A new mechanism for the formation of meteoritic kerogen-like material.

The carbon in ancient carbonaceous chondritic meteorites is mainly in a hydrocarbon composite similar to terrestrial kerogen, a cross-linked structure of aliphatic and aromatic hydrocarbons. Until recently, the composite has been commonly thought to have been produced in the early solar nebula by a Fischer-Tropsch-type process, involving the catalytic synthesis of hydrocarbons from carbon monoxide and hydrogen on grain surfaces. Instead, the aromatic hydrocarbons may form in gas-phase pyrolysis of simple aliphatics like acetylene and methane by a mechanism developed recently to explain formation of soot in combustion and of aromatic molecules in circumstellar envelopes. Nonequilibrium chemical kinetic calculations indicate that this mechanism can produce meteoritic aromatics if the initial concentration of simple hydrocarbons in the solar nebula was sufficiently but not unreasonably high.

Ion Velocity Measurements for the Ionospheric Connections Explorer.

The Ionospheric Connections Explorer (ICON) payload includes an Ion Velocity Meter (IVM) to provide measurements of the ion drift motions, density, temperature and major ion composition at the satellite altitude near 575 km. The primary measurement goal for the IVM is to provide the meridional ion drift perpendicular to the magnetic meridian with an accuracy of 7.5 ms-1 for all daytime conditions encountered by the spacecraft within 15° of the magnetic equator. The IVM will derive this parameter utilizing two sensors, a retarding potential analyzer (RPA) and an ion drift meter (IDM) that have a robust and successful flight heritage. The IVM described here incorporates improvements in the design and operation to produce the most sensitive device that has been fielded to date. It will specify the ion drift vector, from which the component perpendicular to the magnetic field will be derived. In addition it will specify the total ion density, the ion temperature and the fractional ion composition. These data will be used in conjunction with measurements from the other ICON instruments to uncover the important connections between the dynamics of the neutral atmosphere and the ionosphere through the generation of dynamo currents perpendicular to the magnetic field and collisional forces parallel to the magnetic field. Here the configuration and operation of the IVM instrument are described as well as the procedures by which the ion drift velocity is determined. A description of the subsystem characteristics, which allow a determination of the expected uncertainties in the derived parameters, is also given.

A comparison of fish oil or corn oil supplements in hyperlipidemic subjects with NIDDM.

OBJECTIVE: To examine the effects on blood lipids and glycemic control of fish oil and corn oil supplementation at two levels in subjects with hyperlipidemia and non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Forty subjects (18 men and 22 women; aged 53.9 +/- 7.0 years) with NIDDM and hyperlipidemia were randomly assigned to one of four treatment groups: 9 g of fish oil, 18 g of fish oil, 9 g of corn oil, or 18 g of corn oil daily supplementation for 12 weeks. RESULTS: The level of oil supplements (9 g compared with 18 g) did not have a significant effect within each oil group on glycemic control and lipids. Significant differences (P < 0.05) in lipids were found when the 9-g and 18-g groups were combined. In subjects consuming fish oil, plasma very-low-density lipoprotein (VLDL) cholesterol (P = 0.0001), plasma triglyceride (TG) (P = 0.0001), and plasma VLDL TGs (P = 0.02 at 6 weeks and P = 0.0001 at 12 weeks) were significantly lowered compared with subjects consuming corn oil. Plasma VLDL cholesterol increased across time in the corn oil group (P = 0.04). Plasma low-density lipoprotein (LDL) cholesterol was temporarily increased (P = 0.008) in the fish oil group at 6 weeks, but the effect was no longer present at 12 weeks. No significant differences between fish oil- or corn oil-supplemented diets were found in total plasma cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, glycosylated HbA1c, weight, and blood pressure. CONCLUSIONS: In this study, fish oil supplementation improved plasma VLDL cholesterol, VLDL TGs, and total TGs while having a transient deterioration in LDL cholesterol in subjects with NIDDM. Furthermore, fish oil supplementation had no significant deleterious effect on glycemic control.

Extracellular Na+ removal enhances granule secretion in platelets--evidence that Na+/H+ exchange is inhibitory to secretion induced by some agonists.

