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Circulating levels of immunoreactive parathyroid hormone in endemic genu valgum.

Circulating levels of immunoreactive parathyroid hormone (PTH) were estimated in fifteen normal subjects and twenty-five subjects suffering from the skeletal fluorosis, ten of whom had associated endemic genu valgum. Levels of PTH were high in all the subjects with fluorosis as compared to normals, but among fluorosis subjects, those who had endemic genu valgum had values strikingly higher than those without. It is suggested that secondary hyperparathyroidism may have a significant role to play in the pathogenesis of osteoporosis seen in patients with endemic genu valgum.

Adolescent↗

Bone and joint pathology in fluoride-exposed workers.

Clinical and radiological investigations were performed for 2,258 aluminum workers exposed to fluoride for an average of 17.6 yr (standard deviation = 7.6). Changes in bone and joints were presented in detail in three groups: (1) exposed up to 5 yr (135 cases), (2) exposed from 6-32 yr (1,463 cases), and (3) retired workers (660 cases). A semiquantitative assessment of early fluorosis was introduced. A 20.2% incidence of fluorosis was found, but, according to Roholm, only 1.05% was in stage I. The disease was mainly in the pre-stages of O and OI. A close relationship between the occurrence of fluorosis and the time and degree of fluoride exposure was found. The difficulties in diagnosing skeletal fluorosis result from the questionable sensitivity of the x-ray techniques and from the nonspecificity of the associated symptoms. A quantitative method to assess osteosclerosis and bone structure alteration is needed.

Adolescent↗

Evaluating a fluorosis hazard after a volcanic eruption.

The August, 1991 eruption of Mt. Hudson (Chile) deposited ash across southern Argentina and contributed to the deaths of thousands of grazing sheep. Early ash analysis revealed high levels of fluoride, a potential ash constituent toxic to humans and animals. In order to evaluate fluorosis as the cause of sheep deaths and to examine the possibility that similar ash and airborne toxins could also have an effect on the human population, we conducted an investigation that included health provider interviews, hospital record review, physical examination of sheep, determination of sheep urine fluoride levels, and complete constituent analysis of ash samples collected at proscribed distances from the volcano. Ash deposited farthest from the volcano had highest fluoride levels; all fluoride measurements were normal after rainfall. There were no signs or symptoms of fluorosis observed in sheep or humans. Sheep deaths resulted from physical, rather than chemical properties of the ash.

Animals↗

Effect of helium on the respiration and glycolysis of mouse liver slices.

It has been shown that helium has the ability to affect variously the rates of certain metabolic reactions in vitro as compared to nitrogen. An attempt has been made to approximate the sites of action in mouse liver preparations. The following results have been obtained by the substitution of a mixture of 80 per cent helium and 20 per cent oxygen for air: (a) An increase in the rate of oxygen consumption and carbon dioxide production to the same degree, the respiratory quotient remaining unchanged. (b) A decrease in the magnitude of cyanide inhibition. The effectiveness of helium increases with the degree of the cyanide inhibition. (c) No effect on the activity of slices which have been poisoned with fluoride when either lactate or pyruvate has been added as a substrate. (d) A change in the rate, and the slope of the curve of oxygen consumption in liver homogenates which are utilizing pyruvate as a substrate. The use of helium relative to nitrogen under anaerobic conditions causes: (a) A depression of the glycolytic rates in both mouse liver slices and diaphragm. (b) An increase in the carbon dioxide evolution and lactic acid production of mouse liver homogenates oxidizing either glucose and hexose diphosphate, or hexose diphosphate alone. In neither slices nor homogenates does the addition of fluoride and the use of pyruvate as the hydrogen acceptor alter the fundamental response of the preparations. The following hypotheses have been advanced and discussed in order to explain the observed phenomena: 1. Helium does not alter the substrate utilized by the tissue. 2. The gas interferes in some way with the cyanide-cytochrome oxidase bond, but may not affect cytochrome oxidase in the absence of cyanide. 3. The citric acid cycle is not subject to the influence of helium in tissue slices, but is altered in an unexplained fashion in homogenates. It is postulated that a rearrangement of particulate surfaces may be the significant factor here. 4. The glycolytic cycle is the site of both an inhibitory and an acceleratory effect of helium. The locus of the inhibition lies above the aldolase reaction and that of the acceleration between the aldolase and enolase reactions.

