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Introduction Alveolar bone is critical in supporting natural teeth, dental implants as well as a removable and fixed prosthesis. Alveolar bone volume diminishes when its associated natural tooth is lost. Objective The aim of this study is to evaluate the effectiveness of bovine bone granules on alveolar bone socket augmentation for ridge preservation following atraumatic tooth extraction. Materials and methods Twenty medically fit patients (12 males and 8 females aged between 18 and 40 years) who needed noncomplicated tooth extraction of 1 mandibular premolar tooth were divided randomly and equally into 2 groups. In control group I, the empty extraction socket was left untreated and allowed to heal in a conventional way. In group II, the empty extraction socket wound was filled with lyophilized bovine bone xenograft granules 0.25 to 1 mm of size, 1 mL/vial. A resorbable pericardium membrane was placed to cover the defect. Clinical and 3-dimensional radiological assessments were performed at day 0, 3 months, and 9 months postoperative. Results There were no clinical differences in general wound healing between the groups. Comparisons within the groups showed a significant difference of bone resorption of 1.49 mm (95% confidence interval, 0.63-2.35) at 3 months, and further resorption of 1.84 mm (P ≤ 0.05) at 9 months in the control group. No significant changes of bone resorption were observed in group II during the same time interval. Comparison between groups showed a significant difference of bone resorption at 3 and 9 months (2.40 and 2.88 mm, respectively). Conclusion The use of lyophilized demineralized bovine bone granules in socket preservation to fill in the extraction socket seems essential in preserving the alveolar bone dimension as it showed excellent soft and hard tissue healing. This study concludes that the alveolar bone socket exhibited a dynamic process of resorption from the first day of tooth extraction. Evidence shows the possibility of using bovine bone granules routinely in socket volume preservation techniques following tooth extraction.

Cancer stem cells (CSCs) niche in the tumor microenvironment is responsible for cancer recurrence and therapy failure. To better understand its molecular and biological involvement in hepatocellular carcinoma (HCC) progression, one can design more effective therapies and tailored then to individual patients. While sorafenib is currently the only approved drug for first-line treatment of advanced stage HCC, its role in modulating the CSC niche is estimated to be small. By contrast, transforming growth factor (TGF)-β pathway seems to influence the CSC and thus may impact hallmarks of HCC, such as liver fibrosis, cirrhosis, and tumor progression. Therefore, blocking this pathway may offer an appealing and druggable target. In our study, we have used galunisertib (LY2157299), a selective ATP-mimetic inhibitor of TGF-β receptor I (TGFβI/ALK5) activation, currently under clinical investigation in HCC patients. Because the drug resistance is mainly mediated by CSCs, we tested the effects of galunisertib on stemness phenotype in HCC cells to determine whether TGF-β signaling modulates CSC niche and drug resistance. Galunisertib modulated the expression of stemness-related genes only in the invasive (HLE and HLF) HCC cells inducing a decreased expression of CD44 and THY1. Furthermore, galunisertib also reduced the stemness-related functions of invasive HCC cells decreasing the formation of colonies, liver spheroids and invasive growth ability. Interestingly, CD44 loss of function mimicked the galunisertib effects on HCC stemness-related functions. Galunisertib treatment also reduced the expression of stemness-related genes in ex vivo human HCC specimens. Our observations are the first evidence that galunisertib effectiveness overcomes stemness-derived aggressiveness via decreased expression CD44 and THY1.

The energy loss for swift heavy ions, covering Z=3-29(~0.2 - 5.0MeV/n), has been calculated in the elemental absorbers like C, Al and Ti. The present calculations are based on Bohr’s approach applicable in both classical and quantum mechanical regimes. The major input parameter, the effective charge, has been calculated in a different way without any empirical/semi-empirical parameterization. The calculated energy loss values have been compared with the available experimental data which results in a close agreement.

