Potent inhibition of respiratory syncytial virus by combination treatment with 2-5A antisense and ribavirin

Respiratory syncytial virus (RSV) is a major cause of lower respiratory diseases in infants, young children, and the elderly. Ribavirin, the only currently approved drug for the treatment of RSV infections in the U.S., requires high doses to be effective. Therefore, it has only a limited clinical efficacy in the treatment of RSV infections. It has been shown that a cellular ribonuclease, RNase L, can be recruited by 2'-5' linked tetra-adenylates (2-5A) attached to an antisense sequence complementary to the RSV genome to specifically cleave RSV genomic RNA. Here we confirm the antiviral activity of the lead 2-5A antisense compound, RBI034, by using several different viral assays. We demonstrate that RBI034 is more efficient than antisense lacking 2-5A or small interfering dsRNA (siRNA) in inhibiting RSV replication. Although the best antiviral activity of RBI034 was observed with co-treatment of RSV infection, it remained effective even when administered 24 h after the initiation of infection. Interestingly, the activity of RBI034 can be further enhanced by a combination treatment with ribavirin. At suboptimal concentrations, neither ribavirin nor RBI034 was effective in suppressing RSV replication. However, a combination of these two drugs at the same suboptimal concentrations showed a potent inhibitory activity. The potent reduction of RSV replication by combination treatment was also confirmed in primary human airway epithelial cells. Therefore, a combination therapy of the 2-5A antisense compound RBI034 and ribavirin might be a more effective therapeutic approach for treating RSV infections than ribavirin alone.     

An unusual case of primary nasal tuberculosis with epistaxis and epilepsy

Primary nasal tuberculosis is rare. We report a case that was all the more extraordinary because of the age and sex of the patient (an 11-year-old boy), the unusual associated symptoms (epistaxis and grand and seizures), and the presence of intracranial extension. Clinical and radiologic findings on our initial evaluation suggested that the patient had a large sinonasal malignancy. The patient manifested no evidence of pulmonary tuberculosis. The diagnosis of primary nasal tuberculosis was established only after we obtained the results of histopathology of the excised mass and a subsequent tuberculin skin test; the diagnosis was confirmed by the patient's rapid response to antituberculosis drug therapy. We also review the relevant literature on this rare condition.     

Effect of textile waste water on the spermatogenesis of male albino rats

Textile waste water released from dyeing and printing industries situated in Sanganer, Jaipur (India), brought about inhibition of spermatogenesis in male rats. Water analysis showed the presence of heavy metals at more than permissible limits. Oral administration of waste water to the rats at the dose level of 26.6 ml kg(-1) body wt. significantly reduced the weights of testes, epididymides and seminal vesicle. Treated animals showed a notable depression of various stages of spermatogenesis. The production of spermatids was inhibited by 70.8% in waste-water-treated rats. The populations of spermatogonia, preleptotene spermatocytes and secondary spermatocytes were decreased by 67.2, 71.1 and 73.2%, respectively. The total number of Sertoli cells was affected after waste water treatment. Reduced sperm count and motility resulted in treated groups. A significant fall in the content of various biochemical parameters of reproductive tissues was observed after water treatment.     

Ophthalmic artery color Doppler ultrasonography in mild-to-moderate preeclampsia

OBJECTIVE: To evaluate the hemodynamic changes in mild-moderate preeclampsia using ophthalmic artery Doppler ultrasonography technique. METHODS: Ophthalmic artery pulsatility and resistivity indices were calculated in 30 mild-moderate preeclamptic women and 30 normotensive gravid women of matched gestational age. Student's t-test was performed to test the significance of difference. RESULTS: Both indices of peripheral resistance were found to be significantly lower in the ophthalmic arteries of mild-moderately preeclamptic women than those measured in normotensive gravid women at similar stage of pregnancy. In a small number patients whose disease progressed to severe preeclampsia, both indices increased. CONCLUSION: In patients with mild-moderate preeclampsia, ophthalmic artery color Doppler ultrasonography detects hemodynamic changes that are not present in normotensive gravid women. Reversal of Doppler patterns in a small number of patients with progressive disease supports the hypotheses suggesting the presence of early vasodilation and late vasospasm in the etiology of preeclampsia.     

The evolving role of cytoreductive surgery for metastatic renal cell carcinoma

Metastatic renal cell carcinoma is a devastating disease associated with poor survival. Immunotherapy is the mainstay of treatment, but response rates are low. The role of cytoreductive surgery in the presence of metastatic disease is evolving. From both retrospective and recently published randomized clinical trials, it is now apparent that among patients with metastatic renal cell carcinoma and good performance status, cytoreductive surgery followed by immunotherapy improves survival. However, this approach is likely to be detrimental in patients with poor performance status. Clinical trials of novel agents remain a priority in this disease.     

Vanilloid receptor expression and capsaicin excitation of rat dental primary afferent neurons

Little is known about the molecular mechanisms that cause excitation of neurons which innervate the teeth. We investigated whether rat dental sensory neurons express the vanilloid (capsaicin) receptor (VR1). Dental sensory neurons were identified by retrograde transport of the fluorescent dye DiIC18 placed in maxillary molars. Patch-clamp recordings in culture showed that 65% of DiIC18-labeled rat trigeminal ganglion neurons are excited by capsaicin. Responders covered the entire range of cell sizes examined (soma diameter, 24 to 48 microm). All non-responders had a soma diameter > 33 microm. Capsazepine (1 microM) reduced the capsaicin-evoked membrane current (6/6) and depolarization (7/7 responders). RT-PCR amplified a 375-bp product from DiIC18-labeled neurons which was identical to that expected for VR1. Thus, many rat dental primary afferent neurons are excited by capsaicin, and the response appears to be mediated by VR1. These results suggest that pharmacological blockers of VR1 may provide significant relief of dental pain.