Lance W. Kreplick, M.D.
- Assistant Professor
- University of Illinois
- EHS Christ Hospital
- Oak Lawn, IL
Saponins Saponins are a class of polyphenols consisting of glycosides linked to a hydrophobic aglycone (sapogenin) erectile dysfunction drug therapy best buy zenegra, which may be triterpenoid or steroid erectile dysfunction after radical prostatectomy treatment options buy discount zenegra 100 mg online. Due to the importance of glucose to meet the energy requirements of the cells how young can erectile dysfunction start purchase generic zenegra from india, mammals have developed an advance mechanism to maintain the glucose level within a certain threshold in the blood during the fast and fed states erectile dysfunction 55 years old cheap zenegra 100mg free shipping. This mechanism involves the hormonal modulation of glucose production by the liver (during the fast state) or glucose uptake and utilization by the muscle and the peripheral tissues (during the fed state) erectile dysfunction hormones purchase zenegra 100mg overnight delivery. It is produced by the -cells of the pancreas in response to elevated blood glucose. In vitro and in vivo studies have shown that the release of insulin is stimulated by the exposure of the pancreatic islet to elevated glucose concentrations. An impairment in maintaining the blood glucose threshold leads to the multifactorial physiological state called hyperglycemia. Chronic exposure of -cells to fatty acid and glucose beyond the physiological concentrations (hyperglycemia and hyperlipidemia) causes glucolipotoxicity, which leads to a cascade of events resulting in -cell dysfunction and insulin resistance. Hyperglycemia-induced oxidative stress and diabetic complications Insulin secretion is highly connected to glucose regulation, glucose, therefore, poses as a principal and critical determinant of -cell functioning. Consequently, the glucose concentrations in the blood remain high and will result in an influx of glucose into insulinindependent tissues. Researches have grown over the years using phytochemicals in the development of new types of therapeutics for the treatment of diabetes and its complications. Inhibition of this process is crucial in the management of diabetes and its complications. There are evidences that the expressions of these transporters are increased in diabetic subjects, thus, increasing postprandial glucose and hyperglycemia. Delayed gastric emptying decreases postprandial glucose and, subsequently, hyperglycemia. Phytochemicals have been found to improve glucose uptake through various mechanisms. Gallic acid, sitosterol, and quercetin are bioactive compounds found in different parts of D. On the other hand, the liver utilizes glucose through glycolysis or stores it as glycogen when the blood glucose levels are elevated. Insulin, thus, increases the activity of glucokinase (hexokinase) and decreases the activity of key enzymes in the gluconeogenesis pathway. However, as hyperglycemia persists, it leads to a decline in -cell functioning as a result of -cell exhaustion and -cell demise. A recent report demonstrated the pancreatic -cell regeneration potential of the hexane extract of D. Polyphenols quench free radicals through numerous mechanisms, namely (1) through electron donating ability, (2) through proton donation, (3) by chelating metal ions, and (4) by improving endogenous antioxidant enzyme activity. Proton-donating mechanisms: the mechanism involving phenolic hydrogen as a proton-donating radical is as a result of the Glucose uptake and utilization Primarily, skeletal muscle, adipose tissue, and the liver play a dominant role in glucose utilization. Antioxidants and Pathology Conflict of interests 209 formation of a stable radical, usually by the presence of a O-dihydroxy structure in one of the polyphenol rings. The polyphenol radical is less reactive and stabilizes as a result of its ability to distribute the radicals all over the molecules. Improving endogenous antioxidant enzyme activity the activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, etc. Several studies have reported the ability of polyphenols to improve the activities of antioxidant enzymes in disease states. The significant increase in the activities of these enzymes indicates the antioxidative potential of D. These potentials are attributed to its phytochemical constituents, particularly polyphenols. However, more studies are required on the molecular mechanisms involved in its antioxidant and antidiabetic activity. Toxicological and pharmacological concerns on oxidative stress and related diseases. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Concentrated hot water-infusion of phragmanthera incana improves muscle glucose uptake, inhibits carbohydrate digesting enzymes and abates Fe21-induced oxidative stress in hepatic tissues. Stems extracts of tinospora cordifolia induces pancreatic regeneration, promotes insulin secretion and peripheral glucose uptake in streptozotocin diabetic rats. Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. Assessment of In vivo antioxidant properties of Dacryodes edulis and Ficus exasperata as anti-malaria plants. Nutritional composition and microbial spoilage of Dacryodes edulis fruits vended in Southern Nigeria. Evaluation of the polyphenol composition and antioxidant activity of African variety of Dacryodes edulis (G. Evaluation of the chemical composition of Dacryodes edulis and Raphia hookeri Mann and Wendl exudates used in herbal medicine in south eastern Nigeria. Phytochemical screening and medicinal potentials of the bark of Dacryodes edulis (G. Studies on Dacryodes edulis 1: phytochemical and medicinal principles of raw seeds. The phytochemical study and antibacterial activities of the seed extract of Dacryodes edulis (African Native Pear). Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease. In vitro antioxidant activity and phytochemical screening of methanol extracts of Ficus capensis and Dacryodes edulis leaves. Tannins: current knowledge of food sources, intake, bioavailability and biological effects. Important antinutrients in plant feedstuffs for aquaculture: an update on recent findings regarding responses in salmonids. Boerhaavia diffusa inhibits key enzymes linked to type 2 diabetes in vitro and in silico; and modulates abdominal glucose absorption and muscle glucose uptake ex vivo. New antimalarial hits from Dacryodes edulis (Burseraceae)-Part I: isolation, in vitro activity, in silico "druglikeness" and pharmacokinetic profiles. Increased -cell apoptosis prevents adaptive increase in -cell mass in mouse model of type 2 diabetes: evidence for role of islet amyloid formation rather than direct action of amyloid. Dissection of metabolic, vascular, and nerve conduction interrelationships in experimental diabetic neuropathy by cyclooxygenase inhibition and acetyl-L-carnitine administration. Effect of processing methods on the antioxidant properties and inhibition of -amylase and -glucosidase by African pear (Dacryodes edulis) fruit. Altered glucose carrier expression: mechanism of intestinal adaptation during streptozocin-induced diabetes in rats. Characteristics and composition of the pulp oil and cake of the African pear, Dacryodes edulis (G. Literature re Key words: Dacryodes edulis, Traditional use, Phytochemical, Pharmacological potentialities. Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production. Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. Cytotoxicity and free radical scavenging activities of hexane fractions of Nigeria specie of African pear (Dacryodes edulis). Effect of boiling on the phytochemical constituents and antioxidant properties of African pear Dacryodes edulis seeds in vitro. Antioxidant properties of phenolic compounds: H-atom versus electron transfer mechanism. Dietary polyphenols as antioxidants and anticancer agents: more questions than answers. Protective role of epigallocatechin gallate, a dietary antioxidant against oxidative stress in various diseases the subsequent damage. Imbalance in the redox state of the cells generates toxic effects via peroxides and free radicals production. Such toxic effects damage the integral cell components such as nucleic acids, lipids, and proteins. Thiols, ascorbic acid, or polyphenol molecules are among the various antioxidants that act as reducing agents by inhibiting the oxidation of many molecules by being self-oxidized. Among these, vitamin E is the main chainbreaking antioxidant of the cell membrane. In dietary supplements, antioxidants are widely used and studies are conducted to find out the protective role of dietary supplements against various types of diseases including coronary heart disease, cancer, immunological disorders, neurodegenerative disease, and even altitude sickness. Formed by radical reactions with cellular components such as lipids and nucleobases. Oxygen-centered radicals participate in lipid peroxidation reactions produced in the presence of oxygen either by radical addition across double bonds or hydrogen abstraction. Readily oxidizes protein constituents such as thiol groups, amino groups, and methionine. It forms peroxynitrous acid upon protonation, which subsequently forms hydroxyl radical and nitrogen dioxide through homolytic cleavage. Coenzyme Q Coenzyme Q (CoQ) is naturally found in humans with high levels in the liver, heart, and kidneys, etc. CoQ is a benzoquinone derivative and is localized at the mitochondrial respiratory chain along with some other internal membranes. CoQ is directly involved in the transportation of electrons in the respiratory chain and also couples it with oxidative phosphorylation. The apoferritin shell is formed by the association of 24 ferritin subunits, where each apoferritin molecule takes up iron atoms. However, the uricase enzyme acts as an inhibitor for uric acid, but researchers have reported that such enzymes (uricase) have been inactivated during the evolution of humans and apes. Previous studies have reported that high uric acid levels in blood protect from oxidative injury in neural, vascular, and cardiac cells. Ultimately, the heme is degraded for the reduction of biliverdin to bilirubin by the biliverdinreductase enzyme. Bile pigments as potent in vitro scavengers of free radicals are an important inducible antioxidant system that protects against various cellular stresses including oxidative damage. Bilirubin protects neurons against damages caused by H2O2 and also has a protective role against ischemic injury in isolated hearts. Vitamin C is a significant antioxidant due to the formation of relatively stable ascorbyl free radical by the donation of an electron. Protective role of epigallocatechin gallate, a dietary antioxidant against oxidative stress in various diseases target molecules. Many plant pigments including -Carotene and various other flavonoids have antioxidant property12 and plant phenols are seen to inhibit lipid peroxidation and lipoxygenase enzymes (in vitro). Epigallocatechin gallate the leaves from Camellia sinensis are used in making black or green tea. Polyphenols perform the neutralization of free radicals and, hence, decrease the inflammation and inhibit the development of tumors. Study population 82 patients with early atherosclerosis 42 patients with coronary artery disease 25 male patients with wildtype transthyretin amyloid cardiomyopathy Dose 30 mL supplemented with olive oil 300 mg initial dose followed by 150 mg for 2 weeks 600 mg for 12 months Effect Improved endothelial function by reducing the number of leukocytes. Induced cytotoxicity of human sebocytes via apoptosis and decreased the viability of P. Epigallocatechin gallate and cancer Oncogenesis is considered as a composite and several-step procedure where modifications take place at the cellular and molecular levels. Protective role of epigallocatechin gallate, a dietary antioxidant against oxidative stress in various diseases progression stage, known as the neoplastic transformation stage where uncontrolled growth leads to tumor formation. This stage involves the formation of an abnormal mass of tissue (neoplastic) from the premalignant cells with improved potential of metastasis, invasiveness, and angiogenesis. Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Heme oxygenase-1-derived bilirubin ameliorates postischemic myocardial dysfunction. Green tea and its polyphenolic catechins: medicinal uses in cancer and noncancer applications. Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia reperfusion injury in rats. Green tea epigallocatechin-3-gallate attenuates Porphyromonas gingivalisinduced atherosclerosis. Epigallocatechin-3-gallate prevents cardiac apoptosis by modulating the intrinsic apoptotic pathway in isoproterenol-induced myocardial infarction. Polyphenol (-)-epigallocatechin gallate-induced cardioprotection may attenuate ischemia-reperfusion injury through adenosine receptor activation: a preliminary study. Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis. Systematic review of green tea epigallocatechin gallate in reducing lowdensity lipoprotein cholesterol levels of humans.
