Antinociceptive and Antiallodynic Activity of Some 3-(3-Methylthiophen-2-yl)pyrrolidine-2,5-dione Derivatives in Mouse Models of Tonic and Neuropathic Pain.

Antiseizure drugs (ASDs) are commonly used to treat a wide range of nonepileptic conditions, including pain. In this context, the analgesic effect of four pyrrolidine-2,5-dione derivatives (compounds 3, 4, 6, and 9), with previously confirmed anticonvulsant and preliminary antinociceptive activity, was assessed in established pain models. Consequently, antinociceptive activity was examined in a mouse model of tonic pain (the formalin test). In turn, antiallodynic and antihyperalgesic activity were examined in the oxaliplatin-induced model of peripheral neuropathy as well as in the streptozotocin-induced model of painful diabetic neuropathy in mice. In order to assess potential sedative properties (drug safety evaluation), the influence on locomotor activity was also investigated. As a result, three compounds, namely 3, 6, and 9, demonstrated a significant antinociceptive effect in the formalin-induced model of tonic pain. Furthermore, these substances also revealed antiallodynic properties in the model of oxaliplatin-induced peripheral neuropathy, while compound 3 attenuated tactile allodynia in the model of diabetic streptozotocin-induced peripheral neuropathy. Apart from favorable analgesic properties, the most active compound 3 did not induce any sedative effects at the active dose of 30 mg/kg after intraperitoneal (i.p.) injection.

Synthesis, anticonvulsant, and antinociceptive activity of new 3-(3-methyl-2,5-dioxo-3-phenylpyrrolidin-1-yl)propanamides and 3-phenyl-butanamides.

A focused library of new 3-(3-methyl-2,5-dioxo-3-phenylpyrrolidin-1-yl)propanamides and their nonimide analogs were synthesized and tested for anticonvulsant activity. These compounds were obtained through the coupling reaction of the starting carboxylic acids with appropriate amines. The initial anticonvulsant screening was performed in mice (intraperitoneal administration) using the maximal electroshock seizure (MES) and the subcutaneous pentylenetetrazole (scPTZ) seizure models. The most promising compound 6 showed more potent protection in the MES and scPTZ tests than valproic acid, which is still recognized as one of the most relevant first-line anticonvulsants. The structure-activity relationship analysis revealed that the presence of the pyrrolidine-2,5-dione ring is important but not indispensable to retain anticonvulsant activity. Additionally, compound 6 showed potent antinociceptive properties in the oxaliplatin-induced neuropathic pain model in mice. The most plausible mechanism of action for compound 6 may result from its influence on the neuronal sodium channel (Site 2) and the high-voltage-activated L-type calcium channel.

Synthesis, Anticonvulsant, and Antinociceptive Activity of New 3-(2-Chlorophenyl)- and 3-(3-Chlorophenyl)-2,5-dioxo-pyrrolidin-1-yl-acetamides.

The new series of 3-(2-chlorophenyl)- and 3-(3-chlorophenyl)-pyrrolidine-2,5-dione-acetamide derivatives as potential anticonvulsant and analgesic agents was synthesized. The compounds obtained were evaluated in the following acute models of epilepsy: maximal electroshock (MES), psychomotor (6 Hz, 32 mA), and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The most active substance-3-(2-chlorophenyl)-1-{2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethyl}-pyrrolidine-2,5-dione (6) showed more beneficial ED50 and protective index values than the reference drug-valproic acid (68.30 mg/kg vs. 252.74 mg/kg in the MES test and 28.20 mg/kg vs. 130.64 mg/kg in the 6 Hz (32 mA) test, respectively). Since anticonvulsant drugs are often effective in neuropathic pain management, the antinociceptive activity for two the promising compounds-namely, 6 and 19-was also investigated in the formalin model of tonic pain. Additionally, for the aforementioned compounds, the affinity for the voltage-gated sodium and calcium channels, as well as GABAA and TRPV1 receptors, was determined. As a result, the most probable molecular mechanism of action for the most active compound 6 relies on interaction with neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Compounds 6 and 19 were also tested for their neurotoxic and hepatotoxic properties and showed no significant cytotoxic effect.

The utility of gingival crevicular fluid matrix metalloproteinase-8 provides site-specific diagnostic value for periodontal grading.

