Proteinases in renal cell death

The role of proteinases in renal proximal tubule (RPT) cellular death was examined using specific inhibitors of proteinases. Rabbit RPT suspensions were incubated with antimycin A for 1 h or tetrafluoroethyl-L-cysteine (TFEC) for 4 h in the absence or presence of the specific cysteine proteinase inhibitor L-trans-epoxysuccinyl-leucylamido (4-guanidino)butane (E-64), the serine proteinase inhibitors N-p-tosyl-L-lysine chloromethyl ketone (TLCK) or 3,4-dichloroisocoumarin (DCS), the serine and cysteine proteinase inhibitors leupeptin or antipain, or the aspartic proteinase inhibitor pepstatin. E-64 and pepstatin decreased lactate dehydrogenase (LDH) release, a marker of cell death, from RPT exposed either to antimycin A or TFEC. TLCK, DCS, leupeptin, or antipain did not decrease antimycin A- or TFEC-induced cell death. Bromohydroquinone- or t-butylhydroperoxide-induced cell death was not decreased by any of the proteinase inhibitors. Loss of lysosomal membrane potential, indicated by neutral red release, occurred prior to the onset of antimycin A-induced cell death. Extensive inhibition of lysosomal cathepsins B and L by E-64 was correlated with cytoprotection. However, E-64 was only protective after some cell death had occurred. These results suggest that lysosomal cysteine and aspartic proteinases, but not serine proteinases, play a role in RPT cell death induced by antimycin A or TFEC. The observation that E-64 was only protective after some cell death had occurred suggests that lysosomal cathepsins are released from dying cells and subsequently attack the remaining viable cells.     

Agreement between a frequency-weighted filter for continuous biomechanical measurements of repetitive wrist flexion against a load and published psychophysical data

A previous pilot study demonstrated that a force and frequency-weighted filter network could be developed for processing continuous biomechanical measures of repetitive wrist motions and exertions. The current study achieves the objective by modelling subjective discomfort for repetitive wrist flexion using controlled posture, pace and force. A three-level fractional factorial experiment was conducted involving repetitive wrist flexion (2 s/motion, 6 s/motion, 10 s/motion) from a neutral posture to a given angle (10 degrees, 28 degrees, 45 degrees) against a controlled resistance (5 N, 25 N, 50 N) using a Box Behnken design. Ten subjects participated. Discomfort was reported on a 10 cm visual analogue scale. Results of response surface regression analysis revealed that main effects of force, wrist flexion angle, and repetition were all significant (p < 0.05) and that no second-order effects were observed. Linear regression analysis on these factors established a discomfort model on which the filter characteristics were based. The pure error test model revealed no significant lack of fit (p > 0.05). The continuous model was compared and agreed with discrete psychophysical data from other published studies. The model was used for generating parameters for a force and frequency-weighted digital filter that weighs continuous wrist postural signals with corresponding force in proportion to the equal discomfort function as a function of frequency of repetition. These filters will enable integration of large quantities of biomechanical data in field studies.     

Effect of pentobarbital on normal brain protection and on the response of 9L rat brain tumor to radiation therapy

The authors attempted to confirm published reports that pentobarbital protects against radiation-induced damage to normal rat brain, as well as enhances radiotherapeutic efficacy in a rat brain tumor model. They evaluated animal survival in 9L gliosarcoma-burdened rats that received whole-brain radiation therapy (16, 24, 32, or 40 Gy) while under intraperitoneal pentobarbital (60 mg/kg) or intramuscular ketamine (60 mg/kg) sedation. The animals were examined at autopsy to attribute death to either intracranial tumor growth or normal brain toxicity in the absence of discernible tumor. There was no difference between the two anesthesia groups regarding the survival of unirradiated animals. Radiation therapy produced a significant dose-dependent prolongation in animal survival, which was limited by the development of normal tissue toxicity at the higher doses. When compared to ketamine anesthesia, pentobarbital anesthesia appeared to offer some protection (not statistically significant) against early (but not late) toxicity at selected radiation doses. A reduction in the number of deaths from tissue toxicity suggested an increased antitumor effect, but again this was not statistically significant. Only in one case was there even a marginal significant difference (p = 0.045) between overall therapeutic efficacy in rats sedated with pentobarbital versus ketamine. While there may be a radioprotective effect of pentobarbital in rat brains without intracranial tumor, there is no conclusive evidence for either radioprotection or significant improvement of radiotherapeutic efficacy in this 9L rat brain tumor model.     

