[How useful are diets against cancer?]. / Wie sinnvoll sind "Krebsdiäten"?

BACKGROUND: Diets against cancer are attractive for patients who try to influence disease progression. METHODS: In order to determine the most influential cancer diets in Germany, we analyzed the chatroom for cancer patients "Krebs-Kompass", the search machines Google and Bing and our own counseling experience as experts. We conducted a systematic literature review of clinical data in Medline also considering preclinical data on safety. RESULTS: The most often mentioned "cancer diets" are Budwig diet, Gerson's regimen, lowcarb diet, cancer cure of Breuß and macrobiotic diet. These diets can be classified according to the principle idea of carcinogenesis as follows: cancer as a lack or abundance of a substance or as a consequence of pathological metabolism of cancer cells. Staying in line with a specific diet the patients are thought to be able to cure themselves or at least substantially contribute to cure. However, we did not find any scientific publication of a clinical study which describes positive results regarding survival. On the contrary, data show malnutrition and side effects. CONCLUSION: There is no indication to consume a "cancer diet". In some cases adverse effects can occur. Cancer patients who are discussing nutrition should be warned about taking up a "cancer diet".

Is islet autoimmunity related to insulin sensitivity or body weight in children of parents with type 1 diabetes?

AIMS/HYPOTHESIS: It has been suggested that metabolic demand and insulin resistance play a role in the development of type 1 diabetes, including the onset of autoimmunity. The aim of the present study was to determine whether insulin demand is increased in children with islet autoantibodies. METHODS: BMI standard deviation score (BMI-SDS) was measured from 2 years of age in 1,650 prospectively followed children of mothers or fathers with type 1 diabetes, including 135 who developed persistent islet autoantibodies. HOMA of insulin resistance (HOMA-IR) was determined using fasting samples from 777 of the children starting from age 5 years. RESULTS: An increased HOMA-IR was associated with female sex (p = 0.0004), older age (p < 0.0001) and increased BMI-SDS (p < 0.0001). Children with islet autoantibodies did not have an increased HOMA-IR compared with age-matched islet autoantibody-negative children (age 8 years: mean 0.61 vs mean 0.72, respectively, p = 0.21; age 11 years: mean 0.96 vs mean 1.21, respectively, p = 0.07). Furthermore, after correction for age and sex, autoantibody positivity was associated with decreased HOMA-IR values (p = 0.01). BMI-SDS was similar between islet autoantibody-positive and -negative children at age 2 (mean 0.07 vs mean 0.16, respectively), 5 (mean 0.06 vs 0.08, respectively), 8 (mean - 0.09 vs mean 0.02, respectively), and 11 years (mean 0.22 vs mean 0.16, respectively) and similar to that of national reference values. CONCLUSIONS/INTERPRETATION: Islet autoantibody-positive children in the BABYDIAB cohort are not insulin resistant and do not have an increased BMI around and early after islet autoantibody seroconversion. These findings are inconsistent with the notion that insulin resistance is a risk factor for islet autoimmunity.

Maternal type 1 diabetes reduces the risk of islet autoantibodies: relationships with birthweight and maternal HbA(1c).

AIMS/HYPOTHESIS: The risk of type 1 diabetes is reduced in the children of mothers with type 1 diabetes compared with children of fathers with type 1 diabetes. We asked whether children of mothers with type 1 diabetes also have a decreased risk of developing islet autoantibodies, and which factors associated with maternal diabetes contribute to a reduced islet autoantibody risk in offspring. METHODS: Singleton offspring of a mother (n = 1,008) or father with type 1 diabetes (n = 578) from the BABYDIAB study were included. Children were followed from birth for the development of islet autoantibodies defined as two or more autoantibodies to insulin, glutamic acid decarboxylase or insulinoma antigen 2 in two or more blood samples. RESULTS: Islet autoantibody risk was lower in children of mothers with type 1 diabetes (5 year risk, 3.2% vs 5.7% in children of fathers with type 1 diabetes; p = 0.04). Among factors that differed between pregnancies from mothers with and without type 1 diabetes, birthweight was associated with islet autoantibody risk. Risk was reduced in children with birthweights in the lower (adjusted HR 0.33; 95% CI 0.14-0.75; p = 0.009) and upper (HR 0.45; 95% CI 0.21-0.97; p = 0.04) tertiles compared with the middle tertile. A sub-analysis of maternal HbA(1c) suggested that moderately elevated third trimester maternal HbA(1c) was also associated with a reduced islet autoantibody risk in children of mothers with type 1 diabetes (5.7-7%; HR 0.38; 95% CI 0.15-0.96; p = 0.04 vs children of mothers with HbA(1c) < 5.7%). CONCLUSIONS/INTERPRETATION: The risk of islet autoimmunity is modified by maternally influenced events such as birthweight.

