Probing the core of the strong nuclear interaction.

The strong nuclear interaction between nucleons (protons and neutrons) is the effective force that holds the atomic nucleus together. This force stems from fundamental interactions between quarks and gluons (the constituents of nucleons) that are described by the equations of quantum chromodynamics. However, as these equations cannot be solved directly, nuclear interactions are described using simplified models, which are well constrained at typical inter-nucleon distances1-5 but not at shorter distances. This limits our ability to describe high-density nuclear matter such as that in the cores of neutron stars6. Here we use high-energy electron scattering measurements that isolate nucleon pairs in short-distance, high-momentum configurations7-9, accessing a kinematical regime that has not been previously explored by experiments, corresponding to relative momenta between the pair above 400 megaelectronvolts per c (c, speed of light in vacuum). As the relative momentum between two nucleons increases and their separation thereby decreases, we observe a transition from a spin-dependent tensor force to a predominantly spin-independent scalar force. These results demonstrate the usefulness of using such measurements to study the nuclear interaction at short distances and also support the use of point-like nucleon models with two- and three-body effective interactions to describe nuclear systems up to densities several times higher than the central density of the nucleus.

Direct Observation of Proton-Neutron Short-Range Correlation Dominance in Heavy Nuclei.

We measured the triple coincidence A(e,e^{'}np) and A(e,e^{'}pp) reactions on carbon, aluminum, iron, and lead targets at Q^{2}>1.5 (GeV/c)^{2}, x_{B}>1.1 and missing momentum >400 MeV/c. This was the first direct measurement of both proton-proton (pp) and neutron-proton (np) short-range correlated (SRC) pair knockout from heavy asymmetric nuclei. For all measured nuclei, the average proton-proton (pp) to neutron-proton (np) reduced cross-section ratio is about 6%, in agreement with previous indirect measurements. Correcting for single-charge exchange effects decreased the SRC pairs ratio to ∼3%, which is lower than previous results. Comparisons to theoretical generalized contact formalism (GCF) cross-section calculations show good agreement using both phenomenological and chiral nucleon-nucleon potentials, favoring a lower pp to np pair ratio. The ability of the GCF calculation to describe the experimental data using either phenomenological or chiral potentials suggests possible reduction of scale and scheme dependence in cross-section ratios. Our results also support the high-resolution description of high-momentum states being predominantly due to nucleons in SRC pairs.

Plasma aluminium levels in patients on maintenance haemodialysis fall when oral aluminium hydroxide is withdrawn.

In 25 patients on maintenance haemodialysis the mean predialysis plasma aluminium level fell on two occasions when oral aluminium hydroxide was withdrawn for seven and twelve weeks. Substitution of half the prescribed dose of aluminium hydroxide with magnesium hydroxide led to a significant lowering of predialysis plasma aluminium levels over seven months, with no change in plasma phosphate levels. Oral magnesium hydroxide was associated with a mild rise in plasma magnesium levels.

Mercury levels in residents of a geothermal area in the Central North Island.

As a result of previous high trace metal findings in the soil, cattle, vegetation and water of the Broadlands area of New Zealand a study was made of the levels of mercury, selenium, arsenic and zinc in a group of children from this region. Arsenic and zinc levels were found to be normal but significantly raised urinary spot mercury concentrations were found in some of the children when studied in December 1975 and 24 hour urinary mercury concentrations recorded six months later were also raised, but to a lesser degree. Samples of household tap water showed increased mercury concentrations (median 0.001 micromol/L). In agreement with other New Zealand studies the blood selenium concentrations were low (76.7 mu/L) and they did not vary in relation to urinary mercury levels. The children were also examined for signs of peripheral neuropathy but only minor abnormalities were found. The source of the elevated mercury is uncertain but it may come from drinking water or possibly from locally produced meat or vegetables.

The relationship of adenosine triphosphatase activity to tension and power output of insect flight muscle.

