Chemicals and Drugs Commons^™

Effect Of Chronic Angiotensin Ii Infusion On Plasma Tnfalpha And Il 6 Levels In Adiponectin Deficient Mice, Alexis O'Brien, Minnette Smith, Jaya Pamidimukkala

College of Osteopathic Medicine (TUN) Publications and Research

Chronic low grade inflammation plays an integral part in the development of many types of cardiovascular diseases. Adipose tissue is a well known source of many proinflammatory mediators. Adiponectin (APN) is one of the few proteins secreted by the adipose tissue that is known to have anti-inflammatory properties. Our research goal is to understand if APN deficiency contributes to a proinflammatory milieu especially when provided with an appropriate stimulus. Angiotensin II (ANGII) is a well known prohypertensive agent. Recently, ANGII has emerged as a growth factor and stimulator of proinflammatory cytokine expression in cardiovascular & renal tissue. The present study …

The Hormones Of The Placenta, Shaya Oratz

The Science Journal of the Lander College of Arts and Sciences

The human pregnancy begins with fertilization and implantation. As the embryo evolves and develops within the uterus of the mother, the placenta is formed. The placenta is a transient organ that develops to meet and accommodate specific needs during pregnancy. Its two major functions are the exchange of nutrients and gases between the mother and fetus and its role as an endocrine unit. Through the production and release of many hormones the placenta works to regulate the many necessary physiological changes in the mother in order to maintain the pregnancy, meet the needs of the developing fetus and prepare the …

The Effect Of Maté On Enzymes Involved In The Recovery From Oxidative Stress, Amina Sadik, Theodore Chang

College of Osteopathic Medicine (TUN) Publications and Research

In comparing the effect of Maté to that of green tea, it has been shown that Maté has higher anti-oxidative properties. We have shown that the extract of Yerba Maté, paraguariensis, leaves does indeed have strong anti-oxidative properties through the evaluation of its scavenging activity and its ability of assist cardiomyocytes in their recovery from induced oxidative stress using both spectroscopy, a colorimetric assay and flow cytometry. In order to elucidate the mechanism behind this action, we quantified the enzymes known to be expressed naturally by cells under oxidative stress such as glutathione peroxidase, superoxide dismutase, and catalase. These enzymes …

Perspectives On: Cyclic Nucleotide Microdomains And Signaling Specificity, Jeffrey W. Karpen

Touro College of Osteopathic Medicine (Middletown) Publications and Research

The author provides an introduction to a special issue on cyclic nucleotides concerning four areas in cAMP compartmentation.

Cardiolipin Prevents Membrane Translocation And Permeabilization By Daptomycin, Tianhua Zhang, Jawad K. Muraih, Nasim Tishbi, Jennifer Herskowitz, Rachel L. Victor, Jared Silverman, Stephanie Uwumarenogie, Scott D. Taylor, Michael Palmer, Evan Mintzer

Lander College of Arts and Sciences Publications and Research

Daptomycin is an acidic lipopeptide antibiotic that, in the presence of calcium, forms oligomeric pores on membranes containing phosphatidylglycerol. It is clinically used against various Gram-positive bacteria such as Staphylococcus aureus and Enterococcusspecies. Genetic studies have indicated that an increased content of cardiolipin in the bacterial membrane may contribute to bacterial resistance against the drug. Here, we used a liposome model to demonstrate that cardiolipin directly inhibits membrane permeabilization by daptomycin. When cardiolipin is added at molar fractions of 10 or 20% to membranes containing phosphatidylglycerol, daptomycin no longer forms pores or translocates to the inner membrane leaflet. Under …

Differential Actions Of Orexin Receptors In Brainstem Cholinergic And Monoaminergic Neurons Revealed By Receptor Knockouts: Implications For Orexinergic Signaling In Arousal And Narcolepsy, Kristi Kohlmeier, Christopher Tyler, Mike Kalogiannis, Masaru Ishibashi, Iryna Gumenchuk, Masashi Yanagisawa, Christopher S. Leonard

