Diet and phenylketonuria: time for change?

This article is a report of a meeting of dietitians held on 15 September 1992 in Birmingham to discuss the recommendations of a 'Medical Research Council Working Party on the Dietary Management of Phenylketonuria'. (Contributions on the day of the meeting came from Judith Houghton, Eleanor Weetch, Isabel Smith, Sheena Laing, Ruth Watling, John Walter, Rodney Pollitt.)     

Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses,linearity and plasma protein binding

The pharmacokinetics of reboxetine, a new antidepressant agent, were found to be close to linear in a crossover study comparing administration of single 2, 3, 4 and 5 mg capsule doses in 15 healthy male volunteers, and in the same study the capsules were bioequivalent to the proposed therapeutic tablet formulation (4mg). Kinetic analysis was based on HPLC assay of reboxetine in plasma and urine collected up to 72 h after each administration. Plasma levels indicated a rapid absorption (t_max?2h) and an elimination half-life of about 13 h. Clearance and volume of distribution were modest (ratios to bioavailability: CL/F?29 mL min^?1; V_z/F?32L); urinary excretion was ～9% of dose, corresponding to a renal clearance of only 3 mL min^?1 (a value consistent with the rate of glomerular filtration of unbound drug). In vitro, binding to plasma proteins, estimated from radioactivity levels following dialysis of ¹⁴C-labelled reboxetine, appeared to be dominated by α₁-acid glycoprotein without marked saturation up to plasma concentrations of over 500 ng mL^?1 (2.8–3.1% unbound with human plasma from three additional volunteers; 1.8–2.0% for 2gL^?1 orosomucoid α₁-acid glycoprotein, and 46.4–47.4% for 40 gL^?1 albumin), whilst the mean C_max in the current study was much lower (164 ng mL^?1 after a 5 mg dose).     

Differential effects of luminol,nickel, and arsenite on the rejoining of ultraviolet light and alkylation-induced DNA breaks

When Chinese hamster ovary cells were treated with ultraviolet (UV) light or methyl methanesulfonate (MMS), a large number of DNA strand breaks could be detected by alkaline elution. These strand breaks gradually disappeared if the treated cells were allowed to recover in a drug-free medium. The presence of nickel or arsenite during the recovery incubation retarded the disappearance of UV-induced strand breaks, whereas the disappearance of MMS-induced strand breaks was retarded by the presence of arsenite or of luminol, a new inhibitor for poly(ADP-ribose) synthetase. Luminol, however, had no apparent effect on the repair of UV-induced DNA strand breaks, and nickel had no effect on the repair of MMS-induced DNA strand breaks. When UV- or MMS-treated cells were incubated in cytosine arabinofuranoside (AraC) plus hydroxyurea (HU), a large amount of low molecular weight DNA was detected by alkaline sucrose sedimentation. The molecular weight of these DNAs increased if the cells were further incubated in a drug-free medium. This rejoining of breaks in cells pretreated with UV plus AraC and HU was inhibited by nickel and by arsenite, but not by luminol. The rejoining of breaks in cells pretreated with MMS plus AraC and HU was inhibited by luminol and by arsenite, but not by nickel. These results suggest that different enzymes may be used in DNA resynthesis and/or ligation during the repairing of UV- and MMS-induced DNA strand breaks, and that nickel, luminol, and arsenite may have differential inhibitory effects on these enzymes. © 1994 Wiley-Liss, Inc.     

Fractionation of a chalone-containing preparation from Ehrlich's ascites tumor by high performance liquid chromatography

Department of Biology, Medico-Biological Faculty, and Applied Research Laboratory of Ecology, Toxicology, and Metabolism of Medicinal Preparations, attached to the Department of Biochemistry, Medico-Biological Faculty, N. I. Pirogov Second Moscow Medical Institute. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 10, pp. 418–419, October, 1991.     

Protein C concentrate prevents peripartum thrombosis.

A protein C deficient woman, with a past history of recurrent thrombosis and purpura fulminans, was successfully treated with protein C concentrate in the peripartum period. © 1992 Wiley-Liss, Inc.     

