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Biomedical subjects

P Myllynen

Publications and source records attributed to P Myllynen.

At least 19 recordsLinked to original sources
PubMed2006

DNA damage caused by benzo(a)pyrene in MCF-7 cells is increased by verapamil, probenecid and PSC833.

The aim of this study was to clarify whether pharmaceutical drugs capable of inhibiting ABC-transporters affect the toxicity of benzo(a)pyrene (BP). MCF-7 breast adenocarcinoma cells were cultured for 24 and 48 h with benzo(a)pyrene (1 microM) and the transporter inhibitors verapamil (0.125-100 microM), PSC833 (0.05-5 microM) or probenecid (0.05-2 mM). DNA binding of benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE) was analyzed by synchronous fluorescence spectrophotometry and p53 protein by immunoblotting. BP metabolism was studied using thin layer chromatography (TLC). MTT assay and ATP quantitation were used for the analysis of cell viability. At 24 h there was no statistically significant increase in the DNA-adduct formation by any of the used inhibitors. However, at 48 h all of the inhibitors, in concentrations known to effectively block ABC transporters, increased the BPDE-DNA adduct formation 1.5 to 2-fold compared to adduct formation with BP only. PSC833 and verapamil also increased p53 protein expression at 48 h (p<0.05). Probenecid decreased glucuronidation of (3)H-BP metabolites. Other inhibitors did not decrease statistically significantly the overall formation of water-soluble metabolites. BP alone slightly decreased viability of cells at 48 h according to ATP quantitation as compared to vehicle treated controls (86.4+/-16.4%). Even though the used inhibitors showed some cytotoxicity, the combination of BP and inhibitors did not decrease cell viability in synergistic manner. According to these results certain pharmaceutical drugs may increase DNA damage caused by benzo(a)pyrene in MCF-7 cells at least partly through the inhibition of transporters. Taking into account the complex metabolism of BP and lack of specificity of the inhibitors used, it is likely that increased DNA damage seen in this study was the result of multiple interactions between the inhibitors, BP metabolism and the efflux of the compounds.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2005

Human placenta: a human organ for developmental toxicology research and biomonitoring.

Pregnant mothers are exposed to a wide variety of foreign chemicals. This exposure is most commonly due to maternal medication, lifestyle factors, such as smoking, drug abuse, and alcohol consumption, or occupational and environmental sources. Foreign compounds may interfere with placental functions at many levels e.g. signaling, production and release of hormones and enzymes, transport of nutrients and waste products, implantation, cellular growth and maturation, and finally, at the terminal phase of placental life, i.e. delivery. Placental responses may also be due to pharmaco-/toxicodynamic responses to foreign chemicals, e.g. hypoxia. On the other hand, placental xenobiotic-metabolizing enzymes can detoxify or activate foreign chemicals, and transporters either enhance or prevent cellular accumulation and transfer across the placenta. The understanding of what xenobiotics do to the placenta and what the placenta does to the xenobiotics should provide the basis for the use of placenta as a tool to investigate and predict some aspects of developmental toxicity. This review aims to give an update of the fate and behavior of xenobiotics in the placenta from the viewpoint of xenobiotic-metabolizing enzymes and transporters. Their response levels will be described according to gestational status and methods used. The effects of foreign chemicals on placental metabolizing enzymes will be discussed. Also, interactions in the transporter protein level will be covered. The role of the placenta in contributing to developmental effects and fetotoxicity will be examined. The toxicological effects of maternal medications, smoking, and environmental exposures (dioxins, pesticides) as well as some possibilities for biomonitoring will be highlighted.

Animals↗
PubMed2004

Factors associated with nonunion in conservatively-treated type-II fractures of the odontoid process.