Cisapride reduces neonatal postoperative ileus: randomised placebo controlled trial

AIM: To assess the efficacy of cisapride in reducing ileus persisting to the tenth postoperative day after neonatal abdominal surgery. METHODS: A prospective, randomised, double blind trial comparing rectal cisapride (1.4-2.3 mg/kg/day) with placebo over seven days was undertaken in 33 neonates. RESULTS: Seven of 12 (58%) patients receiving placebo and eight of 11 (73%) receiving cisapride achieved a first sustained feed during treatment. Of those receiving cisapride, the first sustained feed occurred at 2.3 days (SEM 0.6) compared with 4.7 days (SEM 0.8) with placebo. By the seventh day the mean daily net enteral balance was 69 (SEM 18) ml/kg in the cisapride subgroup and 17 (SEM 8) ml/kg for those receiving placebo. Stool was passed on 6.3 (SEM 0.4) treatment days in the cisapride subgroup compared with 4.1 (SEM 1.0) treatment days in the placebo subgroup. CONCLUSION: Cisapride is effective in neonates with a prolonged ileus after abdominal surgery.     

Warfarin anticoagulation in primary care: a regional survey of present practice and clinicians' views

The demand for anticoagulation services is rising. Warfarin anticoagulation has been shown to reduce the risk of stroke in patients with non-valvular atrial fibrillation by 68%. This raises issues about how services are best organized to initiate and monitor anticoagulation in this potentially large group of patients. We report the results of a regional postal survey undertaken to describe the views of general practitioners and consultants regarding warfarin anticoagulation in light of this potentially high increase in demand.     

Changes in identity and self-organization in psychotherapy of multiple personality disorder.

Studied change in client identity and self-organization during the treatment of a 38-yr-old man with multiple personality disorder. Assessment measures were administered to the host personality and 2 secondary personalities before and after 12 wks of intensive treatment. Measures included the MMPI and the Bell Object Relations Reality Testing Inventory (BORRTI). Therapy focused on the posttraumatic aspects of the patient's early childhood sexual abuse. A cognitive-affective approach combined psychoanalytically informed psychotherapy with abreactive-hypnotic work for recovering and reexamining traumatic memories. A greater degree of intrapsychic awareness and interpersonal sensitivity was suggested by changes in BORRTI ratings. The magnitude of observed changes in self-organization was substantial. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experience with Applying Formal Methods to Protocol Specification and System Architecture

In the last three years or so we at Enterprise Platforms Group at Intel Corporation have been applying formal methods to various problems that arose during the process of defining platform architectures for Intel's processor families. In this paper we give an overview of some of the problems we have worked on, the results we have obtained, and the lessons we have learned. The last topic is addressed mainly from the perspective of platform architects.     

Nephelometric study of salivary protein–tannin aggregates

Grape seed procyanidins were fractionated through different degrees of polymerisation, and human saliva was purified and separated into two fractions: one was mostly α‐amylase and the other was essentially proline‐rich proteins (PRPs). The interaction of these proteins with the procyanidin compounds was assayed using nephelometry, and the influence of several factors was investigated, such as degree of polymerisation, pH and concentrations of both protein and tannin. The same experiments were performed with bovine serum albumin (BSA). The amount of insoluble aggregates, resulting from the formation of polyphenol–protein aggregates, increased quickly up to a maximum value which thereafter remained practically unchanged. pH was set at 5.0 for all further assays, since it was the nearest value to that encountered in human saliva (pH 5.6–7.9), where proteins were stable and had a maximum ability to bind and precipitate procyanidin oligomers. These proteins were shown to have a strong affinity for procyanidin oligomers and were unable to resolubilise the polyphenol–protein aggregates when present in excess. PRPs required a much lower content to bind all the tannins (400 µg of procyanidin oligomers) than BSA and especially α‐amylase (48, 60 and 132 µg respectively). The procyanidin's ability to bind PRPs, BSA and α‐amylase increased with its average molecular weight. This ability increased regularly for PRPs up to 4500 Da, whereas the ability to bind the globular proteins decreased beyond 3400 Da. © 2001 Society of Chemical Industry