Aims The aim was to investigate relationships of Vitamin D receptor gene (VDR) polymorphisms to the components of MetS among Arabs adult residing in the United Arab Emirates. Methods A cross-sectional study of 198 Arabs adult (50 males and 148 females). Serum levels of glucose, vitamin D, HDL-C, and TG, and blood pressure were measured. FokI, BsmI & TaqI genotyping of VDR were investigated using PCR-RFLP technique. Results Age of the participants was 21(9) years with a BMI of 26.8(7.8) kg/m 2 . About 15% had MetS with serum vitamin D levels of 25.5(18.2) nmol/L. VDR genotyping yielded: FokI: 57.1% FF and 38.9% Ff, BsmI: 29.8% bb and 51.5% Bb, while TaqI showed 39.4% TT and 43.4% Tt. The ff carriers had higher total cholesterol [174(12.4) mg/dl] than FF and Ff genotypes. Bb carriers showed higher BMI and LDL-C than BB and bb genotypes. In females, FokI VDR polymorphism showed significant association with systolic blood pressure (SBP) and F allele carriers were at higher risk of developing high SBP [ x 2 = 4.4, df1, OR = 0.29 (95%CI: 0.087–0.98), p = 0.035]. Conclusion VDR gene polymorphisms were not associated with MetS, yet it may affect the severity of some of components of MetS, namely the association of BsmI with obesity, FokI and BsmI with dyslipidemia and FokI with SBP.

Highlights • miR-34a was decreased in both glioma and glioma stem cell-lines as compared to normal brain tissues. • Glioma stem cell-lines HNGC-2 and NSG-K16 possess the mesenchymal glioblastoma phenotype. • miR-34a over-expression in these cell lines decreased their proliferative and migratory potential, and induced apoptosis. • Rictor, a part of the mTORC2 complex, is a novel target for miR-34a in glioma stem cells. • The tumor suppressive function of miR-34a is mediated via Rictor and affects the AKT/mTOR pathway and Wnt signaling., MiRNA-34a is considered as a potential prognostic marker for glioma, as studies suggest that its expression negatively correlates with patient survival in grade III and IV glial tumors. Here, we show that expression of miR-34a was decreased in a graded manner in glioma and glioma stem cell-lines as compared to normal brain tissues. Ectopic expression of miR-34a in glioma stem cell-lines HNGC-2 and NSG-K16 decreased the proliferative and migratory potential of these cells, induced cell cycle arrest and caused apoptosis. Notably, the miR-34a glioma cells formed significantly smaller xenografts in immuno-deficient mice as compared with control glioma stem cell-lines. Here, using a bioinformatics approach and various biological assays, we identify Rictor, as a novel target for miR-34a in glioma stem cells. Rictor, a defining component of mTORC2 complex, is involved in cell survival signaling. mTORC2 lays downstream of Akt, and thus is a direct activator of Akt. Our earlier studies have elaborated on role of Rictor in glioma invasion (Das et al., 2011). Here, we demonstrate that miR34a over-expression in glioma stem cells profoundly decreased levels of p-AKT (Ser473), increased GSK-3β levels and targeted for degradation β-catenin, an important mediator of Wnt signaling pathway. This led to diminished levels of the Wnt effectors cyclin D1 and c-myc. Collectively, we show that the tumor suppressive function of miR-34a in glioblastoma is mediated via Rictor, which through its effects on AKT/mTOR pathway and Wnt signaling causes pronounced effects on glioma malignancy.

