Toxicity and Hepatoprotective Effects of ZnO Nanoparticles on Normal and High-Fat Diet-Fed Rat Livers: Mechanism of Action.

This experiment aimed to evaluate the beneficial and toxic properties of synthetic zinc oxide nanoparticles (ZnO NPs) on the liver of normal and high-fat diet (HFD) fed-rats. The ZnO NPs were synthesized and, its characterizations were determined by different techniques. Effect of ZnO NP on cell viability, liver enzymes and lipid accumulation were measured in HepG2 cells after 24 h. After that, rats orally received various dosages of ZnO NPs for period of 4 weeks. Toxicity tests were done to determine the appropriate dose. In the subsequent step, the hepatoprotective effects of 5 mg/kg ZnO NPs were determined in HFD-fed rats (experiment 2). The oxidative stress, NLRP3 inflammasome, inflammatory, and apoptosis pathways were measured. Additionally, the activity of caspase 3, nitric oxide levels, antioxidant capacity, and various biochemical factors were measured. Morphological changes in the rat livers were also evaluated by hematoxylin and eosin (H & E) and Masson trichrome. Liver apoptosis rate was also approved by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Treatment of animals with 5 mg/ZnO NPs revealed potential hepatoprotective properties, while ZnO NPs at the doses of above 10 mg/kg showed toxic effects. Antioxidant enzyme gene expression and activity were significantly augmented, while apoptosis, NLRP3 inflammasome, and inflammation pathways were significantly reduced by 5 mg/kg ZnO NPs. Liver histopathological alterations were restored by 5 mg/kg ZnO NPs in HFD. Our study highlights the hepatoprotective effects of ZnO NPs against the HFD-induced liver damage, involving antioxidant, anti-inflammatory, and anti-apoptotic pathways, indicating their promising therapeutic potential.

Organochlorine knockdown-resistance (kdr) association in housefly (Musca domestica): A systematic review and meta-analysis.

Introduction: Although house flies (Musca domestica) do not directly cause disease in humans, they transmit pathogens to them, which provide the basis for many diseases. The main way to deal with this insect is to use insecticides. Due to the resistance from insecticides, the fight against house flies has been hampered. This study aimed to determine the prevalence of knockdown resistance against organochlorine insecticides in house flies worldwide. Methods: This study was conducted via a systematic review and meta-analysis to investigate the prevalence of knockdown resistance against organochlorine insecticides in house flies. Accordingly, by searching the databases of Web of Science, PubMed, Scopus, Proquest, Bioone, and Embase, all published articles were extracted, and reviewed until the end of May 2022. Statistical data analysis was performed using the random-effects model in the meta-analysis, meta-regression, and I2 index. Results: Nine studies entered the meta-analysis process. Based on this, the prevalence of knockdown resistance against organochlorine insecticide in house flies was estimated to be 49.1%. Meta-regression showed that the prevalence of knockdown resistance increased with increasing years of study but decreased with increasing sample size. Conclusion: According to the findings, about 50% of house flies have knockdown resistance against organochlorine insecticide. As a result, it is necessary to adopt effective and combined methods to combat this insect to control it and prevent the transmission of diseases caused by it.

Evaluation of resistance of human head lice to pyrethroid insecticides: A meta-analysis study.

Introduction: Pediculosis is one of the most common annoying infections caused by parasitic lice in humans. Pyrethroids are one of the main insecticides used to treat this infection. But recently, due to the Resistance of lice to this group of insecticides, its insecticidal effects have been affected. The present study was conducted through a meta-analysis to investigate the prevalence of pyrethroid resistance against these insecticides worldwide. Methods: This study was conducted as a meta-analysis of the prevalence of treatment resistance in human head lice against pyrethroid insecticides worldwide. Based on this, all articles published without a time limit until the end of June 2022 in PubMed/MEDLINE, Web of Science (ISI), Scopus, and Google Scholar databases were extracted and using random-effects meta-analysis model statistical methods in the meta-analysis, Cochrane, Index I2, and funnel plot were analyzed by STATA software. Results: Twenty studies were included in the meta-analysis process. According to this, the prevalence of pyrethroid resistance insecticides in human head lice was estimated at 59% (CI95%: 50%-68%). Among pyrethroid insecticides, the highest prevalence of pyrethroid resistance against permethrin insecticide was 65%. Regarding the prevalence of Resistance by year, the prevalence before 2004 was estimated at 33%, but after 2015, this rate reached 82%. Also, the majority of pyrethroid resistance was estimated at 68% using genetic diagnosis methods and 43% using clinical diagnosis methods. Conclusion: More than half of human head lice pyrethroid resistance insecticides. Based on this, it is recommended that before using this treatment method to treat human head lice Infestation, it should investigate the prevalence of pyrethroid resistance in that area, and if the majority of Resistance is high, alternative or combined treatment methods should be used.

