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Objetivo: Brindar intervenciones de enfermería para el control de glucosa en la sangre. Caso clínico: Adulto joven de 49 años, irritado, con visión borrosa, muy cansado, con antecedentes de dolor en el hombro cuando hace movimientos bruscos, ya que tuvo una cirugía en el hombro años atrás, con incontinencia urinaria, también se le observa sudoración y abdomen hinchado por la presencia de gases en los intestinos, con análisis de sangre donde se pudo evidenciar que presentaba un nivel de glucosa muy alto. Métodos: El estudio es de enfoque cualitativo y de método caso único, se ejecutó en su domicilio en el mes de abril, utilizando el marco teórico de valoración de Marjory Gordon y la taxonomía NANDA-NOC-NIC. Resultados: Los resultados obtenidos quedan reflejados en taxonomía NOC, resultados con una sola escala de medición, taxonomía de intervenciones NIC dominio 1 apoyo nutricional, con un control de glucosa dentro de los valores normales, se le sugirió realizar actividad física regular, tratamiento con medicamentos e insulina. Conclusiones: En el primer diagnóstico, incontinencia urinaria de urgencia, la puntuación de cambio fue +4. En el segundo diagnóstico, motilidad gastrointestinal disfuncional, la puntuación de cambio fue +3. En el tercer diagnóstico, hipertermia, la puntuación de cambio fue +4. En el cuarto diagnóstico, riesgo de nivel de glucemia inestable, la puntuación de cambio fue +3. Finalmente, en el quinto diagnóstico, dolor agudo, la puntuación de cambio fue +1.

A major barrier to remission from an alcohol use disorder (AUD) is the continued risk of relapse during abstinence. Assessing the neuroadaptations after chronic alcohol and repeated abstinence is important to identify mechanisms that may contribute to relapse. In this study, we used a rhesus macaque model of long-term alcohol use and repeated abstinence, providing a platform to extend mechanistic findings from rodents to primates. The central amygdala (CeA) displays elevated GABA release following chronic alcohol in rodents and in abstinent male macaques, highlighting this neuroadaptation as a conserved mechanism that may underlie excessive alcohol consumption. Here, we determined circulating interleukin-1β (IL-1β) levels, CeA transcriptomic changes, and the effects of IL-1β and corticotropin releasing factor (CRF) signaling on CeA GABA transmission in male controls and abstinent drinkers. While no significant differences in peripheral IL-1β or the CeA transcriptome were observed, pathway analysis identified several canonical immune-related pathways. We addressed this potential dysregulation of CeA immune signaling in abstient drinkers with an electrophysiological approach. We found that IL-1β decreased CeA GABA release in controls while abstinent drinkers were less sensitive to IL-1β’s effects, suggesting adaptations in the neuromodulatory role of IL-1β. In contrast, CRF enhanced CeA GABA release similarly in controls and abstinent drinkers, consistent with rodent studies. Notably, CeA CRF expression was inversely correlated with intoxication, suggesting that CRF levels during abstinence may predict future intoxication. Together, our findings highlight conserved and divergent actions of chronic alcohol on neuroimmune and stress signaling on CeA GABA transmission across rodents and macaques.

Circuit manipulation has been a staple technique in neuroscience to identify how the brain functions to control complex behaviors. Chemogenetics, including designer receptors exclusively activated by designer drugs (DREADDs), have proven to be a powerful tool for the reversible modulation of discrete brain circuitry without the need for implantable devices, thereby making them especially useful in awake and unrestrained animals. This study used a DREADD approach to query the role of the nucleus accumbens (NAc) in mediating the interoceptive effects of 1.0 g/kg ethanol (i.g.) in rhesus monkeys (n = 7) using a drug discrimination procedure. After training, stereotaxic surgery was performed to introduce an AAV carrying the human muscarinic 4 receptor DREADD (hM4Di) bilaterally into the NAc. The hypothesis was that decreasing the output of the NAc by activation of hM4Di with the DREADD actuator, clozapine-n-oxide (CNO), would potentiate the discriminative stimulus effect of ethanol (i.e., a leftward shift the ethanol dose discrimination curve). The results showed individual variability shifts of the ethanol dose-response determination under DREADD activation. Characterization of the expression and function of hM4Di with MRI, immunohistochemical, and electrophysiological techniques found the selectivity of NAc transduction was proportional to behavioral effect. Specifically, the proportion of hM4Di expression restricted to the NAc was associated with the potency of the discriminative stimulus effects of ethanol. Together, these experiments highlight the NAc in mediating the interoceptive effects of ethanol, provide a framework for validation of chemogenetic tools in primates, and underscore the importance of robust within-subjects examination of DREADD expression for interpretation of behavioral findings.

