Inappropriate drug use rates of geriatric patients attending to a university hospital cardiology policlinic.

BACKGROUND: The interest in risks related to inappropriate drug use (IDU) and polypharmacy among the elderly has increased in recent years. AIMS: We aimed to determine the frequency of IDU and multiple drug use in elderly patients in the cardiology outpatient clinic. PATIENTS AND METHODS: : In this prospective, cross-sectional study, a total of 513 patients aged 65 years and above who were admitted to the Cardiology Policlinic between December 2017 and January 2018 were included. To determine the prevalence of IDU, we investigated the suitability of the drugs used by the patients (according to the criteria of Beers 2015 and Screening Tool of Older People's Prescriptions [STOPP] version 2), the number of violated criteria in both the guidelines and which criterion was violated by the inappropriate drugs. RESULTS: : The 513 patients (mean age: 73.18 ± 5.99) in this study included females (n = 235; 45.8%) and males (n = 278; 54.2%). A total of 2,910 drugs were used by the 513 patients (mean per patient: 5.67 ± 2.51); 52.8% of the patients were using more than five drugs. The Beers criteria revealed that 304 IDUs were detected among the drugs and showed that 38.6% (n = 198) of the patients had IDU. According to the STOPP criteria, 366 IDUs were identified among the drugs used, and 45.6% (n = 234) of the patients had IDU. CONCLUSION: IDU frequencies of the elderly patients are similar to the world literature in our study. As the number of chronic illnesses the patients had increases, the frequency of IDU increases according to Beers and STOPP criteria in our study.

The effects of laserpuncture on gonadal maturity and sperm quality of male striped catfish (Pangasianodon hypophthalmus).

Laserpuncture is one of the applicative technologies used mainly in animal and fish reproductions. Laserpuncture technology has been used to improve gonadal maturity and sperm quality in fish rapidly. This study aimed to determine the effects of different laserpuncture doses on gonadal maturity and sperm quality of male striped catfish. Males striped catfish (800-900 g/fish body weight) and I gonadal maturity stage were used. Semi-conductor soft laser was used with doses of 0.2-, 0.4-, and 0.5-J, while the negative control (without the laserpuncture and the ovaprim™) and only the ovaprim™ were used as a comparison treatment, respectively. The soft-laser was treated on reproductive acupoint every week for four weeks, while the ovaprim™ was administered by intramuscular injection at dose of 0.2 mL/kg fish in final rearing period. Fish was reared in hapa at the controlled pond. Fish was fed with a commercial feed containing 32% crude protein. Gonadal maturity, gonadosomatic index (GSI), hepatosomatic index (HSI), and sperm quality of male striped catfish were measured in the final rearing period. The results showed that the laserpuncture on the reproductive acupoint had a highly significant effect (P < 0.01) on the gonadal maturity, GSI, HSI, and sperm quality of male striped catfish. In terms of the gonadal maturity, laserpuncture doses treatment of 0.4 and 0.5-J gave the most mature IV stage. While the highest levels of GSI and HSI were found in 0.5-J of laserpuncture dose, which was 2.17% and 1.54%, respectively. In addition, the best sperm qualities were observed in 0.5-J of laserpuncture dose, which were 81.75% motility, 82.75% viability, and 7.0 × 109 cell/mL concentration. These results suggest that the laserpuncture can accelerate a gonadal maturity and improve sperm quality in male striped catfish.

A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction.

The purpose of this review is to present up-to-date pharmacological, genetic, and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine, and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein, we sought to place the P rat's behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this chapter discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general.

Effects of ampicillin, cefazolin and cefoperazone treatments on GLT-1 expressions in the mesocorticolimbic system and ethanol intake in alcohol-preferring rats.

