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.

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.

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.

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.).

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.

Endoscopic anterior component separation: a novel technical approach.

PURPOSE: Open anterior release of the external oblique fascia to enable midline closure of large abdominal wall defects is associated with relevant morbidity due to extensive subcutaneous dissection. Using endoscopic techniques, wound complications can be minimized. However, identification of the correct entry point (e.g. for balloon trocar insertion) can be challenging especially in adipose patients. We therefore present a technical modification facilitating the entire procedure. METHODS: A novel technique for endoscopic anterior component separation using a trocar system allowing blunt and sharp dissection under direct vision is described. This brief communication also contains our initial experience and learning curve with this novel approach. RESULTS: Endoscopic release of the external oblique fascia was successfully performed 29 times in a total of 15 patients. Body mass index accounted for 30.8 kg/m2 (median; range 21.6-42.5). Transverse width of midline defect accounted for 7 cm (median; range 4-12). Subsequent hernia repair was successfully done using sublay mesh reinforcement (n = 13) or a laparoscopic intraperitoneal onlay mesh procedure (n = 2) with midline closure in all cases. One hematoma was seen at site of release managed conservatively. CONCLUSIONS: Using a trocar system allowing blunt and sharp dissection under direct vision may be a viable option for the endoscopic anterior component separation.

Al2O3-Ti functionally graded material prepared by spark plasma sintering for orthopaedic applications.

Orthopaedic prostheses still suffer from limited lifetime which imposes revision surgery with the associated risks involved. This, to some extent, is related to the vulnerability of the biomaterials used for their fabrication that are commonly single-constituent and uniform. Therefore, hybrid biomaterials such as composites and functionally graded materials (FGMs) are being developed to overcome the shortcomings of available biomaterials. The present paper focuses on the study of the structural, physical and mechanical properties of a FGM made of alumina-titanium fabricated by spark plasma sintering (SPS). The corresponding composites of the individual FGM layer were also fabricated. After sintering, the structural, mechanical and physical tests were carried out. The microstructural analysis using X-ray diffraction revealed the presence of Ti3Al and TiAl in the composites, particularly with the increase of titanium content. Scanning electron micrographs revealed good adhesion and bonding between the two phases and between the FGM layers. The hardness and bending strength of the composites and FGM samples were tested and it was found that the increase in amount of Ti volume fraction decreases these properties monotonically. Furthermore, the sintering behaviour and fracture mechanisms of the FGM sample were studied and discussed.

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.

Tacrolimus Dose Requirement in Iranian Kidney Transplant Recipients within the First Three Weeks after Transplantation.

BACKGROUND: Tacrolimus is the main immunosuppressive agent in many kidney transplant protocols with an initial recommended daily dose of 0.2 mg/kg of ideal body weight (IBW). However, due to the high inter- and intra-patient variability in its pharmacokinetics, the required tacrolimus doses may differ markedly from patient to patient. OBJECTIVE: To assess the required tacrolimus dose to achieve the desired whole blood concentration within the first three weeks after kidney transplantation among Iranian patients. METHODS: This cross-sectional study was performed at kidney transplantation ward of Imam Khomeini Hospital Complex where almost all patients receive thymoglobulin induction therapy and a calcineurin inhibitor, mainly tacrolimus, plus mycophenolate, and prednisolone as maintenance immnosuppressive drugs with the target tacrolimus whole blood concentration of 8-12 ng/mL for the first month after transplantation. RESULTS: The mean±SD administered daily dose of tacrolimus during the first three weeks after transplantation was 0.085±0.024 mg/kg of IBW that resulted in a mean±SD whole blood concentration of 10.34±5.44 ng/mL. The required mean±SD dose of the drug to achieve the desired whole blood level of 8-10 ng/mL was 0.08±0.02 mg/kg. Only 27.4% of the assessed tacrolimus blood levels were within the desired range. Compared with males, females needed 19% more daily dose of tacrolimus to reach similar whole blood levels. Tacrolimus blood levels were significantly correlated with daily tacrolimus doses (r=0.307, p=0.001) and patients' age (r=0.283, p=0.003). CONCLUSION: It seems that Iranian kidney transplant recipients need lower daily doses of tacrolimus to achieve the desired whole blood levels; compared with males, females need a higher dose.

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.

Lithium attenuated the depressant and anxiogenic effect of juvenile social stress through mitigating the negative impact of interlukin-1ß and nitric oxide on hypothalamic-pituitary-adrenal axis function.

The neuroimmune-endocrine dysfunction has been accepted as one of fundamental mechanisms contributing to the pathophysiology of psychiatric disorders including depression and anxiety. In this study, we aimed to evaluate the involvement of hypothalamic-pituitary-adrenal (HPA) axis, interleukin-1ß, and nitrergic system in mediating the negative behavioral impacts of juvenile social isolation stress (SIS) in male mice. We also investigated the possible protective effects of lithium on behavioral and neurochemical changes in socially isolated animals. Results showed that experiencing 4-weeks of juvenile SIS provoked depressive and anxiety-like behaviors that were associated with hyper responsiveness of HPA axis, upregulation of interleukin-1ß, and nitric oxide (NO) overproduction in the pre-frontal cortex and hippocampus. Administration of lithium (10 mg/kg) significantly attenuated the depressant and anxiogenic effects of SIS in behavioral tests. Lithium also restored the negative effects of SIS on cortical and hippocampal interleukin-1ß and NO as well as HPA axis deregulation. Unlike the neutralizing effects of l-arginine (NO precursor), administration of l-NAME (3 mg/kg) and aminoguanidine (20 mg/kg) potentiated the positive effects of lithium on the behavioral and neurochemical profile of isolated mice. In conclusion, our results revealed that juvenile SIS-induced behavioral deficits are associated with abnormalities in HPA-immune function. Also, we suggest that alleviating effects of lithium on behavioral profile of isolated mice may be partly mediated by mitigating the negative impact of NO on HPA-immune function.

