Contraction of the abdominal muscles associated with movement of the lower limb

Background and Purpose. Activity of the trunk muscles is essential for maintaining stability of the lumbar spine because of the unstable structure of that portion of the spine. A model involving evaluation of the response of the lumbar multifidus and abdominal muscles to leg movement was developed to evaluate this function. Subjects. To examine this function in healthy persons, 9 male and 6 female subjects (mean age = 20.6 years, SD = 2.3) with no history of low back pain were studied. Methods. Fine-wire and surface electromyography electrodes were used to record the activity of selected trunk muscles and the prime movers for hip flexion, abduction, and extension during hip movements in each of these directions. Results. Trunk muscle activity occurring prior to activity of the prime mover of the limb was associated with hip movement in each direction. The transversus abdominis (TrA) muscle was invariably the first muscle that was active. Although reaction time for the TrA and oblique abdominal muscles was consistent across movement directions, reaction time for the rectus abdominis and multifidus muscles varied with the direction of limb movement. Conclusion and Discussion. Results suggest that the central nervous st stem deals with stabilization of the spine by contraction of the abdominal and multifidus muscles in anticipation of reactive forces produced by limb movement. The TrA and oblique abdominal muscles appear to contribute to a function not related to the direction of these forces.

Tenoxicam controls pain without altering orthodontic movement of maxillary canines

Arantes GM, Arantes VMN, Ashmawi HA, Posso IP To study the efficacy of tenoxicam for pain control, its potential for preemptive analgesia, and its influence on the orthodontic movement of upper canine teeth. This was a randomized controlled double-blind cross-over study. The patients were divided into three groups. Two groups received tenoxicam in daily doses of 20 mg orally for 3 days. Group A received the first dose of the drug before orthodontic activation and group B, just afterwards. Group C (control) received a placebo for 3 days. All groups had access to 750 mg of paracetamol up to four times a day. Three orthodontic activations were performed at 30-day intervals. Each patient belonged to two different groups. Pain intensity was assessed using a descriptive Pain Scale and a Visual Analog Scale. Private clinic; 36 patients undergoing bilateral canine tooth retraction. The statistical analysis did not show any difference in movement between the active groups and the control at any time. There was no statistical difference between the groups that received tenoxicam. Pain intensity in these groups was lower than in the placebo group. The difference in pain intensity between the active groups and the control was greatest at the assessment made 12 h after activation and it tended to zero, 72 h after activation. Tenoxicam did not influence orthodontic movement of the upper canines. It was effective for pain control and did not present any preemptive analgesic effect.

Gold(III) template synthesis of a pendant-arm macrocycle

Gold(III)-directed condensation of ethane-1,2-diamine with nitroethane and formaldehyde yielded the gold-coloured macrocyclic complex (cis-6,13-dimethyl-6,13-dinitro-1,4,8,11-tetraazacyclotetradecan-1-ido)gold(III) and the orange acyclic complex (1,9-diamino-5-methyl-5-nitro-3,7-diazanoran-3-ido)gold(III) in good yields. Dissolution in strongly acidic solution gave the colourless fully protonated complexes. The pendant nitro groups are disposed on the same side of the macrocycle in a cis geometry, as confirmed by crystal structure analysis. In both complexes the gold ion lies in a square-planar environment of four nitrogen donors, and the co-ordinate bond to the deprotonated amine is shorter than the remaining Au-N distances.

