RESUMO
Nontraumatic anterior spinal artery syndrome (ASAS) is an extremely rare clinical condition in pediatric populations with a mostly unknown underlying etiology. Here we discuss the case of a previously healthy 14-year-old girl presenting with sudden onset acute flaccid paralysis to the emergency department. A spinal STIR/DWI MRI revealed hyperintensities extending from cervical vertebrae C3-6, consistent with the diagnosis of ASAS. In order to determine any precipitating causes of ASAS, we also extensively investigated established potential risk factors for ASAS in our patient and noticed that she had a marked folate deficiency requiring folic acid supplementation to prevent future episodes of ASAS as well as to repair the patient's injured spinal cord. Interestingly, the patient did not display elevated levels of homocysteine nor did she possess the three pathogenic MTHFR mutations characteristic of ASAS. Although her folate deficiency did not cause responsive hyperhomocysteinemia, and she did not have pathogenic MTHFR mutations that impair the function of methylenetetrahydrofolate reductase in folate cycle, we suggest that isolated folate deficiency may play a role in adolescent cases of ASAS that, once identified, would require prompt identification and early intervention to improve the prognosis of these patients.
RESUMO
A 35-year-old woman with unintentional weight gain, hyperpigmentation of bilateral palms, and general fatigue was initially suspected of Cushing's syndrome or adrenal insufficiency based on the isolated elevation of the plasma adrenocorticotropic hormone (ACTH) level (113.0 pg/mL) in the Siemens ACTH Immulite assay (ACTH [Immulite]). However, both of the diagnoses were excluded by screening tests including the overnight dexamethasone suppression test, the 24-hour urinary free cortisol excretion, and the ACTH stimulation test in spite of the consistent elevation of the plasma ACTH levels. We speculated that the existence of the immunoassay interference may be the underlying cause because the plasma ACTH level analyzed by the CIS Bio International ELSA-ACTH immunoassay (ELSA-ACTH) was within the normal range. After reviewing our case and several reported cases of falsely elevated plasma ACTH levels, we conclude that when discrepancy between clinical symptoms and laboratory measurements exists, medical practitioners ought to rely on formal diagnostic criteria rather than misleading laboratory results to avoid misdiagnosis or even unnecessary invasive testing and procedures. In addition, current methods for investigation and elimination of immunoassay interferences should be applied with caution due to variable efficacy and inevitable deviations.
Assuntos
Hormônio Adrenocorticotrópico , Síndrome de Cushing , Adulto , Síndrome de Cushing/diagnóstico , Feminino , HumanosRESUMO
Chromosome 17p13.3 microduplication syndrome is considered a multisystem disorder that results in a wide variety of clinical manifestations including dysmorphic facial characteristics, brain structural malformations, developmental restriction, growth restriction, and neurocognitive disorders. The two major classes of chromosome 17p13.3 microduplication, which have different clinical presentations, are associated with specific genetic regions. Among the various known phenotypes, scattered cases with congenital heart disease (CHD) have been reported for both classes of chromosome 17p13.3 microduplication syndrome. Unfortunately, there is insufficient understanding of the correlation between chromosome anomaly induced alterations in gene expression and aberrant cardiac development, and thus early diagnosis of CHD among patients with chromosome 17p13.3 microduplication is difficult without routine prenatal cardiac assessment. One such congenital heart anomalies known to affect a substantial number of newborns worldwide is ventricular septal defect (VSD), which has been found in 17p13.3 microduplication carriers, and seems to sometimes undergo spontaneous closure. We report an unprecedented case of moderate sized perimembranous-outlet VSD and congestive heart failure (CHF) in a Chinese Han male infant with a class II chromosome 17p13.3 microduplication. Despite the fact that cytogenic testing and fetal echocardiography confirmed a 249-Kb chromosome duplication within 17p13.3 that encompassed the PAFAH1B1 gene and showed the presence of VSD during prenatal period, this patient still developed a range of symptoms including sustained prolonged feeding, dyspnea, diaphoresis and retarded growth. A physical examination indicated hepatomegaly and a grade III/VI pan-systolic murmur along the left upper sternal border. Laboratory testing showed a high serum pro-B-type natriuretic peptide (pro-BNP). Imaging studies revealed cardiomegaly and a persistent VSD with related pulmonary stenosis. Since the clinical findings were compatible with CHF, we provided mainline treatment with digoxin, captopril, and furosemide, as well as fluid restriction. Despite sustained poor weight gain, the feeding behavior and the respiratory conditions of the patient improved gradually. This case report and literature review suggest that patients carrying chromosome 17p13.3 microduplication who have VSD may have an increased risk of developing CHF as young infants and hence a comprehensive cardiac evaluation is warranted to allow the early diagnosis and management of any severe heart anomalies.
