FTY720 in combination with cyclosporine - an analysis of skin allograft survival and renal function

Acute and chronic nephrotoxicity caused by CsA Continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation.FTY720 is a new Compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens.In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney.Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose Could prevent graft rejection and avoid nephrotoxicity. (c) 2006 Elsevier B.V. All rights reserved.

Angiogenesis and skin carcinomas with skull base invasion: A case-control study

Background. Some skin carcinomas may be very aggressive. Intensity of angiogenesis, measured by intratumoral vessel density using expression of CD34, has been associated with tumor aggressiveness. In this study, the expression of CD34 in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) with skull base invasion was compared with that in tumors with good outcome.Methods. Expression of CD34 was graded as mild, moderate, and intense, in 24 BCCs and 11 SCCs with skull base invasion. The control group included 23 BCCs and 10 SCCs.Results. Intense expression of CD34 was noted in 25.00% of BCCs with skull base invasion, compared with 4.35% in the control group (p =.058). Regarding SCCs, intense expression of CD34 was found in 54.55% of aggressive tumors, compared with 10.00% in the control group (p = 133).Conclusions. A trend toward denser microvascular angiogenesis was observed in both BCCs and SCCs with skull base invasion compared with less aggressive controls. (C) 2004 Wiley Periodicals, Inc.

Water sorption enthalpy-entropy compensation based on isotherms of plum skin and pulp

The net isosteric heat and entropy of water sorption were calculated for plum, based on sorption isotherms obtained by the static gravimetric method at different temperatures (20 to 70 degrees C). The Guggenheim-Anderson-deBoer model was applied to the experimental data giving a good agreement between experimental and calculated values. The net isosteric heat of water sorption, estimated by applying Claussius-Clapeyron equation to sorption isotherms, was found to be different for plum skin and pulp, mainly at low moisture contents, and could be well adjusted by an empirical exponential relationship. Plots of enthalpy in contrast to entropy provided the isokinetic temperatures for skin and pulp, indicating an enthalpy-controlled sorption process. Thermodynamic data on water sorption for plums are not found in literature, as opposed to prunes for which the data are abundant.

Analysis of CDKN1A polymorphisms: markers of cancer susceptibility?

The CDKN1A (TP21)(2) gene encodes a 21-kD protein that is a critical downstream mediator of wild-type TP53 and an important regulator of the cell cycle. Failure in the function of this gene would be expected to result in abnormal cell proliferation and transformation. Tumor-associated mutations of the coding region of the TP21 are rare. on the other hand, some TP21 polymorphisms have been identified and characterized by single base substitutions. In the present study, we investigated the potential role of TP21 gene polymorphisms in skin, head, and neck tumorigenesis. A total of 261 samples were examined by polymerase chain reaction single-strand conformational analysis, and one mutation at codon 31 and four polymorphisms in exons 2 (codon 55) and 3 [nucleotide (nt)590] and in promoter region (nt2298) were identified. In conclusion, this investigation confirmed the rarity of mutations in this gene, arguing against a role for TP21 mutations in skin, head, and neck cancers. Also, our results show significant differences in nt2298 allele frequencies between normal individuals and skin malignant tumors (P < 0.05). The results suggest that this polymorphism affects TP21 transactivator binding and may be important during the pathogenesis of skin cancer. (C) 2003 Elsevier B.V. All rights reserved.

Immunolocalization of estrogen and progesterone receptors in neuroendocrine tumors of lung, skin, gastrointestinal and female genital tracts