1. On a simple model of actomyosin interaction, the tension cost (ATP hydrolysed/unit tension) and the frequency of low amplitude oscillation optimum for work production are both determined by the rate of detachment from the actin filament of the myosin crossbridge. To test this model, the two parameters were measured under different conditions using glycerol-extracted Lethocerus cordofanus dorsal longitudinal flight muscle fibres. 2. The ATPase activity of the static muscle rose by an amount approximately proportional to the rise in tension as the muscle was stretched. 3. When the muscle fibres were sinusoidally oscillated at 5-10 Hz by 2% of their resting length they produced a large amount of mechanical power and hydrolysed approximately twice as much ATP per unit mean tension as they did when static. The ATPase activity was linearly related to the mean tension during oscillation. 4. The experiments were repeated at temperatures between 12 and 30 degrees C and the tension cost and the optimal frequency of oscillation of the fibres were found to rise with temperature. 5. Removal of phosphate from the incubating medium reduced both the tension cost and the optimal working frequency. Addition of pyrophosphate or sulphate reduced both parameters still further. 6. From these results the tension cost of static muscle was shown to be proportional to its optimal working frequency. 7. ATPase activity rose monotonically with power production at work-producing frequencies and at moderate degrees of stretch. A high absolute efficiency was found under a wide range of conditions. 8. The proportionality between tension cost and optimal frequency is evidence for the proposed model of actomyosin interaction.

Effect of Helicobacter pylori infection on colloidal bismuth subcitrate concentration in gastric mucus.

Necropsy gastric mucus infected with Helicobacter pylori has a reduced capacity to concentrate colloidal bismuth subcitrate when compared with non-infected mucus. Mucus mounted in a modified in vitro diffusion chamber was bathed with colloidal bismuth subcitrate solutions at different concentrations and pH levels. Bismuth was measured by atomic absorption spectrophotometry to assess intramucus colloidal bismuth subcitrate concentrations. Bismuth concentrations in non-infected mucus were higher than in Helicobacter pylori infected mucus at all experimental colloidal bismuth subcitrate concentrations and pH levels. Regardless of the infection status, the intramucus concentration of colloidal bismuth subcitrate was dependent upon the concentration of the bathing solution and independent of the pH and the mucus thickness. Colloidal bismuth subcitrate solubility in saline solution varied with pH, and was least soluble in the pH range 1.1 to 3.25 and more soluble above and below this pH range. This study suggests that Helicobacter pylori infection is associated with physicochemical changes in the gastric mucus with a reduction in its capacity to concentrate colloidal bismuth subcitrate. Such a reduction may compromise the attainment of optimum colloidal bismuth subcitrate concentrations necessary for its bactericidal activity.

Hepatic and cerebrospinal fluid accumulation of aluminium and bismuth in volunteers taking short course anti-ulcer therapy.

To investigate the possible absorption and deposition of bismuth or aluminium from agents used in the treatment of peptic ulcers, we have measured levels of bismuth and aluminium in the liver tissue of 15 patients undergoing elective liver biopsy and in the cerebrospinal fluid (CSF) of 15 patients undergoing elective myelography after administration of standard therapeutic doses of tripotassium dicitrato bismuthate (TBS), sucralfate or aluminium hydroxide for 1 month. Aliquots of liver or CSF were separated and levels of both aluminium and bismuth were assayed in each sample by atomic absorption spectrophotometry. The group who received TBS had significantly higher liver bismuth levels than the other two treatment groups, but there was no significant difference in CSF bismuth levels among the three groups. There was no significant difference in either liver or CSF aluminium levels among the three treatment groups. We conclude that tissue accumulation of bismuth may occur after short-course therapy with colloidal bismuth, although there is no evidence of CNS accumulation of bismuth in the present study.

No evidence of a countercurrent multiplier in the intestinal villus of the dog.

The hypothesis that a countercurrent multiplier within the intestinal villus increases osmolality in the distal villus tip was tested. Total sodium, potassium, and water content of intestinal tissue samples was measured. The results showed no significant difference in the total Na plus K concentration (millimoles per kilogram H2O +/- SEM) between the villi tips (185.1 +/- 7.7), whole villi (179.8 +/- 5.4), or intestine minus villi (177.2 +/- 1.7). In contrast, in the kidney (where the existence of a countercurrent multiplier has been demonstrated), the renal medulla had a total Na plus K concentration of 284 +/- 17.1 that was significantly more than the renal cortical concentration of 163 +/- 3.1. Villous tissue osmolality should be in osmotic equilibrium with intestinal luminal fluid. Sampling of intestinal luminal fluid revealed a total Na plus K concentration of 145-165 mmol/kg H2O, a figure compatible with normal luminal osmolality of 280-320 mosmol/kg H2O. These results deny the existence of a countercurrent multiplier in the intestinal villus of the dog.

