Surgical strategy for medication-related osteonecrosis of the jaw (MRONJ) on maxilla: A multicenter retrospective study.

BACKGROUND/PURPOSE: Because the anatomy and the nature of the bone tissue between the mandible and maxilla are largely different, more site-specific studies are required to improve the healing rate on medication-related osteonecrosis of the jaw (MRONJ). The present study assessed maxillary MRONJ that was treated by surgery to understand its clinical characteristics, and to identify critical factors that influenced outcomes. MATERIALS AND METHODS: The medical records of 54 patients with maxillary MRONJ who underwent surgery were retrospectively reviewed. Variables related to the prognosis of MRONJ were extracted from the medical records and imaging, and were statistically analyzed. We also evaluated the concomitant maxillary sinusitis (MS) after the surgical treatment of MRONJ, based on CT evaluation and change of symptoms. RESULTS: The healing rate of surgery for maxillary MRONJ was 85.2%, which suggested that surgical treatment is an effective strategy for treating maxillary MRONJ. Multivariate analysis revealed that postoperative residual necrotic bone was a poor prognosticator for maxillary MRONJ. Among 10 patients who did not obtain healing of MS postoperatively, 8 patients showed an improvement. CONCLUSION: Our results indicate that surgical treatment is an appropriate strategy for maxillary MRONJ and complete resection of necrotic bone (i.e., extensive surgery) is needed to obtain complete healing of maxillary MRONJ. Concomitant MS tends to be healed or improved clinically in combination with the healing of maxillary MRONJ.

Efficacy of silicone soft reliner on the obturator prosthesis after maxillectomy for oral malignant tumors: A single-arm prospective interventional study.

BACKGROUND: There is insufficient evidence for the efficacy of silicone soft reliner on the obturator prosthesis after maxillectomy for oral malignant tumors. OBJECTIVE: To verify the efficacy of silicone soft reliner on the obturator prosthesis after maxillectomy, by evaluating masticatory performance and quality of life (QoL). METHODS: This was a single-arm prospective interventional study, verifying the efficacy of silicone soft reliner (GC RELINE II®) on the maxillary obturator prosthesis. Data were obtained from a comparison of the endpoints after 14 days of continuous use of acrylic and silicone soft-lined prostheses. The primary endpoint was masticatory performance. The secondary endpoints were occlusal performance and oral health-related QoL (OHRQoL). The masticatory performance, occlusal performance, and OHRQoL were assessed by glucose concentration, maximum bite force, and the Japanese version of Oral Health Impact Profile (OHIP-J49), respectively. RESULTS: This study included five patients (two males, three females), aged between 71 and 88 years, with a median of 74 years. The median of glucose concentration indicated a statistically significant improvement between the acrylic resin (99.6 mg/dL) and silicone soft reliner (126.0 mg/dL) obturator prosthesis (p = .043). There was no significant difference in the median of maximum bite force between the acrylic resin (302.0 N) and silicone soft reliner (250.0 N) obturator prosthesis (p = .893). Functional limitations domain of the OHIP-J49 indicated a statistically significant improvement between the acrylic resin and silicone soft reliner obturator prosthesis (p = .043). CONCLUSIONS: This study indicated that an obturator relined with soft silicone improved masticatory performance and the OHRQoL post-maxillectomy.

Treatment outcomes of adjunctive teriparatide therapy for medication-related osteonecrosis of the jaw (MRONJ): A multicenter retrospective analysis in Japan.

