TGF-β and functional differentiation

A review of the pertinent literature suggests that TGF-1 may play a multifaceted role in functional differentiation of mammary epithelium. Evidence for the expression of TGF-1 RNA and the presence of functional TGF-1 protein in differentiating mammary epithelial cells from a pregnant mouse has been recently reported. The specific role of mammary-epithelial-cell-produced TGF-1 in the differentiating mammary gland is presently unclear. However, several possible functions are suggested from the following observations. Milk protein production is negatively regulated by exogenous TGF-1 during gestational development of the gland but not during lactation. Consistent with reports linking TGF-1 gene expression with mammary gland involution following lactation, overexpression of TGF-1 in the differentiating secretory epithelium leads to premature programmed cell death in the absence of a negative effect on secretory epithelial cell proliferation. A role for TGF-1 in cell cycle control and suppression of malignant progression independent from its inhibitory effect on epithelial cell growth has been demonstrated in keratinocytes. A similar function could provide protection against malignancy in proliferating mammary epithelium and account for TGF-1 suppression of mammary tumorigenesis in transgenic mice overexpressing transforming growth factor alpha (TGF-).³     

Traumatic lesion of the optic nerve

Summary This prospective study is based on 256 patients with severe brain injury. Six patients (2.3%) developed the clinical picture of inappropriate secretion of antidiuretic hormone (SIADH): 3 in the first 3 days following the injury, 3 after more than a week. Their ADH plasmatic level were measured by radio-immunoassay. In the former, many factors, largely iatrogenic, can explain the increased secretion of ADH we found and which is then definitely appropriate. It should be prevented by fluid restriction. In the latter, we found adequately low ADH levels, when the hypo-osmolarity is taken into account. Here, the aetiology seems to be a renal salt loss, eventually in relation to a natriuric factor (e.g. atrial natriuretic factor), justifying the term: Cerebral salt wasting syndrome. With the resistance to fluid restriction, the treatment still remains a problem.     

Maternal pregnancy vomiting and offspring salt taste sensitivity and blood pressure

The purpose of this study was to investigate the relationship between salt taste perception and blood pressure (BP) in normotensive adolescents as modified by maternal fluid losses during the first trimester of gestation. Seventy-two healthy adolescents (42 boys) aged between 9.0–21.1 years, recruited from the population-based RICARDIN study, were included. A maternal questionnaire about the duration of pregnancy, birth weight and vomiting or diarrhoea in the first trimester of gestation was collected. The sample was categorized into: vomiter descendents, those whose mother reported significant vomiting in the first trimester of gestation and non-vomiter descendents the remaining. Height, weight, and standardised BP measurement were recorded. Salt gustatory performance was assessed using a behavioral sensitivity test to determine the lower NaCl gustatory threshold, and a behavioral discrimination test, measuring the ability to distinguish among different saline solutions. Salt taste sensitivity showed a significant correlation with systolic BP (SBP) in vomiter descendents ( r =–0.66; P =0.003), but not in non-vomiter descendents. Adjusted by gender, and actual height and weight, salt sensitivity performance remained significantly related to SBP. An association between descendents SBP and maternal vomiting during gestation exists, adding a new element of evidence to the Barker hypothesis.     

Plasma osmolality,osmoregulation and prognosis after head injury

Summary 108 Patients with severe brain damage were examined for the course of plasma osmolality. In addition plasma values of Na⁺, K⁺, glucose and blood urea nitrogen (BUN) were measured simultaneously by auto-analyzer. The clinical status was registered daily by using a modified Glasgow coma scale. Outcome of the injured patients was registered by using the Glasgow outcome scale. 60 patients survived, 48 died, 39 of brain damage and 9 of secondary diseases, such as infection or embolism.Sustained severe brain damage is generally followed by disturbances of metabolic regulation. Quite often the osmotic regulation is disturbed. In most cases these disturbances are of hyperosmolar nature, their extent and duration being correlated to the prognosis.Hyposmolar deregulation occurs less frequently, and occasionally lead to peracute brain oedema (e.g. SIADH-syndrome). These dys-regulations are interpreted as disturbances of the central function of the diencephalon, in lethal cases even as hypothalamic death. Blood osmolality measurements should therefore be made early in states of acute cerebral disease to help establish a prognosis, control the treatment of water imbalance and to determine contra-indications to osmotherapy     

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.     

