Psoriasis is a chronic inflammatory immune-mediated disorder associated and often coexisting with many other immune-related clinical conditions including those affecting the gastrointestinal tract. Data obtained from the reviewed literature suggest an association between psoriasis and pathologies of the oral cavity, both psoriasis-specific lesions, as well as non-specific, such as geographic tongue or fissured tongue. These findings show the importance of thorough examination of oral mucosa in psoriatic patients. Inflammatory bowel diseases (IBD) are also linked with psoriasis. Crohn’s disease and ulcerative colitis share a common genetic background, inflammatory pathways and have an evident iatrogenic anti-TNF treatment link, necessitating dermatological or gastroenterological care in patients with IBD or psoriasis, respectively, as well as treatment adjusted to manifestations. The presence of celiac disease-specific antibodies in psoriatic patients and their correlation with the severity of the disease show the association between these disorders. The linking pathogenesis comprises vitamin D deficiency, immune pathway, genetic background and increase in the intestinal permeability, which suggests a potential benefit from gluten-free diet among psoriatic patients. The link between psoriasis and non-alcoholic fatty liver disease implies screening patients for components of metabolic syndrome and lifestyle changes necessity. Some studies indicate increased prevalence of cancer in patients with psoriasis, probably due to negative influence of skin lesion impact on lifestyle rather than the role of psoriasis in carcinogenesis. However, there are no sufficient data to exclude such an oncogenic hit, which is yet to be confirmed. Therefore, all psoriasis-associated comorbidities establish the importance of a multidisciplinary approach in the treatment of these patients.
Amphotericin B (AmB) is a very potent antifungal drug with very rare resistance among clinical isolates. Treatment with the AmB formulations available currently is associated with severe side effects. A promising strategy to minimize the toxicity of AmB is reducing its dose by combination therapy with other antifungals, showing synergistic interactions. Therefore, substances that display synergistic interactions with AmB are still being searched for. Screening tests carried out on several dozen of synthetic 1,3,4-thiadiazole derivatives allowed selection of a compound called 4-(5-methyl-1,3,4-thiadiazole-2-yl) benzene-1,3-diol (abbreviated as C1), which shows strong synergistic interaction with AmB and low toxicity towards human cells. The aim of the present study was to investigate the type of in vitro antifungal interactions of the C1 compound with AmB against fungal clinical isolates differing in susceptibility. The results presented in the present paper indicate that the C1 derivative shows strong synergistic interaction with AmB, which allows the use of a dozen to several dozen times lower AmB concentration necessary for 100% inhibition of the growth of pathogenic fungi in vitro. Synergistic interactions were noted for all tested strains, including strains with reduced sensitivity to AmB and azole-resistant isolates. These observations give hope for the possibility of application of the AmB - C1 combinatory therapy in the treatment of fungal infections.
Introduction: Patients with psoriasis and psoriatic arthritis (PsA) have metabolic disturbances, which may be due to chronic inflammation. Aim: Because interleukin-6 (IL-6) regulates both metabolic and inflammatory processes, we evaluated IL-6 as a potential marker of inflammation and metabolic disturbances in psoriasis. Material and methods: This study involved 93 patients with psoriasis, including 31 patients with concurrent PsA. We investigated whether serum markers of lipid metabolism and inflammation, including IL-6, were related to each other and to disease activity. Results: We found that concurrent PsA was associated with higher serum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and IL-6. In patients with psoriasis alone, the IL-6 serum concentration correlated positively with the concentrations of TC and LDL-c and with erythrocyte sedimentation rates (ESRs). Moreover, IL-6 concentrations tended to correlate positively with the percentage of the body area affected by psoriatic lesions. Among all patients, those with normal blood lipids had lower ESRs and IL-6 concentrations than patients with abnormal blood lipids. A logistic regression model showed that PsA, Psoriasis Area Severity Index (PASI), and ESR were significant predictors of the serum IL-6 concentration. Conclusions: Interleukin-6 may be an indicator of inflammatory activity in psoriasis. Moreover, IL-6 may be related to lipid abnormalities in patients with this disease.
Introduction: Statins may reduce the severity of psoriasis, but the available evidence is unclear. We conducted a meta-analysis of randomized controlled studies (RCTs) that investigated the effect of statins on psoriasis severity assessed with the Psoriasis Area and Severity Index (PASI). Material and methods: Two investigators searched independently the following databases: Medline, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to February 2019. Additionally, reference lists from all available articles were searched manually. We included only RCTs carried out among adult (≥ 16 years) patients with psoriasis who received oral statins for ≥ 8 weeks and had psoriasis severity assessed with the PASI at baseline and at the end of follow-up. We used random effects meta-analysis to calculate the mean difference (D) in PASI change between patients who received either a statin or a comparator. Results: Of 279 records identified, there were 5 eligible RCTs, with a total of 223 patients, including 128 patients who received a statin (atorvastatin or simvastatin). The improvement in psoriasis severity (PASI) was significantly greater in patients who received statins than in those who received comparators (D = 2.76, 95% CI: 0.49-5.04, p = 0.017). In subgroup analyses, the improvement in PASI values was significant for simvastatin (D = 3.70, 95% CI: 2.52-4.89, p < 0.001) but not for atorvastatin (D = 2.30, 95% CI:-1.28-5.88, p = 0.210). Conclusions: Oral statins may improve psoriasis, particularly in patients with severe disease. This observation should be verified in long-term, well-designed studies that will enable analyses adjusted for clinical variables.
Compounds belonging to the group of 5-substituted 4-(1,3,4-thiadiazol-2-yl) benzene-1,3-diols exhibit a broad spectrum of biological activity, including antibacterial, antifungal, and anticancer properties. The mechanism of the antifungal activity of compounds from this group has not been described to date. Among the large group of 5-substituted 4-(1,3,4-thiadiazol-2-yl) benzene-1,3-diol derivatives, the compound 4-(5-methyl-1,3,4-thiadiazole-2-yl) benzene-1,3-diol, abbreviated as C1, was revealed to be one of the most active agents against pathogenic fungi, simultaneously with the lowest toxicity to human cells. The C1 compound is a potent antifungal agent against different Candida species, including isolates resistant to azoles, and molds, with MIC100 values ranging from 8 to 96 μg/ml. The antifungal activity of the C1 compound involves disruption of the cell wall biogenesis, as evidenced by the inability of cells treated with C1 to maintain their characteristic cell shape, increase in size, form giant cells and flocculate. C1-treated cells were also unable to withstand internal turgor pressure causing protoplast material to leak out, exhibited reduced osmotic resistance and formed buds that were not covered with chitin. Disturbances in the chitin septum in the neck region of budding cells was observed, as well as an uneven distribution of chitin and β(1→3) glucan, and increased sensitivity to substances interacting with wall polymerization. The ATR-FTIR spectral shifts in cell walls extracted from C. albicans cells treated with the C1 compound suggested weakened interactions between the molecules of β(1→3) glucans and β(1→6) glucans, which may be the cause of impaired cell wall integrity. Significant spectral changes in the C1-treated cells were also observed in bands characteristic for chitin. The C1 compound did not affect the ergosterol content in Candida cells. Given the low cytotoxicity of the C1 compound to normal human dermal fibroblasts (NHDF), it is possible to use this compound as a therapeutic agent in the treatment of surface and gastrointestinal tract mycoses.
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