Fibrosing colonopathy associated with cysteamine bitartrate delayed-release capsules in cystinosis patients.

BACKGROUND: The objective of this report is to identify and characterize cases of fibrosing colonopathy, a rare and underrecognized adverse event, associated with cysteamine delayed-release (DR) in patients with nephropathic cystinosis. METHODS: We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the medical literature for postmarketing reports of fibrosing colonopathy associated with cysteamine through August 2, 2023. RESULTS: We identified four cases of fibrosing colonopathy reported with the use of cysteamine DR. The time to onset ranged from 12 to 31 months. In one case, the patient required surgery to have a resection of a section of the strictured colon and a diverting ileostomy. Fibrosing colonopathy was diagnosed by histopathology in two of the cases. CONCLUSIONS: Our case series identified the risk of fibrosing colonopathy in patients taking cysteamine DR and prompted regulatory action by the FDA. As outlined in changes to the U.S. prescribing information for cysteamine DR, healthcare professionals should be aware of the potential risk of fibrosing colonopathy with cysteamine DR, especially as symptoms can be non-specific leading to misdiagnosis or delayed diagnosis. If the diagnosis of fibrosing colonopathy is confirmed, consideration should be given to permanently discontinuing cysteamine DR and switching to cysteamine immediate-release treatment.

Spontaneous intramural hematoma of the alimentary canal.

Spontaneous intramural hematoma of the alimentary canal has rarely been reported. We present two cases in which anticoagulation therapy brings spontaneous intramural hematoma of the alimentary canal. In one case, the lesion was located in the ileum, and the other was located in the ascending colon and distal ileum. Both patients were cured through conservative treatment. We suggest that increased attention should be paid if a patient has acute abdominal pain with a history of oral anticoagulant therapy, and the diagnosis of spontaneous intermural hematoma should be considered.

Nonsteroidal Anti-Inflammatory Drug-Induced Colopathy in a Colorectal Cancer Screening Program.

OBJECTIVE: To present a case of colopathy related to the use of diclofenac in a patient with a positive immunochemical faecal occult blood test (iFOBT) and to discuss the influence of nonsteroidal anti-inflammatory drugs (NSAIDs) on iFOBT specificity. CLINICAL PRESENTATION AND INTERVENTION: A colonoscopy in a 56-year-old female presenting with a positive iFOBT revealed diaphragm-like strictures and ulcers in the right colon. While carrying out a detailed retrospective interview, she reported a chronic backache requiring long-term NSAID treatment. CONCLUSION: No association has been established between chronic use of NSAID and a false-positive iFOBT. There is no need to stop NSAIDs before performing an iFOBT in a colorectal cancer screening program.

Suppression of methionine-induced colon injury of young rats by cysteine and N-acetyl-L-cysteine.

Changes in the methionine metabolism can cause a state called hyperhomocysteinemia, inducing oxidative stress in the gut. The production of free radicals is important in the colon damage caused by methionine. This study aimed at evaluating the effect of the use of L-cysteine and N-acetyl-L-cysteine on the colon morphometry of young rats treated with methionine. A total number of 32 male rats were distributed in a randomized experimental design in 4 groups: control group treated with saline; methionine group; cysteine + methionine group, and N-acetyl-L-cysteine + methionine group. After 21 days of treatment, rats were sacrificed and the colon samples were taken for histological and biochemical analysis. Methionine load increased depth of crypts, the lamina muscularis mucosae thickness, the mucosal height, and the number of cells in lamina propria (p < 0.01). Combination of methionine with L-cysteine (C group) and with N-acetyl-L-cysteine (N group) reversed methionine effects. Methionine treatment increased the GPx activity and MDA concentration, while L-cysteine and N-acetyl-L-cysteine increased the catalase activity compared to methionine group. It was concluded that the use of L-cysteine and N-acetyl-L-cysteine was beneficial to decrease intestinal mucosal height and oxidative damage when methionine was used in combination with them.

Colon constipation in horses after sustained-release buprenorphine administration.

