Statins reduce testicular and ocular VEGF: A potential compromise to microcirculation.

Microcirculation has great importance in eye and testicular tissue and is necessary to have adequate and appropriate amount of angiogenesis. It is known that high levels of Vascular Endothelial Growth Factor (VEGF) trigger uncontrolled angiogenesis, whereas inadequate VEGF can lead to decreased tissue perfusion and oxygenation. The aim of this study was to investigate effects of VEGF in testicular and ocular tissues in both non-diabetic and diabetic rats treated by statin. Atorvastatin (10 mg/kg daily given by orally gavage) was administered for two weeks. Diabetes was induced by streptozotocin, (STZ, 45 mg/kg/ip) in diabetic group's rats. Two weeks later from STZ injection, atorvastatin treatment was initiated in diabetic group. VEGF levels were measured by using ELISA. The VEGF levels were decreased in vitrous, ocular and testicular tissues of all statin-administered rats. In diabetic group VEGF levels were found to be decreased in testicular tissue and increased in ocular tissues. CONCLUSION: Statin use decreased in VEGF levels of testicular and ocular tissues in diabetic and non-diabetic rats. Statin treatment (anti-VEGF effect) had a protective effect in the development of diabetic retinopathy, yet statins may have a negative impact on tissues that depend on microcirculation by reducing VEGF levels. Further research is needed for statins' microcellular effects.

Prevalence of atypical antipsychotic use in psychiatric outpatients: comparison of women of childbearing age with men.

To characterize current treatment practices, we compared the use of atypical antipsychotic drugs among women of childbearing age to men based on electronic medical records of 1073 hospital-based psychiatric outpatients given at least one second-generation antipsychotic drug. One quarter of psychiatric outpatients sampled were prescribed at least one atypical antipsychotic, in more than half of cases for off-label indications. Women were significantly more likely than men to be diagnosed with mood or anxiety disorders than psychotic disorders and to be prescribed quetiapine (60.7 vs. 48.0 %) or aripiprazole (31.2 vs. 23.9 %), but less likely risperidone (15.8 vs. 26.1 %) or ziprasidone (10 vs. 14 %).

Prophylaxis with antipsychotic medication reduces the risk of post-operative delirium in elderly patients: a meta-analysis.

BACKGROUND: Delirium commonly occurs in hospitalized elderly patients, resulting in increased morbidity and mortality. Although evidence for treatment of delirium exists, evidence supporting pharmacologic prevention of delirium in high risk patients is limited. OBJECTIVE: This review examined whether delirium in at-risk patients can be prevented with antipsychotic prophylaxis in the inpatient setting. DATA SOURCES: A systematic literature review of articles from January 1950 to April 2012 was conducted in PubMed, PsychInfo, and Cochrane Controlled Trials and databases. STUDY SELECTION: Five studies (1491 participants) met our inclusion criteria for analysis. Medication administered included haloperidol (three studies), risperidone (one study), and olanzapine (1 study). All five studies examined older post-surgical patients, spanning five different countries. DATA EXTRACTION: Only RCTs of antipsychotic medication used to prevent delirium were included. Key words used in the search were: "delirium," "encephalopathy," "ICU psychosis," "prevention," and "prophylaxis." Studies had to include a validated method of diagnosing delirium. Data analysis was performed using the Metan command in Stata (Stata Corp LP, College Station, TX). RESULTS: The pooled relative risk of the five studies resulted in a 50% reduction in the relative risk of delirium among those receiving antipsychotic medication compared with placebo (RR(95% CI): 0.51 (0.33-0.79; heterogeneity, p < 0.01, random effects model). Examination of the funnel plot did not indicate publication bias. CONCLUSIONS: Although few studies have examined prophylactic use of antipsychotics, this analysis suggests that perioperative use of prophylactic antipsychotics may effectively reduce the overall risk of postoperative delirium in elderly patients.

Motivations of medical students towards psychiatry: a perspective from Turkey.

