Calcium/calmodulin-dependent protein kinase II is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rat nucleus accumbens

Background@#Synaptic plasticity contributes to nociceptive signal transmission and modulation, with calcium/ calmodulin-dependent protein kinase II (CaMK II) playing a fundamental role in neural plasticity. This research was conducted to investigate the role of CaMK II in the transmission and regulation of nociceptive information within the nucleus accumbens (NAc) of naïve and morphine-tolerant rats. @*Methods@#Randall Selitto and hot-plate tests were utilized to measure the hindpaw withdrawal latencies (HWLs) in response to noxious mechanical and thermal stimuli. To induce chronic morphine tolerance, rats received intraperitoneal morphine injection twice per day for seven days. CaMK II expression and activity were assessed using western blotting. @*Results@#Intra-NAc microinjection of autocamtide-2-related inhibitory peptide (AIP) induced an increase in HWLs in naïve rats in response to noxious thermal and mechanical stimuli. Moreover, the expression of the phosphorylated CaMK II (p-CaMK II) was significantly decreased as determined by western blotting. Chronic intraperitoneal injection of morphine resulted in significant morphine tolerance in rats on Day 7, and an increase of p-CaMK II expression in NAc in morphine-tolerant rats was observed. Furthermore, intra-NAc administration of AIP elicited significant antinociceptive responses in morphine-tolerant rats. In addition, compared with naïve rats, AIP induced stronger thermal antinociceptive effects of the same dose in rats exhibiting morphine tolerance. @*Conclusions@#This study shows that CaMK II in the NAc is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rats.

Enhanced nitrogen removal by bioelectrochemical coupling anammox and characteristics of microbial communities / 生物工程学报

To investigate the bioelectrochemical enhanced anaerobic ammonia oxidation (anammox) nitrogen removal process, a bioelectrochemical system with coupled anammox cathode was constructed using a dual-chamber microbial electrolysis cell (MEC). Specifically, a dark incubation batch experiment was conducted at 30 ℃ with different influent total nitrogen concentrations under an applied voltage of 0.2 V, and the enhanced denitrification mechanism was investigated by combining various characterization methods such as cyclic voltammetry, electrochemical impedance spectroscopy and high-throughput sequencing methods. The results showed that the total nitrogen removal rates of 96.9%±0.3%, 97.3%±0.4% and 99.0%±0.3% were obtained when the initial total nitrogen concentration was 200, 300 and 400 mg/L, respectively. In addition, the cathode electrode biofilm showed good electrochemical activity. High-throughput sequencing results showed that the applied voltage enriched other denitrifying functional groups, including Denitratisoma, Limnobacter, and ammonia oxidizing bacteria SM1A02 and Anaerolineaceae, Nitrosomonas europaea and Nitrospira, besides the anammox bacteria. These electrochemically active microorganisms comprised of ammonium oxidizing exoelectrogens (AOE) and denitrifying electrotrophs (DNE). Together with anammox bacteria Candidatus Brocadia, they constituted the microbial community structure of denitrification system. Enhanced direct interspecies electron transfer between AOE and DNE was the fundamental reason for the further improvement of the total nitrogen removal rate of the system.

Antiproliferative effects of isoalantolactone in human liver cancer cells are mediated through caspase-dependent apoptosis, ROS generation, suppression of cell migration and invasion and targeting Ras/Raf/MEK signalling pathway.

