An interpretation of acute changes in plasma45Ca following parathyroid hormone administration to thyroparathyroidectomized rats

Acute changes in plasma calcium and⁴⁵Ca were studied in young adult male thyroparathyroidectomized (TPTX) rats injected with moderate doses of parathyroid hormone (PTH). For plasma calcium changes, comparison was made between rats fasted or fed prior to PTH injection. For plasma⁴⁵Ca changes, the effect of the time of administration of the radionuclide was also studied; this included rats injected with PTH 1 h after radionuclide (1 h⁴⁵Ca), 18 h later (18 h⁴⁵Ca) and more than 6 days later (6 day⁴⁵Ca). The results can be summarized as follows: (1) Plasma calcium changes were greater when PTH was injected into fed rather than into fasted rats. (2) PTH always produced a relative increase (compared to controls tested concurrently) in plasma⁴⁵Ca concentrations. This increase was the same in the 1 h⁴⁵Ca and the 18 h⁴⁵Ca groups. (3) Plasma⁴⁵Ca rose at least temporarily following PTH injection in the 18 h⁴⁵Ca group. (4) The⁴⁵Ca rise following PTH was always greater in fed than in fasted groups. (5) Plasma⁴⁵Ca specific activities (S.A.) tended to rise in the 6 day⁴⁵Ca group and to fall in the 18 h⁴⁵Ca group, following PTH injection. However, the⁴⁵Ca S.A. was always higher in fed than fasted groups. (6) In a few experiments in which³²P was injected with⁴⁵Ca, specific activity changes in plasma⁴⁵Ca following PTH injection werenot accompanied by similar changes in³²P specific activity.These results could not be adequately explained by PTH effects on bone resorption, but the data supported the postulate that PTH controls plasma calcium concentrations by increasing transport of calcium through the osteocyte-lining cell (osteoblast) bone cell complex from the bone fluid compartment to the ECF.     

Effects of Cilostazol on Human Venous Smooth Muscle

In this study, we evaluated the effect of therapeutic doses of cilostazol on human venous smooth muscle. Saphenous vein rings (two to four per patient sample) were suspended in tissue baths for isometric tension recordings. At the beginning of the experiment, optimal tension for isometric contraction was achieved for each ring in a stepwise fashion in the presence of norepinephrine (10^–2 M). Norepinepherine was then added cumulatively in half-molar increments and isometric tension developed by the rings was measured, thereby obtaining a dose-response curve. Following washout and reequilibration, the rings were precontracted with a 30-50% submaximal dose of norepinepherine determined from the dose-response curve and allowed to contract until a stable plateau was reached. Cilostazol was then added in a cumulative manner (680-2,720 g/L), and the tension generated was recorded. A total of 76 venous rings were tested, and all relaxed in the presence of cilostazol. The amount of relaxation increased as the concentration of cilostazol increased. Relaxation of 15±1.9% (mean±SEM) at low cilostazol doses (680 g/L) to 37±3% at high cilostazol doses (2,720 g/L) was demonstrated. A second finding of this study was demonstrated when the patient samples were divided according to the presence or absence of risk factors for arteriosclerosis. The specific risk factors examined included diabetes mellitus, smoking, hypercholesterolemia, and hypertension. The presence or absence of hypertension (n=52) or hypercholesterolemia (n=18) did not affect the amount of relaxation of the venous rings. Smokers (n=46) had less relaxation 16±2.4% (680 g/L) to 41±3.6% (2,720 g/L) compared to nonsmokers (n=53) who relaxed 22±3.5% (680 g/L) to 48±5.7% (2720 g/L). This did not reach statistical significance at any concentration cilostazol (p=0.11-0.18). Diabetics (n=53) did have statistically significantly less relaxation at every concentration of cilostazol compared to nondiabetics (n=11, p < 0.05). All venous rings relaxed in the presence of cilostazol. Veins of nondiabetics relaxed statistically significantly more than those of diabetics. Smokers had less relaxation than non-smokers, but this was not statistically significant. We are the first to demonstrate that human venous smooth muscle cells undergo relaxation when exposed to therapeutic concentrations of cilostazol.     

