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1.
Childs Nerv Syst ; 40(4): 1185-1192, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38071636

RESUMO

OBJECTIVE: To analyze the outcomes of hypofractionated stereotactic radiotherapy (HFSRT) for Spetzler Martin grades 4 and 5 arteriovenous malformations (AVMs) in a pediatric population. METHODS: Fourteen patients with Spetzler Martin (SM) grades IV and V large AVMs who underwent HFSRT between January 2013 and July 2019 were retrospectively reviewed. All patients received HFSRT at a dose of 30-36 Gy in 5 to 6 fractions. They were followed up annually with clinical and imaging assessments to evaluate obliteration rates. RESULTS: The median age at presentation was 15 years (range 8-21 years). Ten (71%) were SM grade 4 AVMs and the rest were SM grade 5 AVMs. The majority presented with headache (8 [57%]), and 3 (21%) presented with bleeding. The median nidus volume was 39.4 cc (IQR, 31.4-52.4). Two (14%) patients had infratentorial AVMs. All of them had deep venous drainage. The median clinical follow-up duration was 75 months (range 31-107 months). There was complete obliteration of the nidus in 3 (21%) patients with a median time to obliteration of 39 months. HFSRT resulted in a reduction of the AVM volume to 12 cc or less in nearly 70% of patients. None of the patients experienced re-bleeding. 79% reported an improvement in their symptoms. CONCLUSION: HFSRT is a highly effective treatment for high-grade AVMs in children, which can result in either complete elimination or significant reduction of the nidus volume or make it suitable for additional treatment, such as single-session stereotactic radiosurgery (SRS).


Assuntos
Malformações Arteriovenosas Intracranianas , Radiocirurgia , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Estudos Retrospectivos , Malformações Arteriovenosas Intracranianas/cirurgia , Radiocirurgia/métodos , Resultado do Tratamento , Hipofracionamento da Dose de Radiação , Seguimentos
2.
Br J Neurosurg ; 37(3): 453-456, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31208238

RESUMO

Intercostal nerves (ICN) are often utilized as donors for various neurotization procedures in brachial plexus injuries. ICN to musculocutaneous nerve (MCN) transfer is usually a standard in pan brachial plexus injuries, in order to restore flexion at the elbow. A tensionless co-aptation of the donor-recipient nerves often necessitates either a distal dissection of the ICNs where the number of fascicles is rather low or a proximal dissection, often at the cost of dissection of the serratus anterior digitation with a risk of later fibrosis and adhesion. We report two cases of pan brachial plexus injuries where ICN-MCN transfer was performed to restore elbow function. These patients underwent clinical and electrodiagnostic evaluation before surgery. We used the standard technique of harvesting ICNs 3-5, with our technical modification of "undercutting of rib" for increasing the donor length. The procedure was applied in two patients with pan brachial plexus injury (mean age = 23). Mean duration since the injury to surgery was ten months. Both patients underwent tensionless anastomosis with a combination of suture and fibrin glue co-aptation. While one patient had some improvement in elbow flexion, another one was under active rehabilitation protocol during follow-up. We found that undercutting of the ribs near serratus digitations can allow mobilization of the ICN from its groove, which in turn lengthens the donor nerve length without violating the serratus anterior digitations and without too anterior dissection of the nerve. It can be a viable option when a tensionless co-aptation at the axilla is otherwise not feasible intraoperatively.


Assuntos
Neuropatias do Plexo Braquial , Plexo Braquial , Transferência de Nervo , Humanos , Adulto Jovem , Adulto , Nervo Musculocutâneo/cirurgia , Transferência de Nervo/métodos , Plexo Braquial/cirurgia , Plexo Braquial/lesões , Nervos Intercostais/cirurgia , Neuropatias do Plexo Braquial/cirurgia , Costelas/cirurgia , Recuperação de Função Fisiológica
3.
Neurol India ; 66(5): 1434-1446, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233019

