A prospective, randomised, controlled, double-blind phase I-II clinical trial on the safety of A-Part® Gel as adhesion prophylaxis after major abdominal surgery versus non-treated group

<p>Abstract</p> <p>Background</p> <p>Postoperative adhesions occur when fibrous strands of internal scar tissue bind anatomical structures to one another. The most common cause of intra-abdominal adhesions is previous intra-abdominal surgical intervention. Up to 74% of intestinal obstructions are caused by post surgical adhesions. Although a variety of methods and agents have been investigated to prevent post surgical adhesions, the problem of peritoneal adhesions remains largely unsolved. Materials serving as an adhesion barrier are much needed.</p> <p>Methods/Design</p> <p>This is a prospective, randomised, controlled, patient blinded and observer blinded, single centre phase I-II trial, which evaluates the safety of A-Part^®Gel as an adhesion prophylaxis after major abdominal wall surgery, in comparison to an untreated control group. 60 patients undergoing an elective median laparotomy without prior abdominal surgery are randomly allocated into two groups of a 1:1- ratio. Safety parameter and primary endpoint of the study is the occurrence of wound healing impairment or peritonitis within 28 (+10) days after surgery. The frequency of anastomotic leakage within 28 days after operation, occurrence of adverse and serious adverse events during hospital stay up to 3 months and the rate of adhesions along the scar within 3 months are defined as secondary endpoints. After hospital discharge the investigator will examine the enrolled patients at 28 (+10) days and 3 months (±14 days) after surgery.</p> <p>Discussion</p> <p>This trial aims to assess, whether the intra-peritoneal application of A-Part^®Gel is safe and efficacious in the prevention of post-surgical adhesions after median laparotomy, in comparison to untreated controls.</p> <p>Trial registration</p> <p>NCT00646412</p

Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia

Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27-fold in pancreatic cancer cells compared to normal ductal cells in a microarray analysis. Given the need for biomarkers in the early diagnosis of pancreatic cancer, we investigated the expression of NGAL in tissues with the objective of examining if NGAL immunostaining could be used to identify foci of pancreatic intraepithelial neoplasia, premalignant lesions preceding invasive cancer. To examine a possible correlation between NGAL expression and the degree of differentiation, we also analysed NGAL levels in pancreatic cancer cell lines with varying grades of differentiation. Although NGAL expression was strongly upregulated in pancreatic cancer, and moderately in pancreatitis, only a weak expression could be detected in the healthy pancreas. The average composite score for adenocarcinoma (4.26±2.44) was significantly higher than that for the normal pancreas (1.0) or pancreatitis (1.0) (P<0.0001). Further, although both well- and moderately differentiated pancreatic cancer were positive for NGAL, poorly differentiated adenocarcinoma was uniformly negative. Importantly, NGAL expression was detected as early as the PanIN-1 stage, suggesting that it could be a marker of the earliest premalignant changes in the pancreas. Further, we examined NGAL levels in serum samples. Serum NGAL levels were above the cutoff for healthy individuals in 94% of pancreatic cancer and 62.5% each of acute and chronic pancreatitis samples. However, the difference between NGAL levels in pancreatitis and pancreatic cancer was not significant. A ROC curve analysis revealed that ELISA for NGAL is fairly accurate in distinguishing pancreatic cancer from non-cancer cases (area under curve=0.75). In conclusion, NGAL is highly expressed in early dysplastic lesions in the pancreas, suggesting a possible role as an early diagnostic marker for pancreatic cancer. Further, serum NGAL measurement could be investigated as a possible biomarker in pancreatitis and pancreatic adenocarcinoma

Patterns of diversification amongst tropical regions compared: a case study in Sapotaceae

