Latent metabolic bone disease, skeletal dysplasia and other conditions related to low bone formation among 38 patients with subtrochanteric femoral fractures: a retrospective observational study.

Subtrochanteric femoral fracture is rare and intractable due to the possible association with low bone formation. Retrospective analysis of 38 patients with subtrochanteric femoral fractures revealed that four patients suffered from disorders related to low bone formation and there were specific treatments for two of them. PURPOSE: The main aim of this study was to detect latent metabolic bone diseases and skeletal dysplasia associated with low bone formation among patients with morphologic atypical femoral fracture (AFF). A second aim was to evaluate the frequency of recognized risk factors, such as antiresorptive agents, glucocorticoids, and age. METHODS: Clinical information was retrospectively analyzed among 38 Japanese patients who were admitted to the Department of Orthopedic Surgery and Spinal Surgery and the Division of Emergency and Critical Care Medicine at the University of Tokyo Hospital with diagnoses of subtrochanteric fractures between February 2012 and March 2022. RESULTS: Among 38 patients (including 30 females), 21 patients were aged 75 and over. Ten patients had past oral glucocorticoid use, and 18 had past antiresorptive agent use. Two patients were diagnosed with hypophosphatemic osteomalacia after the development of fractures. One patient was suspected to be a carrier of a loss-of-function variant of alkaline phosphatase, biomineralization associated (ALPL), and one other patient had previously been genetically diagnosed with pycnodysostosis. Among four patients with a diagnosis or suspicion of these metabolic bone diseases and skeletal dysplasia, four had past clinical fractures, two had past subtrochanteric femoral fractures, and two had subtrochanteric femoral fractures on both sides. CONCLUSION: If clinicians encounter patients with morphologic AFF, latent diseases related to low bone formation should be carefully differentiated because appropriate treatment may prevent delayed union and recurrent fractures. Additionally, it may be desirable to exclude these bone diseases in advance before initiating long-term use of antiresorptive agents in osteoporotic patients by screening with serum alkaline phosphatase levels to reduce the risk of morphologic AFF.

Hypopituitarism with secondary adrenocortical insufficiency and arginine vasopressin deficiency due to hypophysitis after COVID-19 vaccination: a case report.

BACKGROUND: Although vaccination against coronavirus disease (COVID-19) has several side effects, hypopituitarism due to hypophysitis has rarely been reported. CASE PRESENTATION: An 83-year-old healthy woman, who had received her fourth COVID-19 vaccine dose 2 days before admission, presented to the emergency department with difficulty moving. On examination, impaired consciousness (Glasgow Coma Scale: 14) and fever were observed. Computed tomography and magnetic resonance imaging of the head revealed swelling from the sella turcica to the suprasellar region. Her morning serum cortisol level was low (4.4 µg/dL) and adrenocorticotropic hormone level was normal (21.6 pg/mL). Central hypothyroidism was also suspected (thyroid stimulating hormone, 0.46 µIU/mL; free triiodothyronine, 1.86 pg/mL; free thyroxine, 0.48 ng/dL). Secondary adrenocortical insufficiency, growth hormone deficiency, delayed gonadotropin response, and elevated prolactin levels were also observed. After administration of prednisolone and levothyroxine, her consciousness recovered. On the 7th day of admission, the patient developed polyuria, and arginine vasopressin deficiency was diagnosed using a hypertonic saline test. On the 15th day, the posterior pituitary gland showed a loss of high signal intensity and the polyuria resolved spontaneously. On the 134th day, the corticotropin-releasing hormone loading test showed a normal response; however, the thyrotropin-releasing hormone stimulation test showed a low response. The patient's disease course was stable with continued thyroid and adrenal corticosteroid supplementation. CONCLUSIONS: Herein, we report a rare case of anterior hypopituitarism and arginine vasopressin deficiency secondary to hypophysitis following COVID-19 vaccination.