RESUMO

INTRODUCTION: Petroclival meningiomas are based on or arising from the petro-clival junction in upper two-thirds of clivus, medial to the fifth cranial nerve. This study focuses on the surgical experience in resecting large-giant tumors >3.5 in size predominantly utilizing middle fossa approaches. MATERIAL AND METHODS: 33 patients with a large or a giant petroclival meningioma (size >3.5 cm) were included. Clinical features, preoperative radiological details, operative findings, and postoperative clinical course at the follow-up visit were reviewed. Group A tumors (n = 17,51.5%) were sized 3.5cm-5cm, and Group B (n = 16,48.48%) tumors were of size >5 cm. Extent of resection was described as 'gross total' (no residual tumor), 'near total' (<10% residual tumor) and 'subtotal resection' (>10% residual tumor). Glasgow outcome scale (GOS) quantitatively scored postoperative neurological outcome (mean follow up: 35.77months; range 1-106 months). RESULTS: 25 (75.8%) patients had tumour extension into both supratentorial and infratentorial compartments. Extension into Meckel's cave (n = 25,75.8%), cavernous sinus (n = 17,48.4%], sphenoid sinus (n = 12,38.7%] and suprasellar area [12,38.7%] was often seen. In 31 (93.9%) patients, the tumor crossed the midline in the premedullary, prepontine, and interpeduncular cisterns. In 20 (60.6%) patients, the tumour extended below and posterior to the internal auditory meatus (IAM), while in 13 (39.4%) patients, the tumor was located above and anterior to the IAM. Kawase's approach was the most commonly used approach in 16 (48.48%) patients and resulted in maximum tumor resection. Other approaches included half-and-half (trans-Sylvian with subtemporal) [n = 6, 18.18%]; frontotemporal craniotomy with orbitozygomatic osteotomy [n = 1, 3%] and retromastoid suboccipital craniectomy (RMSO) [n = 7, 21.21%]. In 2 (6.06%) patients, staged anterior petrosectomy with RMSO; and, in 1, staged presigmoid with half-and-half approach was used. Gross total excision was achieved in 12 (36.36%), near-total excision in 15 (45.45%) and subtotal excision in 6 (18.18%) patients. 20 (60.6%) patients had a good functional outcome; 6 patients succumbed due to meningitis, pneumonitis, perforator injury or a large tumor recurrence. CONCLUSIONS: Half-and-half approach was used in tumors with middle and posterior cranial fossae components often extending to the suprasellar region. Kawase's anterior petrosectomy was utilized in resecting tumors with predominant posterior fossa component (along with a small middle fossa component) that was crossing the midline anterior to the brain stem, and mainly situated superomedial to the IAM. Tumors confined to the posterior fossa, that extended laterally and below the IAM were resected utilizing the RMSO approach. Occasionally, a combination of these approaches was used. Middle fossa approaches help in significantly avoiding morbidity by an early devascularisation and decompression of the tumor. In tumors lacking a plane of cleavage, a thin rim of capsule of tumor may be left to avoid brain stem signs.


Assuntos
Fossa Craniana Média/cirurgia , Meningioma/cirurgia , Neoplasias da Base do Crânio/cirurgia , Nervo Trigêmeo/cirurgia , Adulto , Fossa Craniana Média/patologia , Craniotomia/métodos , Feminino , Humanos , Masculino , Meningioma/patologia , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Base do Crânio/patologia , Nervo Trigêmeo/patologia
4.
Neurol India ; 66(3): 779-796, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29766943

