Sulforaphane Reduces SAMHD1 Phosphorylation To Protect Macrophages from HIV-1 Infection.

The cellular protein SAMHD1 is important for DNA repair, suppressing LINE elements, controlling deoxynucleoside triphosphate (dNTP) concentrations, maintaining HIV-1 latency, and preventing excessive type I interferon responses. SAMHD1 is also a potent inhibitor of HIV-1 and other significant viral pathogens. Infection restriction is due in part to the deoxynucleoside triphosphatase (dNTPase) activity of SAMHD1 but is also mediated through a dNTPase-independent mechanism that has been described but not explored. The phosphorylation of SAMHD1 at threonine 592 (T592) controls many of its functions. Retroviral restriction, irrespective of dNTPase activity, is linked to unphosphorylated T592. Sulforaphane (SFN), an isothiocyanate, protects macrophages from HIV infection by mobilizing the transcription factor and antioxidant response regulator Nrf2. Here, we show that SFN and other clinically relevant Nrf2 mobilizers reduce SAMHD1 T592 phosphorylation to protect macrophages from HIV-1. We further show that SFN, through Nrf2, triggers the upregulation of the cell cycle control protein p21 in human monocyte-derived macrophages to contribute to SAMHD1 activation. We additionally present data that support another, potentially redox-dependent mechanism employed by SFN to contribute to SAMHD1 activation through reduced phosphorylation. This work establishes the use of exogenous Nrf2 mobilizers as a novel way to study virus restriction by SAMHD1 and highlights the Nrf2 pathway as a potential target for the therapeutic control of SAMHD1 cellular and antiviral functions. IMPORTANCE Here, we show, for the first time, that the treatment of macrophages with Nrf2 mobilizers, known activators of antioxidant responses, increases the fraction of SAMHD1 without a regulatory phosphate at position 592. We demonstrate that this decreases infection of macrophages by HIV-1. Phosphorylated SAMHD1 is important for DNA repair, the suppression of LINE elements, the maintenance of HIV-1 in a latent state, and the prevention of excessive type I interferon responses, while unphosphorylated SAMHD1 blocks HIV infection. SAMHD1 impacts many viruses and is involved in various cancers, so knowledge of how it works and how it is regulated has broad implications for the development of therapeutics. Redox-modulating therapeutics are already in clinical use or under investigation for the treatment of many conditions. Thus, understanding the impact of redox modifiers on controlling SAMHD1 phosphorylation is important for many areas of research in microbiology and beyond.

Prevalence of HIV, hepatitis B virus, and hepatitis C virus among incarcerated people in Iran: a systematic review and meta-analysis.

OBJECTIVES: Incarcerated people are at higher risk for HIV, Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) infections. This review systematically summarized the evidence on the prevalence of these infections among incarcerated people in Iran. STUDY DESIGN: A systematic review and meta-analysis. METHODS: We searched Embase, PubMed, Web of Science, Scopus, PsychInfo, Iranian databases, including IranMedex, Magiran, Scientific Information Database (SID), and IranDoc. A grey literature review was conducted to find unpublished reports from the Ministry of Health and experts throughout the country. Included studies reported data on the prevalence of HIV, HBV, or HCV infections. A random-effects meta-analysis was performed to estimate the pooled prevalence. A meta-regression analysis was also conducted. RESULTS: Of 1461 screened records, 23 records were eligible (total participants = 199,855). The pooled prevalence of HIV (17 studies), HBV (6 studies), and HCV (10 studies) was 2.77% (95% CI: 1.96, 3.70), 2.89% (95% CI: 2.28, 3.56), and 21.57% (95% CI: 13.62, 30.76), respectively. Meta-regression analyses showed that HIV (P-value = 0.05) and HCV (P-value = 0.02) were reduced over time using survey year as the interested variable in the model. Also, lifetime history of drug injection had a significant association with the HIV infection (P-value = 0.03). CONCLUSION: The findings suggest that the prevalences of these infections are relatively considerable among Iranian incarcerated people. These findings support developing interventions to reduce the risk of the acquisition and circulation of these infections among incarcerated people, and continued harm reduction programs among most at-risk incarcerated people, as well as HCV treatment.

Sex out of marriage and condom use among homeless youth in Iran.

