RESUMO
Rheumatoid arthritis (RA) was significantly associated with increased overall risk of periodontitis, both chronic, inflammatory pathologies leading to connective tissue breakdown and bone destruction. To identify clinical and/or serological variables routinely evaluated during follow-up of people with RA which are associated with the severity of their periodontal disease. An observational, cross-sectional study was carried out, which included RA patients according to ACR/EULAR 2010 criteria having chronic periodontal disease. RA clinical parameters (disease duration, erythrocyte sedimentation rate, serum C-reactive protein, disease activity (DAS28) and rheumatoid factor, presence of bone erosions and rheumatic nodules) and also corticosteroid therapy were considered. Periodontitis was evaluated according to the American Academy of Periodontology (1999) and chronic periodontitis was assessed by full mouth periapical radiographic examination, periodontal probing depth, clinical attachment level and bleeding index. A total of 110 subjects with RA and chronic periodontitis were included. The female/male relation was 5.1, and no significant differences between genres were found in rheumatic or oral variables. RA patients with longer disease duration, higher disease activity and with rheumatic nodules had significantly greater periodontitis severity. Multivariate analysis confirmed that severe periodontitis was associated with DAS283 4.1 (OR 51.4, CI 95% 9.4-281.5) and the presence of rheumatic nodules (OR 6.4, CI 95% 1.3-31.6). Disease activity and rheumatic nodules were strongly associated with severe periodontitis. Based on these findings it would be desirable to include interdisciplinary management at an early stage of RA to ensure comprehensive treatment of both pathologies.
Assuntos
Artrite Reumatoide , Periodontite Crônica , Nódulo Reumático , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Periodontite Crônica/complicações , Periodontite Crônica/terapia , Estudos Transversais , Feminino , Humanos , Masculino , Nódulo Reumático/complicações , Fator ReumatoideRESUMO
PURPOSE OF REVIEW: Presbyopia is the normal progressive loss of accommodation, which leads to the inability to focus clearly on objects located at different distances. Some of the accepted methods for treating this condition are glasses, contact lenses, and surgery. Pharmacological treatments are a new and promising noninvasive option for dealing with presbyopia. The aim of this review is to provide an update on some recent advances in this field. RECENT FINDINGS: Currently, there are three different strategies for the pharmacological treatment of presbyopia. The first one aims to produce miosis and increase depth of focus through a pinhole effect, therefore improving uncorrected near visual acuity. The second one tries to restore the elasticity the lens has lost due to aging. Finally, the third strategy is based on rehabilitating accommodation; which is to say, in a binocular way, allowing for good vision at all distances. SUMMARY: Pharmacological treatments are a new alternative that expands the diversity of existing strategies for treating presbyopia. These treatments are based on the instillation of eyedrops with different compositions, which vary according to the different strategies. Many of these developments will most likely be on the market in the next few years. If the process of patient selection is done properly, any one of these three strategies can be used successfully.
Assuntos
Acomodação Ocular/efeitos dos fármacos , Soluções Oftálmicas/administração & dosagem , Guias de Prática Clínica como Assunto , Presbiopia/tratamento farmacológico , Acuidade Visual , Humanos , Presbiopia/fisiopatologiaRESUMO
PURPOSE: To evaluate the safety, efficacy, and patient satisfaction with a pharmacological treatment of presbyopia performed with the Benozzi's method. METHODS: A non-randomized multicentric case-series retrospective study was developed. Were included patients from 5 centers of Argentina, from January 2010 to June 2019, aged at baseline between 40 and 60 years old, with binocular uncorrected distance visual acuity (UDVA) of 25/20 or better, and with uncorrected near visual acuity (UNVA) at least Jaeger (J) 2 or worse. The treatment was performed with a patented formulation (pilocarpine and diclofenac preservative-free eye drops). The main outcome was binocular UNVA and UDVA. Differences were evaluated by paired t-test. The presence of side effects and patient's satisfaction were also evaluated. Data was analyzed in separated groups according to their follow-up time, from 2 to 10 years. RESULTS: A total of 148 patients were included. At baseline, the UNVA for the different groups were between J3 and J8 which was improved to J1 to J2. The mean baseline UDVA has been ranged between 0.02 and 0.04 logMAR. The mean baseline UDVA has been ranged between 0.02 to 0.04 logMAR, after treatment were between 0.01 to 0.03, without a statisticallysignificant improvement. Side effects were spontaneously resolved, and subjective evaluation shows that patients were satisfied. CONCLUSIONS: This first multicentric shows that Benozzi's method for presbyopia treatment was safety and improves the UNVA without affecting the UDVA, maintaining their efficacy even after 10 years, in a population aged between 40 and 60 years old, from different ophthalmic centers in Argentina.
