Role of histopathological, serological and molecular findings for the early diagnosis of treatment failure in leprosy.

BACKGROUND: Treatment failure (TF) in leprosy following multidrug therapy (MDT) presents a significant challenge. The current World Health Organization (WHO) fixed-duration MDT regimen, based on lesion count, might not be adequate. Leprosy lacks clear-cut objective cure criteria, and the predictive value of post-MDT histopathological findings remains uncertain. This study aims to identify predictive factors for TF among leprosy patients who have completed the WHO-recommended MDT. METHODS: An analysis was conducted on 80 individuals from a national leprosy reference center, comprising 40 TF cases (with a mean relapse at 13.0 months) and 40 controls (with a mean of 113.1 months without disease signs). Various epidemiological and clinical-laboratory parameters were assessed post-MDT. RESULTS: In skin samples, the presence of foamy granuloma (OR = 7.36; 95%CI2.20-24.60; p = 0.0012) and histological bacillary index (hBI) ≥ 1+ (OR = 1.55; 95%CI1. 22-1.99; p = 0.0004) were significantly associated with TF, with odds ratios of 7.36 and 1.55, respectively. Individuals who experienced TF had a mean hBI of 3.02+ (SD ± 2.02), while the control group exhibited a mean hBI of 1.8+ (SD ± 1.88). An hBI ≥ 3 + showed a sensitivity of 73% and a specificity of 78% for TF detection (AUC: 0.75; p = 0.0001). Other histopathological features like epithelioid granulomas, and skin changes did not show significant associations (p > 0.05). Additionally, higher anti-phenolic glycolipid-I (anti-PGL-I) ELISA index (EI) levels were linked to a 1.4-fold increased likelihood for TF (OR = 1.4; 95%CI1.13-1.74; p = 0.0019). A mean EI of 4.48 (SD ± 2.80) was observed, with an EI ≥ 3.95 showing a sensitivity of 79% and a specificity of 59% for TF detection (AUC: 0.74; p = 0.0001). Moreover, the presence of Mycobacterium leprae (M. leprae) DNA in real-time polymerase chain reaction (qPCR) was associated with a 3.43-fold higher likelihood of TF. Multivariate regression analysis indicated that concurrent presentation of neural/perineural lymphocytic infiltrate, foamy granuloma, hBI ≥ 1+, and EI ≥ 1 markedly increased the likelihood of TF by up to 95.41%. CONCLUSION: Persistence of nerve-selective lymphocytic infiltrate, foamy granulomas, and bacilli in skin biopsies, and elevated EI post-MDT, may serve as predictive factors for identifying individuals at higher probability of TF.

Unveiling inflammatory biomarkers in multibacillary leprosy: the role of lymphocyte-platelet ratio in predicting leprosy reactions.

Leprosy is a neglected contagious disease that causes physical disability and episodes of inflammation, called leprosy reactions. There are currently no consolidated laboratory markers that can predict or confirm the diagnosis of leprosy reactions, negatively impacting the progression of the disease. The aim of this study was to analyze the behavior of inflammatory biomarkers in a population of patients with multibacillary leprosy. This prospective study in a northeastern capital involved 67 new cases of multibacillary leprosy, assessing inflammatory biomarkers at diagnosis. Histopathology, qPCR, slit skin smear microscopy, and laboratory tests, including CRP-albumin, neutrophil-lymphocyte, lymphocyte-monocyte, platelet-lymphocyte ratios, and systemic immune-inflammation index, were conducted. Statistical analysis utilized Stata version 16.0®, employing Chi-square, Kruskal-Wallis, and Poisson regression (5% significance). The population, mainly young brown men with low socioeconomic status, borderline leprosy, and and degree of physical disability one, saw 19.4% experiencing leprosy reactions. Standard multibacillary multidrug therapy was administered to all. Ratios and index values exceeding medians were prevalent (46.3-47.8%). Assessing biological markers against leprosy reactions revealed a positive relation between reactions and lymphocyte-platelet ratio (p = 0.05) and a positive trend with the systemic immune-inflammation index (p = 0.06). Patients with reactions were 1.3 times more likely to exhibit an elevated lymphocyte-platelet ratio. The lymphocyte-platelet ratio emerged as a potential indicator for recognizing leprosy reactions. Further research is essential to validate these findings, aiming for earlier detection of leprosy reactions.

