Water- and fat-suppressed proton projection MRI (WASPI) of rat femur bone.

Investigators often study rats by microCT to investigate the pathogenesis and treatment of skeletal disorders in humans. However, microCT measurements provide information only on bone mineral content and not the solid matrix. CT scans are often carried out on cancellous bone, which contains a significant volume of marrow cells, stroma, water, and fat, and thus the apparent bone mineral density (BMD) does not reflect the mineral density within the matrix, where the mineral crystals are localized. Water- and fat-suppressed solid-state proton projection imaging (WASPI) was utilized in this study to image the solid matrix content (collagen, tightly bound water, and other immobile molecules) of rat femur specimens, and meet the challenges of small sample size and demanding submillimeter resolution. A method is introduced to recover the central region of k-space, which is always lost in the receiver dead time when free induction decays (FIDs) are acquired. With this approach, points near the k-space origin are sampled under a small number of radial projections at reduced gradient strength. The typical scan time for the current WASPI experiments was 2 hr. Proton solid-matrix images of rat femurs with 0.4-mm resolution and 12-mm field of view (FOV) were obtained. This method provides a noninvasive means of studying bone matrix in small animals.     

Indirect dopamine agonists augment the locomotor activating effects of the kappa-opioid receptor agonist U-50,488 in preweanling rats

kappa-Opioid receptor agonists (e.g., enadoline or U-50,488) increase the locomotor activity of preweanling rats, while the same drugs depress the locomotor activity of adults. Curiously, direct stimulation of dopamine (DA) D2-like receptors fully attenuates the U-50,488-induced locomotor activity of preweanling rats. The purpose of the present study was to determine whether indirect DA agonists (i.e., cocaine, methylphenidate, and amphetamine) would also attenuate U-50,488's behavioral effects. In two experiments, 17-day-old rats were injected with saline or U-50,488 (5 mg/kg, sc) and locomotor activity and stereotyped sniffing were assessed. After 20 min, the saline- and U-50,488-pretreated rats were injected with saline, cocaine (5, 10, or 20 mg/kg, i.p.), methylphenidate (10 or 20 mg/kg, i.p.), amphetamine (2.5 or 5 mg/kg, i.p.), or the direct D2-like receptor agonist NPA (1 mg/kg, i.p.). As expected, U-50,488 dramatically enhanced the locomotor activity of 17-day-old rats, while attenuating the stereotyped sniffing caused by indirect and direct DA agonists. All three indirect DA agonists augmented U-50,488's locomotor activating effects across the initial 10 min of testing and then activity declined to U-50,488 control values. Direct stimulation of DA receptors produced nearly opposite effects because NPA attenuated U-50,488-induced locomotor activity across the entire testing session. It is uncertain why direct and indirect DA agonists affected U-50,488-induced locomotor activity differently, but the relative amount of DA D1-like receptor activation is probably not responsible.     

Survival with total occlusion of left main coronary artery

Complete occlusion of the left main coronary artery is considered to be a terminal event in most cases. We describe two patients with this lesion who underwent successful coronary bypass surgery with complete relief of symptoms and long-term survival. The angiographic findings and clinical management of the two patients are discussed.     

Novel CARD9 mutation in a patient with chronic invasive dermatophyte infection (tinea profunda)

Caspase Recruitment Domain Family Member 9 (CARD9) is an adaptor molecule that drives antifungal activity of macrophages and neutrophils in the skin. Autosomal recessive loss-of-function mutations in CARD9 confer increased susceptibility to invasive disease with select fungi in non-immunosuppressed patients. We report on a patient with X-linked ichthyosis complicated by chronic cutaneous invasive dermatophyte infection. We identified a previously reported c.271T>C (p.Y91H) mutation and a novel intronic c.1269+18G>A mutation in CARD9 underlying recurrent deep dermatophytosis in this patient despite various antifungals for over three decades. Our case highlights susceptibility to invasive dermatophytosis related to autosomal recessive CARD9 deficiency and illustrates the range of CARD9 mutations to be pursued in immunocompetent patients with unexplained deep dermatophyte infections. Further studies are needed to define the best therapeutic regimen.