Suppression of inward-rectifying K+ channels KAT1 and AKT2 by dominant negative point mutations in the KAT1 alpha-subunit

Na(+)-glucose transport and transepithelial permeability were investigated during symptomatic acute cryptosporidiosis in newborn rats. The infection resulted in a significant (P < 0.01) decrease in the ileal short-circuit current and a nonsignificant fall in the transepithelial potential difference and conductance. In glucose-stimulated conditions, the rise in ileal short-circuit current and transepithelial permeability were significantly lower in Cryptosporidium parvum-infected rats than in controls (delta Isc = 3.24 +/- 1.21 microA.cm-2 vs delta Isc = 5.09 +/- 2.23 microA.cm-2 in infected and control animals, respectively; P < 0.001; delta PD = -0.35 +/- 0.13 mV vs delta PD = -0.44 +/- 0.14 mV for infected and control animals, respectively; P < 0.01). Electrical parameters were not affected by addition of the cyclooxygenase inhibitor indomethacin in either Cryptosporidium-infected newborn rats or controls. Horseradish peroxidase and mannitol flux studies demonstrated a significant decrease (P < 0.05) in transepithelial molecular permeability in infected enterocyte rats, HRP flux = 380, range 68-5570 ng.cm-2, and mannitol flux = 1.06, range, 0.34-1.44%.cm-2.min-1, compared with controls rats, HRP flux = 4446 range, 1121-124,363 ng.cm-2, and mannitol flux = 1.99, range, 0.57-5.09%.cm-2.min-1; P < 0.05. These effects could originate from C. parvum-induced alteration of intracellular trafficking of pinocytosis vesicles and therefore account for the decrease in permeability to solute and macromolecules, together with impaired transcellular nutrient transport, in suckling rats.     

Magnetic resonance imaging with implanted neurostimulators: an in vitro and in vivo study

OBJECTIVE: The goal was to assess the safety of magnetic resonance imaging (MRI) with implanted neurostimulators, in an in vitro and in vivo study. METHODS: Two different implantable pulse generators (IPGs) (ITREL II and 3; Medtronic, Minneapolis, MN) and different leads (separately and connected to an IPG) were tested in three different MRI scanners (0.2, 0.25, and 1.5 T). Measurements of the induced voltages (using an external oscilloscope) and the induced heat (using an infrared camera) were performed in an in vitro study. Finally, 38 patients with implanted neurostimulator systems (leads and IPGs) underwent MRI in 50 examinations, with continuous monitoring by a physician with uninterrupted visual and vocal contact with the patient. Twenty-five patients were studied prospectively, with documented printouts of the parameter settings before and after MRI. RESULTS: An induced voltage of 2.4 to 5.5 V was measured in the experimental configuration with a lead connected to an IPG. The voltage was higher with the leads alone, compared with the leads connected to the IPG, and was dependent on the MRI scanner, the sequences, and the type of lead. No heat induction was observed in any part of the hardware. No change of pulse shape or change of IPG parameters was observed during MRI. No adverse effects occurred in patients with chronically implanted deep brain leads connected to an IPG. CONCLUSION: MRI can be safely performed in patients with implanted neurostimulation systems with the tested deep brain leads connected to an IPG (ITREL II and 3), with running parameters. No heat induction was detected, and the experimentally measured induced voltage did not seem to harm the patients. Only the reed switch of the IPGs was activated; the other parameters remained unchanged. Further investigations must be performed to study the local electrical effects in larger plate electrodes; these effects might cause slight discomfort. There is no danger with any type of electrode during MRI examinations if the electrodes lie outside the region of interest. These observations are restricted to the tested devices. A conscientious estimation of the risks and benefits of MRI for patients with implanted devices is recommended. If the type of device is not known to the examiner, MRI should still be considered to be contraindicated.     

Optimal Strategies for a Semi-Markovian Inventory System

Control for a semi-Markovian inventory system is considered. Under general assumptions on system functioning, conditions for existence of an optimal nonrandomized Markovian strategy are found. It is shown that under some additional assumptions on storing conditions for the inventory, the optimal strategy has a threshold (s, S)-frame.     

Granulocytic sarcoma presented as a reactivation of chronic myeloid leukemia after allogenic marrow transplantation

The authors report the case of a chronic myeloid leukemia (CML) patient submitted to allogenic bone marrow transplantation, who had probably never entered complete remission. The disease was reactivated as a granulocytic sarcoma, next to a platinum plate installed to correct a tibia fracture 11 years earlier. Its final event was a myeloid Ph1 + blastic crisis that was unsuccessfully treated with high doses of sc interferon and citarabine.     

Synthesis and pharmacological evaluation of 1-methyl-5-[substituted-4 (3H)-oxo-1,2,3-benzotriazin-3-yl]-1H-pyrazole-4-acetic acid derivatives

Several new 1-methyl-5-[substituted-4-oxo-1,2,3-benzotriazin-3-yl] -1H-pyrazole-4-acetic acids and their ethyl ester derivatives were prepared. The compounds were tested for analgesic and antiinflammatory activities, acute toxicity, ulcerogenic effect, and as in vitro inhibitors of 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), since it is claimed that the inhibition of such an enzyme predicts in vivo antiinflammatory activity. Some compounds were more active than phenylbutazone in the phenylbenzoquinone and acetic acid peritonitis tests, and equiactive to the same drug in the carrageenin paw edema test. All the compounds inhibited the 3 alpha-HSD, but no correlation was observed with the paw edema inhibition values. The compounds proved to possess marginal or no ulcerogenic effect, as well as low systemic toxicity.     

Refinement of technique for cosmonaut's body radiation loading estimation using of orbital station dosimetric monitoring system

Proposed is a technique for estimation of radiation loading of cosmonauts' body from the data of the space station radiation monitoring system by bringing the objective to a linear mathematical model. Resulted matrix ratios allow to work out the challenge; test calculations illustrating efficiency of the proposed technique are included.