1‐(2‐Hydroxyethyl)‐2‐imidazolidinone,a heparanase and matrix metalloproteinase inhibitor,improves epidermal basement membrane structure and epidermal barrier function

Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage.     

Sudden death from metastatic esophageal cancer to the ventricular septum.

A 67-year-old man was admitted to our hospital due to esophageal cancer. Cancer existed at the lower esophagus and subtotal esophagectomy and lymphadenectomy was performed. The postoperative course was uneventful. Pathological findings revealed moderately differentiated squamous cell carcinoma that metastasized to the abdominal lymph nodes which include the paraaortic lymph nodes. He complained of anorexia three months after the operation and was found to have multiple liver and mediastinal lymph node metastases. He was admitted for chemotherapy. Before starting chemotherapy, he suddenly died without any sign of hemorrhage or respiratory disorder. Autopsy showed metastatic lesions to the heart and mediastinal lymph nodes, liver, thoracic vertebrae, kidney, adrenal gland and heart. Metastatic nodules in the heart were on the ventricular septum where the conducting system exists. No direct invasion from the pericardium was observed. Blockade of the conducting system of the heart was considered to have caused the severe arrhythmia and sudden cardiac arrest.     

Anteroposterior lip positions of the most-favored Japanese facial profiles.

INTRODUCTION: Soft tissue analysis is a basic tool in planning orthodontic treatment. However, the components of a well-balanced Japanese facial profile have not yet been established. The purpose of this study was to assess the most-favored or most well-balanced profile from a series of facial silhouettes with varying anteroposterior lip positions by a group of Japanese orthodontists and a group of young adult Japanese dental students. METHODS: Average female and male profiles were constructed from the profiles of 30 Japanese men and women with normal occlusions. The lips in each average profile were protruded or retruded in 1-mm increments, and the 13 images were arranged with the average profile in the center. Forty two orthodontists and 42 dental students were asked to select the 3 most-favored, well-balanced profiles for each sex and rank them in order of preference. RESULTS: Both the orthodontists and the students preferred a profile with slightly retruded lips. The dental students favored a more retruded lip position for women. The least-favored profile was the most protrusive. CONCLUSIONS: These findings suggest that Japanese orthodontists and young adults prefer a retruded profile, even though Japanese profiles have historically been characterized by more convex facial features.     

Preoperative chemotherapy increases cytokine production after lung cancer surgery.

OBJECTIVE: Many phase II trials have shown that preoperative chemotherapy for lung cancer is feasible but associated with postoperative morbidity and mortality. However, little is known about the effect of preoperative chemotherapy on surgical stress and postoperative complications associated with surgical intervention. We evaluated the effect of preoperative chemotherapy on perioperative inflammatory cytokine production as a surgical stress marker. METHODS: The study group comprised 38 patients undergoing anatomical lung resection and mediastinal nodal dissection for clinical stage IB/II non-small cell lung cancer during the period October 2001-December 2003. Nineteen patients received a single cycle of cisplatin (80 mg/m(2)) and docetaxel (60 mg/m(2)) chemotherapy prior to surgery (neoadjuvant group), and 19 patients underwent surgery without any previous chemotherapy (control group). White blood cell and neutrophil counts and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (GCSF) were determined before surgery and on postoperative days 1 and 3. Postoperative complications were reviewed. Differences were assessed by repeated analysis of variance. RESULTS: Serum concentrations of IL-6 and GCSF rose significantly on postoperative days 1 and 3 in the neoadjuvant group in comparison to concentrations in the control group, but white blood cell count, neutrophil count, and CRP did not differ between the groups. No major complication occurred in either group. CONCLUSIONS: A single cycle of cisplatin and docetaxel chemotherapy followed by surgery can exacerbate overproduction of inflammatory cytokines during the perioperative period in lung cancer patients.     

Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells: an autoradiographic and histologic analysis.

Recent studies have indicated that bone marrow stromal cells (BMSC) have the potential to improve neurologic function when transplanted into animal models of central nervous system disorders. However, how the transplanted BMSC restore the lost neurologic function is not clear. In the present study, therefore, we aimed to elucidate whether BMSC express the neuron-specific gamma-aminobutyric acid (GABA) receptor when transplanted into brain that has been subjected to cerebral infarction. METHODS: The BMSC were harvested from green fluorescent protein-transgenic mice and were cultured. The mice were subjected to permanent middle cerebral artery occlusion. The BMSC or vehicle was transplanted into the ipsilateral striatum 7 d after the insult. Using autoradiography and fluorescence immunohistochemistry, we evaluated the binding of 125I-iomazenil and the expression of GABA receptor protein in and around the cerebral infarct 4 wk after transplantation. RESULTS: Binding of 125I-iomazenil was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. Likewise, the number of the GABAA receptor-positive cells was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. A certain subpopulation of the transplanted BMSC expressed a neuron-specific marker, microtubule-associated protein 2, and the marker protein specific for GABAA receptor in the periinfarct area. CONCLUSION: These findings suggest that BMSC may contribute to neural tissue regeneration through migrating toward the periinfarct area and acquiring the neuron-specific receptor function.     