Recruitment in psychiatry has been an ongoing challenge worldwide; Turkey is no exception. In this article we have reviewed the issue from multiple aspects. Negative opinions on psychiatry among medical students have been associated with various matters, such as problems with scientific soundness, stigma, prestige and financial incentives. It has been reported that these negative opinions could be reversed by clinical exposure, improved knowledge base and increased affiliation with the field. Unfortunately, reversed attitudes do not have permanency. Considering that there has not been any study focusing on recruitment problems in Turkey, we attempted to provide a perspective by reporting the results of our study conducted with Turkish medical students. Attractive qualities of psychiatry were of particular interest. We found that brain research, neuroscience, philosophy, psychotherapy and academics are main areas of interest in psychiatry. We attempt to discuss our findings in view of current literature while noting current setbacks of psychiatry residency training in Turkey. We conclude that there exists a great need for working strategies in order to improve recruitment in psychiatry, addressing the stigma and correcting false beliefs such as treatment inefficacy or compromised scientific solidity.

Empathy as a Concept from Bench to Bedside: A Translational Challenge.

Empathy is a multidimensional paradigm, and there currently is a lack of scientific consensus in its definition. In this paper, we review the possibility of compromising data during behavioral neuroscience experiments, including but not limited to those who study empathy. The experimental protocols can affect, and be affected by, empathy and related processes at multiple levels. We discuss several points to help researchers develop a successful translational pathway for behavioral research on empathy. Despite varying in their focus with no widely accepted model, current rodent models on empathy have provided sound translational explanations for many neuropsychiatric proof-of-concepts to date. Research has shown that empathy can be influenced by many parameters, some of which are to be reviewed in this paper. We emphasize the future importance of consistency in modeling proof of concept; efforts to create a multidisciplinary group which would include both bench scientists and clinicians with expertise in neuropsychiatry, and the consideration of empathy as an independent variable in animal behavioral experimental designs which is not the mainstream practice at present.

Sex difference in the progression of manic symptoms during acute hospitalization: A prospective pilot study.

OBJECTIVES: Acute mania is a serious medical condition that impacts men and women equally. Longtime presentation of manic symptoms is sex-dependent; however, little is known about acute symptoms of mania. The objective of this study is to track and compare acute manic symptoms for sex differences during inpatient hospitalization. METHODS: All patients with bipolar mania admitted to a large university hospital between January and October 2017 were invited to participate in this longitudinal naturalistic follow-up study. Manic (YMRS), depressive (MADRS), and psychotic (PAS) symptoms were tracked daily from admission to discharge. RESULTS: The total YMRS scores decreased significantly overtime (p < .0001) in both male (n = 34) and female (n = 23) patients (p = .7). However, male patients scored significantly higher in sexual interest (p = .01), disruptive and aggressive behavior (p = .01), and appearance (p < .001) while females had better insight into their illness (p = .01). Males and females received similar doses of lithium (p = .1), but males received significantly higher doses of valproic acid (VPA) in comparison with females (p = .003). However, plasma lithium and VPA concentrations at discharge were not significantly different between sexes. CONCLUSION: Our results show sex differences in the progression of certain domains of manic symptoms in a cohort of 23 female and 34 male patients admitted to a large academic center in Turkey. Males, in this sample, exhibited more sexual interest, disruptive and aggressive behaviors, better grooming, and less insight compared to females. While these results are concordant with our preclinical findings and with anecdotal clinical observations, replication in larger samples is needed.

Risk factors for valproic acid induced hyperammonemia and its association with cognitive functions.

OBJECTIVE: Valproic acid (VPA)-induced hyperammonemia (VIH), is an increase in blood ammonia levels without any alteration of hepatic enzymes, which can occur during VPA treatment. We aimed to determine the prevalence rate and the risk factors for VIH and its association with cognitive functions. METHOD: A prospective, cross-sectional study was conducted. Patients aged between 18 and 64 who were on VPA treatment and who diagnosed with mood disorders or epilepsy were enrolled in this study (n = 107). For cognitive assessment, Serial 7's and Subjective Memory Complaints Questionnaire (SMCQ) were used. Blood samples were collected for blood VPA and ammonia levels along with other laboratory tests. RESULTS: 55,3% of the sample were considered as VIH. Blood ammonia level significantly correlates with VPA blood levels, total daily dose of VPA and total number of medications concurrently used, but no significant correlation was found between blood ammonia level and cognitive test scores. Gender, body weight, blood VPA levels and the total number of medications concurrently used significantly predicted blood ammonia levels (F(4,81) = 2670, p = 0,038, R2 = 0,116). CONCLUSION: VIH is relatively high in our sample. There is a dose-dependent association between VPA and blood ammonia level. No association was found between cognitive functions and hyperammonemia however with some limitations. Future, prospective cohort studies are needed.

Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best?

Magnesium is an element of great importance functioning because of its association with many cellular physiological functions. The magnesium content of foods is gradually decreasing due to food processing, and magnesium supplementation for healthy living has become increasingly popular. However, data is very limited on the bioavailability of various magnesium preparations. The aim of this study is to investigate the bioavailability of five different magnesium compounds (magnesium sulfate, magnesium oxide, magnesium acetyl taurate, magnesium citrate, and magnesium malate) in different tissues. Following a single dose 400 mg/70 kg magnesium administration to Sprague Dawley rats, bioavailability was evaluated by examining time-dependent absorption, tissue penetration, and the effects on the behavior of the animals. Pharmacokinetically, the area under the curve calculation is highest in the magnesium malate. The magnesium acetyl taurate was found to have the second highest area under the curve calculation. Magnesium acetyl taurate was rapidly absorbed, able to pass through to the brain easily, had the highest tissue concentration level in the brain, and was found to be associated with decreased anxiety indicators. Magnesium malate levels remained high for an extended period of time in the serum. The commonly prescribed dietary supplements magnesium oxide and magnesium citrate had the lowest bioavailability when compared to our control group. More research is needed to investigate the bioavailability of magnesium malate and acetyl taurate compounds and their effects in specific tissues and on behavior.

The effects of acute foot shock stress on empathy levels in rats.

Empathy defined as the ability to understand and the share the feelings, thoughts, and attitudes of another, is an important skill in survival and reproduction. Among many factors that affect empathy include psychological stress, anxiety states. The aim of this study was to investigate the impact of acute psychological stress on empathic behavior and its association with oxytocin and vasopressin levels in amygdala and prefrontal cortex. Rats were subjected to 0.2 mA (low) and 1.6 mA (high) intensity of foot shock stress for duration of 20 min. Empathic behavior was found to be improved as a response to low intensity stress, but not to high intensity stress. As a response to lower intensity stress, vasopressin was increased in prefrontal cortex and amygdala; oxytocin was increased in only prefrontal cortex, and corticosterone levels increased in general. Anxiety indicators did not change in low intensity stress group yet; high intensity stress group demonstrated a lesser degree of anxiety response. High intensity stress group stayed unexpectedly more active in middle area of elevated plus maze test equipment, which may support impaired executive decision making abilities in the setting of high anxiety states. Further research is needed to investigate gender effects, the role of dopaminergic system and other stress related pathways in acute stress.

Acetaminophen (paracetamol) affects empathy-like behavior in rats: Dose-response relationship.

Empathy is the ability to recognize, process and respond to another's emotional state and empathic functions have been linked with a multitude of cognitive and affective processes. Impaired empathy has been linked to aggression and criminal behavior in society. Acetaminophen (paracetamol) is among the most common nonprescription (over the counter) analgesics in the world and has been already linked to reducing empathic behavior in humans. The aim of this study is to investigate the effects of acetaminophen on empathy-like behavior in Sprague Dawley rats, and we further explored the underlying mechanisms by analyzing empathy related neurohormones, e.g. oxytocin and vasopressin, in association with acetaminophen exposure in rats. Empathic behavior was assessed 30 min following acetaminophen administration (100, 200, and 400 mg/kg). The impact of single and repeated acetaminophen administrations on empathy-like behavior and anxiety level were evaluated separately. Empathy-like behavior was reduced with a single high dose of acetaminophen. Subsequent low dose administration of acetaminophen also reduced empathy-like behavior. In this study we also showed that acetaminophen decreased oxytocin and vasopressin levels in the prefrontal cortex and amygdalae. We found a negative correlation between delay in door opening time and measured prefrontal cortex oxytocin levels; we adjudged the latency in door opening time as enhanced empathic behavior which seemingly suggested the existence of a mechanism between empathy-like behavior and the prefrontal oxytocin. We observed that both a single high dose or repeated low dose administrations of acetaminophen reduced empathy-like behavior in correlation with a decrease in oxytocin and vasopressin levels in the prefrontal cortex and amygdala. Further research is needed to investigate the role of acetaminophen on the other empathic brain pathways.

Small-Town America's Despair: Infected Substance Users Needing Outpatient Parenteral Therapy and Risk Stratification.

