University students' and staff attitudes toward the implementation of a "tobacco-free" policy: A view from Qatar.

Objectives: Tobacco-free campus policies are needed to create environments conducive to prevention or quitting in the Eastern Mediterranean Region (EMR), where the use of various tobacco products is on the rise among university students. The objectives of this study were to assess overall support for a 100% tobacco-free campus policy and its predictors among different stakeholder groups at the largest national university in Qatar and to understand attitudes towards specific policy components. Study design: A cross-sectional online survey of faculty and students. Methods: We measured sociodemographic variables, tobacco use, and support for components of a 100% tobacco-free campus policy. A total score for support was calculated, and associations with selected predictors were assessed using multivariable linear regression. Results: 413 respondents participated in the survey. A majority of faculty/staff and students (76.6% and 75.5%, respectively) supported the implementation of a 100% tobacco-free campus policy, with a majority supporting extension of the policy beyond cigarettes. Support for other components of the policy varied. Among students, overall support was lower among males and tobacco users and higher among the married. Among faculty and staff, support was lower among Qatari nationals and tobacco users. Conclusion: In the context of a growing tobacco crisis in the EMR, implementing and understanding the impact of tobacco-free campus policies is essential. This paper underscores the importance of addressing diverse stakeholder attitudes and providing empirical evidence to guide policy implementation and evaluation.

Clinical Practicum Assessment for Biomedical Science Program from Graduates' Perspective.

The clinical practicum for biomedical science students aims to provide graduates with the knowledge and skills required to work in diagnostic laboratory settings. This study examines graduates' perspectives on content, teachers and clinical training and their satisfaction rates based on the skills gained during training. The study was conducted on females who graduated from Qatar University between 2015 and 2020. We used a previously validated questionnaire called CPAT-QU. Telephonic interviews were conducted and were analyzed using SPSS. The results showed a high satisfaction rate, of 80%, for the content and organization of the clinical training. The participants' main concerns included the evaluation criteria, as 8.7% were not satisfied. The students suggested increasing the length of the training in order to obtain experience that was more practical. The students' satisfaction with the teachers was 70% in terms of their attitude, command of knowledge and ability to convey knowledge. In total, 69.5% of the graduates claimed that their instructors were interested in teaching and 4.4% claimed their instructors conveyed disinterest in teaching. The Qatar University graduates were satisfied with the content of their clinical training. However, they reported some gaps in this training. Identifying these gaps will help in restructuring clinical training to improve student experience.

Factors Affecting Waterpipe Tobacco Smoking among University Students in Qatar.

Background: Recent data show an increase in the prevalence of waterpipe tobacco smoking (WTS) among university students in the Arab Gulf region alongside an attitude of social acceptability and a perception that WTS is less harmful than traditional cigarette smoking. Objective: This study measures the prevalence of WTS among university students and examines the individual, sociocultural, and environmental factors influencing this practice. Methods: Participants were selected through stratified random sampling of students in the largest national university in Qatar. Data were collected anonymously using an online questionnaire. Descriptive univariate and bivariate analyses were conducted to examine the association of WTS with participants' sociodemographic characteristics, knowledge, and attitudes. Results: 199 students completed the questionnaire. Among students who reported using tobacco products, waterpipe (shisha) was the most common product (70.6%). WTS was significantly associated with having a mother (p = 0.015) or a close friend (p < 0.001) who smoked. Compared to non-users, waterpipe tobacco users were significantly more likely to believe that waterpipe tobacco is less addictive than cigarettes (p = 0.009) and significantly less likely to believe that waterpipe tobacco can lead to cardiovascular diseases (p = 0.003) or dental problems (p = 0.02). More waterpipe tobacco users than non-users disagreed that parents (p = 0.005) or advertisements (p = 0.002) could influence use. More waterpipe tobacco users (70%) than non-users (37%) believed that females were more comfortable using waterpipes than cigarettes. Conclusions and implications: The findings shed light on factors shaping WTS and provide evidence for designing multilevel behavioral interventions to decrease the prevalence of WTS among youth.

