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Objective: To explore the effectiveness of minimally invasive surgical treatment for pancreatic acinar cell carcinoma (PACC). Methods: Six patients with PACC diagnosed in Peking University Third Hospital from January 2010 to September 2022 were retrospectively selected. Preoperative evaluation was performed on whether the lesions were eligible for surgery, including whether radical resection of liver metastases could be performed. Laparoscopic or Da Vinci robot-assisted resection was performed on six patients, and spleen retention was determined according to the original lesions and the relationship with peripheral blood vessels and tissues, while simultaneous resection was performed on cases of peripheral organ tissue invasion. The patients' basic information, preoperative general conditions, preoperative diagnosis and tumor stage, minimally invasive surgery methods, postoperative complications, pathological results, tumor stage and follow-up data were collected and analyzed to explore the effectiveness of minimally invasive surgery. Results: Among the six patients, four were males and two were females, with the age of 25-69 years. Five patients had abdominal pain and distension before surgery, five patients had tumors located at the tail of the pancreatic body, and one patient had tumors located at the head of the pancreas. Preoperative imaging (enhanced CT and MRI) was performed to measure the tumor diameter (2.8-10.0 cm). Tumor markers were elevated in two patients before surgery, and six patients underwent surgery through laparoscopy or robotic platform. No complications such as postoperative pancreatic fistula and bleeding were clinically relevant during and after surgery. There were two cases with concurrent or heterochronous liver metastasis, two cases with lymph node metastasis and nodular metastasis, four cases with tumor invasion of surrounding organs (stomach, spleen or duodenum), and three cases with vascular cancer thrombi. The follow-up time of the six patients was 12 to 165 months, and one patient underwent three operations due to postoperative liver metastasis and residual pancreatic recurrence, and the results were satisfactory. All the six patients survived at the last follow-up. Conclusions: PACC is prone to invade the surrounding organs, and has a large tumor diameter. Radical surgery for PACC can be completed through minimally invasive surgery, and satisfactory oncology prognosis can be obtained. In addition, some PACC patients with recurrence and metastasis can still be treated by surgery.
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Carcinoma de Células Acinares , Laparoscopia , Neoplasias Hepáticas , Neoplasias Pancreáticas , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Carcinoma de Células Acinares/cirurgia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Hepáticas/cirurgiaRESUMO
The Dzyaloshinsky-Moriya interaction (DMI) at the Co/h-BN interface can emerge and be enhanced by applying a downward electric field. The height of the Co atom relative to the h-BN layer with the electric field determines the variation of DMI. One half reduction of J1 is beneficial to generate skyrmions. Tuning the DMI by an electric field sheds new light for research on skyrmions.
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Biological probes with integrated photoluminescence and magnetism characteristics play a critical role in modern clinical diagnosis and surgical protocols combining fluorescence optical imaging (FOI) with magnetic resonance imaging (MRI) technology. However, traditional magnetic semiconductors can easily generate a spin splitting at the Fermi level and half-metallic electronic occupation, which will sharply reduce the radiation recombination efficiency of photogenerated carriers. To overcome this intrinsic contradiction, we propose a controllable oxidation strategy to introduce some particular PîO bonds into black phosphorus nanosheets, in which the p orbital hybridization between P and O atoms not only provides some carrier recombination centers but also leads to a room-temperature spin polarization. As a result, the coexistence of photoluminescence and magnetism is realized in multifunctional black phosphorus probes with excellent biocompatibility. This work provides a new insight into integrating photoluminescence and magnetism together by intriguing atomic orbital hybridization.
