bluuebunny/crossref_metadata_2025 huggingface dataset:
Electric fish: new insights into conserved processes of adult tissue regeneration
Authors: Unguez Graciela A.
Published: June 2013

Biology is replete with examples of regeneration, the process that allows animals to replace or repair cells, tissues and organs. As on land, vertebrates in aquatic environments experience the occurrence of injury with varying frequency and to different degrees. Studies demonstrate that ray-finned fishes possess a very high capacity to regenerate different tissues and organs when they are adults. Among fishes that exhibit robust regenerative capacities are the neotropical electric fishes of South America (Teleostei: Gymnotiformes). Specifically, adult gymnotiform electric fishes can regenerate injured brain and spinal cord tissues and restore amputated body parts repeatedly. We have begun to identify some aspects of the cellular and molecular mechanisms of tail regeneration in the weakly electric fish Sternopygus macrurus (long-tailed knifefish) with a focus on regeneration of skeletal muscle and the muscle-derived electric organ. Application of in vivo microinjection techniques and generation of myogenic stem cell markers are beginning to overcome some of the challenges owing to the limitations of working with non-genetic animal models with extensive regenerative capacity. This review highlights some aspects of tail regeneration in S. macrurus and discusses the advantages of using gymnotiform electric fishes to investigate the cellular and molecular mechanisms that produce new cells during regeneration in adult vertebrates.
Mechanisms of muscle gene regulation in the electric organ ofSternopygus macrurus
Authors: Güth Robert , Pinch Matthew , Unguez Graciela A.
Published: June 2013

Animals perform a remarkable diversity of movements through the coordinated mechanical contraction of skeletal muscle. This capacity for a wide range of movements is due to the presence of muscle cells with a very plastic phenotype that display many different biochemical, physiological and morphological properties. What factors influence the maintenance and plasticity of differentiated muscle fibers is a fundamental question in muscle biology. We have exploited the remarkable potential of skeletal muscle cells of the gymnotiform electric fish Sternopygus macrurus to trans-differentiate into electrocytes, the non-contractile electrogenic cells of the electric organ (EO), to investigate the mechanisms that regulate the skeletal muscle phenotype. In S. macrurus, mature electrocytes possess a phenotype that is intermediate between muscle and non-muscle cells. How some genes coding for muscle-specific proteins are downregulated while others are maintained, and novel genes are upregulated, is an intriguing problem in the control of skeletal muscle and EO phenotype. To date, the intracellular and extracellular factors that generate and maintain distinct patterns of gene expression in muscle and EO have not been defined. Expression studies in S. macrurus have started to shed light on the role that transcriptional and post-transcriptional events play in regulating specific muscle protein systems and the muscle phenotype of the EO. In addition, these findings also represent an important step toward identifying mechanisms that affect the maintenance and plasticity of the muscle cell phenotype for the evolution of highly specialized non-contractile tissues.
Sensory flow shaped by active sensing: sensorimotor strategies in electric fish
Authors: Hofmann Volker , Sanguinetti-Scheck Juan I. , Künzel Silke , Geurten Bart , Gómez-Sena Leonel , Engelmann Jacob
Published: June 2013

Goal-directed behavior in most cases is composed of a sequential order of elementary motor patterns shaped by sensorimotor contingencies. The sensory information acquired thus is structured in both space and time. Here we review the role of motion during the generation of sensory flow focusing on how animals actively shape information by behavioral strategies. We use the well-studied examples of vision in insects and echolocation in bats to describe commonalities of sensory-related behavioral strategies across sensory systems, and evaluate what is currently known about comparable active sensing strategies in electroreception of electric fish. In this sensory system the sensors are dispersed across the animal's body and the carrier source emitting energy used for sensing, the electric organ, is moved while the animal moves. Thus ego-motions strongly influence sensory dynamics. We present, for the first time, data of electric flow during natural probing behavior in Gnathonemus petersii (Mormyridae), which provide evidence for this influence. These data reveal a complex interdependency between the physical input to the receptors and the animal's movements, posture and objects in its environment. Although research on spatiotemporal dynamics in electrolocation is still in its infancy, the emerging field of dynamical sensory systems analysis in electric fish is a promising approach to the study of the link between movement and acquisition of sensory information.
Biomimetic and bio-inspired robotics in electric fish research
Authors: Neveln Izaak D. , Bai Yang , Snyder James B. , Solberg James R. , Curet Oscar M. , Lynch Kevin M. , MacIver Malcolm A.
Published: June 2013

Weakly electric knifefish have intrigued both biologists and engineers for decades with their unique electrosensory system and agile swimming mechanics. Study of these fish has resulted in models that illuminate the principles behind their electrosensory system and unique swimming abilities. These models have uncovered the mechanisms by which knifefish generate thrust for swimming forward and backward, hovering, and heaving dorsally using a ventral elongated median fin. Engineered active electrosensory models inspired by electric fish allow for close-range sensing in turbid waters where other sensing modalities fail. Artificial electrosense is capable of aiding navigation, detection and discrimination of objects, and mapping the environment, all tasks for which the fish use electrosense extensively. While robotic ribbon fin and artificial electrosense research has been pursued separately to reduce complications that arise when they are combined, electric fish have succeeded in their ecological niche through close coupling of their sensing and mechanical systems. Future integration of electrosense and ribbon fin technology into a knifefish robot should likewise result in a vehicle capable of navigating complex 3D geometries unreachable with current underwater vehicles, as well as provide insights into how to design mobile robots that integrate high bandwidth sensing with highly responsive multidirectional movement.
Evolution and hormonal regulation of sex differences in the electrocommunication behavior of ghost knifefishes (Apteronotidae)
Authors: Smith G. Troy
Published: June 2013

