Novel Probable Glance at Inflammatory Scenario Development in Autistic Pathology

Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and restricted-repetitive patterns of behavior, interests, or activities. ASD is generally associated with chronic inflammatory states, which are linked to immune system dysfunction and/or hyperactivation. The latter might be considered as one of the factors damaging neuronal cells. Several cell types trigger and sustain such neuroinflammation. In this study, we traced different markers of immune system activation on both cellular (immune cell phenotypes) and mediatory levels (production of cytokines) alongside adverse hematology and biochemistry screening in a group of autistic children. In addition, we analyzed the main metabolic pathways potentially involved in ASD development: energy (citric acid cycle components), porphyrin, and neurotransmitter metabolism. Several ASD etiological factors, like heavy metal intoxication, and risk factors—genetic polymorphisms of the relevant neurotransmitters and vitamin D receptors—were also analyzed. Finally, broad linear regression analysis allowed us to elucidate the possible scenario that led to the development of chronic inflammation in ASD patients. Obtained data showed elevated levels of urinary cis-aconitate, isocitrate, alfa-ketoglutarate, and HMG. There were no changes in levels of metabolites of monoamine neurotransmitters, however, the liver-specific tryptophan kinurenine pathway metabolites showed increased levels of quinolinate (QUIN) and picolinate, whereas the level of kynurenate remained unchanged. Abovementioned data demonstrate the infringement in energy metabolism. We found elevated levels of lead in red blood cells, as well as altered porphyrin metabolism, which support the etiological role of heavy metal intoxication in ASD. Lead intoxication, the effect of which is intensified by a mutation of the VDR-Taq and MAO-A, leads to quinolinic acid increase, resulting in energy metabolism depletion and mitochondrial dysfunction. Moreover, our data backing the CD4+CD3+ T-cell dependence of mitochondrial dysfunction development in ASD patients reported in our previous study leads us to the conclusion that redox-immune cross-talk is considered a main functional cell damaging factor in ASD patients.

INFLUENCE OF HEAVY METALS ON ANTIOXIDANT SYSTEM AND BIOCHEMICAL INDEXES IN RATS

The study was undertaken to examine the effect of heavy metals on antioxidant system and biochemical indexes in the organism of rats. The influence of heavy metals on indexes The influence of heavy metals on the indicators of the antioxidant system (activity of the antioxidant system enzymes – glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase) and the processes of lipid peroxidation (content of hydroperoxides and products of thiobarbituric acid) was determined. It is established, that the antioxidant system functions more intensively in blood and liver of rats under the action of heavy metals. The study of enzyme activity showed the activation of the latter under conditions of heavy metal intoxication in 1.5–2.0 times (depending on heavy metal) compared with the control. We found that blood levels of total and direct bilirubin, creatinine, and urea increased in intoxicated rats from all experimental groups compared with intact animals. However, a decrease in the content of albumin, total protein, cholesterol, and triglycerides was also found in all experimental groups, in comparison with intact rats. Under the action of heavy metals, the activity of total α-amylase, lactate dehydrogenase, and glucose concentration increases in blood of rats. According to the results of studies in intoxicated animals compared with the intact group, there was a change in the cation-anion pool, in particular, a tendency to decrease the content of sodium and inorganic phosphorus and increase chlorides, magnesium, calcium, and potassium.

THE RESULTS OF STUDYING THE EFFICIENCY OF DIATOMITE AT INTOXICATION OF ANIMALS WITH CADMIUM AND LEAD

The combination of cadmium and lead in doses at the level of 10 MPC for feed caused in white rats a decrease in body weight and immunoglobulin content in blood serum, an increase in the summation threshold indicator, a decrease of the amount of protein in urine and SH-groups in blood serum, a significant increase in mass coefficients of the liver and kidneys. The use of diatomite as a means to reduce heavy metal intoxication slightly increased body weight. The use of means did not lead to normalization of the summation threshold indicator, did not significantly affect the content of SH-groups. In the group of animals treated with diatomite, the mass coefficients of the liver remained significantly higher than the control values. The obtained results indicate that diatomite did not show protective properties as a feed additive to reduce lead and cadmium intoxication.

Heavy Metal Intoxication: A Key-Player in Chronic Kidney Disease (A Review)

Heavy metals gain entry into biological systems mainly via inhalation and ingestion, and also via radiation or radio-therapeutic measures. The accumulation of these heavy metals in biological systems overtime may cause several deleterious health challenges such as liver, kidney and brain damages amongst others. Intoxication with heavy metals may either be acute or chronic, and because the kidney has the ability to reabsorb and accumulate divalent metals, it happens to be the primary target organ for heavy metal toxicity, inducing renal damage. The extent of this damage depends on the dose, nature, route and duration of exposure to the metal. Chronic kidney disease (CKD) is characterized by a permanent loss of nephrons accompanied by an eventual decline in glomerular filtration rate (GFR); this (to a greater extent) maybe due to heavy metal intoxication and the renal reabsorption of these heavy metals. Although 70 percent of the heavy metals are reabsorbed in the proximal tubule, all segments of the nephrons are involved in the reabsorption of these metals, where several transporters such as the Divalent Metal Transporter (DMT)-1, Na+/amino acid co-transporter, Zinc Transporter (ZnT)-1 and stretch-activated cation channels (SAC) facilitate the reabsorption. In the nephrons of each kidney, heavy metals are primarily reabsorbed via the apical membrane and accumulate at the basolateral membrane; these heavy metals do not readily exit the basolateral membrane, which overtime may result in chronic inflammation of the nephrons, fibrosis and kidney failure. However, the loss of nephrons and decline in GFR in CKD are compensated by certain changes (glomerular and cellular, enhanced renal blood flow, enhanced single nephron glomerular filtration rate and tubular hypertrophy) in the remaining functional nephrons. These changes help to deliver solutes to the remaining functional nephrons for uptake by the epithelial cells of the renal tubules. Also, because the luminal and basolateral surfaces of tubular epithelial cells of the remaining healthy nephrons are also potentially exposed to higher levels of metabolic wastes, xenobiotics, heavy metals and other nephrotoxicants, renal injury, tubular or glomerulosclerosis, and death of these nephrons occur. These compensatory changes become insufficient once about 75 percent of the nephrons are no longer functional and incapable of maintaining homeostasis and renal function. This results in the accumulation of metabolic wastes in the blood, and induction of metabolic disturbances and/or organ intoxication.

