Pesticide residues in drinking water treatment plants and human health risk assessment: a case study from Northern Iran.

These days, the presence of pesticide residues in drinking water sources is a serious concern. In drinking water treatment plants (DWTPs), various methods have been proposed to remove pesticide residues. This study was designed with the objectives of monitoring the occurrence and seasonal variations of pesticides in the output of drinking water treatment plants in two Northern provinces of Iran, Gilan and Golestan, and identifying their human health risks. Seventeen pesticide residues from different chemical structures were determined by using a gas chromatograph-mass spectrometer (GC-MS). The results showed that only Alachlor, Diazinon, Fenitrothion, Malathion, and Chlorpyrifos were detected. The pesticide concentrations ranged from ND to 405.3 ng/L and were higher in the first half-year period. The total non-carcinogenic human health risks was in safe range for infants, children, and adults (HI < 1). The carcinogenic human health risks of Alachlor for infants, children, and adults were in the range of 4.3 × 10-7 to 1.3 × 10-6, 2.0 × 10-7 to 9.6 × 10-7, and 1.1 × 10-7 to 5.5 × 10-7, respectively. These values do not pose health risks for adults and children, but may present a possible cancer risk for infants in two DWTPs of Golestan. In conclusion, considering the possibility of exposure to these pesticides through other routes, simultaneously, it is suggested to carry out a study that examines the level of risk by considering all exposure routes. We also propose stricter regulations for the sale and use of pesticides in Iran.

Erythrocytes polyunsaturated fatty acids mediate relationship between dietary patterns and depression.

Background: This study aimed to examine the association between depression and dietary patterns via the intermediary role of erythrocytes polyunsaturated fatty acids (PUFA). Methods: In this individually matched case-control study, the dietary patterns were extracted for 330 individuals using factor analysis. Furthermore, erythrocyte PUFAs including n-3 and n-6 were assessed using a GC-Mass spectrometry analytical method for 84 people. Depression was diagnosed using the criteria mentioned in the Diagnostic and Statistical Manual of Mental Disorders. The dietary patterns were also extracted using a valid and reliable semi-quantitative food frequency questionnaire. Results: The findings showed that healthy dietary patterns were related to the risk of depression (P = 0.01, odds ratio (OR) = 0.31, 95% confidence interval (CI): 0.14-0.68) by the increase of ratio n-3 /n-6 PUFA (p ≤ 0.03) and decrease of ratio n-6 /n-3 PUFA (p ≤ 0.005). Moreover, the unhealthy dietary patterns were associated with the risk of depression (P = 0.02, OR = 2.7, 95%CI: 1.25-5.9) by the decrease of ratio n-3/n-6 PUFA (p ≤ 0.03) and increase of ratio n-6/n-3 PUFA (p ≤ 0.001). Conclusion: Based on the results, the type of dietary pattern is related to the risk of depression considering the changes in n-3 and n-6 PUFA as well as the ratio of n-3 to n-6 as the mediator variables. Of course, further studies are required in this area.

Development and validation of a high-performance liquid chromatography method for determination of lisinopril in human plasma by magnetic solid-phase extraction and pre-column derivatization.

A sensitive, reliable and simple HPLC method was developed for the determination of lisinopril in human plasma. The method consists of extraction and clean-up steps based on magnetic solid-phase extraction and pre-column derivatization with a fluorescent reagent. The mobile phase consisted of a mixture of methanol-sodium dihydrogen phosphate (pH 3.0; 0.005 m; 75:25, v/v). The flow rate was set at 0.7 mL/min. Fluorescence detection was performed at 470nm excitation and 530nm emission wavelengths. Total chromatography run time was 5 min. The average extraction recovery of lisinopril and fluvoxamine (internal standard) was ≥82.8%. The limits of detection and quantification were determined as 1 and 3 ng/mL respectively. The method exhibited a linear calibration line over the concentration range of 3-1000 ng/mL with coefficient of determination (r2 ) of ≥0.98. The within-run and between-run precisions were satisfactory with values of CV of 1.8-12.8% (accuracy from 99.2 to 94.7%) and 2.4-13.7% (accuracy from 99.5 to 92.2%), respectively. These developments led to considerable improvement in method sensitivity and reliability. The method was validated according to the US Food and Drug Administration guidelines. Therefore, it can be considered as a suitable method for determination of lisinopril in plasma samples.

