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Introduction: Conservative treatments such as physical therapies are usually the most indicated for the management of musculoskeletal pain; therefore, a detailed description of interventions enables the reproducibility of interventions in clinical practice and future research. The objective of this study is to evaluate the description of physical interventions for musculoskeletal pain in children and adolescents., Methods: We considered randomized controlled trials that included children and adolescents between 4 and 19 years old with acute or chronic/persistent musculoskeletal pain. We included physical therapies related to all types of physical modalities aimed at reducing the intensity of pain or disability in children and adolescents with musculoskeletal pain. The description of interventions was assessed using the Template for Intervention Description and Replication (TIDieR) checklist. We performed electronic searches in the following databases: CENTRAL, MEDLINE, EMBASE, CINAHL, PsyINFO and PEDro up to April 2024. The description of physical interventions was presented using frequencies, percentages and 95% confidence intervals (CIs) of the TIDieR checklist items described in each study. We also calculated the total TIDieR score for each study and presented these data as mean and standard deviation., Results: We included 17 randomized controlled trials. The description measured through the TIDieR checklist scored an average of 11 (5.2) points out of 24. The item of the TIDieR that was most described was item 1 (brief name) and most absent was item 10 (modifications)., Conclusion: The descriptions of physical interventions for the treatment of musculoskeletal pain in children and adolescents are partially described, indicating the need for strategies to improve the quality of description to enable true clinical reproducibility., (© 2024. The Author(s).)

Multifunctional therapies have emerged as innovative strategies in cancer treatment. In this research article, we proposed a nanostructured lipid carrier (NLC) designed for the topical treatment of cutaneous melanoma, which simultaneously delivers 5-FU and Bcl-2 siRNA. The characterized nanoparticles exhibited a diameter of 259 ± 9 nm and a polydispersion index of 0.2, indicating a uniform size distribution. The NLCs were primarily localized in the epidermis, effectively minimizing the systemic release of 5-FU across skin layers. The ex vivo skin model revealed the formation of a protective lipid film, decreasing the desquamation process of the stratum corneum which can be associated to an effect of increasing permeation. In vitro assays demonstrated that A375 melanoma cells exhibited a higher sensitivity to the treatment compared to non-cancerous cells, reflecting the expected difference in their metabolic rates. The uptake of NLC by A375 cells reached approximately 90% within 4 h. The efficacy of Bcl-2 knockdown was thoroughly assessed using ELISA, Western blot, and qRT-PCR analyses, revealing a significant knockdown and synergistic action of the NLC formulation containing 5-FU and Bcl-2 siRNA (at low concentration --100 pM). Notably, the silencing of Bcl-2 mRNA also impacted other members of the Bcl-2 protein family, including Mcl-1, Bcl-xl, BAX, and BAK. The observed modulation of these proteins strongly indicated the activation of the apoptosis pathway, suggesting a successful inhibition of melanoma growth and prevention of its in vitro spread., (© 2024. Controlled Release Society.)

The in vitro cultivation of M. leprae has not been possible since it was described as causing leprosy, and the limitation of animal models for clinical aspects makes studies on leprosy and bacteria-human host interaction a challenge. Our aim was to standardize the ex vivo skin model (hOSEC) to maintenance and study of M. leprae as an alternative animal model. Bacillary suspensions were inoculated into human skin explants and sustained in DMEM medium for 60 days. Explants were evaluated by RT-PCR-16SrRNA and cytokine gene expression. The viability and infectivity of bacilli recovered from explants (D28 and D60) were evaluated using the Shepard's model. All explants were RT-PCR-16SrRNA positive. The viability and infectivity of recovered bacilli from explants, analyzed after 5 months of inoculation in mice, showed an average positivity of 31%, with the highest positivity in the D28 groups (80%). Furthermore, our work showed different patterns in cytokine gene expression (TGF-β, IL-10, IL-8, and TNF-α) in the presence of alive or dead bacilli. Although changes can be made to improve future experiments, our results have demonstrated that it is possible to use the hOSEC to maintain M. leprae for 60 days, interacting with the host system, an important step in the development of experimental models for studies on the biology of the bacillus, its interactions, and drug susceptibility.

Background: Estimates of prevalence of musculoskeletal pain in children and adolescents vary considerably and the impact of pain on children's life is often not considered., Objective: To determine the one-month prevalence of disabling musculoskeletal pain in children and adolescents. The secondary aims are to: 1) determine the body region with the highest prevalence; 2) understand the characteristics of the children with disabling musculoskeletal pain; and 3) describe the parents' perception of the prevalence., Methods: This cross-sectional study was conducted in public and private schools in the states of São Paulo and Ceará, Brazil. Children self-reported presence and impact of pain, pain intensity, psychosomatic symptoms, and quality of life. Parents completed parent-proxy versions and perception of the child's sleep quality. Descriptive statistics were used to summarise the data., Results: A total of 2,688 children and adolescents were included in this study. The prevalence of disabling musculoskeletal pain in the previous month was 27.1%. The back was the region most often affected (51.8%). Children with disabling musculoskeletal pain were older, heavier, had worse relationships with their family, perceived their backpacks as heavy, carried their backpacks more with one shoulder, had more negative psychosomatic symptoms, had poorer quality of life, and had higher pain intensity. Parents tended to underestimate the presence of pain in their children., Conclusion: The one-month prevalence of activity limiting musculoskeletal pain in children and adolescents was 27.1% with the back being the most often affected body region. Parents tended to underestimate the presence of pain in their children., Competing Interests: Conflicts of interest All authors declare no conflict of interest., (Copyright © 2024 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Liquid crystalline nanoparticles (LCNs) are an attractive drugs topical delivery system due to the great internal ordering, wide interfacial area and structural similarities with the skin. In this work, LCNs were designed to encapsulate triptolide (TP) and to complex on its surface small interfering RNAs (siRNA) targeting TNF-α and IL-6, aiming at topical co-delivery and regulating multi-targets in psoriasis. These multifunctional LCNs showed appropriate physicochemical properties for topical application, such as a mean size of 150 nm, low polydispersion, TP encapsulation greater than 90% and efficient complexation with siRNA. The internal reverse hexagonal mesostructure of LCNs was confirmed by SAXS while their morphology was assessed by cryo-TEM. In vitro permeation studies revealed an increase of more than 20-fold in the distribution of TP through the porcine epidermis/dermis was achieved after the application of LCN-TP or LCN TP in hydrogel. In cell culture, LCNs showed good compatibility and rapid internalization, which was attributed to macropinocytosis and caveolin-mediated endocytosis. Anti-inflammatory potential of multifunctional LCNs was assessed by reducing of TNF-α, IL-6, IL-1β and TGF-β1 levels in LPS-stimulated macrophages. These results support the hypothesis that the co-delivery of TP and siRNAs by LCNs may be a new strategy for psoriasis topical therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The aim of this research was to evaluate the efficacy of a topical formulation containing chitosan-chamomile microparticles in cutaneous healing in rats. Method: Male Wistar rats (n=57) were randomly distributed into three groups: treatment; vehicle; and control. Evaluations were performed on days 2, 7 and 14 after the surgical procedure using skin lesion photography, and histological and biochemical analyses. Results: The results showed that there was no difference in the healing index and in the histological analysis of the inflammatory infiltrate among groups. Fibrogenesis was more significant in the group treated with the test formulation at day 7, and angiogenesis was greater in the vehicle and chamomile groups at day 2. The quantification of hydroxyproline showed a higher amount of collagen in the group treated with chamomile, mainly at day 14, although the histological quantification of collagen showed no difference between the groups. Conclusion: From the results of this study, it can be concluded that the formulation, although it had no effect on the healing time, improved the quality of the cicatricial tissue formed with a greater quantity of fibroblasts and collagen.

