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Biomedical subjects

T A Järvinen

Publications and source records attributed to T A Järvinen.

At least 19 recordsLinked to original sources

Effect of 4-min vertical whole body vibration on muscle performance and body balance: a randomized cross-over study.

The purpose of this randomized cross-over study was to investigate the effects of a 4-min long, 2-mm vertically-vibrating vibration-exercise on muscle performance and body balance in healthy subjects. Sixteen volunteers (eight men and women aged 18-35 years) underwent both the 4-min vibration- and sham-interventions in a randomized order on different days. Performance- and balance-tests (stability platform, grip strength, extension strength of lower extremities, tandem-walk, vertical jump and shuttle-run) were done 10 minutes before (baseline) and 2 and 60 minutes after the intervention. In addition, the effect of vibration on the surface electromyography (EMG) of soleus, vastus lateralis, gluteus medius, and paravertebralis muscles was investigated during the vibration. The 4-min vibration-loading did not induce any statistically significant change in the performance- or balance-tests at the 2- or 60-min tests. Interestingly, however, the mean power frequency of the EMG in the vastus lateralis and gluteus medius muscles decreased during the vibration-intervention, indicating muscle fatigue, particularly in the hip region. It was concluded that a 4-min long, 2-mm vertically-vibrating vibration-stimulus did not induce changes in the performance and balance tests. Future studies should focus on evaluating the effects of different kinds of vibration-regimens, as well as the long-term effects of vibration-training, on body balance and muscle performance, and, as a broader objective, on bone.

Adolescent↗

Achilles tendon injuries.

The Achilles tendon is the strongest tendon in the human body. Because most Achilles tendon injuries take place in sports and there has been an common upsurge in sporting activities, the number and incidence of the Achilles tendon overuse injuries and complete ruptures have increased in the industrialized countries during the last decades. The most common clinical diagnosis of Achilles overuse injuries is tendinopathy, which is characterized by a combination of pain and swelling in the Achilles tendon accompanied by impaired ability to perform strenuous activities. Most patients with Achilles tendon injury respond favorably to conservative treatment and only those who fail to respond to carefully followed nonoperative treatment should undergo surgery for repair. A complete rupture of the Achilles tendon usually occurs in sports that require jumping, running, and quick turns. Although histopathologic studies have shown that ruptured Achilles tendons include clear degenerative changes before the rupture, many of the Achilles tendon ruptures occur suddenly without any preceding signs or symptoms. Neither conservative nor operative treatment is a treatment of choice for the ruptured Achilles tendon. It is generally accepted that surgery should be performed on ruptured Achilles tendons in young, physically active patients and in those patients for whom the diagnosis or the treatment of the rupture has been delayed, whereas the results of conservative treatment are an acceptable outcome in older patients with sedentary lifestyles. Many important issues still remain unanswered concerning the cause, pathogenesis, diagnosis, and management of the Achilles tendon disorders. Only when these issues have been solved by well-controlled studies can tailored treatment protocols be created.

Achilles Tendon↗

Predictors of biological aggressiveness of prostate specific antigen screening detected prostate cancer.

PURPOSE: It is not known whether screening of asymptomatic men with prostate specific antigen (PSA) decreases the mortality of prostate cancer. We evaluated the extent to which PSA screening identifies clinically significant prostate cancer by analyzing markers of biological aggressiveness. MATERIALS AND METHODS: We compared prostate cancer in 56 patients in the screening and 21 in the randomized control arm of a population based cohort of 8,975 men 55 to 67 years old participating in the Finnish arm of the European Randomized Study of Screening for Prostate Cancer to 47 clinically detected organ confined, 30 clinically detected metastatic and 16 latent prostate tumors identified at autopsy in 46 consecutive subjects. Biological aggressiveness was determined by histological grading using the Gleason and Mostofi scales, tumor proliferation rate by Ki-67 immunostaining, p53 over expression by immunostaining and aneuploidy by fluorescence in situ hybridization using formalin fixed, paraffin embedded tumor specimens. RESULTS: A total of 56 neoplasms were detected in 2,781 men (2%) who participated in PSA screening and 21 were detected in 5,975 nonscreened controls (0.35%) during the study period. Disease in nonscreened controls more often involved a high tumor proliferation rate (p = 0.004) and p53 over expression (p = 0.015) than screening detected disease. At least 1 feature of biological aggressiveness was present in 19% of latent, 34% of screening detected, 51% of clinically detected and organ confined, 62% of randomized control and 87% of metastasis cases. Of the screening detected tumors defined as biologically aggressive 74% were identified at organ confined stages pT1-2N0M0. CONCLUSIONS: PSA screening detects a significant number of biologically aggressive cancers at an early clinical stage, implying that screening may decrease mortality.