Expression of estrogen (ER) and progesterone (PR) receptors has traditionally been associated with hormone-responsive organs, such as breast, ovary, and endometrium, and carcinomas arising therefrom. More recently, examples of ''unexpected'' ER or PR expression have been reported, particularly in tumors of endocrine tissues, such as thyroid and pancreatic islet cells. We tested the hypothesis that neuroendocrine tumors of various primary and metastatic sites might also express ER or PR or both by performing a retrospective immunohistochemical study in a series of 59 formalin- or mechacarn-fixed neuroendocrine carcinomas of various sites, including lung, skin, gastrointestinal and female genital tracts, and including carcinoid and atypical carcinoid tumors, small cell carcinomas, and Merkel cell carcinomas. We employed the anti-ER monoclonal antibody 1D5 and the anti-PR monoclonal antibody PgR1A6 using standard immunohistochemical techniques after microwave-based heat-induced epitope retrieval. Two of 28 carcinoid tumors demonstrated ER positivity; six of 30 cases were positive for progesterone receptor only. In addition, PR expression was found in one of two cases of atypical carcinoid, in five of 25 cases of small cell carcinoma, and in one of two cases of Merkel cell carcinoma. None of the atypical carcinoids, small cell carcinomas, or Merkel cell carcinomas were ER positive. In most cases, the fraction of tumor cell nuclei that were positive was <50%. These studies add the spectrum of neuroendocrine tumors that can express these hormone receptors. Similar to the pattern previously described in the subsets of meningiomas and islet cell tumors, PR but not ER is detectable in most cases. These results underscore the caution that should be exercised in determining tissue origin of metastatic carcinomas based only on detection of hormone receptors by immunohistochemistry.

Cytogenetic study of neoplastic and nonneoplastic cells of the skin

We describe the cytogenetic study of six neoplastic and eight nonneoplastic skin samples from sun-exposed body sites or sites close to tumors. The cytogenetic findings revealed that chromosome rearrangements are common in sun-exposed normal skin, similar to the situation in cutaneous tumors, and suggest that such karyotypic abnormalities might be indicative of the genetic instability caused by specific mutations and resulting from carcinogenic exposure of the tissue.

Skin hypersensitivity tests in buffaloes parasitized with Toxocara vitulorum.

Skin tests were done using larval extract and excretory-secretory (ES) antigens injected intradermally in the neck area of 30, 11- to 200-day-old buffalo calves and nine 27- to 100-day postparturition buffalo cows, the skin of the buffaloes infected with Toxocara vitulorum, mainly calves, demonstrated a hypersensitive response to antigens, especially to the larval extract antigens. Skin hypersensitivity responses were characterized by the presence of dermal nodules with progressive induration and an increase of up to four times the size of the original area at 30 min (immediate type) and at 72 h (delayed type) after injection, Histological preparations of skin reactions at 72 h showed a typical mononuclear cell infiltration, with eosinophils and perivascular cuffing in most of the animals, Fecal examination of 75 animals showed that 65 (86.7%) buffalo calves (9-115 days old) were parasitized with T. vitulorum. The peak of egg output from these animals occurred when they were approximately 45 days old.

Effect of oxytocin on transepithelial transport of water and Na+ in distinct ventral regions of frog skin (Rana catesbeiana)

Thoracic, abdominal, and pelvic fragments of ventral skin of Rana catesbeiana were analysed regarding the effect of oxytocin on: (1) transepithelial water transport; (2) short-circuit current, (3) skin conductance and electrical potential difference; (4) Na+ conductance, the electromotive force of the Nat transport mechanism, and shunt conductance; (5) short-circuit current responses to fast Na+ by K+ replacement in the outer compartment, and (6) epithelial microstructure. Unstimulated water and Na+ permeabilities were low along the ventral skin. Hydrosmotic and natriferic responses to oxytocin increased from thorax to pelvis, Unstimulated Na+ conductance was greater in pelvis than in abdomen, the other electrical parameters being essentially similar in both skin fragments. Contribution of shunt conductance to total skin conductance was higher in abdominal than in pelvic skin. Oxytocin-induced increases of total skin conductance, Na+ conductance, and shunt conductance in pelvis were significantly larger than in abdomen, An oscillatory behaviour of the short-circuit current was observed only in oxytocin-treated pelvic skins. Decrease of epithelial thickness and increase of mitochondria-rich cell number were observed from thorax to pelvis, Oxytocin-induced increases of interspaces were more conspicuous in pelvis and abdomen than in thorax.