Bradykinin receptors of cerebral microvessels stimulate phosphoinositide turnover.

We examined by ligand binding methods whether bradykinin (BK) receptors exist in rat and pig cerebral microvessels, and in the cerebral cortex from which the microvessels were isolated. We found a high-affinity and saturable BK receptor site in both rat and pig cerebral microvessels, but not in their cerebral cortex. The maximal density of binding and the dissociation constant were 8.0 +/- 4.1 and 6.8 +/- 1.5 fmol/mg of protein and 47 +/- 24 and 150 +/- 8 pM (mean +/- SD) in cerebral microvessels of the pig and rat, respectively. The high-affinity specific binding of BK was effectively displaced by des-Arg0[Hyp3-Thi5-8,D-Phe7]BK, a specific B2 receptor antagonist, but not by des-Arg9[Leu8]BK, a specific B1 antagonist. We also demonstrated that BK increases phosphatidylinositol hydrolysis in cerebral microvessels of the rat and pig. This effect was also blocked by the B2, but not by the B1, antagonist. Increased phosphatidylinositol hydrolysis was manifested by a rapid transient increase in inositol trisphosphate and the later slow accumulation of inositol bisphosphate and inositol monophosphate. Preincubation of microvessels with phorbol ester, stable GTP analogs, pertussis toxin, or in Ca(2+)-free buffer did not influence BK activation of phosphatidylinositol hydrolysis. These results demonstrate the existence of BK receptors of the B2 subtype in brain microvessels, which may play an important role in modulation of the brain microcirculation, probably via increased phosphoinositide turnover.     

Epitope-specific humoral immunity to Plasmodium vivax Duffy binding protein

Erythrocyte invasion by Plasmodium vivax is completely dependent on binding to the Duffy blood group antigen by the parasite Duffy binding protein (DBP). The receptor-binding domain of this protein lies within a cysteine-rich region referred to as region II (DBPII). To examine whether antibody responses to DBP correlate with age-acquired immunity to P. vivax, antibodies to recombinant DBP (rDBP) were measured in 551 individuals residing in a village endemic for P. vivax in Papua New Guinea, and linear epitopes mapped in the critical binding region of DBPII. Antibody levels to rDBP(II) increased with age. Four dominant linear epitopes were identified, and the number of linear epitopes recognized by semi-immune individuals increased with age, suggesting greater recognition with repeated infection. Some individuals had antibodies to rDBP(II) but not to the linear epitopes, indicating the presence of conformational epitopes. This occurred in younger individuals or subjects acutely infected for the first time with P. vivax, indicating that repeated infection is required for recognition of linear epitopes. All four dominant B-cell epitopes contained polymorphic residues, three of which showed variant-specific serologic responses in over 10% of subjects examined. In conclusion, these results demonstrate age-dependent and variant-specific antibody responses to DBPII and implicate this molecule in partial acquired immunity to P. vivax in populations in endemic areas.     

Hypoxia down-regulates placenta growth factor, whereas fetal growth restriction up-regulates placenta growth factor expression: molecular evidence for "placental hyperoxia" in intrauterine growth restriction

