Biochemical responses as early and reliable biomarkers of organophosphate and carbamate pesticides intoxication: A systematic literature review.

Inhibition of cholinesterase (ChE) activity has been long considered as the main diagnostic method of organophosphate (OP) and carbamate pesticides poisoning; however, it has been shown that ChE activity may also be altered due to exposure to other non-organophosphorus toxicants and variety of different medical conditions. Hence, to avoid misdiagnosis, we aimed to systematically review available documents to look for additional biomarkers of OP and carbamate poisoning. The electronic databases in addition to Google scholar were searched for eligible articles on March 2022 using "organophosphate," "carbamate," and "biomarker" including all their similar terms. After collecting the relevant documents, the data were extracted and described qualitatively. In total, data of 66 articles from 51 human and 15 animal studies were extracted. Findings demonstrated that enzymes such as ß-glucuronidase, neuropathy target esterase, amylase, and lipase, in addition to hematological indicators such as CBC, CRP, lactate dehydrogenase, and CPK have high sensitivity and accuracy in the diagnosis of OP poisoning. Findings suggest that using various markers for diagnosis of OP intoxication is helpful for appropriate management, and early identifying the patients at risk of death. The suggested biomarkers also help to avoid misdiagnosis of OP poisoning with other similar conditions.

Combination of auraptene and arsenic trioxide induces apoptosis and cellular accumulation in the subG1 phase in adult T-cell leukemia cells.

Objectives: Despite advances in the treatment of adult T-cell leukemia/lymphoma (ATLL), the survival rate of this malignancy remains significantly low. Auraptene (AUR) is a natural coumarin with broad-spectrum anticancer activities. To introduce a more effective therapeutic strategy for ATLL, we investigated the combinatorial effects of AUR and arsenic trioxide (ATO) on MT-2 cells. Materials and Methods: The cells were treated with different concentrations of AUR for 24, 48, and 72 hr, and viability was measured by alamarBlue assay. Then, the combination of AUR (20 µg/ml) and ATO (3 µg/ml) was administrated and the cell cycle was analyzed by PI staining followed by flow cytometry analysis. In addition, the expression of NF-κB (REL-A), CD44, c-MYC, and BMI-1 was evaluated via qPCR. Results: Assessment of cell viability revealed increased toxicity of AUR and ATO when used in combination. Our findings were confirmed by accumulation of cells in the sub G1 phase of the cell cycle and significant down-regulation of NF-κB (REL-A), CD44, c-MYC, and BMI-1. Conclusion: Obtained findings suggest that combinatorial use of AUR and ATO could be considered for designing novel chemotherapy regimens for ATLL.

Current concepts on immunopathogenesis of hepatitis B virus infection.

Hepatitis B virus (HBV) infection is a leading cause of liver damage and hepatic inflammation. Upon infection, effective antiviral responses by CD8+ T cells, CD4+ T cells, Natural killer (NK) cells, and monocytes can lead to partial or complete eradication of the viral infection. To date, many studies have shown that the production of inhibitory cytokines such as Interleukin 10 (IL-10), Transforming growth factor beta (TGF-ß), along with dysfunction of the dendritic cells (DCs), and the absence of efficient innate immune responses could lead to T cell exhaustion, development of persistent infection, and inability to eradicate the viral infection from liver. Understanding the immunopathogenesis of the virus could be useful in providing further insights toward novel strategies in the eradication of HBV infection.

CTLA-4 Gene Haplotypes and the Risk of Chronic Hepatitis C Infection; a Case Control Study.

