bluuebunny/crossref_metadata_2025 huggingface dataset:
Apigenin (4‘,5,7-trihydroxyflavone) regulates hyperglycaemia, thyroid dysfunction and lipid peroxidation in alloxan-induced diabetic mice
Authors: Panda Sunanda , Kar Anand
Published: October 2007

The potential of apigenin (4′,5,7-trihydroxyflavone) in regulating hyperglycaemia, thyroid dysfunction and lipid peroxidation (LPO) has been revealed. While in alloxan-treated diabetic animals, a significant decrease in the concentrations of serum insulin, thyroxine (T4) and triiodothyronine (T3), with a parallel increase in serum glucose and hepatic glucose-6-phospatase (G-6-Pase) activity, was observed, administration of 0.78 mg kg−1 of apigenin for 10 consecutive days increased the levels of serum insulin and thyroid hormones with a parallel decrease in glucose concentration and hepatic G-6-Pase activity. Alloxan-induced elevation in serum cholesterol was also reduced by the compound. With respect to LPO, while in alloxan-treated animals an increase in hepatic LPO and a decrease in the activity of cellular antioxidants, such as catalase (CAT) and superoxide dismutase (SOD), and in glutathione (GSH) content was observed, administration of apigenin to alloxan-treated mice reversed all these changes, suggesting its hepatoprotective potential. Similar effects of apigenin were also observed in most of the parameters in normoglycaemic animals. It appears that apigenin has a potential to regulate diabetes mellitus, as well as disease-induced thyroid dysfunction and lipid peroxidation.
Gastroprotective properties of Myristica malabarica against indometacin-induced stomach ulceration: a mechanistic exploration
Authors: Banerjee Debashish , Maity Biswanath , Bauri Ajay K , Bandyopadhyay Sandip K , Chattopadhyay Subrata
Published: October 2007

The healing activity of the methanol extract of the spice rampatri, Myristica malabarica, (RM) and omeprazole against indometacin-induced stomach ulceration has been studied in a mouse model. Treatment with RM (40 mg kg−1 per day) and omeprazole (3 mg kg−1 per day) for 3 days could effectively heal the stomach ulceration, as revealed from the ulcer indices and histopathological studies. Compared with the ulcerated group, treatment with RM and omeprazole for 3 days reduced the macroscopic damage score by approximately 72% and 76%, respectively (P < 0.001), establishing the efficacy of RM. The extent of ulcer healing offered by 3 days' treatment with RM or omeprazole was better than that observed with natural recovery over 5 and 7 days (P < 0.05). The healing capacities of RM and omeprazole could be attributed to their antioxidant activity as well as the ability to enhance the mucin content of the gastric tissues. Both drugs reduced lipid peroxidation (by 42–44%) and protein carbonyl content (by 34%), and augmented non-protein thiol levels beyond normal values. Furthermore, RM improved the mucin level beyond the normal value, while omeprazole restored it to near normalcy.
Scutellaria baicalensis and a constituent flavonoid, baicalein, attenuate ritonavir-induced gastrointestinal side-effects
Authors: Mehendale Sangeeta , Aung Han , Wang Chong-Zhi , Tong Robin , Foo Adela , Xie Jing-Tian , Yuan Chun-Su
Published: October 2007

Ritonavir, a protease inhibitor drug, is commonly used in AIDS therapy. As with other chemotherapeutic drugs that cause gastrointestinal adverse effects, ritonavir treatment is associated with significant nausea and vomiting. This study investigated whether Scutellaria baicalensis, and its active flavonoid constituent, baicalein, attenuate the gastrointestinal effects of ritonavir. The effects of herb administration were evaluated in ritonavir-treated rats using a rat pica model, which simulates nausea and vomiting in humans. The effects of herb administration on gastric emptying in rats were also measured. Ritonavir treatment resulted in increased kaolin intake or severe pica, the intensity of which was reduced significantly with S. baicalensis administration (1 mg kg−1; P < 0.05). High-performance liquid chromatography analysis of S. baicalensis showed the presence of an extremely potent flavonoid constituent, baicalein. The study aimed to determine if baicalein contributed to the anti-pica effect of the extract. It was observed that baicalein dose-dependently decreased pica in ritonavir-treated rats (P < 0.001). In addition to inducing pica, ritonavir also significantly delayed gastric emptying, which could contribute to ritonavir-induced gastrointestinal dysfunction. When S. baicalensis extract was administered to ritonavir-treated rats the delayed gastric emptying was significantly attenuated (P < 0.05). The results suggest that S. baicalensis and the constituent baicalein reduce the gastrointestinal dysfunction caused by ritonavir. It is concluded that S. baicalensis may potentially have a role to play in reducing drug-induced adverse effects.
Antinociceptive action of limonexic acid obtained fromRaulinoa echinata
Authors: Biavatti Maique W , Westerlon Rosângela , Burger Cristiani , Mora Ticiana Camila , De Souza Márcia Maria
Published: October 2007

