Efficacy of Setarud (IMod), a novel drug with potent anti-toxic stress potential in rat inflammatory bowel disease and comparison with dexamethasone and infliximab

The inflammatory bowel disease (IBD) is an idiopathic, immune-mediated and chronic intestinal condition. In the present study, the effect of Setarud (IMOD), a novel natural drug with known immunomodulatory, anti-inflammatory and antioxidant properties was investigated in experimental colitis in rats and compared with the dexamethasone and infliximab. Immunologic colitis was induced by intracolonic administration of a mixture of trinitrobenzene sulfonic acid (TNBS) and absolute ethanol in male Wistar rats. Animals were divided into 6 groups of sham (normal group), control (vehicle-treated), positive control (dexamethasone 1 mg/kg/day given orally and infliximab 5 mg/kg/day given subcutaneously) and 3 Setarud-treated groups (13.3, 20, 30 mg/kg/day given intraperitoneally). The treatment continued for 14 consecutive days and then animals were decapitated on the day 15 and distal colons were removed for macroscopic, microscopic, and biochemical assays. Biochemical markers, including TNF-alpha, IL-1beta, ferric reducing/antioxidant power (FRAP), myeloperoxidase (MPO) activity and thiobarbitoric acid-reactive substance (TBARS) were measured in the homogenate of colonic tissue. A remarkable reduction in macroscopic and histological damage scores was observed in the animals treated with Setarud. These findings were confirmed by decreased levels of TNF-alpha, interleukin-1beta, MPO activity and TBARS, and raised levels of FRAP in the colon tissue. These observations confirmed the immunomodulatory, anti-inflammatory and antioxidant properties of Setarud in experimental colitis, which was comparable to those of dexamethasone and infliximab.     

Expression Patterns of ABC Transporter Genes in Fluconazole-Resistant <Emphasis Type="Italic">Candida glabrata</Emphasis>

Clinical management of fungal diseases is compromised by the emergence of antifungal drug resistance in fungi, which leads to elimination of available drug classes as treatment options. An understanding of antifungal resistance at molecular level is, therefore, essential for the development of strategies to combat the resistance. This study presents the assessment of molecular mechanisms associated with fluconazole resistance in clinical Candida glabrata isolates originated from Iran. Taking seven distinct fluconazole-resistant C. glabrata isolates, real-time PCRs were performed to evaluate the alternations in the regulation of the genes involved in drug efflux including CgCDR1, CgCDR2, CgSNQ2, and CgERG11. Gain-of-function (GOF) mutations in CgPDR1 alleles were determined by DNA sequencing. Cross-resistance to fluconazole, itraconazole, and voriconazole was observed in 2.5 % of the isolates. In the present study, six amino acid substitutions were identified in CgPdr1, among which W297R, T588A, and F575L were previously reported, whereas D243N, H576Y, and P915R are novel. CgCDR1 overexpression was observed in 57.1 % of resistant isolates. However, CgCDR2 was not co-expressed with CgCDR1. CgSNQ2 was upregulated in 71.4 % of the cases. CgERG11 overexpression does not seem to be associated with azole resistance, except for isolates that exhibited azole cross-resistance. The pattern of efflux pump gene upregulation was associated with GOF mutations observed in CgPDR1. These results showed that drug efflux mediated by adenosine-5-triphosphate (ATP)-binding cassette transporters, especially CgSNQ2 and CgCDR1, is the predominant mechanism of fluconazole resistance in Iranian isolates of C. glabrata. Since some novel GOF mutations were found here, this study also calls for research aimed at investigating other new GOF mutations to reveal the comprehensive understanding about efflux-mediated resistance to azole antifungal agents.     

