Simultaneous quantification of ticagrelor and its active metabolite, AR-C124910XX, in human plasma by liquid chromatography-tandem mass spectrometry: Applications in steady-state pharmacokinetics in patients

A sensitive and simple liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of ticagrelor and its active metabolite, AR-C124910XX from 50 µL human plasma using tolbutamide as an internal standard as per regulatory guidelines. Analytes in plasma were extracted by simple protein precipitation using acetonitrile, followed by chromatographic separation with an Acclaim™ RSLC 120 C₁₈ column (2.2 µm, 2.1 × 100 mm) and a gradient acetonitrile-water mobile phase containing 0.1% formic acid within 8 min. Mass spectrometric detection and quantitation were conducted by selected reaction-monitoring on a negative electrospray ionization mode with the following transitions: m/z 521.11 → 361.10, 477.03 → 361.10, and 269.00 → 169.60 for ticagrelor, AR-C124910XX, and tolbutamide, respectively. The lower limit of quantifications was 0.2 ng/mL with linear ranges of 0.2–2,500 ng/mL (r² ≥ 0.9949) for both analytes. All validation data, including selectivity, cross-talk, precision, accuracy, matrix effect, recovery, dilution integrity, stability, and incurred sample reanalysis, were well within acceptable limits. This assay method was validated using K₂-EDTA as the specific anticoagulant. Also, the anticoagulant effect was tested by lithium heparin, sodium heparin, and K₃-EDTA. No relevant anticoagulant effect was observed. This validated method was effectively used in the determination of ticagrelor and its active metabolite, AR-C124910XX, in plasma samples from patients with myocardial infarction.

A Portulaca oleracea L. extract promotes insulin secretion via a K⁺(ATP) channel dependent pathway in INS-1 pancreatic β-cells

BACKGROUND/OBJECTIVE: This study was designed to investigate how a Portulaca oleracea L. extract (POE) stimulates insulin secretion in INS-1 pancreatic β-cells. MATERIALS/METHOD: INS-1 pancreatic β-cells were incubated in the presence of various glucose concentrations: 1.1 or 5.6, 16.7 mM glucose. The cells were treated with insulin secretagogues or insulin secretion inhibitor for insulin secretion assay using an insulin ELISA kit. In order to quantify intracellular influx of Ca2+ caused by POE treatment, the effect of POE on intracellular Ca2+ in INS-1 pancreatic β-cells was examined using Fluo-2 AM dye. RESULTS: POE at 10 to 200 µg/mL significantly increased insulin secretion dose-dependently as compared to the control. Experiments at three glucose concentrations (1.1, 5.6, and 16.7 mM) confirmed that POE significantly stimulated insulin secretion on its own as well as in a glucose-dependent manner. POE also exerted synergistic effects on insulin secretion with secretagogues, such as L-alanine, 3-isobutyl-1-methylxanthine, and especially tolbutamide, and at a depolarizing concentration of KCl. The insulin secretion caused by POE was significantly attenuated by treatment with diazoxide, an opener of the K+ ATP channel (blocking insulin secretion) and by verapamil (a Ca2+ channel blocker). The insulinotropic effect of POE was not observed under Ca2+-free conditions in INS-1 pancreatic β-cells. When the cells were preincubated with a Ca2+ fluorescent dye, Fluo-2 (acetoxymethyl ester), the cells treated with POE showed changes in fluorescence in red, green, and blue tones, indicating a significant increase in intracellular Ca2+, which closely correlated with increases in the levels of insulin secretion. CONCLUSIONS: These findings indicate that POE stimulates insulin secretion via a K+ ATP channel-dependent pathway in INS-1 pancreatic β-cells.

Study of change in activity of hepatic drug metabolism enzymes in rat model of chronic unpredictable mild stress / 药学学报

This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.

