Excess prevalence of extracranial carotid artery lesions in renovascular hypertension.

High renin hypertension has been associated with a higher risk of stroke than low-to-normal renin hypertension. Accordingly, we investigated prospectively the prevalence of the extracranial carotid artery lesions in a case-control study of 70 patients (38 women and 32 men, aged 16 to 77 years) without history or symptoms of cerebrovascular disease. Renovascular hypertension was diagnosed in 35 patients on the basis of the angiographic demonstration of renal artery stenosis and of the favorable outcome after revascularization. It was caused by atherosclerosis in 20 patients and by fibrodysplasia in 15. Each renovascular hypertensive patient was individually matched with a control with primary hypertension for sex, race, age, blood pressure levels, duration of hypertension, smoking, diabetes mellitus, total serum cholesterol, and triglycerides. Carotid arteries were evaluated by a High Resolution Duplex system (Biosound 2000, probe 4 cm, 8 mHz). Our results show that after the matching the two groups were similar in terms of demographic features and overall cardiovascular risk profile (all P = NS). In renovascular hypertensives the prevalence of carotid artery lesions (82.6%) was significantly (P less than .01) higher than in primary hypertensives (42.9%). The higher prevalence of lesions in renovascular hypertension was observed not only in patients with atherosclerosis (100% v 55%, P less than .001), but also in those with fibrodysplasia (57% v 27%, P less than .01). Thus, for the same demographic features and overall cardiovascular risk profile, renovascular hypertension carries a more detrimental effect on the carotid artery than primary hypertension.     

The effects of vitamin D binding protein-macrophage activating factor and colony-stimulating factor-1 on hematopoietic cells in normal and osteopetrotic rats

Osteopetrosis is a heterogeneous group of bone disorders characterized by the failure of osteoclasts to resorb bone and by several immunological defects including macrophage dysfunction. Two compounds, colony-stimulating factor-1 (CSF-1) and vitamin D-binding protein- macrophage activating factor (DBP-MAF) were used in the present study to evaluate their effects on the peritoneal population of cells and on cells within the bone marrow microenvironment in normal and incisors absent (ia) osteopetrotic rats. Previous studies in this laboratory have demonstrated that administration of DBP-MAF to newborn ia animals results in a substantial increase in bone marrow cavity size due to upregulated osteoclast function. To study the effects of these compounds on the macrophage/osteoclast precursors, DBP-MAF, CSF-1, and the combination of these compounds were given to newborn ia and normal littermate animals. Both the normal and mutant phenotypes responded similarly when treated with these compounds. Rats exhibited a profound shift toward the macrophage lineage from the neutrophil lineage when compared with vehicle-treated control animals after treatment with these compounds. In the in vivo peritoneal lavage study, animals received injections of CSF-1, DBP-MAF or DBP-MAF/CSF-1 over a 4-week period. The various types of cells in the peritoneal cavity were then enumerated. The in vitro study consisted of cells isolated from the bone marrow microenvironment and cultured on feeder layers of CSF-1, DBP-MAF, or DBP-MAF/CSF-1 for colony enumeration. The increase in macrophage numbers at the expense of neutrophil numbers could be seen in both the in vivo and in vitro experiments. The macrophage/osteoclast and neutrophil lineages have a common precursor, the granulocyte/macrophage colony-forming cell (GM-CFC). With the addition of CSF-1, the GM-CFC precursor may be induced into the macrophage/osteoclast lineage rather than the granulocyte lineage. This increased pool of cells in the macrophage/osteoclast lineage can be functionally upregulated with the subsequent addition of DBP-MAF to perform the activities of phagocytosis and bone resorption. The in vitro data also showed that DBP-MAF did not support colony development as in CSF-1 or the combination treatment. The recruitment and activation of cells into the macrophage/ osteoclast lineage may help to correct the bone and immune defects found in diseases demonstrating a significant lack of myeloid cells, as well as neutrophilia disorders and the disease, osteopetrosis.     

Prague women's drinking before and after the 'velvet revolution' of 1989: a longitudinal study

Results are presented of a follow-up study in which a representative sample of 608 Prague women aged 20–49 years in 1987 at first interview was re-interviewed in 1992 3 years after the revolution that ended the 41 years of the Communist era in Czechoslovakia. The average yearly consumption of alcohol in the followed-up female sample increased between 1987–92 from a reported 3.6 litres to 4.8 litres. The percentage of heavier drinkers (with average daily consumption of over 20 g alcohol) increased from 7.2% to 14.0%. The women expressed increased tolerance of drunkenness in their attitudes to drinking. The consumption increase was mainly due to increased drinking frequency of spirits and to increased quantity of beer consumed per occasion. The consumption increase was largest in women working as free-lance and the newly emerging self-employed women; economically inactive women did not increase their consumption. Women who reported a positive impact of the socio-political changes on their personal lives and an expansion of social contacts also reported larger than average consumption increases. A coincidence of stressful, possibly self-inflicted, life events and increased alcohol use was observed and interpreted as probably a two-way influence.     

Oxidative stress and delta-ALA-D activity in chronic renal failure patients.

