LIPSS-based functional surfaces produced by multi-beam nanostructuring with 2601 beams and real-time thermal processes measurement.

A unique combination of the ultrashort high-energy pulsed laser system with exceptional beam quality and a novel Diffractive Optical Element (DOE) enables simultaneous production of 2601 spots organized in the square-shaped 1 × 1 mm matrix in less than 0.01 ms. By adjusting the laser and processing parameters each spot can contain Laser Induced Periodic Surface Structures (LIPSS, ripples), including high-spatial frequency LIPSS (HFSL) and low-spatial frequency LIPSS (LSFL). DOE placed before galvanometric scanner allows easy integration and stitching of the pattern over larger areas. In addition, the LIPSS formation was monitored for the first time using fast infrared radiometry for verification of real-time quality control possibilities. During the LIPSS fabrication, solidification plateaus were observed after each laser pulse, which enables process control by monitoring heat accumulation or plateau length using a new signal derivation approach. Analysis of solidification plateaus after each laser pulse enabled dynamic calibration of the measurement. Heat accumulation temperatures from 200 to 1000 °C were observed from measurement and compared to the theoretical model. The temperature measurements revealed interesting changes in the physics of the laser ablation process. Moreover, the highest throughput on the area of 40 × 40 mm reached 1910 cm2/min, which is the highest demonstrated throughput of LIPSS nanostructuring, to the best of our knowledge. Thus, showing great potential for the efficient production of LIPSS-based functional surfaces which can be used to improve surface mechanical, biological or optical properties.

Alteration of Notch signaling and functionality of adipose tissue derived mesenchymal stem cells in heart failure.

AIM: Circulating mesenchymal cells increase in heart failure (HF) patients and could be used therapeutically. Our aim was to investigate whether HF affects adipose tissue derived mesenchymal cell (adMSC) isolation, functional characteristics and Notch pathway. METHODS AND RESULTS: We compared 25 patients with different degrees of HF (11 NYHA classes I and II and 14 NYHA III and IV) with 10 age and gender matched controls. 100% adMSC cultures were obtained from controls, while only 72.7% and 35.7% from patients with mild or severe HF (p<0.0001). adMSC from HF patients showed higher markers of senescence (p16 positive cells: 14±2.3% in controls and 35.6±5.6% (p<0.05) and 69±14.7% (p<0.01) in mild or severe HF; γ-H2AX positive cells: 3.7±1.2%, 19.4±4.1% (p<0.05) and 23.7±3.4% (p<0.05) respectively), lower proliferation index (Ki67 positive cells: 21.5±4.9%, 13.2±2.8% and 13.7±3.2%, respectively), reduced pluripotency-associated genes (Oct4 positive cells: 86.7±4.9%, 55±12% (p<0.05) and 43.3±8.7% (p<0.05), respectively; NANOG positive cells: 89.8±3.7%, 39.6±14.4% (p<0.01) and 47±8.1%, respectively), and decreased differentiation markers (α-sarcomeric actin positive cells: 79.8±4.6%, 49±18.1% and 47±12.1% (p<0.05) and CD31-positive endothelial cells: 24.5±2.9%, 0.5±0.5% (p<0.001) and 2.3±2.3% (p<0.001), respectively). AdMSC from HF patients also showed reduced Notch transcriptional activity (lowered expression of Hey 1 and Hey 2 mRNAs). Stimulation with TNF-α of adMSC isolated from controls affected the transcription of several components of the Notch pathway (reduction of Notch 4 and Hes 1 mRNAs and increase of Notch 2 and Hey 1 mRNAs). CONCLUSIONS: In HF yield and functionality of adMSC are impaired and their Notch signaling is downregulated.

The effects of a multimodal training program on burnout syndrome in gynecologic oncology nurses and on the multidisciplinary psychosocial care of gynecologic cancer patients: an Italian experience.