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ABSTRACT: Objective To study the changes of metabolites in serum and tissues ï¼kidney, liver and heartï¼ of mice died of acute tetracaine poisoning by metabolomics, to search for potential biomarkers and related metabolic pathways, and to provide new ideas for the identification of cause of death and research on toxicological mechanism of acute tetracaine poisoning. Methods Forty ICR mice were randomly divided into control group and acute tetracaine poisoning death group. The model of death from acute poisoning was established by intraperitoneal injection of tetracaine, and the metabolic profile of serum and tissues of mice was obtained by ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry ï¼UPLC-Orbitrap HRMSï¼. Multivariate statistical principal component analysis ï¼PCAï¼ and orthogonal partial least square-discriminant analysis ï¼OPLS-DAï¼ were used, combined with t-test and fold change to identify the differential metabolites associated with death from acute tetracaine poisoning. Results Compared with the control group, the metabolic profiles of serum and tissues in the mice from acute tetracaine poisoning death group were significantly different. Eleven differential metabolites were identified in serum, including xanthine, spermine, 3-hydroxybutylamine, etc.; twenty-five differential metabolites were identified in liver, including adenylate, adenosine, citric acid, etc.; twelve differential metabolites were identified in heart, including hypoxanthine, guanine, guanosine, etc; four differential metabolites were identified in kidney, including taurochenodeoxycholic acid, 11, 12-epoxyeicosatrienoic acid, dimethylethanolamine and indole. Acute tetracaine poisoning mainly affected purine metabolism, tricarboxylic acid cycle, as well as metabolism of alanine, aspartic acid and glutamic acid. Conclusion The differential metabolites in serum and tissues of mice died of acute tetracaine poisoning are expected to be candidate biomarkers for this cause of death. The results can provide research basis for the mechanism and identification of acute tetracaine poisoning.
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Metabolômica , Tetracaína , Animais , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Metaboloma , Camundongos , Camundongos Endogâmicos ICRRESUMO
ABSTRACT: Objective To study the influence of halogenated hydroxyl-alkanes inhalation anesthetic on the determination of ethanol content in blood. Methods Halogenated hydroxyl-alkanes were analyzed by headspace gas chromatography with double column confirmatory detection method. The influence of halogenated hydroxyl-alkanes on determination of ethanol content in blood sample by headspace gas chromatography was explored under the different detection conditions of KB-BAC1/ KB-BAC2 and J&W DB-ALC1/DB-ALC2 gas chromatographic column. Results The retention time of sevoflurane and enflurane was similar to that of ethanol and tert butanol respectively when using the J&W DB-ALC1/DB-ALC2 gas chromatographic column, and interfered with the detection of ethanol content in blood; only J&W DB-ALC1 gas chromatographic column can separate the sevoflurane and ethanol components, so as to eliminate their influence on the detection of ethanol content in blood. When using KB-BAC1/KB-BAC2 gas chromatographic column, the retention time of sevoflurane, isoflurane and ethanol is similar, especially that of sevoflurane and ethanol, and sevoflurane obviously interferes with the determination of ethanol content in blood. Conclusion Halogenated hydroxy-alkanes interfere with determination of ethanol content in blood by headspace gas chromatography. The interference can be discriminated effectively by choosing the suitable chromatographic column and double column confirmatory detection.
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Anestésicos Inalatórios , Isoflurano , Alcanos , Etanol , SevofluranoRESUMO
OBJECTIVES: To develop a method to screen and quantify 10 common herbicides ï¼paraquat, diquat, glyphosate, glufosinate, cyanazine, atrazine, metazachlor, acetochlor, chlorsulfuron, and metsulfuronï¼ in blood. METHODS: With acetonitrile-water solution [Vï¼acetonitrileï¼â¶Vï¼waterï¼=3â¶1] as protein precipitant, 10 common herbicides in blood were detected using ultra-high performance liquid chromatography-high resolution mass spectrometry ï¼UPLC-HRMSï¼. RESULTS: All the 10 herbicides had good linearity in their linear range ï¼coefficient of determination R2≥0.993ï¼, with the recovery rates 67.4%-111.9%, the relative standard deviations 1.5%-10.8%, the accuracies 85.1%-106.1%, intra-day precisions 2.7%-13.5%, and inter-day precisions 3.3%-13.3%. CONCLUSIONS: This method is easy to operate with high recovery rates. It enables rapid and accurate qualitative screening and quantitative analysis of various herbicides in blood simultaneously.
