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1.
Prim Care ; 51(2): 211-232, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692771

RESUMO

Seizures and epilepsy are common neurologic conditions that are frequently encountered in the outpatient primary care setting. An accurate diagnosis relies on a thorough clinical history and evaluation. Understanding seizure semiology and classification is crucial in conducting the initial assessment. Knowledge of common seizure triggers and provoking factors can further guide diagnostic testing and initial management. The pharmacodynamic characteristics and side effect profiles of anti-seizure medications are important considerations when deciding treatment and counseling patients, particularly those with comorbidities and in special populations such as patient of childbearing potential.


Assuntos
Anticonvulsivantes , Epilepsia , Atenção Primária à Saúde , Convulsões , Humanos , Epilepsia/diagnóstico , Epilepsia/terapia , Convulsões/diagnóstico , Convulsões/terapia , Anticonvulsivantes/uso terapêutico , Médicos de Atenção Primária , Feminino , Anamnese
2.
Acta Neurol Belg ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589733

RESUMO

Cefepime is a fourth-generation cephalosporin that is widely used to treat sepsis but is associated with a potentially dangerous neurotoxicity syndrome, cefepime-induced neurotoxicity (CIN). As a result, patients treated with cefepime may be at higher risk for morbidity, including seizures, and mortality. Though the recent ACORN trial concluded that cefepime does not increase the risk of mortality, most of these patients were not critically ill or elderly, two of the most at risk populations for CIN. Further, diagnosis may be difficult in the critical care setting as patients may have multiple reasons for encephalopathy. Therefore, this population in particular should be studied and monitored closely for CIN. Importantly, there are not well defined diagnostic criteria for CIN to guide evaluation and management. Defining the risk factors for CIN and using laboratory and EEG to help support the clinical diagnosis could be helpful in early recognition of CIN to help institute treatment and to rule out seizures. In this mini review, we highlight risk factors for CIN, discuss the possible value of EEG, and propose a diagnostic and management approach in the evaluation and management of CIN.

3.
Nat Commun ; 15(1): 1870, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467607

RESUMO

Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis, however, its efficiency declines with age. Regulatory T cells (Treg) recently emerged as critical players in tissue regeneration, including remyelination. However, the effect of ageing on Treg-mediated regenerative processes is poorly understood. Here, we show that expansion of aged Treg does not rescue age-associated remyelination impairment due to an intrinsically diminished capacity of aged Treg to promote oligodendrocyte differentiation and myelination in male and female mice. This decline in regenerative Treg functions can be rescued by a young environment. We identified Melanoma Cell Adhesion Molecule 1 (MCAM1) and Integrin alpha 2 (ITGA2) as candidates of Treg-mediated oligodendrocyte differentiation that decrease with age. Our findings demonstrate that ageing limits the neuroregenerative capacity of Treg, likely limiting their remyelinating therapeutic potential in aged patients, and describe two mechanisms implicated in Treg-driven remyelination that may be targetable to overcome this limitation.


Assuntos
Remielinização , Humanos , Masculino , Feminino , Camundongos , Animais , Idoso , Remielinização/fisiologia , Linfócitos T Reguladores/metabolismo , Oligodendroglia/fisiologia , Diferenciação Celular/fisiologia , Bainha de Mielina/metabolismo , Envelhecimento , Sistema Nervoso Central
4.
J Clin Neurophysiol ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38194635

RESUMO

PURPOSE: To evaluate the clinical and electrographic characteristics of critically ill pediatric patients with lateralized rhythmic delta activity (LRDA) and compare them with patients with lateralized periodic discharges (LPDs). METHODS: This was a retrospective study examining consecutive critically ill pediatric patients (1 month-18 years) with LRDA or LPDs monitored on continuous electroencephalography. Clinical, radiologic, and electrographic characteristics; disease severity; and acute sequelae were compared between the two groups. RESULTS: Of 668 pediatric patients monitored on continuous electroencephalography during the study period, 12 (1.79%) patients had LRDA and 15 (2.24%) had LPDs. The underlying etiologies were heterogeneous with no difference in the acuity of brain MRI changes between both groups. Lateralized rhythmic delta activity and LPDs were concordant with the side of MRI abnormality in most patients [85.7% (LRDA) and 83.3% (LPD)]. There was no difference in the measures of disease severity between both groups. Seizures were frequent in both groups (42% in the LRDA group and 73% in the LPD group). Patients in the LPD group had a trend toward requiring a greater number of antiseizure medications for seizure control (median of 4 vs. 2 in the LRDA group, p = 0.09), particularly those patients with LPDs qualifying as ictal-interictal continuum compared with those without ictal-interictal continuum (p = 0.02). CONCLUSIONS: Lateralized rhythmic delta activity and LPDs are uncommon EEG findings in the pediatric population. Seizures occur commonly in patients with these patterns. Seizures in patients with LPDs, especially those qualifying as ictal-interictal continuum, showed a trend toward being more refractory. Larger studies are needed in the future to further evaluate these findings.

