bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal Structure of Receptor Neuron Input to the Olfactory Bulb Imaged in Behaving Rats
Authors: Carey Ryan M. , Verhagen Justus V. , Wesson Daniel W. , Pírez Nicolás , Wachowiak Matt
Published: December 2008

The dynamics of sensory input to the nervous system play a critical role in shaping higher-level processing. In the olfactory system, the dynamics of input from olfactory receptor neurons (ORNs) are poorly characterized and depend on multiple factors, including respiration-driven airflow through the nasal cavity, odorant sorption kinetics, receptor–ligand interactions between odorant and receptor, and the electrophysiological properties of ORNs. Here, we provide a detailed characterization of the temporal organization of ORN input to the mammalian olfactory bulb (OB) during natural respiration, using calcium imaging to monitor ORN input to the OB in awake, head-fixed rats expressing odor-guided behaviors. We report several key findings. First, across a population of homotypic ORNs, each inhalation of odorant evokes a burst of action potentials having a rise time of about 80 ms and a duration of about 100 ms. This rise time indicates a relatively slow, progressive increase in ORN activation as odorant flows through the nasal cavity. Second, the dynamics of ORN input differ among glomeruli and for different odorants and concentrations, but remain reliable across successive inhalations. Third, inhalation alone (in the absence of odorant) evokes ORN input to a significant fraction of OB glomeruli. Finally, high-frequency sniffing of odorant strongly reduces the temporal coupling between ORN inputs and the respiratory cycle. These results suggest that the dynamics of sensory input to the olfactory system may play a role in coding odor information and that, in the awake animal, strategies for processing odor information may change as a function of sampling behavior.
Activity-Dependent Plasticity Improves M1 Motor Representation and Corticospinal Tract Connectivity
Authors: Chakrabarty S. , Friel K. M. , Martin J. H.
Published: December 2008

Motor cortex (M1) activity between postnatal weeks 5 and 7 is essential for normal development of the corticospinal tract (CST) and visually guided movements. Unilateral reversible inactivation of M1, by intracortical muscimol infusion, during this period permanently impairs development of the normal dorsoventral distribution of CST terminations and visually guided motor skills. These impairments are abrogated if this M1 inactivation is followed by inactivation of the contralateral, initially active M1, from weeks 7 to 11 (termed alternate inactivation). This later period is when the M1 motor representation normally develops. The purpose of this study was to determine the effects of alternate inactivation on the motor representation of the initially inactivated M1. We used intracortical microstimulation to map the left M1 1 to 2 mo after the end of left M1 muscimol infusion. We compared representations in the unilateral inactivation and alternate inactivation groups. Alternate inactivation converted the sparse proximal M1 motor representation produced by unilateral inactivation to a complete and high-resolution proximal–distal representation. The motor map was restored by week 11, the same age that our present and prior studies demonstrated that alternate inactivation restored CST spinal connectivity. Thus M1 motor map developmental plasticity closely parallels plasticity of CST spinal terminations. After alternate inactivation reestablished CST connections and the motor map, an additional 3 wk was required for motor skill recovery. Since motor map recovery preceded behavioral recovery, our findings suggest that the representation is necessary for recovering motor skills, but additional time, or experience, is needed to learn to take advantage of the restored CST connections and motor map.
Integration of Broadband Conductance Input in Rat Somatosensory Cortical Inhibitory Interneurons: An Inhibition-Controlled Switch Between Intrinsic and Input-Driven Spiking in Fast-Spiking Cells
Authors: Tateno T. , Robinson H.P.C.
Published: December 2008

Quantitative understanding of the dynamics of particular cell types when responding to complex, natural inputs is an important prerequisite for understanding the operation of the cortical network. Different types of inhibitory neurons are connected by electrical synapses to nearby neurons of the same type, enabling the formation of synchronized assemblies of neurons with distinct dynamical behaviors. Under what conditions is spike timing in such cells determined by their intrinsic dynamics and when is it driven by the timing of external input? In this study, we have addressed this question using a systematic approach to characterizing the input–output relationships of three types of cortical interneurons (fast spiking [FS], low-threshold spiking [LTS], and nonpyramidal regular-spiking [NPRS] cells) in the rat somatosensory cortex, during fluctuating conductance input designed to mimic natural complex activity. We measured the shape of average conductance input trajectories preceding spikes and fitted a two-component linear model of neuronal responses, which included an autoregressive term from its own output, to gain insight into the input–output relationships of neurons. This clearly separated the contributions of stimulus and discharge history, in a cell-type dependent manner. Unlike LTS and NPRS cells, FS cells showed a remarkable switch in dynamics, from intrinsically driven spike timing to input-fluctuation–controlled spike timing, with the addition of even a small amount of inhibitory conductance. Such a switch could play a pivotal role in the function of FS cells in organizing coherent gamma oscillations in the local cortical network. Using both pharmacological perturbations and modeling, we show how this property is a consequence of the particular complement of voltage-dependent conductances in these cells.
Synthesis and Biological Evaluation of 7-O-Modified Formononetin Derivatives
Authors: Yang Ying , Mao Wen-Jun , Li Huan-Qiu , Zhu Tao-Tao , Shi Lei , Lv Peng-Cheng , Zhu Hai-Liang
Published: December 2008