Alcohol consumption is often reported to influence bone health in a dose-dependent manner where moderate alcohol intake is deemed beneficial and heavy drinking detrimental. However, this relationship may not be valid for individual alcohol consumers, as small quantities of alcohol can have detrimental skeletal effects and not all studies report clinically relevant bone loss with long-duration alcohol abuse. These discrepant findings suggest that factors beyond quantity of alcohol consumed contribute to the observed skeletal response. We propose that the interplay between intrinsic factors (e.g., age, sex, skeletal site) and extrinsic factors (e.g., age of onset of drinking, duration of drinking, comorbidities) influence the precise impact of alcohol consumption on bone health. In this review, we summarize literature reporting the effects of alcohol on the human skeleton. Based on the finding that alcohol alters the circulating levels of dozens of peptides shown to influence bone metabolism, we arrive at the conclusion that no single unifying mechanism adequately explains the diversity of reports or successfully predicts individuals most likely to be impacted favorably or unfavorably by alcohol consumption. We propose that a more holistic approach—in which drinking pattern and intrinsic factors are accounted for—is required to better understand and respond to the end-organ effects of alcohol on the skeleton.

BACKGROUND Phosphatidylethanol (PEth) homologs are ethanol metabolites used to identify and monitor alcohol drinking in humans. In this study, we measured levels of the 2 most abundant homologs, PEth 16:0/18:1 and PEth 16:0/18:2, in whole blood samples from rhesus macaque monkeys that drank ethanol daily ad libitum to assess the relationship between PEth levels and recent ethanol exposure in this animal model. METHODS Blood samples were obtained from The Monkey Alcohol Tissue Research Resource. The monkeys were first induced to consume 4% (w/v) ethanol in water from a panel attached to their home cage. Then, monkeys were allowed to drink ethanol and water ad libitum 22 h daily for 12 months and the daily amount of ethanol each monkey consumed was measured. Whole, uncoagulated blood was collected from each animal at the end of the entire experimental procedure. PEth 16:0/18:1 and PEth 16:0/18:2 levels were analyzed by HPLC with tandem mass spectrometry, and the ethanol consumed during the preceding 14 days was measured. Combined PEth was the sum of the concentrations of both homologs. RESULTS Our results show that (1) PEth accumulates in the blood of rhesus monkeys after ethanol consumption; (2) PEth homolog levels were correlated with the daily average ethanol intake during the 14-day period immediately preceding blood collection; (3) the application of established human PEth 16:0/18:1 cutoff concentrations indicative of light social or no ethanol consumption (

Development of optimal bone mass during early adulthood is determined by the balance between bone formation and resorption. The utility of minimally invasive biomarkers for monitoring bone turnover balance in maturing non-human primates has received limited attention. This study evaluated the biological variation of osteocalcin (a marker of bone formation), carboxyterminal cross-linking telopeptide of type 1 collagen (CTX, a marker of bone resorption), and the ratio of osteocalcin to CTX (reflecting bone turnover balance), in 136 rhesus and cynomolgus macaques aged 3.8–11.6 years. In a subsample of the animals (n = 28), blood samples were collected at monthly intervals over 4 months. Between-subject analysis revealed that there were no sex or species differences for CTX. Osteocalcin and the ratio of osteocalcin to CTX were higher in males than in females, and in rhesus macaques than in cynomolgus macaques. There were no changes in osteocalcin, CTX, or the ratio of osteocalcin to CTX across 4 months for any of the groups. In contrast, there was considerable within-subject variation in osteocalcin and CTX concentrations. However, differences in values exhibited no discernible pattern, suggesting that within-subject variation can be reduced by averaging repeat measurements. In summary, the data provide reference values for male and female rhesus and cynomolgus macaques and support the utility of osteocalcin and CTX as biomarkers to monitor bone turnover at the population level., Highlights • We evaluated variation in plasma osteocalcin and CTX in non-human primates. • Osteocalcin was higher in males and in rhesus than in cynomolgus macaques. • No sex or species differences were detected for CTX. • There was considerable within-subject variation in levels of osteocalcin and CTX. • Osteocalcin and CTX were stable across subjects during a 4-month time interval.

