Detection of liver fibrosis with magnetic cross-relaxation

The utility of MRI using magnetization transfer (MT) enhanced pulse sequences to diagnose hepatic cirrhosis in a rat model was investigated. Hepatic T₁ was measured with and without MT off-resonance RF pulses in 17 treated and six control rats. The livers were evaluated histologically, and the hydroxyproline content quantitatively measured. We did not find a statistically significant linear correlation between the MR relaxation times and the degree of tissue injury. However, the MR measurements performed with MT were superior to those without differentiating the treated and control groups. Specifically, the T₁ times were 695 ±76 ms for the treated group, versus 748 ± 61 ms in the controls; P= 0.095. The T_1sat times were also lower in the treated group, with statistical significance: 367 ± 51 ms versus 421 ± 38 ms, P = 0.016. Finally, the change in the relaxation rates (the inverse of the relaxation times) with and without saturation were 1.31 ± 0.22 s^?1 (treated group) versus 1.05 ± 0.12 s^?1 (controls), which differed significantly, P= 0.001.     

Fructose metabolism in the adult mouse optic nerve, a central white matter tract.

Our recent report that fructose supported the metabolism of some, but not all axons, in the adult mouse optic nerve prompted us to investigate in detail fructose metabolism in this tissue, a typical central white matter tract, as these data imply efficient fructose metabolism in the central nervous system (CNS). In artificial cerebrospinal fluid containing 10 mmol/L glucose or 20 mmol/L fructose, the stimulus-evoked compound action potential (CAP) recorded from the optic nerve consisted of three stable peaks. Replacing 10 mmol/L glucose with 10 mmol/L fructose, however, caused delayed loss of the 1st CAP peak (the 2nd and 3rd CAP peaks were unaffected). Glycogen-derived metabolic substrate(s) temporarily sustained the 1st CAP peak in 10 mmol/L fructose, as depletion of tissue glycogen by a prior period of aglycaemia or high-frequency CAP discharge rendered fructose incapable of supporting the 1st CAP peak. Enzyme assays showed the presence of both hexokinase and fructokinase (both of which can phosphorylate fructose) in the optic nerve. In contrast, only hexokinase was expressed in cerebral cortex. Hexokinase in optic nerve had low affinity and low capacity with fructose as substrate, whereas fructokinase displayed high affinity and high capacity for fructose. These findings suggest an explanation for the curious fact that the fast conducting axons comprising the 1st peak of the CAP are not supported in 10 mmol/L fructose medium; these axons probably do not express fructokinase, a requirement for efficient fructose metabolism.     

The Distally Based Sural Artery Flap for Ankle and Foot Coverage

The sural artery flap is a distally based fasciocutaneous flap that has many advantages to offer for coverage in the foot and ankle area. It has the largest arc of rotation of all the regional flaps and does not require sacrifice of any major artery, and moderate-to-large-sized defects can be covered adequately. The dissection technique is simple, and donor site morbidity is minimal. We report our experience with 17 cases. Age range was from 13 to 56 years. Ten (59%) defects were posttraumatic, 3 (17%) were related to reconstructive surgery of the foot or tendon Achilles', 2 (11%) resulted from tumor resection, and 1 each were from infection and gunshot wound. The smallest flap was 6 x 4 cm and the largest was 15 x 12 cm, with the average size being 11 x 7.5 cm. In 5 cases, the donor site was closed primarily, and in other cases, split-thickness skin graft was needed. The short saphenous vein was included in the pedicle in all cases. There was no incidence of complete flap necrosis. Follow-up ranged from 3 to 30 months. Two cases (12%) developed partial superficial necrosis. In 1 case, there was partial wound dehiscence that needed debridement and repair. Another case had postoperative discharge, which subsided after removal of the calcaneal plate. None of the patients complained of any functional problem related to loss of sensation along the lateral border of the foot. The sural island flap is a reliable, safe, and easy method of providing soft tissue coverage in the area of the foot and ankle.     

Synergistic actions of the vitamin D analogue MC 1288 and 15-deoxyspergualin in xenotransplantation

Abstract: The vitamin D analogue MC 1288 (20-epi-1α,25-dihydroxycholecalciferol) effectively postpones rejection of cardiac, intestinal, skin, and aortic allografts. MC 1288 binds to the vitamin D receptor and is thus assumed to exert its immunosuppressive effects via the same mechanisms as 1α,25-dihydroxycholecalciferol, the active form of vitamin D. 1α,25-Dihydroxycholecalciferol has been demonstrated to inhibit the production of various cytokines (interleukin-2, interferon-γ, granulocyte macrophage colony-stimulating factor, and interleukin-12) and to prevent B lymphocyte secretion of immunoglobulins. In the present study MC 1288 was evaluated for its ability to prevent rejection of mouse-to-rat cardiac xenografts, alone and in combination with 15-deoxyspergualin (DSG). Combined treatment with MC 1288 (given days -1 to 9) and DSG (given day -1 and onward) postponed rejection from day 3.0 (untreated recipients) until day 19.5. In rats treated with MC 1288 or DSG as monotherapy, rejection occurred after 3.0 and 7.5 days, respectively. Functioning grafts, obtained on day 9 from recipients treated with MC 1288 and DSG in combination, displayed an almost normal morphology without any obvious deposition of immunoglobulins in the vessels of the grafts and with just a few infiltrating cells. Thus, we have demonstrated synergistic actions of MC 1288 and DSG in delaying rejection of xenografts. Analysis of cellular infiltration, immunoglobulin deposition and graft survival times in the various treatment groups indicate a combined inhibitory effect of these two drugs on the level of macrophage effector function, direct or indirect via T lymphocytes, as well as on antibody production.