Transcriptional cofactor dyxin mediates hypertrophic response in the heart during angiotensin II-induced hypertension.

Dyxin is a LIM-domain containing transcriptional regulator protein shown to play a role in a hypertrophic response in the heart. Here, the effect of adenoviral dyxin overexpression was studied on cardiac function and gene expression in the normal heart and in angiotensin II (Ang II)-induced hypertension in rats. The adenovirus-mediated intramyocardial gene transfer of dyxin (1.5x109 infectious units/animal) was performed into the left ventricle (LV) of Sprague-Dawley rats with and without the Ang II (33 µg/kg/h) infusion, administered via osmotic minipumps for 1 and 2 weeks. Echocardiography was used to assess the structural and functional changes. Dyxin expression and localization in the heart was analyzed with quantitative RT-PCR and immunohistochemistry, respectively. In the normal rat heart, the adenoviral overexpression of dyxin did not alter LV function in normal hearts as assessed by echocardiography. Dyxin was found to be localized in the cardiomyocytes as shown by the immunohistochemical staining. In Ang II-induced hypertrophy, echocardiographic data revealed a significant increase in the posterior wall diameter both in systole (21%, P<0.05) and diastole (21%, P<0.01) as well as in the diameter of the interventricular septum in systole (19%, P<0.05) in the dyxin-injected group compared with the LacZ-injected animals after two weeks of Ang II infusion. Interestingly, a significant decrease in the levels of both atrial natriuretic peptide (ANP) mRNA (55%, P<0.01) and B-type natriuretic peptide (BNP) mRNA (68%, P<0.05) was observed in the dyxin-injected group compared with the LacZ control group after one week of Ang II infusion. These results indicate that dyxin overexpression was deteriorative against pressure overload by inducing structural changes in the LV in rats. Interestingly, simultaneous adenoviral overexpression of dyxin suppressed the Ang II-induced changes of ANP and BNP genes suggesting that dyxin might have a role as a regulator of the cardiac hypertrophic gene program.

Optic disc hemorrhages. Analysis of stereophotographs and clinical data of 112 patients.

Examination of optic disc stereophotographs of 1,548 patients with glaucoma or suspected glaucoma revealed a disc hemorrhage in 112 cases. Multivariate analysis showed that disposition of hemorrhages on the disc is related to mean intraocular pressure, even lower levels of which increased probability of bleeding in inferior sectors, which showed hemorrhages more frequently than superior and horizontal sectors. Locations of hemorrhages correlated highly significantly with locations of neural rim notches. Predominance of large optic cups in eyes with normal central visual fields suggests that a genetically determined large cup may be a risk factor in addition to pathologic diurnal variation of IOP, which seemed more important than mean IOP in the development of hemorrhages. Capsular glaucoma was observed more seldom and low-tension glaucoma was observed more often than expected.

Fertility and growth of nulliparous ewes after feeding red clover silage with high phyto-oestrogen concentrations.

The study aimed to determine the effects of red clover (Trifolium pratense) silage with high phyto-oestrogen content on ewe performance during their first breeding season. Red clover silage containing formononetin, biochanin A, genistein, and daidzein was fed to 10 nulliparous ewes of the prolific Finnish Landrace breed before, during and after the breeding season, for a total of 5 months. A control group of 10 ewes was fed with grass silage. The mean numbers of foetuses per pregnancy were 2.1±0.7 and 2.2±0.8 for the red clover and control groups, respectively. The total mass of the uterus with its contents was significantly greater in ewes of the red clover group compared with those of the control group. This difference was mainly explained by the greater volume of foetal fluids. Serum progesterone concentration in the red clover group was significantly lower over the entire period analysed than in the control group. In conclusion, the fecundity of the ewes was not reduced by red clover feed with high phyto-oestrogen concentrations. The volume of foetal fluids increased that could increase the risk for vaginal prolapse before the term.

Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 during cardiac remodelling in rats.