Reduction of diabetes-induced oxidative stress by phosphodiesterase inhibitors in rats

Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. The aim of this study was to investigate the effect of different phosphodiesterase inhibitors on lipid peroxidation and total antioxidant capacity (TAC) of plasma in streptozotocin-induced diabetic rats (Rattus norvegicus). Rats became diabetic by a single administration of streptozotocin (STZ, 45 mg/kg). The effects of 15-days treatment by milrinone, sildenafil, and theophylline as cyclic-AMP and -GMP phosphodiesterase inhibitors (PDEIs) on diabetes-induced oxidative stress were studied. The levels of glucose, malonedialdehyde (MDA) the by product of lipid peroxides, and TAC (FRAP test) were estimated in plasma of control and experimental groups of rats. A significant increase in the levels of plasma glucose, and MDA and a concomitant decrease in the levels of TAC were observed in diabetic rats. These alterations were reverted back to near normal level after the treatment with PDEIs. Treatment of diabetic rats by PDEIs reduced MDA levels and increased TAC in the order of milrinone>sildenafil>theophylline. In conclusion, the present investigation show that PDIS possesses antioxidant activities, which may be attributed to their enhancing effect on cellular cyclic nucleotides contributing to the protection against oxidative stress in streptozotocin-induced diabetes. Exact mechanism of protective actions of cAMP- and cGMP-phosphodiesterase remains to be elucidated by further studies. This finding may suggest a place for PDEIs in maintaining health in diabetes.     

Subclassification of localized Leishmania lymphadenitis in fine needle aspiration smears

OBJECTIVE: To describe the cytologic findings of localized Leishmania lymphadenitis and discuss the differential diagnosis. STUDY DESIGN: The study group consisted of 133 cases. All of them were diagnosed by fine needle aspiration (FNA) study. The ages ranged between 3 and 80 years, 102 were male and 31 female. Seventy lymph nodes were excised. RESULTS: The FNA smears revealed a polymorphic population of cells composed of lymphocytes, histiocytes, giant cells, abnormal plasma cells and tingible body macrophages. Leishman-Donovan (LD) bodies were identified in all cases, but their number differed from case to case. Granulomas, dendritic cells, mast cells and lymphoglandular bodies were identified in a substantial number of cases. Depending upon the presence of characteristic cytologic findings, the cases were divided into five major groups: acute inflammation with giant cells, histiocytic granulomas, epithelioid cell granulomas, plasma cell type and mixed histioplasmacytic type. CONCLUSION: Leishmaniasis is an uncommon cause of cervical lymphadenitis but should be considered in the differential diagnosis of unexplained lymphadenopathy in endemic countries. Demonstration of LD bodies is necessary for the diagnosis of this self-limited condition, for which no treatment is required.     

Characterization of the major histocompatibility complex locus association with Beh?et’s disease in Iran

IntroductionThe aim of this study was to characterize the association of human leukocyte antigen (HLA) B alleles and major histocompatibility complex (MHC) single nucleotide polymorphisms (SNPs) with Behçet’s disease (BD) in an Iranian dataset.MethodsThe association of three SNPs in the MHC region previously identified as the most associated in high-density genotyping studies was tested in a case–control study on 973 BD patients and 825 controls from Iran, and the association of HLA-B alleles was tested in a subset of 681 patients and 414 controls.ResultsWe found that HLA-B*51 (P = 4.11 × 10⁻⁴¹, OR [95% CI] = 4.63[3.66-5.85]) and B*15 confer risk for BD (P = 2.83 × 10⁻², OR [95% CI] = 1.75[1.08-2.84]) in Iranian, and in B*51 negative individuals, only the B*15 allele is significantly associated with BD (P = 2.51 × 10⁻³, OR [95% CI] = 2.40[1.37-4.20]). rs76546355, formerly known as rs116799036, located between HLA-B and MICA (MHC class I polypeptide-related sequence A), demonstrated the same level of association with BD as HLA-B*51 (P_adj = 1.78 × 10⁻⁴⁶, OR [95% CI] = 5.46[4.21-7.09], and P_adj = 8.34 × 10⁻⁴⁸, OR [95% CI] = 5.44[4.20-7.05], respectively) in the HLA-B allelotyped subset, while rs2848713 was less associated (P_adj = 7.14 × 10⁻³⁵, OR [95% CI] = 3.73[2.97-4.69]) and rs9260997 was not associated (P_adj = 1.00 × 10⁻¹). Additionally, we found that B*51 genotype-phenotype correlations do not survive Bonferroni correction, while carriers of the rs76546355 risk allele predominate in BD cases with genital ulcers, positive pathergy test and positive BD family history (2.31 × 10⁻⁴ ≤ P ≤ 1.59 × 10⁻³).ConclusionsWe found that the HLA-B*51 allele and the rs76546355/rs116799036 MHC SNP are independent genetic risk factors for BD in Iranian, and that positivity for the rs76546355/rs116799036 risk allele, but not for B*51, does correlate with specific demographic characteristics or clinical manifestations in BD patients.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0585-6) contains supplementary material, which is available to authorized users.     

