OBJECTIVE: To study the pharmacokinetics of risperidone (RIS) nasal gel and its brain targeting effect and related mechanisms in rats. METHODS: The concentrations of RIS in rat plasma and brain tissues were determined by HPLC method. The pharmacokinetics and relative bioavailability to oral RIS preparation of RIS nasal gel and the drug distribution in various brain tissues such as olfactory bulb (OB), olfactory tract (OT), cerebellum (CL) and cerebrum (CR) were investigated in rats. RESULTS: The main pharmacokinetic parameters of RIS following nasal and oral administration such as tmax and ρmax were 5 and 20 min, 9.89 and 1.93 μg·mL-1, respectively. The relative bioavailability of nasally administered RIS was up to 4 730%. Furthermore, the AUC values of RIS nasal gel for different brain tissues such as OB, OT, CL and CR were found to be 45.3, 9.9, 1.5 and 1.1 folds of those of oral drug suspension, respectively. CONCLUSION: The in vivo absorption rate and bioavailability of RIS following nasal administration are obviously increased and improved. Additionally, the significant brain targeting characteristics of the drug nasal gel is also confirmed.

OBJECTIVE: To prepare a nasal gel of risperidone (RIS) and evaluate its in vitro quality. METHODS: The formulation and preparation process of RIS nasal gel were optimized with orthogonal test using appearance,spreading ability and in vitro release as main evaluation indexes. The quality items of the optimized RIS nasal gel such as appearance,pH value,contents of RIS and preservative,in vitro release and related substances were then evaluated. RESULTS: The optimal formulation of the RIS nasal gel consisted of 0.5% RIS, 0.35% carbopol 940, 0.5% chlorobutanol,20% propanediol and 15% DM-β-CD and appropriate amount of purified water. Its ideal pH value was about 6.0. Furthermore,the quality items such as the appearance,pH value,contents of RIS and preservative,in vitrorelease and related substances of the preparation all conformed to the relevant quality requirements in China Pharmacopiea (2010). CONCLUSION: The RIS nasal gel will be a promising new preparation for nasal administration due to its reasonable formulation,simple preparation process and controllable quality.

AIMTo investigate the complexation of prostaglandin E1 (PGE1) with hydroxylpropyl-beta-cyclodextrin (HP-beta-CD) in aqueous solutions, inclusion molar ratio of the host and guest molecules and change of thermodynamic parameters during the complexation process.

METHODSThe measurements of the complexation mechanism, inclusion molar ratio of the host and guest molecules and change of thermodynamic parameters were carried out by the following methods separately: phase solubility method, UV absorption spectroscopy, circular dichroism spectroscopy, equimolar series method and thermodynamic method, respectively.

RESULTSThat all the phase solubility diagrams showed a typical AL-type in various pH buffered solutions, suggested the formation of a soluble complex of 1:1 molar ratio. Both UV absorption spectroscopy and circular dichroism spectroscopy confirmed that the significant interaction between the host and guest molecules was probably due to the inclusion of chromophore moiety of PGE1 molecule into the hydrophobic cavity of HP-beta-CD molecule. The change in the thermodynamic parameters suggested that the complexation could proceed spontaneously along with the release of heat and the decrease of entropy.

CONCLUSIONAn 1:1 molar ratio inclusion complex of PGE1 with HP-beta-CD could be formed spontaneously and, hence, the solubility of PGE1 in aqueous solution increased. Appropriate temperature and suitable media pH probably favor the progress of complexation procedure.

2-Hydroxypropyl-beta-cyclodextrin ; Alprostadil ; administration & dosage ; chemistry ; Hydrogen-Ion Concentration ; Solubility ; Technology, Pharmaceutical ; methods ; Temperature ; beta-Cyclodextrins ; administration & dosage ; chemistry