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Herbicidas , Cromatografia Líquida de Alta Pressão , Herbicidas/sangue , Espectrometria de Massas , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Inherited epidermodysplasia verruciformis (EV) is a rare skin disorder characterized by susceptibility to specific types of human papilloma virus (HPV) and is strongly associated with skin carcinomas. Inactivating mutations in EVER1/EVER2 account for most cases of EV. However, more phenotypes related to but distinct from EV have been reported with an immunodeficiency state but without EVER1/EVER2 mutation, and the genetic basis for these atypical EV cases is poorly understood. OBJECTIVES: To identify the causative gene responsible for three siblings affected by atypical EV but without EVER1/EVER2 mutation. METHODS: Whole-exome sequencing followed by Sanger sequencing was performed to identify the gene responsible for the patients with atypical EV enrolled in our study. RESULTS: A homozygous splicing mutation was detected in LCK (c.188-2A>G). This mutation resulted in an exon 3 deletion T lymphocyte-specific protein tyrosine kinase isoform, which further led to frameshift mutation and subsequent mRNA decay. CONCLUSIONS: We demonstrate a novel mutation in LCK in a family affected by atypical EV with T-cell defects, HPV infection and virus-induced malignancy, providing new clues in the understanding of host defences against HPV and better genetic counselling of patients with the EV phenotype.
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DNA Recombinante/genética , Epidermodisplasia Verruciforme/genética , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Mutação/genética , Infecções por Papillomavirus/genética , Dermatopatias/genética , Adolescente , Feminino , Homozigoto , Humanos , Masculino , Linhagem , Adulto JovemRESUMO
BACKGROUND: The purpose of this study was to evaluate the risk of acute pancreatitis following pneumococcal pneumonia in Taiwan. METHODS: We undertook a retrospective cohort study using the hospitalisation claims data of the Taiwan National Health Insurance Program. We identified 16709 subjects aged 20-84 with the first-attack of pneumococcal pneumonia between 1998 and 2010 as the pneumonia group and we randomly selected 66836 subjects without a history of pneumonia as the non-pneumonia group. Both groups were matched for gender, age and index year. We examined the incidence of acute pancreatitis by the end of 2010 and we used a multivariable Cox proportional hazards regression model to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of acute pancreatitis associated with pneumococcal pneumonia and other comorbidities. RESULTS: Subjects with pneumococcal pneumonia had higher incidence of acute pancreatitis, when compared with non-pneumonia subjects (2.41 vs. 1.47 per 1000 person-years, crude HR 1.65, 95% CI=1.38, 1.97). The highest risk of developing acute pancreatitis occurred during the first 3 months after diagnosing pneumococcal pneumonia (crude HR 4.11, 95% CI 1.98, 8.52). After adjusted for potential confounders, the adjusted HR of acute pancreatitis was 1.51 (95% CI 1.25, 1.82) for the pneumonia group, as compared with the non-pneumonia group. CONCLUSIONS: Overall, this study reveals a 51% increased hazard of acute pancreatitis following infection with pneumococcal pneumonia. Patients with pneumococcal pneumonia should receive close surveillance for risk of developing acute pancreatitis during the first 3 months after diagnosing pneumococcal pneumonia.
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Pancreatite/epidemiologia , Pneumonia Pneumocócica/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Grupos Diagnósticos Relacionados/estatística & dados numéricos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pancreatite/complicações , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To identify the risk factors for death of elderly patients with acute obstructive suppurative cholangitis (AOSC). METHODS: Three hundred and forty-eight AOSC patients > 60 years of age were retrospectively analysed in the First People's Hospital of Jining from June 2005 to June 2013. The patients were treated with endoscopic retrograde cholangiopancreatography (ERCP) immediately after AOSC was diagnosed to clear the stones and drain, and surgical procedures were then performed in the patients in whom ERCP failed. The risk factors were identified with univariate and multivariate analysis. RESULTS: Among the 348 AOSC patients, 27 patients died after treatment. Two hundred and forty-nine patients were treated with ERCP, and 11 patients died; 99 patients were treated with ERCP plus surgery, and 16 patients died. Two hundred and thirty-two patients were treated within 24 hours after they were admitted to the hospital, and 10 patients died; 116 patients were treated beyond 24 hours, and 17 patients died. According to the results of the univariate and multivariate analysis, shock, ERCP plus surgery, advanced age, low platelet count, the presence of co-morbidities, door to treatment time > 24 hours, hypoproteinaemia, and hyperbilirubinaemia were the independent risk factors for death of elderly patients with AOSC. CONCLUSION: The strategies of dealing with these risk factors should be researched to reduce mortality of elderly patients with AOSC.
