[Prevalence of hypophosphatasia in adult patients in rheumatology]. / Prävalenz der Hypophosphatasie bei adulten Patienten in der Rheumatologie.

BACKGROUND: Hypophosphatasia (HPP) is a genetic disorder caused by one or more mutations in the alkaline phosphatase (ALP) gene, responsible for encoding tissue-specific ALP and for the mineralization process. OBJECTIVE: Identification of the prevalence of HPP in rheumatology patients. MATERIAL AND METHODS: Medical records of all adult rheumatology patients with pathologically low total ALP levels (<35 U/L) treated in the Department of Rheumatology at the Clinic of Internal Medicine III, University Hospital Bonn between January 2017 and June 2019, were retrospectively examined for clinical signs as well as for results of genetic tests for HPP. RESULTS: In 60 out of 2289 patients (2.62%) pathologically low ALP levels were detected. Of these 30 (1.31%) were found to have persistently low ALP levels. Genetic testing for ALP gene mutations was performed in 19 of these 30 patients and 7 of the 19 patients (36.84%) had HPP signs (insufficiency fractures, or bad dental status since childhood), all with pathologic ALP mutations. Of these patients 3 (15.78%) each had a history of insufficiency fracture with normal bone densitometry. Overall, 13 out of the 19 patients (68.42%) had mutations in the ALP gene. Interestingly, no association with chondrocalcinosis was detected in any of the patients. CONCLUSION: The HPP seems to be an underdiagnosed disease with a higher proportion of affected rheumatology patients. Therefore, future studies should aim to develop a diagnostic protocol in the clinical practice.

g Factor of the

The gyromagnetic factor of the low-lying E=251.96(9) keV isomeric state of the nucleus ^{99}Zr was measured using the time-dependent perturbed angular distribution technique. This level is assigned a spin and parity of J^{π}=7/2^{+}, with a half-life of T_{1/2}=336(5) ns. The isomer was produced and spin aligned via the abrasion-fission of a ^{238}U primary beam at RIKEN RIBF. A magnetic moment |µ|=2.31(14)µ_{N} was deduced showing that this isomer is not single particle in nature. A comparison of the experimental values with interacting boson-fermion model IBFM-1 results shows that this state is strongly mixed with a main νd_{5/2} composition. Furthermore, it was found that monopole single-particle evolution changes significantly with the appearance of collective modes, likely due to type-II shell evolution.

Shape coexistence in the neutron-deficient even-even (182-188)Hg isotopes studied via coulomb excitation.

Coulomb-excitation experiments to study electromagnetic properties of radioactive even-even Hg isotopes were performed with 2.85 MeV/nucleon mercury beams from REX-ISOLDE. Magnitudes and relative signs of the reduced E2 matrix elements that couple the ground state and low-lying excited states in Hg182-188 were extracted. Information on the deformation of the ground and the first excited 0+ states was deduced using the quadrupole sum rules approach. Results show that the ground state is slightly deformed and of oblate nature, while a larger deformation for the excited 0+ state was noted in Hg182,184. The results are compared to beyond mean field and interacting-boson based models and interpreted within a two-state mixing model. Partial agreement with the model calculations was obtained. The presence of two different structures in the light even-mass mercury isotopes that coexist at low excitation energy is firmly established.

Determination of prostaglandin profiles in lipopolysaccharide-challenged guinea pig spleen.

We previously reported that splenic extract from lipopolysaccharide (LPS)-challenged guinea pigs inhibits the exaggerated febrile response of splenectomized guinea pigs, suggesting that the spleen generates an inhibitory factor. Earlier results indicate that the factor is a lipid. In an effort to identify this factor, lipid fractions, isolated from splenic extracts of control and LPS-challenged guinea pigs, were analyzed with emphasis on identifying and quantifying prostanoids, which according to current knowledge are the likely bioactive factors. Prostaglandins have been extensively implicated in central and peripheral thermoregulation, and thus these lipids were targeted for characterization in the spleen. Analysis was done on the splenic extracts using solid-phase extraction, analytical and preparative thin-layer chromatography (TLC) and high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Four prostaglandins (PGs, 6-keto-PGF(1α) , PGF(2α) , PGE(2) and PGD(2) ) were identified and quantified. Our data shows that these PG levels are doubled in LPS-treated guinea pig spleen compared with the control group. The methods used in this investigation to characterize PG in the spleen offer significant advantages over immunoassays previously used to identify and quantify PG in the spleen and other biological tissues. These methods will be utilized in further research needed to definitively characterize the role of splenic-derived PG in modulation of the febrile response induced by LPS.

Is the 7/2(1)- isomer state of 43S spherical?

