Κυριακή, 2 Οκτωβρίου 2016

Does dexmedetomidine cause less airway collapse than propofol when used for deep sedation?

The risk of airway collapse in patients undergoing deep sedation is a major concern. In this study, we compared the airway patency of deep sedation provided by propofol with the airway patency of deep sedation provided by dexmedetomidine in magnetic resonance imaging (MRI) procedures. This comparison was done using MRI static and dynamic images and comparing these images to baseline after sevoflurane induction.

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Seldinger technique for nasal intubation: a case series.

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Seldinger technique for nasal intubation: a case series.

J Clin Anesth. 2016 Nov;34:609-11

Authors: Abrons RO, Vansickle RA, Ouanes JP

Abstract
Nasotracheal intubation can be both challenging and traumatic, especially in cases of atypical anatomy. We present a series of 3 such cases in which an endotracheal tube introducer (bougie) was used to facilitate successful, atraumatic, nasotracheal intubation via Seldinger technique. The technique described can guide a nasotracheal tube through narrow nasal passages, small pharyngeal spaces, and past acute laryngeal approach angles, all without transoral manipulation of the tube. The technique is easy to perform, uses a routine skill set, and can be advantageous in numerous clinical scenarios.

PMID: 27687457 [PubMed - in process]



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Possible association between successful intubation via the right nostril and anatomical variations of the nasopharynx during nasotracheal intubation: a multiplanar imaging study.

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Possible association between successful intubation via the right nostril and anatomical variations of the nasopharynx during nasotracheal intubation: a multiplanar imaging study.

J Anesth. 2016 Sep 27;

Authors: Takasugi Y, Futagawa K, Konishi T, Morimoto D, Okuda T

Abstract
PURPOSE: Most reported cases of nasopharyngeal laceration following impingement during nasotracheal intubation involved tube insertion via the right nostril. We postulated that recesses on the posterior wall of the nasopharynx might be associated with tube impingement. Using multiplanar imaging and clinical statistics, we evaluated whether anatomical variations in the recesses are related to successful intubation via the right nostril.
METHODS: Using multiplanar computed tomography (CT) images of 97 patients, we investigated the locations of recesses relative to the mid-sagittal plane, nasal floor plane and posterior end of the nasal septum, and their shapes. Incidents of impingement of the tube during nasotracheal intubation and the shapes of the fossa of Rosenmüller on CT images were retrospectively evaluated in 170 patients.
RESULTS: Eustachian tube orifices were located approximately 10 mm laterally from the sagittal plane, and approximately 10 mm above the nasal floor plane. The fossa of Rosenmüller was vertically elongated and located 7 mm laterally from the mid-sagittal plane. Pharyngeal bursae were found in 15 % of the subjects. Patients with failed insertion via the right nostril due to impingement frequently had a wide opening of the fossa of Rosenmüller.
CONCLUSIONS: Successful intubation via the right nostril is related to the anatomy of structures on the posterior nasopharyngeal wall, particularly recesses located close to the path of nasotracheal tube insertion. Nasopharyngeal anatomical variations should be considered when one notices any resistance to advancement of the tube into the nasopharynx during nasotracheal intubation.

PMID: 27678497 [PubMed - as supplied by publisher]



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A comparison between the GlideScope® classic and GlideScope® direct video laryngoscopes and direct laryngoscopy for nasotracheal intubation.

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A comparison between the GlideScope® classic and GlideScope® direct video laryngoscopes and direct laryngoscopy for nasotracheal intubation.