Introduction: Hansen's disease (HD) primarily infects peripheral nerves, with patients without HD being free of peripheral nerve damage. Household contacts (HHCs) of patients with HD are at a 5-10 times higher risk of HD than the general population. Neural thickening is one of the three cardinal signs that define a case of HD according to WHO guidelines, exclusively considering palpation examination that is subjective and may not detect the condition in the earliest cases even when performed by well-trained professionals. High-resolution ultrasound (HRUS) can evaluate most peripheral nerves, a validated technique with good reproducibility allowing detailed and accurate examination., Objective: This study aimed to use the peripheral nerve HRUS test according to the HD protocol as a diagnostic method for neuropathy comparing HHCs with healthy volunteers (HVs) and patients with HD., Methods: In municipalities from 14 different areas of Brazil we selected at random 83 HHC of MB-patients to be submitted to peripheral nerve ultrasound and compared to 49 HVs and 176 HD-patients., Results: Household contacts assessed by HRUS showed higher median and mean absolute peripheral nerve cross-sectional area (CSA) values and greater asymmetries (ΔCSA) compared to HVs at the same points. Median and mean absolute peripheral nerve CSA values were higher in patients with HD compared to HCCs at almost all points, while ΔCSA values were equal at all points. Mean ± SD focality (ΔTpT) values for HHCs and patients with HD, respectively, were 2.7 ± 2.2/2.6 ± 2.2 for the median nerve, 2.9 ± 2.7/3.3 ± 2.9 for the common fibular nerve ( p > 0.05), and 1.3 ± 1.3/2.2 ± 3.9 for the ulnar nerve ( p < 0.0001)., Discussion: Considering HRUS findings for HHCs, asymmetric multiple mononeuropathy signs (thickening or asymmetry) in at least 20% of the nerves evaluated could already indicates evidence of HD neuropathy. Thus, if more nerve points are assessed in HHCs (14 instead of 10), the contacts become more like patients with HD according to nerve thickening determined by HRUS, which should be a cutting-edge tool for an early diagnosis of leprosy cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Voltan, Marques-Júnior, Santana, Lincoln Silva, Leite, De Paula, Bernardes Filho, Barreto, Da Silva, Conde, Salgado and Frade.)

Establishing the first human presence on Mars will be the most technically challenging undertaking yet in the exploration beyond our planet. The remoteness of Mars from Earth, the inhospitable surface conditions including low atmospheric pressure and cold temperatures, and the need for basic resources including water, pose a formidable challenge to this endeavour. The intersection of multiple disciplines will be required to provide solutions for temporary and eventually permanent Martian habitation. This review considers the role cyanobacteria and eukaryotic microalgae (collectively referred to here as 'microalgae') may have in supporting missions to the red planet. The current research using these microorganisms in biological life support systems is discussed, with a systematic analysis of their usage in each system conducted. The potential of microalgae to provide astronauts with oxygen, food, bio-polymers and pharmaceuticals is considered. An overview of microalgal experiments in space missions across the last 60 years is presented, and the research exploring the technical challenges of cultivation on Mars is discussed. From these findings, an argument for culturing microalgae in subterranean bioreactors is proposed. Finally, future synthetic biology approaches for enhancing the cyanobacterial/microalgal role in supporting human deep-space exploration are presented. We show that microalgae hold significant promise for providing solutions to many problems faced by the first Martian settlers, however these can only be realised with significant infrastructure and a reliable power source., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Hansen's disease (HD) is the most common cause of treatable peripheral neuropathy in the world that may or may not involve skin manifestations, and physical examination based on simplified neurologic evaluation is a subjective and inaccurate procedure. High-resolution ultrasound (HRUS) can be used to evaluate peripheral nerves and is a validated technique of good reproducibility, permitting a detailed and precise examination., Objectives: We proposed to establish objective criteria for absolute values of the measurement of the CSA of peripheral nerves and their indices of the ΔCSA and ΔTpT in the diagnosis of Hansen's disease neuropathy as compared with healthy voluntaries., Materials and Methods: In municipalities from different regions of Brazil, we randomly selected 234 volunteer Brazilian patients diagnosed with leprosy to be submitted to peripheral nerve echography and compared with 49 healthy Brazilian volunteers., Results: Hansen Disease assessed by high resolution ultrasound is a primarily neural disease that leads to multiple hypertrophic mononeuropathy characterized by CSA values exceeding normal limits (Med CT = 10.2 mm 2 ; UT = 9.8 mm 2 ; UPT = 9.3 mm 2 ; CFFH = 18.3 mm 2 ; T = 9.6 mm 2 ), and the pattern of asymmetry (ΔCSA>2.5 mm 2 with RR 13) and focality (ΔTPT > 2.5 mm 2 with RR 6.4) of this thickening has higher sensitivity (76,1%) and specificity (87,8 %) for its early diagnosis that laboratory tests. Analyzing each subject, the percentage of thickened nerves detected among the total number of nerves assessed was higher among patients with HD than among healthy individuals ( p < 0.0001). Individuals with two or more thickened nerves were at 24.1 times higher relative risk (95% CI: 6.74-88.98) of HD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Voltan, Filho, Leite, De Paula, Santana, Silva, Barreto, Da Silva, Conde, Salgado and Frade.)