The ghost knifefishes (family Apteronotidae) are one of the most successful and diverse families of electric fish. Like other weakly electric fish, apteronotids produce electric organ discharges (EODs) that function in electrolocation and communication. This review highlights the diversity in the structure, function and sexual dimorphism of electrocommunication signals within and across apteronotid species. EOD frequency (EODf) and waveform vary as a function of species, sex and/or social rank. Sex differences in EODf are evolutionarily labile; apteronotid species express every pattern of sexual dimorphism in EODf (males>females; males<females; males=females). The direction and magnitude of sex differences in EODf are correlated across species and populations with the responsiveness of EODf to androgens and/or estrogens, which suggests that sex differences evolve through gains and/or losses of hormone sensitivity. During social interactions, apteronotids also modulate their EODs to produce motivational signals known as chirps. Chirp structure differs markedly across species, and many species produce two or more discrete chirp types with potentially different functions. The structure of chirps is sexually dimorphic in all apteronotid species, and chirping is influenced by gonadal steroids and by neuromodulators. Encoding of chirps by the electrosensory system depends on the social context created by the interactions of the EODs of signalers and receivers. Electrosensory systems may thus influence the evolution of signal structure and function, and neuromodulators may coordinately shape the production and reception of electrocommunication signals depending on social context.
Proximate and ultimate causes of signal diversity in the electric fishGymnotus
Authors: Crampton W. G. R. , Rodríguez-Cattáneo A. , Lovejoy N. R. , Caputi A. A.
Published: June 2013

A complete understanding of animal signal evolution necessitates analyses of both the proximate (e.g. anatomical and physiological) mechanisms of signal generation and reception, and the ultimate (i.e. evolutionary) mechanisms underlying adaptation and diversification. Here we summarize the results of a synthetic study of electric diversity in the species-rich neotropical electric fish genus Gymnotus. Our study integrates two research directions. The first examines the proximate causes of diversity in the electric organ discharge (EOD) – which is the carrier of both the communication and electrolocation signal of electric fishes – via descriptions of the intrinsic properties of electrocytes, electrocyte innervation, electric organ anatomy and the neural coordination of the discharge (among other parameters). The second seeks to understand the ultimate causes of signal diversity – via a continent-wide survey of species diversity, species-level phylogenetic reconstructions and field-recorded head-to-tail EOD (ht-EOD) waveforms (a common procedure for characterizing the communication component of electric fish EODs). At the proximate level, a comparative morpho-functional survey of electric organ anatomy and the electromotive force pattern of the EOD for 11 species (representing most major clades) revealed four distinct groups of species, each corresponding to a discrete area of the phylogeny of the genus and to a distinct type of ht-EOD waveform. At the ultimate level, our analyses (which emphasize the ht-EOD) allowed us to conclude that selective forces from the abiotic environment have had minimal impact on the communication component of the EOD. In contrast, selective forces of a biotic nature – imposed by electroreceptive predators, reproductive interference from heterospecific congeners, and sexual selection – may be important sources of diversifying selection on Gymnotus signals.
Environmental enrichment does not impact on tumor growth in mice
Authors: Westwood Jennifer A , Darcy Phillip K , Kershaw Michael H
Published: June 2013

The effect of environmental enrichment (EE) on a variety of physiologic and disease processes has been studied in laboratory mice. During EE, a large group of mice are housed in larger cages than the standard cage and are given toys and equipment, enabling more social contact, and providing a greater surface area per mouse, and a more stimulating environment. Studies have been performed into the effect of EE on neurogenesis, brain injury, cognitive capacity, memory, learning, neuronal pathways, diseases such as Alzheimer’s, anxiety, social defeat, emotionality, depression, drug addiction, alopecia, and stereotypies. In the cancer field, three papers have reported effects on mice injected with tumors and housed in enriched environments compared with those housed in standard conditions. One paper reported a significant decrease in tumor growth in mice in EE housing. We attempted to replicate this finding in our animal facility, because the implications of repeating this finding would have profound implications for how we house all our mice in our studies on cancer. We were unable to reproduce the results in the paper in which B16F10 subcutaneous tumors of mice housed in EE conditions were smaller than those of mice housed in standard conditions. The differences in results could have been due to the different growth rate of the B16F10 cultures from the different laboratories, the microbiota of the mice housed in the two animal facilities, variations in noise and handling between the two facilities, food composition, the chemical composition of the cages or the detergents used for cleaning, or a variety of other reasons. EE alone does not appear to consistently result in decreased tumor growth, but other factors would appear to be able to counteract or inhibit the effects of EE on cancer progression.
The effect of mobile phase composition on separation of some Non-Steroidal Anti-Inflammatory Drugs of the 2-arylpropanoic acid derivatives in System of Reversed-Phase Pressurized Planar Electrochromatography and High-Performance Thin-Layer Chromatography
Authors: Kopciał Ewelina , Polak Beata , Pietraś Rafał , Dzido Tadeusz H.
Published: June 2013

