Infants tailor their attention to maximize learning.

Infants' remarkable learning abilities allow them to rapidly acquire many complex skills. It has been suggested that infants achieve this learning by optimally allocating their attention to relevant stimuli in the environment, but the underlying mechanisms remain poorly understood. Here, we modeled infants' looking behavior during a learning task through an ideal learner that quantified the informational structure of environmental stimuli. We show that saccadic latencies, looking time, and time spent engaged with a stimulus sequence are explained by the properties of the learning environments, including the level of surprise of the stimulus, overall predictability of the environment, and progress in learning the environmental structure. These findings reveal the factors that shape infants' advanced learning, emphasizing their predisposition to seek out stimuli that maximize learning.

TNFα deficiency results in increased IL-1ß in an early onset of spontaneous murine colitis.

Inflammatory bowel disease (Crohn's disease (CD) and ulcerative colitis (UC)) is a multifactorial disease resulting from immune dysregulation in the gut. The underlying colitis is characterized by high levels of inflammatory cytokines, including TNFα. Biological intervention for IBD patients using anti-TNFα antibodies is often an effective therapeutic solution. However, TNFα neutralization fails to induce remission in a subgroup of IBD patients, primarily in UC patients. There is a dearth of suitable animal models representing TNFα non-responders. Here we have combined one of the best UC models currently available, namely Winnie and the TNFαKO mouse to generate a TNFα-deficient Winnie to study early onset colitis. The induced TNFα deficiency with underlying colitis does not influence general health (viability and body weight) or clinical parameters (colon weight, colon length and histological colitis) when compared with the Winnie genotype alone. The molecular characterization resulted in identification of Il1ß as the major elevated cytokine during early phases of colitis. Further, in vitro functional assay using bone marrow-derived dendritic cells confirmed IL-1ß as the major cytokine released in the absence of TNFα. This study has generated a successful model of colitis that remains TNFα non-responsive and has demonstrated that IL-1ß expression is a major pathway for the progression of colitis in this system. These data also suggest that IL-1ß can be a potential target for clinical intervention of UC patients who fail to respond to TNFα neutralization.

Multiple rare genetic variants co-segregating with familial IgA nephropathy all act within a single immune-related network.

BACKGROUND: IgA nephropathy (IgAN) is a common complex disease with a strong genetic involvement. We aimed to identify novel, rare, highly penetrant risk variants combining family-based linkage analysis with whole-exome sequencing (WES). METHODS: Linkage analysis of 16 kindreds of South Italian ancestry was performed using an 'affected-only' strategy. Eight most informative trios composed of two familial cases and an intrafamilial control were selected for WES. High-priority variants in linked regions were identified and validated using Sanger sequencing. Custom TaqMan assays were designed and carried out in the 16 kindreds and an independent cohort of 240 IgAN patients and 113 control subjects. RESULTS: We found suggestive linkage signals in 12 loci. After sequential filtering and validation of WES data, we identified 24 private or extremely rare (MAF <0.0003) linked variants segregating with IgAN status. These were present within coding or regulatory regions of 23 genes that merged into a common functional network. The genes were interconnected by AKT, CTNNB1, NFKB, MYC and UBC, key modulators of WNT/ß-catenin and PI3K/Akt pathways, which are implicated in IgAN pathogenesis. Overlaying publicly available expression data, genes/proteins with expression notably altered in IgAN were included in this immune-related network. In particular, the network included the glucocorticoid receptor gene, NR3C1, which is the target of corticosteroid therapy routinely used in the treatment of IgAN. CONCLUSION: Our findings suggest that disease susceptibility could be influenced by multiple rare variants acting in a common network that could provide the starting point for the identification of potential drug targets for personalized therapy.

MicroRNAs in kidney diseases: new promising biomarkers for diagnosis and monitoring.

A series of microRNAs (miRNAs) have a critical role in many cellular and physiological activities such as cell cycle, growth, proliferation, apoptosis and metabolism. miRNAs are also important in the maintenance of renal homeostasis and kidney diseases. In vitro and in vivo animal models have shown a critical role of miRNAs in the development of diabetic nephropathy (DN) and in the progression of renal fibrosis. Specific miRNAs in renal tissue and peripheral blood mononuclear cells (PBMCs) are up and downregulated in different kidney diseases. They represent new potential biomarkers for diagnosis and targeted therapy. In addition, urinary miRNAs may be considered non-invasive biomarkers for monitoring the progression of renal damage. The activity of miRNAs can be modified by different approaches such as the use of antisense oligonucleotide inhibitors (antagomirs), tandem miRNA-binding site repeats manufactured by Decoy or Sponge technologies and miRNA mimics. The use of miRNA blockers or antagonists as therapeutic agents is very attractive but new information will be necessary considering their role in other systems.

