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Significant Delay (significant + delay)
Selected AbstractsDifferential developmental toxicities of di- n -hexyl phthalate and dicyclohexyl phthalate administered orally to ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2009Anne-Marie Saillenfait Abstract The objective of this study was to evaluate the developmental toxic potential of di- n -hexyl phthalate (DnHP) and dicyclohexyl phthalate (DCHP) in rats. Pregnant Sprague,Dawley rats were exposed to DnHP or DCHP at doses of 0 (olive oil), 250, 500 and 750 mg kg,1 per day, by gavage, on gestational days (GD) 6,20. Maternal food consumption and body weight gain were significantly reduced at 750 mg kg,1 per day of DnHP and at the two high doses of DCHP. Slight changes in liver weight associated with peroxisomal enzyme induction were seen in dams treated with DnHP or DCHP. DnHP caused dose-related developmental toxic effects, including marked embryo mortality at 750 mg kg,1 per day, and presence of malformations (mainly cleft palate, eye defects and axial skeleton abnormalities) and significant decreases in fetal weight at 500 and 750 mg kg,1 per day. Significant delay of ossification and increase in the incidence of skeletal variants (e.g. supernumerary lumbar ribs) also appeared at 250 mg kg,1 per day. DCHP produced fetal growth retardation at 750 mg kg,1 per day, as evidenced by significant reduction of fetal weight. DnHP and DCHP induced a significant and dose-related decrease in the anogenital distance of male fetuses at all doses, and there was a significant increase in the incidence of male fetuses with undescended testis at 500 and 750 mg kg,1 per day of DnHP. In conclusion, DnHP showed clear embryolethality and teratogenicity, but not DCHP. There was evidence that both phthalates could alter the development of the male reproductive system after in utero exposure, DnHP being much more potent than DCHP. Copyright © 2009 John Wiley & Sons, Ltd. [source] The rationale for early intervention in schizophrenia and related disordersEARLY INTERVENTION IN PSYCHIATRY, Issue 2009Merete Nordentoft Abstract Aim: To examine the rationale and evidence supporting an early intervention approach in schizophrenia. Methods: A selective literature review was conducted. Results: During the onset of schizophrenia, there is often a significant delay between the emergence of psychotic symptoms and the initiation of treatment. The average duration of untreated psychosis is around 1,2 years. During this period, brain function may continue to deteriorate and social networks can be irreversibly damaged. Studies have consistently linked longer duration of untreated psychosis with poorer outcomes and this relationship holds even after controlling for the potential confounding variable of premorbid functioning. In Norway, the early Treatment and Intervention in PSychosis study demonstrated that duration of untreated psychosis is amenable to intervention with the combination of educational campaigns and specialized early detection units substantially decreasing the period from onset of symptoms to treatment initiation. Furthermore, recent evidence from the randomized controlled OPUS and the Lambeth Early Onset trial studies have linked phase-specific early interventions to improved outcomes spanning symptoms, adherence to treatment, comorbid drug abuse, relapse and readmission. Some benefits persist after cessation of the intervention. Conclusions: Early intervention in schizophrenia is justified to reduce the negative personal and social impact of prolonged periods of untreated symptoms. Furthermore, phase-specific interventions are associated with improved outcomes, at least in the short term. Further research is needed to establish the optimum duration of such programmes. [source] The Effects of Ascorbic Acid on Penicillin-induced Epileptiform Activity in RatsEPILEPSIA, Issue 7 2007Mustafa Ayyildiz Summary:,Purpose: Epileptic seizure results from excessive discharge in a population of hyperexcitable neurons. A number of studies help to document the effects of active oxygen free radical scavengers such as ,-tocopherol or ascorbic acid (vitamin C). In the present study, we examined the effects of ascorbic acid, at the six different doses, on penicillin-induced epileptiform activity. Methods: A single microinjection of penicillin (2.5 ,l, 500 units, intracortically) into the left sensorimotor cortex induced epileptiform activity within 2,5 min, progressing to full seizure activity lasting ,3,5 h. In the first set of experiments, 30 min after penicillin injection, six different doses of ascorbic acid (25, 50, 100, 200, 400, or 800 mg/kg) were administered intraperitoneally (IP). The other group of animals received the effective dose of ascorbic acid (100 mg/kg, IP) for 7 days. Ascorbic acid administration was stopped 24 h before penicillin treatment. Another group of rats received the effective dose of ascorbic acid (100 mg/kg, IP) 30 min before penicillin treatment. In the second set of experiments, the lipid peroxidation (MDA) and reduced glutathione (GSH) levels of brain were measured in the control, control + ascorbic acid, penicillin, and penicillin + ascorbic acid groups. Results: Ascorbic acid, at the low dose (50, 100 mg/kg, 30 min after penicillin injection), decreased both the frequency and amplitude of penicillin-induced epileptiform activity in rats. Ascorbic acid, at intermediate doses (200, 400 mg/kg, 30 min after penicillin injection), decreased the frequency of epileptiform activity without changing the amplitude. Ascorbic acid, at the lowest dose (25 mg/kg) and highest dose (800 mg/kg) (30 min after penicillin injection), did not change either the frequency or amplitude of epileptiform activity. Ascorbic acid, at the low dose (100 mg/kg) was the most effective dose in changing the frequency and amplitude of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) 30 min before penicillin treatment caused a significant delay in the onset of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) for 7 days did not change the latency of epileptiform activity. The most effective dose of ascorbic acid (100 mg/kg) prevented both the decrease in GSH level and the increase in lipid peroxidation level (MDA) occurring after penicillin-induced epileptiform activity. Conclusions: These data indicate that ascorbic acid has neuroprotective activity against