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Biomedical subjects

G Franz

Publications and source records attributed to G Franz.

At least 19 recordsLinked to original sources
PubMed2004

Experimental traumatic brain injury in rats stimulates the expression, production and activity of Alzheimer's disease beta-secretase (BACE-1).

Traumatic brain injury (TBI) is a risk factor for the development of Alzheimer's disease (AD). After a traumatic brain injury depositions of amyloid beta (Abeta) in the brain parenchyma were found. In this study we investigated the expression pattern of beta-secretase (BACE-1) in ipsi- or contralateral hippocampus and cortex following controlled cortical TBI in rats. BACE-1 mRNA levels, estimated by real time RT-PCR, were elevated 24 h post injury, and persisting up to 72 h, in the ipsi- and contralateral hippocampus and cerebral cortex as compared to the sham-treated animals (p<0.01). The TBI-induced changes in BACE-1 mRNA are due to enhanced hippocampal and cortical expression of BACE-1 mRNA in neurons and reactive astrocytes as revealed by in situ hybridization. The alterations in hippocampal BACE-1 mRNA levels are accompanied by corresponding increases in BACE-1 protein levels in ipsi- and contralateral hippocampus and ipsilateral cortex as demonstrated by Western blot analysis. In contrast, in the contralateral cortex only a weak increase of traumatically induced BACE-1 protein production was found. The activity of BACE-1 as measured by the formation of the cleavage product of amyloid beta precursor protein, transiently increased up to 48 h after injury, but returned to basal level 7 days post injury. This study demonstrates that the beta-secretase is stimulated following TBI and may suggest a mechanism for the temporal increase of Abeta levels observed in patients with brain trauma.

Alzheimer Disease↗
PubMed2004

Refractory status epilepticus due to acute hepatic porphyria in a pregnant woman: induced abortion as the sole therapeutic option?

A 22-years old, 55 kg female patient in the twelfth week of pregnancy developed neuropsychiatric syndromes and in the following status epilepticus. Raised porphyrines and porphyrine precursors were found in the patient's urine. Despite intravenous glucose infusions and appropriate medication no reduction in seizure-frequency and neuropsychiatric syndromes was observed. An abortion was induced. After the interruption and starting of haem arginate therapy, seizure activity stopped and porphyrine precursors returned to normal levels, and after 6 weeks the patient was discharged in excellent clinical condition. This report describes a status epilepticus caused by acute hepatic porphyria, triggered by pregnancy, in a 22-years old woman. To our knowledge this is the first report of induced abortion as successful treatment in acute hepatic porphyria induced status epilepticus.

Abortion, Induced↗
PubMed2004

Stability control of valerian ground material and extracts: a new HPLC-method for the routine quantification of valerenic acids and lignans.

A new HPLC-method for the separation of medium polar and nonpolar compounds in preparations of Valeriana officinalis was established for stability control. Powdered valerian root and a commercial ethanolic valerian extract were investigated for apparent differences in stability behaviour. Storage conditions were chosen according to the ICH-guidelines. Changes in composition of valerenic acids and lignans were observed depending on storage conditions and packaging materials. Hydroxyvalerenic acid, pinoresinol and hydroxypinoresinol were identified as degradation products in Valerian root, especially during accelerated testing. Ethanolic extracts appeared not to be as sensitive for chemical degradation under climatic influences compared to the crude plant material, and showed no increase in the amounts of lignan-aglyka. In comparison, extracts showed high sensitivity on changes of physical properties like loss on drying and viscosity.

Chromatography, High Pressure Liquid↗
PubMed2004

HPLC profiling and quantification of active principles in leaves of Hedera helix L.

Ivy (Hedera helix L., Araliaceae), is an evergreen medicinal and ornamental plant. Depending on leaf polymorphism different shaped ivy leaves were extracted and subsequently analyzed by reversed-phase high performance liquid chromatography (RP-HPLC). Quantitative determination of its most prominent saponins hederacoside C (1) and alpha-hederin (2) from different ivy leaf extracts were detected, validated and optimized for quick profiling. The linearity of response, repeatability and reproducibility of the applied RP-HPLC method are reported.

