PET imaging of the dopamine transporter with 18F-FECNT: a polar radiometabolite confounds brain radioligand measurements.

18F-2beta-Carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (18F-FECNT), a PET radioligand for the dopamine transporter (DAT), generates a radiometabolite that enters the rat brain. The aims of this study were to characterize this radiometabolite and to determine whether a similar phenomenon occurs in human and nonhuman primate brains by examining the stability of the apparent distribution volume in DAT-rich (striatum) and DAT-poor (cerebellum) regions of the brain. METHODS: Two rats were infused with 18F-FECNT and sacrificed at 60 min. Extracts of brain and plasma were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometric (LC-MS) techniques. Two human participants and 3 rhesus monkeys were injected with 18F-FECNT and scanned kinetically, with serial arterial blood analysis. RESULTS: At 60 min after the injection of rats, 18F-FECNT accumulated to levels about 7 times higher in the striatum than in the cortex and cerebellum. The radiometabolite was distributed at equal concentrations in all brain regions. The LC-MS techniques identified N-dealkylated FECNT as a major metabolite in the rat brain, and reverse-phase HPLC detected an equivalent amount of radiometabolite eluting with the void volume. The radiometabolite likely was 18F-fluoroacetaldehyde, the product expected from the N-dealkylation of 18F-FECNT, or its oxidation product, 18F-fluoroacetic acid. The distribution volume in the cerebellum increased up to 1.7-fold in humans between 60 and 300 min after injection and 2.0 +/- 0.1-fold (mean +/- SD; n = 3) in nonhuman primates between 60 and 240 min after injection. CONCLUSION: An 18F-fluoroalkyl metabolite of 18F-FECNT originating in the periphery confounded the measurements of DAT in the rat brain with a reference tissue model. Its uniform distribution across brain regions suggests that it has negligible affinity for DAT (i.e., it is an inactive radiometabolite). Consistent with the rodent data, the apparent distribution volume in the cerebellum of both humans and nonhuman primates showed a continual increase at late times after injection, a result that may be attributed to entry of the radiometabolite into the brain. Thus, reference tissue modeling of 18F-FECNT will be prone to more errors than analysis with a measured arterial input function.     

Xanthogranulomatous orchitis: Review of the published work and report of one case

Xanthogranulomatous orchitis is an extremely rare inflammatory non-neoplastic destructive lesion of the testis. We report a 44-year-old man who presented with right scrotal swelling and two discharging sinuses. Testicular tumor markers were normal. Scrotal ultrasound showed heterogeneous testicular areas and irregular margin of the tunica. Surgical exploration revealed infected, unhealthy testicular tissue with necrosis and tumor-like lesion. Orchidectomy was done and histopathology showed xanthogranulomatous orchitis.     

Haemorrhagic pituitary tumours

In a group of 69 patients with pituitary tumours, 12 were found to have evidence of intratumoral haemorrhage on MRI, characterized by high signal intensity on short TR/TE sequences. This was verified in all but 1 patient. The majority of the bleedings occurred in macroadenomas. Five (42%) were prolactinomas and 4 (33%) were non-functioning adenomas. There were 2 GH- and 1 ACTH-secreting tumours. All 5 patients with prolactinomas were on bromocriptine medication. Two of the patients had a clinical picture of pituitary apoplexy. The haemorrhage was not large enough to prompt surgery in any of the patients. However, surgical verification of the diagnosis was obtained in 5 cases, while 6 patients were examined with follow-up MRI.     

Innate immunity and its role against infections.

LEARNING OBJECTIVES: This article reviews current concepts of the innate immune system that offers protection against infections. It offers an overview for the readers to understand how innate immunity, consisting of different receptors, cells, and mediators recognizes pathogens and exerts protective function against pathogens. DATA SOURCES AND STUDY SELECTION: MEDLINE-search articles including original research papers, review articles, textbooks, and references identified from bibliographies of relevant articles. RESULTS AND CONCLUSIONS: The innate immune system is nonspecific immunity present since birth not requiring repeated exposure to pathogens. It is capable of differentiation between self and nonself. Because of its nonspecificity, it has a broad spectrum of resistance to infection. Further, it is thought to play an important role in the control of adaptive immunity by regulating co-stimulatory molecules and effector cytokines. Innate immunity includes pattern recognition molecules/receptors, antimicrobial peptides, the complement system, inflammatory mediators, and cytokines produced by immune cells. Pattern recognition molecules/receptors recognize pathogen-associated molecular patterns that are essential for microorganisms' survival and pathogenicity. Although innate immunity has recently gained increasing importance, further studies are necessary for a better understanding of its role.     

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.