penicillin-induced epileptiform electrocorticogram activity. [source] Impact of Critical Bed Status on Emergency Department Patient Flow and OvercrowdingACADEMIC EMERGENCY MEDICINE, Issue 4 2003Stephen Liu MD Objective: To compare measurements of emergency department (ED) patient flow during periods of acute ED overcrowding and times of normal patient volume (NPV). Methods: Retrospective ED chart review comparing ED flow for patients treated in a tertiary care teaching hospital during periods of ED overcrowding, defined as critical bed status (CBS), and NPV. All periods of CBS during July 2001 were identified. CBS time intervals were matched with NPV times by month, day of the week, time of day, and number of care providers. All patients registered during these matched time intervals were reviewed. Times were collected for each of the following activities: check-in, bed placement, physician assessment, first intervention, and disposition. Corresponding intervals were calculated in minutes. Triage category was used as a marker of illness severity (1 = most severe, 5 = least severe). Descriptive statistics were performed. Results: One hundred eighteen patient charts were reviewed: 61 CBS and 57 NPV. There was no statistical difference in illness severity between the two groups. In the cumulative analysis, patients waited significantly longer for an ED bed (30.4 min, p = 0.01) but did not experience significant delays in other intervals. Triage category analysis revealed no significant difference in triage 2 patients. Intermediate-severity patients (triage 3) waited longer in every interval and significantly longer for physician assessment (30.8 min longer, p < 0.05). Low-severity patients (triage 4) waited longer for an ED bed (40 min, p = 0.02) but did not experience other significant delays. Conclusions: During times of acute overcrowding, the most significant delay occurs awaiting placement in the ED bed. [source] Restoration of C1q levels by bone marrow transplantation attenuates autoimmune disease associated with C1q deficiency in miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Josefina Cortes-Hernandez Abstract C1q deficiency in both humans and mice is strongly associated with autoimmunity. We have previously shown that bone marrow transplantation (BMT) restored C1q levels in C1q-deficient (C1qa,/,) mice. Here, we studied the effect of BMT on autoimmunity in C1qa,/, mice. Following irradiation, young C1qa,/, or wild-type MRL/Mp mice received bone marrow cells (BMC) from strain-matched wild-type or C1qa,/, animals. C1q levels increased rapidly when C1qa,/, mice received BMC from wild-type mice. Conversely, they decreased slowly in wild-type mice transplanted with C1qa,/, BMC. C1qa,/, animals transplanted with C1qa,/, BMC demonstrated accelerated disease when compared with wild-type mice given wild-type BMC. In contrast, a significant delay in the development of autoantibodies and glomerulonephritis was observed in C1qa,/, mice reconstituted with wild-type BMC, and the impaired clearance of apoptotic cells, previously described in C1qa,/, mice, was rectified. Moreover, the autoimmune disease was accelerated in wild-type mice given C1qa,/, BMC compared to animals transplanted with wild-type cells. These results provide supporting evidence that BMT may be a therapeutic option in the treatment of autoimmunity associated with human C1q deficiency. [source] CCL25/CCR9 promotes the induction and function of CD103 on intestinal intraepithelial lymphocytesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2004Anna Ericsson Abstract The integrin CD103 and the chemokine receptor CCR9 are co-expressed on small intestinal CD8+ intraepithelial lymphocytes (IEL), naïve murine CD8+ T cells and by a small population of effector/memory CD8+ T cells, indicating a potential role for CCR9 in regulating CD103 expression and function. Here, we demonstrate that CD103, in contrast to CCR9, is down-regulated on CD8+ T cells following their activation in mesenteric lymph nodes and that effector CD8+ T cells upon initial entry into the small intestinal epithelium are CCR9+CD103,. CD103 was rapidly induced on wild-type CD8+ T cells subsequent to their entry into the small intestinal epithelium, however, CCR9,/, CD8+ T cells exhibited a significant delay in CD103 induction at this site. In addition, the CCR9 ligand, CCL25, that is constitutively expressed in the small intestinal epithelium, induced transient, dose-dependent and pertussis toxin-sensitive CD103-mediated adhesion of CD8+ small intestinal IEL to a murine E-cadherin human Fc (mEFc) fusion protein. Together, these results demonstrate a role for CCR9/CCL25 in promoting the induction and function of CD103 on CD8+ IEL and suggest that this chemokine receptor/chemokine pair may function to regulate lymphocyte-epithelial interactions in the small intestinal mucosa. [source] Altered sensorimotor development in a transgenic mouse model of amyotrophic lateral sclerosisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2004Julien Amendola Abstract Most neurodegenerative diseases become manifest at an adult age but abnormalities or pathological symptoms appear earlier. It is important to identify the initial mechanisms underlying such progressive neurodegenerative disease in both humans and animals. Transgenic mice expressing the familial amyotrophic lateral sclerosis (ALS)-linked mutation (G85R) in the enzyme superoxide dismutase 1 (SOD1) develop motor neuron disease at 8,10 months of age. We address the question of whether the mutation has an early impact on spinal motor networks in postnatal mutant mice. Behavioural tests showed a significant delay in righting and hind-paw grasping responses in mutant SOD1G85R mice during the first postnatal week, suggesting a transient motor deficit compared to wild-type mice. In addition, extracellular recordings from spinal ventral roots in an in vitro brainstem,spinal cord preparation demonstrated different pharmacologically induced motor activities between the two strains. Rhythmic motor activity was difficult to evoke with N -methyl- dl -aspartate and serotonin at the lumbar levels in SOD1G85R mice. In contrast to lumbar segments, rhythmic activity was similar in the sacral roots from the two strains. These results strongly support the fact that the G85R mutation may have altered lumbar spinal motor systems much earlier than previously recognized. [source] Gastric