Adenine nucleotides and ventricular fibrillation.

The isolated perfused rat heart was used to study the influence of adenine nucleotides and their metabolites on vulnerability to ventricular fibrillation. In this model the incidence of ventricular arrhythmias after coronary artery ligation is determined by the extracellular K+ concentration; with perfusate K+ of 2.0 and 3.0 mmol/l hearts develop a high incidence of ventricular arrhythmias and fibrillation while arrhythmias are not encountered with perfusate K+ of 9.0 mmol/l. Assay of adenine nucleotides in uninvolved and ischaemic myocardium of these hearts showed a direct relationship between incidence of ventricular fibrillation and tissue levels of cyclic AMP but not tissue levels of lactate, high energy phosphates, adenosine, inosine and hypoxanthine/xanthine. Administration of dibutyryl cyclic AMP to isolated rat hearts reduced the ventricular fibrillation threshold; this action of cyclic AMP was effectively antagonized by adenosine and its N-ethylcarboxamido analogue but not by 2-chloroadenosine, phenylisopropyladenosine, cyclohexyladenosine and the adenosine deaminase inhibitor, EHNA. 2-Chloroadenosine, like adenosine, inhibited the increase in heart rate caused by DBcAMP. All the adenosine analogues had antiarrhythmic activity against spontaneously occurring ventricular arrhythmias during coronary artery occlusion. Adenosine analogues also antagonized the effect of dibutyryl cyclic AMP whereby it prolongs the QT interval. Adenosine, by as yet incompletely defined mechanisms, may act as an antagonist to the cyclic AMP mediated increase in vulnerability which contributes to the genesis of ventricular fibrillation in the early phase of myocardial ischaemia.

Reduction of bioavailability of aluminium in neonatal parenteral nutrition solutions by prior complexation in the dosage form.

Aluminium (Al ) is abundant in our environment and is a contaminant of electrolyte solutions used in the manufacture of Total Parenteral Nutrition (TPN) solutions administered to neonates, who are unable to tolerate oral feeding. Previous studies by McHalsky et al. (1) have shown concern over the levels of aluminium in parenteral products, and there are special considerations needed with regard to neonatal TPN solutions, (2). It is felt that neurotoxicology and abnormalities of bone histology may be seen with aluminium deposition in the tissues. In the present study it was shown that the average aluminium contamination in TPN solutions was in the order of 205 micrograms/L. It is well documented that aluminium is chelated successfully in dialysis solutions by desferrioxamine (DFO), Allain et al. (3). Using an AA spectrophotometer equipped with a graphite furnace, the average amount of aluminium in compounded neonatal TPN solutions was determined. Equimolar amounts of DFO to aluminium were added to various neonatal TPN formulations, and the physical stability of each solution was determined using microscopic and electronic particle counting analysis. This study suggests that aluminium can be irreversibly chelated with DFO and stable TPN solutions can be prepared.

Simple test of intestinal calcium absorption measured by stable strontium.

A clinical test of intestinal calcium absorption has been developed using non-radioactive stable strontium as a calcium tracer. In nine elderly subjects there was a close correlation between the fractional absorption of strontium and radioactive calcium (45Ca) during a five hour period after the simultaneous oral administration of the two tracers. Comparable precision was achieved with each tracer in six subjects in whom the test was repeated after two weeks. The effect of food on strontium absorption was examined in a further 33 normal subjects (age 21-60 years), and the administration of the strontium with a standard breakfast was shown to reduce the variance at individual time points. A simplified test in which serum strontium concentration was measured four hours after the oral dose given with a standard breakfast was adopted as the routine procedure. The normal range (mean (2 SD], established over 97 tests in 53 patients, was 7.0-18.0% of the dose in the extracellular fluid. A further 30 patients with possible disorders of calcium absorption (10 with primary hyperparathyroidism and 20 with coeliac disease) were studied by this standard test. In both groups of patients the mean four hour strontium values were significantly different from normal. This standard strontium absorption test allows assessment of calcium absorption with sufficient sensitivity and precision to have a wide application in clinical practice.

