The effects of surgery on plasma/serum vitamin C concentrations: a systematic review and meta-analysis.

Vitamin C (ascorbic acid) is a water-soluble vitamin with an array of biological functions. A number of proposed factors contribute to the vitamin's plasma bioavailability and ability to exert optimal functionality. The aim of this review was to systematically assess plasma vitamin C levels post-surgery compared with pre-surgery/the magnitude and time frame of potential changes in concentration. We searched the PUBMED, SCOPUS, SciSearch and the Cochrane Library databases between 1970 and April 2020 for relevant research papers. Prospective studies, control groups and true placebo groups derived from controlled trials that reported means and standard deviations of plasma vitamin C concentrations pre- and postoperatively were included into the meta-analysis. Data were grouped into short-term (≤7 d) and long-term (>7 d) postoperative follow-up. Twenty-three of thirty-one studies involving 642 patients included in the systematic review were suitable for meta-analysis. Pooled data from the meta-analysis revealed a mean depletion of plasma vitamin C concentration of -17·99 µmol/l (39 % depletion) (CI -22·81, -13·17) (trial arms = 25, n 565, P < 0·001) during the first postoperative week and -18·80 µmol/l (21 % depletion) (CI -25·04, -12·56) (trial arms = 6, n 166, P < 0·001) 2-3 months postoperatively. Subgroup analyses revealed that these depletions occurred following different types of surgery; however, high heterogeneity was observed amongst trials assessing concentration change during the first postoperative week. Overall, our results warrant larger, long-term investigations of changes in postoperative plasma vitamin C concentrations and their potential effects on clinical symptomology.

Aged garlic extract reduces blood pressure in hypertensives: a dose-response trial.

BACKGROUND/OBJECTIVES: Hypertension affects about 30% of adults worldwide. Garlic has blood pressure-lowering properties and the mechanism of action is biologically plausible. Our trial assessed the effect, dose-response, tolerability and acceptability of different doses of aged garlic extract as an adjunct treatment to existing antihypertensive medication in patients with uncontrolled hypertension. SUBJECTS/METHODS: A total of 79 general practice patients with uncontrolled systolic hypertension participated in a double-blind randomised placebo-controlled dose-response trial of 12 weeks. Participants were allocated to one of three garlic groups with either of one, two or four capsules daily of aged garlic extract (240/480/960 mg containing 0.6/1.2/2.4 mg of S-allylcysteine) or placebo. Blood pressure was assessed at 4, 8 and 12 weeks and compared with baseline using a mixed-model approach. Tolerability was monitored throughout the trial and acceptability was assessed at 12 weeks by questionnaire. RESULTS: Mean systolic blood pressure was significantly reduced by 11.8±5.4 mm Hg in the garlic-2-capsule group over 12 weeks compared with placebo (P=0.006), and reached borderline significant reduction in the garlic-4-capsule group at 8 weeks (-7.4±4.1 mm Hg, P=0.07). Changes in systolic blood pressure in the garlic-1-capsule group and diastolic blood pressure were not significantly different to placebo. Tolerability, compliance and acceptability were high in all garlic groups (93%) and highest in the groups taking one or two capsules daily. CONCLUSIONS: Our trial suggests aged garlic extract to be an effective and tolerable treatment in uncontrolled hypertension, and may be considered as a safe adjunct treatment to conventional antihypertensive therapy.

The anti-mutagenic properties of bile pigments.

Bile pigments, including bilirubin and biliverdin, are endogenous compounds belonging to the porphyrin family of molecules. In the past, bile pigments and bilirubin in particular were thought of as useless by-products of heme catabolism that can be toxic if they accumulate. However, in the past 20 years, research probing the physiological relevance of bile pigments has been mounting, with evidence to suggest bile pigments possess significant antioxidant and anti-mutagenic properties. More specifically, bile pigments are potent peroxyl radical scavengers and inhibit the mutagenic effects of a number of classes of mutagens (polycyclic aromatic hydrocarbons, heterocyclic amines, oxidants). Coincidentally, persons with elevated circulating bilirubin concentrations have a reduced prevalence of cancer and cardio-vascular disease. Despite the encouraging in vitro anti-mutagenic effects of bile pigments, relatively little research has been conducted on their inhibitory capacity in bacterial and cultured cell assays of mutation, which might link the existing in vitro and in vivo observations. This is the first review to summarise the published data and it is our hope it will stimulate further research on these potentially preventative compounds.

