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Biomedical subjects

A S Salim

Publications and source records attributed to A S Salim.

At least 19 recordsLinked to original sources

Role of sulfhydryl-containing agents in the healing of erosive gastritis and chronic gastric ulceration in the rat.

One milliliter of 1, 2, or 5% DL-cysteine (cysteine) or DL-methionine methylsulfonium chloride (MMSC) was instilled into the rat stomach 1, 24, and 48 h after giving ethanol (1 mL of 40% solution) by gavage. One hour following the administration of ethanol, gastric mucosal injury was seen in all the animals (22.6 +/- 1.1 mm2, mean +/- SEM; n = 10). Twenty-four hours after giving the ethanol, all the rats treated with cysteine or MMSC still had the mucosal injury. Treatment with 2% cysteine or MMSC significantly (p less than 0.01) reduced the extent of this injury (10.2 +/- 0.6 and 10.1 +/- 0.5 mm2, respectively, versus 20.7 +/- 1.2 mm2, mean +/- SEM; n = 10), an action that was similarly achieved by the 5% solutions (10.1 +/- 0.5 and 9.9 +/- 0.3 mm2, respectively, versus 20.7 +/- 1.2 mm2, mean +/- SEM; n = 10). Forty-eight hours following the administration of ethanol, 30% of the animals given 1% cysteine or MMSC still had gastric mucosal injury, which was significantly (p less than 0.001) less extensive than that seen with ethanol alone (3.8 +/- 0.3 and 4.1 +/- 0.3 mm2, respectively, versus 13.1 +/- 0.8 mm2, mean +/- SEM; n = 10). At this time period, however, none of the animals treated with 2 or 5% solutions of cysteine or MMSC still had any injury. Healing of the ethanol-induced injury was confirmed microscopically and was achieved by regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Protection against chronic gastric ulceration in the rat with sulfhydryl-containing agents.

Reserpine (intraperitoneal, 5 mg/kg every day for 5 days) produced chronic ulceration of the rat stomach 2 weeks postdose. Gavage with 1% DL-cysteine or DL-methionine-S-methylsulfonium chloride at 1 mL/day for 2 weeks and 5 days protected against ulceration in 30% of the rats, and this protection extended to 80% of cases with 2% solutions. Similar gavage with 5% solutions protected all rats against ulceration without significantly influencing the basal H+ output [13.1 +/- 0.3 and 14.2 +/- 0.2 mumol for DL-cysteine and DL-methionine-S-methylsulfonium chloride, respectively, versus 15.1 +/- 0.4 mumol (mean +/- standard error of the mean; n = 10)]; that is, cytoprotection was achieved.

Animals

Use of scavenging oxygen-derived free radicals to protect the rat against aspirin- and ethanol-induced erosive gastritis.

Oxygen-derived free radicals are cytotoxic and produce tissue damage. The effect of the radical scavengers allopurinol and dimethyl sulfoxide (DMSO) on aspirin- and ethanol-induced acute gastric mucosal injury was studied in the rat. Orogastric instillation of aspirin at 200 mg/kg produced, after 4 h, gastric mucosal injury in 30% of rats without pyloric ligation [score, 3.1 +/- 0.8 mm2, mean +/- standard error of the mean (SEM); n = 10] and in 80% of rats with this ligation (score, 10.4 +/- 1.2 mm2, mean +/- SEM; n = 10). Gavage with 1 mL of 2 or 5% allopurinol or DMSO at 24 h before and again just before aspirin administration completely protected rats with or without pyloric ligation against injury. Orogastric instillation of ethanol (1 mL of a 40% solution) produced, after 1 h, gastric mucosal injury in all rats with or without pyloric ligation (24.1 +/- 1.7 and 14.1 +/- 1.3 mm2, respectively, mean +/- SEM; n = 10). Gavage with 1 mL of 5% allopurinol or DMSO at 24 h before and again just before ethanol administration completely protected rats with or without pyloric ligation against injury. Protection against the aspirin- and ethanol-induced injury was not associated with any significant effect on the H+ output. The results suggest that oxygen-derived free radicals are directly implicated in the mechanism of aspirin- and ethanol-induced acute gastric mucosal injury and that scavenging these free radicals protects against injury by maintaining the integrity of the gastric mucosa.

