RESUMEN
Dengue fever is a global public health concern, especially in countries like Bangladesh. This study examines youth perceived dengue risk, and preventive practices, providing valuable insights into their behavior regarding this mosquito-borne disease. A cross-sectional survey was undertaken in various regions of the Dhaka district in Bangladesh. Face-to-face interviews were conducted with 1,358 participants using convenience sampling, spanning the period from September 2 to October 10, 2023. A semi-structured questionnaire covered informed consent, socio-demographic data, and questions about perceived dengue risk scale (12 items), and prevention practice (13 items). Participants' mean age was 22.02 ± 1.58 years. The average scores for perceived dengue risk, and prevention practices were found to be 51.39 ± 12.01 (out of 96), and 55.57 ± 14.55 (out of 104) respectively. Previous dengue history, history of other vector-borne diseases, gender, educational level, father's educational qualification, employment status, adequate sleep duration, father's occupation, etc. are factors associated with higher risk and prevention practices regarding dengue. The research underscores the importance of tailoring prevention strategies for different demographics, raising awareness, and promoting active engagement in preventive measures. These insights are crucial for developing effective public health policies and campaigns to combat dengue.
Asunto(s)
Dengue , Animales , Humanos , Adolescente , Adulto Joven , Adulto , Dengue/epidemiología , Dengue/prevención & control , Estudios Transversales , Bangladesh/epidemiología , Salud Pública , Encuestas y Cuestionarios , Conocimientos, Actitudes y Práctica en SaludRESUMEN
Despite many studies on host or viral gene expression, how the cellular proteome responds to internal or external cues during the infection process remains unclear. In this study, we used a Hepatitis B Virus (HBV) replication model and performed proteomic analyses to understand how HBV evades innate immunity as a function of cell cycle progression. Specifically, we performed proteomic analyses of HBV-replicating cells in G1/S and G2/M phases, as a function of IFN-α treatment. We identified that the conserved LSm (Like-Sm1-8) proteins were differentially regulated in HBV replicating cells treated with IFN-α. Specifically, in G2/M phase, IFN-α increased protein level of LSm1, the unique subunit of cytoplasmic LSm1-7 complex involved in mRNA decay. By contrast, IFN-α decreased LSm8, the unique subunit of nuclear LSm2-8 complex, a chaperone of U6 spliceosomal RNA, suggesting the cytoplasmic LSm1-7 complex is antiviral, whereas the nuclear LSm2-8 complex is pro-viral. In HBV replication and infection models, siRNA-mediated knockdown of LSm1 increased all viral RNAs. Conversely, LSm8 knockdown reduced viral RNA levels, dependent on N6-adenosine methylation (m6A) of the epsilon stem-loop at the 5' end of pre-Core/pregenomic (preC/pg) RNA. Methylated RNA immunoprecipitation (MeRIP) assays demonstrated reduced viral RNA methylation by LSm8 knockdown, dependent on the 5' m6A modification, suggesting the LSm2-8 complex has a role in mediating this modification. Interestingly, splicing inhibitor Cp028 acting upstream of the LSm2-8 complex suppressed viral RNA levels without reducing the 5' m6A modification. This observation suggests Cp028 has novel antiviral effects, likely potentiating IFN-α-mediated suppression of HBV biosynthesis.