Effects of calcium and temperature on tension in isolated canine coronary artery

The effects of calcium and temperature on the tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the tension was significantly increased from 0mg with 0mEq·l ^–1 Ca to 33 ± 18mg with 0.2mEq·l ^–1 Ca at 37°C, from –40 ± 18mg with 0mEq·l ^–1 Ca to –17 ± 11mg with 0.2mEq·l ^–1 Ca at 30°C, from –77 ± 19mg with 0mEq·l ^–1 Ca to –52 ± 17mEq·l ^–1 with 1mEq·l ^–1 Ca at 25°C, from –88 ± 13mg with 0mEq·l ^–1 Ca to –41 ± 18mg with 2mEq·l ^–1 Ca at 20°C, from –125 ± 16mg with 0mEq·l ^–1 Ca to –116 ± 13mg with 2mEq·l ^–1 Ca at 15°C. Ca higher than 0.2mEq·l ^–1 produced a dose-dependent increase in tension between 37°C and 15°C. In spite of the presence of 4mEq·l ^–1 Ca, the development of tension was strongly supressed by lowering the temperature below 20°C, and completely inhibited at 10°C. The rate of a decrease in tension caused by cooling was about 5.5mg·°C^–1.This study demonstrated that Ca²⁺ produced a dose-dependent increase in tension in high-K solution, which was suppressed as the temperature was lowered.(Yoshida K, Fujii Y, Ina H, et al.: Effects of calcium and temperature on tension in isolated canine coronary artery. J Anesth 5: 172–176, 1991)     

A bone resorbing substance from bovine serum albumin (brA)

Summary A fraction (brA), which causes resorption of fetal rat bones in vitro, has been concentrated from bovine serum albumin by anion exchange column chromatography on DEAE Sephadex. This active fraction has also been prepared using DEAE Sephadex A-50 by a batch method with a 0.09M NaCl, 0.1M TRIS buffer, pH 8.35. BrA was 10–30 times more potent than the original albumin. The retained material, which constitutes the bulk of the protein and has less activity than the original albumin, elutes with 0.45M NaCl. Similar treatment of serum, or globulins does not yield brA. Further enhancement of the bone resorbing activity of brA can be obtained with (NH₄)₂SO₄ fractionation or extraction with CH₃OHCHCl₃. Heating at 55° C for 2 h or at 100° C for 10 min does not affect the activity; overnight incubation with protease destroys the bone resorbing effect. The bone resorbing activity is not removed by dialysis and does not correlate with the protease activity of the fraction. The action of brA is inhibited by 3 mM PO₄, 1 g/ml calcitonin or glucagon, 10^–7 M dexamethasone or 0.02 g/ml actinomycin D. The bone resorbing activity of brA is partially inhibited by 10^–7–10^–5 M indomethacin. PTH did not elicit bone resorption when added to cultures incubated in chemically defined medium supplemented with 0.1 mg/ml brA. However, brA did not inhibit PTH-induced resorption.     

Learning about combat stress from Homer'sIliad

Vietnam Veterans with severe post-traumatic stress disorder often report the following combat experiences: a leader's betrayal of what's right, lost responsiveness to claims outside a tiny circle of combat-proven comrades, grief and guilt for a dead special comrade, lust for revenge, renunciation of homecoming, feeling already dead, going berserk, dishonoring the enemy, and atrocities. These elements are all in Homer'sIliad account of Achilles, allowing the reader to witness them as they happen, so to speak. Homer's view of healing and regained humanity is discussed in relation to theIliad's final scene. TheIliad offers a cross-cultural look at men in battle, and raises questions about some assumptions in American military culture, particularly regarding grief and the need to degrade the enemy to make men fight. Betrayal of what's right and the berserk state are suggested as key pathogens for PTSD in combat soldiers.     

Bone mass in childhood is related to maternal diet in pregnancy

Evidence that birth weight is related to bone mass in later life suggests that the intrauterine environment programs the trajectory of subsequent bone development. To explore this hypothesis, we examined whether maternal diet in pregnancy, as assessed by the maternal food frequency questionnaire (FFQ) completed at 32 weeks gestation, is related to bone mass of the child, as measured by total body DXA carried out at age 9 years in the Avon Longitudinal Study of Parents and Children (ALSPAC). Diet records were linked to DXA scan results for the total body and spine sub-region and pooled between pre- and early pubertal boys and girls ( n =4,451). Regression analysis was carried out between DXA values and dietary factors following adjustment for social and other confounding factors. Maternal magnesium intake was related to total body BMC (=4.9, 7.4–23.1; g) and BMD (=4.9, 2.5–7.3; g/cm² ×10³) (standardized regression coefficient with 95% confidence limits; P <0.001). An equivalent relationship was no longer observed after adjusting for the height of the child, to which magnesium intake was also related (=0.48, 0.20–0.77; cm; P =0.001). Maternal intake of potassium was related to spinal BMC (=1.8, 0.8–2.9; g) and BMD (=10.5, 4.9–16.0; g/cm² ×10³) ( P =0.001), which was no longer observed after adjusting for the weight of the child, to which potassium intake was also related (=0.52, 0.16–0.88, P =0.005; kg). A significant association was also observed between maternal dietary folate intake and spinal BMC adjusted for bone area using a linear regression model (=0.55, 0.16–0.94; g; P =0.006), which persisted after adjusting for height and weight. Our observation that constituents of maternal diet are related to DXA measures at age 9 is consistent with the hypothesis that the trajectory of bone development in childhood is programmed by early life factors.This article was written by the authors and the ALSPAC study team.     

