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Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE).

AbstractObjective:In this study, we aimed to determine the role of Psidium cattleianumextract (PCE) and compare its effects with those of metformin (Met) in an animal model with type 2 diabetes mellitus (T2DM).Methods:T2DM was induced in rats using a high-fat diet (HFD), followed by a single dose of streptozotocin (STZ). Met and PCE were administered intragastrically once a day throughout the experiment, and their effects on biochemical, inflammatory, oxidative, and histological parameters were evaluated.Results:Met and PCE prevented the increase in serum levels of glucose, total cholesterol (TC), triacylglycerol (TG), very low-density lipoprotein (VLDL) and interleukin-6 (IL-6) induced by T2DM, and restored redox homeostasis in the liver and brain. Met increased the serum levels of anti-inflammatory cytokine and interleukin-10 (IL-10). Furthermore, both treatments restored the liver and pancreas from marked cellular disorganisation, vacuolisation, and necrosis, with PCE being more effective than Met in recovering histological changes.Conclusion:PCE is a promising agent for the prevention of T2DM complications.

Introduction:Distinguishing scarring (SA) versus non-scarring alopecia (NSA) may not be a simple procedure on either clinical or histopathological views. Aims:We sought to study the interobserver variability in the histopathological assessment of SA versus NSA, including clinical-pathological considerations. Methods:Two dermatopathologists independently interpreted the same set of 100 specimens (89 patients). The samples were serial sectioned and stained by hematoxylin and eosin and Verhöeff methods. The patients’ mean age was 46 years, with 13 being males and 76 females. Results:In 16/100 samples, there was no consensus among the two examiners regarding SA versus NSA (weighted kappa = 0.6583; 95% CI); 3/16 patients were re-biopsied, and in the second sample, consensus was reached. In 76/89 patients, the anatomopathological examination was helpful in defining the SA versus NSA subtype. Of the 84 samples in which there was interobserver agreement, 4 which had been considered scarring in the routine pathological report were re-classified as non-scarring, whereas one biopsy, previously diagnosed as non-scarring, was now considered cicatricial due to the newly found areas of lichenoid inflammation in the infundibular epithelium. Discussion:The ideal scalp examination may require deep serial biopsy sectioning, elastic tissue stain, re-biopsy, and strict clinical-evolutive correlation.

There are several activated forms of macrophages: 2 main groups are designated M1 and M2. While M1 macrophages have proinflammatory, bactericidal, and phagocytic functions and are the dominant phenotype observed in the early stages of inflammation, M2 macrophages are involved in constructive processes such as tissue repair; they play a role in wound healing and are required for revascularization and re-epithelialization. Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytosis. Its pathogenesis is not well understood, but it is not considered a neoplastic entity. JXGs possibly appear as a reaction to a nonspecific injury such as trauma or viral infection, although a genetic predisposition has been suggested in some cases. Tissue damage leads to a histiocytic response. JXGs appear, evolve toward maturation, and then most of them spontaneously regress. Young JXGs are characterized by small macrophages scattered in the dermis, in apposition close to the epidermis. As the lesion matures, the number of foamy macrophages and Touton cells increases and other cell types such as plasma cells, lymphocytes, and polymorphs are observed. Regressing xanthogranulomas will show numerous spindle cells in Significant values are in bold.a storiform distribution, interstitial fibrosis, and few foamy and Touton cells. In this study, we studied the immunophenotypic profile of macrophages found in cutaneous JXGs according to their stage of maturation. We examined the skin biopsies from 25 patients; all were embedded in paraffin and stained with hematoxylin and eosin and for immunohistochemistry. Typically, all JXGs were positive for factor XIIIa and CD4, and were negative for CD1a. The following histiocyte markers were used: CD68, CD204, CD163, MAC387, and HAM56. Images were analyzed by Image J software; data were statistically evaluated by SAS 9.0 software. The cases showed a slight predominance of males and the preference of the JXGs for the axial skin. Lesions occupied the papillary and reticular dermis in 85% of the cases and extended to the subcutaneous fat in the remainder. Compared with mature and regressing JXGs, younger lesions had a higher density of M1 macrophages, stained with MAC387. This antibody labels the histiocytes that have recently arrived in the areas of inflammation. As the lesions matured, there was an overwhelming predominance of M2 macrophages. These cells tended to cluster against the epidermis, except in the 2 cases in phase of regression. This suggests that there is a cross-talk between the epidermis and macrophages and that receptors, cytokines, chemokines, and adhesion molecules may play a role in the development and evolution of JXGs. These results indicate that, for most of their life, JXGs are formed by repairing M2 macrophages and are not just an M1 macrophagic response to a local antigen. The process appears to be influenced by chemical-mediator epidermal-macrophage cross-talking, considering the tendency of these cells to accumulate against the dermoepidermal junction.