Renal adaptation to dietary amino acid alteration is expressed in immature renal brush border membranes

The transport of ions and solutes at the epithelial surface of the renal proximal tubule increases during periods of reduced dietary intake and decreases with dietary excess. We have used the sulfur-containing -amino acid, taurine, as a probe of this renal adaptive response to altered dietary sulfur amino acid intake to better understand the mechanisms of renal amino acid reabsorption. There exists an age-related precession of taurine uptake values by brush border membrane vesicles prepared from nursing rats from youngest to oldest. However, despite the immaturity of this transport mechanism, epithelial membranes become able to display a full renal adaptive response to altered sulfur amino acid intake sometime between the 7th and 14th day of life. This adaptive response is expressed in both up regulation and down regulation by means of a change in the initial rate of Na⁺-taurine cotransport. No changes in the lipid microenvironment of the membrane, as assessed by measurements of membrane fluidity, are evident. The lack of adaptation observed in 7-day-old pups may be due to immaturity of the Na⁺ transporting mechanism which energizes the uptake of amino acids.Supported in part by NIH grants AM 31682 and 37232     

Differentiation of intercalated cells in culture

The renal collecting duct is a heterogenous epithelium consisting of intercalated cells (ICCs) and principal cells (PCs). To test the hypothesis that the two cell types might originate from one another and to determine which one of the two is a stem cell, -ICCs and PCs were isolated by fluorescence-activated cell sorting and grown on permeable supports. Cultures of sorted PCs maintained their PC phenotype [electrogenic sodium (Na⁺) reabsorption and potassium (K⁺) secretion and expression of PC-specific antigens]. In contrast, cultures of sorted -ICCs acquired -ICC-specific functions (e.g. proton secretion) and gradually expressed functions specific for PCs (amiloride-blockable Na⁺ current and K⁺ secretion). Most cells in cultures of sorted -ICCs also acquired a central cilium, a characteristic feature of PCs. Dual-staining of -ICC cultures with cell-specific antibodies against surface antigens revealed that approximately 45% of the cells expressed only ICC-specific antigens and approximately 20% expressed only PC antigens. The remainder of the cells were ICC/PC hybrids and stained for both markers. Such hybrid cells were also observed in situ, albeit with a lower frequency, on kidney sections dualstained with cell type-specific markers. The proliferation rate of the two cell types, assessed by pulse labeling cells in S-phase with bromodeoxyuridine or staining with an antibody against a proliferation antigen (KI-67), revealed a significantly higher proliferation rate among -ICCs than PCs. In aggregate, these data suggest that -ICCs in culture are capable of differentiating into -ICCs and PCs and raise the possibility that -ICC is the stem cell of the collecting duct.     

Epigenetic changes accompanying human mammary epithelial cell immortalization

Acquisition of immortality may be an early and crucial step in malignant progression. We hypothesize that acquisition of unlimited growth potential in individual human mammary epithelial cells (HMEC) requires inactivation of several distinct negative growth constraints as well as reactivation of a mechanism to maintain telomeres on chromosomes. Some of the heritable changes that occur during HMEC immortalization, i.e., loss of expression of cyclin dependent kinase inhibitors p16^INK4a and p57^KIP2, loss of TGF-mediated growth inhibition, and derepression of telomerase, appear to occur without identifiable mutations in the genes and pathways involved. The absence of mutations, combined with the fact that the changes are often incremental over several cell generations even in clonal populations indicates that some changes associated with immortalization can be epigenetic. We have used the term conversion to describe the gradual epigenetic process in chemical carcinogen-immortalized HMEC that leads to activation of telomerase, stabilization of telomere length, and ability to grow uniformly well in the presence or absence of TGF. Characterization of the epigenetic mechanisms involved in immortalization may uncover additional factors that drive tumor progression, and that may be responsive to novel forms of intervention.     

