Rectifying cow infertility under heat stress by immunization against inhibin and supplementation of progesterone.

This study was undertaken for the development of novel techniques that are based on immunoneutralization of inhibin bioactivity to improve Holstein cow fertility. A series of 4 experiments were carried out on 2 farms that were located in subtropical or temperate regions, to test the effects of immunization against inhibin alpha subunit on cow fertility under varying degrees of heat stress conditions. Though immunization against inhibin alone improved conception rate (CR) after TAI moderately in cows under mild heat stress conditions, the treatment plus progesterone supplementation substantially enhanced CR in the range of 25 to 35 percentages from severe heat stress to comfortable weather conditions. There existed an additive effect between immunization against inhibin and progesterone supplementation that maximally enhanced CR. Further, immunization against inhibin increased both FSH and activin A concentrations in blood during both follicular and luteal phases. It also significantly increased blood concentrations of E2 in the follicular phase but decreased P4 concentrations during the early pregnancy. However, interferon-tau concentrations in blood around the time of pregnancy recognition were doubled in the inhibin immunized cows. In conclusion, immunization against inhibin plus P4 treatment enhances ovarian follicle and the subsequent early embryo developments that help to greatly improve the fertility of Holstein dairy cows.

Converging dopaminergic neurotoxicity mechanisms of antipsychotics, methamphetamine and levodopa.

OBJECTIVE: Drugs affecting dopaminergic neurotransmission may exert toxic and beneficial effects that persist after discontinuation by modulating gene expression in key brain regions. Drug addiction, cravings and the tardive symptoms associated with chronic exposure to antipsychotics are among the most common processes attributed to long-term dopaminergic neurotoxicity. The purpose of this review was to investigate the mechanisms of dopaminergic neurotoxicity induced by neuroleptic drugs, dopamine agonists, levodopa, stimulants and known dopaminergic neurotoxins MATERIALS AND METHODS: A PubMed search for each of the dopaminergic compounds in question was carried out. The heterogenous nature of the relevant preclinical studies precluded a systematic review, so a narrative review was carried out. RESULTS: The dopaminergic neurotoxins 6-oxidopamine and 1-methyl-4-phenyl-tetrahydropyridine (MPTP) promote oxidative stress and inhibit mitochondrial function, while their affinity for the dopamine transporter ensures they are attain toxic intracellular concentrations exclusively in dopaminergic neurons. Stimulants which inhibit the vesicular monoamine transporter such as amphetamine and its derivatives promote oxidative stress by greatly increasing intracellular dopamine concentrations and enabling dopamine autooxidation. Antipsychotics increase dopamine release and turnover by blocking autoinhibitory D2 receptors and lead to upregulation of post-synaptic D2 receptors. Dopamine agonists may slow the progression of Parkinson's disease by reducing dopamine turnover, but downregulation of D2 receptors may underlie their behavioural toxicity. CONCLUSIONS: Though the mechanisms have not been completely elucidated yet, it seems drugs which affect dopaminergic neurotransmission may exert long-term effects which reverse slowly upon discontinuation, if at all. Until the nature of these changes is clear it would be best to utilize drugs which affect dopaminergic neurotransmission cautiously especially if prolonged treatment is required.

Efavirenz as a psychotropic drug.

OBJECTIVE: Antiretroviral drugs are the mainstay of treatment for human immunodeficiency virus (HIV) infection. Lifelong highly active antiretroviral therapy (HAART) is indicated to prevent disease progression to acquired immunodeficiency syndrome (AIDS). Efavirenz was a first-line component of HAART across the world for many years. The purpose of this article is to review the psychotropic properties of efavirenz, which are the most important adverse events associated with the drug and commonly result in treatment discontinuation. MATERIALS AND METHODS: A PubMed search was conducted using efavirenz as a search term, which returned 4655 results. Titles and abstracts of articles were screened for relevance, and all relevant articles published in English were included in the narrative review. RESULTS: Acute exposure to efavirenz may cause profound perceptual disturbances (delusions and hallucinations) whereas chronic exposure may be associated with abnormal dreams and other sleep disturbances, anxiety, depressed mood and suicidality. It may also be abused as a hallucinogen, especially in individuals with a history of poly-substance abuse. Recent research indicates that efavirenz directly affects monoaminergic neurotransmission and may partially substitute for psychedelic drugs, such as lysergic acid diethylamide (LSD). Efavirenz acts as a serotonin 5-HT2A receptor antagonist, a serotonin-dopamine reuptake inhibitor, an inhibitor of monoamine oxidase (MAO) and a vesicular monoamine transporter 2 (VMAT2) inhibitor, which are mechanisms common with many psychotropic drugs. Efavirenz interacts with many of the same molecular targets as the empathogen methylendioxymethamphetamine (MDMA), but the effects of the 2 drugs may differ. CONCLUSIONS: The exact mechanism of action of efavirenz as a psychotropic drug remains unclear and future studies should focus on evaluating whether prolonged exposure could lead to irreversible side effects.