bluuebunny/crossref_metadata_2025 huggingface dataset:
New algorithm for assessing patient suitability for macular translocation surgery
Authors: Uppal Gurmit , Milliken Andrew , Lee John , Acheson James , Hykin Phil , Tufail Adnan , Da Cruz Lyndon
Published: July 2007

Abstract

Purpose:  We propose a case selection algorithm to assess suitability for macular translocation for subfoveal neovascular membrane (CNV) secondary to age‐related macular degeneration. The algorithm is based on preoperative assessment of residual foveal function, as assessed by a slit‐lamp fixation task and duration of visual loss, in patients with poor acuity. We validate our slit‐lamp fixation task against an objective analysis (Nidek MP‐1 Microperimetry) and proceed to examine surgical outcomes as selected by the algorithm.

Methods:  A prospective series of 27 consecutive patients with CNV underwent translocation at Moorfields Eye Hospital, London between May 2003 and May 2006.

Results:  Validation of the slit‐lamp fixation task revealed 100% concordance in classification of fixation between the slit‐lamp task and the microperimeter. At an average follow up of 12.2 months, the mean Early Treatment of Diabetic Retinopathy Study distance acuity improved from logMAR 0.88 to 0.68 (P < 0.03). Sixty‐six per cent of patients achieved an acuity of ≤logMAR 0.8 (6/30), 22% an acuity of ≤logMAR 0.3 (6/12) and 33% gained three lines of acuity. The mean MN Read reading acuity improved from logMAR 1.23 to 0.91 (P < 0.01). Forty‐four per cent of patients achieved an acuity of ≥logMAR 0.7 (N10), 15% an acuity of ≥logMAR 0.4 (N5) and 44% gained three lines of acuity.

Discussion:  We have demonstrated a simple case selection algorithm that is based on residual foveal function and suggests good outcomes. The strongest indicators of foveal function are fixation characteristics and duration of visual loss. In contrast to previous studies, our algorithm suggests good outcomes independently of preoperative visual acuity and CNV characteristics.
Genetic testing for retinal dystrophies and dysfunctions: benefits, dilemmas and solutions
Authors: Koenekoop Robert K , Lopez Irma , Den Hollander Anneke I , Allikmets Rando , Cremers Frans PM
Published: July 2007

Abstract

Human retinal dystrophies have unparalleled genetic and clinical diversity and are currently linked to more than 185 genetic loci. Genotyping is a crucial exercise, as human gene‐specific clinical trials to study photoreceptor rescue are on their way. Testing confirms the diagnosis at the molecular level and allows for a more precise prognosis of the possible future clinical evolution. As treatments are gene‐specific and the ‘window of opportunity’ is time‐sensitive; accurate, rapid and cost‐effective genetic testing will play an ever‐increasing crucial role. The gold standard is sequencing but is fraught with excessive costs, time, manpower issues and finding non‐pathogenic variants. Therefore, no centre offers testing of all currently 132 known genes. Several new micro‐array technologies have emerged recently, that offer rapid, cost‐effective and accurate genotyping. The new disease chips from Asper Ophthalmics (for Stargardt dystrophy, Leber congenital amaurosis [LCA], Usher syndromes and retinitis pigmentosa) offer an excellent first pass opportunity. All known mutations are placed on the chip and in 4 h a patient's DNA is screened. Identification rates (identifying at least one disease‐associated mutation) are currently ∼70% (Stargardt), ∼60–70% (LCA) and ∼45% (Usher syndrome subtype 1). This may be combined with genotype–phenotype correlations that suggest the causal gene from the clinical appearance (e.g. preserved para‐arteriolar retinal pigment epithelium suggests the involvement of the CRB1 gene in LCA). As ∼50% of the retinal dystrophy genes still await discovery, these technologies will improve dramatically as additional novel mutations are added. Genetic testing will then become standard practice to complement the ophthalmic evaluation.
Magnetic resonance imaging in the detection of pancreatic neoplasms
Authors: ZHONG Liang
Published: July 2007

Recently, with the rapid scanning time and improved image quality, outstanding advances in magnetic resonance (MR) methods have resulted in an increase in the use of MRI for patients with a variety of pancreatic neoplasms. MR multi‐imaging protocol, which includes MR cross‐sectional imaging, MR cholangiopancreatography and dynamic contrast‐enhanced MR angiography, integrates the advantages of various special imaging techniques. The non‐invasive all‐in‐one MR multi‐imaging techniques may provide the comprehensive information needed for the preoperative diagnosis and evaluation of pancreatic neoplasms. Pancreatic neoplasms include primary tumors and pancreatic metastases. Primary tumors of the pancreas may be mainly classified as ductal adenocarcinomas, cystic tumors and islet cell tumors (ICT). Pancreatic adenocarcinomas can be diagnosed in a MRI study depending on direct evidence or both direct and indirect evidence. The combined MRI features of a focal pancreatic mass, pancreatic duct dilatation and parenchymal atrophy are highly suggestive of a ductal adenocarcinoma. Most cystic neoplasms of the pancreas are either microcystic adenomas or mucinous cystic neoplasms. Intraductal papillary mucinous tumors are the uncommon low‐grade malignancy of the pancreatic duct. ICT are rare neoplasms arising from neuroendocrine cells in the pancreas or the periampullary region. ICT are classified as functioning and non‐functioning. The most frequent tumors to metastasize to the pancreas are cancers of the breast, lung, kidney and melanoma. The majority of metastases present as large solitary masses with well‐defined margins.
‘Where the money is’: A case report of the successful removal of a large number of coins by esophagogastroduodenoscopy utilizing a Roth net
Authors: RAYNOR Kathleen M , WU George Y
Published: July 2007

OBJECTIVE:  To demonstrate the use of a Roth net and to determine the maximum number of coins that can be removed per net.

