Papillary lesions must be removed

MANY women who have a breast tumour are told by their doctors that it's OK to leave the lump where it is, that it's unlikely to cause a problem. For many tumours, that's true. But one particular type of breast lump -- called a papillary lesion -- should always be surgically removed, doctors now say. A study in the March issue of Radiology found that papillary lesions can appear normal when biopsied using a needle but can actually be cancerous or precancerous.

Voren Suppositories

Ingredient(s) Voren Suppositories 12.5mg Each supp. contains Diclofenac Sodium 12.5mgVoren Suppositories 25mg Each supp. contains Diclofenac Sodium 25mgVoren Suppositories 50mg Each supp. contains Diclofenac Sodium 50mgPharmacology (Summary of Pharmacodynamic and Pharmacokinetics) 1. Diclofenac is a potent non-steroidal anti-inflammatory (NSAID) with analgesic and antipyretic properties. It also has some uricosuric effect.

Vitbion Forte

DESCRIPTION TABLETColour OrangeShape Round a BiconvexCoating Film-coatedCONTENT Each tablet contain Thiamine HCI 100 mgPyridoxine HCI 200 mgCyanocobalamin 200 gPHARMACODYNAMICS Thiamine is fundamentally associated with carbohydrate metabolism. By combining with the pyrophosphoric acid in nucleated cells, particularly in the liver, kidneys, and white blood cells, it is converted in the body to its pyrophosphate (cocarboxylase) which acts as a coenzyme in such reactions as the decarboxylation of...

Ascorbic Acid Sodium Ascorbate, Vitamin C

Vitamin C is the L-enantiomer of ascorbic acid. Commercial vitamin C is often a mix of ascorbic acid, sodium ascorbate and or other ascorbates. Ascorbic acid is an organic acid and antioxidant also known as vitamin C. Ascorbic acid is easily oxidized and so is used as a reductant in photographic developer solutions (among others) and as a preservative. The L enantiomer of ascorbic acid is also known as vitamin C (the name ascorbic comes from its property of preventing and curing scurvy).

Parenteral Dosage Forms

Most injectable products are solutions. Solutions of drugs suitable for parenteral administration are referred to as injections. Although usually aqueous, they may be mixtures of water with glycols, alcohol, or other nonaqueous solvents. Many injectable solutions are manufactured by dissolving the drug and any excipients, adjusting the pH, sterile filtering the resultant solution through a 0.22-p.m membrane filter, and, when possible, autoclaving the final product.

Quantitative Microscopy

In addition to measuring the size of cells and tissues with the eyepiece or stage micrometers, a number of other quantitative values are utilized for the microscopic evaluation of botanicals (predominantly leaves). These include palisade ratios, vein islet and stomatal numbers, and sto-matal index Palisade ratios. The palisade ratio is the average number of palisade cells that occur beneath an epidermal cell.

Different Sections Different Views

Anatomical characteristics that are used for identification of plant parts are located either on the surface or in the inner tissues of the plant part. If the structures are on the surface, as is typical of delicate leaves and floral structures, and the material is thin enough to allow for light to pass through, no sectioning is required and the sample can be cleared and viewed (see Surface View section). Materials rich in thermolabile compounds that can be destroyed when exposed to heat, such...

Regional distribution of receptors

Radioligand binding on membrane preparations provides information concerning the interaction between drugs and well-defined receptors, as well as about the occurrence of such receptors in certain tissues or organs. However, most tissues and organs are very complex and comprise a number of different cell types, each with their own receptor and response specificity. In this context, the brain is especially complex since it contains a great number of different neurones. Yet, neurones that are...

Gastric Emptying

Since increased membrane surface area and decreased thickness of the absorbing membrane favor the small intestine rather than the stomach as the primary site for drug Stomach pH 1-3 Dudodenum pH 5-7 Ileum pH 7-8 Figure 1 Diagrammatic representation of the complexity of the gastro-intestinal tract, with an impression (left) of the size of the GI tract in an adult. The average pH values of the stomach, duodenum, and ileum are shown. The small intestine contains bile salts and other agents, which...

Effect of pH

If the drug has either weakly acidic or basic (or both) groups in its structure such as a carboxylic acid or primary amine, respectively, then these will be affected by pH in aqueous media. For a weak acid, alkaline pH values will promote dissociation or ionization of the acid group creating a charged molecule, which will increase solubility, through improved hydrogen bond formation, with the converse applicable to weak bases. This can be represented by the following equations for a...

Physicochemical drug interactions and incompatibilities

10.1 pH effects in vitro and in vivo 395 10.7 Adsorption of drugs 414 10.2 Dilution of mixed solvent systems 401 10.8 Drug interactions with plastics 417 10.3 Cation-anion interactions 402 10.9 Protein binding 419 10.4 Polyions and drug solutions 405 Summary 425 10.5 Chelation and other forms of Appendix 425 complexation 405 References 429 10.6 Other complexes 410 Further reading 430 This chapter deals with some practical consequences of the physical chemistry of drugs -particularly their...

Ladme Scheme In Pharmacology

Figure 1.2 Relationship between the pharmacokinetic, link, and pharmacodynamic models. Figure 1.2 Relationship between the pharmacokinetic, link, and pharmacodynamic models. 1.3 LADME Scheme and Meaning of Pharmacokinetic Parameters The frequently used acronym LADME, which stands for liberation, absorption, distribution, metabolism, and excretion, broadly describes the various biopharmaceutical processes influencing the pharmacokinetics of a drug. Since each of aspect of LADME can influence the...

