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1.
Adv Exp Med Biol ; 1421: 15-35, 2023.
Article in English | MEDLINE | ID: mdl-37524982

ABSTRACT

Cadaveric anatomy is frequently described as the gold standard for anatomy education. Increasingly and especially following the COVID-19 pandemic, there is acceptance that a blended approach for anatomy curriculum delivery is optimal for learners.Setting up a new UK Medical School in 2019 necessitated building a new cadaveric anatomy facility. To enable anatomy curriculum delivery during the construction period (2019-2021), a technology-enhanced learning (TEL) anatomy curriculum was developed, as well as an anatomy laboratory suitable for TEL. Development of a TEL anatomy curriculum with the later inclusion of cadaveric anatomy is unusual since the typical model is to supplement cadaveric anatomy with TEL approaches.TEL solutions that provide digital visualisation of anatomy may support learners by reducing cognitive load. Examples include using colour and/or translucency features to highlight and signpost pertinent anatomy and constructing virtual anatomical models in real time, rather than dissection. Radiology and portable ultrasound provide clinically contextualised visualisations of anatomy; the latter offers a haptic learning experience too. A TEL anatomy laboratory can provide interactive learning experiences for engagement and outreach activities for young school children, where cadaveric anatomy is not suitable.


Subject(s)
COVID-19 , Education, Medical, Undergraduate , Students, Medical , Humans , Pandemics , Curriculum , Cadaver , Students, Medical/psychology
2.
Br J Surg ; 108(1): 14-23, 2021 01 27.
Article in English | MEDLINE | ID: mdl-33640918

ABSTRACT

BACKGROUND: The optimal choice for mesh fixation in laparoscopic inguinal hernia repair (LIHR) has not been well established. This review compared the effects of glue versus mechanical mesh fixation in LIHR on incidence of chronic postoperative inguinal pain (CPIP) and other secondary outcomes, including acute pain, seroma, haematoma, hernia recurrence and other postoperative complications. METHODS: A systematic review of English/non-English studies using MEDLINE, the Cochrane Library, OpenGrey, OpenThesis and Web of Science, and searching bibliographies of included studies was completed. Search terms included laparoscopic, hernia, fibrin glue, Tisseel, Tissucol, cyanoacrylate, Glubran and Liquiband. Only RCTs comparing mechanical with glue-based fixation in adult patients (aged over 18 years) that examined CPIP were included. Two authors independently completed risk-of-bias assessment and data extraction against predefined data fields. All pooled analyses were computed using a random-effects model. RESULTS: Fifteen RCTs met the inclusion criteria; 2777 hernias among 2109 patients were assessed. The incidence of CPIP was reduced with use of glue-based fixation (risk ratio (RR) 0.36, 95 per cent c.i. 0.19 to 0.69; P = 0.002), with moderate heterogeneity that disappeared with sensitivity analysis (8 d.f.) for patient-blinded studies (RR 0.43, 0.27 to 0.86). Trial sequential analysis provided evidence for a relative risk reduction of at least 25 per cent. The incidence of haeamtoma was reduced by using glue-based fixation (RR 0.29, 0.10 to 0.82; P = 0.02) with no significant effects on seroma formation or hernia recurrence (RR 1.07, 0.46 to 2.47; P = 0.88). CONCLUSION: Glue-based mesh fixation appears to reduce the incidence of CPIP and haematoma after LIHR compared with mechanical fixation, with comparable recurrence rates.


Subject(s)
Adhesives/therapeutic use , Hernia, Inguinal/surgery , Herniorrhaphy/methods , Laparoscopy/methods , Surgical Mesh , Herniorrhaphy/instrumentation , Humans , Laparoscopy/instrumentation , Pain, Postoperative/epidemiology , Randomized Controlled Trials as Topic
3.
Ann R Coll Surg Engl ; 101(4): e96-e98, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30773901

ABSTRACT

Lumbar hernias can be superior (Grynfelt) and inferior (Petit). Inferior lumbar hernias are extremely rare and, therefore, are associated with diagnostic difficulty. We present a case of a primary spontaneous inferior lumbar hernia in a 79-year-old woman that was initially diagnosed as a large lipoma on ultrasound. The first operation was abandoned and an open mesh repair was conducted. Lumbar hernias can be primary acquired (55%), secondary acquired (25%) or congenital (20%). Cross-sectional imaging by CT or MRI appears to be the gold standard in diagnosis as ultrasound may lead to misdiagnosis. Strangulation, incarceration and obstruction are recognised complications, requiring prompt surgical intervention. There are currently no guidelines for surgical managements, although laparoscopic surgery may give the best results. In view of the scarcity of published cases, we aim to add to the literature to raise the index of suspicion and to promote prompt surgical management of lumbar hernias.