NYMC Faculty Publications

Orexin neuropeptides influence multiple homeostatic functions and play an essential role in the expression of normal sleep-wake behavior. While their two known receptors (OX1 and OX2) are targets for novel pharmacotherapeutics, the actions mediated by each receptor remain largely unexplored. Using brain slices from mice constitutively lacking either receptor, we used whole-cell and Ca(2+) imaging methods to delineate the cellular actions of each receptor within cholinergic [laterodorsal tegmental nucleus (LDT)] and monoaminergic [dorsal raphe (DR) and locus coeruleus (LC)] brainstem nuclei-where orexins promote arousal and suppress REM sleep. In slices from OX(-/-) 2 mice, orexin-A (300 nM) elicited wild-type responses …

Can Marijuana Be Harmful When Used Prenatally Or During Adolescence?, Penninah Dean

The Science Journal of the Lander College of Arts and Sciences

Marijuana is a popular recreational drug with a strong following campaigning to legalize it for both medicinal and recreational use. This paper serves to illustrate the harmful effects of marijuana use as it pertains to prenatal, adolescent and adult use. By understanding the methods of absorption and mechanism of interaction in the body, we can see a correlation between the effects of marijuana and its toxicity. Through extensive research of case studies on marijuana use we were able to determine marijuana’s harmful effects physically, developmentally and cognitively. Through these methods of research, it can be concluded that marijuana has detrimental …

The Carcinogenic Effects Of Aspartame, Devora Sara Gelbfish

The Science Journal of the Lander College of Arts and Sciences

Aspartame, one of the most common artificial sweeteners, is used as a food additive worldwide. Because of early experimentation with rats linking aspartame to higher risk of cancer, there is much concern regarding the safety of aspartame. However, analytical review and numerous subsequent studies have disproven previous experimentation and reaffirmed that aspartame consumption in humans does not increase the risk of cancers. At the current time there is no credible evidence to support the idea that aspartame is carcinogenic. The evidence confirms that at current levels of consumption aspartame is a safe alternative to sucrose.

Cytoplasmic Actin: Structure And Function, Justin Konig

The Science Journal of the Lander College of Arts and Sciences

Cytoplasmic actin plays a crucial role in cellular structure, cell motility, intracellular transportation, and the cell cycle. Two isoforms of cytoplasmic actin have been identified, β and γ. Although their amino acid sequence is nearly identical, these two isoforms are encoded by different genes located on different chromosomes. Recent research has found that, despite their similarities, the two isoforms of cytoplasmic actin have distinct functions. This paper will review the structural and functional differences between the two isoforms, concluding with a discussion of some mutations that have been linked to disease.

Do Photoperiodic Changes In Melatonin Secretion Detrimentally Affect The Female Reproductive Cycle?, Riki Szlafrok

The Science Journal of the Lander College of Arts and Sciences

Melatonin, better known as "the hormone of darkness," is secreted by the pineal gland during the night and helps us fall asleep. Because its internal regulation depends on light, melatonin is part of chronobiology, the study of biological mechanisms and their adaptations to lunar and solar related rhythms (Klein et al. 1991). Therefore, photoperiod changes greatly impact melatonin concentration, influencing changes in neuronal and hormonal mechanisms of the photo neuro-endocrine systems, namely reproduction. Research has shown that a disruption in the circadian rhythm of melatonin due to photoperiod changes detrimentally affects the rhythmic function of the female reproductive cycle. Research …

Melatonin And Its Effect On Learning And Memory, Nechama Leah Bauman (Cahn)

The Science Journal of the Lander College of Arts and Sciences

Melatonin is a neurohormone produced by the pineal gland and secreted into the body in a circadian rhythm. Melatonin is known to be involved in many vital body functions, including sleep, reproduction, and immune response. Exogenous melatonin, sold as over the counter natural supplements in drugstores, is commonly taken by many people to help cure various ailments. Melatonin also plays a role in the hippocampus. This paper investigates the effects of melatonin on long-term potentiation in the hippocampus. Long-term potentiation, described as a long-lasting strengthening of synapses between nerve cells, is thought to be responsible for long-term memory retention. It …

How Biological And Non-Biological Disease Modifying Drugs Are Used In The Treatment Of Rheumatoid Arthritis, Esther Mantel

The Science Journal of the Lander College of Arts and Sciences

The following is an excerpt from the introduction to this article: Rheumatoid arthritis is a long-term disease that leads to chronic inflammation of the joints and the surrounding tissue. Effects of the inflammation are pain and destruction of the bone and cartilage, which leads to severe disability and, possibly, shorter life expectancy. That is why early diagnosis and aggressive treatment is a fundamental strategy to stop the progression of the disease and suppress the inflammation before the damage is irreversible.

