Biomedical subjects

J R West

Publications and source records attributed to J R West.

At least 19 recordsLinked to original sources

PubMed2003

Measuring sediment exchange rates on an intertidal bank at Blacktoft, Humber Estuary, UK.

Results from a suite of Photo Electronic Erosion Pins (PEEPs) and manual pins installed on an intertidal bank at Blacktoft, near the confluence of the Rivers Trent and (Yorkshire) Ouse, UK are presented for summer 1997 (1 May-28 September). These reveal a pattern of erosion and deposition, which can be related to variations in tidal range, freshwater flow and wind speed over the period. During spring tides, greater resuspension of bed sediment leads to a greater availability of sediment in the water column for deposition on the bank. High wind speeds cause greater erosion of material from the bank due to wind-induced wave action. These processes of sediment exchange are also modified by the effects of biological activity on the sediment and of consolidation. It was demonstrated that the mean daily change in elevation of the upper part of the bank at Blacktoft was approximately 11 mm, which is two-three-fold less than the equivalent figure measured by a similar method at Burringham on the River Trent. It is thought that this difference is due to the effects of a greater concentration of suspended sediment settling onto the banks at Burringham, which are also subject to greater erosion due to their steeper slope. Results from a longer and more widespread survey of eight other intertidal banks in the Trent-Ouse Estuary system suggest that deposition and erosion occur in phase on all intertidal banks within the study area. Intertidal banks towards the upstream end of the system show much less variation in bank level than those further downstream.

Journal Article↗

PubMed2003

Steroid hormone concentration profiles in healthy intact and neutered dogs before and after cosyntropin administration.

The purpose of this study was to determine steroid hormone concentration profiles in healthy intact and neutered male and female dogs. Seventeen intact female dogs, 20 intact male dogs, 30 spayed female dogs, and 30 castrated male dogs were used in this study. Serum samples were collected before and 1h after cosyntropin administration, and serum concentrations were determined for cortisol, progesterone, 17-OH progesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, and estradiol. Intact male dogs had greater concentrations of DHEAS, androstenedione, and testosterone. Intact female dogs had greater concentrations of progesterone. There was no significant difference in estradiol concentration among the four groups. Intact male dogs had lower concentrations of cortisol post-stimulation. DHEAS and testosterone did not increase in response to ACTH in intact males, and estradiol concentrations did not increase in response to ACTH in any group. Results from this study will enhance interpretation of suspected adrenal and/or gonadal disorders of dogs. Because estradiol concentrations were similar in all groups of dogs, measuring estradiol may not be a useful diagnostic test. Cortisol concentrations for intact male dogs with hyperadrenocorticism may be lower than those of female or neutered dogs.

17-alpha-Hydroxyprogesterone↗

PubMed2002

The decay of chlorine associated with the pipe wall in water distribution systems.

Free chlorine decay rates in water distribution systems for bulk and wall demands should be modelled separately as they have different functional dependencies. Few good quality determinations of in situ wall demand have been made due to the difficulty of monitoring live systems and due to their complexity. Wall demands have been calculated from field measurements at 11 locations in a distribution system fed from a single source. A methodology for the laboratory determination has been evolved and shown to give results that are similar to the in situ results. Pipe materials were classified as either having high reactivity (unlined iron mains) or low reactivity (PVC, MDPE and cement-lined ductile iron). The results indicate that wall decay rates for the former are limited by chlorine transport and for the latter by pipe material characteristics. The wall decay rate is inversely related to initial chlorine concentration for low reactivity pipes. In general, water velocity increases wall decay rates though the statistical confidence is low for low reactivity pipes. A moderate biofilm coating did not influence the wall decay rate for low reactivity pipes.

Biofilms↗

PubMed2002

Durability and strength of Steinmann pin augmentation in cemented tibial defects.

