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Biomedical subjects

B E Jones

Publications and source records attributed to B E Jones.

At least 19 recordsLinked to original sources

A scintigraphic investigation of the disintegration behaviour of capsules in fasting subjects: a comparison of hypromellose capsules containing carrageenan as a gelling agent and standard gelatin capsules.

Two-piece hard shell capsules made from hypromellose (or hydroxypropyl methylcellulose, HPMC) have been proposed as an alternative to conventional gelatin capsules for oral drug delivery; however, little is known about their in vivo behaviour. The aim of this study was to compare the disintegration of HPMC and gelatin capsules in fasted human subjects using the technique of gamma scintigraphy. HPMC capsules containing carrageenan as a gelling agent (QUALI-V(R), Qualicaps) and gelatin capsules (Qualicaps) of size 0 were filled with a lactose-based mixture. The capsules were separately radiolabelled with indium-111 and technetium-99m. Both capsules were administered simultaneously with 180ml water to eight healthy male subjects following an overnight fast. Each volunteer was positioned in front of the gamma camera and sequential 60s images were acquired in a continuous manner for 30min. No differences in the oesophageal transit of the two types of capsules were noted, with the capsules arriving in the stomach in a matter of seconds. All the capsules disintegrated in the stomach. The mean (+/-S.D.) disintegration time for the HPMC capsules was 9+/-2min (range 6-11min). The corresponding mean time for the gelatin capsules was 7+/-4min (range 3-13min). These disintegration times were not significantly different (P=0.108, paired t-test). In conclusion, HPMC and gelatin capsules show rapid and comparable in vivo disintegration times in the fasted state. HPMC capsules containing carrageenan as a gelling agent therefore offer a practical alternative to gelatin capsules as an oral drug delivery carrier.

Adult↗

Stereological estimates of the basal forebrain cell population in the rat, including neurons containing choline acetyltransferase, glutamic acid decarboxylase or phosphate-activated glutaminase and colocalizing vesicular glutamate transporters.

The basal forebrain (BF) plays an important role in modulating cortical activity and influencing attention, learning and memory. These activities are fulfilled importantly yet not entirely by cholinergic neurons. Noncholinergic neurons also contribute and comprise GABAergic neurons and other possibly glutamatergic neurons. The aim of the present study was to estimate the total number of cells in the BF of the rat and the proportions of that total represented by cholinergic, GABAergic and glutamatergic neurons. For this purpose, cells were counted using unbiased stereological methods within the medial septum, diagonal band, magnocellular preoptic nucleus, substantia innominata and globus pallidus in sections stained for Nissl substance and/or the neurotransmitter enzymes, choline acetyltransferase (ChAT), glutamic acid decarboxylase (GAD) or phosphate-activated glutaminase (PAG). In Nissl-stained sections, the total number of neurons in the BF was estimated as approximately 355,000 and the numbers of ChAT-immuno-positive (+) as approximately 22,000, GAD+ approximately 119,000 and PAG+ approximately 316,000, corresponding to approximately 5%, approximately 35% and approximately 90% of the total. Thus, of the large population of BF neurons, only a small proportion has the capacity to synthesize acetylcholine (ACh), one third to synthesize GABA and the vast majority to synthesize glutamate (Glu). Moreover, through the presence of PAG, a proportion of ACh- and GABA-synthesizing neurons also has the capacity to synthesize Glu. In sections dual fluorescent immunostained for vesicular transporters, vesicular glutamate transporter (VGluT) 3 and not VGluT2 was present in the cell bodies of most PAG+ and ChAT+ and half the GAD+ cells. Given previous results showing that VGluT2 and not VGluT3 was present in BF axon terminals and not colocalized with VAChT or VGAT, we conclude that the BF cell population influences cortical and subcortical regions through neurons which release ACh, GABA or Glu from their terminals but which in part can also synthesize and release Glu from their soma or dendrites.

Acetylcholine↗

Excitatory action of hypocretin/orexin on neurons of the central medial amygdala.