In type-II fractures of the odontoid process, the treatment is either conservative in a halo vest or primary surgical stabilisation. Since nonunion, requiring prolonged immobilisation or late surgery, is common in patients treated in a halo vest, the identification of those in whom this treatment is likely to fail is important. We reviewed the data of 69 patients with acute type-II fractures of the odontoid process treated in a halo vest. The mean follow-up was 12 months. Conservative treatment was successful, resulting in bony union in 32 (46%) patients. Anterior dislocation, gender and age were unrelated to nonunion. However, nonunion did correlate with a fracture gap (> 1 mm), posterior displacement (> 5 mm), delayed start of treatment (> 4 days) and posterior redisplacement (> 2 mm). We conclude that patients presenting with these risk factors are unlikely to achieve bony union by treatment in a halo vest. They deserve careful attention during the follow-up period and should also be considered as candidates for primary surgical stabilisation.

Adolescent↗
PubMed2001

Transplacental passage of oxcarbazepine and its metabolites in vivo.

PURPOSE: The purpose of this study was to investigate human fetal exposure to oxcarbazepine (OCBZ) in vivo. METHODS: Transplacental passage and placental tissue concentrations of OCBZ and its metabolites were determined. Maternal venous blood, cord blood, and placental tissue samples from 12 mothers using OCBZ during pregnancy alone or in combination with other antiepileptic drugs were collected. Samples were analyzed with high-performance liquid chromatography. RESULTS: Maternal venous concentrations of OCBZ and its major metabolites were at same range as cord blood concentrations (OCBZ in maternal serum, 0.19 +/- 0.16 microg/ml, and in cord serum, 0.21 +/- 0.19 microg/ml; 10-hydroxy-10,11-dihydrocarbamazepine (10-OH-CBZ) in maternal serum, 5.69 +/- 2.49 microg/ml, and in cord serum, 5.23 +/- 1.44 microg/ml; 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine (10,11-D) in maternal serum, 0.29 +/- 0.22 microg/ml, and in cord serum, 0.28 +/- 0.14 microg/ml). OCBZ (0.17 +/- 0.16 microg/g placental tissue), 10-OH-CBZ (3.49 +/- 1.34 microg/g placental tissue) and 10,11-D (0.25 +/- 0.11 microg/g placental tissue) were detected in the placental tissue. The amount of OCBZ detected from placental tissue was 0.01% of the daily dose. CONCLUSIONS: OCBZ, like other antiepileptic drugs, is transferred significantly through the placenta in humans.

Adult↗
PubMed2001

Carbamazepine: a 'blind' assessment of CVP-associated metabolism and interactions in human liver-derived in vitro systems.

1. The ability of various in vitro systems for CYP enzymes (computer modelling, human liver microsomes, precision-cut liver slices, hepatocytes in culture, recombinant enzymes) to predict various aspects of in vivo metabolism and kinetics of carbamazepine (CBZ) was investigated. 2. The study was part of the EUROCYP project that aimed to evaluate relevant human in vitro systems to study drug metabolism. 3. CBZ was given to the participating laboratories without disclosing its chemical nature. 4. The most important enzyme (CYP3A4) and metabolic route (10,11-epoxidation) were predicted by all the systems studied. 5. Minor enzymes and routes were predicted to a different extent by various systems. 6. Prediction of a clearance class, i.e. slow clearance, was correctly predicted by microsomes, slices, hepatocytes and recombinant enzymes (CYP3A4). 7. The 10,11-epoxidation of CBZ by the recombinant CYP3A4 was enhanced by the addition of exogenous cytochrome-b5, leading to a considerable over-prediction. 8. Induction potency of CBZ was predicted in cultured hepatocytes in which 7-ethoxycoumarin O-deethylase was used as an index activity. 9. It seems that for a principally CYP-metabolized substance such as CBZ, all liver-derived systems provide useful information for prediction of metabolic routes, rates and interactions.

Anticonvulsants↗
PubMed2000

Conservative and operative treatment in cervical burst fractures.

The aim of this study is to compare the results of non-operative and anterior operative treatment of cervical burst and flexion teardrop fractures. Sixty-nine consecutive patients treated during 1980 to 1995 were reviewed retrospectively. Thirty-four of them had been treated with skull traction or halo-vest and 35 with anterior decompression, bone grafting and fixation by an anterior Caspar plate. Neurological functioning on admission and at the end of the follow-up was assessed by using Frankel's classification. Kyphosis and spinal canal encroachment by retropulsed fragments were measured radiographically. Operatively treated patients recovered more often with at least one Frankel grade (P = 0.027) and presented less narrowing of the spinal canal (P = 0.0006) and kyphotic deformity (P = 0.00003) at the end of the followup. In comparison with the conservative methods, the operative Caspar technique provided superior decompression and fixation as well as promoted the healing of cord injuries caused by burst and flexion teardrop fractures.

