Acta Medica Iranica
Volume:56 Issue: 10, Oct 2018

Intrahippocampal amyloid β (Aβ) negatively affects synaptic plasticity with subsequent impairment of learning and memory. Trigonelline is an alkaloid commonly found in fenugreek seeds and coffee beans with neuroprotective property and a promising agent for management of neurodegenerative disorders like Alzheimer’s disease (AD). In the present study, the possible beneficial effect of trigonelline on the improvement of learning and memory and synaptic plasticity was evaluated in Aβ (1-40) rat model of AD. For modeling AD, aggregated A𝛽 (1-40) (10 𝜇g/2 𝜇l for each side) was bilaterally microinjected into the hippocampal CA1 area. Trigonelline was administered p.o. at a dose of 100 mg/kg. The results showed that trigonelline pretreatment of Aβ-microinjected rats ameliorates learning and memory deficit in passive avoidance task and spatial memory impairment in Morris water maze (MWM) paradigm. It also improved population spike (PS) amplitude and field excitatory post-synaptic potential (fEPSP) slope following application of high frequency stimulation (HFS) to induce long-term potentiation (LTP) in medial perforant-dentate gyrus pathway as an index of synaptic plasticity. Additionally, trigonelline mitigated hippocampal activity of acetylcholinesterase (AChE). In summary, trigonelline pretreatment of intrahippocampal Aβ-microinjected rats could ameliorate learning and memory impairment, partly through restoring hippocampal synaptic plasticity and AChE and it may be suggested as an adjunct and promising oral bioactive therapeutic agent that may prevent memory deterioration in AD.

Superoxide dismutase-1 (SOD1, OMIM: 147450, copper-zinc superoxide dismutase) is one of the major antioxidant enzymes, which plays an important role in clearance of reactive oxygen species. A common genetic polymorphism of 50 bp insertion/deletion (Ins/Del) in the promoter region of the SOD1 has been reported. The purpose of the present study was to investigate the association between this polymorphism and the risk of opium (OD) and methamphetamine (MD) dependency. The present report was consisted of two case-control studies. The first study consisted of 143 OD subjects and 570 healthy controls. The second study consisted of 65 cases with MD and 635 controls. The controls were selected randomly from the healthy blood donors. Genotyping were carried out using PCR based method. Statistical analysis indicated that neither the Ins/Del (OR=1.06, 95% CI: 0.69-1.62, P=0.788) nor the Del/Del (OR=0.57, 95% CI: 0.13-2.55, P=0.464) genotypes were associated with the risk of OD. Although the frequency of the Ins/Del genotype was lower among methamphetamine-dependent persons compared to healthy control subjects, there was no significant association between the Ins/Del polymorphism and the risk of MD (OR=0.82, 95% CI: 0.44-1.53, P=0.547). The present findings demonstrated that the SOD1 50bp Ins/Del polymorphism is not associated with the risk of OD and MD.

Acute lymphoblastic leukemia (ALL) is a malignant transformation and proliferation of lymphoid progenitor cells in the bone marrow, blood and extramedullary sites and the second most common acute leukemia in adults. While dose-intensification strategies have led to a significant improvement in outcomes for pediatric patients, the prognosis for the elderly remains very poor. Aberrant or excessive expression of cytokines may be related to the pathogenesis of acute leukemia. TGF-β is a cytokine that plays a role in regulating various cellular processes such as growth, proliferation, and apoptosis. We evaluated the expression of TGF-β mRNA in adults with ALL compared to the control and its relationship with disease-related prognostic factors. Bone marrow specimens were obtained from 90 newly-diagnosed adults with ALL and 33 healthy adults. After immunophenotyping by flow cytometry, RNA was extracted, and RQ-PCR was done. Our result showed that from all patients, 63 (70%) were identified as B-ALL and 27(30%) as T-ALL. TGF-β transcript levels in both T-ALL and B-ALL patients showed a significant decrease compared to the control group (P < 0.001). However, the expression of the TGF-β transcripts was not different between the different immunophenotypic subtypes (P=0.54). The gene expression level of TGF-β was not correlated with age (P=0.47), gender (P=0.29), ALL subtypes (P=0.54), the percentage of bone marrow blasts (P=0.92) and peripheral blood leukocyte count (P=0.38) of ALL patients. In conclusion, since TGF-β has a tumor suppressor role, it seems that leukemic cells may use TGF-β down-regulation to be more freely proliferated and evolve the clone.