The Effect of Storage Time, Temperature and Type of Packaging on the Release of Phthalate Esters into PackedAcidic Liquids.

Acidic liquids such as verjuice, lemon juice and vinegar are frequently consumed in Iran. Different kinds of acidic liquids are packaged in polyethylene terephthalate (PET) and high-density polyethylene (HDPE) bottles. There is evidence indicating that phthalates can leach from PET and HDPE bottles into their contents. In this work the effect of storage time, temperature and bottle type on the migration of phthalates from packaging materials into acidic liquids is studied by analyzing the samples stored under different conditions, before storage and after 2, 4 and 6 months of storage. The determined mean phthalate concentrations in µg/L were: <0.04 to 0.501 in verjuice, <0.04 to 0.231 in lemon juice and <0.04 to 0.586 in vinegar. The highest concentrations of diethyl phthalate (DEP) and diethyl hexyl phthalate (DEHP) were found in PET and HDPE bottles, respectively. Results of analyses before and after storage indicate that under some storage conditions, the concentrations of DEP, DEHP and dibutyl phthalate (DBP) increased in acidic liquids. The possible migration of phthalic acid esters from plastic packaging materials into the contents was indicated by the results of the present study.

Endocrine disruptor phthalates in bottled water: daily exposure and health risk assessment in pregnant and lactating women.

Over the last decade, the consumption of water bottled in polyethylene terephthalate (PET) has considerably increased, raising concerns over water quality and packaged materials. This study aims to investigate the levels of the anti-androgenic phthalates including bis-(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and benzyl butyl phthalate (BBP), in bottled water and its corresponding health risks in pregnant and lactating women. The phthalate levels were measured in six different brands of bottled water exposed to temperatures ranging between -18 and 40 °C and sunlight for 45 days. The phthalate was quantified using the gas chromatography-mass spectrometry (GC-MS). In addition, the non-carcinogenic effects were assessed using hazard quotient (HQ) approach, and cumulative health risk assessment was performed on the basis of hazard index (HI) calculation. In order to assess the carcinogenic risk due to the possible carcinogen DEHP (group 2B), the excess lifetime cancer risk (ELCR) was used. DEHP and DBP contaminants were detected at different storage conditions in all of the bottled water samples during the storage time. BBP was only detected at high temperature (≥25 °C) and outdoor conditions. The maximum concentrations of all phthalates were observed when water samples were kept at 40 °C. In contrast, storage at freezing conditions had no significant effect on the concentration level of all phthalates. The estimated intake by women was between 0.0021 µg/kg/day for BBP and 0.07 µg/kg/day for DEHP. The highest HQ for phthalate intake via bottled water consumption was much lower than 1 (HQ < 0.004), which implies that adverse effects are very unlikely to occur. The execution of a cumulative risk assessment for combined phthalate exposure demonstrated that the HIs for anti-androgenic effect were lower than 1 in all of the conditions. Furthermore, ELCR for DEHP based on the highest detected level was found to be less than 10(-6), which is considered acceptable. Our results prove that the levels of phthalates in bottled water are not a health concern for pregnant and lactating women. Consequently, PET-bottled water is not a major contributor to phthalate intake for most individuals.

Determination and source identification of polycyclic aromatics hydrocarbons in Karaj River, Iran.

Sixteen priority polycyclic aromatic hydrocarbons (PAHs) were measured in six stations in Karaj River, which is the main resource of drinking water in Tehran. The single PAHs concentrations ranged from not detected to 2,327.8 ng L(-1), with a mean value of 31.5 ng L(-1). The total PAHs concentrations ranged from 25.6, in the spring, to 4,040.3 ng L(-1), in the summer. PAHs concentrations in different sampling stations were similar (p = 0.33-0.99), but strong relationships were detected between seasonal variations and total PAHs, BaP equivalent and carcinogen PAHs concentration (p = 0.010-0.037). Results showed that carcinogen PAHs comprised 7 %-92 % of detected PAHs in different sampling stations. The concentration of benzo(a)pyrene, as an indicator, was lower than the permissible limit of the World Health Organization; however, in some samples, carcinogen PAHs concentrations were higher than the permissible limits of the European Union and USA Environmental Protection Agency regulations for drinking water.

