Electrophysiological and Anatomical Substrates for Late Potential Recorded by Signal Averaging in Seven-Day-Old Myocardial Infarction in Dogs

A filtered QRS (fQRS) was recorded by signal averaging in 7-day-old myocardial infarction (MI) in dogs to detect late potential (LP). The criteria for the LP included a duration of fQRS (D) greater than or equal to 60 msec and a voltage in the last 15 msec (V15) less than or equal to 10 microV. These parameters were determined from the control data from 15 dogs without infarction (D: 45 to 60 msec and V15: 12.0 to 83.6 microV). On the seventh day of infarction, the D had increased from 53.5 +/- 4.7 to 62.2 +/- 9.6 msec (P less than 0.05) and the V15 decreased from 38.6 +/- 19.5 to 18.4 +/- 16.0 microV (P less than 0.01). Of 23 dogs, 14 met the LP criteria (group A) and 9 did not (group B). Sustained ventricular tachycardia (SVT) was induced in 12 group A dogs and in none of the group B dogs. The delayed epicardial activation (DEA) was recorded after the end of QRS at 5.1 +/- 4.7 sites in group A dogs and 1.3 +/- 1.8 sites in group B dogs (P less than 0.05). The maximum value of epicardial activation time was more prolonged in group A than in group B (70.0 +/- 28.3 vs 44.4 +/- 9.8 msec, P less than 0.01). The area of MI was more extensive in dogs with DEA than those without (24.9 +/- 5.8% vs 10.3 +/- 9.0% of the total left ventricular weight, P less than 0.01). In 72 of 90 sites with DEA, the thickness of the surviving epicardial muscle was less than or equal to 1 mm. The sensitivity and specificity of the criteria for LP in detecting DEA were 71.4% and 55.6%, and 100% and 81.8% for predicting inducibility of SVT. It was thus concluded that LP, reflected the DEA, was identified from infarct areas of slow conduction within a reentry circuit of SVT.     

Peracylated β-Cyclodextrins as Novel Sustained-release Carriers for a Water-soluble Drug,Molsidomine

Abstract— Peracylated β-cyclodextrins with different alkyl chains (acetyl-octanoyl) were prepared by acylating all hydroxyl groups of β-cyclodextrin (β-CyD), and their physical properties were evaluated. These hydrophobic β-CyDs decreased the release rate of molsidomine, a peripheral vasodilator, in proportion to the lengthening of alkyl chain and suppressed a peak plasma level of molsidomine following oral administration of peracylated β-CyD complexes to dogs. Among the peracylated β-CyDs tested, perbutanoyl-β-CyD maintained sufficient plasma drug levels for a long period of time, while other peracylated β-CyDs having shorter or longer chains were inappropriate to control the in-vivo release behaviour of molsidomine. The prominent retarding effect of perbutanoyl-β-CyD was ascribable to the appropriate mucoadhesive property and hydrophobicity, compared with other peracylated β-CyDs. The present results suggest that perbutanoyl-β-CyD is particularly useful in modifying the release rate of water-soluble drugs as a novel slow-release carrier.     

In-vivo and in-vitro evaluations of a modified-release oral dosage form of nifedipine by hybridization of hydroxypropyl-β-cyclodextrin and hydroxypropylcelluloses in dogs

Abstract— To maintain a suitable blood level of nifedipine for a long period of time, double-layer tablets consisting of 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) and 3% nonionic surfactant (HCO-60) as a fast-release portion and hydroxypropylcelluloses (HPCs) with different viscosity grades (low, medium and high) as a slow-release portion were prepared, and their in-vitro and in-vivo release behaviours were investigated. Among the seven formulations, the tablet having the mean dissolution time of 0·8–1·3 h gave prolonged plasma nifedipine levels without decrease of AUC after oral administration to dogs. Consequently, the double-layer tablet consisting of HP-β-CyD with 3% HCO-60/(HPC-low: HPC-medium) in a weight ratio 1/(1·5:1·5) was selected as an appropriate modified-release formulation because it elicited almost comparable retarding effects with superior oral bioavailability compared with those of a commercially available slow-release nifedipine product.     

Aluminium β-Cyclodextrin Sulphate as a Stabilizer and Sustained-release Carrier for Basic Fibroblast Growth Factor

Abstract— The water-insoluble aluminium salt of β-cyclodextrin sulphate (Al · β-CyD-Sul) was used as a stabilizer and sustained-release carrier for recombinant human basic fibroblast growth factor (bFGF). An adsorbate of bFGF with Al · β-CyD-Sul was prepared by incubating the protein with a suspension of Al · β-CyD-Sul in water. The mitogenic activity of bFGF released from the adsorbate, as indicated by the proliferation of kidney cells of baby hamster (BHK-21), was almost comparable with that of the intact bFGF. Al-β-CyD-Sul significantly protected bFGF from proteolytic degradation by pepsin and α-chymotrypsin, compared with the water-soluble sodium salt. The in-vitro release of bFGF from the adsorbate was sustained in proportion to a rise in the ratio of Al · β-CyD-Sul to the protein in the adsorbate. Of the bFGF preparations evaluated, the adsorbate of bFGF with Al ·β-CyD-Sul, when given subcutaneously to the rat, showed the most prominent increase in the formation of granulation tissues, due to the stabilization and slow-release of the mitogen. The limited data presented here suggest that the adsorbate of bFGF with Al · β-CyD-Sul has a potent therapeutic efficacy for wound healing, and may be applicable to oral protein formulations for the treatment of intestinal mucosal erosions.     

