Effectiveness of the analysis of craniofacial morphology and pharyngeal airway morphology in the treatment of children with obstructive sleep apnoea syndrome.

OBJECTIVE: In general, no consensus has been reached regarding the diagnostic criteria for obstructive sleep apnoea syndrome (OSAS) in children and the criteria for selecting treatment are inconsistent. Therefore, the craniofacial and pharyngeal airway morphology of OSAS in children who had undergone drug therapy (non-op group) and OSAS in children who had undergone both drug therapy and surgical therapy (adenotonsillectomy) (op group) were compared. The purpose of this study was to examine the effectiveness of craniofacial morphology and pharyngeal airway morphology analysis in the treatment of children with OSAS. METHODS: The craniofacial and pharyngeal airway morphology of the control group, the non-op group and the op group were compared to examine the differences of each group. The comparison used Mann-Whitney's U test. RESULTS: A comparison between the non-op and the op groups showed significant differences in the facial axis, mandibular plane angle, ramus plane to the SN (porion and orbit) point, point Pog (pogonion) to the McNamara line, anteroposterior dysplasia indicator (APDI), D-AD1 [the distance between the posterior nasal spine (PNS) point and the nearest adenoid tissue, measured along the PNS-Ba (basion) point plane], D-AD2 (the distance between the PNS point and the nearest adenoid tissue, measured along a line from the PNS point perpendicular to the S (sella turcica)-Ba point plane), upper pharynx and soft palatal length. The op group showed significantly lower values of APDI than the non-op group, indicating that the op group showed a significant occlusion of class II, and that the mandibular bone was positioned posteriorly relative to the maxillary bone. CONCLUSIONS: The op group showed a significant posterior position and backward rotation of the mandibular bone, stenosis of the nasopharyngeal airway and an elongated soft palate compared with the non-op group, and it was speculated that there was a high probability of the necessity of surgical therapy (adenotonsillectomy) when a morphological factor played a major role as a cause of obstructive sleep apnoea. We recommend craniofacial morphology analysis and pharyngeal airway morphology analysis in the diagnosis and treatment planning of OSAS children.

Actinohivin, a novel anti-HIV protein from an actinomycete that inhibits syncytium formation: isolation, characterization, and biological activities.

Blocking human immunodeficiency virus (HIV) entry into target cells is an important goal of HIV and acquired immune deficiency syndrome (AIDS) therapies. We have searched for anti-HIV substances from microorganisms using a syncytium formation assay system constructed with HeLa/CD4/Lac-Z and HeLa/T-env/Tat cells. We discovered a novel anti-HIV protein that inhibits syncytium formation, designated as actinohivin, from a cultured broth of a soil isolate, actinomycete strain K97-0003. ESI mass spectrometry of actinohivin isolated from the culture filtrate showed an ion with molecular mass of 12,520.3 Da. The amino acid sequence was determined by N-terminal Edman degradation of the intact protein and peptide fragments formed by endoproteinase digestions. Actinohivin consists of a 114-amino-acid chain that exhibits internal sequence triplication. Actinohivin inhibited both T-cell and macrophage tropic syncytium formation, with IC(50) values of 60 and 700 nM, respectively, and the cytopathic effect of HIV-1(IIIB) in MT-4 cells, with IC(50) value of 230 nM.

Health effects of fluoride pollution caused by coal burning.