The main objective of this study was to evaluate the in vitro antiproliferative effects of isoalantolactone against liver cancer cells (Hep-G2) and also monitor its mechanism of action. The MTT assay was involved in proliferation assessments and phase contrast microscopy was used to check cellular morphology. Acridine orange/ethidium bromide staining along with western blotting was used to evaluate proapoptotic effects of isoalantolactone. DCFH-DA staining was used in ROS measurements. Transwell migration and invasion assay were executed to check the effects of isoalantolactone on migration and invasion of Hep-G2 cells. Western blotting was used to check the expressions of Ras/Raf/MEK signalling pathway in Hep-G2 cells. Results demonstrated that isoalantolactone significantly (*p<0.05 and **p<0.01) inhibited the proliferation of Hep-G2 cells in a concentration and time-reliant fashion. The IC50 value of the tested isoalantolactone molecule was found to be 71.2 µM and 53.4 µM at 12 h and 24 h time intervals respectively. Moreover, the antiproliferative effects of isoalantolactone were mediated through induction of caspase-dependent apoptosis and oxidative stress (ROS mediated). The proapoptotic effects of isoalantolactone were evident from morphological assessments and improved expressions of caspase-3, -8, and -9 and Bax while antiapoptotic Bcl-2 was reduced significantly. Additionally, antiproliferative and proapoptotic effects of isoalantolactone were found to be a consequence of blocking of Ras/Raf/MEK signalling in Hep-G2 cells. Furthermore, isoalantolactone significantly (*p<0.05) targeted the migration and invasion of Hep-G2 cells. In conclusion, these results validated that isoalantolactone shows strong antiproliferative activity against Hep-G2 liver cancer cells. Therefore, it could prove as a leading candidate in liver cancer research, drug discovery and design.

Analysis and clinical significance of cytochrome P 450 2C19 gene in patients with cardiovascular and cerebrovascular diseases in southern Yunnan / 中国基层医药

Objective:To analyze the distribution and clinical significance of cytochrome P 450 2C19 (CYP2C19) gene in patients with cardiovascular and cerebrovascular diseases in southern Yunnan. Methods:The data of 245 patients with cardiovascular and cerebrovascular diseases who received treatment in Southern Central Hospital of Yunnan Province between May 2019 and June 2020 were retrospectively analyzed. The distribution of CYP2C19 gene and its relationship with nationality, age, sex, blood lipids, hypertension, and diabetes were analyzed and compared between southern Yunnan and other regions.Results:The proportions of seven phenotypes of CYP2C19 gene *1/*17, *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, *3/*3 in 245 patients were 2.86%, 38.37%, 39.18%, 5.31%, 9.39%, 4.08% and 0.82%, respectively. The proportions of individuals with superfast/ultrafast metabolism, fast metabolism, intermediate metabolism, and slow metabolism in 245 patients were 2.86%, 38.37%, 44.49%, and 14.29%, respectively. The frequency of polymorphisms in the CYP2C19 gene was consistent with the Hardy-Weinberg equilibrium ( P > 0.05), which was constant and representative. The Fisher test showed that the CYP2C19 gene distribution of patients with cardiovascular and cerebrovascular diseases in southern Yunnan was not greatly correlated with nationality, age, sex, underlying disease, blood lipids, and the types of cardiovascular and cerebrovascular diseases (all P > 0.05). There was a significant difference in CYP2C19 gene distribution in patients from southern Yunnan versus Dongguan, Jiangxi, Fujian, northern Sichuan, Chifeng, Xiamen, Shaanxi, and Kunming ( P < 0.001, < 0.001, 0.045, 0.008, 0.001, 0.005, < 0.001, 0.016). Conclusion:The distribution of CYP2C19 gene in patients with cardiovascular and cerebrovascular diseases in southern Yunnan is not obviously correlated with nationality, age, sex, underlying diseases, blood lipids, and the types of cardiovascular and cerebrovascular diseases. CYP2C19 gene distribution is related to regional distribution, which can guide personalized medication in different regions.