Sodium Cocoyl Isethionate

Sodium cocoyl isethionate (SCI) is a mild primary surfactant with a dense, luxurious foam. It is mild on the skin, and non-drying. Sodium cocoyl isethionate can be combined with other surfactants to make an elegant creamy shampoo and body wash. It can be used as the only surfactant in a cream or solid bar cleanser. In both hair and skin care applications this surfactant creates an elegant feel during use and a conditioned afterfeel. Physical Form Easy to handle white noodles.

Our Body's Instinctive Organ Systems

Did you know that there are a total of 11 organ systems that make up our bodies Each of these organ systems have very specific roles in the body, but they also work together in a fascinating way in order to keep us going. In this article, we will identify these 11 systems, as well as highlight the main organs involved in each and what their roles are. Integumentary System The integumentary system is the external covering of our body, our skin.

Discovery and Preclinical Development Candidate Selection

The preclinical development stage encompasses aspects of both drug discovery and drug development. The process to identify a potential drug candidate is an iterative one, as discovery scientists strive to synthesize candidate compounds with appropriate activity and maximal potency at the intended target, maximal safety profile, and desirable ADME properties. The definition of desirable properties will be variable considering the therapeutic target and class of compounds, but typical goals are...

PH Measurements

Under aqueous conditions, the concentration of hydrogen ion in solution is usually expressed in terms of the hydrogen ion concentration or activity, or in terms of pH units. The pH of a non-aqueous solution or co-solvent solution is more difficult to measure, since pH only relates to purely aqueous conditions. The pH of a water miscible solution can be measured with an electrode, however interpretation of the pH value must be done with care. First, the glass electrode may be off by as much as a...

Drug Absorption Assessment Using In Vitro Data

When MAD is estimated with in vivo data, either the in vivo absorption rate constant, or the drug in vivo intestinal permeability is required for the calculation. However, during early stages of drug discovery and development, in vivo data are usually unavailable. The challenge is to optimize the process for selecting compounds to evaluate in vivo human studies based on in vitro data. Fortunately, drug permeability in Caco-2 cells and drug solubility are routinely screened in the pharmaceutical...

The importance of water solubility

A drug's solubility and behaviour in water is particularly important since the cells in our bodies normally contain about 65 per cent water. In living matter water acts as an inert solvent, a dispersing medium for colloidal solutions and a nucleophilic reagent in numerous biological reactions. Furthermore, hydrogen bonding and hydrophobic interactions in water influence the conformations of biological macromolecules, which in turn affect their biological behaviour. Water solubility also makes...

The effect of pH on the solubility of acidic and basic drugs

Aqueous biological fluids are complex systems that contain a variety of different solutes. These species will have an effect on each other's relative solubilities and the solubilities of drugs or xenobiotics introduced into the fluid. They also control the pH of the fluid, which is of considerable importance to the bioavailability of acidic and basic drugs. An acidic or basic pH will either enhance or reduce the ionisation of these drugs with subsequent changes in their solubility and...

Schild Analysis

Experimentally, a KB is estimated by studying the interaction of an agonist and antagonist over a wide range of antagonist concentrations (the wider, the better). This is necessary because drugs that are not reversible competitive antagonists may appear to be so within a narrow range of concentrations. If the antagonist is truly competitive, it should produce parallel rightward displacement i.e., no change in midpoint slope (m) occurs of the E log A curves with no change in the maximal response...

Competition binding

Radioligands are fairly expensive and only very few of them are specific enough for the purpose of receptor identification. Fortunately, radiolabelling of a drug is not strictly required for determining its affinity for a given receptor. This parameter can indeed be determined on basis of the drug's ability to compete with a specific radioligand for binding to that receptor. These competition binding experiments are now widely used by pharmacologists as a screening tool to evaluate the affinity...

Vessel Due F

Sulodexide Antithrombotic drugs Vessel Due F ampoules Each ampoule contains Sulodexide 600 LSU Excipients sodium chloride, water for injection.Vessel Due F capsules Each capsule contains Sulodexide 250 LSU Excipients Sodium lauryl sarcosinate, Precipitated silica, Triglycerides, gelatine, glycerol, sodium ethyl p-oxybenzoate, sodium propyl p-oxybenzoate, titanium dioxide E171 and red iron oxide E172.

The Higuchi Model

Q (t) A D (2co cs) Cst, Co Cs, Figure 4.1 The spatial concentration profile of drug (solid line) existing in the ointment containing the suspended drug in contact with a perfect sink according to Higuchi's assumptions. The broken line indicates the temporal evolution of the profile, i.e., a snapshot after a time interval At. For the distance h above the exposed area, the concentration gradient (co cs) is considered constant assuming that Co is much higher than cs. Figure 4.1 The spatial...

Steric Features Of Drugs

Regardless of the ultimate mechanism by which the drug and the receptor interact, the drug must approach the receptor and fit closely to its surface. Steric factors determined by the stereochemistry of the receptor site surface and that of the drug molecules are, therefore, of primary importance in determining the nature and the efficiency of the drug-receptor interaction. With the possible exception of the general anesthetics, such drugs must possess a high structural specificity to initiate a...

PLCy1 Signaling

When phosphorylated, Y785 on TrkA and analogous sites on TrkB and TrkC bind PLC-y1, which is then activated through phosphorylation by the Trk receptor kinase (11) (Figure 3). Activated PLC-y1 hydrolyses PtdIns(4,5)P2 to generate inositol tris-phosphate (IP3) and diacylglycerol (DAG). IP3 promotes release of Ca2+ from internal stores, which results in activation of enzymes, such as Ca2+-regulated isoforms of protein kinase C and Ca2+-calmodulin-regulated protein kinases. DAG stimulates...