It has been argued that Steinmann pin augmentation does not improve the biomechanics of polymethylmethacrylate reconstruction for massive defects of bone. The current authors investigated whether pin augmentation of polymethylmethacrylate in the reconstruction of noncontained defects of bone improved the biomechanical properties of the reconstruction as compared with polymethylmethacrylate alone when minimal or large bone porosity is present. Large noncontained defects were created in 10 pairs of human tibias. In Group 1, five left tibias had reconstruction with polymethylmethacrylate augmented with three, 5-mm diameter by 10-mm deep holes into lateral condyle cancellous bone. Right tibias had identical reconstruction with three, 3/16-inch threaded pins placed into the medullary canal. In Group 2, three, 10-mm diameter by 10-mm deep holes were created in both pairs. The left tibia had polymethylmethacrylate reconstruction and the right tibia had polymethylmethacrylate and pin augmentation. Specimens were subjected to 2000 compressive cycles then loaded to failure. In Group 1, cycles and load to failure were significantly lower in reconstructions without pins compared with reconstructions with pins. No significant difference was observed between reconstruction techniques in Group 2. In reconstructions without pins, large diameter holes had significantly better cyclical durability. Pins improved survival compared with no pins.

Adult↗

PubMed2001

Early postnatal ethanol intubation blunts GABA(A) receptor up-regulation and modifies 3alpha-hydroxy-5alpha-pregnan-20-one sensitivity in rat MS/DB neurons.

Previously we found postnatal binge-like ethanol exposure using an artificial-rearing method in the rat delayed developmental up-regulation of GABA(A) receptors (GABA(A)Rs) in both medial septum/diagonal band (MS/DB) and cerebellar Purkinje neurons. In the present study, the impact of ethanol on developing GABA(A)Rs in MS/DB neurons was further tested under conditions not requiring anesthesia or maternal deprivation. Nursing rat pups received ethanol (4.5-5.25 g/kg/day) on postnatal days (PD) 4-9, which was administrated manually by oral intragastric intubation. This treatment caused dose-dependent blunting of peak GABA(A) receptor whole cell currents in acutely dissociated MS/DB cells on PD 12-15. The threshold with oral intubation was slightly higher than previously observed for artificial-rearing (4.9 vs. 4.5 g/kg/day). The previously observed reduced sensitivity of GABA(A)Rs to Zn(2+)-inhibition after ethanol was not found with the intubation model. In studies only carried out using the intubation method, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha-OH-DHP) caused an allosteric concentration-dependent potentiation of currents activated by non-saturated concentrations of GABA. A bicuculline sensitive direct activation of GABA(A)Rs also occurred with higher concentrations of 3alpha-OH-DHP alone. Ethanol intubation up-regulated allosteric neurosteroid potentiation with low concentrations of GABA, but did not change direct agonist actions of 3alpha-OH-DHP. Finally, 3alpha-OH-DHP did not prime ethanol insensitive GABA(A)Rs to become sensitivity to acute ethanol potentiation. These results indicate ethanol consistently blunts postnatal GABA(A) receptor up-regulation across early postnatal binge-type ethanol exposure models and may increase positive modulation of GABA(A) receptors by endogenous neurosteroids.

Age Factors↗

PubMed2001

The potential for biofilm growth in water distribution systems.

Biofilms on pipe walls in water distribution systems are composed of bacteria in a polymeric matrix, which can lead to chlorine demand, coliform growth, pipe corrosion and water taste and odour problems. The majority of previous studies have been laboratory or pilot plant based and few results are available for field conditions. In this study, field observations of biofilm were made using biofilm potential monitors. The monitor results were compared with pipe samples taken from the distribution system and with laboratory pipe reactors. An empirical equation quantified the inhibitory effects of free chlorine and decrease of temperature on biofilm growth. With water having total organic carbon concentrations in the range 1.5-3.9mg/1 a free chlorine residual of 0.2 mg/l was needed to reduce biofilm concentration to below 50 pg ATP cm2. Pipe material influenced biofilm activity far less than chlorine with mean biofilm activity being ranked in the order glass (136 pg ATP/cm2) < cement (212 pg ATP/cm2) < MDPE (302 pg ATP/ cm2) < PVC (509 pg ATP/cm2).

