A. R. Dehpour, PharmD, PhD
A. Javadian, MD
Vol 57, No 2 (2019)
Small interfering RNAs (siRNA) technology has shown great promise as a new class of therapeutic interventions for the treatment of cancer and other diseases. It is a remarkable endogenous pathway that can regulate sequence-specific gene silencing. Despite the excitement about possible applications of this biological process for sequence-specific gene regulation, the major limitations against the use of siRNA-based therapeutics are their rapid degradation by serum nuclease, poor cellular uptake, and rapid renal clearance following systemic delivery, off-target effects and the induction of immune responses. Many researchers have tried to overcome these limitations by developing nuclease-resistant chemically-modified siRNAs and a variety of synthetic and natural biodegradable lipids and polymers to enhance the efficacy and safety profiles of siRNA delivery. Ideal siRNA-based delivery systems for cancer therapy must be clinically suitable, safe and effective. In this review, we introduce the greatest challenges in achieving efficient RNAi delivery and discuss design criteria and various delivery strategies for cancer therapy, including chemical modifications, lipid-based nano-vectors, polymer-mediated delivery systems, conjugate delivery systems, and others.
Several studies point to an important role of neuroinflammation in Parkinson's disease (PD). Cognitive and memory impairments have been known in the early stages of PD. In the present study, we examined the effects of celecoxib (CLX), a selective inhibitor of cyclooxygenase-2 (COX-2), on hippocampus cell loss, passive avoidance memory and antioxidant status in a rat model of PD. We used the subcutaneous injection of 2.5 mg/kg/48h rotenone (ROT) for 4 weeks for induction of PD in a male Wistar rat. Animals were randomized to 4 groups (n=12): Control, sham, PD and PD+CLX group that receive celecoxib (20 mg/kg/day) for 4 weeks. Passive avoidance memory evaluated. We also determined the protective effect of CLX on a number of CA1 neurons in Nissl and TUNEL staining. Total antioxidant capacity (TAC) and malondialdehyde (MDA) a marker of lipid peroxidation in hippocampus assessed. Our findings indicated administration of CLX increase the passive avoidance memory (P<0.05), and by a decrease in apoptosis caused an increase in viable pyramidal neurons in CA1 hippocampus (P<0.01). On the other hand, CLX markedly reduced MDA level and increased TAC in the hippocampus of the PD model animal (P<0.05). It seems CLX with anti-inflammatory and antiapoptotic effect could prevent neurons loss and memory impairment which induced in PD.
Renin angiotensin (RAS), kallikrein kinin (KKS), and sex hormonal systems demonstrate a complex contribution in kidney circulation. This study was designed to investigate the role of angiotensin 1-7 (Ang 1-7) receptor (MasR) and of bradykinin B2 receptor (B2R) in renal blood flow (RBF) response to Ang 1-7 infusion in ovariectomized estradiol treated rats. The ovariectomized rats received intramuscular vehicle (group 1, OV) or estradiol valerate (500 µg/Kg/week) (group 2, OVE) for two weeks. Then each group was divided into two subgroups subjected to receive B2R antagonist (HOE-140, subgroup A), or MasR antagonist (A779) plus HOE-140 (subgroup B). RBF and renal vascular resistance (RVR) responses to graded Ang 1-7 infusion were determined. In condition of B2R alone blocking, RBF response to Ang 1-7 in OVE group was significantly greater than that of OV group (P=0.05), however this response difference was failed by co-blockades of MasR and B2R. Estradiol could promote RBF response to graded Ang 1-7 infusion in the absence of B2R alone, however when both receptors (MasR and B2R) were blocked the role of estradiol was limited.