J Clin Anesth. 2016 Sep;33:330-6

Authors: Heuer JF, Heitmann S, Crozier TA, Bleckmann A, Quintel M, Russo SG

Abstract
DESIGN: Prospective, randomized, clinical trial.
SETTING: University hospital operation room.
PATIENTS: 104 patients scheduled for elective dental or maxillofacial surgery were randomized to two groups: GlideScope® classic (GSc) and GlideScope® direct (GSd).
INTERVENTIONS: We compared the video laryngoscopes GSc and GSd with each other and with direct laryngoscopy (DL) for nasotracheal intubation with regard to visualization of the glottis, intubation success rate, and required time for and ease of intubation. The aim of the study was to determine whether the use of the video monitor alone reduced the difficulty of nasotracheal intubation, and also to investigate whether the GSc, with its blade designed for difficult airways, had an additional advantage over the video-assisted Macintosh blade (GSd). In both groups the investigators first performed laryngoscopy using the GSd blade, first with the monitor concealed and then with it visible. In the GSd group the tube was then inserted into the trachea with the video monitor screen visible. In the GSc group, the GSd blade was exchanged for the GSc blade, which was then used when inserting the tube with the screen visible.
RESULTS: The success rates and the times required for the video-assisted nasotracheal intubation did not differ significantly between the groups. A better view was obtained more often in the GSc group. In both groups there was a significant difference between direct laryngoscopy and the video-assisted intubation technique. Overall, using the video monitor improved the C-L scores by one grade in 52% and by two grades in 11% of the patients.
CONCLUSIONS: Video laryngoscopes increase the ease of nasotracheal intubation. The GSc blade might provide a better view of the laryngeal structures in case of a difficult airway than the GSd blade. Video laryngoscopy per se gives a better view of the glottis than direct laryngoscopy.

PMID: 27555188 [PubMed - in process]



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A novel method to control the distal tip of nasotracheal tube.

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A novel method to control the distal tip of nasotracheal tube.

J Clin Anesth. 2016 Sep;33:160-1

Authors: Hung KC, Hsieh SW, Liu PH

PMID: 27555153 [PubMed - in process]



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Use of a 90-degree anticlockwise tube rotation to facilitate nasotracheal tube passage over the fiberscope into the trachea in pediatric patients.

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Use of a 90-degree anticlockwise tube rotation to facilitate nasotracheal tube passage over the fiberscope into the trachea in pediatric patients.

Paediatr Anaesth. 2016 May;26(5):565-6

Authors: Xue FS, Liu GP, Sun C

PMID: 27059418 [PubMed - indexed for MEDLINE]



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Surgical intervention during a Can't intubate Can't Oxygenate (CICO) Event: Emergency Front-of-neck Airway (FONA)?

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Surgical intervention during a Can't intubate Can't Oxygenate (CICO) Event: Emergency Front-of-neck Airway (FONA)?

Br J Anaesth. 2016 Sep 19;

Authors: Pracy JP, Brennan L, Cook TM, Hartle AJ, Marks RJ, McGrath BA, Narula A, Patel A

PMID: 27646054 [PubMed - as supplied by publisher]



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Transtracheal jet ventilation in the 'can't intubate can't oxygenate' emergency: a systematic review.

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Transtracheal jet ventilation in the 'can't intubate can't oxygenate' emergency: a systematic review.

Br J Anaesth. 2016 Sep;117 Suppl 1:i28-i38

Authors: Duggan LV, Ballantyne Scott B, Law JA, Morris IR, Murphy MF, Griesdale DE

Abstract
BACKGROUND: Transtracheal jet ventilation (TTJV) is recommended in several airway guidelines as a potentially life-saving procedure during the 'Can't Intubate Can't Oxygenate' (CICO) emergency. Some studies have questioned its effectiveness.
METHODS: Our goal was to determine the complication rates of TTJV in the CICO emergency compared with the emergency setting where CICO is not described (non-CICO emergency) or elective surgical setting. Several databases of published and unpublished literature were searched systematically for studies describing TTJV in human subjects. Complications were categorized as device failure, barotrauma (including subcutaneous emphysema), and miscellaneous. Device failure was defined by the inability to place and/or use the TTJV device, not patient survival.
RESULTS: Forty-four studies (428 procedures) met the inclusion criteria. Four studies included both emergency and elective procedures. Thirty studies described 132 emergency TTJV procedures; 90 were CICO emergencies. Eighteen studies described 296 elective TTJV procedures. Device failure occurred in 42% of CICO emergency vs 0% of non-CICO emergency (P<0.001) and 0.3% of elective procedures (P<0.001). Barotrauma occurred in 32% of CICO emergency vs 7% of non-CICO emergency (P<0.001) and 8% of elective procedures (P<0.001). The total number of procedures with any complication was 51% of CICO emergency vs 7% of non-CICO emergency (P<0.001) and 8% of elective procedures (P<0.001). Several reports described TTJV-related subcutaneous emphysema hampering subsequent attempts at surgical airway or tracheal intubation.
CONCLUSIONS: TTJV is associated with a high risk of device failure and barotrauma in the CICO emergency. Guidelines and recommendations supporting the use of TTJV in CICO should be reconsidered.

