Effect of cholestasis induced by organic anion on the lipid composition of hepatic membrane subfractions and bile in rats

Several organic anions inhibit the secretion of cholesterol and phospholipid into bile without affecting total bile acid secretion (uncoupling). The uncoupling induced by sulphobromophthalein (BSP) alters the fatty acid composition of biliary lecithin. The purpose of this study was to investigate the relationship between the lipid composition of bile and of liver subcellular membrane fractions during BSP-induced uncoupling. After depletion of the bile salt pool, rats fitted with a bile duct cannulus were infused with sodium taurocholate given either alone or with BSP. Bile was collected and liver microsomes and canalicular membranes were isolated for analysis of lipid composition. In bile, uncoupling increased the cholesterol/phospholipid ratio (C/P ratio) and the saturated/unsaturated fatty acid ratio (S/U ratio) in phosphatidylcholine. The C/P ratio was increased in the canalicular membrane, but the membrane phosphatidylcholine S/U ratio decreased during uncoupling. In microsomes, the S/U ratio of membrane phosphatidylcholine was slightly increased, but the C/P ratio was unaffected during uncoupling. These results support the hypothesis that an increased secretion of hydrophobic phosphatidylcholine species from the canalicular membrane into bile reduces the proportion of hydrophobic phosphatidylcholine species in the canalicular membrane during uncoupling. The decreased contribution of hydrophobic phosphatidylcholine species may ameliorate the decrease in membrane fluidity resulting from the accumulation of cholesterol in the canalicular membrane and stimulate the synthesis of hydrophobic phosphatidylcholine species in the microsomes.     

Experience with a Novel Retrograde Wiring Technique for Coronary Chronic Total Occlusion

Objectives

We report our evaluation of a novel retrograde wiring technique known as the Rendezvous method.

Background

Different strategies of retrograde approaches can be used to improve the success rate of recanalization of coronary chronic total occlusion (CTO). We previously introduced the Rendezvous technique as an alternative final step for a retrograde CTO procedure.

Methods

From July 2007 to May 2010, 20 CTO patients were treated in two medical centers using the Rendezvous method, which is an alternative to the conventional final externalization method to complete the retrograde CTO procedure. It involves crossing of the guidewire through the CTO segment using 2 microcatheters.

Results

The majority of the CTO sites were in the proximal right coronary artery (50.0%). Most of the lesions had mild to moderate calcification (95.0%) and revealed an abrupt stump with a side branch at the occlusion site. The lesion length of the occlusion was relatively long (median 27.6 mm; range of 7.1–87.3 mm). No adverse cardiac events occurred during hospitalization.

Conclusion

The Rendezvous method used during the retrograde approach can be performed as an alternative to the conventional “externalization method” after the guidewire and microcatheter have crossed the occluded proximal segment into the opposite guiding catheter. (J Interven Cardiol 2013;26:254–258)

     

Idiopathic Reentrant Right Ventricular Outflow Tract Tachycardia With Presystolic Potential of Central Pathway

Idiopathic Reentrant RVOT VT With Presystolic Potential . A 12‐year‐old girl with recurrent palpitation due to idiopathic ventricular tachycardia (VT) with a left bundle branch block configuration and inferior axis was referred to our hospital. During the VT, a spiky presystolic potential (SP) was recorded at the septum of right ventricular outflow tract (RVOT) just below pulmonary valve. The SP was entrained with a decremental property by pacing from right ventricular apex. Concealed entrainment was observed by pacing where the SP was recorded. Delivery of radiofrequency current targeting the SP abolished the VT. The SP with the decremental property could represent the central pathway of this idiopathic RVOT reentrant VT. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1174‐1177)     

Crystal structure and molecular conformation of achatin-I (H-Gly-d-Phe-Ala-Asp-OH), an endogenous neuropeptide containing a d-amino acid residue

