Bioscientia Medicina - Journal of Biomedicine and Translational Research
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Dose- and Time-Dependent Efficacy of Topical Hydroquinone in Establishing a C57BL/6 Mouse Model of Vitiligo
Background: Vitiligo is a complex autoimmune depigmenting disorder driven by melanocyte-specific CD8+ T cells, oxidative stress, and genetic susceptibility. The lack of standardized, accessible animal models that recapitulate these pathways hinders therapeutic development. This study aimed to systematically optimize and validate a chemically-induced vitiligo model in C57BL/6 mice.
Methods: Eighty (80) male C57BL/6 mice were randomized into ten groups (n=8/group). Experimental groups received once-daily topical applications of hydroquinone (HQ) at 2.5%, 5%, or 10%, or monobenzone (MBZ) at 40% for 8 or 16 days. Vehicle-treated mice served as controls. Efficacy was assessed via quantitative histopathology (Masson-Fontana staining for melanin area), biomolecular assays for oxidative stress (Malondialdehyde [MDA] and Superoxide Dismutase [SOD]), and RT-qPCR for melanogenesis-related (Tyr) and inflammation-related (Tnf) gene expression.
Results: A clear dose- and time-dependent depigmentation was observed. The 10% HQ 16-day protocol was maximally effective, inducing a profound reduction in epidermal melanin area (0.06 ± 0.02) compared to 16-day controls (0.40 ± 0.04; p < 0.001). This histopathological finding was significantly correlated with severe cutaneous oxidative stress, evidenced by a 3.75-fold increase in MDA (p < 0.001) and a 50% reduction in SOD activity (p < 0.001) versus controls. Furthermore, this regimen caused a potent suppression of Tyr expression (0.15-fold change; p < 0.001) and a significant upregulation of the pro-inflammatory cytokine Tnf (3.8-fold change; p < 0.001).
Conclusion: The 16-day topical application of 10% hydroquinone is a reliable, rapid, and highly reproducible protocol for inducing vitiligo-like depigmentation in C57BL/6 mice. This model successfully recapitulates key pathophysiological pillars of human vitiligo, including melanocytotoxicity, profound oxidative stress, and a pro-inflammatory cutaneous environment, establishing it as a valuable platform for preclinical therapeutic screening
The Clinical Spectrum and Management Patterns of Orbital Meningioma: A 6-Year Single-Institution Case Series from Indonesia
Background: Orbital meningiomas (OMs) are rare, complex tumors whose clinical course and management are debated. Data from Southeast Asian populations, particularly Indonesia, is scarce. This study aims to define the clinical spectrum, radiological features, and management trends of OMs at a single Indonesian tertiary referral center, with a focus on hormonal factors in a predominantly female cohort.
Methods: A retrospective, descriptive case series was conducted on all patients diagnosed with orbital meningioma at Dr. M. Djamil General Hospital, Padang, Indonesia, from January 2018 to December 2023. Data on demographics, detailed clinical presentation (visual acuity, proptosis, extraocular movement), radiological findings (location, size, hyperostosis), and hormonal risk factors were collected. Management strategies, histopathological results (WHO grade), and follow-up outcomes were analyzed.
Results: Twenty patients were included, with a significant female predominance (n=16, 80%; F:M ratio 4:1). The median age at diagnosis was 47 years (range 28-71). A strong association with hormonal factors was noted; 50% (8/16) of female patients had a history of exogenous hormonal contraceptive use. The most common presenting symptoms were progressive proptosis (n=15, 75%) and visual loss (n=12, 60%). The mean proptosis was 5.5 ± 2.1 mm. The most frequent tumor location was retrobulbar (intraconal) (n=11, 55%), followed by optic nerve sheath (n=5, 25%). A multidisciplinary, conservative-led approach was the primary management strategy, with 75% (n=15) of patients managed with active observation and neurosurgical consultation. Surgical intervention was performed in 25% (n=5) of cases, primarily for severe symptoms or aggressive radiological features. Histopathology (n=5) confirmed WHO Grade I in four cases (80%) and WHO Grade II (atypical) in one case (20%).
Conclusion: Orbital meningiomas in this Indonesian cohort demonstrate a striking female predominance and a strong association with hormonal contraceptive use, suggesting a significant role for hormonal pathways in their pathophysiology. The management paradigm has shifted towards a multidisciplinary, observation-first approach, reserving surgical intervention for cases with documented progression, severe vision loss, or high-grade pathological features
Complete Clinical and Trichoscopic Remission of Refractory Patch Alopecia Areata with a Multi-Modal Microneedling and Vitamin D3 Protocol: A Case Report
Background: Refractory patch alopecia areata (AA) presents a significant therapeutic challenge, as many patients fail first-line treatments. This gap necessitates the exploration of novel, mechanistically-targeted therapeutic strategies.
