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1.
Antimicrob Agents Chemother ; : e0008424, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758004

RESUMEN

When using amikacin to treat Mycobacterium avium complex pulmonary disease (MAC-PD), a minimum inhibitory concentration resistance breakpoint of ≥64 mcg/mL is recommended. We explored whether amikacin resistance characterized by phenotypic drug susceptibility testing was associated with clinical outcomes or mutational resistance in a retrospective cohort of patients with MAC-PD. Despite little aminoglycoside exposure, amikacin resistance was common in our MAC-PD patients but was not associated with worse outcomes or rrs gene mutations.

2.
J Gene Med ; 26(8): e3730, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39152771

RESUMEN

The uncontrolled growth and spread of cancerous cells beyond their usual boundaries into surrounding tissues characterizes cancer. In developed countries, cancer is the leading cause of death, while in underdeveloped nations, it ranks second. Using existing cancer diagnostic tools has increased early detection rates, which is crucial for effective cancer treatment. In recent decades, there has been significant progress in cancer-specific survival rates owing to advances in cancer detection and treatment. The ability to accurately identify precursor lesions is a crucial aspect of effective cancer screening programs, as it enables early treatment initiation, leading to lower long-term incidence of invasive cancer and improved overall prognosis. However, these diagnostic methods have limitations, such as high costs and technical challenges, which can make accurate diagnosis of certain deep-seated tumors difficult. To achieve accurate cancer diagnosis and prognosis, it is essential to continue developing cutting-edge technologies in molecular biology and cancer imaging.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias , Humanos , Detección Precoz del Cáncer/métodos , Neoplasias/diagnóstico , Neoplasias/terapia , Neoplasias/genética , Pronóstico , Biomarcadores de Tumor/genética , Resultado del Tratamiento
3.
Theor Appl Genet ; 137(1): 32, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38270625

RESUMEN

KEY MESSAGE: Mapping and fine mapping of bean anthracnose resistance genes is a continuous process. We report fine mapping of anthracnose resistance gene Co-18 which is the first anthracnose gene mapped to Pv10. The discovery of resistance gene is a major gain in the bean anthracnose pathosystem research. Among the Indian common bean landraces, KRC-5 exhibit high levels of resistance to the bean anthracnose pathogen Colletotrichum lindemuthianum. To precisely map the anthracnose resistance gene, we used a Recombinant Inbred Line (F2:9 RIL) population (KRC-5 × Jawala). The inheritance test revealed that KRC-5 carries a dominant resistance gene temporarily designated as Co-18. We discovered two RAPD markers linked to Co-18 among 287 RAPD markers. These RAPD markers were eventually developed into SCARs (Sc-OPR15 and Sc-OPF6) and flank Co-18 on chromosome Pv10 at a distance of 5.3 and 4.2 cM, respectively. At 4.0-4.1 Mb on Pv10, we detected a SNP (single-nucleotide polymorphism) signal. We synthesized 58 SSRs and 83 InDels from a pool of 135 SSRs and 1134 InDels, respectively. Five SSRs, four InDels, and two SCARs were used to generate the high-density linkage map, which led to the identification of two SSRs (SSR24 and SSR36) that are tightly linked to Co-18. These two SSRs flank the Co-18 to 178 kb genomic region with 13 candidate genes including five NLR (nucleotide-binding and leucine-rich repeat) genes. The closely linked markers SSR24 and SSR36 will be used in cloning and pyramiding of the Co-18 gene with other R genes to develop durable resistant bean varieties.