Biofilms↗

PubMed2001

Regional differences in cell loss associated with binge-like alcohol exposure during the first two trimesters equivalent in the rat.

Women who abuse alcohol during pregnancy may deliver offspring who could be diagnosed with fetal alcohol syndrome (FAS) or a less severe deficit involving cognitive and behavioral disorders. The severity of the deficits may involve the interaction of several known risk factors, such as alcohol consumption pattern or duration, the timing of alcohol consumption relative to critical windows of vulnerability, or the inherent differential vulnerability among the various brain regions to alcohol-induced brain injury. In this study, we explore the vulnerability of the different brain regions by making cell counts from multiple brain regions. Specifically, we used stereological cell-counting techniques to estimate the total cell numbers in the cerebellum (Purkinje and granule cells), olfactory bulb (mitral and granule cells), hippocampus (CA1 and CA3 cells), and dentate gyrus (granule cells). Groups of timed-pregnant Sprague-Dawley rats were assigned to one of five treatments: alcohol by intragastric intubation (2.25, 4.5, or 6.5 g/kg/day), nutritional control [pairfed and intubated=Pairfed) and intubated], and normal control (Chow). Treatments began on embryonic day 1 (E1) and continued through E20. On E33 (usually postnatal day 10), all offspring were perfused intracardially with saline followed by fixatives. Representative forebrains, cerebella, and olfactory bulb from each group were processed for cell counting. The optical dissector was used to obtain cell densities, while Cavalieri's principle was used to calculate the reference volume. The product of density and volume gave unbiased estimates of the total neuronal number within each brain region. Overall peak BACs (regardless of sampling day) for the three alcohol groups averaged 136, 290, and 422 mg/dl for the 2.25-, 4.5-, and 6.5-g/kg groups, respectively. The total number of cerebellar Purkinje cells was reduced in the 6.5-g/kg group relative to controls, while the total number of olfactory bulb mitral cells and hippocampal CA1 and CA3 pyramidal cells from all alcohol-treated groups was not different from controls. Total numbers of granule neurons were reduced in the cerebellum and olfactory bulb of offspring exposed to 4.5 or 6.5 g/kg/day, but granule cell numbers in the dentate gyrus were not affected by the prenatal alcohol treatment. Taken together with previous findings, these data demonstrate that prenatal alcohol exposure results in regional vulnerability of various brain structures and underscores the variability of deleterious effects of alcohol on brain development.

Animals↗

PubMed2001

Third trimester binge ethanol exposure results in fetal hypercapnea and acidemia but not hypoxemia in pregnant sheep.

BACKGROUND: The mechanisms by which maternal ethanol abuse during pregnancy causes neurodevelopmental injury in the fetus are not well understood. The purpose of this study was to use a chronically instrumented fetal sheep model system to determine if a binge pattern of ethanol exposure administered throughout the third trimester reduced fetal arterial partial pressure of oxygen (PaO2); a positive finding would support the hypothesis that fetal hypoxemia may play a role in mediating ethanol-related birth defects. METHODS: Pregnant ewes received saline or 0.75, 1.25, 1.5, or 1.75 g/kg of ethanol intravenously over 1 hr beginning on day 109 of gestation (term = 145 days) for 3 consecutive days per week followed by 4 days without exposure. The fetuses were surgically instrumented on day 113, and experiments were performed on days 118 or 132, the 6th and the 12th ethanol exposure, respectively. RESULTS: Ethanol infusions resulted in peak blood ethanol concentrations of 80.8 +/- 6.5, 182.5 +/- 13.5, 224.4 +/- 13.9, and 260.6 +/- 20.0 mg/dl +/- SEM (maternal) and 70.0 +/- 5.9, 149.7 +/- 9.0, 216.9 +/- 14.0, and 233.3 +/- 19.8 mg/dl +/- SEM (fetal) in response to the 0.75, 1.25, 1.5, and 1.75 g/kg doses, respectively. Maternal and fetal heart rate and maternal blood pressure increased whereas fetal blood pressure decreased in a dose-dependent manner in response to ethanol infusions. Maternal and fetal arterial pH decreased and arterial partial pressures of carbon dioxide increased in response to ethanol infusions. Maternal PaO2 decreased whereas fetal PaO2 did not change in response to ethanol infusions. CONCLUSIONS: A binge ethanol exposure paradigm, three consecutive days per week throughout the third trimester at ethanol doses that created blood ethanol concentrations commonly achieved by human ethanol abusers, resulted in changes in maternal and fetal heart rate, changes in blood pressure, hypercapnea, acidemia, and maternal, but not fetal, hypoxemia. We conclude that in an ovine model system, ethanol doses that create blood ethanol concentrations as high as 260 mg/dl do not result in fetal hypoxemia. Remaining issues to address with this model system are whether neurodevelopmental injuries that are associated with maternal ethanol abuse are mediated by a reduction in fetal cerebral blood flow, fetal hypercapnea, or acidemia.

