Atorvastatin liposomes in a 3D-printed polymer film: a repurposing approach for local treatment of oral candidiasis.

Oral candidiasis (OC) is an opportunistic fungal infection, common amongst the elderly and the immunocompromised. Unfortunately, the therapeutic efficacy of common antifungals is imperiled by the rise of antifungal drug resistance. An alternative promising therapeutic option possibly contributing to antifungal therapy is drug repurposing. Herein, we aimed to employ novel pharmaceutical drug delivery for enhancing the emerging antifungal potential of the hypocholesterolemic drug atorvastatin (ATV). ATV-propylene-glycol-liposomes (ATV/PG-Lip) were prepared then integrated in 3D-printed (3DP) mucoadhesive films comprising chitosan, polyvinyl-alcohol and hydroxypropyl methylcellulose, as an innovative blend, for the management of OC. ATV/PG-Lip demonstrated good colloidal properties of particle size (223.3 ± 2.1 nm), PDI (0.12 ± 0.001) and zeta potential (-18.2 ± 0.3 mV) with high entrapment efficiency (81.15 ± 1.88%) and sustained drug release. Also, ATV/PG-Lip showed acceptable three-month colloidal stability and in vitro cytocompatibility on human gingival fibroblasts. The developed 3DP-films exhibited controlled ATV release (79.4 ± 1.4% over 24 h), reasonable swelling and mucoadhesion (2388.4 ± 18.4 dyne/cm2). In vitro antifungal activity of ATV/PG-Lip was confirmed against fluconazole-resistant Candida albicans via minimum inhibitory concentration determination, time-dependent antifungal activity, agar diffusion and scanning electron microscopy. Further, ATV/PG-Lip@3DP-film exceeded ATV@3DP-film in amelioration of infection and associated inflammation in an in vivo oral candidiasis rabbit model. Accordingly, the results confirm the superiority of the fabricated ATV/PG-Lip@3DP-film for the management of oral candidiasis and tackling antifungal resistance.

Evaluation of the Effect of Duration on the Efficacy of Pulsed Radiofrequency in an Animal Model of Neuropathic Pain.

BACKGROUND: Pulsed radiofrequency (PRF) is increasingly used in clinical practice, especially in neuropathic pain disorders. Although PRF is not new to clinical use, there are significant gaps in knowledge regarding its effectiveness. OBJECTIVES: The current study was conducted to evaluate the effect of duration of application of PRF on its analgesic efficacy in improvement of neuropathic pain. STUDY DESIGN: A randomized experimental trial. SETTING: An animal research facility at the College of Veterinary Medicine at Mansoura University in Egypt. METHODS: Chronic constriction of the sciatic nerve of 36 male Sprague-Dawley rats was performed to induce neuropathic pain. The rats were divided into 6 groups (6 rats each) in which PRF was applied for 2, 4, 6, or 8 minutes or not at all. In one group, RF cannula was applied without performing PRF intervention. The pain was assessed through observation of resting paw posture (RPP) at 3, 10, and 21 days. Nerve damage was assessed by histopathological evaluation of the sciatic nerve. Immunohistochemical localization of proinflammatory cytokines (interleukin 6 [IL-6] and tumor necrosis factor alpha [TNF-alpha]) was also done. RESULTS: RPP was improved in rats treated with PRF. This improvement was significant only in rats treated for 8 minutes. Increased duration for PRF application was associated with a significant decrease in IL-6 and TNF-alpha contents in all groups when compared with the control group. Histopathological evaluation of the constricted sciatic nerve revealed no statistical significance among the different study groups. LIMITATIONS: The study was limited by the lack of measurement of other inflammatory markers that may help elucidate other relevant mechanisms. CONCLUSIONS: Increased duration of PRF application resulted in better analgesic efficacy without any increase in tissue injury in an animal model of neuropathic pain. This effect may be attributed to decreased production of pro-inflammatory cytokines. KEY WORDS: Pulsed radiofrequency, analgesic, rats, sciatic nerve, duration, neuropathic pain.

Renoprotection against complete unilateral ureteric obstruction: Is there an ultimate choice?

