Osterix (Osx) is essential for osteoblast differentiation and bone formation, because mice lacking Osx die within 1 h of birth with a complete absence of intramembranous and endochondral bone formation. Perinatal lethality caused by the disruption of the Osx gene prevents studies of the role of Osx in bones that are growing or already formed. Here, the function of Osx was examined in adult bones using the time- and site-specific Cre/loxP system. Osx was inactivated in all osteoblasts by Col1a1-Cre with the activity of Cre recombinase under the control of the 2.3-kb collagen promoter. Even though no bone defects were observed in newborn mice, Osx inactivation with 2.3-kb Col1a1-Cre exhibited osteopenia phenotypes in growing mice. BMD and bone-forming rate were decreased in lumbar vertebra, and the cortical bone of the long bones was thinner and more porous with reduced bone length. The trabecular bones were increased, but they were immature or premature. The expression of early marker genes for osteoblast differentiation such as Runx2, osteopontin, and alkaline phosphatase was markedly increased, but the late marker gene, osteocalcin, was decreased. However, no functional defects were found in osteoclasts. In summary, Osx inactivation in growing bones delayed osteoblast maturation, causing an accumulation of immature osteoblasts and reducing osteoblast function for bone formation, without apparent defects in bone resorption. These findings suggest a significant role of Osx in positively regulating osteoblast differentiation and bone formation in adult bone.
Osterix; Col1a1-Cre; osteopenia; osteoblast differentiation; adult bone formation
Impairment of cognitive function is often present in patients with carotid artery stenosis but the details of this dysfunction have rarely been reported. Our purpose was to elucidate the cognitive dysfunction in patients with unilateral severe carotid stenosis using comprehensive neuropsychological testing, and also to identify the specific underlying clinical and radiological factors.
We analyzed the results of neuropsychological testing, the clinical history, and MR findings in 16 consecutive patients with angiographically proven severe (70-99%) stenosis of the extra cranial internal carotid artery (ICA). Cognitive functions were examined using the Seoul Neuropsychological Screening Battery and the Neglect Battery. We excluded patients with cortical infarction and those with contra lateral ICA occlusion or severe stenosis.
Our comprehensive neuropsychological testing revealed obvious cognitive deficits in all patients with unilateral severe ICA stenosis, the most common being frontal executive impairment. The mean cognitive score on the memory test was also significantly lower in patients with symptomatic ICA stenosis than in asymptomatic patients (29.33±10.98, mean±SD, p < 0.05). The total score on the global cognitive test was significantly lower in patients with an ischemic lesion on MRI than in no lesion patients (113.23±34.78, p < 0.05). The presence of symptoms related to the ICA stenosis was related to cognitive dysfunction even when there were no ischemic lesions on MRI. SPECT revealed ipsilateral cortical hypoperfusion in 9 of 12 patients (75%).
Cognitive deficits are common in patients with unilateral severe ICA stenosis. Our findings suggest that an additional mechanism beyond the structural lesion such as chronic hypoperfusion may affect cognitive function in patients with high-grade ICA stenosis.
Minor stroke; ICA stenosis; Neuropsychological test; Chronic hypoperfusion
We report unusual MRI findings (including those from diffusion-weighted imaging (DWI)) in a patient with recurrent Wernicke's encephalopathy with a remarkable cerebellar lesion. DWI showed high signal intensities in the superior portion of the cerebellar hemisphere and vermis area. After thiamine administration, clinical symptoms improved and the lesions with high signal intensities disappeared on follow-up DWI.
Recurrent Wernicke's encephalopathy; Cerebellum; MRI; DWI
Patients with atopic dermatitis (AD) should be relatively well informed about the disorder to control their condition and prevent flare-ups. Thus far, there is no accurate information about the disease awareness levels and therapeutic behavior of AD patients.
To collect data on patients' knowledge about AD and their behavior in relation to seeking information about the disease and its treatment.
We performed a questionnaire survey on the disease awareness and self-management behavior of AD patients. A total of 313 patients and parents of patients with AD who had visited the The Catholic University of Korea, Catholic Medical Center between November 2011 and October 2012 were recruited. We compared the percentage of correct answers from all collected questionnaires according to the demographic and disease characteristics of the patients.
