We describe 2 cases in which radiographic evidence of thromboembolic events was obtained during germ cell tumor diagnosis. There was no evidence of coagulation factor abnormalities or contributory procedures or drugs in either patient. We used anticoagulation therapy for thrombolysis in one patient, but in the other, the thromboembolism resolved spontaneously.
Thromboembolism; Germ cell tumor; Chemotherapy
Imiquimod is known to exert its effects through Toll-like receptor 7 (TLR7) and/or TLR8, resulting in expression of proinflammatory cytokines and chemokines. Keratinocytes have not been reported to constitutively express TLR7 and TLR8, and the action of imiquimod is thought to be mediated by the adenine receptor, not TLR7 or TLR8. In this study, we revealed the expression of TLR7 in keratinocytes after calcium-induced differentiation. After addition of calcium to cultured keratinocytes, the immunological responses induced by imiquimod, such as activation of NF-κB and induction of TNF-α and IL-8, were more rapid and stronger. In addition, imiquimod induced the expression TLR7, and acted synergistically with calcium to induce proinflammatory cytokines. We confirmed that the responses induced by imiquimod were significantly inhibited by microRNAs suppressing TLR7 expression. These results suggest that TLR7 expressed in keratinocytes play key roles in the activation of NF-κB signaling by imiquimod, and that their modulation in keratinocytes could provide therapeutic potential for many inflammatory skin diseases.
BRCA1; p300; CARM1; DNA damage; protein methylation; p21; Gadd45; cell cycle; apoptosis; cancer
The superior shoulder suspensory complex (SSSC) is an extremely important structure composed of a ring of bone and soft tissues at the superior aspect of the shoulder. Double disruption leads to instability of the construct and usually requires operative treatment. Triple disruption of the SSSC is extremely rare and is encountered in high-energy trauma cases often in association with other injuries. The authors experienced a case of triple disruption involving the acromion, coracoid process, and acromioclavicular separation. This type of SSSC disruption is unlikely to have been caused by a single impact and is rather caused by multiple impacts during one traumatic event.
Superior shoulder suspensory complex; SSSC; triple disruption
An efficient clinical process guideline (CPG) modeling service was designed that uses an enhanced intelligent search protocol. The need for a search system arises from the requirement for CPG models to be able to adapt to dynamic patient contexts, allowing them to be updated based on new evidence that arises from medical guidelines and papers.
A sentence category classifier combined with the AdaBoost.M1 algorithm was used to evaluate the contribution of the CPG to the quality of the search mechanism. Three annotators each tagged 340 sentences hand-chosen from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) clinical guideline. The three annotators then carried out cross-validations of the tagged corpus. A transformation function is also used that extracts a predefined set of structural feature vectors determined by analyzing the sentential instance in terms of the underlying syntactic structures and phrase-level co-occurrences that lie beneath the surface of the lexical generation event.
The additional sub-filtering using a combination of multi-classifiers was found to be more effective than a single conventional Term Frequency-Inverse Document Frequency (TF-IDF)-based search system in pinpointing the page containing or adjacent to the guideline information.
We found that transformation has the advantage of exploiting the structural and underlying features which go unseen by the bag-of-words (BOW) model. We also realized that integrating a sentential classifier with a TF-IDF-based search engine enhances the search process by maximizing the probability of the automatically presented relevant information required in the context generated by the guideline authoring environment.
Knowledge Bases; Data Mining; Natural Language Processing
The aim of this study was to assess the efficacy and safety of monthly oral 150 mg ibandronate in women with postmenopausal osteoporosis (PMO).
A systematic review and meta-analysis were performed to determine treatment efficacy and safety outcomes between monthly oral 150 mg ibandronate and weekly 70 mg alendronate, daily 2.5 mg ibandronate, and a placebo.
