The efficacy of the diode laser at 800-980 nm as an aid to non-surgical therapy in periodontitis treatment: a review of literature.

The aim of this literature review is to assess the effectiveness of diode laser at a wavelength of 800-980 nm in addition to non-surgical periodontal therapy in periodontitis treatment. The authors performed an electronic research on Pubmed inserting as keywords: (laser OR laser therapy OR diode laser) and (periodontitis OR periodontal disease). The field has been narrowed to select only Randomized controlled clinical trials (RCT) performed from 2010 to 2020. The result of this research was 84 articles, of which eight were included in the review because they respect the inclusion criteria. The clinical, immunological, and microbiological parameters studied in the various clinical random trials were analysed. It has been shown that four out of eight studies have achieved greater benefits, in terms of clinical parameters, with the use of diode laser compared to Scaling and Root Planing. However, the greater increase in clinical parameters in diode laser-treated patients compared to the control group was mainly detected in the short term rather than in the long term. In terms of microbiological parameters, no improvement was detected after six months. Only one study reported six-month improvements in immunological parameters in patients treated with DL compared to the Scaling and Root Planing only group. In conclusion, considering the limitations of this review of literature, there is no evidence that the diode laser at 800-980 nm in addition to non-surgical periodontal therapy is more effective than SRP alone in the long term.

Frequency of psychological alterations in primary antiphospholipid syndrome: preliminary study.

Objectives To detect the frequency of psychological alterations in primary antiphospholipid syndrome patients. Methods Thirty-six primary antiphospholipid syndrome patients were analyzed by a psychological interview using a standard protocol and review of medical charts. Clinical manifestations, associated comorbidities, antiphospholipid antibodies, and treatment were also evaluated. Results The mean age was 44.2 ± 10.8 years, 29 (80%) were women and 29 (80%) were of Caucasian race. The mean duration of disease was 7.3 ± 5.2 years. The frequency of the presence of psychological alterations was 97.1%. Family dependence was observed in 14 (40%), memory loss in 12 (34.3%), social losses in 12 (34.3%), sexual limitations in seven (20%), sadness in six (17.1%), severe speech limitation in four (11.4%), anxiety in three (8.6%), learning difficulty in two (5.7%), generalized phobia in two (5.7%), suicide ideation in one (2.6%), agoraphobia in one (2.6%), and obsessive-compulsive disorder in one (2.6%). Conclusion This study demonstrated that almost all primary antiphospholipid syndrome patients have psychological alterations. These data reinforce the need for psychological evaluation in primary antiphospholipid syndrome patients.

Apheresis treatment of cryoglobulinemic vasculitis: A multicentre cohort study of 159 patients.

OBJECTIVE: To assess the effectiveness of apheresis therapy (AT) in treating the clinical manifestations of patients with complicated cryoglobulinemic vasculitis (CV). METHODS: A retrospective cohort study of 159 CV patients attending 22 Italian Centers who underwent at least one AT session between 2005 and 2015. The response to AT was evaluated on the basis of a defined grading system. RESULTS: Peripheral neuropathy was the most frequent clinical condition leading to AT. Therapeutic plasma exchange was used in 70.4% of cases. The outcome of AT was rated very good in 19 cases, good in 64, partial/transient in 40, and absent/not assessable in 36. Life-threatening CV-related emergencies and renal impairment independently correlated with failure to respond to AT. The independent variables associated with an increased risk of death were age at the time of the first AT session, multi-organ life-threatening CV, the presence of renal impairment and failure to respond to AT. The time-dependent probability of surviving until CV-related death in the second year was 84%, with an AHR in patients with absent/not assessable response to AT of 11.25. CONCLUSION: In this study AT is confirmed to be a safe procedure in patients with CV. Early AT should be considered in patients with severe CV, especially in cases with impending renal involvement, in order to prevent irreversible kidney damage. Although its efficacy in patients with multi-organ failure is limited, AT is the only treatment that can rapidly remove circulating cryoglobulins, and should be considered an emergency treatment.

Protective effects of Syzygium cumini seed extract against methylmercury-induced sistemic toxicity in neonatal rats.

