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The regulation of renal function by extracellular nucleotides encompasses alterations in glomerular hemodynamics, microvascular function, tubuloglomerular feedback, tubular transport, cell growth or apoptosis, and transport of water and solutes in the medullary collecting duct. Nearly all cells can release ATP or other nucleotides that are then rapidly hydrolyzed in the extracellular milieu. However, little information is available on the cellular expression of ectoenzymes that hydrolyze extracellular nucleotides within the kidney. Nucleoside triphosphate diphosphohydrolases (NTPDases) are plasma membrane-bound ectonucleotidases. NTPDase1 has identity with CD39, a B lymphocyte activation marker, and hydrolyzes extracellular ATP and ADP to AMP within the vasculature, whereas NTPDase2/CD39L(ike)1 preferentially converts ATP to ADP outside of blood vessels. Using immunohistochemical and in situ hybridization approaches, we localized the protein and mRNA of NTPDase1 and 2 in murine renal tissues. In the renal cortex, NTPDase1 is expressed by vascular smooth muscle cells and endothelium in interlobular arteries, afferent glomerular arterioles, and peritubular capillaries. In the inner medulla, NTPDase1 is expressed in ascending thin limbs of Henle's loop, ducts of Bellini, and in the pelvic wall. In contrast, NTPDase2 is expressed in Bowman's capsule, glomerular arterioles, adventitia of blood vessels, and pelvic wall. Thus the distribution patterns of NTPDases have parallels to the known distribution of P2 receptors within the kidney. NTPDases may modulate regulatory effects of ATP and degradation products within the vasculature and other sites and thereby potentially influence physiological as well as multiple pathological events in the kidney.

The 3-methyl-4-(tricyclo[5.2.1.02,6]dec-4-en-8-ylidene)butan-2-ols (=Fleursandol®; rac-10), a new class of sandalwood odorants, were synthesized in their enantiomerically pure forms by use of tricyclo[5.2.1.02,6]dec-4-en-8-ones 17 and ent-17 and (tetrahydro-2H-pyran-2-yl)-protected 4-bromo-3-methylbutan-2-ols 22 and ent-22 as starting materials (Schemes 4;2–4). Only four of 16 possible stereoisomers of rac-10 possess the typical, very pleasant, long-lasting sandalwood odor (Table 4;1). The (2S,3R,4E,1′R,2′R,6′R,7′R)-isomer ent-10a is by far the most important representative, with an odor threshold of 5 4;μg/l in H2O.

Background:The therapy of nephrotic syndrome in focal segmental glomerulosclerosis (FSGS) is still a matter of controversy. Methods:We performed a prospective randomized study of the treatment of nephrotic syndrome due to FSGS. We compared 2 specific treatment protocols to assess the effect of treatment on proteinuria and renal function. Fifty-seven patients were randomly assigned to 2 groups: group 1 (n = 34) received steroids and cyclosporine, and group 2 (n = 23) received steroids and chlorambucil for 6 months. When treatment was refractory to chlorambucil, the patients in this group were treated with cyclosporine. Creatinine, blood urea nitrogen, proteinuria, lipids, and arterial hypertension were monitored at regular intervals. Results:Patients showed a mean serum creatinine of 1.5 ± 0.2 mg/dL (132.6 ± 17.7 μmol/L) and proteinuria of 4.8 ± 2.8 g/24 h with no differences between the groups. At the end of the chlorambucil therapy, patients in group 2 had creatinine levels of 1.8 ± 0.6 mg/dL (159.1 ± 53 μmol/L) and proteinuria levels of 3.4 ± 1 g/24 h. All patients in this group were given cyclosporine. After 4 years the mean creatinine level in group 1 was 1.7 ± 0.4 mg/dL (150.3 ± 35.4 μmol/L) and the proteinuria level was 2.5 ± 1 g/24 h. In group 2, the mean creatinine level was 1.9 ± 0.6 mg/dL (168 ± 53 μmol/L) (not significant [NS]) and the mean proteinuria level was 2.3 ± 1.1 g/24 h (NS). Full remission occurred in 23% of the patients in group 1 (n = 8) and 17% of the patients in group 2 (n = 4; NS). Partial remission was observed in 38% of the patients in group 1 (n = 13) and 48% in group 2 (n = 11; NS). The number of patients who developed end-stage renal disease was comparable in both groups: 4 of 34 patients in group 1 after 2.5 ± 0.8 years, and 5 of 23 patients in group 2 (NS). Conclusion:Additional treatment with chlorambucil was found to be ineffective in FSGS. Patients responded to treatment with steroids or cyclosporine, but additional treatment with chlorambucil did not improve the patient's outcome. Future studies must focus on the long-term prognosis of these patients.