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Objective: To understand the influence of unhealthy lifestyle on diabetic dyslipidemia and the key influencing factors in occupational population and provided scientific evidence for the prevention of diabetic dyslipidemia. Methods: Based on baseline data and follow-up data of Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd. during 2021. Diabetic dyslipidemia was defined as diabetes plus one or more forms of dyslipidemia, and unhealthy lifestyle factors included smoking, alcohol consumption, unhealthy dietary patterns, low physical activity, and abnormal BMI. Multivariate logistic regression model was used to analyze the relationship between unhealthy lifestyle scores and diabetic dyslipidemia, network analysis was used to find and explore the key lifestyles influencing glycolipid metabolism. Results: A total of 25 631 subjects were included. People with unhealthy lifestyle score 2 and 3 were 1.93 (95%CI: 1.31-2.86) times and 2.37 (95%CI: 1.60-3.50) times more likely to have diabetes with ≥1 forms of dyslipidemia than those with scores of 0; People with unhealthy lifestyle score 1, 2 and 3 were 1.98 (95%CI: 1.08-3.61) times, 2.87 (95%CI: 1.60-5.14) times and 3.95 (95%CI: 2.22-7.06) times more likely to have diabetes with ≥2 forms of dyslipidemia than those with score 0. Network analysis found that abnormal BMI and HDL-C were the "bridge nodes" that link unhealthy lifestyles with diabetic dyslipidemia. Conclusion: The higher the score of unhealthy lifestyle, the higher the risk for diabetic dyslipidemia, abnormal BMI and HDL-C are key factors influencing the association between unhealthy lifestyle and diabetic dyslipidemia.
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Diabetes Mellitus , Dislipidemias , Humanos , Estilo de Vida , Diabetes Mellitus/epidemiologia , Fumar/epidemiologia , Consumo de Bebidas Alcoólicas/epidemiologia , Dislipidemias/epidemiologia , Fatores de RiscoRESUMO
Objective: To understand the relationship between unhealthy lifestyle and hyperuricemia, as well as the modification effects of hypertension and dyslipidemia in occupational population and provide a theoretical basis for the prevention of hyperuricemia. Methods: A cross-sectional survey design was adopted, based on baseline data from the Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd., which included the population in 28 prefectures from Sichuan Province and Guizhou Province, and 33 districts (counties) from Chongqing Municipality between October and December 2021. This study collected the information about the demographics characteristics, lifestyles, and prevalence of chronic non-communicable diseases of the study subjects through questionnaire, physical measurement and laboratory biochemical test. The unhealthy lifestyle score was scored based on smoking, alcohol consumption, dietary patterns, physical activity, and low weight or overweight, with higher scores being associated with more unhealthy lifestyles. The multivariate logistic regression model was used to analyze the relationship between unhealthy lifestyle score, smoking, alcohol consumption, other factors and hyperuricemia, and the stratified analysis was used to explore the modification effect of hypertension and other diseases on the relationship between unhealthy lifestyle and hyperuricemia. Results: A total of 11 748 participants were included in this study, the prevalence of hyperuricemia was 34.4%. Multivariate logistic regression model showed that current/previous smoking, current/previous alcohol consumption and BMI abnormality were risk factors for hyperuricemia, and the unhealthy lifestyle score showed a "cumulative" effect on the risk for hyperuricemia, with higher score increasing the risk of hyperuricemia, and the OR increased from 1.64 (95%CI: 1.34-2.00) to 2.89 (95%CI: 2.39-3.50). Stratified analysis showed that unhealthy lifestyles had a greater impact on the risk for hyperuricemia in people with hypertension and dyslipidemia. Conclusions: The coexistence of multiple unhealthy lifestyles might increase the risk of hyperuricemia, and this effect was stronger in participants with hypertension and dyslipidemia. Timely correction of unhealthy lifestyles, and control of hypertension and dyslipidemia might reduce the risk for hyperuricemia.