Prevalence, Risk Factors, Harm Perception, and Attitudes Toward E-cigarette Use Among University Students in Qatar: A Cross-Sectional Study.

Background: Electronic cigarette (e-cigarette) use is becoming more popular worldwide, especially among youth. Studies report that university students have inadequate knowledge as well as misconceptions about the health risks of e-cigarettes, which may lead to their use even in populations where smoking prevalence is relatively low. At this age, the influence of peers is also significant. Understanding attitudes of university students toward the use of e-cigarettes is important for effective tobacco prevention interventions. In this study, we assess the prevalence of e-cigarette use among students in Qatar's largest national university, as well as their knowledge, attitudes, and perceptions of harm in relation to e-cigarettes. Methodology: We conducted a cross-sectional study among Qatar University students using a self-administered online questionnaire. Descriptive univariate analyses were conducted as well as bivariate analyses to check the association of e-cigarette use with variables of interest. A binary logistic regression analysis was conducted to assess determinants of e-cigarette use among students. Results: One hundred ninety-nine students completed the questionnaire. The prevalence of e-cigarette use among students was 14%, with no significant difference by gender (16.2% in males and 12.8% in females). In bivariate analyses, significantly fewer e-cigarette users believed that e-cigarettes cause disease compared to non-users. 67.9% of e-cigarette users compared to 37.6% of non-users believed that e-cigarettes were less harmful than traditional cigarettes, and 78.6% of users compared to 40.4% of non-users believed that their use could be helpful in preventing smoking traditional cigarettes. Bivariate associations between e-cigarette use and knowledge items were significant (p < 0.05) as well as having a smoker among siblings or friends. In the multivariate analysis, only having a friend who was a smoker remained significant after controlling for other variables (OR = 7.3, p < 0.001). Conclusion: Our study found that university students have knowledge gaps and misconceptions with regard to the harms associated with e-cigarettes use, especially among users. A comprehensive smoking prevention policy, educational interventions, and quit support are needed to enhance awareness among university students about the health effects associated with e-cigarettes use. Such interventions should also take into account the influence of peers on smoking practices.

Students' perceptions of a university 'No Smoking' policy and barriers to implementation: a cross- sectional study.

OBJECTIVES: Effective policies are an important tool for reducing tobacco use. We examine student perceptions of the existing no-smoking policy in the country's largest national university and identify perceived barriers to its implementation. We explore student support for a 100% tobacco-free campus policy. DESIGN: We conducted a cross-sectional survey using a self-administered on-line questionnaire. SETTING: This study was conducted at Qatar University (QU), the largest national institution of higher education in Qatar. PARTICIPANTS: A total of 199 students participated out of a stratified random sample of students aged ≥18 years with active registration in the Spring 2020 semester. PRIMARY AND SECONDARY OUTCOME MEASURES: We assessed students' knowledge of and attitudes towards QU's current no-smoking policy, the perceived barriers to its implementation, and support for a 100% tobacco-free policy. RESULTS: Only 26% (95% CI 19.97 to 32.03) and 16.6% (95% CI 11.70 to 22.49) of respondents correctly identified the current policy on traditional and electronic cigarettes, respectively. Less than 30% of respondents held positive attitudes towards policy enforcement, and more male respondents reported positive attitudes towards compliance than women. Support for a 100% tobacco-free policy was at 77.2%, but it was significantly lower among tobacco users compared with non-users (35.9% and 91.8%, respectively; p<0.001). Failure to establish clear penalties, opposition from smoking students, and lack of cessation services were perceived as major barriers to implementation. CONCLUSIONS: Clear and comprehensive tobacco-free policies are important tools for creating environments conducive to rejecting smoking and seeking cessation support. The findings underscore the need to increase awareness about the policy, advocate for clear penalties for violations, and promote cessation services on campus. Qualitative research is needed to further understand perceived barriers to successful enforcement of the policy.