Syzygium cumini (L.) Skeels (Sc) belongs to the medicinal plants with an important source of phenolic compounds. Sc has been shown to possess antioxidant and anti-inflammatory properties. Methylmercury (MeHg), a highly toxic environmental pollutant, induces oxidative stress and dysfunction in many cell types. This study was aimed to evaluate the effect of aqueous seed extract of Sc (ASc) on MeHg-induced toxicity in rats. Two-day-old rats (P2) received a single dose of MeHg (10 mg/kg) and two doses of ASc (0.9 mg/kg) per os. After two days, the effects of the treatment were investigated in the cerebral cortex, hippocampus, kidney, liver and urine samples. Our results demonstrated that N-acetyl-ß-D: -glucosaminidase (NAG) activity in the kidney and urine, the lipid peroxidation levels in the liver and kidney samples, as well as the adenosine deaminase (ADA) activity in the hippocampus, kidney and liver were higher in MeHg-group when compared to the control group. The administration of ASc reverted the toxic effects of MeHg. It is noteworthy to observe that the main compounds present in the ASc, as gallic acid (the major component), chlorogenic acid and rutin, might be the responsible for such benefit, since they were found to display antioxidant properties.

Assessment of uric acid and lipid peroxidation in serum and urine after hypoxia-ischemia neonatal in rats.

The aim of this study was to evaluate urinary uric acid (UA) and lipid peroxidation levels, plasma myeloperoxidase (MPO) and adenosine deaminase (ADA) activities, and serum UA in neonatal rats subjected to hypoxia-ischemia neonatal HI model. The relevance of the findings is the fact that urinary lipid peroxidation and UA levels were significantly higher in 8 days in HI group when compared with the control, returning to baseline levels 60 days after HI. Hence, being an indication of purinic degradation during these first days post-HI. Furthermore, the higher levels of malondialdehyde (MDA) in urine in this period may be related to inadequate scavenging abilities of the immature nervous system and being noninvasive it may suggest the use of urinary MDA measurement as a marker for lipid peroxidation after HI insult. In application terms, these findings can help develop therapeutic interventions as soon as 8 days after HI.

Decrease of adenosine deaminase activity and increase of the lipid peroxidation after acute methotrexate treatment in young rats: protective effects of grape seed extract.

The methotrexate (MTX) is an anti-folate used to treat cancer and some inflammatory diseases. The efficacy of MTX is often limited by its severe toxicity. The present study was undertaken to determine whether Grape seed (Cabernet Sauvignon) extract (GSE) could ameliorate the MTX-induced oxidative injury and the effect on adenosine deaminase activity (ADA) in rats. The rats were pretreated with 50 mg/kg of GSE, i.p., prior to MTX administration (10 mg/kg, i.p.) with a second dose given 4 h and a third dose 16 h after MTX administration. Biochemical parameters were investigated 48 h after the last MTX administration. The administration of MTX increased thiobarbituric acid reactive species (TBARS) levels in hippocampus, kidney and liver, whereas induced a significant decreased in the ADA activity in the cerebral cortex, kidney and liver tissues. MTX administration significantly increased the activity of ALT(alanine aminotransferase) and urea levels and decreased uric acid levels in the serum. Urinary uric acid levels decreased in the MTX group when compared to those of the control group. The GSE along with MTX-administration significantly reversed these parameters toward to near normal. These results indicated that GSE could reduce hepatic and nephritic damage induced by MTX-treatment in young rats therefore having free radical scavenging.

Effect of different fluoride concentrations of experimental dentifrices on enamel erosion and abrasion.