Antidiabetic Effects of Genistein: Mechanism of Action.

Diabetes mellitus is a metabolic disease recognized by abnormal glucose level due to defects in insulin action, insulin secretion, or both. Administration of soybean and isoflavones are accompanied by a lower risk of diabetes. The present review analyzed the previous published papers related to genistein. This isoflavone, which has been used for the prevention of some chronic diseases can inhibit hepatic glucose production, increase ß-cell proliferation, reduce ß-cell apoptosis, and show potential antioxidant and anti-diabetic effects. Therefore, genistein may be useful in the management of diabetes. The beneficial effects of this isoflavone on metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, and cancer have been reported in animal and human studies. Moreover, genistein reduces hepatic glucose production, normalizes hyperglycemia, and gut microbiota and exhibits potential anti-oxidative, anti-apoptotic, and hypolipidemic effects. However, studies on the underlying mechanisms of the action of genistein are very limited. Therefore, the present study reviews multifaceted aspects of genistein to reveal a possible anti-diabetic mechanism of this agent. Genistein by regulating several signaling pathways can be used for the prevention and management of diabetes.

Impact of COVID-19 pandemic on the diagnosis of patients with skin cancer: a systematic review protocol.

INTRODUCTION: The COVID-19 pandemic has changed aspects of patient care in the many scheduled medical activities, restricted access to healthcare facilities, and affected the diagnosis and organisation of patients with other health problems, specifically skin cancer. Skin cancer, the uninhibited progress of atypical skin cells, happens with unrepaired DNA genetic faults that lead them to multiply and create malignant tumours. Currently, dermatologists perform skin cancer diagnosis based on their specialised experience using the results of pathological tests from the skin biopsy. Sometimes, some specialists advise sonography imaging to check the skin tissue as a non-invasive method. The outbreak has led to postponements in the treatment and diagnosis of patients with skin cancer, including diagnostic delays because of limitations of diagnostic capacities and delays in referring patients to the physician. The purpose of this review is to improve our understanding of the impact of the COVID-19 outbreak on the diagnosis of patients with skin cancer and conduct a scoping review to identify whether routine skin cancer diagnoses are affected by the persistent incidence of COVID-19. METHODS AND ANALYSIS: The structure of research was compiled using Population/Intervention/Comparison/Outcomes/Study Design and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. First, we will find the main keywords to capture scientific studies related to the impact of the COVID-19 pandemic on the diagnosis of skin cancer: COVID-19 and skin neoplasms. To warrant sufficient coverage and identify potential articles, we will search the combination of four electronic databases PubMed/MEDLINE, Scopus, Web of Science and EMBASE, and ProQuest from 1 January 2019 until 30 September 2022. The screening, selection and data extraction of studies will be performed by two independent authors, who will then assessed the quality of the included studies according to Newcastle-Ottawa Scale. ETHICS AND DISSEMINATION: As this study will be a systematic review without human participants' involvement, no formal ethical assessment is required. Findings will be presented at conferences related to this field and will be disseminated in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022361569.

Granulosa cells from immature follicles exhibit restricted glycolysis and reduced energy production: a dominant problem in polycystic ovary syndrome.