Tlr4 Mutation Reduces Microglial Activation, Increases Aβ Deposits And Exacerbates Cognitive Deficits In A Mouse Model Of Alzheimer's Disease, Min Song, Jingji Jin, Jinghong Kou, Abhinandan Pattanayak, Jamaal Rehman, Hong-Duck Kim, Ken-Ichiro Fukuchi

NYMC Faculty Publications

BACKGROUND: Amyloid plaques, a pathological hallmark of Alzheimer's disease (AD), are accompanied by activated microglia. The role of activated microglia in the pathogenesis of AD remains controversial: either clearing Aβ deposits by phagocytosis or releasing proinflammatory cytokines and cytotoxic substances. Microglia can be activated via toll-like receptors (TLRs), a class of pattern-recognition receptors in the innate immune system. We previously demonstrated that an AD mouse model homozygous for a loss-of-function mutation of TLR4 had increases in Aβ deposits and buffer-soluble Aβ in the brain as compared with a TLR4 wild-type AD mouse model at 14-16 months of age. However, it …

What Is New For An Old Molecule? Systematic Review And Recommendations On The Use Of Resveratrol, Ole Vang, Nihal Ahmad, Karen Brown, Anna Csiszar, Thomas Szekeres, Thomas Walle, Joseph M. Wu

NYMC Faculty Publications

BACKGROUND: Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark.

METHODOLOGY: Literature search in databases as PUBMED and ISI Web of Science in combination with manual search was used to answer the following five questions: (1)Can resveratrol be recommended in the prevention or treatment of …

A Survey Of Oxidative Paracatalytic Reactions Catalyzed By Enzymes That Generate Carbanionic Intermediates: Implications For Ros Production, Cancer Etiology, And Neurodegenerative Diseases, Victoria Bunik, John Schloss, John T. Pinto, Natalia Dudareva, Arthur J L Cooper

NYMC Faculty Publications

Enzymes that generate carbanionic intermediates often catalyze paracatalytic reactions with O2 and other electrophiles not considered “normal” reactants. For example, pyridoxal 5′-phosphate (PLP)—containing pig kidney dopa decarboxylase oxidizes dopamine with molecular O2 to 3,4-dihydroxyphenylacetaldehyde at about 1% of the rate at which it catalyzes nonoxidative dopa decarboxylation. The mutant Y332F enzyme, however, catalyzes stoichiometric conversion of dopa to 3,4-dihydroxyphenylacetaldehyde, suggesting that even minor structural changes may alter or initiate paracatalytic reactions catalyzed by certain enzymes. Carbanions generated by several thiamine diphosphate (ThDP)—dependent enzymes react with different electrophiles, transforming some xenobiotics and endogenous compounds into potentially biologically hazardous products. The detrimental …

The Role Of Ghrelin And Leptin In Obesity: Is Exogenous Administration Of These Hormones A Possible Drug Therapy?, Peri Eckstein

The Science Journal of the Lander College of Arts and Sciences

Ghrelin and leptin are two hormones that have been recognized to have a major influence on energy balance. Leptin is a mediator of long term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin, on the other hand, is a fast acting hormone, playing a role in meal initiation. As a growing number of people suffer from obesity, understanding the mechanisms by which various hormones and neurotransmitters influence energy balance has been a subject of intense research. This paper provides background on leptin and ghrelin hormones, their role in food intake and body weight in humans, …

Health Risks Of Very Low Cholesterol, Menachem Nagar

The Science Journal of the Lander College of Arts and Sciences

Cholesterol is a molecule central to all human physiological processes at systemic as well as cellular levels. Cholesterol, combined with Apolipoprotein B as low-density lipoprotein (LDL) has been the focus of scientific research because the molecule has been proven to play a role in the development of cardiovascular disease, a disease of pandemic proportions. Considerable scientific and medical attention has been devoted to identifying the role and management of high levels of total serum cholesterol in order to address this global health burden, creating large scale awareness regarding lowering cholesterol concentration in circulation. However, the same molecule, combined into various …

The Effect Of Melatonin On The Ovaries, Jaclyn Starr

The Science Journal of the Lander College of Arts and Sciences

Melatonin is a very small molecule whose effects can be both detrimental and beneficial to the ovaries depending on its concentration. Too much of anything is usually not good and so is the case with melatonin. Very high doses can be damaging, but in the right amount melatonin may be able to combat various diseases and increase the chances for fertility in women.

