Mechanisms linking hypertriglyceridemia to acute pancreatitis

Hypertriglyceridemia (HTG) is a metabolic disorder, defined when serum or plasma triglyceride concentration (seTG) is >1.7 mM. HTG can be categorized as mild to very severe groups based on the seTG value. The risk of acute pancreatitis (AP), a serious disease with high mortality and without specific therapy, increases with the degree of HTG. Furthermore, even mild or moderate HTG aggravates AP initiated by other important etiological factors, including alcohol or bile stone. This review briefly summarizes the pathophysiology of HTG, the epidemiology of HTG-induced AP and the clinically observed effects of HTG on the outcomes of AP. Our main focus is to discuss the pathophysiological mechanisms linking HTG to AP. HTG is accompanied by an increased serum fatty acid (FA) concentration, and experimental results have demonstrated that these FAs have the most prominent role in causing the consequences of HTG during AP. FAs inhibit mitochondrial complexes in pancreatic acinar cells, induce pathological elevation of intracellular Ca2+ concentration, cytokine release and tissue injury, and reduce the function of pancreatic ducts. Furthermore, high FA concentrations can induce respiratory, kidney, and cardiovascular failure in AP. All these effects may contribute to the observed increased AP severity and frequent organ failure in patients. Importantly, experimental results suggest that the reduction of FA production by lipase inhibitors can open up new therapeutic options of AP. Overall, investigating the pathophysiology of HTG-induced AP or AP in the presence of HTG and determining possible treatments are needed

Az o-krezolftaleinfoszfáttal végrehajtott lúgos foszfatáz próba a FIL-IDF 63:1971 tükrében III.

Die Verfasser synthetisierten die durch sie modellisierte und geplante Verbindung: o-Kresolphthaleinphosphat. Vergleichende Untersuchungen ermöglichten die Feststellung der Bewertbarkeit der Reaktions von o-Kresolphthalein-Lauge und Phenol i Phenol-2,6-dibromchinonchlorimid, Phenol-4-aminoantipyrin, Phenol-Folin) auf Grund der durch F IL -ID F 63:1971 vorgeschriebenen Aktivitätsmessung und auf Grund der Empfehlung der ungarischen Norm MSZ 9619/2, der objektiven Farbenmessung von CIE 1976. Auf Grund dieser Vergleichung wurde festgestellt, dass auch unter den von F IL -ID F 63:1971 vorgeschrieben Umständen die Kombination o-kresolphthaleinLauge die sogar mit freiem Auge am besten wahrnehmbare Reaktion bei der alkalischen Phosphataseprobe ergibt. Ein weiterer Vorteil dieser Probe ist, dass sie keine Vorbereitung und kein Instrument erfordert, und eine mit der von F IL -ID F 63:1971 vorgeschriebenen Probe gleichwertige optimierte Methode darstellt, die auch unter Betriebsumständen gut anwendbar ist. Der Zeitaufwand dieser Methode ist statt 30 minuten nur 13,5 Minuten (20, 21). The authors synthesized o-cresol phthalein phosphate modelled and eveloped by them. Comparisons were carried out in order to establish the suitability for evaluation of the reactions of o-cresol phthalein-alkali and phenol (phenol-2 ,6 - dibromoquinone-chloroimide, phenol-4-aminoantipyrin, phenol-Folin) ony the basis of the measurement of activity prescribed by F IL -ID F 63:1971 and of the Hungarian standard MSZ 9619/2, of the objective colour measuring procedure suggested by C1E in 1976. On the basis of comparison tests it was found that even under the conditions prescribed by F IL -ID F 63:1971 o-cresol phthalein alkali gives at the alkaline phosphatase test the reaction which can be best evaluated even by the naked eye. A further advantage of the test is that it represents an optimized method equivalent to that prescribed by F IL -ID F 63:1971 and that it can be used also under conditions prevailing in plants. Its time requirement is 13.5 minutes instead of 30 minutes (2 0 , 2 1 )

Izolált enzimmel végrehajtott lúgos foszfatáz próba és létjogosultsága IV.

