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Biomedical subjects

K Aalto

Publications and source records attributed to K Aalto.

At least 19 recordsLinked to original sources

Lactate inhibits germ cell apoptosis in the human testis.

Dysregulation of male germ cell apoptosis has been associated with the pathogenesis of male infertility. Therefore, factors involved in the regulation of germ cell death are being actively investigated. Here, we studied the effects of lactate on human male germ cell death, using as a model a testis tissue culture in which physiological contacts are maintained between the germ cells and the supportive somatic Sertoli cells. Apoptosis of spermatocytes, spermatids and a few spermatogonia was induced by culturing segments of seminiferous tubules under serum-free conditions. This germ cell death was inhibited effectively and dose-dependently by lactate, indicating that it plays a crucial role in controlling cell death cascades of male germ cells. Interestingly, the anti-apoptotic role of lactate was not associated with changes in testicular adenine nucleotide (ATP, ADP and AMP) levels. In the seminiferous tubules, the final site of the death-suppressing action of lactate appeared to be downstream along the cell death pathway activated by the Fas receptor of the germ cells. In conclusion, testicular cell death was effectively regulated by lactate, which may be regarded as a potential compound for optimizing in-vitro methods involving male germ cells for assisted reproduction.

Adenine↗

Operative versus closed treatment of primary dislocation of the patella. Similar 2-year results in 125 randomized patients.

To assess whether initial surgery is beneficial for patients with primary dislocation of the patella, we carried out a prospective randomized study. Knee stability was examined under anesthesia, and associated injuries were excluded by diagnostic arthroscopy. 55 patients then had closed treatment and 70 patients were operated on with individually adjusted proximal realignment procedures. Surgery gave no benefit based on 2 years of follow-up. The subjective result was better in the non-operative group in respect of mean Houghston VAS knee score (closed 90, operative 87), but similar in terms of the patient's own overall opinion and mean Lysholm II knee score. Recurrent instability episodes (redislocation or recurrent subluxation) occurred in 20 nonoperated and in 18 operated patients. Of these, 15 and 12, respectively, then suffered redislocations. Function was better after closed treatment. Serious complications occurred after surgery in 4 patients. In conclusion, the recurrence of patellar dislocation may be more frequent than reported, whatever the form of treatment. Routine operative management cannot be recommended for primary dislocation of the patella.

Adolescent↗

Intracellular high energy metabolite depletion and cell membrane injury with antioxidant enzymes during oxidant exposure in vitro.

We compared oxidant-induced intracellular adenine nucleotide catabolism and cell membrane injury in 4 different human cell types. Responses to oxidant exposure were correlated with endogenous antioxidant enzyme activities in these cells. Blood monocytes, amniotic fibroblasts, umbilical vein endothelial cells in primary culture, and transformed bronchial epithelial cells (BEAS 2B) were exposed to 0.1-5 mM hydrogen peroxide (H2O2) for 4 h. Some experiments were conducted in cells pretreated with 3-amino 1:2,4-triazole (ATZ) to inactivate catalase or with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to inactivate glutathione (GSH) reductase. Depletion of adenine nucleotides and accumulation of their catabolic products (hypoxanthine, xanthine and uric acid) occurred to varying extent, monocytes being the most resistant. There was a mutual relationship between catalase and GSH reductase activities and maintenance of cellular adenine nucleotide levels during H2O2 exposure. GSH reductase inhibition rendered BEAS 2B cells susceptible to lytic injury by H2O2, assessed by release of lactate dehydrogenase and intact nucleotides into the medium, there was no correlation between these markers of such injury and endogenous antioxidant enzymes. We conclude that adenine nucleotide depletion and nucleotide catabolite accumulation relate closely with the antioxidant enzyme activities, whereas the lack of a similar correlation between the enzyme levels and markers of lytic cell injury suggest that intracellular antioxidant enzymes do not protect cells from membrane damage due to extracellular oxidants.

Adenine Nucleotides↗

Mitochondrial superoxide dismutase induction does not protect epithelial cells during oxidant exposure in vitro.

