Composition of PLGA and PEI/DNA nanoparticles improves ultrasound-mediated gene delivery in solid tumors in vivo

The goal of this study was to enhance gene delivery and tumor cell transfection in vivo by using a combination of ultrasonication with complex nanoparticles consisting of two types of nanoparticles: PEI/DNA β-gal plasmid with highly positive zeta-potential and air-filled poly (lactic-co-glycolic acid) (PLGA) particles (with negative zeta-potential) manufactured in our laboratory. The PLGA/PEI/DNA nanoparticles were a colloid with positive zeta-potential and injected i.v. in nude mice with DU145 human prostate tumors. We found that the combination of PLGA/PEI/DNA nanoparticles with ultrasonication substantially enhanced tumor cell transfection in vivo. The overexpression of β-gal gene was evaluated histochemically and by Western blot analysis. At least an 8-fold increase of the cell transfection efficacy was obtained in irradiated tumors compared to non-irradiated controls, while little to no cell death was produced by ultrasonication.     

阿德福韦双酯治疗拉米夫定耐药的慢性乙肝患者时出现的耐药问题

背景:阿德福韦双酯(ADV) 是一种有效治疗野生型和耐拉米夫定乙肝病毒(HBV)的核苷酸类药物。在使用核苷酸类药物治疗慢性乙肝时,当治疗时间为 48、96、144周时,耐ADV变异体出现的累积发生率分别为0、 0．8-3％和0-5．9％。目的:研究67例对拉米夫定耐药且接受ADV治疗的慢性乙肝患者耐ADV病毒变异体的表型和基因型特点。方法:HBV DNA含量采用实时定量PCR技术。ADV变异体检测采用基质辅助激光解吸电离／飞行时间质谱为基础的基因分型     

Alcohol consumption during pregnancy and the risk of early stillbirth among singletons

The purpose of this study is to investigate the association between maternal alcohol intake in pregnancy and the occurrence of early stillbirth using a retrospective cohort analysis of singleton births in Missouri that occurred in the period 1989 through 1997 (N=655,979). We used Cox proportional hazards regression to generate adjusted risk estimates for total, early, and late stillbirth associated with maternal alcohol intake and used the Robust Sandwich Estimator to adjust for intracluster correlations among sibships. Overall, a total of 3,508 counts of stillbirth were identified, yielding a stillbirth rate of 5.3 per 1,000. Among mothers who consumed alcohol during pregnancy, the stillbirth rate was 8.3 per 1,000. Mothers who consumed alcohol while pregnant were 40% more likely to experience stillbirth as compared with nondrinking mothers (adjusted hazards ratio=1.4, 95% confidence interval: 1.2-1.7). A dose-response relationship was evident; mothers who consumed five or more drinks per week during pregnancy experienced a 70% elevated risk of stillbirth compared with nondrinking mothers (adjusted hazards ratio=1.7; 95% confidence interval: 1.0-3.0). The risk of early stillbirth was 80% higher among drinking mothers compared with abstainers (adjusted hazards ratio=1.8; 95% confidence interval: 1.3-2.3). The elevated risks for both early and late stillbirth did not reach statistical significance when broken down by level of alcohol intake. In conclusion, maternal drinking during pregnancy is associated with an increased risk of early stillbirth. These findings underscore the need to reinforce current counseling strategies toward pregnant women and women who intend to conceive on the detrimental effects of alcohol use in pregnancy.     

The reversible antifertility effect of Piper betle Linn. on Swiss albino male mice

To study the antifertility effect of an extract (alcoholic) of the leaf-stalk of Piper betle Linn., one set of experiments with two different doses in Swiss male albino mice were evaluated. Initially, 500 mg of the leaf-stalk extractive for 30 days and then 1000 mg for next 30 days/animal/day/kg body weight were administered orally. The extract reduced fertility to 0% within 60 days. Suppression of cauda epididymal sperm count and motility (p <0.05) was observed. Biochemical parameters did not show any marked alterations in testosterone content in serum nor 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity in testes although fructose content in seminal vesicles was reduced as are the weights of reproductive organs. The cholesterol content in testes increased, although not appreciably. After cessation of drug (plant extract) treatment, the altered parameters recovered. Results suggest that the contraceptive effect of the extract of leaf-stalk of Piper betle Linn. is mainly on the maturation process of spermatozoa in epididymides without influencing hystemic hormonal profiles. Withdrawal of the extract restored all altered parameters including organ weights and fertility after 60 days.     

Plasma cell leukemia masquerading as ALL-L3--a case report

Plasma cell leukemia (PCL) is a rare type of plasma cell dyscrasia. It is diagnosed when circulating plasma cells (PC) are more than 20%. We present a case of PCL in a 62-year-old female. Peripheral smear revealed more than 80% atypical vacuolated plasma cells (Mott cells) almost mimicking Burkitt cells of Acute Lymphoid Leukemia-L3 (ALL-L3). Bone marrow aspirate revealed few mature myeloma cells for which a diagnosis of PCL was thought of. Serum electrophoresis showed a positive M-band and X-ray revealed lytic lesions over femur & pelvic bones. A final diagnosis of PCL was given.     

