Epithelial ulceration

Toxicity Adherence of the suspension to areas of epithelial ulceration or retention in the fornices occurs regularly. Should suspicion of drug toxicity occur, discontinue the drug. 

Noninfectious indolent epithelial ulcers also can occur in HSK.These ulcers, formerly referred to as metaherpetic lesions, tend to be ovoid, 2 to 8 mm in size, with smooth rolled edges. They may be caused by damage to the epithelial basement membrane due to inflammation, tear film abnormalities, neurotropic cornea, or toxicity from antiviral medications. These ulcers may be recalcitrant, resulting in neovascularization and scarring. 

Figure 3.1 A schematic representation of the control mechanism that stimulates gastric acid secretion, and the intervention points used to treat ulcers. The parietal cells and gastric cells form part of the epithelial cell lining of the stomach. Histamine release is usually triggered as part ofthe enteric nervous system response to distension of the stomach when food is eaten.

Ulcer formation is the net result of a lack of homeostasis between factors within the gastrointestinal tract responsible for the breakdown of food (e.g., gastric acid and pepsin) and factors that promote epithelial defense and repair (e.g., bicarbonate, mucus secretion, and prostaglandins). 

Prostaglandins, one of the most important epithelial growth factors, inhibit gastric acid secretion and have numerous mucosal protective effects, the most important of which include the stimulation of both mucus and phospholipid production, promotion of bicarbonate secretion, and increased mucosal cell turnover. Damage to the mucosal defense system is the primary method by which HP or NSAIDs cause peptic ulcers. 

The goals of PUD therapy are to (1) resolve symptoms (2) reduce acid secretion (3) promote epithelial healing (4) prevent ulcer-related complications and (5) prevent ulcer recurrence. For HP-related PUD, eradication of HP is an additional outcome. 

Alterations in mucosal defense induced by HP or NSAIDs are the most important cofactors in peptic ulcer formation. Mucosal defense and repair mechanisms include mucus and bicarbonate secretion, intrinsic epithelial cell defense, and mucosal blood flow. Maintenance of mucosal integrity and repair is mediated by endogenous prostaglandin production. 

Dermal Effects. No studies were located regarding dermal effects in humans after exposure to disulfoton. Dermal lesions consisting of acanthosis, hyperkeratosis, ulceration of the skin, exudate formation, and epithelial inclusion cysts were found in male and female rats exposed chronically to the high dietary concentration of disulfoton (Hayes 1985). However, in intermediate- duration studies,... 

Flalstensen, T.S., et al. (1990). Epithelial deposition of immunoglobulin G and activated complement (C3b and terminal complement complex) in ulcerative colitis. Gastroenterology, 98, 1264-1271. 

All mice and some rats receiving 1600 ppm by inhalation 6 hours/day for up to 13 weeks died. Clinical findings included hypoactivity, abnormal posmre, and, in rats, clonic convulsions. Male mice administered 400 ppm and females given 200 ppm, also for 13 weeks, had focal epithelial hyperplasia and ulceration of the forestomach. 

In mice exposure to 9 ppm caused a 50% decrease in respiratory rate. Lesions included ulceration and necrosis of the respiratory epithelium and moderate damage to lung tissue. Rats administered, via oral gavage, 10, 20, 40, or 80mg/kg for 10 consecutive days or 32 mg/kg for 90 consecutive days had inflammation, necrosis, acantholysis, hyperkeratosis, and epithelial hyperplasia of the forestomach. Chloropicrin was genotoxic in bacterial test systems."... 

In a follow-up study in mice, exposure to DEA, via drinking water or by topical application, caused dose-dependent toxic effects in the liver (hepatocellular cytological alterations and necrosis), kidney (nephropathy and tubular epithelial necrosis in males), heart (cardiac myoqn e degeneration), and skin (site of application ulceration, inflammation, hyperkeratosis, and acanthosis). Doses ranged from 630 to 10,000 ppm in the drinking water and from 80 to 12 50 mg/kg in the topical application study. 

Peptic ulceration occurs as an acute or chronic non-traumatic epithelial breach typically in the gastric or duodenal mucosa, but also in the oesophagus (see above) and occasionally in the small intestine with the Zollinger-Ellison syndrome of gastrin overproduction or with an acid-secreting Meckel s diverticulum. Symptoms overlap with those of non-ulcer dyspepsia and cancer and the diagnostic cornerstone is endoscopy. Biopsy may be necessary to distinguish ulcer from cancer. 

Delayed re-epithelialisation and persistent epithelial defects are typical features of chronic ulcers which hardly heal [31, 37], It has been proposed that excessive and uncontrolled proteolytic activity is an important pathogenesis factor for chronic wounds [44]. Proteolysis is caused mainly by the oxidative stress accompanying an... 

Sucralfate is a basic aluminium salt of sucrose, a complex of sucrose octasulphate and aluminium hydroxide. At acid pH (<4), it forms a very sticky gel polymer, which adheres to epithelial cells and the base of ulcer craters. It has little or no antacid activity, but more importantly has a major cytoprotective action, both protecting the mucosa from damaging influences and also causing accelerated healing. It appears to work through a number of relatively poorly understood mechanisms, enhancing several gastric and duodenal protective mechanisms—different actions may be related to its chemistry as an aluminium salt, and to the sucrose octasulphate component. 

The ulcer of the cornea is the abrasion of the cornea surface, secondary to the epithelial necrosis it may also alter a deeper layer, the comeal stroma. 

The ulcer is evidently visible when there are some epithelial cells left these cells will form the edge of the ulcer. In case of a complete ulcer (necrosis of the epithelial cells), it could be difficult for a neophyte to spot it. The image is the same as the one of a comeal surface looking evenly green, like when there is no ulcer however, this image remains even after a wash with a normal saline solution. 

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