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Biomedical subjects

V Manninen

Publications and source records attributed to V Manninen.

At least 109 records · Page 6Linked to original sources

Effect of diazepam on endothelial permeability, plasma lipids and lipoproteins in cholesterol fed rabbits.

In order to investigate the effect of diazepam in reducing the incidence and severity of cholesterol induced atherosclerosis in rabbits, 3 treatment groups were compared. The control Group I received the laboratory diet alone. Group II received cholesterol (1 gm daily, given by syringe). Animals in Group III additionally received diazepam (3 mg/kg/day) orally, again by syringe. After 21 days, animals were injected with Evans blue and 3 hours later their aortas were removed and examined for permeability changes. Serum was assayed for various lipid and lipoprotein components. Cholesterol feeding produced a 10-fold increase in serum cholesterol values in Groups II and III compared to the control Group I. The aortic uptake of Evans blue was significantly increased in animals treated with cholesterol but not in those which simultaneously received diazepam. Thus, diazepam prevented the increased endothelial permeability produced by hypercholesterolaemia, but it is not yet clear whether this effect involves the central nervous system or is a consequence of some more local membrane stabilizing action.

Animals↗

Effect of administration of activated charcoal and fibre on absorption, excretion and steady state blood levels of digoxin and digitoxin. Evidence for intestinal secretion of the glycosides.

The effects of activated charcoal and fibre on absorption and stationary plasma levels of digoxin and digitoxin have been studied. The effect of fibre alone is small but an interactive effect on absorption may occur if fibre and digoxin are ingested simultaneously. Charcoal effectively decreases glycoside absorption even when administered after the glycosides. During maintenance therapy with digoxin or digitoxin, charcoal administration decreased the glycoside plasma levels by 31.2% and 18.3% respectively. It is suggested that even digoxin may have a significant biliary excretion and enterohepatic circulation or that this glycoside has a significant intestinal secretion. The therapeutic implication of this study is that charcoal may be of value, not only in the management of acute glycoside poisoning, but also in some cases of more chronic intoxication.

Adult↗

Influence of a psyllium-based fibre preparation on faecal and serum parameters.

A fibre made of psyllium husk was given to 12 elderly patients for 4 months in order to investigate their faecal output and selected serum parameters. The fibre significantly improved bowel function and faecal output confirming its value as a non-irritant, harmless bulk-forming laxative. Serum cholesterol was decreased by 20% while triglycerides remained unchanged. There was a significant reduction in serum calcium after withdrawal of the fibre supplement. There were no significant changes in serum iron, total iron binding capacity, fibrinogen, or in the haematological parameters (ESR, haemoglobin, leucocyte count) attributable to the fibre. The high phytate content of the fibre does not appear to have any clinically significant effect on mineral absorption. It is suggested that dietary fibre (at least psyllium-based fibre preparations) may have significant cholesterol lowering capacity due to the binding of bile-acids in the intestine.

Aged↗

Plasma prekallikrein, kallikrein inhibitors, kininogen and lipids during gemfibrozil treatment in type II dyslipidaemia.

The effects of gemfibrozil on plasma prekallikrein, kallikrein inhibitors, kininogen and plasma lipids were investigated in 31 male subjects having either type IIA or IIB dyslipidaemia. During gemfibrozil use, plasma prekallikrein and kininogen were increased significantly while kallikrein inhibitors increased only slightly. Total cholesterol and triglycerides decreased while HDL cholesterol was increased. Changes in prekallikrein and HDL cholesterol were correlated, whereas no other significant correlations between changes in lipid and kinin parameters were seen. The observed changes in prekallikrein and kininogen possibly indicate a shift in the thrombo-haemorrhagic balance in favour for increased fibrinolysis. If so, the effects of gemfibrozil in prevention and management of atherosclerosis would not be solely due to correlation of the dyslipidaemia but also to protection against the accelerated coagulation tendency seen in type II dyslipidaemia.

Adult↗

Studies on hypoxic dyslipidaemia. Effect of lipid modulating drugs.

Haemorrhagic anaemia, exposure to altitude and depression of cell respiration are known to increase plasma triglyceride and cholesterol levels. The common triggering mechanism in all 3 instances is oxygen deficiency but mode of action is not known. The present study was intended to investigate whether lipid lowering drugs clofibrate or gemfibrozil could counteract such hypoxic dyslipidaemia in rats induced by altitude exposure. It was unexpectedly found that in normal rats gemfibrozil elevated plasma total cholesterol with an increase in the HDL-cholesterol component whereas clofibrate caused a rise in LDL-cholesterol. Nicotinic acid had no consistent effect. In hypoxia control rats showed an increase in cholesterol and triglyceride level. Both gemfibrozil and clofibrate prevented the rise of triglycerides. Total cholesterol fell in rats treated either with gemfibrozil or clofibrate during altitude exposure, indicating that neither natural nor gemfibrozil-augmented hyper-HDL-aemia could be maintained during oxygen deficiency.

Altitude↗

Kidney and liver function in rats during the edema following constriction of thoracic inferior vena cava with and without adrenalectomy or hypophysectomy.

