By A. Pavel. Western Michigan University. 2019.

Resistance skills programs This approach postulates that drug use is due to direct or indirect social influences exerted by the media or the peer group (e cheap nizagara online visa. It argues that sometimes adolescents do not have certain skills to cope with social situations that promote the use of psychoactive substances order nizagara 50mg. Apart from these types of skills buy 50mg nizagara overnight delivery, they usually include the main persuasion techniques used in advertising and by the media order 100mg nizagara overnight delivery, along with modules that correct the perception that the majority of people use drugs. Therefore, the objective of school-based programs that form part of this approach is that subjects learn to avoid high risk situations 17 School-based Drug Use Prevention and/or acquire the knowledge, confidence and skills to deal with social pressure. Over the past two decades, numerous studies have been conducted to assess the efficacy of this approach. Broadly speaking, research supports a small but positive effect of programs based on resistance skills training against the consumption of tobacco, alcohol and marijuana. However, data from studies evaluating the long-term effects of such programs indicate that these effects gradually decrease over time (Flay et al, 1989; Murray, Piere, Luepker and Pallonen, 1989). Skills improvement programs Skills improvement programs consider drug use to be a socially learned behavior, resulting from the interaction of multiple factors and produced by deficiencies in several areas. Therefore, the main aim pursued by these programs is the development of the skills necessary to prevent the use of substances as compensation for said deficiencies or as a coping strategy. This approach, in addition to including components of the previous approach, places emphasis on the acquisition of general skills (personal and social) that have a broader application than the specific application of refusing drug offers. Nevertheless, the personal and social skills training focuses specifically on drug use, although the repertoire of acquired skills is useful in many life situations. With regard to the programs that have been specifically developed to prevent drug use, some studies have found effects on drug use behaviors (Coggans, Cheyne and McKellar 2003; Epstein, Botvin, Diaz, Toth and Schinke, 1995; Faggiano et al. Multi-component programs A large majority of school-based prevention programs include more than one type of intervention. In this sense, the commonly called multi-component programs usually combine curricular interventions in schools with more extensive environmental changes, such as parent training, media campaigns and/or broad community interventions. However, very few efforts have been made to evaluate which features are responsible for the efficacy of these multi-component programs (Allott, Parson and Leonard, 1999; Canning, Millward, Raj and Warm, 2004; Flay 2000). In addition, due to their complexity, such programs are more difficult to implement and evaluate than those focused on a single area. Therefore, they run the risk of being diffused and difficult to sustain over the long term, since they require the cooperation of a large number of subjects and/or groups. Similarly, the results must be treated with caution, since the studies from which they are drawn have several methodological problems. When estimating the efficacy separately for each of the added features, differential effects are not found and/or they are shown to be less efficacious than school-based programs. Programs based on scientific evidence Currently, school-based prevention programs are characterized by being based on evidence provided by scientific data, building on the learning of various types of skills. All the efforts invested in prevention focus on the evaluation of programs, strategies and preventive activities by means of increasingly rigorous research on the forms of intervention. Evaluations are conducted in order to be able to discern what works from what does not, and consequently, that which is appropriate to implement and that which is not for our preventive purposes. Thus, the majority of up-to-date programs focus on generating significant changes in two variables types: mediating variables (e. Table 1 illustrates a summary of the chronological order that the development of prevention programs has followed. Years Dominant Preventive Programs 19 School-based Drug Use Prevention Knowledge-based 1960-70 Based on providing information about drug use and its effects. Just as the content domain distinguishes one type of program from another, the way in which they are applied also differentiates them from each other. Studies suggest that the most effective teaching approaches are interactive (Cuijpers, 2002; Flay, 2000; Maiwald and Reese, 2000; McBride, Farringdon, Midford and Phillips, 2001; Shin, 2001; Shope, Elliot, Raghunathan and Waller, 2001; Skara and Sussman, 2003; Tobler et al. Since interactive programs provide 20 Mónica Gázquez Pertusa, José Antonio García del Castillo, Diana Serban and Diana Bolanu opportunities for contact, communication, and the exchange of ideas among participants, they stimulate the learning of drug refusal skills. Thus, receiving feedback and constructive criticism in an atmosphere of trust allow students to practice the refusal skills that they have just learned. That is, the programs that reduced drug use employed interactive methods, while other programs used non-interactive methods. Similarly, the results of these studies show that programs that emphasize knowledge and affective content tend to utilize non-interactive methods. On the other hand, programs that stress knowledge with refusal skills and knowledge along with refusal and generic skills tend to utilize interactive methods. In conclusion, the results of these meta-analysis studies indicate that interactive prevention programs and social influence prevention programs outperform non-interactive programs that focus on knowledge alone. Likewise, the existence of a good cost-effectiveness relationship of such projects carried out in the school has been proven (Caulkins, Pacula, Paddock and Chiesa, 2004). In the case of drug dependencies, the main objective of a program is to prevent, reduce or delay the onset and associated consequences of the abuse and consumption behavior of various drugs. However, and depending on the target group, the previous general objective has to be broken down into clearly defined objectives. In turn, each specific objective must be linked to specific activities to be carried out for its attainment. In that regard, these activities, strategies and techniques are the elements that make a preventive program achieve its objectives (i. Nevertheless, it should be noted, as we have seen in Unit 2, the potential of these elements depends largely on the methodology used to apply them. Information transmission Although, as previously noted, traditional programs based on the transmission of information have no effect on substance use, providing information