Apperceptive form visual agnosia caused by anti-TNFalpha therapy to rheumatoid arthritis]

TNFalpha plays an important role as an inflammatory mediator in both several autoimmune diseases and multiple sclerosis. Anti-TNFalpha antibody has been widely used to treat rheumatoid arthritis and Crohn's disease. On the. other hand, anti-TNFalpha antibody treatment increased recurrence rate in clinical trials for multiple sclerosis. We report a patient with rheumatoid arthritis without past history of any neurological disorders, who developed diplopia, ataxia, and visual agnosia specific to line drawing in the course of anti-TNFalpha antibody treatment. MRI studies detected multiple demyelinating lesions in the cerebral white matter and brainstem. The present case indicates that careful observation of neurological symptoms is important in the course of anti-TNFalpha antibody treatment, even in patients without past history of demyelinating diseases.     

Endobronchial aspergillosis and actinomycosis associated with broncholithiasis

Endobronchial aspergillosis or actinomycosis associated with broncholithiasis is extremely rare. Here, we describe two cases of endobronchial aspergillosis and actinomycosis associated with broncholithiasis. The patients underwent pulmonary resection due to massive hemoptysis. These cases reveal that a bronchiolith can potentially induce endobronchial fungal or bacterial infection, even in immunocompetent patients.     

Internalization of Mycobacterium bovis Bacillus Calmette-Guérin into Osteoblast-Like MC3T3-E1 Cells and Bone Resorptive Responses of the Cells against the Infection

Mycobacterium bovis BCG (BCG) is a live vaccine used worldwide against tuberculosis. However, it has unfavourable side effects such as osteitis or osteomyelitis, and these sometimes lead to vertebral caries in some patients as a result of bone resorption. Osteoblasts might play a role in the bone resorption caused by BCG infection, because they are central cells in bone metabolism. Cultured osteoblast-like cell lines (MC3T3-E1) derived from C57BL mice susceptible to BCG infection cells were infected with BCG at several doses. Interestingly, internalization of BCG-enveloped phagosome-like membrane in osteoblast-like cells were observed by transmission electron microscopy (TEM). Owing to infection, the proliferation and alkaline phosphatase activity of the osteoblast-like cells were reduced in a dose-dependent manner. On the other hand, interleukin (IL)-6 production was considerably enhanced by infection. These results suggest that BCG infects osteoblasts, suppressing their proliferation and differentiation and inducing bone resorption, which may be related to osteitis/osteomyelitis and bone caries caused by BCG infection.     

INTRA- AND INTERINDIVIDUAL VARIATION IN THE PHARMACOKINETICS OF TACROLIMUS (FK506) IN KIDNEY TRANSPLANT RECIPIENTS—IMPORTANCE OF TROUGH LEVEL AS A PRACTICAL INDICATOR

Background: Tacrolimus (FK506) is currently used as the primary immunosuppressant in clinical kidney transplantation in some centers. The purpose of this study was to evaluate the pharmacokinetics of this drug and to see if trough level, which has been used widely in therapeutic drug monitoring, can be used as an appropriate substitute for other pharmacokinetic measurement tests. Methods: The blood concentration-time curve was studied in 10 kidney transplant recipients on 26 Occasions after oral dosage of 2 to 18 mg every 12 hours. Whole blood concentration was measured by two-step irnmunoabsorption assay. Methylprednisolone was used as a concomitant immuno-suppressive drug. Results: The blood concentration-time curves showed remarkable interindividual variation. lntraindividual variation was also found, but the degree of variation was slight compared with interindividual variation. On 17 occasions of measurement in one patient, the dose was significantly correlated with trough (r = 0.684). C_max (r = 0.838) and AUC_0–12 (r = 0.817). In nine patients on nine occasions, however, the dose was not significantly correlated with trough (r = 0.351), C_max (r = 0.270) or AUC_0–12 (r = 0.355). t_max ranged from one to four hours (mean + SD; 2.8 + 1.3) and fluctuated in both intra- and interindividual measurements. In spite of a wide variation in the blood concentration-time-curve patterns, a highly significant linear relationship between trough and C_max or AUC_0–12 was observed in both intraindividual (C_max, r = 0.876; AUC_0–12, r = 0.926) and interindividual (C_max, f = 0.943; AUC_0–12, r = 984) measurements. Concluslons: We conclude that trough level is a practical acceptable indicator of the blood levels of tacrolimus, and can be used to monitor blood concentration.