The response of heat shock proteins 25 and 72 to ischaemia in different kidney zones

 Induction of heat shock proteins (HSPs) following cell injury contributes to the protection of vital cell functions. It was, therefore, of interest to study the effects of transient renal ischaemia on the abundance and distribution of two HSPs, HSP25 and HSP72, in renal tissue using Western-blot techniques. Analyses were performed on the supernatant (HSP25, HSP72) and pellet (HSP25) of homogenates obtained from cortex (CX) and outer (OM) and inner (IM) medulla of the rat kidney immediately after 60 min of ischaemia followed by varying periods of reperfusion. Ischaemia of the left kidney caused HSP25 contents to decrease in CX, OM and IM by 73, 89 and 54% respectively, compared with the corresponding zones of the contralateral control kidney. This initial decrease in supernatant HSP25 was accompanied by an increased abundance of HSP25 in the pellet. Following reperfusion, HSP25 contents in the supernatant gradually increased in CX and OM, reaching, after 24 h, values that were 5.4- and 2.5-fold higher, respectively, than those in the control kidneys. After 7 or 14 days of reperfusion, HSP25 contents had not completely normalised in CX, but had reached control levels in OM. In IM, the HSP25 content remained below control throughout the entire reperfusion period. HSP72 (supernatant) was below the detection limit in the CX of the control kidney. Similar to the level of HSP25, that of HSP72 was also markedly lower in OM and IM immediately after ischaemia. The intrarenal distribution of HSP72 and the sequence of zonal changes in HSP72 contents were similar to those observed for HSP25. These results are compatible with the view that, during ischaemia and the initial reperfusion period, HSP25 migrates from the cytoplasmic compartment (supernatant) into the nucleus and/or associates with cytoskeletal structures. The observation that both HSP25 and HSP72 are transiently induced in CX and OM, but not in IM, may be explained by the fact that, while all kidney cells are exposed to ischaemic stress, only inner medullary cells experience a major postischaemic attenuation of osmotic stress. Received: 11 February 1997 / Received after revision and accepted: 26 March 1997     

Monoclonal antibodies to glycoproteins of Vinca alkaloid-resistant human leukemic cells

Drug resistance is a major problem in the successful treatment of cancer. Resistance to one drug is often associated with cross-resistance to other anticancer agents. This is commonly seen with the "natural product" anticancer drugs such as the Vinca alkaloids and anthracyclines. In experimental systems, specific changes in plasma membranes characterize this "multiple drug resistance." The most prominent of these is the enhanced expression in several systems of high-molecular-weight glycoproteins ranging from Mr approximately equal to 150,000 to approximately equal to 180,000, the amount of which has been shown to be related to the degree of drug resistance. We report here the production of three monoclonal antibodies that bind preferentially to the surfaces of cultured human leukemic lymphoblasts resistant to the Vinca alkaloid vinblastine. Each antibody recognizes a surface membrane glycoprotein with molecular weights of 180,000 to 210,000. Additionally, two of the antibodies also recognize a second surface glycoprotein with molecular weights of either approximately equal to 155,000 or approximately equal to 130,000. All of these glycoproteins are overexpressed in the alkaloid-resistant cells. While a Mr approximately equal to 180,000 protein has been shown to be associated with multiple drug resistance, the other two glycoproteins have not been described previously in these cells. These antibodies may be useful in studies of the mechanisms of drug resistance, as well as in screening cells from drug-resistant patients for these resistance-associated glycoproteins.     

Factors interfering with the 1 mg dexamethasone suppression test in depression

The 1 mg dexamethasone suppression test (DST) was performed in 50 depressive inpatients in order to investigate factors which might interfere with its sensitivity and specificity for endogenous depression: improvement within one week after the test, recent admission to a psychiatric ward, and weight loss. Four out of five endogenous depressive patients whose depression improved within one week after the test had normal suppression, thus supporting the assumption that normalization of the DST may precede the improvement in depression. Nonendogenous depressive patients had an accumulation of pathologic test results on the day after admission that may be due to "admission stress". However, in endogenous depressives this effect was not observed. An influence of weight loss on the percentage of suppressors and nonsuppressors was not demonstrable. It is concluded that in the evaluation of DST results time parameters should be considered to a greater degree.     

