Cimetidine

Immune suppression occurs frequently after major injury and undoubtedly contributes to infection and mortality in trauma patients. Prevention of such suppression may lead to decreased infection and improved survival in trauma patients surviving the immediate insult of injury. Suppressor-cell activation appears to play a key role in immune suppression after major injury. For several years we have studied the effects on immune functions after injury of various drugs which have been shown in the immunologic literature to have inhibitory effects on suppressor cell populations. H2-antagonists may inhibit suppressor cell activation by blocking surface H2-receptors, which are present in higher numbers on suppressor cells than on helper cells. Prostaglandin inhibitors may block the multiple immune suppressive effects of prostaglandins, particularly PGE2. Immunological studies suggest that low-dose cyclophosphamide selectively inhibits the proliferation of suppressor T cells. Our previous work suggested that such drugs preserve cell-mediated immune functions after injury. In experiments reported here, we utilized a standard hindlimb crush injury and amputation in mice, followed in 24 hrs by polymicrobial septic challenge using cecal ligation and 23-gauge needle puncture (CLP). Nontraumatized (control) mice had a 36.2% mortality after CLP; when crush injury/amputation was followed by CLP in 24 hrs the mortality rose to 63.8% (p less than 0.0035). When mice were given 24 hrs before crush/amputation: cimetidine, an H2-antagonist (10 mg/kg/day); ibuprofen, a prostaglandin blocker (5 mg/kg/day); or cyclophosphamide (2.5 mg/kg/day), and a second dose on the day of trauma, with CLP 24 hrs later, subsequent mortality was not different from the mortality in nontraumatized, control mice (p less than 0.0035).(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the study was to evaluate the antiulcer activity of Linum usitatissimum fixed oil against aspirin-, indomethacin-, ethanol-, reserpine-, serotonin- and stress-induced gastric ulceration in rats and histamine-induced gastric ulceration in guinea pigs. Attempts were also made to evaluate the in vitro anticholinergic and antihistaminic activity and in vivo antisecretary and antiulcer activity of oil following pylorus ligation in rats. L. usitatissimum fixed oil exhibited significant antiulcer activity against different ulcerogens in experimental animal models. The fixed oil significantly inhibited acetylcholine- and histamine-induced contraction of guinea pig and rat ileums, respectively, suggesting its anticholinergic and antihistaminic activity. The oil also exhibited significant inhibitory effect on gastric secretion/total acidity and aspirin-induced gastric ulceration in pylorus-ligated rats. The lipoxygenase inhibitory, histamine antagonistic and antisecretory (anticholinergic) effects of the oil could probably have contributed towards antiulcer activity. L. usitatissimum fixed oil may be considered to be a drug of natural origin which possesses significant antiulcer activity. The present observation is the first experimental data showing antiulcer activity of L. usitatissimum fixed oil.

A simple and rapid assay based on hydrophilic interaction liquid chromatography with tandem mass spectrometry has been first developed and validated for simultaneous determination of caprolactam (CA) and 6-aminocaproic acid (6-ANCA) in human urine using 8-aminocaprylic acid as internal standard. A 20μL aliquot of urine was injected directly into the liquid chromatography tandem mass spectrometry (LC-MS-MS) system. The analytes were separated on a Phenomenex Luna HILIC column with gradient elution. Detection was performed on Triple Quadrupole LC-MS in positive ions multiple reaction monitoring mode using electrospray ionization. The calibration curves were linear (r(2)≥0.995) over the concentration range from 62.5 to 1250ng/mL for CA and 31.25 to 1000ng/mL for 6-ANCA. The detection limits of CA and 6-ANCA were 62.5 and 15.6ng/mL, respectively. The intra-day and inter-day precisions were within 8.7% and 9.9%, respectively. The intra-day and inter-day accuracy were between 5.3% and 3.5...

To enhance our understanding of the uterotonic effect of histamine, we compared the effects of histamine on spontaneous phasic and tonic contractile activity of uterine strips from term pregnant nonlaboring women. Longitudinal uterine strips were used from the lower uterine segment of term pregnant nonlaboring women undergoing elective cesarean section. The concentration-response relationship to histamine (10(-8) to 10(-4) mol/L) was determined in spontaneously contracting strips or in strips contracted tonically with a protein kinase C activator (-)-indolactam V in the presence of H(1) receptor antagonist (S[+]-chlorpheniramine maleate), H(2) receptor antagonist (cimetidine), or solvent. Histamine increased spontaneous phasic myometrial contractions in a concentration-dependent manner. H(1), but not H(2), receptor antagonist significantly attenuated the response to histamine. Histamine significantly reduced tonic contractions of uterine strips induced by indolactam V. H(1) histamine receptor antagonist abolished relaxation, whereas H(2) histamine receptor antagonist had no effect. Histamine increases spontaneous, but inhibits tonic, contractions of uterine strips from term pregnant nonlaboring women. Both effects are mediated through activation of H(1) receptors.

The usefulness of the joint application of HPLC and NMR spectroscopy in drug impurity profiling is demonstrated by the following examples: (1) identification of Z and E isomers of 17α-ethynyl-4-oestrene-3β,17-diol-3- acetate-17-(3′-acetoxy-2′-butenoate) in ethynodiol diacetate; (2) identification of the p-tolyl analogue as the impurity of enalapril maleate; (3) identification and quantification of 2′-dehydro-pipecuronium bromide in pipecuronium bromide. The possibilities of utilizing NMR spectroscopy for the identification and quantification of the impurities with and without their isolation are discussed.