AIM: Accumulating evidence supports the concept that proinflammatory cytokines play an essential role in the failing heart. We examined the concomitant tumour necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 expression in myocytes in vitro as well as in vivo in cardiac remodelling. METHODS: We assessed TWEAK and its receptor Fn14 expression in response to angiotensin (Ang) II, myocardial infarction (MI) as well as to local adenovirus-mediated p38 gene transfer in vivo. The effect of various hypertrophic factors and mechanical stretch was studied in neonatal rat ventricular myocyte cell culture. RESULTS: Ang II increased Fn14 levels from 6 h to 2 weeks, the greatest increase in mRNA levels being observed at 6 h (6.3-fold, P < 0.001) and protein levels at 12 h (4.9-fold, P < 0.01). TWEAK mRNA and protein levels remained almost unchanged during Ang II infusion. Likewise, a rapid and sustained elevation of Fn14 mRNA and protein levels in the left ventricle was observed after experimental MI. Moreover, local p38 gene transfer increased Fn14 mRNA and protein but not TWEAK levels. Fn14 immunoreactive cells were mainly proliferating non-myocytes in the inflammation area while TWEAK immunoreactivity localized to cardiomyocytes and endothelial cells of the coronary arteries. Hypertrophic agonists and lipopolysaccharide increased Fn14 but not TWEAK gene expression in neonatal rat myocytes, while mechanical stretch upregulated Fn14 and downregulated TWEAK gene expression. CONCLUSIONS: In conclusion, the cardiac TWEAK/Fn14 pathway is modified in response to myocardial injury, inflammation and pressure overload. Furthermore, our findings underscore the importance of Fn14 as a mediator of TWEAK/Fn14 signalling in the heart and a potential target for therapeutic interventions.

Optic disc drusen and tumours of the chiasmal region.

Two patients with optic disc drusen and tumour of the chiasmal region are presented. The association of optic disc drusen and intracranial space-occupying lesion is probably a chance occurrence. In spite of the recognition of the optic disc drusen, certain findings indicate further examinations. Progressive loss of central visual acuity unexplained by retinal pathology is an indication for a neurological investigation. Bitemporal and homonymous hemianopic visual field defects as well as evidence of papilloedema warrant a neurological evaluation.

Pseudopapilloedema with and without verified optic disc drusen. A clinical analysis II: visual fields.

An analysis of visual field findings in the material of 200 patients with pseudopapilloedema with and without verified optic disc drusen was performed. Goldmann and/or Friedmann visual fields were examined in 383 eyes. Visual field defects were found in 38.9% of the pseudopapilloedema eyes without verified drusen, but in 73.4% of the drusen eyes. The strongest field defects were found only in the eyes with drusen seen by oblique illumination or with superficial drusen. The eyes with superficial drusen showed visual field defects in 85.8%. Only 7 patients complained of visual field defects. A progression of visual field defects could be documented in 22% of 118 patients with visual field examinations 2 or more times.

Pseudopapilloedema with and without verified optic disc drusen. A clinical analysis I.

A clinical analysis of 200 patients (307 eyes with optic disc drusen, 40 eyes with pseudopapilloedema without verified drusen, 53 normal fellow-eyes) was performed to document the characteristic findings in pseudopapilloedema with and without verified drusen. In 4 eyes optic disc drusen accounted for diminished visual acuity. Papillary or peripapillary haemorrhages were found in 6.1% of 347 eyes. Peripapillary pigment epithelial derangement was present in 29.7% of the eyes, mostly with superficial drusen. Subjective symptoms caused by drusen were very rare. Changes in the appearance of the optic discs with drusen during the years could be documented in 15% of 153 patients. There were 5 patients with pigmentary retinopathy. The most usual of coincident disorders was migraine in 21 patients. The visual field findings are analysed in a companion report.

Asymmetry of retinitis pigmentosa-related to initial optic disc vasculitis.

A case of highly asymmetric retinitis pigmentosa is reported. Signs of pigmentary retinopathy appeared in the first eye following optic disc vasculitis or neuroretinitis of unknown etiology. Within 2 years the visual field became markedly restricted and the dark adaptation thresholds elevated. Twelve years later this eye was almost blind and the ERG was non-recordable. In the fellow eye, the first pigmentary changes were observed 5 years after the initial presentation, and the progression was slow. Nineteen years after the initial examination the visual field of the less affected eye was constricted to 30 degrees nasally and 60 degrees temporally, the dark adaptation threshold was only slightly elevated, and the full-field ERG was within normal range. It is possible that neuroretinitis or vasculitis of the optic disc caused the earlier onset and the more progressive course of pigmentary retinopathy in the initially affected eye.

Optic disc drusen--a photographic study. I. Autofluorescence pictures and fluorescein angiography.

As part of an examination of 180 patients with optic disc drusen, autofluorescence pictures had been taken in 116 patients and fluorescein angiograms in 67 patients. The superficial optic disc drusen often show a very bright nodular autofluorescence, but more important is the diffuse, not so intensive autofluorescence that the buried drusen may show. Thus, a diagnosis of hidden drusen can also be made if autofluorescence can be demonstrated. Fluorescein angiography may also reveal the buried drusen that do not show autofluorescence, and it may be of help in the differential diagnosis of pseudopapilloedema from true papilloedema. It may also indicate anomalous vascular patterns that may be associated with optic disc drusen.