RESUMO

INTRODUCTION: Hemangioblastomas [75% sporadic, 25% with Von Hippel Lindau (VHL) disease] are highly vascular, benign lesions. The surgical nuances, management, and complication avoidance in brain-stem hemangioblastomas (BHs) have been studied. MATERIAL AND METHODS: Over 18 years, 27(mean age: 29 years; range 15-60 years) consecutive cases of BH underwent microsurgical excision. All patients were assessed clinico-radiologically for neurological deficits and screened for VHL disease. Outcome of the patients was based on Karnofsky Performance Status scale (KPS). RESULTS: 12 out of 19 (70.4%) patients with hydrocephalus underwent a cerebrospinal fluid (CSF) diversion procedure. Lower cranial nerve palsy was present in 10 (37%) patients and motor weakness in 13 (48%). The tumours [mean size 3.34 ± 1.06 cm, range: 1.4-5.5 cm; 11 solid, rest solid-cystic; 18 (66.7%) subpial and 9 (33.33%) intramedullary] were divided into four categories based on size: A: <2 cm (n = 5,18.5%); B: 2-3 cm (n = 10,37%); C: 3-4 cm (n = 6,22.2%); D: >4 cm (n = 6,22.2%). Their location was at posterior cervicomedullary junction (n = 12); pontomedullary junction (n = 7); pons (n = 3), medulla (n = 3) and ponto-mesencephalic region (n = 2). Multiple flow voids were seen in >50% patients with tumour >2 cm. 5 patients had syringomyelia; and, 8 had diffuse cervical cord expansion. Two patients with a large vascular tumour underwent preoperative embolization. Six patients had VHL disease; one underwent bilateral adrenalectomy for refractory hypertension; and, the another, nephrectomy for renal cell carcinoma. Twenty-six patients underwent a midline suboccipital craniectomy; and, 1 with a cerebellopontine angle tumour, a retromastoid craniectomy. 15 patients underwent total excision; 10 patients, near-total (<10% remaining) excision, and 2 patients, a subtotal (>10% remaining)) excision. Three patients (2 with VHL disease) expired due to exsanguinating hemorrhage, spreading venous thrombosis and aspiration pneumonitis, respectively. At follow-up visit (median: 25 ± interquartile range 2-56months), 17 patients had improved KPS, 4 remained in same status and 3 (recently operated, on tracheostomy) had worsened KPS. CONCLUSIONS: Significant improvement is achievable in neurological status in patients following successful extirpation of a brain-stem hemangioblastoma, despite a turbulent perioperative period. Leaving tumour capsule adherent to the brain-stem often helps in preserving brain-stem function. Postoperatively, the patients should be monitored for their respiratory and lower cranial nerve status to prevent aspiration pneumonitis.


Assuntos
Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/cirurgia , Hemangioblastoma/patologia , Hemangioblastoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
5.
J Immunol ; 190(1): 48-57, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23180817

RESUMO

Particular alleles of HLA contribute to disease susceptibility and severity in many autoimmune conditions, but the mechanisms underlying these associations are often unknown. In this study, we demonstrate that the shared epitope (SE), an HLA-DRB1-coded sequence motif that is the single most significant genetic risk factor for erosive rheumatoid arthritis, acts as a signal transduction ligand that potently activates osteoclastogenesis, both in vitro and in vivo. The SE enhanced the production of several pro-osteoclastogenic factors and facilitated osteoclast (OC) differentiation in mouse and human cells in vitro. Transgenic mice expressing a human HLA-DRB1 allele that code the SE motif demonstrated markedly higher propensity for osteoclastogenesis and enhanced bone degradation capacity ex vivo. In addition, the SE enhanced the differentiation of Th17 cells expressing the receptor activator for NF-κB ligand. When the two agents were combined, IL-17 and the SE enhanced OC differentiation synergistically. When administered in vivo to mice with collagen-induced arthritis, the SE ligand significantly increased arthritis severity, synovial tissue OC abundance, and bone erosion. Thus, the SE contributes to arthritis severity by activating an OC-mediated bone-destructive pathway. These findings suggest that besides determining the target specificity of autoimmune responses, HLA molecules may influence disease outcomes by shaping the pathogenic consequences of such responses.


Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/metabolismo , Mediadores da Inflamação/fisiologia , Transdução de Sinais/imunologia , Alelos , Animais , Artrite Reumatoide/genética , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Células Cultivadas , Epitopos de Linfócito T/imunologia , Predisposição Genética para Doença , Cadeias HLA-DRB1/fisiologia , Humanos , Mediadores da Inflamação/metabolismo , Ligantes , Camundongos , Camundongos Transgênicos , Osteoclastos/imunologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Transdução de Sinais/genética , Células Th17/imunologia , Células Th17/metabolismo
6.
Apoptosis ; 19(1): 269-84, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24220853

