Domperidone: review of pharmacology and clinical applications in gastroenterology

Domperidone is a dopamine-2 receptor antagonist. It acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function of the stomach and small intestine. Unlike metoclopramide, it does not cause any adverse neurological symptoms as it has minimal penetration through the blood-brain barrier. It thus provides an excellent safety profile for long-term administration orally in the recommended doses. Domperidone is widely used in many countries and can now be officially prescribed to patients in the United States by an investigational new drug application for the treatment of gastroparesis and any condition causing chronic nausea and vomiting. In view of this additional clinical exposure of domperidone to a new generation of gastroenterologists and other specialists, the purpose of this timely review is to revisit the pharmacology, clinical application, and safety profile of this beneficial medication.     

Long term administration of granulocyte-macrophage colony stimulating factor decreases development of 1-2 dimethylhydrazine-induced colon cancer in rats

BACKGROUND AND OBJECTIVES: The antitumoral activities of granulocyte-macrophage colony stimulating factor (GM-CSF) were shown earlier. In this study, the effects of GM-CSF were investigated on colon cancer induced by 18 weeks of 1-2 dimethylhydrazine (DMH) administration in rats. METHODS: Four groups received subcutaneous saline (n = 20), 15 mg/kg DMH (n = 30), DMH +6 microg/kg GM-CSF (n = 30), and DMH +12 microg/kg (n = 30) GM-CSF. RESULTS: The average number of tumors (2.8 vs. 1.5) and mean tumor volume (179 +/- 36 vs. 27 +/- 9 mm(3); means +/- SEM) were reduced in DMH + GM-CSF groups as compared to the DMH group (n = 30, P < 0.01). DMH-induced enhancement of free radicals and lipid peroxidation were decreased in DMH + GM-CSF group (n = 8-12, P < 0.05). The magnitude of DMH-induced alterations in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities was lowered in the DMH + GM-CSF group (n = 12-16, P < 0.05). DMH-induced increases in the total nitrite/nitrate levels and the nitric oxide synthase (NOS) activity (n = 10-12, P < 0.05) were also reduced in the DMH + GM-CSF group (n = 8-9, P < 0.05). CONCLUSIONS: The results indicate that GM-CSF inhibits the development of DMH-induced colon cancer in rats and suggest that inhibition of oxidative stress and NO pathway are involved in the observed antitumoral effects.     

Agmatine produces antinociception in tonic pain in mice.

Agmatine is an endogenous polyamine metabolite formed by decarboxylation of L-arginine. In this study, the effect of agmatine on tonic pain was compared to its effect on phasic pain by using the formalin and tail-flick (TF) tests in mice. When administered intraperitoneally (ip), agmatine (37.5-300 mg/kg) exhibited a decrease in nociceptive behaviours in the first and second phase of the formalin test, which is a tonic pain model. The alpha(2) adrenoceptor antagonist yohimbine blocked the effect of agmatine in Phase 2 but did not change its effect in Phase 1. In the TF test, there was no significant change in the behaviour of agmatine-administered (75-300 mg/kg) animals. As a result, agmatine appears to have an analgesic effect on tonic rather than phasic pain, and alpha(2) receptors seem partly to have a role in the antinociceptive effect of agmatine on tonic pain.     

Local Granulocyte-Macrophage Colony-Stimulating Factor Improves Incisional Wound Healing in Adriamycin-Treated Rats

Purpose Neoadjuvant treatment is often given for locally advanced malignancies; however, clinical and experimental studies have shown that some chemotherapeutic agents impair wound healing. It has been reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) applied locally improves dermal wound healing. Thus, we investigated the effects of locally injected GM-CSF on abdominal wounds impaired by adriamycin, a widely used chemotherapeutic agent. Methods We divided 120 female Sprague-Dawley rats into five treatment groups of 24 rats. Group 1 received saline 8 mg/kg intravenously (i.v.) + laparotomy 14 days later (control); group 2 received 8 mg/kg i.v. adriamycin + laparotomy 14 days later; group 3 received adriamycin 8 mg/kg i.v. + laparotomy + local GM-CSF 50 μg 14 days later; group 4 received saline 8 mg/kg i.v. + laparotomy + local GM-CSF 50 μg 14 days later; and group 5 received adriamycin 8 mg/kg i.v. + laparotomy + systemic GM-CSF 50 μg 14 days later. Sutures were removed on postoperative day (POD) 7 in all five groups, and the abdominal bursting pressures were measured and recorded. Tissue samples were taken from the incision line for histopathological evaluation and hydroxyproline content measurement. Results The bursting pressure was significantly lower in groups 2 and 5 than in groups 1, 3, and 4. The hydroxyproline content and histopathological findings supported this result. Conclusion The local injection of GM-CSF improved impaired wound healing in adriamycin-treated rats.     

The reliability and validity of Arizona sexual experiences scale in Turkish ESRD patients undergoing hemodialysis

Although sexuality was the fifth most important life stressor cited by dialysis patients, sexual dysfunctions (SD) receive a very limited attention in the follow-up of these patients. The main aim of the present study was to investigate the reliability and validity of the Arizona Sexual Experiences Scale (ASEX) for end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) in Turkey. The instrument's reliability and validity were assessed in 43 ESRD outpatients undergoing dialysis. All patients were assessed at baseline and at 6 months. ASEX showed good internal consistency (Cronbach's alpha's 0.89 and 0.90) and test-retest reliability (r=0.88, P<0.001). Convergent validity of ASEX was measured by means of the scales' correlation with the psychiatrists' assessment for the presence of SD (r=0.53, P<0.001). The results of receiver operating characteristics analysis for criterion validity revealed that ASEX scores could discriminate well (0.85+/-0.06 (95% confidence interval, 0.73-0.90), P<0.001) between patients with 'no SD (n=26)' and 'with SD (n=17)'. A total ASEX score of < or =11 was found to be the best cutoff point (sensitivity=100%, specificity=52%) for screening in this group of patients. The findings of this study indicate that the ASEX is a valid and reliable instrument for use in clinical trials on sexual functioning of ESRD patients undergoing HD.     

