Novel fibro-inflammatory biomarkers associated with disease activity in patients with Crohn's disease.

INTRODUCTION: Crohn's disease (CD) is a complex disease, and assessing activity is challenging due to pathobiologic process e.g. ECM remodeling, mucosal damage, and intestinal fibrosis, which greatly limits current disease activity assessments through e.g. endoscopy and imaging techniques. AREAS COVERED: The review highlights the importance of novel biomarkers reflecting ECM remodeling and immune cell activity that accurately reflect CD activity and progression. Such biomarkers could include collagen formation and degradation fragments and a serum fragment of calprotectin, reflecting neutrophil activity. A new concept, fibro-inflammation, is also introduced in the review, in which all aspects of mucosal damage, such as inflammation, mucosal damage, tissue remodeling, intestinal fibrosis, and fibrosis resolution, should be assessed. PubMed searches performed from July 2022 - November 2022 provided the scientific information included in the review. EXPERT OPINION: Current data suggest intestinal fibrosis may sustain and exacerbate chronic inflammation, leading to non-response to anti-inflammatory treatments. Therefore, evaluating novel biomarkers reflecting different stages of fibro-inflammatory disease activity should be done in a clinical setting and considered for clinical trials. This approach will help accurately assess disease activity, leading to better management and treatment of CD.

Cardiac rhabdomyoma presenting as left ventricular outflow tract obstruction in a neonate.

A case of congenital cardiac rhabdomyoma presenting as left ventricular outflow tract obstruction is reported. Congenital cardiac tumours are rare. Rhabdomyomas are the most common. Fifty-one to 86% of them are associated with tuberous sclerosis. They have a tendency for spontaneous regression. The indications for surgery include haemodynamic compromise and intractable arrhythmias.

Solution-phase, parallel synthesis and pharmacological evaluation of acylguanidine derivatives as potential sodium channel blockers.

Solution-phase synthesis of various acylguanidine derivatives and the evaluation of a small library of compounds as potential sodium channel blockers are described.

Design and synthesis of sialyl Lewis x mimics as E-selectin inhibitors.

The design and synthesis of novel beta-C-mannosides that inhibit the binding of sialyl Lewis x to E-selectin are described. Compounds that contained a phenyl substituent at the C-6 position were found to have increased potency.

Glibenclamide antagonizes the inhibitory effect of morphine on gall bladder emptying.

Egg yolk-induced gall-bladder emptying in mice was used to investigate the effect of glibenclamide and minoxidil (ATP-dependent K(+)-channel modulators) on biliary tract effects of morphine. The inhibitory effect of morphine (1-4 mg kg-1, i.p.) on egg yolk-induced gall-bladder emptying was completely blocked by pretreatment with naloxone (2 mg kg-1, i.p.) or glibenclamide (0.65 mg kg-1, i.p.) whereas, pretreatment with minoxidil (0.65 mg kg-1, i.p.) did not modify the inhibitory effect of morphine on gall-bladder emptying. Our results suggest that biliary-tract actions of morphine are mediated through glibenclamide-sensitive K+ channels similar to those involved in the analgesic action of morphine.

Becker muscular dystrophy: an unusual presentation.

A 15 year old boy who presented with passing painless dark urine was found to have myoglobinuria. His creatine phosphokinase was raised, and a muscle biopsy specimen showed non-specific dystrophic changes. Subsequent DNA analysis led to the diagnosis of Becker muscular dystrophy. Myoglobinuria may be a presenting symptom of Becker muscular dystrophy.

Immunological and clinical consequences of vasectomy.

Blood samples from 109 vasectomized and 100 non-vasectomized fertile men were tested for antisperm antibodies using Tray Agglutination Test (TAT) and Sperm Immobilization Test (SIT), Cell Mediated Immunity to sperm using Leukocyte Migration Inhibition Test (LMIT). Incidence of antisperm antibodies in vasectomized group was 76.2% by TAT and 13.8% by SIT whereas in control group was 11% (p less than 0.001) and 3% (P less than 0.01) respectively. Titre of TAT antibodies increased with post vasectomy period even beyond 20 years post vasectomy. High Incidence of TAT titre of greater than 1:250 was observed in vasectomized men with post operative complications. No significant incidence of positive LMIT to sperm antigens was detected in vasectomized group as compared to control group.

PIP: This study examined the long-term effects of vasectomy on humoral antibody responses detected by the Tray Agglutination Test (TAT) and the Microsperm immobilization test (SIT) as well as the Leukocyte Migration Inhibition Test (LMIT). Immunological results are compared with postvasectomy complications in a total of 109 men between ages 30-60. These results were compared with 100 nonvasectomized fertile controls. Procedures for each of the tests conducted are described. The incidence of TAT and SIT antibodies in the vasectomized group is significantly higher (P0.001 and P0.01) than in the control group. The incidence of agglutinating antibodies rises to about 60% by 4 years postvasectomy and reaches a plateau of 76% in 6-8 years; the sperm immobilizing antibody rises steadily as the postvasectomy period lengthens. There was no statistically significant difference in the incidence of positive LMIT and leukocyte migration inhibition index between the 2 groups. Of the 4 subjects who developed local infection postoperatively, 2 had a high sperm agglutination titer of 1:256. High antibody titer was also seen in 5 of 7 subjects who developed swelling at the ligation site. The results in this study yielded and 11% incidence of sperm agglutinating antibodies in nonvasectomized fertile males. 62% of those who had vasectomies developed these antibodies within the 1st few years. This indicates that the majority of vasectomized men are early responders to sperm antigens. This study also revealed that sperm immobilizing antibodies rise as the postvasectomy period lengthens, even beyond 20 years. Thus, 83 of 109 vasectomized subjects developed these sperm agglutinating antibodies and only 13 of 50 subjects who had an antibody titer of 1:250 developed postoperative complications. Vasectomy does not lead to cell-mediated immunity to spermatozoal antigens.