An Effort to Protect Yourself from Chemtrail Poisoning

An ounce of prevention is worth a pound of cure. Such is Ben Franklin's saying. How true it is He was talking about fire prevention, but the analogy can surely be applied to health. Especially when it comes to heavy metal and chemical exposure, the body's immune, nervous and endocrine systems may likely be worn down faster than therapies can build them back up, though there is some individual variation (see quote at the conclusion of this article).

The Endocrine System of Fish

To fully understand how these pollutants can affect fish at very low levels, it is necessary to outline very briefly how the endocrine system works. It is a control system of the body which responds to internal and external signals to maintain the body in a chemical equilibrium, to regulate sexual development and the seasonal reproductive cycles, and to evoke a stress response to external threats. At its core are the hypothalamus and pituitary, which respond to neural signals from the brain and...

Calcineurin Inhibitors

Perhaps the most effective immunosuppressive drugs in routine use are the calcineurin inhibitors, cyclosporine and tacrolimus, which target intracellular signaling pathways induced as a consequence of T-cell-receptor activation. Although they are structurally unrelated and bind to distinct molecular targets, they inhibit normal T-cell signal transduction essentially by the same mechanism (see Figure 52-1). FIGURE 52-1 Mechanisms of action of cyclosporine, tacrolimus, and sirolimus on T cells....

The Antitussive Action Of Opioids Blockade Of Cough Reflex

Each cough involves a complex reflex arc beginning with the stimulation of sensory nerves that function as cough receptors. There is evidence, primarily clinical, that the sensory limb of the reflex exists in and outside of the lower respiratory tract. Although myelinated, rapidly adapting pulmonary stretch receptors (RARs), also known as irritant receptors, are the most likely type of sensory nerve that stimulates the cough center in the brain, afferent C-fibers and slowly adapting pulmonary...

DUROS Implant Technology for Chronic Pain Treatment

Just as ALZA Corporation's oral and transdermal technologies can improve therapy by controlling drug delivery over hours or days, the DUROS was designed to bring the same benefits of continuous therapy for up to 1 year. DUROS technology is the platform for an implantable drug-dispensing osmotic pump Chronogesic . The system is shaped as a small rod with titanium housing, which can be as small as a matchstick, designed to release drugs Fig. IV-37 . The water drawn into the engine compartment...

Powder Filling

The types of filling machines available for filling hard-shell capsules and their operating principles have been the subject of a number of reviews (30,58-63). Four main dosing methods may be identified for powder filling At one time, nearly all capsules were filled by means of semiautomatic equipment wherein the powder is driven into the capsule bodies by a rotating auger, as exemplified by the type 8 machines (Fig. 7). The empty capsule bodies are held in a filling ring, which rotates on a...

Sources of ATP for muscle contraction

Skeletal muscle uses only ATP as a source of energy for contraction. However, intracellular stores of ATP are quite limited. In fact, the amount of ATP normally found in skeletal muscle is enough to sustain only a few seconds of contraction. Therefore, metabolic pathways to form additional ATP are needed.

Craig Plots And The Topliss Decision Tree

Various schemes have been developed to exploit the Hansch relationships. In the first, known as the Craig plots, p is plotted against s for a series of different substituents see Scheme 7 . This has the effect of highlighting substituents with potentially similar effects on the Hansch equation. The second scheme is known as the Topliss decision tree. It is based on using the change in biological activity arising from inserting one substituent to suggest the next substituent in order to maximize...

Opioids And Gastrointestinal Inhibition Constipation

Following oral ingestion, but also after the systemic administration, opioids also bind to selective receptors located within the intestinal tract. The physiological significance of peripherally located opioid binding sites within the intestine is that of regulation of the propulsive transit. The intestine with a total surface of nearly 400 m2 is an underestimated important anatomical site as it has a high accumulation of neuronal tissue, which has been termed the enteral nervous system (ENS),...

Reaction Of Naphthalene With Carboxylic Acid

Diazonium salt formation Primary arylamines react with nitrous acid (HNO2) to yield stable arenediazonium salts, Ar N+ NX . Alkylamines also react with nitrous acid, but the alkanediazonium salts are so reactive that they cannot be isolated. Aniline is a primary arylamine, and it reacts with nitrous HNO2 to yield stable benzene diazonium salt (Ph N+ NX ). The drive to form a molecule of stable nitrogen gas causes the leaving group of a diazonium ion to be easily displaced by a wide variety of...

Beckett And Casy Model

T-butyl Buprenorphine CH3 Diprcnorphine * Actually hydrog nation is carried out before the Grignard reaction. ** Cyanogen bromide N-demethylatcs the compounds. *** NaOH selectively cleaves the phenolic ether. Figure 5-12. The oripavine compounds. not to affect the tertiary OH) resulted in corresponding phenolic compounds with extremely high potency. The most astounding compound, etorphine (Fig. 5-12), revealed potencies up to 10,000 times that of morphine in animal models. It is interesting...

The Allosteric Ternary Complex Model Radioligand Binding And Affinity

In order to design and critique methods for screening for allosteric modulators, it is necessary to understand the macromolecular basis of the interaction of allosteric ligands with a GPCR. The simplest model of a three-way interaction between a GPCR, an orthosteric ligand, and an allosteric modulator is the allosteric ternary complex model (ATCM) proposed by Stockton et al. 13 , which is illustrated in Fig. 12.1. Both an orthosteric ligand (A) and an allosteric ligand (B) can interact with a...

