Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hemodynamic effects of long-term (3 months) treatment with enalapril, a potent angiotensin converting enzyme inhibitor, were studied in 12 randomly selected patients with portal hypertension and a previous episode of hemorrhage from esophageal varices. All these patients underwent injection sclerotherapy of varices at 1-week intervals. As a control group 13 patients treated only with injection sclerotherapy and placebo were used. After 3 months the wedged hepatic venous pressure (25.5 +/- 4.8 vs. 21.3 +/- 4.8 mmHg) and the non-wedged hepatic venous pressure gradient (17.0 +/- 6.0 vs. 12.6 +/- 3.4 mmHg) were significantly lower than the basal values (p < 0.01) in the group treated with enalapril. A large decrease (> 3 mmHg) in these pressures was observed only in 50% of the patients. In the group treated with sclerotherapy+placebo this pressure reduction was not observed. Systemic hemodynamics and liver function tests did not change during the treatment. None of our patients died during the study or the next 6 months. We conclude that enalapril lowers portal pressure in patients with portal hypertension, although not in all of them, and may be used to good effect to manage patients with esophageal varices in combination with sclerotherapy.
 ...
PMID:Effect of enalapril treatment and sclerotherapy of esophageal varices on hepatic hemodynamics in portal hypertension. 133 75

Endothelial cells can be harvested from segments of adult human saphenous vein in a varicose condition removed from patients having single or bilateral vein ligation and stripping. The cells are harvested by scraping with a scalpel, seeded on to gelatin coated or Primaria flasks and are passaged by removal with a rubber policeman. The cells cultured in this manner are maintained in a growth medium that is not supplemented with growth factors. The cells grow with a cobblestone monolayer morphology, possess angiotensin converting enzyme activity and react with antibodies to Factor VIII antigen. The cells fluoresce brightly after reaction with monoclonal antibodies specific for human endothelial cells. Thus, stripped varicose vein segments provide a readily available source of endothelial cells.
 ...
PMID:Varicose veins as a source of adult human endothelial cells. 299 69

The objective of pharmacotherapy of portal hypertension is to reduce the portal pressure and the subsequent reduction of pressure and blood flow in the oesophageal varicosities in patients with portal hypertension. Pharmacological treatment is used in acute bleeding from oesophageal varices where it is a very useful first step for arresting haemorrhage and it does not require any special training or complicated equipment. Pharmacotherapy holds its place also in primary and secondary prophylaxis of oesophageal variceal bleeding. In particular a combination of pharmacotherapy with sclerotherapy is useful to reduce the occurrence of early recurrent bleeding. Among hitherto known vasoactive drugs the following ones are used most frequently: vasopressin, terlipressin, somatostatin, beta-blockers, nitrates and ACE inhibitors. Other drugs influencing portal haemodynamics are the subject of research.
 ...
PMID:[Pharmacologic treatment of portal hypertension]. 897 62