METHODS:  During esophagogastroduodenoscopy, a Roth net was passed multiple times in order to retrieve 49 ingested coins without the use of an over tube.

RESULTS:  Removal of 49 coins of various sizes was accomplished. The largest of the coins was 2.4 cm. Because of damage to the nets during the withdrawal past the gastroesophageal junction, several nets were required. But, there was minimal trauma to the esophageal mucosa and no complications.

CONCLUSIONS:  Removal of ingested foreign objects requires individually tailored treatment. From an extensive literature search, there does not appear to be consensus for standard of care based on the variability of presentation and multiple modalities available for removal.
New protein kinase C activator regulates amyloid precursor protein processing in vitro by increasing α‐secretase activity
Authors: Yang Hong‐Qi , Pan Jing , Ba Mao‐Wen , Sun Zhi‐Kun , Ma Guo‐Zhao , Lu Guo‐Qiang , Xiao Qin , Chen Sheng‐Di
Published: July 2007

The beta amyloid (Aβ) cascade has been at the forefront of the hypothesis used to describe the pathogenesis of Alzheimer's disease (AD). It is generally accepted that drugs that can regulate the processing of the amyloid precursor protein (APP) toward the non‐amyloidogenic pathway may have a therapeutic potential. Previous studies have shown that protein kinase C (PKC) hypofunction has an important role in AD pathophysiology. Therefore, the effects of a new PKC activator, α‐APP modulator [(2S,5S)‐(E,E)‐8‐(5‐(4‐(trifluoromethyl)phenyl)‐2,4‐pentadienoylamino)benzolactam (TPPB)], on APP processing were investigated. Using PC12 cells and SH‐SY5YAPP695 cells, it was found that TPPB promoted the secretion of sAPPα without affecting full‐length expression of APP. The increase in sAPPα by TPPB was blocked by inhibitors of PKC, extracellular signal‐regulated kinase (ERK), c‐Jun N‐terminal kinase (JNK) and tyrosine kinase, suggesting the involvement of these signal transduction pathways. TPPB increased α‐secretase activity [a disintegrin and metalloproteinase (ADAM)10 and 17], as shown by direct fluorescence activity detection and Western blot analysis. TPPB‐induced sAPPα release was blocked by the metalloproteinase inhibitor TAPI‐2, furin inhibitor CMK and by the protein‐trafficking inhibitor brefeldin. The results also showed that TPPB decreased β‐secretase activity, Aβ40 release and beta site APP‐cleaving enzyme 1 (BACE1) expression, but did not significantly affect neprilysin (NEP) and insulin‐degrading enzyme (IDE) expression. Our data indicate that TPPB could direct APP processing towards the non‐amyloidogenic pathway by increasing α‐secretase activity, and suggest its therapeutic potential in AD.
The corticotrophin‐releasing factor‐like peptide urocortin reverses key deficits in two rodent models of Parkinson's disease
Authors: Abuirmeileh Amjad , Lever Rebecca , Kingsbury Ann E. , Lees Andrew J. , Locke Ian C. , Knight Richard A. , Chowdrey Hardial S. , Biggs Christopher S. , Whitton Peter S.
Published: July 2007

The potential neuroprotective action of the corticotrophin‐releasing factor‐related peptide urocortin (UCN) was investigated in the rat 6‐hydroxydopamine (6‐OHDA) and lipopolysaccharide (LPS) paradigms of Parkinson's disease. UCN (20 fmol) was either given at the same time as (T = 0) or 7 days after (T = +7) intracerebral 6‐OHDA or LPS injection. At 14 days after 6‐OHDA or LPS injection, circling behaviour was measured following apomorphine challenge. Circling was significantly lower in rats given UCN at either T = 0 or T = +7 compared with animals given 6‐OHDA or LPS and vehicle. Sham‐treated rats showed no circling. Consistent with these observations, striatal dopamine concentrations were markedly higher in 6‐OHDA/LPS + UCN rats vs. 6‐OHDA/LPS + vehicle groups. Additionally, l‐dihydroxyphenylalanine production by tyrosine hydroxylase was greatly reduced in the striata of 6‐OHDA/LPS + vehicle rats, whereas this was not the case in rats coadministered UCN. Finally, the numbers of tyrosine hydroxylase‐positive cells recorded in the substantia nigra of 6‐OHDA/LPS + vehicle‐treated animals were markedly lower than those of sham‐operated or 6‐OHDA/LPS + UCN rats. Critically, UCN was effective in reversing lesion‐induced deficits when given either at the same time as or 7 days after the neurotoxic insult. To our knowledge, this is the first time that such an effect has been demonstrated in vivo. The apparent ability of UCN to arrest the progression of or even reverse nigral lesions once established suggests that pharmacological manipulation of this system could have substantial therapeutic utility.
mGluR7 inhibits glutamate release through a PKC‐independent decrease in the activity of P/Q‐type Ca2+ channels and by diminishing cAMP in hippocampal nerve terminals
Authors: Martín Ricardo , Torres Magdalena , Sánchez‐Prieto José
Published: July 2007

