Calcium relieves fluoride-induced bone damage through the PI3K/AKT pathway.

Bone is the main target of fluorosis, and it has been perfectly elaborated that a moderate dosage of calcium (Ca) can alleviate bone fluorosis. However, whether Ca can alleviate fluorosis through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway has not yet been reported. Hence, we evaluated the histopathological structure, the imbalance of the biochemical index of bone metabolism, and the expression levels of PI3K/AKT apoptosis signaling pathway-related genes in rats treated with sodium fluoride (NaF, F) and/or calcium carbonate (CaCO3) for 120 days. Our results suggest that 100 mg L-1 NaF induced histopathological injury as alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (StrACP) activity increased, with a decrease in the serum Ca levels (p < 0.05). Moreover, the results of qRT-PCR and western blotting showed that F increased the expression levels of transglutaminase 2 (TGM2), focal adhesion kinase (FAK), PI3K, AKT, forkhead box O1 (Foxo1), Bcl-2 interacting mediator of cell death (BIM), Bcl2-associated x protein (Bax) and Caspase 3 (p < 0.05, p < 0.01). It also decreased the expression of AnnexinA5 (Anxa5), 3'-phosphoinositide-dependent kinase 1 (PDK1) and B-cell lymphoma-2 (Bcl-2) (p < 0.05, p < 0.01), which finally activated the PI3K/AKT pathway. On the other hand, CaCO3 supplementation reversed the histopathological injury along with the levels of ALP, StrACP and serum Ca, alleviating the gene expression levels of PI3K/AKT pathway-related markers. Altogether, we can conclude that CaCO3 supplementation mitigated F-induced bone damage via the PI3K/AKT signaling pathway.

Management of a Rare Case With Severe Hydrofluoric Acid Burns: Important Roles of Neutralizers and Continuous Renal Replacement Therapy.

Hydrofluoric acid (HF), a dangerous inorganic acid, is widely used in various industries and in daily life. Chemical burns caused by HF exposure occur more frequently in some regions worldwide. It has been reported that some cases with HF burns can be lethal due to the hypertoxicity of HF. In this article, we present a case of a 24-year-old worker who suffered HF burns by 53% HF solution to his face, neck, and nasal cavity. This patient quickly developed electrolyte disturbance, that is, hypocalcemia, and hypopotassemia, and myocardial injury after exposure. Multiple measures had been taken to treat this patient, including fluid resuscitation, electrolyte replacement, timely wound treatment with neutralizers, and respiratory tract care. Moreover, continuous renal replacement therapy was also employed to remove fluoride in the circulatory system and rectify the electrolyte disturbance and acid-base imbalance. The patient smoothly pulled though and survived. High fluoride levels in the dialysate solution were confirmed, indicating that continuous renal replacement therapy is an effective and potentially lifesaving treatment for acute HF poisoning.

[Dermal and inhalation poisoning. Rare guests in our intensive care units?]. / Dermale und inhalative Intoxikationen. Seltene Gäste auf unseren Intensivstationen?

Patients with dermal and inhalation poisoning are uncommon in intensive care treatment. We describe the diagnostics and specific toxicological treatment of patients with hydrofluoric acid burns. For inhalation poisoning, we focus on smoke inhalation, especially the management of cyanide and carbon monoxide poisoning. Special attention is given to the use of hyperbaric oxygenation for the treatment of carbon monoxide poisoning.

Combined impact of exercise and temperature in learning and memory performance of fluoride toxicated rats.