Antihyperglycemic and hypolipidemic effects of Hibiscus schizopetalus [Mast] Hook in alloxan-induced diabetic rats

The antihyperglycemic and hypolipidemic activities of Hibiscus schizopetalus [Mast] Hook [Malvaceae] flower and leaves extracts were investigated in alloxan-induced diabetic rats. The hypoglycemic activity of both the extracts [100mg/kg, body weight] was tested in fasting normal rat, glucose loaded rats. Observation on body weight was also recorded. The extracts showed a significant [P<0.001] reduction in blood glucose level in normal fasting rats. In glucose tolerance test, significant [P<0.01] decreased observed in all glucose loaded animals. While in alloxan induced diabetic rats, the percent blood glucose reduction was 59.94% and 45.14% in extracts treated groups. The results obtained were compared with the reference standard drug Tolbutamide [100mg/kg, body weight]. The diabetic rats showed sign of decreased in their body weight during the treatment period. Cholesterol and triglycerides levels were significantly decreased [P<0.001] by HFE. The results obtained demonstrated the potential hypoglycemic activity of methanolic extracts of H. schizopetalus. There is need of bioassay-directed assay of the active principles responsible for the anti-diabetic activity. The methanolic extracts showed the presence of carbohydrates, alkaloids, steroids, terpenes, saponins and glycosides.

CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs.</p><p><b>METHOD</b>Cocktail probe drugs method has been established, an LC-MS/MS analytical method has been established to determine the five probes of midazolam, phenacetin, dextromethorphan, tolbutamide, chlorzoxazone and the internal standard was benzhydramine to evaluate the effect of CYP450 activity following administration of berberine in pooled human liver microsomes.</p><p><b>RESULT</b>Compared with control group, the pharmacokinetics of midazolam, phenacetin and tolbutamide were no significant differences, but the pharmacokinetics of chlorzoxazone was significantly decreased. There were no significant differences for the pharmacokinetics of dextromethorphan when the concentration of berberine was 50 microg x L(-1). The pharmacokinetics of dextromethorphan was significantly decreased when the concentration of berberine was exceed 200 microg x L(-1).</p><p><b>CONCLUSION</b>Berberine has no influence on the activities of CYP3A4, CYP1A2 and CYP2C19 below 2 000 microg x L(-1), but can inhibit the activity of CYP2E1 and CYP2D6 in concentration-dependent.</p>

Assessment of CYP2B6 activity in rats: a cocktail study with bupropion alone and in combined with tolbutamide

A "cocktail"of numerous probe drugs to assess the metabolic activity of the corresponding cytochrome P450 enzymes requires that there is no problem of interaction among them. Some interactions among probe drugs can appear and may affect the rate of biotransformation of other ones. To develop a useful "cocktail" of probe drugs, our presented work was aimed on the influence of tolbutamide on cytochrome P450-mediated metabolism of bupropion. The biotransformation rates of bupropion administered either separately or in combined with tolbutamide were compared in this new study. The results revealed that tolbutamide had significantly decreased the rate of bupropion hydroxylation. Thus, due to shift in cytochrome P450 enzyme metabolic activity some extent differential results in the rate of P450-mediated metabolism can be observed when comparing assessment using combination of two model drugs with the common way [single marker use]

Effects of brucine combined with glycyrrhetinic acid or liquiritin on rat hepatic cytochrome P450 activities in vivo / 药学学报

Abstract: The activities of four CYP450 enzymes (CYP3A, 1A2, 2El and 2C) and the mRNA expression levels of CYP1A2, 2El, 2Cll and 3A1 in rat liver were determined after Wistar rats were orally administered with brucine (BR) at three dosage levels (3, 15 and 60 mg.kg-1 per day) and the high dose of BR combined with glycyrrhetinic acid (GA, 25 mg.kg-1 per day) or liquiritin (LQ, 20 mg.kg-1 per day) for 7 consecutive days. Compared with the control, brucine caused 24.5% and 34.6% decrease of CYP3A-associated testosterone 6beta-hydroxylation (6betaTesto-OH) and CYP2C-associated tolbutamide hydroxylation (Tol-OH), respectively, and 146.1% increase of CYP2El-associated para-nitrophenol hydroxylation (PNP-OH) at the high dose level. On the other hand, (BR+GA) caused 51.4% and 33.5% decrease, respectively, of CYP2El-associated PNP-OH and CYP1A2-associated ethoxyresorufin-O-de-ethylation (EROD) as compared with the high dose of BR group. Meanwhile, (BR+LQ) caused 41.1% decrease of CYP2El-associated PNP-OH and 37.7% increase of CYP2C-associated Tol-OH. The results indicated that the co-administration of BR with GA or LQ had effect on mRNA expression and activities of the CYP450 enzymes mentioned above to some extent, and the in vivo antagonism of LQ on BR-induced CYPs adverse effects and the in vivo inhibitory action of GA on CYP2E1 and 1A2 might play an important role in the detoxification of Radix Glycyrrhizae against Strychnos nux-vomica L.

