Intramolecular hydrogen bonding in articaine can be related to superior bone tissue penetration: a molecular dynamics study

Local anesthetics (LAs) are drugs that cause reversible loss of nociception during surgical procedures. Articaine is a commonly used LA in dentistry that has proven to be exceptionally effective in penetrating bone tissue and induce anesthesia on posterior teeth in maxilla and mandibula. In the present study, our aim was to gain a deeper understanding of the penetration of articaine through biological membranes by studying the interactions of articaine with a phospholipid membrane. Our approach involves Langmuir monolayer experiments combined with molecular dynamics simulations. Membrane permeability of LAs can be modulated by pH due to a titratable amine group with a pKa value close to physiological pH. A change in protonation state is thus known to act as a lipophilicity switch in LAs. Our study shows that articaine has an additional unique lipophilicity switch in its ability to form an intramolecular hydrogen bond. We suggest this intramolecular hydrogen bond as a novel and additional solvent-dependent mechanism for modulation of lipophilicity of articaine which may enhance its diffusion through membranes and connective tissue.     

不同胁迫预处理提高水稻幼苗抗寒性期间蛋白质的变化

水稻(Oryza sativa L.)幼苗经盐、热激和冷三种不同胁迫预处理均提高了幼苗的抗寒性。与未预处理苗相比,在处理后、低温伤害后和常温下恢复2d的三个时期,不同胁迫预处理苗的可溶性和热不稳定蛋白含量变化趋势甚为相似,但热稳定蛋白含量变化则各有异同。SDS-PAGE图谱分析显示,不同胁迫预处理提高水稻幼苗抗寒性时,其可溶性蛋白、热稳定和热不稳定蛋白组成变化亦各有异同。除诱导出共有的新多肽外,还各自诱导出特有的新多肽。结果表明,植物对不同胁迫的交叉适应存在一定的共同机理,但亦可看出植物对同一种环境胁迫似乎不是以同一的机理去适应。     

Mineralization of the sulfonated azo dye Mordant Yellow 3 by a 6-aminonaphthalene-2-sulfonate-degrading bacterial consortium.

Under anaerobic conditions the sulfonated azo dye Mordant Yellow 3 was reduced by the biomass of a bacterial consortium grown aerobically with 6-aminonaphthalene-2-sulfonic acid. Stoichiometric amounts of the aromatic amines 6-aminonaphthalene-2-sulfonate and 5-aminosalicylate were generated and excreted into the medium. After re-aeration of the culture, these amines were mineralized by different members of the bacterial culture. Thus, total degradation of a sulfonated azo dye was achieved by using an alternating anaerobic-aerobic treatment. The ability of the mixed bacterial culture to reduce the azo dye was correlated with the presence of strain BN6, which possessed the ability to oxidize various naphthalenesulfonic acids. It is suggested that strain BN6 has a transport system for naphthalenesulfonic acids which also catalyzes uptake of sulfonated azo dyes. These dyes are then gratuitously reduced in the cytoplasm by unspecific reductases.     

Thyroliberin receptor binding and adenylyl cyclase activation in cultured prolactin-producing rat pituitary tumor cells (GH cells)

A thyroliberin (TRH)-responsive particulate bound adenylyl cyclase is present in two rat anterior pituitary tumor cell strains (GH4C1 and GH3) which synthesize and secrete prolactin. At a given Mg2+ concentration, ATP and the guanyl nucleotides GTP and guanyl 5'-yl-imidodiphosphate (GMP-P(NH)P) caused a dose-dependent increase in adenylyl cyclase activity. The maximum response to thyroliberin occurred with ATP and GTP at concentrations above 0.30 mM and 2 microM, respectively. The maximal stimulatory effect of thyroliberin on adenylyl cyclase activity was 2-fold in the presence of GTP. GMP-P(NH)P increased the basal enzyme activity 4- to 10-fold over and above that of equimolar concentrations of GTP but supported poorly the TRH-induced response. Mg2+ caused a dose-dependent increase in the basal enzyme activity and reduced TRH and fluoride-induced responses. Also, Mn2+ and Co2+ stimulated the basal adenylyl cyclase activity while Zn2+, Ca2+, and Cu2+ inhibited the enzyme, and neither cations supported the TRH response. Half-maximal stimulation of the adenylyl cyclase by TRH and half-maximum binding of [3H]TRH to membranes at 35 degrees C were 102 and 56 nM, respectively. Pretreatment with TRH decreased the apparent Vmax of the enzyme and the maximal binding of [3H]TRH. Of 6 TRH analogs tested, only one was able to displace [3H]TRH from its receptor and to increase the adenylyl cyclase activity. We suggest that adenylyl cyclase activation is an early event in the stimulus secretion coupling between TRH and prolactin-producing GH cells.     