Effect of frozen storage on the anthocyanins and phenolic components of pomegranate juice.

Pomegranate juice's valuable nutritional components may be reduced during its processing or storage. This work examined the effect of frozen storage at -25 °C on some chemical characteristics of pomegranate juice. Total anthocyanin content of pomegranate juice, which was measured using the pH differential method, decreased by 11% after 20 days of frozen storage. Phenolic components, measured using a Folin and Ciocalteu assay by means of a UV-vis spectrophotometer, decreased by 29% after 20 days of frozen storage. Antioxidant activity, measured based on the radical scavenging properties of the juice using the 2,2-diphenyl-1-picrylhydrazyl method, decreased by 50% after 20 days of frozen storage. Pomegranate juice has 5 major anthocyanins, including Cyanidin 3-glucoside, Cyanidin 3,5-diglucoside, Delphinidin 3-glucoside, Pelargonidin 3-glucoside and Pelargonidin 3,5-diglucoside are 5 major anthocyanins of pomegranate juice. They were measured using the LC-MS method and results showed that Pelargonidin 3,5- diglucoside had the greatest decrease. Also, the LC-MS method showed that ellagic acid decreased by 15%.

Dispersive micro-solid phase extraction based on two MOFs as highly effective adsorbents for analysis of nilotinib in plasma and wastewater.

BACKGROUND: Nilotinib (NIL) is a prescription medication employed in the treatment of specific types of leukemia, namely chronic myelogenous leukemia (CML). The determination of NIL levels in patients undergoing treatment for CML is of paramount importance for effective management of treatment and toxicity. Also, monitoring and controlling its level in wastewater sources could help scientists to identify potential hotspots of contamination and take appropriate measures to mitigate their impact on the environment and public health. OBJECTIVES: This study presents a D-µ-SPE technique utilizing two MOFs as adsorbents for the efficient detection of nilotinib in plasma and wastewater samples for the first time. METHODS: Two highly effective MOFs, MIL-101(Fe) and MIL-53(Al), were synthesized and applied as dispersive micro-solid phase extraction (D-µ-SPE) adsorbents for the extraction of nilotinib coupled with HPLC-UV in a short time of analysis. Experimental parameters affecting extraction efficacy such as adsorbent amount, ionic strength, pH value, adsorption-desorption time and type of elution solvent, were optimized. RESULTS: Under optimal experimental conditions, the linear dynamic was achieved in the range of 0.25-5.00 µg/mL in human plasma and 0.01-0.20 µg/mL in wastewater. The extraction recovery was in the range of 89.18-91.53% and 94.39-99.60% for nilotinib and MIL-101(Fe) and also 91.22-97.35% and 98.14-100.78% for nilotinib and MIL-53(Al) from human plasma and wastewater respectively. CONCLUSION: HPLC-UV determination of nilotinib after the D-µ-SPE method showed acceptable accuracy and precision in both plasma and wastewater. In comparison between the two adsorbents, the extraction procedure was easier and faster with MIL-53(Al) as the adsorbent.

A Phase 1 Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of (2R,6R)-Hydroxynorketamine in Healthy Volunteers.

(R,S)-Ketamine (ketamine) is a dissociative anesthetic that also possesses analgesic and antidepressant activity. Undesirable dissociative side effects and misuse potential limit expanded use of ketamine in several mental health disorders despite promising clinical activity and intensifying medical need. (2R,6R)-Hydroxynorketamine (RR-HNK) is a metabolite of ketamine that lacks anesthetic and dissociative activity but maintains antidepressant and analgesic activity in multiple preclinical models. To enable future assessments in selected human indications, we report the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of RR-HNK in a Phase 1 study in healthy volunteers (NCT04711005). A six-level single-ascending dose (SAD) (0.1-4 mg/kg) and a two-level multiple ascending dose (MAD) (1 and 2 mg/kg) study was performed using a 40-minute IV administration emulating the common practice for ketamine administration for depression. Safety assessments showed RR-HNK possessed a minimal adverse event profile and no serious adverse events at all doses examined. Evaluations of dissociation and sedation demonstrated that RR-HNK did not possess anesthetic or dissociative characteristics in the doses examined. RR-HNK PK parameters were measured in both the SAD and MAD studies and exhibited dose-proportional increases in exposure. Quantitative electroencephalography (EEG) measurements collected as a PD parameter based on preclinical findings and ketamine's established effect on gamma-power oscillations demonstrated increases of gamma power in some participants at the lower/mid-range doses examined. Cerebrospinal fluid examination confirmed RR-HNK exposure within the central nervous system (CNS). Collectively, these data demonstrate RR-HNK is well tolerated with an acceptable PK profile and promising PD outcomes to support the progression into Phase 2.

