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2.
Rural Remote Health ; 22(4): 7142, 2022 12.
Article in English | MEDLINE | ID: mdl-36455186

ABSTRACT

INTRODUCTION: Management of medication regimens and improvement of medication-taking behaviours may require various levels of support, education, engagement and barrier reduction from health services and or pharmacists. The use of dose administration aids (DAAs) may improve medication management for some people, and therefore may facilitate positive health benefits. This Australian study was informed by a literature review that found there was a dearth of data about Aboriginal and Torres Strait Islander peoples' use of DAAs. This study therefore aimed to understand the experiences of Aboriginal and Torres Strait Islander people living on the North Coast of New South Wales with DAAs and if the provision of DAAs supported medication-taking behaviours. METHODS: A mixed-methods approach that included data collected from a questionnaire and a series of focus groups was used in this study. Analysis was completed at three stages throughout the study. RESULTS: A total of 30 Aboriginal participants participated in the study. Participants lived in the area ranging from Tweed Heads to Port Macquarie. Twenty-six participants completed the questionnaire and 20 participated in the focus groups; 16 completed both. Participants felt they were managing their medications well. The study noted that, despite this assessment, 45% of focus group participants (9/20) missed taking medications regularly for various reasons. The medication regimens of participants were varied and potentially complex; for example, some participants were taking up to 23 individual doses of oral medications and insulin injections daily as a part of these regimens. Participants described their use of DAAs and how they supported their medication-taking both functionally and financially. Most participants reported that DAAs helped them manage their medications. The weekly or fortnightly provision of DAAs provided regular opportunities for pharmacists to interact with patients and/or their caregivers, supporting improved therapeutic relationships and possibly better health outcomes. CONCLUSION: DAAs were an important tool for improving medication management for most study participants. DAAs provided affordable and appropriate in-home support for patients to follow prescribed medication regimens. For the participants from this small study who used DAAs and viewed them as an important tool for managing medications, removal of financial subsidies that assist the provision of DAAs to Aboriginal and Torres Strait Islander peoples would have a negative effect on their ability to access them. This in turn may affect their medication-taking behaviours, potentially negatively affecting their long-term health outcomes. Further study regarding the Aboriginal and Torres Strait Islander patient experience of the use of DAAs over a longer period tracking medication adherence, and for a larger cohort of Aboriginal and Torres Strait Islander people, would be beneficial to understanding experience of use of DAAs on a wider scale.


Subject(s)
Indigenous Peoples , Racial Groups , Humans , New South Wales , Australia , Medication Adherence
3.
Rural Remote Health ; 20(3): 5706, 2020 07.
Article in English | MEDLINE | ID: mdl-32611194

ABSTRACT

INTRODUCTION: Rural and remote Australia has a shortage of allied health clinicians. The provision of quality rural placement experiences for allied health students has been a significant strategy to address these health workforce shortages. Service learning rural placements are providing allied health services in small rural towns where previously allied health services were limited or did not exist. Published literature has little detailed description of the origin or nature of particular placement programs. METHODS: An increase in Commonwealth funding for rural allied health clinical placements led to the development of an innovative service learning placement model in northern New South Wales, the Rural Community-Based Work-Ready Placement Program. During this placement, students were paired for 4-10 full-time weeks in a preschool, school or aged care facility. The program's fundamental properties included cultural and social equity education, providing continuous service throughout the year, and quality improvement initiatives in placement sites. The program was underpinned by an interdisciplinary approach that included interdisciplinary placements, interdisciplinary supervision and a structured interdisciplinary education program. RESULTS: The program required investment in stakeholder engagement and in the alignment of universities' requirements for student learning outcomes and the sites' specific needs. Clinical supervisors had to adapt to supervising students from various disciplines and universities across several sites, towns and services. The program provided students with opportunities to work autonomously, problem-solve and to initiate and implement quality improvement projects at each site. CONCLUSION: Careful selection of students, adequate preparation and management of students' expectations were important contributors to the success of the program. Providing a continuous service is an ongoing logistical challenge.


