Procaine, lidocaine, and ketamine inhibit histamine-induced contracture of guinea pig tracheal muscle in vitro

In vitro experiments using guinea pig tracheal smooth muscle were performed to compare the relaxant properties of procaine, lidocaine, and ketamine following contracture induced by histamine. Procaine produced a spasmolytic effect in a dose-related manner. In the doses tested, relaxation induced by procaine was more pronounced than that produced by either lidocaine or ketamine, although the latter 2 drugs also had a significant spasmolytic effect.     

Combined VSV oncolytic virus and chemotherapy for squamous cell carcinoma

OBJECTIVES: Vesicular stomatitis virus (VSV) is a negative-strand ribonucleic acid (RNA) virus that replicates specifically in tumor cells and has oncolytic effects in a variety of malignant tumors. We previously demonstrated recombinant VSV vectors incorporating viral fusion protein (rVSV-F) and interleukin 12 (rVSV-IL12) to have significant antitumor effects against squamous cell carcinoma (SCC) in a murine model. Here we evaluate the potential to combine a potent chemotherapeutic agent for SCC (cisplatin) with rVSV-F and rVSV-IL12 to improve efficacy. STUDY DESIGN: In vitro, three SCC cell lines were tested using rVSV-F and rVSV-IL12 with cisplatin, monitoring viral replication and cell survival. In an orthotopic floor of mouth murine SCC model, intratumoral injections of virus combined with systemic cisplatin were tested for tumor control and animal survival. RESULTS: In vitro, virus and cisplatin combination demonstrated rapid replication and enhanced tumor cell kill. Human keratinocytes were unaffected by virus and cisplatin. In vivo, combined rVSV-F with cisplatin reduced tumor burden and improved survival (P = .2 for both), while rVSV-IL12 monotherapy had better tumor control (P = .06) and survival (P = .024) than combination therapy. CONCLUSIONS: Addition of cisplatin did not affect the ability of either virus to replicate in or kill murine SCC cells in vitro. In vivo, combination therapy enhancedrVSV-F antitumor activity, but diminished rVSV-IL12 antitumor activity. Combination therapy may provide useful treatment for SCC with the development of more efficient viral vectors in combination with different chemotherapy agents or immunostimulatory agents.     

缬沙坦与安体舒通联合治疗对原发性高血压心肌细胞外基质重塑的影响

目的　研究缬沙坦与安体舒通联合治疗对原发性高血压 (EH)心肌细胞外基质重塑的影响。方法　选择 76例EH患者 ,随机分为两组 :X组 ,缬沙坦 80mg/d ,X A组 ,缬沙坦 80mg/d加安体舒通 2 0mg/d ,疗程 6月 ,应用放射免疫分析技术检测用药前后血清Ⅲ型前胶原 (PⅢP)、Ⅳ型前胶原 (PⅣP)、透明质酸 (HA)的含量变化 ,同时应用超声心动图记录左室结构及舒缩功能参数。结果　两组患者治疗 6月后血压均明显下降 (P <0 0 1) ,两组血压下降幅度比较无明显差异 (P >0 0 5 ) ,两组患者PⅢP、PⅣP、HA治疗 6月后均有下降 ,X A组下降明显 (与X组比较P <0 0 1) ,两组伴左室肥厚患者 (2 6例和 2 7例 )治疗 6月后室间隔厚度 (IVSD)、左室后壁厚度 (LPWD)、左室舒张末期内径 (LVIDD)、左室重量指数 (LVMI)较治疗前均有下降 ,但以X A组下降更明显 (与X组比较 ,P <0 0 5 ,P <0 0 1) ,同时 ,X A组左室舒张和收缩功能也得到明显改善 (P <0 0 5 ,P <0 0 1) ,两组均无明显不良反应发生。结论　缬沙坦与安体舒通联合治疗能更好地抑制肾素 -血管紧张素 -醛固酮系统 ,减轻心肌细胞外基质重塑 ,改善心室收缩和舒张功能 ,有利于提高EH患者的生活质量。     

Antimalarial activities of medicinal plants and herbal formulations used in Thai traditional medicine

