Milk, breast

Humans are exposed to pollutants via inhalation, dermal uptake and dietary and nondietary ingestion. In fact, human exposure begins from the womb and continues until death. Since POPs are lipophilic contaminants, they tend to accumulate in large quantities in lipid rich tissues. Their accumulation in human milk has received considerable attention because of 

Tcible 5.5 Comparison of PCBs and organochlorine pesticides (ng/g wet weight) In bivalve molluscs 

Location Year Species PCBs DDTs CHLs HCHs HCB Reference 

Country Year PCBs CHLs DDTs HCHs HCB Reference 

The most reliable study of POPs in breast milk samples from developing countries comes from work carried out by Kunisue and colleagues [103-105,155-157]. Here, samples were collected from across Asia and analyzed within the same laboratory using the same analytical procedures. Their studies revealed that relatively high concentrations of DDT, for example, were found in mothers from Vietnam, China, Cambodia and Malaysia, more than from other countries included in their studies. To compare levels in Asia with other developing countries, selected data from other published studies [103-105,155-164] from the literature have been compiled in Table 5.7. Other countries with elevated levels of DDT in breast milk, as shown in Table 5.7, are Zimbabwe, Mexico and Pakistan, aU countries with a history of widespread usage of DDT in malaria vector and pest control. 

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Uses of lactose production by appHcation include baby and infant formulations (30%), human food (30%), pharmaceuticals (25%), and fermentation and animal feed (15%) (39). It is used as a diluent in tablets and capsules to correct the balance between carbohydrate and proteins in cow-milk-based breast milk replacers, and to increase osmotic property or viscosity without adding excessive sweetness. It has also been used as a carrier for flavorings. 

Phenytoin s absorption is slow and variable yet almost complete absorption eventually occurs after po dosing. More than 90% of the dmg is bound to plasma protein. Peak plasma concentrations are achieved in 1.5—3 h. Therapeutic plasma concentrations are 10—20 lg/mL but using fixed po doses, steady-state levels are achieved in 7—10 days. Phenytoin is metabolized in the fiver to inactive metabolites. The plasma half-life is approximately 22 h. Phenytoin is excreted primarily in the urine as inactive metabolites and <5% as unchanged dmg. It is also eliminated in the feces and in breast milk (1,2). Prolonged po use of phenytoin may result in hirsutism, gingival hyperplasia, and hypersensitivity reactions evidenced by skin rashes, blood dyscrasias, etc... 

Mexifitene is well absorbed from the GI tract and less than 10% undergoes first-pass hepatic metabolism. In plasma, 60—70% of the dmg is protein bound and peak plasma concentrations are achieved in 2—3 h. Therapeutic plasma concentrations are 0.5—2.0 lg/mL. The plasma half-life of mexifitene is 10—12 h in patients having normal renal and hepatic function. Toxic effects are noted at plasma concentrations of 1.5—3.0 lg/mL, although side effects have been noted at therapeutic concentrations. The metabolite, /V-methy1mexi1itene, has some antiarrhythmic activity. About 85% of the dmg is metabolized to inactive metabolites. The kidneys excrete about 10% of the dmg unchanged, the rest as metabolites. Excretion can also occur in the bile and in breast milk (1,2). 

The GI absorption of the dmg after po adrninistration is slow and variable with estimates ranging from 20—55%. Once absorbed, 96% of the dmg is bound to plasma proteins and other tissues on the body. Whereas peak plasma concentrations may be achieved in 3—7 h, the onset of antiarrhythmic action may occur in 2—3 days or more. This may result, in part, from distribution to and concentration of the dmg in adipose tissue, Hver, spleen, and lungs. Therapeutic plasma concentrations are 1—2 p.g/mL, although there appears to be no correlation between plasma concentration and antiarrhythmic activity. The plasma half-life after discontinuation of the dmg varies from 13—103 days. The dmg is metabolized in the Hver and the principal metaboHte is desethylamiodarone. The primary route of elimination is through the bile. Less than 1% of the unchanged dmg is excreted in the urine. The dmg can also be eliminated in breast milk and through the skin (1,2). 