Public practices on antibiotic use: A cross-sectional study among Qatar University students and their family members.

BACKGROUND: Antimicrobial resistance (AMR) is a serious public health problem and a global concern. The inappropriate use of antibiotics has been identified by the World Health Organization as a major risk factor for AMR. METHODS: The purpose of this research study is to assess the prevalence of inappropriate antibiotic use among Qatar University students and their family members, detect sociodemographic factors associated with inappropriate use, evaluate the knowledge and attitude towards antibiotic use, and assess respondents' opinions on healthcare providers' antibiotic prescription practices. Participants (N = 596) completed a self-administered questionnaire. Descriptive analysis, the Pearson chi-squared test, and multivariate logistic regression analyses were performed. RESULTS: The major inappropriate antibiotic use practices followed by the respondents were using antibiotics without prescription (82%), not completing the antibiotic course (45%), and obtaining antibiotics from the pharmacy without prescription (23%). The chi-square test results showed that age (p = 0.031) and nationality (p = 0.041) were associated with using antibiotics without prescription. In addition, respondents less than 21 years of age (p<0.001), who had only a secondary education (p = 0.007), and who lived in one of the large and crowded cities in Qatar (p = 0.011) had higher odds of stopping the antibiotic before completing the course. Our study also revealed that almost 60% of the respondents had inadequate knowledge and a negative attitude towards antibiotic use. Nationality and municipality were the independent factors associated with having appropriate knowledge of antibiotic use. Univariate logistic regression analyses in our study demonstrated that older (>26 years), married and university-graduated participants were more likely to have a positive attitude towards antibiotic use than others. Respondents also reported that neither doctors nor pharmacists were providing adequate patient education about appropriate antibiotic use. The Socio-Ecological Model was applied to interpret the findings and frame implications. CONCLUSION: The findings shed light on various factors shaping antibiotic use practices and provide evidence to design multilevel behavioral interventions to improve public practices of antibiotic use.

Anaphylaxis triggers in a large tertiary care hospital in Qatar: a retrospective study.

BACKGROUND: Anaphylaxis is a serious allergic disease that may lead to death if not immediately recognized and treated. Triggers of anaphylaxis including food, drugs, and insect stings can vary widely. The incidence of anaphylaxis seems to be affected by age, sex, atopy, and geographic location. This study aims to examine the common triggers of anaphylaxis in Qatar. METHODS: A total of 1068 electronic medical records were audited using power chart system: 446 from the medical coding system of anaphylaxis and 622 from the epinephrine auto-injectors (EAIs) dispensed during January 2012-December 2017. RESULTS: Of 1068 patients, 574 (53.5%) had anaphylaxis; male to female ratio was 1.2, and 300 patients (77.9%) were less than 10 years old. The common triggers were food (n = 316, 55.0%), insect stings (n = 161, 28.0%), and drugs (n = 103, 17.9%). Common anaphylaxis food triggers were nuts (n = 173, 30.1%), eggs (n = 89, 15.5%), and seafood (n = 72, 12.5%), and common anaphylaxis medication triggers were antibiotics (n = 49, 8.5%) and nonsteroidal anti-inflammatory drugs (n = 30, 5.2%). Interestingly, 135 anaphylactic patients (23.5%) were due to black ant stings. The anaphylaxis triggers varied significantly between children and adults. Among children (less than 10 years), three quarters of the events were triggered by food (223, 74.3%) while among adults (20-55 years), insect stings (n = 59, 43.0%) and drugs (n = 44, 32.0%) were dominant. DISCUSSION: This is the first national study stratifying anaphylaxis triggers among different age groups in Qatar. This study will serve as a guide for clinical practice in allergy clinics in Qatar and will help to assess future trends of anaphylaxis in Qatar.

Predictors of Continued Breastfeeding at One Year among Women Attending Primary Healthcare Centers in Qatar: A Cross-Sectional Study.