Subject(s)
Allied Health Personnel/education , Personnel Selection/organization & administration , Rural Health Services/organization & administration , Rural Population/statistics & numerical data , Allied Health Personnel/psychology , Capital Financing/organization & administration , Career Choice , Humans , New South Wales , Problem-Based Learning/organization & administration , Staff Development
4.
Cureus ; 11(5): e4695, 2019 May 17.
Article in English | MEDLINE | ID: mdl-31338270

ABSTRACT

Calciphylaxis is an uncommon disease that presents with painful ulceration and necrosis of the skin secondary to small vessel calcification and microvascular occlusion. Calciphylaxis carries a poor prognosis as the nonhealing wounds provide a port of entry for pathogens, predisposing these patients to infection and sepsis. Ulcers caused by calciphylaxis are most commonly seen in patients with end-stage renal disease (ESRD) but can also present in patients with normal electrolytes and kidney function. We report a case of a 42-year-old woman with a 10-year history of ESRD who developed rapidly progressing calciphylaxis in her legs and hand, starting three months after successful kidney transplantation. The relationship between kidney transplantation and calciphylaxis remains unclear. There are a handful of cases in which calciphylaxis has been treated by successful kidney transplant, however, other cases have been reported in which calciphylaxis developed after kidney transplantation.

5.
Dermatol Online J ; 25(12)2019 Dec 15.
Article in English | MEDLINE | ID: mdl-32045162

ABSTRACT

Lichen sclerosus (LS) is a chronic dermatologic condition characterized by atrophic porcelain-appearing plaques that can cause intense discomfort and eventually lead to destruction of local architecture. Lichen sclerosus most commonly arises in the anogenital area, but up to 20% of cases can present on extragenital skin. Rarely, LS can also present with hemorrhage and bullae; the mechanism by which this occurs is unknown. We report two cases of bullous hemorrhagic LS of the breast arising in 66-year-old and 77-year-old women. Bullous hemorrhagic LS of the breast is exceedingly rare, with few reported cases, and presents a diagnostic challenge to clinicians.


Subject(s)
Blister/etiology , Breast Diseases/pathology , Hemorrhage/etiology , Lichen Sclerosus et Atrophicus/pathology , Adult , Aged , Female , Humans , Lichen Sclerosus et Atrophicus/complications , Middle Aged
6.
Plast Reconstr Surg Glob Open ; 5(12): e1592, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29632771

ABSTRACT

Scalp defects greater than 2 cm in diameter are not usually amenable to primary closure and require local tissue rearrangement, grafting, tissue expansion, or prolonged second intention healing. Scalp flap reconstruction is a significant undertaking that requires elevation of a total flap surface area that is 3-6 times the size of the defect, often involves profuse bleeding, and can be challenging to perform without conscious sedation or general anesthesia. Anticoagulated and medically complex patients pose additional challenges and limit options for treatment. The pulley suture uses the mechanical advantage of the pulley to distribute tension across a wound and is useful in areas of high tension such as scalp wounds. For scalp wounds greater than 2 cm, pulley sutures are placed along the length of the wound. An assistant exerts equal tension on the pulley sutures, and the surgeon sequentially ties the sutures. The sutures are tightened and retied weekly until complete scalp closure is achieved. The pulley sutures can be used for rapid primary closure of scalp wounds up to 2.5-3.0 cm in diameter under local anesthesia. For scalp wounds larger than 3 cm, we have also found that pulley sutures can be progressively tightened yielding additional tissue expansion every week. Scalp wounds greater than 3.0 cm can be easily closed via primary repair and weekly tightening of pulley sutures without the need for flap reconstruction, traditional tissue expander placement, or second intention healing.