ABSTRACTObjective: Major depressive disorder is a debilitating and recurrent psychiatric disorder. Blueberries have several biological properties, including neuroprotective effects, through antioxidant and anti-inflammatory actions. The aim of this study was to evaluate the effect of blueberry extract on depressive-like behavior and lipopolysaccharide (LPS)-induced neurochemical changes. Methods: Mice were pretreated with vehicle, fluoxetine (20 mg/kg) or blueberry extract (100 or 200 mg/kg) intragastrically for seven days before intraperitoneal LPS (0.83 mg/kg) injection. Twenty-four hours after LPS administration, mice were submitted to behavioral tests. Oxidative stress and neuroinflammatory parameters were evaluated in the cerebral cortex, hippocampus, and striatum. Results: Our data showed that blueberry extract or fluoxetine treatment protected against LPS-induced depressive-like behavior in tail suspension and splash tests (P < 0.05), without changes in locomotor activity (P > 0.05). LPS induced an increase in the levels of reactive oxygen species (P < 0.001), nitrite (P < 0.05) and thiobarbituric acid reactive substances (P < 0.01), as well as a reduction in total sulfhydryl content (P < 0.05) and catalase activity (P < 0.05) in brain structures; blueberry extract restored these alterations (P < 0.05). In addition, blueberry extract attenuated the increase in tumor necrosis factor-alpha (TNF-α) levels induced by LPS administration (P < 0.05). Conclusion: This study showed that blueberry extract exerted antidepressant-like effects, protected the brain against oxidative damage, and modulated TNF-α levels induced by LPS.

Abstract: Transdermal administration of raloxifene hydrochloride (RLX)-loaded nanostructured lipid carriers (NLCs) has been proposed to circumvent its low oral bioavailability (2%). Preformulation studies were carried out to evaluate drug-excipient compatibility of various adjuvants commonly used for NLC preparation (waxes, cholesterol, compritol, gelucire, span 60, span 80, span 85, tween 80, poloxamer 188, oleic acid, caprylic/capric triglyceride, and castor oil). It was used differential scanning calorimetry (DSC), isothermal stress testing (IST), and solubility studies. The most promising excipients were chosen for NLC obtention, and full characterization was done, including in vitro skin permeation. DSC curves suggested drug-excipient interaction among some compounds, and the IST study showed incompatibility of RLX with waxes, compritol, cholesterol, span 60, and poloxamer 188. Solubility studies helped select gelucire, caprylic/capric triglyceride, span 80, and tween 80 for NLC production. Twelve NLCs were obtained (NLC1 to NLC12), but NLC7 and NLC8 were the most promising ones. In vitro release studies demonstrated that NLC7 and NLC8 were able to control RLX release (14.74 and 9.07% at 24 h, respectively) compared with the unloaded drug (> 90% at 24 h). Unloaded RLX did not permeate the diffusion cells’ receptor medium and showed higher drug skin retention (11-fold) than RLX-loaded NLC. NLC reduced RLX skin retention, favoring drug permeation to deeper skin layers. NLC7 increased drug flux is 2.4-fold. NLC7 is a promising formulation for RLX transdermal drug delivery. Graphical abstract:

