Publications by authors named "Karin Pichler"

23 Publications

  • Page 1 of 1

Maternal Vaginal spp. Colonization in Early Pregnancy Is Associated with Adverse Short- and Long-Term Outcome of Very Preterm Infants.

Children (Basel) 2021 Apr 3;8(4). Epub 2021 Apr 3.

Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria.

Vaginal colonization with () spp. has been shown to be associated with adverse pregnancy outcome; however, data on neonatal outcome are scarce. The aim of the study was to investigate whether maternal vaginal colonization with spp. in early pregnancy represents a risk factor for adverse short- or long-term outcome of preterm infants. Previously, 4330 pregnant women were enrolled in an observational multicenter study, analyzing the association between vaginal spp. colonization and spontaneous preterm birth. spp. colonization was diagnosed via PCR analysis from vaginal swabs. For this study, data on short-term outcome were collected from medical records and long-term outcome was examined via Bayley Scales of Infant Development at 24 months adjusted age. Two-hundred-and-thirty-eight children were born <33 weeks gestational age. After exclusion due to asphyxia, malformations, and lost-to-follow-up, data on short-term and long-term outcome were available from 222 and 92 infants, respectively. Results show a significant association between vaginal spp. colonization and severe intraventricular hemorrhage (10.4% vs. 2.6%, = 0.03), retinopathy of prematurity (21.7% vs. 10.3%, = 0.03), and adverse psychomotor outcome (24.3% vs. 1.8%, OR 13.154, 95%CI 1.6,110.2, = 0.005). The data suggest an association between vaginal spp. colonization in early pregnancy and adverse short- and long-term outcome of very preterm infants.
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http://dx.doi.org/10.3390/children8040276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066242PMC
April 2021

Impact of Different Types of Nosocomial Infection on the Neurodevelopmental Outcome of Very Low Birth Weight Infants.

Children (Basel) 2021 Mar 9;8(3). Epub 2021 Mar 9.

Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Waehringer Gürtel 18-20, 1090 Vienna, Austria.

Nosocomial infections (NIs) are important conditions associated with mortality and morbidity in very low birth weight infants (VLBWIs). The aim of this study was to investigate the impact of NIs and the different subtypes on neurodevelopmental outcomes in a cohort of VLBWIs. VLBWIs born with a gestational age between 23 and 31 weeks in a level III neonatal center were enrolled. Neonatal morbidities as well as the neurodevelopmental outcome at 2 years of corrected age were analyzed. Six-hundred infants completed the study successfully. Of these, 38% experienced an NI episode. NIs were associated with an increased risk of neonatal complications, such as brain injury, bronchopulmonary dysplasia (BPD) and death, and were a significant risk factor for adverse motor development at 2 years of corrected age in our cohort of VLBWIs. The negative impact of NIs on neurodevelopmental outcomes was particularly associated with necrotizing enterocolitis (NEC), suspected NIs and Gram-positive NIs. This study demonstrated that NIs are a significant risk factor for both morbidity and mortality as well as adverse neurodevelopmental outcomes in VLBWIs.
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http://dx.doi.org/10.3390/children8030207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000764PMC
March 2021

Impact of the Fontan Operation on Organ Systems.

Cardiovasc Hematol Disord Drug Targets 2019 ;19(3):205-214

Department for Pediatric Cardiology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.

In patients having undergone the Fontan operation, besides the well discussed changes in the cardiac, pulmonary and gastrointestinal system, alterations of further organ systems including the hematologic, immunologic, endocrinological and metabolic are reported. As a medical adjunct to Fontan surgery, the systematic study of the central role of the liver as a metabolizing and synthesizing organ should allow for a better understanding of the pathomechanism underlying the typical problems in Fontan patients, and in this context, the profiling of endocrinological and metabolic patterns might offer a tool for the optimization of Fontan follow-up, targeted monitoring and specific adjunct treatment.
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http://dx.doi.org/10.2174/1871529X19666190211165124DOI Listing
August 2020

Viral Respiratory Infections in the Neonatal Intensive Care Unit-A Review.

Front Microbiol 2018 19;9:2484. Epub 2018 Oct 19.

Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.

