Genotype characterization of livestock and human cystic echinococcosis in Mazandaran province, Iran.

Echinococcus granulosus is a helminth from the family Taeniidae, which causes cystic echinococcosis (CE) in humans and diverse livestock around the world. The identification of existing genotypes in different regions is a major step towards the prevention and establishment of control programmes for the disease. This study aimed to detect CE genotypes using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of the internal transcribed spacer-1 (ITS1) gene and sequencing of the cytochrome c oxidase subunit 1 (Cox1) gene in isolates from the central part of Mazandaran province, northern Iran. Forty isolates were collected from sheep, 17 from cattle and 6 from human formalin-fixed paraffin-embedded tissues (FFPE). The ITS1 and Cox1 genes were successfully amplified by PCR in 41 and 42 samples, respectively. PCR-RFLP and sequencing showed that all isolates had the G1-G3 genotypes in this study. Out of 31 isolates subjected to sequencing for the Cox1 gene, 80.7% had the G1 genotype. G2 (16.1%) and G3 (3.2%) genotypes were observed in five sheep and one cattle samples, respectively. Five human isolates were also sequenced for the ITS1 gene, which showed that all samples belonged to the G1 genotype. Ten haplotypes were determined among the isolates by alignment analysis of the Cox1 gene. In summary, this study demonstrated that G1 was the dominant genotype circulating between humans and livestock in the studied region. Furthermore, high genotypic diversity among the CE isolates was observed.

Effect of remote ischemic postconditioning during thrombolysis in STEMI.

BACKGROUND: Remote ischemic postconditioning (RIPC) is suggested to protect the myocardium against ischemia in various settings. However, the effect of RIPC in patients with acute ST-elevation myocardial infarction (STEMI) who undergo thrombolysis has yet to be examined. PATIENTS AND METHODS: In this single-center, randomized controlled trial, we examined the effect of RIPC on the resolution of ST-segment elevation (STR) in response to thrombolysis. Patients in the RIPC group had three cycles of 5­min cuff inflation followed by 5­min deflation to the upper arm. RESULTS: The study comprised 78 patients (15 women), of whom 41 were randomized to the RIPC group and 37 to the control group. STR occurred in 61% of the patients in the RIPC group, while it was detected only in 35% of controls (p = 0.026). Although STR was more common in the RIPC group, there was no difference in the extent of ΣCK-48 h between the two groups. Furthermore, the length of hospital stay and the frequency of adverse events were similar between the RIPC and control groups. CONCLUSION: RIPC during thrombolytic therapy in STEMI was associated with a higher frequency of STR. However, it did not affect enzymatic infarct size or the frequency of adverse events. (Clinical trial registration number: IRCT2014011916229N2.).

Primary ovarian insufficiency with t(5;13): a case report and literature review on disrupted genes.

OBJECTIVES: To report a woman with primary ovarian insufficiency (POI) with reciprocal translocation between chromosomes 5 and 13. METHODS: Chromosomal analysis (G-banding) of a 39-year-old woman with elevated gonadotropin levels and secondary amenorrhea and review of the literature with a special focus on disrupted genes at the reported breakpoints. RESULTS: A reciprocal translocation between the long arms of chromosomes 5 and 13 was identified in the patient (46,XX,t(5;13)(q13;q14)). Investigation of the breakpoints revealed that the 13q14.1 region encompasses FOXO1 (forkhead box 1) gene, which has an important role in granulosa cell function and follicle maturation. CONCLUSIONS: Autosomal translocations are rare in women with POI. We have reported the first case of a de novo reciprocal translocation involving chromosomes 5 and 13 in a POI patient. As one of the breakpoints encompasses the FOXO1 gene, it seems that disruption of this gene can be the cause of POI in this patient. This provides further evidence on the role of autosomal translocations in disrupting POI-associated genes. Therefore, concentrating on the genes at the breakpoints will be helpful to delineate the new biological pathways or genes involved in POI pathogenesis.

Pulmonary hypertension in rheumatic mitral stenosis revisited.