Mechanisms Of Oxidant Generation By Catalase, Diane E. Heck, Michael Shakarjian, Hong-Duck Kim, Jeffrey Laskin, Anna M. Vetrano

NYMC Faculty Publications

The enzyme catalase converts solar radiation into reactive oxidant species (ROS). In this study, we report that several bacterial catalases (hydroperoxidases, HP), including Escherichia coli HP-I and HP-II also generate reactive oxidants in response to ultraviolet B light (UVB). HP-I and HP-II are identical except for the presence of NADPH. We found that only one of the catalases, HPI, produces oxidants in response to UVB light, indicating a potential role for the nucleotide in ROS production. This prompts us to speculate that NADPH may act as a cofactor regulating ROS generation by mammalian catalases. Structural analysis of the NADPH domains …

Aspartame: A Sweet Toxin?, Atara Rena Degani

The Science Journal of the Lander College of Arts and Sciences

L-aspartyl-L-phenylalanyl-methyl ester, commonly known as aspartame, is one of the most widely used and controversial sweeteners. Many have questioned the safety of this chemical, concerned that it may be neurotoxic and carcinogenic. Numerous studies have been conducted on the three basic constituents of aspartame: aspartic acid, phenylalanine and methanol; scientists have tried to determine whether the ingestion of aspartame will cause a significant increase in blood plasma levels of these chemicals, and whether such an increase is dangerous. This review analyzes various studies conducted on the health effects of these metabolitic byproducts of aspartame.

Atherosclerosis And Antioxidants, Yehoshua Lewis

The Science Journal of the Lander College of Arts and Sciences

Cellular lipid oxidation is a known cause for the cascade leading to the formation of lipid laden foam cells, which can cause of atherosclerosis. While statins and antioxidants have recently come under question in the amelioration of atherosclerosis, Flavonoids have recently been touted as a powerful antioxidant and suppresser of atherosclerosis. This paper will attempt to show why statins and vitamin E have come under scrutiny, and how the desired effects of Flavonoids can be attributed to the role it plays in increased paraoxonase-1 activity (a known anti inflammatory associated with HDL), decreased C- Reactive protein activity, and increased nitric …

Pompe’S Disease And The Effects Of Alpha-Glucosidase Deficiency, Aaron Richler

The Science Journal of the Lander College of Arts and Sciences

The following is an excerpt from the introduction of this article: The energy that the body needs in order to function is obtained from carbohydrates that we get through our diet. These carbohydrates are monosacharides, disaccharides and polysacharides. The polysaccharides and disaccharides are hydrolyzed to monosaccharide’s such glucose (which comprises roughly 80%) fructose and galactose. Most cells convert the fructose and galactose to glucose. The body can use the glucose or store it. If energy is needed, glucose can be oxidized through the many reactions of glycolysis which gives a net production of 2 ATP and 2 NADH from one …

Vitamin D3, Aryeh Grossman

The Science Journal of the Lander College of Arts and Sciences

The following is the introduction of this article: Vitamin D is the only vitamin that is free. It can be easily obtained from exposure to sunlight and yet more than 60% of Americans are Vitamin D deficient (Ginde et al., 2009; Bones, Vitamin D, and Calcium, n.d). The significance of Vitamin D can’t be emphasized enough and is often overlooked. Some its profound effects are apparent in the prevention of various diseases such as cancer, multiple sclerosis, and cardiovascular disease et cetera. Many lives can be spared each year just by taking Vitamin D. From cancer alone, 23,000 deaths can …

Folic Acid And Neural Tube Defects, Rachel Leah Feinstein

The Science Journal of the Lander College of Arts and Sciences

The following is an excerpt of this article: Neural tube defects (NTD) are the most common types of birth defects. Research shows that folic acid taken periconceptionally greatly reduces the risk of having a NTD affected child. This paper will explain the role that folate plays in the metabolism, specifically in synthesizing methionine. It will bring evidence to show that methionine is crucial for normal neural tube development. In addition, it will explore the genetic factor involved in folate metabolism and possible folate deficiency.

