In Silico Interactions of Natural and Synthetic Compounds with Key Proteins Involved in Alzheimer's Disease: Prospects for Designing New Therapeutics Compound.

Memory impairment is a result of multiple factors including amyloid-beta (Aß) accumulation. Several receptors are mediated for Aß transport and signaling. Moreover, blood lipids are involved in Aß signaling pathway through these receptors. Mediated blood lipid level by statins aims to regulate Aß signaling cascade. First, the structure of receptors was taken from the RCSB PDB database and prepared with MGLTools and AutoDock tool 4. Second, the ligand was prepared for docking through AutoDock Vina. The binding affinity was calculated, and the binding sites were determined through LigPlot+ software. Besides, pharmacokinetic properties were calculated through multiple software. Finally, a molecular dynamics (MD) simulation was conducted to evaluate ligands stability along with clustering analysis to evaluate proteins connection. Our molecular docking and dynamic analyses revealed silymarin as a potential inhibitor of acetylcholinesterase (AChE), P-glycoprotein, and angiotensin-converting enzyme 2 (ACE2) with 0.704, 0.85, and 0.83 Å for RMSD along with -114.27, -107.44, and -122.51 kcal/mol for free binding energy, respectively. Moreover, rosuvastatin and quercetin have more stability compared to silymarin and donepezil in complex with P-glycoprotein and ACE2, respectively. Eventually, based on clustering and pharmacokinetics analysis, silymarin, rosuvastatin, and quercetin are suggested to be involved in peripheral clearance of Aß. The bioactivity effects of mentioned statins and antioxidants are predicted to be helpful in treating memory impairment in Alzheimer's disease (AD). Nevertheless, mentioned drug effect could be improved by nanoparticles to facilitate penetration of the blood-brain barrier (BBB).

Attitude toward end-of-life care in emergency medicine residents- can a short workshop make a difference?

BACKGROUND: There is a growing demand for palliative care (PC) in Emergency departments (ED) as the number of patients who need end-of-life (EOL) care is increasing. Despite significant variability amongst residency programs, there is a lack of structured core curriculum for PC/EOL care in most emergency medicine (EM) training programs, which often do not meet the needs of EM physicians. In this study, we evaluate the effect of a short EOL care workshop on changing the attitude of Iranian EM residents towards EOL care in ED. METHOD: In this prospective before/after educational study at Tehran University of medical science, we enrolled 40 EM residents using a random sampling method. We obtained demographic and practice background information, and participants underwent a half-day PC training workshop designed by an expert panel. We administered a translated and validated Standard PEAS (physician End of Life Care Attitude Scale) questionnaire before and four weeks after an educational intervention. Baseline and differences in attitude were reported and compared by paired t-test, repeated measure ANOVA, and ANOVA. RESULTS: None of the participants had prior experience of formal PC training. All of the 40 participants completed the follow-up questionnaire. Baseline attitude was not different among demographic groups. The mean (SD) PEAS score before and four weeks after the workshop was 86.9 (5.8) versus 89(6.9), respectively (P = 0.023). Residents with no previous close exposure to a terminal illness in their family members had significantly more attitude change than those with such an experience (P = 0.045). CONCLUSION: A brief educational intervention improved EM residents' attitudes toward EOL care. The optimal design and characteristics of this educational intervention yet remain to be defined by further studies.

Neurochemical Ameliorating of the Hippocampus in Dyslipidemic Alzheimer Patients Following Silymarin; a Double-Blind Placebo-Controlled Randomized Clinical Trial.

