Search

Abstract Background Studies suggest that leucine supplementation (LS) has a therapeutic potential to prevent obesity and to promote glucose homeostasis. Furthermore, regular physical exercise is a widely accepted strategy for body weight maintenance and also for the prevention of obesity. The aim of this study was to determine the effect of chronic LS alone or combined with endurance training (ET) as potential approaches for reversing the insulin resistance and obesity induced by a high-fat diet (HFD) in rats. Methods Forty-seven rats were randomly divided into two groups. Animals were fed a control diet-low fat (n = 10) or HFD (n = 37). After 15 weeks on HFD, all rats received the control diet-low fat and were randomly divided according to treatment: reference (REF), LS, ET, and LS+ET (n = 7-8 rats per group). After 6 weeks of treatment, the animals were sacrificed and body composition, fat cell volume, and serum concentrations of total cholesterol, HDL-cholesterol, triacylglycerol, glucose, adiponectin, leptin and tumor necrosis factor-alpha (TNF-α) were analyzed. Results At the end of the sixth week of treatment, there was no significant difference in body weight between the REF, LS, ET and LS+ET groups. However, ET increased lean body mass in rats (P = 0.019). In addition, ET was more effective than LS in reducing adiposity (P = 0.019), serum insulin (P = 0.022) and TNF-α (P = 0.044). Conversely, LS increased serum adiponectin (P = 0.021) levels and reduced serum total cholesterol concentration (P = 0.042). Conclusions The results showed that LS had no beneficial effects on insulin sensitivity or adiposity in previously obese rats. On the other hand, LS was effective in increasing adiponectin levels and in reducing total cholesterol concentration.

