Variability and trends in the consumption of drugs for treating attention-deficit/hyperactivity disorder in Castile-La Mancha, Spain (1992-2015). / Variabilidad y tendencias en el consumo de fármacos para los trastornos por déficit de atención e hiperactividad en Castilla-La Mancha, España (1992-2015).

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common behavioural disorders of childhood; its prevalence in Spain is estimated at 5-9%. Available treatments for this condition include methylphenidate, atomoxetine, and lisdexamfetamine, whose consumption increases each year. MATERIAL AND METHODS: The prevalence of ADHD was estimated by calculating the defined daily dose per 1,000 population per day of each drug and the total doses (therapeutic group N06BA) between 1992 and 2015 in each of the provinces of Castile-La Mancha (Spain). Trends, joinpoints, and annual percentages of change were analysed using joinpoint regression models. RESULTS: The minimum prevalence of ADHD in the population of Castile-La Mancha aged 5 to 19 was estimated at 13.22 cases per 1,000 population per day; prevalence varied across provinces (p<.05). Overall consumption has increased from 1992 to 2015, with an annual percentages of change of 10.3% and several joinpoints (2000, 2009, and 2012). methylphenidate represents 89.6% of total drug consumption, followed by lisdexamfetamine at 8%. CONCLUSIONS: Analysing drug consumption enables us to estimate the distribution of ADHD patients in Castile-La Mancha. Our data show an increase in the consumption of these drugs as well as differences in drug consumption between provinces, which reflect differences in ADHD management in clinical practice.

Sexual and natural selection in the evolution of extended phenotypes: the use of green nesting material in starlings.

Although sexual selection is typically considered the predominant force driving the evolution of ritualized sexual behaviours, natural selection may also play an important and often underappreciated role. The use of green aromatic plants among nesting birds has been interpreted as a component of extended phenotype that evolved either via natural selection due to potential sanitary functions or via sexual selection as a signal of male attractiveness. Here, we compared both hypotheses using comparative methods in starlings, a group where this behaviour is widespread. We found that the use of green plants was positively related to male-biased size dimorphism and that it was most likely to occur among cavity-nesting species. These results suggest that this behaviour is likely favoured by sexual selection, but also related to its sanitary use in response to higher parasite loads in cavities. We speculate that the use of green plants in starlings may be facilitated by cavity nesting and was subsequently co-opted as a sexual signal by males. Our results represent an example of how an extended phenotypic component of males becomes sexually selected by females. Thus, both natural selection and sexual selection are necessary to fully understand the evolution of ritualized behaviours involved in courtship.

An integrated approach for assessing the bioreceptivity of glazed tiles to phototrophic microorganisms.

A laboratory-based methodology was designed to assess the bioreceptivity of glazed tiles. The experimental set-up consisted of multiple steps: manufacturing of pristine and artificially aged glazed tiles, enrichment of phototrophic microorganisms, inoculation of phototrophs on glazed tiles, incubation under optimal conditions and quantification of biomass. In addition, tile intrinsic properties were assessed to determine which material properties contributed to tile bioreceptivity. Biofilm growth and biomass were appraised by digital image analysis, colorimetry and chlorophyll a analysis. SEM, micro-Raman and micro-particle induced X-ray emission analyses were carried out to investigate the biodeteriorating potential of phototrophic microorganisms on the glazed tiles. This practical and multidisciplinary approach showed that the accelerated colonization conditions allowed different types of tile bioreceptivity to be distinguished and to be related to precise characteristics of the material. Aged tiles showed higher bioreceptivity than pristine tiles due to their higher capillarity and permeability. Moreover, biophysical deterioration caused by chasmoendolithic growth was observed on colonized tile surfaces.

Male Gender and Body Mass Index Are Associated With Hypertension and Reduced Kidney Function 5 or More Years After Living Kidney Donation.