We know that redox signaling is fundamental in preserving cell and microorganism survival and erectile dysfunction medication ratings cheap zenegra 100mg on-line, importantly erectile dysfunction vitamins order zenegra in india, many diseases have been linked to loss of signaling control impotence female purchase zenegra canada. Thus it is a second messenger that impotence yoga postures discount zenegra 100mg with visa, depending on the oxidation degree erectile dysfunction vitamin deficiency buy zenegra 100 mg on line, can be reversibly or irreversibly converted to persulfides and sulfinic acids, respectively. SoxR acts also by controlling the expression of antioxidant enzymes, but it is triggered by enhanced O2 concen2 tration (Table 8. Its activation by the pathogens induces adaptive responses against immune response of the host. Regulates the expression of antioxidant enzymes after its activation by the generation of reactive species. Its oxidation products such as sulfenic acids trigger the activation of redox-related transcription factors. Furthermore, their function in pathogens and host organisms on the grounds of disease onset is described. Oxidative Stress and Pathology Redox signaling as a determinant for pathogen thriving in the context of oxidative stress 89 considered by researchers of different fields. One of them, probably the most sophisticated, is the escape from the phagocyte toward the cytosol of the host. Thus someone could aptly consider that antioxidant administration is a practice that does not help the host to confront pathogens. However, this does not always hold true since there is experimental evidence that antioxidants may be proven effective against microbe invasion in some cases. Redox signaling as a determinant for pathogen thriving in the context of oxidative stress In this section, a few examples with respect to the ability of some bacteria to diminish host defense by adopting very clever mechanisms are presented. An interesting example is that of Listeria monocytogenes, which causes listeriosis. During inflammation followed by the bacterial invasion, phagocyte activity induces the production of the oxidizing agent tetrathionate by thiosulfate. To this end, and due to DtxR, Corynebacterium diphtheriae (the bacterium that causes diphtheria) secrets its toxin in an iron-free environment as is the case for Fur that regulates alpha toxin and leukotoxin expression by Staphylococcus aureus (responsible for several serious infections). Although there are hundreds of studies backing up this aspect, only a few of them will be referred to in this section. The author has no intention to underestimate the significance of these groundbreaking observations. Nevertheless, he believes that the findings pointing to the novel point of view fit better to the aim of the chapter. Redox signaling, through various representatives, plays key roles in killing microorganisms. Its biological basis has not been fully elucidated, but it appears that it applies to a wide spectrum of I. Phagocytosis is the biological process during which the infected host eliminates pathogenic microorganisms. This figure summarizes a few fundamental, redox-related mechanisms leading to the decrease of the pathogen burden. Specifically, calprotectin that is secreted by phagocytes sequesters zinc, a process that reduces inflammation and, hence, increases pathogen burden. It seems that resveratrol, which is a potent naturally occurring antioxidant, enhances replication and, thus, the virulence of hepatitis C virus. Particularly, the cases of Mycobacterium abscessus,27 Bacillus anthracis,28 Trypanosoma cruzi,29 P. The examples point out that there are specific redox signaling pathways assisting pathogens to overcome the detrimental outcome of host-induced antioxidant generation or inflammatory response. Although in our case there is definitely a countermarch to the dominating point of view, it is not sure yet that we are in front of a paradigm shift as proposed by Kuhn. Therefore the change in the current notion is more conservatively characterized by the author as a "perception shift. In this line of the intriguing dual role of antioxidants Over the past 15 years, there has been a shift in the established notion that antioxidants are mainly beneficial for human health. This idea has gained many adherents recently due to the multitude of relevant findings. However, in this chapter this phenomenon is not characterized as a paradigm shift since this is a highly specific term with especial traits described by the eminent science historian and philosopher Thomas Kuhn. Alternatively, the term "perception shift" is adopted by the author because he believes that there is not enough evidence to do otherwise. Still, it appears that we are in the middle of a process that could potentially alter the opinion of researchers about the biology of infections and, thus, lead to the discovery of novel therapeutic approaches. The administration or depletion of antioxidants and (pro)oxidants, at least on the basis of the currently available data, does not seem to act against all pathogenic microorganisms in the same manner. The most interesting idea that has emerged stipulates that antioxidants are effective under a personalized regimen. In lay terms this means that antioxidants act differently when they are administered in individuals that suffer from deficiencies in specific intrinsic antioxidants,49 and it has been implied that such individuals constitute the most suitable cohort for monitoring the antioxidant activity of diverse compounds. It is noteworthy that the vast amount of experimental data have been produced using in vitro models and clinical approaches are missing. Therefore the following question arises: What will be the paradigm/perception if we study the activity of antibiotics following a real infection inside the human body Future perspectives in therapy against pathogens In this article, the association of the basic ideas of redox biology with the defense and the putative therapy against pathogenic microorganisms was presented and discussed. Therefore therapeutic approaches need to be adapted appropriately by taking into account the perception shift observed in the field. Regarding redox-related therapeutic regimens, it is important to target specific signaling pathways with known participation in pathogen elimination and to adopt the correct biomarkers in order to monitor the outcome of medicines on infectious diseases. This figure illustrates the controversial role of antioxidant administration on pathogen burden. It is evident that specific antioxidant compounds are beneficial against infection induced by some microorganisms, whereas others seem to be ineffective, or even harmful, for the host. Thus due to lack of consistency in the experimental data there is no possibility to generalize regarding the putative therapy of infections on the grounds of antioxidant supplements. Redox signaling and antioxidant defense in pathogenic microorganisms: a link to disease and putative therapy be much easier to develop the proper medicine and to administer it under the most effective regimen. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Activation of the OxyR transcription factor by reversible disulfide bond formation. Antimicrobial strategies centered around reactive oxygen species-bactericidal antibiotics, photodynamic therapy, and beyond. The phagocytosis-associated respiratory burst in human monocytes is associated with increased uptake of glutathione. Applications to other areas of pathology Redox biology has been a rapidly expanding field over the past few decades. Therefore an in-depth study could potentially provide useful information about the development of novel therapeutic approaches. Following a similar practice with respect to research in the field of pathology, the etiology of several redoxrelated diseases could be more easily revealed by investigating the biological background of redox signaling pathways. Toward this research direction, the selection of the appropriate biomarkers should gain much attention because, ideally, they need to form a network with common functional and structural traits in order to have enhanced translational potency. This practice aids the monitoring of disease onset and the adoption of proper therapeutic regimens. An antioxidant resveratrol significantly enhanced replication of hepatitis C virus. Trypanosoma cruzi response to the oxidative stress generated by hydrogen peroxide. Roles of the host oxidative immune response and bacterial antioxidant rubrerythrin during Porphyromonas gingivalis infection. Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. The rat closely mimics oxidative stress and inflammation in humans after exercise but not after exercise combined with vitamin C administration. The antioxidant effects of a polyphenol-rich grape pomace extract in vitro do not correspond in vivo using exercise as an oxidant stimulus. Flavonoid glycosides isolated from unique legume plant extracts as novel inhibitors of xanthine oxidase. Effects of Greek legume plant extracts on xanthine oxidase, catalase and superoxide dismutase activities. A battery of translational biomarkers for the assessment of the in vitro and in vivo antioxidant action of plant polyphenolic compounds: the biomarker issue. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. Dietary oxidative stress and antioxidant defense with an emphasis on plant extract administration. Effects of xanthine oxidase inhibition on oxidative stress and swimming performance in rats. Differential effects of xanthine oxidase inhibition and exercise on albumin concentration in rat tissues. Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats. Oxidation of the guanine nucleotide pool underlies cell death by bactericidal antibiotics. These lesions occur principally in large and medium-sized arteries and can lead to ischemia of the heart, brain, or extremities, resulting in infarction. In fact, the earliest type of lesion, called fatty streak, which is common in infants and young children, is a pure inflammatory lesion. Monocytes are then transformed into macrophages and further activated by encounters with pathogen-associated molecular patterns, damage-associated molecular patterns, and various proinflammatory cytokines. It is mainly secreted by the liver, though local synthesis occurs in several tissues. Macrophages secrete a host of proinflammatory cytokines that lead to further recruitment of monocytes. Finally, foam cells together with activated endothelial cells secrete growth factors and metalloproteinases that degrade extracellular matrix and fragilize the atherogenic plaque. Interestingly, these alterations were reversed after 6-month treatment with metformin. Nevertheless, despite the abundant literature on this topic, the evidence regarding pediatric populations remains scarce. Neaton, Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded Relationship of baseline serum cholesterol levels in 3 large cohorts of younger men to long-term coronary, cardiovascular, and all-cause mortality and to longevity. Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (The Bogalusa Heart Study). Accumulation of extracellular cholesterol-rich liposomes in the arterial intima and cardiac valves of the hyperlipidemic rabbit. Tracking of serum lipids and lipoproteins from childhood to adulthood: the Bogalusa Heart Study. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults: the Bogalusa Heart Study. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents; National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Proatherosclerotic events: pathobiochemical changes occurring in the arterial wall before monocyte migration. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Lipoprotein modification and macrophage uptake: role of pathologic cholesterol transport in atherogenesis. Multiple substrates for paraoxonase-1 during oxidation of phosphatidylcholine by peroxynitrite. Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes. Paraoxonase-1 deficiency in mice predisposes to vascular inflammation, oxidative stress, and thrombogenicity in the absence of hyperlipidemia. Human paraoxonase gene cluster transgenic overexpression represses atherogenesis and promotes atherosclerotic plaque stability in ApoE-null mice. Quantitative assessment of the influence of paraoxonase 1 activity and coronary heart disease risk. Paraoxonase-1 does not reduce or modify oxidation of phospholipids by peroxynitrite. Serum paraoxonase-1 activity in children: the effects of obesity and insulin resistance.