Asunto(s)
Phaseolus , Phaseolus/genética , Cicatriz , Técnica del ADN Polimorfo Amplificado Aleatorio , Mapeo Cromosómico , Genes Dominantes
4.
Cell Biol Int ; 48(10): 1395-1405, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39010637

RESUMEN

Microproteins, known as micropeptides, are small protein molecules encoded by short open reading frames. These recently identified molecules have been proven to be an essential part of the human proteome that participates in multiple processes, such as DNA repair, mitochondrial respiration, and regulating different signaling pathways. A growing body of studies has evidenced that microproteins exhibit dysregulated expression levels in various malignancies and contribute to tumor progression. It has been reported that microproteins interact with many proteins, such as enzymes (e.g., adenosine triphosphate synthase) and signal transducers (e.g., c-Jun), and regulate malignant cell metabolism, proliferation, and metastasis. Moreover, microproteins have been found to play a significant role in multidrug resistance in vitro and in vivo by their activity in DNA repair pathways. Considering that, this review intended to summarize the roles of microproteins in different aspects of tumorigenesis with diagnostic and therapeutic perspectives.


Asunto(s)
Progresión de la Enfermedad , Neoplasias , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Carcinogénesis/metabolismo , Carcinogénesis/patología , Animales , Transducción de Señal , Péptidos/metabolismo , Reparación del ADN , Micropéptidos
5.
Neuropediatrics ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39074800

RESUMEN

BACKGROUND: Supratentorial intraventricular tumors, encompassing lateral and third ventricular tumors, are uncommon intracranial neoplasms, typically slow-growing and benign, manifesting symptoms only upon reaching a substantial size. This study aims to identify optimal surgical approaches, assess the prevalence and characteristics of these tumors, and evaluate postoperative outcomes among pediatric and adult age groups. METHODS: A retrospective comparative study at a tertiary care hospital from January 2014 to June 2020 included 165 patients (68 pediatrics, 97 adults) meeting inclusion criteria for intraventricular tumor management. Data covered demographic factors, clinical history, neurological assessments, neuroimaging, surgical approaches, histopathological diagnoses, immunohistochemical features, adjuvant therapies, follow-up status, postoperative complications, and morbidity/mortality. RESULTS: Ventricular tumor incidence showed male preponderance in both adults (M:F = 1.2:1) and pediatrics (M:F = 3:1). Lateral ventricles were the most common location. Pediatric cases exhibited more frequent calcifications on computed tomography scans (35.6% vs. 29.5%). Grade II and III tumors were more prevalent in adults within the lateral ventricle (27.1 and 1.9%) compared with pediatrics (6.5 and 8.4%). The third ventricle predominantly featured benign lesions, with pediatric patients experiencing significantly longer hospital stays (16.12 ± 21.94 days vs. 9.58 ± 6.21 days) (p = 0.006). Adults and pediatric patients showed a significant difference in high-grade lateral ventricle tumors (p-value = 0.002*). CONCLUSIONS: Supratentorial ventricular tumors are relatively more prevalent in children than adults, presenting challenges due to size and bleeding risks. Surgical resection is the primary treatment, with a focus on the optimal approach for gross total excision to reduce recurrence risk.

6.
Neuroradiology ; 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060800

RESUMEN

PURPOSE: This study evaluates the efficacy of SISCOS (Subtraction ictal-interictal SPECT coregistered to SPECT) in localizing the epileptogenic zone (EZ) in focal cortical dysplasia (FCD), comparing its predictive performance with MRI and post-surgical outcomes based on ILAE classification. METHODS: 84 patients with drug refractory epilepsy (DRE) who were operated and had histopathology consistent with FCD, were included in the study. All patients had undergone a complete work-up including SISCOS and MRI for EZ localization, followed by discussion in the multidisciplinary epilepsy surgery meeting prior to surgery. Ictal & interictal perfusion SPECT studies were performed with Tc-99 m Ethylene Cysteinate Dimer (Tc-99 m ECD) followed by SISCOS analysis using SPM2 and Bioimage Suite 2.6. Concordance for localization was determined by comparing with the surgical resection site and post-surgical outcomes were assessed using the ILAE classification. RESULTS: The concordance for EZ localization demonstrated by SISCOS was 73.8% and MRI was 82.1%. 52 patients (61.9%) had good surgical outcome and 31(59%) of these were FCD type 2. In patients with discordant MRI findings, SISCOS was able to provide localisation in 86% (13/15), with 69.2% showing good surgical outcomes. Sensitivity of SISCOS and MRI was 73% (95% CI = 59-84.8%) and 78% (95% CI = 67.5-90.3%) respectively with no significant difference between the two. In FCD type I, both SISCOS and MRI revealed a similar a sensitivity of 76.4% (95%CI = 50.1-93.2%). Concordant cases exhibited higher seizure-free odds ratios for both modalities. CONCLUSION: SISCOS is effective in localizing the EZ in FCD patients, comparable to MRI. Integrating SISCOS and MRI enhances lesion detection, especially in MRI discordant cases. A comprehensive diagnostic approach utilizing SISCOS and MRI can optimize the non-invasive pre-surgical assessment in DRE thereby guiding surgical decision-making in a resource-limited setting.

