Marked locomotor stimulation in monoamine-depleted mice following treatment with atropine in combination with clonidine

Summary The present study demonstrates that the muscarinic antagonist atropine and the -adrenergic agonist clonidine, though ineffective when administered separately, produced a pronounced locomotor stimulation in monoamine-depleted mice when combined. The atropine + clonidine-induced locomotor stimulation was counteracted by both the ₂-adrenoceptor antagonist idazoxan and the acetylcholinesterase inhibitor physostigmine. Thus, it is clear that simultaneous manipulations with cholinergic and adrenergic systems are as effective in restoring locomotion in monoamine-depleted mice as increasing central dopaminergic tone. This finding may have implications for the treatment of a movement disorder like Parkinson's disease.     

The retinal nerve fiber layer in normal and glaucomatous eyes. II. Correlations

The retinal nerve fiber layer is different in normal and glaucomatous eyes. We correlated semi-quantitative data of the retinal nerve fiber layer of 398 eyes with chronic primary open-angle glaucoma and of 234 normal eyes with the intra- and parapapillary morphometric signs and with the perimetric indices. The three parameters "sequence of the fundus sectors concerning the best visibility of the retinal nerve fiber bundles", "visibility of the nerve fiber bundles", and "localized defects" were significantly (p less than 0.001) correlated to 1) area of the neuroretinal rim as a whole and in four different optic disc sectors, 2) neuroretinal rim width determined every 30 degrees, 3) optic cup area, diameters and form, 4) horizontal and vertical cup/disc ratios and the quotient of the horizontal to vertical cup/disc ratio, 5) area and width of zone "Alpha", zone "Beta", and the total parapapillary chorio-retinal atrophy, 6) diameter of the retinal vessels, 7) grade of a "tesselated fundus", and 8) the visual field loss. If only the inferior temporal and the superior temporal sectors were considered, the retinal nerve fiber bundles were less visible in that sector with the largest notch in the neuroretinal rim, the smaller neuroretinal rim area and width, the thinner retinal vessels, and the larger zone "Alpha", zone "Beta", and total parapapillary chorio-retinal atrophy. The glaucomatous changes in the retinal nerve fiber layer are correlated in time and location with the intra- and parapapillary and the perimetric alterations. Evaluation of the retinal nerve fiber layer is a useful method to detect a glaucomatous optic nerve damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction.

Connective tissue growth factor (CTGF) is reported to be a target gene of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) in vitro. Its physiological role in angiogenesis and skeletogenesis during mouse development has been described recently. Here, we have mapped expression of CTGF mRNA during mouse heart development, postnatal adult life, and after experimental myocardial infarction. Furthermore, we investigated the relationship between CTGF and the BMP/TGFbeta signaling pathway in particular during heart development in mutant mice. Postnatally, CTGF expression in the heart became restricted to the atrium. Strikingly, 1 week after myocardial infarction, when myocytes have disappeared from the infarct zone, CTGF and TGFbeta expression as well as activated forms of TGFbeta but not BMP, Smad effector proteins are colocalized exclusively in the fibroblasts of the scar tissue, suggesting possible cooperation between CTGF and TGFbeta during the pathological fibrotic response.     

Differential responses in post- and pre-ganglionic adrenal sympathetic nerve activity and renal sympathetic nerve activity after injection of 2-deoxy-D-glucose and insulin in rats.

The aim of the study was to compare pre-ganglionic adrenal nerve activity (pre-aSNA) to post-ganglionic adrenal nerve activity (post-aSNA) in rats after administration of 2-deoxy-D-glucose (2-DG, 500 mg kg-1, i.v.), which mimicks a central hypoglycaemia or to the response in pre-aSNA and post-aSNA to hypoglycaemia after injection of insulin (5U). Renal postganglionic sympathetic nerve recordings (rSNA) in a separate group was used as a reference. Adrenal or renal multifibre nerve activity was recorded in chloralose-anaesthetized Wistar-rats. Trimethaphan, a short-lasting ganglionic blocker, was administered i.v. (10 mg kg-1) in order to test for pre- or post-aSNA in the adrenal nerves. The adrenal nerves was considered to contain predominantly post or preganglionic fibres, respectively if the nerve activity in the adrenal nerve decreased (post-aSNA) or increased (pre-aSNA). In contrast, all renal nerves showed almost a pure postganglionic activity. Post-aSNA responded with a tendency to increase after the 2-DG injection. The highest value (percentage change from control) 5 min after injection was 12 +/- 9%. The pre-aSNA increased with values of 99 +/- 52% at 3 min and 86 +/- 31% at 5 min (percentage change from control). The activity in the rSNA was only slightly decreased after the injection of 2-DG when compared to pre-drug control activity. There was a significant difference between the pre-aSNA vs. post-aSNA at 1 min (P less than 0.05), 3 min (P less than 0.01) and 5 min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

A controlled family history study of bulimia

Using the family history method, we assessed the morbid risk for psychiatric disorders in the first-degree relatives of 69 probands with bulimia, 24 probands with major depression, and 28 nonpsychiatric control probands. The morbid risk for major affective disorder among the first-degree relatives of the bulimic probands was 32%, significantly greater than that found in the nonpsychiatric control probands. The rate of familial major affective disorder was significantly greater in bulimic probands who had a history of major affective disorder themselves than in bulimic probands without such a history - but the latter group, in turn, displayed significantly higher rates than the nonpsychiatric control probands. Eating disorders were slightly, but not significantly, more prevalent in the families of bulimic probands than nonpsychiatric control probands. We present two alternative hypotheses which might explain these findings.     

Improvement in histological diagnosis of primary hyperparathyroidism with a monoclonal antiparathyroid antibody

The monoclonal antiparathyroid antibody E11 reacts with a glycoprotein of high molecular weight, which acts as a calcium receptor on the surface of parathyroid cells and mediates calcium regulation of parathyroid hormone (PTH) release. Reduced expression of the calcium receptor has been implicated as a cause of the defect in PTH regulation in the pathological parathyroid parenchyma of patients with hyperparathyroidism (HPT). The present study evaluated the efficacy of immunostainings with the E11 antibody in comparison with routine histopathological methods including staining by the oil red O technique for histological discrimination between normal and pathological parathyroid glands. Parathyroid tissue from euparathyroid individuals invariably presented intense and homogeneous surface staining, with the antibody on virtually all chief cells, while the pathological glands from patients with HPT consistently showed heterogeneous and reduced immunostaining. Even minimally enlarged pathological glands from individuals with mild hypercalcemia and the normal-sized glands associated with adenomas displayed parathyroid chief cells with reduced antibody reactivity. The monoclonal antiparathyroid antibody should constitute a useful tool in parathyroid histopathology not only by its ability to identify the parathyroid tissue, but also by directly demonstrating the functionally normal and abnormal cells within the parathyroid tissue.     

Anti-actin specificity of human smooth muscle antibodies in chronic active hepatitis.

Thirty sera reacting by IFL technique in titres greater than or equal to 100 with smooth muscle fibres of rat stomach, rat renal glomeruli, and with the membrane region of thyroid cells were randomly chosen among sera sent in for routine testing of tissue antibodies. All sera but one were found to be derived from patients with chronic active hepatitis. The smooth muscle and other relevant cell staining were abolished after absorption of sera with actin, prepared from rabbit skeletal muscle and found to be homogeneous by SDS gel-electrophoresis and by electron microscopy. The actin anti-bodies were purified by precipitation of sera with F-actin and elution of the precipitates at acid pH. The purified antibodies stained all tissues in the same way as the original sera. In double immunodiffusion tests all thirty sera gave precipitation with actin. Thus, it was concluded that these broad-reacting SMA are directed against actin. The finding of high-titred SMA is of diagnostic value and supports the clinical diagnosis of active chronic hepatitis. In addition, anti-actin antibodies eluted from human sera are a suitable tool for studying actin-containing cellular structures.     

Potentiation by sulfide of hydrogen peroxide-induced killing of Escherichia coli.

L-Cysteine potentiates 100-fold the hydrogen peroxide-induced killing of a growing culture of Escherichia coli K-12 (Berglin et al., J. Bacteriol. 152:81-88). In the present study it is shown that hydrogen sulfide is formed from L-cysteine and that sodium sulfide could substitute for L-cysteine in the potentiation of hydrogen peroxide-induced killing of E. coli K-12. Addition of an amino acid, L-leucine, L-valine, or L-alanine, to an L-cysteine-containing medium with a growing culture of E. coli K-12 inhibited hydrogen sulfide formation and the potentiation of hydrogen peroxide-induced killing. These amino acids did not inhibit hydrogen sulfide formation from L-cysteine by a cell extract, and they did not inhibit the potentiation by sulfide of hydrogen peroxide-induced killing. This indicated that the amino acids protected the culture from L-cysteine-potentiated, hydrogen peroxide-induced killing by inhibiting the transport of L-cysteine into the cell. The potentiation by sodium sulfide of hydrogen peroxide-induced killing was abolished by the metal ion chelator 2,2'-bipyridyl. This indicated that metal ions, in addition to sulfide, were involved in the killing. Toxic effects of hydrogen peroxide are often presumed to be mediated by hydroxyl radicals formed in iron-catalyzed reactions. It was demonstrated that iron sulfide was more efficient than ferrous iron in catalyzing the formation of hydroxyl radicals from hydrogen peroxide. It was suggested that hydrogen sulfide formed in polymicrobial infections may play an important role in the host defense by potentiating the antimicrobial effect of hydrogen peroxide produced by phagocytic cells.     

Serum lipids and lipoproteins in relation to endogenous and exogenous female sex steroids and age. The Women's Health in the Lund Area (WHILA) study

BACKGROUND: Different studies have presented conflicting results concerning the effect of menopause on lipid levels. AIMS: To describe the serum lipid profile and the prevalence of hyperlipidemia in women aged 50-60 and the perceived relation to endogenous and exogenous hormones and age. METHODS: Out of a total population of 10,766 women aged 50-59 years, 6908 (64%) participated in a health assessment program, including a lipid profile evaluation. The women were grouped according to hormonal status into pre-menopausal (PM), post-menopausal without hormone replacement therapy (PM0) (HRT) and post-menopausal with hormone replacement therapy (PMT). Age groups used were 50-54, 55-59 and >60 years. RESULTS: Serum cholesterol and triglycerides increased significantly by age in PM0 (P < 0.0001) and triglycerides also in PMT (P < 0.0001). Serum high-density lipoprotein cholesterol (HDL) levels decreased significantly by age in PMT (P = 0.002) and low-density lipoprotein cholesterol (LDL) increased in PM0 (P < 0.0001) and PMT (P = 0.007). The co-prevalence of levels of cholesterol >7 and triglycerides >2 mmol/l decreased by age in PM, but increased by age in PM0 and PMT. The prevalence of high-risk lipid levels and the prevalence of coexisting additional two metabolic risk factors were higher in the PM0 compared to the PMT group. The prevalence of serum triglycerides >1.5 and serum cholesterol >5 mmol/l were increasing by age in each of the hormonal groups. CONCLUSIONS: These data suggest that loss of endogenous sex steroids contribute substantially to an increased atherogenic lipid profile. Hormone replacement therapy may partly reverse these differences.