The neurons of the lateral hypothalamus that contain hypocretin/orexin (hcrt/orx) are thought to promote arousal through the excitatory action they exert on the multiple areas to which they project within the CNS. We show here that the hcrt/orx peptides can also exert a strong action on the amygdala, a structure known for its implication in emotional aspects of behavior. Indeed, the hcrt/orx peptides, applied in acute rat brain slices, excite a specific class of "low threshold burst" neurons in the central medial (CeM) nucleus which is considered as a major output of the amygdala. These excitatory effects are postsynaptic, mediated by Hcrt2/OX2 receptors and result from the closure of a potassium conductance. They occur on a class of neurons that are also excited by vasopressin acting through V1a receptors. These results suggest that the hcrt/orx system can act through the amygdala to augment arousal and evoke the autonomic and behavioral responses associated with fear, stress or emotion.

Action Potentials↗

Halovivax asiaticus gen. nov., sp. nov., a novel extremely halophilic archaeon isolated from Inner Mongolia, China.

Strain EJ-46T, a novel pleomorphic, aerobic, extremely halophilic member of the Archaea was isolated from sediment of the saline Lake Ejinor, in Inner Mongolia, China. This organism was neutrophilic and required at least 15 % (2.5 M) NaCl for growth. MgCl2 was not required. The isolate was able to grow at pH 6.0-9.0. Optimum growth occurred in media containing 20 % (3.4 M) NaCl at pH 7.0-7.5. Polar lipid analysis revealed the presence of phosphatidylglycerol and phosphatidylglycerol phosphate methyl ester, derived from both C20C20 and C20C25 glycerol diethers. Four glycolipids were detected, one of which may be novel. The DNA G+C content was 60.3 mol%. 16S rRNA gene analysis revealed that strain EJ-46T was a member of the phylogenetic group defined by the family Halobacteriaceae, and the highest 16S rRNA gene similarity values of 94.9 and 94.8 % were obtained with the haloalkaliphilic species of the genus Natronococcus, Natronococcus occultus and Natronococcus amylolyticus, respectively. Based on the phenotypic, genotypic and phylogenetic analyses, it is proposed that the novel isolate should be classified as representing a new genus and species, for which the name Halovivax asiaticus gen. nov., sp. nov. is proposed. The type strain is EJ-46T (=CGMCC 1.4248T = CECT 7098T).

China↗

Gracilibacillus orientalis sp. nov., a novel moderately halophilic bacterium isolated from a salt lake in Inner Mongolia, China.

Three Gram-positive, moderately halophilic, spore-forming rods, designated XH-63T, XH-62 and EJ-15, were isolated from two salt lakes located near Xilin Hot and Ejinor, in Inner Mongolia, China. The strains were strictly aerobic and motile, with spherical, terminal and deforming endospores. They grew at pH 5.0-9.0 (optimal growth at pH 7.5), between 4 and 45 degrees C (optimal growth at 37 degrees C) and at salinities of 1-20% (w/v) total salts, growing optimally at 10% (w/v) salts. They had meso-diaminopimelic acid in the cell wall peptidoglycan and DNA G + C contents of 36.1-37.1 mol%. The polar lipid pattern of strain XH-63T, selected as the representative strain, consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and a phospholipid and two amino phospholipids of unknown structure. This strain possessed anteiso-C(15:0) and anteiso-C(17:0) as the major fatty acids (altogether representing 72.5% of total) and MK-7 as the major menaquinone. 16S rRNA gene analysis of the three strains showed that they were within the Gracilibacillus cluster, with highest sequence similarity (95.4-95.8%) with Gracilibacillus dipsosauri. Based on a combination of phenotypic, chemotaxonomic and phylogenetic features, it is proposed that the three isolates represent a novel species of the genus Gracilibacillus, Gracilibacillus orientalis sp. nov. The type strain is strain XH-63T (= CCM 7326T = AS 1.4250T = CECT 7097T).

Bacillaceae↗

Halostagnicola larsenii gen. nov., sp. nov., an extremely halophilic archaeon from a saline lake in Inner Mongolia, China.

