The effects of functionalization of carbon nanotubes on toxicological parameters in mice.

Carbon nanotubes (CNTs) have emerged as a new class of multifunctional nanoparticles in biomedicine, but their multiple in vivo effects remain unclear. Also, the impact of various functionalization types and duration of exposures are still unidentified. Herein, we report a complete toxicological study to evaluate the effects of single- and multiwalled carbon nanotubes (SWCNTs and MWCNTs) with either amine or carboxylic acid (COOH) surface functional groups. The results showed that significant oxidative stress and the subsequent cell apoptosis could be resulted in both acute and, mainly, in chronic intravenous administrations. Also, male reproductive parameters were altered during these exposures. The amino-functionalized CNTs had more toxic properties compared with the COOH functionalized group, and also, in some groups, the multiwalled nanotubes were more active in eliciting cytotoxicity than the single-walled nanotubes. Interestingly, the SWCNTs-COOH had the least alterations in most of the parameters. Evidently, it is concluded that the toxicity of CNTs in specific organs can be minimized through particular surface functionalizations.

IL-10 IS DOWN-REGULATED IN THE CARDIOVASCULAR DISEASES SUSPECTED PATIENTS, INDEPENDENT OF ANGIOGRAPHY. / RIVEN' IL-10 ZNYZhENYY̆ U PATsIIeNTIV IZ SERTsEVO-SUDYNNYMY ZAKhVORIuVANNIaMY, NEZALEZhNO VID PROVEDENNIa ANGIOGRAFIChNYKh DOSLIDZhEN'.

IL-10 and interferon-gamma (IFN-γ) are the important anti and pro-inflammatory cytokines, respectively, which may participate in the cardiovascular disease pathogenesis. Additionally, environmental factors, such as the X-ray, can modulate cytokine expression. Due to the fact that X-ray is used during angiography, hence, angiography may alter expression of the cytokines. OBJECTIVE: Accordingly, this project was aimed to assess IL-10 and IFN-γ serum levels within cardiovascular patients (with and without vessel stenosis) versus healthy controls and also the effects of angiography on the serum levels of the cytokines. MATERIAL AND METHODS: This study was performed on the 80 participants, including twenty cases in each group (healthy controls and cardiovascular patients without vessel stenosis, stenosis of 1 vessel and stenosis of more than 1 vessel) to evaluate IL-10 and IFN-γ serum levels using ELISA technique. The IL-10 and IFN-γ serum levels also compared within group 2, 3 and 4 before and after angiography to explore the effects of the technique on the IL-10 and IFN-γ serum levels. RESULTS: IL-10, but not IFN-γ, serum levels were higher in the healthy controls than all cardiovascular patients. IL-10 and IFN-γ serum levels were not altered after angiography and also were not differ in the smoker versus non- smoker and opium consuming versus non-opium consuming participants. CONCLUSION: Due to the results it may be concluded that IL-10 can be considered as a plausible inhibitor of cardio- vascular diseases independent of angiography duration and X-ray, however, IFN-γ has no effects in the Iranian patients suffering from cardiovascular diseases.

Decompressive hemicraniectomy without clot evacuation in supratentorial deep-seated intracerebral hemorrhage.

OBJECTIVE: Decompressive craniectomy (DC) lowers intracranial pressure and improves outcomes in patients with malignant middle cerebral artery stroke; yet, its usefulness in intracerebral hemorrhage (ICH) is unclear. The authors sought to assess the preliminary utility of decompressive hemicraniectomy (DHC) without clot evacuation in patients with deep-seated supratentorial ICH. PATIENTS AND METHODS: Patients with deep seated spontaneous ICH who were admitted to the Golestan Hospital, of Ahvaz, from November 2014 to February 2016, were prospectively enrolled in this study. A prospective clinical trial where 30 patients diagnosed having large hypertensive ICH was randomly allocated to either group A or B using permuted-block randomization. These patients (n = 30), who all had large deep seated supratentorial ICH with surgery indications, were randomly divided to two groups. ultimately, in one group (n = 13), large DHC was performed without clot evacuation, while in the other (n = 17), craniotomy with clot evacuation was done. Data pertaining to the patients' characteristics and treatment outcomes were prospectively collected. RESULTS: There was no statistically significant difference between two treatment groups (P > 0.05). No significant difference was observed between the two groups in terms of mortality and GOS at 6 months (P > 0.05); nevertheless, the good outcome (Glasgow Outcome Scale = 4-5) for patients with hematoma evacuation was slightly higher (35.3%) as compared to the DHC patients without clot evacuation (30.7%). CONCLUSION: Decompresive craniectomy without clot evacuation in deep seated ICH can be accomplished with identical mortality and outcome in comparison to patient that undergone clot evacuation.