Stasis in Migraine: More Than Just a Paroxysmal Abnormality During a Migraine AttackHEADACHE, Issue 1 2006Objective.,The aim of this article is to evaluate gastric motility and emptying in the ictal and interictal period in migraine. Background.,Nausea is a predominant symptom of migraine and the basis of it is thought to be gastric stasis. Objective methods to establish this are however lacking. We utilized gastric scintigraphy studies to determine gastric motility in the ictal and interictal period of migraine. Methods.,Ten migraine subjects were compared to equal number of age and sex matched controls. Gastric scintigraphy using a standard meal was performed in all control subjects once and in all 10 migraine subjects in the interictal period and nine studies were performed in the ictal period migraine. Results.,The time to half emptying was delayed in migraine ictally (78%) and interictal period (80%) using normative data at this institution. Gastric stasis was less pronounced ictally (149.9 minutes) compared to interictal period (188.8 minutes). There was a significant delay compared to nonmigrainous controls (migraine 188.8 minutes vs normal controls 111.8 minutes; P < .05). These data were replicated in percentage of radioactive material remaining in the stomach at 2 hours. Conclusions.,Contrary to previous belief, this study has demonstrated that migraineurs suffer from gastric stasis both during and outside an acute migraine attack. This may suggest that migraineurs may have an abnormal autonomic function compared to nonmigrainous controls. The potential role of this in pathophysiology of migraine is discussed and avenues for further investigations are explored. [source] Cooperative antitumor effects of vitamin D3 derivatives and rosemary preparations in a mouse model of myeloid leukemiaINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Hagar Sharabani Abstract 1,,25-dihydroxyvitamin D3 (1,25D3) is a powerful differentiation agent, which has potential for treatment of myeloid leukemias and other types of cancer, but the calcemia produced by pharmacologically active doses precludes the use of this agent in the clinic. We have shown that carnosic acid, the major rosemary polyphenol, enhances the differentiating and antiproliferative effects of low concentrations of 1,25D3 in human myeloid leukemia cell lines (HL60, U937). Here we translated these findings to in vivo conditions using a syngeneic mouse leukemia tumor model. To this end, we first demonstrated that as in HL60 cells, differentiation of WEHI-3B D, murine myelomonocytic leukemia cells induced by 1 nM 1,25D3 or its low-calcemic analog, 1,25-dihydroxy-16-ene-5,6-trans-cholecalciferol (Ro25-4020), can be synergistically potentiated by carnosic acid (10 ,M) or the carnosic acid-rich ethanolic extract of rosemary leaves. This effect was accompanied by cell cycle arrest in G0+G1 phase and a marked inhibition of cell growth. In the in vivo studies, i.p. injections of 2 ,g Ro25-4020 in Balb/c mice bearing WEHI-3B D, tumors produced a significant delay in tumor appearance and reduction in tumor size, without significant toxicity. Another analog, 1,25-dihydroxy-16,23Z-diene-20-epi-26,27-hexafluoro-19-nor-cholecalciferol (Ro26-3884) administered at the same dose was less effective than Ro25-4020 and profoundly toxic. Importantly, combined treatment with 1% dry rosemary extract (mixed with food) and 1 ,g Ro25-4020 resulted in a strong cooperative antitumor effect, without inducing hypercalcemia. These results indicate for the first time that a plant polyphenolic preparation and a vitamin D derivative can cooperate not only in inducing leukemia cell differentiation in vitro, but also in the antileukemic activity in vivo. These data may suggest novel protocols for chemoprevention or differentiation therapy of myeloid leukemia. © 2006 Wiley-Liss, Inc. [source] Inherent limitations and control design for camless engine idle speed dynamicsINTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONTROL, Issue 11 2001Yan Wang Abstract The idle speed control problem of a spark-ignited engine equipped with a camless valvetrain is considered. The camless valvetrain allows control of the individual intake and exhaust valves of each cylinder and can be used to achieve unthrottled operation, and consequently, optimize the engine performance. We formulate the speed control problem for this engine and show that it exhibits unstable open-loop behaviour with a significant delay in the feedback loop. The instability is intrinsic to the unthrottled operation and specific to the camless actuation used to achieve the unthrottled operation. The delay is caused by the discrete combustion process and the sensor/computer/actuator interface. We demonstrate the inherent system limitations associated with the unstable dynamics and the delay and provide insight on the structural (plant) design that can alleviate these limitations. Finally, stabilizing controllers using classical and modern robust design techniques are presented and tested on a nonlinear simulation model. Copyright © 2001 John Wiley & Sons, Ltd. [source] Connexin40-Deficient Mice Exhibit Atrioventricular Nodal and Infra-Hisian Conduction AbnormalitiesJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2000BRIAN A. VANDERBRINK B.S. AV Nodal and Infra-Hisian Conduction in Cx40 Mice. Introduction: Previous electrophysiologic investigations have described AV conduction disturbances in connexin4(Cx40)-deficient mice. Because expression or(Cx40 occurs predominantly in the atria and His-Purkinje system of the mouse heart, the AV conduction disturbances were thought to be secondary to disruption in His-Pnrkinje function. However, the lack of a His-bundle electrogram recording in the mouse has limited further investigation of the importance of Cx40. Using a novel technique to record His-bundle recordings in Cx40-deficient mice, we define the physiologic importance of defciencies in Cx40. Methods and Results: Ten Cx40 -/- mice and 11 Cx40+/+ controls underwent a blinded, in vivo, closed chest electrophysiology study at 9 to 12 weeks of age. In the Cx40+/+ mice, the PR interval was significantly longer compared with Cx40+/+ mice (44.6 ± 6.4 msec vs 36.0 ± 4.1 msec, P = 0.002). Not only the HV interval (14.0 ± 3.0 msec vs 10.4 ± 1.2 msec, P = 0.003) but also the AH interval (33.2 ± 4.8 msec vs 27.1 ± 3.7 msec, P = 0.006), AV Wenckebach cycle lengths, and