5.
J Pharmacol Exp Ther ; 388(1): 12-22, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-37699708

RESUMO

Proteinase-activated receptor-2 (PAR2), which modulates inflammatory responses, is elevated in the central nervous system in multiple sclerosis (MS) and in its murine model, experimental autoimmune encephalomyelitis (EAE). In PAR2-null mice, disease severity of EAE is markedly diminished. We therefore tested whether inhibiting PAR2 activation in vivo might be a viable strategy for the treatment of MS. Using the EAE model, we show that a PAR2 antagonist, the pepducin palmitoyl-RSSAMDENSEKKRKSAIK-amide (P2pal-18S), attenuates EAE progression by affecting immune cell function. P2pal-18S treatment markedly diminishes disease severity and reduces demyelination, as well as the infiltration of T-cells and macrophages into the central nervous system. Moreover, P2pal-18S decreases granulocyte-macrophage colony-stimulating factor (GM-CSF) production and T-cell activation in cultured splenocytes and prevents macrophage polarization in vitro. We conclude that PAR2 plays a key role in regulating neuroinflammation in EAE and that PAR2 antagonists represent promising therapeutic agents for treating MS and other neuroinflammatory diseases. SIGNIFICANCE STATEMENT: Proteinase-activated receptor-2 modulates inflammatory responses and is increased in multiple sclerosis lesions. We show that the proteinase-activated receptor-2 antagonist palmitoyl-RSSAMDENSEKKRKSAIK-amide reduces disease in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis by inhibiting T-cell and macrophage activation and infiltration into the central nervous system, making it a potential treatment for multiple sclerosis.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Camundongos , Animais , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/patologia , Doenças Neuroinflamatórias , Receptor PAR-2 , Esclerose Múltipla/tratamento farmacológico , Camundongos Knockout , Amidas/uso terapêutico , Camundongos Endogâmicos C57BL
6.
Int J Gynaecol Obstet ; 165(1): 107-116, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37724021

RESUMO

INTRODUCTION: The use of oral azithromycin (AZI) as a preventive measure against postpartum infections of planned vaginal births has garnered a lot of interest in recent years and has been the subject of many randomized controlled trials (RCTs). However, the results from these trials have not been consistent. Therefore, we aim to perform a systematic review and meta-analysis to determine whether the use of a single-dose of oral AZI is clinically significant. METHODS: We systematically searched PubMed, Embase, and Cochrane Central for RCTs from May to June 2023, comparing a single dose of oral AZI with placebo in patients undergoing planned vaginal delivery at a minimum of 28 weeks of gestational age. The main outcomes were puerperal and neonatal sepsis. Statistical analyses were performed using Review Manager 5.4.1 (Cochrane Collaboration). Heterogeneity was assessed with I2 statistics. RESULTS: Four RCTs were included (mothers, n = 42 235; newborns n = 42 492). Approximately 49.8% of mothers received a single dose of oral AZI for sepsis prophylaxis. Compared with placebo, AZI significantly reduced the incidence of puerperal sepsis (risk ratio [RR], 0.65 [95% confidence interval (CI), 0.55-0.77]; P < 0.001), mastitis or breast abscess (RR, 0.58 [95% CI, 0.42-0.79]; P < 0.001), endometritis (RR, 0.65 [95% CI, 0.54-0.77]; P < 0.001), wound infection (RR, 0.81 [95% CI, 0.69-0.96]; P = 0.013), infection rate (RR, 0.62 [95% CI, 0.51-0.76]; P < 0.001), and fever (RR, 0.50 [95% CI, 0.28-0.89]; P = 0.018) in mothers. No statistically significant differences were identified between groups regarding maternal all-cause mortality and the use of prescribed postpartum antibiotics. Similarly, no statistical differences were noted in the neonatal group regarding sepsis, infection rate, and all-cause mortality. CONCLUSION: AZI appears to be an effective preventive measure against many postpartum infections in mothers but a substantial impact on neonatal outcomes has not yet been conclusively observed.


