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At least 703 records · Page 39Linked to original sources
PubMed2004

Maternal dietary vitamin restriction increases body fat content but not insulin resistance in WNIN rat offspring up to 6 months of age.

AIMS/HYPOTHESIS: Epidemiological evidence suggests that some adult diseases like insulin resistance syndrome and diseases associated with it originate in fetal life. The role of maternal macronutrient malnutrition but not of micronutrients in the fetal origin of adult disease is well studied. We hypothesise that chronic maternal vitamin restriction predisposes the offspring to insulin resistance syndrome. METHODS: Female weanling Wistar/NIN rats received a control diet ( n=6) or a 50% vitamin-restricted diet ( n=14) for 12 weeks and mated with control males. Four dams on the restricted diet were shifted to the control diet from parturition. Pups born to the remaining 10 dams on the restricted diet were weaned on to control diet or continued on the restricted diet. All groups had 8 male pups from weaning onwards. RESULTS: Birthweights of pups were comparable among different groups. Weaning body weights were low in the restricted diet group, but on rehabilitation they caught up with control animals by post-natal day 100. None of the pups had impaired oral glucose tolerance and their insulin resistance status was comparable on days 40, 70, 100 and 180. Compared with offspring on the control diet, offspring on the restricted diet had a significantly higher percentage of body fat and higher plasma triglycerides, as well as lower lean body mass and fat-free mass. They also had increased oxidative stress. Rehabilitation from parturition or weaning prevented the changes in body fat percent, lean body mass, fat-free mass and oxidative stress. CONCLUSIONS/INTERPRETATION: Since changes in adiposity and fat metabolism are considered forerunners of insulin resistance syndrome, our observations suggest that maternal dietary vitamin restriction predisposes the offspring to insulin resistance syndrome in later life.

Adipose Tissue↗
PubMed2005

Clinical application of a semimechanistic-physiologic population PK/PD model for neutropenia following pemetrexed therapy.

PURPOSE: The objective of these analyses was to examine the effect of variations in the explanatory factors of neutropenic response, identified by semimechanistic-physiologic population pharmacokinetic/pharmacodynamic (PK/PD) modeling, on clinically important features of the absolute neutrophil count (ANC)-time profile (e.g, the nadir of the ANC [NANC], its timing [T (Nadir)], and the timecourse of recovery [T (Rec)]). METHODS: Correlation analyses were used to evaluate the relationship of NANC, T (Nadir), and T (Rec) as a function of overall systemic exposure (AUC) and each of the covariates contained in the population PK/PD model. Simulations using the final PK/PD model were used to generate complete ANC-time profiles. Frequency counts of NANCs from the simulated profiles were used to quantitatively explore differences in the incidence and severity of neutropenia associated with a variety of scenarios (500 mg/m2 versus 600 mg/m2, normal vitamin deficiency markers versus elevated vitamin deficiency markers, and body surface area-based versus renal function-based dosing) and to evaluate the effect of individual explanatory factors with respect to neutropenic response. RESULTS: Information obtained from correlation analysis and simulations was helpful in quantitatively exploring the impact of dose, exposure, and/or patient characteristics on neutropenic response. The information gained from these simulations provided supportive evidence for the decision to routinely include vitamin supplementation during pemetrexed treatment as a means of managing the risk of severe neutropenia secondary to pemetrexed administration. These techniques also provided information regarding the specific T (Nadir) and T( Rec) for inclusion in product labeling and suggested that a 14-day treatment cycle might be feasible for pemetrexed. CONCLUSION: For population PK/PD models, to provide useful information for the practicing clinician or the clinical development team, it is not sufficient to look only at influences of covariates on model parameters. Rather, the modeling results need to be carefully investigated in terms of clinically relevant measures.

Adult↗
PubMed2005

A semimechanistic-physiologic population pharmacokinetic/pharmacodynamic model for neutropenia following pemetrexed therapy.

