Actinomycosis is a chronic granulomatous suppurative infection caused by anaerobic bacteria from genus Actinomyces which are normal flora of mouth, colon and vagina. Actinomycosis of upper extremity is rare. We report a case of actinomycosis of the distal phalanx of finger many years after flap reconstruction. The patient presented with two months' history of chronic discharging sinus from the tip of his right index finger, which had sustained a degloving injury 20 years previously. It had been treated with an anterior chest wall flap which had healed uneventfully but was bulky due to excess tissue from the donor site. Radiograph revealed osetomyelitis changes of distal phalanx. Debulking surgery with curettage of the distal phalanx was done. Wound healing was uneventful. He was treated with six weeks of metronidazole and ciprofloxacin. The discharge from the distal phalanx cultured actinomycosis odontolyticus. Histopathology of the debrided tissue showed chronic inflammation. As far as we are aware, there are no reports of actinomycosis in a flap involving the finger treated previously with a chest wall skin flap. The infection was probably dormant for many years before manifesting as a discharging sinus. Although the finger flap was bulky, it was not problematic until it started to have serous discharge. With a thorough debridement of all infected tissue, six weeks of antibiotic was adequate. Ciprofloxacin was prescribed based on discharge culture sensitivity. Metronidazole was added as actinomycosis is anaerobic. Response was prompt as patient was not immunocompromised. At follow-up six months post-surgery the finger had recovered with good function. If not for the discharging sinus, patient would probably have tolerated his bulky finger for the rest of his life.
Exploiting natural resources for bioactive compounds is an attractive drug discovery strategy in search for new anti-malarial drugs with novel modes of action. Initial screening efforts in our laboratory revealed two preparations of soil-derived actinomycetes (H11809 and FH025) with potent anti-malarial activities. Both crude extracts showed glycogen synthase kinase 3β (GSK3β)-inhibitory activities in a yeast-based kinase assay. We have previously shown that the GSK3 inhibitor, lithium chloride (LiCl), was able to suppress parasitaemia development in a rodent model of malarial infection. The present study aims to evaluate whether anti-malarial activities of H11809 and FH025 involve the inhibition of GSK3β. The acetone crude extracts of H11809 and FH025 each exerted strong inhibition on the growth of Plasmodium falciparum 3D7 in vitro with 50% inhibitory concentration (IC50) values of 0.57 ± 0.09 and 1.28 ± 0.11 µg/mL, respectively. The tested extracts exhibited Selectivity Index (SI) values exceeding 10 for the 3D7 strain. Both H11809 and FH025 showed dosage-dependent chemo-suppressive activities in vivo and improved animal survivability compared to non-treated infected mice. Western analysis revealed increased phosphorylation of serine (Ser 9) GSK3β (by 6.79 to 6.83-fold) in liver samples from infected mice treated with H11809 or FH025 compared to samples from non-infected or non-treated infected mice. A compound already identified in H11809 (data not shown), dibutyl phthalate (DBP) showed active anti-plasmodial activity against 3D7 (IC50 4.87 ± 1.26 µg/mL which is equivalent to 17.50 µM) and good chemo-suppressive activity in vivo (60.80% chemo-suppression at 300 mg/kg body weight [bw] dosage). DBP administration also resulted in increased phosphorylation of Ser 9 GSK3β compared to controls. Findings from the present study demonstrate that the potent anti-malarial activities of H11809 and FH025 were mediated via inhibition of host GSK3β. In addition, our study suggests that DBP is in part the bioactive component contributing to the anti-malarial activity displayed by H11809 acting through the inhibition of GSK3β.
Mucosal presentation of Actinomyces viscosus results in antigen-specific systemic immune suppression, known as oral tolerance. The aim of the present study was to determine the mechanism by which this oral tolerance is induced. DBA/2 mice were gastrically immunized with A. viscosus. Serum, Peyer's patch (PP) and spleen cells were transferred to syngeneic recipients which were then systemically challenged with the sameiA. viscosus strain. To determine antigen-specificity of cells from gastrically immunized mice, recipients which received immune spleen cells were also challenged with Porphyromonas gingivalis. One week after the last systemic challenge, the delayed type hypersensitivity (DTH) response was determined by footpad swelling and the level of serum IgG, IgA and IgM antibodies to A. viscosus or P. gingivalis measured by an ELISA. No suppression of DTH response or of specific serum antibodies was found in recipients which received serum from gastrically immunized mice. Systemic immune suppression to A. viscosus was observed in recipients which had been transferred with PP cells obtained 2 days but not 4 and 6 days after gastric immunization with A. viscosus. Conversely, suppressed immune response could be seen in recipients transferred with spleen cells obtained 6 days after gastric immunization. The immune response to P. gingivalis remained unaltered in mice transferred with A. viscosus-gastrically immunized cells. The results of the present study suggest that oral tolerance induced by A. viscosus may be mediated by antigen-specific suppressor cells which originate in the PP and then migrate to the spleen.