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Virus de la Hepatitis B , ARN Viral , Antivirales/farmacología , Virus de la Hepatitis B/fisiología , Interferón-alfa/metabolismo , Proteómica , ARN Viral/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
OBJECTIVE: RNA helicase DDX5 is downregulated during HBV replication and poor prognosis HBV-related hepatocellular carcinoma (HCC). The objective of this study is to investigate the role of DDX5 in interferon (IFN) signalling. We provide evidence of a novel mechanism involving DDX5 that enables translation of transcription factor STAT1 mediating the IFN response. DESIGN AND RESULTS: Molecular, pharmacological and biophysical assays were used together with cellular models of HBV replication, HCC cell lines and liver tumours. We demonstrate that DDX5 regulates STAT1 mRNA translation by resolving a G-quadruplex (rG4) RNA structure, proximal to the 5' end of STAT1 5'UTR. We employed luciferase reporter assays comparing wild type (WT) versus mutant rG4 sequence, rG4-stabilising compounds, CRISPR/Cas9 editing of the STAT1-rG4 sequence and circular dichroism determination of the rG4 structure. STAT1-rG4 edited cell lines were resistant to the effect of rG4-stabilising compounds in response to IFN-α, while HCC cell lines expressing low DDX5 exhibited reduced IFN response. Ribonucleoprotein and electrophoretic mobility assays demonstrated direct and selective binding of RNA helicase-active DDX5 to the WT STAT1-rG4 sequence. Immunohistochemistry of normal liver and liver tumours demonstrated that absence of DDX5 corresponded to absence of STAT1. Significantly, knockdown of DDX5 in HBV infected HepaRG cells reduced the anti-viral effect of IFN-α. CONCLUSION: RNA helicase DDX5 resolves a G-quadruplex structure in 5'UTR of STAT1 mRNA, enabling STAT1 translation. We propose that DDX5 is a key regulator of the dynamic range of IFN response during innate immunity and adjuvant IFN-α therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Regiones no Traducidas 5'/genética , Antivirales/farmacología , Carcinoma Hepatocelular/metabolismo , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , ARN Helicasas DEAD-box/farmacología , Virus de la Hepatitis B , Hepatocitos/metabolismo , Humanos , Interferón-alfa/metabolismo , Interferón-alfa/farmacología , Neoplasias Hepáticas/metabolismo , Biosíntesis de Proteínas , ARN Helicasas/genética , ARN Helicasas/metabolismo , ARN Helicasas/farmacología , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Replicación ViralRESUMEN
OBJECTIVES: Health-related quality of life is increasingly used as an important measurement of treatment outcome. Here, quality of life parameters in renal transplant recipients were evaluated and compared with patients with chronic kidney disease on maintenance hemodialysis and with those who were not on dialysis. MATERIALS AND METHODS: This cross-sectional study included patients seen at a number of tertiary renal care hospitals (there were 15 renal transplant recipients, 20 patients on maintenance hemodialysis, and 28 patients with chronic kidney disease not on dialysis). Forty healthy individual were also included as the control group. Different biochemical parameters were analyzed. Quality of life was assessed with the KDQOL-SF-36 (version 1.3) questionnaire. RESULTS: Mean age was 39 ± 11 for transplant patients, 43 ± 11 years for patients on hemodialysis, 49 ± 12 years for patients with chronic kidney disease not on dialysis, and 34 ± 11 years for the healthy control group. Distribution of sex was similar. Transplant recipients had higher quality of life scores, with some scores similar to healthy controls patients, like physical function (P = .85) and social function (P = .25). Scores were 100 ± 12, 69 ± 27, 37 ± 28, and 91 ± 10 (P < .001) for physical function; 94 ± 12, 44 ± 17, 30 ± 14, and 69 ± 29 (P < .001) for pain; 99 ± 11, 61 ± 46, 24 ± 15, and 70 ± 28 (P < .001) for social function; and 91 ± 11, 51 ± 13, 40 ± 7, and 66 ± 11 (P < .001) for energy/fatigue in healthy control, chronic kidney disease patients not on dialysis, hemodialysis patients, and transplant recipients, respectively. CONCLUSIONS: Quality of life is poor in patients with chronic kidney disease. However, renal transplant can improve quality of life. Transplant patients showed many quality of life scores similar to healthy individuals.
Asunto(s)
Trasplante de Riñón , Calidad de Vida , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Adulto , Bangladesh , Estudios de Casos y Controles , Estudios Transversales , Femenino , Estado Funcional , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Salud Mental , Persona de Mediana Edad , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/psicología , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
The global prevalence of hyperlipidaemia is increasing rapidly and high dietary fat intake is a major risk factor for developing hyperlipidaemia. An in-vivo biological investigation was carried out on ethanolic extract of Momordica charantia, a plant belonging to the family Cucurbitaceae for the evaluation of antihyperlipidemic activity and serum uric acid reducing potential. In our study, 25 healthy male mice were selected randomly and grouped into 5 groups (5 animals in each group). Lipid and uric acid profile were estimated after 21 days of treatment by using the enzymatic colourimetric GPO-PAP method. Results showed that ethanolic extract of M. charantia at a dose of 200 mg/kg body weight showed significant (p < 0.05) cholesterol and triglyceride level reduction profile when co-administrated with 20% fat and normal feed respectively. Atorvastatin was used as standard. Data from pathological examination showed that the average weight of the heart of the mice was normal for every group when compared with control. Gr-2 (normal and extract feed) showed significant (p Ë 0.05) increased of liver and kidney weight rather than experimental groups; however, these values were lower than the values for the control group. Uric acid level determination revealed that the ethanolic extract of M. charantia reduced serum uric acid level both in experimental groups (Gr-2 and Gr-3). Thus a considerable correlation was found between serum uric acid reducing potentials of the present plant extract with a lipid-lowering profile. This plant can be further investigated thoroughly as a potential source of chemically interesting and biologically important drug candidates.