Separation of some Non-Steroidal Anti-Inflammatory Drugs, 2-arylpropanoic acid derivatives (naproxen, ketoprofen, fenbufen, indoprofen, fenprofen, flurbiprofen, ketorolac, carprofen) has been investigated with pressurized planar electrochromatography (PPEC) and high-performance thin-layer chromatography (HPTLC) in reversed-phase system.The mobile phase consisted of acetonitrile, and aqueous buffer. The influence of concentration of organic modifier in the mobile phase and the mobile phase buffer pH on migration distance (PPEC) and retardation factor (HPTLC) has been investigated and compared.
Radiolabeling and biodistribution of new acetylcholinesterase inhibitor – 6-Hydrazino-N-[5-(2,3-dihydro-1H-cyclopenta[b]quinolin-9-ylamino)pentyl]nicotinamide hydrochloride
Authors: Szymański Paweł , Laznickova Alice , Laznicek Milan , Markowicz Magdalena , Mikiciuk-Olasik Elżbieta
Published: June 2013

Nowadays research concerning new strategies for earlier diagnosis is among the most active areas in Alzheimer's science. Brain imaging techniques are among the most promising areas of research focused on early detection of Alzheimer’s disease (AD). In the present study we describe radiolabeling of a novel acetylcholinesterase inhibitor 6-hydrazino-N-[5-(2,3-dihydro-1H-cyclopenta[b]quinolin-9-ylamino)pentyl]nicotinamide (5C-5) with 99m-Technetium (99mTc). Biodistribution study of compound 5C-5 radiolabeled with 99mTc after intravenous administration to rats was also performed. According to biodistribution study 99mTc-radioactivity was mainly localized in the liver, partly also in the kidney, lung and gastrointestinal tract. Furthermore, compound under study revealed comparatively rapid blood radioactivity clearance.
Validation of densitometric and videodensitometric TLC methods for analysis of vigabatrin in pharmaceutical formulations
Authors: Paw Beata
Published: June 2013

Two new, simple, precise and accurate thin-layer chromatography methods with densitometric and videodensitometric detection were developed for the determination of vigabatrin in pharmaceutical preparations. The analysis was performed on silica gel 60 F254 plates in horizontal chambers with acetone-butan-2-one-formic acid-water (40:45:5:10, v/v), as mobile phase. The method is based on the reaction of the primary amino group of vigabatrin with ninhydrin reagent producing a colored product which absorbs maximally at 483 nm. Videodensitometric assay was performed at visible light. Calibration plots were constructed in the range 2.0 - 20.0 µg/spot with good correlation coefficients r=0.9991 and r=0.9949 for densitometry and videodensitometry, respectively. The LOD was 0.6 µg and 0.8 µg per spot for densitometric and videodensitometric assay, respectively; the LOQ was 1.5 µg per spot for both methods. The active substance was extracted from tablets with methanol. The mean ± SD recovery from commercially available tablets was 100.22 ± 0.61 % (n=6) for the both methods. Tablet excipients did not interfere with the chromatography. Finally, the methods were compared statistically in respect of precision and accuracy. No significant differences were observed.
The stability of cefoselis sulfate in aqueous solutions in accordance with the ICH guidelines for stability testing
Authors: Zalewski Przemysław , Cielecka-Piontek Judyta , Jelińska Anna , Marczak Paulina
Published: June 2013

The stability of cefoselis sulfate in accordance with the ICH Guidelines for the Stability Testing for Medicinal Substances and Pharmaceutical Products was investigated. The study was conducted at different pH, temperature, oxidative factor and with a varying exposure time. The tests of photostability were also done. Changes in cefoselis sulfate concentration were followed using the HPLC method with UV detection. Cefoselis sulfate was classified depending on the stress conditions applied and data obtained in the study as extremely labile in base pH, very labile in neutral pH, labile in acidic pH and in the presence of an oxidative factor. In the photostability test cefoselis sulfate was classified as photolabile.
Qualitative and quantitative analysis of diosgenin in pure substance by TLC-densitometry
Authors: Dołowy Małgorzata
Published: June 2013

A simple and sensitive TLC-densitometric method for qualitative and quantitative analysis of diosgenin in pure sample was elaborated. Satisfactory results of the densitometric analysis of examined compound was obtained using chloroform-acetone in volume composition 40:10 (v/v) as a mobile phase and by means of the chromatographic plates precoated with silica gel 60F254 and silica gel 60. Visualization of the diosgenin spots was achieved by dipping the plates into 10% ethanol solution of phosphomolybdic acid and 10% ethanol solution of sulfuric acid respectively. The limit of detection (LOD) and the limit of quantification (LOQ) of diosgenin investigated under different chromatographic conditions was determined. The results obtained in this work indicate that, the elaborated method is suitable for densitometric analysis of diosgenin but only in pure sample.
Theoretical and experimental analytical studies on potassium clavulanate
Authors: Cielecka-Piontek Judyta , Paczkowska Magdalena , Zalewski Przemysław , Krause Anna , Bernard Ireneusz , Mania Aleksandra , Lewandowska Kornelia , Barszcz Bolesław
Published: June 2013

