By P. Ugolf. Texas Tech University.
Peter Mansfeld showed how the radio signals could be mathematically analyzed purchase premarin 0.625 mg online, which made it possible to develop a useful imaging technique discount premarin 0.625mg visa. This snap-shot technique meant that in principle complete two-dimensional images could be achieved in extremely short times like 20 – 50 ms order premarin 0.625 mg free shipping. They are rapidly turned on and off (which causes that banging noise) buy 0.625 mg premarin free shipping, and the gradient magnets allow the scanner to image the body in slices. The transverse (or axial, or x-y) planes slice you from top to bottom; the coronal (x-z) plane slice you lengthwise from front to back; and the sagittal (y-z) planes slice you lengthwise from side to side. Y Coil Z Coil X Coil Transceiver Patient An illustration of the feld gradient coils. Mansfeld showed how the radio signals can be mathematically analyzed, and thus made the image possible. Echo-planar imaging allows T weighted im- 2 ages to be collected many times faster than previously possible. The electromagnets consist of a so- lenoid cooled down to about 4 K by liquid helium. At such temperatures superconduction is attained and it is possible to send large currents through the solenoid and thus get the large magnetic felds required. For parts of the body with bones it is dif- fcult to use x-rays to study the tissue around – because the bones absorb the x-rays much more than the tissue. This is a Lanthanide element (atomic number 64) that is paramagnetic and has the effect that it strongly decrease the T1 relaxation times of the tissues. These compounds are taken up by, and accumulate in, glycolytically active cells, such as rapidly dividing tumor cells. These compounds also bind to albumin in the blood, allowing for the assessment of blood volume at tumor sites prior to cellular uptake (similar to imaging with gadolinium), a valuable diagnostic indicator and tool for treatment response in its sur- roundings. Formation of ultrasound In 1880 Pierre Curie and his brother Jacques discovered that certain crystals (the socalled piezoelec- tric crystals) can produce a pulse of mechanical energy (sound pulse) by electrically exciting the crystal. Furthermore, the crystals can produce a pulse of electrical energy by mechanically exciting the crystal. This ultrasound physics principle is called the piezoelectric effect (pressure electricity). Crystalline materials with piezoelectric properties are quartz crystals, piezoelectric ceramics such as barium titanate or lead zirconate titanate. A device that converts one form of energy into another is called a “transducer” – and they can be used for production and detection of diagnostic ultrasound. We are not going into more details about the equipment here, but it is possible to use ultrasound tech- nique to produce pictures of the inside of the body. Since ultrasound images are captured in real-time, they can show the structure and movement of the body’s internal organs, as well as blood fowing through the blood vessels. Ultrasound imaging is a noninvasive medical test that helps physicians diagnose and treat medical conditions. A short history The origin of the technology goes back to the Curies, who frst discovered the piezoelectric effect. Attempts to use ultrasound for medical purposes startet in the 1940s when they used a contineous ultrasonic emitter to obtain images from a patient`s brain. The use of Ultrasonics in the feld of medicine had nonetheless started initially with it’s applications in therapy rather than diagnosis, utilising it’s heating and disruptive effects on animal tissues. An excellent review of the history of ultrasound can be found in the following address: http://www. The transducer is coupeled to the body by a gel and the pulse of ultrasound goes into the soft tissuse (speed of about 1500 m per second). The transducer will then sense the refected, weaker pulses of ultrasound and transform them back into electrical signals. These echoes from different organs are amplifed and processed by the receiver and sent to the computer, which keeps track of the return times and amplitudes. You can see how arms and legs of a fetus move, or see the heart valve open and close.
