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Biomedical subjects

E Eriksson

Publications and source records attributed to E Eriksson.

At least 271 records · Page 15Linked to original sources

The putatively selective dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 stimulate prolactin release in rats.

The 2-aminotetralin derivatives cis-(+)-(1S,2R)-5-methoxyl-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76, and cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, are novel centrally acting stimulants with a putative action as selective dopamine (DA) autoreceptor antagonists. In the present study these compounds were evaluated with respect to their effects on prolactin release in male rats. Both (+)enantiomers caused a pronounced increase in plasma prolactin levels in previously untreated animals. The effects of (+)-AJ 76 and (+)-UH 232 were virtually similar, except for a higher initial increase after the latter compound. In agreement with earlier reports, the reserpine-induced elevation of plasma levels of prolactin was strongly suppressed by the DA autoreceptor agonist B-HT 920. This effect of B-HT 920 was completely blocked by (+)-AJ 76 and by (+)-UH 232, indicating that both (+)enantiomers antagonize lactotroph DA receptors. The present findings support the notion that lactotroph DA receptors resemble DA autoreceptors rather than postsynaptic DA receptors. A possible difference between the auto-/lactotroph vs. postsynaptic DA receptors with respect to both the responsiveness to agonists and to the affinity of pure antagonists is discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Stereoselective inhibition of prolactin secretion by (-)-HW-165, a novel 3-PPP congener; further support for similarities between central DA autoreceptors and pituitary lactotroph DA receptors.

The novel atypical dopamine (DA) receptor agonist HW-165 (trans-7-hydroxy-1,2,3,4,4a,5,6,10b-octahydrobenzo(f)quinoline), a 'rigid' 3-PPP congener, and its enantiomers were investigated with regard to their actions on prolactin (PRL) release in rats. Racemic HW-165 dose dependently inhibited the elevation of PRL secretion induced by monoamine synthesis disruption (NSD 1015) combined either with abolished DA nerve impulse flow (GBL) or with monoamine depletion (reserpine). Racemic HW-165 was roughly equipotent to 3-PPP but 5-10-fold less potent than apomorphine. The PRL inhibitory action of racemic HW-165 was stereoselectively prevented by the DA antagonist (+)-butaclamol. Since the chiral aspect of lactotroph DA receptor activation by 'atypical' DA receptor agonists has not been covered in previous investigations the effects of the HW-165 enantiomers were now studied. Our findings suggest that the PRL inhibitory properties of racemic HW-165 reside in its (-) enantiomer, (+)-HW-165 being devoid of activity. Taken together, the results reinforce the concept that the pituitary lactotroph DA receptors mediating the inhibition of PRL release are similar, notably also from a stereochemical point of view, to central DA receptor sites with presumed high agonist sensitivity, such as DA autoreceptors.

4-Butyrolactone↗

Does alprazolam, in contrast to diazepam, activate alpha 2-adrenoceptors involved in the regulation of rat growth hormone secretion?

The conventional benzodiazepine diazepam and the novel triazolobenzodiazepine alprazolam were compared with respect to effects on growth hormone (GH) release in reserpine pretreated rats. The reserpine pretreatment was undertaken to eliminate brain monoaminergic influence on GH secretion, hence obtaining a low GH baseline from which a drug induced increase could be easily detected. Previous studies have indicated that activation of brain alpha 2-adrenoceptors is an indispensable prerequisite for GH release induced by other agents such as serotonin and opiate receptor agonists. In line with these findings, diazepam was found to induce GH release in reserpine pretreated rats only when the alpha 2-receptor agonist clonidine was simultaneously administered. In contrast, alprazolam caused a dose-dependent increase in plasma GH when given alone to reserpine pretreated rats. This effect of alprazolam was effectively antagonized by either of the two selective alpha 2-receptor antagonists yohimbine or idazoxane. The data indicate that alprazolam, but not diazepam, activates brain alpha 2-adrenoceptors involved in rat GH regulation. The possibility that an alpha 2-agonistic profile of alprazolam may contribute to the suggested effectiveness of the drug in the treatment of panic disorder is discussed.

Adrenergic alpha-Antagonists↗

Immunohistochemical localization of plasminogen activators in human saphenous veins.

Human saphenous veins were analyzed for presence of plasminogen activators (t-PA) in the endothelium of the vessel walls by immunohistochemical techniques. We used a polyclonal rabbit antihuman t-PA antibody, a monoclonal mouse-antihuman t-PA and a goat antibody to low molecular weight urokinase. To demonstrate presence of antigen we used FITC conjugated anti-IgG or the Biotin-Avidin technique. Both monoclonal and polyclonal anti-t-PA demonstrated positive fluorescence in the endothelial layer. Tests for urokinase were negative. The present study thus demonstrated that t-PA was present in the vascular endothelium. This is in accordance with data from earlier histochemical studies for detection of PA activity.