The pharmacodynamics of prostaglandin E1 (PGE1) administered by different routes to rats was investigated in this paper. The hypotensive effect of PGE, was used as an index of drug efficacy, pharmacodynamic parameters such as time to reach peak effect (Tmax), maximal percentage of blood pressure decrease (Emax, %), duration of effect (Td), and the area under the blood pressure decrease percent-time curves (AUC, % x min) were determined after PGE1 given to rats intranasally, sublingually, intraperitoneally (ip), and intramuscularly (im), separately, and compared with those obtained from intravenous (iv) administration. Similar to iv route, the pharmacodynamic parameters of PGE1 from the other administration routes, Emax, Td and in particular AUC values were all increased with increasing doses, showing dose-efficacy relationship. Tmax was found to be approximately 3-4 min for nasal route, 3-8 min for im, 6-8 min for ip and 12-30 min for sublingual route, separately. Thus, the order of magnitude of absorption rate of the drug was as follows: nasal approximately = im > ip > sublingual. If the pharmacological bioavailability (PF) for each administration route was used as a tentative measure of drug absorption extent, the order of magnitude of absolute bioavailability appeared as follows: nasal > im approximately = ip > sublingual. Furthermore, the interindividual difference was found to be larger for im and ip route than that for nasal and sublingual route. These results indicate nasal and sublingual routes are two promising routes for the systemic delivery of PGE1 in clinical applications.
Administration, Intranasal ; Administration, Sublingual ; Alprostadil ; administration & dosage ; pharmacokinetics ; pharmacology ; Animals ; Area Under Curve ; Biological Availability ; Blood Pressure ; drug effects ; Dose-Response Relationship, Drug ; Injections, Intramuscular ; Injections, Intraperitoneal ; Injections, Intravenous ; Male ; Rats ; Rats, Wistar

Objective To investigate the influencing factors of epileptic seizure in chronic renal failure (CRF) patients.Methods CRF patients,admitted to our hospital from March 2014 to October 2018,were chosen in our study,and divided into epilepsy group (n=40) and non-epilepsy group (n=3653) according to whether the patients were with or without epilepsy.Clinical data,as length of hospital stays,dialysis methods,presences of infection,sites of infection,and use of antibiotics,and laboratory variables,as blood routine examination,straw aminotransferase (AST),and alanine aminotransferase (ALT),were collected and retrospectively analyzed.Logistic regression analysis was used to determine the independent factors affecting seizures in patients with CRF.Results The patients in the epilepsy group had significantly longer duration of dialysis and length of hospital stays,statistically higher incidence of infection and proportion of dialysis,and significantly worse prognosis than the patients from non-epilepsy group (P＜0.05).The leukocyte count of the epilepsy group was significantly higher than that of the non-epilepsy group,the contents of hemoglobin,ALT and albumin were significantly lower than those of the non-epilepsy group,and the contents of urea nitrogen,creatinine and serum potassium were significantly higher than those of the non-epilepsy group (P＜0.05).Logistic regression analysis showed that epilepsy was associated with serum potassium,creatinine,urea nitrogen and dialysis.Conclusion The etiology of epilepsy is complex,which is related to dialysis,toxin levels,and electrolyte imbalance;the mortality rate of those patients is high and the prognosis is not good.

Callicarpa nudiflora,which is a big brand of Li nationality medicine with Hainan characteristics,has the effects of dissolving stasis,hemostasis,anti-inflammatory and antibacterial. At present,there is a lack of information about the reference genome of C. nudiflora. The study of the genome size,heterozygosity rate and characteristics of SSR of C. nudiflora,can provide an effective basis for the formulation of the whole genome de novo sequencing strategy and development of SSR molecular markers of C. nudiflora. To realize this purpose,high throughput sequencing platform Illumina Hiseq was used to sequence the genome structure of C. nudiflora and K-mer analysis was applied to estimate genome size,repeat sequences and heterozygosity rate. Simple-sequence repeat( SSR) loci that are suitable as markers were identified by MISA software. The results showed the estimated genome size of C. nudiflora was 822. 43 Mb,with a 0. 85% heterozygosity rate and 71. 67% repeats,and the GC content of genome was about 49. 20%. Therefore,C. nudiflora belongs to a complex genome with high heterozygosity and repetition. SSR molecular genetic markers were analyzed in the genome sequence,and a total of 206 049 SSRs were identified,among which mono-nucleotide,di-nucleotide and tri-nucleotide repetitive motifs summed up to 198 993,accounting for 96. 57% of the total SSRs. Among the 2-6 nucleotide repeats,AT/AT,AAT/ATT,AGCC/CTGG,AAAAT/ATTTT and AGATAT/ATATCT have the largest number,respectively. This report represents the first genome-wide characterization of C. nudiflora,and provides a reference for the construction of the library for the fine sequencing of the genome,and a molecular basis for the development of SSR molecular markers as well as for the protection and utilization of gene resources.
Callicarpa/genetics* ; Genetic Markers ; Genome, Plant ; Microsatellite Repeats ; Polymorphism, Genetic