The antinociceptive effect of the limonexic acid isolate of Raulinoa echinata Cowan in four models of pain in mice is described. When evaluated against acetic acid-induced abdominal constrictions, limonexic acid (10, 30 and 60 mg kg−1, i.p.) produced dose-related inhibition of the number of constrictions, with a mean ID50 value of 43 (2.3–79) μmol kg−1, and was more potent than some standard drugs. In the formalin test, limonexic acid inhibited both the first and second phases of formalin-induced pain. Furthermore, the effect was more pronounced in the second phase, with a mean ID50 value of 13.66 (9.35–19.61) μmol kg−1, and had a pharmacological profile that was similar to standard drugs such as acetaminophen and acetyl salicylic acid. Limonexic acid also produced dose-related inhibition of glutamate- and capsaicin-induced pain, with mean ID50 values of 11.67 (8.51–16.0) μmol kg−1 and 47.17 (36.51–60.93) μmol kg−1, respectively. The mechanism of action is not completely understood, but seems to involve direct interaction with the GABAergic and nitroxidergic pathways.
Lrp6 is required for convergent extension duringXenopusgastrulation
Authors: Tahinci Emilios , Thorne Curtis A. , Franklin Jeffrey L. , Salic Adrian , Christian Kelly M. , Lee Laura A. , Coffey Robert J. , Lee Ethan
Published: October 2007

Wnt signaling regulates β-catenin-mediated gene transcription and planar cell polarity (PCP). The Wnt co-receptor, Lrp6, is required for signaling along the β-catenin arm. We show that Lrp6 downregulation (by morpholino injection) or overexpression in Xenopus embryos disrupts convergent extension, a hallmark feature of Wnt/PCP components. In embryos with decreased Lrp6 levels, cells of the dorsal marginal zone (DMZ), which undergoes extensive cellular rearrangements during gastrulation, exhibit decreased length:width ratios, decreased migration, and increased numbers of transient cytoplasmic protrusions. We show that Lrp6 opposes Wnt11 activity and localizes to the posterior edge of migrating DMZ cells and that Lrp6 downregulation enhances cortical and nuclear localization of Dsh and phospho-JNK, respectively. Taken together, these data suggest that Lrp6 inhibits Wnt/PCP signaling. Finally, we identify the region of the Lrp6 protein with Wnt/PCP activity to a stretch of 36 amino acids, distinct from regions required for Wnt/β-catenin signaling. We propose a model in which Lrp6 plays a critical role in the switch from Wnt/PCP to Wnt/β-catenin signaling.
Pair housing of rabbits reduces variances in growth rates and serum alkaline phosphatase levels
Authors: Nevalainen T O , Nevalainen J I , Guhad F A , Lang C M
Published: October 2007

New Council of Europe regulations mandate housing of two rabbits in the same cage space currently used to house one, provided the animals are socially compatible. This study was designed to assess changes in growth and selected serum chemistry parameters due to pair housing or single housing of rabbits. Six sets of four female siblings of Crl:KBL(NZW)BR rabbits were used. The animals were seven weeks old on arrival. Two siblings of each set were allocated to pair housing, two to single housing. The animals were housed in stainless steel cages (120 cm × 60 cm × 60 cm) with a perforated floor, including a shelf (60 cm × 30 cm) at 30 cm height from the floor. The rabbits were provided with an aspen cube (5 cm × 5 cm × 5 cm), one item per animal. The rabbits were weighed and blood samples were taken from the auricular central artery at four different times during the study. Blood sera were assayed for a set of routinely assayed clinical chemistry parameters: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (APHOS), blood urea nitrogen (BUN), cholesterol (CHOL) and protein (PROT). Mean and variance profiles over the study period were statistically analysed by multivariate analysis of variance. No differences in mean profiles were detected; however, weight ( P = 0.0002) and APHOS ( P = 0.017) variances were significantly lower in pair-housed animals. The reduction in variance on growth and APHOS attributable to pair housing appears to be rather large. During the 21-week study, occasional fighting was seen between the pair-housed rabbits. After sexual maturity, further major fighting bouts resulted in significant trauma that necessitated the cessation of the study. In conclusion, pair housing appears to have a decreasing effect on growth and APHOS variance, but antisocial behaviour such as fighting remains a serious problem.
Identification of bacterial strains by laboratories participating in the Deutsches Krebsforschungszentrum quality assurance programme
Authors: Boot R , Reubsaet F A G
Published: October 2007

The quality assurance programme (QAP) of the Deutsches Krebsforschungszentrum (DKFZ) is a proficiency testing system developed to service the laboratory animal discipline. QAP comprises the quarterly distribution of two bacterial strains originating from various species of animals for identification to the species level and antibiotic susceptibility testing. We compared identification results reported by QAP participants over the years 1996–2004 with those obtained by the Dutch Bacterial Diagnostics reference laboratory on 68 samples comprising 71 bacterial strains and a fungus. Significant differences were found in the frequency of reported and correct identifications when bacteria were assigned to different groups based on morphology by Gram stain and on origin (animal versus environmental, rodent and rabbit versus other animal species, pathogen versus non-pathogens). Rodent and rabbit pathogens yielded 73% correct identifications, and with all bacterial strains only 60% of the identifications were correct. We assume that most QAP participants were from laboratory animal diagnostic laboratories. If this is true, the capabilities of laboratories in the laboratory animal discipline to correctly identify bacterial species are well below what are considered acceptable limits for human diagnostic laboratories. The distribution of cultured bacteria circumvents the most difficult step in the microbiological monitoring of animals, namely primary culture from clinical samples. We propose to set up a QAP that comprises the distribution of specimens mimicking clinical samples normally submitted to laboratory animal diagnostic laboratories.
Pituitary–adrenocortical axis, serum serotonin and biochemical response after halothane or isoflurane anaesthesia in rabbits
Authors: Gil Alfredo González , Silván Gema , Illera Juan C
Published: October 2007