Assuntos
Azitromicina , Sepse , Gravidez , Feminino , Recém-Nascido , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Antibacterianos/uso terapêutico , Parto Obstétrico , Sepse/prevenção & controle
7.
Eur Rev Med Pharmacol Sci ; 27(23): 11421-11432, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38095390

RESUMO

OBJECTIVE: This study aims to identify the characteristics of Egyptian patients suffering from type 2 diabetes mellitus (T2DM), determine disease control rates, and gain insights into clinical treatments. PATIENTS AND METHODS: A total of 2,516 patients with T2DM were recruited from 244 private clinics across Egypt in a one-month period from May to June 2017. Data collected from patients included glycemic control parameters of glycosylated hemoglobin, fasting plasma glucose, and postprandial glucose. Additional information gathered included patients' weight, age, level of physical activity, smoking habits, presence of comorbidities, type of treatment received for type 2 diabetes, number and severity of hypoglycemic events, as well as treatment modification by the physician in the last visit. The type of statistics used for the analysis is descriptive statistics and regression model. RESULTS: Only 18.4% of participating patients achieved the target level of glycosylated hemoglobin of 7% or below. The mean age of these patients was 54±11.2 years, and the mean duration since the first diagnosis was 6.6±6.4 years. A total of 33.4% of all patients had no known comorbidity, while the rest had one or more known and treated comorbidities. A total of 76% of patients received sulfonylurea either as monotherapy or in combination with other treatments. In addition, no treatment modifications or adjustments were provided for 32% of the study participants who did not reach their glycemic control target. CONCLUSIONS: In Egypt, there is a low rate of glycemic control among private patients and a high prevalence of comorbid conditions. This is likely to cause a significant health burden to people with T2DM, the healthcare system, and the economy due to a loss in productivity. This study presented an argument for better-managed measures to improve glycemic control in the population, such as patient education to increase patient awareness and adherence to treatment protocols as well as improved adherence to guidelines by clinicians.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Egito/epidemiologia , Hemoglobinas Glicadas , Glicemia , Hipoglicemiantes
8.
Hepat Med ; 15: 233-247, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38146425

RESUMO

Background: This study describes the epidemiological pattern of acute hepatitis B virus (HBV) infection in Saudi Arabia from 2006 to 2021. It explores case frequency and the crude incidence rate (CIR) by year of diagnosis, age group, region, gender, and nationality of patients. Methods: Retrospective data on acute hepatitis B cases diagnosed across 20 regions of Saudi Arabia during January 2006 to December 2021 were obtained from the Saudi Ministry of Health's Statistical Yearbook. Statistical analyses were conducted using SPSS version 20.0, employing both parametric and non-parametric tests. Results: The highest CIR was reported in the regions of Qunfudah, Jeddah, Tabuk, and Taif (28.6, 25.2, 25.1, and 23.4 per 100,000 people). In contrast, the lowest CIR was documented in the regions of Hail, Qurayyat, Jouf, and Hafr AL-Baten (3.6, 3.5, 2.9, and 1.2 per 100,000 people). Incidence rates were notably elevated in those aged 45 years and above (30.6 per 100,000 individuals), followed by the 15-44 age group (14.2 per 100,000 individuals), and were lowest in children aged 0-14 years (0.8 per 100,000 individuals). Regarding gender differences, HBV infection rates were 1.4 times higher in Saudi males than females and 2.2 times higher in non-Saudi males compared to females. Overall, Saudi nationals had a 4.2 times higher HBV infection rate than non-Saudis during the study period. Conclusion: This study highlights diverse acute Hepatitis B infection rates across Saudi regions, with higher rates in Qunfudah, Jeddah, Tabuk, and Taif, and lower rates in Hail, Qurayyat, Jouf, and Hafr AL-Baten. Predominance among ages 45+, followed by 15-44, and lowest in 0-14 age groups was observed. Gender variations showed notably higher rates in Saudi and non-Saudi males. The notably higher prevalence among Saudi nationals implies key considerations for public health strategies.

9.
J Child Neurol ; 38(10-12): 581-589, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37624689

RESUMO

BACKGROUND / OBJECTIVE: Seizures are a complication for pediatric patients requiring extracorporeal membrane oxygenation (ECMO). There are no standardized guidelines regarding continuous electroencephalography (EEG) monitoring to detect seizures in these patients, and the impact of protocolized monitoring has not been evaluated. Here we examined the effects of continuous EEG protocol implementation in our pediatric ECMO population. METHODS: Retrospective chart reviews were conducted on 57 patients who underwent extracorporeal membrane oxygenation and concurrent continuous EEG out of 165 patients supported on extracorporeal membrane oxygenation. Timing of continuous EEG initiation and seizures detected by continuous EEG was determined for 5 years prior to and 15 months after protocol implementation. RESULTS: Protocol implementation was associated with increased ECMO-supported patients who were concurrently monitored by continuous EEG. Time from ECMO cannulation to continuous EEG initiation was shorter (median 7 hours after versus 16.2 hours before; P < .001). Patients who had ongoing seizures at the start of continuous EEG recording decreased from 64% preprotocol to 0% postprotocol (P < .001), and there was an associated earlier time to break in status epilepticus postprotocol. Seizures were detected past 48 hours after cannulation in 50% of patients in the postprotocol group. CONCLUSIONS: Protocol implementation resulted in earlier continuous EEG initiation and more EEGs initiated before seizure onset with evidence of altered seizure dynamics. Although current recommendations suggest that continuous EEG duration of 24-48 hours results in seizure detection for >90% of critically ill adults, longer monitoring may be needed to reliably detect seizures in children supported with ECMO, particularly if monitoring is initiated earlier in the post-cannulation period.