Plasma disappearance of rabbit α2 HS-glycoprotein and its uptake by bone tissue

Summary Plasma ₂HS-glycoprotein is specifically accumulated in calcified tissues. In the present studies this glycoprotein was isolated from plasma and after iodination with iodine-125 was injected intravenously into young rabbits. The tissue distribution and plasma disappearance rate of this radioactively labeled material were determined. Of the various tissues studied, bone showed the greatest retention of labeled glycoprotein expressed as percentage of the injected dose per gram tissue relative to the plasma content.The rate of loss of iodinated ₂HS-glycoprotein from plasma was similar to that of ₂HS-glycoprotein labeled endogenously by using¹⁴C-glucosamine or³H-glucosamine. The uptake of exogenously labeled³I- ₂HS-glycoprotein into bone tissue expressed as a percentage of the injected dose was similar to that of endogenously labeled¹⁴C- ₂HS-glycoprotein. These results suggest that the¹²⁵I-labeled material can be used to study further the metabolism of ₂HS-glycoprotein by bone tissue.     

Differential expression of transforming growth factor-β1 and β3 as well as C-FOS mRNA in normal human prostate,benign prostatic hyperplasia and prostatic cancer

Summary The discrepancy between the incidence of latent prostate cancer and that of clinically overt carcinoma suggests that there can be different courses in the biological progression of prostate cancer. As this cancer is detected increasingly at an infraclinical stage, markers are needed to indicate which lesions will progress and lead to the patient's death. To investigate the possibility that specific growth factors and/or proto-oncogenes are expressed differentially, we measured mRNA levels of transforming growth factors 1 (TGF-1), TGF-2 and TGF-3 and of the c-fos and c-jun oncogenes by Northern blotting in normal prostate, benign prostatic hyperplasia (BPH) and prostate cancer. Our data demonstrate that expression of TGF-1 increased, whereas that of TGF-3 fell to an almost undetectable level in carcinoma. Expression of c-fos followed the TGF-1 pattern, whereas no difference could be seen in c-jun expression in cancer as compared with BPH and normal prostate. The differential expression of TGF-1, TGF-3 and c-fos could possibly be used to improve the characterisation of prostate cancer. Long-term follow-up of patients may indicate whether mRNA levels of these growth factors and oncogenes correlate clinically and whether they can be used as markers for progression in human prostate cancer.     

Zur Bedeutung von β-hCG im serum als tumormarker fur das magenkarzinom

Zusammenfassung Einleitung: Nach neueren Untersuchungen ist davon auszugehen, daß bei des Hälfte von Patienten mit einem Magenkarzinom -hCG-positive Zellen im Tumor immunhistochemisch gefunden werden können. Ziel war daher, systematisch zu untersuchen, inwieweit -hCG-immunreaktive Magenkarzinome von einem Anstieg des Serum--hCG begleitet werden and dieses damit als Verlaufsparameter zur Verfügung steht. Methode: Bei 54 Patienten mit einem Magenkarzinom wurde zur immunhistochemischen Darstellung ein gegen -hCG gerichteter monoklonaler Antikörper (Fa. Sigma, 1:100) im APAAP-System verwendet. Die Auswertung wurde nach positiver and negatives Reaktion graduiert. Parallel wurde im Serum des Patienten -hCG präoperativ mit einem Enzymimmunoassay (MEIA, Fa. Abbot) bestimmt. Tumor-stadium, Grading and Tumor-lokalisation werden in die Auswertung mit einbezogen. Ergebnisse: Es wird bestätigt, daß 41% (22 von 54) des Karzinome, unabhängig von ihrer Lokalisation im Magen, eine positive immunhistochemische Reaktion gegen -hCG auslösen. Es zeigte sich in Abhängigkeit vom Tumorstadium eine positive -hCG-Immunreaktivität in 27% (6 von 22) des Tumoren ohne Lymphknoten- and Fernmetastasierung (T_1–4 N₀ M₀), in 54% (7 von 13) des Tumoren mit Lymphknotenaber ohne Fernmetastasen (T_1–4 N₁ M₀) und in 47% (9 von 35) des Tumoren mit Fernmetastasierung. Schlecht differenzierte Tumoren (G3–4) waren zu 42% (15 von 36) und gut differenzierte Tumoren (G_1–2) nur zu 39% (7 von 18) positiv. Aber lediglich bei einer Patientin war der -hCG-Spiegel im Serum erhöht. Zusammenfassung: Immunhistochemisch -hCG-positive Magenkarzinome werden vermehrt bei fortgeschrittenem Tumorstadium und Schlecht differenzierten Karzinomen gefunden. Diese Kar zinome scheinen aber nicht in ausreichender Menge -hCG ins Serum abzugeben, was zu serologisch meßbar erhöh-ten Werten führt. -hCG im Serum kann daher nicht als Prognosefaktor bzw. zur Verlaufskontrolle herangezogen werden. Abzuwarten bleibt, inwieweit die -hCG-Expression von Tumorzellen u. U. Einfluß auf die Propose der Patienten besitzt.