on substances and their effects is a necessary preliminary step to prevent drug use. For this reason, effective programs usually include an information module on the characteristics of substances (e. Similarly, when providing information, it is necessary to take into account that the information must be objective (i. Social skills training Social skills are probably one of the most important components of school- based programs. Social skills are the set of behaviors manifested by an individual in an interpersonal context that facilitate the establishment of relationships that are appropriate and in keeping with a given situation. The lack of these skills can contribute to the initiation and maintenance of drug use, since it can function as an alternative to achieving emotional and affiliation objectives (Pons and Berjano, 1999), by increasing the sense of confidence to properly deal with others. Resistance skills training assumes that adolescents are persuaded to use drugs by their peers, the media, etc. Therefore, this training tries to teach adolescents to identify the influences, pressures or offers they may receive to use drugs and to deal with them by resisting. For its part, assertiveness is defined as the ability to openly express our rights and opinions while respecting the rights of others. The real intention of this training is that adolescents learn to recognize the difficulties to behaving assertively that may arise and, therefore, to behave assertively in all situations. The excessive importance given to resistance skills training has been recently criticized for not taking into account that in most cases pressure occurs within a group of equals actively selected by the adolescent on an affinity basis. Nevertheless, the carrying out of this training, along with the development of other personal competencies and the correction of normative expectations about drug use by their peers, is essential. Training in personal competencies and skills Personal problems and deficits are considered important risk factors, since the adolescent can turn to drug use in an attempt to compensate for them. Thus, stress and the lack of personal competencies or coping skills are important factors that promote drug use. Therefore, along with training in social skills is included training in other more general skills that strengthen individual resources to deal with any aspect of daily life. Some of the specific components included are: training in problem solving and decision making, setting goals and objectives, coping skills, emotional self- control (managing mood, anxiety and anger), self-reinforcement, public commitment regarding future drug use (non-use or responsible consumption), affective education (self-concept and self-esteem) and the promotion of alternative leisure activities to drug use. Again, note that the methodology used is based on active learning strategies and interactive teaching techniques that facilitate the acquisition of such skills. As we have previously seen, many school-based programs are enhanced by the inclusion of interventions in the family, the community, the media and the school system in a broad sense. In reference to the school climate or context, it is important to stress that the particular normative setting of schools plays a vital role since the probability that a given behavior (e. Therefore, it is essential to establish a "drug policy" that clearly defines rules and procedures about the consumption, availability and distribution of both legal and illegal drugs at the school and its surroundings. Similarly, the measures to take in the event of a breach of the prohibition against the use of tobacco, alcohol or other drugs by any member of the educational community should be clearly established. In this sense, a clear school policy on drug use, especially tobacco and alcohol, facilitates the active involvement of teachers, fostering among them a role of exemplar in relation to the use of drugs. In the same way, it is imperative that the implementation of a program be facilitated, not only by the support of the school but also by the settings closest to the students.

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In order to analyze the mechanisms involved in bacilli intracellular survival buy nizagara online from canada, myco- bacterial gene expression was determined in M purchase nizagara mastercard. Macrophages have been investigated at different time points post-infection for the differential expression of various two-component system regulators (regX3 cheap generic nizagara canada, phoP quality nizagara 100 mg, prrA, mprA kdpE, tcr, devR and tcrX) (Haydel 2004). In this work, the authors reported that ap- proximately one-third (32 %) of the genes upregulated by M. Interestingly, the authors observed high induc- tion of the sigma factor sigG and 13 other putative transcriptional regulators. Therefore, while significant work has been per- 134 Genomics and Proteomics formed on the gene expression profile of the host, information on M. So far, there is only one publication concerning global mycobacterial transcription expression in the animal model, using microarray as the analytical method (Talaat 2004). The same genes were also found to be induced 24 hours post-infection in murine bone marrow macrophages (Schnappinger 2003). Additionally, several genes were regulated up or down only in Balb/c mice, such as proZ (transport system permease protein), aceAa (probable isocitrate lyase involved in lipid metabolism), and genes encoding for regulatory proteins, such as sigK, sigE and kdpE. A gene required for extrapulmonary dissemination (hbhA) was also upregulated in the lung but not in the spleen during the early stages of infec- tion (Delogu 2006). Al- though some differences were observed when comparing human and murine lung, the authors admitted that it was difficult to ascertain whether the infection stage in the analyzed human lung specimens could be correlated with the persistent infec- tion in mice. Proteomics, the global study of proteins that are translated in a given physiological state is one of the most important and ambi- tious goals in M. The proteome of an organism implies not only an inventory of its gene products but also the transduction rate and the post- transcriptional events that occur in the organism (Betts 2002). For a good review on the different techniques used in protein mapping, readers are re- ferred to Patterson et al (2000). For instance, the use of one dimension electrophoresis has been shown to be very useful for the separation of hydrophobic proteins (Simpson 2000). In this, mixtures of pro- teins from bacteria in two different conditions are covalently labeled with isotopi- cally labeled heavy or light forms of the reagents. This new tech- nology has proven to be very useful in the quantitation of complex mixtures of proteins. The study also showed a reduced rep- ertoire of proteins devoted to transport, which might reflect the intracellular life- style. The global analysis of compartmentalized proteins will shed light on host-pathogen interactions, metabolic pathways and cell