Effect of pesticides on phosphorylation of tau protein,and its influence on Alzheimer’s disease

Alzheimer’s disease(AD)is a progressive and neurodegenerative illness which results in alterations in cognitive development.It is characterized by loss/dysfunction of cholinergic neurons,and formation of amyloid plaques,and formation of neurofibrillary tangles,among other changes,due to hyperphosphorylation of tau-protein.Exposure to pesticides in humans occurs frequently due to contact with contaminated food,water,or particles.Organochlorines,organophosphates,carbamates,pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment.The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein,and its cognitive implications in the development of AD.It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198,Ser199,Ser202,Thr205,Ser396 and Ser404.Contact with these chemicals altered the enzymatic activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta,and protein phosphatase-2A.Moreover,it altered the expression of the microtubule associated protein tau gene,and changed levels of intracellular calcium.These changes affected tau protein phosphorylation and neuroinflammation,and also increased oxidative stress.In addition,the exposed subjects had poor level of performance in tests that involved evaluation of novelty,as test on verbal,non-verbal,spatial memory,attention,and problem-solving skills.

Unusual clinical presentation of oral pyogenic granuloma with severe alveolar bone loss:A case report and review of literature

BACKGROUND Pyogenic granuloma(PG)is a localized,reddish and vascularized hyperplastic lesion of the connective tissue which occurs in the oral cavity.In most cases,the presence of this lesion does not show alveolar bone resorption.The pathology is diagnosed clinically with some caution.However,the diagnosis and treatment are usually corroborated with histopathological evidence.CASE SUMMARY Three clinical cases of PG associated with bone loss were described in this study.The three patients presented tumor-like growth which bled on touch,and were associated with local irritant factors.Radiographs showed bone loss.All cases were treated with conservative surgical excision.The scarring was satisfactory,and there was no case of recurrence.The diagnoses were based on clinical findings,and were confirmed histopathologically.CONCLUSION The occurrence of oral PG with bone loss is unusual.Therefore,clinical and radiographic evaluations are important for the diagnosis.

Microsurgical management of radicular cyst using guided tissue regeneration technique:A case report

BACKGROUND Radicular cyst is a lesion of odontogenic origin that arises from epithelial remains due to periapical periodontitis caused by inflammatory reactions generated at the apex of affected teeth with infected or necrotic pulps.The therapeutic mana gement of radicular cysts is controversial.There is only one case report of enucleation of a radicular cyst managed with microsurgery and apicoectomy,but without the use of the guided tissue regeneration(GTR)technique in the same surgical procedure.The present clinical case describes the management of a radicular cyst with microsurgical approach,performance of an apicoectomy of the tooth associated with the entity,application of GTR technique,use of a resorbable membrane of type I bovine collagen,and bovine xenograft.CASE SUMMARY A 68-year-old patient presented with a radicular cyst from an upper lateral incisor.The microsurgical management used was aimed at enucleating the chemical membrane,performing apicoectomy of the tooth along with careful and precise retrograde filling,and implementing GTR technique using a resorbable collagen membrane and bovine xenograft.The diagnosis of radicular cyst was confirmed using histopathological analysis.The patient underwent follow-up evaluations at 10 and 30 d postoperatively.At 4 months postoperative evaluation,she remained asymptomatic,and radiographs showed significant periapical healing with adequate bone formation.CONCLUSION These results suggest that microsurgical management using the GTR technique with collagen membrane and xenograft,contributes to bone regeneration.

Effect of structure and function of paraoxonase-1(PON-1)on organophosphate pesticides metabolism

Paraoxonase-1(PON1)is an important enzyme in various pathologies such as pesticide poisoning,diabetes,atherosclerosis,neuronal disorders,and cancer,due to its multifunctional activity since it acts on different metabolites.However,one of its main functions is the hydrolysis of organophosphate(OP)compounds from pesticides that cause fatal poisoning at the level of the central nervous system(CNS).The objective of this review was to investigate whether the structure,genetics,and function of PON1 affect the metabolism of organophosphate pesticides or other abnormalities.Information was selected from articles in the database PubMed–NCBI(https://www.ncbi.nlm.nih.gov/pubmed/)with a publication date between 2011 and 2019.The enzymatic activity of PON1 can be modified depending on its chemical structure since there are different genetic polymorphisms that change PONI morphologies or the levels of expression in the bloodstream.This leads to differences in susceptibilities to organophosphate pesticide poisoning.The results of this review reveal that phenotypic variants of PON1 have differences in affinities for OP substrates.