RHINOPHYMA IN JAPAN

Background. Rhinophyma is an end stage of acne rosacea. It results in a large nose due to a proliferation of sebaceous glands and fibrous tissue. Many cases of rhinophyma have been reported in the Western world; however, in Japan, rhinophyma has been an uncommon disease. Methods. We present two patients associated with rhinophyma who were treated by cross-shaped full-thickness excision followed by direct closure and compare the rhinophyma in Japan with that in the West. Results. To date, only 20 rhinophyma cases including our 2 cases have been reported in Japan. Epidemiologic factors of rhinophyma between the West and Japan do not differ except for location, malignancy and surgical treatment. Conclusions. In Japan, almost all cases are located on the lower half of the nose, treated by full-thickness excision followed by application of either skin grafts or direct closure. None have been malignant.     

The expression of mRNA for tumour necrosis factor-α increases in the obstructed kidney of rats soon after unilateral ureteral ligation

Summary: Cytokines, including transforming growth factor (TGF)-β1, contribute to the tubulointerstitial fibrosis of ureteral obstruction. Tumour necrosis factor (TNF)-α, a proinflammatory cytokine produced by multiple cells including macrophages and resident renal cells, has a role in inflammatory cell recruitment in glomerular injury. We measured TNF-α mRNA in the renal cortex of rats at different times after the onset of unilateral ureteral obstruction (UUO) and determined whether angiotensin II (AngII) inhibition or total body irradiation affects the mRNA levels of TNF-α. Rats were killed at 1, 2, 4, 24, 72 and 120h after UUO. Levels of TNF-α mRNA increased significantly in the obstructed kidney at 1h (X 2), 2h (X 2.7), 4h (X 3.6), 24h (X 2.7), 72h (X 1.8) and 120h (X 2.8) after ureteral ligation when compared to the contralateral kidney of the same animals or to control (normal) kidneys. Tumour necrosis factor-α mRNA increased in renal cortical tubules but not in glomeruli. Treatment with enalapril, an angiotensin-converting enzyme (ACE) inhibitor, before and after UUO decreased TNF-α mRNA levels in the obstructed kidney by about 40% at 4h after the onset of UUO, but at 120h there was no difference in TNF-α levels in the obstructed kidney of treated and untreated animals. Total body irradiation, which depletes macrophages in the obstructed kidney, did not prevent the upregulation of TNF-α mRNA expression at 4 h after UUO. Thus, TNF-α may have a role in initiating tubulointerstitial injury in the obstructed kidney. Leucocytes infiltrating the renal interstitium of the obstructed kidney do not appear to contribute to the increased mRNA expression of TNF-α. Angiotensin II may contribute, at least in part, to the early increased expression of TNF-α mRNA in the obstructed kidney.     

Factors determining prenatal HIV testing for prevention of mother to child transmission in Dar Es Salaam, Tanzania

BACKGROUND: The objectives of the study were (i) to evaluate the Prevention of Mother to Child Transmission (PMTCT) services in Temeke district, Tanzania and (ii) to identify factors for non-acceptance of HIV testing among pregnant mothers in the area. METHODS: A structured questionnaire was used in face-to-face interviews at five health centers in the district. Univariate and multiple logistic regression analyses were used to assess the association of the refusal of human immunodeficiency virus (HIV) testing with risk factors. RESULTS: Two hundred and seventy-three (68.1%) of the participants had already had HIV testing, while 128 (31.9%) had not. Participants' general knowledge of HIV was high, but specific knowledge of mother to child transmission (MTCT) was relatively low. In the multiple logistic regression analysis, frequencies of antenatal clinic visits, awareness of MTCT and intensive family support were significantly and inversely associated with the refusal of HIV testing. CONCLUSIONS: Frequency of antenatal care visits, spreading information on HIV/acquired immune deficiency syndrome especially MTCT, and husbands' intensive support are significant factors for increase of HIV test acceptance among pregnant women in the study area.     

In-vivo and In-vitro Correlation for Delayed-release Behaviour of a Molsidomine/O-carboxymethyl-O-ethyl-β-cyclodextrin Complex in Gastric Acidity-controlled Dogs

The in-vivo absorption behaviour of molsidomine from the delayed-release tablets of an O-carboxy-methyl-O-ethyl-β-cyclodextrin complex was investigated using gastric acidity-controlled dogs under fasted and non-fasted conditions. The in-vitro release profiles were generated by changing the pH of the dissolution medium at different rotation paddle speeds. The absorptivity of molsidomine in the high acidity dog was correlated with the pH-changed release profile (pH 1·2 to 7·0 after 2 h), whereas that in the low acidity dog was correlated with the release profile at a constant pH of 7·0. The absorption in fasted dogs was well correlated with the in-vitro release at the low-rotation paddle speed (< 5 rev min^?1), whereas that in the non-fasted dogs was correlated with that of high rotation (100 rev min^?1). The present results suggested that the in-vivo delayed-release behaviour of the complex is predictable from the in-vitro release profiles generated using pH-variable dissolution testing apparatus at different rotation speeds of the paddle.