7.
Childs Nerv Syst ; 40(3): 919-924, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37930424

RESUMEN

A 13-year-old female patient presented with painless vision loss and proptosis for 18 months. Imaging findings were highly suggestive of a supraorbital aneurysmal bone cyst (ABC) for which she underwent complete surgical excision. Postoperatively, she developed left hemiparesis. Computed tomography angiography (CTA) revealed right complete internal carotid arterial (ICA) thrombosis. This was managed conservatively, and she improved in hemiparesis over the next 3 weeks. Histopathology report revealed osteosarcoma with secondary ABC, for which she was referred for radiotherapy. At 1.5 months follow-up, the patient's left lower limb power improved to 4 + /5. She was walking without support, and her left upper limb power was 4/5.


Asunto(s)
Quistes Óseos Aneurismáticos , Neoplasias Óseas , Osteosarcoma , Adolescente , Femenino , Humanos , Quistes Óseos Aneurismáticos/complicaciones , Quistes Óseos Aneurismáticos/diagnóstico por imagen , Quistes Óseos Aneurismáticos/cirugía , Neoplasias Óseas/complicaciones , Angiografía por Tomografía Computarizada , Paresia
8.
Childs Nerv Syst ; 40(9): 2723-2733, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38762839

RESUMEN

BACKGROUND: Intracranial mesenchymal chondrosarcoma (IMC) is a rare malignant tumor in pediatric population. IMC can present as extra- or intra-axial lesion in pediatric patients, though the former is commoner causing raised intracranial pressure (ICP). Radiological diagnosis is a challenge in these cases, as is it difficult to differentiate these from other extra-axial neoplasms due to the wide differential diagnosis in pediatric population. We aim to systematically review the literature and present a rare case of extraskeletal intracranial mesenchymal chondrosarcoma treated with safe maximal resection. METHODS: A systematic review of literature was conducted in accordance with PRISMA guidelines. PubMed and Scopus databases were queried using the search terms, "primary intracranial chondrosarcoma", "extraskeletal mesenchymal chondrosarcoma", "mesenchymal chondrosarcoma" and "pediatric". Presentation, surgical management and outcome of a 15-year-old male with an extraskeletal IMC are also described. RESULTS: The search yielded 25 articles which met the inclusion criteria. These published records consisted of 33 IMC cases with mean age at presentation of 9.81 ± 5.2 years (range 2 months to 18 years). Frontal region was the commonest locations (11, 33.3%). Most common presentation was headache (14, 42.4%). All patients underwent surgical intervention: gross total resection (20, 60.6%), subtotal resection (9, 27.3%) and no extent mentioned (4, 12.1%). No adjuvant therapy was received in 15 patients (45.5%). On latest follow-up, 11 patients (33.3%) are on remission, 5 patients (15.2%) are symptom free, 3 patients (9.1%) had recurrence, 2 patients (6.1%) had metastasis and 9 patients (27.3%) expired. CONCLUSION: IMC is a rare entity in pediatric population with imaging findings which are non-characteristic leading to its diagnostic challenge. It can masquerade as other extra-axial intracranial neoplasm (meningioma or hemangiopericytoma). Combination of clinico-radiological and pathological examination can help in accurate diagnosis.  Safe Maximal resection followed by radiotherapy is the preferred treatment strategy.