BACKGROUND: Therapeutic strategies for patients with medication-related osteonecrosis of the jaw (MRONJ) remain controversial. The aim of the present study was to clarify the effectiveness and safety of teriparatide therapy in Japanese MRONJ patients based on a large number of case series with a multicenter retrospective analysis. PATIENTS AND METHODS: Between January 2012 and December 2016, 29 patients who were diagnosed with MRONJ at 10 hospitals were treated with teriparatide. The medical records of these patients were retrospectively reviewed to assess the efficacy and safety of teriparatide therapy for MRONJ patients. RESULTS: Adverse events occurred in 17.2% of patients (5/29). One patient developed severe arthralgia and discontinued teriparatide therapy after 12 days, while others continued the treatment. Among 29 patients, the median period of administration of teriparatide was 14.0 months (range, 0.3-26 months), and treatment outcomes were evaluated as effective in 75.9% of patients with complete resolution in 65.5%. Among patients treated with oral bisphosphonates (BPs), 83.3% were effectively treated with teriparatide and 40% with intravenous BPs. The oral administration of BPs was associated with successful treatment outcomes with teriparatide (p = 0.062). CONCLUSIONS: Teriparatide therapy has potential as an effective treatment option for MRONJ.

Factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas: a retrospective multicenter study of 326 patients.

PURPOSE: The present retrospective multicenter study intended to investigate the factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas. METHODS: A total of 326 patients who underwent radiotherapy for oral and oropharyngeal cancers were enrolled in the study. The patients' age, sex, body mass index, primary site, diabetes, serum albumin, creatinine, hemoglobin, leukocyte and lymphocyte, concurrent cisplatin or cetuximab, method of radiation, total radiation dose, feeding route, use of spacers, pilocarpine hydrochloride, and corticosteroid ointment were examined, and the associations of each variable with oral mucositis and candidiasis were analyzed by multivariate Cox regression analysis. RESULTS: Grade 3 oral mucositis occurred in 136 (41.7%) patients. Male sex, oropharyngeal cancer, low hemoglobin levels, low leukocytes or lymphocytes, concurrent cisplatin or cetuximab, and oral feeding were found to be significantly associated with a higher incidence of severe oral mucositis. Oral candidiasis occurred in 101 (31.0%) patients. Oropharyngeal cancer, low leukocyte count, and oral mucositis of grade 2 or higher were found to be significantly associated with a higher incidence of oral candidiasis. The use of a topical steroid ointment was not found to be a risk factor for oral candidiasis. CONCLUSIONS: The present retrospective study demonstrated that certain factors may predispose patients with oral and oropharyngeal cancers receiving radiotherapy to develop severe oral mucositis and oral candidiasis. A preventive strategy for severe oral mucositis needs to be established in the future for high-risk cases.

Clinical significance of periosteal reaction as a predictive factor for treatment outcome of medication-related osteonecrosis of the jaw.

Regarding treatment strategies for medication-related osteonecrosis of the jaw (MRONJ), surgical therapy has recently been reported to be more effective than conservative therapy. However, some patients did not achieve complete healing, even when extensive surgery was performed. Periosteal reaction in MRONJ patients is often observed by the CT examination. Tssshe purpose of this study was to investigate the relationship between periosteal reaction and treatment outcome of MRONJ. A total of 164 surgeries in 136 patients with MRONJ at two hospitals were included in the study. Correlations between various clinical and radiographic factors and treatment outcome were examined with Cox regression analysis. The results showed that the presence of periosteal reaction, as well as primary disease involving malignant tumor, were independent risk factors related to poor outcome. Furthermore, we examined factors related to the occurrence of the periosteal reaction and found that 4 variables were significantly correlated with periosteal reaction by multivariate analysis: gender (female), site (lower jaw), primary disease (malignant tumor), and osteosclerosis (severe). The present study clarified that the cure rate after surgical treatment decreased in cases with periosteal reaction, suggesting that it is necessary to review the treatment method.

Effect of perioperative oral management on the prevention of surgical site infection after colorectal cancer surgery: A multicenter retrospective analysis of 698 patients via analysis of covariance using propensity score.