It significantly pro- longs the life of the patient buy 0.625 mg premarin mastercard, although it has a number of toxic effects cheap 0.625 mg premarin with mastercard. All types of protozoa are single-cell organisms that can adapt to various conditions premarin 0.625 mg with mastercard. These forms require different approaches when treat- ing patients that have protozoan infections trusted 0.625mg premarin. Protozoa are typical parasites that occupy host cells, multiply in them, and then destroy them. Prevention of protozoan diseases consists of controlling the spread of the disease, improv- ing sanitarial-hygenic conditions of life, receiving vaccinations, and treatment. It should be kept in mind that malaria is spread by mosquitoes, in particular by the bite of (female) Anopheles mosquito; leishmaniasis is spread through infected gerbils; trypanosome is spread by the tsetse fly; amibiasis and giardia are spread through food and water; and toxoplasmo- sis is spread through meat products and infected cats. Antimalarial drugs currently used for treatment for prophylaxis are mefloquine, primaquine, chloroquine, pyrimethamine, amodiaquin, quinine/quinidine, chloroguanide. The causative agents of malaria are plasmodia (Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale). Malarial plasmodia have two developmental cycles; an asexual cycle, which takes in the body of an infected person (schizogony); and a sexual cycle, which takes place in the body of the mosquito (sporogony). When a person is bit by a mos- quito, sporocytes that were formed in the blood of the mosquito (from male and female hematocytes) enter the body. These enter liver cells, where they form primary tissue sch- izonts, which grow, divide, and transform into merozoites. Merozoites then enter the blood of the person and diffuse into erythrocytes, where they develop further. After maturing in ery- throcytes, schizonts again divide and transform into merozoites. These merozoites are peri- odically released from the occupied erythrocyte cells and attack a new group of erythrocytes, starting the process over. Drugs for Treating Protozoan Infections destroyed and the merozoites enter the blood is expressed by an onset of malarial fever, which is referred to as the perierythrocytic form of malaria. This is when parasites in the mero- zoite stage of development remain in or enter the liver cells again. This restarts the erythrocytic cycle of development of plasmodia and the onset of relapse. Chemotherapy of malaria consists of affecting various stages of the life cycle of the par- asite. Antimalarial drugs are subdivided into three corresponding groups: those that have an effect on erythrocyte stage of the life cycle, those that destroy exoerythrocytic (or hepatic stage), and those that affect both stages simultaneously. Currently, aminoquinolines such as chloroquine and its analog (primarily for affecting the parasite during the erythrocyte stage), and pri- maquine (for affecting the parasite during the exoerythrocyte stage) are used to treat malaria. Recently, mefloquine, and a natural compound quinghaosu, as well as various antibiotics in combination with antimalarial drugs have begun to be used. Their most important structural character- istic is the type of substituent at C7 and C4 of the quinoline ring. It has been shown that an amine substituent is necessary at C4 of the quinoline ring, which can vary while retaining antimalarial activity of the compound; however, the necessary conditions for expression of antimalarial activity is the presence of a chlorine atom at C7 of the quinoline ring. The second group of drugs used during the erythrocyte stage of malarial infections is quinolinmethanol derivatives. This group includes mefloquine, pyranobenzodioxepin derivative isolated from the plant—quing- haosu, as well as cinchona alkaloids that are made from the bark of the cinchona tree, of which only quinine is still used for treating malaria. One of these ways consists of reacting 3-chloroaniline with ethoxymethylenmalonic ester to make (3-choroanilino)-methylenemalonic ester (37. Hydrolyzing this with sodium hydroxide gives 7-chloro-4-hydroxyquinolin-3-decarboxylic acid (37. Treating this with phosphorus oxychloride gives one of the desired components for synthe- sis of chloroquine – 4,7-dichloroquinoline (37.
In the next section 0.625 mg premarin amex, we will examine how certain types of pathophysiologic stimuli can provoke endothelial dysfunction discount premarin 0.625 mg with amex, and explore some of the consequences for the pathogenesis of vascular disease purchase 0.625 mg premarin. Since the heart has a limited and short-lived capacity for anaerobic metabolism buy discount premarin 0.625mg on line, its metabolic needs can be considered solely in terms of oxidative metabolism. The major determinants of myocardial oxygen demand include wall stress, contractile state, and heart rate. Systolic blood pressure is often used as an estimate for myocardial wall stress, and increases in blood pressure are associated with similar increases in wall stress. Contractility, which includes the velocity and magnitude of myocardial contraction, is the second major determinant of myocardial oxygen consumption. In the intact heart, sympathetic stimulation, and catecholamine or calcium administration can result in a substantial increase in myocardial oxygen consumption related to the increased contractility. Heart rate is the final important determinant of myocardial oxygen demand, and there is a direct relationship between heart rate and myocardial oxygen consumption. The role of heart rate is probably related to the increased number of contractions per minute, although increases in heart rate are associated with increased contractility as well. Schematic representation of the normal balance between myocardial oxygen demand and supply. One of the unique features of the coronary circulation is its high degree of oxygen extraction under basal conditions. Coronary sinus blood is typically only 20- 30% saturated, making it difficult for the heart to adjust to increasing metabolic needs by increasing oxygen extraction. Therefore, changes in myocardial oxygen consumption require changes in coronary flow which are similar in both direction and magnitude. The ability of the myocardium to regulate its flow according to its oxygen requirements is known as autoregulation, and coronary flow can increase 3-6 fold in response to increasing oxygen demand. In the absence of disease coronary blood flow is tightly coupled to changes in metabolic requirements of the myocardium. To understand factors modulating coronary flow, it is necessary to consider in some detail the relationship among coronary flow, driving pressure, and vascular resistance. Driving pressure is usually taken as the difference between arterial pressure and right atrial pressure, but the latter is low in the normal circulation, and the equation is often simplified to Q=Pa/R, where Pa = aortic pressure. Diagram of a transparent segment of myocardium illustrating the different components of resistance in the normal situation. Coronary vascular resistance (R) has been modeled to be the sum of three physiologic components which are illustrated in Figure 2. R1, or basal viscous resistance, originates in the large and medium-sized arteries and arterioles and relates to the cross- sectional area in these vessels. It is the minimum possible resistance of the system during diastole with the coronary bed fully dilated and is constant over long periods of time. R2, or autoregulatory resistance, is the major component of resistance and is thought to result from vascular smooth muscle tone in the arteriolar walls. Changes in its magnitude can occur in a single cardiac cycle in response to changes in myocardial metabolic requirements, with maximal vasodilatation occurring in as little as 15-20 seconds. R2 has traditionally been considered the primary mechanism which allows coronary flow to change in response to changing myocardial oxygen demand. R3 or compressive resistance, is due to compression of myocardial vessels and results from intramyocardial pressure. Compressive resistance varies during a single cardiac cycle and is especially large during systole. All three of these functional components of coronary vascular resistance can vary regionally, temporally, and transmurally, and this will be discussed subsequently. Figure 3 illustrates the effects of cyclical changes in R3 on overall flow and resistance in the coronary bed during a single cardiac cycle. Note that overall coronary resistance is 3-4 fold greater in systole than in diastole and results from increased compressive resistance (R3) during systole when intramyocardial forces are large. As a result, there is a marked difference in systolic and diastolic flow, and, in fact, only 15-20% of the total flow to the left ventricle occurs during systole. This is not the case for the less muscular right ventricle which receives a large proportion of its blood flow during systole as well as diastole (see Figure 4.
