A. Junod

Diabetogenic action of streptozotocin: relationship of dose to metabolic response

The relationship between the dose of intravenously administered streptozotocin (a N-nitroso derivative of glucosamine) and the diabetogenic response has been explored by use of the following indices of diabetogenic action: serum glucose, urine volume, and glycosuria, ketonuria, serum immunoreactive insulin (IRI), and pancreatic IRI content. Diabetogenic activity could be demonstrated between the doses of 25 and 100 mg/kg, all indices used showing some degree of correlation with the dose administered. Ketonuria was only seen with the largest dose, 100 mg/kg. The most striking and precise correlation was that between the dose and the pancreatic IRI content 24 hr after administration of the drug, and it is suggested that this represents a convenient test system either for both related and unrelated beta cytotoxic compounds or for screening for modifying agents or antidiabetic substances of a novel type. Ability to produce graded depletion of pancreatic IRI storage capacity led to an analysis of the relationship between pancreatic IRI content and deranged carbohydrate metabolism. Abnormal glucose tolerance and insulin response were seen when pancreatic IRI was depleted by about one-third, while fasting hyperglycemia and gross glycosuria occurred when the depletion had reached two-thirds and three-quarters, respectively. The mild yet persistent anomaly produced by the lowest effective streptozotocin dose, 25 mg/kg, exhibits characteristics resembling the state of chemical diabetes in humans and might thus warrant further study as a possible model. Finally, the loss of the diabetogenic action of streptozotocin by pretreatment with nicotinamide was confirmed and was shown to be a function of the relative doses of nicotinamide and streptozotocin and of the interval between injections.

Specific heat in the superconducting and normal state (2–300 K, 0–16 T), and magnetic susceptibility of the 38 K superconductor MgB2: evidence for a multicomponent gap

Abstract The specific heat C of a sintered polycrystalline sample of MgB 2 with a bulk superconducting transition temperature T c =36.7 K is measured as a function of the temperature (2–300 K) and magnetic field (0–16 T), together with magnetic properties (normal-state susceptibility, superconducting-state magnetization, etc.). The Sommerfeld constant γ =0.89±0.05 mJ/K 2 /gat (2.7 mJ/K 2 /mol) is determined in the normal state above H c2 . The normal- and superconducting-state entropies are equal at T c . Several moments of the PDOS are obtained from the lattice specific heat. We report bulk values for: the thermodynamic critical field, B c (0)=0.26 T; the slope of the upper critical field, (d B c2 /d T ) T c =0.56 T/K; the Ginzburg–Landau parameter, κ =38; the coherence length, ξ ≅5 nm; the lower critical field, B c1 ≅0.018 T; the London penetration depth, λ (0)≅180 nm. These results characterize MgB 2 as a type-II superconductor. The nearly quadratic dependence of C ( T ) versus T at T ≪ T c , its non-linear field dependence, and the discrepancy between the electron–phonon coupling constant λ ep as determined by the renormalization of the electron density of states ( λ ep ≅0.6) and by McMillans equation for isotropic superconductors ( λ ep ≅1.1), are inconsistent with a single isotropic gap. In addition to high phonon frequencies, anisotropy or two-band gap structure may explain why the critical temperature of this superconductor is high in spite of its low condensation energy, which does not exceed 1/16 of that of YBa 2 Cu 3 O 7 and 1/4 of that of Nb 3 Sn.

A study of the Cu-O chains in the high Tc superconductor YBa2Cu3O7 by high resolution neutron powder diffraction

Abstract The structure of orthorhombic YBa2Cu3O7 was refined in the temperature interval 5–320K, to an accuracy higher by a factor of about two compared to previous refinements. No major structural change is observed at the onset of superconductivity but the lattice dimensions and some of the structural parameters show small anomalies near 90K and 240K. All vibrational amplitudes are normal except for those of the 04 atoms across the Cu-O chain, which are large. Good agreement with the data is obtained by assuming that the 04 atoms are located on potential minima away by at least 0.08A from the chain axis at all temperatures. Annealing near 240K to look for a possible order-disorder transition revealed no structural changes.