Three series of novel formononetin derivatives were synthesized, in which formononetin and heterocyclic moieties were separated by 2-carbon, 3-carbon, and 4-carbon spacers. The chemical structures of these compounds were confirmed. All the derivatives were screened for antiproliferative activities against Jurkat cell line and HepG-2 cell line. In this paper, compounds prepared were also screened for their antibacterial activity of six bacterial strains. Compound 3b exihibited promising antibacterial activity against B. subtilis with minimal inhibitory concentration (MIC) value of 0.78 μg/mL, and compound 5e showed significant antiproliferative activities against Jurkat cell growth with IC50 of 1.35×10−4 μg/mL. The preliminary investigation of structure-activity relationships (SARs) was also discussed based on the obtained experimental data.
Discrimination of 2n = 60 Spalax leucodon cytotypes (Spalacidae, Rodentia) in Turkey by means of classical and molecular cytogenetic techniques
Authors: Ivanitskaya E. , Sözen M. , Rashkovetsky L. , Matur F. , Nevo E.
Published: December 2008

Comparative studies among seven populations of 2n = 60 S. leucodon employing classic cytogenetics (G- bands, C-bands, AgNOR-staining), fluorochrome staining, and fluorescence in situ hybridization of telomeric and rDNA probes are reported here for the first time. The studied specimens were assigned to two cytotypes: 2n = 60W and 2n = 60R. The basic karyotype of both cytotypes consisted of eight pairs of subtelocentric and 21 pairs of acrocentric autosomes, subtelocentric X and acrocentric Y chromosomes. Both cytotypes had variable numbers of B-chromosomes (1–3) and variable numbers of autosomal arms (NFa = 74–76) caused by amplification (deletion) of heterochromatin short arms in the second pair. The short arms of subtelocentric chromosomes were comprised of heterochromatin in both cytotypes. Nucleolar organizer regions (NORs) and rDNA clusters were detected at telomeric sites of the short arms in pairs Nos. 3, 5, 6, 9, and 13 in cytotype W, and in the short arms of pair No. 6, 8, 12, 13, and 16 in cytotype R. Different locations of rDNA clusters allowed unambiguous discrimination between two S. leucodon cytotypes possessing the same 2n = 60 and similar NFa (74–76) variability. Our findings suggest a high level of chromosomal divergence, which means that it is possible to consider these cytotypes as a well-differentiated, chromosomal lineage within the leucodon group.
Comparative chromosome painting between chicken and spectacled owl (Pulsatrix perspicillata): implications for chromosomal evolution in the Strigidae (Aves, Strigiformes)
Authors: de Oliveira E.H.C. , de Moura S.P. , dos Anjos L.J.S. , Nagamachi C.Y. , Pieczarka J.C. , O´Brien P.C.M. , Ferguson-Smith M.A.
Published: December 2008

The spectacled owl (Pulsatrix perspicillata), a species found in the Neotropical region, has 76 chromosomes, with a high number of biarmed chromosomes. In order to define homologies between Gallus gallus and Pulsatrixperspicillata (Strigiformes, Strigidae), we used chromosome painting with chicken DNA probes of chromosomes 1–10 and Z and telomeric sequences. This approach allowed a comparison between Pulsatrixperspicillata and other species of Strigidae already analyzed by chromosome painting (Strix nebulosa and Bubo bubo, both with 2n = 80). The results show that centric fusions and fissions have occurred in different chromosomal pairs and are responsible for the karyotypic variation observed in this group. No interstitial telomeric sequences were found. Although the largest pair of chromosomes in P. perspicillata and Bubo bubo are submetacentric, they are homologous to different chicken chromosomes: GGA1/GGA2 in P. perspicillata and GGA2/GGA4 in B. bubo.
Microdissection and whole chromosome painting. Improving sex chromosome analysis in Triportheus (Teleostei, Characiformes)
Authors: Diniz D. , Laudicina A. , Cioffi M.B. , Bertollo L.A.C.
Published: December 2008

Triportheus fish species present 2n = 52 chromosomes. The karyotypes show similar macrostructure and a ZZ/ZW sex chromosome system, which probably represents synapomorphy for the genus. A probe of the Z chromosome was obtained from T. nematurus through microdissection, followed by unspecific amplification via DOP-PCR. This probe was used for WCP (whole chromosome painting) through fluorescent in situ hybridization (FISH) in several other Triportheus species, to analyze the differentiation of the ZZ/ZW system. The homology between this probe and chromosomes of species from other genera, putatively related to Triportheus, was also examined to search for evidence about evolution of their sex chromosomes. Complete homology was found among the Z chromosomes of all Triportheus species, while only small positive signals were found on the W chromosomes. Hybridization signals were absent in species from other genera. The present results reinforce both the conservative nature of Z chromosomes and the hypothesis that the ZZ/ZW sex chromosome system is a synapomorphic feature of Triportheus. On the other hand, besides reduction of size, W chromosomes have undergone accentuated composition changes in relation to Z chromosomes, since only a small region, usually located in the short arm, kept homology with the Z chromosomes.
Imaging of Hepatocellular Carcinoma: Qualitative and Quantitative Analysis of Postvascular Phase Contrast-Enhanced Ultrasonography with Sonazoid
Authors: Inoue Tatsuo , Kudo Masatoshi , Hatanaka Kinuyo , Takahashi Syunsuke , Kitai Satoshi , Ueda Taisuke , Ishikawa Emi , Hagiwara Satoru , Minami Yasunori , Chung Hobyung , Ueshima Kazuomi , Maekawa Kiyoshi
Published: December 2008