Defensive Behavior and Integumentary Morphology of the Hairy Dwarf Porcupine Coendou spinosus (Rodentia: Erethizontidae).

New World porcupines (Erethizontidae) exhibit behaviors and possess integumentary structures, including the quills, that are used for self-defense. The North American porcupine (Erethizon dorsatum) has been well studied regarding these features; however, information is lacking for the South American Coendou species. We describe the defensive behavior and integumentary morphology of Coendou spinosus to understand the defensive strategies of this species and to compare with those reported for other species. We assessed the behaviors related to warning, defense, and escape of eight porcupines, as well as the characteristics of their pelage and quills. Furthermore, we microscopically analyzed skin samples of a roadkill adult male specimen. Similar to E. dorsatum, C. spinosus exhibited omnidirectional quill erection, revealing an aposematic color and, with their backs toward the perceived human threat, they performed quick tail and body movements to strike the hands of the human trying to capture them by the tail. Furthermore, C. spinosus presented an integumentary structure similar to that of E. dorsatum, and mechanisms to facilitate quill release when touched, penetration, and fixation in the opponent. The most distinct warning behavior noted was the vibration of the quills, which has not been reported for Erethizon. Our study confirms that, like other erethizontids, C. spinosus does not attack but exhibits warning, defense, and escape mechanisms and behaviors when threatened or touched. The dissemination of such information helps to counter the negative stigma associated with porcupines, as they can be the victims of attacks by dogs and humans, and to promote their conservation.

Effects of ozone therapy applied topically, by bagging, or both on the healing of clean wounds induced in rat's skin.

PURPOSE: This study aimed to evaluate the effects of ozone therapy applied topically and/or by bagging on the healing of clean wounds induced in rat's skin. METHODS: One hundred and twenty male rats of about 16 weeks old was divided into five groups: G1) saline solution (0.9%); G2) sunflower oil; G3) ozonated sunflower oil; G4) ozone bagging; G5) association of ozonated sunflower oil and ozone bagging. The wounds were evaluated through macroscopic, morphometric, histopathologic, and tensile strength analyses. RESULTS: Analysis among groups showed a lower percentage of wound contraction in G1 compared to G4 only in M7D. The tensile strength of the wounds showed differences among groups in the seventh (M7D) and the 14th (M14D) postoperative day, and among time points in G1 (M14D > M7D). The elongation of the wounds showed differences in G3 (M7D > M14D). Histological evaluation of the wounds showed significant change in bleeding, mixed to mononuclear infiltrate, congestion, and tissue disorganization for tissue organization between groups and time points. CONCLUSIONS: Ozone therapy applied topically and/or by bagging was not deleterious to the healing of clean wounds induced in rat's skin, but ozone bagging showed the best contribution to the healing process.

Development and evaluation of nanostructured systems for cutaneous delivery of H2S-releasing corticosteroids for skin inflammatory diseases.

Psoriasis is an immune-mediated chronic inflammatory disease that causes major psychosocial impact. Topical corticosteroids represent the standard pharmacological treatment for mild-to-moderate disease, but their local and systemic adverse effects reinforce the need for treatment innovations. Here we developed lamellar phase-based formulations for topical delivery of a hybrid dexamethasone and hydrogen sulfide (H2S) donor molecule (Dexa-TBZ), aiming to potentiate the effects of the glucocorticoid with H2S. They offer the possibility to obtain precursor formulations free of water that originate lamellar phases upon water addition, preventing drug hydrolysis during storage. Two groups of formulations were developed varying the surfactants and oil phase types and content. Systems containing 20 and 70 % of water formed, respectively, bulk lamellar phase and a more fluid formulation consisting of dispersed droplets (< 1000 nm) stabilized by lamellar phase. Both presented pseudoplastic behavior. Dexa-TBZ was incorporated at 1 %, remaining stable for 8 h. Drug content decreased to ∼80 % after 1 week in precursor formulations free of water, but remained stable after that. Without causing changes to the cutaneous barrier function ex vivo or to the histological structure of the skin in vivo, the formulation containing phosphatidylcholine as surfactant and 70 % of water promoted 1.8- and 2.7-fold increases in Dexa-TBZ penetration in the stratum corneum and epidermis+dermis, respectively, compared to a control solution, demonstrating their potential applicability as topical delivery systems.

