Characterization of the release profile of doxycycline by PLGA microspheres adjunct to non-surgical periodontal therapy

The aim of this pilot study was to assess the release of locally delivered doxycycline by poly (l-lactide-co-glycolide) (PLGA) microspheres in the periodontal pocket of patients with chronic periodontitis, treated by non-surgical periodontal therapy. Nineteen sites of non-adjacent teeth of four different patients were evaluated. Five milligram of PLGA microspheres loaded with 16 doxycycline hyclate (DOX) was administered per periodontal site. To quantify DOX released into the periodontal pocket, gingival crevicular fluid (GCF) was collected from the sites on days 2, 5, 7, 10, 15, and 20 after DOX application, and high-performance liquid chromatography was performed. Data were statistically assessed by ANOVA/Tukey test. At days 2, 5, and 7, the DOX concentration was stably sustained (23.33 ± 1.38, 23.4 ± 1.82, and 22.75 ± 1.33 μg/mL, respectively), with no significant differences over these assessment times (p > 0.05). At days 10 and 15, a tendency was observed toward a decrease in DOX concentration (21.74 ± 0.91 and 20.53 ± 4.88 μg/mL, respectively), but a significant decrease in GCF drug concentration (19.69 ± 4.70 μg/mL) was observed only on day 20. The DOX delivery system developed demonstrated a successful sustained release after local administration, as an adjunct to non-surgical periodontal therapy.     

Trends in drug resistance, serotypes, and molecular types of Streptococcus pneumoniae colonizing preschool-age children attending day care centers in Lisbon, Portugal: a summary of 4 years of annual surveillance

Of the nasopharyngeal cultures recovered from 942 day care center (DCC) attendees in Lisbon, Portugal, 591 (62%) yielded Streptococcus pneumoniae during a surveillance performed in February and March of 1999. Forty percent of the isolates were resistant to one or more antimicrobial agents. In particular, 2% were penicillin resistant and 20% had intermediate penicillin resistance. Multidrug resistance to macrolides, lincosamides, and tetracycline was the most frequent antibiotype (17% of all isolates). Serotyping and molecular typing by pulsed-field gel electrophoresis were performed for 202 out of 237 drug-resistant pneumococci (DRPn). The most frequent serotypes were 6B (26%), 14 (22%), 19F (16%), 23F (10%), and nontypeable (12%). The majority (67%) of the DRPn strains were representatives of nine international clones included in the Pneumococcal Molecular Epidemiology Network; eight of them had been detected in previous studies. Fourteen novel clones were identified, corresponding to 26% of the DRPn strains. The remaining 7% of the strains were local clones detected in our previous studies. Comparison with studies conducted since 1996 in Portuguese DCCs identified several trends: (i) the rate of DRPn frequency has fluctuated between 40 and 50%; (ii) the serotypes most frequently recovered have remained the same; (iii) nontypeable strains appear to be increasing in frequency; and (iv) a clone of serotype 33F emerged in 1999. Together, our observations highlight that the nasopharynxes of children in DCCs are a melting pot of successful DRPn clones that are important to study and monitor if we aim to gain a better understanding on the epidemiology of this pathogen.     

Clinical significance of elevated alanine aminotransferase in blood donors: a follow-up study.

Alanine aminotransferase (ALT) elevation in blood donors can be related to many variables such as viral hepatitis, overweight and ethanol consumption. BACKGROUND/AIMS: This study aims to define factors associated with ALT elevation in candidates for blood donation, to evaluate ALT levels during follow-up, and to establish a histological diagnosis of hepatic disease. METHODS: Alcoholism, obesity, drug-induced liver disease, diabetes, hemochromatosis and alpha 1-anti-trypsin deficiency were investigated in 119 subjects (113 males, six females, aged 33.4+/-8.4 years) who were hepatitis B surface antigen/anti-hepatitis C virus negative and had been rejected as blood donors as a result of elevated ALT (>1.5 times the upper normal limit (UNL) in two determinations). During follow-up, ALT was determined every 8 weeks and liver biopsy recommended in cases with persistently elevated ALT levels. RESULTS: Obesity (30.2%) and alcoholism (28.6%) were most frequently associated with ALT elevation and in 9.2% of cases no association was found. ALT levels decreased significantly, regardless of the associated factor. Liver histology in 40 patients showed steatosis (35%), steatohepatitis (30%), non-specific reactive hepatitis (12.5% of cases), normal liver (15% of cases) and alcoholic cirrhosis, hemochromatosis and non-specific portal fibrosis in three cases. CONCLUSION: ALT levels usually dropped during follow-up and although severe hepatic lesions can be found in asymptomatic blood donors, mild hepatic damage is the rule.     

Biological therapy in rheumatoid vasculitis: a systematic review

Clinical Rheumatology - Rheumatoid vasculitis (RV) is one of the most severe extra-articular manifestations of rheumatoid arthritis, with significant morbidity and mortality, requiring aggressive...     

