Environmental determinants on the assemblage structure of Drosophilidae flies in a temperate-subtropical region.

The species composition and the relative abundance of species in an insect community can vary in time and space for many reasons, including climatic variables and habitat preferences. Drosophilids were collected each quarter from April 2011 to April 2012 (five collections in all) in a natural area of the Pampa biome, considering three environments: open field, forest edge and the interior of forest patches. Kruskal-Wallis and chi-square tests were used to examine the effects of temporal and spatial components on the drosophilid assemblage. Four diversity measures: S obs , S rar , H' and E var were used to evaluate the community structure. A total of 7164 drosophilids belonging to 51 species were collected. The interaction of species in each environment varied among sampling periods. The abundance of both Neotropical and exotic species was affected by temporal and spatial components. The species of the D. repleta group were predominantly more abundant in the open field, but they migrated to the forest patches during periods of thermal stress. Generally, diversity was greatest in the interior of forest patches. Nevertheless, temporal components appear to be the predominant environmental determinant of the characteristics of the drosophilid community of the Pampas. Furthermore, the forest patches appear to act as a center of recolonization, reinforcing their importance in the maintenance of biodiversity in the Pampas; this function will be even more important in the future, when the temperatures will, most likely, be higher.

Population dynamics of drosophilids in the pampa biome in response to temperature.

Environmental variables such as temperature and rainfall can directly affect the community structure of dipterans. Seasonal oscillations in the abundance of species of Drosophilidae reflect differences in how tolerant populations are to climatic conditions. Over a period of 14 months, we collected samples in two habitats in the Pampa biome in the municipality of São Luiz Gonzaga, state of Rio Grande do Sul, Brazil (28°24'28″S, 54°57'39″W). The influence of environmental variables on populations of Drosophilidae was evaluated for both collecting sites by using correlation analysis. The results suggested a negative correlation between the abundances of Drosophila cardinoides Dobzhansky & Pavan, Drosophila maculifrons Duda, Drosophila melanogaster Meigen, Drosophila nigricruria Patterson & Mainland, and Zygothrica vittimaculosa Burla with temperature, which is reflected in the distribution of these species within Brazil. Our findings are important for characterizing and preserving biodiversity in this almost-unknown biome in southern Brazil given the current climate change scenario.

Drosophilid assemblages at different urbanization levels in the city of Porto Alegre, state of Rio Grande do Sul, southern Brazil.

The present study analyzed the drosophilid assemblages in different levels of urbanization in the city of Porto Alegre, Rio Grande do Sul, Brazil. Collections were carried out in 2008 in three different environments: a highly urbanized area-"Jardim Botânico," a forested area with intermediary urbanization-"Parque Gabriel Knijnik," and in a relatively well-preserved forested area, although threatened by the urban growth-"Morro Santana." In Jardim Botânico, 36 species belonging to four genera were found, with high abundance of exotic species as Drosophila simulans Sturtevant and Zaprionus indianus (Gupta). In Parque Gabriel Knijnik, 33 species that belonged to four genera were found, with higher abundances of native species belonging to the Drosophila tripunctata species group and Drosophila willistoni species subgroup, and lower abundance of exotic species. As for Morro Santana, 32 species and three genera were found, with higher abundances of native groups, low representativeness of exotic species, and absence of Zaprionus indianus. The analysis of the Jaccard index showed higher similarity in the species composition between samples collected in summer and autumn, and between samples collected in winter and spring. On the other hand, the Morisita index differentiated Jardim Botânico from the other two studied sites. Our results show that Morro Santana is an important area of native biodiversity, reinforcing, therefore, the inclusion of this area in the project for the creation of an ecological corridor as proposed by the Ministry of the Environment of Brazil.

Toxicity of green tea extracts and their constituents in rat hepatocytes in primary culture.

