The interaction between Eu(III) ion and different pH buffers, popular in biology and biochemistry, viz. HEPES, PIPES, MES, MOPS, and TRIS, has been studied by solution nuclear magnetic resonance spectroscopy (NMR) and time-resolved laser-induced fluorescence spectroscopy (TRLFS) techniques. The Good\'s buffers reveal non-negligible interaction with Eu(III) as determined from their complex stability constants, where the sites of interaction are the morpholine and piperazine nitrogen atoms, respectively. In contrast, TRIS buffer shows practically no affinity towards Eu(III). Therefore, when investigating lanthanides, TRIS buffer should be preferred over Good\'s buffers.

Various drugs are known to cause pill esophagitis. Antimicrobial drugs and nonsteroidal anti-inflammatory drugs are the most common causes of pill-induced esophagitis. Most patients suffer only self-limiting pain, but serious complications can occur. A 21-year-old man was admitted to our outpatient clinic with retrosternal chest pain, dysphagia, and odynophagia complaints, which occurred within 2 weeks after starting dexketoprofen trometamol. An upper endoscopy system examination revealed three well-demarcated ulcers in the esophagus at 35 cm from the incisors. Dexketoprofen trometamol may cause esophageal lesions. This rare disorder should be considered in patients presenting with sudden-onset retrosternal pain in addition to dysphagia and odynophagia.

OBJECTIVE: Adequate pain management following day-case surgery allows early ambulation of patients. In this study, we aimed to compare postoperative analgesic efficacy of intravenous (iv) dexketoprofen vs. iv paracetamol following day-case operative hysteroscopy.
METHODS: One hundred and fourteen American Society of Anesthesiologists (ASA) I-II patients scheduled for day-case operative hysteroscopy were recruited and randomized to three groups in the study. Group D received 50 mg iv dexketoprofen trometamol, Group P 1000 mg iv paracetamol and Group C normal saline solution. Visual Analogue Scale (VAS) pain intensity, pain relief, sedation, nausea-vomiting, other side effects, and additional opioid analgesic requirement were noted at postoperative 15 minutes (min), 30 min, 1 hour (h), 2 h, and 3 h. Patients with VAS>=40 mm received meperidine 0.25 mg/kg as rescue analgesic medication.
RESULTS: VAS scores at 15 min, 30 min, 1 h, and 2 h were significantly lower in Group D compared to Group C. VAS scores at 15 min and 30 min were significantly lower in Group D compared to Group P. The percentages of patients who required opioid treatment were 34%, 60%, and 63% in Groups D, P and C, respectively (p<0.05). Total delivered opioid dose was 0.10±0.16 mg/kg, 027±0.33 mg/kg and 0.28±0.25 mg/kg in Groups D, P and C, respectively (p<0.05). Pain relief score was significantly better in Group D at postoperative 15 min when compared with Group C (p<0.05).
CONCLUSIONS: Our study demonstrated that iv dexketoprofen has superior efficacy for postoperative pain management following day-case operative hysteroscopy when compared with paracetamol and placebo.

Selection of suitable buffer types is often a crucial step for generating appropriate protein samples for NMR and x-ray crystallographic studies. Although the possible interaction between MES buffer (2-(N-morpholino)ethanesulfonic acid) and proteins has been discussed previously, the interaction is usually thought to have no significant effects on the structures of proteins. In this study, we demonstrate the direct, albeit weak, interaction between MES and human liver fatty acid binding protein (hLFABP). Rather than affecting the structure of hLFABP, we found that the dynamics of hLFABP, which were previously proposed to be relevant to its functions, were significantly affected by the binding of hLFABP with MES. Buffer interference with protein dynamics was also demonstrated with Bis-Tris buffer, which is quite different from MES and fatty acids in terms of their molecular structures and properties. This result, to our knowledge, is the first published report on buffer interference with protein dynamics on a microsecond to millisecond timescale and could represent a generic problem in the studies of functionally relevant protein dynamics. Although being a fortuity, our finding of buffer-induced changes in protein dynamics offers a clue to how hLFABP accommodates its ligands.

BACKGROUND: Lactic acidosis is a rare, yet life-threatening adverse drug effect of highly active antiretroviral therapy (HAART), specifically stavudine and lamivudine. These nucleoside analogue reverse transcriptase inhibitors (NRTIs) are commonly used to treat patients infected with the human immunodeficiency virus (HIV).
METHODS: We report the use of Tris-hydroxymethyl aminomethane (THAM) to treat severe lactic acidosis due to HAART in a 50-year-old African-American woman. NRTIs can cause hyperlactinaemia by interfering with mitochondrial oxidative phosphorylation function, which normally removes H(+) generated by the hydrolysis of adenosine triphosphate. This side-effect is associated with a high mortality in patients infected with HIV. One explanation for this high mortality is that lactic acidosis is typically refractory to treatment with commonly used buffering agents.
CONCLUSIONS: THAM generates serum bicarbonate, and reduces the level of carbon dioxide in arterial blood. Both of these qualities appear to make THAM an ideal agent for treating lactic acidosis caused by HAART.

Two widely used biological buffers [tris(hydroxymethyl)aminomethane (TRIS) and phosphate] covalently react with the topoisomerase II inhibitor clerocidin, affecting the drug\'s reactivity profile. Comprehensive analytical and structural analysis obtained by LC/MS, MS/MS, NMR, and IR techniques shows that these buffers form reversible and irreversible adducts through reactions with chemical groups, such as carbonyls, aldehydes, and epoxide. Analysis of the kinetic data on adducts formation suggests two parallel mechanisms for the inhibition of drug activity. The first involves modulation of the reactivity of the epoxide group obtained by elimination of the spiro system and relief of ring strain. This effect does not abolish epoxide reactivity and is more evident for the TRIS adduct, which can count on intramolecular stabilization of the form devoid of the spiro system. The second mechanism involves the slow nucleophilic attack to the epoxide ring, which results in permanent deactivation of the functional group responsible for topoisomerase II inhibition. This effect is predominant in phosphate buffer and is more evident for longer reaction times. These results provide a compelling reminder that the activity of chemically complex drugs in biological systems can be severely altered by buffer interactions, which may not be immediately predictable from the identity of the active group(s) and may require a more detailed knowledge of the subtle effects induced by vicinal groups.

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Peptic ulcers, perforations, and serious gastrointestinal bleeding have not been reported with intramuscular ketoralac tromethamine, the first parenteral nonsteroidal anti-inflammatory drug available for analgesic use. This article presents the case of a 39-year-old black female who underwent surgical repair of a perforated gastric ulcer after receiving multiple dosages of intramuscular ketoralac tromethamine in the emergency room over a period of 21/2 months for the treatment of pain due to chronic pancreatitis.

The nephrotoxic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are well recognized. Known potentiating risk factors include pre-existing renal disease, intravascular volume depletion, and concomitant administration of other nephrotoxic drugs. We present a case report of renal failure following short term usage of intramuscular ketorolac (Toradol) in a patient with no known risk factors who underwent an uncomplicated laparotomy. The literature concerning ketorolac-induced renal failure is reviewed and physicians are reminded to be aware of this potential complication.