The significance of manganese superoxide dismutase (MnSOD) induction in cells and tissues during oxidant stress is still poorly understood. In this study, transformed human bronchial epithelial cells (BEAS 2B) were treated with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), or with combination of these cytokines (10 ng/ml concentrations) for 48 or 72 h and exposed to selected oxidants. TNF-alpha and IFN-gamma + TNF-alpha combination resulted in a marked increase of MnSOD protein and MnSOD activity. When cells pretreated with the cytokines were exposed to hyperoxia (95% O2, 72 h), menadione (5-50 microM, 4 h), or H2O2 (0.5 and 5 mM, 4 h), in all cases IFN-gamma and TNF-alpha enhanced oxidant-related cell injury. The effect was most significant with cells pretreated with a combination of IFN-gamma and TNF-alpha. Antioxidant enzymes such as total SOD, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase did not change significantly during the cytokine treatment. Catalase activity was not changed by IFN-gamma or TNF-alpha but it decreased significantly (34%) in IFN-gamma + TNF-alpha-treated cells. Free radical generation was not changed by these cytokines in acute (30 min) experimental conditions or after 48-h treatment. These results suggest that cytokine-induced MnSOD does not protect bronchial epithelial cells against endogenously or exogenously generated oxidants in vitro. In fact, cells that contained the highest MnSOD activity were the most sensitive to subsequent oxidant damage.

Bronchi↗

Cytotoxicity of oxidants and asbestos fibers in cultured human mesothelial cells.

The authors investigated the mechanisms caused by oxidants (superoxide and hydrogen peroxide) and asbestos (amosite) fibers in human mesothelial cells. Immortalized human pleural mesothelial cells (MET 5A) were exposed in vitro to one of the following: hypoxanthine (100-200 microM) plus xanthine oxidase (10-20 mU/ml) as a superoxide-generating system, H2O2 (50 microM-5 mM); or amosite (1-100 micrograms/cm2). Cellular adenine nucleotide depletion, DNA single strand breaks, extracellular release of nucleotides, and their catabolites and lactate dehydrogenase (LDH) were assessed as markers of cell damage after 4-6 h exposure to the oxidants or fibers. The effect of intracellular antioxidant enzymes and exogenous antioxidants on cell damage were investigated during oxidant and amosite exposure. Superoxide radical and H2O2 exposure resulted in the depletion of adenine nucleotides, accumulation of the products of nucleotide catabolism, induction of DNA single strand breaks, and extracellular LDH release. Amosite exposure did not cause nucleotide depletion or induction of DNA single strand breaks. Inactivation of the intracellular antioxidant enzymes glutathione reductase or catalase augmented cell damage during H2O2 exposure but not during amosite exposure.

Adenine Nucleotides↗

High hydrostatic pressures in traumatic joints require elevated synovial capillary pressure probably associated with arteriolar vasodilatation.

Three out of the four Starling pressures were determined at arthroscopy of traumatic effusions of the knee. The range of the joint fluid hydrostatic pressure Pjoint was 5-83 cmH2O (0.5-8.1 kPa, 4-61 mmHg), that of the colloid osmotic pressure difference COPplasma-COPjoint 0-21.7 cmH2O. In 11 of 15 cases the sum Pjoint+COP difference exceeded 32.6 cmH2O (3.19 kPa, 24 mmHg), a high estimate of average capillary pressure at the level of the heart. The number of 'exceeding' cases was 8/15 if only 80% of the COP difference was considered effective. Pjoint and the COP difference oppose filtration of fluid from plasma into joints, indicating that mean capillary pressure, the only Starling pressure not determined, was elevated unless the effusions were being resorbed back into the blood. The findings can be explained by tamponade compensated by arteriolar vasodilatation, suspected to be metabolically mediated.

Adolescent↗

Distraction bone healing.

