Association between gizzard lesions and increased caecal Clostridium perfringens counts in broiler chickens.

The aim of this study was to investigate the relationship between mucosal gizzard lesions and caecal Clostridium perfringens counts. Gross pathological changes in the gizzard and small intestine, and caecal C. perfringens counts from 1217 meat-type chickens were recorded during the course of six experiments and were statistically analysed. C. perfringens counts increased significantly (P < 0.001) with the severity of mucosal gizzard lesions. Mucosal gizzard lesions were more prevalent than necrotic enteritis. Correcting for the pen and necrotic enteritis within experiment, mucosal gizzard lesions explained 31.8% of the variation in C. perfringens counts. Mucosal gizzard lesions and age together explained 59.1% of the variation in C. perfringens counts. The mean ages of birds with moderate and severe mucosal gizzard lesions were 1.7 and 0.8 days lower than the mean age of birds with necrotic enteritis, respectively. The association between mucosal gizzard lesions and high C. perfringens counts might be of importance when attempting to improve production efficiency, health and the welfare of the chickens.     

Plasma protein haptoglobin modulates renal iron loading

Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme-iron recovery. We used haptoglobin-null mice to evaluate the impact of haptoglobin gene inactivation on iron metabolism. Haptoglobin deficiency led to increased deposition of hemoglobin in proximal tubules of the kidney instead of the liver and the spleen as occurred in wild-type mice. This difference in organ distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload.     

Blood flow in skin, subcutaneous adipose tissue and skeletal muscle in the forearm of normal man during an oral glucose load

Blood flow to the forearm, and the subcutaneous tissue and skin in the forearm were measured by strain gauge plethysmography, 133Xe-elimination and Laser Doppler flowmetry during an oral glucose load (I g glucose kg-1 lean body mass) and during control conditions. The forearm blood flow remained constant during both experiments. Glucose induced a two-fold vasodilatation in subcutaneous tissue. In skin, glucose induced a relative vasodilatation and later a relative vasoconstriction compared with control experiments. When estimated from forearm blood flow and subcutaneous and skin blood flows, muscle blood flow decreased about 20-30% during both experiments. Proximal nervous blockade did not abolish the glucose-induced vasodilatation in subcutaneous tissue. In the glucose experiment, arterial glucose concentration increased to 7.8 +/- 1.17 mmol l-1 30 min after the load was given and then decreased to 4.5 +/- 0.34 mmol l-1 at the end of the experiment. In the control experiments glucose concentration was constant. Arterial noradrenaline concentration increased significantly from 1.0 +/- 0.13 to about 1.5 +/- 0.3 nmol l-1 120 min after glucose and remained at this level during the experiment. Similarly adrenaline increased from 0.16 +/- 0.11 to about 0.4 +/- 0.16 nmol l-1 180 min after glucose. It is hypothesized that the vasodilating effect of glucose in subcutaneous tissue is secondary to metabolic events connected to glucose uptake and energy deposition in adipose tissue.     

Ultrastructural quantitation of atubular and hypertrophic glomeruli in rats with lithium-induced chronic nephropathy

Summary The very heterogeneous population of glomeruli in rats with lithium-induced chronic nephropathy which includes small glomeruli without connection to a proximal tubule (atubular glomeruli) and large hypertropic glomeruli with connection to a normal proximal tubule, was studied at the ultrastructural level, using stereological methods. After 8 weeks of lithium treatment followed by 8 weeks without lithium the hypertrophic glomeruli showed no changes in their relative ultrastructural composition, including normal mesangium, basement membrane-like material and peripheral basement membrane. The absolute quantities of each component were, however, increased due to the increased volume of the glomeruli. The atubular glomeruli had increased volume fractions of mesangium, peripheral basement membrane, basement membrane-like material and epithelium, whereas the absolute quantities were decreased due to the decreased volume. The thickness of the basement membrane was within normal limits in the group of hypertrophic glomeruli but increased by 31% above controls in the group of atubular glomeruli. Both groups of glomeruli in lithium-treated animals showed normal mean foot process width, but with a slightly abnormal distribution. The atubular glomeruli showed a disproportionate large decrease in peripheral filtration surface and capillary length, compared with the reduction in glomerular volume, whereas the hypertrophic glomeruli showed changes in proportion with the increased volume.     

