Stromal progenitor cell therapy corrects the wound-healing defect in the ischemic rabbit ear model of chronic wound repair

Chronic wounds create a formidable clinical problem resulting in considerable morbidity and healthcare expenditure. The etiology for wound healing impairment appears to be multifactorial; however, ischemia is a common factor in most types of chronic wounds. Ideal therapy for such wounds would be to correct deficiencies in growth factors and matrix components and provide cellular precursors required for timely wound closure. We hypothesized that stromal progenitor cell (SPC) therapy could correct the ischemic wound-healing defect through both direct and indirect mechanisms. To test this hypothesis, we used the ischemic rabbit ear model of chronic wound healing. We found that treatment of the wounds with SPCs was able to reverse the ischemic wound-healing impairment, with improved granulation tissue formation and reepithelialization compared with vehicle or bone marrow mononuclear cell controls. In vitro, SPCs were found to produce factors involved in angiogenesis and reepithelialization, and extracellular matrix components, providing evidence for both direct and indirect mechanisms for the observed correction of the healing impairment in these wounds. Treatment of ischemic wounds with SPCs can dramatically improve wound healing and provides a rationale for further studies focused on SPCs as a potential cellular therapy in impaired wound healing.     

Influences of angiogenesis and lymphangiogenesis on cancerous invasion in experimentally induced tongue carcinoma

BACKGROUND: Although it is clear that dissemination via the blood system involves angiogenesis, it is uncertain whether tumors also induce lymphangiogenesis or simply invade existing peritumoral vessels. The purpose of this study was to elucidate changes in tumor blood and lymph vessels in cases involving the invasion of squamous cell carcinoma in the oral cavity, and its significance. Blood and lymph vessels densities in tongue carcinomas induced in hamsters were investigated. METHODS: Tongue cancer was induced by abrading the right margin of the tongue of each hamster with an endodontic barbed broach and subsequently applying 1.0% 9,10-dimenthl-1,2-benzanthracene (DMBA) dissolved in acetone, three times a week, at the same site. Fresh frozen sections were prepared and blood vessels stained blue by perfusion with Coomassie Brilliant Blue and lymph vessels stained brown for 5'-nucleotidase. The effects on the blood vessels and lymph vessels were observed. RESULTS: The results showed that blood and lymph vessel densities were greater in the advanced carcinoma tissues than in normal tissue. These were compared in terms of the mode of cancer invasion. As tumor invasion progressed, the blood vessel density decreased but lymph vessel density tended to be higher in high-degree tumor invasion than in low-degree tumor invasion. The expression of vascular endothelial growth factor-C was seen more frequently as tumor invasion progressed. CONCLUSIONS: The present findings indicated that angiogenesis and lymphangiogenesis are affected by cancerous invasion.     

Anti-tumor activity of human recombinant TNF against human malignant glioma cell lines and combined effect with Hu INF-beta

Human TNF was detected fairly recently and at present the anti-tumor activity of human recombinant TNF is being examined against various malignant tumors of human origin. In the present study, we report the anti-tumor activity of recombinant human TNF against human malignant glioma cell lines in vitro and in vivo, in addition to its combined effects with HuIFN-beta. The in vitro study was conducted as follows. Thirteen human glioma cell lines were exposed to 100 U/ml TNF, 1,000 IU/ml HuIFN-beta, or both, and the suppression rate was calculated on days 3, 5 and 7. In the in vivo study, nude mice carrying a human glioma cell line, KMS II, in the subcutaneous tissues were divided into groups and drugs were administered intratumorally as described below. 1) control, 2) TNF 5,000 U single administration, 3) TNF 5,000 U, intermittently administered (once/week for two weeks), 4) TNF 5,000 U, continuously administered (3/week for two weeks), 5) HuIFN-beta 50 X 10(4) IU (3/week for two weeks), and 6) combination of 4) with 5). Results of the in vitro study revealed some suppressive effects on proliferation of tumor cells on day 7 in all 13 glioma cell lines examined with 100 U/ml TNF. And also, especially in 8 of 13 cell lines, the suppression rate was more than 30%. The suppressive effects of TNF were augmented by combined use of HuIFN-beta in all cell lines, giving a range of suppression of 67.8 to 99.3%. The in vivo study revealed that the mean tumor weight ratios (control = 100%) on day 19 (the end of the experiment) were as follows; single administration of TNF: 41.3%, intermittent: 46.7%, continuous: 26.7%, HuIFN-beta: 65.9%, combination: 18.5%. Statistical analysis disclosed significant suppressive effects on tumor proliferation between the control group and 3 TNF-administered groups (single, intermittent, and continuous) and that suppression in the continuously administered group was more severe in comparison with the group given single administration. Moreover, it was suggested that combination therapy with TNF and Hu IFN-beta was more effective than a single therapy with TNF only or HuIFN-beta only. From the results described above, it was found that human recombinant TNF had some cytotoxic effects against human malignant gliomas in vitro and in vivo, although the degree of cytotoxicity was not always higher in comparison with the effects of TNF.     

Freiberg’s Infraction in Identical Twins: A Case Report

Freiberg's infraction is an ostechondrosis of a lesser metatarsal head resulting in degeneration of the metatarsophalangeal joint. Several mechanisms have been suggested in its pathenogenesis. Freiberg first described the entity and believed single impact trauma was the underlying cause. Repetitive biomechanical microtrauma is the most widely accepted etiologic theory. Other factors contributing to its development include aseptic necrosis, ischemia, and a congenital predisposition. We present a case report of Freiberg's infraction occurring in identical twins involving multiple metatarsals in various stages of degeneration. One of the twins was affected unilaterally whereas the other twin was affected bilaterally. Both twins had involvement of the second metatarsal on the same side extremity. The occurrence of Freiberg's infraction in identical twins suggests that an underlying congenital predisposition to the condition may play more of a role than previously considered.     

