Metformin-associated hyperlactacidaemia acidosis: Diagnosis rate in standard clinical practice and its relationship with renal failure. / Acidosis con hiperlactacidemia por metformina: frecuencia de su diagnóstico en la práctica clínica habitual y relación con la insuficiencia renal.

BACKGROUND AND OBJECTIVES: Observational study on the difference between the number of cases of acidosis with hyperlactacidaemia suspected of being caused by metformin diagnosed in standard clinical practice and the incidence of this condition according to the datasheet. The study also explored the relationship between renal function and metformin-associated hyperlactacidaemia acidosis. PATIENTS: We identified cases of acidosis between 2013 and 2014 by analysing the minimum basic data set and laboratory requests. We selected patients who presented venous lactate levels >2.7 mmol/L at the time they were treated and for whom the use of outpatient metformin was confirmed. The causal relationship with metformin was independently evaluated by several researchers. The incident cases were calculated based on the number of patients who had been dispensed a drug containing metformin during the same period in the study area. RESULTS: We identified 476 cases of acidosis. Metformin was suspected of causing the condition of acidosis with hyperlactacidaemia in 20 of these cases, which represents an incidence rate of 6.57/10,000 patients. Eighty-five percent of the cases presented acute renal failure. CONCLUSIONS: The apparent incidence of acidosis with hyperlactacidaemia in patients treated with metformin is greater than that established in the datasheet (<1/10,000). The onset of metformin-associated hyperlactacidaemia acidosis is related to acute renal impairment.

Enzymatic production of dietary nucleotides from low-soluble purine bases by an efficient, thermostable and alkali-tolerant biocatalyst.

Traditionally, enzymatic synthesis of nucleoside-5'-monophosphates (5'-NMPs) using low water-soluble purine bases has been described as less efficient due to their low solubility in aqueous media. The use of enzymes from extremophiles, such as thermophiles or alkaliphiles, offers the potential to increase solubilisation of these bases by employing high temperatures or alkaline pH. This study describes the cloning, expression and purification of hypoxanthine-guanine-xanthine phosphoribosyltransferase from Thermus thermophilus (TtHGXPRT). Biochemical characterization indicates TtHGXPRT as a homotetramer with excellent activity and stability across a broad range of temperatures (50-90°C) and ionic strengths (0-500mMNaCl), but it also reveals an unusually high activity and stability under alkaline conditions (pH range 8-11). In order to explore the potential of TtHGXPRT as an industrial biocatalyst, enzymatic production of several dietary 5'-NMPs, such as 5'-GMP and 5'-IMP, was carried out at high concentrations of guanine and hypoxanthine.

Influence of the photon orbital angular momentum on electric dipole transitions: negative experimental evidence.

We describe an experiment of atomic spectroscopy devoted to ascertaining whether the orbital angular momentum (OAM) of photons has the same property of interacting with atoms or molecules as occurs for the spin angular momentum (SAM). In our experiment, rubidium vapors are excited by means of laser radiation with different combinations of OAM and SAM, particularly selected to inhibit or enhance the fluorescence according to the selection rules for the electric dipole transitions between the fundamental state and the first excited doublet. Our results clearly show that an electric-dipole-type transition is insensitive to the OAM value, and provide an original validation of a problem long debated in theoretical works.

[Emergent drugs (II): the Pharming phenomenon]. / Drogas emergentes (II): el pharming.

The use of medicines, with or without medical prescription, for recreational ends by the young population has received little attention from doctors. In the USA, one in five adolescents has used medicines for recreational purposes, and consultations in Emergency Departments for medicine abuse have exceeded those for illegal drugs. Although few data are available in Spain, such consumption is situated between 3.1 and 8.6% according to surveys. The medicines most used are dextromethorphan and methylphenidate. The former, on sale without prescription, presents a varied symptomatology, dosage and dependent metabolic action, ranging from euphoria to hallucinations. Methylphenidate, taken orally, nasally or intravenously, is used as a stimulant in substitution for cocaine and is one of the medicines most diverted onto the illicit market at the world level. In principle, other substances like modafinil and propofol present a limited incidence of non-medical use, but they have a probable abuse potential that should be borne in mind, above all in the health context. Finally, opiates like fentanyl, oxycodone and buprenorphine, with new pharmaceutical presentations, have recently become generalized in the therapeutic arsenal of many medical specialities; they are giving rise to phenomena of abuse, dependence and diversion towards the illicit market. Demands for detoxification treatment, their mixture with illegal substances, and cases of death should alert us to the abuse of these medicines.