Nd:YAG laser iridotomy in the management of secondary glaucoma associated with Behçet's disease

PURPOSE: To report the outcome of Nd:YAG laser iridotomy in the management of secondary glaucoma associated with Beh?et's disease (BD). METHODS: In this prospective study, Nd:YAG laser iridotomy was performed on eyes with secondary angle-closure and pupillary block glaucoma associated with BD. The pretreatment and post-treatment intraocular pressures (IOP) and the number of antiglaucoma medications were compared by Mann-Whitney U test. RESULTS: The study consisted of 16 eyes of 11 patients (2 female, 9 male, mean age 39.2+/-8.9 years). Post-treatment follow-up ranged from 6 to 36 months (mean 13.8+/-8.9). The mean IOP was 21.6+/-2.5 mmHg on 2.5+/-0.6 medications before iridotomy. IOP reduced to 17.7+/-2.5 mmHg on 1+/-0.6 medications at the first month and 17.1+/-3.2 mmHg on 1.7+/-0.9 medications at the sixth month of treatment. The differences between IOP and number of antiglaucoma medications at baseline and at the sixth month of the treatment was statistically significant (p<0.00001). For four eyes trabeculectomy with mitomycin C and for one eye Ahmed valve implantation were performed in the follow-up period. CONCLUSIONS: Nd:YAG laser iridotomy can provide reduction of IOP and the number of antiglaucoma medications in selected cases with secondary glaucoma associated with Behcet's disease.     

Effect of β-Glucan on Drain Fluid and Amount of Drainage Following Modified Radical Mastectomy

Introduction

To reduce the seroma formation following mastectomy and axillary dissection, many different techniques and drugs have been investigated. The aim of this study is to evaluate the effects of oral β-glucan on drain fluid and efficacy of daily drainage and drain removal day in mastectomy patients.

Methods

One hundred and thirty breast cancer patients of Ankara Oncology Training and Research Hospital were divided into 2 groups by consecutive randomization (n = 65 each). β-glucan 10 mg capsules were administered to Group 1 twice a day for 10 days. Group 2 took placebos in the same manner. Age, menarche age, menopause, parity, history of oral contraceptives, comorbidities, postoperative daily drainage volumes and drain removal days were recorded and compared. Seroma samples during the first and second day of drainage were taken for analysis of Interleukin-6 (IL-6) and Tumor Necrosis Factor (TNF-α).

Results

There was no difference between groups in terms of age, menarche age, menopause period, parity, oral contraceptive use and comorbidities. Group 1 showed significantly lower daily drainage volumes between days 2 and 8. Mean drain removal day was 7.16 ± 1.72 in Group 1 and 8.59 ± 2.27 in Group 2. The difference was significant (p < 0.001). TNF-α and IL-6 levels on days 1 and 2 in Group 1 were significantly lower (p < 0.001). In addition, β-glucan significantly shortened the number of days required for the drain removal in patients who have comorbidities (p = 0.018). The earliest removal was in patients without comorbidity and who received β-glucan (p = 0.002).

Conclusion

β-glucan decreased drain discharges after mastectomy. The drains were removed earlier in β-glucan administered patients.     

Is combined therapy more effective than growth hormone or hyperbaric oxygen alone in the healing of left ischemic and non-ischemic colonic anastomoses?

OBJECTIVE:

Our aim was to investigate the effects of growth hormone (GH), hyperbaric oxygen and combined therapy on normal and ischemic colonic anastomoses in rats.

METHODS:

Eighty male Wistar rats were divided into eight groups (n = 10). In the first four groups, non-ischemic colonic anastomosis was performed, whereas in the remaining four groups, ischemic colonic anastomosis was performed. In groups 5, 6, 7, and 8, colonic ischemia was established by ligating 2 cm of the mesocolon on either side of the anastomosis. The control groups (1 and 5) received no treatment. Hyperbaric oxygen therapy was initiated immediately after surgery and continued for 4 days in groups 3 and 4. Groups 2 and 6 received recombinant human growth hormone, whereas groups 4 and 8 received GH and hyperbaric oxygen treatment. Relaparotomy was performed on postoperative day 4, and a perianastomotic colon segment 2 cm in length was excised for the detection of biochemical and mechanical parameters of anastomotic healing and histopathological evaluation.

RESULTS:

Combined treatment with hyperbaric oxygen and GH increased the mean bursting pressure values in all of the groups, and a statistically significant increase was noted in the ischemic groups compared to the controls (p<0.05). This improvement was more evident in the ischemic and normal groups treated with combined therapy. In addition, a histopathological evaluation of anastomotic neovascularization and collagen deposition showed significant differences among the groups.

CONCLUSIONS:

Combined treatment with recombinant human growth hormone and hyperbaric oxygen resulted in a favorable therapeutic effect on the healing of ischemic colonic anastomoses.