Scanning the immunopathogenesis of psoriasis

Psoriasis is a chronic inflammatory skin disease, the immunologic model of which has been profoundly revised following recent advances in the understanding of its pathophysiology. In the current model, a crosstalk between keratinocytes, neutrophils, mast cells, T cells, and dendritic cells is thought to create inflammatory and pro-proliferative circuits mediated by chemokines and cytokines. Various triggers, including recently identified autoantigens, Toll-like receptor agonists, chemerin, and thymic stromal lymphopoietin may activate the pathogenic cascade resulting in enhanced production of pro-inflammatory and proliferation-inducing mediators such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-23, IL-22, interferon (IFN)-α, and IFN-γ by immune cells. Among these key cytokines lie therapeutic targets for currently approved antipsoriatic therapies. This review aims to provide a comprehensive overview on the immune-mediated mechanisms characterizing the current pathogenic model of psoriasis

Cancer rate of the indeterminate lesions at low or high risk according to italian system for reporting of thyroid FNA

Background: Italian consensus for the classification and reporting of thyroid cytology (ICCRTC) has been used in almost all Italian institutions since 2014. High reliability of ICCRTC in classifying low and high risk indeterminate nodules (Tir 3A and Tir 3B, respectively) was demonstrated. Here we reviewed our casuistry of thyroid indeterminate lesions to analyze the histologic outcome. Methods: All lesions undergone FNA and final histology at S. Andrea Hospital of Rome after a cytologic assessment of Tir 3A and Tir 3B, according to ICCRTC, were included in the study. Results: A number of 157 indeterminate FNA was found after the introduction of ICCRTC. Of these, 75 undergone surgery and were finally included for the study. At histology we found a 33.3% of cancers and a 67.7% of benign lesions. Out of the overall series, 25 were classified as Tir 3A and 50 as Tir 3B. Cancer rate observed in Tir 3A (1/25, 4%) was significantly (p = 0.0002) lower than that of Tir 3B (24/50, 48%). No significant difference was found in age and size between the two subcategories. Conclusions: We confirm in our series that Italian consensus for the classification and reporting of thyroid cytology allows to discriminate indeterminate lesions at low and high risk of malignancy

Pattern of antibiotic consumption in two Italian production chains differing by the endemic status for Porcine Reproductive and Respiratory Syndrome

The aim of this case study was to quantify antibiotic (AB) use in Italian weaning (W) and fattening (F) units differentiated for porcine reproductive and respiratory syndrome (PRRS) occurrence. Farms were classified as either PRRS negative (–) or PRRS positive (+) based on the circulation of the virus among the animals. In all the farms, the modified live PRRS virus (PRRSV) vaccine was provided to all the animals. In the PRRS– farms, the level of circulating antibodies was low, and the disease, in its clinical form, did not occur. In the PRRS+ farms, the level of circulating antibodies against the virus was high, and the disease was recurrent. Data regarding AB consumption were collected from 2017 to 2020, and the active compounds (ACs) were expressed as milligrams of AC/total kilogram of body weight (BW) produced. Each AC was classified into one of four categories according to the EuropeanMedicines Agency classification of ABs for prudent and responsible use in animals: Avoid, Restrict, Caution, and Prudence. Data regarding the ACs in each category were analyzed using a linear model that included production phase, PRRS status, and their interaction as factors. Performance parameters, average age of the pigs at the end of each phase, daily live weight gain, feed-to-gain ratio, total losses, cost index, and medication costs were significantly influenced by the PRRS chain. The use of class B ABs was not affected by production phase or PRRS status. Conversely, for class C ABs, interaction between the two factors (p = 0.02) was observed; W/PRRS+ and F/PRRS+ showed the greatest AB use for this class (p = 0.003). For class D ABs, the interaction was significant (p = 0.01); class C and D ABs were used more in the weaning (p = 0.07) than in the fattening phase (p = 0.003). For the weaning phase, the use of class C and D ABs was greater in the PRRS+ than in the PRRS– chain (p < 0.01). In conclusion, PRRS status affected the growth of pigs and economic performance. Moreover, PRRS status significantly influenced the use of ABs during all the growing periods with the greatest impact being on the weaning phase

Adenopathy and extensive skin patch overlying a plasmacytoma (AESOP) syndrome

Adenopathy and extensive skin patch overlying a plasmacytoma is a very rare syndrome featuring a red-to-brown, violaceous skin patch along with a plasmacytoma. Only 11 case reports exist in the literature. Skin biopsies from the cutaneous patch overlying the plasmacytoma exhibit a dermal vascular hyperplasia with increased surrounding dermal mucin. Radiation therapy is used to treat and cure the plasmacytoma

The Src and signal transducers and activators of transcription pathways as specific targets for low molecular weight phosphotyrosine-protein phosphatase in platelet-derived growth factor signaling.