Drogas emergentes (II): el pharming / Emergent drugs (II): the Pharming phenomenon

El uso por la población joven de fármacos con y sin receta médica con fines recreativos, ha tenido escasa atención por los médicos. En USA, uno de cada cinco adolescentes han usado fármacos con finalidad recreativa, y en el servicio de Urgencias, las consultas por abuso de fármacos han superado a las de drogas ilegales. Aunque es España existen pocos datos, este consumo se sitúa, según las encuestas, entre el 3,1 y el 8,6%.Los fármacos más utilizados son el dextrometorfán y el metilfenidato. El primero, de venta sin receta, presenta una sintomatología variable, dosis y acción metabólica dependiente, el cual varía desde la euforia a las alucinaciones. El metilfenidato se utiliza como estimulante sustituto de la cocaína, tanto por vía oral como nasal e intravenosa, siendo uno de los fármacos con más desvío hacia el mercado ilícito a nivel mundial. Otras sustancias como el modafinilo y el propofol presentan un uso no médico en principio de escasa incidencia, pero con un potencial de abuso a tener en cuenta, sobre todo en el ámbito sanitario. Finalmente, opiáceos como el fentanilo, la oxicodona y la buprenorfina, de reciente generalización en el arsenal terapéutico de muchas especialidades médicas y con nuevas presentaciones farmacéuticas, están produciendo fenómenos de abuso, dependencia y comercio ilícito. Las demandas de tratamiento de desintoxicación, la mezcla con sustancias ilegales y los casos de muerte, alertan sobre el abuso de estos fármacos (AU)

The use of medicines, with or without medical prescription, for recreational ends by the young population has received little attention from doctors. In the USA, one in five adolescents has used medicines for recreational purposes, and consultations in Emergency Departments for medicine abuse have exceeded those for illegal drugs. Although few data are available in Spain, such consumption is situated between 3.1 and 8.6% according to surveys. The medicines most used are dextromethorphan and methylphenidate. The former, on sale without prescription, presents a varied symptomatology, dosage and dependent metabolic action, ranging from euphoria to hallucinations. Methylphenidate, taken orally, nasally or intravenously, is used as a stimulant in substitution for cocaine and is one of the medicines most diverted onto the illicit market at the world level. In principle, other substances like modafinil and propofol present a limited incidence of non-medical use, but they have a probable abuse potential that should be borne in mind, above all in the health context. Finally, opiates like fentanyl, oxycodone and buprenorphine, with new pharmaceutical presentations, have recently become generalized in the therapeutic arsenal of many medical specialities; they are giving rise to phenomena of abuse, dependence and diversion towards the illicit market. Demands for detoxification treatment, their mixture with illegal substances, and cases of death should alert us to the abuse of these medicines (AU)

Suppression of near-Fermi level electronic states at the interface in a LaNiO3/SrTiO3 superlattice.

Standing-wave-excited photoemission is used to study a SrTiO3/LaNiO3 superlattice. Rocking curves of core-level and valence band spectra are used to derive layer-resolved spectral functions, revealing a suppression of electronic states near the Fermi level in the multilayer as compared to bulk LaNiO3. Further analysis shows that the suppression of these states is not homogeneously distributed over the LaNiO3 layers but is more pronounced near the interfaces. Possible origins of this effect and its relationship to a previously observed metal-insulator-transition in ultrathin LaNiO3 films are discussed.

