Search results for: endothelial dysfunction

Authors: Sadia Munir

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Preeclampsia is the contributor to the worldwide maternal mortality of approximately 100,000 deaths a year. It complicates about 10% of all pregnancies and is the first cause of maternal admission to intensive care units. Predicting preeclampsia is a major challenge in obstetrics. More importantly, no major progress has been achieved in the treatment of preeclampsia. As placenta is the main cause of the disease, the only way to treat the disease is to extract placental and deliver the baby. In developed countries, the cost of an average case of preeclampsia is estimated at £9000. Interestingly, preeclampsia may have an impact on the health of mother or infant, beyond the pregnancy. We performed a systematic search of PubMed including the combination of terms such as preeclampsia, biomarkers, treatment, hypoxia, inflammation, oxidative stress, vascular endothelial growth factor A, activin A, inhibin A, placental growth factor, transforming growth factor β-1, Nodal, placenta, trophoblast cells, microRNAs. In this review, we have summarized current knowledge on the identification of potential biomarkers for the diagnosis of preeclampsia. Although these studies show promising data in early diagnosis of preeclampsia, the current value of these factors as biomarkers, for the precise prediction of preeclampsia, has its limitation. Therefore, future studies need to be done to support some of the very promising and interesting data to develop affordable and widely available tests for early detection and treatment of preeclampsia.

Keywords: activin, biomarkers, growth factors, miroRNA

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Authors: Behnam Shakerian, Negin Razavi

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The pathogenesis of coronary artery disease is multifactorial. The epicardial fat pad is a localized fat depot lying between the myocardium and the visceral layer of the pericardium. The mechanisms through which epicardial fat pad can cause atherosclerosis are complex. The epicardial fat pad can surround the coronary arteries and contributes to the development and progression of coronary artery disease. Methods: we selected 50 patients who underwent coronary artery angiography for the evaluation of coronary artery disease that results were positive for coronary artery disease. All patients underwent an echocardiographic examination after coronary angiography to measure epicardial fat pad thickness. The epicardial fat pad was defined as an echo-free space between the myocardium's outer wall and the pericardium's visceral layer. Results: The epicardial fat pad was measured on the right ventricle apex in 46 patients. Sixty- five percent of the studied patients were male. The most common vessel with stenosis was the left anterior descending artery. A significant correlation was observed between epicardial fat pad thickness and the severity of coronary artery disease. Discussions: The epicardial fat pad provides a horizon on the pathophysiology of cardiovascular diseases. It directly contributes to the development and progression of coronary artery disease by causing inflammation and endothelial damage. Further investigations are needed to determine whether medical treatment can reduce the mass of epicardial fat pad and can help to improve atherosclerosis. Conclusion: The epicardial fat pad measurement could be used as an indicator of coronary arteries’ atherosclerosis. Therefore, thickness measurement of the epicardial fat pad in the clinical practice could be of assistance in identifying patients at risk and if required, undergoing supplementary diagnosis with coronary angiography.

Keywords: epicardial, fat pad, coronary artery disease, echocardiography

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Authors: David J. Thomson, Joshua C. J. Chew

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Background: Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) is a rare complication of lithium toxicity that typically causes irreversible cerebellar dysfunction. These patients may require hemodialysis and extensive supports in the intensive care. Methods: A review was performed on the available literature of SILENT with a focus on current pathophysiological hypotheses and advances in treatment. Articles were restricted to the English language. Results: Although the exact mechanism is unclear, CNS demyelination, especially in the cerebellum, was seen on the brain biopsies of a proportion of patients. There is no definitive management of SILENT but instead current management is focused on primary and tertiary prevention – detection of those at risk, and rehabilitation post onset of neurological deficits. Conclusions: This review draws conclusions from a limited amount of available literature, most of which are isolated case reports. Greater awareness of SILENT and further investigation into the risk factors and pathogenesis are required so this serious and irreversible syndrome may be avoided.

Keywords: lithium toxicity, pathogenesis, SILENT, syndrome of irreversible lithium-effectuated neurotoxicity

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Authors: S. B. R. Slagmulder

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Monitoring inspiratory effort and dynamic lung stress in patients on pressure support ventilation in the ICU is important for protecting against self inflicted lung injury (P-SILI) and diaphragm dysfunction. Strategies to address the detrimental effects of respiratory drive and effort can lead to improved patient outcomes. Two non-invasive estimation methods, occlusion pressure (Pocc) and P0.1, have been proposed for achieving lung and diaphragm protective ventilation. However, their relationship and interpretation in neuro ICU patients is not well understood. P0.1 is the airway pressure measured during a 100-millisecond occlusion of the inspiratory port. It reflects the neural drive from the respiratory centers to the diaphragm and respiratory muscles, indicating the patient's respiratory drive during the initiation of each breath. Occlusion pressure, measured during a brief inspiratory pause against a closed airway, provides information about the inspiratory muscles' strength and the system's total resistance and compliance. Research Objective: Understanding the relationship between Pocc and P0.1 in brain-injured patients can provide insights into the interpretation of these values in pressure support ventilation. This knowledge can contribute to determining extubation readiness and optimizing ventilation strategies to improve patient outcomes. The central goal is to asses a study protocol for determining the relationship between Pocc and P0.1 in brain-injured patients on pressure support ventilation and their ability to predict successful extubation. Additionally, comparing these values between brain-damaged and non-brain-damaged patients may provide valuable insights. Key Areas of Inquiry: 1. How do Pocc and P0.1 values correlate within brain injury patients undergoing pressure support ventilation? 2. To what extent can Pocc and P0.1 values serve as predictive indicators for successful extubation in patients with brain injuries? 3. What differentiates the Pocc and P0.1 values between patients with brain injuries and those without? Methodology: P0.1 and occlusion pressures are standard measurements for pressure support ventilation patients, taken by attending doctors as per protocol. We utilize electronic patient records for existing data. Unpaired T-test will be conducted to compare P0.1 and Pocc values between both study groups. Associations between P0.1 and Pocc and other study variables, such as extubation, will be explored with simple regression and correlation analysis. Depending on how the data evolve, subgroup analysis will be performed for patients with and without extubation failure. Results: While it is anticipated that neuro patients may exhibit high respiratory drive, the linkage between such elevation, quantified by P0.1, and successful extubation remains unknown The analysis will focus on determining the ability of these values to predict successful extubation and their potential impact on ventilation strategies. Conclusion: Further research is pending to fully understand the potential of these indices and their impact on mechanical ventilation in different patient populations and clinical scenarios. Understanding these relationships can aid in determining extubation readiness and tailoring ventilation strategies to improve patient outcomes in this specific patient population. Additionally, it is vital to account for the influence of sedatives, neurological scores, and BMI on respiratory drive and occlusion pressures to ensure a comprehensive analysis.