Eight randomized controlled trials were included in this systematic review and meta-analysis. Once-monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, showing increased bone mineral density (BMD) in both the lumbar spine and total hip. Pooled data from two cross-over trials showed that significantly more women with PMO preferred once-monthly ibandronate therapy to once-weekly alendronate therapy (relative risk [RR], 2.422; 95% confidence interval [CI], 2.111 to 2.825; p < 1 × 10-8) and found the monthly ibandronate regimen more convenient than the weekly alendronate regimen (RR, 3.096; 95% CI, 2.622 to 3.622; p < 1 × 10-8). Monthly 150 mg ibandronate therapy resulted in a significantly higher change in BMD of the lumbar spine than with the placebo. A once monthly 150 mg regimen produced greater increases in lumbar spine, total hip, femoral neck, and trochanter BMD than daily treatment, with a similar incidence of adverse events between the groups.
Once monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, and patients strongly preferred the convenience of monthly ibandronate over weekly alendronate. Monthly 150 mg ibandronate was superior to, and as well tolerated as, the daily treatment.
Ibandronic acid; Efficacy; Safety; Osteoporosis; Review
To investigate if Lactobacillus casei cell wall extract (LCWE)-induced Kawasaki Disease (KD) accelerates atherosclerosis in hypercholesterolemic mice.
Method and Resuslts
Apoe−/− or Ldlr−/− mice were injected with LCWE (KD mice) or PBS, fed high fat diet for 8 weeks, and atherosclerotic lesions in aortic sinuses (AS), arch (AC) and whole aorta were assessed. KD mice had larger, more complex aortic lesions with abundant collagen, and both extracellular and intracellular lipid and foam cells, compared to lesions in control mice despite similar cholesterol levels. Both Apoe−/− KD and Ldlr−/− KD mice showed dramatic acceleration in atherosclerosis vs. controls, with increases in en face aortic atherosclerosis and plaque size in both the AS and AC plaques. Accelerated atherosclerosis was associated with increased circulating IL-12p40, IFN-γ, TNF-α, and increased macrophage, DC, and T cell recruitment in lesions. Furthermore, daily injections of the IL-1Ra, which inhibits LCWE induced KD vasculitis, prevented the acceleration of atherosclerosis.
Our results suggest an important pathophysiologic link between coronary arteritis/vasculitis in the KD mouse model and subsequent atherosclerotic acceleration, supporting the concept that a similar relation may also be present in KD patients. These results also suggest that KD in childhood may predispose to accelerated and early atherosclerosis as adults.
atherosclerosis; coronary disease; Kawasaki Disease; Interleukin 1 beta; IL-1 Receptor antagonist; mouse model of Kawasaki; vasculitis
Acquired enamel pellicle (AEP) is a protein film that forms on the enamel surface of teeth by selective adsorption of proteins and peptides present in the mouth. This protein film forms the interface between enamel and the damage oral biofilm, which modulates the attachment of bacteria found in oral biofilm. The overall goal of this study was to gain insight into the biological formation of the human in vivo AEP. This study hypothesized that AEP is created by the formation of successive protein layers, which consist of initial binding to enamel and subsequent protein-protein interactions. This hypothesis was examined by observing quantitative and qualitative changes in pellicle composition during the first two hours of AEP formation in the oral cavity. Quantitative mass spectrometry approaches were used to generate an AEP protein profile for each time-point studied. Relative proteomic quantification was carried out for the 50 proteins observed in all four time-points. Notably, the abundance of important salivary proteins, such as histatin 1, decrease with increasing of the AEP formation, while other essential proteins such as statherin showed constant relative abundance in all time-points. In summary, this is the first study that investigates the dynamic process to the AEP formation by using proteomic approaches. Our data demonstrated that there are significant qualitative and quantitative proteome changes during the AEP formation, which in turn will likely impact the development of oral biofilms.