PURPOSE: The objectives of these analyses were to (1) develop a semimechanistic-physiologic population pharmacokinetic/pharmacodynamic (PK/PD) model to describe neutropenic response to pemetrexed and to (2) identify influential covariates with respect to pharmacodynamic response. PATIENTS AND METHODS: Data from 279 patients who received 1,136 treatment cycles without folic acid or vitamin B12 supplementation during participation in one of eight phase II cancer trials were available for analysis. Starting doses were 500 or 600 mg pemetrexed per m2 body surface area (BSA), administered as 10-min intravenous infusions every 21 days (1 cycle). The primary analyses included 105 patients (279 cycles) for which selected covariates-including vitamin deficiency marker data (i.e., homocysteine, cystathionine, methylmalonic acid, and methylcitrate [I, II, and total] plasma concentrations)-were available. Classical statistical multivariate regression analyses and a semimechanistic-physiologic population PK/PD model were used to evaluate neutropenic response to single-agent pemetrexed administration. RESULTS: The timecourse of neutropenia following single-agent pemetrexed administration was adequately described by a semimechanistic-physiologic model. Population estimates for system-based model parameters (i.e., baseline neutrophil count, mean transit time, and the feedback parameter), which mathematically represent current understanding of the process and physiology of hematopoiesis, were consistent with previously reported values. The population PK/PD model included homocysteine, cystathionine, albumin, total protein, and BSA as covariates relative to neutropenic response. CONCLUSION: These results support the programmatic decision to introduce folic acid and vitamin B12 supplementation during pemetrexed clinical development as a means of normalizing patient homocysteine levels, thereby managing the risk of severe neutropenia secondary to pemetrexed administration. The current results also suggest that the addition of vitamin B6 supplementation to normalize patient cystathionine levels may further decrease the incidence of grade 4 neutropenia following pemetrexed administration. The results also suggest the use of folic acid as a means of lessening hematologic toxicity following administration of cytotoxic agents other than antifolates.

Adult↗
PubMed2003

Micronutrient deficiencies. Hohenheim Consensus Conference.

OBJECTIVE: The aim of this study was to consider the risk of micronutrient deficiencies and approaches for intervention, and to summarize existing knowledge and identify areas of ignorance. DESIGN: Experts from a range of relevant disciplines received and considered a series of questions related to aspects of the topic. INTERVENTION: The experts met and discussed the questions and arrived at a consensus. CONCLUSION: Though healthy balanced diet is available for the general European population, a few defined groups are at risk of micronutrient deficiencies. In addition, the intake of specific micronutrients such as iron, folic acid, vitamin D and vitamin B12 are often marginal. To overcome these deficiencies, either selected micronutrients or a mixture of different micronutrients might be recommended. However, to define and detect micronutrient deficiencies, specific biomarkers are only available for a few micronutrients (e. g. vitamin D, folic acid, vitamin C, iron). The definition of a risk group, based on scientific data, might be an appropriate way to justify intervention with supplements.

Aging↗
PubMed1981

Premenstrual syndrome.

The premenstrual syndrome (PMS) is a major clinical entity afflicting a large segment of the female population. Available information are descriptive in nature and the etiology of this syndrome remains unclear. In this review, both biochemical and psychosocial elements of the syndrome have been explored in an effort to redefine the pathophysiology of this seemingly multifactorial psychoneuroendocrine dysfunction. We propose that luteal phase sensitivity to and subsequent withdrawal from the central effects of the neuropeptides beta-endorphin and alpha-melanocyte-stimulating hormone result in a cascade of neuroendocrine changes within the brain-hypothalamus-pituitary complex. Modulation of neurotransmitter function by these peptides may produce alterations in mood and behavior as well as enhance pituitary release of prolactin and vasopressin. Variable gonadal steroid modulation of these responses from subject to subject likely accounts for the heterogeneous clinical manifestations of the PMS.

Adult↗
PubMed1985

Nutritional status of patients with untreated cervical cancer. II. Vitamin assessment.

Prospective vitamin assessment was undertaken in 78 patients with untreated cancer of the uterine cervix. At least one abnormal vitamin level was present in 67% of patients while individual levels were abnormal in as many as 38% of patients. Significantly lowered levels of plasma folate, vitamin A, and vitamin C were present. Although most of these vitamins did not correlate with other parameters of protein-calorie malnutrition, the possible preventative and treatment effects of these vitamins require additional investigation.

Avitaminosis↗