Anthony Kashou

Evaluation of Sperm Proteins in Infertile Men: A Proteomic Approach

In this study, the sperm protein profile was compared between fertile and infertile men using 2-dimensional gel electrophoresis, liquid chromatography mass spectrometer analysis, and matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry. Four unique proteins, semenogelin II precursor, prolactin-induced protein, clusterin isoform 1, and prostate-specific antigen isoform 1 preproprotein, were predominantly present in the semen of healthy men; however, semenogelin II precursor and clusterin isoform 1 were not seen in the semen of infertile men, suggesting unique differences in the spermatozoa protein profiles of fertile and infertile men.

Proteomics: a subcellular look at spermatozoa

BackgroundMale-factor infertility presents a vexing problem for many reproductively active couples. Many studies have focused on abnormal sperm parameters. Recent advances in proteomic techniques, especially in mass spectrometry, have aided in the study of sperm and more specifically, sperm proteins. The aim of this study was to review the current literature on the various proteomic techniques, and their usefulness in diagnosing sperm dysfunction and potential applications in the clinical setting.MethodsReview of PubMed database. Key words: spermatozoa, proteomics, protein, proteome, 2D-PAGE, mass spectrometry.ResultsRecently employed proteomic methods, such as two-dimensional polyacrylamide gel electrophoresis, mass spectrometry, and differential in gel electrophoresis, have identified numerous sperm-specific proteins. They also have provided a further understanding of protein function involved in sperm processes and for the differentiation between normal and abnormal states. In addition, studies on the sperm proteome have demonstrated the importance of post-translational modifications, and their ability to bring about physiological changes in sperm function. No longer do researchers believe that in order for them to elucidate the biochemical functions of genes, mere knowledge of the human genome sequence is sufficient. Moreover, a greater understanding of the physiological function of every protein in the tissue-specific proteome is essential in order to unravel the biological display of the human genome.ConclusionRecent advances in proteomic techniques have provided insight into sperm function and dysfunction. Several multidimensional separation techniques can be utilized to identify and characterize spermatozoa. Future developments in bioinformatics can further assist researchers in understanding the vast amount of data collected in proteomic studies. Moreover, such advances in proteomics may help to decipher metabolites which can act as biomarkers in the detection of sperm impairments and to potentially develop treatment for infertile couples.Further comprehensive studies on sperm-specific proteome, mechanisms of protein function and its proteolytic regulation, biomarkers and functional pathways, such as oxidative-stress induced mechanisms, will provide better insight into physiological functions of the spermatozoa. Large-scale proteomic studies using purified protein assays will eventually lead to the development of novel biomarkers that may allow for detection of disease states, genetic abnormalities, and risk factors for male infertility. Ultimately, these biomarkers will allow for a better diagnosis of sperm dysfunction and aid in drug development.

Assessment of Oxidative Stress in Sperm and Semen

The chemiluminescence method is the most commonly employed technique as a direct measurement of reactive oxygen species (ROS) generation by spermatozoa. This assay is capable of quantifying both intracellular and extracellular ROS. Moreover, the use of various probes allows for differentiation between superoxide and hydrogen peroxide production by spermatozoa. When the total antioxidant reserves are overwhelmed by excessive production of ROS, it results in oxidative stress. Therefore correct measurement of both ROS and total antioxidant capacity (TAC) is essential in the assessment of oxidative stress in sperm and semen. This chapter describes the methodological approach for measuring seminal oxidative stress through the use of chemiluminescence assay for accurate measurement of ROS and the colorimetric assay for measurement of TAC.

Oxidants and Antioxidants in the Pathogenesis of HIV/AIDS

Human immunodeficiency virus (HIV) has predominantly been considered the main cause in the progression of acquired immunodeficiency syndrome (AIDS). However, many researchers believe that there are co-factors involved along the way that may play a critical role in its development. Elevated levels of reactive oxygen species (ROS) have been established to be present at the onset of infection. Additionally, the delayed response by the immune system upon infection may be due to an initial depletion of antioxidants, which play a critical role in scavenging excess ROS to maintain normal physiological conditions. This pro-oxidant/antioxidant imbalance results in a condition known as oxidative stress (OS). OS has been reported to be an integral element in the progression of many diseases, including AIDS. Therefore, it is presumed that antioxidant treatment may provide a promising and cost-effective therapeutic approach in treating HIV-infected individuals on a global scale. Although HIV infection presents one of the most arduous complications to humans worldwide, awareness of its origin, adverse effects, and potential treatment remain confined to a limited population. The aim of this article is to inform the reader of how AIDS developed into a global epidemic so rapidly, while emphasizing the relationship between oxidants and antioxidants in the pathogenesis of HIV/AIDS. A basic review of reduction/oxidation (redox) reactions is provided to understand how such simple introductory concepts can have such profound effects on the body. This serves as an essential building block to the topics that follow: ROS, antioxidants, and OS in HIV disease. Moreover, it allows for us to better define and elucidate OS as an often-overlooked link between HIV-infection and the progression of AIDS, as well as potential antioxidant treatment.