Although infrequent, respiratory viral infections (RVIs) during birth hospitalization have a significant impact on short- and long-term morbidity in term and preterm neonates. RVI have been associated with increased length of hospital stay, severe disease course, unnecessary antimicrobial exposure and nosocomial outbreaks in the neonatal intensive care unit (NICU). Virus transmission has been described to occur via health care professionals, parents and other visitors. Most at risk are infants born prematurely, due to their immature immune system and the fact that they stay in the NICU for a considerable length of time. A prevalence of RVIs in the NICU in symptomatic infants of 6-30% has been described, although RVIs are most probably underdiagnosed, since testing for viral pathogens is not performed routinely in symptomatic patients in many NICUs. Additional challenges are the wide range of clinical presentation of RVIs, their similarity to bacterial infections and the unreliable detection methods prior to the era of molecular biology based technologies. In this review, current knowledge of early-life RVI in the NICU is discussed. Reviewed viral pathogens include human rhinovirus, respiratory syncytial virus and influenza virus, and discussed literature is restricted to reports based on modern molecular biology techniques. The review highlights therapeutic approaches and possible preventive strategies. Furthermore, short- and long-term consequences of RVIs in infants hospitalized in the NICU are discussed.
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http://dx.doi.org/10.3389/fmicb.2018.02484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202802PMC
October 2018

Impact and Time Course of Clostridium difficile Colonization in Very Low Birth Weight Infants.

Neonatology 2018 12;114(2):149-154. Epub 2018 Jun 12.

Division of Neonatology, Intensive Care, and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.

Background: Clostridium difficile is a gram-positive, anaerobic spore-forming, toxin-producing bacillus, which is one of the most common causes for health care-associated infections. High colonization rates in clinically asymptomatic neonates and infants have been described, although most studies go back to the early 1980 and 1990s, and were carried out in term and late preterm infants.

Objectives: The aim of our study was to determine both the impact and time course of C. difficile colonization in a cohort of very low birth weight infants (VLBWI) in an era of PCR-based technologies for diagnosis.

Methods: Stool samples of VLBWI were analyzed for the presence of C. difficile strains in regular intervals during the hospital stay by PCR ribotyping. Analysis was continued throughout the first 2 years of life.

Results: A 32% C. difficile colonization rate during the first 2 years of life and an in-hospital colonization rate of 8% was found in a cohort of 190 VLBWI. C. difficile colonization occurred mainly in the first 6 months of life, which was similar to term neonates. In-hospital colonization accounted for only a small percentage of cases with no detection of hypervirulent strains. Also, C. difficile colonization was not related to an adverse outcome in this VLBWI cohort. Oral lactoferrin of bovine origin and treatment with piperacillin/tazobactam were negatively correlated with C. difficile colonization in our study.

Conclusions: C. difficile colonization in our cohort of VLBWI was significantly lower than has been described in the literature and was not related to an adverse outcome.
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http://dx.doi.org/10.1159/000488025DOI Listing
September 2019

Arterial tortuosity syndrome: 40 new families and literature review.

Genet Med 2018 10 11;20(10):1236-1245. Epub 2018 Jan 11.

Pediatrics Department, Kuwait University, Kuwait City, Kuwait.

Purpose: We delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10.

Methods: We retrospectively characterized 40 novel ATS families (50 patients) and reviewed the 52 previously reported patients. We performed histology and electron microscopy (EM) on skin and vascular biopsies and evaluated TGF-β signaling with immunohistochemistry for pSMAD2 and CTGF.

Results: Stenoses, tortuosity, and aneurysm formation are widespread occurrences. Severe but rare vascular complications include early and aggressive aortic root aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric perforation. Thus far, no reports unequivocally document vascular dissections or ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome (IRDS) are frequently observed. Skin and vascular biopsies show fragmented elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a fragmented elastin core and a peripheral mantle of microfibrils of random directionality. Skin and end-stage diseased vascular tissue do not indicate increased TGF-β signaling.

Conclusion: Our findings warrant attention for IRDS and diaphragmatic hernia, close monitoring of the aortic root early in life, and extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific abnormalities.
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http://dx.doi.org/10.1038/gim.2017.253DOI Listing
October 2018

Runx2 mediated Induction of Novel Targets ST2 and Runx3 Leads to Cooperative Regulation of Hypertrophic Differentiation in ATDC5 Chondrocytes.

Sci Rep 2017 12 20;7(1):17947. Epub 2017 Dec 20.

Department of Neurosurgery, Medical University Graz, Graz, Austria.