commu- nication, just to mention some of the mechanisms related to pathogenesis. In addi- tion, many pathogenic bacteria secrete proteins that are involved in virulence (Fin- lay 1997) and thus culture filtrates of M. Cell wall proteins play a fundamental role in cell archi- tecture, resistance of the pathogen to chemical injury and dehydratation, and many other key functions of this microorganism. Thus, the identification of proteins lo- calized in this subcellular fraction may lead, in the near future, to the development of new diagnostic tests and drugs. Membrane proteins demand special attention, because they are involved in host-pathogen interactions, nutrient transport, quorum sensing mechanisms, etc. Even though we are still far from identifying the almost 4,000 genes predicted by genomics, the number of identified proteins increases each year and shows how genomic and proteomic technologies complement each other. In order to map less abun- dant proteins, different methods were applied for their separation, which allowed the identification of 12 novel proteins, five of them with a known function (Ro- senkrands 2000b). The study also showed the identification of a protein that was not predicted by genomics and revealed the presence of alternative start codons. Six proteins were identified, all of them with molecular masses between 13,200 and 7,200 kDa and with isoelectric point (pI) ranges between 4. But in particular, the technique is biased towards the preferential identification of the most abundant proteins. Therefore, less abundant proteins, such as transcriptional regulators, are rarely detected when whole cell lysates are analyzed (Gygi 1999). Each one of these techniques has been shown to be adequate for the identification of certain classes of proteins. Proteins of high mo- lecular mass, such as the 230,621 Da polyketide synthase ppsC, were also identi- fied. A total of 705 proteins were identified in the membrane, 306 were localized in the cell wall, and 356 in the cytosol fraction. The study also included a computational analysis of protein net- works, one of the most exciting fields in the coming years. In order to overcome these problems, fractions of cellular membranes were prepared by differential centrifu- gation and separated by one-dimensional electrophoresis. Very hydrophobic proteins, including those with 15 transmembrane helices, were detected in this study. The use of alternative solubilizing agents, such as Tri- ton X-114, has proven to be a good choice for membrane fractionation. The deter- gent was shown to be useful in the identification of nine novel proteins that have been already incorporated in the M. Some of the 18 proteins were over- expressed in one or the other strain, and some shifted their mobility probably due to the presence of amino acid substitutions. The studies on comparative proteomics allowed the identification of isopropyl malate synthase exclusively in the M. Similarly, a spot corresponding to the HisA pro- tein, which is involved in the histidine biosynthetic pathway, was detected in the M. Another interesting feature in the same study was the mobility variations of the transcriptional regulator MoxR, which the authors attributed either to amino acid changes or to post-translational modifications. Transcriptional regulation differences between strains might be the key to under- standing how virulence factors are involved in a variety of roles, including host-cell invasion, survival within the host cell, and long-term persistence. In contrast, the proteomic profile of an organism in a particular physiological situation complements and helps to decipher its inter- action with the environment. Inside the granuloma, it faces low oxygen tension, starvation, low pH, reactive nitrogen, and reactive oxygen species, among other offenses (Schnappinger, 2006). The bacillus has developed adaptive mechanisms for survival and persistence in these hostile environments. The mechanisms governing this state are still not fully understood and the protein expression profile in models mimicking the dormant state is an issue of intense research. Different in vitro models have been developed, aimed at simulating the in vivo conditions in- ducing dormancy (Wayne 1996, Betts 2002, Voskuil 2003). Hypoxia is among the most conspicuous conditions encountered by the tubercle bacilli in the central part of the granuloma, where bacilli are considered to remain dormant. The comparison of the protein content between aerobic and anaerobic cultures identified up to seven proteins that were more abundant in hy- poxic conditions. The main proteins characterized were fructose biphosphate aldol- ase (in culture filtrate only), hypothetical protein Rv0569, and alpha-crystallin pro- tein, also known as HspX. Other proteins identified included hypothetical proteins Rv2623 and Rv2626c, L-alanine dehydrogenase (only in culture filtrates), and BfrB, a bacterioferritin involved in iron uptake and storage. Among the hypothetical proteins found were Rv2005c, with similarity to universal stress proteins, Rv0560c, Rv2185c, and Rv3866. In spite of the enormous advances in biochemical ana- lytical techniques, the purification and identification of proteins is not always an easy task. Proteomic studies seem to be a successful way to discover new virulence factors, drug target molecules and proteins involved in pathogenic mechanisms. Metabolomics state-of-the-art The term metabolomics was first coined in 1998 (Oliver 1998) to describe the “change in the relative concentrations of metabolites as the result of deletion or over-expression of a gene”. At the same time, the term metabolome analysis re- ferred to the analysis of metabolites in the phenotypic profile of E. Later on, metabolomics was considered the detection and measurement, under defined conditions, of cellular metabolites such as low molecular weight molecules present in an organism or biological sample. Metabolites are in gen- eral defined as those small molecules, usually intermediate and final products of metabolism, but the definition also applies to high molecular weight molecules such as lipids, peptides and carbohydrates (sometimes referred to as “lipidomics”, etc). Metabolomic approaches are now feasible due to the rapid improvements that have taken place during the last decade in two areas: analytical chemistry and bioinfor- matics. In the latter case, all the conditions required for an accurate quantification should be considered, such as the use of appropriate data standards, etc (Nielsen 2005). Metabolomics can also help to validate in silico pathways prepared on the basis of available genome sequences and established databases (Park 2005). Metabolomic analysis has mainly been used in studies on plants and human pathol- ogy; in this latter case, the attention was focused on searching for metabolites asso- ciated with disease, in other words, “metabolites as biomarkers of disease” (Weckwerth 2005). Microbial metabolomics has initially been devoted to explore bacterial or fungal strains carrying improved phenotypes with a certain biotechnol- ogy usefulness value (Wang 2006).