7.
Rural Remote Health ; 15: 3009, 2015.
Article in English | MEDLINE | ID: mdl-25711405

ABSTRACT

INTRODUCTION: In Australia, Home Medicines Review (HMR) has been found to be an important tool to raise awareness of medication safety, reduce adverse events and improve medication adherence. Aboriginal and Torres Strait Islander people are 'underserviced' by the HMR program and are the most likely of all Australians to miss out on HMRs despite their high burden of chronic disease and high rates of hospitalisation due to medication misadventure. The goal of this study was to explore Aboriginal and Torres Strait Islander perspectives of the Home Medicines Review program and their suggestions for an 'improved' or more readily accessible model of service. METHODS: Eighteen semi-structured focus groups were conducted with 102 Aboriginal and Torres Strait Islander patients at 11 Aboriginal Health Services (AHSs). Participants who were multiple medication users and understood English were recruited to the study by AHS staff. Seven focus groups were conducted for people who had already used the HMR program (User, n=23) and 11 focus groups were conducted for people who had not had an HMR (Non User, n=79). Focus groups were recorded, de-identified and transcribed. Transcripts were coded and analysed for themes. Focus groups continued and concepts were explored until no new findings were being generated and thus saturation of data occurred. RESULTS: Focus group participants who had not had an HMR had little or no awareness of the HMR program. All the participants felt that lack of awareness and promotion of the HMR program were contributing factors to the low uptake of the HMR program by Aboriginal and Torres Strait Islander people. Most participants felt that an HMR would assist them to better understand their medicines, would empower them to seek information about medicines, would improve relationships with health professionals and would increase the likelihood of medication adherence. Most of the User participants reported that the HMR interview had been very useful for learning more about their medicines. However, many reported that they found the process confusing and confronting. The majority of participants felt HMRs for Aboriginal and Torres Strait Islander patients should be organised by AHS staff, with patients being offered a choice of location for the HMR interview. Participants identified that Aboriginal Health Workers should play a key role in communication, knowledge translation, referral and follow-up. CONCLUSIONS: Current HMR rules impede rather than facilitate HMRs for Aboriginal and Torres Strait Islander people. Tailoring and remodelling of the HMR program is needed to increase the awareness, accessibility, acceptability and effectiveness of the HMR program for Aboriginal and Torres Strait Islander people.


Subject(s)
Health Services, Indigenous/organization & administration , Home Care Services/organization & administration , Medication Adherence/ethnology , Native Hawaiian or Other Pacific Islander , Patient Medication Knowledge/organization & administration , Adult , Australia , Community Pharmacy Services/organization & administration , Consumer Health Information/organization & administration , Cultural Competency , Female , Focus Groups , Humans , Male , Middle Aged , Patient Education as Topic/organization & administration , Patient Satisfaction , Polypharmacy , Professional-Patient Relations , Referral and Consultation/organization & administration
8.
Anesth Analg ; 117(3): 664-674, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23835455

ABSTRACT

The endothelial glycocalyx is a dynamic layer of macromolecules at the luminal surface of vascular endothelium that is involved in fluid homeostasis and regulation. Its role in vascular permeability and edema formation is emerging but is still not well understood. In this special article, we highlight key concepts of endothelial dysfunction with regards to the glycocalyx and provide new insights into the glycocalyx as a mediator of processes central to the development of pulmonary edema and lung injury.


Subject(s)
Acute Lung Injury/pathology , Endothelium/pathology , Glycocalyx/pathology , Pulmonary Edema/pathology , Algorithms , Capillary Permeability/physiology , Humans , Lung/surgery , Mechanotransduction, Cellular
9.
Curationis ; 36(1): E1-7, 2013.
Article in English | MEDLINE | ID: mdl-26697614