Categorization using the Dementia Assessment Sheet for Community-Based Integrated Care System 8-items (DASC-8) based on cognitive function and activities of daily living predicts frailty, disability and mortality in older adults.

AIM: This longitudinal study aimed to determine whether categorization by the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) is associated with risk of frailty onset, disability, and mortality. METHODS: We analyzed longitudinal data from outpatients aged 65 years and older evaluated for the DASC-8 at the Frailty Clinic. The outcomes during the 3-year follow-up period were (Study A) frailty onset (Kihon Checklist ≥8) and (Study B) disability (new certification of nursing care needs) or mortality. Multivariate Cox regression analyses were performed to examine independent associations between the DASC-8 category and outcomes, and hazard ratios and 95% confidence intervals (CIs) were calculated after adjustment for age, sex, and the presence or absence of diabetes, hypertension, and dyslipidemia. RESULTS: (Study A) Out of the 216 patients without frailty in Categories I or II at baseline, 40 (20.4%) and 11 (55.0%) developed frailty, respectively. The adjusted hazard ratio was 3.62 (95% CI: 1.69-7.76, P < 0.001). (Study B) Out of the 350 patients who did not require long-term care at baseline, disability or death occurred for 20 (7.3%) in Category I, 14 (23.0%) in Category II, and 9 (56.3%) in Category III. The adjusted hazard ratios were 2.40 (Category I vs. II; 95% CI: 1.13-5.11, P = 0.023) and 5.43 (Category I vs. III; 95% CI: 2.23-13.3, P < 0.001). CONCLUSION: Categorization according to DASC-8 is associated with the risk of frailty, disability, and mortality in older patients. Geriatr Gerontol Int 2024; 24: 150-155.

The Effect of Asfotase Alfa on Plasma and Urine Pyrophosphate Levels and Pseudofractures in a Patient With Adult-Onset Hypophosphatasia.

Hypophosphatasia (HPP) is an inherited disease caused by variants of the ALPL gene encoding tissue-nonspecific alkaline phosphatase. Adult-onset HPP (adult HPP), known as a mild form of HPP, develops symptoms involving osteomalacia after the age of 18 years. Asfotase alfa (AA) is a modulated recombinant human alkaline phosphatase (ALP) that has been established as a first-line therapy for severe forms of HPP, such as perinatal and infantile forms. We described a 64-year-old female who presented with pseudofractures in bilateral femur diaphyses and impaired mobility. Low serum ALP activity and a high concentration of urine phosphoethanolamine indicated the diagnosis of HPP, which was confirmed by the identification of a homozygous variant in the ALPL gene (c.319G > A; p.Val107Ile). An in vitro transfection experiment to measure the ALP activity of this novel variant protein was performed, resulting in 40% of the residual enzymatic activity compared with the wild type. AA was initiated to facilitate the union of pseudofracture and to improve mobility. After 6 months, radiographic images revealed the disappearance of fracture lines, and improvement of ambulatory ability was confirmed by the 6-minute walk test (525 to 606 m). The EQ-5D-5L index was also improved (0.757 to 0.895). Within a follow-up period, the levels of urine pyrophosphate corrected by urine creatinine (uPPi/Cre) declined in parallel with the level of plasma PPi (plasma PPi: 6.34 to 1.04 µM, uPPi/Cre: 226.8 to 75.4 nmol/mg). The beneficial effect of AA on pseudofracture healing in adult HPP was presented, although the application of AA should be restricted to patients exhibiting relatively severe manifestations. In addition, a novel pathogenic variant of the ALPL gene was identified with the supportive result of functional analysis. Furthermore, when monitoring patients with HPP treated with AA, uPPi/Cre might be a convenient substitute for plasma PPi, which requires immediate filtration after blood sampling. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

The cross-sectional area of erector spinae muscle and the liver-to-spleen ratio are associated with frailty in older patients with diabetes: a cross-sectional study.