The p.A2215D Thyroglobulin Gene Mutation Leads to Deficient Synthesis and Secretion of the Mutated Protein and Congenital Hypothyroidism with Wide Phenotype Variation

Context: Thyroglobulin (TG) is a large glycoprotein and functions as a matrix for thyroid hormone synthesis. TG gene mutations give rise to goitrous congenital hypothyroidism (CH) with considerable phenotype variation. Objectives: The aim of the study was to report the genetic screening of 15 patients with CH due to TG gene mutations and to perform functional analysis of the p. A2215D mutation. Design: Clinical evaluation and DNA sequencing of the TG gene were performed in all patients. TG expression was analyzed in the goitrous tissue of one patient. Human cells were transfected with expression vectors containing mutated and wild-type human TG cDNA. Results: All patients had an absent rise of serum TG after stimulation with recombinant human TSH. Sequence analysis revealed three previously described mutations (p. A2215D, p. R277X, and g. IVS30 + 1G > T), and two novel mutations (p. Q2142X and g. IVS46-1G > A). Two known (g. IVS30 + 1G/p. A2215D and p. A2215D/p. R277X) and one novel (p. R277X/g. IVS46-1G > A) compound heterozygous constellations were also identified. Functional analysis indicated deficiency in TG synthesis, reduction of TG secretion, and retention of the mutant TG within the cell, leading to an endoplasmic reticulum storage disease, whereas small amounts of mutant TG were still secreted within the cell system. Conclusion: All studied patients were either homozygous or heterozygous for TG gene mutations. Two novel mutations have been detected, and we show that TG mutation p. A2215D promotes the retention of TG within the endoplasmic reticulum and reduces TG synthesis and secretion, causing mild hypothyroidism. In the presence of sufficient iodine supply, some patients with TG mutations are able to compensate the impaired hormonogenesis and generate thyroid hormone. (J Clin Endocrinol Metab 94: 2938-2944, 2009)

HDL-C concentration is related to markers of absorption and of cholesterol synthesis: Study in subjects with low vs. high HDL-C

Background: The antiatherogenic functions of high density lipoprotein (HDL-C) include its role in reverse cholesterol transport, but to what extent the concentration of HDL-C interferes with the whole-body cholesterol metabolism is unknown. Therefore, we measured markers of body cholesterol synthesis (desmosterol and lathosterol) and of intestinal cholesterol absorption (campesterol and beta-sitosterol) in healthy subjects that differ according to their plasma HDL-C concentrations. Methods: Healthy participants presented either low HDL-C (<40 mg/dl, n = 33,17 male and 16 female) or high HDL-C (>60 mg/dl, n = 33, 17 male and 16 female), BMI <30 kg/m(2), were paired according to age and gender, without secondary factors that might interfere with their plasma lipid concentrations. Plasma concentrations of non-cholesterol sterols were measured by the combined GC-MS analysis. Results: Plasma desmosterol did not differ between the two groups; however, as compared with the high HDL-C participants, the low HDL-C participants presented higher concentration of lathosterol and lower concentration of the intestinal cholesterol absorption markers campesterol and beta-sitosterol. Conclusion: Plasma concentrations of HDL, and not the activities of LCAT and CETP that regulate the reverse cholesterol transport system, correlate with plasma sterol markers of intestinal cholesterol absorption directly, and of cholesterol synthesis reciprocally. (C) 2010 Elsevier B.V. All rights reserved.

A synthesis of the findings from the Quake Impact Study: A two year investigation of the psychosocial sequelae of the 1989 Newcastle earthquake

This paper summarises the major findings from the Quake Impact Study (QIS), a four-phase longitudinal project that was conducted in the aftermath of the 1989 Newcastle (Australia) earthquake. A total of 3,484 subjects participated in at least one component of the QIS, comprising a stratified sample of 3,007 drawn from community electoral rolls and 477 from specially targeted supplementary samples (the injured, the displaced, the owners of damaged businesses, and the helpers). Subjects' initial earthquake experiences were rated in terms of weighted indices of exposure to threat and disruption. Psychological morbidity was measured at each phase using the General Health Questionnaire (GHQ-12) and the Impact of Event Scale (IES). Selected findings and key conclusions are presented for each of six areas of investigation: service utilisation during the first 6 months post-disaster; patterns of earthquake experience and short-term (6-month) psychosocial outcome; earthquake exposure and medium term (2-year) psychosocial outcome; vulnerability factors and medium-term psychosocial outcome: specific community groups at increased risk (e.g., the elderly and immigrants from non-English-speaking backgrounds); the effects of stress debriefing for helpers. Threshold morbidity (i.e., likely caseness) rates are also presented for a broad range of subgroups. In addition to presenting an overview of the QIS, this paper synthesises the major findings and discusses their implications for future disaster management and research from a mental health perspective.