Rapid hydroxylation of methtryptoline (1-methyltetrahydro-β-carboline) in rat: Identification of metabolites by chiral gas chromatography-mass spectrometry

Summary Racemic methtryptoline (1-methyltetrahydro--carboline) and 5-hydroxymethtryptoline-9-carboxylic acid (6-hydroxy-1-methyltetrahydro--carboline-1-carboxylic acid) were administered intraperitoneally to rats and the components of their urine was subsequently investigated by chiral gas chromatography-mass spectrometry. Methtryptoline rapidly became hydroxylated in the 5- and 6-position and excreted in urine. There was about a ninefold predominance of the S(–) enantiomer over the other in the 5-hydroxylated species, while the 6-hydroxylation produced a small excess of the R(+) enantiomer. About 75% of the injected dose of methtryptoline was recovered in the urine as 5- and 6-hydroxylated compounds during the first 24 h period, demonstrating that hydroxylation represents the major metabolic pathway. Treatment with 6-hydroxymethtryptoline-9-carboxylic acid led to a fivefold increase in the urinary excretion of 5-hydroxymethtryptoline during the first 24 h period with a predominance of the S(–)-enantiomer, indicating a much smaller conversion rate than from methtryptoline. It was concluded that hydroxylation of methtryptoline is a likely pathway for the natural formation of 5-hydroxymethtryptoline.     

Differentiation and the multiple drug resistance phenotype in human leukemic cells

A common feature of mammalian cell lines selected for multiple drug resistance is the overexpression of a high-molecular-weight surface membrane glycoprotein(s). While its amount has been shown to be related to the degree of resistance of such cells, its function in this phenomenon remains obscure. Because there are some biochemical and functional similarities between drug-resistant cells and differentiated cells, we asked if resistance-associated glycoproteins were also associated with cellular differentiation. Using three monoclonal antibodies against antigens known to be associated with differentiation and three monoclonal antibodies that distinguish our multiple drug-resistant human leukemic CEM/VLB100 cells from their drug-sensitive counterparts, we found that the resistant cells were neither altered in their apparent state of differentiation nor were they altered in their ability to respond to a differentiation stimulus with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate. We did find, however, that one antibody that recognizes the resistance-associated glycoprotein, Mr 180,000 glycoprotein (gp180), was only minimally altered in amount bound after treatment with the phorbol ester, but two other resistance-associated glycoproteins, Mr 155,000 glycoprotein (gp155) and, to a lesser extent, Mr 130,000 glycoprotein (gp130), were reduced in expression after this treatment. We suggest that the function of the previously described "marker" glycoprotein associated with multiple drug resistance remains unknown, but that the expression of two other resistance-associated glycoproteins also appears to be related to cellular differentiation or maturation in these cells.     

Diet Quality of Elite Australian Athletes Evaluated Using the Athlete Diet Index

While athletes’ nutrient intakes have been widely reported, few studies have assessed the diet quality of athletes. This is the first study to evaluate the diet quality of athletes using the purpose-built Athlete Diet Index (ADI). A convenience sample of 165 elite athletes from Australian sporting institutions completed the ADI online, with subsequent automated results provided to their respective accredited sports dietitians (ASDs). At the completion of athlete participation, ASDs (n = 12) responded to a range of survey items using a Likert scale (i.e., 1 = strongly agree to 5 = strongly disagree) to determine the suitability of the ADI in practice. Differences in ADI scores for demographics and sport-specific variables were investigated using independent t-tests, analysis of variance (ANOVA) and Bonferroni multiple comparisons. Spearman’s rank correlation was used to assess the association between total scores and demographics. The mean total ADI score was 91.4 ± 12.2 (range 53–117, out of a possible 125). While there was no difference in total scores based on demographics or sport-specific variables; team sport athletes scored higher than individual sport athletes (92.7 vs. 88.5, p < 0.05). Athletes training fewer hours (i.e., 0–11 h/week) scored higher on Dietary Habits sub-scores compared with athletes training more hours (≥12 h/week; p < 0.05), suggesting that athletes who train longer may be at risk of a compromised dietary pattern or less than optimal nutrition practices that support training. Most (75%) ASDs surveyed strongly agreed with the perceived utility of the ADI for screening athletes and identifying areas for nutrition support, confirming its suitability for use in practice.     

