Quantification of 5-HT1A and 5-HT2A receptor Binding in Depressed Suicide Attempters and Non-Attempters

Objective: To determine serotonin system abnormalities related to major depression or previous suicidal behavior.

Methods: [¹¹C]WAY100635, [¹⁸F]altanserin and positron emission tomography were used to compare 5-HT_1A and 5-HT_2A binding in MDD patients divided into eight past suicide attempters (>4yrs prior to scanning) and eight lifetime non-attempters, and both groups were compared to eight healthy volunteers.

Results: The two receptor types differed in binding pattern across brain regions from each other, but there were no differences in binding between healthy volunteers and the two depressed groups or between depressed suicide attempters and non-attempters. No effects of depression severity or lifetime aggression were observed for either receptor.

Conclusion: Limitations of this study include small sample size and absence of high lethality suicide attempts in the depressed attempter group. No trait-like binding correlations with past suicide attempt or current depression were observed. Given the heterogeneity of nonfatal suicidal behavior, a larger sample study emphasizing higher lethality suicide attempts may find the serotonin biological phenotype seen in suicide decedents.     

Lymphoid Neogenesis in Murine Cardiac Allografts Undergoing Chronic Rejection

Lymphoid neogenesis is the process by which ectopic lymphoid accumulations that resemble lymph nodes arise in nonlymphoid tissues. Such lymphoid accumulations, known as tertiary lymphoid organs (TLO), are observed in chronic autoimmunity and they propagate immune pathology by setting up local antigen presenting sites. Whether lymphoid neogenesis occurs in transplanted organs and contributes to rejection is not well understood. To begin to address this question, we retrospectively analyzed 319 murine cardiac allografts for microscopic evidence of lymph-node-like structures. We found 78 allografts that had either classical TLO, characterized by discrete T- and B-cell zones and high endothelial venules (HEV) expressing peripheral node addressin (PNAd) (n = 34), or PNAd(+) HEV without organized lymphoid accumulations (n = 44). These changes were present in both short- and long-lived allografts and were invariably associated with rejection. Importantly, they occurred in 78% of allografts undergoing chronic rejection (n = 85) but in only 7% of allografts undergoing primarily acute rejection (n = 184). These findings indicate that, like autoimmunity, alloimmunity is associated with lymphoid neogenesis in the target organ and suggest a role for local T-cell activation in chronic allograft rejection.     

The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation.

Lowering of the elevated plasma FFA concentration in 18- 24-h fasted rats with nicotinic acid (NA) caused complete ablation of subsequent glucose-stimulated insulin secretion (GSIS). Although the effect of NA was reversed when the fasting level of total FFA was maintained by coinfusion of soybean oil or lard oil (plus heparin), the more saturated animal fat proved to be far more potent in enhancing GSIS. We therefore examined the influence of individual fatty acids on insulin secretion in the perfused rat pancreas. When present in the perfusion fluid at 0.5 mM (in the context of 1% albumin), the fold stimulation of insulin release from the fasted pancreas in response to 12.5 mM glucose was as follows: octanoate (C8:0), 3.4; linoleate (C18:2 cis/cis), 5.3; oleate (C18:1 cis), 9.4; palmitate (C16:0), 16. 2; and stearate (C18:0), 21.0. The equivalent value for palmitoleate (C16:1 cis) was 3.1. A cis--> trans switch of the double bond in the C16:1 and C18:1 fatty acids had only a modest, if any, impact on their potency. A similar profile emerged with regard to basal insulin secretion (3 mM glucose). When a subset of these fatty acids was tested in pancreases from fed animals, the same rank order of effectiveness at both basal and stimulatory levels of glucose was seen. The findings reaffirm the essentiality of an elevated plasma FFA concentration for GSIS in the fasted rat. They also show, however, that the insulinotropic effect of individual fatty acids spans a remarkably broad range, increasing and decreasing dramatically with chain length and degree of unsaturation, respectively. Thus, for any given level of glucose, insulin secretion will be influenced greatly not only by the combined concentration of all circulating (unbound) FFA, but also by the makeup of this FFA pool. Both factors will likely be important considerations in understanding the complex interplay between the nature of dietary fat and whole body insulin, glucose, and lipid dynamics.     

Morphology, development and comparative anatomical evaluation of the testicular excretory pathway in Acipenser.

In the differentiated state, the testicular excurrent duct system of the sturgeon begins as a longitudinal marginal network of the testis, extending along the entire length of the male gonad. From here, mesorchial transversal ducts travel to the ventral aspect of the pars sexualis of the opisthonephros where they merge behind the dorsal coelomic wall to form the longitudinal marginal network of the kidney. Then, the seminal pathways enter the confines of the pars sexualis of the opisthonephros and divide into a complicated, multipartite system consisting of (1) centropapillary ducts, situated in the center of a group of urinary collecting ducts, (2) lacunary basal sinuses, located on the bases of opisthonephric columns and (3) intracolumnar ducts running inside the renal columns, the latter representing typical functional units of the adult sturgeon kidney. The contacts between intracolumnar ducts and the vascular poles of corresponding renal corpuscles represent the urogenital junction in the sturgeon. The nephrons of the pars sexualis involved in sperm transport do not lose their urinary functions, but are histologically identical to those of the pars excretoria which are solely urinary. The opisthonephros of sturgeons grows continuously by the formation of new nephrons from an opisthonephric blastema located on the base of each renal column. A close topographical association between this blastema tissue and the lacunary basal sinuses of the testicular excurrent duct system guarantees that new renal corpuscles in the pars sexualis are included in the seminal passage from their beginning. From the urogenital junctions, on their way to the exterior, the spermatozoa have to travel through Bowman's capsules and tubules of the nephrons involved, then through the urinary collecting ducts, the wolffian duct and finally the sinus urogenitalis. The development of the testicular excurrent duct system begins in 8-month-old animals in the pregonadal area of the gonadal fold. Here, a primary gonoductal blastema proliferates to form a longitudinal network of anastomosing strands, situated in the dorsal mesogonadal attachment. From this primary longitudinal network, small tubules grow into the direction of the opisthonephros and into the direction of the testis. In the period from 8 to 18 months, the testicular excurent duct system reaches the adult state. In conclusion, the testicular excurrent ducts of sturgeons initially develop similar to those of Polypterus and in modern teleosts from a primary longitudinal system, beginning in the pregonadal area, localized in the mesogonadal attachment and extending caudally. Then, in a second step of development, the phylogenetically older situation, using parts of the kidney as passage, already seen in Chondrichthyes, but preserved also in higher vertebrates, is achieved in Acipenser. For this, seminal ducts grow into the opisthonephros and establish here the urogenital junctions with corresponding renal corpuscles. Furthermore, the initially longitudinally oriented ducts in the mesogonadal attachment partly lose their continuity and become integrated into the course of the transversal mesorchial ducts, represented by their portions with the widest lumina and the thickest walls.