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These changes in electrical properties are tightly correlated to very specific electrophysiological brain patterns erectile dysfunction treatment homeveda buy generic zenegra 100 mg line. At early stages impotence guilt 100 mg zenegra mastercard, the lack of robust synaptic connectivity necessary for network activity is counterbalanced by the high intrinsic neuronal excitability erectile dysfunction pills non prescription order 100mg zenegra free shipping. It has been proposed that the recurrent coactivation of cellular assemblies may promote growth erectile dysfunction pump hcpc buy zenegra on line amex, wiring erectile dysfunction causes mnemonic zenegra 100mg on-line, and more generally, plasticity (Leinekugel, 2003). Theta oscillations consist of periodic fluctuations of the hippocampal cell membrane potential in the 7e12 Hz range. It has recently been shown that the firing pattern of the neural assembly recorded during the exploratory period can also occur before the same exploratory period, a phenomenon known as "preplay" (Dragoi and Tonegawa, 2011). During movement, hippocampal theta oscillations are accompanied by the activities of place cells, head direction cells, and grid cells. It has been hypothesized that the activity of place cells, head direction cells, and grid cells is necessary to construct a cognitive representation of the surrounding environment. A rudimentary map of space is already present at P18 when the pup explores an open environment outside the nest for the first time (Langston et al. Head direction cells display adultlike properties from the beginning at P11, before eye opening (Bjerknes et al. Place cells are also present but develop more gradually, with grid cells showing the slowest development. The hippocampus is extensively interconnected with multiple wider networks, associated with emotional or spatial aspects. The power and frequency of theta oscillations are low at P16, reaching adult levels by P26. Pharmacological inactivation of the cholinergic cells of the medial septum increases the amplitude of postnatal developmental theta bursts in the hippocampus (Janiesch et al. These changes in electrical properties are paralleled by the maturation of the dendritic arborization and interneurons. As we have briefly surveyed here, cell populations are being further defined in terms of molecular, anatomic, and physiological features; and progress is being made on how these are grouped in functional assemblies in adult. A key issue is how these microcircuits vary within and across hippocampal subdivisions and how these interact under task- and stage-specific conditions. Developmental timelines are particularly important as informing behavioral stages and network dynamics across postnatal development. Moreover, new data may be expected from probing how developmental fates and transcriptomes influence activity driven features of the neural organization. Fundamentally, the hippocampal subdivisions present as a tapestry of multiple, partially overlapping circuits, and we can look forward with confidence to an abundance of fascinating new results. An analysis of entorhinal cortex projections to the dentate gyrus, Hippocampus, and subiculum of the neonatal macaque monkey. Human and monkey fetal brain development of the supramammillary-hippocampal projections: a system involved in the regulation of theta activity. Developmental emergence of hippocampal fast-field "ripple" oscillations in the behaving rat pups. Development of theta rhythmicity in entorhinal stellate cells of the juvenile rat. Hippocampal sharp wave-ripple: a cognitive biomarker for episodic memory and planning. Development of the entorhino-hippocampal projection: guidance by Cajal-Retzius cell axons. Temporally matched subpopulations of selectively interconnected principal neurons in the hippocampus. Functional imaging of hippocampal place cells at cellular resolution during virtual navigation. Eary- and late-born parvalbumin basket cell subpopulations exhibiting distinct regulation and roles in learning. Developmental expression and functional characterization of the potassium-channel subunit Kv3. Thalamic and entorhinal network activity differently modulates the functional development of prefrontalehippocampal interactions. A novel pyramidal cell type promotes sharp-wave synchronization in the hippocampus. Zinc-enriched amygdalo- and hippocampo-cortical connections to the inferotemporal cortices in macaque monkey. Supramammillary nucleus modulates spike-time coordination in the prefrontal-thalamo-hippocampal circuit during navigation. Building hippocampal circuits to learn and remember: insights into the development of human memory. Parvalbumin-positive basket cells differentiate among hippocampal pyramidal cells. Differential expression and cell-type specificity of perineuronal nets in Hippocampus, medial entorhinal cortex, and visual cortex examined in the rat and mouse. The entorhino-septo-supramammillary nucleus connection in the rat: morphological basis of a feedback mechanism regulating hippocampal theta rhythm. Morphologic and electrophysiologic maturation in developing dentate gyrus granule cells. Parvalbumin and somatostatin interneurons control different Space- Coding networks in the medial entorhinal cortex. Convergence of unimodal and polymodal sensory input to the entorhinal cortex in the fascicularis monkey. Electrophysiological characterization of granule cells in the dentate gyrus immediately after birth. Optogenetic activation of cajal-retzius cells reveals their glutamatergic output and a novel feedforward circuit in the developing mouse hippocampus. Structural development and dorsoventral maturation of the medial entorhinal cortex. Dendritic growth and regression in rat dentate granule cells during late postnatal development. Postnatal development of the light and electron microscopic features of basket cells in the hippocampal dentate gyrus of the rat. Organization and development of hippocampal circuits Chapter 9 219 Slomianka, L. Postnatal development of zinc-containing cells and neuropil in the hippocampal region of the mouse. Development of entorhinal, commissural, and Septa1 connections studied with the lipophilic tracer DiI. A blueprint for the spatiotemporal origins of mouse hippocampal interneuron diversity. Emergence of coordinated activity in the developing entorhinal-hippocampal network. The hippocampus in depth: a sublayer-specific perspective of entorhinal-hippocampal function. The anatomy of memory: an interactive overview of the parahippocampal hippocampal network. Postnatal development of the hyperpolarization-activated excitatory current Ih in mouse hippocampal pyramidal neurons. Development of early-born c-aminobutyric acid hub neurons in mouse Hippocampus from embryogenesis to adulthood. Interneurons differentially contribute to spontaneous network activity in the developing Hippocampus dependent on their embryonic lineage. Distinct lineage-dependent