Evaluation of immunogenicity and reactogenicity of COVID-19 vaccines in pregnant women.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with increased risk of adverse maternal and perinatal outcomes. Vaccines are highly effective at preventing severe coronavirus disease 2019 (COVID-19), but there are limited data on COVID-19 vaccines in pregnancy. This study aimed to investigate the reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women when administered according to the 12-week-interval dosing schedule recommended in the UK. METHODS: This was a cohort study of pregnant women receiving COVID-19 vaccination between April and September 2021. The outcomes were immunogenicity and reactogenicity after COVID-19 vaccination. Pregnant women were recruited by phone, e-mail and/or text and were vaccinated according to vaccine availability at their local vaccination center. For immunogenicity assessment, blood samples were taken at specific timepoints after each dose to evaluate nucleocapsid protein (N) and spike protein (S) antibody titers. The comparator group comprised non-pregnant female healthcare workers in the same age group who were vaccinated as part of the national immunization program in a contemporaneous longitudinal cohort study. Longitudinal changes in serum antibody titers and association with pregnancy status were assessed using a two-step regression approach. Reactogenicity assessment in pregnant women was undertaken using an online questionnaire. The comparator group comprised non-pregnant women aged 18-49 years who had received two vaccine doses in primary care. The association of pregnancy status with reactogenicity was assessed using logistic regression analysis. RESULTS: Overall, 67 pregnant women, of whom 66 had received a mRNA vaccine, and 79 non-pregnant women, of whom 50 had received a mRNA vaccine, were included in the immunogenicity study. Most (61.2%) pregnant women received their first vaccine dose in the third trimester, while 3.0% received it in the first trimester and 35.8% in the second trimester. SARS-CoV-2 S-antibody geometric mean concentrations after mRNA vaccination were not significantly different at 2-6 weeks after the first dose but were significantly lower at 2-6 weeks after the second dose in infection-naïve pregnant compared with non-pregnant women. In pregnant women, prior infection was associated with higher antibody levels at 2-6 weeks after the second vaccine dose. Reactogenicity analysis included 108 pregnant women and 116 non-pregnant women. After the first dose, tiredness and chills were reported less commonly in pregnant compared with non-pregnant women (P = 0.043 and P = 0.029, respectively). After the second dose, feeling generally unwell was reported less commonly (P = 0.046) in pregnant compared with non-pregnant women. CONCLUSIONS: Using an extended 12-week interval between vaccine doses, antibody responses after two doses of mRNA COVID-19 vaccine were found to be lower in pregnant compared with non-pregnant women. Strong antibody responses were achieved after one dose in previously infected women, regardless of pregnancy status. Pregnant women reported fewer adverse events after both the first and second dose of vaccine. These findings should now be addressed in larger controlled studies. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Comparison of the Efficacy of Different Concentrations of Diclofenac Sodium Phonophoresis (1.16% vs 2.32%) in Patients with Knee Osteoarthritis: a Randomized Double-Blind Controlled Trial.

PURPOSE OF THE STUDY The objective of the present study is to compare the efficacy of two different concentrations of diclofenac sodium phonophoresis (DSPH) (1.16% vs 2.32%) in patients with knee osteoarthritis (OA). MATERIAL AND METHODS A randomized, double-blind, controlled design was applied. Ninety patients (mean age± SD, 59.98 ± 8.89 years) who had Kellgren-Lawrence (K-L) grades II to III knee OA were randomly allocated into three groups; 1.16% DSPH, 2.32% DSPH, TUS (30 in each group). Each patient was treated five sessions per week for two weeks. A 100-mm visual analogue scale (VAS) for usual pain and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were evaluated before and after treatment in all groups. RESULTS The VAS pain and WOMAC scores were significantly improved after treatment in all groups (p < 0.05). The 2.32% DSPH showed more significant effects than the 1.16% DSPH, both in improving WOMAC- pain and physical function scores (p = 0.020, p = 0.008) and reducing the VAS pain measure, although it did not reach the level of significance (p = 0.077). The 2.32% DSPH was superior to the TUS, both in reducing the VAS pain measure (p < 0.001) and in improving WOMAC-pain, stiffness, physical function and total scores (p = 0.022, p = 0.016, p < 0.001, p < 0.001 respectively). 1.16% DSPH significantly reduced stiffness and physical function scores compared with TUS (p = 0.042, p = 0.047). CONCLUSIONS DSPH and TUS are effective treatments for knee OA. Our results indicated that 2.32% DSPH produces additional benefits to functional improvement and pain reduction compared with 1.16% DSPH in K-L grades II to III knee OA. Key words: diclofenac sodium, knee osteoarthritis, phonophoresis, therapeutic ultrasound, topical formulation.