The Heritability of Depression Symptoms in Elderly Danish Twins: Occasion-Specific Versus General Effects

Depression symptomatology was assessed up to four times at 2-year intervals on a sample of 2100 Danish twins initially aged 70 years and older. Data were analyzed using the biometric growth model approach proposed by Neale and McArdle (2000). Results show that occasion-specific depression is moderately and equally heritable in men and women (occasion-specific estimates of heritability ranged from 22% to 37%). Estimates of phenotypic variance, genetic variance, and heritability did not vary systematically across waves. In the best-fitting growth model, depression symptomatology was accounted for by two factors: (1) a level (i.e., average) effect that was highly heritable (estimate of 69% in women and 64% in men) and reflected overall vulnerability, and (2) a residual effect that was nonheritable and reflected occasion-specific circumstances that could either exacerbate or moderate inherited vulnerability. Attempts to identify specific genetic contributions to depression might profitably focus on average levels across multiple assessments, while attempts to identify specific environmental effects might profitably focus on deviations about this average.     

Selective immunolesion of cholinergic neurons leads to long-term changes in 5-HT2A receptor levels in hippocampus and frontal cortex

Although loss of cholinergic neurons in the basal forebrain is considered a key initial feature in Alzheimer's disease (AD), changes in other transmitter systems, including serotonin and 5-HT_2A receptors, are also associated with early AD. The aim of this study was to investigate whether elimination of the cholinergic neurons in the basal forebrain directly affects 5-HT_2A receptor levels. For this purpose intraventricular injection of the selective immunotoxin 192 IgG-Saporin was given to rats in doses of either 2.5 or 5 μg. The rats were sacrificed after 1, 2, 4 and 20 weeks. 5-HT_2A protein levels were determined by western techniques in frontal cortex and hippocampus. A significant 70% downregulation in frontal cortex and a 100% upregulation in hippocampus of 5-HT_2A receptor levels were observed 20 weeks after the cholinergic lesion when using the highest dose of 192 IgG-Saporin. Our results show that cholinergic deafferentation leads to decreased frontal cortex and increased hippocampal 5-HT_2A receptor levels. This is probably a consequence of the interaction between the serotonergic and the cholinergic system that may vary depending on the brain region.     

Gene expression of colony-stimulating factors and stem cell factor after myocardial infarction in the mouse

Recent studies have suggested that cytokines such as macrophage colony-stimulating factor (M-CSF) might be involved in the pathogenesis of ischaemic heart disease. Macrophage colony-stimulating factor, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-colony stimulating factor (GM-CSF), stem cell factor (SCF), interleukin-3 (IL-3) and interleukin-7 (IL-7) are potent cytokines belonging to the same structual class that may affect function, growth and apoptosis both in the heart and other organs. The aims of the present study were to characterize a post-infarction model in the mouse and to examine mRNA expression of M-CSF, GM-CSF, SCF, IL-3 and IL-7 during the development of heart failure. Myocardial infarction (MI) was induced in mice by ligation of the left coronary artery. Average infarct size was 40% and the mice developed myocardial hypertrophy and pulmonary oedema. Ribonuclease (RNAase) protection assays showed abundant cardiac expression of M-CSF and SCF. After MI, we measured down-regulation of cytokine mRNA expression in the heart (M-CSF, SCF), lung (M-CSF), liver (M-CSF) and spleen (M-CSF) compared with sham. Cardiac G-CSF, GM-CSF and IL-7 mRNAs were not detected. In conclusion, abundant cardiac gene expression of M-CSF and SCF was found. In our mouse model of MI, M-CSF and SCF were down-regulated in the heart and several other organs suggesting specific roles for these cytokines during development of ischaemic heart failure.