Chemical sympathectomy impairs bone resorption in rats: a role for the sympathetic system on bone metabolism

The possibility that the nervous system may control bone metabolism has been raised, as neuromediators physiologically conveyed by sympathetic fibers (eg, vasoactive intestinal peptide) influence bone resorption in vitro. In this study, the sympathetic system was inactivated by treating rats with guanethidine (40 mg/kg/day), a sympathetic neurotoxic, for 21 days, after which a wave of osteoclastic resorption was induced along the mandibular buccal cortex. The effects of denervation were assessed 4 days later (corresponding to the peak of resorption in this model). The rats exhibited ptosis soon after starting guanethidine, proving the success of the sympathectomy. This was associated with a significant increase in calcitonin gene-related peptide- (+54%, p < 0.02) and substance P-immunoreactive sensory fibers (+29%,p < 0.02), a known effect of sympathectomy. For the quantitation of the bone parameters, the study zone was divided into a juxta-osseous alkaline phosphatase-positive osteogenic compartment and a nonosteogenic compartment. In the osteogenic compartment, the resorption surface was reduced by 56% (p < 0.001) in the treated animals, together with a fall in the number of osteoclasts (-25%,p < 0.05) and impaired osteoclast access to the bone surface. Tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear preosteoclasts were found only in this compartment; they were reduced by 43% (p < 0.05) by the sympathectomy. No change in non-specific esterase (NSE)+ osteoclast precursors was found. In the nonosteogenic compartment, vasodilation was the only effect of sympathectomy (+80%,p < 0.05); in particular, the number of NSE+ cells was not modified. Our results indicate that: (1) interactions of NSE+ precursors with osteogenic cells are required for their differentiation into TRAP+ preosteoclasts; (2) the sympathetic nervous system is not involved in osteoclast precursor recruitment; but (3) has a significant effect on resorption by inhibiting preosteoclast differentiation and disturbing osteoclast activation. These data suggest that depletion of sympathetic mediators may disturb osteogenic cell-mediated osteoclast differentiation.     

Frequency of large CFTR gene rearrangements in Italian CF patients

In most populations, an appreciable fraction of cystic fibrosis transmembrane regulator (CFTR) gene mutations in patients affected by cystic fibrosis (CF) cannot be identified, and large gene rearrangements might be missed by standard analyses. We have searched large gene rearrangements in a sample of 25 North East Italian CF patients who, after an extensive gene analysis of 188 patients, still bear one or two unidentified CF mutations. A systematic gene screening by quantitative multiplex PCR of short fluorescent fragments was performed. Overall, 5/26 (19.2%) rearranged alleles were detected, bearing mutation 3120+1Kbdel8.6Kb (three patients), and c.4_IVS1+69del119bpins299bp (two patients). These mutations were observed in compound heterozygotes with F508del or termination mutations, and a pancreatic insufficient form of CF. These findings confirm the frequency of CFTR gene rearrangements recently observed in French CF patients.     

Mutations in the SPINK1 gene in idiopathic pancreatitis Italian patients

Idiopathic chronic and acute recurrent pancreatitis (IP) have been associated with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Mutations in the serine protease inhibitor Kazal 1 (SPINK1) have been described in some idiopathic chronic patients and it has been suggested that mutations in this gene could be responsible for a loss of trypsin inhibitor function. In this study, the 5'UTR region, and the four exons and exon-intron boundaries of the SPINK1 gene in 32 IP patients have been analyzed. Three IP patients (9.3%) and one control/100 carried the N34S mutation of the SPINK1 gene (Fisher's exact test, P=0.044). No other mutation that could be associated with an altered function of the SPINK1 protein was observed. The N34S mutation was present in two patients who carried the CFTR-IVS8 5T variant and in one who carried the L997F variant in the CFTR gene. The association of SPINK1 with CFTR gene mutations in IP patients is statistically significant (3/32 IP cases and 0/100 control individuals carrying mutations in both genes; Fisher's exact test P=0.01).     