The modulation of calcium channels by metabotropic glutamate receptors (mGluRs) is a key event in the fine‐tuning of neurotransmitter release. Here we report that, in hippocampal nerve terminals from adult rats, the inhibition of glutamate release by the group III mGluR agonist L‐2‐amino‐4‐phosphonobutyrate (L‐AP4) is largely mediated by mGluR7. In this preparation, P/Q‐type Ca2+ channels support the major component of glutamate release while the remaining release is supported by N‐type Ca2+ channels. The release associated with P/Q channels was modulated by mGluR7, either in the presence of ω‐conotoxin‐GVIA or after decreasing the extracellular Ca2+ concentration [Ca2+]o to abolish the contribution of N‐type Ca2+ channels. Under these conditions, L‐AP4 (1 mm) reduced the evoked glutamate release by 35 ± 2%. This inhibition was largely prevented by pertussis toxin, but it was insensitive to inhibitors of protein kinase C (bisindolylmaleimide) and protein kinase A (H‐89). Furthermore, this inhibition was associated with a reduction in the Ca2+ influx mediated by P/Q channels in the absence of any detectable change in cAMP levels. However, L‐AP4 decreased the levels of cAMP in the presence of forskolin. The activation of this additional signalling pathway was very efficient in counteracting the facilitation of glutamate release induced by forskolin. Thus, mGluR7 mediates the inhibition of glutamate release at hippocampal nerve terminals primarily by inhibiting P/Q‐type Ca2+ channels, although augmenting the levels of cAMP reveals the ability of the receptor to decrease cAMP.
Involvement of NR2A‐ or NR2B‐containingN‐methyl‐d‐aspartate receptors in the potentiation of cortical layer 5 pyramidal neurone inputs depends on the developmental stage
Authors: Le Roux Nicolas , Amar Muriel , Moreau Alexandre , Fossier Philippe
Published: July 2007

In the cortex,N‐methyl‐d‐aspartate receptors (NMDARs) play a critical role in the control of synaptic plasticity processes. We have previously shown in rat visual cortex that the application of a high‐frequency stimulation (HFS) protocol used to induce long‐term potentiation in layer 2/3 leads to a parallel potentiation of excitatory and inhibitory inputs received by cortical layer 5 pyramidal neurones without changing the excitation/inhibition balance of the pyramidal neurone, indicating a homeostatic control of this parameter. We show here that the blockade of NMDARs of the neuronal network prevents the potentiation of excitatory and inhibitory inputs, and this result leaves open to question the role of the NMDAR isoform involved in the induction of long‐term potentiation, which is actually being strongly debated. In postnatal day (P)18–23 rat cortical slices, the blockade of synaptic NR2B‐containing NMDARs prevents the induction of the potentiation induced by the HFS protocol, whereas the blockade of NR2A‐containing NMDARs reduced the potentiation itself. In P29–P32 cortical slices, the specific activation of NR2A‐containing receptors fully ensures the potentiation of excitatory and inhibitory inputs. These results constitute the first report of a functional shift in subunit composition of NMDARs during the critical period (P12–P36), which explains the relative contribution of both NR2B‐ and NR2A‐containing NMDARs in synaptic plasticity processes. These effects of the HFS protocol are mediated by the activation of synaptic NMDARs but our results also indicate that the homeostatic control of the excitation/inhibition balance is independent of NMDAR activation and is due to specialized recurrent interactions between excitatory and inhibitory networks.
Simultaneous feeding by aboveground and belowground herbivores attenuates plant‐mediated attraction of their respective natural enemies
Authors: Rasmann Sergio , Turlings Ted C. J.
Published: July 2007

Herbivore‐damaged plants emit volatile organic compounds that attract natural enemies of the herbivores. This form of indirect plant defence occurs aboveground as well as belowground, but it remains unclear how simultaneous feeding by different herbivores attacking leaves and roots may affect the production of the respective defence signals. We employed a setup that combines trapping of volatile organic signals and simultaneous measurements of the attractiveness of these signals to above and belowground natural enemies. Young maize plants were infested with either the foliar herbivore Spodoptera littoralis, the root herbivore Diabrotica virgifera virgifera, or with both these important pest insects. The parasitic wasp Cotesia marginiventris and the entomopathogenic nematode Heterorhabditis megidis were strongly attracted if their respective host was feeding on a plant, but this attraction was significantly reduced if both herbivores were on a plant. The emission of the principal root attractant was indeed reduced due to double infestation, but this was not evident for the leaf volatiles. The parasitoid showed an ability to learn the differences in odour emissions and increased its response to the odour of a doubly infested plant after experiencing this odour during an encounter with hosts. This first study to measure effects of belowground herbivory on aboveground tritrophic signalling and vice‐versa reemphasizes the important role of plants in bridging interactions between spatially distinct components of the ecosystem.
The ecogenetic link between demography and evolution: can we bridge the gap between theory and data?
Authors: Kokko Hanna , López‐Sepulcre Andrés
Published: July 2007

Calls to understand the links between ecology and evolution have been common for decades. Population dynamics, i.e. the demographic changes in populations, arise from life history decisions of individuals and thus are a product of selection, and selection, on the contrary, can be modified by such dynamical properties of the population as density and stability. It follows that generating predictions and testing them correctly requires considering this ecogenetic feedback loop whenever traits have demographic consequences, mediated via density dependence (or frequency dependence). This is not an easy challenge, and arguably theory has advanced at a greater pace than empirical research. However, theory would benefit from more interaction between related fields, as is evident in the many near‐synonymous names that the ecogenetic loop has attracted. We also list encouraging examples where empiricists have shown feasible ways of addressing the question, ranging from advanced data analysis to experiments and comparative analyses of phylogenetic data.
Metagenomic analysis of the microbial community associated with the coral Porites astreoides
Authors: Wegley Linda , Edwards Robert , Rodriguez‐Brito Beltran , Liu Hong , Rohwer Forest
Published: July 2007

