Impaired or blunted rectal sensation, termed rectal hyposensitivity (RH), which is defined clinically as elevated sensory thresholds to rectal balloon distension, is associated with disorders of hindgut function, characterised primarily by symptoms of constipation and fecal incontinence. However, its role in symptom generation and the pathogenetic mechanisms underlying the sensory dysfunction remain incompletely understood, although there is evidence that RH may be due to 'primary' disruption of the afferent pathway, 'secondary' to abnormal rectal biomechanics, or to both. Nevertheless, correction of RH by various interventions (behavioural, neuromodulation, surgical) is associated with, and may be responsible for, symptomatic improvement. This review provides a contemporary overview of RH, focusing on diagnosis, clinical associations, pathophysiology, and treatment paradigms.
Afferent Pathways ; Biomechanics ; Constipation ; Fecal Incontinence ; Sensation ; Sensory Thresholds

Background: Infection with Mycobacterium tuberculosis, the causative agent of TB, is responsible for one of the global epidemics. Thus, new drugs are needed that do not confer cross-resistance with currently administered front-line therapeutics. Quinoline-based natural products and synthetic derivatives have been extensively explored for antitubercular activity.
Objective: The main goal of this study was to prepare a collection of benzylated 8-hydroxyquinoline derivatives through synthesis and assess their antitubercular activity along with a molecular docking study to clarify their biological mechanism of action.
Methodology: The benzylated 8-hydroxyquinoline derivatives were synthesized using Williamson synthesis methods. Antitubercular activity was assessed against fast replicating M. tuberculosis H??Rv using Microplate Alamar Blue Assay (MABA) and non-replicating cultures using Low-Oxygen Recovery Assay (LORA). Molecular docking studies were carried out against enoyl-acyl carrier protein reductase (InhA).
Results: Five benzylated 8-hydroxyquinoline derivatives were synthesized in moderate yields and characterized using NMR spectroscopy. MABA and LORA assays indicate compounds 3-5 as the most inhibitory derivatives with MIC90's ranging from 6.38 to 54.28 ?M. Molecular docking against InhA showed modest 90 binding energies for compounds 4 (-8.5 kcal/mol) and 5 (-8.6 kcal/mol).
Conclusion: Findings suggest a rationale for the further evolution of this promising series of antitubercular quinoline small molecules. Structure-activity analysis shows that an 8-benzyl moiety with chlorine atom/s is important for improved activity against replicating and non-replicating M. tb. H??Rv. This is also supported by our in silico studies.

Mycobacterium tuberculosis ; Quinolines ; Molecular Docking Simulation