Subject(s)
Hernia, Abdominal/diagnosis , Lipoma/diagnosis , Aged , Diagnostic Errors , Female , Hernia, Abdominal/diagnostic imaging , Hernia, Abdominal/surgery , Humans , Lumbosacral Region , Tomography, X-Ray Computed
4.
Arch Biochem Biophys ; 663: 239-248, 2019 03 15.
Article in English | MEDLINE | ID: mdl-30659802

ABSTRACT

Mitochondrial reactive oxygen species (ROS) are important cellular signaling molecules, but can cause oxidative damage if not kept within tolerable limits. An important proximal form of ROS in mitochondria is superoxide. Its production is thought to occur in regulated stochastic bursts, but current methods using mitochondrial targeted cpYFP to assess superoxide flashes are confounded by changes in pH. Accordingly, these flashes are generally referred to as 'mitoflashes'. Here we provide regulatory insights into mitoflashes and pH fluctuations in skeletal muscle, and the role of uncoupling protein-3 (UCP3). Using quantitative confocal microscopy of mitoflashes in intact muscle fibers, we show that the mitoflash magnitude significantly correlates with the degree of mitochondrial inner membrane depolarization and ablation of UCP3 did not affect this correlation. We assessed the effects of the absence of UCP3 on mitoflash activity in intact skeletal muscle fibers, and found no effects on mitoflash frequency, amplitude or duration, with a slight reduction in the average size of mitoflashes. We further investigated the regulation of pH flashes (pHlashes, presumably a component of mitoflash) by UCP3 using mitochondrial targeted SypHer (mt-SypHer) in skeletal muscle fibers. The frequency of pHlashes was significantly reduced in the absence of UCP3, without changes in other flash properties. ROS scavenger, tiron, did not alter pHlash frequency in either WT or UCP3KO mice. High resolution respirometry revealed that in the absence of UCP3 there is impaired proton leak and Complex I-driven respiration and maximal coupled respiration. Total cellular production of hydrogen peroxide (H2O2) as detected by Amplex-UltraRed was unaffected. Altogether, we demonstrate a correlation between mitochondrial membrane potential and mitoflash magnitude in skeletal muscle fibers that is independent of UCP3, and a role for UCP3 in the control of pHlash frequency and of proton leak- and Complex I coupled-respiration in skeletal muscle fibers. The differential regulation of mitoflashes and pHlashes by UCP3 and tiron also indicate that the two events, though may be related, are not identical events.


Subject(s)
Hydrogen-Ion Concentration , Mitochondria, Muscle/metabolism , Muscle, Skeletal/metabolism , Uncoupling Protein 3/physiology , Animals , Energy Metabolism , Membrane Potential, Mitochondrial , Mice , Mice, Inbred C57BL , Oxygen Consumption , Uncoupling Protein 3/genetics
5.
Biochim Biophys Acta Gen Subj ; 1863(2): 395-407, 2019 02.
Article in English | MEDLINE | ID: mdl-30448294

