Renin gene and angiotensin II AT1 receptor gene expression in the kidneys of normal and of two-kidney/one-clip rats

This study aimed to investigate the inter-relation between the angiotensin II (ANG II) AT₁ receptor and renin gene expression in rat kidneys. To this end, renin mRNA levels and mRNA levels for AT_1a and AT_1b were assayed by RNase protection in the kidneys of normal rats, in animals treated with the AT₁ antagonist losartan and in rats bearing 0.2-mm left renal artery clips for 2 days. In normal rats, we found a negative correlation between renin mRNA levels and AT_1a receptor mRNA levels. Losartan led to a fourfold increase in renin mRNA levels without changing AT₁ receptor mRNA levels. Unilateral renal artery clipping increased renin mRNA levels fourfold in the clipped kidney and suppressed renin mRNA levels in the contralateral kidneys. AT₁ receptor mRNA levels were not changed in the contralateral intact kidneys, but were significantly decreased by 15–25% in the clipped kidneys. Renin mRNA levels were inversely correlated to AT_1a mRNA levels in the clipped, but not in the contralateral, kidneys. Our findings suggest that the systemic activity of the renin angiotensin system has no regulatory influence on renal AT₁ receptor gene expression. Renin mRNA levels in normal and in clipped kidneys appear to be negatively determined by the level of AT_1a receptor gene expression. Thus modulation of AT_1a receptor gene expression could be a pathway for indirect modulation of renin gene expression by ANG II. This conclusion is in agreement with the observation that AT₁ receptor antagonists are powerful stimulators of the renin system.     

Divergent regulation of vascular endothelial growth factor and of erythropoietin gene expression in vivo

There is accumulating evidence from in vitro experiments that the gene expression of the vascular endothelial growth factor (VEGF) is, like that of the erythropoietin (EPO) gene, regulated by the oxygen tension and by divalent cations such as cobalt. Since the information about the regulation of VEGF gene expression in vivo is rather scarce, this study aimed to examine the influence of hypoxia and of cobalt on VEGF gene expression in different rat organs and to compare it with that on EPO gene expression. To this end male Sprague-Dawley rats were exposed to carbon monoxide (0.1% CO), hypoxia (8% O₂ ) or to cobalt chloride (12 and 60 mg/kg s.c.) for 6 h. mRNA levels for VEGF- 188, -164, and -120 amino acid isoforms in lungs, hearts, kidneys and livers were semiquantitated by RNase protection. For these organs we found a rank order of VEGF mRNA abundance of lung >> heart > kidney = liver. EPO mRNA levels were semiquantitated in kidneys and livers. Hypoxia, CO and cobalt increased EPO mRNA levels 60-fold, 140-fold and 5-fold, respectively, in the kidneys, and 11-fold, 11-fold and 3-fold, respectively, in the livers. None of these manoeuvres caused significant changes of VEGF mRNA in lung, heart or kidneys. Only in the livers did hypoxia lead to a significant (50%) increase of VEGF mRNA. These findings suggest that, in contrast to the in vitro situation, the expression of the VEGF gene in normal rat tissues is rather insensitive to hypoxia. In consequence, the in vivo regulation of the VEGF and the EPO genes appear to differ substantially, suggesting that the regulation of the VEGF and EPO genes may not follow the same essential mechanisms in vivo. Received: 31 July 1995/Received after revision: 20 November 1995/Accepted: 27 November 1995     

Differentiating moderate and severe depression using the Montgomery-Asberg depression rating scale (MADRS)

BACKGROUND: MADRS cut-off scores for moderate and severe depression were estimated in relation to the Hamilton Depression Rating Scale (HAMD(17)) and the Clinical Global Impressions Scale (CGI). METHOD: HAMD(17), MADRS, and CGI ratings from patients with major depression (DSM-IV) were analyzed (N=85). Receiver operating characteristics (ROC) curves were applied. RESULTS: Mean age was 51.4+/-14.5 years, 69% were female. Mean MADRS scores were 23.4+/-13.2, HAMD(17), MADRS, and CGI scores were highly correlated (r>0.85; P<0.0001). Best separation between moderate and severe depression according to CGI criteria was achieved with a MADRS score of 31 (sensitivity 93.5%, specificity 83.3%). LIMITATIONS: Studies to validate severity gradations including DSM-IV or ICD-10 diagnostic severity categories are recommended. CONCLUSIONS: Empirically based MADRS cut-off scores to separate moderate from severe depression on the basis of HAMD(17) and CGI severity ratings in patients with major depression were yielded.     

Dermatoglyphic peculiarities in patients with Williams-Beuren syndrome

The dermatoglyphic patterns of fingertips and palms of 115 patients with Williams-Beuren syndrome (WBS) were analysed and compared with the data from 199 control individuals from Germany. The following combination of dermatoglyphic patterns appears to be characteristic to WBS: an excess of whorls on all fingertips; high termination values of the main lines D, B, and A; frequent absence of C triradius (C°); high frequencies of ulnar loops on the hypothenar and distal loops on the 2nd, 3rd, and 4th inter digital areas, of distal axial triradii t", and of abnormal palmar creases such as simian crease and Sydney lines. The combination of fingertip and palmar patterns expressed by a “Log.Score-Index,” provides a high degree of discrimination between the WBS patients (92%) and the control group (88%). A “phantom picture” for WBS was constructed, which can be used for its diagnosis. © 1994 Wiley-Liss, Inc.     