Purpose Alcohol consumption suppressed bone turnover in male non-human primates; however, it is unclear the extent to which this effect depends upon biological variables. Using archived plasma samples, we investigated whether sex, age of onset of alcohol intake, and species influence the effects of graded increases in alcohol consumption on bone turnover markers. Methods 91 male and female macaques (rhesus and cynomolgus), ranging in age from 4 years (adolescent) to 10 years (adult) were required to increase their consumption of ethanol in 30-day increments: 0 g/kg/day, followed by 0.5 g/kg/day, 1.0 g/kg/day, and, finally, 1.5 g/kg/day. Plasma osteocalcin (formation), plasma CTX (resorption) and osteocalcin to CTX ratio (turnover balance) were measured during these intervals to assess the dose-response effects of alcohol. Results We detected no relationship between dose and osteocalcin when all monkeys were combined, but there was a significant effect of sex (lower levels in females) and interactions between alcohol dose and sex (osteocalcin levels increased with dose in rhesus females). In contrast, we detected a negative linear dose-response relationship for ethanol and CTX. We did not detect a relationship between dose and osteocalcin to CTX ratio overall, but there was a significant positive relationship detected in females (no change in males). Increased age predicted lower biomarker levels for both osteocalcin and CTX. Species was a significant predictor for osteocalcin and the osteocalcin to CTX ratio in these models. Conclusion These findings indicate that age, sex, and species influence bone turnover and support the concept that factors beyond quantity of alcohol affect skeletal response to alcohol consumption., Highlights • Age, sex, and species influenced markers of bone turnover in non-human primates. • Ethanol consumption resulted in a dose-dependent reduction in CTX. • Ethanol consumption resulted in increased osteocalcin in rhesus females.

Chronic heavy drinking (CHD) of alcohol is a known risk factor for increased susceptibility to bacterial and viral infection as well as impaired wound healing. Evidence suggests that these defects are mediated by a dysregulated inflammatory response originating from myeloid cells, notably monocytes and macrophages, but the mechanisms remain poorly understood. Our ability to study CHD is impacted by the complexities of human drinking patterns and behavior as well as comorbidities and confounding risk factors for patients with alcohol use disorders. To overcome these challenges, we utilize a translational rhesus macaque model of voluntary ethanol self-administration that closely recapitulates human drinking patterns and chronicity. In this study, we examined the effects of CHD on blood monocytes and alveolar macrophages in control and CHD female macaques after 12 months of daily ethanol consumption. While monocytes from CHD female macaques generated a hyper-inflammatory response to ex vivo LPS stimulation, their response to E.Coli was dampened. In depth scRNA-Seq analysis of purified monocytes revealed significant shifts in classical monocyte subsets with accumulation of cells expressing markers of hypoxia (HIF1A) and inflammation (NFkB signaling pathway) in CHD macaques. The increased presence of monocyte subsets poised to generate a hyperinflammatory response was confirmed by the epigenetic analysis which revealed higher accessibility of promoter regions that regulate genes involved in cytokine signaling pathways. Finally, alveolar macrophages (AM) from the same animals produced higher levels of inflammatory mediators in response to LPS stimulation, but reduced ability to phagocytose bacteria. Collectively, data presented in this manuscript demonstrate that CHD primes monocytes and tissue-resident macrophages towards a more hyper-inflammatory immune response with compromised functional abilities, which could be used in diagnostic purposes or preventative measures for patients with alcohol use disorders.

