Clinical pharmacology of the new COMT inhibitor CGP 28 014

CGP 28 014 is a specific inhibitor of catechol-O-methyltransferase (COMT) in vivo. In humans, the inhibition was assessed by measuring urinary excretion of isoquinolines and with the levodopa test. Following administration of CGP 28 014, urinary excretion of isoquinolines was significantly increased. In rats, CGP 28 014 reduced plasma and striatal concentrations of 3-O-methyldopa (30MD) in a dose-dependent manner. Acute and subchronic administration of CGP 28 014 alone or in combination with the peripherally acting decarboxylase inhibitor benserazide decreased plasma 30MD as an index of COMT inhibition by about 50%. There seems to be a close relationship between the time-course of plasma concentrations of CGP 28 014 and the extent of COMT inhibition assessed by the 30MD/DOPA ratio in plasma.     

Human appropriation of net primary production as driver of change in landscape-scale vertebrate richness

Aim

Land use is the most pervasive driver of biodiversity loss. Predicting its impact on species richness (SR) is often based on indicators of habitat loss. However, the degradation of habitats, especially through land-use intensification, also affects species. Here, we evaluate whether an integrative metric of land-use intensity, the human appropriation of net primary production, is correlated with the decline of SR in used landscapes across the globe.

Location

Global.

Time period

Present.

Major taxa studied

Birds, mammals and amphibians.

Methods

Based on species range maps (spatial resolution: 20 km × 20 km) and an area-of-habitat approach, we calibrated a “species–energy model” by correlating the SR of three groups of vertebrates with net primary production and biogeographical covariables in “wilderness” areas (i.e., those where available energy is assumed to be still at pristine levels). We used this model to project the difference between pristine SR and the SR corresponding to the energy remaining in used landscapes (i.e., SR loss expected owing to human energy extraction outside wilderness areas). We validated the projected species loss by comparison with the realized and impending loss reconstructed from habitat conversion and documented by national Red Lists.

Results

Species–energy models largely explained landscape-scale variation of mapped SR in wilderness areas (adjusted R²-values: 0.79–0.93). Model-based projections of SR loss were lower, on average, than reconstructed and documented ones, but the spatial patterns were correlated significantly, with stronger correlation in mammals (Pearson's r = 0.68) than in amphibians (r = 0.60) and birds (r = 0.57).

Main conclusions

Our results suggest that the human appropriation of net primary production is a useful indicator of heterotrophic species loss in used landscapes, hence we recommend its inclusion in models based on species–area relationships to improve predictions of land-use-driven biodiversity loss.     

Vascular morphology of the bovine spermatic cord and testis

Summary The highly coiled testicular artery within the bovine spermatic cord has a constant luminal diameter but a continuously decreasing mural thickness. The pampini form plexus is composed of three interconnected venous networks differing in mesh sizes and calibres. The large veins of the first network display pouches and permanent constrictions, which may serve as throttle devices. The constitutents of the third network are venules or venous capillaries with diameters between 10 and 20 m; they favor a periarterial position or even occupy the media-adventitia border of the testicular artery. All plexus veins are devoid of valves. The existence of true arteriovenous anastomoses between smaller branches of the testicular artery and plexus veins was established by serial sections. The vascular morphology of the spermatic cord is discussed with special attention to a postulated venous-arterial steroid transfer in this region.Supported by the Deutsche Forschungsgemeinschaft and the Stiftung zur Förderung der wissenschaftlichen Forschung an der Universität Bern     

Intertubular topography in the bovine testis

Summary The intertubular stroma of the bovine testis is composed of narrow strands between two adjacent tubules and larger tri- and quadrangular interstices between three to four tubules. The latter contain the majority of Leydig cells, larger blood vessels and testicular lymph vessels. Ley dig cells occur in groups or cords, not every cell being in close contact to a capillary, lymph vessel or venule. Between adjacent Leydig cells intercellular canaliculi and gap junctions are frequently encountered. Bovine Leydig cells are further characterized by an abundance of ribosome-associated endoplasmic reticulum, by mitochondria often containing crystalloid structures and displaying both tubular and lamelliform cristae, as well as by a relative paucity of lipid droplets and lysosomes. Independent of the size of intertubular lymph vessels their walls consist only of an endothelium of varying thickness, no typical basal lamina or associated musculature being present. The interstitial surface of the endothelium sends anchoring cytoplasmic pedicles into the subjacent ground substance and collagen fibrils. Among occasional plasma cells, mast cells and mononuclear leucocytes, a regular constituent of the intertubular region studied is a population of electron-lucid, irregularly shaped cells (light intercalated cells = LIC) with slender, pleomorphic processes. These cells are believed to be involved in testicular androgen storage and distribution.Supported by a grant from the Deutsche Forschungsgemeinschaft     

Development of the bovine acrosome

Summary In the present study the development of the bovine acrosome was investigated using conventional electron-microscopical techniques as well as the phosphotungstic-acid (PTA) technique (Rambourg 1967) including enzymatic digestion experiments. As in other species and in accordance with previous light-microscopical studies (Clermont and Leblond 1955) four phases of acrosomal differentiation can be discerned: the Golgi-phase, cap-phase, acrosome-phase, and maturation-phase.In the bull no internal pattern of the acrosomal content can be observed, either with conventional uranyl acetate-lead citrate staining or with the PTA-techniques. Our results support the observation in other species (Fawcett et al. 1971) that no intrinsic polymerization or crystallization process of the acrosomal content is responsible for acrosomal shaping. Some of our results suggest the influence of external forces on acrosomal development in the bull. During the cap-phase and the acrosome-phase accumulations of smooth endoplasmic reticulum and a layer of fine filaments can be observed in the Sertoli-cell cytoplasm, immediately adjacent to the developing acrosome. A temporary influence of these structures on acrosomal development seems possible. The PTA-positive staining of the developing bovine acrosome is probably due to the presence of acrosomal glycoproteins; however, our results do not exclude the possibility that molecules other than glycoproteins contribute to the positive PTA-staining of the developing acrosome.Supported by a grant from the Deutsche Forschungsgemeinschaft     

Terpen-derivate aus Senecio-arten

Investigation of about 50 Senecio species has afforded many new substances, in addition to known compounds. Present in these plants are 23 fura     

Weitere furanoeremophilane aus Othonna-arten

The investigation of further Othonna species affords 23 new furanoeremophilanes and a new benzofuran-derivative. All these compounds are closely related to those isolated before from other Othonna species. Highly oxidized furanoeremophilanes seem to be typical of this genus.     

Strukturanalyse der methyl-2,3,6-tridesoxy-2-C-[2-hydroxy-1,1-(Äthylendithio)Äthyl]-α-l-threo-hexopyranosid-4-ulo-22,4-pyranose

Methyl 2,3,6-trideoxy-2-C-[2-hydroxy-1,1-(ethylenedithio)ethyl]-α-l-threo-hexopyranosid-4-ulo-2²,4-pyranose (1) crystallizes in a rhombic space group P2₁2₁2₁ with four molecules in the elementary unit. The structure was refined to an R-value of 0.057. The aldopyranose ring adopts a ¹C₄ conformation with an axial side-chain forming a hemiacetal ring to the keto group at C-4. Both six-membered rings connected in the 2,7-dioxabicyclo[3.3.1]nonane system differ only slightly from the ¹C₄ chair conformation. The spirocyclic dithiolane ring adopts a nearly ideal envelope form with a deviation of C-21 from the plane S-1-C-7-S-2-C-22. The dihedral angle O-5-C-1 O-1-C-11 of 59.1° is an agreement with the exo-anomeric effect.