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Significance of -hCG in the serum as a tumour marker for gastric cancer

Introduction: Recent investigations indicate that in 50% of patients with gastric cancer, -hCG-posiitive cells can be found in the tumour by immunohistochemical investigations. The objective of this study was to investigate how often -hCG-immunoreactive gastric carcinomas were accompanied by an elevation in serum -hCG, that could have been used as a course control variable. Methods: In 54 patients with gastric carcinoma a monoclonal antibody directed against -hCG was used for immunohistochemical marking in the APAAP system. The evaluation was graded positive or negative. In parallel, serum -hCG was determined preoperatively using an enzyme immunoassay (MEIA). Tumour stage, grading and tumour locallization were determinants in the evaluation. Results: We found that 41% (22 of 54) of the carcinomas induced a :positive immunohistochemical response to -hCG, regardless of their location in the stomach. In relation to tumour stage, a positive -hCG immunoreactivity was apparent in 27% (6/22) of tumours without lymph node or distant metastases (TI -4N0M0), in 54% (7/13) of tumours with lymph node and without distant metastases (T1–4N1 M0) and in 47% (9/35) of tumours with distant metastases. Poorly differentiated tumours (G3–4) were positive in 42% (15/36) and well-differentiated tumors (G1–2) in 39% (7/18) of cases. In only 1 patient was the -hCG, level in serum elevated, however. Conclusions: -hCG-Positive gastric carcinomas are found more frequently in advanced tumour stages and poorly differentiated carcinomas. These carcinomas, however, seem not to excrete -hCG in sufficient amounts to produce measurable serum values. Therefore, -hCG cannot be used a prognostic factor or for course control. The relevance of -hCG expression of tumour cells to the patients' prognosis remains obscure.

     

Das periostale Wachstum,Hauptmittel zur funktionellen Anpassung des Schenkelhals-Schaft-Winkels (CCD-Winkel)

Zusammenfassung Nach konsequenter Untersuchung vieler Coxa valga-Fälle gemäß physikalischen und biologischen Gesetzen sowie morphologischen Standpunkten muß man als Hauptgestalter des Schenkelhals-Schaft-Winkels das periostale Wachstum betrachten und nicht, wie bis jetzt angenommen, das epiphysäre Längenwachstum.

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The increase in thickness of the bone as a basic means of functional adaptation of the femoral neck

Summary Consistent investigation and analysis of cases of Coxa valga, as well as careful consideration of biological and physical laws should lead to the conclusion that the formation of the CCD-angle is mainly due to the growth of the bone along its width growth caused by the periosteum rather than its elongation.

