Annular Lichenoid Dermatitis (of Youth)

About 20 years after its first description, Annular Lichenoid Dermatitis of Youth (ALDY) is recognized as a distinctive lichenoid dermatosis with specific clinical and histological features. The disease occurs mostly in young persons all over the world, runs a chronic course, and has an obscure etiopathogenesis. Clinically, lesions consist of persistent, asymptomatic erythematous macules and round-oval annular patches with a red-violaceous non-scaling border and central hypopigmentation, mostly localized on the groin and flanks. Histology shows a peculiar lichenoid dermatitis characterized by irregular epidermal hyperplasia with an alternation of thinned and quadrangular rete ridges and a dense band-like lichenoid infiltrate of lymphocytes in the papillary dermis. Typically, there is infiltration of lymphocytes into the lower epidermal layers with massive necrosis/apoptosis of keratinocytes, which is limited to the tips of rete ridges. Dermal lymphocytes are usually CD3+, CD4+, while most of the intraepidermal T cells are CD8+. Analysis of TCR-γ-chain gene rearrangement displayed polyclonality in all cases examined. Differential diagnosis mainly includes morphea, mycosis fungoides, annular erythemas and inflammatory lesions of vitiligo. Topical corticosteroids and topical tacrolimus represent the most effective drugs for ALDY treatment.

68Ga-FAPI-04 PET Distinguishes Malignancy from Inflammatory Lesions

Background The 68Ga-labelled FAPI provides new oncology imaging option other than 18F-FDG-PET. However, it's unclear about whether the FAPI-PET distinguishes malignancy from benign lesions. Methods We established an AOM/DSS-induced rat colorectal tumor model. A double PET/CT tracer of 68Ga-FAPI-04 and 18F-FDG was used in the rat colorectal tumor model. Histological examination, immunohistochemistry staining, and radioautography were performed in this study. Results 68Ga-FAPI PET imaging distinguishes neoplasia from inflammatory lesions in an AOM/DSS-induced rat colorectal tumor model, and FAPI accumulation gradually increases along with tumor progression. An inflammatory lesion did not interfere with 68Ga-FAPI PET imaging. Conclusion The 68Ga-FAPI-04 PET distinguishes malignant tumors from inflammatory lesions by detecting FAP in a rat colorectal tumor model, suggesting that 68Ga-FAPI-04 PET is a better diagnostic tool than 18F-FDG PET, at least to colorectal cancer patients.

Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis

Background Hydroxychloroquine (HCQ) has been recommended as a basic treatment for lupus nephritis (LN) during this decade based on its ability to improve LN-related renal immune-mediated inflammatory lesions. As a classical lysosomal inhibitor, HCQ may inhibit lysosomal degradation and disrupt protective autophagy in proximal tubular epithelial cells (PTECs). Therefore, the final renal effects of HCQ on LN need to be clarified. Method HCQ was administered on spontaneous female MRL/lpr LN mice with severe proteinuria daily for 4 weeks. Moreover, the MRL/lpr mice with proteinuric LN were subjected to cisplatin-induced or unilateral ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) after 2 weeks of HCQ preadministration. Results As expected, HCQ treatment increased the survival ratio and downregulated the levels of serum creatinine in the mice with LN, ameliorated renal lesions, and inhibited renal interstitial inflammation. Unexpectedly, HCQ preadministration significantly increased susceptibility to and delayed the recovery of AKI complicated by LN, as demonstrated by an increase in PTEC apoptosis and expression of the tubular injury marker KIM-1 as well as the retardation of PTEC replenishment. HCQ preadministration suppressed the proliferation of PTECs by arresting cells in G1/S phase and upregulated the expression of cell cycle inhibitors. Furthermore, HCQ preadministration disrupted the PTEC autophagy-lysosomal pathway and accelerated PTEC senescence. Conclusion HCQ treatment may increase susceptibility and delay the recovery of AKI complicated by LN despite its ability to improve LN-related renal immune-mediated inflammatory lesions. The probable mechanism involves accelerated apoptosis and inhibited proliferation of PTECs via autophagy-lysosomal pathway disruption and senescence promotion.