BACKGROUND: In patients with mitral stenosis (MS), pulmonary hypertension (PH) is a significant contributor to the associated morbidity. We aimed to study factors associated with the presence of significant PH (sPH) and whether incorporating body surface area (BSA) in the mitral valve area (MVA) would improve the predictive value of the latter. METHODS: The medical records of 558 patients with severe MS undergoing percutaneous balloon mitral commissurotomy were evaluated over a period of 8 years. Factors associated with the presence of significant PH (sPH) defined as mPAP ≥ 40 mm Hg were examined. RESULTS: A total of 558 patients (423 women) were enrolled. Overall, 153 (27%) patients had sPH. Patients with sPH were similar to the rest of the subjects in terms of demographics, body habitus, blood group, and incidence of atrial fibrillation. Among echocardiographic findings, absolute MVA, indexed MVA, and mean transmitral valve gradient were associated with the presence of sPH. Transmitral valve gradient during right heart catheterization had the highest area under the curve for an association with sPH. CONCLUSION: Age, gender, heart rhythm, and blood group were not associated with the presence of sPH in severe MS. The predictive value of the indexed MVA for the presence of sPH was not higher than that of absolute MVA.

Predicting outcome after percutaneous balloon mitral commissurotomy : Role of neutrophil-lymphocyte ratio.

BACKGROUND: The value of the neutrophil-lymphocyte ratio (NLR) along with the severity of mitral stenosis (MS) in predicting the outcome of percutaneous balloon mitral commissurotomy (PBMC) has not been studied. PATIENTS AND METHODS: Patients with severe MS undergoing PBMC between 2013 and 2014 in a university hospital were prospectively enrolled. Complete blood cell count was obtained upon admission and NLRs were calculated. The correlations between NLR with immediate PBMC success and restenosis in 1 year were evaluated. RESULTS: In all, 102 patients (80 women) with a mean age of 44.5 ± 13.1 years were enrolled in the study. NLR on admission was 2.6 ± 0.8 and mitral valve area (MVA) was 0.89 ± 0.18 cm2. Patients with a lower MVA at baseline had a higher NLR (p = 0.016). The rate of immediate success was 63 % for PBMC. There was no difference in NLR between patients with regard to early and late failures, as well as those who developed restenosis of the valve. Smaller valve area and the rate of valvular dilatation during PBMC were the only independent factors that predicted early and late failure, respectively. CONCLUSION: NLR at the time of treatment was not useful in predicting procedural outcome or restenosis during follow-up of patients undergoing PBMC.

Antioxidant and Anticancer Activities of Walnut (Juglans regia L.) Protein Hydrolysates Using Different Proteases.

Walnut (Juglans regia L.) contains approximately 20-25 % protein with abundant essential amino acids. The enzymatic hydrolysate of Persian walnut (Chandler) seed proteins was prepared by incubation with three different proteases, including pancreatic chymotrypsin and trypsin, and a microbial enzyme proteinase K. The hydrolysates were found to possess excellent antioxidant capacities. The peptide fractions scavenged the 2, 2'-anizo-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) free radicals and inhibited the activity of reactive oxygen species. Walnut protein hydrolysates were also tested, for the first time, against the viability of human breast (MDA-MB231) and colon (HT-29) cancer cell lines. MTT, [3-(4, 5dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide], assay was used to assess in vitro cancer cell viability upon treatment with the peptide fractions. The peptide fractions showed cell growth inhibition of 63 ± 1.73 % for breast cancer and 51 ± 1.45 % for colon cancer cells. Thus, a direct correlation between antioxidant and anticancer activities of walnut peptide fractions exists and supports their potential therapeutic benefit.

Association of ABO blood types with the risk of in-stent restenosis.