Purpose: To evaluate the usefulness of vascular phase images of contrast-enhanced ultrasonography (CE-US) with Sonazoid for hepatocellular carcinomas (HCCs), a retrospective, comparative study was conducted of images of HCCs obtained by CE-US and superparamagnetic iron oxide (SPIO) magnetic resonance imaging (MRI) and evaluated qualitatively and quantitatively. Methods: Seventy-seven patients with 88 HCCs who received CE-US and SPIO-MRI were reviewed. The ratio of the echogenicity of the tumor and nontumor areas was calculated with postvascular phase CE-US (postvascular phase ratio). The ratio of the intensity of the nontumor to tumor areas on SPIO-enhanced MRI (SPIO intensity index) was also calculated. The Pearson correlations were calculated for all values between the postvascular phase ratio and SPIO intensity index for quantitative comparison. These images were also compared qualitatively for the detection rate of the tumors. Results: The sensitivities of CE-US and SPIO-MRI in detecting tumors were 98 and 95%, respectively (nonsignificant, χ2 test). The postvascular phase ratio correlated with the SPIO intensity index for HCCs (Pearson r = 0.803, p < 0.05). The image conformity of the result from the liver parenchymal phase CE-US and SPIO-MRI was 92%. Dedifferentiation spots of nodule-in-nodule HCCs were detected in 4 (80%) of 5 on postvascular phase images of CE-US, and in 2 (40%) of 5 on SPIO-MRI (nonsignificant, χ2 test). Conclusions: Postvascular phase images of CE-US with Sonazoid appear promising as an alternative to SPIO-enhanced MRI. Further study cases are needed to confirm the usefulness of postvascular phase images of CE-US compared to SPIO-MRI for the detection of dedifferentiation foci in hepatic tumors.
Intranodular Blood Supply Correlates Well with Biological Malignancy Grade Determined by Tumor Growth Rate in Pathologically Proven Hepatocellular Carcinoma
Authors: Kudo Masatoshi , Tochio Hitoshi
Published: December 2008

This study was carried out to investigate whether intranodular blood supply in histologically proven well-differentiated hepatocellular carcinomas (HCCs) correlates with tumor growth rates. A total of 52 well-differentiated HCCs were enrolled in this study. Ultrasound angiography with intra-arterial CO2 microbubble injection was performed in all 52 HCCs and computed tomography during arterial portography was performed in 21 of the 52 HCCs. Tumor volume doubling time (TVDT) was measured in all 52 nodules by B-mode ultrasonography performed at 2- to 3-month intervals for a follow-up period of at least 6 months (range: 6 months to 8 years) with respect to arterial vascularity. In the hypervascular (n = 27), isovascular (n = 9), and hypovascular nodules (n = 16), the mean values of TVDT (mean ± SD) were 79 ± 131, 98 ± 227, and 782 ± 324 days, respectively (rs = 0.722, p < 0.0001). Concerning portal blood supply, the mean TVDT in nodules in which the portal supply was reduced (n = 5) was 178 ± 78 days compared with 592 ± 211 days in nodules in which the portal supply was preserved (n = 11), with a significant difference (p < 0.01). Five nodules in which the portal supply was preserved did not enlarge during the follow-up period of 3–5 years. There was a significant correlation among the three groups (rs = 0.804, p < 0.05). In conclusion, intranodular blood flow dynamics in patients with well-differentiated HCC reflect the biological malignancy or cancer progression in the process of multistep hepatocarcinogenesis, suggesting the importance of this parameter in deciding on a treatment strategy. In other words, nodules in which arterial vascularity is present and those in which the portal blood flow is reduced should be treated for reasons such as a short doubling time and the risk of rapid progression to artery-dominant classical HCC.
Combination Therapy with S-1 and Pegylated Interferon Alpha for Advanced Hepatocellular Carcinoma
Authors: Ueshima Kazuomi , Kudo Masatoshi , Nagai Tomoyuki , Tatsumi Chie , Ueda Taisuke , Takahashi Shunsuke , Hatanaka Kinuyo , Kitai Satoshi , Ishikawa Emi , Inoue Tatsuo , Hagiwara Satoru , Minami Yasunori , Chung Hobyung
Published: December 2008

Purpose: There are currently no effective treatments for patients with advanced hepatocellular carcinoma (HCC) with vascular invasion or extrahepatic metastases. We evaluated the efficacy and safety of combination therapy with S-1 and pegylated interferon (PEG-IFN)-α for advanced HCC. Methods: A total of 22 patients received combination therapy with S-1 and PEG-IFN. One cycle of the combination therapy consists of oral S-1 (80 mg/m2) administration and subcutaneous PEG-IFN injection (PEG-IFN-α-2a 90 μg weekly or PEG-IFN-α-2b 50 μg weekly) for 4 weeks with 1- to 2-week intervals. Results: One patient was evaluated as complete response, 6 as partial response, 8 as stable disease, and 6 as progressive disease. One patient was not evaluable because therapy had to be discontinued as a result of jaundice. The median survival time was 15.3 months (95% CI: 4.4–26.2 months). The 1- and 2-year survival rates were 54.9 and 36.6%, respectively. The overall response rate was 31.8% and the disease control rate was 68.2%. Grade 3 neutropenia (18.2%), leukopenia (9.1%), anemia (9.1%), and thrombocytopenia (18.2%) were observed. Grade 4 toxicities were not observed. Conclusion: Combination therapy with S-1 and PEG-IFN is effective and feasible, and is therefore a promising regimen for advanced HCC.
Systemic Chemotherapy of Hepatocellular Carcinoma – Korean Experience
Authors: Lee Han Chu
Published: December 2008