The therapeutic effect of larval saliva and hemolymph of Lucilia sericata on the treatment of Leishmania major lesion in BALB/c mice946.

BACKGROUND: Treatment of cutaneous leishmaniasis (CL) remains a major challenge for the public health and medical community. It has been claimed that natural compounds derived from fly larvae have anti-leishmania properties against some species of Leishmania. The present study aimed at assessing the in vitro effects of larval products of Lucilia sericata against the promastigote and intracellular amastigote forms of Leishmania major. Also, the therapeutic effect of larval products on lesions induced by L. major infection was evaluated in BALB/c mice models. METHODS: Parasite specimens and macrophage cells were exposed to varying concentrations of larval products for 24-120 h. Lesion progression and parasite load were investigated in the models to assess the therapeutic effects of the products. RESULTS: The larval products displayed more potent cytotoxicity against L. major promastigotes. The IC50 values for larval saliva and hemolymph were 100.6 and 37.96 ug/ml, respectively. The IC50 of glucantime was 9.480 ug/ml. Also, the saliva and hemolymph of L. sericata exhibited higher cytotoxicity against the promastigotes of L. major but were less toxic to the macrophage cells. Treatment with leishmanicidal agents derived from larvae of L. sericata decreased the infection rate and the number of amastigotes per infected host cell at all concentrations. Lesion size was significantly (F (7, 38) = 8.54, P < 0.0001) smaller in the treated mice compared with the untreated control group. The average parasite burden in the treated mice groups (1.81 ± 0.74, 1.03 ± 0.45 and 3.37 ± 0.41) was similar to the group treated with a daily injection of glucantime (1.77 ± 0.99) and significantly lower (F (7, 16) = 66.39, P < 0.0001) than in the untreated control group (6.72 ± 2.37). CONCLUSIONS: The results suggest that the larval products of L. sericata were effective against L. major parasites both in vivo and in vitro. However, more clinical trial studies are recommended to evaluate the effects of these larval products on human subjects.

Simultaneous determination of parathion, malathion, diazinon, and pirimiphos methyl in dried medicinal plants using solid-phase microextraction fibre coated with single-walled carbon nanotubes.

A reliable and sensitive headspace solid-phase microextraction gas chromatography-mass spectrometry method for simultaneous determination of different organophosphorus pesticides in dried medicinal plant samples is described. The analytes were extracted by single-walled carbon nanotubes as a new solid-phase microextraction adsorbent. The developed method showed good performance. For diazinon and pirimiphos methyl calibration, curves were linear (r(2) ≥ 0.993) over the concentration ranges from 1.5 to 300 ng g(-1), and the limit of detection at signal-to-noise ratio of 3 was 0.3 ng g(-1). For parathion and malathion, the linear range and limit of detection were 2.5-300 (r(2) ≥ 0.991) and 0.5 ng g(-1), respectively. In addition, a comparative study between the single-walled carbon nanotubes and a commercial polydimethylsiloxane fibre for the determination of target analytes was carried out. Single-walled carbon nanotubes fibre showed higher extraction capacity, better thermal stability (over 350 °C), and longer lifespan (over 250 times) than the commercial polydimethylsiloxane fibre. The developed method was successfully applied to determine target organophosphorus pesticides in real samples.

Butyltin compounds in fish commonly sold in north of Iran.

Levels of tributyltin (TBT) and its degradation products, mono (MBT) and dibutyltin (DBT), were monitored in fish commonly consumed in Iran. Samples were purchased from fish markets at seasonal intervals in 2010 along the North coast of Iran. Concentration of MBT, DBT and TBT in the muscle of these fish were in the range of n.d. -1.01 ± 0.84, n.d. -0.33 ± 0.26 and n.d. -4.31 ± 0.95 ngg(-1) (wet weight), respectively. Residue levels of butyltins were found lower than the tolerable average residue level of 100 ngg(-1) (wet weight).