Hypolipidaemic & hepatoprotective effects of Psidium guajava raw fruit peel in experimental diabetes.

Background & objective: The study evaluated the hypolipidaemic and hepatoprotective effects of unripe Psidium guajava fruit peel aqueous extract in streptozotocin (STZ) induced severely diabetic rats by assaying their triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, alkaline phosphatase (ALKP), asperate amino transeferase (AST), alanine amino transferase (ALT) and creatanine (CRTN) levels. Method: Severely diabetic albino Wister rats of same age group were treated orally once a day upto 3wk with a dose of 400 mg/kg bw of lyophilized extract. TG, TC, HDL, ALKP, AST, ALT and CRTN were estimated. LDL and VLDL cholesterol levels were calculated from the above measurements by using Friedwald formula. Results: A significant decrease in TG (P<0.01), TC (P<0.01), HDL (P<0.001) VLDL (P<0.001) and LDL (P<0.01), ALKP (P<0.01), AST (P<0.05), ALT (P<0.05) and CRTN (P<0.001) levels were observed after 21 days treatment of aquous extract of raw fruit peel compared to pre treatment levels. Interpretation & conclusion: The extract showed significant hypolipidaemic activity in addition to its hypoglycaemic and antidiabetic activity. In view of its relative non-toxic nature P. guajava raw fruit peel may be a potential antidiabetic agent.

Diabetes melito neonatal: [revisão] / Neonatal diabetes mellitus: [review]

O diabetes neonatal (DN) é uma condição rara caracterizada por hiperglicemia, que necessita de tratamento com insulina, diagnosticado nos primeiros meses de vida. Clinicamente pode ser classificado em DN transitório quando ocorre remissão da doença em poucos meses, podendo haver recorrência posterior; ou permanente quando, como o nome indica, não ocorre remissão. Ambas as condições são geneticamente heterogêneas; entretanto a maioria dos casos de DN transitório é decorrente de anormalidades da região de imprinted no cromossomo 6q24. Mutações ativadoras em heterozigose no gene KCNJ11, que codifica a subunidade Kir6.2 do canal de potássio ATP-sensível, são a causa mais comum de DN permanente. No presente artigo, discutimos as características clínicas do DN, os mecanismos moleculares envolvidos e suas implicações terapêuticas.

Neonatal diabetes is a rare condition characterized by hyperglycemia, requiring insulin treatment, diagnosed within the first months of life. The disorder may be either transient, resolving in infancy or early childhood with possible relapse later, or permanent in which case lifelong treatment is necessary. Both conditions are genetically heterogeneous; however, the majority of the cases of transient neonatal diabetes are due to abnormalities of an imprinted region of chromosome 6q24. For permanent neonatal diabetes, the most common causes are heterozygous activating mutations of KCNJ11, the gene encoding the Kir6.2 sub-unit of the ATP-sensitive potassium channel. In this article we discuss the clinical features of neonatal diabetes, the underlying genetic defects and the therapeutic implications.

Protection mechanisms of ATP-sensitive K channels on hippocampal CA1 neurons during chronic severe hypoxia / 中国应用生理学杂志

<p><b>AIM</b>To study the protection mechanisms of K(ATP) channels on hippocampal CA1 neurons during chronic severe hypoxia.</p><p><b>METHODS</b>p53 expression, DNA fraction, and cell apoptosis were examined in cultured hippocampal neurons in control group, hypoxia group, hypoxia group treated with K(ATP) channels antagonist and hypoxia group treated with K(ATP) channels agonist.</p><p><b>RESULTS</b>In the group of a 12 h long exposure to oxygen concentration of 0%, diazoxide (100 micromol/L), the K(ATP) channels agonist, reduced p53 expression and the hypoxia-induced apoptosis. In contrast, tolbutamide (100 micromol/L), the K(ATP) channels antagonist, significantly rose p53 expression and the hypoxia-induced apoptosis, which could be reversed by p53 inhibitor TSA.</p><p><b>CONCLUSION</b>K(ATP) channels protect hippocampal neurons against chronic severe hypoxia by suppressing p53 expression.</p>