Chronic ethanol consumption is known to downregulate expression of the major glutamate transporter 1 (GLT-1), which increases extracellular glutamate concentrations in subregions of the mesocorticolimbic reward pathway. While ß-lactam antibiotics were initially identified as potent upregulators of GLT-1 expression, only ceftriaxone has been extensively studied in various drug addiction models. Therefore, in this study, adult male alcohol-preferring (P) rats exposed chronically to ethanol were treated with other ß-lactam antibiotics, ampicillin, cefazolin or cefoperazone (100mg/kg) once daily for five consecutive days to assess their effects on ethanol consumption. The results demonstrated that each compound significantly reduced ethanol intake compared to the saline-treated control group. Importantly, each compound significantly upregulated both GLT-1 and pAKT expressions in the nucleus accumbens and prefrontal cortex compared to saline-treated control group. In addition, only cefoperazone significantly inhibited hepatic aldehyde dehydrogenase-2 enzyme activity. Moreover, these ß-lactams exerted only a transient effect on sucrose drinking, suggesting specificity for chronically inhibiting ethanol reward in adult male P rats. Cerebrospinal fluid concentrations of ampicillin, cefazolin or cefoperazone have been confirmed using high-performance liquid chromatography. These findings demonstrate that multiple ß-lactam antibiotics demonstrate efficacy in reducing alcohol consumption and appear to be potential therapeutic compounds for treating alcohol abuse and/or dependence. In addition, these results suggest that pAKT may be an important player in this effect, possibly through increased transcription of GLT-1.

Prospective randomized clinical trial of Jean Rives technique versus laparoscopic TEP repair for primary inguinal hernia: 10-year follow-up.

BACKGROUND: The purpose of the present randomized trial was to compare the Jean Rives (JR) technique and the laparoscopic totally extraperitoneal (TEP) repair for the treatment of primary inguinal hernias with respect to operating time, hospital stay, sick leave, chronic pain and recurrences after a follow-up of 10 years. METHODS: 110 patients with primary inguinal hernia were randomized to either a JR repair (53 patients) or to a laparoscopic (TEP) repair (57 patients). All the interventions were exclusively realized by two experienced surgeons. Follow-up examinations were performed after 1, 6 months, 1, 5 and 10 years. RESULTS: Both groups were identical concerning age and hernia type, which were type II and type IIIa according to Nyhus classification. No significant difference was found concerning hospital stay, chronic pain and recurrences. The operating time was significantly lower in JR group, whereas the sick leave was significantly in favor of TEP group. CONCLUSION: Jean Rives technique is a relatively easy technique to perform, requires shorter operating time when compared to laparoscopic TEP technique. JR technique should be taken into consideration while planning surgical treatment of inguinal hernia.

Potential therapeutic drugs and methods for the treatment of amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder caused by damage of motoneurons leading to paralysis state and long term disability. Riluzole is currently the only FDA-approved drug for the treatment of ALS. The proposed mechanisms of ALS include glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, protein aggregation, SOD1 accumulations, and neuronal death. In this review, we discuss potential biomarkers for the identification of patients with ALS. We further emphasize potential therapy involving the uses of neurotrophic factors such as IGFI, GDNF, VEGF, ADNF-9, colivelin and angiogenin in the treatment of ALS. Moreover, we described several existing drugs such as talampanel, ceftriaxone, pramipexole, dexpramipexole and arimoclomol potential compounds for the treatment of ALS. Interestingly, the uses of stem cell therapy and immunotherapy are promising for the treatment of ALS.

Effects of ceftriaxone on systemic and central expression of anti- and pro-inflammatory cytokines in alcohol-preferring (P) rats exposed to ethanol.