ABSTRACT

BACKGROUND: IL-15 is believed to play a role in the beneficial impact of exercise on muscle energy metabolism. However, previous studies have generally used supraphysiological levels of IL-15 that do not represent contraction-induced IL-15 secretion. METHODS: L6 myotubes were treated acutely (3 h) and chronically (48 h) with concentrations of IL-15 mimicking circulating (1-10 pg/ml) and muscle interstitial (100 pg/ml -20 ng/ml) IL-15 levels with the aim to better understand its autocrine/paracrine role on muscle glucose uptake and mitochondrial function. RESULTS: Acute exposure to IL-15 levels representing muscle interstitial IL-15 increased basal glucose uptake without affecting insulin sensitivity. This was accompanied by increased mitochondrial oxidative functions in association with increased AMPK pathway and formation of complex III-containing supercomplexes. Conversely, chronic IL-15 exposure resulted in a biphasic effect on mitochondrial oxidative functions and ETC supercomplex formation was increased with low IL-15 levels but decreased with higher IL-15 concentrations. The AMPK pathway was activated only by high levels of chronic IL-15 treatment. Similar results were obtained in skeletal muscle from muscle-specific IL-15 overexpressing mice that show very high circulating IL-15 levels. CONCLUSIONS: Acute IL-15 treatment that mimics local IL-15 concentrations enhances muscle glucose uptake and mitochondrial oxidative functions. That mitochondria respond differently to different levels of IL-15 during chronic treatments indicates that IL-15 might activate two different pathways in muscle depending on IL-15 concentrations. GENERAL SIGNIFICANCE: Our results suggest that IL-15 may act in an autocrine/paracrine fashion and be, at least in part, involved in the positive effect of exercise on muscle energy metabolism.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Cell Respiration/drug effects , Glucose/metabolism , Interleukin-15/pharmacology , Mitochondria/drug effects , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Electron Transport/drug effects , Interleukin-15/genetics , Mice , Mice, Transgenic , Mitochondria/metabolism , Oxidation-Reduction , Rats
6.
Int J Obes (Lond) ; 42(3): 353-362, 2018 03.
Article in English | MEDLINE | ID: mdl-29151592

ABSTRACT

BACKGROUND/OBJECTIVES: Inter-individual variability in weight loss during obesity treatment is complex and poorly understood. Here we use whole body and tissue approaches to investigate fuel oxidation characteristics in skeletal muscle fibers, cells and distinct circulating protein biomarkers before and after a high fat meal (HFM) challenge in those who lost the most (obese diet-sensitive; ODS) vs the least (obese diet-resistant; ODR) amount of weight in a highly controlled weight management program. SUBJECTS/METHODS: In 20 weight stable-matched ODS and ODR women who previously completed a standardized clinical weight loss program, we analyzed whole-body energetics and metabolic parameters in vastus lateralis biopsies and plasma samples that were obtained in the fasting state and 6 h after a defined HFM, equivalent to 35% of total daily energy requirements. RESULTS: At baseline (fasting) and post-HFM, muscle fatty acid oxidation and maximal oxidative phosphorylation were significantly greater in ODS vs ODR, as was reactive oxygen species emission. Plasma proteomics of 1130 proteins pre and 1, 2, 5 and 6 h after the HFM demonstrated distinct group and interaction differences. Group differences identified S-formyl glutathione hydratase, heat shock 70 kDA protein 1A/B (HSP72), and eukaryotic translation initiation factor 5 (eIF5) to be higher in ODS vs ODR. Group-time differences included aryl hydrocarbon interacting protein (AIP), peptidylpropyl isomerase D (PPID) and tyrosine protein-kinase Fgr, which increased in ODR vs ODS over time. HSP72 levels correlated with muscle oxidation and citrate synthase activity. These proteins circulate in exosomes; exosomes isolated from ODS plasma increased resting, leak and maximal respiration rates in C2C12 myotubes by 58%, 21% and 51%, respectively, vs those isolated from ODR plasma. CONCLUSIONS: Findings demonstrate distinct muscle metabolism and plasma proteomics in fasting and post-HFM states corresponding in diet-sensitive vs diet-resistant obese women.


Subject(s)
Blood Proteins/metabolism , Muscle Fibers, Skeletal/metabolism , Obesity , Proteome/metabolism , Biomarkers/blood , Blood Proteins/analysis , Case-Control Studies , Diet , Exosomes/metabolism , Female , Humans , Middle Aged , Muscle, Skeletal/metabolism , Muscle, Skeletal/physiopathology , Obesity/blood , Obesity/diet therapy , Obesity/epidemiology , Obesity/metabolism , Proteome/analysis , Treatment Failure
7.
Anaesthesia ; 71(9): 1064-9, 2016 09.
Article in English | MEDLINE | ID: mdl-27440171