Intrathecal Autologous Bone Marrow-Derived Hematopoietic Stem Cell Therapy in Neurological Diseases.

BACKGROUND: Cellular transplantation is a promising treatment strategy for neurological diseases. OBJECTIVE: To report the results of intrathecal hematopoietic stem cell therapy in different neurological diseases in the past 6 years in a single center. METHODS: From October 2011 to September 2018, 220 patients with various neurological diseases were transplanted intrathecally by their bone marrow stem cells. To have a longer follow up, we only reported the first 80 patients, transplanted up to July 2015-10 patients had spinal cord injuries and paralysis, 12 had advanced Parkinson's disease, 28 had cerebral palsy, 7 had hypoxic brain damage, 2 had autism, 4 had multiple sclerosis, 5 had progressive cerebellar atrophy, and 12 had other neurological diseases. The patients were admitted to the Bone Marrow Transplant Unit. On the first day, 50-200 (median 100) mL bone marrow was aspirated from the patients' posterior iliac crests, mixed with 120 mL culture media (RPMI), and 12 mL heparin. The samples were then transferred to immunology lab in cold box. Mononuclear cells (MNCs) were separated by a Ficoll-Hypaque gradient, washed, and suspended in ringers. Cell viability was assessed with trypan blue viability test. Transplantation was performed 3-4 hours after bone marrow collection. 5-10 mL of the cerebrospinal fluids were aspirated and about 20 mL MNCs (containing stem cells) in ringers were injected intrathecally (IT). The patients were laid down on their back for 4-5 hours. The median number of MNCs was 4×107 (range 1-450×107). The median viability of the cells was 90% (range 60%-98%). The patients received intravenous ceftriaxone every 12 hours and were discharged from the hospital few days after autologous stem cell therapy. RESULTS: We noted clinical improvements in 9 of 12 patients with Parkinson's disease, 20 of 28 patients with cerebral palsy, 6 of 7 patients with hypoxic brain damage, 2 of 4 patients with multiple sclerosis, and 4 of 5 patients with cerebellar atrophy. The improvements were noted after 2-4 weeks of cell therapy. There were no improvements in patients with spinal cord injury and complete paralysis and those with autism. There were variable improvements in other patients treated. CONCLUSION: Most patients with advanced Parkinson's disease, cerebral palsy, hypoxic brain damage, progressive cerebellar atrophy, and kernicterus neuropathy reported clinical effects of this safe intervention resulting in better functioning and an increased quality of life.

Long-term characterization of the Flinders Sensitive Line rodent model of human depression: Behavioral and PET evidence of a dysfunctional entorhinal cortex.