[Pulmonary arterial hypertension in adult patients with congenital heart disease]. / Ipertensione arteriosa polmonare nei pazienti adulti con cardiopatia congenita.

Pulmonary Hypertension (PH) is definited by a mean pulmonary artery pressure (PAPm) >25 mmHg at rest. The Dana Point 2008 Revised Classification System represents the most recent classification system update with respect of various etiologies of PH. About 10 % of adolescents or adults with uncorrected congenital heart disease (CHD) with left-to-right shunt and high pulmonary blood flow develop Pulmonary Arterial Hypertension (PAH) . Progressive vascular remodeling and increase in pulmonary vascular resistance (PVR) may ultimately lead to reversal of the shunt (pulmonary to systemic) causing cyanosis and determining the so-called Eisenmenger Syndrome (ES). Recent advances in the early diagnosis and medical targeted treatment of adult patients with CHD-PAH and ES can improve PAP, PVR and exercise tolerance, together with NYHA Class and survival, and may potentially reverse the vascular remodeling process in selected patients.

Atypical esophageal vascular lesions observed in liver cirrhosis.

Chronic liver disease is known to be associated with several vascular alterations including portal hypertension and hepato-pulmonary insufficiency. We report a case of esophageal vascular lesions resembling spider naevi in a patient with nonalcoholic cirrhosis who underwent an upper gastrointestinal (GI) endoscopy. We observed the presence of multiple white round elevations, 5-6 mm in size, with radiating thin-walled vessels, in the middle and distal esophagus. The histological examination documented the presence of multiple dilated blood vessels in the mucosal layer of the esophagus, with striking thickening of the endothelium wall. There was no evidence of esophagogastric varices, but only of a moderate congestive antral gastropathy. To our knowledge, these endoscopic esophageal findings have not yet been described in cirrhosis.

[Thrombosis and cardiovascular diseases]. / Trombosi e malattie cardiovascolari.

Thrombosis represents the propensity toward arterial and/or venous thrombotic events. Many causes of thrombosis are now known: clinical predisposing factors (recent major surgery, varices of lower limbs, prolonged bedrittening); immunological, hematological and liver diseases; inborn or acquired coagulation factors' or plasmatic proteins' deficiency; platelets disfunction. Thrombotic screening of affected individuals is fundamental to adjust dosage and length of therapy, for secondary prevention and for relatives evaluation.

Molecular characterization of subunit 6 of the COP9 signalosome and its role in multifaceted developmental processes in Arabidopsis.

The COP9 signalosome is a highly conserved protein complex initially identified as a repressor of photomorphogenesis. Here, we report that subunit 6 of the Arabidopsis COP9 signalosome is encoded by a family of two genes (CSN6A and CSN6B) located on chromosomes V and IV, respectively. The CSN6A and CSN6B proteins share 87% amino acid identity and contain a MPR1p and PAD1p N-terminal (MPN) domain at the N-terminal region. The CSN6 proteins share homology with CSN5 and belong to the Mov34 superfamily of proteins. CSN6 proteins present only in the complex form and coimmunoprecipitate with other known subunits of the COP9 signalosome. Partial loss-of-function strains of the COP9 signalosome created by antisense and cosuppression with CSN6A exhibit diverse developmental defects, including homeotic organ transformation, symmetric body organization, and organ boundary definition. Protein blot analysis revealed that the defective plants accumulate significant amounts of ubiquitinated proteins, supporting the conclusion that the COP9 signalosome regulates multifaceted developmental processes through its involvement in ubiquitin/proteasome-mediated protein degradation.

Initial outcome and long-term effect of surgical and non-surgical treatment of advanced periodontal disease.

