Identification of chemical compounds of <em>Nardostachys Jatamansi </em>essence available in Iran

Introduction: With regard to using drugs with plant origin and with the aim of suitable use of these types of drugs and preventing them to be abused, it is necessary to determine the standards of these plants. The aim of the present study was to identify and study chemical compounds of Nardostachys Jatamansi essence in Iran and define monograph of this plant for the Iranian plant pharmacopeia. Methods: In an experimental study the Nardostachys Jatamansi specimen was prepared from the market in Iran. The essence of the plant was prepared by the hydro-distillation in Clevenger apparatus. Essence was obtained as a greenish yellow oil layer with the 0.07 yield. The essence compounds were identified quantitatively by Gas Chromatography-Mass Spectroscopy (GC/MS) method. Results: Totally, 29 compounds were identified in Nardostachys Jatamansi essence. The retention indexes (RI) were only similar with overall standard values in two compounds like mesitylene and P-cymene. In this line the RI values about three compounds of valerenic acid, palmitic acid, and valerenyl isovalerate were determined significantly higher than standard values of RI. Conclusion: The essence prepared from the Nardostachys Jatamansi plant in Iran was different in terms of some compounds and components including valerenic acid, palmitic acid, and valerenyl isovalerate and so it is necessary to identify and register quality and quantity characteristics of compounds available in this plat in the Iranian medicinal plants pharmacopeia.</p

Hepatitis A virus and Hepatitis E virus seroprevalence among blood donors in Tehran, Iran

Background: Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are both transmitted by the fecal-oral route and are known as the leading causes of acute viral hepatitis in the world, especially in developing countries. There is a lack of updated data on HAV and HEV seroprevalence in Iran. Objectives: The aim of this study was to determine the seroprevalence of HAV and HEV among a group of blood donors in Tehran, Iran. Materials and Methods: A cross-sectional study was performed from July 2014 to December 2014, on a total of 559 blood donors referred to the Tehran blood transfusion center. The serum samples were tested for antibodies to HAV and HEV, using the enzyme-linked immunosorbent assay. Results: In the present study, 536 (95.9) cases were male and 23 (4.1) female with mean age of 38 years. Out of 559 blood donors, 107 (19.1) were first-time donors, 163 (29.2) lapsed donors and 289 (51.7) regular donors. Anti-HAV was found in 395 (70.7) and anti-HEV in 45 (8.1) of the blood donors. The HAV and HEV seroprevalence increased by age. There was no significant difference between genders in terms of anti-HAV and anti-HEV status. The HAV and HEV seroprevalence was significantly related to the level of education, where the donors with higher level of education had lower rate of HAV and HEV seroprevalence. The HAV and HEV seroprevalence was significantly higher in regular and lapsed donors than in first-time donors. Conclusions: The present study showed that both HAV and HEV infections are still endemic in Iran. © 2016, Kowsar Corp

Detection of hepatitis B virus covalently closed circular DNA in the plasma of Iranian HBeAg-negative patients with chronic hepatitis B

Background: Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is a marker of HBV replication in the liver of patients infected with HBV. Objectives: This study aimed to investigate the association between the presence of cccDNA in the plasma samples of Iranian treatment-naive patients with chronic hepatitis B infection and HBV viral load and HBsAg levels. Patients and Methods: From April 2012 to May 2015, 106 treatment-naive patients with chronic hepatitis B infection were enrolled in this cross-sectional study. The HBsAg titer was measured by the Roche HBsAg II assay on the Cobas e411 system, and HBV DNA quantitation was performed using the COBAS TaqMan 48 kit. Real-time polymerase chain reaction was performed for the detection of HBV cccDNA. Results: The mean (SD) age of the patients was 41.1 ± 12.4 years (range, 20 - 62 years). From a total of 106 study participants, 67 (63.2) were males. The HBV cccDNA was detected in plasma specimens in 19 (17.9) out of the total 106 patients, and a significant relationship was found between the presence of cccDNA in plasma sample of males (23.9) and females (7.7) (P = 0.039). Also, a significant correlation was found between the presence of cccDNA in plasma sample of the patients and HBV viral load level (P < 0.0001) and HBsAg titer (P = 0.0043). Conclusions: This study showed that cccDNA can be detected in the plasma specimen of 17.9 of Iranian treatment-naive patients with chronic hepatitis B infection. Therefore, designing prospective studies focusing on the detection of cccDNA in these patients would provide more information. © 2015, Kowsar Corp