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Dislipidemias , Hipertensão , Hiperuricemia , Humanos , Hiperuricemia/epidemiologia , Estudos Transversais , Hipertensão/epidemiologia , Hipertensão/complicações , Fatores de Risco , Estilo de Vida , Dislipidemias/epidemiologia , Dislipidemias/complicações , PrevalênciaRESUMO
Bulk Bi0.5Sr0.5Fe0.5Cr0.5O3 (BSFCO) is a new compound comprising the R3c structure. The structural, magnetic property and exchange bias (EB) details are investigated. The material was in the super-paramagnetic (SP) state at room temperature. Exchange bias usually occurs at the boundary between different magnetic states after field cooling (HFC) acts on the sample. Here the result shows that changing HFC from 1 to 6 T reduces the HEB value by 16% at 2 K at the same time. Meanwhile, HEB diminishes as the ferromagnetic layer thickness increases. The variation of (the thickness of ferromagnetic layer) tFM with the change of HFC leads to the tuning of HEB by HFC in BSFCO bulk. These effects are obviously different from the phenomenon seen in other oxide types.
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Objective: To explore and establish the preparation system of human intestinal fluid transplantation (HIFT) and HIFT capsule, and to preliminarily apply it to clinic. Methods: Strict standards for donor screening and management were established. The nasojejunal tube was catheterized into the distal jejunum, and then it was connected with an improved disposable sterile negative pressure collection device for the collection of human intestinal fluid. After that, it was prepared into capsules by filtering, adding 10% glycerin protectant and freeze-drying method. The amount of living bacteria was used as the standard of therapeutic dose. The living bacteria amount in fluid is ≥ 5.0×108 /mL and the living bacteria proportion is ≥ 83%; the living bacteria amount in powder is ≥ 2.0×106 /g and the living bacteria proportion is ≥ 81%; The observational indicators included: (1) the basic information of the donor, the amount of living bacteria in the HIF and powder. (2) Preliminary analysis of the treatment for ASD, which combined HIFT capsule with standard FMT capsule, from February to December 2021 (Clinical trial Registration Number: ChiCTR2100043929). Evaluation criteria: Trypan blue staining method was used to detect the living bacteria amount in fluid and powder. The Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the efficacy. Results: Compared with the parent donor, the standard donor was younger [(25.4±0.9) y vs. (30.7±3.2) y, t=-19.097, P=0.001] and had a lower body mass index [(19.7±0.5) kg/m2 vs. (20.8±1.3) kg/m2, t=-8.726, P=0.001], more in the living bacteria amount in powder [(7.47±1.52)×106/g vs. (5.03±1.38)×106/g, t=11.331, P=0.031], Chao index (205.4±6.8 vs. 194.2±7.2, t=10.415, P=0.001), and Shannon index (3.25±0.14 vs 2.72±0.27, t=19.465, P=0.001). The differences were statistically significant (all P<0.05). However, there were no significant differences in gender, drainage volume and total number of bacterial liquid colonies between the two groups (all P>0.05). Both the standard donor and the parent donor met the donor screening criteria, and the preparation fluid and powder met the treatment criteria. Eight patients received the treatment of HIFT combined with fecal microbiota transplantation (FMT). Preliminary statistical results showed that HIFT combined with FMT improved ABC and CARS at the 1st, 2nd, 3rd and 4th months. The differences were statistically significant (all P<0.05). No severe adverse reaction occurred. Conclusion: Based on the previous research on FMT preparation system and the clinical technology in our center, this study developed a high standard HIFT preparation system, and explored the clinical study of HIFT combined with FMT, in order to provide an innovative therapy for the treatment of diseases.