They have also been involved in pathological processes such as epilepsy and stroke cheap premarin 0.625mg visa. In addition to the anticipated agonist and competi- tive antagonist binding sites purchase 0.625mg premarin fast delivery, there are a number of other functional subsites on the receptor complex: glycine quality premarin 0.625mg, polyamine buy premarin 0.625 mg low price, Zn2+ and Mg2+. Each one of these additional bind- ing sites responds functionally to either endogenous or exogenous ligands and is thus also a reasonable target for drug design. Bioisosteric replacement of a carboxylate group also produces agonists; D,L-(tetrazol-5-yl)glycine (4. Likewise, with appropriate substitutions and replacement, glutamic acid analogs can also be competitive antagonists. In these antagonists, bioisosteric replacement of carboxylates with phosphonates is a frequent design strategy. Introduction of trans-4-methyl substituents into this piperidine derivative yields even greater receptor affinity. Work on glycine subsite antagonists is discussed in the section on glycine (section 4. Designing drugs to uniquely interfere with the biochemistry of a metallic anion in the central nervous system is non- trivial. It can be appreciated, from studies that attempt to design ion-specific chelating agents, that developing drugs to uniquely target one metal ion (e. Nevertheless, tricyclic antidepressants and phenoth- iazines, including desmethylimipramine and ethopropazine, have been suggested to act as zinc site ligands. The relationship between the zinc site and the magnesium site has also been considered. Oxytocin is used to induce labor in childbirth and to promote the expulsion of the pla- centa, although the antidiuretic activity of the native hormone is a disadvantage. Other drugs with uterotonic activity include the Ergot is from the fungus which infects cereals, mainly rye. A number of indole alkaloids have been isolated from this source, in which the indole moiety is lysergic acid. The peptide alkaloids have a slow and cumulative action, whereas the water-soluble ergonovine and its derivatives are fast acting. The latter is used to prevent postpartum hemorrhage by the compression of uterine blood vessels through uterine muscle contraction. Some of these alkaloids are -adrenergic blocking agents and have been used with moderate success in the treat- ment of migraine headaches. Diabetes insipidus (not to be confused with diabetes mellitus, which arises from a defi- ciency of insulin—frequently from pathology of the pancreas) is the disorder arising from a deficiency of vasopressin—frequently from pathology of the posterior pituitary. From a symptom perspective, both diabetes insipidus and mellitus are associated with polyuria (passing large amounts of urine) and polydypsia (drinking large amounts of fluid). The cyclobutyl homolog of oxilorphan, butorphanol (), is 4–10 times more active than morphine, has 50–70 times the activity of pentazocine as an analgesic, and 30 times the activity of pentazocine as an antagonist. In the benzomorphan series, cyclazocine and pentazocine are useful mixed agonist– antagonists. Unfortunately, the former has considerable hallucinogenic properties, although pentazocine is a very useful analgesic. Among the oripavines, buprenorphine () and diprenorphine () are valuable agonist–antagonists. The thyroid and parathyroid glands are two important endocrine organs that are heavily committed to the biosynthesis of hormones as chemical messengers. The thyroid gland, which surrounds the larynx, has an enormous variety of metabolic functions. The thiazolidinediones consist of troglitazone (), rosiglitazone (), and pioglitazone (). These agents work by enhancing target tissue insulin sensitivity by increasing glucose uptake and metabolism in muscle and adipose tissues. Thiazolidinediones are , which when used alone (“monotherapy”) can reduce glucose levels to the normal range without causing hypoglycemia.