Strain XH-48(T) was isolated from the sediment of Lake Xilinhot, a saline lake in Inner Mongolia (China). The organism is pleomorphic, neutrophilic and requires at least 2.5 M (15 %) NaCl, but not MgCl(2), for growth; it exhibits optimal growth at 3.4 M (20 %) NaCl. The G+C content of its DNA is 61 mol%. 16S rRNA gene sequence analysis revealed that strain XH-48(T) is a member of the family Halobacteriaceae, but there were low levels of similarity with other members of this family. The highest sequence similarity values (94.5 and 93.3 %) were obtained with the 16S rRNA genes of Natrialba aegyptiaca and Natrialba asiatica, respectively. Polar lipid analyses revealed that strain XH-48(T) contains phosphatidylglycerol and phosphatidylglyceromethylphosphate, derived from both C(20)C(20) and C(20)C(25) glycerol diethers, and two unidentified glycolipids. On the basis of the data obtained, the novel isolate cannot be classified within any recognized genus. Strain XH-48(T) should be placed within a novel genus and species within the family Halobacteriaceae, order Halobacteriales, for which the name Halostagnicola larsenii gen. nov., sp. nov. is proposed. The type strain of Halostagnicola larsenii is strain XH-48(T) (=DSM 17691(T)=CGMCC 1.5338(T)=JCM 13463(T)=CECT 7116(T)).

Aerobiosis↗

Halorubrum orientale sp. nov., a halophilic archaeon isolated from Lake Ejinor, Inner Mongolia, China.

A motile, pleomorphic, red-pigmented archaeon, strain EJ-52T, was isolated from water from Lake Ejinor, a saline lake in Inner Mongolia, China. Analysis of the almost-complete 16S rRNA gene sequence showed that the isolate was phylogenetically related to species of the genus Halorubrum, being most closely related to Halorubrum saccharovorum ATCC 29252T (96.1% sequence similarity), Halorubrum lacusprofundi JCM 8891T (95.9%), Halorubrum tibetense AS 1.3239T (95.2%), Halorubrum alcaliphilum AS 1.3528T (95.2%) and Halorubrum vacuolatum JCM 9060T (95.1%). The polar lipids of strain EJ-52T were C20C20 derivatives of phosphatidylglycerol phosphate and phosphatidylglycerol phosphate methyl ester and a sulfated diglycosyl diether. Strain EJ-52T requires at least 2.5 M NaCl for growth and grows optimally at 3.4 M NaCl. The strain grows at 25-50 degrees C, with optimal growth occurring at 35-45 degrees C. Mg2+ is not required. The DNA G+C content is 64.2 mol%. On the basis of the data obtained in this study, strain EJ52T represents a novel species, for which the name Halorubrum orientale sp. nov. is proposed. The type strain is EJ-52T (=CECT 7145T=JCM 13889T=CGMCC 1.6295T).

Base Composition↗

Natrinema ejinorense sp. nov., isolated from a saline lake in Inner Mongolia, China.

A Gram-negative, non-motile, neutrophilic, pleomorphic and extremely halophilic archaeon, strain EJ-57T, was isolated from saline Lake Ejinor in Inner Mongolia, China. Strain EJ-57T was able to grow at 25-50 degrees C, required at least 1.8 M NaCl for growth (optimum at 3.4 M NaCl) and grew over a pH range from 6.0 to 8.5 (optimum at pH 7.0). Hypotonic treatment with less than 1.5 M NaCl caused cell lysis. Analysis of the almost complete 16S rRNA gene sequence indicated that the isolate represented a member of the genus Natrinema in the family Halobacteriaceae. Strain EJ-57T was most closely related to Natrinema versiforme JCM 10478T (96.2% sequence similarity), Natrinema pallidum NCIMB 777T (95.9% sequence similarity), Natrinema altunense JCM 12890T (95.8% sequence similarity) and Natrinema pellirubrum NCIMB 786T (95.5 % sequence similarity). However, DNA-DNA hybridization experiments showed that strain EJ-57T was not related to these species, with levels of DNA-DNA relatedness equal to or below 39%. The major polar lipids of the isolate were C20C20 and C20C25 derivatives of phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and the disulfated glycolipid S2-DGA-1. The G+C content of the genomic DNA was 64.7 mol%. Comparative analysis of phenotypic characteristics between strain EJ-57T and recognized Natrinema species supported the conclusion that EJ-57T represents a novel species within this genus, for which the name Natrinema ejinorense sp. nov. is proposed. The type strain is EJ-57T (=CECT 7144T=JCM 13890T=CGMCC 1.6202T).