Efficacy of tenofovir disoproxil fumarate therapy in nucleoside-analogue naive Iranian patients treated for chronic hepatitis B

Background: Tenofovir disoproxil fumarate (TDF) is a new effective treatment option for patients with chronic hepatitis B (CHB). Objectives: To evaluate TDF efficacy in nucleos(t)ide analogues (NAs)-naive Iranian patients with CHB. Patients and Methods: The NA-naive patients received TDF for at least six months. The primary endpoint was the proportion of patients achieving a complete virological response (CVR) during the treatment. Multivariate Cox regression analysis determined predictive factors independently associated with the time to CVR. The secondary endpoints were biochemical and serological responses, frequency of virological breakthrough, genotypic resistance development, safety and tolerability. Results: In all, 93 patients (64.5 hepatitis B e antigen HBeAg-negative) were eligible. Of these, 70 patients completed 24 months of treatment. The cumulative CVR rates in HBeAg-negative and HBeAg-positive patients were 87% versus 53% at 24 months, respectively. The multivariate Cox regression model showed only HBeAg positivity at baseline and a high baseline HBV DNA level were independent factors predicting a CVR. No patient achieved hepatitis B surface antigen (HBsAg) and HBeAg loss or seroconversion and no virologic breakthrough occurred. A new amino acid substitution (rtD263E) was observed to develop in 60% of patients with viremia. Conclusions: The cumulative CVR rates showed that patients with HBeAg-negative have better virologic respond than those with HBeAg-positive during the same period. The rtD263E mutation might be associated with partial resistance to TDF. © 2015, Kowsar Corp

Muscle-specific overexpression of AdipoR1 or AdipoR2 gives rise to common and discrete local effects whilst AdipoR2 promotes additional systemic effects

Hypoadiponectinemia and adiponectin resistance are implicated in the aetiology of obesity-related cardiometabolic disorders, hence represent a potential therapeutic axis. Here we characterised the effects of in vivo electrotransfer-mediated overexpression of the adiponectin receptors, AdipoR1 or AdipoR2, into tibialis anterior muscle (TAM) of lean or obese mice. In lean mice, TAM-specific overexpression of AdipoR1 (TAMR1) or AdipoR2 (TAMR2) increased phosphorylation of AMPK, AKT and ERK and expression of the insulin responsive glucose transporter glut4. In contrast, only TAMR2 increased pparα and a target gene acox1. These effects were decreased in obese mice despite no reduction in circulating adiponectin levels. TAMR2 also increased expression of adipoQ in TAM of lean and obese mice. Furthermore, in obese mice TAMR2 promoted systemic effects including; decreased weight gain; reduced epididymal fat mass and inflammation; increased epididymal adipoQ expression; increased circulating adiponectin. Collectively, these results demonstrate that AdipoR1 and AdipoR2 exhibit overlapping and distinct effects in skeletal muscle consistent with enhanced adiponectin sensitivity but these appear insufficient to ameliorate established obesity-induced adiponectin resistance. We also identify systemic effects upon TAMR2 in obese mice and postulate these are mediated by altered myokine production. Further studies are warranted to investigate this possibility which may reveal novel therapeutic approaches

Laparoscopic versus open peritoneal dialysis catheter insertion, the LOCI-trial: a study protocol

Background: Peritoneal dialysis (PD) is an effective treatment for end-stage renal disease. It allows patients more freedom to perform daily activities compared to haemodialysis. Key to successful PD is the presence of a well-functioning dialysis catheter. Several complications, such as in- and outflow obstruction, peritonitis, exit-site infections, leakage and migration, can lead to catheter removal and loss of peritoneal access. Currently, different surgical techniques are in practice for PD-catheter placement. The type of insertion technique used may greatly influence the occurrence of complications. In the literature, up to 35% catheter failure has been described when using the open technique and only 13% for the laparoscopic technique. However, a