ABSTRACT

The serratus anterior plane block has been described for analgesia of the hemithorax. This study was conducted to determine the spread of injectate and investigate the anatomical basis of the block. Ultrasound-guided serratus anterior plane block was performed on six soft-fix embalmed cadavers. All cadavers received bilateral injections, on one side performed with 20 ml latex and on the other with 20 ml methylene blue. Subsequent dissection explored the extent of spread and nerve involvement. Photographs were taken throughout dissection. The intercostal nerves were involved on three occasions with dye, but not with latex. The lateral cutaneous branches of the intercostal nerve contained dye and latex on all occasions. The serratus plane block appears to be mediated through blockade of the lateral cutaneous branches of the intercostal nerves. Anatomically, serratus plane block does not appear to be equivalent to paravertebral block for rib fracture analgesia.


Subject(s)
Intercostal Nerves/anatomy & histology , Methylene Blue/administration & dosage , Nerve Block/methods , Thoracic Wall/innervation , Ultrasonography, Interventional/methods , Cadaver , Humans , Intercostal Nerves/diagnostic imaging
8.
Breast ; 24(4): 318-20, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25800381

ABSTRACT

The advent of sentinel lymph node biopsy has revolutionised surgical management of axillary nodal disease in patients with breast cancer. Patients undergoing neo-adjuvant chemotherapy for large breast primary tumours may experience complete pathological response on a previously positive sentinel node whilst not eliminating the tumour from the other lymph nodes. Results from 2 large prospective cohort studies investigating sentinel lymph node biopsy after neo-adjuvant chemotherapy demonstrate a combined false negative rate of 12.6-14.2% and identification rate of 80-89% with the minimal acceptable false negative rate and identification rate being set at 10% and 90%, respectively. A false negative rate of 14% would have been classified as unacceptable when compared to the figures obtained by the pioneers of sentinel lymph node biopsy which was 5% or less.


Subject(s)
Breast Neoplasms/pathology , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy/statistics & numerical data , Axilla , Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant , False Negative Reactions , Female , Humans , Lymphatic Metastasis , Neoadjuvant Therapy , Prospective Studies , Sentinel Lymph Node Biopsy/methods
9.
Benef Microbes ; 6(4): 457-71, 2015.
Article in English | MEDLINE | ID: mdl-25567540

ABSTRACT

Lactic acid bacteria, such as those of the Lactobacillus genus, naturally reside within the microbiota of the human body and have long been used as starter cultures and probiotic enhancers in fermented foods, such as fermented drinks, yoghurts and cheeses. Many of the beneficial qualities of these bacteria have traditionally been associated with the bacteria themselves, however, a recent spate of studies have demonstrated a wide variety of biological effects exhibited by lactobacilli-produced exopolysaccharides which could, theoretically, confer a range of local and systemic health benefits upon the host. In this review, we discuss the production of exopolysaccharides within the Lactobacillus genus and explore their potential as beneficial bioactive compounds.


Subject(s)
Immunologic Factors/metabolism , Immunologic Factors/pharmacology , Lactobacillus/metabolism , Polysaccharides, Bacterial/metabolism , Polysaccharides, Bacterial/pharmacology , Humans
10.
Int J Surg Case Rep ; 2(6): 86-9, 2011.
Article in English | MEDLINE | ID: mdl-22096691

ABSTRACT

Haemangiomas are one of the most common soft tissue tumours comprising 7% of all benign tumours. Vascular malformations are often confused with haemangiomas. The etiology is unknown. They are common in infancy and childhood and females are more commonly affected. These tumours may be superficial or deep, and deeply seated lesions, are difficult to diagnose clinically and hence require radiographic assessment. Deep-seated haemangiomas are usually intramuscular, although intra-articular synovial haemangiomas also occur. The commonest anatomic site is the lower limb.Despite their vascular origin, haemangiomas do not metastasize or undergo malignant transformation. Many treatment modalities for the symptomatic haemangioma are available but surgical excision is the preferred treatment. We present an unusual case of a dumb-bell intramuscular haemangioma involving the triceps and extending into the cubital tunnel of the elbow, distinguish between haemangiomas and vascular malformations and emphasize the importance of surgical technique in ensuring ulnar nerve safety.

