Identification of Hypothalamic Glucoregulatory Neurons That Sense and Respond to Changes in Glycemia.

To investigate whether glucoregulatory neurons in the hypothalamus can sense and respond to physiological variation in the blood glucose (BG) level, we combined continuous arterial glucose monitoring with continuous measures of the activity of a specific subset of neurons located in the hypothalamic ventromedial nucleus that express pituitary adenylate cyclase activating peptide (VMNPACAP neurons) obtained using fiber photometry. Data were collected in conscious, free-living mice during a 1-h baseline monitoring period and a subsequent 2-h intervention period during which the BG level was raised either by consuming a chow or a high-sucrose meal or by intraperitoneal glucose injection. Cross-correlation analysis revealed that, following a 60- to 90-s delay, interventions that raise the BG level reliably associate with reduced VMNPACAP neuron activity (P < 0.01). In addition, a strong positive correlation between BG and spontaneous VMNPACAP neuron activity was observed under basal conditions but with a much longer (∼25 min) temporal offset, consistent with published evidence that VMNPACAP neuron activation raises the BG level. Together, these findings are suggestive of a closed-loop system whereby VMNPACAP neuron activation increases the BG level; detection of a rising BG level, in turn, feeds back to inhibit these neurons. To our knowledge, these findings constitute the first evidence of a role in glucose homeostasis for glucoregulatory neurocircuits that, like pancreatic ß-cells, sense and respond to physiological variation in glycemia. ARTICLE HIGHLIGHTS: By combining continuous arterial glucose monitoring with fiber photometry, studies investigated whether neurons in the murine ventromedial nucleus that express pituitary adenylate cyclase activating peptide (VMNPACAP neurons) detect and respond to changes in glycemia in vivo. VMNPACAP neuron activity rapidly decreases (within <2 min) when the blood glucose level is raised by either food consumption or glucose administration. Spontaneous VMNPACAP neuron activity also correlates positively with glycemia, but with a longer temporal offset, consistent with reports that hyperglycemia is induced by experimental activation of these neurons. Like pancreatic ß-cells, neurons in the hypothalamic ventromedial nucleus appear to sense and respond to physiological variation in glycemia.

Disseminated Histoplasmosis: A Rare Cause of Pancytopenia in an Immunocompromised Patient.

Histoplasma capsulatum  is a dimorphic fungus endemic to North and South America. This organism's ubiquity outside the traditionally defined region of the Mississippi and Ohio River Valley makes it an important yet often forgotten cause of systemic inflammatory disease. Progressive disseminated histoplasmosis is an uncommon opportunistic infection, largely affecting immunocompromised individuals with defects in T-cell immunity. The initial manifestations of disseminated histoplasmosis present non-specifically with symptoms such as fever, malaise, anorexia, and weight loss. Given this fungi's endemic nature, disseminated histoplasmosis is an essential disease for physicians to diagnose accurately. Diagnosis can be established through antigen detection in the blood or urine, although the gold standard is tissue diagnosis or fungal culture. Treatment of mild to moderate disease consists of an itraconazole regimen for a year, yet severe disease requires an additional 14-day induction therapy with amphotericin B. We present a case of disseminated histoplasmosis in a breast cancer patient, recently treated with neoadjuvant chemotherapy, who presented with new-onset pancytopenia.