Keywords: brain damage, diaphragm dysfunction, occlusion pressure, p0.1, respiratory drive

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Authors: Negin Parsamanesh, Saman Ameri-Mahabadi, Ali Nikfar, Mojdeh Mansouri, Hossein Chiti, Gita Fatemi Abhari

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Duchenne muscular dystrophy (DMD) is a severe progressive X-linked neuromuscular illness that affects movement through mutations in dystrophin gene. The mutation leads to insufficient, lack of or dysfunction of dystrophin. The cause of DMD was determined in an Iranian family. Exome sequencing was carried out along with a complete physical examination of the family. In silico methods were applied to find the alteration in the protein structure. The homozygous variant in DMD gene (NM-004006.2) was defined as c.2732-2733delTT (p.Phe911CysfsX8) in exon 21. In addition, phylogenetic conservation study of the human dystrophin protein sequence revealed that phenylalanine 911 is one of the evolutionarily conserved amino acids. In conclusion, our study indicated a new deletion in the DMD gene in the affected family. This deletion with an X-linked inheritance pattern is new in Iran. These findings could facilitate genetic counseling for this family and other patients in the future.

Keywords: duchenne muscular dystrophy, whole exome sequencing, iran, metabolic syndrome

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Authors: Teresa Rushe, Nicole Devlin, Tara O Neill

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In this study, we sought to examine associations between childhood experiences of community and collective violence and psychological functioning in young people who grew up in post-conflict Northern Ireland. We hypothesized that those who grew up with such experiences would demonstrate internalizing and externalizing difficulties in early adulthood and, furthermore, that these difficulties would be mediated by adverse childhood experiences occurring within the home environment. As part of the Northern Ireland Childhood Adversity Study, we recruited 213 young people aged 18-25 years (108 males) who grew up in the post-conflict society of Northern Ireland using purposive sampling. Participants completed a digital questionnaire to measure adverse childhood experiences as well as aspects of psychological functioning. We employed the Adverse Childhood Experience -International Questionnaire (ACE-IQ¬) adaptation of the original Adverse Childhood Experiences Questionnaire (ACE) as it additionally measured aspects of witnessing community violence (e.g., seeing someone being beaten/killed, fights) and experiences of collective violence (e.g., war, terrorism, police, or gangs’ battles exposure) during the first 18 years of life. 51% of our sample reported experiences of community and/or collective violence (N=108). Compared to young people with no such experiences (N=105), they also reported significantly more adverse experiences indicative of household dysfunction (e.g., family substance misuse, mental illness or domestic violence in the family, incarceration of a family member) but not more experiences of abuse or neglect. As expected, young people who grew up with the community and/or collective violence reported significantly higher anxiety and depression scores and were more likely to engage in acts of deliberate self-harm (internalizing symptoms). They also started drinking and taking drugs at a younger age and were significantly more likely to have been in trouble with the police (externalizing symptoms). When the type of violence exposure was separated by whether the violence was witnessed (community violence) or more directly experienced (collective violence), we found community and collective violence to have similar effects on externalizing symptoms, but for internalizing symptoms, we found evidence of a differential effect. Collective violence was associated with depressive symptoms, whereas witnessing community violence was associated with anxiety-type symptoms and deliberate self-harm. However, when experiences of household dysfunction were entered into the models predicting anxiety, depression, and deliberate self-harm, none of the main effects remained significant. This suggests internalizing type symptoms are mediated by immediate family-level experiences. By contrast, significant community and collective violence effects on externalizing behaviours: younger initiation of alcohol use, younger initiation of drug use, and getting into trouble with the police persisted after controlling for family-level factors and thus are directly associated with growing up with the community and collective violence. Given the cross-sectional nature of our study, we cannot comment on the direction of the effect. However, post-hoc correlational analyses revealed associations between externalising behaviours and personal factors, including greater risk-taking and young age at puberty. The implications of the findings will be discussed in relation to interventions for young people and families living with the community and collective violence.

Keywords: community and collective violence, adverse childhood experiences, youth, psychological wellbeing

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Authors: Armaghan Moravej Aleali, Seyed Bahman Ghaderian, Homeira Rashidi, Mahmoud Mapar

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Background and Objective The metabolic syndrome (MetS) is considered the most important public health threat of the 21st century. This syndrome is characterized by a cluster of cardiovascular risk factors including increased central abdominal obesity, elevated triglycerides, reduced high-density lipoprotein, high blood pressure, increased fasting glucose, and hyperinsulinemia. MetS has been associated with hypogonadism and erectile dysfunction (ED), and MetS may be considered a risk factor for ED. The aim of this study was finding an association between metabolic syndrome and hypogonadism in Khouzestan, Iran. Subjects and Methods: In this study, 60 patients divided into two groups consisted of 30 cases (with metabolic syndrome) and 30 controls. Total and free Serum Testosterone and FBS in all of them were measured. Data was analyzed with SPSS20 program. Results: There was a significant difference between two groups about free Testosterone (P=0.01), FBS (P=0.002) and LH (P=0.03). Conclusion: According to this finding, it is thought the prevalence of hypogonadism in men with metabolic syndrome is more than the general population.

