Radiofrequency ablation as locoregional therapy for unresectable hepatic malignancies: initial results in 24 patients with 5-years follow-up

Radiofrequency ablation (RFA) is one treatment modality for unresectable liver metastases. Patients with hepatic malignancies (n = 24) underwent elective RFA. All tumors were ablated with a curative intent, with a margin of 1 cm, in a single session of RFA. The median diameter of tumor was 3.1 cm (range 1.7-6.9 cm). Studied patients were not candidates for resection due to multifocal hepatic disease, extrahepatic disease, proximity to major vascular structures or presence of cirrhosis with functional hepatic reserve inadequate to tolerate major hepatic resection. Complete tumor necrosis was achieved in 87.5% and tumor recurred in 3 patients (12.5%) with lesions larger than 5 cm. Distant intrahepatic recurrence was diagnosed in another 4 (16.7%). Distant metastases were found in 7 (29.2%) patients. Four of these 7 patients had also distant intrahepatic recurrence of disease. Two and 5-years survival rates were 41.7% (10 patients) and 8.3% (2 patients) respectively. RFA is safe and effective option for patients with unresectable hepatic malignancies smaller than 5 cm without distant metastatic disease. RF ablation resulted in complete tumor necrosis in 87.5% with 2 and 5-years survival rates much higher than with chemotherapy alone or only supportive therapy, when survival is measured in weeks or months. If RFA is unavailable, percutaneous ethanol injection therapy can be done but with inferior survival rates.     

Fucosylation enhances colonization of ticks by Anaplasma phagocytophilum

Fucosylated structures participate in a wide range of pathological processes in eukaryotes and prokaryotes. The impact of fucose on microbial pathogenesis, however, has been less appreciated in arthropods of medical relevance. Thus, we used the tick‐borne bacterium Anaplasma phagocytophilum– the agent of human granulocytic anaplasmosis to understand these processes. Here we show that A. phagocytophilum uses α1,3‐fucose to colonize ticks. We demonstrate that A. phagocytophilum modulates the expression of α1,3‐fucosyltransferases and gene silencing significantly reduces colonization of tick cells. Acquisition but not transmission of A. phagocytophilum was affected when α1,3‐fucosyltransferases were silenced during tick feeding. Our results uncover a novel mechanism of pathogen colonization in arthropods. Decoding mechanisms of pathogen invasion in ticks might expedite the development of new strategies to interfere with the life cycle of A. phagocytophilum.     

Carbonate facies evolution from the late albian to Middle Cenomanian in Southern Istria (Croatia): influence of synsedimentary tectonics and extensive organic carbonate production

Summary During the Late Albian, Early and Middle Cenomanian in the NW part of the Adriatic Carbonate Platform (presentday Istria) specific depositional systems characterised by frequent lateral and vertical facies variations were established within a formerly homogeneous area, ranging from peritidal and barrier bars to the offshore-transition zone. In southern Istria this period is represented by the following succession: thin-bedded peritidal peloidal and stromatolitic limestones (Upper Albian); well-bedded foreshore to shoreface packstones/grainstones with synsedimentary dliding and slumping (Vraconian-lowermost Cenomanian); shoreface to off-shore storm-generated limestones (Lower Cenomanian); massive off-shore to shoreface carbonate sand bodies (Lower Cenomanian); prograding rudist bioclastic subaqueous dunes (Lower to Middle Cenomanian); rudist biostromes (Lower to Middle Cenomanian), and high-energy rudist and ostreid coquina beds within skeletal wackestones/packstones (Middle Cenomanian). Rapid changes of depositional systems near the Albian/Cenomanian transition in Istria are mainly the result of synsedimentary tectonics and the establishment of extensive rudist colonies producing enormous quantities of bioclastic material rather than the influence of eustatic changes. Tectonism is evidenced by the occurrence of sliding scars, slumps, small-scale synsedimentary faults and conspicuous bathymetric changes in formerly corresponding environments. Consequently, during the Early Cenomanian in the region of southern Istria, a deepening of the sedimentary environments occurred towards the SE, resulting in the establishment of a carbonate ramp system. Deeper parts of the ramp were below fair-weather wave base (FWWB), while the shallower parts were characterised by high-energy environments with extensive rudist colonies, and high organic production leading to the progradation of bioclastic subaqueous dunes. This resulted in numerous shallowing- and coarsening-upwards clinostratified sequences completely infilling formerly deeper environments, and the final re-establishment of the shallow-water environments over the entire area during the Middle Cenomanian.     

