The Disposition of (R)-α-Methylhistamine,a Histamine H3-Receptor Agonist,in Rats

Abstract— Using a modified HPLC method with a fluorescence spectrophotometer and a weak cation exchanger, it was possible to separate (R)-α-methylhistamine (α-methylhistamine) from histamine in plasma and various tissues. The assay was used to study the disposition and pharmacokinetic analysis of α-methylhistamine after a bolus intravenous administration to rats. After rapid intravenous administration (12·6 mg kg^?1), the plasma concentration declined biexponentially with a half-life of 1·3 min in the elimination phase. The area under the plasma concentration-time curve and total body clearance were 130 μg min mL^?1 and 97 mL min^?1 kg^?1, respectively. After administration, α-methylhistamine was immediately transferred to various tissues. The concentration was high in the kidney, lung, and liver (kidney > lung > liver), but low in the brain. The tissue-to-plasma concentration ratios in peripheral tissues were greater than 1, suggesting that the transfer of α-methylhistamine to peripheral tissues was due to a specialized transport mechanism or possibly to tissue binding. However, the finding that the tissue/plasma ratio in the brain was lower than unity suggests that the transport system in this tissue depends on a concentration gradient, and that α-methylhistamine crosses the blood-brain barrier in rats with difficulty.     

Intussusception Caused by Subserosal Lipoma of the Ileum

Abstract: In this study a case of ileal subserosal lipoma with ileocolic intussusception is reported, together with a review of the literature. The patient, a 37-year-old female, was admitted with melena and abdominal pain. A complete blood cell count revealed microcytic anemia. An ultrasonography and CT scan revealed ileocolic intussusception. On colonoscopy, a tumor was seen at the site of the ileocecal valve. Subsequently, the tumor was retracted mechanically using an endoscope. An ileogram taken after retraction revealed the tumor to have been about 50 cm proximal to the ileocecal valve. In addition to the tumor, 6 cm of the ileum was resected. The tumor was 2.5 cm in diameter; the histological diagnosis was subserosal lipoma of the ileum. This is a rare case of intussusception due to an intestinal lipoma diagnosed by various visual examinations before surgery.     

Influence of left ventricular filling profile during preceding control beats on the occurrence of pulse deficit caused by ventricular premature contractions

This study was designed to investigate whether the left ventricularfilling profile during preceding control beats significantlyaffects the pulse deficit caused by ventricular premature contractions(VPCs). The study group consisted of 18 patients (10 men, eightwomen, 15–85 years old) who underwent electrophysiologicalcatheterization because of sinus bradycardia. Using a temporarypacing lead inserted in the right ventricular apex, isolatedVPCs with various coupling intervals were produced by electricalstimulation of the right ventricle. During the production ofthe VPCs, the mitral filling flow velocity using pulsed waveDoppler echocardiography, the femoral arterial pressure curveand the electrocardiogram were simultaneously recorded. Theright ventricle was siimulated 800, 750, 700, 650, 600, 550,500, 450 and 400 ms after the triggered control beat QRS complex.Pulse pressures during VPCs gradually decreased in relationto the shortening of the extra-systolic beat coupling interval.The longest coupling interval for each subject, which causedcomplete abolition of the pressure pulse during the VPC, wasdefined as the pulse deficit coupling interval. The early tolate diastolic velocity–time integral ratio (E_i/A_i ratio)of the mitral filling flow velocity during the control beatswhich precede the VPC was obtained as an index expressing theleft ventricular filling profile. The E_i/A_i ratio of the mitralfilling flow velocity ranged from 0.7 to 4.5 (1.8 ± 1.0).The pulse deficit coupling interval ranged from 440 to 640 ms(510 ± 60 ms). A significant negative correlation wasobserved between the E_i/A_i ratio and the pulse deficit couplinginterval (r = –0.69, P<0.01). A significant positivecorrelation was also observed between the age and the pulsedeficit coupling interval (r = 0.63, P<0.01). The findingsare consistent with the concept that pulse deficit by VPCs mayeasily occur in patients with reduced left ventricular fillingduring the early diastole.     

Giant microcystic adnexal carcinoma of the scalp

Microcystic adnexal carcinoma (MAC) is an uncommon, locally aggressive tumor. It typically involves the upper lip of middle‐aged adults, and in rare instances the scalp. We report a Japanese woman with a giant MAC on the scalp. Physical examination revealed a 110 mm × 120 mm induration on her parietal region. Microscopically, the tumor showed both pilar and sweat gland differentiation. Resection included the cranium; for reconstruction we used a titan mesh allograft and covered it with a free latissimus dorsi muscle flap and a mesh skin graft. Ours is the first case of a MAC measuring more than 100 cm² arising on the scalp of an individual in the third decade of life.     