Objective: To estimate the prevalence, incidence, and prognosis of back pain in children and adolescents., Design: Prospective cohort study., Methods: We followed children and adolescents between the ages of 8 and 18 years with and without back pain over 12 months (3, 6, and 12 months) from public and private schools. At baseline, parents (or guardians) answered questionnaires including sociodemographic characteristics and perception of sleep quality of their children and adolescents. Children and adolescents answered questionnaires including sociodemographic characteristics, presence of back pain, pain intensity, quality of life, and psychosomatic symptoms. At follow-up, children and adolescents answered questions about the presence of back pain., Results: Six hundred fifteen children and adolescents were included, 163 of whom had back pain and 452 of whom had no back pain at baseline. The mean age of participants was 11.6 years (SD = 2.5), and the majority were female (n = 362; 59%). The 1-month prevalence of back pain was 26% (95% confidence interval: 23%-30%). The incidence rate of back pain was 35% (31%-40%) over 12 months. Of the 163 participants who had back pain at baseline, 83% had recovered by 12 months. Of those who recovered within 6 months, 31% had a recurrence of back pain at the 12-month follow-up., Conclusion: Two to 3 in every 10 children and adolescents reported back pain in the last month. New cases of back pain were reported by 3-4 in every 10 children and adolescents for a period of 12 months. Nearly all children recover within 12 months, but recurrence seems to be common. J Orthop Sports Phys Ther 2022;52(8):554-562. Epub: 19 June 2022. doi:10.2519/jospt.2022.10819 .

Background: Low back pain is a common health condition for all ages. One quarter to a third of children report persistent pain, including low back pain., Clinical Question: The aim of this Clinical Commentary is to provide an overview of evidence-based treatment approaches for children and adolescents with low back pain., Key Results: Physical, psychological, and pharmacological interventions are effective in reducing pain intensity and disability. Interdisciplinary and patient- and family-centered treatment approaches are the gold standard for persistent pain in children and adolescents. Communication between health professionals, children, and parents is a key part of a therapeutic alliance. The use of holistic and complementary therapies is not supported by compelling evidence., Clinical Application: Physical interventions can be delivered alone or as a component of other interventions. The interventions are delivered over 8 to 12 weeks. Psychological therapies are mostly delivered as a component of a multidisciplinary treatment program: cognitive behavioral therapy is most often used, and interventions usually run from 4 to 10 weeks. Pharmacological interventions should be delivered in combination with physical and psychological interventions. Tailor family-centered interventions to personal aspects, such as age, gender, and family structure. When communicating with children and adolescents, use simple language that is clear and direct. Aim to support trust between health professionals and parents to facilitate family decision making. J Orthop Sports Phys Ther 2022;52(7):419-424. Epub: 18 May 2022. doi:10.2519/jospt.2022.10768 .

Background: Psychosomatic symptoms seem to influence both the onset and development of pain. There is lack of Brazilian-Portuguese questionnaires that measure psychosomatic symptoms in children and adolescents., Objective: To translate and cross-culturally adapt the Psychosomatic Questionnaire for Children and Adolescents into Brazilian-Portuguese and English and test the measurement properties of the Brazilian-Portuguese version., Methods: The translation and cross-cultural adaptation (from Dutch to Brazilian-Portuguese and English) followed six steps. Interviews were conducted in 33 Brazilian children and adolescents. We also recruited 107 children and adolescents with musculoskeletal pain from schools to test the measurement properties of the Brazilian-Portuguese version. The questionnaire was completed twice with a 7-day interval. Ceiling and floor effects, missing data, internal consistency, reliability, measurement error and construct validity were assessed., Results: We recruited 140 children and adolescents from public and private schools. During the cross-cultural adaptation process, no major difficulty answering and understanding the questionnaire were reported by children and adolescents. The questionnaire did not show ceiling or floor effects and had minimal missing data (0.37%). Internal consistency by the Cronbach's Alpha was 0.69. Test-retest reliability by the Intraclass Correlation Coefficient was 0.75 (95% CI: 0.64, 0.84). The smallest detectable change was 6.5 points out of 18 points. We observed a moderate correlation of 0.54 (p<0.01) with the Spence Children's Anxiety Scale, consistent with our a-priori hypothesis., Conclusion: The Brazilian-Portuguese version of the Psychosomatic Questionnaire for Children and Adolescents has acceptable measurement properties and is a good option for assessing psychosomatic symptoms in clinical practice and research., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2022 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Regarding the leprosy transmission through the upper airways, overcrowded locations such as prisons can become a risk to get sick. Like the leprosy hidden endemic demonstrated in male prison population, being interesting to assess the leprosy scene also among confined women., Methods: A prospective descriptive study conducted at Female Penitentiary, Brazil. Leprosy Suspicion Questionnaire (LSQ) were applied to the participants, and submitted to specialized dermatoneurological exam, peripheral nerve ultrasonography, and anti-PGL-I serology., Findings: 404 female inmates were evaluated, 14 new cases were diagnosed (LG-leprosy group), a new case detection rate (NCDR) of 3.4%, 13 multibacillary, while another 390 constituted the Non-Leprosy group (NLG). Leprosy cases were followed up during multidrug therapy with clinical improvement. The confinement time median was 31 months in LG, similar to NLG, less than the time of leprosy incubation. Regarding LSQ, the neurological symptoms reached the highest x2 values as Q1-numbness (5.6), Q3-anesthetizes areas in the skin (7.5), Q5-Stinging sensation (5.8), and Q7-pain in the nerves (34.7), while Q4-spots on the skin was 4.94. When more than one question were marked in the LSQ means a 12.8-fold higher to have the disease than a subject who marked only one or none. The high 34% rate of anti-PGL-I seropositivity in the penitentiary, higher levels in LG than NLG. Three additional leprosy cases each were diagnosed on the second (n = 66) and third (n = 14) reevaluations 18 and 36 months after the initial one. Semmes-Weinstein monofilaments demonstrated lower limbs (32.2%) more affected than the upper limbs (25%) with improvement during the follow-up., Interpretation: The NCDR in this population showed an hidden endemic of leprosy as well as the efficacy of a search action on the part of a specialized team with the aid of the LSQ and anti-PGL-I serology as an auxiliary tracking tools., Competing Interests: The authors have declared that no competing interests exist.