Adolescent↗
PubMed1999

Spinal cord injuries in ice hockey in Finland and Sweden from 1980 to 1996.

Traumatic spinal cord injury (SCI) in the cervical or thoracic region is one of the most catastrophic types of sport injuries. This study was designed to determine incidence and mechanisms of major SCI in ice hockey in Finland and Sweden from 1980 to 1996 in order to find possibilities for prevention. Retrospective analysis of injury occurrence were carried out. Medical case records were reviewed and injured players were interviewed to complete the data. From 1980 to 1996, there were 16 accidents involving spinal cord injury with permanent disability. All players were male. The mean age was 21.1 years (range = 14 to 33 yr). In 50% of the cases the mechanism was body checking from behind and a blow to the head from the boards. In 69% of the cases the vertebral injury was fracture or/and luxation between C5 and C7. The neurological endstate was tetraplegia/paresis in 10 cases and paraplegia/paresis of the lower extremities in 6 cases. Ice hockey is one of the most popular sports in Europe, and the number of participants is still increasing. The typical mechanism in SCI is body checking from behind, falling down and a head-first blow from the boards. These serious injuries may be prevented by changing the rules (banning body checking near the boards) with strict refereeing and education of trainers and players.

Adolescent↗
PubMed1998

Microsomal metabolism of carbamazepine and oxcarbazepine in liver and placenta.

Metabolism of both carbamazepine (CBZ) and oxcarbazepine (OCBZ) were catalyzed by human liver microsomes and microsomes from livers of CBZ-induced or non-induced C57BL/6 mice. Human placental microsomes metabolized only OCBZ. Mouse liver microsomes metabolized CBZ to carbamazepine-10,11-epoxide (CBZ-E), 10-hydroxy-10,11-dihydro-carbamazepine (10-OH-CBZ), 3hydroxy-carbamazepine (3-OH-CBZ), 10,11-trans-dihydroxy-10,11-dihydro-carbamazepine (10,11-D) and to an unidentified metabolite. CBZ-pretreatment of mice increased both ethoxyresorufin O-deethylase activity in the liver and the amount of CBZ-E in microsomal incubations regardless of the age of mice. Human liver microsomes catalyzed the formation of CBZ to 9-hydroxymethyl-10-carbamoyl acridan (9-AC) in addition to CBZ-E, 3-OH-CBZ and 10-OH-CBZ. OCBZ was metabolized to its active metabolite in all incubations. An unknown metabolite was also present in some of the incubations. Human liver microsomes catalyzed only minute covalent binding of CBZ and OCBZ to DNA. Binding of OCBZ was, however, one order of magnitude greater than binding of CBZ. Human placental microsomes from the mothers on CBZ therapy did not catalyze CBZ metabolism. The same microsomes catalyzed OCBZ metabolism to 10-OH-CBZ and to an unknown metabolite. These results indicate autoinduction in CBZ metabolism in mouse liver. Due to the higher binding of OCBZ than CBZ to DNA in vitro, further studies on the potential mutagenicity of OCBZ may be warranted.

Animals↗
PubMed1997

Complications of transpedicular lumbosacral fixation for non-traumatic disorders.

We analysed the complications encountered in 102 consecutive patients who had posterolateral lumbosacral fusion performed with transpedicular screw and rod fixation for non-traumatic disorders after a minimum of two years. Of these, 40 had spondylolysis and spondylolisthesis, 42 a degenerative disorder, 14 instability after previous laminectomy and decompression, and six pain after nonunion of previous attempts at spinal fusion without internal fixation. There were 75 multilevel and 27 single-level fusions. There were 76 individual complications in 48 patients, and none in the other 54. The complications seen were screw misplacement, coupling failure of the device, wound infection, nonunion, permanent neural injury, and loosening, bending and breakage of screws. Screw breakage or loosening was more common in patients with multilevel fusions (p < 0.001). Screws of 5 mm diameter should not be used for sacral fixation. Forty-six patients had at least one further operation for one or several complications, including 20 fusion procedures for nonunion. The high incidence of complications is a disadvantage of this technically-demanding method.