RESUMEN
Although white adipose tissue (WAT) stores triglycerides and contributes to obesity, brown adipose tissue (BAT) dissipates energy as heat. Therefore, browning of WAT is regarded as an attractive way to counteract obesity. Our previous studies have revealed that treatment with cryptotanshinone (CT) during adipogenesis of 3T3-L1 cells inhibits their differentiation. Here, we found that pretreatment of C3H10T1/2 mesenchymal stem cells with CT before exposure to adipogenic hormonal stimuli promotes the commitment of these mesenchymal stem cells to the adipocyte lineage as confirmed by increased triglyceride accumulation. Furthermore, CT treatment induced the expression of early B-cell factor 2 (Ebf2) and bone morphogenetic protein 7 (Bmp7), which are known to drive differentiation of C3H10T1/2 mesenchymal stem cells toward preadipocytes and to the commitment to brown adipocytes. Consequently, CT treatment yielded brown-adipocyte-like features as evidenced by elevated expression of brown-fat signature genes including Ucp1, Prdm16, Pgc-1α, Cidea, Zic1, and beige-cell-specific genes such as CD137, Hspb7, Cox2, and Tmem26. Additionally, CT treatment induced mitochondrial biogenesis through upregulation of Sirt1, Tfam, Nrf1, and Cox7a and increased mitochondrial mass and DNA content. Our data also showed that cotreatment with CT and BMP4 was more effective at activating brown-adipocyte-specific genes. Mechanistic experiments revealed that treatment with CT activated AMPKα and p38-MAPK via their phosphorylation: the two major signaling pathways regulating energy metabolism. Thus, these findings suggest that CT is a candidate therapeutic agent against obesity working via activation of browning and mitochondrial biogenesis in C3H10T1/2 mesenchymal stem cells.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Adipocitos Marrones/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Mitocondrias/metabolismo , Dinámicas Mitocondriales/efectos de los fármacos , Fenantrenos/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Células 3T3-L1 , Proteínas Quinasas Activadas por AMP/genética , Adipocitos Marrones/citología , Animales , Antígenos de Diferenciación/biosíntesis , Antígenos de Diferenciación/genética , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Sistema de Señalización de MAP Quinasas/fisiología , Células Madre Mesenquimatosas/citología , Ratones , Mitocondrias/genética , Dinámicas Mitocondriales/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/genéticaRESUMEN
The canonical Wnt/ß-catenin signaling not only features in many developmental processes but also recently emerged as an attractive negative regulator of differentiation of preadipocytes into adipocytes. Here, we show that ß-catenin signaling plays a distinct role in methyl gallate (MG)-mediated inhibition of 3T3-L1 adipocytes differentiation. We found that the expression of ß-catenin decreased after adipogenic hormonal induction, whereas incubation of the differentiating cells with a physiological concentration of MG during adipogenic hormonal induction significantly prevented ß-catenin degradation by activating Wnt signaling components such as Wnt1, Wnt10b, Fzd1, Fzd2, Lrp5, Lrp6, Dvl1, and Dvl2. Mechanistic experiments revealed that MG treatment during early adipocytic differentiation specifically inhibited degradation of ß-catenin caused by phosphorylation at serine-33. In addition, MG treatment led to phosphorylation of GSK3ß, which is one of ß-catenin-degrading enzymes. Consequently, MG treatment facilitated translocation of the stabilized ß-catenin from the cytoplasm to nucleus, and activates its target genes cyclin D1 and c-Myc. Furthermore, MG-induced stabilization of ß-catenin suppresses PPARγ expression. Moreover, pharmacological activation or inhibition of ß-catenin signaling during adipocytes differentiation decreased and increased, respectively, the level of the key adipogenic marker, PPARγ, and of its downstream targets, aP2 and adiponectin while MG treatment effectively reversed their expression level. Collectively, our data suggest that MG is a novel pharmacological stimulator of canonical Wnt/ß-catenin signaling, and therefore represents a promising therapeutic agent in obesity.