Case presentation: We present the case of a 44-year-old female with a 2.5 × 3.0 cm patch of AA, refractory to a 3-month compliant trial of topical 0.25% desoximetasone and 5% minoxidil. Baseline diagnostics included histopathology (peribulbar lymphocytic infiltrate), quantitative trichoscopy (yellow dots, black dots, exclamation mark hairs), and laboratory workup, which revealed a serum 25-hydroxyvitamin D [25(OH)D] insufficiency (18.2 ng/mL). A multi-modal protocol was initiated: (1) systemic 5,000 IU/day oral cholecalciferol, (2) 10 sessions of 1.5 mm microneedling at two-week intervals, and (3) immediate post-procedure application of topical 100,000 IU cholecalciferol. Significant regrowth of pigmented terminal hairs was observed by week 12. After 20 weeks (10 sessions), complete clinical regrowth was achieved. Final quantitative trichoscopy confirmed the full resolution of all pathological markers, with a healthy density of terminal hairs. The patient’s systemic 25(OH)D level was corrected to 41.5 ng/mL. The treatment was well-tolerated.
Conclusion: This case report documents a complete remission associated with a multi-modal protocol. The contribution of the systemic vitamin D repletion is a major, unresolvable confounder, making attribution impossible. However, this hypothesis-generating case suggests a combined (systemic, physical, and topical) approach may represent a potential rescue strategy for refractory patch AA, warranting further controlled investigation
Tear Reservoir Thickness and Vector-Resolved Refractive Outcomes in Indonesian Corneal Ectasia: A Scleral Lens Pilot Study
Background: Corneal ectasia is characterized by high-order aberrations and irregular astigmatism, presenting significant optical challenges. Scleral lenses neutralize these irregularities via a post-lens tear reservoir. However, the precise optical contribution of the tear reservoir thickness itself to residual refractive error remains under-characterized, particularly in Southeast Asian populations where aggressive ectasia phenotypes are common. This study aimed to determine if tear reservoir thickness correlates with residual refractive error using vector analysis.
Methods: This retrospective pilot study analyzed 12 eyes of 8 patients with severe corneal ectasia fitted with scleral lenses in Indonesia. Refractive outcomes were converted to Thibos power vectors (M, J0, J45). To account for bilateral eye correlations, linear mixed models (LMM) were employed with Patient ID as a random effect. A theoretical thick-lens model compared predicted versus observed over-refraction.
Results: The cohort (mean age 28 ± 10.2 years) achieved significant visual improvement (LogMAR 0.35 to 0.17; p = 0.005). The mean tear reservoir thickness was 263.33 ± 80.92 μm. LMM analysis revealed no statistically significant correlation between fluid thickness and Spherical Equivalent (M) (beta = -0.001, p = 0.72) or Blur Strength (p = 0.68). The theoretical model indicated that residual error was driven by uncorrected posterior corneal astigmatism rather than fluid depth.
Conclusion: In this Indonesian cohort, optical efficacy was driven by refractive index matching at the corneal interface, not reservoir thickness. Clinical fitting should prioritize physiological clearance over refractive manipulation
Massive Hemoptysis: A Meta-Analysis of Urgent Interventional Approaches
Background: Massive hemoptysis is a life-threatening medical emergency requiring immediate intervention. This meta-analysis evaluated the efficacy and safety of urgent interventional approaches for managing massive hemoptysis.
Methods: A systematic search of electronic databases (PubMed, Embase, Scopus) was conducted from January 2013 to February 2024. Studies comparing different urgent interventional approaches (bronchial artery embolization [BAE], bronchoscopic interventions, surgery) in adults with massive hemoptysis were included. The primary outcome was treatment success (cessation of bleeding). Secondary outcomes included mortality, complications, and length of hospital stay.
Results: Nine studies (n=1145 patients) were included. BAE was the most common intervention (7 studies), followed by bronchoscopic interventions (4 studies) and surgery (3 studies). Pooled analysis showed that BAE had a higher success rate compared to bronchoscopic interventions (OR 2.15, 95% CI 1.32-3.51, p=0.002) and surgery (OR 1.88, 95% CI 1.15-3.08, p=0.01). BAE was associated with a lower mortality rate compared to surgery (OR 0.43, 95% CI 0.21-0.88, p=0.02) but not bronchoscopic interventions (OR 0.78, 95% CI 0.45-1.35, p=0.37). Complication rates were similar across all interventions.