Tissue distribution of orally administered bismuth in the rat.

1. A colloidal bismuth preparation, tripotassium dicitrato-bismuthate, was given (172 mg/kg body weight, 6/7 days) to 10 laboratory rats for 14 months. Bismuth was measured by atomic absorption spectrometry in various tissues and the pattern of distribution studied. 2. Bismuth was present in kidney lung, spleen, liver, brain, heart and skeletal muscles, in descending order of abundance. Haematological data, renal and liver function tests were normal in the bismuth-treated group. 3. The data suggested that chronic ingestion of bismuth in large doses in rats results in absorption and binding to tissues. Absorbed bismuth probably crosses the blood-brain barrier.

A syndrome of acute zinc deficiency during total parenteral alimentation in man.

Changes in the plasma and urine levels of the trace metal zinc have been followed in a series of 37 adult patients totally supported by intravenous alimentation. Copper has also been determined in more recent cases. In such a seriously ill group, although urinary zinc loss may be very high at the height of catabolism, severe plasma depletion does not occur unless there is a subsequent phase of sustained anabolism and weight gain. In four patients plasma zinc fell to very low levels during this phase and three of this group developed a syndrome characterized by diarrhea, mental depression, para-nasal, oral and peri-oral dermatitis, and alopecia. The response to oral or intravenous zinc therapy is striking, except for hair regrowth which is delayed but eventually complete. The syndrome we have recognized in adult man has not been previously described. It resembles however the parakeratosis of zinc deficient swine and it is also very similar to Acrodermatitis enteropathica, a genetically determined disorder of infants very recently linked to zinc deficiency. Zinc is clearly essential to human metabolism and it should be included in all parenteral alimentation regimes particularly during the period of rapid, sustained, weight gain.

Permissive action of potassium on arrhythmogenesis in the rat heart.

The isolated perfused rat heart was used to assess the influence of extracellular potassium ([K+]0) on vulnerability of the heart to ventricular fibrillation (VF). The VF threshold is reduced when [K+]0 is lowered from 5.9 to 2.0 and 3.0 mmol/l. The vulnerable period is not only widened but VF can be obtained by stimuli on the R wave. The opposite effects are encountered when [K+]0 is increased to 9.0 mmol/l. These alterations in vulnerability to VF are accompanied by an increased incidence of tachyarrhythmias and spontaneous VF during coronary artery ligation and following reperfusion on reduction of [K+]0, with elimination of these arrhythmias on increasing [K+]0 to 9.0 mmol/l. The cellular biochemical responses that accompanied the altered electrical behaviour on alterations of [K+]0 involved the tissue levels of cyclic AMP in both non-ischaemic and ischaemic myocardium and tissue levels of Ca2+ whereas tissue levels of high energy phosphates, adenosine, inosine, hypoxanthine, lactate, Na+, K+ and Mg2+ did not discriminate between hearts vulnerable and hearts resistant to VF. In this model the extracellular K+ level is a determinant of vulnerability to ventricular fibrillation while ischaemic tissue levels of Ca2+ provide the best correlation with alterations in vulnerability.

The assessment of intestinal calcium absorption using stable strontium.

The availability of currently used methods of measuring intestinal calcium absorption is limited by their expense and complexity. Since this measurement may be important in selecting appropriate therapies for patients with osteoporosis, a simpler procedure is required. This paper describes a test which measures the intestinal absorption of stable strontium. A comparison of this test with the single-isotope radio-calcium absorption test in the same group of patients showed a close correlation between the fractional absorption rates of the two elements (r = 0.93, P less than 0.001). Subjects were correctly categorized as having normal or low absorption in 12 out of 13 cases (92%) and the value in the misclassified subject was at the borderline between normal and low calcium absorption. The convenience, low cost, and freedom from radioactivity of stable strontium make it suitable for routine clinical use and, if necessary, repeated testing. If these early results are confirmed, this test will make the assessment of calcium absorption much more widely available.