Studying biofilm dispersal is important to prevent Listeria monocytogenespersistence in food processing plants and to avoid finished product contamination. Reactive oxygen and nitrogen intermediates (ROI and RNI, respectively) may trigger cell detachment from many bacterial species biofilms, but their roles in L. monocytogenesbiofilms have not been fully investigated. This study reports on ROI and RNI quantification in Listeria monocytogenesbiofilms formed on stainless steel and glass surfaces; bacterial culture and microscopy combined with fluorescent staining were employed. Nitric oxide (NO) donor and inhibitor putative effects on L. monocytogenesdispersal from biofilms were evaluated, and transcription of genes (prfA, lmo 0990, lmo 0807, and lmo1485) involved in ROI and RNI stress responses were quantified by real-time PCR (qPCR). Microscopy detected the reactive intermediates NO, peroxynitrite, H2O2, and superoxide in L. monocytogenesbiofilms. Neither NO donor nor inhibitors interfered in L. monocytogenesgrowth and gene expression, except for lmo0990, which was downregulated. In conclusion, ROI and RNI did not exert dispersive effects on L. monocytogenesbiofilms, indicating that this pathogen has a tight control for protection against oxidative and nitrosative stresses.

The pathogenic bacterium Listeria monocytogenescan persist in food processing plants for many years, even when appropriate hygienic measures are in place, with potential for contaminating ready-to-eat products and, its ability to form biofilms on abiotic surfaces certainly contributes for the environmental persistence. In this research, L. monocytogeneswas grown in biofilms up 8 days attached to stainless steel and glass surfaces, contributing for advancing the knowledge on architecture of mature biofilms, since many literature studies carried out on this topic considered only early stages of cell adhesion. In this study, biofilm populations of two strains of L. monocytogenes(serotypes 1/2a and 4b) on stainless steel coupons and glass were examined using regular fluorescence microscopy, confocal laser scanning microscopy and classic culture method. The biofilms formed were not very dense and microscopic observations revealed uneven biofilm structures, with presence of exopolymeric matrix surrounding single cells, small aggregates and microcolonies, in a honeycomb-like arrangement. Moreover, planktonic population of L. monocytogenes(present in broth media covering the abiotic surface) remained stable throughout the incubation time, which indicates an efficient dispersal mechanism, since the culture medium was replaced daily. In conclusion, even if these strains of L. monocytogeneswere not able to form thick multilayer biofilms, it was noticeable their high persistence on abiotic surfaces, reinforcing the need to focus on measures to avoid biofilm formation, instead of trying to eradicate mature biofilms.

New techniques for tissue engineering (TE) are rapidly emerging. The basic concept of autologous TE is to isolate cells from small biopsy specimens, and to expand these cells in culture for subsequent seeding onto biodegradable scaffolds. Nanocrystalline diamond films have attracted the attention of researchers from a variety of different areas in recent years, due to their unique and exceptional properties. In this approach, human dental stem cells (hDSCs) were characterized by flow cytometry and grown on diamond films with hydrogen (H)-terminated and oxygen (O)-terminated surfaces for 28 days, and then removed by lysis and washing with distilled water. Energy dispersive spectroscopy analysis was performed, showing that the regions with O-terminated surfaces contained much higher levels of deposited calcium, oxygen, and phosphorus. These results suggest that the extracellular matrix was considerably more developed in the O-terminated regions, as compared with the H-terminated regions. In addition, optical microscopy of hDSCs cultured on the diamond substrate with H- and O-terminated surfaces, before washing with distilled water, showed preferential directions of the cells arrangement, where orthogonal lines suggest that the cells appeared to be following the O-terminated regions or hydrophilic surface. These findings suggest that O-terminated diamond surfaces prepared on biodegradable scaffolds can be useful for mineralized dental tissue formation.

