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Selected AbstractsMultiple P2 Receptors Contribute to a Transient Increase in Intracellular Ca2+ Concentration in Atp-Stimulated Rat Brown AdipocytesEXPERIMENTAL PHYSIOLOGY, Issue 6 2002Mariko Omatsu-Kanbe Extracellular ATP in micromolar concentrations evokes a transient elevation in intracellular free Ca2+ concentration ([Ca2+]i), which arises primarily from a release of Ca2+ from intracellular stores in rat brown adipocytes. We investigated the mechanisms underlying this transient nature of [Ca2+]i elevation during exposure to ATP by using fura-2 fluorescence measurements together with the P2 receptor antagonists pyridoxal-phosphate-6-azophenyl-2,,4,-disulfonic acid (PPADS) and suramin. Extracellular ATP (10 ,M) almost completely depressed the thapsigargin (100 nM)-evoked [Ca2+]i elevation mediated through store-operated Ca2+ entry. The inhibitory effect of ATP was antagonized by PPADS with IC50 of 0.7 ,M. In the presence of PPADS at concentrations of more than 5 ,M, the ATP-induced [Ca2+]i elevation became sustained during the entire duration of the agonist application, although the magnitude of the sustained [Ca2+]i elevation was reduced in a concentration-dependent manner by PPADS with an IC50 of 200 ,M. In contrast, the ATP-induced [Ca2+]i elevation was blocked by suramin in a concentration range similar to that required to antagonize the inhibitory effect of ATP on the store-operated pathway. These results suggest that the [Ca2+]i responses to extracellular ATP in rat brown adipocytes are mediated through the activation of at least two distinct P2 receptors exhibiting different sensitivities to PPADS but similar sensitivities to suramin. Extracellular ATP stimulates the PPADS-resistant P2 receptor to mobilize intracellular Ca2+ stores, which is probably followed by the activation of store-operated Ca2+ entry. Extracellular ATP, however, would inhibit this Ca2+ entry process through the stimulation of the PPADS-sensitive P2-receptor, which may underlie the transient nature of [Ca2+]i elevation in response to extracellular ATP. [source] Napoleon's Lost Legions: French Prisoners of War in Britain, 1803,1814HISTORY, Issue 295 2004GAVIN DALY During the Napoleonic Wars, over 100,000 French prisoners of war were held captive in Britain. These prisoners remain a marginal group in the military history of the period, yet they represent a key turning point in the history of European prisoners of war, and their predicament offers insights into the nature of the French Revolution. This article considers the treatment and experiences of French prisoners, and in particular seeks to understand the circumstances surrounding their long-term captivity. Unlike eighteenth-century prisoners of war, prisoners of the Napoleonic Wars remained captive for the duration of the conflict, unable to return home through the traditional means of prisoner exchange or officer parole. This radical departure from the past gave rise to the modern practice of interning prisoners of war for the entire duration of a war. This historic shift was, on the one level, a result of the actions of one man , Napoleon Bonaparte. Yet, as this article highlights, it must also be understood as part of the long-term social and cultural legacy of the French Revolution. [source] Long-Term Protective Effects of Zoledronic Acid on Cancellous and Cortical Bone in the Ovariectomized Rat,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2008Jürg A Gasser PhD Abstract Current bisphosphonate therapies effectively prevent bone loss in postmenopausal women. We studied the effect of a single intravenous dose of ZOL in ovariectomized rats. Protection from bone loss was dose dependent, lasting for up to 32 weeks, supporting the rationale for an annual intravenous dosing regimen of ZOL for treatment of postmenopausal osteoporosis. Introduction: Once-yearly dosing with zoledronic acid (ZOL) 5 mg can increase BMD and reduce fracture rate in postmenopausal women with low BMD. The primary objective of this study was to determine the duration of bone protective effects of a single dose of ZOL in ovariectomized rats, an animal model of postmenopausal osteopenia. Secondary objectives were to determine the effects on bone turnover and mechanical properties. Materials and Methods: Female Wistar rats (10 per group) received single intravenous doses of ZOL 0.8, 4, 20, 100, or 500 ,g/kg, alendronate 200 ,g/kg, or isotonic saline 4 days before bilateral ovariectomy. Sham-operated controls were pretreated with saline. Mass and density of cancellous and cortical bone (pQCT) were measured at 4-wk intervals for 32 wk. Bone architecture (,CT), bone formation dynamics (fluorochrome label-based histomorphometry), and biomechanical strength in compression testing were also assessed at 32 wk. Results: Ovariectomy-associated BMD loss was significantly attenuated for 32 wk by ZOL ,4 ,g/kg for total BMD, ZOL ,20 ,g/kg for cortical BMD, and ZOL ,4 ,g/kg for cancellous BMD (p < 0.01 versus ovariectomized controls). Alendronate 200 ,g/kg was of equivalent potency to ZOL 20 ,g/kg. Ovariectomy-associated decreases in trabecular architectural parameters were dose-dependently attenuated by ZOL. Alendronate 200 ,g/kg was equivalent to ZOL 20 ,g/kg. The bone resorption marker TRACP5b indicated transient suppression of elevated osteoclast activity by ZOL relative to OVX-rats even at the lowest dose of 0.8 ,g/kg, whereas at 100,500 ,g/kg, the effect was significant relative to the OVX control for the entire duration of the study of 32 wk. Bone formation parameters were not significantly affected by ZOL 20 ,g/kg but were significantly reduced by ZOL 100,500 ,g/kg. Alendronate 200 ,g/kg was equivalent to ZOL 100 ,g/kg. ZOL produced dose-related improvements in bone strength parameters after ovariectomy. Alendronate 200 ,g/kg was of similar potency to ZOL 20 ,g/kg. Conclusions: The duration and magnitude of the bone-protecting effect of a single intravenous dose of ZOL in ovariectomized rats is dose dependent and lasts for up to 32 wk. Compared with alendronate, ZOL shows 10-fold higher potency in preventing bone loss. These data support the use of an annual intravenous ZOL dosing regimen for the treatment of osteoporosis. [source] Effect of Alendronate on the Age-Specific Incidence of Symptomatic Osteoporotic FracturesJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2005Marc C Hochberg MD Abstract Analyses of data from 3658 postmenopausal women with osteoporosis enrolled in the Fracture Intervention Trial showed that alendronate is effective in reducing the risk of symptomatic osteoporotic fractures across a spectrum of ages. Introduction: Most osteoporosis studies examine the relative risk of fracture based on the entire duration of treatment. Because older patients tend to be at higher risk for osteoporosis-related fractures, this analysis examined the effect of alendronate treatment on the relative risk of fracture in terms of the age that patients attained during the study. Materials and Methods: We studied 3658 postmenopausal women with osteoporosis 55-80 years of age at baseline enrolled in the Fracture Intervention Trial, a large randomized, double-blind, placebo-controlled study. Patients were treated with placebo or with alendronate at a daily dose of 5 mg for 2 years followed by 10 mg for an additional 1-2.5 years, and monitored for clinical fractures. Age, rather than study time, was the dynamic variable in our analysis. Results: The relative risk reductions for hip, clinical spine, and wrist fractures were constant across age groups, without evidence of a decline at older ages. Specifically, alendronate reduced the risk of clinical fracture by 53% at the hip (relative risk [RR] = 0.47; 95% CI = 0.27-0.81; p < 0.01), 45% at the spine (RR = 0.55; 95% CI = 0.37-0.83; p < 0.01), and 31% at the wrist (RR = 0.69; 95% CI = 0.50-0.98; p = 0.038). In addition, alendronate produced a significant risk reduction of 40% (RR = 0.60; 95% CI = 0.47-0.77; p < 0.01) for the composite event of clinical hip, spine, and wrist fractures. As a consequence of the constant relative risk model, the absolute risk reduction with alendronate treatment increased with age because of the age-related increase in fracture risk in the placebo group. The absolute risk reduction for the composite event (hip, spine, and wrist fractures together) for alendronate treatment versus placebo was 65, 80, 111, and 161 women with fractures per 10,000 PYR for the 55 to <65, 65 to <70, 70 to <75, and 75-85 year age groups, respectively. Conclusions: These data show that alendronate is effective in reducing the risk of symptomatic osteoporotic fractures across a spectrum of ages. The effectiveness is somewhat greater in patients with femoral neck T score , ,2.5 than in those with a T score , ,2.0. [source] Timing relationships between pegmatite emplacement, metamorphism and deformation during the intra-plate Alice Springs Orogeny, central AustraliaJOURNAL OF METAMORPHIC GEOLOGY, Issue 9 2008I. S. BUICK Abstract In the Harts Range (central Australia), the upper amphibolite facies to lower granulite facies, c. 480,460 Ma Harts Range Metamorphic Complex (HRMC), and the upper amphibolite facies, c. 340,320 Ma Entia Gneiss Complex are cut by numerous, generally peraluminous pegmatites and their deformed equivalents. The pegmatites have previously been interpreted as locally derived partial melts. However, SHRIMP U,Pb monazite and zircon dating of 29 pegmatites or their deformed equivalents, predominantly from the HRMC, reveal that they were emplaced episodically throughout almost the entire duration of the polyphase, c. 450,300 Ma intra-plate Alice Springs Orogeny. Episodes of pegmatite intrusion correlate with the age of major Alice Springs-age structures and with deposition of syn-orogenic sedimentary rocks in the adjacent Centralian Superbasin. Similar Alice Springs ages have not been obtained from anatectic country rocks in the HRMC, suggesting that the