 candidate vaccines, their current stage in early testing in human clinical trials, and the challenges for their implementation.
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http://dx.doi.org/10.1007/s12026-020-09154-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529090PMC
December 2020

Stem Cell-Derived Exosomes as Treatment for Stroke: a Systematic Review.

Stem Cell Rev Rep 2021 Apr;17(2):428-438

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: The therapeutic potential of stem cells may largely be mediated by paracrine factors contained in exosomes released from intracellular endosomes. A systematic review was performed to identify the effects of stem cell-derived exosomes for their ability to induce restorative effects in animal models of stroke.

Methods: PubMed, Scopus, and ISI Web of Science databases were searched for all available articles testing stem cell-derived exosomes as therapeutic interventions in animal models of stroke until April 2020. The STAIR scale was used to assess the quality of the included studies.

Results: A total of 994 published articles were identified in the systematic search. After screening for eligibility, a total of 16 datasets were included. Type of cerebral ischemia was transient in majority studies and most studies used rat or mice adipose tissue-derived stem cells/bone marrow-derived stem cells. Eight studies indicated improved functional recovery while 8 were able to show reduced infarct volume as a result of exosome therapy. The beneficial effects were mainly attributed to reduced inflammation and oxidative stress, enhanced neurogenesis, angiogenesis, and neurite remodeling. Also, 4 studies demonstrated that exosomes hold great promise as an endogenous drug delivery nano-system.

Conclusion: In preclinical studies, use of stem cell-derived exosomes is strongly associated with improved neurological recovery and reduced brain infarct volume following stroke. Improved preclinical study quality in terms of treatment allocation reporting, randomization and blinding will accelerate needed progress towards clinical trials that should assess feasibility and safety of this therapeutic approach in humans. Graphical abstract.
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http://dx.doi.org/10.1007/s12015-020-10024-7DOI Listing
April 2021

The Deadly Cost of Ignorance: The Risk of Second Wave of COVID-19.

Asia Pac J Public Health 2020 11 10;32(8):511-512. Epub 2020 Sep 10.

Advanced diagnostic and interventional radiology research center, Tehran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.1177/1010539520957809DOI Listing
November 2020

Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran.

Tohoku J Exp Med 2020 09;252(1):73-84

Hematology, Oncology, and Hematopoietic Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Science.

The Coronavirus Disease 2019 (COVID-19) pandemic has killed many people worldwide since December 2019, and Iran has been among the most affected countries. In this retrospective study, we aimed to determine the prognostic factors associated with mortality in COVID-19 patients by analyzing 396 survived and 63 non-survived patients in Shahid Modarres Hospital, Tehran, Iran, from January 30 until April 5, 2020. As the results, the BMI > 35 (p = 0.0003), lung cancer (p = 0.007), chronic kidney disease (p = 0.002), Immunocompromised condition (p = 0.003), and diabetes (p = 0.018) were more frequently observed in the expired group. The history of statins use was more common in the discharged group (p = 0.002), while there was no significant difference in the drug history of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, nonsteroidal anti-inflammatory drugs, aspirin, and/or steroids, and in the past-year influenza vaccination. Multivariable regression demonstrated rising odds of in-hospital death related with age (odds ratio (OR) = 1.055, p = 0.002), levels of C-reactive protein (CRP) (OR = 2.915, p < 0.001), creatinine (OR = 1.740, p = 0.023), lymphocyte count (OR = 0.999, p = 0.008), and magnesium level (OR = 0.032, p < 0.001) on admission. In conclusion, the patients with older age and higher BMI with lymphopenia, hypomagnesemia, elevated CRP and/or raised creatinine on admission are at higher risk of mortality due to the COVID-19 infection, which requires the physicians to use timely and strong therapeutic measures for such patients.
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http://dx.doi.org/10.1620/tjem.252.73DOI Listing
September 2020

The effect of the "segment" of spinal cord injury on the activity of the nucleotide-binding domain-like receptor protein 3 inflammasome and response to hormonal therapy.