The etiology of depression is unknown but has been associated with dysregulation of neuronal activity at numerous loci on the limbic-cortical circuitry. The Flinders Sensitive Line (FSL) is a validated rodent model of human depression with spontaneously emerging behavioral and physiological phenotype, however, the durability and robustness of the phenotypes have not been described. The objective of the current study was to evaluate longitudinal dynamics of the depressive-like symptoms in this animal model. FSL and control rats of both genders were assessed over 8 months, characterizing their performance at different time points on motor, sensorimotor and complex learning/memory based tasks. Changes over time in physiological parameters, such as corticosterone and blood glucose levels, were monitored. Regional glucose metabolism, used as a marker of neuronal activity, was assessed at different time points using F18-FDG Positron Emission Tomography (PET). Results show that certain deficits at 2-3 months--on tests such as the Elevated Plus Maze, Object Recognition, and the Forced Swim Test--were transitory and the phenotype was no longer present when re-testing at 6-7 months of age. However, a stable impairment was detected on a learning and memory task, particularly indicating dysfunction in retention of spatial information. Furthermore, at multiple time points, the PET scan indicated a significate bilateral, hypo-metabolism in the temporal lobes in the FSL rats compared to healthy controls. The data suggests possible alterations of entorhinal cortex metabolism concomitant with specific behavioral changes and supports the importance of understanding the dynamics and the time and gender dependence of the phenotypes present.

Allogeneic hematopoietic cell transplantation after failed autologous transplant for lymphoma using TLI and anti-thymocyte globulin conditioning.

We describe 47 patients with lymphoma and failed prior autologous hematopoietic cell transplantation (HCT) who received TLI-ATG (anti-thymocyte globulin) conditioning followed by allogeneic HCT. Thirty-two patients had non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma (n=19), T-cell NHL (n=6), mantle cell lymphoma (n=4) or other B-cell subtypes (n=3)), and 15 had Hodgkin lymphoma. The median follow-up was 4.9 (range, 2.1-11.9) years. The cumulative incidence of grade II-IV acute GvHD at day +100 was 12%, and the cumulative incidence of extensive chronic GvHD at 1 year was 36%. The 3-year cumulative incidences of overall survival (OS), PFS and non-relapse mortality (NRM) were 81%, 44% and 7%, respectively. Fifteen patients died (relapse, n=10; NRM, n=5). Among the 25 patients with relapse after allogeneic HCT, 11 (44%) achieved durable (>1 year) CRs following donor lymphocyte infusion or chemoradiotherapy. The majority of surviving patients (75%; n=24) were able to discontinue all immunosuppression. For patients with relapsed lymphoma after autologous HCT, allogeneic HCT using TLI-ATG conditioning is a well-tolerated, predominantly outpatient therapy with low NRM (7% at 3 years), a low incidence of GvHD, durable disease control and excellent OS (81% at 3 years).

Workaholism: are physicians at risk?

BACKGROUND: Work addiction (WA), often called 'workaholism', is a relatively recent concept that has not yet been clearly defined. Ongoing studies have found prevalence rates that are highly variable due to the diversity of the models used and the populations studied. AIMS: To assess the characteristics of WA among hospital medical staff. METHODS: All physicians practising at a French university hospital were invited to participate in a survey based on two questionnaires: the Work Addiction Risk Test (WART) for WA and the Job Contents Questionnaire (JCQ) to assess psychosocial constraints at work. RESULTS: There were 444 responding physicians. The response rate was 45%. Thirteen per cent of respondents were considered to be highly work addicted and a further 35% were considered mildly work addicted. Professors had the highest average WART score, but neither age nor sex was associated with WA. Furthermore, all 3D scores obtained using the JCQ correlated with the WART score; the highest correlation coefficient being obtained between the WART score and the job demands score, indicating that workaholics experienced high job demands. CONCLUSIONS: WA especially affects professors, who have the highest status amongst doctors in the hospital hierarchy. This study highlights the importance of constraints and workload, which are consistent with individual vulnerability factors. These factors may help identify ways of preventing and managing this type of addiction, through improvement of working conditions and organizational structures.

Human Bone Marrow-derived Mesenchymal Stem Cell: A Source for Cell-Based Therapy.

