Biophysical studies and anti‐growth activities of a peptide,a certain analog and a fragment peptide derived from α‐fetoprotein

Abstract: A chemically synthesized 34‐amino acid peptide, an analog, and a fragment of the peptide have been purified and studied. Biophysical studies were carried out to determine some of the metal ion binding properties of the original peptide and an analog of this parent peptide, in which the two histidine residues were replaced by alanines. As shown by visible absorption spectroscopy, Co (II) forms a complex with the parent peptide, but not with the analog peptide, and one or two histidines in the parent peptide are ligands for Co (II) ion binding. The effects on disulfide bond formation in the peptide by Zn (II) and Co (II) ions were also examined for this analog. Anti‐growth assays were performed using the original cysteine‐containing peptide with Zn (II) ion complexed to the peptide through the two cysteine residues. These rat uterine growth assays showed that the complexing of Zn (II) ion to the peptide maintained the anti‐growth activity of the peptide, while gel‐filtration experiments showed the zinc ions maintained the peptide in its anti‐growth form indefinitely in solution. A saliently important part of this research was the discovery that a fragment of the peptide consisting of a middle sequence of 14 amino acids was found to have significant anti‐growth activity in the rat uterine assay. Its activity suggested that this fragment might be considered a viable candidate for testing in anti‐cancer protocols.     

Interaction between mothers and infants born at risk during the first six months of corrected age

Abstract The effects of preterm birth and the perinatal infant health condition on mother-infant interactions were analysed in 278 mother-infant pairs, divided into four groups according to infants' gestational age at birth: group 1. 23–31 weeks; group 2,32–36 weeks; group 3, 37–42 weeks; and group 4, a control group of healthy full-term infants. The methodological approach was based on observation of the pairs at 2,4 and 6 months of infants" corrected age (± 1 week) during undressing of the infant and face-to-face interaction. It was found that mother-infant pairs with preterm infants (groups 1 and 2) did not differ in interactional variables from those of the control group. On the other hand, the birth of a full-term infant in need of neonatal intensive care (group 3) affected maternal and infant interactive behaviour. Additionally, infants from group 3 did not show stability in their interactive behaviour between any ages of measurement. This result suggests that interactive behaviour of full-term infants in need of neonatal intensive care are rather unpredictable during their first 6 months of life, which might have contributed to the less optimal interactive pattern observed for their mothers compared with mothers of the control group.     

Pharmacokinetic study of low- versus high-dose medroxyprogesterone acetate (MPA) in women

The present study was conducted to compare the pharmacokinetics (PK) of low-dose versus high-dose medroxyprogesterone (MPA) as a once-daily oral administration. Of 32 patients, all women, enrolled in this PK study, 18 received 600 mg MPA daily and 14 received 1200 mg daily. Detailed PK data were obtained on day 1 and after more than 4 weeks of MPA treatment. In addition, multiple data for the minimum steady-state concentration (Css min) were analyzed. The MPA serum concentrations were measured by high-performance liquid chromatography. Wide interpatient variability was found in the PK parameters obtained both on day 1 and after more than 4 weeks. There were no clear relationships between the oral dose and the MPA peak concentration (Cmax), area under the time versus concentration curve (AUC), or mean Css min. Weight gains of 10% or more were demonstrated more frequently in the high-dose group (P<0.01). Liver dysfunction (n=5) did not influence the PK of MPA. Five patients demonstrated extremely low AUC and Cmax (<10 ng/ml) values on day 1. Phenobarbital, dexamethasone and betamethasone were being taken concomitantly with the MPA each by one patient. The serum MPA concentrations were markedly increased after the discontinuation of phenobarbital in that patient, suggesting a drug interaction. At present we cannot recommend the high dose of MPA, except in clinical studies, from a PK or a pharmacodynamic points of view. Received: 2 May 1997 / Accepted: 13 October 1997     

Medial prefrontal transection enhances social interaction. II: neurochemical studies