Synthesis of alpha-aspartyl-containing cyclic peptides

alpha-Aspartyl-containing cyclic pentapeptides were synthesised in high yields using a strategy that maintained fluorenylmethyl protection on the aspartic acid side chain during chain assembly, resin cleavage and cyclisation of the linear precursors. Tetra-n-butylammonium fluoride treatment of the fluorenylmethyl-protected cyclic peptides catalysed imide formation, whereas piperidine-induced deprotection resulted in good yields of the target cyclic peptides.

LOSS OF CD40 ENDOGENOUS S-NITROSYLATION DURING INFLAMMATORY RESPONSE IN ENDOTOXEMIC MICE AND PATIENTS WITH SEPSIS

Signal transduction through the surface molecule CD40 is critical for cellular activation in immunoinflammatory states such as sepsis. The mechanisms regulating this pathway are not completely understood. Because CD40 displays potentially regulatory cysteine residues and CD40 is probably exposed to NO in the inflammatory milieu, we hypothesized that S-nitrosylation, the interaction of NO with cysteines residues, acts as a post-translational modification on CD40, coregulating the signaling activity and, therefore, the level of cellular activation. As assessed by the biotin switch and the reduction/chemiluminescence S-nitrosylation detection techniques, CD40 was found to be S-nitrosylated endogenously and upon exposure to NO donors in both human and murine macrophages. S-nitrosylation of CD40 was associated with milder activation by its ligand (CD40L), leading to reduced in vitro cytokine (IL-1 beta, IL-12, and TNF-alpha) production, which was reversed in the presence of inhibitors of NO synthesis. S-nitrosylated CD40 was found in resting RAW 246.7 macrophages and BALB/c mice peritoneal macrophages, turning into the denitrosylated state upon in vitro or systemic exposure, respectively, to LPS. Moreover, monocytes from patients with sepsis displayed denitrosylated CD40 in contrast to the CD40 S-nitrosylation measured in healthy individuals. Finally, in an attempt to explain how S-nitrosylation regulates CD40 activation, we demonstrate that NO affects the redistribution of CD40 on the cell surface, which is a requirement for optimal signal transduction. Our results support a novel post-translational regulatory mechanism in which the CD40 signal may be, at least in part, dependent on cellular activation-induced receptor denitrosylation.

An investigation into the synthesis of polycarbazole squaraine derivatives

The polycondensation of squaric acid with 1,2-(9-Ethylcarbazol-3-yl)ethene and N-ethyliminostilbene in polyphosphoric acid yielded insoluble polymers which included substituted phosphate groups on the phenyl rings. The presence of phosphorus in these polymers was identified using solid-state P-31 NMR and EDAX techniques. Furthermore the phosphate groups were not ionic, hence no charge-balancing anions were present; Both polymers did not electrically conduct but exhibited dielectric breakdown values of 0.1 and 0.06 MV cm(-1) respectively.

Feedforward contraction of transversus abdominis is not influenced by the direction of arm movement

Because the structure of the spine is inherently unstable, muscle activation is essential for the maintenance of trunk posture and intervertebral control when the limbs are moved. To investigate how the central nervous system deals with this situation the temporal components of the response of the muscles of the trunk were evaluated during rapid limb movement performed in response to a visual stimulus. Fine-wire electromyography (EMG) electrodes were inserted into transversus abdominis (TrA), obliquus internus abdominis (OI) and obliquus externus abdominis (OE) of 15 subjects under the guidance of real-time ultrasound imaging. Surface electrodes were placed over rectus abdominis (RA), lumbar multifidus (MF) and the three parts of deltoid. In a standing position, ten repetitions of shoulder flexion, abduction and extension were performed by the subjects as fast as possible in response to a visual stimulus. The onset of TrA EMG occurred in advance of deltoid irrespective of the movement direction. The time to onset of EMC activity of OI, OE, RA and MF varied with the movement direction, being activated earliest when the prime action of the muscle opposed the reactive forces associated with the specific limb movement. It is postulated that the non-direction-specific contraction of TrA may be related to the control of trunk. stability independent of the requirement for direction-specific control of the centre of gravity in relation to the base of support.