Identification of novel mutations in patients with Shwachman-Diamond syndrome

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disease, mainly characterized by exocrine pancreatic insufficiency, hematological dysfunction and skeletal abnormalities. The SDS disease locus was mapped to chromosome 7q11 and disease-associated mutations were reported in the Shwachman-Bodian-Diamond syndrome (SBDS) gene. SBDS is a member of a highly conserved protein family with putative orthologs in diverse species including archaea and eukaryotes. It is widely expressed in many tissues and its function is still unknown. In the present study we analyzed the genotype of 15 unrelated Italian SDS patients. After sequencing the whole coding region we were able to complete all genotypes of the SDS patients tested. A total of eleven distinct mutations were identified. The most frequent mutations are due to gene conversion events between SBDS and its unprocessed pseudogene, named SBDSP. We described four new gene conversions involving exon 2 and three novel mutations that are not a result of gene conversion events. In two out of the fifteen cases, the family analysis evidenced an apparently unexpected inheritance of SDS alleles between parents and affected children. In the first case we found a new large gene conversion event, that caused the failure of the amplification of the father's allele and in the second what could be explained as a de novo gene conversion. Both cases have important implications for genetic counseling and molecular genetic analysis. In a disorder caused by gene conversions of variable extension these findings emphasize the necessity of testing patient's parents and the significance of the choice of primers.     

Dense fibrillar collagen matrices sustain osteoblast phenotype in vitro and promote bone formation in rat calvaria defect

Two pure collagen materials were prepared from acidic collagen solutions at 5 and 40?mg/mL. Benefits of collagen concentration on bone repair were evaluated in vitro with human calvaria cells and in vivo in a rat cranial defect. Both materials exhibited specific structures, 5?mg/mL was soft with an open porous network of fibrils; 40?mg/mL was stiffer with a plugged surface and bundles of collagen fibrils. Osteoblasts seeded on 5?mg/mL formed an epithelioid layer with ultrastructural characteristics of mature osteoblasts and induced mineralization. Numerous osteoblasts migrated inside 5?mg/mL, triggering reorganization of their actin cytoskeleton, whereas on 40?mg/mL osteoblasts remained in a resting state. In rat calvaria defects, both materials induced active bone formation. Dual-energy X-ray absorption bone area measures after 4 weeks averaged 84.0% with 5?mg/mL, 88.4% with 40?mg/mL, and 36.7% in the controls (p?相似文献   

Should dentists become 'oral physicians'? No, dentistry must remain dentistry

Dentistry is not an allied health profession. It is not a paramedical profession. It is time that dentistry be recognized as the profession that offers patients some of the most complex surgery performed on the human body--namely, restorative dentistry and rehabilitation of the masticatory system. Dentistry is the only anatomically focused health care profession that is university-based and for which primary care responsibility is maintained by the profession. An inferiority complex about what it means to be a dentist has served only to confuse the public and bring us further from our goal of improving the health of all our patients. This inferiority complex is driven by the public and the medical profession, neither of which understands how dentistry fits into overall health care. It is essential that every academic health center have oral health education as an integrated part of health care education for dentists, physicians, nurses, allied dental personel, physical therapists, psychologists and all who receive university-based health care education. In this way, all the health professions and the public will see dentistry and oral health as essential to patients' overall health. The idea of emulating those who do not have the strength of basic-science education, practice complexity, surgical skills or community status by seizing a new title will not elevate the profession for the future. The public knows what a dentist is. It is our task to inform the public about the capabilities of dentists and the value of oral health and our profession. We can accomplish this best by assuring that our profession's name, "dentistry," is understood to represent one of the world's most accomplished surgical endeavors, one that is thoroughly integrated into the fabric of health care. Thus, good oral health will be thoroughly integrated into what it means to be healthy.     

Pancreatic phenotype in infants with cystic fibrosis identified by mutation screening.

OBJECTIVE: To determine the pancreatic phenotype of infants with cystic fibrosis (CF) diagnosed in the first week of life by a combined immunoreactive trypsin/mutation screening program. DESIGN: A prospective evaluation of pancreatic function in infants with CF at the time of neonatal diagnosis and up to the age of 12. SETTING: Two different centres (Verona, Italy and Westmead, Australia) to enable comparison of results between two regions where <60% or > or =90% of patients, respectively, have at least one single DeltaF508 a mutation. Patients: 315 children with CF including 149 at Verona and 166 at Westmead. INTERVENTIONS: Fat balance studies over 3-5 days and pancreatic stimulation tests with main outcome measures being faecal fat or pancreatic colipase secretion. Patients with malabsorption are pancreatic insufficient (PI) or with normal absorption and pancreatic sufficient (PS). RESULTS: 34 infants (23%) at Verona and 46 (28%) at Westmead were PS at diagnosis. 15% of those with two class I, II or III "severe" mutations and 26/28 (93%) of those with class IV or V mutations were PS at this early age. Of the 80 infants with PS, 20 became PI before the age of 12. All 20 had two severe mutations. CONCLUSION: Neonatal mutational screening programs for CF are less likely to detect PS patients with non-DeltaF508 mutations. Of PS patients who are detected, those with two severe class I, II or III mutations are at particularly high risk of becoming PI during early childhood.