Schild Analysis in heterogeneous Receptor Systems

As outlined above, a relatively common experimental finding in Schild analyses is a nonlinear plot with an inflexion, the result of an agonist activating two distinct receptor types mediating the same response, for which the antagonist under study has differential affinities. Lemoine and Kaumann (36) extended Eq. (11) to produce a model that mathematically describes such data for the specific case where an agonist has high efficacy at both receptor types (Q and R). The equation shown below is...

Atropine Is A Racemic Mixture Whereas Hyosciamine Is Levo Compound

Atropine occurs in the form of optically inactive, white, odorless crystals possessing a bitter taste. It is not very soluble in water (1 460, 1 90 at 80 C) but is more soluble in alcohol (1 2, 1 1.2 at 60 C). It is soluble in glycerin (1 27), in chloroform (1 1), and in ether (1 25). Saturated aqueous solutions are alkaline in reaction (pH 9.5). The free base is useful when nonaqueous solutions are to be made, such as in oily vehicles and ointment bases. Atropine has a plasma half-life of...

Treatment Of IgM Paraproteinemic Neuropathy

The rationale for treating IgM paraproteinemic neuropathy is based on the assumption that the paraprotein plays an etiological role in the neuropathy. This evidence is particularly compelling in the cases associated with antibodies directed against MAG. Current treatment strategies include conventional immunosuppressive or immunomodulating regimens such as steroids, intravenous immunoglob-ulin, plasma exchange, alkylating agents or other chemotherapeutic drugs such as cyclophosphamide or...

The Cox1 Cox2 Concept

Most of the biological data suggested that Cox-2 was the predominant inflammatory species, and by implication, the best target for NSAIDs. So was Cox-2 inhibition the true therapeutic modality of NSAIDs If so, Cox-1 inhibition might account for the side effects, such as gastric irritation and depression of platelet aggregation. This was the notion advanced by more than one group (26, 27) which came to be known as the Cox-2-bad Cox-1-good hypothesis. If true, then the obvious corollary was that...

CCL2 MCP1 and CCR2

Recruitment of mononuclear leukocytes to the atherosclerotic lesion is a critical step in both the initial development and further progression of the plaque. Monocyte chemoattractant protein (MCP)-1, CCL2, is a member of the CC chemokine family and is a potent monocyte and lymphocyte chemoattrac-tant (22). It is produced by various cell types in the arterial wall including endothelial cells (23,24), smooth muscle cells (25), and fibroblasts (23). CCL2 initiates signal transduction through...

Nitrogen Mustards

The nitrogen mustards are compounds that are chemically similar to sulfur mustard or mustard gas developed and used in World War I. The term mustard comes from the similarity in the blisters produced by the compound and those seen upon exposure to the oil of black mustard seeds. Investigation of sulfur mustard revealed that it possessed an-tineoplastic properties but because the compound existed as a gas at room temperature, handling and administration of the material were difficult. Conversion...

Bidentate Ligands

Two monodentate ligands can be combined to one bidentate ligand.According to the chelate effect, the complexes are expected to be even stabler. This is not so crucial since it is almost impossible to replace even monodentate ligands but more importantly, the rate of coordination is expected to be faster. Hence, the ligand concentration to achieve quantitative labelling or complex formation will be lower. In terms of preference, bidentate ligands are similar to mono-dentate ones. Many possible...

Drug action that affects the structure of cell membranes and walls

Most drugs act on the enzymes and receptors found in cell membranes and walls. These aspects of cell membranes are discussed in succeeding chapters. However, a number of drugs act by blocking ion channels, disrupting the structure of the cell membranes and walls or inhibiting the formation of cell membranes and walls. For example, the venoms of both the eastern diamondback rattlesnake and the Indian cobra contain the enzyme phospholipase A2. This enzyme catalyses the hydrolysis of the C2 fatty...

Nitrofurantoin

Nitrofurantoin (furadantin, macrobid, others) is a synthetic nitrofuran that is used to prevent and treat urinary tract infections. Bacteria reduce nitrofurantoin to toxic products that apparently mediate cell damage. The antibacterial activity is higher in acidic urine. Nitrofurantoin is absorbed rapidly and completely from the GI tract. Antibacterial concentrations are not achieved in plasma at recommended doses because the drug is eliminated rapidly. The plasma t 2 is < 1 hour 40 is...

Tributyl Phosphate

Tributyl phosphate is a plasticizer and or solvents for cellulose esters, lacquers, plastic and vinyl resins. It is used as a solvent extractant of rare earth metals from ores. It is used as a heat exchange media. It is also used as a pigment grinding assistant and antifoam agent. This is an organic phosphor compound, which forms stable, hydrophobic complexes with metals such as uranium. The produced complexes dissolve easily in organic solvents and supercritical CO2.

Steroid Biosynthesis

Steroid hormones in mammals are biosynthesized from cholesterol, which in turn is made in vivo from acetyl-coenzyme A (acetyl-CoA) via the mevalonate pathway. Although humans do obtain approximately 300 mg of cholesterol per day in their diets, a greater amount (about 1 g) is biosynthesized per day. A schematic outline of these biosynthetic pathways is shown in Figure 25.5. Conversion of cholesterol to pregnenolone is the rate-limiting step in steroid hormone biosynthesis. It is not the...

