Induction of indolamine 2,3-dioxygenase in primary human macrophages by human immunodeficiency virus type 1 is strain dependent

Increased kynurenine pathway metabolism has been implicated in the etiology of AIDS dementia complex (ADC). The rate-limiting enzyme for this pathway is indolamine 2,3-dioxygenase (IDO). We tested the efficacy of different strains of human immunodeficiency virus type 1 (HIV1-BaL, HIV1-JRFL, and HIV1-631) to induce IDO in cultured human monocyte-derived macrophages (MDM). A significant increase in both IDO protein and kynurenine synthesis was observed after 48 h in MDM infected with the brain-derived HIV-1 isolates, laboratory-adapted (LA) HIV1-JRFL, and primary isolate HIV1-631. In contrast, almost no kynurenine production or IDO protein was evident in MDM infected with the highly replicating macrophage-tropic LA strain HIV1-BaL. The induction of IDO and kynurenine synthesis by HIV1-JRFL and HIV1-631 declined to baseline levels by day 8 postinfection. Abundant HIV-1 replication did not reduce the ability of exogenous gamma interferon (IFN-gamma) to induce IDO and kynurenine synthesis in HIV-infected MDM. The addition of anti-IFN-gamma antibody to MDM infected with HIV1-JRFL resulted in an absence of detectable IDO protein after 48 h and a decrease of 64% +/- 1% in supernatant kynurenine concentration. Together, these results indicate that only selected strains of HIV-1 are capable of inducing IDO synthesis and subsequent kynurenine metabolism in MDM. The induction of IDO, while apparently independent of replication capacity, appears to be mediated by a transient production of IFN-gamma in MDM responding to the initial infection with selected strains of HIV-1.     

Biological effects of active fraction isolated from Hydnocarpus pentandra (Bunch. –Ham.) Oken seeds against Helicoverpa armigera (Hub.) (Lepidoptera: Noctuidae)

Hexane, chloroform, ethyl acetate and methanol extracts of Hydnocarpus pentandra (Flacourtiaceae) seeds were tested for antifeedant, larvicidal, pupal mortality and adult deformations activities against Helicoverpa armigera. Crude extracts were screened at 0.5, 1.0, 1.5 and 2.0% concentrations. Bioassay-guided fractionation method was followed to isolate the active fraction from the crude extract. Active fraction was analysed by FT-IR, ¹H NMR, ¹³C NMR and GC-MS. Hexane extract presented the highest antifeedant (87.89%), pupal mortality (41.67%) and adult malformation activities at 2% concentration. Seven different fractions were isolated from hexane extract, among which fraction-2 showed the highest antifeedant (81.43%) activity and recorded the lowest LC₅₀ of 792.07 ppm. The fraction-2 contained two cyclopentenyl carboxylic acids, such as hydnocarpic acid (1) and chaulmoogric acid (2) in the ratio of 2:1. These compounds were major constituents in the active fraction of hexane extract of H. pentandra seeds. Fraction-2 can be used for agricultural pest management.     

Alteration in some pro and anti-inflammatory cytokines associated with complete and incomplete gestation cycle of cows

The maternal immune response during pregnancy is regulated by a complex array of pro and anti-inflammatory cytokines which provide optimum conditions for the embryo implantation and survival. The possible role of pro and anti-inflammatory cytokines during the complete gestation cycle of ruminants and the difference in their circadian rhythmicity between successful and unsuccessful pregnancies is still unknown. To study this, blood samples were collected from three groups of cows, pregnant (P), non-pregnant (NP) and aborted (ABORT) cows starting from the day of Artificial Insemination (AI) till calving in P cows and till stages of non pregnancy in other cows. Various pro and anti-inflammatory cytokines were estimated by bovine-specific ELISA test and compared. Successful pregnancies had lower levels of pro-inflammatory cytokines (IL-2, IL-6 and IL-8) but higher anti-inflammatory cytokine (IL-10) mainly during implantation. Significant (p < 0.05) increase in pro-inflammatory cytokines and low IL-10 levels was noticed at abortion and at calving. This study indicates that temporal and spatial aspects of reducing the release of various pro-inflammatory cytokines and maintaining high anti-inflammatory cytokines during pregnancy are essentially required for maintenance of pregnancy. Any disturbance in the cytokine equilibrium may lead to persistent inflammation and pregnancy failure.     