OBJECTIVE: In cancer care, the burden of psycho-emotional elements involved on the patient-healthcare provider relationship cannot be ignored. The aim of this work is to have an impact on the level of burnout experienced by European Institute of Oncology (IEO) gynecologic oncology nurses (N = 14) and on quality of multidisciplinary team work. METHOD: We designed a 12 session multimodal training program consisting of a 1.5 hour theoretical lesson on a specific issue related to gynecologic cancer patient care, 20 minute projection of a short film, and 1.75 hours of role-playing exercises and experiential exchanges. The Link Burnout Questionnaire (Santinello, 2007) was administered before and after the completion of the intervention. We also monitored the number of patients referred to the Psycho-oncology Service as an indicator of the efficacy of the multidisciplinary approach. RESULTS: After the completion of the program, the general level of burnout significantly diminished (p = 0.02); in particular, a significant decrease was observed in the "personal inefficacy" subscale (p = 0.01). The number of patients referred to the Psycho-oncology Service increased by 50%. SIGNIFICANCE OF RESULTS: Nurses are in the first line of those seeing patients through the entire course of the disease. For this reason, they are at a particularly high risk of developing work-related distress. Structured training programs can be a valid answer to work-related distress, and feeling part of a multidisciplinary team helps in providing patients with better psychosocial care.

Stem cell senescence and regenerative paradigms.

The term "cellular senescence" denotes a cellular response to several stressors that results in irreversible growth arrest, alterations of the gene expression profile, epigenetic modifications, and an altered secretome, all of which eventually impair the reparative properties of primitive cells, adding a layer of complexity to the field of regenerative medicine. The purpose of this review is to illustrate how cellular senescence could affect tissue repair and to propose interventions that aim at interfering with it.

Concerns and hopes for stem cell therapy in cardiology: focus on endothelial progenitor cells.

The crucial role played by the endothelium in cardiovascular disorders has been repetitively recognised. Endothelium injury has been implicated in atherosclerosis, thrombosis, hypertension and other cardiovascular diseases. Recently, however, research has undertaken a new avenue. As mature endothelial cells posses limited regenerative capacities, the interest has been switched to the circulating endothelial progenitor cells (EPCs). Indeed, the scientific community has made progress in understanding the role of EPCs in the maintenance of endothelial integrity and function as well as post natal neovascularisation. It has been suggested that these cells are able to home in the site of heart injury / damage and that they might take part in angiogenesis, giving hope for new treatment opportunities. There is evidence that reduced availability of EPCs or impairment of their function is associated with more severe CV disease and to comorbid risk factors. Different current drug regimes are able to influence bone marrow production and release of EPCs and several growth factors are considered for possible useful new therapeutic approaches. Thus, many studies into the potential use of EPCs in the clinical setting have recently been conducted with conflicting results. The goal of this review article is to discuss current therapies to regenerate new vessels and therefore to enhance myocardial function. The article overviews the search strategy and the pathophysiological aspects behind this therapy, consider the target currently under investigation and set the stage for new ideas.

UVC radiation-induced effect on human primary thyroid cell proliferation and HLA-DR expression.

The aim of this study was to examine how UVC irradiation will affect normal human thyroid cell proliferation and HLA-DR expression. Primary human thyroid cells were exposed to UVC (254 nm wavelength) irradiation. In some experiments 0.5 mM buthionine sulfoximine (BSO) was added. Apoptosis was detected measuring annexin V, proteins involved in apoptotic process (p53, Bax, Bcl-2, caspase 3, and 9) by immunoblot analysis and HLA-DR expression by FACS. UVC induced a cell cycle arrest in G0/G1 phase in the first 24 h, accumulation of cells in the S phase 72 h after treatment, and an increase of apoptotic cells. BSO pretreatment showed an earlier appearance and a higher percentage of apoptosis. p53, caspase 3 and 9 were increased, while Bax and Bcl-2 were decreased. We also observed a transient significant increase in HLA-DR expression. UVC inhibited cell proliferation and induced apoptosis in normal human primary thyroid cells. An inhibitor of glutathione synthesis induced an earlier appearance and higher percentage of apoptosis suggesting that oxidative stress may play a role. Apoptotis involved components of the intrinsic mitochondrial pathway. A transient increase in HLA-DR expression after UVC irradiation could play a role in inducing AITD.

