Effect of low-glycemic-sugar-sweetened beverages on glucose metabolism and macronutrient oxidation in healthy men.

BACKGROUND/OBJECTIVES: Sugar-sweetened-beverages (SSB) provide high amounts of rapidly absorbable sugar and have been shown to impair insulin sensitivity and promote weight gain. We hypothesized that when compared with high-glycemic index (GI) SSB low-GI SSB lead to lower insulin secretion and thus an improved preservation of insulin sensitivity and fat oxidation during an inactive phase. SUBJECTS/METHODS: In a controlled cross-over dietary intervention 13 healthy men (age: 23.7±2.2 years, body mass index: 23.6±1.9 kg m(-)(2)) consumed low-GI (isomaltulose) or high-GI (75% maltodextrin+25% sucrose, adapted for sweetness) SSBs providing 20% of energy requirement for 7 days. During this phase, participant's habitual high physical activity (11 375±3124 steps per day) was reduced (2363±900 steps per day). The provided ad libitum diet comprised 55% CHO, 30% fat and 15% protein. Glycemic and insulinemic responses were assessed: Day-long (7-day continuous interstitial glucose monitoring, 24-h-urinary c-peptide excretion), during meal test (37 g isomaltulose vs 28 g maltodextrin+9g sucrose) and measures of insulin sensitivity (basal: homeostasis model assessment of insulin resistance (HOMA-IR), postprandial: Matsuda-ISI). Macronutrient oxidation was assessed by non-protein respiratory quotient (npRQ) in the fasted state (npRQfasting) and postprandial as the area under the npRQ-curve during meal test (npRQtAUC-meal). RESULTS: Day-long glycemia was lower with low-GI compared with high-GI SSB (-5%, P<0.05). Low-GI SSB led to lower insulin secretion during meal test (-28%, P<0.01) and throughout the day (-31%, P<0.01), whereas postprandial glucose levels did not differ between low-GI and high-GI SSBs. Insulin sensitivity deteriorated on inactivity with both SSBs, but was better preserved with low-GI isomaltulose compared with high-GI maltodextrin-sucrose (ΔHOMA-IR: +0.37±0.52 vs +0.85±0.86; ΔMatsuda-ISI: -5.1±5.5 vs -9.6±5.1, both P<0.05). Both, fasting and postprandial fat oxidation declined on inactivity, with no difference between high-GI and low-GI SSBs. CONCLUSIONS: Compared with high-GI SSB, 7-day consumption of beverages sweetened with low-GI isomaltulose had beneficial effects on inactivity-induced impairment of glucose metabolism without effecting fuel selection.

The prognostic significance of human epidermal growth factor receptor correlations in squamous cell cervical carcinoma.

UNLABELLED: The aim of this study was to investigate the expression and prognostic influence of HER1 (EGFR), HER2 (c-erb-B2), HER3 (c-erb-B3) and HER4 (cerb-B4) in squamous cell cervical carcinomas (SCC) and the importance of receptor correlations. PATIENTS AND METHODS: 78 SCC were stained immunohistochemically for HER1-HER4. HER2 gene amplification was determined using fluorescence in situ hybridization (FISH). Parametric correlations were performed between the four receptors and tumor characteristics. Overall survival was evaluated by uni- and multivariate analyses. RESULTS: Overexpression was found in 63% of SCC for HER1, in 21.8% for HER2, in 74.4% for HER3 and in 79.5% for HER4. Correlations were observed between HER1 and HER4 (p = 0.019). Survival analyses revealed a significant association of HER1 overexpression with favorable outcome (p = 0.016), while overexpression of HER2 and HER3 was associated with poor prognosis (p = 0.006; p = 0.05, respectively). HER1 remained significant in multivariate analysis. CONCLUSION: These data suggest that the prognostic relevance of the different HER receptors is influenced by the balance between the various receptors, especially of HER4.

Significant changes in circulating plasma levels of IGF1 and IGFBP3 after conventional or dose-intensified adjuvant treatment of breast cancer patients with one to three positive lymph nodes.