It has been suggested that fluoride products are able to reduce erosive tooth wear. Thus, the purpose of this in vitro study was to evaluate the effect of dentifrices with different fluoride concentrations as well as of a low-fluoridated dentifrice supplemented with trimetaphosphate (TMP) on enamel erosion and abrasion. One hundred twenty bovine enamel blocks were assigned to the following experimental dentifrices: placebo, 1,100 microg F/g, 500 microg F/g plus 3% TMP and 5,000 microg F/g. The groups of enamel blocks were additionally subdivided into conditions of erosion (ERO) and of erosion plus abrasion (ERO + ABR). For 7 days, the blocks were subjected to erosive challenges (immersion in Sprite 4 times a day for 5 min each time) followed by a remineralizing period (immersion in artificial saliva between erosive challenges for 2 h). After each erosive challenge, the blocks were exposed to slurries of the dentifrices (10 ml/sample for 15 s). Sixty of the blocks were additionally abraded by brushing using an electric toothbrush (15 s). The alterations of the enamel were quantified using the Knoop hardness test and profilometry (measurements in micrometers). The data were analyzed using a 2-way ANOVA test followed by a Bonferroni correction (p < 0.05). In in vitro conditions, the 5,000 microg F/g and 500 microg F/g plus 3% TMP dentifrices had a greater protective effect when compared with the 1,100 microg F/g dentifrice, under both ERO and ERO + ABR conditions. The results suggest that dentifrices alone are not capable of completely inhibiting tooth wear.

Multishell Diffusion MRI-Based Tractography of the Facial Nerve in Vestibular Schwannoma.

BACKGROUND AND PURPOSE: Tractography of the facial nerve based on single-shell diffusion MR imaging is thought to be helpful before surgery for resection of vestibular schwannoma. However, this paradigm can be vitiated by the isotropic diffusion of the CSF, the convoluted path of the facial nerve, and its crossing with other bundles. Here we propose a multishell diffusion MR imaging acquisition scheme combined with probabilistic tractography that has the potential to provide a presurgical facial nerve reconstruction uncontaminated by such effects. MATERIALS AND METHODS: Five patients scheduled for vestibular schwannoma resection underwent multishell diffusion MR imaging (b-values = 0, 300, 1000, 2000 s/mm2). Facial nerve tractography was performed with a probabilistic algorithm and anatomic seeds located in the brain stem, cerebellopontine cistern, and internal auditory canal. A single-shell diffusion MR imaging (b-value = 0, 1000 s/mm2) subset was extrapolated from the multishell diffusion MR imaging data. The quality of the facial nerve reconstruction based on both multishell diffusion MR imaging and single-shell diffusion MR imaging sequences was assessed against intraoperative videos recorded during the operation. RESULTS: Single-shell diffusion MR imaging-based tractography was characterized by failures in facial nerve tracking (2/5 cases) and inaccurate facial nerve reconstructions displaying false-positives and partial volume effects. In contrast, multishell diffusion MR imaging-based tractography provided accurate facial nerve reconstructions (4/5 cases), even in the presence of ostensibly complex patterns. CONCLUSIONS: In comparison with single-shell diffusion MR imaging, the combination of multishell diffusion MR imaging-based tractography and probabilistic algorithms is a more valuable aid for surgeons before vestibular schwannoma resection, providing more accurate facial nerve reconstructions, which may ultimately improve the postsurgical patient's outcome.

Importance of schedule of administration in the therapeutic efficacy of guanosine: early intervention after injury enhances glutamate uptake in model of hypoxia-ischemia.

Perinatal cerebral hypoxia-ischemia (HI) is an important cause of mortality and neurological disabilities such as cerebral palsy, epilepsy, and mental retardation. The potential for neuroprotection in HI can be achieved mainly during the recovery period. In previous work, we demonstrated that guanosine (Guo) prevented the decrease of glutamate uptake by hippocampal slices of neonatal rats exposed to a hypoxic-ischemic (HI) insult in vivo when administrated before and after insult. In the present study, we compared the effect of Guo administration only after HI using various protocols. When compared with the control, a decrease of [(3)H] glutamate uptake was avoided only when three doses of Guo were administered immediately, 24 h and 48 h after insult, or at 3 h, 24 h, and 48 h after injury or at 6 h, 24 h, and 48 h after HI. These findings indicate that early Guo administration (until 6 h) after HI, in three doses may enhance glutamate uptake into brain slices after hypoxia/ischemia, probably resulting in decreased excitotoxicity.

Activity of ectonucleotidases and adenosine deaminase in rats exposed to cigarette smoke.

