Elucidating esterification reaction during deposition of cutin monomers from classical molecular dynamics simulations.

The structural behavior of some cutin monomers, when deposited on mica support, was extensively investigated by our research group. However, other events, such as esterification reaction (ER), are still a way to explore. In this paper, we explore possible ER that could occur when these monomers adsorb on support. Although classical molecular dynamics simulations are not able to capture reactive effects, here, we show that they become valuable strategies to analyze the initial structural configurations to predict the most favorable reaction routes. Thus, when depositing aleuritic acid (ALE), it is observed that the loss of capacity to form self-assembled (SA) systems favors different routes to occur ER. In pure ALE bilayers systems, an ER is given exclusively through the -COOH and primary -OH groups. In pure ALE monolayers systems, the ER does not happen when the system is self-assembled. However, for disorganized systems, it is able to occur by two possible routes: -COOH and primary -OH (route 1) and -COOH and secondary -OH (route 2). When palmitic acid (PAL) is added in small quantities, ALE SAMs can now form an ER. In this case, ER occurs mostly through the -COOH and secondary -OH groups. However, when the presence of PAL is dominant, ER can occur with either of both possibilities, that is, routes 1 and 2. Graphical abstract.

Understanding segregation processes in SAMs formed by mixtures of hydroxylated and non-hydroxylated fatty acids.

In this paper, we focus on the segregation processes emerging when preparing mixtures with different compositions of aleuritic (9,10,16 trihydroxyhexadecanoic) (ALE) and palmitic (hexadecanoic) (PAL) acids. The combination of atomic force microscopy (AFM) and molecular dynamics (MD) simulations enabled us to prove the role of the functional groups in the formation of self-assembled monolayers (SAMs) on muscovite mica surfaces. MD simulations indicate that segregation processes are favored in high ALE composition mixtures in agreement with the experimental evidence, whereas low ALE compositions promote the co-existence between segregated and dispersed systems. The secondary hydroxyl groups play a central role in the self-assembling mechanism because they control the formation of hydrogen bonding networks guarantying system stability.

[Microflora of nasal mucosa in patients with maxillar sinusitis].

Quantitative and qualitative composition of microflora of nasal mucosa as well as carriage of staphylococci was assessed in patients with chronic and acute forms of maxillary sinusitis. Changes in microflora of nasal mucosa and presence of pathogenic and persistence-associated characteristics of staphylococci in both forms of maxillary sinusitis were revealed. Increase of resistance staphylococci to antibiotics in patients with chronic form of maxillary sinusitis was shown.

Simultaneous detection of all four alkaline phosphatase isoenzymes in human germ cell tumors using reverse transcription-PCR.

We have developed a reverse transcription-PCR method that clearly distinguishes between the RNA transcripts of all four alkaline phosphatase (AP) genes. If compared to the methods used up to the present, the main advantages of the reverse transcription-PCR method presented are its specificity and high sensitivity. The germ cell AP and the placental AP, which are the two most closely related AP isoenzymes (98% homology), can clearly be distinguished without any interference by other AP isoenzymes. An enhanced expression of AP isoenzymes has been reported for various tumors. The examination of the pattern of AP isoenzyme expression in a specific tumor and the corresponding tissue of origin enables discrimination between eutopically and ectopically expressed isoenzymes and thus represents an important tool in the elucidation of AP isoenzymes as potential tumor markers. The pattern of AP expression in 15 germ cell tumors, 2 germinal epithelia adjacent to seminoma, 2 cell lines of germ cell tumor origin (Tera-1 and BeWo), and 5 normal testes was studied. In comparison to normal testes, in all seminomatous germ cell tumors eutopic expression of germ cell AP and ectopic expression of tissue-nonspecific AP were demonstrated. In both samples of pure embryonal carcinoma and in the embryonal carcinoma cell line, the transcription of all four mRNAs was shown. These results indicate that the expression of the isoenzymes depends on the degree of differentiation of a tumor and that a simultaneous up-regulation of all AP isoenzymes in all types of germ cell tumors does not exist.

Swiss Feline Cancer Registry 1965-2008: the Influence of Sex, Breed and Age on Tumour Types and Tumour Locations.

Cancer registries are valuable sources for epidemiological research investigating risk factors underlying different types of cancer incidence. The present study is based on the Swiss Feline Cancer Registry that comprises 51,322 feline patient records, compiled between 1965 and 2008. In these records, 18,375 tumours were reported. The study analyses the influence of sex, neutering status, breed, time and age on the development of the most common tumour types and on their locations, using a multiple logistic regression model. The largest differences between breeds were found in the development of fibrosarcomas and squamous cell carcinomas, as well as in the development of tumours in the skin/subcutis and mammary gland. Differences, although often small, in sex and neutering status were observed in most analyses. Tumours were more frequent in middle-aged and older cats. The sample size allowed detailed analyses of the influence of sex, neutering status, breed and age. Results of the study are mainly consistent with previous analyses; however, some results cannot be compared with the existing literature. Further investigations are necessary, since feline tumours have not been investigated in depth to date. More accurate comparisons would require the definition of international standards for animal cancer registries.