Levels of organophosphorus pesticides in medicinal plants commonly consumed in Iran.

The frequent occurrence of pesticide residues in herbal materials was indicated by previous studies. In this study, the concentration of some of the organophosphorus pesticides including parathion, malathion, diazinon and pirimiphos methyl in different kinds of medicinal plants were determined. The samples were collected randomly from ten local markets of different areas of Iran. At the detection limit of 0.5 ng g-1, parathion and pirimiphos methyl were not detected in any of the samples. Some amounts of malathion and diazinon were found in Zataria, Matricaria chamomile, Spearmint and Cumin Seed samples while, the concentrations of target organophosphorus pesticides in Borage samples were below the detection limits of the methods which could be a result of intensive transformation of organophosphorus pesticides by Borage. In addition the organophosphorus pesticides were detected in all of the samples below the maximum residue levels (MRLs) proposed by the international organizations.

Exposure assessment to trichloroethylene and perchloroethylene for workers in the dry cleaning industry.

Perchloroethylene and trichloroethylene are two particular organochloro compounds, are often used for dry-cleaning. In the present study the excretion of urinary Perchloroethylene and trichloroethylene were evaluated as biomarkers of exposure to these compounds. The mean value of Perchloroethylene in breathing zone and the total Perchloroethylene uptake during the work shift of the three groups of dry-cleaning workers according to the capacity of the dry-cleaning machine (8, 12 and 18 kg) were 31.04, 50.87 and 120.99 mg m(-3) and 11.46, 22.6 and 41.6 µg L(-1), respectively, which were significantly greater than the occupationally nonexposed groups. A good correlation (r = 0.907) between the mean values of Perchloroethylene in breathing zone and the urinary concentrations was observed.

Impact of smoking on oxidant/antioxidant status and oxidative stress index levels in serum of the university students.

BACKGROUND: Despite frequent warnings of irreversible side effects of smoking in public media, the consumption of cigarette is increasing dramatically in both developed and developing countries. Cigarette smoke contains different kinds of chemicals, which all capable of inducing free radical production. There are studies supporting the idea that these free radicals have adverse effects in body and causing oxidative stress. Total antioxidant capacity (TAC) is considered as the total effect of all antioxidants and total oxidant status (TOS) shows the total effect of all oxidants existing in body fluids. Therefore, this research focused on the measurement and comparison of these markers in the serum of university students. METHODS: This study designed to determine the total antioxidant capacity, total oxidant status and oxidative stress index levels in the serum of active smokers, passive smokers and non-smokers in university students. A total of 150 participants were included in the study. The study population consisted of 50 smokers, 50 passive smokers and 50 nonsmokers. In serum samples, the levels of TAC and TOS were measured by spectrophotometric method using Rel Assay Diagnostics kit. Oxidative stress index was calculated through the TOS/TAC formula in three groups. RESULTS: The mean value TAC levels in serum samples of the three groups of smokers, passive smokers and nonsmokers were 1.096, 1.220 and 1.844 mmol Trolox equivalent/L, respectively, which were significantly greater in nonsmokers than smokers and passive smokers. The mean value TOS levels in serum samples of the three groups of smokers, passive smokers and nonsmokers were 13.747, 11.099 and 7.6510 µmol H2O2 equivalent/L, respectively, which were significantly lower in nonsmokers than two other groups. OSI values in smokers and passive smokers were significantly higher than the control group. CONCLUSIONS: According to our findings, the antioxidant capacity in all smokers (active and inactive) was less than the control group (non-smokers). The results of this study showed that smoking reduces the activity of the antioxidant defense system and activates the oxidative stress system in the body. Based on these findings, it can be clearly concluded that the decrease in antioxidant capacity in smokers is associated with increased production of oxidants and free radicals.

Hemoglobin adducts as an important marker of chronic exposure to low concentration of 1, 3-butadiene.