Cell Biochem Funct 2021 Mar 7;39(2):267-276. Epub 2020 Sep 7.

Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Spinal cord injury (SCI) is a common devastating condition that causes neuronal loss and dysfunction. Neuroinflammation takes cardinal roles in the pathogenesis of SCI, and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome is a mediator of inflammatory reactions occurring in SCI patients. The present study was designed to survey possible relation between thoracic segments whereby injury occurs with the activity of NLRP3 inflammasome complex, and to find the influence of hormonal therapy on the outcomes. Adult male Wistar rats underwent contusion SCI model at three different thoracic segments T1, T6 and T12, then receiving subcutaneous injection of either 10 mg/kg melatonin or 25 μg/kg 17-β estradiol (E2) every 12 hours until 72 hours post-SCI. Inflammasome activity was assessed before and at the end of hormonal therapy. SCI rats showed decreased locomotor activity and myelination, and increased activity of the NLRP3, apoptosis-associated speck-like protein (ASC) and caspase-1 at gene and protein levels. Release of interleukins (ILs) 18 and 1β was also augmented after SCI (P < 0.0.5). Hormonal therapy was most effective for targeting mRNA activity at T6 segment. Treatment with either melatonin or E2 caused a decrease in the protein activity of NLRP3 inflammasome at all segments (P < 0.0.5), except for T6 that NLRP3 protein had no response to melatonin. IL-1β showed decreased activity in response to hormonal therapy at all segments, whilst IL-18 protein had no change at T1 segment. It is understood that although no alteration in the activity of NLRP3 was found for SCI at different segments, the response to hormonal therapy was influenced by segment. SIGNIFICANCE OF THE STUDY: From our results, the NLRP3 inflammasome activity is not influenced by segment, but there are differences in the effect of hormonal therapy on inflammasome activity at different segments in response to melatonin or E2. These findings also provide the beneficial effects of melatonin or E2 on inflammation caused by spinal cord injury in different thoracic segments. Finally, these data can have therapeutic importance for hormone therapy of spinal cord injury.
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http://dx.doi.org/10.1002/cbf.3574DOI Listing
March 2021

Neuroprotective Properties of Photobiomodulation in Retinal Regeneration in Rats: Perspectives From Interaction Levels.

J Lasers Med Sci 2020 21;11(3):280-286. Epub 2020 Jun 21.

Department of Psychosomatic, Taleghani Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Photobiomodulation (PBM) is known as low-level laser (or light) therapy and is applied in different fields of medicine. However, it is required that its molecular and cellular mechanism be investigated. This study aims to assess the neuroprotective properties of PBM in the rat retina. GSE22818 was downloaded from Gene Expression Omnibus (GEO) and the regulation of the significant differentially expressed genes (DEGs) which are produced by light damage in the rat retina by the pretreatment of PBM application was assessed via network analysis and gene ontology enrichment. The 78 produced DEGs by light-damage in the rat retina were protected via PBM pretreatment action. Among these determined DEGs, 53 individuals were included in the main connected component of the constructed protein-protein interaction (PPI) network. Ccl2, Icam1, Cxcl10, Timp1, and Fos were determined as hub nodes. Eight clusters including 26 regulated biochemical pathways by PBM pretreatment were identified. The critical DEGs based on the action maps were introduced. The finding indicates that PBM treatment protects rat retina against light damage via the prevention of Fos, Ccl2, Icam1, Cxcl10, and Myc dysregulation.
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http://dx.doi.org/10.34172/jlms.2020.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369552PMC
June 2020

Assessment of the Microbiome Role in Skin Protection Against UV Irradiation Via Network Analysis.

J Lasers Med Sci 2020 21;11(3):238-242. Epub 2020 Jun 21.

Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Diverse microbiotas which have some contributions to gene expression reside in human skin. To identify the protective role of the skin microbiome against UV exposure, proteinprotein interaction (PPI) network analysis is used to assessment gene expression alteration. A microarray dataset, GEO accession number GSE117359, was considered in this respect. Differential expressed genes (DEGs) in the germ-free (GF) and specific pathogen-free (SPF) groups are analyzed by GEO2R. The top significant DEGs were assigned for network analysis via Cytoscape 3.7.2 and its applications. A total of 28 genes were identified as significant DEGs and the centrality analysis of the network indicated that only one of the seven hub-bottlenecks was from queried genes. The gene ontology analysis of Il6, Cxcl2, Cxcl1, TNF, Il10, Cxcl10, and Mmp9 showed that the crucial genes were highly enriched in the immune system. The skin microbiome plays a significant role in the protection of skin against UV irradiation and the role of TNF and IL6 is prominent in this regard.
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http://dx.doi.org/10.34172/jlms.2020.40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369546PMC
June 2020

Management of Spine Trauma in COVID-19 Pandemic: A Preliminary Report.

Arch Bone Jt Surg 2020 Apr;8(Suppl 1):270-276

Functional Neurosurgery Research Center, Shohadaye Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: COVID-19 was first identified in Iran in February 2020 and since then it spread rapidly through all over the country and soon after that it was reported as a pandemic. The current study presents a preliminary report of spine trauma management during COVID-19 pandemic.

Methods: A cross sectional study was designed to evaluate patients admitted for vertebral fractures with diagnosis of COVID-19 infection on February and March 2020. Analysis was made based on clinical and laboratory data along with the imaging findings from chest HRCT.

Results: Seven patients with spine trauma including five males and two females ranging from 14 to 59 years were diagnosed for COVID-19 infection through CT-scan findings. Except one, all other patients were asymptomatic for COVID-19 at the time of admission. In three cases the COVID diagnosis was made the day after arrival and in others after 10, 14 and 35 days. Five patients were treated surgically among whom four were admitted to ICU soon after the surgery. The mean ICU stay for operated patients were eight days and the mean hospital stay was 22.6 days.

Conclusion: Proper diagnosis of COVID-19 is the keystone to protect both patients and health care providers. During the pandemic all admitted patients should be screened for COVID-19 infection. Unnecessary procedures for spine trauma patients should be avoided in order to reduce complications related to surgery and to preserve ICU beds.
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http://dx.doi.org/10.22038/abjs.2020.47882.2368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296594PMC
April 2020

The expression level of cannabinoid receptors type 1 and 2 in the different types of astrocytomas.

Mol Biol Rep 2020 Jul 4;47(7):5461-5467. Epub 2020 Jul 4.

Functional Neurosurgery Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Astrocytomas, the most prevalent primary brain tumors, can be divided by histology and malignancy levels into four following types: pilocytic astrocytoma (grade I), diffuse fibrillary astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma multiforme (grade IV). For high grade astrocytomas (grade III and grade IV), blood vessels formation is considered as the most important property. The distribution of cannabinoid receptors type 1 (CB1) and cannabinoid receptor type 2 (CB2) in blood vessels and tumor tissue of astrocytoma is still controversial. Asrocytoma tissues were collected from 45 patients under the condition of tumor-related neurosurgical operation. The expression of CB1 and CB2 receptors was assessed using immunofluorescence, quantitative real-time RT-PCR and western blotting. The results indicated an increased expression of CB1 receptors in tumor tissue. There was a significant difference in the mount of CB2 receptors in blood vessels. More was observed in the grade III and glioblastoma (grade IV) than astrocytoma of grade II and control. This study suggested that, the expression increase of cannabinoid receptors is an index for astrocytoma malignancy and can be targeted as a therapeutic approach for the inhibition of astrocytoma growth among patients.
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http://dx.doi.org/10.1007/s11033-020-05636-8DOI Listing
July 2020