Central sites of action of caffeine

The widespread use of caffeine-containing beverages has focused research on the mechanisms underlying the central effects of caffeine.1-3 While the effects of moderate doses of caffeine on behavior are complex, it appears likely that blockades at A1- and A2A-adenosine receptors are the primary molecular sites of action for caffeine. There are at least four types of adenos-ine receptors in brain.4,5 The A1-class can be inhibitory to adenylate cyclase, stimulatory to potassium channels,...

Freeman Ketogenic Diet

The Ketogenic Diet A Treatment for Epilepsy, 3rd ed. Demos, New York, 2000. 2. Musa-Veloso K, Likhodii SS, Cunnane SC. Breath acetone is a reliable indicator of ketosis in adult volunteers consuming ketogenic meals. Am J Clin Nutr 2002 76 65-70. 3. Freund G. The calorie deficiency hypothesis of ketogenesis tested in man. Metabolism 1965 14 985-990. 4. Livingston S. Dietary treatment of epilepsy. In Comprehensive Management of Epilepsy in Infancy, Childhood and...

Ketone Bodies Levels and Metabolic Roles

Figure 2 outlines the biochemical pathways by which ketone bodies are generated. P-Hydroxybutyrate is the most frequently measured ketone body. The concentration of Fig. 1. Both fasting and the ketogenic diet induce a number of common changes in the body. These include an elevation of ketone bodies in the blood and brain, a decrease in glucose utilization, and a shift in electrolytes and hormones. The identification of specific changes resulting in anticonvulsant effects has been challenging....

Advantages Of Maintenance Phase Infusions Compared To Intermittent Bolus Dose

During an infusion, the effect-site concentration mirrors plasma concentration, except following changes in rates or following supplemental boluses. This is due to the fact that either from a high loading dose or a long infusion time (Table III-7), the different compartments of the three-compartment model have been filled. Therefore, the kinetics are now mostly on the lower end of the decay curve (i.e., beta slope). Indications for the intravenous infusion of an opioid for anesthesia are as...

Principles of Pharmacokinetics and Pharmacodynamics

PRINCIPLES OF PHARMACOKINETICS AND PHARMACODYNAMICS INTRODUCTION Pharmacokinetics is defined as the study of the time course of drugs and their metabolites through the body. Pharmacodynamics is defined as the study of the time course and intensity of pharmacological effects of drugs. A convenient lay description of these terms is that pharmacokinetics describes what the body's physiology does to a drug, and pharmacodynamics describes what a drug does to the body. Although clinicians are more...

Digitalis purpurea L

Species of Digitalis were used by English herbalists and led to the discovery of the cardioactive glycoside digoxin used in medicine today. The English botanist and physician William Withering is credited with identifying digitalis as the active ingredient of a traditional herbal preparation for the treatment of dropsy congestive heart failure . Withering's identification was made after a meticulous microscopic examination of the herbal mixture. His use of Digitalis for the treatment of...

Secondary Stems of Dicots and Gymnosperms

Secondary growth commences with the formation of the vascular cambium, arising first in the vascular bundles and then extending laterally between bundles to form a circumferential ring when viewed in transverse section. Considered in three dimensions, the vascular cambium is an actively dividing cylinder of cells that is bifacial, producing secondary xylem (wood) to the interior and secondary phloem to the exterior and thereby increasing the diameter of the plant axis. In the vascular bundles,...

Calcium Pantothenate, Pantothenic acid, Vitamin B5

Vitamin B5 is also known as pantothenic acid or calcium pantothenate. This is a water soluble vitamin which is found in the cells. Vitamin B5 is produced in the intestines by bacteria and is known to place a role on preventing depression. Vitamin B5 is necessary for the release of energy from carbohydrates, the synthesis and degradation of fatty acids and other acetylation reactions.

The Top 10 Healthiest Seeds on Earth

They come in all different sizes, shapes and colours. The seed is an embryonic plant itself and the origin of nutrition. A plant goes to great lengths to produce each seed and fill it with high concentrations of vitamins, minerals, proteins, essential oils and dormant enzymes. If you're looking for a high quality, nutritious and filling snack, seeds are tough to beat. Let's look at the ten healthiest seeds on Earth and how to consume them.A seed is life. It is a living food.

Biochemical classification of hormones

Hormones are classified into three biochemical categories (see Table 10.1) Steroid hormones are produced by the adrenal cortex, testes, ovaries, and placenta. Synthesized from cholesterol, these hormones are lipid soluble therefore, they cross cell membranes readily and bind to receptors found intracellularly. However, because their lipid solubility renders them insoluble in blood, these hormones are transported in the blood bound to proteins. Furthermore, steroid hormones are not typically...

Regulation of ventilation

The rate and depth of breathing are perfectly adjusted to meet the metabolic needs of the tissues and to maintain a PO2 of 100 mmHg, a PCO2 of 40 mmHg, and a pH of 7.4 in the arterial blood. Breathing is initiated spontaneously by the central nervous system and occurs in a continuous cyclical pattern of inspiration and expiration. The three major components of the regulatory system for ventilation are Medullary respiratory center Receptors and other sources of input Effector tissues...

How to Remove Lead from your Body

There are six minerals that are considered non-essential toxic minerals. These are aluminum, mercury, cadmium, silver, gold and lead. Exposure to lead, which is considered a heavy metal, is almost impossible to avoid in an urban society. Among the most common exposures to lead are inhaling exhaust fumes, cigarette smoke and industrial airborne pollutants, paint in homes built prior to 1978, and unfiltered tap water.