11.
J Vis Exp ; (58)2011 Dec 20.
Article in English | MEDLINE | ID: mdl-22214879

ABSTRACT

Pain is an unpleasant sensory and emotional experience. Since infants cannot verbally report their experiences, current methods of pain assessment are based on behavioural and physiological body reactions, such as crying, body movements or changes in facial expression. While these measures demonstrate that infants mount a response following noxious stimulation, they are limited: they are based on activation of subcortical somatic and autonomic motor pathways that may not be reliably linked to central sensory processing in the brain. Knowledge of how the central nervous system responds to noxious events could provide an insight to how nociceptive information and pain is processed in newborns. The heel lancing procedure used to extract blood from hospitalised infants offers a unique opportunity to study pain in infancy. In this video we describe how electroencephalography (EEG) and electromyography (EMG) time-locked to this procedure can be used to investigate nociceptive activity in the brain and spinal cord. This integrative approach to the measurement of infant pain has the potential to pave the way for an effective and sensitive clinical measurement tool.


Subject(s)
Electroencephalography/methods , Electromyography/methods , Nociception/physiology , Pain Measurement/methods , Pain/diagnosis , Brain/physiopathology , Humans , Infant , Pain/physiopathology , Spinal Cord/physiopathology
12.
Med Teach ; 32(2): e101-5, 2010.
Article in English | MEDLINE | ID: mdl-20163215

ABSTRACT

BACKGROUND: A number of studies have explored student attitudes to examining each other (peer physical examination: PPE). Differences have emerged in whether students prefer to be examined by friends or strangers. Changes have been reported in how students feel about PPE if asked before or after the PPE programme commences. RESEARCH INTENTION: Since a Grounded Theory paradigm was employed, there was no formal research hypothesis: the research intention was to explore factors which might underlie changes in student willingness to undertake PPE following familiarity with the process. METHODS: Students who had completed an Examining Fellow Students Questionnaire at the beginning and end of the academic year, and who had indicated a change in willingness to participate, were invited to attend focus groups. Four focus groups were convened and transcripts were analysed for common themes. RESULTS: Surprisingly, students downplayed the significance of changes. Also unexpectedly, dichotomous views emerged on familiarity, with some students preferring friends for examination and others preferring strangers. Staff embarrassment also emerged as a factor inhibiting student participation. CONCLUSIONS: The significance of reported changes in attitudes to PPE may have been exaggerated. Proposals for increasing the willingness of students to participate in PPE are developed from the emergent themes.


Subject(s)
Attitude of Health Personnel , Internship and Residency/methods , Peer Group , Physical Examination/methods , Students, Medical/psychology , Cultural Characteristics , Female , Humans , Interprofessional Relations , Male , Sex Factors
13.
Clin Anat ; 22(6): 684-8, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19637299

ABSTRACT

The percutaneous placement of lateral distal humeral pins risks injury to the radial nerve. We aimed to provide a reliable and safe parameter for the insertion of lateral distal humeral pins. A secondary aim of this study was to investigate the effect of pin/screw placement in the intended zone of fixation at the lateral distal humerus. We dissected 70 fresh cadaveric upper limbs and the radial nerve was identified and its course followed into the anterior compartment. The point where the radial nerve crosses humerus in mid lateral plane was identified and the distance between this point and lateral epicondyle was measured, as was the maximum trans-epicondylar distance, along with the olecranon fossa height. Statistical analysis was performed using the Pearson correlation coefficient. The average trans-epicondylar distance was measured at 62 +/- 6 mm (range 52-78 mm), and the average lateral radial nerve height was 102 +/- 10 mm (range 75-129 mm). The ratio of the lateral nerve height to the trans-epicondylar distance was an average of 1.7 +/- 0.2 (range 1.4-2.0). The Pearson correlation coefficient between the lateral nerve height and the trans-epicondylar distance was r = 0.95. A relative dimension, the trans-epicondylar distance is both reliable and easily accessible to the operating surgeon. The absolute safe zone for pin entry into the lateral distal humerus is that area lying within the caudad 70% of a line, equivalent in length to the patient's own trans-epicondylar distance, when projected proximally from the lateral epicondyle.