Surgical resection, transarterial chemoembolization, percutaneous ethanol injection therapy, radiofrequency ablation, and orthotopic liver transplantation are generally accepted treatment modalities in hepatocellular carcinoma, but there has been no standard therapy for patients at the advanced stage. Several combinations of various cytotoxic agents have been tried in Korea, but definite conclusions could not be drawn because of small sample size, heterogenous populations among studies, several biases, and lack of a control arm. There has been no evidence so far that either of the combination chemotherapies is superior to single-agent chemotherapy or systemic chemotherapy has any clinical benefit in terms of patient survival. Recent advances in molecular biology have identified several important signal transduction pathways during hepatocarcinogenesis, which enables us to control the key elements of these signaling pathways. Accordingly, several new ‘targeted agents’ have been developed and are under clinical trial at present. In contrast to previous cytotoxic agents, most targeted agents do not induce regression of tumors but stabilize disease progression. Sorafenib is the first drug proven to prolong survival in advanced stage patients. However, the survival benefit is still not satisfactory; therefore, future trials should be conducted regarding the combination of sorafenib with other preexisting treatment modalities or new targeted agents.
Functional Magnetic Resonance Imaging of Compensatory Neural Recruitment in Aging and Risk for Alzheimer’s Disease: Review and Recommendations
Authors: Han S. Duke , Bangen Katherine J. , Bondi Mark W.
Published: December 2008

There has been a recent proliferation of functional magnetic resonance imaging (fMRI) studies that interpret between-group or within-group differences in brain response patterns as evidence for compensatory neural recruitment. However, it is currently a challenge to determine whether these observed differences are truly attributable to compensatory neural recruitment or whether they are indicative of some other cognitive or physiological process. Therefore, the need for a standardized set of criteria for interpreting whether differences in brain response patterns are compensatory in nature is great. Focusing on studies of aging and potentially prodromal Alzheimer’s disease conditions (genetic risk, mild cognitive impairment), we critically review the functional neuroimaging literature purporting evidence for compensatory neural recruitment. Finally, we end with a comprehensive model set of criteria for ascertaining the degree to which a ‘compensatory’ interpretation may be supported. This proposed model addresses significant brain region, activation pattern, and behavioral performance considerations, and is therefore termed the Region-Activation-Performance model (RAP model).
Plasma Homocysteine and Risk of Mild Cognitive Impairment
Authors: Reitz Christiane , Tang Ming-Xin , Miller Joshua , Green Ralph , Luchsinger José A.
Published: December 2008

Background and Objective: There are conflicting data relating homocysteine levels to the risk of Alzheimer’s disease (AD). We sought to explore whether fasting plasma homocysteine is associated with the risk of mild cognitive impairment (MCI), an intermediate stage to dementia. Methods: Fasting levels of plasma homocysteine were obtained from 678 elderly subjects chosen at random from a cohort of Medicare recipients. There were longitudinal data in 516 subjects without MCI or dementia at baseline who were followed for 2,705 person-years. The relation of plasma homocysteine with prevalent and incident all-cause MCI, amnestic MCI and non-amnestic MCI was assessed using logistic and Cox proportional hazards regression analyses. Results: There were 162 cases of prevalent MCI and 132 cases of incident MCI in 5.2 years of follow-up. There was no association between plasma homocysteine and prevalence of MCI or amnestic or non-amnestic MCI in the cross-sectional analyses. There was no association between higher homocysteine levels and a lower risk of all-cause MCI. Consistent with the cross-sectional analyses, there was no specific association with the amnestic or non-amnestic subtype of MCI in crude or adjusted models. Conclusion: Plasma homocysteine levels measured at baseline were not related to MCI or its subtypes in an elderly multiethnic cohort.
Vascular Anatomy of the Hamster Retractor Muscle with Regard to Its Microvascular Transfer
Authors: de With M.C.J. , de Vries A.M. , Kroese A.B.A. , van der Heijden E.P.A.B. , Bleys R.L.A.W. , Segal S.S. , Kon M.
Published: December 2008

Background: The hamster retractor muscle (RET) is used as an in vivo model in studies of skeletal muscle ischemia-reperfusion injury. The RET is unique in that the muscle can be isolated while preserving the primary vascular supply so that its contractile function can be measured simultaneously with local microvascular responses to experimental interventions. The goal of this study was to understand the anatomical origin of the vascular supply to the RET and determine whether the RET can be used as a free flap after surgical isolation of the thoracodorsal vessels. Methods: Microdissection was performed to determine the anatomy of the vasculature that supplies and drains the RET. Results: Distinct numbers and patterns of feed arteries (2–4) and collecting veins (1–3) were identified (n = 26 animals). Dye injection (n = 8) of the thoracodorsal artery demonstrated that the RET remains perfused following its isolation on the thoracodorsal pedicle. Heterotopic allograft transplantation of the RET (n = 2) was performed by anastomosing the thoracodorsal vessels to the femoral vessels using the end-to-side technique. Conclusions: The anatomical relationships indicate that the RET can be used as a free flap model for evaluating the effect of preservation strategies and transplantation on skeletal muscle microcirculation and contractile function.
Clinicoepidemiological Profiles and Outcomes during First Hospital Admission of Head Injury Patients in Ikeja, Nigeria
Authors: Adeleye A.O. , Olowookere K.G. , Olayemi O.O.
Published: December 2008