The anti-mutagenic and antioxidant effects of bile pigments in the Ames Salmonella test.

The aim of this study was to explore the potential pro- and anti-mutagenic effects of endogenous bile pigments unconjugated bilirubin (BR), biliverdin (BV) and a synthetic, water soluble conjugate, bilirubin ditaurate (BRT) in the Ames Salmonella test. The bile pigments were tested over a wide concentration range (0.01-2 micromol/plate) in the presence of three bacterial strains (TA98, TA100, TA102). A variety of mutagens including benzo[alpha]pyrene (B[alpha]P), 2,4,7 trinitrofluorenone (TNFone), 2-aminofluorene (2-AF), sodium azide (NaN(3)) and tertiary-butyl hydroperoxide (t-BuOOH), were used to promote the formation of mutant revertants. Tests were conducted with (B[alpha]P, 2-AF, t-BuOOH) and without (TNFone, NaN(3), t-BuOOH) metabolic activation incorporating the addition of the microsomal liver preparation, S9. The bile pigments alone did not induce mutagenicity in any of the strains tested (p>0.05). Anti-mutagenic effects of the bile pigments were observed in the presence of all mutagens except for NaN(3) and the anti-mutagenic effects appeared independent of the strain tested. For TNFone induced genotoxicity, the order of effectiveness was BR> or =BRT>BV. However, the order was BV> or =BRT> or =BR for 2-AF. Antioxidant testing in the TA102 strain revealed bile pigments could effectively inhibit the genotoxic effect of t-BuOOH induced oxidative stress. The apparent antioxidant and anti-mutagenic behaviour of bile pigments further suggests their presence in biological systems is of possible physiological importance.

Cancer: impact of nutrition intervention outcome--nutrition issues for patients.

OBJECTIVE: We examined nutritional issues, assessment, and intervention strategies for patients with cancer. METHODS: Reviews of practice guidelines and published reports were used to identify nutritional issues and strategies that can benefit patients with cancer. RESULTS: Assessment tools such as the Patient-Generated Subjective Global Assessment are useful in terms of identifying patients with nutrition issues and guiding intervention. However, quality of life and other measures should also be considered. There is a need for early and ongoing nutrition interventions. CONCLUSIONS: Encourage patients to try a new food or supplement on days when they are not receiving chemotherapy or radiation therapy because it may result in better tolerance. Screen patients to determine their nutritional status. Closely monitor changes in weight, food intake, and symptoms such as nausea and vomiting. Refer to a registered dietitian for a complete nutrition assessment and individualized counseling.

Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells.

Fluorescence in situ hybridization of a tile path of DNA subclones has previously enabled the cyto-genetic definition of the minimal DNA sequence which spans the FRA16D common chromosomal fragile site, located at 16q23.2. Homozygous deletion of the FRA16D locus has been reported in adenocarcinomas of stomach, colon, lung and ovary. We have sequenced the 270 kb containing the FRA16D fragile site and the minimal homozygously deleted region in tumour cells. This sequence enabled localization of some of the tumour cell breakpoints to regions which contain AT-rich secondary structures similar to those associated with the FRA10B and FRA16B rare fragile sites. The FRA16D DNA sequence also led to the identification of an alternatively spliced gene, named FOR (fragile site FRA16D oxidoreductase), exons of which span both the fragile site and the minimal region of homozygous deletion. In addition, the complete DNA sequence of the FRA16D-containing FOR intron reveals no evidence of additional authentic transcripts. Alternatively spliced FOR transcripts (FOR I, FOR II and FOR III) encode proteins which share N-terminal WW domains and differ at their C-terminus, with FOR III having a truncated oxidoreductase domain. FRA16D-associated deletions selectively affect the FOR gene transcripts. Three out of five previously mapped translocation breakpoints in multiple myeloma are also located within the FOR gene. FOR is therefore the principle genetic target for DNA instability at 16q23.2 and perturbation of FOR function is likely to contribute to the biological consequences of DNA instability at FRA16D in cancer cells.

Chromosomal fragile site FRA16D and DNA instability in cancer.