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Previous studies have shown that the experimental models of hypoxia-reoxygenation (H/R) mimics the physiological conditions of ischemia-reperfusion and induce oxidative stress and injury in various types of organs, tissues, and cells, both in vivo and in vitro, including human lung adenocarcinoma epithelial cells. Nonetheless, it had not been reported whether H/R affected proliferation, apoptosis, and expression of stem/progenitor cell markers in the bronchial epithelial cells. In this study, we investigated differential effects of consecutive hypoxia and intermittent 24/24-h cycles of H/R on human bronchial epithelial (HBE) cells derived from the same-race and age-matched healthy subjects (i.e., NHBE) and subjects with chronic obstructive pulmonary disease (COPD) (i.e., DHBE). To analyze gene/protein expression during differentiation, both the NHBE and DHBE cells at the 2nd passage were cultured at the air-liquid interface (ALI) in the differentiation medium under normoxia for 3 days, followed by either culturing under hypoxia (1% O2) for consecutively 9 days and then returning to normoxia for another 9 days, or culturing under 24/24-h cycles of H/R (i.e., 24 h of 1% O2 followed by 24 h of 21% O2, repetitively) for 18 days in total, so that all differentiating HBE cells were exposed to hypoxia for a total of 9 days. In both the normal and diseased HBE cells, intermittent H/R significantly increased HIF1A, BMP4, NOTCH1, MKI67, OCT4, and MUC5AC expression, while consecutive hypoxia significantly decreased NKX2-1, NOTCH3, HEY1, CC10, and FOXJ1 expression. Inhibition of HIF1A or NKX2-1 expression by siRNA transfection respectively decreased BMP4/NOTCH1/MKI67/OCT4/MUC5AC and NOTCH3/HEY1/CC10/FOXJ1 expression in the HBE cells cultured under intermittent H/R to the same levels under normoxia. Overexpression of NKX2-1 via cDNA transfection caused more than 2.8-fold increases in NOTCH3, HEY1, and FOXJ1 mRNA levels in the HBE cells cultured under consecutive hypoxia compared to the levels under normoxia. Taken together, our results show for the first time that consecutive hypoxia decreased expression of the co-regulated gene module NOTCH3/HEY1/CC10 and the ciliogenesis-inducing transcription factor gene FOXJ1 via NKX2-1 mRNA downregulation, while intermittent H/R increased expression of the co-regulated gene module BMP4/NOTCH1/MKI67/OCT4 and the predominant airway mucin gene MUC5AC via HIF1A mRNA upregulation.
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Daily fluctuation of permethrin-resistance was found in adult mosquito Aedes aegypti, the major vector of dengue viruses in Taiwan. We hypothesized there is a relationship between resistance and the circadian clock. To test our hypothesis we correlated changes in the knock-down time (KT(50)) response to permethrin with the expression of the pyrethroid-resistant gene CYP9M9 and the clock gene period (per) during a 12:12h photoperiodic cycle. Rhythmic expression of per peaked at early scotophase of the light-dark cycle and at early subjective night in constant darkness. The values of KT(50) and the expression of CYP9M9 also exhibited circadian rhythms in both susceptible and permethrin-resistant mosquito strains, from which we inferred a link to the circadian clock. The KT(50) was significantly longer in the light than in the dark phase, and the level of CYP9M9 mRNA was maximal in early scotophase, dropped to a minimum in the midnight and then slowly increased through the photophase. Existence of a clock control over mosquito sensitivity to permethrin was further indicated by reduced expression of CYP9M9 and reduced mosquito resistance to permethrin after temporal silencing of the per gene. These data provide the first evidence on the circadian control of insect resistance to permethrin.
Assuntos
Aedes/fisiologia , Ritmo Circadiano/fisiologia , Regulação da Expressão Gênica/fisiologia , Insetos Vetores/fisiologia , Resistência a Inseticidas/fisiologia , Permetrina , Aedes/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Primers do DNA/genética , Inativação Gênica , Insetos Vetores/metabolismo , Dose Letal Mediana , Proteínas Circadianas Period/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TaiwanRESUMO
The cell distribution and immunoreactivity (ir) against period (PER), pigment dispersing factor (PDF) and corazonin (CRZ), were compared between adults and nymphs in the central nervous system of the German cockroach. Although PER-ir cells in the optic lobes (OL) were expressed in the nymphs from the first instar, the links between major clock cells became more elaborated after second/third instar. A circadian rhythm of locomotion was initiated at the fourth/fifth instar. The results suggest that the clock was running from hatching, but the control network needed more time to develop. In addition, the putative downstream regulators, PDF-ir and CRZ-ir, are co-localized in various regions of the brain, indicating potential output routes of the circadian clock. CRZ-ir cells with typical morphology of neurosecretory cells in the dorsolateral protocerebrum send out three neural fibers to reach the ipsilateral corpora cardiaca (CC), the antennal lobe and two hemispheres of the protocerebrum. Based on co-localization with some PER-ir/PDF-ir cells, the CRZ-ir cells have the potential to serve as a bridge between circadian neural signals and endocrine regulation. Based on PDF's role in the regulation of locomotion, our results support the finding that the locomotor circadian rhythm is possibly controlled by a hormonal route.