Background: Amyloid-beta (Aß) production is a normal physiological process, and an imbalance in Aß production/excretion rate is the basis of the plaque load increase in AD. LRP1 is involved in both central clearance of Aß from the CNS and transport of Aß toward peripheral organs. In this study, the effect of silymarin combination compared to rosuvastatin and placebo on neuro-metabolites and serum levels of LRP1 and Aß1-42 proteins and oxidative stress enzymes and lipid and cognitive tests of Iranian AD patients. Methods: In this double-blind placebo-controlled study, thirty-six mild AD patients were divided into groups (n=12) of silymarin 140mg, placebo, and rosuvastatin 10mg. Medications were administered 3 times a day for 6 months. Clinical tests, lipid profile (TG, HDL, TC, and LDL), Aß1-42, and LRP1 markers were measured at the beginning and end of the intervention. Magnetic resonance spectroscopy (MRS) was used to measure metabolites. Using SPSS software a one-way ANOVA test was used to compare the means of the quantitative variables and Pearson and Spearman's correlations to measure the correlation. GraphPad Prism software was used for drawing graphs. P < 0.05 was considered a significant. Results: The levels of LRP1 and Aß1-42 in the silymarin group were significantly increased compared to the other groups (P < 0.05). NAA/mI in the silymarin group had a significant increase compared to both placebo and rosuvastatin groups (P < 0.05). Right and left hippocampal mI/Cr directly correlated with TG (r = 0.603, P = 0.003 and r = 0.595, P = 0.004, respectively). NAA/Cr of the right and left hippocampus was inversely related to TG (r = -0.511, P = 0.0033, and r = -0.532, P = 0.0021, respectively). NAA/Cr and NAA/mI of bilateral hippocampi directly correlated with HDL (P < 0.05). An inverse correlation was observed between the Aß1-42 and mI/Cr of the right and left hippocampus (r = -0.661, P = 0.000 and r = -0.638, P = 0.000, respectively). Conclusion: Donepezil and silymarin improved lipid profile associated with increased NAA/Cr, and decreased mI/Cr, in AD patients. Biomarker NAA/mI can be clinically significant in examining AD pathology. Measurement of the lipid factors and neurometabolites can be a suitable method for monitoring this disease.

Silk fibroin and Nettle extract promote wound healing in a rat model: A histological and morphometrical study.

INTRODUCTION: Considering the anti-inflammatory, antimicrobial ability, and antioxidant effects besides stimulating ability of silk fibroin (SF) in cell migration and proliferation of Nettle, the current study aimed to investigate the effect of Nettle leaf extract (NLE) and SF on histology, morphometrical parameters and apoptosis on the wound in the rat model. MATERIALS AND METHODS: Wistar rats are divided into 5 groups, including 1-control (rats with healthy skin and no treatment); 2-wound (without any treatment); 3-SF (administration of silk fibroin solution for 14 consecutive days); 4- Nettle (administration of Nettle ointment for 14 consecutive days), and 5- Eucerin group (administration of Eucerin substance for 14 consecutive days) and then assessed wound area by photography, angiogenesis, inflammation, and thickness of epidermis using hematoxylin and eosin (H&E) staining, collagen deposition, and structure of dermis layers evaluated by Masson's trichrome staining and the apoptosis index determined by tunnel assay on days 7, 14 and 21. RESULTS: photographic illustrations showed that the wound surface environment on the seventh day in group 4 was significantly different from group 2 (p < 0.002). The rate of wound healing on the fourteenth day was higher in groups 3 and 4 than in group 2 (p < 0.001). Also, at this time, group 4 was significantly different from group 3 and group 5 (p = 0.003 and p = 0.000, respectively). There was a significant difference in epidermal thickness between the wound group and other experimental groups (p < 0.05). The number of apoptotic cells at the wound edges on the seventh day in both group 3 and group 4 had a significant decrease compared to other groups of wounds (p = 0.000), but there was a significant increase on the fourteenth day. Also, on the 21st day, a significant decrease in apoptotic cells was observed in both group 3 and group 4 compared to other wound groups (p = 0.000). DISCUSSION AND CONCLUSION: Nettle and SF maintain cell homeostasis and accelerate wound closure by reducing cell apoptosis and enhancing cell proliferation on the seventh day, but by increasing the apoptosis of fibroblast cells on the fourteenth day, they lead to remodeling and keratinocytes migration to epidermis formation. Increased apoptosis also seems to be one of the pathophysiological mechanisms to prevent the formation of keloid and hypertrophic scar tissue. SF and Nettle extract, by increasing cell proliferation and migration of different cell types to the site of injury, control the remodeling process by inducing and regulating apoptosis in the first two weeks of wound healing and accelerating the process of collagen deposition and epithelialization.

The cost effectiveness of rotavirus vaccination in Iran.

Rotavirus is the most common cause of severe diarrhea leading to hospitalization or disease-specific death among young children. Effective vaccines have recently been approved and successful vaccination program implemented. The aim of this study was to evaluate the cost effectiveness of mass rotavirus vaccination program in Iran. We developed a Markov model that reflects key features of rotavirus natural history. Parameters of the model were assessed by field study or developed through literature search and published data. We applied the model to the 2009 Iranian birth cohort and evaluated the cost-effectiveness of including the rotavirus vaccine (Rotarix®) into Iranian expanded immunization program (EPI). With an estimated hospitalization rate of 0.05 and outpatient rate of 0.23 cases per person-year, vaccinating cohort of 1231735 infants in Iran with 2 doses of (Rotarix®), would prevent 32092 hospitalizations, 158750 outpatient visits, and 1591 deaths during 5 y of follow-up. Under base-case assumption of $10 cost per course of vaccine, the vaccination would incur an extra cost of $1,019,192 from health care perspective and would avert 54680 DALYs. From societal perspective, there would be $15,192,568 saving for the society with the same averted DALYs. The incremental cost effectiveness ratio showed a cost of $19 US dollars per averted DALY from health care perspective and a saving of $278 US dollars for each averted DALY from societal perspective. Introducing rotavirus vaccine into EPI program would be highly cost-effective public health intervention in Iran.