RESUMO

Despite the use of new generation target specific drugs or combination treatments, drug-resistance caused by defective apoptosis signaling remains a major challenge in cancer treatment. A common apoptotic defect in drug-resistant tumor is the failure of cancer cells to undergo Bax/Bak-dependent mitochondrial permeabilization due to impaired signaling of Bcl-2 family proteins. Therefore, Bax and Bak-independent caspase-activating compounds appear to be effective in killing such tumor cells. An image-based cellular platform of caspase sensors in Bax and Bak deficient background allowed us to identify several potential Bax/Bak-independent caspase-activating compounds from a limited high-throughput compound screening. FRET-based caspase sensor probe targeted at the nucleus enabled accurate and automated segmentation, yielding a Z-value of 0.72. Some of the positive hits showed promising activity against drug-resistant human cancer cells expressing high levels of Bcl-2 or Bcl-xL. Using this approach, we describe thiolutin, CD437 and TPEN as the most potentially valuable drug candidates for addressing drug-resistance caused by aberrant expression of Bcl-2 family proteins in tumor cells. The screen also enables the quantification of multiparameter apoptotic events along with caspase activation in HTS manner in live mode, allowing characterization of non-classical apoptosis signaling.


Assuntos
Antineoplásicos/farmacologia , Caspases/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Transferência Ressonante de Energia de Fluorescência/métodos , Ensaios de Triagem em Larga Escala/métodos , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína X Associada a bcl-2/genética
7.
Blood ; 119(8): 1888-96, 2012 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-22223826

RESUMO

Multiple myeloma (MM) is an incurable B-cell malignancy in which the marrow microenvironment plays a critical role in our inability to cure MM. Marrow stromal cells in the microenvironment support homing, lodging, and growth of MM cells through activation of multiple signaling pathways in both MM and stromal cells. Recently, we identified annexin II (AXII) as a previously unknown factor produced by stromal cells and osteoclasts (OCL) that is involved in OCL formation, HSC and prostate cancer (PCa) homing to the BM as well as mobilization of HSC and PCa cells. AXII expressed on stromal cells supports PCa cell lodgment via the AXII receptor (AXIIR) on PCa cells, but the role of AXII and AXIIR in MM is unknown. In this study, we show that MM cells express AXIIR, that stromal/osteoblast-derived AXII facilitates adhesion of MM cells to stromal cells via AXIIR, and OCL-derived AXII enhances MM cell growth. Finally, we demonstrate that AXII activates the ERK1/2 and AKT pathways in MM cells to enhance MM cell growth. These results demonstrate that AXII and AXIIR play important roles in MM and that targeting the AXII/AXIIR axis may be a novel therapeutic approach for MM.


Assuntos
Anexina A2/metabolismo , Medula Óssea/metabolismo , Proliferação de Células , Mieloma Múltiplo/metabolismo , Receptores de Peptídeos/metabolismo , Animais , Anexina A2/genética , Anexina A2/farmacologia , Western Blotting , Células da Medula Óssea/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Células Cultivadas , Microambiente Celular , Técnicas de Cocultura , Humanos , Camundongos , Camundongos Knockout , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Osteoclastos/metabolismo , Fosforilação/efeitos dos fármacos , Ligação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Receptores de Peptídeos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais
8.
J Neurosci Rural Pract ; 15(1): 134-136, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476419

RESUMO

Intracranial hypotension (IH) represents a syndrome secondary to low cerebrospinal fluid pressure. This case of IH following a lumbar drain inserted before the excision of a left intraconal lesion, leading to recurrent post-operative unilateral subdural and extradural collections, was treated successfully with the evacuation of the collection and simultaneous epidural blood patch (EBP) injection. Our report provides an important perspective on the management of IH with recurrent intracranial collections and reiterates that IH should be considered when dealing with recurrent unilateral intracranial collections in the post-operative period. Evacuation with a simultaneous EBP is an effective strategy for managing IH.

