Drug-loaded nanobubbles for ultrasound-mediated antitumor treatment.

Polylactic acid (PLA) bubbles that can act both as ultrasound contrast agents and drug carriers have the disadvantage of low encapsulation efficiency and do not allow effective extravasation into the tumor tissue. In this regard, PLA and lecithin are considered drug carriers. The present study used a modified ultrasonic double emulsion-solvent evaporation technology in order to prepare paclitaxel-loaded PLA-lecithin nanobubbles. X-ray diffraction analysis (XRD) was used to investigate the state of the drug in the bubbles, whereas the tumor weight and the inhibition rate of tumor bearing mice in the ultrasound-mediated function were further examined. The results indicated that the nanobubbles prepared with a mass ratio of PLA and lecithin at 50:250 were characterized as inner hollow. The size of these particles was approximately 615 nm, and the drug loading and encapsulation reached 8.34±0.67% and 91.42±5.48%, respectively. Paclitaxel was distributed in the shell of the bubbles in an amorphous state, and the in vitro drug release was characterized by sustained release, zero release and ultrasound mediated drug release. The injection of H22 hematoma-bearing mice with ultrasound-mediated drug-loaded PLA-lecithin nano-scaled bubbles could reduce the toxicity and increase the antitumor efficacy compared with paclitaxel.

Exposure Duration Is a Determinant of the Effect of Sinusoidal Electromagnetic Fields on Peak Bone Mass of Young Rats.

We proposed a three-step strategy to obtain the optimal therapeutic parameters, which is composed of large-scale screening at cellular level, verification in animal experiments, and confirmation by a clinical trial. The objective of the current study was to test the feasibility of our strategy. Newborn rat calvarial osteoblasts were treated by 50 Hz 1.8 mT sinusoidal electromagnetic fields (SEMFs) with 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 h/days, respectively. The osteogenic differentiation and maturation of the osteoblast were assayed and compared to obtain the optimal duration. One-month-old growing rats were then treated by the same SEMFs with 0.5, 1.5, and 2.5 h/days, respectively, and the peak bone mass was analyzed after 2 months. It was found that the optimal exposure duration to promote the osteogenic differentiation and maturation of osteoblasts was 1.5 h/days, judging by the increasing degrees of ALP activity, calcified nodules formed, the gene and protein expression levels of Runx-2, BMP-2, and Col-I, as well as the expression levels of signaling proteins of the BMP-2/Smad1/5/8 pathway. The highest increase of peak bone mass after 2 months was also obtained by 1.5 h/days, judging by the results of X-ray dual-energy absorptiometry, mechanical property analysis, micro-CT scanning, and serum bone turnover marker examinations. The above results indicated that exposure duration is a determinant for the therapeutic effect of EMFs, and the optimal therapeutic effects only can be obtained by the optimal exposure duration.

First Report of Leaf Blight on Saposhnikovia divaricata by Pseudomonas viridiflava in Gansu, China.

Saposhnikovia divaricata (Turcz) Schischk, a perennial plant in the Umbelliferae, is widely cultivated in north China. As a traditional Chinese medicine, it can be used to cure colds and rheumatism (1). During disease surveys on medicinal plants in August 2010, a bacterial leaf blight was discovered with a general incidence of 40 to 60% on S. divaricata farms in Longxi, Weiyuan County in Gansu China. In young plants, tiny yellow-white points were visible on the backs of the leaves. They then expanded to 2- to 3-mm oil-soaked lesions; leaves appeared crimped and deformed. Later the leaves shriveled; black-brown oil-soaked lesions appeared on the vein and the tissue around it; and black streaks appeared on the stems. Ten diseased leaf and stem tissues were cut into 4- to 5-mm squares, surface-sterilized in 1% sodium hypochlorite for 1 min, rinsed three times, and macerated for 5 min in sterilized distilled water. They were then streaked onto nutrient agar (NA) medium and incubated at 28°C for 3 days. Colonies on NA were round, smooth, translucent, and yellowish green. They were Gram negative and induced a hypersensitive response on tobacco (Nicotiana tabacum L.) leaves. The strain was positive for gelatin, catalase, oxidase, and utilization of glucose and saccharose. Pathogenicity tests were performed by spraying bacterial suspension containing 107 CFU/ml on six leaves of three healthy potted S. divaricata plants and injecting it into another six leaves on three plants. Plants inoculated with sterile distilled water alone served as controls. They were placed in a growth chamber at 25°C and bagged for 24 h to maintain >95% humidity. Thirty-six hours after inoculation, the inoculated leaves appeared water-soaked; 10 days later, the symptoms were apparent on leaves and the plant wilted. The negative control appeared normal. Finally, Koch's postulates were verified by re-isolating P. viridiflava from the leaves with typical blight. The genomic DNA of the isolate was extracted, and the partial 16S rDNA sequence was amplified with a universal bacterial primer set (27f and 1492r) (2). The sequence was deposited in GenBank as KM030291. BLAST search yielded 99% identity with P. viridiflava strains, including the strains KNOX209 (AY604847), RMX3.1b (AY574911), ME3.1b (AY574909), and UASWS0038 (AY919300). Based on the symptoms, colony morphology, biochemical tests, and 16S rDNA sequence identity, the pathogen was identified as P. viridiflava. To our knowledge, this is the first report of leaf blight of S. divaricata by P. viridiflava in Gansu province of China. In Jilin province, the same disease was reported in 2008 (3). The impact of P. viridiflava on S. divaricata production is not yet known. References: (1) Committee of China Pharmacopoeia. Pharmacop. People's Repub. 1:102, 2005. (2) C. Morenol et al. Microbiology 148:1233, 2002. (3) W. Xue. Dissertation. Jilin Agric. Univ. 1, 2008.

Clinical features, treatments and prognosis of the initial cases of pandemic influenza H1N1 2009 virus infection in Shanghai China.

BACKGROUND AND OBJECTIVE: As of 13 December 2009, more than 208 countries and overseas territories or communities have reported laboratory-confirmed cases of pandemic influenza H1N1 2009, which have resulted in at least 10 582 deaths. As of 7 December 2009, 4328 severe cases were reported in Mainland China, resulting in 326 deaths. This study's objective was to determine the clinical features, treatments and prognosis of the initial cases of Pandemic influenza H1N1 2009 virus infection in Shanghai, China, and how its clinical features related to patient gender. METHODS: A total of 224 confirmed 2009 influenza A/H1N1-infected patients treated and discharged by Shanghai Public Health Clinical center between 24 May and 20 July 2009 were included in the study. Patients' personal information, signs and symptoms, laboratory and imagery data, disease course, hospitalization period and seroconversion duration for viral nucleic acid after antiviral treatment were analyzed. RESULTS: Among the 224 patients, 118 were male and 106 were female, yielding a sex ratio of 1.1:1. Approximately 52% of the patients came from Australia, and 63.8% were between 18 and 40 years old. Clinical manifestations included fever, cough and congestion of the throat, and lab findings were characterized by elevated C-reaction protein (CRP) and neutrophils. Female patients had significantly lower serum Prealbumin (PA) levels than male patients (P < 0.05). The patients' serum CRF levels significantly decreased after treatment (P < 0.05), while the levels of CD3, CD4 and CD8 significantly increased after treatment (P < 0.01). Approximately 29.9% of the patients had abnormal signs on chest computer tomography scan, and 21.9% had obvious signs indicating pneumonia. However, blood cultures were negative in these patients. The average disease course was 3.9 +/- 1.4 days, the average hospitalization period was 5.0 +/- 1.7 days, and the seroconversion duration for viral nucleic acid after antiviral treatment was 3.8 +/- 1.3 days. CONCLUSION: Initial cases of pandemic influenza H1N1 2009 were characterized by fever, cough and throat congestion, with elevated CRP and neutrophils being the most significant lab findings. The pandemic influenza H1N1 2009 strain was able to affect multiple organs, including the hepatic synthesis of PA and immune functioning. The novel 2009 Influenza A/H1N1 virus was mild clinically, with a short disease course and good prognosis.

Stereotactic Gamma thalamotomy for the treatment of parkinsonism.

From September 1994 to June 1995, eight patients with intractable parkinsonism underwent gamma thalamotomy in our hospital. All of these patients were male, with an average age of 59.3 years. The duration of the disease from initial diagnosis was 2-10 years (mean 6.8 years). All had failed or had serious side effects with antiparkinsonian medicine. Seven cases had tremor-dominant symptoms, while the other had mainly rigidity. Six cases had bilateral symptoms. Computed tomography or magnetic resonance imaging (MRI) was undertaken prior to treatment in all cases to exclude focal brain lesions. Stereotactic MRI was taken with the Leksell frame in place and both T1- and T2-weighted images were obtained. The targets were located in the area of Vim/Voa/Vop based on the Schaltenbrand atlas. In seven cases, two plugged 4-mm-collimator shots were used. The maximum dose was 160 Gy in six cases and 180 Gy in one case. In another case, a single 4-mm-collimator shot was used, and a maximum dose of 160 Gy was delivered to the target center. The border of the internal capsule was outside the 20-30% isodose line. We intended the 50% isodose line to have an oval-shaped region with the use of two shots and should correspond to the shape of Vim. Follow-up data were available for six patients (mean: 4.5 months, range: 2-9 months). Tremor disappeared in three cases and improved in the other three. In one of these six cases, the tremor disappeared just 3 days after gamma thalamotomy. Rigidity improved in four of these six cases. In only one patient, treated with a maximum dose of 180 Gy, was there any contralateral limb weakness, which developed 3 months after treatment and has been recovering gradually. Follow-up MRI T2-weighted images in this case showed that the diameter of the lesion was larger than intended and there was a region of diffuse edema in the thalamus and upper brain stem. No other complications occurred in this series.

Capsaicin inhibits airway hyperresponsiveness but not lipoxygenase activity or eosinophilia after repeated aerosolized antigen in guinea pigs.

To evaluate the role of tachykinins in airway hyperresponsiveness following repeated aerosolized antigen challenge in guinea pigs, we treated 12 guinea pigs with capsaicin (105.6 mg cumulative dose given subcutaneously over 5 days) after sensitization to ovalbumin (OA) and before three repeated OA aerosol challenges per wk for 4 to 5 wk. Ten guinea pigs received identical OA sensitization and challenges without capsaicin treatment, and four of eight nonsensitized controls received capsaicin followed by saline challenges. Capsaicin treatment did not alter antibody responses to OA as assessed by passive cutaneous anaphylaxis, nor did it alter lipoxygenase products from OA-stimulated bronchial tissue in vitro. Capsaicin completely inhibited the increased pulmonary resistance (RL) to acetylcholine produced by repeated aerosolized OA, whereas it did not alter baseline RL or acetylcholine responses of controls. Capsaicin did not alter airway eosinophilia induced by repeated aerosolized OA. We conclude that neuropeptides play an important role in antigen-induced airway hyperresponsiveness without altering antibody levels, lipoxygenase mediator production, or airway eosinophilia.

Antimutagenic effect of garlic (Allium sativum L.) on 4NQO-induced mutagenesis in Escherichia coli WP2.

Aqueous extract prepared from garlic bulbs markedly suppressed the mutagenesis in both E. coli WP2 trp- and E. coli WP2 trp- uvrA- induced by 4-nitroquinoline 1-oxide (4NQO), but not that induced by UV. Cellular toxicity, inhibition of the expression of the Trp+ phenotype and delay of the first cell division after 4NQO treatment were not observed in the presence of the extract. Since the extract showed identical antimutagenic effects against 4NQO in both test strains but no effect on the mutagenesis of UV, it seems that the extract might act by inactivating the electrophilic group(s) of 4NQO or inhibiting its metabolic activation.