We have previously shown that cimetidine, given concurrently for 2 weeks to patients on chronic dapsone therapy, reduced methaemoglobinaemia by inhibiting the formation of the toxic hydroxylamine metabolite of dapsone. The aim of the present study was to examine the effect of this combination on the benefit/toxic ratio of dapsone over a longer period. Eight patients (six dermatitis herpetiformis, one linear IgA disease, one folliculitis decalvans) on long-term dapsone 50-100 mg daily, took cimetidine 1.6 g daily concurrently for 3 months. At 3-weekly intervals, a clinical assessment was made, plasma dapsone and methaemoglobin were measured, and parameters of oxidative haemolysis were monitored. The dapsone level rose from 2298 +/- 849 ng/ml (mean +/- SD) at baseline to 3006 +/- 1131 ng/ml at week 3 of cimetidine (P < 0.01). This rise in plasma dapsone was sustained during cimetidine administration, falling to 2446 +/- 954 ng/ml when cimetidine was stopped (P < 0.02). The methaemoglobin fell from 5.5 +/- 2.2% (mean +/- SD) at baseline to 3.9 +/- 1.1% at week 3 (P < 0.01), and remained low until week 12, when there was a return to baseline values (P < 0.01). The haemoglobin did not change from the baseline of 12.7 +/- 0.3 g/dl (mean +/- SD), and other parameters of haemolysis were unaltered. There was a fall in the visual analogue score for headache (P < 0.05), but this was not associated with any deterioration in control of the skin disorders. Hence, long-term concurrent cimetidine results in increased plasma dapsone levels without increased haemolysis, and is accompanied by reduced methaemoglobinaemia for more than 2 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: To examine the site, severity, and duration, of symptoms in patients with interstitial cystitis. To examine the treatments offered. Materials and methods: Postal questionnaire administered to members of the Interstitial Cystitis Support Group, based in the United Kingdom. Results: 736 of 1148 (64%) questionnaires were returned. 696 (94.6%) patients were women. 471 patients (64%) described daily pain when symptoms were at their worst, and 273 (37%) described daily pain at the time of survey. Most patients reported frequency, urgency and nocturia. A wide range of treatments had been offered, but drugs of proven efficacy were offered to less than a third of patients: cimetidine (36%); antihistamines (5%); pentosan polysulphate (12%); DMSO (33%); and anticonvulsants (2%). 495 patients (67%) reported “considerable impact” or more on their lifestyle and 346 (46%) reported moderate depression or worse. 364 (49%) reported at least considerable difficulties with sexual intercourse. Conclusions: This survey supports the work of others about the nature of symptoms and their impact upon quality of life. The data highlight the continuing difficulty in making a prompt diagnosis. We recommend that a European survey or registry of interstitial cystitis patients would help to establish a minimum standard of care. A suggested treatment algorithm is provided.

The peritoneal mesothelium is a barrier to ion transport in peritoneal dialysis. Cimetidine is an H2 receptor antagonist and a potent inhibitor of Na+/H+ antiporter, which is found in the plasma membranes of various cell types, including mesothelial cells. Recent reports linked Na+/H+ antiporter stimulation with increasing peritoneal fibroblast proliferation. The aim of the present study was to investigate by means of Ussing chamber experiments the effect of cimetidine on the transmesothelial electrical resistance (R) of isolated visceral sheep peritoneum. Peritoneal samples obtained from adult sheep were collected from the slaughterhouse and transferred in oxygenated Krebs-Ringer bicarbonate (KRB) solution to the laboratory within 30 minutes of the animal's death. The peritoneal tissue was transferred in a cooled KRB solution (4 degrees C, pH 7.5) bubbled with 95% O2/5% CO2. A planar sheet of the visceral peritoneum was mounted in an Ussing-type chamber and cimetidine (10(-3) m...

To investigate the weight-reducing effect of cimetidine in overweight patients with Type 2 diabetes. A 12-week clinical intervention study of 400 mg cimetidine prescribed three times daily in a randomised, double-blind, placebo-controlled design. Forty-three overweight patients with Type 2 diabetes (age 18-65 y, body mass index (BMI) 27.2-48.2 kg/m2). Body weight, BMI, body fat, waist and hip circumference, waist/hip ratio, blood pressure, fasting blood glucose, HbA1c, plasma concentrations of insulin, insulin/glucose ratio and lipids at the start and after 12 weeks, and daily recordings of appetite. Subjects given cimetidine (n = 19) and placebo (n = 24) lost 5.0 +/- 2.2 kg (mean +/- s.d.) and 1.3 +/- 1.1 kg, respectively. Significant reductions were observed in appetite, body fat (29.9 +/- 6.6% to 25.3 +/- 7.4%), waist circumference (111.5 +/- 10.3 cm to 107.4 +/- 10.6 cm), waist/hip ratio (0.96 +/- 0.08 to 0.94 +/- 0.08), and systolic and diastolic blood pressure (reductions of 6...