Assuntos
Presbiopia , Adulto , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Presbiopia/tratamento farmacológico , Refração Ocular , Estudos Retrospectivos , Resultado do Tratamento , Visão Binocular , Acuidade VisualRESUMO
We reported previously that the rat submandibular gland is able to release nanovesicles capable to hydrolyse millimolar concentrations of ATP, ADP and AMP in vitro. Here, we show that rat saliva also contains nanovesicles with the ability to hydrolyse ATP. Our aim was to identify and characterize vesicular nucleotidases by using kinetic, immunological and in silico approaches. Nucleotidase activity in the absence or presence of specific inhibitors allowed us to assume the participation of NTPDase1, -2 and -3, together with ecto-5'-nucleotidase, confirmed using specific antibodies. At neutral pH, initial ATPase activity would be mostly due to NTPDase2, which was thereafter inactivated, leaving NTPDase1 and NTPDase3 to hydrolyse ATP and ADP with an efficacy ATPase/ADPase around 2. Ecto-5'nucleotidase would be mainly responsible for AMP hydrolysis and adenosine accumulation. We proposed a kinetic model for NTPDase2 as a tool to isolate and analyse the turnover of this enzyme in the presence of different ATP concentrations, including those expected in extracellular media. Our study characterizes the ectonucleotidases carried by extracellular vesicles which contribute to modulate ATP and adenosine concentrations in the oral cavity, essential players in purinergic signalling.
Assuntos
5'-Nucleotidase/metabolismo , Vesículas Extracelulares/metabolismo , Boca/metabolismo , Pirofosfatases/metabolismo , Saliva/enzimologia , Proteínas e Peptídeos Salivares/metabolismo , Transdução de Sinais , Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Ratos , Ratos WistarRESUMO
Here, we report that the genetic structure of Tn1331 remained conserved in Argentina from 1989 to 2013 (72 of 73 isolates), with the exception being the plasmid-borne Tn1331-like transposon Tn6238 containing a new aac(6')-Ib-cr allele recovered from a colistin-resistant Klebsiella pneumoniae clinical isolate. A bioinformatic analysis of aac(6')-Ib-like gene cassettes suggests that this new aac(6')-Ib-cr allele emerged through mutation or homologous recombination in the Tn1331 genetic platform. Tn6238 is a novel platform for the dissemination of aminoglycoside and fluoroquinolone resistance determinants.
Assuntos
Genes Bacterianos/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Biologia Computacional , Farmacorresistência Bacteriana/genética , Fluoroquinolonas/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
OBJECTIVE: To investigate the association among rheumatoid arthritis (RA), saliva production, and periodontal status. METHODS: An observational study was carried out on 103 subjects with RA and 103 without RA matched by sex and age. Rheumatologic evaluation included serological and clinical variables. A full mouth periodontal examination was performed according to the American Academy of Periodontology (1999). Resting and stimulated whole salivary flows were determined after spiting during 5 min. RESULTS: RA was associated with a higher prevalence of severe periodontitis (12% vs. 4%), with a marked reduction in resting and stimulated saliva production, and with a higher prevalence of resting (19% vs. 0%) and also stimulated hyposalivation (54% vs. 10%), compared with the control group. The differences in mean resting and stimulated salivary flows between RA and control groups persisted after the exclusion of people with hyposalivation. Saliva production was not associated with the presence or the severity of periodontal disease, or with the rheumatic clinical characteristics of the patients. CONCLUSIONS: More than 50% of people with RA have some degree of reduction in their salivary flows, an affection not associated with the periodontal status or rheumatic activity, which are the expression of the two related inflammatory diseases. The influence of autonomic dysfunction on hyposalivation can be considered. While periodontitis would be a disease-associated comorbidity of RA, poor saliva production should be included among the extra-articular manifestations. Key Points ⢠Rheumatoid arthritis patients are more prone to suffer from periodontitis and/or hyposalivation. ⢠Periodontal disease is more prevalent in people with rheumatoid arthritis and also an association was found between the severities of both pathologies. ⢠More than 50% of people with RA would have some degree of reduction in their salivary flows, an affection not associated with the periodontal status or rheumatic activity. ⢠Reduced saliva production in rheumatoid arthritis patients should be included among the extra-articular manifestations.
