Surface modification of poly(methyl-methacrylate) with farnesol to prevent Candida biofilm formation.

Candida albicans promotes biofilm formation on dentures, which compromises the use of poly(methyl-methacrylate) (PMMA) as a dental material. Farnesol (FAR), a natural compound that prevents C. albicans filamentation and biofilm formation, was incorporated into the PMMA matrix, to obtain antifungal PMMA_FAR materials. The tested concentrations (0·0125% and 0·4%) of FAR, 24 h after incubation on YPD agar, inhibited filamentation of C. albicans. PMMA was modified with different FAR concentrations (3-12%), and physicochemical properties, antifungal activity and cytotoxicity of these modified materials (PMMA_FAR) were tested. The presence of FAR in PMMA_FAR composites was verified by Fourier-transform infrared spectroscopy (FT-IR). Incorporation of FAR into the polymeric matrix significantly decreased hydrophilicity at all tested concentrations and significantly reduced biofilm and planktonic cells metabolic activity in the early stage of biofilm formation at ≥6% FAR in PMMA. PMMA_FAR composites with <9% FAR were non-toxic. Modification of PMMA with FAR is a good strategy for reducing C. albicans biofilm formation on dentures.

Recurrent Dystonic Crisis and Rhabdomyolysis Treated with Dantrolene in Two Patients with Aromatic L-Amino Acid Decarboxylase Deficiency.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare, autosomal recessive inborn error of metabolism in which several neurotransmitters including serotonin, dopamine, norepinephrine and epinephrine are deficient. Symptoms typically appear in the first year of life and include oculogyric crises and dystonia, hypotonia, and global developmental delay. Dystonia is of particular concern as a dystonic storm can ensue leading to rhabdomyolysis. Rhabdomyolysis can become life-threating and therefore its recognition and prompt management is of significant importance. Here we present two cases of patients with AADC deficiency and a history of dystonic crisis causing rhabdomyolysis. We hypothesize that in addition to the hypodopaminergic, a hypercholinergic state is contributing to the pathophysiology of dystonia in AADC deficiency, as well as to the associated rhabdomyolysis. We were able to prevent rhabdomyolysis in both patients with using Dantrolene and we suggest using a trial of this medication in cases of sustained dystonic crisis in AADC deficiency patients.

Survivin expression in patients with newly diagnosed nodal diffuse large B cell lymphoma (DLBCL).

Survivin is one of the inhibitors of apoptosis proteins (IAP) that might play an important role in the pathogenesis of diffuse large B cell lymphoma (DLBCL). The present study was designed to investigate the clinical and prognostic significance of survivin expression in nodal DLBCL. We analyzed lymph node biopsy specimens obtained from 56 patients with newly diagnosed nodal DLBCL, treated with immunochemotherapy (R-CHOP). The expression of survivin was analyzed using the standard immunohistochemical method on formalin-fixed and routinely processed paraffin-embedded lymph node specimens and evaluated semiquantitatively as a percentage of tumor cells. Survivin immunoexpression (>45 % positive tumor cells) was found in 22 (39.28 %) and observed as cytoplasmic staining in 15 patients, or mixed (cytoplasmic and nuclear) staining in 7 patients. A significant difference in survivin immunoexpression was noticed between the GCB and the non-GCB subtypes of DLBCL (p = 0.031). However, survivin immunoexpression had no significant association with IPI, "bulky" disease, extranodal localization, hemoglobin, Ki-67 immunoexpression or other clinicopathological parameters. A univariate analysis showed that survivin positivity was an unfavorable factor for therapy response and a predictor of shorter survival in patients with DLBCL (p = 0.048 and p = 0.034, respectively). Patients with survivin overexpression experienced a relapse more often than patients without expression of this apoptotic protein (27.3 vs. 11.8 %), but this difference did not reach statistical significance (p = 0.131). The results of this study showed that disregulation of survivin expression had an important role in the determination of the course of the disease in patients with nodal DLBCL treated with R-CHOP. Therefore, survivin represents a potential target for therapeutic intervention in DLBCL.

The use of parenteral nutrition for the management of PKU patient undergoing chemotherapy for lymphoma: a case report.