To document the changes in serum serotonin, adrenocorticotrophic hormone (ACTH), corticosterone levels and select biochemical parameters in response to inhalant anaesthesia, 20 New Zealand White (NZW) rabbits were assigned to two treatment groups: halothane and isoflurane. Induction of anaesthesia was achieved using a face mask (3.5% halothane and 4.5% isoflurane in oxygen) followed by endotracheal intubation and maintenance of anaesthesia for 30 min (1.5% halothane and 2.5% isoflurane in oxygen). Blood samples were obtained before anaesthetic induction, and at 1, 10, 30, 60, 120 min and 24, 48 and 72 h after endotracheal intubation. Serum serotonin and corticosterone levels were measured by competitive enzyme immunoassay, ACTH by radioimmunoassay. Serum glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN) and creatinine levels were measured using an automated analyser. Significant increases in serum ACTH and corticosterone levels occurred after halothane administration while serum serotonin levels did not change. An increase in serum corticosterone and serotonin levels occurred in the isoflurane group but no changes in ACTH concentrations were detected. Administration of halothane significantly increased serum glucose, ALT, AST, BUN and creatinine levels. After isoflurane administration, there was a significant increase in serum glucose, AST, BUN and creatinine levels. Based on these results, halothane stimulates the hypothalamic–pituitary–adrenal axis to a greater extent than isoflurane, but isoflurane increases serum serotonin levels. Both anaesthetic agents alter select biochemical parameters. These results should be taken into account when blood samples are evaluated in treated isoflurane or halothane anaesthetized rabbits.
A surgical technique for catheterization of the sagittal sinus in pigs
Authors: Schütze Michael , Janda Matthias , Bajorat Jörn , Piek Juergen , Nöldge-Schomburg Gabriele F E , Hofmockel Rainer
Published: October 2007

The purpose of our study was to describe an efficient, reliable and inexpensive surgical method for cerebral venous blood gas sampling in acutely instrumented pigs in a research setting. Parameters from the blood samples are used to monitor brain perfusion and oxygenation in different animal models. To the authors' knowledge, this is the first detailed description of an accurate surgical technique for catheterization of the sagittal sinus in pigs.
Impact of 'living apart together' on postoperative recovery of mice compared with social and individual housing
Authors: Van Loo Pascalle L P , Kuin Nynke , Sommer René , Avsaroglu Harut , Pham Therese , Baumans Vera
Published: October 2007

Social housing is the optimal way of housing female laboratory mice. However, individual housing may be required in experimental designs, for example after surgery. We therefore investigated whether housing two female mice in a cage, separated by a grid partition ('living apart together', LAT), counters the adverse effects of individual housing on postoperative recovery. Ten individually housed (IND) mice, nine socially housed (SOC) mice and nine mice, housed LAT, were surgically implanted with a telemetry transmitter. From one week prior to surgery until three weeks thereafter, several physiological and behavioural parameters were measured in the mice subjected to surgery. The telemetry transmitter measured heart rate (HR), body temperature and activity continuously. Body weight, food and water intake were scored regularly, as were wound healing, ease of handling, nest building and behaviour. Results indicated that SOC mice appear to be less affected by abdominal surgery than IND mice, as indicated by HR and behaviour. LAT, however, did not appear to be beneficiary to the mice. Increased HR levels and differences in behaviour as compared with both SOC and IND animals indicate that LAT may even be the most stressful of the three housing conditions. We therefore conclude that mice benefit most from social housing after surgery. If, however, social housing is not possible, individual housing appears to be a better option than separating mice by a grid partition.
Measurements of blood pressure and electrocardiogram in conscious freely moving guineapigs: a model for screening QT interval prolongation effects
Authors: Hess P , Rey M , Wanner D , Steiner B , Clozel M
Published: October 2007

The pro-arrhythmic risk inherent to a new drug must be assessed at an early preclinical stage. Telemetry system implantation is a method widely used in vivo in various species. The present study was designed to assess whether conscious freely moving guineapigs can be used to predict QT prolongation in vivo. The guineapig has three advantages over the dog and the primate. First, it has specific ion channels similar to man; second, a smaller amount of test article is required for the investigation and third, its housing is less expensive. Under sterile conditions and isoflurane anaesthesia, telemetry transmitters were implanted intraperitoneally in male Dunkin Hartley guineapigs. Blood pressure, heart rate and electrocardiographic intervals were measured from two days up to eight months. Chronic implantation of the telemetry device did not lead to anatomic or macroscopic alterations in the abdominal cavity and no inflammation of the peritoneum or infection was observed. Four reference compounds were used: three positive (sotalol, terfenadine and dofetilide) and one negative reference (enalapril). Single oral administration of all three positive references dose-dependently induced bradycardia and QT corrected (QTc) prolongation. In contrast, neither enalapril nor its vehicle prolonged the QTc. These results demonstrate that the guineapig is both a suitable model and a good alternative to dogs or primates to assess the potential of compounds for QT interval prolongation in the early stages of drug development.
Clostridium difficile and the first objective
Authors: Morris Vicky
Published: October 2007