Assuntos
Oxigenação por Membrana Extracorpórea , Estado Epiléptico , Adulto , Criança , Humanos , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/terapia , Convulsões/epidemiologia , Eletroencefalografia/métodos , Estado Epiléptico/etiologia
10.
Eur Rev Med Pharmacol Sci ; 27(12): 5530-5541, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37401289

RESUMO

OBJECTIVE: Acromegaly is a fatal and chronic disease that is caused by the abnormal secretion of growth hormone (GH) by the pituitary adenoma or pituitary tumor, resulting in an increased circulated concentration of insulin-like growth factors 1 (IGF-1), where in most of the cases it is secreted by a pituitary tumor. Higher levels of GH cause an increase in IGF-1 in the liver leading to multiple conditions such as cardiovascular diseases, glucose imbalance, cancer, and sleep apnea. Medical treatments such as surgery and radiotherapy can be used as the first choice of patients; however, specified human growth hormone control should be an essential treatment strategy due to an incidence rate of 0.2-1.1 yearly. Therefore, the main focus of this study is to develop a novel drug for treating acromegaly by exploiting medicinal plants that have been screened using phenol as a pharmacophore model to identify target therapeutic medicinal plant phenols. MATERIALS AND METHODS: The screening identified thirty-four pharmacophore matches of medicinal plant phenols. These were selected as suitable ligands and were docked against the growth hormone receptor to calculate their binding affinity. The candidate with the highest screened score was fragment-optimized and subjected to absorption, distribution, metabolism, and excretion (ADME) analysis, in-depth toxicity predictions, interpretation of Lipinski's rule, and molecular dynamic simulations to check the behavior of the growth hormone with the fragment-optimized candidate. RESULTS: The highest docking energy was calculated as -6.5 K/mol for Bauhiniastatin-1. Enhancing the performance of Bauhiniastatin-1 against the growth hormone receptor with fragment optimization portrayed that human growth hormone inhibition can be executed in a more efficient and better way. Fragment-optimized Bauhiniastatin-1 (FOB) was predicted with high gastrointestinal absorption, a water solubility of -2.61 as soluble, and synthetic accessibility of 4.50, achieving Lipinski's rule of 5, with low organ toxicity prediction and interpreting a positive behavior against the targeted protein. The discovery of a de novo drug candidate was confirmed by the docking of fragment-optimized Bauhiniastatin-1 (FOB), which had an energy of -4,070 Kcal/mol. CONCLUSIONS: Although successful and completely harmless, present healthcare treatment does not always eradicate the disease in some individuals. Therefore, novel formulas or combinations of currently marketed medications and emergent phytochemicals will provide new possibilities for these instances.


Assuntos
Acromegalia , Hormônio do Crescimento Humano , Neoplasias Hipofisárias , Humanos , Acromegalia/tratamento farmacológico , Acromegalia/etiologia , Acromegalia/cirurgia , Fator de Crescimento Insulin-Like I/metabolismo , Farmacóforo , Fenóis/uso terapêutico , Receptores da Somatotropina/uso terapêutico , Hormônio do Crescimento
11.
J Pharm Pharmacol ; 75(9): 1186-1197, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37177978

RESUMO

OBJECTIVES: To compare the therapeutic potential of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) preconditioned ex-vivo with resveratrol (MCR) and BM-MSCs isolated from resveratrol-pre-treated rats (MTR) in type-1 diabetic rats. METHODS: Type-1 diabetes was induced by a single streptozotocin injection (50 mg/kg; ip) in 24 rats. Following the confirmation of T1DM, diabetic rats were randomly divided into four groups: diabetic control (DC), diabetic rats treated with insulin subcutaneous (7.5 IU/kg/day), diabetic rats treated with MCR cells (3 × 106cells/rat, intravenous) and diabetic rats treated with MTR cells (3 × 106cells/rat, intravenous). Rats were sacrificed 4 weeks following cellular transplantation. KEY FINDINGS: Untreated diabetic rats suffered from pancreatic cell damage, had high blood glucose levels, increased apoptotic, fibrosis, and oxidative stress markers and decreased survival and pancreatic regeneration parameters. Both MSCs preconditioned ex-vivo with RES and MSCs isolated from rats pre-treated with RES homed successfully in injured pancreas and showed therapeutic potential in the treatment of STZ-induced T1DM. MCR cells showed better efficiency than MTR cells. CONCLUSIONS: The pre-conditioning of BM-MSCs with resveratrol may be a promising therapeutic possibility in T1DM. Resveratrol-preconditioned BM-MSCs encouraged effects almost comparable to that of exogenous insulin with the advantages of cured pancreas and restored islets not attained by insulin.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Ratos , Animais , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/tratamento farmacológico , Resveratrol/farmacologia , Estreptozocina/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/terapia , Medula Óssea , Insulina/farmacologia
12.
Neurol Clin Pract ; 13(2): e200135, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36936394