structural and functional organization of the hippocampus. Normal behavioral functions attributed to the basal ganglia are more wide ranging. This is due to the fact that as most cortical areas provide inputs to the basal ganglia, many behaviors involving the cerebral cortex are affected by the basal ganglia. Inputs from the cerebral cortex targeting the input nucleus of the basal ganglia, the striatum, are organized in parallel loops through the basal ganglia based on the cortical areas from which those inputs arise, which affect distinct behaviors (Alexander et al. The distinct behaviors these loops govern include motor learning, habit formation, and the selection of actions based on desirable outcomes (Balleine et al. Prefrontal and cingulate cortical areas project to the dorsal medial striatum, which is implicated in motor learning coding actioneoutcome associations. Sensorimotor cortical areas project to the dorsolateral striatum, which is implicated in habit formation that code stimuluseresponse associations (Yin et al. For example, the frontal cortical areas are involved in the planning and execution of movement and include direct corticospinal projections as well as input to basal ganglia. Understanding the role of the basal ganglia in behavior depends on determining the computations that are performed on cortical information through its neuroanatomical circuits. The major input nucleus is the striatum, which in the mouse consists of the dorsal striatum (also referred to as the caudateeputamen) and the ventral striatum, which includes the nucleus accumbens. The major glutamatergic excitatory input to the striatum arises from layer 5 and to a lesser extent from layer 2/3 of virtually all neocortical areas, from allocortical areas, and from the basolateral amygdala. Two main subtypes of projection neurons in the striatum give rise to direct and indirect pathways. Neocortical areas project mainly to the dorsal striatum, whereas allocortical areas project to the ventral striatum. Glutamatergic excitatory inputs to the striatum also arise from the intralaminar thalamic nuclear complex, including the parafascicular nucleus. These nuclei provide tonic inhibitory input to thalamic nuclei including the ventromedial and paralamellar mediodorsal nuclei, which project to frontal motor related areas, to the intermediate layers of the superior colliculus, and to the pedunculopontine nucleus. The most important of these is the dense dopaminergic projection from the midbrain dopamine neurons to the striatum, along with a sparser serotonergic input from the dorsal raphe and noradrenergic input from the locus coeruleus. Consequently, the information that striatal Basal ganglia circuits Chapter 10 223 projection neurons process within the circuits of the basal ganglia is largely determined by the organization of activity of corticostriatal (and thalamostriatal) inputs. Corticostriatal projections arise mainly from layer 5 and to a smaller degree from layer 2/3 pyramidal neurons. There are two main subtypes of corticostriatal neurons (Cowan and Wilson, 1994; Wilson, 1987; Wise and Jones, 1977; Zheng and Wilson, 2002; Shepherd, 2013). The somata of these cells are located in layer 2/3 and for the most part in upper layer 5. The somata of these cells are located primarily in lower parts of layer 5 (Kita and Kita, 2012). Corticostriatal projections are organized in a general topographic manner such that the spatial relationships of the areas of the cerebral cortex are maintained in the projection of neurons in these areas to the striatum (Carman et al. However, these projections do not map precisely in that the projections from individual cortical areas are distributed broadly with considerable overlap of projections from different cortical areas. The patterns of overlap of corticostriatal projections are critical in determining how information from the cortex is integrated through basal ganglia circuits. A long-standing model is that cortical areas that are interconnected with each other provide converging inputs to the striatum (Alexander et al. In their model based on data from primates, corticobasal ganglia circuits include parallel motor, oculomotor, and prefrontal pathways. Similar parallel circuits have been identified in the mouse that include distinct parallel sensorimotor and association pathways that target different topographically related regions of the striatum (Hintiryan et al. The organization of corticostriatal projections into parallel functional circuits related to the mapping of interconnected cortical areas into the striatum underlies the functional roles of different areas of the striatum. For example, the dorsal medial striatum, which receives inputs from prefrontal and cingulate cortical areas, is implicated in motor learning coding of actioneoutcome associations. The dorsolateral striatum, which receives input from sensorimotor cortical areas, is implicated in habit formation that code stimuluseresponse associations (Yin et al. While the general principles governing the organization of cortical input to striatal regions are related to the topographic mapping of the organization of corticocortical connections of functionally related areas, the organization of these inputs is more complex due to differences in the specific projections from different cortical areas and of subtypes of corticostriatal neurons within these areas. The precision of the topographic projections from the cortex to the striatum varies dependent on the cortical origin (Hooks et al. In general, the topographic relationship between different cortical areas is maintained in their projections to the striatum such that lateral cortical areas project into the lateral striatum compared with medial areas. The projections from specific cortical areas, such as the somatosensory and motor areas, are each organized topographically. For example, the somatosensory cortex is organized somatotopically with distinct mouth, barrel field, and upper and lower limb regions, and the projections of these areas to the striatum maintain their somatotopic organization. Similarly, projections from primary and secondary motor areas each also project in a topographic manner. The topographic organization of cortical projections is also maintained in projections to the thalamus, superior colliculus, and pontine nuclei. This type of mapping reveals the topographic organization of the dominant projections from discrete cortical areas. However, the projections from each discrete cortical area distribute over a larger domain, overlapping with projections from other cortical areas. Analysis of the overlap from different cortical injections within functional cortical areas dependent on the distance between the injection sites provides a measure of the precision of their somatotopic organization within the striatum. Such analysis demonstrates a progression of decreasing somatotopic precision from primary somatosensory cortex to primary and then secondary motor cortical areas (Hooks et al.
