Free fatty acid suppositories are as effective as docusate sodium and sorbitol enemas in treating constipation in children.

AIM: A well-documented, clinically proven per rectum treatment for childhood constipation is needed. This phase two clinical trial evaluated the efficacy of suppositories containing free fatty acids (FFA) compared with Klyx docusate sodium and sorbitol enemas. METHODS: A randomised, controlled, single-blind study was undertaken on 77 children aged between one and 17 who presented to an emergency department in Iceland and were diagnosed with constipation. In stage one, 23 patients were randomised to receive lower dose FFA suppositories or Klyx (n = 33). In stage two, 21 different patients were randomised to receive higher dose suppositories and compared with the same Klyx control subjects. RESULTS: The suppositories were effective at bowel emptying in 39% of the group who received the lower FFA doses and 81% of the group receiving higher doses, compared with 88% in the Klyx control group. Symptom relief was obtained in 30% of the group receiving the lower doses and 71% of the group receiving the higher doses, compared with 73% in the control group. CONCLUSION: The higher dose FFA suppositories were as effective as the Klyx enemas with regard to bowel emptying and symptom relief and might provide an important and less invasive alternative for childhood constipation.

Clinical trial: free fatty acid suppositories compared with enema as bowel preparation for flexible sigmoidoscopy.

OBJECTIVES: The purpose of this trial was to evaluate the efficacy and safety of recently developed suppositories containing free fatty acids as a bowel-cleansing agent prior to flexible sigmoidoscopy and compare them with Klyx (docusate sodium/sorbitol). DESIGN: A controlled, non-inferiority, single-blind, randomised study on outpatients undergoing flexible sigmoidoscopy. SETTING: Department of Gastroenterology, Landspitali-University Hospital and endoscopic clinic. PATIENTS: 53 outpatients undergoing flexible sigmoidoscopy. INTERVENTION: Participants were randomised to receive either free fatty acid suppositories (28) or a standard bowel preparation with Klyx enema (25). In the study group, two suppositories were administered the evening before as well as 2 h prior to the sigmoidoscopy. In the control group, Klyx enema (120 mL) was administered the evening before and repeated 2 h prior to the procedure. MAIN OUTCOME MEASUREMENTS: Quality of the bowel cleansing, height of scope insertion and safety. RESULTS: The mean height of scope insertion and bowel cleansing was 43 cm (SD=13.4) in the study group and 48 cm (SD=10.4) in the control group (NS). The investigating physicians were less satisfied with the bowel preparation in the study group compared with the control group with a difference of 20% (p<0.016). The amount of faeces noted in the rectum was similar in both groups with no significant difference (p<0.56). No serious side effects, toxic reaction or irritation were observed. CONCLUSIONS: The suppositories are well tolerated with no significant side effects. The suppositories had distinct bowel emptying effect and as effective as Klyx in rectal cleansing. Although physician's satisfaction was slightly lower, the height of scope insertion was similar. TRIAL REGISTRATION NUMBER: EudraCT nr.: 2010-018761-35.

GABA agonists fail to protect the retina from ischemia-reperfusion injury.

The purpose of this study was to test the hypothesis that ischemia/reperfusion injury in the rat retina may be ameliorated by reducing retinal metabolism with either hypothermia or inhibitory GABA agonists. The intraocular pressure of each right eye in rats was raised to 130 mm Hg for 60 min with the left eye serving as normal control. The rats were divided into four groups in terms of drug and hypothermia treatment: (1) Untreated ischemia, (2) Hypothermia, (3) Baclofen/midazolam and (4) Baclofen/muscimol. Electroretinogram was recorded before ischemia and again after 10-day reperfusion. Histological analysis with H&E staining and cell counts was performed. Untreated ischemia/reperfusion resulted in severely reduced ERG responses. The ERG b-wave was reduced from 423+/-144 microV to 130+/-91 microV (mean+/-SD, n=5). With hypothermia the ERG b-wave was reduced from 499+/-80 microV to 237+/-111 microV (n=4). With combinations of baclofen and midazolam the ERG b-wave was reduced from 432+/-96 microV to 104+/-67 microV (n=7). In baclofen/muscimol treated eyes the ERG b-wave went from 426+/-101 microV to 148+/-118 microV (n=6). The histological tissue damage was severe in untreated ischemia and the baclofen/midazolam and baclofen/muscimol groups, but less severe in the hypothermia group. The GABA agonists do not provide any protection in our ischemia/reperfusion model. Our results are consistent with earlier reports that hypothermia may be helpful in ischemic conditions in the retina.

Ocular powder: dry topical formulations of timolol are well tolerated in rabbits.

PURPOSE: Although eye drops are the most common form of ocular drugs, they have several limitations. Drug absorption into the eye is, in general, less than 5%, addition of preservatives is often necessary, and many drugs cannot be formulated as eye drops. Formulating ocular drugs as powder may solve these problems. The aim of this study was to investigate ocular irritation in rabbits following powder administration. METHODS: Timolol maleate (TM) powder was administered to pigmented lop rabbits. Both pure TM powder and freeze-dried with PVP-polymer (2.4% of mass) were tested in 1.0- and 0.1-mg doses. Additionally, 4 rabbits received 0.1 mg of the pure powder 3 times a day for 8 d. Redness of the bulbar conjunctiva and the amount of discharge was rated from photographs (0-3 points, randomized and masked evaluation). The 8-d experiment additionally included examination with a slit lamp and examination of hematoxylin-eosin stained sections of eyes with light microscopy. RESULTS: No serious or irreversible signs of irritation were noted. Doses of 1.0 mg were more irritating than 0.1-mg doses. There was no detectable difference in irritation between pure or freeze-dried powder. Slit-lamp examination, surface photographs and histology showed a negligible difference between drug and control eyes following the 8-d experiment. CONCLUSIONS: The results suggest that 0.1 mg of timolol powder does not irritate the eye and that testing topical timolol powder in humans is feasible.