Cigarette smoke is a complex mixture of various toxic substances that are capable of initiating oxidative damage and promoting blood platelet alterations. In this study, we investigated the activities of the ectoenzymes NTPDase (ectonucleoside triphosphate diphosphohydrolase, CD39) and 5'-nucleotidase (CD73) in platelets as well as adenosine deaminase (ADA) in the plasma of rats exposed to aged and diluted sidestream smoke during 4 weeks. The rats were divided into two groups: I (control) and II (exposed to smoke). After the exposure period, blood was collected and the platelets and plasma were separated for enzymatic assay. The results demonstrated that NTPDase (with ATP as substrate) and 5'-nucleotidase (AMP as substrate) activities were significantly higher in group II (p < 0.05) as compared to group I, while no significant difference was observed for NTPDase with ADP as substrate. The ADA activity was significantly reduced in group II (p < 0.05) as compared with group I. Platelet aggregation was significantly increased in group II (p < 0.05) as compared with group I. We suggest that these alterations in the activity of enzymes from the purinergic system are associated with an increase in platelet aggregation. However, our study has demonstrated that the organism tries to compensate for this enhanced aggregation by increasing hydrolysis of AMP and reducing hydrolysis of adenosine, a potent inhibitor of aggregation and an important modulator of vascular tone.

Ebselen and diorganylchalcogenides decrease in vitro glutamate uptake by rat brain slices: prevention by DTT and GSH.

The purpose of this study was to investigate the possible involvement of the glutamatergic system in the neurotoxicity of diorganylchalcogenides or organochalcogenides from slices of cerebral cortex in different ages of development: 12- and 60-day-old rats. Glutamate uptake was evaluated in cortical slices of 12 and 60 days old rats. Cortex slices were incubated with three different organochalcogenides with or without reduced glutathione or dithiothreitol. At 100 microM, ebselen, diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2 in vitro inhibited the [3H]glutamate uptake in both age. Both 60-day-old rats and for 12-day-old rats, GSH and DTT prevented the (PhTe)2-induced inhibition of glutamate uptake but did not protect the inhibition caused by ebselen and (PhSe)2. These findings suggest that the neurotoxicity of organochalcogenides could be related to their effects on brain glutamate uptake, conceivably involving a redox modulation of reactive amino acids from the glutamate transporter proteins.

Impact of the Ile105Val Polymorphism of the Glutathione S-transferase P1 (GSTP1) Gene on Obesity and Markers of Cardiometabolic Risk in Young Adult Population.

The aim of the study was to investigate the association between Glutathione S-transferase P1 (GSTP1) gene polymorphism with obesity and markers of cardiometabolic risk. A cross-sectional study was carried out in individuals aged≥18 and ≤30 years. The study included 54 normal weight, 27 overweight and 68 obese volunteers. Anthropometric measurements and biochemical parameters were evaluated, the DNA was extracted from blood samples and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure GSTP1 Ile105Val gene polymorphism of the study participants. Also, biochemical analysis and hormone assays were carried out. A positive association between GSTP1 polymorphism and obesity was observed on subjects carrying at least one G allele (AG and GG). GG genotype was found only in the obese group. The G allele carriers presented 2.4 times higher chance of obesity when compared to those with the AA genotype. These results were independent of sex and age. We suggest that despite a study in population regional (south of Brazil), the GSTP1 gene polymorphism may play a significant role in the increase of susceptibility of obesity and contribute to identify the cardiovascular risk in young adults.

Diphenyl ditelluride- and methylmercury-induced hyperphosphorilation of the high molecular weight neurofilament subunit is prevented by organoselenium compounds in cerebral cortex of young rats.