Surgical site infection (SSI) is 1 of the frequent postoperative complications after colorectal cancer surgery. Oral health care has been reported to reduce the risk of SSI or postoperative pneumonia in oral, esophageal, and lung cancer surgeries. The purpose of the study was to investigate the preventive effect of perioperative oral management on the development of SSI after a major colorectal cancer surgery.The medical records of 698 patients who underwent colorectal cancer surgery at 2 hospitals in Japan were reviewed. Among these patients, 563 patients received perioperative oral management (oral management group) and 135 did not (control group). Various demographic, cancer-related, and treatment-related variables including perioperative oral management intervention and the occurrence of SSI were investigated. The relationship between each variable and the occurrence of SSI was examined via univariate and multivariate analyses using Fisher exact test, 1-way analysis of variance (ANOVA), and logistic regression. The occurrence of SSI in the 2 groups was evaluated via logistic regression using propensity score as a covariate. The difference in mean postoperative hospital stay between the oral management and control groups was analyzed using Student's t test.SSI occurred in 68 (9.7%) of the 698 patients. Multivariate analysis showed that operation time, blood loss, and perioperative oral management were significantly correlated with the development of SSI. However, after the propensity score analysis, not receiving perioperative oral management also became a significant risk factor for SSI. The odds ratio of the oral management group was 0.484 (P = .014; 95% confidence interval: 0.272-0.862). Mean postoperative hospital stay was significantly shorter in the oral management group than in the control group.Perioperative oral management reduces the risk of SSI after colorectal cancer surgery and shortens postoperative hospital stay.

Unusual recurrent tongue spindle cell carcinoma with marked anaplasia occurring at the site of glossectomy for a well-differentiated squamous cell carcinoma: A case report.

Spindle cell carcinoma (SpCC), which predominantly arises in the oral, pharyngeal and laryngeal mucosal tissues, is composed of a mixture of squamous and sarcomatoid components. The present study describes the case of a 62-year-old woman with SpCC recurrence 4 years after an initial surgery to remove a well-differentiated primary squamous cell carcinoma (SCC) of the tongue. The recurrent tumor was spherical and located deep within the tongue tissue, which differs from the typical manifestation of ulcerated masses of the mucosa. The majority of cases of recurrence involving SpCC are associated with radiotherapeutic treatment of the primary malignancy; however, the patient in the present study had not received postoperative radiotherapy for SCC. Furthermore, the recurrent tumor in the present case exhibited marked anaplasia and sarcomatoid features, and the absence of SCC elements upon biopsy rendered histological diagnosis difficult. In summary, the present findings suggest that immunohistochemical examination and identification of SCC components are essential for ensuring the accuracy of the histological diagnosis of recurrent SpCC following a primary epithelial malignancy.

Intraoral extraction of an ectopic mandibular third molar detected in the subcondylar region without a pathological cause: A case report and literature review.

PURPOSE: To present a case report on the presence of an ectopic mandibular third molar (EMTM), the surgical treatment, and outcome. CASE REPORT: A 63-year-old woman presented with right preauricular facial swelling, limited jaw function, and pain. Radiographic assessment demonstrated an EMTM positioned in the superoposterior aspect of the ramus. Radiographically, there was a bony tunnel extending from the third molar to distal of the second molar. The patient was treated by an intraoral approach on the medial aspect of the ramus for removal of the ectopic third molar, as well as the tissue in the bony tunnel. RESULTS: The patient healed uneventfully. The soft tissue in the bony canal was granulation tissue, and nerve function was preserved. A literature search of EMTMs was conducted identifying 17 reported cases. CONCLUSION: Three-dimensional imaging in the management of EMTM can be beneficial in identifying position of the tooth, associated pathology, and identifying the position of neurovascular structures to aid in removal of the ectopic tooth.

Clinical Roles of Interleukin-6 and STAT3 in Oral Squamous Cell Carcinoma.