Chromatography, High Pressure Liquid↗
PubMed2003

Amyloid beta 1-42 and tau in cerebrospinal fluid after severe traumatic brain injury.

OBJECTIVE: To determine whether CSF amyloid beta 1-42 (Abeta-42) and tau have predictive value for prognosis after head injury. METHODS: CSF samples were collected from 29 patients with severe head trauma between 1 and 284 days post-trauma. Abeta-42 and tau levels were measured using sandwich ELISA techniques and compared with CSF levels in patients with cognitive disorders and headache. RESULTS: At all time points, concentrations of Abeta-42 were significantly lower in patients with traumatic brain injury (TBI) than in control groups. A significant correlation existed for Abeta-42 levels and outcome of patients. Below a cutoff of 230 pg/mL, the sensitivity of Abeta-42 to discriminate between good outcome (Glasgow Outcome Score 4 and 5) and poor outcome (Glasgow Outcome Score 1 through 3) was 100% at a specificity of 82%. CSF tau levels were significantly higher in patients with TBI than in any control group. In patients with multiple CSF samples collected at various time points between 1 and 32 days after the trauma, tau levels increased early after TBI, peaked in the second week post-trauma, and slowly decreased thereafter. Independent of outcome, all patients had normal tau levels when CSF was collected more than 43 days post-trauma. CONCLUSIONS: Abeta-42 and tau may play a potential role in the pathophysiology of TBI. Furthermore, the results of this study suggest that Abeta-42 may be a supportive early predictor for recovery after severe head injury.

Adolescent↗
PubMed2003

Quality aspects of traditional and industrial Kava-extracts.

An aqueous decoction of Piper methysticum has been used since centuries of Pacific Island at social religious-ceremonial and social events without hepatotoxic side effects in contrast to the speculation on industrial Kava preparations. It was assumed that the traditional non-alcoholic drink contains a spectrum of other constituents compared to the acetonic and ethanolic extracts. The TLC-analysis demonstrates, however, that under qualitative aspects there is no difference between aqueous and acetonic and ethanolic extracts respectively.

Chromatography, Thin Layer↗
PubMed2003

Stability testing on typical flavonoid containing herbal drugs.

The aim of the presented work was to examine possible changes in the flavonoid pattern of common flavonoid containing herbal drugs during long term and stress testing storage periods. HPLC fingerprint was used to demonstrate the differences in stability of individual flavonoid components. In addition, the total flavonoid content was determined according to the pharmacopoeial photometrical method. Drug material was stored according to the ICH-guidelines at 25 degrees C and 60% rh (relative humidity) for long term testing over a 24 months period or at 40 degrees C and 75% rh under stress conditions for 6 months. Increased temperatures of 80 degrees C and 100 degrees C were chosen to elucidate possible instabilities of selected flavonoids. As an overall result, during long term testing, no significant changes in the flavonoid pattern can be detected. However, some flavonoid containing herbal drugs (e.g. birch leaves), showed a decrease of most flavonoids when stored at high temperature by an increase in the respective aglycones. Similar results were obtained during storage at 40 degrees C/75% rh.

Betula↗
PubMed2002

Recombination between homologous autosomes in medfly (Ceratitis capitata) males: type-1 recombination and the implications for the stability of genetic sexing strains.

The sterile insect technique (SIT) is an environmentally safe technology to control insect pests. To improve this technology, genetic sexing strains (GSS) have been developed for the Mediterranean fruit fly, Ceratitis capitata. Such strains are based on Y-autosome translocations linking a selectable marker to the male sex and their long-term stability, especially under large-scale mass rearing conditions, is threatened by genetic recombination in the heterozygous males. We have measured male recombination in order to be able to construct GSS that are more stable. Our results show that male recombination occurs at very low frequencies, that is, below 1% per generation. Furthermore, recombination in medfly males occurs premeiotically. By selecting strains where the Y-autosome translocation breakpoint and the selectable marker are closely linked, the deleterious effects of recombination on the stability of GSS can be minimized. In such strains recombination is reduced by ca. 80% as compared to previously studied GSS. Although recombinants still occur at very low frequencies they still pose a threat to the integrity of the sexing system if they possess a selective advantage. Under mass rearing condition such recombinants will accumulate according to their relative fitness and additional measures, such as improved mass rearing strategies, are required to preserve the accuracy of the sexing system. As a conclusion it is shown that current GSS are stable enough to allow mass rearing at levels exceeding 1000 million male medflies per week.