Organotellurides are important intermediates in organic synthesis and, consequently, the occupational exposure to them is a constant risk for laboratory workers. These compounds can elicit many neurotoxic events in the central nervous system (CNS) that are associated with several neurological symptoms. In contrast, organoselenium compounds are considered to exert neuroprotective actions on such effects. Neurofilaments (NF) are important cytoskeletal proteins and phosphorylation/dephosphorylation of NF is important to stabilize the cytoskeleton. In this work we investigated the potential protective ability of the selenium compounds ebselen and diphenyl diselenide (PhSe)(2) against the effect of diphenyl ditelluride (PhTe)(2) and methylmercury (MeHg) on the total (phosphorylated plus nonphosphorylated) and phosphorylated immunocontent of the high molecular weight neurofilament subunit (NF-H) from slices of cerebral cortex of 17-day-old rats. We observed that 1muM MeHg induced hyperphosphorylation, increasing the total immunocontent of this subunit of the high-salt Triton insoluble NF-H. Otherwise, 15muM (PhTe)(2) induced hyperphosphorylation of the high-salt Triton insoluble NF-H without altering the total immunocontent of this protein into the cytoskeletal fraction. Concerning the selenium compounds, 15muM (PhSe)(2) and 5muM ebselen did not induce alteration per se on the in vitro phosphorylation of NF-H. In addition, (PhSe)(2) and ebselen at these concentrations, presented a protective effect against the action of (PhTe)(2) and MeHg, on the immunoreactivity of NF-H. Considering that hyperphosphorylation of NF-H is associated with neuronal dysfunction it is probable that the effects of (PhTe)(2) and MeHg could be related to the remarkable neurotoxicity of these organocalcogenides. Furthermore the neuroprotective action of selenium compounds against (PhTe)(2) and MeHg effects could be a promising route to be exploited for a possible treatment of calcogenides poisoning.

Selenium compounds prevent the effects of methylmercury on the in vitro phosphorylation of cytoskeletal proteins in cerebral cortex of young rats.

In this study we investigated the protective ability of the selenium compounds ebselen and diphenyldiselenide against the effect of methylmercury on the in vitro incorporation of 32P into intermediate filament (IF) proteins from the cerebral cortex of 17-day-old rats. We observed that methylmercury in the concentrations of 1 and 5 microM was able to inhibit the phosphorylating system associated with IF proteins without altering the immunocontent of these proteins. Concerning the selenium compounds, diselenide (1, 15, and 50 microM) did not induce alteration of the in vitro phosphorylation of IF proteins. Conversely, 15 microM diselenide was effective in preventing the toxic effects induced by methylmercury. Otherwise, ebselen induced an altered in vitro phosphorylation of the cytoskeletal proteins in a dose-dependent manner. Ebselen at intermediate concentrations (15 and 30 microM) increased the in vitro phosphorylation. However, at low (5 microM) or high (50 and 100 microM) concentrations it was ineffective in altering the cytoskeletal-associated phosphorylating system. Furthermore, 5 microM ebselen presented a protective effect against the action of methylmercury on the phosphorylating system. In conclusion, our results indicate that the selenium compounds ebselen and diselenide present protective actions toward the alterations of the phosphorylating system associated with the IF proteins induced by methylmercury in slices of the cerebral cortex of rats.

Organoselenium compounds prevent hyperphosphorylation of cytoskeletal proteins induced by the neurotoxic agent diphenyl ditelluride in cerebral cortex of young rats.

In this work we investigated the protective ability of the selenium compounds ebselen and diphenyl diselenide against the effect of diphenyl ditelluride on the in vitro incorporation of 32P into intermediate filament (IF) proteins from slices of cerebral cortex of 17-day-old rats. We observed that ditelluride in the concentrations of 1, 15 and 50 microM induced hyperphosphorylation of the high-salt Triton insoluble neurofilament subunits (NF-M and NF-L), glial fibrillary acidic protein (GFAP) and vimentin, without altering the immunocontent of these proteins. Concerning the selenium compounds, diselenide (1,15 and 50 microM) did not induce alteration of the in vitro phosphorylation of the IF proteins. Otherwise, ebselen induced an altered in vitro phosphorylation of the cytoskeletal proteins in a dose-dependent manner. At intermediate concentrations (15 and 30 microM) it increased the in vitro phosphorylation even though, at low (5 microM) or high (50 and 100 microM) concentrations this compound was ineffective in altering the activity of the cytoskeletal-associated phosphorylating system. In addition, 15 microM diselenide and 5 microM ebselen, presented a protective effect against the action of ditelluride, on the phosphorylation of the proteins studied. Considering that hyperphosphorylation of cytoskeletal proteins is associated with neuronal dysfunction and neurodegeneration, it is probable that the effects of ditelluride could be related to the remarkable neurotoxicity of this organic form of tellurium. Furthermore the neuroprotective action of selenium compounds against tellurium effects could be a promising route to be exploited for a possible treatment of organic tellurium poisoning.