pegmatites were not locally derived. Instead, they are interpreted as highly fractionated granites, and imply that much larger parental Alice Springs-age granites exist at depth. The mechanism to allow repeated felsic magmatism in an intraplate setting, where all exposed rock types had a previous high-temperature history, is enigmatic. However, we suggest that episodic underthrusting and dehydration of unmetamorphosed Centralian Superbasin sedimentary rocks allowed crustal fertility to maintained over a c. 140 Ma interval during the intra-plate Alice Springs Orogeny. [source] Neuropeptide Y Counteracts the Anorectic and Weight Reducing Effects of Ciliary Neurotropic FactorJOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2000S. Pu Abstract Ciliary neurotrophic factor (CNTF), a cytokine of the interleukin-6 superfamily, has been shown to induce hypophagia and weight loss. Neuropeptide Y (NPY) and orexin are potent orexigenic signals in the hypothalamus. Anorexia, normally seen in response to infection, injury and inflammation, may result from diminished hypothalamic orexigenic signalling caused by persistently elevated cytokines, including CNTF. To test this hypothesis, we first examined the effects of chronic intracerebroventricular (i.c.v.) infusion of CNTF for 6,7 days on food intake and body weight as well as hypothalamic NPY and orexin gene expression in male rats. Subsequently, the effectiveness of NPY replacement to counteract the effects of CNTF by coinfusion of NPY and CNTF was evaluated. Chronic i.c.v. infusion of CNTF (2.5 µg/day) reduced body weight (14.3% vs control) at the end of 7 days. Food intake remained suppressed for 5 days postinfusion and subsequently gradually returned to the control range by day 7. Serum leptin concentrations in these rats were in the same range seen in control rats. Chronic i.c.v. infusion of higher doses of CNTF (5.0 µg/day) produced sustained anorexia and body weight loss (29% vs controls) through the entire duration of the experiment. This severe anorexia was accompanied by markedly suppressed serum leptin concentrations. Furthermore, CNTF infusion alone significantly reduced hypothalamic NPY gene expression (P < 0.05) without affecting orexin gene expression. As expected, in fusion of NPY alone (18 µg/day) augmented food intake (191.6% over the initial control, P < 0.05) and produced a 25.1% weight gain in conjunction with a 10-fold increase in serum leptin concentrations at the end of the 7-day period. Interestingly, coinfusion of this regimen of NPY with the highly effective anorectic and body reducing effects of CNTF (5.0 µg/day) not only prevented the CNTF-induced anorexia and weight loss, but also normalized serum leptin concentrations and hypothalamic NPY gene expression. These results demonstrate that chronic central infusion to produce a persistent elevation of the cytokine at pathophysiological levels (a situation that may normally manifest during infection, injury and inflammation) produced severe anorexia and weight loss in conjunction with reduction in both serum leptin concentrations and hypothalamic NPY gene expression. Reinstatement of hypothalamic NPY signalling by coinfusion of NPY counteracted these CNTF-induced responses. [source] Unilateral groin surgery in children: will the addition of an ultrasound-guided ilioinguinal nerve block enhance the duration of analgesia of a single-shot caudal block?PEDIATRIC ANESTHESIA, Issue 9 2009NARASIMHAN JAGANNATHAN MD Summary Background:, Inguinal hernia repair, hydrocelectomy, and orchidopexy are commonly performed surgical procedures in children. Postoperative pain control is usually provided with a single-shot caudal block. Blockade of the ilioinguinal nerve may lead to additional analgesia. The aim of this double-blind, randomized controlled trial was to evaluate the efficacy of an adjuvant blockade of the ilioinguinal nerve using ultrasound (US) guidance at the end of the procedure with local anesthetic vs normal saline and to explore the potential for prolongation of analgesia with decreased need for postoperative pain medication. Methods:, Fifty children ages 1,6 years scheduled for unilateral inguinal hernia repair, hydrocelectomy, orchidopexy, or orchiectomy were prospectively randomized into one of two groups: Group S that received an US-guided ilioinguinal nerve block with 0.1 ml·kg,1 of preservative-free normal saline and Group B that received an US-guided nerve block with 0.1 ml·kg,1 of 0.25% bupivacaine with 1 : 200 000 epinephrine at the conclusion of the surgery. After induction of anesthesia but prior to surgical incision, all patients received caudal anesthesia with 0.7 ml·kg,1 of 0.125% bupivacaine with 1 : 200 000 epinephrine. Patients were observed by a blinded observer for (i) pain scores using the Children and Infants Postoperative Pain Scale, (ii) need for rescue medication in the PACU, (iii) need for oral pain medications given by the parents at home. Results:, Forty-eight patients, consisting of 46 males and two