Motor but not sensory representation in motor cortex depends on postsynaptic activity during development and in maturity

The movement representation in the primary motor cortex (M1) of the cat develops between postnatal weeks 7-12. The somatosensory representation in motor cortex is present by the age that the motor map begins to develop. In this study we examined the role of neural activity in development and maintenance of the M1 movement and somatosensory representations. We blocked activity of M1 neurons unilaterally for one month by intracortical infusion of the GABA agonist muscimol during the motor map development period in kittens and in mature cats. After the drug effects were no longer present, we used microstimulation and multiunit recording in the forelimb areas of M1 to determine the motor and somatosensory representations in the infused and noninfused sides. In both kittens and adults, there was a severe reduction or elimination of sites where microstimulation evoked a motor response in the inactivated compared with the control side. In contrast, there was no difference in the percentage, topography or receptive field modality of sites receiving somatosensory inputs on the inactivated and control sides. Moreover, the pattern of somatosensory input to M1 was similar before and after inactivation. This suggests that somatosensory input to M1 is stable after the connections initially develop. Since activity blockade had the same effects on the motor representation of kittens and adult cats, M1 neuronal activity, while possibly important in map development, is equally necessary for map maintenance.     

Treatment of Allergic Bronchopulmonary Aspergillosis with Fluconazole and Itraconazole

Treatment of allergic bronchopulmonary aspergillosis (ABPA) has remained both problematic as well as controversial. Although the sheet anchor in treatment of ABPA still remains steroids, various workers have tried oral antifungals (fluconazole and itraconazole) with encouraging results. This study evaluates the effect of fluconazole or itraconazole in the treatment of ABPA patients and compares them with the patients who had received palliative therapy other than antifungals. Case records of 44 proven cases of ABPA treated at our referral service hospital during February 1998 to April 2001 were analyzed. In addition to oral and inhaled bronchodilators, 16 patients received fluconazole 150 mg OD and 13 patients itraconazole 200 mg OD for six months. Response to therapy was assessed clinically, radiologically and by spirometry every 3 months. Patients who did not receive antifungals had chronic course characterized by airway obstruction, recurrent pulmonary consolidation and obstructive defect on pulmonary function test (PFT). Patients treated with itraconazole had better control of asthma symptoms, less requirement of reliever inhalers, steroids and lesser exacerbations of asthma during follow-up even after stopping antifungal. Fluconazole group had better control of symptoms but improvement in other parameters was not statistically significant. From this study it was evident that itraconazole improved the symptoms of airway obstruction, pulmonary functions, pulmonary opacities and decreased exacerbations during follow up.Key Words: Allergic bronchopulmonary aspergillosis, Fluconazole, Itraconazole     

Mantle cell lymphoma in lymph nodes with metastatic small cell carcinoma of lung: a diagnostic and treatment dilemma

We report a rare case of small cell carcinoma (SCC) of lung, metastatic to ipsilateral hilar and peribronchial lymph nodes with synchronous mantle cell lymphoma (MCL), in a 58-year-old female. She was treated with Cisplatin, Etoposide, and Rituximab, and remained in complete remission for approximately two and a half years following the initial diagnosis. To the best of our knowledge, synchronous SCC and MCL or SCC metastatic to lymph nodes involved by MCL has not been previously reported. In this case, the features of MCL were very inconspicuous in the lymph nodes with extensive metastases of SCC. The presence of MCL was confirmed by immunohistochemistry and fluorescence in situ hybridization (FISH). The co-existence of lymphoma and metastatic carcinoma in the same lymph node, as seen in this case, highlights the significance of analyzing subtle lymphoid architectural changes, and applying ancillary studies such as immunohistochemistry and molecular analysis in suspicious cases. The management of synchronous SCC and MCL requires consideration of their respective biologic behavior, and cumulative toxicity of treatment regimens of both tumors. In such cases an optimum treatment strategy should be adopted to cover both malignancies with minimal toxic effect.     

Platelet-activating factor activates mitogen-activated protein kinases,inhibits proliferation,induces differentiation and suppresses the malignant phenotype of human colon carcinoma cells

Recent studies suggest that the action of platelet-activating factor (PAF), a potent phospholipid modulator of allergic and inflammatory reactions, is diverse and functions as a modulator of a variety of physiological and pathological events in many cell types and tissues. Its role (if any) in modulating the proliferation, transformation and/or differentiation of epithelial colonic cells, however, is not known. In this study, we showed that PAF is biologically active in epithelial-derived human colon carcinoma cells with different phenotypic properties. These cells expressed the PAF receptor. PAF activated three prominent mitogen-activated protein kinase modules (ERK, p38MAPK and Jun N-terminal kinases) in these cells, inhibited proliferation and induced differentiation (measured by the induction of Waf1/p21 and the induction of the differentiation-related marker CEA). The net effect of PAF treatment was the suppression of malignant cell behavior (measured by anchorage-independent growth and cellular invasion). It is concluded that PAF is a modulator of proliferation and differentiation in human epithelial-derived colon carcinoma cells.