Effects of zolpidem on sedation, anxiety, and memory in the plus-maze discriminative avoidance task

Rationale

Zolpidem (Zolp), a hypnotic drug prescribed to treat insomnia, may have negative effects on memory, but reports are inconsistent.

Objectives

We examined the effects of acute doses of Zolp (2, 5, or 10 mg/kg, i.p.) on memory formation (learning, consolidation, and retrieval) using the plus-maze discriminative avoidance task.

Methods

Mice were acutely treated with Zolp 30 min before training or testing. In addition, the effects of Zolp and midazolam (Mid; a classic benzodiazepine) on consolidation at different time points were examined. The possible role of state dependency was investigated using combined pre-training and pre-test treatments.

Results

Zolp produced a dose-dependent sedative effect, without modifying anxiety-like behavior. The pre-training administration of 5 or 10 mg/kg resulted in retention deficits. When administered immediately after training or before testing, memory was preserved. Zolp post-training administration (2 or 3 h) impaired subsequent memory. There was no participation of state dependency phenomenon in the amnestic effects of Zolp. Similar to Zolp, Mid impaired memory consolidation when administered 1 h after training.

Conclusions

Amnestic effects occurred when Zolp was administered either before or 2–3 h after training. These memory deficits are not related to state dependency. Moreover, Zolp did not impair memory retrieval. Notably, the memory-impairing effects of Zolp are similar to those of Mid, with the exception of the time point at which the drug can modify consolidation. Finally, the memory effects were unrelated to sedation or anxiolysis.     

Reassortant Influenza A(H1N1)pdm09 Virus in Elderly Woman,Denmark, January 2021

A case of human infection with influenza A(H1N1)pdm09 virus containing a nonstructural gene highly similar to Eurasian avian-like H1Nx swine influenza virus was detected in Denmark in January 2021. We describe the clinical case and report testing results of the genetic and antigenic characterizations of the virus.     

Real-life data of survival and reasons for discontinuation of biological disease-modifying drugs ‘in’ rheumatoid arthritis

Background Rheumatoid arthritis is a chronic, autoimmune disease in which treatment has evolved with a variety of therapeutic classes. Biological disease-modifying antirheumatic drugs have improved therapy; however, the continued long-term use of these drugs with sustained safety and efficacy remains a challenge. ObjectiveThe objective of this study was to analyze time of use and reasons for discontinuation of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.SettingIt is as part of REAL (Rheumatoid Arthritis in Real Life), a multicenter project that evaluated Brazilian patients with rheumatoid arthritis in a real-life setting. Eleven referral centers for the treatment in the public network participated in the study.MethodsWe conducted a cross-sectional analysis of data collected in the REAL study from August to October 2015 study. The patients were submitted to clinical evaluation and analysis of medical records.Results1125 patients were included (89.5% women; median age: 56.6 years; and disease time: 12.8 years). A total of 406 (36.09%) participants were on a biological disease-modifying antirheumatic drugs. Infliximab was the drug with the longest time of use (12 years). Most (64.4%) drug suspension episodes were due to inefficacy. Adalimumab and certolizumab had a greater number of suspensions due to primary inefficacy, while discontinuations for abatacept were due more to secondary inefficacy. Infliximab had fewer suspensions due to primary inefficacy and golimumab had fewer episodes of secondary inefficacy. Regarding side effects, infliximab was suspended a greater number of times because of clinical and laboratory side effects. Abatacept and adalimumab had fewer suspensions due to clinical side effects, and certolizumab, rituximab and tocilizumab had fewer laboratory adverse effects. Conclusion Among the biological disease-modifying antirheumatic drugs being used for long periods, infliximab had greater time of use. Most drug suspensions (64%) were due to primary or secondary inefficacy. Number of discontinuations due to clinical and laboratory adverse effects for each drug was analyzed, and these data should be confirmed by other real-life studies. Knowledge of what is happening in real life is essential to health professionals, who need to be aware of the most common adverse effects and to health managers, who aim for greater cost-effectiveness in the choice of medications.

     

Photodynamic therapy agent with a built-in apoptosis sensor for evaluating its own therapeutic outcome in situ

Identifying the extent of apoptosis in cells or tissues after cancer therapy in real time would be a powerful firsthand tool for assessing therapeutic outcome. We combined therapeutic and imaging functions in one agent, choosing photodynamic therapy (PDT) as an appropriate cancer treatment modality. This agent induces photodamage in irradiated cells and simultaneously identifies apoptotic cells by near-infrared fluorescence. This photodynamic therapy agent with a built-in apoptosis sensor (PDT-BIAS) contains a fluorescent photosensitizer used as an anticancer drug, connected to a fluorescence quencher by a caspase-3 cleavable peptide linker. We demonstrated that cleavage of the peptide linker by caspase-3, one of the executioner caspases involved in apoptosis, results in a detectable increase of fluorescence in solution and in cancer cells after PDT treatment. The apoptosis involvement and drug effectiveness were confirmed by Apoptag and cell viability (MTT) assays supporting the ability of PDT-BIAS to induce and image apoptosis in situ.     