Adolescent↗
PubMed1996

Posterolateral lumbosacral fusion with transpedicular fixation: 63 consecutive cases followed for 4 (2-6) years.

We analyzed the clinical, vocational and radiologic outcomes of 63 consecutive posterolateral lumbosacral fusions performed with transpedicular fixation. The indication for surgery was long-standing intractable lumbar and/or radiating pain with spondylolysis-olisthesis in 31 cases, degenerative disc disease and/or facet joint arthrosis in 23 cases and pain after laminectomy/decompression in 9 cases. Radiographic union was finally achieved in 30 out of the 63 cases. Fixation device-related complications, such as screw misplacement, breakage, bending and loosening, occurred in 33 cases. 15 patients underwent refusion. 43 patients obtained good pain relief. There was no correlation between bony healing and a good clinical outcome. 28/49 preoperatively employed patients returned to work. There was no correlation between relief of pain and return to work. 20 patients retired on a full disability pension. The clinical results were best in the spondylolysis-olisthesis group. Only 2/15 patients with markedly reduced spondylolisthesis maintained the reduction. In 3 patients, progressive disc degeneration above the level of fusion was observed. We conclude that posterolateral lumbosacral fusion with transpedicular fixation provides a satisfactory clinical outcome in patients with spondylolysis-olisthesis, but the high incidence of complications related to the fixation device in the other indications studied is a serious drawback of the method.

Adolescent↗
PubMed1996

Return to work after posterolateral fusion with transpedicular instrumentation for spondylarthrosis of the lumbosacral spine.

We reviewed 41 working-age adults with lumbosacral spondylarthrosis treated by posterolateral spinal fusion using transpedicular instrumentation. The fusion indication was a long-standing, intractable low-back and/or radiating pain, resistant to conservative treatment, without any radiological evidence or disc herniation or spinal stenosis. All patients were evaluated for their post-treatment employment status. The patients were followed up until they had either returned to work or received a permanent disability pension. Only 15 patients out of 41 returned to work after an average postoperative sick leave of seven months. A proper selection of patients is mandatory when this kind of resource-consuming spinal surgery is practised.

Adult↗
PubMed1996

The effect of enoxaparin in prevention of deep venous thrombosis in hip and knee surgery--a comparison with the dihydroergotamine-heparin combination.

A randomized study was carried out in order to compare the low-molecular heparin enoxaparin to heparin-dihydroergotamine (HDHE) combination, as prophylactic anti-thrombotic measure in patients undergoing hip replacement or knee replacement surgery or fractures of the femoral neck. A total of 165 patients both female and male were included in the study. The patients were randomized into two treatment groups. One group was treated with heparin-dihydroergotamine 0.5 mg + 5,000 IU twice a day and the other with enoxaparin 40 mg once daily. All patients were examined with Doppler ultrasound on day 3-5 and after the termination of medication which was the end of the study. Positive Doppler ultrasound findings were confirmed either by duplex Doppler or phlebography and clinical signs of pulmonary embolism were confirmed by isotope scintigraphy. The overall incidence of thromboembolic events was low (3%). One deep venous thrombosis (DVT) was seen in the enoxaparin group and two cases of pulmonary embolism in the heparin-dihydroergotamine group. Thus, the two regimens showed comparable efficacy and the overall safety was comparable. However, enoxaparin caused significantly less injection site haematoma. Correspondingly, the size of the injection site haematoma was significantly smaller in the enoxaparin group.

Adult↗
PubMed1995

Acute injuries in soccer, ice hockey, volleyball, basketball, judo, and karate: analysis of national registry data.

