At the Centennial of Michaelis and Menten,Competing Michaelis–Menten Steps Explain Effect of GLP‐1 on Blood–Brain Transfer and Metabolism of Glucose

Glucagon‐like peptide‐1 (GLP‐1) is a potent insulinotropic incretin hormone with both pancreatic and extrapancreatic effects. Studies of GLP‐1 reveal significant effects in regions of brain tissue that regulate appetite and satiety. GLP‐1 mimetics are used for the treatment of type 2 diabetes mellitus. GLP‐1 interacts with peripheral functions in which the autonomic nervous system plays an important role, and emerging pre‐clinical findings indicate a potential neuroprotective role of the peptide, for example in models of stroke and in neurodegenerative disorders. A century ago, Leonor Michaelis and Maud Menten described the steady‐state enzyme kinetics that still apply to the multiple receptors, transporters and enzymes that define the biochemical reactions of the brain, including the glucose‐dependent impact of GLP‐1 on blood–brain glucose transfer and metabolism. This MiniReview examines the potential of GLP‐1 as a molecule of interest for the understanding of brain energy metabolism and with reference to the impact on brain metabolism related to appetite and satiety regulation, stroke and neurodegenerative disorders. These effects can be understood only by reference to the original formulation of the Michaelis–Menten equation as applied to a chain of kinetically controlled steps. Indeed, the effects of GLP‐1 receptor activation on blood–brain glucose transfer and brain metabolism of glucose depend on the glucose concentration and relative affinities of the steps both in vitro and in vivo, as in the pancreas.     

Does skin-to-skin contact reduce stress during diaper change in preterm infants?

Background

Skin-to-skin contact reduces pain response in preterm infants subjected to minor painful procedures, such as heel lance. Diaper change is a procedure performed several times daily in hospitalized preterm infants. Routine care giving tasks such as diaper change may be stressful for the infant.

Aims

The purpose of this study was to investigate whether diaper change induces stress and if skin-to-skin contact could reduce such stress, measured by changes in skin conductance.

Study design

This was a randomized crossover pilot study in 19 preterm infants with gestational age between 28 and 34 weeks. The diaper change procedure was done twice in each infant, once during skin-to-skin contact, and once in incubator or bed with the mother present.

Outcome measures

During diaper change heart rate (HR), peripheral oxygen saturation (SpO₂), and changes in skin conductance (SC) peaks per sec, using the Skin Conductance Algesimeter (SCA), were registered.

Results

The mean SC peaks/sec increased/decreased significantly under/after change of diapers which thereby underpins that this is a stressful procedure for the preterm infant.Skin-to-skin contact (SSC) entails significantly lower stress levels (p < 0.05) compared to diaper changed in an incubator/bed measured by the SCA.

Conclusions

Diaper change is a stressful procedure for preterm infants and may be ameliorated by skin-to-skin contact.     

A mutation update on the LDS‐associated genes TGFB2/3 and SMAD2/3

The Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor‐β (TGF‐β) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF‐β signaling. More recently, TGF‐β ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF‐β pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF‐β signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database.     

No influence of OPG and its ligands, RANKL and TRAIL, on proliferation and regulation of the calcification process in primary human vascular smooth muscle cells

The aim of this study was to examine the effects of the OPG-RANKL-TRAIL system on proliferation, regulation of calcification-associated genes and calcification of human vascular smooth muscle cells (HVSMCs). Small interfering (si)RNA-mediated knockdown of OPG was followed by treatment of HVSMCs with recombinant RANKL or TRAIL. Regulation of a calcification-associated gene set was assayed by pathway analysis of microarray results. The lack of OPG in HVSMCs or treatment with RANKL or TRAIL did not affect proliferation of HVSMCs. In addition, OPG, RANKL or TRAIL did not modify the regulation of a calcification-associated gene set. Finally, in the long term calcification assay, we found that cells isolated from seven different human donors showed a great variability in the response to RANKL and insulin. However, overall RANKL and/or insulin did not affect the development of calcification of HVSMCs. These studies indicate that OPG knockdown does not alter the calcification process in HVSMCs.     

