Photobiomodulation increases uprighting tooth movement and modulates IL-1ß expression during orthodontically bone remodeling.

This study investigated the effects of photobiomodulation (PBM) in acceleration of orthodontic movement of inferior molar uprighting movement. Thirty-four individuals, with indication of molar uprighting movement for oral rehabilitation, were randomly divided in two groups: verticalization + PBM (808 nm, 100 mW, 1 J per point, 10 points and 25 J/cm2 ) or verticalization + PBM simulation. Elastomeric chain ligatures were changed every 30 days for 3 months. FBM was performed immediately, 24 h, 72 h, 1 and 2 months after activation. The primary outcome was the amount of uprighting movement. Secondary outcomes were pain, amount of medication, OHIP-14 questionnaire, and cytokine IL-1ß. PBM group increase uprighting movement when compared to control after 3 months and modulate IL-1ß expression. For pain control, the amount of medication and OHIP-14 no difference were found. This study suggests that PBM accelerates tooth movement during molar uprighting, due to modulation of IL-1ß during bone remodeling.

Evaluation of the effects of photobiomodulation on orthodontic movement of molar verticalization with mini-implant: A randomized double-blind protocol study.

INTRODUCTION: Loss of a dental element can generate several repercussions in the stomatognathic system. According to the latest survey by the Ministry of Health, in 2010, Brazilian adults had, on average, 7 missing teeth. This loss may lead to movement of the adjacent teeth and the antagonist, which would make prosthetic rehabilitation harder to do. Anchoring systems, such as mini-implants, have been increasingly used as a treatment option because they act with heavy but controlled forces and without side effects. Recent studies have shown that photobiomodulation (PBM) can accelerate orthodontic movement in molar intrusion. The objective of this study will be to evaluate the effect of PBM on the acceleration of the orthodontic movement of molar verticalization and its effect on pain and inflammation of the periodontal tissues. PATIENT CONCERNS:: the concerns assessments will be done over the study using anamnesis interviews and specific questionnaire. DIAGNOSIS: verticalization will be evaluated by clinical and radiographic analysis. INTERVENTIONS: Thirty four healthy patients aged 30 to 60 years, who need to recover the prosthetic space for oral rehabilitation after loss of the posterior inferior dental elements and inclination of the adjacent element, will be randomly divided into 2 groups: G1 (control group) - verticalization by mini-implant + PBM simulation (placebo); G2 (experimental group) - verticalization by mini-implant + PBM. The movements will occur with the aid of mini-implants and elastomeric chains ligatures. The PBM will occur with diode laser application, 808 nm, 100 mW, receiving 1J per point, 10 seconds, 10 points (5 per buccal and 5 per lingual) and radiant exposure of 25 J/cm. The orthodontic forces of verticalization (corresponding to any exchange of elastomeric ligation) will be applied every 30 days and the PBM will be applied immediately, 3 and 7 days of each month, for a period of 3 months. The crevicular gingival fluid (CGF) will be collected on the 1st, 3rd, and 7th days after the first activation, and then on the 3rd day of the following 2 months. OUTCOMES: Interleukins IL1ß, IL-6, IL-8, IL-10, and TNF-α will be analyzed by ELISA. Panoramic radiography will be performed at baseline and 90 afterwards to ascertain the amount (in degrees) of verticalization. To evaluate the pain, the Visual Analog Scale (VAS) will be used in all the consultations, and to evaluate the quality of life, the Oral Health Impact Profile (OHIP-14) questionnaire will be applied. Analgesics will be given and the quantity of drugs will be counted. If the data are normal, they will be submitted to Student t test. The data will be presented as means ± SD and the value of p will be defined as <0.05. DISCUSSION: This protocol will determine the effectiveness of photobiomoduation regarding the orthodontic movement of molar verticalization. ETHICS AND DISSEMINATION: This protocol received approval from the Human Research Ethics Committee of Universidade Nove de Julho (certificate number: 3 533 219). The data will be published in a peer-reviewed periodical.

Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies.