Leiomyomatosis peritonealis disseminata during pregnancy: a case report and literature review / 中华围产医学杂志

Objective:To review the clinical and pathological features, pathogenesis, and differential diagnosis of leiomyomatosis peritonealis disseminata (LPD) during pregnancy.Methods:We report the diagnosis and treatment of LPD in a pregnant woman admitted to Jiaozhou Central Hospital of Qingdao. We retrieved relevant literature from China and abroad to review the clinical characteristics and outcomes.Results:(1) Case report: The 33-year-old pregnant woman who had had previous cesarean sections was admitted at 37 +2 weeks gestation due to premature rupture of membranes 30 minutes before arriving at the hospital with a pelvic mass which was first diagnosed seven months earlier, in the first trimester. A lower segment cesarean section was performed, and the pelvic mass was removed on admission. No relapse was reported during the postoperative follow-up for 26 months. (2) Literature review: thirteen papers involving 15 cases, including the present case, were retrieved. The age at onset was 32 years old (19-47 years old); five of them had a history of myomectomy. Twelve cases had no significant symptoms, and the diagnosis was made at delivery or postpartum; the other three had noticeable features, mainly with abdominal pain. Six had obstetrical complications, including hypertensive disorders of pregnancy, premature rupture of membrane, abnormal fetal position, and oligohydramnios. Two cases had a history of assisted reproductive technology. Eleven cases delivered after 32 gestational weeks, three before 28 weeks, one aborted at ten gestational weeks due to severe complications. Twelve had cesarean section and myomectomy and the uterus and appendages were preserved. Three cases had a cesarean hysterectomy and two of them also had bilateral salpingo-oophorectomy. The pathological manifestations of seven cases were extensive and massively distributed small fibroids, similar to malignant tumor infiltration, with the diameter of 0.5 to 1.0 cm; five cases had multiple large fibroids, accompanied by scattered small fibroids. Conclusion:LPD during pregnancy is rare, and usually benign, with no obvious clinical symptoms. LPD is more likely to be misdiagnosed as a malignant tumor before the operation, and the diagnosis is usually confirmed by postoperative histopathology. A common surgical strategy is a cesarean section combined with pelvic mass resection.

Characteristics and risk factor analysis of femoral supracondylar fractures combined with meniscal and?ligamentous knee?injuries / 中华创伤杂志

Objective:To analyze the characteristics and related risk factors of femoral supracondylar fractures combined with meniscus and ligament injuries.Methods:A retrospective case series analysis was performed on clinical data of 100 patients with femoral supracondylar fractures combined with ipsilateral meniscal and?ligamentous knee?injuries?admitted to Tianjin Hospital from January 2016 to December 2020. There were 55 males and 45 females，with age of 22-78 years［（38.5 ± 3.3）years］. Causes of injury included traffic accidents in 45 patients，falls in 45 and others in 10. According to AO classification，type A1 was in 56 patients，A2 in 33 and A3 in 11. Sixty of these patients presented fractures on the left side and forty on the right side. All patients accepted MRI examination to estimate meniscal and ligamentous knee injuries concerning its prevalence，locations and severity. Locations of injury included the medial meniscus（MM），lateral meniscus（LM），anterior cruciate ligament（ACL），posterior cruciate ligament（PCL），medial collateral ligament（MCL）and lateral collateral ligament（LCL）. Meniscal knee injuries were measured using Stoller four-level method，and ligamentous knee injuries by Ruiz three-level method. The patients were subdivided based on age，sex，causes of injury，injury side and fracture AO classification to measure the prevalence of meniscal and?ligamentous injuries，and to identify the factors related to injuries using logistic regression analysis.Results:Seventy-six patients（76.0%）were complicated with meniscal or ligamentous injuries in 151 different parts. Twenty-nine patients（29.0%）had both meniscal and ligamentous injuries. Fifty-six patients had meniscal injuries，including 11 with bilateral meniscus injuries. MM injuries were noted in 32 patients（32.0%），with severity of grade Ⅰ in 19 patients，grade Ⅱ in 12 and grade Ⅲ in 1. LM injuries were found in 35 patients（35.0%），with severity of grade Ⅰ in 19 patients，grade Ⅱ in 14 and grade Ⅲ in 2. Forty-nine patients had ligamentous injuries，among which 22 patients were with single ligamentous injuries，19 with double ligamentous injuries and 8 with triple ligamentous injuries. ACL injuries were found in 33 patients（33.0%），with severity of grade Ⅰ in 22 patients，grade Ⅱ in 10 and grade Ⅲ in 1. PCL injuries occurred in 4 patients（4.0%），with severity of grade Ⅰ in 3 patients and grade Ⅱ in 1. MCL injuries occurred in 28 patients（28.0%），with severity of grade Ⅰ in 18 patients，grade Ⅱ in 9 and grade Ⅲ in 1. LCL injuries occurred in 19 patients，with severity of grade Ⅰ in 12 patients，grade Ⅱ in 5 and grade Ⅲ in 2. There were significant differences in prevalence of meniscal injuries among subgroups of different gender，causes of injury and fracture types（ P < 0.05）.Logistic regression analysis suggested that gender and fracture types showed significant correlation with meniscal injuries，especially factors of males（ P < 0.05）and type A3 fractures（ P < 0.01）. There were significant differences in prevalence of ligamentous injuries among subgroups of different causes of injury and fracture types（ P < 0.05）. Logistic regression analysis showed that causes of injury and fracture types were significantly related to ligamentous injuries，especially factors of traffic accidents（ P < 0.01）and type A3 fractures（ P < 0.01）. Conclusions:Ipsilateral meniscal or ligamentous knee injuries have a high incidence in patients with supracondylar femoral fractures. There exist multiple-site injuries，particularly in ligamentous injuries. Males，type A3 fractures and traffic injuries are risk factors，which needs to be paid much attention in clinical diagnosis and treatment.