Early placental development occurs in an environment of relative hypoxia. Hypoxia promotes angiogenesis and up-regulates vascular endothelial growth factor (VEGF) expression while it down-regulates placenta growth factor (PIGF) that possess 53% homology with VEGF. Morphological studies show poor placental vascular development and an increase in the mitotic index of cytotrophoblasts in intrauterine growth restriction (IUGR). We hypothesized that the reported relatively high oxygen level in the intervillous space in contact with IUGR placental villi will limit angiogenesis by changes in VEGF and PIGF expression and function. Western immunoblot analysis demonstrates a diametric expression of PIGF and VEGF proteins throughout pregnancy with PIGF levels increasing and VEGF levels decreasing, consistent with placental oxygenation. In IUGR placentae, the ratio of PIGF/GAPDH mRNA was increased by 2.3-fold (p < 0.03) and PIGF protein levels were also increased, (p < 0.05) as compared with gestationally-matched normal placentae. PIGF mRNA and protein were localized to the trophoblast bilayer and villous mesenchyme of the human placenta throughout gestation. In vitro studies demonstrated that increasing oxygen tension (hyperoxia) up-regulated PIGF protein in term placental villous explants, whereas hypoxic culture of a term trophoblast choriocarcinoma cell line (BeWo) down-regulated PIGF mRNA and protein and VEGFR-1 (Flt-1) autophosphorylation. The addition of PIGF-1 to a spontaneously transformed first trimester cytotrophoblast cell line stimulated DNA synthesis while PIGF-2 had little effect. VEGF and PIGF exert their biological actions by means of a common receptor VEGFR-1. In the first trimester trophoblast cells, PIGF-1 increased the association of phosphorylated extracellular signal-related kinase (ERK) with VEGFR-1 immunoprecipitates while both PIGF-1 and PIGF-2 also potentiated endogenous VEGF mediated association of phosphorylated extracellular related kinase (ERK) with VEGFR-2 (KDR). More importantly, the addition of PIGF-1 had little effect while PIGF-2 inhibited cell growth in cultured endothelial cells derived from human umbilical vein. Nitric oxide (NO) is reported to promote angiogenesis and PIGF-2 inhibited the basal release of NO from the first trimester trophoblast. The tissue expression and functional studies support the hypothesis of "placental hyperoxia" in early-onset IUGR because hypoxia down-regulates trophoblast PIGF levels, PIGF expression is increased in IUGR, and PIGF-2 inhibits endothelial cell growth. Taken together, these changes provide a cellular explanation for the observed poor angiogenesis in the pathogenesis of IUGR and show that the two PIGF isoforms may modulate trophoblast and endothelial cell function differently, possibly through potentiation of VEGF mediated activation of VEGF-2.     

Effects of the fruit essential oil of Cuminum cyminum Linn. (Apiaceae) on acquisition and expression of morphine tolerance and dependence in mice

The problem of morphine tolerance and dependence is a universal phenomenon threatening social health everywhere the world. The major objective of this paper was to investigate the effects of fruit essential oil (FEO) of Cuminum cyminum on acquisition and expression of morphine tolerance and dependence in mice. Animals were rendered dependent on morphine using the well-established method in which was morphine (50, 50, 75 mg/kg; s.c.) injected three times daily for 3 days. In experimental groups, administration of FEO (0.001, 0.01, 0.1, 0.5, 1 and 2%; 5 ml/kg; i.p.) or Tween-80 (5 ml/kg; i.p.) was performed 60 min prior to each morphine injection (for acquisition) or the last injection of morphine on test day (for expression). Morphine tolerance was measured by tail-flick before and after administration of a single dose of morphine (50 mg/kg; s.c.) in test day (4th day). Morphine dependence was also evaluated by counting the number of jumps after injection of naloxone (5 mg/kg; i.p.) on the test day. The results showed that Cumin FEO, only at the dose of 2%, significantly attenuated the development of morphine tolerance (P < 0.01) and dependence (P < 0.05) while it could be significantly effective on expression of morphine tolerance (1 and 2%) and dependence (0.5, 1 and 2%) in a dose-dependent manner. Solely Cumin FEO injection (0.001–2%) did not show any analgesic effect. In conclusion, the essential oil of Cuminum cyminum seems to ameliorate the morphine tolerance and dependence in mice.     

Evaluating mechanism and severity of injuries among trauma patients admitted to Sina Hospital, the National Trauma Registry of Iran

Purpose: Injuries are one of the leading causes of death and lead to a high social and financial burden. Injury patterns can vary significantly among different age groups and body regions. This study aimed to evaluate the relationship between mechanism of injury, patient comorbidities and severity of injuries. Methods: The study included trauma patients from July 2016 to June 2018, who were admitted to Sina Hospital, Tehran, Iran. The inclusion criteria were all injured patients who had at least one of the following: hospital length of stay more than 24 h, death in hospital, and transfer from the intensive care unit of another hospital. Data collection was performed using the National Trauma Registry of Iran minimum dataset. Results: The most common injury mechanism was road traffic injuries (49.0%), followed by falls (25.5%). The mean age of those who fell was significantly higher in comparison with other mechanisms (p < 0.001). Severe extremity injuries occurred more often in the fall group than in the vehicle collision group (69.0% vs. 43.5%, p < 0.001). Moreover, cases of severe multiple trauma were higher amongst vehicle collisions than injuries caused by falls (27.8% vs. 12.9%, p = 0.003). Conclusion: Comparing falls with motor vehicle collisions, patients who fell were older and sustained more extremity injuries. Patients injured by motor vehicle collision were more likely to have sustained multiple trauma than those presenting with falls. Recognition of the relationship between mechanisms and consequences of injuries may lead to more effective interventions.     