Keywords: metabolic syndrome, fasting blood sugar, hypogonadism, testosterone

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Authors: Avigail Moor

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A decline in women’s sexual desire over the course of long-term relationships, relative to men’s, has been frequently noted. Yet, while there is ample evidence that this change in women is quite common, it is still generally pathologized. Moreover, little is known regarding its true meaning for women and the effect it has on their wellbeing. In light of that, our primary goal was to investigate women's subjective experiences of this reality. Do they connect it to dysfunction in self or marriage, or rather they don't equate love and sex, which for them simply become less connected with time, even as the relationship remains entirely fulfilling? A second goal was to explore how such gender-based differences in sexual desire impact women, and indirectly the couple and partner, in terms of wellbeing and satisfaction from the relationship. In-depth semi-structured interviews were conducted with 15 women in committed long-term relations, aged 25 and over. The findings indicate that for women, there is no contradiction between a loving relation and a decline in spontaneous sexual desire. At the same time, while not rooted in a problem, it does create some. Tension, frustration, conflict, and pressure are some of the negative sequelae that carry adverse effects for women’s wellbeing, the solution to which requires, in their opinion, honest dialogue, mutual respect, and reasonable compromise.

Keywords: gender, sexuality, sexual desire, well being

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Authors: Sujata Chaturvedi, Ishita Pant, Deepak Kumar Jha, Vinod Kumar Singh Gautam, Chandra Bhushan Tripathi

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Objective: To describe clinical, histopathological and immunohistochemical profile of glioblastoma in patients and to correlate these findings with patient survival. Material and methods: 30 cases of histopathologically diagnosed glioblastomas were included in this study. These cases were analysed in detail for certain clinical and histopathological parameters. Immunohistochemical staining for p53, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), mouse double minute 2 homolog (MDM2) and Ki67 was done and scores were calculated. Results of these findings were correlated with patient survival. Results: A retrospective analysis of the histopathology records and clinical case files was done in 30 cases of glioblastoma (WHO grade IV). The mean age of presentation was 50.6 years with a male predilection. The most common involved site was the frontal lobe. Amongst the clinical parameters, age of the patient and extent of surgical resection showed a significant correlation with the patient survival. Histopathological parameters showed no significant correlation with the patient survival, while amongst the immunohistochemical parameters expression of MDM2 showed a significant correlation with the patient survival. Conclusion: In this study incorporating clinical, histopathological and basic panel of immunohistochemistry, age of the patient, extent of the surgical resection and expression of MDM2 showed significant correlation with the patient survival.

Keywords: glioblastoma, p53, EGFR, VEGF, MDM2, Ki67

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Authors: Suphaket Saenthaweesuk, Nutiya Somparn, Atcharaporn Thewmore

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The present study aims to investigate the effects of Cymbopogon citratus, Stapf (CS) or lemon grass ethanol extract on antioxidant and vascular disorders parameters in rat. The CS ethanol extract was screened for its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Rats were orally administered with CS at 1,000 mg/kg/day for 30 days. Phytochemical screening of CS extract indicated the presence of tannins, flavonoids and phenolic compounds. The extract contained phenolic compounds 1,400.10 ± 0.47 mg of gallic acid equivalents per gram CS extract. The free radical scavenging activity assessed by DPPH assay gave IC50 of 168.77 ± 3.32µg/mL, which is relatively lower than that of BHT with IC50 of 12.34 ± 1.14 µg/mL. In the animals, the protein expression of antioxidant enzymes, γ-glutamylcysteine ligase (γ-GCL) in liver was significantly increased. This was consistent with elevation of serum catalase (CAT) and superoxide dismutase (SOD) activities. However, Protein expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial nitric oxide synthase (eNOS) in heart and aorta were not differenced from normal control. Taken together, the present study provides evidence that CCS water extract exhibits direct antioxidant properties and can induce cytoprotective enzymes in vivo.

Keywords: antioxidant, Cymbopogon citratus Stapf, VCAM-1, γ-glutamylcysteine ligase

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Authors: Vinay Kumar Theendra

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The main objective of the study is to evaluate the effectiveness of hesperidin in the treatment of breast cancer and causing less (or) no bone marrow depression which is the major side effect of the present anticancer drugs treating breast cancer, also to evaluate the mechanisms through which these compounds are exerting their effect. Breast cancer is induced by administering N-methyl N-Nitrosourea (MNU) at a dose of 50mg/kg body weight. Upon the termination of the experiment, the animals were sacrificed by the method of cervical dislocation. The animals were dissected along the ventral midline and were grossly examined for the presence of tumors. Then the tumours were removed along with the stroma. Vascular endothelial growth factor (VEGF) levels were estimated by using ELISA method. The first occurrence of palpable tumors was eight weeks after carcinogen treatment and the final tumour incidence was 100% in the MNU alone and topical treated rats. Whereas in rats of other treatment groups there is decreased tumour incidence which might be due to their antitumour activity. Hesperidin therapy inhibited angiogenesis which can be evident from the significant reduction in serum as well as tumour VEGF concentrations in comparison to the untreated mammary carcinoma bearing rats. Hesperidin is promising agents that exert direct antitumor and also antiangiogenic, antiproliferative and anti-inflammatory activities. Even though the potency is little lesser than standard drug vincristine, it has been proved to be safe without effecting haematological count.