The coral holobiont is a dynamic assemblage of the coral animal, zooxanthellae, endolithic algae and fungi, Bacteria,Archaea and viruses. Zooxanthellae and some Bacteria form relatively stable and species‐specific associations with corals. Other associations are less specific; coral‐associated Archaea differ from those in the water column, but the same archaeal species may be found on different coral species. It has been hypothesized that the coral animal can adapt to differing ecological niches by ‘switching’ its microbial associates. In the case of corals and zooxanthellae, this has been termed adaptive bleaching and it has important implications for carbon cycling within the coral holobiont and ultimately the survival of coral reefs. However, the roles of other components of the coral holobiont are essentially unknown. To better understand these other coral associates, a fractionation procedure was used to separate the microbes, mitochondria and viruses from the coral animal cells and zooxanthellae. The resulting metagenomic DNA was sequenced using pyrosequencing. Fungi, Bacteria and phage were the most commonly identified organisms in the metagenome. Three of the four fungal phyla were represented, including a wide diversity of fungal genes involved in carbon and nitrogen metabolism, suggesting that the endolithic community is more important than previously appreciated. In particular, the data suggested that endolithic fungi could be converting nitrate and nitrite to ammonia, which would enable fixed nitrogen to cycle within the coral holobiont. The most prominent bacterial groups were Proteobacteria (68%), Firmicutes (10%), Cyanobacteria (7%) and Actinobacteria (6%). Functionally, the bacterial community was primarily heterotrophic and included a number of pathways for the degradation of aromatic compounds, the most abundant being the homogentisate pathway. The most abundant phage family was the ssDNA Microphage and most of the eukaryotic viruses were most closely related to those known to infect aquatic organisms. This study provides a metabolic and taxonomic snapshot of microbes associated with the reef‐building coral Porites astreoides and presents a basis for understanding how coral–microbial interactions structure the holobiont and coral reefs.
Exploration of intraclonal adaptation mechanisms of Pseudomonas brassicacearum facing cadmium toxicity
Authors: Pagès Delphine , Sanchez Lisa , Conrod Sandrine , Gidrol Xavier , Fekete Agnes , Schmitt‐Kopplin Philippe , Heulin Thierry , Achouak Wafa
Published: July 2007

Pseudomonas brassicacearum forms phenotypic variants in vitro as well as in planta during root colonization under natural conditions, leading to subpopulations (phase I and II cells) that differ in colony morphology and production of exoenzymes/secondary metabolites. The maximal concentration of cadmium allowing both variants growth was 25 μM; however, phase II cells accumulated fivefold higher Cd than phase I cells, even though both variants showed the same growth rate and kinetics, comprising a long stasis period (50 h). The whole transcriptome analysis of both variants in response to Cd was investigated using the home‐made DNA microarrays. This analysis revealed completely different adaptation mechanisms developed by each variant to withstand and grow in the presence of the toxic. A re‐organization of the cell wall to limit Cd entrance was noticed for phase I cells, as genes encoding levan exopolymers were downregulated at the expense of an upregulation of genes encoding alginate, and an upregulation of transporters such as cadA, and a downregulation of copper transporters. Phase II cells were unable to prevent Cd entrance and recruited genes under the control of oxyR and soxR regulation to face osmotic and oxidant stresses generated by Cd. Putrescine and spermidine metabolism appeared to play a central role in Cd tolerance. Microarray data were validated by biological analyses such as motility, oxidative stress assay, metabolite profiling with ICR‐FT/MS and UPLC, capillary electrophoresis analysis of biogenic amines.
Indications for laparoscopic surgery for Crohn's disease using the Vienna Classification
Authors: Okabayashi K. , Hasegawa H. , Watanabe M. , Nishibori H. , Ishii Y. , Hibi T. , Kitajima M.
Published: July 2007

Objective  The aim of this study was to investigate the clinical outcome of laparoscopic surgery for Crohn's disease and clarify the indications using the Vienna Classification.

Method  Between September 1994 and July 2004, 107 patients with Crohn's disease underwent 124 procedures. Of these, 91 laparoscopic procedures formed the basis of this study. The Vienna Classification, which consists of three subgroups – age at diagnosis (A1‐2), location (L1‐4) and behaviour (B1‐3) – was applied to compare the conversion to open surgery and incidence of postoperative complications.

Results  Conversion to open surgery was necessary in 12 (13.2%) patients. Major and minor postoperative complications occurred in five (5.5%) and 13 (19.8%) patients respectively. The conversion rate, major and total complications in the B3L3/4 subgroup were significantly greater than in the other subgroups. Multivariate analysis showed that B3L3/4 was the only predictive factor for all complications. However, the incidence of major and all complications in the B3L3/4 subgroup did not differ between the open and laparoscopic surgery groups.

Conclusion  Laparoscopic surgery for Crohn's disease is the procedure of choice for all uncomplicated cases (B2L1‐4, B3L1/2). For patients in the complicated group (B3L3/4), laparoscopy is also feasible and justified; however, the surgeon must be aware of the propensity for higher rate of conversion.
Internet information on colorectal cancer: commercialization and lack of quality control
Authors: Sajid M. S. , Iftikhar M. , Monteiro R. S. , Miles A. F. W. , Woods W. G. A. , Baig M. K.
Published: July 2007

Objective  The objective of this study was to evaluate the effectiveness of the internet as a source of information for colorectal cancer (CRC).