Nucleoside triphosphate diphosphohydrolases (NTPDases) are a recently described family of ectonucleotidases that differentially hydrolyze the γ and β phosphate residues of extracellular nucleotides. Expression of this enzymatic activity has the potential to influence nucleotide P2 receptor signaling within the vasculature. We and others have documented that NTPDase1 (CD39, 78 kd) hydrolyzes both triphosphonucleosides and diphosphonucleosides and thereby terminates platelet aggregation responses to adenosine diphosphate (ADP). In contrast, we now show that NTPDase2 (CD39L1, 75 kd), a preferential nucleoside triphosphatase, activates platelet aggregation by converting adenosine triphosphate (ATP) to ADP, the specific agonist of P2Y1 and P2Y12 receptors. We developed specific antibodies to murine NTPDase1 and NTPDase2 and observed that both enzymes are present in the cardiac vasculature; NTPDase1 is expressed by endothelium, endocardium, and to a lesser extent by vascular smooth muscle, while NTPDase2 is associated with the adventitia of muscularized vessels, microvascular pericytes, and other cell populations in the subendocardial space. Moreover, NTPDase2 represents a novel marker for microvascular pericytes. Differential expression of NTPDases in the vasculature suggests spatial regulation of nucleotide-mediated signaling. In this context, NTPDase1 should abrogate platelet aggregation and recruitment in intact vessels by the conversion of ADP to adenosine monophosphate, while NTPDase2 expression would promote platelet microthrombus formation at sites of extravasation following vessel injury. Our data suggest that specific NTPDases, in tandem with ecto-5′-nucleotidase, not only terminate P2 receptor activation and trigger adenosine receptors but may also allow preferential activation of specific subsets of P2 receptors sensitive to ADP (eg, P2Y1, P2Y3, P2Y12) and uridine diphosphate (P2Y6).

The cytoarchitectural organization of the electromotor system of the electric catfish (Malapterurus electricus) was investigated in order to obtain insight into the neuronal reorganization accompanying the functional transition of a presumptive previous motor system to an electromotor system eliciting electric organ discharge. The electric catfish possesses two giant electromotoneurons situated within the rostral spinal cord. Intracellular dye injections have revealed the enormous extension of the dendritic tree of electromotoneurons. About 50 primary dendrites span the entire lateral funicle and intermediate grey matter, and reveal an extensive contralateral projection. The giant dendritic tree (1.2 mm in rostrocaudal direction) presumably receives inputs from all ascending and descending pathways of the spinal cord. Electromotoneurons and motoneurons receive the same type of fibre inputs, and electromotoneurons and interneurons are connected through common presynaptic elements. The innervation pattern of the electromotoneurons and spinal motoneurons is similar. Synaptic terminals with round synaptic vesicles often reveal chemical contacts and gap junctions. Furthermore, dendrites of the two electromotoneurons form juxtapositions (ephapses) with each other and also with spinal interneurons. Our results suggest that the two electromotoneurons are homologous to median (primary) spinal motoneurons and are the central structures of the electromotor system within the central nervous system of the electric catfish. A high capability of information processing can be attributed to the giant dendritic trees from functional considerations. This presumably enables the electromotoneurons to elicit an electric organ discharge in different behavioural contexts with a minimum of functional reorganization.

Five Jasminum grandiflorumflower absolutes harvested as flower buds and processed in the “J. sambac-way” in different locations in the southern Indian state of Tamil Nadu were analyzed using gas chromatography (GC) and GC-mass spectrometry. These absolutes were compared with 5 commercial Indian J. grandiflorumflower absolutes manufactured in the traditional “J. grandiflorum-way” from open flowers. Focus was placed on 42 key ingredients to investigate the influence of such a flower processing on the absolute composition. Our study established olfactive and composition differences of such absolutes produced via the “J. sambac-way.” In addition, geographic variations in this species were analyzed by comparing 5 commercial Indian J. grandiflorumflower absolutes with absolutes from Egypt and Morocco, respectively. A composition range of the absolutes was established for the 3 main J. grandiflorumflower grower countries using a total of 14 commercial samples. The 12 main ingredients in the absolutes showed variations between 4.3% and 89.7%.

Two Chinese black cardamom oils (Amomum tsao-ko) were analyzed using GC and GC/MS and compared to 2 Indian cardamom oils from the species Amomum subulatumand Elettaria cardamomum, respectively. The main constituents of A. tsao-kooils were eucalyptol, geranial, geraniol, trans-2,3,3A,7A-tetrahydro-1H-indene-4-carbaldehyde, (2E)-decenal, neral, and 4-indanecarbaldehyde. Special attention was given to the 1H-indene-carbaldehyes, which are frequently wrongly assigned in previous literature. A detailed odor evaluation of the oils was also carried out. In addition, composition variations of 28 main constituents of 8 E. cardamomumoils were investigated, taking various factors like origin, production methods, plant material, and drying stage into consideration.