Subject(s)
Bone Nails , Bone Screws , Elbow Joint/innervation , Orthopedic Procedures/methods , Radial Nerve/anatomy & histology , Aged , Aged, 80 and over , Elbow Joint/surgery , Female , Humans , Humerus/anatomy & histology , Humerus/surgery , Male , Middle Aged , Orthopedic Procedures/adverse effects , Orthopedic Procedures/instrumentation , Pilot Projects , Postoperative Complications/prevention & control
14.
Clin Exp Pharmacol Physiol ; 28(5-6): 451-8, 2001.
Article in English | MEDLINE | ID: mdl-11380521

ABSTRACT

1. Pharmacological evidence suggests that some of the clinical actions of propofol may be mediated, at least in part, by positive modulation of the GABA(A) receptor chloride channel. The effect of propofol at other native neuronal ligand-gated ion channels is unclear. 2. To gain some insight into the effects of propofol at a range of native neuronal receptors, the present study has used an extracellular recording technique and determined its effects at GABA(A), 5-HT3, P2X and nicotinic acetylcholine (nACh) receptors of the rat isolated vagus nerve and the GABA(A) and strychnine-sensitive glycine receptor of the rat isolated optic nerve. In addition, we have used patch-clamp recording techniques to further investigate the effects of propofol at the GABA(A) and strychnine-sensitive glycine receptors in rat cultured hippocampal neurons. 3. Propofol (0.3-100 micromol/L) concentration-dependently potentiated submaximal GABA-evoked responses in the vagus nerve and shifted the GABA concentration-response curve to the left. In contrast, propofol at concentrations ranging from 1 to 10 micromol/L had little or no effect on 5-HT3, P2X or nACh receptor-mediated responses in the vagus nerve but, at 100 micromol/L, propofol inhibited these responses to approximately 50% of control. In the optic nerve, EC20 GABA-evoked responses were also potentiated by propofol (10 micromol/L), while EC20 glycine-evoked responses were minimally enhanced. 4. Further investigations using cultured hippocampal neurons showed that submaximal (10 micromol/L) GABA-evoked currents were potentiated by propofol (1-10 micromol/L), in a non-voltage-dependent manner, whereas submaximal (100 micromol/L) glycine-evoked currents were unaffected. 5. These data suggest that propofol, at therapeutic concentrations, exerts its principle pharmacological actions at GABA(A) receptors with relatively little effect at other neuronal ligand-gated ion channels.


Subject(s)
Anesthetics, Intravenous/pharmacology , Ion Channel Gating/drug effects , Neurons/metabolism , Propofol/pharmacology , Animals , Cells, Cultured , Electrophysiology , Ligands , Male , Neurons/drug effects , Optic Nerve/cytology , Optic Nerve/drug effects , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Rats, Wistar , Receptors, Cholinergic/drug effects , Receptors, Glycine/drug effects , Receptors, Purinergic P2/drug effects , Receptors, Serotonin/drug effects , Receptors, Serotonin, 5-HT3 , Vagus Nerve/cytology , Vagus Nerve/drug effects , gamma-Aminobutyric Acid/pharmacology
15.
Toxicon ; 39(2-3): 309-17, 2001.
Article in English | MEDLINE | ID: mdl-10978749

ABSTRACT

A new insecticidal toxin Tx4(5-5) was isolated from the fraction PhTx4 of the venom of the spider Phoneutria nigriventer by reverse phase high performance liquid chromatography (HPLC) and anion exchange HPLC. The complete amino acid sequence determined by automated Edman degradation showed that Tx4(5-5) is a single chain polypeptide composed of 47 amino acid residues, including 10 cysteines, with a calculated molecular mass of 5175 Da. Tx4(5-5) shows 64% of sequence identity with Tx4(6-1), another insecticidal toxin from the same venom. Tx4(5-5) was highly toxic to house fly (Musca domestica), cockroach (Periplaneta americana) and cricket (Acheta domesticus ), producing neurotoxic effects (knock-down, trembling with uncoordinated movements) at doses as low as 50 ng/g (house fly), 250 ng/g (cockroach) and 150 ng/g (cricket). In contrast, intracerebroventricular injections (30 microg) into mice induced no behavioural effects. Preliminary electrophysiological studies carried out on whole-cell voltage-clamped rat hippocampal neurones indicated that Tx4(5-5) (at 1 microM) reversibly inhibited the N-methyl-D-aspartate-subtype of ionotropic glutamate receptor, while having little or no effect on kainate-, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid- or gamma-aminobutyric acid-activated currents.