Healthcare-associated infection (HAI) is a hot topic. In its investigation into the two outbreaks of Clostridium difficile at Stoke Mandeville in 2005, the Healthcare Commission was highly critical of the way the Trust had handled the situation and, in its wake, senior managers of the Trust's Board were replaced. Since then the Hygiene Code and various other initiatives have been introduced. There has been widespread media coverage and understandable interest in and concern about the issue. We have seen the first decided case on the applicability of the COSHH regulations to claims arising from infection in a healthcare setting and recent publication of the draft findings of the Health & Safety Executive report into Stoke Mandeville. Added to that is a lively debate as to the applicability of Fairchild to claims for HAI. This article looks at some of the practical and legal issues around claims for C. difficile behind the politics and media frenzy.
Truth-telling, autonomy and paternalism in healthcare: a commentary on the case of Gary Dimmock v East Sussex NHS Trust
Authors: Stirrat Gordon M
Published: October 2007

Multiple sclerosis (MS) presents with many different signs and symptoms, has a multitude of differential diagnoses and there is no specific test for it. In many instances, even with all available investigations, it is not possible to reach a definite diagnosis in the early stages. It is strongly recommended that the person should be informed of a potential diagnosis of MS as soon as it is considered reasonably likely and that this should occur before undertaking further investigations. People with MS should also play an active part in making informed decisions about all aspects of their care by being given relevant and accurate information on each choice and decision. The case is considered in light of the above with particular reference to the linked ethical issues of truth-telling, trust, patient autonomy and paternalism.
Nephrology for lawyers
Authors: Mansell Martin A
Published: October 2007

This article is based on the Nephrology chapter in Medical Mistakes Key Medical Issues in Clinical Negligence Cases published by Claerhout Publishing in 2007. It provides an overview of renal medicine, how renal problems are detected, common diseases of the kidneys and treatment.
Case: Diagnosis of multiple sclerosis withheld for eight years from the patient Gary Dimmock v East Sussex NHS Trust
Authors: Nairne Katie
Published: October 2007

A case is presented in which the diagnosis of multiple sclerosis (MS) was withheld for eight years from the patient. Apparently, the treating doctors decided that it was best for the patient not to know that he probably had MS. Court proceedings were commenced after the patient became aware of the diagnosis and the case was settled for £10,000.
Managing the clinical and medicolegal risks of obesity
Authors: Chappell Julie
Published: October 2007

Obesity is a major public health problem and could soon become a major medicolegal issue as well if appropriate risk management is not undertaken. Apart from the clinical complications of obesity, problems could arise from the use of inappropriate equipment. Insufficiently strong equipment used to move/transport/treat an obese patient could break or fail. Staff who manually handle obese patients without proper equipment and training could suffer back injuries. These types of claims should be preventable with sufficient investment in equipment and training. Unless the problem is addressed now, there could be an increase in claims. These will include clinical negligence claims brought on patients' behalf for injuries due to handling difficulties, equipment failure, problems with calculation of drug doses and failure of diagnosis. There will also be personal injury claims associated with manual handling of obese patients brought by the medical staff responsible for their care.
Research and Development Project Valuation and Licensing Negotiations at Phytopharm plc
Authors: Crama Pascale , Reyck Bert De , Degraeve Zeger , Chong Wang
Published: October 2007

We describe a research and development project-valuation model developed for Phytopharm plc, a pharmaceutical development and functional food company based in Cambridgeshire, United Kingdom. Phytopharm uses the model to value the projects in its research and development portfolio, and in licensing negotiations with potential product development and marketing partners. We include different valuation methods, including net present value, decision analysis, and Monte Carlo simulation. We also consider the technological risks of product development, as well as the uncertainty of commercial success. In addition to determining a value for a product in development, the model proposes appropriate licensing contract structures. A typical licensing contract specifies milestone payments and royalties to be paid by the licensee to the licensor. The contract structures adhere to an agreed-upon equitable split of the project value between the two parties. The model also generates critical information during the negotiation meetings, including break-even analyses, trade-offs, and bargaining zones. Phytopharm is currently deploying the model for use with its entire project portfolio.
Solving Real-Life Railroad Blocking Problems
Authors: Ahuja Ravindra K. , Jha Krishna C. , Liu Jian
Published: October 2007