BACKGROUND: The ability of mesenchymal stem cells (MSCs) to differentiate into many cell types, and modulate immune responses, makes them an attractive therapeutic tool for cell transplantation and tissue engineering. OBJECTIVE: This project was designed for isolation, culture, and characterization of human marrow-derived MSCs based on the immunophenotypic markers and the differentiation potential. METHODS: Bone marrow of healthy donors was aspirated from the iliac crest. Mononuclear cells were layered over the Ficoll-Paque density-gradient and plated in tissue cultures dish. The adherent cells expanded rapidly and maintained with periodic passages until a relatively homogeneous population was established. The identification of adherent cells and the immune-surface markers was performed by flow cytometric analysis at the third passage. The in vitro differentiation of MSCs into osteoblast and adipocytes was also achieved. RESULTS: The MSCs were CD11b (CR3), CD45, CD34, CD31 (PCAM-1), CD40, CD80 (B7-1), and HLA-class II negative because antigen expression was less than 5%, while they showed a high expression of CD90, and CD73. The differentiation of osteoblasts, is determined by deposition of a mineralized extracellular matrix in the culture plates that can be detected with Alizarin Red. Adipocytes were easily identified by their morphology and staining with Oil Red. CONCLUSION: MSCs can be isolated and expanded from most healthy donors, providing for a source of cell-based therapy.

Cross-education of muscle strength: cross-training effects are not confined to untrained contralateral homologous muscle.

The aim of this study was to evaluate whether electrical muscle stimulation (EMS) on dominant wrist flexors causes an increase in the muscle strength of the contralateral wrist extensors. Twenty-three healthy, young, adult men were included in this prospective, double-blind, controlled study. Participants were randomly allocated to the EMS group or Control group. Electrodes were placed over the flexor aspect of the right forearm in both groups. In the EMS group, passive wrist extension and (EMS) that caused powerful muscle contraction were simultaneously applied. In the Control group, a conventional mode of transcutaneous electrical nerve stimulation was applied without causing any contraction. A group effect (P=0.0001) and group-by-time interaction were found (P=0.0001) for both the wrist flexor and extensor muscles, but not group-by-time-by-arm interactions. This implies that the effect of the interventions was similar in both arms, but that the response was significantly larger in the EMS than in the Control group. The results of the current study suggest that cross-education is not confined to the untrained contralateral wrist flexors and that the strength increase may also be observed in the contralateral wrist extensors.

Neonatal 6-hydroxydopamine lesions of the frontal cortex in rats: persisting effects on locomotor activity, learning and nicotine self-administration.

Dopaminergic innervation of the frontal cortex in adults is important for a variety of cognitive functions and behavioral control. However, the role of frontal cortical dopaminergic innervation for neurobehavioral development has received little attention. In the current study, rats were given dopaminergic lesions in the frontal cortex with local micro-infusions of 6-hydroxydopamine (6-OHDA) at 1 week of age. The long-term behavioral effects of neonatal frontal cortical 6-OHDA lesions were assessed in a series of tests of locomotor activity, spatial learning and memory, and i.v. nicotine self-administration. In addition, neurochemical indices were assessed with tissue homogenization and HPLC in the frontal cortex, striatum, and nucleus accumbens of neonatal and adult rats after neonatal 6-OHDA lesions. In neonatal rats, frontal 6-OHDA lesions as intended caused a significant reduction in frontal cortical dopamine without effects on frontal cortical 5-HT and norepinephrine. The frontal cortical dopamine depletion increased 5-HT and norepinephrine levels in the nucleus accumbens. Locomotor activity assessment during adulthood in the figure-8 maze showed that lesioned male rats were hyperactive relative to sham-lesioned males. Locomotor activity of female rats was not significantly affected by the neonatal frontal 6-OHDA lesion. Learning and memory in the radial-arm maze was also affected by neonatal frontal 6-OHDA lesions. There was a general trend toward impaired performance in early maze acquisition and a paradoxical improvement at the end of cognitive testing. Nicotine self-administration showed significant lesion x sex interactions. The sex difference in nicotine self-administration with females self-administering significantly more nicotine than males was reversed by neonatal 6-OHDA frontal cortical lesions. Neurochemical studies in adult rats showed that frontal cortical dopamine and DOPAC levels significantly correlated with nicotine self-administration in the 6-OHDA-lesioned animals but not in the controls. Frontal cortical 5-HT and 5HIAA showed inverse correlations with nicotine self-administration in the 6-OHDA-lesioned animals but not in the controls. These results show that interfering with normal dopamine innervation of the frontal cortex during early postnatal development has persisting behavioral effects, which are sex-specific.