As part of its potential pro-tumorigenic actions, Transforming Growth Factor-(TGF)-β induces epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells. Whether EMT induces changes in tumor cell plasticity has not been fully explored yet. Here, we analyze the effects of TGF-β on the EMT and stem-related properties of HCC cells and the potential correlation among those processes. The translational aim of the study was to propose a TGF-β/EMT/stem gene signature that would help in recognizing HCC patients as good candidates for anti-TGF-β therapy. Results indicate that when TGF-β induces EMT in HCC cells, a switch in the expression of stem genes is observed and their stemness potential and migratory/invasive capacity are enhanced. However, TGF-β may induce a partial EMT in some epithelial HCC cells, increasing the expression of mesenchymal genes and CD44, but maintaining epithelial gene expression. Epithelial cells show higher stemness potential than the mesenchymal ones, but respond to TGF-β increasing their migratory and invasive capacity. In HCC patient samples, TGFB1 expression most frequently correlates with a partial EMT, increase in mesenchymal genes and CD44 expression, as well as maintenance or over-expression of epithelial-related genes.

Background. MicroRNAs (miRNAs) are increasingly being recognized as being involved in cancer development and progression in gliomas. Methods. Using a model cell system developed in our lab to study glioma progression comprising human neuroglial culture (HNGC)–1 and HNGC-2 cells, we report here that miR-145 is one of the miRNAs significantly downregulated during malignant transformation in glioblastoma multiforme (GBM). In a study using tumor samples derived from various glioma grades, we show that expression of miR-145 is decreased in a graded manner, with GBM patients showing lowest expression relative to lower-grade gliomas (P , .05) and normal brain tissues (P , .0001). Functional studies involving ectopic expression of miR-145 in glioma cells had a negative impact on cell proliferation and tumor development, as well as invasion and induced apoptosis, providing further support to the concept that inactivation of miR-145 is important for glioma disease pathogenesis. More notably, these growth-suppressive effects of miR-145 are mediated through its target proteins Sox9 and the cell adhesionassociated molecule adducin 3 (ADD3). Results. Inhibiting Sox9 and ADD3 rescued effects of miR-145 loss. Interestingly, miR-145 loss in glioma cells led to overexpression of molecules involved in cell proliferation, like cyclin D1, c-myc, and N-myc, as well as enhanced expression of cell adhesion- and invasion-related molecules N-cadherin and E-cadherin, an effect which was again restored upon miR-145 overexpression in glioma cells. The miR-145 promoter was methylated at its cytosine–phosphate–guanine (CpG) islands in the glioma cell lines studied. Conclusion. Our study demonstrates that miR-145 has a tumor-suppressive function in glioblastoma in that it reduces proliferation, adhesion, and invasion of glioblastoma cells, apparently by suppressing the activity of oncogenic proteins Sox9 and ADD3. Reduced levels of miR-145 may lead to neoplastic transformation and malignant progression in glioma due to unregulated activity of these proteins.

Background: The aim of this study was to evaluate the stability of immediate implant placement for alveolar bone augmentation and preservation with bovine bone graft following atraumatic tooth extraction. Materials and Methods: This was a prospective interventional study with convenient sampling (n = 10). Thirty patients aged between 18 and 40 years, who needed noncomplicated tooth extraction of mandibular premolar tooth, were sequentially divided equally into three groups. In Group I, simple extraction was done and the empty extraction socket left to heal conventionally. In Group II, extraction sockets were filled with lyophilized bovine granules only. In Group III, immediate implants were placed into extraction sockets, and the buccal gap was also filled with bovine granules. All groups were subjected to cone beam computed tomography scan for radiological evaluation. Assessment of biomechanical stability (radiofrequency analysis [RFA] was performed at 9 months postoperative for Group III to assess the degree of secondary stability of the implants using Osstell. Repeated measure analysis of variance (ANOVA) test was applied when comparing within each group at three different time intervals, whereas one‑way ANOVA was applied followed by post hoc‑tukey test when comparing between groups. P < 0.05 was considered statistically significant. Results: Radiological assessment reveals a significant difference of bone resorption in alveolar dimension within Group I; 1.49 mm (P = 0.002), and 0.82 mm (P = 0.005), respectively, between day 0 and 3 months. Comparison between Group I and III showed a highly significant difference of bone resorption in ridge width at 3 months 2.56 mm (P = 0.001) and at 9 months interval 3.2 mm (P < 0.001). High RFA values demonstrating an excellent biomechanical stability were observed in Group III at 9 months postoperatively. Conclusion: The insertion of immediate implants in extraction sockets with bovine bone augmentation of the buccal gap was able to preserve a greater amount of alveolar ridge volume. Key Words: Cone beam computed tomography, Immediate Dental Implant Loading, ridge, preservation