Animals↗
PubMed2001

Sulfated beta-(1-->4)-galacto-oligosaccharides and their effect on angiogenesis.

Sulfated beta-(1-->4)-galacto-oligosaccharides were prepared from an arabino-galacto-rhamno-galacturonan from Lupinus polyphyllus Lindl. by successive partial hydrolysis and SO3-pyridine sulfation in DMF. The resulting oligosaccharide polysulfates were analyzed by analytical GPC and the sulfate content was determined by ion chromatography. DP 5 and higher showed a pronounced antiangiogenic effect with scores of 0.9-1.2 for DP 7-9 using the CAM-assay. An interaction with the fibroblast growth factor FGF-2 was noticed for DP 4-12 depending on the degree of sulfation using the FGF-2-trypsin assay.

Allantois↗
PubMed2001

Partial synthetic glucan sulfates as potential new antithrombotics: a review.

Structurally defined sulfated polysaccharides were produced by partial synthesis to develop new antithrombotics as potential heparin alternatives. Glucans of different natural origins were used as starting polymers. The resulting glucan sulfates display pronounced anticoagulant effects; some of them are as active as heparin. According to studies on the structure-activity relationships, besides the molecular weight (MW) and the degree of sulfation (DS), the sulfation pattern and the polysaccharide basic structure are crucial parameters for their anticoagulant potency. Their mode of action differs from that of heparin. Depending on their individual structure, they specifically interfere with various stages of the coagulation process. In vivo, they partly exhibit antithrombotic activity similar to that of heparin. But the in vivo efficacy is not just based on their anticoagulant activity. Their profibrinolytic actions and their strong TFPI-releasing effect may considerably contribute to this overall effect. Due to their manifold interactions with the system of hemostasis, each glucan sulfate shows a structure-dependent, individual action profile. From the investigated glucan sulfates, mainly C2- and C4-sulfated, linear beta-1,3-glucan sulfates with DS > 1.0 and MW between 18 and 50 kDa proved to be most suitable for a potential use as heparin alternatives. The results of this study demonstrate the impact of the various structural parameters on the antithrombotic activity of sulfated polysaccharides. However, the biological actions of sulfated polysaccharides are not limited to hemostasis, but they also show manifold modulating effects on other biological systems. Therefore, the approach of using highly sophisticated carbohydrate drug design might be a possibility to obtain new drugs with specific action profiles.

Animals↗
PubMed2001

Hermes-mediated germ-line transformation of the Mediterranean fruit fly Ceratitis capitata.

We report the use of the Hermes transposable element for germ-line transformation of the Mediterranean fruit fly, Ceratitis capitata. Hermes was able to genetically transform this insect at an estimated frequency between 0.6 and 1.1%, which is comparable to the transformation frequencies obtained for this species when using other transposable elements. Hermes integrates into the medfly genome by a cut-and-paste mechanism and the sequences integrated into the genome are delimited by the terminal nucleotides of the Hermes inverted terminal repeats. Integration resulted in the generation of 8 bp target site duplications, the sequences of which conformed to the target site duplications generated by hAT element transposition in insects. The Hermes element is one additional genetic tool that can be deployed in manipulating and characterizing the medfly genome.

Animals↗
PubMed2001

Temporal and spatial profile of caspase 8 expression and proteolysis after experimental traumatic brain injury.