AV nodal effective and functional refractory periods were prolonged in Cx40 -/- compared with Cx40+/+ mice. Conclusion: Cx40-deficient mice exhibit significant delay not only in infra-Hisian conduction, as would be expected from the expression of Cx40 in the His-Purkinje system but also in the electrophysiologic parameters that reflect AV nodal conduction. Our data suggest a significant role of Cx40 in atrionodal conduction and/or in proximal His-bundle conduction, [source] Sperm surface arylsulfatase A can disperse the cumulus matrix of cumulus oocyte complexes,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2007Alexander Wu Cumulus cell layers of expanded cumulus oocyte complexes (COCs) are interlinked with networks of hyaluronic acid, chondroitin sulfate B proteoglycans and link proteins, and they can be dispersed by sperm surface hyaluronidases. In this report, we showed that arylsulfatase A (AS-A), existing on the sperm head surface, also had this dispersion action. Purified AS-A free of protease, hyaluronidase and chondroitinase activities could disperse the cumulus matrix of expanded COCs. However, this COC dispersion action was not associated with AS-A desulfation activity, assayed by using p -nitrocatecholsulfate (artificial substrate). COCs incubated for 1 h with sperm pretreated with anti-AS-A IgG in the presence of apigenin (a hyaluronidase inhibitor) did not exhibit matrix dispersion, whereas several cumulus layers were already dispersed in COCs incubated with sperm pretreated with preimmune IgG. Furthermore, sperm from AS-A null mice showed a significant delay in COC dispersion, compared with wild-type sperm. Within 1 h of sperm-COC co-incubation, the size of COCs incubated with AS-A null sperm was 65% of the original dimension, whereas that of COCs inseminated with wild-type sperm was only 17%. A further delay in COC dispersion by AS-A(,/,) mouse sperm was observed when apigenin was present in the co-incubation. We also showed for the first time that AS-A had a specific affinity for chondroitin sulfate B, a component of cumulus matrix proteoglycan networks; this might provide a mechanism of cumulus matrix destabilization induced by sperm surface AS-A. J. Cell. Physiol. 213: 201,211, 2007. © 2007 Wiley-Liss, Inc. [source] Grazing history versus current grazing: leaf demography and compensatory growth of three alpine plants in response to a native herbivore (Ochotona collaris)JOURNAL OF ECOLOGY, Issue 2 2002Eliot J. B. McIntire Summary 1 We measured leaf births, leaf deaths and leaf length of three alpine perennial species, Kobresia myosuroides, Erigeron humilis and Oxytropis nigrescens, from sites with different grazing histories (strong or weak) in response to two levels of current season grazing (present or absent) by collared pikas (Ochotona collaris), a small lagomorph, in the south-west Yukon. 2 All three species appeared to tolerate the removal of 58,61% of summer leaf production under natural conditions. Grazing history, which was defined by the location of plants located either < 2 m or > 6 m from boulderfields with a history of occupation by pikas, was the most significant factor determining shifts in leaf births and leaf deaths following herbivory. 3 The only detectable influence of current season herbivory for any measured species was a reduction of leaf length of Kobresia. 4 A comparison of historically grazed with historically ungrazed plants indicated several changes in leaf demography and morphology. Kobresia leaves were generally shorter and had higher rates of production of new leaves. Oxytropis had higher rates of new leaf production. Erigeron had fewer leaf births throughout the summer, but showed a large and highly significant delay in the timing of leaf senescence. 5 These responses can be largely understood as strategies to avoid the predictable intensive late season foraging that is characteristic of pikas. Morphological mechanisms allow these species to tolerate and, more importantly for the herbivore, persist under heavy and chronic grazing. [source] Neonatal Lipopolysaccharide Exposure Delays Puberty and Alters Hypothalamic Kiss1 and Kiss1r mRNA Expression in the Female RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2009A. M. I. Knox Immunological challenge experienced in early life can have long-term programming effects on the hypothalamic-pituitary-adrenal axis that permanently influence the stress response. Similarly, neonatal exposure to immunological stress enhances stress-induced suppression of the hypothalamic-pituitary gonadal (HPG) axis in adulthood, but may also affect earlier development, including the timing of puberty. To investigate the timing of the critical window for this programming of the HPG axis, neonatal female rats were injected with lipopolysaccharide (LPS; 50 ,g/kg i.p.) or saline on postnatal days 3 + 5, 7 + 9, or 14 + 16 and monitored for vaginal opening and first vaginal oestrus as markers of puberty. We also investigated the effects of neonatal programming on the development of the expression patterns of kisspeptin (Kiss1) and its receptor (Kiss1r) in hypothalamic sites known to contain kisspeptin-expressing neuronal populations critical to reproductive function: the medial preoptic area (mPOA) and the arcuate nucleus in neonatally-stressed animals. We determined that the critical period for a significant delay in puberty as a result of neonatal LPS exposure is before 7 days of age in the female rat, and demonstrated that Kiss1, but not Kiss1r mRNA, expression in the mPOA is down-regulated in pre-pubertal females. These data suggest that the mPOA population of kisspeptin neurones play a pivotal role in controlling the onset of puberty, and that their function can be affected by neonatal stress. [source] Disturbances in melatonin and core body temperature circadian rhythms after minimal invasive surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2007I. Gögenur Background:, Sleep disturbances, fatigue and reduced general well-being frequently occur after minimal invasive surgery. The circadian rhythms of melatonin and core body temperature are central to the regulation of normal sleep. The aim of this study was to assess changes in these circadian rhythms after laparoscopic cholecystectomy. Methods:, Twelve women were studied before and after laparoscopic cholecystectomy. The major urinary melatonin metabolite, 6-sulphatoxymelatonin (aMT6s), and the core