Bone formation by distraction was studied using three different experimental models: (1) Physeal distraction of the sheep radius was performed in 20 animals. (2) Distraction after osteotomy of the radius was carried out in 39 sheep. (3) Mandibular distraction after osteotomy was performed in 17 sheep. Formation of the organic matrix and osteogenesis were studied by radiographic, histologic, and biochemical methods as well as by electron microscopy. The mode of osteogenesis was essentially similar in all of these distraction models. Bone formation was preceded by organization of the collagenous matrix in the distraction area. In the beginning of the distraction, the gap was composed of a heterogeneous cell population, with large polymorphic fibroblast-like cells. The cells in the central part differentiated into fibroblasts, which remained functionally active as long as distraction proceeded. During physeal distraction, bone formed from the epiphyseal and metaphyseal sides as well as from the surrounding perichondrium. Also, in osteotomy distraction of both tubular bone and mandible, bone formed centripetally from the osteotomized bone ends toward the center of the gap. The organic matrix was composed almost solely of Type I collagen in the earliest stages, suggesting that the mode of osteogenesis differs from bone repair by fracture callus. The structure of the distracted segment was mainly lamellar trabecular. Corticalization of the lengthened bone segment occurred gradually after several months.

Animals↗

Collagen synthesis and mineralization in the early phase of distraction bone healing.

Corticotomy of the distal radius followed by gradual distraction by external fixation was performed on three sheep. Collagen synthesis and mineral deposition were analysed from sequential biopsies obtained from the center of the distraction area during the first 4 weeks of distraction. The whole distraction area was rapidly filled with organic matrix the amount of which, due to fluctuation in its nonprotein component, initially decreased from 88 to 66% of the level in control bone but gained its initial level in 4 weeks. Total protein in the matrix represented 70% of that in the control bone during the 4-week follow up period while the proportion of collagen of the total protein increased from 53 to 88%, a level comparable with the unoperated bone. Determination of the type of fibrillar collagen by characterization of their cyanogen bromide peptides showed that in the distraction area production of type II collagen does not occur but the heteropolymer type I (alpha 1(I)2 alpha 2(I)1) collagen represents almost totally the collagen synthesized. Deposition of mineral into the distraction gap was detectable already after 2 weeks and increased rapidly after 3 weeks of distraction. The results suggest that unlike in other processes, e.g., direct osteonal and callus-type bone repair, in distraction bone healing gradual distraction of osteotomized bone leads directly to synthesis of mature fibrous organic matrix of bone followed by its rapid mineralization.

Animals↗

Experimental lengthening of tibial diaphysis: gap healing with or without gradual distraction.

Stepwise distraction of the rabbit tibia after a transverse diaphyseal osteotomy was performed in an external fixator. The goal was to clarify the fine-structural parameters of long-bone lengthening. The tibias were vertically cut and studied 5 weeks after the osteotomy, and the specimens with an initial gap without further lengthening were compared with those with a gap and stepwise distraction. The role of periosteal bone induction was essential for the ossification of a growing gap, whereas the ossification of a simple gap proceeded equally by the endosteal and periosteal routes. The distraction resulted in vertical organization of the premature callus tissue at the proximal pole of the distracted gap, while the distal part of the gap area was deficiently filled by endosteal bone but preliminary fixed by a bridge of periosteal callus tissue.

Animals↗

Fracture repair during external fixation. Torsion tests of rabbit osteotomies.

Bone repair was studied in the rabbit tibiofibular bone after a midshaft transverse osteotomy stabilized by external fixation and heavy compression. Both subendosteal and subperiosteal callus formation with concomitant contact healing were observed within 3 weeks, and were further succeeded by subendosteal resorption and increased porosis resulting in atrophy of the cortical bone. Subjected to the torsion test, the bones exhibited restoration of strength within 3 weeks, with maximal energy absorption and elasticity at 6 weeks. The failure of the osteotomy in the torsion test, with radiographic visibility of the osteotomy, characterized the soft-tissue type of behavior of the bones. Hard-tissue like behaviour of the bones with resistance to torsion at the osteotomy site and radiographic obliteration of the osteotomy line occurred by 12 weeks, indicating complete union of the osteotomy. Our experiments demonstrate that elastic external fixation is preferable to the rigid compression plate.