OBJECTIVES: Sexual behaviors of homeless youth in Iran have not been well studied. This study aimed to measure the frequency and associated factors of sex out of marriage and condom use among homeless youth in Kerman, Iran. STUDY DESIGN: In this cross-sectional study, we recruited 202 homeless youth (age: 15-29 years who experienced 30 or more days of homelessness in the last 12 months) from 11 street locations between September to December 2017. METHODS: Of 202 participants, 169 (83.7%) reported sex in the last 12 months and were include in this analysis. We assessed the prevalence of sex out of marriage in the last 12 months, condom use in last sex, and then evaluated their covariates in multivariable logistic regression analysis. RESULTS: The prevalence of sex out of marriage was 19.6% (95% confidence intervals [CIs]: 13.8%, 26.3%) and the prevalence of condom use was 43.8% (95% CI: 36.2%, 51.6%). Sex out of marriage was significantly correlated with male gender (adjusted odds ratio [AOR]: 24.38; 95% CI: 3.1-192.1) and being unmarried (AOR: 5.94; 95% CI: 2.3-15.5). Condom use was significantly correlated with male gender (AOR: 2.16; 95% CI: 1.1-4.2) and higher educational status (AOR: 4.30; 95% CI: 2.1-8.8). CONCLUSION: Our findings indicate that one in five homeless youth had sex out of marriage, and less than half did no use condom. These should be addressed by adapting education and harm reduction programs targeting this specific population in Iran.

HSP90 inhibitor enhances anti-proliferative and apoptotic effects of celecoxib on HT-29 colorectal cancer cells via increasing BAX/BCL-2 ratio.

Due to the high prevalence and mortality rate of colorectal cancer (CRC), new treatment approaches like combination therapy seem to be necessary. The relationship between chronic inflammation and colorectal cancer development and progression has been shown to be important. Celecoxib, a selective COX-2 inhibitor, is the only non-steroidal anti-inflammatory drug (NSAID) that has been approved for cancer therapy and prevention. Because of cardiovascular side effects of COX-2 inhibitors, combination therapy may improve the therapeutic profile. 17-Demethoxy-17-allylamino geldanamycin (17-AAG), a heat shock protein 90 (HSP90) inhibitor, shows anti-inflammatory effects via down-regulation of the key mediators of inflammation such as Nuclear Factor κB (NF-kB), JAK/Signal Transducer and Activator of Transcription (JAK/STAT). Thus, we studied the effect(s) of combination of 17-AAG and celecoxib on HT-29 cells viability and apoptosis induction. Based on MTT results, we showed an increase in the inhibitory effect of celecoxib when combined with 17-AAG, especially at low a concentration of celecoxib.  Flow cytometry analysis demonstrated that apoptosis induction is probably the mechanism of additive inhibitory effects of 17-AAG and celecoxib combination. To explore the possible mechanism of apoptosis induction by 17-AAG and celecoxib combination, levels of BAX and BCL-2 proteins were determined by western blotting. The BAX/BCL-2 ratio in the combination group was increased compared to 17-AAG or celecoxib alone, mainly via decreasing BCL-2 levels. In conclusion, 17-AAG, increased inhibitory effects of celecoxib on HT-29 cells, probably by induction of apoptosis.

The CLRX.1/NOD24 (NLRP2P) pseudogene codes a functional negative regulator of NF-κB, pyrin-only protein 4.

Pseudogenes are duplicated yet defunct copies of functional parent genes. However, some pseudogenes have gained or retained function. In this study, we consider a functional role for the NLRP2-related, higher primate-specific, processed pseudogene NLRP2P, which is closely related to Pyrin-only protein 2 (POP2/PYDC2), a regulator of nuclear factor-κB (NF-κB) and the inflammasome. The NLRP2P open-reading frame on chromosome X has features consistent with a processed pseudogene (retrotransposon), yet encodes a 45-amino-acid, Pyrin-domain-related protein. The open-reading frame of NLRP2P shares 80% identity with POP2 and is under purifying selection across Old World primates. Although widely expressed, NLRP2P messenger RNA is upregulated by lipopolysaccharide in human monocytic cells. Functionally, NLRP2P impairs NF-κB p65 transactivation by reducing activating phosphorylation of RelA/p65. Reminiscent of POP2, NLRP2P reduces production of the NF-κB-dependent cytokines tumor necrosis factor alpha and interleukin (IL)-6 following toll-like receptor stimulation. In contrast to POP2, NLRP2P fails to inhibit the ASC-dependent NLRP3 inflammasome. In addition, beyond regulating cytokine production, NLRP2P has a potential role in cell cycle regulation and cell death. Collectively, our findings suggest that NLRP2P is a resurrected processed pseudogene that regulates NF-κB RelA/p65 activity and thus represents the newest member of the POP family, POP4.

CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X.

The Human Immunodeficiency Virus (HIV) encodes several proteins that contort the host cell environment to promote viral replication and spread. This is often accomplished through the hijacking of cellular ubiquitin ligases. These reprogrammed complexes initiate or enhance the ubiquitination of cellular proteins that may otherwise act to restrain viral replication. Ubiquitination of target proteins may alter protein function or initiate proteasome-dependent destruction. HIV Viral Protein R (Vpr) and the related HIV-2 Viral Protein X (Vpx), engage the CRL4-DCAF1 ubiquitin ligase complex to target numerous cellular proteins. In this review we describe the CRL4-DCAF1 ubiquitin ligase complex and its interactions with HIV Vpr and Vpx. We additionally summarize the cellular proteins targeted by this association as well as the observed or hypothesized impact on HIV.

Modulation of the hepatocyte rough endoplasmic reticulum single chloride channel by nucleotide-Mg2+ interaction.

The effect of nucleotides on single chloride channels derived from rat hepatocyte rough endoplasmic reticulum vesicles incorporated into bilayer lipid membrane was investigated. The single chloride channel currents were measured in 200/50 mmol/l KCl cis/trans solutions. Adding 2.5 mM adenosine triphosphate (ATP) and adenosine diphosphate (ADP) did not influence channel activity. However, MgATP addition inhibited the chloride channels by decreasing the channel open probability (Po) and current amplitude, whereas mixture of Mg(2+) and ADP activated the chloride channel by increasing the Po and unitary current amplitude. According to the results, there is a novel regulation mechanism for rough endoplasmic reticulum (RER) Cl(-) channel activity by intracellular MgATP and mixture of Mg(2+) and ADP that would result in significant inhibition by MgATP and activation by mixture of Mg(2+) and ADP. These modulatory effects of nucleotide-Mg(2+) complexes on chloride channels may be dependent on their chemical structure configuration. It seems that Mg-nucleotide-ion channel interactions are involved to produce a regulatory response for RER chloride channels.

Comparison of some dietary habits on corrosion behavior of stainless steel brackets: an in vitro study.

BACKGROUND AND OBJECTIVE: Resistance to corrosion is an advantageous property of orthodontic brackets; however, due to low levels of pH found in the mouth of a patient, localized corrosion may occur This can affect tooth movement by increasing friction between the arch wire and bracket slot and initiate enamel discoloration. Additionally, corrosion causes the release of elements that may lead to cytotoxic and biological side effects. The aim of this study was to compare the amount of corrosion caused by lemon juice, vinegar and Coca-Cola on orthodontic brackets in vitro and then to recommend the most suitable diet during orthodontic treatment. METHOD: Sixty orthodontic brackets in three groups of twenty were immersed in a test solution (Fusamaya-Meyer artificial saliva plus lemon juice, vinegar or Coca-Cola) at a temperature of 37 degrees C +/- 1. Moreover, a negative control consisting of twenty brackets were put in pure artificial saliva. After 6 weeks the amount of corrosion was determined by measuring delta W of mean weights of brackets and the results were analyzed by general linear models (repeated measurement). RESULTS: Significant differences were seen during different weeks of the study (P < 0.001) and different solutions (P < 0.001). This study showed the amount of corrosion in orthodontic brackets was the most for cola followed by vinegar and then lemon juice. In addition, mean differences for cola versus lemon juice was -0.010 (sig. <0.001), vinegar versus lemon juice was -0.006 (sig. = 0.001) and cola versus vinegar was -0.004 (sig. = 0.013). CONCLUSION: Acidic effervescent soft drinks such as cola have to be eliminated or minimized in the nutritional diet of orthodontic patients because of their harmful effects on their brackets.