Malaria is one of the world's leading killer infectious diseases with high incidence and morbidity. The problem of multidrug-resistant Plasmodium falciparum has been aggravating particularly in Southeast Asia. Therefore, development of new potential antimalarial drugs is urgently required. The present study aimed to investigate antimalarial activities of a total of 27 medicinal plants and 5 herbal formulations used in Thai traditional medicine against chloroquine-resistant (K1) and chloroquine-sensitive (3D7) P. falciparum clones. Antimalarial activity of the ethanolic extracts of all plants/herbal formulations against K1 and 3D7 P. falciparum clones was assessed using SYBR Green I-based assay. All plants were initially screened at the concentration of 50 μg/ml to select the candidate plants that inhibited malaria growth by ≥50 %. Each candidate plant was further assessed for the IC₅₀ value (concentration that inhibits malaria growth by 50 %) to select the potential plants. Selectivity index (SI) of each extract was determined from the IC₅₀ ratio obtained from human renal epithelial cell and K1 or 3D7 P. falciparum clone. The ethanolic extracts from 19 medicinal plants/herbal formulation exhibited promising activity against both K1 and 3D7 clones of P. falciparum with survival of less than 50 % at the concentration of 50 μg/ml. Among these, the extracts from the eight medicinal plants (Plumbago indica Linn., Garcinia mangostana Linn., Dracaena loureiri Gagnep., Dioscorea membranacea Pierre., Artemisia annua Linn., Piper chaba Hunt., Myristica fragrans Houtt., Kaempferia galanga Linn.) and two herbal formulations (Benjakul Formulation 1 and Pra-Sa-Prao-Yhai Formulation) showed potent antimalarial activity with median range IC₅₀ values of less than 10 μg/ml against K1 or 3D7 P. falciparum clone or both. All except G. mangostana Linn. and A. annua Linn. showed high selective antimalarial activity against both clones with SI?>?10. Further studies on antimalarial activities in an animal model including molecular mechanisms of action of the isolated active moieties are required.     

Moduratory Effect of Thai Traditional Medicine (Yahom Tultavai) on Hepatic Cytochrome P450 Enzymes and Pentobarbital-Induced Sleeping in Mice

Yahom Tultavai is a Thai traditional medicine that has been widely used for the treatment of nausea, vomiting, dizziness and weakness in aged-people, especially. Its formula contains several medicinal plants, and one of them is Kaempferia galanga L., which has ethyl-p-methoxycinnamate (EPMC) as its major compound. Recently, several herbs and traditional medicines have been reported to demonstrate herbal-drug interaction with conventional medicines. This study aims to investigate the effect of Yahom Tultavai extracts on hepatic cytochrome P450 enzymes and pentobarbital-induced sleeping in mice. Three extracts of Yahom Tultavai, using dichloromethane, methanol and distilled water as solvents were orally administered for 28 days prior to determine CYP1A1, CYP1A2, CYP2B, CYP2E1 and CYP3A4 activities. All three extracts significantly inhibited CYP1A1, CYP1A2 and CYP 2E1 activities, but only dichloromethane extract enhanced CYP2B activity. In addition, all three extracts had no effect on CYP3A4 activity. As an indicator for metabolic drug interaction, pentobarbital-induced sleeping time was decreased in connection with the induction of CYP2B activity between 7 and 28 days of dichloromethane extract and EPMC-treated animals when compared to control. In conclusion, Yahom Tultavai extracts affected hepatic microsomal CYP enzyme activities and reduced pentobarbital-induced sleeping time in mice. The results suggest that Yahom Tultavai may potentially cause herbal and conventional drug interaction, which can affect the clinical implication of drug action. Therefore, the co-administration of Yahom Tultavai with certain drugs should be carefully considered.     

Genetic polymorphisms of candidate markers and in vitro susceptibility of Plasmodium falciparum isolates from Thai-Myanmar border in relation to clinical response to artesunate–mefloquine combination

The genetic polymorphisms of the candidate markers of antimalarial drug resistance pfcrt, pfmdr1, pfatp6, and pfmrp1 were investigated in relationship with in vitro susceptibility of Plasmodium falciparum isolates and clinical response following artesunate (AS)–mefloquine (MQ) combination in 21 and 27 samples obtained from patients with recrudescence and adequate clinical response, respectively. MQ (21.0 vs. 49.9 nM) and AS (1.6 vs. 2.8 nM) IC₅₀ values (concentrations that inhibit parasite growth by 50%) were significantly higher in isolates collected from patients with recrudescence. Furthermore, a significantly higher MQ IC₅₀ was found in isolates from patients with recrudescence that carried pfmrp1 mutations at amino acid residues 191Y, 437A, and 876V. For AS sensitivity, a significant association was also detected in isolates from patients with recrudescence that carried gene mutations at amino acid residues 437A and 876V. MQ IC₅₀ of the isolates with recrudescence which carried ≥4 pfmdr1 gene copies was significantly higher than that carrying only one gene copy. In addition, a significantly higher proportion of isolates carrying one gene copy was detected in the group with adequate clinical response compared with recrudescence. Results from this limited sample size suggested the potential link between pfmdr1 gene copy number and pfmrp1 gene mutation, in vitro parasite susceptibility, and AS–MQ treatment response.     