Context.—: Clinical, dermoscopic, and histologic diagnostic criteria may overlap in cases with scarring and nonscarring alopecia, making diagnosis difficult for clinicians and pathologists. New histopathologic discoveries indicate that the cutaneous adnexal structural and homeostatic unit made up of the pilosebaceous unit, eccrine sweat gland coils (ESGCs), and dermal white adipose tissue may have a role in hair follicle renewal., Objective.—: To verify the presence of adipose tissue in the dermis at the level of the isthmus, infiltrating the bundles of the arrector pili muscle in biopsies from the scalp of 3 scarring alopecias: frontal fibrosing alopecia (FFA), fibrosing alopecia in a pattern distribution (FAPD), and lichen planopilaris (LPP)., Design.—: We performed a retrospective and descriptive survey of 71 female scalp biopsies from 2016 to 2022 diagnosed at the Dermatopathology Laboratory at Fluminense Federal University of Rio de Janeiro. Two pathologists reviewed and diagnosed the cases, correlating pathologic features with clinical and dermoscopic findings., Results.—: The histopathologic findings of adipose tissue infiltration in the dermis at the level of the isthmus and in the bundles of the arrector pili muscle and the displacement of ESGCs were more frequently identified in FFA, followed by FAPD and less frequently found in LPP., Conclusions.—: According to our research, adipose tissue infiltration in the dermis at the level of the isthmus and in the bundles of the arrector pili muscle and the displacement of ESGCs were observed in 3 scarring alopecias (FFA, FAPD, and LPP) and seems to be involved in the development of scarring alopecia., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Background: Merkel cell polyomavirus (MCPyV), a human polyomavirus that is unequivocally linked to merkel cell carcinoma (MCC), has been found in association with keratinocytes carcinomas (KC), especially basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Nevertheless, there is scarce information about the possible involvement of MCPyV in the development of KC., Objectives: To assess the presence of MCPyV DNA and Large-T Antigen (LT-Ag) via Polymerase Chain Reaction (PCR) and Immunohistochemistry (IHC) in cases of KC, and to correlate its presence with immunohistochemical markers p16, p53, and ki67, tumor type and subtype, sun-exposed location, and epidemiological data., Methods: The prevalence of MCPyV DNA, LT-Ag, and immunohistochemical markers p16, p53, and ki67 was assessed by PCR and Immunohistochemistry (IHC) in 127 cases of KC, these results were correlated with tumor type and subtype, sun-exposed location, and epidemiological data., Results: The MCPyV DNA was detected in 42.57% (43 of 101) cases by PCR, the LT-Ag was detected in 16.4% (20 of 122) of cases, p16 in 81.5% (97 of 119), p53 in 66.4% (83 of 125), ki67 in 89% (73 of 82). No correlation between MCPyV LT-Ag and DNA confronted with tumor type, subtype, location site, and immunohistochemical markers was found. A single correlation between the MCPyV LT-Ag and cSCC tumors and peri-tumoral lymphocyte cells was noted., Study Limitations: Further steps need to be taken to better evaluate the MCPyV influence and its possible role in KC carcinogenesis, as the evaluation of the virus genome state, the gene sequence that encodes LT-Ag in the KC tumor cells, and in situ hybridization for viral DNA or RNA in these cells., Conclusions: Despite the frequent detection of MCPyV in KC, the data available so far does not support the hypothesis of a causal relationship between them., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Viruses have been frequently identified in several human neoplasms, but the etiological role of these viruses in some tumors is still a matter of controversy. Polyomaviruses stand out among the main viruses with oncogenic capacity, specifically the Merkel cell polyomavirus (MCPyV). Recent revisions in the taxonomy of polyomaviruses have divided the Polyomaviridae family into six genera, including 117 species, with a total of 14 currently known human-infecting species. Although the oncogenicity of polyomaviruses has been widely reported in the literature since 1950, the first description of a polyomavirus as an etiological agent of a neoplasm in humans was made only in 2008 with the description of MCPyV, present in approximately 80% of cases of Merkel cell carcinoma (MCC), with the integration of its genome to that of the tumor cells and tumor-specific mutations, and it is considered the etiological agent of this neoplasm since then. MCPyV has also been detected in keratinocyte carcinomas, such as basal cell carcinoma and squamous cell carcinoma of the skin in individuals with and without immunosuppression. Data on the occurrence of oncogenic viruses potentially involved in oncogenesis, which cause persistence and tissue injury, related to the Merkel cell polyomavirus are still scarce, and the hypothesis that the Merkel cell polyomavirus may play a relevant role in the genesis of other cutaneous carcinomas in addition to MCC remains debatable. Therefore, the present study proposes to explore the current knowledge about the presence of MCPyV in keratinocyte carcinomas., (Copyright © 2023 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Daylight photodynamic therapy (DL-PDT) has similar efficacy to conventional photodynamic therapy in treating actinic keratosis (AKs). Good clinical outcomes have been reported when associated with physical methods such as microneedles, but a comparison of different methods and histologic studies is lacking., Objectives: To evaluate clinical and histologic modifications induced by standard DL-PDT and compare with DL-PDT associated with physical methods in treating skin field cancerization of the face., Methods: Forty patients with photodamaged skin and at least one AK lesion on the face were randomly distributed into four groups, ten patients in each (I: Standard DL-PDT; II: DL-PDT + microneedles; III: DL-PDT + CO2 laser; IV: DL-PDT + microdermabrasion) and underwent two DL-PDT sessions with methyl aminolevulinate cream and 2-hour daylight exposure. Skin biopsies were performed on all patients before and 3 months after. All fragments were stained using the hematoxylin-eosin, orcein, and picrosirius., Results: All 40 patients completed the study. Group III had a higher AK-clearance after 1 (p = 0,002) and 3 (p = 0,034) months, but it was similar in every group at 6 months (p = 0,441). Group III and IV had better clinical global improvement on texture, pigmentation and fine lines. In the groups associated with physical methods, the improvement of the keratinocytes' atypia and solar elastosis were remarkable. Only group III showed a significant reduction in solar elastosis (p = 0.034) and increased collagen type I (p = 0.028) after treatment., Conclusion: DL-PDT-associated with physical methods had better clinical and histologic results. AK-clearance were significantly higher after 1 and 3 months with pretreatment-CO2 laser. Photorejuvenation were more evident with pretreatment-CO2 laser and microdermabrasion. Pretreatment-CO2 laser showed a significant reduction in solar elastosis and increase of collagen type 1. These results pointed to the pretreatment with laser as a potentially better option for skin field cancerization of the face., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Sporotrichosis is the most common and least severe of deep mycoses. This disease has varied clinic presentation as well as several differential diagnosis., Methods: A cross-sectional and retrospective, individually based, observational study, based on records from the dermatopathology service of a university hospital in Brazil. A total of 175 patients were identified with clinical suspicion of sporotrichosis, from 2009 to 2017. Statistical analysis using prevalence ratios was conducted to characterize the clinicopathologic and epidemiological aspects., Results: The disease was suspected in 175 patients given the clinical presentation. Of these, 86 cases (49.14%) were sporotrichosis, 39 (22.29%) chronic granulomatous inflammatory processes of unidentified etiology, and 5 squamous cell carcinomas (2.86%). The majority of cases (52 or 60.46%) occurred in the upper limbs. A total of 40 samples presented a suppurative chronic granulomatous inflammatory process (46.51%). Only 5 samples (12.50%) showed positive staining (periodic-Schiff acid or GROCOTT)., Conclusions: The sporotrichosis cases underwent both cumulative and linear growth, especially in the group above 60 years. Squamous cell carcinomas appeared several times as a misdiagnosis of sporotrichosis by dermatologists, so it should be considered as an important differential diagnose due to the current context of skin cancers.

