The Antley-Bixler syndrome is a rare disorder characterized by craniosynostosis, midface hypoplasia, radiohumeral synostosis, joint contractures, arachnodactyly, and femoral bowing and fractures. We report four cases with this disorder, all of which had craniosynostosis, midface hypoplasia with characteristic facial appearance, and contractures of bilateral elbow joints. However, femoral bowing, fractures, and arachnodactyly were not seen in our patients. In addition, proximal phalanges of the thumb and the great toe showed deformity of the delta phalanx in two cases. Characteristic features in these cases were the synostotic deformity of the elbow joint; three had radioulnahumeral synostosis, and one had radioulnar synostosis. Therefore, our cases indicated that various synostotic patterns of the elbow joints may exist in this syndrome. It is reasonable to propose that characteristic craniofacial appearance associated with the synostosis of the elbow joints of various forms should be considered minimal diagnostic criteria of the Antley-Bixler syndrome.

Child, Preschool↗

PubMedDate not supplied

Pharmacological studies on the hypoglycemic effect of 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H-thi opyrano [3,2-d] pyrimidine dimaleate (MTP-1307), a novel hypoglycemic agent.

MTP-1307, 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H- thiopyrano[3,2-d]pyrimidine dimaleate, is a novel oral hypoglycemic agent, structurally different from any existing hypoglycemic drugs. In fasted rats, the hypoglycemic effect of MTP-1307 was accompanied by elevation of the plasma insulin. In glucose tolerance tests, MTP-1307 suppressed the hyperglycemia after glucose loading and significantly enhanced the glucose-induced insulin secretion. In isolated hepatocytes from fasted rats, MTP-1307 inhibited gluconeogenesis from lactate and alanine. Furthermore, MTP-1307 increased the lactate/pyruvate ratio but did not increase the lactate level. MTP-1307 did not influence glycogenolysis in isolated hepatocytes from fed rats. In genetically diabetic ob/ob mice, MTP-1307 decreased the blood glucose level and improved glucose tolerance, but did not affect the level of plasma insulin. MTP-1307 increased 14CO2 production from glucose in isolated epididymal fat pads of ob/ob mice. Thus, these findings suggest that MTP-1307 produces hypoglycemic activities not only in normal animals but also in genetically diabetic animals, and that the hypoglycemic mechanism of MTP-1307 involves the promotion of glucose utilization in adipose tissue and, partially, the inhibition of gluconeogenesis in the liver and the stimulation of insulin release from the pancreas.

Adipose Tissue↗

PubMedDate not supplied

Antiparkinsonian effects of BAM-1110, a novel ergoline derivative, in MPTP-treated cynomolgus monkeys.

BAM-1110 [(5R,8R,10R)-6-methyl-8-(1,2,4-triazol-l-ylmethyl) ergoline maleate] is a newly synthesized dopamine agonist that produces little anorexic side effects (nausea and vomiting). The current study examines the effects of BAM-1110 on parkinsonian symptoms in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, an animal model of Parkinson's disease. First, a significant antiparkinsonian effect of apomorphine hydrochloride (0.3 mg/kg given subcutaneously) was confirmed in these animals. BAM-1110 (0.1, 0.3, and 1 mg/kg subcutaneously) relieved parkinsonian symptoms in a dose-dependent manner. Significant effects were observed at doses of 0.3 and 1 mg/kg and lasted for at least 3 h. BAM-1110, at a dose of 0.3 mg/kg that produced the submaximal antiparkinsonian effect, did not induce significant abnormal behaviors such as hyperactivity and stereotyped behaviors. Significant stereotyped behaviors were observed at 1 mg/kg of BAM-1110. Apomorphine induced hyperactive and stereotyped behaviors in parallel with its antiparkinsonian effect. BAM-1110 appears to be a potentially useful dopamine agonist to treat Parkinson's disease because of its relatively weak drug-induced hyperactive disturbances and anorexic side effects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