RESUMO

Background and Objectives: Case reports and case series have described fluorodeoxyglucose (FDG)-PET findings in critically ill patients with rhythmic or periodic EEG patterns, with one reporting that metabolic activity increases with increasing lateralized periodic discharge (LPD) frequency. However, larger studies examining the relationship between FDG-PET hypermetabolism and rhythmic or periodic EEG patterns are lacking. The goal of this study was to investigate the association of FDG-PET hypermetabolism with electroencephalographic features in patients with neurologic disorders. Methods: This was a single-center, retrospective study of adult patients admitted with acute neurologic symptoms who underwent FDG-PET imaging and EEG monitoring within 24 hours. Subjects were divided into 2 groups based on their FDG-PET metabolism pattern: hypermetabolic activity vs hypometabolic or normal metabolic activity. Chi-square tests and logistic regression were used to determine the relationship of FDG-PET metabolism and EEG findings. Results: Sixty patients met the inclusion criteria and underwent 63 FDG-PET studies and EEGs. Twenty-seven studies (43%) showed hypermetabolism while 36 studies (57%) showed either hypometabolism or no abnormalities on FDG-PET. Subjects with hypermetabolic FDG-PET were more likely to have electrographic seizures (44% vs 8%, p = 0.001) and LPDs with/without seizures (44% vs 14%, p = 0.007), but not other rhythmic or periodic EEG patterns (lateralized rhythmic delta activity, generalized periodic discharges, or generalized rhythmic delta activity). Subjects with hypermetabolism and LPDs were more likely to have concurrent electrographic seizures (58% vs 0%, p = 0.03), fast activity associated with the discharges (67% vs 0, p = 0.01), or spike morphology (67% vs 0, p = 0.03), compared with subjects with hypometabolic FDG-PET and LPDs. Discussion: Adults admitted with acute neurologic symptoms who had hypermetabolic FDG-PET were more likely to show electrographic seizures and LPDs, but not other rhythmic or periodic EEG patterns, compared with those with hypometabolic FDG-PET. Subjects with hypermetabolic FDG-PET and LPDs were more likely to have LPDs with concurrent electrographic seizures, LPDs with a spike morphology, and LPDs +F, compared with subjects with hypometabolic FDG-PET.

13.
Ann N Y Acad Sci ; 1519(1): 34-45, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36398864

RESUMO

Aging is a major risk factor for several neurodegenerative diseases and is associated with cognitive decline. In addition to affecting neuronal function, the aging process significantly affects the functional phenotype of the glial cell compartment, comprising oligodendrocyte lineage cells, astrocytes, and microglia. These changes result in a more inflammatory microenvironment, resulting in a condition that is favorable for neuron and synapse loss. In addition to facilitating neurodegeneration, the aging glial cell population has negative implications for central nervous system remyelination, a regenerative process that is of particular importance to the chronic demyelinating disease multiple sclerosis. This review will discuss the changes that occur with aging in the three main glial populations and provide an overview of the studies documenting the impact these changes have on remyelination.


Assuntos
Doenças Desmielinizantes , Bainha de Mielina , Humanos , Neuroglia , Sistema Nervoso Central/fisiologia , Regeneração Nervosa , Oligodendroglia/fisiologia
14.
Cancer Immunol Immunother ; 72(3): 733-742, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36194288

RESUMO

BACKGROUND: The role of tumor-associated macrophages (TAMs) in glioblastoma (GBM) disease progression has received increasing attention. Recent advances have shown that TAMs can be re-programmed to exert a pro-inflammatory, anti-tumor effect to control GBMs. However, imaging methods capable of differentiating tumor progression from immunotherapy treatment effects have been lacking, making timely assessment of treatment response difficult. We showed that tracking monocytes using iron oxide nanoparticle (USPIO) with MRI can be a sensitive imaging method to detect therapy response directed at the innate immune system. METHODS: We implanted syngeneic mouse glioma stem cells into C57/BL6 mice and treated the animals with either niacin (a stimulator of innate immunity) or vehicle. Animals were imaged using an anatomical MRI sequence, R2* mapping, and quantitative susceptibility mapping (QSM) before and after USPIO injection. RESULTS: Compared to vehicles, niacin-treated animals showed significantly higher susceptibility and R2*, representing USPIO and monocyte infiltration into the tumor. We observed a significant reduction in tumor size in the niacin-treated group 7 days later. We validated our MRI results with flow cytometry and immunofluoresence, which showed that niacin decreased pro-inflammatory Ly6C high monocytes in the blood but increased CD16/32 pro-inflammatory macrophages within the tumor, consistent with migration of these pro-inflammatory innate immune cells from the blood to the tumor. CONCLUSION: MRI with USPIO injection can detect therapeutic responses of innate immune stimulating agents before changes in tumor size have occurred, providing a potential complementary imaging technique to monitor cancer immunotherapies. MANUSCRIPT HIGHLIGHT: We show that iron oxide nanoparticles (USPIOs) can be used to label innate immune cells and detect the trafficking of pro-inflammatory monocytes into the glioblastoma. This preceded changes in tumor size, making it a more sensitive imaging technique.


