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1.
bioRxiv ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38746118

RESUMO

Background: Necrotizing enterocolitis (NEC) is an inflammatory gastrointestinal process that afflicts approximately 10% of preterm infants born in the United States each year, with a mortality rate of 30%. NEC severity is graded using Bell's classification system, from stage I mild NEC to stage III severe NEC. Over half of NEC survivors present with neurodevelopmental impairment during adolescence, a long-term complication that is poorly understood but can occur even after mild NEC. Although multiple animal models exist, none allow the experimenter to control nor represent the gradient of symptom severities seen in NEC patients. We bridge this knowledge gap by developing a graded murine model of NEC and studying its relationship with neuroinflammation across a range of NEC severities. Methods: Postnatal day 3 (P3) C57BL/6 mice were fed a formula containing different concentrations (0% control, 0.25%, 1%, 2%, and 3%) of dextran sodium sulfate (DSS). P3 mice were fed every 3 hours for 72-hours. We collected data on weight gain and behavior (activity, response, body color) during feeding. At the end of the experiment, we collected tissues (intestine, liver, plasma, brain) for immunohistochemistry, immunofluorescence, and cytokine and chemokine analysis. Results: Throughout NEC induction, mice fed higher concentrations of DSS died sooner, lost weight faster, and became sick or lethargic earlier. Intestinal characteristics (dilation, color, friability) were worse in mice fed with higher DSS concentrations. Histology revealed small intestinal disarray among mice fed all DSS concentrations, while higher DSS concentrations resulted in reduced small intestinal cellular proliferation and increased hepatic and systemic inflammation. In the brain, IL-2, G-CSF, and CXCL1 concentrations increased with higher DSS concentrations. Although the number of neurons and microglia in the CA1 hippocampal region did not differ, microglial branching was significantly reduced in DSS-fed mice. Conclusion: We characterize a novel graded model of NEC that recapitulates the full range of NEC severities. We show that mild NEC is sufficient to initiate neuroinflammation and microglia activation. This model will facilitate studies on the neurodevelopmental effects of NEC.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36112066

RESUMO

Predominantly androgen secreting juvenile granulosa cell tumors (JGCT) are uncommon and few reports exist in the literature. We present a case of a JGCT which presented with signs of prepubertal hyperandrogenism and insulin resistance to highlight the possible interaction between hyperandrogenemia and hyperinsulinism. We conducted chart review of a rare androgen secreting JGCT accompanied by hyperinsulinemia in a prepubertal patient. A 4-year-old girl presented with acanthosis nigricans and hyperinsulinism mimicking the Hyperandrogenism Insulin Resistance and Acanthosis Nigricans (HAIR-AN) syndrome at an age much younger than is typical for this diagnosis. Laboratory studies revealed elevated insulin, inhibin A and B, and total testosterone. All laboratory results normalized after unilateral salpingo-oophorectomy. The final diagnosis was Stage IA JGCT. This case highlights the importance of including ovarian tumors in the differential diagnosis when considering causes of virilization and insulin resistance. Our case illustrates the potential relationship between excess testosterone secretion and hyperinsulinemia and strengthens evidence that hyperandrogenemia may promote hyperinsulinism in ovarian disease.

3.
Chest ; 162(2): e77-e80, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35940666

RESUMO

CASE PRESENTATION: In July 2020, a previously healthy 6-year-old boy was evaluated in a pulmonary clinic in New York after two episodes of pneumonia in the previous 3 months. For each episode, the patient presented with cough, fever, and hemoptysis, all of which resolved with antibiotic therapy and supportive care. The patient never experienced dyspnea during these episodes of pneumonia. He was asymptomatic at the current visit. The patient had no history of travel, sick contacts, asthma, or bleeding disorders.


Assuntos
COVID-19 , Hemoptise , Criança , Dispneia , Hemoptise/diagnóstico , Hemoptise/etiologia , Hemoptise/terapia , Humanos , Pulmão , Masculino , Pandemias
4.
Brain Res ; 1736: 146699, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32027866

RESUMO

GABAA receptors (GABAAR) are inhibitory ion channels ubiquitously expressed in the central nervous system and play critical roles in brain development and function. Benzodiazepines are positive allosteric modulators of GABAAR, enhancing channel opening frequency when GABA is bound to the receptor. Midazolam is a commonly used benzodiazepine. It is frequently used for premature infants, but the long-term consequences of its use in this patient population are not well established. Here, we studied the acute effects of midazolam on immature synapses. Using a rodent organotypic hippocampal slice preparation, we evaluated how midazolam affects inhibitory synaptic transmission onto CA1 pyramidal neurons. We found that 1 µM midazolam enhances evoked inhibitory post synaptic currents (eIPSCs) at a holding potential of -60 mV. Similarly, 1 µM midazolam enhances miniature IPSCs (mIPSCs) in CA1 pyramidal neurons at holding potentials of -60 mV and -30 mV. At depolarized holding potentials, however, midazolam no longer enhances mIPSCs. Depolarization of the postsynaptic cell by itself increases mIPSC decay, which occludes the allosteric effects of midazolam. These results provide insight into how a benzodiazepine and membrane voltage may modulate GABAAR function in developing circuits.


Assuntos
Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Midazolam/farmacologia , Receptores de GABA-A/metabolismo , Regulação Alostérica/efeitos dos fármacos , Regulação Alostérica/fisiologia , Animais , Benzodiazepinas/metabolismo , Benzodiazepinas/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Midazolam/metabolismo , Técnicas de Patch-Clamp , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiologia , Receptores de GABA-A/efeitos dos fármacos , Sinapses/fisiologia , Transmissão Sináptica/fisiologia
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