Method  Six of the most common search engines (Yahoo, Google, MSN search, Alta Vista, Excite and Lycos) were used for the search of the generic term ‘CRC’. First 300 links were analysed and classified by information type, provider, readership and commercial orientation.

Results  The average time delay was 1.70 s before matches were located. A total of 3.2827 million matches on CRC were found using the six search engines ranging from 700 (Excite) to 1 417 000 (Lycos) websites. Approximately 50% of the links were based on information from textbooks or governmental websites. Commercial companies giving information about private hospitals and products provided over 50% of the websites on CRC. The distribution of target readers was uneven, although a majority of websites were delivering CRC information to public and patients. Readability of information was difficult to comprehend by the public.

Conclusion  The internet is becoming an essential tool for disseminating information about CRC to consumers. Half of the links on CRC are commercially oriented, containing information on goods or private health services. Less than 1% information is being provided by professional societies. To provide relevant CRC information, key consensus criteria for evaluating healthcare‐related websites have to be established. There is an urgent need for CRC information on the internet to be regulated through the establishment of government‐funded organizations (e.g. NHS) or professional societies (e.g. ACPGBI).
Salacia oblonga root decreases cardiac hypertrophy in Zucker diabetic fatty rats: inhibition of cardiac expression of angiotensin II type 1 receptor
Authors: Huang T. H. , He L. , Qin Q. , Yang Q. , Peng G. , Harada M. , Qi Y. , Yamahara J. , Roufogalis B. D. , Li Y.
Published: July 2007

Aims:  We investigated the effect of the water extract of Salacia oblonga (SOE), an ayurvedic antidiabetic and antiobesity medicine, on obesity and diabetes‐associated cardiac hypertrophy and discuss the role of modulation of cardiac angiotensin II type 1 receptor (AT1) expression in the effect.

Methods:  SOE (100 mg/kg) was given orally to male Zucker diabetic fatty (ZDF) rats for 7 weeks. At the end‐point of the treatment, the hearts and left ventricles were weighed, cardiomyocyte cross‐sectional areas were measured, and cardiac gene profiles were analysed. On the other hand, angiotensin II–stimulated embryonic rat heart–derived H9c2 cells and neonatal rat cardiac fibroblasts were pretreated with SOE and one of its prominent components mangiferin (MA), respectively. Atrial natriuretic peptide (ANP) mRNA expression and protein synthesis and [3H]thymidine incorporation were determined.

Results:  SOE‐treated ZDF rats showed less cardiac hypertrophy (decrease in weights of the hearts and left ventricles and reduced cardiomyocyte cross‐sectional areas). SOE treatment suppressed cardiac overexpression of ANP, brain natriuretic peptide (BNP) and AT1 mRNAs and AT1 protein in ZDF rats. SOE (50–100 μg/ml) and MA (25 μmol) suppressed angiotensin II–induced ANP mRNA overexpression and protein synthesis in H9c2 cells. They also inhibited angiotensin II–stimulated [3H]thymidine incorporation by cardiac fibroblasts.

Conclusions:  Our findings demonstrate that SOE decreases cardiac hypertrophy in ZDF rats, at least in part by inhibiting cardiac AT1 overexpression. These studies provide insights into a potential cardioprotective role of a traditional herb, which supports further clinical evaluation in obesity and diabetes‐associated cardiac hypertrophy.
Interpreting clinical trials of diabetic dyslipidaemia: new insights
Authors: Wierzbicki A. S.
Published: July 2007

Current treatment guidelines highlight the importance of aggressive lipid‐modifying therapy in reducing cardiovascular risk in patients with type 2 diabetes. Statins are established as the cornerstone of dyslipidaemia management in diabetic patients, based on their efficacy in lowering levels of low‐density lipoprotein cholesterol (LDL‐C). However, statins fail to address the high residual cardiovascular risk in treated patients, some of which may be attributable to low HDL cholesterol (HDL‐C) and elevated triglycerides and to a preponderance of small, dense LDL particles, indicating the need for further intervention. Fibrates are effective against all components of atherogenic dyslipidaemia associated with type 2 diabetes. Clinical studies, most notably the Fenofibrate Intervention and Event Lowering in Diabetes, indicate that fibrates, most likely in combination with a statin, have a secondary role in reducing cardiovascular risk in patients with type 2 diabetes, particularly in those without prior cardiovascular disease or patients with low HDL‐C. Results are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes trial to fully evaluate the outcome benefits of this combination strategy.
Improved metabolic control by Ipomoea batatas (Caiapo) is associated with increased adiponectin and decreased fibrinogen levels in type 2 diabetic subjects
Authors: Ludvik B. , Hanefeld M. , Pacini G.
Published: July 2007

Aim:  The extract of the white‐skinned sweet potato Ipomoea batatas (Caiapo) has been shown to ameliorate glucose control by improving insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). The present study was designed to further evaluate its mode of action on insulin sensitivity over an extended period of time as well as the effects on fibrinogen and other markers of low‐grade inflammation.

Methods:  In this randomized trial, 27 patients with T2DM on diet only received 4 g of Caiapo daily for 5 months; 34 patients placebo. Before and after therapy, insulin sensitivity [oral glucose insulin sensitivity (OGIS), as glucose clearance from oral glucose tolerance test], parameters of diabetes control, lipids, plasma adiponectin, high‐sensitivity C‐reactive protein (hs‐CRP) and fibrinogen were measured.