A Comparison of Bone-Targeted Exercise With and Without Antiresorptive Bone Medication to Reduce Indices of Fracture Risk in Postmenopausal Women With Low Bone Mass: The MEDEX-OP Randomized Controlled Trial

The goal of the MEDEX-OP trial was to compare the efficacy of a known effective high-intensity resistance and impact training (HiRIT) with a low-intensity exercise control (Buff Bones® [BB]), alone or in combination with antiresorptive bone medication, on indices of fracture risk (bone mass, body composition, muscle strength, functional performance), compliance, and safety. Primary study outcomes were 8-month change in lumbar spine (LS) and total hip (TH) bone mineral density (BMD). Healthy postmenopausal women with low bone mass (T-score ≤ −1.0) on or off stable doses (≥12 months) of antiresorptive medication were recruited. A total of 115 women (aged 63.6 ± 0.7 years; body mass index [BMI] 25.5 kg/m²; femoral neck [FN] T-score −1.8 ± 0.1) were randomly allocated to 8-month, twice-weekly, 40-minute HiRIT (5 sets of 5 repetitions, >80% to 85% 1 repetition maximum) or BB (low-intensity, Pilates-based training), stratified by medication intake, resulting in four groups: HiRIT (n = 42), BB (n = 44), HiRIT-med (n = 15), BB-med (n = 14). HiRIT improved LS BMD (1.9 ± 0.3% versus 0.1 ± 0.4%, p < 0.001) and stature (0.2 ± 0.1 cm versus −0.0 ± 0.1 cm, p = 0.004) more than BB. Both programs improved functional performance, but HiRIT effects were larger for leg and back muscle strength and the five times sit-to-stand test (p < 0.05). There was a positive relationship between maximum weight lifted and changes in LS BMD and muscle strength in the HiRIT groups. Exploratory analyses suggest antiresorptive medication may enhance exercise efficacy at the proximal femur and lumbar spine. Exercise compliance was good (82.4 ± 1.3%) and both programs were well tolerated (7 adverse events: HiRIT 4; BB 3). HiRIT improved indices of fracture risk significantly more than Buff Bones®. More trials combining bone medication and bone-targeted exercise are needed. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Variations in strength of vertebrae with age and their relation to osteoporosis

Fourth and fifth lumbar vertebrae were obtained at post mortem examinations of human subjects in the range 26 to 86 years and at the same time specimens were taken from the iliac crests for histological assessment of trabecular density (iliac crest score). After removal of pedicles and spinous processes the vertebrae were compressed in a testing machine to mechanical failure. The following values were obtained; breaking stress (load per unit area at failure), strain (percentage deformation) at failure and relative ash content (ash per unit volume). Strain at failure was independent of the size and strength of the vertebrae. The relative ash content and the iliac crest score were closely correlated. The relative ash content and the breaking stress both declined with increasing age, but the relation between them was not linear since the breaking stress fell more quickly than the ash content. Euler's equation for the buckling stress of a loaded column readily explains how in osteoporosis the reduction of the diameter of the vertical trabeculae and the loss of transverse ties cause loss of strength proportionately greater than the loss of osseous tissue. The results give no reason to suppose that in osteoporosis the quality of the osseous tissue is changed.

