Cytokine profile and antioxidants status in the moderate and severe COVID-19 patients: a trial of ozone therapy impact as a medicinal supplement.

BACKGROUND: Complementary ozone therapy has been identified as a revolutionary medical technique for a number of goals and ailments. At the present, it has been shown that ozone has medicinal qualities, such as antibacterial, antifungal, and antiparasitic properties. Coronavirus (SARS-CoV-2) is quickly spread over the globe. Cytokine storms and oxidative stress seem to play a substantial role in the most of acute attacks of the disease. The aim of this research was to assess the therapeutic advantages of complementary ozone therapy on the cytokine profile and antioxidant status in COVID-19 patients. METHODS: The statistical sample of this study included two hundred patients with COVID-19. One hundred COVID-19 patients (treatment group) received 240 ml of the patient's blood and an equal volume of O2/O3 gas at a concentration of 35-50 µg/ml daily, which gradually increased in concentration, and were kept for 5-10 days and one hundred patients (control group) received standard treatment. The secretion levels of IL-6, TNF-α, IL-1ß, IL-10 cytokines, SOD, CAT and GPx were compared between control patients (standard treatment) and standard treatment plus intervention (ozone) before and after treatment. RESULTS: The findings indicated a significant decrease in the level of IL-6, TNF-α, IL-1ß in group receiving complementary ozone therapy in compared with control group. Furthermore, a significant increase was found in the level of IL-10 cytokine. Moreover, SOD, CAT and GPx levels revealed a significant increase in complementary ozone therapy group compared to control group. CONCLUSIONS: Our results revealed that complementary ozone therapy can be used as a medicinal complementary therapy to reduce and control inflammatory cytokines and oxidative stress status in patients with COVID-19 as revealed its antioxidant and anti-inflammatory effects.

Comparative proteomic analysis of mustard lung as a complicated disease using systems biology approach.

During Iraq-Iran conflict, chemical weapons, particularly SM gas, were used numerous times, whose aftereffects are still present. This study aimed to compare serum proteome in the chronic ML (n = 10) and HC (n = 10). TMT label-based quantitative proteomics was used to examine serums from two groups. Among total significant proteins, 14 proteins were upregulated (log2 ≥ FC 0.5, p 0.05), and 6 proteins were downregulated (log2 ≤ FC - 0.5, p 0.05). By helping PPI network, and EA, 11 main pathways connected to significantly different protein expression levels were discovered, including inflammatory and cell adhesion signaling pathways. It may be deduced that the wounded organs of exposed individuals experience poor repair cycles of cell degeneration and regeneration because certain repair signals were elevated while other structural and adhesion molecules were downregulated. The systems biology approach can help enhance our basic knowledge of biological processes, and contribute to a deeper understanding of pathophysiological mechanisms, as well as the identification of potential biomarkers of disease.

Proteomics analysis of chronic skin injuries caused by mustard gas.

Sulfur mustard (SM) is an alkylating and forming chemical that was widely used by Iraqi forces during the Iran-Iraq wars. One of the target organs of SM is the skin. Understanding the mechanisms involved in the pathogenesis of SM may help better identify complications and find appropriate treatments. The current study collected ten SM-exposed patients with long-term skin complications and ten healthy individuals. Proteomics experiments were performed using the high-efficiency TMT10X method to evaluate the skin protein profile, and statistical bioinformatics methods were used to identify the differentially expressed proteins. One hundred twenty-nine proteins had different expressions between the two groups. Of these 129 proteins, 94 proteins had increased expression in veterans' skins, while the remaining 35 had decreased expression. The hub genes included RPS15, ACTN1, FLNA, HP, SDHC, and RPL29, and three modules were extracted from the PPI network analysis. Skin SM exposure can lead to oxidative stress, inflammation, apoptosis, and cell proliferation.

Tear proteomics analysis of patient suffered from delayed mustard gas keratopathy.