The number of babies in Qatar being exclusively breastfed is significantly lower than the global target set by the World Health Organization. The purpose of this study was to assess knowledge, attitude, and practice (KAP), selected barriers, and professional support as well as their association with continued breastfeeding at one year of age. A sample of Qatari and non-Qatari mothers (N = 195) who attended a well-baby clinic held at primary health care centers in Qatar completed a self-administered questionnaire. Descriptive analysis, the Pearson Chi-squared test, and logistic regression were performed. Around 42% of the mothers stopped breastfeeding when their child was aged between 0 and 11 months old. Mothers who had only one or female child stopped breastfeeding between the ages of 0 and 6 months (p = 0.025, 0.059). The more optimal the breastfeeding practices followed by the mothers, the older the age of the infant when they stopped breastfeeding (p = 0.001). The following factors were inversely associated with breastfeeding duration: the mother's perceptions that she "did not know how to breastfeed," or "wasn't making enough milk," and the need "to return to work/school", with p = 0.022, 0.004, and 0.022, respectively. These findings present factors that should be considered when planning for health education and promotion programs to prolong breastfeeding duration in Qatar.

Functional and evolutionary insight from the crystal structure of rubella virus protein E1.

Little is known about the three-dimensional organization of rubella virus, which causes a relatively mild measles-like disease in children but leads to serious congenital health problems when contracted in utero. Although rubella virus belongs to the same family as the mosquito-borne alphaviruses, in many respects it is more similar to other aerosol-transmitted human viruses such as the agents of measles and mumps. Although the use of the triple MMR (measles, mumps and rubella) live vaccine has limited its incidence in western countries, congenital rubella syndrome remains an important health problem in the developing world. Here we report the 1.8 Å resolution crystal structure of envelope glycoprotein E1, the main antigen and sole target of neutralizing antibodies against rubella virus. E1 is the main player during entry into target cells owing to its receptor-binding and membrane-fusion functions. The structure reveals the epitope and the neutralization mechanism of an important category of protecting antibodies against rubella infection. It also shows that rubella virus E1 is a class II fusion protein, which had hitherto only been structurally characterized for the arthropod-borne alphaviruses and flaviviruses. In addition, rubella virus E1 has an extensive membrane-fusion surface that includes a metal site, reminiscent of the T-cell immunoglobulin and mucin family of cellular proteins that bind phosphatidylserine lipids at the plasma membrane of cells undergoing apoptosis. Such features have not been seen in any fusion protein crystallized so far. Structural comparisons show that the class II fusion proteins from alphaviruses and flaviviruses, despite belonging to different virus families, are closer to each other than they are to rubella virus E1. This suggests that the constraints on arboviruses imposed by alternating cycles between vertebrates and arthropods resulted in more conservative evolution. By contrast, in the absence of this constraint, the strictly human rubella virus seems to have drifted considerably into a unique niche as sole member of the Rubivirus genus.

Epilepsy surgery in a developing country (Lebanon): ten years experience and predictors of outcome.

We present our 10-year experience and preoperative predictors of outcome in 93 adults and children who underwent epilepsy surgery at the American University of Beirut. Presurgical evaluation included video-EEG monitoring, MRI, neuropsychological assessment with invasive monitoring, and other tests (PET, SPECT, Wada). Surgeries included temporal (54%), extratemporal (22%), and multilobar resections (13%), hemispherectomy (4%), vagal nerve stimulation (6%), and corpus callosotomy (1%). Mesial temporal sclerosis was the most common aetiology (37%). After resective surgery, 70% had Engel class I, 9% class II, 14% class III, and 7% class IV. The number of antiepileptic drugs before surgery was the only preoperative factor associated with Engel class I (p=0.005). Despite the presence of financial and philanthropic aid, many patients could not be operated on for financial reasons. We conclude that advanced epilepsy presurgical workups, surgical procedures, and favourable outcomes, comparable to those of developed countries, are achievable in developing countries, but that issues of financial coverage remain to be addressed.

Potential neuroprotective effects of continuous topiramate therapy in the developing brain.