BACKGROUND: 1, 3-Butadiene is a famous industrial compound which occurs in gasoline and diesel exhaust and in cigarette smoke. Based on little evidence of carcinogenicity in laboratory animals and humans, it was classified as a probable carcinogen. The potential of exposure to gasoline and diesel exhaust containing these chemical compounds is very considerable in urban areas. According to studies, in estimation of workers' chronic exposure with biological samples, analysis of the concentration of related hemoglobin adducts seems to give the most valid estimation of exposure. METHODS: This study designed to determine the level of chronic exposure in gas station workers and traffic policemen during routine work shift, by an appropriate biological marker. In this regards, 25 gas station workers, 25 policemen engaged in traffic control, and 25 occupationally non-exposed persons were studied. Blood samples were obtained after the work shift from each person. The level of selected hemoglobin adduct, 1- and 2-hydroxy-3-butenyl valine (MHBVal) was determined by using GC-MS after a modified Edman degradation and a further acetylation. RESULTS: There were significant differences among the mean concentrations of MHBVal in blood samples of gas station workers, policemen and occupationally non-exposed persons. The mean airborne levels of 1, 3-Butadiene over 60 days, differed significantly among different studied groups (ANOVA: p < 0.05 and Kruskal-Wallis test: p < 0.05). CONCLUSION: There was a significant difference in MHBVal concentrations between job categories (p < 0.05 by ANOVA and Kruskal-Wallis test), and gas station workers and policemen were found to be probably the most exposed groups in this research.

Synthesis and characterization of tetraethylene pentamine functionalized MIL-101(Cr) for removal of metals from water.

PURPOSE: Metal contamination in water is a worldwide persistent problem. We developed a nano-adsorbent, TEPA-MIL-101(Cr) that exhibits effective removal of heavy metals from real water samples. METHODS: MIL-101(Cr) was synthesized under solvo-thermal condition. Then MIL-101(Cr) was dehydrated and degassed at high temperature under vacuum to generate the coordinately unsaturated sites which are used for tetraethylene pentamine (TEPA) grafting. The structures, morphologies, and compositions of the sorbents have been characterized. Langmuir and Freundlich isotherm models were applied for describing the adsorption process onto TEPA-MIL-101(Cr). RESULTS: The successful grafting of TEPA on MIL-101(Cr) was verified by Fourier transform infrared. The results of X-ray diffraction, scanning electron microscopy, and CHN analysis show that the structure of TEPA-MIL-101(Cr) retains the original structure of MIL-101(Cr). Thermogravimetric analysis indicates thermo-stability of the adsorbent up to 300 °C. Optimal conditions for adsorption were determined as pH = 6.5 and contact time = 1 h. The adsorption capacities of TEPA-MIL-101(Cr) for Pb(II), Cu(II), Cd(II), and Co(II) from aqueous samples were 227.5, 217.7, 221.4, and 215.6 mg/g respectively, which is on average more than 8 times that of MIL-101(Cr). Analysis of Langmuir and Freundlich models for describing the adsorption isotherms of TEPA-MIL-101(Cr) reveals that the metal ions were absorbed onto TEPA-MIL-101(Cr) by a favorable physical absorption process. CONCLUSIONS: TEPA-MIL-101(Cr) was synthesized successfully by a simple, and cost-effective method. The removal efficiency of TEPA-MIL-101(Cr) for the metal ions achieved more than 95 % in real water samples, which in addition to its thermal stability character make it a promising candidate for water treatment purposes.

The leishmanicidal effect of Lucilia sericata larval saliva and hemolymph on in vitro Leishmania tropica.

BACKGROUND: Leishmaniasis is a major parasitic disease worldwide, except in Australia and Antarctica, and it poses a significant public health problem. Due to the absence of safe and effective vaccines and drugs, researchers have begun an extensive search for new drugs. The aim of the current study was to investigate the in vitro leishmanicidal activity of larval saliva and hemolymph of Lucilia sericata on Leishmania tropica. METHODS: The effects of different concentrations of larval products on promastigotes and intracellular amastigotes of L. tropica were investigated using the mouse cell line J774A.1 and peritoneal macrophages as host cells. The 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and direct observation and counting method were used to assess the inhibitory effects and cell cytotoxicity of the larval products. The effects of larval products on the amastigote form of L. tropica were quantitatively estimated by calculating the rate of macrophage infection, number of amastigotes per infected macrophage cell, parasite load and survival index. RESULTS: The 50% cytotoxicity concentration (CC50) value of both larval saliva and hemolymph was 750 µg/ml, and the 50% inhibitory concentration (IC50) values were 134 µg/ml and 60 µg/ml for larval saliva and larval hemolymph, respectively. The IC50 for Glucantime, used a positive control, was (11.65 µg/ml). Statistically significant differences in viability percentages of promastigotes were observed for different doses of both larval saliva and hemolymph when compared with the negative control (p ≤ 0.0001). Microscopic evaluation of the amastigote forms revealed that treatment with 150 µg/ml larval hemolymph and 450 µg/ml larval saliva significantly decreased the rate of macrophage infection and the number of amastigotes per infected macrophage cell. CONCLUSION: Larval saliva and hemolymph of L. sericata have acceptable leishmanicidal properties against L. tropica.

