Ahmadreza Dehpour, PharmD, PhD
Vol 55, No 9 (2017)
Matrix metalloproteinase-9 (GELB) as a member of gelatinases plays key role in the destruction of blood-brain barrier (BBB), T cells migration into the CNS, and demyelination induction. Considering remyelination induction in response to tart cherry extract and pure p-coumaric acid ingestion via tracking MMP9 gene expression in the cuprizone mouse model. Firstly, predicting the chemical interaction between p-coumaric acid and MMP9 protein was conducted through PASS and Swiss dock web services. Next, the content of p-coumaric acid in the tart cherry extract was analyzed by HPLC. Later, mice (male, female) were categorized into two groups: standard, cuprizone. After the demyelination period, mice classified into four groups: standard, natural chow, tart cherry extract, p-coumaric acid. Finally, brains were extracted from the skull, and MMP9 gene expression was evaluated by real time RT-PCR. Bioinformatics analysis displayed p-coumaric acid has potent inhibitory effect on MMP9 gene expression (Pa=0.818) with estimated ΔG (kcal/mol) -8.10. In addition, during the demyelination period, MMP9 expression was increased significantly in the male group that is related to myelin destruction. However, MMP9 was declined throughout remyelination in both male and female. It’s remarkable that pure p-coumaric acid and tart cherry extract ingestion could decrease the gene expression ratio more than natural chow. According to the results, it’s deduced the male mouse is more appropriate gender for demyelination induction via cuprizone. In addition, tart cherry extract and pure p-coumaric acid ingestion could decrease MMP9 gene expression level considerably during remyelination.
Minichromosome maintenance complex component 6 (MCM-6) is one of the six proteins of the MCM family, which are involved in the initiation of DNA replication, represents a marker of proliferating cells. The goal of this study was to evaluate the prognostic relevance of the neoplastic cell proliferation rate in patients with Hodgkin's lymphoma (HL). We evaluated the formalin-fixed paraffin-embedded lymph node biopsy specimens from 55 patients by using monoclonal antibody against MCM-6 and compared these findings with clinical data and treatment outcome. Median of MCM-6 expression was 85% (range: 35%-99%). In multivariate analysis, MCM-6 expression, B symptoms, and age were not statistically significant predictor for relapse in contrary to response (P=.001) and stage of disease (P=.048). Patients with lower MCM-6 expression rates showed higher relapse rate and lower disease-free survival (DFS). Meanwhile, patients with MCM-6 expression less than 85% showed shorter DFS (P=.031). We hypothesize that in group of patients with lower MCM-6 expression rate, a larger proportion of proliferating malignant cells are arrested in the very early phase of mitosis, in comparison to the group of patients with higher MCM-6 expression, and this could imply a shorter and probably higher relapse rate in the former group.
This sub-analysis of the Iran-AFECT study was to determine the baseline characteristics are predicting the likelihood of attainment of HbA1c goal and changing in HbA1c after initiation of basal insulin glargine in insulin naïve people with type 2 diabetes not adequately controlled with oral glucose-lowering drugs. Iran-AFECT was a 24-week, prospective, multicenter, observational study of people with type 2 diabetes initiated or switched to insulin glargine. In this sub-analysis, we included all insulin naïve people. Glycemic response was defined as HbA1c≤7.0% and/or change in HbA1c at week 24. Data on 433 participants were included. The mean HbA1c was 8.9%±0.9% at baseline which decreased to 7.6%±1.2% (P<0.001). By week 24, 36% of the participants reached HbA1c≤7.0%. In univariate analysis, the strongest association was for the baseline HbA1c (r2=0.32, P<0.001). In multivariate analysis, predictors of change in HbA1c were baseline HbA1c (r2=0.29, P<0.001), and dosing of glargine (r2=0.01, P=0.02). The baseline HbA1c was accounting for 88% of explainable variances in HbA1c. The best cut-off predicting glycemic response for baseline HbA1c was 8.5%. Among factors predicting response to initiating basal insulin therapy with insulin glargine, baseline HbA1c is the strongest predictor explaining most of the variances in HbA1c change.
