Changes to insulin sensitivity in glucose clearance systems and redox following dietary supplementation with a novel cysteine-rich protein: A pilot randomized controlled trial in humans with type-2 diabetes.

We recently developed a novel keratin-derived protein (KDP) rich in cysteine, glycine, and arginine, with the potential to alter tissue redox status and insulin sensitivity. The KDP was tested in 35 human adults with type-2 diabetes mellitus (T2DM) in a 14-wk randomised controlled pilot trial comprising three 2×20 g supplemental protein/day arms: KDP-whey (KDPWHE), whey (WHEY), non-protein isocaloric control (CON), with standardised exercise. Outcomes were measured morning fasted and following insulin-stimulation (80 mU/m2/min hyperinsulinaemic-isoglycaemic clamp). With KDPWHE supplementation there was good and very-good evidence for moderate-sized increases in insulin-stimulated glucose clearance rate (GCR; 26%; 90% confidence limits, CL 2%, 49%) and skeletal-muscle microvascular blood flow (46%; 16%, 83%), respectively, and good evidence for increased insulin-stimulated sarcoplasmic GLUT4 translocation (18%; 0%, 39%) vs CON. In contrast, WHEY did not effect GCR (-2%; -25%, 21%) and attenuated HbA1c lowering (14%; 5%, 24%) vs CON. KDPWHE effects on basal glutathione in erythrocytes and skeletal muscle were unclear, but in muscle there was very-good evidence for large increases in oxidised peroxiredoxin isoform 2 (oxiPRX2) (19%; 2.2%, 35%) and good evidence for lower GPx1 concentrations (-40%; -4.3%, -63%) vs CON; insulin stimulation, however, attenuated the basal oxiPRX2 response (4%; -16%, 24%), and increased GPx1 (39%; -5%, 101%) and SOD1 (26%; -3%, 60%) protein expression. Effects of KDPWHE on oxiPRX3 and NRF2 content, phosphorylation of capillary eNOS and insulin-signalling proteins upstream of GLUT4 translocation AktSer437 and AS160Thr642 were inconclusive, but there was good evidence for increased IRSSer312 (41%; 3%, 95%), insulin-stimulated NFκB-DNA binding (46%; 3.4%, 105%), and basal PAK-1Thr423/2Thr402 phosphorylation (143%; 66%, 257%) vs WHEY. Our findings provide good evidence to suggest that dietary supplementation with a novel edible keratin protein in humans with T2DM may increase glucose clearance and modify skeletal-muscle tissue redox and insulin sensitivity within systems involving peroxiredoxins, antioxidant expression, and glucose uptake.

Cervical spine meniscoids: an update on their morphological characteristics and potential clinical significance.

PURPOSE: Cervical spine meniscoids are intra-articular folds of synovial membrane that have been theorised to have potential clinical significance in neck pain. Recent anatomical and clinical research has re-visited the pathoanatomical capacity of these structures. The purpose of this review is to discuss cervical spine meniscoid morphology in light of recently published work, to provide an update on the plausible relevance of these structures to clinical practice. METHODS: Narrative review critically discussing basic science and clinical research regarding cervical spine meniscoids, with focus upon implications for clinical practice. RESULTS: Basic science research indicates that cervical spine meniscoids can be innervated and appear to vary in morphology in the presence of articular degeneration. In a clinical population, associations have been observed between cervical spine meniscoid morphology and presence of cervical spine symptoms. CONCLUSIONS: Recent studies regarding cervical spine meniscoid morphology provide further evidence of pathoanatomical capacity of these structures. Further research is required, however, in clinical populations to empirically investigate specific theorised mechanisms of cervical spine meniscoid involvement in neck pain.

Multivariate assessment of site of lingual nerve.

Injury to the lingual nerve can cause debilitating symptoms. The nerve lies in the retromolar region and its anatomical site can vary within patients and according to sex, age, and dentate status. To our knowledge, no previous studies have recorded its course from multiple bony landmarks and examined the association between age, dentate status, and sex, in the same sample. We dissected 30 white cadavers and took primary and secondary reference points from the internal oblique ridge. We measured the distance to the lingual nerve in sagittal, vertical, and horizontal planes, and recorded the position where the nerve was closest to the lingual plate. We dissected 46 hemimandibles (23 male, mean age 79 years, range 52-100) of which 26 were from the left side. Mean (SD) sagittal, vertical, and horizontal distances from the primary reference point were 9.29 (3.41)mm, 9.15 (3.87)mm, and 0.57 (0.56)mm, respectively. Mean (SD) vertical and horizontal distances from the secondary point were 7.79 (5.45) mm and 0.59 (0.64)mm, respectively. The proximity of the nerve to the lingual plate varied widely (range -13.00 to 15.17mm from the primary reference point). Dentate status was significant for the sagittal measurement from the primary point, and the vertical measurement from the secondary point. Differences in age, sex, or site of the contralateral nerve were not significant (n=16 pairs). Our findings suggest that the site of the nerve is consistent between and within subjects for sex and age, but not for dentate status. The association between the nerve and the lingual plate varied, which suggests that care must be taken when operating in the area.