Swiss Feline Cancer Registry: A Retrospective Study of the Occurrence of Tumours in Cats in Switzerland from 1965 to 2008.

Cancer is one of the leading causes of death in companion animals. Information on the epidemiology of cancer is instrumental for veterinary practitioners in patient management; however, spontaneously arising tumours in companion animals also resemble those in man and can provide useful data in combating cancer. Veterinary cancer registries for cats are few in number and have often remained short-lived. This paper presents a retrospective study of tumours in cats in Switzerland from 1965 to 2008. Tumour diagnoses were coded according to topographical and morphological keys of the International Classification of Oncology for Humans (ICD-O-3). Correlations between breed, sex and age were then examined using a multiple logistic regression model. A total of 18,375 tumours were diagnosed in 51,322 cats. Of these, 14,759 (80.3%) tumours were malignant. Several breeds had significantly lower odds ratios for developing a tumour compared with European shorthair cats. The odds of a cat developing a tumour increased with age, up to the age of 16 years, and female cats had higher risk of developing a tumour compared with male cats. Skin (4,970; 27.05%) was the most frequent location for tumours, followed by connective tissue (3,498; 19.04%), unknown location (2,532; 13.78%) and female sexual organs (1,564; 8.51%). The most common tumour types were epithelial tumours (7,913; 43.06%), mesenchymal tumours (5,142; 27.98%) and lymphoid tumours (3,911; 21.28%).

Experimental closed head injury: analysis of neurological outcome, blood-brain barrier dysfunction, intracranial neutrophil infiltration, and neuronal cell death in mice deficient in genes for pro-inflammatory cytokines.

Cytokines are important mediators of intracranial inflammation following traumatic brain injury (TBI). In the present study, the neurological impairment and mortality, blood-brain barrier (BBB) function, intracranial polymorphonuclear leukocyte (PMN) accumulation, and posttraumatic neuronal cell death were monitored in mice lacking the genes for tumor necrosis factor (TNF)/lymphotoxin-alpha (LT-alpha) (TNF/LT-alpha-/-) and interleukin-6 (IL-6) and in wild-type (WT) littermates subjected to experimental closed head injury (total n = 107). The posttraumatic mortality was significantly increased in TNF/LT-alpha-/- mice (40%; P < 0.02) compared with WT animals (10%). The IL-6-/- mice also showed a higher mortality (17%) than their WT littermates (5.6%), but the difference was not statistically significant (P > 0.05). The neurological severity score was similar among all groups from 1 to 72 hours after trauma, whereas at 7 days, the TNF/LT-alpha-/- mice showed a tendency toward better neurological recovery than their WT littermates. Interestingly, neither the degree of BBB dysfunction nor the number of infiltrating PMNs in the injured hemisphere was different between WT and cytokine-deficient mice. Furthermore, the analysis of brain sections by in situ DNA nick end labeling (TUNEL histochemistry) at 24 hours and 7 days after head injury revealed a similar extent of posttraumatic intracranial cell death in all animals. These results show that the pathophysiological sequelae of TBI are not significantly altered in mice lacking the genes for the proinflammatory cytokines TNF, LT-alpha, and IL-6. Nevertheless, the increased posttraumatic mortality in TNF/LT-alpha-deficient mice suggests a protective effect of these cytokines by mechanisms that have not been elucidated yet.

Role of cerebral inflammation after traumatic brain injury: a revisited concept.

Neuroinflammation occuring after traumatic brain injury (TBI) is a complex phenomenon comprising distinct cellular and molecular events involving the injured as well as the healthy cerebral tissue. Although immunoactivation only represents a one of the many cascades initiated in the pathophysiology of TBI, the exact function of each mediator, activated cell types or pathophysiological mechanism, needs to be further elucidated. It is widely accepted that inflammatory events display dual and opposing roles promoting, on the one hand, the repair of the injured tissue and, on the other hand, causing additional brain damage mediated by the numerous neurotoxic substances released. Most of the data supporting these hypotheses derive from experimental work based on both animal models and cultured neuronal cells. More recently, evidence has been provided that a complete elimination of selected inflammatory mediators is rather detrimental as shown by the attenuation of neurological recovery. However, there are conflicting results reported on this issue which strongly depend on the experimental setting used. The history of immunoactivation in neurotrauma is the subject of this review article, giving particular emphasis to the comparison of clinical versus experimental studies performed over the last 10 years. These results also are evaluated with respect to other neuropathologies, which are years ahead as compared to the research in TBI. The possible reciprocal influence of peripheral and intrathecal activation of the immune system will also be discussed. To conclude, the future directions of research in the field of neurotrauma is considered.

