GABAergic Interneurons at Supraspinal and Spinal Levels Differentially Modulate the Antinociceptive Effect of Nitrous Oxide in Fischer Rats

Background: The study hypothesizes that nitrous oxide (N2O) releases opioid peptide in the brain stem, which results in inhibition of [gamma]-aminobutyric acid-mediated (GABAergic) neurons that tonically inhibit the descending noradrenergic inhibitory neurons (DNIN), resulting in activation of DNIN. In the spinal cord, activation of DNIN leads to the release of norepinephrine, which inhibits nociceptive processing through direct activation of [alpha]2 adrenoceptor and indirect activation of GABAergic neurons through [alpha]1 adrenoceptor. Arising from this hypothesis, it follows that GABAergic neurons will modulate the antinociceptive effect of N2O in diametrically opposite directions at supraspinal and spinal levels. The authors have tested this tenet and further examined the effect of midazolam, a GABA-mimetic agent, on N2O-induced antinociceptive effect.

Methods: Adult male Fischer rats were administered muscimol (GABAA receptor agonist) intracerebroventricularly (icv), gabazine (GABAA receptor antagonist) intrathecally (intrathecal), or midazolam intraperitoneally (intraperitoneal). Fifteen minutes later, they were exposed to air or 75% N2O and were subjected to the plantar test after 30 min of gas exposure. In some animals administered with midazolam, gas exposure was continued for 90 min, and the brain and spinal cord were examined immunohistochemically.

Results: The N2O-induced antinociceptive effect, which was attenuated by icv muscimol, intrathecal gabazine, and intraperitoneal midazolam. Midazolam inhibited N2O-induced c-Fos expression (a marker of neuronal activation) in the pontine A7 and spinal cord.     

Absence of hydrocarbon-induced nephropathy in rats exposed subchronically to volatile hydrocarbon mixtures pertinent to gasoline

Ninety-day inhalation studies were conducted on 50:50 weight percent (wt %) mixtures of n-butane:n-pentane and isobutane:isopentane, respectively, and on a distillation cut boiling below 145 degrees F of a reference unleaded gasoline blend to assess the nephrotoxicity of these volatile mixtures. The mixtures of butanes and pentanes were selected because these four hydrocarbons are the most prevalent components of gasoline vapors encountered under typical occupational exposures. The 0-145 degrees F gasoline distillation fraction was tested because it reasonably approximates the composition of gasoline vapors measured under occupational settings. Male and female F-344 rats were exposed to 2 levels of each mixture, 6 hours per day, 5 days per week, for 13 weeks. The target concentrations for the butane:pentane mixtures were 4500 and 1000 parts per million (ppm), while 5200 and 1200 ppm were set for the gasoline distillation fraction. An interim sacrifice was conducted after 28 days. The rats were not significantly affected by the exposures, and there was no evidence of hydrocarbon-induced nephropathy in either sex at the termination of each study. However, at the 28-day interim sacrifice period for both butane:pentane mixtures, mild, transient treatment-related but not exposure-related kidney effects were observed in the male rats. These perturbations were absent at the interim sacrifice period for the gasoline distillation fraction.     

Characterization of NK cells and extrathymic T cells generated in the liver of irradiated mice with a liver shield

We previously reported that c-kit⁺ stem cells which give rise to extrathymic T cells are present in the liver of adult mice. Further characterization of extrathymic T cells in the liver of adult mice is conducted here. When mice with a liver shield were lethally (9.5 Gy) irradiated, all mice survived. All tested organs showed a distribution pattern of hepatic lymphocytes on day 7. The distribution pattern in the liver was characterized by an abundance of NK (CD3^? IL-2Rβ⁺) and extrathymic T cells (CD3^int IL-2Rβ⁺) before and after irradiation. To determine their function, post-irradiation allogeneic bone marrow transplantation (BMT) was performed in mice with or without a liver shield. Allogeneic BM cells were rejected in mice with a liver shield and specific activation of CD8⁺ CD3^int IL-2Rβ⁺ cells was induced. At that time, potent cytotoxicity of liver mononuclear cells (MNC) against allogeneic thymocytes was induced. Both NK1.1⁺ and NK1.1^? subsets of CD3^int cells expanded in these mice. An in vivo elimination experiment of the subsets indicated that the NK1.1⁺ subset of CD3^int cells (i.e. NK T cells) was much more associated with the rejection of allogeneic BM cells. However, even after the elimination of NK T cells, allogeneic BM cells were rejected. In this case, granulocytes expanded in parallel with NK1.1^? subsets. Granulocytes may also be associated with the rejection of allogeneic BM cells. These results suggest that the liver is an important haematopoietic organ even in adult life.     