ABSTRACT

BACKGROUND: Nursing students, like other healthcare students, are at high risk of occupational exposure to blood and bodily fluids. Studies have shown that use of the Universal Precautions (UPs) lowers this risk, but do students know and practise these precautions? OBJECTIVES: This study investigated the knowledge and practice of undergraduate nursing students regarding the UPs, and whether there was a correlation between knowledge of the UPs and their practice. METHOD: This was a descriptive quantitative study amongst undergraduate nursing students in years 2­4 (n=253), who were selected by means of stratified random sampling. A questionnaire was administered to the participants by the researcher. The data collected were analysed through use of the Statistical Package for Social Sciences (SPSS 16.0) and content analysis. RESULTS: It was established that there was indeed a lack of knowledge regarding the UPs, and that the students' self-reported practice of the UPs was poor. There was no statistically significant correlation between knowledge and practice of the UPs. CONCLUSION: More structured educational programmes are needed to improve both knowledge and practice of the UPs. These programmes should be offered across all nursing student study years as continuous professional development.


Subject(s)
Students, Nursing , Universal Precautions , Health Knowledge, Attitudes, Practice , Humans , Knowledge , Surveys and Questionnaires
10.
PLoS One ; 7(11): e49076, 2012.
Article in English | MEDLINE | ID: mdl-23185294

ABSTRACT

Vitamin D deficiency is increasing in incidence around the world. Vitamin D, a fat-soluble vitamin, has documented effects on the innate and adaptive immune system, including macrophage and T regulatory (Treg) cell function. Since Treg cells are important in acute lung injury resolution, we hypothesized that vitamin D deficiency increases the severity of injury and delays injury resolution in lipopolysaccharide (LPS) induced acute lung injury. Vitamin D deficient mice were generated, using C57BL/6 mice, through diet modification and limited exposure to ultraviolet light. At 8 weeks of age, vitamin D deficient and sufficient mice received 2.5 g/kg of LPS or saline intratracheal. At 1 day, 3 days and 10 days, mice were anesthetized and lung elastance measured. Mice were euthanized and bronchoalveolar lavage fluid, lungs and serum were collected. Ex vivo neutrophil chemotaxis was evaluated, using neutrophils from vitamin D sufficient and deficient mice exposed to the chemoattractants, KC/CXCL1 and C5a, and to bronchoalveolar lavage fluid from LPS-exposed mice. We found no difference in the degree of lung injury. Leukocytes were mildly decreased in the bronchoalveolar fluid of vitamin D deficient mice at 1 day. Ex-vivo, neutrophils from vitamin D deficient mice showed impaired chemotaxis to KC but not to C5a. Vitamin D deficiency modestly impairs neutrophil chemotaxis; however, it does not affect lung injury or its resolution in an LPS model of acute lung injury.


Subject(s)
Lung Injury/blood , Lung Injury/pathology , Vitamin D/blood , Animals , Body Composition , Chemotaxis , Feeding Behavior , Inflammation/blood , Inflammation/pathology , Lipopolysaccharides , Lung/pathology , Mice , Mice, Inbred C57BL , Neutrophils/pathology
11.
Physiol Genomics ; 37(3): 239-48, 2009 May 13.
Article in English | MEDLINE | ID: mdl-19276240

ABSTRACT

Mechanical ventilation is a life-saving intervention in patients with respiratory failure. However, human and animal studies have demonstrated that mechanical ventilation using large tidal volumes (>or=12 ml/kg) induces a potent inflammatory response and can cause acute lung injury. We hypothesized that mechanical ventilation with a "noninjurious" tidal volume of 10 ml/kg would still activate a transcriptional program that places the lung at risk for severe injury. To identify key regulators of this transcriptional response, we integrated gene expression data obtained from whole lungs of spontaneously breathing mice and mechanically ventilated mice with computational network analysis. Topological analysis of the gene product interaction network identified Jun and Fos families of proteins as potential regulatory hubs. Electrophoretic mobility gel shift assay confirmed protein binding to activator protein-1 (AP-1) consensus sequences, and supershift experiments identified JunD and FosB as components of ventilation-induced AP-1 binding. Specific recruitment of JunD to the regulatory region of the F3 gene by mechanical ventilation was confirmed by chromatin immunoprecipitation assay. In conclusion, we demonstrate a novel computational framework to systematically dissect transcriptional programs activated by mechanical ventilation in the lung, and show that noninjurious mechanical ventilation initiates a response that can prime the lung for injury from a subsequent insult.