INTRODUCTION: Matrix metalloproteinase-8 (MMP-8), and its active form aMMP-8, was identified as a potential biomarker of periodontal tissue destruction. It is present at different concentrations in various oral fluids. MATERIAL AND METHODS: Gingival crevicular fluid (GCF) samples were collected from periodontal pockets ≥ 6 mm of 24 untreated patients using paper points and clinical parameters were recorded. 12 subjects were diagnosed with periodontitis stage III grade B, and 12 others with periodontitis stage III grade C. After thorough preparations, samples were collected following manufacturers' instructions and analyzed using a commercially available test system for aMMP-8 evaluation (aMMP-8 Test) and Periotron 8000 together with Quantikine kits for assessment of total MMP-8 concentration (controls). Microbiological evaluation of the same pockets was carried out using real-time polymerase chain reaction. RESULTS: Concentrations of both total MMP-8 and aMMP-8 in GCF were higher in the case of periodontitis grade C, compared to periodontitis grade B, but reached statistical significance only in the case of total MMP-8 (77.17 ng/ml and 18.73 ng/ml respectively; p = 0.0104). Positive correlations were found between total MMP-8 and aMMP-8 levels and the prevalence of Fusobacterium nucleatum, mean probing pocket depth of all pockets, % of pockets ≥ 6 mm, as well as probing pocket depth of pocket from which GCF samples were collected. CONCLUSIONS: GCF concentration levels of both total MMP-8 and aMMP-8 correlated with severity of periodontal destruction, whereas total MMP-8 appeared to be a preferable method for differentiation of periodontal grading. However, the aMMP-8 Test was easier and more convenient to handle.

The immunomodulating role of probiotics in the prevention and treatment of oral diseases.

Probiotics are defined as non-pathogenic live microorganisms which, when administered in appropriate amounts, are beneficial to the health of the host. Currently, the group of probiotic microorganisms includes bacteria that produce lactic acid of the genera Lactobacillus and Bifidobacterium, belonging to the so-called LAB (lactic acid bacteria) groups, and the yeast Saccharomyces boulardii. Probiotics have a protective role in Candida spp. oral infection and especially colonization. Lactobacillus limits the progression of chronic periodontitis by inhibiting the secretory activity of Th17 lymphocytes, which in the pathogenesis of this disease are responsible for an excessive cytokine response causing adverse changes in periodontal tissues. A meta-analysis of the results of studies on the clinical evaluation of the effectiveness of probiotics in the treatment of gingivitis showed that the use of probiotics improved the condition of the gums in the course of the therapeutic process. Regular use of probiotics during orthodontic treatment significantly reduces the number of bacteria from the Streptococcus mutans group in the patient's saliva and significantly inhibits the expression of inflammatory mediators and an excessive immune response. The main mechanisms of the action of probiotics, such as elimination and inhibition of the growth of pathogenic microorganisms through competition for receptor sites and the secretion of metabolites with antibacterial activity, as well as the stimulation of specific and non-specific immune responses by activating T lymphocytes, and stimulating the production of cytokines, make it possible to also effectively use pro-health bacteria in oral diseases.

Synthesis, Anticonvulsant and Antinociceptive Activity of New Hybrid Compounds: Derivatives of 3-(3-Methylthiophen-2-yl)-pyrrolidine-2,5-dione.

The present study aimed to design and synthesize a new series of hybrid compounds with pyrrolidine-2,5-dione and thiophene rings in the structure as potential anticonvulsant and antinociceptive agents. For this purpose, we obtained a series of new compounds and evaluated their anticonvulsant activity in animal models of epilepsy (maximal electroshock (MES), psychomotor (6 Hz), and subcutaneous pentylenetetrazole (scPTZ) seizure tests). To determine the mechanism of action of the most active anticonvulsant compounds (3, 4, 6, 9), their influence on the voltage-gated sodium and calcium channels as well as GABA transporter (GAT) was assessed. The most promising compound 3-(3-methylthiophen-2-yl)-1-(3-morpholinopropyl)pyrrolidine-2,5-dione hydrochloride (4) showed higher ED50 value than those of the reference drugs: valproic acid (VPA) and ethosuximide (ETX) (62.14 mg/kg vs. 252.7 mg/kg (VPA) in the MES test, and 75.59 mg/kg vs. 130.6 mg/kg (VPA) and 221.7 mg/kg (ETX) in the 6 Hz test, respectively). Moreover, in vitro studies of compound 4 showed moderate but balanced inhibition of the neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Additionally, the antinociceptive activity of the most active compounds (3, 4, 6, 9) was also evaluated in the hot plate test and writhing tests, and their hepatotoxic properties in HepG2 cells were also investigated. To determine the possible mechanism of the analgesic effect of compounds 3, 6, and 9, the affinity for the TRPV1 receptor was investigated.