Phenomenological two-gap model for the specific heat of MgB2

The authors show that the specific heat of the superconductor MgB{sub 2} in zero field, for which significant non-BCS features have been reported, can be fitted, essentially within experimental error, over the entire range of temperature to T{sub c} by a phenomenological two-gap model. The resulting gap parameters agree with previous determinations from band-structure calculations, and from various spectroscopic experiments. The determination from specific heat, a bulk property, shows that the presence of two superconducting gaps in MgB{sub 2} is a volume effect.

Variation of the superconducting properties of Bi2Sr2CaCu2O8+x with oxygen content

Abstract We have mapped the critical temperature of Bi 2 Sr 2 CaCU 2 O 8+δ (2212) in the ( p, T ) plane for 10 −5 ≤ p ≤ 80 bar (O 2 ) and 300 ≤ T ≤ 840°C. Equilibrium conditions are frozen by quenching the samples into liquid gallium. The DC diamagnetic transitions remain sharp, and span an unusual temperature range for the 2212 phase (51.5 K to 94.4 K). This variation is attributed to a measured 2.5% change of the oxygen content ( Δδ ⋍ 0.2 ) in the structure. At the same time, we do not observe any significant variation of the lattice parameters. The Meissner effect, measured in an external magnetic field of 20 Oe, increases with T c . The slope of the normal-state susceptibility ∂ χ / ∂T becomes markedly less negative with decreasing oxygen concentration. It vanishes for the optimum doping that leads to T c ⋍ 94 K .

Specific heat of single crystal MgB2: a two-band superconductor with two different anisotropies.

Heat-capacity measurements of a 39 microg MgB2 single crystal in fields up to 14 T and below 3 K allow the determination of the low-temperature linear term of the specific heat, its field dependence, and its anisotropy. Our results are compatible with two-band superconductivity, the band carrying the smaller gap being isotropic, that carrying the larger gap having an anisotropy of approximately 5. Three different upper critical fields are thus needed to describe the superconducting state of MgB2.

Optimization of the specific heat jump at Tc and magnetic properties of the superconductor YBa2Cu3O7

Abstract A number of high-quality polycrystalline YBa 2 Cu 3 O 7 samples were investigated by specific-heat measurements from 30 to 300 K, with emphasis on the second-order transition at T c . The same samples were examined for their Meissner effect, the normal state magnetic susceptibility and crystal structure parameters. A clear correlation was established between the normal state susceptibility and the specific-heat discontinuity Δ C at T c , a fact allowing us to separate the exchange enhanced Pauli contribution. The results impose a constraint on the ratio of the Stoner factor S and the mass renormalization 1 + λ through S /(1 + λ ) = 0.42 A ( λ ), where A ( λ ) = ΔC / γT c . The transition temperature is insensitive even to pronounced variations of the density of states.

Preventing stroke recurrence in patients with patent foramen ovale: Antithrombotic therapy, foramen closure, or therapeutic abstention? A decision analytic perspective

Emphasis on the role of patent foramen ovale as a potential risk factor for ischemic paradoxical stroke has recently increased. Current therapeutic options for secondary stroke prevention include long-term antithrombotic therapies and invasive closure of the defect, but selective indications have not been evaluated. Therefore we developed a Markov-based decision analysis model for a hypothetical cohort of patients 55 years of age with presumed paradoxical embolism, measuring for each therapy the risks of stroke recurrence, treatment-related complications, and death after 5 years and the quality-adjusted life-years. Over a wide range of stroke risk recurrence (0.8% per year to 7% per year), the gain provided by closure of the defect exceeded the one obtained by other therapeutic options. When the risk exceeded 0.8% per year and 1.4% per year, respectively, this was also verified for anticoagulation and antiplatelet therapies compared with therapeutic abstention. Therapeutic abstention was the preferred strategy under 0.8% per year. Sensitivity analyses identified key parameters influencing the choice of therapy. These included estimates of stroke recurrence, bleeding rates, surgery-related case fatality rates, and age. Considering the risks of treatment and the devastating consequences of a recurrent stroke, our model suggests that if the estimated risk of paradoxical stroke recurrence is > 0.8% per year, therapeutic abstention becomes the worst option. Above this threshold secondary stroke prevention with anticoagulation therapy or surgical closure of the defect is the preferred strategy, and assessment of both the risk of stroke recurrence and the risk related to therapeutic options should guide individual therapeutic decision making.