The effect inflammation has on cancer prognosis is marked by the presence of cytokines and chemokines. Interleukin-6 (IL-6) is one a multifunctional cytokine that regulates inflammatory responses. We investigated the roles of IL-6 and STAT3 and examined the relationship between IL-6 signaling and clinicopathological factors in patients with oral squamous cell carcinoma (OSCC). We retrospectively examined 116 patients who underwent radical surgery for OSCC. IL-6 and STAT3 expression were detected by immunohistochemistry. IL-6 and STAT3 positivity were detected by IHC, at 78.4 and 80.2 %, respectively. IL-6 expression was significantly associated with pattern of invasion (P = 0.004), vascular invasion (P = 0.003), and pathological nodal status (P = 0.019). Multivariate logistic regression analysis revealed that IL-6 expression was significantly associated with vascular invasion (P = 0.044). Meanwhile, there was no significant association between STAT3 expression and clinicopathological factors and no significant relationship between IL-6 and STAT3 expression. IL-6 expression was significantly associated with 5-year disease-free survival. These results suggest that IL-6 is involved in lymphangiogenesis and recurrence in OSCC.

Alternaria extract activates autophagy that induces IL-18 release from airway epithelial cells.

Alternaria alternata is a major outdoor allergen that causes allergic airway diseases. Alternaria extract (ALT-E) has been shown to induce airway epithelial cells to release IL-18 and thereby initiate Th2-type responses. We investigated the underlying mechanisms involved in IL-18 release from ALT-E-stimulated airway epithelial cells. Normal human bronchial epithelial cells and A549 human lung adenocarcinoma cells were stimulated with ALT-E in the presence of different inhibitors of autophagy or caspases. IL-18 levels in culture supernatants were measured by ELISA. The numbers of autophagosomes, an LC3-I to LC3-II conversion, and p62 degradation were determined by immunofluorescence staining and immunoblotting. 3-methyladenine and bafilomycin, which inhibit the formation of preautophagosomal structures and autolysosomes, respectively, suppressed ALT-E-induced IL-18 release by cells, whereas caspase 1 and 8 inhibitors did not. ALT-E-stimulation increased autophagosome formation, LC-3 conversion, and p62 degradation in airway epithelial cells. LPS-stimulation induced the LC3 conversion in A549 cells, but did not induce IL-18 release or p62 degradation. Unlike LPS, ALT-E induced airway epithelial cells to release IL-18 via an autophagy dependent, caspase 1 and 8 independent pathway. Although autophagy has been shown to negatively regulate canonical inflammasome activity in TLR-stimulated macrophages, our data indicates that this process is an unconventional mechanism of IL-18 secretion by airway epithelial cells.

Anti-tumor effect of the mammalian target of rapamycin inhibitor everolimus in oral squamous cell carcinoma.

The mammalian target of rapamycin (mTOR) has recently emerged as a promising target for therapeutic anti-cancer interventions in several human tumors. In present study, we investigated the expression of mTOR, and subsequently examined its relationship with clinicopathological factors and the anti-tumor effect of everolimus (also known as RAD001) in oral squamous cell carcinoma (OSCC). The expression of phosphorylated mTOR (p-mTOR) was immunohistochemically evaluated in specimens obtained from 70 OSCC patients who underwent radical surgery. The relationships between the expression of p-mTOR and clinicopathological factors and survival were determined. We also investigated the effect of everolimus on the OSCC cell lines, SAS, HSC-2, HSC-3, HSC-4, OSC-20, SCC25 and Ca9-22 by the MTT assay. We further evaluated whether mTOR contributed to cell functions by blocking its activity with everolimus, and confirmed the direct target by the Matrigel invasion assay, wound healing assay and Western blotting. p-mTOR was overexpressed in 37 tumors (52.8 %), and correlated with the T classification, N classification, and survival rate (P < 0.05). The treatment with everolimus significantly inhibited cell growth, and significantly reduced the expression of p-mTOR, downstream signaling proteins, and hypoxic related proteins as well as invasion and migration potentials (P < 0.05). The results of the present study suggest that everolimus may represent an attractive approach for the future treatment of OSCC.

Lipomas of the oral cavity: clinicopathological and immunohistochemical study of 24 cases and review of the literature.

