Effects of p.o. administered xylitol in cats.

Xylitol is commonly used as sugar substitute in households. While it has numerous beneficial effects on human health, it is highly toxic to dogs. The goal of this study was to examine whether xylitol has similar deleterious effects, such as hypoglycaemia and acute hepatic failure, on cats. Our research included six healthy middle-aged cats. Xylitol was dissolved in deionized water and administered p.o. at three doses (100, 500 and 1,000 mg/kg body weight). These dosages have been considered toxic and can cause liver failure or even death in dogs. After every xylitol administration, the basic health status and the blood glucose of cats were observed regularly. Additionally, prior to and 6, 24 and 72 hr after xylitol administration, blood samples were taken to check complete blood count, clinical biochemical parameters and enzymes such as ALT, ALKP, GGT, GLDH, bile acids, BUN, creatinine, phosphate, total protein, albumin, sodium and potassium. There were no significant changes (p > .05) in any of the haematological or biochemical parameters. Blood glucose concentrations did not show any significant alterations, except at 1,000 mg/kg dose, where a mild but significant increase was observed, but it was in physiological range. Based on our results, xylitol did not induce toxic effects on cats.

Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin.

Quinolones are potent antimicrobial agents with a basic chemical structure of bicyclic ring. Fluorine atom at position C-6 and various substitutions on the basic quinolone structure yielded fluoroquinolones, namely norfloxacin, ciprofloxacin, levofloxacin, moxifloxacin and numerous other agents. The target molecules of quinolones and fluoroquinolones are bacterial gyrase and topoisomerase IV enzymes. Broad-spectrum and excellent tissue penetration make fluoroquinolones potent agents but their toxic side effects and increasing number of resistant pathogens set limits on their use. This review focuses on recent advances concerning quinolones and fluoroquinolones, we will be summarising chemical structure, mode of action, pharmacokinetic properties and toxicity. We will be describing fluoroquinolones introduced in clinical trials, namely avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and non-fluorinated nemonoxacin. These agents have been proved to have enhanced antibacterial effect even against ciprofloxacin resistant pathogens, and found to be well tolerated in both oral and parenteral administrations. These features are going to make them potential antimicrobial agents in the future.

Fitness cost associated with resistance to fluoroquinolones is diverse across clones of Klebsiella pneumoniae and may select for CTX-M-15 type extended-spectrum ß-lactamase.

Lowered fitness cost associated with resistance to fluoroquinolones was recently demonstrated to influence the clonal dynamics of methicillin-resistant Staphylococcus aureus (MRSA) in the health care setting. We investigated whether or not a similar mechanism impacts Klebsiella pneumoniae. The fitness of K. pneumoniae isolates from major international hospital clones (ST11, ST15, ST147) already showing high-level resistance to fluoroquinolones and of strains from three minor clones (ST25, ST274, ST1028) in which fluoroquinolone resistance was induced in vitro was tested in a propagation assay. Strains from major clones showed significantly less fitness cost than three of four fluoroquinolone-resistant derivatives of minor clone isolates. In addition, plasmids with CTX-M-15 type extended-spectrum ß-lactamase (ESBL) genes were all retained in both major and minor clone isolates, irrespective of the strains' level of fluoroquinolone resistance, while each plasmid harboring SHV-type ESBLs had been lost during the induction of resistance. Major clone K. pneumoniae strains harbored more amino acid substitutions in the quinolone resistance determining regions (QRDRs) of the gyrA and parC genes than minor clone isolates. The presence of an active efflux system could be demonstrated in all fluoroquinolone-resistant derivatives of originally SHV-producing minor clone isolates but not in any CTX-M-15-producing strain. Further investigations are needed to expand and confirm our findings on a larger sample. In addition, a long-term observation of our ciprofloxacin-resistant minor clone isolates is required in order to elucidate whether or not they are capable of restoring their fitness while concomitantly retaining high minimum inhibitory concentration (MIC) values.

Recurrent outbreaks of Serratia marcescens among neonates and infants at a pediatric department: an outbreak analysis.