AIM: A clinical trial was performed to determine (i) the initial outcome of non-surgical and surgical access treatment in subjects with advanced periodontal disease and (ii) the incidence of recurrent disease during 12 years of maintenance following active therapy. MATERIAL AND METHODS: Each of the 64 subjects included in the trial showed signs of (i) generalized gingival inflammation, (ii) had a minimum of 12 non-molar teeth with deep pockets (> or =6 mm) and with > or =6 mm alveolar bone loss. They were randomly assigned to 2 treatment groups; one surgical (SU) and one non-surgical (SRP). Following a baseline examination, all patients were given a detailed case presentation which included oral hygiene instruction. The subjects in SU received surgical access therapy, while in SRP non-surgical treatment was provided. After this basic therapy, all subjects were enrolled in a maintenance care program and were provided with meticulous supportive periodontal therapy (SPT) 3-4 times per year. Sites that at a recall appointment bled on gentle probing and had a PPD value of > or =5 mm were exposed to renewed subgingival instrumentation. Comprehensive re-examinations were performed after 1, 3, 5 and 13 years of SPT. If a subject between annual examinations exhibited marked disease progression (i.e., additional PAL loss of > or =2 mm at > or =4 teeth), he/she was exited from the study and given additional treatment. RESULTS: It was observed that (i) surgical therapy (SU) was more effective than non-surgical scaling and root planing (SRP) in reducing the overall mean probing pocket depth and in eliminating deep pockets, (ii) more SRP-treated subjects exhibited signs of advanced disease progression in the 1-3 year period following active therapy than SU-treated subjects. CONCLUSION: In subjects with advanced periodontal disease, surgical therapy provides better short and long-term periodontal pocket reduction and may lead to fewer subjects requiring additional adjunctive therapy.

A role of Arabidopsis COP9 signalosome in multifaceted developmental processes revealed by the characterization of its subunit 3.

The COP9 signalosome is a highly conserved eight-subunit protein complex initially defined as a repressor of photomorphogenic development in Arabidopsis. It has recently been suggested that the COP9 signalosome directly interacts and regulates SCF type E3 ligases, implying a key role in ubiquitin-proteasome mediated protein degradation. We report that Arabidopsis FUS11 gene encodes the subunit 3 of the COP9 signalosome (CSN3). The fus11 mutant is defective in the COP9 signalosome and accumulates significant amount of multi-ubiquitinated proteins. The same mutant is specifically impaired in the 26S proteasome-mediated degradation of HY5 but not PHYA, indicating a selective involvement in protein degradation. Reduction-of-function transgenic lines of CSN3 produced through gene co-suppression also accumulate multi-ubiquitinated proteins and exhibit diverse developmental defects. This result substantiates a hypothesis that the COP9 signalosome is involved in multifaceted developmental processes through regulating proteasome-mediated protein degradation.

Interactions of the COP9 signalosome with the E3 ubiquitin ligase SCFTIRI in mediating auxin response.

The COP9 signalosome is an evolutionary conserved multiprotein complex of unknown function that acts as a negative regulator of photomorphogenic seedling development in Arabidopsis. Here, we show that plants with reduced COP9 signalosome levels had decreased auxin response similar to loss-of-function mutants of the E3 ubiquitin ligase SCFTIR1. Furthermore, we found that the COP9 signalosome and SCFTIR1 interacted in vivo and that the COP9 signalosome was required for efficient degradation of PSIAA6, a candidate substrate of SCFTIR1. Thus, the COP9 signalosome may play an important role in mediating E3 ubiquitin ligase-mediated responses.

Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome.

SCF ubiquitin ligases control various processes by marking regulatory proteins for ubiquitin-dependent proteolysis. To illuminate how SCF complexes are regulated, we sought proteins that interact with the human SCF component CUL1. The COP9 signalosome (CSN), a suppressor of plant photomorphogenesis, associated with multiple cullins and promoted cleavage of the ubiquitin-like protein NEDD8 from Schizosaccharomyces pombe CUL1 in vivo and in vitro. Multiple NEDD8-modified proteins uniquely accumulated in CSN-deficient S. pombe cells. We propose that the broad spectrum of activities previously attributed to CSN subunits--including repression of photomorphogenesis, activation of JUN, and activation of p27 nuclear export--underscores the importance of dynamic cycles of NEDD8 attachment and removal in biological regulation.

The effect of systemic antibiotics in the treatment of patients with recurrent periodontitis.