Breastfeeding habits in families with Type 1 diabetes.

AIMS: Breastfeeding is acknowledged to be beneficial for child development. Women with diabetes may be more likely not to breastfeed their children because of neonatal morbidity and instability in diabetes control. The aim of this study was to assess the effect of maternal Type 1 diabetes on breastfeeding habits. METHODS: Full breastfeeding and any breastfeeding were reported in the first year of life in 1560 children born in Germany between 1989 and 2004. Of those, 997 children had a mother with Type 1 diabetes, and the remaining 563 children had a father or sibling with Type 1 diabetes. RESULTS: Fewer children of mothers with Type 1 diabetes were breastfed than children of non-diabetic mothers (77 vs. 86%; P < 0.0001) and, amongst breastfed children, there was a shorter duration of full breastfeeding (12 vs. 17 weeks; P < 0.0001) and any breastfeeding (20 vs. 26 weeks, P < 0.0001) in children of mothers with Type 1 diabetes compared with children of non-diabetic mothers. Other factors associated with reduced frequency and duration of breastfeeding were pre-term delivery (P < 0.0001), young maternal age (P < 0.0001), and firstborn children (P < 0.0001). After stratification for each of these factors, breastfeeding remained significantly less frequent and of less duration in children of mothers with Type 1 diabetes as compared with children of non-diabetic mothers. CONCLUSIONS: Mothers with Type 1 diabetes breastfeed their children less than international recommendations. Counselling to increase frequency and duration of breastfeeding may be warranted in this population.

Fetal growth is increased by maternal type 1 diabetes and HLA DR4-related gene interactions.

AIMS/HYPOTHESIS: Intrauterine growth in non-diabetic pregnancies is reported to be influenced by type 1 diabetes susceptibility genes. In particular, the high-risk HLA DR4_DQB1*0302 haplotype is associated with increased birthweight. The aim of this study was to determine whether HLA DR4 was associated with increased birthweight in a maternal diabetes environment and whether effects persisted during early childhood. SUBJECTS AND METHODS: Birthweight and gestational age were obtained in singleton births from mothers with type 1 diabetes (n = 1161) or whose fathers or siblings have type 1 diabetes (n = 872). Weight and height at ages 2 and 5 years were obtained from paediatric records. Data were adjusted for (gestational) age and sex and expressed as percentiles of German reference data. HLA DR typing was obtained for all children and 1090 children also had insulin gene (INS) variable number of tandem repeats (VNTR) typing. RESULTS: Maternal type 1 diabetes was associated with increased birthweight, gestational age and birthweight percentiles (all p < 0.0001). In children of mothers with type 1 diabetes, birthweight percentile was further related to maternal HbA(1c) during pregnancy (r = 0.26; p < 0.0001) and was independently increased if children had HLA DR4 alleles (76th vs 64th percentile; p < 0.0001). HLA DR4 was not associated with birthweight in children of non-diabetic mothers. Birthweight was not associated with INS VNTR genotypes. High birthweight, but not HLA DR4 was associated with increased weight and BMI at ages 2 and 5 years (p < 0.0001). CONCLUSIONS/INTERPRETATION: Our findings are consistent with the hypothesis that a diabetic intrauterine environment interacts with gene(s) marked by the type 1 diabetes susceptibility HLA DR4 alleles to increase fetal growth.

The dependence of low-energy electron attachment to CF3Br on electron and vibrational energy.