The Drosophila Neurally Altered Carbohydrate Mutant Has a Defective Golgi GDP-fucose Transporter

Studying genetic disorders in model organisms can provide insights into heritable human diseases. The Drosophila neurally altered carbohydrate (nac) mutant is deficient for neural expression of the HRP epitope, which consists of N-glycans with core α1,3-linked fucose residues. Here, we show that a conserved serine residue in the Golgi GDP-fucose transporter (GFR) is substituted by leucine in nac(1) flies, which abolishes GDP-fucose transport in vivo and in vitro. This loss of function is due to a biochemical defect, not to destabilization or mistargeting of the mutant GFR protein. Mass spectrometry and HPLC analysis showed that nac(1) mutants lack not only core α1,3-linked, but also core α1,6-linked fucose residues on their N-glycans. Thus, the nac(1) Gfr mutation produces a previously unrecognized general defect in N-glycan core fucosylation. Transgenic expression of a wild-type Gfr gene restored the HRP epitope in neural tissues, directly demonstrating that the Gfr mutation is solely responsible for the neural HRP epitope deficiency in the nac(1) mutant. These results validate the Drosophila nac(1) mutant as a model for the human congenital disorder of glycosylation, CDG-IIc (also known as LAD-II), which is also the result of a GFR deficiency.     

Intact radial and median nerve after open third degree distal fracture of the humerus

A 54 year old man sustained a third degree open fracture at the distal part of the right humerus with massive soft tissue defect involving most of the upper arm. The radial and median nerves were completely bared and exposed by 6 cm for radial and 3 cm for median nerve. The nerves were in continuity, but there was complete rupture of surrounding muscles: biceps, triceps and brachialis. The fracture was stabilized by external fixation method--reinforced by wires. Preoperative and postoperative sensorimotor status of the right hand was good. One year later sensory and motoric status of right hand showed no deficiencies, but flexion and extension in elbow were limited to 100 and 180 degrees respectively. Pronosupination was restricted. This case report is consistent with results of biomechanical studies in vitro confirming high tolerance of radial and median nerve to stretching injury.     

Modulation of neural carbohydrate epitope expression in Drosophila melanogaster cells

Neural pathways in invertebrates are often tracked using anti-horseradish peroxidase, a cross-reaction due to the presence of core alpha1,3-fucosylated N-glycans. In order to investigate the molecular basis of this epitope in a cellular context, we compared two Drosophila melanogaster cell lines: the S2 and the neuronal-like BG2-c6 cell lines. As shown by mass spectrometric and chromatographic analyses, only the BG2-c6 cell line expresses alpha1,3/alpha1,6-difucosylated N-glycans, a result that correlates with anti-horseradish peroxidase binding. Of all four alpha1,3-fucosyltransferase homologues previously identified, the core alpha1,3-fucosyltransferase (FucTA; EC 2.4.1.214) is expressed in the neuronal cell line as well as throughout fly development and in heads and bodies of flies of both sexes. This pattern is distinctive in comparison with the expression of the other three alpha1,3-fucosyltransferase homologues (FucTB, FucTC, and FucTD). Furthermore, only transfection of FucTA cDNA into S2 cells resulted in expression of the anti-horseradish peroxidase epitope, a result compatible with its substrate specificity in vitro. Finally, silencing of FucTA by RNAi in the neuronal cell line led to a significant reduction of anti-horseradish peroxidase binding. The present study, in conjunction with our previous in vitro data, thereby shows that FucTA is indispensable for expression of the neural carbohydrate epitope in Drosophila cells.     

Growth Conditions in In Vitro Culture Can Induce Oxidative Stress in <Emphasis Type="Italic">Mammillaria gracilis</Emphasis> Tissues