Post anesthesia shivering which happens in some patients during recovery time after general anesthesia is followed by central hypothermia and peripheral vasoconstriction. In this study, the effect of opioidergic/nitrergic systems were determined on post anesthesia shivering in rat. Animals were cooled gently on a cold surface with indirect contact with a mixture of ice and water. Animals were treated with saline; methadone (a full opioid agonist, 10 mg/kg); naltrexone (an opioid receptor antagonist, 10 mg/kg); L-NAME (a nonselective nitric oxide synthase (NOS) inhibitor, 10 mg/kg). The core body temperature and the frequency of basal state- and post anesthetic-shivering were recorded using a stainless steel rectal probe (MLT-1403, AD Instruments®) and electromyography (EMG) electrodes connected to Animal Bio Amp (FE136, AD Instruments®) signal conditioner, respectively. Methadone administration reduced the frequency of shivering after anesthesia, while injection of naltrexone and L-NAME increased post anesthetic shivering compared to vehicle group. Co-administration of L-NAME and methadone showed a significant decrease the frequency of post anesthetic shivering. Furthermore, the temperature of shivering onset was reduced following methadone administration, which was blocked by injection of both naltrexone and/or L-NAME. To conclude, the findings of this study revealed the protective impact of methadone on post anesthesia shivering-induced with hypothermia dominated to nitrergic pathway effects in rat.
Patients with heart failure (HF) are frequently admitted for episodes of decompensation. Cardiac troponins are easily accessible biomarkers role of which for risk stratification of re-hospitalization among HF patients is less certain. We aimed to evaluate high-sensitive cardiac troponin I (hs-cTnI) levels among re-hospitalized patients with decompensated heart failure (D-HF). Consecutive subjects admitted with D-HF to 2 hospitals in Tehran, during the year 2014 were recruited. Excluded ones were patients with a suspected acute coronary syndrome or myocarditis/pericarditis, those with cardiopulmonary resuscitation/DC shock delivery, or major complications during or after hospitalization. Along with echocardiography parameters, level of hs-cTnI was checked at the first hour of hospitalization and 3 months after discharge. The patients were then categorized according to having or not having re-hospitalization during 3 months post discharge. A total of 97 patients were finally recruited. Among re-hospitalized patients, Left ventricular (LV) ejection fraction was significantly lower (38±14 % vs. 50 ± 12%; P=0.001), and LV end-systolic dimension was significantly higher (44±9 mm vs. 38±11 mm; P=0.012) compared to the other group. Moreover, levels of hs-cTnI were significantly higher among the re-hospitalized patients, both at initial visit (0.66±0.43 ng/ml vs 0.51±0.14 ng/ml, respectively; P=0.017) and at 3 months (0.59±0.48 ng/ml vs 0.48±0.23 ng/ml, respectively; P=0.030). This prospective study demonstrated that levels of hs-cTnI (both at the base and at follow up) are higher among patients who readmitted during 3 months of hospitalization for D-HF.
Advanced breast cancer is a common disease among female gender in the world. There is a correlation between cancer and hypercoagulation. In a cancer state, there is an increase in the level of cross-linked fibrin degradation product (d-dimer) which indicates systemic activation of fibrinolysis and hemostasis. So, there is a relation between increase d-dimer value and advanced breast disease. To study the relation between preoperative plasma d-dimer level and tumor extension, choose the proper option of treatment, and to decrease morbidity and mortality in patients with breast carcinoma, a prospective study (cohort study) was done at Baghdad teaching hospital (department of surgery) from Jan 2014 to Jan 2016. Seventy patients were categorized into two equal groups, group one with breast carcinoma, and group two with benign breast tumor. Plasma d-dimer levels were compared for each group and in relation to (tumor size, stage, grade, lymphovascular invasion, and lymph nodes involvement). The d-dimer level was normal in group two (<0.25 mg/l) and high in group one in other words, the d-dimer level was increasing in advanced breast carcinoma group with enlarged tumor size, higher stage and grade, lymphovascular invasion and lymph nodes’ involvement. Plasma d-dimer levels were a good prognostic factor in breast carcinoma especially in advanced breast carcinoma, and it could be considered a factor for clinical stage progression lymphovascular invasion, and metastasis.