Asunto(s)
Neoplasias Encefálicas , Condrosarcoma Mesenquimal , Humanos , Condrosarcoma Mesenquimal/cirugía , Condrosarcoma Mesenquimal/diagnóstico por imagen , Condrosarcoma Mesenquimal/patología , Niño , Adolescente , Masculino , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Lactante , Preescolar
9.
Pract Neurol ; 24(4): 313-315, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38423753

RESUMEN

A 25-year-old woman presented with 1 year of progressive orthopnoea, initially explained as bilateral diaphragmatic paresis caused by seronegative myasthenia gravis. She required assisted ventilation and received pyridostigmine and corticosteroids. She had minimal (particularly proximal) symmetrical tetraparesis with apparent bilateral diaphragmatic weakness, but had normal sensation. Further investigation suggested an overlap myositis with shrinking lung syndrome from systemic lupus erythematosus. She improved following immunosuppression with pulse corticosteroids and rituximab, and at 3 months no longer needed bilevel positive airway pressure support.


Asunto(s)
Lupus Eritematoso Sistémico , Parálisis Respiratoria , Humanos , Femenino , Adulto , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Parálisis Respiratoria/etiología , Parálisis Respiratoria/diagnóstico , Diagnóstico Diferencial , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/diagnóstico
10.
Kathmandu Univ Med J (KUMJ) ; 22(86): 241-244, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39328120

RESUMEN

Acute haemorrhagic pancreatitis is a medical emergency and the most severe form of Acute Pancreatitis. It is characterized by severe epigastric pain that radiates to the back and is associated with vomiting. If not diagnosed and managed promptly, it may result in sudden, unexpected, unexplained deaths which fall within the medicolegal domain. In such cases, the role of an autopsy is of paramount importance to determine the cause of death. Here we report a young adult, who presented to the local hospital with vague abdominal discomfort and vomiting following alcohol intake and referred to our tertiary care center for further management. But he was received dead on arrival at our hospital. The diagnosis of acute haemorrhagic pancreatitis was made only after the post mortem examination. Awareness of the physicians about the unusual symptoms in acute haemorrhagic pancreatitis and the need for pancreas examination at autopsy of all sudden deaths is emphasised.


Asunto(s)
Pancreatitis , Humanos , Masculino , Resultado Fatal , Pancreatitis/diagnóstico , Adulto , Autopsia , Enfermedad Aguda , Adulto Joven , Hemorragia/diagnóstico , Hemorragia/etiología
11.
Br J Psychiatry ; 222(6): 241-245, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36994656

RESUMEN

BACKGROUND: Although clozapine is the most efficacious medication for treatment-refractory schizophrenia, not all patients will have an adequate response. Optimising clozapine dose using therapeutic drug monitoring could therefore maximise response. AIMS: Using individual patient data, we undertook a receiver operating characteristic (ROC) curve analysis to determine an optimal therapeutic range for clozapine levels to guide clinical practice. METHOD: We conducted a systematic review of PubMed, PsycINFO and Embase for studies that provided individual participant level data on clozapine levels and response. These data were analysed using ROC curves to determine the prediction performance of plasma clozapine levels for treatment response. RESULTS: We included data on 294 individual participants from nine studies. ROC analysis yielded an area under the curve of 0.612. The clozapine level at the point of optimal diagnostic benefit was 372 ng/mL; at this level, the response sensitivity was 57.3%, and specificity 65.7%. The interquartile range for treatment response was 223-558 ng/mL. There was no improvement in ROC performance with mixed models including patient gender, age or length of trial. Clozapine dose and clozapine concentration to dose ratio did not provide significantly meaningful prediction of response to clozapine. CONCLUSIONS: Clozapine dose should be optimised based on clozapine therapeutic levels. We found that a range between 250 and 550 ng/mL could be recommended, while noting that a level of >350 ng/mL is the most optimal for response. Although some patients may not respond without clozapine levels >550 ng/mL, the benefits should be weighed against the increased risk of adverse drug reactions.


