Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cholic Acid (MT921) after a Subcutaneous Injection in the Submental Area to Humans.

This study aimed to explore pharmacokinetics, pharmacodynamics, and safety/tolerability of MT921, an injectable cholic acid, after a single subcutaneous administration to healthy volunteers. A randomized, double-blinded, placebo-controlled, single dose-ascending phase 1 study enrolled 24 subjects who were assigned to three groups (60 mg, 120 mg, and 150 mg) of MT921. Blood samples were obtained for a 24-h period before and after injecting MT921 to the submental fat area. Plasma concentrations of cholic acid and deoxycholic acid were determined for pharmacokinetic analysis. Levels of free fatty acid, triglyceride, and total cholesterol were measured for pharmacodynamic analysis. Safety and tolerability were assessed until 21 days post-dose. While systemic exposure to cholic acid tended to increase as the MT921 dose increased, pharmacokinetic profiles of deoxycholic acid were similar among dose groups without showing significant changes. Pharmacodynamic profiles were comparable when measured at baseline and post-dose. The most frequent adverse events were injection site pain and edema. All adverse drug reactions resolved without treatment. MT921 appeared to be well-tolerated after an injection to the submental area at a dose up to 150 mg. Systemic exposure to cholic acid increased as the dose increased. Blood lipid profiles and deoxycholic acid levels were not affected by MT921 treatment.

Electrochemical treatment of ex vivo human abdominal skin and potential use in scar management: A pilot study.

INTRODUCTION: Scar treatments aim to address pathologic collagen deposition; however, they can be expensive or difficult to control. Electrochemical therapy (ECT) offers a simple alternative treatment. The purpose of this study is to examine the acid-base and histological changes in ex vivo human abdominal skin following ECT. METHODS: Forty-two ex vivo human panniculus tissue sections collected from six individuals were tumesced with normal saline. ECT was performed by inserting two platinum needle electrodes connected to a DC power supply into each specimen. Voltage was varied (3-6 V) and applied for 5 minutes. Each specimen was sectioned across both electrode insertion sites and immediately stained with pH sensitive dye. The width of dye color change for each dosimetry pair was calculated. Hematoxylin and eosin staining was used to evaluate samples. RESULTS AND DISCUSSION: ECT caused a spatially localised and dose-dependent increased area of acidic and basic pH around the anode and cathode, respectively. A significantly greater mean width of pH change was generated at the cathode compared to the anode in all treatment groups. Histological evaluation displayed broad condensation and hyalinisation of dermal collagen. CONCLUSION: ECT triggered dermal pH alterations and changed the underlying structural framework of the specimen. This technology may serve as a low-cost, minimally invasive local soft-tissue remodeling technique with potential application in scar management. LEVEL OF EVIDENCE: 5. LAY SUMMARY: Electrochemical therapy is a novel treatment that causes spatially selective dermal injury in areas of interest. This study measures the effects of electrochemical therapy when applied to abdominal skin. Electrochemical therapy appears to have beneficial effects by causing a highly localised reduction in collagen content or local softening of tissue, which is consistent with other studies on scar therapies, including chemexfoliation, radiofrequency technologies, and lasers. However, electrochemical therapy can be performed at a fraction of the costs of these aforementioned modalities.

Electrochemical Therapy of In Vivo Rabbit Cutaneous Tissue.

OBJECTIVES: To examine the acid-base and histological changes in in vivo rabbit cutaneous tissue after electrochemical therapy. STUDY DESIGN: In vivo rabbit tissue study. METHODS: The shaved skin on the backs of female Oryctolagus cuniculi were assigned to treatments with or without tumescence with normal saline. Two platinum-needle electrodes were inserted into each treatment area and connected to a direct current (DC) power supply. Voltage (3-5 V) was varied and applied for 5 minutes. The wound-healing process was monitored via digital photography and ultrasonography until euthanasia at day 29. Treatment areas were biopsied, and specimens were sectioned through a sagittal midline across both electrode insertion sites. Samples were then evaluated utilizing light microscopy (hematoxylin and eosin, Masson's Trichrome, and Picrosirius red). RESULTS: Treatment sites developed mild inflammation that dissipated at lower voltages or became scabs at higher voltages. Ultrasonography demonstrated acoustic shadowing with spatial spread that increased with increasing voltage application. The 4- and 5-V sites treated with saline had localized areas of increased tissue density at day 29. Although specimens treated with 3 V did not look significantly different from control tissue, 4- and 5-V samples with and without saline tumescence had finer, less-organized collagen fibers and increased presence of fibrocytes and inflammatory infiltrates. CONCLUSIONS: Electrochemical therapy caused localized injury to in vivo rabbit cutaneous tissue, prompting regenerative wound repair. With future development, this technology may offer precise, low-cost rejuvenation to restore the functionality and appearance of dermal scars and keloids. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E2196-E2203, 2021.

Electrochemolipolysis of Human Adipose Tissue.