Apurinic apyrimidinic endonuclease/redox effector factor 1 immunoreactivity and grading in hepatocellular carcinoma risk of relapse after liver transplantation.

Apurinic apyrimidinic endonuclease (APE1)/redox effector factor 1 (Ref-1), which is a multifunction protein involved in both transcriptional regulation of gene expression during adaptive cellular responses to oxidative stress and in the base excision repair pathway of DNA lesions generated as a consequence of oxidant-induced base damage, contributes to the maintenance of genome stability. APE1/Ref-1 is normally localized in the nucleus; cytoplasmic localization observed in several tumors has been correlated with a poor prognosis. Hepatocellular carcinoma (HCC) grading is an essential tool to predict the risk of relapse and patient prognosis, particularly in patients undergoing liver transplantation (OLT). The aim of this study was to identify the role of APE1/Ref-1 in predicting a posttransplant HCC relapse. We studied 48 patients transplanted for HCC to define grading as well as nuclear and cytoplasmic APE1/Ref-1 expression within neoplastic versus nonneoplastic parenchyma. We defined a cutoff of 60% of cytoplasmic APE1/Ref-1 expression to identify positive cases. At a minimum of 1.5-year follow-up after transplantation, 32 patients are alive and 16 patients are deceased after HCC relapse. Among low-grade HCC (grades 1 and 2), 76% of cases are alive; only 34% showed cytoplasmic APE1/Ref-1 immunoreactivity. Among the high-grade cases (grades 3 and 4), 50% were alive with 64% showing cytoplasmic immunoreactivity. Nuclear reactivity was generally similar either in neoplastic or in cirrhotic livers, irrespective of the grade. These data seemed to support the hypothesis of a predictive role of APE1/Ref-1 for HCC risk of relapse, which together with tumor grade by analysis of a pretransplant needle biopsy should aid decision making for OLT.

Infection due to a novel mycobacterium, mimicking multidrug-resistant Mycobacterium tuberculosis.

The treatment of multidrug-resistant tuberculosis (TB) requires the use, for long periods, of drugs liable to cause significant side effects. In the case of misdiagnosis of multidrug-resistant TB, the patient is exposed to toxic substances without any benefit. In low-income countries, where the microbiological diagnosis of TB relies on microscopy only, the misdiagnosis of multidrug-resistant TB is very frequent in patients persistently smear-positive despite anti-TB treatment, with the possibility of an infection due to non-tuberculous mycobacteria (NTM) being neglected. The isolation of a mycobacterium from the sputum of a Somali patient apparently confirmed the previous diagnosis of cavitary pulmonary disease. Preliminary investigations led, at first, to the strain being identified as multidrug-resistant Mycobacterium tuberculosis, with findings fully in agreement with the patient's history, which was characterized by repeated interruptions of anti-TB treatment. Thorough phenotypic and genotypic analyses led subsequently to the recognition that the strain was a previously unreported non-tuberculous mycobacterium. The patient, who was unresponsive to the anti-TB treatment, dramatically improved once a drug combination active against NTM was used. A major objective of this article is to alert the medical community to the risk, present also in settings in which sophisticated diagnostic techniques are used, that a cavitary infection due to NTM, and consequently not responding to the anti-TB standard regimen, will be mistaken for multidrug-resistant TB.

eSlide suite: an open source software system for whole slide imaging.

This short report briefly describes the principles underlying the telepathology technique known as whole slide imaging, and the design and implementation of a system for acquisition and visualisation of digital slides. The developed system, including an acquisition module and a visualisation module, is available as an open source on the Internet, together with sample acquired slides.

Evaluation of prostate cancer staging in organ donors: intraoperative histology on periglandular soft tissues-a proposal.