Controlled Blood Pressure in Iranian Patients: A Multi-Center Report.

We decided to determine the percentage of hypertensive patients whose blood pressure (BP) measurements were within recommended controlled range and to identify predictive factors for controlled BP. In this study carried out in 2014, 280 patients were included consecutively through sampling from both university and private medical centers/pharmacies in four Iranian cities. Demographic data as well as information about duration of HTN and prescribed medications, admission to emergency department (ED) because of HTN crisis, comorbidities, and control of HTN during the last 6 months by a healthcare provider were gathered. Adherence to anti-hypertensives was also determined using the validated Persian version of the 8-item Morisky Medication Adherence Scale (MMAS-8). Controlled BP was defined as systolic BP< 140 and diastolic BP< 90 mmHg in non-diabetics and < 130/80 mmHg in diabetics. Of 280 patients, 122 subjects (43.6%) had controlled BP. Among 55 diabetics, only two patients (3.6%) had controlled BP. Multiple logistic regression revealed the following variables as significant predictors of controlled BP: higher MMAS-8 score (adjusted odds ratio (OR)= 1.19, P= 0.03), fewer number of comorbid conditions (adjusted OR= 0.71, P = 0.03), having occupation as clerk/military personnel (adjusted OR= 1.03, P= 0.04), and not having history of ED admission during the last 6 months because of HTN crisis (adjusted OR= 2.11, P= 0.01). Considerable number of the studied patients had uncontrolled BP. Regarding the dramatic consequences of uncontrolled high BP in long term, it is advisable that careful attention by health care providers to the aforementioned factors could raise the likelihood of achieving controlled BP.

Human papillomavirus detected in esophageal squamous cell carcinoma in Iran.

INTRODUCTION: Considering the different results obtained regarding the association of HPV with the development of esophageal squamous cell carcinoma (ESCC) in different populations, we aimed to determine the frequency of HPV infection and its subtypes in ESCC in Iranian patients. METHOD: A total of 100 paraffin-embedded tissue samples of ESCC diagnosed during 1991 and 2005 in the Institute of Cancer affiliated to Tehran University of Medical Sciences were selected. Seven out of 100 samples were excluded due to low quality of extracted DNA from paraffin-embedded specimens. Thus, 93 samples were included for HPV genotyping. RESULT: All samples were examined using SPF10 primers for HPV detection. HPV DNA was positive in 8 out of 93 (8.6%) ESCC specimens. Using INNO-LiPA genotyping system we detected the genotypes of 5 out of 8 HPV-positive samples. Both HPV types 16 and 6 were detected in 3 specimens; one sample was positive for HPV type 18 and 2 samples were co-infected with two HPV types. There were no statistically significant differences between HPV-positive and HPV-negative cases with regard to clinical and pathologic findings. Three samples were positive for SPF10 indicating HPV infection; however, the exact HPV type could not be clarified using INNO-LiPA genotyping . CONCLUSION: In conclusion, the present study showed that a small proportion of ESCC specimens from Iran harbor HPV16, 18 genome using a highly sensitive method. As different rates have been reported from Iran, a more widespread study with more precise definition of geographical differences could delineate the potential involvement of HPV in the development of ESCC in Iranian population.

Does cosmetic rhinoplasty affect nose function?

Objective. To evaluate the changes in nasal dimensions of healthy Iranian volunteered for cosmetic rhinoplasty after surgery using acoustic rhinometry. Methods. Pre- and postoperative nasal dimension of 36 cases undergoing cosmetic rhinoplasty were compared using acoustic rhinometry (AR), and the measured variables were distance to first and second constriction (d1, d2), first and second minimal cross-sectional area (MCA1, 2), and volume. Results. Mean age (SD) of cases were 24.63 (4.4) years. Septoplasty was performed in 12 cases (33.3%). After surgery, bilateral d1 and both MCA2 decreased significantly, while significant increase was observed in MCA1 postoperatively using decongestant. Cases with septoplasty experienced more increase in MCA1 and less constriction in MCA2 postoperatively. In cases with rhinoplasty alone, they received benefit from double osteotomy in MCA1. In either group of rhinoplasty with and without septoplasty, placing a strut was beneficial for patients. Discussion. The cross-sectional area of the nose is a major factor in the determination of airflow. Cosmetic rhinoplasty may generate a mix effect on nose function. Performing osteotomy may better help patients to save nasal patency, septoplasty is beneficial even in mildly deviated septums, and placing a strut may be beneficial in most of the cases.