Recent reports on sporadic cases of liver disorders (acute hepatitis, icterus, hepatocellular necrosis) after ingestion of dietary supplements based on hydro-alcoholic extracts from green tea leaves led to restrictions of the marketing of such products in certain countries of the EU. Since green tea is considered to exert a number of beneficial health effects, and, therefore, green tea products are widely used as dietary supplements, we were interested in the possible mechanism of hepatotoxicity of green tea extracts and in the components involved in such effects. Seven hours after seeding on collagen, rat hepatocytes in primary culture were treated with various hydro-alcoholic green tea extracts (two different native 80% ethanolic dry extracts and an 80% ethanolic dry extract cleared from lipophilic compounds). Cells were washed, and reduction of resazurin, used as a viability parameter monitoring intact mitochondrial function, was determined. It was found that all seven green tea extracts examined enhanced resazurin reduction significantly at a concentration range of 100-500 microg/ml medium, while a significant decrease was observed at 1-3mg/ml medium. Decreased levels were concomitant with abundant necrosis as observed by microscopic inspection of the cultures and with increased leakage of lactate dehydrogenase activity from the cells. In a separate series of experiments, the green tea constituents (-)-epicatechin, (-)-epigallocatechin-3-gallate, caffeine and theanine were tested at concentrations reflecting their levels in a typical green tea extract. Synthetic (+)-epigallocatechin (200 microM) was used for comparison. Cytotoxicity was found with (-)-epigallocatechin-3-gallate only. The concomitant addition of 0.25 mM ascorbate/0.05 mM alpha-tocopherol had no influence on cytotoxicity. In conclusion, our results suggest that high concentrations of green tea extract can exert acute toxicity in rat liver cells. (-)-Epigallocatechin-3-gallate seems to be a key constituent responsible for this effect. The relatively low bioavailability of catechins reported after oral exposure to green tea argues, however, against a causal role of these constituents in the reported liver disorders.

Tumor promoters as inhibitors of apoptosis in rat hepatocytes.

Multistage carcinogenesis in rat liver is widely used as an experimental model for the study of the critical events in tumor promotion. After an initial treatment with a genotoxic liver carcinogen ('initiation'), subsequent application of certain non-genotoxic agents can lead to the clonal expansion of putative preneoplastic cells ('promotion'). Obviously, the expansion of these clones is correlated with an increased occurrence of benign and malignant liver tumors at later time points. Since both proliferation and apoptosis were reported to be enhanced in putative preneoplastic liver foci, inhibition of apoptosis was suggested to play a critical role in tumor promotion. In rat hepatocytes in primary culture, the liver tumor promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibited apoptosis initiated by treatment of the cultures with UV irradiation but did not affect apoptosis in non-irradiated cultures. The suppression of apoptosis with TCDD coincided with an attenuated increase of the tumor suppressor protein p53 observed upon UV irradiation. Furthermore, TCDD treatment resulted in a marked hyperphosphorylation of p53. The fact that almost identical concentration-response curves were obtained for the phosphorylation of p53 and the induction of cytochrome P450(CYP)1A-catalyzed 7-ethoxyresorufin O-deethylase (EROD) activity indicates that p53 phosphorylation after TCDD treatment is mediated by the aryl hydrocarbon receptor (AhR) signaling cascade. With tumor-promoting 'non-dioxin-like' polychlorinated biphenyls inhibition of UV-induced apoptosis was also observed. A comparative study investigating the effects of various concentrations did not reveal, however, a clear correlation between the suppression of apoptosis and the induction of CYP2B-catalyzed 7-pentoxyresorufin O-dealkylase (PROD) activity. In summary, inhibition of UV-induced apoptosis with liver tumor promoters is observed in rat hepatocytes in culture. Hyperphosphorylation of key proteins of apoptosis including p53 seems to play a role in this effect.

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

[European Association of Urology guidelines on urinary and male genital tract infections]. / Synoptische Leitlinie der sexuell übertragbaren Erkrankungen (STD) mit Primärsymptomen im männlichen Genitale (S1). Leitinien der Deutschen Gesellschaft für Urologie.

Today, the classical bacteria that cause venereal diseases, e.g. gonorrhea, syphilis, chancroid and inguinal granuloma, only account for a small proportion of all known sexually transmitted diseases (STDs). Other bacteria and viruses as well as yeasts, protozoa and epizoa must also be regarded as causative organisms of STD. Taken together, all sexually transmitted infections comprise more than 30 relevant STD pathogens. However, not all pathogens that can be sexually transmitted manifest diseases in the genitals and not all infections of the genitals are exclusively sexually transmitted. Concise information and tables summarising the diagnostic and therapeutic management of STDs in the field of urology allow a synoptic overview, and are in agreement with the recent international guidelines of other specialist areas. Special considerations (i.e. HIV infection, pregnancy, infants, allergy) and recommended regimens are presented.