Human exposure to environmental contaminants has been investigated through the analysis of adipose tissue, breast milk, blood and the monitoring of faecal and urinary excretion levels. However, while levels of persistent contaminants in human milk, for example, are extensively monitored, very little is known about foetal exposure to xenobiotics because the concentrations of persistent compounds in blood and trans-placental transmission are less well studied. Also, more information is needed in general about the behaviour of endocrine disruptive compounds (and their metabolites) in vivo, for example the way they bind to blood plasma proteins. 

The CaR regulates numerous biological processes, including the expression of various genes (e.g., PTH) the secretion of hormones (PTH and calcitonin), cytokines (MCP-1), and calcium (e.g., into breast milk) the activities of channels (potassium channels) and transporters (aquaporin-2) cellular shape, motility (of macrophages), and migration cellular adhesion (of hematopoietic stem cells) and cellular proliferation (of colonocytes), differentiation (of keratinocytes), and apoptosis (of H-500 ley dig cancer cells) [3]. 

The GI stimulants are contraindicated in patients witii known hypersensitivity to the drug, GI obstruction, gastric perforation or hemorrhage, or epilepsy. These drugs are secreted in breast milk and should not be used during lactation. 

This section of the chapter discusses FSH, LH, GH, and ACTH. FSH and LH are called gonadotropins because they influence the gonads (the organs of reproduction). GH, also called somatotropin, contributes to the growth of the body during childhood, especially the growth of muscles and bones. ACTH is produced by the anterior pituitary and stimulates the adrenal cortex to secrete the corticosteroids. The anterior pituitary hormone, TSH, is discussed in Chapter 51. Prolactin, which is also secreted by the anterior pituitary, stimulates the production of breast milk in the postpartum patient Additional functions of prolactin are not well understood. Prolactin is the only anterior pituitary hormone that is not used medically. 

Bound glutamates in proteins are very common in food. Human breast milk contains ten times as much as cows milk, and tomato juice contains four times as much as breast milk. However, free glutamate, as found in soy sauce or prepared foods, enters the bloodstream much faster than the glutamates bound in proteins, which are released slowly during digestion. 

Dantrolene is the mainstay of MH treatment. It has long been available for the treatment of muscle spasm in cerebral palsy and similar diseases. It is a hydantoin derivative that was first synthesized in 1967, and reported to be effective in the treatment of porcine MH in 1975. Also in 1975, dantrolene was shown to be more effective than procainamide in the treatment of human MH, which until that time was the drug of choice. However, the intravenous preparation was not made available until November 1979. It significantly lowered mortality. The half-life of dantrolene is estimated to be 6-8 hr. Dantrolene s primary mode of action is the reduction in calcium release by the sarcoplasmic reticulum. Dantrolene also exerts a primary antiarrhythmic effect by increasing atrial and ventricular refractory periods. Side effects of dentrolene include hepatotoxicity, muscle weakness, ataxia, blurred vision, slurred speech, nausea, and vomiting. Dantrolene is not contraindicated in pregnancy, but it does cross into breast milk and its effect on the neonate is unknown. 

Sex and age differences in stable isotopes of nitrogen and carbon are not pronounced. There is no evidence that males and females were eating different foods and the only evidence for age differences, higher 8 N in infants, has been explained by the trophic level shift during the time the infant derives most of its protein from, breast milk. The small amount of variation in both and 5 N values supports the historical sources, which indicate that while food was plentiful, the diet was rather monotonous. 

Children are expected to be exposed to methyl parathion by the same routes that affect adults. Small children are more likely to come into contact with methyl parathion residues that may be present in soil and dust both outside and inside the home, due to increased hand-to-mouth activity and playing habits. Methyl parathion has been detected in a few samples of breast milk, indicating potential for exposure of nursing infants. However, available data are not adequate for determination of the importance of this route of child exposure. 