We report on the spectroscopic quadrupole moment measurement of the 7/2(1)(-) isomeric state in (16)(43)S(27) [E*=320.5(5) keV, T(1/2)=415(3) ns], using the time dependent perturbed angular distribution technique at the RIKEN RIBF facility. Our value, |Q(s)|=23(3) efm(2), is larger than that expected for a single-particle state. Shell model calculations using the modern SDPF-U interaction for this mass region reproduce remarkably well the measured |Q(s)|, and show that non-negligible correlations drive the isomeric state away from a purely spherical shape.

Rat lung Cu,Zn superoxide dismutase. Isolation and sequence of a full-length cDNA and studies of enzyme induction.

The synthesis of Cu,Zn SOD by rat lung increases spontaneously in the fetus in late gestation and during exposure of neonatal and adult rats to greater than 95% O2. To explore the regulation of these increases, we measured rat lung Cu,Zn SOD synthesis and activity. We also cloned and sequenced a rat lung Cu,Zn SOD cDNA that was used to measure Cu,Zn SOD mRNA concentration. We found that (a) under normal gestational and postgestational conditions the synthesis of this enzyme was regulated pretranslationally; (b) the increased synthesis that occurs under hyperoxia (greater than 95% O2), was pretranslationally mediated in otherwise unmanipulated neonatal rats but translationally controlled in hyperoxic adult rats; and (c) in lungs of rats made tolerant to greater than 95% O2 by allowing 24 h rest in air after an initial 48 h in greater than 95% O2, the increased Cu,Zn SOD synthesis that occurred during the second period of hyperoxia was regulated pretranslationally. We conclude Cu,Zn SOD gene expression in the lung is developmentally regulated under normal conditions and in response to an oxidant challenge. Tolerance, whether endogenous or induced, appears to require the accumulation of increased amounts of Cu,Zn SOD mRNA.

Surfactant cholesterol metabolism of the isolated perfused rat lung.

1. The isolated perfused rat lung was used as the principal model to study surfactant cholesterol metabolism. 2. Cholesterol was found to represent over 50% of the neutral lipid of both the total surfactant and the lamellar body fractions. 3. De novo synthesis of cholesterol from [1-14C]acetate accounted for only 1% of the surfactant cholesterol, the remainder being derived from exogenous cholesterol supplied as serum lipoproteins. 4. Lipoprotein [1,2-3H2]cholesterol was incorporated into the lamellar body and extracellular surfactant fractions. The increase in the cholesterol specific activities of these fractions with time was consistent with a precursor-product relationship between the lamellar body cholesterol and that of the extracellular surfactant. 5. Incorporation of [methyl-14C]choline and [1,2-3H2]cholesterol indicated that the metabolism and secretion of lamellar body and extracellular surfactant cholesterol parallels that of phosphatidylcholine and suggests that most if not all extracellular surfactant cholesterol is derived from the lamellar body. 6. Comparison of the relative specific activities of incorporated [1,2-3H2]-cholesterol indicate that 59% of the total surfactant cholesterol is located extracellularly.

Mitogenic response of rat lung to endotoxin exposure.

Adult rats exposed to hyperoxia are protected from lung injury by treatment with bacterial endotoxin. Experiments were undertaken to determine whether endotoxin treatment produces a mitogenic effect on the lung. Endotoxin treatment caused a significant (P less than .05) loss of body weight (8%) in rats exposed to either air or greater than 95% O2 for 24 hr. Therefore, experiments were also undertaken in which both saline- and endotoxin-treated rats were starved for the duration of the experiments to make equal any nutritional imbalance. The rate of DNA synthesis in lung slices from fed rats treated with endotoxin did not differ from that of saline-treated controls. In contrast, lung DNA synthesis in starved rats treated with endotoxin increased 50%. The effect of endotoxin treatment was similar in rats breathing air or greater than 95% O2, and lung protein synthesis generally paralleled lung DNA synthesis. These results indicate that endotoxin does exert a mitogenic effect on the lung and this effect can be masked by the nutritional imbalance resulting from endotoxin administration.

The effect of partial outlet obstruction on prostaglandin generation in the rabbit urinary bladder.