Background & Purpose:Severe headache is a hallmark of spontaneous subarachnoid hemorrhage (SAH), affecting nearly 90% of patients during index hospitalization. In addition, up to 25% of SAH-survivors experience chronic headaches. Despite its high prevalence, means of management of headaches are limited, largely reliant on opioids, and often ineffective. Urgent efforts to reduce opioid use require innovative treatment strategies for the management of post-SAH headaches.Methods:This is a retrospective cohort comprising 12 adults who received bilateral pterygopalatine fossa (PPF) blockade from 9/2018 to 3/2021 for refractory headaches after spontaneous SAH. We examined pain scores, analgesic requirements and transcranial doppler ultrasound (TCD) parameters before and after the block placement. Descriptive statistics were calculated for all variables.Results:Twelve patients (mean age 54 years, 66% females, nine aneurysmal and three non-aneurysmal SAH) received PPF-block on post-bleed day 2 to 11 (median 6.5) during hospitalization in the neurointensive care unit. Hunt and Hess scores ranged from 1-3. Pain scale scores from 24-hour period before the block (8.8 ±1.4; mean, SD) decreased significantly to a mean of 5.1 (SD ± 3.0) until 20 hours post-block (p = 0.0156). Opioid use also decreased significantly from median (range) oral morphine equivalent dose (mg) administered in the 24h before the block of 22.5 (0-75) vs. 7.5 (0-45) after PPF-block (p=0.0391). Five (41%) patients had radiographic (but not clinical) vasospasm by TCD criteria before PPF-block; in four of these patients, TCD velocities improved on the day after PPF-block, in one patient velocities were increased on the day after PPF-block. The block was well tolerated with no adverse events of bleeding, infection, pain, or numbness at the injection site.Conclusion:These results demonstrate that PPF-blockade might be a promising alternative for managing post-SAH headaches. Further prospective controlled randomized powered to address the safety and efficacy of the PPF-block are warranted.

Nitrous oxide is an inhaling gas that can increase intratympanic pressure during the anesthetic act and cause negative pressure after it is discontinued, mainly in patients with Eustachian tube dysfunction. These pressure variations may come up with clinical implications such as tympanic membrane rupture, ossicular system disarticulation, haemotympanum, barotraumas, prosthesis displacement stapaedotomy and tympanic graft lateralization after tympanoplasty, in addition to serous fluid entrance into the middle ear during the negative pressure phase. Aim: To evaluate the nitrous oxide influence on the middle ear pressure in a population without tube malfunction performing pre and postoperative tympanometry. Study design: Transversal cohort. Material and Method: A prospective study was carried out with Universitário Clementino Fraga Filho Hospital- UFRJ inpatients submitted to general anesthesia with the use of 50% nitrous oxide from April to June 2003. It was also evaluated whether the duration of surgery, associated anesthetics, presence of allergic rhinitis and nasal septal deviation could contribute to the onset of intratympanic pressure alteration. Results: The sample was made up of 50 patients and in almost half of them (48%), postoperative tympanometry alterations (type C curve) were found when comparing to preoperative tympanometric control (type A curve). Neither gender nor age interfered in the onset of postoperative tympanometry alterations, similarly to surgery duration. The associated volatile anesthetic type, nasal septal deviation and allergic rhinitis were not able to influence postoperative middle ear pressure. Conclusion: Nitrous oxide modifies intratympanic pressure during the anesthetic act and after its discontinuation.

An 18-year-old man reported rapid decrease of visual acuity that progressed to total blindness in 1 month. Computed tomographic scanning showed two neoplastic masses: a large one, intra- and suprasellar, and a smaller cerebellar nodule. Histologically, the former proved to be a large metastasis of the small cerebellar medulloblastoma, which infiltrated and compressed the chiasm. Direct compression of the optic pathways by metastasis of a medulloblastoma is a rare event.