PMID: 27566790 [PubMed - in process]



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Immunostimulatory activity of brown seaweed-derived fucoidans at different molecular weights and purity levels towards white spot syndrome virus (WSSV)in shrimp Litopenaeus vannamei

2016-10-02T06-42-59Z
Source: Journal of Applied Pharmaceutical Science
Ellya Sinurat, Endang Saepudin, Rosmawaty Peranginangin, Sumi Hudiyono.
White spot syndrome virus (WSSV) is one of the virulent pathogens and causes big economic losses to shrimp aquaculture (Flegel, 2011). In general, most crustaceans have no immune system memory and only rely on innate immunity to protect themself against pathogen infection and other external factors that constantly threatens their lives (Sarathi et al., 2007). Research in the immune response of shrimp has flourished because of its importance in aquaculture and the increasing number of pathogens that arise are found, which may affect an organism's defense system (Bachere et al., 2000). To fight these pathogens, the shrimp using a variety of specific immune mechanisms, including haemocytes mobilization (Johansson and Soderhall, 1989); prophenoloxidase cascade formation (Sritunyalucksana and Soderhall, 2000). The immune system of shrimp is intimately related to its blood (hemolymph), because it contains haemocytes involved in cell's defense mechanisms such as phagocytosis, lysis of foreign units and encapsulation (Soderhall and Smith, 1983; Fuhua and Jianhai, 2013; Dechamag et al., 2006). Prophenoloxidase (proPO) system is an important defense mechanism in crustaceans. This system involves a complex molecular cascade triggered by components of the surface of immunostimulants. A number of immunostimulants that have been used in aquaculture are from the class of polysaccharides derived from bacteria and fungi such as -glucan, lipopolysaccharide (LPS), peptidoglycan, Cynodon dactylon and herbal immunostimulant. In addition to that, there are also immunostimulants derived from seaweeds such as alginate, carrageenan, laminarin and fucoidan. Generally immunostimulatory substances that have been reported so far were less pure or in the form of crude extracts (Chin et al., 2013). Fucoidan has no direct effect on virion, but it plays a role in the defense system through cellular and the humolar mechanisms to fight the virus. Mechanism of antiviral activity of fucoidan is to inhibit the absorption of viruses and the formation of virus-induced syncytium (Mandal et al., 2007). The biologic activities of fucoidans are closely related to their molecular structures, which include fucose linkage, the sugar type, sulfate content, and molecular weight. Among these, molecular weight is one of the most important factors determining the biological activities of polysaccharides.


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Electrophysiology, immunophenotype, and gene expression characterization of senescent and cryopreserved human amniotic fluid stem cells

Abstract

We characterized human amniotic fluid stem cells (AFSC) in senescent cultures (6 weeks) versus cryopreserved cells using whole-cell patch-clamp, immunophenotyping, and differential gene expression profiling for senescence genes. We evidenced five ion current components (outward rectifier, A-type, inward rectifier, and big conductance Ca2+-dependent K+ currents, fast voltage-dependent Na+ currents). Senescent AFSC showed reduced expression of CD90, CD44, CD133, over 500-fold increase of interferon gamma and telomerase reverse transcriptase genes, increased cycle-dependent kinase 4 inhibitors, p53-binding protein 1, and decreased calreticulin and CD44. HLA-ABC immune expression was similar, and HLA-DR expression very low in both cell types. A subset of cryopreserved AFSC featured large inward rectifier K+ currents, voltage-dependent Na+ currents, and neural progenitor markers evidenced by immunophenotyping and RT-PCR. In all AFSC, in both culture conditions, at patch rupture the outward currents were very low, and they increased progressively over several minutes upon cytoplasm dialysis with pipette solution.