Keywords: hesperidin, VEGF, COX 2, N-methyl N-nitrosourea

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Authors: Loubna Safar, Lama Youssef, Majd Aljamali

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Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide. Complement factor H polymorphism (Y402H) is thought to play a potential role in the predisposition to AMD and response of patients with exudative AMD to treatment with anti-Vascular Endothelial Growth Factor (anti-VEGF). This study aimed to investigate the frequency of Y402H among Syrians, its impact on their susceptibility to AMD, and the hypothesized role of Y402H in patients' response to intravitreal anti-VEGF (i.e.,, bevacizumab). Our case-control study encompassed unrelated 54 AMD cases and 44 controls. Genotyping was determined by standard sequencing of PCR products. Frequency was compared between patients and controls, and correlation between genotype and response to treatment was assessed in 20 patients with wet AMD who received a therapeutic course of three intravitreal bevacizumab injections (once monthly). Our results revealed a significantly higher prevalence of the risk allele C among AMD cases (51.9%) in comparison with controls (37.5%) (P= 0.04, OR= 1.386, CI= 0.999- 1.923). Patients with the TT genotype (no risk allele) exhibited a significantly better primary response rate, reached 87.5% compared to only 41.7% in patients carrying the risk allele C (TC + CC), (P= 0.04, OR= 9.8, CI=0.899- 106.84). The findings of this study prove the importance of investigating Y402H polymorphism as a prognostic marker for predicting response to bevacizumab in AMD patients.

Keywords: age-related macular degeneration, bevacizumab, complement factor H gene, polymorphism, Y402H

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Authors: Selena Ferrian, Erin Mccaffrey, Toshie Saito, Aiqin Cao, Noah Greenwald, Mark Robert Nicolls, Trevor Bruce, Roham T. Zamanian, Patricia Del Rosario, Marlene Rabinovitch, Michael Angelo

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Recent experimental and clinical observations are advancing immunotherapies to clinical trials in pulmonary arterial hypertension (PAH). However, comprehensive mapping of the immune landscape in pulmonary arteries (PAs) is necessary to understand how immune cell subsets interact to induce pulmonary vascular pathology. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to interrogate the immune landscape in PAs from idiopathic (IPAH) and hereditary (HPAH) PAH patients. Massive immune infiltration in I/HPAH was observed with intramural infiltration linked to PA occlusive changes. The spatial context of CD11c+DCs expressing SAMHD1, TIM-3 and IDO-1 within immune-enriched microenvironments and neutrophils were associated with greater immune activation in HPAH. Furthermore, CD11c-DC3s (mo-DC-like cells) within a smooth muscle cell (SMC) enriched microenvironment were linked to vessel score, proliferating SMCs, and inflamed endothelial cells. Experimental data in cultured cells reinforced a causal relationship between neutrophils and mo-DCs in mediating pulmonary arterial SMC proliferation. These findings merit consideration in developing effective immunotherapies for PAH.

Keywords: pulmonary arterial hypertension, vascular remodeling, indoleamine 2-3-dioxygenase 1 (IDO-1), neutrophils, monocyte-derived dendritic cells, BMPR2 mutation, interferon gamma (IFN-γ)

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Authors: Sehur Sibel Ozkaynak, Zakir Koc, Ebru Barcın

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Essential tremor (ET) is one of the most common movement disorders and has long been considered a monosymptomatic disorder. While ET has traditionally been categorized as a pure motor disease, cross-sectional and longitudinal studies of cognition in ET have been demonstrated that these patients may have cognitive dysfunction. We investigated the neuro physiological aspects of cognition in ET, using event-related potentials (ERPs).Twenty patients with ET and 20 age-education and sex matched healthy controls underwent a neuro physiological evaluation. P300 components and Contingent Negative Variation (CNV) were recorded. The latencies and amplitudes of the P300 and CNV were evaluated. P200-N200 amplitude was significantly smaller in the ET group, while no differences emerged between patients and controls in P300 latencies. CNV amplitude was significantly smaller at Cz electrode site in the ET group. No differences were observed between in the two groups in CNV latencies. As a result, P300 and CNV parameters did not show significant differences between in the two groups, does not mean that there aren't mild cognitive changes in ET patients. In this regard, there is a need to further studies using electro physiological tests related to cognitive changes in ET patients.

Keywords: cognition, essential tremor, event related potentials

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Authors: Uma Kanth, Amy Cook

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Conceptual Metaphor Theory (CMT) proposes that metaphor is fundamental to human thought. CMT utilizes embodied cognition, in that emotions are conceptualized as effects on the body because of a coupling of one’s bodily experiences and one’s somatosensory system. Time perception is a function of embodied cognition and conceptual metaphor in that one’s experience of time is inextricably dependent on one’s perception of the world around them. A hallmark of depressive disorders is the distortion in one’s perception of time, such as neurological dysfunction and psychomotor retardation, and yet, to the author’s best knowledge, previous studies have not before linked CMT, embodied cognition, and depressive disorders. Therefore, the focus of this paper is the investigation of how the applications of CMT and embodied cognition (especially regarding time perception) have promise in improving current techniques to treat depressive disorders. This paper aimed to extend, through a thorough review of literature, the theoretical basis required to further research into CMT and embodied cognition’s application in treating time distortion related symptoms of depressive disorders. Future research could include the development of brain training technologies that capitalize on the principles of CMT, with the aim of promoting cognitive remediation and cognitive activation to mitigate symptoms of depressive disorder.