Die mit dem zum ursprünglichen Volum der Milch wiederhergestellten isolierten Enzym durchgeführte alkalische Phosphataseprobe mit o-Kresolphthaleinphosphat war bewertbarer als die des parallel mit Naturmilch durchgeführten Musterelementes. Die bei der Objektiven Farbenmessung der mit dem isolierten Enzym durchgeführten Reaktionen erhaltenen AE*ah-'Werte sind immer und auf eine signifikante Weise höher. Die amtliche Anwendung dieser Methode wurde trotzdem durch das Normungskomitee der Milchindustrie abgelehnt, weil die Probe trotz ihrer empfindlicheren negativen Ergebnisse die Tuberkulosebakterien der Milchenthalten kann. Nach der Meinung des Normungskomitees der Milchindustrie soll man die zur Herstellung der Säuglingsmilch und Schülermilch dienende Milch sorgfältig auswählen. Zur Ergänzung dieses Wahlvorganges wird die von der Verfassern schon früher angewandte, auch in der Milch nachweisbare Abwehrfermentreaktion empfohlen

Tej és egyes tejtermékek lúgos foszfatáz próbájának változatai

Auf Grund der Untersuchung von verschiedenen Varianten der bisher angewendeten ungarischen raschen Phosphataseprobe (5) und der nach der sowjetischen Norm vorgeschriebenen Phosphataseprobe wird zur Untersuchung von Milch und Sahne ein in 100 cm3 4 g Ammoniumchlorid und 34,8 cm3 25% Ammoniumhydroxid, ferner 1 g Hydrogen-Phenolphthaleinphosphat enthaltendes Reagens als geeignetste betrachtet. Zur Phosphataseprobe von Molkereiprodukten (Rahm, Kefir, saure Milch, Cremequark) wird ein Reagens empfohlen, das den vorangehend angegebenen Puffer in einer zehnfachen Verdünnung enthält. Die Inkubationsperiode beträgt bei 3 8 -4 0 °C 20 Minuten bzw. 2 Stunden. Die in den Reaktionsgemischen durchgeführten objektiven Farbmessungen, die noch fortgesetzt werden, unterstützten die oben empfohlenen optimalen Veränderungen. On investigating the variants of the Hungarian quick phosphatase test applied so far (5) and of the phosphatase test specified in the Soviet standard (8 ) the reagent containing in 100 cm3 4 g of ammonium chloride and 34.8 cm3 of 25% ammonium hydroxide, further 1 g of hydrogen-phenolphthalein-phosphate proved to be the most suitable for the investigation of milk and cream. For the phosphatase test of dairy products (such as sour cream, kefir, sour milk, creamcurd) a reagent containing the above specified buffer in a tenfold dilution is suggested. The incubation period is at 38 — 40 °C 20 minutes and 2 hours, respectively. Objective colour measurements carried out in reaction mixtures which measurements are still in progress, supported the optimum alterations suggested above

A tej lúgos foszfatáz próbáinak összehasonlítása a színmérés tükrében II.