The sigmoid colon empties into the rectum buy discount nizagara 25 mg on-line, which serves as a temporary storage area for indigestible or unabsorbable food residue (see Figure 11-3) generic nizagara 100 mg online. At intervals purchase 50mg nizagara fast delivery, usually after meals purchase cheapest nizagara and nizagara, the involuntary muscles within the walls of the large intestine propel solid waste material, called feces or stool, toward the rectum. This material is then eliminated from the body by both voluntary an involuntary muscle actions, a process called defecation. As mentioned systemic antibiotic therapy may destroy these bacteria and others living In the large intestine, causing undesirable side effects. The Accessory Structures The Liver The liver, often referred to by the word root hepat, is the largest glandular organ of the body (Figure 11-7). It has a large right lobe and a smaller left lobe; the right lobe includes two inferior smaller lobes. The hepatic artery carries oxygenated blood, whereas the portal system of veins carries blood that is rich in the end products of digestion. This most remarkable organ has so many functions that only some of its major activities can list here: 1. When the blood sugar level 326 Human Anatomy and Physiology falls below normal, liver cells convert glycogen to glucose and release it into the bloodstream; this serves to restore the normal concentration of blood sugar. The detoxification (removal of the poisonous properties) of harmful substances such as alcohol and certain drugs 8. The storage of some vitamins and iron The main digestive function of the liver is the production of bile. The salts contained in bile act like a detergent to emulsify fat, that is, to break up fat into small droplets that can be acted on more effectively by digestive enzymes. After collecting bile from the gallbladder, this 327 Human Anatomy and Physiology duct, now called common bile duct, delivers bile into the duodenum. The Gallbladder The gallbladder is a muscular sac on the inferior surface of the liver that serves as a storage pouch for bile. Although the liver may manufacture bile continuously, the body is likely to need it only a few times a day. Consequently, bile from the liver flows into the hepatic ducts and then up through the cystic duct connected with the gallbladder. When chyme enters the duodenum, the gallbladder contracts, squeezing bile through the cystic duct and into the common bile duct leading to the duodenum. The protein digesting enzymes are produced in inactive forms, which must be converted to active forms in the small intestine by other enzymes. The pancreas also produces large amounts of alkaline fluid, which neutralizes the chyme in the small intestine, thus protecting the lining of the digestive tract. These juices collect in a main duct that joins the common bile duct or empties into the duodenum near the common bile 328 Human Anatomy and Physiology duct. Also, in some cases of gallbladder disease, disease, infection may extend to the pancreas and cause abnormal activation of the pancreatic enzymes. In either circumstance, the pancreas suffers destruction by its own juice, and the outcome can be fatal; this condition is known as acute pancreatitis. The pancreas also functions as an endocrine gland, producing the hormones insulin and glucagons that regulate sugar metabolism. Digestion and Absorption of Carbohydrates, Fats, and Proteins Digestion Digestion, a complex process that occurs in the alimentary canal, consists of physical and chemical changes that prepare food for absorption. Mechanical digestion breaks food into tiny particles, mixes them with digestive juices, moves them 329 Human Anatomy and Physiology along the alimentary canal, and finally eliminates the digestive wastes from the body. Chewing or mastication, swallowing or deglutition, peristalsis, and defecation are the main processes of mechanical digestion. Chemical digestion breaks down large, nonabsorbable food molecules−molecules that are able to pass through the intestinal mucosa into blood and lymph. Chemical digestion consists of numerous chemical reactions catalyzed by enzymes in saliva, gastric juice, pancreatic juice, and intestinal juice. Carbohydrate Digestion Very little digestion of carbohydrates (starches and sugars) occurs before food reaches the small intestine. Salivary amylase usually has little time to do its work because so many of us swallow our food so fast. But after the food reaches the small intestine, pancreatic and intestinal juice enzymes digest the starches and sugars. A pancreatic enzyme (amylase) starts the process by changing starches into a double sugar, namely, maltose. Three intestinal enzymes−rnaltase, sucrase, and lactase−digest double sugars by changing them into simple sugars, chiefly glucose (dextrose). Maltase digests maltose (malt sugar), sucrase digests sucrose (ordinary cane sugar), and lactase digests lactose (milk sugar). The end product of carbohydrate 330 Human Anatomy and Physiology digestion is the so-called simple sugar; the most abundant is glucose. Two enzymes (renin and pepsin) in the gastric juice cause the giant protein molecules to break up into somewhat simpler compounds. Pepsinogen, a component of gastric juice, is converted into active pepsin enzyme by hydrochloric acid (also in gastric juice). In the intestine, other enzymes (trypsin in the pancreatic juice and peptidases in the intestinal juice) finish the job of protein digestion. When enzymes have split up the large protein molecule into its separate amino acids, protein digestion is completed. Fat Digestion Very little carbohydrate and fat digestion occurs before food reaches the small intestine. Most fats are undigested until after emulsification by bile in the duodenum (that is, fat droplets are broken into very small droplets). After this takes place, pancreatic lipase splits up the fat molecules into fatty acids and glycerol (glycerine). For example, the name amylase indicates that the enzyme digests carbohydrates (starches and sugars), protease indicates a protein- digesting enzyme, and lipase means a fat-digesting enzyme. When carbohydrate digestion has been completed, starches (polysaccharides) and double sugars (disaccharides) have been changed mainly to glucose, a simple sugar (monosaccharide). Absorption After food is digested, it is absorbed; that is, it moves through the mucous membrane lining of the small intestine into the blood and lymph. In other words, food absorption is the process by which molecules of amino acids, glucose, fatty acids, and glycerol goes from the inside of the intestines into the circulating fluids of the body. As long as food stays in the intestines, it cannot nourish the millions of cells that compose all other parts of the body. Their lives depend on the absorption of digested food and its transportation to them by the circulating blood. Table 11-1 Chemical Digestion Digestive juices and Substance Digested Resulting Products* enzymes (or hydrolysed) Saliva Starch (Polysaccharide) Maltose (disaccharide) Amylase Gastric Juice Proteins Partially digested Protease (Pepsin) proteins plus hydrochloric acid Pancreatic Juice Proteins (intact of Peptides Protease (trypsin) and partially digested) Fatty acids, amino Lipase Fats emulsified by bile acids and glycerol Amylase Starch Maltose Intestinal Juice Amino acids Peptidases Peptides Glucose and fructose Sucrase Sucrose (cane sugar) (simple sugars) Lactase Lactase (Milk sugar) Glucose and galactose Maltase Maltase (malt sugar) (Simple sugars Glucose *Substances underlined are end products of digestion (that is, completely digested foods ready for absorption) 333 Human Anatomy and Physiology Review Questions 1. If you inserted 9 inches of an enema tube through the anus, the tip of the tube would probably be in what structure? The urinary system consists of: - Two kidneys: this organ extracts wastes from the blood, balance body fluids and form urine. They 338 Human Anatomy and Physiology are protected at least partially by the last pair of ribs and capped by the adrenal gland. On the medial concave border is the hilus (small indented area) where blood vessels, nerves & ureters enter and leave the kidney. Covering and supporting each kidney are three layers of tissue: • Renal capsule – innermost, tough, fibrous layer • Adipose capsule – the middle layer composed of fat, giving the kidney protective cushion. The renal pelvis is the large collecting space with in the kidney formed from the expanded upper portion of the ureters. Filters (by hydrostatic presure) water, dissolved substances (minus most plasma proteins, blood cells) from blood plasma. The major functions of the kidneys are: 343 Human Anatomy and Physiology All the functions are directly or indirectly related to the formation of urine. The series of events leads to: - To the elimination of wastes - Regulation of total body water balance.