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Neuronal circuits and physiological roles of the basal ganglia in terms of transmitters, receptors and related disorders

Abstract

The authors have reviewed recent research advances in basal ganglia circuitry and function, as well as in related disorders from multidisciplinary perspectives derived from the results of morphological, electrophysiological, behavioral, biochemical and molecular biological studies. Based on their expertise in their respective fields, as denoted in the text, the authors discuss five distinct research topics, as follows: (1) area-specific dopamine receptor expression of astrocytes in basal ganglia, (2) the role of physiologically released dopamine in the striatum, (3) control of behavioral flexibility by striatal cholinergic interneurons, (4) regulation of phosphorylation states of DARPP-32 by protein phosphatases and (5) physiological perspective on deep brain stimulation with optogenetics and closed-loop control for ameliorating parkinsonism.



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Different rate-limiting activities of intracellular pH regulators for HCO 3 − secretion stimulated by forskolin and carbachol in rat parotid intralobular ducts

Abstract

Intracellular pH (pHi) regulation fundamentally participates in maintaining HCO3 release from HCO3-secreting epithelia. We used parotid intralobular ducts loaded with BCECF to investigate the contributions of a carbonic anhydrase (CA), anion channels and a Na+–H+ exchanger (NHE) to pHi regulation for HCO3 secretion by cAMP and Ca2+ signals. Resting pHi was dispersed between 7.4 and 7.9. Forskolin consistently decreased pHi showing the dominance of pHi-lowering activities, but carbachol gathered pHi around 7.6. CA inhibition suppressed the forskolin-induced decrease in pHi, while it allowed carbachol to consistently increase pHi by revealing that carbachol prominently activated NHE via Ca2+-calmodulin. Under NHE inhibition, forskolin and carbachol induced the remarkable decreases in pHi, which were slowed predominantly by CA inhibition and by CA or anion channel inhibition, respectively. Our results suggest that forskolin and carbachol primarily activate the pHi-lowering CA and pHi-raising NHE, respectively, to regulate pHi for HCO3 secretion.



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Acknowledgment to reviewers



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Sirtinol abrogates late phase of cardiac ischemia preconditioning in rats

Abstract

The aim of this study was to investigate the effect of sirtinol, as an inhibitor of sirtuin NAD-dependent histone deacetylases, on myocardial ischemia reperfusion injury following early and late ischemia preconditioning (IPC). Rats underwent sustained ischemia and reperfusion (IR) alone or proceeded by early or late IPC. Sirtinol (S) was administered before IPC. Arrhythmias were evaluated based on the Lambeth model. Infarct size (IS) was measured using triphenyltetrazolium chloride staining. The transcription level of antioxidant-coding genes was assessed by real-time PCR. In early and late IPC groups, IS and the number of arrhythmia were significantly decreased (P < 0.05 and P < 0.01 vs IR, respectively). In S + early IPC, incidences of arrhythmia and IS were not different compared with the early IPC group. However, in S + late IPC the IS was different from the late IPC group (P < 0.05). In late IPC but not early IPC, transcription levels of catalase (P < 0.01) and Mn-SOD (P < 0.05) increased, although this upregulation was not significant in the S + late IPC group. Our results are consistent with the notion that different mechanisms are responsible for early and late IPC. In addition, sirtuin NAD-dependent histone deacetylases may be implicated in late IPC-induced cardioprotection.



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Derangement of calcium metabolism in diabetes mellitus: negative outcome from the synergy between impaired bone turnover and intestinal calcium absorption

Abstract

Both types 1 and 2 diabetes mellitus (T1DM and T2DM) are associated with profound deterioration of calcium and bone metabolism, partly from impaired intestinal calcium absorption, leading to a reduction in calcium uptake into the body. T1DM is associated with low bone mineral density (BMD) and osteoporosis, whereas the skeletal changes in T2DM are variable, ranging from normal to increased and to decreased BMD. However, both types of DM eventually compromise bone quality through production of advanced glycation end products and misalignment of collagen fibrils (so-called matrix failure), thereby culminating in a reduction of bone strength. The underlying cellular mechanisms (cellular failure) are related to suppression of osteoblast-induced bone formation and bone calcium accretion, as well as to enhancement of osteoclast-induced bone resorption. Several other T2DM-related pathophysiological changes, e.g., osteoblast insulin resistance, impaired productions of osteogenic growth factors (particularly insulin-like growth factor 1 and bone morphogenetic proteins), overproduction of pro-inflammatory cytokines, hyperglycemia, and dyslipidemia, also aggravate diabetic osteopathy. In the kidney, DM and the resultant hyperglycemia lead to calciuresis and hypercalciuria in both humans and rodents. Furthermore, DM causes deranged functions of endocrine factors related to mineral metabolism, e.g., parathyroid hormone, 1,25-dihydroxyvitamin D3, and fibroblast growth factor-23. Despite the wealth of information regarding impaired bone remodeling in DM, the long-lasting effects of DM on calcium metabolism in young growing individuals, pregnant women, and neonates born to women with gestational DM have received scant attention, and their underlying mechanisms are almost unknown and worth exploring.