Is the progression rate of periodontitis related to subgingival biofilm composition or gingival crevicular fluid IL-1ß and MMP-8 concentrations?

AIM OF THE STUDY: To analyze the composition of subgingival biofilm and to assess the concentration of IL-1 and MMP-8 in gingival crevicular fluid (GCF) from deep periodontal pockets in patients with severe periodontitis to determine whether the presence of specific microbial species or the severity of the host's immune response can be helpful in assessing the dynamics of disease. MATERIAL AND METHODS: The study included 30 individuals with periodontitis Grade B and 19 subjects with periodontitis Grade C. Quantitative and qualitative microbiological analysis of flora in pockets ≥ 7 mm was performed for the presence of selected periopathogens of the orange, red complex and Aggregatibacter actinomycetemcomitans using real-time PCR. The concentrations of IL-1 and MMP-8 in GCF were evaluated with the ELISA method. RESULTS: There were no differences in the composition of the subgingival biofilm depending on the diagnosis. The concentration of MMP-8 in GCF was significantly higher in periodontitis Grade C than in periodontitis Grade B (61 ng/µl and 37 ng/µl respectively, p = 0.039). The concentration of IL-1ß was similar in both groups. No significant correlations were observed between the occurrence of individual periopathogens and concentrations of MMP-8 and IL-1ß depending on the diagnosis. CONCLUSIONS: Periodontitis grade may not be distinguished according to microbial analysis of subgingival biofilm or to concentration of IL-1ß in GCF. On the other hand, higher concentrations of MMP-9 in GCF from deep pockets may be helpful in detecting subjects particularly prone to occurrence and rapid progress of periodontitis.

Synthesis and pharmacological evaluation of novel N-Mannich bases derived from 5,5-diphenyl and 5,5-di(propan-2-yl)imidazolidine-2,4-dione core.

The aim of this study was to design and synthesize two series of N-Mannich bases with imidazolidine-2,4-dione core as a potential anticonvulsant with reduced toxicity and broad antiseizure activity. Preliminary screening revealed that the majority of synthesized compounds were effective in the maximal electroshock seizure (MES) and/or subcutaneous pentylenetetrazole (scPTZ) test. The most active in vivo compound, 18 (3-((4-methylpiperazin-1-yl)methyl)-5,5-diphenylimidazolidine-2,4-dione), exhibited an ED50 value comparable to that of phenytoin in the MES test (38.5 mg/kg vs 28.1 mg/kg), and more importantly, it showed four times higher potency than phenytoin in the 6 Hz test (12.2 mg/kg vs > 60 mg/kg). Additionally, 18 exhibited antiallodynic properties in the von Frey test in neuropathic (oxaliplatin-treated) mice. Compound 18 also demonstrated a broader spectrum of anticonvulsant activity than phenytoin and showed statistically significant antinociceptive properties in selected models of chronic pain.

Synthesis and Anticonvulsant Properties of New 3,3-Diphenyl-2,5-dioxo-pyrrolidin-1-yl-acetamides and 3,3-Diphenyl-propionamides.

The focused library of new amides derived from 3,3-diphenyl-2,5-dioxo-pyrrolidin-1-yl-acetic acid (2a-t) and 3,3-diphenyl-propionic acid (3a-t) as potential anticonvulsant agents was synthesized. The final products were obtained in the amidation reaction of the given carboxylic acid (2, 3) with appropriate secondary amines in the presence of carbonyldiimidazole (CDI) as a coupling reagent. The initial anticonvulsant screening was performed in mice intraperitoneally (i.p.) using the "classical" maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models, whereas the acute neurological toxicity was determined applying the rotarod test. Additionally, several compounds were studied also in the 6-Hz seizures recognized as the animal model of human pharmacoresistant epilepsy. In this series, compound 3q displayed a broad spectrum of activity across the preclinical seizure models (ED50 MES = 31.64 mg/kg; ED50 scPTZ = 75.41 mg/kg, ED50 6-Hz (32 mA) = 38.15 mg/kg). Consequently, compound 3q revealed a wider spectrum of protection, higher activity or/and a better safety profile than the commonly used antiepileptic drugs such as phenytoin, ethosuximide, valproic acid, or/and levetiracetam. Notably, the in vitro studies showed that the most possible mechanism of action of 3q may be connected to the interaction with neuronal voltage-sensitive sodium channels (site 2). Other substances were active predominantly in the chemically induced seizures. The results of the current studies indicate that the presence of the pyrrolidine-2,5-dione ring is important but not indispensable for anticonvulsant activity.