Recent studies have demonstrated that the downstream caspases, such as caspase 3, act as executors of the apoptotic cascade after traumatic brain injury (TBI) in vivo. However, little is known about the involvement of caspases in the initiation phase of apoptosis, and the interaction between these initiator caspases (e.g. caspase 8) and executor caspases after experimental brain injuries in vitro and in vivo. This study investigated the temporal expression and cell subtype distribution of procaspase 8 and cleaved caspase 8 p20 from 1 h to 14 days after cortical impact-induced TBI in rats. Caspase 8 messenger RNA levels, estimated by semiquantitaive RT-PCR, were elevated from 1 h to 72 h in the traumatized cortex. Western blotting revealed increased immunoreactivity for procaspase 8 and the proteolytically active subunit of caspase 8, p20, in the ipsilateral cortex from 6 to 72 h after injury, with a peak at 24 h after TBI. Similar to our previous studies, immunoreactivity for the p18 fragment of activated caspase 3 also increased in the current study from 6 to 72 h after TBI, but peaked at a later timepoint (48 h) as compared with proteolyzed caspase 8 p20. Immunohistologic examinations revealed increased expression of caspase 8 in neurons, astrocytes and oligodendrocytes. Assessment of DNA damage using TUNEL identified caspase 8- and caspase 3-immunopositive cells with apoptotic-like morphology in the cortex ipsilateral to the injury site, and immunohistochemical investigations of caspase 8 and activated caspase 3 revealed expression of both proteases in cortical layers 2-5 after TBI. Quantitative analysis revealed that the number of caspase 8 positive cells exceeds the number of caspase 3 expressing cells up to 24 h after impact injury. In contrast, no evidence of caspase 8 and caspase 3 activation was seen in the ipsilateral hippocampus, contralateral cortex and hippocampus up to 14 days after the impact. Our results provide the first evidence of caspase 8 activation after experimental TBI and suggest that this may occur in neurons, astrocytes and oligodendrocytes. Our findings also suggest a contributory role of caspase 8 activation to caspase 3 mediated apoptotic cell death after experimental TBI in vivo.

Animals↗
PubMed2001

Structurally related immunological effects of triterpenoid saponins.

The influence of the triterpenoid saponins 1-10 has been investigated on murine spleenocytes in the lymphocyte transformation test and on murine macrophages in an phagocytosis assay. The lymphocyte transformation test and the phagocytosis assay showed that the tested compounds have no stimulating effect. However, a significant inhibition of lymphocyte proliferation by the triterpenoid saponins 2, 6 and 10 was demonstrated.

Animals↗
PubMed2000

Characterization of the anticoagulant actions of a semisynthetic curdlan sulfate.

Sulfation of curdlan, a natural, linear beta-1,3-glucan results in potent anticoagulant and antithrombotic agents. The different activity characteristics in the classical coagulation assays were shown to depend on various structural parameters. To obtain more detailed information about their structure-dependent mechanisms of action, one representative of these beta-1,3-glucan sulfates (CurS), was further investigated using several coagulation assays and amidolytic tests with chromogenic substrates. The mode of action of CurS differs from that of heparin. CurS reduces the thrombin formation by principally inhibiting the intrinsic FXa generation. As shown by amidolytic assays, it eliminates already generated thrombin mainly by accelerating the HCII-mediated thrombin inactivation, whereas its AT-mediated anti-thrombin activity is considerably lower than that of heparin. Further, it prevents the thrombin-mediated fibrin polymerization by directly interfering with the thrombin action on fibrinogen as well as by binding to fibrinogen. Finally, CurS is capable to activate the contact system with the consequence of a potential fibrinolytic effect. In conclusion, beta-1,3-glucan sulfates do not inhibit the blood coagulation nonspecifically due to their anionic character, but in dependence on their individual structure, they interfere specifically with the coagulation process at several sites.

Amidohydrolases↗
PubMed2000

The construction of the first balancer chromosome for the Mediterranean fruit fly, Ceratitis capitata.

The construction of the first balancer chromosome, FiM1, for the medfly Ceratitis capitata is described. This chromosome has three overlapping pericentric inversions and is marked with dominant and recessive mutations. The inversion breakpoints of FiM1 suppress recombination throughout the length of the fifth chromosome, allowing lethal mutations to be recovered and maintained. This chromosome will provide a powerful tool for the manipulation of laboratory stocks, in particular, the recovery of new mutant and transgenic strains. We demonstrate the use of FiM1 for the recovery and maintenance of chromosomes carrying lethal mutations.