Pseudoalteromonas simplex sp. nov. Isolated from the Skin of Bandtail Puffer Fish (Sphoeroides spengleri).

A novel bacterial isolate A520T (A520T = CBAS 737T = CAIM 1944T) was obtained from the skin of bandtail puffer fish Sphoeroides spengleri (Tetraodontidae Family), collected in Arraial do Cabo (Rio de Janeiro, Brazil). A520T is Gram-stain-negative, flagellated and aerobic bacteria. Optimum growth occurs at 25-30 °C in the presence of 3% NaCl. The genome sequence of the novel isolate consisted of 4.5 Mb (4082 coding genes and G+C content of 41.1%). The closest phylogenetic neighbor was Pseudoalteromonas shioyasakiensis JCM 18891T (97.9% 16S rRNA sequence similarity, 94.8% Average Amino Acid Identity, 93% Average Nucleotide Identity and 51.8% similarity in Genome-to-Genome-Distance). Several in silico phenotypic features are useful to differentiate A520T from its closest phylogenetic neighbors, including trehalose, D-mannose, cellobiose, pyrrolidonyl-beta-naphthylamide, starch hydrolysis, D-xylose, lactose, tartrate utilization, sucrose, citrate, glycerol, mucate and acetate utilization, malonate, glucose oxidizer, gas from glucose, nitrite to gas, L-rhamnose, ornithine decarboxylase, lysine decarboxylase and yellow pigment. The genome of the novel species contains 3 gene clusters (~ 66.81 Kbp in total) coding for different types of bioactive compounds that could indicate ecological roles pertaining to the bandtail puffer fish host. Based on genome-based taxonomic approach, strain A520T (A520T = CBAS 737T = CAIM 1944T) is proposed as a new species, Pseudoalteromonas simplex sp. nov.

Erythema nodosum as an atypical dermatological manifestation of HTLV-1 infection: A case report and literature review.

Human T-lymphotropic virus 1 (HTLV-1) is the etiological agent of several pathologies, and some of them are not investigated, resulting in a lack of literature that impacts the correct diagnosis. Skin manifestations, such as HTLV-1-associated infectious dermatitis (IDH), are common in patients living with HTLV-1 but could not be the only one. Here, we report for the first time a patient infected with HTLV-1, without previous diagnosis of HTLV-1-related diseases, presenting erythema nodosum (EN). Given the patient's long-term asymptomatic carrier status, the emergence of EN underscores the importance of considering HTLV-1 in the differential diagnosis when encountering EN, especially in endemic regions.

Production and Characterization of Electrospun Chitosan, Nanochitosan and Hyaluronic Acid Membranes for Skin Wound Healing.

The development of new wound dressings made from biomaterials, which offer a better cost-benefit ratio and accelerate the healing process, is increasing nowadays. Various biopolymers can be electrospun to form functional membranes for wound healing. Therefore, in this study, chitosan and nanochitosan membranes with or without hyaluronic acid were prepared using the electrospinning technique, characterized and evaluated in the healing of skin wounds in rats. Chitosan and nanochitosan solutions, with or without hyaluronic acid, were prepared at concentrations of 1%-4% using PEO (polyethylene oxide) and subjected to the electrospinning process to obtain membranes characterized by scanning electron microscopy (SEM), mechanical tests, and antimicrobial activity. The healing effect of the membranes was evaluated by monitoring the area of the lesions, contraction of the wounds, histologic analysis, and induction of pro-inflammatory cytokine (IL-1 α and TNF-α) production in rats. The nanochitosan and nanochitosan membranes with hyaluronic acid achieved greater fiber diameter and uniformity, resistance, elasticity, and thermal stability, in addition to good adhesion to the wound bed and permeation capacity. Despite not presenting antimicrobial activity in vitro, they contributed to the production of pro-inflammatory interleukins in the animals tested, provided physical protection, reduced the wound area more markedly until the seventh day of the evaluation, with an acceleration of the healing process and especially when functionalized with hyaluronic acid. These results indicate that the membranes may be promising for accelerating the healing process of chronic wounds in humans.

