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See source code for a lot of text from the deleted prenatal meth exposure article. <!-- Prenatal methamphetamine exposure (PME) is the exposure of a fetus to methamphetamine when a woman uses the drug during her pregnancy. Methamphetamine (MA) has shown increasing popularity in the past two decades among women of childbearing age. Methamphetamine is second only to cannabis as the most widely used illegal drug, which may be because it is relatively cheap and easy to manufacture. Yet, to this date, the effects of PME on the developing fetus have not been well characterized and even less is known regarding the effects on development in childhood. Although few studies have established a pattern of MA use in pregnant users, it is important that researchers seek to determine this pattern to examine a possible dose-response relationship between MA use and neonatal outcomes. The recent increase in MA use in the United States, particularly in the South and Midwest, highlights the need for a better understanding of the short-term and long-term effects of MA use during pregnancy upon newborns and young children.

The effects of MA on a fetus are often compared to those of cocaine, but the neurotoxic effects of MA may be greater than those of cocaine. This may be due to MA’s ability to remain active in the body for longer and its greater capacity to mimic the effects of neurotransmitters in the brain. Studying the effects of PME is often complicated by the fact that there are numerous elements that are associated with MA use, which in turn may be associated with adverse effects in exposed infants. For example, depression is highly correlated with MA use, which is in turn associated with less spousal support, increased anxiety, less prenatal care, malnourishment, preterm labor, and more stressors in the areas of work, health, and environment. A study done in New Zealand found that mothers referred to treatment centers for MA use were often multiple drug abusers, had a history of not keeping doctors appointments, and displayed mental health problems including psychotic behavior. This makes it incredibly difficult for researchers to tease apart the effects due to the drug itself versus the other influential lifestyle factors.

Pathophysiology
Methamphetamine (MA), a potent central nervous system stimulant, causes a rush of dopamine, norepinephrine, and serotonin release in the brain when ingested. Street methamphetamine is referred to by many names, such as “speed,” “meth,” and “chalk”. The drug can be injected, smoked, snorted, and even taken by oral or anal routes. The neurotransmitter release from MA ingestion (especially dopamine) leads to feelings of euphoria, decreased appetite and fatigue, and increased alertness, wellbeing, and exhilaration. More specifically, MA mechanism of action is to stimulate the release of dopamine into the synaptic cleft while preventing the reuptake of dopamine and norephinephrine. Long-lasting functional impairments in the monoamine system are likely to result from long-term abuse of MA.

It is known that MA readily crosses the placenta that feeds the developing fetus, yet the ways in which the drug affects the fetus are not fully understood. MA may exert its effects on the fetus directly by transfer through the placenta or indirectly by altering the fetal environment. MA has vasoconstrictive effects, resulting in decreased uteroplacental blood flow, elevated fetal blood pressure, and fetal hypoxia. These effects often work together to result in prenatal strokes, heart or other major organ damage in the developing fetus. These vasoconstrictive side effects can also have anorexic effects on the mother, which can hinder intrauterine growth. Studies done with pregnant rodents have found that prenatal MA exposure results in altered neural circuitry, both structurally and functionally. These impairments can lead to later behavioral problems since the neural circuitry is responsible for maintaining functions such as arousal, regulation and reactivity to stress.