An histopathologic screening method for prostate cancer assessment in organ donors is crucial because of the widening of the donor pool to older individuals. Evaluation of cancer grading with multiple biopsies is fundamental in the cases of abnormal prostate-specific antigen (PSA) values and suspect ultrasound findings. However, multiple biopsies may fail to represent the whole neoplasia, and grading may be difficult particularly because there may not be information about capsular penetration. Since October 2007, 20 prostate autopsy specimens were submitted to an histopathologic screening method of the entire prostate based on extemporary frozen section analysis (maximum 75 minutes) of shavings of samples of the lateral surfaces of the prostate gland: namely, approximately 5 samples or 7 in the case of a large gland. We produced 3-mm-thick step sections at three levels: the first was immediately taken at the cutting level, and then 30-microm sections were discarded. The following three levels of 5 microm intervals for 10 sections for each level were evaluated. There were 7 cases of undiagnosed prostate cancer, three of which were demonstrated on frozen sections with neoplastic foci of extraglandular infiltration within connective and adipose tissues outside the gland. No neoplasia was present in the other 13 cases. In all cases, the final diagnosis was confirmed by the extemporary analysis. Our goal was to confirm the optimal number of samples that were representative of the whole prostatic contour, to define time to diagnosis and to evaluate reproducibility of frozen-section histopathologic screening compared with paraffin sections. This novel approach should permit a more refined risk-benefit analysis.

Co-localization of tryptase and cathepsin-G in mast cells in cutaneous mastocytosis.

Mastocytosis is a heterogeneous disease characterized by an abnormal growth and/or accumulation of clonal mast cells (MC) in one or more organs. The most frequent site of organ involvement is the skin. The aim of this study was to investigate the immunoreactivity to tryptase and to cathepsin-G of MC from human cutaneous mastocytosis and to compare their number in normal skin and cutaneous mastocytosis. Immunohistochemistry and dual immunofluorescence using anti-tryptase and anti-capthepsin-G antibodies was performed on biopsy specimens from 20 cases diagnosed as cutaneous mastocytosis. Tryptase-positive MC was more numerous as compared to cathepsin-G positive MC. Dual immunofluorescence for tryptase and cathepsin-G demonstrated a colocalization of tryptase and cathepsin-G in skin MC secretory granules. Morphometric evaluation of MC number demostrated that the number of both tryptase- and cathepsin-G-positive MC was significantly higher in cutaneous mastocytosis as compared to normal skin and that in both conditions the number of tryptase-positive MC was significantly higher as compared to the number of cathepsin-G-positive MC. In conclusion, in this study, for the first time we have demonstrated the presence of MC with immunoreactivity to cathepsin-G in human cutaneous mastocytosis, as well as the co-localization of tryptase and cathepsin-G in MC secretory granules.

Early oral versus "traditional" postoperative feeding in gynecologic oncology patients undergoing intestinal resection: a randomized controlled trial.

BACKGROUND: A randomized controlled trial was performed to assess the outcome of early oral postoperative feeding (EOF) compared with traditional oral feeding (TOF) in gynecologic oncology patients undergoing laparotomy with associated intestinal resection. METHODS: Patients aged 18-75 years, undergoing elective laparotomy, and with preoperative diagnosis of gynecologic malignancy, were eligible. Exclusion criteria included infectious conditions, intestinal obstruction, severe malnutrition, American Society of Anesthesiologists (ASA) score > or =4, and postoperative stay in the intensive care unit lasting >24 h. Patients allocated to EOF received liquid diet in the first postoperative day and then regular diet. Patients received traditional feeding scheme until resolution of postoperative ileus to start liquid diet. The primary end-point of the trial was length of hospital stay. RESULTS: Between January 1st, 2007 and March 15th, 2008, 40 patients were randomized to receive either EOF or TOF. Hospital stay in patients who received EOF (n = 18) was 6.9 days versus 9.1 days in the TOF group (n = 22) (P = 0.022). Requirements for analgesic and antiemetic drugs, intensity of pain, intestinal function recovery, mean levels of postoperative satisfaction, postoperative complications, and quality-of-life scores did not differ between the two groups. CONCLUSION: Early resumption of oral intake is feasible and safe in gynecologic oncology patients undergoing intestinal resection as part of a planned surgical procedure. Moreover, significant reduction in length of hospital stay was demonstrated.