Evaluation of nasogastric tube fixation methods: adhesion, displacement and skin integrity.

OBJECTIVE: to evaluate three methods of nasogastric tube fixation in terms of adhesion, displacement and skin integrity. METHOD: ex vivo study, with a sample of 30 experimental noses (10 for each type of fixation), developed with porcine skin, based on the average measurements of the human nose, in which 14-gauge polyvinyl chloride probes were inserted and 2 methods of fixation with adhesive tape (Fixation A and B) and one with an industrial device (Fixation C) were used. Each group was exposed to traction of 50, 100 and 500g sequentially over 12 and 24 hours, testing: adhesion capacity, probe displacement and skin integrity. The Chi-square test of independence was calculated for nominal variables and Student's t-tests and analysis of variance (p< 0.05) for rational variables. RESULTS: fixation B showed lower adhesion capacity (p <0.001) when compared to the other two fixations. A mean displacement of 52.17 mm was observed in the probes fixed by methods A and B and a greater occurrence of lesions associated with fixations A and C (p = 0.001). CONCLUSION: the results show complications related to the fixations: lack of adhesion, displacement of the probe and skin lesions, drawing attention to the complexity of the procedure.

Evaluation of enteral and parenteral hyaluronic acid in induced ischemic skin flaps in rats: a double-blinded and randomized study.

PURPOSE: To evaluate exogenous hyaluronic acid (HA) derived from bacterial fermentation through enteral and parenteral routes in ischemic skin flaps induced in rats, using clinical and histological exams; and interleukins (IL) as tissue inflammatory biomarkers. METHODS: Sixty-four male adults Wistar rats with ischemic skin flaps on the dorsum were randomized into four groups, based on the treatment protocol: subcutaneous administration of saline solution (0.9%) (GI); oral administration of distilled water (GII); subcutaneous administration of HA (0.3%) (GIII); and oral administration of HA (1%) (GIV). Flaps of all groups were comparable regarding clinical and macroscopic evaluation, histological examination, pro-inflammatory cytokines (IL-1ß, IL-6, and tumor necrosis factor-α) and anti-inflammatory cytokine IL-10. RESULTS: A lower percentage of necrosis was identified in flaps treated with subcutaneous administration of HA (0.3%). The pro- and anti-inflammatory cytokines, epidermis thickness, blood vessels, and inflammatory cells showed statistically significant inter-group and intra-group differences (p < 0.05). CONCLUSIONS: High molecular HA (1,400 ~ 2,000 kDa) administrated by subcutaneous or oral route exhibited beneficial effects in ischemic skin flaps of rats. However, subcutaneous administration of HA (0.3%) showed better results in terms of the percentage of necrosis and epithelialization.

Evaluation of the photothermal effects of the subdermal high-power laser in the skin of an experimental rat model.

The aim of the present study was to evaluate the photothermal effects of a subdermal high-power diode laser at a wavelength (λ) of 1470 nm in the skin of rats. Twenty male Wistar rats were used, divided into 2 groups: placebo laser (PL) and active laser (AL). A high-power diode laser equipment was applied to 5 subdermal vectors on the animal's back region. The results demonstrated that active laser animals showed a better arrangement of collagen fiber bands, an increase in the thickness of the dermis and the number of vessels. Furthermore, animals treated with active laser showed an increased immunoexpression of TGF-ß and VEGF compared to the placebo. The present work demonstrated that the subdermal high-power diode laser increases the vascularization and the expression of factors that enhance skin regeneration and may be promising resource in the esthetic and dermatology clinical treatment of skin rejuvenation.

IL-17 in skin infections and homeostasis.

