Biomedical subjects

Pauli A Puolakkainen

Publications and source records attributed to Pauli A Puolakkainen.

7 recordsLinked to original sources

PubMed2005

Matricellular homologs in the foreign body response: hevin suppresses inflammation, but hevin and SPARC together diminish angiogenesis.

Implanted foreign materials, used to restore or assist tissue function, elicit an initial acute inflammatory response followed by chronic fibrosis that leads to the entrapment of the biomaterial in a thick, poorly vascularized collagenous capsule. Matricellular proteins, secreted macromolecules that interact with extracellular matrix proteins but do not in themselves serve structural roles, have been identified as important mediators of the foreign body response that includes inflammation, angiogenesis, and collagen synthesis and assembly. In this report we delineate functions of hevin and SPARC, two homologs of the SPARC family of matricellular proteins, in the foreign body response. Despite their sequence similarity, hevin and SPARC mediate different aspects of this fibrotic response. Using mice with targeted gene deletions, we show that hevin is central to the progression of biomaterial-induced inflammation whereas SPARC regulates the formation of the collagenous capsule. Although vascular density within the capsule is unaltered in the absence of either protein, SPARC-hevin double-null capsules show substantially increased numbers of vessels, indicating compensatory functions for these two proteins in the inhibition of angiogenesis. These results provide important information for further development of implant technology.

Animals↗

PubMed2005

Bifidobacterium Lactis sp. 420 up-regulates cyclooxygenase (Cox)-1 and down-regulates Cox-2 gene expression in a Caco-2 cell culture model.

Cyclooxygenases (Cox) -1 and -2 play important roles in gastrointestinal health; chronic overexpression of Cox-2 is associated with inflammatory and cancerous disease, whereas Cox-1 is expressed constitutively. We studied the effects of two probiotic (Bifidobacterium lactis sp. 420 and Lactobacillus acidophilus) and two control microorganisms (Escherichia coli and Salmonella enteritidis) and four microbial metabolites (acetate, butyrate, lactate and propionate) on the expression levels of the Cox isoforms in the enterocyte-like cell line Caco-2. Butyrate, which is anticarcinogenic, resulted in an 85% down-regulation of Cox-2 and a 37-fold increase in Cox-1 transcription. Propionate gave similar results (72% reduction of Cox-2, 23-fold induction of Cox-1), but lactate and acetate had no effect on Cox expression profile. Bifidobacterium sp. 420, which produces acetate and lactate but no butyrate or propionate, shared the Cox-1-increasing and Cox-2-silencing properties of butyrate and propionate, whereas L. acidophilus was similar to E. coli and S. enteritidis in having no effect on the Cox-1/Cox-2 ratio. For the first time, we therefore demonstrate evidence for a direct relationship between a probiotic bacterial strain and host Cox expression profile, suggesting that modulation of Cox expression may be an important factor in the potential anti-inflammatory and anticarcinogenic properties of some probiotics.

Acetates↗

PubMed2005

SPARC-thrombospondin-2-double-null mice exhibit enhanced cutaneous wound healing and increased fibrovascular invasion of subcutaneous polyvinyl alcohol sponges.

Secreted protein acidic and rich in cysteine (SPARC) and thrombospondin-2 (TSP-2) are structurally unrelated matricellular proteins that have important roles in cell-extracellular matrix (ECM) interactions and tissue repair. SPARC-null mice exhibit accelerated wound closure, and TSP-2-null mice show an overall enhancement in wound healing. To assess potential compensation of one protein for the other, we examined cutaneous wound healing and fibrovascular invasion of subcutaneous sponges in SPARC-TSP-2 (ST) double-null and wild-type (WT) mice. Epidermal closure of cutaneous wounds was found to occur significantly faster in ST-double-null mice, compared with WT animals: histological analysis of dermal wound repair revealed significantly more mature phases of healing at 1, 4, 7, 10, and 14 days after wounding, and electron microscopy showed disrupted ECM at 14 days in these mice. ST-double-null dermal fibroblasts displayed accelerated migration, relative to WT fibroblasts, in a wounding assay in vitro, as well as enhanced contraction of native collagen gels. Zymography indicated that fibroblasts from ST-double-null mice also produced higher levels of matrix metalloproteinase (MMP)-2. These data are consistent with the increased fibrovascular invasion of subcutaneous sponge implants seen in the double-null mice. The generally accelerated wound healing of ST-double-null mice reflects that described for the single-null animals. Importantly, the absence of both proteins results in elevated MMP-2 levels. SPARC and TSP-2 therefore perform similar functions in the regulation of cutaneous wound healing, but fine-tuning with respect to ECM production and remodeling could account for the enhanced response seen in ST-double-null mice.

Animals↗

PubMed2004

Enhanced growth of pancreatic tumors in SPARC-null mice is associated with decreased deposition of extracellular matrix and reduced tumor cell apoptosis.

SPARC, a matricellular glycoprotein, modulates cellular interaction with the extracellular matrix (ECM). Tumor growth and metastasis occur in the context of the ECM, the levels and deposition of which are controlled in part by SPARC. Tumor-derived SPARC is reported to stimulate or retard tumor progression depending on the tumor type, whereas the function of host-derived SPARC in tumorigenesis has not been explored fully. To evaluate the function of endogenous SPARC, we have examined the growth of pancreatic tumors in SPARC-null (SP(-/-)) mice and their wild-type (SP(+/+)) counterparts. Mouse pancreatic adenocarcinoma cells injected s.c. grew significantly faster in SP(-/-) mice than cells injected into SP(+/+) animals, with mean tumor weights at sacrifice of 0.415 +/- 0.08 and 0.086 +/- 0.03 g (P < 0.01), respectively. Lack of endogenous SPARC resulted in decreased collagen deposition and fiber formation, alterations in the distribution of tumor-infiltrating macrophages, and decreased tumor cell apoptosis. There was no difference in microvessel density of tumors from SP(-/-) or SP(+/+) mice. However, tumors grown in SP(-/-) had a lower percentage of blood vessels that expressed smooth muscle alpha-actin, a marker of pericytes. These data reflect the importance of ECM deposition in regulating tumor growth and demonstrate that host-derived SPARC is a critical factor in the response of host tissue to tumorigenesis.

