Occurrence of the giant liver fluke, Fascioloides magna, in sympatric wild ungulates in one area in the Upper Palatinate Forest (northeastern Bavaria, Germany).

Associated with the spreading in (north)western direction of Fascioloides magna from its historic endemic area in Bohemia with its cervid hosts, unusual noticeable hepatic lesions (black-colored tissue, hemorrhage) were observed in deer harvested in hunting grounds and one deer farm located in the Upper Palatinate Forest close to the border to the Czech Republic, initially in the years of 2007 and 2009, respectively. Confirmation of the suspected diagnosis of F. magna infection in October 2011 prompted investigations on the occurrence of "fascioloidosis" among wild ungulates in that locality. From October 2011 to January 2014, livers from 89 cervids and two wild boars were examined for flukes. Thirty-seven livers (40.6%) harbored F. magna: 17 of 21 red deer, nine of 24 sika deer, six of eight fallow deer, four of 36 roe deer, one of two wild boars. Fluke burdens ranged from 2 up to 151 in red deer, from 2 up to 37 in fallow deer, and from 1 up to 7 in sika deer and in roe deer; one fluke was recovered from the liver of one wild boar. No other parasites were recovered from the livers. The rate of recovery of F. magna differed significantly (p < 0.001) among the species of deer (red deer, 81.0%; sika deer, 37.5%; fallow deer, 75.0%; roe deer, 11.1%) and between the age groups (< 1 year: 22.2%, 1 to 2 years: 26.0%, and > 2 years: 70.0%, respectively). There was no association (p > 0.1) between the rate of recovery of F. magna and the sex of the combined 80 deer of ≥ 1 year of age (male: 41.8% and female: 31.4%). The occurrence of F. magna in the wild ungulates in the Upper Palatinate Forest area in northeastern Bavaria is of epidemiological importance for the further spreading of the parasite into Germany with migrating deer.

Competitive polymerase chain reaction used to diagnose cutaneous leishmaniasis in German soldiers infected during military exercises in French Guiana.

A competitive polymerase chain reaction (PCR) followed by enzyme-linked-immunoassay-based verification of PCR products has been developed, which facilitated the diagnosis of leishmaniasis in two German soldiers who underwent survival training in the jungle of French Guiana and returned with therapy-resistant pyoderma-like lesions. After treatment with liposomal amphotericin B, the skin manifestations disappeared, and leishmania DNA could no longer be detected by PCR. In the context of growing military involvement in areas where leishmaniasis is prevalent, this assay may help detect or, due to its internal controls, exclude cases of infection with this parasite.

Cornified envelope formation by anthralin, simple analogues, and related anthracenones.

The ability of the antipsoriatic anthralin to induce HaCaT keratinocyte differentiation was investigated and correlated with its potency to inhibit proliferation of keratinocytes. To determine the structural requirements for this effect, anthralin and seventeen simple analogues or related anthracenones were examined for their ability to induce the formation of cornified envelope as a marker of terminal differentiation. Covalently cross-linked protein was measured as a key feature of this process. Induction of keratinocyte differentiation was significant at a concentration of 0.5 microM anthralin after 48 h exposure. The presence of the 1,8-dihydroxy groups is a critical determinant of cross-linking activity, since removing or exchanging these groups prevented the induction of keratinocyte differentiation. Furthermore, at least one hydrogen atom at the 10-position of anthralin is required. Moreover, anthralin, anthralin dimer, and anthralin triacetate exhibited antiproliferative and antirespiratory activity at concentrations required to induce keratinocyte differentiation, suggesting a causality between these effects. In addition, cornified envelope formation was observed for a number of related anthracenones at concentrations as low as 1-5 microM. In general, compounds containing benzoyl substituents, independent of the position in the anthralin nucleus, were more potent than those having benzyl substituents. Only marginal differences in cross-linking potency were observed within a number of phenylpropionyl substituted analogues, suggesting that the ability to induce keratinocyte differentiation is independent of the nature of substituents at the side chain.

10-Phenylbutyryl-substituted anthracenones as inhibitors of keratinocyte growth and LTB(4) biosynthesis.

A recent observation that phenylbutyryl anthracenone 2, an analogue of the antipsoriatic anthralin, is a potent inhibitor of leukotriene B(4) (LTB(4)) biosynthesis has prompted a search of other anthracenones with improved antiproliferative activity. In that direction, a limited number of analogues related to 2 have been prepared and evaluated in the HaCaT keratinocytes proliferation and in the polymorphonuclear leukocyte LTB(4) assay. The 4-methoxy analogue 2a and the side chain methylated 2l retain the full inhibitory activity of 1 against LTB(4) biosynthesis while their antiproliferative activity is markedly enhanced and comparable to that of the antipsoriatic anthralin. In contrast to anthralin, cytotoxic effects against cell membranes are strongly reduced as documented by the LDH activity released from cytoplasm of keratinocytes.

Antipsoriatic anthrones with modulated redox properties. 5. Potent inhibition of human keratinocyte growth, induction of keratinocyte differentiation, and reduced membrane damage by novel 10-arylacetyl-1,8-dihydroxy-9(10H)-anthracenones.