PURPOSE: Serratia marcescens is a known cause of bloodstream infections (BSIs) and outbreaks in neonates receiving intensive care. Our aim was to analyze clinical and epidemiological characteristics of two outbreaks detected in our unit to prevent and control further epidemic infections. METHODS: Two episodes of BSI outbreaks in neonates have been investigated in a 20-month period at a pediatric department of a medical university in Hungary. We collected all S. marcescens strains that were isolated in the study period, and two strains that were isolated before the outbreaks. Strains were analyzed by pulsed-field gel electrophoresis (PFGE). Clinical data were collected for the BSIs during and between the outbreaks (n = 14). RESULTS: Out of the 28 S. marcescens isolates investigated by PFGE, 16 were blood isolates. All isolates represented four PFGE types. Pathogenic strains that caused epidemic BSIs were related to a single PFGE type (SM009). Strains with the same pulsotype could be detected before, between, and after the outbreak periods from surveillance cultures of neonates, and a water tap in the infant care unit despite intensive infection control measures. Case fatality rate of BSIs was 29%. Rate of complications in central nervous system was high: 3/14 neonates developed meningitis. CONCLUSIONS: Rapid spread and high mortality rate of S. marcescens infections necessitate a high suspicion when isolating this species in neonatal intensive care. Early identification of outbreaks is essential, that can be facilitated by determination of clonal relatedness using molecular methods, and with regular surveillance cultures of patients and environment.

In silico analysis of pathways affected by differentially expressed microRNA in adrenocortical tumors.

BACKGROUND: MicroRNA are involved in the pathogenesis of several tumors, and several studies have been performed on the microRNA profile of adrenocortical tumors to date. The pathways affected by these microRNA, however, have not been analyzed yet by a systematic approach. AIM: To perform an in silico bioinformatics analysis of microRNA commonly altered in at least two studies and to decipher the pathways affected by microRNA in adrenocortical tumors. METHODS: Datasets on microRNA and mRNA expression have been retrieved from 5 and 3 studies, respectively. MicroRNA mRNA targets have been identified by our tissue specific target prediction pipeline, and mRNA have been subjected to Ingenuity Pathway Analysis. RESULTS: Thirty- nine microRNA were identified as commonly altered in two studies. Altogether 49,817 mRNA targets have been found for these microRNA. One-hundred and seventy-eight significant pathways associating with these have been identified and were found in all studies. We have selected 12 pathways involving retinoic acid signaling (lipopolysaccharide/ interleukin-1 mediated inhibition of retinoic X receptor (RXR) function, peroxisome proliferator-activated receptor (PPAR)α/RXRα activation, retinoic A receptor activation and PPAR signaling pathways) and cell cycle alterations (aryl hydrocarbon receptor signaling, growth arrest and DNA damage-inducible 45 signaling, integrin signaling, G2/M DNA damage checkpoint regulation, cyclins and cell cycle regulation and cell cycle control of chromosomal replication pathways) as these have been also established in our previous study on the functional genomics meta-analysis of adrenocortical tumors. Several microRNA have been identified that could affect these pathways. CONCLUSIONS: MicroRNA might affect several pathogenic pathways in adrenocortical tumors. Validation studies are required to confirm the biological relevance of these findings.

Significance of methicillin-teicoplanin resistant Staphylococcus haemolyticus in bloodstream infections in patients of the Semmelweis University hospitals in Hungary.

The purpose of this study was to quantify the impact of Staphylococcus haemolyticus in the epidemiology of the blood stream infection (BSI) and to characterize the rates and quantitative levels of resistance to antistaphylococcal drugs. During an eight-year period, 2967 BSIs of the patients hospitalized in different clinical departments of the Semmelweis University, Budapest, Hungary were analyzed. One hundred eighty-four were caused by S. haemolyticus, amounting to 6% of all infections. The antibacterial resistance of S. haemolyticus isolates was investigated by the broth microdilution method, vancomycin agar screen, population analysis profile and PCR for mecA, vanA and vanB genes detection. Epidemiological investigation was processed by determining phenotypic antibiotic resistance patterns and PFGE profiles. Extremely high MIC levels of resistance were obtained to oxacillin, erythromycin, clindamycin, gentamicin and ciprofloxacin. The incidence of teicoplanin reduced susceptibility revealed 32% without possessing either the vanA or vanB gene by the strains. PFGE revealed 56 well-defined genotypes indicating no clonal relationship of the strains. The propensity of S. haemolyticus to acquire resistance and its pathogenic potential in immunocompromised patients, especially among preterm neonates, emphasise the importance of species level identification of coagulase-negative staphylococci and routinely determine the MIC of proper antibacterial agents for these isolates.