Cytokines in the stools of children with complicated shigellosis.

The pathogenesis of the systemic complications, leukemoid reaction and hemolytic uremic syndrome, associated with Shigella dysenteriae type 1 infection is not well understood. The excessive production of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), has been suggested as a possible factor. We measured IL-6 and TNF-alpha in stools of 56 children with S. dysenteriae 1 infection and 29 children without any apparent infection, all age 12 to 60 months. Sixteen children with S. dysenteriae 1 infection had leukemoid reaction or hemolytic uremic syndrome (complicated shigellosis), while the others did not (uncomplicated shigellosis). Stool IL-6 and TNF-alpha concentrations were higher in children with uncomplicated shigellosis than in children with complicated shigellosis (P = 0.009 and < 0.001, respectively) or in uninfected children (P < 0.001). It is concluded that complicated infection is not associated with higher concentrations of the proinflammatory cytokines IL-6 and TNF-alpha in stool.     

Bivalent non-typhoidal Salmonella outer membrane vesicles immunized mice sera confer passive protection against gastroenteritis in a suckling mice model

Invasive non-typhoidal Salmonella (iNTS) serovars, especially Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE), cause gastroenteritis worldwide. Due to the emergence of multi-drug resistance in iNTS, a broad-spectrum vaccine is urgently needed for the prevention of iNTS infection. Currently, there is no effective licensed vaccine against iNTS available in the market. We have formulated an outer membrane vesicles (OMVs) based bivalent immunogen as a vaccine candidate to generate broad-spectrum protective immunity against both recently circulating prevalent ST and SE. We have isolated OMVs from ST and SE and formulated the immunogen by mixing both OMVs (1:1 ratio). Three doses of bivalent immunogen significantly induced humoral immune responses against lipopolysaccharides (LPSs) and outer membrane proteins (OMPs) as well as a cell-mediated immune response in adult mice. We also observed that proteins of OMVs act as an adjuvant for generation of high levels of anti-LPS antibodies through T cell activation. We then characterized the one-day old suckling mice model for both ST and SE mediated gastroenteritis and used the model for a passive protection study. In the passive protection study, we found the passive transfer of bivalent OMVs immunized sera significantly reduced ST and SE mediated colonization and gastroenteritis symptoms in the colon of suckling mice compared to non-immunized sera recipients. The overall study demonstrated that OMVs based bivalent vaccine could generate broad-spectrum immunity against prevalent iNTS mediated gastroenteritis. This study also established the suckling mice model as a suitable animal model for vaccine study against iNTS mediated gastroenteritis.     

Nutritional status of pavement dweller children of Calcutta City

Pavement dwelling is likely to aggravate malnutrition among its residents due to extreme poverty, lack of dwelling and access to food and their exposure to polluted environment. Paucity of information about nutritional status of street children compared to that among urban slum dwellers, squatters or rural/tribal population is quite evident. The present study revealed the magnitude of Protein Energy Malnutrition (PEM) and few associated factors among a sample of 435 underfives belonging to pavement dweller families and selected randomly from clusters of such families, from each of the five geographical sectors of Calcutta city. Overall prevalence of PEM was found almost similar (about 70%) to that among other 'urban poor' children viz. slum dwellers etc., but about 16% of them were found severely undernourished (Grade III & V of IAP classification of PEM). About 35% and 70% of street dweller children had wasting and stunting respectively. Severe PEM (Grade III & IV) was more prevalent among 12-23 months old, girl child, those belonged to illiterate parents and housewife mothers rather than wage earners. It also did increase with increase of birth rate of decrease of birth interval.     

Carcinoma of the penis metastasizing to the dorsal spine. A case report

Carcinoma of the penis tends to have a predictable route of spread by direct invasion and by regional lymphatic involvement to the inguinal group of lymph nodes. Blood-borne distant spread is rare, last to occur, and is seen in 1-3% of cases. Metastasis to the spine is even rarer. We encountered one such case who presented with spinal metastasis, as documented by the whole body bone scan, and this was later followed by involvement of the inguinal nodes. This case is unique in its site of metastatic presentation as well as its pattern of presentation.