The spectral and chromatographic procedures (FT-IR, D-UV, TLC, DSC, HPLC-DAD) were developed as alternative tools, to these which are recommended by pharmacopeial guidelines, for identification of potassium clavulanate. As a support for the studies quantum chemical calculations based on the density functional theory (DFT) were used. For a determination of potassium clavulanate in the presence of degradation products two analytical methods were determined: HPLC-DAD and derivative spectroscopy. In the HPLC-DAD method, C-18 stationary phase and 12 mM ammonium acetate-acetonitrile (96:4 V/V) were used. A quantitative determination of potassium clavulanate was carried out by using PDA detector at 220 nm, with a flow rate of 1.0 mL min-1. In derivative spectroscopy the change of values of amplitudes of potassium clavulanate and the first-derivative absorption spectra were used (λ=228 nm) for its determination.
Mandibular odontogenic cysts. Individual cases description and literature review
Authors: Rahnama Mansur , Szczerba Joanna , Hamwi Rozan
Published: June 2013

According to definition, a cyst is a unilocular or multilocular pathological cavity within bones or soft tissues, filled with liquid. The true tissue is distinct from the false one, beside the connective tissue capsule on the periphery, through the presence of epithelial liner. Oral cavity and maxillary bones, due to the presence of numerous epithelial structures of developmental nature, are the area of frequent cystic changes. The aim of the study was to present the actual state of knowledge concerning etiology, pathogenesis, morphology, treatment and methods applying to the reconstruction of bone defects after the enucleation of odontogenic cysts in the mandible as well as to introduce the description of three individual cases. In cases concerning three patients, the bone substitute material Calc-i-oss combined with PRP was applied after the surgical procedure consisting in an enucleation of the mandibular odontogenic cyst. The observation of the healing process concerning the postoperative wound was carried out after 7 days from the procedure. In two cases, the check radiograph was taken 6 months after the surgical intervention. In all cases, the proper healing of the postoperative wound was observed during the medical check-up after the procedure. The radiological image taken 6 months after the surgical intervention proved the regeneration of the bone texture. Methods of treatment concerning the bone defects after the enucleation of odontogenic cysts constitute a topic, which is still valid. The described cases of the bone defects in the mandible filled with Calc-i-oss material combined with PRP (platelet rich plasma) give good healing results.
Osteocalcin and selected biochemical parameters of bone turnover in healthy subjects
Authors: Wojtysiak-Duma Beata , Malecha-Jędraszek Arleta , Duma Dariusz , Burska Agata , Korpysz Maciej , Donica Helena
Published: June 2013

Osteocalcin (OC) is non-collagenous bone matrix protein produced by osteoblasts. OC binds to hydroxyapatite and is deposited in the bone matrix. Concentration of OC in the blood seems to reflect both osteogenesis and increased bone metabolism and depends on age, sex, menopausal status. The aim of our study was to evaluate changes in the concentration of osteocalcin and selected biochemical parameters of bone turnover in different stages of life in healthy people. We found that the mean serum levels of OC were significantly greater in women than in men. The highest OC levels were found in men under the age of 30 with a decrease in the fourth decade of life. In the group of women of up to 40 years of age, OC concentrations were comparable with the equivalent group of men. The lowest concentration of OC was found in the age group 40-49, with the significant increase in the subsequent decades of life. In both men and women, we found a significant correlation of OC with the calcium concentrations and alkaline phosphatase activity. Osteocalcin determinationa, particulary in women, may be useful laboratory parameters of osteoporosis process.
Optimization of Cationic Corn Starch Production by Using Response Surface Methodology
Authors: Shin Hae-hun , Cho Seok-Cheol
Published: June 2013

Cationic starch is widely used in the paper-making process as a wet-end additive to improve sheet strength and to provide better retention of fines as well as fillers. Cationic corn starch is generally used in most grades of paper because of its cheapness and opulency. Low-substituted cationic starch which has a degree of substitution (DS) of below 0.03 is widely used but regulations pertaining to the total amount of lead present in anionic waste have made paper companies leery about its continued use. As a result, the need for a high-substituted cationic starch which has a DS above 0.04 has been growing. On the basis of the results of the alkali gelatinization initiation concentration (AGIC) of corn starch suspension, the optimization of corn starch cationization was performed by response surface methodology (RSM). When 8% (w/w) cationic reagent was added to the starch suspension with 1.89% (w/w) of Na2SO4 and NaOH, after which 6.75 meq/g-starch of AGIC was added at 38.48°C. It appears that cationic starch can be produced with a reaction yield of 67.28% (DS 0.0302) over the course of 18 h. If the cationic reagent is increased to 20% (w/w), more than 24 h was needed to reach the maximum reaction yield. Within 24 h, the optimized cationization process produced cationic corn starch which has a DS of 0.064.
Nonthermal Pasteurization of Takju using Batch High Voltage Pulsed Electric Fields with Exponential Decay Pulse
Authors: Kim Bo-Ra , Chung Tae-Bum , Hong Hee Joung , Kim Jin-Seon , Shin Jung-Kue
Published: June 2013

Makgeolli, a traditional Korean turbid rice wine, was treated with pulsed electric fields (PEF) for the purpose of a development of a new cold pasteurization processes. Inactivation of yeast in the makgeolli increased with increase in intensity of the electric field strength and treatment time. The initial yeast count of the makgeolli was 2×108 cfu/ ml. A reduction of 2D was obtained at 30 kV/cm and 256 exponential decay pulses at room temperature. The combination of PEF and conventional thermal treatment inactivated the yeast more effectively. Reductions of up to 8D were observed when the makgeolli was treated with PEF of 20 kV/cm and 256 pulses at 50°C. The inactivation of the yeast in makgeolli increased with an increase in alcohol content. When the alcohol content of the makgeolli increased to 12%, PEF treatment with 30 kV/cm and 256 pulses resulted in a 4.8D reduction of yeast. No changes in pH, acidity, or the growth of yeast were observed in the PEF treated makgeolli during storage at 4°C for 4 weeks.
Chemical Leachates from Food Contact Packaging Materials and Health Risks
Authors: Puligundla Pradeep , Ko Sanghoon
Published: June 2013

