Cardiovascular Complications of Acute Amphetamine Abuse : Cross-sectional study

Objectives: This study aimed to evaluate cardiovascular complications among patients who abuse amphetamines. Methods: This cross-sectional study took place between April 2014 and April 2015 among 3,870 patients referred to the Toxicology Emergency Department of Baharlou Hospital, Tehran University of Medical Sciences, Tehran, Iran. Those with clinical signs of drug abuse and positive urine screening tests were included in the study, while cases of chronic abuse were excluded. Cardiac complications were evaluated via electrocardiography (ECG) and transthoracic echocardiography. Results: A total of 230 patients (5.9%) had a history of acute amphetamine abuse and positive urine tests. Of these, 32 patients (13.9%) were <20 years old and 196 (85.2%) were male. In total, 119 (51.7%) used amphetamine and methamphetamine compounds while 111 (48.3%) used amphetamines with morphine or benzodiazepines. The most common ECG finding was sinus tachycardia (43.0%), followed by sinus tachycardia plus a prolonged QT interval (34.3%). Mean creatine kinase-MB and troponin I levels were 35.9 ± 4.3 U/mL and 0.6 ± 0.2 ng/mL, respectively. A total of 60 patients (26.1%) were admitted to the Intensive Care Unit. The majority (83.3%) of these patients had normal echocardiography results. The mean aortic root diameter (ARD) was 27.2 ± 2.8 mm. Abnormalities related to the ARD were found in 10 patients (16.7%), three of whom subsequently died. Conclusion: According to these findings, cardiac complications were common among Iranian patients who abuse amphetamines, although the majority of patients had normal echocardiography and ECG findings

Research Paper: Sex Determination Based on Radiographic Examination of Metatarsal Bones in Iranian Population

Background: In forensic medicine, sex can be determined by studying human skeletal remains. This study aimed to evaluate the reliability of metatarsal bones in sex determination in Iranian population. Methods: A total of 184 healthy individuals (103 males and 81 females) were enrolled in the study. The sample was divided into three age groups: 20-34, 35-49, and ≥50 years. The length, width, length to width ratio (L/W), and length by width (L×W) product of sample’s right foot metatarsal bones were measured using their radiographic images.Results: The differences of length, width, L/W ratio, and L×W between two sexes were significant in all age groups (P<0.001). First metatarsal L×W had sensitivity and specificity of 85.4% and 88.8%, respectively, but the mean total L×W value of metatarsal bones had sensitivity and specificity of 94.2% and 78%, respectively. Conclusion: The first and the mean L×W values of all metatarsal bones had the highest accuracy for discriminating sexes (86.9% and 85.2%). The first metatarsal width and mean width of all metatarsal bones had an accuracy of 82.6% and 84.2%, respectively. In forensic medicine, these indexes can be used for sex-differentiation

Wharton’s jelly mesenchymal stem cells attenuate global hypoxia-induced learning and memory impairment via preventing blood-brain barrier breakdown

Objective(s): Intracerebroventricular (ICV) injections of mesenchymal stem cells (MSCs) may improve the function and structure of blood-brain barrier (BBB), possibly by preserving the BBB integrity. This study examined the impact of Wharton’s jelly (WJ)-MSCs on cognitive dysfunction and BBB disruption following a protracted hypoxic state.Materials and Methods: Twenty-four male Wistar rats were randomly studied in four groups: Control (Co): Healthy animals, Sham (Sh): Rats were placed in the cage without hypoxia induction and with ICV injection of vehicle, Hypoxic (Hx)+vehicle: Hypoxic rats with ICV injection of vehicle (5 μl of PBS), and Hx+MSCs: Hypoxic rats with ICV injection of MSCs. Spatial learning and memory were evaluated one week after WJ-MSCs injection, and then animals were sacrificed for molecular research.Results: Hypoxia increased latency and lowered the time and distance required reaching the target quarter, according to the findings. Furthermore, hypoxic rats had lower gene expression and protein levels of hippocampus vascular endothelial (VE)-cadherin, claudin 5, and tricellulin gene expression than Co and Sh animals (P<0.05). Finally, administering WJ-MSCs after long-term hypoxia effectively reversed the cognitive deficits and prevented the BBB breakdown via the upregulation of VE-cadherin, claudin 5, and tricellulin genes (P<0.05).Conclusion: These findings suggest that prolonged hypoxia induces spatial learning and memory dysfunction and increases BBB disruption, the potential mechanism of which might be via reducing VE-cadherin, claudin 5, and tricellulin genes. Hence, appropriate treatment with WJ-MSCs could reverse ischemia adverse effects and protect the BBB integrity following prolonged hypoxia