AIMS: Determine the effect of reduction in ethanol consumption by alcohol-preferring (P) rats, following ceftriaxone treatment, on the cytokines levels in prefrontal cortex (PFC) and plasma. METHODS: Following 5 weeks of free access to ethanol (15 and 30%), P rats were treated daily with ceftriaxone or saline vehicle for either 2 or 5 consecutive days. Plasma and PFC were collected from ceftriaxone- and saline vehicle-treated groups, and assayed for the levels of pro- and anti-inflammatory cytokines. RESULTS: A significant increase in the plasma level of anti-inflammatory cytokine IL-10 was observed in the ceftriaxone-treated group when compared with the saline-treated group in both the 2-day and 5-day treatments. Furthermore, ceftriaxone treatment for 2 days induced reduction in TNFα level in both plasma and PFC. Additionally, ceftriaxone treatment for 2 days significantly reduced the IFNγ level in PFC. CONCLUSION: These findings show the ability of ceftriaxone to reduce alcohol consumption and induce modulation of the anti-inflammatory and pro-inflammatory cytokines levels in P rats.

Effectiveness of Ceftriaxone Treatment in Preventing Relapse-like Drinking Behavior Following Long-term Ethanol Dependence in P Rats.

OBJECTIVE: To evaluate the effectiveness of ceftriaxone treatment in attenuating relapse-like ethanol drinking behavior in male P rats following 14-weeks of continuous ethanol consumption. METHODS: After 14-weeks of continuous access to free choice of 15% and 30% ethanol, male P rats were deprived of ethanol for two weeks. On the last five days of abstinence period, P rats were treated, once a day, with either saline or ceftriaxone (50 or 200 mg/kg; i.p.). This was followed by re-exposure to ethanol for the next 10 days to simulate the relapse-like ethanol drinking behavior. RESULTS: Ceftriaxone treatment (during abstinence) reduced ethanol intake upon re-exposure to ethanol, compared to the saline treated P rats. This statistically significant reduction in ethanol consumption in P rats following treatment with ceftriaxone (200 mg/kg/day) was observed from Day 2 to Day 9. Similarly, water consumption in P rats treated with ceftriaxone was significantly higher than the saline treated group between Day 2 and Day 7. Importantly, ceftriaxone treatment at both doses did not cause any significant changes in body weight compared to saline treated group. CONCLUSIONS: We report here that ceftriaxone at higher dose has been found to be effective in the attenuation of relapse-like ethanol-drinking behavior in chronic ethanol intake model. This is in accordance with previous data from our lab in cocaine animal model demonstrating that only higher dose of ceftriaxone has been effective in attenuating cocaine relapse.

Effects of ceftriaxone on the acquisition and maintenance of ethanol drinking in peri-adolescent and adult female alcohol-preferring (P) rats.

Increased glutamatergic neurotransmission appears to mediate the reinforcing properties of drugs of abuse, including ethanol (EtOH). We recently reported that the administration of ceftriaxone (CEF), a ß-lactam antibiotic known to upregulate glutamate transporter 1 (GLT1) levels/activity, decreased the maintenance of EtOH intake in adult male alcohol-preferring (P) rats. In the present study, we tested whether CEF administration would reduce the acquisition and maintenance of EtOH drinking in adolescent and adult female P rats. The rats were treated with saline or 200mg/kg ceftriaxone for 7 days (starting at 35 or 75 days old, respectively) followed by the EtOH acquisition test. Five weeks later the effects of CEF were examined regarding the maintenance of EtOH intake. For the maintenance test, half of the animals that received CEF during acquisition received CEF for 7 days and the other half received saline for 7 days. Saline-treated acquisition animals were treated similarly. The results indicated that pretreatment with ceftriaxone reduced the maintenance of EtOH intake in both animals that started as adolescents and those that started as adults. However, the beneficial effect of CEF was more pronounced in rats pretreated with CEF as adults compared with rats pretreated as adolescents. Reductions in EtOH intake by ceftriaxone were paralleled by an upregulation of GLT1 protein levels in both the nucleus accumbens (∼25% in rats starting at both ages) and prefrontal cortex (∼50% in rats starting as peri-adolescents and ∼65% in those starting as adults). These findings provide further support for GLT1-associated mechanisms in high alcohol-consuming behavior, and hold promise for the development of effective treatments targeting alcohol abuse and dependence.

Potential therapeutic role of glutamate transporter 1 for the treatment of alcohol dependence.