Subject(s)
Insecticides/isolation & purification , Neurotoxins/isolation & purification , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Spider Venoms/isolation & purification , Spider Venoms/toxicity , Amino Acid Sequence , Animals , Cell Membrane/drug effects , Cells, Cultured , Chromatography, High Pressure Liquid , Cockroaches , Electrophoresis, Polyacrylamide Gel , Gryllidae , Hippocampus/drug effects , Insecticides/toxicity , Lethal Dose 50 , Mice , Molecular Sequence Data , Neurotoxins/toxicity , Patch-Clamp Techniques , Rats
16.
J Voice ; 13(2): 203-18, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10442750

ABSTRACT

Botox injection into the thyroarytenoid muscle is thought to alter the glottal competence and laryngeal adduction of patients with adductor spasmodic dysphonia (ADSD). Hypofunctional responses to treatment have been rated subjectively and inferred from postinjection breathy voice, aphonia, midline glottal gap, or subclinical aspiration. Clinical experience suggests that temporary hypofunction varies in duration and severity among patients. This study used electroglottographic measures to examine changes over time in glottal competence during the relatively stable phonation produced by 5 patients with ADSD. Hierarchical linear modeling was used to test 3 hypotheses: (a) that reduced laryngeal adduction would occur during the first 3 weeks postinjection, followed by a reversal; (b) that patients' hypofunctional response curves would differ one from another; and (c) that changes in adduction, if present, would be related to changes in severity ratings of ADSD symptoms. For 3 participants, significant hypoadduction occurred after injection and reversed toward preinjection level over an 8-week period. Two participants demonstrated a flat or increasing vocal fold contact response curve during the early postinjection period. Observations were consistent with the previously reported differences and possibly complex relation between the resolution of breathy hypofunction and ultimate return of ADSD symptoms.


Subject(s)
Botulinum Toxins, Type A/therapeutic use , Neuromuscular Agents/therapeutic use , Phonation/drug effects , Voice Disorders/drug therapy , Adult , Aged , Electric Stimulation/methods , Electromyography/methods , Female , Humans , Male , Middle Aged , Severity of Illness Index , Time Factors , Treatment Outcome , Voice Disorders/diagnosis , Voice Quality/drug effects
17.
Eur J Neurosci ; 11(8): 2897-905, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10457186

ABSTRACT

Mefenamic acid (MFA) has anti-convulsant and pro-convulsant effects in vivo, and has been shown to potentiate and inhibit GABAA (gamma-aminobutyric acid) receptors in vitro. In this study, whole-cell currents were recorded from Xenopus oocytes and human embryonic kidney (HEK) cells expressing human recombinant GABAA receptors to resolve the molecular mechanisms by which MFA modulates GABAA receptor function. We demonstrate that MFA potentiated GABA-activated currents for alpha1beta2 gamma2S (EC50 = 3.2 +/- 0.5 microM), but not for alpha1beta1 gamma2S receptors. MFA also enhanced GABA-activated responses and directly activated alpha1beta2/beta3 GABAA receptors, but inhibited responses to GABA on alpha1beta1 constructs (IC50 = 40 +/- 7.2 microM). A comparison of beta1, beta2 and beta3 subunits suggested that the positive modulatory action of MFA involved asparagine (N) 290 in the second transmembrane domain (TM2) of the beta2 and beta3 subunits. Mutation of N290 to serine (S) markedly reduced modulation by MFA in alpha1beta2(N290S)gamma2S receptors, whereas alpha1beta1(S290N)gamma2S constructs revealed potentiated responses to GABA (EC50 = 7.8 +/- 1.7 microM) and direct activation by MFA. The potentiation by MFA displayed voltage sensitivity. The direct activation, potentiation and inhibitory aspects of MFA action were predominantly conferred by the beta subunits as the spontaneously active homomeric beta1 and beta3 receptors were susceptible to modulation by MFA. Molecular comparisons of MFA, loreclezole and etomidate, agents which exhibit similar selectivity for GABAA receptors, revealed their ability to adopt similar structural conformations. This study indicates that N290 in TM2 of beta2 and beta3 subunits is important for the regulation of GABAA receptor function by MFA. Our data provide a potential molecular mechanism for the complex central effects of MFA in vivo.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Mefenamic Acid/pharmacology , Receptors, GABA-A/drug effects , Receptors, GABA-A/metabolism , Amino Acid Sequence/genetics , Amino Acid Sequence/physiology , Animals , Cell Line/physiology , Electric Conductivity , Electrophysiology , Etomidate/chemistry , Humans , Mefenamic Acid/chemistry , Models, Molecular , Molecular Conformation , Oocytes/metabolism , Oocytes/physiology , Protein Isoforms/drug effects , Protein Isoforms/physiology , Receptors, GABA-A/genetics , Receptors, GABA-A/physiology , Recombinant Proteins/drug effects , Recombinant Proteins/metabolism , Triazoles/chemistry , Triazoles/pharmacology , Xenopus laevis
18.
J Oral Pathol Med ; 26(3): 105-9, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9083933