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Adipogénesis/efectos de los fármacos , Ácido Gálico/análogos & derivados , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismo , Células 3T3-L1 , Transporte Activo de Núcleo Celular/efectos de los fármacos , Adipocitos/citología , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipogénesis/genética , Animales , Western Blotting , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Núcleo Celular/metabolismo , Proteínas Dishevelled/genética , Relación Dosis-Respuesta a Droga , Receptores Frizzled/genética , Ácido Gálico/farmacología , Expresión Génica/efectos de los fármacos , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Ratones , Microscopía Confocal , PPAR gamma/metabolismo , Fosforilación/efectos de los fármacos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serina/metabolismo , Vía de Señalización Wnt/genética , Proteína Wnt1/genética , beta Catenina/genéticaRESUMEN
Methyl gallate (MG) is a derivative of gallic acid and a potent antioxidant. In this study, we confirmed that MG treatment effectively inhibits lipid accumulation, which occurred mostly in the early stages of adipogenesis. We also showed that shortly after adipogenic induction, MG facilitated a G0/G1 cell cycle arrest. Mechanistic studies revealed that MG treatment inhibited ERK1/2 phosphorylation, which is a key regulator of the G1- to S-phase transition. Furthermore, MG treatment prevented the adipogenic hormonal stimuli-induced inhibition of the cyclin-dependent kinase inhibitor p27Kip1 . This led to inhibition of the transcription factor E2F1 by preventing the phosphorylation of, and thereby activation of its destruction partner RB. MG treatment also downregulated factors that are upstream of RB-E2F1 signaling such as Cdk2, Cyclin E, Cdk4, and Cyclin D1 where Cyclin D3 level was unaffected. We also found that MG treatment markedly decreased the expression and phosphorylation of C/EBPß, by phosphorylating, and therefore inactivating, GSK3ß, which is a prerequisite for its DNA binding capacity, and thereby mitotic clonal expansion (MCE). Ultimately, MG treatment downregulates key terminal adipogenic transcription factors including C/EBPα, PPARγ, aP2 (Fabp4), and adiponectin. Moreover, MG also protects adipocytes from oxidative stress by alleviating intracellular reactive oxygen species and activating Nrf2, HO-1, and PRDX3. Thus, this study provides a mechanistic insight into the anti-adipogenic actions of MG. © 2016 BioFactors, 42(6):716-726, 2016.
Asunto(s)
Adipocitos Blancos/fisiología , Antioxidantes/farmacología , Diferenciación Celular/efectos de los fármacos , Ácido Gálico/análogos & derivados , Mitosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Adipocitos Blancos/efectos de los fármacos , Adipogénesis , Animales , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Puntos de Control del Ciclo Celular , Células Cultivadas , Evaluación Preclínica de Medicamentos , Ácido Gálico/farmacología , Humanos , Metabolismo de los Lípidos , Ratones , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Cryptotanshinone (CT), a major tanshinone found in Salvia miltiorrhiza Bunge (Lamiaceae), has various pharmacological effects such as antitumor, anti-inflammatory, and antioxidant properties. Despite its well-documented benefits in a wide range of diseases, the effect of CT on adipocyte differentiation has not been well characterized. PURPOSE: The present study was designed to determine the in vitro anti-adipogenic effect and underlying molecular mechanisms of CT using 3T3-L1 murine pre-adipocytes. METHODS: We measured the levels of intracellular triglyceride accumulation and mRNA and protein expression of key adipogenic transcription factors and their target genes. RESULTS: Treatment with CT drastically reduced lipid accumulation in a dose- and time-dependent manner. Molecular assays showed that CT effectively suppressed the expression of C/EBPß, C/EBPα, and PPARγ and of their target adipocyte-specific genes aP2, adiponectin, and GLUT4 but activated the expression of anti-adipogenic genes such as GATA2, CHOP10, and TNF-α. CT treatment also inhibited the phosphorylation of STAT3 in the early phase of adipogenesis. A small-interfering-RNA-mediated knock-down of STAT3 potentiated the anti-adipogenic effect of CT. CONCLUSION: Taken together, the results suggest that CT may be a good anti-adipogenic candidate because it regulates STAT3 during early adipogenesis.
