Finite element analysis of masticatory stress on neoformed bone tissue after distraction osteogenesis and low-level laser therapy: a pilot study.

OBJECTIVE: This study aimed to understand the action of masticatory forces on an implant virtually introduced into the sheep mandible after distraction osteogenesis and low-level laser therapy (LLLT) by using finite element analysis. BACKGROUND DATA: Distraction osteogenesis as an alternative for bone reconstruction that may be used in the treatment of deformities. METHODS: Four ewes underwent distraction osteogenis to elongate the left mandibular body by 15 m, and three of them underwent LLLT with the purpose of improving bone properties. After death, animals were scanned by computed tomography and their mandibles were tridimensionally reconstructed by computer programs. The physical properties related to hardness and modulus of elasticity of each animal were obtained from the dissected mandibles, and data were transferred to Femap software for finite element analysis. RESULTS: Animals exposed and not exposed to LLLT irradiation showed remarkably similar values for superficial hardness and modulus of elasticity, without statistically significant difference (p>0.05), between the values observed for the cortical bone and the cancellous bone among the groups. The neoformed mandible, after a brief period for bone healing, was able to promote stability for implant placement and proper distribution of masticatory forces. CONCLUSIONS: An implant introduced virtually into the site of bone neoformation did not suffer any micromotions relevant to osteointegration. Furthermore, finite element analysis showed that the neoformed portion of the mandible was able to absorb and distribute masticatory forces throughout its structure, even after a brief period for bone maturation.

Calcium and vitamin D supplementation is associated with decreased abdominal visceral adipose tissue in overweight and obese adults.

BACKGROUND: Several studies suggest that calcium and vitamin D (CaD) may play a role in the regulation of abdominal fat mass. OBJECTIVE: This study investigated the effect of CaD-supplemented orange juice (OJ) on weight loss and reduction of visceral adipose tissue (VAT) in overweight and obese adults (mean ± SD age: 40.0 ± 12.9 y). DESIGN: Two parallel, double-blind, placebo-controlled trials were conducted with either regular or reduced-energy (lite) orange juice. For each 16-wk trial, 171 participants were randomly assigned to 1 of 2 groups. The treatment groups consumed three 240-mL glasses of OJ (regular or lite) fortified with 350 mg Ca and 100 IU vitamin D per serving, and the control groups consumed either unfortified regular or lite OJ. Computed tomography scans of VAT and subcutaneous adipose tissue were performed by imaging a single cut at the lumbar 4 level. RESULTS: After 16 wk, the average weight loss (∼2.45 kg) did not differ significantly between groups. In the regular OJ trial, the reduction of VAT was significantly greater (P = 0.024) in the CaD group (-12.7 ± 25.0 cm(2)) than in the control group (-1.3 ± 13.6 cm(2)). In the lite OJ trial, the reduction of VAT was significantly greater (P = 0.039) in the CaD group (-13.1 ± 18.4 cm(2)) than in the control group (-6.4 ± 17.5 cm(2)) after control for baseline VAT. The effect of calcium and vitamin D on VAT remained highly significant when the results of the 2 trials were combined (P = 0.007). CONCLUSIONS: The findings suggest that calcium and/or vitamin D supplementation contributes to a beneficial reduction of VAT. This trial is registered at clinicaltrial.gov as NCT00386672, NCT01363115.

Expression and localization of an agmatinase-like protein in the rat brain.

Agmatinase catalyzes the hydrolysis of agmatine into putrescine and urea, and agmatine (decarboxylated L: -arginine) plays several roles in mammalian tissues, including neurotransmitter/neuromodulatory actions in the brain. Injection of agmatine in animals produces anticonvulsant, antineurotoxic and antidepressant-like actions. Information regarding the enzymatic aspects of agmatine metabolism in mammals, especially related to its degradation, is relatively scarce. The explanation for this is the lack of enzymatically active preparations of mammalian agmatinase. Recently, we have cloned a protein from a cDNA rat brain library having agmatinase activity although its amino acid sequence greatly differs from all known agmatinases, we called agmatinase-like protein. In this work, we analyzed the expression of this enzyme in the rat brain by means of RT-PCR and immunohistochemical analysis using a polyclonal antibody generated against the recombinant agmatinase-like protein. The agmatinase-like protein was detected in the hypothalamus in glial cells and arcuate nucleus neurons, and in hippocampus astrocytes and neurons, but not in brain cortex. In general, detected localization of agmatinase-like protein coincides with that described for its substrate agmatine and our results help to explain several reported effects of agmatine in the brain. Concretely, a role in the regulation of intracellular concentrations of the neurotransmitter/neuromodulator agmatine is suggested for the brain agmatinase-like protein.