Asunto(s)
Antipsicóticos , Clozapina , Esquizofrenia , Humanos , Clozapina/uso terapéutico , Antipsicóticos/uso terapéutico , Curva ROC , Esquizofrenia/diagnóstico , Escalas de Valoración Psiquiátrica
12.
Childs Nerv Syst ; 39(12): 3607-3612, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37300577

RESUMEN

INTRODUCTION: Intracranial myeloid sarcoma is a rare extramedullary presentation of acute myeloid leukemia (AML). It can involve the meninges and ependyma presenting as extra-axial mass lesion. Rarely, it can also invade the brain parenchyma. It is commonly seen in children. It is usually misdiagnosed due to its close resemblance to other intracranial tumors (meningioma, metastasis, Ewing's sarcomas, and lymphoma). These are underdiagnosed if they precede the diagnosis of leukemia. CASE REPORT: A 7-year-old boy with isolated intracranial myeloid sarcoma who presented with raised intracranial pressure (ICP) which was successfully managed by surgical excision. CONCLUSION: Isolated intracranial myeloid sarcoma is a rare presentation of AML. Leukemia can be diagnosed early during the postoperative period and can be started on therapy timely. These patients requires regular follow-ups (clinical, laboratory and radiological) to detect relapses early.


Asunto(s)
Neoplasias Encefálicas , Leucemia Mieloide Aguda , Neoplasias Meníngeas , Sarcoma de Ewing , Sarcoma Mieloide , Masculino , Niño , Humanos , Sarcoma Mieloide/diagnóstico por imagen , Sarcoma Mieloide/cirugía , Leucemia Mieloide Aguda/diagnóstico por imagen , Leucemia Mieloide Aguda/patología , Neoplasias Meníngeas/diagnóstico , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía
13.
J Postgrad Med ; 69(4): 234-236, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37530377

RESUMEN

Mesenteric vascular thrombosis, typically of the superior mesenteric artery, is a frequent occurrence in patients with hypercoagulable conditions. Isolated involvement of the celiac artery is rare. Patients with celiac artery thrombosis can present with an acute abdomen or occasionally with acid peptic symptoms. A delay in diagnosis is associated with high rates of morbidity and mortality. We present a rare case of splenic infarction with celiac trunk thrombosis in a 54-year-old patient with underlying antiphospholipid (APLA) syndrome who presented with epigastric pain that was mistaken for symptoms of acid reflux.


Asunto(s)
Abdomen Agudo , Trombosis , Humanos , Persona de Mediana Edad , Arteria Celíaca/diagnóstico por imagen , Abdomen Agudo/etiología , Arteria Mesentérica Superior/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Dolor Abdominal/etiología
14.
J Indian Assoc Pediatr Surg ; 28(6): 465-471, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38173635

RESUMEN

Aims: The aim of this study was to compare the immediate and long-term outcomes after high spermatic vessel ligation (HSVL) and low spermatic vessel ligation (LSVL) in a high undescended testis (UDT) model in rats. Materials and Methods: A prospective randomized controlled study was conducted on 24 male Wistar rats. The rats were randomly divided into three groups. Group A underwent a sham laparotomy and acted as the control. Group B underwent HSVL of both testicular vessels. Group C underwent LSVL of both testicular vessels. Each group was again subdivided into two subgroups. One sub-group underwent blood collection and testicular biopsy of both testes 24 h after the procedure to demonstrate immediate changes. Other subgroups underwent blood sample collection and testicular biopsy of both testes on day 50 following the procedure for hormonal changes and long-term changes. Results: All the testes in HSVL showed atrophy (100%) in the long term, whereas LSVL showed atrophy in 12.5% of testes, even though both groups showed adequate neovascularization. Testes in HSVL showed poor bleeding on incision at both 24 h and day 50. On histology, 75% of testes in HSVL showed complete necrosis, and 50% in LSVL showed partial necrosis at 24 h. On day 50, all the testes in HSVL (100%) showed complete necrosis with dystrophic calcification, whereas all the testes in LSVL showed normal histology with good maturation of seminiferous tubules. There was no significant difference in testosterone levels between both groups. Conclusions: Both immediate and long-term changes following LSVL showed an increase in blood flow to the testis after ligation through collaterals and reverses early ischemic changes to the testis. Given the higher testicular atrophic rate after HSVL, LSVL or at least low ligation can be preferred for the management of high intra-abdominal UDT.