Impairments of movement kinematics in patients with Huntington's disease: A comparison with and without a concurrent task

This study aimed to quantify the efficiency and smoothness of voluntary movement in Huntington's disease (HD) by the use of a graphics tablet that permits analysis of movement profiles. In particular, we aimed to ascertain whether a concurrent task (digit span) would affect the kinematics of goal-directed movements. Twelve patients with HD and their matched controls performed 12 vertical zig-zag movements, with both left and right hands (with and without the concurrent task), to large or small circular targets over long or short extents. The concurrent task was associated with shorter movement times and reduced right-hand superiority. Patients with HD were overall slower, especially with long strokes, and had similar peak velocities for both small and large targets, so that controls could better accommodate differences in target size. Patients with HD spent more time decelerating, especially with small targets, whereas controls allocated more nearly equal proportions of time to the acceleration and deceleration phases of movement, especially with large targets. Short strokes were generally less force inefficient than were long strokes, especially so for either hand in either group in the absence of the concurrent task, and for the right hand in its presence. With the concurrent task, however, the left hand's behavior changed differentially for the two groups; for patients with HD, it became more force efficient with short strokes and even less efficient with long strokes, whereas for controls, it became more efficient with long strokes. Controls may be able to divert attention away from the inferior left hand, increasing its automaticity, whereas patients with HD, because of disease, may be forced to engage even further online visual control under the demands of a concurrent task. Patients with HD may perhaps become increasingly reliant on terminal visual guidance, which indicates an impairment in constructing and refining an internal representation of the movement necessary for its. effective execution. Basal ganglia dysfunction may impair the ability to use internally generated cues to guide movement.

Synthesis of fructans by partially purified fructosyltransferase activities from Lolium rigidum

Sucrose:sucrose fructosyltransferase (SST) activity was partially purified from whole shoots of Lolium rigidum by a combination of affinity chromatography, gel filtration and anion-exchange chromatography. The SST activity co-eluted with some fructan:fructan fructosyltransferase (FFT) and invertase activities and consequently the partially purified preparation was termed the fructosyltransferase (FT) preparation. The SST-like activity in the FT preparation was purified 214-fold and had an apparent molecular mass of 84 000. The FT preparation contained several peptides with an apparent pI of 4.6-4.7. When assayed with sucrose concentrations up to 600 mM, the FT preparation synthesized 1-kestose at all concentrations, and synthesized 6-kestose at concentrations of 150 mM and greater. The K-m of 1-kestose production was 0.2 M. When the FT preparation was assayed at a concentration of activity approximately half that measured in fresh tissue with 100 mM sucrose, 1-kestose, or 6(G)-kestose as substrates, fructans of degree of polymerization (DP) less than or equal to 5 were synthesized. A partially purified FFT activity, free of SST and invertase activities, which synthesized beta-2,1-glycosidic linked oligofructans of DP less than or equal to 6, was combined in vitro with the FT preparation (FFT-FT preparation) to give a ratio of SST:FFT activities similar to that measured in crude enzyme extracts from L. rigidum. The FFT-FT preparation synthesized oligofructans when assayed with 100 mM concentrations of sucrose, 1-kestose or 6(G)-kestose, but was not able to synthesize fructans of DP greater than or equal to 6 even after extended assays of up to 10 h. The FFT-FT preparation was also assayed with 100 mM sucrose with small amounts of concentrated sucrose added periodically during the assay to maintain the substrate concentration. In this assay, the FFT-FT preparation synthesized fructans up to an apparent DP of 17 or greater. The fructans of DP greater than or equal to 6 synthesized in the assay appeared to form two molecular series containing both beta-2,1- and beta-2,6-glycosidic linked fructosyl residues with terminal or internal glucosyl residues. The apparent rate of SST activity in the assay of the FFT-FT preparation was greater than that measured in a similar assay of the FT preparation alone which did not result in fructans with DP greater than or equal to 6. It was concluded that the FFT-FT preparation, when assayed with a continual supply of sucrose, contained a factor which promoted synthesis of fructans of DP greater than or equal to 6 and synthesis of beta-2,B-glycosidic linkages between fructosyl residues.