Understanding the molecular and cellular mechanisms involved in the pathogenesis of ocular injured induced by mustard gas can help better identify complications and discover appropriate therapies. This study aimed to analyze the proteomics of tears of chemical warfare victims with mustard gas ocular injuries and compare it with healthy individuals. In this case-control research, 10 mustard gas victims with long-term ocular difficulties (Chronic) were included in the patient group, while 10 healthy persons who were age and sex matched to the patients were included in the control group. Schirmer strips were used to collect the tears of the participants. Proteomics experiments were performed using the high-efficiency TMT10X method to evaluate the tear protein profile, and statistical bioinformatics methods were used to identify the differently expressed proteins. 24 proteins had different expressions between the two groups. Among these 24 proteins, 8 proteins had increased expression in veterans' tears, while the remaining 16 proteins had decreased expression. Reactome pathways were used to look at proteins with various expressions, and 13 proteins were found to be engaged in the immune system, 9 of which were effective in the innate immune system, and 5 proteins were effective in the complement cascade. Ocular mustard gas exposure may cause a compromised immune system on the eye's surface, exposing the cornea to external and endogenous infections, and eventually causing corneal opacity and reduced vision.

Simultaneous determination of BoNT/A and /E using an electrochemical sandwich immunoassay based on the nanomagnetic immunosensing platform.

Developing new ultrasensitive assays for the detection of the presence, and determination of the serotype of the most poisonous material known i.e. botulinum neurotoxin (BoNT) is vital to human health and the wellbeing of the surrounding environment. Here, an electrochemical sandwich immunoassay with high sensitivity is adopted to achieve simultaneous determination of BoNT serotypes A and E based on polystyrene@polydopamine/Cd2+ and Ag nanoparticles acting as monoclonal antibody labels. Two well-separated peaks with strong electrochemical signals are generated by the labels, allowing for the simultaneous detection of two analytes existing on the electrode. To obtain well-oriented polyclonal antibodies immobilization, boronic acid is directly attached to the magnetic core/metal-organic framework (MOF) shell nanoagent surfaces without the requirement of a long and flexible spacer. Accordingly, it is possible to directly detect the metal ion labels through square wave voltammetry without the metal pre-concentration step. This results in distinct and well-defined voltammetric peaks, pertaining to each sandwich-type immunocomplexes. The limits of detection of BoNT/A and BoNT/E analyses were found to be 0.04 and 0.16 pg mL-1 with the linear dynamic ranges of 0.1-1000 and 0.5-1000 pg mL-1, respectively. Based on the obtained results, this immunosensor has the wide linear ranges, while also exhibiting low limits of detection along with good stability and reproducibility.

Prediction of Genes Involved in Lung Cancer with a Systems Biology Approach Based on Comprehensive Gene Information.

Over the past few years, hundreds of genes have been reported in relation to lung cancer. Systems biology studies can help validate this association and find the most valid genes to use in the diagnosis and treatment. We reviewed the candidate genes for lung cancer in 120 published articles from September 1, 1993, to September 1, 2020. We obtained 134 up- and 36 downregulated genes for lung cancer in this article. The genes extracted from the articles were imported to Search Tool for the Retrieval of Interacting genes/proteins (STRING) to construct the protein-protein interaction (PPI) Network and pathway enrichment. GO ontology and Reactome databases were used for describing the genes, average length of survival, and constructing networks. Then, the ClusterONE plugin of Cytoscape software was used to analyze and cluster networks. Hubs and bottleneck nodes were defined based on their degree and betweenness. Common genes between the ClusterONE plugin and network analysis consisted of seven genes (BRCA1-TP53-CASP3-PLK1-VEGFA-MDM2-CCNB1 and PLK1), and two genes (PLK1 and TYMS) were selected as survival factors. Our drug-gene network showed that CASP3, BRCA1, TP53, VEGFA, and MDM2 are common genes that are involved in this network. Also, among the drugs recognized in the drug-gene network, five drugs such as paclitaxel, oxaliplatin, carboplatin, irinotecan, and cisplatin were examined in different studies. It seems that these seven genes, with further studies and confirmatory tests, could be potential markers for lung cancer, especially PLK1 that has a significant effect on the survival of patients. We provide the novel genes into the pathogenesis of lung cancer, and we introduced new potential biomarkers for this malignancy.

Review of proteomics approach to eye diseases affecting the anterior segment.