Identification and Determination of the Geographical Distribution of Freshwater Snails in Lorestan, Iran.

Snails are creatures present in various ecosystems that, in addition to being present in human surroundings, some of them are also important in veterinary medicine and medicine as the intermediate hosts of Digenean trematodes. The present study was conducted to identify and determine the geographical distribution of freshwater snails and investigate the relationship of variables, such as season and geographical region, with snail species and dispersion in Lorestan in the west of Iran. A total of 4400 samples of freshwater snails were collected using the multistage sampling method (i.e., stratified, cluster, and randomized) from 110 points in five geographical regions in four seasons and then identified based on their morphological characteristics by diagnostic keys. The ArcGIS software (version 10.3) was used to evaluate the spatial distribution of the freshwater snails. In this study, seven species of freshwater snails were identified in six families belonging to six genera, namely Melanopsis doriae (6.30% of the variation in species), Theodoxus doriae (5.55%), Bithynia tentaculata (43.22%, the dominant species), Physa acuta (24.98%), Lymnaea truncatula (9.75%), Gyraulus euphraticus (8.18%), and Lymnaea gedrosiana (2.02%). The geographic distribution of freshwater snails was recorded across five regions in 22 points per region for every season. The spatial distribution maps showed that the distribution of freshwater snails varies according to region and season (P&lt;0.001). The obtained results revealed the effects of season and geographical region on the distribution and population density of snails in the province. These data can be used for the implementation of control programs against parasitic diseases in the region, including trematodes.

Bovine subclinical ketosis in dairy herds in Iran.

Subclinical ketosis (SCK) is defined as elevated concentrations of ketone bodies in the absence of clinical signs of ketosis. It is an important metabolic disease in dairy cattle during early lactation and is associated with losses in milk production and several other periparturient diseases. Limited information is available regarding the prevalence of SCK in dairy herds in Iran. The objectives of this study were (i) to determine the incidence of SCK in the dairy herds in Kerman province of Iran using serum beta-hydroxybutyrate (BHB) concentrations, and (ii) to investigate the relationship between serum concentrations of BHB and glucose of cows with SCK. In the present study, 90 multiparous Holstein cows (4-6 years old) from 11 commercial dairy herds were evaluated 3-4 weeks after calving. The distribution of blood BHB concentrations seemed to suggest a cut-off point of 1200 micromol/L between cows with and without SCK. At this cut-off point, 14.4% of tested cows (13/90) were classified as subclinically ketotic, with the prevalence rate within herd ranging from 10% to 20%. Cows with SCK were detected in all the investigated dairies except one. Blood glucose concentrations in cows with SCK were significantly lower (p < or = 0.05) than in cows without SCK, and serum BHB and glucose concentration were inversely correlated (r = -0.43, p < or = 0.05). The results suggest that, using a cut-off of 1200 micromol/L, BHB concentrations can be used during early lactation for diagnosis and to make management decisions for prevention and treatment.

Prevalence of smoking among high-school students of Tehran in 2003.

This study in 2003 determined the prevalence of smoking and its associated factors among high-school students in Tehran, Islamic Republic of Iran. Out of 1095 students aged 14-18 years, 29% (31% boys, 26% girls) were occasional and 5% (6% boys and 2% girls) daily smokers. Among occasional smokers, 21% had family members who also smoked, whereas for students who had never tried smoking, no family members smoked. Of 316 occasional smokers, 12% lived with a single parent compared with only 5% of never smokers. Regression analysis showed that significant risk factors for daily smoking were: having a brother or sister who smokes (OR = 8.58) and having more than 1 family member who smokes (OR = 6.33).

Changes in the Concentration of Ions in Saliva and Dental Plaque after Application of CPP-ACP with and without Fluoride among 6-9 Year Old Children.