Acute injuries, such as surgical and traumatic, heal normally in an organized and rapid manner. Studies point to the healing activity of hyaluronic acid in all phases of healing. The aim was to evaluate the effectiveness of hyaluronic acid in skin abrasions on the dorsum of rats to compare to usual products on the market. Seventy-two Wistar rats were subjected to excoriation of approximately 2.0 cm 2 on the back by dermabrasion. According to the treatment, 3 groups were established: saline, chlorhexidine digluconate and 0.2% hyaluronic acid for 14 days. Animals were photographed on the 2 nd , 7 th , 10 th and 14 th postinjury days, and the index of healing of the abrasions was calculated. Biochemically, myeloperoxidase measurements of skin biopsies in addition to histological studies to assess the crust and epidermal layers were performed. The group treated with hyaluronic acid showed better re-epithelialization from the other groups (p < 0.05) on the 7 th and 10 th days. For the thickness of the crust, the hyaluronic acid group presented thinner crust than other groups on the 10 th and 14 th days (p < 0.05), but in the epidermis, no difference was observed between the groups studied. All groups showed an increase in myeloperoxidase enzyme on the 2 nd day, but a decreasing on the 7 th day. On the 10 th day, there was a difference in the hyaluronic acid group compared to the other groups (p < 0.05). The application of 0.2% hyaluronic acid significantly accelerated the re-epithelialization of skin abrasions compared to saline and chlorhexidine digluconate., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Skin wounds have been a public health concern of high frequency, in addition to requiring intensive and expensive care. The natural rubber latex (NRL) from Hancornia speciosa Gomes has been used to treat many problems in traditional medicine and also present healing properties, antifungal and anti-inflammatory activity and antinociceptive effects. The purpose of this study was to characterize the new biomembrane from the NRL of H. speciosa (HS) by Fourier transform infrared (FTIR) and mechanical strength test and to investigate its biological properties by the cytotoxicity assay and in vivo healing activity. The results showed that the HS biomembrane exhibited characteristic bands of the main component cis-1,4-polyisoprene. Besides, its Young modulus was close to human skin with adhesive-compatible mechanical characteristics. The cytotoxicity assays revealed that the HS biomembrane was not toxic to fibroblast cells neither using agar diffusion test nor MTT assay. Furthermore, the HS biomembrane stimulated the inflammatory cells and the angiogenesis, increased significantly the collagenesis and improved the quality of heal until the remodeling phase induced by implants in mice. Thus, this biomembrane has proven to be a safe and biocompatible biomaterial with healing potential, becoming an effective and low-cost alternative for the treatment of skin wounds., (© 2020 Wiley Periodicals LLC.)

Background: This study evaluates implementation strategies for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzes immunoepidemiological aspects and follow-up of individuals living in a presumptively nonendemic area in Brazil., Methodology/principal Findings: Quasi-experimental study based on LSQ throughout Jardinópolis town by community health agents, theoretical-practical trainings for primary care teams, dermatoneurological examination, anti-PGL-I serology, RLEP-PCR, and spatial epidemiology. A Leprosy Group (LG, n = 64) and Non-Leprosy Group (NLG, n = 415) were established. Overall, 3,241 LSQs were distributed; 1,054 (32.5%) LSQ were positive for signs/symptoms (LSQ+). Among LSQ+ respondents, Q2-Tingling (pricking)? (11.8%); Q4-Spots on the skin? (11.7%); Q7-Pain in the nerves? (11.6%); Q1-Numbness in your hands and/or feet? (10.7%) and Q8-Swelling of hands and feet? (8.5%) were most frequently reported symptoms. We evaluated 479 (14.8%) individuals and diagnosed 64 new cases, a general new case detection rate (NCDR) of 13.4%; 60 were among 300 LSQ+ (NCDR-20%), while 4 were among 179 LSQ negative (NCDR-2.23%). In LG, Q7(65%), Q2(60%), Q1(45%), Q4(40%) and Q8(25%) were most frequent. All 2x2 crossings of these 5 questions showed a relative risk for leprosy ranging from 3 to 5.8 compared with NLG. All patients were multibacillary and presented hypochromatic macules with loss of sensation. LG anti-PGL-I titers were higher than NLG, while 8.9% were positive for RLEP-PCR. The leprosy cases and anti-PGL-I spatial mappings demonstrated the disease spread across the town., Conclusions/significance: Implementation actions, primarily LSQ administration focused on neurological symptoms, indicate hidden endemic leprosy in a nonendemic Brazilian state., Competing Interests: The authors have declared that no competing interests exist.

Alternative models to replace animals in experimental studies remain a challenge in testing the effectiveness of dermatologic and cosmetic drugs. We proposed a model of human organotypic skin explant culture (hOSEC) to assess the profile of cutaneous drug skin distribution, adopting dacarbazine as a model, and respective new methodologies for dermatokinetic analysis. The viability tests were evaluated in primary keratinocytes and fibroblasts, and skin by MTT and TTC assays, respectively. Then, dacarbazine was applied to the culture medium, and the hOSEC method was applied to verify the dynamics of skin distribution of dacarbazine and determine its dermatokinetic profile. The results of cell and tissue viability showed that both were considered viable. The dermatokinetic results indicated that dacarbazine can be absorbed through the skin, reaching a concentration of 36.36 µg/mL (18,18%) of the initial dose (200 µg/mL) after 12 h in culture. Histological data showed that the skin maintained its structure throughout the tested time that the hOSEC method was applied. No apoptotic cells were observed in the epidermal and dermal layers. No visible changes in the dermo-epidermal junction and no inflammatory processes with the recruitment of defense cells were observed. Hence, these findings suggest that the hOSEC concept as an alternative ex vivo model for assessing the dynamics of skin distribution of drugs, such as dacarbazine, and determining their respective dermatokinetic profiles., (Copyright © 2021. Published by Elsevier B.V.)