The goal of personalised therapy based on hepatocellular carcinoma (HCC) molecular characteristics is still beyond our grasp. Systemic treatments show poor efficacy, mainly because of the great heterogeneity of the tumour. Indeed, differences in aetiology, disease stage and biochemical composition of the fibrotic liver make cirrhosis itself a highly dyshomogeneous disease. Cancer cells grow in a cirrhotic microenvironment, interacting with stromal cells and engaging matrix components that differ from patient to patient, hampering the development of drugs to treat all patients. Growing evidence suggests a role for the cross-talk between HCC and the host stroma in driving disease progression and hence prognosis and survival. Many efforts have been devoted to identifying genes responsible for good or bad prognosis, but no study has yet proven helpful in guiding therapeutic choices and management over time, also taking into account the development of drug resistance. The questions of what to target and in which patient are still unsolved. In the personalised therapy scenario, the patient rather than the disease becomes the target of the therapy. However, this still requires an evidence-based medical approach. Herein, we will discuss how individual differences in terms of quality and quantity of the tissue microenvironment components affect progression of HCC. Then, we will highlight potential druggable pathways, also considering ongoing clinical trials. The development of biomarkers will be discussed in the light of new experimental research conducted with the aim of moving towards personalised therapy in patients with HCC.

Antecedentes e hipotesis La senalizacion del factor de crecimiento transformante-beta (TGF-β) en varios canceres humanos es un importante regulador de la transicion epitelio-mesenquimal (EMT) y puede guiar a las celulas a una de-diferenciacion de forma autocrina. Sin embargo, los mecanismos moleculares que integran el fenotipo mesenquimal con la adquisicion de propiedades de celula troncal tumoral (CSC) (tambien definida como celula iniciadora de tumores, TIC) todavia requieren una mayor investigacion. En el carcinoma hepatocelular (HCC), aun se sabe muy poco acerca de si el TGF-β regula la plasticidad celular y si eso podria estar relacionado con el proceso de EMT inducido por este factor. La hipotesis de este trabajo de tesis doctoral es que el TGF-β, que esta sobre-expresado en muchos tumores humanos de HCC, podria jugar un papel en la regulacion de EMT completa o parcial, lo que tambien podria modular la capacidad de stemness de las celulas. Objetivos El objetivo principal de este proyecto es analizar los efectos inducidos por el TGF-β sobre el fenotipo CSC y la interaccion con el programa de EMT en el carcinoma hepatocelular humano. Este objetivo se divide en cuatro objetivos mas especificos: 1. Analizar la relevancia de la via del TGF-β autocrino en la expresion de los genes de la EMT y CSC en diferentes celulas de HCC. 2. Investigar el efecto del silenciamiento de la expresion del Receptor I del TGF-β sobre el fenotipo EMT y las propiedades CSC. 3. Estudiar el efecto del tratamiento a largo plazo con el TGF-β en el fenotipo EMT y las propiedades stemness de celulas epiteliales de HCC. 4. Explorar las correlaciones in vivo entre los genes de TGF-β, stemness y EMT. Analisis de: I) los tumores de ratones con carcinogenesis hepatica inducida por la dietil-nitrosamina (DEN); II) tejidos humanos de HCC. Resultados/Conclusiones • La sobre-activacion de la via de TGF-β se correlaciona con un fenotipo mesenquimal, con mayores capacidades migratorias e invasivas y con la expresion de los marcadores CD90 y CD44. • En celulas con fenotipo plenamente mesenquimal, el TGF-β es critico no solo para la expresion de CD44 y las capacidades migratorias e invasivas, sino tambien para el control de las funciones relacionadas con stemness. • CD44 juega un papel crucial en la determinacion no solo del fenotipo mesenquimal y las habilidades tumorigenicas relacionadas con stemness, sino tambien en el potencial migratorio e invasivo de las celulas mesenquimales. • La estimulacion cronica de la via de TGF-β en las celulas Hep3B se correlaciona con un cambio en la expresion de genes epiteliales (EPCAM, CD133) por marcadores mesenquimales (CD44) relacionados con stemness, que confieren una ventaja tanto en el mantenimiento de las propiedades stemness como en una mejor capacidad para migrar e invadir. • En contraste con lo observado en las celulas Hep3B, la sobre-activacion de la via del TGF-β en celulas PLC/PRF/5 induce la expresion simultanea de EPCAM, CD133 y CD44, asi como un aumento en migracion e invasion. • Ademas, las celulas TβT-PLCCD44+ expresan genes epiteliales y mesenquimales, que muestran propiedades stemness similares a la mas epiteliales TβT-PLCCD44- pero una mucho mas alta capacidad migratoria e invasiva. • La hepatocarcinogenesis inducida por DEN en ratones coincide con aumento de TGF-β, una mezcla de genotipo epitelial/mesenquimal y la expresion simultanea de genes epiteliales y mesenquimales relacionados con stemness. • En tejidos tumorales de pacientes de HCC, la expresion de TGF-β se relaciona tanto con el fenotipo EMT (con la expresion predominante de genes mesenquimales), como con EMT parcial (con presencia simultanea de genes epiteliales y mesenquimales). Sin embargo, la firma genetica EMT/stemness mas frecuente coincide con la sobre regulacion de la expresion de TGF-β y con EMT parcial, lo que lleva a una expresion concomitante de genes epiteliales y mesenquimales relacionados con stemness.