The efficacy of short-term treatment with mifepristone (MIFE), a high-affinity, nonselective glucocorticoid receptor antagonist, to reduce ethanol drinking was tested in a rhesus macaque model. Stable individual daily ethanol intakes were established, ranging from 1.6 to 4.0 g/kg per day (n = 9 monkeys). After establishment of chronic ethanol intake, a MIFE dosing regimen that modeled a study of rodent drinking and human alcohol craving was evaluated. Three doses of MIFE (17, 30, and 56 mg/kg per day) were each administered for four consecutive days. Both 30 and 56 mg/kg decreased ethanol intake compared with baseline drinking levels without a change in water intake. The dose of 56 mg/kg per day of MIFE produced the largest reduction in ethanol self-administration, with the average intake at 57% of baseline intakes. Cortisol was elevated during MIFE dosing, and a mediation analysis revealed that the effect on ethanol drinking was fully mediated through cortisol. During a forced abstinence phase, access to 1.5 g/kg ethanol resulted in relapse in all drinkers and was not altered by treatment with 56 mg/kg MIFE. Overall, these results show that during active drinking MIFE is efficacious in reducing heavy alcohol intake in a monkey model, an effect that was related to MIFE-induced increase in cortisol. However, MIFE treatment did not eliminate ethanol drinking. Further, cessation of MIFE treatment resulted in a rapid return to baseline intakes, and MIFE was not effective in preventing a relapse during early abstinence. SIGNIFICANCE STATEMENT: Mifepristone reliably decreases average daily ethanol self-administration in a nonhuman primate model. This effect was mediated by cortisol, was most effective during open-access conditions, and did not prevent or reduce relapse drinking.

Hypothalamic-pituitary-adrenal (HPA) axis activity under different social settings in non-human primates is understudied.The aim of this study is to evaluate the response of pituitary-adrenal hormones (adrenocorticotropic hormone (ACTH) and cortisol) to pharmacological challenges of the HPA axis in male cynomolgus macaques under different social settings.Male cynomolgus macaques (Macaca fascicularis, n = 11) were individually (A) and socially housed (B) in alternation, over consecutive months, in an ABA design. During each experimental phase, plasma ACTH and cortisol were measured in response to low- and mild-intensity psychological stressors and following administration of saline, naloxone, ovine-corticotropin-releasing factor (oCRF), and dexamethasone.These data demonstrate that cortisol measured under low stress conditions is sensitive to social rank (dominance hierarchy) and distinguishes dominant from non-dominant animals during both individual and social settings. Administration of naloxone resulted in elevated circulating ACTH and cortisol, while oCRF only increased circulating cortisol. During social housing, the cortisol response to naloxone and oCRF was increased, whereas dexamethasone suppression of ACTH and cortisol remained consistent across all social settings.Circulating ACTH and cortisol are differentially sensitive to changes in social settings in non-human primates. Cortisol response increased during social housing and could be stimulated by both naloxone and oCRF, whereas ACTH response was generally not influenced by social setting or oCRF but was increased by naloxone. These data show differential adrenal and pituitary response to changes in social settings and a small, but consistent, effect of social dominance.