Although dermatologists were the most frequent disease information sources and treatment providers for the AD patients, a significant proportion of participants obtained information from the Internet, which carries a huge amount of false medical information. A considerable number of participants perceived false online information as genuine, especially concerning complementary and alternative medicine treatments of AD, and the adverse effects of steroids. Some questions on AD knowledge had significantly different answers according to sex, marriage status, educational level, type of residence and living area, disease duration, disease severity, and treatment history with dermatologists.
Dermatologists should pay more attention to correcting the common misunderstandings about AD to reduce unnecessary social/economic losses and improve treatment compliance.
Awareness; Complementary therapies; Dermatitis; atopic; Disease management; Information seeking behavior
The aim of the present study is to establish a bacterial clone capable of secreting an integrin αvβ3 targeting probe with bioluminescent and fluorescent activities, and to verify its specific targeting and optical activities using molecular imaging. A bacterial vector expressing a fusion of secretory Gaussia luciferase (sGluc), mCherry, and RGD (sGluc-mCherry-RGDX3; GCR), and a control vector expressing a fusion of secretory Gaussia luciferase and mCherry (sGluc-mCherry; GC) were constructed. The GCR and GC proteins were expressed in E. coli and secreted into the growth medium, which showed an approximately 10-fold higher luciferase activity than the bacterial lysate. Successful purification of GCR and GC was achieved using the 6X His-tag method. The GCR protein bound with higher affinity to U87MG cells than CHO cells in confocal microscopy and IVIS imaging, and also showed a high affinity for integrin αvβ3 expressing tumor xenografts in an in vivo animal model. An E. coli clone was established to secrete an integrin αvβ3 targeting imaging probe with bioluminescent and fluorescent activities. The probe was produced feasibly and at low cost, and has shown to be useful for the assessment of angiogenesis in vitro and in vivo.
Silicon dioxide (SiO2) and zinc oxide (ZnO) nanoparticles are widely used in various applications, raising issues regarding the possible adverse effects of these metal oxide nanoparticles on human cells. In this study, we determined the cytotoxic effects of differently charged SiO2 and ZnO nanoparticles, with mean sizes of either 100 or 20 nm, on the U373MG human glioblastoma cell line. The overall cytotoxicity of ZnO nanoparticles against U373MG cells was significantly higher than that of SiO2 nanoparticles. Neither the size nor the surface charge of the ZnO nanoparticles affected their cytotoxicity against U373MG cells. The 20 nm SiO2 nanoparticles were more toxic than the 100 nm nanoparticles against U373MG cells, but the surface charge had little or no effect on their cytotoxicity. Both SiO2 and ZnO nanoparticles activated caspase-3 and induced DNA fragmentation in U373MG cells, suggesting the induction of apoptosis. Thus, SiO2 and ZnO nanoparticles appear to exert cytotoxic effects against U373MG cells, possibly via apoptosis.
The primary care system in the Republic of Korea has weakened over the past decade and is now in poorer condition than the systems in other countries. However, little is known about how the two key players, patients and physicians, view the current status of primary care in Korea. This study aims to understand what problems they perceive in respect to the key components of primary care.
We conducted two focus groups; one with six patients and the other with six physicians. We designed and modified the guidelines for each focus group discussion through repeated review and discussion among all authors and then we conducted the groups with a professional interviewer at Gallup Korea. After the focus groups we analyzed the verbatim transcriptions to identify specific meanings and potential implications.
From the study we identified that the patients and physicians did not have a correct understanding about the role of primary care. We also identified a significant discrepancy between their perception of primary care. In particular, the patient group perceived the quality of primary care to be poor and unsatisfactory while the physician group perceived the quality of primary care to be better in Korea than in other countries.
The focus group discussions revealed that such discrepancies in perception have resulted from Korea’s distorted healthcare delivery system, undifferentiated roles among healthcare organizations, patients’ freedom of choice in selecting healthcare providers and other institutional factors. There are several steps that should be taken to promote primary care in Korea. First, we should undertake efforts to improve the quality of primary care provided by physicians. Second, we should inform the general public about using clinics instead of hospitals for the treatment of simple or minor diseases. Third, we should introduce a new compensation scheme to compensate physicians for services related to health education, disease prevention, behavioral change and nutrition consultation. Finally, we should provide additional reimbursement so that primary care physicians can extend their office hours to better meet the needs of patients.