The insulin-like growth factor 1 (IGF1) and its binding protein IGFBP3 (insulin-like growth factor binding protein 3) play a pivotal role during the growth and development of tissues. The purpose of this study was to evaluate the influence of anthracycline- and taxane-containing adjuvant chemotherapy in breast cancer patients on the circulating plasma levels of IGF1 and its main binding protein, IGFBP3. This investigation was part of a prospective randomized phase III study in which breast cancer patients were treated with either conventional or dose-intensified adjuvant chemotherapy. The factors were quantified in the plasma of 151 patients with a commercially available sandwich enzyme immunoassay. Before therapy, both parameters were within the normal range in most patients (n=145 and n=144). After therapy, both factors had increased significantly by 29% (IGF1) and 19% (IGFBP3), with the highest increase being observed in the dose-intensified group. Correlations with patient and tumor characteristics revealed a relatively higher increase in both parameters in premenopausal patients, patients with lower-grade tumors, more positive lymph nodes, larger tumor volume, and positive hormone receptor status. No correlation was found with the HER2 expression of the tumors.

Inhibition of rat renal 11 beta-hydroxysteroid dehydrogenase by steroidal compounds and triterpenoids; structure/function relationship.

Various compounds with steroidal structure were tested for inhibitory effects on enzymatic activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) from rat renal microsomes. Most substances exerting inhibitory potency on both the oxidative as well as the reductive activity can be classified into two main groups: pentacyclic triterpenoids of the oleane type and steroidal detergents of the CHAPS-series. Inhibition is competitive, as was shown for one compound of each group. The IC50 values of the various inhibitors range over five orders of magnitude. In all cases, oxidative activity was inhibited more effectively than reductive activity. An attempt has been made to correlate structural properties and inhibitory potency. In brief, inhibition seems to be enhanced by a C11-oxygen function, which is present in all endogenous glucocorticosteroids and a C7-OH function. Inhibition is reduced by a large and polar substituent at C3 in the A-ring. A large D-ring substituent, such as a bisgluconamidopropyl side chain or even an additional E-ring, does not prevent binding to the enzyme, although inhibition seems to be influenced by its steric conformation. The cardiac glycosides and steroidal antibiotics tested exert no inhibitory effect on 11 beta-HSD. Cholesterol and pentacyclic triterpenoids of the lupane type exhibit a very poor inhibition, probably caused by the localization of planar structures in the ring systems, which differs from that of the effective oleane type inhibitors.

Gestational age dependence of 11 beta-hydroxysteroid dehydrogenase and its relationship to the enzymes of phosphatidylcholine synthesis in lung and liver of fetal rat.

Increase in fetal surfactant synthesis and lung maturity is caused by the glucocorticoidal induction of enzymes required for phosphatidylcholine (PC) synthesis towards the end of gestation. The regulation of gestational age-dependent induction of PC synthesis by glucocorticoids is still unclear. Since 11-beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity and its metabolising capacity for glucocorticoids have been suggested to play a central role in this regulation, we measured the gestational age-dependent changes in 11 beta-HSD and PC synthesizing enzymes in lung and liver of fetal rat. The activity of cholinephosphate cytidyltransferase (CCT; key enzyme in PC synthesis), choline phosphotransferase (CPT) and lysolecithin acyltransferase (LAT) were found to increase gradually in the lung towards the end of gestation, reached peak values at term followed by a decrease of activity reaching finally adult levels. Only CK activity exhibited constant levels until term followed by a slight increase after the birth. In comparison with the lung, the liver enzymes followed a similar pattern, but at a higher rate of activity except for CCT which was higher in the lung. The activity of 11 beta-HSD in fetal lung microsomes was detectable from day 20 and increased towards the end of gestation in the lung and liver of the rat. Oxidase activity was always found to exceed the reductase activity. The activity of 11 beta-HSD continued to increase after delivery and reached peak levels in adult animals in both organs. In order to test the hypothesis, whether 11 beta-HSD activity and PC synthesis are induced by increasing endogenous glucocorticoidal levels, we examined on day 19 of gestation the effect of dexamethasone (DEXA) on enzymatic activities (11 beta-HSD, CCT) and on [14C]choline incorporation in phosphatidylcholine in fetal lung organoid cultures. Additionally, changes in CCT activity in fetal lungs after maternal administration of DEXA were measured. DEXA accelerated 11 beta-HSD and CCT activities as well as [14C]choline incorporation. We conclude, that endogenous glucocorticoids induce PC synthesis as well as 11 beta-HSD activity in lung and liver of the fetal rat. Fetal PC synthesis is not altered by increasing 11 beta-HSD levels, because the increase of free serum corticosterone levels apparently exceeds the metabolising capacity of 11 beta-HSD towards term.