Partial outlet obstruction of the urinary bladder has been demonstrated to induce specific dysfunctions in cellular and sub-cellular membrane structures within the bladder's smooth muscle and mucosal compartments. Recent studies have linked these membrane dysfunctions to alterations in phospholipid metabolism leading to mobilization of free arachidonic acid, the precursor for synthesis of prostaglandins (PG). The purpose of this study was to determine if partial outlet obstruction of the urinary bladder induces changes in the capacity of bladder smooth muscle and mucosa to generate PG. PG were isolated from control and partially obstructed urinary bladder smooth muscle and mucosa of male New Zealand White (NZW) rabbits. PG concentrations (PGE2, PGF2alpha and PGI2, as its stable metabolite 6-keto-PGF1alpha) were determined after 30 minute incubations using enzyme-linked immunoassay (ELISA) kits. In both control and obstructed rabbit urinary bladders, PG generation was significantly higher in isolated mucosa than muscle tissues. A significantly higher concentration of PGF2alpha, and 6-keto-PGF1alpha was measured in obstructed muscle tissue relative to controls. The concentration of 6-keto-PGF1alpha was also significantly higher than the concentrations measured for PGE2 and PGF2alpha in both control and obstructed smooth muscle samples. The generation of PGE2 was significantly higher in rabbit urinary bladder mucosa than either PGF2alpha or 6-keto-PGF1alpha in both control and obstructed samples. The capacity of obstructed mucosal tissue to generate 6-keto-PGF1alpha was significantly higher than control tissue, while no significant differences in PGE or PGF2alpha generation were noted. These data suggest obstruction of the urinary bladder induce specific elevations in PG in both smooth muscle and mucosal tissues.

Regulation of lung surfactant cholesterol metabolism by serum lipopoteins.

The isolated perfused rat lung was used as an experimental model in the study of the lipoprotein regulation of surfactant cholesterol metabolism. Addition of low density lipoproteins (LDL) to the perfusion medium at a cholesterol concentration of 0.5 micrometer had no inhibitory effect on [1-14C]-acetate incorporation into cholesterol of either the surfactant or residual fractions. Increasing the concentration of cholesterol in the medium to 2.5 micrometer resulted in significant inhibition of incorporation into cholesterol of both fractions. A similar inhibition resulted when lungs were perfused with 2.5 micrometer cholesterol in the form of high density lipoproteins (HDL). No inhibition of fatty acid synthesis, measured as incorporation into cholesteryl esters, was observed. The rate of uptake by perfused lung of cholesterol from both high and low density lipoproteins was similar. Competitive binding studies with 125I-labeled lipoproteins indicated the existence of lung receptors for both classes of lipoprotein. The rate of uptake of the apoprotein moiety of low density lipoproteins was significantly greater than that of high density lipoproteins. These data suggest that lung cholesterol metabolism may be subject to regulation by both low and high density serum lipoproteins.

Efficacy of morphine sulfate-augmented hepatobiliary imaging in acute cholecystitis.

OBJECTIVE: A review of the English language literature was performed to determine the sensitivity and specificity of morphine sulfate-augmented hepatobiliary imaging for acute cholecystitis. Twenty publications, involving 914 patients, were reviewed from journals published between 1984 and 1999. The analysis of these patients has resulted in the largest combined review study to date. The sensitivity and specificity of morphine-augmented hepatobiliary imaging were calculated to be 96.1% and 88.6%, respectively. After reading this paper, the nuclear medicine technologist should be able to: (a) discuss the clinical use of morphine augmentation during hepatobiliary imaging; and (b) state the sensitivity and specificity of morphine sulfate-augmented hepatobiliary imaging.

Calcaneal osteotomy for retrocalcaneal exostosis.

In cases in which radiographic and clinical criteria warrant surgical management of Haglund's deformity, calcaneal osteotomy should be considered. Although postoperative recuperation is extended with this procedure as compared with simple exostectomy, the long-term results have proved more successful. Because of the relative technical difficulty in performing the procedure, perioperative planning and anatomic considerations are essential.

Efficacy, safety and regulatory status of SGLT2 inhibitors: focus on canagliflozin.

Prevalence of diabetes mellitus is inc6reasing, with a burden of 382 million patients worldwide at present (more than the entire US population). The International Diabetes Federation anticipates an increase up to 592 million patients by 2035. Another major problem arises from the fact that just 50% of patients with type 2 diabetes mellitus are at target glycaemic control with currently available medications. Therefore, a clear need for new therapies that aim to optimize glycaemic control becomes evident. Renal sodium-linked glucose transporter 2 inhibitors are new antidiabetic drugs with an insulin-independent mechanism of action. They pose one remarkable advantage compared with already established antidiabetics: increasing urinary glucose excretion without inducing hypoglycaemia, thereby promoting body weight reduction due to loss of ~300 kcal per day. This review focuses on canagliflozin, which was the first successful compound of this class to be approved by both the US Food and Drug Administration and the European Medicines Agency in 2013. Clinical trials showed promising results: enhancing glycaemic control was paralleled by reducing body weight and systolic and diastolic blood pressure. Nevertheless, some safety concerns remain, such as genital mycotic infections, urinary tract infections and cardiovascular risks in vulnerable patients, which will be closely monitored in several post-authorization safety studies.