Due to a close link between cardiovascular disorders and increased acute phase responses, it is now proposed the relation of total sialic acid (TSA) and C Reactive Protein (CRP) as main components of acute phase proteins and cardiovascular risk profiles such as diabetes mellitus and smoking. We hypothesized that the elevation in the level of TSA along with other prototype acute phase reactants such as CRP is expected more in the coexistence of diabetes and smoking than in diabetes mellitus alone. Ninety diabetic patients were randomly selected and entered into this case-control study. Using block randomization method, the patients were randomly assigned into smokers (n=45) and nonsmokers (n=45). A group of ten healthy individuals was also included as the control. The serum levels of TSA, CRP, iron, and hemoglobin were measured by the specific techniques. Comparing laboratory parameters across the three groups indicated significantly higher levels of TSA and CRP in smoker diabetics as compared to non-smoker diabetics and the healthy controls, while there was no difference in other parameters including serum iron and hemoglobin. A significant positive correlation was also revealed between TCA and CRP (r=0.324, P=0.030), but no significant association was found between other parameters. In the background of smoking, increasing the level of both TSA and CRP is predicted more than the existence of diabetes mellitus alone. In fact, the increase in these biomarkers is more predictable in smoker than in nonsmoker diabetics. This finding emphasizes the increased risk for cardiovascular disorders in smoker compared to non-smoker diabetics.
It is very important to have proper management in children with Seizure. Electroencephalography (EEG) as a diagnostic instrument has a key role in determining the management method of seizure in children. Because of poor cooperation of some children (especially children with attention deficit hyperactivity disorders and developmental disorders) in performing EEG, it is the best choice to sedate children before EEG. The aim of present study is to evaluate the sedation efficacy of clonidine in children before EEG. In a randomized clinical trial, 45 children age 2 to 12 with seizure, who referred to Children Hospital of Tabriz University of Medical Sciences and candidate for EEG, were studied. Sedation before EEG induced by 0.5 to 2.0 mg clonidine orally. Sedation score (0 to 5) measured by using eyes condition, response to voice, and response to touch. Successful sedation, EEG performing, and hemodynamic stability were evaluated during sedation. Of all patients, 40 patients (88.88%) were sedated successfully, and EEG was performed for all of the children. Mean onset time of clonidine effect was 35.47±13.56 minutes and mean time of that the patients’ level of consciousness back to the level before administrating of clonidine was 77.55±26.87 minutes. Hemodynamic states of all patients were stable during the study, and there were no significant changes in vital sign of patients. In conclusion, clonidine can be considered as a safe alternative medication for sedation for EEG, which is fortunately associated with no significant change in vital signs, which may complicate overall status of patients.
Patellar instability is a multifactorial common knee pathology that has a high recurrence rate, and the symptoms continue and ultimately predispose the patient to chondromalacia and osteoarthritis. Tibial tuberosity-trochlear groove distance (TTTG) is very important in the assessment of patellofemoral joint instability. The purpose of this study was to report the normal value of TTTG in males and females in different age groups and to assess the reliability of MRI in measuring TTTG. All patients presenting with knee pain and normal examinations of the knee joint, with a normal MRI report, referring to Shahid Sadoughi hospital of Yazd, Iran, from April 2014 to September 2014, were included in the study. MR images were studied once by two radiologists and for the second time by one radiologist. Mean value of TTTG was reported for males and females and in three age groups. Intra- and inter-observer reliability was calculated. A total of 98 patients were eligible to evaluate during 6 months (68 male and 30 female). Mean TTTG was 10.9±2.5 mm in total, which was 10.8±2.8 mm and 11.3±2.3 mm in males and females, respectively (P>0.05). Mean TTTG in males ≤30 years, 30-50 years and, ≥51-year-old were 10.8±2.6 mm, 10.8±2.7 mm, and 10.8±2.6 mm, respectively; that was 12.1±3.4 mm, 11.4±1.9 mm, and 10.5±1.7 mm in females ≤30 years, 31-50 years and, ≥51-year-old, respectively (95% CI). The coefficient of variation was <10% for both intra- and interobserver analysis. The results of the present study showed no significant difference in TTTG value between males and females in different age groups. In addition, it demonstrated that MRI is a reliable method in assessment of TTTG and identified normal value for TTTG at 10.9±2.5 mm.