Inhibition of apoptosis in rat hepatocytes treated with 'non-dioxin-like' polychlorinated biphenyls.

Polychlorinated biphenyls (PCBs) are among the most prominent persistent environmental pollutants exhibiting neurotoxic, teratogenic and tumour-promoting effects in experimental animals. 'Dioxin-like' properties have been assigned to a number of PCBs whereas other PCBs have been classified as 'non-dioxin-like'. Many of the latter congeners are inducers of cytochrome P450 (CYP) 2B1 and 2B2 similar to the liver tumour promoter phenobarbital. In contrast, 'dioxin-like' PCBs induce CYP1A isozymes, and other congeners have been classified as 'mixed-type' inducers. Inhibition of apoptosis of pre-neoplastic hepatocytes is thought to play a central role in tumour promotion in rat liver. We have used the inhibition of UV-induced apoptosis in rat hepatocytes in primary culture as an in vitro model for mechanistic studies on the inhibition of apoptosis. It could be shown that phenobarbital, and the 'non-dioxin-like' PCBs 28, 101 and 187 completely inhibit UV-induced apoptosis. The concentration-response curves and EC(50) values for this effect, however, were different from those of induction of CYP2B1/2B2-catalysed 7-pentoxyresorufine O-dealkylase or CYP1A-catalysed 7-ethoxyresorufine O-deethylase activities. The PCBs and phenobarbital did not affect the spontaneous incidence of apoptotic nuclei. In conclusion, 'non-dioxin-like' PCBs are likely to promote liver carcinogenesis via the suppression of apoptosis. The signaling events in rat hepatocytes leading to induction of 2B1/2B2 activity by the compounds investigated are assumed to differ from those leading to inhibition of apoptosis.

Inducing effects of dioxin-like polychlorinated biphenyls on CYP1A in the human hepatoblastoma cell line HepG2, the rat hepatoma cell line H4IIE, and rat primary hepatocytes: comparison of relative potencies.

Polychlorinated biphenyls (PCBs) are a group of widespread environmental pollutants. Some non-ortho-substituted congeners with a high likelihood of coplanarity of both aromatic rings have been shown to act like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as agonists of the aryl hydrocarbon receptor (AhR) subsequently leading to adverse effects, such as immunosuppression and tumor promotion. Although there is a broad base of experimental data concerning the toxicity of PCBs in laboratory animals and animal-derived primary cells and cell lines, only few experimental data are available for cells of human origin. As a parameter of AhR activation, induction of CYP1A-mediated 7-ethoxyresorufin O-deethylase (EROD) activity was determined in the human hepatoblastoma cell line HepG2 treated with the PCBs IUPAC Nos. 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189, and with TCDD as a positive control. Compared with results in rat primary hepatocytes and the rat hepatoma cell line H4IIE, treated HepG2 cells showed lower specific EROD activities maximally inducible by TCDD and PCBs, and EC50 values were shifted to higher concentrations. Furthermore, relative potency factors (REPs) for some congeners such as PCBs 81, 126, and 169 greatly differed from those observed in cells derived from rats. Northern blot analyses showed that EROD activities run parallel to changes in CYP1A-specific mRNA contents. The considerable differences in EROD-derived REPs between cells of human and rat origin indicate the need for further investigations in experimental models from different species including humans in order to extend the database of biochemical and toxic responses to PCBs.

Malassezin--A novel agonist of the arylhydrocarbon receptor from the yeast Malassezia furfur.

The yeast Malassezia furfur converts tryptophan into several indole compounds. One of these, malassezin, was identified as 2-(1H-indol-3-ylmethyl)-1H-indole-3-carbaldehyde (1). It was synthesized from N-Boc-indole-3-carbaldehyde in five steps with 12% overall yield. The compound easily cyclizes to indolo[3,2-b]carbazole (7) which is known to interact with the arylhydrocarbon receptor (AHR). Similarly, malassezin was found to induce cytochrome P450 as an agonist of AHR (EC50 = 1.57 microM) in rat hepatocytes.

Potency of various polycyclic aromatic hydrocarbons as inducers of CYP1A1 in rat hepatocyte cultures.

