Vacuum laser acceleration of super-ponderomotive electrons using relativistic transparency injection.

Intense lasers can accelerate electrons to very high energy over a short distance. Such compact accelerators have several potential applications including fast ignition, high energy physics, and radiography. Among the various schemes of laser-based electron acceleration, vacuum laser acceleration has the merits of super-high acceleration gradient and great simplicity. Yet its realization has been difficult because injecting free electrons into the fast-oscillating laser field is not trivial. Here we demonstrate free-electron injection and subsequent vacuum laser acceleration of electrons up to 20 MeV using the relativistic transparency effect. When a high-contrast intense laser drives a thin solid foil, electrons from the dense opaque plasma are first accelerated to near-light speed by the standing laser wave in front of the solid foil and subsequently injected into the transmitted laser field as the opaque plasma becomes relativistically transparent. It is possible to further optimize the electron injection/acceleration by manipulating the laser polarization, incident angle, and temporal pulse shaping. Our result also sheds light on the fundamental relativistic transparency process, crucial for producing secondary particle and light sources.

Neuroprotection from delayed postischemic administration of a metalloporphyrin catalytic antioxidant.

Reactive oxygen species contribute to ischemic brain injury. This study examined whether the porphyrin catalytic antioxidant manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) reduces oxidative stress and improves outcome from experimental cerebral ischemia. Rats that were subjected to 90 min focal ischemia and 7 d recovery were given MnTE-2-PyP(5+) (or vehicle) intracerebroventricularly 60 min before ischemia, or 5 or 90 min or 6 or 12 hr after reperfusion. Biomarkers of brain oxidative stress were measured at 4 hr after postischemic treatment (5 min or 6 hr). MnTE-2-PyP(5+), given 60 min before ischemia, improved neurologic scores and reduced total infarct size by 70%. MnTE-2-PyP(5+), given 5 or 90 min after reperfusion, reduced infarct size by 70-77% and had no effect on temperature. MnTE-2-PyP(5+) treatment 6 hr after ischemia reduced total infarct volume by 54% (vehicle, 131 +/- 60 mm(3); MnTE-2-PyP(5+), 300 ng, 60 +/- 68 mm(3)). Protection was observed in both cortex and caudoputamen, and neurologic scores were improved. No MnTE-2-PyP(5+) effect was observed if it was given 12 hr after ischemia. MnTE-2-PyP(5+) prevented mitochondrial aconitase inactivation and reduced 8-hydroxy-2'-deoxyguanosine formation when it was given 5 min or 6 hr after ischemia. In mice, MnTE-2-PyP(5+) reduced infarct size and improved neurologic scores when it was given intravenously 5 min after ischemia. There was no effect of 150 or 300 ng of MnTE-2-PyP(5+) pretreatment on selective neuronal necrosis resulting from 10 min forebrain ischemia and 5 d recovery in rats. Administration of a metalloporphyrin catalytic antioxidant had marked neuroprotective effects against focal ischemic insults when it was given up to 6 hr after ischemia. This was associated with decreased postischemic superoxide-mediated oxidative stress.

5-HT3 agonist-induced dopamine overflow during withdrawal from continuous or intermittent cocaine administration.

This experiment examined alterations in the ability of the highly selective 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide (mCPBG), to induce dopamine (DA) overflow in caudate brain slices obtained from rats withdrawn from continuous or intermittent cocaine administration. Rats were pretreated with 40 mg/kg per day cocaine for 14 days by either subcutaneous injections or osmotic minipumps, and then withdrawn from this regimen for 7 days. Caudate brain slices were obtained, and perfused with artificial cerebrospinal fluid. Following an equilibration period, the slices were then perfused with 25, 50, or 100 microM mCPBG. The samples were assayed for DA content by HPLC with electrochemical detection. The results indicated that the pretreatment with intermittent cocaine did not consistently alter the ability of mCPBG to induce DA overflow, although there was a reduction in the amount of DA released by the highest concentration of mCPBG. In contrast, pretreatment with continuous cocaine administration consistently and significantly attenuated the ability of mCPBG to induce DA overflow. The DA overflow induced by mCPBG was partially dependent on extracellular Ca2+ in the perfusion medium for the saline control and intermittent administration subjects: elimination of Ca2+ from the medium significantly reduced, but did not eliminate, DA overflow for these two groups. In contrast, elimination of Ca2+ from the perfusion medium had a significant enhancing effect on mCPBG-induced DA overflow in the continuous administration rats. These results suggest that distinct temporal patterns of cocaine administration differentially alter the ability of a 5-HT3 agonist to increase extracellular DA levels, and that this effect may be related to an impairment of Ca(2+)-dependent release.(ABSTRACT TRUNCATED AT 250 WORDS)

Subfractionation of human very low density lipoproteins by heparin-Sepharose affinity chromatography.