Recently a huge amount of fluoride in coal has been released into indoor environments by the combustion of coal and fluoride pollution seems to be increasing in some rural areas in China. Combustion of coal and coal bricks is the primary source of gaseous and aerosol fluoride and these forms of fluoride can easily enter exposed food products and the human respiratory tract. Major human fluoride exposure was caused by consumption of fluoride contaminated food, such as corn, chilies and potatoes. For each diagnostic syndrome of dental fluorosis, a log-normal distribution was observed on the logarithm of urinary fluoride concentration in students in China. Urinary fluoride content was found to be a primary health indicator of the prevalence of dental fluorosis in the community. In the fluorosis areas, osteosclerosis in skeletal fluorosis patients was observed with a high prevalence. A biochemical marker of bone resorption, urinary deoxypyridinoline content was much higher in residents in China than in residents in Japan. It was suggested that bone resorption was stimulated to a greater extent in residents in China and fluoride may stimulate both bone resorption and bone formation. Renal function especially glomerular filtration rate was very sensitive to fluoride exposure. Inorganic phosphate concentrations in urine were significantly lower in the residents in fluorosis areas in China than in non-fluorosis area in China and Japan. Since airborne fluoride from the combustion of coal pollutes extensively both the living environment and food, it is necessary to reduce fluoride pollution caused by coal burning.

Neuroprotective effects of non-steroidal anti-inflammatory drugs by direct scavenging of nitric oxide radicals.

Recently, it has been reported that inflammatory processes are associated with the pathophysiology of Alzheimer's disease and that treatment of non-steroidal anti-inflammatory drugs reduce the risk for Alzheimer's disease. In the present study, we examined nitric oxide radical quenching activity of non-steroidal anti-inflammatory drugs and steroidal drugs using our established direct in vitro nitric oxide radical detecting system by electron spin resonance spectrometry. The non-steroidal anti-inflammatory drugs, aspirin, mefenamic acid, indomethacin and ketoprofen directly and dose-dependently scavenged generated nitric oxide radicals. In experiments of nitric oxide radical donor, NOC18-induced neuronal damage, these four non-steroidal drugs significantly prevented the NOC18-induced reduction of cell viability and apoptotic nuclear changes in neuronal cells without affecting the induction of inducible nitric oxide synthase-like immunoreactivity. However, ibuprofen, naproxen or steroidal drugs, which had less or no scavenging effects in vitro, showed almost no protective effects against NOC18-induced cell toxicity. These results suggest that the protective effects of the former four non-steroidal anti-inflammatory drugs against apoptosis might be mainly due to their direct nitric oxide radical scavenging activities in neuronal cells. These direct NO. quenching activities represent novel effects of non-steroidal anti-inflammatory drugs. Our findings identified novel pharmacological mechanisms of these drugs to exert not only their anti-inflammatory, analgesic, antipyretic activities but also neuroprotective activities against neurodegeneration.

Platinum(IV) complexes with dipeptide. X-ray crystal structure, 195Pt NMR spectra, and their inhibitory glucose metabolism activity in Candida albicans.

Three dipeptide complexes of the form K[Pt(IV)(dipep)Cl3] and two complexes of the form K[Pt(IV)(Hdipep)Cl4] were newly prepared and isolated. The platinum(IV) complexes containing the dipeptide were obtained directly by adding KI to H2[PtCl6] solution. The reaction using KI was rapidly completed and provided analytically pure yellow products in the form of K[Pt(dipeptide)Cl3] for H2digly, H2gly(alpha)-ala, H2alpha-alagly and H2di(alpha)-ala. The K[Pt(IV)(digly)Cl3] complex crystallizes in the monoclinic space group P2(1)/c with unit cell dimensions a = 10.540(3) A, b = 13.835(3) A, c = 8.123(3) A, beta = 97.01(2) degrees, Z = 4. The crystal data represented the first report of a Pt(IV) complex with a deprotonated peptide, and this complex has the rare iminol type diglycine(2-) coordinating to Pt(IV) with the bond lengths of the C2-N1 (amide) bond (1.285(13) A). The 195Pt NMR peaks of the K[Pt(IV)(dipep)Cl3] and the K[Pt(IV)(Hdipep)Cl4] complexes appeared at about 270 ppm and at about -130 ppm, respectively, and were predicted for a given set of ligand atoms. While the K[Pt(IV)(x-gly)Cl3] complexes, where x denotes the glycine or alpha-alanine moieties, were easily reduced to the corresponding platinum(II) complexes, the K[Pt(IV)(x-alpha-ala)Cl3] complexes were not reduced, but the Cl- ion was substituted for OH- ion in the reaction solution. The K[Pt(digly)Cl3] and K[Pt(gly-L-alpha-ala)Cl3] complexes inhibited the growth of Candida albicans, and the antifungal activities were 3- to 4-fold higher than those of cisplatin. The metabolism of glucose in C. albicans was strongly inhibited by K[Pt(digly)Cl3] and K[Pt(gly-L-alpha-ala)Cl3] but not by the antifungal agent fluconazole.