15.
Kathmandu Univ Med J (KUMJ) ; 21(84): 399-403, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-39212015

RESUMEN

Background Traumatic brain injury (TBI) is a significant cause of disability and mortality globally. Information regarding clinical presentation and management of TBI patients in the district hospital settings is inadequate, especially in low- and middle-income countries. Objective This study aims to describe the demographic and clinical profiles of traumatic brain injury patients in a district hospital setting in Nepal. Method This study was done at Chautara Hospital in Sindhupalchowk district from December 2021 to June 2022. Sixty-one patients were included using non-probability sampling. The age and sex of patients, cause of injury, distance from the hospital, the severity of the injury based on the Glasgow Coma Scale, site of trauma on the head, and disposition of patients were analyzed. Result Sixty-one patients met the inclusion criteria out of which 29 were males and 32 were females. The mean age of the patients was 42.5 years. The most frequent cause was fall from height (23), and the most common injury site was the frontal region of the head (29). Most patients had a mild injury (52) followed by severe (five). Only two patients had moderate injury. Forty-two patients sustained injury within 5 kilometres of the hospital. Thirty patients were referred to higher centres for further treatment. Conclusion Falls from height is the most common cause of traumatic brain injury followed by road traffic accidents. As most of the cases are mild in severity, the availability of trained human resources and telemedicine consultation in district hospitals can substantially decrease referral to higher centres and therefore decrease the burden of traumatic brain injury patients in the higher centres.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Escala de Coma de Glasgow , Hospitales de Distrito , Humanos , Nepal/epidemiología , Masculino , Lesiones Traumáticas del Encéfalo/epidemiología , Lesiones Traumáticas del Encéfalo/terapia , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Adolescente , Anciano , Accidentes por Caídas/estadística & datos numéricos
16.
Kathmandu Univ Med J (KUMJ) ; 21(83): 325-330, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-39206655

RESUMEN

Background The basic principles of research methodology are very important for the successful conduct of research. Objective To evaluate the knowledge and perceptions before and after a three-day workshop on health research methodologies conducted at a medical college in Lalitpur, Nepal. Method The pre-post study was conducted during the workshop. There were 31 participants comprising of doctors (interns and residents), medical officers and dental surgeons and faculties. A questionnaire containing two sections related to various themes of the workshop was developed to measure the respondents' knowledge and perception of different concepts. Feedback regarding each session was also obtained. The median knowledge and perception scores before and after the workshop were compared using appropriate statistical tests (p < 0.05). Result More than half of the participants, [18 (58.1%)] were of 20-30 years of age. The total knowledge scores improved significantly after the workshop. The increase in the perception scores after the workshop was also significant. Feedback was positive. The highest feedback score was for the session on critical analysis of a published article. Conclusion Knowledge and perceptions increased significantly indicating such workshops can be effective and contribute to the capacity building of the early-stage researchers.