OBJECTIVES: To evaluate and compare the relative contribution of different therapeutic agents for renoprotection against complete unilateral ureteric obstruction (UUO), using a rabbit model sampled at different times. MATERIALS AND METHODS: Eighty-four male New Zealand White rabbits were divided into seven groups of 12 rabbits; a sham group, a control (left UUO + no medication) or left UUO and treated with either enalapril, losartan, verapamil, l-arginine or antioxidant (vitamin E and selenium mixture). Rabbits in the control and treated groups were subjected to 3, 10 and 21 days of complete ureteric ligation and then killed humanely. The control and treated groups were evaluated at baseline and at the end of the experiment, by measuring split effective renal plasma flow (ERPF) using diuretic renography, and the split glomerular filtration rate (GFR) using selective creatinine clearance. Renal histopathology was evaluated using a tubulo-interstitial damage score. RESULTS: In the sham group there was no significant effect on any of the evaluated variables. For split ERPF, losartan showed the highest renoprotective effect, saving 44% and 77% of ERPF at 3 and 21 days after UUO, respectively. Losartan was also the best renoprotective agent for GFR. For renal histopathology, enalapril showed the earliest and greatest improvement as assessed by the damage score, reaching 60% at 21 days after UUO. l-Arginine was the next best effect to blockade the renin-angiotensin system for renoprotection. CONCLUSION: We suggest that blockade of the renin-angiotensin system provides the best renoprotection against the effects of complete UUO.

Use of oxidized cellulose for corporal body grafting and suture-less correction of severe penile chordee: an experimental study in rabbits.

OBJECTIVE: To evaluate the efficacy of oxidized cellulose, Surgicel(TM) (Johnson & Johnson Medical, New Brunswick, NJ, USA) for patching defects in the tunica albuginea in a rabbit model, with a future application to correct chordee. MATERIALS AND METHODS: The study comprised nine New Zealand white male rabbits; a rectangular 15 x 5-mm defect was created in the ventral tunica albuginea that was covered by Surgicel. The skin was closed with no catheters left in situ after the procedure. The rabbits were killed in groups of three at 2, 6 and 12 weeks after surgery. The evaluation included cavernosography and histopathological examination of sections of the penis stained with haematoxylin and eosin, and Masson's trichrome. RESULTS: No deaths were caused by the procedure, and none of the rabbits developed bleeding or haematoma after surgery. Cavernosography at 2 weeks showed contrast medium leaking from the site of the Surgicel, but at 6 and 12 weeks all rabbits had a straight erection with patent corpora and no evidence of narrowing or venous leak. Histopathological evaluation revealed evidence of the remnants of Surgicel surrounded by acute inflammatory cell infiltrate with early neovascularization at 2 weeks. At 6 and 12 weeks, there was complete normal regeneration of the tunica albuginea with no foreign-body reaction. CONCLUSIONS: In this pilot study, Surgicel had a clear haemostatic effect when covering a defect in the tunica albuginea. Moreover, normal tunica albuginea regenerated by 6 weeks and was maintained at 12 weeks. These results suggest that Surgicel might be considered a safe and effective grafting material for tunica albuginea substitution, including the surgical management of penile chordee.

Use of single layer small intestinal submucosa for long segment ureteral replacement: a pilot study.

PURPOSE: Previous studies have demonstrated successful use of small intestinal submucosa (SIS) as a tube for replacing short segment (11 mm) proximal ureteral defects. However, such small segment ureteral defects could be managed by resection re-anastomosis. We evaluated the use of 1-layer SIS as a tube for the replacement of long segment ureteral defects. MATERIALS AND METHODS: The ureters of 5 female mongrel dogs were accessed through a median laparotomy incision. A 4 cm segment of mid ureter was resected on the right side. The right ureteral segments were replaced by tubularized SIS segments using 6-zero polydioxanone interrupted sutures. Internal pigtail stents were left for 6 weeks. All animals were sacrificed at 12 weeks. Ureteral patency was assessed by excretory urography and magnetic resonance urography 7 and 12 weeks after the initial procedures. Inflammation and regeneration were assessed histologically. RESULTS: At 12 weeks all ureters on the experimental side were completely occluded with significant hydroureteronephrosis and the subsequent deterioration of kidney function. At autopsy there was failure to calibrate any of the experimental ureters with a 3Fr catheter. Although histologically urothelium and muscular cells had proliferated over the graft, they were embedded in an intense fibrotic and inflammatory process. CONCLUSIONS: Technically 1-layer SIS was easily modeled, providing the conditions for watertight anastomosis. The regeneration of urothelium and muscle was induced and supported by the graft. However, functional replacement was not successful. One-layer SIS is not a suitable material for replacing long segment (4 cm) ureteral defects.