Are nursing students safe when choosing gluteal intramuscular injection locations?

BACKGROUND: Nurses are required to perform gluteal intramuscular (IM) injections in practice. There are dangers associated with erroneous performance of this task, particularly with dorsogluteal injections. Knowledge regarding safe injection practice is therefore vital for nursing students. METHOD: Fifty-eight second year students at a New Zealand Nursing School were given schematic drawings of the posterior and lateral aspects of the gluteal region. They were asked to mark and justify the safest location for gluteal IM injections. RESULTS: Fifty-seven students marked the dorsal schematic and one the lateral, with 38 (66.7%) marking in the upper outer quadrant (UOQ). Twenty indicating the UOQ (52.6%) wrote 'sciatic' or 'nerve' in justifying their location. Nineteen (33.3%) marked a location outside the UOQ; nine (47.4%) of these mentioned 'sciatic' or 'nerve' as reasons for injection safety. Overall, 50% of students mentioned 'sciatic' or 'nerve' in justifying the safety of their chosen injection location. CONCLUSION: Results suggest some second year nursing students do not understand safe gluteal IM injection locations and rationale. Current teaching practices and IM injection techniques could be revisited to prepare students more effectively; this may help prevent pathologies arising from this procedure.

The effects of World Health Organization chemotherapy on imported leprosy in Auckland, New Zealand, 1983-90.

Between January 1983 and December 1990 in Auckland, New Zealand, 87 patients (28 paucibacillary disease (PBD) and 59 multibacillary disease (MBD)) commenced WHO multidrug therapy (MDT). All were immigrants from the Pacific Islands (65) or Asia (22). A total of 57 patients had already received non-WHO regimens, some continuously, but often intermittently, for many years; 30 patients received WHO MDT only. By December 1990, 50 had completed treatment, with 1 relapse and 1 late reaction, both in patients with PBD treated with WHO MDT only. There have been no relapses in those treated with WHO MDT after prior leprosy treatment. In those with MBD, type II leprosy reactions were less common (16%) in those treated only with WHO MDT than in those treated continuously before 1983 with older regimens (64%). Type I leprosy reactions occurred in about 20% of both these groups. The bacterial index fell faster in those who had had a prolonged prior treatment beginning WHO MDT than in those starting WHO MDT as their initial leprosy chemotherapy. Overall we found WHO MDT was well accepted and the compliance good, but 13 patients (15%) left Auckland before treatment was completed and 6 (7%) during follow up.

Collateral axons of cholinergic pontine neurones projecting to midline, mediodorsal and parafascicular thalamic nuclei in the rat.

The organization of collateral axons projecting from neurones in the pontine laterodorsal tegmental nucleus (LDTg) has been examined using combinations of retrograde neuronal tracers with immunocytochemical markers for the acetylcholine-synthesizing enzyme choline acetyltransferase (CHAT), focussing on projections to the midline, mediodorsal and parafascicular thalamic nuclei and the ventral tegmental area. 25-59% of LDTg neurones projecting to the mediodorsal nucleus provided collaterals to the midline nuclei. Virtually all (87-96%) of these double retrogradely labelled neurones appeared cholinergic. 9-18% of LDTg neurones projecting to the parafascicular nuclei also provided a collateral to the midline nuclei and 50-78% of these double retrogradely labelled neurones stained for CHAT. 26-29% of the single LDTg neurones which projected collaterals to both the mediodorsal and midline nuclei, were found to project a third collateral to the ventral tegmental area. These anatomical findings, taken together with functional evidence, suggest that cholinergic terminals arising from LDTg are involved in coordinating thalamic mechanisms of brain state control; and in regulating dopaminergic pathways, both directly and via the thalamus.

Afferent and efferent connections of the laterodorsal tegmental nucleus in the rat.