Considerations on the chemistry, manufacture and control requirements for conditional marketing authorization drugs in China / 中国药科大学学报

@#Drug Administration Law revised in 2019 proposed for the first time conditional marketing authorization at the legal level, marking the formal implementation of the conditional marketing authorization in China. This paper compares the regulations and technical requirements of conditional marketing authorization drugs in China with those in Europe and the United States, in an attempt to learn from the experience of chemistry, manufacture and control review of these drugs in Europe and the United States, and to discuss the pharmaceutical technical requirements of conditional marketing authorization drugs in China.

CD137 signaling promotes angiogenesis through regulating macrophage M1/M2 polarization / 中华心血管病杂志

Objective: To investigate whether CD137 signaling can promote angiogenesis via regulating macrophage M1/M2 polarization. Methods: (1) The primary peritoneal macrophages in mice induced by 3% thiglycollate broth were divided into three groups: control group, CD137 signaling activated group and CD137 signaling inhibited group. Various specific markers of M1 and M2 macrophages were detected to observe the phenotype change of macrophages, and the macrophages protein expression of CD137, CD86 and CD206 was detected by flow cytometry (FCM). The protein and mRNA expression of induced nitric oxide synthase (iNOS), arginase Ⅰ(Arg-1) was determined by Western blot and RT-PCR, respectively. The secretion levels of IL-12 and IL-10 in culture supernatant of macrophages were detected by ELISA. (2) Macrophages were co-cultured with the endothelial cells (bEnd.3), and macrophages were implanted in the upper chamber, endothelial cells were implanted in stromal glue of the lower chamber. The experiment was divided into three groups: the control group, CD137 signaling activated group and peroxisome proliferator-activated receptor-γ (PPAR-γ) inhibited group, and tube formation ability of endothelial cells in each group was determined. Results: (1) The purity of primary peritoneal macrophages in mice was (97.93±1.31)%. The expression of CD137 on the surface of macrophages was (97.40±2.70)%. (2) Compared with control group, the mRNA and protein expression levels of Arg-1 were significantly increased and the mRNA and protein expression of iNOS were significantly decreased in CD137 signaling activated group (all P<0.05). Compared with CD137 signaling activated group, the mRNA and protein expression of Arg-1 were significantly lower and the mRNA and protein expression levels of iNOS were significantly higher in CD137 signaling inhibited group (all P<0.05). FCM results showed that the average fluorescence intensity of CD206 was higher, while the average fluorescence intensity of CD86 was lower in CD137 signaling activated group than in control group (P<0.05, P<0.01, respectively); the expression of CD206 was significantly lower, while the expression of CD86 was higher, in the CD137 signaling inhibited group than in CD137 signaling activated group (P<0.05, P<0.01, respectively). ELISA results showed that the secretion of IL-10 was higher, and the secretion level of IL-12 was significantly lower in CD137 signaling activated group than in control group (both P<0.01); the secretion of IL-10 was significantly lower and the secretion of IL-12 was significantly higher in CD137 signaling inhibited group than in CD137 signaling activated group (both P<0.05). (3) Values of the formation of tube length and branch number were both longer in CD137 signaling activated group than control group (P<0.05). The formation of the tube length and branch number were less in PPAR-γ inhibited group than in CD137 signaling activated group (P<0.05). Conclusion: CD137 signaling can promote angiogenesis by regulating macrophage M1/M2 polarization.