Assuntos
Artrite Reumatoide , Doenças Periodontais , Periodontite , Xerostomia , Humanos , Doenças Periodontais/complicações , Doenças Periodontais/epidemiologia , Doenças Periodontais/metabolismo , Periodontite/complicações , Periodontite/epidemiologia , Xerostomia/epidemiologia , Saliva/metabolismoRESUMO
Accommodation is the change in dioptric power of the eye. It is a dynamic process that allows focusing on an object at all distances. In order to focus sharply, three physiological responses, known as the triad of accommodation, are produced by a change in pupil size, a change in shape and position of the lens, and ocular convergence. This is modulated by the autonomic nervous system, mainly the parasympathetic nervous system. Presbyopia is a refractive condition that occurs with aging, usually manifesting around 40-50 years of age, and is a result of the loss of accommodation in the eye, causing loss of visual performance when focusing on objects placed at different distances, starting with near vision. Glasses, contact lenses, surgical approaches and now pharmacological treatments are accepted methods of treating presbyopia. Pharmacological treatment is a promising new noninvasive option for treating presbyopia. Currently there are three pharmacological approaches to the treatment of presbyopia. The first one aims to produce miosis and, from a pinhole effect, increase depth of focus, and therefore improve uncorrected near visual acuity (UNVA). The second one addresses rehabilitating accommodation in a binocular way, allowing good vision at all distances. Finally, the third strategy uses lipoic acid to restore the lost elasticity of the lens. All of these pharmacological treatments are topical non-invasive eyedrops, with no serious adverse effects having been reported with any of the strategies, and require the right patient selection process to fulfill expectations and needs. The aim of this article is to provide an update on recent advances in this field.
Assuntos
Presbiopia , Humanos , Presbiopia/tratamento farmacológico , Presbiopia/cirurgia , Acuidade Visual , EnvelhecimentoRESUMO
Purpose: Regression of the refractive outcome is a major concern of LASIK procedures mainly in presbyopic patients. The purpose of this study was to evaluate the long-term efficacy of the pharmacological treatment of presbyopia performed with Benozzi's method, in combination with hyperopic LASIK surgery in presbyopic population. Methods: A nonrandomized case series was developed, including presbyopic patients who underwent bilateral "Hyperopic LASIK surgery" and were pharmacologically treated with Benozzi's Method from January 2011 to August 2018, with at least 2 years of follow-up, at two private ophthalmological clinics of Argentina. Main outcomes were spherical equivalent (SE), uncorrected distance visual acuity (UDVA), and uncorrected near visual acuity (UNVA). Measurements were evaluated at baseline and postoperative at 1 month (without Benozzi's treatment), 2 months (starting with Benozzi's treatment), and 2 years. The SE stability across the time was statistically compared. Results: A total of 84 eyes of 42 patients, with a mean age at the time of the surgery of 51.07 ± 4.5 (42-59), were found following 2 years of follow-up. Patients have improved and maintained UDVA, achieving Jaeger 1 in the second postoperative month, which was maintained up to the last year of follow-up. Refractive stability across the time is observed comparing first month after surgery with the last year of follow-up, without statistical significant difference (p: 0.11). Conclusion: Hyperopic presbyopic patients that underwent LASIK surgery and 1 month after surgery started with the pharmacological treatment of presbyopia (Benozzi's method) results in excellent UNVA and UDVA that is stable over time without refractive regression.