Expression analysis of microRNA-125 in patients with polycythemia vera and essential thrombocythemia and correlation with JAK2 allele burden and laboratory findings.

INTRODUCTION: The JAK2V617F mutation has emerged in recent years as a diagnostic as well as a treatment target in patients with polycythemia vera (PV) and essential thrombocythemia (ET). The disease phenotype is also influenced by other factors such as microRNA (miRNA) deregulation. The aim of this study was to investigate miR-125 expression level in these patients with those obtained from healthy control subjects and its correlation with JAK2 allele burden and laboratory findings. METHODS: In total, forty patients with a clinical diagnosis of PV and ET were examined at the time of diagnosis. Ten healthy subjects were checked as controls. We performed JAK2 V617F allele burdens measurement and expression analysis of miR-125b-5p, miR-125b-3p, miR-125a-5p, and miR-125a-3p in leukocytes isolated from peripheral blood by quantitative real-time polymerase chain reaction. RESULTS: MiR-125b-5p and miR-125a-5p were upregulated in both patients with PV (P = 0.00 and P = 0.003, respectively) and ET (P = 0.02 and P = 0.002, respectively). In PV group, a significant correlation was observed between miR-125a-5p and platelet counts (P = 0.01, r = 0.531). The correlation between miRNA and JAk2 allele burden was not significant. CONCLUSION: In conclusion, our data indicate that other factors such as aberrant miR-125 expression may influence on the disease phenotype in patients with PV and ET.

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.

Apigenin modulates the expression levels of pro-inflammatory mediators to reduce the human insulin amyloid-induced oxidant damages in SK-N-MC cells.

Amyloid depositions of proteins play crucial roles in a wide variety of degenerative disorders called amyloidosis. Although the exact mechanisms involved in amyloid-mediated cytotoxicity remain unknown, increased formation of reactive oxygen species (ROS) and nitrogen species and overproduction of pro-inflammatory cytokines are believed to play key roles in the process. In that regard, we investigated the effect of apigenin, a common dietary flavonoid with high antioxidant and anti-inflammatory properties on potential factors involved in cytotoxicity of human insulin amyloids. Pretreatment of SK-N-MC neuroblastoma cells with apigenin increased cell viability and reduced the apoptosis induced by insulin fibrils. In addition, apigenin attenuated insulin fibril-induced ROS production and lipid peroxidation. Our result also demonstrated that pretreatment of the fibril-affected cells with apigenin caused an increase in catalase activity and the intracellular glutathione content along with reduction in nitric oxide production and nuclear factor κB, tumor necrosis factor α, and interleukin 6 gene expression based on real-time polymerase chain reaction evaluation. In accordance with these results, apigenin could be a promising candidate in the design of natural-based drugs for treatment or prevention of amyloid-related disorders.

Comparison of pectoral angina misconception among Iranian nurses, nursing students and patients.

Background and objective: previous studies revealed some angina misconception among patients and health care providers. The aim of this study was to assess the misconceptions about angina held by nurses, nursing students and patients. Materials and methods: In this cross sectional study, 120 nurses, 120 nursing students, and 120 patients with angina pectoris in Iran participated. Data were gathered by using the York angina belief Questionnaire version 1. The mean of angina misconception were compared by using ANOVA analysis of variance. The correlations between the questionnaire and the variables were calculated by regression. α < 0.05 was considered significant. Results: Nursing students had a significantly lower misconception than patients and nurses (39.03 ± 6.35 vs. 43.70 ± 7.22 in nurses and 43.78 ± 5.77 in patients, P = 0.001). However, the differences between nurses and patients with angina, regarding the misconception score, were not significant: 43.70 ± 7.22 vs. 43.78 ± 5.77, P = 0.9, and no statically significant association was made between age, sex, education, training and number of misconception in patients, nurses and nursing students. Conclusion: Nurses have the most pregnant relationship with patients at different stages of their treatment and can play an important role in assessing their misconceptions and intervention to dispel them. It seems that the nursing students and the nurses' continual professional educations should be emphasized to use the scientific knowledge to dispel the misconceptions in patients.

A retrospective evaluation of doxorubicin-based chemotherapy for dogs with right atrial masses and pericardial effusion.

OBJECTIVE: To report the outcome of doxorubicin-based chemotherapy as the sole treatment for dogs with echocardiographically identified right atrial masses and pericardial effusion. METHODS: A retrospective study of case records of dogs with right atrial masses treated with doxorubicin. Dogs were excluded from the study if they had any type of surgery performed such as pericardiectomy or right atrial mass resection, or if their chemotherapy protocol did not include doxorubicin. The data collected included signalment, history, physical examination findings, diagnostic test results and long-term survival. RESULTS: Dogs with right atrial masses and pericardial effusion that received doxorubicin-based chemotherapy alone had a median survival of 139 · 5 days (range 2 to 302 days). Chemotherapy side effects were frequent but mild. CLINICAL SIGNIFICANCE: Doxorubicin-based chemotherapy alone appears to be a viable treatment option for dogs with echocardiographically identified right atrial masses and pericardial effusion.