Interleukin (IL) 17 is a proinflammatory cytokine belonging to a structurally related group of cytokines known as the IL-17 family. It has been profoundly studied for its contribution to the pathology of autoimmune diseases. However, it also plays an important role in homeostasis and the defense against extracellular bacteria and fungi. IL-17 is important for epithelial barriers, including the skin, where some of its cellular targets reside. Most of the research work on IL-17 has focused on its effects in the skin within the context of autoimmune diseases or sterile inflammation, despite also having impact on other skin conditions. In recent years, studies on the role of IL-17 in the defense against skin pathogens and in the maintenance of skin homeostasis mediated by the microbiota have grown in importance. Here we review and discuss the cumulative evidence regarding the main contribution of IL-17 in the maintenance of skin integrity as well as its protective or pathogenic effects during some skin infections.

The GBA1 K198E Variant Is Associated with Suppression of Glucocerebrosidase Activity, Autophagy Impairment, Oxidative Stress, Mitochondrial Damage, and Apoptosis in Skin Fibroblasts.

Parkinson's disease (PD) is a multifactorial, chronic, and progressive neurodegenerative disorder inducing movement alterations as a result of the loss of dopaminergic (DAergic) neurons of the pars compacta in the substantia nigra and protein aggregates of alpha synuclein (α-Syn). Although its etiopathology agent has not yet been clearly established, environmental and genetic factors have been suggested as the major contributors to the disease. Mutations in the glucosidase beta acid 1 (GBA1) gene, which encodes the lysosomal glucosylceramidase (GCase) enzyme, are one of the major genetic risks for PD. We found that the GBA1 K198E fibroblasts but not WT fibroblasts showed reduced catalytic activity of heterozygous mutant GCase by -70% but its expression levels increased by 3.68-fold; increased the acidification of autophagy vacuoles (e.g., autophagosomes, lysosomes, and autolysosomes) by +1600%; augmented the expression of autophagosome protein Beclin-1 (+133%) and LC3-II (+750%), and lysosomal-autophagosome fusion protein LAMP-2 (+107%); increased the accumulation of lysosomes (+400%); decreased the mitochondrial membrane potential (∆Ψm) by -19% but the expression of Parkin protein remained unperturbed; increased the oxidized DJ-1Cys106-SOH by +900%, as evidence of oxidative stress; increased phosphorylated LRRK2 at Ser935 (+1050%) along with phosphorylated α-synuclein (α-Syn) at pathological residue Ser129 (+1200%); increased the executer apoptotic protein caspase 3 (cleaved caspase 3) by +733%. Although exposure of WT fibroblasts to environmental neutoxin rotenone (ROT, 1 µM) exacerbated the autophagy-lysosomal system, oxidative stress, and apoptosis markers, ROT moderately increased those markers in GBA1 K198E fibroblasts. We concluded that the K198E mutation endogenously primes skin fibroblasts toward autophagy dysfunction, OS, and apoptosis. Our findings suggest that the GBA1 K198E fibroblasts are biochemically and molecularly equivalent to the response of WT GBA1 fibroblasts exposed to ROT.

Medical Adhesive-Related Skin Injury at 10 Years: An Updated Consensus.

Awareness of medical adhesive-related skin injury (MARSI) has increased in the decade since a foundational consensus report was published in 2013. Additional research has provided greater knowledge of the epidemiology of MARSI, along with its assessment, prevention, and management. To summarize knowledge generated in the past decade and review our current understanding of MARSI, a panel of nine clinical experts from four countries (United States of America, United Kingdom, Canada, and Brazil) convened to discuss the literature published since the initial 2013 document and develop updated recommendations for clinical practice. The group formulated 20 updated consensus statements covering the assessment, prevention, and management of skin injuries related to adhesive medical devices and proposed next steps to address remaining gaps in research and knowledge of this complex and clinically relevant condition.

Effect of Royal Sun Medicinal Mushroom Agaricus brasiliensis KA21 (Agaricomycetes) Cultivated Outdoors on Wound Healing and Maintaining Skin Elasticity.