Management and outcome of steroid-resistant nephrotic syndrome in children.

INTRODUCTION: Steroid-resistant nephrotic syndrome (SRNS) is uncommon in children, but often leads to ESRD. We report our experience with SRNS and its treatments and outcomes. MATERIALS AND METHODS: We assessed 73 children with SRNS admitted to Ali Asghar Children Hospital in Tehran, Iran. Their clinical presentations, treatment, and disease courses were reviewed. The mean follow-up duration was 6.0 +/- 4.2 years. Moreover, survival times were calculated and the Cox regression method was used to determine variables able to predict survival of the kidneys. RESULTS: Age at the onset of the disease, sex, and hematuria were not predictive of the response to treatment with immunosuppressive drugs in the children with SRNS. The type of resistance (early or late) was associated with the responsiveness to immunosuppressives. Response to any of the immunosuppressive drugs determined the responsiveness to other immunosuppressive drugs. Cyclosporine was more effective than cyclophosphamide as initial therapy. The mean kidney survival time was 11.62 years. Kidney survival rates were 94.6%, 70.0%, 56.0%, and 34.0% at 1, 5, 10, and 15 years, respectively, in patients with initial resistance to steroid, while these were 100%, 100%, 83.0%, and 83.0% in those with late resistance, respectively (P = .03). CONCLUSIONS: We showed that patients with late steroid resistance had better response to immunosuppressive drugs than patients with early resistance. We also showed that resistance to immunosuppressive therapies increased the risk of resistance to other immunosuppressive drugs. Achievement of complete or partial remission with any therapy reduced the risk of ESRD.

Doxycycline plus levamisole: combination treatment for severe nodulocystic acne.

BACKGROUND: Levamisole is an agent without much potential use alone, but through immunomodulation, may synergistically improve the efficacy of other drugs like doxycycline in the treatment of acne vulgaris. OBJECTIVE: The goal of this study was to determine the efficacy of levamisole in addition to doxycycline in the treatment of patients suffering from severe nodulocystic acne. METHODS: A double-blind, randomized, placebo-controlled trial was conducted in the dermatology clinic of Rasoul-e-Akram Hospital in Tehran, Iran in 2006. Sixty patients were randomly assigned to 1 of 2 study groups. The case group was administered oral levamisole 2.5 mg/kg/wk (up to 150 mg/wk) plus doxycycline 100 mg daily and the control group was given 100 mg of oral doxycycline daily and a placebo. Patients were evaluated at baseline, and at 2-month, 4-month, and 6-month checkpoints. RESULTS: The responses to treatment were significantly higher in the case group according to the reduction in total lesions count, acne severity index; and papule/pustule and nodule/cyst count at the 2nd, 3rd, and 4th visits. CONCLUSION: Results indicated that adding oral levamisole to doxycycline is an effective treatment for severe nonresponsiveness to conventional treatments of acne vulgaris. In the patient group, levamisole was well tolerated with an acceptable safety profile. At the time of publication, this study is the first clinical trial that suggests levamisole as an effective new treatment for severe acne vulgaris.

Epidemiologic features, seasonal variations and false positive rate of acute appendicitis in Shahr-e-Rey, Tehran.

INTRODUCTION: Appendicitis is the most common acute surgical condition of the abdomen. Age, sex and seasonal variations have been observed in many studies. To describe and find the possible differences in the epidemiology of acute appendicitis in Shahr-e-Rey, we carried out a retrospective study of all patients with acute appendicitis admitted to Shohadaay-e Haftom-e Tir hospital as it is the only hospital in this restricted part of Tehran. METHODS: Using hospital discharge abstract of patients who were admitted with the diagnosis of acute appendicitis from summer 1996 to spring 2004, we studied the demographic features, particularly age and sex, date of admission and final diagnosis of these patients. RESULTS: During the observation period, 1093 cases were admitted with the diagnosis of acute appendicitis. Of these, 74.4% were males and 6.1% were not actually an acute appendicitis. The age-specific incidence of acute appendicitis has different patterns in male and female. The incidence was highest in males aged 20-29 years whereas in females the highest incidence was observed in 10-19 years age group. A significant seasonal effect was also observed, with the rate of acute appendicitis higher in the summer months (p<0.006). The rate of false positive diagnosis was highest in the patients aged 0-9 years (p<0.0001). Of those correctly diagnosed, 85.5% had uncomplicated acute appendicitis; 8.3% had perforation; and others (6.2%) had acute appendicitis complicated with other situations. CONCLUSION: Appendicitis is more common in males, in those aged 20-29 years, and during the summer months. The age-specific incidence and sex ratio of acute appendicitis give the impression that epidemiologic features of acute appendicitis are different with worldwide data. However, the seasonal variation and false positive rate of acute appendicitis are in a good agreement with other studies.