ABSTRACT

To determine whether the T-cell inflammatory infiltrate in oral lichen planus (OLP) represents a selective activation and expansion of a limited repertoire of T-cell receptor (TCR) specific T-cells, V beta gene expression was investigated in lesional T-lymphocytes in OLP. A reverse transcriptase-polymerase chain reaction (RT-PCR) technique was used to amplify the 24 major V beta gene sub-families of infiltrating mucosal lymphocytes and peripheral blood mononuclear cells (PMNC) in seven patients with reticular OLP and four healthy control patients. Specificity of amplified products was confirmed by Southern blotting with a C beta internal probe. TCR V beta usage by lesional T-cells in OLP was markedly heterogeneous 5-23 V beta sub-families). In 6/8 patients with OLP, V beta usage was restricted with < or = 20/25 sub-families detected; only one of the V beta sub-families (V beta 8) was present in all of the OLP patients demonstrating TCR V beta restriction. In contrast, TCR V beta usage was unrestricted in PMNC from OLP patients and controls (> or = 23/ 25 sub-families detected). In three patients, certain V beta sub-families (V beta 13, V beta 14 & V beta 15) were present in the lesional T-cell population but were under-represented in PMNC. These results suggest a selective V beta gene usage by lesional infiltrating T-cells in oral lichen planus. The non-uniformity of V beta restriction in lesional T-cells does not support the concept of a common superantigen in OLP and reflects the heterogeneity of the disease.


Subject(s)
Lichen Planus, Oral/pathology , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes/metabolism , Adult , Aged , Blotting, Southern , Female , Gene Amplification , Gene Expression Regulation , Humans , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/pathology , Lichen Planus, Oral/genetics , Lymphocyte Activation , Male , Middle Aged , Mouth Mucosa/metabolism , Mouth Mucosa/pathology , Polymerase Chain Reaction , RNA-Directed DNA Polymerase , Receptors, Antigen, T-Cell/classification , Superantigens/analysis , Superantigens/genetics
19.
Environ Monit Assess ; 36(1): 27-43, 1995 May.
Article in English | MEDLINE | ID: mdl-24197674

ABSTRACT

Using analyses from honey mesquite (Prosopis glandulosa) leaves from nearly pristine locations in Arizona, an inorganic plant concentration standard is proposed for use as a 'Sonoran Reference Plant' (SRP). Such a standard can be used as a monitoring device for different anthropogenic pollution sources throughout the Sonoran Desert. To test the application of the SRP, honey mesquite leaves were collected at different sites in southern Arizona and their 'chemical fingerprints' compared to SRP. Sources of element origin were identified through factor analysis and correlation matrices. A terrestrial factor was found in leaves from all sites. Anthropogenic factors varied for different sites. Mesquite leaves accumulated significant amounts of elements originating from copper smelters (As, Sb) and urban pollution (La, Sm, Ce, V). These pollutants are small-sized and have been linked to human lung diseases. Mesquite is a deciduous tree; the yearly comparison of mesquite leaf element concentration spectra to the SRP standard can be used to determine seasonal improvement or deterioration of environmental quality in a particular area.

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