In vitro reprotoxicity of carboxyl-functionalised single- and multi-walled carbon nanotubes on human spermatozoa.

Reproductive toxicity of carboxyl-functionalised carbon nanotubes (CNT-COOH), as the most commonly used form of water-soluble CNTs, is not clearly studied. The aim of this study was to investigate in vitro toxicity of carboxylated single-walled and multi-walled CNTs (SWCNT-COOH and MWCNT-COOH) against human spermatozoa. Sperm cells from healthy donors were incubated with 0.1-100 µg/ml of SWCNT-COOH or MWCNT-COOH at 37°C for up to 5 hr. Viability of sperm cells was assessed using MTT test, and sperm motility was evaluated following World Health Organization guideline. Production of reactive oxygen species (ROS) and nitric oxide (NO) in sperm was also assessed. We showed that both MWCNT-COOH and SWCNT-COOH following incubation in vitro with human spermatozoa did not exert negative effect on viability while motility was significantly (p < .05) dropped in a dose-dependent manner. Moreover, there was no significant effect of the type, dose and exposure time of the CNT-COOH on NO production. Exposure of sperm cells to both examined types of CNTs at concentrations as low as 0.1 µg/ml caused a significant increase in ROS levels. In conclusion, carboxylated forms of CNTs seem to be harmful for human spermatozoa. Further studies, especially using in vivo models, are needed to decide about reprotoxicity of carboxylated forms of CNTs.

Inflammatory and anti-inflammatory cytokines in the seminal plasma of infertile men suffering from varicocele.

Varicocele is one of causes of the declined sperm quality and low sperm production, which can lead to infertility in males. There are several experimental and epidemiological findings which support the idea that inflammatory mechanisms play an essential role in varicocele pathogenesis. Besides, in this pathological state, interleukin-37 (IL-37) as an anti-inflammatory cytokine is able to bind interleukin-18-binding protein (IL-18BP), and subsequently binds IL-18 receptor ß, inhibiting the pro-inflammatory activity of IL-18. To explore the interaction between IL-37 and IL-18 in infertility, we measured the amount of these cytokines in the seminal fluid of infertile men affected by varicocele. The seminal plasma levels of IL-37 and IL-18 were measured in 75 infertile men with varicocele and 75 healthy fertile controls (age range, 30-48 years) using enzyme-linked immunosorbent assay. The seminal levels of IL-37 and IL-18 were significantly increased in infertile men with varicocele when compared to fertile controls (p < .0001). Because of the essential role(s) of cytokines in inflammatory response of cell systems, it could be possible that sperm motility is reduced following increased IL-18, activated neutrophils and reactive oxygen species in semen of infertile patients with varicocele. Moreover, the results of this study indicated that interaction between IL-37 and IL-18Rß can lead to reduced inflammatory responses. It seems that IL-37 might be a potential biomarker and therapeutic target for male infertility.

The Comparison of Biodistribution, Efficacy and Toxicity of Two PEGylated Liposomal Doxorubicin Formulations in Mice Bearing C-26 Colon Carcinoma: a Preclinical Study.

BACKGROUND: Over the past several years, the considerable attention has been progressively given to liposomal formulations of anthracyclines. SinaDoxosome(®) (Exir Nano Sina Company, Iran) is a pegylated liposomal doxorubicin (DOX) which approved by Food and Drug Administration of IRAN for treatment of some types of cancer. The aim of this study was to compare the biodistribution, efficacy, cardiotoxicity and hepatotoxicity of SinaDoxosome(®) with Caelyx(®) in mice bearing C-26 colon carcinoma. METHODS AND RESULTS: Mice tumor size evaluation during the experimental period (28 days) showed comparable therapeutic efficacy of nano-formulations. The biodistribution studies showed no significant difference in DOX tissue concentration between Caelyx(®) and SinaDoxosome(®). DOX induced-ECG changes were not detected in nano-formulations. No significant alteration was found in biochemical indexes of myocardial injury in mice exposed to nano-formulations in comparison with control mice. The tissue oxidative parameters such as lipid peroxidation, glutathione, catalase and superoxide dismutase was significantly changed as the results of free DOX treatment. However, the oxidative status of Caelyx(®) and SinaDoxosome(®) treated animals did not showed any changes. The experiment also revealed that apoptotic pathway was not activated in the heart of mice exposed to nano-formulations. CONCLUSIONS: Although this investigation showed that Caelyx(®) and SinaDoxosome(®) are similar in terms of biodistribution, efficacy and toxicity, appropriate clinical evaluations in patients should be considered.