Allopurinol

Stimulation of healing by free radical scavengers of ischemia-induced acute gastric mucosal injury in the rat.

Allopurinol and dimethyl sulfoxide (DMSO; 1 mL of 1, 2, or 5% by gavage daily) were used to examine the influence of scavenging oxygen-derived free radicals on the healing of reserpine- (5 mg/kg, intraperitoneal) and 5-hydroxytryptamine- (50 mg/kg, intraperitoneal) induced acute ischemic injury of the rat gastric mucosa. Allopurinol and DMSO demonstrated a time- but not dose-dependent power to stimulate healing of this injury. The magnitude of injury produced by reserpine or 5-hydroxytryptamine (serotonin) followed by gavage with allopurinol or DMSO was significantly (p < 0.01) less after day 4 than that after day 3 of this gavage, and the magnitude after day 3 was itself significantly (reserpine, p < 0.001; 5-hydroxytryptamine, p < 0.01) less than that after day 2 of the same gavage. The actions of allopurinol and DMSO were not associated with any significant influence on H+ output. These results suggest that oxygen-derived free radicals are detrimental to the integrity of the rat gastric mucosa and that scavenging them stimulates healing of the ischemia-induced injury of the mentioned mucosa.

Allopurinol

Role of sulphydryl-containing agents in the management of venous (varicose) ulceration. A new approach.

This randomized double-blind controlled study examined whether sulphydryl-containing agents influence the healing of venous ulceration occurring for the first time on the medial side of the leg. Graduated compression bandaging, which exerted a mean ankle pressure of 40.6 +/- 0.4 mmHg, and a mean below-knee pressure of 17.1 +/- 0.2 mmHg, healed 70% of ulcers within 12 weeks (n = 46). The addition of the sulphydryl-containing agents DL-cysteine (n = 46) or DL-methionine-methyl sulphonium chloride (n = 45) to the compression bandaging (daily application of the powder for 7 days, followed by once weekly applications until the end of the study 3 months later) significantly (P < 0.01) stimulated healing of venous ulceration relative to control values when studied 4, 8 and 12 weeks after commencing treatment. After 3 months of treatment, both sulphydryl-containing compounds healed 93% of the ulcers. The results show that sulphydryls stimulate healing of venous ulceration.

Adult

Choledochoplasty by vein grafts in iatrogenic bile duct injuries.

The quality of immediate repair of common bile duct injuries with or without tissue loss occurring during elective cholecystectomy is crucial and maybe the sole factor behind future stricture formation with its considerable morbidity and mortality. Successful repair of iatrogenic common bile duct injuries has been achieved by immediate saphenous vein grafts in two patients with cystic duct avulsion, in one patient whose duct was split by a balloon catheter, and in one patient where a segment of the duct was resected. Follow-up for 5 years demonstrated that the grafting remained sound and produced no complications. Consequently, the immediate repair of iatrogenic bile duct injuries using vein grafts deserves consideration.

Adult

Sulphydryl-containing agents stimulate the healing of duodenal ulceration in man.

This prospective randomized double-blind study examined whether sulphydryl-containing agents stimulate the healing and prevent the recurrence of duodenal ulceration in man. To this end, DL-methionine methyl sulphonium chloride (MMSC, 500 mg four times daily) or DL-cysteine (200 mg four times daily) were orally administered with cimetidine. Symptomatic endoscopy-proven duodenal ulcer patients who were smokers and social drinkers were randomized to receive for 8 weeks cimetidine (400 mg b.d.), cimetidine (400 mg b.d.) with MMSC, or cimetidine (400 mg b.d.) with cysteine. These patients were then kept on their respective oral regimens (except for cimetidine which was changed to 400 mg at bedtime) for 1 year (maintenance) and followed up for another. After 8 weeks of treatment, the ulceration healed in 65 patients (74%) given cimetidine alone but in all the patients given MMSC (n = 87) or cysteine (n = 86) with cimetidine (p less than 0.01). During the maintenance year, 15 patients (29%) given cimetidine at night relapsed. Addition of MMSC or cysteine to cimetidine incurred a significantly (p less than 0.001) lower relapse rate. During the year following maintenance therapy, the relapse rate in the group that had been previously treated with cimetidine alone (63%, n = 51) was significantly (p less than 0.001) higher than that in the groups previously treated with MMSC and cimetidine (6%, n = 67) or cysteine with cimetidine (6%, n = 64). The results suggest that sulphydryl-containing agents stimulate the healing and protect against the recurrence of duodenal ulceration.