Mechanism of action of β-glycerophosphate on bone cell mineralization

Summary Experiments were performed to determine whether -glycerophosphate (-GP) promoted mineralization in vitro by modulating bone cell metabolic activity and/or serving as a local source of inorganic phosphate ions (Pi). Using MC3T3-E1, ROS 17/2.8, and chick osteoblast-like cells in the presence of -GP or Pi, we examined mineral formation, lactate generation, alkaline phosphatase (AP) activity, and protein and phospholipid synthesis. Neither -GP nor Pi modulated any of the major biosynthetic activities of the bone cells. Thus, we found no change in the levels of phospholipids, and the total protein concentration remained constant. Measurement of lactate synthesis showed that -GP did not effect the rate of anaerobic glycolysis. Evaluation of medium Pi levels clearly indicated that -GP was hydrolyzed by bone cells; within 24 hours, almost 80% of 10 mM -GP was hydrolyzed. It is likely that this local increase in medium Pi concentration promoted rapid mineral deposition. Chemical, energy dispersive X-ray, and Fourier transform infrared analysis of the mineral formed in the presence of -GP showed that it was nonapatitic; moreover, mineral particles were also seen in the culture medium itself. Experiments performed with a cell-free system indicated that mineral particles formed spontaneously in the presence of AP and -GP and were deposited into a collagen matrix. We conclude that medium supplementation with -GP or Pi should not exceed 2 mM. If this value is exceeded, then there will be nonphysiological mineral deposition in the bone cell culture.     

Defects of TGF-β receptor signaling in mammary cell tumorigenesis

Transforming growth factor (TGF-)⁴ receptor expression and signal transduction in human breast cancer are reviewed as a function of estrogen receptor (ER) expression. ER⁺ breast cancer cells are generally resistant to the inhibitory effects of TGF-. The only known exception appears to be MCF-7 early passage cells which are initially sensitive to TGF-, but gain resistance after long-term passage in tissue culture. A number of studies have shown that loss of sensitivity is due to inadequate TGF- type II (TGFRII) receptor expression. Stable transfection of TGFRII into ER⁺ breast cancer cell lines results in the acquisition of TGF- sensitivity and reversion of malignancy. Although there are exceptions, ER^– breast cancer cells usually express TGFRII, but nevertheless show a low level of sensitivity to TGF-. Thus resistance in these cells implies a postreceptor mechanism. Given the frequency with which loss of TGF- sensitivity has been associated with loss of TGFRII, the ER^– breast cancer cell lines may represent valuable models for identifying postreceptor mechanisms of resistance.     

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)     

Multiple endocrine neoplasia type 1 in end-stage renal failure

A 59-year-old woman with chronic renal failure due to type 2 diabetes mellitus (DM) is presented. Her father and a brother had a history of brain tumor. Her blood urea nitrogen and serum creatinine levels were 102mg/dl and 4.5mg/dl, respectively. Her serum Ca²⁺ and Pi were within the normal range (9.4mg/dl and 5.4mg/dl, respectively). Her intact parathyroid hormone (PTH) level was 1730000pg/ml. A ^99mTc-methoxy-isobutylisonitrile scintigraphy showed high uptake in three parathyroid glands. A magnetic resonance image showed microadenoma in the pituitary gland. The serum gastrin level was high. Genetic examination revealed a mutation of the MEN1 gene (894–9 G A). From these findings, she was diagnosed with multiple endocrine neoplasia (MEN) type 1. Subsequently, a parathyroidectomy was performed successfully, a parathyroid gland was transplanted to her right forearm, and her serum Ca²⁺ level was controlled at 8.5–9.0mg/dl. It is very important to identify MEN1 if an end-stage renal disease (ESRD) patient has hyperparathyroidism with multigland involvement. Examination of the MEN1 gene may be valuable to make an accurate diagnosis and choose the appropriate therapy in some ESRD patients with hyperparathyroidism.     