Knowledge concerning expression and function of Suppression of Tumorigenicity 2 (ST2) in chondrocytes is at present, limited. Analysis of murine growth plates and ATDC5 chondrocytes indicated peak expression of the ST2 transmembrane receptor (ST2L) and soluble (sST2) isoforms during the hypertrophic differentiation concomitant with the expression of the hypertrophic markers Collagen X (Col X), Runx2 and MMP-13. Gain- and loss-of-function experiments in ATDC5 and primary human growth plate chondrocytes (PHCs), confirmed regulation of ST2 by the key transcription factor Runx2, indicating ST2 to be a novel Runx2 target. ST2 knock-out mice (ST2-/-) exhibited noticeable hypertrophic zone (HZ) reduction in murine growth plates, accompanied by lower expression of Col X and Osteocalcin (OSC) compared to wild-type (WT) mice. Likewise, ST2 knockdown resulted in decreased Col X expression and downregulation of OSC and Vascular Endothelial Growth Factor (VEGF) in ATDC5 cells. The ST2 suppression was also associated with upregulation of the proliferative stage markers Sox9 and Collagen II (Col II), indicating ST2 to be a new regulator of ATDC5 chondrocyte differentiation. Runx3 was, furthermore, identified as a novel Runx2 target in chondrocytes. This study suggests that Runx2 mediates ST2 and Runx3 induction to cooperatively regulate hypertrophic differentiation of ATDC5 chondrocytes.
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http://dx.doi.org/10.1038/s41598-017-18044-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738421PMC
December 2017

Bisphosphonates in multicentric osteolysis, nodulosis and arthropathy (MONA) spectrum disorder - an alternative therapeutic approach.

Sci Rep 2016 Sep 30;6:34017. Epub 2016 Sep 30.

Clinic for Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.

Multicentric osteolysis, nodulosis and arthropathy (MONA) spectrum disorder is a rare inherited progressive skeletal disorder caused by mutations in the matrix metalloproteinase 2 (MMP2) gene. Treatment options are limited. Herein we present successful bisphosphonate therapy in three affected patients. Patients were treated with bisphosphonates (either pamidronate or zoledronate) for different time periods. The following outcome variables were assessed: skeletal pain, range of motion, bone densitometry, internal medical problems as well as neurocognitive function. Skeletal pain was dramatically reduced in all patients soon after initiation of therapy and bone mineral density increased. Range of motion did not significantly improve. One patient is still able to walk with aids at the age of 14 years. Neurocognitive development was normal in all patients. Bisphosphonate therapy was effective especially in controlling skeletal pain in MONA spectrum disorder. Early initiation of treatment seems to be particularly important in order to achieve the best possible outcome.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043187PMC
http://dx.doi.org/10.1038/srep34017DOI Listing
September 2016

Breast milk feeding in infants with inherited metabolic disorders other than phenylketonuria - a 10-year single-center experience.

J Perinat Med 2017 Apr;45(3):375-382

University Hospital Innsbruck, Department of Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Anichstrasse. 35, A-6020 Innsbruck.

Background: Published data on breast milk feeding in infants suffering from inherited metabolic disorders (IMDs) other than phenylketonuria (PKU) are limited and described outcome is variable.

Objective: We aimed to evaluate retrospectively whether breastfeeding and/or breast milk feeding are feasible in infants with IMDs including organic acidemias, fatty acid oxidation disorders, urea cycle disorders, aminoacidopathies or disorders of galactose metabolism.

Methods: Data on breastfeeding and breast milk feeding as well as monitoring and neurological outcome were collected retrospectively from our database of patients with the mentioned IMD, who were followed in our metabolic center within the last 10 years.

Results: Twenty patients were included in the study, who were either breast fed on demand or received expressed breast milk. All the infants were evaluated clinically and biochemically at 2-4-week intervals, with weight gain as the leading parameter to determine metabolic control. Good metabolic control and adequate neurological development were achieved in all patients but one, who experienced the only metabolic crisis observed within the study period.

Conclusion: Breast milk feeding with close clinical and biochemical monitoring is feasible in most IMD and should be considered as it offers nutritional and immunological benefits.
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http://dx.doi.org/10.1515/jpm-2016-0205DOI Listing
April 2017

A novel therapeutic approach for LPIN1 mutation-associated rhabdomyolysis--The Austrian experience.

