Altered basal and insulin-stimulated phosphotyrosine phosphatase (PTPase) activity in skeletal muscle from NIDDM patients compared with control subjects

To measure possible changes in basal and insulin-stimulated phosphotyrosine phosphatase (PTPase) activity in skeletal muscle from insulin-resistant individuals, soluble and particulate muscle fractions were prepared from biopsies taken before and after a 3-h hyperinsulinaemic euglycaemic clamp in eight non-insulin-dependent diabetic (NIDDM) patients and nine control subjects. We used a sensitive sandwich-immunofluorescence assay and the human insulin receptor as the substrate. PTPase activity was expressed as percentage of dephosphorylation of phosphotyrosyl-residues in immobilized insulin receptors per 2 h incubation time per 83 micrograms and 19 micrograms muscle fraction protein (soluble and particulate fraction, respectively). In the diabetic soluble muscle fractions, the basal PTPase activity was decreased compared with that of control subjects (11.5 +/- 5.5 vs 27.5 +/- 3.3, p < 0.04, mean +/- SEM). In the particulate muscle fractions from the control subjects, PTPase activity was increased after 3 h hyperinsulinaemia (20.0 +/- 3.2 vs 30.2 +/- 3.6, p < 0.03) and in the corresponding soluble fractions PTPase activity seemed decreased (27.5 +/- 3.3 vs 19.9 +/- 5.9, NS). No effect of insulin on PTPase activity was found in NIDDM patients (25.1 +/- 4.1 vs 27.2 +/- 5.2, 11.5 +/- 5.5 vs 15.1 +/- 4.5 [particulate and soluble fractions], NS). In conclusion, we found that the basal PTPase activity in soluble muscle fractions was decreased in NIDDM patients; furthermore, insulin stimulation was unable to increase PTPase activities in the particulate fractions, as opposed to the effect of insulin in control subjects.     

Knowledge, attitude and behavior among patients with Chlamydia. Perspectives for prevention

Patients with chlamydial infections (Ct) attending the outpatient Venereal Disease Clinic of Copenhagen from July 1-November 30 1995 were asked to fill in a questionnaire focusing upon knowledge, attitude and behaviour related to sexually transmitted diseases (STDs) in order to strengthen the future prevention of Ct. The questionnaire was answered by 37 men and 35 women with a median age of 27 and 21 years and a median number of three and two sexual partners within the last six months, respectively. Half of the patients had previously had an STD, and 92% had been tested for HIV, of whom one homosexual man was known HIV-positive. Notification about exposure from a partner was the reason for attending for 24%. All but one were in favour of partner notification, but only 6% wanted provider referral. During last intercourse condoms had neither been used with a steady partner by 75% especially by the young and women, who thought themselves safe, nor with a casual partner by 52% especially among the young and men, mainly because of thoughtlessness or perception of low risk. Before the actual STD diagnosis only 49% were able to name one symptom and 35% one complication related to Ct. A majority (79%) stated, that fear of catching another Ct would lead to better protection, and 70% found that more information would have a preventive effect. Future Ct prevention programs in Denmark should include intensified chlamydial screening and partner notification together with centrally produced mass media information supplemented by individual counselling.     

Model based decision support for planning of road maintenance

In this article we describe a Decision Support Model, based on Operational Research methods, for the multi-period planning of maintenance of bituminous pavements. This model is a tool for the road manager to assist in generating an optimal maintenance plan for a road. Optimal means: minimising the Net Present Value of maintenance costs, while the plan is acceptable in terms of technical admissibility, resulting quality, etc. Global restrictions such as budget restrictions can also be imposed.Adequate grouping of maintenance activities in view of quantity discounts is an important aspect of our model. Our approach is to reduce the complexity of the optimisation by hierarchical structuring in four levels. In the lowest two levels maintenance per lane sector is considered, first with an unbounded planning horizon and next with a bounded planning horizon and time-windows for maintenance. The grouping of maintenance activities for a specific road is the topic of the third level. At the fourth level, which we will not consider in this article, the problem of optimal assignment of the available maintenance budgets over a set of roads or road sections takes place. Here, some results are presented to demonstrate the effects of grouping and to show that this hierarchical approach gives rise to improvements compared with previous work.     

Drug and narcotic use among Danish drivers

An investigation was made of the presence of drugs and narcotics in samples from Danish drivers having violated the Danish Road Traffic act in 1993. Four hundred and twenty-five cases were received, but only 317 cases were analysed for drugs or narcotics. In 256 cases drugs or narcotics were found present with a total of 531 findings. In 112 of the cases only one compound was found present. Benzodiazepines, morphine, methadone, cannabinoids and amphetamine were the most frequently occurring compounds with 239, 52, 42, 32 and 28 findings, respectively. The study has shown that especially the benzodiazepines together with the illicit drugs seem to constitute a threat to traffic safety. For two countries very much alike, namely Denmark and Norway this study has shown a remarkable difference in the number of samples analysed and the results found.     

