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Leila Gobejishvili,1 Walter E Rodriguez,1 Philip Bauer,2 Yali Wang,1 Chirag Soni,2 Todd Lydic,3 Shirish Barve,1 Craig McClain,1 Claudio Maldonado4 1Department of Medicine, School of Medicine, University of Louisville, Louisville, KY, USA; 2Endoprotech, Inc., Louisville, KY, USA; 3Lipidomics Center, Michigan State University, East Lansing, MI, USA; 4Department of Physiology, School of Medicine, University of Louisville, Louisville, KY, USACorrespondence: Claudio Maldonado, Department of Physiology, School of Medicine, University of Louisville, 500 S. Preston Street, HSC A-1115, Louisville, KY, 40292, USA, Tel +1 (502) 852-1078, Email claudio.maldonado@louisville.edu Leila Gobejishvili, Department of Medicine, School of Medicine, University of Louisville, 505 S. Hancock Street, CTR 516, Louisville, KY, 40202, USA, Tel +1 (502) 852-0361, Fax +1 (502) 852-8927, Email l0gobe01@louisville.eduIntroduction: The phosphodiesterase 4 (PDE4) inhibitor, rolipram, has beneficial effects on tissue inflammation, injury and fibrosis, including in the liver. Since rolipram elicits significant CNS side-effects in humans (ie, nausea and emesis), our group developed a fusogenic lipid vesicle (FLV) drug delivery system that targets the liver to avoid adverse events. We evaluated whether this novel liposomal rolipram formulation reduces emesis.Methods: C57Bl/6J male mice were used to compare the effect of three doses of free and FLV-delivered (FLVs-Rol) rolipram in a behavioral correlate model of rolipram-induced emesis. Tissue rolipram and rolipram metabolite levels were measured using LC-MS/MS. The effect of FLVs-Rol on brain and liver PDE4 activities was evaluated.Results: Low and moderate doses of free rolipram significantly reduced anesthesia duration, while the same doses of FLVs-Rol had no effect. However, the onset and duration of adverse effects (shortening of anesthesia period) elicited by a high dose of rolipram was not ameliorated by FLVs-Rol. Post-mortem analysis of brain and liver tissues demonstrated that FLVs affected the rate of rolipram uptake by liver and brain. Lastly, administration of a moderate dose of FLVs-Rol attenuated endotoxin induced PDE4 activity in the liver with negligible effect on the brain.Discussion: The findings that the low and moderate doses of FLVs-Rol did not shorten the anesthesia duration time suggest that FLV delivery prevented critical levels of drug from crossing the blood-brain barrier (BBB) to elicit CNS side-effects. However, the inability of high dose FLVs-Rol to prevent CNS side-effects indicates that there was sufficient unencapsulated rolipram to cross the BBB and shorten anesthesia duration. Notably, a moderate dose of FLVs-Rol was able to decrease PDE4 activity in the liver without affecting the brain. Taken together, FLVs-Rol has a strong potential for clinical application for the treatment of liver disease without side effects.Keywords: liposomes, rolipram, side-effects, PDE4, liver

Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) is one of the important responses of cells to an external stress such as ionizing radiation. We studied radiation-induced NF-kappaB activation in vivo in male BALB/c mice. After the mice were exposed to 8.5 Gy total-body gamma irradiation, the spleen, mesenteric lymph nodes, thymus, liver, lung, colon, brain and bone marrow were harvested 1, 2.5, 5, 10 and 20 h postirradiation. NF-kappaB DNA-binding activity was analyzed in the nuclear protein extracts by a gel shift assay. When compared to the levels in untreated control mice, radiation induced activation of NF-kappaB in spleen, mesenteric lymph nodes and bone marrow but not in the other tissues examined. In contrast, an i.p. injection of a lethal dose (3 mg/kg) of lipopolysaccharide also increased activity of NF-kappaB in the liver and lung. The gel supershift assay with Nfkb1, Rela and/or Rel antibodies revealed that the specific molecular forms of NF-kappaB activated by radiation in the spleen were Nfkb1 homodimers and Nfkb1/Rela heterodimers. In mesenteric lymph nodes, the heterodimerized Rel/Rela NF-kappaB was also activated. In bone marrow, an NF-kappaB-like binding factor was induced that may be Nfkb1/Rela- and Rel/Rela-like heterodimers, but it exhibited a higher mobility than Nfkb1 homodimers. These results indicate that in vivo, ionizing radiation induces NF-kappaB activation that varies in both tissue distribution and moleoular composition.