OBJECTIVES: To investigate the prevalence of in-stent restenosis (ISR) in patients with various ABO blood types. METHODS: Clinical information from 150 patients with a confirmed diagnosis of ISR and 150 patients with a diagnosis of patent coronary stents in the secondary angiography was collected. Comprehensive demographic and laboratory data, including ABO and Rhesus blood groups, as well as comorbid conditions and vessel and stent characteristics, were recorded for each patient. The association of ABO blood groups with the risk of ISR before and after controlling for coronary risk factors was determined. Categorical data were analyzed with the Chi-square test and numerical values were analyzed with t-tests. Binary logistic regression models were constructed to compare type A and non-A for the frequency of risk factors. RESULTS: A total of 392 stents were implanted in 300 patients. Two hundred and fourteen stents (54.6%) were patent and 178 stents (45.4%) were stenosed. Blood group A was significantly more common in the ISR group (43.3% vs. 28.7%, p=0.03). However, the frequencies of other blood types, as well as Rh antigen, were similar between the two groups. Triglyceride and low-density lipoproteins were the only significantly different variables (221 ± 198 mg/dL vs. 138 ± 76 mg/dL, p<0.001 and 108 ± 36 mg/dL vs. 96 ± 73 mg/dL, p=0.04, in type-A vs. non-A, respectively). After matching for coronary risk factors, there was no difference between A blood type patients and their controls. CONCLUSION: ISR is significantly more prevalent in individuals with the type A blood group. However, this higher association is most likely due to higher atherogenic conditions in patients within this population.

A candidate prostate cancer susceptibility gene at chromosome 17p.

It is difficult to identify genes that predispose to prostate cancer due to late age at diagnosis, presence of phenocopies within high-risk pedigrees and genetic complexity. A genome-wide scan of large, high-risk pedigrees from Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined interval, identifying a gene, ELAC2, harboring mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent hydrolase domain that is conserved among eukaryotes, archaebacteria and eubacteria. The gene product bears amino acid sequence similarity to two better understood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73).

Enoxaparin for the treatment of recurrent aphthous stomatitis: a pilot exploratory clinical trial.

AIM: Low molecular weight derivatives of heparin have been recently suggested for the treatment of different diseases including oral lichen planus (OLP) due to their effectiveness and limited side effects. However, no studies have concerned the effectiveness of these agents in the treatment of recurrent aphthous stomatitis (RAS). The present study then aimed to assess this effectiveness in vivo. METHODS: Included were 30 RAS patients consecutively referred to our centers without any systemic diseases. The ulcers were examined in terms of size and number. Recurrence intervals were recorded by the patients. 1 U/0.002 mL enoxaparin was injected subcutaneously (3 mg). Injections were repeated once a week for 8 weeks. The patients were followed monthly for three months. To determine the level of pain, Visual Analogue Scale (VAS) from 0 to 10 was used. The data were statistically analyzed to determine the difference between the number, size, and pain using Wilcoxon test. RESULTS: It was shown that 8-stage injection of enoxaparin is associated with significantly reduced number, size, recurrence intervals, and the intensity and duration of pain of the lesions in 21 males (70%) and 9 females (30%) of the present study. CONCLUSION: According to the limitations of the present study, systemic Enoxaparin seems successful in reducing the number, size, recurrence frequency and the duration of pain and discomfort in RAS patients without significant side effects.

Porous Silica as Drug Carrier for Controlled Delivery of Sulfasalazine: The Effect of Alginate-N, O-Carboxymethyl Chitosan Gel Coating and Amine Functionalization.

The necessity of colon-specific drug delivery systems has been well recognized. Porous silica (PSi) coated with a pH-sensitive, biocompatible, and biodegradable polymer can be useful in colon delivery. In this study, porous silica was synthesized and sulfasalazine was loaded into it to investigate the release rate in a simulated intestinal media. The media was kept at 37 °C and pH 6.8 and 7.4, and subjected to continuous ultrasonic waves to simulate body fluid flow. Aqueous alginate and N, O-Carboxymethyl chitosan (NOCC) solutions, with a distinct composition (3% W/V) in different ratios, were prepared and coated on pressed porous silica disks. Porous silica (PSi) was also functionalized by aminopropyltrimethoxysilane grafting and was studied as a potential carrier for the controlled drug release of sulfasalazine. The release was studied in simulated gastric and intestinal media and results show that no burst release occurred in both coated and functionalized samples and the swelling degree of coats at basic and neutral media decreased by the presence of alginate in the network. It is concluded that the coat with a 50:50 ratio can release the colon drugs in 24 h at a suitable rate. It is also envisioned that functionalization was a factor boosting drug uptake, however, the release rate was lower in the functionalized samples. This study opens the gates to new ideas for the potential safe and localized delivery of sulfasalazine.