Reactivity of Asparagine and Glutamine Residues

Asparagine residues (and glutamine residues, see below) are sites of particular instability in peptides. As will be exemplified below, rates of degradation at asparagine residues are markedly faster (tenfold and even much more) than at aspartic acid residues. As reported, the t1 2 values for the internal asparagine in a large number of pentapeptides ranged from 6 to 507 d under physiological conditions of pH and temperature, while those of internal Gln ranged from 96 to 3409 d 6 . Degradation...

Glucocorticoids With Very Little Or No Salt Retention

Most of the key differences between the many GCs with minimal salt retention see Fig. 25.29 have been summarized in Tables 25.6 and 25.7. The tremendous therapeutic and, therefore, commercial importance of these drugs has stimulated the proliferation of new compounds and their products. Many compounds also are available as salts or esters to give the complete range of therapeutic flexibility illustrated in Figure 25.29. When additional pertinent information is available, it is given below the...

Drug Sulfate Conjugation

(PAPS) Figure 3.13 Formation of PAPS and sulfate conjugates. principal route of metabolism in humans. For many phenols, however, sulfoconjugation may represent only a minor pathway. Glucuronidation of phenols is frequently a competing reaction and may predominate as the conjuga-tive route for some phenolic drugs. In adults, the major urinary metabolite of the analgesic acetaminophen is the O-glucuronide conjugate, with the concomitant O-sulfate conjugate being formed in small amounts.364...

Chloramphenicol

Chloramphenicol is a broad-spectrum antibiotic. It is active against a wide variety of organisms. It interferes with the production of proteins that the bacteria need to multiply. This inhibits the ability of the bacteria to grow and therefore stops the spread of the infection. Chloramphenicol is effective against a wide variety of microorganisms, but due to serious side-effects (e.g.

Methotrexate Mechanism Of Action

Methotrexate inhibits folate metabolism by preventing methylenetetrahydrofolate reductase from converting 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate thus inhibiting thymidylate synthase conversion of dUMP to dTMP. DNA replication is effectively decreased by the diminution of dTMP availability. As shown in Fig. 2, multiple enzymes mediate the folate cycle. Thus, genetic variation in these enzymes may Fig. 1. Genetic factors impacting chemotherapy efficacy and toxicity. Fig. 1....

Phantom sensation

Phantom sensation is experienced by almost everyone who undergoes limb amputation, but it rarely represents a clinical problem. Immediately after the amputation, the phantom limb often resembles the preamputation limb in shape, size, and volume.11,1922 2354 The sensation can be very vivid and often includes feelings of posture and movement. The phantom sensation may fade over time. Richardsen et al.26 prospectively studied phantom phenomena in 52 lower amputees. At six-months follow up,...

Agonists Antagonists Their Potency And Mode Of Action

Based on their interactions with the various receptor subtypes, opioid compounds can be divided into agonist, agonist antagonist, and antagonist classes (Table II-4). By definition an agonist is a drug that has affinity for and binds to cell receptors to induce changes in the cell that stimulate physiological activity. The agonist opioid drugs have no clinically relevant ceiling effect to analgesia. As the dose is raised, analgesic effects increase in a log linear function, until either...

Gonadotropinreleasing Hormone And Gonadotropins

LH and FSH were named initially based on their actions on the ovary. These pituitary hormones, together with the related placental hormone hCG, are collectively referred to as the gonadotropins because of their actions on the gonads. The regulation of gonadotropin secretion is described in detail in Chapters 57 and 58. LH and FSH are synthesized and secreted by gonadotropes hCG is synthesized the syncytiotrophoblast of the placenta. Pituitary gonadotropin production is stimulated by GnRH and is...

Mechanics of breathing

The mechanics of breathing involve volume and pressure changes occurring during ventilation that allow air to move in and out of the lungs. Air will move from an area of high pressure to an area of low pressure. Therefore, a pressure gradient between the atmosphere and the alveoli must be developed. This section will explain how changes in thoracic volume, lung volume, and pulmonary pressures occur in order to cause the pressure gradients responsible for inspiration and expiration. Thoracic...

Structure and function of plasma membrane

The major components of the plasma membrane include The basic structure of the plasma membrane is formed by phospholipids (Figure 2.1), which are one of the more abundant of the membrane components. Phospholipids are amphipathic molecules that have polar (water-soluble) and nonpolar (water-insoluble) regions. They are composed of a phos-phorylated glycerol backbone, which forms a hydrophilic polar head group and a nonpolar region containing two hydrophobic fatty acid chains. In an aqueous...

Rapid Mixing Quenching Devices Permit Kinetic Analysis of a Wide Range of Chemical Reactions

Although rates are most conveniently assayed when attended by large changes in the UV visible or fluorescence spectrum, the majority of enzyme-catalyzed reactions do not generate any observable change in their electronic spectrum. In such cases, it is necessary to purchase or prepare substrates containing one or more radioactive atoms so that changes in substrate depletion and or product accumulation can be analyzed. The experimenter uses a rapid mix quench apparatus, a device containing two or...

Transduction mechanisms

The discovery of a-gustducin in the laboratory of Robert F. Margolskee was a milestone in the elucidation of taste transduction mechanisms (McLaughlin et al. 1992). This G-protein subunit, which is closely related to transducin, the G protein of visual sensory transduction, was specifically detected in a subset of taste receptor cells of rodents and humans (McLaughlin et al. 1992 Takami et al. 1994), making it an attractive candidate for transducing taste stimuli. In fact, the participation of...