Cuatro compuestos nuevos del extracto no polar de la planta Amyris brenesii (Rutaceae) de Costa Rica

Four new compounds from the non-polar extract of the plant Amyris brenesii (Rutaceae) from Costa Rica. Fractionation of a non polar extract of the aerial parts of Amyris brenesii collected in Río Cuarto, Grecia, Costa Rica has resulted in the isolation of four new compounds, 6-hidroxy-6-O-(3-hidroxymethyl-3methylalyl)-angelicin 1, 6-(N-acetyl-2-etanamin)-2,2-dimethyl-2H-cromen 2, the lignan 2,5-dehidrohinokinin 3 and N-acetyl-O-(geranyl)-tiramine 4. In addition, we isolated six previously known compounds: the lignans hinokinin 5 and Justicidin E 6, the coumarins scopoletin 7 and marmesin 8, 24-moretenoic acid 9, and the nitrogen compound O-(3,3-dimethylalyl)-halfordinol 10. All the separations were done with chromatographic techniques and the structures were elucidated by using 1D and 2D NMR techniques. Rev. Biol. Trop. 56 (3): 1043-1052. Epub 2008 September 30.

El estudio fitoquímico de las partes aéreas de Amyris brenesii (Rutaceae) recolectadas en Río Cuarto, Grecia, Alajuela (Costa Rica) mostró la presencia de cuatro nuevos compuestos: la 6-hidroxi-6-O-(3-hidroximetil-3-metilalil)angelicina 1, el 6-(N-acetil-2-etanamin)-2,2-dimetil-2Hcromeno 2, el lignano 2,5-deshidrohinokinina 3 y la N-acetil-O-(geranil)-tiramina 4. Adicionalmente se aislaron los lignanos hinokinina 5, y justicidina E 6, las cumarinas escopoletina 7 y marmesina 8, el ácido 24-moretenoico 9 y el O-(3,3-dimetilalil)-halfordinol 10. Las separaciones se llevaron a cabo mediante la aplicación de técnicas cromatográficas y la elucidación de las estructuras se realizó con la ayuda de técnicas espectroscópicas de Resonancia Magnética Nuclear (RMN) de una y dos dimensiones.

[Four new compounds from the non-polar extract of the plant Amyris brenesii (Rutaceae) from Costa Rica]. / Cuatro compuestos nuevos del extracto no polar de la planta Amyris brenesii (Rutaceae) de Costa rica.

Fractionation of a non polar extract of the aerial parts of Amyris brenesii collected in Rio Cuarto, Grecia, Costa Rica has resulted in the isolation of four new compounds, 6-hidroxy-6-O-(3-hidroxymethyl-3-methylalyl)-angelicin 1, 6-(N-acetyl-2-etanamin)-2,2-dimethyl-2H-cromen 2, the lignan 2,5-dehidrohinokinin 3 and N-acetyl-O-(geranyl)-tiramine 4. In addition, we isolated six previously known compounds: the lignans hinokinin 5 and Justicidin E 6, the coumarins scopoletin 7 and marmesin 8, 24-moretenoic acid 9, and the nitrogen compound O-(3,3-dimethylalyl)-halfordinol 10. All the separations were done with chromatographic techniques and the structures were elucidated by using 1D and 2D NMR techniques.

Oxazolones as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 1.

2,5,5-Trisubstituted oxazolones were identified as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). The synthesis, structure-activity relationship and metabolic stability of these compounds are presented.

Inhibitory effects of Piper umbellatum and Piper peltatum extracts towards myotoxic phospholipases A2 from Bothrops snake venoms: isolation of 4-nerolidylcatechol as active principle.