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human malignancy. An internal tandem duplication (ITD) of the juxtamembrane (JM) domain-coding sequence of the FLT3 gene (FLT3/ITD) is found in 20% of patients with acute myeloid leukemia (AML) and is strongly associated with leukocytosis and a poor prognosis. On the other hand, mutations of the c-KIT gene, which have been found in mast cell leukemia and AML, are clustered in 2 distinct regions, the JM domain and D816 within the activation loop. This study was designed to analyze the mutation of D835 of FLT3, which corresponds to D816 of c-KIT, in a large series of human hematologic malignancies. Several kinds of missense mutations were found in 30 of the 429 (7.0%) AML cases, 1 of the 29 (3.4%) myelodysplastic syndrome (MDS) cases, and 1 of the 36 (2.8%) acute lymphocytic leukemia patients. The D835Y mutation was most frequently found (22 of the 32 D835 mutations), followed by the D835V (5), and D835H (1), D835E (1), and D835N (1) mutations. Of note is that D835 mutations occurred independently of FLT3/ITD. An analysis in the 201 patients newly diagnosed with AML (excluding M3) revealed that, in contrast to the FLT3/ITD mutation (n = 46), D835 mutations (n = 8) were not significantly related to the leukocytosis, but tended to worsen disease-free survival. All D835-mutant FLT3 were constitutively tyrosine-phosphorylated and transformed 32D cells, suggesting these mutations were constitutively active. These results demonstrate that the FLT3 gene is the target most frequently mutated to become constitutively active in AML.

Effects of sesquiterpenoids from "Oriental incenses" on acetic acid-induced writhing and D2 and 5-HT2A receptors in rat brain.

Six sesquiterpenoids, namely jinkoh-eremol, agarospirol, alpha- and beta-santalols, dehydrocostus lactone and costunolide, isolated from oriental incenses inhibited acetic acid-induced writhing in mice. The incidence of writhing produced by jinkoh-eremol, alpha-santalol and costunolide were revealed by administration of naloxone (mu-, kappa- and delta-antagonists). Inhibitory activities of alpha-santalol on opioid receptors were shown only by the delta antagonist, but not by the mu- and kappa-antagonists. The delta2-antagonist, but not the delta-antagonist, inhibited the activity of alpha santalol. The mechanism of inhibitory activity on the opioid receptor by alpha-santalol was different from that of morphine. Alpha-santalol was shown to be the most potent of the six as an antagonist of dopamine D2 and serotonine 5-HT2A receptor binding. The effect of alpha-santalol, was the same as that of chlorpromazine as an antipsychotic agent, although alpha-santalol was less potent than chlorpromazine.

[Chemotherapy based on EBM in the field of hematological malignancies].

In the field of hematology/oncology, there are reasonable number of chemotherapy-related reports with level 1 evidences based on the analysis of the evidence based medicine (EBM). Following reasons may be pointed out; the first is that the history of chemotherapy has been initiated in the field of in hematology/oncology so it has more than 50 years' experience. The second is that leukemia and lymphoma are very chemosensitive diseases to compare with solid tumor, so the ultimate goal of their therapy is increase of the cure rate. The third is hematologists with high specialty only can manage such serious patients. Thus they have proposed plenty well-designed and well-organized clinical protocols and have performed some of them in this field. We have learned several recommended therapy of some hematological malignancies with level 1 evidences. It is not so easy, however, to treat all patients according to the best recommended therapy for Japanese patients, because of some limitations of using Japanese health insurance. This is very crucial problem for the patients. We should settle the issue from the scientific and social aspects as soon as possible.

New models of health and diseases--holistic and life-span developmental approach.

New models which have been growing in health and medical related disciplines were reviewed. Human life and development are the process by which individuals interact with their environment and innumerable variables. Therefore it is a limitation to depend on traditional disease model only in rapidly changing developed-countries. Several health related models may provide a useful strategy to multidisciplinary investigators for prevention oriented research and practice, though they have to be specialized in each discipline.

Subcellular localization and protein interaction of the human LIMK2 gene expressing alternative transcripts with tissue-specific regulation.