Assuntos
Hiperopia , Ceratomileuse Assistida por Excimer Laser In Situ , Presbiopia , Humanos , Ceratomileuse Assistida por Excimer Laser In Situ/efeitos adversos , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Resultado do Tratamento , Presbiopia/tratamento farmacológico , Presbiopia/cirurgia , Seguimentos , Lasers de Excimer/uso terapêutico , Hiperopia/tratamento farmacológico , Hiperopia/cirurgiaRESUMO
Local anaesthetics are drugs that prevent or relieve pain by interrupting nervous conduction and are the most commonly used drugs in dentistry. Their main targets of action are voltage-dependent Na+ channels. The Na+ channel is modulated by phosphorylation of two enzymes: PKA (protein kinase A) and PKC (protein kinase C). We studied the ability of lidocaine to modulate programmed cell death of human gingival fibroblasts and the mechanisms involved in this process. Lidocaine (10-5 to 10-7 M) stimulated apoptosis in primary cultures and the caspase-3 activity in a concentration-dependent manner. The stimulatory effect of lidocaine on apoptosis was attenuated in the presence of HA 1004 (PKA inhibitor) and stimulated by staurosporine and Go 6976 (PKC inhibitors). Lidocaine-induced apoptotic nuclei correlated positively with cAMP accumulation and negatively with PKC activity. These results show that lidocaine promotes apoptosis in human gingival fibroblasts at concentrations used for local anaesthesia. The mechanism involves PKA stimulation and PKC inhibition, which in turn stimulates caspase-3 and leads to programmed cell death.
Assuntos
Apoptose/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Gengiva/efeitos dos fármacos , Lidocaína/farmacologia , Proteína Quinase C/metabolismo , Carbazóis , Caspase 3/metabolismo , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Fibroblastos/metabolismo , Gengiva/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Isoquinolinas/farmacologia , Proteína Quinase C/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Estaurosporina/farmacologia , Sulfonamidas/farmacologiaRESUMO
Purpose: The purpose of this study was to evaluate the safety and efficacy across time, of patients topically treated with Benozzi's method for presbyopia. Methods: A nonrandomized case series retrospective study was developed, including patients with emmetropia with binocular uncorrected distance visual acuity (UDVA) of 25/20 or better, and with uncorrected near visual acuity (UNVA) at least Jaeger 2 or worse. The study was set in Buenos Aires, Argentina, from January 2011 to June 2018, with at least 1-year follow-up. Patients were treated with pilocarpine and diclofenac preservative-free eye drops (Benozzi Method; US 8.524.758 B2, EP1.938.839 B1), and the main outcome measured was binocular UNVA at different follow-up times. Other parameters, as the UDVA and presence of side effects, were evaluated. Results: A total of 910 patients were included with a mean age at baseline of 48.67 ± 3.72 years old (range, 40-59 years). The baseline UNVA was 4.74 ± 1.53 and at 8 years of follow-up was decreased to 1.36 ± 0.48 (Jaeger scale). The mean binocular UDVA at baseline was 0.00 ± 0.01 logarithm of the minimum angle of resolution (logMAR) and after 8 years of follow-up was 0.03 ± 0.04 logMAR. All side effects reported (decrease of light perception, headaches, symptoms of ocular surface dryness, and dizziness) were spontaneously resolved in patients who continued with the treatment. Conclusions: The efficacy of the pharmacological treatment of presbyopia to improve the UNVA without affecting the UDVA is shown. Side effects were well tolerated and resolved before 1 year of treatment. Translational Relevance: This is a nonsurgical option for patients with emmetropic presbyopia who do not wish to wear glasses, which is a pharmacological treatment with eye drops.