Food contact packaging material should be stable and non-reactive with the food that it is in contact with, and must promote the safety of food. However, for a number of years, there has been evidence that indefinitely small amounts of chemicals could migrate or leach from food packaging materials into the foods they hold. The chemistry and toxicity of such leachates are well-known and documented; and there is a growing concern over the matter among the general public. In addition, food regulatory agencies are imposing more stringent regulations on the maximum allowable amounts of known leachates into foods in recent years. The majority of toxicity studies have revealed that trace amounts of leachates pose no immediate health problems in humans. However, studies on the effects of long-term exposure or synergistic/cumulative toxicity are still lacking. The present review provides an overview of the chemical nature and toxicity of certain leachates from various types of food contact packaging materials that are in wide use.
Modeling Charge Transport and Dynamics in Biomolecular Systems
Authors: Gutierrez R. , Cuniberti G.
Published: June 2013

Charge transport at the molecular scale builds the cornerstone of molecularelectronics (ME), a novel paradigm aiming at the realization of nanoscaleelectronics via tailored molecular functionalities. Biomolecular electronics,lying at the borderline between physics, chemistry and biology, can be con-sidered as a sub-field of ME. In particular, the potential applications of DNAoligomers either as template or as active device element in ME have stronglydrawn the attention of both experimentalist and theoreticians in the past years.While exploiting the self-assembling and self-recognition properties of DNAbased molecular systems is meanwhile a well-established field, the poten-tial of such biomolecules as active devices is much less clear mainly due tothe poorly understood charge conduction mechanisms. One key componentin any theoretical description of charge migration in biomolecular systems,and hence in DNA oligomers, is the inclusion of conformational fluctuationsand their coupling to the transport process. The treatment of such a problemaffords to consider dynamical effects in a non-perturbative way in contrastto, e.g., conventional bulk materials. Here we present an overview of recentwork aiming at combining molecular dynamic simulations and electronicstructure calculations with charge transport in coarse-grained effective model Hamiltonians. This hybrid methodology provides a common theoretical start-ing point to treat charge transfer/transport in strongly structurally fluctuatingmolecular-scale physical systems.
Mirabegron: β3-Adrenergic Receptor Agonist for the Treatment of Overactive Bladder
Authors: Bridgeman Mary Barna , Friia Nicholas J , Taft Christina , Shah Milisha
Published: June 2013

OBJECTIVE

To review the place in therapy of mirabegron, a new oral β3-adrenergic receptor agonist, for the treatment of overactive bladder (OAB).

DATA SOURCES

A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996-April 2013) was conducted using the key words mirabegron, receptor, adrenergic, beta-3; adrenergic beta-3 receptor; beta-3 receptor, and overactive bladder; urinary bladder; overactive. All published articles regarding mirabegron were included. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed.

STUDY SELECTION AND DATA EXTRACTION

Available English-language data from reviews, abstracts, presentations, and clinical trials of mirabegron in humans were reviewed; relevant clinical data were selected and included.

DATA SYNTHESIS

Mirabegron is the newest option for treatment of OAB with symptoms of urge incontinence. As a β3-receptor agonist, it reduces bladder muscle contractions. In two 12-week, randomized, double-blind, placebo-controlled Phase 3 studies, mirabegron significantly reduced the number of incontinence episodes per 24 hours from baseline (−1.47, −1.63, and −1.13; p < 0.05; and −1.57, −1.46, and −1.17; p < 0.05; all values for mirabegron 50 mg, 100 mg, and placebo). Micturitions per 24 hours were also reduced from baseline (−1.66, −1.75, and −1.05; p < 0.05; and −1.93, −1.77, and −1.34; p < 0.05; all values for mirabegron 50 mg, 100 mg, and placebo). A 12-month trial found mirabegron to have a safety and efficacy profile similar to that of tolterodine.

CONCLUSIONS

Treatment of OAB initially includes lifestyle and nonpharmacologic intervention; for patients with persistent symptoms despite these treatments, drug therapy represents a next-step approach for symptom control. Mirabegron alleviates symptoms of OAB while having a mechanism of action that provides an alternative for patients who are intolerant of or who have contraindications to anticholinergic agents. The place in therapy of mirabegron relative to anticholinergics in the treatment of urge incontinence has not yet been established.
Reintroduction of Clozapine After Perforation of the Large Intestine—A Case Report and Review of the Literature
Authors: Ikai Saeko , Suzuki Takefumi , Uchida Hiroyuki , Mimura Masaru , Fujii Yasuo
Published: June 2013

OBJECTIVE

To report on a patient who was successfully rechallenged with clozapine after perforation of the large intestine and pulmonary embolism postoperatively, and provide a literature review on clozapine rechallenge.

CASE SUMMARY

A 46-year-old Japanese man with treatment-resistant schizophrenia developed constipation and slight abdominal discomfort while taking clozapine 275 mg/day. He developed appendicitis, leading to perforation of the large intestine. During the postsurgery period, a partial embolism of the pulmonary artery was revealed. The patient's constipation was relieved when clozapine was discontinued, but other antipsychotics failed to control his delusions well. After thorough discussion, it was decided to rechallenge with clozapine. The low dose of clozapine 200 mg/day was tolerable for his delusion, and his constipation was managed with laxatives and exercises until 8 months after the accident.

