Increased phosphatidylcholine concentration in saliva reduces surface tension and improves airway patency in obstructive sleep apnoea.

Surface tension may have important role for maintaining upper airway patency in patients with obstructive sleep apnoea. It has been demonstrated that elevated surface tension increases the pharyngeal pressures required to reopen the upper airway following collapse. The aim of the study was to evaluate the associations between the concentrations of endogenous surfactants in saliva with indices of upper airway patency in obstructive sleep apnoea. We studied 20 male patients with obstructive sleep apnoea (age: 60·3 ± 10·3 years; BMI: 25·9 ± 4·6 kg m(-2); AHI: 41·5 ± 18·6 events h(-1)). We obtained 100-µL samples of saliva prior to overnight polysomnographic sleep study. The surface tension was determined using the pull-off force technique. The concentration of phosphatidylcholine (PC) was evaluated by liquid chromatography-mass spectrometry (LC-MS/MS). Regression analysis between apnoea, hypopnoea and apnoea/hypopnoea indices and the ratio of hypopnoea time/total disordered breathing time (HT/DBT) with surface tension and PC were performed. P < 0·05 was considered significant. The mean saliva surface tension was 48·8 ± 8·0 mN m(-1) and PC concentration was 15·7 ± 11·1 nM. The surface tension was negatively correlated with the PC concentration (r = -0·48, P = 0·03). There was a significant positive correlation between surface tension with hypopnoea index (r = 0·50, P = 0·03) and HT/DBT (r = 0·6, P = 0·006), but not apnoea or apnoea/hypopnoea index (P > 0·11). Similarly, PC concentration negatively correlated with hypopnoea index (r = -0·45, P = 0·04) and HT/DBT (r = -0·6, P = 0·004), but not with apnoea index or AHI (P > 0·08). An increase in salivary PC concentration may increase upper airway patency in obstructive sleep apnoea through a reduction in surface tension.

Range of motion exercise of temporo-mandibular joint with hot pack increases occlusal force in patients with Duchenne muscular dystrophy.

The purpose of this study is to evaluate whether the range of motion exercise of the temporo-mandibular joint (jaw ROM exercise) with a hot pack and massage of the masseter muscle improve biting disorder in Duchenne muscular dystrophy (DMD). The subjects were 18 DMD patients (21.3+/- 4.1 years old). The jaw ROM exercise consisted of therapist-assisted training (2 times a week) and self-training (before each meal every day). The therapist-assisted training consisted of the application of a hot pack on the cheek of the masseter muscle region (15 minutes), the massage of the masseter (10 minutes), and jaw ROM exercise (5 minutes). The self-training involved jaw ROM exercise by opening the mouth to the maximum degree, ten times. These trainings continued for six months. Outcomes were evaluated by measuring the greatest occlusal force and the distance at the maximum degree of mouth opening between an incisor of the top and that of the bottom. Six months later, the greatest occlusal force had increased significantly compared with that at the start of jaw ROM exercise (intermediate values: from 73.8N to 97.3N) (p = 0.005) as determined by the Friedman test and Scheffi's nonparametric test. The patients' satisfaction with meals increased. However, the maximum degree of mouth opening did not change after six months of jaw ROM exercise. Jaw ROM exercise in DMD is effective for increasing the greatest occlusal force.

The development of the hypothalamus-pituitary-adrenal axis during infancy may be affected by antenatal glucocorticoid therapy.

BACKGROUND: Developmental changes in the hypothalamus-pituitary-adrenal (HPA) axis during infancy have been reported in term infants, but those in preterm infants have yet to be elucidated. If developmental changes in the HPA axis of preterm infants are modulated by any factors, it may affect their future health. Few studies have examined the lasting consequences of antenatal glucocorticoids on the development of the HPA axis. METHODS: We measured pre- and post-palivizumab vaccination salivary cortisol values in two conforming periods of three-months intervals during infancy, and compared cortisol values and the response of cortisol secretion between groups with and without antenatal glucocorticoid (AG) therapy. RESULTS: Although the strength of the response of cortisol secretion to palivizumab fell age-dependently (until late infancy) in the Non-AG group, the opposite pattern was exhibited in the AG group. The changes of the delta cortisol values between the 2 groups were significant. CONCLUSIONS: This study suggests that the HPA axis of preterm infants whose mothers receive AG therapy may be upregulated during infancy, possibly leading to long lasting health problems.

Changes in surface tension of saliva in Down syndrome.