A number of highly toxic environmental pollutants including certain polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), and 'dioxin-like' polychlorinated biphenyls (PCB) are among the most potent agonists of the aryl hydrocarbon receptor (AHR). Induction of cytochrome P4501A1 (CYP1A1) in mammalian cell culture is widely used as a functional parameter for AHR activation providing an estimate for 'dioxin-like' inducing equivalents in extracts from environmental samples. Since a number of polycyclic aromatic hydrocarbons (PAHs) also act as AHR-agonists, the CYP1A1-inducing potencies, measured as induction of 7-ethoxyresorufin O-deethylase (EROD) activity in rat hepatocyte cultures were analyzed for 16 PAHs frequently present in environmental samples. Among these, seven PAHs including benzo[a]pyrene were relatively potent inducers allowing the determination of Induction Equivalency Factors (IEF). For three PAHs including benzo[k]fluoranthene which acted as weak inducers, IEFs were estimated, while six PAHs including acenaphthylene were classified as inactive. Based on different efficacies the concentration-response characteristics of CYP1A1 induction were analyzed in more detail for benzo[a]pyrene, benzo[k]fluoranthene, and acenaphthylene. Benzo[k]fluoranthene was markedly less effective than benzo[a]pyrene as inducer of EROD activity but even more effective than benzo[a]pyrene as inducer of CYP1A1 protein and mRNA. Acenaphthylene was highly more effective on the level of mRNA than on the levels of protein or EROD activity. Further analysis revealed that the low efficacy of acenaphthylene as inducer of CYP1A1 protein and EROD activity is due to its marked cytotoxicity while no clear-cut explanation was found for the differences in efficacy between benzo[k]fluoranthene and benzo[a]pyrene. The EROD-inducing potency of a mixture of 16 PAH was about 2-fold higher than that calculated on the basis of IEFs of the individual constituents of the mixture.

Metabolic degradation, inducing potency, and metabolites of fluorinated and chlorinated-fluorinated dibenzodioxins and dibenzofurans.

The metabolic degradation of fluorinated, chlorinated-fluorinated and chlorinated congeners was measured in liver homogenate of NMRI mice. While in the time period between 0 and 240 min no degradation of the 2,3,7,8-TCDD/TCDF could be detected, for all fluorinated congeners a perceptible degradation was found, even for the 2,3,7,8-TFDD. Stepwise chlorination of the 2,3,7,8-fluorinated congeners leads to a decrease of the degradation rate. In the EROD test, the exchange of chloro- with fluorosubstituents in the 2,3,7,8-TCDF leads to a decrease of induction potency. 3,7-Dichloro-2,8-difluorodibenzofuran was about 1/1000th as potent as 2,3,7,8-TCDF, while 2,3,7,8-TFDF was complete inactive. Comparison of the metabolic rates of different TCDD with those of the analogous TFDD demonstrates that the order of enzymatic degradation of different TCDD and the analogous TFDD is identical. The TFDD are degraded slightly faster than the corresponding TCDD. Surprisingly 1,4,6,9-TXDD showed the second slowest metabolic rate of the fluorinated and chlorinated TXDD after 2,3,7,8-TXDD although none of the 2,3,7,8-positions were substituted. Judging from 2,3,7,8-TFDD and 1,7-dichloro-2,8-difluorodibenzofuran the metabolic pathway of fluorinated and chlorinated-fluorinated congeners seem to be comparable to the chlorinated congeners.

[Animal experiments for testing a hydroxyapatite ceramic coating under vacuum conditions]. / Tierexperimentelle Testung einer unter Niederdruckbedingungen gespritzten Hydroxylapatitkeramikbeschichtung.

Implants that were coated with hydroxyapatite ceramic (H-A.C.) under atmospheric condition in vivo often showed local areas of delamination. By applying the H-A.C. coating using the vacuum plasma spraying (VPS) technique, the mechanical characteristics of the coating was decidedly improved. We used a standardized rabbit model to compare a coating produced by this new technique with an implant conventionally plasma sprayed under atmospheric condition (APS). Cylindrical implants, 6 x 4 mm in size with a region flattened to a depth of 800 microns, were inserted into distal rabbit femurs underneath the patella. The flattened surfaces were coated with either a 150-micron APS-H-A.C. layer or a 150-micron VPS-H-A.C. layer plasma sprayed on an underlying 50-micron porous titanium layer. The animals were killed after 84 or 365 days. After 84 days histomorphologic evaluation revealed that more than 86% of each surface was covered with mature bone, while the VPS-H-A.C. coating demonstrated an almost two times greater tensile strength than the APS-H-A.C. coating. After 365 days both coatings showed a bony coverage of more than 94%. Again the tensile strength testing revealed much higher values for the VPS-H-A.C. coating. This study demonstrates that after 84 days as well as after 365 days in vivo, the VPS-H-A.C. coating had a significantly greater load capacity than an H-A.C. coating applied under atmospheric condition, and an equal affinity for bone.

