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Biomedical subjects

P Holm

Publications and source records attributed to P Holm.

At least 73 records · Page 4Linked to original sources
PubMed1996

Clinical relevance of serum nortriptyline and 10-hydroxy-nortriptyline measurements in the depressed elderly: a multicenter pharmacokinetic and pharmacodynamic study.

In a recent placebo-controlled multicenter study, 38 patients, ranging in age between 62 and 88 years (median, 71) were treated with nortriptyline (NT) for up to 7 weeks. NT was administered in a divided dose of 75 mg daily and serum NT (se NT), and its 10-hydroxy-metabolites (se OH-NT) were determined at various intervals. Several clinical measures of efficacy, including the 17-item Hamilton Rating Scale for Depression, were evaluated weekly as well as side effects (anticholinergic) and electrocardiogram (ECG) changes. Eighty-one percent of patients had NT levels in the previously defined therapeutic range of 50 to 170 ng/ml, with steady state reached between 1 and 3 weeks. There was little individual variation in drug kinetics and metabolism over the study period. In general se OH-NT levels were not greater than those of se NT. Pharmacodynamic analyses showed that patients with moderate to severe anticholinergic side effects [CSE(+)] had significantly higher NT levels than those with mild or no symptoms [CSE(-)]. Furthermore, repeated-measures ANOVA modeled over time showed a highly significant decrease in clinical measures in both CSE groups of patients and also a highly significant group-time interaction. Higher se OH-NT levels were associated with less anticholinergic side effects. No ECG changes were observed.

Aged↗
PubMed1996

The endothelin antagonist bosentan: hemodynamic effects during normoxia and hypoxic pulmonary hypertension in pigs.

In this study, we investigated the hemodynamic effects and receptor-blocking properties of the nonselective endothelin antagonist bosentan in pigs during normoxia and acute hypoxia. Hypoxic pulmonary hypertension was induced by decreasing the fraction of inhaled oxygen to 0.1. In a control group of pigs, hemodynamic parameters proved to be stable through 2 hours of hypoxia. Infusions of endothelin-1, endothelin-3, and sarafotoxin 6c into the pulmonary artery resulted in pulmonary and systemic vasoconstriction during normoxia, whereas endothelin administration during hypoxic pulmonary hypertension resulted in pulmonary vasodilation. After administration of bosentan, the vasopressor effect of endothelin-1 during normoxia was significantly attenuated and the pulmonary vasodilatory effect of endothelin-1 during hypoxia was reduced. Furthermore, the development of hypoxic pulmonary hypertension was significantly reduced by bosentan. In contrast, bosentan did not influence the pulmonary vasopressor response to the thromboxane mimic U-46619. We therefore conclude that vasopressor endothelin receptors seem to be activated by endogenous endothelin released during hypoxia, leading to an increase in the pulmonary vascular tone.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Tissue concentrations of endothelins and functional effects of endothelin-receptor activation in human arteries and veins.

In the present study, the tissue content and functional effects of endothelin-1 and endothelin-3 were examined in human vessels of importance in coronary bypass operations. Human coronary arteries (i.e., the left anterior descending coronary artery) were obtained from eight cardiac valve donors within 6 hours after death, pulmonary arteries were perioperatively obtained from 15 patients operated on because of lung tumors, and internal thoracic arteries and great saphenous and cephalic veins were obtained at coronary bypass operations from a total of 28 patients. Endothelin-1 and endothelin-3 content was quantified by radioimmunoassay. For functional experiments, the vessels were mounted in organ baths for recordings of isometric contractions in response to endothelin-1, endothelin-3, and the endothelinA-receptor agonist sarafotoxin 6c. In all vessels investigated, the endothelin-1 content was higher than that of endothelin-3. The highest levels were found in the left anterior descending coronary artery, followed in declining order by the internal thoracic artery, pulmonary artery, saphenous vein, and cephalic vein. Endothelin-1 contracted all vessels in a concentration-dependent fashion. This effect was enhanced in the left anterior descending and internal thoracic arteries by inhibition of nitric oxide and prostaglandin formation. The contractile effect was attenuated in a concentration-dependent fashion in all vessels by incubation with the endothelinA-receptor blocker BQ-123. Furthermore, contractions evoked by endothelin-1 in the left anterior descending coronary and pulmonary arteries were antagonized by the combined endothelinA- and endothelinB-receptor blocker bosentan. Endothelin-3 contracted the left anterior descending coronary and pulmonary arteries and the saphenous vein, but not the internal thoracic artery, in a BQ-123-sensitive fashion. However, after inhibition with nitric oxide or prostaglandin, endothelin-3 also contracted the internal thoracic artery, and the response in the left anterior descending coronary artery was enhanced. Sarafotoxin 6c evoked a BQ-123-sensitive contraction of the left anterior descending coronary artery. It is concluded that endothelinA receptors mediate the major portion of the vasoconstriction observed on exposure to endothelin-1, endothelin-3, and sarafotoxin 6c in the left anterior descending coronary, pulmonary, and internal thoracic arteries and the saphenous vein. Furthermore, endothelinB-receptor activation, with subsequent formation of nitric oxide or prostaglandin (or both), counteracts the vasoconstrictor response to endothelin in the left anterior descending coronary and internal thoracic arteries, but not in the pulmonary artery or saphenous vein. The present findings therefore suggest that endothelinA-receptor antagonism might prove beneficial in preventing possible endothelin-induced coronary graft spasm.

