Perivascular adipose tissue (PVAT) exerts an anti‐contractile effect on blood vessels in healthy individuals, a mechanism lost in obesity‐related hypertension. To understand this process, we must first investigate the role of the functional adrenergic system residing within PVAT. We have shown that PVAT contains functional norepinephrine (NE), and that PVAT adipocytes have NE transporters, similar to sympathetic neurons. We hypothesize that NE is stored in vesicles within PVAT adipocytes, and that the vesicular monoamine transporter (VMAT) is used to do so. High‐performance liquid chromatography showed the presence of NE in normal male Sprague Dawley rat superior mesenteric artery (SMPVAT; 503.60 ± 34.70 ng/g tissue) and mesenteric (MPVAT; 148.20 ± 15.00 ng/g tissue) PVATs (N=6). Using immunofluorescence, we tested for VMAT1 and VMAT2 in these PVATs (N=6), and both transporters were present surrounding the lipid of the adipocytes. Immunofluorescence of MPVAT (N=4) and SMPVAT (N=4) revealed the co‐localization of NE and VMAT2 surrounding the lipid of PVAT adipocytes, and especially concentrated around the nucleus. We developed a protocol imaging live primary rat MPVAT adipocytes to capture real‐time uptake of Mini202, a fluorescent VMAT probe functioning as a false neurotransmitter (N=4). Cells were stained with 500 μM Mini202 (see data table). Addition of Rose Bengal (100 μM), a potent VMAT inhibitor, significantly reduced Mini202 signal. Addition of plasma membrane transporter inhibitors, nisoxetine (NE transporter, 10 mM) and corticosterone (organic cation 3 transporter, 10 mM) also significantly reduced Mini202 signal. Interestingly, immunofluorescence results support that neither VMAT1 (N=4) nor VMAT2 (N=4) is present in retroperitoneal adipocytes, suggesting that perivascular adipocytes are unique in their ability to store NE. This study supports a new function of perivascular adipocytes in storing amines and provides a basis for understanding NE storage by PVAT in obesity‐related hypertension. Support or Funding Information Funding provided by NIH NHLBI PO1HL70687 and the APS UGREF This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cumulative lifetime adversity and social support were investigated as determinants of psychosocial adjustment (esteem, distress, hopefulness, positive outlook/future aspirations, and sense of purpose) over 12 months in 6–10‐years‐old HIV‐infected, HIV‐exposed uninfected and HIV‐unexposed uninfected children from Uganda. Each determinant and psychosocial adjustment indicator was self‐reported using standardized questionnaires administered at baseline, 6, and 12 months. Linear mixed effects models were used to relate time‐varying lifetime adversity and social support to psychosocial adjustment over 12 months. Regardless of HIV status, higher adversity predicted lower esteem (coefficient b = −2.98, 95% confidence interval (CI): [−4.62, −1.35]) and increased distress (b =3.96, 95% CI: [1.29, 6.62]) but was not associated with hopefulness, positive outlook or sense of purpose. Low social support predicted higher distress (b =9.05, 95% CI: [7.36, 10.73]), lower positive outlook (b = −10.56, 95% CI: [−2.34, −8.79]) and low sense of purpose (b = −9.90, 95% CI: [−11.44, −8.36]) over 12 months. Pragmatic interventions that enhance coping with adversity and provide emotional/instrumental support should be tested for effectiveness in promoting resilient psychosocial adjustment trajectory in vulnerable children.
Dietary Fructose is implicated in the development of hypertension, diabetes and metabolic syndrome. Rats supplemented with 20% fructose develop hypertension, hypertriglyceridemia, and hyperglycemia after 8 weeks (Mamikutty N,et al. Biomed Res Int. '14). We hypothesized rats given a fructose‐enriched diet mimicking the upper range consumption in the US would cause salt‐sensitive hypertension prior to the onset of metabolic abnormalities. Groups of 8‐11 rats were given a normal rat chow diet, supplemented with either 1% NaCl, 20% fructose, or 1% NaCl plus 20% fructose in their drinking water over 4 weeks. Systolic blood pressure and body weights were monitored and 24 hour urine and blood collected at 4 weeks. After 4 weeks, systolic blood pressure was significantly increased by 10 ±4 mmHg (p<0.05) only in the fructose plus salt group. Growth rates were similar in all four groups (5.4 ± 0.4 g/day). Plasma electrolytes and glycemic indices were also similar. Plasma renin activity (PRA) was similar in control vs fructose rats (2.51±0.72 vs 2.71 ±0.90 ng AngI/ml/hr, respectively) but was suppressed by 80% (0.43 ±0.07 ngAng1/ml/hr) in rats fed 1% NaCl. However, fructose feeding prevented high salt induced‐suppression of PRA (1.89 ±0.43 ngAng1/ml/hr). Sodium excretion was elevated in both groups receiving NaCl. We conclude addition of salt to a fructose‐enriched diet induced salt‐sensitive hypertension prior to other pathologies. The blunting of salt‐induced suppression of PRA by fructose suggests it alters the sensitivity of renin secretion to salt intake and this may contribute to the increase in blood pressure.
Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a progressively debilitating, frequently fatal disease caused by autoantibodies against the NMDA receptor. Risk of delayed treatment is high due to variable presentations, lack of awareness and potential false negative diagnostic studies. In this case report, a woman in her 20s presented with psychiatric manifestations and rapidly declined. Dyskinetic movements and dysautonomia were observed. Initial cerebrospinal fluid and serum anti-NMDA receptor antibodies were negative. MRI was inconclusive. Electroencephalography demonstrated extreme delta brush. Pelvic CT revealed an adnexal teratoma. She remained refractory to treatment until day 126 when, after two cycles of cyclophosphamide, she started to improve. She participated in rehabilitation with eventual discharge home on day 269. Recognising the variable presentations of anti-NMDA receptor encephalitis is important in avoiding misdiagnosis and delayed treatment. If clinical suspicion remains high despite negative results, repeat testing should be pursued. Clinical response should guide treatment decisions in refractory cases.
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