Appropriate Needle Lengths Determined Using Ultrasonic Echograms for Intramuscular Injections in Japanese Infants

Adjuvanted vaccines are recommended for administration through an intramuscular route. The Centers for Disease Control and Prevention (CDC) has recommended the anterolateral thigh using a 22 - 25-G 25-mm (1 inch) needle for infants, injected at a 90° into the skin surface, and using a 16 mm (5/8 inch) for newborns. Appropriate needle lengths may differ depending on racial backgrounds. In the present study, the thickness of the epidermis and lengths from the skin surface to the muscle fascia and bone were measured using ultrasonic echograms in order to determine suitable needle lengths for Japanese infants aged 2, 3, 4, 5, 6, and 12 - 15 months old. The thickness of the epidermis was 1.44 - 1.54 mm (95% CI), and the lengths from the skin surface to the muscle fascia and bone were 11.52 - 12.28 mm (95% CI), and 25.66 - 26.93 mm (95% CI), respectively, at the anterolateral thigh. At the center of the deltoid muscle, skin thickness was similar to that at the thigh, furthermore the lengths from the skin surface to the muscle fascia and bone were 8.49 - 9.10 mm (95% CI), and 17.38 - 18.31 mm (95% CI), respectively. The lengths from the skin surface to the muscle fascia and bone were 1 - 2 mm shorter in 2-month-old infants than those in older generations. Therefore, the appropriate needle length for intramuscular injections in Japanese infants was 16 mm (5/8 inch) at any age and sites, and with 25 mm (1 inch) needles at a 90° angle being associated with the risk of over-penetration.

日本汉方药中对免疫和神经系统的活性成分和可能作用机制(英文)

Abatract:Many of the diseases are multifactorial and still difficult to treat by only modern medicines,however Kampo medicines,which contain multiple ingredients due to component herbs,seem to be suitable for recovery of such complicated symptoms because these ingredients may attack multiple target sites to improve the symptoms caused by disturbance of whole body system.In Japan,148 standardized Kampo pharmaceutical preparations have been developed,and covered by national health insurance system,and more than 80% practicing physicians have experience of using the Kampo medicines for the treatment depending on patient′s clinical situation,either separately or to complement modern western medicines.In present paper,I′d like to introduce few examples of our studies on elucidations of pharmacological actions and active ingredients of Kampo medicines as multi-ingredients drugs.Although Kampo medicines have been taken orally as the decoction,their hot water extracts contain not only low molecular ingredients but also high molecular ingredients like polysaccharides.Our recent studies suggest that Hochuekkito(HET:Bu-Zhong-Yi-Qi-Tang)prevents respiratory infection through potentiation of mucosal immune system in upper respiratory tract,and certain pectic polysaccharides were identified to involve in potentiation of the immune response.It was also clarified that synergic action of two stereoisomers are required for the oral adjuvant activity of Shoseiryuto(SST:Xiao-Qing-Long-Tang).Like examples of the studies of Kososan(KS:Xiao-Su-San)and SST,proteomic analysis of disease model animals using agarose 2-DE is also useful another approach to find target protein candidates.These accumulated comprehensive results may contribute for more evidence-based clinical application.

Clinical Trial of Measles and Rubella Combined Vaccine Produced by POLYVAC in Vietnam

A clinical trial of measles and rubella combined vaccine (MR: MRVAC) produced by POLYVAC was conducted in Vietnam in 2016. A total of 756 subjects were enrolled, and 504 were allocated to MRVAC and 252 to control MR vaccine groups. Paired sera were obtained in 733, and the number of subjects was 403 aged 1 - 2 years, 164 aged 2 - 18 years, and 166 aged 18 - 45 years. Antibodies against measles and rubella viruses were evaluated by EIA. Most subjects had been immunized with a single dose of Expanded Programme on Immunization (EPI) measles vaccine at 9 months of age. Only 41 of 403 subjects aged 1 - 2 years were negative for measles antibody before vaccination, and all became seroconverted. A serological response of more than a 2-fold increase against measles was noted in 214 (47%, 95% CI;42.4% - 51.6%) of 458 initially seropositive individuals immunized with MRVAC and 65 (28%, 95% CI;22.3% - 33.8%) of 234 in the control group, and geometric mean titer (GMT) after vaccination was 25.49-5.60 in MRVAC and 25.03-5.24 in control group. Seroconversion against rubella virus after immunization with MRVAC was noted in 267 (98.5%, 95% CI;97.1% - 100%) of 271 initially seronegative subjects, similar to that after immunization with control group. GMT after immunization with MRVAC was 24.88-5.11 significantly lower than that after immunization with control vaccine (25.59-5.80). Most subject ≥ 2 years of age had rubella antibody because of MR vaccination campaign and no significant serological response was observed in initially seronegatives. MRVAC was highly immunogenic and safe vaccine and the domestic production of MR vaccine would contribute to realizing the goal of eliminating measles and rubella.

Change of Subcutaneous Tissue Mass at the Deltoid and Thigh Areas in Japanese Infants Followed from 2 to 15 Months

We previously investigated the thickness of the epidermis and lengths from the skin surface to the muscle fascia and bone based on measurements taken from the ultrasonic echograms of Japanese infants aged 2, 3, 4, 5, 6, and 12 - 15 months. The appropriate needle length for intramuscular injection was 16 mm (5/8 inch) in Japanese infants at any age and site. In the present study, we examined these lengths in 21 infants with physical growth from 2 to 15 months. Average height increased from 58.5 to 73.6 cm and average body weight from 5835 to 9226 g until 15 months. The circumference of the thigh increased from 22.3 cm at 2 months to a maximum of 25.9 cm at 6 months, while that of the deltoid area was 15.2 cm at 2 months and 15.9 cm at 6 months. Subcutaneous mass (length from the skin surface to the muscle fascia) at the thigh increased between 3 and 4 months and decreased at 12 - 15 months and showed good relationship to the circumference of the thigh. Subcutaneous mass at the center of the deltoid area showed the same size until 6 months. Muscle mass (lengths from the muscle fascia to the bone) at thigh and deltoid areas remained the same until 6 months. Ultrasonic echogram is an effective tool for evaluating subcutaneous and muscle mass in young infants.

Sero-Epidemiological Study of Respiratory Syncytial Virus

Background: Respiratory syncytial virus (RSV) is one of the major viruses that cause respiratory infections in all generations, not only in neonates and infants. There is a limited number of reports on serological epidemiology of RSV subgroups A and B. Neutralizing test (NT) antibody reflects protective immunity but bothersome. Sero-epidemiological study should be performed using practical NT method. Methods: Two wild-type viruses subgroups A and B, isolated in 2013, and the Long strain was used as the challenge viruses. NT antibody with 100% inhibition of cytopathic effect (CPE) was examined. A total of 91 serum samples obtained from 0 to 12 years subjects without RSV infection who visited our hospital with some health problems and 121 sera obtained from healthy subjects in different age groups were used. Serological epidemiology of subgroups A and B was investigated in this study using new NT methods. Results: 1) A simple and practical NT method was developed. 2) The NT antibody titer was lowest in <1 year of age (5 × 21.70 ± 2.03 against subgroup A and 5 × 20.85 ± 1.31 against subgroup B) and increased in 3 years of age or older, and high antibody titers were maintained during school age. 3) A slight difference was observed in the NT antibody titers against subgroups A and Bin young children <3 years, but not after 3 years of age, reflecting the repeated infections. 4) Specific IgG antibody against RSV was measured. The IgG EIA values decreased with age. No association was observed between IgG EIA and NT titers. Conclusions: A simple NT assay method was developed in the present study. By the age of 3 years, high NT antibody titers were observed and maintained until 12 years. The IgG (EIA) values decreased with age. No association was observed between IgG (EIA) and NT titers.

Antitumor Effects and Acute Oral Toxicity Studies of a Plant Extract Mixture Containing <i>Rhus verniciflua</i>and Some Other Herbs

A novel antitumor agent was developed from six kinds of herbs containing Rhus verniciflua (Rv-PEM01). The components were traditionally established for each formula for traditional medicine. The formula was designed to affect antitumor effect as well as maintain host immune functions. First, we investigated the antiproliferative activities of Rv-PEM01 on human and canine tumor cell lines in vitro, and on antitumor effects using BALB/cAJcl-nu/nu mice in vivo. Acute oral toxicity of Rv-PEM01 was also investigated in vivo in ddY mice. Rv-PEM01 exhibited antiproliferative activities against PC-3 (IC50: 0.328 ± 0.081 mg/ml), A549 (IC50: 0.520 ± 0.070 mg/ml), D-17 (IC50: 0.124 ± 0.037 mg/ml) and MRC-5 (IC50: 0.505 ± 0.058 mg/ml) cells. Luteolin 7-β-D-glucopyranoside and apigenin 7-β-D-glucopyranoside were identified as the main active compounds in Rv-PEM01 by HPLC analysis. The single dose toxicity study of Rv-PEM01 did not result in any deaths or abnor-malities in daily behavior, body weight gain, or anatomical observations at necropsy. Thus, so we could not calculate the 50% lethal dose (LD50) in mice, but it would be higher than 5.0 g/kg. Treat- ment with Rv-PEM01 at a dose of 2.5 g/kg tended to show antitumor activities on mice bearing Colon26 tumors compared with the control group. It was concluded that the formula was a safe antitumor agent with no side effects on mouse physiological function as judged by survival and organ weight.