In our efforts to explore possible roles of proteins with a LIM domain, which is a cysteine-rich Zinc-binding motif, in differentiation and oncogenesis in the lung, we have cloned a human LIMK2 gene and identified two alternative transcripts, LIMK2a and LIMK2b, which are probably due to variation in transcriptional initiation. The former encodes a protein containing two LIM domains, a PDZ domain, and a kinase domain, while the latter has only one and half LIM domains. The predominance of the two transcripts appears to be regulated in a tissue-specific manner. Alteration of the regulation is also observed in some cancer cell lines. Transfection studies have shown an association of 63-kDa and 58-kDa proteins with the LIMK2a and LIMK2b protein; the former is distributed in the cytoplasm and nucleus and the latter occurs mainly in the cytoplasm and is scarcely translocated to the nucleus. In contrast, a truncated LIMK2-Kinase has a nuclear location, not showing the protein association.

Effect of jinkoh-eremol and agarospirol from agarwood on the central nervous system in mice.

Agarwood (Jinkoh in Japanese), one of the Oriental medicines, is used as a sedative. The benzene extract of this medicine showed a prolonged effect on the hexobarbital-induced sleeping time, and hypothermic effects in terms of rectal temperature, a suppressive effect on acetic acid-writhing, and a reduction of the spontaneous motility in mice. By repeated fractionation, oral administration in mice, and pharmacological screening, the active principles, jinkoh-eremol and agarospirol, were obtained from the benzene extract. They also gave positive effects on the central nervous system by peritoneal and intracerebroventricular administration. They decreased both methamphetamine- and apomorphine-induced spontaneous motility. The level of homovanillic acid in the brain was increased by them, while the levels of monoamines and other metabolites were unchanged. Similar results were seen in chlorpromazine-administered mice. Therefore, jinkoh-eremol and agarospirol can be considered to be neuroleptic.

Effect of dehydrocostus lactone and costunolide from Saussurea root on the central nervous system in mice.

Saussurea root (Mokko in Japanese; root of Saussurea lappa, Compositae) is an aromatic stomachic and sedative in Oriental medicine. Four extracts of saussurea root were obtained by successively extracting with benzene, chloroform, methanol and water. Each of these extracts was tested for effects on the central nervous system (CNS) of mice by intraperitoneal administration, i. e. potentiation of hexobarbital sleeping time, body temperature alterations, antinociceptive effects, and spontaneous locomotor activity changes. The benzene extract was the most active and was then separated further into five fractions, 1,2,3,4, and 5 by column chromatography. Fraction 2 was shown to be the most active in the aforementioned assays. From this fraction dehydrocostus lactone and costunolide were isolated as the CNS active constituents. They were both active by the intraperitoneal, intragastric and intracerebroventricular routes of administration. They decreased both methamphetamine- and apomorphine-induced spontaneous motility. The level of homovanillic acid in the brain was increased following their administration, while the levels of monoamines and other metabolites were unchanged. Similar results were seen in chlorpromazine-treated mice. These results show that dehydrocostus lactone and costunolide can be considered as neuroleptics by resemblance of their pharmacological activities to chlorpromazine.

Effect of α-santalol and ß-santalol from sandalwood on the central nervous system in mice.

Sandalwood (Byakudan in Japanese; Santalum album L.) is used as a popular sedative in Oriental medicine. Extracts of the wood of Santalum album were obtained by successively extracting with benzene, chloroform, methanol and water. Each of these fractions was tested for activity on the central nervous system of mice following intraperitoneal administration, i.e. potentiation of hexobarbital sleeping time, body temperature alterations, antinociceptive and spontaneous motor activity changes. The benzene extract was active in these assays and was then separated further into fractions 1, 2 and 3. Fraction 2 was shown to be the most active in the aforementioned assays, α- and ß-Santalols were isolated from this active fraction as the major CNS active constituents. They were both active by the intragastric and intracerebroventricular routes of administration. Thus, it can be considered that α- and ß-santalols contribute to the reputed sedative effect of sandalwood preparations in Oriental medicine. Additionally, α- and ß-santalols significantly increased the levels of homovanillic acid, 3,4-dihydroxyphenylacetic acid and/or 5-hydroxyindoleacetic acid in the brain of mice, and chlorpromazine did the ones of homovanillic acid and 3,4-dihydroxyphenylacetic acid. These results showed that α- and ß-santalols could be considered as neuroleptic by resemblance to the pharmacological activities of chlorpromazine.

