Update and Mutational Analysis of SLC20A2: A Major Cause of Primary Familial Brain Calcification

Primary familial brain calcification (PFBC) is a heterogeneous neuropsychiatric disorder, with affected individuals presenting a wide variety of motor and cognitive impairments, such as migraine, parkinsonism, psychosis, dementia, and mood swings. Calcifications are usually symmetrical, bilateral, and found predominantly in the basal ganglia, thalamus, and cerebellum. So far, variants in three genes have been linked to PFBC: SLC20A2, PDGFRB, and PDGFB. Variants in SLC20A2 are responsible for most cases identified so far and, therefore, the present review is a comprehensive worldwide summary of all reported variants to date. SLC20A2 encodes an inorganic phosphate transporter, PiT‐2, widely expressed in various tissues, including brain, and is part of a major family of solute carrier membrane transporters. Fifty variants reported in 55 unrelated patients so far have been identified in families of diverse ethnicities and only few are recurrent. Various types of variants were detected (missense, nonsense, frameshift) including full or partial SLC20A2 deletions. The recently reported SLC20A2 knockout mouse will enhance our understanding of disease mechanism and allow for screening of therapeutic compounds. In the present review, we also discuss the implications of these recent exciting findings and consider the possibility of treatments based on manipulation of inorganic phosphate homeostasis.     

Contrast agents in abdominal imaging: current and future directions

Magnetic resonance imaging is an established imaging method for the evaluation of the abdomen. Accurate assessment of the liver, spleen, pancreas, bile ducts, vascular structures, and retroperitoneal organs (eg, the kidneys, the collecting system, and the adrenals) are possible on MR imaging. The intravenous administration of MR contrast agents can frequently improve the examination and provide more specific diagnoses. The advent of more specific, "hepatobiliary" contrast agents has further improved the differential diagnostic process, particularly for MR imaging of the liver. The availability of orally administered MR contrast agents has further extended the range of abdominal applications, making MR imaging of the small bowel and the colon established imaging procedures.     

Prognostic value of persistent thallium-201 defects that become reversible after reinjection in patients with chronic myocardial infarction

Background

The presence of defects at stress-redistribution thallium-201 scintigraphy is related to a higher risk of cardiac events. However, the prognostic value of defects that become reversible after reinjection is not known. In this study we evaluated the prognostic contribution of stress-redistribution-reinjection with special regard to 3-hour fixed defects that become reversible after reinjection.

Methods and Results

We studied 122 patients with chronic myocardial infarction (>2 months) and suspected or known residual ischemia, with stress-redistribution-reinjection planar scintigraphy. Thallium scans were analyzed by three observers (three segments per view, 5-point score) and classified as normal, fixed, and reversible. The lung/heart ratio was also calculated. At a median follow-up of 47 months, 10 patients had hard events (four deaths and six myocardial infarctions) (group I), 12 patients had unstable angina (group II), 12 patients underwent planned coronary artery bypass grafting or percutaneous transluminal coronary angioplasty (group III), and 86 patients had no events (group IV). The presence of fixed defects that became reversible after reinjection did not identify patients at higher risk. The number of reversible defects at 3 hours was significantly higher only in patients who underwent revascularization. Unstable angina was not predicted by any scintigraphic pattern. The variables that were statistically related to hard events by univariate analysis were increased lung uptake, reversible cavity dilation, and the number of fixed defects that remained fixed after reinjection. By Cox multivariate analysis, the strongest predictor of hard events was the presence of more than three fixed defects that remained fixed after reinjection as a marker of irreversible myocardial damage.

Conclusions

²⁰¹TI reinjection is a useful approach for not only detecting viable myocardium but also risk stratification in patients with chronic myocardial infarction.     

Potent relaxant effect of a Celastrus paniculatus extract in the rat and human ileum

Ethnopharmacological importance

Celastrus paniculatus Willd. (Celastraceae) is an Ayurvedic remedy used for the treatment of a number of diseases, including bowel spasms.

Aim of the study

To investigate the mode of the relaxing action of a methanolic extract prepared from the seeds of Celastrus paniculatus (CPE, 0.0001–10 μg/mL) in the rat ileum and to try to confirm on human tissues the intestinal pharmacological activity of the extract.

Materials and methods

The relaxant effect of CPE was studied in vitro by evaluating its effect on the spontaneous contractions of the isolated ileum.

Results

CPE exerted a tetrodotoxin- and ω-conotoxin-resistant inhibitory effect on rat ileum motility (IC₅₀: 0.24 ± 0.02 μg/mL; E_max: 99.0 ± 0.60%). The inhibitory effect was reduced by nifedipine but not by cyclopiazonic acid. Experiments with specific antagonists enabled us to exclude the involvement of the main endogenous spasmogenic (i.e. acetylcholine and tachykinins) and relaxing (noradrenaline, nitric oxide, ATP) compounds. CPE also relaxed the isolated human ileum (IC₅₀: 0.26 ± 0.02 μg/mL; E_max: 99.1 ± 0.46%).

Conclusion

It is concluded that (i) CPE exerted a powerful myogenic and L-type Ca²⁺-dependent relaxing effect in the isolated rat ileum and that (ii) the human ileum is sensitive to the inhibitory effect of CPE. If confirmed in vivo, our data could explain the traditional use of this herb in the treatment of intestinal spasms.     

Outcomes of endoscopic sinus surgery in adult lung transplant patients with cystic fibrosis

European Archives of Oto-Rhino-Laryngology - Cystic Fibrosis (CF) is the most common autosomal recessive disease in Caucasian population. Due to its pathological mechanism, chronic rhino sinusitis...     

Effect of infusion and withdrawl of glucose and insulin on gas exchange in injured ventilated patients

To evaluate the effect induced on gas exchange and on urea excretion by glucose and insulin infusion in injured patients. The magnitude and time necessary for the full development of the metabolic effect were investigated. Six injured patients were investigated. During the first 24 hours, the fasting period, patients received 1 mg/kg^*min of glucose; during the second 24 hours, the treatment period, infusion was increased to about the 95% of the energy production rate; during the last 8 hours, (stop period) the infusion rate was again set to 1 mg/kg^*min. Gas exchange was determined in two consecutive 12-hour series, for 30 minutes every hour, either during a stabilized treatment or after its variation. Urea excretion was determinated on 4-hour samples. With respect to the fasting period, during the last 4 hours of the treatment period, the energy production rate did not vary; urea excretion (−25%) and oxygen consumption (−9%) decreased significantly. Carbon dioxide production (+16%), total respiratory quotient, and minute ventilation (+5%) increased significantly. Carbon dioxide production varied linearly with time (glucose infusion ⁺1.74 mL/min^*m2^*h, P <.05; glucose withdrawal −1.89 mL/min^*m2^*h, P < .01). Minute ventilation decreased only during the withdrawal period by 65 mL/ min^*m2^*h (P < .05). The infusion of glucose and insulin, in an amount slightly lower than the metabolic expenditure, leads to a consistently reduced amino acid catabolism and to a decreased oxygen consumption, without affecting energy requirements. Although it leads to an increase of carbon dioxide production, the measured change is so small and slow that it is not harmful unless there is severe respiratory insufficiency.