Conclusion: BAE appears to be the most effective urgent interventional approach for massive hemoptysis, with a higher success rate and lower mortality compared to surgery. Bronchoscopic interventions may be considered in selected cases. Further research is needed to compare different BAE techniques and optimize patient selection
Navigating Diagnosis and Treatment of Perianal Condyloma Acuminata in a Bisexual Man: Clinical and Histopathological Insights
Background: Condyloma acuminata (CA), caused by Human Papillomavirus (HPV), commonly affects the anogenital region, particularly in young, sexually active individuals. Perianal presentation is less common but significant, often linked to specific sexual practices. Bisexual men represent a unique demographic concerning STI risk factors and require careful assessment. This report details the diagnosis and management of perianal CA in a young bisexual male, emphasizing the diagnostic utility of clinical assessment, sexual history, and histopathology.
Case presentation: A 24-year-old Indonesian bisexual male presented with a three-month history of progressively enlarging, asymptomatic perianal nodules. He reported unprotected receptive anal intercourse with a male partner five months prior. Examination revealed multiple skin-colored, verrucous papules in the perianal region. HIV and syphilis screenings were negative. Histopathological examination of a biopsy specimen confirmed CA, showing parakeratosis, papillomatosis, acanthosis, and koilocytosis.
Conclusion: Treatment with 90% trichloroacetic acid (TCA) combined with cauterization resulted in significant clinical improvement at one-week follow-up. This case highlights the importance of obtaining a thorough, non-judgmental sexual history, recognizing characteristic lesion morphology, and utilizing histopathology for definitive diagnosis in managing perianal CA, particularly in populations with diverse sexual practices
Harnessing the Power of Nature: Ananas comosus Extract Gel as an Alternative Topical Treatment for Grade 2 Burn Wounds
Background: Burn injuries remain a significant global health challenge, often leading to complications such as infection and delayed healing. Conventional treatments can be costly and may have side effects, prompting exploration into natural therapeutic alternatives. Ananas comosus (pineapple), rich in the enzyme bromelain, has demonstrated anti-inflammatory and wound-healing properties, suggesting its potential as a topical agent for burn wounds. This study aimed to evaluate the efficacy of a topical gel formulated from Ananas comosus extract in promoting the healing of grade 2 burn wounds in a Wistar rat model by assessing its impact on wound diameter and the levels of pro-inflammatory cytokines Interleukin-1 beta (IL-1β) and Interleukin-6 (IL-6).
Methods: A true experimental study with a post-test only control group design was conducted using 30 male Wistar rats. Grade 2 burn wounds were induced on the dorsum of the rats. The rats were randomly assigned to six groups (n=5 per group): a normal control (KN, no treatment), negative control (K-), a positive control (K+, silver plus alginate hydrogel), and three treatment groups receiving topical Ananas comosus extract gel at concentrations of 15% (P1), 20% (P2), and 25% (P3) twice daily for 14 days. Wound diameter was measured on days 1, 3, 6, 9, 12, and 14 using the ImageJ application. On day 15, tissue samples were collected for IL-1β and IL-6 quantification via ELISA. Data were analyzed using Kruskal-Wallis and Mann-Whitney U tests for wound diameter, and One-Way ANOVA with LSD post-hoc test for cytokine levels, with p<0.05 considered significant.
Results: Significant differences in burn wound diameter and levels of IL-1β and IL-6 were observed among the groups (p<0.05). The P2 group (20% pineapple extract gel) exhibited the most significant reduction in wound diameter compared to the negative control and was comparable to the positive control group. This group also showed a marked decrease in IL-1β and IL-6 levels, with IL-1β levels similar to the positive control and IL-6 levels significantly lower than the untreated group and approaching those of the positive control.
Conclusion: Topical application of 20% Ananas comosus extract gel effectively accelerated the healing of grade 2 burn wounds and reduced the levels of pro-inflammatory cytokines IL-1β and IL-6 in Wistar rats. These findings support the potential use of pineapple extract as an alternative herbal topical therapy for burn injuries. Further research is warranted to explore optimal formulations and clinical applications in humans
Navigating Frontal Lobe Arteriovenous Malformation Resection: A Case Report on TIVA with Propofol-Remifentanil TCI for Hemodynamic Stability and ICP Control
Background: Arteriovenous malformations (AVMs) located within the frontal lobe present considerable anesthetic challenges. These challenges arise from the critical functions governed by this brain region and the inherent risks associated with intracranial surgery, notably hemodynamic instability and the potential for elevated intracranial pressure (ICP). The utilization of Total Intravenous Anesthesia (TIVA) through Target-Controlled Infusion (TCI) systems for propofol and remifentanil provides a sophisticated strategy for achieving precise control over anesthetic depth and maintaining physiological homeostasis. This report offers a detailed account of such a case.