BACKGROUND: Older patients with diabetes mellitus are more susceptible to frailty. Although some imaging markers of appendicular skeletal muscle mass obtained using dual-energy X-ray absorptiometry or computed tomography (CT) imaging can reflect frailty status, the association between imaging indices obtained by abdominal CT scans and frailty in older inpatients has not been reported. METHODS: A total of 151 older inpatients with diabetes mellitus (median age, 79 years; men, 42%) who underwent abdominal CT scans close to the admission date were studied to examine the associations between abdominal CT indices and frailty. Two frailty definitions were used: the modified Cardiovascular Health Study (mCHS) criteria and Kihon Checklist (KCL) criteria. Using the imaging analysis software SYNAPSE VINCENT®, we compared the cross-sectional areas (CSA) of four truncal muscles (erector spinae, iliopsoas, rectus abdominis, and abdominal oblique muscles) and the liver-to-spleen ratio (L/S), the ratio of the CT values of the liver and spleen between frail and non-frail patients. The muscle areas that showed the strongest associations with frailty were also investigated in relation to grip strength and walking speed. Finally, multivariate binominal logistic regression analyses were performed to assess the independent associations of CSA of muscle and L/S with the prevalence of frailty. RESULTS: The prevalence of frailty defined by the mCHS and KCL criteria was 55% and 52%, respectively. The CSA of the erector spinae muscle was most significantly associated with frailty, and was significantly smaller in both sexes of mCHS-defined frail patients and in men with KCL-defined frailty. The CSA of erector spinae muscle was also positively correlated with grip strength and walking speed. In contrast, the L/S was higher in men with KCL-defined frailty. Multivariate logistic regression analyses revealed that the CSA of the erector spinae muscle was independently associated with mCHS-defined frailty in women, and the L/S was associated with KCL-defined frailty in men. CONCLUSIONS: The CSA of erector spinae muscle and low liver fat content could be indices of frailty in older patients with diabetes.

[A geriatric case of hyperosmolar hyperglycemic state with osmotic demyelination syndrome that manifested with dysphagia].

The patient was an 84-year-old man who had been on insulin therapy for type 2 diabetes mellitus for 55 years. He had undergone bile duct stenting to avoid obstruction due to adenocarcinoma of the bile duct. The patient had suffered from fever and anorexia for two weeks, and had subsequently stopped insulin therapy. Since he showed signs of impaired consciousness, he was taken to the emergency room, and was diagnosed with a hyperosmotic hyperglycemic state (HHS) based on the following laboratory findings: blood glucose, 632 mg/dL; plasma osmolality, 391 mOsm/kg·H2O; and serum Na, 163 mEq/L, with urine ketone bodies±and sepsis (Klebsiella pneumoniae). He was therefore admitted to the hospital. His blood glucose and serum Na levels slowly improved following the administration of fluids, insulin, and antibiotics. The patient's consciousness disturbance also improved. However, on the third day after admission, dysphagia was newly observed when the patient resumed eating, and swallowing endoscopy revealed a delayed gag reflex and pharyngeal retention of saliva. Cranial magnetic resonance imaging showed a high-intensity area in the central pontine, which was considered to be caused by osmotic demyelination syndrome (ODS). The patient's oral intake ability recovered with swallowing rehabilitation. ODS is a rare complication of HHS. We report a case of HHS with ODS, in which the patient's chief complaint was dysphagia, which should be distinguished from other diseases.

Subclinical Atherosclerosis, Vascular Risk Factors, and White Matter Alterations in Diffusion Tensor Imaging Findings of Older Adults With Cardiometabolic Diseases.