The relationship between the standard passive mouse protection test or serum antibody titres measured by indirect haemagglutination or enzyme-linked immunosorbent assays and active protection in buffaloes immunized with different types of haemorrhagic septicaemia bacterins was investigated. Groups of 2–3 buffaloes were immunized with the bacterius currently in use in Asia, viz., broth bacterin (BB), alum precipitated vaccine (APV) and oil adjuvant vaccine (OAV) either subcutaneously (BB, APV) or intramuscularly (OAV) and challenged subcutaneously with virulent organisms at different periods post-immunization. Although the passive mouse protection and indirect haemagglutination tests carried out with the pre-challenge sera from vaccinated buffaloes revealed no relationship with active protection in buffaloes, a relationship was observed between the ELISA antibody titres and protection. In contrast, a dose-response relationship was observed between the homologous active and passive mouse protection test.

Two of the three buffaloes immunized with a non-adjuvanted broth bacterin were found to be protected against experimental challenge at 6 weeks but not at 3 months post-challenge. Similarly all buffaloes (4/4) immunized with alum-precipitated vaccine were protected at 6 months but only 1 of the 2 vaccinated animals were protected at 12 months post-immunization. On the other hand, buffaloes immunized with an oil adjuvant and a double emulsion vaccine were completely protected at 12 months post-immunization. Statistically significant differences between immunized versus non-immune animals became evident at 3 months post-immunization, although analysis of cumulative antibody titres of pre-challenge sera of vaccinated buffaloes surviving versus those succumbing to experimental challenge revealed significant by higher antibody titres in the former as compared to the latter group. These results suggested that there was a relationship between ELISA antibody titres and active protection in buffaloes. There also appeared to be a relationship between cutaneous delayed-type hypersensitivity and active protection in buffaloes. Preliminary analysis of the antibody isotype distribution in the pre-challenge sera of 2 buffaloes vaccinated with the oil adjuvant vaccine revealed predominance of IgG1 and IgG2 subclasses whose role in protection against haemorrhagic septicaemia was not eludicated.

