Zebeta

By F. Mitch. Stevens-Henager College.

Compared with the glu- the pathways of steroid biosynthesis in the adrenal cortex zebeta 10mg visa. Because of similarities in their structures, the glucocorti- Adrenal Steroid Hormones Are Synthesized coids and aldosterone have overlapping actions. For exam- From Cholesterol Cholesterol is the starting material for the synthesis of steroid hormones. A cholesterol molecule consists of four The Average Daily Production of Hor- interconnected rings of carbon atoms and a side chain of TABLE 34. In all, there are 27 carbon atoms in cholesterol, numbered as Hormone Amount Produced (mg/day) shown in the figure. The cho- 610 PART IX ENDOCRINE PHYSIOLOGY 21 22 24 26 20 23 25 Blood 18 Apoprotein 12 17 LDL 11 27 19 16 Coated pit Plasma membrane 13 1 9 C D 2 15 14 10 8 A B Endocytosis 3 5 7 4 6 OH Cholesterol ester OH CEH Fatty acid cholesterol Steroids ACAT CEH Cholesterol ester HMG CoA reductase O Acetate Lipid HO droplet O Adrenal cortical cell FIGURE 34. Most choles- terol comes from low-density lipoprotein (LDL) particles in the blood, which bind to receptors in the plasma membrane and are The formation of pregnenolone from cho- taken up by endocytosis. The hydrogen atoms on the car- acyltransferase; HMG, 3-hydroxy-3-methylglutaryl. The endo- of cholesterol esters, single molecules of cholesterol ester- cytic vesicle containing the LDL particles fuses with a lyso- ified to single fatty acid molecules. The cholesterol esters in used in steroid biosynthesis is generated from these choles- the core of the particle are hydrolyzed to free cholesterol terol esters by the action of cholesterol esterase (choles- and fatty acid by the action of CEH. The free cholesterol generated by that cleavage en- verted again to cholesterol esters by the action of the en- ters mitochondria located in close proximity to the lipid zyme acyl-CoA:cholesterol acyltransferase (ACAT). The process of remodeling the cholesterol mole- esters are then stored in the lipid droplets of the cell to be cule into steroid hormones is then initiated. The cholesterol that has been removed from the lipid When steroid biosynthesis is proceeding at a high rate, droplets for steroid hormone biosynthesis is replenished in cholesterol delivered to the adrenal cell may be diverted di- two ways (Fig. Most of the cholesterol converted to rectly to mitochondria for steroid production rather than steroid hormones by the human adrenal gland comes from reesterified and stored. Accumulating evidence suggests cholesterol esters contained in low-density lipoprotein that high-density lipoprotein (HDL) cholesterol may also (LDL) particles circulating in the blood. A 400-kDa protein mol- from acetate by the adrenal glands is a significant but minor ecule called apoprotein B100 is also present on the surface source of cholesterol for steroid hormone formation.

There is evidence from some experimental studies that metENK can decrease GABA release in the GPext while dynorphin reduces GLUT release in GPint discount zebeta 10mg line. The former effect would reduce the inhibition of GPext neurons by the Ind Path (just as DA would in the striatum) leaving them with greater control of the SThN and hence reduced stimulation of GPint. Dynorphin inhibition of glutamate release within GPint would have the same effect (Fig. Since the increased output of this nucleus is believed to cause akinesia these processes could be of benefit in PD. Preliminary data indicate that in the reserpinised rat or MPTP marmoset, the enkephalin agonist (SNC80) reduces PD-like symptoms without causing increased activity, i. Enadoline, a dynorphin-like kappa opioid agonist also has similar effects in the same models. Despite the fact that neither delta nor kappa agonists caused hyperkinetic (dyskinesia-like) activity in the above studies, antagonism of these receptors with naloxone can apparently diminish such activity induced in animals by long-term dosage with levodopa and has been shown to work in preliminary human studies (Henry and Brotchie 1996). Of course, levodopa-produced DA might be expected to inhibit striatal GABA/ENK output to GPext sufficiently to ensure that very little met ENK was actually released to be antagonised, although dynorphin release from the Dir Path could be maintained so that blocking its inhibitory effects on glutamate release would result in decreased output from GPint and a shift away from dyskinesia. Clearly many more data are needed on the release of these peptides and their function in GP before their possible role in PD can be properly evaluated but they illustrate an interesting alternative approach to therapy. Enkephalin released from axon terminals of neurons of the indirect pathway (see Fig. This will free the neurons to inhibit the subthalamic nucleus (SThN) and its drive to GPint and SNr which in turn will have less inhibitory effect on cortico-thalamic traffic and possibly reduce akinesia. Dynorphin released from terminals of neurons of the direct pathway may also reduce glutamate release and excitation in the internal globus pallidus and further depress its inhibition of the cortico-thalamic pathway. High concentrations of these peptides may, however, result in dyskinesias. Currently benzhexol and benztropine are sometimes added to levodopa therapy but peripheral effects such as dry mouth, blurred vision and constipation are unpleasant. They are also often used to counteract neuroleptic-induced extrapyramidal effects. Stratal GABA (ENK) neurons are normally inhibited by both DA, released from nigrostriatal nerve terminals and GABA from their recurrent collaterals.