BACKGROUND: The prevalence of hepatitis C virus (HCV) infection is increasing worldwide. Cytotoxic Tlymphocyte-associated protein 4 (CTLA-4) may play a role in the intensity of the disease. The aim of this study was to evaluate the association between genetic variants of the CTLA-4 and HCV infection. METHODS: Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was performed as the genotyping assay at four different positions (+49 A>G, -318 C>T, -1722 T>C, and - 1661 A>G). Haplotypes were analyzed using PHASE software. Sixty-five HCV patients and 65 healthy individuals as controls who were referred to the hepatitis clinic in Mashhad, Iran, were recruited. Genomic DNA was extracted from whole blood of participants. RESULTS: In a dominant analysis model of the -1661 position (GG vs. AA+AG), the AA genotype was more common in controls than in patients (adjusted P = 0.0003; OR = 0.15, 95% CI = 0.051 -0.42). The GCAT haplotype was also more prevalent in controls than in patients (adjusted P = 0.01; OR = 0.40, 95% CI = 0.20-0.81). Furthermore, the ACGT/ACGT diplotype was more common in controls than in patients (P = 0.0037; OR = 0.15, 95% CI = 0.04-0.54). In addition, the ACGT/ACAT diplotype was more frequent in patients than controls (adjusted P =0.003; OR = 2.48, 95% CI = 1.37- 4.50). CONCLUSION: Our results indicated that polymorphisms in CTLA-4 and certain haplotypes may affect the risk of HCV infection in our population, although a larger sample size may be required to confirm this association.

Altered expression of CXCR3 and CCR6 and their ligands in HTLV-1 carriers and HAM/TSP patients.

Recruitment of leukocytes by chemokines and chemokine receptors to CNS plays a crucial role in the induction of inflammatory response in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In the present study, chemokine and chemokine receptors involved in trafficking of lymphocytes to the CNS were measured in HAM/TSP patients, HTLV-1 asymptomatic carriers (ACs), and healthy controls. The PVL, CCR6, and CXCR3 mRNA expression, and CXCL9 and CXCL10 protein levels were measured in all subjects. The PVL of HAM/TSP patients was higher than that of ACs (P = 0.02). CCR6 expression was higher in HAM/TSP patients and in ACs compared to the healthy controls (P = 0.005 and P = 0.04, respectively). A significant difference was observed in CCR6 expression when a combination of HAM/TSP patients and ACs were compared to the healthy individuals (P = 0.005). Furthermore, there was a significantly lower CXCR3 expression between HAM/TSP and control groups (P = 0.001), and between the ACs and healthy controls (P = 0.001). However, the increased CXCR3 expression in ACs compared to HAM/TSP patients was not significant. Furthermore, the CXCL10 protein levels in HAM/TSP patients was higher than in controls (P = 0.012), and CXCL9 protein levels was also higher in the HAM/TSP and ACs groups than in the controls (P = 0.001 and P = 0.004, respectively). In conclusion, it seems that decreased expression of CXCR3 and higher expression of CCR6 were associated with HTLV-1 infection, what indicate that these alterations may favor virus dissemination but not disease manifestation.

Haplotype Analysis of Hemochromatosis Gene Polymorphisms in Chronic Hepatitis C Virus Infection: A Case Control Study.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is frequently associated with elevated serum iron markers. Polymorphisms in the hemochromatosis (HFE) genes are responsible for iron accumulation in most cases of hemochromatosis, and may play a role in HCV infection. OBJECTIVES: We aimed to assess the prevalence of HFE gene polymorphisms in a group of Iranian HCV-infected patients, and to explore the association of these polymorphisms with HCV infection. PATIENTS AND METHODS: HFE gene polymorphisms were examined in a total of 69 HCV patients and 69 healthy controls using polymerase chain reaction and restriction fragment length polymorphism techniques. Haplotype and diplotype analyses were performed using PHASE software. RESULTS: In a recessive analysis model of the His63Asp (H63D) locus (HH vs. HD + DD), the HH genotype was more common in patients compared to controls (adjusted P = 0.012; OR = 6.42 [95% CI: 1.51 - 27.33]). Also, in a recessive analysis model of the Cys282Tyr (C282Y) locus (CC vs. CY + YY), the CC genotype was more frequent in patients compared to controls (adjusted P = 0.03; OR = 5.06 [95% CI: 1.13 - 22.06]). In addition, there was a significant association between the HC haplotype and the HCDC diplotype and HCV infection. CONCLUSIONS: Polymorphism in the hemochromatosis gene may confer some degree of risk for HCV infection, and individuals carrying the H and C alleles may be susceptible to this disease; however, a larger sample of HCV patients and healthy individuals may be necessary to further illustrate the role of these polymorphisms in HCV.

