Mandibular Torus with Tongue Movement Disorder: A Case Report

We report a case of movement disorder of the tongue caused by mandibular torus.The patient was a 73-year-old woman. In regards to intraoral findings, painless masses 20 x 15 mm in size that were well-defined, nodular, and of bonelike hardness were found bilaterally in the gingiva on the lingual side of the lower premolars. Tongue movement was limited, as the lingual frenulum was trapped in the area that had been narrowed by the bilateral masses, making it difficult to extend the tongue to its original position and therefore the masses were removed under general anesthesia. After surgery, the course of the patient was favorable, with no tongue movement disorder or other symptoms observed

The Key Factors to Maintain IADL among Japanese Elderly — From the View-point of Bone Quality—

Objective: Bone quality (Stiffness Index: SI) approach to elderly osteoporosis has been accelerating interest in recent years. However, there are few data on the relation between SI and instrumental activities of daily living (IADL). The objective of this study is to present the effective target to maintain IADL among Japanese elderly from the view-point of SI. Methods: SI and IADL-related physical measurement items, such as age, body mass index (BMI), fat mass, muscle mass, hand-grip strength, daily energy expenditure, daily movements, daily steps, maximum walking speed (MWS), usual walking speed (UWS) and maximum bite force (MBF) were examined on Japanese elderly aged≧60-year-old. The data of 374 subjects (134 male, 240 female) were analyzed. Results: Stepwise multiple regression showed that male UWS (standardized regression coefficient β=0.27) and female BMI (β=0.27) were the best predictors of SI. Simple regression analysis showed significant positive linear relation of male UWS and female BMI to SI. Conclusion: SI can be a persuasive tool for indirect IADL evaluation via male UWS and female BMI. From the view-point of SI, we propose that male SI>82.5 and female SI>55.6 are the key factors to maintain IADL keeping male UWS>1.39 m/sec and female BMI>22

Cell lines as in vitro models for drug screening and toxicity studies

Cell culture is highly desirable, as it provides systems for ready, direct access and evaluation of tissues. The use of tissue culture is a valuable tool to study problems of clinical relevance, especially those related to diseases, screening, and studies of cell toxicity mechanisms. Ready access to the cells provides the possibility for easy studies of cellular mechanisms that may suggest new potential drug targets and, in the case of pathological-derived tissue, it has an 'Interesting application in the evaluation of therapeutic agents that potentially may treat the dysfunction. However, special considerations must be addressed to establish stable in vitro function. In primary culture, these factors are primarily linked to greater demands of tissue to adequately survive and develop differentiated conditions in vitro. Additional requirements include the use of special substrates (collagen, laminin, extracellular matrix preparations, etc.), growth factors and soluble media supplements, some of which can be quite complex in their composition. These demands, along with difficulties in obtaining adequate tissue amounts, have prompted interest in developing immortalized cell lines which can provide unlimited tissue amounts. However, cell lines tend to exhibit problems in stability and/ or viability, though they serve as a feasible alternative, especially regarding new potential applications in cell transplant therapy. In this regard, stem cells may also be a source for the generation of various cell types in vitro. This review will address aspects of cell culture system application, with focus on immortalized cell lines, in studying cell function and dysfunction with the primary aim being to identify cell targets for drug screening

Tautomerism of Histidine 64 Associated with Proton Transfer in Catalysis of Carbonic Anhydrase

The imidazole ^N signals of histidine 64 (His^), involved in the catalytic function of human carbonic anhydrase II (hCAII), were assigned unambiguously. This was accomplished by incorporating the labeled histidine as probes for solution NMR analysis, with ^N at ring-N and N^, ^C at ring-C∈1, ^C and ^N at all carbon and nitrogen, or ^N at the amide nitrogen and the labeled glycine with ^C at the carbonyl carbon. Using the pH dependence of ring-^N signals and a comparison between experimental and simulated curves, we determined that the tautomeric equilibrium constant (K_T) of His^ is 1.0, which differs from that of other histidine residues. This unique value characterizes the imidazole nitrogen atoms of His^ as both a general acid (a) and base (b): its ∈2-nitrogen as (a) releases one proton into the bulk, whereas itsδ1-nitrogen as (b) extracts another proton from a water molecule within the water bridge coupling to the zinc-bound water inside the cave. This accelerates the generation of zinc-bound hydroxide to react with the carbon dioxide. Releasing the productive bicarbonate ion from the inside separates the water bridge pathway, in which the next water molecules move into beside zinc ion. A new water molecule is supplied from the bulk to near the δ1-nitrogen of His^. These reconstitute the water bridge. Based on these features, we suggest here a catalytic mechanism for hCAII: the tautomerization of His^ can mediate the transfers of both protons and water molecules at a neutral pH with high efficiency, requiring no time- or energy-consuming processes

A new omega-conotoxin that targets N-type voltage-sensitive calcium channels with unusual specificity.