Optimal Programming of the Atrioventricular Delay Using the Phonocardiogram

Purpose: To predict the optimal atrioventricular (AV) delay using the phonocardiogram (PCG).
Methods: We studied 12 recipients of cardiac resynchronization therapy (CRT) system and eight recipients of dual-chamber pacemakers implanted for AV block with normal left ventricular (LV) function. The amplitude of the first heart sound (S1) was recorded by PCG and the LV outflow tract (OT) time-velocity integral (TVI) was measured by pulsed Doppler echocardiography. The AV delay was prolonged in 20-ms increments, from 60 ms to 240 ms. Ishikawa's method was used for the echocardiographic optimization of the AV delay. The relation between S1 amplitude and the AV delay was analyzed.
Results: The correlation between the amplitude of S1 and the length of AV delay showed an S-shaped curve. The AV delay at the inflection point of each patient's S-shaped curve (161.2 ± 19.5 ms) was positively correlated with the optimal AV delay determined by echocardiography (148.3 ± 16.9 ms, r = 0.83, P < 0.001). In addition, there was a positive correlation between the AV delay at the maximal TVI of LVOT (150.8 ± 22.7 ms) and the AV delay at the inflection point of the S-shaped curve (159.5 ± 24.9 ms, r = 0.87, P < 0.001). In two CRT system recipients, an optimal AV delay could not be found by echocardiography; however, an optimal AV delay could be determined by PCG.
Conclusions: A high correlation was observed between the optimal AV delay determined by phonocardiography versus echocardiography.     

Polyamine‐promoted autoactivation of plasma hyaluronan‐binding protein

See also Kanse SM, Etscheid M. Factor VII activating protease (FSAP): caught in the cross‐fire between polycations and polyanions. This issue, pp 556–8. Summary. Background: Plasma hyaluronan‐binding protein (PHBP), a protease implicated in extracellular proteolysis, consists of multiple domains: an N‐terminal region (NTR), three epidermal growth factor (EGF)‐like domains, a kringle domain, and a protease domain. PHBP circulates as a single‐chain proenzyme (pro‐PHBP), which is converted to an active, two‐chain form through autoproteolysis. Objective: To understand the mechanism of autoactivation. Here, we report that polyamine induces the formation of pro‐PHBP autoactivation complex, in which an intermolecular interaction between NTR and the third EGF‐like domain (E3) plays a role. Methods: Using a series of pro‐PHBP mutants that partially lack functional domains, polyamine‐induced pro‐PHBP autoactivation was investigated in terms of enzyme activity, protein interaction, and inhibition by carminic acid, an anthraquinone compound identified in this study. Results: Polyamine enhanced intermolecular binding of pro‐PHBP, but not of mutant pro‐PHBP that partially lacked NTR (ΔN). Carminic acid inhibited intermolecular pro‐PHBP binding and specifically abolished polyamine‐induced autoactivation. NTR bound to pro‐PHBP and ΔN, but its binding was minimal to a mutant that lacked E3. The NTR‐ΔN binding was inhibited by a combination of polyamine and carminic acid, but each compound alone was ineffective. Conclusions: We infer from the data that (i) polyamine modulates intramolecular NTR‐E3 interaction to allow intermolecular binding between NTR and E3 in another pro‐PHBP molecule to form an autoactivation complex, and (ii) carminic acid inhibits polyamine‐modulated intermolecular NTR‐E3 binding. Polyamine concentrations are higher in cells and tissues with inflammation and malignancy. Polyamine leakage from legions through cell death or tissue injury may account for physiologically relevant pro‐PHBP activation.     

Promoting the effects of intravesical instillation of saline on bladder lesion development in rats pre-treated with BBN

BACKGROUND: At present, immunotherapeutic agents such as bacillus Calmette-Guerin (BCG) and anti-tumor chemotherapeutic agents in saline are used intravesically in patients with bladder carcinoma. However, of greater significance is the possibility that the saline vehicle may itself promote carcinoma development in the bladder. METHODS: The potential promoting effects of intravesical instillation of saline were assessed in female F344 rats. The animals were divided into 3 groups, all of which received 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for the first 10 weeks. They were then maintained without further treatment (group 1) or received intravesical instillations of 0.3 mL of saline or distilled water once a week for 6 weeks, 15 weeks after the end of the BBN treatment (groups 2 and 3). At 32 weeks, all the animals were killed and examined immunohistochemically with proliferating cell nuclear antigen (PCNA) antibody, as well as by routine histopathologic examination. RESULTS: Both the incidence and the number of bladder carcinomas were higher in the animals that received instillations of saline than in those who did not receive the instillations. Significant increases in tumor size were also noted for the saline-treated groups, although this was not linked with the PCNA labeling index. CONCLUSIONS: The results indicate that saline is a promoter of urinary bladder carcinogenesis either because of the catheterization or the fluid itself.