Effects and prognosis
Thus far, only three areas of research have garnered a limited amount of information regarding the effects of prenatal MA use on developing children, which include animals studies, a minimal number of human studies that have many limitations, and the recent cocaine literature. Though in recent years conducted by Pedro Melo, Vincente Zanon Moreno, Sheila Pons Vazquez, Maria Dolores Pinazo-Duran, Maria Amelia Tavares for the Institute of Molecular and Cell Biology, Porto, Portugal researched rats who were exposed to MA use and its effects on the optic nerve myelination after prenatal exposure to this psycho-stimulant. It is known that MA use effects sensory systems and the optic nerve according to the results of this study proved to be a target tissue. It is often difficult to isolate psycho-stimulant use because often, the abusers of these substances are polydrug users, so animal studies are the closest thing to isolating the effects of just one psycho-stimulant. The Optic Nerve is suitable structure to look at because it is a well studied structure and homogeneous between species. At birth, for most species, the Optic Nerve is unmyelinated, but that changes with adulthood and most of the nerve becomes myelinated. In this study they gave doses of 5 mg/day from days 8 to 22 of pregnancy. The offspring were sacrificed at days 7,14, and 21. The treated MA group males had significantly smaller optic nerve diameter. The Optic Nerve area PND21 was significantly smaller than the unexposed control group. The cross section at this area also was significantly smaller. The final results concluded that there was an 80% increase in myelination on day 21, but only the female group. This is consistent with rapid aging of the Optic Nerve due to MA exposure. Western Blotting showed that postnatal days of 14 and 21 female group showed lower myelination basic protein level compared to the same control age group. Though this study was conducted with the use of rats there is a high degree of similarity to rat and human anatomy, so this can be comparable to effects on humans. This cannot be confirmed though until MA exposed humans are studied postmortem. These studies, just as those of early prenatal cocaine exposure research, have a number of methodological problems that include small sample size and confounding due to maternal use of a variety of drugs. Yet, MA use in utero is believed to affect the development of a baby’s brain, spinal cord, heart, and kidney. Studies have found short-term symptoms to include prenatal complications, such as premature delivery and birth deformities, along with strokes and brain hemorrhages prior to birth. Other investigations have revealed short-term neonatal outcomes to include small deficits in infant neurobehavioral function and growth restriction when compared to control infants. Also, prenatal MA use is believed to have long-term effects in terms of brain development, which may last for many years.

Mental, emotional, and behavioral outcomes
A limited amount of research exists that focuses on the possible cognitive, language, motor, emotional, and behavioral functioning of young children prenatally exposed to methamphetamine. Newborns prenatally exposed to MA often experience sleep disturbances and altered behavior problems since MA mimics neurotransmitters in the brain. One-year-old children prenatally exposed to MA have been shown to exhibit poorer fine motor performance, which is associated with their visual perceptual and spatial skills. This has the possibility to hinder future visual perceptual processing, thereby making it more difficult for these children to carry out coordinated movements, such as bicycle riding and other physically demanding activities. A physician from Iowa, Dr. Rizwan Shah, found that once babies exposed to methamphetamines prenatally hit about three to four weeks old, they show signs of irritability that may last for years and eat poorly, despite their need for nutrients and calories. Once these babies become school-aged children, they are more likely to be hyperactive or to have attention deficit hyperactivity disorder (ADHD), learning disabilities, and unprovoked fits of anger.

In order to gain insight into the long-term effects of prenatal methamphetamine exposure, a study undertaken in Sweden carried out developmental assessments of children from birth to 14 years old, who were born to mothers that abused MA during their pregnancy. They found that 8-year-olds displayed aggressive behavior and social adjustment issues, which were positively associated with the amount and duration of methamphetamine exposure in utero. By age 14, their language acquisition, athletic abilities, and mathematic skills were statistically lower than those of their classmates. However, it is likely that psychosocial factors related to their environment, such high numbers of foster care placements, stress, and overcrowded living conditions, played a significant role in their behavioral and academic outcomes. Mothers who continue to abuse methamphetamine after giving birth often expose their children to physical and family environments that are chaotic, neglectful, and abusive. In addition, these women often report having less control over their children and see their children as being more aggressive. Researchers believe these behavioral problems associated with prenatal drug exposure are intensified by the children’s’ high stress postnatal environments. Other studies have found that children who remain in the care of addicted parents are more likely to display behavioral and emotional disturbances than those whose parents quit abusing the drug. Ultimately, more research needs to be conducted regarding the developmental outcomes for children prenatally exposed to MA, since this area of research remains widely unknown. In addition, it is unclear if the symptoms previously discovered are due to actual drug exposure in utero or to their home environment.