INTRODUCTION: Gestational ethanol exposure is associated with multiple developmental abnormalities, collectively termed fetal alcohol spectrum disorder (FASD). While the majority of women abstain from ethanol following knowledge of pregnancy, one contributing factor to the high FASD prevalence is that pregnancy is not detected until 4–6 weeks. Thus, ethanol consumption continues during the initial stages of fetal development. METHODS: An experimental protocol is described in which rhesus macaques self-administer 1.5 g/kg/day ethanol (or isocaloric maltose-dextrin) prior to pregnancy and through the first 60 days of a 168-day gestation term. Menstrual cycles were monitored, including measurements of circulating estradiol and progesterone levels. The latency to consume 1.5g/kg ethanol and blood ethanol concentration (BEC) were measured. RESULTS: Twenty-eight fetuses (14 ethanol, 14 controls) were generated in this study. Ethanol did not affect menstrual cycles, or the probability of successful breeding. No ethanol-induced gross adverse effects on pregnancy were observed. Individual variability in latency to complete drinking translated into variability in BEC, measured 90 minutes following session start. Drinking latencies in controls and ethanol-drinkers were longer in the second gestational month than in the first. All pregnancies reached the planned experimental time point of G85, G110, or G135, when in utero MRIs were performed, fetuses were delivered by cesarean section, and brains were evaluated with ex vivo procedures, including slice electrophysiology. Fetal tissues have been deposited to the Monkey Alcohol Tissue Research Resource (MATRR). CONCLUSION: This FASD model takes advantage of the similarities between humans and rhesus macaques in gestational length relative to brain development, as well as similarities in ethanol self-administration and metabolism. The daily 1.5 g/kg dose of ethanol through the first trimester does not influence pregnancy success rates. However, pregnancy influences drinking behavior during the second month of pregnancy. Future publications using this model will describe the effect of early-gestational ethanol exposure on anatomical and functional brain development at subsequent gestational ages.

Alcohol use disorder is a significant global burden. Stress has been identified as an etiological factor in the initiation and continuation of ethanol consumption. Understanding adaptations within stress circuitry is an important step toward novel treatment strategies. The effects of protracted abstinence following long-term ethanol self-administration on the central nucleus of the amygdala (CeA) and the hypothalamic paraventricular nucleus (PVN) were evaluated in male rhesus monkeys. Using whole-cell patch-clamp electrophysiology, inhibitory GABAergic transmission in the CeA and excitatory glutamatergic transmission in the PVN were measured. CeA neurons from abstinent drinkers displayed an elevated baseline spontaneous inhibitory postsynaptic current (sIPSC) frequency compared with controls, indicating increased presynaptic GABA release. Application of acute ethanol significantly increased the frequency of sIPSCs in controls, but not in abstinent drinkers, suggesting a tolerance to ethanol-enhanced GABA release in abstinent rhesus monkeys with a history of chronic ethanol self-administration and repeated abstinence. In the PVN, the frequency of spontaneous excitatory postsynaptic currents (sEPSC) was elevated in abstinent drinkers compared with controls, indicating increased presynaptic glutamate release. Notably, acute ethanol decreased presynaptic glutamate release onto parvocellular PVN neurons in both controls and abstinent drinkers, suggesting a lack of tolerance to acute ethanol among PVN neurons. These results are the first to demonstrate distinct synaptic adaptations and ethanol sensitivity in both the extrahypothalamic and hypothalamic stress circuits in abstinent rhesus males. Importantly, our findings describe adaptations in stress circuitry present in the brain at a state during abstinence, just prior to relapse to ethanol drinking.

BACKGROUND: Recent work with long-term ethanol self-administration in non-human primate models has revealed a complex array of behavioral and physiological effects that closely mimic human alcohol abuse. Detailed neurophysiological analysis in these models suggests a myriad of pre- and postsynaptic neurobiological effects that may contribute to the behavioral manifestations of long-term ethanol drinking. The molecular mechanisms regulating presynaptic effects of this chronic ethanol exposure are largely unknown. To this end, we analyzed the effects of long-term ethanol self-administration on the levels of presynaptic SNARE complex proteins in Mucacca mullatta basolateral amygdala, a brain region known to regulate both aversive and reward-seeking behaviors. METHODS: Basolateral amygdala samples from control and ethanol-drinking male and female monkeys were processed. Total basolateral amygdala protein was analyzed by Western blotting using antibodies directed against both core-SNARE and SNARE-associated proteins. We also performed correlational analyses between protein expression levels and a number of ethanol drinking parameters, including life-time grams of ethanol consumed, preference, and blood ethanol concentration. RESULTS: Significant interactions or main effects of sex/drinking were seen for a number of SNARE core and SNARE-associated proteins. Across the range of ethanol drinking phenotypes, SNAP25 and Munc13-1 proteins levels were significantly different between males and females; and Munc13-2 levels were significantly lower in animals with a history of ethanol drinking. A separate analysis of very-heavy drinking individuals revealed significant decreases in Rab3c (females) and Complexin 2 (males). CONCLUSIONS: Protein expression analysis of basolateral amygdala total protein from controls and animals following long-term ethanol self-administration suggest a number of alterations in core SNARE or SNARE-associated components that could dramatically alter presynaptic function. A number of proteins or multi-protein components were also correlated with ethanol drinking behavior, which suggest a potentially heritable role for presynaptic SNARE proteins.