Limited access to the CNS

A2-receptors located in regions of the brain such as the nucleus tractus solitarius. Stimulation of these a2-receptors brings about a decrease in sympathetic outflow from the CNS, which in turn leads to decreases in peripheral vascular resistance and blood pressure.20,38 Bradycardia is also produced by clonidine as a result of a centrally induced facilitation of the vagus nerve and stimulation of cardiac prejunctional a2-receptors.39 These pharmacological actions have made clonidine quite...

Ankle Block

Innervations to the ankle involves five major nerve branches of the foot as indentified in Table 20.12. An ankle block is basically an infiltration block. Peripheral nerves blocked during an ankle blockade are derived from the terminal branches of the sciatic nerve (deep and superficial peroneal and sural nerves) and one from the distal branch of the femoral nerve (saphenous nerve). Motor blockade is not often needed for surgeries carried out under the influence of an ankle blockade. Table...

Metabolism Of Chlorpromazine

Figure 12.6 Some metabolic pathways for chlorpromazine. Figure 12.6 Some metabolic pathways for chlorpromazine. Promazine. Promazine, 10- 3-(dimethylamino) propyl-(phenothiazine monohydrochloride (Sparine), was introduced into antipsychotic therapy after its 2-chloro-substituted relative. The 2H-substituent vis- -vis the 2Cl substituent gives a milligram potency decrease as an antipsychotic, as encompassed in Gordon's rule. Tendency to EPS is also lessened, which may be significant, especially...

Vasoactive substances

Substances released from many cells and tissues in the body, including the endothelium lining blood vessels, endocrine glands, and myocytes in the heart, may affect vascular smooth muscle tone. These substances may stimulate this muscle to cause vasoconstriction or inhibit it to cause vasodilation. As expected, vasoconstriction will increase TPR (and therefore MAP) and vasodilation will decrease TPR (and therefore MAP). Vasoconstrictors. Many substances produced in the human body cause...

Neurohypophyseal Hormones Oxytocin Vasopressin

The posterior pituitary neurohypophysis is the source of vasopressin, oxytocin, a- and jS-MSH, and coherin. The synthesis, transport, and release of these hormones have been reviewed by Brownstein.32 Vasopressin and oxytocin are synthesized and released by neurons of the hypothalamic-neurohypophyseal system. These peptide hormones, and their respective neurophysin carrier proteins, are synthesized as structural components of separate precursor proteins, and these proteins appear to be partially...

ABC and SLC Transporters

ATP-binding cassette ABC transporters and solute carrier SLC transporters are the two main classes that drug transporters can be categorized into. The ABC family of transporters requires ATP hydrolysis to transport substrates across membranes. Therefore, ABC transporters are primarily active transporters. Notable examples of ABC transporters include P-gp, multidrug resistance-associated protein MRP , and breast cancer resistance protein BCRP . In contrast to ABC transporters, SLC transporters...

High Throughput Screening and Virtual Screening Entry Points to Drug Discovery

Eglen, Gisbert Schneider, Hans-Joachim B hm The goal of pharmaceutical research is to discover new molecules with a desired biological activity that are useful in the efficient and safe treatment of human diseases. The discovery process is quite complex and can be divided into several steps. The first step is normally the selection of a molecular target, e.g. an enzyme or a receptor that is associated with the disease. This selection process is still primarily driven by searching...

High Density Assay Plates for HTS and Multidimensional Compound Profiling

A broad variety of assays with different detection technologies have been developed for HTS and for multidimensional profiling of the active compounds identified by HTS. Heterogeneous assays are multistep assays that can involve multiple liquid additions, incubations, washings, liquid transfer from a first assay plate to a second assay plate, filtration, and reading of the signal. Homogeneous assays, also called mix-and-measure assays, are one-well assays without wash-, filtration-, or transfer...

Biology of G Protein Coupled Receptors

GPCRs are characterized by seven transmembrane domains oriented with an extracellular N terminus and an intracellular C terminus. They are activated by a diverse array of extracellular substances including biogenic amines, neuropeptides, hormones, chemokines, odorants, amino acids, free fatty acids, photons, and metabolic intermediates (Pierce, Premont, and Lefkowitz 2002 He et al. 2004 Wise, Jupe, and Rees 2004). The process of GPCR activation is initiated when an agonist binds to its...

Assay Types For Gpcrs IN uHTS 1321 Radioligand Displacement Assays

The radioligand displacement assay was one of the earliest assays used to study GPCRs. For nearly 50 years, the radioligand displacement assays, also known as competition binding assays, were used by the pharmaceutical industry as a preferred screening method to identify candidate drug molecules capable of binding to GPCRs, the largest group of pharmaceutical drug targets involved in a variety of physiological disorders. These assays, performed with purified membrane preparations from cells 13...

How To Number The Structure Of Reserpine

Figure 16.7 Mechanism of -receptor-mediated signal transduction. been proposed that the adrenergic agonist-binding site is within the TM-spanning regions, whereas the cytoplasmic regions of the receptor interact with the Gs protein. Specifically, aspartic acid residue 113 in transmembrane region III TM-III acts as the counterion to the cationic amino group of the adrenergic agonist. This aspartic acid residue is found not only in a comparable position in all the other adrenoceptors but also in...

Disadvantages of Metabolic Reduction Assays

Some of the major disadvantages of both the tetrazolium and resazurin reduction assays are related to the requirement to incubate a substrate with viable cells for a sufficient time to generate a measurable signal. This is a very important feature to consider when designing assays for HTS. In addition to the extra plate handling steps needed to return the cells to a 37 C incubator, the extended incubation of the detection reagents with viable cells increases the possibility of undesirable...