OBJECTIVE: To investigate the pharmacological profile and side effects of buprenorphine administered as a sustained-release formulation in horses. STUDY DESIGN: Pilot trial. ANIMALS: A total of four experimental horses, aged 18-27 years and weighing 508-578 kg. METHODS: Buprenorphine (0.1 mg kg-1) was mixed as a freshly prepared sterile solution with a sustained-release drug carrier. It was administered by the subcutaneous (n = 2) or intramuscular (n = 2) route. During the experiment, the horses were closely monitored, equipped with a step counter and blood samples were collected for quantification of buprenorphine in plasma. RESULTS: All four horses developed colon constipation requiring medical therapy, together with increased locomotor activity. One horse, requiring surgical treatment of colon constipation, was euthanized during recovery from anaesthesia for weakness and severe lower airway obstruction. The three other horses recovered fully within 5-7 days. Plasma buprenorphine concentrations were between 1 and 8 ng mL-1 for approximately 48 hours. No local reaction was observed at the injection sites. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of the sustained-release formulation of buprenorphine at a dose of 0.1 mg kg-1 resulted in plasma concentrations compatible with antinociceptive activity for at least 48 hours. The observed severe and undesirable effects of colon constipation and increased locomotor activity definitely preclude clinical use of sustained-release buprenorphine at this dose.

[The Drug Interaction that Psychiatrists Should be Careful about].

Drug combination therapy is sometimes used in clinical situations. CYP has been intensely studied numerous times ; thus, its pharmacokinetic interactions have been predicted to some extent. Basically, a drug interaction is defined as competitive inhibition of an enzyme by two drugs. We are concerned that fluvoxamine may have a drug interaction with paroxetine. Flu-voxamine inhibits CYPlA2 and CYP2C9 activity, and paroxetine inhibits CYP2D6 activity. However, recently, new drug targets have been identified, such as P-glycoprotein, a drug transporter. Fluvoxamine and paroxetine inhibit not only CYP but also P-glycoprotein. Additionally, there is an increased risk of upper gastrointestinal tract bleeding with the combination of a SSRI and NSAIDs. There are also individual differences in the pharmacokinetics of drugs due to genetic factors and individual differences in drug receptors, which have not yet been investigated for fluvoxamine or paroxetine. Obtaining clinical diagnoses of drug interactions is necessary in all patients.

Acupoint Specificity on Colorectal Hypersensitivity Alleviated by Acupuncture and the Correlation with the Brain-Gut Axis.

This project was focused on the study of the effect of the different acupoints on visceral hypersensitivity and the correlation with the brain-gut axis. By using a mouse model of zymosan-induced colorectal hypersensitivity, and observing the response of hypersensitivity model to colorectal distension stimulation in acupuncture at different acupoints, we selected the specific acupoints. With immunohistochemical staining method, we observed c-fos expression, distribution and changes after acupuncture on sensory pathway, including colorectum, spinal dorsal horn and different regions of brain center in the model with colorectal distension stimulation, and evaluated the acupuncture effect on brain-gut axis. The results revealed that the effectiveness of acupuncture for alleviating visceral hypersensitivity was different at individual acupoint, meaning Tianshu (ST25), Zusanli (ST36) and Shangjuxu (ST37) > Quchi (LI11) and Dachangshu (BL25) > Ciliao (BL32). C-fos expression was concentrated in anterior cingulate cortex, hypothalamus, spinal dorsal horn and colorectum in model of zymosan-induced colorectal hypersensitivity and it was down-regulated after acupuncture. The results demonstrates that the acupoint specificity presents in acupuncture for relieving visceral hypersensitivity and the effects are more predominated at the acupoints on stomach meridian innervated by the same or adjacent spinal ganglion segments. The model of zymosan-induced colorectal hypersensitivity can be the animal model simulating brain-gut interaction.

[Colonic ulcers associated with taking Kayexalate(®) (sodium polystyrene sulfonate): about two cases]. / Ulcérations coliques associées à la prise de Kayexalate(®) (polystyrène sulfonate de sodium) : à propos de deux observations.

We report two cases of patients with chronic renal failure showing rectal bleeding due to digestive ulcers, associated with Kayexalate(®) alone. Kayexalate(®) crystals correspond to a typical histological picture and it is important to know how to identify them in order to discuss a possible pathogenicity.