Phospholipases A(2) (PLA(2)) are important constituents of snake venoms, being responsible for several of their toxic actions. Extracts from plants used in folk medicine were screened for inhibition of the enzymatic activity of myotoxin I, a PLA(2) from Bothrops asper. Piper umbellatum and Piper peltatum extracts tested positive, and their fractionation resulted in the isolation of 4-nerolidylcatechol. Its inhibitory effects towards toxic activities of two Bothrops myotoxins, representing catalytically active (Asp49) and catalytically inactive (Lys49) types of group II PLA(2)s, respectively, were characterized. The enzyme activity of B. asper myotoxin I was completely inhibited by 4-nerolidylcatechol at an inhibitor:toxin ratio of 10:1 (wt/wt) with an IC50 of approximately 1mM. In addition, 4-nerolidylcatechol inhibited representatives of groups I and III of PLA(2)s. Its preincubation with Bothrops myotoxins significantly reduced their myotoxic and edema-inducing activities in animal experiments. However, when 4-nerolidylcatechol was administered in situ, immediately after toxin injection, its inhibitory ability was substantially lower or negligible. This might be explained by the rapid action of these toxins in vivo, together with the slow inactivation of PLA(2) activity observed in vitro. Electrophoretic and chromatographic analyses of myotoxins ruled out major changes in protein charge, hydrophobicity, or gross molecular mass being involved in the inhibition mechanism. Mass spectrometry determinations are consistent with the covalent modification of myotoxin by one molecule of 4-nerolidylcatechol. Finally, a novel compound was isolated from both Piper species, sharing the nerolidyl skeleton, but nevertheless not being inhibitory towards the PLA(2)s studied.

Quantitative structure-activity relationship of sesquiterpene lactones as inhibitors of the transcription factor NF-kappaB.

Sesquiterpene lactones (SLs) are the active compounds of a variety of traditionally used medicinal plants from the Asteraceae family. They are known to possess a considerable antiinflammatory activity in different inflammation models. They inhibit the transcription factor NF-kappaB probably by alkylating cysteine38 in the DNA binding domain of the p65 subunit. Here we investigate a set of 103 different sesquiterpene lactones representing 6 structural groups (44 germacranolides, 16 heliangolides, 22 guaianolides, 9 pseudoguaianolides, 2 hypocretenolides, 10 eudesmanolides) for their NF-kappaB inhibiting properties and the resulting IC(100)-values were submitted to a QSAR study. Properties important for the inhibition potency are discussed for the whole data set and for subsets of the different structural classes.

Studies of ent-kaurane diterpenes from Oyedaea verbesinoides for their inhibitory activity on vascular smooth muscle contraction.

From the aerial parts of Oyedaea verbesinoides nine ent-kauranes and a sesquiterpene were isolated. ent-9alpha-Hydroxy-kaur-16-en-19-oic acid, ent-15beta-tigloyloxy-9alpha-hydroxy-kaur-16-en-19-oic acid, ent-15beta-angeloyloxy-9alpha-hydroxy-kaur-16-en-19-oic acid, ent-16alpha-hydroxykaurane and 1alpha-angeloyloxy-carotol are new for the genus or the species and ent-15beta-angeloyloxy-7alpha,9alpha-dihydroxy-kaur-16-en-19-oic acid is reported for the first time. Structure elucidation was based on one and two dimensional NMR as well as ESI and CI-MS analysis. Some diterpenes were proven to exhibit inhibitory effects on smooth muscle contraction on rat aorta.

The effect of sesquiterpene lactones on the release of human neutrophil elastase.

Sesquiterpene lactones (SLs) are natural products responsible for the anti-inflammatory activity of a variety of medicinal plants, mainly from the Asteraceae family. Here, we investigated whether they also influence the process of exocytosis of pro-inflammatory enzymes, such as the human neutrophil elastase (HNE). Altogether, eight structurally different SLs from the eudesmanolide, guaianolide, pseudoguaianolide, and germacranolide type were studied. Neutrophils were isolated from fresh human blood. After pre-incubation with different concentrations of the respective SL and cytochalasin B, the exocytosis of elastase was initiated either by platelet activating factor or N-formyl-methionyl-leucyl-phenylalanine. Inhibition of HNE release was measured by p-nitroaniline formation. The SLs exhibited an inhibitory effect on elastase release from neutrophils challenged either by platelet activating factor or N-formyl-methionyl-leucyl-phenylalanine. Concentration-response curves were recorded and the IC(50) values ranged from 2 to 30 microM. Studies on isolated HNE showed that a selective direct inhibition on HNE can be excluded. Interestingly, the inhibitory activity did not correlate with the number of alpha,beta-unsaturated carbonyl functions. The structure-activity relationship and the molecular mechanism are discussed.