White matter abnormalities may reflect cerebral microvessel disease. Diffusion tensor imaging (DTI) can help detect early changes in white matter integrity in each tract. However, studies investigating the relationship between subclinical atherosclerosis markers and white matter alterations in DTI findings are limited. This study aimed to examine associations between cardiovascular risk factors and indices of subclinical atherosclerosis-ankle brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and carotid artery intima-media thickness (IMT)-and altered white matter integrity in older patients. A total of 224 patients (aged ≥65 years) with cardiometabolic disease who underwent magnetic resonance imaging (MRI) and either plethysmography or cervical ultrasound at the start of the 3-year observational study period were included in this study. We measured fractional anisotropy (FA) and mean diffusivity (MD), which are indices of white matter integrity in seven white matter tracts. In a univariate analysis, lower ABI and higher baPWV values were associated with FA or MD abnormalities in several tracts, whereas IMT was scarcely associated with such change. In addition, high blood pressure and glycoalbumin/glycohemoglobin ratio (GA/HbA1c) and low body mass index (BMI) and triglyceride (TG) levels were associated with FA or MD abnormalities. In a multivariate analysis adjusted for age, sex, BMI, diastolic blood pressure, TG, and GA/HbA1c, the associations between ABI and FA or MD remained in all of either side of the following tracts: anterior thalamic radiation, forceps minor, inferior frontooccipital fasciculus (p < 0.001 for all) and superior longitudinal fasciculus (SLF; p < 0.05), whereas most of those between baPWV and FA or MD disappeared except for SLF (p < 0.05). These results indicate that low ABI could be an indicator of white matter abnormalities.

Successful treatment of eosinophilic otitis media associated with severe bronchial asthma with an anti-IL-5 monoclonal antibody, mepolizumab.

Eosinophilic otitis media (EOM), which is characterized by the accumulation of eosinophils in middle ear effusion and the middle ear mucosa, is a refractory type of otitis media that is often associated with asthma. Although an early diagnosis and appropriate treatment are necessary to prevent the progression of hearing loss in patients with EOM, there are currently no well-established treatments for this condition. We treated a 60-year-old male patient with asthma and EOM. The patient's asthma was poorly controlled, despite the use of high-dose inhaled corticosteroids, long-acting beta-agonist treatment, and the regular use of systemic corticosteroids. Mepolizumab, an anti-IL-5 monoclonal antibody, was started to treat the patient's refractory asthma. At 4 months after the initiation of mepolizumab treatment, the patient's asthma, hearing, and middle ear effusion improved. The present case suggests that mepolizumab therapy can control EOM and asthma.

No adverse effects detected for simultaneous whole-body exposure to multiple-frequency radiofrequency electromagnetic fields for rats in the intrauterine and pre- and post-weaning periods.

In everyday life, people are exposed to radiofrequency (RF) electromagnetic fields (EMFs) with multiple frequencies. To evaluate the possible adverse effects of multifrequency RF EMFs, we performed an experiment in which pregnant rats and their delivered offspring were simultaneously exposed to eight different communication signal EMFs (two of 800 MHz band, two of 2 GHz band, one of 2.4 GHz band, two of 2.5 GHz band and one of 5.2 GHz band). Thirty six pregnant Sprague-Dawley (SD) 10-week-old rats were divided into three groups of 12 rats: one control (sham exposure) group and two experimental (low- and high-level RF EMF exposure) groups. The whole body of the mother rats was exposed to the RF EMFs for 20 h per day from Gestational Day 7 to weaning, and F1 offspring rats (46-48 F1 pups per group) were then exposed up to 6 weeks of age also for 20 h per day. The parameters evaluated included the growth, gestational condition and organ weights of the dams; the survival rates, development, growth, physical and functional development, memory function, and reproductive ability of the F1 offspring; and the embryotoxicity and teratogenicity in the F2 rats. No abnormal findings were observed in the dams or F1 offspring exposed to the RF EMFs or to the F2 offspring for any of the parameters evaluated. Thus, under the conditions of the present experiment, simultaneous whole-body exposure to eight different communication signal EMFs at frequencies between 800 MHz and 5.2 GHz did not show any adverse effects on pregnancy or on the development of rats.

Multigenerational effects of whole body exposure to 2.14 GHz W-CDMA cellular phone signals on brain function in rats.