Efficacy of a Retinoid, Keratolytic, Anti-Inflammatory and Antibacterial Gel and Spray Formulations in Mild Common Acne

Background and Objectives: For the treatment of mild/moderate acne, topical retinoids and antibacterial molecules are used in monotherapy or in combination. An exfoliating and anti-inflammatory action can increase the clinical efficacy of this therapeutic approach. A topical product in Gel and Spray Formulations (GF and SF) with retinoids (hydroxypinacolone retinoate and encapsulated retinol), with anti-inflammatory (niacinamide), antibacterial (biopep15) and keratolytic (glycolic and salicylic acids) activity has recently been developed. Topical retinoids have anti-inflammatory, anti-seborrheic and anticomedone-formation properties. Biopep15 is an oligopeptide with antibacterial action that can interfere with lipoteichoic acid, a component of the wall of Cutibacterium acnes. In addition, Biopep15 can perform also an antagonistic action against the Toll-Like-Receptor 2, involved in the pathogenesis of acne. Niacinamide has a well-known anti-inflammatory action. Salicylic and glycolic explain keratolytic and exfoliating activities. In this study the objective was to determine the efficacy and tolerability of GF and SF in mild/ moderate comedogenic acne. Methods: In a 4-week, open-label, prospective trial, 32 patients between the ages of 15 and 30 have been evaluated. All participants gave their written consent. Treatment with gel (for facial lesions) and spray (for lesions located on thorax, back and shoulder) applied twice daily were used. To assess clinical efficacy, a count of comedogenic lesions (open and closed comedones; non-inflammatory lesions: NIL) and inflammatory lesions (IL; papules, and pustules) was performed and the reduction in the number of lesions after 2 and 4 weeks of treatment was evaluated. An evaluation of Total lesions count (TL; NIL+IL) was also performed.The lesion count data were analysed with a paired Student's t test.We evaluated also the exfoliating/keratolytic activity and the effect on sebum production assessed at baseline, after 2 and 4 weeks of treatment. Finally, to evaluate Cutibacterium acnes (C. acnes) skin colonization, we performed a fluorescence detection of skin porphyrin content at baseline and at day 28, by mean of Visiopor PP 34 camera. Results: All patients completed the trial. At baseline the NIL, IL and TL count were 14.3, 8.7 and23, respectively. After 2 weeks of GF/SF treatment, NIL, IL and TL significantly decreased to 9.7 (-32%), 6.8 (-22%) and 16.5 (-29%), respectively. At the end of the treatment, a significant reduction in comparison with baseline was observed for NIL (-49%) IL (-63%) and TL (-54%). The exfoliating index evaluated in comparison with baseline value improved not significantly by 13% at day 14, and significantly (p=0.05) by 18% at day 24. The Cutibacterium acnes skin colonization area was significantly (p=0.02) reduced by 28% in comparison with baseline. Treatment was well tolerated, and local tolerability was assessed as optimal by all patients. Conclusion: This new anti-acne combination formula based on retinoids, antibacterial oligopeptide, keratolytic and anti-inflammatory agents have shown high clinical efficacy and good tolerability in patients with mild to moderate acne. The treatment shows also a keratolytic effect and a significant reduction of C. acnes skin colonization.

Diffusion tensor imaging in unclear intramedullary tumor-suspected lesions allows separating tumors from inflammation

Design Prospective diagnostic study. Objectives Primary imaging-based diagnosis of spinal cord tumor-suspected lesions is often challenging. The identification of the definite entity is crucial for dedicated treatment and therefore reduction of morbidity. The aim of this trial was to investigate specific quantitative signal patterns to differentiate unclear intramedullary tumor-suspected lesions based on diffusion tensor imaging (DTI). Setting Medical Center - University of Freiburg, Germany. Methods Forty patients with an unclear tumor-suspected lesion of the spinal cord prospectively underwent DTI. Primary diagnosis was determined by histological or clinical work-up or remained indeterminate with follow-up. DTI metrics (FA/ADC) were evaluated at the central lesion area, lesion margin, edema, and normal spinal cord and compared between different diagnostic groups (ependymomas, other spinal cord tumors, inflammations). Results Mean DTI metrics for all spinal cord tumors (n = 18) showed significantly reduced FA and increased ADC values compared to inflammatory lesions (n = 8) at the lesion margin (p < 0.001, p = 0.001) and reduced FA at the central lesion area (p < 0.001). There were no significant differences comparing the neoplastic subgroups of ependymomas (n = 10) and other spinal cord tumors (n = 8), but remaining differences for both compared to the inflammation subgroup. We found significant higher ADC (p = 0.040) and a trend to decreased FA (p = 0.081) for ependymomas compared to inflammations at the edema. Conclusion Even if distinct differentiation of ependymomas from other spinal cord neoplasms was not possible based on quantitative DTI metrics, FA and ADC were feasible to separate inflammatory lesions. This may avoid unnecessary surgery in patients with unclear intramedullary tumor-suspected lesions.