Given the ongoing controversy over the risks and benefits of on-pump versus off-pump coronary artery bypass graft surgery (CABG), we aimed to compare time trends in off- and on-pump CABG long-term outcomes. In this prospective cohort study, the patients who underwent primary isolated non-emergent CABG in Imam Reza Hospital in Mashhad, Iran, in 2006 were followed for 6 years. The patients were contacted to obtain long-term follow-up data such as death, rehospitalization, myocardial infarction, and normal physical activity. The obtained data were analyzed in SPSS software (V: 16) using t-test, Fisher's Exact, chi-square, and Mann-Whitney tests, and relative risk. The significant level was set at P<0.05.The study included 61 patients of whom n=40 (65.6%) underwent off-pump CABG. The mean age of the patients was 59.0±11.31 years, and n=43 (70.5%) were men. No significant differences were found between the two groups in terms of outcomes during the 6 years (e.g., death, rehospitalization, myocardial infarction, and normal physical activity). There was 1 (5.0%) death, overall. Risk-adjusted death did not differ significantly between the off-pump and on-pump groups during the 6 years (RR, 0.952; 95% CI 0.866 to 1.048).According to the results, the outcomes were similar between off-pump and on-pump CABG in patients who underwent primary isolated non-emergent CABG during the 6-year follow-up phase.
Mucopolysaccharidosis VI (MPS-VI) is an infrequent autosomal recessive disorder caused by mutations in ARSB gene and deficiency in lysosomal enzyyme ARSB activities subsequently. This enzyme is essential for the breaking of glycosaminoglycans (GAGs) such as dermatan sulfate and chondroitin sulfate. ARSB dysfunction results in imperfect breakdown of GAGs and their accumulation in urine. Mutations in ARSB gene are the main players in MPS-VI disease and its clinical consequences. Most reported mutations are point mutations but there are some other examples in literature. Here we report a novel missense mutation in ARSB gene that is inherited as an autosomal recessive mode and probably explain the clinical status of the proband. This mutation replaces the threonine 92 by proline and alters ARSB structure. This is the most feasible scenario for clinical condition we described here. This novel mutation should be remarked for PND and PGD to improve the health and management of such families.
Extramammary Paget’s disease is an uncommon intraepithelial adenocarcinoma in genital and perianal regions. Genital wart is the most common sexually transmitted disease caused by human papilloma viruses and vulval lichen sclerosus is chronic pruritic dermatitis in genital area which could be able to change to invasive squamous cell carcinoma. We report a patient who had simultaneous lichen sclerosus, genital wart and extramammary Paget’s disease of the vulva. We could not find any significant association between them in literature.
Bowen's disease (BD) is an epidermal in-situ squamous cell carcinoma (SCC). Most Human Papilloma Viruses (HPV)-positive lesions in Bowen's disease are localized to the genital region or distal extremities (periungual sites) in which HPV type-16 is frequently detected. Patient was a 64-year-old construction worker for whom we detected 2 erythematous psoriasiform reticular scaly plaques on peri-umbilical and medial knee. Biopsy established the diagnosis of Bowen's disease and polymerase chain reaction assay showed HPV-6, -18 co-infection. Patient was referred for surgical excision.
We report a patient presented with recurrent pericardial effusion caused by drug-induced systemic lupus Erythematosus (SLE) following mitral valve repair. The surgery was complicated by hemiparesis and convulsion in early postoperative period. The patient had been received carbamazepine for a paroxysmal seizure that occurred following mitral valve repair. The post operative computed tomography showed embolic stroke and its sequel (seizure) that treated with carbamazepine. In the 3rd month of follow-up, however, hemiparesis recovered by physiotherapy but carbamazepine was not discontinued as by request of neurologist. In the 6th month of surgery, the patient admitted by dyspnea and massive pericardial effusion that treated by subxiphoid drainage. This event was re occurred in two times in a short time frame and each event treated by surgical approach. The serologic exam in the last admission revealed drug-induced lupus erythematosus. The carbamazepine as an anti convulsive drug has been described to cause LE like disease in multiple case reports. Laboratory exam exhibited the possibility of carbamazepine-induced lupus in our case, with the extremely rare presentation of recurrent massive pericardial effusion.