Prevalence and phylogenetic analysis of HTLV-1 in a segregated population in Iran.

Human T-lymphotropic virus type 1 (HTLV-1) infection is an important health issue that affects a variety of endemic areas. The Khorasan province, mainly its capital Mashhad in northeastern Iran, was reported to be as one of these endemic regions. Torbat-e Heydarieh, a large city Southwest border to Mashhad with a segregated population was investigated for the prevalence and associated risk factors of HTLV-1 infection in 400 randomly selected individuals. Blood samples were tested for the presence of HTLV-1 antibodies via the ELISA method and then were confirmed by an Immunoblot test. For the presence of HTLV-1 in lymphocytes of infected subjects, PCR was performed on LTR and TAX regions. DNA sequencing of LTR fragment was also carried out to determine the phylogenetic of HTLV-1, using the Maximum likelihood method. HTLV-1 sero-reactivity (sero-prevalence) among the study population was 2% (8/400), of which 1.25% had HTLV-1 provirus in lymphocytes (actual prevalence). HTLV-1 infection was significantly associated with the age, marital status, and history of blood transfusion (P < 0.05). However, there were no statistical differences between HTLV-1 infection, and gender, surgery, and hospitalization. In regression analysis, age showed the most significant correlation with the infection (P = 0.006, OR = 4.33). Based on our phylogenetic study, the HTLV-1 prevalent sequence type of Torbat-e Heydarieh belongs to the cosmopolitan subtype A. HTLV-1 prevalence in Torbat-e Heydarieh (1.25%) is low comparing to those of both Mashhad (2-3%) and Neishabour (3.5-5%) in the province of Khorasan. Thus, traveling mobility and population mixing such as marriage, bureaucratic affairs, occupation, and economic activities could be the usual routs of HTLV-1 new wave of spreading in this segregated city.

The association between oral lichen planus and hepatitis C virus infection; a report from northeast of iran.

BACKGROUND: The association between hepatitis C virus (HCV) infection and oral lichen planus (OLP) has been the focus of many studies. Fifteen percent of HCV infections lead to sets of extrahepatic manifestations including lichen planus (LP). The prevalence of HCV is heavily influenced by geographical location. OBJECTIVES: This study aimed to evaluate the relationship between OLP and HCV infection in Mashhad, northeast of Iran. MATERIALS AND METHODS: Blood samples were taken from 134 OLP patients and 134 healthy controls (without OLP) to screen for anti-HCV by ELISA (third generation) and reverse transcription polymerase chain reaction (RT-PCR) for HCV-RNA. RESULTS: Of the 134 OLP patients only three (2.23 %) had HCV infection where both anti-HCV and HCV-RNA were positive. All controls were negative for both anti-HCV and HCV-RNA (P = 0.082). CONCLUSIONS: Our investigation illustrated that the prevalence of hepatitis C was higher among OLP patients compared to the control group. These findings are in line with previous results that reported a hepatitis C prevalence of 0.19% among the general population of Mashhad.

Haplotype analysis of interleukin-10 gene promoter polymorphisms in chronic hepatitis C infection: a case control study.