Evaluation of [68Ga]Ga-NODAGA-RGD for PET Imaging of Rat Autoimmune Myocarditis

The 68Gallium-labeled 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid conjugated radiolabelled arginine-glycine-aspartic acid peptide ([68Ga]Ga-NODAGA-RGD) is a positron emission tomography (PET) tracer binding to cell surface receptor αvβ3 integrin that is upregulated during angiogenesis and inflammation. We studied whether αvβ3 targeting PET imaging can detect myocardial inflammation in a rat model of autoimmune myocarditis. To induce myocarditis, rats (n = 8) were immunized with porcine cardiac myosin in complete Freund's adjuvant on days 0 and 7. Control rats (n = 8) received Freund's adjuvant alone. On day 21, in vivo PET/CT imaging with [68Ga]Ga-NODAGA-RGD followed by ex vivo autoradiography and immunohistochemistry were carried out. Inflammatory lesions were detected histologically in the myocardium of 7 out of 8 immunized rats. In vivo PET images showed higher [68Ga]Ga-NODAGA-RGD accumulation in the myocardium of rats with inflammation than the non-inflamed myocardium of control rats (SUVmean 0.4 ± 0.1 vs. 0.1 ± 0.02; P = 0.00006). Ex vivo autoradiography and histology confirmed that [68Ga]Ga-NODAGA-RGD uptake co-localized with inflammatory lesions containing αvβ3 integrin-positive capillary-like structures. A non-specific [68Ga]Ga-DOTA-(RGE)2 tracer showed 76% lower uptake than [68Ga]Ga-NODAGA-RGD in the inflamed myocardium. Our results indicate that αvβ3 integrin-targeting [68Ga]Ga-NODAGA-RGD is a potential PET tracer for the specific detection of active inflammatory lesions in autoimmune myocarditis.

Selenium and Taurine Combination Is Better Than Alone in Protecting Lipopolysaccharide-Induced Mammary Inflammatory Lesions via Activating PI3K/Akt/mTOR Signaling Pathway by Scavenging Intracellular ROS

Mastitis is mainly induced by gram-negative bacterial infections, causing devastating economic losses to the global cattle industry. Both selenium (Se) and taurine (Tau) exhibit multiple biological effects, including reducing inflammation. However, no studies have reported the protective effect of the combined use of Se and Tau against mastitis, and the underlying mechanisms remain unclear. In this study, lipopolysaccharide (LPS), the vital virulence factor of gram-negative bacteria, was used to construct the in vivo and vitro mastitis models. The results of in vivo model showed that Se and Tau combination was more effective than either substance alone in reducing tissue hyperemia, edema, and neutrophil infiltration in the mammary acinar cavity, improving the blood-milk barrier in LPS-induced mice mastitis, and decreasing the expression of proinflammatory factors and the activity of MPO. Moreover, Se and Tau combination significantly increased the levels of LPS-induced reduction in PI3K/Akt/mTOR, but the expressions of TLRs and NLRP3 were not significantly changed in the mammary tissue. In the in vitro experiments, the effects of Se and Tau combination or alone on inflammatory factors, inflammatory mediators, MPO activity, and blood-milk barrier were consistent with those in vivo. The Se and Tau combination has also been found to increase the survival rate of BMECs compared with each substance alone via promoting cellular proliferation and inhibiting apoptosis. Also, it has been confirmed that this combination could restore the LPS-induced inhibition in the PI3K/Akt/mTOR signaling pathway. Inhibition of mTOR by Rapamycin counteracted the combined protection of SeMet and Tau against LPS-induced inflammatory damage, the inhibition of PI3K by LY294002 blocked the activation of mTOR, and the accumulation of ROS by the ROS agonist blocked the activation of PI3K. In conclusion, these findings suggested that Se and Tau combination was better than either substance alone in protecting LPS-induced mammary inflammatory lesions by upregulating the PI3K/Akt/mTOR signaling pathway.