Because antiepileptic drug therapy is usually given chronically with resulting concerns about long-term neurotoxicity, and because short-term topiramate (TPM) therapy has been reported to be neuroprotective against the effects of acute hypoxia, we investigated the long-term effects of continuous TPM therapy during early stages of development. Four groups of rat pups were studied: two sham manipulated normoxia groups and two acute hypoxia groups (at postnatal day [P] 10 down to 4% O(2)), each injected intraperitoneally daily with either vehicle or TPM (30 mg/kg) from P0 to P21. TPM therapy prevented hypoxia-induced long-term (P81) memory impairment (Morris water maze) as well as aggressivity (handling test). The hypoxia group receiving TPM also showed a trend toward reduced CA1 hippocampal cell loss. The aforementioned TPM therapy had no long-term deleterious effects on memory, hyperactivity, or CA1 cell counts in the TPM normoxia group as compared with normal controls.

Quality of life after surgery for intractable partial epilepsy in children: a cohort study with controls.

PURPOSE: Investigate if quality of life (QOL) normalizes on long-term follow-up after surgery for partial epilepsy in children. METHODS: This is a cohort study with controls in which a consecutive cohort of nineteen 2-14-year-old children who underwent focal resections for intractable partial seizures between 1996 and 2006, were matched with 19 non-surgery intractable partial epilepsy patients, and with 19 healthy subjects. The two epilepsy groups were matched for age, sex, socio-economic status (SES), cognitive level, seizure type, and seizure frequency. The healthy group was matched with the two epilepsy groups for age, sex, SES, and cognitive level. QOL was assessed using the QOLCE (Quality of Life in Childhood Epilepsy Questionnaire). RESULTS: In the surgery group (follow-up 3.84+/-2.26 years), 78.9% had Engel class-I versus 21.1% in non-surgery (p=0.01) (follow-up 3.44+/-2.95 years). Surgery patients were similar to healthy subjects in the social, emotional, cognitive, behavioral, and overall QOL (p>0.05) but had lower scores in the total QOL, physical, and health domains (p<0.05). Surgery patients scored better than non-surgery in the behavioral domain and the HASES (Hague Side Effects Scale) score (p<0.05). Non-surgery patients scored worse than healthy in total QOL, physical, behavioral, health, and overall QOL (p<0.05). IQ, HASS (Hague Seizure Severity Scale), and HASES scores were positively associated with total QOL score (p<0.05). Subgroup analysis on seizure-free surgery patients showed that they did not differ from healthy subjects in any of QOL domains (p>0.05, power>0.8). CONCLUSION: Our data indicate that epilepsy surgery for partial seizures in children is associated with better QOL as compared to children with intractable epilepsy who are not operated on, and suggest that in those who achieve seizure freedom normal QOL may at least potentially be possible.

Intravenous immunoglobulin therapy in intractable childhood epilepsy: open-label study and review of the literature.

Our aim was to investigate the long term effectiveness of intravenous immunoglobulin (IVIG) against intractable childhood epilepsy in the era of new antiepileptics and to determine the predictors of a favorable response in a prospective open-label add-on study. Of thirty-seven 9.9+/-0.9-year-old patients (11 with partial seizures, 26 with generalized seizures of whom 9 had West syndrome and 17 Lennox-Gastaut syndrome) followed for 15+/-3 months, 43% had a >50% decrease in seizures (including 15% seizure free, 229+/-58 compared with 104+/-3 seizures/month, P=0.035: generalized 246+/-318 to 117+/-200, P=0.025, partial 191+/-437 to 72+/-179, P>0.05; power=0.2). Males were more likely to respond than females (P=0.011, odds ratio=9.3). Review of the literature revealed nine other articles reporting efficacy of IVIG against epileptic seizures. Only one other used statistical methods and, unlike ours, showed only a trend toward seizure frequency reduction without achieving statistical significance, presumably because it was underpowered. These results indicate large-scale controlled studies of IVIG in epilepsy are still needed.

Membrane structure of CtrA3, a copper-transporting P-type-ATPase from Aquifex aeolicus.