BACKGROUND: Subjects with periodontal disease exist who either (i) respond poorly to initial mechanical therapy ("refractory" periodontitis) or (ii) fail to adopt adequate self-performed plaque control techniques and hence develop recurrent disease ("recurrent" periodontitis) at multiple sites during the supportive treatment phase (SPT). Various systemic antibiotic regimens have been tried as adjuncts to the mechanical (re-) treatment of such "difficult to treat"-patients. While most studies indicated a positive outcome of the adjunctive therapy, some clinical investigators reported that this additional measure provided little or no benefit. AIM: The aim of the present investigation was to study the more long term effect of adjunctive antibiotic therapy in the re-treatment of patients with a well defined history of recurrent periodontitis. MATERIAL AND METHODS: 17 subjects with recurrent advanced periodontal disease were, following a baseline examination, subjected to non-surgical therapy including the use of systemic antibiotics (amoxicillin and metronidazole). They were placed in a careful SPT program and re-examined after 1, 3 and 5 years. The examinations included both clinical and microbiological assessments. RESULTS: It was demonstrated that in subjects with advanced and recurrent periodontitis, re-treatment including (i) comprehensive scaling and root planing (SRP), (ii) systemic administration of antibiotics and (iii) meticulous supragingival plaque control by both mechanical and chemical means established periodontal conditions that in the short term (3 years) and in the majority of subjects could be properly maintained by traditional SPT measures. Between 3 and 5 years, however, only 5 of the 17 subjects exhibited stable periodontal attachment levels. CONCLUSIONS: Some deep pockets and furcations were most likely inadequately instrumented during the active treatment phase. Microorganisms residing in biofilms left in such locations were probably not sufficiently affected by the 2 weeks of adjunctive antibiotic therapy. It is suggested that removal of certain subgingival deposits, therefore, may require surgical intervention.

The long-term effect of systemic tetracycline used as an adjunct to non-surgical treatment of advanced periodontitis.

AIM: In the present study both the short- and the long-term effects were evaluated of a treatment that, during the phase of basic therapy, included administration of systemic tetracycline and non-surgical intervention. MATERIAL AND METHODS: 35 adult human subjects with advanced periodontitis, 19 females and 16 males, aged between 24 and 60 years, were included in a test group. 80 age- and sex-matched adult periodontitis subjects were recruited for a control group (42 females and 38 males). A baseline examination included assessment of the following parameters: number of teeth, plaque, bleeding on probing, probing attachment level, probing pocket depth. In radiographs, the distance between the cemento-enamel junction and the alveolar bone crest was determined at all interproximal sites. The subjects were given oral hygiene instruction. The members of the test group were provided with tablets with 250 mg of tetracycline hydrochloride and were instructed to take 1 tablet 4x per day for a period of 3 weeks. No antibiotic was given to the subjects in the control group. During the 3-week interval, all participants received 4-6 sessions of non-surgical periodontal therapy. All subjects were subsequently enrolled in a maintenance care program and were provided with supportive periodontal therapy (SPT) 3-4x per year. Clinical re-examinations were performed after 1, 3, 5 and 13 years. RESULTS: The present investigation demonstrated that tetracycline administered during a 3-week period concomitant with non-surgical treatment enhanced the outcome of mechanical therapy. At the re-examination 1 year after active therapy, there was in the test group an average gain in probing attachment that was almost 3x higher than the gain that occurred in an age and sex matched Control group. Re-examinations after 3, 5, and 13 years of SPT disclosed that this short-term benefit was not maintained in the longer perspective. CONCLUSION: The beneficial effect of systemically administered tetracycline on probing attachment level occurred in the first year post-therapy. Annual rates of probing attachment level change from 1 to 13 years did not differ between groups.

Longitudinal periodontal tissue alterations during supportive therapy. Findings from subjects with normal and high susceptibility to periodontal disease.

