Adrian P. Harrison

The exposure to and health effects of antimony

Context: This minireview describes the health effects of antimony exposure in the workplace and the environment. Aim: To collate information on the consequences of occupational and environmental exposure to antimony on physiological function and well-being. Methods: The criteria used in the current minireview for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability and Health. Articles were classified from an acute and chronic exposure and toxicity thrust. Results: The proportion of utilised and non-utilised articles was tabulated. Antimony toxicity is dependent on the exposure dose, duration, route (breathing, eating, drinking, or skin contact), other chemical exposures, age, sex, nutritional status, family traits, life style, and state of health. Chronic exposure to antimony in the air at levels of 9 mg/m3 may exacerbate irritation of the eyes, skin, and lungs. Long-term inhalation of antimony can potentiate pneumoconiosis, altered electrocardiograms, stomach pain, diarrhea, vomiting, and stomach ulcers, results which were confirmed in laboratory animals. Although there were investigations of the effect of antimony in sudden infant death syndrome, current findings suggest no link. Antimony trioxide exposure is predominant in smelters. Mining and exposure via glass working, soldering, and brazing are also important. Conclusion: Antimony has some useful but undoubtedly harmful effects on health and well-being and measures need to be taken to prevent hazardous exposure of the like. Its biological monitoring in the workplace is essential.

Vesicular glutamate transporter 2 (VGLUT2) is co-stored with PACAP in projections from the rat melanopsin-containing retinal ganglion cells

The retinal ganglion cell layer of the eye comprises a subtype of cells characterized by their intrinsic photosensitivity and expression of melanopsin (ipRGCs). These cells regulate a variety of non-image-forming (NIF) functions such as light entrainment of circadian rhythms, acute suppression of locomotor activity (masking), and pupillary light reflex. Two neurotransmitters have been identified in ipRGCs, glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP). To date, little is known about their release and interplay. Here, we describe the presence and co-localization of vesicular glutamate transporter 2 (VGLUT2; a marker of glutamate signaling) and PACAP in ipRGCs and their projections in the brain. Nine adult male Wistar rats were assigned to one of three groups; anterograde tracing (n = 3), eye enucleation (n = 3), and untreated (n = 3). Under anaesthesia, rats were transcardially perfusion-fixated, after which the brains and eyes were removed for double immunohistochemical staining using a polyclonal anti-VGLUT2 antibody and a mouse monoclonal anti-PACAP antibody. Results revealed that VGLUT2- and PACAP-immunoreactivity (-ir) were present in ipRGCs and co-localized in their projections in the suprachiasmatic nucleus, the intergeniculate leaflet, and the olivary pretectal nucleus. We conclude that there is evidence to support the use of glutamate and PACAP as neurotransmitters in NIF photoperception by rat ipRGCs, and that these neurotransmitters are co-stored and probably released from the same nerve terminals. Furthermore, we conclude that VGLUT2 is the preferred subtype of vesicular transporter used by these cells.

Myosin heavy-chain isoform distribution, fibre-type composition and fibre size in skeletal muscle of patients on haemodialysis

Objective. Chronic uraemia is associated with abnormalities in skeletal muscles, which can affect their working capacity. It is also well known that the fibre-type composition of skeletal muscles influences endurance, muscle strength and power. In this study we therefore determined the size and distribution of muscle fibres and the myosin heavy-chain (MHC) isoform composition in patients on haemodialysis (HD) in order to establish any differences with values for untrained control subjects. Material and methods. Muscle biopsies were obtained from the vastus lateralis muscle of 14 non-diabetic patients on HD. The size and distribution of muscle fibres were evaluated using adenosine triphosphate synthase (ATPase) histochemistry, whilst MHC isoform composition was determined in muscle homogenates using sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Values were compared to those for a group of age-, gender- and BMI-matched untrained control subjects. The aerobic work capacity of the patients was also determined. Results. The MHC composition for I, IIA and IIX isoforms was found to be 35.3%±18.2%, 35.9%±7.1% and 28.9%±15.6%, respectively, findings supported by the ATPase histochemically determined fibre-type composition of the vastus lateralis muscle. The mean fibre area of type 1 and 2 fibres was 3283±873 and 3594±1483 µm2, respectively. The MHC composition and the size of the type 1 fibres of the patients on HD were significantly different from those of the control subjects. Conclusions. The data demonstrate relatively fewer type 1 and consequently more type 2x fibres, with a corresponding change in MHC isoforms (MHC I and MHC IIX) in the skeletal muscle of patients on HD. Several patients on HD were found to have <15% type 1 (or relative percentage of MHC I) fibres. Such a low percentage of type 1 fibres is very rarely observed in normal untrained subjects. Chronic uraemia more severely affects the composition than the size of fibres.

