Comparison of Paravertebral Block with Conventional Spinal Anesthesia in Patients Undergoing Unilateral Inguinal Hernia Repair.

CONTEXT: Although spinal anesthesia (also known as subarachnoid block [SAB]) is used widely for inguinal hernia repair, the paravertebral block (PVB) that produces unilateral, segmental analgesia is used with a high success rate in inguinal hernia repair. AIMS: The aim of the study was to compare SAB and PVB in inguinal hernia repair, in terms of the duration of postoperative analgesia and adverse events. SETTINGS AND DESIGN: This was a prospective, randomized, controlled double-blind study. METHODS: This study was done on 60 male patients of American Society of Anesthesiology (ASA) I and II. Patients were categorized into 30 in each group, either to receive PVB block at two levels T10 and L1 using 15 mL and 5 mL of 0.5% bupivacaine and 1 µg.kg-1 of buprenorphine or SAB with 12.5 mg of 0.5% hyperbaric bupivacaine injected intrathecally. STATISTICAL ANALYSIS USED: SPSS 18.0 and R version 3.2.2 were used for analyzing the data. Categorical measurements were presented in number (%) and analyzed using Chi-square/Fischer's exact test. Continuous measurements were analyzed using Student's t-test. RESULTS: Age, weight, height, and ASA status were comparable in both the groups. In the PVB group, eight patients had failure of block. Hemodynamic responses, time to first analgesia and ambulation, time required to perform the block, Bromage score, satisfaction score, failure rate, and intra- and postoperative drugs used showed a statistically significant difference between the groups (P < 0.001). CONCLUSION: PVB is not a sole anesthetic technique due to a higher failure rate and increased intraoperative fentanyl requirement but has advantages such as prolonged analgesia, stable hemodynamics, and early ambulation.

Evaluation of rabies virus neutralizing antibody titres induced by intramuscular inoculation of rabies DNA vaccine in mice and Bonnet monkeys (Macaca radiata).

A rabies DNA vaccine consisting of plasmid DNA expressing the rabies virus surface glycoprotein was injected (im) twice at two week interval to outbred swiss mice or Bonnet monkeys (Macaca radiata) and the levels of rabies virus neutralizing antibody (VNA) titres were examined over a one year period. In mice, the VNA titre was maintained above the minimum protective level (0.5 I.U./ml) up to 10 months after primary immunization, while in monkeys, the titre dropped below the protective level by 6 months. An anamnestic B cell response was seen in both mice and monkeys following the administration of a booster dose, 10 and 6 months after the primary immunization, respectively. These results indicate that im injection of rabies DNA vaccine induces VNA in nonhuman primates and mice unlike intradermal (id) immunization, which was shown to induce VNA only in mice but not in monkeys. This is the first report on the induction of VNA in nonhuman primates by im inoculation of rabies DNA vaccine.

Serine 27, a human retinoid X receptor alpha residue, phosphorylated by protein kinase A is essential for cyclicAMP-mediated downregulation of RXRalpha function.

Retinoid X Receptor alpha (RXRalpha), a member of the steroid-thyroid hormone receptor super family, is phosphorylated in vitro by protein kinase A (PKA) and this phosphorylation is inhibited in presence of PKA inhibitory peptide. Analysis of various deletion mutants of RXRalpha indicate that the amino-terminal A/B domain is the target for PKA phosphorylation. An RXRalpha mutant in which serine residue 27 is mutated to alanine is no longer phosphorylated by PKA. In vivo transfection experiments in COS cells indicate that cyclic AMP represses retinoic acid-mediated transcriptional activation of RXRalpha and this repression is mediated by serine 27. These results indicate that serine 27 of RXRalpha is an unique target for phosphorylation by PKA in vitro and it has an important role in the crosstalk between RXRalpha and cyclic AMP signalling pathways.

Immunization with plasmid DNA encoding the envelope glycoprotein of Japanese Encephalitis virus confers significant protection against intracerebral viral challenge without inducing detectable antiviral antibodies.

A plasmid DNA construct, pCMXENV encoding the envelope (E) glycoprotein of Japanese Encephalitis virus (JEV), was constructed. This plasmid expresses the E protein intracellularly, when transfected into Vero cells in culture. The ability of pCMXENV to protect mice from lethal JEV infection was evaluated using an intracerebral (i.c.) JEV challenge model. Several independent immunization and JEV challenge experiments were carried out and the results indicate that 51 and 59% of the mice are protected from lethal i.c. JEV challenge, when immunized with pCMXENV via intramuscular (i.m.) and intranasal (i.n.) routes respectively. None of the mice immunized with the vector DNA (pCMX) survived in any of these experiments. JEV-specific antibodies were not detected in pCMXENV-immunized mice either before or after challenge. JEV-specific T cells were observed in mice immunized with pCMXENV which increased significantly after JEV challenge indicating the presence of vaccination-induced memory T cells. Enhanced production of interferon-gamma (IFN-gamma) and complete absence of interleukin-4 (IL-4) in splenocytes of pCMXENV-immunized mice on restimulation with JEV antigens in vitro indicated that the protection is likely to be mediated by T helper (Th) lymphocytes of the Th1 sub-type. In conclusion, our results demonstrate that immunization with a plasmid DNA expressing an intracellular form of JEV E protein confers significant protection against i.c. JEV challenge even in the absence of detectable antiviral antibodies.

Non-viral ex vivo hepatic gene transfer by in situ lipofection of liver and intraperitoneal transplantation of hepatocytes.

Perfusion of liver with plasmid DNA-lipofectin complexes via the portal vein results in efficient accumulation of the vector in hepatocytes. Such hepatocytes, when administered intraperitoneally into a hepatectomized rat, repopulate the liver and express the transgene efficiently. This procedure obviates the need for large-scale hepatocyte culture for ex vivo gene transfer. Further, intraperitoneal transplantation is a simple and cost-effective strategy of introducing genetically modified hepatocytes into liver. Thus, in situ lipofection of liver and intraperitoneal transfer of hepatocytes can be developed into a novel method of non-viral ex vivo gene transfer technique that has applications in the treatment of metabolic disorders of liver and hepatic gene therapy.