Organ culture of fetal rat pancreas II. Insulin release induced by amino and organic acids, by hormonal peptides, by cationic alterations of the medium and by other agents

1. 1. The effect of noncarbohydrate agents and of alterations in the cationic environment on insulin release has been studied in cultured fetal pancreatic explants of the rat. 2. 2. Tolbutamide alone (81 μg/ml) induced some insulin release. It was clearly more effective, however, in the presence of 11 mM glucose and even more so in the presence of 10 mM caffeine. The smallest effective tolbutamide concentration in the presence of glucose was 9 μg/ml. 3. 3. Glucagon (3.2 μg/ml) elicited a modest insulin release, which was enhanced by addition of 10 mM caffeine and more markedly by 11 mM glucose. The smalelst effective dose in the presence of glucose was 50 ng/ml. A preparation of “gut extract” stimulated the release of insulin in the presence of glucose, while corticotropin and secretin were ineffective. 4. 4. Organic acids were tested at the concentration of 11 mM in the presence of caffeine. Citrate and octanoate enhanced insuling release, whereas glutamate, succinate and fumarate were inhibitory. Neither acetate nor β-hydroxybutyrate altered insulin output. 5. 5. All of the amino acids studied (concentration of 11 mM) stimulated the output of insulin in the presence of caffeine. Lysine was most effective, followed by threonine, arginine and leucine. The least active amino acids were histidine and phenylalanine. 6. 6. The omission or the presence of an excess of K+ in the incubation medium stimulated insulin output and, furthermore, enhanced the stimulatory effect of glucose and/or caffeine. Ouabain enhanced the glucose- and caffeine-induced insulin release but only at the relatively high concentration of 1 mM. Lowering of the Na+ concentration in the medium suppressed the stimulatory effect of the ommission of K+ but was without inhibitory effect at higher K+ concentrations. 7. 7. Omitting Ca2+ from the medium diminished the insulin release induced by glucose and caffeine, either in the absence of K+ or in its presence at normal or high concentrations, whereas omitting Mg2+ had no inhibitory effect. 8. 8. These results were interpreted as consistent with the hypothesis that insulin release from our preparation is dependent, at least in part, upon activation of the adnyl cyclase syste.

Variation of the superconducting and structural properties of Y2Ba4Cu7Oz with oxygen content (14.1 < z < 15.3, 30 K ⩽ Tc ⩾ 95 K)

A great number of pure and homogeneous Y2Ba4Cu7Oz samples were investigated by AC susceptibility, field cooling magnetization measurements, X-ray diffraction, microprobe analysis and microstructural examinations in a light microscope and a scanning electron microscope. The oxygen content z between 14.1 and 15.3 was determined by the reduction of the samples in a hydrogen flow. To reach the (z-T-p) equilibrium, well-crystallized samples were annealed in pure oxygen (10−6 ⩽p(O2)⩽102 bar) between 300 and 900°C and subsequently quenched. The specimens produced in this way show sharp χAC transitions in the entire range of critical temperatures (30 K ⩽ Tc ⩽ 95 K). The correlation Tc versus the orthorhombicity 2(b−a)/(b+a) is almost linear, similar to that observed in YBa2Cu3Ox. This is contrast to the distinct behaviour of the functions Tc versus z and Tc versus x in these two compounds. We present a stability-decomposition map 0for Y2Ba4Cu7Oz over a wide range of (T, p) coordinates.