AIM: The aim of the study was to evaluate disease progression during supportive periodontal therapy in (i) a group of 225 subjects with "normal" (NG) and (ii) a group with high susceptibility (HSG; n= 109) to periodontal disease (based on their baseline disease status). MATERIAL AND METHODS: The following variables were recorded at the baseline examination (1 year after they received non-surgical periodontal therapy) and at the re-examination after 12 years of maintenance: number of teeth, plaque, probing pocket depth, probing attachment level, bone level in full mouth radiographs. All assessments were performed in a standardized manner and by well-trained and calibrated examiners. Supportive periodontal therapy was delivered 3-4 x per year and included repeated oral hygiene instruction and debridement. In addition, sites that bled on probing and had a PPD value of > or = 5 mm received subgingival instrumentation. RESULTS: A comparison between the findings at baseline and after 12 years revealed that in the NG, most subjects maintained their periodontal condition unchanged during the maintenance period; only a few subjects experienced tooth loss and the figures describing the mean amount of bone and attachment loss were small (0.5 mm and 0.3 mm respectively). The HSG patients experienced some tooth loss and also lost significant amounts of bone and attachment during the 12 years of SPT. Thus, in this group of subjects, the mean overall PAL loss amounted to 0.8 mm, i.e., 0.06 mm/tooth surface/year. In the NG, the overall attachment loss was significantly smaller: 0.5 mm, i.e. 0.04 mm/tooth surface/year. CONCLUSION: In subjects with a high susceptibility for periodontal disease who had been treated for this condition by non-surgical means, an SPT program including regularly repeated oral hygiene instruction and subgingival debridement, made it possible to maintain bone and attachment levels at a reasonably stable level over a 12-year period. A similar SPT provided to a group of subjects with normal susceptibility to periodontal disease, on the other hand, prevented almost entirely major tooth, bone and attachment loss.

The cellular level of PR500, a protein complex related to the 19S regulatory particle of the proteasome, is regulated in response to stresses in plants.

In Arabidopsis seedlings and cauliflower florets, Rpn6 (a proteasome non-ATPase regulatory subunit) was found in two distinct protein complexes of approximately 800 and 500 kDa, respectively. The large complex likely represents the proteasome 19S regulator particle (RP) because it displays the expected subunit composition and all characteristics. The small complex, designated PR500, shares at least three subunits with the "lid" subcomplex of 19S RP and is loosely associated with an hsp70 protein. In Arabidopsis COP9 signalosome mutants, PR500 was specifically absent or reduced to an extent that correlates with the severity of the mutations. Furthermore, PR500 was also diminished in response to potential protein-misfolding stresses caused by the heat shock and canavanine treatment. Immunofluorescence studies suggest that PR500 has a distinct localization pattern and is enriched in specific nuclear foci. We propose that PR500 may be evolved in higher plants to cope with the frequently encountered environmental stresses.

Arabidopsis cop8 and fus4 mutations define the same gene that encodes subunit 4 of the COP9 signalosome.

The pleiotropic constitutive photomorphogenic/deetiolated/fusca (cop/det/fus) mutants of Arabidopsis exhibit features of light-grown seedlings when grown in the dark. Cloning and biochemical analysis of COP9 have revealed that it is a component of a multiprotein complex, the COP9 signalosome (previously known as the COP9 complex). Here, we compare the immunoaffinity and the biochemical purification of the COP9 signalosome from cauliflower and confirm its eight-subunit composition. Molecular cloning of subunit 4 of the complex revealed that it is a proteasome-COP9 complex-eIF3 domain protein encoded by a gene that maps to chromosome 5, near the chromosomal location of the cop8 and fus4 mutations. Genetic complementation tests showed that the cop8 and fus4 mutations define the same locus, now designated as COP8. Molecular analysis of the subunit 4-encoding gene in both cop8 and fus4 mutants identified specific molecular lesions, and overexpression of the subunit 4 cDNA in a cop8 mutant background resulted in complete rescue of the mutant phenotype. Thus, we conclude that COP8 encodes subunit 4 of the COP9 signalosome. Examination of possible molecular interactions by using the yeast two-hybrid assay indicated that COP8 is capable of strong self-association as well as interaction with COP9, FUS6/COP11, FUS5, and Arabidopsis JAB1 homolog 1, the latter four proteins being previously defined subunits of the Arabidopsis COP9 signalosome. A comparative sequence analysis indicated that COP8 is highly conserved among multicellular eukaryotes and is also similar to a subunit of the 19S regulatory particle of the 26S proteasome.

RNA polymerase subunits encoded by the plastid rpo genes are not shared with the nucleus-encoded plastid enzyme.