Als Fortsetzung früherer Untersuchungen wurden die optimalen Umstände der alkalischen Phosphatasereaktion weiter studiert. Zur Feststellung der Farbe ein Tristimulus-Colorimeter vom MOM-COLOR-S-Typ verwendet, die Auswahl der best geeigneten Variante der Probe, des zur Untersuchung angewendeten Puffers und des Substrats auf Grund des OE*b-Wertes ermöglicht. Unter den selben Umständen ergab eine mit einem Ammoniumchlorid (40g/ 1000 cm3) und Ammoniumhydroxid (348 cm3 25% NH4OH in 1000 cm3) enthaltenden Puffer und mit zur Zeit als Modell zur Verfügung stehenden o-Cresolphthaleinphosphat durchgeführte Untersuchung die bestens auswertbare Reaktion. Die angewendeten Mengen waren: 5 cm3 Milch, 0,2 cm3 der Substrat/Pufferlösung (1 g/100 cm3) und nach einer Inkubation für 20 Minuten bei einer Temperatur von 38 °C 0,2 cm3 einer 2,5n Natriumhydroxidlösung zur Farbenbildung. In continuation of their earlier investigations the optimum conditions of the alkaline phosphatase test were studied. A tristiinuls colorimeter of MOM-COLOR-S type was used for the colour measurement. This instrument ensures, on the basis of the value AE*b, the choice of the most suitable variants of the sample, of the applied buffers and of the substrates. Under identical conditions the best evaluable reaction was obtained with the use of a buffer containing ammonium chloride (40 g in 1000 cm3) and ammonium hydroxide (348 cm3 of 25% NH4OH in 1000 cm3), carried out with o-cresolpihthalein phosphate which latter exists at present in form of a model. The amount of substances required for test is 5 cm3 of milk, and 0,2 cm3 of the substrate/buffer solution (containing 1 g of substrate in 100 cm3 of buffer), and after incubation for 20 minutes at 38 °C 0,2 cm3 of a 2,5 N solution of sodium hydroxide

Preparation and investigation of mefenamic acid-polyethylene glycol-sucrose ester solid dispersions

Mefenamic acid (MA) is a widely used non-steroidal anti-inflammatory (NSAID) drug. The adverse effects typical of NSAIDs are also present in the case of MA, partly due to its low water solubility. The aim of this study was to increase the water solubility of MA in order to influence its absorption and bioavailability. Solid dispersions of MA were prepared by the melting method using polyethylene glycol 6000 and different types (laurate, D-1216; palmitate, P-1670; stearate, S-1670) and amounts of sucrose esters as carriers. The X-ray diffraction results show that MA crystals were not present in the products. Dissolution tests carried out in artificial intestinal juice showed that the product containing 10 % D-1216 increased water solubility about 3 times. The apparent permeability coefficient of MA across human Caco-2 intestinal epithelial cell layers was high and, despite the difference in solubility, there was no further increase in drug penetration in the presence of the applied additives

Determination of glutamate and gaba from rat central nervous system samples with HPLC utilizing fluorescent detection

The research of neurological diseases has great importance and the determination of neurotransmitter concentrations is essential during these investigations. The levels of main excitatory (glutamate) and inhibitory (γ-amino-butyric acid (GABA)) neurotransmitters often change as a result of pathological alterations. For example, in case of migraine, elevated glutamate release is suggested to be a part of the pathomechanism, causing hypersensitivity to pain. Our goal in this study was to optimize a liquid chromatography method to measure glutamate and GABA from the trigeminal nucleus pars caudalis (TNC) of rats, which is responsible for pain processing. As a result, we were able to validate our method according to international guidelines where the investigated parameters were LOD, LOQ, precision and recovery. Furthermore, we applied a new internal standard which has not been published so far. This method will be utilized in the investigation of migraine animal models to evaluate potential new therapeutic approaches

High-performance liquid chromatographic study on the enantioseparation of fluorine containing cyclic amino acid derivatives

The stereoisomers of several fluorinated cyclic β 3 -amino acid derivatives and their nonfluorinated counterparts were separated on chiral stationary phases containing as chiral selectors cellulose tris-(3,5-dimethylphenyl carbamate), cellulose tris-(3-chloro-4-methylphenyl carbamate), cellulose tris-(4-methylbenzoate), cellulose tris-(4-chloro-3-methylphenyl carbamate), amylose tris-(3,5-dimethylphenyl carbamate) or amylose tris-(5-chloro-2-methylphenyl carbamate). The enantioseparations were carried out in normal-phase mode with n-hexane/alcohol/alkylamine mobile phases in the temperature range 5–40 °C. The effects of the mobile phase composition, the nature and concentration of the alcohol and alkylamine additives, the structures of the analytes and temperature on the separations were investigated