body temperature were measured for 1 day before and 1 day after surgery. The basal and maximum secretion of aMT6s were determined, as well as the timing and amplitude of aMT6s and the temperature rhythm. The patients' rest,activity and calculated sleep parameters were assessed by actigraphy. Results:, A significant delay in the timing of aMT6s rhythm was observed after surgery [median (range) peak time of aMT6s: after surgery, 05:49 h (02:57,08:23 h); before surgery, 04:32 h (02:18,06:49 h); P, 0.05]. The amplitude of the aMT6s rhythm was also significantly decreased after surgery [after surgery, 7.1 ng aMT6s/mg creatinine (1,15.9 ng); before surgery, 13.2 ng aMT6s/mg creatinine (2.9,22.7 ng); P, 0.005]. There was almost a12-h phase delay of the core body temperature rhythm after surgery [peak time: before surgery, 17:39 h (15:17,22:06 h); after surgery, 05:14 h (03:24,21:43 h); P, 0.01]. Conclusions:, Following laparoscopic cholecystectomy, there was a delay in the timing of the aMT6s rhythm and a decreased evening decline in the temperature rhythm. [source] Age-Induced Neuropathy In RatsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000S Yagihashi We studied the effects of exogenously administered advanced glycation end-products (AGE) on the peripheral nerve function and structure in normal rats. Normal Wistar rats aged 6 weeks were injected intraperitoneally with purified AGE (20 mg/kg/day) produced by incubation of glucose with bovine serum albumin (BSA) for 12 weeks. Control rats were treated with BSA alone. One of AGE-treated groups was co-treated with 50 mg/kg aminoguanidine (AG). During the experimental period, body weight and blood glucose levels were not affected in AGE-treated rats. Serum AGE levels were elevated two fold in AGE-treated group whereas BSA treated rats maintained normal levels, whereas tissue AGE levels in sciatic nerve were not increased in treated group. AG did not alter the levels of serum AGE. AGE-treated rats exhibited significant delay of motor nerve conduction velocity by 30% and reduction of sciatic nerve in Na,K-ATPase activity by 25% in AGE-treated rats. AG treatment significantly inhibited these changes. Immunostains on the cross-sections of sciatic nerve demonstrated significant increase in cells positive for 8 hydroxy-deoxyguanosine, a marker of oxidative stress-induced DNA injury, in AGE-treated group. AG treatment significantly inhibited this reaction. There was no difference in morphometric data on myelinated fibers in sural nerve among the experimental groups. AGE-injected rats thus showed the neuropathic changes, similar to those found in experimentally-induced diabetic animals and it is therefore suggested that AGE have a pathogenetic role in the development of diabetic neuropathy through induction of excessive oxidative stress. Supported by Juvenile Diabetes Foundation International (1-2000-263), Japan Diabetes Foundation, Japanese Ministry of Science, Education, Sports and Culture. [source] Craniofacial and dental findings in cystinosisORAL DISEASES, Issue 5 2010CW Bassim Oral Diseases (2010) 16, 488,495 Objectives:, Cystinosis is a rare autosomal recessive lysosomal storage disorder with developmental and mineralization anomalies as part of its clinical presentation. The objective of this study was to provide the first systematic assessment of the craniofacial and dental characteristics associated with cystinosis. Study Design:, Oral and radiographic evaluations were performed on 73 patients with cystinosis. Analyses of cephalometry (n = 20), taurodontism (n = 47), caries (n = 47), enamel defects (n = 48), soft tissue anomalies (n = 48), and dental age (n = 41) were performed on the cystinosis group, and compared with age- and sex-comparable controls or standards. Results:, Cystinosis patients manifested relative mandibular deficiency, an increased facial height, and a reduced airway space. Taurodontism and enamel defects were significantly more prevalent in cystinosis patients compared with controls (P < 0.0001 and P = 0.027, respectively). Children (aged <15 years) with cystinosis also demonstrated a significant delay, of almost 9 months, of their dental development (P < 0.001). Conclusion:, Novel craniofacial and dental features are associated with cystinosis. Craniofacial deficiencies may influence the swallowing and respiratory complications seen in cystinosis. Renal pathology and associated mineral imbalance may explain the dental root and enamel anomalies found in cystinosis patients; the developmental delays in cystinosis include delayed dental formation. [source] Papaya fruit softening, endoxylanase gene expression, protein and activityPHYSIOLOGIA PLANTARUM, Issue 3 2007Ashariya Manenoi Papaya (Carica papaya L.) cell wall matrix polysaccharides are modified as the fruit starts to soften during ripening and an endoxylanase is expressed that may play a role in the softening process. Endoxylanase gene expression, protein amount and activity were determined in papaya cultivars that differ in softening pattern and in one cultivar where softening was modified by the ethylene receptor inhibitor 1-methylcyclopropene (1-MCP). Antibodies to the endoxylanase catalytic domain were used to determine protein accumulation. The three papaya varieties used in the study, ,Line 8', ,Sunset', and ,Line 4-16', differed in softening pattern, respiration rate, ethylene production and showed similar parallel relationships during ripening and softening in endoxylanase expression, protein level and activity. When fruit of the three papaya varieties showed the respiratory climacteric and started to soften, the level of endoxylanase gene expression increased and this increase was related to the amount of endoxylanase protein at 32 kDa and its activity. Fruit when treated at less than 10% skin yellow stage with 1-MCP showed a significant delay in the respiratory climacteric and softening, and reduced ethylene production, and when ripe was firmer and had a ,rubbery' texture. The 1-MCP-treated fruit that had the ,rubbery' texture showed suppressed endoxylanase gene expression, protein and enzymatic activity. Little or no delay occurred between endoxylanase gene expression and the appearance of activity during posttranslational processing from 65 to 32 kDa. The close relationship between endoxylanase gene expression, protein accumulation and activity in different varieties and the failure of the 1-MCP-treated