The local pharmacokinetics of ³H-ropivacaine and ¹⁴C-lidocaine after maxillary infiltration anesthesia in rats

The effects of infiltration anesthesia with ropivacaine on the dental pulp are considered to be weak. This may be partly associated with its permeation into the oral tissue. With the objective of investigating the local pharmacokinetics of ropivacaine and lidocaine following infiltration anesthesia, we injected (3)H-ropivacaine or (14)C-lidocaine to the palatal mucosa in rats, measured distributions of radioactivity in the maxilla, and compared the local pharmacokinetics of these agents. The animals were sacrificed at various times and the maxillas were removed. The palatal mucosa and maxillary nerve were resected, and the bone was divided into 6 portions. We measured radioactivity in each tissue and calculated the level of each local anesthetic (n = 8). Lidocaine diffused to the surrounding tissue immediately after the injection, whereas ropivacaine tended to remain in the palatal mucosa for a longer period. Lidocaine showed a higher affinity for the maxillary bone than ropivacaine. There was a correlation between the distribution level of local anesthetics in the maxillary bone and that in the maxillary nerve. The lower-level effects of infiltration anesthesia with ropivacaine on the dental pulp may be because ropivacaine has a high affinity for soft tissue, and its transfer to bone is slight.     

A case of extragingival peripheral ameloblasotoma in the buccal mucosa

Peripheral ameloblastomas (PAs) of the extragingival areas are extremely rare. To the best of our knowledge, only five cases of extragingival PA have been reported. We present here a sixth case of extragingival PA of the buccal mucosa in an 80-year-old male. The tumor was surgically removed by blunt dissection and there is no evidence of recurrence for 7 months. We also discuss here the clinical characteristics, the origin, and the management of the tumor by reference to the relevant literature.     

Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo

Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery for siRNAs toward treatment of bone-metastatic cancer. Accordingly, we report here that i.v. injection of GL3 luciferase siRNA complexed with atelocollagen showed effective reduction of luciferase expression from bone-metastatic prostate tumor cells developed in mouse thorax, jaws, and/or legs. We also show that the siRNA/atelocollagen complex can be efficiently delivered to tumors 24 h after injection and can exist intact at least for 3 days. Furthermore, atelocollagen-mediated systemic administration of siRNAs such as enhancer of zeste homolog 2 and phosphoinositide 3'-hydroxykinase p110-alpha-subunit, which were selected as candidate targets for inhibition of bone metastasis, resulted in an efficient inhibition of metastatic tumor growth in bone tissues. In addition, upregulation of serum IL-12 and IFN-alpha levels was not associated with the in vivo administration of the siRNA/atelocollagen complex. Thus, for treatment of bone metastasis of prostate cancer, an atelocollagen-mediated systemic delivery method could be a reliable and safe approach to the achievement of maximal function of siRNA.     

IIIc isoform of fibroblast growth factor receptor 1 is overexpressed in human pancreatic cancer and enhances tumorigenicity of hamster ductal cells

BACKGROUND & AIMS: Fibroblast growth factors (FGFs) are mitogenic polypeptides that signal via FGF receptors (FGFRs). Pancreatic ductal adenocarcinomas (PDACs) overexpress multiple FGFs, implying a potential for growth modulation. In this study we investigated the importance of the IIIc splice variant of FGFR-1 (FGFR-1 IIIc) in PDAC. METHODS: Expression of FGFR-1 IIIc was determined by a ribonuclease protection assay in pancreatic cancer cell lines and in tissues. In situ hybridization was used to localize FGFR-1 IIIc messenger RNA (mRNA) in pancreatic tissues. A cDNA encoding FGFR-1 IIIc was stably transfected into the well-differentiated TAKA-1 pancreatic ductal cell line that is not responsive to FGF5 and does not express FGFR-1. RESULTS: FGFR-1 IIIc was expressed in 5 of 7 pancreatic cancer cell lines and in the majority of the cancer cells in 4 of 7 PDAC samples. In vitro, TAKA-1 cells stably transfected with FGFR-1 IIIc exhibited increased basal growth; enhanced basal tyrosine phosphorylation of FGFR substrate-2 (FRS2), Shc, and phospholipase Cgamma; and increased activation of mitogen-activated protein kinase (MAPK). PD98059, an inhibitor of MAPK, suppressed the basal growth of parental and transfected clones, but the effect was more marked in clones expressing FGFR-1 IIIc. In vivo, tumor formation in nude mice was dramatically enhanced with FGFR-1 IIIc transfected (20 of 20) in comparison with sham transfected (0 of 10) cells. CONCLUSIONS: Our data indicate that FGFR-1 IIIc is expressed in human pancreatic cancer cells, promotes mitogenic signaling via the FRS2-MAPK pathway, and has the potential to enhance pancreatic ductal cell transformation.     

Cost-utility analysis of a one-time supervisor telephone contact at 6-weeks post-partum to prevent extended sick leave following maternity leave in The Netherlands: results of an economic evaluation alongside a randomized controlled trial

Background  

Working women of childbearing age are a vital part of the population. Following childbirth, this group of women can experience a myriad of physical and mental health problems that can interfere with their ability to work. Currently, there is little known about cost-effective post-partum interventions to prevent work disability. The purpose of the study was to evaluate whether supervisor telephone contact (STC) during maternity leave is cost-effective from a societal perspective in reducing sick leave and improving quality-adjusted life years (QALYs) compared to common practice (CP).     

Pain and emotion: New research directions

Originally published in J Clin Psychol 57: 587–607, 2001. Through an oversight, Jamie Studts had previously not been listed as an author of this article in the special issue entitled “Psychological Treatment of the Patient with Chronic Disease.” The editors apologize for the omission.     

Genetic polymorphisms of killer cell immunoglobulin-like receptors are associated with susceptibility to psoriasis vulgaris

To elucidate the association between killer cell immunoglobulin-like receptors (KIRs) and psoriasis vulgaris (PV), we typed 14 KIR genes in 96 Japanese cases and 50 healthy controls using PCR with sequence-specific primers (PCR-SSP). Here we report an interesting association between certain KIRs and Japanese cases with PV. The frequencies of KIR2DS1 and KIR2DL5 were significantly increased in PV cases compared with controls (KIR2DS1, 43 of 96 (45%) in cases vs 14 of 50 (28%) in controls; KIR2DL5, 46 of 96 (48%) in cases vs 15 of 50 (30%) in controls, p<0.05 for both), and the frequency of carriage of at least one presumed "B" haplotype, inferred from patterns including KIR2DL2, KIR2DL5, and/or various combinations of activating KIRs, was also statistically increased in the PV cases (53 of 96 (55%) in cases vs 18 of 50 (36%) in controls, p<0.04). The increase in KIR2DS1 has also been observed in psoriatic arthritis, another HLA-Cw6-associated disease (Martin et al, 2002). Accordingly, KIR2DS1 may be a common denominator of both diseases.