Species diversity is unequally distributed across the globe, with the greatest concentration occurring in the tropics. Even within the tropics, there are significant differences in the numbers of taxa found in each continental region. Manilkara is a pantropical genus of trees in the Sapotaceae comprising c. 78 species. Its distribution allows for biogeographic investigation and testing of whether rates of diversification differ amongst tropical regions. The age and geographical origin of Manilkara are inferred to determine whether Gondwanan break-up, boreotropical migration or long distance dispersal have shaped its current disjunct distribution. Diversification rates through time are also analyzed to determine whether the timing and tempo of speciation on each continent coincides with geoclimatic events. Bayesian analyses of nuclear (ITS) and plastid (rpl32-trnL, rps16-trnK, and trnS-trnFM) sequences were used to reconstruct a species level phylogeny of Manilkara and related genera in the tribe Mimusopeae. Analyses of the nuclear data using a fossil-calibrated relaxed molecular clock indicate that Manilkara evolved 32–29 million years ago (Mya) in Africa. Lineages within the genus dispersed to the Neotropics 26–18 Mya and to Asia 28–15 Mya. Higher speciation rates are found in the Neotropical Manilkara clade than in either African or Asian clades. Dating of regional diversification correlates with known palaeoclimatic events. In South America, the divergence between Atlantic coastal forest and Amazonian clades coincides with the formation of drier Cerrado and Caatinga habitats between them. In Africa diversification coincides with Tertiary cycles of aridification and uplift of the east African plateaux. In Southeast Asia dispersal may have been limited by the relatively recent emergence of land in New Guinea and islands further east c. 10 Mya

CAL b, a novel lipocalin associated with chondrogenesis and inflammation

We have previously demonstrated the association of the chicken lipocalin Ex-FABP with cartilage formation and inflammatory responses as a marker of these processes (Descalzi Cancedda et al., Biochim. Biophys. Acta 1482, 127-135, 2000). Here we report the isolation and characterisation of a new lipocalin gene laying upstream the Ex-FABP, thus representing the second member of a possible genomic cluster. This gene contains an open reading frame coding for a polypeptide of about 19 kDa. The amino-acid sequence revealed a conserved lipocalin secondary structure. Tissue distribution of the protein in developing embryos showed a preferential expression in the heart although mRNA transcripts could be detected also in muscle, lung and liver

A chondrogenesis-related lipocalin cluster includes a third new gene, CAL gamma

We have previously reported the modulation, during chondrogenesis and/or inflammation, of two chicken genes laying in the same genomic locus and coding for two polypeptides of the lipocalin protein family, the extracellular fatty acid binding protein (ExFABP) and the chondrogenesis associated lipocalin beta (CALbeta). A third gene, located within the same cluster and coding for a new lipocalin, CALgamma, has been identified and is here characterized. Tissue distribution analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction in chicken embryos shows a ubiquitous expression with predominant levels of mRNA transcripts in the liver and the brain. In the developing tibia, a high expression of CALgamma mRNA was evidenced by in situ hybridization within the pre-hypertrophic and the hypertrophic zones of the bone-forming cartilage. In agreement, dedifferentiated chondrocytes in vitro express the transcripts to the highest level when they re-differentiate reaching hypertrophy. Such peculiar developmental pattern of expression that is analogous to those already described for Ex-FABP and CALbeta suggests that all three proteins may act synergistically in the process of endochondral bone formation

A Chondrogenis related lipocalin cluster includes a third new gene, CALgamma

We have previously reported the modulation, during chondrogenesis and/or inflammation, of two chicken genes laying in the same genomic locus and coding for two polypeptides of the lipocalin protein family, the extracellular fatty acid binding protein (ExFABP) and the chondrogenesis associated lipocalin beta (CALbeta). A third gene, located within the same cluster and coding for a new lipocalin, CALgamma, has been identified and is here characterized. Tissue distribution analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction in chicken embryos shows a ubiquitous expression with predominant levels of mRNA transcripts in the liver and the brain. In the developing tibia, a high expression of CAL-gamma mRNA was evidenced by in situ hybridization within the pre-hypertrophic and the hypertrophic zones of the bone-forming cartilage. In agreement, dedifferentiated chondrocytes in vitro express the transcripts to the highest level when they redifferentiate reaching hypertrophy. Such peculiar developmental pattern of expression that is analogous to those already described for ExFABP and CALbeta suggests that all three proteins may act synergistically in the process of endochondral bone formation. Moreover, like ExFABP and CALbeta, CAL-gamma is also highly induced in dedifferentiated chondrocytes upon stimulation with lypopolysaccharides, indicating that the whole cluster quite possibly is transcriptionally activated not only in physiological morphogenic differentiation but also in pathological acute phase response. (C) 2003 Elsevier Science B.V. All rights reserved