Analysis of polycaprolactone scaffolds fabricated via precision extrusion deposition for control of craniofacial tissue mineralization.

OBJECTIVES: Recurrence of cranial bone fusion following surgical resection in craniosynostosis patients commonly requires additional surgical procedures. Surgical implantation of engineered 3D scaffolds that control tissue mineralization could be utilized to diminish recurrence of fusion. This study investigated the ability of composite scaffolds to control tissue mineralization when cultured in vitro. SETTING AND SAMPLE POPULATION: Precision-engineered scaffolds with calvarial cells were cultured in vitro at the Department of Orthodontics and Pediatric Dentistry, University of Michigan. MATERIAL & METHODS: Polycaprolactone (PCL) scaffolds were fabricated using a novel precision extrusion deposition technique. Polyethylene glycol (PEG) hydrogel was coated onto select scaffolds to inhibit mineralization. MC3T3E1(C4) calvarial cells were cultured with scaffolds in media containing ascorbate and phosphate to promote osteoblast differentiation and mineralization. Scaffolds were assayed for osteoblast differentiation by alkaline phosphatase assay. Scaffolds were assayed for mineralization by nano-computed tomography (nano-CT) and by von Kossa staining of histologic sections. RESULTS: MC3T3E1(C4) cells differentiated into osteoblasts and formed mineral when cultured on uncoated PCL scaffolds. MC3T3E1(C4) cells were significantly diminished in their ability to differentiate into osteoblasts when cultured on hydrogel-coated scaffold. CONCLUSION: Results of this study indicate that this novel printing technology can be used to fabricate 3D scaffolds to promote and inhibit tissue mineralization in a region-specific manner. Future studies are needed to establish utility of such scaffolds in vivo.

Cancer mortality among Chinese chrysotile asbestos textile workers.

To determine mortality associated with exposure to chrysotile asbestos, a cohort of asbestos workers from an asbestos textile factory in China was followed prospectively from 1972 to 2008. A total 577 workers were successfully followed, achieving a follow-up rate of 98.5% over 37 years. Employment data and smoking information were obtained from factory and individual workers. Vital status was ascertained from factory personnel records and the municipal death registry. Workers were categorized into high, medium and low exposure groups in terms of their job titles and workshops. Follow-up generated 17,508 person-years, with 259 deaths from all causes, 96 all cancers and 53 lung cancers and 2 mesotheliomas. The highest cancer mortality was observed in the high exposure group, with 1.5-fold age-adjusted mortality from all cancers and 2-fold from lung cancer compared to the low exposure group. Age and smoking adjusted hazard ratio in the high exposure group was 2.99 (95%CI, 1.30, 6.91) for lung cancer and 2.04 (1.12, 3.71) for all cancers. Both smokers and nonsmokers at the high exposure level had a high death risk of lung cancer, with a clearer exposure-response trend seen in smokers. This study confirmed increased mortality from lung cancer and all cancers in asbestos workers, and the cancer mortality was associated with exposure level.

Pituitary adenylate cyclase activating polypeptide as a novel hypophysiotropic factor in fish.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel member of the secretin-glucagon peptide family. In mammals, this peptide has been located in a wide range of tissues and is involved in a variety of biological functions. In lower vertebrates, especially fish, increasing evidence suggests that PACAP may function as a hypophysiotropic factor regulating pituitary hormone secretion. PACAP has been identified in the brain-pituitary axis of representative fish species. The molecular structure of fish PACAP is highly homologous to mammalian PACAP. The prepro-PACAP in fish, however, is distinct from that of mammals as it also contains the sequence of fish GHRH. In teleosts, the anterior pituitary is under direct innervation of the hypothalamus and PACAP nerve fibers have been identified in the pars distalis. Using the goldfish as a fish model, mRNA transcripts of PACAP receptors, namely the PAC1 and VPACI receptors, have been identified in the pituitary as well as in various brain areas. Consistent with the pituitary expression of PACAP receptors, PACAP analogs are effective in stimulating growth hormone (GH) and gonadotropin (GTH)-II secretion in the goldfish both in vivo and in vitro. The GH-releasing action of PACAP is mediated via pituitary PAC1 receptors coupled to the adenylate cyclase-cAMP-protein kinase A and phospholipase C-IP3-protein kinase C pathways. Subsequent stimulation of Ca2+ entry through voltage-sensitive Ca2+ channels followed by activation of Ca2+-calmodulin protein kinase II is likely the downstream mechanism mediating PACAP-stimulated GH release in goldfish. Although the PACAP receptor subtype(s) and the associated post-receptor signaling events responsible for PACAP-stimulated GTH-II release have not been characterized in goldfish, these findings support the hypothesis that PACAP is produced in the hypothalamus and delivered to the anterior pituitary to regulate GH and GTH-II release in fish.

