Synthesis of some tropane derivatives of anticipated activity on the reuptake of norepinephrine and/or serotonin

A variety of tropane derivatives 14a–g were prepared via the reaction of the alcohol analogs 12a and 12b with substituted fluorobenzenes 13a–f. The prepared compounds were tested for their activity and selectivity toward the norepinephrine transporter (NET) and serotonin transporter (SERT) using yohimbine-induced mortality and 5-hydroxytryptophan-induced neurotoxicity in mice, respectively. All the tested compounds were found to be NE and 5-HT reuptake inhibitors except 14d which exhibited selective 5-HT reuptake inhibition activity.     

Induction of indoleamine 2,3-dioxygenase in vascular smooth muscle cells by interferon-gamma contributes to medial immunoprivilege

Atherosclerosis and graft arteriosclerosis are characterized by leukocytic infiltration of the vessel wall that spares the media. The mechanism(s) for medial immunoprivilege is unknown. In a chimeric humanized mouse model of allograft rejection, medial immunoprivilege was associated with expression of IDO by vascular smooth muscle cells (VSMCs) of rejecting human coronary artery grafts. Inhibition of IDO by 1-methyl-tryptophan (1-MT) increased medial infiltration by allogeneic T cells and increased VSMC loss. IFN-gamma-induced IDO expression and activity in cultured human VSMCs was considerably greater than in endothelial cells (ECs) or T cells. IFN-gamma-treated VSMCs, but not untreated VSMCs nor ECs with or without IFN-gamma pretreatment, inhibited memory Th cell alloresponses across a semipermeable membrane in vitro. This effect was reversed by 1-MT treatment or tryptophan supplementation and replicated by the absence of tryptophan, but not by addition of tryptophan metabolites. However, IFN-gamma-treated VSMCs did not activate allogeneic memory Th cells, even after addition of 1-MT or tryptophan. Our work extends the concept of medial immunoprivilege to include immune regulation, establishes the compartmentalization of immune responses within the vessel wall due to distinct microenvironments, and demonstrates a duality of stimulatory EC signals versus inhibitory VSMC signals to artery-infiltrating T cells that may contribute to the chronicity of arteriosclerotic diseases.     

Seasonal allocation of carbohydrates between above‐ and below‐ground organs of Typha domingensis

Seasonal carbohydrates allocation by Typha domingensis was evaluated to identify the potential physiological weaknesses in the growth cycle of this plant in Lake Burullus, Egypt. Monthly plant samples (February–October 2014) were separated into shoots, roots and rhizomes to evaluate the seasonal changes in water‐soluble carbohydrates (WSC), starch and total non‐structural carbohydrates (TNC) for each plant organ. The present study indicated that rhizomes are strong carbohydrates sink during the life cycle of T. domingensis. Starch represented the greatest part of the TNC pool, surpassing the concentration of WSC 1.8–4.3 times. The WSC, starch and TNC concentrations of T. domingensis below‐ground organs (rhizomes and roots) were high at the beginning of the vegetative period (February); they reached their minima in March to support the shoots growth, then were followed by a gradual increase due to the translocation from shoots. The time when T. domingensis is expected to be most susceptible to a management technique is at the point in the seasonal cycle when the stored carbohydrates are at the lowest (in March).     

Plasma and urinary selenium in Saudi Arabian patients with dilated cardiomyopathy

We measured selenium (Se) levels in the urine and blood plasma samples of 72 Saudi Arabian patients with dilated cardiomyopathy (DCM) and 70 control subjects of the same origin. To correct for differences in the hydration state of the subjects, the selenium concentration for each urine sample was normalized by dividing it by the concentration of creatinine (CREAT) in the same sample. The median (and range) of the values found for the concentration of Se in plasma, urine, and normalized concentration in urine for the control subjects was 1.306 (0.66–2.50) μM, 0.478 (0.05–2.00) μM, and 56.7 (10.6–426.5) μM Se/M CREAT, respectively, whereas, for the patients, it was 1.246 (0.53–2.45) μM, 0.39 (0.05–1.90) μM, and 75.1 (4.9–656.2) μM Se/M CREAT, respectively. Additionally, the patients were separated into three subgroups according to the severity of their disease state as judged by NYHA procedure, and were then compared to the control group. Only group 4 (the most severe state of the disease) had a significantly lower concentration of urinary Se than the control group. However, the difference became nonsignificant when normalized for CREAT levels. There was no significant difference in the plasma Se levels between the controls and any of the patient groups. As the plasma Se in the control group and in the DCM patients both fell on the low end of the “normal” range, with the patients being marginally lower than the controls, there is no firm evidence from this study to suggest that Se is related to the high incidence rate of DCM found in Saudi Arabia.     

ST-1, a 39-kilodalton protein in Trypanosoma brucei, exhibits a dual affinity for the duplex form of the 29-base-pair subtelomeric repeat and its C-rich strand.

In our attempt to identify telomere region-binding proteins in Trypanosoma brucei, we identified ST-1, a polypeptide with novel features. ST-1 was chromatographically purified from S-100 cell extracts and was renatured from a sodium dodecyl sulfate-protein gel as a 39-kDa polypeptide. It forms a specific complex with the trypanosome telomere repeats of TTAGGG, but more significantly, it shows a higher affinity for the 29-bp subtelomere repeats of T. brucei. These 29-mer boxes are a large tandem series of telomere-derived repeats which separate the simple telomere DNA from middle-repetitive telomere-associated sequences on many chromosomes. ST-1 is the first example of a protein binding within such large repetitive subtelomere elements in trypanosomes or other organisms. ST-1 is also novel in that it has a selective affinity for the C-rich strands of both the subtelomeric 29-mer and the telomere repeats, comparable to that for the duplex form of the respective repeats. All previously described telomere-binding proteins have affinity for only the duplex form or for the G-rich strand. This C-rich strand binding specificity of ST-1 may provide insight into this protein's mechanism of binding in vivo.     

alpha-1-Anti-trypsin, an inhibitor of renin.

A naturally occurring competitive inhibitor of pig kidney renin has been identified in human plasma. The inhibitor was shown to be alpha-1 anti-trypsin and the effect in vitro on the renin activity was examined. The slope in the Hill plot is compatible with the assumption of one-site competitive inhibition. Other proteinase inhibitors, such as alpha-2-macroglobulin and C1 inactivator, however, have no inhibitory effect on the renin-angiotensinogen reaction.     

Follow-up Study of Physical Growth of Children Who Had Excessive Weight Gain in First Six Months of Life

The aim of this study was to determine whether excessive weight gain in the first six weeks, three months, or six months of life was correlated. with overweight and obesity at the age of 6 to 8 years. One hundred and thirty eight infants with excessive weight gain in the first six months of life, 53 children with slow weight gain, and 33 children with an average weight gain were re-examined at the age of 6, 7, or 8 years.The mean height and weight of children who had gained weight rapidly in infancy were significantly higher than those of children who had gained weight slowly; those of infants whose weight gain had been average fell in between. The number of obese children in the rapid-weight-gain group was significantly higher than that of the combined average and slow-weight-gain groups. The rapidity of weight gain in infancy was a better guide to the risk of overweight in later childhood than the weight of the parents.