Thermal Performance of Two Indigenous Pupal Parasitoids Attacking the Invasive Drosophila suzukii (Diptera: Drosophilidae).

Pachycrepoideus vindemiae (Rondani) and Trichopria drosophilae (Perkins) are among a few indigenous parasitoids attacking the invasive Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) in North America. Both parasitoid species occur in California, whereas only P. vindemiae has been reported from Oregon. We compared the thermal performance of the California populations of P. vindemiae and T. drosophilae, and the Oregon population of P. vindemiae at eight constant temperatures (12.6-32.8°C). Both P. vindemiae populations could develop at all tested temperatures. T. drosophilae failed to develop at or above 29.6°C. This species was, however, able to develop at a diurnal temperature regime of 15-32°C, and survival was higher in older developmental stages. T. drosophilae was less tolerant to both low and high temperatures than P. vindemiae, whereas the Oregon P. vindemiae population was more cold-tolerant but less heat-tolerant than the California population in terms of offspring survival, development, and reproduction. To develop storage strategies for mass-cultured parasitoids, we compared the cold tolerance of immature P. vindemiae and T. drosophilae of the California populations at 12°C for 1, 2, or 3 mo, followed by a 23°C holding period. Successful development to the adult stage decreased as cold storage duration increased. Successful development, however, increased when cold storage was initiated during the older developmental stages for 1-mo exposure for both parasitoid species. The results are discussed with regards to parasitoid thermal adaptation and the potential use of P. vindemiae and T. drosophilae for biological control of spotted-wing drosophila.

Effects of Ketamine on Basal Gamma Band Oscillation and Sensory Gating in Prefrontal Cortex of Awake Rats / 神经科学通报·英文版

Gamma band oscillation (GBO) and sensory gating (SG) are associated with many cognitive functions. Ketamine induces deficits of GBO and SG in the prefrontal cortex (PFC). However, the time-courses of the effects of different doses of ketamine on GBO power and SG are poorly understood. Studies have indicated that GBO power and SG have a common substrate for their generation and abnormalities. In this study, we found that (1) ketamine administration increased GBO power in the PFC in rats differently in the low- and high-dose groups; (2) auditory SG was significantly lower than baseline in the 30 mg/kg and 60 mg/kg groups, but not in the 15 mg/kg and 120 mg/kg groups; and (3) changes in SG and basal GBO power were significantly correlated in awake rats. These results indicate a relationship between mechanisms underlying auditory SG and GBO power.