DISCUSSION

Clozapine is a gold standard medication in treatment-resistant schizophrenia but is associated with various adverse effects, some of which are life-threatening. Reintroduction of clozapine after severe adverse drug effects when other medications are not effective almost always poses a clinical dilemma for mental health professionals. A PubMed search (to January 25, 2013) using the key words clozapine and rechallenge found 50 articles. There were only sporadic positive case reports regarding the rechallenge after clozapine-related serious gastrointestinal problems.

CONCLUSIONS

From the currently available evidence, most psychiatrists appear to avoid reintroduction of clozapine. However, the evidence is too weak to draw a definitive conclusion about reintroduction of this drug. Reintroduction of clozapine after initial adverse effects in patients with treatment-resistant schizophrenia may warrant case-by-case judgment, but needs to be further investigated.
Functional Range of Creatinine Clearance for Renal Drug Dosing: A Practical Solution to the Controversy of Which Weight to Use in the Cockcroft-Gault Equation
Authors: Brown Daniel L , Masselink Andrew J , Lalla Christina D
Published: June 2013

OBJECTIVE

To describe a practical solution for addressing body weight when using the Cockcroft-Gault equation to determine drug dosing.

DATA SOURCES

A literature search was conducted using PubMed MEDLINE (1980-April 2013) using creatinine clearance, Cockcroft and Gault, Cockcroft-Gault, body weight, and obesity as search terms. Reference citations from publications reviewed were included.

STUDY SELECTION AND DATA EXTRACTION

All English-language articles identified by the search were reviewed. Studies comparing the accuracy and bias of the Cockcroft-Gault equation using a variety of body weight designations in adult populations were included in the analysis.

DATA SYNTHESIS

Study results indicated that, for obese patients, ideal body weight (IBW) underestimates creatinine clearance (CrCl) and total body weight (TBW) overestimates CrCl. Some studies suggest that adjusted body weight with a factor of 0.4 is most accurate, while others suggest the use of lean body weight. These studies have failed to produce a definitive resolution to the controversy. Despite many well-designed studies, the Cockcroft-Gault body weight controversy remains unresolved and uncertainty continues to exist as to which form of weight should be used in the equation. A different perspective is warranted. Since renal dosing guidelines are generally based on ranges of CrCl, applying a CrCl range to describe a patient's renal function might be more practical than relying on a specific CrCl value. Ultimately, CrCl-based drug dosing involves the use of an imperfect mathematical approximation, which is then applied as precisely as possible to the benefit versus risk analysis for a specific patient.

CONCLUSIONS

We propose the use of a CrCl range for drug dosing purposes, with the lower boundary defined by using IBW in the Cockcroft-Gault equation and the upper boundary by using TBW.
Reduced Sulfation of Chondroitin Sulfate but Not Heparan Sulfate in Kidneys of Diabetic db/db Mice
Authors: Reine Trine M. , Grøndahl Frøy , Jenssen Trond G. , Hadler-Olsen Elin , Prydz Kristian , Kolset Svein O.
Published: June 2013

Heparan sulfate proteoglycans are hypothesized to contribute to the filtration barrier in kidney glomeruli and the glycocalyx of endothelial cells. To investigate potential changes in proteoglycans in diabetic kidney, we isolated glycosaminoglycans from kidney cortex from healthy db/+ and diabetic db/db mice. Disaccharide analysis of chondroitin sulfate revealed a significant decrease in the 4-O-sulfated disaccharides (D0a4) from 65% to 40%, whereas 6-O-sulfated disaccharides (D0a6) were reduced from 11% to 6%, with a corresponding increase in unsulfated disaccharides. In contrast, no structural differences were observed in heparan sulfate. Furthermore, no difference was found in the molar amount of glycosaminoglycans, or in the ratio of hyaluronan/heparan sulfate/chondroitin sulfate. Immunohistochemical staining for the heparan sulfate proteoglycan perlecan was similar in both types of material but reduced staining of 4-O-sulfated chondroitin and dermatan was observed in kidney sections from diabetic mice. In support of this, using qRT-PCR, a 53.5% decrease in the expression level of Chst-11 (chondroitin 4-O sulfotransferase) was demonstrated in diabetic kidney. These results suggest that changes in the sulfation of chondroitin need to be addressed in future studies on proteoglycans and kidney function in diabetes.
Pathophysiological Implications of Fibroblast Growth Factor-23 and Klotho and Their Potential Role as Clinical Biomarkers
Authors: Donate-Correa Javier , Muros de Fuentes Mercedes , Mora-Fernández Carmen , Navarro-González Juan F
Published: June 2013

BACKGROUND

Fibroblast growth factor-23 (FGF-23) and Klotho constitute the main regulatory system of phosphorus homeostasis. Beyond this physiological role, there is growing evidence suggesting that this system has relevant pathophysiological implications in different clinical processes.

CONTENT

In this review we discuss the pathophysiological implications of the FGF-23/Klotho system and the potential utility that measurements of its components may have as clinical biomarkers in different clinical settings, such as progression of chronic kidney disease, acute renal failure, and secondary hyperparathyroidism, as well as vascular dysfunction, atherosclerosis, and cardiovascular morbidity and mortality. We outline and discuss the current commercially available assays for determination of FGF-23 and Klotho and the assay limitations that must be overcome to translate these biomarkers into reliable indicators in clinical practice.