Background  An active intravenous substance use disorder is often the primary cause of infectious diseases in this population of users and creates a barrier to successful parenteral antimicrobial management. The dilemma is compounded by dramatically limited resources in small US towns. Methods This retrospective review from January 2014 through July 2016 aimed to develop a risk stratification approach to aid rural healthcare providers in determining who among patients with addictive disorders could safely be discharged for outpatient antimicrobial therapy with a peripherally inserted central catheter (PICC). Results The high-risk group had a greater likelihood of noncompliance with antimicrobial therapy completion, as well as subsequent illicit drug use during that time frame, compared with the moderate- and low-risk groups. The low-risk group and most of the moderate-risk group could be safely discharged into the community with PICC lines. Conclusions Key in the risk stratification proposal was identifying risk behaviors and determining their degree. Such information provides pivotal delineators in developing risk stratification criteria.

The cost of a recalcitrant intravenous drug user with serial cases of endocarditis: Need for guidelines to improve the continuum of care.

We report a case of an intravenous drug user (IVDU) patient who had 4 episodes of endocarditis within a 2-year time period in rural Georgia. The institutional cost was approximately $380,000. The lack of an established transitional care plan for IVDUs to outpatient care is a common phenomenon at institutions. Guidelines are essential to optimize the quality of care rendered to IVDUs with such infections, to assist providers in utilizing limited resources, and to limit the cost to the institutions.

Exercise increases leptin levels correlated with IGF-1 in hippocampus and prefrontal cortex of adolescent male and female rats.

It is known that regular aerobic exercise has positive effects on hippocampus and prefrontal cortex. We have previously have been able to demonstrate that aerobic exercise increased IGF-1 in hippocampus. Leptin, which is associated with cognitive functions, is also involved in fat metabolism and stimulates energy consumption. While it is known that leptin stimulates IGF-1 production in hepatocytes, little known is on the link between IGF-1 and leptin in brain during aerobic exercise. In this study, we investigated the effects of regular aerobic exercise on leptin, leptin receptor expression levels in hippocampus and prefrontal cortex. Additionally, we investigated the correlation of IGF-1 levels with leptin and leptin receptor expression. During the experiment, exercise group was run on a treadmill for 30min per session at a speed of 8m/min and 0° slope, five times a week for 6 weeks. Leptin, leptin expression, IGF-1 levels and cell numbers increased in prefrontal cortex and hippocampus of exercise groups. Blood leptin levels increased in female rats in exercise group; whereas it did not change in male rats; blood IGF-1 levels were found to be increased in exercised male rats. There was a strong positive correlation between hippocampal leptin levels and hippocampal IGF-1 levels; also a strong positive correlation between hippocampal leptin receptor expression and hippocampal IGF-1. These results indicate that, increased leptin and leptin receptor expression are correlated with IGF-1 in regular aerobic exercised rats. Blood leptin and IGF-1 levels were also found to be associated with gender. Females had high blood leptin levels and males had high blood IGF-1 levels in the exercise groups.

Attenuation of ethanol withdrawal by ceftriaxone-induced upregulation of glutamate transporter EAAT2.

Alcohol withdrawal syndrome (AWS) is a potentially fatal outcome of severe alcohol dependence that presents a significant challenge to treatment. Although AWS is thought to be driven by a hyperglutamatergic brain state, benzodiazepines, which target the GABAergic system, comprise the first line of treatment for AWS. Using a rat model of ethanol withdrawal, we tested whether ceftriaxone, a ß-lactam antibiotic known to increase the expression and activity of glutamate uptake transporter EAAT2, reduces the occurrence or severity of ethanol withdrawal manifestations. After a 2-week period of habituation to ethanol in two-bottle choice, alcohol-preferring (P) and Wistar rats received ethanol (4.0 g/kg) every 6 h for 3-5 consecutive days via gavage. Rats were then deprived of ethanol for 48 h during which time they received ceftriaxone (50 or 100 mg/kg, IP) or saline twice a day starting 12 h after the last ethanol administration. Withdrawal manifestations were captured by continuous video recording and coded. The evolution of ethanol withdrawal was markedly different for P rats vs Wistar rats, with withdrawal manifestations occurring >12 h later in P rats than in Wistar rats. Ceftriaxone 100 mg/kg per injection twice per day (200 mg/kg/day) reduced or abolished all manifestations of ethanol withdrawal in both rat variants and prevented withdrawal-induced escalation of alcohol intake. Finally, ceftriaxone treatment was associated with lasting upregulation of ethanol withdrawal-induced downregulation of EAAT2 in the striatum. Our data support the role of ceftriaxone in alleviating alcohol withdrawal and open a novel pharmacologic avenue that requires clinical evaluation in patients with AWS.