Uronic acid sequence in alginate from different sources

Alginate may be considered as a block co-polymer of D-mannuronic and L-guluronic acids, and consists of three types of blocks: homopolymeric blocks of mannuronic acid (MM) and of guluronic acid (GG), and blocks with an alternating sequence (MG). The block composition of alginates has been characterized by a simple chemical method involving partial hydrolysis with acid, followed by fractional precipitation of the acid-resistant part of the alginate. Alginates from eleven different species of brown algae have been examined and, for five species, alginates from different tissues have been compared. The results indicate that young tissue is rich in MM blocks, and that the difference between the alginates from different species is mainly due to the alginates from the older parts of the plants. Extracellular alginates from two types of bacteria have been examined.     

Effects of hypersecretion of growth hormone and prolactin on plasma levels of glucagon and insulin in GH3-cell-tumor-bearing rats, and the influence of bromocriptine treatment

Plasma levels of prolactin, growth hormone, glucagon insulin and glucose were measured in non-treated control rats, bromocriptine-treated control rats and GH3-cell-tumor-bearing rats with and without bromocriptine treatment. Bromocriptine treatment increased plasma levels of glucagon, insulin and glucose in control rats. Tumor-bearing rats had increased body weight and increased plasma levels of prolactin, growth hormone, glucagon, insulin and glucose. Bromocriptine treatment reduced body weight and decreased the plasma levels of prolactin, glucagon and insulin, as compared to non-treated tumor-bearing rats. The drug had no effect on plasma levels of growth hormone and glucose. These results indicate that, in GH3-cell-tumor-bearing rats, prolactin, glucagon and insulin are more sensitive to the action of bromocriptine than growth hormone.     

Die Epiphyse und die circumventrikulären Strukturen des Epithalamus im Gehirn des Elefanten (Loxodonta africana)

Zusammenfassung Die dorsale Wand des Epithalamus des Elefanten enthält zwei Aussackungen, den langen Recessus suprapinealis (RS), der mit Plexus chorioideus gefüllt ist, und den kurzen breiten Recessus pinealis (RP). Die dickeren Wandpartien beider Recessus bestehen überwiegend aus Pinealgewebe mit Pinealocyten.Das Ependym des Epithalamus bildet an fünf Orten circumventrikuläre Strukturen (CS); drei dieser CS gehören zum Subcommissuralorgan. Das Ependym mit der höchsten Aktivität liegt auf der unteren Lippe und in den spitzen lateralen Hörnern des RP. Dieses Epithel trägt Kinocilien und besitzt Zellprotrusionen; es ist mäßig gomoripositiv. Über die Verteilung der verschiedenen Kennzeichen der CS-Strukturen gibt eine Tabelle Auskunft.In der lateralen Wand des Epithalamus unter der Commissura habenularis liegen die Verrucae epithalami, die unterschiedlich tiefe ependymbedeckte Spalten besitzen. Die mögliche funktionelle Bedeutung dieser Strukturen wird kurz erörtert.

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The epiphysis and the circumventricular structures of the epithalamus in the brain of the elephant (Loxodonta africana)

Summary The dorsal wall of the epithalamus of the elephant has two evaginations: the long recessus suprapinealis (RS) filled with plexus chorioideus and the short and wide recessus pinealis (RP). The thick part of the wall of both recessus consists mainly of pineal tissue with pinealocytes.The ependyma of the epithalamic region has about 5 loci with circumventricular formations (CS), three of them belonging to the subcommissural organ. The ependyma with equivalents of high activity is situated in the lower lip and in the lateral tapering corners of the RP. This epithelium bears kinocilia and shows protrusions of the cells extending into the ventricle, it is fairly gomoripositive. Details concerning the structural differences in the various loci of CS are described.There are some verrucae epithalami in the lateral wall of the epithalamus below the commissura habenularis having more or less deep clefts covered with ependyma. The possible functions of these structures are briefly discussed.