Transforming growth factor-β and prostate cancer

Summary This review focuses on the possible role of transforming growth factor- isoforms 1–3 (TGF) in prostate cancer. TGF1 appears to inhibit the cellular proliferation of normal prostate cells. Surprisingly, TGF1 is overexpressed in prostate cancer. To help explain this apparent paradox, it has been revealed that with tumor progression, prostate cancer cells acquire reduced sensitivity to the growth-inhibitory effects of TGF1. Aberrations of the TGF1 signaling pathway at the prereceptor, receptor, or postreceptor level may lead to prostate cancer cell resistance to TGF1 growth inhibition. Indirectly, elevated levels of TGF1 may induce host effects that may be beneficial to prostate tumor growth by suppressing the immune system, promoting angiogenesis and extracellular matrix formation, and enhancing metastatic potential. Consequently, TGF1 appears to be important in prostate carcinogenesis and tumorigenicity. TGF2 and TGF3 are only briefly presented as very little is known about their role in prostate cancer.     

Linkage between O6-methylguanine-DNA methyltransferase (O6-MT) activity and cellular resistance to antitumour nitrosoureas in cultured rat brain tumour cell strains

Summary We have examined O⁶-methylguanine-DNA methyltransferase (O⁶-MT) activity of rat brain tumour cell strains with reference to cellular resistance to antitumour nitrosoureas, 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (nimustine, ACNU) and methyl-6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy--D-glucopyranoside (ramustine, MCNU). The values of O⁶-MT activity were 52 and 160 fmol/mg protein extract in 9 L and C 6 rat brain tumour cells, respectively; while HeLa S 3 cells, as a methyl excision repair positive (Mer⁺) cell strain, revealed a rather high value of 488 fmol/mg. 9 L cells indicative of a low O⁶-MT activity showed 13 M for ACNU and 18 M for MCNU at a 10% survival dose (SD₁₀), determined by a clonogenic cell assay as an index of cellular resistance. In contrast to this, C 6 cells revealed a SD₁₀ value of 67 M and 36 M for ACNU and MCNU, respectively, indicating higher resistance than 9 L cells. HeLa S 3 cells showed the highest SD₁₀ value as follows: 84 M for ACNU and 73 M for MCNU. The relationship between the O⁶-MT activity and the cellular resistance was almost linear, with relatively resistant cell lines exhibiting the higher levels of the O⁶-MT activity. This correlation between the O⁶-MT activity and the cellular resistance to nitrosoureas as ACNU and MCNU was not observed among other antitumour drugs, which included bleomycin (BUM), neocarzinostatin (NCS),cis-diamminedichloroplatinum (II) (CDDP), and etoposide (VP-16) in clinical use for brain tumour chemotherapy. This indicates that O⁶-MT activity can be an indicator of cellular resistance to antitumour nitrosoureas in the chemotherapy of brain tumours.     

Volume regulation of the brain tissue—a survey

Summary Though the brain bulk has been considered to be constant in several pressure homeostasis studies, the central nervous tissue may be responsible for the accommodation of extracerebral masses exceeding the volume regulation capacity of the cerebral blood and cerebrospinal fluid. Volume buffering of the nervous tissue may even be functioning in parallel, in conjunction with the fluid compartments. Of the existing volume regulatory models, the following are discussed:osmotic feedback (buffering) preventing major fluid shifts in osmotic or pressure disequilibrium at the blood brain barrier (BBB), and the4-compartment model, which under steady-state conditions can be regarded as an analogue of systemic tissue volume regulation, i.e. secretion of fluid at the BBB, bulk flow of interstitial space fluid (ISF) in the brain and absorption via the cerebrospinal fluid (CSF). The most recent data are presented, confirming that accommodation of space occupation by the nervous tissue is achieved via shrinkage of the extracerebral fluid (ECF), while the cell volume remains relatively constant. These findings confirm Hakim's classical hypothesis, based on biomechanical considerations, that the brain behaves like a sponge.The data presented in this survey point to a more general hypothesis: the brain interstitial space can vary in volume according to physiological and pathological stress, within certain bounds this being a reversible process which does not affect brain function.The potential role of the central neuro-endocrine system in brain volume regulation is discussed. Vasopressin (AVP) and atriopeptin (ANP) probably, function within the brain via a paracrine mechanism, as physiological regulators of brain cell and ISF volume. AVP and ANP are released in the central nervous system (CNS) independently from the periphery, and influence tissue water conservation and release directly. The future role of peptide analogues in the treatment of raised intracranial pressure and brain oedema are considered.Supported by Grants OTKA I/3 2728 and ETT T110/1990.     