Muscle Nerve 2015 Sep 24;52(3):437-9. Epub 2015 Jul 24.

Department of Pediatrics, Clinic for Pediatrics I, Medical University of Innsbruck, Anichstrasse 35, A-6020, Innsbruck, Austria.

Introduction: Lipin 1 gene (LPIN1) mutations lead to cellular energy deficiency and cause up to 50% of the rhabdomyolysis episodes seen in pediatric patients. These episodes are associated with poor prognosis, as treatment options have been limited. We propose a novel therapeutic strategy based on prevention and early treatment of catabolism.

Methods: Five patients were diagnosed with LPIN1 mutations. They were instructed to maintain high caloric intake in situations possibly leading to catabolism such as viral infections or excessive physical activity. When an episode of rhabdomyolysis occurred, patients were treated with intravenous high-concentration glucose at first symptoms.

Results: The therapeutic strategies described limited the number of rhabdomyolyis episodes, and the duration of episodes was reduced from 7-10 days, as reported in the literature, to 5 days.

Conclusion: In this small series, patients with LPIN1 mutations appear to have benefited from prevention and early treatment of catabolism.
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http://dx.doi.org/10.1002/mus.24749DOI Listing
September 2015

ALG8-CDG: novel patients and review of the literature.

Orphanet J Rare Dis 2015 Jun 12;10:73. Epub 2015 Jun 12.

Medical University of Innsbruck, Clinic for Pediatrics I, Inherited Metabolic Disorders, Anichstrasse 35, 6020, Innsbruck, Austria.

Background: Since 1980, about 100 types of congenital disorders of glycosylation (CDG) have been reported representing an expanding group of inherited disorders. ALG8-CDG (= CDG-Ih) is one of the less frequently reported types of CDG, maybe due to its severe multi-organ involvement with coagulation disturbances, edema, massive gastrointestinal protein loosing enteropathy, cataracts, and often early death. We report three additional patients, provide an update on two previously reported, and summarize features of ten patients reported in literature.

Results: Of 15 ALG8-CDG patients, three were homozygous and 12 compound heterozygous. There were multiple prenatal abnormalities in 6/12 patients. In 13/15, there were symptoms at birth, 9/15 died within 12 months. Birth weight was appropriate in 11/12, only one was small for gestational age. Prematurity was reported in 7/12. Hydrops fetalis was noticed in 3, edemas in 11/13; gastrointestinal symptoms in 9/14; structural brain pathology, psychomental retardation, seizures, ataxia in 12/13, muscle hypotonia in 13/14. Common dysmorphic signs were: low set ears, macroglossia, hypertelorism, pes equinovarus, campto- and brachydactyly (13/15). In 10/11, there was coagulopathy, in 8/11 elevated transaminases; thrombocytopenia was present in 9/9. Eye involvement was reported in 9/14. CDG typical skin involvement was reported in 8/13.

Conclusion: In ALG8-CDG, isoelectric focusing of transferrin in serum or plasma shows an abnormal sialotransferrin pattern. The diagnosis is confirmed by mutation analysis in ALG8; all patients reported so far had point mutations or small deletions. The prognosis is generally poor. Thus, a timely and correct diagnosis is important for counselling.
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http://dx.doi.org/10.1186/s13023-015-0289-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504351PMC
June 2015

Ameliorative effects of PACAP against cartilage degeneration. Morphological, immunohistochemical and biochemical evidence from in vivo and in vitro models of rat osteoarthritis.

Int J Mol Sci 2015 Mar 13;16(3):5922-44. Epub 2015 Mar 13.

Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia 87, 95123 Catania, Italy.

Osteoarthritis (OA); the most common form of degenerative joint disease, is associated with variations in pro-inflammatory growth factor levels, inflammation and hypocellularity resulting from chondrocyte apoptosis. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide endowed with a range of trophic effects in several cell types; including chondrocytes. However; its role in OA has not been studied. To address this issue, we investigated whether PACAP expression is affected in OA cartilage obtained from experimentally-induced OA rat models, and then studied the effects of PACAP in isolated chondrocytes exposed to IL-1β in vitro to mimic the inflammatory milieu of OA cartilage. OA induction was established by histomorphometric and histochemical analyses. Changes in PACAP distribution in cartilage, or its concentration in synovial fluid (SF), were assessed by immunohistochemistry and ELISA. Results showed that PACAP abundance in cartilage tissue and SF was high in healthy controls. OA induction decreased PACAP levels both in affected cartilage and SF. In vitro, PACAP prevented IL-1β-induced chondrocyte apoptosis, as determined by MTT assay; Hoechst staining and western blots of apoptotic-related proteins. These changes were also accompanied by decreased i-NOS and COX-2 levels, suggesting an anti-inflammatory effect. Altogether, these findings support a potential role for PACAP as a chondroprotective agent for the treatment of OA.
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http://dx.doi.org/10.3390/ijms16035922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394513PMC
March 2015