Mit dankenswerter Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Die Membrana limitans gliae superficialis der Sehrinde der Katze

Zusammenfassung Die Membrana gliae limitans superficialis im Cortex des Gehirns der Katze ist an den Kuppen dünner (herab bis 3 m) als an den Windungstälern (bis zu 15 m). Sie enthält drei verschiedene Fortsätze der Astrocyten, deren Perikarya an der Grenze zum eigentlichen Neuropil der Molekularschicht liegen. Es handelt sich um: 1. Runde oder ovale Fortsätze mit dicht gepackten Gliafilamenten, die horizontal, schräg oder radiär verlaufen. 2. Flache, oberflächliche Fortsätze mit Filamenten (Endfüße). 3. Astrocytenlamellen, d.h. sehr platte, horizontal liegende Fortsätze ohne Filamente, die stapelförmig aufeinanderliegen. Eine specific junction wird beschrieben.

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The membrana limitans gliae superficialis of cat's visual cortex

Summary In the region of the sulci of the cats brain the membrana limitans gliae superficialis is thicker (up to 15 m) than in the gyri (down to 3 m). It contains 3 different kinds of processes of astrocytes. Its pericarya are situated at the border of the neuropil. The different kinds of processes are: 1. round or oval processes with closely packed filaments of the glia having a horizontal, oblique or radiate direction, 2. flat, superficial processes with filaments (end-feet of the glia), 3. astrocytic lamellae = very flat processes without filaments lying horizontally, piled up between the processes with filaments. A specific junction is described.

Herrn Prof. Dr. Alkmar v. Kügelgen zum 60. Geburtstag gewidmet. — Mit dankenswerter Unterstützung durch die Deutsche Forschungsgemeinschaft. — Für technische Hilfe danke ich Frau H. Prien.     

Die Länge der Internodien der Markfasern im Bereich der Sehrinde der erwachsenen Katze

Zusammenfassung Die Internodienlänge der Markfasern und ihre Abhängigkeit vom Durchmesser wird durch indirekte Messungen an elektronenmikroskopischen Bildern bestimmt. Der Ranviersche Schnürring wird für die Messung in einen nackten und zwei lamellierte Teile unterteilt (Abb. 1). Die Summenlänge der Markfasern und der Nodien besitzen die in Abb. 4 sichtbare Beziehung zum Durchmesser. Die Internodienlänge beträgt für Markfasern mit einem Durchmesser von 0,4 etwa 40 für solche mit einem Durchmesser von 2,5 etwa 500 . Es wurde eine mittlere Internodienlänge von 90 gefunden. Die Länge aller Markfasern pro mm³ beträgt 590 m; daraus kann eine Anzahl von 6 bis 7 Millionen Ranvierscher Schnürringe pro mm³ errechnet werden. Die Internodienlänge und der Durchmesser stehen wahrscheinlich in einer logarithmischen Beziehung (Abb. 8). In diese logarithmische Beziehung fügen sich die Ergebnisse anderer Autoren gut ein.

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Summary In electron micrographs the internodal length of myelinated fibers and its relation to the diameter has been measured. In this investigation the node of Ranvier is subdivided in three parts, i. e. one non-myelinated and two lamellated parts (Fig. 1). The relationship between the length of the nodes of Ranvier and its diameter is determined (Fig. 4). The internodal length is about 40 for fibers with a diameter of 0.4 and 500 for those with a diameter of 2.5 . The average internodal length is about 90 . The myelinated fibers have a total length of 590 m per mm³; in one mm³ there are therefore 6 to 7 million nodes. The relation between length of internodium and diameter of fiber is probably logarithmic (Fig. 8). The results are compared with similar measurements on peripheral nerves carried out by other authors.

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Mit dankenswerter Unterstützung durch die Deutsche Forschungsgemeinschaft.