Background: Although head injury (HI) is a major public health problem in Nigeria and other low and middle income countries of the world, there is a paucity of data from these societies. This is largely due to under-reporting. We carried out a prospective study of the clinicoepidemiological profiles and outcomes following the first hospitalization of a cohort of head-injured patients in Ikeja, Nigeria, a metropolitan African city. Methods: In an 8-month period from May until December 2005, data from all HI cases seen in our neurosurgical unit were prospectively recorded for subsequent analysis. These include demographics, mechanism of injury, pre-neurosurgical care received, severity of injury using the Glasgow Coma Scale, presence of hemodynamic instability, pupillary anomalies and associated systemic injuries, cranial computed tomography (CT) findings and the number of surgical interventions, as well as outcomes after the first hospital admission using the Glasgow Outcome Scale. Determinants of outcome were explored using the χ2 test and the level of significance was put at p = 0.05. Results: There were 143 cases of HI, which is about one fifth of our total workload, including 122 males and 21 females aged 0.5–85 years (mean age 29.15). The majority (88%) were either school children or low income earners. Road accidents accounted for 75% of the cases; three quarter of the cases had some initial care in other health facilities before the arrival in our unit, at an average of 33 h. Mild, moderate and severe HI accounted for 60, 18 and 22%, respectively. About a quarter of the patients sustained other systemic injuries. Cranial CT scanning was obtainable in 40 patients (28%); 9 of these revealed surgical mass lesions, of whom 5 had life-saving operations. Many well-known determinants of a poor outcome of HI were prevalent in this study group and found to have a significantly adverse effect on patient outcome. Conclusions: HI is a major public health problem in Nigeria, taking up at least one fifth of the neurosurgical workload. The prehospital emergency medical service is poorly organized. Determinants of a poor outcome of HI are highly prevalent, including poor accessibility to cranial CT scanning, absence or inadequacy of logistics for neurocritical care and an inadequate number of neurosurgeons.
Cognitive Performance and Grey Matter Density in Psychosis: Functional Relevance of a Structural Endophenotype
Authors: Habets P. , Krabbendam L. , Hofman P. , Suckling J. , Oderwald F. , Bullmore E. , Woodruff P. , Van Os J. , Marcelis M.
Published: December 2008

Background: Structural brain changes and cognitive impairments have been identified as indicators of genetic risk for schizophrenia. However, the pattern of associations between such structural and functional liability markers has been less well investigated. Methods: Magnetic resonance imaging data and cognitive assessments were acquired in 31 patients with psychosis, 32 non-psychotic first-degree relatives and 28 controls. The relationship between cerebral grey matter density and cognitive performance was examined using computational morphometry. Results: Two out of 6 cognitive tests revealed significant associations with grey matter density in regions of the frontal lobe, basal ganglia, thalamus and cerebellum in patients and relatives. In patients, poorer executive functioning was associated with cerebellar grey matter density deficits. In relatives, poorer executive functioning was associated with increased grey matter density in the cerebellum and frontal lobe. In both patients and relatives, strategic retrieval from semantic memory was positively associated with grey matter density in basal ganglia structures. Some additional negative associations in the patients differentiated this group from relatives. Conclusions: The overlap in structure-function relationships in individuals with schizophrenia and those with liability for the disorder may suggest that regional grey matter density alterations functionally alter particular neurocircuits, which could lead to cognitive deficits. The non-overlapping structure-function correlations may reflect disease-related or compensatory mechanisms.
Serum and Tissue LDH Levels in Patients with Breast/Gynaecological Cancer and Benign Diseases
Authors: Koukourakis Michael I. , Kontomanolis Emmanuel , Giatromanolaki Alexandra , Sivridis Efthimios , Liberis Vassilios
Published: December 2008

Background: Lactate dehydrogenase A (LDHA) is involved in anaerobic glycolysis. In cancer patients, serum total lactate dehydrogenase (LDH) levels are often increased, and the gene for one of its isoenzymes, LDHA, is up-regulated. These features have been linked to poor prognosis in several studies. Methods: We investigated comparatively the total serum LDH activity and tissue isoenzyme LDH5 and hypoxia-inducible factor 1α (HIF1α) levels in patients with breast (n = 18) and gynaecological (n = 23) malignancies and benign diseases (n =54). Results: The serum LDH levels were significantly higher in patients with endometrial adenocarcinoma (349 ± 100 IU/l) and ovarian cystadenocarcinomas (383 ± 116 IU/l) compared to healthy controls (256 ± 68 IU/l) (p values 0.01 and 0.006, respectively). This difference did not reach significance in patients with breast cancer (328 ± 169 IU/l; p = 0.17)). Uterine leiomyoma patients showed intermediate LDH levels (310 ± 81 IU/l), while patients with breast fibroadenomas and ovarian cystadenomas had LDH serum levels close to carcinomas (308 ± 60 and 348 ± 135 IU/l, respectively). LDH5 isoenzyme was strongly expressed in cancer cells, exhibiting a mixed cytoplasmic/nuclear subcellular pattern. Interestingly, a high LDH5 content in tissue sections was not invariably accompanied by high LDH serum levels. High HIF1α tissue expression was linked to high tissue LDH5 expression. Conclusion: Serum and tissue LDH is up-regulated in gynaecologic and breast malignancies and in a subset of benign conditions such as fibro- and cystadenomas. The release of LDH, however, in the bloodstream is partly related to the LDHA gene up-regulation.
Early Intravitreal Bevacizumab for Non-Ischaemic Branch Retinal Vein Occlusion
Authors: Rensch Florian , Jonas Jost B. , Spandau Ulrich H.M.
Published: December 2008