Endothelium↗

Sexually differentiated actions of 3-PPP enantiomers on prolactin secretion.

The ability of the enantiomers of the atypical dopamine receptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) to counteract gamma-butyrolactone-induced hyperprolactinemia was compared in male and female rats. Following gamma-butyrolactone (GBL) pretreatment serum prolactin concentrations were higher in female than in male rats. In males (-)-3-PPP tended to be somewhat less effective than (+)-3-PPP in decreasing serum prolactin concentrations (levels after (+)-3-PPP and (-)-3-PPP: 21% and 33%, respectively, of levels in GBL-pretreated control(s). In females the (-)-form induced a much weaker response than did the (+)-form (levels after (+)-3-PPP and (-)-3-PPP: 8% and 74%, respectively, of levels in GBL pretreated controls). Parallel experiments replacing GBL by reserpine yielded similar results. Data are discussed in terms of sex differences in responsiveness of pituitary dopamine receptors.

4-Butyrolactone↗

Microcirculation in muscle.

The microvascular architecture in muscle is reviewed herein. The intrinsic vasculature is similar in different muscles. There are numerous arterioarterial (100 microns diameter) and venovenous (150 microns) anastomoses creating a large microscopical network. End-arterioles (30 microns), end-venules (50 microns), and capillaries (6 microns) form a smaller microscopical network. There are no arteriovenous shunts. Precapillary arterial vessels larger than 10 microns have one or several layers of smooth muscle cells. There are no precapillary sphincters. Postcapillary vessels larger than 15 microns have one continuous layer of smooth muscle cells. Calculations show that the cross-sectional area is the smallest and hence resistance the greatest in arterioles of 22 microns and venules of 40 microns. There is better physiological support for giving plasma expanders, such as dextran, rather than vasodilators in low flow situations.

Animals↗

Burns in patients under 2 and over 70 years of age.

A total of 246 consecutive burn patients younger than 2 years and older than 70 years of age admitted to a burn center were reviewed retrospectively to study morbidity and mortality specific to these two age groups. Of these patients, 165 were less than 2 years of age and 81 were over 70 years of age, representing 16% and 8% of the total patient population respectively. In patients under 2, scald burns occurred in 127 (77%) and flame burns in 18 (11%). In patients over 70, flame was the most common burn mechanism, occurring in 64 (79%) patients, while scalds occurred in 12 (15%). The mean total body surface area (TBSA) burned in the younger age group was 13.2% (2.4% full thickness, 10.8% partial thickness) and in the older age group was 25% (12.8% full thickness, 12.2% partial thickness). Only 1 death occurred in the younger age group (0.6% mortality), while 41 deaths occurred in the older age group (50.6% mortality). If the burn involved a total body surface area greater than 40%, all patients died (100% mortality). A total of 36 complications occurred in the younger age group (0.2 complications per patient) and 111 in the older age group (1.4 per patient). Burn wound sepsis was the most common complication in each group, occurring in 28 patients under 2 and 42 elderly patients, and was responsible for the 1 death in the younger age group. Although burn wound sepsis was the most common complication in those patients over 70, cardiovascular and pulmonary complications were the most deadly, accounting for 68% (28 patients) of total deaths in this group.

Age Factors↗

Effect of temperature on blood flow and metabolism in a neurovascular island skin flap.

Using the buttock flap in 29 white Yorkshire pigs, blood flow and O2 consumption were measured at dermal temperatures between 35 degrees C and 15 degrees C. Flow was measured with an electromagnetic flowmeter and O2 consumption was calculated as the product of blood flow and the difference in flap A-VO2. Baseline flow was 6.6 +/- .9 (SE) ml/100 g/min at 35 degrees C and 3.1 +/- .02 (SE) ml/10 g/min at 15 degrees C. Blood flow through the flap stopped completely at a dermal temperature of 14 degrees C. Oxygen consumption was 0.16 +/- .02 (SE) ml/100 g/min at 35 degrees C and 0.04 +/- 0.01 (SE) ml/100 g/min at 15 degrees C. At 20 degrees C blood flow was 4.3 ml/100 g/min and metabolism was .04 ml/100 g/min. In other words, blood flow was 65% of baseline, while O2 consumption was only 25% of baseline. The therapeutic effect of local cooling at 20 degrees C deserves further investigation. The cessation of flow at 14 degrees C may be caused by increased plasma viscosity.

Animals↗

Changes in blood flow and metabolism in a neurovascular island skin flap after a burn.