Hypophysiotropic action of pituitary adenylate cyclase-activating polypeptide (PACAP) in the goldfish: immunohistochemical demonstration of PACAP in the pituitary, PACAP stimulation of growth hormone release from pituitary cells, and molecular cloning of pituitary type I PACAP receptor.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the glucagon/secretin peptide family, and its molecular structure is highly conserved in vertebrates. In this study, the functional role of PACAP in regulating GH release in the goldfish was investigated. Using immunohistochemical staining, nerve fibers with PACAP immunoreactivity were identified in the vicinity of goldfish somatotrophs, suggesting that this neuropeptide may influence GH release in the goldfish. The direct regulatory action of PACAP on GH secretion was demonstrated in vitro in perifused goldfish pituitary cells. PACAPs (0.01 nM to 1 microM) from different species, including ovine PACAP27, ovine PACAP38, frog PACAP38, zebra fish PACAP27, and zebra fish PACAP38, were all effective in stimulating GH release with ED50 values of 8.9 +/- 3.5, 3.3 +/- 1.6, 14.4 +/- 3.5, 15.4 +/- 4.1, and 1.4 +/- 0.2 nM, respectively. Similar concentrations of vasoactive intestinal polypeptide (VIP), a peptide related to PACAP, was not effective in this respect. In addition, the GH-releasing action of ovine PACAP38 (10 nM) was inhibited by the PACAP antagonist PACAP(6-38) (10 microM), but not by the VIP antagonist [4-Cl-D-Phe6,Leu17]VIP (10 microM). The pharmacology of these GH responses is consistent with the mammalian type I PACAP receptors, suggesting that a similar receptor subtype is present in the goldfish pituitary and mediates the GH-releasing action of PACAP. To establish the structural identity of this goldfish PACAP receptor, a complementary DNA (cDNA) clone sharing a high degree of sequence homology with mammalian type I PACAP receptors was isolated from a goldfish pituitary cDNA library. This cDNA was 5.2 kb in size with a 1.4-kb open reading frame and encoded a 465-amino acid protein with the typical structure of a 7-transmembrane domain-containing, G protein-coupled receptor. Functional expression of this cDNA in COS-7 cells revealed that this fish type I PACAP receptor could be activated by ovine PACAP27 and PACAP38 to increase cAMP synthesis with ED50 values of 2.4 +/- 0.8 and 4.2 +/- 1.2 nM, respectively. Other structurally related peptides, including VIP (100 nM), GH-releasing hormone (100 nM), glucagon (100 nM), secretin (100 nM), gastric inhibitory polypeptide (100 nM), and PTH (100 nM), were not effective in altering cAMP production. Using Northern blot and RT-PCR, messenger RNA transcripts of this PACAP receptor were identified in the brain, heart, and pituitary of the goldfish. These results, taken together, support the hypothesis that PACAP functions as a novel GH-releasing factor in the goldfish through activation of type I PACAP receptors.

Body mass index reference curves for Chinese children.

The Hong Kong Growth Survey 1993 provided data for the construction of reference curves for body mass index (BMI) of Chinese children from birth to 18 years. Data on weight and height was obtained from 11797 boys and 12168 girls. The LMS method was used to smooth the percentile curves. These curves showed a definite physiological rising pattern to a peak at 6 months, then fell to a trough at 6 years, before another rise towards adulthood. Compared to published reports from the US, Britain, France and Sweden, Hong Kong Chinese children, particularly the girls, were less obese. In the first 2 years median curves of Hong Kong Chinese were similar to those of the Japanese.

Secular changes in standing height, sitting height and sexual maturation of Chinese--the Hong Kong Growth Study, 1993.

In 1993 a territory-wide cross-sectional growth survey on 25,000 Chinese children from birth to 18 years was performed in Hong Kong. Compared to the last growth survey in 1963, definite secular changes were observed. There was an increase of final adult standing height of 3.6 cm in boys and 2.7 cm in girls, in which 1.8 cm and 0.5 cm respectively for boys and girls was accounted for by the sitting height. Thus most of the height increase had occurred in the leg length in girls, but in boys only half of it. The height difference was more marked during the pubertal years because secular change had brought about an earlier sexual maturation, including an advancement of median menarcheal age by 0.5 year, coupled with an earlier growth spurt. This paper also provides the first growth standards for Chinese from birth to 18 years, with percentile charts on both standing height and sexual maturation in boys and girls.

Weight-for-age and weight-for-height references for Hong Kong children from birth to 18 years.

OBJECTIVE: Childhood obesity is an emerging problem in Asia. Sequential monitoring of the growth of an individual can detect a change in body fatness, provided there are ethnically appropriate growth references. METHODOLOGY: A territory wide cross-sectional growth survey of Hong Kong on 24709 individuals from the age of newborn to 18 years was performed in 1993. Weight-for-age and weight-for-height percentile charts were prepared separately for boys and girls. RESULTS: There was an average increase of 8.5 kg and 5.1 kg in the 18 year old boys and girls, respectively, compared to those surveyed 30 years ago. The percentile curves between 6 and 18 years were similar to those of Singapore. Weight-for-height percentile curves were close to those of America in the prepubertal years. CONCLUSIONS: These Hong Kong growth standards for weight-for-age and weight-for-height are important tools for the assessment of nutritional status of an individual and for monitoring changes in nutritional status of the population.

Shared antenatal care between family health services and hospital (consultant) services for low risk women.

Four thousand four hundred and seventy-two patients were recruited into a project to test the efficacy of a Shared Care System in the management of low risk antenatal patients. The patients were scored according to a simple point scoring system. Three thousand three hundred and fourty-seven (74.8%) were scored as low risk. Fifty point two percent (1,682) of these low risk patients received the conventional system of care and acted as controls; while 49.8% (1,665) received shared care, where they were seen jointly by midwives, general doctors and hospital specialists. It was found that with the use of shared care, there was a significant decrease in workload to the hospital specialty clinics. Not only was the antenatal diagnostic rate of intrauterine growth retardation (IUGR) significantly improved, but the mean gestations at which IUGR, malpresentations, and pregnancy induced hypertension were diagnosed were also significantly earlier. The number of antenatal cardiotocographs performed, as well as the number of hospital admissions and mean duration of stay were decreased in the study group. The overall cost savings to the hospital was calculated if the shared care system was generally adopted.