INTRODUCTION: Evidence has demonstrated that deficits in glutamate transmission impair neurocircuits involved in drug abuse or drug-seeking behaviour and affect many aspects of neuroplasticity associated with alcohol and drug addiction. Alcohol-seeking behaviour is promoted by increased glutamate transmission in key regions of the mesocorticolimbic reward circuit, including the nucleus accumbens and prefrontal cortex. Glutamate transmission or glutamate uptake is regulated by a number of glutamate transporters in the brain regions. Among these glutamate transporters, glutamate transporter 1 (GLT1; its human homolog is the excitatory amino acid transporter 2, EAAT2) regulates the removal of majority of the extracellular glutamate. The role of GLT1 has been tested in alcohol and other drugs of abuse models with dysfunction in glutamate transmission. We recently reported that treatment of alcohol-preferring rats with compounds ceftriaxone and GPI-1046, known to upregulate GLT1 levels, showed reduction in alcohol intake and attenuation of relapse-like ethanol-drinking behaviour. Furthermore, we demonstrated that upregulation of GLT1 was associated with attenuation of cue-induced cocaine relapse. Together, we suggest that GLT1 is considered as a potential therapeutic target for the treatment of drug dependence, including alcohol. The aim of this critical review was to discuss the potential therapeutic role of GLT1 for the treatment of alcohol dependence. CONCLUSION: Dysfunction of glutamate transmission has been suggested to impair neurocircuits involved in alcohol dependence, which affect neuroplasticity that is associated with ethanol intake.

Neuroimmunophilin GPI-1046 reduces ethanol consumption in part through activation of GLT1 in alcohol-preferring rats.

We have previously shown that ceftriaxone, ß-lactam antibiotic known to upregulate glutamate transporter 1 (GLT1), reduced ethanol intake in alcohol-preferring (P) rats. GLT1 is a glial glutamate transporter that regulates the majority of extracellular glutamate uptake. We tested in this study the effects of neuroimmunophilin GPI-1046 (3-(3-pyridyl)-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidinecarboxylate), known also to upregulate GLT1 expression, in ethanol intake in P rats. Male P rats had concurrent access to free choice of 15% and 30% ethanol, water, and food for five weeks. On Week 6, P rats continued in this drinking and food regimen and they were administered either 10 or 20mg/kg GPI-1046 (i.p.), or a vehicle for five consecutive days. Body weight, ethanol intake, and water consumption were measured daily for 8 days starting on Day 1 of GPI-1046 or vehicle i.p. injections. We have also tested the effect of GPI-1046 (20mg/kg) on daily sucrose (10%) intake. The data revealed significant dose-dependent effects in the reduction of ethanol intake starting 48 h after the first treatment with GPI-1046 throughout treatment and post-treatment periods. There were also dose-dependent increases in water intake. However, GPI-1046 treatment did not affect the body weight of all animals nor sucrose intake. Importantly, GPI-1046 (20mg/kg) increased GLT1 level compared to all groups in nucleus accumbens core (NAc-core). Alternatively, GPI-1046 (10mg/kg) upregulated GLT1 level in NAc-core compared to vehicle (ethanol naïve) group. Moreover, both doses of GPI-1046 increased significantly GLT1 level in the prefrontal cortex (PFC) compared to ethanol naïve vehicle group. GPI-1046 (20mg/kg) increased GLT1 level in PFC compared to naïve control group that was exposed to water and food only. These findings demonstrated that neuroimmunophilin GPI-1046 attenuates ethanol intake in part through the upregulation of GLT1 in PFC and NAc-core.

Glutamate transporter 1: target for the treatment of alcohol dependence.