STATEMENT OF PROBLEM: The casein phospho peptide-amorphous calcium phosphate with or without fluoride (CPP-ACPF and CPP-ACP respectively) are of considerably new materials which are highly recommended for prevention of dental caries. However, there is a shortage in literature on how they affect the ion concentration of saliva or dental plaque. OBJECTIVES: The aim of this study was to evaluate the concentration of calcium, phosphate and fluoride in the plaque and saliva of children with Early Childhood Caries (ECC) after applying the CPP-ACP paste in comparison with the use of CPP-ACPF paste. MATERIALS AND METHODS: One ml of un-stimulated saliva of 25 preschool children was collected and then 1 mg of the plaque sample was collected from the buccal surfaces of the two first primary molars on the upper jaw. CPP-ACP as well as CPP-ACPF pastes were applied on the tooth surfaces in two separate steps. In steps, plaque and saliva sampling was performed after 60 minutes. The amount of calcium ions was measured by Atomic Absorption Device and the amount of phosphate and fluoride ions was measured by Ion Chromatography instrument. Data were analyzed using Repeated Measurements ANOVA at a p < 0.05 level of significance. RESULTS: Application of both CPP-ACPF and CPP-ACP significantly increased the concentration of calcium, phosphate, and fluoride in both saliva and dental plaque. Moreover, significantly higher salivary fluoride concentration was seen after application of CPP-ACPF compared to CPP-ACP. No other significant difference was observed between these two materials. CONCLUSIONS: CPP-ACPF can be more useful than CPP-ACP in protecting the primary teeth against caries process, especially when there is poor hygiene.

Prevalence of antibiotic resistance and genetic relatedness of Escherichia coli isolates in HIV and thalassemia patients in southeastern Iran.

The present study was carried out to evaluate the prevalence of antibiotic resistance genes in Escherichia coli isolates from HIV and thalassemia patients and to determine the phylogenetic group distribution and to genotype the isolates in southeastern Iran. This cross-sectional study was performed in E. coli isolates taken from fecal and urine samples of 43 HIV and 62 thalassemia patients. The E. coli isolates were examined for 13 antibiotic resistance genes and determine the phylogroups. The Rep-PCR DNA fingerprinting method was utilized to determine the genotype of the isolates. Among the 105 E. coli isolates, 66.7% isolates were positive for qnrS, 55.2% for dhfrI, 40.9% for sulI, 33.3% for sulII and 31.4% for blaTEM genes. A blaCTX-M-15 gene was detected in 20.9% isolates, aac(3)-I in 14.3% isolates and aadA in 12.4% isolates, whereas blaSHV and qnrB genes were identified in 10.5% and 8.6% isolates, respectively. Out of the isolates, only 2.8% isolates possessed the blaOXA-1 gene, and no IMP and VIM genes were detected. The significant phylogroup was A (37.2%), B2 (15.3%), B1 and unknown (each 14.3%), D (13.4%) and C, F and clade I (each 2%). Phylogroup A accounted for the highest antibiotic resistance. The results of Rep-PCR indicated that the isolates were closely related. These results showed a high prevalence of genes encoding antibiotic resistance in the E. coli isolates. The majority of E. coli isolates distributed among phylogroup A, whereas positive isolates for antibiotic resistance genes were disseminated among various phylogroups (A, B2, and D).

The prevalence of ovine Eimeria infection in Rudsar, North of Iran, (2011-2012).

This study was undertaken to determine the prevalence of Eimeria infection in sheep in Rudsar, North of Iran, in period of 1 year (March 2011 to March 2012). The samples (approximately 3-5 grams of faeces) were collected from the rectum of 270 sheep and transferred to the parasitology laboratory. Eimeria species were identified following sporulation of faeces in a thin layer of 2.5 % potassium dichromate for one or 2 weeks at 27 °C. Out of 270 faecal samples examined, 170[(63.0 %; 95 % Confidence Interval (CI) 56.9-68.7)] were positive for Eimeria spp. Five species of Eimeria, including E. ahsata, E. ovina, E. crandallis, E. parva and E. ovinoidalis were identified in faecal samples by modified McMaster technique. The most frequent species was E. crandallis. Sheep were considered in four age groups (less than 1 year old, 1-2 years old, 2-3 years old and over 3 years old).The results also indicated that less than 1 year old sheep have greater infection ratio as compare with older animals. Female had significantly higher prevalence of Eimeria than male. Higher infection was seen in females compare to males and in winter compare to summer. Parasitological gross and microscopic examinations revealed Eimeria infection is common in sheep of Rudsar, North Iran.