Research Paper: Using Subpubic Angle in Sex Determination and Stature Estimation: An Anthropometric Study on Iranian Adult Population

Background: Pelvic bone has important sex determining features. However, anthropometric reference values vary by study population. This study aimed to determine the accuracy of subpubic angle for sex determination and height estimation in Iranian adults.Methods: In this study, the subpubic angle in the digital pelvic radiographs of 325 Iranian adults (199 males and 126 females) and their standing heights were measured. Then, the relation of subpubic angle with sex and stature was evaluated. Results: The mean(SD) subpubic angle of the studied population was 116.3 (23.7) degrees. Subpubic angle was significantly wider (P&lt;0.001) in females [140.5(14.3) degrees] compared to males [101.0(13.3) degrees]. Moreover, we observed a significant decrease (P&lt;0.001) in females’ subpubic angle with an increase in age. A significant reverse correlation (P&lt;0.01) was also observed between the subpubic angle and height (r=0.416). Conclusion: This study showed that the mean subpubic angle in Iranian adults is different from the average in other populations. Our reference values can be used in forensic identification

Isolation and localization of cells expressing Sca-1 in the Adult Mouse Ovary: An evidence for presence of Mesenchymal Stem cells

Objective: Recently growing evident declared that ‘neo-oogenesis’ continues in mature female life span and simultaneously another studies confirmed the presence of spermatogonial stem cells (SSCs). Even though there is agreement between scientist about SSCs population in male gender but on the other side ovarian stem cells have received raising challenges regarding the existence in the surface epithelium of ovary. Mesenchymal stem cells (MSCs) are the most applicable source of stem cells and the common marker of MSCs is Sca-1 so the purpose of this study was to clarify the incidence of stem cells in the surface epithelium of ovary Methods: forty C57BL6 mice were sacrificed and the ovary carefully excised from its surrounding fat tissue, after mechanical and enzymatic digestion cells were stained with Sca1 to estimate the incidence of positive stem cells (SCs) population fluorescence activated cell sorting (FACS). Part of digested cells used for RT-PCR, also histological section prepared for immunohistochemical (IHC) staining of Sca-1 in ovarian surface epithelium (OSE) FACS. Results: The gene expression of Sca-1 was confirmed in the ovarian tissue. As well, localization of Sca-1 positive cells was detected in the germinal layer of ovary and epithelial granular layer of primordial follicles. Moreover, we successfully could isolated the Sca-1positive cells through Conclusion: The present work findings confirmed an inclusive stem cell population in the ovary which can be a strong evident for regeneration of ovarian tissue in either purpose of ovulation scar and neo-oogenesis

Streptozotocin induced oxidative stress, innate immune system responses and behavioral abnormalities in male mice