Emerging evidence indicates that many aspects of alcohol and drug dependence involve changes in glutamate transmission. A number of studies have reported that drugs of abuse, including alcohol and cocaine, alter glutamate transport. Extracellular glutamate is regulated by a number of glutamate transporters in various brain regions. Of these transporters, glutamate transporter (GLT1) is a key player in the removal of most of the extracellular glutamate. Similar to neurodegenerative disease models, in which there is dysfunction of the glutamatergic excitatory system, the role of GLT1 has been tested in drug dependence models that show dysfunction of glutamate transmission. We and others have recently found that ceftriaxone, an FDA-approved drug known to elevate GLT1 expression, attenuates cue-induced cocaine relapse. Moreover, we recently found that alcohol-preferring rats treated with ceftriaxone showed a significant dosedependent reduction in alcohol consumption. We also demonstrated that ceftriaxone-induced upregulation of GLT1 expression was associated with increases in glutamate uptake in Huntington's disease mouse model. Importantly, ceftriaxone is currently in clinical trials for the treatment of amyotrophic lateral sclerosis. This review provides information about the potential therapeutic role of GLT1 for the treatment of alcohol abuse and dependence.

Activity-dependent neurotrophic factor-derived peptide prevents alcohol-induced apoptosis, in part, through Bcl2 and c-Jun N-terminal kinase signaling pathways in fetal brain of C57BL/6 mouse.

Fetal alcohol exposure is known to induce alteration in fetal brain development. In this study, we focused on neuroprotection against the effects of alcohol exposure using ADNF-9, a peptide derived from activity-dependent neurotrophic factor. We used a mouse model of fetal alcohol exposure to identify the intracellular mechanisms underlying the neuroprotective effects of ADNF-9. On embryonic day 7 (E7), weight-matched pregnant females were assigned to the following groups: (1) ethanol liquid diet (ALC) of 25% (4.49%, v/v) ethanol-derived calories; (2) pair-fed control (PF); (3) ALC combined with administration (i.p.) of ADNF-9 (ALC/ADNF-9); and (4) pair-fed combined with administration (i.p.) of ADNF-9 (PF/ADNF-9). On E13, fetal brains were collected, weighed, and apoptosis was determined using TdT-mediated dUTP nick-end labeling (TUNEL) assay. Bcl2 protein and phospho-c-Jun N-terminal kinase (JNK) levels were determined using Western blot and enzyme immunometric assay, respectively. ADNF-9 administration significantly prevented alcohol-induced reductions in fetal brain weight. In addition, ADNF-9 prevented an alcohol-induced increase in cell death in the primordium of the cerebral cortex and ganglionic eminence. Western blot analysis of the mitochondrial protein fractions revealed that ADNF-9 administration prevented an alcohol-induced reduction in the Bcl2 level. Moreover, an analysis of the proteins in the upstream signaling pathway revealed that ADNF-9 downregulated the phosphorylation of JNK. These data indicate that the mitochondrial Bcl2 pathway and JNK upstream signaling pathway are the intracellular targets of ADNF-9. The neuroprotective mechanism of action of ADNF-9 provides a direction for potential therapeutics against alcohol-induced neural damage involving mitochondrial dysfunction.

A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: signaling pathway investigations.

Fetal alcohol exposure is known to induce cell death through apoptosis. We found that colivelin (CLN), a novel peptide with the sequence SALLRSIPAPAGASRLLLLTGEIDLP, prevents this apoptosis. Our initial experiment revealed that CLN enhanced the viability of primary cortical neurons exposed to alcohol. We then used a mouse model of fetal alcohol exposure to identify the intracellular mechanisms underlying these neuroprotective effects. On embryonic day 7 (E7), weight-matched pregnant females were assigned to the following groups: (1) ethanol liquid diet 25% (4.49% v/v) ethanol derived calories; (2) pair-fed control; (3) normal chow; (4) ethanol liquid diet combined with administration (i.p.) of CLN (20 microg/20 g body weight); and (5) pair-fed combined with administration (i.p.) of CLN (20 microg/20 g body weight). On E13, fetal brains were collected and assayed for TdT-mediated dUTP nick end labeling staining, caspase-3 colorimetric assay, enzyme-linked immunosorbent assay, and Meso scale discovery electrochemiluminescence. CLN blocked the alcohol-induced decline in brain weight and prevented alcohol-induced: apoptosis, activation of caspase-3 and increases of cytosolic cytochrome c, and decreases of mitochondrial cytochrome c Analysis of proteins in the upstream signaling pathway revealed that CLN down-regulated the phosphorylation of the c-Jun N-terminal kinase. Moreover, CLN prevented alcohol-induced reduction in phosphorylation of BAD protein. Thus, CLN appears to act directly on upstream signaling proteins to prevent alcohol-induced apoptosis. Further assessment of these proteins and their signaling mechanisms is likely to enhance development of neuroprotective therapies.