Tick diversity and detection of Coxiella burnetii in tick of small ruminants using nested Trans PCR in Southeast Iran.

Ticks are obligatory bloodsucking arthropods, and probably the most harmful ectoparasites that may cause some tick born diseases. The main objective of this study was to determine the prevalence, diversity and seasonal distribution of ticks and using a nested Trans PCR to identify Coxiella burnetii in ticks collected from small ruminants in Sistan and Balouchestan province, southeast Iran. A total 1305 ticks were collected from 272 Sheep and 253 Goats during May 2014 to April 2015. Prevalence of ixodid tick infestation in small ruminants was 58.4%. Of all examined ticks, nine tick species were identified as follow: Hyalomma anatolicum anatolicum (30.3%), Rhipicephalus sanguineus (21%), Hyalomma anatolicum excavatum (19%), Rhipicephalus turanicus (9%), Rhipicephalus bursa (6.7%), Hyalomma detritum (4.7%), Hyalomma dromedarii (4.4%), Hyalomma asiaticum asiaticum (4.4%) and Hyalomma marginatum (0.5%). The nested Trans PCR examination of ixodid ticks revealed that Hyalomma anatolicum anatolicum and Rhipicephalus sanguineus were infected with C. burnetii. The results of the present study revealed that ixodid ticks infestation was widespread and shows their role as putative vectors and reservoirs for this pathogenic agent in southeast Iran. Hence; Q fever should be considered a significant public health threat in this region.

HSP90 Inhibition Suppresses PGE2 Production via Modulating COX-2 and 15-PGDH Expression in HT-29 Colorectal Cancer Cells.

The existence of multiple-interactive roles between several signaling pathways in tumorigenesis shows the significance of pharmacological factors like heat shock protein 90 (HSP90) inhibitors which control several signaling pathways simultaneously. HSP90 as a molecular chaperone supports the active conformational structure and function of several oncogenic signal proteins, termed "client" proteins, some of them act as a link between cancer and inflammation. Prostaglandin E2 (PGE2) is one of the major mediators of inflammation in colorectal cancer development and progress. However, the relationship between chaperone activity of HSP90 and PGE2 levels remains unclear. We evaluated the inhibitory effects of 17-demethoxy-17-allylamino geldanamycin (1 7-AAG), an HSP90 inhibitor, on PGE2 levels in HT-29 colorectal cancer cells. For the first time, we showed inhibitory effects of 17-AAG, on PGE2 levels in HT-29 colorectal cancer cells. 17-AAG inhibited PMA-induced cyclooxygenase-2 (COX-2) mRNA expression and protein level. We showed 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression induced by 17-AAG treatment at both mRNA and protein levels. In conclusion, we found that inhibitory effects of 17-AAG on PGE2 levels in HT-29 colorectal cancer cells were mediated through modulating COX-2 and 15-PGDH expression.

Effect of Chronic Administration of Buspirone and Fluoxetine on Inflammatory Cytokines in 6-Hydroxydopamine-lesioned Rats.

Neuro-inflammation in Parkinson's disease (PD) is associated with glial cell activation and production of different inflammatory cytokines. In this study we investigated the effect of chronic administration of buspirone and fluoxetine on cerebrospinal fluid (CSF) levels of inflammatory cytokines, TNF-α, IL-1ß and IL-6 in 6-hydroxydopamine (6-OHDA)-lesioned rats.6-OHDA (8 µg/2 µl/rat) was injected unilaterally into the central region of the substantia nigra pars copmacta (SNc) and after 21 days lesioned rats were treated with buspirone and fluoxetine intraperitonealy (i.p.) for 10 days. CSF samples were collected at tenth day of drugs administration and were analysed by ELISA method to measure TNF-α, IL-1ß and IL-6 levels.The results showed that the CSF levels of TNF-α was increased 3 weeks after 6-OHDA injection while there was a significant decrease in TNF-α levels of parkinsonian animals treated with buspirone (1 mg/kg) and fluoxetine (1 mg/kg). IL-1ß and IL-6 both were decreased in parkinsonian rats, while their level was increased in buspirone (1 mg/kg) and fluoxetine (1 mg/kg) treated parkinsonian rats.Our study indicates that chronic administration of buspirone and fluoxetine in 6-OHDA-lesioned rats restores central concentration of inflammatory cytokines to the basal levels. We suggest that serotonergic agents can be used as adjuvant therapy along with commonly used anti-parkinsonian drugs by modulation of cerebral inflammatory cytokines. We suggest that the further clinical investigations may be carried out to prove this hypothesis.