Progress of exosomes in tumor immune escape / 肿瘤研究与临床

Exosomes are a type of nanoscale vesicles that are actively secreted by various type of cells, and are considered as a new way of cell communication. The exosomes can shuttle bioactive molecules including proteins, lipids, miRNAs and mRNAs from one cell to another, resulting in the exchange of genetic information between cells and the reprogramming of recipient cells. Many evidences show that tumor cells can secrete a large amount of exosomes and regulate tumor progression,metastasis,immune escape, resistance and many other aspects through a variety of ways. In the tumor microenvironment, exosomes transmit between tumor cells,immune cells,and stromal cells,contributing to the escape from immune surveillance.This review summarizes recent advances in exosomes in tumor immune escape.

Linear functional response by two pupal Drosophila parasitoids foraging within single or multiple patch environments.

Functional response describes the number of prey or hosts attacked by a predator or parasitoid as a function of prey or host density. Using three different experimental designs, we found a linear functional response by two insect parasitoids (the pteromalid Pachycrepoideus vindemiae and the diapriid Trichopria drosophilae) to their hosts (the drosophilids Drosophila suzukii and D. melanogaster). A linear function response is considered unusual for insect parasitoids. The first design was a 'fixed time within patch experiment' where individual parasitoids were exposed to a range of host densities for 24 h; the second two designs were a 'variable time functional response' and a 'selective functional response' experiments where individual parasitoids were presented with a range of host patches and allowed to freely select and explore only one patch (variable time) or forage for 24 h (selective). In all experimental designs, the number of hosts parasitized increased linearly until reaching an upper limit. Under the laboratory conditions used, the functional response of P. vindemiae was limited by its egg supply and time (host handling time) whereas T. drosophilae was limited by time only. The linear functional response by both parasitoids likely resulted from a constant attack rate and an incremental foraging strategy where the parasitoids left a poor (low density) host patch or remained in a higher quality host patch when there was successful oviposition and adequate host density.

Expression of Toll-like receptor 2 in glioma and its correlation / 中国医师进修杂志

Objective To investigate the expression of Toll like receptor 2 (TLR2) in glioma and its relationship with the malignant biological behavior of glioma, so as to provide a new therapeutic target for glioma immunotherapy. Methods The tumor tissues of 90 glioma patients undergoing surgical excision were collected, of which WHO gradingⅠ-Ⅱgrade 39 cases,Ⅲgrade 24 cases,Ⅳgrade 24 cases. In addition, the normal brain tissues of 12 patients undergoing routine intracranial decompression were selected. The human glioma cell lines U87-MG, U251-MG and human astrocyte cell line HA were cultured. The expression levels of TLR2 mRNA and protein were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and Western Blot test. The correlation between TLR2 protein and different clinical pathological parameters was analyzed. Results The expression levels of TLR2 mRNA and protein in the glioma tissuesⅠ-Ⅱgrade,Ⅲgrade andⅣgrade were significantly higher than those in normal brain tissues (0.27 ± 0.09, 0.57 ± 0.12 and 0.96 ± 0.18 vs. 0.11 ± 0.05; 0.31 ± 0.05, 0.44 ± 0.05 and 0.71 ± 0.09 vs. 0.02 ± 0.01), there were statistical differences (P0.05), but was related to tumor diameter and WHO grading (P < 0.01). Conclusions TLR2 in different grade glioma tissues and glioma cell lines are expressed, and its expression level is associated with the malignant degree of glioma; TLR2 protein not only can be used as a biomarker of gliomas and prognosis, but also provide a new target for the treatment of glioma.

Overwintering Survival of Drosophila suzukii (Diptera: Drosophilidae) and the Effect of Food on Adult Survival in California's San Joaquin Valley.