Abnormalities, Drug-Induced↗

PubMed2001

Zinc supplementation does not attenuate alcohol-induced cerebellar Purkinje cell loss during the brain growth spurt period.

BACKGROUND: Alcohol-induced zinc deficiency is one of the mechanisms proposed as a cause of developmental brain damage associated with fetal alcohol syndrome. It is known that alcohol exposure during the brain growth spurt period leads to cerebellar Purkinje cell loss. Therefore, this study examined whether zinc supplementation was capable of preventing alcohol-induced Purkinje cell loss in the cerebellar vermis in a neonatal rat model system. METHODS: Sprague-Dawley rat pups were given alcohol (EtOH; 4.5 g/kg/day), zinc (Zn; 0.54 mg/ml diet; [10 times the regular diet Zn concentration]), or both from postnatal days (PD) 4 through 9 using the artificial-rearing paradigm. A gastrostomy control (GC) and a suckle control group (SC) also were included. All pups were killed on PD 10. Following perfusion, the cerebellar vermis was dissected and processed for stereological cell counting. The total number of Purkinje cells and the volume of the cerebellar vermis were determined. RESULTS: Alcohol produced a significant loss of Purkinje cells compared with that in the GC group (no EtOH and no Zn supplement). The zinc supplementation had no effect in attenuating alcohol-induced Purkinje cell loss in the cerebellar vermis. In fact, the serum zinc concentration data indicated higher zinc concentrations following either EtOH or Zn treatment. Interestingly, the GC group showed a significantly lower zinc concentration compared with the SC group, even though no significant difference in Purkinje cell numbers was observed between these two control groups. CONCLUSION: These findings indicate that alcohol exposure during the third trimester equivalent did not result in zinc deficiency in this neonatal rat model system, nor did zinc supplementation rescue the alcohol-induced Purkinje cell loss in the cerebellar vermis. These findings showed clearly that the serum zinc concentration was not correlated with Purkinje cell loss, suggesting that alcohol-induced loss of cerebellar Purkinje cells in this neonatal rat model system is independent of the availability of serum zinc.

Animals↗

PubMed2001

Fetal alcohol exposure and temporal vulnerability: effects of binge-like alcohol exposure on the ventrolateral nucleus of the thalamus.

BACKGROUND: Prenatal alcohol exposure disrupts motor performance in affected offspring. The ventrolateral nucleus (VLN) of the thalamus functions to relay information between the cerebellum and motor cortex. Reductions in the size of the thalamus have been found in children with fetal alcohol syndrome, and therefore a rat model system was used to determine whether VLN size and neuronal number were altered by alcohol exposure during development. METHODS: Rat pups were exposed to alcohol in utero during the first 10 days of gestation (first trimester equivalent), the second 10 days of gestation (second trimester equivalent), or the first two trimesters equivalent combined. Some pups were exposed to alcohol in utero during the time of VLN neurogenesis. In addition, offspring from some of the dams treated during the first two trimesters equivalent were reared artificially from postnatal day (P) 4 through P9 (part of the third trimester equivalent) and received binge-like alcohol during this time, resulting in offspring exposed to alcohol during all three trimesters equivalent. Other offspring from untreated dams were reared in the same manner but received alcohol only during the third trimester equivalent. Control animals (nutritional and untreated) were reared for all treatment conditions. All pups were perfused on P10. RESULTS: A unique effect of alcohol treatment was not found for the VLN volume or the number of neural cells within the VLN. However, the period of VLN neurogenesis was found to be sensitive to both alcohol and nutritional control treatments, resulting in significant decreases in the VLN volume and neural cell number. CONCLUSIONS: Motor deficits seen in offspring exposed prenatally to alcohol do not seem to result from direct effects on the structure of the VLN of the thalamus.