Probabilistic Computation in Human Perception under Variability in Encoding Precision

A key function of the brain is to interpret noisy sensory information. To do so optimally, observers must, in many tasks, take into account knowledge of the precision with which stimuli are encoded. In an orientation change detection task, we find that encoding precision does not only depend on an experimentally controlled reliability parameter (shape), but also exhibits additional variability. In spite of variability in precision, human subjects seem to take into account precision near-optimally on a trial-to-trial and item-to-item basis. Our results offer a new conceptualization of the encoding of sensory information and highlight the brain’s remarkable ability to incorporate knowledge of uncertainty during complex perceptual decision-making

Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study

Background: The strategy of watch and wait (W&W) in patients with rectal cancer who achieve a complete clinical response (cCR) after neoadjuvant therapy is new and offers an opportunity for patients to avoid major resection surgery. However, evidence is based on small-to-moderate sized series from specialist centres. The International Watch & Wait Database (IWWD) aims to describe the outcome of the W&W strategy in a large-scale registry of pooled individual patient data. We report the results of a descriptive analysis after inclusion of more than 1000 patients in the registry. Methods: Participating centres entered data in the registry through an online, highly secured, and encrypted research data server. Data included baseline characteristics, neoadjuvant therapy, imaging protocols, incidence of local regrowth and distant metastasis, and survival status. All patients with rectal cancer in whom the standard of care (total mesorectal excision surgery) was omitted after neoadjuvant therapy were eligible to be included in the IWWD. For the present analysis, we only selected patients with no signs of residual tumour at reassessment (a cCR). We analysed the proportion of patients with local regrowth, proportion of patients with distant metastases, 5-year overall survival, and 5-year disease-specific survival. Findings: Between April 14, 2015, and June 30, 2017, we identified 1009 patients who received neoadjuvant treatment and were managed by W&W in the database from 47 participating institutes (15 countries). We included 880 (87%) patients with a cCR. Median follow-up time was 3·3 years (95% CI 3·1–3·6). The 2-year cumulative incidence of local regrowth was 25·2% (95% CI 22·2–28·5%), 88% of all local regrowth was diagnosed in the first 2 years, and 97% of local regrowth was located in the bowel wall. Distant metastasis were diagnosed in 71 (8%) of 880 patients. 5-year overall survival was 85% (95% CI 80·9–87·7%), and 5-year disease-specific survival was 94% (91–96%). Interpretation: This dataset has the largest series of patients with rectal cancer treated with a W&W approach, consisting of approximately 50% data from previous cohort series and 50% unpublished data. Local regrowth occurs mostly in the first 2 years and in the bowel wall, emphasising the importance of endoscopic surveillance to ensure the option of deferred curative surgery. Local unsalvageable disease after W&W was rare. Funding: European Registration of Cancer Care financed by European Society of Surgical Oncology, Champalimaud Foundation Lisbon, Bas Mulder Award granted by the Alpe d'Huzes Foundation and Dutch Cancer Society, and European Research Council Advanced Grant

Fabrication of Poly Hydroxybutyrate-Polyethylene Glycol-Folic Acid nanoparticles loaded by paclitaxel

In this study drug (paclitaxel)-loaded nanoparticles of poly hydroxybutyrate-polyethylene glycol-folic acid (PHB-PEG-FOL) were prepared by using an oil-in-water (O/W) emulsion-solvent evaporation method. The functionalization and conjugation steps in the chemical synthesis were confirmed using Fourier transform infrared (FTIR) and nuclear magnetic resonance tests (1H NMR). Morphology of nanoparticles was evaluated by scanning electron microscopy (SEM). Nanoparticles were characterized by particle size analyzer. Between two samples containing drug, the lower doses showed more homogeneous distribution, and the lowest aggregation. The drug release profiles showed a two-phase release including initial rapid release and a continuous release. MG63 cells were used to evaluate cytotoxicity. The cytotoxicity of PHB-PEG-FOL nanoparticles with drug against cancer cells was much higher and longer than free drug sample. These nanoparticles were successfully synthesized as a novel system for targeted drug delivery against cancer cells. © 2016 Bentham Science Publishers