OBJECTIVE: Surface tension in saliva might contribute to the maintenance of upper airway patency. The present study aimed to determine whether salivary surface tension is altered in patients with Down syndrome who are predisposed to upper airway collapse. PATIENTS AND METHODS: We used the pull-off force technique to measure surface tension in samples (100 µL) of saliva collected from twenty-three male patients with Down syndrome and twenty-three healthy males (controls). p < 0.05 was considered to indicate significance. RESULTS: Salivary surface tension was significantly lower in the patients than in the controls (57.3 ± 4.9 vs. 60.3 ± 4.7 mN/m; p = 0.039). Age and surface tension positively correlated in the patients (p = 0.001). CONCLUSIONS: The lower surface tension of saliva in patients with Down syndrome might compensate for an anatomical predisposition towards upper airway collapsibility and other risk factors. The function of surface tension in saliva might be altered due to aging in such patients.

Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models.

BACKGROUND: This study aimed to examine the effects of Lactobacillus casei strain Shirota (LcS) on gut-brain interactions under stressful conditions. METHODS: Three double-blind, placebo-controlled trials were conducted to examine the effects of LcS on psychological and physiological stress responses in healthy medical students under academic examination stress. Subjects received LcS-fermented milk or placebo daily for 8 weeks prior to taking a national standardized examination. Subjective anxiety scores, salivary cortisol levels, and the presence of physical symptoms during the intervention were pooled and analyzed. In the animal study, rats were given feed with or without LcS for 2 weeks, then submitted to water avoidance stress (WAS). Plasma corticosterone concentration and the expression of cFos and corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN) were measured immediately after WAS. In an electrophysiological study, gastric vagal afferent nerve activity was monitored after intragastric administration of LcS to urethane-anesthetized rats. KEY RESULTS: Academic stress-induced increases in salivary cortisol levels and the incidence rate of physical symptoms were significantly suppressed in the LcS group compared with the placebo group. In rats pretreated with LcS, WAS-induced increases in plasma corticosterone were significantly suppressed, and the number of CRF-expressing cells in the PVN was reduced. Intragastric administration of LcS stimulated gastric vagal afferent activity in a dose-dependent manner. CONCLUSIONS & INFERENCES: These findings suggest that LcS may prevent hypersecretion of cortisol and physical symptoms under stressful conditions, possibly through vagal afferent signaling to the brain and reduced stress reactivity in the PVN.

Effect of serum protein binding on real-time trafficking of liposomes with different charges analyzed by positron emission tomography.

Liposomes have been used as carriers of various materials and as tools for gene transfer: for the latter purpose, positively charged liposomes are usually used. To evaluate the stability in the presence of serum and the in vivo behavior of such liposomes as well as those aspects of neutral and negatively charged liposomes, we investigated liposomal agglutinability in the presence of serum, serum protein binding to these liposomes, and real-time liposomal trafficking by a non-invasive method using positron emission tomography (PET). Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol without or with charged lipid were prepared in the presence of mannitol, and the turbidity change in the presence of serum was determined. Turbidity increase was not observed for so-called long-circulating liposomes, i.e., liposomes modified with glucuronic acid or with poly(ethylene glycol), or for negatively charged liposomes containing dicetyl phosphate (DCP), phosphatidylglycerol, or phosphatidylserine. On the contrary, a significant turbidity increase was observed when positively charged liposomes modified with stearylamine, stearyltrimethylammonium chloride or 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl bromide (DMRIE), which is known as a component of liposomes for gene transfer, were used. These liposomes were found to have bound a high amount of serum proteins after separation of unbound serum proteins by use of a spin column. The liposomal trafficking in vivo was determined for three kinds of liposomes, i.e., liposomes with DMRIE, those with DCP, and those without charged lipids. These liposomes were prepared in the presence of 2-[18F]fluoro-2-deoxy-D-glucose ([2-18F]FDG), and the [2-18F]FDG-labeled liposomes were administered to mice to perform PET scans. Positively charged liposomes containing DMRIE showed high accumulation in the liver compared with neutral and negatively charged liposomes. Since DMRIE-liposomes tended to aggregate in the presence of serum, and to be associated with serum protein, these characteristics may lead to the high uptake of DMRIE-liposomes by the liver.

Age-related discontinuous changes in the in vivo fluorescence of human facial skin.