In previous studies, we investigated a link between high fluoride exposure and functional IQ deficits in rats. This study is an extension conducted to explore the combined influence of physical exercise and temperature stress on the learning ability and memory in rats and to assess whether any positive modulation could be attenuated due to exercise regimen subjected to F-toxicated animals at different temperatures. Accumulation of ingested fluoride resulted significant inhibition in acetylcholinesterase activity (P < 0.05), plasma cortisol levels (P < 0.05), and impaired the acquisition, performance, latency time, and retention in fluoride-exposed animals. Fluoride-toxicated rats took more number of sessions during the learning phase [F (5, 35) = 19.065; P < 0.05] and post hoc analysis on the number of correct choices revealed that there was a significant effect of treatments [F (5, 30) = 15.763; P < 0.05]; sessions [F (8, 240) = 58.698; P < 0.05]; and also significant difference in the interactions [F (40, 240) = 1.583; P < 0.05]. The latency data also revealed a significant difference between groups [F (5, 30) = 28.085; P < 0.05]; time = [F (8, 240) = 136.314; P < 0.05]; and there was a significant difference in the interactions [F (40, 240) = 2.090; P < 0.05]. In order to ascertain if interdependence between fluoride concentrations and the foregoing free radical parameters, respective correlation coefficients were calculated and results clearly emphasize the positive role of exercise in the promotion of cognitive functions by decreasing fluoride levels in rat hippocampus. A significant recovery in cognitive function was noticed in all the exercised animals due to reduced burden of brain oxidative stress. In comparison to exercise regimens performed at different temperatures, high (35 °C) and low temperatures (20 °C) led to a slower acquisition and poor retention of the task when compared to thermo neutral temperatures (25 and 30 °C). Thus exercise up-regulate antioxidant defenses and promote learning abilities in fluorotic population.

Use of hemodialysis after ingestion of a mixture of acids containing hydrofluoric acid.

Hydrofluoric acid (HF) is a highly toxic poison that can be rapidly fatal. Death usually results from the many systemic effects of dissociated fluoride ions, including hypocalcemia, hypomagnesemia, hyperkalemia, and direct cardiotoxicity. A patient is described who accidentally ingested a hydrofluoric acid-containing substance and who likely benefited from hemodialysis. His fluoride level post-dialysis was reduced by approximately 70% from a level drawn three hours prior to the initiation of hemodialysis. However, the single treatment did not reduce the fluoride level to normal. A review of the pathophysiology of hydrofluoric acid intoxication and the outcomes of prior exposures suggests that hemodialysis could play a vital role in the management of poisonings with fluoride-containing substances. However, the initial hemodialysis treatment should be prolonged beyond the standard four-hour session.

The tissue distribution of fluoride in a fatal case of self-poisoning.

The purpose of this paper is to report a case of fluoride poisoning along with a discussion of poisoning characteristics, analytical procedures, and a review of previous reports of fatal intoxications with analytical data. A case of suicidal ingestion of 40 mL of a rust removal agent containing hydrofluoric acid and ammonium fluoride by a 33-year-old white male is presented. He had an organic personality disorder with residual schizophrenia and previous suicide attempts with therapeutic drugs and cleaning products. At admission, he presented with a Glasgow coma score of 3, third degree atrioventricular block, and asystole. Resuscitation efforts were performed during which the patient suffered two episodes of ventricular fibrillation followed by asystole. In spite of advanced resuscitation efforts and the administration of calcium chloride, he died 2.5 h after the ingestion. Analytical data in the hospital showed calcium levels of 3.1 mg/dL and metabolic acidosis. Internal findings were erosive gastritis, brain edema, and pulmonary and hepatic congestion. Quantitation of fluoride was performed using an ion-selective electrode for the anion. Disposition of fluoride in the different tissues was as follows: peripheral blood, 19.4 mg/L; urine, 670 mg/L; vitreous humor, 2.5 mg/L; liver, 40.0 mg/kg; kidney, 60.0 mg/kg; lung, 17.5 mg/kg; brain, 2.5 mg/kg; spleen, 30.0 mg/kg; bone, 0.5 mg/ kg; and gastric content, 1120 mg/L (67 mg total). Validation of the analytical method was performed using different spiked tissues, in a range of concentrations from 2.4 to 475 mg/L or mg/kg, and submitting them to dilution (1:25) to avoid the matrix effect and to bring these concentrations to the range of the aqueous calibration curve (0.19-19 mg/L). Limits of detection and quantitation were 0.02 and 0.1 mg/L, respectively. The linearity of the method, for all studies tissues, was excellent, with r(2) values of 0.999. Accuracy and precision were within 10.5% and 5.7%, respectively. Fluoride analyses using the ion selective electrode are simple, sensitive, and rapid. This report provides an extensive tissue distribution study of fluoride after a well documented case of acute poisoning. Based on the autopsy findings, patient history, toxicology results, and previously reported data the forensic pathologists ruled that the cause of death was due to a fluoride poisoning, and the manner of death was listed as suicide.