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The cholesterol concentration of blood in human is between 150 to 250 mg per 100 ml order nizagara 100 mg, being distributed equally between the cells and the plasma buy genuine nizagara on line. Formation of acetyl CoA A molecule of acetic acid combines with coenzyme A (CoA) to produce Acetyl CoA in the presence of an enzyme Acetyl CoA synthetase nizagara 25 mg generic. Formation of acetoacetyl CoA Two molecules of acetyl-CoA condense to form an acetoacetyl-CoA molecule buy nizagara 50 mg mastercard, catalyzed by the enzyme “thiolase”. Squalene, with the formation of various intermediates fnally give rise to the end product cholesterol. Primary bile acids include cholic acid and chenodeoxy cholic acid and secondary bile acids include deoxycholic acid and lithocholic acid. Importance Bile acids are C steroids, detergent like compounds that are responsible for 24 the emulsifcation and absorption of lipids in the intestine. Bile salts Cholic acid is conjugated in the liver with either glycine or taurine through peptide linkages forming the bile salts glycocholic acid and taurocholic acid respectively. They combine with sodium and potassium present in the bile and form water soluble alkaline bile salts, namely sodium glycocholate and sodium taurocholate respectively. Importance Vitamin D is a derivative of cholesterol and the precursor of para thyroid hormone which regulates calcium and phosphate metabolism in vertebrates. They are present both in cytoplasm as well as in the cell membranes and serve important functions in both cell activity and cell permeability. Phospholipids are made up of fatty acids, nitrogenous base, phosphoric acid and glycerol or other alcohol. Sphingolipids In this group of substances, glycerol is replaced by a complex amino alcohol “Sphingosine”. In all tissues except liver, phospholipids are synthesized, utilised and degraded in situ; while in liver large proportion of the phospholipids after synthesis is transferred to the plasma and as a matter of fact, liver is practically the sole source of plasma phospholipids. The choline component of lecithins is derived by the stepwise methylation of ethanolamine which in turn is formed by the decarboxylation of serine. When lecithin is acted upon by the enzyme phospholipase A it is converted into lysolecithin and a free fatty acid. This enzyme transfers the fatty acid moiety from the lecithin to the cholesterol to form cholesterol ester. A lecithinase in cobra venom readily split off an unsaturated fatty acid in lecithin producing “lysolecithin”. Lecithinase from snake venom hydrolyses cephalins to lysocephalins which are similar to the formation of lysolecithin from lecithin. Atherosclerosis is manifested by deposition of cholesterol and other lipids on the inner walls of blood vessels. This leads to occlusion of blood vessels in the heart and the brain, resulting in increased blood pressure, strokes and heart attacks. The causative factors for atherosclerosis include, smoking, obesity, lack of physical exercise, emotional stress and high fat diet. Though many hypolipidemic drugs are commercially available to control the cholesterol levels, they often elicit harmful side effects. Nucleic acids are present both in the free state as well as conjucated with proteins (Nucleoproteins). Deoxyribonucleic acid Structural Components of Nucleic acids Components Ribonucleic acid Deoxyribonucleic acid Acid Phosphoric acid Phosphoric acid Pentose Sugar D-ribose D-2 deoxy ribose Nitrogen Bases i. It contains 3 monovalent 3 4 hydroxyl groups and a divalent oxygen atom, all linked to a pentavalent phosphorus atom. One possesses D-2-deoxyribose, (deoxyribonucleic acid) while the other contains D-ribose (hence called ribonucleic 89 acid). Purine Bases These are all derived from their parent compound purine, which contains a six membered pyrimidine ring fused to the 5 membered imidazole ring, the purine derivatives found in nucleic acids are adenine and guanine. They are 5 methylcytosine, N4 acetyl cytosine, N6 methyladenine, N6, N6 dimethyladenine and pseudouracil etc. This enzyme catalyses the polymerization of mononucleotides to 91 polynucleotides, which needs the following for its action. A template strand dictates the synthesis of the new daughter strand and sequence of the template strand determines the addition of the nucleotides. The results show that they form bands with intermediate density alone in the frst generation, which confrms the semiconservative model of replication. Exonucleases are the nucleases that attack only the internucleotide bonds located at the ends of the nucleic acid. Endonucleases are the nucleases that attack only the internucleotide bonds located throughout the length of the nucleic acid chain (in the middle). Nucleotidases (Phosphatases) These enzymes hydrolyse the nucleotides to the corresponding nucleosides and inorganic phosphate molecules. Phosphatase Nucleotides Nucleoside + Phosphate Nucleosidases (Nucleoside phosphorylase) The nucleosides obtained above either absorbed or degraded into bases and sugars by nucleosidases. Mechanism Transcription involves 3 stages i) Initiation ii) Elongation iii) Termination Three phases of transcription 1. This complex enzyme, called the holoenzyme is needed to initiate transcription since the s factor is essential for recognition of the promoter. It is common for prokaryotes to have several s factors that recognize different types of promoter (in E. The holoenzyme binds to a promoter region about 40-60 bp in size and then initiates transcription a short distance downstream (i. With in the promoter lie two 6 bp sequences that are particularly important for promoter function and which are therefore highly conserved between species. Using the convention of calling the frst nucleotide of a transcribed sequence as +1, there 2 promoter elements 98 lie at position -10 and -35, that is about 10 and 35 bp respectively, downstream of where transcription will begin. The most common termination signal is a G ≡ C rich region is a palindrome, followed by an A = T rich sequence. Those that lack such a structure require an additional protein, called rho protein (r) to help recognize the termination site and stop transcription. The product of transcription in eukarryotes are called as primary transcripts and they undergo modifcation by a process called post transcriptional modifcation. Okasaki fragments are present in i) both the parental strands ii) both the daughter strands iii) leading strand iv) lagging strand c. G-C rich region followed by A-T rich region is a signal for i) initiation ii) elongation iii) termination iv) primer formation d. One among the following is not a modifed base i) pseudo uridine ii) isopentyl adenine iii) methyl guanosine iv) deoxy thymine e. The metabolism of our body comprises two major balanced activities: anabolism (synthesis) and catabolism (degradation). Whether the metabolic changes are exergonic or endergonic, most of them have to be catalysed by enzymes. If one particular enzyme is defcient or absent then that leads to a block in the pathway of biochemical reactions leading to metabolic abnormalities which are present throughout the life and handed over to the progeny. The absence or defciency of an enzyme will cause an abnormal accumulation of the