PURPOSE: We hypothesized that immature oocytes are associated with impaired energy production in surrounding granulosa cells (GCs) in polycystic ovary syndrome (PCOS). Thus, this study investigated mitochondrial function, determined expression of glycolytic regulatory enzymes, and measured ATP levels in GCs of PCOS patients. METHODS: GCs were isolated from forty-five PCOS patients and 45 control women. Intracellular concentration of reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), the rate of glycolysis, total antioxidant capacity (TAC), activities of catalase (CAT) and superoxide dismutase (SOD), and ATP level were measured in GCs. The gene expression and protein levels of glycolytic enzymes (hexokinase, muscular phosphofructokinase, platelet derived phosphofructokinase, and muscular pyruvate kinase) were determined. Association of GC energy level with oocyte maturation was further validated by measuring glycolysis rate and ATP level in GCs isolated from mature and immature follicles from new set of fifteen PCOS patients and 15 controls. RESULTS: PCOS patients showed higher ROS level, decreased TAC, reduced CAT and SOD activities, and lower Δψm together with reduced expression of key glycolytic enzymes. ATP concentration and biochemical pregnancy were lower in PCOS compared with control group. ATP levels were found to be significantly correlated with ROS and Δψm (r = - 0.624 and r = 0.487, respectively). GCs isolated from immature follicles had significantly lower ATP levels and rate of glycolysis compared with the GCs separated from mature follicles in both PCOS patients and control. CONCLUSION: Declined energy due to the mitochondrial dysfunction and restrained glycolysis in GCs is associated with the immature oocytes and lower biochemical pregnancy in PCOS.

Production of anti-tetanus toxin IgY and study of its protective effects in a mouse model.

Tetanus is an acute and often fatal infectious disease caused by Clostridium tetani. Tetanus toxin (TT) is responsible for spastic paralysis observed in tetanus. Anti-tetanus antibodies obtained from horses and humans are the most antitoxins used for tetanus treatment, although some clinical side effects and disadvantages have been reported in their application. The aim of this study is the production of anti-TT IgY and evaluation of its protective effects in a mouse model. Anti-TT IgY was purified from the egg yolk using PEG6000 precipitation and water dilution methods, and its purity was verified by SDS-PAGE. Finally, the potency of purified anti-TT IgY in neutralizing the lethal effects of TT was studied in vivo using a mouse model. PEG6000 precipitation method had better results. Animal studies showed that the purified IgY neutralized the toxic effects of 100 MLD of TT and multiple intravenous-dose injections of anti-TT IgY also had a continuous effect of TT neutralization. The purified anti-TT IgY was effective in neutralizing the lethal activity of TT in a mouse model. Our results suggested that IgY could be an alternative therapeutic source for the management of tetanus in the future.Abbreviations Anti-TT, Anti-tetanus toxin; ELISA, Enzyme-linked immunosorbent assay; IgY, Immunoglobulin Y; MLD, Minimum lethal dose; PBS, Phosphate buffer solution; PEG, Polyethylene glycol; SDS-PAGE, Sodium dodecyl sulfate polyacrylamide gel electrophoresis; TIG, Tetanus immune globulin; TT, Tetanus toxin; WD, Water dilution; RT, Room temperature.

The Association of Mitochondrial Translocator Protein and Voltage-Dependent Anion Channel-1 in Granulosa Cells with Estradiol Levels and Presence of Immature Follicles in Polycystic Ovary Syndrome.

Background: Granulosa cells (GCs) play key roles in oocyte maturation by providing required estradiol (E2). Since the presence of immature oocytes has been reported in cases with polycystic ovary syndrome (PCOS), in this study, the levels of mitochondrial membrane transporter proteins involved in E2 synthesis were determined. E2 concentration and parameters of oxidative status were also measured in follicular fluids of PCOS women. Methods: Forty-three women with PCOS and 43 healthy women who were candidates for IVF procedure due to their husbands' infertility were enrolled in this case-control study. The gene expression and protein levels of mitochondrial translocator protein (TSPO) and voltage-dependent anion channel 1 (VDAC1) were determined in GCs using RT-qPCR and immunocytochemistry assay, respectively. E2 level was measured with electrochemiluminescence, whereas total cholesterol, total antioxidant capacity (TAC), total oxidant status (TOS), and malondialdehyde (MDA) were determined using colorimetric methods in follicular fluids. Data were analyzed using unpaired t-test or Mann-Whitney U test, and Spearman's correlation coefficient. Results: VDAC1 and TSPO were significantly lower in mRNA (p<0.05) and protein levels (p<0.001) of PCOS patients. PCOS patients had lower cholesterol, estradiol, and TAC levels, and higher TOS and MDA contents. E2 level had direct correlation with VDAC1, TSPO, and TAC while it was negatively correlated with TOS, oxidative stress index (OSI), and MDA (p<0.001). Higher E2 levels were associated with higher numbers of high-quality oocytes and conceived embryos (p<0.001). Conclusion: Decreased E2 levels and increased oxidative stress in the follicular fluid may be the cause of immature oocytes in PCOS cases.