BACKGROUND: The objective of this study was to evaluate renal function and to explore the relationship between some risk factors in kidney donors 12.37 ± 7.60 years after donation. PATIENTS AND METHODS: In a cross-sectional study conducted in a transplant unit, 77 nephrectomized subjects were assessed ≥5 years after donation to evaluate their renal function and the presence or absence of hypertension, dyslipidemia, and microalbuminuria. RESULTS: Twenty donors had an estimated glomerular filtration rate of <60 mL/min/1.73 m(2). Nine donors showed urinary albumin excretion of >20 µg/min (11.68%). Subjects with an EGFR of <60 mL/min were predominantly male and hypertensive and showed higher body mass index (BMI), higher uric acid, higher total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), and logarithm of triglycerides/HDL-C (log TG/HDL-C) ratios than donors with an EGFR of >60 mL/min. Hypertensive donors were older and had higher BMI, higher UA serum values, higher TC/HDL-C and log TG/HDL-C ratios and microalbuminuria than nonhypertensive donors (P < .005). A multivariate analysis was conducted and, after final adjustment, a filtration rate of <60 mL/min was 3.05 times higher in men than women, increased 10% for each 1-unit increase in BMI and was positively associated with log (TG/HDL-C). The frequency of hypertension increased by 10% for each 1-unit increase in BMI and was positively associated with microalbuminuria. CONCLUSION: In this sample of kidney donors from a single transplant unit, ≥5 years after donation, male sex and high BMI were positively associated with the presence of kidney failure.

Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells.

The use of tumor cells as vaccines in cancer immunotherapy is critically dependent on their capacity to initiate and amplify tumor-specific immunity. Optimal responses may require the modification of the tumor cells not only to increase their immunogenicity but also to improve their ability to recruit effector cells to the tumor sites or sites of tumor antigen exposure. It has been reported that CD40 cross-linking of acute lymphoblastic leukemia (ALL) cells significantly increases their immunogenicity and allows the generation and expansion of autologous antileukemia cytotoxic T lymphocytes. This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC. Supernatants from malignant cells cultured in the presence of sCD40L promote the migration of activated T cells that express CCR4, the common specific receptor for MDC and TARC. More importantly, the supernatants from CD40-stimulated tumor cells also support the transendothelial migration of autologous CCR4(+) antileukemia T cells. Therefore, the results demonstrate that the delivery to leukemia cells of a single physiologic signal, that is, CD40 cross-linking, simultaneously improves tumor cell immunogenicity and induces potent chemoattraction for T cells. (Blood. 2001;98:533-540)

Adoptive T-cell therapy for B-cell acute lymphoblastic leukemia: preclinical studies.

We have previously shown that leukemia-specific cytotoxic T cells (CTL) can be generated from the bone marrow of most patients with B-cell precursor acute leukemias. If these antileukemia CTL are to be used for adoptive immunotherapy, they must have the capability to circulate, migrate through endothelium, home to the bone marrow, and, most importantly, lyse the leukemic cells in a leukemia-permissive bone marrow microenvironment. We demonstrate here that such antileukemia T-cell lines are overwhelmingly CD8(+) and exhibit an activated phenotype. Using a transendothelial chemotaxis assay with human endothelial cells, we observed that these T cells can be recruited and transmigrate through vascular and bone marrow endothelium and that these transmigrated cells preserve their capacity to lyse leukemic cells. Additionally, these antileukemia T-cell lines are capable of adhering to autologous stromal cell layers. Finally, autologous antileukemia CTL specifically lyse leukemic cells even in the presence of autologous marrow stroma. Importantly, these antileukemia T-cell lines do not lyse autologous stromal cells. Thus, the capacity to generate anti-leukemia-specific T-cell lines coupled with the present findings that such cells can migrate, adhere, and function in the presence of the marrow microenvironment enable the development of clinical studies of adoptive transfer of antileukemia CTL for the treatment of ALL.

[Renal function aspects in carriers of the human immunodeficiency virus]. / Aspectos da função renal em portadores do vírus da imunodeficiência humana.