2,3,7,8-Tetrafluorodibenzo-p-dioxin: a potent agonist of the murine dioxin receptor.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related polychlorinated aromatic hydrocarbons exert a pattern of toxicity related to their binding to a common receptor, the Ah (aryl hydrocarbon) or dioxin receptor. No information is available, however, on the toxicological properties of 2,3,7,8-tetrafluorodibenzo-p-dioxin (TFDD). In our experiments, TFDD was found to act as a highly potent dioxin receptor agonist leading to a transient induction of cytochrome P450(CYP)1A1 mRNA and protein in receptor-proficient mouse Hepa-1 hepatoma cells treated with 10(-10) M TFDD. However, no significant induction of 7-ethoxyresorufin O-deethylase (EROD) activity was observable in TFDD-treated Hepa-1 cells or mouse hepatocytes in primary culture, suggesting an interference with the catalytic activity of CYP1A1. Parallel experiments with 10(-10) M TCDD showed a sustained induction of CYP1A1 mRNA and protein, and of EROD activity. When a reporter gene construct comprising a xenobiotic-responsive element (XRE) in 5'-position was transfected in Hepa-1c-1c-7 cells, 5×10(-8) M TFDD and 5×10(-9) M TCDD induced transcription to a comparable extent. Both inducers were inactive when a mutant XRE with a guanine replaced by thymine was transfected. In metabolism studies in mouse liver homogenate, TFDD was rapidly degraded in the presence of an NADPH-regenerating system, and metabolism was enhanced in liver homogenate from ß-naphthoflavone-pretreated mice indicating that TFDD is metabolized in a CYP-catalyzed pathway. The open ring products dihydroxytetrafluororbiphenyl ether, and 1,2-difluoro-o-benzoquinone, probably derived from 1,2-difluorocatechol, were identified by GC-MS analysis of the incubation mixtures, whereas no phenolic metabolites/and or metabolites with an intact dioxin ring could be found. It is concluded that TFDD, in contrast to its chlorinated analogue, is metabolically unstable, and thus currently does not fulfill the criteria for the recommendation of a TCDD or toxicity equivalency factor (TEF).

Influence of vessel dilatation on restenosis after successful percutaneous transluminal coronary angioplasty.

The aim of this study was to evaluate the influence of vessel dilation on restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) on the basis of quantitative angiographic analysis. To have the best comparison possible, we restrospectively studied a homogenous series of patients from the early 1980s treated according to a standardized PTCA procedure. The study group consisted of 86 patients with stable angina pectoris and single-vessel disease, all of whom underwent successful PTCA for a short concentric lesion in proximal vessel parts. The overall restenosis rate was 27%. Angiographically measured balloon size remained below specifications. The size of the inflated balloon at the site of minimal lumen diameter averaged 2.6 +/- 0.5 mm, and nominal balloon size was 3.3 +/- 0.4 mm (p < 0.001). In 22 patients with an oversized balloon (mean balloon/artery ratio 1.1 +/- 0.16) the restenosis rate was 5% compared with 34% in the corresponding group (p = 0.02). Minimal lumen diameters that were similar after the procedure (2.4 +/- 0.3 vs 2.3 +/- 0.4, NS) were 2.3 +/- 0.4 mm and 1.8 +/- 0.7 mm, respectively, at follow-up (p = 0.002). Multivariate analysis revealed balloon/vessel size ratio (p < 0.001), postprocedure diameter stenosis (p = 0.02), and percentage diameter increase produced by PTCA (p = 0.04) as independent correlates of the late outcome. Postangioplasty minimal lumen diameter was not related to restenosis. The strongest and most significant predictor of late PTCA outcome both by univariate and multivariate analysis was balloon/vessel size ratio, especially when balloon expansion at the site of minimal lumen diameter was regarded. In patients with continued success at follow-up, the ratio was 0.81 +/- 0.15 compared with 0.60 +/- 0.11 in patients with restenosis (p < 0.001). Our results suggest that the late angiographic outcome of PTCA is strongly influenced by procedural factors. It appears that in a selected group of patients, an increased balloon/artery ratio, supposedly associated with increased vessel wall stretch, favorably affects the restenosis process.