9.
Cureus ; 16(4): e59128, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38803769

RESUMO

The adoption of Electronic Health Records (EHRs) and the establishment of Health Information Exchange (HIE) systems have significantly transformed healthcare delivery and management. This study presents a comprehensive bibliometric analysis and visualization of the landscape surrounding EHRs and HIE to provide insights into the current state and emerging trends in this field. Leveraging advanced bibliometric methodologies, including co-citation analysis, keyword co-occurrence analysis, and network visualization techniques, we systematically map the scholarly literature spanning several decades. Our analysis reveals key thematic clusters, influential publications, prolific authors, and collaborative networks within the domain of EHRs and HIE. Furthermore, we identify significant research gaps and areas for future exploration, including interoperability challenges, privacy concerns, and the integration of emerging technologies such as artificial intelligence and blockchain. The findings of this study offer valuable insights for researchers, policymakers, and healthcare practitioners seeking to navigate and contribute to the ongoing evolution of EHRs and HIE systems, ultimately enhancing the quality, efficiency, and accessibility of healthcare services.

10.
J Craniovertebr Junction Spine ; 15(1): 110-113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38644918

RESUMO

Ewing's sarcoma is a rare and highly aggressive bone tumor primarily affecting children and adolescents. It commonly presents in the pelvic and axial skeleton, with sacral involvement posing unique challenges due to its intricate anatomical location. This report details the case of an 18-year-old male with sacral Ewing's sarcoma, emphasizing the diagnostic, surgical, and reconstructive aspects of management. The patient presented with lower back pain, lower limb weakness, and urinary incontinence, which prompted an extensive diagnostic evaluation. Magnetic resonance imaging and computed tomography scans revealed a large lytic mass extending from the S2 vertebra to the coccyx invading the presacral space. Biopsy confirmed the diagnosis of Ewing's sarcoma, characterized by the EWS-FLI1 type 1 translocation. A multidisciplinary team comprising neurosurgeons, colorectal surgeons, and plastic surgeons was formulated. En bloc resection of the tumor, lumbopelvic fixation, and soft-tissue reconstruction using bilateral gluteus maximus advancement flaps were successfully performed. The procedure aimed to address both the oncological and functional aspects of the patient's condition. Chemotherapy and radiotherapy were administered as adjuvant therapies. At 2-year follow-up, the patient was ambulating independently with no residual tumor on imaging. This case highlights the complex nature of sacral Ewing's sarcoma and underscores the importance of a multidisciplinary approach. The described surgical technique, including the innovative use of gluteus maximus advancement flaps for soft-tissue reconstruction, contributes to reducing wound complications and promoting successful patient outcomes. The presented approach serves as a valuable addition to the armamentarium of treatment options for this challenging malignancy.

11.
World Neurosurg ; 178: e731-e740, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37544604

RESUMO

OBJECTIVE: To study patients with spinal arachnoid cysts, who underwent cyst excision with dural defect repair or marsupialization, and their outcomes. METHODS: The retrospective analysis involved reviewing the records of 38 patients who underwent surgical treatment for spinal arachnoid cysts in the Department of Neurosurgery at Christian Medical College, Vellore, between August 2004 and December 2022. The study examined the demographics, clinical presentation, imaging, surgical intervention, and outcomes of these patients. RESULTS: The majority of patients in the study were male (29/38, with 76.3%) and the thoracic region was the most common location for the cyst (17, with 44.7%). Weakness was the primary complaint and 94.7% of patients had myelopathy. The bladder was affected in 13 patients (34.2%). Of the 38 patients, 26 (71%) had cysts in extradural locations, while the rest were intradural. In total, 45.5% of intradural cysts were located in the ventral region. Seventeen (65.4%) had dural defects along the root sleeve and 29 (76.3%) underwent complete excision. All extradural cysts underwent complete excision and repair of the dural defect. Thirty patients (78.9%) experienced improved outcomes with reduced spasticity and improved weakness. One patient developed new-onset weakness postoperatively due to epidural hematoma. The mean follow-up period was 41 months and one patient experienced a recurrence. CONCLUSIONS: Spinal arachnoid cyst is a rare benign spinal condition that is typically treated with surgery in symptomatic patients. Surgical intervention may involve either the excision of the cyst or marsupialization.