Visual impairment and blindness is a major health burden worldwide, and major ocular diseases causing visual impairment pertain to the anterior segment of the eye. Anterior segment ocular diseases are common, yet complex entities. Although many treatment options and surgical techniques are available for these ailments, the underlying cause and pathogenesis is still unclear. Finding ways to fundamentally treat these patients and rectify the underlying dysregulations leading to the disease may help cure patients completely without major complications. Proteomics approaches are a novel way to distinguish dysregulated proteins in a variety of biological tissues in a hypothesis-free manner, thus helping to find the responsible pathways leading to a certain disease. The aim of the current study is to review the available knowledge in scientific literature regarding the proteomics studies done on anterior segment eye diseases and suggest potential clinical implications to exploit the results of these studies. SIGNIFICANCE: Anterior segment ocular diseases are responsible for a major proportion of visual impairment and blindness worldwide. Although ophthalmologists have several treatment options that can alleviate or control the progression of these diseases, no definite cure is available for most of them. Moreover, because these diseases are progressive, prompt diagnosis is of utmost important. Proteomics studies enable us to identify and quantify the dysregulated proteins in a biological specimen in a hypothesis-free manner. Understanding the dysregulated protein pathways shines a light on the pathogenesis of the disease. Moreover, these dysregulated proteins may act as biomarkers to help in diagnosis and treatment follow-up. Hence, in this article we sought out to review the available scientific literature regarding the proteomics studies of anterior segment ocular diseases and to identify potential applications of proteomic studies in clinic.

Is the Inflammasome Pathway Active in the Peripheral Blood of Sulfur Mustard-exposed Patients?

The mustard lung is a late consequence of exposure to sulfur mustard (SM) in veterans who had participated in the Iraq-Iran war. Three mechanisms are contributed in the pathogenesis of mustard lung including oxidative stress, protease-antiprotease imbalance, and dysregulated immune response. In the context of the immune response, the role of the inflammasome complex and their inflammatory cytokines are important. This study aims to investigate the inflammasome pathway and their inflammatory cytokine (i.e IL-1 and IL-18) in the peripheral blood of mustard lung patients as well as chronic obstructive pulmonary disease (COPD) patients. This research was conducted as a cross-sectional analytical study on 15 SM patients and was compared with 15 COPD patients and 15 healthy controls. The real-time polymerase chain reaction was used to assess gene expression levels of inflammasome components (NLRP1, NLRP3, NLRC4, and ASC), inflammatory cytokines (IL-1ß, IL-18, and IL-1ßR), and IL-37 as an anti-inflammatory cytokine. Finally, the data were analyzed by SPSS version 21 software. The gene expression level of molecules involved in inflammasome pathway showed a slight increase in the peripheral blood of SM and COPD patients compared to the control group. However, this difference was not statistically significant. Only IL-37 and NLRP1 had a significant increase in mustard lung and COPD patients; compared to healthy controls (p<0.05). Due to the normal expression of genes involved in the inflammasome pathway, it can be stated that the inflammasome pathway is not active in the blood of mustard lung patients.

Mitigation of Systemic Oxidative Stress by Curcuminoids in Osteoarthritis: Results of a Randomized Controlled Trial.

Oxidative stress is implicated in the pathogenesis of osteoarthritis. Curcuminoids are natural polyphenols with strong antioxidant capacity and may thus be helpful in the treatment of osteoarthritis. The present randomized double-blind placebo-controlled trial investigated the efficacy of curcuminoids in reducing systemic oxidative burden in patients suffering from knee osteoarthritis. Forty patients with mild-to-moderate primary knee osteoarthritis were given curcuminoid capsules (1500 mg/day in 3 divided doses; n = 19) or matched placebo capsules (n = 21) for a period of 6 weeks. Curcuminoids were co-administered with piperine (15 mg/day) in order to improve the bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of reduced glutathione (GSH) and malonedialdehyde (MDA) were determined spectrophotometrically at baseline and at the end of the treatment period in both groups. Serum activities of SOD as well as GSH and MDA concentrations were comparable between the study groups at baseline (p > 0.05). There was a significant elevation in serum SOD activities (mean change: 2.94 ± 3.73 vs. -0.38 ± 1.33; p < 0.001), a borderline significant elevation in GSH concentrations (mean change: 1.39 ± 2.78 vs. -0.02 ± 1.62; p = 0.064) and a significant reduction in MDA concentrations (mean change: -5.26 ± 4.46 vs. -2.49 ± 3.81; p = 0.044) in the curcuminoids compared with the placebo group. Changes in serum activities of SOD and concentrations of GSH and MDA during the course of trial were significantly correlated. Short-term supplementation with curcuminoids attenuates systemic oxidative stress in patients with osteoarthritis. These antioxidant effects may account for the reported therapeutic effects of curcuminoids in relieving osteoarthritis symptoms.