Recent evidence indicates the involvement of inflammatory factors and mitochondrial dysfunction in the etiology of psychiatric disorders such as anxiety and depression. To investigate the possible role of mitochondrial-induced sterile inflammation in the co-occurrence of anxiety and depression, in this study, we treated adult male mice with the intracerebroventricular (i.c.v.) infusion of a single low dose of streptozotocin (STZ, 0.2 mg/mouse). Using valid and qualified behavioral tests for the assessment of depressive and anxiety-like behaviors, we showed that STZ-treated mice exhibited behaviors relevant to anxiety and depression 24 h following STZ treatment. We observed that the co-occurrence of anxiety and depressive-like behaviors in animals were associated with abnormal mitochondrial function, nitric oxide overproduction and, the increased activity of cytosolic phospholipase A2 (cPLA2) in the hippocampus. Further, STZ-treated mice had a significant upregulation of genes associated with the innate immune system such as toll-like receptors 2 and 4. Pathological evaluations showed no sign of neurodegeneration in the hippocampus of STZ-treated mice. Results of this study revealed that behavioral abnormalities provoked by STZ, as a cytotoxic agent that targets mitochondria and energy metabolism, are associated with abnormal mitochondrial activity and, consequently the initiation of innate-inflammatory responses in the hippocampus. Our findings highlight the role of mitochondria and innate immunity in the formation of sterile inflammation and behaviors relevant to anxiety and depression. Also, we have shown that STZ injection (i.c.v.) might be an animal model for depression and anxiety disorders based on sterile inflammation

Luteolin Reduced the Traumatic Brain Injury-Induced Memory Impairments in Rats: Attenuating Oxidative Stress and Dark Neurons of Hippocampus

Traumatic Brain Injury (TBI) is generally recognized as a major risk factor for memory impairments and Alzheimer’s disease (AD). In this experimental study, our aim was to investigate the ameliorating effects of luteolin (LUT) on the memory impairments, oxidative stress, and histopathological changes induced by TBI in rats. The adult male Wistar rats were randomly divided into six groups including: Control (Co), sham, TBI, TBI+LUT (10 mg/kg), TBI +LUT (25 mg/kg), TBI +LUT (50 mg/kg). To evaluate the protective effects of LUT on the memory of the rats, passive avoidance test using shuttle box was performed. Finally, the animals were anesthetized, and the brain tissues were removed and analyzed for oxidative stress parameters. Using histological methods, dark neuron production was also evaluated. There was a significant decrease in the latency time to enter the dark compartment in passive avoidance test in TBI animals. This latency time was significantly increased in TBI+LUT (25 mg/kg) and TBI+LUT (50 mg/kg) groups along with significant increases in superoxide dismutase and catalase activity in the hippocampal zone and a decrease in malondialdehyde (MDA). The number of dark neurons in the hippocampus decreased with all three doses of LUT. In the present study, LUT showed neuroprotective effects, improvement in learning and reduction in memory impairment induced by TBI in rats. Protection against oxidative stress might be a possible mechanism behind these effects. Further works are necessary to work out if LUT is potentially a suitable therapeutic candidate for neural disorders

Effects of melatonin on neuropathic pain-induced mood disorders and its anti-inflammatory and anti-apoptotic mechanisms