Aged↗

Vitamin D and estrogen receptor polymorphisms and bone mineral changes in postpartum women.

BsmI restriction fragment length polymorphism (RFLP) of the vitamin D receptor (VDR) gene and PvuII RFLPs of the estrogen receptor (ER) gene and their relation to changes in areal bone mineral density (BMD) were examined in 43 healthy postpartum Finnish women aged 31.3 (SD 4.7) years. BMD was measured by dual energy X-ray absorptiometry at lumbar spine, right femoral neck, and dominant distal radius immediately after delivery, 1 month after resumption of menses, and 1 year thereafter. The RFLPs were represented as Bb (BsmI) and Pp (PvuII), the capital letters denoting the absence of and the small letters the presence of the restriction sites. The frequency of VDR alleles was as follows: bb (20.9%), Bb (60.5%), and BB (18.6%), and that of ER alleles was pp (39.5%), Pp (51.2%), and PP (9.3%). Altogether, BMD decreased significantly during postpartum amenorrhea at all sites [the mean bone loss ranging from -1.2 (SD 3.6)% at the distal radius to -3.7 (2.9)% at the femoral neck], and increased after resumption of menses [the 1-year follow-up BMD values ranging from -1.0 (2.4)% at the femoral neck to +3.3 (4.0)% at the lumbar spine as compared with baseline]. No obvious genotype-related differences were found between these changes. These results suggest that the BsmI and PvuII polymorphisms may not have substantial influence on BMD changes postpartum.

Adult↗

Estrogen receptor beta is coexpressed with ERalpha and PR and associated with nodal status, grade, and proliferation rate in breast cancer.

The role of estrogen (ER) and progesterone receptors (PR) in breast cancer is well established. Identification of the second human estrogen receptor, the estrogen receptor beta (ERbeta), prompted us to evaluate its role in breast cancer. We studied the expression of ERbeta by immunohistochemistry and mRNA in situ hybridization in 92 primary breast cancers and studied its association with ERalpha, PR, and various other clinicopathological factors. Sixty percent of tumors were defined as ERbeta-positive (nuclear staining in >20% of the cancer cells). Normal ductal epithelium and 5 of 7 intraductal cancers were also found to express ERbeta. Three-fourths of the ERalpha- and PR-positive tumors were positive for ERbeta, whereas ERalpha and PR were positive in 87% and 67% of ERbeta-positive tumors, respectively. ERbeta was associated with negative axillary node status (P < 0.0001), low grade (P = 0.0003), low S-phase fraction (P = 0.0003), and premenopausal status (P = 0.04). In conclusion, the coexpression of ERbeta with ERalpha and PR as well as its association with the other indicators of low biological aggressiveness of breast cancer suggest that ERbeta-positive tumors are likely to respond to hormonal therapy. The independent predictive value of ERbeta remains to be established.

Adult↗

Amplification and deletion of topoisomerase IIalpha associate with ErbB-2 amplification and affect sensitivity to topoisomerase II inhibitor doxorubicin in breast cancer.