fruit to fully soften, supported de novo synthesis of endoxylanase, rapid posttranslation processing and a role in papaya fruit softening. [source] Analysis of protein profiles of genetically modified potato tubers by matrix-assisted laser desorption/ionization time-of-flight mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 5 2003M. Careri Traceability of genetically modified (GM) foods demands the development of appropriate reliable techniques in order to identify and quantify peptide or nucleic acid residues in GM plants and food products through the food chain. In this study the applicability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was demonstrated for the characterization of proteins of transformed and untransformed potato (Solanum Tuberosum L.) tubers. In GM tubers the expression level of the G1-1 gene, which regulates transition from dormancy to sprouting tubers, was inhibited by antisense technology. The analysis of antisense transformed lines showed that several of them exhibited a significant delay in sprouting relative to the control lines, in accordance with a decrease in the transcript level. Preliminary attempts to compare the protein patterns obtained from transformed and control lines using traditional electrophoresis were not able to reveal differences in the low-kDa range. Instead, MALDI-TOFMS applied to total peptide extract without any purification was able to distinguish spectral patterns of transformed and untransformed lines. In particular, several characteristic peaks from m/z 4373 to 4932 were detected only in the mass spectra of GM tuber samples. Copyright © 2003 John Wiley & Sons, Ltd. [source] Optimal Valuation of Claims on Noisy Real Assets: Theory and an ApplicationREAL ESTATE ECONOMICS, Issue 3 2002Paul D. Childs A theory for valuing claims on noisy real assets is developed and applied. Central to the theory is determination of the dynamics for the best estimate of real asset value. The dynamics of the value estimate are shown to differ from the dynamics of the true asset value only in the arrival rate of information. The rate of information arrival in the value estimate can be faster or slower than information arrival in the true asset value, which can lead to unexpected outcomes in the valuation and exercise of options on noisy real assets. The theory we develop is illustrated through an application. An imperfectly competitive market for real estate development is examined, in which agents compete over the timing of lead investment. Information spillover and free,rider incentives are shown to cause significant delay in lead investment. Delay together with a competitive response once lead investment has occurred explain observed patterns of development in gentrified urban land markets and multistage development projects. [source] The Effects of Oral Administration of D-Modafinil on Male Rat Ejaculatory BehaviorTHE JOURNAL OF SEXUAL MEDICINE, Issue 1pt1 2010Lesley Marson PhD ABSTRACT Introduction., Premature ejaculation (PE) is one of the most common forms of male sexual dysfunction. Examination of various classes of drugs on ejaculation latency would provide further opportunities for drug development in this field. Aim., This study was conducted to examine the effects of the d-isomer of modafinil (d-modafinil) on ejaculatory behavior in a rat model. Methods., Male sexual behavior in the rat was examined after acute oral administration of d-modafinil (10 mg/kg, 30 mg/kg, and 100 mg/kg) in copulation studies with receptive females. Main Outcome Measures., The latency to ejaculation, post-ejaculatory interval, and the frequency of mounting behavior were measured. Results d-modafinil (30 mg/kg and 100 mg/kg) produced a significant delay in ejaculation. The delay in ejaculation was accompanied by an increase in the number of intromissions without any change in the mount or intromission latency. The possible mechanisms of action of d-modafinil to produce this delay in ejaculation are discussed. Conclusions., These results demonstrate that acute oral administration of d-modafinil can lengthen the latency to ejaculation in rats without suppressing sexual behavior. The greatest delay in ejaculation was observed in animals with shorter baseline ejaculatory latencies. Investigation into new classes of drugs that modulate ejaculation may provide new therapeutic options for treating PE. Marson L, Yu G, and Farber NM. The effects of oral administration of d-modafinil on male rat ejaculatory behavior. J Sex Med 2010;7:70,78. [source] A role for caleosin in degradation of oil-body storage lipid during seed germinationTHE PLANT JOURNAL, Issue 6 2006Marianne Poxleitner Summary Caleosin is a Ca2+ -binding oil-body surface protein. To assess its role in the degradation of oil-bodies, two independent insertion mutants lacking caleosin were studied. Both mutants demonstrated significant delay of breakdown of the 20:1 storage lipid at 48 and 60 h of germination. Additionally, although germination rates for seeds were not affected by the mutations, mutant seedlings grew more slowly than wild type when measured at 48 h of germination, a defect that was corrected with continued growth for 72 and 96 h in the light. After 48 h of germination, wild-type central vacuoles had smooth contours and demonstrated internalization of oil bodies and of membrane containing , - and , -tonoplast intrinsic proteins (TIPs), markers for protein storage vacuoles. In contrast, mutant central vacuoles had distorted limiting membranes displaying domains with clumps of the two TIPs, and they contained fewer oil bodies. Thus, during germination caleosin plays a role in the degradation of storage lipid in oil bodies. Its role involves both the normal modification of storage vacuole membrane and the interaction of oil bodies with vacuoles. The results indicate that interaction of oil bodies with vacuoles is one mechanism that contributes to the degradation of storage lipid. [source] Days to criterion as an indicator of toxicity associated with human Alzheimer amyloid-, oligomersANNALS OF NEUROLOGY, Issue 2 2010Sam Gandy MD Objective Recent evidence suggests that high molecular weight soluble oligomeric A, (oA,) assemblies (also known as A,-derived diffusible ligands, or ADDLs) may represent a primary neurotoxic basis for cognitive failure in Alzheimer disease (AD). To date, most in vivo studies of oA,/ADDLs have involved injection of assemblies