Thai patients who fulfilled NCCN criteria for breast/ovarian cancer genetic assessment demonstrated high prevalence of germline mutations in cancer susceptibility genes: implication to Asian population testing

Breast Cancer Research and Treatment - Metastatic pattern (MP) is a prognostic factor in women with breast cancer. However, the prognostic significance of MP in male breast cancer patients remains...     

The reliability and validity of the therapeutic activity index

PURPOSE: To assess the psychometric properties of the Simplified Therapeutic Intervention Scoring System (TISS 28) scale. MATERIALS AND METHODS: A prospective observational design was used. Patients were recruited from a medical-surgical intensive care unit (ICU) and 4 rehabilitation wards of 2 university-affiliated hospitals in Hong Kong. RESULTS: Data necessary for the calculation of the TISS 28, the Therapeutic Intervention Scoring System (TISS 76), and severity of illness scoring system (Simplified Acute Physiology Score [SAPS II]) were recorded for each patient during the first 24 hours after his/her admission to an ICU. A significant positive correlation was found between the TISS 76 and the TISS 28 scores as well as the TISS 28 and the SAPS II scores. There was a significant difference between the TISS 28 scores among ICU patients and patients in rehabilitation wards. A significant correlation was found between the TISS 28 scores of the first and second set of TISS 28 scores. CONCLUSIONS: Although the findings supported the validity and reliability of the TISS 28, there were limitations of the TISS 28 in measuring nursing workload in ICUs. Hence, continued amendment and validation of the TISS 28 on larger samples in different ICUs would be required so as to provide clinical nurses with a valid and reliable assessment of nursing workload.     

Genotyping of polymorphic marker (MSP3α and MSP3β) genes of Plasmodium vivax field isolates from malaria endemic of Thailand

Two polymorphic marker genes, merozoite surface protein 3α (PvMSP3α) and merozoite surface protein 3β (PvMSP3β), from 100 Plasmodium vivax field isolates, were investigated using polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP). Genotyping of PvMSP3α and PvMSP3β revealed marked polymorphisms in length and sequence. Three major types of PvMSP3α (Type A, B and C) and two major types of PvMSP3β (Type A and B) were detected based on the length of PCR products. Fourteen alleles of both genes with difference frequencies were distinguished by restriction fragment length polymorphism, and these results strongly support that P. vivax isolates in Thailand are markedly diverse. PvMSP3α and PvMSP3β are reliable polymorphic markers for population genetic analysis of P. vivax, and PCR/RFLP provides a powerful method for genotyping and identification of mixed parasite infections without requirement of gene sequencing.     

Molecular analysis of pfatp6 and pfmdr1 polymorphisms and their association with in vitro sensitivity in Plasmodium falciparum isolates from the Thai-Myanmar border

The association between pfatp6, pfmdr1 polymorphisms (gene mutation and amplification) and in vitro susceptibility to mefloquine (MQ), artesunate (AS), quinine (QN), and chloroquine (CQ) was investigated in a total of sixty-three Plasmodium falciparum isolates collected from the Thai-Myanmar border. The mutations of pfatp6 at codons R37K, G639D, S769N, and I898I and of pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Pfatp6 and pfmdr1 gene copy numbers were analyzed by quantitative real time-polymerase chain reaction (qRT-PCR). In vitro susceptibility test was successful in 58 culture-adapted isolates. Median (range) IC(50) values for MQ, AS, QN, and CQ were 28.96 (3.4-100.5), 1.74 (0.8-5.57), 223.9 (14.99-845.47), and 69.93 (9.6-183.18) nM, respectively. There was a significant positive correlation (R(2) = 0.58) of parasite susceptibility to MQ, AS, and QN. Twelve isolates showed marked decline in susceptibility to AS [median (range) IC(50) = 3.78 (3.07-5.57) nM]. Almost all isolates carried wild-type pfatp6 and pfmdr1 alleles at the investigated codons, while only three isolates (5%) carried pfmdr1 mutation alleles at codon 86. Mutation at codon 86 was associated with a significant increase in the susceptibility of parasite isolates to MQ and QN. All of the sixty-three isolates carried only one pfatp6 copy number. Thirty-three out of the 58 isolates showed increase in pfmdr1 gene copies, which was associated with reduced in vitro susceptibility to MQ, AS, and QN. No association between mutation or amplification of pfatp6 gene and in vitro susceptibility of P. falciparum isolates was found.