Topoisomerase IIalpha (topoIIalpha) is a key enzyme in DNA replication and a molecular target for many anti-cancer drugs called topoII inhibitors. The topoIIalpha gene is located at chromosome band 17q12-q21, close to the ErbB-2 oncogene (HER-2/neu), which is the most commonly amplified oncogene in breast cancer. Because of the physical proximity to ErbB-2, copy number aberrations may also occur in the topoIIalpha gene. These topoIIalpha gene copy number aberrations may be related to the altered chemosensitivity to topoII inhibitors that breast cancers with ErbB-2 amplification are known to have. We used fluorescence in situ hybridization to study copy number aberrations of both topoIIalpha and ErbB-2 in nine breast cancer cell lines and in 97 clinical breast tumors, which were selected for the study according to their ErbB-2 status by Southern blotting. TopoIIalpha-protein expression was studied with Western blot and sensitivity to doxorubicin (a topoII inhibitor) with a 96-well clonogenic in vitro assay. Two of the five cell lines with ErbB-2 gene amplification (SK-BR-3 and UACC-812) showed amplification of topoIIalpha. In MDA-361 cells, ErbB-2 amplification (14 copies/cell) was associated with a physical deletion of topoIIalpha (four copies of chromosome 17 centromere and two copies of topoIIalpha). The topoIIalpha amplification in UACC-812 cells was associated with 5.9-fold-increased topoIIalpha protein expression and 2.5-fold-increased sensitivity to the topoII inhibitor, doxorubicin, whereas the deletion in MDA-361 leads to decreased protein expression (45% of control) and a 2.4-fold-increased chemoresistance in vitro. Of 57 ErbB-2-amplified primary breast carcinomas, 25 (44%) showed ErbB-2-topoIIalpha coamplification and 24 (42%) showed a physical deletion of the topoIIalpha gene. No topoIIalpha copy number aberrations were found in 40 primary tumors without ErbB-2 amplification. TopoIIalpha gene amplification and deletion are common in ErbB-2-amplified breast cancer and are associated with increased or decreased sensitivity to topoII inhibitors in vitro, respectively. These findings may explain the altered chemosensitivity to topoII inhibitors reported in ErbB-2-amplified breast cancers.

Antigens, Neoplasm↗

Tenascin-C in the pathobiology and healing process of musculoskeletal tissue injury.

Tenascin-C (TN-C) is a hexabrachion-shaped extracellular matrix (ECM) protein which has very restricted expression in normal musculoskeletal tissues, but is expressed in large quantities in these tissues during embryogenesis as well as during regenerative and healing processes. TN-C is an elastic protein which has a number of binding sites for other extracellular matrix proteins as well as for cell membrane adhesion receptors. In addition, it can be stretched to several times its resting length, the ability of which is attributed to the stretch-induced unfolding of its fibronectin type III domains. In the musculoskeletal tissues, TN-C is present in the regions where high mechanical forces are transmitted from one tissue component to another, such as the myotendinous and osteotendinous junctions. Not surprisingly, it was recently presented that the expression of TN-C in the musculoskeletal tissues is regulated by the mechanical strain applied to their cells. Thus, taking into account the flexible structure of the TN-C and its site-specific expression pattern at sites exposed to heavy mechanical loads, TN-C is likely to play an important role in providing elasticity to the musculoskeletal tissues. This feature has a special significance in the degenerative and regenerative processes where the normal biomechanical environment of the musculoskeletal tissue is temporarily interrupted by injury. The rapidly increasing understanding of the structure and function of the ECM protein TN-C may well bring important insights into the clinical treatment of sports injuries in the future.

Animals↗

High topoisomerase IIalpha expression associates with high proliferation rate and and poor prognosis in oligodendrogliomas.