Extra-virgin olive oil diet and mild physical activity prevent cartilage degeneration in an osteoarthritis model: an in vivo and in vitro study on lubricin expression.

J Nutr Biochem 2013 Dec;24(12):2064-75

Mediterranean diet includes a relatively high fat consumption mostly from monounsaturated fatty acids mainly provided by olive oil, the principal source of culinary and dressing fat. The beneficial effects of olive oil have been widely studied and could be due to its phytochemicals, which have been shown to possess anti-inflammatory properties. Lubricin is a chondroprotective glycoprotein and it serves as a critical boundary lubricant between opposing cartilage surfaces. A joint injury causes an initial flare of cytokines, which decreases lubricin expression and predisposes to cartilage degeneration such as osteoarthritis. The aim of this study was to evaluate the role of extra-virgin olive oil diet and physical activity on inflammation and expression of lubricin in articular cartilage of rats after injury. In this study we used histomorphometric, histological, immunocytochemical, immunohistochemical, western blot and biochemical analysis for lubricin and interleukin-1 evaluations in the cartilage and in the synovial fluid. We report the beneficial effect of physical activity (treadmill training) and extra-virgin olive oil supplementation, on the articular cartilage. The effects of anterior cruciate ligament transection decrease drastically the expression of lubricin and increase the expression of interleukin-1 in rats, while after physical activity and extra-virgin olive oil supplemented diet, the values return to a normal level compared to the control group. With our results we can confirm the importance of the physical activity in conjunction with extra-virgin olive oil diet in medical therapy to prevent osteoarthritis disease in order to preserve the articular cartilage and then the entire joint.
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http://dx.doi.org/10.1016/j.jnutbio.2013.07.007DOI Listing
December 2013

Cellular reactions to biodegradable magnesium alloys on human growth plate chondrocytes and osteoblasts.

Int Orthop 2014 Apr 21;38(4):881-9. Epub 2013 Nov 21.

Department of Orthopaedic Surgery, Medical University of Graz, Auenbruggerplatz 5, 8036, Graz, Austria,

Purpose: In recent decades operative fracture treatment using elastic stable intramedullary nails (ESINs) has mainly taken precedence over conservative alternatives in children. The development of biodegradable materials that could be used for ESINs would be a further step towards treatment improvement. Due to its mechanical and elastic properties, magnesium seems to be an ideal material for biodegradable implant application. The aim of this study was therefore to investigate the cellular reaction to biodegradable magnesium implants in vitro.

Methods: Primary human growth plate chondrocytes and MG63 osteoblasts were used for this study. Viability and metabolic activity in response to the eluate of a rapidly and a slower degrading magnesium alloy were investigated. Furthermore, changes in gene expression were assessed and live cell imaging was performed.

Results: A superior performance of the slower degrading WZ21 alloy's eluate was detected regarding cell viability and metabolic activity, cell proliferation and morphology. However, the ZX50 alloy's eluate induced a favourable up-regulation of osteogenic markers in MG63 osteoblasts.

Conclusions: This study showed that magnesium alloys for use in biodegradable implant application are well tolerated in both osteoblasts and growth plate chondrocytes respectively.
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http://dx.doi.org/10.1007/s00264-013-2163-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971266PMC
April 2014

Towards a better understanding of bone bridge formation in the growth plate - an immunohistochemical approach.

Connect Tissue Res 2013 26;54(6):408-15. Epub 2013 Aug 26.

Department of Orthopaedic Surgery, Medical University of Graz , Graz , Austria and.