Results:  Following Caiapo, we observed an increase in OGIS (293 ± 15 vs. 321 ± 12 ml/m2/min, p = 0.0072) and adiponectin (5.97 ± 0.65 to 6.63 ± 0.70 μg/ml, p = 0.013), while fibrinogen decreased from 3.83 ± 0.16 to 3.64 ± 0.18 mg/ml (p = 0.02). This was associated with an improvement in glycated haemoglobin (HbA1c: 6.46 ± 0.12 vs. 6.25 ± 0.11%, p = 0.008), fasting glucose (138 ± 4 vs. 128 ± 5 mg/dl, p = 0.039) and triglycerides (2.36 ± 0.22 vs. 2.07 ± 0.25 mmol/l, p = 0.032). Body weight, lipid levels and hs‐CRP were not altered. No changes were observed in the placebo group except for HbA1c, which significantly increased from 6.25 ± 0.10 to 6.50 ± 0.12% (p = 0.0001).

Conclusions:  This study confirms the beneficial effects of Caiapo on glucose and HbA1c control in patients with T2DM after 5 months follow‐up. Improvement of insulin sensitivity was accompanied by increased levels of adiponectin and a decrease in fibrinogen. Thus, Caiapo can be considered as natural insulin sensitizer with potential antiatherogenic properties.
Initial treatment with fixed‐dose combination rosiglitazone/glimepiride in patients with previously untreated type 2 diabetes
Authors: Chou H. S. , Palmer J. P. , Jones A. R. , Waterhouse B. , Ferreira‐Cornwell C. , Krebs J. , Goldstein B. J.
Published: July 2007

Aim:  This study assessed the efficacy and safety of two different dosing regimens of fixed‐dose combination (FDC) rosiglitazone (RSG) plus glimepiride (GLIM) compared with RSG or GLIM monotherapy in drug‐naive subjects with type 2 diabetes mellitus (T2DM).

Methods:  Drug‐naive subjects (n = 901) were enrolled into this 28‐week, double‐blind, parallel‐group study if their glycosylated haemoglobin A1c (HbA1c) was >7.5% but ≤12%. Subjects were randomized to receive either GLIM [4 mg once daily (OD) maximal], RSG (8 mg OD maximal) or RSG/GLIM FDC regimen A (4 mg/4 mg OD maximal) or RSG/GLIM FDC regimen B (8 mg/4 mg OD maximal). Patients were assessed for efficacy and safety every 4 weeks for the first 12 weeks of the study, and at weeks 20 and 28. The primary efficacy endpoint was change in HbA1c from baseline. Key secondary endpoints included the proportion of patients achieving recommended HbA1c and fasting plasma glucose (FPG) targets; change from baseline in FPG, insulin, C‐reactive protein (CRP), adiponectin, free fatty acids and lipids; and percentage change in homeostasis model assessment‐estimated insulin sensitivity and β‐cell function. Safety evaluations included adverse‐event (AE) monitoring and clinical laboratory evaluations.

Results:  At week 28, both RSG/GLIM FDC regimens significantly reduced HbA1c (mean ± s.d.: −2.4 ± 1.4% FDC regimen A; −2.5 ± 1.4% FDC regimen B) to a greater extent than RSG (−1.8 ± 1.5%) or GLIM (−1.7 ± 1.4%) monotherapy (model‐adjusted mean treatment difference, p < 0.0001 vs. both RSG and GLIM). Significantly more subjects achieved HbA1c target levels of ≤6.5 and <7% with either RSG/GLIM FDC regimen compared with RSG or GLIM alone (model‐adjusted odds ratio, p < 0.0001 for both comparisons). Similarly, a significantly greater reduction in FPG levels was observed in subjects treated with the RSG/GLIM FDC [mean ± s.d. (mg/dl): −69.5 ± 57.5 FDC regimen A; −79.9 ± 56.8 FDC regimen B) compared with RSG (−56.6 ± 58.1) or GLIM (−42.2 ± 66.1) monotherapy (model‐adjusted mean treatment difference, p < 0.0001 for both comparisons). Improvement in CRP was also observed in subjects who were treated with a RSG/GLIM FDC or RSG monotherapy compared with GLIM monotherapy. RSG/GLIM FDC was generally well tolerated, with no new safety or tolerability issues identified from its monotherapy components, and a similar AE profile was observed across FDC regimens. The most commonly reported AE was hypoglycaemia, and the incidence of confirmed symptomatic hypoglycaemia (3.6–5.5%) was comparable among subjects treated with an RSG/GLIM FDC and GLIM monotherapy.

Conclusions:  Compared with RSG or GLIM monotherapy, the RSG/GLIM FDC improved glycaemic control with no significant increased risk of hypoglycaemia. RSG/GLIM FDC provides an effective and well‐tolerated treatment option for drug‐naive individuals with T2DM.
Towards peakless, reproducible and long‐acting insulins. An assessment of the basal analogues based on isoglycaemic clamp studies
Authors: Heise T. , Pieber T. R.
Published: July 2007