Interleukin-6 and its soluble receptor in serum and cerebrospinal fluid after cerebral trauma.

Interleukin-6 (IL-6) and its soluble receptor (sIL-6-R) were measured in cerebrospinal fluid (CSF) and serum of 11 severely head injured patients for up to 3 weeks following trauma. IL-6 increased immediately after injury displaying much higher concentrations in CSF than in serum (n = 11). Differently, median levels of sIL-6-R remained in the normal ranges being 10 times higher in serum than in CSF. However, increased amounts over control levels were found in CSF (n = 7) and intrathecal release of sIL-6-R was also suggested (n = 7). Although no correlation with the extent of cerebral lesion or with clinical outcome was evident, elevation of sIL-6-R in CSF supports a pivotal role for IL-6/sIL-6-R complex in the injured brain.

Regulation of chemokines and chemokine receptors after experimental closed head injury.

The expression of the chemokines macrophage inflammatory protein (MIP)-2 and MIP-1alpha and of their receptors CXCR2 and CCR5 was assessed in wild type (WT) and TNF/lymphotoxin-alpha knockout (TNF/LT-alpha-/-) mice subjected to closed head injury (CHI). At 4 h after trauma intracerebral MIP-2 and MIP-1alpha levels were increased in both groups with MIP-2 concentrations being significantly higher in WT than in TNF/LT-alpha-/- animals (p < 0.05). Thereafter, MIP-2 production declined rapidly, whereas MIP-1alpha remained elevated for 7 days. Expression of CXCR2 was confined to astrocytes and increased dramatically within 24 h in both mouse types. Contrarily, CCR5 expression remained constitutively low and was mainly localized to microglia. These results show that after CHI, chemokines and their receptors are regulated differentially and with independent kinetics.

Abacavir/lamivudine/zidovudine as a combined formulation tablet: bioequivalence compared with each component administered concurrently and the effect of food on absorption.

A single-center, open-label, three-way crossover study was conducted in 24 healthy subjects to assess (1) the bioequivalence of a combined abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg (A/L/Z) combination tablet relative to the separate brand-name components administered simultaneously and (2) the effect of food on the bioavailability of the drugs from the combination tablet. The subjects were randomly assigned to receive each of the following three treatments, separated by a 2-day washout period: one A/L/Z combination tablet after an overnight fast, one abacavir 300 mg tablet + one lamivudine 150 mg tablet + one zidovudine 300 mg tablet sequentially after an overnight fast, or one A/L/Z combination tablet 5 minutes after completing a standardized high-fat breakfast (67 g fat, 58 g carbohydrate, and 33 g protein). Serial blood samples were collected up to 24 hours postdose for determination of abacavir, lamivudine, and zidovudine serum concentrations. Standard pharmacokinetic parameters were estimated. Treatments were considered bioequivalent if 90% confidence intervals (CI) for geometric least squares (GLS) mean ratios for abacavir, lamivudine, and zidovudine area under the serum concentration-time curve (AUC(infinity)) and maximum observed serum concentration (Cmax) fell entirely within 0.80 to 1.25 for log-transformed parameters. The combined A/L/Z tablet was bioequivalent in the extent (AUC) and rate of absorption (Cmax and time of Cmax [tmax]) to the individual brand-name drug components administered concurrently under fasted conditions. GLS ratios and 90% CI for AUC(infinity) and Cmax were 0.99 (0.96, 1.03) and 1.00 (0.90, 1.11), respectively, for abacavir; 0.95 (0.91, 0.99) and 0.90 (0.84, 0.99), respectively, for lamivudine; and 0.95 (0.89, 1.02) and 0.96 (0.80, 1.15), respectively, for zidovudine. The extent of absorption of abacavir, lamivudine, and zidovudine from the combination tablet was not altered by administration with meals, indicating that this formulation may be administered with or without food. However, food slowed the rate of absorption, delayed the tmax, and reduced the Cmax of abacavir, lamivudine, and zidovudine. These changes, which were consistent with those observed with the individual reference formulations when administered with food, were not considered clinically important. All formulations were well tolerated underfasted and fed conditions.

Specific determination of germ cell alkaline phosphatase for early diagnosis and monitoring of seminoma: performance and limitations of different analytical techniques.