Keywords: depression, conceptual metaphor theory, embodied cognition, time

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Authors: Jung Park, Anca Mazare, Klaus Von Der Mark, Patrik Schmuki

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In clinical application of TiO2 implants on tooth and hip replacement, migration, adhesion and differentiation of neighboring mesenchymal stem cells onto implant surfaces are critical steps for successful bone regeneration. In a recent decade, accumulated attention has been paid on nanoscale electrochemical surface modifications on TiO2 layer for improving bone-TiO2 surface integration. We generated, on titanium surfaces, self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm and here we show that mesenchymal stem cells finely sense TiO2 nanotubular geometry and quickly decide their cell fate either to differentiation into osteoblasts or to programmed cell death (apoptosis) on TiO2 nanotube layers. These cell fate decisions are critically dependent on nanotube size differences (15-100nm in diameters) of TiO2 nanotubes sensing by integrin clustering. We further demonstrate that nanoscale topography-sensing is feasible not only in mesenchymal stem cells but rather seems as generalized nanoscale microenvironment-cell interaction mechanism in several cell types composing bone tissue network including osteoblasts, osteoclast, endothelial cells and hematopoietic stem cells. Additionally we discuss the synergistic effect of simultaneous stimulation by nanotube-bound growth factor and nanoscale topographic cues on enhanced bone regeneration.

Keywords: TiO2 nanotube, stem cell fate decision, nano-scale microenvironment, bone regeneration

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Authors: James Pietris

Abstract:

Glaucoma is a collection of irreversible optic neuropathies which, if left untreated, lead to severe visual field loss. These diseases are a leading cause of blindness across the globe and are estimated to affect approximately 80 million people, particularly women and people of Asian descent.1This represents a major burden on healthcare systems worldwide. Recently, there has been increasing interest in the potential of nicotinamide (vitamin B3) as a novel option in the management of glaucoma. This review aims to analyse the currently available literature to determine whether there is evidence of an association between nicotinamide adenine dinucleotide (NAD+) and glaucomatous optic neuropathy and whether nicotinamide has the potential to prevent or reverse these effects. The literature showed a strong connection between reduced NAD+ levels and retinal ganglion cell dysfunction through multiple different studies. There is also evidence of the positive effect of nicotinamide supplementation on retinal ganglion cell function in models of mouse glaucoma and in a study involving humans. Based on the literature findings, a recommendation has been made that more research into the efficacy, appropriate dosing, and potential side effects of nicotinamide supplementation is needed before it can be definitively determined whether it is appropriate for widespread prophylactic and therapeutic use against glaucoma in humans.

Keywords: glaucoma, nicotinamide, vitamin B3, optic neuropathy

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Authors: Silvia Di Giacomo, Marcello Locatelli, Simone Carradori, Francesco Cacciagrano, Chiara Toniolo, Gabriela Mazzanti, Luisa Mannina, Stefania Cesa, Antonella Di Sotto

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Hyperglycemia represents the main pathogenic factor in the development of diabetes complications and has been found associated with mitochondrial dysfunction and oxidative stress, which in turn increase cell dysfunction. Therefore, counteract oxidative species appears to be a suitable strategy for preventing the hyperglycemia-induce cell damage and support the pharmacotherapy of diabetes and metabolic diseases. Antidiabetic potential of many food sources has been linked to the presence of polyphenolic metabolites, particularly flavonoids such as quercetin and its glycosylated form rutin. In line with this evidence, in the present study, we assayed the potential anti-hyperglycemic activity of an ethyl acetate extract from the peel of Punica granatum L. var. Dente di Cavallo (PGE), a fruit well known to traditional medicine for the beneficial properties of its edible juice. The effect of the extract on the glucidic metabolism has been evaluated by assessing its ability to inhibit α-amylase and α-glucosidase, two digestive enzymes responsible for the hydrolysis of dietary carbohydrates: their inhibition can delay the carbohydrate digestion and reduce glucose absorption, thus representing an important strategy for the management of hyperglycemia. Also, the PGE ability to block the release of advanced glycated end-products (AGEs), whose accumulation is known to be responsible for diabetic vascular complications, was studied. The iron-reducing and chelating activities, which are the primary mechanisms by which AGE inhibitors stop their metal-catalyzed formation, were evaluated as possible antioxidant mechanisms. At last, the phenolic content of PGE was characterized by chromatographic and spectrophotometric methods. Our results displayed the ability of PGE to inhibit α-amylase enzyme with a similar potency to the positive control: the IC₅₀ values were 52.2 (CL 27.7 - 101.2) µg/ml and 35.6 (CL 22.8 - 55.5) µg/ml for acarbose and PGE, respectively. PGE also inhibited the α-glucosidase enzyme with about a 25 higher potency than the positive controls of acarbose and quercetin. Furthermore, the extract exhibited ferrous and ferric ion chelating ability, with a maximum effect of 82.1% and 80.6% at a concentration of 250 µg/ml respectively, and reducing properties, reaching the maximum effect of 80.5% at a concentration of 10 µg/ml. At last, PGE was found able to inhibit the AGE production (maximum inhibition of 82.2% at the concentration of 1000 µg/ml), although with lower potency with respect to the positive control rutin. The phytochemical analysis of PGE displayed the presence of high levels of total polyphenols, tannins, and flavonoids, among which ellagic acid, gallic acid and catechin were identified. Altogether these data highlight the ability of PGE to control the carbohydrate metabolism at different levels, both by inhibiting the metabolic enzymes and by affecting the AGE formation likely by chelating mechanisms. It is also noteworthy that peel from pomegranate, although being a waste of juice production, can be reviewed as a nutraceutical source. In conclusion, present results suggest the possible role of PGE as a remedy for preventing hyperglycemia complications and encourage further in vivo studies.