Concentration of MMP-8 and IL-1ß in gingival crevicular fluid in patients with chronic and aggressive periodontitis.

Modern research confirms the role of inflammatory mediators in the pathomechanism of periodontal tissue destruction. The aim of the study was to determine concentrations of MMP-8 and IL-1ß in gingival crevicular fluid (GCF) in patients with advanced chronic and aggressive periodontitis. The authors measured the concentrations of the above inflammatory mediators in gingival crevicular fluid of deep pockets (PD ≥ 6 mm) and shallow pockets (PD 4-5 mm) in 33 patients with advanced chronic periodontitis and in 16 patients with aggressive periodontitis. The control group consisted of 16 individuals with healthy periodontium. In all patients levels of MMP-8 and IL-1ß in GCF were determined with the ELISA method. The study showed significantly higher concentrations of MMP-8 and IL-1ß in GCF of both deep and shallow pockets in patients with periodontitis compared to healthy subjects. No difference in concentrations of the tested mediators was observed with reference to diagnosis of aggressive periodontitis (AP) or chronic periodontitis (CP).

Synthesis, and anticonvulsant activity of new amides derived from 3-methyl- or 3-ethyl-3-methyl-2,5-dioxo-pyrrolidin-1-yl-acetic acids.

This paper describes the synthesis of the library of 22 new 3-methyl- and 3-ethyl-3-methyl-2,5-dioxo-pyrrolidin-1-yl-acetamides as potential anticonvulsant agents. The maximal electroshock (MES) and the subcutaneous pentylenetetrazole (scPTZ) seizure models were used for screening all the compounds. The 6 Hz model of pharmacoresistant limbic seizures was applied for studying selected derivatives. Six amides were chosen for pharmacological characterization of their antinociceptive activity in the formalin model of tonic pain as well as local anesthetic activity was assessed in mice. The pharmacological data indicate on the broad spectra of activity across the preclinical seizure models. Compounds 10 (ED50=32.08 mg/kg, MES test) and 9 (ED50=40.34 mg/kg, scPTZ test) demonstrated the highest potency. These compounds displayed considerably better safety profiles than clinically relevant antiepileptic drugs phenytoin, ethosuximide, or valproic acid. Several molecules showed antinociceptive and local anesthetic properties. The in vitro radioligand binding studies demonstrated that the influence on the sodium and calcium channels may be one of the essential mechanisms of action.

Elastase and metalloproteinase-9 concentrations in saliva in patients with chronic periodontitis.

Elastase and metalloproteinase-9 (MMP-9) are two of numerous proteolytic enzymes released by neutrophilic granulocytes in the course of periodontitis. The aim of the study was to determine the concentrations of elastase and MMP-9 in saliva in patients with chronic periodontitis compared to healthy individuals. The enzyme-linked immunosorbent assay method was employed to determine the concentrations of elastase and MMP-9 in saliva in patients with chronic periodontitis and with pocket depth (PD) ≥ 6 mm and PD < 6 mm, as well as in saliva of healthy individuals. Significantly higher concentrations of elastase and MMP-9 were observed in patients with periodontitis compared to healthy individuals (p < 0.01). Also a significant difference in elastase concentration in saliva was observed between the PD ≥ 4 mm and PD < 6 mm groups and between the PD ≥ 6 mm and control groups, and statistically significant differences in MMP-9 concentrations between the PD ≥ 6 mm and control groups. No statistically significant differences were observed between the PD < 6 mm and control groups for elastase concentrations in saliva as well as between the PD ≥ 6 mm and PD < 6 mm groups, and also between the PD < 6 mm and control groups for MMP-9 concentrations in saliva. Elastase and MMP-9 concentrations in saliva can be considered as biochemical indicators of severity of periodontitis.

Design, Synthesis and Biological Activity of New Amides Derived from 3-Benzhydryl and 3-sec-Butyl-2,5-dioxo-pyrrolidin-1-yl-acetic Acid.