The metabolic control of phenylalanine levels is a challenge during illness. We present the metabolic management of a 6 year old boy with classical PKU who was diagnosed with stage III intraabdominal Burkit's lymphoma and underwent surgical resection and chemotherapy. The metabolic control during chemotherapy was achieved by the use of parenteral custom made amino acid solution and pro-active adjustment of intake. From the 94 obtained plasma phenylalanine (Phe) levels, 18.4% were above our clinic's recommended upper limit (360 µmol/L, 6 mg/dL) while 52.7% of Phe levels were below the recommended lower limit (120 µmol/L, 2 mg/dL). Phe levels above recommended range were associated with low caloric/protein intake, while levels below recommended range reflected the difficulty in achieving the full prescribed Phe intake. We recommend early institution of custom made amino acid solution with maximum amino acid content and caloric intake to provide optimal phenylalanine control. Administration of phenylalanine via regular intravenous amino acid solution may assist in avoiding low Phe levels when prescribed intake is compromised due to vomiting and other disease related illnesses. Use of custom made, phenylalanine free amino acid solution proved beneficial in the management of blood phenylalanine levels in a PKU patient during chemotherapy for Burkitt lymphoma.

Biological and clinical features of non-Hodgkin's lymphoma in the elderly.

PURPOSE: The incidence of non-Hodgkin's lymphomas (NHLs) in elderly people has increased in recent years because the world population is getting older. The aim of this study was to compare the biological and clinical features in patients diagnosed with NHLs younger and older than 65 years, and the possible influence of age on the choice of optimal therapeutic approach. METHODS: We retrospectively evaluated 193 patients with NHLs: 111 (68%) were <65 years and 82 (42%) ≥65 years. The following parameters were analysed: age, gender, clinical stage, International Prognostic Index (IPI), histological type, presence of B symptoms, disease localization, presence of bulky mass, Karnofsky performance status (PS), comorbidities, blood counts, liver and renal function and serum LDH. RESULTS: Elderly patients had statistically more frequent indolent NHLs (p=0.036), IPI 3 and 4 (p<0.0001), presence of comorbidities (p<0.001), and less frequent presence of bulky disease (p7equals;0.043). Response to therapy was different in the 2 age groups: 29% of patients ≥65 years achieved complete remission (CR) in contrast to 71% of patients <65 years (p<0.001). The most frequent cause of death was disease progression (PD) (86% of younger patients and 71% of elderly patients (p7equals;0.150). Older patients died more frequently because of comorbidities compared younger ones (21 and 107percnt;, respectively; p=0.250), and had more complications of therapy (8.1 and 47percnt;, respectively (p=0.320). Overall survival (OS) was shorter in older patients in all lymphoma types: indolent lymphoma (36 vs. 17 months), aggressive (22 vs. 20 months) and very aggressive (14 vs. 1 months). Multivariate analysis showed that parameters for shorter survival in the elderly were Karnofsky PS <60, increased serum LDH and treatment toxicity. CONCLUSION: In elderly NHLs patients, treatment response and survival are significantly poorer. Since older patients mostly died of PD, they should be treated with standard regimens and best supportive measures.

What are additives?

Historical development of the concern exercised by the public institutions of a country for the food taken by their citizens, through care for its safety and proper testing by authorized governmental institutions, is presented. In the USA, FDA was established for this purpose, whereas European Union agencies are in charge in Europe. Additives are listed and classified according to E-number groups introduced in the European Union in 1990. Difference between the additives and supplements is explained. Special reference is given to an anonymous leaflet that appeared in Zagreb in the autumn 2000, in which some additives were described as harmful, detrimental, carcinogenic and highly hazardous, providing no valid arguments for such a statement. The author considers it merely an unargumented propaganda attack on particular European food manufactures.

Coffee and health in the elderly.