In order to investigate the active conformation of achatin-I (H-Gly-d -Phe-Ala-Asp-OH), an endogenous neuropeptide from the Achatina fulica ganglia, its crystal structure and molecular conformation were analysed by the X-ray diffraction method. Crystals from methanol/dioxane are monoclinic, space group P2₁ with a=5.083(1), b= 9.125(1), c= 20.939(3) Å, β=94.73(1)° The structure was solved by direct methods and refined to R = 0.051 for 1714 independent reflections with Fo > σ(Fo). The molecule exists as a zwitterion with the Gly N-terminal end protonated and Asp β-carboxyl deprotonated; the C-terminal of Asp is in a neutral state. The molecule takes a kind of β turn structure with the d -Phe-Ala residues at the corner of the bend. This turn conformation is primarily formed by the strong intramolecular hydrogen bonds of NH(Gly)—O^δ1 (Asp) and NH(Asp)- O^δ1(Asp) pairs, thus forming a 15-membered ring structure. Judging from the published data concerning the structure-activity relationship, this turn conformation may reflect an important feature related to the neuroexcitatory activity of achatin-I.     

Fatty acid compositions of colostrum,cord blood,maternal blood and major infant formulas in Japan

Lipid profiles in colostrum, cord blood, maternal blood and major infant formulas in Japan were analyzed. In the first part of the study, colostrum obtained from 36 normal delivery women and six kinds of infant formulas provided by three major milk companies were analyzed for their fatty acid composition using capillary gas-lipid chromatography. Although enriched with docosahexaenoic acid (DHA), the percent composition of DHA in the six infant formulas (0.15–0.21%) was significantly lower than that in the colostrum (1.1 ± 0.54). Arachidonic acid (AA) and eicosapentaenoic acid (EPA) were present in the colostrum but not detectable in the infant formulas. It is recommended that although the exact amount of specific fatty acids needed in the infant diet was not completely known, to be as close as possible to natural breast milk, the level of DHA, EPA and AA should be raised in the infant formulas. In the second part of the study, 19 pairs of maternal and cord blood were analyzed for their lipid profile. All samples were from normal vaginal delivery. The measurement of cholesterol, triglycerides, phospholipids and free fatty acids was performed with commercially available enzymatic methods on an automated discrete random access analyzer. Total fatty acid was determined as described in the first part of the study. The results were analyzed with Spearman's rank correlation coefficient. No correlation could be found between maternal and fetal concentrations of cholesterol, triglycerides, phospholipids or total fatty acids. Correlation could be found in non-esterified fatty acids, in palmitic acids, and oleic acid levels. It was concluded that the lipid transport and metabolism in the fetal-placenta unit is complex and further delicate investigation is required.     

Clinical and genetic studies of five fatal cases of Japanese Gaucher disease type 1

Five fatal cases of Japanese patients with type 1 Gaucher disease were studied. The causes of death included hemorrhage secondary to esophageal varices (two cases), respiratory distress (one case), hepatic failure (one case) and postoperative sepsis (one case). All of the patients had previous splenectomies, four patients had bone involvement and hepatic cirrhosis. The identified Gaucher genotypes were 1448C/1213G, 1603T/1603T, 1448C/1390G, ?/? and 1213G/1213G. The prognosis of type 1 Gaucher disease is generally good. We propose that patients with a similar clinical course and genotype to those presented in the present study should receive prompt comprehensive treatment. Patients with the 1213G mutation, pulmonary and liver involvement and a previous splenectomy should be considered as candidates for early vigorous treatment.     

A Trial of Chemotherapy for Lung Cancer in Short-Term Hospitalization

Recently the number of patients with lung cancer who receivechemotherapy has been increasing rapidly. Therefore it has becomedifficult to treat all patients with advanced lung cancer onthe basis of accurate protocol in long-term hos-pitalization.Accordingly we tried to treat patients within one week in eachof a number of chemotherapy protocols (short-term hospitalization)and to follow them in the outpatient department. We were ableto accept 61 admissions of 38 patients for chemotherapy fromJune to December 1985. Thus it was possible to take care ofmore than three times as many patients as could be cared forby long-term hospitalization for chemotherapy. Three patientscould not be discharged within one week and eight had to bereadmitted because of leucopenia, thrombocytepenia, or dehydration.It was considered to be possible to decrease the number of suchpatients by more careful and appropriate hydration and to detectthem by appropriate intervals of examination in the outpatientdepartment. We concluded that short-term hospitalization isone of the methods which can make chemotherapy of lung cancermore effective.     