Hydrofluoric acid-induced burns and life-threatening systemic poisoning--favorable outcome after hemodialysis.

BACKGROUND: Skin contact with hydrofluoric acid (HF) may cause serious burns and life-threatening systemic poisoning. The use of hemodialysis in fluoride intoxication after severe dermal exposure to HF has been recommended but not reported. CASE REPORT: A 46-year-old previously healthy man had 7% of his body surface exposed to 71% HE Despite prompt management, with subsequent normalization of the serum electrolytes, recurrent ventricular fibrillation occurred. On clinical suspicion of fluoride-induced cardiotoxicity, acute hemodialysis was performed. The circulatory status stabilized and the patient fully recovered. High fluoride levels in the urine and serum were confirmed by the laboratory. DISCUSSION: There is no ultimate proof that the favorable outcome in this case was significantly attributable to the dialysis. However, most reported exposures of this magnitude have resulted in fatal poisoning. As our patient had normal serum electrolytes and no hypoxia or acidosis at the time of his arrhythmias, it was decided that all efforts should be focused on removing fluoride from his blood. The rationale for performing hemodialysis for this purpose is clear, even though such intervention is more obviously indicated in patients with renal failure. CONCLUSION: Hemodialysis may be an effective and potentially lifesaving additional treatment for severe exposure to HF when standard management has proven insufficient.

[Metabolic effect of amaranth oil and impulse hypoxic training under chronic fluoride intoxication and small doses of ionizing radiation]. / Metabolichni efekty oliï amarantu ta impul'snoho hipoksychnoho trenuvannia za umov diï ftorystoï intoksykatsiï ta malykh doz radiatsiï.

Lipid peroxidation and antioxidative defence system in blood, liver and heart tissues, nitric oxide metabolites content in brain tissue of rats under binary action of small-doses of ionizing radiation and fluoride intoxication treated by amaranth oil and interval hypoxic training have been studied. Complex using of amaranth oil and interval hypoxic training result in increase both enzymatic, as nonezymatic links of antioxidant defence in all investigated tissues. It was revealed also enhance of NO system metabolites content in brain gomogenate. In this conditions lipid peroxidation processes in liver and heart tissues normalize comparison with essential increase level LPO under binary action influence. On the basis of obtained results LPO metabolites content we can suppossed that complex using of amaranth oil and interval hypoxic training result in increase of organism adaptative possibility. This complex can be using for binary action of ionizing radiation and fluoride intoxication correction.

Acute fluoride ingestion: recognition and management.

Occasionally, the Oral Health Division of the Indiana State Department of Health receives inquiries regarding diagnosis and treatment of acute fluoride ingestion. Because a wide variety of fluoride preparations are available in the dental setting and over the counter, excessive ingestion of fluoride can occur if these products are not used properly. The following article is meant to be a quick and easy guide in the recognition and management of instances of acute fluoride ingestion.

[Changes in energy metabolism parameters of the liver in acute fluoride intoxication and hyperbaric oxygenation]. / Zmina pokaznykiv energetychnogo metabolizmu v pechintsi pry gostrii intoksykatsii ftorydom natriiu i zastosuvanni giperbarychnoi oksygenatsii.