Plastid genes in photosynthetic higher plants are transcribed by at least two RNA polymerases. The plastid rpoA, rpoB, rpoC1, and rpoC2 genes encode subunits of the plastid-encoded plastid RNA polymerase (PEP), an Escherichia coli-like core enzyme. The second enzyme is referred to as the nucleus-encoded plastid RNA polymerase (NEP), since its subunits are assumed to be encoded in the nucleus. Promoters for NEP have been previously characterized in tobacco plants lacking PEP due to targeted deletion of rpoB (encoding the beta-subunit) from the plastid genome. To determine if NEP and PEP share any essential subunits, the rpoA, rpoC1, and rpoC2 genes encoding the PEP alpha-, beta'-, and beta"-subunits were removed by targeted gene deletion from the plastid genome. We report here that deletion of each of these genes yielded photosynthetically defective plants that lack PEP activity while maintaining transcription specificity from NEP promoters. Therefore, rpoA, rpoB, rpoC1, and rpoC2 encode PEP subunits that are not essential components of the NEP transcription machinery. Furthermore, our data indicate that no functional copy of rpoA, rpoB, rpoC1, or rpoC2 that could complement the deleted plastid rpo genes exists outside the plastids.

The COP9 complex is conserved between plants and mammals and is related to the 26S proteasome regulatory complex.

The COP9 complex, genetically identified in Arabidopsis as a repressor of photomorphogenesis, is composed of multiple subunits including COP9, FUS6 (also known as COP11) and the Arabidopsis JAB1 homolog 1 (AJH1) ([1-3]; unpublished observations). We have previously demonstrated the existence of the mammalian counterpart of the COP9 complex and purified the complex by conventional biochemical and immunoaffinity procedures [4]. Here, we report the molecular identities of all eight subunits of the mammalian COP9 complex. We show that the COP9 complex is highly conserved between mammals and higher plants, and probably among most multicellular eukaryotes. It is not present in the single-cell eukaryote Saccharomyces cerevisiae, however. All of the subunits of the COP9 complex contain structural features that are also present in the components of the proteasome regulatory complex and the translation initiation factor eIF3 complex. Six subunits of the COP9 complex have overall similarity with six distinct non-ATPase regulatory subunits of the 26S proteasome, suggesting that the COP9 complex and the proteasome regulatory complex are closely related in their evolutionary origin. Subunits of the COP9 complex include regulators of the Jun N-terminal kinase (JNK) and c-Jun, a nuclear hormone receptor binding protein and a cell-cycle regulator. This suggests that the COP9 complex is an important cellular regulator modulating multiple signaling pathways.

The use of metronidazole and amoxicillin in the treatment of advanced periodontal disease. A prospective, controlled clinical trial.

The present clinical trial was performed to study the effect of systemic administration of metronidazole and amoxicillin as an adjunct to mechanical therapy in patients with advanced periodontal disease. 16 individuals, 10 female and 6 male, aged 35-58 years, with advanced periodontal disease were recruited. A baseline examination included assessment of clinical, radiographical, microbiological and histopathological characteristics of periodontal disease. The 16 patients were randomly distributed into 2 different samples of 8 subjects each. One sample of subjects received during the first 2 weeks of active periodontal therapy, antibiotics administered via the systemic route (metronidazole and amoxicillin). During the corresponding period, the 2nd sample of subjects received a placebo drug (placebo sample). In each of the 16 patients, 2 quadrants (1 in the maxilla and 1 in the mandible) were exposed to non-surgical subgingival scaling and root planing. The contralateral quadrants were left without subgingival instrumentation. Thus, 4 different treatment groups were formed; group 1: antibiotic therapy but no scaling, group 2: antibiotic therapy plus scaling, group 3: placebo therapy but no scaling, group 4: placebo therapy plus scaling. Re-examinations regarding the clinical parameters were performed, samples of the subgingival microbiota harvested and 1 soft tissue biopsy from 1 scaled and 1 non-scaled quadrant obtained 2 months and 12 months after the completion of active therapy. The teeth included in groups 1 and 3 were following the 12-month examination exposed to non-surgical periodontal therapy, and subsequently exited from the study. Groups 2 and 4 were also re-examined 24 months after baseline. The findings demonstrated that in patients with advanced periodontal disease, systemic administration of metronidazole plus amoxicillin resulted in (i) an improvement of the periodontal conditions, (ii) elimination/suppression of putative periodontal pathogens such as A. actinomycetemcomitans, P. gingivalis, P. intermedia and (iii) reduction of the size of the inflammatory lesion. The antibiotic regimen alone, however, was less effective than mechanical therapy with respect to reduction of BoP - positive sites, probing pocket depth reduction, probing attachment gain. The combined mechanical and systemic antibiotic therapy (group 2) was more effective than mechanical therapy alone in terms of improvement of clinical and microbiological features of periodontal disease.