Intestinal absorption, metabolism and effects of bacterial chemotactic peptides in rat intestine

N -formylated chemotactic peptides are produced by intestinal bacteria in vitro and Can be detected in intestinal luminal fluids. The healthy intestine must have mechanisms for preventing absorption of such peptides which can induce an inflammatory response when introduced systemically. Synthetic formyl-methionyl-leucyl-phenylalanine ( F -met-leu-³H-phe) has been used as a model bacterial chemotactic peptide to investigate intestinal absorption and metabolism of such peptides in the rat. Disappearance of tritium-activity was rapid from jejunal and ileal loops and substantial hydrolysis of peptide occurred with only labelled metabolites appearing in portal blood. Less absorption and less metabolism occurred in the colon. Degradation of F -met-leu-phe was due to a mucosal carboxypeptidase and was inhibited by benzylsuccinate, a potent inhibitor of the enzyme. In the presence of inhibitor, luminal disappearance from ileal loops was abolished and F -met-leu-³H-phe was not detected in portal blood indicating that healthy gut mucosa is 'impermeable' to intact peptide. The intestinal 'barrier' preventing mucosal penetration and the inflammatory effects of luminal bacterial peptides have two components: restricted mucosal permeability and a carboxypeptidase capable of hydrolysing such peptides with loss of their bioactivity.     

A new detector for fully automatic peptide synthesis

A new method of monitoring the rate of reactions in solid phase peptide synthesis is described. A conductivity detector in the reaction cell enables the deprotection, washing, and subsequent coupling stages to be examined in detail. The half lives of the reactions can be calculated and hence the optimum reaction times predicted. The aggregation of peptide chains and subsequent collapse of the resin is observed. Difficult sequences are sensed and appropriate action taken completely automatically.     

The effects of a 16-N-homopiperidino analogue of vecuronium on neuromuscular transmission in anaesthetized cats, pigs, dogs and monkeys, and in isolated preparations

Org 9991, a 16-N-homopiperidinium substituted vecuronium analogue, has been tested for neuromuscular blocking activity in anaesthetized cats, pigs, dogs and monkeys, and in isolated nerve-muscle preparations. Org 9991 exhibited non-depolarizing neuromuscular blocking activity of the competitive type, being reversible by neostigmine and showing no endplate channel blocking action in isolated preparations. In cats, 50% vagal block was observed at doses of Org 9991 approximately 10 times those producing 50% neuromuscular block; no ganglion block was seen at these doses. Effects on blood pressure or heart rate at 90% twitch blocking doses were either minor or absent. The potency and time course of action of Org 9991 remained similar in all four species: i.e. 90% block at ca 200-300 micrograms kg-1; onset time ca 1.2-1.9 min; duration 90% ca 4.5-8.9 min. This study suggests that 16-N-homopiperidinium analogues of vecuronium may provide leads in the quest for a potent non-depolarizing replacement for suxamethonium.     

Supplying emergency hormonal contraception in the pharmacy: the perspectives of service users

□ Pharmacists have been supplying emergency hormonal contraception via patient group direction in Manchester, Salford and Trafford health action zone since late 1999 □ This paper presents preliminary results of a questionnaire survey of users experiences of obtaining emergency contraception from this source □ Four hundred and thirty out of a total of 5,020 questionnaires distributed by pharmacists were completed □ Ninety‐nine per cent of service users were either very satisfied or satisfied with the manner in which their request for emergency contraception was dealt with □ Ninety‐one per cent of respondents felt either comfortable or very comfortable discussing emergency contraception with the pharmacist     

