Correlation of the chemical structure of 4-nitroquinolines inactivating human cytomegalovirus and established in vivo carcinogenicity tests

Inactivation of the infectivity of human cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) has been observed following exposure to 4-nitroquinoline 1-oxide (NQO) or its metabolite, 4-hydroxyaminoquinoline 1-oxide (HAQO). The present study of the specificity of the chemical structure of 4-nitroquinolines demonstrated that both the 4-nitro and 1-oxide groups were required for inactivation of virus infectivity. Reduction of the 4-nitro group to a 4-hydroxyamino group enhanced activity, while further reduction to an amino group resulted in loss of activity against virus infectivity. The capacity to inactivate virus was also lost by substitution of the pyridine ring for the quinoline nucleus of NQO. The relationship between the chemical structure and the ability to inactivate viruses studied here correlates well with earlier in vivo carcinogenicity studies of the same group of chemicals.     

A rare case of primary Ewings sarcoma of the nasal bone

Primary Ewing’s sarcoma of the nasal bone has not been previously described. This case presented as a mass in the left ala of the nose in a five year old female child. The clinical, radiological, microscopic features are described and a review of literature is presented. The case was treated with neoadjuvant chemotherapy and local electron beam radiation therapy. The child was free of disease when she reported for follow up in July 1997. Although wide excision is part of the treatment approach in Ewing’s sarcoma, in sites where surgery is not suitable local radiotherapy and chemotherapy adequately controls primary disease.     

Transabdominal near infrared oximetry of hypoxic stress in fetal sheep brain in utero

The feasibility of transabdominal near-infrared (NIR) spectroscopy for detecting and quantifying fetal hypoxia in utero is demonstrated in a pregnant ewe model. A frequency domain NIR spectroscopy probe, consisting of two detectors and six sources operating at three wavelengths (675, 786, and 830 nm), was placed on the maternal abdomen directly above the fetal head. Fetal hypoxia was indirectly induced through occlusion of uterine blood flow for approximately 3 min. NIR photon diffusion measurements were made during a baseline period, during hypoxia of the fetus, and during recovery. Fetal blood samples were drawn from the fetal brachial artery and jugular veins at several time points during the cycle. Seven hypoxic cycles were induced in a total of five pregnant ewes. The NIR measurements were analyzed by using a two-layer diffusion model to deconvolve the fetal blood saturation from that of the pregnant ewe. Fetal hypoxia was detected. Good agreement was found between fetal blood saturation determined by the transabdominal NIR method and arterial and venous fetal blood saturation quantified from fetal blood samples by using a hemoximeter.     

Molecular diagnosis of ureaplasma urealyticum septic arthritis in a patient with hypogammaglobulinemia

Objective. We report a hypogammaglobulinemic patient with a destructive oligoarticular arthritis, whose synovial fluid cultures were repeatedly sterile. Methods and Results. We identified a Ureaplasma urealyticum infection in his affected joints, using a polymerase chain reaction (PCR) assay. Conclusion. The PCR technique promises to be extremely valuable in the rapid and specific diagnosis of infectious arthritis.     

BAFF blockade for systemic lupus erythematosus: will the promise be fulfilled?

Summary: Systemic lupus erythematosus (SLE) is a complex immune disorder in which loss of tolerance to nucleic acid antigens and other cross-reactive antigens is associated with the development of pathogenic autoantibodies that damage target organs including the skin, joints, brain, and kidney. B cells are essential to lupus pathogenesis, not only because they produce pathogenic autoantibodies but also because they have multiple effector functions in the immune system. There has been much recent interest therefore in targeting of B cells for the treatment of SLE and other autoimmune diseases. BAFF (B-cell activation factor belonging to the tumor necrosis factor family) is a crucial homeostatic cytokine for B cells that is upregulated during inflammation and links adaptive with innate immunity. Excessive levels of BAFF may alter selection of autoreactive B cells and contribute to perpetuation of SLE by a variety of mechanisms. BAFF antagonists have been effective in the prevention and treatment of SLE in several different murine models. Three classes of BAFF antagonists have been developed for clinical use, and initial clinical trials have begun. However, immune modulation in SLE is complicated by differences in the immune defects between patients and at different disease stages. Further work will be needed both in animal models and humans to determine the most appropriate clinical applications for BAFF blockade.     