Epidemiology of orofacial herpes simplex virus infections in the general population in France: results of the HERPIMAX study.

BACKGROUND: Prevalence of clinically manifest orofacial herpes in the general population is poorly characterized. Objectives To establish the lifetime prevalence of clinically manifest orofacial herpes and its relationship with herpes simplex virus (HSV) serotype in the French general population. PATIENTS/METHODS: Subjects (N = 2796) were serotyped for HSV1 and HSV2 and provided data on herpetic symptoms by questionnaire. Subjects reporting at least one episode of orobuccal ulcerative mucosal lesions were classified as clinically manifest orofacial herpes. RESULTS: Lifetime prevalence of clinically manifest orofacial herpes was 38.3% (42.1% in women, 32.4% in men). Prevalence in subjects seropositive for HSV1 was 50.3%. This prevalence rate was independent of HSV2 serotype. Prevalence in subjects infected with HSV2 alone was similar to that in subjects seronegative for HSV. LIMITATIONS: Lack of case ascertainment limits precision of the data. CONCLUSIONS: Clinically manifest orofacial herpes was reported in one third of the sample, principally associated with HSV1 infection. HSV2 infection did not produce orofacial lesions nor influence clinical manifestations of HSV1 infection.

Demographic parameters of wrinkling aphid of pistachio leaf, Forda hirsuta Mordv. (Hem.:Pemphigidae) insitu of Rafsanjan's orchards.

Wrinkling aphid of pistachio leaf, Forda hirsuta Mordv. (Hem.:Pemphigidae) is one of the pests of pistachio trees. This aphid caused the shrinkage, thickening, and changing the color of the pistachio leaves. Since insect feeds from leave edges, the thick and rolled upward wrinkles were formed, which its green color turned into red. Therefore, its economical damages are out of direct feeding from plant extraction, twisting pistachio leaves, and the decrease of photosynthesis. In this research two orchards and 10 trees that each of them were selected in Rafsanjan region and 58 fundatrix galls, 120 nymphal galls were marked and the demographic parameters for apterus parthenogenesis female of this aphid were calculated via daily observations. The results indicated that intrinsic rates of increase (r) for 1, 2 and 3 generations were 0.01, 0.0638 and 0.0575 femal/femal/days respectively, Doubling time (DT) were 69.31, 10.52 and 12.04 days, respectively, net fecundity rates were 1.71, 11.5 and 7.37 femal/femal/days, respectively, Net fertility rates were 1.11, 8.87 and 5.01 days, respectively, and mean generation times (Tc) were calculated to be 31.5, 32.2 and 31.87 days, respectively. Other reproductive parameters such as gross hatch rate, gross fecundity rate, gross fertility rate, mean age gross fecundity and fertility, mean age net fecundity and fertility, mean age hatch, finite rate of increase (lambda), intrinsic birth rate (b) intrinsic death rate (d) and daily reproductive rate were also calculated. The results revealed that population parameters especially r in the first and second generations were lowest and highest, respectively and mean longevity of fundatrix was 30 days and the born nymphs made separate galls in the edge of pistachio leaves.

[Five-year survival of Ile-de-France cancer patients diagnosed in 1994]. / Survie à cinq ans des patients ayant eu un diagnostic de cancer en 1994 en Ile-de-France.