This term conjures up images of the boss who is in control of the various aspects of a business impotence definition order zenegra pills in toronto. The prefrontal cortex is an important neuroanatomical structure for executive functions erectile dysfunction is often associated with quizlet buy generic zenegra 100mg line. Cognitive-Communicative Disorders 313 Creativity: having the imagination and ability to create things Shifting cognitive set: shifting thinking from one set of rules to another Mental flexibility: handling different situations in different ways otc erectile dysfunction pills walgreens cheap zenegra 100mg without prescription, especially to respond effectively to new erectile dysfunction ear buy discount zenegra on line, complex erectile dysfunction caused by herpes generic zenegra 100mg fast delivery, and problematic situations. These people will also sometimes struggle with being socially appropriate, which can lead to social isolation. Cognitive-Communicative Disorders Lastly, Blumenfeld (2010) defines order as "the capacity to correctly perform sequencing tasks and a variety of other cognitive operations" (p. Order involves the following: Right Hemisphere Disorder Historically, researchers in neuroscience have been more interested in left hemisphere function than right hemisphere function. It was thought that the right hemisphere was of little importance to communication and, thus, was not important overall. Visual spatial deficits related to the right hemisphere were reported in the 1940s followed by an interest in communication problems in the 1960s and 1970s. Public awareness of right hemisphere damage also increased in the 1970s and 1980s through two famous cases. He returned to the bench after his stroke, but observers of the Supreme Court noticed his communication rambled on and he often asked irrelevant questions; moreover, he denied having deficits, even his left hemiparesis. Damage was done to the right hemisphere, but Brady was not like Douglas in his symptomology. Brady is remembered for the federal gun control legislation that bore his name-the Brady Handgun Violence Prevention Act-enacted in 1993 that mandated federal background checks and a 5-day waiting period for gun purchases. For example, under restraint, one would need foresight to see potential obstacles in attaining a goal as well as perseverance and concentration. Initiative might contribute drive and mental flexibility if obstacles are encountered. Lastly, order would add planning, organization, and sequencing in setting and attaining goals. Signs of executive function problems are evident in the three categories presented earlier-restraint, initiative, and order. More specifically, those with executive function problems will have trouble planning projects and projecting the time needed to complete them, 314 Chapter 14 the Neurology of Cognition into linguistic and extralinguistic deficits. Linguistic deficits include rambling speech, poor coherence in producing and comprehending conversation and narratives, poor comprehension of abstract language and humor, and poor pragmatic skills. Extralinguistic deficits include aprosody and a lack of producing and interpreting emotion. Logic would dictate that improvements in attention would result in improvements in episodic memory in this population. Under restraint, they may demonstrate poor judgment and lack foresight in how their actions affect others. These deficits are classified under order, specifically involving organization, sequencing, and temporal order. Cognitive-Communicative Disorders 315 One day a woman was doing dishes in the kitchen. Because of her daydreaming, she did not realize that the water was overflowing from the sink onto the floor. As Mikey begins to take a cookie, he loses his balance on the stool and is about to fall onto the floor. Mikey will have to apologize to his mom and be disciplined, but then all will be forgiven. There are even times the patient misperceives elements in the picture, like seeing a hat instead of a plate. This focus on the details at the expense of the whole picture can be a significant problem in telling stories to others or in having coherent and cohesive conversations. These problems can lead to vocational and educational issues, because a lack of attention impairs both memory and executive functions, and slowed thinking makes these pursuits frustrating. Retrograde amnesia is a loss of some or all memory before the brain injury, while anterograde amnesia is a loss of some or all memory between the brain injury and the present. Anterograde amnesia is the loss of the ability to make new memories post-accident, like in the case of H. These struggles can impair all three main areas of executive function (restraint, initiative, and order). In terms of restraint, patients will sometimes have difficulty inhibiting socially inappropriate behaviors. For example, they may make sexually explicit statements or inordinately use foul language. Initiative and order deficits can especially impair their ability to set, attain, and evaluate progress on goals. The injury sustained can involve penetration of the skull (open head injury) or the brain coming in contact with the inside of the skull (closed head injury). During the second Gulf War, many soldiers died or were injured by improvised explosive devices. The secondary level of damage results from flying shrapnel, causing open head injuries. The tertiary level of damage occurs when soldiers are knocked off their feet by the explosion. They may suffer a closed head injury due to hitting their head on the group or on an object. Lastly, quaternary levels of damage involve anything not covered under the categories of primary through tertiary levels of damage. At the end of the day, most will think back and assess how well these goals were achieved and what is left to be done. Some of this shrinkage is due to neuronal death, but most of it is due to