The aim of this study was to design and synthesize two new series of pyrrolidine-2,5-dione-acetamides with a benzhydryl or sec-butyl group at position 3 as potential anticonvulsants. Their anticonvulsant activity was evaluated in standard animal models of epilepsy: the maximal electroshock (MES), the 6 Hz, and the subcutaneous pentylenetetrazole (scPTZ) tests. The in vivo studies revealed the most potent anticonvulsant activity for 15 (3-(sec-butyl)-1-(2-(4-(3-trifluoromethylphenyl)piperazin-1-yl)-2-oxoethyl)pyrrolidine-2,5-dione), with ED50 values of 80.38 mg/kg (MES) and 108.80 mg/kg (6 Hz). The plausible mechanism of action was assessed in in vitro binding assays, in which 15 interacted effectively with voltage-gated sodium (site 2) and L-type calcium channels at a concentration of 100 µM. Subsequently, the antinociceptive activity of compounds 7 and 15 was observed in the hot plate test of acute pain. Moreover, compounds 7, 11 and 15 demonstrated an analgesic effect in the formalin test of tonic pain. The hepatotoxic properties of the most effective compounds (7, 11 and 15) in HepG2 cells were also investigated.

Periodontal condition of mandibular incisors treated with modified Kazanjian vestibuloplasty compared to untreated sites: A prospective study.

BACKGROUND: A shallow vestibule, insufficient keratinized tissue width and pulling of marginal gingiva may be associated with gingival recession, plaque accumulation and gingivitis. Conventional techniques for treatment of gingival recession use autogenous or allogenic grafts. However, these methods result in soreness at the donor site and pose an economic burden, which may cause patients to withdraw from treatment. Alternative therapy is currently not available to treat such patients. OBJECTIVES: The aim of this study was to evaluate changes in periodontal tissue at the mandibular incisors after vestibuloplasty, focusing on functional improvement of the existing soft tissue with no grafting. MATERIAL AND METHODS: Thirty patients with a shallow vestibule, minimal keratinized tissue width (KTW; ≤1 mm), gingival recession (REC) and pulling of gingiva underwent modified Kazanjian vestibuloplasty were included into the test group, whereas 27 patients did not undergo any surgery (control group). The probing pocket depth (PPD), clinical attachment level (CAL), gingival recession depth (GRD), and KTW were assessed at baseline and 12 months post-surgery. RESULTS: The mean KTW, GRD and CAL values improved in the test group. A significant increase in mean KTW value (1.17 ±1.22 mm, p = 0.0406) was detected in the test group, while the control group showed a further reduction in mean KTW value (0.13 ±0.45 mm). The mean GRD value decreased from 2.09 ±1.78 mm to 1.22 ±1.46 mm (p = 0.0087) in the test group, whereas in controls the mean GRD value increased from 1.95 ±1.29 mm to 2.34 ±1.44 mm (p = 0.0164). The mean KTW value at 3, 6 and 12 months compared to baseline showed an increase in the test group, and the mean GRD and CAL values exhibited the potential to improve. CONCLUSIONS: Sites treated with vestibuloplasty showed increased KTW, improvement in the gingival margin and CAL gain, whereas untreated sites showed continuous deterioration of the evaluated parameters. Vestibuloplasty may be recommended for patients avoiding major surgery for which functional improvement in tissue alone would provide a sufficient therapeutic outcome.

The Effect of Lactobacillus salivarius SGL03 on Clinical and Microbiological Parameters in Periodontal Patients.

The destruction of periodontal tissues during periodontitis is the result of the immune-inflammatory reactions to the bacteria of dental biofilm. Probiotics may reduce dysbiosis by the modification of the dental microbiome, which can influence the immune-inflammatory mechanisms. The aim of this study was to estimate the clinical and microbiological parameters, before and after 30 days of application of the dietary supplement containing Lactobacillus salivarius SGL03 or placebo. The study was conducted in 51 patients with stage I or II periodontitis during the maintenance phase of treatment. The clinical parameters and the number of colony forming units (CFU) of bacteria in supragingival plaque were assessed before and after 30 days of the oral once daily administration of the dietary supplement in the form of suspension containing L. salivarius SGL03 or placebo. There were no changes in the PI scores between and within the groups. The value of BOP decreased in both groups. In the study group the significant reduction of the mean pocket depth was revealed (from 2.5 to 2.42, p = 0,027) but without the difference between the groups. There were no significant changes in the number of bacteria within the groups. In the control, but not the study group, positive correlations were observed between the clinical parameters (variables) and the number of bacteria. The use of the dietary supplement containing L. salivarius SGL03 may reduce pocket depth despite the lack of changes in other clinical parameters and the number of bacteria in supragingival plaque.