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Desensitization of menthol-activated cold receptors in lower extremities during local cooling in young women with a cold constitution

Abstract

To test the hypothesis that topical menthol-induced reactivity of cold sensation and cutaneous vasoconstriction to local cooling is augmented in individuals with a cold constitution, we examined thermal sensation and cutaneous vasoconstrictor responses at menthol-treated and untreated sites in the legs during local skin cooling in young women complaining of chilliness (C group) and young women with no complaint as a normal control group (N group). During local skin cooling, the sensitivity to cold sensation was greater in the C group than in the N group. The application of menthol enhanced the cold sensation at a low temperature in the N group, but not in the C group. Cutaneous vasoconstrictor responses to local skin cooling were not altered by menthol treatment in either of the two groups. These findings suggest the desensitization of menthol-activated cold receptors in the legs of C group subjects, and a minor role of cold receptor activity in cutaneous vasoconstrictor response to local cooling.



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Sodium ion transport participates in non-neuronal acetylcholine release in the renal cortex of anesthetized rabbits

Abstract

This study examined the mechanism of release of endogenous acetylcholine (ACh) in rabbit renal cortex by applying a microdialysis technique. In anesthetized rabbits, a microdialysis probe was implanted into the renal cortex and perfused with Ringer's solution containing high potassium concentration, high sodium concentration, a Na+/K+-ATPase inhibitor (ouabain), or an epithelial Na+ channel blocker (benzamil). Dialysate samples were collected at baseline and during exposure to each agent, and ACh concentrations in the samples were measured by high-performance liquid chromatography. High potassium had no effect on renal ACh release. High sodium increased dialysate ACh concentrations significantly. Ouabain increased dialysate ACh concentration significantly. Benzamil decreased dialysate ACh concentrations significantly both at baseline and under high sodium. The finding that high potassium-induced depolarization does not increase ACh release suggests that endogenous ACh is released in renal cortex mainly by non-neuronal mechanism. Sodium ion transport may be involved in the non-neuronal ACh release.



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The vital prognosis of elderly adults living in a group home in their mid-eighties

Abstract

The purpose of the present study is to evaluate the vital prognoses of elderly people in their mid-eighties living in a group home (GH) compared to age- and sex-matched outpatient clinic (OPC) in an observational study conducted over 6 years. We investigated the association between mortality and general, cardiac, and nutritional parameters, including eicosapentaenoic acid (EPA) in 54 GH residents (83 ± 8 years old) and 57 OPC attendees (83 ± 5 years old). Kaplan–Meier curves and Cox proportional hazard ratio analyses were used to assess the association between EPA drug administration and mortality in the GH residents and OPC attendees, respectively. The 54 GH residents had higher mortality and poorer nutritional states, as indicated by lower EPA/arachidonic acid values (median 0.20 vs 0.55, p < 0.001), and BMI under the condition without EPA drug administration (1800 mg daily) than did the OPC group. The significant factors that differed between survivors and deceased in the GH residents and OPC attendees were nutritional and cardiac factors. Cox proportional hazard ratio analysis confirmed that a possible determinant of the prognosis was a lower incidence of EPA drug administration and lower hemoglobin in GH. Kaplan–Meier curves and Cox proportional hazard ratio analyses revealed that EPA drug administration significantly reduced the relative mortality by 82 % in the GH residents (p < 0.001) but not in the OPC attendees. The vital prognosis in individuals from GHs was potentially improved by EPA drug administration, which was not the case in the OPC group; however, further prospective studies are needed.