In several animal species, constriction of the thoracic inferior vena cava (TIVCC) is known to increase proximal sodium reabsorption and inhibit natriuresis following saline loading, leading to edema. To eluicidate the role of adrenal and hypophyseal hormones in the development of edema, kidney and liver functions after TIVCC were compared in adrenalectomised or hypophysectomised rats, and in intact controls. It was found that edema (body weight increase) and kidney and liver affliction were much less pronounced after the operations. The roles of aldosterone and ADH deficiency in renal sodium and water excretion are discussed. It is concluded that adrenal and hypophyseal hormones do not initiate edema but modulate its extent. The absence of edematous changes in the liver of hypophysectomised and adrenalectomised rats deserves further attention.

Adenosine Triphosphatases↗

Trial with human leucocyte interferon and vidarabine in herpes simplex virus encephalitis: diagnostic and therapeutic problems.

A combination therapy of human interferon, vidarabine, and dexamethasone was administered to six patients with proven (Patients I-III) or presumed (Patients IV-VI) herpes simplex virus encephalitis (HSVE). Interferon combined with dexamethasone was given to one patient with presumed HSVE (Patient VII). Leucopenia and elevated serum transaminase levels appeared in all patients and a diffuse bleeding in one of them. Patients II, III and IV died, 26, 43, and 209 days after the onset of encephalitis, respectively. Patients I, V, VI, and VII were left with moderate brain damage although their physical condition was good. HSV encephalitis presents diagnostic difficulties, complementary diagnostic methods are needed, and current therapeutic trials must be considered as preliminary.

Adult↗

Tumefactive liver infiltration in amyloidosis.

A case of tumefactive liver infiltration in primary amyloidosis is presented. Both liver radionucleotide scanning and selective liver angiography indicated a local mass (8 X 15 cm) in the right liver lobe, but at laparotomy no liver tumour was found. The liver was enlarged. It was pale and firmer than usual. Liver biopsy specimens showed that about 30% of the liver mass was formed of amyloid deposited mainly between the liver cells in the perisinusoidal space. Adjacent lymph nodes were histologically normal. Amyloid was later found in a kidney biopsy, but a rectal biopsy showed no amyloid. 1.5 years later the patient is reasonably well, further ruling out the likelihood of neoplastic or malignant liver involvement. Echo studies of the liver showed only generalized enlargement with no focal region, indicating usefulness of this technique in diagnosing liver disease.

Aged↗

Effects of different progestogens on lipoproteins during postmenopausal replacement therapy.

To study the effects of different types of progestogens on lipoprotein metabolism, we treated three groups of postmenopausal women (six subjects each) for three weeks with estradiol valerate, 2 mg per day, and continued the treatment with different sequential estradiol-progestogen regimens as follows: Group A received norethindrone acetate, 10 mg per day, from Day 15 to Day 24 of the cycle; Group B, medroxyprogesterone acetate, 10 mg per day; and Group C, norgestrel, 0.5 mg per day. These regimens were followed by two consecutive cycles. Total cholesterol decreased in all groups by 10 to 18 per cent from the base-line values (P < 0.05). High-density-lipoprotein (HDL) cholesterol decreased by 20 per cent from the base-line level during treatment with both the estradiol-norethindrone acetate (P < 0.05) and estradiol-norgestrel (P < 0.01) regimens, whereas estradiol with medroxyprogesterone acetate was not associated with a significant change in HDL cholesterol. Our results suggest that the androgenic progestogens of the 19-nortestosterone series reverse the beneficial effect of postmenopausal estrogen treatment on HDL cholesterol, whereas the hydroxyprogesterone derivative medroxyprogesterone acetate has no such effect.

Cholesterol↗

Lack of serum cholesterol-lowering effect of skimmed milk and butter milk under controlled conditions.

The effects of skimmed milk and butter milk on the plasma concentration of cholesterol, triglyceride and high density lipoprotein cholesterol were studied in voluntary male prisoners under carefully controlled conditions. No significant differences were observed in the serum lipid or lipoprotein levels between the groups ingesting the control diet and the diets containing 2.71 of skimmed milk or 2.01 of butter milk per day for 3 weeks.

Animals↗

Gemfibrozil in the treatment of dyslipidaemias in middle-aged male survivors of myocardial infarction.

The effects of gemfibrozil on serum lipids and apolipoproteins were investigated in 60 male survivors of myocardial infarction (MI) (age range 29-48 years, mean 44). Fifteen had normal serum cholesterol (less than or equal to 7.0 mmol/l) and triglyceride (less than or equal to 1.7 mmol/l) levels, but most had low levels of high density lipoprotein (HDL) cholesterol (less than 1.00 mmol/l). Ten had type II A, 27 type II B and 8 type IV hyperlipidaemia. A double-blind placebo-controlled cross-over design was used with 3-month treatment periods. Gemfibrozil was given in daily doses of 1200 mg. The drug was well tolerated and there were no drop-outs attributable to its use. In all subjects, gemfibrozil reduced the mean serum total cholesterol by 17% and triglycerides by 54% and increased HDL cholesterol by 16%. The percentage HDL cholesterol of total cholesterol increased from 14 to 19%. The changes were similar in patients with normal serum cholesterol and triglyceride values and in those with classical hyperlipidaemias. In contrast, the changes during placebo treatment corresponded to those in healthy male untreated controls who were followed simultaneously. Apoprotein A-I remained unchanged, but A-II increased by 20% during gemfibrozil treatment. It is concluded that gemfibrozil corrects effectively dyslipidaemias in male MI patients but further long-term studies are warranted.