Keywords: anti-hyperglycemic activity, antioxidant properties, nutraceuticals, polyphenols, pomegranate

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Authors: Jeonghun Lee

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In this study, we investigated the relationship between stress and thyroid dysfunction in such patients who underwent thyroidectomy. This study included 101 patients who underwent thyroidectomy from January 2015 to June 2020 and experienced hypothyroidism. The included patients had good drug compliance with the same dosage of levothyroxine (LT4). The male-to-female ratio was 1:4.6, and the mean age was 45.4 years at surgery and 50.2 years at stressful events. Eighteen patients underwent lobectomies and, of these, 12 did not take LT4. The mean follow-up period was 49(8-93) months. Statistical analyses were performed using the paired t-test, Wilcoxon signed-rank test, and McNemer test using PROC MIXED with SAS 9.4. Forty-five patients (44.6%) had hypothyroidism with thyroid-stimulating hormone (TSH) >10 μIU/mL. There was distress in 81 patients and eustress in 10 patients. TSH levels increased during a mean 5.8 months (min 1, max 12) in 24 patients who specified the date of their life events. Even though each patient took the same dose of LT4, when the patients were under stress, both the free T4 and T3 decreased and TSH increased, regardless of whether the patient experienced distress or eustress (P <0.001). While adjusting for the effect of the free T4 and T3, TSH increased significantly in the patients after stress (P <0.001). For patients with thyroid cancer who are simultaneously experiencing life events, TSH may be used as a stress biomarker to enable the implementation of appropriate treatment and counseling strategies.

Keywords: endocrine, thyroid, thyroid function, biomarker, stress

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Hamid Reza Khodaei, Behnaz Mahdavi, Alireza Banitaba

Abstract:

Nitric oxide (NO) plays an important role in all sexual activities of animals. It is made in body from NO syntheses enzyme and L-arginin molecule. NO can make band with sulfur-iron complexes and due to production of steroid sexual hormones related to enzymes which have this complex, NO can change the activity of these enzymes. NO affects many cells including endothelial cells of veins, macrophages and mast cells. These cells are found in testis leydig cells and therefore are important source of NO in testis tissue. Minimizing damages to sperm at the time of sperm freezing and thawing is really important. The goal of this study was to determine the function of NO before freezing and its effects on quality and viability of sperms after thawing and incubation. 4 Holstein bulls were selected from the age of 4, and artificial insemination was done for 3 weeks (2 times a week). Treatments were 0, 10, 50 and 100 nm of sodium nitroprusside (SNP). Data analysis was performed by SAS98 program. Also, mean comparison was done using Duncan's multiple ranges test (P<0.05). Concentrations used were found to increase motility and viability of spermatozoa at 1, 2 and 3 hours after thawing significantly (P<0.05) but there was no significant difference at zero time. SNP levels reduced the amount of lipid peroxidation in sperm membrane, increased acrosome health and improved samples membranes especially in 50 and 100 nm treatments. According to results, adding SNP to semen diluents increases motility and viability of spermatozoa. Also, it reduces lipid peroxidation in sperm membrane and improves sperm function.

Keywords: sperm motility, nitric oxide, lipid peroxidation, spermatozoa

Procedia PDF Downloads 621

Authors: Kartik Gupta, Virendra Kumar, Sanjeev Sinha, N. Jagannathan

Abstract:

Introduction: A significant number of patients having human immunodeficiency virus (HIV) infection show a neurocognitive decline (NCD) ranging from minor cognitive impairment to severe dementia. The possible causes of NCD in HIV-infected patients include brain injury by HIV before cART, neurotoxic viral proteins and metabolic abnormalities. In the present study, we compared the level of NCD in asymptomatic HIV-infected patients with changes in brain metabolites measured by using magnetic resonance spectroscopy (MRS). Methods: 43 HIV-positive patients (30 males and 13 females) coming to ART center of the hospital and HIV-seronegative healthy subjects were recruited for the study. All the participants completed MRI and MRS examination, detailed clinical assessments and a battery of neuropsychological tests. All the MR investigations were carried out at 3.0T MRI scanner (Ingenia/Achieva, Philips, Netherlands). MRI examination protocol included the acquisition of T2-weighted imaging in axial, coronal and sagittal planes, T1-weighted, FLAIR, and DWI images in the axial plane. Patients who showed any apparent lesion on MRI were excluded from the study. T2-weighted images in three orthogonal planes were used to localize the voxel in left frontal lobe white matter (FWM) and left basal ganglia (BG) for single voxel MRS. Single voxel MRS spectra were acquired with a point resolved spectroscopy (PRESS) localization pulse sequence at an echo time (TE) of 35 ms and a repetition time (TR) of 2000 ms with 64 or 128 scans. Automated preprocessing and determination of absolute concentrations of metabolites were estimated using LCModel by water scaling method and the Cramer-Rao lower bounds for all metabolites analyzed in the study were below 15\%. Levels of total N-acetyl aspartate (tNAA), total choline (tCho), glutamate + glutamine (Glx), total creatine (tCr), were measured. Cognition was tested using a battery of tests validated for Indian population. The cognitive domains tested were the memory, attention-information processing, abstraction-executive, simple and complex perceptual motor skills. Z-scores normalized according to age, sex and education standard were used to calculate dysfunction in these individual domains. The NCD was defined as dysfunction with Z-score ≤ 2 in at least two domains. One-way ANOVA was used to compare the difference in brain metabolites between the patients and healthy subjects. Results: NCD was found in 23 (53%) patients. There was no significant difference in age, CD4 count and viral load between the two groups. Maximum impairment was found in the domains of memory and simple motor skills i.e., 19/43 (44%). The prevalence of deficit in attention-information processing, complex perceptual motor skills and abstraction-executive function was 37%, 35%, 33% respectively. Subjects with NCD had a higher level of Glutamate in the Frontal region (8.03 ± 2.30 v/s. 10.26 ± 5.24, p-value 0.001). Conclusion: Among newly diagnosed, ART-naïve retroviral disease patients from India, cognitive decline was found in 53\% patients using tests validated for this population. Those with neurocognitive decline had a significantly higher level of Glutamate in the left frontal region. There was no significant difference in age, CD4 count and viral load at initiation of ART between the two groups.

