Schindleria elongata, a new species of paedomorphic gobioid from the Red Sea (Teleostei: Schindleriidae).

A new species of paedomorphic gobioid, Schindleria elongata, from the Red Sea, is described on the basis of five specimens. The new species is characterized by its lack of body pigmentation; the body depth at pectoral-fin origin 4-5% of standard length (LS ) and at anal-fin origin 5-7% LS ; the predorsal length 66-70% LS ; pre-anal length 66-71% LS ; dorsal-fin rays 13 or 14; anal-fin rays 10 or 11; first dorsal-fin ray at myomere 20 or 21; first anal-fin ray below second to fourth dorsal-fin rays; myomeres 19 or 20 + 13 or 14 = 33 or 34 total; premaxillae and dentaries with small teeth; gas bladder located posteriorly at 56-60% LS ; males with a rod-like, flexible urogenital papilla lacking lobes, projections or accessory papillae, with distal half tapering to a broad, angular point and usually posteriorly directed. A key to the species of Schindleriidae is presented.

[Massive bleeding of the urogenital tract]. / Massive Urogenitalblutung.

Massive bleeding of the urogenital tract is, in the same way as acute bleeding from all other organs, a medical emergency and necessitates precise diagnostics and treatment. In this article the topic is addressed in four main categories: first the inflammatory causes are discussed, followed by surgical, traumatic and neoplastic causes of massive bleeding. Subsequently, the rare but clinically relevant causes of acute and massive bleeding are described.

Callionymus omanensis, a new species of dragonet from Oman, north-western Indian Ocean (Teleostei: Callionymidae).

A new species of deep-living dragonet Callionymus omanensis from Oman is described on the basis of a single male specimen collected in a trawl from 500 m depth off the coast of Oman. The new species is characterized within the subgenus Bathycallionymus by having a small branchial opening; head short (3·9 in proportion to standard length); eye large (2·4 in proportion to head length); preopercular spine with a long, upcurved main tip, with a small antrorse barb and a larger antrorse spine, and with a strong antrorse spine laterally at the preopercular-spine base, ventral margin smooth; first dorsal fin slightly higher than second dorsal fin (male); second dorsal fin distally straight; 17 pectoral fin rays; distal end of caudal fin slightly pointed, with two median unbranched rays bearing short filaments; first dorsal fin with basal black spot reaching from first to fourth membranes, third membrane with an ocellated distal black blotch; second dorsal fin with vertical dark grey bars; distal three-fourths of anal fin black; upper half of caudal fin with oblique dark grey bars; pelvic fin dark grey, second ray basally with a black blotch. The new species is compared with similar species. Revised keys to callionymid species of the western Indian Ocean and the Red Sea, as well as species of the subgenus Bathycallionymus, are presented.

[Cohort study of cancer incidence in patients with type 2 diabetes: record linkage of encrypted data from an external cohort with data from the epidemiological Cancer Registry of North Rhine-Westphalia]. / Kohortenstudie zur Krebsinzidenz bei Patienten mit Diabetes mellitus Typ 2 : Record Linkage von kryptografierten Daten einer externen Kohorte mit Daten des Epidemiologischen Krebsregisters Nordrhein-Westfalen.

INTRODUCTION: German epidemiologic cancer registries may store only encrypted personal identifiers. Thus, record linkage with secondary databases needs to be performed via procedures that are based on encrypted identifiers. In this paper, we describe the linkage of patient data from a statutory health insurance company (AOK NordWest) and from the Disease Management Program for diabetes mellitus type 2 with the database of the cancer registry. We report the cancer incidence in patients with type 2 diabetes (T2D). METHODS: Personal identifying variables of the patient cohort were encrypted before being sent electronically to the cancer registry and submitted to a probabilistic record linkage with registry data. The study included T2D patients who were residents of the Münster, Detmold, or Arnsberg districts and who were aged 40-79 years. Only primary cancers occurring between the date of enrolment and the censoring date (31 December 2010) were included. The standardized incidence ratio (SIR) was calculated relative to the number of incident cases expected on the basis of the averaged incidence rates in the general population. RESULTS: The record linkage took about 3 weeks of processing time. A total of 67,447 T2D (49.2 % men) cases were included for analyses. Incident cancer was diagnosed in 2,086 men and 1,578 women. Cohort members showed an elevated risk for cancer of the liver (SIR =1.86; 95% CI =1.47-2.31), pancreas (SIR = 1.62; 95 % CI =1.36-1.91), lung (SIR = 1.21; 95% CI 1.11-1.32), and uterus (SIR = 1.34; 95 % CI 1.08-1.65), and they were less likely to be diagnosed with prostate cancer (SIR =0.72; 95% CI = 0.65-0.79). DISCUSSION: The findings of this study suggest that record linkage of secondary databases with cancer registry data for research purposes can be effectively carried out in compliance with strict data-protection regulations.