Healing of apical periodontitis in dogs after apicoectomy and retrofilling with various filling materials.

OBJECTIVE: To histologically assess the efficacy of various retrofilling materials in apical surgery. STUDY DESIGN: The pulps of mandibular premolars in seven beagle dogs were infected; this resulted in periapical lesions. Apical surgery was performed without disinfection of the root canals. Super EBA (Harry J. Bosworth Co., Skokie, III.), two formulations of glass ionomer cement, amalgam with varnish, IRM,(Caulk Co., Ltd., Densply International, Milford, Del.) and a light-cured composite resin were the retrofilling materials used. Roots infected and apicoectomized without retrofilling were positive controls. After 6 months the dogs were killed. The experimental roots and surrounding apical tissues were prepared and histologically examined and relative percentages of bone and inflammation were calculated. RESULTS: Super EBA was consistently the best. In overall periapical condition, Super EBA was statistically superior to all materials except IRM. IRM was superior to the glass ionomer cements but not the other materials. As to percentage of bone, Super EBA was the best overall; it was superior to glass ionomer, composite resin, and the positive control but not different from amalgam or IRM. When comparing remaining numbers of inflammatory cells, Super EBA was superior with the lowest number of inflammatory cells present. CONCLUSION: Although not statistically different from IRM, Super EBA was consistently the best retrofilling material tested when compared with all retrofilling materials studied.

Osteoplastic frontal sinusotomy and extradural microsurgical repair of frontobasal cerebrospinal fluid fistulas.

The choice of the surgical approach and operative technique for the management of cerebrospinal fluid (CSF) fistulas of the anterior cranial fossa are still a controversially discussed topic. Although "extracranial" approaches through the paranasal sinuses are becoming increasingly more popular among otolaryngologists and maxillo-facial surgeons, most neurosurgeons traditionally prefer the "intracranial" repair of CSF fistulas by a craniotomy. We present an approach through the frontal sinus for the repair of dural defects behind the posterior wall of the frontal sinus and at the floor of the anterior cranial fossa. The operative procedure comprises the following main steps: 1) exposure of the anterior wall of the frontal sinus by a bicoronal incision; 2) excision of the anterior wall without frontal burr holes; 3) bilateral removal of the posterior wall of the frontal sinus; 4) extradural inspection of the dura behind the frontal sinus and above the cribriform plate, ethmoidal roof, and orbital roof bilaterally; 5) closure of dural tears by direct suture and a periosteal graft; 6) reinsertion of the anterior wall of the frontal sinus and fixation with titanium micro plates. Twenty-five patients operated upon using this technique are described. The aetiology of the frontobasal lesion was traumatic in 23, and an ethmoid carcinoma in two. In all patients, the dural fistulas were successfully repaired during the initial procedure. One patient died from sudden circulatory arrest after an uneventful postoperative course of nine days. Otherwise, there were no postoperative complications. This technique affords atraumatic extradural inspection and repair of dural fistulas bilaterally behind the frontal sinus, and above the cribriform plate and the ethmoidal and orbital roofs with none or minimal brain retraction. It therefore allows early repair of CSF fistulas also in patients with severe brain injury. Although we consider the extradural closure of fistulas the method of choice, this approach also allows for a combined extradural-intradural procedure, thus enabling the surgeon to treat associated intradural pathologies, such as traumatic lesions or tumours of the frontal cranial base.

CYP1A1-inducing potency in H4IIE cells and chemical composition of technical mixtures of polychlorinated biphenyls.