Direct short-term cytotoxic effects of BIBR 1532 on acute promyelocytic leukemia cells through induction of p21 coupled with downregulation of c-Myc and hTERT transcription.

Acute promyelocytic leukemia (APL) is characterized by specific t(15;17), distinct morphologic picture, and clinical coagulopathy that contribute to the morbidity and mortality of the disease. This study aims to investigate the effects of antitelomerase compound BIBR1532 on APL cells (NB4). BIBR 1532 exerts a direct short-term growth suppressive effect in a concentration-dependent manner probably through downregulation of c-Myc and hTERT expression. Our results also suggest that induction of p21 and subsequent disturbance of Bax/Bcl-2 balanced ratio as well as decreased telomerase activity may be rational mechanisms for the potent/direct short-term cytotoxicity of high doses of BIBR1532 against NB4 cells.

First-trimester screening for chromosomal abnormalities by integrated application of nuchal translucency, nasal bone, tricuspid regurgitation and ductus venosus flow combined with maternal serum free ß-hCG and PAPP-A: a 5-year prospective study.

OBJECTIVE: To investigate the performance of first-trimester screening for chromosomal abnormalities by integrated application of nuchal translucency thickness (NT), nasal bone (NB), tricuspid regurgitation (TR) and ductus venosus (DV) flow combined with maternal serum free ß-human chorionic gonadotropin (fß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at a one-stop clinic for assessment of risk (OSCAR). METHODS: In total, 13,706 fetuses in 13,437 pregnancies were screened for chromosomal abnormalities during a period of 5 years. Maternal serum biochemical markers and maternal age were evaluated in combination with NT, NT + NB, NT + NB + TR, and NT + NB + TR + DV flow data in 8581, 242, 236 and 4647 fetuses, respectively. RESULTS: In total, 51 chromosomal abnormalities were identified in the study population, including 33 cases of trisomy 21, eight of trisomy 18, six of sex chromosome abnormality, one of triploidy and three of other unbalanced abnormalities. The detection rate and false-positive rate (FPR) for trisomy 21 were 93.8% and 4.84%, respectively, using biochemical markers and NT, and 100% and 3.4%, respectively, using biochemical markers, NT, NB, TR and DV flow. CONCLUSION: While risk assessment using combined biochemical markers and NT measurement has an acceptable screening performance, it can be improved by the integrated evaluation of secondary ultrasound markers of NB, TR and DV flow. This enhanced approach would decrease the FPR from 4.8 % to 3.4 %, leading to a lower number of unnecessary invasive diagnostic tests and subsequent complications, while maintaining the maximum level of detection rate. Pre- and post-test genetic counseling is of paramount importance in either approach.

The influence of the HLA-DRB1 and HLA-DQB1 allele heterogeneity on disease risk and severity in Iranian patients with multiple sclerosis.

Multiple sclerosis (MS) is a common autoimmune disorder of the central nervous system. Recent studies have shown that the HLA-DRB1 and DQB1 alleles are associated with MS susceptibility and severity. However, this is controversial in different population studies. In the present study, the roles of HLA-DRB1 and DQB1 alleles and the amino acids were investigated on disease risk and severity in 120 Iranian patients with MS and 120 controls. Our findings indicate that the DRB1*1501 allele (OR = 3.203 P = 0.001), the DRB1*1501-DQB1*0602 haplotype (OR = 7.792 P = 0.003) and the DRB1*1501/0701- genotype (OR = 3.320 P = 0.006) and amino acid Leu26 (OR = 1.645 P = 0.005) and Phe9 (OR = 1.893 P = 0.009) on the DQß1 chain are significantly associated with MS susceptibility. DRB1*1001 was the only allele that had a protective effect against MS (P = 0.0004). We also found that the DQB1*0303 allele was significantly associated with disease severity (mean Multiple Sclerosis Severity Score difference = 1.979, P = 0.002). However, protective effect of the DRB1*1001 against MS and also association of DQB1*0303 allele with MS severity need to be confirmed by larger sample size.