Carpal canal lipoma causing lameness in a dog.

Carpal canal syndrome, or carpal tunnel syndrome, is the most common entrapment neuropathy in humans and is caused by compression of the median nerve as it courses through the carpal canal. A similar condition has been reported in horses, however there have not been any reported cases of a dog showing lameness secondary to compression within the carpal canal. This report describes the case of a dog exhibiting lameness secondary to a lipoma within the carpal canal. Lameness improved after surgical removal of the mass. This case highlights the need to consider compression of the tendons and nerves in the carpal canal as a cause of forelimb lameness in dogs when pain is localised to the carpus.

Zabofloxacin for chronic bronchitis.

Treatment of lower respiratory tract infection poses as an ongoing challenge among respiratory tract diseases. Bacterial infections are causes of acute exacerbations in chronic bronchitis and indications for antibacterial therapy. Several antibiotics were applied to treat bacterial infections in chronic bronchitis, among them fluoroquinolones are considered potent, broad-spectrum agents with excellent tissue penetration. This monograph focuses on zabofloxacin, a novel fluoroquinolone agent recently approved and launched in South Korea, and summarizes the drug's antibacterial efficacy, pharmacokinetic properties and toxicity. Recent advances concerning fluoroquinolones in chronic bronchitis will be discussed, along with a comparison between zabofloxacin and moxifloxacin. Zabofloxacin has proved to be noninferior to moxifloxacin against major community-acquired Gram-positive and Gram-negative respiratory tract pathogens and found to be well tolerated in both oral and parenteral administrations. These features can make it a potential antimicrobial agent in therapy of chronic bronchitis and other lower respiratory tract infections.

Neural mechanisms for lexical processing in dogs.

During speech processing, human listeners can separately analyze lexical and intonational cues to arrive at a unified representation of communicative content. The evolution of this capacity can be best investigated by comparative studies. Using functional magnetic resonance imaging, we explored whether and how dog brains segregate and integrate lexical and intonational information. We found a left-hemisphere bias for processing meaningful words, independently of intonation; a right auditory brain region for distinguishing intonationally marked and unmarked words; and increased activity in primary reward regions only when both lexical and intonational information were consistent with praise. Neural mechanisms to separately analyze and integrate word meaning and intonation in dogs suggest that this capacity can evolve in the absence of language.

Knowledge of Emergency Contraceptive Pills among Hungarian Women Presenting for Induced Abortion or Seeking Emergency Contraception.

Aim: To compare the differences in contraceptive characteristics and the knowledge of emergency contraception (ECP) among women who used ECP after unprotected intercourse and those who sought an abortion. Methods: A questionnaire survey was conducted in a Hungarian university hospital among women for whom ECP was prescribed after unprotected intercourse (n = 940) as well as women who presented for the termination of pregnancy (n = 1592) between January 1, 2005 and November 20, 2006. Their knowledge of ECP and their experience with and attitudes toward ECP use were targeted. Results: The availability of ECP was well known (87.9 %), but it was still greatly underutilized: applied by only 13 of the 1592 women who resorted to abortion. Primarily, the ECP group consisted of those who experienced a condom failure significantly more often (odds ratio [OR] = 4.1), followed by those cases where ECP applications was a consequence of not using any kind of contraception (OR = 3.8). Fewer than one third (32 %) of the abortion seekers had previously used ECP, and only one fifth knew how to obtain it. Appropriate awareness of ECP was influenced by information obtained from health-care providers (adjusted odds ratio [AOR] = 3.93) or school education (AOR = 1.82). Conclusions: More thorough education is needed to provide a deeper knowledge of ECP use during contraceptive counseling for women seeking abortion, including those contraceptive mishaps where unintended pregnancy can be prevented by ECP.

