Demeclocycline Hydrochloride

In previous studies, some tetracycline (TC) antibiotics showed potential as analgesic. We investigated here the analgesic activity of new non-antibiotic TC derivatives using the formalin-induced nociceptive pain model in adult C57BL/6 mice. Specifically, we tested the effects of i.p. injections of DDMC (5, 10, 20 mg kg^-1) and DDOX (10, 20, 40 mg kg^-1), which are non-antibiotic derivatives of demeclocycline and doxycycline, respectively. Repeated treatments with DDMC remarkably reduced nociceptive pain in both phases of the test, at 10 mg kg^-1 its efficacy was comparable to that of 10 mg kg^-1 of morphine. DDOX was also effective in this paradigm but intrinsically less potent than DDMC, exerting analgesic effects between 20 and 40 mg kg^-1. Interestingly, a single injection of DDMC (10 mg kg^-1) was sufficient to produce a robust anti-nociceptive effect similar to that of morphine. A single injection of DDOX (40 mg kg^-1) also produced anti-nociceptive effects but only in the second phase of the test. Noticeably, male mice exhibited a better analgesic response to DDMC (10 mg kg^-1) than females. A single injection of DDMC (10 mg kg^-1) and morphine but not of DDOX (40 mg kg^-1), powerfully inhibited formalin-induced spinal cord c-Fos expression whereas both TC derivatives restrained the activation of Iba-1-immunoreactive cells, indicating a potential indirect effect on inflamed microglial cells. In summary, the non-antibiotic TCs, DDMC and DDOX, demonstrated notable analgesic efficacy against formalin-induced pain, suggesting their potential as alternatives for analgesic treatment.

Establishing zonal tendon‐to‐bone attachment could accelerate the anterior cruciate ligament reconstruction (ACLR) rehabilitation schedule and facilitate an earlier return to sports. KI24RGDS is a self‐assembling peptide hydrogel scaffold (SAPS) with the RGDS amino acid sequence. This study aimed to elucidate the therapeutic potential of KI24RGDS in facilitating zonal tendon‐to‐bone attachment after ACLR.

Sixty‐four C57BL/6 mice were divided into the ACLR + SAPS and ACLR groups. ACLR was performed using the tail tendon. To assess the maturation of tendon‐to‐bone attachment, we quantified the area of mineralized fibrocartilage (MFC) in the tendon graft with demeclocycline. Immunofluorescence staining of α‐smooth muscle actin (α‐SMA) was performed to evaluate progenitor cell proliferation. The strength of tendon‐to‐bone attachment was evaluated using a pull‐out test.

The MFC and maximum failure load in the ACLR + SAPS group were remarkably higher than in the ACLR group on Day 14. However, no significant difference was observed between the two groups on Day 28. The number of α‐SMA‐positive cells in the tendon graft was highest on Day 7 after ACLR in both the groups and was significantly higher in the ACLR + SAPS group than in the ACLR group.

This study highlighted the latent healing potential of KI24RGDS in facilitating early‐stage zonal attachment of tendon grafts and bone tunnels post‐ACLR. These findings may expedite rehabilitation protocols and shorten the timeline for returning to sports.

Not applicable.