The role of molecular markers predicting the prognosis and the selection of patients for further adjuvant therapies is not well established in oligodendroglioma patients. A potential prognostic as well as a therapeutically predictive factor, topoisomerase IIalpha (topoIIalpha), is a molecular target for certain cytotoxic drugs. Its expression has been shown to correlate with the prognosis in a number of different cancers and with the chemosensitivity of cancer cells in vitro. The expression of topoIIalpha was evaluated immunohistochemically in 59 oligodendrogliomas and in 29 mixed gliomas with a predominating oligodendroglioma component by the use of a tissue microarray technique. In the gliomas, the percentage of topoIIalpha immunopositive cells protein expression varied from 0.0 to 49.1% (5.2 +/- 8.3%, mean+/- SD). In oligoastrocytomas, the mean topoIIalpha score was significantly higher in the oligodendroglioma than in the astrocytoma component of the tumour (5.37 +/- 5.58% vs. 1.89 +/- 2.49%, P = 0.018). A significant association was found between the high proportion of topoIIalpha positive cells and high grade of the tumour (P < 0.0001), high tumour proliferation rate (P < 0.0001), p53 overexpression (P = 0.01) and high expression of tumour suppressing retinoblastoma protein (P = 0.023). TopoIIalpha expression was not associated with the age or sex of patient, and the rate of apoptosis. TopoIIalpha expression associated highly significantly with patient prognosis; a significantly higher proportion of patients with low rather than with high topoIIalpha score was alive at the end of the 5-year follow-up (P = 0.03). Cox analysis was used to demonstrate that topoIIalpha had an independent prognostic value for survival (P = 0.034). In conclusion, high topoIIalpha expression characterizes oligodendrogliomas and oligoastrocytomas which are poorly differentiated, have high proliferation rate, and has prognostic value for overall survival of these patients. Therefore, topoIIalpha may be a useful marker for better targeted selection of poor prognosis oligodendroglioma patients for adjuvant therapy.

Adolescent↗

Muscle strain injuries.

Muscle injuries--lacerations, contusions or strains--are by far the most common injuries in sports. After first aid following the RICE principle (Rest, Ice, Compression and Elevation), therapy must be tailored according to the severity of the injury and based on the knowledge gained from experimental studies on regeneration of injured muscle. Most muscle injuries can be treated conservatively with excellent recovery, but complete ruptures with complete loss of function should be managed surgically. Immediately after the injury, a short period of immobilization is needed to accelerate formation of the scar between the stumps of the ruptured myofibers, to which the stumps adhere. The optimal length of immobilization depends on the grade of the injury, and should not be longer than needed for the scar to bear the pulling forces without rerupture. Early mobilization is required to invigorate adhesion, orientation of the regenerating muscle fibers, revascularization and resorption of the connective tissue scar. Another important aim of early mobilization, especially in clinical sports medicine, is to minimize inactivity-induced atrophy as well as loss of strength and extensibility, which are rapidly appearing adverse sequelae of prolonged immobilization.

Athletic Injuries↗

Mechanical loading regulates tenascin-C expression in the osteotendinous junction.

Elastic extracellular matrix protein tenascin-C (TN) has very restricted expression in normal tissues, but is expressed in large quantities during embryogenesis and hyperplastic processes. To examine the importance of mechanical stress on the regulation of TN expression in vivo, the effects of various mechanical loading states (immobilization and three forms of subsequent remobilization) on the expression of TN were studied immunohistochemically at the bone-tendon attachment of the rat quadriceps muscle. This osteotendinous junction (OTJ) was selected as study site, since it receives its mechanical stimuli only from muscle contracting activity, which is easy to block by cast immobilization. TN was expressed abundantly in the normal OTJ. Following the removal of the mechanical stress from the junction by cast-immobilization of three weeks, the immunoreactivity of TN was almost completely absent. Normal mechanical stress in the form of free remobilization of eight weeks (free cage activity) resulted in a slight increase in TN expression, but could not restore the expression of TN to the level of the healthy contralateral leg. After the application of the increased mechanical stress (intensified remobilization of the eight weeks by low- or high-intensity treadmill running), the distribution and immunoreactivity of TN reached the level of the healthy contralateral limb in the low-intensity running group or even exceeded that in the high-intensity running group. High TN expression was seen around the chondrocytes and fibroblasts of the OTJ as well as around the collagen fibers of the tendon belly. We conclusively show that mechanical strain regulates the expression of TN in vivo, and propose that mechanical stress is a major regulator of TN expression in fibroblasts and chondrocytes. This may be an important aspect of the regulation of TN expression during embryogenesis, tendon degeneration, wound healing, bone formation, and in the other normal or regenerative morphogenetic processes TN is postulated to take part in.

Animals↗

Characterization of topoisomerase II alpha gene amplification and deletion in breast cancer.