Background: This study evaluates an active search strategy for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzing the clinical, immunoepidemiological and follow-up aspects for individuals living in a prison population., Methods: A cross-sectional study based on a questionnaire posing 14 questions about leprosy symptoms and signs that was distributed to 1,400 prisoners. This was followed by dermatoneurological examination, anti-PGL-I serology and RLEP-PCR. Those without leprosy were placed in the Non-leprosy Group (NLG, n = 1,216) and those diagnosed with clinical symptoms of leprosy were placed in the Leprosy Group (LG, n = 34)., Findings: In total, 896 LSQ were returned (64%), and 187 (20.9%) of the responses were deemed as positive for signs/symptoms, answering 2.7 questions on average. Clinically, 1,250 (89.3%) of the prisoners were evaluated resulting in the diagnosis of 34 new cases (LG), based on well-accepted clinical signs and symptoms, a new case detection rate of 2.7% within this population, while the NLG were comprised of 1,216 individuals. The confinement time medians were 39 months in the LG while it was 36 months in the NLG (p>0.05). The 31 leprosy cases who responded to the questionnaire (LSQ+) had an average of 1.5 responses. The symptoms "anesthetized skin area" and "pain in nerves" were most commonly mentioned in the LG while "tingling, numbness in the hands/feet", "sensation of pricks and needles", "pain in nerves" and "spots on the skin" responses were found in more than 30% of questionnaires in the NLG. Clinically, 88.2% had dysesthetic macular skin lesions and 97.1% presented some peripheral nerve impairment, 71.9% with some degree of disability. All cases were multibacillary, confirming a late diagnosis. Anti-PGL-I results in the LG were higher than in the NLG (p<0.0001), while the RLEP-PCR was positive in 11.8% of the patients., Interpretation: Our findings within the penitentiary demonstrated a hidden prevalence of leprosy, although the individuals diagnosed were likely infected while living in their former communities and not as a result of exposure in the prison. The LSQ proved to be an important screening tool to help identify leprosy cases in prisons., Competing Interests: The authors have declared that no competing interests exist.

Background: Dermabrasion is related with mechanical and surgical traumas on the skin; usually topical antiseptics and/or saline have been used for healing. Natural products for wound healing can also be used for abrasions, such as latex from Hevea brasiliensis., Objective: This study aimed to evaluate the in vitro viability and migratory/proliferative effects of latex serum from H. brasiliensis and to compare with a commercially available standard antiseptic solution and saline in experimental dermabrasion on rats., Methods: For in vitro evaluation, MTT and scratch assays were used. In vivo testing was performed in 72 rats submitted to dermabrasion, treated with saline, antiseptic, or latex serum. This study evaluated re-epithelialization, neutrophilic infiltration, and the quantification of crust and epidermis., Results: Latex showed viability at 1% and 0.1% concentrations and migratory/proliferative activity at 0.01% concentrations. The re-epithelialization was highest in latex group on 7th day. The latex group displayed lower thickness of crusts and greater extent of epidermal layers. The latex and antiseptic groups showed increases of myeloperoxidase levels on the 2nd day and showed important reductions from the 7th day., Study Limitations: Acute superficial wound model in rats and non-use of gel-cream (medium) without latex., Conclusion: In conclusion, non-toxic latex stimulated migration/proliferation of keratinocytes in vitro and significantly accelerated wound healing in animal excoriation models compared to chlorhexidine or saline., (Copyright © 2020 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Wound healing studies are intricate, mainly because of the multifaceted nature of the wound environment and the complexity of the healing process, which integrates a variety of cells and repair phases, including inflammation, proliferation, reepithelialization and remodelling. There are a variety of possible preclinical models, such as in mice, rabbits and pigs, which can be used to mimic acute or impaired for example, diabetic and nutrition-related wounds. These can be induced by many different techniques, with excision or incision being the most common. After determining a suitable model for a study, investigators need to select appropriate and reproducible methods that will allow the monitoring of the wound progression over time. The assessment can be performed by non-invasive protocols such as wound tracing, photographic documentation (including image analysis), biophysical techniques and/or by invasive protocols that will require wound biopsies. In this article, we provide an overview of some of the most often needed and used: (a) preclinical/animal models including incisional, excisional, burn and impaired wounds; (b) methods to evaluate the healing progression such as wound healing rate, wound analysis by image, biophysical assessment, histopathological, immunological and biochemical assays. The aim is to help researchers during the design and execution of their wound healing studies., (© 2020 Company of the International Journal of Experimental Pathology (CIJEP).)

The considerable role of pristine bacterial cellulose membranes (BC) as ideal dressings have been widely demonstrated to treat wounds and burns. Nevertheless, drawbacks regarding antimicrobial spectrum and frequent dressing replacement are still present. Based on this, the present work proposes an innovative dressing by incorporating a technological self-microemulsifying formulation (SMEF) encapsulating propolis (BC/PP). BC/PP was fully chemically and biologically characterized employing in vitro and in vivo models. Antimicrobial studies demonstrated BC/PP high efficiency against both gran-negative and gran-positive bacteria. Release studies evidenced propolis markers sustained release for up to 7 days. In vivo wound healing activity was assessed by wound healing rate, anti-inflammatory and tissue formation events and the results evidenced the pro-inflammatory activity of BC/PP, which could promote improved healing results. To conclude, BC/PP presented an outstanding antibacterial activity in vitro with weekly replacement and promotion of healing, offering, for the first time, a broad-spectrum biomembrane potential to treat infected wounds., (Copyright © 2019. Published by Elsevier B.V.)