褪黑素对急性胰腺炎相关性肺损伤中趋化因子MIP-2表达的影响

目的观察褪黑素(MT)对ANP大鼠肺组织趋化因子巨噬细胞炎性蛋白-2(MIP-2)表达的影响,探讨MIP-2在ANP相关肺损伤发病机制中的作用。方法35只SD大鼠随机分为假手术组(SO组),ANP 3h、6h、12h组和MT 3h、6h、12h组,每组5只。采用4%牛磺胆酸钠胰胆管逆行注射制备ANP动物模型,MT组在ANP诱导前30min腹腔注射MT 20mg/kg体重。检测血淀粉酶,观察肺组织病理学改变,采用实时定量RT-PCR法和免疫组化检测肺组织中MIP-2 mRNA和蛋白的表达。结果与SO组相比,ANP 3h、6h和12h组肺组织MIP-2 mRNA表达分别增加48%,137%和230%。ANP组MIP-2蛋白表达量分别为3.40±0.84,5.80±0.55和6.40±0.45。MT干预组肺组织损伤得到改善,MIP-2 mRNA表达分别为ANP相应时间点的87%,77%和84%,MIP-2蛋白表达分别为2.20±0.84.4.20±0.45和5.20±0.50,与ANP相应时间点比较,相差显著(P<0.05)。结论MIP-2在ANP相关肺损伤发病中起一定作用,MT可能通过下调MIP-2的表达以减轻ANP相关肺损伤的程度。     

嗜酸性粒细胞阳离子蛋白测定的影响因素探讨

目的探讨温度、抗凝剂(EDTA-K2)对血嗜酸性粒细胞阳离子蛋白(ECP)水平的影响。方法采用固相双位点酶放大化学发光法,分别对22例健康体检者在两种不同温度(25℃和37℃)的血清标本,以及在相同温度(37℃)下,加抗凝剂和不加抗凝剂的血标本进行ECP水平测定。结果25℃组和37℃组血清ECP水平分别为8.92±6.45μg/L(x±s)和19.87±12.16μg/L(x±s),两组有显著性差异(P<0.01);37℃温度下加抗凝剂和不加抗凝剂血标本的ECP水平分别为5.26±2.60μg/L(x±s)和19.87±12.16μg/L(x±s),两组也有显著性差异(P<0.001)。结论温度和抗凝剂(EDTA-K2)对血标本的ECP水平测定有不同程度的影响。     

A rare polymorphism affects a mitogen-activated protein kinase site in synapsin III: possible relationship to schizophrenia.

BACKGROUND: Synapsin III plays a role in neuronal plasticity and maps to chromosome 22q12-13, a region suggested to be linked to schizophrenia. To determine if synapsin III plays a role in this disease, we searched for polymorphisms in this gene in patients with schizophrenia and controls. METHODS: The synapsin III gene was initially sequenced from 10 individuals with schizophrenia to identify polymorphisms. Association analysis was then performed using 118 individuals with schizophrenia and 330 population controls. Synapsin III expression was studied by immunoblot analyses, and phosphorylation sites were mapped by sequencing trypsin-digested synapsin III fragments phosphorylated with phosphorus-32. RESULTS: A rare, missense polymorphism, S470N, was identified in the synapsin III gene and appeared more frequently in individuals with schizophrenia than in controls (p =.0048). The site affected by the polymorphism, Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action. Phosphorylation at Ser470 was increased during neonatal development and in response to neurotrophin-3 in cultured hippocampal neurons. CONCLUSIONS: Our observations suggest an association of a rare polymorphism in synapsin III with schizophrenia, but further studies will be required to clarify its role in this disease.     

PRKCG mutation (SCA-14) causing a Ramsay Hunt phenotype.

Progressive myoclonic ataxia, also referred to as Ramsay Hunt syndrome, is characterized by a combination of myoclonus and cerebellar ataxia, infrequently accompanied by tonic-clonic seizures. Its differential diagnosis overlaps with progressive myoclonic epilepsy, a syndrome with myoclonus, tonic-clonic seizures, progressive ataxia and dementia. In patients with progressive myoclonic epilepsy, specific diseases can frequently be recognized, but the diagnostic yield in progressive myoclonic ataxia is much lower. We describe a patient who presented with multifocal myoclonus in his thirties and who later developed cerebellar ataxia and focal dystonia. His father was similarly affected. Genetic studies revealed a mutation in the protein kinase C gamma (PRKCG) gene, known to cause spinocerebellar ataxia type 14 (SCA-14). This case illustrates that both myoclonus and dystonia are part of the clinical spectrum in SCA-14 and that myoclonus can even be the presenting symptom. We suggest that SCA-14 should be considered in the differential diagnosis of progressive myoclonic ataxia.