Assuntos
Glioblastoma , Glioma , Niacina , Camundongos , Animais , Monócitos/patologia , Glioma/patologia , Modelos Animais , Imageamento por Ressonância Magnética/métodos
15.
Braz. j. biol ; 83: 1-9, 2023. ilus, tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1468866

RESUMO

Physids belong to Class Gastropoda; Phylum Mollusca have important position in food web and act as bio indicators, pests and intermediate host. Being resistant these are called cockroaches of malacology. Physid snails were collected from different water bodies of Faisalabad (Punjab) and were identified up to species using morphological markers. The morphometry of the specimens was carried out with the help of a digital Vernier caliper in millimeters (mm) using linear measurement of shell characters. Linear regression analysis of the AL/SW ratio vs AL and SL/SW ratiovs AL indicated that allometric growth exists only in Physa acuta when compared with P.gyrina and P. fontinalis. This study will lead to assess the status of the Physid species in Central Punjab. The Principal component analysis shows that the Component 1 (Shell Length) and component 2 (Shell Width) are the most prolific components and nearly 80 percent of the identification. The distance between P. acuta and P. fontinalis is 5.4699, P. acuta and P. gyrina is 7.6411, P. fontinalis and P. gyrina is 16.6080 showing that P. acuta resembles with P. fontinalis, and both these specimens donot resemble with P. gyrina. P.acuta is an invasive species and shows bioactivity making it a potent candidate for bioactive substances.


Os físidos pertencem à classe Gastropoda; o filo Mollusca possui importante posição na teia alimentar e atua como bioindicador, praga e hospedeiro intermediário. Por serem resistentes, são chamadas baratas de malacologia. Os caramujos físidos foram coletados em diferentes corpos d’água de Faisalabad (Punjab) e identificados até as espécies por meio de marcadores morfológicos. A morfometria dos corpos de prova foi realizada com auxílio de paquímetro digital Vernier em milímetros (mm) por meio de medida linear dos caracteres da casca. A análise de regressão linear da razão AL / SW vs. AL e razão SL / SW vs. AL indicou que o crescimento alométrico existe apenas em Physa acuta quando comparado com P. gyrina e P. fontinalis. Este estudo levará a avaliar a situação das espécies de físido no Punjab Central. A análise do componente principal mostra que o componente 1 (comprimento da casca) e o componente 2 (largura da casca) são os componentes mais prolíficos e quase 80% da identificação. A distância entre P. acuta e P. fontinalis é 5,4699, P. acuta e P. gyrina é 7,6411, P. fontinalis e P. gyrina é 16,6080, mostrando que P. acuta se assemelha a P. fontinalis, e ambos os espécimes não se parecem com P. gyrina. P. acuta é uma espécie invasora e apresenta bioatividade, tornando-se uma candidata potente para substâncias bioativas.


Assuntos
Animais , Moluscos/anatomia & histologia , Análise Discriminante
16.
Braz. j. biol ; 83: 1-8, 2023. map, ilus, tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1468867

RESUMO

Physids belong to Class Gastropoda; belong to Phylum Mollusca and being bioindicators, intermediate hosts of parasites and pests hold a key position in the ecosystem. There are three species of Genus Physa i.e. P. fontinalis, Physa acuta and P. gyrina water bodies of Central Punjab and were characterized on the basis of molecular markers High level of genetic diversity was revealed by polymorphic RAPD, however SSR markers were not amplified. The multivariate analysis revealed polymorphism ranging from 9.09 percent to 50 percent among the three Physid species. Total number of 79 loci were observed for the three species under study and 24 loci were observed to be polymorphic. These RAPD fragment(s) can be developed into co dominant markers (SCAR) by cloning and can be further sequenced for the development of the Physa species specific markers to identify the introduced and native species in Pakistan.


Os físidos pertencem à classe Gastropoda; pertencem ao filo Mollusca e, sendo bioindicadores, hospedeiros intermediários de parasitas e pragas, ocupam uma posição-chave no ecossistema. Existem três espécies do gênero Physa, ou seja, P. fontinalis, Physa acuta e P. gyrina em corpos d’água do Punjab Central e foram caracterizadas com base em marcadores moleculares. Alto nível de diversidade genética foi revelado por RAPD polimórfico, no entanto os marcadores SSR não foram amplificados. A análise multivariada revelou polimorfismo variando de 9,09% a 50% entre as três espécies de Physid. Um número total de 79 loci foi observado para as três espécies em estudo e 24 loci foram observados como polimórficos. Esses fragmentos RAPD podem ser desenvolvidos em marcadores codominantes (SCAR) por clonagem e podem ser posteriormente sequenciados para o desenvolvimento de marcadores específicos da espécie Physa para identificar as espécies introduzidas e nativas no Paquistão.