females, with a mean age of 3.98 (sd ± 1.88) were enrolled in the study. Two patients were excluded from the study because of study protocol violation and/or alteration in surgical procedure. The average pain scores reported for the entire duration spent in the recovery room for the caudal and caudal/ilioinguinal block groups were 1.92 (sd ± 1.59) and 1.18 (sd ± 1.31), respectively. The average pain score difference was 0.72 (sd ± 0.58) and was statistically significant (P < 0.05). In addition, when examined by procedure type, it was found that the difference in the average pain scores between the caudal and caudal/ilioinguinal block groups was statistically significant for the inguinal hernia repair patients (P < 0.05) but not for the other groin surgery patients (P = 0.13). For all groin surgery patients, six of the 23 patients in the caudal group and eight of the 25 patients in the caudal/ilioinguinal block group required pain rescue medications throughout their entire hospital stay or at home (P = 0.76). Overall, the caudal group received an average of 0.54 (sd ± 1.14) pain rescue medication doses, while the caudal/ilioinguinal block group received an average of 0.77 (sd ± 1.70) pain rescue medication doses; this was, however, not statistically significant (P = 0.58). Conclusions:, The addition of an US-guided ilioinguinal nerve block to a single-shot caudal block decreases the severity of pain experienced by pediatric groin surgery patients. The decrease in pain scores were particularly pronounced in inguinal hernia repair patients. [source] Consequences to Hearing During the Conservative Management of Vestibular Schwannomas,THE LARYNGOSCOPE, Issue 2 2000FRCS(ORL), Rory M. Walsh MA Abstract Objective: To estimate the risk of loss of serviceable hearing during the conservative management of vestibular schwannomas. Study Design: Retrospective case review. Methods: Twenty-five patients with a radiological diagnosis of unilateral vestibular schwannoma were managed conservatively for a mean duration of 43.8 months (range, 12,194 mo). The pure-tone average (PTA) (0.5, 1, 2, and 3 kHz) and speech discrimination scores (SDS) were measured at regular intervals throughout the entire duration of follow-up. Serviceable hearing was defined using two criteria: 70% SDS/30 dB PTA (the 70/30 rule) and 50% SDS/50 dB PTA (the 50/50 rule). The size and growth rate of tumors were determined according to the American Academy of Otolaryngology,Head and Neck Surgery guidelines (1995). Intervention was recommended if there was evidence of continuous or rapid radiological tumor growth, and/or increasing symptoms or signs suggestive of tumor growth. Results: The risk of loss of serviceable hearing for the total group was 43% using the 70/30 rule and 42% using the 50/50 rule. Tumor growth was considered significant (> 1 mm) in 8 tumors (32%) and nonsignificant in 17 (68%). The risk of loss of serviceable hearing for the tumor-growth group was 67% using the 70/30 rule and 80% using the 50/50 rule. In contrast, the risk of loss of serviceable hearing for the no tumor,growth group was 25% using the 70/30 rule and 14% using the 50/50 rule. No audiological factors predictive of tumor growth were identified. Conclusions: There is a significant risk of loss of serviceable hearing during the conservative management of vestibular schwannomas. This risk appears to be greater in tumors that demonstrate significant growth. [source] An evaluation of DVAqua®, a fully-fermented yeast culture, during long-term hatchery rearing of McConaughy strain rainbow troutAQUACULTURE NUTRITION, Issue 3 2010M.E. BARNES Abstract The addition of a proprietary, fully-fermented yeast Saccahromyces cerevisiae culture supplement (DVAqua®, Diamond V Mills, Cedar Rapids, IA, USA) was evaluated during long-term feeding of McConaughy strain rainbow trout Oncorhynchus mykiss. Beginning at initial feeding and continuing for 408 days of hatchery rearing, the trout received either a commercially-manufactured feed or the same feed containing 0.125 g kg,1 DVAqua. This study was conducted at a production level as part of normal (real-world) hatchery operations, with the fish periodically inventoried and moved into different rearing units. Although no rearing-tank replication occurred during the first 54 days of feeding, multiple tanks and raceways were used thereafter. Fish in rearing units receiving DVAqua supplementation exhibited less mortality, particularly during the earlier rearing stages. During the final 177 days of rearing in six raceways, DVAqua-fed McConaughy strain trout were significantly larger and had a significantly improved feed conversion ratio. The overall feed conversion ratio for the entire duration of the study was 1.17 in the fish receiving DVAqua supplementation compared to 1.21 in the control group. Despite the limitations of this study, the use of DVAqua is recommended for McConaughy strain rainbow trout and other less-domesticated, more difficult-to-rear salmonids. [source] | |||||||||||||