Each major US railroad ships millions of cars over its network annually. To reduce the intermediate handlings of shipments as they travel over the railroad network, a set of shipments is classified (or grouped together) at a railroad yard to create a block. The railroad blocking problem is to identify this classification plan for all shipments at all yards in the network to minimize the total shipment cost, i.e., to create a blocking plan. The railroad blocking problem is a very large-scale, multicommodity, flow-network-design and routing problem with billions of decision variables. Its size and mathematical difficulty preclude solving it using any commercial software package. We developed an algorithm using an emerging technique known as very large-scale neighborhood (VLSN) search that is able to solve the problem to near optimality using one to two hours of computer time on a standard workstation computer. This algorithm can also handle a variety of practical and business constraints that are necessary for implementing a solution. When we applied this algorithm to the data that several railroads provided us, the computational results were excellent. Three Class I railroad companies (a Class I railroad, as defined by the Association of American Railroads, has an operating revenue exceeding $319.3 million) in the United States—CSX Transportation, Norfolk Southern Corporation, and Burlington Northern and Santa Fe Railway—used it in developing their operating plans. Two US Class I railroads have also licensed it for regular use in developing their operating plans, and other railroads are showing considerable interest. We expect this algorithm to become an industry standard for freight railroads worldwide. In this paper, we outline our algorithm, show the computational results we received using real data, and describe areas for future research.
Optimal Control of an Inventory with Simultaneous Obsolescence
Authors: Emsermann Markus , Simon Burton
Published: October 2007

We consider the problem of determining the optimal ordering and reordering policy for an inventory in which the entire stock will simultaneously become obsolete at some (typically random) future time. Many manufacturing, publishing, distribution, and high-tech businesses face the challenge of maintaining inventories that do not age in the conventional sense; instead, they suddenly become obsolete and lose most or all of their value. These circumstances render traditional inventory analysis unsuitable for balancing reordering costs with the costs of overstocking. We study a continuous-review and stochastic-demand obsolescence inventory model, and calculate its optimal control policy. We gear our solution technique to problems that involve large inventories and small holding costs.
Transport of carnitine and acetylcarnitine by carnitine/organic cation transporter (OCTN) 2 and OCTN3 into epididymal spermatozoa
Authors: Kobayashi Daisuke , Tamai Ikumi , Sai Yoshimichi , Yoshida Kazuhiro , Wakayama Tomohiko , Kido Yasuto , Nezu Jun-ichi , Iseki Shoichi , Tsuji Akira
Published: October 2007

Carnitine and acetylcarnitine are important for the acquisition of motility and maturation of spermatozoa in the epididymis. In this study, we examined the involvement of carnitine/organic cation transporter (OCTN) in carnitine and acetylcarnitine transport in epididymal spermatozoa of mice. Uptake of both compounds by epididymal spermatozoa was time-dependent and partially Na+-dependent. Kinetic analyses revealed the presence of a high-affinity transport system in the spermatozoa, with Km values of 23.6 and 6.57 μM for carnitine and acetylcarnitine respectively in the presence of Na+. Expression of OCTN2 and OCTN3 in epididymal spermatozoa was confirmed by immunofluorescence analysis. The involvement of these two transporters in carnitine and acetylcarnitine transport was supported by a selective inhibition study. We conclude that both Na+-dependent and -independent carnitine transporters, OCTN2 and OCTN3, mediate the supply of carnitine and acetylcarnitine to epididymal spermatozoa in mice.
Ovarian follicular cells have innate immune capabilities that modulate their endocrine function
Authors: Herath Shan , Williams Erin J , Lilly Sonia T , Gilbert Robert O , Dobson Hilary , Bryant Clare E , Sheldon I Martin
Published: October 2007

Oestrogens are pivotal in ovarian follicular growth, development and function, with fundamental roles in steroidogenesis, nurturing the oocyte and ovulation. Infections with bacteria such as Escherichia coli cause infertility in mammals at least in part by perturbing ovarian follicle function, characterised by suppression of oestradiol production. Ovarian follicle granulosa cells produce oestradiol by aromatisation of androstenedione from the theca cells, under the regulation of gonadotrophins such as FSH. Many of the effects of E. coli are mediated by its surface molecule lipopolysaccharide (LPS) binding to the Toll-like receptor-4 (TLR4), CD14, MD-2 receptor complex on immune cells, but immune cells are not present inside ovarian follicles. The present study tested the hypothesis that granulosa cells express the TLR4 complex and LPS directly perturbs their secretion of oestradiol. Granulosa cells from recruited or dominant follicles are exposed to LPS in vivo and when they were cultured in the absence of immune cell contamination in vitro they produced less oestradiol when challenged with LPS, although theca cell androstenedione production was unchanged. The suppression of oestradiol production by LPS was associated with down-regulation of transcripts for aromatase in granulosa cells, and did not affect cell survival. Furthermore, these cells expressed TLR4, CD14 and MD-2 transcripts throughout the key stages of follicle growth and development. It appears that granulosa cells have an immune capability to detect bacterial infection, which perturbs follicle steroidogenesis, and this is a likely mechanism by which ovarian follicle growth and function is perturbed during bacterial infection.
Release of phospholipase C ζand [Ca2+]i oscillation-inducing activity during mammalian fertilization
Authors: Yoon Sook-Young , Fissore Rafael A
Published: October 2007