Animals↗

Cross-sectional study of health effects of cryolite production.

A cross-sectional health study of 101 cryolite workers was performed, using spirometry and a questionnaire. Multiple regression analysis revealed a significant correlation between the index of smoking and a decrease in FEV1 (per cent). There was no significant correlation between work-related exposure and lung function. Many cryolite workers described a group of symptoms appearing after 15 to 30 min of heavy dust exposure: nausea, followed by epigastric pain with relief after spontaneous or provoked vomiting. Thirty-four (33.6 per cent) workers complained of nausea, vomiting or diarrhoea in relation to work, compared to 3.8 per cent of 1752 men participating in the Copenhagen Male Study.

Adult↗

Antioxidant defense system and lipid peroxidation in patients with skeletal fluorosis and in fluoride-intoxicated rabbits.

Fluorosis is a serious public health problem in many parts of the world where drinking water contains more than 1 ppm of fluoride. The main manifestations of skeletal fluorosis are crippling bone deformities, spinal compressions, and restricted movements of joints. Although fluorosis is irreversible, it could be prevented by appropriate and timely intervention through understanding the process at biochemical and molecular levels. As in the case of many chronic degenerative diseases, increased production of reactive oxygen species (ROS) and lipid peroxidation has been considered to play an important role, even in the pathogenesis of chronic fluoride toxicity. However, there is inconclusive proof for an altered oxidative stress and antioxidant balance in fluorosis, and the existing data are not only conflicting but also contradictory. In the present communication we have evaluated the antioxidant defense system (both enzymatic and nonenzymatic) and lipid peroxidation in both humans from an endemic fluorosis area (5 ppm fluoride in the drinking water) and in rabbits receiving water with 150 ppm of fluoride for six months. There was no significant difference in lipid peroxidation, glutathione, and vitamin C in the blood of human fluorotic patients and fluoride-intoxicated rabbits as compared to respective controls. Neither were there any changes in the activities of catalase, superoxide dismutase, glutathione peroxidase, or glutathione S-transferase in the blood due to fluoride intoxication (of rabbits) or fluorosis in humans. The results together do not subscribe to oxidative stress theory in fluorosis. Thus, in the absence of clear proof of oxidative damage and to counter toxic effects of fluoride through supplementation of antioxidants, extensive investigations are needed to conclusively prove the role of oxidative stress in skeletal fluorosis.

Adult↗

Skeletal scintigraphic findings in endemic skeletal fluorosis.

Endemic skeletal fluorosis is characterized by bone, joint and muscle pain, progressive ankylosis of various joints and crippling deformities. Whole body skeletal scintigraphy with 99Tcm-methylene diphosphonate was performed for 17 symptomatic subjects suffering from this disorder. The fluoride content of drinking water ranged from 4.1 to 12.9 mg l-1 (normal < 1 mg l-1). Urinary and serum fluoride levels were markedly elevated. Serum calcium (total and ionized), inorganic phosphorus, creatinine and albumin were essentially normal while serum alkaline phosphatase was elevated in six subjects (mean +/- S.D. 206 +/- 106; range 22-1072 IU l-1). Skeletal radiology revealed a wide spectrum of bony abnormalities. Skeletal scintigraphy revealed a picture similar to metabolic 'superscan' in all subjects, i.e. increased tracer uptake in axial and appendicular skeleton, reduced soft tissue uptake, poor or absent renal images, prominent costochondral junction and 'tie' sign in sternum. Increased uptake was present in all subjects irrespective of age, water fluoride content, serum alkaline phosphatase level and radiological abnormalities. Our findings suggest the presence of a high bone turnover state in endemic skeletal fluorosis irrespective of other variables.

Adolescent↗

Diffuse idiopathic skeletal hyperostosis: Forestier's disease.

Diffuse idiopathic skeletal hyperostosis (DISH) or Forestier's disease is characterized by calcification and ossification of soft tissue entheses of ligaments and tendons. DISH is believed to be a variant of osteoarthritis (OA) without the degenerative intervertebral disc and joint degenerative qualities seen in classic OA. The likely pathoetiologic causes of DISH are presented.

Comorbidity↗