背景：神经病理痛（NP）作为一种疼痛综合征，具有多种不同的临床表现，如异常性疼痛、痛觉过敏、自发性疼痛和多种感觉的异常。其中，高达 80% 的慢性疼痛患者还并发有有精神疾病，例如抑郁症和焦虑症。 NP被认为是一种慢性疾病，通常伴有情绪变化。含有核因子-B (NF-B)/NLR 家族 pyrin 结构域 3 (NLRP3) 轴在将应激反应转化为免疫系统反应方面发挥重要作用。相关研究发现，神经病理痛模型下，情绪调节的相关脑区中出现了神经炎症和细胞凋亡。最近的研究表明，具有抗氧化和抗炎特性的褪黑激素（MLT）可用于预防和治疗神经系统疾病。在本研究中，我们评估了褪黑激素对大鼠神经病理痛模型诱导的情感障碍（即焦虑和抑郁）的调节作用，以及其对相应脑区内细胞的抗凋亡和抗炎作用。 方法：成年雄性大鼠分为四组(n=13)，包括假手术组、褪黑素组（MLT）：即腹腔注射MLT（10mg/kg）， 慢性坐骨神经结扎组（CCI）：坐骨神经结扎术后+腹腔注射溶剂对照，以及CCI+MLT组：CCI术后两周给与褪黑激素。接下来，我们使用行为测试来评估疼痛感觉，焦虑和抑郁的严重程度。最后，对大鼠进行分子和组织病理学研究。 其中从以下方面探究了MLT所起的作用：1) 在第 0 天（手术前）、3、7、14 和 21 天通过热板试验 (HPT) 和丙酮滴试验 (ADT) 评估疼痛严重程度，2) 在第 22 至 26 天通过高架十字迷宫试验 (EPMT)，强迫游泳试验 (FST)、悬尾试验 (TST) 和旷场试验 (OFT) 评估焦虑和抑郁，3) 评估 NF-κB/NLRP3 轴成分，包括 NF-κB、NLRP3、以及凋亡相关蛋白，如 CARD (ASC) 和 Caspase-1 的激活程度，4) 细胞因子，包括白细胞介素 1 β (IL-1β) 和 IL-18，以及 5) 细胞凋亡和凋亡调节介质（Bax 和 Bcl2）在 前额叶皮层（PFC）和海马体（HC）的表达含量。 结果：行为测试显示，NP模型大鼠出现了情绪异常。 NP 通过上调 NF-ᴋB、NLRP3、ASC 和活性 Caspase-1 并提高前额叶皮层 (PFC) 和海马 (HC) 中细胞因子（IL1β 和 IL-18）的浓度来激活 NF-κB/NLRP3 炎性体通路。慢性疼痛条件下， Bax（促凋亡蛋白）被显著上调， Bcl2（抗凋亡蛋白）被显著下调，从而加速HC 和 PFC 中的细胞凋亡。 MLT 治疗显著消除了 NP 的影响，表现为疼痛严重程度降低、情感障碍改善、NF-κB-NLRP3 炎性体通路正常化以及调节了HC 和 PFC 中细胞凋亡相关的细胞因子水平，即MLT 可通过逆转 Bax和 Bcl2的表达水平的异常，抑制细胞凋亡。 结论：我们的研究结果表明，动物暴露于慢性 NP 通过激活 NF-κB/NLRP3 轴和 HC 和 PFC 中凋亡调节介质的失调来诱导情绪改变。 MLT 对NP 诱导的焦虑和抑郁样行为中的挽救作用可能是由其抗凋亡和抗炎特性介导的

Exogenous melatonin alleviates neuropathic pain-induced affective disorders by suppressing NF-kappaB/ NLRP3 pathway and apoptosis.

In this study, we aimed to evaluate the anti-inflammatory and anti-apoptotic effects of melatonin (MLT) on neuropathic pain (NP)-induced anxiety and depression in a rat model. Adult male rats were separated into four groups, i.e., Sham-VEH: healthy animals received a vehicle, Sham-MLT (10mg/kg), and chronic constrictive injury (CCI)-VEH: nerve ligation received the vehicle, and CCI-MLT. Next, we used behavioral tests to evaluate pain severity, anxiety, and depression. Finally, rats were sacrificed for molecular and histopathological studies. Behavioral tests showed that NP could induce depressive- and anxiety-like behaviors. NP activated NF-kappaB/NLRP3 inflammasome pathways by upregulating NF-kappaB, NLRP3, ASC, active Caspase-1, also enhancing the concentrations of cytokines (IL-1beta and IL-18) in the prefrontal cortex (PFC) and hippocampus (HC). NP upregulated Bax, downregulated Bcl2, and increased cell apoptosis in the HC and PFC. The rats treated with MLT eliminated the effects of NP, as the reduced pain severity, improved anxiety- and depressive-like behaviors, ameliorated NF-kappaB/NLRP3 inflammasome pathways, and modulated levels of cytokines in the HC and PFC. MLT could promote cell survival from apoptosis by modulating Bax and Bcl2. Therefore, it might be inferred that its anti-inflammatory and anti-apoptotic properties mediate the beneficial effects of MLT in NP-induced affective disorders.</p