In addition to its physiological role, the FGF-23/Klotho system appears to provide important information regarding the pathophysiology of several clinical conditions. Although there has been increasing study of the components of this new biological system and their potential use as clinical biomarkers, the ultimate value of this system in clinical practice will not be known until remaining assay limitations can be overcome and adequately designed studies have been conducted to demonstrate its clinical utility.
Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats
Authors: Shan C Y , Yang J H , Kong Y , Wang X Y , Zheng M Y , Xu Y G , Wang Y , Ren H Z , Chang B C , Chen L M
Published: June 2013

For centuries, Berberine has been used in the treatment of enteritis in China, and it is also known to have anti-hyperglycemic effects in type 2 diabetic patients. However, as Berberine is insoluble and rarely absorbed in gastrointestinal tract, the mechanism by which it works is unclear. We hypothesized that it may act locally by ameliorating intestinal barrier abnormalities and endotoxemia. A high-fat diet combined with low-dose streptozotocin was used to induce type 2 diabetes in male Sprague Dawley rats. Berberine (100 mg/kg) was administered by lavage to diabetic rats for 2 weeks and saline was given to controls. Hyperinsulinemia and insulin resistance improved in the Berberine group, although there was no significant decrease in blood glucose. Berberine treatment also led to a notable restoration of intestinal villi/mucosa structure and less infiltration of inflammatory cells, along with a decrease in plasma lipopolysaccharide (LPS) level. Tight junction protein zonula occludens 1 (ZO1) was also decreased in diabetic rats but was restored by Berberine treatment. Glutamine-induced glucagon-like peptide 2 (GLP2) secretion from ileal tissue decreased dramatically in the diabetic group but was restored by Berberine treatment. Fasting insulin, insulin resistance index, plasma LPS level, and ZO1 expression were significantly correlated with GLP2 level. In type 2 diabetic rats, Berberine treatment not only augments GLP2 secretion and improves diabetes but is also effective in repairing the damaged intestinal mucosa, restoring intestinal permeability, and improving endotoxemia. Whether these effects are mechanistically related will require further studies, but they certainly support the hypothesis that Berberine acts via modulation of intestinal function.
Attempts using cryotherapy to achieve more rapid healing in patients with cutaneous leishmaniasis due to L. braziliensis braziliensis
Authors: Cuentas Elmer Alejandro Llanos , Marsden Philip Davis , Torre Douglas , Barreto Air Colombo
Published: June 2013

The use of cryotherapy as an adjunct to systemic antimonial therapy (Clucantime) was studied in 17 patients with a total of23 skin lesions of leishmaniasis in an area where L. braziliensis braziliensis is the species in circulation. Cryotherapy did not speed healing and has been discarded as an auxiliary therapeutic measure in our practice. However this technique may be suitable for species o/Leishmania causing more limited superficial lesions in man without the danger of metastasis.
Comparação entre praziquantel e oxamniquine no tratamento da esquistossomose mansoni
Authors: Emanuel Antônio , Prata Aluízio
Published: June 2013

Tratamos 120 pacientes masculinos com idade de 17 a 19 anos, portadores de esquistossomose mansoni nas formas intestinal e hepatointestinal, pareados de acordo com o número de ovos por grama de fezes. Um membro de cada par tomou oxamniquine na dose de 15mg/kg e o outro, praziquantel na dose de 55mg/kg, em cápsulas. Dos 106 pacientes avaliados com pelo menos dois exames de fezes, negativaram-se 44 (83%) dos que tomaram praziquantel e 41 (77,3%) dos que tomaram oxamniquine. Ambas as drogas foram relativamente bem toleradas, com ligeira vantagem da oxamniquine.
Estudo sobre o diagnóstico da giardíase por meio do método Kato-Katz
Authors: Castilho Vera Lucia Pagliusi , Guizelini Elaine , Turri Eliana Salgado , Amato Neto Vicente , Campos Rubens , Moreira Antonio Augusto Baillot , Pinto Pedro Luiz Silva
Published: June 2013

Foi verificado que é possível diagnosticar a giardíase através de exame de fezes realizado pelo método de Kato-Katz, hoje bastante utilizado no Brasil. Todavia, para reconhecimento da protozoose em questão, a eficácia do processo da centrífugo-fiutuação em sulfato de zinco mostrou-se maior. As sensibilidades das técnicas de Kato-Katz e da sedimentação espontânea em água foram equiparáveis, afigurando-se mais produtivas, a propósito do emprego da primeira, as análises efetuadas imediatamente ou após 24 horas em relação à ocasião do preparo.
Metabolismo do ácido fólico na malária
Authors: Pinto Aymoré Vaz , Paiva Mércia Cardoso , Milfont Marina Dantas Alencar , Chiarini Lucia , Ferreira Cristina Maria de Lemos , Prata Aluizio , Santos João Barberino , Santos Fernando Alexandrino Alves dos
Published: June 2013

O estudo de 27 pacientes infectados pelo Plasmodium falciparum comparado com pessoas aparentemente sadias mostra: a) diminuição do folato no soro dos pacientes infectados; b) diminuição do folato sêrico nos primeiros 8 dias que seguiram ao tratamento, interpretados como sendo devido à mobilização pela eritropoiese compensadora; c) folato eritrocítico normal.
Hepatite fulminante e febre negra de Lábrea: estudo de 5 casos procedentes de Codajás, Amazonas, Brasil
Authors: Fonseca José Carlos Ferraz da , Ferreira Luiz Carlos Lima , Guerra Ana Luiza Pereira da Silva , Passos Leni Mota , Simonetti José Pascoal
Published: June 2013