Serum Metabolomic Profiling of Sulphur Mustard-Exposed Individuals Using (1)H Nuclear Magnetic Resonance Spectroscopy.

Sulphur mustard is an alkylating agent that reacts with different cellular components, causing acute and delayed complications that may remain for decades after exposure. This study aimed to identify differentially expressed metabolites between mustard-exposed individuals suffering from chronic complications compared with unexposed individuals as the control group. Serum samples were obtained from 15 mustard-exposed individuals and 15 apparently healthy unexposed individuals. Metabolomic profiling was performed using (1)H nuclear magnetic resonance spectroscopy, and analyses were carried out using Chenomex and MATLAB softwares. Metabolites were identified using Human Metabolome Database, and the main metabolic pathways were identified using MetaboAnalyst software. Chemometric analysis of serum samples identified 11 differentially expressed metabolites between mustard-exposed and unexposed groups. The main pathways that were influenced by sulphur mustard exposure were related to vitamin B6 (down-regulation), bile acid (up-regulation) and tryptophan (down-regulation) metabolism. Metabolism of vitamin B6, bile acids and tryptophan are the most severely impaired pathways in individuals suffering from chronic mustard-induced complications. These findings may find implications in the monitoring of exposed patients and identification of new therapeutic approaches.

Oral health status among Iranian veterans exposed to sulfur mustard: A case-control study.

BACKGROUND: Sulfur mustard (SM) is a chemical warfare agent that has been repeatedly used since World War I. SM has chronic and deleterious effects on different body organs such as lungs, skin and eyes. OBJECTIVES: To determine dental and oral health status of chemical victims of SM who were exposed to SM during the Iraqi-Iran war. MATERIAL AND METHODS: In this case-control study, 100 male subjects exposed to SM were chosen as cases, and 100 non-exposed volunteers were chosen as controls. These groups were selected randomly according to their referral number, and were matched regarding age. Collection of information was performed using Oral Health Assessment Form designed by the World Health Organization. Quantitative and qualitative data were compared between the groups using independent samples t-test and Chi-square test, respectively. RESULTS: There was a significant difference between the case and control groups with respect to the frequencies of oral candidiasis, pharyngeal erythema and/or hyperplasia, hairy tongue and reflux disease, being higher in the former group. There was also a positive association between the frequency of candidiasis and the percentage of disability; pharyngeal erythema and/or hyperplasia and use of salmeterol spray; and between hairy tongue and antibiotic use in the case group. CONCLUSIONS: Exposure to SM and the use of drugs for controlling long-term complications does not increase the risk of tooth decay, tooth loss, and intra and/or extra oral lesions in patients, but may be associated with increased incidence of oral candidiasis, pharyngeal erythema and/or hyperplasia, hairy tongue and reflux disease.samples of oral precancerous and cancerous lesions to test sensitivity and specificity and thus validate the clinical applicability of fluorescence imaging in (pre)cancerous diagnostics. Key words:Sulfur mustard, oral health, candidiasis.

Comparative proteome analysis of peripheral neutrophils from sulfur mustard-exposed and COPD patients.

Respiratory disorders in sulfur mustard (SM)-exposed and chronic obstructive pulmonary disease (COPD) patients are mostly associated with neutrophilic inflammation, severe airflow limitation, and oxidative stress. The objective of this study was to establish whether neutrophil (PMN) proteomes in these diseases were similar or differed. Blood neutrophil proteomes from healthy, SM-exposed, and COPD subjects were analyzed using two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF MS). Elastase activity was determined kinetically. The results showed that levels of S100 calcium-binding protein (CBP) A12, S100 CBP A8, glyceraldehyde-3-phosphate dehy-drogenase, superoxide dismutase, and protein disulfide isomerase proteins - as well as elastase activity - were significantly increased in PMN from 'diseased' hosts compared to in cells from healthy controls. In contrast, coactosin-like protein, RhoGDP dissociation inhibitor, and actin isoforms were significantly decreased in diseased subjects' PMN compared to PMN of healthy controls. Moreover, serpin B1 and coronin-1A were expressed only in PMN of the healthy subjects. Lastly, S100 CBP A9, endoplasmic reticulum (ER)-60 protease, and glutathione-S-transferase isoforms were differentially expressed in the cells from the SM-exposed and COPD subjects. These results show that serpin B1, an efficient inhibitor of neutrophil serine proteases, was not detectable, and elastase activity significantly increased in PMN from both SM-exposed and COPD patients. It seems that, apart from inflammation and oxidative stress, a protease:anti-protease imbalance exists within PMN of both COPD and SM-exposed patients.