Hypertriglyceridemia is a common form of dyslipidemia and is associated with several comorbidities, such as increased risk of pancreatitis and cardiovascular diseases (CVD). The white blood cell (WBC) count is a non-specific inflammatory marker associated with a wide variety of diseases such as diabetes, hypertension, and atherosclerotic cardiovascular disease. The objective of this study was to perform a gender-stratified examination of the association between hypertriglyceridemia and hematological parameters in a large sample of Iranian population. The triglyceride (TG) levels and hematological parameters were measured in 9,780 participants (40% males and 60% females) aged 35-65 years, enrolled in a population-based cohort (MASHAD) study in northeastern Iran. Participants were stratified into three groups based on the definition of hypertriglyceridemia: TG<150 mg/dl (n=6521), TG=150-199 mg/dl (n=1597), and TG≥200 mg/dl (n=1662). A complete blood count (CBC) was obtained for all the subjects. The mean WBC count increased with increasing severity of hypertriglyceridemia among both men and women. Participants with high and very high TG levels had significantly higher WBC count, RBC count, platelet count, hemoglobin, hematocrit, and mean corpuscular hemoglobin concentration and significantly lower RDW. After performing multivariate logistic regression, WBC count and RDW were independently related to hypertriglyceridemia. In conclusion, hypertriglyceridemia is associated with elevated WBC count which may partly explain the observed association between hypertriglyceridemia and CVD.

The OCT1 and TGIFLX transcription factors are members of homeodomains whose expressions have been implicated in normal and abnormal development. However, the expression of TGIFLX and OCT1 in colorectal cancer is unknown. This study aimed to detect the expression of OCT1 and TGIFLX in clinical samples of colorectal cancer. Twenty-six pairs of colorectal cancer tissue and adjacent non-tumoral tissue were obtained at the time of surgery from patients with colorectal cancer. The expression of TGIFLX and OCT1 was detected by real time reverse transcriptase polymerase chain reaction (RT-PCR). OCT1 was down-regulated in colorectal carcinoma samples in both males (58.33%) and females (57.14%). By contrast, TGIFLX was mainly (41.63%) expressed in colorectal tumors of males' samples but not in para-neoplastic normal tissues. OCT1 expression was not significantly associated with the gender and site of primary tumor (P>0.05), but the expression of TGIFLX was associated with male patients (P<0.05). In conclusion, dysregulation of OCT1 and TGIFLX genes might be novel prognostic biomarkers for patients with colorectal cancer.

Esophageal atresia (EA) is a rare congenital anomaly that may be isolated or associated with other anomalies requiring prompt medical and surgical planning for optimal result. This study was conducted to show our recent experience on the outcome of treated patients in two hospitals affiliated to Tehran University of Medical Sciences (TUMS). From January 2008 to May 2013 records of 43 neonates patients (23 male) with EA admitted in 2 children centers and all related data including demographic, diagnostic associated anomalies, surgical approaches, birth weight, mortality, and complications were collected. Inability of feeding and swallowing was the most common symptoms (in 90,6%), associated CHD (44%), and Type C (EA) was the most common type of EA observed in 86% patients, The mortality rate was 4.7% and most common complication was anastomotic stricture (AS) in 60% of patients. Our study showed that despite improvements in management and survival of an infant with (EA), still sepsis, aspiration pneumonia, prematurity, and low birth weight and severe Congenital Heart Disease (CHD) were independent etiology of death and birth weight < 2.500 gr has a significant effect on the occurrence of postoperative complications.