Very low density lipoproteins obtained from normolipidemic subjects were fractionated into subclasses by means of affinity chromatography on a heparin-Sepharose column in the presence of MnCl2. The four subfractions eluted at 0.05, 0.12, 0.20, and 0.38 M NaCl and they differed in chemical composition and apoprotein pattern. The relative amounts of apoB and apoE in subfractions increased with increasing concentrations of the NaCl eluant. Modification of the arginyl residues with 1-2 cyclohexadione demonstrated that arginine plays an important role in determining the elution pattern of VLDL. In vitro studies indicated that only fractions eluted at 0.2 and 0.5 M NaCl compete with LDL for cellular receptors. These data suggest that the various subfractions may represent VLDL at different stages of catabolism.

Diabetic nephropathy: from micro- to macroalbuminuria.

This brief review will focus on the major factors leading to incipient diabetic nephropathy (i.e. microalbuminuria) progressing to overt nephropathy (i.e. macroalbuminuria) and particularly on the role of glycaemic control and hypertension. Both experimental and cohort studies support the role of hyperglycaemia in the development of diabetic nephropathy. Some recent long-term interventional studies in microalbuminuric patients show conflicting results regarding the role played by good metabolic control in reducing the incidence of overt nephropathy. However, strict metabolic control, which is fundamental in normoalbuminuric patients, is of little use even in microalbuminuric patients. In general, levels of glycosylated haemoglobin less than two standard deviations above the upper normal range, commonly <7.5-8%, seem to protect patients from developing nephropathy. The results of many cross-sectional studies have shown that the progression of renal damage regularly is accompanied by arterial hypertension both in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Many long-term interventional studies have been performed in order to understand the effect of antihypertensive treatment on the incidence of proteinuria in both normotensive and hypertensive patients with IDDM or NIDDM. These data show a marked effect of antihypertensive therapy in preventing the onset of overt nephropathy, and suggest the superiority of angiotensin-converting enzyme (ACE) inhibitors. We believe that optimal blood pressure values are approximately 120/70-75 mmHg in younger patients and 125-130/80-85 mmHg in older patients. In conclusion, antihypertensive treatment, ACE inhibitors per se and possibly strict metabolic control reduce the development of nephropathy, thus playing a striking role in the secondary prevention of renal failure.

Intrarenal arteriosclerosis and impairment of kidney function in NIDDM subjects.

It is currently under debate whether the pathogenesis of end-stage renal failure in non-insulin-dependent diabetes mellitus (NIDDM) is a consequence of microangiopathy alone. The aim of this study was to investigate intrarenal arteriosclerosis and its correlation with kidney function in NIDDM. In 36 diabetic subjects, and in 10 age- and sex-matched healthy control subjects we measured kidney volume and resistive index of the interlobar arteries by duplex Doppler ultrasonography. Clinical and metabolic parameters, renal function and vascular sequelae of the disease were also evaluated. In diabetic subjects resistive index (median 0.72, range 0.54-0.79) was higher than in control subjects (median 0.62, range 0.57-0.66) (2p < 0.002). Kidney volume and resistive index correlated with age (p < 0.004), body mass index (p < 0.001), mean blood pressure (p < 0.001), total and LDL cholesterol (p < 0.01) and creatinine clearance (p < 0.001 and < 0.01, respectively). Kidney volume also correlated with HbA1 (p < 0.01) and resistive index with uric acid (p < 0.01). Lower body macroangiopathy was associated with increased resistive index and reduced kidney volume (2p < 0.05), while upper body macroangiopathy and microangiopathy were not. Our data suggest that macroangiopathy rather than microangiopathy is mainly responsible for impairment of kidney function in NIDDM. The resistive index of interlobar arteries seems to be a reliable marker of intrarenal arteriosclerosis and can be used as a non-invasive, easily available parameter of its evolution.