Social stigma
Media and social policy have contributed to an environment that stigmatizes pregnant substance abusers as shameful, corrupt persons who are unfit to be mothers. Unfortunately, this stigmatization has also crossed over into research, which is often influenced by biases, assumptions, and subjective judgments. Much of the data that currently exists on prenatal meth exposure comes from unsubstantiated findings and poorly conducted studies that exaggerate the effects of illicit substance abuse. Prenatal drug use by women in the United States came to the forefront of media and public health attention in the 1980s when cheap crack cocaine became widely available. The media portrayed pregnant crack abusers to be poor African Americans and Latinas who contributed to increased gang violence, expanding underclass, and an overwhelming number of ‘crack babies’. As a result, these women often faced legal ramifications such as loss of parental rights to their children due to charges of neglect and abuse, reduction in welfare benefits, and imprisonment. Although there was legitimate cause for concern as to the potential developmental and behavioral outcomes of children prenatally exposed to drugs, the media created an image of these babies as ‘damaged for life’. However, the evidence used to support the notion that crack babies were ultimately doomed came from methodologically compromised studies and anecdotal reports.

Treatment and prevention
Methamphetamine is a highly addictive drug that can make users crave more as soon as the end of the last dose, which makes it difficult for them to quit on their own. In addition, when meth users attempt to quit, they often experience intense and uncomfortable withdrawal symptoms, such as anxiety, excessive eating and sleeping, depression, and intense cravings. However, it is possible for women to successfully treat their addiction during pregnancy, with the most beneficial outcomes for the baby occurring when treatment begins in the first trimester. Methamphetamine addiction treatment centers can help pregnant women safely detoxify with the use of medications that can eliminate withdrawal symptoms, followed by psychiatric and obstetric evaluation and care. In addition, many treatment programs offer individual and group counseling sessions to teach future mothers how to cope with stress without relapsing.

Raising awareness as to the extent of the meth abuse problem, in combination with prevention techniques, is a key way to address the developmental and behavioral needs of children prenatally exposed to meth. Increased awareness involves proactive education by health professionals about the severity of the problem and fostering skills to recognize methamphetamine users. These adjustments can allow for immediate intervention and possible protection of the unborn child. In addition, there are other resources that are in place to raise awareness of the issue, promote prevention, and offer possible treatment options. For example, The State of Montana’s Office of Public Instruction Web site offers a methamphetamine prevention curriculum to middle school students, while the UCLA Integrated Substances Abuse program sponsors a Web site on the delivery of treatment services for methamphetamine. Also, a children’s hospital in Rhode Island established the Vulnerable Infants Program to aid the court in making decisions regarding drug-exposed infants possible placement in foster care and treatment options. The program also places an emphasis on trying to help families stay together when appropriate. This is an example of how collaborative effects can be made between the justice system and the health care community to ensure the wellbeing of children.

From Histone
The common nomenclature of histone modifications is:
 * The name of the histone (e.g., H3)
 * The single-letter amino acid abbreviation (e.g., K for Lysine) and the amino acid position in the protein
 * The type of modification (Me: methyl, P: phosphate, Ac: acetyl, Ub: ubiquitin)
 * The number of modifications (only Me is known to occur in more than one copy per residue. 1, 2 or 3 is mono-, di- or tri-methylation)

So H3K4me1 denotes the monomethylation of the 4th residue (a lysine) from the start (i.e., the N-terminal) of the H3 protein.

From Histone code

 * H3K4me3 is enriched in transcriptionally active promoters.
 * H3K9me3 is found in constitutively repressed genes.
 * H3K27me3 is found in facultatively repressed genes.
 * H3K36me3 is found in actively transcribed gene bodies.
 * H3K9ac is found in actively transcribed promoters.
 * H3K14ac is found in actively transcribed promoters.
 * H3K27ac distinguishes active enhancers from poised enhancers.
 * H3K122ac is enriched in poised promoters and also found in a different type of putative enhancer that lacks H3K27ac.