Primary peritoneal adenocarcinoma as content of an incarcerated umbilical hernia: A case-report and review of the literature.

INTRODUCTION: Umbilical hernia is a common finding in many cases, posing potentially life-threatening complications, such as incarceration or strangulation. The presence of malignancy in hernia sacs is, however, rather rare. PRESENTATION OF CASE: Here we report on a case of primary peritoneal adenocarcinoma found through histological examination of omental tissue, resected due to an incarcerated umbilical hernia of an 84-years-old woman. There was no macroscopic sign of malignancy during operation; only after routine examination of histological sections the diagnosis was found. DISCUSSION: To our knowledge this is the first report of primary peritoneal cancer as content of an umbilical hernia. This is a rare neoplasm and histologically identical to epithelial ovarian carcinoma. For this reason, the diagnosis is usually based on the histological finding and exclusion of a primary ovarian tumor. Primary peritoneal cancer has a poor outcome in general. Early diagnosis is, therefore, essential for effective treatment. CONCLUSION: Histological analysis of resected hernia sac or content should be performed routinely to discover malignant diseases in the background of a hernia.

Comprehensive analysis of TEM methods for LiFePO4/FePO4 phase mapping: spectroscopic techniques (EFTEM, STEM-EELS) and STEM diffraction techniques (ACOM-TEM).

Transmission electron microscopy (TEM) has been used intensively in investigating battery materials, e.g. to obtain phase maps of partially (dis)charged (lithium) iron phosphate (LFP/FP), which is one of the most promising cathode material for next generation lithium ion (Li-ion) batteries. Due to the weak interaction between Li atoms and fast electrons, mapping of the Li distribution is not straightforward. In this work, we revisited the issue of TEM measurements of Li distribution maps for LFP/FP. Different TEM techniques, including spectroscopic techniques (energy filtered (EF)TEM in the energy range from low-loss to core-loss) and a STEM diffraction technique (automated crystal orientation mapping (ACOM)), were applied to map the lithiation of the same location in the same sample. This enabled a direct comparison of the results. The maps obtained by all methods showed excellent agreement with each other. Because of the strong difference in the imaging mechanisms, it proves the reliability of both the spectroscopic and STEM diffraction phase mapping. A comprehensive comparison of all methods is given in terms of information content, dose level, acquisition time and signal quality. The latter three are crucial for the design of in-situ experiments with beam sensitive Li-ion battery materials. Furthermore, we demonstrated the power of STEM diffraction (ACOM-STEM) providing additional crystallographic information, which can be analyzed to gain a deeper understanding of the LFP/FP interface properties such as statistical information on phase boundary orientation and misorientation between domains.

Tumor markers (pregnancy protein 1, placental-specific tissue protein 10, placental-specific tissue protein 12, alpha1-fetoprotein) in patients with bronchial carcinoma.

The concentrations of pregnancy protein 1 (SP1), placental-specific tissue protein 10 (PP10), placental-specific tissue protein 12 (PP12) and alpha1-Fetoprotein (AFP) were analyzed in serum samples of 83 patients with bronchial carcinoma at stages II-IV Protein levels were determined by means of single radial immunodiffusion, rocket immuno-electrophoresis, radioimmunoassay and enzyme- immunoassay. PP12 and AFP serum concentrations were significantly increased in the cancer group compared with the control group. PP12 (control group: x=54.08 microg/l; s=61. 70; tumor group: x = 122.52 microg/l; s = 131.16); AFP (control group: x=3.05 microg/l; s=3. 76; tumor group: x = 8.29 microg/l; s = 17.75). SPI was found in only 22 cases of the tumor group. PP10 (control group: x = 2.25 microg/l; s = 0.866; tumor group: x = 2.503 microg/l; s=1.508). Given that at least two of the tested parameters were determined to be in the pathological range, the sensitivity amounted to 0.64 and the specificity to 0.92.

Polymers and formulation strategies of nanofibrous systems for drug delivery application and tissue engineering.