[Sex chromosome abnormality: report of three clinical cases of X pentasomy]. / Anormalità dei cromosomi sessuali: segnalazione di tre casi con pentasomia X.

Pentasomy X cases are very few. In this study we describe three clinical cases (two newborn children and a girl in puberal age) of females showing a 49, XXXXX cariotype. The salient phenotypic characteristics of these cases (heart defects, growth deficiency, craniofacial and hand abnormalities) are compared to the clinico-pathological data described in literature.

Trace gas detection with antimonide-based quantum-well diode lasers.

Widely tunable GaInAsSb/AlGaAsSb quantum well (QW) lasers have been grown by molecular beam epitaxy on GaSb substrates. Their emission wavelength, from 2.0 to 2.5 microm, make them suitable for the detection of many gas species in the wavelength range which corresponds to an atmospheric transmission window. Using these devices an experimental setup for open path gas detection has been developed.

[The clinical syndrome associated with antiphospholipid antibodies. A diagnosis to be confirmed after a long follow-up]. / Sindrome primitiva da anticorpi antifosfolipidi: una diagnosi da confermare nel tempo. Descrizione di un caso clinico.

A clinical case of syndrome of antiphospholipid antibodies is reported. The patient is a 10-year-old girl with thrombophlebitis of the right leg associated with the presence of lupus-like anticoagulant antibodies. No secondary pathologies were found. It is not possible, anyway, to make a definitive differential diagnosis between primary and secondary forms of syndrome of antiphospholipid antibodies because of intermediate situations where antiphospholipid antibodies are associated with 2 or 3 ARA criteria for the diagnosis of lupus (lupus-like syndrome). A long term follow-up is therefore necessary.

[HuEPO treatment of anemia in preterm infants]. / Terapia con HUEPO nell'anemia del pretermine.

The aim of this study is to evaluate how many blood transfusions can be saved by the treatment of anemia in preterm infants (eg < or = 33 weeks) with HUEPO. VLBW infants are at high risk of receiving blood transfusions, following the blood transfusion criteria most applied (45-50% of VLBW infants need blood transfusions). A review of the most recent studies shows that we can save a remarkable number and quantity of blood transfusions in the VLBW infants treated with HUEPO.

Prenatal diagnosis of heterozygosis in a pregnancy at risk for Wolman's disease at the 8th week of gestation.

Wolman's disease is a rare autosomal recessive disease due to lysosomal acid lipase complete deficiency (McKusick 27.800). Prenatal diagnosis is based on safe chorionic villus sampling procedures. We test acid lipase activity in cultured chorionic villus cells, selected from a biopsy performed during the 8th week of pregnancy. We now report the first prenatal diagnosis of heterozygosity for Wolman's disease during the first trimester of pregnancy. Reduced acid lipase activity was shown in the chorionic villi cells using a natural substrate (Cholesterol 14C oleate). The diagnosis was confirmed by the demonstration of reduced acid lipase activity in cultured amniotic cells and in the newborn lymphocytes. Early prenatal diagnosis in pregnancies at risk for lysosomal storage diseases is possible when enzyme activity levels in chorionic villi are similar to those in cultured amniotic cells and in infant cells.

A case of acid lipase deficiency: Wolman's disease.

We report a case of Wolman disease, an unusual autosomal recessive disease characterized by storage of lipid in histiocytes. Storage of cholesteryl esters and triglycerides is caused by lysosomal acid lipase deficiency. This enzyme hydrolyses the cholesteryl esters of LDL thus allowing their peripherical metabolism. Onset of the disease occurs after the first month of life with hepatosplenomegaly, diarrhea, vomiting, abdominal distension, failure to thrive. Diagnosis, suspected because of calcifications of the adrenals was achieved by demonstration of lysosomal acid lipase deficiency in lymphocytes and cultured skin fibroblasts. Carriers of the disease can be identified by enzyme assays in lymphocytes and fibroblasts and prenatal diagnosis can be accomplished by lysosomal acid lipase assays in cultured amniotic fluid cells and chorionic villi.