List of new modifications to add and existing modifications to update when merging
H2A
 * Humans
 * H2AK5ac - Transcriptional activation (Hs)

H2B
 * H2BK5ac - Transcriptional activation (Hs)

H3
 * Lysine residue 4:
 * H3K4me1 - Transcriptional activation (Hs)
 * H3K4me2 - Transcriptional activation (Hs)
 * H3K4me3 - Transcriptional activation (Hs)
 * Lysine residue 9:
 * H3K9me1 - Transcriptional repression (Hs) via G9a and G9a-like protein
 * H3K9me2 - Transcriptional repression (Hs) via G9a, G9a-like protein, and SETDB1
 * H3K9me3 - Transcriptional repression (Hs) via SETDB1
 * H3K9ac - Transcriptional activation (Saccharomyces cerevisiae)/Nuclear receptor coactivation (Hs) via SETDB1
 * Lysine residue 27:
 * H3K27me1 - ...
 * H3K27me2 - ...
 * H3K27me3 - ...
 * Quote from a source on H3K4, H3K9, and H3K27 mono/di/tri-methylation states: It needs to be kept in mind that methylation of histone H3K4 is generally associated with increased transcriptional activity [45] whereas methylation of H3K9 and H3K27 is associated with repression of gene expression [44, 46].
 * H3K27ac-See "Other organisms"
 * Lysine residue 14:
 * H3K14ac - Transcriptional activation (Hs)
 * Lysine residue 36:
 * H3K36me1 - Transcription activation (Hs)
 * H3K36me2 - Transcription activation (Hs) in Saccharomyces cerevisiae, H3K36me2 is associated with gene repression
 * H3K36me3 - Transcription activation (Hs)
 * Arginine residue 8:
 * H3R8me1 - Transcriptional repression (Hs) via PRMT5
 * H3R8me2s (symmetric dimethylation) - Transcriptional repression (Hs) via PRMT5

Arginine residue 17:
 * H3R17me1 - Transcriptional activation (Hs)
 * H3R17me2a (w/ H3K18ac and H3K23ac) - Transcriptional activation (Hs) (I'm assuming me2a means dimethyl-acetylation)
 * H3K18ac (via p300, w/o other marks) - Transcriptional activation (Hs)
 * H3K18ac (via CBP, with H3R17me2 and H3K23ac) - Transcriptional activation (Hs)
 * H3K23ac (via CBP, with H3R17me2 and H3K18ac) - Transcriptional activation (Hs)


 * Serine residue 10 phosphorylation:


 * H3S10ph - Transcriptional activation (in general in Sc, of IEGs in Hs) / upregulation (Hs)
 * quote from another source: One of the best-characterized histone phosphorylation sites is serine 10 on histone H3 (H3S10).This modification stabilizes the HAT, GCN5, on associated gene promoters while antagonizing the repressive modification - methylation of lysine 9 on histone H3 (H3K9) and its subsequent recruitment of HP1 (heterochromatin protein 1, see below).6 Since phosphorylation at H3S10 recruits a HAT, the neighboring lysine residue at H3K9 is often acetylated in concert with phosphorylation, a process called phosphoacetylation that further potentiates gene activation.

H2A H2B H3
 * Other organisms
 * H2AK7ac - Transcriptional activation (Saccharomyces cerevisiae)
 * H2AK126su - Transcriptional repression; Blocks Histone acetylation and histone ubiquitination (Saccharomyces cerevisiae) (su: sumoylation)
 * H2BK16su - Gene repression (Saccharomyces cerevisiae)
 * H2BK17su - Gene repression (Saccharomyces cerevisiae)
 * H2BK34ub - Transcriptional activation (Saccharomyces cerevisiae) (ub: ubiquitination)
 * H3K4ac - Transcription activation at some promoters (Saccharomyces cerevisiae)
 * H3K27ac - "Enhancer function, gene expression" (Saccharomyces cerevisiae, Drosophila melanogaster) (I guess this essentially means transcriptional activation)