BACKGROUND Syringoid eccrine carcinoma (SEC) is an extremely rare malignant adnexal neoplasm derived from eccrine sweat glands, of unknown pathogenesis. We report a case of this rare entity presenting in the abdomen, which is the only one reported in this area and the only case of SEC in a patient with so many comorbidities. CASE REPORT A 58-year-old black male from Brazil reported a nodular lesion in the abdomen with a progressive increase in size and pain and local burning sensation. The histopathological examination showed a syringoid eccrine carcinoma. CONCLUSIONS We present a rare case of SEC and did an extensive literature review in order to describe the clinical characteristics, histopathological findings, immunohistochemical profile, treatments, and difficulties found in the diagnosis of this tumor. To avoid misdiagnosis, we gave special attention to biopsy quality.

Juvenile hyaline fibromatosis is a recessive autosomal hereditary disorder characterized by abnormal growth of hyalinized fibrous tissue. Its clinical presentation is marked by tumors of the skin, bone lesions, joint contractures, and gingival hyperplasia. We report a localized form of juvenile hyaline fibromatosis, a rare disease with several cases reported in the worldwide literature. A 23-year-old man presented with multiple tumors, joint contractures, and osteolytic bone lesions, but without gingival hyperplasia in one year of follow-up. Although, the onset of this condition is commonly in early childhood with progression, his unusual clinical presentation began at eight years of age with late progression in adolescence.

Background: Annexin A1 (ANXA1) and Translocator Protein-18KDa (TSPO) down-regulate neuroinflammation. We investigated the role of recombinant ANXA1 (rANXA) on TSPO functions on Toll Like Receptor (TLR) activated microglia., Methods: BV-2 cells (murine microglia), were stimulated by E. coli Lipopolysaccharide (LPS) and treated with rANXA1 in order to measure TSPO expression and inflammatory parameters. Anti-sense ANXA1 and TLR4 and TSPO shRNA, as well as pharmacological treatments, were employed to assess the mechanisms involved., Results: LPS-stimulated BV-2 cells caused overexpression of TSPO, which was inhibited by: pharmacological blockade of TLR4 or TLR4 mRNA silencing; inhibition of myeloid differentiation primary response gene 88 (MyD88) dimerization; or blocking of nuclear factor κB (NF-κB) activation. rANXA1 treatment impaired LPS-induced TSPO upregulation by down-modulating MyD88 and NF-κB signaling; the effect was abolished by WRW4, an antagonist of formyl peptide receptor 2 (FPR2). rANXA1 treatment also downregulated interleukin 1β (IL-1β) and tumor necrosis factor-α (TNFα) secretion in LPS-stimulated BV-2 cells. TSPO knockdown in BV-2 cells augmented LPS-induced TNFα secretion and abolished the inhibitory effect of rANXA1 on TNFα secretion evoked by LPS., Conclusions: exogenous ANXA1 down-modulates LPS-induced TSPO via MyD-88/NF-κB pathways, and constitutive TSPO is pivotal for the control of ANXA1 on TNFα secretion. TSPO actions may be involved with the mechanisms of ANXA1 on inflammatory brain diseases., (Copyright © 2018. Published by Elsevier Inc.)

The diagnosis of cutaneous melanoma in situ, considered to have excellent prognosis, has been increasingly frequent, with rare isolated reports of cutaneous melanoma in situ presenting recurrence, metastasis, and death. No specific study is found in the literature about these lesions of unexpected behavior. We describe the demographic and histopathological findings of 448 cases of cutaneous melanoma in situ in 369 patients, emphasizing the prognostic criteria of those with unfavorable outcomes, corresponding to 9 cases in which regression had no significant role. Adnexotropism was found in 44.5% of cases. The study of early lesions would allow clinicians to have a better understanding of the evolutionary processes of the disease.

