Assessment of value of glycosylated albumin and protein in detection of gestational diabetes

There is a recognized need for the early detection of gestational diabetes, and a single blood test, if reliable, would be advantageous. Because serum albumin and total protein are glycosylated and have short life spans, we investigated the usefulness of glycosylated albumin and glycosylated protein in the detection of gestational diabetes. We studied five groups, each with 20 subjects: nonpregnant and pregnant controls, nonpregnant and pregnant insulin-dependent diabetic (IDDM) patients, and gestational diabetic patients. All patients with no history of diabetes had an oral glucose tolerance test to define their carbohydrate status. Our results showed that percent glycosylated albumin and percent glycosylated protein were significantly elevated in both groups of IDDM patients compared with the other groups. However, gestational diabetic patients had glycosylated albumin and glycosylated protein values similar to those of both control groups. Both glycosylated albumin and glycosylated protein correlated well with HbA1c determinations. Thus, glycosylated albumin and glycosylated protein may be a good index of glycemic control, but they are of little value in the diagnosis of gestational diabetes because of a lack of sensitivity: 8 and 3% for glycosylated albumin and glycosylated protein, respectively.     

Inhibition and reversal of platelet-rich arterial thrombus in vivo: direct vs. indirect factor Xa inhibition

BACKGROUND/OBJECTIVE: The efficacy of a direct factor (F)Xa inhibitor, ZK-807834, was compared with indirect inhibition by enoxaparin for inhibition and deaggregation of acute platelet-rich thrombi in a well-characterized porcine carotid injury model. METHODS: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 min. Pigs then received intravenous drug for 35 min: ZK-807834-Dose 1 (40 microg kg(-1) bolus + 1.5 microg kg(-1) min(-1) infusion, n=6); ZK-807834-Dose 2 (20 microg kg(-1) bolus + 0.75 microg kg(-1) min(-1) infusion; n=6); enoxaparin (1 mg kg(-1) bolus; n=6); or saline (n=6). Five minutes after drug initiation, the contralateral artery was injured. Thrombus size was monitored by scintillation detection of autologous 111In-platelets. RESULTS: The prothrombin time ratio was 2.2 +/- 0.1; 1.4 +/- 0.3; 1.2 +/- 0.9 and 1.1 +/- 0.2, respectively. ZK-807834-Dose 1 significantly inhibited carotid platelet deposition (525 +/- 226 x 10(6) cm(-2); P = 0.008), whereas ZK-807834-Dose 2 (2325 +/- 768) and enoxaparin (1236 +/- 383) were not different from saline (2776 +/- 642). Thrombus deaggregation was greatest for animals receiving ZK-807834-Dose 1 (473 +/- 185). Neither ZK-807834-Dose 2 (1588 +/- 480) nor enoxaparin (1618 +/- 686) was different from saline control (2222 +/- 598). CONCLUSIONS: Direct FXa inhibition with ZK-807834, at a prothrombin time ratio of 2.2, effectively inhibits thrombosis and promptly deaggregates thrombi induced by arterial injury. In contrast, indirect FXa inhibition with enoxaparin was ineffective.     

Developmental Toxicity of Dimethylacetamide by Inhalation in the Rat

Developmental Toxicity of Dimethylacetamide by Inhalation inthe Rat. SOLOMON, H. M., FERENZ, R. L., KENNEDY, G. L., ANDSTAPLES, R. E. (1991). Fundam. Appl. Toxicol. 16, 414–422.Dimethylacetamide (DMAC) is a widely used industrial solvent.It has been reported to be teratogenic when given to rats byinjection or following dermal application. Most of these studiesemployed large single doses and did not examine both the fetaland the maternal response. In this study, groups of pregnantCrl:CD rats were exposed to 32, 100, or 282 ppm DMAC by inhalationfor 6 hr/day from Days 6 through 15 of gestation (day on whichcopulation plug was detected was termed Day 1G). A control groupof chambered pregnant rats was exposed simultaneously to aironly. All female rats were euthanized on Day 21G. At 282 ppm,both maternal weight gain during the exposure period and fetalweight were significantly decreased and accompanied by a significantdose-response trend. These effects were not seen in rats inhalingeither 32 or 100 ppm. Fetal resorptions were not increased inany of the groups exposed to DMAC. Fetal incidences of external,visceral, or skeletal variations and malformations were similarbetween the test and control groups. Therefore, both fetal andmaternal toxicity were noted at 282 ppm and the no-observedadverse-effect level under these experimental conditions was100 ppm for both the dam and the conceptus. DMAC was not demonstratedto produce malformations in the rat fetus even at a level thatwas toxic to the dam.     

Direct cadiac electorphysiologic effects of sufentanil and vecuronium in isolated guinea-pig hearts

Sufentanil and vecuronium are commonly used simultaneously in anaesthesia. Bradycardia and asystole have been described immediately after the administration of these two compounds. Therefore, the purpose of the present study was to evaluate the direct cardiac effects of sufentanil and vecuronium in all parts of the cardiac pacemaker and conduction system.
The electrophysiological effects of sufentanil and vecuronium were studied in isolated spontaneously beating guinea-pig hearts perfused by the method of Langendorff. At a concentration of 0.1 μmol/1 sufentanil a significant reduction of the spontaneous sinus rate, prolongation of atrioventricular, intraventricular and His' bundle conduction could be observed. The highest concentration of 10 μmol/1 of sufentanil led to an overall slowing of conduction velocity and to an profound slowing of spontaneous sinus rate. AV nodal as well as atrial and ventricular refractoriness were markedly prolonged at this high concentration of sufentanil. In contrast, during perfusion with vecuronium at a concentration of 0.1 μmol/1 up to 10 μmol/1 no significant effects on cardiac conduction and pacemaker activity could be observed.
In conclusion, the electrophysiological effects of sufentanil are comparable to that of unspecific calcium antagonists. Therefore, especially in patients with a preexisting damage of the cardiac conduction system, the indirect effect of the combination of sufentanil and vecuronium which is predominantly responsible for bradycardia and asystole may be worsened by the direct effects of sufentanil.     

The effects of LY-201116 [4-amino-N-(2,6-dimethylphenyl) benzamide] on the amygdala-kindled rat

The effects of LY-201116, a 4-aminobenzamide, were examined in rats using the amygdala kindling model, both during acquisition of the kindled response and in fully kindled animals. Dose-response and time-response studies for efficacy and rotorod toxicity were completed following intraperitoneal injection of the drug. Afterdischarge duration, behavioral seizure response, kindled seizure threshold and EEG recordings were used to assess efficacy and toxicity of the drug. In the acquisition trial, the drug (7.5 mg/Kg) did not significantly alter the number of stimulations required to produce the first stage 5 kindled response nor did it modify afterdischarge durations. Doses of 11.25 and 15 mg/Kg suppressed afterdischarge and diminished behavioral responses significantly in fully kindled rats, but these doses were also neurotoxic as judged by rotorod performance. The non-selective anticonvulsant effect of 11.25 mg/Kg lasted at least 90 min. A dose of 15 mg/Kg raised kindled seizure threshold and diminished afterdischarge duration. Doses of 20, 30 and 40 mg/Kg produced spontaneous EEG spikes and seizures accompanied by behavioral convulsions. The drug thus exhibited non-selective anticonvulsant effects in fully kindled rats following doses of 11.25 or 15 mg/Kg, but exhibited proconvulsant activity following doses in the range of 20-40 mg/Kg.