In vitro propagated plants of Mammillaria gracilis Pfeiff. (Cactaceae) develop calli without any exogenous growth regulators. This habituated tissue spontaneously regenerates morphologically normal as well as hyperhydric shoots. In this study, a possible involvement of activated oxygen metabolism in habituation and hyperhydricity in in vitro propagated plants of Mammillaria gracilis Pfeiff. (Cactaceae) was investigated. Significantly higher malondialdehyde (MDA) and carbonyl contents as well as hydrogen peroxide (H₂O₂) production were observed in habituated callus (HC), hyperhydric regenerated shoots (HS), and tumors (TT) in comparison to normal regenerated shoots (NS). Lipoxygenase (LOX) activity showed a similar trend, with a clear increase in activity in HC and HS. The activities of antioxidative enzymes, namely, peroxidase (POX), ascorbate peroxidase (APX), and catalase (CAT), were also higher in HC, HS, and TT, whereas an increase in superoxide dismutase (SOD) activity was observed in HC and HS. The majority of antioxidative isoenzymes were common to all cactus tissues, although a few tissue-specific bands were noticed. Significant decreases in phenylalanine ammonia lyase (PAL) activity, total phenolic content, and lignification were found in HS, HC, and TT in comparison to NS. Our results showed the appearance of a prominent oxidative stress in HC, HS, and TT as well as a strong induction of the antioxidant system indicating that activated oxygen metabolism could be involved in habituation and hyperhydricity and linked to the loss of tissue organization in M. gracilis. B. Balen and M. Tkalec contributed equally to this work.     

The sequence in appearance and disappearance of impressiones gyrorum cerebri and cerebelli

We investigated the sequence and the intensity in the appearance and the disappearance of the impressiones gyrorum cerebri and cerebelli, of juga cerebralia and cerebellaria and of juga cerebellaria interlobularia in the collection of 34 macerated and disarticulated skull bones from the newborn to 30 years of age (68 specimens/halves of skulls) and 19 skulls in the period from 30 to 80 years of age (38 specimens). Juga cerebralia on the squama of the temporal bone and cerebral lamina of the frontal bone appeared already in the course of the first year of life, much earlier than cited in the literature. The intensity of the development of juga cerebralia increased to the third decade. After that age, the intensity decreased gradually, and the juga cerebralia disappeared completely in parietal bones, in the cerebral fossae of the occipital bones and finally in most cases also on the cerebral lamina of the frontal bones. Juga cerebellaria and impressiones gyrorum cerebelli appeared in the middle of the second year of age and persisted to the ten years of age, which coincides with the closure of the fissures among the parts of the occipital bone. Jugum cerebellare intersemilunare appeared in the first year of life and persisted in its complete length, or interrupted in different sections of its course, during the whole life. The intensity in appearance of juga is partly influenced by the increasing thickness of the diploe.     

Wood dust exposure in wood industry and forestry

The aim of the study was to determine occupational exposure in Croatian wood processing industry and forest workers to harmful effects of wood dust on the risk of nose, nasal cavity and lung carcinoma. Mass concentrations of respirable particles and total wood dust were measured at two wood processing plants, three woodwork shops, and one lumbering site, where 225 total wood dust samples and 221 respirable particle samples were collected. Wood dust mass concentration was determined by the gravimetric method. Mass concentrations exceeding total wood dust maximal allowed concentration (MAC, 3 mg/m3) were measured for beechwood and oakwood dust in 38% (79/206) of study samples from wood processing facilities (plants and woodwork shops). Mass concentrations of respirable particles exceeding MAC (1 mg/m3) were recorded in 24% (48/202) of samples from wood processing facilities (mean 2.38 +/- 2.08 mg/m3 in plants and 3.6 +/- 2.22 mg/m3 in woodwork shops). Thus, 13% (27/206) of work sites in wood processing facilities failed to meet health criteria according to European guidelines. Launching of measures to reduce wood dust emission to the work area is recommended.     

Ovarian cancer: PCD and brain metastases

Paraneoplastic cerebellar degeneration (PCD), the one of the most common paraneoplastic syndromes, refer to clinical disorders associated mostly with lung, ovarian and breast cancer, but not directly caused by the cancer or its metastases. Pathologic finding is an extensive loss of Purkinje cells in the cerebellum. Immunohistochemically, the auto-antibodies on the Purkinje cells had been detected. Clinically, PCD is characterized by sub-acutely evolving pancerebellar symptoms. Neurological dysfunction may appear before the detection of the underlying cancer. Therefore, the surgical exploration is necessary for the final diagnosis. The patient undergoes specific therapy. Soon, neurological status of the patient gets irreparable worse. Death come usually 2-3 years after the first symptoms of the PCD occurs. Case of a 63-years old woman with PCD as the first evidence of her cancer is reported. The patient developed brain metastases and died almost 3 years after the first symptoms of PCD occur