Effects of supplementation with Heracleum persicum fruit extract on serum lipids in patients undergoing coronary angiography: a pilot trial.

Heracleum persicum Desf. Ex Fischer (Apiaceae) is a native medicinal plant in the Iranian traditional medicine and also a safe and common dietary spice. The present pilot study aimed to investigate the impact of supplementation with H. persicum fruits on serum lipid concentrations in a group of patients with minimal coronary artery disease. Subjects who were diagnosed with <50% luminal narrowing in any of the major coronary arteries in coronary angiography were recruited for this trial and were randomized to receive either H. persicum hydroalcoholic fruit extract (n=15; 300 mg/day) or placebo (n=12) for a period of 6 months. Serum concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured at baseline and at the end of study. No significant difference in concentrations of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol was observed between H. persicum extract and placebo groups (p>0.05). However, serum triglycerides levels were reduced after H. persicum extract supplementation in a borderline significant manner (p=0.063). Short-term supplementation with H. persicum fruit extract might be used as an adjunctive treatment for patients with hypertriglyceridemia.

Effect of recombinant human IFNγ in the treatment of chronic pulmonary complications due to sulfur mustard intoxication.

Pulmonary problems are among the most common chronic complications of sulfur mustard (SM) intoxication and adversely affect patients' quality-of-life. The present trial investigated the impact of immunotherapy with interferon (IFN)-γ on quality-of-life, respiratory symptoms, and circulating immunologic and oxidative parameters in patients suffering from chronic SM-induced complications. Patients (n = 15) were administered IFNγ (100 µg) every other day for a period of 6 months. Assessment of quality-of-life [using St. George respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) indices], the severity and frequency of respiratory symptoms, and serum levels of immunologic [including interleukin (IL)-2, IL-4, IL-6, IL-10, IFNγ, calcitonin gene related peptide (CGRP), matrix metallopeptidase (MMP)-9, and tumor necrosis factor (TNF)-α], oxidative stress [malondialdehyde (MDA) as well as total and reduced glutathione, and catalase and superoxide dismutase (SOD) activity], and fibrogenic [transforming growth factor (TGF)-ß] parameters were performed at baseline and at trial end. The results indicated that IFNγ therapy is associated with improvements in SGRQ (p < 0.001) and CAT (p < 0.001) scores, decreased severity of cough (p = 0.001), dyspnea (p < 0.001), and morning dyspnea (p < 0.001), reduced frequency of sputum production (p < 0.001) and hemoptysis (p < 0.001), and elevated FEV1 (p = 0.065). Serum levels of IL-4 (p < 0.001), IL-6 (p < 0.001), IL-10 (p < 0.001), CGRP (p < 0.001), MMP-9 (p = 0.001), TNFα (p < 0.001), TGFß (p < 0.001) and MDA (p = 0.001) were decreased while those of IL-2 (p < 0.001), IFNγ (p < 0.001), and both total (p = 0.005) and reduced glutathione (p = 0.061) increased by the end of the trial. It was concluded that IFNγ has favorable effects on the quality-of-life and alleviates respiratory symptoms in patients suffering from chronic SM-induced pulmonary complications. A modulation of cytokines and oxidative stress appears responsible for the clinical efficacy of IFNγ.

Investigation of the effects of Chlorella vulgaris supplementation on the modulation of oxidative stress in apparently healthy smokers.