Improvement of Atrophic Acne Scars with a 1,320 nm Nd:YAG Laser: Retrospective Study

Background. Facial acne scarring has been treated with multiple methods with varying degrees of improvement. Although the 1,320 nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser has been widely used to improve photoaging, studies analyzing its effects on atrophic acne scarring are limited.
Objective. To evaluate the efficacy of a dynamic cryogen-cooled 1,320 nm Nd:YAG laser for the treatment of atrophic facial acne scars in a larger cohort of patients with long-term follow-up.
Methods. Twenty-nine patients (skin phototypes I–IV) with facial acne scarring received a mean of 5.5 (range 2–17) treatments with a 1,320 nm Nd:YAG laser. Objective physician assessment scores of improvement were determined by side-by-side comparison of preoperative and postoperative photographs at a range of 1 to 27 months (mean 10.4 months) postoperatively. Subjective patient self-assessment scores of improvement were also obtained.
Results. Acne scarring was significantly improved by both physician and patient assessment scores. Mean improvement was 2.8 (  p < .05  ) on a 0- to 4-point scale by physician assessment and 5.4 (  p < .05  ) on a 0- to 10-point scale by patient assessment. No significant complications were observed.
Conclusions. Nonablative laser skin resurfacing with a 1,320 nm Nd:YAG laser can effectively improve the appearance of facial acne scars with minimal adverse sequelae.     

P31 The relationship between the relative amount of Porphyromonas gingivalis in saliva and halitosis

Objectives  Porphyromonas gingivalis is one of the microorganisms that most actively produce CH₃SH and we have reported that subjects with P . gingivalis have higher CH₃SH levels than subjects without P .  gingivalis . However, little is known about the relationship between P . gingivalis levels in saliva and the condition of oral malodor. In this study, we evaluated the association between the relative amount of P . gingivalis in saliva and halitosis in mouth air.
Methods  All of the subjects were patients at the Preventive Dentistry and Breath Odor Clinic of Kyushu Dental College, where they received a periodontal examination. Volatile sulfur compounds (VSC: hydrogen sulfide and methyl mercaptan) were measured using gas chromatography. Saliva samples were collected in a sterile plastic tube over a period of 5 min while the subject chewed on paraffin wax, and were then immediately stored at –80°C until use. Template DNA was obtained from the stored saliva using an Easy-DNA Kit (Invitrogen, CA, USA) according to the manufacturer's instructions. Conventional PCR assays were used to confirm the presence of P . gingivalis . A 5' nuclease TaqMan PCR was used to quantify P . gingivalis in saliva. The relative numbers of bacteria were measured using the comparative threshold cycle method.
Results  We found a quantitative relationship between the P . gingivalis levels in saliva and the condition of halitosis in mouth air.
Conclusion  We analyzed the relationship between the relative amount of P . gingivalis in saliva and oral malodor.     

Changes in CSF neurotransmitters in infantile spasms

Cerebrospinal fluid (CSF) from 7 patients with infantile spasms (mean age: 6.7 months) was collected before and after treatment with adrenocorticotropic hormone (ACTH). The concentration of neurotransmitter metabolites was analyzed using high-performance liquid chromatography and compared to the metabolite concentration in the CSF from 7 age-matched controls (mean age: 6.1 months). Pretreatment levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid, 3-methoxy-4-hydroxyphenyl glycol (MHPG), and kynurenine were significantly lower in infantile spasm patients compared to controls. Following treatment, marked increases in 5-HIAA and decreases in kynurenine levels were observed in the CSF of the 5 infants whose seizures were eliminated or reduced by ACTH. In the 2 nonresponders 5-HIAA levels decreased. The level of MHPG was reduced slightly in 5 infants, including the 2 nonresponders, and was increased in 2 responders. CSF homovanillic acid levels increased in 4 infantile spasm infants and decreased in 3 following ACTH. These data demonstrate that the presence of seizures in infantile spasms is associated with a significant decrease in serotonergic activity and that elimination of seizures by ACTH is accompanied by increased serotonin turnover. The simultaneous increase of 5-HIAA and decrease of kynurenine, an alternate metabolite of tryptophan, suggests an underlying disturbance of tryptophan metabolism in infantile spasms. The possibility that elimination of seizures by ACTH may be related to decreased production of certain kynurenine metabolites, particularly quinolinic acid, is discussed.     

Testicular cancer with tumor thrombus extending to the inferior vena cava successfully removed using veno-venous bypass: A case report

A 33-year-old man with a left testicular tumor was referred to Shinshu University Hospital for advanced therapy. Radiographic imaging revealed multiple metastases in the retroperitoneal lymph nodes (RPLN) and bilateral lungs, as well as tumor thrombus that extended from the left renal vein to the inferior vena cava (IVC) adjacent to the right atrium. After orchidectomy, a diagnosis of embryonal carcinoma was made with a clinical stage of T1N2M1bS3, which has a poor prognosis, based on the International Germ Cell Cancer Collaborative Group consensus. After eight courses of chemotherapy, the patient's tumor markers normalized and the lung metastases disappeared, but the RPLN and tumor thrombus remained. Retroperitoneal lymph node dissection and thrombectomy were performed using a veno-venous bypass (VVB). The pathological examination of the thrombus revealed a mature teratoma. The patient has been disease-free since surgery.