Functioning adrenocortical oncocytomas are extremely rare and most reported patients are 40-60 yr of age. To our knowledge, only 2 cases of functioning adrenocortical oncocytomas have been reported in childhood. We report a case of functioning adrenocortical oncocytoma in a 14-yr-old female child presenting with virilization. She presented with deepening of the voice and excessive hair growth, and elevation of plasma testosterone and dehydroepiandrosterone sulfate. She had an adrenalectomy. The completely resected tumor composed predominantly of oncocytes without atypical mitosis and necrosis. A discussion of this case and a review of the literature on this entity are presented.
Adrenal Cortex Neoplasms; Adenoma, Oxyphilic; Virilism; Child
Drug-induced neutropenia (DIN), particularly that in which antibiotic-dependent antineutrophil antibodies have been detected, is a rare disorder. We report the case of a child with pneumococcal pneumonia, who experienced severe neutropenia during various antibiotic treatments. We detected 4 kinds (cefotaxim, augmentin, vancomycin, and tobramycin) of antibiotic-dependent antineutrophil antibodies by using the mixed passive hemagglutination assay (MPHA) technique with this child.
Neutropenia; Antineutrophil Antibody; Anti-Bacterial Agents
The proportion of medical school graduates who pursue careers other than full-time clinical practice has increased in some countries as the physician’s role has evolved and diversified with the changing landscape of clinical practice and the advancement of biomedicine. Still, past studies of medical students’ career choices have focused on clinical specialties and little is known about their choice of non-clinical careers. The present study examined backgrounds, motivation and perceptions of medical students who intended non-clinical careers.
A questionnaire was administered to students at six Korean medical schools distributed across all provinces in the nation. The questionnaire comprised 40 items on respondents’ backgrounds, their motivation for and interest in the study of medicine, their perceptions of medical professions, and their career intentions. Data was analyzed using various descriptive and inferential statistics.
In total, 1,388 students returned the questionnaire (60% response rate), 12.3% of whom intended non-clinical careers (i.e., basic sciences, non-clinical medical fields, and non-medical fields). Those who planned non-clinical careers were comparable with their peers in their motivation for studying medicine and in their views of medical professions, but they were less interested in the study of medicine (P < 0.01). The two groups also differed significantly on their perceptions of what was uninteresting about the study of medicine (P < 0.01). The two groups were comparable in gender and entry-level ratios but their distributions across ages and years of study differed significantly (P < 0.01). A majority of respondents agreed with the statements that “it is necessary for medical school graduates to pursue non-clinical careers” and that “medical schools need to offer programs that provide information on such careers.” Still, our finding indicates that medical school curricula do not address such needs sufficiently.
Our study found some differences in backgrounds and perceptions of the study of medicine in medical students interested in non-clinical careers from their peers. Future studies are suggested to enhance our understanding of medical students” choice of non-clinical careers.
Although extracellular Ca2+ entry through the voltage-dependent Ca2+ channels plays an important role in the spontaneous phasic contractions of the pregnant rat myometrium, the role of the T-type Ca2+ channels has yet to be fully identified. The aim of this study was to investigate the role of the T-type Ca2+ channel in the spontaneous phasic contractions of the rat myometrium. Spontaneous phasic contractions and [Ca2+]i were measured simultaneously in the longitudinal strips of female Sprague-Dawley rats late in their pregnancy (on day 18~20 of gestation: term=22 days). The expression of T-type Ca2+ channel mRNAs or protein levels was measured. Cumulative addition of low concentrations (<1 µM) of nifedipine, a L-type Ca2+ channel blocker, produced a decrease in the amplitude of the spontaneous Ca2+ transients and contractions with no significant change in frequency. The mRNAs and proteins encoding two subunits (α1G, α1H) of the T-type Ca2+ channels were expressed in longitudinal muscle layer of rat myometrium. Cumulative addition of mibefradil, NNC 55-0396 or nickel induced a concentration-dependent inhibition of the amplitude and frequency of the spontaneous Ca2+ transients and contractions. Mibefradil, NNC 55-0396 or nickel also attenuated the slope of rising phase of spontaneous Ca2+ transients consistent with the reduction of the frequency. It is concluded that T-type Ca2+ channels are expressed in the pregnant rat myometrium and may play a key role for the regulation of the frequency of spontaneous phasic contractions.