Atf4 Is An Oxidative Stress–Inducible, Prodeath Transcription Factor In Neurons In Vitro And In Vivo, Philipp Lange, Juan Chavez, John T. Pinto, Giovanni Coppola, Chiao-Wang Sun, Tim Townes, Rajiv Ratan

NYMC Faculty Publications

Oxidative stress is pathogenic in neurological diseases, including stroke. The identity of oxidative stress-inducible transcription factors and their role in propagating the death cascade are not well known. In an in vitro model of oxidative stress, the expression of the bZip transcription factor activating transcription factor 4 (ATF4) was induced by glutathione depletion and localized to the promoter of a putative death gene in neurons. Germline deletion of ATF4 resulted in a profound reduction in oxidative stress-induced gene expression and resistance to oxidative death. In neurons, ATF4 modulates an early, upstream event in the death pathway, as resistance to oxidative …

Urotensin Ii Modulates Rapid Eye Movement Sleep Through Activation Of Brainstem Cholinergic Neurons, Salvador Huitron-Resendiz, Morten P. Kristensen, Stephen L. Grupke, Christopher Tyler, Olivier Civelli, Christopher S. Leonard, Luis De Lecea

NYMC Faculty Publications

Urotensin II (UII) is a cyclic neuropeptide with strong vasoconstrictive activity in the peripheral vasculature. UII receptor mRNA is also expressed in the CNS, in particular in cholinergic neurons located in the mesopontine tegmental area, including the pedunculopontine tegmental (PPT) and lateral dorsal tegmental nuclei. This distribution suggests that the UII system is involved in functions regulated by acetylcholine, such as the sleep-wake cycle. Here, we tested the hypothesis that UII influences cholinergic PPT neuron activity and alters rapid eye movement (REM) sleep patterns in rats. Local administration of UII into the PPT nucleus increases REM sleep without inducing changes …

Specific Functions Of Synaptically Localized Potassium Channels In Synaptic Transmission At The Neocortical Gabaergic Fast-Spiking Cell Synapse, Ethan Goldberg, Shigeo Watanabe, Su Ying Chang, Rolf Joho, Z Josh Huang, Christopher S. Leonard, Bernardo Rudy

NYMC Faculty Publications

Potassium (K+) channel subunits of the Kv3 subfamily (Kv3.1-Kv3.4) display a positively shifted voltage dependence of activation and fast activation/deactivation kinetics when compared with other voltage-gated K+ channels, features that confer on Kv3 channels the ability to accelerate the repolarization of the action potential (AP) efficiently and specifically. In the cortex, the Kv3.1 and Kv3.2 proteins are expressed prominently in a subset of GABAergic interneurons known as fast-spiking (FS) cells and in fact are a significant determinant of the fast-spiking discharge pattern. However, in addition to expression at FS cell somata, Kv3.1 and Kv3.2 proteins also are expressed prominently at …

Direct And Indirect Excitation Of Laterodorsal Tegmental Neurons By Hypocretin/Orexin Peptides: Implications For Wakefulness And Narcolepsy, Sophie Burlet, Christopher Tyler, Christopher S. Leonard

NYMC Faculty Publications

Compelling evidence links the recently discovered hypothalamic peptides Hypocretin/Orexin (Hcrt/Orx) to rapid eye movement sleep (REM) control and the sleep disorder narcolepsy, yet how they influence sleep-related systems is not well understood. We investigated the action of Hcrt/Orx on mesopontine cholinergic (MPCh) neurons of the laterodorsal tegmental nucleus (LDT), a target group whose function is altered in canine narcolepsy and appears pivotal for normal REM and wakefulness. Extracellular recordings from mouse brainstem slices revealed that Hcrt/Orx evoked prolonged firing of LDT neurons. Whole-cell recordings revealed that Hcrt/Orx had actions on both presynaptic neurons and at postsynaptic sites. Hcrt/Orx produced an …

Impaired Fast-Spiking, Suppressed Cortical Inhibition, And Increased Susceptibility To Seizures In Mice Lacking Kv3.2 K+ Channel Proteins, David Lau, Eleazar Vega-Saenz De Miera, Diego Contreras, Alan Chow, Richard Paylor, Christopher S. Leonard, Bernardo Rudy

NYMC Faculty Publications

Voltage-gated K(+) channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to -10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one …