12.
BMJ Case Rep ; 16(5)2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37130633

RESUMO

Paediatric Bow Hunter's syndrome (BHS), or rotational vertebral artery syndrome, is a rare cause of posterior circulation insufficiency in children. It results from mechanical obstruction of the vertebral artery by the transverse process of cervical vertebrae resulting in vertebrobasilar insufficiency during the neck rotation to the sides. Paediatric dilated cardiomyopathy (DCM) is a rare myocardial disease that presents with ventricular dilatation and cardiac dysfunction. This case report describes the successful anaesthetic management of an boy with BHS due to atlantoaxial dislocation and DCM. The child was anaesthetised by keeping the following anaesthetic goals in mind such as maintenance of the heart rate, rhythm, preload, afterload and contractility close to the baseline for both DCM and BHS. Haemodynamic management with optimal fluids, inotrope and a vasopressor and titrating its volume and doses using multimodal haemodynamic monitoring while keeping both cardio and neuroprotective strategies, and the multimodal analgesia techniques helped the child for faster recovery.


Assuntos
Cardiomiopatia Dilatada , Mucopolissacaridose II , Fusão Vertebral , Insuficiência Vertebrobasilar , Masculino , Humanos , Criança , Mucopolissacaridose II/complicações , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/cirurgia , Artéria Vertebral , Insuficiência Vertebrobasilar/etiologia , Fusão Vertebral/efeitos adversos
13.
J Cell Biochem ; 113(1): 220-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21898543

RESUMO

The role of erythropoietin (Epo) and Epo/Epo receptor (EpoR) signaling pathways for production of red blood cells are well established. However, little is known about Epo/EpoR signaling in non-hematopoietic cells. Recently, we demonstrated that Epo activates JAK/STAT signaling in hematopoietic stem cells (HSCs), leading to the production of bone morphogenetic protein 2 (BMP2) and bone formation and that Epo also directly activates mesenchymal cells to form osteoblasts in vitro. In this study, we investigated the effects of mTOR signaling on Epo-mediated osteoblastogenesis and osteoclastogenesis. We found that mTOR inhibition by rapamycin blocks Epo-dependent and -independent osteoblastic phenotypes in human bone marrow stromal cells (hBMSCs) and ST2 cells, respectively. Furthermore, we found that rapamycin inhibits Epo-dependent and -independent osteoclastogenesis in mouse bone marrow mononuclear cells and Raw264.7 cells. Finally, we demonstrated that Epo increases NFATc1 expression and decreases cathepsin K expression in an mTOR-independent manner, resulting in an increase of osteoclast numbers and a decrease in resorption activity. Taken together, these results strongly indicate that mTOR signaling plays an important role in Epo-mediated bone homeostasis.


Assuntos
Eritropoetina/metabolismo , Osteogênese/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Desenvolvimento Ósseo/genética , Desenvolvimento Ósseo/fisiologia , Osso e Ossos/metabolismo , Osso e Ossos/fisiologia , Catepsina K/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos , Fatores de Transcrição NFATC/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Receptores da Eritropoetina/metabolismo , Transdução de Sinais , Sirolimo/farmacologia , Células Estromais/metabolismo
15.
J Endocrinol ; 248(2): 237-247, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33289686

RESUMO

Corticosteroids are increasingly being used during the peri-implantation period to treat women with repeated IVF failure and recurrent miscarriage. However, the direct effects of prednisolone (PRDL), one of the commonly used corticosteroids on early embryo development is not understood. To mimic the possible clinical scenario and to understand the embryonic response to direct PRDL exposure, this pilot study was conducted in a mouse model. Cleavage stage embryos exposed to 3 and 30 µM PRDL in vitro were assessed for peri-implantation developmental potential, genetic integrity, inner cell mass (ICM) proliferation and pluripotency markers in the proliferated ICM cells. Exposure to 30 µM PRDL delayed the embryonic progression beyond compaction (P < 0.05) in comparison to vehicle control and, had reduced total cell number (P < 0.001) than all other groups. In addition, 30 µM PRDL exposure resulted in poor hatching potential (P < 0.05) and increased apoptosis in blastocysts (P < 0.05) compared to 3 µM PRDL. On the other hand, completely formed ICM outgrowths were significantly higher (P < 0.05) in 3 µM PRDL compared to control. However, no significant differences were observed in the expression of pluripotency genes. In conclusion, the trend observed in embryos exposed to PRDL in vitro provides important information concerning the use of this drug when treating patients at the peri-implantation phase of IVF cycles. However, the clinical value of this observation on human embryo development needs further research.