In this paper, we studied the influence of uremia and hemodialysis on oxidative parameters and delta-aminolevulinic acid dehydratase (delta-ALA-D) activity in control subjects, patients with chronic renal failure (CRF) on hemodialysis treatment (HD) and in patients not undergoing hemodialysis (ND). An increased lipid peroxidation was observed in the serum of HD and ND patients, as measured by the MDA serum levels. However, the level of MDA from erythrocytes was only elevated in HD patients. Blood catalase activity was increased in HD and ND groups. This study also showed a decreased activity of blood delta-aminolevulinic acid dehydratase (delta-ALA-D) in both groups of patients. This study demonstrated a positive correlation between ALA-D activity and hemoglobin, suggesting that inhibition of this enzyme might enhance anemia in CRF. A negative correlation was found between the alteration in delta-ALA-D activity and oxidative stress, which may indicate that the inhibition of ALA-D can be used as an index of oxidative stress.     

Neonatal treatment with 192 IgG-saporin produces long-term forebrain cholinergic deficits and reduces dendritic branching and spine density of neocortical pyramidal neurons

The role of basal forebrain-derived cholinergic afferents in the development of neocortex was studied in postnatal rats. Newborn rat pups received intraventricular injections of 192 IgG-saporin. Following survival periods ranging from 2 days to 6 months, the brains were processed to document the cholinergic lesion and to examine morphological consequences. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the cholinergic neurons in the medial septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ hybridization for glutamic acid decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a marked reduction of the cholinergic axons in neocortex. Cholinergic axons are reduced throughout the cortical layers; this reduction is more marked in medial than in lateral cortical areas. The thickness of neocortex is reduced by approximately 10%. Retrograde labeling of layer V cortico-collicular pyramidal cells reveals a reduction in cell body size and also a reduction in numbers of branches of apical dendrites. Spine densities on apical dendrites are reduced by approximately 20-25% in 192 IgG- saporin-treated cases; no change was detected in number of spines on basal dendrites. These results indicate a developmental or maintenance role for cholinergic afferents to cerebral cortical neurons.      

ACUTE BUT NOT CHRONIC ANGIOTENSIN-CONVERTING ENZYME INHIBITION INDUCES ENZYME SYNTHESIS IN THE GLOMERULUS OF THE SPONTANEOUSLY HYPERTENSIVE RAT

1. Treatment with angiotensin-converting enzyme (ACE) inhibitors slows the rate of progression of nephropathy in the spontaneously hypertensive rat (SHR) with streptozotocin-induced diabetes. Paradoxically, however, chronic ACE inhibitor therapy has been reported to be associated with induction of ACE in the plasma. We sought to determine whether induction also occurred in the glomerulus. 2. Seven days after induction of diabetes rats were randomized to receive perindopril (4mg/kg per day) in the drinking water or water alone. Blood glucoses were maintained 6–10 mmol/L by daily ultralente insulin. Rats were killed after 1 and 12 weeks of ACE inhibitor therapy and the kidneys were harvested. Angiotensin-converting enzyme activity was determined in isolated glomeruli before and after removal of perindopril and reconstitution with zinc sulphate. 3. After 1 week of ACE inhibitor therapy, glomerular ACE was significantly greater after removal of perindopril than either before its removal (P < 0.025) or in the untreated controls (P < 0.025). After 12 weeks of therapy, ACE activity was significantly lower in the perindopril-treated group than in the untreated controls (P < 0.025). There was no increase in ACE activity following removal of perindopril. 4. These studies suggest that short-term ACE inhibition is associated with induction of ACE in the glomerulus. However, there was no increase in ACE activity after removal of perindopril, suggesting that induction of synthesis of this enzyme in the glomerulus does not occur during chronic ACE inhibition.     

EVIDENCE FOR DIRECT INTERACTION OF KETAMINE WITH α- AND β2-ADRENOCEPTORS

1. Ketamine has a number of effects that suggest that it may interact with α- and β-adrenoceptors. To date, the experimental evidence for this has been indirect and has been based on physiological studies using competitive blocking agents. In the present study we sought to determine from receptor binding studies whether ketamine binds directly to α- and β-adrenoceptors. 2. Membrane preparations o. α₁- and β₂-adrenergic binding sites were obtained from urinary bladder and urethrae of sheep. These binding sites were characterized by saturation analyses using [³H]-prazosin for α₁-adrenoceptor binding sites and [¹²⁵I]-cyanopindolol (CYP) for the β₂-adrenoceptor binding sites. The receptors were further characterized by displacement studies using selective and non-selective antagonists. 3. Studies in which ketamine was used to displac. [³H]-prazosin revealed a K_d of 3.40±1.23× 10^?3 mol/L for ketamine binding to ai-adrenoceptors. Displacement studies of [¹²⁵I]-CYP by ketamine showed a K_d of 0.35±0.03× 10^?3 mol/L for ketamine binding to β₂-adrenoceptors. 4. We conclude that ketamine interacts directly with both ai- an. β₂-adrenoceptors and that such interactions probably explain the reported effects of this agent on the vasculature and the bronchial tree.