In 8 male white Yorkshire pigs weighing approximately 42 kg each, 12 buttock neurovascular island skin flaps were dissected. Baseline recordings were made of blood flow and O2 consumption in the flap. Two series of experiments were carried out. In control animals (5), the flap was dissected and the "cold" aluminum plate was applied for 10 seconds. In the burned flaps (7) a contact burn of 2.68 calories/cm2 was created with a heated aluminium plate applied to the skin for 10 seconds. After this the flaps were studied for 4 hours. In the control flaps, blood flow and O2 consumption did not change. The burned flaps showed no change in blood flow, while O2 consumption increased significantly from .07 +/- .01 (SE) ml/100 g/min to .18 +/- .08 (SE) ml/100 g/min (p less than .05).

Animals↗

Experimental evaluation of tissue revascularization using a transferred muscular-vascular pedicle.

Skin and cartilage can be revascularized from a transferred muscular-vascular pedicle. Muscle vessels appear to connect with existing vessels in the subdermal plexus or perichondrium and determine the ultimate distribution of the skin or cartilage revascularized. The ideal timing for flap elevation following revascularization in this model is 21 to 28 days following transfer. Isolation of the muscular-vascular pedicle from underlying tissue by a silicone sheet does not appear to augment tissue revascularization. Delay procedures do not improve surviving flap length. Composite flaps of cartilage and skin can be revascularized using this technique.

Animals↗

Functional evaluation of latissimus dorsi donor site.

A study was undertaken to determine the cosmetic and functional problems associated with the latissimus dorsi muscle donor site. Twenty-four patients undergoing both free and pedicle muscle and myocutaneous flap procedures for a wide variety of reconstructive problems were studied. All patients had a contour defect at the donor site, a scar which varied with the patient's age and whether overlying skin had been taken with the muscle flap. Mild to moderate shoulder weakness and some loss of motion were noted in most patients which improved over the course of several months. An upper extremity disability in strength and shoulder motion should be anticipated following latissimus dorsi transfer, which in most cases is minimized by the recruitment of synergistic muscle units. Vigorous range-of-motion exercises following surgery should be encouraged to minimize adhesions and joint capsule stiffness. Social changes in occupation and daily living activities were noted which were not a problem for most patients. Twenty-three of 24 patients were pleased with the overall outcome of their surgery and would recommend the procedure to others. A prospective study before and after latissimus dorsi transfer followed by a second evaluation 2 to 3 years postoperatively would help to clarify the role synergistic muscle units play in "taking over" latissimus dorsi function.

Adolescent↗

Rejection of skin grafts and generation of cytotoxic T cells by mice depleted of L3T4+ cells.

In mice, "helper/inducer" T cells can be depleted by treatment with a rat monoclonal antibody to the cell surface antigen, L3T4, which is homologous to the human antigen T4 (CD4). In order to examine the contribution of "helper/inducer" T cells to cellular immunity, C57BL/6 (H-2b) mice were treated weekly with 1 mg i.v. of a monoclonal antibody to L3T4. Three days after the first injection, the mice received skin grafts from BALB/c (H-2d) mice. The mice were then examined for skin graft rejection and for the development of cytotoxic cells. Treatment with anti-L3T4 prolonged skin graft survival from 9 to 18 days. Graft rejection was associated with the development of cellular cytotoxicity against H-2d targets. Cytotoxicity developed despite greater than or equal to 90% depletion of splenic L3T4+ cells. Allospecific cytotoxic T cells could also be generated in vitro from C57BL/6 spleen cells depleted of L3T4+ cells, when these were exposed in a mixed leukocyte culture to irradiated, T-cell-depleted, BALB/c spleen cells. In a mixed leukocyte culture using responder spleen cells from untreated C57BL/6 mice, both proliferation and interleukin 2 production were inhibited in the presence of antibody to L3T4 and, to a lesser extent, by antibody to Lyt-2. Complete inhibition was achieved by the presence of both antibodies. In a mixed leukocyte culture using responder spleen cells from C57BL/6 mice that had been treated with anti-L3T4, both proliferation and interleukin 2 production were inhibited largely by antibody to Lyt-2, although the presence of both anti-Lyt-2 and anti-L3T4 was most inhibitory. These findings indicate that graft rejection and cellular cytotoxicity can be generated in mice depleted of L3T4+ cells by methods that have previously been shown to abrogate humoral immunity. Cellular immunity appears to require few, if any, L3T4+ cells. These findings have implications for the clinical use of antibodies to "helper/inducer" T cells.

Animals↗

Increase in muscular strength following surgery for primary hyperparathyroidism.