The synthesis and structure-activity relationships (SARs) of a series of novel 10-arylacetyl-1,8-dihydroxy-9(10H)-anthracenones are described. Acylation of anthralin with either the appropriate arylacetyl chlorides or arylacetic acids in the presence of pyridine or via the coupling agent dicyclohexylcarbodiimide (DCC), respectively, furnished this structural class of antipsoriatic agents. Potential antipsoriatic activity was evaluated in complementary assays specifically addressed to three important aspects of psoriasis. First, several compounds were identified which are equally potent as inhibitors of human keratinocyte growth as the antipsoriatic agent anthralin. Furthermore, improved ratio of antiproliferative activity to cytotoxicity is demonstrated by the reduced potential of the novel analogues to induce membrane damage, which is a benefit of their reduced ability to generate oxygen radicals as documented by deoxyribose degradation. Second, analogue 3o bearing a hydroxamate functional group was also a highly potent inhibitor of LTB(4) biosynthesis in addition to its excellent antiproliferative activity. SARs of these inhibitors of both keratinocyte growth and LTB(4) biosynthesis with respect to the nature of the para-substitution in the 10-phenylacetyl side chain are discussed. Third, the compounds were also evaluated for their ability to induce the formation of cornified envelope protein in keratinocytes. Cross-linking of cellular protein as a marker of terminal differentiation of keratinocytes was observed for many 10-arylacetyl analogues at concentrations required to arrest cell growth. This newly uncovered activity of the novel anthracenones suggests antipsoriatic potential with respect to disturbance of keratinocyte differentiation, in addition to hyperproliferative and inflammatory aspects of psoriasis.

Heterocyclic substituted anthralin derivatives as inhibitors of keratinocyte growth and inducers of differentiation.

Heterocyclic substituted derivatives of the antipsoriatic anthralin were synthesized and evaluated in vitro for their antiproliferative action against keratinocytes and their ability to induce keratinocyte differentiation. The indole-2-carboxylic acid analogue 2e exhibited the same excellent antiproliferative activity as anthralin and also induced terminal differentiation of keratinocytes. As a benefit of its strongly diminished potential to generate oxygen radicals, 2e did not induce damage of keratinocyte membranes.

[Cerebellar hemorrhage and cerebellar infarct: retrospective study of 125 cases]. / Kleinhirnblutungen und Kleinhirninfarkte: retrospektive Studie von 125 Fällen.

In a retrospective study of 125 patients, symptoms, diagnosis, and clinical course of 64 cases of cerebellar infarction and 61 cerebellar hemorrhage were studied retrospectively. Neurologically, cerebellar signs were present in 50% of hemorrhages and 7%, of infarctions, while 50% of patients with cerebellar hemorrhage and 37% of patients with cerebellar infarction showed brain stem symptoms or cranial nerve deficits; at least slight disturbance of consciousness was present in all patients. The state of consciousness, as estimated by the Innsbruck Coma Scale, together with diagnostic imaging (CT and/or MRT) allowed precise indication for surgical intervention. Over-all lethality was 11% for cerebellar infarction, and 31%, for cerebellar hemorrhage. Comparison of clinical outcome and state of consciousness at time of surgery suggests, that decompressive craniotomy should be performed even in deeply comatose patients with signs of decerebration.

Time course of cerebral blood flow velocity in central nervous system infections. A transcranial Doppler sonography study.

In a 3-year period, 110 patients with central nervous system infections of various causes were examined serially by means of transcranial Doppler sonography. In viral-induced infections, no changes of flow velocity in basal cerebral arteries were seen, whereas in bacterial meningitis, a significant increase of blood flow velocity in the middle cerebral artery was recorded. Its extent was mainly associated with the type of the infectious agent, most frequently observed in pneumococcal meningitis (77%). The increase was up to 100% of the baseline values and was reversible in all cases. All patients were offered full-scale neurointensive care, and all subjects with bacterial meningitis were fully heparinized.

[Peri-articular calcinosis after craniocerebral trauma--the natural course and treatment concepts]. / Die periartikulären Verkalkungen bei Zustand nach Schädel-Hirn-Trauma--der natürliche Verlauf und Behandlungskonzepte.

Occurrence of periarticular ossification (PAO) is a serious complication in the rehabilitation of patients with neurological diseases, especially those with severe head injuries. The present concept for operative intervention in PAO postulates late surgical treatment after "maturation" of these heterotopic ossifications, because of a suspected higher rate of reoccurrence after early removal. In a retrospective analysis of nine arthrolysis in six patients with neurological diseases suffering from PAO (five patients with traumatic apallic syndrome and one patient with spontaneous subarachnoidal haemorrhage), the validity of a new concept of treatment of primary neurological diseases was investigated. Because of the well-known secondary and tertiary problems (fibrotic stiffness, osteoporosis, compression syndrome of peripheral nerves, muscle atrophy), we chose early removal of the ossifications. Our results demonstrate that the former concept of surgical intervention in "mature PAO" only can no longer be recommended as superior to early surgical treatment in neurological diseases, particularly in patients with traumatic apallic syndrome associated with PAO.