During fertilization of mammalian eggs a factor from the sperm, the sperm factor (SF), is released into the ooplasm and induces persistent [Ca2+]i oscillations that are required for egg activation and embryo development. A sperm-specific phospholipase C (PLC), PLCz, is thought to be the SF. Here, we investigated whether the SF activity and PLCζare simultaneously and completely released into the ooplasm soon after sperm entry. To accomplish this, we enucleated sperm heads within 90 min of intracytoplasmic sperm injection (ICSI) and monitored the persistence of the [Ca2+]i oscillations in eggs in which the sperm had been withdrawn. We also stained the enucleatedsperm heads to ascertain the presence/absence of PLCζ. Our results show that by 90 min all the SF activity had been released from the sperm, as fertilized enucleated eggs oscillated as fertilized controls, even in cases in which oscillations were prolonged by arresting eggs at metaphase. In addition, we found that the released SF activity became associated with the pronucleus (PN), as induction of PN envelope breakdown evoked comparable [Ca2+]i responses in enucleated and non-manipulated zygotes. Lastly, we found that PLCzlocalized to the equatorial area of bull sperm and to the post-acrosomal region of mouse sperm and that by 90 min after ICSI all the sperm’s PLCζimmunoreactivity was lost in both species. Altogether, our findings show that during fertilization the SF activity and PLCζimmunoreactivity are simultaneously released from the sperm, suggesting that PLCζmay be the only [Ca2+]i oscillation-inducing factor of mammalian sperm.
Effect of direct ovarian injection of vascular endothelial growth factor gene fragments on follicular development in immature female rats
Authors: Shimizu Takashi , Iijima Koji , Miyabayashi Kanako , Ogawa Yoshinori , Miyazaki Hitoshi , Sasada Hiroshi , Sato Eimei
Published: October 2007

Vascular endothelial growth factor (VEGF) expression in granulosa cells is associated with the thecal vasculature growth during ovarian follicular development. We hypothesized that injection of VEGF gene fragments directly into the rat ovary would induce production of a large number of ovulatory follicles and that these follicles would ovulate. To test this hypothesis, we treated immature female rats with combinations of hormones and VEGF gene fragments. The animals were divided into two groups: one group received solution containing transfection reagents as a control (n = 5), while the other group received direct ovarian injection of VEGF gene fragments at 19 (n = 5), 21 (n = 5), 23 (n = 5), or 25 (n = 5) days after birth followed by i.p. administration of 20 IU equine chorionic gonadotropin (eCG) at the age of 26 days. Forty-eight hours after eCG injection, animals were given 20 IU human chorionic gonadotropin (hCG) i.p. and then the oocytes in both groups were counted. The maximum number of ovulated oocytes was obtained when the VEGF gene fragments were injected into the rat ovary at 21 days after birth. Histological examination revealed that the injection of VEGF gene fragments markedly increased the vascular density around the preovulatory follicles and also the number of these follicles. Our data provide the first reported evidence that most ovulatory follicles generated by injection of VEGF gene fragments are able to ovulate upon hCG treatment. These results demonstrate that injection of VEGF gene fragments directly into the ovary stimulates the development of antral follicles by inducing the formation of thecal vasculature in immature female rats.
Prostaglandins and the initiation of blastocyst implantation and decidualization
Authors: Kennedy Thomas G , Gillio-Meina Carolina , Phang Sen Han
Published: October 2007

The process of blastocyst implantation in mammals is remarkably variable, especially in the extent of trophoblast invasion of the endometrium. In most species studied, the earliest macroscopically identifiable sign of blastocyst implantation is an increase in endometrial vascular permeability in areas adjacent to the blastocysts. This is followed in species with invasive implantation by decidualization, again localized to areas adjacent to the blastocysts. In some species, the application of a stimulus to the endometrium can result in increased endometrial vascular permeability and decidualization. Based initially on studies utilizing inhibitors of prostaglandin (PG) synthesis and more recently on studies using the techniques of transgenics, considerable evidence has accumulated indicating that PGs have an important role in the early events of implantation and artificially induced decidualization. However, which PGs are involved remains controversial. There may be differences between species, and different PGs may be involved at different times.
Acetaminophen Usage Patterns and Concentrations of Glutathione and γ‐Glutamyl Transferase in Alcoholic Subjects
Authors: Seifert Charles F , Anderson Douglas C.
Published: October 2007

Study Objectives. To determine if subjects with chronic alcoholism are predisposed to acetaminophen‐induced hepatotoxicity, and to determine the contributing factors.

Design. Prospective cohort study.

Setting. Community‐based crisis intervention center.

Subjects. One hundred eighty‐eight subjects who answered “yes” to at least one of the four questions on the CAGE (Cut down‐Annoyed‐Guilty‐Eye‐opener) questionnaire for identifying alcoholism, and 10 healthy volunteers (controls).

Intervention. A history, physical examination, urine toxicologic analysis, ethanol and drug therapy history, and venous blood samples were collected on all subjects.

Measurements and Main Results. Venous blood was analyzed for a liver profile, prothrombin time, and total and oxidized glutathione concentrations. A significantly higher proportion of daily drinkers were regular daily users (29.2% [45/154] vs 11.8% [4/34], p=0.0497) as well as abusers (35.7% [55/154] vs 14.7% [5/34], p=0.0237) of acetaminophen compared with nondaily drinkers. Alcoholic subjects with elevated γ‐glutamyl transferase (GGT ≥ 51 U/L) levels had significantly lower median plasma glutathione concentrations (2.33 μmol/L, 95% confidence interval [CI] 1.74‐2.69 μmol/L) compared with those of alcoholic subjects with normal GGT concentrations (5.97 μmol/L, 95% CI 4.39‐7.03 μmol/L, p<0.0001) and healthy volunteers (6.59 μmol/L, 95% CI 4.79‐9.65 μmol/L, p=0.0002). A significant inverse correlation was also noted between the GGT concentration and the plasma total glutathione concentration (r = −0.62, p<0.0001). None of the 188 subjects met all preset criteria for hepatotoxicity.