Coffee is a very attractive but not a unique drink. There are various types of coffee, e.g. Arabica, Canephora, and Robusta. In addition, various coffee blends containing several coffee types of different origin are offered in coffee-houses in Croatia and worldwide. These coffee blends can differ substantially according to their components, especially to the proportion of caffeine. Caffeine is the major coffee constituent which the coffee tolerance or intolerance depends on. In a healthy liver, the majority of caffeine is degraded by the hepatic microsomal enzymatic system. Caffeine is mostly degraded to paraxanthine substances, partially to theobromine and theophylline, and a small amount of unchanged caffeine is excreted by urine. Therefore, the metabolism of caffeine depends on the state of this enzymatic system of the liver. Elderly individuals with a depleted enzymatic system do not tolerate coffee with caffeine. They are recommended to take decaffeinated coffee, and this only if their stomach is healthy, because both decaffeinated coffee and coffee with caffeine cause heartburn. Moderate amounts of coffee (50-100 mg of caffeine or 5-10 g of coffee powder a day) are well tolerated by a majority of elderly people, who enjoy to meet and chat over a cup of coffee. Excessive amounts of coffee, however, can in many individuals cause very unpleasant, exceptionally even life-threatening side effects. Therefore, elderly persons are recommended to take moderate amounts of coffee which will not cause any health impairments.

Nutrition and dietetics--neglected subjects in medical education.

A brief historical review of the development of nutrition and dietetics in the world is followed by concise description of the history of the discipline in Croatia after the foundation of the School of Medicine in Zagreb in 1919. As differentiated from the Schools of Medicine in Zagreb, Rijeka, Osijek and Split, the third, nutritional curriculum at the School of Food Science and Biotechnology has allocated as many as 280 theoretical and 110 practical periods in the form of seminars (15 periods) and practical exercise (95 periods) to nutrition and dietetics. The curriculum includes special course of lectures in dietetics, delivered by a physician specialized in the field. This is followed by the observation that none of the four Croatian Schools of Medicine in Zagreb, Rijeka, Osijek and Split has introduced systematic education in the field in either undergraduate or postgraduate curricula. There are only some sporadic related topics included in undergraduate and postgraduate studies. Thus, the paper points to the serious neglect of this important subject in the curricula of our medical schools, and present some ideas how to solve the problem in the nearest future. The possible organization of a special postgraduate study in nutrition and dietetics for physicians willing to devote themselves professionally to this field of medicine is strongly advocated, because modern nutritional practices and dietetics are likely to soon impose the need of such experts in every large hospital and clinical department.

Probiotics or microbes against microbes.

The brief historical survey of the discovery of Lactic Acid Bacteria (LAB) is followed by an account of the studies of LAB, since 1965 by many researchers named probiotics or biotherapeutic agents. However, as their action also involves certain antibiotic characteristics, the term "biotherapeutic bacteria" appears to suit them best. The favorable clinical effect of many LAB on various pathologic states in humans, especially in children, has now been positively demonstrated. Clinical success achieved by particular LAB in different pathologic conditions is described, with special reference to the scientifically verified effects of LGG, which has also been used in Croatia for the manufacture of fermented dairy products since 1998.

Ultrasound diagnosis of acute viral hepatitis.

In acute viral hepatitis, ultrasound examination of the liver also reveals pathologic changes of other organs, especially of the gallbladder and, less frequently, of the pancreas and regional lymph hilar nodes. Ninety patients divided into 3 groups of 30 patients each, suffering from viral hepatitis (group 1), acute calculous cholecystitis (group 2) or liver cirrhosis (group 3), were prospectively analyzed. An increased gallbladder wall thickness of 4.67 +/- 0.66 mm was recorded in all group 1 patients. In the group with acute viral hepatitis, gallbladder wall thickening was only present during the first week of the disease, and was almost two-fold thinner than that found in the group with acute calculous cholecystitis, where it ranged from 4.3 to 10.3 mm. The gallbladder wall thickening in cirrhosis patients was found to depend on liver decompensation during the course of cirrhosis.

Dietary fiber and retrograde starch.