Base Composition↗

Opposite effects of noradrenaline and acetylcholine upon hypocretin/orexin versus melanin concentrating hormone neurons in rat hypothalamic slices.

Hypocretin/orexin (Hcrt/Orx) and melanin concentrating hormone (MCH) are peptides contained in overlapping cell groups of the lateral hypothalamus and commonly involved in regulating sleep-wake states and energy balance, though likely in different ways. To see if these neurons are similarly or differentially modulated by neurotransmitters of the major brainstem arousal systems, the effects of noradrenaline (NA) and carbachol, a cholinergic agonist, were examined on identified Hcrt/Orx and MCH neurons in rat hypothalamic slices. Whereas both agonists depolarized and excited Hcrt/Orx neurons, they both hyperpolarized MCH neurons by direct postsynaptic actions. According to the activity profiles of the noradrenergic locus coeruleus and cholinergic pontomesencephalic neurons across the sleep-waking cycle, the Hcrt/Orx neurons would be excited by NA and acetylcholine (ACh) and thus active during arousal, whereas the MCH neurons would be inhibited by NA and ACh and thus inactive during arousal while disinhibited and possibly active during slow wave sleep. According to the present pharmacological results, Hcrt/Orx neurons may thus stimulate arousal in tandem with other arousal systems, whereas MCH neurons may function in opposition with other arousal systems and thus potentially dampen arousal to promote sleep.

Acetylcholine↗

Gabaergic neurons with alpha2-adrenergic receptors in basal forebrain and preoptic area express c-Fos during sleep.

The basal forebrain (BF) contains cholinergic neurons that stimulate cortical activation during waking. In addition, both the BF and adjacent preoptic area (POA) contain neurons that promote sleep. We examined c-Fos expression in cholinergic and GABAergic neurons in the BF and POA to determine whether they are differentially active following sleep deprivation versus recovery and whether the GABAergic neurons are active during sleep. Whereas the numbers of c-Fos+ cells and proportions of c-Fos+ cells that were cholinergic were decreased, the proportions that were GABAergic were increased following sleep recovery across BF and POA nuclei. Moreover, the sleep-active GABAergic neurons were immunostained for alpha2A-adrenergic receptors. We conclude that GABAergic neurons that commonly bear alpha2-adrenergic receptors comprise sleep-active cells of the BF and POA. These GABAergic cells would be inhibited by noradrenaline (NA) released from locus coeruleus neurons during waking; they would be disinhibited through diminished NA release during drowsiness and thus become active to promote sleep by inhibiting in turn wake-promoting neurons.

Animals↗

A conical piezoelectric transducer with integral sensor as a self-calibrating acoustic emission energy source.

The experimental results of a conical piezoelectric transducer with integral backing sensor as a self-calibrating simulated acoustic emission (SAE) energy source are presented. It has been shown that there is a negative linear relationship between the energy of SAE signal detected by the backing sensor and the relative strength (signal energy) of SAE source in the structure detected by a reference sensor under different transducer-to-structure coupling efficiencies, with AC drives of the same wave packet, frequency and peak amplitude to excite the conical transducer as a SAE source at all the investigated frequencies over the frequency range of interest in AE measurements (nominally from 50 kHz to around 1 MHz). This should enable the relative strength of the SAE source in a structure to be determined using the SAE measurement from the backing sensor for the selected electrical inputs to the conical transducer, and hence to remove the concerns about inconsistent transducer-to-structure coupling affecting the relative strength of the SAE source for calibration.

Journal Article↗

Receiver operating characteristic analysis for the selection of threshold values for detection of capping in powder compression.

