Effects of Folic Acid and Folinic Acid on Pyrimethamine Teratogenesis in Rats

Abstract The effects of folic acid (FA) and folinic acid (FNA) on the teratogenicity of the antifolate drug pyrimethamine (PYR) were examined in rats. PYR and FA were orally administered with mashed feed. FNA was intraperitoneally injected. The drugs were administered for 5 days of day 11–15 of gestation. Six groups were made; G-I PYR 1.6 (mg/kg/day), G-II PYR 3.6, G-HI PYR 1.6 + FA 50, G-IV PYR 3.6 + FNA 12, G-V FA 50, G-VI control. No malformations were found in G-I, IV, V and VI. All fetuses in G-II and III had malformations. Main malformations in G-II and III were cleft palate and brachygnathia. Accordingly it might be demonstrated that the teratogenicity of PYR was potentiated by concurrent FA in rats.     

Inhibition of endocytosis activates alternative degradation pathway of βAPP in cultured cells

Background: Alzheimer’s disease associated βAPP is sequentially endoproteolyzed by α/β‐secretase and γ‐cleavage. In the process, extracellular shedding by α‐secretase (ADAM 9/10/17) or β‐secretase (BACE 1/2) at position L¹⁷ or D¹ (Aβ numbering) are prerequisites for the generation of P3 or Aβ, respectively. In addition, several alternative extracellular cleavage sites in βAPP have been reported at position I^?6, V^?3, R⁵, E¹¹, F²⁰, and A²¹. Among these sites, position R⁵ is considered to be cleaved by α‐secretase‐like activity, whereas position E¹¹, F²⁰ and A²¹ are cleaved by β‐secretase. Therefore, extracellular shedding of βAPP is thought to be mediated exclusively by α/β‐secretase activities. However, so far the characteristics of cleavages at position V^?3 and I^?6 are not well understood. The aim of this study is to characterize these two cleavages of βAPP. Methods: We analyzed the conditioned media of βAPP wt or sw expressing cells with or without pharmacological agents. Results: Here, we show that the cleavage at position I^?6 of βAPP has characteristics distinct from that of α/β‐secretase, while the cleavage at V^?3 seems to be mediated by β‐secretase. Although inhibition of endocytosis enhances the cleavages at both V^?3 and I^?6, PMA, an α‐secretase stimulator, treatment enhances neither of these cleavages. Interestingly, a β‐secretase inhibitor, z‐VLL‐CHO, suppressed V^?3 but not I^?6 cleavage. The pathological βAPP Swedish mutant adjacent to the cleavage sites shows similar effects. Conclusions: Our data demonstrate that neither α nor β‐secretase undergoes extracellular shedding at I^?6 of βAPP. Therefore, our data may indicate a novel alternative βAPP degradation pathway which is up‐regulated upon low level of endocytosis.     

Acute pancreatitis induced by hypercalcaemia associated with adult T-cell leukaemia: A case report

A 44 year old Japanese woman with adult T-cell leukaemia (ATL) was admitted to Kyushu University hospital to receive a course of α-interferon treatment. She experienced a sudden onset of hypercalcaemia and epigastric pain associated with an increase in the level of pancreatic enzymes. Her serum parathyroid hormone related protein level was above normal although her high sensitive PTH level was within the normal range. Ultrasonography and computed tomography (CT) of the abdomen showed enlargement of the pancreas with indistinct margins and massive accumulation of extrapancreatic fluid. Cullen's sign was observed. A few days after the onset of acute pancreatitis, the serum amylase level increased to 3400 IU/L, and the serum calcium level fell to 4.2 mg/dL from 13.3 mg/dL. Her fasting blood glucose level increased to 242 mg/dL. Although the first episode of pancreatitis appeared to respond to treatment, she experienced a second episode of pancreatitis accompanied by an elevation of the serum calcium level. These findings suggest that acute pancreatitis was caused by hypercalcaemia associated with ATL.     

Clinical Application of Transcutaneous Bilirubin Measurement

ABSTRACT. The purpose of this study was to investigate whether hyperbilirubinemia (15 mg/dl) could be predicted by TcB readings at birth or change of TcB readings during the first 24 hours of life. Both the TcB at 24 hours and the ratio of increase of TcB during the first 24 hours per kg birthweight were useful in predicting the development of hyperbilirubinemia (15 mg/dl). The test could be used as a noninvasive screening procedure to detect infants at risk for significant hyperbilirubinemia on the first day of life.     

SERUM ENDOGENOUS THYROXINE LEVELS IN MAN DURING ANAESTHESIA AND SURGERY

Determinations of serum thyroxine concentrations were made beforeinduction of anaesthesia, after 20 minutes and 40 minutes ofanaesthesia before operation, during operation, and after theend of operation in 36 patients. After 40 minutes of anaesthesiawith diethyl ether and halothane there were significantly increasedendogenous serum thyroxine concentrations, but thiopentone,nitrous oxide and oxygen anaesthesia definitely decreased thethyroxine level. Surgical operation further elevated the serumthyroxine level in both ether and halathane anaesthesia groupsbut no significant rise of thyroxine levels was observed inthe thiopentone, nitrous oxide and oxygen groups.