Anti-atherogenic and anti-inflammatory properties of high-density lipoprotein are affected by specific antibodies in systemic lupus erythematosus

Objective. To determine whether antibodies against high-densitylipoprotein (aHDL) and apolipoprotein A-I (aApo A-I) interferewith the anti-atherogenic functions of high-density lipoprotein(HDL) and relate to disease activity and damage in SLE. Methods. Seventy-seven SLE patients were compared with an age-and sex-frequency matched control group. Immunoglobulin G (IgG)aHDL, IgG aApoA-I, soluble vascular cell and intracellular celladhesion molecules (VCAM-1 and ICAM-1, respectively) were measuredby ELISA, paraoxonase (PON) activity by spectrophotometry, nitricoxide (NOx) metabolites by the Griess reaction, and total anti-oxidantcapacity (TAC) by chemiluminescence. Results. Compared with controls, SLE patients showed highertitres of IgG aHDL (P < 0.0001) and IgG aApo A-I (P <0.0001), lower PON activity (P < 0.0001), increased NOx (P< 0.0001), VCAM-1 (P < 0.0001) and ICAM-1 (P = 0.0008)and lower TAC (P = 0.0006). Titres of IgG aHDL positively correlatedwith IgG aApo A-I (r = 0.64, P < 0.0001), NOx (r = 0.32,P = 0.007), inversely correlated with PON activity (r = –0.34,P = 0.002) and TAC (r = –0.43, P = 0.0004) and were independentlyassociated with ICAM-1 (t = 3.509, P = 0.001). IgG aApo A-Ititres correlated positively with NO (r = 0.37, P = 0.007),inversely with PON activity (r = –0.31, P = 0.006), TAC(r = –0.47, P < 0.0001) and were independently associatedwith HDL (t = –2.747, P = 0.008) and VCAM-1 (t = 3.311,P = 0.002), the latter alongside NOx (T = 2.271, P = 0.02).Elevated titres of IgG aHDL and IgG aApo A-I and reduced PONactivity related to increased disease score (BILAG) and damageindex (SLICC/ACR DI). Conclusion. In SLE, IgG aHDL and aApo A-I associate with diseaseactivity and damage and interfere with the anti-oxidant andanti-inflammatory functions of HDL favouring atherogenesis. KEY WORDS: Systemic lupus, Antibodies against high-density lipoprotein, Antibodies against Apolipoprotein A-I, Paraoxonase, Nitric oxide, Endothelial dysfunction Submitted 6 March 2008; revised version accepted 15 September 2008.     

Lactase persistence/non-persistence variants, C/T_13910 and G/A_22018, as a diagnostic tool for lactose intolerance in IBS patients

BACKGROUND: Irritable bowel syndrome (IBS) is a symptom-based disorder characterized by abdominal pain related to altered bowel habit. We evaluated the predictive power of 2 genetic markers of hypolactasia, C/T_13910 and G/A_22018, in IBS patients with and without lactose intolerance in order to gain insight into the role of lactose intolerance in IBS. METHODS: Seventy five patients (59F/16M, mean age: 49.6+/-14.2 years) with an IBS diagnosis based on Rome II criteria and 272 healthy individuals, where 74 (58F/16M, 54.1+/-10.9 years) were matched-controls, were evaluated. IBS and healthy individuals were genotyped for the C/T_13910 and G/A_22018 polymorphisms nearby the lactase-phlorizin hydrolase gene. Hydrogen breath test (HBT) with gas chromatography was performed in IBS patients to assess for lactose intolerance. RESULTS: Of the 75 IBS patients, 28 (37%) were defined as lactose intolerants. The grade/severity of symptoms after an oral lactose load were positively correlated to the expiratory H2 excretion (P<0.001). Alleles and genotypes frequencies from C/T_13910 and G/A_22018 were not significantly different between IBS patients and control individuals (P>0.05;NS). Presence of the C and G allele were positively associated with a higher expiratory hydrogen excretion and more intense gastrointestinal symptoms (P<0.001). Considering these polymorphisms as a diagnostic test for lactose intolerance in IBS patients, presence of the CC and GG genotypes were estimated to have, a sensitivity of 100% and 96%, respectively; and a specificity of 83% and 79%, positive predictive value of 76% and 73%, and negative predictive value of 100% and 97%. CONCLUSIONS: In IBS patients, genotyping of C/T_13910 and G/A_22018 polymorphisms predicts gastrointestinal symptoms after lactose ingestion and are a diagnostic tool for lactose intolerance.     

Caspofungin in vitro and in vivo activity against Brazilian Pythium insidiosum strains isolated from animals

OBJECTIVES: The present study evaluated the susceptibility of 27 clinical isolates of Pythium insidiosum to caspofungin in vitro and correlated the results with the therapeutic response in vivo in rabbits with experimental pythiosis. METHODS: The macrodilution method was performed in accordance with the CLSI document M38-A technique. Three reading criteria for MICs were adopted: MIC0, MIC1 and MIC2 (100%, 90% and 50% growth inhibition, respectively). The minimum fungicidal concentration was also determined. Ten rabbits inoculated with viable P. insidiosum zoospores were divided into two groups: group 1 (control) and group 2 (treated with caspofungin at a dosage of 1 mg/kg/day for 20 consecutive days). RESULTS: Of the isolates 51.8% had an MIC0 of 64 mg/L, 88.8% of isolates had an MIC1 between 8 and 64 mg/L and 62.9% of isolates had a minimum fungicidal concentration of 64 mg/L. In the in vivo assay, growth of subcutaneous lesions reduced during treatment, but rapidly resumed when treatment was stopped. CONCLUSIONS: The results showed that caspofungin has limited fungistatic activity against P. insidiosum. This work is the first study to analyse the susceptibility of this oomycete to inhibitors of beta-glucans of the cellular wall.