Subject(s)
Gene Expression Profiling , Lung/metabolism , Respiration, Artificial/methods , Ventilator-Induced Lung Injury/genetics , Animals , Cell Line , Chromatin Immunoprecipitation , Cluster Analysis , Computer Simulation , Electrophoretic Mobility Shift Assay , Gene Regulatory Networks , Inflammation Mediators/metabolism , Lung/pathology , Lung/physiopathology , Male , Mice , Mice, Inbred C57BL , Models, Genetic , Oligonucleotide Array Sequence Analysis , Protein Binding , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-fos/metabolism , Proto-Oncogene Proteins c-jun , Reverse Transcriptase Polymerase Chain Reaction , Tidal Volume/physiology , Transcription Factor AP-1/genetics , Transcription Factor AP-1/metabolism , Ventilator-Induced Lung Injury/metabolism , Ventilator-Induced Lung Injury/physiopathology
12.
Endocr Pract ; 13(5): 542-9, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17872357

ABSTRACT

OBJECTIVE: To review the controversy related to the widespread use of intensive insulin treatment (IIT) to maintain normoglycemia and of glucocorticoid replacement therapy in patients with sepsis in the intensive care unit (ICU). METHODS: We performed a MEDLINE search of the literature using a combination of words (critical/intensive care, endocrinology/endocrine, glucocorticoid/adrenal, insulin) to identify original studies and reviews on glucocorticoid therapy and IIT in the ICU. RESULTS: Glucocorticoid replacement therapy is advocated for patients with sepsis who have relative adrenal insufficiency. The current definition of relative adrenal insufficiency is poorly supported, and validated endocrine criteria that consistently identify ICU patients likely to benefit from glucocorticoid therapy are not yet available. IIT benefits postoperative patients at high risk of infection and patients who remain in the ICU more than 3 days. Potential harm caused by early IIT administration in medical ICU patients remains controversial. The role of early nutritional supplementation in major studies about IIT is largely unexplored. Improvements in insulin infusion protocols are needed to reduce the risk of hypoglycemia related to IIT. CONCLUSION: Endocrine therapy in the ICU is entering a new era. Controversies remain related to glucocorticoid and insulin therapy even as interest in new, and old, endocrine therapies is being revived.


Subject(s)
Critical Care/methods , Critical Illness/therapy , Glucocorticoids/therapeutic use , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Humans , Intensive Care Units
14.
Spine (Phila Pa 1976) ; 27(18): 2067-71, 2002 Sep 15.
Article in English | MEDLINE | ID: mdl-12634571

ABSTRACT

STUDY DESIGN: A prospective, randomized trial comparing Epoetin alfa (Procrit) with placebo saline injection to determine effectiveness in increasing erythropoietic recovery in complex spine deformity surgery. OBJECTIVES: To determine if Epoetin alfa can allow preoperative autologous donation completion more effectively and reduce perioperative homologous blood transfusion. SUMMARY OF BACKGROUND DATA: The use of Epoetin alfa has been studied, primarily in the arthroplasty literature, for its effectiveness in decreasing transfusion requirements and increasing hemoglobin levels. It has not been studied in patients undergoing complex spine deformity surgery. METHODS: A total of 48 patients were prospectively randomized into an Epoetin alfa group and a control group. All patients attempted to donate 4 units of preoperative autologous donation at weekly intervals; 40,000 units of Epoetin alfa were injected subcutaneously at the time of preoperative autologous donation in the Epoetin alfa group. Hematocrit levels were recorded weekly during the donation process and daily in the preoperative period. RESULTS: Preoperative autologous donation was completed more effectively in the patients receiving Epoetin alfa. Epoetin alfa resulted in statistically higher hematocrit levels during preoperative autologous donation and perioperatively (P < 0.005). Homologous transfusion was decreased by 2.4 units and hospital stay was 1.8 days shorter in patients receiving Epoetin alfa. CONCLUSION: Patients who received Epoetin alfa were able to complete preoperative autologous donation more effectively, increase erythropoietic recovery, decrease homologous transfusion requirements, and had shorter hospital stays.