Predicting CCHF incidence and its related factors using time-series analysis in the southeast of Iran: comparison of SARIMA and Markov switching models.

Crimean-Congo haemorrhagic fever (CCHF) is endemic in the southeast of Iran. This study aimed to predict the incidence of CCHF and its related factors and explore the possibility of developing an empirical forecast system using time-series analysis of 13 years' data. Data from 2000 to 2012 were obtained from the Health Centre of Zahedan University of Medical Sciences, Climate Organization and the Veterinary Organization in the southeast of Iran. Seasonal autoregressive integrated moving average (SARIMA) and Markov switching models (MSM) were performed to examine the potential related factors of CCHF outbreaks. These models showed that the mean temperature (°C), accumulated rainfall (mm), maximum relative humidity (%) and legal livestock importation from Pakistan (LIP) were significantly correlated with monthly incidence of CCHF in different lags (P < 0·05). The modelling fitness was checked with data from 2013. Model assessments indicated that the MSM had better predictive ability than the SARIMA model [MSM: root mean square error (RMSE) 0·625, Akaike's Information Criterion (AIC) 266·33; SARIMA: RMSE 0·725, AIC 278·8]. This study shows the potential of climate indicators and LIP as predictive factors in modelling the occurrence of CCHF. Our results suggest that MSM provides more information on outbreak detection and can be a better predictive model compared to a SARIMA model for evaluation of the relationship between explanatory variables and the incidence of CCHF.

Protective effects of curcumin and vitamin E against chlorpyrifos-induced lung oxidative damage.

There are increasing concerns regarding the toxic effects of chlorpyrifos (CPF) on human health. Curcumin (CUR) is a yellow pigment isolated from turmeric ground rhizome of Curcuma longa Linn., which has been identified as an antioxidant agent. This study was designed to examine the protective effect of CUR and vitamin E (Vit E) on CPF-induced lung toxicity. Rats were divided into seven groups: control, CPF (13.5 mg/kg, orally), CPF + CUR (100 and 300 mg/kg, respectively, orally), CPF + α-tocopherol (Vit E, 150 mg/kg, intraperitoneally), CPF and CUR (100 and 300 mg/kg, respectively) in combination with α-tocopherol. The regimens were administered once daily for 28 days. At the end of the treatment period, lungs were collected for evaluation of oxidative factors and histopathological parameters. CUR and Vit E led to a decrease in lipid peroxidation in the lungs of the CPF-injected animals (48% and 51%, respectively). Glutathione peroxidase inhibited by CPF (91.9 nmol/min/mg protein) was induced again by CUR and Vit E (167.1 and 171.8 nmol/min/mg protein). CUR and Vit E caused a significant induction of superoxide dismutase (103.4 U/mg protein). Catalase activity almost returned to normalcy in CPF-intoxicated rats subjected to CUR + Vit E treatment (p < 0.001). Lung sections from CPF-treated rats displayed histopathological damages, while coadministration of CUR and Vit E resulted in apparently normal morphology with a significant decrease in injuries (p < 0.05). Our findings revealed that coadministration of Vit E and CUR to CPF-treated animals prevents the oxidative damages in the lung tissues.

Seroepidemiology of crimean congo hemorrhagic Fever in slaughterhouse workers in north eastern iran.