The use of mesenchymal stem cells (MSCs) in tissue engineering has been extensively investigated. The greater the proliferation of this cellular group, the greater the regenerative and healing capacity of the tissue to which they belong. In this context, photobiomodulation (PBM) is an efficient technique in proliferation of distinct cell types. However, its parameters and mode of action are still unclear and require further investigation. This study aimed to evaluate the PBM action with different energies in MSCs of adipose tissue (hASCs). We used hASCs, seeded in 24-well plates, with 3 × 10 4 cells per well, in culture media. We used a total of four experimental groups, one with hASCs and simulated PBM and three other groups, which received PBM irradiation at 24, 48, and 72 h, with a 660-nm laser and power of 40 mW and energy of 0.56, 1.96, and 5.04 J. We performed analyses of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidefor) and trypan blue to evaluate cell proliferation and viability, 1 h after PBM irradiation. Software Graph PadPrism 7.0 was used. Intergroup comparisons were performed with ANOVA two-way and we used the Tukey post hoc test. Mitochondrial activity evaluated by MTT revealed the statistical difference in the first 24 h for group with more high energy when compared to control group; and in the 72 h for two irradiated groups when compared to the control group. The trypan blue test showed significant differences at the end of the experiment for two irradiated groups LG1 (4.52 × 10 4  ± 0.2) and LG2 (4.85 × 104 ± 0.8), when compared to the control group (1.87 × 10 4  ± 0.7). Both tests failed to be statistically different at the end of the experiment for groups LG1 and LG2 and observed a reduction in cellular mitochondrial growth and activity for group LG3. We conclude that PBM with energy close to 0.56 and 1.96 J promote proliferation of hASCs, and higher energy, such as 5.04 J, can be harmful.

Natural rubber latex (NRL) is a natural polymer which has arisen large interest in the biomedical field, mostly, due to its ability to facilitate angiogenesis and therefore, tissue repair. Moxifloxacin (MXF) is a broad-spectrum antibiotic orally administrated. Considering the biological properties of the NRL and its ability to deliver a wide range of compounds, the present study aimed to develop a novel device for infected chronic wound treatment. MXF-loaded NRL was obtained by a casting method. The results demonstrated that the incorporation of MXF in NRL did not promote any molecular interaction, preserving the integrity of the compounds. The mechanical properties of the biomaterial did not show any significant change, indicating enough elasticity for dermal application. The microbiological assays confirmed the ability of the polymer to deliver the drug without influencing its pharmacological properties. Moreover, it has expressed activity against major bacterial strains presented in wound infections. Finally, the biomaterial shown biocompatibility from the in vitro study. Thus, the present work has shown that MXF-loaded NRL membrane is a promising biomaterial to infected wound treatment.

Objectives: Show that hidden endemic leprosy exists in a municipality of inner São Paulo state (Brazil) with active surveillance actions based on clinical and immunological evaluations., Methods: The study sample was composed by people randomly selected by a dermatologist during medical care in the public emergency department and by active surveillance carried out during two days at a mobile clinic. All subjects received a dermato-neurological examination and blood sampling to determine anti-PGL-I antibody titers by enzyme-linked immunosorbent assay (ELISA)., Results: From July to December 2015, 24 new cases of leprosy were diagnosed; all were classified as multibacillary (MB) leprosy, one with severe Lucio's phenomenon. Seventeen (75%) were found with grade-1 or 2 disability at the moment of diagnosis. Anti-PGL-I titer was positive in 31/133 (23.3%) individuals, only 6/24 (25%) were positive in newly diagnosed leprosy cases., Conclusions: During the last ten years before this study, the average new case detection rate (NCDR) in this town was 2.62/100,000 population. After our work, the NCDR was raised to 42.8/100,000. These results indicate a very high number of hidden leprosy cases in this supposedly low endemic area of Brazil.

Lipoxin A4 (LXA4) is involved in the resolution of inflammation and wound healing; however, it is extremely unstable. Thus, to preserve its biological activities and confer stability, we encapsulated LXA4 in poly-lactic-co-glycolic acid (PLGA) microparticles (LXA4-MS) and assessed its application in treating dorsal rat skin lesions. Ulcers were sealed with fibrin adhesive and treated with either LXA4-MS, unloaded microparticles (Un-MS), soluble LXA4, or PBS/glue (vehicle). All groups were compared at 0, 2, 7, and 14 days post-lesions. Our results revealed that LXA4-MS accelerated wound healing from day 7 and reduced initial ulcer diameters by 80%. Soluble LXA4, Un-MS, or PBS closed wounds by 60%, 45%, and 39%, respectively. LXA4-MS reduced IL-1β and TNF-α, but increased TGF-β, collagen deposition, and the number of blood vessels. Compared to other treatments, LXA4-MS reduced inflammatory cell numbers, myeloperoxidase (MPO) concentration, and metalloproteinase-8 (MMP8) mRNA in scar tissue, indicating decreased neutrophil chemotaxis. In addition, LXA4-MS treatment increased macrophages and IL-4, suggesting a positive impact on wound healing. Finally, we demonstrated that WRW4, a selective LXA4 receptor (ALX) antagonist, reversed healing by 50%, indicating that LXA4 must interact with ALX to induce wound healing. Our results show that LXA4-MS could be used as a pharmaceutical formulation for the treatment of skin ulcers.

Context: The quantification of total collagen is of major importance in a wide range of research areas, including the study of cutaneous wound healing and new drugs trials., Objective: The total collagen content in skin biopsies was compared by biochemical hydroxyproline assay and by two computer-aided histomorphometric analyses of histological sections., Materials and Methods: Two methods were used to evaluate collagen formation: the hydroxyproline assay, as the gold standard and histomorphometric image analysis of the filled areas by corresponding stained collagen fibres, using picrosirius and Gomori's trichrome staining. The image analyses were determined by digital densitometry recognition using computer-aided ImageJ software. One-way ANOVA, simple linear regression and ANCOVA were applied for the statistical analysis and correlation., Results: In a simple linear regression analysis carried out on the 14th day period after the induction of skin injury, three techniques, picrosirius red (F = 33.57, p = 0.00), Gomori's trichrome (F = 81.61, p = 0.00) and hydroxyproline content (F = 16.85, p = 0.00) were able to detect collagen production. After scale adjustment, there were no significant differences among either the slopes (F = 1.17, p = 0.32) or the intercepts (F = 0.69, p = 0.51) of the estimated regression lines. It seems that a highly significant correlation exists between the histomorphometrical analysis and hydroxyproline assay., Discussion and Conclusion: The morphometric analysis proved to be adequate and can be used as a simple, rapid, low-cost technology for evaluating total collagen in cutaneous wound specimens, compared with the gold standard hydroxyproline assay.