Postpartum U.S. Women's Oral Health Knowledge,Attitudes, and Practices During Pregnancy

Maternal and Child Health Journal - The purpose of this study was to assess oral health knowledge, attitudes, and practices of women who had given birth in the United States within the past 2...     

Postmortem Stability of SARS-CoV-2 in Nasopharyngeal Mucosa

Analyses of infection chains have demonstrated that severe acute respiratory syndrome coronavirus 2 is highly transmissive. However, data on postmortem stability and infectivity are lacking. Our finding of nasopharyngeal viral RNA stability in 79 corpses showed no time-dependent decrease. Maintained infectivity is supported by virus isolation up to 35 hours postmortem.     

Impact of antiangiogenic treatment on the erectile function in patients with advanced renal cell carcinoma

We longitudinally assessed erectile function as well as the willingness to use pro-erectile treatment in a cohort on AAT for advanced RCC. Thirty-seven patients with advanced RCC completed the five-item version of the International Index of Erectile Function (IIEF-5) and other interview items before (T0) and 12 weeks into therapy (T12) with AAT. Patients were further asked if they were willing to use and pay out-of-pocket for on-demand treatment with phosphodiesterase-5-inhibitors (PDE-5i). Statistical analysis was performed using nonparametric hypothesis testing. The IIEF-5 score at T12 was significantly decreased compared with T0 (p < .001). Subjective patient satisfaction regarding their sexual lives was associated with higher IIEF-5 scores at both time points (p = .006 and p = .03, respectively). At T12, subjective sexual contentment showed a nonsignificant trend towards decline (p = .074). Patients who opted for medical treatment of ED showed significantly better IIEF-5 scores at both time points compared with the rest of the cohort (p < .001 and p = .005, respectively). In summary, AAT seems to have a negative effect on erectile function in RCC patients, however, the role of psychosocial issues warrants further elucidation. Affected patients may benefit from a proactive approach promoting medical treatment of erectile dysfunction during AAT.     

Pattern electroretinogram and visual evoked potential amplitudes are influenced by different stimulus field sizes and scotomata

The pattern electroretinogram and the visual evoked potential were recorded simultaneously with various stimulus fields and artificial scotomata of increasing sizes. In contrast to an earlier study, a smaller check size (20) and two stimulus field sizes (20° × 20° and 10° × 10°) for the scotomata were used. With a concentric decreasing stimulus field, a reduction of both the pattern electroretinogram and visual evoked potential was found. Both showed a simultaneous reduction of amplitudes, but, compared with the amplitude in the full field, the reduction was more extensive for the pattern electroretinogram at each test field size. This implies a greater contribution to the pattern electroretinogram from more eccentric retinal parts. An artificial central scotoma of increasing size in the 20° × 20° field had less influence on the pattern electroretinogram than on the visual evoked potential. The percentage amplitude loss of the visual evoked potential was more pronounced. The visual evoked potential was eventually abolished by a scotoma size from 10° × 10° upward, while the pattern electroretinogram was still registrable. When scotomata of similar size were introduced in a smaller (10° × 10°) field, percentage pattern electroretinogram and visual evoked potential amplitude losses were less separated than in a larger (20° × 20°) test field.     

Cationic-amphiphilic arpromidine-derived guanidines and a histamine trifluoromethyl-toluidide derivative may activate pertussis toxin-sensitive G-proteins by a receptor-independent mechanism

Formyl peptides activate superoxide anion (O₂ ^–) formation in human neutrophils and in HL-60 cells via pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G-proteins), and histamine (HA) mediates inhibition of O₂ ^– formation via H₂-receptors. We have studied the effects of lipophilic arpromidine-derived guanidines, which are potent, full H₂-receptor agonists in the guinea pig atrium, on O₂ ^– formation and on activation of G-proteins in HL-60 membranes and on purified G-proteins. We have also studied the effects of a HA trifluoromethyl-toluidide derivative (HTMT), a cationic-amphiphilic HA derivative which activates O₂ ^– formation in HL-60 cells through a mechanism which is independent of known HA receptor subtypes, on G-protein activation. Guanidines, at concentrations, up to 30 mol/l inhibited and, at concentrations above 30 mol/l, enhanced formyl peptide-induce O₂ ^– formation in neutrophils. In HL-60 cells, guanidines per se activated O₂ ^– formation. The stimulatory effects of guanidines on O₂ ^– formation were not inhibited by H₁- or H₂-receptor antagonists. In HL-60 membranes, guanidines and HTMT, activated high-affinity GTPase in a PTX-sensitive manner. These substances also increased GTP hydrolysis effected by transducin and G_i/G_o-proteins. Our data suggest that lipophilic guanidines and HTMT may act as receptor-independent activators of PTX-sensitive G-proteins, resulting in stimulation of O ₂ ^– formation.