We aimed to define Metabolic Syndrome (METs) from different viewpoints to determine the most appropriate method that could be used for early METs' diagnosis in general population and treat them immediately. This study was an analytic cross-sectional study which was conducted on 725, twelve year-old-girls and boys from Rasht city in Iran. METs was defined based on 7 different methods. Data were reported by descriptive statistics (number, percent, mean, and standard deviation) and analyzed by Cohen's kappa coefficient correlation and chi-square in SPSS version 19. The highest and lowest percentages of METs were obtained by DE Ferranti (17.5%) and viner et al., (0.8%) methods, respectively. Results showed that viner et al., had the highest degree of agreement with NCEP ATPIII and the lowest with DE Ferranti. Furthermore, De Ferranti showed the highest degree of agreement with NHANESIII and the lowest with Viner et al., According to results, the identification of the cut off points of obesity could help to promote public health care.
Ovarian tumors are rare in childhood and adolescent age. A 14-year-old girl presented with abdominal distention and mild cyclical abdominal pain since 3 months ago. There was an abdominal distention, and huge firm mass was palpated from pelvis to epigastric region. Abdominal ultrasonography revealed normal uterus and large multiloculated adnexal mass with multiple fine septations. Laparotomy was performed, and the ovarian mucinous borderline tumor was reported in frozen section biopsy. Exploration of other abdominopelvic organs revealed no other pathological signs. The final pathological report showed the right ovarian mucinous borderline tumor. Although the mucinous ovarian borderline tumor is a rare condition in adolescent age, pelvic mass, especially with solid or nodular component, must arise this diagnosis, and exploratory laparotomy with comprehensive surgical staging with regard to fertility preservation is warranted.
Gastrointestinal Stromal Tumors (GISTs) are the most common gastrointestinal mesenchymal tumors and in 80% of the cases are associated with KIT activating mutations. The incidence of GISTs is generally 10-20 cases per million population, which turn out to be malignant in 20-30% of cases. GISTs can be large and present with dysphagia, even though they are usually small and asymptomatic. A 67-year-old woman was referred to the hospital complaining of pain and burning in epigastric area and left flank; the patient had experienced a weight loss within one month before the admission. Primary investigations upon upper endoscopy revealed a submucosal mass in distal part of esophagus, and nodularity and erythema in stomach. But through more examinations by MDCT of Abdomen and Pelvis, a mass measuring 20*33 mm in cardiac and lesser curvature submucosa, without lymphadenopathy was reported, that could suggest GIST. This mass was excised with normal margins via wide local excision, bilayer cardiplasty and funduplication. The patient was hospitalized for 10 days after surgery, and was discharged with good general condition. In follow-up, there wasn’t any sign of dysphagia and dyspepsia within 24 months. In the patients suffering from GIST, the tumor location appears to have the most important role on deciding whether to perform local excision or not. Treatment of GISTs locating near gastroesophageal junction (GE junction) is still challenging. Using an appropriate therapeutic method is crucial in improving the patient’s quality of life. Therefore, wide local excision followed by bilayer cardiplasty and funduplication, could be considered as the appropriate therapeutic protocol in such same situations due to elimination of post total gastrectomy adverse effects and the tumor relapse.
Nasal foreign bodies are usually received in otolaryngology practice. Although more frequently seen in pediatric patients, also they can affect adults, specifically those with mental retardation or any psychiatric problems. We presented an unusual case of the nasal foreign body, an eraser rhinolith in a 17-year-old boy with mild mental retardation presented with long-lasting nasal obstruction but no chronic infection or epistaxis. Computed tomography revealed a peripherally calcified sub-mucosal round mass in the left nasal cavity. After surgery, a round shape foreign body that looked like an eraser piece was removed from the nasal cavity. Rhinolith can present just with nasal obstruction. With properly diagnosed and appropriate surgery, all rhinoliths can be removed and complication of extraction can be minimized.
Melanotic neuroectodermal tumor of infancy (MNTI) is a rare and distinctive neoplasm of early infancy with rapid expansile growth and a high rate of recurrences. Most commonly the lesion affects the maxilla of infants during the first year of life, but it may also occur in the mandible, skull, brain, epididymis, and other rare locations. Common treatment methods’ include surgical excision and resection of the tumor. The aim of this article was to show the diagnosis and treatment of a 7-month-old patient with melanotic neuroectodermal tumor occurred in the anterior mandible and to demonstrate the effectiveness of the neoadjuvant chemotherapy.
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