During the last decade, the formulation of nanofibrous materials loaded with different drugs for biomedical applications has evoked considerable interest. The large specific surface area, the special micro- and macrostructure of fiber mats, the possibility for gradual release and site-specific local delivery of the active compounds lead to cytotoxicity decrease and enhancement of the therapeutic effect of drugs and implants. The present review details the different spinning techniques applied for the design of micro- and nanofibrous drug delivery systems. It furthermore deals with the use of various polymers that are capable for the formation of fiber scaffolds of various biomedical applications.

Anti-psychotic drugs reverse multidrug resistance of tumor cell lines and human AML cells ex-vivo.

Anti-psychotic drugs are used in cancer patients undergoing chemotherapy frequently and the concomitantly used drugs may alter the pharmacokinetics of each other. One reason for the alteration of pharmacokinetics may be the modulation of the function of P-glycoprotein, whose efflux pump occurs in resistant cancer cells, in human intestine and in the blood-brain barrier. For this reason we tested the effect of several anti-psychotic drugs on the multidrug-resistant pump, P-glycoprotein. We found that in the MDR gene transfected L121C MDR, L5178 MDR and in the KB-V-1 cells selected for resistance some antipsychotic drugs block the function of P-glycoprotein. Blood cells of two treatment-resistant leukemic patients also showed increased uptake of daunorubicin if treated ex vivo with the anti-psychotic drugs. Our results suggest that pharmacokinetic studies should be performed prior to concomitant clinical use of such drugs which block P-glycoprotein function.

Catecholamines released from local adrenergic axon terminals are possibly involved in fine tuning of steroid secretion from zona glomerulosa cells: functional and morphological evidence.

The effect of supramaximal electric field stimulation on [3H]noradrenaline (NA) release and hormone production by rat adrenal capsule-glomerulosa preparations was studied using a microvolume perfusion system. A substantial proportion (about 20%) of nerve endings (varicosities) were observed close to zona glomerulosa cells, and about half of them appeared to be catecholaminergic, as judged by the chromaffin reaction of the synaptic vesicles studied at electron microscopic level. In tissue, preloaded with [3H]NA, the release of NA in response to electrical stimulation was frequency-dependent. Reserpinization, calcium removal or inhibition of Na+ influx by tetrodotoxin completely blocked NA release by field stimulation, indicating that the release resulted from axonal activity and is of vesicular origin. Neither the alpha 2-adrenoceptor agonist xylazine nor the muscarine-receptor agonist oxotremorine affected the stimulation-evoked release of [3H]NA, suggesting that, in contrast with other neurones present in the central nervous system or in the peripheral autonomic nervous system but like those in the median eminence, these axon terminals contained few presynaptic modulatory receptors. The NA (10.20 +/- 1.79 (S.E.M.) micrograms/g, n = 9), adrenaline (24.38 +/- 5.50 micrograms/g, n = 9) and dopamine (0.35 +/- 0.09 micrograms/g, n = 6) contents of the preparations were high, as determined by high-performance liquid chromatography. Our observations that the release and content of NA is high, and that a substantial proportion of catecholaminergic axon terminals lie in close proximity to zona glomerulosa cells (median value of the distance 300 nm) or to smooth muscle cells of the vessels, suggest that NA released from local adrenergic neurones without being presynaptically modulated may play an important role in fine-tuning both steroid production and/or blood flow through the gland, itself a powerful modulator of the adrenocortical response. This local modulating effect of NA may be especially significant when sympathetic activity is enhanced.

Dopamine is taken up from the circulation by, and released from, local noradrenergic varicose axon terminals in zona glomerulosa of the rat: a neurochemical and immunocytochemical study.