Two-dimensional electrophoresis, ion-exchange chromatography and immunoassay were evaluated in order to improve the diagnostic specificity of the germ cell specific isoenzyme of alkaline phosphatase (GCAP) for the detection of seminoma. Assessment of GCAP is hampered by its structural heterogeneity and low serum concentration. The structural heterogeneity of GCAP from seminoma tissue could be clearly visualized by two-dimensional electrophoresis. We inferred that it depended on allelic amino acid substitutions, varying sialylation and differential cleavage of the membrane anchor. The allelic variability of GCAP affects the accuracy of immunological measurements. However, immunoassay was found to be the only technique sensitive enough to assess GCAP in serum. The elevated GCAP levels in 15% of healthy blood donors were shown to be correlated with smoking. Further studies clarifying how to interpret the values measured in smokers are prerequisite for the introduction of GCAP as a serum marker for seminoma. In the future, GCAP might be utilized for the detection of carcinoma in situ (CIS) cells in ejaculate. Assessment of the enhanced expression of cellular GCAP by CIS cells exfoliated into ejaculate could be a means for noninvasive, early diagnosis that presumably will not be hampered by the patient's smoking habits.

Resource partitioning of sonar frequency bands in rhinolophoid bats.

In the Constant Frequency portions of the orientation calls of various Rhinolophus and Hipposideros species, the frequency with the strongest amplitude was studied comparatively. (1) In the five European species of the genus Rhinolophus call frequencies are either species-specific (R. ferrumequinum, R. blasii and R. euryale) or they overlap (R. hipposideros and R. mehelyi). The call frequency distributions are approximately 5-9 kHz wide, thus their ranges spead less than ±5% from the mean (Fig. 1). Frequency distributions are considerably narrower within smaller geographic areas. (2) As in other bat groups, call frequencies of the Rhinolophoidea are negatively correlated with body size (Fig. 3). Regression lines for the genera Rhinolophus and Rhinolophus, species from dryer climates have on the average higher call frequencies than species from tropical rain forests. (4) The Krau Game Reserve, a still largely intact rain forest area in Malaysia, harbours at least 12 syntopic Rhinolophus and Hipposiderso species. Their call frequencies lie between 40 and 200 kHz (Fig. 2). Distribution over the available frequency range is significantly more even than could be expected from chance alone. Two different null hypotheses to test for random character distribution were derived from frequency-size-relations and by sampling species assemblages from a species pool (Monte Carlo method); both were rejected. In particular, call frequencies lying close together are avoided (Figs. 4, 5). Conversely, the distribution of size ratios complied with a corresponding null hypothesis. This even distribution may be a consequence of resource partitioning with respect to prey type. Alternatively, the importance of these calls as social signals (e.g. recognition of conspecifics) might have necessitated a communication channel partitioning.

[Possible triggers of decompensated chronic complex tinnitus with a therapeutic approach as relating to treatment of epilepsy]. / Möglicher Auslöser des dekompensierten chronisch komlexen Tinnitus mit einem Therapieansatz analog zur Behandlung der Epilepsie.

Coxsackieviruses are responsible for numerable diseases in man. This is also the reason for the high prevalence of endemic infection rates in the population. Our analysis (working hypothesis) will focus on the participation of Coxsackieviruses in chronic decompensated, complex tinnitus. Examination of the Coxsackievirus antibody titers might reveal the extent to which a Coxsackieviruses-triggered disease of the central nervous system participates in the direct sequelae of tinnitus disorders. A spread of Coxsackieviruses to the auditory pathway might lead to an overstimulation of the auditory pathway, comparable to an epileptic lesion. Based on this assumption, treatment with an antiepileptic would make sense. The reasoning behind this working hypothesis is to find a potentially new diagnostic and therapeutic roadmap as a further guide for specialized clinics. The authors are well aware that previous results bear little relevance as they have been based on small case numbers.

[Neurologic complications in hypereosinophilia syndrome--a case report]. / Neurologische Komplikationen beim hypereosinophilen Syndrom--eine Falldarstellung.

The idiopathic hypereosinophilic syndrome (HES) is a rare disease characterised by prolonged eosinophilia of undetectable cause and by the presence of varying internal symptoms and frequent neurological signs. We report on a 43-year old man with HES who developed cerebral infarction and organic psychosyndrome. Chemotherapy resulted in lower eosinophil counts and marked improvement of central nervous system dysfunction. We comment on possible pathophysiologic mechanisms of central nervous system involvement in HES.

Mycological culture media and its quality control.

The need for control of the quality of media used in the isolation and identification of fungi is an important aspect of the overall quality control of laboratory culture media; however, guidelines for such controls have not been available. In this paper, primary isolation media with and without appropriate drugs are suggested for use on a variety of specimens. Positive and negative quality control organisms that indicate clear-cut postiive and negative results on the fungal media to be tested are listed. Several alternative procedures for maintenance of fungi are discussed.