Distribution of Apolipoprotein E Isoforms between Very Low and High Density Lipoproteins of Normal Subjects and Hyperlipidemic Patients with Special Reference to Type III Hyperlipidemia

ABSTRACT Serum very low (VLDL) and high density lipoproteins (HDL) from 17 hyperlipidemic patients and 10 normal subjects have been isolated by preparative ultracentrifugation, and the electrophoretic patterns of apolipoprotein E (apo E) isoforms in the lipoproteins have been examined by isoelectric focusing. Type III hyperlipidemia (dyslipoproteinemia) has been suggested to be a disease caused by an abnormal mutant of the apo E-3 isoform. In accordance with this, all patients with type III hyperlipidemia in the present study showed lack of apo E-3 in VLDL. However, all these patients demonstrated a protein zone corresponding to apo E-3 in their HDL fraction. Patients with other types of hyperlipidemia or normal subjects who showed an apo E-4 variant in VLDL had an HDL that lacked apo E-4. The results support the hypothesis that type III hyperlipidemia is due to an abnormal composition of the VLDL particles rather than a result of an abnormal mutant of apo E-3.     

Periodontal healing following experimental injury to root surfaces of human teeth

abstract – The healing of mechanically traumatized alveolar bone, periodontal membrane, cementum and dentin was studied in relation to the vitality of the tooth. Cavities were made in the vestibular root surfaces of 88 human teeth (44 vital teeth, 20 root-filled teeth and 24 nonvital not-root-filled teeth). The cavities were prepared at a distance from the gingival crevices to avoid contamination of the wound from microbial plaque during the healing process. At the end of the observation period (varying between 7 and 593 d) the teeth were removed together with vestibular bone and gingiva and examined histologically. The first sign of cementum formation was seen 23 d after surgery. When the observation period exceeded 40 d, areas of newly formed cellular cementum were noted on the dentin surfaces of most of the teeth. The statistical analysis did not show any differences in healing pattern between the three groups studied.     

Periodontal healing of exarticulated monkey teeth stored in milk or saliva

Abstract – Saliva has usually been recommended as a storage medium for exarticulated teeth. Recent tissue culture studies have, however, shown that milk has a more suitable osmolaliry than saliva and that milk is a bettter storage medium for human periodontal ligament cell. In the present investigation periodontal healing of replanted monkey teeth has been studied after storage of teeth in milk or saliva before replantation. There was much less root resorption, especially inflammatory resorption, after storage in milk thatn in saliva. Storage of teeth in milk for 3 h before replantation resulted in the same low frequence of root resorptions as was seen after immediate replantation. There was hardly any replacement resorption (ankylosis) seen in the replanted teeth.     

Mitoses and microorganisms in the periodontal membrane after storage in milk or saliva

Abstract – Milk and saliva were tested in vitro as potential storage media for avulsed teeth. Developing monkey teeth were extracted and stored in milk or saliva for periods ranging from l to 6 h. The osmolality, pH, conductivity and number of viable bacteria in the media were determined after predetermined intervals during the storage periods. After the storage periods the teeth were either prepared for scanning electron microscopy or cultured for 24 h in Eagle's medium supplemented with ³H-thymidine. In the scanning electron microscope numerous adherent bacteria were seen covering the periodontal membrane after storage in saliva but none were found after storage in milk. The cultured teeth were sectioned and evaluated with autoradiography. Superficial parts of the periodontal membrane were rapidly injured by storage in saliva while the epithelial root sheath and the apical pulpal cells were affected at a later stage. Cells neighboring the cementoblasts incorporated ³H-thymidine after 6 h storage in milk but not after storage in saliva for the same length of time. It was concluded that the low osmolality in combination with bacteria which adhered to the periodontal membrane made saliva less suited than milk for long time storage of avulsed teeth. Furthermore, a viable layer of cells close to the root surface seemed to be a prerequisite for a successful healing without root résorption after replantation.     

Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein-lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy

Abstract. Twenty-one patients with increased, thyroid-stimulating-hormone (TSH) concentrations in the serum while fasting were studied before and after substitution with l-thyroxine. Nine patients had TSH values < 40 mU/1 and an average serum-thyroxine value of 64 nmol/1. Twelve patients with TSH-values > 40 mU/1 had an average serum-thyroxine value of 23 nmol/1. On treatment TSH and thyroxine normalized (reference limits < 8 mU/1 and 65–160 nmol/1 respectively) as did also the response to a load with thyroid-releasing hormone (TRH). In the group with severe thyroid dysfunction (TSH > 40 mU/1) the lipoprotein-lipase activities in both adipose and skeletal-muscle tissue were subnormal before therapy and increased during substitution treatment. This was also reflected in a significant increase of the post-heparin, lipoprotein-lipase activity in the plasma and of the fractional removal rate of an i.v. injected fat emulsion. Ten out of twelve patients showed a decrease of the triglyceride concentration in whole serum, which reflected changes of the triglyceride concentrations in low-density lipoproteins (LDL) and high-density lipoproteins (HDL) more than changes in very-low-density lipoproteins, in which the triglyceride concentration was unchanged during treatment. In LDL, both the cholesterol and triglyceride concentrations were elevated before therapy and decreased by 22% and 32% of the pretreatment values, respectively, during treatment. Furthermore, the serum-apolipoprotein-B concentration decreased by 16%. The serum-apolipoprotein-A-I concentration was subnormal before treatment and the lipid composition of the HDL particle was changed towards an enrichment of triglycerides. During treatment, the HDL-triglyceride concentration decreased, whereas that of HDL cholesterol was unchanged. The fasting serum-insulin concentration increased significantly during the treatment period. In the group with mild hypothyroidism (TSH < 40 mU/1), there were no significant changes similar to those found in severe hypothyroidism.     

Lidocaine and Nisoldipine Attenuate Almokalant-Induced Dispersion of Repolarization and Early Afterdepolarizations In Vitro

Attenuation of Almokalant-Induced Proarrhythmias In Vitro. Introduction: Treatment with Class III antiarrhythmic agents may lead to increased dispersion or repolarization and early afterdepolarizations (EADs), which are both likely substrates for torsades de pointes. Recent studies in vivo have shown that the prevalence of proarrhythmias induced by Class III agents may be reduced by Na⁺ or Ca²⁺-blocking agents. In the present study, tentative mechanisms for this protective effect were investigated in vitro. Methods and Results: Transmembrane action potentials were recorded simultaneously from rabbit isolated ventricular muscle (VM) and Purkinje fibers (PF). At a basic cycle length (BCL) of 500 msec, the Class III agent almokalant (0.1 μM) increased the dispersion by prolonging the action potential duration (APD) significantly more in the PF (33%± 4.2%, n = 18) than in the VM (17%± 5.9%, n = 18. P < 0.05). In six of the preparations, addition of 1, 5, and 25 μM lidocaine reduced the almokalant-induced prolongation in a concentration-dependent manner mainly in the PF, thereby decreasing the dispersion. At 5 μM lidocaine, the remaining prolongation was 7%± 12.2% (P < 0.05 vs time controls) in the PF and 14%± 6.4% in the VM, respectively. In six other preparations, the addition of 0.01, 0.05, and 0.25 μM nisoldipine did not reduce the almokalant-induced prolongation in the PF and VM, hut attenuated the spike-and-dome appearance of the action potential in the PF. In separate experiments performed at a BCL of 1000 msec, EADs developed in 2 of 6 and 5 of 6 PF during superfusion with almokalant (0.3 and 1 μM, respectively) at an API) of 828 ± 41.4 msec. In six separate preparations pretreated with lidocaine (5 μ) the almokalant-induced prolongation in the PF was less pronounced and EADs were not observed. Pretreatment with nisoldipine (0.05 μM) did not influence the response to almokalant, and in 4 of 6 preparations the APD exceeded 1000 msec. Despite this extensive prolongation, EADs did not appear. Conclusion: At concentrations that did not affect the APD in the VM hut reduced the APD in the PE. lidocaine suppressed almokalant-induced dispersion and the development of EADs. Nisoldipine, (m the other hand, inhibited almokalant-induced EADs directly. Hence, (he primary APD-prolonging effect of a Class III agent may he preserved, but the risk of proarrhythmary reduced, during concomitant treatment with low concentrations of a Na⁺- or Ca²⁺ blocking agent.     