The present experimental study was carried out with rats to evaluate the effects of whole body exposure to 2.14 GHz band code division multiple access (W-CDMA) signals for 20 h a day, over three generations. The average specific absorption rate (SAR, in unit of W/kg) for dams was designed at three levels: high (<0.24 W/kg), low (<0.08 W/kg), and 0 (sham exposure). Pregnant mothers (4 rats/group) were exposed from gestational day (GD) 7 to weaning and then their offspring (F1 generation, 4 males and 4 females/dam, respectively) were continuously exposed until 6 weeks of age. The F1 females were mated with F1 males at 11 weeks old, and then starting from GD 7, they were exposed continuously to the electromagnetic field (EMF; one half of the F1 offspring was used for mating, that is, two of each sex per dam and 8 males and 8 females/group, except for all offspring for the functional development tests). This protocol was repeated in the same manner on pregnant F2 females and F3 pups; the latter were killed at 10 weeks of age. No abnormalities were observed in the mother rats (F0 , F1 , and F2 ) and in the offspring (F1 , F2 , and F3 ) in any biological parameters, including neurobehavioral function. Thus, it was concluded that under the experimental conditions applied, multigenerational whole body exposure to 2.14 GHz W-CDMA signals for 20 h/day did not cause any adverse effects on the F1 , F2 , and F3 offspring.

Seasonal allergic rhinitis affects sinonasal microbiota.

BACKGROUND: Microbes and allergens can stimulate the nasal mucosa, potentially leading to the development of acute bacterial rhinosinusitis (ABRS). This study was designed to determine if allergen exposure alters the sinonasal microbiome. METHODS: We performed a parallel observational study of healthy adults with seasonal allergic rhinitis (SAR; grass or tree, n = 20) or nonallergic subjects (n = 19). Microbiota specimens were obtained by endoscopy from the middle meatus and vestibule before and during the relevant season and were analyzed by terminal restriction fragment length polymorphism analysis. Differences in bacterial microbiota were assessed by standard ecological measures of bacterial diversity. Quality of life and symptom scores were recorded, and nasal lavages for eosinophils were performed. RESULTS: SAR subjects had increased nasal symptoms in season, impaired disease-specific quality of life, and increased nasal eosinophils, compared with no changes in nonallergic subjects. During the season, SAR subjects had a significantly greater variety of organisms in the middle meatus compared with nonallergic subjects (p < 0.036) and increased bacterial diversity (Shannon index, p < 0.013). We found a significant positive correlation between bacterial diversity in the middle meatus during the season and the nasal lavage eosinophil count of SAR subjects. There were no significant changes in the nasal vestibule (p > 0.05, all comparisons). CONCLUSION: The interaction of allergy and microbiota may affect the sinonasal physiology, with broad implications for several airway diseases. Characterization of the specific organisms involved using next-generation sequencing may clarify the relationship between allergic inflammation and ABRS. This finding may help explain why allergic inflammation predisposes to ABRS.

Effect of prednisone on nasal symptoms and peripheral blood T-cell function in chronic rhinosinusitis.