Animals↗

PubMed2001

Alcohol-mediated Purkinje cell loss in the absence of hypoxemia during the third trimester in an ovine model system.

BACKGROUND: Although the mechanisms that underlie fetal alcohol-induced neuronal loss have not been determined, hypoxia/hypoxemia has been considered a leading candidate. This study was designed to test the hypothesis that neuronal loss could occur in the developing brain in the absence of fetal hypoxemia. METHODS: Three groups of pregnant sheep were used: a control group, a binge-drinking group, and a pair-fed group. The alcohol and pair-fed animals were anesthetized on day 113 of pregnancy, and the mothers and fetuses were instrumented with arterial and venous catheters. All animals were killed on day 133. Stereological cell counting techniques were used to estimate the total number of Purkinje cells in the fetal cerebellum. RESULTS: Peak maternal and fetal blood alcohol concentrations did not produce fetal hypoxemia. Nevertheless, there was a 25% loss of Purkinje cells of the cerebellum in the alcohol-exposed fetuses compared with that in the pair-fed controls. The loss of neurons was not accompanied by microencephaly or a concomitant decrease in either cerebellar weight or volume of the fetal cerebellum. CONCLUSIONS: Neuronal loss can be observed after alcohol exposure during the third trimester equivalent in fetal sheep in the absence of alcohol-induced hypoxemia. Furthermore, cell loss in the absence of deficits in gross brain weight or regional brain volume indicates that the lack of gross brain volume deficits from magnetic resonance imaging techniques is not a reliable indication that the brain is unaffected by the alcohol exposure.

Algorithms↗

PubMed2001

Fetal and maternal sheep hypothalamus pituitary adrenal axis responses to chronic binge ethanol exposure during the third trimester equivalent.

BACKGROUND: We tested the hypothesis that in utero ethanol exposure results in changes in fetal and maternal adrenocorticotropin (ACTH) and cortisol during the third trimester equivalent, by using a chronically instrumented fetal sheep model. METHODS: Pregnant ewes received saline or ethanol intravenously 3 consecutive days per week from day 109 to day 132 of gestation. Fetal and maternal blood samples were collected on days 118 and 132. RESULTS: Maternal and fetal ACTH and cortisol values increased on days 118 and 132 of gestation in response to ethanol infusions that created blood ethanol concentrations (BECs) that are easily achievable by human drinkers. Peak ACTH and cortisol values were detected 30 to 60 min after peak BECs were achieved. CONCLUSIONS: Chronic ethanol exposure during the third trimester equivalent in sheep resulted in repeated activation of the hypothalamus-pituitary-adrenal axis in both the mother and fetus. Temporally, the patterns of maternal and fetal responses to ethanol infusion were similar. We conclude that ovine maternal ethanol exposure during the third trimester equivalent increases fetal ACTH and cortisol concentrations, hormonal responses that may play a role in mediating alcohol-related birth defects.

Adrenocorticotropic Hormone↗

PubMed2001

Nicotine decreases blood alcohol concentration in neonatal rats.