Optic disc drusen--a photographic study. II. Retinal nerve fibre layer photography.

As part of an examination of 180 patients with optic disc drusen fundus photographs of 159 cases were evaluated. Twenty-one patients had no fundus photographs, and 12 cases had only autofluorescence pictures, positive colour transparencies or fluorescein angiograms. Peripapillary retinal nerve fibre layer (RNFL) was examined in 147 patients from black-and-white stereo-photographs of the optic disc (116) or from special RNFL pictures (4) or from both (27). Fifty-three of 147 patients had been photographed two or more times during the years from 1967 to 1981. The regional grading of the RNFL was performed separately from 6 sectors around the disc from 386 series of photographs, and the findings were later compared with the patients' visual fields. The eyes with buried drusen usually showed normal RNFL and normal fields, but the visible drusen were often associated with thinning or slits or atrophy of the peripapillary nerve fibre bundles and with visual field defects.

Electroretinography by skin electrodes and signal averaging method.

In the investigation of suspected visual disorders, ERG is of considerable value. A simplified method for clinical electroretinography by non-corneal electrodes is presented. The latency and amplitude values were measured in 22 normal subjects. Using skin electrodes and signal averaging, we can record, without discomfort to the patient, an electroretinogram with a waveform and time relations similar to those obtained by corneal electrodes. Non-corneal ERG is useful for infants, children as well as sensitive adult patients, and is also applicable after recent eye surgery and in cases of infection or injury of the anterior segment. Since non-corneal electrodes do not obstruct the stimulus light or cause of refractive change, they are advantageous when ERG is recorded simultaneously with visually evoked cortical response (VER). When it is important to stimulate only one eye at a time in flash VER, the adequacy of the cover is verified by the absence of an ERG from the covered eye.

Ophthalmic changes in hydrocephalus. A follow-up examination of 50 patients treated with shunts.

Fifty children shunted for hydrocephalus aged 5-17 years underwent a later ophthalmological examination. Corrected vision of 0.9 or less was found in 45 out of 93 eyes; in 21 patients this was the vision of both eyes. Corrected vision 0.3 or less was found in 7 eyes; in 3 patients this was the vision of both eyes. Hyperopia greater than or equal to +2.0 D was found in 20%, myopia greater than or equal to -0.5 D in 13% and astigmatism greater than or equal to 1.0 D in 25.5% of 98 eyes. Clear nystagmus was present in 18% of patients. Heterophoria was found in 20% and manifest horizontal strabismus in 33%, but no paretic squint. The optic disc was considered normal in 36 out of 100 eyes on ophthalmoscopy and in 35 out of 78 eyes on colour photography. Retinal nerve fibre layer photographs showed normal nerve fibres in 49 out of 71 eyes. The Friedmann field was in the normal range in 33 out of 53 eyes, and the Goldmann field was normal in 37 out of 44 eyes. Right homonymous hemianopia was discovered in 2 patients. The Harrington-Flocks field was normal in 17 out of 24 eyes, and 1 patient had left homonymous hemianopia. The HRR test showed a red-green disturbance in 22 out of 71 eyes. The Farnsworth panel D-15 desaturated test was entirely normal in only 4 out of 65 eyes, but the errors were only slight in 48 cases.

Neurological findings in patients with pseudopapilloedema with and without verified optic disc drusen.

As part of a clinical examination of 200 patients with pseudopapilloedema with and without verified optic disc drusen, neuroophthalmological examinations were performed in 158, neurological examinations in 117 and electroencephalography in 109 patients. Headache and suspected papilloedema were the most frequent reasons for referral. Headache was one of the complaints in 102 patients. Migraine was diagnosed in 22 and suspected in 3 patients. Epilepsy was present in 9 patients and in addition, 1 patient had had treatment for convulsions in childhood. 2 patients had a pituitary tumour and 1 had a tumour in the hypothalamic region. Various other neurological disorders appeared in small numbers. Abnormalities in electroencephalograms (EEGs) were found in 36 patients. Progressive loss of central visual acuity unexplained by retinal pathology as well as bitemporal and homonymous hemianopic visual field defects and also evidence of papilloedema warrant a neurological examination in patients with optic disc drusen.