Velusetrag rescues GI dysfunction, gut inflammation and dysbiosis in a mouse model of Parkinson's disease

: In patients with Parkinson's disease (PD), constipation is common, and it appears in a prodromal stage before the hallmark motor symptoms. The present study aimed to investigate whether Velusetrag, a selective 5‑HT4 receptor agonist, may be a suitable candidate to improve intestinal motility in a mouse model of PD. Five months old PrP human A53T alpha-synuclein transgenic (Tg) mice, which display severe constipation along with decreased colonic cholinergic transmission already at 3 months, were treated daily with the drug for 4 weeks. Velusetrag treatment reduced constipation by significantly stimulating both the longitudinal and circular-driven contractions and improved inflammation by reducing the level of serum and colonic IL1β and TNF-α and by decreasing the number of GFAP-positive glia cells in the colon of treated mice. No significant downregulation of the 5-HT4 receptor was observed but instead Velusetrag seemed to improve axonal degeneration in Tgs as shown by an increase in NF-H and VAChT staining. Ultimately, Velusetrag restored a well-balanced intestinal microbial composition comparable to non-Tg mice. Based on these promising data, we are confident that Velusetrag is potentially eligible for clinical studies to treat constipation in PD patients

Cholesterol Emboli Syndrome in Type 2 Diabetes: The Disease History of a Case Evaluated with Renal Scintigraphy

BACKGROUND: Cholesterol crystal emboli syndrome (CCE) is an emerging disease, whose progression reflects the currently observed increase in cardiovascular diseases. Diagnostic criteria shifted from pathological to clinical criteria: creatinine increase, skin lesions, recent endovascular interventions and severe vasculopathy). Diabetes, hypertension and diffuse vascular disease are inter-linked, major risk factors. The role of imaging techniques in the diagnosis and treatment of the disease has been little investigated thus far. The AIM of this report is to describe a case exemplifying the potentials for renal scintigraphy in CCE, an emerging disease in type 2 diabetic patients. THE CASE: a 75 year-old, type 2 diabetic for over 15 years, obese, hypertensive white man was referred to the Nephrology Unit after an acute coronary syndrome. Stenosis of the left renal artery was diagnosed from the angiography. Serum creatinine (baseline: 1.9 mg/dl) increased after multiple angioplasties to 3.3 mg/dl, then slowly returned towards baseline (2.2 mg/dl), but rose, on referral, to 3.9 mg/dl, with an increase in acute phase reactants and peripheral livedo reticularis, a picture highly suggestive of CCE. The first renal scintiscan showed a reduction of the parenchymal phase, and a non-homogeneous parenchymal pattern in the right dominant kidney. The patient was started on corticosteroid therapy with a prompt decrease in creatinine; four days later (creatinine 2.5 mg/dl) a second scintiscan showed an improvement of the peak time and of the radionuclide parenchymal transit, and was further confirmed two months later (creatinine 2.2 mg/dl). No modification was detected in the left kidney, presumably mechanically "protected" from the cholesterol shedding by the stenosis. CONCLUSIONS: This is the first description of an imaging demonstration of the morpho-functional substratum to the rapid clinical response of corticosteroid therapy in a case of CCE and type 2 diabetes, underlining the potential of 99mTc-MAG3 dynamic scintiscan in this disease