BACKGROUND: Our previous findings suggested that the intragastric coadministration of alcohol and nicotine to neonatal rats resulted in a significant decrease from the predicted peak blood alcohol concentration (BAC). We hypothesized that the coadministration of alcohol and nicotine would produce a nicotine dose-related decrease in peak BAC and a change in the BAC time curve profile. METHODS: Sprague-Dawley rat pups were given alcohol and nicotine simultaneously via intragastric infusion. Two sets of nicotine doses were used in two independent studies. The low doses of nicotine were examined after the study of high doses of nicotine administration because of the possible ceiling effects from these nicotine doses on lowering BACs. RESULTS: The results not only confirmed that the peak BAC was lowered by nicotine, but also generated new findings showing that the profile of BAC time curve was affected by these doses of nicotine. Concerns about possible ceiling effects led us to conduct another experiment to examine the effects of lower doses of nicotine on BACs. Those results showed a significant decline in BACs after cotreatment with 0.5 or 1 mg/kg nicotine and less robust changes on the BAC curve profiles. Although the nicotine dose at 0.25 mg/kg/day did not affect significantly the overall BAC profile, it did lower the peak BAC. CONCLUSIONS: Nicotine is capable of lowering the peak BAC among neonatal rat pups. Furthermore, the pattern of the BAC time curve seems to be more affected by high doses of nicotine.

Animals↗

PubMed2001

Developmental alcohol and circadian clock function.

Studies in rats found that alcohol exposure during the early postnatal period, particularly during the brain-growth-spurt period, can result in cell loss in various brain regions and persistent behavioral impairments. Some investigators have speculated that the body's internal clock, which is located in the suprachiasmatic nuclei (SCN) in the brain, may also be affected by developmental alcohol exposure. For example, alcohol-induced damage to the SCN cells and their function could result in disturbances of the circadian timekeeping function, and these disturbances might contribute to the behavioral impairments and affective disorders observed in people prenatally exposed to alcohol. Preliminary findings of studies conducted in rats suggest that developmental alcohol exposure may indeed interfere with circadian clock function as evidenced by a shortened circadian sleep-wake cycle and changes in the release of certain brain chemicals (i.e., neuropeptides) by SCN cells.

Animals↗

PubMed2001

Drinking patterns and alcohol-related birth defects.

The consequences of maternal alcohol use during pregnancy on the outcome of offspring depend, among other factors, on the amount and pattern of alcohol consumption. Animal studies found that bingelike drinking patterns, in which the fetus is exposed to high blood alcohol concentrations (BACs) over relatively short periods of time, are particularly harmful, even if the overall alcohol amount consumed is less than those of more continuous drinking patterns. Long-term studies in humans have confirmed that children of binge-drinking mothers exhibited especially severe cognitive and behavioral deficits. Binge drinking may be particularly harmful because it results in high BACs, may occur during critical periods of brain development, and may be associated with repeated withdrawal episodes.

Abnormalities, Drug-Induced↗

PubMed2000

Glial-derived neurotrophic factor (GDNF) prevents ethanol-induced apoptosis and JUN kinase phosphorylation.

Ethanol exposure during neural development leads to substantial neuronal loss in multiple brain regions. Our previous research indicated that exogenous glial-derived neurotrophic factor (GDNF) attenuated ethanol-induced cerebellar Purkinje cell loss. Additionally, ethanol decreased GDNF release suggesting that ethanol disrupts GDNF-signaling pathways. The present experiments utilized a homogeneous GDNF-responsive neuroblastoma cell line (SK-N-SH) to test the hypothesis that exogenous GDNF could attenuate ethanol-induced cell loss by suppressing cytotoxic signaling pathways and cell suicide. We measured two independently regulated markers of apoptosis, DNA fragmentation and the externalization of phosphatidylserine to the outer cell membrane leaflet. Ethanol induced a dose-related increase in both apoptosis and necrosis. Lower concentrations of ethanol (34 and 68 mM) specifically increased DNA fragmentation, while all concentrations (up to 137 mM) increased phosphatidylserine translocation, suggesting that ethanol induction of apoptosis is not a unitary process. Furthermore, only higher concentrations of ethanol (103 and 137 mM) induced necrosis. Additionally, ethanol specifically induced phosphorylation of c-jun N-terminal-kinase (JNK), a mitogen-activated protein (MAP) kinase selectively associated with apoptosis. In contrast, ethanol did not alter the phosphorylation of another MAP kinase, the extracellular signal-regulated kinases (ERK) that mediate cell survival. Thus, ethanol activated specific intracellular cell death-associated pathways and induced cell death. GDNF, in turn, prevented both ethanol-induced apoptosis and the activation of the death-associated JNK cascade. Therefore, GDNF may regulate multiple pathways to prevent ethanol-induced cell loss.