BACKGROUND: Because of their size and the possibility of complications, giant hemangiomas represent a therapeutic challenge. Various forms of treatment have been used, with variable results, including surgery, embolization, lasers, pentoxifylline, and corticosteroids. Interferon alfa has been used successfully to treat life-threatening hemangiomas, possibly by means of its antiangiogengenic activity. OBSERVATIONS: We treated 7 infants with organ-interfering and/or life-threatening giant hemangiomas with subcutaneous injections of 3 million U/m2 per day of interferon alfa-2b during the first month and subsequently every 48 to 72 hours, depending on the evolution in each case. The treatment lasted from 3 to 12 months. In 2 patients, interferon alfa-2b was administered while prednisone therapy was being tapered. In all 7 patients, there was considerable reduction of the volume of the hemangiomas and remission of their complications. All patients presented with fever, neutropenia, and an increase in serum aminotransferase levels. The patients who received interferon alfa-2b and prednisone seemed to improve at a faster rate. CONCLUSIONS: Interferon alfa-2b is a good option for the treatment of patients with steroid-resistant, organ-interfering and/or life-threatening giant hemangiomas. In our experience, the adverse effects were transient and minor and did not require the interruption of the treatment.Arch Dermatol. 1997;133:1567-1571

POEMS is an acronym that stands for a multisystem disorder that includes progressive sensorimotor Polyneuropathy, Organomegaly, Endocrinopathy, an M component in blood and/or concentrated urine, and Skin changes. The morphology of the peripheral nerves was mentioned in some of these cases and ranged from normal to those with segmental demyelination and/or degeneration of myelinated axons. We analyzed quantitatively the sural nerves of two cases of POEMS syndrome. Both nerves showed a severe loss of myelinated fibers, with a minor degree of regeneration. Degeneration of unmyelinated axons was observed, but to a lesser degree. There was marked collagen deposition in the endoneurium. The pathogenesis of the changes in the peripheral nerves and other organs in POEMS syndrome is still to be elucidated.

"Trench foot" is a particular risk for those involved in adventure tourism, for soldiers in winter mountain training exercises, and for the homeless. Nonfreezing cold nerve injury is characterized by axonal degeneration, which is attributed to free radicals released during cycles of ischemia and reperfusion. This pilot study sought to determine whether the administration of antioxidants might prevent or ameliorate the development of cold nerve injury. Twenty-six rats were divided into two groups. Group 1 animals received, by gavage, a mixture of vitamin C (150 mg/kg/d), vitamin E (100 mg/kg/d), and N-acetyl-L-cysteine (250 mg/kg/d) daily for 4 weeks. Allopurinol (20 mg/kg/d) was added in the last 4 days of treatment. Group 2 animals served as controls and did not receive any antioxidant supplements. After 1 month, two cycles of sciatic nerve cooling (0 degrees C) were induced in 10 controls and 10 experimental animals using circulating water through a nerve cuff. Six additional control animals were subjected to surgery but did not undergo nerve cooling. All animals were killed on the third postoperative day, and their nerves were processed for ultrastructural and quantitative studies. The proportion of degenerated myelinated and unmyelinated axons showed no significant difference between treated and untreated animals. We conclude that the administration of commonly used antioxidants does not prevent cold nerve injury.

A rare case of cavernous angioma of the dura mater at the convexity is presented. In comparison with the more common cavernous hemangiomas that arise from dural sinuses, the ones on the convexity have a much better prognosis. They do not seem to be associated with spontaneous hemorrhage, their removal is simpler and, transoperatory bleeding, if it occurs, is scanty. Computerized tomography detects the presence of cavernous angiomas of the convexity in only 70% of the cases, magnetic resonance imaging in 100%.

The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed, and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoniex vivoand in a murine model of schistosomiasis.

Schistosomiasis is a parasitic flatworm disease that infects over 200 million people worldwide, especially in poor communities. Treatment and control of the disease rely on just one drug, praziquantel.