Keywords: HIV, neurocognitive decline, neurometabolites, magnetic resonance spectroscopy

Procedia PDF Downloads 157

Authors: Ahuja Ashish, Nain Prabhdeep Singh

Abstract:

Introduction: Polycystic ovarian syndrome(PCOS) is the most common endocrine disorder among women of reproductive age.Pcos encompasses a broad spectrum of signs&symptoms of ovary dysfunction,obesity,blood pressure,insulin resistance & infertility. Bariatric Surgery can be an effective means of weight loss in Pcos & curing infertility. Materials and Methods: 15 female patients were enrolled in the study from 2012-2014.66%(n=10) were in age group of 20-25 years,33%(n=5) were in age group of 25-33 years who underwent. Bariatric surgery in form of Laproscopic sleeve Gastrectomy(LSG)& Roux-en-Y gastric bypass. LSG 73%(n=11), RYGB26% (n=4). Results: There was a significant improvement in obesity (60% excess weight loss)over 1 year after bariatric surgery, in 12 patients there was gross improvement in restoration of menstrual cycle who had irregular menstrual cycle. In 80% patients the serum insulin level showed normal value. Over two years 8 patients become pregnant. Conclusions: 1)Obese women with Pcos maybe able to conceive after Bariatric Surgery. 2) Women with Pcos should only consider bariatric surgery if they were already considering it for other reasons to treat obesity, blood pressure & other co-morbid conditions.

Keywords: obesity, bariatric surgery, polycystic ovarian syndrome, infertility

Procedia PDF Downloads 270

Authors: S. Thangapandiyan, S. Miltonprabu

Abstract:

Fl (Fl) exposure engenders neurodegeneration and induces oxidative stress in the brain. The Neuroprotective role of EGCG on oxidative stress-mediated neurotoxicity in Fl intoxicated rat hippocampus has not yet been explored so far. Hence, the present study is focused on witnessing whether EGCG (40mg/kg) supplementation prevents Fl induced oxidative stress in the brain of rats with special emphasis on the hippocampus. Fl (25mg/kg) intoxication for four weeks in rats showed an increase in Fl concentration along with the decrease the AChE, NP, DA, and 5-HT activity in the brain. The oxidative stress markers (ROS, TBARS, NO, and PC) were significantly increased with decreased enzymatic (SOD, CAT, GPx, GR, GST, and G6PD) and non-enzymatic antioxidants (GSH, TSH, and Vit.C) in Fl intoxicated rat hippocampus. Moreover, Fl intoxicated rats exhibited an intrinsic and extrinsic pathway mediated apoptosis in the hippocampus of rats. Fl intoxication significantly increased the DNA damage as evidenced by increased DNA fragmentation. Furthermore, the toxic impact of Fl on hippocampus was also proved by the immunohistochemical, histological, and ultrastructural studies. Pre-administration of EGCG has significantly protected the Fl induced oxidative stress, biochemical changes, cellular apoptotic, and histological alternations in the hippocampus of rats. In conclusion, EGCG supplementation significantly attenuated the Fl induced oxidative stress mediated neurotoxicity via its free radical scavenging and antioxidant activity.

Keywords: brain, hippocampal, NaF, ROS, EGCG

Procedia PDF Downloads 361

Authors: Ryan M. Monti, Bijal Mehta

Abstract:

In cases of massive pulmonary embolism, defined as acute pulmonary embolism presenting with systemic hypotension or right ventricular dysfunction and impending failure, there is indication that unconventional therapies, such as phosphodiesterase inhibitors, endothelin receptor antagonists, and/or prostacyclin analogs may decrease the morbidity and mortality. Based on the premise that dilating the pulmonary artery will decrease the pulmonary vascular pressure, while simultaneously decreasing the aggregation of platelets, it can be hypothesized that increased blood flow through the pulmonary artery will decrease right heart strain and subsequent morbidity and mortality. While this theory has yet to be formally studied, the recommendations for treating massive pulmonary embolism with phosphodiesterase inhibitors, endothelin receptor antagonists, and/or prostacyclin analogs in conjunction with the current standards of care in massive pulmonary embolism should be formally studied. In particular, patients with massive PE who are unable to undergo thrombolysis/surgical intervention may be the ideal population to study the use of these treatments to determine any decrease in mortality and morbidity (short term and long term).

Keywords: acute pulmonary thromboembolism, treatment of pulmonary embolism, use of phosphodiesterase inhibitors, endothelin receptor antagonists, prostacyclin analogs in PE

Procedia PDF Downloads 197

Authors: A. B. Amna, M. A. E. Samia, A. K. Hassan

Abstract:

The clinical, pathological, hematological and biological changes in Newzealand rabbits groups given daily oral doses of 0.1,0.25 and 0.5 ml/kg body weight/day of Cpmbopogon proximus oil extract were investigated in an experiment durated for 21 days. Other than the dose co-related mortality rates, the clinical signs were observed daily after dosing to be low appetite and nervous signs including restlessness and increased consciousness. Pulmonary excretion of the oil extract led to bloody spots on the lungs, lymphocyte infiltration, congestion and edema. Renal glumeruli manifested lymphocyte infiltration in addition to shrinkages and easinophilic material in the medulla, if considered with the corticomedullary generalized necrosis and the significant changes in urea, they can explain the renal dysfunction. Hepatic malfunction was manifested by significant changes in serum alkaline phosphatase and aspartate transferases accompanied by the congested, fatty changed livers. The direct physical effect of the extracted oil was detected by the catarrhal inflammation of the intestines.There was no significant haematological change except for the slight changes in RBCs and MCVs in rabbits given the highest dose. Future work for Cpmbopogon proximus oil extract was forwarded and practical implications of the result were highlighted.