We measured the 325-nm laser-induced fluorescence of the skin of the face and ventral forearm in seventy Japanese female volunteers, and evaluated the effects of age and exposure to sunlight. The subjects were arbitrarily grouped into 10-year age-groups. In slightly exposed areas such as the ventral forearm, the average laser-induced intensity ratio at 390 nm to 430 nm showed no significant differences with the age group. In areas markedly exposed to sunlight such as the corners of the eyes and mouth, the average laser-induced intensity ratio showed a discontinuous decrease with age. These findings suggested that dermal fluorophore changes differ with the skin areas and are affected by sunlight exposure.

[Juvenile parkinsonism with symmetrical hypoperfusion in the cerebellum--a case report].

We report a 24-year-old female presenting levodopa-responsive juvenile parkinsonism with symmetrical hypoperfusion in the cerebellum. At the age of 21, she noticed difficulty in brushing her teeth and writing with the right hand. She developed resting tremor in the right hand. These symptoms were dramatically relieved by levodopa. One year prior to the admission, she noticed dystonia and drug-induced motor fluctuations and her symptoms became worse. Neurological examinations disclosed resting and postural tremor in both hands and the right leg. Bradykinesia and cogwheel rigidity were noted on the right side. Deep tendon reflexes were slightly increased on the right side, while Babinski sign was negative. Slight lateropulsion was observed without retropulsion. Sensory, autonomic and cerebellar disturbances were not observed. No abnormalities were found in parkins gene or in the genes of spinocerebellar ataxia (SCA) 1,2,3,6,7,8 and alpha-synuclein. Cranial CT scan and brain MRI were normal, but technetium-99m ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) showed symmetrical hypoperfusion in the cerebellum. Other 5 patients presenting juvenile parkinsonism and 10 aged-matched normal controls in our hospital did not show hypoperfusion in the cerebellum on ECD SPECT. Cerebellar blood flow has not been measured in the previously reported cases of juvenile parkinsonism. These results suggested that etiopathogenesis in this patient was different from that in previously reported cases.

[Beneficial effect of eyelid make-up (natural rubber latex) to induce a new fold in the treatment of blepharoptosis in myotonic dystrophy].

Blepharoptosis is one of the troublesome ocular complications of myotonic dystrophy. To correct drooping eyelids for two men with myotonic dystrophy, we used Eye Putti, a cosmetic made of natural rubber latex, which induces a new fold in the upper eyelid. The cosmetic rubber latex dramatically improved the sight of a 59-year-old patient who previously had a great difficulty in looking forward and had to bend his head backward to see an object because of severe blepharoptosis. The other patient aged 54 with moderate ptosis also had satisfactory improvement. Appropriate use did not prevent eye blinking and induce corneal erosion or skin rash. The cosmetic rubber latex was effective to patients who had no residual function of the levator palpebrae and frontal muscles. This daily treatment is simple and safe, therefore may have an advantage over surgical correction of blepharoptosis for patients not only with myotonic dystrophy, but with other neuromuscular disorders including oculopharyngeal muscular dystrophy.

The type A behavior pattern and immune reactivity to brief stress: change of volume of secretory immunoglobulin A in saliva.

This article presents findings of a laboratory experiment on the association of the Type A behavior pattern with reactivity of secretory immune functioning to brief stress. 38 female undergraduate students classified as Type A (n = 19) or as Type B (n = 19) on the basis of their scores on the Kwansei Gakuin Type A scale performed a continuous arithmetic task in a situation in which they were exposed to aversive loud noise. Secretory immunoglobulin A (s-IgA) in saliva and autonomic measures (heart rate and frequency of eyeblink) were evaluated before and after the manipulation of stress. The volume of s-IgA at baseline was significantly higher for the Type A group than for the Type B group, suggesting that the former relative to the latter might be chronically higher in mucosal immune functioning. Also, the volume of s-IgA significantly increased after exposure to a brief stress for the Type B group but did not change for the Type A group, a finding which might indicate that the Type A group may have less immune reactivity to a brief stress.

Temperature change does not affect force between single actin filaments and HMM from rabbit muscles.