BACKGROUND: Systemic corticosteroids are the most effective anti-inflammatory drugs used for controlling chronic rhinosinusitis (CRS) symptoms. The potential mechanisms for their beneficial effects include increasing the number and function of T regulatory cells (Tregs), as reported in the local tissue post-intranasal steroid treatment. We investigated the effect of systemic corticosteroids on peripheral blood (PB) Tregs in subjects with CRS. METHODS: Twenty CRS subjects and 19 controls were recruited. PB mononuclear cells (PBMCs) were isolated from CRS subjects before and after systemic corticosteroid administration in the course of clinical treatment. Control subjects received no treatment and were studied at one visit. Nasal symptoms were recorded. CD4(+) CD25(+) Foxp3(+) cells (Tregs) were analyzed by flow cytometry. Messenger RNA (mRNA) levels for interferon γ (IFN-γ), interleukin 4 (IL-4), IL-10, IL-13, IL-17A, transforming growth factor ß1 (TGF-ß1), forkhead box P3 (FoxP3), and GATA-binding factor 3 (GATA-3) were measured in PBMCs using real-time polymerase chain reaction (PCR). RESULTS: CRS subjects reported improved nasal symptoms (p = 0.005) and significantly reduced PB Tregs after treatment with corticosteroids (p = 0.042). The transcript levels of IL-4 and GATA-3 were significantly higher in the CRS subjects at their first visit when compared to controls (p = 0.019 and p = 0.05, respectively). Corticosteroid treatment lowered the transcript levels of immunoregulatory transcription factors [FoxP3 (p = 0.048) and GATA-3 (p = 0.012)] and IFN-γ (p = 0.036) in PB. CONCLUSION: In contrast to prior work in local nasal tissue, our study reports reduced PB Tregs and decreased T helper 1 (T(H)1) and T(H)2 function after treatment with systemic corticosteroids. These data indicate that corticosteroid effects on Tregs in CRS are complex involving local signals in the tissue that are distinct from those in circulating cells.

Effects of electromagnetic fields emitted from W-CDMA-like mobile phones on sleep in humans.

In this study, we investigated subjective and objective effects of mobile phones using a Wideband Code Division Multiple Access (W-CDMA)-like system on human sleep. Subjects were 19 volunteers. Real or sham electromagnetic field (EMF) exposures for 3 h were performed before their usual sleep time on 3 consecutive days. They were exposed to real EMF on the second or third experimental day in a double-blind design. Sleepiness and sleep insufficiency were evaluated the next morning. Polysomnograms were recorded for analyses of the sleep variables and power spectra of electroencephalograms (EEG). No significant differences were observed between the two conditions in subjective feelings. Sleep parameters including sleep stage percentages and EEG power spectra did not differ significantly between real and sham exposures. We conclude that continuous wave EMF exposure for 3 h from a W-CDMA-like system has no detectable effects on human sleep.

Rhinosinusitis and asthma-microbiome and new perspectives.

PURPOSE OF REVIEW: Microbiome is one of the new perspectives in human health research, including airway diseases. There are several publications about the relationship of the microbiome and allergic diseases. Although pathogenesis of chronic rhinosinusitis (CRS) as well as its relationship with asthma has been widely investigated, the relationship of the microbiome and CRS is not yet well known. RECENT FINDINGS: The relationship between the hygiene hypothesis and microorganisms inside the human body and in the environment around it has been clearly shown. Furthermore, several researchers have reported that the microorganisms in the gut play a major role in regulating the immune cells that are of relevance to asthma and allergic diseases, such as Th1, Th2, Th17, Treg and dendritic cells as well as Toll-like receptors. Reduced contact of people with natural environmental features and biodiversity may adversely affect the human commensal microbiota and its immunomodulatory capacity.Some studies have shown a close relationship between CRS and Staphylococcus aureus, anaerobes and so on in the nasal cavity or paranasal sinuses, although the relationship between CRS and microorganisms in the gut has not been demonstrated. SUMMARY: In this review, we summarized about the microbiome, mainly in asthma and allergic diseases. The relationship between asthma and CRS has been clearly shown, and in particular, CRS with nasal polyps (CRSwNP) has been considered to be Th2-dominant. Studies examining environmental microbial exposure in populations at risk for CRS are necessary to improve our understanding of the role this factor plays in disease development.

Peripheral blood and tissue T regulatory cells in chronic rhinosinusitis.

