Differential Regulation of RGS-2 by Constant and Oscillating PTH Concentrations

PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system. PTH was administered intermittently (4 min/h, 10⁻⁷ M) or continuously at an equivalent cumulative dose (6.6 × 10⁻⁹ M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor. In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13 and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling.     

Cutaneous miliary resistant tuberculosis in a patient infected with human immunodeficiency virus: case report and literature review

We report the case of a patient infected with human immunodeficiency virus who presented with fever and a disseminated papulous eruption, diagnosed as cutaneous miliary tuberculosis. The diagnosis was made by histological examination of a skin biopsy, which showed numerous acid‐fast bacilli. A culture grown from a skin biopsy isolated a resistant Mycobacterium tuberculosis strain. The papules disappeared within a few days after starting treatment with pyrazinamide, isoniazid and moxifloxacin.     

Onychomycosis caused by Fusarium solani in a woman with diabetes

A case of untreated fusarial onychomycosis leading to serious consequences is reported. Fusarium solani is a widespread fungus and an occasional human pathogen. It usually invades rapidly in immunocompromised hosts, and often results in a poor outcome despite treatment. We report a woman with diabetes mellitus who had untreated fusarial infection of the nails, which developed into subcutaneous fusariosis, superinfected by bacteria, and then evolved into osteomyelitis that subsequently resulted in septic shock. Early management of mycotic nails in immunocompromised hosts is crucial to prevent life‐threatening disease.     

Vascular endothelial growth factor in psoriasis: an indicator of disease severity and control

Background  Psoriasis is a chronic disease characterized by abnormal epidermal proliferation, inflammation and angiogenesis. It has been reported that vascular endothelial growth factor (VEGF) is overexpressed in lesional psoriatic skin and its serum levels are significantly elevated in patients with moderate to severe disease.
Objective  This study aims to evaluate the possible role of VEGF in the pathogenesis of psoriasis, and its significance as an indicator of disease severity and control.
Methods  Thirty patients with moderate to severe psoriasis and 10 healthy controls were subjected to baseline evaluation of VEGF. Patients were divided into three groups according to the received treatment: psoralen plus ultraviolet A (PUVA) thrice weekly (group 1), acitretin 50 mg daily (group 2), and combined PUVA twice weekly and acitretin 25 mg daily (group 3).Treatment continued for 16 weeks or up to clinical cure. Every patient was subjected to severity evaluation by Psoriasis Area and Severity Index (PASI) and measurement of serum VEGF before and after treatment.
Results  Mean serum levels of VEGF were significantly elevated in patients (327 ± 66.2 pg/mL) than control subjects (178 ± 83.4 pg/mL). A highly significant correlation was found between VEGF and PASI score, but not with other variables. The best clinical response, the least side-effects and the highest reduction of VEGF serum levels were achieved by the combined therapy.
Conclusion  The present study supported the proposed role of VEGF in the pathogenesis of psoriasis, and suggested that it could serve as a good indicator of disease severity and control.     

Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application

Background/aim  Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods  Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N₂ cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results  Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions  'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.