Topoisomerase IIalpha (TOP2A) is a key enzyme in DNA replication and a molecular target for many important anticancer drugs. TOP2A is amplified or deleted together with amplification of the closely located ERBB2/HER-2/neu oncogene in breast cancer. We characterized the copy number aberrations of TOP2A and ERBB2 in 136 primary breast tumors by FISH. Among the 70 primary tumors with ERBB2 amplification, amplification of TOP2A was found in 29 (41%); 30 tumors (43%) showed a physical deletion of TOP2A; and the copy number for TOP2A was not altered in 11 tumors with ERBB2 amplification (16%). No TOP2A gene aberrations were identified in 65 primary tumors without ERBB2 amplification. Fiber FISH revealed that simultaneously amplified ERBB2 and TOP2A were not present in the same amplicon, because repetitive tandem repeat-like signals of ERBB2 and TOP2A were in separate DNA fibers. The deletion of TOP2A (seen in the MDA-361 cell line and in 31 primary tumors) was interstitial, spanning less than two megabases of DNA. Mean copy numbers of TOP2A (2.4 +/- 0.6 for TOP2A vs. 4.9 +/- 1.1 for chromosome 17 centromere) suggest that the deletion of TOP2A occurs before polyploidization of the genome. Eight primary tumors with high-level ERBB2 amplification showed a new type of intratumoral heterogeneity; two different cell clones with either high-level amplification or deletion of TOP2A were found adjacent to each other in the same tumor. These results indicate that amplification of the ERBB2 oncogene is followed by complex secondary genetic aberrations, which lead to amplification or deletion of the TOP2A gene in a majority of tumors. Genes Chromosomes Cancer 26:142-150, 1999.

Antigens, Neoplasm↗

Vitamin D receptor alleles and bone's response to physical activity.

The objective of this prospective controlled study was to determine whether the osteogenic response of bone to mechanical loading is dependent on the vitamin D receptor (VDR) polymorphism. Thirty-five healthy premenopausal women took part in a progressive, high-impact exercise three times a week for a period of 18 months and 45 women served as nonexercising controls. The trainees were divided into three groups: bb (n = 12, 34%); Bb (n = 16, 46%); BB (n = 7, 20%) according to polymorphism at the gene encoding the VDR (BB representing subjects without the restriction enzyme BsmI sites on the two VDR gene alleles). Bone mineral content (BMC) and areal bone mineral density (BMD) were measured at the lumber spine, proximal femur, knee, calcaneus, and dominant distal radius before the beginning of the exercise regimen and at 12 and 18 months of training using dual-energy x-ray absorptiometry (DXA). As an indicator of the total osteogenic effect of the training, SigmaBMC was derived by summing up the BMC values of the loaded sites (i.e., the lower limb sites and the lumbar spine). The mean SigmaBMC increased 2.0% in the bb group, 3.0% in the Bb group, and 2.8% in the BB group (P = 0.184 for the intergroup difference), but only 0. 8% in the controls (exercisers versus controls, P < 0.001). Individuals with the BB genotype of the VDR gene, subjects with whom the BMC can be lower than normal and whose bones can be less responsive to pharmacological therapies than bones of the other individuals, seem to have as good osteogenic response to mechanical loading as subjects with other VDR genotypes. Thus, irrespective of the VDR genotype, physical activity seems to be beneficial for bones of premenopausal women.

Absorptiometry, Photon↗

Location and distribution of non-collagenous matrix proteins in musculoskeletal tissues of rat.

The study assessed immunohistochemically the location and distribution of various non-collagenous matrix proteins (fibronectin, laminin, tenascin-C, osteocalcin, thrombospondin-1, vitronectin and undulin) in musculoskeletal tissues of rat. Fibronectin and thrombospondin-1 were found to be ubiquitous in the studied tissues. High immunoreactivity of these proteins was found in the extracellular matrix of the anatomical sites where firm bindings are needed, i.e. between muscle fibres and fibre bundles, between the collagen fibres of a tendon and at myotendinous junctions, osteotendinous junctions and articular cartilage. Tenascin-C was found in the extracellular matrix of regions where especially high forces are transmitted from one tissue component to the other, such as myotendinous junctions and osteotendinous junctions. Laminin was demonstrated in the basement membranes of the muscle cells and capillaries of the muscle-tendon units. Osteocalcin immunoreactivity concentrated in the extracellular matrix of areas of newly formed bone tissue, i.e. in the subperiosteal and subchondral regions, osteoid tissue and mineralized fibrocartilage zone of the osteotendinous junction. Mild vitronectin activity could be seen in the extracellular matrix of the osteotendinous and myotendinous junctions, and high activity around the bone marrow cells. Undulin could be demonstrated in the extracellular matrix (i.e. on the collagen fibres) of the tendon and epimysium only. However, it was co-distributed with fibronectin and tenascin-C. Together, these findings on the normal location and distribution of these non-collagenous proteins in the musculoskeletal tissues help to form the basis of knowledge against which the location and distribution of the these proteins in various pathological processes could be compared.