Although lipomas are common soft tissue tumors, few cases of lipoma or its variants have been reported in the oral cavity. We here described the clinical, histological, and immunohistochemical features of 24 cases of oral lipoma obtained from medical records at Nagasaki University Hospital between 1977 and 2010, and also retrospectively reviewed 603 cases of oral lipoma reported in the English literatures. The patients examined comprised 11 men and 13 women with a mean age of 59 years, ranging from 31 to 90 years. The main sites involved were the buccal mucosa (n = 9), followed by the tongue (n = 4), lip and retromolar area (n = 3), floor of the mouth (n = 2), and gingiva (n = 1). The mean tumor size was 2.0 cm, ranging from 0.2 to 5 cm. Histological analysis revealed 20 cases of lipoma, 2 cases of fibrolipoma, and one case each of intramuscular lipoma and spindle cell lipoma. Twenty-three cases were treated surgically while one case underwent biopsy and follow-up. Recurrence was not observed in any case. We reviewed the English literatures, and similar results were obtained. In immunohistochemical analysis, PCNA and ki-67 expression indices were higher in intramuscular lipoma cases than in its variants. Especially, it showed that a long time follow-up may be necessary in ki-67 positive cases.

IL-33 enhanced the proliferation and constitutive production of IL-13 and IL-5 by fibrocytes.

Interleukin-33 appears to play important roles in the induction of allergic airway inflammation. However, whether IL-33 is involved in airway remodeling remains unclear. Because fibrocytes contribute to tissue remodeling in the setting of chronic inflammation, we examined the effects of IL-33 on fibrocyte functions. Fibrocytes were generated in vitro from peripheral blood mononuclear cells by culturing in the presence of platelet derived growth factors and the cells were stimulated with IL-33. IL-33 enhanced cell proliferation, α-SMA expression, and pro-MMP-9 activity by the fibrocytes without increasing endogenous transforming growth factor-ß1 production. Fibrocytes constitutively expressed IL-13 and IL-5, and their production was augmented by stimulation with IL-33. Dexamethasone inhibited the functions of fibrocytes, but IL-33 made fibrocytes slightly refractory to the inhibitory effect of dexamethasone in terms of IL-13 production. Montelukast suppressed IL-13 production by nonstimulated fibrocytes but not those stimulated by IL-33. These findings suggest that IL-33 is involved in the airway remodeling process through its modulation of fibrocyte function independent of antigen stimulation. IL-33 might partially reduce the therapeutic effects of glucocorticoid and cysteinyl leukotriene receptor antagonist on fibrocyte-mediated Th2 responses.

Rice protein-induced enterocolitis syndrome with transient specific IgE to boiled rice but not to retort-processed rice.

Described herein is the case of an 8-month-old girl with atypical food protein-induced enterocolitis syndrome due to rice. She presented with vomiting and poor general activity 2 h after ingestion of boiled rice. Oral food challenge test using high-pressure retort-processed rice was negative, but re-exposure to boiled rice elicited gastrointestinal symptoms. On western blot analysis the patient's serum was found to contain IgE bound to crude protein extracts from rice seed or boiled rice, but not from retort-processed rice. The major protein bands were not detected in the electrophoresed gel of retort-processed rice extracts, suggesting decomposition by high-temperature and high-pressure processing. Oral food challenge for diagnosing rice allergy should be performed with boiled rice to avoid a false negative. Additionally, some patients with rice allergy might be able to ingest retort-processed rice as a substitute for boiled rice.

MicroRNA-21 promotes oral cancer invasion via the Wnt/ß-catenin pathway by targeting DKK2.