Case presentation: A 25-year-old male patient, classified as ASA III, presented with a right frontal lobe Spetzler-Martin Grade I AVM and was scheduled for elective microsurgical resection. The anesthetic management centered on a TIVA approach, employing propofol administered via an Eleveld TCI model (target concentration range: 2-5 µg/mL) and remifentanil via a Minto TCI model (target concentration range: 4-6 ng/mL). Comprehensive intraoperative monitoring included invasive arterial blood pressure and central venous pressure. Pharmacological adjuncts included mannitol, dexamethasone, and tranexamic acid. Throughout the procedure, stable intraoperative hemodynamics (target Mean Arterial Pressure [MAP] 70-90 mmHg) were successfully maintained, and intracranial pressure was effectively controlled, thereby facilitating the complete AVM resection. The patient was extubated in the post-operative period, demonstrated a stable neurological status, and was subsequently managed in the Intensive Care Unit (ICU).
Conclusion: A meticulously planned and executed TIVA-TCI regimen, featuring propofol and remifentanil, when integrated with thorough invasive monitoring and proactive pharmacological interventions, demonstrated effectiveness in preserving crucial hemodynamic stability and fostering optimal intracranial conditions. This comprehensive anesthetic strategy was instrumental in the successful surgical resection of a frontal lobe AVM and contributed to a favorable neurological outcome for the patient
Impact of Tocolytic Therapy on Cardiovascular Outcomes in Preterm Labor: A Systematic Review and Meta-Analysis
Background: Preterm labor is a significant cause of neonatal morbidity and mortality, and tocolytic therapy is often used to delay delivery and improve neonatal outcomes. However, tocolytic drugs can have adverse cardiovascular effects, including an increased risk of atrial fibrillation (AF). This meta-analysis aims to evaluate the impact of tocolytic therapy on cardiovascular outcomes in preterm labor, focusing on the risk of AF.
Methods: A systematic literature review was conducted following PRISMA guidelines. Relevant studies published between 2013 and 2024 were identified through PubMed, Scopus, ScienceDirect, and Cochrane Library. Studies evaluating the cardiovascular effects of tocolytic therapy in preterm labor were included. The primary outcome was the incidence of AF. Secondary outcomes included other cardiovascular adverse events.
Results: Ten studies met the inclusion criteria, comprising 550 pregnant women receiving tocolytic therapy. Tocolytic therapy was associated with a significantly increased risk of AF compared to no tocolytic therapy (mean difference 0.2, 95% CI 0.10-0.30). Nifedipine and ritodrine had a higher risk of AF compared to atosiban. The risk of AF was also higher in patients with pre-existing cardiovascular diseases.
Conclusion: Tocolytic therapy, particularly with nifedipine and ritodrine, increases the risk of AF in preterm labor. Atosiban appears to be a safer option for patients with cardiovascular risk factors. Careful consideration of the potential cardiovascular risks and benefits is crucial when making tocolytic therapy decisions
The Osteoprotective and Chondroprotective Effects of Moringa oleifera: A Systematic Literature Review
Background: Bone and joint disorders, particularly arthritis and osteoporosis, represent significant global health burdens, often managed with NSAIDs and steroids, which carry potential systemic side effects. Moringa oleifera, a plant rich in bioactive compounds, has emerged as a potential therapeutic alternative due to its reported biological activities, including anti-inflammatory and antioxidant effects. This systematic review aimed to evaluate the existing preclinical evidence regarding the osteoprotective (bone-protective) and chondroprotective (cartilage-protective) effects of Moringa oleifera.
Methods: A systematic literature search was conducted following PRISMA guidelines across PubMed, Science Direct, and Google Scholar databases for relevant English-language articles published between 2014 and 2024. Studies investigating the effects of Moringa oleifera extracts on bone or cartilage health in in vivo arthritis or bone defect models were included. Data on study design, intervention details, outcome measures, and key findings related to osteoprotection and chondroprotection were extracted and synthesized qualitatively.
Results: Seven preclinical in vivo studies met the inclusion criteria. The included studies demonstrated that various extracts of Moringa oleifera (leaf ethanol, aqueous, methanol) exerted significant anti-inflammatory effects, evidenced by reduced paw edema, lower arthritis scores, and decreased inflammatory markers like CRP. Anti-nociceptive effects were also observed. Chondroprotective effects were indicated by improved radiographic scores (reduced joint space narrowing), cartilage regeneration, reduced fibrillation, and preservation of chondrocytes in histopathological analyses. Osteoprotective effects included increased osteoblast numbers, improved trabecular bone microarchitecture, decreased osteoclast numbers, reduced bone resorption, and enhanced bone healing, particularly when combined with marine collagen.
Conclusion: Preclinical evidence strongly suggested that Moringa oleifera possesses significant osteoprotective and chondroprotective properties, mediated likely through its anti-inflammatory, anti-nociceptive, antioxidant, and direct cellular effects on bone and cartilage cells. Moringa oleifera holds potential as a supplementary or alternative therapeutic strategy for managing bone and joint diseases like arthritis and osteoporosis, although further rigorous clinical investigation is warranted