Primary care; Focus group discussion; Quality of care
We have previously reported that interleukin-1 (IL-1) receptor-associated kinase (IRAK1) is essential for Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1)-induced p65/RelA serine 536 phosphorylation and NF-κB activation but not for IκB kinase α (IKKα) or IKKβ activation (Y. J. Song, K. Y. Jen, V. Soni, E. Kieff, and E. Cahir-McFarland, Proc. Natl. Acad. Sci. U. S. A. 103:2689–2694, 2006, doi:10.1073/pnas.0511096103). Since the kinase activity of IRAK1 is not required for LMP1-induced NF-κB activation, IRAK1 is proposed to function as a scaffold protein to recruit a p65/RelA serine 536 kinase(s) to enhance NF-κB-dependent transcriptional activity. We now report that Ca2+/calmodulin-dependent protein kinase II (CaMKII) interacts with IRAK1 and is critical for LMP1-induced p65/RelA serine 536 phosphorylation and NF-κB activation. CaMKII bound the death domain of IRAK1 and directly phosphorylated p65/RelA at serine 536 in vitro. Downregulation of CaMKII activity or expression significantly reduced LMP1-induced p65/RelA serine 536 phosphorylation and NF-κB activation. Furthermore, LMP1-induced CaMKII activation and p65/RelA serine 536 phosphorylation were significantly reduced in IRAK1 knockout (KO) mouse embryonic fibroblasts (MEFs). Thus, IRAK1 may recruit and activate CaMKII, which phosphorylates p65/RelA serine 536 to enhance the transactivation potential of NF-κB in LMP1-induced NF-κB activation pathway.
This study tested the effectiveness of moxibustion on pain and function in chronic knee osteoarthritis (KOA) and evaluated safety.
A multi-centre, non-blinded, parallel-group, randomised controlled trial compared moxibustion with usual care (UC) in KOA. 212 South Korean patients aged 40–70 were recruited from 2011–12, stratified by mild (Kellgren/Lawrence scale grades 0/1) and moderate-severe KOA (grades 2/3/4), and randomly allocated to moxibustion or UC for four weeks. Moxibustion involved burning mugwort devices over acupuncture and Ashi points in affected knee(s). UC was allowed. Korean Western Ontario and McMaster Universities Questionnaire (K-WOMAC), Short Form 36 Health Survey (SF-36v2), Beck Depression Inventory (BDI), physical performance test, pain numeric rating scale (NRS) and adverse events were evaluated at 5 and 13 weeks. K-WOMAC global score at 5 weeks was the primary outcome.
102 patients (73 mild, 29 moderate-severe) were allocated to moxibustion, 110 (77 mild, 33 moderate-severe) to UC. K-WOMAC global score (moxibustion 25.42+/−SD 19.26, UC 33.60+/−17.91, p<0.01, effect size = 0.0477), NRS (moxibustion 44.77+/−22.73, UC 56.23+/−17.71, p<0.01, effect size = 0.0073) and timed-stand test (moxibustion 24.79+/−9.76, UC 25.24+/−8.84, p = 0.0486, effect size = 0.0021) were improved by moxibustion at 5 weeks. The primary outcome improved for mild but not moderate-severe KOA. At 13 weeks, moxibustion significantly improved the K-WOMAC global score and NRS. Moxibustion improved SF-36 physical component summary (p = 0.0299), bodily pain (p = 0.0003), physical functioning (p = 0.0025) and social functioning (p = 0.0418) at 5 weeks, with no difference in mental component summary at 5 and 13 weeks. BDI showed no difference (p = 0.34) at 5 weeks. After 1158 moxibustion treatments, 121 adverse events included first (n = 6) and second degree (n = 113) burns, pruritus and fatigue (n = 2).
Moxibustion may improve pain, function and quality of life in KOA patients, but adverse events are common. Limitations included no sham control or blinding.
Clinical Research Information Service (CRIS) KCT0000130
A 28-year-old male patient with right maxillar, zygomatic arch, orbital wall, and nasal bone fractures had an orthognathic and nasal surgery. Naso-endotracheal intubation is the first choice during surgical correction of dentofacial deformities in an orthognathic surgery; however, its presence can interfere with concomitant surgical procedures on the nose. Traditionally, the naso-endotracheal tube will be removed and replaced with an oro-endotracheal tube. We changed the endotracheal tube from nasal to oral by using an airway exchange catheter.
Airway exchange catheter; Nasal surgery; Naso-endotracheal intubation; Orthognathic surgery
The effects of the Notch signaling pathway in fibroproliferative skin diseases have not been fully elucidated.