Potential novel biomarkers for diabetic testicular damage in streptozotocin-induced diabetic rats: nerve growth factor Beta and vascular endothelial growth factor.

BACKGROUND: It is well known that diabetes mellitus may cause testicular damage. Vascular endothelial growth factor (VEGF) and nerve growth factor beta (NGF-ß) are important neurotrophic factors for male reproductive system. OBJECTIVE: We aimed to investigate the correlation between testicular damage and testicular VEGF and NGF-ß levels in diabetic rats. METHODS: Diabetes was induced by streptozotocin (STZ, 45 mg/kg/i.p.) in adult rats. Five weeks later testicular tissue was removed; testicular VEGF and NGF-ß levels were measured by ELISA. Testicular damage was detected by using hematoxylin and eosin staining and periodic acid-Schiff staining, and apoptosis was identified by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL). Seminiferous tubular sperm formation was evaluated using Johnsen's score. RESULTS: In diabetic rats, seminiferous tubule diameter was found to be decreased; basement membrane was found to be thickened in seminiferous tubules and degenerated germ cells. Additionally, TUNEL-positive cells were increased in number of VEGF+ cells and levels of VEGF and NGF-ß were decreased in diabetic testes. Correlation between VEGF and NGF-ß levels was strong. CONCLUSION: These results suggest that the decrease of VEGF and NGF-ß levels is associated with the increase of the apoptosis and testicular damage in diabetic rats. Testis VEGF and NGF-ß levels could be potential novel biomarkers for diabetes induced testicular damage.

Lateral hypothalamic kindling induces manic-like behavior in rats: a novel animal model.

The lateral hypothalamus integrates critical physiological functions such as the sleep-wake cycle, energy expenditure, and sexual behaviors. These functions are severely dysregulated during mania. In this study, we successfully induced manic-like behavioral phenotypes in adult, male Wistar rats through bilateral lateral hypothalamic area kindling (LHK). To test the validity of the model, we studied the effect of standard antimanic medications lithium (47.5 mg/kg) or valproic acid (200 mg/kg) twice/day for 15 days in attenuating manic-like behaviors in the LHK rat. Compared with pre-kindling behaviors, LHK rats displayed significantly increased sexual self-stimulation (P = 0.034), excessive rearing (P = 0.0005), feeding (P = 0.013), and grooming (P = 0.007) during the kindling interval. LHK rats also drank more alcohol during the mania-induction days compared with baseline ethanol consumption levels (P = 0.01). Moreover, LHK rat exhibited increased total locomotor activity (P = 0.02) with reduced rest interval (P < 0.001) during the mania induction and post-mania days compared with baseline activity levels and rest intervals. Chronic administration of lithium or valproic acid significantly attenuated manic-like behaviors in the LHK rat model. Given the behavioral phenotype and the response to standard antimanic medications, the LHK rats may provide a model for studying manic psychopathology in humans.

Positive effects of aerobic exercise on learning and memory functioning, which correlate with hippocampal IGF-1 increase in adolescent rats.

It is already known that regular aerobic exercise during adolescent period improves learning and memory in rats. In this study, we investigated the effects of regular aerobic exercise on learning, memory functioning and IGF-1 levels. IGF-1 is known to have positive effects on cognitive functions in adolescent rats. Exercise group was separated into two different groups. First half was run on a treadmill for 30 min per session at a speed of 8m/min and 0° slope, five times a week for 6 weeks. The second half was given free access to a running wheel (diameter 11.5 cm) which was connected to a digital counter and run on a treadmill for 6 weeks. Learning and memory functioning were found to be positively correlated with the exercise activity. Findings suggest increased neuron density in CA1 hippocampal region and dentate gyrus. Increased IGF-1 level was detected in hippocampus and blood serum, while IGF-1 level in liver tissue did not change with exercise activity. In conclusion, our findings indicate that learning and memory functioning were positively affected by voluntary and involuntary physical exercise which correlated increased hippocampal activity and elevated IGF-1 levels in adolescent rats.