Assuntos
Embrião de Mamíferos/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Prednisolona/efeitos adversos , Animais , Avaliação Pré-Clínica de Medicamentos , Implantação do Embrião , Feminino , Infertilidade Feminina/tratamento farmacológico , Masculino , Camundongos , Projetos Piloto
16.
Calcif Tissue Int ; 86(2): 154-62, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19953231

RESUMO

Fibronectin (FN) fragments found in chronic inflammatory diseases, including periodontal disease and arthritis, may contribute to tissue destruction in part via induction of matrix metalloproteinases (MMPs). We previously showed that the 120-kDa FN fragment containing the central cell binding domain (120FN) dose dependently induces MMP-1 (collagenase-1) in human periodontal ligament (PDL) cells, whereas intact FN did not elicit this response. Recently, we found that an increase in MMP-1 expression is accompanied by a decreased osteoblastic phenotype in PDL cells. We hypothesized that 120FN inhibits osteoblastic differentiation of PDL cells by inducing MMP-1. Effects of increasing concentrations of 120FN on MMP-1 expression and on osteoblastic markers were assessed in cultured PDL cells using Western blotting, qRT-PCR, and collagen degradation and alkaline phosphatase (AP) activity assays. The 120FN dose dependently increased MMP-1 expression and activity, concomitant with a decrease in AP activity. The increase in collagenase activity was largely attributed to increased MMP-1 expression. Concurrent with the decrease in AP activity, the 120FN reduced baseline and dexamethasone-induced gene expression of specific osteoblastic markers, Runx2 and osteonectin, and diminished mineralized nodule formation. Finally, siRNA inhibition of 120FN-induced MMP-1 reduced collagenase expression and rescued the AP phenotype to baseline levels. These findings suggest that disease-associated 120FN, in addition to having direct effects on tissue destruction by upregulating MMPs, could contribute to disease progression by impeding osteoblastic differentiation of osteogenic PDL cells and, consequently, diminish bone regeneration.


Assuntos
Diferenciação Celular/fisiologia , Matriz Extracelular/enzimologia , Metaloproteinase 1 da Matriz/metabolismo , Osteoblastos/metabolismo , Ligamento Periodontal/metabolismo , Células-Tronco/metabolismo , Regeneração Óssea/fisiologia , Reabsorção Óssea/enzimologia , Reabsorção Óssea/fisiopatologia , Células Cultivadas , Colágeno/metabolismo , Colagenases/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Relação Dose-Resposta a Droga , Humanos , Metaloproteinase 1 da Matriz/genética , Osteoblastos/citologia , Osteonectina/genética , Fragmentos de Peptídeos/farmacologia , Doenças Periodontais/enzimologia , Doenças Periodontais/fisiopatologia , Ligamento Periodontal/citologia , Estrutura Terciária de Proteína/fisiologia , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Células-Tronco/citologia
17.
Asian J Neurosurg ; 14(2): 553-556, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31143281

RESUMO

We report the case of a 30-year-old female with a Sylvian fissure, white epidermoid which was radiologically looking like a dermoid cyst. The female presented with a headache with no neurological deficits. On radiology, the lesion was in Sylvian fissure, T1 hyperintense, T2 hypointense, and with minimal diffusion restriction medially. Hence a preoperative impression of dermoid cyst was made, a quite uncommon location. Intraoperatively, the classical pearly-white flaky appearance of epidermoid was seen which was confirmed histopathologically. White epidermoids appearing so because of high protein content are a rarity and are more likely to cause aseptic meningitis in the event of intraoperative spillage. Differentiating between a dermoid cyst and white epidermoid preoperatively and radiologically is difficult. Dermoids show diffusion restriction and are usually midline, whereas white epidermoids do not show diffusion restriction and are usually lateral. This is the first report of a white epidermoid in Sylvian fissure to the best of our knowledge.