The expression of p38, ERK1 and Bax proteins has increased during the treatment of newly diagnosed acute promyelocytic leukemia with arsenic trioxide.

BACKGROUND: Promising reports exist regarding the use of arsenic trioxide (ATO) as first-line treatment in acute promyelocytic leukemia (APL). Although the in vitro effect of ATO is extensively studied, the in vivo mechanism(s) of ATO action is mostly unknown. PATIENTS AND METHODS: Newly diagnosed APL patients were involved and received ATO (0.15 mg.kg/day) for 28 days as induction followed by consolidation therapy. Bone marrow (BM) aspirates were obtained on days 0, 14 and 28 of treatment for further molecular studies. Clinical findings and white blood cell counts were recorded as well. RESULTS: Complete remission was observed in 17 (85%) patients with the median duration of 28 days (18-38) and cumulative dosage of median 280 mg (180-350). Hyperleukocytosis and APL differentiation syndrome (63%), gastrointestinal disorders (30%), liver enzyme elevation and night sweating (50%) were the most prevalent side-effects. The expression of Bax, ERK1 and p38 proteins and caspase-3 activity increased significantly in promyelocytes of BM aspirates at days 14 and 28 of induction therapy. CONCLUSION(S): These findings point toward the role of p38 and Bax in the induction of apoptosis, which was confirmed by increase in caspase-3 activity. However, the increase in ERK1 expression with regard to leukocytosis could translate to a proliferative/differentiation effect.

Trialling diagnosis-related groups classification in the Iranian health system: a case study examining the feasibility of introducing casemix.

This paper examines the quality of routinely collected information in an Iranian hospital in a trial of casemix classification. Australian Refined Diagnosis Related Groups (AR-DRG) were used to classify patient episodes. There were 327 DRGs identified, of which 20% had only 1 case. The grouper program identified invalid records for 4% of total separations. Approximately 4.5% of cases were classified into error DRGs and 3.4% were ungroupable. No complication and comorbidity effects were identified with 93% of total cases. R2 (variance in length of stay explained) was 44% for untrimmed cases, increasing to 63%, 57% and 58% after trimming by L3H3, IQR and 10th-95th percentile methods respectively.

Telomerase activity and telomere length in patients with acute promyelocytic leukemia: indicative of proliferative activity, disease progression, and overall survival.

BACKGROUND: The progressive shortening of telomeres and the activation of telomerase have been considered to be one of the key mechanisms in cellular immortalization and tumor progression. PATIENTS AND METHODS: About 300 sequential samples were collected from 40 patients during the course of acute promyelocytic leukemia (APL) disease. Telomerase activity (TA) and terminal restriction fragment (TRF) length were assessed by TRAP and Southern blot analyses, respectively. PML-retinoic acid receptor alpha (RARa)/glucose-6-phosphate dehydrogenase transcripts were quantified by real-time PCR. RESULTS: About 90% of the patients had a significant reduction in telomere length (TL) relative to the control (median 3.5 versus 11.37 kbp; P < 0.001). A significant positive correlation between TL and PML-RARa expression was found (P = 0.001). Telomerase was activated in all patients; however, TA level was significantly higher in the group of relapsed patients than patient with newly diagnosed. The group of patients with shortened TRF and elevated TA had a significantly poorer overall survival. CONCLUSIONS: The shortened TL and elevated TA in APL patients are mainly indicative of extensive proliferative activity and they correlate with disease progression and relapse; thus, they may serve as prognostic factors for a subset of APL patients with more aggressive disease and poor outcome, those who may not respond favorably to arsenic therapy.