Some plant foods viz. bottlegourd, carrot, cauliflower, cabbage, green bengalgram, pea, apple, plum, guava, karonda, blackgram husk and lentil husk were analysed for their dietary fibre components. The total dietary fibre contents of these foods varied from 14.68 to 78.21 percent on dry matter basis. As compared to fruits and vegetables, the husks had higher amount of total dietary fibre. Cellulose represented as the major fibre constituent in most of the foods whereas, husks were observed to be good sources of hemicellulose. All foods were low in pectin and lignin contents except guava.

A case of fauntail naevus in a teenaged girl with radiological evidence of bifid vertebrae without any neurological, urological or orthopaedic complications is presented.

Targeting Tgf-Beta I With The Transforming Growth Factor Receptor Type I Kinase Inhibitor, Ly2157299, Modulates Stemness-Related Biomarkers In Hepatocellular Carcinoma

Nestin is an intermediate filament protein expressed in undifferentiated cells during the development of brain and is considered as a marker for neuroepithelial stem cells. Expression of this protein in various CNS tumour cells suggests the possibility of existence of tumour stem cell modulating the evolution. We carried out an immunohistochemical study to demonstrate the expression of nestin and its co-expression with neuronal and glial intermediate filament and correlate with the grade of malignancy.Formalin fixed, paraffin processed sections from two human foetuses, 16 brain tumours of both neuronal and glial lineage and two metastatic tumours were immunostained with polyclonal antibody to nestin. Serial sections from primary brain tumours were also stained with monoclonal antibody to neurofilament (NF) and glial fibrillary acidic protein (GFAP). Fluorescent double labeling was carried out on four cases using laser confocal microscopy, to document co-localization of nestin with other intermediate filaments in the tumour cells.Nestin expression was observed along the paraventricular zone of human foetuses and in brain tumours of both glial and neuronal lineage, of both high and low grades of malignancy. In addition, mature dysplastic spinal motor neurons adjacent to tumour and cerebellar Purkinje cells also expressed nestin along with neurofilament.Nestin expression was noted in both low and high grade brain tumours and dysplastic neurons and did not parallel the malignant grade of the tumour. The expression of nestin in tumour cells and dysplastic neurons suggests aberrant expression of antigenically primitive proteins in cells to facilitate remodelling of the cell and migration. More studies are needed to elucidate the concept.

Pulmonary tuberculosis (PTB) patients enrolled for treatment at government health facilities in a sub-district of Thiruvallur district, Tamil Nadu, India.To determine the drug susceptibility profile among PTB patients admitted to treatment according to the Revised National Tuberculosis Control Programme (RNTCP).From May 1999 to December 2003, two additional sputum samples were collected from all patients at the start of anti-tuberculosis treatment under DOTS and were transported to a central laboratory for Mycobacterium tuberculosis culture and drug susceptibility testing (DST).DST results were available for 1603 new sputum smear-positive patients; 85% of patients had organisms fully susceptible to streptomycin (S), isoniazid (H) and rifampicin (R), 10.4% any resistance to H and 1.7% to HR. Of 443 patients with history of previous anti-tuberculosis treatment, 59% had organisms susceptible to S, H and R, 37% had any resistance to H and 11.7% to HR.The DST profile showed that the vast majority of patients have drug-susceptible organisms, and that currently recommended regimens under the RNTCP would be effective in the treatment of TB.