Conclusions. Daily drinkers were more than twice as likely as nondaily drinkers to be regular daily acetaminophen users and abusers. Alcoholic subjects with elevated GGT concentrations had significantly lower plasma total glutathione concentrations, and plasma total glutathione concentrations inversely correlated with GGT concentrations. Elevated GGT concentrations may be a clinical marker of depleted glutathione in alcoholic subjects. Acetaminophen‐induced hepatotoxicity appears to be uncommon in alcoholic subjects, despite the 31.9% (60/188 patients) who took doses that are potentially hepatotoxic.
Loss of Genomic Imprinting in Mouse Parthenogenetic Embryonic Stem Cells
Authors: Horii Takuro , Kimura Mika , Morita Sumiyo , Nagao Yasumitsu , Hatada Izuho
Published: October 2007

In mammals, complementary contributions of both the maternal and the paternal genomes are required for normal development because of the parental-allele-specific modification of the genome, called genomic imprinting. Therefore, parthenogenetic embryos (PG) with two maternal genomes cannot develop to term, and PG chimeras show a restricted cell contribution of donor cells and reduced weight, although they can develop to term. On the other hand, parthenogenetic embryonic stem cells (PGES) chimeras are more normal in their tissue contribution of donor cells and body weight compared with PG chimeras. To elucidate the epigenetic mechanisms underlying this, we analyzed the imprint status in donor cells of PGES and PG chimeras. In somatic lineages, genomic imprinting was lost in some PGES chimeras, whereas those in PG chimeras were almost totally maintained. Moreover, loss of imprints correlated to the gene expression pattern of imprinted genes. Therefore, this loss of imprinting in PGES chimeras could improve the tissue contribution and body weight to a normal level. On the other hand, in germ lineages, both PGES and PG in chimeras showed normal erasure of imprints, indicating that the reprogramming in germ lineages is an inevitable event, regardless of the imprint status of primordial germ cells.

Disclosure of potential conflicts of interest is found at the end of this article.
Neural Stem/Progenitor Cells Initiate the Formation of Cellular Networks That Provide Neuroprotection by Growth Factor-Modulated Antioxidant Expression
Authors: Madhavan Lalitha , Ourednik Václav , Ourednik Jitka
Published: October 2007

Recent studies indicate that transplanted neural stem/progenitor cells (NSPs) can interact with the environment of the central nervous system and stimulate protection and regeneration of host cells exposed to oxidative stress. Here, a set of animals grafted with NSPs and treated with 3-nitropropionic acid (3-NP) exhibited reduced behavioral symptoms and less severe damage of striatal cytoarchitecture than sham transplanted controls including better survival of neurons. Sites of tissue sparing correlated with the distribution pattern of donor cells in the host brain. To investigate the cellular and molecular bases of this phenomenon, we treated cocultures of NSPs and primary neural cell cultures with 3-NP to induce oxidative stress and to study NSP-dependent activation of antioxidant mechanisms and cell survival. Proactive presence of NSPs significantly improved cell viability by interfering with production of free radicals and increasing the expression of neuroprotective factors. This process was accompanied by elevated expression of ciliary neurotrophic factor (CNTF) and vascular endothelial growth factor (VEGF) in a network of NSPs and local astrocytes. Intriguingly, both in vitro and in vivo, enhanced growth factor secretion stimulated a robust upregulation of the antioxidant enzyme superoxide dismutase 2 (SOD2) in neurons and resulted in their improved survival. Our findings thus reveal a so far unrecognized mechanism of interaction between NSPs and surrounding cells accompanying neuroprotection: through mutual, NSP-triggered stimulation of growth factor production and activation of antioxidant mechanisms, cellular networks may shield the local environment from the arriving impact of oxidative stress.

Disclosure of potential conflicts of interest is found at the end of this article.
Human factors of 3‐D displays
Authors: Patterson Robert
Published: October 2007

Abstract— This paper provides a selected review of a number of important perceptual and human‐factors issues that arise when 3‐D displays are designed and used. This review and analysis draws heavily from the basic vision literature in order to help provide insight for future design solutions for 3‐D displays. Issues discussed include (1) the basics of human stereopsis, (2) interocular crosstalk, (3) oculomotor responding and distance scaling of binocular disparity information, (4) accommodative‐vergence mismatch, and (5) stereoanomly. The paper concludes with a presentation of several recommendations for the design of 3‐D displays.
A systematic framework for on‐line calibration of a head‐mounted projection display for augmented‐reality systems
Authors: Hua Hong , Gao Chunyu
Published: October 2007