The issue of sustainability in terms of economic analysis is very important in the present context of regulated brackish water aquaculture. It iswell-known that ecological imbalances are the cause of reduced productivity and profitability. In the present investigation, the economic indicators such as shrimp productivity per unit of major inputs, cost of input per unit cost of output, amount of major inputs per unit of land area, net returns, returns to operator's labour and management, return to capital and management, rate of return on capital investment, ratio of net profit to operating cost, payback period, break-even price and break-even production for crop I and crop II of shrimp ponds located near Uran in Raigad district of Maharashtra were studied. Rate of return determines the operational efficiency of shrimp culture. The rate of return on capital investment was in the range of 51.81-65.30%), while the pay back period was 2.0-2.74 years. Lowest break-even price was Rs 179.48-185.32 kg-1 in crop II while highest of Rs. 258.80-261.30 kg-1 in crop I. The break-even price indicates minimum price of shrimp for sale at given production level. The break-even production was lowest (718.16-719.25 kg ha-1) in crop I and highest (911.13-921.05 kg ha-1) in crop II. Comparative economic study of crops indicated that economic performance of Crop II was better than that of Crop I. [ABSTRACT FROM AUTHOR]

Hypobaric hypoxia at high elevation represents an important physiological stressor for montane organisms, but optimal physiological strategies to cope with hypoxia may vary among species with different life histories. Montane birds exhibit a range of migration patterns; elevational migrants breed at high elevations but winter at low elevations or migrate further south, while high-elevation residents inhabit the same elevation throughout the year. Optimal physiological strategies to cope with hypoxia might therefore differ between species that exhibit these two migratory patterns, because they differ in the amount time spent at high elevation. We examined physiological parameters associated with blood-oxygen transport (haemoglobin concentration and haematocrit, i.e. the proportion of red blood cells in blood) in nine species of elevational migrants and six species of highelevation residents that were sampled along a 2200 m (1000-3200 m) elevational gradient. Haemoglobin concentration increased with elevation within species regardless of migratory strategy, but it was only significantly correlated with haematocrit in elevational migrants. Surprisingly, haemoglobin concentration was not correlated with haematocrit in high-elevation residents, and these species exhibited higher mean cellular haemoglobin concentration than elevational migrants. Thus, alternative physiological strategies to regulate haemoglobin concentration and blood O2 carrying capacity appear to differ among birds with different annual elevational movement patterns. [ABSTRACT FROM AUTHOR]

The effects of Cognitive Behaviour Therapy (CBT) on social anxiety have been well documented in scientific literature. A 19 year old girl hailing from upper middle socioeconomic status nuclear family, with professionally qualified parents, and no significant family history or past history, temperamentally quiet and shy, presented with symptoms of feeling extremely anxious with people around her, except her parents, leading to severe forms of avoidance behaviours, treatment at various places having yielded mixed and temporary results. CBT was used for this purpose, Behavior Therapy (BT) techniques like time scheduling, relaxation techniques, Systematic Desensitization(SD), in vivo exposure to social situations with co therapist, were used along with identification of errors, thought restructuring techniques, and psycho education about the problem as it has been chronic and the client was unable to comprehend it fully. Minimal dose of antidepressants was ongoing since several years. Treatment yielded positive results until client started reporting fleeting delusional symptoms intermittently. Psycho diagnostic assessment confirmed psychotic symptomatology of a delusional nature. Medication was started for the same. After an adequate period of medication, CBT was restarted and client responded well. Currently client has made a great deal of progress in terms of joining up for classes to learn new things, joining up for a regular college to finish her studies, client is also doing academically well there. Client has made new acquaintances, as well as a close friend in college. Treatment period lasted for over 2 years, and follow up is ongoing. Client continues to have anxious feelings while meeting new people, but tends to feel better in a short span of time, as against earlier. [ABSTRACT FROM AUTHOR]