Calcium channels; Nickel; Mibefradil; NNC 55-0396; Spontaneous contractility
Soft tissue defects of the posterior heel of the foot present difficult reconstructive problems. This paper reports the authors' early experience of five patients treated with a lateral calcaneal artery adipofascial flap.
Between 2003 and 2007, five patients (3 males and 2 females) with soft-tissue defects over the posterior heel underwent a reconstruction using a lateral calcaneal artery adipofascial flap and a full-thickness skin graft. The flap sizes ranged from 3.5 × 2.5 cm to 5.5 × 4.0 cm.
All five flaps survived completely with no subsequent breakdown of the grafted skin, even after regularly wearing normal shoes. The adipofascial flap donor sites were closed primarily in all patients.
Lateral calcaneal artery adipofascial flaps should be included in the surgical armamentarium to cover difficult wounds of the posterior heel of the foot. These flaps do not require the sacrifice of a major artery to the leg or foot, they are relatively thin with minimal morbidity at the donor site, and leave a simple linear scar over the lateral aspect of the foot.
Foot; Posterior heel; Soft tissue defect; Lateral calcaneal artery adipofascial flap
The clinical findings of fever and skin rash with or without evidence of fluid retention, which mimic engraftment syndrome, have been observed during the pre-engraftment period in patients undergoing hematopoietic stem cell transplantation. In order to characterize this newly observed clinical syndrome called pre-engraftment syndrome (pES), we retrospectively analyzed the clinical records of 50 patients. Three out of 14 patients (23.1%) who underwent cord blood stem cell transplantation developed non-infectious fever, skin rash, and tachypnea 4-15 days prior to neutrophil engraftment. Two patients spontaneously recovered with fluid restriction and oxygen inhalation. One patient died of a complicated pulmonary hemorrhage in spite of aggressive supportive therapy and steroid treatment. Four out of 23 patients (17.4%) who underwent allogeneic bone marrow transplantation developed non-infectious fever and skin rash 4 to 5 days prior to neutrophil engraftment. All four of these patients recovered with only steroid treatment. These characteristic findings were not observed in patients who had undergone autologous peripheral blood stem cell transplantation. Interestingly, the speed of neutrophil engraftment was significantly faster for the patients suffering from pre-engraftment syndrome. The close observation and further pathophysiological research are required to better understand this syndrome.
Engraftment Syndrome; Hematopoietic Stem Cell Transplantation
The DNA damage response (DDR) involves both the control of DNA damage repair and signaling to cell cycle checkpoints. Therefore, unraveling the underlying mechanisms of the DDR is important for understanding tumor suppression and cellular resistance to clastogenic cancer therapeutics. Because the DDR is likely to be influenced by chromatin regulation at the sites of DNA damage, we investigated the role of heterochromatin protein 1 (HP1) during the DDR process. We monitored double-strand breaks (DSBs) using the γH2AX foci marker and found that depleting cells of HP1 caused genotoxic stress, a delay in the repair of DSBs and elevated levels of apoptosis after irradiation. Furthermore, we found that these defects in repair were associated with impaired BRCA1 function. Depleting HP1 reduced recruitment of BRCA1 to DSBs and caused defects in two BRCA1-mediated DDR events: (i) the homologous recombination repair pathway and (ii) the arrest of cell cycle at the G2/M checkpoint. In contrast, depleting HP1 from cells did not affect the non-homologous end-joining (NHEJ) pathway: instead it elevated the recruitment of the 53BP1 NHEJ factor to DSBs. Notably, all three subtypes of HP1 seemed to be almost equally important for these DDR functions. We suggest that the dynamic interaction of HP1 with chromatin and other DDR factors could determine DNA repair choice and cell fate after DNA damage. We also suggest that compromising HP1 expression could promote tumorigenesis by impairing the function of the BRCA1 tumor suppressor.