Aldosterone regulates electrolyte and fluid homeostasis through binding to the mineralocorticoid receptors (MRs). Previous work provides evidence for a role of aldosterone in alcohol use disorders (AUDs). We tested the hypothesis that high functional activity of the mineralocorticoid endocrine pathway contributes to vulnerability for AUDs. In Study 1, we investigated the relationship between plasma aldosterone levels, ethanol self-administration and the expression of CYP11B2 and MR (NR3C2) genes in the prefrontal cortex area (PFC) and central nucleus of the amygdala (CeA) in monkeys. Aldosterone significantly increased after 6- and 12-month ethanol self-administration. NR3C2 expression in the CeA was negatively correlated to average ethanol intake during the 12 months. In Study 2, we measured Nr3c2 mRNA levels in the PFC and CeA of dependent and nondependent rats and the correlates with ethanol drinking during acute withdrawal. Low Nr3c2 expression levels in the CeA were significantly associated with increased anxiety-like behavior and compulsive-like drinking in dependent rats. In Study 3, the relationship between plasma aldosterone levels, alcohol drinking and craving was investigated in alcohol-dependent patients. Non-abstinent patients had significantly higher aldosterone levels than abstinent patients. Aldosterone levels positively correlated with the number of drinks consumed, craving and anxiety scores. These findings support a relationship between ethanol drinking and the aldosterone/MR pathway in three different species. Funding Agencies|European Foundation for Alcohol Research (ERAB) [EA0619]; ERAB exchange award [EXA0802]; National Institutes of Health (NIH) [ZIA-AA000218]; Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism (NIAAA); Intramural Research Program of the National Institute on Drug Abuse (NIDA); National Institute of Mental Health [MH101076]; Swedish Research Council; Pearson Center for Alcoholism and Addiction Research; NIAAA [AA023867, AA010760, AA08459, AA109431]

The use of non-human primates (NHPs) in studies of volitional, oral self-administration of alcohol can help address the complex interplay between stress and excessive alcohol consumption. There are aspects to brain, endocrine and behavior of NHPs, particularly macaques, that provide a critical translational link towards understanding the risks and consequences of alcohol use disorders (AUDs) in humans. These include wide individual differences in escalating daily alcohol intake, accurate measures of hypothalamic-pituitary-adrenal (HPA) axis hormonal interactions, neuroanatomical specificity of synaptic adaptations to chronic alcohol, genetic similarities to humans, and the ability to conduct in vivo brain imaging. When placed in a framework that alcohol addiction is a sequence of dysregulations in motivational circuitry associated with severity of AUD, the NHP can provide within-subject information on both risks for and consequences of repeatedly drinking to intoxication. Notably, long-term adaptations in neurocircuitry that mediate behavioral reinforcement, stress responses and executive functions are possible with NHPs. We review here the substantial progress made using NHPs to address the complex relationship between alcohol and stress as risk factors and consequences of daily drinking to intoxication. This review also highlights areas where future studies of brain and HPA axis adaptations are needed to better understand the mechanisms involved in stress leading to excessive alcohol consumption. This article is part of the Special Issue entitled “Alcoholism”.