A posthepatitic cirrhotic patient may undergo elective or urgent abdominal operation for an extra-hepatic or hepatic disease. According to the high postoperative morbidity (61%), surgery is indicated only for symptomatic or complicated cholelithiasis. A surgical procedure for refractory ascites has been devised to create a permanent peritoneo-venous shunt by a one way pressure-sensitive valve (Leveen). The procedure is simple and brings a long lasting relief with recovery in strength and nutrition and improved kidney function. Sclerotherapy is widely used to treat acute variceal bleeding while repeated sclerotherapy is used in the long-term management to eradicate varices. When indicated, liver transplantation is the best treatment to prevent variceal bleeding recurrence. Also portosystemic shunts effectively prevent recurrent variceal bleeding. They are, however, major operations with an important morbidity and mortality, particularly in poor risk patients. The most advocated shunts today are the Warren distal splenorenal shunt and the Sarfeh portacaval shunt using a small diameter prosthetic H-graft. The transjugular intrahepatic portosystemic stent-shunt (TIPSS) is a new treatment for portal hypertension and its complications. From a haemodynamic point of view it allows balanced hepatic perfusion. Postoperative mortality is rare; further bleeding and encephalopathy are reasonably acceptable. The most relevant complications concern dislocation of the prosthesis, stenosis and thrombosis of the shunt, which can be corrected by non-invasive dilatation. Encephalopathy is the main complication of surgical portosystemic shunts. It is usually controlled by protein diet restriction, and administration of lactulose or oral antibiotics. In severe forms the patients may be treated by an oesophageal transection with oesophagogastric devascularization, and by a postoperative suppression of the portosystemic shunt using external maneuvers. Posthepatitic liver cirrhosis is frequently complicated by the onset of an hepatocellular carcinoma. Early detection (aFP, DCP, Echography) and curative resection are the best ways to improve long term prognosis. Segmentectomy achieves a good balance between liver function preservation and radical exeresis for tumours less than 5 cm in diameter. Liver transplantation may be considered for the treatment of long-staging cirrhotic patients in whom hepatocarcinoma development has been recognized at an early presymptomatic stage. Hepatic arterial chemoembolization (gelfoam, lipiodol, mitomycin C or doxorubicin) may improve the survival of patients with unresectable malignant disease of the liver. A marked reduction in liver size may occur in the weeks following an effective chemoembolization with objective (CT scan) and subjective improvement (amelioration of specific symptoms). Liver chemoembolization is absolutely contraindicated in the presence of jaundice disordered liver function (Child C) or complete portal venous obstruction. In the last years, the number of patients treated by liver transplantation has greatly increased. Surgical technique, postoperative management, and immunosuppressive therapy account for the dramatic improvement of the results. However, indications for selection of patients and the timing for liver transplantation are still not well defined.
 ...
PMID:[Surgical approach to posthepatitic cirrhotic patient today]. 927 83

Circadian rhythms have been shown both in the expression of the period (per) gene in 'lateral neurons' and in cells of the outermost neuropil, or lamina, of the fly's optic lobe. Some lateral neurons also exhibit PDH peptide-like immunoreactivity, arborizing widely throughout the optic lobe. Using confocal microscopy in the housefly, we analysed the size and spacing of PDH neurite varicosities, sites of possible peptide release exhibiting circadian rhythmicity. During the subjective day in constant darkness, there were fewer, larger varicosities than during subjective night. The endogenous rhythm was masked by the light exposure that occurred under a day-night cycle and continuous light conditions. Our findings indicate that PDH neurites convey circadian information out from the pacemaker, where they could regulate the circadian rhythms that have been described in the lamina, possibly via cyclical release of their peptide.
 ...
PMID:Neurites of period-expressing PDH cells in the fly's optic lobe exhibit circadian oscillations in morphology. 928 34

The therapy of portal hypertension depends to a significant extent on its clinical manifestation. In cases of acute haemorrhage from oesophageal varices in patients with portal hypertension, the objective of the therapy is to stop the haemorrhage (endoscopically, or by compression by means of a balloon probe) and to decrease the pressure and the reflux within the portal vascular bed. Urgent sclerotisation under the simultanous pharmacologic decrease of portal hypertension is successful in 93-95%. There is an alternative procedure residing in introducing a balloon probe for several hours and subsequent repeated sclerotisation until a complete eradication of varices is achieved regarding the prevention of haemorrhage exacerbation. Urgent surgical solution is on the basis of the results of various investigated studies reserved for patients in whom endoscopic sclerotisation was not successful. Indication of surgical therapy must be also deliberated in candidates for liver transplantation, regarding the possible consequent technical problems after some types of interventions. Endoscopic sclerotisation of oesophageal varices is also an appropriate preparation for transplantation of the liver in patients with liver cirrhosis included into the transplantation programme. TIPS is a perspective new method in the therapy of portal hypertension of both, non-bleeding varices, as well as in other indications. It is also a certain intermediating link in therapy in some patients with liver cirrhosis on the waiting list of candidates for liver transplantation. Pharmacotherapy is a significant part of the portal hypertension therapy. It is appropriate to combine the endoscopic treatment with pharmacotherapy of portal hypertension in both, cases of acute haemorrhage, as well as in the prevention of haemorrhage exacerbation. In cases of acute haemorrhage, the combination of glypressin with nitroglycerin is justified, as well as the therapy by somatostatin. The prevention of haemorrhage exacerbations uses a whole series of vasoactive substances, especially nitrates, beta-blockers and ACE inhibitors. The prevention of the first bleeding includes the prophylactic therapy (endoscopic, pharmacologic, or surgical) recommended only in a selected group of patients under high risk of bleeding. The possible perspective option will reside especially in the combined pharmacological therapy, the fact of which will have to be proven in the future. (Fig. 1, Ref. 25.)
 ...
PMID:[Treatment of portal hypertension]. 958 83