Monitoring of synthetic insecticides resistance and mechanisms among malaria vector mosquitoes in Iran: A systematic review.

BACKGROUND: In Iran, the prospect of malaria control relies mainly on insecticides used against the genus Anopheles (Diptera: Culicidae) as important vectors of malaria, arboviruses, and so on. Only eight out of 30 malaria mosquito vectors (Anopheles species) have been examined for insecticide resistance in Iran. This study aimed to review articles related to the incremental trend in insecticide resistance and their mechanisms among anopheline malaria vectors in Iran. METHODS: A literature review was conducted based on such search engines as Iran doc, Web of Science, SID, PubMed, Scopus, and Google Scholar websites using the following keywords: "Anopheles," "Malaria," "Resistance," "Vectors," "Insecticide Resistance," and "Iran" for data collection. Published papers in English or Persian covering 1980 to 2020 were reviewed. RESULTS: A total of 1125 articles were screened, only 16 of which were filtered to be pertinent in this review. While most of the mosquito vectors of malaria, such as Anopheles stephensi, were resistant to DDT, dieldrin, malathion, and becoming less susceptible to deltamethrin and other synthetic pyrethroid insecticides, few like Anopheles fluviatilis s. l. were susceptible to all insecticides. A disseminating trend in insecticide resistance among different anopheline mosquito vector species was evident. Metabolic and insecticide target-site resistance mechanisms were involved with organochlorines and pyrethroids, respectively. CONCLUSIONS: Insecticide resistance is becoming a severe scourge to the effectiveness of vector-borne disease management measures. This event is especially critical in developing and marginalized communities that applied chemical-based vector elimination programs for malaria; therefore, it is crucial to monitor insecticide resistance in malaria vectors in Iran using biochemical and molecular tools.

Protective effects of cerium oxide nanoparticles in non-alcoholic fatty liver disease (NAFLD) and carbon tetrachloride-induced liver damage in rats: Study on intestine and liver.

BACKGROUND AND AIMS: Nanoparticles could represent a therapeutic approach for the treatment of various diseases. It has been reported that cerium oxide nanoparticles (CeO2 NPs) have potential useful effects. Therefore, we aimed to examine the protective effects of the CeO2 NPs in two models of liver injury, non-alcoholic fatty liver disease (NAFLD) and carbon tetrachloride (CCl4)-induced liver fibrosis, in rats. METHODS: In this experimental study, male rats were randomly divided into different experimental groups including: Experiment 1; group1: healthy rats received normal saline, 2: CCl4 group, 3: CCl4 + nanoparticle. Experiment 2; group1: healthy rats received chow diet, 2: NAFLD group, 3: NAFLD + nanoparticle. The oxidative stress markers were determined in the liver and intestine. Tumor necrosis factor-α (TNF-α) levels were measured by ELISA. Histopathological changes of liver and intestine were evaluated by light microspore. RESULTS: Total antioxidant capacity (TAC) and glutathione (GSH) levels significantly decreased, while malondialdehyde (MDA) and total oxidant status (TOS) were significantly increased in the liver, and intestine of the NAFLD and CCl4 group compared with control rats. However, the use of nanoparticles significantly normalized these markers. The levels of the TNF-α were significantly reduced in the nanoparticle group as compared with NAFLD model and CCl4-treated rats. CeO2 NPs also normalized the liver and intestinal histological changes. CONCLUSIONS: Our finding revealed that CeO2 NPs has potential protective effects by increasing antioxidant activity, and reducing inflammation.

Favorable effects of Anethum graveolens on liver oxidative stress and cholesterol 7 alpha-hydroxylase levels in non-alcoholic fatty liver disease (NAFLD) rat models.