Angiogenesis and mast cells in human breast cancer sentinel lymph nodes with and without micrometastases.

AIMS: An increasing number of mast cells have been reported in angiogenesis associated with solid and haematopoietic tumours. Data concerning the number of mast cells in neoplastic lymph nodes and their relationship with microvessel density are controversial. The aim was to correlate the extent of angiogenesis with the number of mast cells reactive with tryptase in biopsy specimens of sentinel lymph nodes with and without micrometastases obtained from patients with breast cancer. METHODS AND RESULTS: Specimens from sentinel lymph nodes obtained from 80 patients (40 with and 40 without micrometastases) were investigated immunohistochemically by using anti-CD31 and anti-tryptase antibodies. Angiogenesis, measured as microvessel counts, increased in parallel with the number of tryptase-positive mast cells and their values were significantly higher in lymph nodes with micrometastases compared with those without. CONCLUSIONS: Tryptase-positive mast cells may contribute, at least in part, to angiogenesis occurring in sentinel lymph nodes with micrometastases from patients with breast cancer.

Bone marrow B-cell clonal expansion in type II mixed cryoglobulinaemia: association with nephritis.

OBJECTIVES: To investigate the relationship between the pattern of bone marrow (BM) B-cell expansion and the clinical features of mixed cryoglobulinaemia (MC) syndrome. METHODS: Fifty-five patients with type II MC syndrome were analysed. Their median age was 64 yrs (range 24-82), the median disease duration was 6 yrs (range 1-26) and the mean follow-up after BM analysis was 2.65 yrs (s.d. = 1.33). Peripheral neuropathy was present in 33 patients (60%), nephritis in 14 (25.4%), skin ulcers in 14 (25.4%) and lymphoma or atypical lymphoproliferative disorder (LPD) in 17/55 (30.9%). Anti-HCV antibodies were found in 43/55 patients (78.2%). BM B-cell expansion was evaluated by a semi-nested PCR amplification of the V-D-J region of the IgH genes. RESULTS: A clonal B-cell expansion in the BM was found in 33/55 (60%) patients, while a polyclonal pattern in 22/55 (40%). A BM pattern of clonal B-cell expansion increased the risk of nephritis of about 10 times [odds ratio (OR) = 10.11, CI95%1.52-67.31], if compared to a polyclonal pattern. In contrast, the risk of skin ulcers was decreased in BM clonal cases (OR = 0.09, CI95%0.02-0.49). Overt lymphomas did not emerge from patients with BM monoclonal expansion (without clinical or histopathological features of lymphoproliferation; or with LPD) in a short-term, consistent with the finding that monoclonality was associated with nephritis and not with an underlying, not recognized lymphoma. CONCLUSION: BM clonal B-cell expansion is associated with nephritis in MC syndrome. Particular B-cell clones may be preferentially expanded and may play a pathogenic role in MC nephritis.

Superiority of transplantation versus resection for the treatment of small hepatocellular carcinoma.

The best therapy for hepatocellular carcinoma (HCC) is still debated. Hepatic resection (HR) is the treatment of choice for single HCC in Child A patients, whereas liver transplantation (OLT) is usually reserved for Child B and C patients with multiple nodules. The aim of this study was to compare HR and OLT for HCC within the Milan criteria on an intention-to-treat basis. Forty-eight patients were treated by OLT and 38 by HR. Three- and 5-year patient survival rates were significantly higher (P = .0057) in the OLT group (79% and 74%) than after HR (61% and 26%). The 3- and 5-year disease-free survival rate was better (P = .0005) for OLT (74% and 74%) versus HR (41% and 11%). The probability of HCC recurrences after resection was greater (P = .0002) than after transplantation, achieving 31% and 76% for HR and 2% and 2% for OLT at 3 and 5 years after surgery. The median waiting list time was 118 days; two patients dropped out for HCC progression. We concluded that OLT is superior to HR for small HCC in cirrhotic patients assuming that OLT can be performed within 6 to 10 months after listing to reduce dropouts due to tumor progression.

