Changes in the cerebellar cytoarchitecture of hibernating hedgehog Erinaceus europaeus L. (Mammalia): an immunocytochemical approach

Hibernation is an amazing animal strategy to survive when the environmental temperature is very low and food resources are scarce. Successful hibernation requires a variety of complex biological adaptations, in which the brain plays a central regulatory role. Currently, little information is available regarding the morphology and functional activity of specific neurons within the cerebellar cytoarchitecture of hibernating animals. In the present study, we investigated the immunohistochemical expression of essential proteins in the cerebellum of a mammalian hibernator (i.e. hedgehog Erinaceus europaeus L.), focusing on (i) Purkinje neurons, the sole output cells of the cerebellar cortex; (ii) selected neurotransmitters involved in hibernation processes; (iii) intracellular calcium homeostasis, considering that calcium is also an important regulator of neurotransmission mechanisms; and (iv) cytoskeletal proteins, involved in maintenance of neuronal shape and axon calibre. Specifically, we studied in situ immunocytochemical changes during the torpor state of hibernation (November–March) versus the activity phase (April–September). We employed different selected markers, i.e. glutamic acid decarboxylase (GAD67) and postsynaptic glutamate ionotropic receptor GluR2-3, different calcium-binding proteins (i.e. calbindin, parvalbumin and calretinin) and cytoskeletal components (i.e. pNF-H and MAP2). In summary, our data in hibernating animals demonstrated: (i) downregulation of GAD67, indicating loss/changes of synaptic contacts on Purkinje somata and dendrites; (ii) GluR2-3 upregulation in Purkinje neurons, with a drastic decrease of calbindin expression; and (iii) decrease of normal mechanisms regulating intracellular calcium homeostasis. We also found a decrease/modification in the distribution of cytoskeletal proteins, particularly evident for pNF-H. Changes in the functional activity of Purkinje cells were accompanied by some morphological dendrite alterations, signs of degeneration in cell somata and flattened basket pinceaux at the Purkinje axon hillock. These findings confirm that hibernation makes heterothermic animals a valuable model to study physiological adaptations to adverse conditions, and also for understanding cellular and molecular mechanisms aimed at preserving mammalian organs from full degeneration and death

Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme

Biliary complications often lead to acute and chronic liver injury after orthotopic liver transplantation (OLT). Bile composition and secretion depend on the integrated action of all the components of the biliary tree, starting from hepatocytes. Fatty livers are often discarded as grafts for OLT, since they are extremely vulnerable to conventional cold storage (CS). However, the insufficiency of donors has stimulated research to improve the usage of such marginal organs as well as grafts. Our group has recently developed a machine perfusion system at subnormothermic temperature (20°C; MP20) that allows a marked improvement in preservation of fatty and even of normal rat livers as compared with CS. We sought to evaluate the response of the biliary tree of fatty liver to MP20, and a suitable marker was essential to this purpose. Alkaline phosphatase (AlkP, EC 3.1.3.1), frequently used as marker of membrane transport in hepatocytes and bile ducts, was our first choice. Since no histochemical data were available on AlkP distribution and activity in fatty liver, we have first settled to investigate AlkP activity in the steatotic liver of fatty Zucker rats (fa/fa), using as controls lean Zucker (fa/+) and normal Wistar rats. The AlkP reaction in Wistar rats was in accordance with the existing data and, in particular, was present in bile canaliculi of hepatocytes in the periportal region and midzone, in the canals of Hering and in small bile ducts but not in large bile ducts. In lean ZR liver the AlkP reaction in Hering canals and small bile ducts was similar to Wistar rat liver but hepatocytes had lower canalicular activity and besides presented moderate basolateral reaction. The difference between lean Zucker and Wistar rats, both phenotypically normal animals, could be related to the fact that lean Zucker rats are genotypically heterozygous for a recessive mutated allele. In fatty liver, the activity in ductules and small bile ducts was unchanged, but most hepatocytes were devoid of AlkP activity with the exception of clusters of macrosteatotic hepatocytes in the mid-zone, where the reaction was intense in basolateral domains and in distorted canaliculi, a typical pattern of cholestasis. The interpretation of these data was hindered by the fact that the physiological role of AlkP is still under debate. In the present study, the various functions proposed for the role of the enzyme in bile canaliculi and in cholangiocytes are reviewed. Independently of the AlkP role, our data suggest that AlkP does not seem to be a reliable marker to study the initial step of bile production during OLT of fatty livers, but may still be used to investigate the behaviour of bile ductules and small bile ducts