In this study, it is shown a method for the determination of benzodiazepines and their main metabolites in urine samples by hollow-fiber liquid-phase microextraction (LPME) in the three-phase mode. Initially, the hydrolysis step was performed using 100 μL of sodium acetate 2.0 mol/L buffer solution (pH 4.5), 25 μL of β-glucuronidase enzyme and incubation for 90 min at 55 °C. In parallel with hydrolysis, the LPME fiber (9 cm) was prepared. Its pores were filled with a mixture of dihexyl ether: 1-nonanol (9:1). Afterwards, a solution of 3.0 mol/L of HCl was introduced into the lumen of the fiber (acceptor phase). After hydrolysis, the fiber was submersed in the alkalinized urine (pH 10) containing 10% NaCl. Samples were then submitted to orbital shaking (2400 rpm) for 90 min. The acceptor phase was later withdrawn from the fiber, dried and the residue derivatized with trifluoroacetic anhydride (TFAA) for 10 min at 60 °C with further addition of N-methyl-N-tert-butyldimethylsilyltrifluoroacetamide containing 1% tert-butyldimethylchlorosilane (MTBSTFA) for 45 min at 90 °C followed by determination by gas chromatography-mass spectrometry (GC-MS). The calibration curves obtained showed linearity over the specified range, with a similar sensitivity to traditional techniques and a higher detection capability compared to most of the miniaturized methods described in the literature. The method has been developed and successfully validated and applied to urine samples from real cases of benzodiazepines intake., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Cutaneous squamous cell carcinoma (SCC) is a malignant tumor that can occur in normal skin, but commonly evolves from precursor lesions. SCC arising in ulcers is a rare and often aggressive cutaneous malignancy that arises from chronic wounds or old scars and is the most common histological tumor type found in Marjolin ulcer. Most frequently occurs in patients of low socioeconomic status, with limited access to health services, as a result of burns and other neglected injuries. Herein, we report a case of squamous cell carcinoma originating from a longstanding decubitus ulcer in a 56-year-old paraplegic man.

Background: Striae distensae (SD) treatment still remains a therapeutic challenge to dermatologists. Ablative fractional laser and radiofrequency (RF) enhance skin-drug permeability for SD treatment., Objective: To clinically evaluate the efficacy and safety as well as patient's satisfaction in relation to a method using ablative fractional RF associated with retinoic acid 0.05% cream and an acoustic pressure wave ultrasound (US) in patients with alba-type SD on the breast., Methods and Materials: Eight patients with alba-type SD on the breast were treated with three step procedure: (1) fractional ablative RF for skin perforation; (2) topical application of retinoic acid 0.05% on the perforated skin; and (3) US was applied to enhance the retinoic acid penetration into the skin. Other eight patients with alba-type SD on the abdominal area were submitted to RF treatment isolated without retinoic acid or US. Three of them were submitted to skin biopsies., Results: Three patients with SD on the breast area improved from "severe" to "moderate;" two patients improved from "severe" to "mild;" two patients from "moderate" to "mild;" one patient from "marked" to "mild." Clinical assessment demonstrated significant improvement in the appearance of SD in all patients treated with RF associated with retinoic acid 0.05% cream and US (P = 0.008), with low incidence of side effects and high level of patient's satisfaction. Among the patients treated only with RF, two patients improved from "severe" to "marked;" one patient from "marked" to "moderate;" and one patient improved from "marked" to "mild." Four patients did not show any sort of improvement. Clinical assessment demonstrated no significant improvement in the appearance of SD treated with RF isolated with low incidence of side effects, but low-level of patient's satisfaction., Conclusion: Ablative fractional RF and acoustic pressure US associated with retinoic acid 0.05% cream is safe and effective for alba-type SD treatment., (Copyright © 2012 Wiley Periodicals, Inc.)