Animals↗

Predictive value of topoisomerase IIalpha and other prognostic factors for epirubicin chemotherapy in advanced breast cancer.

Although cytotoxic chemotherapy is widely used in advanced breast cancer, there are no powerful predictors for the therapy response. Because topoisomerase IIalpha (Topo IIalpha) is the molecular target for the anthracycline class of anti-cancer drugs, we compared the immunocytochemical assay of Topo IIalpha with other biomarkers in the prediction of clinical response to Topo II inhibitor chemotherapy. Fifty-five patients with advanced breast cancer were treated with a single cytotoxic drug, Topo II-inhibitor, epirubicin (30 mg m(-2) weekly up to 1000 mg m(-2)), as first line cytotoxic chemotherapy. Objective response to treatment was analysed according to UICC criteria. The predictive value of Topo IIalpha expression, c-erbB2 oncoprotein, p53 tumour-suppressor protein, oestrogen (ER) and progesterone receptor (PR), S-phase fraction and DNA ploidy were analysed from representative formalin-fixed paraffin-embedded primary tumour samples. The proportion of Topo IIalpha-positive cells (Topo IIalpha index) failed to predict response to epirubicin therapy. Mean Topo IIalpha scores in 29 responding patients were similar when compared with those with no change in disease progression (n = 13) and those with progressive disease (n = 13) (14.9% +/- 11.4% vs 15.5% +/- 7.6% vs 17.3% +/- 13.2%, not significant). Among the other biomarkers tested, overexpression of c-erbB2 oncoprotein and hormone receptor negativity were significantly associated with poor response. Response rate in patients with c-erbB2-overexpressing tumours was 32% compared with 65% in patients with no c-erbB2 overexpression (P = 0.0058). Accordingly, the response rate for ER-positive patients was 67% compared with 26% in ER-negative patients (P = 0.0021). Although both negative ER status and c-erbB2 overexpression are associated with high Topo IIalpha expression in breast cancer, step-wise logistic regression analysis showed that ER and c-erbB2 were associated with therapy response independent of Topo IIalpha expression. Histological grade, p53, DNA-ploidy, tumour proliferation rate (S-phase fraction), stage of the disease at diagnosis, age of the patient, previous anti-oestrogen therapy or site of metastasis did not predict the response to epirubicin therapy. In conclusion, despite extensive in vitro evidence, expression of Topo IIalpha is unlikely to predict the response to Topo II inhibitor chemotherapy in advanced breast cancer. Among the prognostic biomarkers, overexpression of c-erbB2 oncogene and negative ER may have predictive value in epirubicin therapy in patients with advanced breast cancer.

Antibiotics, Antineoplastic↗

Free mobilization and low- to high-intensity exercise in immobilization-induced muscle atrophy.

After 3 wk of immobilization, the effects of free cage activity and low- and high-intensity treadmill running (8 wk) on the morphology and histochemistry of the soleus and gastrocnemius muscles in male Sprague-Dawley rats were investigated. In both muscles, immobilization produced a significant (P < 0.001) increase in the mean percent area of intramuscular connective tissue (soleus: 18.9% in immobilized left hindlimb vs. 3.6% in nonimmobilized right hindlimb) and in the relative number of muscle fibers with pathological alterations (soleus: 66% in immobilized hindlimb vs. 6% in control), with a simultaneous significant (P < 0.001) decrease in the intramuscular capillary density (soleus: mean capillary density in the immobilized hindlimb only 63% of that in the nonimmobilized hindlimb) and muscle fiber size (soleus type I fibers: mean fiber size in the immobilized hindlimb only 69% of that in the nonimmobilized hindlimb). Many of these changes could not be corrected by free remobilization, whereas low- and high-intensity treadmill running clearly restored the changes toward control levels, the effect being most complete in the high-intensity running group. Collectively, these findings indicate that immobilization-induced pathological structural and histochemical alterations in rat calf muscles are, to a great extent, reversible phenomena if remobilization is intensified by physical training. In this respect, high-intensity exercise seems more beneficial than low-intensity exercise.