Medial prefrontal cortex (MPFC) transection enhances social interaction in an open arena test. Social interaction enhances dopaminergic activity in the nucleus accumbens (NAC). In the present set of experiments, microdialysis probes were implanted in the NAC, and glutamate, gamma-aminobutyric acid (GABA) and dopamine (DA) were measured during electrical stimulation of the MPFC, after coronal transection caudal to the MPFC and after a systemic injection of amphetamine in transected rats. Electrical stimulation of the MPFC caused a transient enhancement of glutamate release in the NAC, no change in GABA levels and a long lasting increase in DA levels. Medial prefrontal transection did not change basal glutamate or GABA levels in the NAC, but increased basal DA levels. Amphetamine administration decreased GABA levels in medial prefrontal transected rats, had no effect on glutamate and increased DA levels more than in controls. The experiments suggest that glutamatergic activity in the accumbens decreases dopamine release. Medial prefrontal transection reduces glutamatergic tone and enhances dopamine release, which probably decreases GABAergic activity in the NAC. Presumably, GABA inhibition in the NAC enhances social interaction.     

Male mice lacking the gastrin-releasing peptide receptor (GRP-R) display elevated preference for conspecific odors and increased social investigatory behaviors

Previously, we generated gastrin-releasing peptide receptor null mutant mice (GRP-R-deficient mice), and found that these animals displayed increased non-aggressive social responses in an ordinary social interaction test using a resident-intruder method. In the present study, we examined in more detail the social behaviors of GRP-R-deficient male mice. In social interaction tests, GRP-R-deficient mice showed more social responses, such as sniffing and nosing, relative to wild-type mice, and similar results were obtained whether GRP-R-deficient mice served as intruders or residents. In the same way, they showed more contact behaviors toward an anesthetized conspecific, and less locomotor activity than wild-type mice in a social investigation test toward an anesthetized male mouse. Since olfactory systems play important roles in the social behavior of rodents, olfactory preference tests were conducted in order to evaluate the olfactory properties of GRP-R-deficient mice. The results suggest that no differences exist between wild-type mice and GRP-R-deficient mice in the preference between a novel sawdust odor and their own odor, or that of other male mice. However, GRP-R-deficient mice preferred the odor of other male mice to their own, in contrast to wild-type mice. Furthermore, the preferences of GRP-R-deficient and wild-type mice were not disrupted by intraperitoneal infusion of diazepam (1.5 mg/kg). These results indicate that neither the motion, nor the behavior of conspecifics, nor reduced anxiety lead to the increased non-aggressive social responses and/or social investigatory behaviors in GRP-R-deficient mice. Rather, these latter behaviors may be a consequence of altered cognition of conspecific odors in the mutant mice.     

Treatment of refractory complex-partial status epilepticus with propofol: case report

PURPOSE: We report a case of a 65-year-old woman who had a subarachnoid and intraventricular hemorrhage secondary to rupture of an anterior communicating artery aneurysm and developed nonconvulsive status epilepticus of the complex-partial type, refractory to phenytoin (PHT), phenobarbital (PB), valproate (VPA), and lorazepam (LZP). METHODS: Three weeks after diagnosis of nonconvulsive status epilepticus, general anesthesia was induced with propofol and titrated to burst suppression on the electroencephalogram (EEG). RESULTS: During propofol infusion, the serum VPA level declined markedly, and despite >3 g daily doses, did not return to the therapeutic range, until several days after propofol was discontinued. Continuous propofol infusion was stopped after 7 days, and the patient recovered consciousness. Despite further complications, she gradually regained normal function and was discharged home 4 months after surgery. CONCLUSIONS: This is the first case of nonconvulsive status epilepticus successfully treated with propofol.     

Marked enhancement of anti-allodynic effect by combined intrathecal administration of the adenosine A1-receptor agonist R-phenylisopropyladenosine and morphine in a rat model of central pain