The connections of the laterodorsal tegmental nucleus (LDTg) have been investigated using anterograde and retrograde lectin tracers with immunocytochemical detection. Inputs to LDTg were found from frontal cortex, diagonal band, preoptic areas, lateral hypothalamus, lateral mamillary nucleus, lateral habenula; the interpeduncular nucleus, ventral tegmental area, substantia nigra and retrorubral fields; the medial terminal nucleus, interstitial nucleus, supraoculomotor central grey, medial pretectum, nucleus of the posterior commissure, paramedian pontine reticular formation, paraabducens and paratrochlear region; the parabrachial nuclei and nucleus of the tractus solitarius. Terminal labelling from PHA-L injections of LDTg was found in infralimbic, cingulate and hippocampal cortex, lateral septum, septofimbrial and triangular nuclei, horizontal limb of diagonal band and preoptic areas; in the anterior, mediodorsal, reuniens, centrolateral, parafascicular, paraventricular and laterodorsal thalamic nuclei, rostral reticular thalamic nucleus, and zona incerta; the lateral habenula and the lateral hypothalamus. A number of brainstem structures apparently associated with visual functions were also innervated, mainly the superior colliculus, medial pretectum, medial terminal nucleus, paramedian pontine reticular formation, inferior olive, supraoculomotor, paraabducens and supragenual regions, prepositus hypoglossi and nucleus of the posterior commissure. Also innervated were substantia nigra compacta, ventral tegmental area, interfascicular nucleus, interpeduncular nucleus, dorsal and medial raphe, pedunculopontine tegmental region, parabrachial nuclei, and nucleus of the tractus solitarius. These findings suggest the LDTg to be a highly differentiated part of the ascending "reticular activating" system, concerned not only with specific cortical and thalamic regions, especially those associated with the limbic system, but also with the basal ganglia, and visual (particularly oculomotor) mechanisms. Additional links with the habenula-interpeduncular system are discussed in this context.

Projections to the rostral reticular thalamic nucleus in the rat.

Afferent pathways to the rostral reticular thalamic nucleus (Rt) in the rat were studied using anterograde and retrograde lectin tracing techniques, with sensitive immunocytochemical methods. The analysis was carried out to further investigate previously described subregions of the reticular thalamic nucleus, which are related to subdivisions of the dorsal thalamus, in the paraventricular and midline nuclei and three segments of the mediodorsal thalamic nucleus. Cortical inputs to the rostral reticular nucleus were found from lamina VI of cingulate, orbital and infralimbic cortex. These projected with a clear topography to lateral, intermediate and medial reticular nucleus respectively. Thalamic inputs were found from lateral and central segments of the mediodorsal nucleus to the lateral and intermediate rostral reticular nucleus respectively and heavy paraventricular thalamic inputs were found to the medial reticular nucleus. In the basal forebrain, afferents were found from the vertical and horizontal limbs of the diagonal band, substantia innominata, ventral pallidum and medial globus pallidus. Brainstem projections were identified from ventrolateral periaqueductal grey and adjacent sites in the mesencephalic reticular formation, laterodorsal tegmental nucleus, pedunculopontine nucleus, medial pretectum and ventral tegmental area. The results suggest a general similarity in the organisation of some brainstem Rt afferents in rat and cat, but also show previously unsuspected inputs. Furthermore, there appear to be at least two functional subdivisions of rostral Rt which is reflected by their connections with cortex and thalamus. The studies also extend recent findings that the ventral striatum, via inputs from the paraventricular thalamic nucleus, is included in the circuitry of the rostral Rt, providing further evidence that basal ganglia may function in concert with Rt. Evidence is also outlined with regard to the possibility that rostral Rt plays a significant role in visuomotor functions.

Single neurones of the basal forebrain and laterodorsal tegmental nucleus project by collateral axons to the olfactory bulb and the mediodorsal nucleus in the rat.

The branching pattern of axons arising from cells in the basal forebrain and laterodorsal tegmental nucleus of the pontine grey, was examined using the double retrograde transport of rhodamine- and coumarin-labelled latex microspheres injected into the olfactory bulb and the mediodorsal thalamic nucleus. About 30-50% of basal forebrain neurones were double-labelled, and approximately 30-40% of laterodorsal tegmental neurones were double-labelled ipsilateral to the injections. No contralateral single or double label was observed in the basal forebrain, but approximately 30% of the contralateral laterodorsal tegmental projection was also double-labelled.