Sensitivity of Propionibacterium acnes towards Commercial Anti-Acne Formulations

Propionibacterium acnes are aerotolerant anaerobic, gram-positive bacilli that form part of normal flora. They produce several pro-inflammatory substances that can trigger an immune response in the host by an influx of inflammatory leukocytes into the strands, causing inflammatory lesions that leave behind scars. Repeated isolation of Propionibacterium acnes may reduce efficacy among the resistant types, clearly explaining Acne lesions' importance. The Counter acne therapies are often the first treatment choice due to the convenience of cost and time over clinical appointments. However, not all of the commercially available anti-acne formulations are supported by clinical studies. The present study was conducted to test the efficacy of selected commercial anti-acne gel formulations. The microscopic observation and biochemical studies conform to the presence of anti-acne activity. A sensitivity test was performed on all the isolates of Propionibacterium acnes by well diffusion technique. The selected over-the-counter anti-acne gel formulations failed to produce any inhibition zone.

Dynamic Doppler Ultrasound Assessment of Tissue Perfusion Is a Better Tool than a Single Vessel Doppler Examination in Differentiating Malignant and Inflammatory Pancreatic Lesions

Dynamic tissue perfusion measurement (DTPM) and single vessel flow measurement (SVFM) were assessed in differentiating inflammatory and malignant lesions of the pancreas. Sixty-nine patients (age 62.0 ± 14.7; 33 Female and 36 Men; 40 with malignant and 29 with inflammatory lesions) in whom during the endoscopic ultrasound (EUS) of focal pancreatic lesions it was possible to adequately evaluate the flow in the color Doppler, and then perform a biopsy, were qualified for the study. The assessed DTPM parameters flow velocity (TFV), perfusion intensity (TPI), and resistive index (TRI) as well as the following SVFM parameters: flow velocity (FV), volume flow (VolF), and resistive index (RI) differed significantly between the malignant and inflammatory lesions (p < 0.005). TFV and TPI have slightly better discriminatory properties than the corresponding FV and VolF parameters (p < 0.10). Considering the Doppler parameters usually evaluated in a given method, the TPI = 0.009 cm/s (sensitivity 79%, specificity 92%, AUC 0.899, p < 0.001) was significantly better (p = 0.014) in differentiating between inflammatory and malignant pancreatic lesions in comparison to FV = 2.526 cm/s (sensitivity 79%, specificity 70%, AUC 0.731, p < 0.001). Tissue perfusion has better discriminatory properties in the differentiation of solid pancreatic lesions than the Doppler blood flow examination in the single vessel within the tumor.

Determination of capability of biofilm formation of strains s.aureus selected from the upper respiratory tract

Millions of people have died from acute infections in the past century, but they have been effectively fought through the development of modern vaccines, antibiotics and infection control measures. Chronic infections are slower than acute infections, and the symptoms are often vague, difficult, and sometimes impossible to cure with antibiotics. Important signs of chronic biofilm infections are extreme resistance to antibiotics and many other common antimicrobials, as well as the extraordinary ability to avoid the host’s defenses. One such disease is chronic inflammatory lesions of the tonsils, the main infectious agents of which are gram-positive cocci, strains Staphylococcus spp., Streptococcus spp. The purpose of the study of the ability of strains of Staphylococcus aureus to form a biofilm isolated from the surface of the epithelium of the upper respiratory tract of children. Clinical strains of Staphylococcus aureus bacteria obtained from the oropharynx of 32 children with tonsils affected by the inflammatory process at the age of 4-12 years (median – 7) were studied. The results of microbiological examination of biomaterial obtained from children with chronic inflammatory lesions of the tonsils showed that in 32 samples 25 strains of S. aureus were identified, 12 of them (48%) are capable of forming a biofilm, and 13 strains (52%) (not adhesive) are not had this ability. The study of the dynamics of biofilm formation by selected strains of S. aureus showed an increase in optical density (OS) during three days of cultivation, ranging from 0.143