Royal sun medicinal mushroom Agaricus brasiliensis KA21 has various beneficial pharmacological effects; however, these effects are influenced by its cultivation conditions. A. brasiliensis KA21 is rich in ß-glucan, which promotes wound healing. This study evaluated the wound healing-promoting effects of A. brasiliensis KA21 and the influence of cultivation conditions on these effects. Upon evaluation of its effect on wound healing, the outdoor-cultivated A. brasiliensis KA21 (KAOD) promoted wound healing in mice, and the effect of KAOD was stronger than that of the indoor-cultivated one (KAID). In addition, A. brasiliensis KA21 promoted the synthesis of collagen I and III, which are involved in promoting wound healing; KAOD strongly induced collagen III production. Furthermore, KAOD suppressed the decrease in skin elasticity after acetone application in our mouse model, which was not observed for KAID. These results show that KAOD is useful as a supplement in surgery and injury healing for humans and animals, improving immunity against pathogens in wound areas and promoting wound healing. In addition, KAOD may be useful in the field of skin aesthetics for repairing skin damage and maintaining skin elasticity.

The Tiny Big Difference: Nanotechnology in Photoprotective Innovations - A Systematic Review.

UV radiation causes long- and short-term skin damage, such as erythema and skin cancer. Therefore, the use of sunscreens is extremely important. However, concerns about UV filter safety have prompted exploration into alternative solutions, with nanotechnology emerging as a promising avenue. This systematic review identified 23 experimental studies utilizing nanocarriers to encapsulate sunscreens with the aim of enhancing their efficacy and safety. Polymeric and lipid nanoparticles are frequently employed to encapsulate both organic and inorganic UV filters along with natural antioxidants. Nanocarriers have demonstrated benefits including reduced active ingredient usage, increased sun protection factor, and mitigated photoinstability. Notably, they also decreased the skin absorption of UV filters. In summary, nanocarriers represent a viable strategy for improving sunscreen formulations, offering enhanced physicochemical properties and bolstered photoprotective effects, thereby addressing concerns regarding UV filter safety and efficacy in cosmetic applications.

Effect of iontophoresis on dacarbazine cutaneous delivery for melanoma topical treatment.

Dacarbazine (DTIC) is the drug of choice for melanoma treatment, but its systemic administration is related to several adverse effects. Here, DTIC topical delivery stimulated by iontophoresis is proposed to overcome such drawbacks. Hence, this work analyzed the impact of anodal iontophoresis on DTIC cutaneous delivery to provide an innovative topical alternative for melanoma treatment. The electrical stability of the drug was evaluated prior to the iontophoretic experiments, which demonstrated the need to add an antioxidant to the drug formulation. DTIC cutaneous permeation was evaluated in vitro for 6 h using three current densities (0.10, 0.25, and 0.50 mA/cm2). In addition, the effect of DTIC against skin cancer cells (MeWo and WM164) was investigated for 72 h of exposure to the drug. Iontophoresis stimulated skin drug permeation compared to the passive control. However, the antioxidant presence reduced DTIC permeation under the lower currents of 0.10 and 0.25 mA/cm2, which was compensated by increasing the current density to 0.50 mA/cm2. At 0.50 mA/cm2, iontophoresis enhanced topical cutaneous drug permeation 7-fold (p < 0.05) compared to the passive control. DTIC showed a concentration-dependent antiproliferative effect on melanoma cell lines. Thus, iontophoresis intensifies DTIC skin penetration in concentrations that can reduce cell viability and induce cell death. In conclusion, DTIC cutaneous delivery mediated by iontophoresis is a promising approach for treating melanomas and other skin tumors.

Characteristics of the Integument of Phyllomedusa burmeisteri (Anura, Phyllomedusidae) and Boana semilineata (Anura, Hylidae) Males Can Contribute to Understanding its Relation to Habitat.