Age-dependent microRNA control of synaptic plasticity in 22q11 deletion syndrome and schizophrenia.

The 22q11 deletion syndrome (22q11DS) is characterized by multiple physical and psychiatric abnormalities and is caused by the hemizygous deletion of a 1.5-3 Mb region of chromosome 22. It constitutes one of the strongest known genetic risks for schizophrenia; schizophrenia arises in as many as 30% of patients with 22q11DS during adolescence or early adulthood. A mouse model of 22q11DS displays an age-dependent increase in hippocampal long-term potentiation (LTP), a form of synaptic plasticity underlying learning and memory. The sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA2), which is responsible for loading Ca(2+) into the endoplasmic reticulum (ER), is elevated in this mouse model. The resulting increase in ER Ca(2+) load leads to enhanced neurotransmitter release and increased LTP. However, the mechanism by which the 22q11 microdeletion leads to SERCA2 overexpression and LTP increase has not been determined. Screening of multiple mutant mouse lines revealed that haploinsufficiency of Dgcr8, a microRNA (miRNA) biogenesis gene in the 22q11DS disease-critical region, causes age-dependent, synaptic SERCA2 overexpression and increased LTP. We found that miR-25 and miR-185, regulators of SERCA2, are depleted in mouse models of 22q11DS. Restoration of these miRNAs to presynaptic neurons rescues LTP in Dgcr8(+/-) mice. Finally, we show that SERCA2 is elevated in the brains of patients with schizophrenia, providing a link between mouse model findings and the human disease. We conclude that miRNA-dependent SERCA2 dysregulation is a pathogenic event in 22q11DS and schizophrenia.

The effect of social experience on serotonergic modulation of the escape circuit of crayfish.

The neuromodulator serotonin has widespread effects in the nervous systems of many animals, often influencing aggression and dominance status. In crayfish, the effect of serotonin on the neural circuit for tailflip escape behavior was found to depend on the animal's social experience. Serotonin reversibly enhanced the response to sensory stimuli of the lateral giant (LG) tailflip command neuron in socially dominant crayfish, reversibly inhibited it in subordinate animals, and persistently enhanced it in socially isolated crayfish. Serotonin receptor agonists had opposing effects: A vertebrate serotonin type 1 receptor agonist inhibited the LG neurons in dominant and subordinate crayfish and had no effect in isolates, whereas a vertebrate serotonin type 2 receptor agonist enhanced the LG neurons' responses in all three types of crayfish. The LG neurons appear to have at least two populations of serotonin receptors that differ in efficacy in dominant, subordinate, and socially isolate crayfish.

Patterns of hormone replacement therapy in a population-based cohort of postmenopausal German women. Changes after HERS II and WHI.

In July 2002, data from the Women's Health Initiative (WHI) trial provided strong evidence for an increased risk of cardiovascular disease with use of combined estrogen plus progestogen in postmenopausal women. These unexpected results triggered a large and ongoing discussion about the role of hormone replacement therapy (HRT). We investigated the frequency of HRT before and after the publications of the WHI trial and the Heart and Estrogen/Progestin Replacement Study II (HERS II) in a population-based random sample of German women aged 45 - 65 years. A total of 8380 women completed a questionnaire on menopausal status, hysterectomy and HRT. 75 % were postmenopausal. Mean age was 56.1 years; mean age of natural menopause 49.9 years; mean duration of postmenopause was 11 years; 27 % of the women had undergone hysterectomy. The percentage of current HRT users dropped by 16 % (35.4 % to 29.8 %, p = 0.004), past users increased from 19.8 % to 23.5 % (p = 0.03). Among current HRT users, the share of combined conjugated estrogen/progestogen decreased by 41 % (p = 0.008). We observed a decreased prevalence of HRT among German women 7 months after publication of the HERS II and WHI results. The decline was, however less pronounced than reported from other countries. The use of conjugated estrogen/gestagen combinations declined disproportionately compared to other formulations.