Adult↗

Effect of membrane potential on the passive transport of Tl+ in human red blood cells.

It was earlier found that Tl+ can easily penetrate the red cell membrane. The main finding of this work is that Tl+ can be used for studying alterations in the membrane potential of human red blood cells exposed to various experimental conditions. It was shown that after inhibiting active transport by ouabain, both the rate of trans-membrane movement and the cell/medium distribution of Tl+ were in a good agreement with the expected changes in membrane potential. Alterations in membrane potential were induced by modifying the cation permeability of the red cell membrane and by varying the cation concentration gradient across the membrane, which were achieved: 1) by incubation in an electrolyte-free sucrose solution. 2) by addition of valinomycin or 3) by addition of propranolol. Changes in cation permeability were followed by means of 86Rb tracer. Hyperpolarization of the red cell membrane led to accelerated influx and retarded efflux of Tl+. The opposite effect was obtained by depolarization. Quantification of the results was made using the Nernst equation and the cell/medium concentration ratio of Tl+ at equilibrium. The calculations show that the membrane potential of the propranolol-treated cells increased to about -20 mV, negative inside. The mechanism of the propranolol effect is briefly discussed.

Biological Transport↗

Effect of extracellular potassium on the loss of potassium from human red blood cells treated with propranolol.

The Ca++-dependent propranolol-induced increase of K+ permeability of human red blood cells, well documented in previous studies, was found to depend on extracellular K+. This was shown by studying the passive transport of 86Rb and the loss of bulk cellular K+ in both K+-free and K+-containing media. The maximal effect of propranolol was achieved with 5-10 mM K+ in incubation media. The external K+ could be substituted with Tl+, but not with Na+. When added after propranolol, extracellular K+ failed to initiate the effect of propranolol on membrane permeability. The cell/medium distribution of permeant 204Tl showed that the propranolol-induced increase of K+ permeability did not result in considerable hyperpolarization of the red blood cell membrane. The data obtained seem to be more consistent with a counter-transport model for explaining the propranolol effect than with a mechanism based on free diffusion of K+ through the membrane.

Cell Membrane Permeability↗

Acute encephalitis. A survey of epidemiological, clinical and microbiological features covering a twelve-year period.

The 191 adult patients with acute encephalitis who attended the Department of Neurology, University Hospital, Helsinki, during the 12-year period 1967-78, were analyzed for epidemiological, clinical, and microbiological features. Young healthy adults of either sex under 30 years of age were the most susceptible. The duration of symptoms varied from some hours to more than one month (less than or equal to 5 days in half of the patients). Prodromal symptoms were observed in 37.7%, meningeal signs or symptoms in 93.2%, features indicating brain involvement in 84.3% and clear effects on consciousness in 27.7% of the patients. Half (50.8%) recovered, while 43 (22.5%) were left with at least moderate disability after the acute phase. Twelve patients (6.3%) died. Lower socioeconomic status and age over 35 years were associated with increased mortality. The 10 patients with proven or presumptive herpes simplex virus (HSV) etiology had a mortality of 40% and only one recovered satisfactorily. There were 14 further cases suggestive of HSV. Mumps, Coxsackie B, adeno, and measles were the most frequent identifiable causes after HSV. Other etiological factors, including bacteria, appeared occasionally. The etiology remained obscure in 58.6% of the cases.

Adolescent↗

Herpes simplex virus encephalitis: new diagnostic and clinical features and results of therapy.

Six patients with herpes simplex virus (HSV) encephalitis underwent diagnostic and clinical evaluation. The HSV or its antigenic material was found in three brain biopsy specimens. In the remaining three cases, the diagnosis was supported by detection of HSV antibodies in the CSF. Cell count and total protein concentration in the CSF reached a maximum level at three weeks and two months, respectively. The IgG index and HSV antibody level in the CSF often remained constant after reaching maximal values. In three patients, a transient low serum sodium level was observed. Characteristic EEG changes were present five to 11 days after the onset of symptoms. Computerized tomographic scanning revealed a temporal low-density lesion. Three patients became deeply comatose and had respiratory failure. The patient without vidarabine therapy and one of the five patients treated with vidarabine died.

Antibodies, Viral↗

Effects of danazol and lynestrenol on serum lipoproteins in endometriosis.

The treatment of endometriosis with danazol or lynestrenol decreased cholesterol content of plasma high-density lipoproteins by 50% and 32%. There were simultaneous increases in low-density lipoprotein cholesterol content of 51% and 19%. We suggest that changes induced by lynestrenol are due to progestational activity, while in the case of danazol both antigonadotropic and androgenic activities are involved.

Adult↗