The acoustic emission (AE) energy obtained from compressing lactose powder to form pharmaceutical tablets was chosen for condition monitoring of the tablets. The method used was based on the setting of an AE energy decision threshold such that problems of tablet capping and lamination were successfully identified. Capping and lamination are the most common types of problem that can occur in tablets manufacturing using a powder compression process. To assess the performance of a classifier, use was made of a receiver operating characteristic curve (ROC) obtained by plotting the correct detection probability against the false alarm probability based on AE energy distributions for capped and non-capped tablets. The area under the ROC curve, referred to as the AUC, determines the level of competency of the classifier. A value of 0.5 suggests a mere hazarding of guesses whilst a value of 1 indicates correct classification every time. The AE energy approach for tablet capping monitoring gives an AUC value of 0.96, thereby suggesting the possibility of a highly accurate classifier. With the assumption that penalties for false alarm and missed detection are equally severe, using the graphical method of expected penalty cost (EPC), the optimal AE energy decision threshold was established to be 1.2x10(8) units, at which the maximum correct capping detection rate of 95% was achieved. The paper also explains how a decision threshold can be obtained when the two penalties are not equal.

Acoustics↗

Paradoxical REM sleep promoting and permitting neuronal networks.

Since its electrophysiological identification in the 1950's, the state of REMS or PS has been shown through multiple lines of evidence to be generated by neurons in the oral pontine tegmentum. The perpetration of this paradoxical state that combines cortical activation with the most profound behavioral sleep occurs through interplay between PS-promoting (On) and PS-permitting (Off) cell groups in the pons. Cholinergic cells in the LDTg and PPTg promote PS by initiating processes of both forebrain activation and peripheral muscle atonia. Bearing alpha1-adrenergic receptors, cholinergic cells, which likely project to the forebrain, are excited by NA and active during both W and PS (W/PS-On), when they promote cortical activation. Bearing alpha2-adrenergic receptors, other cholinergic cells, which likely project to the brainstem, are inhibited by NA and thus active selectively during PS (PS-On), when they promote muscle atonia. Noradrenergic, together with serotonergic, neurons, as PS-Off neurons, thus permit PS in part by lifting their inhibition upon the cholinergic PS-On cells. The noradrenergic/serotonergic neurons are inhibited in turn by local GABAergic PS-promoting neurons that may be excited by ACh. Other similarly modulated GABAergic neurons located through the brainstem reticular formation become active to participate in the inhibition of reticulo-spinal and raphe-spinal neurons as well as in the direct inhibition of motor neurons. In contrast, a select group of GABAergic neurons located in the oral pontine reticular formation and possibly inhibited by ACh turn off during PS. These GABAergic PS-permitting neurons release from inhibition the neighboring large glutamatergic neurons of the oral pontine reticular formation, which are likely concomitantly excited by ACh. In tandem with the cholinergic neurons, these glutamatergic reticular neurons propagate the paradoxical forebrain activation and peripheral inactivation that characterize PS.

Animals↗

Tepidibacter thalassicus gen. nov., sp. nov., a novel moderately thermophilic, anaerobic, fermentative bacterium from a deep-sea hydrothermal vent.

A moderately thermophilic, anaerobic, endospore-forming bacterium (strain SC 562T) was isolated from a hydrothermal vent chimney located at 13 degrees N on the East-Pacific Rise at a depth of 2650 m. Cells of strain SC 562T were straight to slightly curved rods, which were 0.7-0.9 microm in diameter and 3.5-6.0 microm in length with peritrichous flagella. Strain SC 562T formed round, refractile endospores in terminally swollen sporangia. The temperature range for growth was 33-60 degrees C, with an optimum at 50 degrees C. The pH range for growth was 4.8-8.5, with an optimum at pH 6.5-6.8. Growth of strain SC 562T was observed at NaCl concentrations ranging from 1.5 to 6% (w/v). The substrates utilized by strain SC 562T included casein, peptone, albumin, yeast extract, beef extract, alanine plus proline and starch. Glucose, maltose, pyruvate, valine and arginine each slightly stimulated growth in the presence of yeast extract. The products of glucose fermentation were ethanol, acetate, H2 and CO2. Strain SC 562T reduced elemental sulfur to hydrogen sulfide. The G + C content of the DNA of strain SC 562T was 24 mol%. 16S rDNA sequence analysis revealed that the isolated organism belonged to cluster XI of the Clostridium subphylum. On the basis of its physiological properties and phylogenetic analyses, it is proposed that strain SC 562T represents the sole species of a novel genus, Tepidibacter; the name Tepidibacter thalassicus is proposed for strain SC 562T (=DSM 15285T=UNIQEM 215T).