Age and markers of Leydig cell function, but not of Sertoli cell function predict the success of sperm retrieval in adolescents and adults with Klinefelter's syndrome.

Microsurgical testicular sperm extraction (mTESE), combined with intracytoplasmic sperm injection (ICSI) represents a chance for azoospermic men with Klinefelter's syndrome (KS) to father children. The objective of this study was to identify predictive factors for the success of mTESE from adolescents and adults with KS. The clinical data of 50 late pubertal adolescents (13-19 years) and 85 adult patients (20-61 years) with non-mosaic KS, who underwent mTESE, were analysed with respect to factors, potentially predictive of active spermatogenesis; specifically a history of cryptorchidism, age, testicular volumes, serum levels of LH, FSH, testosterone (T) and estradiol at the time of surgery. Inhibin B, AMH and INSL3 were additionally analysed in the adolescents. A younger age and a near-compensated Leydig cell function were associated with higher success of sperm retrieval via mTESE: In adolescents ≥15-19 years, spermatozoa were retrieved in 45%, compared to 31% in adults; in adolescents aged 13-14 years, spermatozoa were collected in only 10%. Adolescents with an LH ≤17.5 U/L, along with a T level ≥7.5 nmol/L had the best success rate (54%), which fell to 44% with higher LH, whereas those with low T (<7.5 nmol/L), irrespective of LH had no sperm retrieval. In adults with T levels above and LH below these thresholds, the success rate was 51%, falling to 19%, if LH was higher. When T was lower than threshold, the rate was 17%. No association between testicular volumes, serum levels of FSH, Inhibin B, AMH, estradiol and mTESE success was found. A history of cryptorchidism was associated with lower retrieval rates. A window of opportunity for an approximate 50% chance to retrieve spermatozoa via mTESE exists for young, late pubertal KS patients between age 15 and young adulthood, when Leydig cell function is at its best. In these cases, referral to a centre of expertise should be considered.

Treatment strategies for severe oligoasthenoteratozoospermia (OAT) (<0.1 million/mL) patients.

Intracytoplasmic sperm injection (ICSI) using spermatozoa from patients with severe oligoasthenoteratozoospermia is still a challenge. Although spermatozoa are available, lower fertilisation rates as well as compromised pregnancy rates are observed after ICSI. We aimed at identifying respective parameters in the pre-values of ejaculate samples used for couple counselling. The clinical pre-values of 121 patients and their corresponding 228 ICSI cycles performed between 2002 and 2010 were retrospectively analysed. Patients were divided into three groups: (i) group 1 (G1, n = 51) where all patients showed at least once <0.1 million/mL and ICSI was performed using ejaculate alone; (ii) group 2 (G2, n = 14) patients had once <0.1 Mill/mL or azoospermia and a testicular biopsy before start of ICSI; (iii) group 3 (G3, n = 56) patients were azoospermic and directed immediately to testicular sperm extraction (TESE). The pre-values of G2 differed significantly from G1 in terms of volume and motility. Lutenizing hormone (LH) and follicle-stimulating hormone (FSH) values were equal in G1 and G2, but showed significant differences in comparison to G3. Testis volume was significantly higher in G3. In the corresponding ICSI cycles, the percentage of cancelled embryo transfers was highest in G3. We did not find any correlations of hormonal markers or sperm pre-values with the success rates of ICSI. In our patient cohort, spermatozoa retrieved either from ejaculate or testicular biopsies have nearly identical chances in achieving pregnancies. Patients in need of TESE before ICSI have significantly lower sperm counts. However, it is not possible to calculate threshold values as indicator for TESE.