Purpose: To evaluate the effect of early intravitreal bevacizumab application in patients with macular oedema due to non-ischaemic branch retinal vein occlusion (BRVO). Procedures: The study included 21 patients (21 eyes) with macular oedema due to non-ischaemic BRVO. Inclusion criteria were significant macular oedema as measured by optical coherence tomography, loss of visual acuity and leakage in fluorescence angiography. All patients received 3 intravitreal injections of 1.5 mg bevacizumab. The mean follow-up was 6.2 ± 1.2 months (mean ± standard deviation). The mean duration of the BRVO prior to treatment was 9.2 ± 5.4 days. Results: The visual acuity improved significantly from baseline 0.81 ± 0.53 logMAR to 0.54 ± 0.47 logMAR (p < 0.001) at 1 month, 0.55 ± 0.46 (p = 0.001) at 3 months and to 0.55 ± 0.49 (p = 0.002) at 6 months after the first injection. The mean central retinal thickness decreased significantly (p < 0.001) from 492 ± 113 μm at baseline to 294 ± 117 μm at 1 month after the first injection to 325 ± 127 μm at 3 months (p < 0.001) and to 316 ± 117 μm at 6 months (p < 0.001) after the first injection. The increase in visual acuity correlated significantly (p < 0.01) with the decrease in macular thickness. Conclusions: Early intravitreal injection of bevacizumab may decrease macular oedema and improve visual acuity in eyes with non-ischaemic BRVO.
Influence of Ethanol on the Solubility, Ionization and Permeation Characteristics of Ibuprofen in Silicone and Human Skin
Authors: Watkinson R.M. , Herkenne C. , Guy R.H. , Hadgraft J. , Oliveira G. , Lane M.E.
Published: December 2008

In the context of topical and transdermal delivery, cosolvents may be expected to enhance solubility, modify drug partitioning behaviour and alter skin barrier properties. In the present study, we have investigated systematically the influence of increasing amounts of the cosolvent ethanol on the solubility, ionization, and permeability characteristics of ibuprofen in silicone and in skin. The possibility of ibuprofen self-association was also examined. As the amount of ethanol was raised from 0 to 100%, ibuprofen solubility was enhanced 5,500-fold relative to its aqueous solubility. Up to 50%, the pKa of ibuprofen shifted from 4.44 to 5.68. Infrared spectroscopy confirmed the presence of ibuprofen in both monomer and dimer forms in vehicles containing 75 and 100% ethanol. In silicone membranes, the flux of ibuprofen increased 8-fold over the range of ethanol concentrations studied (0–100%) relative to aqueous solutions, with the highest flux observed for 100% ethanol. However, in skin, the flux of ibuprofen was optimal for 50:50 and 75:25 ethanol-water vehicles (>10-fold flux enhancement). The lower ibuprofen flux from pure ethanol may reflect the alcohol’s ability to dehydrate human skin. In general, the flux data confirm that increasing ethanol content enhances the solubility of ibuprofen in silicone and human skin as well as in the vehicle itself.
Possibility of Topical Antioxidant Treatment of Cataracts: Corneal Penetration of Pyruvate in Humans
Authors: Chandra P. , Hegde K.R. , Varma S.D.
Published: December 2008

Aim: It was our aim to study the penetration of sodium pyruvate into the aqueous humor of humans after its topical application as an eye drop. Methods: Two hours prior to surgery, one drop of 5% sodium pyruvate prepared in artificial tears was instilled in the eye to be operated upon for cataract extraction. The drops were given 4 times at 10-min intervals. Eye drops containing tropicamide, phenylephrine, flurbiprofen and tobramycin were also given preoperatively. At the start of surgery, an aqueous sample was withdrawn, kept refrigerated and analyzed for pyruvate within 2 h. The cataracts were then extracted either by routine extracapsular extraction or by phacoemulsification, both followed by intraocular lens implantation. The pyruvate level was determined colorimetrically by reacting it with 2,4-dinitrophenyl hydrazine. Results: The level of pyruvate in the aqueous sample of patients that did not receive pyruvate eye drops was only 0.145 ± 0.06 mM. In the group given pyruvate, it increased to approximately 0.35–0.525 mM. Conclusion: The results demonstrate that topical administration of pyruvate is effective in elevating its concentration in the aqueous humor to a level adequate to offer protection against oxidative stress to the lens and other intraocular tissues. Hence, it should be feasible to carry out clinical trials with this compound aimed at treating diseases such as cataracts and diabetic retinopathy induced by generation of reactive oxygen species and consequent oxidative stress.
Patient Satisfaction after Laparoscopic Total or Supracervical Hysterectomy
Authors: Kafy Souzan , Al-Sannan Baydaa , Kabli Nadia , Tulandi Togas
Published: December 2008

Background/Aims: To evaluate patient satisfaction after laparoscopic supracervical (LASH) or total hysterectomy (TLH). Methods: Retrospective study of patient satisfaction after LASH or TLH. Results: We studied 40 cases of LASH and another 40 of TLH. The age of the patients, marital status, education level and employment status between the two groups were comparable. Both LASH and TLH results in improvement of general health and symptoms. However, there was no significant difference in patient satisfaction with surgery, in general health, body and self-images, and sexual satisfaction between the LASH and TLH group. Before surgery, patients in the TLH group experienced more pain with a sexual relationship than those in the LASH group. The difference became non-significant after surgery. There was no difference in urinary or gastrointestinal symptoms after either type of hysterectomy. Conclusions: Both LASH and TLH result in improvement of general health and symptoms. Body and self-images, sexual function, gastrointestinal and urinary functions after LASH or TLH are comparable.
Acute Treatment Costs of Stroke in Brazil
Authors: Christensen Michael C. , Valiente Raul , Sampaio Silva Gisele , Lee Won Chan , Dutcher Sarah , Guimarães Rocha Maria Sheila , Massaro Ayrton
Published: December 2008