Keywords: toxicity, cymbopogon proximus (maharaib), oil extract, Newzealand rabbits

Procedia PDF Downloads 451

Authors: Stephanie Elizabeth Talder

Abstract:

Art therapy is a field that is growing exponentially with new groundbreaking discoveries that allow for embodying trauma and mental healing. Applied theatre and performance is a continuously growing and developing field that can help people who are struggling to work through traumatic experiences plaguing their life. By using performance, there is an ability to target sensitive topics in a manner that does not lead to re-traumatization. The use of theatre as a healing agent has been going on for centuries, with clear applications beginning in Greek theatre and tragedy. When working with complex mental illness, issues such as PTSD, anxiety, and depression can be managed and worked through. A central component of drama therapy is the connection to community and self. The ability to connect mind-body to stories as well as to other people allows for healing to occur. There is the opportunity for healing through emotional catharsis and community building. Applied theatre in connection to the medical field can allow for there to be a meaningful impact made on mental health. Though there is still a significant amount of progress to be made within the stigmatization of mental health problems, bringing in a varying option that allows for there to be movement and community building possesses a strong ability to impact people in a positive way.

Keywords: applied theatre, drama therapy, art therapy, performance, theatre

Procedia PDF Downloads 51

Authors: Leila Karshenas, Hamid Reza Khodaei, Behnaz Mahdavi

Abstract:

We know that nitric oxide (NO) plays an important role in all sexual activities of animals. It is made in body from NO synthase enzyme and L-arginin molecule. NO can bound with sulfur-iron complexes and because production of steroid sexual hormones is related to enzymes which have this complex, NO can change the activity of these enzymes. NO affects many cells including endothelial cells of veins, macrophages and mast cells. These cells are found in testis leydig cells and therefore are important source of NO in testis tissue. Minimizing damages to sperm at the time of sperm freezing and thawing is really important. The goal of this study was to determine the function of NO before freezing and its effects on quality and viability of sperms after thawing and incubation. 4 Holstein bulls were selected from the age of 4, and artificial insemination was done for 3 weeks (2 times a week). Treatments were 0, 10, 50 and 100 nm of sodium nitroprusside (SNP). Data analysis was performed by SAS98 program. Also, mean comparison was done using Duncan's multiple ranges test (P<0.05). Concentrations used was found to increase motility and viability of spermatozoa at 1, 2 and 3 hours after thawing significantly (P<0.05), but there was no significant difference at zero time. SNP levels reduced the amount of lipid peroxidation in sperm membrane, increased acrosome health and improved sample membranes especially in 50 and 100 nm treatments. According to results, adding SNP to semen diluents increases motility and viability of spermatozoa. Also, it reduces lipid peroxidation in sperm membrane and improves sperm function.

Keywords: sperm motility, nitric oxide, lipid peroxidation, spermatozoa

Procedia PDF Downloads 330

Authors: Rostika Flora, Muhammad Zulkarnain, Syokumawena

Abstract:

Background: Aerobic physical exercises are recommended to keep body fit and healthy although physical exercises themselves can increase body metabolism and oxygen and can lead into tissue hypoxia. Oxygen pressure can serve as Vascular Endhothelial Growth Factor (VEGF) regulator. Hypoxia increases gene expression of VEGF through ascendant regulation of HIF-1. VEGF is involved in regulating angiogenesis process. Aerobic physical exercises can increase the concentration of VEGF in brain and enables angiogenesis process. We have investigated the influence of aerobic physical exercise to the VGEF concentration of wistar rat’s brain. Methods: This was experimental study using post test only control group design. Independent t-test was used as statistical test. The samples were twenty four wistar rat (Rattus Norvegicus) which were divided into four groups: group P1 (control group), group P2 (treatment group with once-a-week exercise), group P3 (treatment group with three time-a-week exercise), and group P4 (treatment group with seven time-a-week exercise). Group P2, P3, and P4 were treated with treadmil with speed of 20 m/minute for 30 minutes. The concentration of VEGF was determined by ELISA. Results: There was a significant increase of VEGF in treatment group compared with control one (<0.05). The maximum increase was found in group P2 (129.02±64.49) and the minimum increase was in group P4 (96.98±11.20). Conclusion: The frequency of aerobic physical exercises influenced the concentration of Vascular Endhothelial Growth Factor (VEGF) of brain tissue of Rattus Norvegicus.

Keywords: brain tissue, hypoxia, physical exercises, vascular endhothelial growth factor

Procedia PDF Downloads 456

Authors: Kambiz Hassanzadeh, Seyedeh Shohreh Ebrahimi, Shahrbanoo Oryan, Arman Rahimmi, Esmael Izadpanah

Abstract:

Parkinson’s disease is one of the most prevalent neurodegenerative diseases which occurs in elderly. There are convincing evidences that oxidative stress has an important role in both the initiation and progression of Parkinson’s disease. Thymoquinone (TQ) is shown to have antioxidant and anti-inflammatory properties in invitro and invivo studies. It is well documented that TQ acts as a free radical scavenger and prevents the cell damage. Therefore this study aimed to evaluate the effect of TQ on motor and non-motor symptoms in animal model of Parkinson’s disease. Male Wistar rats (10-12 months) received rotenone (1mg/kg/day, sc) to induce Parkinson’s disease model. Pretreatment with TQ (7.5 and 15 mg/kg/day, po) was administered one hour before the rotenone injection. Three motor tests (rotarod, rearing and bar tests) and two non-motor tests (forced swimming and elevated plus maze) were performed for behavioral assessment. Our results indicated that TQ significantly ameliorated the rotenone-induced motor dysfunction in rotarod and rearing tests also it could prevent the non-motor dysfunctions in forced swimming and elevated plus maze tests. In conclusion we found that TQ delayed the Parkinson's disease induction by rotenone and this effect might be related to its proved antioxidant effect.

Keywords: Parkinson's disease, thymoquinone, motor and non-motor symptoms, neurodegenerative disease

Procedia PDF Downloads 517