This study aimed to compare the phototherapy effects on wound healing in rats submitted to normal and high-fat diets. Thirty-six rats received normal lipidic diet (NL) and 36 high lipidic (HL) diet for 45 days. The nutritional status was measured by body mass, blood glucose, total cholesterol, and triglycerides levels. Four experimental groups were performed according light (L) therapy applied "on" or "off" (660 nm, 100 mW, 70 J/cm(2), 2 J) on 1.5-mm-punched dorsum skin wounds as NLL+, NLL-, HLL+, and HLL-. The wound healing rate (WHR) and oxidative stress markers were analyzed on 2nd, 7th, and 14th days. Despite no difference among body mass, the HL rats presented higher blood glucose, total cholesterol, and triglycerides levels than NL rats. Respectively, on the 2nd and 14th days, the HLL+ group presented the highest WHRs (0.38 ± 0.16/0.97 ± 0.02) among all groups, while the HLL- (-0.002 ± 0.12/0.81 ± 12.1) the lowest WHRs. Hydroxyproline level was lower in HLL- (6.41 ± 1.09 μg/mg) than HLL+ (7.71 ± 0.61 μg/mg) and also NLL+ (9.33 ± 0.84 μg/mg). HLL+ presented oxidative stress markers similar to normal control group (NLL-) during follow up and highest antioxidant defense on 7th day. The results showed phototherapy accelerated the cutaneous wound healing by modulating oxidative stress in rats with metabolic disorders under a high-fat diet.

The purpose of this study was to evaluate the efficacy of chitosan-alginate membrane to accelerate wound healing in experimental cutaneous wounds. Two wounds were performed in Wistar rats by punching (1.5 cm diameter), treated with membranes moistened with saline solution (CAM group) or with saline only (SL group). After 2, 7, 14, and 21 days of surgery, five rats of each group were euthanized and reepithelialization was evaluated. The wounds/scars were harvested for histological, flow cytometry, neutrophil infiltrate, and hydroxyproline analysis. CAM group presented higher inflammatory cells recruitment as compared to SL group on 2(nd) day. On the 7(th) day, CAM group showed higher CD11b(+) level and lower of neutrophils than SL group. The CAM group presented higher CD4(+) cells influx than SL group on 2(nd) day, but it decreased during the follow up and became lower on 14(th) and 21(st) days. Higher fibroplasia was noticed on days 7 and 14 as well as higher collagenesis on 21(st) in the CAM group in comparison to SL group. CAM group showed faster reepithelialization on 7(th) day than SL group, although similar in other days. In conclusion, chitosan-alginate membrane modulated the inflammatory phase, stimulated fibroplasia and collagenesis, accelerating wound healing process in rats., (© 2014 Wiley Periodicals, Inc.)

Background: Currently, the cosmetic industry is overwhelmed in keeping up with the safety assessment of the increasing number of new products entering the market. To meet such demand, research centers have explored alternative methods to animal testing and also the large number of volunteers necessary for preclinical and clinical tests., Objectives: This work describes the human skin ex-vivo model (hOSEC: Human Organotypic Skin Explant Culture) as an alternative to test the effectiveness of cosmetics and demonstrate its viability through cutaneous keratinocytes' proliferative capacity up to 75 days in culture., Methods: The skin explants obtained from surgeries were cultured in CO2-humid incubator. After 1, 7, 30 and 75 days in culture, skin fragments were harvested for analysis with histomorphological exam (HE staining) on all days of follow-up and immunohistochemistry for Ck5/6, Ck10 and Ki-67 only on the 75th day., Results: On the 7th day, the epidermis was perfect in the dermoepidermal junction, showing the viability of the model. On the 30th day, the epidermis was thicker, with fewer layers on the stratum corneum, although the cutaneous structure was unaltered. On the 75th day, the skin became thinner but the dermoepidermal junctions were preserved and epidermal proliferation was maintained. After the 75th day on culture, the skin was similar to normal skin, expressing keratinocytes with Ck5/6 on supra-basal layers; Ck10 on differentiated layers; and viability could be assessed by the positivity of basal cells by Ki-67., Conclusion: The hOSEC model seems a good alternative to animal testing; it can be used as a preclinical test analogous to clinical human skin test with similar effectiveness and viability proven by immunohistological analyses.

Hyaluronidases are enzymes that degrade hyaluronan an important constituent of the extracellular matrix. They have been used as a spreading agent, improving the absorption of drugs and facilitating the subcutaneous infusion of fluids. Here, we investigated the influence of bovine testes hyaluronidase (HYAL) during cutaneous wound healing in in vitro and in vivo assays. We demonstrated in the wound scratch assay that HYAL increased the migration and proliferation of fibroblasts in vitro at low concentration, e.g. 0.1 U HYAL enhanced the cell number by 20%. HYAL presented faster and higher reepithelialization in in vivo full-thickness excisional wounds generated on adult Wistar rats back skin already in the early phase at 2nd day post operatory compared to vehicle-control group. Wound closured area observed in the 16 U and 32 U HYAL treated rats reached 38% and 46% compared to 19% in the controls, respectively. Histological and biochemical analyses supported the clinical observations and showed that HYAL treated wounds exhibited increased granulation tissue, diminished edema formation and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines, growth factor and eicosanoids mediators. Moreover, HYAL increased gene expression of peroxisome proliferator-activated receptors (PPAR) γ and PPAR β/δ, the collagen content in the early stages of healing processes as well as angiogenesis. Altogether these data revealed that HYAL accelerates wound healing processes and might be beneficial for treating wound disorders.