Electrical Techniques for Stimulation of the Phrenic Nerve to Pace the Diaphragm: Inductive Coupling and Battery Powered Total Implant in Asynchronous and Demand Modes

A review of the electrical design of a rf inductively coupled phrenic nerve stimulator for the diaphragm developed in our laboratories will be discussed. Modifications of the original circuit are based on long-term laboratory and clinical studies. A total implant battery powered stimulator was designed exclusively for animal studies to evaluate the effects of several stimulating parameters on diaphragm fatigue and neuromuscular structure. On the basis of these studies the optimum current level, stimulus frequency, respiratory rate, electrode configuration, and waveform were selected for clinical use to pace the diaphragm. A multiprogrammable dual output stimulator responsive to interrogation has been constructed and used in the experimental laboratory in anticipation of clinical application. There was an insignificant difference between the effect on neural structure or diaphragm function of stimulation with pulse width modulated constant voltage or with amplitude-modulated constant current. Demand pacing: maintenance of normal PACO2 by monitoring ET PACO2 with feedback to the diaphragm pacemaker to adjust the pacing rate has been successful in the experimental animal.     

Malignant Fibrous Histiocytoma Originating in the Left Spermatic Cord with a Review of 14 Cases in the Literature

An 84-yr-old man developed a small-finger-tip sized tumor inthe left inguinal area about five to six years prior to consultationwith the Urology Department. Later, the tumor extended to thescrotum and the suprapubic area. Histological examination ofan en block specimen showed the tumor to be a malignant fibroushistiocytoma of spermatic cord origin. Fourteen cases in theworldwide literature are reviewed, and characteristics of malignantfibrous histiocytoma at this particular site are discussed.     

Increased biosynthesis of thromboxane A2 by diabetic platelets

Abstract. Because ADP has been reported to produce a secondary wave of platelet aggregation in diabetic subjects, and since ADP is known to enhance normal platelet biosynthesis of pro-aggregating thromboxane A₂, we tested whether or not the reported increased sensitivity of diabetic platelets to ADP may also result in increased platelet biosynthesis of thromboxane A₂. To test this hypothesis, ¹⁴C-arachidonic acid (¹⁴C-AA) was incubated in vitro with washed human platelets' in the presence or absence of ADP. These studies included platelets isolated from thirty normal volunteers, twenty-six diabetic subjects with and without known vascular complications, eighteen non-diabetic pregnant females and fourteen pregnancy-induced diabetic females. Data from these studies demonstrated: (i) a significant increase in the capability of diabetic platelets in response to ADP to biosynthesize thromboxane A₂ from arachidonic acid when compared to platelets from normal controls (P < 0.001); (ii) a significant increase in thromboxane A₂ biosynthesis by platelets from pregnancy-induced diabetic subjects over nondiabetic pregnant females (P < 0.001); (iii) a two-fold increase in thromboxane A₂ biosynthesis by platelets from diabetic subjects with vascular complications when compared to those without vascular complications. Although our data also showed approximately a twofold increase in thromboxane A₂ biosynthesis by platelets from diabetic subjects with greater than 10 years of the disease when compared to diabetic subjects with less than 10 years, these latter results were, however, not statistically significant. Results from these studies suggest that a relationship may exist between the markedly increased ADP-induced platelet aggregation in diabetes mellitus and the vascular complications associated with this disease. Whether or not increased capacity of the diabetic platelet to biosynthesize pro-aggregating thromboxane A₂ in response to ADP or other pro-aggregating agents is per se a triggering factor in occlusive vascular diseases reported in diabetic subjects must await further studies.