Base Composition↗

Immunostaining of cholinergic pontomesencephalic neurons for alpha 1 versus alpha 2 adrenergic receptors suggests different sleep-wake state activities and roles.

Cholinergic neurons of the pontomesencephalic tegmentum play a critical role in paradoxical sleep, when, according to single unit recording of 'possibly' cholinergic neurons, they fire maximally. The profile of activity of the cholinergic neurons may be determined by noradrenergic locus coeruleus neurons that are active during waking and silent during paradoxical sleep. Indeed, a permissive role of the noradrenergic neurons in paradoxical sleep has been proposed based upon an inhibitory action of noradrenaline through alpha(2) adrenergic receptors on the cholinergic cells. Yet some 'possibly' cholinergic neurons are purportedly maximally active during waking and excited by noradrenaline through alpha(1) receptors. In the present study, we examined by fluorescent dual-immunostaining in the laterodorsal and pedunculopontine tegmental nuclei of the rat whether choline acetyltransferase-immunopositive neurons are stained for alpha(2A) or alpha(1A) adrenergic receptors. For comparison, we examined immunostaining for these receptors on tyrosine hydroxylase-immunopositive locus coeruleus neurons, which are known to bear alpha(2A) autoreceptors. Whereas virtually all the noradrenergic neurons were labeled for the alpha(2A) and none for the alpha(1A), approximately half the cholinergic neurons were labeled for the alpha(2A) and one third for the alpha(1A) adrenergic receptors in adjacent sections. These results suggest that different groups of cholinergic neurons bear alpha(2) versus alpha(1) adrenergic receptors and would accordingly have different sleep-wake state activities and roles. The alpha(2)-bearing group would be inhibited by noradrenaline during waking to become disinhibited and maximally active while promoting paradoxical sleep, whereas the alpha(1)-bearing group would be excited by noradrenaline during waking to become maximally active while promoting features of that state.

Animals↗

The filling of powders into two-piece hard capsules.

The factors that influence the filling of powders into hard capsules are reviewed. Powder properties that affect machine performance and influence plug formation are highlighted. The use of instrumented machines and machine simulators in formulation development are described. The properties of excipients that are required for uniform filling are identified. The use of optimisation techniques to produce rational formulations is discussed.

Capsules↗

Cloning and expression of an endocellulase gene from a novel streptomycete isolated from an East African soda lake.

Alkaline cellulase-producing actinomycete strains were isolated from mud samples collected from East African soda lakes. The strains were identified as novel Streptomyces spp. by 16S rDNA sequence analysis. A cellulase gene (cel12A) from Streptomyces sp. strain 11AG8 was cloned by expression screening of a genomic DNA library in Escherichia coli. From the nucleotide sequence of a 1.5-kb DNA fragment, an open reading frame of 1,113 nucleotides was identified encoding a protein of 371 amino acids. From computer analysis of the sequence, it was deduced that the Cel12A mature enzyme is a protein of 340 amino acids. The protein contained a catalytic domain, a glycine-rich linker region, and a cellulose-binding domain of 221, 12, and 107 amino acids, respectively. FASTA analysis of the catalytic domain of Cel12A classified the enzyme as a family 12 endoglucanase and the cellulose-binding domain as a family IIa CBD. Streptomyces rochei EglS was determined as nearest neighbor with a similarity of 75.2% and 61.0% to the catalytic domain and the cellulose-binding domain, respectively. The cell2A gene was subcloned in a Bacillus high-expression vector carrying the Bacillus amyloliquefaciens amylase regulatory sequences, and the construct was transformed to a Bacillus subtilis host strain. Crude enzyme preparations were obtained by ultrafiltration of cultures of the Bacillus subtilis recombinant strain containing the 11AG8 cell2A gene. The enzyme showed carboxymethylcellulase (CMCase) activities over a broad pH range (5-10) with an optimum activity at pH 8 and 50 degrees C. The enzyme retained more than 95% of its activity after incubation for 30 min under these conditions.

Africa, Eastern↗