By E. Masil. New World School of the Arts.
Which of the following consequences would you expect to occur in the liver after drinking two cups of strong expresso coffee? Assume that an increase in blood glucose concentration from 5 to 10 mM would result in insulin release by the pancreas discount 25mg meclizine amex. A mutation in pancreatic glucokinase can lead to MODY because of which of the following within the pancreatic -cell? Which one of the following organs has the highest demand for glucose as a fuel? Glucagon release does not alter muscle metabolism because of which of the following? The major carbohydrates in the American diet are starch quality meclizine 25 mg, lactose buy meclizine 25 mg overnight delivery, O O α1 buy generic meclizine 25 mg on-line,4 and sucrose. The starches amylose and amylopectin are polysaccharides com- OH OH n posed of hundreds to millions of glucosyl units linked together through -1,4 and Amylose -1,6 glycosidic bonds (Fig. Lactose is a disaccharide composed of glu- cose and galactose, linked together through a -1,4 glycosidic bond. Sucrose is a disaccharide composed of glucose and fructose, linked through an -1,2 glyco- CH OH CH OH sidic bond. The digestive processes convert all of these dietary carbohydrates to 2 2 O O their constituent monosaccharides by hydrolyzing glycosidic bonds between the sugars. O OH O OH The digestion of starch begins in the mouth (Fig. The salivary gland O α1,6 OH releases a-amylase, which converts starch to smaller polysaccharides called CH OH CH -dextrins. Salivary -amylase is inactivated by the acidity of the stomach (HCl). Pancreatic -amylase continues the digestion of -dextrins, converting them OH OH to disaccharides (maltose), trisaccharides (maltotriose), and oligosaccharides n called limit dextrins. Limit dextrins usually contain four to nine glucosyl residues Amylopectin and an isomaltose branch (two glucosyl residues attached through an -1,6 glycosidic bond). The digestion of the disaccharides lactose and sucrose, as well as further CH2OH CH2OH digestion of maltose, maltotriose and limit dextrins, occurs through disacchari- HO O O OH dases attached to the membrane surface of the brush border (microvilli) of intes- OH O OH tinal epithelial cells. The β1,4 sucrase–isomaltase complex hydrolyzes sucrose, most of maltose, and almost all OH OH of the isomaltose formed by glucoamylase from limit dextrins. Lactase- Galactose Glucose glycosylceramidase ( -glycosidase) hydrolyzes the -glycosidic bonds in lactose Lactose and glycolipids. A fourth disaccharidase complex, trehalase, hydrolyzes the bond (an -1,1 glycosidic bond) between two glucosyl units in the sugar trehalose. The monosaccharides produced by these hydrolases (glucose, fructose, and galactose) CH2OH are then transported into the intestinal epithelial cells. For disaccharides and greater, the sugars are linked through glycosidic bonds between the anomeric carbon of one sugar and O α1,2 HOCH a hydroxyl group on another sugar. The glycosidic bond may be either or , depending on 2 O its position above or below the plane of the sugar containing the anomeric carbon. A, to review terms used in the description of sugars). The starch amylose is OH CH OH a polysaccharide of glucose residues linked with -1,4 glycosidic bonds. Amylopectin is 2 HO amylase with the addition of -1,6 glycosidic branchpoints. Dietary sugars may be mono- saccharides (single sugar residues), disaccharides (two sugar residues), oligosaccharides Sucrose (several sugar residues) or polysaccharides (hundreds of sugar residues). One of the Sucrose salivarysalivary causes of lactose intolerance is a low level of αα–amylase–amylase lactase, which decreases after infancy in most of the world’s population (nonpersis- Sucrose tant lactase or adult hypolactasia).