Polypharmacy-induced drug-drug interactions; threats to patient safety.

Patient safety is an increasingly recognized challenge and opportunity for stakeholders in improving health care delivery. Because of extensive use of medicines, life expectancy is increasing and elderly as well as comorbidities need polypharmacy, and therefore the risk of drug-drug interactions (DDIs) increases.We searched PubMed and ScienseDirect for epidemiology of articles describing the frequency of potential DDIs published up to 2011 in title, abstract, keywords and text.Studies show that the rate of DDIs both in outpatients and hospitalized patients is high. The elderly, <5 year-old children and women are at higher risks for it. Also, the rate of DDIs in patients who suffer from chronic kidney disease (CKD), cardiovascular disease (CVD) such as heart failure (HF) and hypertension (HTN) and cancers is significant.Physicians, for lowering the risk of DDIs, should take precise drug history, prescribe appropriate and lowest drugs and ultimately counsel with clinical pharmacologist as a key strategy in order to insure the patient safety. This article reviews the existing data concerning this problem to provide an aid for choosing the appropriate drugs and prescribe the most effective with the lowest DDIs for providing patient safety.

A cross-sectional study of the seroprevalence and flock-level factors associated with ovine and caprine brucellosis in southeastern Iran.

This cross-sectional study was conducted to estimate seroprevalence and to identify flock-level factors associated with seropositivity to brucellosis in small ruminants in Kerman province, southeastern Iran. In October-November 2011, serum samples were randomly collected from 1767 sheep and 1233 goats, older than 18 months, from 300 flocks. The sera were initially screened for the presence of anti-Brucella antibodies using the Rose-Bengal test; those found to be positive were then examined by Wright and 2-mercaptoethanol Brucella agglutination tests. A questionnaire was used to collect data on flock-level factors likely associated with the within flock seroprevalence of brucellosis. The associations were statistically evaluated for significance in multivariable logistic models. Sixty three flocks (21.00%; 95% CI: 16.80-26.60) had at least one seropositive animal. The mean within-flock seroprevalence was 3.10% (95% CI: 2.60-3.90). The presence of newly purchased animals (OR=3.42; 95% CI: 1.35-8.65) was significantly associated with seropositivity. Our findings highlight the role of animal movement among flocks in the epidemiology of brucellosis in this region. Thus, a control program for brucellosis in the region is suggested to impose appropriate restrictions on animal trade and improve knowledge of livestock owners about quarantine principles for newly purchased animals.

Characterization of tumor heterogeneity using dynamic contrast enhanced CT and FDG-PET in non-small cell lung cancer.

PURPOSE: Dynamic contrast-enhanced CT (DCE-CT) quantifies vasculature properties of tumors, whereas static FDG-PET/CT defines metabolic activity. Both imaging modalities are capable of showing intra-tumor heterogeneity. We investigated differences in vasculature properties within primary non-small cell lung cancer (NSCLC) tumors measured by DCE-CT and metabolic activity from FDG-PET/CT. METHODS: Thirty three NSCLC patients were analyzed prior to treatment. FDG-PET/CT and DCE-CT were co-registered. The tumor was delineated and metabolic activity was segmented on the FDG-PET/CT in two regions: low (<50% maximum SUV) and high (≥50% maximum SUV) metabolic uptake. Blood flow, blood volume and permeability were calculated using a maximum slope, deconvolution algorithm and a Patlak model. Correlations were assessed between perfusion parameters for the regions of interest. RESULTS: DCE-CT provided additional information on vasculature and tumor heterogeneity that was not correlated to metabolic tumor activity. There was no significant difference between low and high metabolic active regions for any of the DCE-CT parameters. Furthermore, only moderate correlations between maximum SUV and DCE-CT parameters were observed. CONCLUSIONS: No direct correlation was observed between FDG-uptake and parameters extracted from DCE-CT. DCE-CT may provide complementary information to the characterization of primary NSCLC tumors over FDG-PET/CT imaging.