intermediate products of metabolism in the body and increased excretion in urine as such or their degradation products. For example, in the following reaction a c b d R B C D P R is the reactant, B, C and D are intermediates and P is the product and a, b, c and d are enzymes catalyzing various steps of the reactions. In this reaction pathway, if any one of the enzyme is defcient or absent, the previous intermediate accumulates and produces toxicity. It also affects the amount of product (P) formation which may be essential biologically and there by leads to pathological diseases. Beadle and Tatum put forth their theory of one gene one enzyme hypothesis which states that one gene controls the synthesis of a single enzyme. Galactosemia, Von-Gierke’s disease, hemophilia, albinism, alkaptonuria and Tay-Sach’s disease are some of the important diseases due to inborn errors of metabolism. Due to the enzyme defect galactose accumulates in blood and is reduced by aldose reductase in the eye to the corresponding galactitol which causes cataract. The general condition is more severe if it is due to a defect in galactose 1 - phosphate uridyl tranferase, since galactose 1- phosphate accumulates and depletes the liver of inorganic phosphate. After 2 - 3 months of age the liver may show fatty infltration and lead to cirrhosis (non functioning of liver cells). Galactosemia at this age is associated with mental retardation due to accumulation of galactose and galactose 1 - phosphate in cerebral cortex.

Ross discusses this reaction and the difficulty in handling it for those close to the person by explaining that we should put ourselves in the client’s position and consider how we might feel intense anger at having our life interrupted abruptly buy nizagara 100mg cheap. The person attempts to strike a bargain for more time to live or more time to be without pain in return for doing something for God purchase nizagara 100 mg overnight delivery. Usually order nizagara overnight, when people have completed the processes of denial buy cheap nizagara, anger, and bargaining, they 341 move into depression. In this form of depression, the person is reacting against the impending loss of life and grieves for him or herself. This occurs when the person has worked through the previous stages and accepts his or her own inevitable death. With full acceptance of impending death comes the preparation for it; however, even with acceptance, hope is still present and needs to be supported realistically. Personal values and beliefs about life; views of personal successes, both financial and emotional; the way they look physically when experiencing the dying process; their family and friends and their families’ attitudes and reactions; their past experiences in coping with difficult or traumatic situations; and, finally, the health care staff who are caring for them during this process – all affect an individual’s attitude toward dying. Notify the charge nurse if there is an impending crisis and perform emergency actions until help arrives. Encourage dying clients to do as much as they can for themselves so that they do not just give up-a state that only reinforces low self-esteem. Recognize that your physical presence is comforting by staying physically close to the client if he or she is frightened. Respect the client’s need for privacy and with draw if the client has a need to be alone or to disengage from personal relationships. Be tuned into client’s cues that he or she wants to talk and express feelings, cry, or even intellectually discuss the dying process. Understand that different family members react differently to the impending death and support the different reactions. Be aware that demonstrating your concern and caring assists the family to cope with the grief process. Explore your own feelings about death and dying with the understanding that until you have faced the subject of death you will be inadequate to support the client or the family as they experience the dying process. Share your feelings about dying with the staff and others; actively work through them so that negativity does not get transferred to the client. To show kindness to the family Equipment • Basin for water, wash cloth and towel • Cotton • Gauze • Dressings and tape if necessary • Clean sheet • Stretcher • Forceps • Name tag • Gloves, if necessary Procedure • Note the exact time of death and chart it • If the doctor is present call him to pronounce death • If the family members are not present, send for them 347 • Wash hands and wear clean gloves according to agency policy • Close doors of the room or pull curtain • Raise bed to comfortable working level (when necessary) • Arrange for privacy and prevent other patients from seeing in to room. Airborne precaution precaution taken when a person has an illness that can be carried in the air or in the dust particles. Apex lower point of the heart, formed by the tip of the left ventricle Apical pulse pulse normally heard at the heart’s apex, which usually give the most accurate assessment of pulse rate Aspiration Inhalation of foodstuff, vomitus or saliva into the lungs. Asphyxia A condition produced by prolonged lack of oxygen 350 Asepsis Absolute freedom from all microorganisms Antiseptic Harmless chemicals that can kill microorganisms or prevent them from multiplying. Blood pressure The force exerted by the heart to pump the blood around the body Bradycardia Abnormally slow heartbeat. Brand name copyright name assigned by a company that makes the medication; also called the trade name. Brain death irreversible cessation of brain and brain stem function to the extent that 351 cardiopulmonary function must be mechanical maintained. Capsule a small gelatinous case for holding a dose of medicine; a membranous structuring enclosing another body structure, as the articular capsule in a joint. Center of gravity the center of one’s weight; half of one’s body weight is below and half above, and half to the left and half to the right of the center of gravity. Cheyne-Stkes respiration: breathing characterized by deep breathing alternating with very slow breathing or apnea often precedes death. Contact precaution precaution taken against disease that can be transmitted through direct contact between a susceptible host’s body surface and an infected or colonized person. Dangling positioning of a client so that he or she is sitting on the edge of the bed with legs down and feet supported by a footstool or the floor. Debridement removal of foreign, dead, and contaminated material from a wound, so as to expose healthy underlying tissue. Diagnosis The decision regarding the nature of an illness, arrived at by clinical assessment of the patient and result of investigation. Dorsal lithotomy examination position in which the client is lying on his or her back with the feet in stirrups. Droplet precaution precautions taken to prevent the spread of diseases transmitted by microorganisms propelled through the air from an infected person and deposed on the host’s eyes, nose or mouth. Elective (surgery) case in which the client’s condition is not life threatening and may choose whether or not to have surgery; also called optional surgery. Embolus a foreign substance, blood clot, fat globule, piece of tissue, or air bubble carried in a blood Enema An injection of fluid into the