Ebselen protects glutamate uptake inhibition caused by methyl mercury but does not by Hg2+.

Alterations of the neurotransmitter release systems in CNS have been reported in a variety of neuropathological processes associated with heavy metal toxicity. Neurotoxic effects of mercurials were investigated in vitro in cerebral cortex slices from young rats. The present study indicates that: (i) the environmental contaminants methylmercury (MeHg) and mercuric chloride (Hg2+) (50 microM) inhibited the glutamate net uptake from the cerebral cortex of 17-day-old rats; (ii) ebselen (10 microM) reverted the MeHg-induced inhibition of glutamate net uptake but did not protect the inhibition caused by Hg2+. At same time, we investigated another diorganochalcogenide, diphenyl diselenide (PhSe)2 and it was observed that this compound did not revert the action of MeHg or Hg2+; (iii) in addition, we observed that exposure of slices to 50 microM MeHg and Hg2+ for 30 min followed by Trypan blue exclusion assay resulted in 58.5 and 67.5% of staining cells, respectively, indicating a decrease in cell viability. Ebselen protected slices from the deleterious effects of MeHg, but not of Hg2+ on cell viability. Conversely, ebselen did not modify the reduction of MTT caused by MeHg and Hg2+; (iv) the protective effect of ebselen on MeHg-induced inhibition of glutamate net uptake seems to be related to its ability in maintaining cell viability.

Differences in immunological response to a T. gondii protein (SAG1) derived peptide between two strains of mice: effect on protection in T. gondii infection.

This study presents the analysis of the immunogenicity, antigenicity and protective effects of a peptide derived from the major surface antigen of Toxoplasma gondii, SAG1. This synthetic peptide carrying three predicted H-2k restricted T cell epitopes was used to immunize mice. The protective effect of the peptide was evaluated in CBA/J and C57BL/6 mice using the decrease in brain cyst load as evidence of protection. Immunization of C57BL/6 mice yielded high antibody titres but had no protective effect after oral challenge. Immunized CBA/J, mice which responded with a lower titre, showed a 35% reduction in cyst burden after oral challenge. Both strains yielded antibodies which recognized the cognate SAG1 protein on immunoblot assay. Using the BIAcore, system, it was shown that at lower titres the CBA/J mouse sera recognized the native SAG1 protein more effectively than the C57BL/6 mouse sera, yielding much higher anti-peptide titres. Lymphoproliferation assays using the peptide experimentally confirmed the predicted T-cell epitopes and showed that they were also recognized by cells of T. gondii infected mice. The anti-peptide subclass analysis suggested a Th1 orientation in CBA/J mice, whereas a Th2 orientation was observed in C57BL/6 mice. Finally, fine analysis of sequences recognized under MHC class I indicated the existence of a T-cell epitope in the H-2k haplotype (CBA/J mice) but not in the H-2b haplotype (C57BL/6 mice). This study provides a structural basis to the understanding of the vaccination response to one of the T. gondii antigens in different strains of mice.

In Vitro Effects of Resin Infiltration on Enamel Erosion Inhibition.