Adolescent

Sulphydryl-containing agents: a new approach to the problem of refractory peptic ulceration.

Refractory peptic ulceration is the term applied to those gastric and duodenal ulcers which remain unhealed despite active treatment for at least 3 months. Sulphydryl-containing agents stimulate the formation of gastrointestinal mucus, bind the oxygen-derived free radicals that mediate tissue damage and play an important role in protein synthesis. This is the first report which suggests that these agents stimulate the healing of refractory gastric and duodenal ulceration without any adverse events.

Adult

Role of sulphydryl-containing agents in the management of recurrent attacks of ulcerative colitis. A new approach.

This double-blind randomised study investigated the role of sulphydryl-containing agents in the management of recurrent attacks of ulcerative colitis. To this end, DL-cysteine (200 mg 4 times daily) and DL-methionine-methyl sulphonium chloride (MMSC, 500 mg 4 times daily) were administered orally. Patients with recurrent attacks of moderate proctosigmoidal ulcerative colitis, despite prophylaxis by oral sulphasalazine (2 g daily), were given prednisolone by mouth, 10 mg four times a day, sulphasalazine by mouth, 500 mg four times a day, and morning and evening retention enema (Predsol 20 mg) alone or with cysteine or MMSC. After 2 weeks of treatment with sulphasalazine and prednisolone, 51% of patients (n = 45) were symptom free. Addition of cysteine (n = 46) or MMSC (n = 47) to this regimen controlled the symptoms within 2 weeks in 85% of patients (p < 0.01). During 12 months of prophylactic treatment, 5% of patients (n = 42) receiving sulphasalazine (2 g daily) and cysteine and 5% of patients (n = 41) taking sulphasalazine (2 g daily) and MMSC relapsed, relative to 27% of cases with sulphasalazine (2 g daily) alone (p < 0.01). These results demonstrate that sulphydryl-containing agents play a key role in the treatment of and protection against ulcerative colitis.

Adult

Removing oxygen-derived free radicals delays hepatic metastases and prolongs survival in colonic cancer. A study in the rat.

This study examined the influence of the oxygen-derived free radical removing agents allopurinol and dimethyl sulphoxide (DMSO) on the occurrence of hepatic metastases and on the survival rate in the rat with 1,2-dimethylhydrazine (DMH)-induced colonic tumours. At 10 weeks of age, rats were subcutaneously injected every week with 10 mg per kg body weight of DMH for 28 weeks. This produced colonic carcinoma in 80% of animals. The rats that were at this stage continued on their drinking water developed multiple hepatic metastases within 3 months and died at the age of 14.9 +/- 0.3 months (mean +/- SEM). Administration of 1,2 or 5% allopurinol or DMSO for drinking after production of the colonic tumours prevented the development of hepatic metastases 3 months later and significantly (p less than 0.01) extended survival to at least 22.1 +/- 0.1 months of age (mean +/- SEM). The results suggest that in the rat with colonic carcinoma, removing oxyradicals impairs the development of hepatic metastases and prolongs survival.

1,2-Dimethylhydrazine

Oxygen-derived free-radical scavengers prolong survival in colonic cancer.