Correlation of surfactant phosphatidylcholine synthesis and 11 beta-hydroxysteroid dehydrogenase in the fetal lung.

Glucocorticosteroids (GCS) are prerequisite for the induction of surfactant synthesis in the fetal lung. The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) regulates the intracellular concentration of biologically active GCS. In this study we demonstrate the correlation of 11 beta-HSD activity and the GCS-induced surfactant phosphatidylcholine synthesis in organoid cultures of fetal rat lung. In the first series of experiments, [3H]corticosterone (CORT) or [3H]11-dehydrocorticosterone (11-DHC) were added to lung organoid cultures to test 11 beta-HSD activity. We found a low oxidative and a high reductive conversion indicating that in intact cells the equilibrium tends to biologically active GCS. However, in homogenized organoid cultures oxidative outweighed reductive activity. Secondly, the phosphatidylcholine synthesis of organoid cultures was enhanced by preincubation with GCS. CORT, as well as the hormonally inactive 11-DHC, increased the incorporation of [14C]choline into phosphatidylcholine. The effect of the latter was completely inhibited by glycyrrhetinic acid (inhibitor of 11 beta-HSD) indicating that it is caused by a previous conversion of 11-DHC into CORT via 11 beta-HSD. Thirdly, preincubation with GCS also altered 11 beta-HSD activity: dexamethasone or CORT both decreased the oxidative and increased the reductive activity in intact cells, indicating that glucocorticoids increase the rate of their own activation by positive feedback.

Inhibition of 11 beta-hydroxysteroid dehydrogenase activity enhances the antiproliferative effect of glucocorticosteroids on MCF-7 and ZR-75-1 breast cancer cells.

This in vitro study on MCF-7 and ZR-75-1 breast cancer cells showed that the antiproliferative action of glucocorticosteroids (GCS) on breast cancer cells is weakened by a high oxidative activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD; EC 1.1.1.146): both endogenic as well as synthetic GCS (dexamethasone, prednisolone) were metabolised to hormonally inactive 11-dehydro metabolites. This enzymatic shield protected the breast cancer cells from the antiproliferative action of GCS. Continuous exposure of breast cancer cells to GCS resulted in enhanced 11 beta-HSD activity. The intracellular GCS concentration was further reduced by this feedback and thus the antiproliferative effect was additionally weakened. These mechanisms of GCS deactivation could be influenced by inhibiting 11 beta-HSD with the liquorice compound glycyrrhetinic acid (GLY). In MCF-7 and ZR-75-1 cultures the antiproliferative effect of GCS was significantly increased by GLY.

Comparison of "Gen-Probe" DNA probe and PCR for detection of Listeria monocytogenes in naturally contaminated soft cheese and semi-soft cheese.

A comparison was made of three approaches for the detection of Listeria monocytogenes in naturally contaminated soft cheese and semi-soft cheese after enrichment. Enrichment broths were tested by plating them onto different selective agars, by "Gen Probe" DNA hybridization and by the polymerase chain reaction (PCR). Based on two-step enrichment, all three approaches showed high specificities (90% or more) in detecting L. monocytogenes. In contrast, the sensitivity of the Gen-Probe test was low (33% or less), whereas high sensitivities were obtained with selective plating and PCR (83% or more). Based on one-step enrichment, specificities again were high for selective plating and PCR assay (100%), whereas for the Gen-Probe assay the specificity was lower (88% or more). The best sensitivities were observed with selective plating (67%) and PCR (75%). In terms of sensitivity, specificity and analysis time, PCR applied to a two-step enrichment was the most powerful assay for detecting L. monocytogenes in soft and semi-soft cheese.

Therapy of metastatic breast cancer with humanized antibodies against the HER2 receptor protein.