The growth plate at the end of long bones is the cartilaginous organ responsible for longitudinal bone growth in children. Trauma to the growth plate, i.e. fractures, can severely impair longitudinal bone growth, leading to growth disorders due to destruction of the epiphyseal circulation and formation of a bone bridge. From the clinical experience it is known that in some patients this bone bridge eventually disappears during the growth process. However, the molecular mechanisms involved in bone bridge formation and dissolution have not been clarified yet. The aim of this study was to investigate the spatial and temporal protein level of molecules potentially involved in these processes, i.e. RANKL, OPG, DKK-1, Coll 10, BMP-2 and IL-6, in an experimental rat model using an immunohistochemical approach. The results from our study suggest that bone bridge formation might be an early event starting immediately after growth plate injury and involving several pro-osteoblastic molecules, i.e. IL-6, BMP-2 as well as OPG and Coll X. In the late studied time points 3- and 9-month post-injury expression of anti-osteoblastic proteins, i.e. DKK1 and RANKL, was increased. This indicates that bone bridge dissolution might be a late event and potentially linked to Wnt signaling inhibition and RANK/RANKL signaling activation.
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http://dx.doi.org/10.3109/03008207.2013.828715DOI Listing
June 2014

Post-traumatic caspase-3 expression in the adjacent areas of growth plate injury site: a morphological study.

Int J Mol Sci 2013 Jul 29;14(8):15767-84. Epub 2013 Jul 29.

Department of Bio-Medical Sciences, Human Anatomy and Histology Section, University of Catania, Catania 95123, Italy.

The epiphyseal plate is a hyaline cartilage plate that sits between the diaphysis and the epiphysis. The objective of this study was to determine the impact of an injury in the growth plate chondrocytes through the study of histological morphology, immunohistochemistry, histomorphometry and Western Blot analyses of the caspase-3 and cleaved PARP-1, and levels of the inflammatory cytokines, Interleukin-6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α), in order to acquire more information about post-injury reactions of physeal cell turnover. In our results, morphological analysis showed that in experimental bones, neo-formed bone trabeculae-resulting from bone formation repair-invaded the growth plate and reached the metaphyseal bone tissue (bone bridge), and this could result in some growth arrest. We demonstrated, by ELISA, increased expression levels of the inflammatory cytokines IL-6 and TNF-α. Immunohistochemistry, histomorphometry and Western Blot analyses of the caspase-3 and cleaved PARP-1 showed that the physeal apoptosis rate of the experimental bones was significantly higher than that of the control ones. In conclusion, we could assume that the inflammation process causes stress to chondrocytes that will die as a biological defense mechanism, and will also increase the survival of new chondrocytes for maintaining cell homeostasis. Nevertheless, the exact stimulus leading to the increased apoptosis rate, observed after injury, needs additional research to understand the possible contribution of chondrocyte apoptosis to growth disturbance.
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http://dx.doi.org/10.3390/ijms140815767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759885PMC
July 2013

The modified Harrington procedure for metastatic peri-acetabular bone destruction.

Int Orthop 2013 Oct 12;37(10):1981-5. Epub 2013 Jun 12.

Department of Orthopaedic Surgery, Medical University of Graz, Auenbruggerplatz 5, 8036, Graz, Austria,

Purpose: We describe the outcome in a series of patients treated for metastatic peri-actetabular and iliac bone destruction using a modified technique of Harrington's procedure.

Methods: Between 2006 and 2012, nine patients with a mean age of 62.2 years (42-75 years) were treated using a modified Harrington technique. Thereby, total hip replacement implants augmented by two to three threaded pins and cement were used to restore bony continuity of the pelvis and to achieve a stable construction allowing immediate full-weight bearing mobilisation.

Results: Acetabular destruction was graded according to Harrington's classification of peri-acetabular metastatic destruction, as class IV in one case, class III in six, and class II in two cases. The pre-operative ASA score ranged from II-IV. There were no intra-operative deaths or major complications such as excessive haemorrhage, deep infections, lesions of the femoral nerve, loss of fixation, or dislocations at final follow-up. Eight patients achieved an improvement of their functional status postoperatively. One reconstruction required revision and four patients died due to their underlying disease ten to 36 months after surgery.

Conclusion: We found this technique an effective, reproducible, and long-lasting method to relieve pain and improve or restore function in patients with destructive metastatic lesions of the peri-acetabular bone and the iliac wing. Although we performed surgery even in severely ill patients with extended, generalised metastatic disease we had no intra- or postoperative death and observed no major complications.
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http://dx.doi.org/10.1007/s00264-013-1940-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779553PMC
October 2013

Application and surgical technique of total knee arthroplasties: a systematic comparative analysis using worldwide registers.