MicroRNA-21 (miR-21) is overexpressed in a wide variety of cancers and has been related to cellular proliferation, apoptosis, and invasion; however, the function of miR-21 is unknown in oral tongue squamous cell carcinoma (OTSCC). The purpose of this study was to examine miR-21 expression in OTSCC, correlate it with clinicopathological factors, and investigate its contribution to OTSCC cell invasion. MiR-21 expression in 79 primary OTSCCs was evaluated using locked nucleic acid in situ hybridization, and correlation was examined with the clinicopathological factors. To determine the miR-21 target, we searched for molecular genes involved in tumor invasion using the commonly cited prediction program miRanda. In an OTSCC cell line, SCC25 cells, we further evaluated whether miR-21 contributes to cell invasiveness by blocking its expression with a specific knockdown LNA probe and confirmed the direct target by Matrigel invasion assay and Western blotting. MiR-21 overexpression was detected in 60 of 79 cases (75.9 %) and correlated with the pattern of invasion (P = 0.016). We selected DKK2 as a Wnt/antagonist involved in tumor invasion. MiR-21 overexpression was significantly correlated with the DKK2-/ß-catenin- immunohistochemical phenotype. Knockdown of miR-21 significantly decreased the invasion potential of SCC25 cells with up-regulated DKK2. It was found that miR-21 is overexpressed and associated with tumor invasion in OTSCC, and that miR-21 promotes OTSCC cell invasion via the Wnt/ß-catenin pathway by targeting DKK2 in vitro. These results suggest that miR-21 may be a potential therapeutic target for OTSCC treatment.

A nationwide survey of Aicardi-Goutières syndrome patients identifies a strong association between dominant TREX1 mutations and chilblain lesions: Japanese cohort study.

OBJECTIVES: Aicardi-Goutières syndrome (AGS) is a rare, genetically determined, early onset progressive encephalopathy associated with autoimmune manifestations. AGS is usually inherited in an autosomal recessive manner. The disease is rare, therefore the clinical manifestations and genotype-phenotype correlations, particularly with regard to autoimmune diseases, are still unclear. Here we performed a nationwide survey of AGS patients in Japan and analysed the genetic and clinical data. METHODS: Patients were recruited via questionnaires sent to paediatric or adult neurologists in Japanese hospitals and institutions. Genetic analysis was performed and clinical data were collected. RESULTS: Fourteen AGS patients were identified from 13 families; 10 harboured genetic mutations. Three patients harboured dominant-type TREX1 mutations. These included two de novo cases: one caused by a novel heterozygous p.His195Tyr mutation and the other by a novel somatic mosaicism resulting in a p.Asp200Asn mutation. Chilblain lesions were observed in all patients harbouring dominant-type TREX1 mutations. All three patients harbouring SAMHD1 mutations were diagnosed with autoimmune diseases, two with SLE and one with SS. The latter is the first reported case. CONCLUSION: This study is the first to report a nationwide AGS survey, which identified more patients with sporadic AGS carrying de novo dominant-type TREX1 mutations than expected. There was a strong association between the dominant-type TREX1 mutations and chilblain lesions, and between SAMHD1 mutations and autoimmunity. These findings suggest that rheumatologists should pay attention to possible sporadic AGS cases presenting with neurological disorders and autoimmune manifestations.

[Case of atopic dermatitis in infant treated with Chinese herbal medicines and nsaids ointment, which induced weight loss, electrolyte disturbance and hypoproteinemia].

We report here a 4-month-old girl with atopic dermatitis accompanied by weight loss, electrolyte disturbance, hypoproteinemia and hypogammaglobulinemia. She has suffered from eczema since one-month of age. Although she was treated with Chinese herbal medicines, including Syosaikotokakikyosekko, Tokishigyakukagoshuyushokyoto and Jumihaidokuto and ibuprofen ointment since three-month of age, she was referred to our hospital due to deteriorated eczema, severe diarrhea and failure to thrive. Laboratory examination revealed hyponatremia, hyperpotassemia, hypoproteinemia, hypogammaglobulinemia and elevated levels of serum IL-18, TARC and fecal EDN. Drug-induced lymphocyte stimulation tests were positive for the prescribed Chinese herbal medicines. Discontinuation of these medicines and application of steroid ointments improved loose bowels and skin lesions as well as laboratory data. It is suggested that the application of inadequate ointment and Chinese herbal medicines exaggerated inflammation in the skin and the intestinal mucosa leading to electrolyte disturbance, hypoproteinemia and hypogammaglobulinemia. Chinese herbal medicines are depicted as an additional therapy in Japanese guideline for atopic dermatitis, whereas their indication to infants with atopic dermatitis should be carefully assessed.