Background and Purpose: Although stroke is the leading cause of death in Brazil, little information exist on the acute treatment provided for stroke and its associated costs. This study addresses this gap by both clinically and economically characterizing the acute treatment of first-ever intracerebral hemorrhage (ICH) and ischemic stroke (IS) in Brazil. Methods: Retrospective medical chart review using data from two high-volume stroke centers in São Paulo, Brazil. Clinical and resource utilization data for all patients admitted to the stroke centers with a first-ever stroke between January 1, 2006 and May 31, 2007 were collected and the mean acute treatment costs per person were calculated by assigning appropriate unit cost data to all resource use. Cost estimates in Brazilian reals (BRL) were converted to US dollars (USD) using the 2005 purchasing power parity index. National costs of acute treatment for incident strokes were estimated by extrapolation of mean cost estimate per person to national incidence data for the two types of stroke. The mean costs of acute treatment on a national scale were examined in sensitivity analysis. Results: A total of 316 stroke patients were identified and their demographic and clinical characteristics, patterns of care, and outcomes were examined. Mean length of hospital stay was 12.0 ± 8.8 days for ICH and 13.3 ±23.4 days for IS. Ninety-one percent of the ICH patients and 68% of the IS patients were admitted to an intensive care unit (ICU). Mean total costs of initial hospitalization were USD 4,101 (SD ±4,254) for ICH and USD 1,902 (SD ±1,426) for IS. In multivariate analysis, hemorrhagic stroke, development of pneumonia, neurosurgical intervention, stay in ICU, and physical therapy were all significant independent predictors of acute treatment costs. Aggregate national health care expenditures for acute treatment of incident ICH were USD 122.4 million (range 30.8–274.2) and USD 326.9 million for IS (range 82.4–732.2). Conclusion: Acute treatment costs of incident ICH and IS in Brazil are substantial and primarily driven by the intensity of hospital treatment and in-hospital complications. With the expected increase in the incidence of stroke in Brazil over the coming decades, these results emphasize the need for effective preventive and acute medical care.
The Effect of N-Acetylcysteine on Proteinuria and Markers of Tubular Injury in Non-Diabetic Patients with Chronic Kidney Disease
Authors: Renke Marcin , Tylicki Leszek , Rutkowski Przemysław , Larczyński Wojciech , Aleksandrowicz Ewa , Łysiak-Szydłowska Wiesława , Rutkowski Bolesław
Published: December 2008

Background: Inhibition of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors (ACEI) and/or angiotensin II subtype 1 receptor antagonists (ARB) constitutes a strategy in the management of patients with chronic kidney disease. There is still no optimal therapy which can stop the progression of chronic kidney disease. Antioxidants such as N-acetylcysteine (NAC) have been reported as a promising strategy in this field. Methods: In a placebo-controlled, randomized, open, 2-period cross-over study, we evaluated the influence of NAC (1,200 mg/day) added to renin-angiotensin-aldosterone system blockade on proteinuria and surrogate markers of tubular injury and renal fibrosis in 20 non-diabetic patients with proteinuria (0.4–6.36 g/24 h) with normal or decreased kidney function (estimated glomerular filtration rate 61–163 ml/min). Subjects entered the 8-week run-in period during which the therapy using ACEI and/or ARB was established with blood pressure below 130/80 mm Hg. Next, patients were randomly assigned to 1 of 2 treatment sequences: NAC/washout/placebo or placebo/washout/NAC. Clinical evaluation and laboratory tests were performed at the randomization point and after each period of the study. Results: No significant changes in laboratory tests were observed. Conclusion: NAC had no effect on proteinuria, surrogate markers of tubular injury or renal fibrosis in non-diabetic patients with chronic kidney disease.
Neuropeptide Urocortin 1 and Its Receptors Are Expressed in the Human Liver
Authors: Simopoulos Constantinos , Christodoulou Eirini , Lambropoulou Maria , Tsaroucha Alexandra K. , Kakolyris Stylianos , Polychronidis Alexandros , Karayiannakis Athanassios J. , Chatzaki Ekaterini
Published: December 2008

The corticotropin-releasing hormone (CRH) system, consisting of CRH, urocortins (Ucns), their receptors CRH1 and CRH2, and CRH-binding protein, holds the principal role in mediating the response to stress stimuli. Besides their expression in the brain, CRH neuropeptides and receptors have been found in multiple peripheral sites. We investigated the expression of the CRH system in the human liver, using RT-PCR and immunohistochemistry. Ucn 1 gene transcripts were amplified in all the human liver biopsies examined. Ucn 1 immunoreactivity was localized in hepatocytes. CRH1 and CRH2(α) receptor gene expression was also found, and receptor protein had a similar distribution to Ucn 1. Finally, Ucn 1 and CRH receptor expression was demonstrated in hepatic biopsies from a variety of liver pathologies, including primary or metastatic liver carcinoma and cirrhosis. We conclude that the CRH system is expressed by human liver under normal and pathological conditions, Ucn 1 being the major ligand. Further study is required to unfold the biological role of these effectors in liver physiology and pathogenesis, as they may act in an autocrine manner through activation of the CRH receptors expressed locally.
Surgical Removal of Perirenal and Epididymal Adipose Tissue Decreases Serum Leptin Concentration and Increases Lipogenic Enzyme Activities in Remnant Adipose Tissue of Old Rats
Authors: Nogalska Anna , Stelmanska Ewa , Sledzinski Tomasz , Swierczynski Julian
Published: December 2008