colon or rectum. Eupnea normal respiration Eviceration the protrusion of the intestines through an abdominal wound ; removal of the internal body contents. Exudate material that escapes from blood vessels and is deposited in tissue or on tissue surfaces; usually contains protein substances. Fahrenheit System of measuring heat Femoral pulse pulse felt in the groin over the femoral artery Fecal impaction accumulation of hardened stool in the rectum. Footdrop contructure deformity that prevents the client from putting the heel on the floor; results from improper positioning or anterior leg muscle paralysis. Gastrostomy Making an artificial opening into the stomach through which the patient is fed by pouring nourishment through a tube directly into the stomach. Kusmal’s breathing sever paroxysmal dyspnea, as in diabetic acidocis and coma Laceration a wound produced by tearing or ripping (as opposed to an incision made in surgery). Line of gravity direction of gravitation pull; an imaginary vertical line through the top of the head, center of gravity, and base of support. Medication substance other than food used to prevent disease, to aid in diagnosis and treatment and to restor or maintain functions in the body tissues; also called drug. Occupied bed bed holding a client that is unable to get up as a result of his or her condition or generalized weakness. Oral of or pertaining to the mouth Orthopenia difficult breathing relieved by seating or standing erect Output All fluid lost from the body. Parenteral administered in to the body in a way other than through the alimentary canal (subcutaneous, intravenous, intramuscular), as parenteral medication Pedal pulse pulse on the foot felt over the dorsal pedis artery or posterior tibial artery Perineal care bathing the genital and surrounding area. Perioperative the period surrounding surgery; includes preoperative, intraoperative, and postoperative periods. Pharmachokinetics actions of drug Pharmachology the study of chemicals (drugs, medications) and their effect. Potentiation enhancement of one agent by another, so that the combined action is greater than the sum of the two. Postural drainage Position adapted to facilitate expectoration of material in patients with lung disease. Pressure ulcer ulcerated sore often cause by prolonged pressure on a bony prominence or other area, especially if the client is allowed to lie in one position for an extended period. Protective device piece of equipment, most often a vest or a belt, used to ensure the safety of the client ()ie, helping client to remain in a chair without falling); also called a client reminder device. Protective isolation attempts to prevent harmful microorganisms from coming into contact with the client; also called reverse or neutropenic isolation Pulse The beat of the heart felt in the arteries. Recumbent lying down Rotation process of turining about an axis, as rotation of the hand of the fetus in preparation of delivery. Rectal of the rectum Retention enema An injection of fluid that is retained in the rectum for absorption into the blood stream. Splint A device for immobilizing part of the body Spore The seeds of microorganisms, which are resistant to drying, heat, and disinfectants Standard precaution precautions designed for the care of all clients regardless of diagnosis or infection status. Sterile Specially treated so that all microorganisms are destroyed 361 Stethoscope Instrument for magnifying sound Specimen A small amount of body excretion or body fluid that is sent to a laboratory for examination. Suppository Rectally administered cones containing a medication in the base that is soluble at body temperature. Systole Blood pressure period during the beating phase of the heartbeat during which blood is expelled from heat. Synergism joint action of agents in which the combined effects is greater than the sum of the individual parts. Tachypenea conditions in which breaths are abnormally rapid, more than 20 per minute Thermometer An instrument used to measure temperature. Traction exertion of a pulling force ; an apparatus attached to the client to maintain stability of 362 a joint or aligned fracture or to exert a pulling force elsewhere, as in the lower back, to relieve pressure. Transimission-based- precaution: precaution designed for clients with specific infection or diagnoses Tympanic membrane eardrum.

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A recent systematic review and meta-analysis has shown that specificity does not vary sub- stantially between different methods purchase nizagara once a day, but sensitivity can be improved cheap 25mg nizagara mastercard. By compari- son with direct smears purchase 100mg nizagara with mastercard, centrifugation and overnight sedimentation are more sensi- tive when preceded by any of several chemical methods cheap nizagara online amex, including the bleach method (Steingart 2006a). No other major improvement has been obtained in the classical staining method based on the Ziehl-Neelsen technique developed many years ago. Fluorescent microscopy proved to be faster and more sensitive than conventional microscopy based on Ziehl-Neelsen staining, and is the standard diagnostic method in high-income countries (Steingart 2006b). It has the additional advantage of de- manding less effort from the laboratorist, thus reducing fatigue and human error. As for low-income countries, the eventual introduction of fluorescent microscopy should be evaluated carefully because it requires a more expensive microscope and a more complex technique. It should be noted, however, that the main burden of fluorescent microscopy lies in the maintenance of the mercury lamp, rather than in the initial cost of the equipment. Lately, an inexpensive device has been released onto the market that can be adapted to any fluorescence microscope. This form of illumination is suitable for the de- tection of auramine O-stained bacilli and may become an affordable alternative for improving diagnostic microscopy in laboratories serving poor-income settings with a high load of smear examinations (Van Hung 2007). Fluorescein diacetate staining was recently evaluated for assessing bacilli viability in sputum smears. Although slow and time-consuming, it is relatively simple to perform and rather inexpensive in most settings. It is now standard recommendation that the combination of a solid and a liquid culture medium gives the best sensitivity in recovering mycobacteria in primary culture (Tenover 1993). Com- pared to culture and clinical status, nucleic-acid amplification tests have high sen- sitivity and specificity in smear-positive samples. However, lower values are ob- tained in smear-negative specimens, precluding their use as a screen to rule out the disease. The current recommendation is that molecular tests should always be in- terpreted in conjunction with the patient’s clinical data (Pfyffer 2003). More evaluations in target populations are needed to assess the real impact on the diagnosis of the disease (Espy 2006, Savelkoul 2006). Additionally, it has various disadvan- tages, such as variability in the interpretation by different readers, the need of some experience to correctly interpret the result, and the requirement for the patient to return after 48-72 hours for test reading. Further studies comparing these two