OBJECTIVE: To determine the acute injury profile in each of six sports and compare the injury rates between the sports. DESIGN: Analysis of national sports injury insurance registry data. SETTING: Finland during 1987-91. SUBJECTS: 621,691 person years of exposure among participants in soccer, ice hockey, volleyball, basketball, judo, or karate. MAIN OUTCOME MEASURES: Acute sports injuries requiring medical treatment and reported to the insurance company on structured forms by the patients and their doctors. RESULTS: 54,186 sports injuries were recorded. Injury rates were low in athletes aged under 15, while 20-24 year olds had the highest rates. Differences in injury rates between the sports were minor in this adult age group. Overall injury rates were higher in sports entailing more frequent and powerful body contact. Each sport had a specific injury profile. Fractures and dental injuries were most common in ice hockey and karate and least frequent in volleyball. Knee injuries were the most common cause of permanent disability. CONCLUSIONS: Based on the defined injury profiles in the different sports it is recommended that sports specific preventive measures should be employed to decrease the number of violent contacts between athletes, including improved game rules supported by careful refereeing. To prevent dental injuries the wearing of mouth guards should be encouraged, especially in ice hockey, karate, and basketball.

Adolescent↗
PubMed1994

A controlled immunohistochemical study of inflammatory cells in disc herniation tissue.

STUDY DESIGN: The presence and abundance of inflammatory cells was studied immunocytochemically in lumbar disc herniations (DH) and macroscopically normal discs for comparison. OBJECTIVES: The objective of the study was to characterize inflammatory cells that appear in herniated disc tissue and to study the relative abundance of various types of inflammatory cells. SUMMARY OF BACKGROUND DATA: Only few macrophages were observed in control discs, whereas abundant macrophages were present in half of the DH. Other types of inflammatory cells were less often abundant in the present material. In about a third of the DH interleukin-1 beta-expressing cells were also observed. METHODS: Twenty-four DH and control tissue from five discs were studied immunocytochemically, using specific monoclonal antibodies to various types of inflammatory cells and interleukin-1 beta. The results were compared with corresponding clinical data. Macrophages were studied with an antibody to CD68 antigen and Ber-MAC3 antibody separately. RESULTS: The obtained results suggest a variable inflammatory cell response in DH, which seems to be often dominated by macrophages at the time of operation. Thus previous suggestions of sometimes very active inflammation in DH tissue are supported. CONCLUSIONS: Inflammation may be important in disc tissue pathophysiology, possibly also in discogenic pain mechanisms.

Adult↗
PubMed1993

The integrity of intervertebral disks after operative treatment of thoracolumbar fractures.

This study presents the results of magnetic resonance imaging (MRI) follow-up studies on 14 patients with unstable fractures of T12 or L1. Internal fixation was performed with Harrington rods in eight patients and with transpedicular fixation in six patients. Sixteen intervertebral disks adjacent to the fractured vertebral body in 11 patients showed decreased signal intensity in T2-weighted images. None of the uninjured intervertebral disks showed any detectable signal decrease in T2-weighted images. Temporary fixation of several healthy motion segments of thoracolumbar spine, as is necessary with Harrington instrumentation for 11 months, on average, does not seem to result in an intervertebral disk degeneration detectable on MRI in the patients within a follow-up period of two years.

Adolescent↗
PubMed1992

Platelet activation during acute phase after multiple trauma.

The acute phase after multiple trauma is associated with both thrombotic phenomena and a bleeding diathesis. To evaluate the activation of platelets, beta-thromboglobulin (BTG) in plasma and serum and thromboxane B2 (TxB2) in serum were measured in 14 patients with multiple trauma. BTG in plasma was significantly increased on days 1, 2 and 10 to 14 after the trauma. The highest median value 90 micrograms/l was measured on day 1. BTG in serum was significantly reduced 1 to 7 days after the trauma (median levels 4450-9100 micrograms/l). TxB2 was significantly reduced (median levels 18-97 ng/l) on days 1 to 14. The increased plasma levels of BTG is due to the posttraumatic activation of platelets in vivo. The reduced levels of serum BTG and TxB2 reflect the deficient functional capacity of circulating platelets to respond to extreme stress. Therefore, platelet count alone may correlate poorly with the haemostatic potential and may underestimate the need of platelet transfusions.

Acute-Phase Reaction↗