BACKGROUND: This study aimed to estimate survival at 5 years by localization, sex and stage of the patients who presented a new cancer in 1994 in the Ile-de-France area. METHODS: A cohort study began in 1994 by an exhaustive collection of the incidental cancers notified in the Ile-de-France area at the health insurance (27,080 patients). A stratified random sample based on tumor localization was followed at 1 year, 3 years and 5 years. The analysis of the observed survival was carried out according to Kaplan-Meier method. Relative survival was calculated according to Ederer II method. RESULTS: The follow-up sample concerned 4,166 patients. For all cancers, relative survival at 5 years was 65% for the women and 51% for the men. Relative survival rate at 5 years was 82% for the women with a breast cancer (98% for the patients in stage I) and 66% for those with a cancer of the cervix. Relative survival at 5 years for colonic cancer was 67% for men and 54% for women. For lung cancer, the relative survival rate fell from 47% for patients in stage I to 5% for those in stage IV. CONCLUSION: Our study produces population-based survival data for a entire geographical area covering 20% of the French population. Survival improves with earlier diagnosis but depends also on quality of care and availability of care: access to medical care can be a favouring factor. While in terms of incidence the situation in the Ile-de-France area is close to the national situation, survival at 5 years for a set of tumors appears to be better in this area than the nationwide figures. Besides providing information useful to determine mortality and incidence, the health insurance data offer additional insight to cancer epidemiology and contribute to better knowledge of this disease.

Oxytocin promotes spermiation and sperm transfer in the mouse.

Spermatogenesis is a complex process during which developing germ cells move from the base of the seminiferous tubule towards the lumen where they are shed. Studies in the rat suggest that seminiferous tubule contraction, induced by exogenous oxytocin, promotes spermiation. This study examines the role of testicular oxytocin in development of the testes, spermatogenesis and spermiation in the mouse. Groups of wild-type (WT) mice, oxytocin knockout mice (OTKO) deficient in testicular oxytocin and mice containing an oxytocin transgene (bOT4.2) that over express testicular oxytocin were killed between days 5 and 45 post partum. The testes and epididymides were removed weighed and prepared either for histological and morphometric study by light microscopy, for sperm counts (epididymis), or extracted for determination of oxytocin content (testis - day 45 only). Testicular oxytocin concentrations were significantly greater (p < 0.05) in bOT4.2 mice than in WT or OTKO mice. No differences in testicular and epididymal weight, or in diameter and area of seminiferous tubules between the mice genotypes were found at any given time. Germ cell development was similar in all genotypes and was comparable with previous studies. The timing of spermiation between the groups was significantly different (p < 0.001) with bOT4.2 < WT < OTKO and the appearance of epididymal sperm was significantly different (p < 0.05) with bOT4.2 < WT < OTKO. There were significant correlations between the percentage of tubules containing residual bodies and epididymal sperm count (p < 0.05) and between the percentage of animals containing residual bodies and the percentage of animals containing epididymal sperm (p < 0.01). These data suggest that in the mouse oxytocin, whilst not involved in germ cell development, is important in the process of spermiation and sperm transfer in the mouse.

Nicotinic treatment for cognitive dysfunction.

Nicotinic medications may provide beneficial therapeutic treatment for cognitive dysfunction such as Alzheimer's disease, schizophrenia and attention deficit hyperactivity disorder (ADHD). For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer's disease, schizophrenia or ADHD as well as normal nonsmoking adults. To follow-up on this proof of principal that nicotinic treatment of cognitive dysfunction holds promise, it is important to use animal models to determine the critical neurobehavioral bases for nicotinic involvement in cognitive function so that more selective nicotinic analogues that improve cognitive function with fewer side effects can be developed. We have found with local infusion in rat studies that the hippocampus and amygdala are important substrates for nicotinic effects on working memory function. Both alpha7 and alpha4beta2 nicotinic receptors are involved in working memory. Nicotinic interactions with dopaminergic and glutaminergic systems are also important in the basis of cognitive function. Studies of the neural nicotinic mechanisms underlying cognitive function are key for opening avenues for development of safe and effective nicotinic treatments for cognitive dysfunction.