Due to the exquisite specificity and potency of the immune system, vaccination is in theory the most precise and powerful approach for controlling cancer. However, current data from clinical trials indicate that vaccination rarely yields significant benefits for cancer patients in terms of tumor progression and long-term survival. The poor clinical outcomes of vaccination are primarily caused by mechanisms of immune tolerance, especially within the tumor microenvironment. Here we report that vaccination drives the evolution of tumor cells towards an immune-resistant and stem-like phenotype that promotes tumor growth and nullifies the cytotoxic T lymphocyte (CTL) response. The emergence of this phenotype required the transcription factor Nanog, which is induced as a consequence of immune selection. Nanog expression enhanced the stem-like features of tumor cells and protected them from killing by tumor-reactive CTLs. Delivery of siNanog into tumor-bearing mice rendered the tumor vulnerable to immune surveillance and strongly suppressed its growth. Together, our findings demonstrate tumor adaptation to vaccination through gain of an immune-resistant, stem-like phenotype and identify Nanog as a central molecular target in this process. Future vaccination technology should consider Nanog an important target to enhance the immunotherapeutic response.
Cancer stem cell; immune escape; vaccination; human papillomavirus (HPV)
Kawasaki disease (KD) is the most common cause of acute vasculitis and acquired cardiac disease in US children. Untreated, children may develop coronary artery aneurysms, myocardial infarction and sudden death as a result of the illness. Up to a third of KD patients fail to respond to intravenous gammaglobulin (IVIG), the standard therapy, and alternative treatments are being investigated. Genetic studies have indicated a possible role for IL-1β in KD. We therefore explored the role of IL-1β in a murine model of KD.
Methods and Results
Using an established mouse model of KD that involves injection of Lactobacillus casei cell wall extract (LCWE), we investigated the role of IL- 1β and caspase-1 (activated by the inflammasome and required for IL-1β maturation) in coronary arteritis, and evaluated the efficacy of IL-1 receptor antagonist (IL-1Ra) as a potential treatment. LCWE-induced IL-1β maturation and secretion was dependent on the NLRP3 inflammasome in macrophages. Both caspase1-deficient and IL-1R-deficient mice were protected from LCWE-induced coronary lesions. Injection of recombinant IL-1β to caspase-1-deficient mice restored the ability of LCWE to cause coronary lesions in response to LCWE. Furthermore, daily injections of the IL-1Ra prevented LCWE-mediated coronary lesions, up to three days after LCWE injection.
Our results strongly suggest that caspase-1 and IL-1β play critical roles in the development of coronary lesions in this KD mouse model, blocked by IL-1Ra. Therefore, anti-IL-1β treatment strategies may constitute an effective, more targeted treatment of KD to prevent coronary lesions.
We assessed the cytokine combinations that are best for ex vivo expansion of cord blood (CB) and the increment for cell numbers of nucleated cells, as well as stem cells expressing homing receptors, by an ex vivo expansion of cryopreserved and unselected CB. Frozen leukocyte concentrates (LC) from CB were thawed and cultured at a concentration of 1×105/mL in media supplemented with a combination of SCF (20 ng/mL)+TPO (50 ng/mL)+FL (50 ng/mL)±IL-6 (20 ng/mL)±G-CSF (20 ng/mL). After culturing for 14 days, the expansion folds of cell numbers were as follows: TNC 22.3±7.8~26.3±4.9, CFU-GM 4.7±5.1~11.7±2.6, CD34+CD38- cell 214.0±251.9~464.1±566.1, CD34+CXCR4+ cell 4384.5±1664.7~7087.2±4669.3, CD34+VLA4+ cell 1444.3±1264.0~2074.9±1537.0, CD34+VLA5+ cell 86.2±50.9~113.2±57.1. These results revealed that the number of stem cells expressing homing receptors could be increased by an ex vivo expansion of cryopreserved and unselected CB using 3 cytokines (SCF, TPO, FL) only. Further in vivo studies regarding the engraftment after expansion of the nucleated cells, as well as the stem cells expressing homing receptors will be required.