Subject(s)
Blood Transfusion, Autologous , Erythropoietin/administration & dosage , Preoperative Care/methods , Spinal Curvatures/surgery , Spinal Fusion , Adult , Aged , Blood Donors/statistics & numerical data , Blood Loss, Surgical/statistics & numerical data , Constipation/etiology , Contraindications , Epoetin Alfa , Erythropoietin/adverse effects , Female , Fever/etiology , Hematocrit/statistics & numerical data , Humans , Injections, Subcutaneous , Length of Stay/statistics & numerical data , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Nausea and Vomiting/etiology , Prospective Studies , Recombinant Proteins , Sepsis/etiology , Spinal Fusion/adverse effects , Spinal Fusion/methods , Treatment Outcome
15.
Women Health ; 26(3): 15-26, 1997.
Article in English | MEDLINE | ID: mdl-9501399

ABSTRACT

The purpose of this study was to investigate the effect of physicians' gender when sex-specific conditions are being treated in a country where almost half of the physicians are women. Five Finnish surveys originally conducted for other purposes were reanalyzed. Two surveys examined physicians' and medical students' views about hormone therapy during and after menopause, one survey examined medical students' attitudes about medicines, one survey examined physicians' obstetric practices, and one examined contraceptive counselling. All the surveys showed more similarities than differences in the clinical decision-making of women and men physicians. In opinions about menopause the physician's medical specialty was more important than gender. Physicians' obstetrical practices were also similar in five cases out of six, but in one situation where medical factors were not a deciding issue, women physicians acted differently. These results suggest that socialization into the medical profession makes physicians' practices more alike and diminishes gender differences.


PIP: To determine the effect of gender on the type of reproductive health treatment offered to women in a setting where half of the physicians are female, this study reanalyzed data collected from five surveys in Finland. The surveys were originally conducted to investigate the views of physicians (74% of 500 responding) and medical students (74% of 125 responding) about menopausal hormone replacement therapy, the attitudes of medical students about prescribing hormones, obstetric practices (83% of 90 responding), and contraceptive counseling (74% of 480 responding). It was found that the number of menopausal patients was highest for female gynecologists, followed by male gynecologists, female physicians, and male physicians. Female and male gynecologists offered similar recommendations for hormone replacement therapy, but female physicians were more likely to prescribe hormones for prevention only. Results for medical students were not influenced by gender. The only significant difference in obstetric practice was that female obstetricians were three times more likely than males to induce labor for convenience. While equal numbers of female and male physicians prescribed oral contraceptives and IUDs, females were more likely to prescribe condoms, implants, and diaphragms. It is concluded that professional identification among these physicians was stronger than gender influences.


Subject(s)
Attitude of Health Personnel , Contraception/psychology , Estrogen Replacement Therapy/psychology , Physicians/psychology , Students, Medical/psychology , Counseling , Female , Finland , Humans , Male , Medicine , Postmenopause/psychology , Sex Factors , Specialization , Surveys and Questionnaires
16.
Matrix ; 11(4): 296-301, 1991 Aug.
Article in English | MEDLINE | ID: mdl-1656176