Genetic selection of rats with high and low body temperatures.

Body (core) temperature (T(c)) directly affects all biological processes, including sensitivity to toxic chemicals, development, aging, and drug metabolism. To understand how T(c) affects these processes it is necessary to alter T(c) independently of other physiological processes. The purpose of this study was to determine whether selective breeding techniques can be used to develop lines of rats with hyperthermic and hypothermic T(c)'s. T(c) and motor activity of 24 female and 23 male rats (parental line) of the NIH heterogenous stock were monitored by telemetry for 96h at a T(a) of 22 degrees C. The mean 24h T(c) of the male and female rats was 37.3 degrees C with a range of 37-38.2 degrees C. T(c) was not correlated with motor activity or body weight. Pairs with the lowest and highest T(c)'s were selected for breeding. The F1 generation consisted of 10 offspring from the hyperthermic group and 20 from the hypothermic group. They were implanted with transmitters at 60d of age. T(c) of rats derived from the hyperthermic parental line had a significantly warmer T(c) than the rats derived from the hypothermic parental line. Motor activity was significantly higher in the hyperthermic F1 males and hypothermic F1 females. Breeding of hyperthermic and hypothermic rats has shown that adult offspring of the fourth generation maintain significantly different core temperatures but have similar patterns of motor activity. The results demonstrate that T(c) is heritable and that it should be feasible to develop lines of rats that regulate T(c) above or below normal.

Cognitive effects of nicotine.

Nicotine and other nicotinic agonists have been found to improve performance on attention and memory tasks. Clinical studies using nicotine skin patches have demonstrated the efficacy of nicotine in treating cognitive impairments associated with Alzheimer's disease, schizophrenia, and attention-deficit/hyperactivity disorder. Experimental animal studies have demonstrated the persistence of nicotine-induced working memory improvement with chronic exposure, in addition to the efficacy of a variety of nicotinic agonists. Mechanistic studies have found that alpha7 and alpha4beta2 nicotinic receptors in the hippocampus are critical for nicotinic involvement in cognitive function. Clinical and experimental animal studies provide mutually supporting information for the development of novel nicotinic therapies for cognitive dysfunction.

Effects of sweetened ethanol solutions on ethanol self-administration and blood ethanol levels.

The enhancement of voluntary self-administration of ethanol by sucrose or saccharin was tested in conjunction with measurements of blood ethanol levels. Adult male rats were given access to both tap water and one of five solutions: 0.125% saccharin, 10% sucrose, ethanol, saccharin+ethanol, or sucrose+ethanol. The rats receiving the sucrose+ethanol solution drank consistently more ethanol (>5 g/kg/day) than did the rats receiving the saccharin+ethanol solution (<3 g/kg/day) or ethanol only (<2 g/kg/day). Both sweetened solutions produced higher ethanol consumption during these periods than ethanol alone. However, no significant differences in blood ethanol levels were found between the sucrose+ethanol and saccharin+ethanol conditions, when tested at different intervals on Day 44 or Day 45 of ethanol consumption. Following 45 days of consumption, no change in the bicuculline seizure threshold was observed in the ethanol-consuming rats compared to the controls. In a separate study using 90 naive rats, rats were gavaged with ethanol (1, 2, or 3 g/kg) containing either 10% sucrose (n=10 for each dose of ethanol), 0.125% saccharin (n=10 for each dose of ethanol), or ethanol alone (n=10 for each dose of ethanol), and blood was collected from the tip of the tail 30, 60, 180, 300, and 540 min later and analyzed for ethanol concentrations. Sucrose significantly decreased the resultant blood ethanol levels at several time points following gavage. These results indicate that sucrose can significantly alter blood ethanol levels and that chronic self-administration of a sweetened ethanol solution for 6 weeks does not produce ethanol dependence.