The influence of scavengers of oxygen-derived free radicals on survival in colonic cancer was studied. Following curative surgery for carcinoma of the sigmoid colon at Dukes' stage C, 198 patients making an uneventful recovery from surgery were randomized to the control group or to receive allopurinol (50 mg orally 4 times a day) or dimethyl sulphoxide (DMSO, 500 mg orally 4 times a day). In 144 fully evaluable patients who were studied for 5 years, allopurinol and DMSO incurred a significant (p less than 0.01) survival advantage over the whole period of study. The similarity in efficacy between allopurinol and DMSO and the fact that the only action they share is scavenging oxyradicals, suggest that these radicals are implicated in the detrimental effects of malignancy and that removing them provides a survival advantage in patients bearing colonic carcinoma.

Adult

Oxygen-derived free-radical scavengers prolong survival in gastric cancer.

The influence of oxygen-derived free radical scavengers on survival in gastric cancer, with serosal invasion and metastases to the lymph nodes surrounding the stomach, was assessed in a prospective randomized controlled double-blind trial conducted for 5 years. To this end, allopurinol (inhibits the enzyme xanthine oxidase which is responsible for the formation of superoxide radicals and scavengers hydroxyl radicals) and dimethyl sulphoxide (DMSO; scavengers hydroxyl radicals) were used. Following potentially curative distal two-thirds partial gastrectomy, 228 patients making an uneventful recovery from surgery were randomized to the control group or to receive allopurinol (50 mg by mouth 4 times a day) or DMSO (500 mg by mouth 4 times a day). In 160 fully evaluable patients who were studied for 5 years, allopurinol and DMSO incurred a significant (p less than 0.01) survival advantage over the whole period of study. The similarity in efficacy between allopurinol and DMSO and the fact that the only action they share is scavenging oxyradicals suggest that these radicals mediate the aggressiveness of gastric cancer by producing tissue damage, thus allowing the cancer to spread. Consequently, oxygen-derived free radicals are implicated in the mechanism of gastric cancer, and removing them provides patients with a survival advantage.

Adult

Role of 5-hydroxytryptamine (5-HT) in the mechanism of reserpine-induced stimulation of H+ output in the rat. A new hypothesis for the mechanism of gastric acid secretion.

This study was undertaken in the rat to examine the role of 5-hydroxytryptamine (5-HT) in the mechanism of reserpine (0.1 mg/kg)-induced stimulation of gastric acid secretion. Reserpine significantly (p < 0.001) stimulated acid secretion relative to control values (197 +/- 3.1 vs 61 +/- 1.7 mumol, mean +/- SEM, n = 10). Atropine (5 mg/kg) and cimetidine (40 mg/kg) were equally effective in achieving a significant (p < 0.001) suppression of the reserpine-induced acid secretion (98 +/- 3.4 and 91 +/- 2.9 mumol, respectively, vs 197 +/- 3.1 mumol, mean +/- SEM, n = 10), an action intensified by administering them together, but not significantly so (84 +/- 5.3 mumol). Vagotomy was more effective (p < 0.001) than the latter combination in preventing acid stimulation by reserpine and allowed an acid output similar to that of vagotomy controls (14 +/- 1.2 vs 13 +/- 1.4 mumol, mean +/- SEM, n = 10). Dose dependent inhibition of the reserpine-induced stimulation of acid secretion was achieved by the 5-HT receptor antagonist methysergide, an inhibition significantly (p < 0.001) more effective than that afforded by vagotomy coupled with achlorhydria in 80% of animals was noted with the 5-20 mg/kg doses. Reserpine produces vagal adrenergic delivery to the stomach, which releases acid secretagogues and sensitizes parietal cells to them besides stimulating acid secretion, and 5-HT is discharged into the gastric mucosa by vagal adrenergic activity and by reserpine and liberates acid secretagogues by a paracrine action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Is re-communication of vagal branches responsible for the recurrence of duodenal ulceration after proximal gastric vagotomy? A study in the rat.