Receptors, Lymphocyte Homing; Ex Vivo Expansion; Cryopreservation; Fetal Blood; Cytokines; Granulocyte Colong-Stimulating Factor; Thrombopoietin; Interleukin-6: Antigen, CD34
Homing-associated cell adhesion molecules (H-CAM) on the CD34+ cells play an important role for the engraftment process following hematopoietic stem cell transplantation (HSCT). However, it seems that not only CD34+ cells but also other nucleated cells (NCs) with H-CAM could be implicated in the engraftment process and the proliferation of hematopoietic stem cells. We investigated the differences of H-CAM and cell cycle status on the NCs in cord blood (CB), bone marrow (BM), and mobilized peripheral blood (PB). The proportions of CXCR4+ cells within the NC populations were greater in CB than in PB or BM (p=0.0493), although the proportions of CXCR4+, CD44+, and CD49d+ cells within the CB CD34+ cell populations were same within BM or PB. A lower proportion of CD34+CD49d+ cells within the CD34+ cell populations was more noted in CB than in PB or BM (p=0.0085). There were no differences in cell cycle status between CB and BM or PB. Our results suggest that the migrating potential of CB would be enhanced with increased CXCR4 expression on the NCs, but the adhesion potential of CB CD34+ cells would be less than that of PB and BM. These findings may help explain why the lower cell dose is required and engraftment is delayed in cord blood stem cell transplantation.
Cell Adhesion Molecules; Nucleated Cells; Erythrocytes; Bone Marrow; Peripheral Blood; Fetal Blood
Clinical Practice Guidelines (CPGs) are an effective tool for minimizing the gap between a physician's clinical decision and medical evidence and for modeling the systematic and standardized pathway used to provide better medical treatment to patients.
In this study, sentences within the clinical guidelines are categorized according to a classification system. We used three clinical guidelines that incorporated knowledge from medical experts in the field of family medicine. These were the seventh report of the Joint National Committee (JNC7) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure from the National Heart, Lung, and Blood Institute; the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults from the same institution; and the Standards of Medical Care in Diabetes 2010 report from the American Diabetes Association. Three annotators each tagged 346 sentences hand-chosen from these three clinical guidelines. The three annotators then carried out cross-validations of the tagged corpus. We also used various machine learning-based classifiers for sentence classification.
We conducted experiments using real-valued features and token units, as well as a Boolean feature. The results showed that the combination of maximum entropy-based learning and information gain-based feature extraction gave the best classification performance (over 98% f-measure) in four sentence categories.
This result confirmed the contribution of the feature reduction algorithm and optimal technique for very sparse feature spaces, such as the sentence classification problem in the clinical guideline document.
Knowledge Bases; Data Mining; Information Storage and Retrieval
Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Absence of definitive diagnostic markers limits the accuracy of clinical evaluations of suspected KD with significant increases in morbidity. In turn, incomplete understanding of its molecular pathogenesis hinders the identification of rational targets needed to improve therapy. We used high-accuracy mass spectrometry proteomics to analyse over 2000 unique proteins in clinical urine specimens of patients with KD. We discovered that urine proteomes of patients with KD, but not those with mimicking conditions, were enriched for markers of cellular injury such as filamin and talin, immune regulators such as complement regulator CSMD3, immune pattern recognition receptor muclin, and immune cytokine protease meprin A. Significant elevations of filamin C and meprin A were detected in both the serum and urine in two independent cohorts of patients with KD, comprised of a total of 236 patients. Meprin A and filamin C exhibited superior diagnostic performance as compared to currently used markers of disease in a blinded case-control study of 107 patients with suspected KD, with receiver operating characteristic areas under the curve of 0.98 (95% confidence intervals [CI] of 0.97–1 and 0.95–1, respectively). Notably, meprin A was enriched in the coronary artery lesions of a mouse model of KD. In all, urine proteome profiles revealed novel candidate molecular markers of KD, including filamin C and meprin A that exhibit excellent diagnostic performance. These disease markers may improve the diagnostic accuracy of clinical evaluations of children with suspected KD, lead to the identification of novel therapeutic targets, and allow the development of a biological classification of Kawasaki disease.