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Zusammenfassung Die vierten und fünften Lumbalwirbelknochen wurden von Obduktionen menschlicher Leichen innerhalb der Altersgrenzen von 26 und 86 Jahren gewonnen. Gleichzeitig wurden Proben von der Beckenschaufel entnommen, um Maßstäbe für die Bälkchendichte festzulegen (Beckenschaufelzahl). Nach Entfernung der Ansätze und Dornfortsätze wurden die Wirbelknochen in einer Prüfungsmaschine komprimiert, um mechanisches Versagen zu bestimmen. Folgende Werte wurden erhalten: Bruchbelastung (Gewicht pro Einheitsfläche bei Bruch), Beanspruchung (Prozentsatz von Deformation) bei Bruch und relativer Aschegehalt (Asche pro Einheitsvolumen). Die Beanspruchung bei Bruch war unabhängig von Größe und Stärke der Wirbelknochen. Zwischen dem relativen Aschegehalt und der Beckenschaufelzahl bestand eine enge Verbindung. Der relative Aschegehalt und die Bruchbelastung wurden mit fortschreitendem Alter kleiner, jedoch war die Beziehung zwischen diesen beiden Faktoren nicht linear, da die Bruchbelastung rascher als der Aschegehalt abnahm. MitEulers Gleichung für die Verbiegungsbelastung einer geladenen Säule läßt sich leicht erklären, auf welche Weise bei der Osteoporose die Reduktion des Durchmessers der Wirbeltrabekeln und der Verlust der transversen Verbindungen einen verhältnismäßig größeren Stärkeverlust hervorruft, als durch Verlust von Knochengewebe erklärt werden kann. Die Ergebnisse geben keinen Anlaß zu der Vermutung, daß bei der Osteoporose die Qualität des Knochengewebes eine Veränderung erfährt.

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Résumé Les quatrième et cinquième vertèbres lombaires sont prélevées post-mortem chez des sujets humains, âgés de 26 à 86 ans, et des échantillons de crête iliaque sont collectés simultanément pour établir histologiquement la densité des travées osseuses (index de la crête iliaque). Après avoir enlevé les pédicules et les apophyses épineuses, les vertèbres sont compressées dans une machine pour tester la résistance mécanique. Les valeurs suivantes sont déterminées: force de rupture (en poids par unité de surface au moment de la rupture), effort de rupture (en pourcentage de déformation) et contenu relatif en cendres (en cendres par unité de volume). L'effort de rupture est indépendant de la taille et de la force des vertèbres. Le contenu relatif en cendres et l'index de la crête iliaque sont en rapports étroits. Le contenu relatif en cendres et la force de rupture diminuent en fonction de l'âge, mais ce rapport n'est pas linéaire, car la force de rupture chute plus rapidement que le contenu en cendres. L'équation d'Euler pour une force courbe appliquée à une colonne chargée explique facilement comment, dans l'ostéoporose, la réduction de diamètre des travées verticales et la perte des attaches transversales sont responsables de la perte de force proportionellement plus élevée que la perte de tissu osseux. Les résultats ne permettent pas de supposer que, dans l'ostéoporose, la qualité du tissu osseux est altérée.

     

Traumatic fistula between internal iliac artery and external iliac vein

Traumatic iliac arteriovenous fistulas (AVFs) are extremely rare, with only two cases reported in literature involving the internal iliac artery and the external iliac vein. We report the case of a 23-year-old man who sustained a gunshot injury to the left lower quadrant of his abdomen and subsequently developed unilateral leg edema of "elephantiasic proportions." Intra-arterial digital subtraction angiography six years later was essential for diagnosis and comprehension of the pathomechanism. The angiographic examination showed an internal iliac false aneurysm, as well as a high-flow arteriovenous communication between the left internal iliac artery and external iliac vein complicated by thrombotic occlusion of the left common iliac vein. The initial vascular injury and the surgical management of simple ligation were thought to be responsible for the iliac AVF and the subsequent thrombosis of the common iliac vein. On the one hand, the thrombotic occlusion of proximal vein led to a sharp increase of mean pressure in the proximal and distal arteries and in the distal vein, resulting in chronic venous insufficiency with incompetent varicose veins. On the other hand, the restriction of venous outflow produced extreme peripheral edema and large superficial veins serving as collaterals to bypass the fistula. Vascular surgery could repair the lesion by closing and bypassing the AVF.