This study was carried out in the rat to examine whether preventing the re-communication of vagal fibres with their distal stumps after proximal gastric vagotomy (PGV), by placing a patch against the bare area of lesser curvature, impairs the return of gastric secretory patterns to their pre-operative levels and reduces the incidence of duodenal ulceration. PGV alone or with a patch significantly depressed the basal acid output. Administration of insulin (1 unit/kg i.p.) failed to stimulate this output. Two years later, the basal acid output of PGV was significantly (p < 0.05) higher than that of PGV with a patch (7.8 +/- 0.2 vs 3.7 +/- 0.3 mumol, mean +/- SEM), but significantly (p < 0.01) lower than that of the control animals (7.8 +/- 0.2 vs 14.2 +/- 0.8 mumol, mean +/- SEM). Insulin did not stimulate the acid output of PGV with a patch, but significantly (p < 0.001) stimulated the PGV acid output (7.8 +/- 0.2 vs 28.9 +/- 0.6 mumol, mean +/- SEM). This stimulation was significantly (p < 0.001) less than that noted in the control animals. PGV alone or with a patch equally prevented acid stimulation and production of duodenal ulceration by the infusion of pentagastrin (4 micrograms/kg/min) and carbachol (0.8 microgram/kg/min) for 24 hours. Two years later, these secretagogues significantly (p < 0.001) stimulated acid secretion in the PGV group relative to control values (24.1 +/- 2.3 vs 13.9 +/- 0.5 mumol, mean +/- SEM) and produced duodenal ulceration in 19% of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Role of oxygen-derived free radical scavengers in the management of recurrent attacks of ulcerative colitis: a new approach.

This double-blind, randomized study investigated the role of oxygen-derived free radical scavengers in the management of recurrent attacks of ulcerative colitis. To this end, allopurinol (50 mg four times a day) and dimethyl sulfoxide (500 mg four times a day) were administered orally. Patients with recurrent attacks of moderate proctosigmoidal ulcerative colitis, in spite of prophylaxis with orally administered sulfasalazine (2 gm daily), were given 10 mg prednisolone by mouth four times a day; 500 mg sulfasalazine by mouth four times a day; and morning and evening retention steroid enema (Predsol, 20 mg) alone or with allopurinol or dimethyl sulfoxide. After 2 weeks of treatment with sulfasalazine and prednisolone alone, 51% of patients (n = 45) were free of symptoms. Addition of allopurinol (n = 46) or dimethyl sulfoxide (n = 45) to the mentioned regimen controlled the symptoms within 2 weeks in 84% of patients (p less than 0.01). During 12 months of prophylactic treatment, 5% of patients (n = 42) who were given sulfasalazine (2 gm daily) and allopurinol and 5% of patients (n = 40) who were given sulfasalazine (2 gm daily) and dimethyl sulfoxide relapsed compared with 25% of patients who were given sulfasalazine (2 gm daily) alone (p less than 0.05). The results suggest that oxygen-derived free radicals may be involved in the mechanism of ulcerative colitis and that removing them may be useful in the treatment of attacks and in protecting the colon against recurrence of attacks.

Adult

Allopurinol and dimethyl sulfoxide improve treatment outcomes in smokers with peptic ulcer disease.

This prospective, randomized, double-blind study examined whether scavengers of oxygen-derived free radicals are of benefit in the treatment of acute duodenal ulceration in human beings. To this end, allopurinol (50 mg four times a day), a hydroxyl radical scavenger and an inhibitor of xanthine oxidase that forms superoxide radicals, and dimethyl sulfoxide (500 mg four times daily), a hydroxyl radical scavenger, were administered orally with cimetidine. Patients with symptomatic endoscopy-proven acute duodenal ulceration who were smokers and social drinkers were randomized to receive for 8 weeks cimetidine (400 mg two times a day), cimetidine (400 mg two times a day) with dimethyl sulfoxide, or cimetidine (400 mg two times a day) with allopurinol. These patients were then kept on their respective oral regimens (except for those who received cimetidine, for whom the dose was changed to 400 mg at bedtime) for 1 year (maintenance) and followed up for another. After 8 weeks of treatment, the ulceration healed in 69 of the patients (79%) who were given cimetidine alone and in all of the patients who were given dimethyl sulfoxide (n = 85) or allopurinol (n = 84) with cimetidine (p less than 0.01). During the maintenance year, 15 patients (29%), who were given cimetidine nightly, relapsed. Addition of dimethyl sulfoxide or allopurinol to cimetidine was associated with a significantly lower (p less than 0.001) relapse rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult