Dopamine: Acid-base properties and membrane penetration capacity.

Dopamine and 4 related compounds were studied by H NMR-pH titrations and a case-tailored evaluation method. The resulting acid-base properties of dopamine are quantified in terms of 3 macroscopic and 12 microscopic protonation constants and the concomitant 3 interactivity parameters. The species- and site-specific basicities are interpreted by means of inductive and shielding effects through various intra- and intermolecular comparisons.

Metal transport capabilities of anticancer copper chelators.

In the present study, several Cu chelators [2,2'-biquinoline, 8-hydroxiquinoline (oxine), ammonium pyrrolidinedithiocarbamate (APDTC), Dp44mT, dithizone, neocuproine] were used to study Cu uptake, depletion and localization in different cancer cell lines. To better understand the concentration dependent fluctuations in the Cu intracellular metal content and Cu-dependent in vitro antiproliferative data, the conditional stability constants of the Cu complex species of the investigated ligands were calculated. Each investigated chelator increased the intracellular Cu content on HT-29 cells causing Cu accumulation depending on the amount of the free Cu(II).

Biorelevant physicochemical profiling of (E)- and (Z)-resveratrol determined from isomeric mixtures.

Biorelevant, isomer-specific physicochemical parameters of resveratrol, a multifunctional component in red wines, with cardioprotective, anti-Alzheimer and several other pharmacologic activities were determined. The parameters include site-specific basicities, lipophilicities, solubilities and diffusion constants for the two geometric isomers. The protonation equilibria of (E)- and (Z)-resveratrol were monitored by H NMR-pH titrations.

Site- and species-specific hydrolysis rates of heroin.

The hydroxide-catalyzed non-enzymatic, simultaneous and consecutive hydrolyses of diacetylmorphine (DAM, heroin) are quantified in terms of 10 site- and species-specific rate constants in connection with also 10 site- and species-specific acid-base equilibrium constants, comprising all the 12 coexisting species in solution. This characterization involves the major and minor decomposition pathways via 6-acetylmorphine and 3-acetylmorphine, respectively, and morphine, the final product. Hydrolysis has been found to be 18-120 times faster at site 3 than at site 6, depending on the status of the amino group and the rest of the molecule.

[The pharmaceutical chemistry of azole antifungals.].

Azole antifungals are a group of compounds that play essential rule in the treatment of surface and deep mycoses. They can be used externally to treat fungal infections of skin, mucous membranes and external genitalia but they are also suitable for oral treatment of systemic mycoses. Structurally they are classified into two groups: imidazoles and triazoles.

The complete microspeciation of ovothiol A disulfide: a hexabasic symmetric biomolecule.

The site-specific acid-base properties of ovothiol A disulfide (OvSSOv), the smallest hexabasic multifunctional biomolecule with complex interdependent moieties, were studied with (1)H NMR-pH and potentiometric titrations. The unprecedented complexity of the protonation microequilibria could be overcome by taking into account the mirror-image molecular symmetry, synthesizing and studying auxiliary model compounds and developing a custom-tailored evaluation method. The amino, imidazole, and carboxylate moieties are quantified in terms of 192 microscopic protonation constants and 64 microspecies, 96 and 36 of which are chemically different ones, respectively.

[Resveratrol in Pharmaceutical Chemistry].

Resveratrol is a polyphenol that can be found in various plants, including grapes. Wines therefore also contain this compound. The famous phenomenon, named "French paradox" is considered to be an effect of resveratrol: the regular, modest consumption of red wine causes low incidence of cardiovascular diseases.

The complete microspeciation of ovothiol A, the smallest octafarious antioxidant biomolecule.

Ovothiol A, a small biomolecule with highly potent antioxidant capacity, and three newly synthesized derivatives were studied by (1)H NMR, (15)N NMR, UV-pH titrations, and a customized evaluation method. The omni-interactive imidazole, amino, carboxylate, and thiolate moieties of ovothiol A are quantified in terms of 32 microscopic protonation constants, the relative concentrations of 16 microspecies, 6 pairwise interactivity parameters, and 8 protonation shifts. The highest and lowest imidazole basicities differ by a record-breaking five orders of magnitude, and the predominant thiolate protonation constant is by far the smallest known thiolate logK value.

Complex forming competition and in-vitro toxicity studies on the applicability of di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) as a metal chelator.

Di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) is a potential candidate in chelation therapy as an iron chelator. This study showed that a combined treatment with 2μM easily available Fe(II), Cu(II) and Zn(II) each and 5μM Dp44mT on eight different cancer cell lines resulted in a 10-40-fold increase in the intracellular Cu content compared to control samples. The uptake of Cu and Cu-dependent cytotoxicity strictly depend on the Cu concentration of the culture medium.

NMR analysis and site-specific protonation constants of streptomycin.