Analgesic and antiallodynic activity of novel anticonvulsant agents derived from 3-benzhydryl-pyrrolidine-2,5-dione in mouse models of nociceptive and neuropathic pain.

The objective of this study was to evaluate analgesic and antiallodynic activity of four new 3-benzhydryl-pyrrolidine-2,5-dione derivatives, which demonstrated previously anticonvulsant activity in the seizure tests in mice. Analgesic activity was examined in acute (the hot plate test), tonic (the formalin test), as well as neuropathic (the oxaliplatin-induced peripheral neuropathy) pain models in mice. Moreover, potential sedative properties and hepatotoxicity were evaluated. To establish the plausible mechanism of action, in vitro assays were carried out. All tested compounds RS 34, RS 37, RS 48, and RS 49, similarly to pregabalin, were active in the second phase of formalin test, a model of tonic pain. The most promising effect was observed for compounds RS 34, RS 48, and RS 49, which in a statistically significant way attenuated the nocifensive response at all tested doses 1, 10, and 30 mg/kg. Furthermore, all compounds at a dose of 30 mg/kg revealed antiallodynic activity in neuropathic pain related to chemotherapy-induced peripheral neuropathy in mice. In experimental tests on three compounds RS 34, RS 37 and RS 48 at active doses no sedative properties were registered. In the in vitro assay the selected molecule RS 34 did not induce cytotoxic effect on hepatoma cells. The binding and functional studies did not provide firm evidence on possible mechanism of action of these derivatives. In conclusion, the tested pyrrolidine-2,5-dione derivatives with antiseizure activity exerted also analgesic and antiallodynic effects in mouse models of pain.

The Immune Response in Periodontal Tissues.

The uniqueness of periodontal diseases is caused by several factors. This group of diseases is caused by numerous bacterial species formed in the dental biofilm, and one cannot distinguish the specific pathogen that is responsible for the disease initiation or progress (though Gram-negative anaerobic rods are associated with the advanced form of the disease). The disease is both infectious and inflammatory in its nature, and in the state of health there is always a subclinical level of inflammatory response, caused by the so-called harmless bacteria. Negligence in oral hygiene may result in maturation of the biofilm and trigger host response, manifesting clinically as gingivitis or-later and in susceptible subjects-as periodontitis. The article presents the contemporary knowledge of the inflammatory reaction occurring in tissues surrounding the tooth during periodontal inflammation. The most important mechanisms are described, together with implications for clinicists.

The effects of the initial treatment phase and of adjunctive low-dose doxycycline therapy on clinical parameters and MMP-8, MMP-9, and TIMP-1 levels in the saliva and peripheral blood of patients with chronic periodontitis.

INTRODUCTION: The treatment of periodontal disease can consist of bacterial plaque reduction, risk factor elimination, and metalloproteinase inhibitor medication. The level of matrix metalloproteinases (MMPs) are regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs) as well as therapeutic low-dose doxycycline. The aim of the study was to evaluate the effect of the initial phase of periodontal treatment and the effect of doxycycline on clinical parameters and the MMP-8, MMP-9, and TIMP-1 concentrations in the saliva and peripheral blood of patients with chronic periodontitis. MATERIALS AND METHODS: The study group consisted of 33 patients with chronic periodontitis. Conventional periodontal treatment (scaling and root planing) was conducted on all the patients and doxycycline (20 mg orally) was administered twice daily for three months. Thirty-three controls received the conventional treatment only. Clinical scores (PI, BI, PD, CAL) were recorded before and three months after the treatment. MMP-8, MMP-9, and TIMP-1 concentrations in saliva and peripheral blood were measured by ELISA before and after the treatment of 20 patients from the study group and 13 of the controls. RESULTS: The application of doxycycline 20 mg resulted in significant improvement in clinical parameters compared with the conventional periodontal treatment. Doxycycline did not produce significant reductions in MMP-8 and MMP-9 levels in saliva observed after the conventional treatment. The study revealed increases in the TIMP-1 concentration and the MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios in saliva and blood after treatment with doxycycline. CONCLUSIONS: The study confirmed the modulating effect of doxycycline on the host response in chronic periodontitis.