Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 30-year-old man had an acute onset of orthostatic lightheadedness, sweating disturbance, paroxysmal cough and loss of potency. These symptoms reached the peak in two weeks, and then remitted very slowly. He was admitted to our hospital for further evaluation when he was 39 years old. Neurological examinations revealed right Horner's syndrome, dry skin and impotence, but neither motor nor sensory system was impaired. No abnormalities were found on routine examinations of the blood and cerebrospinal fluid, motor and sensory nerve velocities, computed tomography and electroencephalography. On sural nerve biopsy, the density of unmyelinated fibers was mildly decreased (13,857/mm2), whereas that of myelinated fibers was normal (7,220/mm2). Autonomic function tests disclosed orthostatic hypotension (-31 mmHg) on tilting, reduced levels of serum noradrenaline and vanillyl mandelic acid, supersensitive responses to noradrenaline infusion and adrenaline eye-dripping, severe sweating impairment and complete absence of sympathetic skin response. On the other hand, Aschner's test, Czermak's test and coefficient variation of R-R intervals were all normal. These results suggested that the chief lesion was located in the postganglionic fiber of sympathetic efferent pathway. We (Hayashi et al, 1990) quantified acetylcholinesterase (AchE)-positive fibers in the specimens of sural nerve biopsy, and reported that the density of AchE-positive fibers was correlated to the function of sympathetic postganglionic fibers. The density of AchE-positive fibers in the present case of acute idiopathic pandysautonomia (AIPD) was severely decreased to 225/mm2 by optical microscopy (control: 5,703 +/- 1,289/mm2), and to 2,996/mm2 by electron microscopy (control: 14,112 +/- 3,987/mm2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of acute idiopathic pandysautonomia--a histochemical study of sural nerve by acetylcholinesterase staining]. 137 6

Penile tissue (consisting of corpus cavernosum and tunica albuginea) was obtained from 19 patients undergoing surgery for the implantation of penile prostheses. The tissue was examined for vasoactive intestinal polypeptide-like immunoreactivity in nerves, acetylcholinesterase-positive staining in nerves and noradrenaline content. Impotence was due to a variety of causes; 11 patients were classified as a 'non-neuropathic' group on the basis of their clinical history which included Peyronie's disease, vascular disease, hypertension and psychogenic impotence. Vasoactive intestinal polypeptide-like immunoreactive and acetylcholinesterase-positive nerves were present and the pattern and distribution were similar in each patient in this group. The noradrenaline content of the tunica albuginea was significantly lower than the corpus cavernosum (p less than 0.02), although there was a linear relationship between the noradrenaline contents of the two regions (r = 0.95, p less than 0.01). By comparison, a complete absence of vasoactive intestinal polypeptide-like immunoreactivity in nerves was observed in a patient with a cauda equina lesion. Five out of six diabetic patients studied revealed a marked reduction in vasoactive intestinal polypeptide-like immunoreactivity in nerves associated with the cavernous smooth muscle, while acetylcholinesterase-positive staining was reduced in three out of five diabetic patients studied. The noradrenaline content of the corpus cavernosum from diabetic patients was significantly lower (p less than 0.02) than that of the 'non-neuropathic' group. The noradrenaline content of the tunica albuginea, however, was similar in both groups. The results provide evidence that VIPergic, cholinergic and adrenergic nerves in the penis are affected in diabetes mellitus and thus may contribute to the development of impotence in diabetic patients.
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PMID:Changes in the VIPergic, cholinergic and adrenergic innervation of human penile tissue in diabetic and non-diabetic impotent males. 243 29