It has been proposed that common aphidicolin-inducible fragile sites, in general, predispose to specific chromosomal breakage associated with deletion, amplification, and/or translocation in certain forms of cancer. Although this appears to be the case for the fragile site FRA3B and may be the case for FRA7G, it is not yet clear whether this association is a general property of this class of fragile site. The major aim of the present study was to determine whether the FRA16D chromosomal fragile site locus has a role to play in predisposing DNA sequences within and adjacent to the fragile site to DNA instability (such as deletion or translocation), which could lead to or be associated with neoplasia. We report the localization of FRA16D within a contig of cloned DNA and demonstrate that this fragile site coincides with a region of homozygous deletion in a gastric adenocarcinoma cell line and is bracketed by translocation breakpoints in multiple myeloma, as reported previously (Chesi, M., et al., Blood, 91: 4457-4463, 1998). Therefore, given similar findings at the FRA3B and FRA7G fragile sites, it is likely that common aphidicolin-inducible fragile sites exhibit the general property of localized DNA instability in cancer cells.

Physical assignment of the bovine MHC class IIa and class IIb genes.

Screening of a bovine yeast artificial chromosome (YAC) library revealed two clones which contain most of the class II genes of the major histocompatibility complex (MHC) known to date. The YACs were mapped by fluorescence in situ hybridization (FISH) and characterized for the class II genes they contain. We found that the classic class II genes BoLA- DQA, -DQB, -DRA, and -DRB3 are located at BTA 23q21 and the non-classic class II genes DYA, DIB, LMP2, LMP7, TAP2, BoLA-DOB, -DMA, -DMB, and -DNA are located at BTA 23q12-->q13. These two different mapping locations confirm and extend previous findings of a gross physical distance between classic and non-classic MHC class II genes in cattle.

Gene duplications as a recurrent theme in the evolution of the human pseudoautosomal region 1: isolation of the gene ASMTL.

We have isolated a novel gene, ASMTL (acetylserotonin methytransferase-like ), in the pseudoautosomal region (PAR1) on the human sex chromosomes. ASMTL represents a unique fusion product of two different full-length genes of different evolutionary origin and function. One part is homologous to the bacterial maf/orfE genes. The other part shows significant homology to the entire open reading frame of the previously described pseudoautosomal gene ASMT, encoding the enzyme catalysing the last step in the synthesis of melatonin. We have also detected the identity of one exon (1A) of ASMT to exon 3 in yet another pseudoautosomal gene, XE7. The data presented suggest that exon duplication and exon shuffling as well as gene fusion may represent common characteristics in the pseudoautosomal region.

Double-strand breaks on YACs during yeast meiosis may reflect meiotic recombination in the human genome.

Meiotic recombination in the yeast Saccharomyces cerevisiae is initiated at double-strand breaks (DSBs), which occur preferentially at specific locations. Genetically mapped regions of elevated meiotic recombination ('hotspots') coincide with meiotic DSB sites, which can be identified on chromosome blots of meiotic DNA (refs 4,5; S.K. et al., manuscript submitted). The morphology of yeast artificial chromosomes (YACs) containing human DNA during the pachytene stage of meiosis resembles that of native yeast chromosomes. Homologous YAC pairs segregate faithfully and recombine at the high rates characteristic of S. cerevisiae (vs. approximately 0.4 cM/kb in S. cerevisiae versus approximately 10-3 cM/kb in humans). We have examined a variety of YACs carrying human DNA inserts for double-strand breakage during yeast meiosis. Each YAC has a characteristic set of meiotic DSB sites, as do yeast chromosomes (S.K. et al., manuscript submitted). We show that the positions of the DSB sites in the YACs depend on the human-derived DNA in the clones. The degree of double-strand breakage in yeast meiosis of the YACs in our study appears to reflect the degree of meiotic recombination in humans.

Characterization of a YAC contig spanning the pseudoautosomal region.

Due to its unique biology of partial sex linkage and high recombination rates, the pseudoautosomal region (PAR1) on both X and Y chromosomes has attracted considerable interest. In addition, an extremely high level of YAC instability has been observed in this region. We have derived 82 YAC clones from six different YAC libraries mapping to this 2.6-Mb region. Of these a subset of 22 YACs was analyzed in detail. YAC contigs were assembled using 67 pseudoautosomal probes, of which 64 were unambiguously ordered. All markers are well distributed over the entire region, including the middle part of the region, which has previously been found difficult to contig. Two gaps of less than 50 kb within the genomic locus of CSF2RA and around XE7 remain, which could not be covered with YACs, cosmids, or phages. This YAC contig anchored on the physical map of PAR1 represents one of the best characterized large regions of the human genome with a map completion greater than 90% at 100-kb resolution and has permitted the accurate localization of all known genes within this region.