Clinico-pathological aspects of a residual natal tooth: a case report

A Japanese girl was referred to Osaka University Dental Hospital for examination of a tooth-like structure that had erupted following spontaneous exfoliation of a natal tooth in the lower left primary central incisor region. The structure had erupted at 6 months of age, and radiographic and clinical examination showed composition of pulp and dentin, but no enamel. On histological examination, the majority of the dentin area had a tubular dentin-like appearance, while the outer area of the root appeared to be composed of an osteodentin-like substance. Most of the dentin was covered by cementum. These findings suggest that the structure had originated from a developing remnant of the extracted natal tooth, which must have remained in the gingival tissues. We termed this calcified structure a residual natal tooth.     

A mechanism for reducing intraocular pressure in normal volunteers using UF-021, a prostaglandin-related compound]

The mechanism of reduction of intraocular pressure (IOP) and other ocular effects were studies after topical application of prostaglandin (PG) F2 alpha and UF-021, a new PG related compound, in eight normal volunteers. IOP, aqueous humor flow rate and outflow rate were evaluated during a period of four hours after the application. Both PGF2 alpha and UF-021 caused significant and similar IOP reduction for four hours. Neither compound produced any significant change in the aqueous humor flow rate or outflow rate, suggesting the increase of unconventional outflow rate as being the possible mechanism of IOP reduction in normal human eyes.     

多激素分泌性垂体泌乳素腺瘤的激素分泌谱及克隆分析

目的 对多激素分泌性垂体泌乳素腺瘤的克隆状态以及激素分泌谱进行分析。方法 对26例女性垂体泌乳素腺瘤患者（单激素分泌性PRL腺瘤7例，多激素分泌性PRL腺瘤19例）进行肿瘤标本的免疫组化分析，并且提取DNA行HUMARA分析。结果免疫组化分析提示本组多激素分泌性垂体PRL腺瘤具有10种不同的激素分泌谱，现代分子生物学HUMARA克隆分析提示11／13例（85％）多激素分泌性垂体PRL腺瘤为单克隆起源。结论 结果提示垂体泌乳素腺瘤除了分泌泌乳素外，还可以分泌多种垂体激素，而且绝大多数多激素分泌性垂体腺瘤的起源是单克隆性的。     

INTRAOPERATIVE BLEEDING IN ENDOSCOPIC SUBMUCOSAL DISSECTION IN THE STOMACH AND STRATEGY FOR PREVENTION AND TREATMENT

To control intraoperative bleeding is an important key to successful endoscopic submucosal dissection. The distribution of submucosal vessels encountered during the procedure differ in places in the stomach and are roughly categorized into three groups: those located in the antrum, those in the lesser curvature, and those on the anteroposterior corpus wall which consists of oblique muscle layers. Therefore, knowledge of a suitable setting of diathermy and adjusted depth of dissection in the submucosal layer for each site is imperative. The combination of utilizing the distal attachment forced or swift coagulation (trimming with coagulation mode) have enable the treatment with an insulation tipped knife safer.     

Human urotensin-II potentiates the mitogenic effect of mildly oxidized low-density lipoprotein on vascular smooth muscle cells: comparison with other vasoactive agents and hydrogen peroxide.