São descritas as manifestações clinicas, laboratoriais e aspectos evolutivos de cinco pacientes procedentes de Codajás-Amazonas, atendidos no Instituto de Medicina Tropical de Manaus devido ao quadro de hepatopatia grave, com período médio de doença de quatro dias. Quatro destes pacientes evoluiram para óbito, com uma média de cinco dias desde o inicio dos pródromos. A sorologia para hepatite B mostrou que o Ag HBs estava presente em quatro e o Anti - HBc em todos. Dos pacientes que foram ao óbito, através da necropsia a histopatologia do fígado revelou quadro de hepatite fulminante em dois e de febre de Lábrea nos outros dois.
Tipos de colágeno nas áreas de fibrose da cardiopatia chagásica crônica com lesão vorticilar esquerda e insuficiência cardíaca
Authors: Raso Pedro , Toppa Nivaldo Hartung
Published: June 2013

Foi feita a identificação dos tipos de colágeno em cortes histológicos de fragmentos de 15 corações de indivíduos portadores de doença de Chagas crônica com lesão vorticilar esquerda e ICC. As preparações coradas pelo Sirius Supra Red F3BA, preconizada por Junqueira e cols e examinadas em microscópio de polarização (Leitz) revelaram colágeno de tipo I e III nas zonas de fibrose. As primeiras preponderaram nos dois terços externos da região vorticilar, nas áreas de fibrose endomisial e perimisial do miocárdio sem ou com escasso infiltrado inflamatório e na região subendocárdica dos músculos papilares. O tipo III foi mais freqüente no terço interno da região vorticilar, no endocárdio da parede ventricular, em certas áreas do miocárdio onde a inflamação ainda estava em atividade e nas porções mais centrais dos músculos papilares. Os AA fazem um breve comentário sobre o possível mecanismo patogenético da fibrose na doença de Chagas.
Tipos de colágeno na fibrose hepática esquistossomótica de Symmers
Authors: Raso Pedro , Toppa Nivaldo Hartung , Oliveira Dionne M. , Lemos Francira P.
Published: June 2013

Os AA. estudaram o tipo de colágeno em cortes histológicos de fragmentos de fígado de 12 indivíduos portadores da forma hepatesplênica da esquistossomose mansoni, pela técnica de coloração pelo Sirius Supra Red F3BA. Como controle usaram cortes histológicos de 12 fragmentos de fígado de indivíduos sem doenças fibrosantes. As preparações coradas pelo Sirius Supra Red F3BA e examinadas em microscópio de polarização (Leitz) revelaram que a fibrose periportal é constituída por colágeno de tipos I e III, com predominância do primeiro.
Involvement of the autonomic nervous system in Chagas heart disease
Authors: Lopes Edison Reis , Tafuri Washington Luiz
Published: June 2013

The autonomic nervous system and especially the intracardiac autonomic nervous system is involved in Chagas' disease. Ganglionitis and periganglionitis were noted in three groups ofpatients dying with Chagas'disease: 1) Those in heart failure; 2) Those dying a sudden, non violent death and; 3) Those dying as a consequence ofaccidents or homicide. Hearts in the threegroups also revealed myocarditis and scattered involvement of intramyocardial ganglion cells as well as lesions of myelinic and unmyelinic fibers ascribable to Chagas'disease. In mice with experimentally induced Chagas' disease weobserved more intensive neuronal lesions of the cardiac ganglia in the acute phase of infection. Perhaps neuronal loss has a role in the pathogenesis of Chagas cardiomyopathy. However based on our own experience and on other data from the literature we conclude that the loss of neurones is not the main factor responsible for the manifestations exhibited by chronic chagasic patients. On the other hand the neuronal lesions may have played a role in the sudden death ofone group of patients with Chagas'disease but is difficult to explain the group of patients who did not die sudderly but instead progressed to cardiac failure.
Avaliação da estabilidade na contagem de ovos de Schistosoma mansoni pelo método de Kato-Katz em uma zona endêmica da esquistossomose
Authors: Costa Maria Fernanda F. de Lima e , Rocha R.S. , Katz Naftale
Published: June 2013

A estabilidade da contagem de ovos de Schistosoma mansoni pelo método de Kato-Katz foi avaliada em 144 pessoas residentes em uma área endêmica de Minas Gerais. Os resultados do primeiro exame foram comparados à média obtida em três exames de fezes realizados num período de 11 semanas. Os pacientes foram agrupados de acordo com a contagem de ovos obtida no primeiro exame de fezes: < 100, 100-499, 500-999 e ≥ 1000 ovos (classificação A); < 100, 100-499 e ≥ 500 ovos (classificação B); < 500, 500-999 e ≥ 1000 ovos (classificação C). A percentagem de pacientes que permaneceram no mesmo grupo no qual haviam sido enquadrados no primeiro exame foi estatisticamente semelhante nas classificações A, Be C (73-81%). O coeficiente de correlação de Pearson foi alto (r= 0,9038) e a média geométrica do número de ovos no primeiro exame (5 75,7 + 5,4) foi semelhante à obtida em três exames de fezes (556,6 + 4,4 ovos/g fezes).