BACKGROUND: The pathogenesis of chronic rhinosinusitis (CRS) has not been fully elucidated. Increased inflammatory cell infiltration and decreased numbers and/or impaired function of T regulatory cells (Tregs) have been reported. This study aimed to determine the role of Tregs in CRS in peripheral blood (PB) and sinus tissue. METHODS: Sinus tissue was obtained from 16 CRS subjects and 5 controls. PB from additional 16 CRS subjects and total 20 controls was obtained. Immunohistochemical analysis (CD3(+), CD4(+), CD8(+), and Treg [CD4(+)-FoxP3(+) and CD25(+)-FoxP3(+)] cells) of sinus tissue was performed. Percentage of PB Tregs (CD4(+)-CD25(+)-FoxP3(+) cells) was analyzed by flow cytometry. Spontaneous and phytohemagglutinin (PHA)-induced release of cytokines (IL-6, IL-4, IL-10, interferon gamma, transforming growth factor [TGF] beta1, and TNF-alpha) from PB mononuclear cells (PBMCs) was determined. RESULTS: PB flow cytometric analysis revealed a lower percentage of Tregs in subjects with CRS compared with healthy controls (p = 0.0003). Although no differences in the PB Treg counts were observed between the CRS subjects with nasal polyposis (CRSwNP) and without nasal polyposis (CRSsNP), immunohistochemical analysis performed on sinus tissue revealed a higher proportion of Tregs in CRSwNP subjects compared with CRSsNP (p < 0.05). Additionally, we failed to detect any Tregs from control sphenoid sinus tissue. Lower levels of regulatory cytokines (IL-10 and TGF-ß1) and higher levels of proinflammatory cytokines (TNF-α and IL-6) were found from PBMCs from CRS subjects compared with controls (p < 0.05). CONCLUSION: Our findings suggest that CRS subjects exhibit a decreased percentage of PB Tregs compared with normal controls. PBMCs from CRS subjects show a more proinflammatory and less regulatory phenotype.

[Effects of double-stranded RNA poly(I:C) on matrix metalloproteinase mRNA expression in human nasal polyp epithelial cells].

OBJECTIVE: Chronic rhinosinusitis was often exacerbated by viral infection. A disruption of the mechanisms that regulate the activity of matrix metalloproteinases (MMPs) during viral infection was one possible mechanism responsible for the exacerbation. The purpose of study was to achieve a better understanding of MMP expression in nasal epithelial cells after viral infection. METHODS: Human nasal epithelial cells were isolated from nasal polyp specimens obtained during endoscopic endonasal surgery in chronic rhinosinusitis patients. The expression of MMP-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 mRNA in primary human nasal polyp epithelial cells after double stranded RNA (ds RNA) stimulation were investigated. RESULTS: Among the genes whose expression was evaluated, only expression of MMP-9 mRNA increased significantly after dsRNA stimulation (22.61 +/- 5.47 fold increase, Z = -2.52, P = 0.012). CONCLUSIONS: The significant up-regulation of MMP-9 mRNA, which was not modulated by TIMP-1, was an additional source of increased proteolytic activity in virus-infected upper airways that might contribute to the exacerbation of chronic rhinosinusitis with nasal polyps.

Lack of adverse effects of whole-body exposure to a mobile telecommunication electromagnetic field on the rat fetus.

Abstract The recent steep increase in the number of users of cellular phones is resulting in marked increase of exposure of humans to radiofrequency electromagnetic fields (EMFs). Children are of particular concern. Our goal was to evaluate potential adverse effects of long-term whole-body exposure to EMFs simulating those from base stations for cellular phone communication. Pregnant rats were given low, high or no exposure. At the high level, the average specific absorption rate (SAR)for the dams was 0.066-0.093 W/kg. The SAR for the fetuses and the F(1) progeny was 0.068-0.146 W/kg. At the low level, the SARs were about 43% of these. The 2.14 GHz signals were applied for 20 h per day during the gestation and lactation periods. No abnormal findings were observed in either the dams or the F(1) generation exposed to the EMF or in the F(2) offspring. Parameters evaluated included growth, gestational condition and organ weights for dams and survival rates, development, growth, physical and functional development, hormonal status, memory function and reproductive ability of the F(1) offspring (at 10 weeks of age) along with embryotoxicity and teratogenicity in the F(2) rats. Thus, under our experimental conditions, whole-body exposure to 2.14 GHz for 20 h per day during gestation and lactation did not cause any adverse effects on pregnancy or the development of rats.