ABSTRACT

Degradation of cartilage in rheumatoid arthritis (RA) may be in part due to release of collagenase from specific granules of polymorphonuclear neutrophil leukocytes (PMNs) during degranulation. We decided to study, not synovial fluid (SF) collagenase, but PMN collagenase reserves. PMN were isolated from parallel SF and peripheral blood (PB) samples obtained from 7-arthritis patients. PMNs were stimulated in vitro by tetradecanoyl-phorbol-13-acetate (TPA). Collagenase activity in the supernatant without and with phenylmercuric chloride activation was studied. Compared to PB PMNs, there was no consistent decrease in the total collagenase reserves in the inflammatory SF PMNs. This suggests that the release of collagenase in the inflammatory synovial fluid does not deplete SF PMNs of the collagenase synthesized at the myelocyte stage. The role of PMN collagenase in pathogenesis of cartilage destruction would then seem to be more dependent on local release and autoactivation at cartilage surface by adherent PMNs and not excessive collagenase release from free floating SF PMNs at single cell level. Furthermore, under the experimental conditions used the proportion of collagenase released in active form was higher in SF PMN specimens than in PB PMN specimens (p less than 0.01). The predominant collagenous component of adult cartilage, native type II collagen, was degraded by PMN collagenase as fast as native type I collagen. These findings suggest an important role for this enzyme in destruction of the free cartilage surface in RA.


Subject(s)
Arthritis, Rheumatoid/enzymology , Blood Cells/chemistry , Microbial Collagenase/analysis , Neutrophils/chemistry , Synovial Fluid/cytology , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/metabolism , Collagen/metabolism , Humans , Tetradecanoylphorbol Acetate/pharmacology , Time Factors
17.
Scand J Dent Res ; 97(4): 346-54, 1989 Aug.
Article in English | MEDLINE | ID: mdl-2552568

ABSTRACT

The existing forms of neutral proteases present in inflamed human gingiva were examined. Neutral 2 M K Cl extracts of inflamed human gingival tissue were fractionated by gel filtration on Sephacryl S-200 and the fractions were assayed for collagenase, trypsin-, chymotrypsin-, and elastase-like proteases. Apparent molecular weights of 80-85 kDa were obtained for trypsin-, chymotrypsin-, and elastase-like proteases, and 70-75 kDa for latent collagenase. Further fractionation of high molecular weight proteases on Con A-Sepharose revealed that, unlike collagenase, chymotrypsin- and elastase-like proteases, the trypsin-like protease was bound by the affinity column. Native human placental type IV (basement membrane) collagen was degraded by chymotrypsin-like and elastase-like proteases but not by the trypsin-like protease. This degradation was inhibited by phenylmethyl sulfonyl fluoride and EDTA. The serine proteases also degraded efficiently denatured type I collagen. No correlation of the activities of trypsin-like protease and the other proteolytic enzymes was found in extracts of 18 individual gingival specimens. Significant correlation, however, was noted between collagenase and gelatinase. The gingival culture studies showed that, while the highest activity of the trypsin-, chymotrypsin-, and elastase-like enzymes were measured in medium during first days of the culture, collagenase and gelatinase activities increased up to the fourth day of culture and stayed high until the end of the culture. These results suggest that the neutral proteases that may participate in the periodontal tissue destruction are produced by different cell types of gingiva.


Subject(s)
Chymotrypsin/isolation & purification , Gingiva/enzymology , Microbial Collagenase/isolation & purification , Pancreatic Elastase/isolation & purification , Periodontitis/enzymology , Trypsin/isolation & purification , Chromatography, Affinity , Chromatography, Gel , Chronic Disease , Chymotrypsin/antagonists & inhibitors , Chymotrypsin/pharmacology , Collagen/metabolism , Culture Techniques , Humans , Microbial Collagenase/antagonists & inhibitors , Molecular Weight , Pancreatic Elastase/antagonists & inhibitors , Pancreatic Elastase/pharmacology , Trypsin Inhibitors/pharmacology
19.
Proc Finn Dent Soc ; 85(1): 3-11, 1989.
Article in English | MEDLINE | ID: mdl-2543968