BACKGROUND: High-fat high-cholesterol diet induces a phenotype similar to non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) in humans. In NAFLD and NASH, cholesterol and bile acid metabolisms are impaired to accumulate lipids and toxic bile acids along with cholestatic hepatic damage. Recently, the use of herbal-derived cholesterol lowering products has attracted much attention as possible therapeutic strategies for NAFLD. Hence, the aim of this study was to determine the effects of an Anethum graveolens (dill) on liver cholesterol 7 alpha-hydroxylase and liver fat accumulation in rats. METHOD: Thirty-six rats were randomly divided into 6 groups (n = 6) and received normal diet (ND) or a mixture of chow diet+2% cholesterol+0.5% cholic acid + 20% corn oil as high cholesterol/fat (HC-HF) diet (NAFLD model). Animals were also treated daily with dill tablet or dill extract (300 mg/kg). At the end of the 30 days experiments, serum and liver lipid profile and liver total antioxidant capacity were determined. Cholesterol 7 alpha-hydroxylase mRNA and protein expression levels were determined in the liver and histopathological changes in liver tissues were analyzed by microscope. RESULTS: Lipid profiles significantly decreased in dill treated groups (p < 0.05). Liver total antioxidant capacity significantly (p < 0.05) increased and MDA levels markedly (p < 0.05) reduced both in dill tablet and dill extract treated groups (p < 0.05). Both types of treatments caused significant increases in liver cholesterol 7 alpha-hydroxylase gene expression (p < 0.05). Histopathological examinations showed that treatment with dill normalized the hypercholesterolemia-induced changes in liver histology. CONCLUSION: Administration of dill significantly reduced liver fat, oxidative stress and increased cholesterol 7 alpha-hydroxylase enzyme at the both mRNA and protein levels. Dill extract was found more effective than its commercially available tablet.

COVID-19 vaccines: Current evidence and considerations.

The coronavirus disease 2019 (COVID-19) pandemic is a global crisis, with devastating health, business and social impacts. Vaccination is a safe, simple, and effective way of protecting a person against COVID-19. By the end of August 2021, only 24.6% of the world population has received two doses of a COVID-19 vaccine. Since the emergence of COVID-19, several COVID-19 vaccines have been developed and approved for emergency use. Current vaccines have shown efficacy with low risk of adverse effects. However, COVID-19 vaccines have been related to a relatively small number of cases of heart inflammation, anaphylaxis (allergic reactions), and blood clots formation. On the other hand, COVID-19 vaccination is not recommended for children less than 12 years of age. Furthermore, It has been proposed that some new variants (e.g., Lambda and Delta) are proficient in escaping from the antiviral immunity elicited by vaccination. Herein we present current considerations regarding the COVID-19 vaccines including: efficacy against new variants, challenges in distribution, disparities in availability, dosage gender and race difference, COVID-19 vaccine transport and storage, limitations in children and pregnant women. Long-time monitoring is essential in order to find vaccine efficacy and to rule out related side effects.

Diabetes and COVID-19: Mechanism of pneumonia, treatment strategy and vaccine.

As of August 5, 2021, there were about 200,000,000 global confirmed patients of COVID-19, with more than 4,250,000 deaths. The COVID-19 disease which is a tremendous public health threat, jumps unpredictably and outbreaks very quickly. The overall mortality rate of COVID-19 infection is 1%-15% but reaches up to 17-38% in older cases with chronic disorders and in intensive care unit (ICU) subjects. Diabetic patients, particularly those whose disease is not well controlled can be more susceptible to COVID-19. Although diabetes was present in 5.3%-42.3% of fatalities from COVID-19, the underlying pathophysiological mechanisms of action of novel coronavirus in diabetic patients are unknown. Based on the elevating of global prevalence, diabetes is the main medical problem associated with COVID-19. It is plausible that diabetes can forecast elevated severity of pneumonia. The mortality of lung infection among diabetes is remarkably higher compared with non-diabetic patients. Mechanisms responsible for severe pneumonia in the diabetic patients as well as treatment of diabetic patients infected with COVID-19 are largely speculative. Hence, this paper will summarize the recent findings related to the mechanisms of pneumonia and treatment strategies in diabetic patients.

Molecular Monitoring of Knockdown Resistance in Head Louse (Phthiraptera: Pediculidae) Populations in Iran.