We have produced and characterized two new copper-transporting ATPases, CtrA2 and CtrA3 from Aquifex aeolicus, that belong to the family of heavy metal ion-transporting P(IB)-type ATPases. CtrA2 has a CPC metal-binding sequence in TM6 and a CxxC metal-binding N-terminal domain, while CtrA3 has a CPH metal-binding motif in TM6 and a histidine-rich N-terminal metal-binding domain. We have cloned both copper pumps, expressed them in Escherichia coli and characterized them functionally. CtrA2 is activated by Ag(+) and Cu(+) and presumably transports reduced Cu(+), while CtrA3 is activated by, and presumably transports, the oxidized copper ion. Both CtrA2 and CtrA3 are thermophilic proteins with an activity maximum at 75 degrees C. Electron cryomicroscopy of two-dimensional crystals of CtrA3 yielded a projection map at approximately 7 A resolution with density peaks, indicating eight membrane-spanning alpha-helices per monomer. A fit of the Ca-ATPase structure to the projection map indicates that the arrangement of the six central helices surrounding the ion-binding site in the membrane is conserved, and suggests the position of the two additional N-terminal transmembrane helices that are characteristic of the heavy metal, eight-helix P(1B)-type ATPases.

Programmed cell death in the lithium pilocarpine model: evidence for NMDA receptor and ceramide-mediated mechanisms.

Ceramide is known to induce programmed cell death (PCD) in neural and non-neural tissues and to increase after kainic acid (KA) status epilepticus (SE). Ceramide increases have been shown to depend on NMDA receptor activation in the KA model, but these changes have not been studied in the lithium pilocarpine (LiPC) model. Thus, the purpose of this study was to determine if hippocampal ceramide levels increase after LiPC induced SE and if NMDA receptor blockade prevents PCD and any such ceramide increases. We found that LiPC induced SE resulted in ceramide increases and DNA fragmentation in the hippocampus of adult, P21, and P7 rats. The administration of MK-801, the NMDA receptor antagonist, in adults, 15min prior to pilocarpine, prevented ceramide increases, and DNA fragmentation.

Effects of magnesium sulfate in kainic acid-induced status epilepticus.

Because magnesium has antiseizure effects in some animal models of epilepsy, and possible neuroprotective effects in some models of neuronal injury, we aimed to investigate its effects in the kainic acid (KA) model of status epilepticus (SE) in prepubescent rats. This age was chosen because it is a common age for onset of epilepsy and of SE in humans. Three groups of P35 rats were studied: Group I (MgKA) received magnesium sulfate MgSO4 (270 mg/kg then 27 mg/kg every 20 minutes for 5 hours) and 10 mg/kg KA. Group II (KA) received saline instead of MgSO4 and 10 mg/kg KA. Group III (control) received saline injections only. The dose we used has been shown previously to have anticonvulsant activity in another seizure model. Rats were recorded for their acute behavioral seizures directly after KA, and underwent the handling and Morris Water Maze (MWM) tests on P96-97 and P102-106 respectively. The MgKA and the KA groups did not differ in their acute seizures and both showed similar histologic lesions in CA3/CA4 and CA1 hippocampal subfields, and were more aggressive on the handling test than control rats. The MgKA group took more time to reach the platform in MWM than controls, while the KA group scores were intermediate between the two groups. Using the dose of 540 mg/kg MgSO4 and 54 mg/kg every 20 min showed the similar result of lack of protection against impairment in long-term memory. We conclude that (1) Magnesium did not manifest acute behavioral antiseizure effects in the KA P35 model of SE. (2) Magnesium did not prevent the tested long-term behavioral and histological consequences of SE in this model.

Long-term effects of acute and of chronic hypoxia on behavior and on hippocampal histology in the developing brain.