Abstract—Augmented reality (AR) is a technology in which computer‐generated virtual images are dynamically superimposed upon a real‐world scene to enhance a user's perceptions of the physical environment. A successful AR system requires that the overlaid digital information be aligned with the user's real‐world senses — a process known as registration. An accurate registration process requires the knowledge of both the intrinsic and extrinsic parameters of the viewing device and these parameters form the viewing and projection transformations for creating the simulations of virtual images. In our previous work, an easy off‐line calibration method in which an image‐based automatic matching method was used to establish the world‐to‐image correspondences was presented, and it is able to achieve subpixel accuracy. However, this off‐line method yields accurate registration only when a user's eye placements relative to the display device coincides with locations established during the offline calibration process. A likely deviation of eye placements, for instance, due to helmet slippage or user‐dependent factors such as interpupillary distance, will lead to misregistration. In this paper, a systematic on‐line calibration framework to refine the off‐line calibration results and to account for user‐dependent factors is presented. Specifically, based on an equivalent viewing projection model, a six‐parameter on‐line calibration method to refine the user‐dependent parameters in the viewing transformations is presented. Calibration procedures and results as well as evaluation experiments are described in detail. The evaluation experiments demonstrate the improvement of the registration accuracy.
Novel mobile TFT‐LCDs based on SLS technology
Authors: Choi Jae Beom , Park KeeChan , Moon KookChul , Eom JiHye , Yokoyama Ryoichi , Kim ChiWoo
Published: October 2007

Abstract— Single‐crystal‐like silicon (SLS) technology is the most cost‐effective laser‐crystallization process ever invented. The throughput of the SLS process is about two times higher than that of the conventional excimer‐laser annealing (ELA) method. In addition, the performance of the TFTs fabricated by the SLS process is among the best utilized in mass production. Various TFT‐LCDs employing SLS technology, which included a 1.02‐in. full SOG LCD using an icon display for the sub‐display of cellular phones, a 1.9‐in. qVGA TFT‐LCD with a low‐power analog interface employing a low‐voltage driving scheme, and a 3.0‐in. VGA TFT‐LCD compatible with the 480i data format without additional signal processing were developed. Because the SLS process enables us to achieve highly uniform and reliable transistors, it can be effectively utilized in the mass production of mobile TFT‐LCDs with low power consumption and enhanced image quality.
Efficient and simple methods for display tone‐response characterization
Authors: Bala Raja , Klassen R. Victor , Braun Karen M.
Published: October 2007

Abstract— Color characterization is an important step towards achieving accurate color on displays. The characterization process typically uses colorimetric or spectrophotometric instruments to measure displayed colors, and relates these to digital values driving the device. Such measurements can be impractical for consumer applications. This paper presents two techniques for characterizing a display's tone response with no colorimetric or spectrophotometric measurements. The first is a visual technique applicable to devices that exhibit a “gamma” response, such as the cathode‐ray tube. The novelty lies in the replacement of the standard luminance matching with gray‐balancing for the blue channel. This approach substantially reduces observer variation in the gamma estimates for the blue channel. The second technique is applicable for the more general case of devices that do not conform to the gamma response, such as LCDs. The visual task is augmented with a consumer digital camera used as a color‐capture device. The camera tone response is first characterized via a visual task. The characterized camera is then treated as a colorimeter and used to generate a tone‐response characterization for the display. Experiments conducted on projection displays demonstrate that satisfactory quality can be achieved while eliminating the need for costly and tedious measurement.
A study on reducing image‐sticking artifacts in wide‐screen TFT‐LCD monitors
Authors: Park Yongeun , Kim Suki , Lee Eungsang
Published: October 2007

Abstract— In order to improve the image quality of flat‐panel displays, the image retention of a display has to be reduced. But at the same time, display devices also have to produce durable images while they are used for long periods of time in a single session. To achieve high‐quality images with reduced image sticking in TFT‐LCD devices, we have increased their voltage‐holding ratio (VHR). This technology ensures the achievement of durable images over long periods of time and also reduces the image‐sticking problem. There are many ways to achieve increased VHR. In terms of the characteristics of the TFT devices, reducing the leakage‐current effects is the most frequently applied method in the display industry.
Using Surfactant‐Modified Clays to Determine Sorption Mechanisms for a Representative Organic Base, Quinoline
Authors: Bonczek J. L. , Nkedi‐Kizza P.
Published: October 2007

Sorption of a representative ionizable nitrogen heterocycle, quinoline (pKa = 4.92), was investigated to determine the relative contributions of the neutral and protonated species to the overall process. Batch sorption experiments were conducted on surfactant‐modified clays that were synthesized from the exchange of hexadecyltrimethylammonium cations for resident sodium cations on a specimen smectite (Swy‐2) at 0, 60, 80, and 100% of the clay's cation exchange capacity (CEC). Hexadecyltrimethylammonium exchange creates highly effective organic partitioning domains within the clay interlayers in proportion to their coverage on the exchange complex. The fractionally exchanged clays, therefore, provided discrete exchange and organic partitioning domains for the protonated and neutral species of quinoline. Data were described by a combined Langmuir‐linear isotherm that permitted independent characterization of both sorption components. Results indicated that cationic sorption dominated but that the neutral species can contribute substantially given sufficient organic carbon content relative to the CEC and at pH above the pKa of quinoline. The data obtained in this study for quinoline demonstrated that the combined isotherm (including cation exchange and hydrophobic partitioning terms) describes sorption data and compares favorably with the purely empirical Freundlish isotherm.