The occurrence of alterations was verified in some parameters of the asymptomatic individuals' renal function infected by the virus of the human immunodeficiency (HIV). Forty seven individuals were studied, taking place renal functional tests, as: creatinine clearance, clearance of free water, clearance osmolar, reabsorption tubular proximal and distal of sodium and potassium and urinary pH. The results revealed significant differences (p < 0.05) in the urinary pH, larger in the group with HIV (6.36 +/- 0.41), that in the controls (6.02 +/- 0.41); in the clearance of free water, that indicated reabsorption of larger water in the group with HIV (1.00 +/- 0.64 ml/min) and in the clearance osmolar, that was 2.00 +/- 0.83 ml/min in the group with HIV and 1.57 +/- 0.48 ml/min. The remaining of the indicators of renal function was not shown statistically different between an and other group. It was ended that those differences are significant, in spite of the absolute values they be inside of the normality, because could be associated to late evolutionary alterations of the disease, such as the increase of the frequency of infections of the urinary treatment and the dilution hyponatremia. More studies are necessary for if they confirm those hypotheses.

Aspectos da função renal em portadores do vírus da imunodeficiência humana / Renal function aspects in carriers of the human immunodeficiency virus

Verificou-se a ocorrência de alterações em alguns parâmetros da função renal de indivíduos infectados pelo virus da imunodeficiência humana (HIV), assintomáticos. Foram estudados 47 indivíduos, realizando-se provas funcionais renais: depuração de creatinina endógena, depuração de água livre, depuração osmolar, reabsorção tubular proximal e distal de sódio, excreção fracional de sódio e potássio e pH urinário. Os resultados revelaram diferenças significantes (p < 0,05) no pH urinário, maior no grupo HIV (6,36 ± 0,41), do que nos controles (6,02 ± 0,41); na depuração de água livre, que indicou reabsorção de água maior no grupo HIV (1,00 ± 0,64ml/min), do que nos controles (0,53 ± 0,48ml/min) e na depuração osmolar, que foi 2,00 ± 0,83ml/min no grupo HIV e 1,57 ± 0,48ml/min nos controles. O restante dos indicadores de função renal estudados não se mostraram diferentes estatisticamente entre um e outro grupo. Concluiu-se que essas diferenças são significativas, apesar de os valores absolutos estarem dentro da normalidade, pois podem estar associadas a alterações evolutivas tardias da doença, tais como o aumento na frequência de infecções do trato urinário e a hiponatremia dilucional. Mais estudos são necessários para se confirmarem essas hipóteses.

The occurrence of alterations was verified in some parameters of the asymptomatic individuals' renal function infected by the virus of the human immunodeficiency (HIV). Forty seven individuals were studied, taking place renal functional tests, as: creatinine clearance, clearance of free water, clearance osmolar, reabsorption tubular proximal and distal of sodium and potassium and urinary pH. The results revealed significant differences (p < 0.05) in the urinary pH, larger in the group with HIV (6.36 +/- 0.41), that in the controls (6.02 +/- 0.41); in the clearance of free water, that indicated reabsorption of larger water in the group with HIV (1.00 +/- 0.64 ml/min) and in the clearance osmolar, that was 2.00 +/- 0.83 ml/min in the group with HIV and 1.57 +/- 0.48 ml/min. The remaining of the indicators of renal function was not shown statistically different between an and other group. It was ended that those differences are significant, in spite of the absolute values they be inside of the normality, because could be associated to late evolutionary alterations of the disease, such as the increase of the frequency of infections of the urinary treatment and the dilution hyponatremia. More studies are necessary for if they confirm those hypotheses.

Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40 mg Sb V/kg/dia, de 12/12 h, por 30 dias na forma cutâneo-mucosa de leishmaniose / The evaluation of the tolerance and nephrotoxicity of pentavalent antimony administered in a dose of 40 mg Sb V/kg/day, 12/12 hr, for 30 days in the mucocutaneous form of leishmaniasis

Foi avaliada a função renal de 11 pacientes com leishmaniose cutâneo-mucosa tratados com antimonial pentavalente na dose de 40mg SbV/kg/dia aplicada de 12/12 horas, em esquema contínuo, durante trinta dias. No estudo, um paciente apresentou insuficiência renal reversível e dois desenvolveram alterações enzimáticas hepáticas e eletrocardiográficas sendo o esquema terapêutico interrompido. Nos demais pacientes observou-se efeitos nefrotóxicos tais como diminuição da taxa de filtração glomerular, diminuição da capacidade de concentração urinária, avaliada por um jejum hídrico de 16 horas e aumento na fração de excreção de sódio. No exame do sedimento urinário observou-se um aumento no número de leucócitos e cilindros. Os resultados encontrados neste estudo sugerem que o tratamento com antimonial pentavalente na dose de 40mg SbV/kg/dia foi menos tolerado em virtude de seus efeitos tóxicos, não parecendo apresentar índice de cura superior ao esquema atualmente preconizado de 20mg SbV/kg/dia.

The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40 mg/kg/day of pentavalent antimony (Sb V), in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxic effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40 mg Sb/kg/day was less tolerated on account of its renal toxic effects. This scheme seems not be superior than the currently preconized scheme of 20 mg of Sb V/kg/day during 30 days.

[The evaluation of the tolerance and nephrotoxicity of pentavalent antimony administered in a dose of 40 mg Sb V/kg/day, 12/12 hr, for 30 days in the mucocutaneous form of leishmaniasis]. / Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40 mg Sb V/kg/dia, de 12/12 h, por 30 dias na forma cutâneo-mucosa de leishmaniose.

The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40 mg/kg/day of pentavalent antimony (Sb V), in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxic effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40 mg Sb/kg/day was less tolerated on account of its renal toxic effects. This scheme seems not be superior than the currently preconized scheme of 20 mg of Sb V/kg/day during 30 days.

Effects of water deprivation on renal hydroelectrolytic excretion in chronically Trypanosoma cruzi-infected rats

The effect of an 8 hour-period of water deprivation on fluid and electrolyte renal excretion was investigated in male Wistar rats infected with the strain Sao Felipe (12SF) of Trypanosoma cruzi, in comparison with age and sex matched non-infected controls. The median percent reductions in the urinary flow (-40 per cent v -63 per cent) and excretion of sodium (-57 per cent v - 79 per cent) were smaller in chagasic than in control rats, respectively. So, chagasic rats excereted more than controls. On the other hand, the median percent decrement in the clearance of creatinine was higher in chagasic (-51 per cent) than in controls (-39 per cent). Thus, chagasic rats showed some disturbed renal hydroelectrolytic responses to water deprivation, expressed by smaller conservation, or higher excretion of water and sodium in association with smallerglotmerular filtration rate. This fact denoted an elevation in the fractional excretion of sodium and water.

Effects of water deprivation on renal hydroelectrolytic excretion in chronically Trypanosoma cruzi-infected rats.

The effect of an 8 hour-period of water deprivation on fluid and electrolyte renal excretion was investigated in male Wistar rats infected with the strain São Felipe (12SF) of Trypanosoma cruzi, in comparison with age and sex matched non-infected controls. The median percent reductions in the urinary flow (-40% v-63%) and excretion of sodium (-57% v -79%) were smaller in chagasic than in control rats, respectively. So, chagasic rats excreted more than controls. On the other hand, the median percent decrement in the clearance of creatinine was higher in chagasic (-51%) than in controls (-39%). Thus, chagasic rats showed some disturbed renal hydroelectrolytic responses to water deprivation, expressed by smaller conservation, or higher excretion of water and sodium in association with smaller glomerular filtration rate. This fact denoted an elevation in the fractional excretion of sodium and water.