Int Orthop 2013 Aug 24;37(8):1465-9. Epub 2013 May 24.

Department of Orthopaedic Surgery, Medical University of Graz, Auenbruggerplatz 5, 8036, Graz, Austria.

Purpose: The aim of this study was to compare total knee arthroplasty (TKA) procedures between different countries with regard to epidemiological data and surgical technique by reference to the worldwide arthroplasty registers.

Methods: A systematic search was carried out using the EFORT website to identify the relevant arthroplasty registers. We extracted data with respect to the number of implanted TKAs, patients' age distribution, procedure types, and revision rates. After identification of 28 national arthroplasty registers, 11 offered sufficient data regarding the above mentioned parameters and were therefore included in the final analysis.

Results: A large variation was found in the annual number of primary TKA implantations per inhabitant with a reported range from 30 to 199 per 100,000 (mean 106). The fixation method varied strongly between the different registers as well, e.g. 90 % of totally cemented TKAs in Sweden, England and Wales, Slovakia, and New Zealand versus 54 % cemented fixation in Australia. Another significant difference between included countries was observed with respect to the use of patellar resurfacing in TKA. Whilst the Danish knee arthroplasty register reports a percentage of 72 % using a patellar button in TKA the register from Norway reports only a minority of 2 %.

Conclusions: The comparison of arthroplasty registers revealed large differences regarding the annual number of primary TKAs per inhabitant and primary TKA procedure types. These variations may be explained by several factors such as patient demographics (prevalence of osteoarthritis) and national conditions such as healthcare systems (insurance status), number or availability of performing surgeons, medical facilities and surgeon-dependent factors such as definition of indications, education, tradition and experience.
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http://dx.doi.org/10.1007/s00264-013-1933-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728400PMC
August 2013

RANKL is downregulated in bone cells by physical activity (treadmill and vibration stimulation training) in rat with glucocorticoid-induced osteoporosis.

Histol Histopathol 2013 09 4;28(9):1185-96. Epub 2013 Apr 4.

Department of Pediatric and Adolescent Surgery, Medical University of Graz, Austria.

The aim of this study was to investigate bone tissue and plasma levels of RANKL and OPG in rats with prednisolone-induced osteoporosis and to evaluate the outcomes of physical activity on the skeletal system by treadmill and vibration platform training. Osteoporosis is a disease characterised by low bone mass and structural deterioration of bone tissue leading to bone fragility. Vibration exercise is a new and effective measure to prevent muscular atrophy and osteoporosis. The animals were divided into 5 groups. 1: control rats; 2: rats with osteoporosis receiving prednisolone; 3: rats receiving prednisolone and treadmill training; 4: rats receiving prednisolone and vibration stimulation training; 5: rats receiving prednisolone, treadmill and vibration stimulation training. For bone evaluations we used whole-body scans, histology and histomorphometric analysis. RANKL and OPG expression was evaluated by immunohistochemistry and biochemical analysis. After treatment, our data demonstrated that RANKL expression was significantly increased in groups 2 and 3 and decreased in groups 4 and 5. Conversely, OPG expression was significantly decreased in groups 2 and 3 and increased in groups 4 and 5. In conclusion, our findings suggest that mechanical stimulation inhibits the activity of RANKL. This finding provides new insights into the occurrence and progression of osteoporosis.
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http://dx.doi.org/10.14670/HH-28.1185DOI Listing
September 2013

The effects of physical activity on apoptosis and lubricin expression in articular cartilage in rats with glucocorticoid-induced osteoporosis.

J Bone Miner Metab 2013 May 22;31(3):274-84. Epub 2012 Dec 22.

Department of Bio-Medical Sciences, Human Anatomy and Histology Section, University of Catania, Catania, Italy.