biomarker; Kawasaki disease; mass spectrometry; vasculitis; urinary proteome
We evaluated the effect of human parathyroid hormone (hPTH) on the engraftment and/or in vivo expansion of hematopoietic stem cells in an umbilical cord blood (UCB)-xenotransplantation model. In addition, we assessed its effect on the expression of cell adhesion molecules.
Materials and Methods
Female NOD/SCID mice received sublethal total body irradiation with a single dose of 250 cGy. Eighteen to 24 hours after irradiation, 1×107 human UCB-derived mononuclear cells (MNCs) and 5×106 human UCB-derived mesenchymal stem cells (MSCs) were infused via the tail vein. Mice were randomly divided into three groups: Group 1 mice received MNCs only, Group 2 received MNCs only and were then treated with hPTH, Group 3 mice received MNCs and MSCs, and were treated with hPTH.
Engraftment was achieved in all the mice. Bone marrow cellularity was approximately 20% in Group 1, but 70-80% in the hPTH treated groups. Transplantation of MNCs together with MSCs had no additional effect on bone marrow cellularity. However, the proportion of human CD13 and CD33 myeloid progenitor cells was higher in Group 3, while the proportion of human CD34 did not differ significantly between the three groups. The proportion of CXCR4 cells in Group 3 was larger than in Groups 1 and 2 but without statistical significance.
We have demonstrated a positive effect of hPTH on stem cell proliferation and a possible synergistic effect of MSCs and hPTH on the proportion of human hematopoietic progenitor cells, in a xenotransplantation model. Clinical trials of the use of hPTH after stem cell transplantation should be considered.
Umbilical cord blood; parathyroid hormone; bone marrow niches
A selective 5-hydroxytryptamine (5-HT) type 3 receptor antagonist, ramosetron, inhibits stress-induced abnormal defecation in animals and is currently used as a therapeutic drug for irritable bowel syndrome with diarrhea. The aim of this study is to investigate the effect of ramosetron on altered gastrointestinal (GI) transit.
Male guinea pigs weighing approximately 300 g were used. The effect of ramosetron was investigated on altered GI transit induced by thyrotropin-releasing hormone (TRH), 5-HT, or mustard oil (MO). GI transit was evaluated by the migration of charcoal mixture from the pylorus to the most distal point, and expressed as a percentage (%) of charcoal migration (cm) of the total length of total small intestine (cm).
The average charcoal transit was 51.3 ± 20.1% in the control (vehicle) group, whereas in the ramosetron group charcoal moved 56.6 ± 21.9%, 46.9 ± 9.14% and 8.4 ± 5.6% of the total small intestine at the concentrations of 10, 30 and 100 µg/kg, respectively. GI transit after administration of TRH (100 µg/kg), 5-HT (10 mg/kg) or MO (10 mg/kg) was accelerated compared to vehicle (5-HT, 94.9 ± 9.22%; TRH, 73.4 ± 14.7%; MO, 81.0 ± 13.7%). Ramosetron inhibited GI transit altered by 5-HT, TRH or MO.
Ramosetron modulated GI transit. We suggest that ramosetron may be therapeutically useful for those with accelerated upper GI transit.
Gastrointestinal transit; Mustard oil; Ramosetron; Serotonin 5-HT3 receptor antagonist; Thyrotropin-releasing hormone