As mentioned earlier best zebeta 10mg, the hepatic sinusoid is Hepatocyte extremely porous and allows the rapid exchange of materi- Perisinusoidal space als between the perisinusoidal space and the sinusoid. The sinusoids empty into the central veins, which subsequently join to form the hepatic vein, which then joins the inferior Kupffer cell vena cava. Hepatic blood flow varies with activity, increasing af- Sinusoid ter eating and decreasing during sleep. Blood flow to the intestines and spleen and, in turn, in the portal vein is predominantly regulated by the splanchnic arterioles. In Sinusoidal this way, eating results in increased blood flow to the in- endothelial cells testines followed by increased liver blood flow. Portal hy- pertension is the most common complication of chronic liver disease and accounts for a large percentage of the finger-like projections that extend into the perisinusoidal morbidity and mortality associated with chronic liver space, greatly increasing the surface area over which hepa- diseases (see Clinical Focus Box 28. Endothelial cells of the liver, unlike those in other parts of the cardiovascular system, lack a basement membrane. The Liver Has an Important Lymphatic System Furthermore, they have sieve-like plates that permit the ready exchange of materials between the perisinusoidal The hepatic lymphatic system is present in three main ar- space and the sinusoid. Electron microscopy has demon- eas: adjacent to the central veins, adjacent to the portal strated that even particles as big as chylomicrons (80 to 500 veins, and coursing along the hepatic artery. Al- gans, it is through these channels that fluid and proteins are though the barrier between the perisinusoidal space and drained. The protein concentration is highest in lymph the sinusoid is permeable, it does have some sieving prop- from the liver. For example, the protein concentration of hepatic In the liver, the largest space drained by the lymphatic lymph, assumed to derive from the perisinusoidal space, is system is the perisinusoidal space. These are cites, the accumulation of serous fluid in the peritoneal cav- resident macrophages of the fixed monocyte-macrophage ity. Ascites is another common cause of morbidity in system that play an extremely important role in removing patients with chronic liver disease.

The ab- syncytium because the excitation of one cardiac cell even- tually leads to the excitation of all cells trusted zebeta 5 mg. The cellular basis sence of a well-defined plateau occurs because K channels for the functional syncytium is low-resistance areas of the open and pull the membrane potential toward the K equi- librium potential. Gap junctions but the rate of depolarization during phase 4 is much slower between adjacent cells allow small ions to move freely from than that of the nodal cells. In the normal heart, phase 4 of one cell to the next, meaning that action potentials can be Purkinje fibers is usually thought to be a stable resting propagated from cell to cell, similar to the way an action membrane potential. The Refractory Period Is Caused by a Delay Excitation Starts in the SA Node Because in the Reactivation of Na Channels SA Cells Reach Threshold First As discussed in Chapter 10, cardiac muscle cells display Excitation of the heart normally begins in the SA node be- long refractory periods and, as a result, cannot be cause the pacemaker potential of this tissue (see Fig. A prolonged re- reaches threshold before the pacemaker potential of the AV fractory period eliminates the possibility that a sustained node. The pacemaker rate of the SA node is normally 60 to contraction might occur and prevent the cyclic contrac- 100 beats/min versus 40 to 55 beats/min for the AV node. The refractory period be- Pacemaker activity in the bundle of His and the Purkinje gins with depolarization and continues until nearly the system is even slower, at 25 to 40 beats/min. This occurs because the and ventricular cells do not exhibit pacemaker activity. Many cells of the SA node reach threshold and depolar- Na channels that open to cause phase 0 close and are in- active until the membrane repolarizes. This leads to depolarization of the neighboring the relatively smaller current brings neighboring cells to right atrial cells and a wave of depolarization begins to threshold more slowly, decreasing the rate at which elec- spread over the right and left atria. Other significant factors are the slow upstroke of the action potential because it depends on 2 slow voltage-gated Ca channels and, possibly, weak elec- The Action Potential Is Propagated by Local trical coupling as a result of relatively few gap junctions. Currents Created During Depolarization Propagation of the action potential through the AV node takes approximately 120 msec. Excitation then proceeds As Na ions enter a cell during phase 0, their positive through the AV bundle (bundle of His), the left and right charge repels intracellular K ions into nearby areas where depolarization has not yet occurred. Inflammation, hypoxia, vagus nerve activity, and cer- The local buildup of K depolarizes adjacent areas until threshold is reached.