     

A comparative study of coagulation effects on the cortex of the rat using Nd-YAG (1.32 μm), Nd-YAG (1.06 μm) and CO2 lasers

This paper represents a comparative study on brain tissue of three lasers: Nd-YAG (1.32m); Nd-YAG (1.06 m); and CO₂ laser. The experimental studies were performed on rats. They consisted of a comparison between the thermal effects and the consequent histological lesions produced. The surface temperature of the cortex induced by each laser shot was measured with an infrared camera. The results show that there exists an excellent correlation between surface temperature and the histology of the lesions produced. It appears that for equivalent surface temperatures the cortical lesions 8 days after irradiation were similar for Nd-YAG (1.32m) and for CO₂ lasers but significantly different for the Nd-YAG (1.06m) laser. For example the depth of coagulation necrosis varied between 20 to 250m with the CO₂ laser using the power of 3 to 10 W at an exposure of 0.05 s with a fluence of 5J/cm² and varied from 210 to 260m using the Nd-YAG (1.32m) with the power of 5 to 14 W with an exposure of 0.4 s with a fluence of 50–170 J/cm². With the Nd-YAG (1.06m) the depth of coagulation necrosis varied from 490m to 550m using a power of 12 to 19 W with an exposure of 0.4 s with a fluence of 150–250 J/cm². It would appear that the Nd-YAG laser at a wavelength of 1.32m should be valuable in neurosurgery as this wavelength is highly absorbed by brain parenchyma and is transmissible with a fibre optic delivery system.

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Résumé Les auteurs presentent une étude comparative de la coagulation du parenchyme cérébral au moyen de différents lasers. Les études expérimentales ont été effectuées sur le cortex du rat. Elles ont consisté à comparer les effets thermiques et histologiques de 3 longueurs d'onde: Nd-YAG (1.32m), Nd-YAG (1.06m) et CO₂ (10.6m). La température corticale de surface induite par le tir laser a été mesurée au moyen d'une caméra infrarouge. Les courbes du profil thermique de chaque tir et de son évolution au cours du temps ont ainsi été obtenues. Les résultats montrent qu'il existe une excellente corrélation entre les données thermiques et les données histologiques recueillies pour chaque tir. Il apparaît ainsi que pour des augmentations de température équivalentes, les lésions corticales 8 jours après le tir sont similaires pour les lasers Nd-YAG (1.32m) et CO₂, mais significativement différentes pour le laser Nd-YAG (1.06m).Par exemple, le profondeur de nécrose varie entre 200 et 250m pour le laser CO₂ utilisé avec une puissance de 3 à 10 W, un temps d'exposition de 0.05 s et une fluence de 5 J/cm². La profondeur de nécrose varie entre 210m et 260m lorsqu'on utilise le laser Nd-YAG (1.32m) avec une puissance de 5 à 14 W, un temps d'exposition de 0.4 s et une fluence de 50 à 170 J/cm². Avec le laser Nd-YAG (1.06m), la profondeur de nécrose est beaucoup plus importante. Elle varie entre 490m et 550m pour une puissance comprise entre 12 et 19 W, un temps d'exposition de 0.4 s et une fluence de 150 à 250 J/cm².Ces résultats expérimentaux montrent que la longueur d'onde 1.32m est bien adaptée à la neurochirurgie puisqu'elle est bien asbsorbée par le parenchyme cérébral et qu'elle est transmissible par une fibre optique.

     

Effects of cyclosporins and transforming growth factor β1 on thyroid hormone action in cultured fetal rat limb bones

Summary To study the mechanism of action of thyroid hormones on bone, we examined the effects of immunosuppresive and nonimmunosuppressive cyclosporins, as well as of transforming growth factor ₁ (TGF₁), 17-estradiol (E₂), and dihydroxytestosterone (DHT) on thyroxine (T₄)-and triiodothyronine (T₃)-stimulated bone resorption in fetal rat limb bones. The immunosuppressive cyclosporins A (CsA) and G (CsG) inhibited thyroid hormone (T₄+T₃)-stimulated resorption and -glucuronidase release into the culture medium, whereas the weak or nonimmunosuppressive cyclosporins D (CsD) and H (CsH) did not show this effect. Increasing the medium calcium concentration reduced the ability of T₄ to stimulate ⁴⁵Ca release, while not significantly affecting the response to CsA. TGF₁ elicited a biphasic effect when administered together with T₄. During the first 3 days of culture, TGF₁ elicited a small, nonsignificant decrease in released ⁴⁵Ca; during a subsequent 3 days of culture, it enhanced T₄-stimulated bone resorption significantly. These effects differed from those of TGF₁ on parathormone-stimulated resorption. E₂ and DHT did not influence the action of T₄ on bone tissue. These results suggest that the mechanism of action of thyroid hormones on bone may involve immune factors, as well.     