Cognitive disorder and dementia in type 2 diabetes mellitus

Insulin,a key pleiotropic hormone,regulates metabolism through several signaling pathways in target tissues including skeletal muscle,liver,and brain.In the brain,insulin modulates learning and memory,and impaired insulin signaling is associated with metabolic dysregulation and neurodegenerative diseases.At the receptor level,in aging and Alzheimer’s disease(AD)models,the amount of insulin receptors and their functions are decreased.Clinical and animal model studies suggest that memory improvements are due to changes in insulin levels.Furthermore,diabetes mellitus(DM)and insulin resistance are associated with age-related cognitive decline,increased levels ofβ-amyloid peptide,phosphorylation of tau protein;oxidative stress,pro-inflammatory cytokine production and dyslipidemia. Recent evidence shows that deleting brain insulin receptors leads to mildobesity and insulin resistance without influencing brain size and apoptosis development.Conversely, deleting insulin-like growth factor 1 receptor (IGF-1R) affects brain size anddevelopment, and contributes to behavior changes. Insulin is synthesized locally in the brain andis released from the neurons. Here, we reviewed proposed pathophysiological hypotheses toexplain increased risk of dementia in the presence of DM. Regardless of the exact sequence ofevents leading to neurodegeneration, there is strong evidence that mitochondrial dysfunctionplays a key role in AD and DM. A triple transgenic mouse model of AD showed mitochondrialdysfunction, oxidative stress, and loss of synaptic integrity. These alterations are comparable tothose induced in wild-type mice treated with sucrose, which is consistent with the proposal thatmitochondrial alterations are associated with DM and contribute to AD development. Alterationsin insulin/IGF-1 signaling in DM could lead to mitochondrial dysfunction and low antioxidantcapacity of the cell. Thus, insulin/IGF-1 signaling is important for increased neural processing andsystemic metabolism, and could be a specific target for therapeutic strategies to decreasealterations associated with age-related cognitive decline.

Relationship between PON-1 enzymatic activity and risk factors for pesticide poisoning in farmers from the Cienega,Jalisco,Mexico

Paraoxonase-1(PON-1)is an enzyme that hydrolyzes organophosphate pesticides.The presence of polymorphisms in PON-1(L55M and Q192R)decreases its enzyme activity and increases the risk of central nervous system(CNS)toxicity in occupationally exposed farmers,leading to chronic degenerative diseases and death.We studied 103 farmers in the region of Cienega Jalisco,Mexico,which were exposed mainly to organophosphate pesticides.We used serum and plasma samples to assay PON-1 activity and perform polymorphism analysis(L55M and Q192R)using qPCR and TaqMan probes,respectively.For both polymorphisms,there was high percentage of heterozygosity(55 LL=0.19,LM=0.75,MM=0.06;192 QQ=0.12,QR=0.72,RR=0.16),while the allelic frequencies were more balanced(L=0.56,M=0.44;Q=0.48,R=0.52).There were no significant differences in enzyme activity of L55M polymorphism genotypes(LL=179.27;LM=192.11;MM=122.11;QQ=135.74;QR=187.90;RR=209;p>0.05).But there was a slight decrease in enzyme activity for the Q192R polymorphism genotypes.The genotype and alcohol consumption associated with slight increases in enzyme activity.However,genotype and tobacco consumption did not have a significant effect on PON-1 activity(μU/mL)(p>0.05).Overall,alcohol and tobacco consumption affected PON-1 enzyme activity(μU/mL)up to 21.1%.The data obtained in this study reveal that PON-1 activity is affected by genetic variants such as Q192R and alcohol consumption.This may influence the susceptibility of populations to organophosphate poisoning.

Gingival enlargement induced by cyclosporine in Medullary aplasia:A case report

BACKGROUND Cyclosporine is an immunosuppressive agent used effectively for treatment of a rare haematological disorder known as medullary aplasia.This drug prevents several side effects,including gingival enlargement(GE)which compromises aesthetics,phonetics and chewing,and also predisposes patients to periodontitis.CASE SUMMARY This clinical case reports a 41-year-old woman who presented with cyclosporineinduced GE with underlying periodontitis and medullary aplasia.The management of the disease was approached through multidisciplinary strategy which allowed for accurate diagnosis and a strategic treatment based on the systemic condition and severity of oral pathology.The diagnosis was confirmed through histopathological analysis.The treatment was carried out in phases:Initial(oral hygiene motivation,mechanical supragingival plaque control,and non-surgical therapy);systemic treatment,corrective treatment,and maintenance.CONCLUSION Multidisciplinary management of cyclosporine-induced GE and medullary aplasia allows for correct diagnosis and effective treatment of this pathological expression through a phased therapeutic approach.