Animals↗

Structural changes in intact tubular bone after application of axial loads by external fixation.

The effects of external fixation on bone structure were studied in the intact tibiofibular bone of the rabbit using three types of fixation; distractive, compressive and neutralizing. In the diaphyseal bone subperiosteal new bone formation was noted after three weeks in all fixation types. This formation was succeeded by endosteal resorption and porotic transformation of the cortical bone. An ultimate result was a widening of the medullary cavity. Torsion tests revealed weakening of the bone specimens as an end result. Axial loads, either compressive or distracting had no additional effect on the bone changes observed.

Animals↗

Pin-hole changes after external fixation of tubular bone.

K-wire-pin-induced changes in cortical bone were studied in the intact rabbit tibiofibular bone. Using a bilateral external fixator two pairs of pins were applied under compression (10 kp), under distraction (10 kp), and in a neutralization sense. After defined intervals the pin-holes were investigated macroscopically and radiologically. Reactive and resorptive changes were present in 101 of 576 (17.5%) pin-holes, infection in 13 (2.3%) pin-holes. Changes were significantly more frequent in the distal pin-holes. The appearance of the pin-holes was not influenced by the type of external fixation used nor did the occurrence depend on the duration of metal implantation.

Animals↗

Total rupture of pectoralis major muscle in athletes.

Total rupture of the pectoralis major muscle is rare. It may follow a severe trauma or strenuous athletic exercise or performance. Five cases of total rupture of the pectoralis major muscle treated in athletes are reported. Two of them had made an extremely exerted effort in weight lifting, one was injured during a parachute landing, one was tackled in an ice hockey match, and one injured his pectoralis major muscle while pushing himself up from a swimming pool. In two cases the diagnosis was made early and in three cases 2-4 months after the injury. All of the patients were male and were treated successfully with surgery. Later they were able to exercise their sports. The weight lifters did not go on with competitive sports.

Adult↗

Fever, C-reactive protein, and erythrocyte sedimentation rate in monitoring recovery from septic arthritis: a preliminary study.

Body temperature, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were measured sequentially in nine children less than 11 years old during their recovery from culture-positive septic arthritis (SA). The measurements were compared with those of two other children who recovered without antibiotic therapy. A clinical investigation carried out several months after discharge suggested permanent recovery in all cases, including the spontaneously recovered patients. Defervescence and normalization of the primarily elevated CRP and ESR values occurred in a similar manner in both groups. On average, fever lasted 5 days, CRP level decreased below 20 mg/L in 7 days, and ESR reached a value of less than or equal to 20-25 mm/h in 22 days. The normalization time of ESR differed highly significantly (p less than 0.001) both from the duration of fever and from the normalization time of CRP level. Because CRP behaved in a similar manner in both the medicated and the nonmedicated groups, its normalization suggests true extinction of the active inflammatory process. If so, CRP level may be of benefit in monitoring the duration of antibiotic therapy for SA, but the hypothesis has to be confirmed in a larger clinical trial.

Anti-Bacterial Agents↗

Articular cartilage after meniscectomy. Rabbit knees studied with the scanning electron microscope.

Ten rabbits had a medial meniscectomy in both knees. The articular surface was studied with a scanning electron microscope 2, 4 or 12 weeks after the operation. Three sham operated and two unoperated rabbits served as controls. Progressive articular cartilage damage was observed on the weight-bearing areas of the medial condyles. The findings are compatible with clinical observations after meniscectomy; they confirm that meniscectomy is not a harmless operation.

Animals↗

Blood flow in rabbit osteotomies studied with radioactive microspheres.

Arterial embolisation with radio-active microspheres was used to measure the proportion of cardiac output to the skeleton and the tibiofibular bone both in unoperated rabbits and in rabbits after tibial osteotomy and subsequent external fixation. The mean uptake of the intact tibiofibula was 0.11 per cent of the cardiac output and, correspondingly, 0.21 per cent after the osteotomy. Maximal uptake occurred 18 days after the operation which was accompanied by a slight decrease in overall skeletal circulation.

Animals↗