Chromium-Cobalt Intoxication with Intense Systemic Complications following Total Hip Revision after Per-Operative Ceramic Fracture

Introduction. Heavy metal intoxication after arthroplasty is extremely rare but could be lethal. Case Report. We report the case of a 69-year-old woman, who presented intense systemic symptoms of chromium-cobalt intoxication after revision of per-operative fractured ceramic components with metal-on-polyethylene. Systemic toxicity occurred a year after surgery and expressed brutally with mostly central neurological symptoms. Chelation associated with revision surgery allowed rapid regression of all symptoms. Conclusion. Revision of fractured ceramic, even per-operatively, should not be done with metal-on-polyethylene components, in order to avoid potentially lethal metal intoxication.

Heavy Metal Poisoning in a Cockatiel (Nymphicus hollandicus)

Background: In recent decades the demand for unconventional pets has been relatively increasing, a situation that increasingly causes veterinarians to encounter these animals in medical and surgical practice. Of these animals, the birds stand out. Animals of the order Psittaciform are known as very curious and active creatures that have the tendency to chew objectsin their environment. Among the several occurrences that lead this animal to attend the veterinary clinic, we highlight the poisoning by heavy metals, especially lead poisoning (Pb) and zinc (Zn). The objective of this work was to report a case of heavy metal intoxication in cockatiel (Nymphicus hollandicus).Case: A cockatiel was taken to the veterinarian with a history of apathy, motor incoordination, exacerbated water consumption and regurgitation. Complete anamnesis was instrumental in directing suspected heavy metal intoxication. Radiopaque particles were visualized through radiographic examination, suggesting heavy metal intoxication. The diagnosis wasconcluded through complementary examinations since the clinical symptoms are nonspecific. The treatment was intended to provide emergency intervention, avoid further absorption, use of antidotes, provide supportive measures and provide guidance to the owner. It can be concluded that the diagnosis and treatment were successful.Discussion: Metal poisoning can kill birds. The veterinarian should always seek the literature in order to perform the best support and treatment. For this, detailed history and detailed medical history must be taken into account, since the time of ingestion and the type of metal interfere with the therapeutic conduct. The use of imaging tests such as x-rays andultrasound are essential to assist the clinician, especially in cases where the tutor does not know whether or not the animal has ingested an object. In the radiographic examination, the heavy metal has the characteristic of having high radiopacity, which was evidenced in the case in question. Radiographic positions should be considered in order to avoid false negatives. In the literature, the treatment of chelation therapy is prioritized to remove the circulating heavy metal and thus act on the cause of the problem. In the case in question calcium EDTA was used intramuscularly, which showed clinical improvement in the animal after the second application. Calcium EDTA binds to metals and facilitates their transport and excretion. The use of fluid therapy is necessary as a supportive treatment to prevent kidney damage, since heavy metals are highlyharmful to nephrons. Especially in cases where the animal stops feeding and ingesting water. The use of antibiotics is essential because in many cases the animal, in addition to not feeding, becomes prone to infections due to metal toxicity, therefore, prophylactic use is essential for a better prognosis. In the case in question, the use of enrofloxacin was effective,as reported in the literature. It is recommended that the diagnosis of serum lead and zinc dosage should be made, however, due to the difficulties of obtaining the samples, and since other metals may also cause intoxication, in the case in question the treatment was started without these results. According to the results obtained in this work, the treatment described in the literature is effective and can be performed immediately to save animal life without subsequent sequelae.Keywords: bird, lead, zinc, calcium EDTA.

Heavy metal intoxication compromises the host cytokine response in Ascaris Suum model infection

SummaryLead (Pb), Cadmium (Cd) and Mercury (Hg) are recognized for their deleterious effect on the environment and immunity where subsequently compromised immune response affects the susceptibility to the potential parasitic infections. This study examined the host cytokine response after heavy metal intoxication (Pb, Cd, and Hg) and subsequent Ascaris suum infection in BALB/c mice. Pb modulated murine immune response towards the Th2 type of response (delineated by IL-5 and IL-10 cytokine production) what was also dominant for the outcome of A. suum infection. Chronic intoxication with Pb caused a more intensive development of the parasite infection. Cd stimulated the Th1 immune response what was associated with increase in IFN-γ production and reduction of larvae present in the liver of intoxicated mice. The larval burden was also low in mice intoxicated with Hg. This was probably not related to the biased Th1/Th2 type of immune response, but rather to the bad host conditions caused by mercury toxicity and high level of pro-cachectic cytokine TNF-α.