BACKGROUND: There is often no satisfactory treatment for chronic pain after spinal cord injury. We have previously reported that intrathecal (i.t.) administration of the adenosine A1-receptor agonist R-phenylisopropyl-adenosine (R-PIA) or the opioid morphine has anti-allodynic effects in a model of presumed chronic central pain after photochemically induced spinal cord injury in rats. In the present study, we set out to investigate the possible interaction between i.t. R-PIA and morphine in spinally injured rats. METHODS: Sprague-Dawley rats displaying allodynia-like behaviors to mechanical and cold stimuli after photochemically induced spinal cord injury with minor motor deficits were used. R-PIA and morphine, either alone or in combination, were administered i.t. through an implanted catheter to lumbar spinal cord. RESULTS: Cumulative doses of R-PIA or morphine dose-dependently reduced the mechanical allodynia-like behavior, with a threshold of 1 nmol and 1.5 nmol, respectively. When co-administrated, R-PIA and morphine produced marked suppression of mechanical allodynia at doses of 5 pmol and 7.5 pmol, respectively. The effect of i.t. co-administration of R-PIA and morphine on cold allodynia was comparable to i.t. R-PIA alone. The combination of R-PIA and morphine did not increase adverse effects such as motor deficits in comparison to either drug alone. CONCLUSION: These results demonstrate a supra-additive interaction between the adenosine A1-receptor agonist R-PIA and morphine to reduce mechanical allodynia-like behavior in rats with chronic spinal cord injury. The combination of R-PIA and morphine administered spinally may be superior to R-PIA or morphine alone for treating such pain.     

环境危险因素和代谢酶基因多态性与白血病关系的研究

[目的]研究环境危险因素和代谢酶基因多态性及其交互作用与白血病发生的关系。[方法]通过1：1配对病例-对照研究，对用药史、家居附近三废污染、职业暴露史、家居装潢史、吸烟史、染发史等相关因素进行调查；同时运用PCR技术，检测病例与对照的CYP1A1、GSTT1、GSTM1基因型，并分析基因．环境之间的交互作用。[结果]暴露染发年限(OR：2．182，95％CI：1．224～3．828)和装修后入住间隔(OR：1．665，95％CI：1．069～2．529)是白血病发生的危险因素；CYP1A1突变型(P=0．0235)与GSTT1缺失型基因(P=0．0042)可能增加患白血病的危险，而且与染发史或装修史存在交互作用。[结论]暴露干染发或装修，同时存在CYP1A1突变型基因或GSTT1缺失型基因可能增加白血病发生的危险性。     

MATERNAL ANEMIA AND POSTPARTUM WEIGHT CHANGE ASSOCIATED WITH DECREASED MATERNAL-INFANT INTERACTION IN A RURAL KENYAN POPULATION

Associations between maternal nutritional factors including energy intake, body mass index, postpartum weight change, and anemia status and maternal-infant interactions were examined in 124 mother-infant pairs from a marginally malnourished, rural Kenyan population. Anemic mothers spent less time holding and caring for their infants than nonanemic mothers. Mothers who retained their pregnancy weight gain or were able to gain weight postpartum spent more time looking at their infants than mothers who lost weight postpartum. Maternal food intake per se was not associated with patterns of infant interaction. Lower birth weight infants were held more, cared for more, and looked at face-to-face more by their mothers. Older sisters tended to be more involved in infant interactions with higher birth weight infants.     

eNOS基因变异与超重对早发冠心病的影响

目的探讨内皮型～氧化氮合成酶(eNOS)基因第7外显子G894T(Glu298Asp)变异与超重交互作用对早发冠心病的影响。方法采用以医院为基础的病例对照研究方法，选择新诊断的冠心病患者为研究对象；男性55岁以前及女性65岁以前患冠心病为早发冠心病；以132例早发冠心病患者为病例，172例迟发冠心病患者为对照组。运用PCR-限制性片段长度多态性检测G894T变异；用相加模型分析G894T变异与超重的交互作用。结果G894T变异与超重之间对早发冠心病具有正交互作用，协同效应指数(S)为1．45；交互效应超额相对危险度(RERI)为1．32；归因交互效应百分比(AP)为25．06％。用多元Logistic回归调整性别、吸烟、饮酒、腰臀比、甘油三酯、总胆固醇后，G894T变异与超重之间对早发冠心病仍具有正交互作用。调整上述混杂因素后，S为1．43；RERI为2.76；AP为27．21。结论eNOS基因G894T变异与超重在早发冠心病的患病中存在明显的正相加模型交互作用，使早发冠心病患病危险性增加近3倍；G894T变异与超重同时存在时，早发冠心病患病危险性中约27％是由于两者交互作用所导致。