Treatment of inclusion body myositis with cyclosporin-A or tacrolimus: successful long-term management in patients with earlier active disease and concomitant autoimmune features.

OBJECTIVE: Sporadic inclusion body myositis (s-IBM) is a chronic, progressive, inflammatory myopathy of unknown aetiology, generally resistant to immunosuppressive therapy. Given that lymphocyte infiltrates in s-IBM muscle tissue are CD8+ T cells, targeting these cells may represent a valid approach. PATIENTS AND METHODS: Three patients with biopsy-proven s-IBM, high creatine kinase levels at diagnosis, two of whom with associated immune disorders, were treated with either cyclosporin-A (CyA) or tacrolimus, in combination with high doses of corticosteroids (CS), followed by rapid CS tapering. Clinical assessment and laboratory evaluation were performed every three months for the first year and then every six months for the second year. RESULTS: Based on muscle strength assessment and muscle enzyme serum levels, a major clinical response was observed at month +3 in two out of the three patients. A complete clinical response and major clinical response were obtained at month +6, in two and one patient, respectively. Normalization of serum muscle enzymes was observed in all. Steroids could be tapered to very low doses in all patients and were suspended early in one. Laboratory, but not clinical relapse occurred in one patient and was controlled by increasing the CyA dose. Treatment was well tolerated, with no serious adverse events occurring. All three patients are maintaining immunosuppressive therapy. CONCLUSION: Calcineurin inhibitors may represent a useful option for the long-term management of s-IBM, possibly in a subset characterized by a short duration with high disease activity or associated autoimmune manifestations.

Satisfacción en pacientes con reconstrucción mamaria con colgajo D. I. E. P / Patient’s satisfaction after diep flap reconstruction

La reconstrucción mamaria tras mastectomía se realiza primordialmente para proporcionar calidad de vida a la paciente. Este estudio se desarrolló para valorar la satisfacción y calidad de vida de las pacientes reconstruidas mediante colgajo D.I.E.P. (Deep Inferior Epigastric Perforator)y evaluar el resultado estético de la reconstrucción. Treinta y tres pacientes, de 51 reconstrucciones mamarias con colgajo DIEP realizadas entre enero de 2000 y noviembre de 2004 fueron preguntadas acerca de aspectos generales relativos a la cirugía, imagen corporal y sensación subjetiva. El resultado de imagen corporal fue evaluado por dos observadores externos, un cirujano plástico y una enfermera, además de por la propia paciente. Para valorar la reconstrucción mamaria, se utilizó una escala de 4 puntos. La satisfacción general de nuestro estudio fue más elevada que la observada en estudios precedentes. Hemos conseguido una valoración alta en simetría, dentro de los parámetros objetivos y en integridad corporal entre los subjetivos. Hemos encontrado una correlación alta entre las respuestas de los observadores comparada con las respuestas de las propias pacientes. Por último, hemos visto una fuerte correlación entre integridad corporal y satisfacción general (AU)

Breast reconstructions after breast cancer surgery are primarily performed to improve patient’s quality of life. This study investigates patient’s satisfaction and quality of life with breast reconstruction after deep inferior epigastric perforator (D.I.E.P.) flap surgery and to evaluate the aesthetic result of the breast reconstruction. Thirty-three patiens, from fifty-one DIEP breast reconstruction made between January 2000 and December 2004 were answered about three questionnaires concerning to general aspect, body image, and subjective sensation. The body image outcome was also evaluated by one plastic surgeon and a nurse. The panel evaluated breast reconstruction on 4 subescales. General satisfaction in our study was higher than in previous ones. We have received a high degree of symmetry in the objetive evaluation and a high score in body integrity in the subjective evaluation. We have found a stronger correlation between clinical observer answers compared with patient´s assessment and a strong correlation between body integrity and general satisfaction outcome (AU)

Comparison of clinical and pathological staging and long-term results of liver transplantation for hepatocellular carcinoma in a single transplant center.