The inhibition of CYP2C9 isoenzyme in Cunninghamella blakesleeana AS 3. 910 / 药学学报

<p><b>AIM</b>To investigate the variation of CYP2C9 isoenzyme activity in the microbial model in response to inhibitors of CYP2C9.</p><p><b>METHODS</b>Using C. blakesleeana AS 3. 910 as a model strain, the impact of CYP2C9 inhibitors on the metabolites yields of CYP2C9 substrates was determined and the drug-drug interactions among CYP2C9 substrates were evaluated. Liquid chromatography-mass spectrometry was used to analyze biotransformation products.</p><p><b>RESULTS</b>Benzbromarone decreased the yield of 4'-hydroxytolbutamide from 100% to 14.5%; sulfaphenazole decreased the yield of O-demethylindomethacin from 75.2% to 9.9%; valproic acid decreased the yield of 4'-hydroxydiclofenac from 98.6% to 2.7%, separately. Tolbutamide, indomethacin and diclofenac interacted with each other, resulting in the decreased formation of metabolites catalyzed by CYP2C9.</p><p><b>CONCLUSION</b>Three CYP2C9 inhibitors inhibit the activity of CYP2C9 isoenzyme in C. blakesleeana AS 3. 910 differently, and there are drug-drug interactions among CYP2C9 substrates.</p>

Influence of cytochrom P450 CYP2C9 polymorphism on the pharmacokinetics of tolbutamide metabolism using oligonucleotide genotyping microarray / 药学学报

<p><b>AIM</b>To investigate the influence of cytochrom P450 CYP2C9 polymorphism on the pharmacokinetics of tolbutamide.</p><p><b>METHODS</b>An oligonucleotide microarray was designed and fabricated to genotype the CYP2C9 accurately and quickly. 137 healthy volunteers were genotyped with the array to investigate the frequency of CYP2C9 functional SNPs. Moreover, 1 homozygous mutant, 9 heterozygous and 10 wild-genotypes subjects in the assay were selected randomly and sequenced directly. After orally taking tolbutamide, blood samples and urine samples were collected, and their pharmacokinetics was studied with HPLC.</p><p><b>RESULTS</b>CYP2C9 *1/*3 were found in 9 of 137 volunteers, CYP2C9 *3/*3 in only one, others were all CYP2C9 *1/*1 wild types. CYP2C9 *2, CYP2C9 *4 and CYP2C9 *5 alleles were not detected. Direct sequencing of the purified PCR products of the heterozygotes, mutant homozygotes and ten wild type individuals gave a corresponding result to that genotyped by microarray. Pharmacokinetic outcome showed that the individuals with CYP2C9 *1/*3 or CYP2C9 *3/*3 had slower metabolic elimination of tolbutamide than those with CYP2C9 *1/*1.</p><p><b>CONCLUSION</b>CYP2C9 genetic polymorphism has a significant influence on the pharmacokinetics of tolbutamide. Pharmacogenomic study will be helpful in guiding rational and individualized medication. Key words: tolbutamide; cytochrom P450 CYP2C9; allele; single nucleotide polymorphism; genotyping</p>

3T3-L1 adipocytes reduces Kir6.2 channel expression in MIN6 insulin-secreting cells in vitro / 生理学报