Adult↗
PubMed1996

Nitric oxide-donating properties of mesoionic 3-aryl substituted oxatriazole-5-imine derivatives.

1. The nitric oxide (NO)-releasing properties of two new mesoionic 3-aryl substituted oxatriazole-5-imine derivatives (GEA 3162 and GEA 3175) were characterized and compared with the known NO-donors 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). 2. GEA 3162, GEA 3175, SIN-1 and SNAP inhibited adenosine 5'-diphosphate-induced platelet aggregation (IC50 values 0.18, 0.39, 3.73 and 2.12 microM, respectively). All four compounds induced a dose-dependent and more than 4 fold increase in cyclic GMP in platelets. The increase in cyclic GMP concentration was potentiated more than 1.5 fold by a phosphodiesterase inhibitor, zaprinast (10 microM) and inhibited 38-97% by oxyhaemoglobin (10-45 microM). 3. All of the four compounds studied converted oxyhaemoglobin to methaemoglobin and formed a paramagnetic NO-haemoglobin complex. All but GEA 3175 formed nitrite and nitrate in phosphate buffer. During a 40 min incubation, GEA 3162, SIN-1 and SNAP (100 microM) produced 50-70 microM NO2- + NO3- as determined by high performance liquid chromatography. The release of NO and NO2 by GEA 3175 was increased 140 fold in the presence of human plasma (0.14 and 19.7 ppb in the absence and presence of 1% human plasma, respectively) as analyzed by ozone chemiluminescence. 4. The results suggest that the mesoionic 3-aryl substituted oxatriazole-5-imine derivatives GEA 3162 and GEA 3175 as well as SIN-1 and SNAP release nitric oxide.

Blood Platelets↗
PubMed1996

Embryo viability, duration of gestation and birth weight in sheep after transfer of in vitro matured and in vitro fertilized zygotes cultured in vitro or in vivo.

The influence of various in vitro procedures on embryo survival and the production of normal offspring was investigated in sheep. Zygotes produced from in vitro matured (IVM) and fertilized (IVF) oocytes derived from slaughtered Merino ewes were allocated to three culture treatments for 6.5 days. Two groups were cultured in vitro in the absence or presence of oviduct epithelial cells while the third group was cultured in vivo in the oviducts of synchronized ewes. A fourth group of zygotes obtained from superovulated Merino ewes was also cultured in vivo and served as controls. After culture, IVM-IVF morulae and blastocysts, and control embryos were transferred to final recipient ewes. Pregnancy was diagnosed at day 50 of gestation by ultrasonography and pregnancies were allowed to go to term. The survival to term of IVM-IVF zygotes cultured in vitro was reduced compared with both in vivo cultured IVM-IVF zygotes and control zygotes (25-35% versus 51-60%, respectively, P < 0.05). Day 6.5 IVM-IVF morulae had a lower survival rate than did control morulae regardless of culture treatment (P < 0.05), while survival rates of day 6.5 IVM-IVF blastocysts cultured in vivo did not differ from those of control blastocysts (P > 0.1). Both the gestation period and birth weight of IVM-IVF lambs were increased when compared with controls, the former significantly in all groups (154.0-154.9 days versus 150.6 days; P < 0.01), while the latter increase was on the borderline of significance (4.5-4.8 kg versus 4.0 kg; 0.01 < or = P < or = 0.1, respectively) and dependent on the prolongation of the gestation period. It is concluded that in vitro maturation and fertilization compromise subsequent embryonic and fetal development in sheep irrespective of the subsequent in vivo or in vitro culture treatment. Subjecting IVM-IVF zygotes to in vivo culture for 6.5 days minimizes only some of these effects, thus leading to the aberrant production of some offspring.