ABSTRACT

The role of human neutrophil proteases in the further degradation of the native triple-helical characteristic cleavage products 3/4- and 1/4-collagen fragments generated by neutrophil interstitial collagenase from native type I collagen was studied. Purified human neutrophil collagenase did not further degrade the characteristic collagen fragments whether they were in triple-helical (native collagen) or random-coil (gelatin) conformation. Neutrophil extract treated with 1 mM phenylmercuric chloride (PMC) degraded native type I collagen at +37 degrees C producing multiple protein bands. Neutrophil extract at +18 degrees C in the presence of the serine protease inhibitors phenylmethylsulfonyl fluoride and banzamidine did not degrade native type I collagen. Inclusion of PMC to active latent collagenase caused neutrophil extract to degrade native type I collagen to 3/4- and 1/4-fragments. In addition, native 3/4- and 1/4-fragments were further degraded in a time-dependent manner by PMC-treated neutrophil extract. Both native 3/4- and 1/4-collagen fragments were degraded by specific rather than by multiple cleavage. Further fragmentation was inhibited by divalent cation chelators EDTA and 1,10-phenanthroline. The results indicate the presence of latent metalloprotease(s), as distinct from collagenase, gelatinase and serine proteases, that are capable of further degrading by specific cleavage both native 3/4- and 1/4-collagen fragments generated by collagenase in human neutrophils. The enzyme(s) may augment the action of collagenase and other neutral proteases in connective tissue destruction associated with the etiopathogenesis of periodontal diseases.


Subject(s)
Collagen/metabolism , Microbial Collagenase/metabolism , Neutrophils/analysis , Peptide Hydrolases/isolation & purification , Electrophoresis, Polyacrylamide Gel , Humans , Peptide Hydrolases/metabolism , Protease Inhibitors
20.
Int J Tissue React ; 11(4): 153-9, 1989.
Article in English | MEDLINE | ID: mdl-2561361

ABSTRACT

Collagenases are known to be associated with tissue destruction in chronic inflammatory diseases such as periodontal diseases and rheumatoid arthritis. Collagenases are secreted by circulating inflammatory cells (polymorphonuclear leukocytes and monocytes), resident mesenchymal cells and epithelial cells in latent forms, which can be activated by proteases and compounds reacting with protein thiol groups. We have studied here the effects of oxygen-derived free radicals (ODFR) on latent human neutrophil collagenase. Also, in order to elucidate the cellular sources of collagenases, the ability of human gingival crevicular fluid (GCF) collagenases both from adult periodontitis (AP) and localized juvenile periodontitis (LJP) patients to degrade soluble interstitial collagen types I and II was studied. ODFR generated by the xanthine oxidase/hypoxanthine system in the presence of trace amounts of iron and EDTA activated latent neutrophil collagenase to an equal extent as the known activators phenylmercuric chloride and gold thioglucose. ODFR activation was inhibited by desferoxamine and mannitol as well as by superoxide dismutase and catalase. Clear differences in the susceptibility of collagen types I and II to AP and LJP GCF collagenases were observed. AP GCF collagenase degraded type I and II collagens at equal rates, resembling the substrate-specificity of human neutrophil collagenase. LJP GCF collagenase degraded type I collagen considerably faster than type II collagen, which was only negligibly degraded. This corresponds to the substrate specificity of fibroblast collagenase. Zymographic evaluation of gelatinolytic proteases showed the presence of 90 and 68 kD gelatinases in both AP and LJP GCF. Non-proteolytic means apparently provide a potent activation pathway of neutrophil collagenase in vivo and the hydroxyl radical was identified to be one of the potent activating oxidants.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Extracellular Matrix/metabolism , Microbial Collagenase/blood , Neutrophils/enzymology , Oxygen/pharmacology , Periodontal Diseases/enzymology , Body Fluids/enzymology , Collagen/metabolism , Electrophoresis, Polyacrylamide Gel , Enzyme Activation , Free Radicals , Gingiva/enzymology , Humans , Microbial Collagenase/isolation & purification , Microbial Collagenase/physiology , Molecular Weight , Periodontal Diseases/metabolism
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