Knockdown resistance (kdr) is a common mechanism of insecticide resistance in head lice to the conventionally used pyrethroid pediculosis and can be the result of various amino acid substitutions within the voltage-sensitive sodium channel (VSSC). In this study, 54 sequences from varied specimens were investigated to monitor well-known resistance mutations and probable new mutations. The Pediculus humanus capitis de Geer specimens were collected from 13 provinces in Iran. The specimens were stored in 70% ethanol until DNA extraction and PCR amplification of ~900-bp fragment of VSSC. The sequences were analyzed using different bioinformatics software for the detection of well-known kdr substitutions and additional mutations potentially associated with kdr resistance in head lice. There were six new and an old (haplotype I) kdr haplotypes within the Iranian head louse population. K794E, F815I, and N818D amino acid substitutions were reported for the first time. The P813H mutation was the most prevalent amino acid substitution in eight provinces. Among 53 sequences, 26 (49%) were homozygous susceptible, and 27 (51%) were heterozygotes. Thus, 51% of the head lice collected in Iran harbored only the P813H allele. The exact test for the Hardy-Weinberg (H-W) equilibrium showed that genotype frequencies differed significantly from the expectation in East-Azerbaijan and Tehran provinces. Moreover, these populations had an inbreeding coefficient (Fis) <0, indicating the excess of heterozygotes. This observation suggests that the populations of head lice from Iran are currently under active selective pressure. For the rest of the populations, H-W equilibrium and the expectations were significantly in harmony. The results of the current study highlight molecular techniques in the accurate detection of resistance genotypes before their establishment within the head louse population. Accurate detection of resistant genotypes seems to be helpful in decision-making on lice control programs and resistance monitoring and management.

Production of IgY polyclonal antibody against diphtheria toxin and evaluation of its neutralization effect by Vero cell assay.

BACKGROUND: Diphtheria is a bacterial disease which is caused by Corynebacterium diphtheriae. The symptoms are due to the diphtheria toxin produced by the bacteria. Antibiotic therapy and the use of diphtheria antitoxin is a recommended strategy to control diphtheria. Although mammalian antibodies are used to treat patients, IgY antibody has advantages over mammalian ones, including cost-effectiveness and production through non-invasive means. Moreover, in contrast to mammalian antibodies, IgY does not bind to the rheumatoid factor and does not activate the complement system. The objective of this study was to evaluate the in vitro neutralizing effect of IgY against diphtheria toxin. RESULTS: Anti-DT IgY was produced by immunization of the laying white leghorn chickens. Indirect enzyme-linked immunosorbent assay revealed successful immunization of the animals, and the IgY was purified with a purity of 93% via polyethylene glycol precipitation method. The neutralizing activity of the purified IgY was evaluated by Vero cell viability assay. This assay confirmed that 1.95 µg (8.6 µg/ml of culture medium) of anti-DT IgY would neutralize 10 fold of cytotoxic dose 99% of DT, which was 0.3 ng (1.33 ng/ml of culture medium). CONCLUSION: This anti-DT IgY may be applicable for diphtheria treatment and quality controls in vaccine production.

Biological properties the novel application of N-trimethyl chitosan nanospheres as a stabilizer and preservative in tetanus vaccine.

PURPOSE: Chitosan is a natural polymer that has excellent properties include biocompatibility, biodegradability, no cytotoxicity, high charge density, low cost, mucoadhesive, permeation enhancing (ability to cross tight junction), and immunomodulating ability that makes the spectrum of its applicability much broader. This study was conducted to investigate the stabilizing, preservative and immunogenicity properties of N-trimethyl chitosan nanospheres (N-TMCNS). MATERIALS AND METHODS: The tetanus toxoid (TT) was encapsulated into N-TMCNS and then characterized by scanning electron microscope, atomic force microscope, and dynamic light scattering. For stabilizer assay of N-TMCNS after storage of TT-N-TMCNS at different temperatures for 3 weeks, they were used for immunization of mice and different temperatures groups' anti-TT-N-TMCNS production compared with other groups. Finally, the immunized mice were challenged with tetanus toxin. The preservation activity of TT-N-TMCNS against Escherichia coli was compared with thimerosal formulated TT. RESULTS: Our results revealed that heat-treated TT-N-TMCNS could induce higher titer of neutralizing immunoglobulin G in compared to TT vaccine and was able to protect the mice better than TT vaccine in challenge test. Furthermore, N-TMCNS as a preservative inhibited the growth of E. coli more effective than thimerosal. CONCLUSION: Overall, the obtained results indicated that the N-TMCNS is one of the best stabilizer and preservative agent that can be used in the formulation of TT vaccine.