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Glicerol , Azul Tripano , Bactérias , Criança , Transplante de Microbiota Fecal/métodos , Humanos , PósRESUMO
To screen lactic acid bacteria for starter cultures in cheese production, 21 Lactococcus strains previously isolated from natural fermented milk and koumiss made by herdsman families in the Xinjiang, Gansu, and Qinghai provinces of China were evaluated for optimal growth temperature, acidification activity, proteolytic activity, aminopeptidase activity, and autolytic activity. All isolates presented low acidification rates, and the pH value did not reach 5.3 after 6 h of inoculation in sterile reconstituted skim milk at 30°C. Strains X9C2 and T7C showed the highest proteolytic activity of 24.67 and 23.58 mg of glycine/L of milk, respectively. For aminopeptidase activity, strains X9C2 and T1C2 displayed the highest activities of 30.56 and 27.70 U/mg of protein using L-leucine-p-nitroanilide as substrate, respectively. Autolytic activity in simulated cheese-like buffer ranged from 7.45 to 34.76%, and strains Q14C2 and Q16C showed the highest values of 34.76 and 34.20%, respectively. Collectively, one main finding is that some technological characteristics of Lactococcus isolates from Chinese traditional fermented products varied greatly. Some isolates with potentially important properties could be valuable for application as starter cultures of cheese or could constitute a mixed culture.
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Produtos Fermentados do Leite/microbiologia , Microbiologia de Alimentos , Tecnologia de Alimentos , Lactococcus/metabolismo , Queijo/microbiologia , China , Manipulação de Alimentos , Ácido Láctico/biossíntese , Lactococcus/classificaçãoRESUMO
Brontispa longissima is one of the most serious insect pests of coconut in Southeast Asia; it was first discovered on Hainan Island in June 2002. Despite the economic risk associated with this pest, genetic aspects of the invasion process have remained relatively unexplored. Using microsatellite markers, we investigated the population structure, genetic variability and pattern of invasion in various geographic populations. The methodology was based on a modified biotin-capture method. Eight polymorphic microsatellite loci were isolated and characterized for the pest. The allele number per locus varied from 2 to 3 (N = 30). The expected and observed heterozygosities of the eight loci ranged from 0.042 to 0.509 and from 0.042 to 0.963, respectively. Although the frequency of polymorphisms was not very high in this population, the microsatellite loci that were isolated will be useful for investigating the genetic diversity and migration routes of B. longissima populations.
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Cocos/parasitologia , Besouros/genética , Besouros/patogenicidade , Repetições de Microssatélites/genética , Polimorfismo Genético/genética , Animais , Besouros/classificação , Variação Genética , HeterozigotoRESUMO
Ten microsatellite markers were isolated and characterized from Aleurodicus dispersus, the spiraling whitefly, an exotic pest species that is considered to be one of the most serious agricultural pests on Hainan Island, China. The polymorphism of these loci was examined in individual whiteflies from Hainan Island and from the Canary Islands. All loci were polymorphic, with two to four alleles per locus. Mean observed and expected heterozygosity values were 0.773 and 0.585, respectively. These microsatellite markers provide powerful tools for ecological, epidemiological and population genetic studies on this highly invasive insect. Thirty insects were collected and studied at each location. There were no differences between the two locations.
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Alelos , Loci Gênicos , Hemípteros/genética , Repetições de Microssatélites/genética , Polimorfismo Genético , AnimaisAssuntos
Anfetamina/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Locomoção/efeitos dos fármacos , Anfetamina/antagonistas & inibidores , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/antagonistas & inibidores , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Drosophila , Metanfetamina/farmacologia , Mutação , Peptídeos/farmacologia , Fosforilação/efeitos dos fármacosRESUMO
A subset of glutamate receptors that are specifically sensitive to the glutamate analog N-methyl-D-aspartate (NMDA) are molecular coincidence detectors, necessary for activity-dependent processes of neurodevelopment and in sensory and cognitive functions. The activity of these receptors is modulated by the endogenous amino acid D-serine, but the extent to which D-serine is necessary for the normal development and function of the mammalian nervous system was previously unknown. Decreased signaling at NMDA receptors has been implicated in the pathophysiology of schizophrenia based on pharmacological evidence, and several human genes related to D-serine metabolism and glutamatergic neurotransmission have been implicated in the etiology of schizophrenia. Here we show that genetically modified mice lacking the ability to produce D-serine endogenously have profoundly altered glutamatergic neurotransmission, and relatively subtle but significant behavioral abnormalities that reflect hyperactivity and impaired spatial memory, and that are consistent with elevated anxiety.