Influence of the Multivalency of Ultrashort Arg‐Trp‐Based Antimicrobial Peptides (AMP) on Their Antibacterial Activity

Peptide dendrimers are a class of molecules of high interest in the search for new antibiotics. We used microwave‐assisted, copper(I)‐catalyzed alkyne–azide cycloaddition (CuAAC; “click” chemistry) for the simple and versatile synthesis of a new class of multivalent antimicrobial peptides (AMPs) containing solely arginine and tryptophan residues. To investigate the influence of multivalency on antibacterial activity, short solid‐phase‐ synthesized azide‐modified Arg‐Trp‐containing peptides were “clicked” to three different alkyne‐modified benzene scaffolds to access scaffolds with one, two, or three peptides. The antibacterial activity of 15 new AMPs was investigated by minimal inhibitory concentration (MIC) assays on five different bacterial strains, including a multidrug‐resistant Staphylococcus aureus (MRSA) strain. With ultrashort (2–3 residues) peptides, a clear synergistic effect of the trivalent display was observed, whereas this effect was not apparent with longer peptides. The best candidates showed activities in the low‐micromolar range against Gram‐positive MRSA. Surprisingly, the best activity against Gram‐negative Acinetobacter baumannii was observed with an ultrashort dipeptide on the trivalent scaffold (MIC: 7.5 μM ). The hemolytic activity was explored for the three most active peptides. At concentrations ten times the MIC values, <1 % hemolysis of red blood cells was observed.     

Contact tracing as a part of HIV infection prevention. Current practice and attitudes of general practitioners and hospital physicians; preliminary results

All doctors that had reported a newly-identified HIV infected person to the national HIV surveillance unit during a nine months period were traced and interviewed for one year later. The results of the interviews that related to 102 out of 195 (52%) reports were compared between the 48 interviewed general practitioners (GPs) and the 33 interviewed hospital doctors (HDs). Both GPs and HDs found it difficult to give a positive HIV test result and wanted to co-work with trained counsellors for the partner notification (PN) process. It was neither a routine for all GPs nor for all HDs to ask the patients about sexual behaviour and to discuss safe sex, and screening for other STD's was rarely performed. The number of partners notified was low. HIV reporting doctors in Denmark seem motivated for PN. The outcome of PN can only be measured to a certain level as long as exposed partners are neither obliged to be tested nor to be counselled and as long as information about counselling and testing can not be shared between doctors in different settings.     

On-chip self-calibrating communication techniques robust to electrical parameter variations

Dynamic self-calibration holds the promise of overcoming conservative worst-case design techniques needed to combat deep-submicron process and operating variations. We propose an on chip point-to-point interconnect scheme characterized by self-calibration that can operate dynamically to achieve the best energy/performance trade-off.     

Role of vitamin A elimination or supplementation diets during postnatal development on the allergic sensitisation in mice

Vitamin A (VA) and its derivatives, the retinoids, are important factors for the development of the immune system. It has been shown in adult animals that proliferation of lymphocyte populations and antibody secretion are retinoid dependent, while little is known about the effects of retinoids during postnatal development. The aim of this study was to investigate the role of VA on allergic sensitisation during lactation and after weaning using an in vivo system for postnatal allergic sensitisation in mice. Different VA diets (basal/VA elimination/VA (as retinyl palmitate) supplemented) were fed to the dams throughout lactation and directly to the pups after weaning. Allergic sensitisation was induced with a single peritoneal ovalbumin (OVA) injection at day 28 after weaning. The phenotype of lymphocytes was analysed by flow cytometry and functional data were obtained by analysis of (IL-4/IFN-gamma) cytokine production and antibody production (OVA-specific IgG1 and IgE) in the offspring. VA/retinyl palmitate supplementation during lactation and after weaning decreased CD3+, CD4+, CD8+ and B220+ populations in splenic lymphocytes but also significantly enhanced IL-4 production and OVA-specific IgE after sensitisation. In contrast, mice fed VA-elimination diet displayed no significant alteration of lymphocyte numbers and a slightly increased IL-4 production. Our results showed that a single allergen injection during postnatal development induces allergic sensitisation whose degree is modified by the VA content of the maternal diet during lactation and the diet of the pups after weaning, indicating an important role of VA on the severity of the allergic sensitisation.     

MGMT-Methylation in Non-Neoplastic Diseases of the Central Nervous System

Quantifying O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation plays an essential role in assessing the potential efficacy of alkylating agents in the chemotherapy of malignant gliomas. MGMT promoter methylation is considered to be a characteristic of subgroups of certain malignancies but has also been described in various peripheral inflammatory diseases. However, MGMT promoter methylation levels have not yet been investigated in non-neoplastic brain diseases. This study demonstrates for the first time that one can indeed detect slightly enhanced MGMT promoter methylation in individual cases of inflammatory demyelinating CNS diseases such as multiple sclerosis and progressive multifocal leucencephalopathy (PML), as well as in other demyelinating diseases such as central pontine and exptrapontine myelinolysis, and diseases with myelin damage such as Wallerian degeneration. In this context, we identified a reduction in the expression of the demethylase TET1 as a possible cause for the enhanced MGMT promoter methylation. Hence, we show for the first time that MGMT hypermethylation occurs in chronic diseases that are not strictly associated to distinct pathogens, oncogenic viruses or neoplasms but that lead to damage of the myelin sheath in various ways. While this gives new insights into epigenetic and pathophysiological processes involved in de- and remyelination, which might offer new therapeutic opportunities for demyelinating diseases in the future, it also reduces the specificity of MGMT hypermethylation as a tumor biomarker.