Assuntos
Animais , Moluscos/genética , Variação Genética
17.
Braz. j. biol ; 83: e246934, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1285605

RESUMO

Abstract Physids belong to Class Gastropoda; Phylum Mollusca have important position in food web and act as bio indicators, pests and intermediate host. Being resistant these are called cockroaches of malacology. Physid snails were collected from different water bodies of Faisalabad (Punjab) and were identified up to species using morphological markers. The morphometry of the specimens was carried out with the help of a digital Vernier caliper in millimeters (mm) using linear measurement of shell characters. Linear regression analysis of the AL/SW ratio vs AL and SL/SW ratio vs AL indicated that allometric growth exists only in Physa acuta when compared with P.gyrina and P. fontinalis. This study will lead to assess the status of the Physid species in Central Punjab. The Principal component analysis shows that the Component 1 (Shell Length) and component 2 (Shell Width) are the most prolific components and nearly 80 percent of the identification. The distance between P. acuta and P. fontinalis is 5.4699, P. acuta and P. gyrina is 7.6411, P. fontinalis and P. gyrina is 16.6080 showing that P. acuta resembles with P. fontinalis, and both these specimens donot resemble with P. gyrina. P.acuta is an invasive species and shows bioactivity making it a potent candidate for bioactive substances.


Resumo Os físidos pertencem à classe Gastropoda; o filo Mollusca possui importante posição na teia alimentar e atua como bioindicador, praga e hospedeiro intermediário. Por serem resistentes, são chamadas baratas de malacologia. Os caramujos físidos foram coletados em diferentes corpos d'água de Faisalabad (Punjab) e identificados até as espécies por meio de marcadores morfológicos. A morfometria dos corpos de prova foi realizada com auxílio de paquímetro digital Vernier em milímetros (mm) por meio de medida linear dos caracteres da casca. A análise de regressão linear da razão AL / SW vs. AL e razão SL / SW vs. AL indicou que o crescimento alométrico existe apenas em Physa acuta quando comparado com P. gyrina e P. fontinalis. Este estudo levará a avaliar a situação das espécies de físido no Punjab Central. A análise do componente principal mostra que o componente 1 (comprimento da casca) e o componente 2 (largura da casca) são os componentes mais prolíficos e quase 80% da identificação. A distância entre P. acuta e P. fontinalis é 5,4699, P. acuta e P. gyrina é 7,6411, P. fontinalis e P. gyrina é 16,6080, mostrando que P. acuta se assemelha a P. fontinalis, e ambos os espécimes não se parecem com P. gyrina. P. acuta é uma espécie invasora e apresenta bioatividade, tornando-se uma candidata potente para substâncias bioativas.


Assuntos
Animais , Caramujos , Espécies Introduzidas
18.
Braz. j. biol ; 83: e246984, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1285632

RESUMO

Abstract Physids belong to Class Gastropoda; belong to Phylum Mollusca and being bioindicators, intermediate hosts of parasites and pests hold a key position in the ecosystem. There are three species of Genus Physa i.e. P. fontinalis, Physa acuta and P. gyrina water bodies of Central Punjab and were characterized on the basis of molecular markers High level of genetic diversity was revealed by polymorphic RAPD, however SSR markers were not amplified. The multivariate analysis revealed polymorphism ranging from 9.09 percent to 50 percent among the three Physid species. Total number of 79 loci were observed for the three species under study and 24 loci were observed to be polymorphic. These RAPD fragment(s) can be developed into co dominant markers (SCAR) by cloning and can be further sequenced for the development of the Physa species specific markers to identify the introduced and native species in Pakistan.


Resumo Os físidos pertencem à classe Gastropoda; pertencem ao filo Mollusca e, sendo bioindicadores, hospedeiros intermediários de parasitas e pragas, ocupam uma posição-chave no ecossistema. Existem três espécies do gênero Physa, ou seja, P. fontinalis, Physa acuta e P. gyrina em corpos d'água do Punjab Central e foram caracterizadas com base em marcadores moleculares. Alto nível de diversidade genética foi revelado por RAPD polimórfico, no entanto os marcadores SSR não foram amplificados. A análise multivariada revelou polimorfismo variando de 9,09% a 50% entre as três espécies de Physid. Um número total de 79 loci foi observado para as três espécies em estudo e 24 loci foram observados como polimórficos. Esses fragmentos RAPD podem ser desenvolvidos em marcadores codominantes (SCAR) por clonagem e podem ser posteriormente sequenciados para o desenvolvimento de marcadores específicos da espécie Physa para identificar as espécies introduzidas e nativas no Paquistão.