Dysfunction of the pancreatic beta-cell is an important defect in the pathophysiological changes of type 2 diabetes, and type 2 diabetes is evidently associated with obesity. But the role of the adipocyte in the dysfunction of the pancreatic beta-cell remains unknown. In the present study, we examined the direct effects of 3T3-L1 adipocytes on the expression of ATP-sensitive potassium channels (K(ATP) channels) in MIN6 insulin-secreting cells. MIN6 cells were divided into two groups as control group, where MIN6 cells were cultured in normal culture medium, and coculture group, where MIN6 cells were cocultured with differentiated 3T3-L1 adipocytes for 1 week. Semi-quantitative RT-PCR was employed to measure the expression of K(ATP) channel subunit Kir6.2 in MIN6 cells. Fura-2 was used to reflect changes in intracellular calcium concentration ([Ca(2+)](i)) in MIN6 cells. The secretary function of MIN6 cells from both groups was estimated by radioimmunoassay method. The results showed that the Kir6.2 cDNA levels corrected by GAPDH cDNA levels after densitometric analysis were 0.989+/-0.035 in control group and 0.726+/-0.087 in coculture group. The expression of Kir6.2 was significantly decreased in MIN6 cells in the coculture group as compared with that in control. MIN6 cells cocultured with 3T3-L1 adipocytes lost the ability to increase [Ca(2+)](i) when stimulated by tolbutamide (0.1 mmol/L), a highly selective KATP channel closer. In contrast, MIN6 cells in control group had typical responses to tolbutamide with a significant increase in [Ca(2+)](i). The magnitudes to basal levels of [Ca(2+)](i) after tolbutamide stimulation were 1.520+/-0.203 in control and 1.114+/-0.097 in coculture group (P<0.05, n=6). MIN6 cells in control showed a significant increase in insulin secretion from 0.38+/-0.099 mU/min to 2.87+/-0.248 mU/min after being stimulated by tolbutamide, whereas MIN6 cells in coculture group did not increase insulin secretion when stimulated by tolbutamide (0.21+/-0.055 mU/min to 0.22+/-0.082 mU/min). It is demonstrated that 3T3-L1 adipocytes decrease the expression of K(ATP) channels in MIN6 cells through secreting certain factors, which impair the secretary function of MIN6 cells. The present results indicate that adipocytes are directly involved in pancreatic beta-cell dysfunction, which may facilitate the development of type 2 diabetes.

Stability studies of tolbutamide/ß-cyclodextrin inclusion complexes

The ability of cyclodextrins to encapsulate many molcecules is used to improve the properties of drugs. Complexes of tolbutamide with ß-cyclodextrin were prepared by coprecipitation, kneading and freeze-drying. The inclusion complexes were stored under controlled conditions at 5ºC, 40ºC, 50ºC and 40ºC/75 per cent relative humidity. The influence of temperature and the humidity was examined by performing DSC thermal analysis, X-ray diffractometry, Raman spectroscopy and dissolution rate measurements. The results indicated that the interactions and dissolution rate of TBM/ß-CD inclusion complexes obtained by coprecipitation and kneading were unchanged after storage at 5ºC, 40ºC, 50ºC and 40ºC/75 per cent RH over six months...

Involvement of nitric oxide (NO) in hypoglycaemic activity of tolbutamide.

The study was conducted to find the involvement of Nitric Oxide (NO) using L-arginine, a NO precursor and NG-methyl L-arginine a nitric oxide synthase inhibitor on tolbutamide activity in normal rabbits. L-arginine (25-300 mg/kg, body weight, oral) produced transient and dose dependent hypoglycaemia. When combined with tolbutamide (40 mg/kg, oral) it produced early and prolonged action. The effect of tolbutamide was blocked by NG-methyl L-arginine (5 mg/kg, body weight, oral). The results confirm the involvement of NO in tolbutamide activity and the possibility of using L-arginine as a supplement to antidiabetic drugs in blood glucose control.

Experiencia clínica con un inhibidor de la alfa glucosidasa (acarbosa) en el tratamiento de la diabetes no insulinodependiente: estudio multicéntrico / Multicentric study on the effect of an alpha glucosidase inhibitor in the treatment of non insulin dependent diabetes

Diabetic patients received acarbose, 150 mg/day durign four weeks and this dose was increased to 300 mg/day durign 3 months. Afterwards, patients were followed for a period of 12 weeks without acarbose. Fasting and post-prandial blood glucose and glycosilated hemoglobin were measured sequentially durign the study. Results: Eighty five patients were recruited for the study but 64 complied with the treatment protocol. The age of these patients was 56 ñ 8.8 years old, their diabetes duration was 7.8 ñ 8.8 years and their body mass index was 27.6 ñ 3.6 kg/m². During acarbose treatment, glycosilated hemoglobin decreased from 8.36 ñ 1.33 to 7.71 + 1.7 percent (p < 0.001), fasting blood glucose decreased from 173 ñ 48 to 159 ñ 59 mg/dl (p < 0.03) and post-prandial blood glucose decreased from 254 ñ 80 to 241 ñ mg/dl (NS). After discontinuing acarbose glycosilated hemoglobin and blood glucose levels returned to basal levels. Body weight and blood pressure did not change during the treatment period. Fifty nine patients bad gastrointestinal symptoms (meteorism, flatulence and abdominal distention) that were mild in 59 percent and moderate in 39 percent. Episodes of hypoglycemia were not observed. Conclusions: Acarbose, associated to sylphonylureas is an effective drug to reduce blood glucose and glycosilated hemoglobin levels in patients with non insulin dependent diabetes