Glucocorticoids are considered the most powerful anti-inflammatory and immunomodulating drugs. However, a number of side-effects are well documented in different diseases, including articular cartilage, where increases or decreases in the synthesis of hormone-dependent extracellular matrix components are seen. The objective of this study has been to test the effects of procedures or drugs affecting bone metabolism on articular cartilage in rats with prednisolone-induced osteoporosis and to evaluate the outcomes of physical activity with treadmill and vibration platform training on articular cartilage. The animals were divided into 5 groups, and bone and cartilage evaluations were performed using whole-body scans and histomorphometric analysis. Lubricin and caspase-3 expression were evaluated by immunohistochemistry, Western blot analysis and biochemical analysis. These results confirm the beneficial effect of physical activity on the articular cartilage. The effects of drug therapy with glucocorticoids decrease the expression of lubricin and increase the expression of caspase-3 in the rats, while after physical activity the values return to normal compared to the control group. Our findings suggest that it might be possible that mechanical stimulation in the articular cartilage could induce the expression of lubricin, which is capable of inhibiting caspase-3 activity, preventing chondrocyte death. We can assume that the physiologic balance between lubricin and caspase-3 could maintain the integrity of cartilage. Therefore, in certain diseases such as osteoporosis, mechanical stimulation could be a possible therapeutic treatment. With our results we can propose the hypothesis that physical activity could also be used as a therapeutic treatment for cartilage disease such as osteoarthritis.
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http://dx.doi.org/10.1007/s00774-012-0414-9DOI Listing
May 2013

BMP-6 and BMPR-1a are up-regulated in the growth plate of the fractured tibia.

J Orthop Res 2013 Mar 23;31(3):357-63. Epub 2012 Oct 23.

Department of Paediatric and Adolescence Surgery, Medical University of Graz, Auenbruggerplatz 34, 8036 Graz, Austria.

Bone overgrowth is a known phenomenon occurring after fracture of growing long bones with possible long-term physical consequences for affected children. Here, the physeal expression of bone morphogenetic proteins (BMPs) was investigated in a fracture-animal model to test the hypothesis that a diaphyseal fracture stimulates the physeal expression of these known key regulators of bone formation, thus stimulating bone overgrowth. Sprague-Dawley rats (male, 4 weeks old), were subjected to a unilateral mid-diaphyseal tibial fracture. Kinetic expression of physeal BMP-2, -4, -6, -7, and BMP receptor-1a (BMPR-1a) was analyzed in a monthly period by quantitative real time-polymerase chain reaction and immunohistochemistry. On Days 1, 3, 10, and 14 post-fracture, no changes in physeal BMPs gene-expression were detected. Twenty-nine days post-fracture, when the fracture was consolidated, physeal expression of BMP-6 and BMPR-1a was significantly upregulated in the growth plate of the fractured and contra-lateral intact bone compared to control (p<0.005). This study demonstrates a late role of BMP-6 and BMPR-1a in fracture-induced physeal growth alterations and furthermore, may have discovered the existence of a regulatory "cross-talk" mechanism between the lower limbs whose function could be to limit leg-length-discrepancies following the breakage of growing bones.
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http://dx.doi.org/10.1002/jor.22238DOI Listing
March 2013

Behaviour of human physeal chondro-progenitorcells in early growth plate injury response in vitro.

Int Orthop 2012 Sep 25;36(9):1961-6. Epub 2012 May 25.

Department of Pediatric and Adolescent Surgery, Medical University Graz, Auenbruggerplatz 34, 8036 Graz, Austria.

Purpose: The aim of this study was to investigate the proliferation and differentiation behaviour of a defined cell population gained from the human growth plate, namely, chondro-progenitorcells (CPCs), in the initial inflammatory phase of growth plate injury response in vitro.

Methods: Growth plate cells were sorted via FACS and differentiated along adipogenic and osteogenic lineage to confirm their progenitor features. To mimic the inflammatory phase of injury response at the growth plate they were treated with IL-1β and exposed to cyclic mechanical loading. A BrdU assay was used to investigate CPC proliferation. CPC differentiation behaviour was analysed by RT-PCR.

Results: CPCs (CD45-, CD34-, CD73+, CD90+, and CD105+) showed a successful differentiation along adipogenic and osteogenic lineage. Under conditions simulating the inflammatory phase of injury response at the growth plate in vitro CPCs differentiated towards hypertrophy while chondrogenesis and ossification were inhibited. Proliferation was not significantly altered.

Conclusion: This study showed that CPCs can be isolated from the human growth plate and expanded in vitro. In the first phase of injury response at the growth plate these cells differentiate towards hypertrophy. As longitudinal growth is obtained by chondrocyte proliferation and volume increase during hypertrophy this maturation might be the first step towards post-traumatic growth disorders such as unwanted premature ossification of the growth plate.
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http://dx.doi.org/10.1007/s00264-012-1578-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427442PMC
September 2012
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