Carpal tunnel syndrome (CTS) and trigger finger are known to occur together in association with conditions such as diabetes mellitus, rheumatoid arthritis and hypothyroidism. Although most cases that present to a hand clinic have no obvious predisposing cause, the two conditions often appear together in the same patient. We performed a prospective study of the prevalence of CTS in hospital outpatients presenting with trigger finger. Six hundred and eighty-one patients with CTS, trigger finger or both conditions were recruited prospectively. Diagnosis of both disorders was made on clinical grounds. The study group comprised 551 patients with no obvious predisposing cause. Of 211 patients with trigger finger, 91 (43%) also had CTS. This prevalence is substantially higher than the population prevalence of CTS of approximately 4%. Our data support an association between idiopathic CTS and idiopathic trigger finger and lend support to common pathophysiological factors.
Inspired by the well-documented tumor protecting ability of paullones, recently, we synthesized novel paullone-like scaffolds, indole-fused benzo-oxazepines (IFBOs), and screened them against hepatocellular carcinoma (HCC) specific Hep-G2 cells. Three of the synthesized compounds significantly attenuated the progression of HCC in vitro. By computational studies, we further discovered that IFBOs exhibited a stable binding complex with the IL-6 receptor. In this context, we investigated in vivo study using the nitrosodiethyl amine (NDEA)-induced HCC model, which strengthened our previous findings by showing the blockade of the IL-6 mediated JAK2/STAT3 oncogenic signaling pathway. Treatment with IFBOs showed remarkable attenuation of cellular proliferation, as evidenced through a decrease in the number of nodules, restoration of body weight, oxidative stress parameters, liver marker enzymes and histological architecture. Interestingly, using a metabolomic approach we further discovered that IFBOs can restore the perturbed metabolic profile associated with the HCC condition to normalcy. Particularly, the efficacy of compound 6a for an anti-HCC response was significantly better than the marketed chemotherapeutic drug, 5-fluorouracil. Altogether, these remarkable findings open up possibilities of developing IFBOs as novel future candidate molecules for plausible alternatives for HCC treatment.
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