Molecular cloning of actinohivin, a novel anti-HIV protein from an actinomycete, and its expression in Escherichia coli.

Syncytium-inducing variants of the HIV-1 virus are correlated with poor diagnosis and rapid disease progression. We have recently discovered a novel anti-HIV protein, referred to as actinohivin, that inhibits syncytium formation. Here we describe the cloning and sequencing of the gene encoding actinohivin from the actinomycete strain K97-0003, and its expression in Escherichia coli. The actinohivin gene was located on a 0.8-kb BamHI fragment of genomic DNA. The fragment contained an open reading frame of 480 bp, which encoded a protein of 160 amino acids with calculated molecular weight of 17492.7. The N-terminal region was found to be a typical signal peptide of prokaryotes, and actinohivin was located at amino acid positions 46-160. The actinohivin gene could be expressed in E. coli using a pET30Xa/LIC expression vector and the purified recombinant actinohivin was found to inhibit syncytium formation to a similar extent as actinohivin from its natural source.

A simple screening system for anti-HIV drugs: syncytium formation assay using T-cell line tropic and macrophage tropic HIV env expressing cell lines--establishment and validation.

The first step in cellular entry of HIV involves binding of the viral envelope glycoprotein complex (gp120/gp41) to specific receptor molecules on the target cells. The cell-cell fusion (syncytium formation) between env expressing cells and CD4+ cells mimics the viral infection of the host cells. To search for anti-HIV substances preventing this process, we constructed the recombinant cell lines, HeLa/CD4/Lac-Z and HeLa/T-env/Tat for T-cell tropic (HIV-1(NL4-3)) system, and HOS/CD4/CCR5/Lac-Z and HeLa/M-env/Tat for macrophage tropic (HIV-1(SF162)) system. When each pair of cells were co-incubated for 20 hours, the multinuclear giant cells (syncytia) were formed and beta-galactosidase was expressed. These systems are less biohazardous because no infectious virus particles are used. Their validity in screening for anti-HIV substances which inhibit syncytium formation was confirmed using various known HIV entry inhibitors.

Nitric oxide modulates muscarinic acetylcholine receptor binding in the cerebral cortex of gerbils.

To determine whether nitric oxide (NO) acts as a modulator of muscarinic acetylcholine receptor (mACh-R) function, we performed a radioligand receptor assay using [3H]quinuclidinyl benzylate ([3H]QNB), the NO radical (NO*) donor 3-(2-Hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamin e (NOC7) and a gerbil brain cortical membrane preparation. NOC7 (at 10 microM, 100 microM or 1 mM concentrations) significantly reduced the [3H]QNB binding Kd values (from 0.196 +/- 0.009 nM in the control, to 0.151 +/- 0.013, 0.144 +/- 0.012 and 0.153 +/- 0.007 nM respectively). NOC7 did not alter the displacement curves of atropine or carbachol. Reduction of SH groups with dithiothreitol, in the presence of the NO donor, significantly increased [3H]QNB binding affinity whereas alkylation by N-ethylmaleimide markedly decreased it. The observed enhancing effect on mACh-R binding affinity for [3H]QNB, may reflect conformational changes in the receptors mediated by the NO generated, and these changes might be explained by NO reactions with such groups through conditions supporting redox reactions intrinsic to the NO molecule, similar to those occurring in redox regulatory sites reported for other neurotransmitter pathways in the CNS.

Pergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and inhibits lipid peroxidation in different regions of the rat brain.