Examinations of energetic metabolism in liver of white rats with acute fluoride intoxication were carried out in acute and recovering periods. The influence of hyperbaric oxygenation on the change of energetic metabolism indices and on survival rates of animals has been studied. Hyperbaric oxygenation greatly prevented profound metabolic disturbances, in particular, ATP, increased detoxic in liver intensifying energetic forming processes. The survival rate of animals under the influence of course of HBO increased by 27% during first 72 hours. It was determined that HBO has an effective influence on the course of recovering period during fluoride intoxication.

[Changes of energy metabolism and concentration of cyclic nucleotides in the kidneys in acute fluoride intoxication and hyperbaric oxygenation]. / Zminy energetychnogo metabolizmy i kontsentratsii tsyklichnykh nukleotydiv u nyrkakh pry gostrii ftorystii intoksykatsii i zastosyvanni giperbarychnoi oksygenatsii.

The energy metabolism and indices of the adenylate-cyclase system in kidneys of rats with acute fluoric intoxication have been studied. It has been determined that the use of hyperbaric oxygenation prevents deep disturbances of energy metabolism in the renal tissue and restricts the increase of adenosine monophosphate concentration. Moreover the survival rate of animals has increased by 30% for the first 24 hours.

Toxicologia do flúor / Fluoride toxicology

O autor apresenta o processo toxicológico em relaçäo ao fluoreto, classificando-o e cita dados que marcam os possíveis limites de intoxicaçäo crônica e aguda, bem como refere os tipos de tratamento e cuidados para cada caso

[The treatment of occupational fluorosis by acupuncture reflexotherapy]. / Lechenie professional'nogo fliuoroza iglorefleksoterapiei.

The article contains the electrodiagnostic data on 26 auricular points in 24 fluorosis-affected patients. It was established that the greatest electrical polarity asymmetry was found in points 13, 25, 28, 31, 54, 37, 39 and 40. Palpation of the auricular and corporal points also showed unfavorable conditions in the respective painful point of the organ. Basing on the results of the acupuncture procedures, needle therapies of 80 occupational fluorosis cases were performed. The therapeutic patterns elaborated by the author were also proposed, which proved perfect results at different stages of the disease.

Acute fluoride toxicity. Pathophysiology and management.

Acute intoxication with inorganic fluoride disrupts numerous physiological systems. As a potent acid it acts corrosively on the skin and mucous membranes, producing severe burns. As the most electronegative element it tightly binds many cations essential to homeostasis, producing, for example, profound hypocalcaemia and resultant inhibition of normal blood coagulation. As a metabolic poison it stimulates some enzymes, such as adenylate cyclase, and severely inhibits others, such as Na(+)-K(+)-ATPase and the enzymes of carbohydrate metabolism. Death can result from these processes and also from a delayed, explosive hyperkalaemia. Therapy of acute poisoning is aimed first, at preventing the absorption of fluoride by incorporating it into insoluble fluoride compounds; secondly, at enhancing fluoride tolerance by maintaining normal blood pH and electrolytes, and aggressive general support of the toxic patient; and thirdly, at manipulating renal excretion or removing fluoride with dialysis and haemoperfusion. If the poisoned patient can be supported for 24 hours, the prognosis improves markedly, although delayed toxicity can occur.

[Therapeutic effect of low-fluorine drinking water on fluorosis of bone].

495 clinical cases and 25 radiographic cases of fluorosis of bone diagnosed six years ago in an endemic area showed satisfactory results after six years' treatment with low-fluorine drinking water. Among these, 140 have been completely cured, 105 have gained marked clinical improvement and 172 have gained moderate improvement; the cure rate being 49.49% and the effective rate, 84.84%. Of the 25 X-ray diagnosed cases, 15 showed marked improvement. Radiographic examination has revealed reappearance of evenly distributed fine bone trabeculae. Two cases of grade III osteosclerosis have turned to grade II; 4 to grade I; 8 cases of grade II have turned to grade I; 1 case of grade I has become normal. The results demonstrate that fluorosis of bone is reversible.