The effect of supramaximal electric field stimulation on [3H]dopamine (DA) release by rat adrenal capsule-glomerulosa preparations was studied using a micro-volume perfusion system. When the tissues were preloaded with [3H]DA, a considerable amount of [3H]DA and [3H]noradrenaline (NA) were released in response to field stimuli. Reserpinization, calcium removal or tetrodotoxin blocking of Na+ influx all completely inhibited the stimulation-evoked release of DA/NA, indicating that the radioactivity released is of neuronal and vesicular origin. In the adrenal cortex, a substantial proportion of tyrosine hydroxylase and dopamine-beta-hydroxylase immunoreactive nerve fibres and varicosities were observed around the zona glomerulosa. DA-containing nerves were not seen in the adrenal cortex; however, the same immunocytochemical procedures clearly demonstrated dopaminergic nerve cells and fibres in the substantia nigra and the striatum respectively, and cells of the adrenal medulla. Like the NA release from noradrenergic varicosities in the zona glomerulosa, the DA release from noradrenergic endings is not subject to negative feedback modulation through DA2 receptors since apomorphine, a DA2-receptor agonist, and sulpiride, a selective DA2-receptor antagonist, failed to affect the release. After in-vivo i.v. administration of [3H]DA, the glomerulosa content of DA and NA and the in-vitro release of [3H]DA and [3H]NA of zona glomerulosa both increased, indicating that the local varicose axon terminals were able to accumulate DA from the circulation, convert it into NA and release it in response to neural activity. This local arrangement of noradrenergic axon terminals, able to take up DA from the circulation and release it or convert it into NA, provides the possibility of a fine tuning of local circulation and aldosterone synthesis in the zona glomerulosa.

Immunohistochemical localization of pregnancy-related placental protein 4 in human placenta, umbilical cord and adult human female genital tissues.

Placental protein 4 (PP4) is a soluble placental tissue protein which was isolated from human placenta. The aim of the present study was to demonstrate the localization of cells containing PP4 in human placenta and in various female genital tissues under normal conditions. PP4 immunoreactive structures were demonstrated by using the peroxidase-antiperoxidase immunohistochemical technique. The samples were obtained from normal human placenta, umbilical cord, uterine cervix, endometrium, ovary and vulva. The most differentiated trophoblastic cells, the syncytiotrophoblasts, as well as the intermediate trophoblast cells contained PP4. PP4 immunoreactivity was present in umbilical cord as well. Occasionally PP4 was detected in normal ovarian, endometrial or vulvar tissue samples. Cervix and myometrium were free of PP4 immunoreactive material. PP4 staining was cytoplasmic. Our findings indicate that PP4 cannot be considered specific for the placenta since it is present in some human adult tissues as well.

Correlation of lipid droplet content and steroidogenic capacity in zona glomerulosa and fasciculata cells from lipoprotein-deficient rats.

Lipoprotein deficiency was maintained for 48 h by applying 4-aminopyrazolo(3,4-d)pyrimidine in male albino rats and the effect on the structure and function of isolated adrenocortical cells was investigated. Neither the morphology nor the steroidogenic response of zona glomerulosa cells changed; however, in the zona fasciculata cells a marked reduction in the quantity of lipid droplets was associated with a decreased steroidogenic response to ACTH. The results indicate that despite lipoprotein deficiency, zona glomerulosa cells contain a reserve of intracellular cholesterol, thus retaining their responsiveness to stimulation. The fact that the lipoprotein deficiency does not affect lipid droplets located in the glomerulosa cells and in the fasciculata cells in a similar manner is probably due to the differences in their physical state and chemical composition.

Morphological evidence of lysosomal uptake of high-density lipoproteins by rat adrenocortical cells in vitro.

The high-density lipoprotein (HDL) pathway in rat adrenocortical cells was studied at the electron microscopic level in vitro via colloidal gold labelling. Steroid hormone assays were performed to confirm that the cells remained intact, viable, responsive to ACTH under the applied conditions, and to reveal the steroidogenic effect of HDL. The gold-labelled HDL particles (HDL-Au) were observed on the surface of the parenchymal cells, often attached to the membranes of the microvilli, but rarely in coated pits and coated vesicles. HDL-Au was accumulated by non-coated vesicles, multivesicular bodies and lysosomes. The lysosomes were identified by means of a non-specific esterase reaction. It is concluded that HDL particles are internalized by both zona glomerulosa and zona fasciculata cells. HDL is required for the enhanced functional activity of these cells in long-term incubation, and the lysosomes are involved in the process.