While the advantages of the two basal insulin analogues, glargine and detemir, over neutral protamine Hagedorn are well established, the relative merit of the two compared with each other has been a matter of some controversy. The two analogues are popularly perceived to differ from each other in their pharmacodynamic (PD) profiles, in particular with regard to ‘flatness’ and duration of action. The aim of this review, therefore, is to give a complete overview on the available PD data of both analogues as derived with the glucose clamp technique. In order to improve parity across studies, a common definition for duration of action (time from injection to plasma glucose >8.3 mmol/l) was applied and study data were recalculated when necessary. Despite differences in methodological details, the results of most clamp studies were very consistent. Glargine and detemir both typically show a gentle rise and fall in glucose‐lowering action over time. Duration of action with both analogues is dose dependent, but in the clinically relevant range of 0.35–0.8 U/kg it is close to 24 h in people with type 1 diabetes and in excess of this in people with type 2 diabetes. While both analogues seem to be very similar with regard to the mean shape of their PD profile and duration of action, detemir shows less within‐subject variability in its metabolic effect. These findings in experimental glucose clamp studies are consistent with observations in clinical trials and support routine once daily use with either analogue, in particular in people with type 2 diabetes.
Association between oral antidiabetic use, adverse events and outcomes in patients with type 2 diabetes
Authors: Asche C. V. , McAdam‐Marx C. , Shane‐McWhorter L. , Sheng X. , Plauschinat C. A.
Published: July 2007

Objective:  To quantify adverse events (AEs) associated with the use of metformin (MET), sulphonylureas (SUs) and thiazolidinediones (TZDs) in a usual care setting, and to assess the relationship of AEs to treatment patterns and glycaemic response in patients with type 2 diabetes.

Research design and methods:  An electronic medical record database was used to identify patients with type 2 diabetes age ≥18 years from 1996 to 2005. Patients naïve to oral antidiabetic therapy were followed for 395 days postinitiation of MET, SU or TZD treatment. AEs related to study drugs were evaluated during the follow‐up period. Baseline and follow‐up A1C levels were compared by drug regimen. Associations between the change in A1C, drug regimen changes and AEs were evaluated.

Results:  A total of 14 512 patients (mean age 60.8 years, 52.9% female) were identified. During the follow‐up period, 12.7% of patients experienced an AE (8.6% MET, 15.9% SU and 19.8% TZD patients). SU and TZD patients were more likely to experience an AE than MET (p < 0.001) patients. AEs did not significantly influence A1C outcomes, although MET and SU patients experiencing an AE were more likely to add‐on therapy (odds ratio (OR) = 1.34 and OR = 1.37, respectively; p < 0.05) than those without an AE. MET patients with AEs were more likely to switch therapy (OR = 1.91; p < 0.05) than those without an AE.

Conclusions:  The occurrence of AEs did not significantly impact glycaemic response to therapy. However, AEs may lead to greater treatment switches for patients receiving MET and add‐on therapy for MET‐treated and SU‐treated patients.
Retinopathy in subjects with impaired fasting glucose: the NANSY‐Eye baseline report
Authors: Tyrberg M. , Melander A. , Lövestam‐Adrian M. , Lindblad U.
Published: July 2007

Aims:  Network for Pharmacoepidemiology (NEPI) Antidiabetes Study‐Eye is a randomized placebo‐controlled Swedish trial investigating if treatment with sulphonylurea, in addition to dietary regulation and increased exercise, delays the development of retinopathy in subjects with impaired fasting glucose (IFG).

Methods:  Subjects were surveyed in primary care with repeated fasting blood glucose measurements. Those with a mean of two consecutive values ≥5.6 and <6.1 mmol/l were invited to participate. Baseline physical examination included blood pressure and body mass index (BMI). Fundus photos were taken in two fields using 35‐mm diafilm. The alternative classification of the Wisconsin Epidemiologic Study of Diabetic Retinopathy was used to classify the retinopathy level.

Results:  At baseline, 90 men and 64 women with IFG were photographed. Of these, 16 subjects (10%) had mild or very mild retinopathy. There was no difference in occurrence of retinopathy between subjects with known diagnosis of hypertension or not. However, subjects with retinopathy had significantly higher systolic (154 vs. 141 mmHg, p = 0.013) and diastolic (86 vs. 81 mmHg, p = 0.008) blood pressure levels independent of differences in age, sex and known hypertension. There was a corresponding difference in BMI, being greater in subjects with than in those without retinopathy (32.4 vs. 29.2 kg/m2, p = 0.013). There were no associations between levels of fasting blood glucose or haemoglobin A1c, on the one hand, and retinopathy, on the other.

Conclusion:  Retinopathy may be present even before type 2 diabetes is manifest. It is associated with higher blood pressure levels and higher BMI values, that is, with predominant features of the metabolic syndrome.
Morphology and histology of the male reproductive system of the mangrove land crab Ucides cordatus (L.) (Crustacea, Brachyura, Ocypodidae)
Authors: Castilho G. G. , Ostrensky A. , Pie M. R. , Boeger W. A.
Published: July 2007

Castilho, G. G., Ostrensky, A., Pie, M. R. and Boeger, W. A. 2007. Morphology of the male reproductive system of the mangrove land crab Ucides cordatus (L.) (Crustacea, Brachyura, Ocypodidae) —Acta Zoologica (Stockholm) 88: 000–000

This study provides a detailed description of the macro‐ and microscopic anatomy of the male reproductive system and the spermatogenesis of the mangrove land crab, Ucides cordatus. A total of 64 adult males were collected between December 2002 and February 2005 in mangroves of the Baía de Antonina, State of Paraná, Southern Brazil (25°25′08″S, 48°42′33″W). The reproductive system of this species is composed of the following paired symmetrical structures: testes, vasa deferentia (distal, medial and proximal portions), ejaculatory ducts and penises. During spermatogenesis, which takes place in the testes, the following developmental stages are observed: primary and secondary spermatogonia, primary and secondary spermatocytes, spermatids and spermatozoids. Production of male gametes was continuous throughout the study period, indicating that males of this species are physiologically capable of reproducing all year long.
Phylogeny and taxonomy of endangered South and South‐east Asian freshwater turtles elucidated by mtDNA sequence variation (Testudines: Geoemydidae: Batagur, Callagur, Hardella, Kachuga, Pangshura)
Authors: Praschag P , Hundsdörfer A. K. , Fritz U.
Published: July 2007