The free radical hypothesis for the pathogenesis and/or progression of Parkinson's disease (PD) has gained wide acceptance in recent years. Although it is clear that dopamine (DA) agonists cannot completely replace levodopa therapy, they can be beneficial early in the course of PD by reducing the accumulation of DA which undergoes auto-oxidation and generates cytotoxic free radicals. In the present study we demonstrate that pergolide, a widely used DA agonist, has free radical scavenging and antioxidant activities. Using a direct detection system for nitric oxide radical (NO.) by electron spin resonance (ESR) spectrometry in an in vitro .NO-generating system, we examined the quenching effects of pergolide on the amount of NO. generated. Pergolide dose-dependently scavenged NO.. In the competition assay, the IC50 value for pergolide was estimated to be about 30 microM. Pergolide also dose-dependently attenuated the hydroxyl radical (.OH) signal in an in vitro FeSO4-H2O2 ESR system with an approximate IC50 value of 300 microM. Furthermore, this agent significantly inhibited phospholipid peroxidation of rat brain homogenates in in vitro experiments and after repeated administration (0.5 mg/kg/24 h, i.p. for 7 days). Our findings suggest a neuroprotective role for pergolide on dopaminergic neurons due to its free radical scavenging and antioxidant properties.

Effects of repeated cyclosporin A administration on iminodipropionitrile-induced dyskinesia and TRE-/CRE-binding activities in rat brain.

To clarify the involvement of immunophilin ligands in the pathogenesis and pathophysiology of dyskinesia, we examined the effects of repeated administration of cyclosporin A (CsA) on rat dyskinesia induced by repeated injection of iminodipropionitrile (IDPN 100 mg/kg, i.p., for 7 days). The addition of CsA treatment (5 mg/kg, s.c., 1 h before each IDPN injection) exacerbated IDPN-induced dyskinesia. In the group treated with both CsA and IDPN, the concentration of dopamine was significantly increased in the striatum and nucleus accumbens compared with the group treated with IDPN alone. Furthermore, in the electrophoretic mobility shift assay, the injection of CsA + IDPN increased binding activities of transcription factors to the TPA (12-O-tetradecanoylphorbol-13-acetate)-responsive element (TRE) and to the cAMP response element (CRE) in the striatum and nucleus accumbens, compared with those in rats treated with IDPN alone. The levels of D1-receptor mRNA in the striatum were significantly decreased in the IDPN-treated rats but were at the control level in the rats given CsA + IDPN. These findings suggest that the behavioral aggravation of the IDPN-induced dyskinesia caused by CsA administration may be due to the acceleration of the pre- and post-synaptic dopaminegic systems via activation of transcription factors which bind upstream to tyrosine hydroxylase and D1-receptor genes, and that the immunophilin binding agents such as CsA are involved in this aggravated dyskinesia.

Health effects of indoor fluoride pollution from coal burning in China.

The combustion of high fluoride-content coal as an energy resource for heating, cooking, and food drying is a major exhaust emission source of suspended particulate matter and fluoride. High concentrations of these pollutants have been observed in indoor air of coal-burning families in some rural areas in China. Because airborne fluoride has serious toxicological properties, fluoride pollution in indoor air and the prevalence of fluorosis have been analyzed in a fluorosis area and a healthy nonfluorosis area in China and in a rural area in Japan. For human health, fluoride in indoor air has not only been directly inhaled by residents but also has been absorbed in stored food such as corn, chilies, and potatoes. In the fluorosis area in China, concentrations of urinary fluoride in the residents have been much higher than in the nonfluorosis area in China and in the rural area in Japan. In the fluorosis area, almost all elementary and junior high school students 10-15 years of age had dental fluorosis. Osteosclerosis in the skeletal fluorosis patients was very serious. Urinary deoxypyridinoline in rural residents in China was much higher than in rural residents in Japan. Data suggest that bone resorption was extremely stimulated in the residents in China and that fluoride may stimulate both bone resorption and bone formation. Because indoor fluoride from combustion of coal is easily absorbed in stored food and because food consumption is a main source of fluoride exposure, it is necessary to reduce airborne fluoride and food contamination to prevent serious fluorosis in China.