Background: The rate of lipogenesis and gene expression of lipogenic enzymes in white adipose tissue (WAT) of rats decreases with age. Previously, we showed the inverse relationship between serum leptin concentration and lipogenic enzymes activities in WAT of ageing rats. Based on those results, we postulated that leptin could play some role in the downregulation of lipogenic enzyme genes expression in WAT of old rats. Objective: To further test this hypothesis, in the present paper we examined the effect of surgical removal of perirenal and epididymal WAT on serum leptin concentration and lipogenic enzymes activities in remnant adipose tissue of old rats. Methods: One-year-old rats, which display a high serum leptin concentration and low lipogenic enzyme activities in WAT, were subjected to surgical removal of the perirenal and epididymal WAT. Two months after the surgery, the serum leptin concentration and lipogenic enzyme activities in remnant WAT were compared to the serum leptin concentration and lipogenic enzyme activities measured in adipose tissue collected during the surgery. Results: WAT removal resulted in an approximately 6-fold decrease of serum leptin concentration and about a 2-fold increase of lipogenic enzyme activities in remnant adipose tissue. Conclusions: These results indicate that interventions designed to reduce abdominal adipose tissue mass can change the lipogenic activity of remnant adipose tissue. Additionally, leptin could be one of the factors contributing to the downregulation of the genes expression of lipogenic enzymes during ageing in rats.
Health-Related Quality of Life in Patients with Neurofibromatosis Type 1
Authors: Kodra Yllka , Giustini Sandra , Divona Luigina , Porciello Roberto , Calvieri Stefano , Wolkenstein Pierre , Taruscio Domenica
Published: December 2008

Background/Aims: Neurofibromatosis type 1 (NF1), a genetic condition most commonly characterized by the presence of dermal neurofibromas and café au lait macules, has a significant impact upon quality of life (QoL). The study aimed to assess the impact of NF1 on QoL. Methods: A total of 129 patients with NF1 completed the study questionnaires in an Italian academic dermatological centre and a neurofibromatosis clinic at the University of Rome. Results: All domains of general-health-related QoL were affected.Patients with serious cosmetic problemsreported a greater impact on the emotional domain. Conclusion: In our study, the impact of the cosmetic features on QoL had the greatest importance. This survey demonstrates the usefulness of QoL measurements in supplementing clinical assessments.
Increased Insulin Sensitivity by Metformin Enhances Intense-Pulsed-Light-Assisted Hair Removal in Patients with Polycystic Ovary Syndrome
Authors: Rezvanian Hassan , Adibi Neda , Siavash Mansour , Kachuei Ali , Shojaee-Moradie Fariba , Asilian Ali
Published: December 2008

Background: Polycystic ovary syndrome (PCOS) is an insulin-resistant state with hirsutism as a common manifestation. Objective: We hypothesized that treatment with metformin would improve the cosmetic effects of intense pulsed light (IPL) therapy for hair removal in PCOS patients. Methods: In a prospective randomized controlled trial, 70 PCOS patients randomly received metformin (1,500 mg daily) + IPL therapy or IPL therapy alone for 5 IPL sessions during a 6-month period, followed by an additional 6 months of observation. Hirsutism score, homeostasis model assessment for insulin resistance (HOMA-IR), free androgen index (FAI) and patient satisfaction were evaluated at every visit. Results: Fifty-two patients finished the study. Hirsutism was significantly better controlled in the metformin group (p = 0.009). Patient satisfaction was significantly better in the metformin group at the end of the observation period (52.9 vs. 34.1%, p = 0.019). HOMA-IR and FAI scores improved after metformin + IPL treatment (p < 0.05). Conclusion: Adding metformin to IPL in women with PCOS results in a significant improvement in insulin sensitivity and hirsutism.
Impacts of Climate Change on the Subduction of Mode and Intermediate Water Masses in the Southern Ocean
Authors: Downes Stephanie M. , Bindoff Nathaniel L. , Rintoul Stephen R.
Published: December 2008

Changes in the temperature, salinity, and subduction of Subantarctic Mode Water (SAMW) and Antarctic Intermediate Water (AAIW) between the 1950s and 2090s are diagnosed using the CSIRO Mark version 3.5 (Mk3.5) climate system model Caps under a CO2 forcing that reaches 860 ppm by the year 2100. These Southern Ocean upper-limb water masses ventilate the ocean interior, and changes in their properties have been related to climate change in numerous studies. Over time, the authors follow the low potential vorticity and salinity minimum layers describing SAMW and AAIW and find that the water column in the 2090s shifts to lighter densities by approximately 0.2 kg m−3. The model projects a reduction in the SAMW and AAIW annual mean subduction rates as a result of a combination of a shallower mixed layer, increased potential vorticity at the base of the mixed layer, and a net buoyancy gain. There is little change in the projected total volume of SAMW transported into the ocean interior via the subduction process; however, the authors find a significant decrease in the subduction of AAIW. The authors find overall that increases in the air–sea surface heat and freshwater fluxes mainly control the reduction in the mean loss of the SAMW and AAIW surface buoyancy flux when compared with the effect of changes supplied by Ekman transport because of increased zonal wind stress. In the A2 scenario, there are cooling and freshening on neutral density surfaces less than 27.3 kg m−3 in response to the warming and freshening observed at the ocean’s surface. The model projects deepening of density surfaces due to southward shifts in the outcrop regions and the downward displacement of these surfaces north of 45°S. The volume transport across 32°S is predicted to decrease in all three basins, with southward transport of SAMW and AAIW decreasing by up to 1.2 and 2.0 Sv (1 Sv ≡ 106 m3 s−1), respectively, in the Indian Ocean. These projected reductions in the subduction and transport of mode and intermediate water masses in the CSIRO Mk3.5 model could potentially decrease the absorption and storage of CO2 in the Southern Ocean.