Cerebral blood flow and cerebral metabolism in acute increase of intracranial pressure

Summary The effects of a stepwise acute increase of intracranial cerebrospinal fluid pressure on cerebral blood flow, cerebral arteriovenous differences of oxygen and glucose and on the output of lactate were studied in anaesthetized normoventilated normoxic dogs. Intracranial hypertension was produced by infusing mock-CSF into the cisterna magna. Mean arterial blood pressure was kept at a constant level throughout the experimental investigations. At a cerebral perfusion pressure of about 70 mm Hg, CBF and the cerebral metabolic rates of oxygen and glucose were not significantly changed. However, further reduction in the cerebral perfusion pressure to below 40 mm Hg, was accompanied by a statistically significant decrease of CBF and a deterioration of the oxidative metabolism. Glucose uptake was particularly disturbed by raised intracranial pressure. Increased cerebral output of lactate and low CMRO₂ indicated raised glycolysis. But (V-A)lactate was also increased at a relatively moderate reduction of the cerebral perfusion pressure, when autoregulation was still effective and CMRO₂ unchanged. The data are discussed in context with similar experimental results recently published by other investigators.Herrn Prof. Dr. H. Penzholz zum 60. Geburtstag gewidmet.     

Veränderungen von Durchblutung und oxydativem Stoffwechsel des Gehirns bei Patienten mit einer Demenz

The purpose of this retrospective study was to investigate how the blood flow and oxidative metabolism of the brain was changed in dementia and the influence of the age factor. Cerebral blood flow (CBF) was measured in 115 patients aged from 40 to 83 years by means of the Kety-Schmidt technique with the modification of Bernsmeier and Siemons. The cerebral metabolic rates of oxygen and CO2 were determined by the van Slyke method and by gaschromatography respectively and of glucose and lactate by standard enzymatic methods. All cases of dementia due to head injuries, cerebral infections, cerebral infarctions, exogenous or endogenous intoxications or circulatory diseases were excluded from this study, but no classification of the dementias was made. Statistical calculations were carried out by means of the analysis of variance for a two-way design. Cerebral blood flow did not show a normal distribution curve but was at least triphasic; CBF in demented patients was either lower than normal, normal or higher than normal. The distribution curves showed further that a low cerebral blood flow of mean 32.5 ml/100 g min coincided with a low CMR oxygen of 2.50 ml/100 g min; however, CMR glucose was either low (2.50 mg/100 g min), or nearly normal (4.50 mg/100 g min) or elevated (7.50 mg/100 g min). A normal (45.0 ml/100 g min) or enhanced (62.5 ml/100 g min) CBF correlated with a CMR oxygen which was either decreased to 2.75 ml/100 g min or increased to 4.75 ml/100 g min; CMR glucose was either decreased to 1.50 mg/100 g min, or nearly normal (4.50 mg/100 g min), or was elevated to 6.50 and 10.50 mg/100 g min with respect to the peaks of the distribution curves. It is assumed that the variability of the findings with respect to the blood flow and oxidative metabolism of the brain in dementia is due to different pathophysiological and pathobiochemical disturbances in the brain. A significant influence of age on CBF and metabolism in patients with dementia was not found.     

Fish somatostatin sst3 receptor: comparison of radioligand and GTPgammaS binding, adenylate cyclase and phospholipase C activities reveals different agonist-dependent pharmacological signatures

1 The fish somatostatin receptor 3 (fsst3) is one of the few somatostatin (SRIF) receptors cloned from a non-mammalian species so far. Here we extended our earlier characterization of this receptor by investigating the guanine nucleotide sensitivity of agonist radioligand binding at the fsst3 receptor recombinantly expressed in CCL39 (Chinese hamster lung fibroblast) cells. Further, we measured somatostatin (SRIF) and cortistatin (CST) analogues stimulated GTPgammaS binding, inhibition of forskolin-stimulated adenylate cyclase (FSAC) and stimulation of phospholipase C (PLC) activities. The present transductional data were then compared with previous radioligand binding and/or second messenger features determined for fsst3 and/or human SRIF receptors (hsst2, hsst3 and hsst5). 2 The GTP analogue guanylylimidodiphosphate (GppNHp) inhibited binding of [125I]CGP 23996 and [125I][Tyr3octreotide by 72 and 83% suggesting preferential labelling of G-protein-coupled fsst3 receptors. By contrast, [125I]LTT-SRIF28 and [125I][Tyr10]CST14 binding was rather GppNHp insensitive (42 and 35% inhibition) suggesting labelling of both coupled and non-coupled receptor states. These results might explain the apparent higher receptor densities determined in saturation experiments with [125I]LTT-SRIF28 and [125I][Tyr10]CST14 (4470 and 4030 fmol mg(-1)) compared with [125I]CGP 23996 and [125I][Tyr3]octreotide (3420 and 1520 fmol mg(-1)). 3 SRIF14 (10 microm)-stimulated specific [35S]GTPgammaS binding by three-fold; SRIF28 and octreotide displayed full agonism, whereas most other ligands displayed 60-80% intrinsic activity compared with SRIF14. SRIF14 and SRIF28 inhibited forskolin-stimulated AC (FSAC) activity by 60%; all tested ligands except BIM 23056 inhibited FSAC with comparable high intrinsic activities. SRIF14 stimulated PLC activity five- to six-fold, as determined by measuring total [3H] IP(x) accumulation; it was rather insensitive to pertussis toxin (PTX, 100 ng ml(-1), 21% inhibition), which suggests the G(q)-family proteins couple to PLC activity. SRIF14, SRIF28 and [Tyr10]CST14 showed full agonism at PLC, whereas all other ligands behaved as partial agonists (20-70% intrinsic activity). BIM 23056, which showed weak partial or no agonism, antagonized SRIF14-induced total [3H]-IP(x) production (pK(B) = 6.83), but failed to block competitively agonist-stimulated [35S]GTPgammaS binding or agonist-induced inhibition of FSAC activity. 4 Comparison of the pharmacological profiles of fsst3 receptors established in GTPgammaS binding, FSAC inhibition and PLC stimulation resulted in low correlations (r = 0.410-0.594). Both rank orders of potency and rank orders of relative efficacy varied in the three second messenger experiments. Significant, although variable correlations were obtained comparing GTPgammaS binding and inhibition of FSAC activity with previously reported affinity profiles of [125I]LTT-SRIF28, [125I][Tyr10]CST14, [125I]CGP 23996, [125I][Tyr3]octreotide (r = 0.75-0.83; 0.68-0.89). By contrast, the PLC stimulation and radioligand-binding profiles did not correlate. 5 Comparison of the functional data (GTPgammaS binding, FSAC inhibition, PLC stimulation) of fsst3 receptors with those of human sst2, sst3, sst5 receptors expressed in CCL39 cells resulted in highest correlation with the hsst5 receptor (r = 0.94, 0.97, 0.49) > hsst2 (0.80, 0.50, n.d.) > hsst3 (0.25, 0.19, 0.17). 6 In summary, fsst3 receptors expressed in CCL39 cells are involved in signalling cascades similar to those reported for mammalian SRIF receptors, suggesting SRIF receptors to be highly conserved in evolution. Binding and functional data showed highest similarity of fsst3 receptors with the human sst5 receptor subtype. Different affinities, receptor densities and GppNHp-sensitivities determined with the four radioligands (agonists) are assumed to results from ligand-specific states of the fsst3-ligand complex. The differences in the rank orders of potency and relative efficacy in the various signalling cascades may be explained by agonist-induced receptor trafficking.     

Marketing mental health to men: theoretical and practical considerations

The current paper addresses the importance of and relevant challenges pertaining to the marketing of mental health to men. Included are pertinent definitions, a review of related research, and a discussion of recent large-scale gender-specific mental health campaigns. In addition, central aspects of the social marketing framework considered to be particularly useful for addressing men's resistance to help seeking are reviewed. Suggestions for future research topics are also provided.     

Pathophysiology of Tamm-Horsfall protein.

Tamm-Horsfall protein, a renal glycoprotein present in normal urine, is the primary constituent of urinary casts. Immunoelectron microscopy has shown that this protein is localized selectively along surface membranes of the thick ascending loop of Henle. In this surface membrane site, the unique aggregation and gel formation of Tamm-Horsfall protein in response to increasing concentrations of electrolytes within physiologic ranges may influence the permeability characteristics of this nephron segment. These aggregation characteristics also play a role in pathologic conditions and lead to the prolonged persistence of interstitial Tamm-Horsfall protein deposits in several tubulointerstitial diseases. Recent studies have demonstrated immunologic responses to this protein, including an immune complex tubulointerstitial nephritis in rats mediated by autoantibodies to Tamm-Horsfall protein.     

Uptake of polyvinyl alcohol by macrophages in the glomerular mesangium of rats. Histologic and functional studies

Rats received daily subcutaneous injections of the synthetic polysaccharide polyvinyl alcohol (PVA) for 1-28 days. The amount of PVA localized in the glomerular mesangium increased progressively during this time. By 28 days, all glomeruli showed extensive intracellular mesangial sequestrations of PVA, causing marked widening of mesangial areas, while the peripheral capillary loops were unaltered. Overall glomerular hypercellularity was mild to moderate, occurring mainly in areas of PVA deposition. Follow-up studies after 6, 12, 26, and 40 weeks revealed partial reduction of glomerular PVA masses. The PVA deposits were frequently associated with nonspecific esterase (NSE)-positive cells. The number of NSE-positive cells per glomerular tuft section increased from 0.1 in controls, to 2.1, 4.0, and 4.5 after 3, 14, and 28 days of PVA treatment, respectively. Similarly, glomerular counts for Ia-antigen-bearing cells rose from 2.1 in controls to 4.8 on Day 3 and showed further increases at later time periods with confluent staining of clusters of Ia-positive cells. In glomeruli, Ia-bearing cells were mainly noted in PVA-positive mesangial areas. These results indicate that PVA is taken up in the glomerulus primarily by cells that are NSE- and Ia-antigen-positive, suggesting that these cells are activated blood-borne monocyte-macrophages that sequester this polysaccharide. Clearance studies revealed that the glomerular filtration rate and effective renal plasma flow remained normal after 4 weeks of PVA injections. PVA-treated rats showed only mild elevations of urinary protein excretion. These findings indicate that confinement of marked structural and cellular alterations to the mesangium, even including the presence of infiltrating monocyte-macrophages, is compatible with absent or minimal dysfunction of the glomerular ultrafilter.     

Zur Chemie des 6-Azabicyclo [3.2.1] octans Stickstoffhaltige Bicyclen III

6-Azabicyclo [3,2,1] octanes The synthesis of the secondary and tertiary 6-azabicyclo [3,2,1] octanes 4 and 6 via the corresponding lactam 3 and 5 is described. The stereochemistry is discussed and the course of the Hofmann-degradation of 6b clucidated.     

The high-riding superior aortic recess of the pericardium: MRI visualization in a child

We report a 4-year-old child with a high-riding superior aortic recess of the pericardium, initially misdiagnosed as a possible vascular malformation. The anatomy of the pericardial recesses is reviewed.