Paroxysmal cold hemoglobinuria caused by an IgM-class Donath-Landsteiner antibody.

We report on a 4-year-old boy who developed paroxysmal cold hemoglobinuria (PCH) following the first dose of a seven-valent pneumococcal conjugate vaccine. He was admitted because of dark urine after exposure to cold air. Laboratory tests indicated anemia, increased serum indirect bilirubin and lactate dehydrogenase, and decreased serum haptoglobin. Donath-Landsteiner (D-L) test was positive. The D-L antibody belonged to the IgM class and exhibited anti-P specificity. Symptoms and signs subsided after supportive care without any medication. Although PCH is often associated with viral or bacterial infection and is caused by IgG-class D-L antibodies with anti-P specificity, this case was unique because a D-L antibody of the IgM class with anti-P specificity caused PCH after immunization with a pneumococcal vaccine.

IL-17A/F modulates fibrocyte functions in cooperation with CD40-mediated signaling.

T helper 17 (Th17) cells that produce interleukin (IL)-17A and IL-17F have been found to participate in the development of bronchial asthma and bleomycin-induced pulmonary fibrosis. However, whether they play a causative role in the airway remodeling observed in these respiratory diseases remains unclear. Because fibrocytes are involved in tissue repair and fibrosis and are presumably precursors of lung fibroblasts and myofibroblasts, we examined the effects of IL-17A/F on fibrocyte functions. Both IL-17A and IL-17F enhanced fibrocytes' α-smooth muscle actin expression. Priming fibrocytes with IL-17A enhanced their CD40-mediated IL-6 production, whereas IL-17F-priming increased the CD40-mediated mRNA expression of collagen I, vascular endothelial growth factor, and angiogenin. CD4(+) T cells co-cultured with fibrocytes produced IL-17A, which was inhibited by blocking CD40 and CD40 ligand interactions. These findings suggest that cooperative interactions between fibrocytes and Th17 cells play an important role via CD40- and IL-17A/F-mediated signaling for collagen and proangiogenic factor production, which may lead to the extracellular matrix deposition and neovascularization seen in airway remodeling.

Biotin and carnitine profiles in preterm infants in Japan.

BACKGROUND: Biotin plays an important role as a covalently bound coenzyme for carboxylases. Carnitine is essential in ß-oxidation to transport long-chain fatty acids across the inner mitochondrial membrane. The present study was conducted to assess the risk of biotin and carnitine deficiencies in preterm infants who received enteral feeding with maternal milk and/or standard infant formula made in Japan. METHODS: Forty-six infants were enrolled in the study. Urine and serum samples and dried blood spots were collected at 1 week and 1 month of age. Additionally, samples were collected at 40 and 44 weeks post-menstrual age (PMA) in preterm infants. Free carnitine and C5-OH acylcarnitine, which consist of 3-hydroxyisovalerylcarnitine as a major isomer, were measured in serum samples and dried blood spots using tandem mass spectrometry. Urine 3-hydroxyisovaleric acid (3-HIVA) was measured using gas chromatography/mass spectrometry. RESULTS: The free carnitine levels in preterm infants were significantly lower than those in term infants, but increased with PMA in serum samples and dried blood spots. C5-OH acylcarnitine and urinary 3-HIVA levels, which were very low in term infants, were increased with PMA in preterm infants. CONCLUSION: The present results may indicate chronic biotin deficiency in preterm infants fed maternal milk and/or standard infant formula. Analyses of carnitine profiles of dried blood spots and urine 3-HIVA are relatively non-invasive and useful for the early detection of biotin deficiency in preterm infants.