The overwintering survival and development of Drosophila suzukii Matsumura were investigated in California's San Joaquin Valley. Drosophila suzukii were exposed to overwintering conditions in cages hung in a citrus orchard, and the pupae were buried in the soil. Eggs exposed from late November to January did not survive; a low percentage (<3%) of larvae and pupae developed into adults. Survival of pupae was significantly higher when buried in the soil than on the citrus tree. From late January to March, all life stages developed into adults and overwintered adult female D. suzukii produced eggs when provided with 10% honey-water and sliced oranges. Adult survival varied among fruit juice provision treatments and overwintering exposure periods, ranging from 3.4 ± 0.9 d (water) to 44.1 ± 3.0 d (10% honey-water). Fruit juices of apple, cherry, grape, orange, and pomegranate were tested as adult food sources; results showed that adult female and male D. suzukii lived only 2 d with water only, whereas adults survived from 14.2 to 34.8 d with fruit juice treatments and the 10% honey-water control. An unexpected event was the oviposition and immature development of D. suzukii with the fruit juice. In a follow-up laboratory trial, when 10% honey-water or orange juice were provided along with an artificial diet for oviposition and immature development, female D. suzukii survived for 21.6 ± 2.4 or 21.6 ± 1.5 d, and produced 106.8 ± 14.1 or 98.5 ± 13.1 offspring, respectively. We discuss factors potentially influencing overwintering survival of D. suzukii.

Leachables in metered-dose inhaler packages:research advances / 国际药学研究杂志

The container closure system is indispensable to metered-dose inhaler(MDI). In the shelf life of MDI,various in?gredients of the container closure system may become potential leachables and migrate into the preparation. Due to their unknown con?structs and latent ambiguous toxicities,leachables may significantly affect drugs′effectiveness and safety. Consequently,it is neces?sary to carry on leachable studies to ensure the good compatibility of MDI closure system. This paper mainly focuses on the fundamen?tal components of MDI container closure system,analyzes leachable sources and safety information and reviews the related contents about leachable studies in domestic and foreign pharmacopoeia.

Determination of Related Substances of Bifonazole Raw Material by HPLC / 中国药房

OBJECTIVE:To establish a method for the determination of related substances in bifonazole raw material. METH-ODS:HPLC method was performed on the column of Kromasil C18 with mobile phase of methanol-0.02 mol/L phosphoric acid(ad-justed pH to 7.5 with triethylamine)(70:30,V/V)at a flow rate of 1.0 ml/min,detection wavelength was 258 nm,volume injection was 20 μl,and the column temperature was 40 ℃. RESULTS:The linear range was 0.05-0.25 μg/ml for bifonazole(r=0.9996), 0.05-0.25 μg/ml for impurity A(bifonol)(r=0.9997)and 0.05-0.25 μg/ml for impurity B(4-C isomer)(r=0.9995);the detec-tion limits were 8.2 ng/ml,7.5 ng/ml and 8.4 ng/ml,and the quantification limits were 27.1 ng/ml,24.7 ng/ml and 27.8 ng/ml,re-spectively;RSDs of precision and reproducibility tests were lower than 1%;recovery of impurity B was 95.13%-101.29%(RSD=1.89%,n=9);both impurity A and impurity B were were detected in the 3 batches of samples. CONCLUSIONS:The method is accurate,sensitive and reproducible,and can be used for the determination of the related substances in bifonazole raw material.

Leachables in metered-dose inhaler packages: Research advances / 国际药学研究杂志

The container closure system is indispensable to metered-dose inhaler (MDI). In the shelf life of MDI, various ingredients of the container closure system may become potential leachables and migrate into the preparation. Due to their unknown constructs and latent ambiguous toxicities, leachables may significantly affect drugs’ effectiveness and safety. Consequently, it is necessary to carry on leachable studies to ensure the good compatibility of MDI closure system. This paper mainly focuses on the fundamental components of MDI container closure system, analyzes leachable sources and safety information and reviews the related contents about leachable studies in domestic and foreign pharmacopoeia.