Age-related effects of heat stress on protective enzymes for peroxides and microsomal monooxygenase in rat liver.

To evaluate the age-related response of essential cell functions against peroxidative damage in hyperthermia, we studied the biochemical response to heat stress in both young and aged rats. Passive hyperthermia was immediately observed in rats after exposure to hot environments. In aged rats, the rectal temperature maintained thermal homeostasis and increased to the same degree as in young rats. In these aged animals, the damage from heat stress was more serious than in young animals. In aged rats under normal environmental conditions, hepatic cytosolic glutathione peroxidase (GSH peroxidase) activities were markedly higher than those activities in younger rats. Hepatic cytosolic GSH peroxidase activities were induced by heat stress in young rats but were decreased by hot environments in aged rats. Hepatic catalase activities in young rats were not affected by hot environments, whereas in aged rats, hepatic catalase activities were seriously decreased. Catalase activities in the kidney of aged rats were also reduced by hot environments. Lipid peroxidation in the liver was markedly induced in both young and aged rats. Because the protective enzymes for oxygen radicals in aged rats were decreased by hot environments, lipid peroxidation in the liver was highly induced. In aged rats, lipid peroxidation in intracellular structures such as mitochondria and microsomes was also markedly induced by hot environments. In both young and aged rats, hyperthermia greatly increased the development of hypertrophy and vacuolated degeneration in hepatic cells. In aged rats, both mitochondria and endoplasmic reticulum of the hepatic cells showed serious distortion in shape as a result of exposures to hot environments. Microsomal electron transport systems, such as cytochrome P450 monooxygenase activities, were seriously decreased by heat stress in aged rats but not in young rats. Although the mitochondrial electron transport systems were not affected by acute heat stress in young rats, their activities were simultaneously inhibited after long-lasting heat exposure. In isolated hepatic cells and polymorphonuclear leukocytes in animals, the 70-kDa heat shock-induced proteins were markedly increased by heat stress. In conclusion, the heat stress-inducible oxygen radical damage becomes more severe according to the age of rats. Because aging and hyperthermia have a synergistic effect on lipid peroxidation, protective enzyme activities for oxygen radicals may be essential for surviving and recovering from thermal injury in aged animals and also in humans.

[Endemic fluorosis in southern China: radiological findings].

Fluorosis continues to be prevalent in the southern regions of China. The endemic fluorosis caused by inhalation of fluoride-containing coal dust etiologically contrasts with the common occurrence of endemic fluorosis due to the intake of fluoride-containing water. We investigated the radiologic findings in 49 affected individuals in a district of this region. More than 80% of patients exhibited radiologic evidence of skeletal fluorosis, and most patients belonged to stage 3 of Singh and Jolly's classification. The most common skeletal abnormality was ossification of the interosseous ligaments in the extremities, which warranted radiographic examination of the limbs as a tool for screening.

Ketoprofen, a non-steroidal anti-inflammatory drug prevents the late-onset reduction of muscarinic receptors in gerbil hippocampus after transient forebrain ischemia.

Ischemia-induced hippocampal late-onset reduction of muscarinic acetylcholine receptors (LORMAR) begins as late as 7 days after transient forebrain ischemia in the gerbil, but it precedes to completion of neuronal death in the CA1 region. We previously reported that post-ischemic administration of cyclosporin A prevented LORMAR with suppression of astroglial and microglial activation. In the present study, we showed that the chronic post-ischemic administration of a non-steroidal anti-inflammatory drug, ketoprofen (5 mg/kg, subcutaneously, twice a day for 14 days) significantly reduced LORMAR both 14 days and 21 days after 5-min transient ischemia. This protective effect of ketoprofen against LORMAR suggests that the non-steroidal anti-inflammatory drugs is clinically efficacious in the treatment of LORMAR, a sequela of cerebral ischemia.