A Monte Carlo study on dose distribution validation of GZP6 60Co stepping source

Aim

Stepping source in brachytherapy systems is used to treat a target lesion longer than the effective treatment length of the source. Cancerous lesions in the cervix, esophagus and rectum are examples of such a target lesion.

Background

In this study, the stepping source of a GZP6 afterloading intracavitary brachytherapy unit was simulated using Monte Carlo (MC) simulation and the results were used for the validation of the GZP6 treatment planning system (TPS).

Materials and methods

The stepping source was simulated using MCNPX Monte Carlo code. Dose distributions in the longitudinal plane were obtained by using a matrix shift method for esophageal tumor lengths of 8 and 10 cm. A mesh tally has been employed for the absorbed dose calculation in a cylindrical water phantom. A total of 5 × 10⁸ photon histories were scored and the MC statistical error obtained was at the range of 0.008–3.5%, an average of 0.2%.

Results

The acquired MC and TPS isodose curves were compared and it was shown that the dose distributions in the longitudinal plane were relatively coincidental. In the transverse direction, a maximum dose difference of 7% and 5% was observed for tumor lengths of 8 and 10 cm, respectively.

Conclusion

Considering that the certified source activity is given with ±10% uncertainty, the obtained difference is reasonable. It can be concluded that the accuracy of the dose distributions produced by GZP6 TPS for the stepping source is acceptable for its clinical applications.     

Correction to: Variation in Blood and Colorectal Epithelia’s Key Trace Elements along with Expression of Mismatch Repair Proteins from Localized and Metastatic Colorectal Cancer Patients

Biological Trace Element Research - The original version of this article unfortunately contained a mistake. The name of “Ali Ghorbani Ranjbary” is now corrected in the author group of...     

Effects of carbon source,polyethylene glycol and abscisic acid on secondary embryo induction and maturation in rapeseed (<Emphasis Type="Italic">Brassica napus</Emphasis> L.) microspore-derived embryos

In this study, the effects of carbon sources, abscisic acid (ABA) either alone or in combination with polyethylene glycol (PEG) were evaluated on secondary embryo (SE) induction and maturation in rapeseed microspore-derived embryos (MDE) of cultivars Global, PF₇₀₄ and Option. Among various carbon sources tested (sucrose, glucose, fructose and sorbitol), the use of 0.3 M (300 mOsml⁻¹) glucose and 0.2 M (200 mOsml⁻¹) sorbitol in SE induction medium (for cultivars Global and PF₇₀₄) and sorbitol at 0.2 and 0.3 M (200 and 300 mOsml⁻¹, for cultivar Option), induced the highest secondary embryogenesis percentage (%SE). The highest number of SEs per each MDE (SE/MDE) was observed with 0.2 M (200 mOsml⁻¹) sorbitol in cultivar Global and with 0.3 M (300 mOsml⁻¹) glucose in cultivars PF₇₀₄ and Option. In another part of this study, the effect of different concentrations of ABA (0, 20, 40, 60, 80 and 100 μM) and of a combined use of ABA (0 and 40 μM) and PEG 4000 or PEG 6000 at 15 g l⁻¹ (3.75 and 2.5 mOsml⁻¹, respectively) was examined on induction and maturation of SEs. In the first experiment, the use of ABA in SE induction medium reduced the mean number of SE/MDE in the three studied cultivars, whereas use of 40–80 μM ABA in SE induction medium increased the percentage of mature SEs in each cultivar. The combined use of PEG with or without ABA also reduced the mean number of SE/MDE compared with control, but resulted in significant enhancement of the percentages of mature SEs for the three cultivars.