The temperature dependence of sliding force, velocity, and unbinding force was studied on actin filaments when they were placed on heavy meromyosin (HMM) attached to a glass surface. A fluorescently labeled actin filament was attached to the gelsolin-coated surface of a 1-microm polystyrene bead. The bead was trapped by optical tweezers, and HMM-actin interaction was performed at 20-35 degrees C to examine whether force is altered by the temperature change. Our experiments demonstrate that sliding force increased moderately with temperature (Q(10) = 1.6 +/- 0.2, +/-SEM, n = 9), whereas the velocity increased significantly (Q(10) = 2.9 +/- 0.4, n = 10). The moderate increase in force is caused by the increased number of available cross-bridges for actin interaction, because the cross-bridge number similarly increased with temperature (Q(10) = 1. 5 +/- 0.2, n = 3) when measured during rigor induction. We further found that unbinding force measured during the rigor condition did not differ with temperature. These results indicate that the amount of force each cross-bridge generates is fixed, and it does not change with temperature. We found that the above generalization was not modified in the presence of 1 mM MgADP or 8 mM phosphate.

Modified sagittal split ramus osteotomy with a reciprocating saw and new retractors.

Modified sagittal split ramus osteotomy with new instruments and a reciprocating saw is reported. With this modification, the sagittal separation of the ramus is performed by the reciprocating saw with an original wide-blade buccal retractor and a new lingual retractor, instead of the traditional channeled retractor. The wide-blade retractor is inserted to the buccal aspect of the mandibular ramus, which ensures protection from instrumental injury to the adjacent soft tissues and vessels, and the new lingual retractor, instead of the channeled retractor, is inserted to the lingual aspect of the ramus. The osteotomy line follows that of Dal Pont's modification. Close attention must be paid to the direction of the saw blade. The separated bone plane should be located in the external cortical bone layer of the ramus, so as to avoid injury of the inferior alveolar neurovascular bundle. The osteotomy is completed with the smooth osteotomized interface, which facilitates positioning of the bone segments by the surgeon. The new instruments and the reciprocating saw may provide safe and rapid sagittal split ramus osteotomy.

Home lead-work as a potential source of lead exposure for children.

Health examinations for lead poisoning were made on 62 family members from 15 families of homes carrying on lead work, such as quench-hardening in a molten lead bath and type-printing, as work at home. The most interesting findings concern the occurrence of cases with an unduly high lead absorption among children, but not among adult family members other than home lead-workers. The home environments of the children with an unduly high lead absorption represented contamination with housedust high in lead contents. The ingestion of the contaminated housedust by hand-to-mouth is probably responsible for the excessive lead exposure of the affected children. The results of the present study suggest that contamination of housedust with lead due to home lead-work constitutes a possible hazardous source of lead exposure for children.

[A case of chronic aspiration pneumonia after total gastrectomy caused by gastroesophageal reflux revealed by a "modified-salivagram"].

A 76-year-old male patient suffered from recurrent bacterial pneumonia of the right upper lobe and both lower lobes since 2 years after total gastrectomy for gastric cancer. He was treated with antibiotics repeatedly without complete remission. Meanwhile, chronic cough, purulent sputum, and persistent bilateral pulmonary infiltration developed gradually. Upper digestive tract endoscopy showed moderate reflux esophagitis. For diagnosis, we performed upper digestive tract scintigraphy, a "modified-salivagram", to detect aspiration and GER. Although aspiration was not detected, GER reaching to the upper portion of the esophagus was observed 46 min after taking radio-labeled albumin, and chronic aspiration pneumonia with GER was thus diagnosed. Bed blocks and gragling with ponvidone-iodine after meals and before sleep greatly improved the symptoms of cough and sputum. The bilateral infiltrative shadows disappeared with resolution of symptoms. Chronic aspiration resulting from GER is an important cause of chronic airway infection. Even if a patient with reflux esophagitis is asymptomatic, chronic aspiration pneumonia should be suspected in cases of recurrent or persistent pneumonia in both lower lobes. The "modified-salivagram" is a sensitive test to detect aspiration and GER in hypoacidic states, such as in total gastrectomy and elderly patients.

[Orthodontic uprighting mandibular second molars].

Two cases of impaction of the mandibular second molar treated by means of orthodontic techniques, were presented. It takes about 6 to 8 months for uprighting mandibular second molar. There is no significant difference in the uprighting times between in the case of extraction of the third molar or not. We consider that the corticotomy of the diatal part of the mandibular second molar shortens the uprighting times of the mandibular second molar. Treatment results of both cases were favorable at 2 years after uprighting of the mandibular second molar.

[Comparisons of effects of vitamin D3 metabolites on mineralization: utilization of incisor dentin in parathyroidectomized rats].