Activity-dependent neuroprotective protein-derived peptide, NAP, preventing alcohol-induced apoptosis in fetal brain of C57BL/6 mouse.

Possible prevention of the effects of prenatal alcohol exposure has been investigated using peptides that were previously shown to be involved in neuroprotection both in vitro and in vivo. I focused in this study on investigating the neuroprotective effects of one of these peptides with regard to the determination of the downstream signaling pathways involved in neuroprotection. This peptide with the sequence NAPVSIPQ, known as NAP, a fragment of activity-dependent neuroprotective protein, demonstrated a potent protective effect against oxidative stress associated with alcohol exposure. On embryonic day 7 (E7), weight-matched C57BL/6 pregnant females were assigned the following groups: (1) Ethanol liquid diet group (ALC) 25% (4.49%, v/v) ethano-derived calories, (2) Pair-fed (PF) control group (3) Chow control group, (4) treatment groups with alcohol alongside i.p. injections of d-NAP (ALC/d-NAP, 20 or 30 microg/20 g body weight), (5) PF/d-NAP control group. On E13, fetal brains were collected and assayed for TdT-mediated dUTP nick end labeling (TUNEL) staining, caspase-3 colorimetric assay and ELISA for cytochrome c detection. My results show that NAP significantly prevented alcohol-induced weight reduction of the fetal brain. Apoptosis was determined by TUNEL staining; NAP administration significantly prevented alcohol-induced increases in TUNEL-positive cells in primordium cingulate cortex and basal ganglia eminence. The investigation of downstream signaling pathways involving NAP neuroprotection revealed that this peptide significantly prevented alcohol-induced increase in the concentrations of caspase-3 in E13 fetal brains. Moreover, ELISA for cytochrome c shows that NAP significantly prevented both alcohol-induced increases in the level of cytosolic cytochrome c and alcohol-induced decreases in the level of mitochondrial cytochrome c. These data provide an understanding of NAP intracellular target, and the downstream mechanisms of action that will pave a path toward potential therapeutics against alcohol intoxication during prenatal stages.

Up-regulation of GLT1 expression increases glutamate uptake and attenuates the Huntington's disease phenotype in the R6/2 mouse.

The striatum, which processes cortical information for behavioral output, is a key target of Huntington's disease (HD), an autosomal dominant condition characterized by cognitive decline and progressive loss of motor control. Increasing evidence implicates deficient glutamate uptake caused by a down-regulation of GLT1, the primary astroglial glutamate transporter. To test this hypothesis, we administered ceftriaxone, a beta-lactam antibiotic known to elevate GLT1 expression (200 mg/kg, i.p., for 5 days), to symptomatic R6/2 mice, a widely studied transgenic model of HD. Relative to vehicle, ceftriaxone attenuated several HD behavioral signs: paw clasping and twitching were reduced, while motor flexibility, as measured in a plus maze, and open-field climbing were increased. Assessment of GLT1 expression in striatum confirmed a ceftriaxone-induced increase relative to vehicle. To determine if the change in behavior and GLT1 expression represented a change in striatal glutamate handling, separate groups of behaving mice were evaluated with no-net-flux microdialysis. Vehicle treatment revealed a glutamate uptake deficit in R6/2 mice relative to wild-type controls that was reversed by ceftriaxone. Vehicle-treated animals, however, did not differ in GLT1 expression, suggesting that the glutamate uptake deficit in R6/2 mice reflects dysfunctional rather than missing GLT1. Our results indicate that impaired glutamate uptake is a major factor underlying HD pathophysiology and symptomology. The glutamate uptake deficit, moreover, is present in symptomatic HD mice and reversal of this deficit by up-regulating the functional expression of GLT1 with ceftriaxone attenuates the HD phenotype.