Objective:To investigate the epidemiological and clinical characteristics of human parainfluenza viruses (HPIVs) infection among hospitalized children with community-acquired pneumonia (CAP) in China, and provide basic data for diagnosis, treatment and prevention of HPIVs infection.Methods:From November 2014 to February 2020, 5 448 hospitalized children with CAP were enrolled in 14 hospitals in 11 provinces and municipalities directly under the Central Government in southern China and northern China. Nasopharyngeal aspirates or throat swabs were collected, and the nucleic acids of 18 types respiratory viruses including HPIV1-4 were screened by suspension array technology. Demographic data and clinical information were collected for statistical analysis.Results:The total detection rate of HPIVs in 5 448 children with CAP was 8.83% (481/5 448), and the detection rate in males was higher than that in females (62.79% vs. 37.21%; χ2=0.000, P=0.992). The detection rate of HPIVs in 1~< 3 years age group was higher than that in other age groups, and the difference was statistically significant ( χ2=61.893, P<0.001). The detection rate of HPIVs in the northern region was higher than that in the southern region (9.02% vs 8.65%), but the difference was not statistically significant ( χ2=0.239, P=0.625). The prevalence of HPIV1-4 in northern and southern China was not completely same. HPIV1 was mainly prevalent in autumn in both northern and southern regions. HPIV2 was prevalent in summer in northern China, and the detection rate was low in southern China. HPIV3 reached its peak in both spring and summer in both northern and southern China, but its duration was longer in southern China than in northern China. HPIV4 is mainly popular in autumn in both southern China and northern China. Among 481 children infected with HPIVs, 58.42% (281/481) were infected with HPIV alone, and the main clinical manifestations were cough (90.75%) and fever (68.68%). Out of the HPIV-positive cases, 42.62% (205/481) were co-infected with another type of HPIV or a different virus, while 11.43% (55/481) had co-infections with two or more different viruses. HPIV3 was the most common type of co-infection with other viruses. HPIV3 infection accounted for the largest proportion (76.80%) in 47 HPIVs-positive children with severe pneumonia. Conclusions:HPIVs is one of the most important pathogens causing CAP in children in China, and children under 3 years of age are the main populations of HPIVs infection. The prevalence characteristics of all types of HPIVs in children in the north and south are not completely same. HPIV3 is the dominant type of HPIV infections and causes more severe diseases.

In this study, we aimed to evaluate the toxic effects, changes in life span, and expression of various metabolism-related genes in Caenorhabditis elegans, using RNA interference (RNAi) and mutant strains, after 3-bromopyruvate (3-BrPA) treatment. C. elegans was treated with various concentrations of 3-BrPA on nematode growth medium (NGM) plates, and their survival was monitored every 24 h. The expression of genes related to metabolism was measured by the real-time fluorescent quantitative polymerase chain reaction (qPCR). Nematode survival in the presence of 3-BrPA was also studied after silencing three hexokinase (HK) genes. The average life span of C. elegans cultured on NGM with 3-BrPA was shortened to 5.7 d compared with 7.7 d in the control group. hxk-1, hxk-2, and hxk-3 were overexpressed after the treatment with 3-BrPA. After successfully interfering hxk-1, hxk-2, and hxk-3, the 50% lethal concentration (LC₅₀) of all mutant nematodes decreased with 3-BrPA treatment for 24 h compared with that of the control. All the cyp35 genes tested were overexpressed, except cyp-35B3. The induction of cyp-35A1 expression was most obvious. The LC₅₀ values of the mutant strains cyp-35A1, cyp-35A2, cyp-35A4, cyp-35B3, and cyp-35C1 were lower than that of the control. Thus, the toxicity of 3-BrPA is closely related to its effect on hexokinase metabolism in nematodes, and the cyp-35 family plays a key role in the metabolism of 3-BrPA.
Animals ; Caenorhabditis elegans/metabolism* ; Caenorhabditis elegans Proteins/genetics* ; Cytochrome P-450 Enzyme System/genetics* ; Hexokinase/physiology* ; Pyruvates/toxicity* ; RNA, Messenger/analysis*