The Microvascular Volume of the Achilles Tendon Is Increased in Patients With Tendinopathy at Rest and After a 1-Hour Treadmill Run

Background: Achilles tendinopathy (AT) is initiated asymptomatically and is therefore often discovered at a very late stage. Purpose: To elucidate whether the microvascular volume (MV) of the Achilles tendon is elevated in patients with AT compared with healthy controls during pre-exercise rest, after acute exercise, and 24 hours after exercise. Additionally, this study investigated the muscle activation pattern of the gastrocnemius muscle and the relative elasticity of the Achilles tendon during a 1-hour treadmill run in healthy patients and in patients with AT. Study Design: Controlled laboratory study. Methods: Real-time harmonic contrast-enhanced ultrasound (CEU) measurements of the MV of the Achilles tendon were taken in 18 volunteers (9 patients with AT, 9 healthy controls). The CEU analyses were conducted before exercise, immediately after a 1-hour treadmill run, and 24 hours after exercise. Surface electromyography (EMG) signals of the gastrocnemius were recorded continuously during the 1-hour treadmill run. Results: In both the controls and the patients with AT, the MV of the Achilles tendon was increased after exercise as compared with before exercise (P < .005). Additionally, the MV signal was significantly larger in the patients with AT before, immediately after, and 24 hours after the running exercise compared with values in healthy controls (P < .0001). The muscle activation pattern differed in patients with AT compared with controls in that controls had increased EMG amplitudes at the end of the 1-hour treadmill run in the medial and lateral gastrocnemius (P < .0001). Moreover, patients with AT had approximately 15% less elastic Achilles tendons at the beginning of the 1-hour treadmill run, a condition that did not change because of exercise. Conclusion: Acute exercise increases the MV of the Achilles tendon in healthy patients and patients with AT in a similar manner. However, patients with AT have a significantly larger MV at all time points compared with healthy patients, supporting the hypothesis that microvascular changes may be involved in the pathogenesis of tendinopathy. Clinical Relevance: This study underlines that tendon flexibility is altered in patients with AT and that CEU is a promising tool to establish the early diagnosis of this condition.

The acute effects of exercise on the microvascular volume of Achilles tendons in healthy young subjects.

Real‐time harmonic contrast‐enhanced ultrasound (CEU) is used in several diseases to visualize the microvascularization in various tissues, due to its high sensitivity.

Altered pupillary light reflex in PACAP receptor 1-deficient mice.

The pupillary light reflex (PLR) is regulated by the classical photoreceptors, rods and cones, and by intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin. IpRGCs receive input from rods and cones and project to the olivary pretectal nucleus (OPN), which is the primary visual center involved in PLR. Mice lacking either the classical photoreceptors or melanopsin exhibit some changes in PLR, whereas the reflex is completely lost in mice deficient of all three photoreceptors. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is co-stored with melanopsin in ipRGCs and mediates light signaling to the brain via the specific PACAP receptor 1 (PAC1R). Here, we examined the occurrence of PACAP and PAC1R in the mouse OPN, and studied if lack of PAC1R affected the PLR. PACAP-immunoreactive nerve fibers were shown in the mouse OPN, and by in situ hybridization histochemistry, we demonstrated the presence of PAC1R mRNA. Mice lacking PAC1R exhibited a significantly attenuated PLR compared to wild type mice upon light stimulation, and the difference became more pronounced as light intensity was increased. Our findings accord well with observations of the PLR in the melanopsin-deficient mouse. We conclude that PACAP/PAC1R signaling is involved in the sustained phase of the PLR at high irradiances.

The uses and adverse effects of beryllium on health.

Context: This review describes the health effects of beryllium exposure in the workplace and the environment. Aim: To collate information on the consequences of occupational and environmental exposure to beryllium on physiological function and well being. Materials and Methods: The criteria used in the current review for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability, and Health. Articles were classified based on acute and chronic exposure and toxicity of beryllium. Results: The proportions of utilized and nonutilized articles were tabulated. Years 2001–10 gave the greatest match (45.9%) for methodological parameters, followed by 27.71% for 1991–2000. Years 1971–80 and 1981–90 were not significantly different in the information published and available whereas years 1951–1960 showed a lack of suitable articles. Some articles were published in sources unobtainable through requests at the British Library, and some had no impact factor and were excluded. Conclusion: Beryllium has some useful but undoubtedly harmful effects on health and well-being. Measures need to be taken to prevent hazardous exposure to this element, making its biological monitoring in the workplace essential.