In a joint experimental and theoretical effort, we have studied dissociative electron attachment (DEA) to the CF3Br molecule at electron energies below 2 eV. Using two variants of the laser photoelectron attachment method with a thermal gas target (T(G) = 300 K), we measured the energy dependent yield for Br- formation over the range E = 3-1200 meV with resolutions of about 3 meV (E < 200 meV) and 35 meV. At the onsets for excitation of one and two quanta for the C-Br stretching mode nu3, downward cusps are detected. With reference to the recommended thermal (300 K) attachment rate coefficient k(A)(CF3Br) = 1.4 x 10(-8) cm3 s(-1), absolute cross sections have been determined for Br- formation. In addition, we studied Br- and (CF3Br)Br- formations with a seeded supersonic target beam (10% CF3Br in helium carrier gas, with a stagnation pressure of 1-4 bars and nozzle temperatures of 300 and 600 K) and found prominent structure in the anion yields due to cluster formation. Using the microwave pulse radiolysis swarm technique, allowing for controlled variation of the electron temperature by microwave heating, we studied the dependence of the absolute DEA rate coefficient on the mean electron energy E over the range of 0.04-2 eV at gas temperatures T(G) ranging from 173 to 600 K. For comparison with the experimental results, semiempirical resonance R-matrix calculations have been carried out. The input for the theory includes the known energetic and structural parameters of the neutral molecule and its anion; the parameters of the resonant anion curves are chosen with reference to the known thermal rate coefficient for the DEA process. For the gas temperature T(G) = 300 K, good overall agreement of the theoretical DEA cross section with the experimental results is observed; moreover, rate coefficients for Br- formation due to Rydberg electron transfer, calculated with both the experimental and the theoretical DEA cross sections, are found to agree with the previously reported absolute experimental values. At T(G) = 300 K, satisfactory agreement is also found between the calculated and experimental attachment rate coefficients for mean electron energies E = 0.04-2 eV. The strong increase of the measured rate coefficients with rising gas temperature, however, could be only partially recovered by the R-matrix results. The differences may result from the influence of thermal excitations of other vibrational modes not included in the theory.

Organelle purification and selective permeabilisation of the plasma membrane: two different approaches to study vacuoles of the filamentous fungus Ashbya gossypii.

Two different approaches to prepare and characterise vacuoles from the filamentous fungus Ashbya gossypii are described, i.e. the isolation of vacuoles from hyphal cells and the controlled permeabilisation of the plasma membrane. By mechanical lysis of protoplasts and separation of the organelles on a stepped density gradient, we obtained a vacuolar fraction virtually free of contamination by other organelles, unlysed protoplasts and cell debris. The integrity of the isolated organelles was characterised by vital-staining, the presence of alpha-mannosidase, and retained accumulation of basic amino acids. In a second approach, the cell membrane of the fungus was selectively permeabilised by use of the saponin digitonin leaving the vacuoles in their physiological surrounding, i.e. protected by the rigid cell wall. The permeabilisation was monitored by the latency of predominantly cytosolic amino acids and the ATP status of the cells. Functional intactness of the vacuoles within the permeabilised hyphae was demonstrated by maintenance of the pH gradient across the vacuolar membrane as detected by accumulation of the fluorescent dye, Acridine orange. These two methods are well-suited tools for the in situ assay of intracellular compartmentation of metabolites, for vacuolar transmembrane fluxes in Ashbya gossypii, as well as for the direct access to vacuolar membranes and enzymes of this fungus.

Ultrastructure of the Corynebacterium glutamicum cell wall.

The cell wall structure of the Gram-positive Corynebacterium glutamicum was evaluated by electron microscopy of thin sections after freeze-substitution and conventional fixation with glutaraldehyde. For the cell wall an overall thickness of approximately 32 nm was determined, with 8.5 nm corresponding to an outer layer, 6.5 nm to an electron translucent region (ETR) as found in mycobacteria and 17 nm to the peptidoglycan. Knob-like surface structures previously observed in freeze-fracture experiments were detected when cells were conventionally processed with a fixation using glutaraldehyde. By mild treatment with detergents approximately 20 proteins were extracted from the cell wall. From seven of these N-terminal amino acid sequences were determined.