The aim of this study was to investigate the expression of activated Notch signaling molecules in various skin fibroproliferative diseases.
Immunohistochemical analysis of Notch intracellular domain (NICD) expression in keloid, hypertrophic scar, morphea, dermatofibroma, and normal control skin specimens was performed, and the clinical characteristics of patients with various skin fibroproliferative diseases were analyzed.
NICD was highly expressed in fibroblasts of keloids and moderately to highly expressed in hypertrophic scars and dermatofibromas, whereas low or no expression was detected in the fibroblasts of normal skin specimens and morpheas. NICD was constitutively expressed in keratinocytes, endothelial cells, and immune cells in normal skin specimens.
NICD was significantly expressed in human fibroproliferative skin disorders, especially keloids, suggesting that an activated Notch signaling pathway is involved in the pathogenesis of skin fibrosis.
Benign fibrous histiocytoma; Hypertrophic cicatrix; Keloid; Localized scleroderma; Notch receptors
Osterix (Osx) is a zinc-finger-containing transcription factor that is highly specific to osteoblasts in vivo. Because Osx homozygous null mutants die in the immediate perinatal period showing a complete absence of bone formation, it is impossible determine the role that Osx plays in bones that have already formed after birth. To determine whether Osx is essential for bone maintenance and homeostasis, we conditionally inactivated the Osx gene in adult bone using the Cre/loxP recombination system. In previous reports, 2.3-kb Col1a1-CreERT2 mice that expressed a Cre recombinase that is transiently inducible by 4-hydroxytamoxifen (4-OHT) were intercrossed with Rosa26R (R26R) reporter mice, which resulted in the production of Cre-expressing osteoblasts that were detected upon X-gal staining. In the present study, inducible Col1a1-CreERT2 transgenic mice and conditional Osx mice (Osxflox/+) were used to generate Osxflox/−; Col1a1-CreERT2 mice. The Osx gene in Osxflox/−; Col1a1-CreERT2 mice was inactivated in the osteoblasts of already formed bones by active Cre recombinase after the administration of 4-OHT. The bones from 4-OHT-treated Osxflox/−; Col1a1-CreERT2 mice and oil-treated control mice were analyzed by radiography, histology, and histomorphometry. Even though no significant difference was observed in the radiographic images of the whole mouse skeletons, the mineralized trabecular bone volume and number in lumbar vertebrae were remarkably reduced in 4-OHT-treated Osxflox/−; Col1a1-CreERT2 mice. In addition, the rate of bone formation and area of mineralized surface were also reduced in 4-OHT-treated Osxflox/−; Col1a1-CreERT2 mice. Osx inactivation in already formed bones during the postnatal period caused a functional defect in osteoblasts that was followed by a reduction of bone formation, even though there were no apparent differences in osteoblast proliferation and osteoclast formation. Taken together, these results indicate that Osx is required to maintain osteoblast function following adult bone maintenance.
Osterix; Col1a1-CreERT2; Postnatal; Osteoblasts; Bone maintenance
Osx plays essential roles in regulating osteoblast and chondrocyte differentiation, and bone formation during mouse skeletal development. However, many questions remain regarding the requirement for Osx in different cell lineages. In this study, we asked whether Osx is required for craniofacial bone formation derived from cranial neural crest (CNC) cells. The Osx gene was conditionally inactivated in CNC-derived cells using a Wnt1-Cre recombination system. Neural crest-specific inactivation of Osx resulted in the complete absence of intramembranous skeletal elements derived from the CNC, and CNC-derived endochondral skeletal elements were also affected by Osx inactivation. Interestingly, Osx inactivated CNC-derived cells, which were recapitulated by lacZ expression, occupied the same regions of craniofacial skeletal elements as observed for controls. However, cells lost their osteogenic ability to differentiate into functional osteoblasts by Osx inactivation. These results suggest that Osx is important for craniofacial bone formation by CNC-derived cells. This finding provides novel insights of the regulation of craniofacial development by the gene network and transcription factors, and the understanding of human diseases caused by neural crest developmental abnormalities.
Osterix; Wnt1-Cre; Cranial neural crest cells; Craniofacial
Osterix (Osx) is an essential transcription factor required for osteoblast differentiation during both intramembranous and endochondral ossification. Endochondral ossification, a process in which bone formation initiates from a cartilage intermediate, is crucial for skeletal development and growth. Osx is expressed in differentiating chondrocytes as well as osteoblasts during mouse development, but its role in chondrocytes has not been well studied. Here, the in vivo function of Osx in chondrocytes was examined in a chondrocyte-specific Osx conditional knockout model using Col2a1-Cre. Chondrocyte-specific Osx deficiency resulted in a weak and bent skeleton which was evident in newborn by radiographic analysis and skeletal preparation. To further understand the skeletal deformity of the chondrocyte-specific Osx conditional knockout, histological analysis was performed on developing long bones during embryogenesis. Hypertrophic chondrocytes were expanded, the formation of bone trabeculae and marrow cavities was remarkably delayed, and subsequent skeletal growth was reduced. The expression of several chondrocyte differentiation markers was reduced, indicating the impairment of chondrocyte differentiation and endochondral ossification in the chondrocyte-specific Osx conditional knockout. Taken together, Osx regulates chondrocyte differentiation and bone growth in growth plate chondrocytes, suggesting an autonomous function of Osx in chondrocytes during endochondral ossification.
Osterix; Col2a1-Cre; Chondrocytes; Endochondral ossification
This study reviewed clinical characteristics of fetal intra-abdominal umbilical vein (FIUV) varices that were detected during antenatal ultrasound examinations.
Between January 2006 and January 2012, 121 cases of FIUV varices were detected and 7 cases were lost to follow-up. We retrospectively reviewed the medical records of 114 patients and neonates.
From a total 96,553 ultrasound examinations in 43,995 pregnancies, 121 cases of FIUV varices were identified (2.8 per 1,000 pregnancies). Gestational age at diagnosis was 32.0 ± 2.9 weeks (range, 20.1-36.3 weeks), the mean diameter of the FIUV varix was 12.6 ± 2.1 mm (range, 8.0-21.0 mm) at initial diagnosis and the mean maximal diameter was 13.1 ± 2.3 mm (range, 8.0-21.0 mm) during follow-up. The most severe pregnancy complications included one case of intrauterine fetal death and another case of fetal hydrops. Associated fetal anomalies (n = 11, 9.6%) detected by ultrasonography included bilateral renal pelvis dilatation, ventriculomegaly, cryptorchidism, incomplete renal duplication and pulmonary sequestration. A total of 104 cases (91.2%) were delivered at term and 10 cases (8.8%) were preterm deliveries before 37 weeks of gestation.
FIUV varices that are not associated with fetal anomalies based on ultrasound examination during prenatal care have favorable pregnancy outcomes. Nevertheless, close fetal monitoring is recommended to decrease perinatal complications.
Antenatal ultrasound; Umbilical veins; Varicose veins
The Korean subclade of subtype B (KSB) is the most prevalent HIV-1 strain found in Korea. To date, only two near full-length HIV-1 sequences from Korean patients have been reported. Here, we analyzed a total of 24 near full-length genomes of HIV-1 strains that were isolated from 17 antiretroviral therapy (ART)-naive patients and four ART-exposed patients. Proviral DNA from peripheral blood mononuclear cells was PCR amplified and directly sequenced. Phylogenetic analyses were used to classify viruses from 19 patients as KSB, from one patient as subtype B, from one patient as subtype D, and three viruses from one patient as CRF02_AG. All KSB viruses demonstrated TAAAA instead of TATAA at the TATA box in the LTR. Of the 19 KSB patients, their sequence identities at the nucleotide level ranged from 89.8% to 97.1% from the lowest env gene to the highest pol gene. Other than the CRF02_AG viruses, no recombination events were noted in any of the 19 KSB patients, which is consistent with our previous studies on the pol, vif, and nef genes. Except for one strain, all of the strains were classified as non-syncytium-inducing strains. This is the first report to describe near full-length KSB.
To investigate the surgical and oncological outcomes of laparoscopic surgery compared with laparotomy for the treatment of early-stage ovarian cancer.
Data from patients who underwent surgical management for early-stage ovarian cancer between 2006 and 2012 were retrospectively reviewed. All patients presented with stage I or II disease, and underwent comprehensive staging surgery consisting of a total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, omentectomy, and peritoneal cytology.