β2-Microglobulin in postmenopausal osteoporosis

Summary The so-called bone-derived growth factor, or ₂-microglobulin, has a regulatory function in bone metabolism, stimulating osteoclastic activity. Osteoclastic activity is enhanced in postmenopausal osteoporosis, suggesting that ₂-microglobulin concentration may also be increased in this disease. ₂-microglobulin concentration was found to be raised (P < 0.001) in 30 women with postmenopausal osteoporosis as compared with 30 normal women of similar age; tartrate-resistant acid phosphatase concentration also was raised (P < 0.001), and total body bone mineral content was decreased (P < 0.001). Linear regression analysis revealed a highly negative correlation result between total body bone mineral content and ₂-microglobulin (r = 0.577,P < 0.001), and a positive correlation result between ₂-microglobulin and tartrate-resistant acid phosphatase concentration (r² = 0.806,P < 0.001). These findings, and the stimulatory effect of ₂-microglobulin on osteoclastic and osteoblastic activity, suggest that ₂-microglobulin may play an important role as a local regulatory factor in the pathogenesis of postmenopausal osteoporosis.     

Breathing pattern and respiratory mechanics in sevoflurane-anesthetized humans

In order to determine the respiratory effects of sevoflurane in humans, breathing pattern and mechanical behavior of respiratory system were investigated in ten subjects at anesthetic depth of 1MAC (minimum alveolar concentration). Average tidal volume and breathing frequency amounted to 275ml and 20.9 breaths per minute. Arterial carbon dioxide tension amounted to 45.6mmHg. Duration of inspiration was 1.06s and that of expiration was 1.92s. Mean inspiratory flow rate amounted to 259ml·s^–1. Average value of passive respiratory elastance determined by the method of Zin et al. amounted to 21.8cmH₂O·l ^–1, while those of active respiratory elastance and resistance obtained by the method of Behrakis et al. were 28.0cmH₂O·l ^–1 and 3.15cmH₂O·l ^–1·s^–1, respectively.Values of these variables were compared to those reported in halothane and enflurane anesthesia and possible explanations of the differences between the anesthetics are discussed.(Izumi Y, Kochi T, Isono S, et al.: Breathing pattern and respiratory mechanics in sevoflurane-anesthetized humans. J Anesth 4: 343–349, 1990)     

Potentiation of transforming growth factor (TGF-β1) by natural coral and fibrin in a rabbit cranioplasty model

The association of a biodegradable material and a growth factor could be of clinical value for treating bone defects. We therefore tested the association of transforming growth factor (TGF-1) in fibrin glue and coral granules to heal skull defects in rabbits. Adult rabbits underwent a double trepanation symmetrically in both parietal bones. Using histomorphometry, we compared bone repair after 1 month in control animals (n=5) and in animals treated with either TGF-1 as a single injection of 1 g in methylcellulose (n=5) or in fibrin glue (n=5), or with coral granules in fibrin glue (n=4) or with coral granules and TGF-1 1 g in fibrin glue (n=5). We measured the diameter of the remaining defect and the surface of the bone growth. TGF-1 without coral in either methyl cellulose or fibrin induced a partial closure of the defect as assessed by a significant decrease in the defect diameter, compared with the control group. However, the association of TGF-1 in fibrin and coral induced an area of the bone growth higher than in any other groups (P<0.05). Two months after surgery, this triple association induced a better healing of the defect than coral alone or control group. In each group treated with TGF-1, the mineralization rate was increased not only at the treated side but also in the contralateral defect which was untreated, suggesting a diffusion of the growth factor. Indeed, when pooled together, the diameter of the defect at the contralateral side of 14 animals that had received TGF-1 was reduced compared with the control group. Significant coral granules resorption occurred between month 1 and 2 and was unchanged by the addition of TGF-1. In conclusion, the triple association of coral granules and TGF-1 in fibrin could be of interest for treating bone defects.     

Changes of local brain tissue oxygen pressure after vasopressin during spontaneous circulation

Summary. Background. Brain tissue oxygen pressure (PbtO₂) correlates to cerebral blood flow (CBF) during spontaneous circulation, with one important regulator being nitric oxide (NO). Although it is established that arginine vasopressin (AVP) improves CBF and global cerebral oxygenation during cardiopulmonary resuscitation, it is unknown whether similar beneficial effects are present during spontaneous circulation. The purpose of this study was to investigate the effects of AVP with and without pre-treatment with the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on local brain tissue oxygenation in a beating heart model.Methods. Following approval of the Animal Investigational Committee, nine healthy piglets underwent general anaesthesia, and were instrumented with a probe in the cerebral cortex to measure PbtO₂. Each animal was assigned to receive AVP (0.4U·kg^–1), and after a wash-out period, L-NAME (25mg·kg^–1 over 20min) followed by AVP (0.4U·kg^–1). After each AVP administration, nitroglycerine (25µg·kg^–1 over 1min) as a NO donor was infused to test the vascular reactivity independently from NOS inhibition.Findings. Three minutes after administration of AVP, PbtO₂ increased significantly (P<.05; mean±SEM, 31±11 versus 43±14mmHg, +39%), compared with baseline. After pre-treatment with L-NAME, the changes of PbtO₂ after AVP were not significant (32±11 versus 28±10, –13%) when compared with the baseline.Conclusion. In this beating heart porcine model, local brain tissue oxygenation was improved after AVP alone, but not after inhibition of NO synthesis with L-NAME.     