The effect of extracellular Na+ [( Na+]e) removal on agonist-induced granule secretion in platelets in relation to [pH]i and [Ca2+]i changes was investigated. Substitution of [Na+]e with choline+ of K+ resulted in a significant enhancement of 5HT secretion induced by thrombin, collagen, U46619 and the protein kinase C activators, PMA and diC8. Increases in [Ca2+]i induced by thrombin and U46619 were slightly inhibited or unaffected in these buffers, but [pH]i increases induced by thrombin, U46619, PMA and diC8 were abolished and a drop in [pH]i (0.05 0.1 units below resting) was observed. Although preincubation with potassium acetate produced a big drop in [pH]i and greatly increased secretion with all the agonists, particularly in the absence of [Na+]e, clear evidence that [pH]i rises due to Na+/H+ exchange are inhibitory to secretion was obtained only with thrombin. Thus, (i) NH4Cl, which restored the increase in [pH]i in the absence of [Na+]e reduced the potentiated secretory response to thrombin, (ii) no increase in thrombin-induced secretion was observed when Na+ was replaced with Li+, which allowed a normal increase in [pH]i and (iii) ethyl isopropyl amiloride (EIPA) abolished the [pH]i rise and potentiated thrombin-induced secretion. With collagen and U46619, the results suggest that removal of [Na+]e per se rather than inhibition of Na+/H+ exchange results in enhanced secretion. It is concluded that [Na+]e per se and [pH]i elevations via Na+/H+ exchange both have important inhibitory roles in the control of platelet granule secretion.

Na+/H+ exchange is not necessary for protein kinase C-mediated effects in platelets.

The role of Na+/H+ exchange in protein kinase C-mediated effects in platelets was investigated by studying the effect of removal of extracellular Na+ ([Na+]e) on the different responses induced by phorbol 12-myristate 13-acetate (PMA) and 1,2-dioctanoylglycerol (diC8). None of the responses studied, namely, protein phosphorylation, translocation of enzyme activity to the membrane fraction, potentiatory and inhibitory effect on platelet activation ([Ca2+]i, arachidonate and granule release) showed an absolute dependence on [Na+]e. With the exception of dense-granule release, which was clearly potentiated by the removal of [Na+]e and showed a negative correlation with exchanger activity, the other effects of PMA and diC8 were not affected by [Na+]e removal. It is concluded that Na+/H+ exchange is not essential for protein kinase C activation in platelets.

SPECT quantification of cerebral ischemia before and after carotid endarterectomy.

A method to assess changes in cerebral perfusion following carotid endarterectomy was developed using late (2 hr)/early (20 min) single-photon emission computed tomography (SPECT)/[123I]iodoamphetamine count ratios. Using a ratio greater than 1.0 to indicate redistribution and reversible ischemia, pre- and postoperative studies were compared for 20 patients. Regional polar plots based on 30 degrees angular sectors showed improvement greater than 2 standard deviations (s.d.s) ipsilateral to surgery in 15/19 (79%) and contralateral to the side of surgery in 8/19 (42%) patients with significant hemodynamic lesions. Using a hemispheric perfusion index (mean of four 30 degrees sectors) ipsilateral perfusion improved in 11/19 (58%) with bilateral improvement in 6/19 (32%). Visual interpretation was similar to the regional analysis with 14/19 (74%) improving on the operative side; however, it was less sensitive for contralateral changes, 4/19 (21%). We conclude that quantitation of redistribution can provide an objective index of improved perfusion and is especially important to detect contralateral changes.

Pyridine nucleotide hydrolysis and interconversion in rat hepatocytes during oxidative stress.

A characteristic feature of many types of chemically induced oxidative stress is a depletion of the pyridine nucleotide NAD+. This has been attributed to either its hydrolysis to nicotinamide and ADP-ribose or to its phosphorylation (interconversion) to NADP+. In this study the exposure of rat hepatocytes to either tert-butyl hydroperoxide (250-750 microM) or 2,3-dimethoxy-1,4-naphthoquinone (50 microM) resulted in a rapid depletion of NAD+ with no change in the level of NAD. The depletion of NAD+ was accompanied by an increase in nicotinamide. The rate of NAD+ deletion induced by tert-butyl hydroperoxide (500 microM) and 2,3-dimethoxy-1,4-naphthoquinone (50 microM) was reduced by preincubating the hepatocytes for 1 hr with either 3-aminobenzamide (20 mM), nicotinamide (10 mM) or theophylline (7.5 mM), potent inhibitors of poly(ADP-ribose)polymerase. In cells exposed to 2,3-dimethoxy-1,4-naphthoquinone (50 microM) extensive oxidation of NADPH to NADP+ was observed; this was followed by an increase in the level of NADP(+) + NADPH (NADP(H)). However, no change in the total pyridine nucleotide (NAD(H) + NADP(H)) pool was detected. Exposure to tert-butyl hydroperoxide resulted in the oxidation of NADPH to NADP+ and a decrease in total pyridine nucleotide pool. These results suggest that during oxidative stress, NAD+ is hydrolysed to nicotinamide, possibly by the activation of poly(ADP-ribose)polymerase and that the depletion of NAD+ is independent of the increase in NADP+. Furthermore, no evidence of an interconversion of NAD+ to NADP+ was found.