Potential mechanisms whereby the cytoplasmic fumarate can be oxidized are presented in section III purchase meclizine 25 mg with visa. Amino acids that produce acetyl CoA or ketone bodies order meclizine 25mg on line. The amino acids synthesized from TCA cycle intermediates (aspartate meclizine 25mg, asparagines purchase meclizine 25mg on line, glutamate, glutamine, proline, and arginine) are reconverted to these intermediates during degradation. Histidine is converted to glutamate and then to the TCA cycle intermediate -ketoglutarate. Methionine, threonine, valine, and isoleucine form succinyl CoA, and pheny- lalanine (after conversion to tyrosine) forms fumarate. Because pyruvate and the TCA cycle intermediates can produce glucose in the liver, these amino acids are glucogenic. Some amino acids with carbons that produce glucose also contain other car- bons that produce ketone bodies. Tryptophan, isoleucine, and threonine produce acetyl CoA, and phenylalanine and tyrosine produce acetoacetate. These amino acids are both glucogenic and ketogenic. Two of the essential amino acids (lysine and leucine) are strictly ketogenic. They do not produce glucose, only acetoacetate and acetyl-CoA. CHAPTER 39 / SYNTHESIS AND DEGRADATION OF AMINO ACIDS 715 THE WAITING ROOM Piquet Yuria, a 4-month-old female infant, emigrated from the Soviet Union with her French mother and Russian father 1 month ago. She was normal at birth but in the last several weeks was less than normally attentive to her surroundings. Her psychomotor maturation seemed delayed, and a tremor of her extremities had recently appeared. When her mother found her hav- ing gross twitching movements in her crib, she brought the infant to the hospital emergency room. A pediatrician examined Piquet and immediately noted a musty odor to the baby’s wet diaper. A drop of her blood was obtained from a heel prick and used to perform a Guthrie bacterial inhibition assay using a special type of fil- ter paper. This screening procedure was positive for the presence of an excess of phenylalanine in Piquet’s blood. Homer Sistine, a 14-year-old boy, had a sudden grand mal seizure (with jerking movements of the torso and head) in his eighth grade classroom. The school physician noted mild weakness of the muscles of the left side of Homer’s face and of his left arm and leg. Homer was hospitalized with a tenta- tive diagnosis of a cerebrovascular accident involving the right cerebral hemisphere, which presumably triggered the seizure. Homer’s past medical history was normal, except for slight mental retardation requiring placement in a special education group. He also had a downward partial dislocation of the lenses of both eyes for which he had had a surgical procedure (a peripheral iridectomy). Homer’s left-sided neurologic deficits cleared spontaneously within 3 days, but a computerized axial tomogram (CAT) showed changes consistent with a small infarction (damaged area caused by a temporary or permanent loss of adequate arte- rial blood flow) in the right cerebral hemisphere. A neurologist noted that Homer had a slight waddling gait, which his mother said began several years earlier and was progressing with time. Further studies confirmed the presence of decreased mineralization (decreased calcification) of the skeleton (called osteopenia if mild and osteoporosis if more severe) and high methionine and homocysteine but low cystine levels in the blood. All of this information, plus the increased length of the long bones of Homer’s extremities and a slight curvature of his spine (scoliosis), caused his physician to suspect that Homer might have an inborn error of metabolism.
Taking a cue from that experience generic meclizine 25 mg mastercard, our group was the ﬁrst to apply such methodology to the ﬁeld of neuroepidemiology (21–24) trusted 25 mg meclizine. In our study of occupational metal exposures and PD (21) effective 25 mg meclizine, a case- blind industrial hygienist assessed metal exposure in all jobs held for 6 months or longer for all subjects throughout adult life generic meclizine 25 mg overnight delivery. The hygienist considered subjects’ tasks involving speciﬁc metals, the tools used, the ambient environment, and measures taken for protection from exposure. In a parallel methodological study (22), we compared assessment by self- report, job titles linked to a job exposure matrix (JEM) (25), and assignment by an industrial hygienist. Data derived from self-report and a JEM separately, as well as information from both methods, were not comparable with industrial hygienist assessment. Taking industrial hygienist exposure assessment as the gold standard, we showed that the method of exposure assessment can have a large inﬂuence on the association between a disease outcome and exposure. This was further highlighted in a recent reanalysis (J. We found that, if we had relied on self-report alone instead of an industrial hygienist’s case-blind rating of factors associated with exposure, no Copyright 2003 by Marcel Dekker, Inc. Moreover, had we only assessed ever-exposure to metals instead of also evaluating chronic exposure, no signiﬁcant ﬁndings would have been seen. As opposed to self-report, our expert assessment methodology was very amenable to evaluating exposure duration, which, in hindsight, was critical in teasing apart the PD- occupational metal exposure association. Despite what appears to be an advantage of expert assessment of metal exposures, similarly trained industrial hygienists can reach different conclusions in reviews of the same data set (19,23,26,27). This issue of subjectivity suggests that it is difﬁcult to reliably transform an occupational history into an estimate of exposure, and implies that it may be desirable to combine such assessments with a more objective measure of chronic exposure to metals, if this is available. Wherever possible, it would seem desirable to compare such data with exposure measurements (e. As an extension of our experience with retrospective metal exposure assessment, we suggest that employing industrial hygienists or occupational toxicologists with expertise in other ﬁelds (e. Resulting exposure assignments should be compared with speciﬁc records of relevant exposures at the time at risk, if available. Finally, it may be helpful to construct a cumulative lifetime exposure history to a toxicant of interest in order to best assess its dose effect on disease outcome. Occupational Metal Exposure Metals may be involved in the etiology and/or pathogenesis of PD. For example, manganese (28), copper (29), lead (28), and iron (30) have been shown to promote oxidative stress by free radical generation, an ongoing 3þ process in the PD substantia nigra (SN) (30). Iron (as Fe and total levels) has been reported to be elevated in the PD SN (31), but copper has either been reported to be increased (32) or decreased (33,34). Manganese may have a role in catecholamine autoxidation (35), in the formation of neuromelanin (36), and, perhaps, in the production of Lewy bodies (37). Copper(II) can react with ascorbate (38) or levodopa (39) to produce genotoxic free radicals. Lead(II) may be directly genotoxic, as it inhibits DNA polymerase (40), possibly hampering DNA repair. This potential Copyright 2003 by Marcel Dekker, Inc. The relationship between occupational exposure to speciﬁc metals and PD has been examined infrequently in case-control studies with sizable populations (21,42–46). Results in these studies have varied, likely because of differences involving the means of exposure assessment, the duration of exposure, as well as the populations studied. Occupational Exposure to Selected Metals and PD Manganese. Finally, when considering manganese exposure as a risk factor for PD, it is important not to reject a potential association because of confusion with the severe poisoning seen in manganism, in which there is preferential affection of the globus pallidus rather than the SN, with clinical dystonic parkinsonism produced most often (44,45). Ohlson and Hogstedt (46), in a hospital-based case-control study in Sweden, found no group difference in occupational exposure to mercury, assessed by self-report. However, Ngim and Devathasan (47), in a hospital-based case-control study in Singapore, found a signiﬁcant association between mercury exposure and PD, assessed by self-report. They also found a dose-response relationship when comparing blood mercury levels from the highest tertile (OR ¼ 9.