The muscle strength of the quadriceps muscle was measured in a computerized modified Cybex II muscle dynamometer. The method used is easy and has an error of greater than 5%. A marked increase in muscular strength was found after successful surgery for primary hyperparathyroidism (PHPT) with normalization of serum calcium levels. The results support the opinion that all patients with PHPT, with or without muscle weakness, should be recommended an operation if no serious contra-indications exist.

Adult↗

A central serotonin receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin, has different effects on prolactin secretion in male and female rats.

Male and female rats were compared with respect to alterations in prolactin secretion induced by the serotonin receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The dose-response curves after 8-OH-DPAT were irregular and had different shapes in the two sexes. In males, 0.1 and 0.3 mg/kg enhanced serum prolactin concentrations to about 200% of control values, whereas higher doses (1 and 3 mg/kg) had no effect on prolactin release. In females, in contrast, 0.1 mg/kg of 8-OH-DPAT tended to decrease serum levels of prolactin, while 0.3, 1, and 3 mg/kg elevated them in a dose dependent manner to maximally 700% of control values. The serotonergic agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (5 mg/kg), too, caused increased prolactin release in both sexes, and, again, females responded more forcefully. In males, but not in females, pretreatment with 8-OH-DPAT (1 mg/kg) reduced the 5-MeODMT-induced elevation of serum prolactin levels. The mechanism underlying the sexually differentiated effects of 8-OH-DPAT on prolactin secretion is discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Effects of naloxone on dental pain threshold following muscle exercise and low frequency transcutaneous nerve stimulation: a comparative study in man.

Previous studies have shown that muscle exercise and low frequency transcutaneous nerve stimulation (TNS) give rise to an analgesic effect in humans and animals. Endorphin has been proposed to mediate this analgesia. In this investigation, the effect of muscle exercise and low frequency TNS, on dental pain thresholds was studied and the possible involvement of endorphinergic mechanisms was investigated using naloxone as an antagonist. Dental pain thresholds were measured in 11 volunteers following leg or arm exercise and after low frequency TNS of the hands or face. After exercise (20 min) or stimulation (30 min) either 0.8 mg naloxone (2 ml) or saline (2 ml) was injected i.v. in a double-blind fashion. Pain thresholds were measured repetitively before and after exercise or stimulation. Both leg and arm exercise increased pain threshold. Stimulation of the hands also increased pain threshold, but less than arm exercise. A marked increase in pain threshold was seen after face stimulation. These changes in pain threshold were unaffected following injections of either naloxone or saline, except for an early and short-lasting reduction when naloxone was injected following arm exercise. The increases in pain threshold following muscle exercise and after low frequency TNS, showed similarities suggesting that a common mechanism might be involved. The pain threshold increase after arm exercise could only be partially mediated by endorphinergic mechanisms.

Adult↗

Calf muscle atrophy and muscle function after non-operative vs operative treatment of achilles tendon ruptures.

Fifteen operatively and eight non-operatively treated subcutaneous achilles tendon ruptures were randomly selected from 120 surgically and 35 non-surgically treated patients. Their calf muscle function was studied three to five years after treatment. Non-operatively treated patients were found to have a significantly impaired dynamic muscle function of the calf muscles when tested in a specially constructed heel-raise test device. Operatively treated patients did not show any significant impairment of their muscle function. Measurement of muscle area with CT-scanning showed a significant reduction of the calf muscle in the non-operatively treated patient while no such difference could be found in the operatively treated patients. Isokinetic muscle torque did not differ in the two groups of patients, thus Cybex-measurements do not seem to be a discriminating method in studying muscle function after achilles ruptures. On the basis of our findings we recommend that all athletes with achilles tendon ruptures be treated surgically. In non-athletes and older patients non-operative treatment might be considered.

Achilles Tendon↗

Diagnostic and operative arthroscopy of the hip.

Diagnostic and operative arthroscopies of the hip joint have been performed from an anterior approach after extension of the joint. The force needed to achieve a sufficient visualization of the hip joint was studied. In an anesthetized patient 300 Newtons (N) to 500 N was required, whereas up to 900 N was needed in an unanesthetized subject to achieve sufficient joint extension. Hip arthroscopy has been performed with a standard 5 mm Storz arthroscope. Alternatively, fluid and gas was used. It was possible to achieve good visualization of the anterior parts of the hip. Gas gave better information about the degree of degenerative arthritis while fluid was preferable for operative arthroscopy, eg, arthroscopic synovectomy. Synovial biopsies, removal of loose bodies, and partial arthroscopic synovectomy have been performed. The advantage was a very short time of rehabilitation. No serious complications occurred.

Adult↗