Assuntos
Animais , Gastrópodes , Espécies Introduzidas , Paquistão , Filogenia , Ecossistema , Técnica de Amplificação ao Acaso de DNA Polimórfico
19.
Braz. j. biol ; 832023.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469082

RESUMO

Abstract Physids belong to Class Gastropoda; Phylum Mollusca have important position in food web and act as bio indicators, pests and intermediate host. Being resistant these are called cockroaches of malacology. Physid snails were collected from different water bodies of Faisalabad (Punjab) and were identified up to species using morphological markers. The morphometry of the specimens was carried out with the help of a digital Vernier caliper in millimeters (mm) using linear measurement of shell characters. Linear regression analysis of the AL/SW ratio vs AL and SL/SW ratio vs AL indicated that allometric growth exists only in Physa acuta when compared with P.gyrina and P. fontinalis. This study will lead to assess the status of the Physid species in Central Punjab. The Principal component analysis shows that the Component 1 (Shell Length) and component 2 (Shell Width) are the most prolific components and nearly 80 percent of the identification. The distance between P. acuta and P. fontinalis is 5.4699, P. acuta and P. gyrina is 7.6411, P. fontinalis and P. gyrina is 16.6080 showing that P. acuta resembles with P. fontinalis, and both these specimens donot resemble with P. gyrina. P.acuta is an invasive species and shows bioactivity making it a potent candidate for bioactive substances.


Resumo Os físidos pertencem à classe Gastropoda; o filo Mollusca possui importante posição na teia alimentar e atua como bioindicador, praga e hospedeiro intermediário. Por serem resistentes, são chamadas baratas de malacologia. Os caramujos físidos foram coletados em diferentes corpos dágua de Faisalabad (Punjab) e identificados até as espécies por meio de marcadores morfológicos. A morfometria dos corpos de prova foi realizada com auxílio de paquímetro digital Vernier em milímetros (mm) por meio de medida linear dos caracteres da casca. A análise de regressão linear da razão AL / SW vs. AL e razão SL / SW vs. AL indicou que o crescimento alométrico existe apenas em Physa acuta quando comparado com P. gyrina e P. fontinalis. Este estudo levará a avaliar a situação das espécies de físido no Punjab Central. A análise do componente principal mostra que o componente 1 (comprimento da casca) e o componente 2 (largura da casca) são os componentes mais prolíficos e quase 80% da identificação. A distância entre P. acuta e P. fontinalis é 5,4699, P. acuta e P. gyrina é 7,6411, P. fontinalis e P. gyrina é 16,6080, mostrando que P. acuta se assemelha a P. fontinalis, e ambos os espécimes não se parecem com P. gyrina. P. acuta é uma espécie invasora e apresenta bioatividade, tornando-se uma candidata potente para substâncias bioativas.

20.
Braz. j. biol ; 832023.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469083

RESUMO

Abstract Physids belong to Class Gastropoda; belong to Phylum Mollusca and being bioindicators, intermediate hosts of parasites and pests hold a key position in the ecosystem. There are three species of Genus Physa i.e. P. fontinalis, Physa acuta and P. gyrina water bodies of Central Punjab and were characterized on the basis of molecular markers High level of genetic diversity was revealed by polymorphic RAPD, however SSR markers were not amplified. The multivariate analysis revealed polymorphism ranging from 9.09 percent to 50 percent among the three Physid species. Total number of 79 loci were observed for the three species under study and 24 loci were observed to be polymorphic. These RAPD fragment(s) can be developed into co dominant markers (SCAR) by cloning and can be further sequenced for the development of the Physa species specific markers to identify the introduced and native species in Pakistan.


Resumo Os físidos pertencem à classe Gastropoda; pertencem ao filo Mollusca e, sendo bioindicadores, hospedeiros intermediários de parasitas e pragas, ocupam uma posição-chave no ecossistema. Existem três espécies do gênero Physa, ou seja, P. fontinalis, Physa acuta e P. gyrina em corpos dágua do Punjab Central e foram caracterizadas com base em marcadores moleculares. Alto nível de diversidade genética foi revelado por RAPD polimórfico, no entanto os marcadores SSR não foram amplificados. A análise multivariada revelou polimorfismo variando de 9,09% a 50% entre as três espécies de Physid. Um número total de 79 loci foi observado para as três espécies em estudo e 24 loci foram observados como polimórficos. Esses fragmentos RAPD podem ser desenvolvidos em marcadores codominantes (SCAR) por clonagem e podem ser posteriormente sequenciados para o desenvolvimento de marcadores específicos da espécie Physa para identificar as espécies introduzidas e nativas no Paquistão.

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