An autoradiographic study of the commissural and ipsilateral hippocampo-dentate projections in the adult rat.

The distribution of the associational and commissural afferents to the inner one-fourth of the molecular layer of the dentate gyrus of the rat, has been studied autoradiographically following small injections of 3H-proline into the hilar region of the dentate (from which both groups of afferents arise). Different patterns of axonal labeling are observed after injections into the temporal (i.e., caudal), middle, or septal (rostral) thirds of the hippocampus. Thus after temporal injections labeled commissural and associational afferents are found only in the caudal third of the dentate gyrus, and the grain densities observed on the two sides are markedly asymmetrical around the short, or transverse, axis of the dentate. On the other hand, injections into the middle third of the hippocampus lead to extensive labeling of the commissural and associational afferents throughout the rostral two-thirds of the dentate gyrus, and their distribution, as judged by grain density estimates, is symmetrical on the two sides. Septal injections label fibers over the rostral half of the dentate, and again the labeling pattern on the two sides is asymmetrical (but in the reverse pattern from that seen after temporal injections). These distinctive patterns in the distribution of the two classes of afferents can generally be accounted for on the following assumptions: (1) the commissural and associational afferents share a common cytochemical specificity; (2) they compete with each other for the limited number of synaptic sites available upon the proximal portions of the granule cells: (3) the granule cells are generated along two distinct morphogenetic gradients:from the temporal to the septal pole of the dentate gyrus, and from the tip of its dorsal (or external) to the tip of its ventral (internal) blade; and (4) the first fibers to arrive monopolize the majority of the available synaptic sites, and those that reach their target field later, synapse predominantly upon the last-formed granule cell dendrites. To this extent our findings are consonant with the "temporal hypothesis" first formulated by Gottlieb and Cowan ('72). However, to account for the restricted distribution of afferents from the temporal part of the hippocampus, it is necessary to further postulate that there is some degree of topographic (or region-to-region) specificity in the ipsilateral and contralateral hippocampo-dentate projections.

An autoradiographic study of the development of the entorhinal and commissural afferents to the dentate gyrus of the rat.

The development of the entorhinal, ipsilateral associational, and commissural afferents to the dentate gyrus have been studied autoradiographically, following the injection of small amounts of tritiated proline into the medial and lateral parts of the entorhinal cortex, and into fields CA3c and CA4 of the hippocampus, in a series of rats, on the third, sixth, and twelfth postnatal days. Clear labeling of the entorhinal afferents were found at the third postnatal day, and from the earliest stage studied the afferents from the two parts of the entorhinal cortex appear to be spatially segregated within the stratum moleculare of the dentate gyrus: the fibers from the lateral entorhinal area occupying the outermost one-third, or so, of this stratum, while those from the medial entorhinal cortex occupy its middle zone. The ipsilateral hippocampo-dentate associational pathway is present at the third postnatal day, but the commissural projection (which shares with it the inner part of the stratum moleculare) could not be labeled until the sixth postnatal day. By the twelfth day the characteristic adult pattern of distribution of the terminals of the two hippocampo-dentate pathways is established. Although this pattern is best accounted for on the basis of a temporal competition for the available synaptic sites on the proximal parts of the dendrites of the granule cells, the spatial segregation of these two fiber systems from those arising in the entorhinal cortex, is probably due to the selective fasciculation of fibers in each group of afferents and to their early cytochemical specificity.

7 alpha-Dehydroxylation of cholic acid by cell extracts of Eubacterium species V.P.I. 12708.

NADH:flavin oxidoreductase and 7 alpha-dehydroxylase were induced 5- and 90-fold, respectively, by cholic acid in cultures of Eubacterium species V.P.I. 12708. Assays of 7 alpha-dehydroxylase activity in the presence of various cofactors revealed that optimal activity was obtained in the presence of NAD+ plus FADH2. The pH optima of 7 alpha-dehydroxylase activity in whole cells and cell extracts were 7.0. The similar induction pattern of these two enzymes and the apparent cofactor requirements for 7 alpha-dehydroxylation suggest a relationship between 7 alpha-dehydroxylase and NADH:flavin oxidoreductase.