The visual system of the fly's compound eye undergoes a number of cyclical day/night changes that have a circadian basis. Such responses are seen in the synaptic terminals of the photoreceptors and in their large monopolar-cell interneurons in the first optic neuropile, or lamina. These changes include, in the photoreceptor terminals, rhythms in the numbers of synapses and the vertical migration of screening pigment; and, in the monopolar cells L1 and L2, a rhythm in the transients of the electroretinogram and in the cyclical swelling of L1 and L2 lamina axons, as well as of the epithelial glia that surround these. Some of these changes are seen in both the housefly and the fruit fly, but the time-course of such changes differs between the two species. Many of the changes are influenced by the injection of various transmitter candidates, in a direction that can be reconciled with the possibility of normal endogenous release of two substances, 5HT from the neurites of 5HT-immunoreactive neurons, and pigment dispersing factor peptide from the neurites of PDH cells. Consistent with this interpretation, the immunoreactive varicosities of PDH cells exhibit size changes attributable to their cyclical release of peptide, or to its cyclical synthesis and/or transport from the PDH cell somata. Thus, neurotransmitter substances not only have rapid electrophysiological actions in the optic lobe, but also longer-lasting, presumably indirect, neuromodulatory actions, which are manifest as structural changes among the lamina's neurons and synapses. These actions involve an interplay between aminergic and peptidergic systems, but the exact role and especially the site of action of each has still to be elucidated.
 ...
PMID:Neurotransmitter regulation of circadian structural changes in the fly's visual system. 1033 27

Neurones immunoreactive to an antibody against a pigment-dispersing hormone (PDH-ir) are considered to be pacemaker cells in the neuronal circadian system of flies. We investigated the ultrastructure of PDH-ir varicosities, possible releasing sites of the PDH-like peptide, in the distal medulla of the optic lobe and in the dorsal protocerebrum of the two fly species Drosophila melanogaster and Musca domestica. In both species PDH-ir varicosities show accumulation of dense core vesicles (DCVs). PDH-like peptide is localized in the DCVs as shown by post-embedding immuno-electron microscopy. Localization of PDH-like peptide in DCVs and normally lacking synaptic specializations at PDH-ir varicosities in the medulla are interpreted as a non-synaptic paracrine release of peptide.
 ...
PMID:Ultrastructural characteristics of circadian pacemaker neurones, immunoreactive to an antibody against a pigment-dispersing hormone in the fly's brain. 1515

A 13-year-old boy, known case renal stone disease came with the complaints of abdominal pain along with low grade fever. On examination, hepatosplenomegaly was noted while his lab reports showed a low hemoglobulin with a raised ESR. His blood and urine cultures showed no growth. Viral markers, autoimmune profile, C and p ANCA were all negative apart from a raised serum IgG level. Ultrasound abdomen showed a hyperechoic liver with an enlarged spleen along with splenic varices and minimum ascites. Ultrasound hepatic doppler was normal. Serum AFP levels were normal while workup for Wilson's disease was negative. Fibroscan showed F4 fibosis. CT scan abdomen showed an enlarged left lobe of the liver along with an enlarged spleen. His EGD revealed varices. So liver biopsy was done that was suggestive of chronic granulomatous disease with ZN stain testing negative for TB.PPD, urine for AFB were both negative. Serum ACE levels were raised. He started ATT therapy but his condition did not improve. So, on the suspicion of hepatic sarcoidosis, he started on steroids and had a drastic improvement in his condition.
 ...
PMID:Hepatic Sarcodosis presenting as portal hypertension in a young boy. 2956 70

Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin II type receptor 1 blockers, which target the components of the classical renin angiotensin system (RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant off-target effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective -blockers (NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these drugs. Although statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This review outlines the mechanisms related to the pathogenesis of portal hypertension and attempts to provide an update on currently available therapeutic approaches in the management of portal hypertension with special emphasis on how the alternate RAS could be manipulated in our search for development of safe, specific and effective novel therapies to treat portal hypertension in cirrhosis.
 ...
PMID:Cirrhotic portal hypertension: From pathophysiology to novel therapeutics. 3317 89


1