Environmental Toxicants and Testicular Apoptosis

When apoptosis is improperly activated or regulated in the testis, infertility or even cancer can result. Studies have implicated elevated rates of apoptosis in infertile male patients. Pinpointing how environmental toxicity affects apoptosis is important for the advancement of preventative medicine and behavior, especially as potentially harmful compounds continue to proliferate in households and workplaces. Moreover, familiarity with testicular processes, particularly the induction of apoptosis, is essential for promoting male fertility. This review examines environmental toxicants that have been implicated in testicular apoptosis. We elucidate the mechanistic pathways through which specific xenobiotic compounds trigger cell death in the testis. This review highlights the role of oxidative stress in mediating these apoptotic actions.

Is There a Link between Exercise and Male Factor Infertility

The beneficial effects of physical exercise on general health are well known; however, as exercise imposes great physical stress that challenges homeostasis, it can be detrimental to certain organs/systems of the body when it is exhaustively performed. Decreased seminal parameters and sex hormone levels have been reported in male athletes and, therefore, a possible impairment of male fertility has been linked to exercise in a volume, intensity, and modality dependent-manner. Also, inherent characteristics of sportsmen (e.g. training level, adaptive capacity) may modify the response. This article aims to review the relevant literature regarding exercise and male factor infertility, while at the same time explores the possible underlying mechanisms that might be involved in this observable fact.

Oxidative Stress and the Use of Antioxidants for Idiopathic OATs

Aim: To examine the effects of ROS and OS on male fertility and to evaluate the use of antioxidants as a means of treatment to improve fertilization rates in subfertile males suffering from idiopathic oligoasthenoteratozoospermia (iOAT). Methods: Review of PubMed database. Results: Current research notes ROS-associated male factor infertility to be the most common potential etiology of impaired sperm quality. The various effects of these oxidants may be neutralized by antioxidants. Although antioxidant therapy has shown to potentially treat iOAT by improving semen parameters, its success remains limited. Our review calls for a deeper look and understanding of the type(s), dosage, and duration of antioxidant treatment used in order to apply its use in a clinical setting.

A Case of Recurrent Takotsubo Cardiomyopathy: Not a Benign Entity

Takotsubo cardiomyopathy is a relatively uncommon condition triggered by severe physical and/or emotional stress. It is characterized by transient ventricular wall dysfunction in the absence of coronary artery disease (CAD). Herein, we report a case of a 59-year-old female who had three episodes of recurrent Takotsubo cardiomyopathy. On each occasion, she presented with symptoms of acute coronary syndrome accompanied by left ventricular wall motion abnormalities; however, repeat cardiac catheterization failed to show CAD. Each recurrence resulted in resolution of her symptoms and recovery of left ventricular function. While emotional triggers were identified, on two occasions, the patient presented with ventricular fibrillation for which an implantable cardioverter defibrillator (ICD) was ultimately placed. We encourage clinicians to no longer look at Takotsubo cardiomyopathy as a benign, reversible disease process, but rather as a pathological entity with real, life-threatening complications that may be managed with ICD placement. J Med Cases. 2018;9(3):98-102 doi: https://doi.org/10.14740/jmc3011w

A Rare Case of Left Main Coronary Artery Atresia

Left main coronary artery (LMCA) atresia remains one of the most rare congenital coronary anomalies. On average, there is less than one reported case each year. Because patients with LMCA atresia that make it to adulthood tend to remain asymptomatic and often are unaware of their condition, the diagnosis is often made incidentally. We report a case of LMCA atresia in a 76-year-old male with a history of seizure disorder and medication non-compliance who presented to the hospital with acute coronary syndrome in the setting of status epilepticus. Workup revealed ST elevation and minimally elevated troponin levels. Hours later, troponin levels continued to trend up, but the ST elevation resolved. Catheterization and coronary angiography revealed a dominant right coronary artery and absent LMCA. Aortography confirmed the diagnosis of LMCA atresia. J Med Cases. 2017;8(12):381-382 doi: https://doi.org/10.14740/jmc2946w

Insights into an Award-Winning Summer Internship Program: The First Six Years.

Since its inception in 2008, the American Center for Reproductive Medicines summer internship program in reproductive research and writing has trained 114 students from 23 states within the United States and 10 countries worldwide. Its fundamental goal is to inspire pre-medical and medical students to embrace a career as a physician-scientist. During this intensive course, established scientists and clinicians train interns in the essential principles and fundamental concepts of bench research and scientific writing. Over the first six years (2008~2013), interns have collectively published 98 research articles and performed 12 bench research projects on current and emerging topics in reproductive medicine. Interns have also developed and honed valuable soft skills including time management, communication and presentation skills, as well as life values, which all enhance personal and professional satisfaction. Program graduates are able to recognize the value of medical research and its potential to impact patient care and gain insight into their own career pathway. Between 2011 and 2014, the internship program was thrice awarded a Scholarship in Teaching Award by Case Western Reserve School of Medicine for its innovative teaching approach and positive impact on medical education and student careers. This report highlights the demographics, logistics, implementation, feedback, and results of the first six years of the American Center for Reproductive Medicines summer internship program at Cleveland Clinic (Cleveland, OH, USA). This may be helpful to other research and academic institutions considering implementing a similar program. In addition, it creates awareness among potential physician-scientists of what the world of research has to offer in both scientific writing and bench research. Finally, it may stimulate further discussion regarding narrowing the gap between physicians and scientists and refinement of the current program.