Biomedical subjects

Janet M Guthmiller

Publications and source records attributed to Janet M Guthmiller.

7 recordsLinked to original sources

PubMed2005

The nervous system and innate immunity: the neuropeptide connection.

Many neuropeptides and peptide hormones are very similar to antimicrobial peptides in their amino acid composition, amphipathic design, cationic charge and size. Their antimicrobial activities suggest they may also be directly involved in innate defense. Here we discuss recent advances in understanding how the mammalian nervous system, equipped with neuropeptides and peptide hormones with potent antimicrobial properties, might directly defend the host from microbial assault. As examples, we have chosen five well described, locally produced neuropeptides that may serve a previously unrecognized, direct antimicrobial, innate immune function in four anatomical sites.

Adrenomedullin↗

PubMed2005

Factors related to utilization of dental services during pregnancy.

OBJECTIVES: The purposes of this study were to investigate factors related to utilization of dental services during pregnancy and to assess the extent of mothers' knowledge regarding oral health during pregnancy and its effect on pregnancy outcomes. MATERIALS AND METHODS: Cross-sectional data were collected from 625 women using a structured questionnaire mailed to mothers who had given birth in Johnson County, Iowa from August 2001 to March 2002. The survey assessed knowledge, behaviours, attitudes toward dental care during pregnancy, and personal, demographic and pregnancy-related factors. Variables which showed associations in bivariate analysis (p< or =0.1) were considered as candidates for building logistic regression models separately by domain (demographics, dental health care behaviours, lifestyle, financial variables, pregnancy-related variables, and knowledge of the possible association between oral health and pregnancy). Significant domain-specific regression results (p< or =0.05) were used to develop a final model using forward stepwise logistic regression analyses. RESULTS: The overall response rate was 69%. Dental visits during pregnancy were reported by 49% of respondents. Forty-three percent were aware of the possible connection between oral health and pregnancy outcomes. In the final logistic regression analysis, factors significantly associated with reporting dental visits during pregnancy were: (1) personal factors (being married, greater frequency of visiting the dentist when not pregnant and use of inter-proximal cleaning aids); (2) financial factors (dental insurance); and (3) knowledge of the possible connection between oral health and pregnancy outcomes. CONCLUSIONS: There was limited knowledge of the possible relationships between oral health and pregnancy outcomes in a fairly homogeneous population of women who were of relatively high socioeconomic standing. This study suggests that better education of the importance of dental care before and during pregnancy is needed.

Adult↗

PubMed2004

Correlation between beta-defensin expression and induction profiles in gingival keratinocytes.

Human beta-defensins are antimicrobial peptides produced by epithelial cells. To date, 28 beta-defensins have been described and the expression of a select few has been classified as constitutive or inducible. Most studies have evaluated expression and regulation using a limited number of primary cell cultures or immortalized cell lines. The goal of this study was to quantitatively assess the in vitro expression and inducibility profiles of human beta-defensins, HBD-1, HBD-2, and HBD-3 across a number of primary gingival keratinocyte cultures. Cultured cells from 14 human subjects were stimulated with interleukin-1 beta (IL-1beta), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma) or Escherichia coli lipopolysaccharide (LPS) and analyzed by reverse transcription (RT)-PCR. A subset of cultures were quantitatively assessed by real-time PCR. HBD-1 presented the highest and most heterogeneous expression at the basal level (non-stimulated) as compared to expression of HBD-2 and HBD-3, which was significantly lower and homogeneous. IFN-gamma was a primary inducer for HBD-1 and HBD-3, while IL-1beta and TNF-alpha were primary inducers for HBD-2. Sporadic induction was seen for IL-2, IL-6 and LPS. Synergistic expression was seen when various cytokines were combined. Interestingly, the induction potential of each beta-defensin was directly correlated to its basal expression. An inhibitor of JAK2 kinase (Janus kinase), down-regulated IFN-gamma-induced HBD-1 and HBD-3 expression, suggesting a role for the JAK/signal transducer and activator of transcription (STAT) signaling pathway in their expression. HBD-2 protein expression of supernatants and cell lysates paralleled mRNA expression. The results suggest that beta-defensin expression and induction in gingival keratinocytes is similar to that seen in other tissue. However, the novel finding of considerable variation among induction levels and the correlation of the induction with basal expression suggests that these innate response elements may play a key role in susceptibility or resistance to disease in the oral cavity.

Anti-Infective Agents↗

PubMed2004

Expression of beta-defensins in gingival health and in periodontal disease.

BACKGROUND: Human beta-defensins (HBDs) are epithelial-derived antimicrobial peptides. The expression of three HBDs (HBD-1, HBD-2, and HBD-3) has been reported in oral mucosa, gingiva, and salivary glands. However, their role in protection against oral infections is not well understood. This study examined the expression of HBD-1, HBD-2, and HBD-3 mRNAs in gingival health and periodontal disease. METHODS: Gingival tissue discarded from periodontal procedures was obtained from 20 periodontally healthy and 29 periodontally diseased sites. Total RNA was isolated, and expression of beta-defensins was analyzed by both 35-cycle and semiquantitative (25-cycle) reverse transcription-polymerase chain reaction (RT-PCR). The level of expression was assigned ordinal scores of no expression, low expression, or high expression. mRNA expression was compared between healthy and diseased groups using exact tests of homogeneity and Cochran-Mantel-Haenszel tests; associations among the variables were assessed using exact tests and Kendall's tau-b statistic. RESULTS: All 49 samples demonstrated basal mRNA expression of HBD-1, HBD-2, and HBD-3. Significantly higher levels of HBD-3 (P = 0.012) expression were found in the healthy tissues as compared to the diseased ones. There was also a suggestion of higher expression of HBD-2 in the healthy tissues (P = 0.12). Levels of HBD-1, HBD-2, and HBD-3 mRNA expression were correlated with one another (P < 0.001). CONCLUSIONS: High levels of HBD-3 mRNA expression in healthy tissues suggest a potentially important protective role for defensins in the host immune response to infection by periodontal pathogens.