N-nitro- -arginine methylester is protective against ethanol-induced gastric damage in cholestatic rats

In this study the effect of nitric oxide (NO) synthesis inhibition on ethanol-induced gastric damage was evaluated in bile duct-ligated, sham-operated and unoperated rats. The animals were injected intraperitoneally with saline, -arginine (200 mg/kg) or N^G-nitro- -arginine methylester ( -NAME) in doses of 5, 15 and 30 mg/kg, 30 min before ethanol administration. The animals were killed 1 h after ethanol administration and their stomachs were removed for measurement of gastric mucosal damage. The results showed that -NAME significantly enhanced the development of gastric mucosal lesions in sham-operated and unoperated rats, while in bile duct-ligated animals, -NAME decreased and -arginine enhanced the potentiation of ethanol-induced gastric mucosal damage. The plasma level of nitrite and nitrate was also measured and was significantly higher in bile duct-ligated rats than in control groups. The results suggest that inhibition of NO synthase with -NAME has different effects on ethanol-induced gastric damage in cholestatic groups and in normal rats and that these effects can be explained by overproduction of NO in bile duct-ligated animals.     

Iliac vein compression syndrome: a new method of treatment

Iliac vein compression syndrome (May-Thurner syndrome) is caused by compression of the left iliac vein against the pelvic rim by the right iliac artery. Serious vascular sequelae to the leg can result if this is not recognized and corrected in a timely fashion. The condition, often underdiagnosed, is thought to be present in approximately 20 per cent of the adult population. Previously, a major vascular operation with a significant hospital stay was required to correct this compression. As a nonsurgical option, we elected balloon dilation of the stenosed iliac vein, with insertion of a venous stent to maintain the restored lumen. Two patients who had this procedure have been followed for 12 months; venograms show continued patency of the iliac vein with no pressure gradient present. This procedure is safe and cost effective, and it requires a minimal hospital stay.     

Effect of Replacement of Wharton Acellular Jelly With FBS on the Expression of Megakaryocyte Linear Markers in Hematopoietic Stem Cells CD34+

Objective: Animal environments for the growth of stem cells cause the transmission of some diseases and immune problems for the recipient. Accordingly, replacing these environments with healthy environments, at least with human resources, is essential.  One of the media that can be used as an alternative to animal serums is Wharton acellular jelly (AWJ).  Therefore, in this study, we intend to replace FBS with Wharton jelly and investigate its effect on the expression of megakaryocyte-related genes and markers in stem cells. Materials and Methods: In this study, cord blood-derived CD34 positive HSCs were cultured and expanded in the presence of cytokines including SCF, TPO, and FLT3-L. Then, the culture of expanded CD34 positive HSCs was performed in two groups: 1) IMDM culture medium containing 10% FBS and 100 ng / ml thrombopoietin cytokine 2) IMDM culture medium containing 10% AWJ, 100 ng / ml thrombopoietin cytokine.  Finally, CD41 expressing cells were analyzed with the flow cytometry method. The genes related to megakaryocyte lineage including FLI1 and GATA2 were also evaluated using the RT-PCR technique.  Results: The expression of CD41, a specific marker of megakaryocyte lineage in culture medium containing Wharton acellular jelly was increased compared to the FBS group. Additionally, the expression of GATA2 and FLI1 genes was significantly increased related to the control group. Conclusion: This study provided evidence of differentiation of CD34 positive hematopoietic stem cells from umbilical cord blood to megakaryocytes in a culture medium containing AWJ.