Assuntos
Presbiopia , Adulto , Argentina , Humanos , Pessoa de Meia-Idade , Soluções Oftálmicas , Presbiopia/tratamento farmacológico , Refração Ocular , Estudos RetrospectivosRESUMO
Down syndrome (DS) presents with prevalent diseases in the oral cavity and the need of constant dental care and follow-up. The use of conscious sedation (CS) for dental care in adult DS with behavioral disorders is poorly documented. The aim of this study was to evaluate the effectiveness and safety of CS procedures with oral midazolam using previous psychoprophylaxis sessions in DS adult patients with behavioral disorders. METHODS: Twenty-nine DS adults with behavioral disorders. The patients were managed with psychoprophylaxis followed by oral CS using 15 or 30 mg midazolam. Vital parameters were monitored. The Houpt and Brietkopf and Buttner scales were used. RESULTS: Patients under CS received an initial dose of 15 mg midazolam; however, 51.72% needed a 30 mg dose at the following sessions. Results showed that 71.4% treated with the 15 mg dose had Houpt scale overall behavior scores of 4 or 5, while 93.33% of those receiving 30 mg had scores of 5 or 6 (chi-square = 15.95 p < .01). CONCLUSION: Psychoprophylaxis sessions followed by CS procedures using oral midazolam in adult DS with behavioral disorders were shown to be a useful strategy to perform routine dental treatment safely. Midazolam produces anterograde amnesia, and participants were more cooperative in the following visits.
Assuntos
Anestesia Dentária , Síndrome de Down , Administração Oral , Adulto , Sedação Consciente , Assistência Odontológica , Humanos , Hipnóticos e SedativosRESUMO
BACKGROUND: Extracellular vesicles released by different cells have been isolated from diverse fluids including saliva. We previously reported that rat submandibular glands secrete nanovesicles that catalyze hydrolysis of ATP, ADP and AMP, which are actors of the purinergic signaling system along with adenosine. Extracellular nucleotides like ATP and adenosine are involved in the regulation of inflammatory processes and apoptosis. Histamine, a widely distributed biogenic amine, is involved in inflammatory response. OBJECTIVE: To test if activation of histamine receptors in rat submandibular gland promotes changes in the release of vesicles with nucleotidase activity that could modulate purinergic signaling. METHODS: Rat submandibular glands were incubated in the absence or presence of histamine and JNJ7777120, an antagonist for H4 receptors. Extracellular vesicles were isolated from incubation media by differential centrifugation. Vesicular nucleotidase activity was measured following Pi release by 3mM MgATP, MgADP or MgAMP. RESULTS: Histamine increased the release of vesicles with nucleotidase activity in a concentration dependent manner. JNJ7777120 significantly reduced this effect. Vesicular nucleotidases obtained in the absence or presence of histamine promoted Pi production from ATP, ADP and AMP. CONCLUSION: The results show a relationship between histamine and the regulation of purinergic signaling, which could be important in the modulation of inflammatory processes.
Assuntos
Vesículas Extracelulares/enzimologia , Histamina/farmacologia , Nucleotidases/metabolismo , Glândula Submandibular/metabolismo , Animais , Técnicas In Vitro , Indóis/farmacologia , Masculino , Microscopia Eletrônica de Transmissão , Piperazinas/farmacologia , Ratos , Ratos WistarRESUMO
Alpha 1 adrenoceptor (alpha1-AR) regulation of DNA synthesis was studied in human neonatal foreskin fibroblast. Saturation assay with a specific radioligand for alpha1 adrenergic [3H]-prazosin revealed two saturated and specific binding sites with high or low affinity. Competitive binding assay with different antagonist subtypes, defined pharmacologically three major types of alpha1-AR. The alpha1-AR agonists (from 1x10(-10) to 1x10(-4) M) triggered a biphasic action on DNA synthesis reaching maximal stimulation at 1x10(-9) M and maximal inhibition at 1x10(-6) M. Prazosin, abolished the stimulatory (pA2: 9.24) and inhibitory (pA2: 8.80) actions of alpha1-AR agonists. The alpha1-AR stimulation resulted in the activation of phosphoinositide turnover (InsP) via phospholipase C (PLC) involving calcium/calmodulin (CaM) and nitric oxide synthase (NOS) that correlates with the DNA synthesis increment; whereas the inhibition resulted in a decrease of cyclic AMP (cAMP) accumulation via adenylate cyclase inhibition. The potency displayed by the specific antagonists tested in binding, DNA synthesis, InsP and NOS at low agonist concentration suggests that they can be elicited by the activation of the same receptor (alpha1B-AR subtype); while the decrement in DNA synthesis and cAMP at high concentration account by the activation of alpha1D-AR coupled to Gi protein. Non-functional alpha1A-AR in neonatal human foreskin fibroblast was observed. Results suggest that the expression of alpha1-AR subtypes on human skin fibroblast may differentially activate signaling pathways that modulate physiological response of the cells.