myelin breaking down, the thinning of dendrites, and the loss of synapses. Webster had suffered from amnesia, depression, and executive function issues for years, and Dr. There has even been a big-budget movie starring Will Smith called Concussion that dramatizes Dr. Top: Whole brain section from a 65-year-old control subject showing no abnormal tau protein deposition. Bottom: Microscopic section showing numerous tau-containing neurofibrillary tangles in the brain. Bottom: Microscopic section showing abundant tau-containing neurofibrillary tangles. Dementia is a group of progressive neurological disorders that lead to cognitive decline. Patients with this logopenic variant can be both fluent when not having word retrieval problems and nonfluent when experiencing anomia. These plaques are toxic to neural cells, causing inflammation and impairing their function. The area most affected is the hippocampus and entorhinal area, critical structures for declarative memory. This impairment can show up practically in the inability to resist distraction from competing stimuli. This condition is genetic, following an autosomaldominant inheritance pattern in which children of those affected have a 50% chance of inheriting the disease. Initiative to communicate can wain as the disease becomes worse, and when they do speak, their thoughts can lack order and be confusing to the listener. As a university student, your cognitive abilities should be working at a high level. The different forms of attention mentioned in this chapter are important for class lectures, reading, and other activities. Memory is critical for learning new information (declarative memory) and in learning new skills (nondeclarative memory). Executive functions are also essential for the many exams, quizzes, papers, and projects. In many ways, setting and achieving realistic goals is as important as acquiring knowledge and skills. The information that should have been learned is listed below each learning objective. The types of attention include focused, sustained, selective, alternating, and divided. Long-term memory includes declarative or explicit memory (includes episodic and semantic) and nondeclarative or implicit memory (includes procedural memory). The learner will describe the neural basis of attention, memory, and executive functions. By comparison, in Huntington disease the basal ganglia degenerate, resulting in nondeclarative memory issues. Draw an illustration that would explain the different types of attention discussed in this chapter. List the different types of attention and give illustrations of how you use these in everyday life. List the neurological structures associated with attention, memory, and executive functions. Though he could talk fluently and understand what people said to him, he now appeared to ramble on in conversation. Once a gripping storyteller, he now verbally wandered in telling stories, perseverating on details and not telling the overall story arc. In conversation, he is pragmatically awkward as shown by dominating conversations, ignoring hints and request from others for repairs, and lacking an ability to effectively use facial expression and emotion with others. In addition to all this, his wife reports he denies having any problems at all after his stroke. Think about the following cognitive processes: perceiving, remembering, comprehending, judging, and reasoning. Think about your life as a student and give concrete examples of how you use these processes on a daily basis. Think about executive functions and describe how you engage in goal-directed behavior on 4. Test your divided attention by attempting to read and talk to a friend at the same time. Write a case of someone who has suffered a traumatic brain injury who now has executive function and memory problems. Stroop effects in persons with traumatic brain injury: Selective attention, speed of processing, or color-naming Prevalence of dementia in the United States: the aging, demographics, and memory study. What clinical disorders tell us about the neural control of saccadic eye movements. Remediation of memory disorders: Experimental evaluation of the spacedretrieval technique. The "myth" of media multitasking: Reciprocal dynamics of media multitasking, personal needs, and gratifications. Memory impairment following right hemisphere stroke: A comparative meta-analytic and narrative review. Right hemisphere dominance for attention: the mechanism underlying hemispheric asymmetries of inattention (neglect). Expanding retrieval practice promotes short-term retention, but equally spaced retrieval enhances long-term retention. Functional disability and rehabilitation outcome in right hemisphere damaged patients with and without unilateral spatial neglect. Relearning the names of things: the spaced-retrieval intervention implemented by a caregiver. Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football. First, our patients are emotional beings and will express emotion to us at some point in time. Second, some of our patients, like those with autism, will have difficulty with their emotions or reading the emotions of others. Thus, the topic of emotion is a highly relevant topic for speech-language pathologists and audiologists, especially as it intersects with counseling patients and their caregivers. The learner will list and describe neural structures involved with emotional processing. The learner will describe the connection between patient emotions, like fear, and the need for counseling in speechlanguage pathology and audiology. Vulcans, a humanoid species, have learned to suppress their emotions over many centuries in order to live by logic. One of the fun parts of the series is to see Vulcans begin to get in touch with their suppressed emotions and become more like humans. Spock, who is part human and part Vulcan, is one of the best examples of this struggle.
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