18.
World Neurosurg ; 129: 105-109, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31150861

RESUMO

BACKGROUND: Iniencephaly is an extremely rare congenital neural tube defect (NTD) involving the occipital region with rachischisis of the cervicothoracic spine and fixed retroflexion deformity of the head. It affects an estimated 0.1-10 out of 10,000 pregnancies and carries a dismal prognosis. Most affected children are either stillborn or perish within a few hours of delivery. Pathological and postmortem studies of iniencephaly significantly outnumber the limited amount of literature available on patients surviving with this disorder. To date, surgical repair has been attempted in only 3 of the 8 patients with iniencephaly who have survived long-term. Thus, a huge knowledge gap remains regarding the neurosurgical nuances and postsurgical outcomes in iniencephaly. CASE DESCRIPTION: A 4-year-old girl presented with soft, fluctuant swelling in the suboccipital region and was subsequently diagnosed with iniencephaly. She underwent a successful surgical repair of the encephalocele with dural plication. No recurrence of swelling or new neurologic deficits were noted at a 1-year follow-up. CONCLUSION: Iniencephaly is a complex NTD associated with high perinatal mortality that requires a vigilant antenatal diagnosis. Surgical repair may be attempted in the lucky few survivors after a thorough evaluation of the anomaly.


Assuntos
Defeitos do Tubo Neural/cirurgia , Procedimentos Neurocirúrgicos/métodos , Pré-Escolar , Feminino , Humanos , Sobreviventes , Resultado do Tratamento
19.
J Craniovertebr Junction Spine ; 9(2): 122-129, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30008531

RESUMO

BACKGROUND: There is growing indications of minimally invasive spine surgery. The inherent attitude and institutive learning curve limit transition from standard open surgery to minimally invasive surgery demanding understanding of new instruments and correlative anatomy. MATERIALS AND METHODS: In this prospective study, 80 patients operated for lumbar disc prolapse were included in the study (between January 2016 and March 2018). Fifty patients (Group A) operated by various minimally invasive spine surgery (MISS) techniques for herniated disc disease were compared with randomly selected 30 patients (Group B) operated between the same time interval by standard open approach. Surgical outcome with Oswestry Disability Index (ODI) and patient satisfaction score was calculated in pre- and postoperative periods. RESULTS: Mean preoperative ODI score in Group A was 31.52 ± 7.5 standard deviation (SD) (range: 6"46; interquartile range [IQR]: 8; median: 32.11) and postoperative ODI score was 9.20 ± 87.8 SD (range: 0"38; IQR: 11; median: 6.67). Mean preoperative ODI score in Group B was 26.47 ± 4.9 SD (range: 18"38; IQR: 4; median: 25) and postoperative ODI score was 12.27 ± 8.4 SD (range: 3"34; IQR: 12; median: 10.0). None of the patients was unsatisfied in either group. On comparing the patient satisfaction score among two groups, no significant difference (P = 0.27) was found. DISCUSSION: On comparing the change in ODI and preoperative ODI among both groups, we found a significant difference between the groups. It is worth shifting from open to MISS accepting small learning curve. The satisfaction score of MISS in early transition period is similar to open procedure. CONCLUSION: The MISS is safe and effective procedure even in transition period for the central and paracentral prolapsed lumbar intervertebral disc treatment. The results are comparable, and patient satisfaction and symptomatic relief are not compromised.

20.
Asian J Neurosurg ; 13(2): 492-495, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29682070

RESUMO

Germ cell tumors (GCTs) are rare intracranial tumors with a strong predilection for children. Commonly, these tumors arise either in the suprasellar or the pineal region. The basal ganglia-thalamus complex represents a rare site of nonmidline intracranial GCTs. Such basal ganglionic GCTs have been reported to produce certain interesting clinico-radiological features, the knowledge of which may provide important diagnostic clues preoperatively. We present the case of a 9.5-year-old boy who presented with right hemiparesis and precocious puberty. Imaging revealed a heterogeneously enhancing mass involving the left capsuloganglionic region, sparing the thalamus. There was little perilesional edema and midline shift. Because of the deep location of the mass and a lack of mass effect, a neuronavigation-guided tumor biopsy was performed which unraveled a pure germinoma. The child was referred for adjuvant radiotherapy following an uneventful postoperative course. At the time of writing the report, the child was on radiotherapy and doing well.

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