Assuntos
DNA/biossíntese , Fibroblastos/metabolismo , Receptores Adrenérgicos alfa 1/fisiologia , Agonistas Adrenérgicos/farmacologia , Antagonistas Adrenérgicos/farmacologia , Agonistas de Receptores Adrenérgicos alfa 1 , Antagonistas de Receptores Adrenérgicos alfa 1 , Ligação Competitiva , Técnicas de Cultura de Células , Células Cultivadas , Meios de Cultura Livres de Soro , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Fibroblastos/enzimologia , Humanos , Fosfatos de Inositol/metabolismo , Óxido Nítrico Sintase/metabolismo , Ensaio Radioligante , Timidina/metabolismoRESUMO
The presence of circulating antibodies from primary Sjögren Syndrome (pSS) patients enable to interact with rat cerebral frontal cortex by activating muscarinic acetylcholine receptors (mAChR). ELISA assay for PGE2 generation, nitric oxide synthase (NOS) activity was measured in cerebral frontal cortex slices by production of [U-14C]-citruline and mRNA isolation/quantitative PCR for COX-1 and COX-2 gene expression were carried out. By ELISA assay, it was shown that IgG from pSS patients reacted to cerebral frontal cortex cell surface and with human M1 and M3 mAChR. Beside pSS IgG displayed an agonistic-like activity stimulating NOS activity and PGE2 production associated with an increased COX-1 mRNA gene expression, without affecting COX-2 mRNA levels. Inhibition of phospholipase A2 (PLA2) and NOS prevented pSS IgG effects upon both PGE2 production and COX-1 mRNA levels. The results support the notion that serum IgG auto antibodies in pSS patients target cerebral mAChR may have pathogenic role in immune neuroinflammation and on cognitive dysfunction present in pSS patients.
Assuntos
Autoanticorpos/farmacologia , Córtex Cerebral/efeitos dos fármacos , Dinoprostona/metabolismo , Óxido Nítrico/metabolismo , Síndrome de Sjogren/imunologia , Adulto , Animais , Autoanticorpos/imunologia , Córtex Cerebral/imunologia , Córtex Cerebral/metabolismo , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 2/genética , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/farmacologia , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Antagonistas Muscarínicos/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Inibidores de Fosfolipase A2 , Piperidinas/farmacologia , Pirenzepina/farmacologia , Ratos , Ratos Wistar , Receptores Muscarínicos/metabolismoRESUMO
In this study we determined the effect of cholinoceptor agonist pilocarpine on the stimulation of nitric oxide synthase (NOS) and on prostaglandin E2 (PGE2) generation upon rat dental pulp. By reverse transcriptase/polymerase chain reaction (RT-PCR) we identified several products corresponding to m1, m2, m3, and m4 muscarinic acetylcholine receptors (mAChRs). The stimulation of M1, M2, M3, and M4 mAChRs by pilocarpine increases NOS activity and PGE2 generation. There is a correlation (correlation coefficient=0.05) between NOS activity and PGE2 generation through the activation of phosphoinositide by phospholipase C (PLC), phospholipase A2 (PLA2), and cyclooxygenase 1 (COX-1). Exogenous PGE2 restored NOS activity inhibited by indomenthacin (INDO), whereas nitric oxide (NO) donor restored PGE2 generation inhibited by NG-methyl-L-arginine acetate salt (L-NMMA). These data indicate that both NO and PGE2 interact with their own respective biosynthetic pathways modulating NOS and COX activities. Results could contribute to understanding the involvement of NO and PGE2 in healthy dental pulp given that cellular signals through the parasympathetic system modulate the function of the dentin-pulp complex.