Insuficiência renal aguda em leishmaniose tegumentar americana tratada com a associaçäo glucantime e alopurinol / Acute renal insufficiency in mucocutaneous leismaniasis reated with glucantime and allopurinol

Os autores apresentam um caso de leishmaniose tegumentar americana causada por Leishmânia viannia brasiliensis que de um grupo de seis pacientes tratados com a associaçäo glucantime e alopurinol desenvolveu quadro de nefrite intersticial aguda acompanhado de exantema cutâneo. Questionam se näo houve potencializaçäo na interaçäo das drogas com relaçäo ao efeito desejável

Pentavalent antimonial nephrotoxicity in the rat

Estudou-se a funcao renal de ratos tratados com Glucantime (Antimoniato de Meglumine, Rhodia) e Pentostam (estibogloconato de Sodio, Wellcome) na dose de 30 mg de "Sb POT v" por 100g de peso por dia, durante 30 dias. Observou-se um disturbio na concentracao urinaria, que foi reversivel 7 dias apos cessada a administracao das drogas. O estudo histopatologico do rim, por meio da microscopia optica, nao evidenciou alteracoes significativas. Por outro lado, ratos tratados com altas doses dos antimoniais (220mg de "Sb POT v" por 100g de peso por dia) mostraram alteracoes funcionais e histopatologicas renais compativeis com necrose tubular aguda

Pentavalent antimonial nephrotoxicity in the rat.

Aspects of the renal function were assessed in rats treated with the pentavalent antimonials Glucantime (Meglumine Antimoniate, Rhodia) or Pentostam (Sodium Stibogluconate, Wellcome). In dose of 30 mg of Sbv (Glucantime or Pentostam) by 100 mg of weight by day for 30 days, renal functional changes were observed consisting of disturbances in urine concentrating capacity. Such disturbances were expressed by significantly low values of urine osmolality as compared to the basal values previous to the drugs. The decrease in urine osmolality was associated to a significant increase in urinary flow and in negative free-water clearance. There was no alteration in osmolar clearance and in fractional excretion of sodium. These observations suggest an interference of the drugs in the action of the antidiuretic hormone. The disturbance in urine concentration was reversible after a seven days period without the drugs administration. No significant histopathological alterations were observed in the kidneys of the rats treated with the drugs. On the other hand, the rats treated with a high dose of Pentostam (200 mg/100 grams of weight/day) showed the functional and the histopathological alterations of the acute tubular necrosis.

High continuous antimony therapy in two patients with unresponsive mucosal leishmaniasis.

The treatment of two patients with severe mucosal leishmaniasis due to Leishmania braziliensis braziliensis is described. Both patients had received much prior antimonial therapy and one had relapsed after a total dose of 2.5 g of Amphotericin B. Both patients responded to prolonged continuous Pentostam therapy at a daily dose of 20 mg Sbv/kg/day for 62 days in one case and for 85 days in the other. Pentavalent antimonials can be curative in such protracted courses in selected patients unresponsive to standard chemotherapy.

Pentavalent antimonial inhibition of the osmotic effect of oxytocin on the isolated toad bladder.

The inhibition of osmotic stimulated water flow in the isolated toad bladder by 0.1 mM sodium stibogluconate (pentavalent antimony) is described. Pentavalent antimony on the serosal surface significantly inhibited oxytocin-induced water flow but when the drug was added to the mucosal surface only the effect of low oxytocin concentrations was reduced. The phosphodiesterase inhibitor pentoxifylline, when present on the serosal side, blocks the effect of pentavalent antimony on stimulated water flow. No effect was detected when indomethacin was present on the serosal side. It is suggested that phosphodiesterase activation might play a role in the mechanism of pentavalent antimonial inhibition of oxytocin-induced water flow in the isolated toad bladder. The effect obtained when sodium stibogluconate on the serosal side was replaced with antimony pentachloride (SbCl5) supports the view that the metal in the molecule is responsible for the inhibition of the effect of oxytocin.