Streptomycin, the classical aminoglycoside antibiotic, generally considered the most basic drug compound was characterized in terms of protonation macro- and microconstants. ¹H NMR-pH and ¹H-¹³C HSQC-pH titrations were carried out on streptomycin and streptidine, a symmetrical constituent compound of reduced complexity to monitor the proton-binding processes of the basic sites. Accurate, undistorted, electrodeless pH measurement was ensured by a new set of in tube indicators.

Electrodeless, accurate pH determination in highly basic media using a new set of (1)H NMR pH indicators.

A set of indicator molecules was selected and applied to elaborate an NMR-based pH determination method, free of glass electrode errors in highly basic media. Accurate measurement of pH values and protonation constants was achieved by a successive build-up of overlapping, increasingly high pH solutions, using a collection of 8 compounds of appropriately incremented basicities. In order to verify the method, acid-base properties were quantified for two compounds with very high basicities in conflicting reports: two pharmaceutically important biguanidine drugs, metformin and phenformin.

The complete microspeciation of arginine and citrulline.

(1)H NMR-pH titrations of arginine, the most basic natural amino acid and citrulline, its neutral counterpart were carried out. Two other closely related auxiliary compounds were also studied. The 8 macroscopic protonation constants were determined.

NMR analysis, protonation equilibria and decomposition kinetics of tolperisone.

The rate constants of spontaneous and hydroxide-catalyzed decomposition and the tautomer-specific protonation constants of tolperisone, a classical muscle relaxant were determined. A solution NMR method without any separation techniques was elaborated to quantitate the progress of decomposition. All the rate and equilibrium constants were determined at four different temperatures and the activation parameters were calculated.

Successful treatment of a septic aneurysm due to Salmonella enteritidis complicated by the rupture of the pelvis of the kidney.

We report on a 43-year-old patient with septic aneurysm complicated by rupture of the pelvis of the kidney due to Salmonella enteritidis that we treated successfully by empiric therapy, then targeted antibiotic therapy and late surgical intervention with iliofemoral crossover bypass grafting and aneurysm resection. The course was complicated by deep neutropenia and chronic hepatitis C infection.

[Rare case of duplex colon invagination].

Authors recite the records of a patient (26) with a 3-year history of dubious abdominal complaints and subileus resulting in numerous examinations and surgical observations, with the diagnosis of lower abdominal pain of unknown origin. He was acutely admitted to the department of surgery because of haemorrhage ex ano and convulsive left abdominal pain. Image creative examinations revealed ileus of a probable invagination origin.

[Bilateral cancer of the male breast--a case report].

Authors give account of a rare diagnosis in connection with their male patient treated with breast cancer. They review about their case, than look over the risk factors and treatment of male breast cancer. Authors underline the importance of examinations, and the possibility of the rare diagnoses.

[Surgical treatment of malignant small bowel neoplasms--report on four cases].

About 0.3% of all malignancies and 2% of gastrointestinal tumours are malignant small bowel tumours. Many of these tumours are diagnosed during emergency surgery because of severe bleeding or acute intestinal obstruction.

[Role of the monocye-lymphocye system and of endogenous mediators in the severity of acute pancreatitis and in development of its septic complications].

The activity of monocyte/lymphocyte system and the splanchnic circulation was investigated in acute pancreatitis. The splanchnic blood flow was characterised indirectly by gastric intramucosal pH changes, which strongly correlated with APACHE-II score, and predicted the bad prognosis. The high CD14/HLA-DR and CD14/CD16 coexpression, the low TNF-alpha production proved to be unfavourable prognostic factor in the early phase of the disease.

[Calculated gastric intramucosal pH changes in the early phase of acute pancreatitis].

Based on the literature dysfunction of splanchnic circulation may be assumeol in the development of severe acute pancreatitis. Abnormal gut functions investigated by routinely used clinical examination is not available. Gastric tonometry indirectly gives information about gut function.

[Computer tomography and interventional radiologic methods in the diagnosis of acute pancreatitis].

The authors supervised the case record of 51 patients admitted between 1994 January and 1996 March suffering from acute pancreatitis. Diagnosis was made upon clinical signs, laboratory findings, abdominal ultrasound and CT examinations. In total 121 CT examinations were made mostly by using contrast material.

Effect of endotoxin administration on the severity of acute pancreatitis in two experimental models.

Conclusions: Endotoxemia can transform acute pancreatitis (AP) into a more severe form of the disease in models of AP provoked by common pancreatico-biliary duct ligation or L-arginine injection.

Background: It has been shown that systemic endotoxemia is a common feature in severe AP. The effect of endotoxemia on the course of experimental pancreatitis is unknown.

Treatment of ingrowing toenail with segmental chemical ablation.

During a 5 year period (1992-1996) 716 segmental chemical ablations using phenol solution of 80 v/v % were carried out because of ingrowing toenail. As a control, Emmert procedure was done in 200 cases. In the present study we discuss the etiology, the surgical technique of the chemical ablation and the results of the intervention.