Ten-day-old rat pups (P10) subjected to acute hypoxia (down to 4% O2) had as adults increased aggression (handling test), memory impairment (water maze test), and decreased CA1 cell counts. Pups subjected to chronic hypoxia (10% O2 from P0 to P21) had increased aggression, hyperactivity (open-field test), and decreased CA1 cell counts. Chronic hypoxia with superimposed acute hypoxia resulted in consequences that were not different from those of chronic hypoxia.

The basic framework of VE-cadherin junctions revealed by cryo-EM.

Artificial adherens junctions were reconstituted in vitro by assembly of cadherin fragments at the surfaces of liposomes. The architecture of the adherens junctions was revealed by cryo-electron microscopy (cryo-EM). The formation of these artificial adherens junctions was shown to result from the two-dimensional (2D) self-assembly of cadherin fragments at membrane surfaces. The molecular architecture of the junctions was resolved by combining information from several cryo-EM views. This study concludes to the 2D ordered nature of the cadherin assembly and shows that the minimal information required to build up an adherens junction is contained within the extracellular moiety of cadherin molecules.

A soluble VE-cadherin fragment forms 2D arrays of dimers upon binding to a lipid monolayer.

A high concentration of cadherin molecules at cell-cell adhesion sites is believed to be essential for generating strong intercellular junctions. In order to determine the interactions of cadherin domains involved in the early stages of lateral cluster formation on the cell surface, a recombinant fragment encompassing the first four domains of human VE-cadherin with a His-tag at the C terminus (VE-EC1-4-His) was produced. Two-dimensional crystals of VE-EC1-4-His were formed at the air-water interface using conventional lipids modified to contain a Ni(2+)-chelating group, which provides a specific site for interaction with the polyhistidine tag. The VE-EC1-4-His was monomeric at the concentration employed for crystal formation; however, the crystals exhibited a p2 symmetry and the presence of cis-dimer interactions between symmetry-related molecules. The VE-EC1-4-His molecules in the crystalline array have a remarkably compact conformation in contrast to the elongated "string of pearls" conformation seen in the hexameric assembly of VE-EC1-4-His in solution, and as seen in the crystal structure of C-cadherin. These results indicate that VE-cadherin can exist in at least two oligomeric states with different interactions between domains and can adopt highly different conformational states. We suggest that the compact cis-dimeric state may occur on isolated cells and that the compact form may serve to protect the molecule from degradation. As previously proposed we suppose that the trans-hexameric form is involved in intercellular adhesion.

Hippocampal programmed cell death after status epilepticus: evidence for NMDA-receptor and ceramide-mediated mechanisms.

PURPOSE: Status epilepticus (SE) can result in acute neuronal injury with subsequent long-term age-dependent behavioral and histologic sequelae. To investigate potential mechanisms that may underlie SE-related neuronal injury, we studied the occurrence of programmed cell death (PCD) in the hippocampus in the kainic acid (KA) model. METHODS: In adult rats, KA-induced SE resulted in DNA fragmentation documented at 30 h after KA injection. Ceramide, a known mediator of PCD in multiple neural and nonneural tissues, increased at 2-3 h after KA intraperitoneal injection, and then decreased to control levels before increasing again from 12 to 30 h after injection. MK801 pretreatment prevented KA-induced increases in ceramide levels and DNA fragmentation, whether there was reduction in seizure severity or not (achieved with 5 mg/kg and 1 mg/kg of MK801, respectively). RESULTS: Both ceramide increases and DNA fragmentation were observed after KA-induced SE in adult and in P35 rats. Ceramide did not increase after KA-induced SE in P7 pups, which also did not manifest any DNA fragmentation. Intrahippocampal injection of the active ceramide analogue C2-ceramide produced widespread DNA fragmentation, whereas the inactive ceramide analogue C2-dihydroceramide did not. CONCLUSIONS: Our data support the hypotheses that (a) N-methyl-d-aspartate-receptor activation results in ceramide increases and in DNA fragmentation; (b) ceramide is a mediator of PCD after SE; and (c) there are age-related differences in PCD and in the ceramide response after SE. Differences in the ceramide response could, potentially, be responsible for observed age-related differences in the response to SE.