Time-level relationship for nitric oxide and the protective effects of aminoguanidine in experimental spinal cord injury

Summary. Background. The secondary injury process following spinal cord trauma has been shown to involve different mechanisms such as excessive release of excitatory amino-acids, and induction of free radical induced lipid peroxidation. In this experimental study, the time-level relationship of the nitric oxide and the neuroprotective effects of aminoguanidine were investigated in a rat spinal cord trauma model.Methods. The experiments were performed on 63 Wistar albino rats divided into three groups; sham-operated control (Group 1), trauma created control (Group 2) and aminoguanidine group (Group 3). In groups 2 and 3, spinal cord trauma was produced at thoracic level by using weight the drop technique (at a severity of 50gr-cm). After the trauma, the rats in Group 3, received an intraperitoneal injection of 100mg/kg aminoquanidine twice a day for 3 days. The effects of the injury and the efficacy of aminoguanidine were determined based on biochemical parameters (lipid peroxidation and nitric oxide levels in tissue), and on light microscopy findings in cord tissue collected at different times post-injury. Biochemical parameters were performed one hour, three and five days after injury. Functional recovery was assessed at 3, and 5 days after cord trauma with the inclined-plane technique and Tarlovs motor grading scale.Findings. Although there was no statistically significant difference at the 1^st hour, the values of the tissue nitric oxide in trauma created controls were 42% higher on the 3^rd day and 40% higher on the 5^th day when compared with those in sham controls. The levels of the tissue lipid peroxidation in trauma created controls were 88% higher at the 1^st hour and 52.8% higher on the 5^th day when compared with shame controls, but there was no meaningful difference on the 3^rd day. In the trauma created control group, the mean motor function scores decreased to 1.16±0.40 and to 1±0 on the 3^rd and 5^th day, respectively. In this group the mean values of the inclined plane were 39.16±2.04 on the 3^rd day and 37.91±1.02 on the 5^th day. No statistically significant difference was observed in both tissue lipid peroxidation and nitric oxide levels for all time points between the aminoguanidine group and the sham-operated controls (p>0.01). The motor function scores were observed as 2.16±0.40 on the 3^rd day and as 3±0 on the 5^th day in aminoguanidine group. These values were significantly higher than the trauma created controls (p<0.01). Aminoguanidin treatment also improved the inclined plane performance of the rats; In this group, the mean values of the inclined plane scores were 44.58±2.92 and 52.91±1.88 on the 3^rd and 5^th days, respectively. These values were significantly higher than the trauma created controls (p<0.01).Interpretation. This study shows that the nitric oxide level does not increase in the spinal cord tissue during the first hour after the spinal cord trauma. It increases significantly in the spinal cord tissue not only three days but also five days following the trauma. Aminoguanidine treatment, which is started just after the trauma, can prevent both the nitric oxide production and lipid peroxidation in spinal cord tissue and it can improve the functional status of the animals. In this respect, aminoguanidine may have a potential role in the treatment of acute spinal cord injury.     

Inhaled Nitric Oxide Therapy After Fontan-Type Operations

Purpose Inhaled nitric oxide (NO) therapy is a newly developed strategy designed to reduce pulmonary vascular resistance after the Fontan-type operation. We reviewed our experience to evaluate its efficacy and true indications.Methods We retrospectively examined 47 children who received inhaled NO therapy after the Fontan-type operation between August 1996 and December 2002. The maximal dose of NO ranged from 5 to 30ppm (median 10ppm), and the duration of inhaled NO therapy ranged from 5h to 52 days (median 2 days).Results Inhaled NO significantly decreased the central venous pressure (CVP), from 16.2 ± 2.2 to 14.6 ± 2.2mmHg (P < 0.0001), and the transpulmonary pressure gradient between the CVP and left atrial pressure, from 9.9 ± 2.9 to 8.4 ± 2.7mmHg (P < 0.0001). It also increased the systolic systemic arterial pressure from 71.9 ± 15.2 to 76.8 ± 14.5mmHg (P < 0.05). In 26 patients with additional fenestration, inhaled NO led to a significant improvement in SaO₂ from 90.1% ± 9.6% to 93.3% ± 7.9% (P < 0.01). However, patients with a CVP <15mmHg or a transpulmonary pressure gradient <8mmHg, or both, after the Fontan-type operation, showed no significant changes in hemodynamics during inhaled NO therapy.Conclusions We propose that a CVP 15mmHg or a transpulmonary pressure gradient 8mmHg, or both, after Fontan-type operations are appropriate indications for inhaled NO therapy.     