Assuntos
Polpa Dentária/metabolismo , Dinoprostona/metabolismo , Agonistas Muscarínicos/farmacologia , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico/metabolismo , Pilocarpina/farmacologia , Receptores Muscarínicos/metabolismo , Análise de Variância , Animais , Vias Biossintéticas , Ciclo-Oxigenase 1/metabolismo , Polpa Dentária/efeitos dos fármacos , Ativação Enzimática , Isoenzimas , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Regulação para CimaRESUMO
In this paper we have determined the different signal pathways involved in M(1) and M(3) muscarinic acetylcholine receptor (mAChR) dependent stimulation of cyclo-oxygenase 1 (cox-1) mRNA gene expression and PGE(2) production on rat cerebral frontal cortex. Carbachol stimulation of M(1) and M(3) mAChR exerts an increase in cox-1 mRNA gene expression without affecting cox-2 mRNA expression and increased PGE(2) generation. Besides, increased phosphoinositide (PI) turnover and stimulation of nitric oxide synthase (NOS) and cyclic GMP (cGMP) production. Inhibitors of phospholipase A(2) (PLA(2)), COX and phospholipase C (PLC), calcium/calmodulin (CaM), NOS and soluble guanylate cyclase prevent the carbachol effect. These results suggest that carbachol-activation of M(1) and M(3) mAChR increased PGE(2) release associated with an increased expression of cox-1 and NO-cGMP production. The mechanism appears to occur directly to PLC stimulation and indirectly to PLA(2) activation. These results may contribute to understand the effects and side effect of non-steroidal anti-inflammatory drugs in patients with cerebral degenerative diseases.
Assuntos
Carbacol/farmacologia , Agonistas Colinérgicos/farmacologia , Dinoprostona/metabolismo , Lobo Frontal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Prostaglandina-Endoperóxido Sintases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , GMP Cíclico/metabolismo , Ciclo-Oxigenase 1 , Relação Dose-Resposta a Droga , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Lobo Frontal/metabolismo , Masculino , Proteínas de Membrana , Modelos Biológicos , Antagonistas Muscarínicos/farmacologia , Óxido Nítrico Sintase/metabolismo , Fosfatidilinositóis/metabolismo , Piperidinas/farmacologia , Pirenzepina/farmacologia , Prostaglandina-Endoperóxido Sintases/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
We have developed a novel typing method based on Vibrio cholerae repeat sequences (VCR) using primers directed out of the VCR sequences. To evaluate the VCR-polymerase chain reaction (PCR) as a typing system, 2 categories, efficacy and efficiency, were analyzed in 69 strains of human and environmental V. cholerae O1 toxigenic and nontoxigenic, and non-O1 strains isolated since 1992-2000 from Argentina. The discriminatory power (0.91), stability (0.95), reproducibility (1), typeability (1), rapidity, accessibility, as well ease of use, indicated that the VCR-PCR method provides an alternative useful tool for molecular epidemiology of V. cholerae. The VCR-PCR of V. cholerae isolates showed 29 patterns, of which pattern 1 represented 68% of the V. cholerae O1 isolates, supporting the hypothesis that a clone with epidemic behavior was responsible for the epidemic in Latin America. These results showed a good correlation and a better epidemiologic analysis when the results were compared in parallel with repetitive extragenic palindromic sequences-PCR. In conclusion, VCR-PCR showed excellent performance as a typing method for cholera surveillance programs.