The long‐term effect of α‐ketoglutarate, given early in postnatal life, on both growth and various bone parameters in pigs

The long-term effect of alpha-ketoglutarate (AKG) given for 21-24 days post-partum, on the skeleton of commercial pigs, was investigated. In experiment A, 12 pigs were given AKG [0.1 g/kg of body weight (b.w.) per day per os], while 12 controls were administered vehicle. At day 169, the left and right femur, humerus and sixth ribs were analysed for mechanical and geometrical properties and quantitative computed tomography. In experiment B, 32 piglets were divided equally into an AKG group (0.3 g/kg of b.w. per day) or a control group. Blood, taken at days 24 and 53 was analysed for plasma 17 beta-oestradiol. The main bone effect of AKG was to increase bone length in the sixth rib (7.3%, p < 0.01), ultimate strength (23%, p < 0.05), Young s modulus (52%, p < 0.001) and maximum elastic strength (31%, p = 0.056) compared with controls. In both experiments, AKG preferentially increased the growth of female piglets, whilst for male piglets AKG had the opposite effect. In addition, AKG elevated plasma 17 beta-oestradiol levels compared to those of controls at the end of the period of treatment (20%, p = 0.002). It is concluded that AKG has long-term effects on rib properties when given early in postnatal life whilst it elevates plasma 17 beta-oestradiol levels only so long as it is being administered.

Vitamin D, Surface Electromyography and Physical Function in Uraemic Patients

Background: Muscle function is impaired in uraemic patients and several causes have been proposed. Deficiency of 25-hydroxyvitamin D (25-OHD), which affects muscle function in non-uraemic patients, may very well also be associated with the myopathy found in these patients. The aim of this study was to investigate the association between 25-OHD and muscle function as well as physical function in chronic kidney disease (CKD) and peritoneal dialysis (PD) patients. Methods: In this cross-sectional study, 21 adult patients with CKD stage 3–5 and 21 patients treated with PD were included. Standard biochemistry parameters were measured including 25-OHD, 1,25-dihydroxycholecalciferol (1,25-OHD) and parathyroid hormone analysis. Muscle function was determined by 30-second surface electromyography (sEMG) recordings of a right thigh muscle (vastus lateralis) and a second left finger muscle (second dorsal interosseous) under voluntary contractions. Physical function was determined using a 30-second Chair Stand Test and the Short Form 36 quality of life questionnaire. Clinical characteristics were collected from the patient records. Results: Moderate vitamin 25-OHD deficiency (<40 nmol/l) was measured in 52% of patients with CKD and in 71% of the patients on PD. Severe deficiency (<15 nmol/l) was measured in 14% of patients on PD. There were no significant differences between the CKD and PD patients in terms of sEMG results. 25-OHD was not correlated to any results from the tests of sEMG or physical function. However, a higher sEMG frequency and signal root mean square (RMS) were positively associated with a higher Chair Stand Test score. Time to maximum sEMG frequency was negatively correlated to the Chair Stand Test score (p < 0.05), and positively correlated to the level of comorbidity (p < 0.05). sEMG signal peak-peak amplitude, frequency and RMS were positively correlated to the quality of life scales Physical Function, Role Physical, General Health, Vitality, Social Function, Mental Health, and Physical Component Scale (p < 0.001). Conclusions: 25-OHD deficiency was prevalent in uraemic patients in the present study. Muscle function as determined using sEMG and the Chair Stand Test was not associated with 25-OHD. The results may be biased by the limited variation in 25-OHD and masked by effects of several other variables in this very sick population.

An Ancient Greek Pain Remedy for Athletes

Abstract:  While Hippocratic writings make no reference to the actual Olympics, there is frequent mention of diet, exercise, and the treatment of injuries sustained by the athletic participants. Indeed, Galen in his Composition of Medicines gives details of a remedy prescribed for the relief of pains and swellings, which was reserved for use by the winners of Olympic events, the so‐called “Fuscum Olympionico inscriptum”—(ointment) entitled “dark Olympic victor’s.” In a time when the Olympic games have recently returned to their homeland, we examine the potential efficacy of this ancient remedy in terms of pain relief, the novelty of transdermal pain management, and the ability of ancient physicians to attend to the sports‐related needs of highly tuned athletes.