Acute ethanol activates the hypothalamic–pituitary–adrenal (HPA) axis, while long-term exposure results in a blunted neuroendocrine state, particularly with regards to the primary endpoint, cortisol, the primary glucocorticoid produced in the adrenal cortex. However, it is unknown if this dampened neuroendocrine status also influences other adrenocortical steroids. Plasma concentration of the mineralocorticoid and neuroactive steroid precursor deoxycorticosterone (DOC) is altered by pharmacological challenges of the HPA axis in cynomolgus monkeys. The present study investigated HPA axis regulation of circulating DOC concentration over the course of ethanol (4% w/v) induction and self-administration in non-human primates (Macaca fasciculata, n = 10). Plasma DOC, measured by radioimmunoassay, was compared at baseline (ethanol naïve), during schedule-induced polydipsia, and following 6-months of 22 h/day access to ethanol and water. The schedule induction of ethanol drinking did not alter basal DOC levels but selectively dampened the DOC response to pharmacological challenges aimed at the anterior pituitary (ovine corticotrophin-releasing hormone) and adrenal gland (post-dexamethasone adrenocorticotropin hormone), while pharmacological inhibition of central opioid receptors with naloxone greatly enhanced the DOC response during induction. Following 6 months of ethanol self-administration, basal DOC levels were increased more than twofold, while responses to each of the challenges normalized somewhat but remained significantly different than baseline. These data show that HPA axis modulation of the neuroactive steroid precursor DOC is markedly altered by the schedule induction of ethanol drinking and long-term voluntary ethanol self-administration. The consequences of chronic ethanol consumption on HPA axis regulation of DOC point toward allostatic modification of hypothalamic and adrenal function.

This article on implementing a machine vision process, such as to enable support processes of agriculture. Work is born of the problems presented by different crops, causing great losses in both time and costs. Using machine vision every inconvenience that occurs from the stage of germination and growth to the maturation phase of each culture was analyzed. To this end, different methods of image processing such as segmentation, feature extraction and pattern recognition were used. Finally the results of image processing is achieved evidence which affects the culture, whether pests or weeds who are altering a given area of cultivation, and so have an early detection of the disease to prevent it from spreading to all cultivation.

Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are not fully understood. Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Female rhesus macaques completed 1 year of daily (22 h/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa opioid receptor agonist) induced inhibition of dopamine release. Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa opioid receptors, which both act as negative regulators of presynaptic dopamine release, was moderately and robustly enhanced in ethanol drinkers. Greater uptake rates and sensitivity to D2-type autoreceptor and kappa opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system and suggest that the dopamine and dynorphin/kappa opioid receptor systems may be efficacious pharmacotherapeutic targets in the treatment of alcohol use disorders.

A bidirectional relationship between stress and ethanol exists whereby stressful events are comorbid with problematic ethanol use and prolonged ethanol exposure results in adaptations of the physiological stress response. Endocrine response to stress is initiated in the hypothalamic paraventricular nucleus (PVN) with the synthesis and release of corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP). Alterations in CRH and AVP following long-term ethanol exposure in rodents is well demonstrated, however little is known about the response to ethanol in primates or the mechanisms of adaptation. We hypothesized that long-term ethanol self-administration in nonhuman primates would lead to ultrastructural changes in the PVN underlying adaptation to chronic ethanol. Double-label immunogold electron microscopy (EM) was used to measure presynaptic gamma-aminobutyric acid (GABA) and glutamate density within synaptic terminals contacting CRH- and AVP-immunoreactive dendrites. Additionally, pituitary-adrenal hormones (ACTH, cortisol, DHEA-s and aldosterone) under two conditions (low and mild stress) were compared before and after self-administration. All hormones were elevated in response to the mild stressor independent of ethanol consumption. The presynaptic glutamate density in recurrent (i.e., intra-hypothalamic) CRH terminals was highly related to ethanol intake, and may be a permissive factor in increased drinking due to stress. Conversely, glutamate density within recurrent AVP terminals showed a trend-level increase following ethanol, but was not related to average daily consumption. Glutamate density in non-recurrent AVP terminals was related to aldosterone under the low stress condition while GABAergic density in this terminal population was related to water consumption. The results reveal distinct populations of presynaptic terminals whose glutamatergic or GABAergic density were uniquely related to water and ethanol consumption and circulating hormones.