Breast Cancer Resistance Protein Bcrp Abcg2

The ABC transporter BCRP was first cloned from a doxorubicin-resistant MCF7 breast cancer cell line (MCF-7 AdrVp) by Doyle et al. (1998). Subsequently, other groups cloned the BCRP cDNA sequence from other sources and designated the gene either MXR (mitoxantrone resistance protein) or ABCP (placental ABC protein) (Allikmets et al., 1998 Maliepaard et al., 1999). Since structural and sequence homology revealed that BCRP belongs to the ABCG gene subfamily, the Human Genome Nomenclature Committee...

Lorazepam Before Coitus

Those who have undergone bilateral oophorectomy with hysterectomy. Women with hepatic disease, a history of breast cancer, uncontrolled hyperlipidemia, acne, or hir-sutism should not be treated. Baseline free and total testosterone levels, liver function tests, and lipid profile should be obtained prior to initiating therapy. Liver function tests and lipids should be monitored every 6 months during therapy. Women should be current on cervical and breast screening. Yohimbine has been reported to...

Pharmacodynamic Variation

Pharmacology holds that a drug must be present at receptor sites to produce its characteristic response. The magnitude of the response depends on the concentration of the drug at the receptor sites (pharmacokinetics) as well as the number of receptors and the ability of the cells to respond to receptor occupation (phar-macodynamics). Pharmacodynamics contributes, independent of pharmacoki-netics, to the total individual variability in drug response. Studies that combine measures of...

Orotic Acid Vitamin B13

Vitamin B13 is a compound from distillers consisting of dried solubles. It was later identified as orotic acid, an intermediate in pyrimidine metabolism. It is recognized as a treatment for MS (multiple sclerosis) and is dispensed under the name of calcium orotate (an essential growth factor in rats). Good sources are root vegetables and whey. Vitamin B13 is primarily used for metabolization of folic acid and vitamin B12.

Dissolution

The availability of a drug in the body depends on its ability to dissolve in the gastrointestinal (GI) fluids. If the rate of dissolution is the rate-limiting step in drug absorption, any factor affecting the dissolution rate will have an impact on bioavailability. The dissolution rate of suspended, poorly soluble drugs according to the well known diffusion-layer model, modified Noyes-Whitney equation (Horter and Dressman, 1997 Nystrom, 1998) is as follows where D is the diffusion coefficient,...

Hansch Analysis

Hansch analysis is based on the attempts by earlier workers, notably Richardson (1867), Richet (1893), Meyer (1899), Overton (1901), Ferguson (1939) and Collander (1954), to relate drug activity to measurable chemical properties. Hansch and co-workers in the early 1960s proposed a multiparameter approach to the problem based on the lipophilicity of the drug and the electronic and steric influences of groups found in its structure.

Solid Dosage Forms Ocular Inserts

In earlier times, it has been reported that lamella or disks of glycerinated gelatin were used to supply drugs to the eye by insertion beneath the eyelid. The aqueous tear fluids dissolved the lamella and released the drug for absorption. The medical literature also describes a sterile paper strip impregnated with drug for insertion in the eye. These appear to have been the first attempts at designing a sustained-release ocular dosage form. In 1975, the first controlled-release topical dosage...

Bena expectorant

Clears chesty Cough Composition Each 5 ml contains Diphenhydramine Hydrochloride 14 mg Ammonium Chloride 135 mg Sodium Citrate 57.5 mg Sodium Benzoate as preservative 7.50 mg Pharmacology Diphenhydramine Hydrochloride, Ammonium Chloride and Sodium Citrate are readily and effectively absorbed from the gastrointestinal tract. Diphenhydramine Hydrochloride is extensively metabolished in the liver and excreted mainly as metabolites is the urine.

DNA Methylation X Inactivation and Genomic Imprinting

The effect of parenteral origin on gene expression arises through a mechanism known as genomic imprinting.9 Experimental evidence for such an effect in mammals was first reported by McGrath and Solter,26 who demonstrated the failure of mouse embryos derived from purely maternal or paternal genomes to develop beyond implantation. There followed a growing realization that memories of the maternal and paternal genes were permanent, persisting throughout the development and life of the individual,...

The Pathology Of Alzheimers Disease

Pathologically, AD consists of two classical predominant neuropathological lesions. Neuritic (senile) plaques contain extracellular deposits of the amyloid p-proteins (Ap). A portion of these deposits occur as clumps of insoluble amyloid fibrils,16 but these are intermixed with an as-yet poorly defined array of non-fibrillar forms of this peptide.

Sleepwalking

It can be alarming to discover your child is a sleepwalker but it's seldom something to worry about, provided you take care the sleeping child has a safe environment in which to move. Sleepwalking is generally a much misunderstood quirk of human behaviour. Contrary to popular myth, those who walk or get up and about in their sleep are not acting out their dreams. The phenomenon is common in childhood - it has been estimated that one in five children sleepwalk occasionally.

Role Of Cmet Ckit And Egfr

C-Met signaling (Met-HGF SF) has been well studied in various forms of human cancers. c-Met has been found to have a number of biological effects related to the cytoskeleton, for example scattering, cell motility, invasion, migration, and finally metastasis. HGF SF-Met signaling plays an important role in lung cancer (solid tumor) and can invade and metastasize using this signaling pathway (Figure 5.2).24 SCF HGF-Met signaling significantly increases the motility of epithelial cells, which play...