The HER2 protein, a member of the epidermal growth factor family, is encoded by the protooncogene c-erbB-2. Its overexpression, occurring in approximately one-third of all breast carcinomas, is associated with a poor prognosis. A humanized mouse antibody against HER2 has been developed by genetic engineering. Here an unspecific human IgG was connected to the recognizing mouse IgG fragment. The allergization typical for allogeneic antibodies does not take place in this context. The effectiveness of this antibody has been confirmed by two international prospective phase III trials that tested it alone and combined with chemotherapy. Both modes of application increased the response rates and the time to progression. Side-effects were rare except for a high rate of cardiac dysfunction when the antibody was combined with anthracyclines. The effectiveness and negligible side-effects of the chimeric antibody against HER2 (Herceptin) render it a valuable tool in the treatment of breast cancer.

Chronic viral hepatitis B and C: an argument against the conventional classification of chronic hepatitis.

The classification of chronic hepatitis distinguishing benign chronic persistent hepatitis from severe chronic active hepatitis was constructed without knowledge of well-defined aetiological factors. Better understanding of the different hepatitis-viruses has shed new light on this subject. Chronic viral hepatitis B and C each show typical histological patterns. The validity of the conventional classification has been evaluated by a comparative study of chronic viral hepatitis B and C. 130 biopsies from 110 patients with chronic hepatitis C (CH-C) proven serologically by antibodies (second generation testing) were compared with 105 biopsies from 73 patients with chronic hepatitis B (CH-B). These were scored semi-quantatively. In CH-C, lymphoid follicles and/or aggregates were found in 88.5%, fatty degeneration in 51%, bile duct lesions in 46.2%, and Mallory body-like material in the hepatocytes in 9.2%. The portal lymphocytic infiltration generally predominated over the necro-inflammatory lesions of the parenchyma. Chronic persistent hepatitis (defined by the presence of portal hepatitis) was present exclusively in CH-C. Chronic lobular hepatitis was found exclusively in CH-B. We conclude that the histological criteria described for CH-C are highly suggestive of the diagnosis, that the artificial subdivision of chronic hepatitis into CPH and CAH is obsolete and that the histological assessment of chronic hepatitis should consist of a grading of inflammatory activity (minimal, mild, moderate, severe) and staging of fibrosis (extent of distortion of architecture). The final diagnosis should be based on the demonstration of the aetiological agent.

Endogenous inhibitors of 11 beta-OHSD: existence and possible significance.

Inhibition of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) by licorice-derived compounds and in cases of idiopathic impairment of this enzyme is known to result in hypermineralocorticoid syndromes, reflecting corticosteroid receptor activation by excess intracellular glucocorticoids. In this paper we address the question of whether or not endogenous inhibitors of 11 beta-OHSD exist that might cause pathological glucocorticoid metabolism. Using microsomal preparations we have demonstrated that bile acids are potent inhibitors of rat renal and human hepatic 11 beta-OHSD, with lithocholic acid exerting the strongest effect. The human renal enzyme is affected to a lesser extent. Serum of patients with cholestatic liver cirrhosis also inhibited 11 beta-OHSD activity, in parallel with total bile acid concentration. Cholesterol and its precursor lanosterol inhibited the enzymatic activity in microsomes from rat and human kidney cortex and human liver. We conclude that bile acids could contribute to the abnormalities of cortisol metabolism observed in cholestatic liver cirrhosis.

Evaluation of root-resected teeth. Results after 10 years.

There are only a few long-term investigations on root-resected teeth in the literature. This article is a 10-year review of 28 root-resection cases, which mainly had been used as bridge abutments. The periodontal, prosthetic, and endodontic problems were evaluated. After 10 years a total failure rate of 32% was observed. The analysis of the failure causes revealed that endodontic--not periodontal--complications were predominating. The study also includes a comparison of root-resected teeth restored with root screws and composite cores versus those which had been restored with cast gold dowels, showing that both types of reconstruction had the same durability concerning the risk of root fractures or loss of retention.

Multiple hepatitis attacks with immunothrombocytopenia in a heroin addict.