Using DNA sequences of the mitochondrial cytochrome b gene, we investigated phylogeny and taxonomy of South and South‐east Asian turtles of all species and subspecies of the genera Batagur, Callagur, Hardella, Kachuga and Pangshura. We found three major clades: (i) a moderately to well‐supported clade containing all large riverine species assigned so far to Batagur, Callagur and Kachuga; (ii) a well‐supported monophylum comprising the four Pangshura species; and (iii) Hardella that could constitute either the sister‐taxon of Pangshura or of a clade comprising Batagur, Callagur, Kachuga and Pangshura. The genus Kachuga is clearly polyphyletic. Therefore, we recommend placing all Batagur, Callagur and Kachuga species in one genus. According to the International Code of Zoological Nomenclature Batagur Gray, 1856, being originally erected at higher rank, takes precedence over the simultaneously published name Kachuga Gray, 1856, and the younger name Callagur Gray, 1870, resulting in an expanded genus Batagur. Indonesian and Malaysian Batagur baska proved to be highly distinct from our sequences of this species from the Sundarbans (Bangladesh, adjacent India), suggesting that a previously unidentified species is involved. This finding is of high conservation relevance in the critically endangered B. baska. The currently recognized subspecies within Hardella thurjii, Pangshura smithii and P. tentoria do not correspond well with mtDNA clades. Considering that the two subspecies of H. thurjii are likely to be based only on individual ontogenetic differences, we propose abandoning the usage of subspecies within H. thurjii. In the Ghaghra River, Uttar Pradesh (India) we detected shared haplotypes in P. smithii and P. tentoria, implying that the unusual morphological characters of the Ghaghra River population of P. tentoria could be the result of interspecific hybridization.
Nail biology and nail science
Authors: De Berker D. A. R. , André J. , Baran R.
Published: July 2007

Synopsis

The nail plate is the permanent product of the nail matrix. Its normal appearance and growth depend on the integrity of several components: the surrounding tissues or perionychium and the bony phalanx that are contributing to the nail apparatus or nail unit.

The nail is inserted proximally in an invagination practically parallel to the upper surface of the skin and laterally in the lateral nail grooves. This pocket‐like invagination has a roof, the proximal nail fold and a floor, the matrix from which the nail is derived.

The germinal matrix forms the bulk of the nail plate. The proximal element forms the superficial third of the nail whereas the distal element provides its inferior two‐thirds.

The ventral surface of the proximal nail fold adheres closely to the nail for a short distance and forms a gradually desquamating tissue, the cuticle, made of the stratum corneum of both the dorsal and the ventral side of the proximal nail fold. The cuticle seals and therefore protects the ungual cul‐de‐sac.

The nail plate is bordered by the proximal nail fold which is continuous with the similarly structured lateral nail fold on each side. The nail bed extends from the lunula to the hyponychium. It presents with parallel longitudinal rete ridges.

This area, by contrast to the matrix has a firm attachment to the nail plate and nail avulsion produces a denudation of the nail bed. Colourless, but translucent, the highly vascular connective tissue containing glomus organs transmits a pink colour through the nail.

Among its multiple functions, the nail provides counterpressure to the pulp that is essential to the tactile sensation involving the fingers and to the prevention of the hypertrophy of the distal wall tissue, produced after nail loss of the great toe nail.
Trend on alternative to animal testing
Authors: Kojima H.
Published: July 2007

For the promotion of 3R's (Reduction, Refinement and Replacement) principles of animal tests, the EU and US established the European Center for the Validation of Alternative Methods (ECVAM) and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), respectively. The purpose of these centers is to detect reliability and relevance of alternative methods, which should be determined by intra‐ and inter‐laboratory validation and peer review for their regulatory acceptance. A similar institute was established in Japan, the Japanese Center for the Validation of Alternative Methods (JaCVAM) in the National Institute of Health Sciences (NIHS). However, there are not enough resources in Japan. It is necessary to cooperate with a Japanese science society like the Japanese Society of Alternatives to Animal Experiments (JSAAE) and a Japanese industry group like the Japanese Cosmetic Industry Association (JCIA). We are expecting JaCVAM to contribute to the validation and peer review of new alternative methods with supporters and international cooperation for the evaluation of the safety of cosmetic ingredients and products.
Stabilization and application of liposomal structures containing sphingomyelin
Authors: Kaise C. , Kaneko T.
Published: July 2007

Cosmetic products with high affinity to the skin have been recently studied, applying liposome and nano‐sized capsules formed by amphiphiles such as lecithin and other lipids to them. Sphingolipid, based on the sphingosine framework among the said lipids, is one of new bio‐lipids which have begun to be studied in terms of physicochemical/biological properties and applicabilities. Sphingomyelin is known as a representative sphingophospholipid. In this study, we tried to use this sphingomyelin as a cosmetic ingredient, particularly for a liposomal formula consisting of the sphingomyelin. As a result, it was found that its barrier (occlusive) ability against water evaporation was superior to that of lecithin as a representative glycerophospholipid, due to a higher rigidity in the bilayer membrane of the liposome. Therefore, it is expected that sphingomyelin will show a complementary effect for damaged intercellular lipid structures of the stratum corneum when it is applied to skin care products. In addition, it was demonstrated that a skin care product with sphingomyelin had a high moisturizing/emollient ability and an improvement effect on existing wrinkles.