Prodrugs of L-cysteine as protective agents against acetaminophen-induced hepatotoxicity. 2-(Polyhydroxyalkyl)- and 2-(polyacetoxyalkyl)thiazolidine-4(R)-carboxylic acids.

Eight prodrugs of L-cysteine (1a-h) were synthesized by the condensation of the sulfhydryl amino acid with naturally occurring aldose monosaccharides containing three, five, and six carbon atoms. The resulting 2-(polyhydroxyalkyl)thiazolidine-4(R)-carboxylic acids (TCAs) are capable of releasing L-cysteine and the sugars by nonenzymatic ring opening and hydrolysis. Thus, when added to rat hepatocyte preparations in vitro, these TCAs (1.0 mM) raised cellular glutathione (GSH) levels 1.2-2.1-fold relative to controls. On the basis of this finding, the cysteine prodrugs were tested as protective agents against acetaminophen-induced hepatotoxicity in a mouse model. The TCA derived from D-ribose and L-cysteine (RibCys, 1d) showed the greatest therapeutic promise of the series, with a 100% (12/12) survival profile compared to 17% without treatment. However, the degree of stimulation of GSH production in rat hepatocytes by these prodrugs did not correlate with the extent of protection afforded in mice, suggesting that pharmacokinetic parameters must supervene in vivo. To evaluate the effect of increased lipid solubility, we prepared prodrugs 2a-c by using peracetylated aldehydic sugars in the condensation reaction. These compounds, however, displayed acute toxicity to mice, possibly due to liberation of the acetylated sugars themselves. Nevertheless, the efficacy of the unacetylated TCAs, and RibCys (1d) in particular, suggests that the prodrug approach for the delivery of L-cysteine to the liver represents a viable means of augmenting existing detoxication mechanisms in protecting cells against xenobiotic substances that are bioactivated to toxic, reactive metabolites.

Development of habituation in the crayfish due to selective weakening of electrical synapses.

During posthatching development, transmission becomes substantially reduced at monosynaptic electrical synapses between tactile afferents and the command neuron for caudal tailflip escape responses of the crayfish. The effectiveness of a parallel disynaptic pathway to the same command neuron is unaltered during posthatching growth. In small crayfish both the monosynaptic and disynaptic sensory pathways can elicit command cell action potentials. At this stage, the characteristics of the tailflip neural circuit are evidently controlled by the shorter latency, non-labile monosynaptic pathway. Consequently, tailflips can be reliably elicited in young crayfish, even at brief (2 s) interstimulus intervals. Tailflip responses of large, older crayfish are known to habituate when tactile stimuli are repeated at intervals up to 5 min. This decline in behavioral responsiveness is presumed to be mediated by low frequency synaptic depression (LFD) at first-order synapses of the disynaptic pathway. The lability of these synapses does not change during post-hatching development. Weakening of the monosynaptic pathway may be caused by command cell growth during posthatching development.

Determination of metalloproteinases, plasminogen-activators and their inhibitors in the synovial fluids of patients with rheumatoid arthritis during chemical synoviorthesis.

The concentrations of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-8 (MMP-8), matrix metalloproteinase-9 (MMP-9), lactoferrin and urokinase plasminogen activator (uPA), tissue-type plasminogen activator (tPA) and the inhibitors, tissue inhibitor of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor-1 (PAI-1), plasminogen activator inhibitor (PAI-2), and alpha2-macroglobulin in the synovial fluids of patients with rheumatoid arthritis was determined before and during chemical synoviorthesis with a sodium salt of the fatty acids from cod-liver oil (Varicocid). Synovial fluids were obtained before treatment from 37 patients with rheumatoid arthritis and, in most cases, at 8 and 24 h after injection of the agent. Well-established ELISAs were used to determine the amounts of all proteins. All patients with rheumatoid arthritis revealed very high levels of metalloproteinases (about 1-15 mu g/ml) in their synovial fluids. During the inflammation inducing treatment the granulocyte enzymes increased. In contrast to this, the level of MMP-1 decreased. All granulocyte-derived enzymes were strongly correlated with each other, whereas their dependence on the granulocyte count was only weak. uPA and PAI-2 showed good correlations with the granulocytes-derived enzymes, but were also only weakly correlating with the cell counts. t-PA was not detected by the ELISA used. The proteases, MMP-8, MMP-9 and uPA were increased 8 h after the treatment, whereas the specific inhibitors TIMP-1, PAI-1 and PAI-2 showed significant changes only 24 h after the injection. Matrix metalloproteinases are important factors in the pathogenesis of rheumatoid arthritis. The inflammatory activity in the joint could be better correlated to the granulocyte enzymes than to the granulocyte counts. The levels of uPA and PAI-2 are also parallel to the granulocyte enzyme levels and might underly the same regulatory mechanism.