Fluctuation in the number,type and activity of blood neutrophils in cows exhibiting successful and unsuccessful completion of gestation cycle

Neutrophils (first line of cellular defense) are capable of detecting presence of foreign genome in the mother’s womb. Role of neutrophils during full gestation cycle of ruminants and the difference in their number, type, and activity in successful and unsuccessful pregnancies is not known. To evaluate this, blood samples were collected at artificial insemination (0 day) and on days 10, 14, 16, 18, and 21 in non-pregnant (NP) cows. However in pregnant (P) cows, samples were collected as indicated above and every 30 days for the complete gestation. In aborted cows, samples were collected as above till abortion. Higher total leukocyte counts were observed in NP and aborted cows at abortion. Neutrophil: lymphocyte ratio increased significantly (p < 0.05) in NP and aborted cows. Phagocytic activity (PA) and myeloperoxidase concentrations were significantly higher (p < 0.05) on day 18 post insemination in NP cows. PA and myeloperoxidase also increased significantly (p < 0.05) at abortion in aborted cows. Neutrophils exhibited limited decrease in their number and activity in successful pregnancies during implantation. After that their number and activity were constantly maintained throughout the gestation cycle. Any increase in the number and inflammatory activity of neutrophils may lead to non-pregnancy or loss in pregnancy.     

荒漠沙蜥繁殖生态研究

荒漠沙蜥（Ｐｈｒｙｎｏｃｅｐｈａｌｕｓｐｒｚｅｗａｌｓｋｉｉ）１年繁殖１次,有明显的季节性周期。４月初出蛰时雄性精巢已相当发育,５月其重量和体积最大,６月变小,进入精子发生的晚期,７月降到最小,８月开始回升,１０月中旬入蛰时已接近春季出蛰时水平。１年内仅７月精巢中无精子。雌性出蛰后卵细胞开始发育,４月下旬进入成熟期,６月达高峰,７月下降,８月进入休止期。每雌年产卵１～３枚或１～４枚,平均１．８３（ｎ＝４８,１９８７）和２．１７（ｎ＝４８,１９９３）。特定体长组的生殖率是影响种群年平均生殖率的主要因素。生殖周期与光周期相符,光周期是影响荒漠沙蜥生殖周期的主要气候因子。     

New insights on the potential anti-epileptic effect of metformin: Mechanistic pathway

Epilepsy is a chronic neurological disease characterized by recurrent seizures. Epilepsy is observed as a well-controlled disease by anti-epileptic agents (AEAs) in about 69%. However, 30%–40% of epileptic patients fail to respond to conventional AEAs leading to an increase in the risk of brain structural injury and mortality. Therefore, adding some FDA-approved drugs that have an anti-seizure activity to the anti-epileptic regimen is logical. The anti-diabetic agent metformin has anti-seizure activity. Nevertheless, the underlying mechanism of the anti-seizure activity of metformin was not entirely clarified. Henceforward, the objective of this review was to exemplify the mechanistic role of metformin in epilepsy. Metformin has anti-seizure activity by triggering adenosine monophosphate-activated protein kinase (AMPK) signalling and inhibiting the mechanistic target of rapamycin (mTOR) pathways which are dysregulated in epilepsy. In addition, metformin improves the expression of brain-derived neurotrophic factor (BDNF) which has a neuroprotective effect. Hence, metformin via induction of BDNF can reduce seizure progression and severity. Consequently, increasing neuronal progranulin by metformin may explain the anti-seizure mechanism of metformin. Also, metformin reduces α-synuclein and increases protein phosphatase 2A (PPA2) with modulation of neuroinflammation. In conclusion, metformin might be an adjuvant with AEAs in the management of refractory epilepsy. Preclinical and clinical studies are warranted in this regard.