Casemix in the Islamic Republic of Iran: current knowledge and attitudes of health care staff.

Casemix is a tool that classifies patients according to their clinical similarity and the homogeneity of resources required. A descriptive study was conducted to assess the level of knowledge and attitude toward the casemix-based funding system among staff working in the Iranian Social Security Organization in Tehran. The survey showed that knowledge of casemix and diagnosis-related groups (DRG) was poor among the study group and any attempt to implement the casemix system--which about three-quarters of high-level staff had never heard of--would be likely to fail. This highlights the necessity for creating awareness of the casemix and DRG systems among the hospital staff before any action takes place.

Seroprevalence and molecular detection of Toxoplasma gondii in young healthy blood donors in Northern Iran.

T. gondii is a life-threatening infection in immunocompromised patients which may be transmitted through blood transfusion. The present study aimed to evaluate the seroprevalence and molecular detection of T. gondii infection and the associated risk factors among young healthy blood donors in the central part of Mazandaran province, northern Iran. Blood samples were taken from 500 participants and the serum was separated. All serum samples were tested for the presence of anti-T. gondii antibodies (IgG) and then all positive samples were evaluated for IgM antibodies using commercial ELISA kits. All IgM positive samples and 66 randomly selected IgG positive samples were further tested by PCR of the REP-529 gene. Anti-Toxoplasma antibodies (IgG) avidity test was performed for 142 IgG positive samples which were randomly selected. In the current study, anti-T. gondii antibodies (IgG) and (IgM) were found in 316 (63.2%) and 3 (0.95 %) participants, respectively. Seropositivity rate of Toxoplasma was higher among blood donors living in rural areas (P=0.000) and those with a history of soil and animal contact (P<0.05). PCR of the REP-529 gene showed T. gondii DNA in 21 out of 66 samples. The REP-529 gene was not detected in IgM positive samples. Low avidity antibodies (IgG) was found in 23.2% of the IgG positive samples. In conclusions, this study found that the prevalence of toxoplasmosis among young healthy blood donors in north of Iran was high. To reduce the risk of parasite transmission, leukofilteration method are recommended for donated blood used for immunosuppressed patients.

Fludarabine and busulfan as a myeloablative conditioning regimen for allogeneic stem cell transplantation in high- and standard-risk leukemic patients.

Busulfan and cyclophosphamide (BuCy) are currently the most widely used myeloablative regimen to treat malignancies with allogeneic stem cell transplantation. Fludarabine has considerable efficacy in both immunosuppression and tumor cells killing with a minimal extramedullary toxicity. We evaluated the efficacy of 40 mg/m(2) fludarabine i.v. for 5 days and busulfan 4 mg/kg/day p.o. for 4 days as myeloablative conditioning regimen in 70 patients (median age 24 years) with acute leukemia or chronic phase of myelogenous leukemia. They all had human leukocyte antigen-matched sibling donors. The patients received 10 mug/kg granulocyte colony stimulating factor (GCSF), 24 h after stem cell infusion until engraftment occurred. Graft-versus-host disease (GVHD) prophylaxis included 3 mg/kg cyclosporine-A i.v. from day -2 to +6 followed by 12 mg/kg p.o. until day +60. The median time of neutrophil recovery (>0.5 x 109/l) and platelet recovery (>20 x 109/l) were 10 and 12 days, respectively. Mucositis (93%) and hepatic toxicity (16%) resolved with conservative therapy. The incidence of acute GVHD grade I-II and III-IV were 38.6 and 15.7% respectively. Overall survival and disease-free survival were 71 and 64% respectively with 17 months median follow-up for surviving patients. We conclude that FluBu may be used as a substitute for BuCy with almost the same efficacy and with a lower transplant adverse effect but to increase anti-leukemic effects, especially in acute lymphoblastic leukemia patients, it needs some modifications.