Evaluation of Susceptibility Status of Phlebotomus papatasi, the Main Vector of Zoonotic Cutaneous Leishmaniasis, to Different WHO Recommended Insecticides in an Endemic Focus, Central Iran.

Background: Among neglected zoonotic diseases, leishmaniases caused by Leishmania parasite through infected female sand fly bite, are a group of diseases found in 98 countries and territories representing a critical burden of disease worldwide. Vector management plays a crucial role in reducing the burden of vector-borne diseases by WHO's global plan. The objective of the current study was to assess the susceptibility status of wild phlebotomine sand flies from Esfahan Province, central Iran, to the recommended insecticides by WHO. Methods: Sand flies were collected by mouth aspirator in Matin Abad desert Eco-resort and were tested using WHO adult mosquito test kit against Dichlorodiphenyltrichloroethane (DDT) 4%, Deltamethrin 0.05%, Malathion 5% and Propoxur 0.1%. The number of knockdown sand flies were recorded during exposure time in ten minutes interval for DDT and Deltamethrin and they were allowed to recover for 24 hours. Knockdown Time50 (KD50) and KD90 were generated for them using Probit software. They were mounted and identified by valid keys. Results: Among the tested insecticides against female Phlebotomus papatasi, DDT, Deltamethrin, and Malathion recorded the highest mortality rate of 100%, followed by Propoxur with 92.2% mortality for a one-hour exposure. For DDT, KD50 and KD90 were calculated 21.87 and 42.93 and for Deltamethrin, they were 23.74 and 56.50 minutes respectively. Total sand flies exposed with DDT and Deltamethrin shed their leg(s). Conclusion: It is concluded that Ph. papatasi from central Iran is susceptible to DDT, Deltamethrin, Malathion, and Propoxur.

Influence of CYP2C9 polymorphism on metabolism of valproate and its hepatotoxin metabolite in Iranian patients.

Sodium valproate (VPA) has 16 known metabolites in humans. The 2-ene-VPA has anti-convulsant efficacy and 4-ene-VPA is reported to contribute in VPA hepatotoxicity. The formation of 4-ene-VPA is catalyzed by cytochrome P450 2C9 (CYP2C9). CYP2C9 allele mutation is closely related to the attenuation of the enzymatic activity and 4-ene-VPA production. In the present work, VPA, 2-ene-VPA, and 4-ene-VPA in serum of patients receiving VPA were determined and the correlation between CYP2C9 polymorphism and 4-ene-VPA concentration was examined. Blood samplings in 68 patients were performed at two time-points (peak and trough) and one sample blood obtained from 50 healthy volunteers for genotype evaluation. Patients were divided into three groups (22 cases of monotherapy, 19 cases of enzyme inducer therapy, and 27 cases of polytherapy). There was a significant reduction in concentration of VPA and 4-ene-VPA between peak and trough time. In peak concentration, there was a significant correlation between 2-ene-VPA and VPA in all groups. The concentration of 4-ene-VPA in the enzyme inducer and polytherapy group was significantly higher than that of the monotherapy group. The allele frequencies of CYP2C9*1, CYP2C9*2, and CYP2C9*3 were 88.97%, 8.09%, and 2.94% in the patient group and 91%, 6%, and 3% in the normal group, respectively. There was no significant difference in allele frequency in two groups. Mutated alleles didn't have any significant effect on 4-ene-VPA production. No patient showed toxic level of 4-ene-VPA or saturation of ß-oxidation pathway. In conclusion, the role of CYP2C9*2 and CYP2C9*3 in attenuation of 4-ene-VPA formation cannot be confirmed.