Animals↗
PubMed1995

Relative importance of ischemic injury and immunological injury on the development of transplant arteriosclerosis in rabbit aortic allografts.

The development of transplant arteriosclerosis has emerged as a major problem to long-term survival after heart transplantation. The accelerated development of arteriosclerosis in the transplanted arteries, including the aorta, could result either from an ischemic injury in connection with the transplantation, or from an immunological reaction against the transplant, or both. We evaluated histologically and biochemically whether extension of the ischemic period from 1 to 24 hr has any influence on the development of transplant arteriosclerosis, in aorta-allografted rabbits clamped at human levels of plasma cholesterol. One set of rabbits was without immunosuppressive treatment (n = 10 + 9) and another otherwise identical set of rabbits received cyclosporine to achieve blood cyclosporine levels in the human therapeutic range (n = 10 + 12). The number of T lymphocytes in intima suggested that, in the grafts from untreated animals, an immunological injury had arisen, which cyclosporine reduced. A clear trend toward a worsening of the transplant arteriosclerosis was demonstrated as a function of the severity of the ischemic injury, both with and without immunosuppressive treatment. However, the worsening effect of maximal ischemic injury was less than that due to maximal immunological injury. In grafts from cyclosporine-treated animals, the development of transplant arteriosclerosis was significantly less than in grafts from untreated animals exposed to identical periods of ischemia. These results suggest that compared with immunological injury, ischemic injury is of minor importance for the development of experimental transplant arteriosclerosis.

Animals↗
PubMed1995

Moclobemide and nortriptyline in elderly depressed patients. A randomized, multicentre trial against placebo.

Moclobemide and nortriptyline were compared with placebo in a double-blind randomized multinational (Canada, Denmark and UK) trial comprising 109 patients of > 60 years of age with major depression (DSM-III-R). Patients were randomized to 7 weeks of treatment with doses of 400 mg/day moclobemide, 75 mg/day nortriptyline or placebo. It was necessary to adjust nortriptyline dosage in < 20% of patients to maintain serum levels within the postulated therapeutic window of 50-170 ng/ml. At end of treatment, the remission rates were 23% for moclobemide, 33% for nortriptyline and 11% for placebo. Anticholinergic and orthostatic events occurred more often with patients on nortriptyline than either moclobemide or placebo.

Aged↗
PubMed1995

Effect of oestrogen replacement therapy on development of experimental arteriosclerosis: a study in transplanted and balloon-injured rabbit aortas.

The mechanism underlying possible protection of oestrogen replacement therapy against cardiovascular disease appears to go beyond beneficial changes in plasma lipoproteins. A direct action of oestrogen on the metabolism of lipoproteins after entering the arterial wall may occur. The present study evaluated whether oestrogen replacement therapy affects the development of experimental arteriosclerosis in immunologically injured (experiment A + B) and balloon-injured (experiment B) aortas in ovariectomized rabbits maintained at a human level of plasma cholesterol; both models involve severe damage to the endothelium with resulting rapid accumulation of lipoproteins in the arterial intima and therefore appear suitable for studying factors directly affecting subendothelial lipoprotein metabolism. In experiment A, dietary cholesterol required to maintain a human level of plasma cholesterol was significantly higher for the oestrogen group than for the placebo group. Similarly, cholesterol accumulation in the aortic grafts was borderline higher for the oestrogen than the placebo group, whilst intimal hyperplasia was without difference between the groups. Due to a modified schedule of cholesterol feeding in experiment B, oestrogen and placebo groups received the same amount of dietary cholesterol, and cholesterol accumulation and intimal hyperplasia were similar in immunologically injured and balloon-injured parts of the aorta in both groups. These results suggest that in the female rabbit maintained at a human level of plasma cholesterol, oestrogen replacement therapy has no direct action on the development of experimental arteriosclerosis when induced by immunological or mechanical injury to the endothelium.

Animals↗
PubMed1995

Effect of the antioxidant probucol on transplant arteriosclerosis in aorta-allografted rabbits.

The attenuation of atherogenesis by oral probucol treatment, demonstrated in several animal studies, has been attributed to the antioxidative property of probucol. It is thought that probucol, by inhibiting oxidation of low density lipoproteins (LDL) decreases the uptake of LDL into monocytes, and thereby reduces the development of foam cells and fatty streaks. Also, the neointimal proliferation seen after balloon injury has been attenuated by treatment with probucol. Since foam cells and neointimal proliferation are both important elements of transplant arteriosclerosis, we have investigated whether probucol might also retard the development of experimental transplant arteriosclerosis. The thoracic aorta from one rabbit was transplanted as a bypass graft onto the abdominal aorta of another rabbit. Nine rabbits were treated with 1 g probucol per day and seven animals were treated with vehicle. After a recovery period of 2 weeks, all rabbits were clamped at a human level of plasma cholesterol (6 to 7 mmol/l) for a period of 3 weeks. The amount of dietary cholesterol necessary for this clamping tended to be higher in probucol treated than in vehicle-treated rabbits. The distribution of plasma cholesterol between lipoprotein classes was similar in the two groups, except for the concentration of high density lipoproteins (HDL), which was significantly lowered by probucol. Probucol markedly decreased the susceptibility of LDL and intermediate density lipoprotein plus very low density lipoprotein (IDL + VLDL) particles to oxidation, as measured by the production of conjugated dienes when adding Cu2+. Despite this, the development of transplant arteriosclerosis as well as the number of macrophages in the neointima were not significantly different in the aortic allografts from the two groups. These results suggest that antioxidative agents do not retard the development of experimental transplant arteriosclerosis.

Animals↗
PubMed1995

Endothelin infusion reduces hypoxic pulmonary hypertension in pigs in vivo.

Previous work has shown that the plasma levels of the potent vasoactive peptide endothelin (ET) are increased in pathophysiological conditions with increased pulmonary vascular resistance and it has been speculated that ET may play some part in hypoxic pulmonary hypertension. We have therefore evaluated the effects of ET-infusion in the porcine pulmonary circulation after hypoxia-induced hypertension. Pits under general anaesthesia were artificially ventilated through an endotracheal tube and hypoxia was induced by decreasing the fraction inhaled O2 from 0.21 to 0.10. Haemodynamic parameters were continuously recorded using a Swan-Ganz catheter in combination with thermodilution for cardiac output measurements. ET-1 or ET-3 was given as an i.v. infusion through the Swan-Ganz catheter in the right ventricle. Hypoxia induced a reproducible increase in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (MPAP) and right ventricular stroke work (RVSW) while the systemic vascular resistance (SVR) slightly decreased. Cumulative infusion of ET-1 (10, 25 and 50 ng kg-1 min-1) dose-dependently decreased MPAP and PVR; at a higher dose (100 ng kg-1 min-1), the PVR returned to the level observed at hypoxia. ET-infusions at 50 and 100 ng kg-1 min-1 evoked an increase in SVR and a decrease in cardiac output (CO) and stroke volume (SV). RVSW also gradually decreased during ET-1 infusion. Infusion of ET-3 evoked effects similar to those of ET-1 infusions, although the response to ET-3 was not that rapid in onset. In a second series of animals, repeated 15 min periods of hypoxia evoked a stable, reproducible response with a consistent increase in PVR, MPAP and RVSW which returned to baseline values during normoxia. Infusion of ET-1 (25 ng kg-1 min-1) evoked a rapidly developing decrease in PVR and MPAP which was quickly normalized upon cessation of the ET-infusion. ET-1 infusion at this concentration did not per se influence the haemodynamic parameters during normoxia. It is concluded that in the pig, short-term ET-infusion reduces the pulmonary hypertension associated with acute hypoxia.

Animals↗
PubMed1994

Effect of sheep and human follicular fluid on the maturation of sheep oocytes in vitro.