Can liquorice extract and herbal solution prevent colonic mucosa damage caused by robenacoxib in dogs?

UNLABELLED: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in animals, especially in dogs, to manage pain due to inflammatory disease. This study investigated whether plant drugs can prevent mucosal injury induced by robenacoxib. We used fifteen healthy beagle dogs (7 male and 8 female) aged 4 months, weighing 4.2-5.1 kg at the beginning of the study. Endoscopy and biopsy of the colon were performed before and on the 21 day treatment with robenacoxib (1), robenacoxib, herbal solution with liquorice extract (2), placebo - an empty capsule (3). There were 5 animals in each group. The greatest microscopic damage in the colon was observed in animals which received robenacoxib. Plant drug administration reduced the severity of lesions in the colon when administered with robenacoxib (ARI = - 0.15). CONCLUSION: concurrent administration of liquorice extract and plant solution with robenacoxib was associated with significant decreased severity of the robenacoxib-induced colonic mucosal lesions.

Colonic inflammation and secondary bile acids in alcoholic cirrhosis.

Alcohol abuse with/without cirrhosis is associated with an impaired gut barrier and inflammation. Gut microbiota can transform primary bile acids (BA) to secondary BAs, which can adversely impact the gut barrier. The purpose of this study was to define the effect of active alcohol intake on fecal BA levels and ileal and colonic inflammation in cirrhosis. Five age-matched groups {two noncirrhotic (control and drinkers) and three cirrhotic [nondrinkers/nonalcoholics (NAlc), abstinent alcoholic for >3 mo (AbsAlc), currently drinking (CurrAlc)]} were included. Fecal and serum BA analysis, serum endotoxin, and stool microbiota using pyrosequencing were performed. A subgroup of controls, NAlc, and CurrAlc underwent ileal and sigmoid colonic biopsies on which mRNA expression of TNF-α, IL-1ß, IL-6, and cyclooxygenase-2 (Cox-2) were performed. One hundred three patients (19 healthy, 6 noncirrhotic drinkers, 10 CurrAlc, 38 AbsAlc, and 30 NAlc, age 56 yr, median MELD: 10.5) were included. Five each of healthy, CurrAlc, and NAlc underwent ileal/colonic biopsies. Endotoxin, serum-conjugated DCA and stool total BAs, and secondary-to-primary BA ratios were highest in current drinkers. On biopsies, a significantly higher mRNA expression of TNF-α, IL-1ß, IL-6, and Cox-2 in colon but not ileum was seen in CurrAlc compared with NAlc and controls. Active alcohol use in cirrhosis is associated with a significant increase in the secondary BA formation compared with abstinent alcoholic cirrhotics and nonalcoholic cirrhotics. This increase in secondary BAs is associated with a significant increase in expression of inflammatory cytokines in colonic mucosa but not ileal mucosa, which may contribute to alcohol-induced gut barrier injury.

Hydroxyurea and colonic ulcers: a case report.

BACKGROUND: Hydroxyurea at a relatively low dose is frequently prescribed to induce hemoglobin F production in patients with sickle cell and ß-thalassemia diseases because of its good efficacy and safety profiles. However, a potentially fatal gastrointestinal ulceration was recently found and herein reported. CASE PRESENTATION: A thirty-seven-year-old man with transfusion dependent hemoglobin E/ß-thalassemia disease was treated with hydroxyurea to induce hemoglobin F production since 2007 without incident. From 2008 to April 2010, episodes of hematochezia, mucous diarrhea and epigastric pain intermittently manifested. Four colonoscopies done during the period repeatedly showed ulcerative lesions from the terminal ileum to the ascending colon with a non-specific histo-pathologic finding. Subsequently, ulcerative lesions also developed at the pharynx, histo-pathologic findings of which were not different from those in the colon. These ulcerative lesions resolved within a month after discontinuing hydroxyurea in April 2010 and have not recurred since. CONCLUSION: The findings suggested role of hydroxyurea in the pathogenesis of these ulcers, and that it must be immediately discontinued to prevent further damage to the digestive mucosa.