BACKGROUND: Crimean Congo Hemorrhagic Fever (CCHF) is an acute febrile haemorrhagic disease. This study was conducted to ascertain the infection status amongst slaughterhouse workers in Iran's north-eastern provinces (Razavi and northern and southern Khorasan), so that analysis of the results could help clarification of the epidemiology of this disease in the aforementioned provinces and eastern regions of Iran. METHODS: In this cross-sectional study, conducted in 2004 and 2005, 108 slaughterhouse workers from 24 cities of the three previously mentioned provinces were randomly entered into the study. An IgG specific ELISA test was carried out on the participants' serum samples. RESULTS: Sixteen out of 108 (14.8%) participants under study were shown to have IgG against CCHF. The highest rate of infection was seen in Razavi Khorasan and southern Khorasan at 17.5% and 16.7%, respectively. CONCLUSION: The study showed a relatively high frequency of this disease amongst slaughterhouse workers in these provinces. Taking into account the small number of reported cases from these provinces, it would seem that more focus is required on primary diagnosis and on referral of suspected patients.

Phylogenetic analysis in a recent controlled outbreak of Crimean-Congo haemorrhagic fever in the south of Iran, December 2008.

Crimean-Congo haemorrhagic fever (CCHF) is a viral zoonotic disease with a high mortality rate in humans. The CCHF virus is transmitted to humans through the bite of Ixodid ticks or contact with blood or tissues of CCHF patients or infected livestock. In December 2008, a re-emerging outbreak of CCHF occurred in the southern part of Iran. Five people were hospitalised with sudden fever and haemorrhaging, and CCHF was confirmed by RT-PCR and serological assays. One of the cases had a fulminant course and died. Livestock was identified as the source of infection; all animals in the incriminated herd were serologically analysed and more than half of them were positive for CCHFV. We demonstrated that two routes of transmission played a role in this outbreak: contact with tissue and blood of infected livestock, and nosocomial transmission. Phylogenetic analyses helped to identify the origin of this transmission. This outbreak should be considered as a warning for the national CCHF surveillance system to avoid further outbreaks through robust prevention and control programmes.

Characterization and testing of periodic mesoporous organosilicas as potential selective benzene adsorbents.

The effects of surface imprinting on the adsorption and desorption properties of benzene- and diethylbenzene-bridged periodic mesoporous organosilicas (PMOs) acting as GC stationary-phase preconcentration sorbents for benzene and xylene were examined. Surface-imprinted and nonimprinted PMOs with diethylbenzene (DEB), benzene (BENZ), and ethane (BTSE) bridges and nonimprinted mesoporous silica (MCM-41) were prepared via well-established surfactant templating synthetic methods. The imprinted materials were synthesized using a surfactant demonstrated to produce trinitrotoluene (TNT) selective sorbents with increased adsorption capacity for cresol and 4-nitrophenol as well as TNT. Powder XRD and nitrogen sorption measurements revealed that all of the materials were mesoporous with the DEB materials having a random pore structure and lower surface area than the other materials which had ordered pore structures. Results for maximum uptake of benzene and p-xylene indicate a small but consistent positive effect on the adsorption of benzene and p-xylene due to surface imprinting. Comparing the surface area normalized uptakes (mg/m(2)) for materials having the same organic bridge with and without imprinting (DEB vs TDMI-DEB and BENZ vs TDMI-BENZ) shows that in seven of eight comparisons the imprinted analogue had a higher aromatic uptake. The imprinted samples showed higher weight normalized uptakes (mg/g) in five of eight cases. When used as a GC stationary phase, the organosilica materials yield more symmetrical chromatographic peaks and better separation than MCM-41, indicating superior trapping of BTX analytes, particularly at low concentrations. Additionally, these materials rapidly desorb the preconcentrated compounds.

Surveillance and laboratory detection system of Crimean-Congo haemorrhagic fever in Iran.

Crimean-Congo haemorrhagic fever (CCHF) is a viral zoonotic disease with a high mortality rate in humans. The CCHF virus (CCHFV) is transmitted to humans through the bite of Ixodid ticks or by contact with blood or tissues of infected livestock. In addition to zoonotic transmission, CCHFV can be spread from person to person and is one of the rare haemorrhagic fever viruses able to cause nosocomial outbreaks in hospitals. Crimean-Congo haemorrhagic fever is a public health problem in many regions of the world such as Eastern Europe, Asia, the Middle East and Africa. In addition to clinical symptoms, the diagnosis of CCHF is based on the use of serological tests for the detection of immunoglobulin M and immunoglobulin G antibodies and on the use of molecular tools such as RT-PCR. From 1970 to 1978, serological and epidemiological studies were performed in humans and in livestock of Iran. After two decades and observations of CCHF in some provinces of Iran, a CCHF surveillance and detection system was established in 1999, leading to a dramatically decreased mortality rate from 20% (year 2000) to 2% (year 2007).