Novel germline c-MET mutation in a family with hereditary papillary renal carcinoma

Hereditary papillary renal carcinoma (HPRC) is a highly penetrant hereditary renal cancer syndrome caused by germline missense mutations in the c-MET proto-oncogene. HPRC is clinically characterized by multiple bilateral papillary renal-cell carcinomas. Here we report a family with a novel missense mutation in c-MET. The original pathology report of four primary kidney cancers (1988–1997) revealed renal-cell carcinoma. A revised report described multiple adenomas and papillary renal-cell carcinomas with focal clear cells and a mixture of type 1 and type 2 pattern, emphasizing the importance of revised pathology examinations in possible hereditary renal-cell carcinomas especially when described before 1997.     

Associations between labial and whole salivary flow rates,systemic diseases and medications in a sample of older people

Smidt D, Torpet LA, Nauntofte B, Heegaard KM, Pedersen AML. Associations between labial and whole salivary flow rates, systemic diseases and medications in a sample of older people. Community Dent Oral Epidemiol 2010; 38: 422–435. © 2010 John Wiley & Sons A/S Abstract – Objective: To investigate the associations between age, gender, systemic diseases, medications and labial and whole salivary flow rates in older people. Methods: Unstimulated labial (LS) and unstimulated (UWS) and chewing‐stimulated (SWS) whole salivary flow rates were measured in 389 randomly selected community‐dwelling Danish women and 279 men aged 65–97 years. Systemic diseases, medications (coded according to the Anatomical Therapeutic Chemical (ATC) Classification System), tobacco and alcohol consumption were registered. Results: The number of diseases and medications was higher and UWS lower in the older age groups. On average, women were slightly older, had more diseases, higher medication intake and lower UWS, SWS and LS than men. High number of diseases and medications was associated with low UWS, SWS and LS. In the healthy (14%) and nonmedicated (19%) participants, flow rates were not associated with age and gender, apart from SWS being lower in nonmedicated women. Low UWS were associated with psychiatric and respiratory disorders, type 2 diabetes and intake of psycholeptics, psychoanaleptics (especially SRRIs), respiratory agents, oral antidiabetics (particularly sulfonylureas), magnesium‐hydroxide, cardiac agents, quinine, thiazides, calcium channel blockers, statins, urinary antispasmodics, glucosamine, NSAIDs, opioids and ophthalmologicals. SWS were lower in participants with ophthalmological disorders using ophthalmologicals (especially antiglaucoma agents and miotics), but also in those taking antidepressants, cardiac agents (mostly digitalis glycosides) and calcium channel blockers. Cardiovascular diseases and intake of anti‐thrombotics (mainly low dose aspirins), calcium channel blockers and oral antidiabetics were associated with low LS. Conclusions: In older people, low salivary flow rates are associated with specific and high number of diseases and medications, but neither with age and gender per se nor with tobacco and alcohol consumption. Low UWS are associated with more diseases and medications than SWS and LS, which were primarily associated with cardiovascular diseases and medications including preventive agents such as low‐dose aspirins and statins. New insights into medications and their association with salivary gland function were achieved using the ATC classification system.     

Can the patient perspective contribute to quality of nutritional care?

Scand J Caring Sci; 2011; 25; 176–184
Can the patient perspective contribute to quality of nutritional care? Aim: Undernutrition has been seen in hospitalized patients at all times. Nurses have a central position in the nutritional care of the patient. Despite guidelines for nutritional practise and care, 20–55% of patients are still at risk of complications to insufficient nutrition intake. The aim of this study was to obtain knowledge of hospitalized patient’s experiences of being undernourished, to understand implications this might have to quality of nutritional nursing care. Methods: Qualitative interviews were undertaken in 12 hospitalized patients at severe nutritional risk. Findings: Pain, no appetite, bad taste and side effects to medication were among reasons for poor eating. Nurses practically did not address or question symptoms that could influence poor eating and were only to a low degree involved at patient initiative. The patients appeared to divide into two groups; One ‘Passive group’, characterized with fatigue, lack of concentration and short term memory, were found insusceptible to increase nutrition intake by motivation and guidance. The overall motivation in the other ‘Active’ group was the setting of and achievement of goals, which had to be clear, communicated and followed up by nurses and physicians. This group furthermore found self‐determination and active involvement determinant for a positive and fruitful cooperation between staff and themselves. Conclusions: Nurses were in progressive about clarifying why patients did not eat. Patients highly regarded nutrition registration when followed up, however, this was only practised to a low degree. Severely undernourished patients could be divided in two groups. The ‘Passive group’ should be attended to systematically. Artificial nutrition is often needed in this group. The ‘Active group’ should be cared for with individual, active involvement from nurses. Nurses should be able to distinct which nutritional care for which patient, and act upon it.