In the United States, the drugs most commonly used to treat peptic ulcer disease are antacids and the H2-receptor antagonists cimetidine and ranitidine. Other available agents include anticholinergics and the coating agent sucralfate. Investigational drugs such as colloidal bismuth, carbenoxolone, prostaglandins, the tricyclic compound pirenzepine, and substituted benzimidazoles are not available for use in the United States. Most of the commercially available and investigational compounds have similar efficacy; therefore the optimal drug may be the one associated with the fewest adverse effects and the most convenient dosing regimen. Cimetidine causes a small number of adverse effects, including neuropsychiatric disorders, gynecomastia, impotence, loss of libido, elevation of serum creatinine and serum transaminases concentrations, and drug interactions. Some of these reactions have been of clinical significance. Presently, there are rare reports of gynecomastia, bradycardia, inhibition of acetylcholinesterase, headache, lethargy, diarrhea, and rash in patients receiving ranitidine. Antacids can produce either diarrhea or constipation and have been associated with low serum phosphorus concentrations, and metabolic alkalosis. Anticholinergics, especially in elderly or debilitated patients, can cause central nervous system disorders, intestinal atony, or urinary retention. Sucralfate may cause constipation, diarrhea, nausea, and headache. The investigational agents have their own side effect profiles. The adverse effects of anticholinergics make them unattractive therapeutic choices, and antacids and sucralfate have inconvenient dosing requirements compared with some equally efficacious alternatives. In addition, clinical experience with sucralfate in the United States is limited. The safety record of cimetidine is admirable. As clinical experience with ranitidine increases, currently unrecognized adverse effects may be reported. However, based on current data, ranitidine is as effective as cimetidine and is associated with a lower incidence of side effects.
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PMID:Problems associated with medical treatment of peptic ulcer disease. 609 62

As clinicians we talk about "the best interests of our patients". How can a treatment which doubles the rate of cognitive decline, triples the rate of stroke, doubles mortality, substantially increases falls and fractures and reduces quality of life be beneficial, especially, as in real life, once neuroleptics are started they are rarely discontinued with cumulative adverse effects? As there is clearly no rational reason for prescribing, we need to consider other explanations. We would suggest the following: Therapeutic impotence: Doctors, especially specialists feel they need to do something, and prescribing a familiar drug is the easiest option. Ignorance: Doctors are either unaware of the substantial evidence of harm with neuroleptics or are swayed by slick marketing information, portraying atypical neuroleptics in an "over-safe" light that does not reflect the actual data. Placebo effect: If neuroleptics are prescribed, the majority of patients experience an improvement in BPSD symptoms. This reinforces the apparent value of this practice, as we like to take the credit for any improvements that occur. The reality is that the majority of people would have experienced a comparable improvement with monitoring. Bowing to pressure: Sometimes the pressure to respond can be great, and a prescription is an easy way to relieve the pressure. This is understandable, and reflects a similar phenomenon to that of general practioners prescribing antibiotics for sore throats. In neither situation does it represent good practice. Lack of skills to implement non-pharmacological alternatives: The main evidence for alternative treatment options are for therapies that by and large are not a core part of the physician or psychiatrist's skill-base, such as psychological interventions. Doctors therefore feel uncomfortable pursuing these options. Why for example is so little time spent on the nonpharmacological interventions that everyone agrees should be the first line of treatment for BPSD in people with dementia? It is largely assumed that the "enlightened clinician has already appropriately assessed and diagnosed the patient and exhausted all the possible environmental and behavioral interventions before resorting to the prescription pad." Accumulating evidence clearly indicates that the need for psychotropic medication is substantially reduced by proactive services or interventions which can provide training and promote psychological, social and environmental and sensory interventions. The prescription but is an easy but not an acceptable alternative. Over-adherence to prescribing guidance: There are pharmacological alternatives to neuroleptics if a prescription is needed. Although the evidence for the more promising alternatives needs to be developed much further, drugs such as cholinesterase inhibitors may offer a much less harmful alternative. The reluctance of clinicians to use cholinesterase inhibitors in this way is puzzling, and presumably is because of the culture of "guidance-prescribing" that has evolved around these agents. If the treatment of BPSD is to move forward, we need to challenge the way we have always done things, examine the evidence and move forward with new and flexible multi-disciplinary approaches if we are truly to look after the "best interests of our patients".
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PMID:Drugs used to relieve behavioral symptoms in people with dementia or an unacceptable chemical cosh? Argument. 1594 89