Quinone-induced DNA single strand breaks in rat hepatocytes and human chronic myelogenous leukaemic K562 cells.

In rat hepatocytes exposed to the quinones menadione and 2,3-dimethoxy-1,4-naphthoquinone (2,3-diOMe-1,4-NQ) a decrease in NAD+ is observed. DNA damage and activation of poly(ADP-ribose)polymerase are often associated with a decrease in NAD+. Using rat hepatocytes and human myeloid leukaemic cells (K562), we examined the extent of DNA damage induced by these quinones at non-toxic concentrations, i.e. at concentrations at which the cells completely exclude the dye trypan blue. Both quinones caused significant DNA damage at very low concentrations (5-100 microM). With 2,3-diOME-1,4-NQ (15 microM) or menadione (15 microM) single strand breaks (SSB) were observed at very early time points (less than 5 min), reaching a maximum between 20 and 30 min. Most SSB were repaired within 45 min of the removal of the quinones. Whilst extensive repair was observed within 4 hr of the removal of 2,3-diOMe-1,4-NQ (15 microM), only partial repair was observed following exposure to menadione (15 microM). SSB induced by 2,3-diOMe-1,4-NQ (15 microM) were completely inhibited by the iron chelator 1,10-phenanthroline (25 microM), whereas in cells exposed to menadione (15 microM) they were only partially inhibited. Finally, although the membrane integrity of K562 cells was unaffected by exposure to high concentrations of both quinones (less than or equal to 400 microM), cytostasis was observed at much lower concentrations (50 microM). Our results demonstrate that at very low concentrations these quinones induce extensive DNA damage possibly caused by hydroxyl radicals. The DNA damage was accompanied by an early cytostasis but no loss of membrane integrity.

Cat-scratch disease simulating Histiocytosis X.

Cat-scratch disease is a self-limited condition commonly causing a benign chronic lymphadenopathy in children. Osteolytic lesions are a rare complication, but have been previously reported. We report a case of a solitary osteolytic lesion of the skull whose clinical, radiographic and pathological features were initially interpreted as being consistent with Histiocytosis X. Subsequently, positive serological titers for Bartonella, a history of a cat-scratch antecedent to the onset of clinical symptoms and review of the original histopathology confirmed the diagnosis of cat-scratch disease. We reviewed the English language literature on osteolytic lesions associated with cat-scratch disease and compare the current case with those previously reported.

Methapyrilene hepatotoxicity is associated with oxidative stress, mitochondrial disfunction and is prevented by the Ca2+ channel blocker verapamil.

Methapyrilene (MP) is an unusual hepatotoxin in that it causes periportal necrosis in rats. The mechanism of acute methapyrilene hepatotoxicity has, therefore, been investigated in cultured male rat hepatocytes. Addition of methapyrilene to rat hepatocytes resulted in a time- and dose-dependent loss in cell viability between 4 and 8 h of incubation as judged by cellular enzyme leakage. The cytochrome P450 (CYP) inhibitor metyrapone protected against methapyrilene-mediated toxicity suggesting that MP is metabolised by CYP for toxicity. The concentration-dependent protection from methapyrilene toxicity afforded by metyrapone correlated with an inhibition of microsomal CYP2C11-associated androstenedione 16alpha hydroxylase activity, and hepatocytes prepared from hypophysectomised rats (containing reduced levels of microsomal immunodetectable CYP2C11 and associated androstenedione 16alpha hydroxylase activity) showed resistance to the toxic effects of methapyrilene. These data suggest that the toxicity of methapyrilene is predominantly dependent on the CYP2C11 isoform. Treatment of hepatocytes with a toxic concentration of MP caused oxidative stress as indicated by increases in NADP+ levels within 2 h and cellular thiol oxidation as evidenced by a reduction--but not complete loss--in glutathione levels. Methapyrilene hepatotoxicity was associated with an early loss in mitochondrial function, as indicated by mitochondrial swelling and significant losses in cellular ATP within 2 h. Co-incubation of methapyrilene-treated hepatocytes with inhibitors of inner mitochondrial transition permeability pore opening--cyclosporin A or the thiol reductant dithiothreitol--abrogated cell death suggesting that pore opening and loss of mitochondrial Ca2+ homeostasis play a significant role in methapyrilene-mediated cell death. Co-incubation of methapyrilene-treated hepatocytes with the phenylalkylamine calcium channel blocker verapamil--but not by treating cells in a nominally calcium-free medium--also abrogated cell death, suggesting that if Ca2+ is involved in cell killing then it is dependent on an intracellular Ca2+ pool. Pre-treatment of hepatocytes for 1 h with verapamil--to inhibit intracellular Ca2+ pool filling--increased the potency of verapamil protection against methapyrilene toxicity by approximately 100-fold. Taken together, these data indicate that methapyrilene intoxication leads to mitochondrial disfunction and suggest a critical role for a loss of mitochondrial Ca2+ homeostasis in this model of hepatocyte death.