High prevalence of hepatitis c virus (HCV) infection in some areas necessitates more investigations of the causative factors. Genetic factors that cause disruption in operation or secretion of interleukin 10 (IL-10), an anti-inflammatory cytokine, may play a role in the intensity of the disease. The aim of this study was to evaluate genetic variants of IL-10 gene polymorphisms in HCV patients and their relationship with HCV disease. Fifty HCV patients and the same number of healthy individuals who were referred to hepatitis clinic in Mashhad, northeast of Iran, were recruited. Genomic DNA was extracted from whole blood. Genotyping for IL-10 gene promoter polymorphisms in three positions (-1082 G>A, -819 C>T and -592 C>A) was conducted by amplification refractory mutation system-polymerase chain reaction. Haplotype analysis was performed using PHASE software. In a recessive analysis model of the -1082 position (GG vs. AA+AG), GG genotype was more common in patients (adjusted p = 0.02; OR = 4.66 [95% CI 1.31-16.35]). Also, ATA haplotype was more prevalent in HCV patients (adjusted p = 0.061; OR = 1.87 [95% CI 0.97-3.61]). Also, ATC/GCA diplotypes were more common in controls (adjusted p=0.002; adjusted OR = 0.27 [95% CI 0.11-0.63]). Although we found a possible association between IL-10 promoter polymorphisms and HCV infection, certain genotypes or diplotypes may confer a higher risk or susceptibility for developing HCV infection.

Genotype distribution of hepatitis C virus in Khorasan Razavi Province, Iran.

BACKGROUND/AIM: Several types of the hepatitis C virus (HCV), with variations in different parts of the genome, have been isolated from different regions of the world. Based on heterogenic sequences in the isolated genome, HCV is classified into different genotypes and subtypes. Data on distribution of HCV genotypes in a certain region could be important to patient management. Therefore, this study was conducted to determine the distribution of HCV in Mashhad, Northeast Iran. MATERIALS AND METHODS: This cross-sectional study was conducted on 103 patients with HCV infections in Mashhad. Among the participants, at least 22 (21.4%) were intravenous drug users. HCV seropositivity was determined by an enzyme-linked immunosorbent assay and was confirmed by reverse transcriptase polymerase chain reaction. HCV-positive samples were selected for HCV genotyping using genotype specific primers. RESULTS: Of 103 subjects, 43 (41.7%) and 34 (33.0%) had genotypes 1a and 3a, respectively. Other genotypes including 1b, 2a, 2b, 3b, and 5a were found in 4 (3.9%), 1 (1.0%), 3 (2.9%), 4 (3.9%), and 1 (1.0%), respectively. Coinfections with 2 genotypes were also observed in 11 (10.7%) patients. Genotyping for 2 (1.9%) of 103 samples did not produce any results. CONCLUSION: Genotypes la and 3a were found to be the most prevalent HCV genotypes in Mashhad, Iran.

The prevalence of hepatitis C virus in mashhad, iran: a population-based study.

BACKGROUND: Hepatitis C virus (HCV) infection is a significant health problem throughout the world. Chronic form of the disease is found in about 75% to 85% of the newly infected individuals. The chronic infection may lead to severe forms including chronic liver disease, cirrhosis and with a higher mortality rate, hepatocellular carcinoma. Since no vaccine has yet been developed against HCV, there is an increasing need to take measures to control the spread of the infection. Therefore, epidemiologic study of the virus is important to manage and monitor the spread of the virus in the community. OBJECTIVES: The aim of this study was to determine the prevalence of hepatitis C seropositivity in the general population of Mashhad, northeast of Iran. PATIENTS AND METHODS: Three thousand, eight hundred and seventy (3870) individuals living in the city of Mashhad were recruited using cluster sampling method. HCV seropositivity was determined with HCV antibody detection ELISA kit and was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) method. RESULTS: In this study the overall seroprevalence of hepatitis C was founded to be 0.2% by using ELISA method. However, the overall Hepatitis C virus infection prevalence was found to be 0.13% with RT-PCR method. CONCLUSIONS: Our study suggested that the prevalence rate of Hepatitis C virus is below 1% in the general population of Mashhad.