Asunto(s)
Investigación Biomédica , Humanos , Nepal , Adulto , Masculino , Femenino , Encuestas y Cuestionarios , Adulto Joven , Conocimientos, Actitudes y Práctica en Salud
17.
Cell Mol Neurobiol ; 42(4): 1049-1064, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-33258018

RESUMEN

Histone deacetylases (HDACs) have been described to have both neurotoxic and neuroprotective roles, and partly, depend on its sub-cellular distribution. HDAC inhibitors have a long history of use in the treatment of various neurological disorders including epilepsy. Key role of HDACs in GABAergic neurotransmission, synaptogenesis, synaptic plasticity and memory formation was demonstrated whereas very less is known about their role in drug-resistant epilepsy pathologies. The present study was aimed to investigate the changes in the expression of HDACs, activity and its sub-cellular distribution in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) patients. For this study, surgically resected hippocampal tissue specimens of 28 MTLE-HS patients and 20 hippocampus from post-mortem cases were obtained. Real-time PCR was done to analyse the mRNA expression. HDAC activity and the protein levels of HDACs in cytoplasm as well as nucleus were measured spectrophotometrically. Further, sub-cellular localization of HDACs was characterized by immunofluorescence. Significant upregulation of HDAC1, HDAC2, HDAC4, HDAC5, HDAC6, HDAC10 and HDAC11 mRNA were observed in MTLE-HS. Alterations in the mRNA expression of glutamate and gamma-aminobutyric acid (GABA) receptor subunits have been also demonstrated. We observed significant increase of HDAC activity and nuclear level of HDAC1, HDAC2, HDAC5 and HDAC11 in the hippocampal samples obtained from patients with MTLE-HS. Moreover, we found altered cytoplasmic level of HDAC4, HDAC6 and HDAC10 in the hippocampal sample obtained from patients with MTLE-HS. Alterations in the level of HDACs could potentially be part of a dynamic transcription regulation associated with MTLE-HS. Changes in cytoplasmic level of HDAC4, 6 and 10 suggest that cytoplasmic substrates may play a crucial role in the pathophysiology of MTLE-HS. Knowledge regarding expression pattern and sub-cellular distribution of HDACs may help to devise specific HDACi therapy for epilepsy.


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Epilepsia/patología , Epilepsia del Lóbulo Temporal/metabolismo , Hipocampo/metabolismo , Histona Desacetilasas/metabolismo , Humanos , Imagen por Resonancia Magnética , Esclerosis/patología
18.
J Endocrinol Invest ; 45(2): 337-346, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34302683

RESUMEN

PURPOSE: Calcium sensing receptor (CaSR), on the surface of normal parathyroid cells, is essential for maintaining serum calcium levels. The normal pattern of CaSR immunostaining remains undefined and is presumptively circumferential. Given the physiological variation in serum calcium, we postulated that CaSR expression could not be uniformly circumferential. Also, cytoplasmic expression has not been evaluated either in normal or pathological tissues. We studied normal parathyroid tissues derived from forensic autopsies and those rimming parathyroid adenomas for membranous and cytoplasmic CaSR immunoexpression. Results were compared with primary hyperparathyroidism (PHPT) to look for any pathogenetic implications. MATERIALS AND METHODS: We evaluated 34 normal parathyroid tissues from 11 autopsies, 30 normal rims, 45 parathyroid adenoma, 10 hyperplasia, and 7 carcinoma cases. Membranous expression was categorized complete/incomplete and weak/moderate/strong; scored using Her2/Neu and Histo-scores; predominant pattern noted. Cytoplasmic expression was categorized negative/weak/moderate/strong; predominant intensity noted. RESULTS: Normal autopsy-derived parathyroid tissues were Her2/Neu 3 + , but incomplete membranous staining predominated in 85%. Their immune-scores were significantly more than the cases (p < < 0.05). The mean histo-score of normal rims was intermediate between the two (p < < 0.05). Cytoplasmic expression was strong in all autopsy-derived tissues, weak/negative in hyperplasia (100%), moderate in 16% adenomas, and 43% carcinomas. CONCLUSIONS: Normal autopsy-derived parathyroid tissues showed strong but predominantly incomplete membranous expression. Surface CaSR expression decreased in PHPT and is probably an early event in parathyroid adenoma, seen even in normal rims. Whether there is a defect in CaSR trafficking from the cytoplasm to the cell surface in adenoma and carcinoma needs further evaluation.