The history of the recognition of the importance of dietary fiber, their current classification into water-soluble and water-insoluble fiber, and lignin, a single non-carbohydrate fiber, and the physiologic role of dietary fiber, with particular reference to retrograde starch resistance to small intestine digestion, are briefly presented. Dietary fiber are highly hygroscopic, thus they greatly contribute to stool voluminosity by binding water, decrease the glycemic index, and exert a protective action, via an as yet unknown mechanism, against the occurrence of colon cancer. It should be added that some dietary fiber decrease the concentration of cholesterol in the blood, i.e. in the human body. The importance of the methodology used for NSP determination is underlined, since some methods determine only some of the polysaccharides, other also measure some other substances, whereas Englyst's method determines NSP only.

Historical development of Croatian radiology.

The history of the development of Croatian radiology is described, from the first beginnings to the present. Very soon after Roentgen's discovery in 1895, not only communications and informative lectures, but also the first x-ray device appeared in Zagreb and then in many other towns in Croatia. The first specialists in roentgenology and x-ray technician were educated at Professor Holzknecht's Roentgenology Institute in Vienna. After the opening of the University School of Medicine in Zagreb in 1917/1918, the Chair of Roentgenology, headed by Professor L. Popovic, was founded as early as 1922. Here the first specialization for physicians was organized. After the second world war, with the foundation of Medical Schools in Rijeka, Osijek and Split, Croatian radiology steadily progressed. Autonomous departments and institutes for diagnostic and therapeutic radiology were organized at all large medical centers. Thanks to gynecologists, ultrasound has not only developed at radiologic units, but also at departments of gastroenterology, orthopedics, pediatrics and others. Today, there are many units for interventional ultrasonography throughout Croatia. Radioisotope units have also been organized, but only in the main medical centers, rarely in small ones. At present, there are five radiotherapy and oncology institutions in Zagreb, and one in Rijeka, Split and Osijek. Interventional radiology has been well organized since the 80s, and the First Congress of Diagnostic and interventional Radiology was held in Rijeka in 1994. In conclusion, there is no doubt that the Croatian radiology keeps pace with the international advances in the field.

Energy metabolism of reticulocytes: two different sources of energy for Na+K(+)-ATPase activity.

Total energy production in rabbit reticulocytes amounted to 136.52 +/- 6.50 mumol ATP h-1 ml-1 of reticulocytes: 88.3 per cent was provided by oxidative phosphorylation, whereas only 11.7 per cent by aerobic glycolysis. Na+K(+)-ATPase accounted for 23 per cent, i.e. 27.65 +/- 2.55 mumol ATP h-1ml-1 of reticulocytes, in the overall energy consumption in reticulocytes of rabbits. Under basal conditions ATP for Na+K(+)-ATPase activity was derived exclusively from oxidative phosphorylation. However, when the activity of Na+K(+)-ATPase was increased due to the stimulation of adenylate cyclase by (-)-isoprenaline, the additional energy required was provided by aerobic glycolysis. These results indicate that two different compartments, one cytosolic and the other mitochondrial, provide energy for Na+K(+)-ATPase activity in reticulocytes.

Cadmium-induced changes of antioxidant and metabolic status in red blood cells of rats: in vivo effects.

Chronic exposure of adult rats to dietary intake of cadmium (15 mg CdCl2/day/kg for 30 days) leads to development of anemia and thrombocytosis. Anemia is characterized by significant reticulocytosis (13.1 +/- 1.0%), anysocytosis, poikilocytosis, iron deficiency and marked alterations of antioxidant and metabolic status of red blood cells. Activities of SOD, catalase, GPx and GR were significantly increased in red blood cells of cadmium-treated rats. In treated animals cadmium induced an increase of red cell reduced and oxidized glutathione with no changes of GSSG/GSH ratio. However, significant reduction of lipid peroxidation was found. Plasma levels of tocopherol and ascorbate, as well as activity of glutathione-S-transferase, were all significantly increased in cadmium-treated rats. The energy metabolism of red blood cells was deeply altered in cadmium-treated rats. The levels of ATP, ADP, AMP and TAN were significantly increased while ATP/ADP ratio and adenylate energy charge (AEC) were significantly reduced. The level of 2,3-BPG was somewhat lower, but 2,3-BPG/Hb ratio was considerably higher, in red blood cells of cadmium-treated rats.