Neurotransmitters and substances of abuse: effects on adult neurogenesis.

Neurogenesis in the adult brain is now a well-recognized phenomenon. The compelling subject of interest now is that besides the intrinsic, what are the environmental factors which affect neural stem cells ability to maintain themselves and enter the pool of the adult brain. While the molecular and cellular mechanisms that regulate this process remain to be elucidated, substantial data implicate common pathways involving action of neurotransmitters through neurotrophic factors to regulate the neural stem cells. This transmitter-mediated neurotrophic factor pathway could be altered by extrinsic environmental factors including enriched environment, exercise, stress, and drug abuse (i.e. alcohol, opioid, methamphetamine). Our special attention focuses on the role of neurotransmitters; among them are serotonin (5-HT), glutamate and gamma-amino-butyric acid (GABA). Substances of abuse including alcohol, which may interact through these neurotransmitters and neurotrophic factors to affect neurogenesis, are also reviewed.

[Acceptability and value of autoinjection of gonadotropins for ovarian stimulation in intrauterine insemination]. / Acceptabilité et intérêt de l'auto-injection de gonadotrophines pour la stimulation en vue d'une insémination intra-utérine.

OBJECTIVES: To evaluate the acceptability, the personal and economic benefit of subcutaneous self-injections of recombinant FSH within mono-ovulating stimulation for Intra Uterine Insemination (IUI). PATIENTS AND METHODS: Women aged < 42 years' old, enrolled for a series of three IIU associated with ovarian stimulation with FSH. All had an infertility > 2 years, at least one patent fallopian tube, and normal FSH and estradiol levels at day three of the cycle. In the male partner, the migration test yielded > 10(6) mobile spermatozoa with survivals > 10% after 24 h. Once entered in the study, the patients (with or without their partners) were informed and shown how to administer the injection. After each cycle, they filled up a questionnaire evaluating the training and the possible difficulties they had with their infertility treatment. RESULTS: Forty women were treated. 103 cycles were achieved (including 40 first cycles, 35 second cycles and 28 third cycles) 99 IUI were performed and ten pregnancies were obtained. Four cycles were cancelled: Premature fall of estradiol levels (n = 2), multiple pregnancy risk (n = 1) and spontaneous ovulation (n = 1). Three pregnancies occurred spontaneously between treatment cycles. All the patients appreciate to perform subcutaneous self-injections (themselves or by the partner) without any deleterious effect on stimulation cycles results and they expressed their will to continue for the next treatment cycles. CONCLUSION: After a quick initiation to subcutaneous injections, and its use, women appreciated their active involvement in the treatment and the self-sufficiency so achieved. By planning an educational program, medical staff could participate to improve the stress experienced by the women and their partners through the infertility treatment.

Fetal alcohol effects: mechanisms and treatment.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Edward P. Riley. The presentations were (1) Does alcohol withdrawal contribute to fetal alcohol effects? by Jennifer D. Thomas and Edward P. Riley; (2) Brain damage and neuroplasticity in an animal model of binge alcohol exposure during the "third trimester equivalent," by Charles R. Goodlett, Anna Y. Klintsova, and William T. Greenough; (3) Ganglioside GM1 reduces fetal alcohol effects, by Basalingappa L. Hungund; and (4) Fetal alcohol exposure alters the wiring of serotonin system at mid-gestation, by F. Zhou, Y. Sari, Charles Goodlett, T. Powrozek, and Ting-Kai Li.