The integument of anurans plays vital physiological roles, crucial for understanding the species' survival in their environment. Despite its significance, there are few studies describing the cutaneous morphology of anurans from the Brazilian Atlantic Forest. This study aimed to characterize the integument of Phyllomedusa burmeisteri and Boana semilineata in males using microscopic and histochemical approaches. Histological sections were stained with various dyes, and additional fragments underwent electron microscopy and energy-dispersive X-ray spectroscopy. Results showed different projections on the dorsal and ventral regions of males from these species, without the Eberth-Katschenko layer. Differences in the arrangement of chromatophore cells in regions with varying solar incidence were observed in the spongy dermis. Various gland types were identified, aiding taxonomic differentiation and validation of behavioral data. Both species had seromucous and granular glands, while only P. burmeisteri displayed lipid glands. Histochemical analysis revealed higher production of polysaccharides and proteins, contributing to the integument's moisture and protection. Lipid secretions in P. burmeisteri helped waterproof the integument more effectively against desiccation. This study concludes that analyzing anuran integument provides valuable insights into their behavior, with integument composition potentially influenced by habitat choice among different species.

Chondroitin Sulfate for Cartilage Regeneration, Administered Topically Using a Nanostructured Formulation.

In the pharmaceutical sector, solid lipid nanoparticles (SLN) are vital for drug delivery incorporating a lipid core. Chondroitin sulfate (CHON) is crucial for cartilage health. It is often used in osteoarthritis (OA) treatment. Due to conflicting results from clinical trials on CHON's efficacy in OA treatment, there has been a shift toward exploring effective topical systems utilizing nanotechnology. This study aimed to optimize a solid lipid nanoparticle formulation aiming to enhance CHON permeation for OA therapy. A 3 × 3 × 2 Design of these experiments determined the ideal parameters: a CHON concentration of 0.4 mg/mL, operating at 20,000 rpm speed, and processing for 10 min for SLN production. Transmission electron microscopy analysis confirmed the nanoparticles' spherical morphology, ensuring crucial uniformity for efficient drug delivery. Cell viability assessments showed no significant cytotoxicity within the tested parameters, indicating a safe profile for potential clinical application. The cell internalization assay indicates successful internalization at 1.5 h and 24 h post-treatment. Biopharmaceutical studies supported SLNs, indicating them to be effective CHON carriers through the skin, showcasing improved skin permeation and CHON retention compared to conventional methods. In summary, this study successfully optimized SLN formulation for efficient CHON transport through pig ear skin with no cellular toxicity, highlighting SLNs' potential as promising carriers to enhance CHON delivery in OA treatment and advance nanotechnology-based therapeutic strategies in pharmaceutical formulations.

VL-HIV co-infection with Leishmania containing skin lesions resembling para-kala-azar dermal leishmaniasis.

Leishmaniases are a group of neglected vector-borne infectious diseases that are among the six priority endemic diseases worldwide. Visceral leishmaniasis (VL) is the most severe clinical manifestation, characterized by systemic and chronic visceral involvement and high mortality in immunosuppressed and untreated patients. VL can be complicated into post-kala-azar dermal leishmaniasis (PKDL), and when dermatologic disorders occur simultaneously with active VL, an intermediate clinical form called para-kala-azar dermal leishmaniasis (para-KDL) occurs. This clinical form is of great epidemiological relevance, as humans act as a source of infection for vectorial transmission. In the Americas, Brazil is among the seven countries responsible for more than 90% of VL cases, though reports of PKDL and para-KDL are rare. This paper presents three cases of VL-HIV co-infection with Leishmania-containing skin lesions resembling para-kala-azar dermal leishmaniasis. The cases were investigated by the team from the Infectious Diseases Department of University Hospital (HUMAP/UFMS) in Mato Grosso do Sul, Brazil. The three patients exhibited skin lesions where amastigote forms of L. (L.) infantum were identified. All cases exhibited similar clinical manifestations of para-KDL, including fever, hepatosplenomegaly, pancytopenia, and disseminated skin lesions. The study described the prevalence of comorbidities, the incidence of VL relapse, and the therapeutic regimen in relation to the outcomes. The study underscores the importance of follow-up and secondary prophylaxis in patients with VL, which are essential for the efficacy of the treatment. Furthermore, the study provides insight into the potential epidemiological profile of para-KDL cases in Brazil, which contributes to the development of more efficient clinical management strategies for patients.