It has been proved that rheumatoid arthritis (RA) is linked to dyslipidemia and the risk of cardiovascular complications is higher in these patients. The aim of this study was to evaluate dyslipidemia in RA patients. In this study, RA patients were enrolled regarding the inclusion and exclusion criteria. Their demographic information and medication profiles were evaluated. Clinical assessments were performed by evaluation of disease activity score (DAS28) and visual analogue scale. Moreover, laboratory investigations of lipid profile including triglycerides (TG), total cholesterol (Chol), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were performed. From a total of 150 patients with the mean age of 54.9±16.8 years, 65.3% were diagnosed with dyslipidemia. Females in menopausal ages had a higher prevalence of dyslipidemia as well as patients with longer disease duration. Mean serum HDL, LDL, Chol, and TG were 52.76±13.8, 96.65±21.6, 177.26±38.9, and 128.04±33.9, respectively. Considering DAS28, 100% of the patients with high disease activity were diagnosed with dyslipidemia. In the moderate and low disease activity groups and also patients in remission the ratio was 77.02%, 66.66%, and 43.75%, respectively. According to the results, patients under treatment with prednisolone and methotrexate were more affected by dyslipidemia than those with prednisolone, methotrexate, and hydroxychloroquine. Moreover, in the patients under prednisolone, methotrexate, and leflunomide treatment, the prevalence of dyslipidemia was significantly lower than those used only prednisolone and methotrexate. Altogether, it is necessary to have more clinical suspicion towards dyslipidemia and its complications in the patients with greater number of affecting factors.

Spinal manipulation is a manual technique commonly used for the treatment of low back pain. The physiologic mechanisms of the spinal manipulation are largely unknown. One basic physiologic response for spinal manipulation is an alteration in motoneuronal activity, as assessed by the Hoffmann reflex (H-reflex) technique. The purpose of this study was to determine the effect of spinal manipulation on the amplitude and onset latency of H-reflex and on H/M amplitude ratio in patients with low back pain. Fifty-Eight patients with low back pain aged between 20-60 years, who had no exclusion criteria were included. Tibial nerve H-reflex and M wave were recorded before and after Lumbosacral spinal manipulation. Lumbosacral manipulation significantly decreased the amplitude of the H-reflex and H/M amplitude ratio (P<0.05). It had no significant effect on H-reflex latency or M wave amplitude and latency (P>0.05). Lumbosacral manipulation produces attenuation of alpha motoneuronal excitability. These findings support this theory that manual spinal therapy can lead to a reduction in muscle tone.

The ATP8A2 protein is mainly located in the brain and takes part in the lipid flipping process. Mutations in the ATP8A2 gene and chromosomal translocations that interfere with the ATP8A2 gene product have been reported in association with global developmental delay and hypotonia. Here, we will report a three-year-old male presented with major phenotypic features of dysequilibrium syndrome (DES), including severe hypotonia, global developmental delay, speech problem, and strabismus. Whole exome sequencing revealed a homozygous in-frame deletion in the ATP8A2 gene (c.1286_1288delAGA, p.Lys429del). This ATP8A2 variant has not been reported yet and seems to be linked to the phenotypic features of dysequilibrium syndrome.

Schwannoma is a benign encapsulated tumor of the nerve sheath. Amongst other sites, it develops in the posterior mediastinum in the costovertebral sulcus. We herein present a case of a 68-year-old woman with an incidental finding of a subcarinal mass. Radiological and histopathological studies were suggestive of schwannoma. Therefore, the mass was completely resected through a right thoracotomy, and a definite histopathological diagnosis was established. Although the subcarinal area is a rare site for this tumor to appear, the schwannoma should be considered as part of the differential diagnosis of lesions in the subcarinal region. Treatment of choice is the nerve-sparing surgical excision of the mass with excellent prognosis. A review of the literature on this topic was performed.

Mastocytosis is characterized by the accumulation of mast cells in different tissues either in the skin or extracutaneous organs. Herein, a 13-year-old girl is presented who suffered from intermittent abdominal pain, nausea, diarrhea with erythematous, and papulous cutaneous lesion. She had a history of same lesions from the age of four years. Since 8 months ago, the patient presented with digestive complaints. The histopathological examination of the cutaneous lesions approved the diagnosis of mastocytosis. H1 and H2 antagonists were prescribed for her, while a mast cell stabilizer for digestive and cutaneous symptoms was also utilized, which improved the signs and symptoms of the patient.