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Biological function and mechanism of MALAT-1 in renal cell carcinoma proliferation and apoptosis: role of the MALAT-1–Livin protein interaction

Abstract

Long noncoding RNAs (lncRNAs) have been shown to play a critical role in cancer development and progression. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) is a kidney cancer-associated onco-lncRNA involved in the progression of renal cell carcinoma (RCC). However, the pathological role of lncRNA MALAT-1 in RCC proliferation and metastasis remains poorly understood. This study was designed to investigate the biological role and mechanism of MALAT-1 in RCC proliferation and metastasis. The experiments were performed in human tissues, renal carcinoma cell lines, and nude mice. The expression of lncRNA MALAT-1, Livin mRNA, and the Livin protein was determined by quantitative real-time PCR (qRT-PCR) or a Western blot. The interaction between MALAT-1 and Livin was evaluated by RNA pull-down and RNA binding protein immunoprecipitation (RIP). Cell viability and apoptosis in RCC cell lines were detected using CCK-8 and TUNEL assays. LncRNA MALAT-1 and the Livin protein were highly expressed in RCC tissues, as well as in RCC 786-O and Caki-1 cell lines. MALAT-1 interference contributed to an increase in cell apoptosis and a reduction in the cell viability of 786-O and Caki-1 cells. The increase in apoptosis by si-MALAT-1 was reversed by overexpression of Livin. The RIP results showed that MALAT-1 promoted the expression of the Livin protein in 786-O and Caki-1 cells by enhancing the stability of the protein. Furthermore, the volume of si-MALAT-1-786-O cell xenograft was significantly suppressed. These data indicate that lncRNA MALAT-1-mediated promotion of RCC proliferation and metastasis may be due to the upregulation of the expression of Livin.



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Physiology of the fasciculation potentials in amyotrophic lateral sclerosis: which motor units fasciculate?

Abstract

We set out to study whether in amyotrophic lateral sclerosis (ALS) fasciculation potentials (FPs) arise from the most excitable motor units (MUs). We studied 70 patients with ALS and 18 subjects with benign fasciculation syndrome (BFS). Of the 56 eligible ALS patients, 31 had signs of reinnervation in the right first dorsal interosseous muscle selected for study, and 25 did not. Two needle electrodes were placed in different MUs in each studied muscle. We defined the most excitable MU as that first activated by minimal voluntary contraction. In muscles without reinnervation, the recording site with most frequent FPs had a higher probability of showing the first recruited MU (p < 0.001). No significant difference was found in other patients or in BFS subjects. In very early affected muscles, fasciculating MUs are the most likely to be recruited volitionally. This probably represents hyperexcitability at lower motor neuronal level.



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Functiogenesis of the embryonic central nervous system revealed by optical recording with a voltage-sensitive dye

Abstract

Clarification of the functiogenesis of the embryonic central nervous system (CNS) has long been problematic, because conventional electrophysiological techniques have several limitations. First, early embryonic neurons are small and fragile, and the application of microelectrodes is challenging. Second, the simultaneous monitoring of electrical activity from multiple sites is limited, and as a consequence, spatiotemporal response patterns of neural networks cannot be assessed. We have applied multiple-site optical recording with a voltage-sensitive dye to the embryonic CNS and paved a new way to analyze the functiogenesis of the CNS. In this review, we discuss key points of optical recording in the embryonic CNS and introduce recent progress in optical investigations on the embryonic CNS with special emphasis on the development of the chick olfactory system. The studies clearly demonstrate the usefulness of voltage-sensitive dye recording as a powerful tool for elucidating the functional organization of the vertebrate embryonic CNS.



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Transient receptor potential cation 3 channel regulates melanoma proliferation and migration

Abstract

Melanoma has an extremely poor prognosis due to its rapidly progressive and highly metastatic nature. Several therapeutic drugs have recently become available, but are effective only against melanoma with specific BRAF gene mutation. Thus, there is a need to identify other target molecules. We show here that Transient receptor potential, canonical 3 (TRPC3) is widely expressed in human melanoma. We found that pharmacological inhibition of TRPC3 with a pyrazole compound, Pyr3, decreased melanoma cell proliferation and migration. Similar inhibition was observed when the TRPC3 gene was silenced with short-hairpin RNA (shRNA). Pyr3 induced dephosphorylation of signal transducer and activator of transcription (STAT) 5 and Akt. Administration of Pyr3 (0.05 mg/kg) to mice implanted with human melanoma cells (C8161) significantly inhibited tumor growth. Our findings indicate that TRPC3 plays an important role in melanoma growth, and may be a novel target for treating melanoma in patients.