BACKGROUND: Smoking is among the established yet modifiable risk factors for cancers, cardiovascular diseases, and pulmonary disorders. Oxidative stress has been proposed as a key mechanism mediating the deleterious consequences of smoking. The present study evaluated the effect of supplementation with Chlorella vulgaris, a nutrient and bioactive green microalgae with proven antioxidant capacity, on the burden of oxidative stress in Iranian smokers. METHODS: Thirty-eight smokers (mean age: 37.11 +/- 1.69 years; females: 18.4%) were administered C. vulgaris extract (3600 mg/day) for a period of 6 weeks. Fasted serum samples collected at baseline and after the completion of study were analyzed for the concentrations of vitamin C, vitamin E, glutathione, and malonedialdehyde (MDA) as well as activities of superoxide dismutase, glutathione peroxidase, and catalase. Total antioxidant capacity of serum was also determined by the ability of serum to inhibit the formation of ferryl myoglobin radical species. RESULTS: Six-week supplementation with C. vulgaris extract in smokers was associated with marked elevation of all assessed serum antioxidant measures (p < 0.001) and significant reduction of MDA levels (p = 0.002). After gender segregation, a similar pattern of changes was observed for both male and female subjects apart from lack of significant change in serum vitamin E status in females. Although the magnitude of change in serum vitamin E was significantly greater in males compared to females (p = 0.014), there was no significant change in the magnitude of changes for other assessed parameters between the genders. CONCLUSIONS: Supplementation with C. vulgaris extract significantly improves antioxidant status and attenuates lipid peroxidation in chronic cigarette smokers. Hence, C. vulgaris might prevent the disease burden and mortality rate associated with smoking.

A randomized controlled trial on the anti-inflammatory effects of curcumin in patients with chronic sulphur mustard-induced cutaneous complications.

BACKGROUND: Chronic cutaneous complications such as pruritus are among the very frequent complaints of sulphur mustard (SM)-exposed patients. The present trial investigated the impact of curcumin on serum inflammatory biomarkers and their association with pruritus severity and quality of life (QoL). METHODS: This was a randomized, double-blind trial among 96 male Iranian veterans (age 37-59 y) who were suffering from chronic SM-induced pruritic skin lesions. Patients were randomly assigned to curcumin (1 g/d, n = 46) or placebo (n = 50) for four weeks. Serum concentrations of interleukins 6 (IL-6) and 8 (IL-8) together with high-sensitivity C-reactive protein (hs-CRP) and calcitonin gene-related peptide (CGRP) were measured at baseline and at the end of the trial. Assessment of pruritus severity was performed using the pruritus score and QoL using the Dermatology Life Quality Index (DLQI). RESULTS: Serum IL-8 and hs-CRP were significantly reduced in both groups but the magnitude of reduction was greater in the curcumin group (P < 0.001). Serum CGRP was only decreased in the curcumin group (P < 0.001). No significant change was observed in serum IL-6. There were significant correlations between CGRP and IL-6 changes (P = 0.011) and between DLQI and IL-8 changes (P = 0.026) in the curcumin group. In the curcumin group, changes in serum IL-8 concentrations were found as the significant predictor of DLQI scores (P = 0.026) but none of the independent variables could predict pruritus scores. CONCLUSIONS: Curcumin supplementation effectively mitigates inflammation in patients suffering from chronic SM-induced cutaneous complications. This anti-inflammatory effect might account for the observed pruritus alleviation and QoL improvement by this phytochemical.

Tear total protein analysis in patients with late sulfur mustard-induced ocular complications: a cross-sectional study.

BACKGROUND: Eyes are the most sensitive organs to sulfur mustard (SM). Late ocular complications have been reported even 15-20 years post-exposure. To date, no study has investigated the composition of tear proteins in tear samples of SM-intoxicated patients. METHODS: Total protein content as well as concentrations of vascular endothelial growth factor (VEGF), calcitonin gene related peptide (CGRP) and substance P were measured in unstimulated tears of chemically-injured patients who suffer from late ocular complications of SM. These levels were compared to corresponding values obtained from tears of healthy control subjects. The concentration of total proteins was measured using the Bradford method and those of VEGF, CGRP and substance P by ELISA. RESULTS: Total protein concentration was significantly lower in tears of the SM compared to control group (p<0.01). In contrast, tear samples of the SM group had significantly higher VEGF and VEGF/total protein compared to control group (p<0.01). Tear CGRP concentration was found to be lower in the SM vs. control group (p<0.05) but no significant difference in CGRP/total protein was observed (p>0.05). Finally, tear substance P concentrations were not found to be significantly different between the two groups (p>0.05). CONCLUSION: The results of this investigation indicated decreased total protein and CGRP, and elevated VEGF concentration in tears of SM-intoxicated patients who suffer from chronic ocular complications.