Effects of K+ channel modulators on extracellular K+ accumulation during ischemia in the rat hippocampal slice

Loss of synaptic transmission and accumulation of extracellular K+((K+)o) are the key features in ischemic brain damage. Here, we examined the effects of several K+ channel modulators on the early ischemic changes in population spike (PS) and (K+)o in the CA1 pyramidal layer of the rat hippocampal slice using electrophysiological techniques. After onset of anoxic aglycemia (AA), orthodromic field potentials decreased and disappeared in 3.3 +/- 0.22 min (mean +/- SEM, n = 40). The hypoxic injury potential (HIP), a transient recovery of PS appeared at 6.0 +/- 0.25 min (n = 40) in most slices during AA and lasted for 3.3 +/- 0.43 min. (K+)o increased initially at a rate of 0.43 mM/min (Phase 1) and later at a much faster rate (12.45 mM/min, Phase 2). The beginning of Phase 2 was invariably coincided with the disappearance of HIP. Among K+ channel modulators tested such as 4-aminopyridine (0.03, 0.3 mM), tetraethylammonium (0.1 mM), NS1619 (0.3 ~ 10 muM), niflumic acid (0.1 mM), glibenclamide (40 muM), tolbutamide (300 muM) and pinacidil (100 muM), only 4-aminopyridine (0.3 mM) induced slight increase of (K+)o during Phase 1. However, none of the above agents modulated the pattern of Phase 2 in (K+)o in response to AA. Taken together, the experimental data suggest that 4-aminopyridine-sensitive K+ channels, large conductance Ca2+/-activated K+ channels and ATP-sensitive K+ channels may not be the major contributors to the sudden increase of (K+)o during the early stage of brain ischemia, suggesting the presence of other routes of K+ efflux during brain ischemia.

Infuencia de la velocidad de la ingestion de la comida en la glucemia postprandial / The influence of speed on the ingestion of food in postpradina glucemia

Para valorar la influencia de la velocidad de la ingestión de la comida en la glucemia postprandial, se estudiaron a 10 voluntarios sanos y a 10 pacientes con diabetes mellitus no dependientes de insulina (DMNID). Todos ingirieron dos comidas idénticas (1890 J, carbohidratos 37 por ciento, proteínas 23 por ciento, lípidos 40 por ciento) en diferentes días. Una de las comidas fue ingerida en 10 minutos (ingestión rápida), la otra en 20 minutos (ingestión lenta). Se midieron los niveles de glucosa sérica inmediatamente antes de la comida y durante los siguientes 189 minutos. Los pacientes con DMNID tuvieron cifras de glucemia de los 30 a los 90 minutos significativamente mayores con la ingestión rápida que con la lenta. La máxima glucemia (MG) y el área bajo la curva de glucosa (ABC), también fueron significativamente mayores con la ingestión rápida: MG 15.8 ñ 4.3 y 12.9 ñ 2.6 mmol/L (XñSD) (p<0.05), ABC 13 ñ 2.4 y 11.3 ñ 2.9 mmol/L/h (p<0.05) con ingestión rápida y lenta respectivamente. En los individuos sanos no hubo diferencia entre las pruebas. La ingestión lenta de las comidas podría ser recomendable en los pacientes con DMNID.

Imágenes atípicas en aspergilosis pulmonar. Presentación de un caso / Atypical images in pulmonary asperglillosis. case report

Presentamos un caso de aspergilosis pulmonar atípico por su presentación radiológica, que puede resultar de interés tanto para el radiólogo como para el clínico, el tratamiento fue el habitutal, resaltan las imágenes por telerradiografía de tórax y por tomografía computada de tórax. Se describen las diferentes presentaciones radiológicas