Asunto(s)
Hiperparatiroidismo Primario , Glándulas Paratiroides , Neoplasias de las Paratiroides , Receptores Sensibles al Calcio/análisis , Adulto , Autopsia , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Hiperparatiroidismo Primario/metabolismo , Hiperparatiroidismo Primario/patología , Inmunohistoquímica , Técnicas Inmunológicas/métodos , Proteínas Sensoras del Calcio Intracelular/metabolismo , Masculino , Glándulas Paratiroides/metabolismo , Glándulas Paratiroides/patología , Neoplasias de las Paratiroides/metabolismo , Neoplasias de las Paratiroides/patología
19.
J Postgrad Med ; 68(2): 109-111, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35466663

RESUMEN

Hypoglycemia presents with a spectrum of neurological manifestations ranging from lightheadedness to confusion and coma. We report here the case of a 61-year-old woman with right hemiparesis presenting within the window period for stroke thrombolysis. MRI brain showed diffusion restriction in posterior limb of left internal capsule and splenium. Patient had documented hypoglycemia of 38 mg/dL. Patient's hemiparesis resolved after glucose correction, and radiological findings completely resolved after 10 days. We present this case to highlight the rare radiological finding of simultaneous internal capsule and splenium involvement in hypoglycemic hemiparesis and the importance to rule out stroke mimics to avoid unwanted thrombolysis.


Asunto(s)
Hipoglucemia , Accidente Cerebrovascular , Cuerpo Calloso/patología , Femenino , Humanos , Hipoglucemia/etiología , Hipoglucemia/patología , Hipoglucemiantes , Cápsula Interna/diagnóstico por imagen , Imagen por Resonancia Magnética , Persona de Mediana Edad , Paresia/etiología , Paresia/patología , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/patología
20.
J Postgrad Med ; 68(2): 85-92, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35466661

RESUMEN

Aims: No Cochrane meta-analysis with grading of evidence is available on use of hydroxychloroquine (HCQ) in type-2 diabetes (T2DM). This meta-analysis evaluated the efficacy and safety of HCQ in T2DM. Methods: Electronic databases were searched using a Boolean search strategy: ((hydroxychloroquine) OR (chloroquine*)) AND ((diabetes) OR ("diabetes mellitus") OR (glycemia) OR (glucose) OR (insulin)) for studies evaluating hydroxychloroquine for glycemic control in T2DM. The primary outcome was a change in glycated haemoglobin (HbA1c). The secondary outcomes were changes in other glycemic/lipid parameters and adverse effects. Results: Data from 11 randomized controlled trials (RCTs) (3 having placebo as controls [passive controls] and 8 having anti-diabetes medications as controls [active controls]) involving 2,723 patients having a median follow-up of 24 weeks were analyzed. About 54.54% of the RCTs were of poor quality as evaluated by the Jadad scale. The performance bias and detection bias were at high risk in 63.64% of the RCTs. The HbA1c reduction with HCQ was marginally better compared to the active (mean differences [MD]-0.17% [95%, CI:-0.30--0.04;P=0.009;I2=89%; very low certainty of evidence, VLCE]), and passive (MD-1.35% [95%CI:-2.10--0.59;P=0.005;I2=74%]) controls. A reduction in fasting glucose (MD-16.63mg/dL[95%, CI: -25.99 - -7.28mg/dL;P<0.001;I2=97%;VLCE]) and post-prandial glucose [MD -8.41mg/dL (95%CI: -14.71 - -2.12mg/dL;P=0.009;I2=87%;VLCE]), appeared better with HCQ compared to active controls. The total adverse events (risk ratio [RR]0.93 [95% CI:0.68-1.28]; P=0.65;I2=66%) were not different with HCQ compared to the controls. Conclusion: The routine use of HCQ in T2DM cannot be recommended based on the current evidence.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hidroxicloroquina , Glucemia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada , Humanos , Hidroxicloroquina/efectos adversos
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