Background: Various studies have shown that phototherapy promotes the healing of cutaneous wounds., Objective: To investigate the effect of phototherapy on healing of cutaneous wounds in nourished and undernourished rats., Methods: Forty rats, 20 nourished plus 20 others rendered marasmus with undernourishment, were assigned to four equal groups: nourished sham, nourished Light Emitting Diode treated, undernourished sham and undernourished Light Emitting Diode treated. In the two treated groups, two 8-mm punch wounds made on the dorsum of each rat were irradiated three times per week with 3 J/cm2 sq cm of combined 660 and 890 nm light; wounds in the other groups were not irradiated. Wounds were evaluated with digital photography and image analysis, either on day 7 or day 14, with biopsies obtained on day 14 for histological studies., Results: Undernourishment retarded the mean healing rate of the undernourished sham wounds (p < 0.01), but not the undernourished Light emission diode treated wounds, which healed significantly faster (p < 0.001) and as fast as the two nourished groups. Histological analysis showed a smaller percentage of collagen in the undernourished sham group compared with the three other groups, thus confirming our photographic image analysis data., Conclusion: Phototherapy reverses the adverse healing effects of undernourishment. Similar beneficial effects may be achieved in patients with poor nutritional status.

Introduction: Seeds of Aesculus hippocastanum L. are used in European phytotherapy to treat inflammatory and vascular problems, and also to help in the regulation of the microcirculation. Thus, the quality control of herbal medicines using this species is important., Objective: To develop and to optimise a capillary zone electrophoresis method to determine total β-escin in different extracts of A. hippocastanum L., Methods: The optimal condition found through chemometric approach was: 25 mmol/L of bicarbonate-carbonate buffer, pH 10.3; +20 kV of voltage; 20°C of cartridge temperature; direct ultraviolet detection at 226 nm; 13 mbar injection for 5 s and analysis time within 6 min., Results: Repeatability, coefficient of variation (CV; %) = 3.19, 3.07 and 1.89 (n = 12), and intermediate precision, CV (%) = 3.05, 3.53 and 2.99 (n = 24) for dry, hydroalcoholic and hydroglycolic extracts, respectively were achieved. The accuracy was evaluated through recovery tests in concentration levels of 100, 150 and 200 g/L, ranging from 98.17 to 104.68%. The proposed method exhibited linearity (r = 0.9983) in the concentration range from 101.4 to 907.2 g/L and limits of detection and quantification equal to 11.63 and 38.76 g/L respectively., Conclusion: A fast and reliable methodology for determination of total β-escin was successfully validated and applied on extracts of A. hippocastanum L. demonstrating its usefulness to quality control of medicines containing this plant species., (Copyright © 2013 John Wiley & Sons, Ltd.)

Ethnopharmacological Relevance: Psidium cattleianum Sabine is extensively used in Brazilian traditional medicine to treat several diseases including painful disorders. Aim of the study to investigate the toxicity and the possible analgesic activities of the hydroalcoholic extract from the leaves of Psidium cattleianum Sabine (ELPCS), to support its use in folk medicine. To screen the major phytochemical constituents of this extract and evaluate their antioxidant activity., Materials and Methods: ELPCS was assessed for its antioxidant activity using the DPPH model. Its analgesic activity was examined using mouse models of acetic acid-induced writhing and hot plate paw licking models. The major phytochemical constituents of the extract were screened; their toxicity on LLC-MK2 mammalian cells was evaluated., Results: ELPCS exhibited significant peripheral analgesic activity at doses of 60, 80, 100, 200 and 400mg/kg in mice, but it did not display central analgesic activity and not was toxic to LLC-MK2 cell (LD50>400 µg/mL). The extract exhibited free radical scavenging activity as evidenced by IC50 values (15.9 µg/mL) obtained by the DPPH method. Phytochemical screening detected flavonoids, saponins, cardiac glycosides, anthraquinones, and tannins., Conclusions: The results of the experimental studies proved the analgesic activity of ELPCS and supported the traditional use of this plant., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Morus nigra L. is a plant employed as a substitute for the conventional hormonal replacement therapy. This work analyzes the estrogenic effect of M. nigra on the reproductive system and embryonic development of Wistar rats. Female rats were orally treated with M. nigra hydroalcoholic extract (MnHE) at the dose levels of 25, 50, 75, 350 and 700 mg/kg of body weight over 15 days, and continued through mating until the 14th day of gestation. Vaginal smears were performed daily and the body weight of the females was recorded at 5 days intervals. On day 15 of gestation, the females were killed and their kidneys, liver, spleen and ovaries were removed and weighed. The number of implants, resorptions, and live and dead fetuses were evaluated. Histological sections of ovaries, measurement of the height of the uterine epithelium and vaginal smears were performed to assess the estrogenic activity. The results showed that the administration of MnHE did not significantly alter the analyzed variables. Therefore, considering the experimental model used in this study, the data obtained indicate that M. nigra did not exhibit any estrogenic activity nor did exert a toxic effect on the female reproductive system and on the embryonic development of rats., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In the present study the phenolic (Folin-Dennis) and flavonoid (colorimetric assay) constituents and the antioxidant activity of Pterodon emarginatus seeds were investigated in several samples prepared with different extraction procedures: essential oil (EO) using a Clevenger-type apparatus; hexanic (HF), ethyl acetate (EAF), buthanolic (BF) and methanolic (MF) fractions using Soxhlet extraction, and extracts (1 g/extract) obtained from different methods: reflux 80 degrees C/30 min, ultrasound/30 min, static maceration/48 h and heating plate 100 degrees C/45 min. These extracts were prepared using water or ethanol/water at 30:70 v/v, 50:50 v/v or 70:30 v/v. Antioxidant activity [2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH)] was tested only in the fractions obtained from Soxhlet extraction. The extract obtained from reflux using ethanol/water (70:30, v/v) showed the highest phenolic constituents level. The EAF, BF and MF showed DPPH scavenging activities with IC(50)=163.22, 18.89 and 10.15 microg/ml, respectively.

Many plant substances are known for their interference with the reproductive system. Mikania glomerata is a plant popularly used to treat respiratory diseases and is reported to have flavonoids and coumarin, which have been shown to have antifertility activity in male dogs and female rats, respectively. This work analyzes the effect of a high dose of M. glomerata extract administered during the spermatogenic cycle of rats. Adult Wistar rats were treated with 1 mL of a M. glomerata extract at a dose level of 3.3 g/kg of body weight for 52 days. Body and organ weights, sperm production, circulating testosterone level and food consumption were evaluated. The results showed that the administration of the M. glomerata extract during the rat spermatogenic cycle did not significantly alter the body and organ weights nor did it interfere with gamete production, serum testosterone level or food intake.