Human urotensin-II (U-II) is the most potent vasoactive peptide identified to date, and may be involved in hypertension and atherosclerosis. We investigated the effects of the interactions between U-II or other vasoactive agents and mildly oxidized low-density lipoprotein (mox-LDL) or hydrogen peroxide (H2O2) on the induction of vascular smooth muscle cell (VSMC) proliferation. Growth-arrested rabbit VSMCs were incubated with vasoactive agents (U-II, endothelin-1, angiotensin-II, serotonin, or thromboxane-A2) in the presence or absence of mox-LDL or H2O2. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. On interaction with mox-LDL or H2O2, U-II induced the greatest increase in [3H]thymidine incorporation among these vasoactive agents. A low concentration of U-II (10 nmol/l) enhanced the potential mitogenic effect of low concentrations of mox-LDL (120 to 337%) and H2O2 (177 to 226%). U-II at 50 nmol/l showed the maximal mitogenic effect (161%), which was abolished by G protein inactivator (GDP-beta-S), c-Src tyrosine kinase inhibitor (radicicol), protein kinase C (PKC) inhibitor (Ro31-8220), extracellular signal-regulated kinase (ERK) kinase inhibitor (PD98059), or Rho kinase inhibitor (Y27632). Mox-LDL at 5 microg/ml showed the maximal mitogenic effect (211%), which was inhibited by free radical scavenger (catalase), intracellular and extracellular antioxidants (N-acetylcysteine and probucol), nicotinamide adenine dinucleotide phosphate oxidase inhibitor (diphenylene iodonium), or c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results suggested that U-II acts in synergy with mox-LDL in inducing VSMC DNA synthesis at the highest rate among these vasoactive agents. Activation of the G protein/c-Src/PKC/ERK and Rho kinase pathways by U-II together with the redox-sensitive JNK pathway by mox-LDL may explain the synergistic interaction between these agents.     

Strategy for research and development of antifungal agents]

The incidence of deep-seated mycosis has recently been increasing, while the number of clinically available antifungal agents is very limited and each agent has some drawbacks. We focused on the triazole class that is known to have good profiles as antifungal agents. After researching them, we found that CS-758 had excellent profiles in terms of antifungal spectrum, activity, and safety. Until this candidate was obtained, we experienced the following difficulties: (1) In vivo activity did not always reflect in vitro activity. (2) The relationship between in vivo activity and pharmacokinetic profile was important in selecting a candidate as an antifungal agent. (3) Suitable infection-models had to be established to predict clinical efficacy. (4) It was necessary to demonstrate superiority over marketed drugs to develop a novel agent. These experiences give us good ideas for future development of novel antifungal agents.     

LAPAROSCOPIC TREATMENT FOR PERFORATED APPENDICITIS WITH PELVIC ABSCESS

We performed laparoscopic appendectomy and drainage to treat panperitonitis due to perforated appendicitis that occurred in a 28‐year‐old woman. We believe this is an appropriate procedure to treat perforated appendicitis because it is safe and minimally invasive, and faster recovery can be expected than after conventional open appendectomy.     

Covalent binding of rofecoxib, but not other cyclooxygenase-2 inhibitors, to allysine aldehyde in elastin of human aorta.

In rats, it has been reported that rofecoxib, a cyclooxygenase-2 (COX-2) inhibitor, reacts with the aldehyde group of allysine in elastin to give a condensation covalent adduct, thereby preventing the formation of cross-linkages in the elastin and causing degradation of the elastic fibers in aortas in vivo. Acid, organic solvent, and proteolytic enzyme treatments of human aortic homogenate after incubation with [(14)C]rofecoxib demonstrated that most of the radioactivity is covalently bound to elastin. The in vitro covalent binding was inhibited in the presence of beta-aminopropionitrile, D-penicillamine, and hydralazine, which suggested that the aldehyde group of allysine in human elastin was relevant to the covalent binding. The in vitro covalent binding of [(14)C]rofecoxib was significantly decreased by the addition of only nonradiolabeled rofecoxib but not the other COX-2 inhibitors, celecoxib, valdecoxib, etoricoxib, and CS-706 [2-(4-ethoxyphenyl)-4-methyl 1-(4-sulfamoylphenyl)-1H-pyrrole], a novel selective COX-2 inhibitor. All the above COX-2 inhibitors except for rofecoxib had no reactivity with the aldehyde group of benzaldehyde used as a model compound of allysine aldehyde under a physiological pH condition. On the other hand, no retention of the radioactivity of [(14)C]rofecoxib was observed in human aortic endothelial cells in vitro, suggesting that rofecoxib is not retained in aortic endothelial cells in vivo. These results suggest that rofecoxib, but not other COX-2 inhibitors, is capable of covalently binding to the aldehyde group of allysine in human elastin. This might be one of the main causes of cardiovascular events by rofecoxib in clinical situations.