Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.     

Acute transverse myelitis in the emergency department: A case report and review of the literature

Acute transverse myelitis (ATM) is a neurologic condition that presents with bilateral lower extremity weakness and sensory loss associated with bowel and bladder dysfunction. Whereas the time of onset may be hours to days, the time to either partial or complete recovery may require months. The etiology is varied and may be idiopathic. Laboratory and radiographic evaluation may be nonrevealing. Corticosteriods have been used for treatment, but their efficacy is controversial. As illustrated by this case report, the essential aspect of the initial management of ATM is the elimination of potentially treatable causes.     

Metabolic and hemodynamic responses to concurrent voluntary arm crank and electrical stimulation leg cycle exercise in quadriplegics.

This study determined the metabolic and hemodynamic responses in eight spinal cord injured (SCI) quadriplegics (C5-C8/T1) performing subpeak arm crank exercise (ACE) alone, subpeak functional electrical stimulation leg cycle exercise (FES-LCE) alone, and subpeak FES-LCE concurrent with subpeak ACE (hybrid exercise). Subjects completed 10 minutes of each exercise mode during which steady-state oxygen uptake (VO2), pulmonary ventilation (VE), heart rate (HR), cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), arteriovenous oxygen difference (a-v O2 diff), and total peripheral resistance (TPR) were determined. Although mean VO2 for both ACE alone and FES-LCE alone was matched at 0.66 l/mi, individualized power outputs ranged from 0-30 W (mean = 19.4 +/- 1.3) and 0-12.2 W (mean = 2.3 +/- 0.6), respectively. Hybrid exercise elicited significantly higher VO2 (by 54 percent), VE (by 39-53 percent), HR (by 19-33 percent), and CO (by 33-47 percent), and significantly lower TPR (by 21-34 percent) than ACE or FES-LCE performed alone (P less than or equal to 0.05). Stroke volume was similar between hybrid exercise and FES-LCE alone, and these two exercise modes evoked a significantly higher SV (by 41-56 percent) than during ACE alone. These data clearly demonstrate that hybrid exercise creates a higher aerobic metabolic demand and cardiac-volume load in SCI quadriplegics than either subpeak levels of ACE or FES-LCE performed separately. Therefore, hybrid exercise may provide more advantageous central cardiovascular training effects in quadriplegics than either ACE or FES-LCE alone.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.      

Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis.

Axon outgrowth during development and neurotransmitter release depends on exocytotic mechanisms, although what protein machinery is common to or differentiates these processes remains unclear. Here we show that the neural t-SNARE (target-membrane-associated-soluble N-ethylmaleimide fusion protein attachment protein (SNAP) receptor) SNAP-25 is not required for nerve growth or stimulus-independent neurotransmitter release, but is essential for evoked synaptic transmission at neuromuscular junctions and central synapses. These results demonstrate that the development of neurotransmission requires the recruitment of a specialized SNARE core complex to meet the demands of regulated exocytosis.     

新疆家畜蠕形蚤病病原研究

本文详细介绍了在新疆发现的花蠕形蚤、叶氏蠕形蚤、北山羊蠕形蚤、羊长喙蚤和狍长喙蚤的形态学特点、地理分布和某些生物学特性。     

Splenic abscess and peritonitis in a continuous ambulatory peritoneal dialysis (CAPD) patient

A 26-year-old female was on continuous ambulatory peritoneal dialysis (CAPD) because of diabetic end-stage renal failure. She developed an acute peritonitis that relapsed repeatedly despite appropriate antibiotic treatment. Investigations showed the presence of a splenic abscess, and splenectomy and peritoneal cannula removal were required. The patient died of myocardial infarction two weeks postoperatively. This is the first recorded case of peritonitis secondary to splenic abscess in a CAPD patient. Autopsy findings suggest that the abscess developed from infection of a splenic infarct.