purified from the cerebrospinal fluid of human subjects with AD or from the conditioned media of A,-secreting cells into experimental animals. We sought to study the bioactivities of endogenously formed oA,/ADDLs generated in situ from the physiological processing of human amyloid precursor protein (APP) and presenitin1 (PS1) transgenes. Methods We produced and histologically characterized single transgenic mice overexpressing APPE693Q or APPE693Q X PS1,E9 bigenic mice. APPE693Q mice were studied in the Morris water maze (MWM) task at 6 and 12 months of age. Following the second MWM evaluation, mice were sacrificed, and brains were assayed for A,total, A,40, A,42, and oA,/ADDLs by enzyme-linked immunosorbent assay (ELISA) and were also histologically examined. Based on results from the oA,/ADDL ELISA, we assigned individual APPE693Q mice to either an undetectable oA,/ADDLs group or a readily detectable oA,/ADDLs group. A days to criterion (DTC) analysis was used to determine delays in acquisition of the MWM task. Results Both single transgenic and bigenic mice developed intraneuronal accumulation of APP/A,, although only APPE693Q X PS1,9 bigenic mice developed amyloid plaques. The APPE693Q mice did not develop amyloid plaques at any age studied, up to 30 months. APPE693Q mice were tested for spatial learning and memory, and only 12-month-old APPE693Q mice with readily detectable oA,/ADDLs displayed a significant delay in acquisition of the MWM task when compared to nontransgenic littermates. Interpretation These data suggest that cerebral oA,/ADDL assemblies generated in brain in situ from human APP transgenes may be associated with cognitive impairment. We propose that a DTC analysis may be a sensitive method for assessing the cognitive impact in mice of endogenously generated oligomeric human A, assemblies. ANN NEUROL 2010 [source] WILL THE DILEMMA OF EVIDENCE-BASED SURGERY EVER BE RESOLVED?ANZ JOURNAL OF SURGERY, Issue 9 2006Ned S. Abraham Exponents of evidence-based medicine do not undermine the importance of clinical expertise and skills, but they emphasize that decision-making in medicine should be based on the best available evidence derived from the systematic analysis of observations made in an objective, unbiased and a reproducible fashion. The randomized controlled trial (RCT) is the most scientifically rigorous means of hypothesis testing in epidemiology. Discrepancies between established surgical and other interventions and best available evidence are common. These can be in the form of significant delay in adopting a new intervention despite strong supportive evidence, adopting an intervention before supportive evidence becomes available for reasons of novelty or pear pressure and the lack of supportive evidence for many established common practices. This is compounded further by the paucity of good quality evidence for most surgical procedures. This is arguably because of the inherent difficulties in conducting surgical RCT. The practical, ethical and financial ramifications are complex and the nature of surgical disease often compromise the chances of success or completion of RCT. Carrying out surgical RCT may have more implications on the clinician's authority, autonomy and income and their results are more likely to be influenced by his/her expertise and competence than medical RCT. Furthermore, the success of surgical RCT is often jeopardized by very low recruitment rates. The aim of this study is to discuss the dilemma of producing evidence in surgery. [source] Skin wound healing in diabetic ,6 integrin-deficient miceAPMIS, Issue 10 2010JASPER N. JACOBSEN Jacobsen JN, Steffensen B, Häkkinen L, Krogfelt KA, Larjava HS. Skin wound healing in diabetic ,6 integrin-deficient mice. APMIS 2010; 118: 753,64. Integrin ,v,6 is a heterodimeric cell surface receptor, which is absent from the normal epithelium, but is expressed in wound-edge keratinocytes during re-epithelialization. However, the function of the ,v,6 integrin in wound repair remains unclear. Impaired wound healing in patients with diabetes constitutes a major clinical problem worldwide and has been associated with the accumulation of advanced glycated endproducts (AGEs) in the tissues. AGEs may account for aberrant interactions between integrin receptors and their extracellular matrix ligands such as fibronectin (FN). In this study, we compared healing of experimental excisional skin wounds in wild-type (WT) and ,6-knockout (,6,/,) mice with streptozotocin-induced diabetes. Results showed that diabetic ,6,/, mice had a significant delay in early wound closure rate compared with diabetic WT mice, suggesting that ,v,6 integrin may serve as a protective role in re-epithelialization of diabetic wounds. To mimic the glycosylated wound matrix, we generated a methylglyoxal (MG)-glycated variant of FN. Keratinocytes utilized ,v,6 and ,1 integrins for spreading on both non-glycated and FN-MG, but their spreading was reduced on FN-MG. These findings indicated that glycation of FN and possibly other integrin ligands could hamper keratinocyte interactions with the provisional matrix proteins during re-epithelialization of diabetic wounds. [source] Cytological studies on induced meiogynogenesis in Japanese flounder Paralichthys olivaceus (Temminck et Schlegel)AQUACULTURE RESEARCH, Issue 6 2009Jilun Hou Abstract The cytological process of induced gynogenetic development and subsequent chromosome duplication by a cold shock treatment was observed in Japanese flounder Paralichthys olivaceus (Temminck et Schlegel). Mature eggs were at the metaphase of the second meiosis when inseminated with ultraviolet (UV)-irradiated sperm of red sea bream Pagrus major. After the beginning of cold shock treatment, the previously visible spindle became invisible, probably due to the side effect caused by cold shock treatment. The chromosomes at the centre of the metaphase plate were condensed. This condition continued during the duration of the cold shock treatment and several minutes after it. The release of the second polar body was blocked and it developed into a female-like pronucleus. Then, it fused with the female pronucleus to generate a diploid zygotic nucleus, and the egg exhibited the first mitosis. Consequently, the haploid female chromosome set of the egg was doubled by the inhibition of the second polar body release. There was a significant delay in developmental time in the