Teratology Study in Rats with Amsacrine, an Antineoplastic Agent

Teratology Study in Rats with Amsacrine, an Antineoplastic Agent.ANDERSON, J. A., PETRERE, J. A., SAKOWSKI, R., FITZGERALD, J.E., AND DE LA IGLESIA, F. A. (1986). Fundam. Appl. Toxicol.7, 214–220. Amsacrine, an acndinylamino derivative usedin the treatment of refractory leukemias, was evaluated forits teratogenic potential in pregnant rats. The compound wasgiven by intrapentoneal (ip) administration on Days 6 to 9 ofgestation to groups of 20 female CD rats at levels of 0.5, 1.0,and 2.0 mg/kg. Appropriate vehicle and untreated controls wereincluded. Dams given 2.0 mg/kg lost weight during and afterthe treatment period. Food consumption was comparable to controlsat all dose levels except for the high dose group in the post-treatmentperiod. Decreased litter size, increased postimplantation loss,and reduced fetal weights occurred with doses of 2.0 mg/kg.Significantly reduced fetal body weight and increased incidenceof stunting were the only adverse findings at 0.5 and 1.0 mg/kg,respectively. Two fetuses at 2.0 mg/kg, one at 1.0 mg/kg, oneat 0.5 mg/kg, and two vehicle control fetuses had gross abnormalities.Fetotoxicity, manifested by inhibition of osteogenesis and minorskeletal abnormalities, occurred with doses of 0.5 mg/kg ormore. The results indicate that amsacrine was embryolethal torats at doses of 2.0 mg/kg and embryotoxic at lower dose levels.Teratogenicity was not evident at doses which did not affectfetal survival.     

The role of Schwann cells and basal lamina tubes in the regeneration of axons through long lengths of freeze-killed nerve grafts

The ability of long acellular nerve grafts to support axonal regeneration was examined using inbred rats. Grafts (40 mm long) of tibial/plantar nerves were used either as live grafts or after freeze-drying to render the grafts acellular. The grafts were sutured to the proximal stump of severed tibial nerves in host animals which were then killed 1-12 weeks later. Axons rapidly regenerated through the living grafts but only extended 10-20 mm into the acellular grafts. This distance was achieved by 6 weeks and thereafter no significant further axonal extension occurred in the acellular grafts. A few naked axons lacking Schwann cell contact were identified in all acellular grafts, but became more numerous near the distal extent of axonal penetration into 6-12 week grafts. These axons contained large numbers of neurofilaments. When the distal 20 mm of 6 week acellular grafts (segments into which axons had not penetrated) were sutured to freshly severed tibial nerves, axons grew readily into the grafted tissue to a maximum distance of 9 mm. It is therefore likely that the limits to axonal regeneration through initially acellular grafts were set by factors intrinsic to the severed nerve. It is suggested that the limited migratory powers of Schwann cells may be one such factor. The concept that basal lamina tubes are not essential for axonal regeneration but may act as low resistance pathways for both axonal elongation and Schwann cell migration is discussed.     

Socio-economic achievements of individuals born very preterm at the age of 27 to 29 years: a nationwide cohort study

Aim  To describe the socio economic achievement of individuals born very preterm (VPT) at the age of 27 to 29 years.
Method  Demographic and social data were extracted from national registers for all individuals born between 1974 and 1976 in Denmark ( n =208 656). Of these, 203 283 individuals were alive in 2006. We compared VPT individuals (gestational age <33wks, n =1422; 51.8% males, n =736) with individuals born at term (>36wks, n =192 223; 51.1% males, n =98 240), of whom 4.08% ( n =58) of the VPT and 0.19% ( n =373) of the term individuals had a diagnosis of cerebral palsy (CP).
Results  Overall results in the two groups were similar, but significant differences appeared. The VPT group had a lower educational level than the term group: 23.9% versus 16.3% had a basic education (corresponding to attendance at basic school for 9y or less; odds ratio [OR] =1.61, 95% confidence interval [CI] 1.42–1.82). Similarly, 31.9% versus 37.6% had a tertiary education (corresponding to different levels of professional education; OR=0.77, CI 0.69–0.86). Net income was 11% lower in the VPT group and 10.8% versus 5.3% were receiving welfare support (OR=2.14, CI 1.81–2.55). In the VPT group 59% versus 52% did not have children ( p <0.001) and there were more individuals living alone without children (28.8% vs 21.8%; OR=1.45, CI 1.29–1.63).
Interpretation  VPT birth in the 1970s in Denmark is associated with a highly statistically significant educational and social disadvantage persisting into young adulthood. CP increased the relative risk of social disadvantage in VPT individuals. However, the majority of the survivors are well integrated in society.