Contribution of Fc fragment of monoclonal antibodies to tetanus toxin neutralization.

BACKGROUND: Monoclonal antibodies (MAbs) against neurotoxin of Clostridium tetani are considered as a novel source of immunoglobulins for passive immunotherapy of tetanus. Toxin neutralization is classically attributed to the Fab and F(ab')2 fragments of antibodies. Herein, we generated Fab and F(ab')2 fragments of three toxin neutralizing mouse MAbs and compared their neutralizing activities to those of their intact molecules. METHODS: Fab and F (ab')2 fragments of the antibodies were generated by papain and pepsin digestions, respectively, and their toxin neutralizing activities were compared with those of the intact antibodies in an in vivo toxin neutralization assay. RESULTS: While low doses of the intact MAbs were able to fully protect the mice against tetanus toxin, none of the mice which received Fab or F(ab')2 fragments survived until day 14, even at the highest administered dose. All mice receiving human polyclonal anti-tetanus immunoglobulin or their fragments were fully protected. CONCLUSION: Reduction in toxin neutralization activities of Fab and F(ab')2 fragments of our MAbs seems to be influenced by their Fc regions. Steric hindrance of the Fc region on the receptor-binding site of the toxin may explain the stronger neutralization of the toxin by the intact MAbs in comparison to their fragments.

Diversity of Arthropods in Municipal Solid Waste Landfill of Urmia, Iran.

The present study was designed for identification of arthropods species in Urmia city municipal solid waste (MSW) landfill in 2014. The specimens were collected by hand and with sweep net. After the initial classification at the order level, genus and species identification were done using morphological identification keys. In total, 1,913 arthropod samples were collected. The samples were classified into four different classes. The most abundant species of arachnids was Steatoda paykulliana Walckenaer (Araneae: Theridiidae) and Agelenopsis spp. Giebel (Araneae: Agelenidae). Out of nine insect orders, Coleoptera, Diptera, and Hymenoptera were the most prevalent, all of which include medically important species. Sixteen families and 25 genera of insects were collected, including the muscid genera, Musca, Muscinia, Phannia, and Stomoxys. Musca, Psyllabora, and Phania were the most prevalent insect genera. In total, 33 species of arthropods were collected from MSW landfill in Urmia. Five insect species were heterometabolic including medically important species, Periplaneta americana Linnaeus (Blattodea: Blattidae) and Shelfordella lateralis Walker (Blattodea: Ectobiidae). Determination of the fauna in MSW landfill will be helpful in the control of possible vector borne disease epidemics.

Variation of Housekeeping Genes in Clinical Isolates and Vaccine Strains of Bordetella pertussis.

BACKGROUND: Bordetella pertussis causes serious contagious infections, primarily in childhood. A whole-cell vaccine, diphtheria-tetanus-whole cell pertussis (DTwP), has been used to protect against pertussis in children in Iran, but the pertussis cases have been increasing during recent years. We determined the allelic variation level of housekeeping genes in isolates recovered from pertussis patients and vaccine strains used in national vaccination program. METHODS: Five clinical isolates, 2 vaccine strains and a Tohama I strain were studied through multilocus sequence typing (MLST) of housekeeping genes. The relatedness between STs, the founder, single- and double-locus variants (SLVs, DLVs) was determined using eBURST algorithm. The concordance between the type assignments by MLST and PFGE was determined. RESULTS: In the 5 clinical isolates, 2 STs were identified, ST2 and ST79. The vaccine strains displayed two distinct allelic profiles assigned to ST1 and ST2. ST2 was predicted as founder and the remaining STs were SLVs of ST2. MLST and PFGE type assignments were 86.6% concordant. CONCLUSIONS: The clinical isolates of B. pertussis were different from vaccine strains used in the national vaccination program. This study confirms the low level of variation in housekeeping genes of B. pertussis. MLST of virulent antigenic genes needs to be applied as a complementary method for the characterization of new ST-harboring isolates that may predominate periodically. The combination of these data allows rapid and efficient surveillance of currently circulating isolates. These data might elucidate the future trends and considerations for vaccine formulation and design.