Case-Control Studies↗

PubMed2004

Human beta-defensins 2 and 3 demonstrate strain-selective activity against oral microorganisms.

Human beta-defensins 2 and 3 (HBD-2 and HBD-3) are inducible peptides present at sites of infection in the oral cavity. A few studies have reported broad-spectrum antimicrobial activity for both peptides. However, no comprehensive study has thoroughly investigated their potential against oral pathogens. The purpose of this study was to test the effectiveness of HBD-2 and HBD-3 against a collection of oral organisms (Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Peptostreptococcus micros, Actinomyces naeslundii, Actinomyces israelii, Streptococcus sanguis, Streptococcus mutans, Candida tropicalis, Candida parapsilosis, Candida krusei, Candida glabrata, and Candida albicans). Radial diffusion assays were used to test HBD-2 and HBD-3 activities against at least three strains of each species. There was significant variability in MICs, which was strain specific rather than species specific. MICs ranged from 3.9 to >250 micro g/ml for HBD-2 and from 1.4 to >250 micro g/ml for HBD-3. HBD-3 demonstrated greater antimicrobial activity and was effective against a broader array of organisms. Overall, aerobes were 100% susceptible to HBD-2 and HBD-3, whereas only 21.4 and 50% of the anaerobes were susceptible to HBD-2 and HBD-3, respectively. HBD-2 and HBD-3 also demonstrated strain-specific activity against the Candida species evaluated. Interestingly, an association between HBD-2 and HBD-3 activities was noted. This suggests that the two peptides may have similar mechanisms yet utilize distinct pathways. The lack of activity against specific anaerobic strains and Candida warrants further investigation of the potential resistance mechanisms of these organisms. Finally, the significant variability between strains underlies the importance of testing multiple strains when evaluating activities of antimicrobial peptides.

Anti-Infective Agents↗

PubMed2003

Bacterial penetration through canals of endodontically treated teeth in the presence or absence of the smear layer.

OBJECTIVES: The goal of this study is to determine if the smear layer affects the passage of bacteria through or around obturating material as evidenced by penetration of bacteria through and out the canal. Specifically, this study focused on determining the effect of the smear layer on the magnitude of bacterial penetration through the apical foramen. METHODS: Thirty extracted, maxillary central or lateral incisors were collected. Teeth were randomly assigned (10 teeth per group) to three groups: (1) smear layer removed, (2) smear layer present, and (3) negative control. Canal preparation and obturation using lateral condensation, gutta percha, and AH 26 sealer was performed on all of the teeth. Removal of the smear layer was accomplished by rinsing with 17% EDTA. The model systems consisted of an upper chamber attached to the cemento-enamel junction and a lower chamber at the apices of the teeth. Standardized bacterial suspensions containing Fusobacterium nucleatum, Campylobacter rectus, and Peptostreptococcus micros were inoculated into the upper chambers. Models were incubated anaerobically at 37 degrees C. At various times over a 60-day period, samples were taken from the lower chamber and spiral-plated on selective-differential media to determine numbers and types of bacteria. RESULTS: Leakage results were as follows: (1) smear layer present-6/10 leaked; (2) smear layer removed-0/10 leaked; (3) negative control-0/10 leaked. Profiles of bacterial leakage were similar among the groups. F. nucleatum was the predominant microorganism. CONCLUSIONS: This study indicated that removal of the smear layer reduced the leakage of bacteria through the root canal system.

Bismuth↗

PubMedDate not supplied

Human polymicrobial infections.

CONTEXT: Polymicrobial diseases, caused by combinations of viruses, bacteria, fungi, and parasites, are being recognised with increasing frequency. In these infections, the presence of one micro-organism generates a niche for other pathogenic micro-organisms to colonise, one micro-organism predisposes the host to colonisation by other micro-organisms, or two or more non-pathogenic micro-organisms together cause disease. STARTING POINT: Recently, Gili Regev-Yochay (JAMA 2004; 292: 716-20) and Debby Bogaert (Lancet 2004; 363: 1871-72), and their colleagues, suggested another interaction: microbial interference-the ability of Streptococcus pneumoniae carriage to protect against Staphylococcus aureus carriage, and the inverse effect of pneumococcal conjugate vaccination on the increased carriage of Staph aureus and Staph-aureus-related disease. Strep pneumoniae carriage protected against Staph aureus carriage, and the bacterial interference could be disrupted by vaccinating children with pneumococcal conjugate vaccines that reduced nasopharyngeal carriage of vaccine-type Strep pneumoniae. WHERE NEXT: The medical community is recognising the significance of polymicrobial diseases and the major types of microbial community interactions associated with human health and disease. Many traditional therapies are just starting to take into account the polymicrobial cause of diseases and the repercussions of treatment and prevention.

Antibiosis↗