This study examines the effect of sheep and human follicular fluid on the in vitro maturation (IVM) of sheep follicular oocytes. Oocyte cumulus complexes recovered post mortem were matured for 24 to 26 h at 38.6 degrees C, 5% CO(2) in air, in TCM-199 bicarbonate medium supplemented with 20% fetal calf serum (FCS) and, where stated, with maturation hormones, including FSH (5.0 microg/ml), LH (5.0 microg/ml) and estradiol (1 microg/ml), or with sheep follicular fluid recovered from large (>5 mm) or small (2 to 5 mm) ovarian follicles post mortem, or with human periovular follicular fluid obtained during routine IVF procedures. The matured oocytes were then denuded, and their maturation stage and developmental capacity were assessed by in vitro fertilization (IVF) and culture (IVC). It was found that inclusion of sheep or human follicular fluid or hormone supplements in the IVM media more than doubled the number of oocytes completing maturation (FCS alone 33%, compared with 76.2% for maturation hormones, 84.2% for fluid from large and 69.6% for fluid from small sheep follicles and 82.6% for human follicular fluid), and significantly increased fertilization rates (FCS alone 51.6%, compared with 71.9% for maturation hormones, 78.4% for fluid from the large and 75.7% for fluid from small sheep follicles and 73.1% for human follicular fluid) without discernible adverse effects on the development of the cleaving embryos to the morula or blastocyst stage in culture. Omission of FCS and supplements from the IVM medium resulted in a marked reduction (56%) in the number of oocytes maturing. This reduction could be offset to a large part, but not completely, by inclusion of human follicular fluid or human follicular fluid plus LH (5 microg/ml) in the medium. The results of this study show that addition of sheep or human follicular fluid to maturation medium can enhance rather than inhibit the maturation and fertilizability of sheep follicular oocytes in vitro.

Journal Article↗
PubMed1993

"Project lifestyle" and new forms of living for the mentally retarded in the local community.

Since 1890, representatives of the Ministries and Departments of Social Security in Norway, Sweden, Finland, Iceland and Denmark have been working to create a foundation and a framework for a common Scandinavian research and development project concerning the quality of life of the mentally retarded. In 1992, with financial support from The Nordic Council of Ministers, the exchange of information and the building up of a network was begun, involving those taking part in some 50 development projects in Scandinavian countries. The project has focussed on three themes central to efforts made on behalf of and with the cooperation of mentally retarded people in these countries: the mentally handicapped person in the local community, independence and the quality of life, and communication. The aim of the project is to establish a Scandinavian network of key persons in the field, to systematize and propagate promising developments and to cast light on differences and similarities between various Scandinavian models for research and development related to the mentally retarded.

Activities of Daily Living↗
PubMed1992

Elevated uptake of low density lipoproteins by human lung cancer tissue in vivo.

In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. Previous in vitro and in vivo studies have shown that acute myelogenous leukemia cells have elevated receptor-mediated uptake of low density lipoproteins (LDL), compared to normal WBC. High receptor-mediated uptake of LDL by certain cancer cells in tissue culture and experimental tumors in animals in vivo has also been demonstrated. The present study was undertaken to compare the in vivo assimilation of LDL by human lung cancer tissue with that by surrounding lung tissue. Ten patients with newly diagnosed lung tumors, scheduled for surgery, received an i.v. injection of [14C]sucrose-labeled LDL. Following cellular uptake and degradation of the LDL particle, the radiolabeled sucrose moiety remains trapped in the lysosomal compartment, making this labeling technique useful for in vivo studies of tissue uptake of LDL. Radioactivity was determined in plasma and in tissue biopsies obtained at surgery 1-3 days after injection. The uptake of radioactivity in lung cancer tissue was elevated (1.5-3.0-fold), compared to surrounding tissue, in 7 of 9 patients with primary lung cancer. The most rapid preoperative disappearance of radioactivity from plasma was found in 2 patients with large tumors exhibiting high LDL uptake, relative to normal lung tissue. These findings support the hypothesis that the selectivity of cytotoxic agents can be enhanced also in nonhematological malignancies by administering the drugs incorporated in LDL particles.

Adult↗
PubMed1992

Moclobemide and placebo in mild major depression: a double-blind randomized trial.

Sixty-eight patients participated in this double-blind randomized study with moclobemide versus placebo (35 allocated to moclobemide; 33 to placebo). In terms of mean HAMD total scores, improvement tended to be more pronounced in the moclobemide group at treatment end-point. Efficacy was judged to be 'very good' or 'good' in 50% of moclobemide-treated patients and in 27% of placebo-treated patients: in completers only, the difference was more marked (69% versus 33%; P less than 0.05 Mann-Whitney test). Tolerability was judged to be 'very good' or 'good' in 77% of moclobemide-treated patients and in 94% of placebo-treated patients. Adverse events were observed in 31% of patients in the moclobemide group and in 18% of patients in the placebo group.

Adult↗
PubMed1992

Pregnancies and live birth from in vitro fertilization of calf oocytes collected by laparoscopic follicular aspiration.

