Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

Copper,Zinc and Lead Enrichments in Sediments from Guacanayabo Gulf,Cuba, and Its Bioaccumulation in Oysters,Crassostrea rhizophorae

Levels of iron, copper, zinc and lead were determined in sediments and soft tissue of the oyster Crassostrea rhizophorae collected from Guacanayabo Gulf, Cuba. Metal-to-Iron ratio in sediments shows an average enrichment for Cu (5,1), Pb (11,7) and Zn (1,3) in the last 20 years. Metal concentrations found in soft tissue of C. rhizophorae are site dependent. The average biota-sediment accumulation factors (BSAFs) obtained for Fe, Cu and Pb are less than unity in all cases, indicating that only a little fraction of Cu and Pb in the sediments is bioavailable, independently of their enrichments. Zinc has an average BSAF value of 2.4 and may represent a serious impact in the area. The concentrations of zinc and copper in some of the oysters are above typical public health recommended limits.     

Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis

Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.     

Effect of losartan on sodium appetite of hypothyroid rats subjected to water and sodium depletion and water, sodium and food deprivation

The involvement of angiotensin AT1 receptors in sodium appetite was studied in hypothyroid rats treated with the angiotensin II antagonist losartan. Losartan was administered chronically by the oral route or acutely by the subcutaneous route after water and sodium depletion or water, sodium and food deprivation. Three days after addition of losartan to the food at the dose of 1.0 mg x g(-1), the rats significantly reduced (P < 0.02) their spontaneous intake of 1.8% NaCl. Increasing the dose of losartan to 2.0 and 4.0 mg x g(-1) did not reduce NaCl intake; in contrast, the intensity of the sodium appetite gradually returned to previous levels. The simultaneous administration of captopril, an angiotensin converting enzyme inhibitor, and losartan significantly increased (P < 0.05) NaCl intake and after captopril removal NaCl intake returned to the levels observed with losartan treatment alone. The administration of losartan 4 days after the beginning of captopril treatment significantly reduced (P < 0.0001) NaCl intake. Following acute administration of losartan, water- and sodium-depleted rats significantly reduced their NaCl and water intake (P < 0.001). The administration of losartan also induced a significant reduction in NaCl and water intake in water, NaCl and food-deprived rats (P < 0.0001 and P < 0.001, respectively). The present results show that chronic treatment with oral losartan inhibited spontaneous sodium appetite in hypothyroid rats. Continuation of treatment rendered rats resistant to the blockade of AT1 receptors. Water and sodium depletion and water, NaCl and food deprivation induced sodium appetite, which in the short term depends on cerebral angiotensinergic activity mediated by the activation of AT1 receptors.     

Changes in myocardial pyrimidine nucleotide levels following repeated injections of isoproterenol in rats

Changes which might lead to the initiation of cardiac hypertrophy include possible variations in the dynamics of nucleotides. In the experiments reported in this paper, changes in the pool sizes of adenine, uracil and cytosine nucleotides were observed during the initial phase of cardiac overload.Repeated subcutaneous injections of isoproterenol (ISO) (5 mg·kg^–1 body weight, s.c.) were performed so as to produce symmetric cardiomegaly in rats. Under these conditions, the dry weight of the heart, on the fifth day of dialy injections of ISO, had increased by 43% and the RNA concentration by 39%. There was no significant change in the DNA concentration. No further changes in weight or in DNA and RNA concentrations were recorded from the fifth to the tenth day of treatment.Changes in UTP and ATP were carefully monitored during the first days following ISO application. The levels of both nucleotides decreased sharply at first. The ATP level remained below the control value for at least 48 h while the UTP level was rapidly restored and a further increase occurred resulting in a maximal enlargement of 82% after the 12th h. At the same time, the uracil nucleotide pool and the cytosine nucleotide pool had increased by 76% and 101%, respectively, while the adenine nucleotide content of the myocardium remained 15% below control level. Repeated injections of ISO induced effects on ATP and UTP levels which were similar in direction but attenuated.The significance of an increase in the pyrimidine nucleotide pools in relation to nucleic acid synthesis is discussed.     

Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1)

Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced thoracic cavity. In the most common subtype (TD1), femurs are curved, while in TD2, straight femurs are associated with cloverleaf skull. Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene were identified in both subtypes. While TD2 was accounted for by a single recurrent mutation in the tyrosine kinase 2 domain, TD1 resulted from either stop codon mutations or missense mutations in the extracellular domain of the gene. Here, we report the identification of FGFR3 mutations in 25/26 TD cases. Two novel missense mutations (Y373C and G370C) were detected in 8/26 and 1/26 TD1 cases respectively. Both mutations created cysteine residues in the juxta extramembrane domain of the receptor. Sixteen cases carried the previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically homogeneous condition and give additional support to the view that newly created cysteine residues in the extracellular domain of the protein play a key role in the severity of the disease.