Animals↗
PubMed2000

Temporal profile and cell subtype distribution of activated caspase-3 following experimental traumatic brain injury.

This study investigated the temporal expression and cell subtype distribution of activated caspase-3 following cortical impact-induced traumatic brain injury in rats. The animals were killed and examined for protein expression of the proteolytically active subunit of caspase-3, p18, at intervals from 6 h to 14 days after injury. In addition, we also investigated the effect of caspase-3 activation on proteolysis of the cytoskeletal protein alpha-spectrin. Increased protein levels of p18 and the caspase-3-specific 120-kDa breakdown product to alpha-spectrin were seen in the cortex ipsilateral to the injury site from 6 to 72 h after the trauma. Immunohistological examinations revealed increased expression of p18 in neurons, astrocytes, and oligodendrocytes from 6 to 72 h following impact injury. In contrast, no evidence of caspase-3 activation was seen in microglia at all time points investigated. Quantitative analysis of caspase-3-positive cells revealed that the number of caspase-3-positive neurons exceeded the number of caspase-3-positive glia cells from 6 to 72 h after injury. Moreover, concurrent assessment of nuclear histopathology using hematoxylin identified p18-immunopositive cells exhibiting apoptotic-like morphological profiles in the cortex ipsilateral to the injury site. In contrast, no evidence of increased p18 expression or alpha-spectrin proteolysis was seen in the ipsilateral hippocampus, contralateral cortex, or hippocampus up to 14 days after the impact. Our results are the first to demonstrate the concurrent expression of activated caspase-3 in different CNS cells after traumatic brain injury in the rat. Our findings also suggest a contributory role of activated caspase-3 in neuronal and glial apoptotic degeneration after experimental TBI in vivo.

Animals↗
PubMed2000

Expression of Fas and Fas ligand after experimental traumatic brain injury in the rat.

Apoptotic cell death plays an important role in the cascade of neuronal degeneration after traumatic brain injury (TBI), but the underlying mechanisms are not fully understood. However, increasing evidence suggests that expression of Fas and its ligand (FasL) could play a major role in mediating apoptotic cell death in acute and chronic neurologic disorders. To further investigate the temporal pattern of Fas and FasL expression after experimental TBI in the rat, male Sprague Dawley rats were subjected to unilateral cortical impact injury. The animals were killed and examined for Fas and FasL protein expression and for immunohistologic analysis at intervals from 15 minutes to 14 days after injury. Increased Fas and FasL immunoreactivity was seen in the cortex ipsilateral to the injury site from 15 minutes to 72 hours after the trauma, respectively. Immunohistologic investigation demonstrated a differential pattern of Fas and FasL expression in the cortex, respectively: increased Fas immunoreactivity was seen in cortical astrocytes and neurons from 15 minutes to 72 hours after the injury. In contrast, increased expression of FasL was seen in cortical neurons, astrocytes, and microglia from 15 minutes to 72 hours after impact injury. Concurrent double-labeling examinations using terminal deoxynucleotidyl transferase-mediated deoxyuridine-biotin nick end labeling identified Fas- and FasL-immunopositive cells with high frequency in the cortex ipsilateral to the injury site. In contrast, there was no evidence of Fas- and FasL-immunopositive cells in the hippocampus ipsilateral to the injury site up to 14 days after the trauma. Further, Fas and FasL immunoreactivity was absent in the contralateral cortex and hippocampus at all time points investigated. These results reveal induction of Fas and FasL expression in the cortex after TBI in the rat. Further, these data implicate an involvement of Fas and FasL in the pathophysiologic mechanism of apoptotic neurodegeneration after TBI. Last, these data suggest that strategies aimed to repress posttraumatic Fas- and FasL-induced apoptosis may open new perspectives for the treatment of TBI.

Animals↗