Antibacterial properties of bile acid oxazoline compounds.

Chenooxazoline (50-100 microM) inhibited (greater than 50%) both 7 alpha and 7 beta-dehydroxylase activities in whole cells and cell extracts of Eubacterium sp. V.P.I. 12708. Chenooxazoline (greater than or equal to 50 microM) and methylchenooxazoline (greater than 25 microM) but not lithooxazoline (less than or equal to 100 microM) inhibited growing cultures of Eubacterium sp. V.P.I. 12708. Chenooxazoline (100 microM) also inhibited the growth of certain members of the genera Eubacterium, Clostridium, Bacteroides and Staphylococcus but not Pseudomonas, Escherichia, Salmonella or the eucaryotic microorganism, Saccharomyces cerevisiae (less than or equal to 400 microM).

Metabolism of bile acid oxazoline derivatives by hepatocyte monolayer cultures and intestinal anaerobic bacteria.

Certain bile acid oxazoline derivatives (100 microM), but not corresponding unconjugated bile acids (100 microM), were found to inhibit the growth of Eubacterium sp. V.P.I. 12708. The growth inhibition was correlated with the polarity of the steroid portion of the bile acid oxazoline. Primary cultures of adult rat hepatocyte monolayer cultures converted [7 epsilon-14C]methylchenooxazoline3 into MeOH-H2O soluble derivatives. Certain intestinal bacteria were capable of metabolizing [17 epsilon-14C]methylchenooxazoline as well as the MeOH-soluble hepatocyte derivative(s). These results suggest that bile acid oxazoline derivatives may undergo hepatic, as well as bacterial metabolism during enterohepatic circulation.

Bile acid induction specificity of 7 alpha-dehydroxylase activity in an intestinal Eubacterium species.

The addition of cholic acid to growing cultures of Eubacterium species V.P.I. 12708 caused a 25 and 46-fold increase in 7 alpha-dehydroxylation activity using cell extracts or whole cell suspensions, respectively. Bile acid conversion rates using either [14C]-cholic acid or [14C]-chenodeoxycholic acid as substrates increased at approximately the same rate when either cholic or chenodeoxycholic acid was added to growing cultures as inducer. The induction of 7 alpha-dehydroxylase activity was highly specific requiring a free C-24-carboxyl group and an unhindered 7 alpha-hydroxy group on the B ring of the steroid nucleus. Unexpectedly, cholic acid also rapidly induced NADH:flavin oxidoreductase activity in growing cultures of this bacterium.

Peripheral arterial tonometry for the diagnosis of obstructive sleep apnea.

Sleep related breathing disorders have been recognized as a risk factor for cardiovascular disorders. Peripheral arterial tonometry (PAT) allows to monitor vasoconstriction on the finger continuously and non-invasively. We investigated whether the rapid changes of autonomous function can be assessed by PAT. In 21 patients with obstructive sleep apnea and arterial hypertension we recorded PAT in parallel to cardiorespiratory polysomnography and invasive arterial blood pressure. The correlation between periodic PAT attenuations and the total number of apneas (r = 0.656, p < 0.01) and the total number of cortical arousal (r = 0.583, p < 0.01) were significant. The PAT signal cannot substitute blood pressure but allows a good recognition of apneas and subcortical arousal and gives additional information on changes of sympathetic and parasympathetic tone during sleep.