Enamel matrix protein turnover during amelogenesis: Basic biochemical properties of short-lived sulfated enamel proteins

The formation and turnover of sulfated enamel proteins was investigated by SDS-PAGE, fluorography, and TCA-precipitations using freeze-dried incisors of rats injected intravenously with ³⁵S-sulfate (³⁵SO₄) and processed at various intervals from 1.6 minutes to 4 hours thereafter. Some rats were injected first with ³⁵SO₄ followed 5 minutes later by 0.3 mg of cycloheximide. This was done to terminate protein translation and allow events related to extracellular processing and degradation of the sulfated enamel proteins to be visualized more distinctly. Other rats were injected with cycloheximide followed at 0 minutes (simultaneous injection) to 30 minutes later by ³⁵SO₄. This was done to characterize the time required for proteins to travel from endoplasmic reticuium to Golgi apparatus, where they became sulfated. The results indicated that enamel organ cells (ameloblasts) rapidly incorporated ³⁵SO₄ into a major 65 kDa protein that was secreted into the enamel within 6–7.5 minutes. This parent protein appeared to be processed extracellularly within 15 minutes into major 49 kDa and 25 kDa fragments which themselves had apparent half-lives of about 1 and 2 hours, respectively. There were also many minor sulfated fragments varying in molecular weight (Mr) from 13–42 kDa, which appeared to originate from extracellular processing and/or degradation of the parent 65 kDa sulfated enamel protein or its major 49 kDa and 25 kDa fragments. Experiments with glycosidases further suggested that the majority of sulfate groups were attached to sugars N-linked by asparagine to the core of the 65 kDa sulfated enamel protein. The sulfated enamel proteins resemble acidic glycoproteins previously classified as enamelins. Unlike the enamelins, however, they are short-lived and do not appear to survive in enamel as it matures.     

Radiographic assessment of cementless hip prostheses: The “ARA” scoring system

Summary Charles Engh and Philippe Massin were the first to distinguish the radiographic patterns produced by the cementless type of hip arthroplasty vs those seen with the PMMA-cemented ones. These fundamental studies produced a new insight into the radiographic features of implants designed to be in direct contact with the host bone, and allowed a better understanding of cementless joint replacement technique. We planned to devise a easy-to-use and reliable system for the assessment of our radiographic data. This system was called ARA (AGORA Roentgenographic Assessment), firstly described in the SOFCOT monograph dedicated to HA-Coated Hip and Knee Replacement. In the analysis of hip arthroplasty radiographs, the questions to be answered could be: (1) Can we observe any changes as compared with the postoperative films? and (2) If so, are the changes normal, or are they to be considered as warning signs of threatening failure/evidence of established implant failure? Where there is no change in the surrounding bone, under conditions of normal physical activity, the implant/host bone system may be considered to be well adjusted, with adequate fixation and a good stress transfer pattern. Any signs that may subsequently appear could be either neutral, reflecting nothing more than an adaptive process, and not affecting the result of the arthroplasty; or adverse, in varying degrees. The step forward consists in setting up a scoring system: it is convenient to start from a total of 6 points, and to award negative points (from 1 to 4) for any of the adverse signs observed. The risk factors are then added up to produce a final score which shows how well the implant is doing in the host bone. Obviously, the score thus obtained will apply only to the time the radiographs were taken, and may change subsequently. The implant/bone system may be rated Excellent (ARA 5 or 6), Good (ARA 4), Fair (ARA 3), or Poor (ARA 2). A score of 5–6 suggests that there is every prospect of durable implant fixation; while a score of less than 2 is conclusive evidence of implant failure. The ARA Score constitutes a first attempt, and will need to be validated in large-scale use. We feel that this easy-to-use score may contribute reliable data that will permit a better understanding of the correlation between radiographic and clinical findings for all stems and cups (HA- and porous metal-coated devices).