Erythropoietin and Renin Substrate in Cerebellar Haemangioblastoma

ABSTRACT. We examined eight cerebellar haemangioblastoma tumours from eight patients, aged 16–63 years, 5 females and 3 males. Preoperative haemoglobin values exceeded 180 g/1 in four patients, and 150 g/1 in four. All high Hb values were normalized upon surgical removal of the tumours. All tumours contained scattered cells which stained positively with antisera against pure human urinary erythropoietin and plasma renin substrate. We conclude that cerebellar haemangioblastomas produce immunoreactive erythropoietin, which shares common antigenic determinants with renin substrate.     

A novel mutant variant of the CYP2D6 gene (CYP2D6 17) common in a black African population: association with diminished debrisoquine hydroxylase activity

1The debrisoquine hydroxylase (CYP2D6) is polymorphically distributed. Not only are there differences in the proportions of extensive metabolisers to poor metabolisers in various ethnic groups, but there are also pronounced variations in the metabolic capacity among those classified as extensive metabolisers. 2The mean debrisoquine metabolic ratio of Caucasian extensive metabolisers is lower than that for a number of African populations. In the present study, we have searched for novel CYP2D6 mutations to explain the diminished enzyme activity in African populations. 3Three Zimbabwean Shona subjects with EM phenotypes (metabolic ratios for debrisoquine of 0.4, 1.5 and 10.5 respectively) were selected and the open reading frame of the CYP2D6 gene of each was sequenced. 4The subject with metabolic ratio of 10.5 was found to be homozygous for an allele with a nucleotide exchange in exon 2, ¹¹¹¹C→T causing a ¹⁰⁷Thr→Ile amino acid exchange in a conserved region of the enzyme. In addition, he was homozygous for the ²⁹³⁸C→T and ⁴²⁶⁸G→C mutations causing ²⁹⁶Arg→Ser and ⁴⁸⁶Ser→Thr amino acid substitution found in the CYP2D6*2 allele. 5Seventy-six Zimbabwean Shona subjects were subsequently genotyped for the ¹¹¹¹C→T mutation and for the intron 1 gene conversion present in the CYP2D6*2 gene. The ¹¹¹¹C→T mutation was found at an allele frequency of 34% and was only present in alleles carrying the gene conversion in intron 1 indicative for the CYP2D6*2 gene. 6This allele (CYP2D6*17), containing the ¹¹¹¹C→T, ²⁹³⁸C→T and ⁴²⁶⁸G→C mutations, was found to be strongly associated with lower capacity for debrisoquine hydroxylation. We therefore postulate that the CYP2D6*17 allele might contribute to the molecular basis of the previously established diminished debrisoquine hydroxylase activity in African Bantu populations.     

Inadvertent Transarterial Pacemaker Insertion: An Unusual Complication

We describe an unusual complication of pacemaker treatment in a patient who died after a replacement operation. In a difficult situation in which a functioning pacemaker was highly desirable and in which most of the available veins had already been used, the pacemaker electrode was inserted, by mistake, through a small artery. This was not detected by fluoroscopy during surgery. The postoperative X-ray examination seemed to indicate that the electrode tip was located in the coronary sinus, but the subsequent autopsy revealed it to be located in the left ventricle.