Cancer: New needs, new models. is it time for a community oncologist? another brick in the wall

Over the last few decades, thanks to early detection, effective drugs, and personalized treatments, the natural history of cancer has radically changed. Thanks to these advances, we have observed how survival of cancer patients has increased, becoming an ever more important goal in cancer care. Effective clinical governance of survivorship care is essential to ensure a successful transition between active and post-treatment life, identifying optimization of healthcare outcomes and quality of life for patients as the primary objectives. For these reasons, potential intervention models must consider these differences to rationalize the available resources, including economic aspects. In this perspective, analyzing the different models proposed in the literature to manage this type of patients, we focus on the possible role of the so-called “community oncologist”. As a trained health professional, also focused on longevity, he could represent the right management solution in all those “intermediate” clinical conditions that arise between the hospital specialist, frequently overworked, and the general practitioner, often biased by the lack of specific expertise

A phase II study of sequential chemotherapy with docetaxel after the weekly PELF regimen in advanced gastric cancer. A report from the Italian group for the study of digestive tract cancer

In advanced gastric cancer, we investigated feasibility and activity of sequential chemotherapy with docetaxel after an intensive weekly regimen consisting of cisplatin, epidoxorubicin, fluorouracil, leucovorin (PELF) plus filgrastim. Chemotherapy-naive patients with relapsed or metastatic gastric cancer received 8 weekly administrations of chemotherapy with cisplatin 40 mg/m2, fluorouracil 500 mg/m2,epi-doxorubicin 35 mg/m2, 6S-steroisomer of leucovorin 250 mg/m2and glutathione 1.5 g/m2. On the other days filgrastim 5 μg kg–1was administered by subcutanous injection. Subsequently, patients with partial response or stable disease received 3 cycles of docetaxel 100 mg/m2every 3 weeks. 40 patients have been enrolled and they are evaluable for response and toxicity. After the PELF regimen, 3 patients achieved complete response, 13 patients showed partial response, 21 patients had stable disease and 3 patients progressed (40% response rate; 95% CI 25% to 55%). After docetaxel, 9 out 34 patients improved the outcome (26.5%); 7 patients with stable disease achieved partial response and 2 patients with partial response achieved complete response. The overall response rate in the 40 patients was 57.5% (95% CI, 42.5% to 72.5%). The PELF regimen did not cause any grade IV toxicity, the most frequent grade III acute side-effects were thrombocytopenia and vomiting which occurred in the 10% of 320 PELF cycles. Docetaxel caused grade III–IV neutropenia and thrombocytopenia in the 10% and the 19% of cycles respectively. Fatigue was a frequent side-effect during both PELF and docetaxel chemotherapy. The sequential application of docetaxel after PELF chemotherapy gained major objective responses with manageable toxicity. This strategy is worth of further investigation in the setting of palliative or neoadjuvant chemotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.co

Exact Histogram Specification Optimized for Structural Similarity

An exact histogram specification (EHS) method modifies its input image to have a specified histogram. Applications of EHS include image (contrast) enhancement (e.g., by histogram equalization) and histogram watermarking. Performing EHS on an image, however, reduces its visual quality. Starting from the output of a generic EHS method, we maximize the structural similarity index (SSIM) between the original image (before EHS) and the result of EHS iteratively. Essential in this process is the computationally simple and accurate formula we derive for SSIM gradient. As it is based on gradient ascent, the proposed EHS always converges. Experimental results confirm that while obtaining the histogram exactly as specified, the proposed method invariably outperforms the existing methods in terms of visual quality of the result. The computational complexity of the proposed method is shown to be of the same order as that of the existing methods. Index terms: histogram modification, histogram equalization, optimization for perceptual visual quality, structural similarity gradient ascent, histogram watermarking, contrast enhancement

An analysis of the social and economic costs of breast cancer in Italy

Breast cancer is the most prevalent cancer affecting women and it represents an important economic burden. The aim of this study was to estimate the socio-economic burden of breast cancer (BC) in Italy both from the National Health Service (NHS) and the government perspectives (costs borne by the social security system)