Maturation-dependent changes of the rat reticulocyte energy metabolism and hormonal responsiveness.

Significant reduction of total and coupled respiration as well as an increase of uncoupled respiration characterize the maturation of rat reticulocytes. ATP declines by 45%, whereas ADP increases by 70% and the ATP/ADP ratio decreases from 7.6 to 3.3. At the same time the oxygen-delivery capacity of red blood cells increases by 37% due to an increase of 2.3-BPG level. In the youngest reticulocytes the basic level of cAMP is 2-fold higher, whereas the maximal (-)-isoproterenol-induced accumulation of cAMP is 8-fold higher than in the fraction of most mature reticulocytes. Evidence for the presence of functionally active glucagon-receptors in reticulocytes is presented, with maturational inactivation/disappearance of R2-glucagon receptors.

Effects of phenylhydrazine hydrochloride on energy metabolism in rabbit erythrocytes and reticulocytes.

The effects of 1, 5 and 20 mmol/l phenylhydrazine hydrochloride on energy metabolism of rabbit erythrocyte and reticulocyte were studied. Significant depression of glycolysis, accompanied by loss of adenine nucleotides, mainly due to an extensive decline of ATP, was found in erythrocytes. Energy metabolism of reticulocytes appears to be more sensitive to deleterious effects of this drug. The declines of ATP and sum of all adenine nucleotides, as well as the accumulation of hypoxanthine were twofold in reticulocyte-rich red cell suspensions compared with suspensions of mature erythrocytes. It can be concluded that these changes are the consequence of lower energy production due to phenylhydrazine hydrochloride-induced inhibition of oxidative phosphorylation.

[Evaluation of disorders of portal and total hepatic blood flow in patients with chronic diffuse liver diseases]. / Procjenjivanje poremecaja portalnog i ukupnog hepatalnog protoka krvi u bolesnika s kronicnom difuznom bolescu jetre.

The total hepatic blood flow measured with radioactive colloidal gold and the portal blood flow with the echo-Doppler method were investigated in 19 healthy examinees and 63 patients with chronic diffuse liver diseases. In the group of healthy examinees, the average values of the total hepatic blood flow was 1254 +/- 231 ml/min and of the portal one 1104 +/- 227 ml/min. The lowest blood flow values were obtained in patients with decompensated cirrhosis, especially in the hepatic (704 +/- 186 ml/min) and the portal blood flow (562 +/- 198 ml/min). In all the groups of examinees, registered values of the total hepatic blood flow were significantly higher than the values of the portal blood flow. The relations of the values obtained by both methods, among groups, were similar. By both methods decreased values are not obtained in liver steatosis and chronic persistent hepatitis in relation to the normal values. In patients with more serious forms of chronic diffuse liver diseases (cirrhosis and chronic active hepatitis) significantly lower blood flow values than the normal ones were obtained. Both methods contribute to the investigation of liver circulation disturbances, liver function damages, and to the follow-up of the liver disease course. The possibility of an indirect evaluation of the arterial hepatic blood flow from the difference of hepatic and portal blood flows may mean a new approach to the investigation of pathophysiological liver occurrences.

Activation and desensitization of glycolysis by stimulation of adenylate cyclase in rat reticulocytes.

Isoproterenol or forskolin induce a 10-15-fold increase in concentration of cyclic AMP in rat reticulocytes as compared with the basal level of 2.3 +/- 0.3 microM. Glycolysis is stimulated by both compounds transiently more than 2-fold with a peak after 7.5 min followed by an exponential decline. The glycolytic rate in the presence of 10 microM isoproterenol or 10 microM forskolin did not return to basal levels within 60 min of incubation, but was depressed by as much as 50% under the influence of 100 microM forskolin. This phenomenon is designated as metabolic desensitization. The stimulation of glycolysis is probably due to activation of phosphofructokinase as well as to stimulation of Na+,K+-ATPase. The diminished glycolytic flux during the period of metabolic desensitization is accompanied by a decline of glucose 6-phosphate and in the presence of high concentrations of forskolin also by a decrease in glucose 1,6-bisphosphate. A lower rate of influx of glucose is postulated.