The rat incisor is continuously growing throughout the animal's life recording the state of mineralization within its dentin at all times. Therefore, it was assumed that the incisor dentin was suitable material for studying the effects of various drugs on such mineralization. The present study set out to examine the effects of vitamin D3 metabolites on the remineralization of dentin and the serum calcium level in parathyroidectomized (PTX) rats. Male Wistar rats weighing about 200-250 g were parathyroidectomized. Each rat was given daily 12 g of a synthetic diet containing 0.1% Ca and 0.4% P (normal P) or 0.06% P (P deficient) without vitamin D. Exp. I: Three groups of rats given a normal P diet were orally administered vehicle, 25 (OH) D3 (50 IU/rat) or 1,25 (OH)2D3 (5 IU/rat) for 5 days from the 28th day after PTX, respectively. Exp. II: Two groups of rats given a normal P diet or a P deficient diet were further divided into 4 sub-groups and intramuscularly administered 0, 5,000, 10,000 or 20,000 IU of vitamin D3 on the 9th day after PTX, respectively. The active vitamin D3, 1,25 (OH)2D3 restored the mineralization of the dentin which had been suppressed following PTX, and elevated the serum calcium level to about 9 mg/dl. However, the 25 (OH) D3 neither restored the mineralization of the dentin nor elevated the serum calcium level in the PTX rats. At doses below 1,000 IU, vitamin D3 could not restore the mineralization of the dentin. However, at massive doses above 5,000 IU, the mineralization was restored in proportion to the dose. The serum calcium levels also increased in proportion to the dose. It is assumed that the increase of the serum calcium level was mainly due to the enhancement of calcium absorption from the intestine by vitamin D3. Both remineralization of the incisor dentin and increase of the serum calcium level were more marked in groups of rats given a P deficient diet than in those given a normal P diet. In all cases in the present experiments, the degree of mineralization of the dentin seemed to correspond with the degree of elevation of the serum calcium levels. These results suggest that the remineralization of the dentin in the PTX rats was attributable to the effect of the vitamin D3 metabolites on serum calcium regulation. Relative biological activities of 1,25 (OH)2D3, 25 (OH) D3 and vitamin D3 on the remineralization of dentin were estimated to be 1, less than 0.02 and less than 0.001, respectively.

Epidermolysis bullosa simplex associated with muscular dystrophy: phenotype-genotype correlations and review of the literature.

BACKGROUND: Epidermolysis bullosa simplex associated with muscular dystrophy (EBS-MD; OMIM# 226670) is an autosomal recessive disorder caused by genetic defects in the plectin gene. Because EBS-MD is relatively rare, and gene defects have been elucidated only in a limited number of patients, the precise phenotype-genotype correlations have not yet been fully elucidated. OBJECTIVE: The purpose of this study was to define clinical features of EBS-MD and to clarify its phenotype-genotype correlations. METHODS: Clinical, ultrastructural, immunohistochemical, and molecular features of 4 unrelated Japanese patients with EBS-MD were recorded. In addition, 6 cases with defined plectin gene mutations reported in the literature were reviewed. RESULTS: In skin of the EBS-MD patients, the blister formation always occurs just above the hemidesmosomes, and expression of plectin is absent or markedly reduced in all cases examined. All 10 patients, including 6 cases in the literature, showed generalized blistering at birth or soon thereafter, and experienced nail deformities. In addition, decayed teeth (5 cases), urethral strictures (3), mild palmoplantar hyperkeratosis (2), infantile respiratory complications (2), alopecia (1), and laryngeal webs (1) were present. All 8 patients who were older than 9 years demonstrated considerable muscle weakness, and the majority of them ended up being wheelchair bound. Among the 10 patients, 7 were products of consanguineous marriage, 9 have premature termination codon (PTC) mutations in both alleles of the plectin gene, and 7 cases were homozygous for the mutation. One patient who is homozygous for a 2719del9 in-frame deletion mutation that resulted in elimination of 3 amino acids, QEA, could still walk at the age of 46 and showed milder clinical severity. CONCLUSION: EBS-MD reveals clinical features not only characteristic of EBS and MD, but also other manifestations including urethral, dental, and respiratory complications. The majority of patients are products of consanguineous marriage and have homozygous plectin gene mutations. Whereas patients with PTC mutations in both alleles typically showed severe clinical features of EBS-MD and ended up being wheelchair bound, a homozygous patient for an in-frame deletion mutation showed positive, yet attenuated, plectin expression and milder clinical phenotype. Thus plectin immunofluorescence, combined with identification of the underlying plectin mutations, is of value in predicting the severity of the muscle involvement that occurs later in life of patients with EBS-MD.