A new specific voltage-sensitive calcium channel (VSCC) blocker has been isolated from the venom of the fish-hunting cone snail Conus consors. This peptide, named omega-Ctx CNVIIA, consists of 27 amino acid residues folded by 3 disulfide bridges. Interestingly, loop 4, which is supposed to be crucial for selectivity, shows an unusual sequence (SSSKGR). The synthesis of the linear peptide was performed using the Fmoc strategy, and the correct folding was achieved in the presence of guanidinium chloride, potassium buffer, and reduced/oxidized glutathione at 4 degrees C for 3 days. Both synthetic and native toxin caused an intense shaking activity, characteristic of omega-conotoxins targeting N-type VSCC when injected intracerebroventricularly to mice. Binding studies on rat brain synaptosomes revealed that the radioiodinated omega-Ctx CNVIIA specifically and reversibly binds to high-affinity sites with a K(d) of 36.3 pM. Its binding is competitive with omega-Ctx MVIIA at low concentration (K(i) = 2 pM). Moreover, omega-Ctx CNVIIA exhibits a clear selectivity for N-type VSCCs versus P/Q-type VSCCs targeted respectively by radioiodinated omega-Ctx GVIA and omega-Ctx MVIIC. Although omega-Ctx CNVIIA clearly blocked N-type Ca(2+) current in chromaffin cells, this toxin did not inhibit acetylcholine release evoked by nerve stimuli at the frog neuromuscular junction, in marked contrast to omega-Ctx GVIA. omega-Ctx CNVIIA thus represents a new selective tool for blocking N-type VSCC that displays a unique pharmacological profile and highlights the diversity of voltage-sensitive Ca(2+) channels in the animal kingdom

Knockdown of Myo-Inositol transporter SMIT1 normalizes cholinergic and glutamatergic function in an immortalized cell line established from the cerebral cortex of a trisomy 16 fetal mouse, an animal model of human trisomy 21 (Down Syndrome)

The Na+/myo-inositol cotransporter (SMIT1) is overexpressed in human Down syndrome (DS) and in trisomy 16 fetal mice (Ts16), an animal model of the human condition. SMIT1 overexpression determines increased levels of intracellular myo-inositol, a precursor of phophoinositide synthesis. SMIT1 is overexpressed in CTb cells, an immortalized cell line established from the cerebral cortex of a Ts16 mouse fetus. CTb cells exhibit impaired cytosolic Ca2+ signals in response to glutamatergic and cholinergic stimuli (increased amplitude and delayed time-dependent kinetics in the decay post-stimulation), compared to our CNh cell line, derived from the cerebral cortex of a euploid animal. Considering the role of myo-inositol in intracellular signaling, we normalized SMIT1 expression in CTb cells using specific mRNA antisenses. Forty-eight hours post-transfection, SMIT1 levels in CTb cells reached values comparable to those of CNh cells. At this time, decay kinetics of Ca2+ signals induced by either glutamate, nicotine, or muscarine were accelerated in transfected CTb cells, to values similar to those of CNh cells. The amplitude of glutamate-induced cytosolic Ca2+ signals in CTb cells was also normalized. The results suggest that SMIT1 overexpression contributes to abnormal cholinergic and glutamatergic Ca2+ signals in the trisomic condition, and knockdown of DS-related genes in our Ts16-derived cell line could constitute a relevant tool to study DS-related neuronal dysfunction.Fondecyt (Chile) 1040862 1130241 Univ. of Chile Enlaces ENL 07/05 CNRS/Conicyt Exchange Program Fondation J. Lejeune (France) ICM-ECONOMIA, Chile P09-022-F Millennium Scientific Initiative of the Ministerio de Economia, Fomento y Turism