Animals↗

Blood flow in rat gastrocnemius muscle and Achilles tendon after Achilles tenotomy.

The effect of Achilles tenotomy on resting blood flow of rat gastrocnemius muscle and Achilles tendon was studied by radioactive microspheres. Tenotomy produced an immediate, marked decrease in both intramuscular and intratendinous blood flow and it remained significantly lowered at both sites till the end of the observation period, i.e., day 18 after tenotomy. The decrease in the resting blood flow was more rapid and pronounced in the Achilles tendon than in the gastrocnemius muscle. Although the blood flow of the Achilles tendon started to recover after the 4th postoperative day, it was still 33% (statistically not significant) lower than that in the controls 18 days after tenotomy. In the gastrocnemius muscle, the 18-day deficit was 38% (p < 0.001), respectively. The results indicate that after division of a rat Achilles tendon the resting blood flow to the gastrocnemius muscle and Achilles tendon is not adequately restored, remaining at a significantly lowered level even 18 days after tenotomy.

Achilles Tendon↗

Number and morphology of mechanoreceptors in the myotendinous junction of paralysed human muscle.

The mechanoreceptor system of the myotendinous junction (MTJ) of human palmaris longus muscle obtained at autopsy was studied histologically from six patients with flaccid paralysis (complete acute tetraplegia 4-6 weeks before the autopsy, due to a spinal cord injury), eight patients with spastic paralysis (chronic hemiplegia due to cerebral stroke) and ten neurologically normal controls. Four types of nerve endings, Ruffini and Pacini corpuscles, Golgi tendon organs, and free nerve endings, could be identified in the MTJs of the controls. In the MTJs of the patients with flaccid and spastic paralysis, the free nerve endings were not present and the mechanoreceptors that were found were few in number, degenerated, fibrotic, and atrophic. These mechanoreceptors had lost their connection with the muscle fibres and tendon bundles and were frequently located within pathological accumulations of fatty tissue in the myotendinous region. The number and distribution of mechanoreceptors in the MTJ were almost identical in patients with flaccid and spastic paralysis.

Adult↗

Endogenous nitric oxide and prostaglandin E2 do not regulate the synthesis of each other in interleukin-1 beta-stimulated rat articular cartilage.

Increased levels of nitric oxide (NO) and prostaglandins (PG) are present in the synovial fluid from patients with rheumatoid arthritis and osteoarthritis. Interleukin-1 beta (IL-1) has been shown to induce the synthesis of both of these mediators. The present work was designed to study the interactions of NO and PGE2 synthesis induced by IL-1 in rat articular cartilage. Incubation of intact cartilage with IL-1 resulted in different dose response curves for NO and PGE2 synthesis. Two inhibitors of nitric oxide synthase N-monomethyl-L-arginine (L-NMMA) and L-N-iminoethylornithine, (L-NIO), abolished the IL-1-induced nitrite production but failed to have any influence on the PGE2 synthesis. Exogenous NO, produced by two chemically different NO-releasing compounds (SIN-1 and GEA 3175) had no effect on PGE2 synthesis in articular cartilage. Dexamethasone and ketoprofen inhibited IL-1 induced PGE2 production, while nitrite synthesis remained unaltered. Acetylsalicylic acid (ASA) reduced PGE2 synthesis and had a slight inhibitory action also on NO production. In conclusion, our results show, that IL-1 induces the synthesis of both PGE2 and NO in articular cartilage but these two inflammatory mediators are not mediating the synthesis of one another.

Animals↗