Assuntos
Técnicas de Tipagem Bacteriana , Surtos de Doenças , Reação em Cadeia da Polimerase/métodos , Sequências Repetitivas de Ácido Nucleico/genética , Vibrio cholerae O1/classificação , Vibrio cholerae não O1/classificação , Argentina/epidemiologia , Cólera/epidemiologia , Cólera/microbiologia , DNA Bacteriano/análise , Microbiologia Ambiental , Humanos , Vibrio cholerae O1/genética , Vibrio cholerae O1/isolamento & purificação , Vibrio cholerae não O1/genética , Vibrio cholerae não O1/isolamento & purificaçãoRESUMO
Previous studies have demonstrated that antibodies against muscarinic acetylcholine receptors (mAChRs) from exocrine glands, correlates with Sjögren syndrome (SS) in the majority of patients. The aim of the present investigation was to establish if serum IgG antibodies present in SS interacts with cerebral mAChRs. Results show that anti-cerebral IgG are present in the sera of 40% SS patients studied. Autoantibodies were able to interact with mAChRs of cerebral frontal cortex membranes inhibiting the [(3)H]QNB binding to its specific receptor. Moreover, tested by ELISA and dot blot they recognized the synthetic peptides corresponding to the second extracellular loop of human M(1) and M(3) mAChR. In addition, the corresponding affinity-purified anti-M(1) and anti-M(3) peptide IgGs displayed an agonistic activity, stimulating phosphoinositide hydrolysis. The results support the notion that serum IgG autoantibodies in SS patients target cerebral mAChRs may have some role in the pathogenesis of higher cognitive dysfunction present in SS patients.
Assuntos
Autoanticorpos/fisiologia , Lobo Frontal/imunologia , Receptor Muscarínico M1/imunologia , Receptor Muscarínico M3/imunologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Adulto , Sequência de Aminoácidos , Animais , Autoanticorpos/sangue , Autoanticorpos/metabolismo , Sítios de Ligação de Anticorpos/imunologia , Ligação Competitiva/imunologia , Feminino , Lobo Frontal/metabolismo , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/metabolismo , Imunoglobulina G/fisiologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fosfatidilinositóis/biossíntese , Estrutura Secundária de Proteína , Ratos , Receptor Muscarínico M1/fisiologia , Receptor Muscarínico M3/fisiologia , Regulação para Cima/imunologiaRESUMO
In this paper we demonstrated that lidocaine broadens the therapeutic range of ouabain action having a protective effect on ouabain-induced toxicity on rat atria. The lidocaine effect on therapeutic ouabain action was associated with the increase in the sensitivity of Na(+)-K(+)-ATPase related to a decreased in the equilibrium dissociation constant (K(d)) of high affinity binding sites. Lidocaine suppressed the ouabain-induced tonotropic effect and arrhythmias, decreasing the number of low affinity binding sites (B(max)) without changes in K(d). Blockade of Na(+)-Ca(2+) exchange with KB-R7943 or dual Na(+)-Ca(2+) channel with flunarizine, mimicked lidocaine effect increasing ouabain therapeutic action, extending its concentration range tolerated, delaying the onset of contracture. Lidocaine itself triggered negative inotropic response at high concentration. This effect was increased in the presence of flunarizine and verapamil but not by the inhibition of calcium/calmodulin with W-7. The mechanism underlying the lidocaine-induced negative inotropic response, appears to be different that underlying the positive inotropic effect on ouabain action. This study provides evidence that lidocaine can interact with the same or similar binding sites for ouabain in rat atrial tissue, providing a protective effect on ouabain-induced changes in contractility. The contribution of Na(+)-Ca(2+) exchange and/or Ca(2+) overload on lidocaine effect is discussed.
Assuntos
Função Atrial/efeitos dos fármacos , Lidocaína/farmacologia , Contração Miocárdica/efeitos dos fármacos , Ouabaína/farmacologia , Tioureia/análogos & derivados , Animais , Antiarrítmicos/farmacologia , Função Atrial/fisiologia , Bloqueadores dos Canais de Cálcio/farmacologia , Cardiotônicos/farmacologia , Interações Medicamentosas , Flunarizina/farmacologia , Átrios do Coração/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Sulfonamidas/farmacologia , Tioureia/farmacologiaRESUMO
We demonstrate that changes in the behaviour of the contractile ciliary muscle accompanied by augmented rigidity of the lens are the most important aspects in the loss of accommodation. With ultrabiomicroscopy (UBM), we demonstrated that the performance of the ciliary muscle is diminished and accompanied by rigidity of the lens. Both lens thickness and trabecular-ciliary process distance (TCPD) were the parameters that showed major alterations with the loss of accommodation in patients of different ages. The results indicated that the differences between these parameters in farsightedness and nearsightedness in the different groups of patients were positively correlated.