Glucocorticoid receptor immunoreactivity of eosinophils in nasal polyps.

CONCLUSION: The higher level of glucocorticoid receptor (GR) expression in cases of chronic sinusitis with bronchial asthma or allergic rhinitis suggests that glucocorticoids may exert a greater influence on eosinophils, thereby making them more effective in the treatment of polyps or chronic sinusitis. OBJECTIVES: The GR immunoreactivity of eosinophils in nasal polyps was investigated to elucidate the mechanism by which glucocorticoids interact with eosinophils. MATERIALS AND METHODS: Nasal polyp specimens were divided into 3 groups: 7 patients with chronic sinusitis alone (CS only group), 12 patients with chronic sinusitis complicated by perennial allergic rhinitis (CS/AR group), and 6 patients with chronic sinusitis complicated by bronchial asthma except for aspirin-induced asthma (CS/asthma group). Immunofluorescent staining with an anti-GR polyclonal antibody and anti-major basic protein (MBP) monoclonal antibody was used. RESULTS: The total number of MBP+ cells, GR+ cells, and MBP+/GR+ cells in the CS/asthma group was significantly higher than that in the other two groups. The total number of these cells in the CS/AR group was also higher than that in the CS only group The ratio of MBP+/GR+ cells to GR+ cells was highest in the CS/asthma group. The ratio of MBP+/GR+ cells to MBP+ cells in the CS only group was lower than those in the other two groups.

Expression of antiviral molecular genes in nasal polyp-derived cultured epithelial cells.

CONCLUSION: The results of the present study indicate the existence of natural immunity mechanisms via which viruses are eliminated from nasal and paranasal sinus mucosa. OBJECTIVES: Acute sinusitis and acute aggravation of chronic sinusitis are often caused by bacteria, which are secondary to viral infection of the nose. Antiviral molecules are considered to be expressed and protect the host after viral infection. We investigated the expression of antiviral molecules after viral infection of the nose. MATERIALS AND METHODS: We assessed the expression of antiviral molecules, defensin and interferon mRNA, by the real-time polymerase chain reaction (PCR) technique after stimulating cultured nasal polyp cells with polyinosine-polycytidylic acid (poly(I:C)), which is an analog of double-stranded (ds) RNA. RESULTS: The expression of beta-defensin mRNA significantly increased after the stimulation. On the other hand, expression of both interferon-alpha mRNA and interferon-beta mRNA was recognized, but only the expression of interferon-beta mRNA increased after the stimulation.

Double-stranded RNA poly(I:C) enhances matrix metalloproteinase mRNA expression in human nasal polyp epithelial cells.

CONCLUSION: The significant up-regulation of matrix metalloproteinase (MMP)-9 mRNA, which is not modulated by tissue inhibitor of metalloproteinase (TIMP)-1, is an additional source of increased proteolytic activity in virus-infected upper airways that might contribute to the exacerbation of chronic rhinosinusitis with nasal polyps. OBJECTIVES: Chronic rhinosinusitis is often exacerbated by viral infection. We hypothesized that a disruption of the mechanisms that regulate the activity of MMPs during viral infection is one possible mechanism responsible for the exacerbation. In the present study we attempted to achieve a better understanding of MMP expression in nasal epithelial cells after viral infection. MATERIALS AND METHODS: Human nasal epithelial cells were isolated from nasal polyp specimens obtained during endoscopic endonasal surgery in chronic rhinosinusitis patients. We investigated the expression of MMP-2, MMP-9, and TIMP-1 mRNA in primary human nasal polyp epithelial cells after dsRNA stimulation. RESULTS: Among the genes whose expression was evaluated, only expression of MMP-9 mRNA increased significantly after dsRNA stimulation.