A fast method was optimized and validated in order to quantify amphetamine-type stimulants (amphetamine, AMP; methamphetamine, MAMP; fenproporex, FPX; 3,4-methylenedioxymethamphetamine, MDMA; and 3,4-methylenedioxyamphetamine, MDA) in human hair samples. The method was based in an initial procedure of decontamination of hair samples (50 mg) with dichloromethane, followed by alkaline hydrolysis and extraction of the amphetamines using hollow-fiber liquid-phase micro extraction (HF-LPME) in the three-phase mode. Gas chromatography-mass spectrometry (GC-MS) was used for identification and quantification of the analytes. The LoQs obtained for all amphetamines (around 0.05 ng/mg) were below the cut-off value (0.2 ng/mg) established by the Society of Hair Testing (SoHT). The method showed to be simple and precise. The intra-day and inter-day precisions were within 10.6% and 11.4%, respectively, with the use of only two deuterated internal standards (AMP-d5 and MDMA-d5). By using the weighted least squares linear regression (1/x²), the accuracy of the method was satisfied in the lower concentration levels (accuracy values better than 87%). Hair samples collected from six volunteers who reported regular use of amphetamines were submitted to the developed method. Drug detection was observed in all samples of the volunteers., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Unlabelled: Mycosis fungoides (MF), the most common form of cutaneous T cell lymphoma (CTCL), is mainly manifested in the elderly. However, it has been described in children and teenagers., Objectives: To report six patients with mycosis fungoides diagnosed in patients under 20 years of age. Our focus is on epidemiologic data, clinical features, histopathological aspects, and immunophenotypical findings., Methods: The files of all patients diagnosed with CTCL at Hospital Universitário Antônio Pedro (HUAP) / Universidade Federal Fluminense (UFF), Niterói, Brazil, from 2007 to 2010 were searched to identify patients under 20 years of age. Slides were reviewed with routine methods (H&E) and immunohistochemical stains by two dermatopathologists and one surgical pathologist., Results: Among a total of 66 patients with MF, six were children and adolescents between five and nineteen years of age. Most of them had dark skin and presented with the hypopigmented variant of MF; some expressed the T cell CD8+ phenotype, although the prognosis remains the same as for classical CTCL. The main histopathological findings were basilar lymphocytes, Pautrier microabscesses, eccrine infiltration, and dermal fibrosis. One patient had shown pityriasis lichenoides chronica for 10 years before the diagnosis of MF., Conclusions: The incidence of juvenile mycosis fungoides has increased, corresponding to 9.1 percent of patients diagnosed with MF in our institution in four years. In this sample, 83.3 percent of the patients had the hypopigmented variant and 50 percent of them showed the CD3+/CD8+ T cells phenotype. We emphasize the occurrence of pityriasis lichenoides chronica before the onset of MF in one of our cases. This association, although rare, must be considered in cases of atypical evolution of PLC. The diagnosis of hypopigmented MF should also be considered in patients when hypochromic patches are persistent. We would like to highlight the importance of Pautrier microabscesses, basilar distribution, and eccrine involvement by neoplastic lymphocytes as histopathological diagnostic criteria for this variant of MF.

Background: Sweet's syndrome refers to a set of cutaneous, systemic and histopathological alterations that occur in response to different stimuli, in a similar way to that occurring in erythema nodosum, erythema multiforme and leukocytoclastic vasculitis. The syndrome has been described in association with conditions such as infections, pregnancy, the use of certain medications and malignancy., Objectives: To evaluate the clinical and histopathological alterations occurring in this syndrome and to assess the association between these alterations and other conditions., Methods: A retrospective study of 73 cases was conducted, evaluating data on the microscopic examination of skin lesions, as well as clinical and laboratory data., Results: The majority of the patients were female (83.0%), white (49.2%) and between 30 and 60 years of age (73.8%). The principal alterations found were: erythymatous plaques (76.9%), papules (43.0%), pseudo-vesiculation (PV) (38.4%) and target lesions (18.5%). With respect to the associated conditions, upper respiratory tract infections (15.4%) and the use of medication (10.8%) were the most common. Other associations, albeit represented by only one case each, were: Hodgkin's lymphoma, pregnancy, ulcerative colitis, polycythemia vera and lupus erythematosus in a patient with acquired immune deficiency syndrome (AIDS). The principal microscopic findings were: neutrophils with leukocytoclasia (98.6%), collagen degeneration (87.7%), edema (74.0%) and PV (38.4%). The presence of eosinophils (41.1%) ranged from rare to abundant and was usually unrelated to the use of medication. Inflammatory infiltrate reached the deep epidermal layer in 47.9% of cases and panniculitis was found in 80.0% of cases in which the hypodermis was affected (10 cases)., Conclusions: In general, these findings are in agreement with results published in the literature, emphasizing the frequent finding of eosinophils unrelated to drug use, panniculitis and the rare association with Hodgkin's lymphoma. This is the fifth report of an association between Sweet's syndrome and Hodgkin's disease.

Background: Alpha-v-beta3 integrin (alphavbeta3) is a vitronectin ligand and plays an important role in melanoma progression., Objectives: The purpose of the study was to evaluate the expression of alphavbeta3 in superficial spreading cutaneous melanoma, in both conventional and tissue microarray (TMA) paraffin-embedded-tissue specimens, and correlate with histopathological variables and patient survival., Material and Methods: A total of 159 tissue samples from compound nevi (n = 19), in situ melanoma (n = 5), thin melanoma (n = 34), thick melanoma (n = 72) and metastatic melanoma (n = 29) were studied., Results: Compound nevus epithelioid cells had a mild expression of alphavbeta3. In situ melanoma cells had the highest expression among all specimens, when compared to nevi (p = 0.0000) and to invasive melanoma (p = 0.0003). Expression of alphavbeta3 did not differ according to depth of invasion or did it increase in metastatic cells., Conclusion: Our results suggested that alphavbeta3 integrin might have no impact on melanoma behavior. However, high levels of alphavbeta3-integrin expression for in situ melanoma may be related to pre-invasive phenotype with marked potential to invade.