Annexin A5↗

PubMed2000

Calcaneocuboid joint pressure after lateral column lengthening in a cadaveric planovalgus deformity model.

The purpose of this study is twofold: first, to measure the joint contact pressure across the calcaneocuboid joint in a planovalgus deformity and compare the results to pressures measured in a normal foot; and second, to determine the change in pressure across the calcaneocuboid joint after an Evan's-type calcaneal lengthening osteotomy. The effect of this procedure on the calcaneocuboid joint was evaluated using seven cadaver feet to measure peak pressure across the calcaneocuboid joint under a constant load. Each foot was sectioned medially to reproduce a deformity consistent with an adult, acquired flatfoot. Each flatfoot deformity was then corrected using a ten-millimeter lateral column lengthening osteotomy. Joint pressures were measured in the normal foot, the created flatfoot and then in the corrected flatfoot. Peak pressures across the joint increased significantly from baseline in the flatfoot (p <0.05). However, the change in pressure from the flatfoot to the corrected foot was not significant, and in some cases peak pressures in the corrected foot were actually lower than in the flatfoot. These findings indicate that calcaneal lengthening through an Evan's osteotomy does not increase pressure across the calcaneocuboid joint beyond physiologic loads in the flatfoot.

Arthritis↗

PubMed2000

Ethanol induces Fas/Apo [apoptosis]-1 mRNA and cell suicide in the developing cerebral cortex.

INTRODUCTION: Animal studies modeling fetal alcohol syndrome have demonstrated that developmental exposure to alcohol is associated with decreased brain weight and significant neuronal loss in multiple regions of the developing brain. Our previous data suggest that the Fas/Apo [apoptosis]-1 receptor is transiently expressed in the developing cerebral cortex during the peak period of naturally occurring apoptotic cell death and maximum sensitivity to alcohol. Therefore, we hypothesized that ethanol increases the expression of suicide receptors such as Fas/Apo-1 in the developing fetal cerebral cortex and leads to an upregulation or extension of the normal period of apoptosis and consequent disorganization of the neural circuitry. METHODS: Ethanol was administered in one of four doses (120, 320, 630, and 950 mg/dl) to organotypic explant cultures of the developing cerebral cortex established from postnatal day 2 rats and maintained for 6 days in vitro. The number of cells expressing Fas/Apo-1 receptor mRNA was counted. Apoptosis was measured by the use of two independent assays; a cell death enzyme-linked immunosorbent assay for DNA fragmentation and flow cytometric analysis of Annexin-V binding to phosphatidylserine externalized to the outer leaflet of the plasma membrane. Necrosis was also estimated by two independent measures, the amount of lactate dehydrogenase released into culture medium and flow cytometric analysis of cells that were positive for both Annexin-V and propidium iodide. RESULTS: A significantly larger number of developing cortical cells expressed Fas/Apo-1 mRNA at the lower doses (120 and 320 mg/dl) than at the higher doses (630 and 950 mg/dl). Furthermore, ethanol induced apoptosis in a dose-related manner, with peak apoptosis observed at a dose of 630 mg/dl in the case of DNA fragmentation and at 630 and 950 mg/dl in the case of phosphatidylserine translocation to the outer leaflet of the plasma membrane. Ethanol did not induce necrosis at any of the administered doses of ethanol. CONCLUSIONS: Our data suggest that ethanol induces a susceptibility to apoptotic signals at low doses by upregulating the expression of mRNAs for cytotoxic receptors such as Fas/Apo-1 in the developing cerebral cortex. However, ethanol itself specifically induces apoptosis in the developing cerebral cortex only at higher doses.

Animals↗