Lactic acidosis,diabetes mellitus and the biguanide compounds

Summary After a brief outline of the factors regulating plasma lactate levels in normal and diabetic subjects, the AA. summarize the history, the possible mechanism of action and the therapeutic applications of the guanidine derivatives. The possibility that these drugs may increase the danger of lactic acidosis is discussed.

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Zusammenfassung Nach einer kurzen Schematisierung der Faktoren, welche die Laktatspiegel im Plasma normaler Personen und Diabetiker regeln, fassen die AA. die Geschichte, den moeglichen Wirkungsmechanismus und die therapeutischen Anwendungen der Guanidin-Derivate zusammen. Es wird die Moeglichkeit der Steigerung der Azidose-Periode (Milchsaeure) durch diese Arzneimittel diskutiert.

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Resumen Al cabo de breve esquema de los factores que regulan los niveles de lactato en el plasma de sujetos normales y diabéticos, los AA. resumen la historia, el modo de acción posible y las aplicaciones terapéuticas de los derivados de la guanidina. Se discute la posibilidad que estos fármacos puedan aumentar el período de la acidosis láctica.

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Resume Après un bref schème des facteurs qui réglent les niveaux du lactate dans le plasma des sujets normaux et diabétiques, les AA. résument l'histoire, le possible mécanisme d'action et les applications thérapeutiques des dérivés de la guanidine. On discute sur la possibilité que ces médicaments puissent accroître la période de l'acidose lactique.

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Riassunto Dopo un breve schema dei fattori che regolano i livelli di lattato nel plasma dei soggetti normali e diabetici, gli AA. riassumono la storia, il possibile meccanismo di azione e le applicazioni terapeutiche dei derivati della guanidina. Viene discussa la possibilità che questi farmaci possano incrementare il pericolo dell'acidosi lattica.

     

Differential expression of peroxisome proliferator activated receptor γ and cyclin D1 does not affect proliferation of asthma‐ and non‐asthma‐derived airway smooth muscle cells

Background and objective: Airway remodelling involves thickening of the airway smooth muscle (ASM) bulk. Proliferation of asthma‐derived ASM cells is increased in vitro, but underlying mechanisms remain unknown. Peroxisome proliferators activated receptor‐γ (PPARγ) regulates the cell cycle. It is suggested that PPARγ agonists have anti‐inflammatory effects, which may be valuable in the treatment of asthma, but information regarding their antiproliferative properties in ASM is lacking. Although corticosteroids reduce airway inflammation, in vitro they inhibit proliferation in only non‐asthma ASM cells by reducing cyclin D1. We therefore investigated the effects of mitogenic stimulation (foetal bovine serum (FBS)), and a PPARγ ligand (ciglitazone), on PPARγ and cyclin D1 expression and proliferation of ASM cells. In addition, we examined the effects of ciglitazone on ASM cell proliferation. Methods: We assessed PPARγ and cyclin D1 mRNA and protein levels using quantitative PCR and immunoblotting. Cell proliferation was assessed using bromodeoxyuridine uptake. Results: In the presence of 5% FBS, PPARγ and cyclin D1 expression decreased over time in non‐asthmatic cells but increased in asthmatic cells (compared with sub‐confluent cells). FBS‐induced proliferation of asthmatic cells increased at all time points, but occurred only at day 7 with non‐asthmatic cells (compared with unstimulated time‐matched control). Ciglitazone increased PPARγ expression in both groups, but did not alter cell proliferation, while fluticasone increased PPARγ protein only in asthmatic cells. Conclusions: Although in the presence of a mitogenic stimulus, PPARγ was differentially expressed in asthma‐ and non‐asthma‐derived ASM; its expression was not related to the increased proliferation observed in asthmatic ASM.     

Accuracy of computed tomographic intravenous cholangiography (CT-IVC) with iotroxate in the detection of choledocholithiasis

To determine the accuracy of computed tomographic intravenous cholangiography (CT-IVC) for detection of choledocholithiasis. Sixty-five patients undergoing endoscopic retrograde cholangiography (ERC) underwent CT-IVC prior to ERC, using a single detector helical CT following intravenous infusion of 100 ml iotroxate. Patients with bilirubin levels >3 times normal were excluded. ERC was indeterminate in three patients (4.7%) and CT-IVC in four (6.3%). Twenty-three patients had ductal calculi at ERC, and CT-IVC was positive in 22, with two false positives and one false negative: sensitivity 95.6%, specificity 94.3%. Stones were multiple in nine and solitary in 14. Of the 14 solitary stones, ten were 5 mm and eight were 4 mm. The bilirubin level in positive cases was within normal in 20. Maximum intensity projection (MIP) reformats showed stones in only 27% of cases and surface rendered (SR) reformats in none. CT-IVC is highly accurate for detection of ductal calculi, including single small calculi, with a normal or near normal serum bilirubin. Axial images should be used for interpretation rather than MIP or SR reformats.     

Refractive errors in infancy predict reduced performance on the movement assessment battery for children at 3 1/2 and 5 1/2 years

We have previously reported that significant hyperopia at 9 months predicts mild deficits on visuocognitive and visuomotor measures between 2 years and 5 years 6 months. Here we compare the motor skills of children who had been hyperopic in infancy (hyperopic group) with those who had been emmetropic (control group), using the Movement Assessment Battery for Children (Movement ABC). Children were tested at 3 years 6 months (hyperopic group: 47 males, 63 females, mean age 3 y 7 mo, SD 1.6 mo; control group: 61 males, 70 females, mean age 3 y 7 mo, SD 1.2 mo) and at 5 years 6 months (hyperopic group: 43 males, 56 females, mean age 5 y 4 mo, SD 1.7 mo; control group: 51 males, 62 females, mean age 5 y 3 mo, SD 1.6 mo). The hyperopic group performed significantly worse at both ages, overall and on at least one test from each category of motor skill (manual dexterity, balance, and ball skills). Distributions of scores showed that these differences were not due to poor performance by a minority but to a widespread mild deficit in the hyperopic group. This study also provides the first normative data on the Movement ABC for children below 4 years of age, and shows that it provides a useful measure of motor development at this young age.