A phase I Study with oral SU5416 in patients with advanced solid tumors: A drug inducing its clearance

Summary Vascular endothelial growth factor (VEGF) is a potent stimulant of angiogenesis. SU5416, is a small molecule tyrosine kinase inhibitor, and a potent inhibitor of VEGF- mediated Flk-1 receptor signaling. Intravenous agent SU5416 has shown evidence of biological activity against a variety of tumor types. The current intravenous dosing regimen is not optimal for long-term administration, which is needed for optimal efficacy. The aim of this study was to evaluate the safety profile and pharmacokinetics of a Nanocrystal Colloidal Dispersion^TM (NCD) SU5416 formulation in humans. Patients with advanced and/or metastatic solid organ tumors were included in the trial; various SU5416 regimens were tested for tolerability, safety and were evaluated concerning pharmacokinetics. The results of this study indicate that induction of clearance after oral dosing of NCD SU5416 in humans occurs and is greater than following IV administration. It has been confirmed that SU5416 is a high clearance compound, also as an oral NCD formulation. The NCD formulation was well tolerated, but no effective drug serum levels could be achieved. These data help to understand the ADME (Absorption, Distribution, Metabolism, Excretion) properties of indoline chemical class compounds. The lessons learned should be applied in the development of next generation indoline anti-angiogenic and anti-tumor compounds.     

Comet assay on gill cells and hemocytes from the blue mussel Mytilus edulis

Gill cells and hemocytes from the blue mussel Mytilus edulis were examined for DNA damage using the comet assay after laboratory exposure in vitro and in vivo to methyl methansulfonate (MMS). Hydrogen peroxide and UV radiation were used as positive control. Comet assay was also carried out on hemocytes from blue mussels sampled at polluted and unpolluted coastal areas. After 60 min in vitro exposure of gill cells to MMS, the highest response, a tail moment of 6.70+/-4.25, was obtained at 1.0mg/L. At higher doses the response decreased. After 2 days in vivo exposure a dose response was seen at concentrations between 1.0 and 33.0mg/L MMS for both gill cells and hemocytes. However, after 4 days in vivo exposure using the same concentrations of MMS, a maximum effect was seen at a 10 times lower concentration of 3.3mg/L. At the higher doses, the effect decreased. Hemocytes from blue mussels sampled at four polluted sites in K?ge Bay had a great variation in tail moments with the highest value of 5.38+/-4.39. The average of all samples from K?ge Bay had tail moments of 2.75+/-1.00(n=19), which was significantly higher (P<0.05) than the average, 1.72+/-1.16(n=10), of samples from unpolluted coastal waters.     

Inter-subjectivity in the context of people with cystic fibrosis' family

This is a qualitative investigation with a phenomenological approach, which aimed to reveal the inter-subjective processes in the context of the family in which there is a person who suffers from Cystic Fibrosis (CF). Fourteen families of CF carriers were interviewed. They were registered at the Paranaense Association of Cystic Fibrosis Care, and lived in the north and northwest regions of Paraná estate (PR), Brazil. Significant units were taken from their speech and grouped into three categories: Family, Carrier of CF and the other; Religious aspects about the life of the CF carrier in the family; Carrier of CF in the scholar, professional and affective life. The results confirmed that families' experience shared with the other was crucial to face the disease. Knowing the inter-subjective processes that underlie the core of the family of people affected by CF provides a new way of working in nursing.     

Epidemiological profile of cocaine users on treatment in psychiatrics hospitals, Brazil

OBJECTIVE: To describe the epidemiological profile and patterns of cocaine use among hospitalized drug users. METHODS: A cross-sectional study was carried out among drug users, aged 18 years or more, hospitalized in one out six selected psychiatric hospitals in the metropolitan area of Greater S o Paulo, whose clinical conditions allowed them to reliably answer to a standardized questionnaire and who agreed to participate. Six psychiatric hospitals who attended spontaneously referred public and private patients from all Greater S o Paulo were selected. Data collection was conducted using structured interviews, individually applied by a trained psychologist. Statistical analysis was performed using Student t-test and Chi-square test at p<0.05. RESULTS: There was a predominance of crack use (38.4%) over intravenous drug use (1.6%). Addicts who smoked cocaine had lower education, most were unemployed and had previously lived on the streets, and used higher amounts of drugs. These addicts also had been previously incarcerated more often than addicts who used other routes for drug administration. CONCLUSIONS: Drug use is a serious public health problem in Greater S o Paulo, and this is shown by the great amount of hospital admissions due to drug addiction. Crack users have lower socioeconomic status and more often engage in violence and crimes.     

Factors associated with secondary breast cancer prevention in Maringá, Paraná State, Brazil

This study analyzed the prevalence of secondary breast cancer prevention and associated factors in women 40 to 69 years of age in Maringá, Paraná State, Brazil. Prevalence was 64.5% for breast self-examination, 71.5% for clinical examination, and 79% for mammography. The data suggest that age, schooling, ethnicity, socioeconomic status, religion, and prior hormone replacement therapy influenced the rates of the three types of examination. Preventive practices were significantly more common among women of higher socioeconomic status. Proper orientation and performance of preventive measures and tests should be at the reach of all women in the highest-risk age bracket, thereby decreasing late diagnosis and avoidable deaths and increasing the odds of curing breast cancer.     

Socio-political aspects of the implantation of the Transplant Center of Piauí

A qualitative study aiming at understanding the socio-political aspects that mediate the implantation of the Transplant Center of Piauí, identify the social topics involved in this implantation and analyze the participation of the organized civil society. Ten people directly related to the implantation of the transplant center were involved in the study, selected through the "snowball" technique. A loosely structured interview, taped, transcribed and submitted for thematic analysis was used. It was concluded that the implantation of the transplant center in Piauí was the fruit of a complex series of negotiations and interests among the State and organized civil society, as there was no political project for action in the area of transplants. This distancing from the responsibility of the public sector characterizes the importance that was given to this implantation.