A 25-year-old heroin-addict had four episodes of acute hepatitis, each of them associated with thrombocytopenia. Serologically, hepatitis A and B as well as cytomegalo- or Epstein-Barr virus infections were excluded. High levels of circulating immune complexes and antibodies reacting with aminophospholipids, a component of both liver cell and platelet membranes, were detected during the last two attacks of hepatitis, but were absent during remission. Platelet-associated antibodies of the IgM class paralleled the 'anti-phospholipid' antibodies during the fourth attack. These findings demonstrate an immunological basis of the thrombocytopenia and point to the possibility of a direct association between liver cell injury and peripheral platelet destruction in certain patients.

Survival rates of hemisected teeth: an attempt to compare them with survival rates of alloplastic implants.

Use of hemisection in an attempt to preserve multirooted teeth that have furcation involvement has increased in recent years. However, there are few long-term studies of the success of this treatment. Furthermore, it is difficult to compare results of different studies because of differences in the length of follow-up and the criteria for failure. Results of various studies were reduced to a common denominator to allow comparison. The compiled results of studies on hemisection revealed an average reported failure rate of 13.1%. This rate was compared with results of studies on implants; the failure rates of the two treatment alternatives are not substantially different. Thus, because hemisection is a relatively simple, inexpensive treatment with a good chance of success (given appropriate case selection), it should always be considered as an option before molar extraction.

Intra-alveolar transplantation of deeply fractured roots after elongation with titanium roots screws.

Teeth with deep transverse or oblique fractures have posed severe challenges for treatment in the past. Today, such teeth can be saved by transplantation within the alveolus. In this pilot study, a technique is described by means of which roots otherwise determined to be too short can be salvaged. Fourteen fractured short roots were extracted carefully, elongated with titanium screws, and subsequently replanted.

[Colonic polyps: clinical and practical implications]. / Kolonpolypen: klinische und praktische Implikationen.

Among colorectal polyps, various forms of neoplastic or non-neoplastic lesions are distinguished by histology. Most accumulated knowledge suggests that the majority of cancer of the colon arise in pre-existing benign neoplastic polyps (adenoma-carcinoma sequence). Because of the risk of cancer being already present, all adenomatous polyps must be removed in toto. The carcinoma may occupy only a small area of the polyp, and therefore, forceps biopsies are inappropriate due to the sampling error. Since patients with polyps detected by rectosigmoidoscopy often have further polyps in the remaining part of the colon, complete examination of the whole colon is required. Follow-up examinations are indicated, because the risk of developing new polyps is high. Studies of the life history of the adenoma-carcinoma sequence suggest that interval of complete large-bowel follow-up may be about 5 years. The policy of polypectomy and follow-up examinations should be possible to prevent the development of colorectal cancer.

[Endoscopic treatment of bile duct stones and their complications]. / Endoskopische Behandlung von Gallengangssteinen und deren Komplikationen.

Endoscopic treatment of bile duct stones has reached a high degree of perfection by the introduction of adjuvant therapies raising the rate of success while at the same time reducing risk. Large stones are fragmented mechanically or by means of extracorporal shock wave lithotripsy thus permitting to avoid a long and risky papillotomy. Drainage of the bile is assured with a nasobiliary drain in case of primary failure reducing the risk for cholangitis. Endoscopic treatment is the choice for residual or recurring stones after cholecystectomy and for severe purulent cholangitis in which surgical treatment is still charged with a high mortality. Endoscopic stone removal is further indicated when an operation per se carries a high risk. Long-term studies have demonstrated that even patients in which the gall bladder is preserved stay free of recurrence. In patients with severe biliary pancreatitis early papillotomy reduces complication-rate and mortality. The question remains unsettled whether patients at normal risk with simultaneous cholecysto- and choledocholithiasis should undergo direct cholecystectomy and bile duct revision or if they could profit from endoscopic removal of stones prior to cholecystectomy.

[Ultrasonically-guided sclerosing of kidney and liver cysts using polidocanol]. / Ultraschallgeführte Sklerosierung von Nieren- und Leberzysten mit Polidocanol.

First experiences are reported with percutaneous sclerosing therapy of cysts with polidocanol (aethoxysklerol 1%) using ultrasound for needle guidance. They cover two patients with symptomatic cysts of the liver and a patient with polyglobulinemia and an erythropoietin-producing renal cyst. These experiences are compared to previously reported ones.