Effect of hyperthermia on tumor uptake of radiolabeled anti-neural cell adhesion molecule antibody in small-cell lung cancer xenografts.

UNLABELLED: This study was performed to examine the effect of hyperthermia on the intratumor accumulation of a monoclonal antibody (Mab) in an animal model. Mab NE150 (IgG1) recognizes the neural cell adhesion molecule (NCAM) expressed by human small-cell lung cancer (SCLC) cells. METHODS: Athymic mice inoculated with NCI-H69, an SCLC cell line, received an intravenous injection of 125I- and 111In-NE150 and the serial changes of the biodistribution were determined. Furthermore, athymic mice bearing NCI-H69 were either sham-treated or treated by a single hyperthermia at 42 degrees C or 43 degrees C for 1 hr, with the tumor-bearing leg in a water bath using pentobarbital anesthesia. Immediately after heating, the mice were given an intravenous injection of radiolabeled NE150, and the biodistribution was examined at 24 and 48 hr. RESULTS: NE150 localized well in the transplanted tumor when compared with a control Mab. In mice treated at 43 degrees C, there was a 1.34- to 1.67-fold increase in the tumor uptake of 125I- and 111In-NE150 compared to sham-treated mice at both 24 and 48 hr. In addition, a 1.84- to 2.22-fold increase of the tumor-to-blood ratio was demonstrated, since radiolabeled NE150 cleared faster from the circulation in the mice given hyperthermia. A histological study demonstrated the infiltration of neutrophils in the perivascular spaces, indicating an increase of tumor vascular permeability, which might be one of the main reasons for the enhancement of Mab uptake. CONCLUSION: Hyperthermia seems to be a potential method of achieving an increased tumor accumulation of Mab in the radioimmunotargeting of SCLC.

Effects of agarwood extracts on the central nervous system in mice.

Agarwood (Jinkoh in Japanese) is an Oriental medicine for use as a sedative. Neuropharmacological studies have been conducted with the extracts of petroleum ether, benzene, chloroform, and water from agarwood (Aquilaria sp.; probably Aquilaria malaccensis Benth.) in mice. The benzene extract showed a reducing effect in spontaneous motility, a prolonging effect on hexobarbiturate-induced sleeping time, a hypothermic effect in terms of rectal temperature, and a suppressive effect on acetic acid-writhing by oral administration. Fr. 1 of the three fractions which were obtained from the benzene extract by column chromatography was found to produce more positive effects on these neuropharmacological tests than the original benzene extract. These facts suggest that the benzene extractable compounds of agarwood possess potent central nervous system depressant activities.

[Clinical evaluation of TMS-19-Q, a new macrolide antibiotic, in otorhinolaryngological infections].

The clinical study for TMS-19-Q.O tablet was performed with multicenter trial. The results obtained were as follows; Final global improvement rating in 332 cases of otorhinolaryngological infections were excellent in 99, good in 142, fair in 40 and poor in 51 and the effective rate was 72.6%. Those of 266 cases with acute infection were excellent in 93 and good in 121 and the effective rate was 80.5%. Optimum daily doses would be 600 mg based on the analysis of 144 cases of the acute infection with sensitive bacteria (MIC: less than or equal to 3.13 micrograms/ml). In acute infection, major causative bacteria were Gram-positive cocci (GPC) indicating the frequency of 72.0% in total isolates and 87.5% in singly isolated cases. In chronic infection, although GPC were also dominant, Gram-negative bacilli were observed in 31.9%. Clinical and bacteriological effective rates of 160 cases of acute infection with single species were 80.6% and 90.3%, and those of 43 cases in chronic infection were 44.2% and 72.7%, respectively. The resistant rates of isolates in acute infection to TMS-19-Q were 13.3% in S. aureus, 7.7% in S. epidermidis, 6.0% in S. pyogenes and 0% in S. pneumoniae. Those in chronic infection were 20.0% in S. aureus and 25.0% in S. epidermidis. Slight adverse reactions, such as skin eruption or gastrointestinal disorders were observed in 14 cases and no severe one was observed. Slight elevation of GOT, GPT, Al-P, BUN, S-Cr. or eosinophil were observed in 12 cases. These results suggest that TMS-19-Q would be useful antibiotic for otorhinolaryngological infections.