These results are more specifically a demonstration that the muscles have severe decreased excursion and unless the active range is perfectly placed proven meclizine 25 mg, they are likely to be perceived as weak- ness 25mg meclizine for sale. Over time cheap 25mg meclizine mastercard, there is a tendency for the finger flexion contracture to recur buy meclizine 25 mg free shipping, but seldom to the level it was before surgery. Other Treatment Several other methods of lengthening are possible including flexor prona- tor slide (proximal lengthening), Z-lengthening of individual flexor tendons, selective peripheral motor neurectomy,39 and sublimus to profundus trans- fer. The flexor pronator slide provides little control and excessive weakness for children with any function; for those who are severely involved, the Z- lengthening is an easier and simpler operation. Another option similar to the slide is excision of the proximal muscle fascia with detaching the muscle from the bone. With the limited con- trol present in spastic hands, individual tendon Z-lengthening is more com- plicated and provides little gain. Transfers of flexor digitorum superficialis to flexor digitorum profundus to create a single motor unit for the fingers seem to also provide little benefit over simpler lengthening procedures. Most of the function of a hemiplegic hand is for gross finger grasp and thumb key pinch, both ac- tivities requiring power more than fine control. Complications of Treatment The major complication is overlengthening, leaving the fingers with no power in the range where individuals need power for function. This loss of function usually recovers over several years, but only partially. We have not had any individuals with such severe weakness that they desired an operative attempt to correct the overlengthening. Some individuals want ad- ditional lengthening if there is still too much flexion. Those who want addi- tional lengthening are mainly individuals in whom a decision was initially made that the finger flexors need lengthening but no or very minimal length- ening was performed. The other complication is leaving an imbalance with an excessively strong flexor digitorum profundus and extensor digitorum longus causing the swan neck deformity to develop. This deformity can be extremely dis- abling because it locks the fingers so that they cannot be used. Treatment indicated is described in the next section. Finger Swan Neck Tightening of the finger flexors secondary to the wrist flexion deformity plus spasticity of the intrinsic muscles and the extensor digitorum longus results in hyperextension of the proximal interphalangeal joint and flexion of the distal interphalangeal joint, which causes the swan neck deformity. The volar cap- sule of the proximal interphalangeal joint becomes stretched out secondarily. When the deformity is severe, the fingers may become locked into extension and cannot actively flex (Figure 8. This deformity can be the result of over- lengthening the flexor digitorum superficialis in the face of a spastic and co- contracting flexor digitorum profundus and extensor digitorum longus. Treatment The initial treatment should include the use of the figure-of-eight finger or- thotic, which prevents extension of the proximal interphalangeal joint (Fig- ure 8. This splint can be made from plastic and, if tolerated by the patients, cosmetically appealing metal splints, which look like finger rings, can be ordered. If the hyperextension is forceful, many individuals find the rings uncomfortable because of the small area of skin contact, which causes high local skin pressure. For supple and moderate deformities that can easily be passively cor- rected, correction of the swan neck deformity as well as the wrist flexion de- formity should be done at the same time. Two procedures, a volar capsu- lodesis and a flexor superficialis tenodesis, have been described to correct the deformity. Midlateral or Z-plasty incisions can be performed to expose the flexor surface of the prox- imal interphalangeal joint. The volar capsule is detached and advanced proximally on the distal end of the proximal phalange. One half of the flexor digitorum superficialis is detached proximally and sutured to the tendon sheath proximally.