assays are needed, especially in immunosuppressed patients (Richeldi 2006). There is an urgent demand for a field-friendly test, ideally, a point-of-care one able to diagnose the disease on the spot in order to avoid delays in diagnosis, thus, preventing further transmission and reducing com- plications. This type of test is particularly useful when patients do not return for care and would greatly benefit people in settings such as prisons, homeless shelters, and clinics for migrant workers who have no ready access to, or do not seek, public health service assistance. Serological tests - aimed at the detection of either antigens specific to, or antibodies directed against M. In particular, in the development of tests for antibody detection, careful attention should be paid to the selection of the target group and the control population groups for performance evaluation. Inclusion and exclusion criteria should be quite stringent regarding age range, geo- graphical location, previous exposure to M. Unfortunately, some serological tests are being marketed in developing countries without a proper on-site assessment. In order to improve performance, a comprehensive set of purified, well-characterized antigens should be investigated, searching for differ- ences in patterns of response rather than comparing responses to individual candi- date antigens. A quite different approach that utterly fulfills the requirements of the point-of-care diagnosis is based on the electronic nose technology, which is able to detect and identify tiny amounts of virtually every substance in a few minutes. The device can be assembled as the sensory part of a portable artificial intelligence system, able to detect several microbes simultaneously through their specific “odors. This methodology, although simple to perform and rather inexpensive, is quite slow and laborious, requiring several weeks to give the final results (Heifets 1999). Many alternative approaches and methods have been proposed, some of which have already been presented in Chapter 19 (Palomino 2007, Piersimoni 2006). The most important consideration before they can be implemented in the routine diagnostic laboratory is that they are better and faster than the currently available methods and that they have been properly evaluated and have shown high accuracy in target populations. Several molecular tools have also been developed and proposed as rapid methods to detect drug resistance (Garcia de Viedma 2003). Molecular methods have sev- eral advantages over culture-based techniques: shorter turnaround time, no need for growth of the organism, the possibility for direct application in clinical samples, less biohazard risks, and feasibility for automation. In most cases, molecular methods have been directed towards detecting resistance to rifampicin for two major reasons. First, rifampicin resistance is a good surrogate marker for treatment failure and, in settings with a high prevalence of drug resistance, for multidrug resistance. Second, the associated mutations are well defined, restricted to a short chromosomal seg- ment, and their prevalence is sufficiently known worldwide (see Chapter 19). The desideratum would be to achieve identification and multiple drug resistance detection directly on clinical specimens, thus avoiding the delay implied in culturing the bacilli (Cavusoglu 2006, Kim 2006, Marin 2004, Park 2006, Sekiguchi 2007, Somoskovi 2006, Yang 2005). On drug development Associated with the problem of drug resistance is the search for new anti- tuberculosis drugs. As mentioned in previous chapters of the book, almost no new anti-tuberculosis drug classes have been developed over the last 40 years. Many candidate compounds have been considered in the last decade, but very few of them have entered into further evaluations. These po- tentially useful anti-tuberculosis drugs are currently in different stages of the evaluation pipeline. The program aims at using this fluoroquinolone instead of ethambutol or isoniazid in the first-line drug scheme of anti-tuberculosis treatment, in order to shorten the current 6-month duration of the treatment (Burman 2006). A similar program is being carried out in Africa, where gatifloxacin, another fluoroquinolone, is also substituted for ethambutol. On vaccine development 671 The availability of such a spectrum of new drug candidates offers great promise but also entails a great challenge. In the immediate future, a com- plete series of clinical trials will be needed to find the optimal treatment scheme of ultra-short duration, i. Applying a Monte Carlo simulation model, they evaluated drug development from the perspective of a public-private partnership, taking into ac- count several factors such as the expected number of successful compounds, the expected costs of each stage of development and the development costs for suc- cessful and unsuccessful compounds. As for the currently-available candidate drugs in all stages of development, the probability of at least one successful compound being generated was less than 5 %. Obviously, many more efforts and funding are required to reach the objectives of developing new and successful anti-tuberculosis drugs in the near future. Research and development is also needed on innovative drug formulations and drug delivery systems aimed at increasing compliance and achieving a high local drug concentration while minimizing systemic side effects. In this respect, the growing field of inhalation therapy offers a very promising new prospect (Chow 2007, Shoyele 2006). This technology – presented as a simple, low- cost, disposable, dry-powder inhaler – can be applied to the delivery of anti- tuberculosis drugs (Edwards 2006). It is not appealing for the industry, because it demands a huge investment, takes a long time and the risk of failure is high. Besides, even in the best scenario, profit margins are meager and the risk of legal prosecution in the event of side effects is high (Rosenthal 2006). Moreover, major obstacles also lie in the initial vaccine design itself, such as the difficulty in inducing a potent and long-lasting cellular immune response in hu- mans, due to our poor understanding of host-parasite interactions. This hemolytic enzyme, produced by Listeria monocytogenes, allows the agent to escape from the phagosomes of in- fected host cells. This latter finding should be highlighted because the selection of strains used for challenging any vaccine candidate is not a minor issue. Future vaccines must prove able to protect against the most prevalent, transmissible and/or virulent lineages worldwide, not merely against laboratory-domesticated strains (Lopez 2003). The design is based on the fact that viral vectors, such as poxviruses, are powerful at boosting previously primed T-cell responses against intracellular pathogens. Besides, the strategy is feasible and practi- cal in low-resource high-burden countries (McShane 2005). Most importantly, this pioneer study also raises highly sensitive protocol issues and, in particular, ethical issues (Ibanga 2006). They gathered a large body of evidence on the evolutionary sequence of events leading to modern vaccine variants. These mutations might have been responsible for a gradual loss in immunogenicity and protection ability.

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