Biochemical synthesis, purification and preliminary pharmacological evaluation of normorphine-3-glucuronide

Normorphine was synthesised from morphine by thermal decomposition of an N-alpha-chloroethylchloroformate adduct, and purified (> 98% purity) using semipreparative HPLC with ultraviolet detection. Normorphine-3-glucuronide (NM3G) was biochemically synthesised using the substrate normorphine, uridine diphosphoglucuronic acid and Sprague-Dawley rat liver microsomes in a 75% yield (relative to normorphine base). The synthesised NM3G was purified by precipitation and washing with acetonitrile. Determinations of purity using HPLC with electrochemical and ultraviolet detection confirmed that the NM3G produced was of high (> 99%) purity. Mass spectrometry, fourier transform infrared spectrophotometry and nuclear magnetic resonance spectrometry confirmed the structure, especially placement of the glucuronide moiety at the 3-phenolic position and not at the 17-nitrogen. Administration of NM3G by the intracerebroventricular (icy) route to rats in doses of 2.5 and 7.5 mu g resulted in the development of central nervous system (CNS) excitatory behavioural effects including myoclonus, chewing, wet-dog shakes, ataxia and explosive motor behaviour. At an icy dose of 7.5 mu g, NM3G also induced short periods of tonic-clonic convulsive activity. Thus, NM3G elicits CNS excitation following supraspinal administration in a manner analogous to morphine-3-glucuronide (M3G), the major metabolite of morphine (1). Further studies are required to determine whether NM3G attenuates morphine-induced antinociception in se similar manner to M3G.

Effects of Optimal Medical Treatment With or Without Coronary Revascularization on Angina and Subsequent Revascularizations in Patients With Type 2 Diabetes Mellitus and Stable Ischemic Heart Disease

Background-In the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, an initial strategy of coronary revascularization and optimal medical treatment (REV) compared with an initial optimal medical treatment with the option of subsequent revascularization (MED) did not reduce all-cause mortality or the composite of cardiovascular death, myocardial infarction, and stroke in patients with type 2 diabetes mellitus and stable ischemic heart disease. In the same population, we tested whether the REV strategy was superior to the MED strategy in preventing worsening and new angina and subsequent coronary revascularizations. Methods and Results-Among the 2364 men and women (mean age, 62.4 years) with type 2 diabetes mellitus, documented coronary artery disease, and myocardial ischemia, 1191 were randomized to the MED and 1173 to the REV strategy preselected in the percutaneous coronary intervention (796) and coronary artery bypass graft (377) strata. Compared with the MED strategy, the REV strategy at the 3-year follow-up had a lower rate of worsening angina (8% versus 13%; P < 0.001), new angina (37% versus 51%; P = 0.001), and subsequent coronary revascularizations (18% versus 33%; P < 0.001) and a higher rate of angina-free status (66% versus 58%; P = 0.003). The coronary artery bypass graft stratum patients were at higher risk than those in the percutaneous coronary intervention stratum, and had the greatest benefits from REV. Conclusions-In these patients, the REV strategy reduced the occurrence of worsening angina, new angina, and subsequent coronary revascularizations more than the MED strategy. The symptomatic benefits were observed particularly for high-risk patients.