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Increased urinary lysophosphatidic acid in mouse with subtotal nephrectomy: potential involvement in chronic kidney disease

Abstract

Increased incidence of chronic kidney disease (CKD) with consecutive progression to end-stage renal disease represents a significant burden to healthcare systems. Renal tubulointerstitial fibrosis (TIF) is a classical hallmark of CKD and is well correlated with the loss of renal function. The bioactive lysophospholipid lysophosphatidic acid (LPA), acting through specific G-protein-coupled receptors, was previously shown to be involved in TIF development in a mouse model of unilateral ureteral obstruction. Here, we study the role of LPA in a mouse subjected to subtotal nephrectomy (SNx), a more chronic and progressive model of CKD. Five months after surgical nephron reduction, SNx mice showed massive albuminuria, extensive TIF, and glomerular hypertrophy when compared to sham-operated animals. Urinary and plasma levels of LPA were analyzed using liquid chromatography tandem mass spectrometry. LPA was significantly increased in SNx urine, not in plasma, and was significantly correlated with albuminuria and TIF. Moreover, SNx mice showed significant downregulation in the renal expression of lipid phosphate phosphohydrolases (LPP1, 2, and 3) that might be involved in reduced LPA bioavailability through dephosphorylation. We concluded that SNx increases urinary LPA through a mechanism that could involve co-excretion of plasma LPA with albumin associated with a reduction of its catabolism in the kidney. Because of the previously demonstrated profibrotic activity of LPA, the association of urinary LPA with TIF suggests the potential involvement of LPA in the development of advanced CKD in the SNx mouse model. Targeting LPA metabolism might represent an interesting approach in CKD treatment.



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Lifestyle predictors of oxidant and antioxidant enzyme activities and total antioxidant capacity in healthy women: a cross-sectional study

Abstract

The aim of this study was to identify demographic and modifiable lifestyle factors that may be related to endogenous oxidant and antioxidant activity measured in blood specimens from putatively healthy women recruited at the Roswell Park Cancer Institute (Buffalo, NY, USA). Total glutathione (TGSH), catalase (CAT), CuZn–superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and myeloperoxidase (MPO) activity, and total antioxidant capacity (TAC) were measured in 124 healthy women, and associations with epidemiological factors were tested using general linear models. There were significant differences in oxidant and antioxidant enzyme activities according to lifestyle factors, after adjusting for duration of blood storage and season of blood draw. Compared to women who consumed ≤2.8 servings of fruits and vegetables daily, those consuming >5.3 servings had on average 31 % lower MPO activity (p-trend = 0.02), as a marker of oxidative stress, 16 % higher antioxidant GPx activity (p-trend = 0.08), and 9 % higher TAC (p-trend = 0.05). Obese women (body mass index, BMI ≥ 30) in contrast showed 17 % lower antioxidant GPx activity, 44 % higher MPO activity (p-trend = 0.03), and 10 % higher TAC (p-trend = 0.03) compared to women with normal BMI < 25. Smoking was associated with higher TGSH activity (p-trend = 0.01) and lower TAC (p-trend = 0.05). Higher TAC levels were most strongly associated with increasing age (standardized β = 0.40, p < 0.0001), BMI (standardized β = 0.17, p = 0.03), and GPx activity (standardized β = 0.23, p = 0.005), and inversely associated with CuZn-SOD activity (standardized β = −0.14, p = 0.07). Physical activity levels, multivitamin use, and alcohol intake were not associated with TAC. Our data indicate that endogenous oxidant and antioxidant enzyme activities are associated with lifestyle factors and, therefore, may be potentially modifiable, with implications for risk reduction of chronic conditions related to oxidative stress.



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Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study

Abstract

The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC50 = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU50 = 2.68 ± 0.75 %) or without (GU50 = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.



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