Crohn's disease (CD) and tuberculosis (TB) of the gastrointestinal tract pose major diagnostic problems for clinicians where these conditions coexist. Clinically and radiologically, the diseases are similar. In the West, TB is considered in the differential diagnosis of all suspected cases of CD, particularly among Asian migrants. Earlier age of presentation, perianal disease and enteric fistulae favour a diagnosis of CD. Aphthoid ulceration, pseudopolyps and filiform mucosa at endoscopy are suggestive of CD and a negative tuberculin test us useful. The final diagnosis depends largely on histopathology and the presence or absence of acid fast bacilli. Tuberculosis is more common in developing countries and intestinal TB frequently coexists with pulmonary tuberculosis. TB is known to affect all age groups and fistulous communication, although uncommon, does occur. In addition to radiology and endoscopy, laparotomy may be required to establish the diagnosis. In developing countries, CD is uncommon and remains largely a diagnosis of exclusion. A trial of anti-tuberculosis therapy may often be prescribed before definitely diagnosing CD. The development of molecular biology techniques had led to a revival of interest in mycobacteria as a possible aetiological agent in CD. DNA from Mycobacterium paratuberculosis and Mycobacterium kansaii have both been identified in CD cases but the significance of this finding has not been established. However, in the near future polymerase chain reaction will become increasingly useful in differentiating CD from intestinal TB because it allows the amplification and identification of very small quantities of mycobacterium DNA.

Pseudomonas strain MR1 isolated from the coastal waters of Bay of Bengal was found to resist Hg, As, Cd, Cu, Zn and Pb. It efficiently detoxified both organic and inorganic mercuric compounds to non toxic metallic mercury by an inducible enzyme, mercuric reductase. Its resistance to arsenic might be due to energy-dependent arsenate efflux system. Cadmium was detected intracellularly and in the surrounding medium. The bacterium accumulated copper and lead intracellularly.

SUMMARY objective To estimate the half-life of growth hormone In young adult patients with type I (insulin-dependent) diabetes mellitus following bolus injection and prolonged exposure for the purpose of deconvolution analysis of plasma growth hormone profiles to determine growth hormone secretory rates design In the bolus study, an intravenous bolus injection of 100 mU of biosynthetic human growth hormone was given while endogenous growth hormone was suppressed by a continuous Infusion of somatostatin under three different glucose clamp conditions: normoglycae-mla (5 mmol/l) with normoinsulinaemla (65 pmol/l); hyperglycaemia (12 mmol/l) with normofnsulinaemia; and normoglycaemia with hyperlnsullnaemia (360 pmol/l). In the infusion study, the effect of prolonged and repeated growth hormone exposure upon the growth hormone half-life was estimated. Three pulses of 60 minutes growth hormone infusion (6 mU/kg/pulse) two hours apart under euglycaemic somatostatin suppression were applied. PATIENTS Six young adult patients with type I (insulin-dependent) diabetes mellitus were studied in both the bolus and the infusion study results Mean GH half-lives by mono-exponential analysis were not significantly different remaining unaltered by the short-term metabolic changes of hyperglycaemia and hyperinsullnaemla. Data were therefore pooled yielding an overall mean GH half-life of 13·6 minutes (range 11·9–19·4). Applying a bl-exponentlal model mean GH half-lives were 3·1 minutes (range 2·5–5·9) for the rapid phase of distribution of the hormone and 13·4 minutes (range 9·6–16·9) for the decay of GH from the circulation The GH half-life during the infusions studies did not vary with repeated exposure but was Significantly longer (mean half-life of 25·7 minutes; range 19·4–37·1) than during the bolus studies (P > 0·001). conclusions The half-life of exogenous r-hGH is not affected by glucose or insulin concentrations but increases after prolonged GH exposure in young adults with type I (Insulin-dependent) diabetes mellitus

Hepatocellular carcinoma is difficult to treat, primarily because the underlying molecular mechanisms driving clinical outcome are still poorly understood. Growing evidence suggests that the tissue microenvironment has a role in the biological behavior of the tumor. The main clinical issue is to identify the best target for therapeutic approaches. Here, we discuss the hypothesis that the entire tissue microenvironment might be considered as a biological target. However, the tissue microenvironment consists of several cellular and biochemical components, each of which displays a distinct biological activity. We discuss the major components of this environment and consider how they may interact to promote tumor/host crosstalk.