Pecans lower low-density lipoprotein cholesterol in people with normal lipid levels.

OBJECTIVE: To compare serum lipid profiles and dietary intakes of people with normal lipid levels who consumed pecans and those who did not consume nuts. DESIGN: Eight-week, randomized, controlled study of pecan treatment group vs control group. SUBJECT: Nineteen people with normal lipid levels completed the study; 10 had been randomly assigned to the pecan treatment group (7 women, 3 men, mean age = 45 +/- 10 years) and 9 to the control group (8 women, 1 man, mean age = 37 +/- 12 years). INTERVENTION: The pecan treatment group consumed 68 g pecans per day for 8 weeks plus self-selected diets. The pecans contributed 459 kcal and 44 g fat daily. The control group avoided nuts and consumed self-selected diets. MAIN OUTCOME MEASURES: Total serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total triglyceride levels were measured at the time of entrance to the study (baseline), week 4, and week 8. Computer analyses were done on five 3-day food records. STATISTICAL ANALYSIS: Comparisons were made using analysis of variance or paired t test. RESULTS: LDL-C was lowered in the pecan treatment group from 2.61 +/- 0.49 mmol/L at baseline to 2.35 +/- 0.49 at week 4 (P < .05) and to 2.46 +/- 0.59 at week 8 (P < .05). At week 8, total cholesterol and HDL-C in the pecan treatment group were significantly lower (P < .05) than in the control group (total cholesterol: 4.22 +/- 0.83 vs 5.02 +/- 0.54 mmol/L; HDL-C: 1.37 +/- 0.23 vs 1.47 +/- 0.34 mmol/L). Dietary fat, monounsaturated fat, polyunsaturated fat, insoluble fiber, magnesium, and energy were significantly higher in the pecan treatment group than in the control group. Body mass indexes and body weights were unchanged in both groups. APPLICATIONS: Pecans can be included in a healthful diet when energy intake and potential weight gain are addressed.

The role of reactive oxygen species in adriamycin and menadione-induced glomerular toxicity.

Redox cycling leading to oxidative stress has been proposed as the mechanism by which adriamycin induces glomerular toxicity in rats. The present study compares the extent of the oxidative stress and cytotoxicity induced by adriamycin to menadione (a model redox cycling quinone) in freshly isolated rat glomeruli. Adriamycin and menadione (25 microM) decreased de novo protein synthesis (measured by 3H-proline incorporation into acid-precipitable glomerular protein) by 50 and 85%, respectively, in 2 h. By contrast, menadione at 25 microM reduce glomerular membrane integrity (as assessed by lactate dehydrogenase leakage), adriamycin reduced membrane integrity at 500 microM adriamycin. Reactive oxygen species (ROS) were measured by the oxidation of dihydrodichlorofluorescein. Menadione (25 microM) and adriamycin (25 microM) increased ROS formation to 260 and 156% of controls after 30 min incubation, respectively. Oxidative stress was assessed by measuring the intracellular level of reduced glutathione (GSH) and the decrease of the NADPH/NADP- ratio which stimulates the pentose phosphate pathway (PPP): (a) menadione (25-100 microM) reduced glomerular GSH to 10-20% of controls, adriamycin (25-100 microM) had no effect; (b) menadione (10 microM) increased PPP activity 6-fold, while adriamycin (125 microM) had only a 2-fold effect. Although adriamycin and menadione generate extensive ROS and decrease protein synthesis, there was no correlation between the extent of oxidative stress and cytotoxicity in glomeruli exposed to adriamycin. These results suggest that oxidative stress may not be the primary mechanisms by which adriamycin induces selective glomerular toxicity.