Seventy-seven patients who underwent laparoscopic surgery (24 patients) or laparotomy (53 patients) were identified. Surgery for none of the patients was converted from laparoscopy to laparotomy. The mean operation time was shorter and the estimated blood loss was lower in the laparoscopy group than in the laparotomy group, though the differences were not statistically significant (193 min vs. 224 min, p=0.127; 698 mL vs. 973 mL, p=0.127). There were no differences in the intraoperative or postoperative complications. During a mean follow-up period of 31 months, tumor recurrence occurred in 4 patients: 2 (8.3%) in the laparoscopy group and 2 (3.8%) in the laparotomy group. The mean disease-free survival was 59 months after laparoscopy and 66 months after laparotomy (p=0.367).
Laparoscopic surgery seems to be adequate and feasible for the treatment of early-stage ovarian cancer with comparable results to laparotomy in terms of the surgical outcomes and oncological safety.
Early-stage ovarian cancer; Laparoscopy surgery; Laparotomy staging
Cholinergic urticaria is a type of physical urticaria characterized by heat-associated wheals. Several reports are available about cholinergic urticaria; however, the clinical manifestations and pathogenesis are incompletely understood.
The purpose of this study was to investigate the clinical characteristics of cholinergic urticaria in Korea.
We performed a retrospective study of 92 patients with cholinergic urticaria who were contacted by phone and whose diagnoses were confirmed by the exercise provocation test among those who had visited The Catholic University of Korea, Catholic Medical Center from January 2001 to November 2010.
All 92 patients were male, and their average age was 27.8 years (range, 17~51 years). Most of the patients had onset of the disease in their 20s and 30s. Non-follicular wheals were located on the trunk and upper extremities of many patients, and the symptoms were aggravated by exercise. Eight patients showed general urticaria symptoms and 15 had accompanying atopic disease. Forty-three patients complained of seasonal aggravation. Most patients were treated with first and second-generation antihistamines.
Dermatologists should consider these characteristics in patients with cholinergic urticaria. Further investigation and follow-up studies are necessary to better understand the epidemiological and clinical findings of cholinergic urticaria.
Cholinergic; Epidemiology; Phenotype; Signs and symptoms; Urticaria
Angiosarcoma is a highly malignant vascular tumor of endothelial origin. Initially, a cutaneous manifestation presents as a singular or multifocal bruise-like patches on the skin, most frequently on the face, the scalp or the neck regions. On progression, the lesions become violaceous, and ill-defined spongy nodular tumors appear. Our patient was a 71-year-old man with a previous history of angiosarcoma on the right forehead and was treated with an excision and local radiation 3 years ago. Several months after the treatment, a dark brownish to violaceous patch with edema arose from the right upper eyelid and spread out to the lower eyelid. Clinically, an ecchymosis caused by trauma or other hemangioma was suspected more than a recurrent angiosarcoma. Histopathologic examinations including immunohistochemical studies were consistent with cutaneous angiosarcoma. Herein, we report a rare case of a recurrent isolated angiosarcoma without the recurrence of a primary lesion.
Angiosarcoma; Ecchymosis; Eyelids
Congenital self-healing reticulohistiocytosis (CSHRH) is a rare, cutaneous, self-limited form of Langerhans cell histiocytosis. Whereas multiple lesions are common, a solitary lesion is rare. A 14-day-old neonate presented with a solitary, 5-mm, oval, reddish, and eroded papule with crust on the left thigh that had existed since birth. No systemic involvement was found. Histopathology revealed dense infiltration of large histiocytes with scattered eosinophils and lymphocytes in the dermis. Immunohistochemistry showed S-100 and CD1a positivity. Two months later, the skin lesion involuted spontaneously, without evidence of recurrence and extracutaneous involvement. On the basis of the characteristic clinical course and typical histopathological findings, a diagnosis of solitary CSHRH was made.
Hashimoto-Pritzker syndrome; Histiocytosis; Langerhans-cell
Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs.
A 28-year-old male patient with occipito-atlanto-axial instability underwent a cervical fusion with posterior technique. Post-operatively, the endotracheal tube (ETT) was removed, and the patient was transferred to the intensive care unit. After transfer, an upper airway obstruction developed and reintubations with a laryngoscope were attempted but failed. We inserted a #4 proseal laryngeal mask airway (LMA) and passed a 5.0 mm ETT through the LMA with the aid of a fiberoptic bronchoscope. We passed a tube exchanger through the 5.0 mm ETT and exchanged it with a 7.5 mm ETT. This method may be a useful alternative for difficult tracheal intubations.
Airway obstruction; Bronchoscopes; Cervical vertebrae; Laryngeal masks; Spinal fusion; Tube exchanger