gynogenetic eggs when compared with that in the normal eggs. From the time of insemination to early cleavage, the UV-irradiated heterospecific sperm nucleus remained condensed. [source] Use of Simulation Technology in Forensic Medical EducationACADEMIC EMERGENCY MEDICINE, Issue 2009Heather Rozzi Although the emergency department often provides the first and only opportunity to collect forensic evidence, very few emergency medicine residencies have a forensic medicine curriculum in place. Most of the existing curricula are composed only of traditional didactics. However, as with any lecture-based education, there may be a significant delay between the didactic session and clinical application. In addition, traditional curricula lack the opportunity for residents to practice skills including evidence collection, documentation, and use of a colposcope. At York Hospital, we have developed a forensic curriculum which consists of both traditional lectures and practical experience in our Medical Simulation Center. As part of their educational conference series, residents receive presentations on domestic violence, child abuse, elder abuse, evidence collection, sexual assault, ballistics, pattern injuries, documentation, forensic photography, and court testimony. Following these presentations, residents have the opportunity to apply their knowledge of forensic medicine in the Simulation Center. First, they interview a standardized patient. They then utilize the mannequins in the Simulation Center to practice evidence collection, photo documentation, and use of our specialized forensic medicine charts. After evidence collection and documentation, the residents provide safety planning for the standardized patients. Each portion is videotaped, and each resident is debriefed by victim advocates, experienced sexual assault nurse examiners, and emergency department faculty. The use of simulation technology in resident education provides the opportunity to practice the skills of forensic medicine, ultimately benefiting patients, residents, and law enforcement, and permitting teaching and evaluation in all six core competency areas. [source] SIP message prioritization and its applicationsBELL LABS TECHNICAL JOURNAL, Issue 1 2006Harold Batteram Session Initiation Protocol (SIP) signaling is an integral part of the IP Multimedia Subsystem (IMS) to support services such as Voice over IP (VoIP), multimedia sessions, presence, and instant messaging (IM). All of these services share a common SIP signaling infrastructure. In spite of careful network engineering, SIP network elements may experience high-load situations, in which SIP messages may experience too much delay or even get dropped. This paper addresses how such undesired high-load situations can be handled effectively by introducing a message prioritization mechanism in SIP servers. To validate the mechanism, it has been implemented in a highperformance JAIN*-SIP-compliant Java* SIP stack. This SIP stack incorporates several other innovations, such as a very efficient SIP message parser, and it can be used for a variety of SIP-based applications. Its design enables service providers to define custom message prioritization and rejection strategies based on SIP message characteristics, system state, and statistics. Measurements show that high-priority emergency messages can indeed be serviced without significant delay or loss in a high-load situation. The concept of and techniques for SIP prioritization are the subjects of a Lucent Technologies patent application. © 2006 Lucent Technologies Inc. [source] Preventive effects of drinking green tea on cancer and cardiovascular disease: Epidemiological evidence for multiple targeting preventionBIOFACTORS, Issue 1-4 2000Kei Nakachi Abstract The significance of drinking green tea in prevention of two of the main lifestyle-related diseases, cancer and cardiovascular disease, was demonstrated in terms of a prospective cohort study on a total of 8,552 general residents in Saitama Prefecture, Japan. On the basis of the follow-up study, we revealed decreased relative risk of cancer incidence for those consuming over 10 cups a day, compared with those consuming below 3 cups: 0.54 (95% men, 0.57 (0.34,0.98) for women, and 0.59 (0.35,0.98) for both sexes. Furthermore, a significant delay in cancer onset was associated with increased consumption of green tea. Next, decreased relative risk of death from cardiovascular disease was 0.58 (0.34,0.99) for men, 0.82 (0.49,1.38) for women, and 0.72 (0.60,1.04) for members of both sexes consuming over 10 cups a day. Finally, we evaluated the life-prolonging effects of drinking green tea on cumulative survival, using the life table. [source] Down regulation of BRCA2 causes radio-sensitization of human tumor cells in vitro and in vivoCANCER SCIENCE, Issue 4 2008Dong Yu In order to study the role of BRCA2 protein in homologous recombination repair and radio-sensitization, we utilized RNA interference strategy in vitro and in vivo with human tumor cells. HeLa cells transfected with small-interfering BRCA2 NA (BRCA2 siRNA) (Qiagen) as well as negative-control siRNA for 48 h were irradiated, and several critical end points were examined. The radiation cell survival level was significantly reduced in HeLa cells with BRCA2 siRNA when compared with mock- or negative-control siRNA transfected cells. DNA double strand break repair as measured by constant field gel-electrophoresis showed a clear inhibition in cells with BRCA2 siRNA, while little inhibition was observed in cells with negative control siRNA. Our immuno-staining experiments revealed a significant delay in Rad51 foci formation in cells with BRCA2 siRNA when compared with the control populations. However, none of the non-homologous end joining proteins nor the phosphorylation of DNA-dependent protein kinase catalytic subunit was affected in cells transfected with BRCA2 siRNA. In addition, the combined treatment with radiation and BRCA2 siRNA in xenograft model with HeLa cells showed an efficient inhibition of in vivo tumor growth. Our results demonstrate down-regulation of BRCA2 leads to radio-sensitization mainly through the inhibition of homologous recombination repair type double-strand break repair; a possibility of using BRCA2 siRNA as an effective radiosensitizer in tumor radiotherapy may arise. (Cancer Sci 2008; 99: 810,815) [source] | ||||||||||||||||||||||||||||||||||||||||