Oocytes were recovered by laparoscopic aspiration from 3- to 8-week-old calves treated with follicle-stimulating hormone (FSH) followed by human chorionic gonadotropin (hCG) to induce follicular growth and oocyte maturation in vivo. Most of the recovered oocytes either had resumed meiotic maturation at the time of aspiration or were competent to undergo maturation during subsequent culture in vitro. Oocytes matured in vivo following FSH and hCG treatment underwent in vitro fertilization (70%) at rates not significantly different from those of control oocytes recovered from adult cow ovaries at abattoirs and matured in vitro (75%). Calf oocytes that were immature at aspiration exhibited lower fertilization rates after in vitro maturation (36%) but their rate of development to morulae and blastocysts did not differ from that of mature oocytes at aspiration. A total of 91% of the zygotes produced from calf oocytes developed to morula and 27% to blastocyst stages during 6 days of culture. The proportion developing to morulae was significantly higher (P<0.05) than that observed for zygotes resulting from in vitro maturation and fertilization of oocytes recovered from cow ovaries obtained at an abattoir and processed concomitantly (59% to morulae and 18% to blastocysts). Morulae or blastocysts developed from oocytes from 5 to 6-week-old calves, when transferred to synchronized recipient heifers, resulted in 2 confirmed pregnancies, one of which produced a single full-term live calf. The ability to produce embryos from oocytes recovered from newborn or prepubertal calves offers the potential for markedly reducing the generation interval in cattle, thereby substantially accelerating the rate of genetic gain that can be achieved through embryo transfer.

Journal Article↗
PubMed1992

Hemorrhagic infarct conversion in experimental stroke.

STUDY OBJECTIVE: This study investigated the relations between hemorrhagic infarction and occlusion, release, levels of glycemia, brain energy state, and lactate content after cerebrovascular occlusion. DESIGN: Prospective, controlled laboratory investigation. TYPE OF PARTICIPANTS: One hundred six pentobarbital-anesthetized cats. INTERVENTIONS: The middle cerebral artery was occluded with a Yasargil clip transorbitally either temporarily (0.5, four, and eight hours) or permanently. Normoglycemic and hyperglycemic animals were closely monitored for eight hours. Brain pathology was assessed after two weeks' survival or at the time of spontaneous animal death. Topographic brain metabolite studies were carried out after four hours of middle cerebral artery occlusion. MEASUREMENTS AND MAIN RESULTS: Morphometric quantitation of cerebral hemorrhage and infarction and fluorometric determinations of blood and brain tissue, glucose, glycogen, lactate, adenosine triphosphate, and phosphocreatine from 16 topographic brain sites were carried out. Twenty-one of 82 (25.6%) animals evaluated neuropathologically showed hemorrhagic infarcts. Occluding the artery in hyperglycemic animals caused fivefold more frequent and 25-fold more extensive hemorrhage into infarcts than in normoglycemic animals. Temporary occlusion with clip release after four hours in hyperglycemic animals caused the most extensive hemorrhage into infarcts. Most hemorrhages into infarcts (81%) took place in animals that died within a few hours after they experienced ischemia and that showed infarction and marked edema of the entire middle cerebral artery territory. Linear regression analyses demonstrated a close relation between hemorrhage into infarcts and near-total energy depletion (adenosine triphosphate, less than 0.3 microM/g; phosphocreatine, less than 0.5 microM/g) in brain sites that showed extremely high tissue lactate concentrations (more than 30 microM/g). The biochemical changes that correlated with hemorrhage into infarcts were more marked than those with infarcts without hemorrhage. CONCLUSION: Hyperglycemia and restoration of blood flow to ischemic territories were strong risk factors for hemorrhagic infarct conversion. Concomitant tissue metabolic changes suggest that marked tissue energy depletion accompanied by acidosis damages brain vessels and renders them penetrable for edema fluid and, ultimately, red blood cell extravasation.

Adenosine Triphosphate↗
PubMed1991

Treatment of lichen planus with acitretin. A double-blind, placebo-controlled study in 65 patients.

Sixty-five patients with lichen planus were included in a multicenter trial of acitretin. At the end of an 8-week placebo-controlled, double-blind phase, a significantly higher number of patients treated with 30 mg/day acitretin (64%) showed remission or marked improvement compared with placebo (13%). Furthermore, during the subsequent 8-week open phase, 83% of previously placebo-treated patients responded favorably to acitretin therapy. Typical retinoid adverse reactions were present in all patients on active drug. Laboratory studies did not show any clinically significant changes. This study shows that acitretin is an effective and acceptable therapy for severe cases of lichen planus.

Acitretin↗