Clinical Effects of a Plant Extract Mixture Containing Rhus verniciflua and Other Herbs in Tumor Bearing Dogs

Dog owners are increasingly seeking treatment when their pets develop cancers. As in human cancer patients, dogs with cancer are commonly treated with complementary and alternative therapies, including herbal medicines and nutritional supplements. A novel antitumor agent was developed from six different herbs including Rhus verniciflua (Rv-PEM01). The components were established from traditional herbal medicine and designed to affect antitumor activity and maintain host immune function. Previous studies identified anti-proliferative activity in human, murine and canine cancer cell lines. In this clinical study the safety and tolerability of Rv-PEM01 were evaluated in pet dogs with spontaneously occurring cancers. Twelve dogs were treated orally daily for 30 days in escalating dose (4 - 10 mg/kg orally once daily) cohorts. Rv-PEM01 was well tolerated;only transient mild elevations in BUN were observed in 2 dogs. Although tumor response was not a primary endpoint for this study, stable disease was maintained for 30 days in 5 (42%) of the dogs. In conclusion, Rv-PEM01 was found to be safe and well tolerated in the dosage range tested. Future studies should evaluate higher dosages of Rv-PEM01 in dogs with cancer, and specifically address other potential benefits of Rv-PEM01 in canine cancer patients, including correlative assessments of immune function, quality of life and owner satisfaction.

结核感染若干年后特异性γ-干扰素应答减弱

假设:随着时间的流逝,结核感染者记忆性T细胞对特异性抗原的应答减弱。背景:很多证据表明特异性全血γ-干扰素(IFN-γ)检测试验Quanti-FERON-TB Gold (QFT-G)能够检测出近期结核感染者,并具有较高的灵敏度和特异性。目的:我们应用此项技术检测日本一个社区的成人群体以确定其流行病学应用价值。方法:1559例参加定期体检的健康志愿者入选本研究。结果:40～49岁人群QFT-G的阳性率为3.1%,50～59岁人群的阳性率为5.9%,60～69岁人群的阳性率为9.8%。作者根据一系列研究估计40～49岁、50～59岁、60～69岁的预期结核感染率分别为11.1%、29.6%、53.1%。预期阳性率与实际阳性率之间存在的巨大差异提示结核感染后随着时间的延长IFN-γ应答减弱。那些经胸部X线证实存在陈旧性结核病灶者阳性率大大低于100%。结论:特异性IFN-γ应答可能在结核感染后随着时间的推移大大地减弱。需要在感染者中长期地纵向研究细胞介导的免疫动力学。

New cyslabdans B and C, potentiators of imipenem activity against methicillin-resistant Staphylococcus aureus produced by Streptomyces sp. K04-0144

From a further purification study,two new congeners designated cyslabdans B(1)and C(2)were isolated along with previously reported cyslabdan(cyslabdan A(3)in this study)from the culture broth of Streptomyces sp.K04-0144.The structure was elucidated by various spectroscopy including NMR,revealing that 1 and 2 was 18-hydroxy and 10-methoxy cyslabdan,respectively.Compounds 1 and 2 were found to potentiate imipenem activity against methicillinresistant Staphylococcus aureus by 123 fold and 533 fold,respectively.Comparison with the activity of compound 3 indicated that the introduction of a hydrophilic group at the dimethyl moiety of the decalin ring was unfavorable for its activity.

Beauvericin counteracted multi-drug resistant Candida albicans by blocking ABC transporters

Multi-drug resistance of pathogenic microorganisms is becoming a serious threat,particularly to immunocompromised populations.The high mortality of systematic fungal infections necessitates novel antifungal drugs and therapies.Unfortunately,with traditional drug discovery approaches,only echinocandins was approved by FDA as a new class of antifungals in the past two decades.Drug efflux is one of the major contributors to multi-drug resistance,the modulator of drug efflux pumps is considered as one of the keys to conquer multi-drug resistance.In this study,we combined structure-based virtual screening and whole-cell based mechanism study,identified a natural product,beauvericin(BEA)as a drug efflux pump modulator,which can reverse the multi-drug resistant phenotype of Candida albicans by specifically blocking the ATP-binding cassette(ABC)transporters;meantime,BEA alone has fungicidal activity in vitro by elevating intracellular calcium and reactive oxygen species(ROS).It was further demonstrated by histopathological study that BEA synergizes with a sub-therapeutic dose of ketoconazole(KTC)and could cure the murine model of disseminated candidiasis.Toxicity evaluation of BEA,including acute toxicity test,Ames test,and hERG(human ether-a-go-go-related gene)test promised that BEA can be harnessed for treatment of candidiasis,especially the candidiasis caused by ABC overexpressed multi-drug resistant C.albicans.