Polychlorinated biphenyls (PCBs) are present in environmental and tissue samples as complex mixtures of dioxin-like and non-dioxin-like congeners. Induction of cytochrome (CYP) P4501A1-catalyzed 7-ethoxyresorufin-O-deethylase (EROD) activity in H4IIE hepatoma cells is widely used as a simple in vitro bioassay for the dioxin receptor-mediated biological action of dioxin-like agonists. Since the results of the assay may be influenced indirectly by abundant non-dioxin-like PCBs, its application to the bioanalysis of complex PCB mixtures was studied. In the PCB mixtures Arochlor 1254 and Clophen A50, potent dioxin-like non-ortho PCBs and polychlorinated dibenzofurans (PCDFs) were found in minor amounts. However, the non-ortho PCBs accounted for most of the overall 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents based on EROD induction (EROD-TEQs). A comparison with a pattern of toxic equivalents (TEQs) based on toxic equivalency factors (I-TEFs) recently suggested in an international report revealed a much higher relative impact of mono-ortho PCBs on I-TEQs than on EROD-TEQs while total EROD-TEQs approximately coincided with total I-TEQs. It is concluded that the H4IIE bioassay is useful to assess total I-TEQs but does not reflect the individual contributions of PCB subgroups because of a higher evaluation of mono-ortho and di-ortho PCBs by I-TEFs. Based on individual EROD-TEFs, slightly higher mean EROD-TEQs than those calculated by assuming additive behaviour of single PCBs were obtained. This finding suggests a minor synergistic influence of non-dioxin-like PCBs on the inducing potency of dioxin-like agonists in the H4IIE bioassay.

Treatment of exposed implant threads using a synthetic bone graft.

The aim of this study was to evaluate clinically and histologically the use of a synthetic bone graft (Ionogran) alone and in combination with guided bone regeneration (GBR) to facilitate bone regeneration and augmentation around exposed implant threads. Five male Beagle dogs were used in this investigation. Prior to the study all 3rd and 4th premolars were extracted. After 3 months, a flap was elevated and two Brånemark implants were inserted in each quadrant in such a way that two-three threads remained exposed over the alveolar bone. On the control sites the synthetic bone graft was then placed around the exposed threads and the flaps were repositioned and sutured. On the test sites, the same procedure was performed, but an expanded polytetrafluoroethylene barrier was placed to cover the bone graft and implants. Three months after implant placement, the barriers on the test sites were removed, healing abutments were inserted on all implants, and a thrice weekly plaque control regime was initiated. The following clinical parameters were measured at 1, 2, and 3 months: Plaque Index, Gingival Index, Probing Depth and Clinical Attachment Level. Three months after abutment connection the animals were killed and specimens were obtained for histological evaluation. Clinical parameters revealed a significant improvement on the experimental sites compared to control sites during the 3 month loading phase. Histological analyses, however, could not determine a difference in the nature of the implant/tissue interphase between experimental and control sites.

Potency of mixtures of polychlorinated biphenyls as inducers of dioxin receptor-regulated CYP1A activity in rat hepatocytes and H4IIE cells.

Among the polychlorinated biphenyls (PCBs), a family of widespread environmental pollutants, the most toxic non-ortho-substituted coplanar (non-ortho coplanar) congeners are thought to act as strong dioxin (aryl hydrocarbon) receptor agonists leading to adverse effects, such as body weight loss, immunosuppression, thymic atrophy, hepatotoxicity, tumor promotion, and disturbances of steroid hormone action. Since PCBs are present in environmental and tissue samples as complex mixtures, we investigated the possible interaction of non-ortho coplanar congeners with other major PCBs, which are less active or inactive as dioxin receptor agonists. As a parameter for dioxin receptor activation, induction of CYP1A-catalyzed 7-ethoxyresorufin O-deethylase (EROD) was determined in rat hepatocytes in primary culture and in the rat hepatoma cell line H4IIE. In rat hepatocytes, individual EC50-values and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalency factors (TEFs) for the non-ortho and mono-ortho coplanar PCBs 126, 169, 105, 118 and 156, were in good agreement with published data from in vivo experiments, while in H4IIE cells coincidence was lower. However, in both cell systems TEFs for PCB 77 were significantly higher than reported from experiments in rats. In an approximately equipotent mixture the six potent PCB congeners showed perfect additive behaviour in both cell systems. In contrast, addition of a tenfold surplus of abundant mono- and di-ortho PCBs (28, 52, 101, 138, 153 and 180) led to an almost threefold higher TEF than predicted. This finding suggests a moderate synergistic enhancement of the inducing potency of potent PCBs by less potent congeners, present in abundance in environmental and tissue samples.