Resin-based materials that show promising effects for preventing the progression of erosion have been studied. This in vitro study evaluated the effects of applying resin-based materials, including resin infiltration, on previously eroded enamel subjected to erosive challenges. The influence of enamel surface etching prior to application of the material was also studied. Bovine enamel blocks were immersed in hydrochloric acid (HCl), 0.01 M (pH 2.3), for 30 seconds in order to form a softened erosion lesion. The blocks were then randomly divided into nine groups (n=12) and treated as follows: C = control without treatment; Hel = pit & fissure resin sealant (Helioseal Clear); Adh = two-step self-etching adhesive system (AdheSe); Tet = two-step conventional adhesive system (Tetric N-bond); and Inf = infiltrant (Icon). The Helno, Adhno, Tetno, and Infno groups received the same materials without (or with no) surface conditioning. The depth of the material's penetration into softened erosion lesions was qualitatively analyzed using reflection and fluorescence confocal microscopy. After application of the materials, the blocks were immersed in HCl for two minutes; this step was followed by immersion in artificial saliva for 120 minutes four times a day for five days (erosive cycling). Both the enamel alteration and material thickness were analyzed using profilometry, and the results were submitted to Kruskal-Wallis and Dunn tests (p>0.05). Images from the confocal microscopy showed minimal penetration of Adh/Adhno and deep penetration of Inf/Infno into the erosive lesions. The groups Hel, Adh, Inf, Tetno, and Infno resulted in the formation of a layer of material over the enamel, which was effective in inhibiting the progression of erosion. In conclusion, the infiltrant, with or without etching, was able to penetrate and protect the enamel against dental erosion. The other resin-based materials, except for the two-step conventional adhesive, were able to penetrate and inhibit the progression of erosive lesions only when they were applied after enamel etching.

Nitric oxide regulates luteinizing hormone-releasing hormone secretion.

We have analyzed the role of nitric oxide (NO), an unorthodox and novel neuromodulator, on luteinizing hormone-releasing hormone (LHRH) secretion. Sodium nitroprusside (SNP), an NO donor, was used to challenge LHRH neurons using both hypothalamic explants and an immortalized neuronal cell line (GT1 cells) in vitro. In both paradigms, SNP was able to stimulate LHRH release in a dose-dependent manner. This action of SNP was accompanied by an elevation in both extra- and intra-cellular cGMP levels. In addition, exposure of LHRH cells (GT1-7 cells) to increasing concentrations of a soluble analog of cGMP (8-Br-cGMP) enhanced LHRH release in a dose-dependent manner, indicating that LHRH neurons have the intrinsic ability to respond to the intracellular messenger elicited by NO, i.e., cGMP. Furthermore, sodium nitroprusside-induced LHRH secretion from GT1-7 cells was blocked, in a dose-dependent manner, by Rp-8-Br-cGMPS, a cGMP analog which blocks cGMP-dependent protein kinase. These data clearly demonstrate that NO stimulates LHRH secretion by activating guanylate cyclase, and support a potential role of NO as a neuroactive agent involved in the control of LHRH secretion and, thereby, reproductive functions.

Endothelin-3 stimulates luteinizing hormone-releasing hormone (LHRH) secretion from LHRH neurons by a prostaglandin-dependent mechanism.

Endothelin (ET) peptides have recently been recognized as putative regulators of the endocrine system. Particularly in the gonadal system, ET-3 stimulates LH secretion from anterior pituitary cells cultured in vitro. In these studies, we evaluate the actions of ET-3, the most abundant species of the ET family in the central nervous system, on LHRH release from arcuate nucleus-median eminence (AN-ME) fragments and an LHRH-secreting neuronal cell line (GT1 cells) in vitro. ET-3 exhibited a stimulatory effect on LHRH secretion from AN-ME fragments and GT1 cells incubated in a static system as well as in a dynamic perifusion paradigm. In all the systems used, the effects of ET-3 on LHRH secretion showed a dose dependency. The increase in LHRH secretion induced by ET-3 was accompanied by an increased secretion of prostaglandin E2 (PGE2), not only in the AN-ME incubations, but also in the GT1 incubation and perifusion systems. Blockade of arachidonic acid and/or PG synthesis significantly reduced the ET-3-induced LHRH and concomitant PGE2 release from both AN-ME fragments and GT1 cells incubated in vitro. In AN-ME incubations, ET-3 effects were enhanced by potassium-induced depolarization. This suggests that activation of other transmitter system(s) may be needed for obtaining a physiological activation of the LHRH neuronal system. In summary, in these studies we provide evidence for a direct action of ET-3 on the LHRH neuronal system. This action is exerted directly on LHRH neurons either at the level of the nerve terminals, the perikaryon, or both. In addition, the effects of ET-3 on LHRH release require a functional arachidonic acid metabolic pathway, particularly involving PG synthesis, in order to obtain stimulation, indicating that PGs are involved in the intracellular events leading to ET-3-evoked LHRH secretion.