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.     

Concomitant treatment of MBT-2 bladder tumour by tumour necrosis factor alpha and interferon alpha in conjunction with delayed type hypersensitivity immunotherapy

Summary In our previous study [9], we reported the anti-tumour effect of TNF on mouse bladder tumour (MBT-2) both in vivo and in vitro. Inoculation of a single dose of TNF alone caused significant but transient tumour growth inhibition. Subsequent repeated doses of TNF did not sustain or augment the antitumour effect. The current experiments were undertaken to assess the anti-tumour activity of (i)-concomitant treatment of TNF-A and IFN-A against MBT-2 bladder tumour and (ii)-concomitant TNF+IFN-A treatment in conjunction with T-DTH (delayed-type hypersensitivity) immunotherapy. Systemic administration of multiple doses of TNF+IFN-A in vivo caused initial partial tumour regression followed by tumour growth inhibition up to 14 days following treatment. This combined treatment showed an enhanced anti-tumour effect compared to TNF-A treatment alone. Immunotherapy of MBT-2 tumour-bearing mice with T-DTH immune effector cells alone did not cause significant tumour growth inhibition. In contrast, concomitant administration of both T-DTH effector cells and TNF+IFN-A in MBT-2 tumour-bearing mice resulted in significant tumour growth inhibition for up to 16 days. The immune effector cells conferring immunotherapy were isolated from the spleens of tumour-immunized, DTH-primed animals and were characterized as Lyt 1⁺2^- helper/DTH T cells (CD4⁺ phenotype). These cells mediate both DTH response to MBT-2 tumour antigens as well as anti-MBT-2 tumour protection. In vitro treatment of the immune cells with TNF-A resulted predominantly in the proliferation of Lyt 1⁺ T cells versus Lyt 2⁺ cells. The anti-tumour effect of TNF+IFN-A can be augmented by immunotherapy possibly via the immune capacity of tumour sensitized T-DTH effector cells.     

Expression of interferon-γ receptors on bladder cancer cells: does it correlate with biological response?

Summary Previously we have shown a differential biological response of three human bladder cancer cell lines (RT4, RT112 and MGH-U1) to gamma interferon (IFN-). The present study examines the relationship between the biological response and the expression of the interferon- receptor on the tumour cell surface. Using a competitive radioligand binding assay and Scatchard analysis, we measured the number and affinity of the IFN- receptors on each of the above cell lines. Individual cells from each line expressed large numbers (29,100–41,800) of high-affinity receptors (k _d =2.4–3.9×10¹⁰M). There was no statistically significant difference in either of these parameters between the three lines. We therfore conclude that the biological response of these bladder lines to IFN- does not relate to the number or affinity of its receptor on the plasma membrane of these tumour cells.     

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.     

Premature craniosynostosis a retrospective analysis of a series of 52 cases

Summary A retrospective analysis of a consecutive series of 52 cases with premature craniosynostosis is presented.Excellent functional, cosmetic, and social results could be achieved by resection of prematurely fused sutures and the creation of artificial growth sutures. Pronounced skull deformities have been corrected using the basket handle, the visor plasty, and the T-bone techniques or a combination of several of these skull form correction techniques. The surgical correction of the skull base by the frontal advancement technique in combination with orbitotomy was only necessary in 2 of our cases and could have been considered in 2 additional cases viewed retrospectively.Our results support the hypothesis that the primary cause of skull deformity is the premature closure of vault sutures and not a primary deformity of the skull base.