Determination of Chloride and Sulfate in Lithium Carbonate Crude Drug by Ion Chromatography / 中国药师

Objective:To establish a method for the determination of chloride and sulfate in lithium carbonate crude drug by sup-pressed ion chromatography. Methods:The analysis column and the guard column was Thermo IonPac AS11(250 mm × 4 mm) and IonPac AG 11(50 mm ×4 mm), respectively. Potassium hydroxide solution(10 mmol·L-1) generated by an eluent generator(EG) was used as the eluent at a flow rate of 1. 0 ml·min-1 . And the temperature of column and conductivity cell was 30℃ and 35℃, re-spectively. The suppressor electric current was 36 mA, and the injection volume was 10 μl. Results:The linear range of chloride ion and sulfate ion was 1. 0-20μg·ml-1 with r of 0. 995 1 and 0. 997 3,respectively, and the recovery was 106. 6%(RSD=2. 6%,n=6) and 100. 3%(RSD=1. 9%,n=6), respectively. Conclusion:The method is accurate and reliable, and can be used in the determina-tion of chloride and sulfate in lithium carbonate crude drug.

Tri-trophic movement of carotenoid pigments from host plant to the parasitoid of a caterpillar.

Insect parasitoids normally produce white colored eggs. Habrobracon gelechiae (Hymenoptera: Braconidae) is a gregarious ectoparasitoid of various caterpillars. We found that adult female H. gelechiae lays yellow colored eggs when its larvae developed from host larvae of Choristoneura rosaceana and Epiphyas postvittana (both Lepidoptera: Tortricidae) that were fed green plant leaves, but white colored eggs when these same host larvae species were fed non-plant diets. This study investigated the causes of egg color in H. gelechiae and the possible consequences in terms of parasitoid fitness resulting from differential egg color. Using high-performance liquid chromatography we demonstrated that the yellow coloration resulted from the uptake of carotenoid plant pigments (mainly lutein and ß-carotene) that were initially ingested by the caterpillar larvae from plant leaves, later absorbed by the parasitoid larvae (F0) feeding on the host and carried over to the adult parasitoids, and finally translocated to the eggs (F1) of the parasitoids. The amount of plant pigments consumed by the parasitoid larvae (F0) affected the intensity of the yellow color of the parasitoid's eggs (F1). Similarly, egg color was affected by the adult female parasitoids lifetime egg production and deposition rate. Further tests suggest that the observed differences in egg color did not have a genetic basis and did not affect egg viability or fitness. To our best knowledge, this is the first report of a tri-trophic and multi-stage translocation of carotenoid plant pigments in parasitoids. We discuss possible evolutionary significance and putative functions of the absorption of plant pigments by parasitoid species.

Factors Limiting Peach as a Potential Host for Drosophila suzukii (Diptera: Drosophilidae).

The spotted wing drosophila, Drosophila suzukii Matsumura, has widely established in North America and become an economic concern for a variety of fruit crops. To better understand fruit susceptibility, we evaluated peach surface characteristics on the pest's oviposition success. The number of D. suzukii eggs laid into the fruit flesh was tested on 1) peaches with or without indumenta (commonly referred to as peach fuzz), 2) peaches physically damaged by harvest operations, 3) peaches damaged by the peach twig borer Anarsia lineatella Zeller or the forktailed bush katydid, Scudderia furcata Brunner von Wattenwyl, and 4) peaches with punctures that simulated stink bug damage. Female D. suzukii did not lay eggs in intact fuzzy sections of the fruit or into small punctures (0.3 or 0.5 mm), but readily laid eggs in sections without fuzz, with insect damage, and with large punctures (1 mm). The number of eggs per treatment was positively related to the area of the damaged section; the overall fruit firmness and sugar content was not related to the number of eggs laid in treated or damaged spots. Direct observations of D. suzukii oviposition confirmed that peach fuzz appeared to be an obstacle for the fly's oviposition success, and female flies ceased ovipositional attempts on fuzzy peach sections after a short period of time. Successful oviposition times were associated with substrate firmness, with shorter oviposition time in damaged spots than in cherry fruit or shaved spots of the peach. The results indicate that intact, preharvest peach fruit are unlikely to be infested by the fly, but any surface damage could render the fruit susceptible to the fly.