Importance: Body fat contouring procedures have increasingly grown in popularity over the years. As such, there is a need for inexpensive, minimally invasive, and simple fat reduction/contouring technique. Objective: To examine the acid-base and histological changes in ex vivo human adipose tissue after electrochemolipolysis (ECL). Design, Setting, and Participants: Panniculus tissue specimens obtained after abdominoplasty procedures were tumesced with normal saline. Two platinum needle electrodes were inserted into each sample and connected to a DC power supply. Voltage (3-6 V) was varied and applied for 5 min. Specimens were sectioned through a sagittal midline across both electrode insertion sites and immediately stained with pH-sensitive dye. A numerical algorithm was used to calculate the area of the dye color change for each dosimetry pair. Samples were also evaluated utilizing light microscopy (hematoxylin and eosin). An ex vivo human adipose tissue model was used for evaluating the effects of ECL. Results: Acidic and basic pH was appreciated surrounding the anode and cathode insertion sites, respectively. The effect was spatially localized and dose dependent. Statistical analysis of these data showed no significant difference between the mean area of the pH disturbance generated at the anode compared with the cathode at 3 V for 5 min (6.04 mm2 vs. 2.95 mm2, p = 0.40, 95% CI -4.8 to 11). A significantly greater area of pH disruption was generated at the cathode versus the anode in groups 4 V for 5 min (14.7 mm2 vs. 5.00 mm2, p = 0.032, 95% CI 0.93-19), 5 V for 5 min (15.5 mm2 vs. 6.72 mm2, p = 0.019, 95% CI 1.6-16), and 6 V for 5 min (22.5 mm2 vs. 10.0 mm2, p = 0.047, 95% CI 0.22-25). Acute structural changes in adipocytes were observed in all specimens. Vascular damage with adjacent adipocyte necrosis was prominent at the cathode site in group 6 V for 5 min. Conclusions and Relevance: ECL at the studied dosimetry parameters induced acid and base changes in human adipose tissue, suggesting its potential use in nonsurgical fat reduction as an ultralow cost alternative to current lipolytic devices and pharmaceuticals. Level of Evidence: NA.

Round excisions lead to shorter scars and better scar positioning than traditional elliptical excisions.

BACKGROUND: As traditional elliptical excisions for skin tumors are designed before surgery, they may waste normal tissue and result in poor outcome, both in terms of the wound length and direction. OBJECTIVE: To compare the predicted results of elliptical excisions with scars resulting from round excisions with dog ear repairs. METHODS: Forty-one patients with skin tumors were prospectively studied. Each lesion was examined and an optimal ellipse was designed and marked on the skin. Only the lesion and the required margin of adjacent skin were excised and closed with dog ear repairs. Precise measurements were conducted at each step. RESULTS: Although many of the lesions required 2 dog ear repairs (59%), the overall sutured wound length was 14% shorter, and the wound direction differed from that of the predicted ellipse in 22% of cases. The shortening effect was distinctive in areas of thick skin, such as the trunk and scalp. Only 3 lesions resulted in a longer final wound length. In total, 29% of the patients required 1 dog ear repair and 12% needed no dog ear repairs. CONCLUSION: Round excisions with dog ear repairs should be considered prior to traditional elliptical excision as a more beneficial method of skin tumor removal.

Cryptococcal meningitis presenting with isolated sixth cranial nerve palsy in a patient with systemic lupus erythematosus.

Cryptococcal meningitis is a rare complication of systemic lupus erythematosus (SLE). The nonspecific neurologic findings associated with this infection delays accurate diagnosis because initial neuropsychiatric manifestations of SLE are in instances indistinguishable from that of crytococcal meningitis. We report a case of cryptococcal meningitis presenting with unilateral sixth cranial nerve palsy in a male patient with SLE, which was successfully treated with antifungal agents.

Oral administration of type-II collagen suppresses IL-17-associated RANKL expression of CD4+ T cells in collagen-induced arthritis.

The receptor activator of nuclear factor kappaB ligand (RANKL) is an osteoclastogenic mediator, which is mainly expressed by stromal cells and osteoblast. However, T cells can also be an important provider for RANKL in special condition such as autoimmune arthritis. We examined the RANKL expression of hyporesponsive CD4+ T cells induced by oral feeding with type II collagen in collagen-induced arthritis (CIA) mice. The potential of RANKL expression in CD4+ T cells was downregulated in tolerance, as compared with CIA. One of possible explanations for this phenomenon is that CII-specific T cell activation was intrinsically impaired in oral tolerance, which caused suppression of RANKL expression of CD4+ T cells. We also investigated the extrinsic role of cytokine in this process. IL-17, well-known pro-inflammatory cytokine was upregulated in CIA and downregulated in tolerance. IL-17 had a potential to stimulate T cells to express RANKL in dose-dependent manner. IL-17-associated RANKL expression of CD4+ T cells was downregulated in oral tolerance, suggesting that the induction of tolerance ameliorates IL-17-induced RANKL expression of T cells in murine CIA. We also discovered that CIA - T cells could enhance osteoclastogenesis but not oral tolerance - T cells. Oral tolerance might be promising therapeutic option in viewpoints of modulating autoreactivity of CII which can induce not only IL-17 production but also RANKL expression in CD4+ T cells.

Pneumatosis cystoides intestinalis in relapsing polychondritis.

Relapsing polychondritis (RP) is a rare systemic disease characterized by an inflammatory process involving predominantly cartilaginous structures. Pneumatosis cystoides intestinalis (PCI) in RP has not been reported previously. We report a case of PCI in RP that was successfully treated with high oxygen and antibiotics.

Successful treatment of life-threatening intestinal ulcer in Behçet's disease with infliximab: rapid healing of Behçet's ulcer with infliximab.

Behçet's disease is a chronic, relapsing, multisystem inflammatory disorder characterized predominantly by recurrent orogenital ulcers, skin involvement, and uveitis. Recurrent mucocutaneous lesions may be the only symptom in mild cases, but ocular, gastrointestinal, and central nervous system involvement may occur in severe cases. We report in this study the successful treatment with infliximab of severe life-threatening GI bleeding caused by an ileal ulcer in a patient with Behçet's disease. Antitumor necrosis factor (TNF) therapy could be an emergency therapeutic option in patients with massively bleeding Behçet's disease and unstable patients or those with acute bleeding with other TNF-alpha-mediated autoimmune diseases. Another option for anti-TNF therapy could be as bridging management between conservative and surgical treatment.