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Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Fenantrenos/farmacología , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Células 3T3-L1 , Adiponectina/metabolismo , Animales , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Diferenciación Celular/efectos de los fármacos , Regulación de la Expresión Génica , Silenciador del Gen , Transportador de Glucosa de Tipo 4/metabolismo , Ratones , PPAR gamma/metabolismo , Fosforilación , ARN Interferente Pequeño/genética , Factor de Transcripción STAT3/genética , Salvia miltiorrhiza/química , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Delphinidin (Del) is a major anthocyanin that is widely found in pigmented fruits and vegetables. Herein, we investigated the antiadipogenic effect and the molecular mechanism by which Del affects 3T3-L1 preadipocyte differentiation. We found that Del effectively reduced intracellular lipid accumulation and promoted lipolysis while regulating the expression of adipogenic transcription factors and their target genes. This lipid lowering effect of Del was largely limited to the early phase of adipogenesis, which is governed by the delayed cell cycle progression due to G1 cell cycle arrest. Subsequently, Del suppressed the expression of early adipogenic transcription factors, such as C/EBPß and C/EBPδ, as well as that of intermediate markers, C/EBPα, PPARγ, and the PPARγ-target adipocyte markers adiponectin and aP2 (FABP4). Furthermore, Del treatment activated Wnt1, Wnt10b, the Wnt receptor Fzd2, and the coreceptors Lrp5/6, while it inactivated Gsk3ß, a member of the ß-catenin destruction complex. Moreover, Del treatment stabilized cytoplasmic ß-catenin levels and promoted its nuclear translocation, with subsequent activation of the expression of its downstream target genes, c-Myc and cyclin D1. Our findings therefore suggest that Del can effectively inhibit adipogenesis followed by the stabilization of ß-catenin during early 3T3-L1 differentiation via inhibition of its destructive complexes and activation of Wnt signaling, and may thus be a promising candidate for the prevention of metabolic diseases, including obesity.
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Antocianinas/administración & dosificación , Diferenciación Celular/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipogénesis/efectos de los fármacos , Adipogénesis/genética , Animales , Ciclo Celular/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , RatonesRESUMEN
Makgeolli lees (ML) has several physiological effects such as antioxidant, antidiabetic, and anticancer properties, but its biological functions have not been determined definitively. Here, we tested whether ML has a cytoprotective effect on paraquat (PQ)-induced oxidative stress in the human lung carcinoma cell line A549. At 0.1 mg/ml ML, viability of PQ-exposed A549 cells was restored by 12.4%, 18.5%, and 48.6% after 24, 48, and 72 h, respectively. ML also reduced production of the intracellular reactive oxygen species (ROS) that were generated by PQ treatment. Further experiments revealed that ML treatment enhanced the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) as well as ARE-GFP reporter activity. ML treatment also effectively increased the expression of NRF2's target genes NAD(P)H dehydrogenase quinone 1 (NQO1) and heme oxygenase 1 (HO-1). Moreover, we found that expression of cytoprotective genes, including glutathione peroxidases (GPXs), superoxide dismutase (SOD1), catalase (CAT), peroxiredoxin 3 (PRDX3), and peroxiredoxin 4 (PRDX4), was greatly enhanced by treatment with ML during PQ exposure. Taken together, the data suggest that treatment of PQ-exposed A549 cells with ML ameliorates cytotoxicity through induction of NRF2 expression and its target genes HO-1, NQO1, and other antioxidant genes. Thus, ML may serve as a functional food applicable to ROS-mediated human diseases.
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Antioxidantes , Citoprotección , Herbicidas/farmacología , Factor 2 Relacionado con NF-E2/genética , Estrés Oxidativo/efectos de los fármacos , Paraquat/farmacología , Vino , Catalasa/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Alimentos Funcionales , Genes Reporteros , Glutatión Peroxidasa/genética , Hemo-Oxigenasa 1/genética , Humanos , NAD(P)H Deshidrogenasa (Quinona)/genética , Factor 2 Relacionado con NF-E2/metabolismo , Peroxiredoxina III/genética , Peroxirredoxinas/genética , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/genéticaRESUMEN
BACKGROUND: Unlike the brain tuberculoma, tubercular osteomyelitis of the skull is very rare and not sufficiently described in the literature. Awareness of this entity makes diagnosis possible. CASE DESCRIPTIONS: Two unique cases of cranial and epidural tuberculosis (TB) with absence of intradural and brain involvement are presented. Both patients presented with scalp swellings but extending through the calvarium into the epidural space. Histologic/bacteriologic confirmation of tuberculosis was obtained from biopsy specimens. Magnetic resonance imaging (MRI) findings of this rare lesion are described for the first time. CONCLUSIONS: Inflammatory scalp lesions with skull involvement and epidural extension should be investigated for tuberculous etiology. With early diagnosis and a combination of surgical and medical management, all cases of skull tuberculosis are potentially curable.