The available evidence suggests that excretion of methyl parathion metabolites in humans and animals following acute oral exposure is essentially the same and occurs rapidly. Excretion occurs primarily via the urine. Methyl parathion can also be excreted in breast milk, although it has been detected only in a limited number of samples from women of central Asia, for which exposure data were not available (Lederman 1996) (see also Section 3.4.2.2). A study in rats also reported excretion of methyl parathion in the milk (Golubchikov 1991 Goncharuk et al. 1990). 

Additional studies to determine breast milk contamination by methyl parathion are needed to be able to... 

Lederman SA. 1996. Environmental contaminants in breast milk from the central Asian republics. Reprod Toxicol 10(2) 93-104. 

Renal excretion is the most important endosulfan elimination route in humans and animals. Biliary excretion has also been demonstrated to be important in animals. Estimated elimination half-lives ranged between approximately 1 and 7 days in adult humans and animals. Endosulfan can also be eliminated via the breast milk in lactating women and animals, although this is probably a relatively minor elimination route. No studies were located regarding known or suspected differences between children and adults with respect to endosulfan excretion. 

No data were located concerning whether pharmacokinetics of endosulfan in children are different from adults. There are no adequate data to determine whether endosulfan or its metabolites can cross the placenta. Studies in animals addressing these issues would provide valuable information. Although endosulfan has been detected in human milk (Lutter et al. 1998), studies in animals showed very little accumulation of endosulfan residues in breast milk (Gorbach et al. 1968 Indraningsih et al. 1993), which is consistent with the rapid elimination of endosulfan from tissues and subsequent excretion via feces and urine. There are no PBPK models for endosulfan in either adults or children. There is no information to evaluate whether absorption, distribution, metabolism, or excretion of endosulfan in children is different than in adults. 

The developing human s source of nutrition changes with age from placental nourishment to breast milk or formula to the diet of older children who eat more of certain types of foods than adults. A child s behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

Infants are particularly sensitive to endosulfan due to their higher intestinal permeability and immature detoxification system. In a study of human breast milk conducted in the country of Kazakhstan in 1994, the concentration of various contaminants, including endosulfan, were determined (Lutter et al. 1998). 

Of the 91 samples of breast milk analyzed, only 2 had detectable quantities of endosulfan (concentrations not specified). In another study, the transfer of endosulfan and its metabolites were studied in breast milk of lactafing goats (Indraningsih et al. 1993). Endosulfan residues in milk of goats administered a daily dose of 1 mg/kg for 28 days reached 0.02 mg/kg on day 1. However, by day 8, no residues or metabolites could be detected. Likewise, no endosulfan residues could be detected in the tissues of kids except for a-endosulfan in the liver at a concentration of 0.0011 mg/kg. Analysis of milk from cows... 

Lutter C, Iyengar V, Barnes R, et al. 1998. Breast milk contamination in Kazakhstan implications for infant feeding. Chemosphere 37(9-12) 1761-1772. 

Public concern about PBDE levels in the environment was heightened when it was shown that a sharp increase in the concentration of certain PBDEs had occurred in human breast milk over only a 10-year period (Meironyte et al. 1999 Noren and Meironyte 2000), and the levels of exposure in some infants and toddlers were similar to those shown to cause developmental neurotoxicity in animal experiments (Costa and Giordano 2007). As a result of these concerns, the majority of commercial PBDE mixtures have been banned from manufacture, sale, and use within the European Union. 

Hooper, K. and McDonald, T.A. (2000). The PBDEs An emerging environmental challenge and another reason for breast milk monitoring programs. Environmental Health Perspectives 108, 387-392. 

Retroviruses Human T-cell leukaemia virus (HTLV-1) Spherical enveloped virus lOOnm in diameter, icosahedral cores contain two copies of linear RNA molecules and reverse transcriptase HTI.V is spread inside infected lymphocytes in blood, semen or breast milk. Most infections remain asymptomatic but after an incubation period of 10-40 years in about 2% of cases, adult T-cell leukaemia can result... 

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