Degradation of phenanthrene and anthracene by Nocardia otitidiscaviarum strain TSH1, a moderately thermophilic bacterium.

AIMS: The metabolism of phenanthrene and anthracene by a moderate thermophilic Nocardia otitidiscaviarum strain TSH1 was examined. METHODS AND RESULTS: When strain TSH1 was grown in the presence of anthracene, four metabolites were identified as 1,2-dihydroxy-1,2-dihydroanthracene, 3-(2-carboxyvinyl)naphthalene-2-carboxylic acid, 2,3-dihydroxynaphthalene and benzoic acid using gas chromatography-mass spectrometry (GC-MS), reverse phase-high performance liquid chromatography (RP-HPLC) and thin-layer chromatography (TLC). Degradation studies with phenanthrene revealed 2,2'-diphenic acid, phthalic acid, 4-hydroxyphenylacetic acid, o-hydroxyphenylacetic acid, benzoic acid, a phenanthrene dihydrodiol, 4-[1-hydroxy(2-naphthyl)]-2-oxobut-3-enoic acid and 1-hydroxy-2-naphthoic acid (1H2NA), as detectable metabolites. CONCLUSIONS: Strain TSH1 initiates phenanthrene degradation via dioxygenation at the C-3 and C-4 or at C-9 and C-10 ring positions. Ortho-cleavage of the 9,10-diol leads to formation of 2,2'-diphenic acid. The 3,4-diol ring is cleaved to form 1H2NA which can subsequently be degraded through o-phthalic acid pathway. Benzoate does not fit in the previously published pathways from mesophiles. Anthracene metabolism seems to start with a dioxygenation at the 1 and 2 positions and ortho-cleavage of the resulting diol. The pathway proceeds probably through 2,3-dicarboxynaphthalene and 2,3-dihydroxynaphthalene. Degradation of 2,3-dihydroxynaphthalene to benzoate and transformation of the later to catechol is a possible route for the further degradation of anthracene. SIGNIFICANCE AND IMPACT OF THE STUDY: For the first time, metabolism of phenanthrene and anthracene in a thermophilic Nocardia strain was investigated.

Characterization of a moderate thermophilic Nocardia species able to grow on polycyclic aromatic hydrocarbons.

AIMS: Our goal was the characterization of a new moderate thermophilic polycyclic aromatic hydrocarbon (PAH)-utilizing Nocardia strain. METHODS AND RESULTS: A thermophilic bacterium, strain TSH1, was isolated from a contaminated soil. The macroscopic and microscopic features fit well with the description of Nocardia species. The results of 16S rRNA gene analysis showed 100% match to the type strain of N. otitidiscaviarum DSM 43242(T). Strain TSH1 showed the same mycolic acid pattern as the type strain of N. otitidiscaviarum but its fatty acid profile did not permit identification to the species level. The carbon utilization profile of strain TSH1 was different from N. otitidiscaviarum. The results of hydrophobicity measurements showed that PAHs-grown cells were significantly more hydrophobic than LB-grown cells. Furthermore, biosurfactant production was detected during bacterial growth on different culture media. CONCLUSIONS: Strain TSH1 is capable of growing on a range of PAHs. When grown in PAHs-supplemented media, strain TSH1 showed a high affinity for the organic phase, suggesting that it can develop a hydrophobic surface. SIGNIFICANCE AND IMPACT OF THE STUDY: High cell surface hydrophobicity and capability of strain TSH1 to degrade different PAHs at 50 degrees C may make it an ideal candidate to treat PAH-contaminated desert soils.

The efficacy of oral ribavirin in the treatment of crimean-congo hemorrhagic fever in Iran.

We compared the mortality rate among patients suspected of having Crimean-Congo hemorrhagic fever (CCHF) who received treatment with oral ribavirin and those who did not. Ninety-seven (69.8%) of 139 treated patients suspected of having CCHF survived, and 61 (88.9%) of 69 treated patients with confirmed CCHF survived. The efficacy of oral ribavirin was 80% among patients with confirmed CCHF and 34% among patients suspected of having CCHF. Considering the limitations of observational studies, we conclude that oral ribavirin is an effective treatment for the hemorrhagic form of CCHF.