Cross-sectional reference values for height, weight and body mass index of school children living in Tehran, Iran.

AIM: The aim of the study was to create reference values for weight, height and body mass index (BMI) of school children living in Tehran. METHOD AND SAMPLES: The study subjects consisted of 1,420 girls between 6 and 17 years of age and 1,515 boys between 6 and 15 years of age. Samples were collected by a multistage sampling method from schools in different areas of Tehran. All participants were established to be healthy and their height, weight and BMI evaluated. Reference standard values estimated by the LMS method using LMS Light software and 3rd, 5th, 10th, 25th, 50th, 75th, 90th, 97th and 85th (only for BMI) centiles were constructed and the results compared with US reference values. RESULTS: The centiles provided a good fit to the data. In boys, there were some significant differences of mean standard deviation scores (SDS) of height and BMI from zero, but there were no significant differences in weight. In girls, the mean SDS of height, weight and BMI were significantly lower than zero, especially for 7-9 years of age. Among 12-13-year-old girls, the mean SDS of height, weight and BMI came closer to zero, and the differences were not significant. Thereafter, although girls seemed to be shorter than US reference measures, their weight and BMI did not differ from reference values significantly. CONCLUSION: Our results for boys between 6 and 15 years are comparable with US reference values; however, the US reference values, especially for height, are not applicable for Iranian girls between 6 and 17 years.

Outcome of pediatric renal transplantation in Labfi Nejad Hospital, Tehran, Iran.

Kidney transplantation is the treatment of choice for children with end-stage renal disease. In Iran, a kidney transplantation program was started in the Labfi Nejad Hospital, Tehran in 1985. From 1985 to 2003, 278 children (mean age 11.6 years, 59.7% males) received their first renal transplant. All transplants were donations from live donors (12.5% live-related donors); 30.8% of patients were preemptively transplanted. The overall 1-year patient survival rate was 92% and the 5-year survival rate 74%. The median graft survival time was 7.2 years. The rate of graft survival was 88.8% at 1 year, 77% at 3 years, 67% at 5 years, 50% at 7 years, and 43% at 10 years after transplantation. The survival rate of patients and transplants improved significantly with time (p<0.05). In patients transplanted before 1997, the 5-year graft survival was 50% and 82% in patients transplanted after 1997. At the same time intervals, the frequency of acute rejection episodes was 66.6 versus 40.8% and of chronic rejection 50.5 versus 28.7%. The outcome in children below the age of 6 years was poor. Graft survival was negatively correlated with the frequency and an early time point of acute rejection episodes. The modus of transplantation (preemptive or postdialysis) did not influence the results. In conclusion, patient and graft survival in transplanted children significantly improved with time, thus reflecting greater medical and surgical experience, new immunosuppressive drugs, and better compliance.

Age of puberty in Iranian girls living in Tehran.

The aim of this study was to determine the age of appearance of secondary sexual characteristics in Iranian girls living in Tehran. A cross-sectional study was conducted between 2003 and 2004 on 1420 6-17-year-old females in different parts of Tehran. Data were collected on the basis of a multistage probability sampling. Secondary sexual characteristics were evaluated by inspection and palpation, and were recorded according to Tanner staging. The subjects were asked about the occurrence of menarche and the age of its onset. Generalized additive logistic modelling was used for the analysis of data. The median age (percentile 10-percentile 90) of Tanner 2 of breast development (B2) and Tanner 2 of pubic hair growth (P2) among 1136 girls was 9.74 years (8.23-11.94) and 10.49 years (8.86-12.17), respectively. The ages of the 2.5 percentile for B2 and P2 were 7.42 and 7.03 years, respectively, so the onset of puberty at < 7 years and 5 months is considered precocious in this population. The median age of menarche in 399 girls was 12.68 years (11.27-15.96).