Abstract The low molecular weight phosphotyrosine-protein phosphatase (LMW-PTP) is a cytosolic phosphotyrosine-protein phosphatase specifically interacting with the activated platelet-derived growth factor (PDGF) receptor through its active site. Overexpression of the LMW-PTP results in modulation of PDGF-dependent mitogenesis. In this study we investigated the effects of this tyrosine phosphatase on the signaling pathways relevant for PDGF-dependent DNA synthesis. NIH 3T3 cells were stably transfected with active or dominant negative LMW-PTP. The effects of LMW-PTP were essentially restricted to the G1 phase of the cell cycle. Upon stimulation with PDGF, cells transfected with the dominant negative LMW-PTP showed an increased activation of Src, whereas the active LMW-PTP induced a reduced activation of this proto-oncogene. We observe that c-Src binding to PDGF receptor upon stimulation is prevented by overexpression of LMW-PTP. These effects were associated with parallel changes in myc expression. Moreover, wild-type and dominant negative LMW-PTP differentially regulated STAT1 and STAT3 activation and tyrosine phosphorylation, whereas they did not modify extracellular signal-regulated kinase activity. However, these modifications were associated with changes in fos expression despite the lack of any effect on extracellular signal-regulated kinase activation. Other independent pathways involved in PDGF-induced mitogenesis, such as phosphatidylinositol 3-kinase and phospholipase C-γ1, were not affected by LMW-PTP. These data indicate that this phosphatase selectively interferes with the Src and the STATs pathways in PDGF downstream signaling. The resulting changes in myc andfos proto-oncogene expression are likely to mediate the modifications observed in the G1 phase of the cell cycle

Recombinant activated protein C treatment improves tissue perfusion and oxygenation in septic patients measured by near-infrared spectroscopy

INTRODUCTION: The purpose was to test the hypothesis that muscle perfusion, oxygenation, and microvascular reactivity would improve in patients with severe sepsis or septic shock during treatment with recombinant activated protein C (rh-aPC) (n = 11) and to explore whether these parameters are related to macrohemodynamic indices, metabolic status or Sequential Organ Failure Assessment (SOFA) score. Patients with contraindications to rh-aPC were used as a control group (n = 5). MATERIALS AND METHODS: Patients were sedated, intubated, mechanically ventilated, and hemodynamically monitored with the PiCCO system. Tissue oxygen saturation (StO2) was measured using near-infrared spectroscopy (NIRS) during the vascular occlusion test (VOT). Baseline StO2 (StO2 baseline), rate of decrease in StO2 during VOT (StO2 downslope), and rate of increase in StO2 during the reperfusion phase were (StO2 upslope) determined. Data were collected before (T0), during (24 hours (T1a), 48 hours (T1b), 72 hours (T1c) and 96 hours (T1d)) and 6 hours after stopping rh-aPC treatment (T2) and at the same times in the controls. At every assessment, hemodynamic and metabolic parameters were registered and the SOFA score calculated. RESULTS: The mean +/- standard deviation Acute Physiology and Chronic Health Evaluation II score was 26.3 +/- 6.6 and 28.6 +/- 5.3 in rh-aPC and control groups, respectively. There were no significant differences in macrohemodynamic parameters between the groups at all the time points. In the rh-aPC group, base excess was corrected (P < 0.01) from T1a until T2, and blood lactate was significantly decreased at T1d and T2 (2.8 +/- 1.3 vs. 1.9 +/- 0.7 mmol/l; P < 0.05). In the control group, base excess was significantly corrected at T1a, T1b, T1c, and T2 (P < 0.05). The SOFA score was significantly lower in the rh-aPC group compared with the controls at T2 (7.9 +/- 2.2 vs. 12.2 +/- 3.2; P < 0.05). There were no differences between groups in StO2 baseline. StO2 downslope in the rh-aPC group decreased significantly at all the time points, and at T1b and T2 (-16.5 +/- 11.8 vs. -8.1 +/- 2.4%/minute) was significantly steeper than in the control group. StO2 upslope increased and was higher than in the control group at T1c, T1d and T2 (101.1 +/- 62.1 vs. 54.5 +/- 23.8%/minute) (P < 0.05). CONCLUSIONS: Treatment with rh-aPC may improve muscle oxygenation (StO2 baseline) and reperfusion (StO2 upslope) and, furthermore, rh-aPC treatment may increase tissue metabolism (StO2 downslope). NIRS is a simple, real-time, non-invasive technique that could be used to monitor the effects of rh-aPC therapy at microcirculatory level in septic patient

Dynamic markers based on blood perfusion fluctuations for selecting skin melanocytic lesions for biopsy

Skin malignant melanoma is a highly angiogenic cancer, necessitating early diagnosis for positive prognosis. The current diagnostic standard of biopsy and histological examination inevitably leads to many unnecessary invasive excisions. Here, we propose a non-invasive method of identification of melanoma based on blood flow dynamics. We consider a wide frequency range from 0.005 – 2 Hz associated with both local vascular regulation and effects of cardiac pulsation. Combining uniquely the power of oscillations associated with individual physiological processes we obtain a marker which distinguishes between melanoma and atypical nevi with sensitivity of 100% and specificity of 90.9%. The method reveals valuable functional information about the melanoma microenvironment. It also provides the means for simple, accurate, in vivo distinction between malignant melanoma and atypical nevi, and may lead to a substantial reduction in the number of biopsies currently undertaken