Animals↗

PubMed2003

Long-term health-related quality of life in survivors of severe acute pancreatitis.

OBJECTIVE: To evaluate the health-related quality of life (HRQL) and postdischarge outcome after severe acute pancreatitis. DESIGN AND SETTING: Observational study in a department of surgery (surgical and general intensive care unit) in a tertiary care hospital. PATIENTS AND PARTICIPANTS: Of 283 patients with severe acute pancreatitis 211 survived; during a follow-up period an additional 27 died. The Rand 36-item Health Survey with accessory question was mailed to 174 eligible patients. The final study population comprised 145 patients (83% response rate). Age- and sex-matched Finnish population scores were compared with the study population; accessory questions were analyzed separately. RESULTS: No clinically significant differences were found in long-term HRQL between study patients and the general population. Of the 145 patients 87% returned to work, 27% suffered recurrent pancreatitis, and 43% developed diabetes. Of 113 patients with alcohol-induced severe acute pancreatitis 30% were abstinent and 28% problem drinkers, alcohol-dependent, or alcoholics. CONCLUSIONS: Up to 13% of severe acute pancreatitis patients surviving initial hospitalization die within a few years. Among the survivors long-term HRQL is comparable to that of the normal population. The majority return to work and reduce their alcohol consumption markedly.

Acute Disease↗

PubMed2003

Predicting fatal outcome in the early phase of severe acute pancreatitis by using novel prognostic models.

BACKGROUND/AIMS: Survival in acute pancreatitis and particularly in severe acute and necrotizing pancreatitis is a combination of therapy-associated and patient-related factors. There are only few relevant methods for predicting fatal outcome in acute pancreatitis. Scores such as Ranson, Imrie, Blamey, and APACHE II are practical in assessing the severity of the disease, but are not sufficiently validated for predicting fatal outcome among patients with severe acute pancreatitis. The aim of this study was to construct a novel prediction model for predicting fatal outcome in the early phase of severe acute pancreatitis (SAP) and to compare this model with previously reported predictive systems. METHODS: Hospital records of 253 patients with SAP were retrospectively analyzed. 234 patients with adequate data were included to the test set to construct five logistic regression and three artificial neural network (ANN) models. Two models were tested in an independent prospective validation set of 60 consecutive patients with SAP and compared with previously reported predictive systems. RESULTS: The prediction model considered optimal was a logistic model with four variables: age, highest serum creatinine value within 60-72 h from primary admission, need for mechanical ventilation, and chronic health status. In the validation set, the predictive accuracy, determined by the area under the receiver operating characteristic curve value, was 0.862 for the chosen model, 0.847 for the ANN model using eight variables, 0.817 for APACHE II, 0.781 for multiple organ dysfunction score, 0.655 for Ranson, and 0.536 for Imrie scores. CONCLUSIONS: Ranson and Imrie scores are inaccurate indicators of the mortality in SAP. A novel predictive model based on four variables can reach at least the same predictive performance as the APACHE II system with 14 variables.

APACHE↗

PubMed2002

Multiple organ dysfunction associated with severe acute pancreatitis.

OBJECTIVE: To compare three different multiple organ dysfunction scores in predicting hospital mortality rates and to discover which one best assesses organ dysfunction/failure in patients with severe acute pancreatitis in a general intensive care unit. DESIGN: Retrospective, observational study. SETTING: Surgical department and a ten-bed general intensive care unit in a tertiary care hospital. PATIENTS: Among the 178 consecutive patients admitted to the surgical department with severe acute pancreatitis from 1994 to 1998, 113 patients treated in the general intensive care unit underwent study. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Clinical and laboratory data were collected during a period of 35 days. Acute Physiology and Chronic Health Evaluation (APACHE) II, Multiple Organ Dysfunction (MOD) score, Sequential Organ Failure Assessment (SOFA) score, and Logistic Organ Dysfunction (LOD) score were calculated and compared regarding hospital mortality rate. In addition, daily maximum score and a total maximum score (sum of the highest values for each organ dysfunction) were calculated for all three scores. The area under the receiver operating characteristic curve was used as a measure of accuracy of the scores. The highest accuracy was revealed with daily maximum scores with the area under the receiver operating characteristic curve 0.847 for SOFA, 0.844 for MOD, and 0.836 for LOD. According to the maximum SOFA score, the highest mortality rate was associated with liver (83%, p <.001) and renal (63%, p <.001) failures. The mortality ratio with two organ failures ranged from 50% to 91%. The highest mortality rate (91%) was for a combination of hepatic and renal failure. In multiple logistic regression analysis, only hepatic, renal, and cardiovascular failure and previous cardiovascular medication were independent risk factors for hospital mortality. CONCLUSION: In patients with severe acute pancreatitis, organ dysfunction scores (MOD, SOFA, LOD) show good accuracy, comparable with APACHE II in predicting hospital mortality. The maximum daily organ dysfunction scores were simple and useful in assessing multiple organ dysfunction and in predicting hospital mortality rates of patients with severe acute pancreatitis.

APACHE↗