The role of ursodeoxycholic acid in bile acid-mediated kidney fragment toxicity.

Elevated levels of bile acids are thought to play an important role in the renal failure of patients with obstructive jaundice undergoing surgery. In contrast, ursodeoxycholic acid (UDA) is widely used to improve cholestasis and has been proposed as protective bile acids and antioxidant. The present study employs kidney fragments to determine the role of reactive oxygen species (ROS) in the mechanism of toxicity of hydrophobic bile acids and to determine the nephroprotectant properties of UDA against the hydrophobic bile acids. The hydrophobic bile acids chenodeoxycholic (200 microM) and deoxycholic acid (200 microM) significantly (P<0.05) increased lactate dehydrogenase leakage (LDH) from glomerular fragments from 2.7+/-0.4 to 5.03+/-0.23 and 4.66+/-0.37 (micromol NADH consumed/min/mg protein) for chenodeoxycholic and deoxycholic acid respectively. Preincubating the fragments with UDA (500 microM) did not prevent the leakage of LDH caused by the bile acids. The level of lipid peroxidation was not increased in fragments exposed to either ursodeoxycholic (0-500 microM), lithocholic (0-100 microM), chenodeoxycholic (0-500 microM) or deoxycholic acid (0-500 microM). Furthermore UDA (500 microM) did not prevent the increase in lipid peroxidation caused by tert-butyl hydroperoxide (0-1000 microM) in the fragments. These results suggest that hydrophobic bile acids do not cause lipid peroxidation in kidney fragments and that UDA is neither capable of preventing the loss of membrane integrity induced by hydrophobic bile acids or acting as an antioxidant in kidney fragments.

The Army dietitian in Panama: military hospital feeding and humanitarian efforts during Operation Just Cause.

The delivery of nutrition during a military conflict creates added demands on food service operations. Dietitians in the United States Army assisted the civilian population in Panama by participating in humanitarian feeding efforts during Operation Just Cause from December 1989 to January 1990. They provided hospital nutrition under combat conditions and assisted in a displaced-persons camp by developing an Emergency Food Plan that incorporated indigenous foods. The Army Medical Specialist Corps instituted training programs to prepare Army dietitians for refugee feeding in the post-Cold War era as a result of the lessons learned during this and other humanitarian efforts.

Using State Board of Nursing data to estimate the number of nurse practitioners in the United States.

Knowing the number of nurse practitioners, both at the state and national levels, is important to those dealing with health care policy and education. To determine these numbers, we telephoned all state boards of nursing, and asked whether they distinguished nurse practitioners from other registered nurses and what the respective numbers were. Data were available from a time period beginning in March 1992 and ending in September 1992. Thirty-four states, representing 70.6 percent of all registered nurses, now distinguish nurse practitioners from other nurses. In these states, 1.35 percent of all registered nurses are nurse practitioners. Projecting this percentage to the states that do not make the distinction yields a total of 33,834 nurse practitioners in the United States. Using neighboring states rather than the national average as a predictor for no-data states leads to a national total estimate of 31,294. When corrected for multistate licensure, the final estimated number is 27,226. This estimating method should yield even more accurate data in the future as more states certify and list their nurse practitioners. This method enumerates nurse practitioners as defined by the various states, which have highly variable definitions of what a nurse practitioner is. However, the variability in legal definition is decreasing as more states require national certification.

The clinical education of primary care nurse practitioner students.

Directors of 112 ambulatory care nurse practitioner (NP) programs were surveyed to determine the amount and characteristics of the clinical education of their students. The response rate was 53%. Among all programs, students experienced an average of 597 clinical hours. This number was somewhat higher among family and women's health nurse practitioner programs. The range was large--192 to 1600 hours--however, eliminating both extremes left a majority of programs within a much narrower range; the central 62% of programs were between 400 and 700 hours. Certificate programs reported more hours than did masters programs. Almost all hours were in ambulatory settings, which included a wide mixture of public and private settings. A majority of students experience part of their clinical training along with medical residents and medical students, and often with NP students from other programs and with physician assistant students. Most NP program directors find these other disciplines' programs cooperative, and the NP directors favor stronger relationships.