Interferon‐α treatment of female (NZW × BXSB)F1 mice mimics some but not all features associated with the Yaa mutation

Objective

Male (NZW × BXSB)F₁ mice develop antiphospholipid syndrome (APS) and proliferative glomerulonephritis that is markedly accelerated by the Yaa locus encoding an extra copy of Tlr7. Female (NZW × BXSB)F₁ mice with only 1 active copy of Tlr7 develop late‐onset glomerulonephritis but not APS. Because a major function of Toll‐like receptor 7 is to induce type I interferons (IFNs), our goal was to determine whether IFNα can induce or accelerate the manifestations of systemic lupus erythematosus (SLE) in female (NZW × BXSB)F₁ mice.

Methods

Eight‐week‐old female (NZW × BXSB)F₁ mice were injected with a single dose of adenovirus expressing IFNα. Mice were monitored for the development of thrombocytopenia and proteinuria. Sera were tested for anticardiolipin and anti‐Sm/RNP antibodies. Mice were killed at 17 or 22 weeks of age, and their kidneys and hearts were examined histologically and by immunohistochemistry. Spleen cells were phenotyped, and enzyme‐linked immunospot assays for autoantibody‐producing B cells were performed.

Results

IFNα markedly accelerated nephritis and death in female (NZW × BXSB)F₁ mice. A significant increase in spleen cell numbers associated with a striking increase in the number of activated B and T cells was observed. Marginal‐zone B cells were retained. IFNα‐induced increased titers of autoantibodies were observed, but thrombocytopenia was not observed. Cardiac damage was milder than that in male mice.

Conclusion

IFNα accelerates the development of renal inflammatory disease in female (NZW × BXSB)F₁ mice but induces only mild APS and does not induce thrombocytopenia. The effect of IFNα on SLE disease manifestations is strain dependent. These findings are relevant to our understanding of the physiologic significance of the IFN signature.

     

Unusual presentations of aorto-enteric fistula

BACKGROUND: Aorto-enteric fistula is rare but can result in exsanguination without timely surgery or endovascular stent placement. METHODS: Four cases of aorto-enteric fistula were reviewed in which the presentation was unusual and diagnosis difficult. OBSERVATIONS: The first patient had an aorto-sigmoid fistula in the setting of an aorto-bi-femoral graft. Two patients had a primary aorto-enteric fistula, one to the stomach from a suprarenal aortic aneurysm, and the other, to the duodenum in the setting of retroperitoneal spread of renal cancer. The aortoduodenal fistula recurred in the 4th patient within 3 months of surgical repair; this patient is the only one who survived long term. CONCLUSIONS: When presentation is atypical, the diagnosis of aorto-enteric fistula can be extremely difficult. Because investigative studies are not consistently useful in making a definitive pre-operative diagnosis, a strong index of clinical suspicion and a willingness to consider surgical exploration are essential for timely and successful management.     

Triangulating stapling technique: An alternative approach to colorectal anastomosis

The triangulating stapling technique was employed to perform colorectal anastomosis in 259 patients. In 220 patients, the anastomosis was performed between the colon and nonperitonealized rectum. This anastomotic technique is safe and reliable and is an effective alternative to a circular stapling device, with minimal morbidity. The incidence of leak rate is comparable to anastomoses created by a circular stapling device. The main advantage seems to be the very low incidence of anastomotic stenosis.     

Curcumin- and natural extract-loaded nanofibres for potential treatment of lung and breast cancer: in vitro efficacy evaluation

Drug-eluting medical implants are more common, particularly for fighting against cancers. FDA and other drug regulatory bodies have approved many nanoformulated devices eluting active pharmaceutical ingredients and thus there is growing demand for further value- added devices. Nanofibre membranes are known for its versatility of drug incorporation and sustained drug release. We intend to fabricate natural ingredient or extract, and their combination loaded polycaprolactone (PCL) nanofibre for usage as drug-eluting stents or implants for anticancer activity against lung and breast cancers. The fabricated nanofibre membranes were characterised by scanning electron microscope for morphology, FT-IR for chemical nature and tensile testing for mechanical strengths. Release of curcumin was studied with time to find the applicability of the device as drug-eluting implant. The activity of the nanofibre membranes was tested against human breast cancer (MCF7) and lung cancer (A459) cell lines in vitro. In both the cell lines tested, 1% aloe vera and 5% curcumin-loaded PCL nanofibre exhibited 15% more cytotoxicity in comparison with the commercial drug 1% cis-Platin-loaded PCL nanofibre after 24?h incubation.