Liver transplantation (OLT) is a treatment for hepatocellular carcinoma (HCC) superimposed on cirrhosis provided that the disease meets defined criteria. The aim of the study was to evaluate our experience with respect to clinical and pathological staging and long-term results. From 1996 to 2005, 50 patients underwent OLT for HCC including 43 men (86%) and seven women (14%) of median age 57 years (range 37 to 67). All patients fulfilled the Milan criteria. The HCC diagnosis was based on preoperative imaging and alpha-fetoprotein levels; no tumor biopsy was performed. Upon histological examination of the resected specimens, we discovered 6 (12%) incidentalomas and 8 (16%) cases of no HCC. Finally we had 42 "true" HCC. Twenty-six patients (52%) have been downstaged and 10 (20%) upstaged by preoperative imaging; 15% were pT1, 45% were pT2, 27% pT3, and 13% pT4a. Twenty-six percent of cases exceeded the Milan criteria. One patient (pT4a) with microvascular invasion died of pulmonary metastases at 14 months after transplantation. No HCC recurrences within the liver have been encountered at a median follow-up of 20 months (range 0 to 80 months). Overall the estimated 1-, 3-, and 5-year survival rates were 83%, 77%, and 72%, respectively. One-, 3-, and 5-year estimated survival rates were 87%, 75%, and 75% for pT1, and pT2, and 75%, 67%, and 67% for pT3 and pT4a, respectively (P = .99). Based on our experience OLT for HCC has long-term results comparable to those without HCC despite the presence of a significant number of cases exceeding the Milan criteria upon pathological staging.

Do mast cells affect villous architecture? Facts and conjectures.

In adult life, the architecture of the intestinal villus is maintained by a complex series of epithelial-stromal interactions that involve different types of fixed and mobile cells located in the intestinal mucosa. Mast cells (MC) are normal constituents of the small bowel mucosa where they reside in the villous and pericryptal lamina propria as well as within the columnar epithelial cell layer. Besides being involved in numerous immune and inflammatory reactions in the context of both innate and acquired host defence, MC are known to exert important non-immunological functions like wound repair, extracellular matrix remodelling, angiogenesis and neurotrophism as well as modulation of fibroblast, epithelial cell and smooth muscle cell activity. These pleiotropic functions put MC in a central, strategic position to organize tissue defence, restore tissue damage and maintain tissue homeostasis. This review summarizes the most recent advances concerning the functional anatomy of the crypt-villus unit and discusses the way intestinal MC might become part of the instructive circuits that ultimately lead to the maintenance of a proper villous shape.

Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure.

In this study, we tested whether the human heart possesses a cardiac stem cell (CSC) pool that promotes regeneration after infarction. For this purpose, CSC growth and senescence were measured in 20 hearts with acute infarcts, 20 hearts with end-stage postinfarction cardiomyopathy, and 12 control hearts. CSC number increased markedly in acute and, to a lesser extent, in chronic infarcts. CSC growth correlated with the increase in telomerase-competent dividing CSCs from 1.5% in controls to 28% in acute infarcts and 14% in chronic infarcts. The CSC mitotic index increased 29-fold in acute and 14-fold in chronic infarcts. CSCs committed to the myocyte, smooth muscle, and endothelial cell lineages increased approximately 85-fold in acute infarcts and approximately 25-fold in chronic infarcts. However, p16(INK4a)-p53-positive senescent CSCs also increased and were 10%, 18%, and 40% in controls, acute infarcts, and chronic infarcts, respectively. Old CSCs had short telomeres and apoptosis involved 0.3%, 3.8%, and 9.6% of CSCs in controls, acute infarcts, and chronic infarcts, respectively. These variables reduced the number of functionally competent CSCs from approximately 26,000/cm3 of viable myocardium in acute to approximately 7,000/cm3 in chronic infarcts, respectively. In seven acute infarcts, foci of spontaneous myocardial regeneration that did not involve cell fusion were identified. In conclusion, the human heart possesses a CSC compartment, and CSC activation occurs in response to ischemic injury. The loss of functionally competent CSCs in chronic ischemic cardiomyopathy may underlie the progressive functional deterioration and the onset of terminal failure.