A method for evaluating antianginal drugs in experimental animals: assessment of myocardial ischemia by myocardial pH

This paper describes a method by which antianginal drugs can be evaluated in the dog heart in situ. Myocardial pH was measured continuously by a micro glass pH electrode inserted in the left ventricular endocardial layers of the dog anesthetized with pentobarbital. Occlusion of the left anterior descending coronary artery (LAD) decreased myocardial pH, and release of the LAD restored the pH. The myocardial acidosis induced by ischemia was metabolic in nature and accompanied by a decrease in the levels of adenosine triphosphate and creatine phosphate and an increase in the levels of lactate in the myocardium. Drugs were injected intravenously 30 min after incomplete (partial) occlusion ot the LAD, lasting until 60 min after drug injection. Propranolol, atenolol, and sotalol markedly attenuated the myocardial pH that had been decreased by LAD occlusion. Nitroglycerin, diltiazem, and nicorandil also attenuated the pH, but these drugs were less active in attenuating myocardial acidosis. Dipyridamole, nifedipine, and beta-2 adrenoceptor antagonists were least active in this regard. It is concluded that myocardial pH can be used as an indicator of myocardial regional ischemia and utilized for evaluation of antianginal drugs.     

Expression profile of chemokines and chemokine receptors in epithelial cell layers of oral lichen planus

BACKGROUND: To understand the immunopathological features of oral lichen planus (OLP), we analyzed the expression of chemokines in the epithelial cell layers. Methods: Epithelia from OLP or healthy gingiva were collected by laser microdissection. The chemokine and chemokine receptor expressions in the epithelia were analyzed by DNA microarray. RESULTS: High levels of MIP-3alpha/LARC/CCL20 and its receptor CCR6 were expressed in the lesional epithelia. Furthermore, DC-CK1/CCL18, ELC/CCL19, SDF-1/CXCL12 and CXCR4 expressions were also increased. Immunohistologial analysis showed that high numbers of Langerhans cells (LCs) were present in the epithelia of OLP. Lesional epithelia also expressed high levels of the ligands specific for CXCR3 (e.g. MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11) and CCR5 (e.g. RANTES/CCL5). CONCLUSIONS: Infiltration of LCs is orchestrated by CCR6. Further, LCs residing in the lesional epithelia may be a mature phenotype. Moreover, infiltration of T cells in OLP could be mediated by signaling pathways through CXCR3 and CCR5.     

Insulinoma: Selective arterial calcium injection performed to confirm localization and complete resection

A case of insulinoma is reported in a patient in whom selective arterial calcium injection (SACI) tests were performed both to confirm tumor localization before surgery and to confirm complete tumor removal during surgery. An 18-year-old woman with hypoglycemic episodes was diagnosed with an insulinoma in the pancreatic body demonstrated by celiac arteriography. In a preoperative SACI test, calcium was injected into the splenic artery (SpA), gastroduodenal artery (GDA), and superior mesenteric artery (SMA). Serum immunoreactive insulin (IRI) and proinsulin levels were measured in hepatic venous samples. IRI was markedly increased after the injection of calcium into the GDA and SMA, while there was no response in IRI levels when calcium was injected into the SpA. Therefore, no occult insulinoma was revealed in the distal area fed by the SpA, although the presence of insulinoma was uncertain in the proximal pancreas. In the intraoperative SACI test, calcium was injected into the celiac artery. Insulin (determined by enzyme immunoassay) and proinsulin levels were measured in portal venous samples before and after resection of the tumor. After resection, these levels decreased in response to the calcium stimuli, confirming complete removal of the insulinoma. The SACI test was helpful to localize the insulinoma and was useful to confirm the complete removal of the tumor.     

Dynamic MRI of the gallbladder lesions: Differentiation of benign from malignant

Forty-nine pathologically proven gallbladder lesions were evaluated in 45 patients using dynamic MRI with a spoiled gradient pulse sequence (SPGR), to access the ability of this technique to differentiate benign from malignant gallbladder lesions. The studies were reviewed retrospectively. Signal intensity of the lesions were measured. Twenty-one malignant and 28 benign lesions were classified into three categories: polypoid, diffuse wall thickening, and exophytic. Early and delayed enhancement patterns were evaluated. For the polypoid masses, malignant lesions (n = 9) demonstrated early and prolonged enhancements, whereas benign lesions (n = 14) had early enhancement with subsequent washout (P < .05). For diffuse gallbladder wall thickening, malignant lesions (n = 6) demonstrated early and prolonged enhancement and benign lesions (n = 14) showed relatively slow, prolonged enhancement (P < .05). The exophytic masses (n = 6) all were malignant and demonstrated early and prolonged enhancement. Dynamic MRI can help differentiate benign from malignant gallbladder lesions.     

Development of a new wound dressing with antimicrobial delivery capability

A bilaminar wound dressing composed of an outer membrane and an inner three-dimensional matrix of a fabric or a sponge may be considered to constitute an ideal structure that promotes wound healing: the outer membrane prevents body fluid loss, controls water evaporation, and protects the wound surface from bacterial invasion, and the inner matrix encourages adherence by tissue growth into the matrix. Using this concept, we developed a biosynthetic wound dressing with a drug delivery capability. This medicated wound dressing is composed of a spongy sheet of a chitosane derivative and collagen mixture that is laminated to an antimicrobial-impregnated polyurethane membrane. In this study, a gentamycin sulfate-impregnated wound dressing was prepared and evaluated. The antimicrobial efficacy of this wound dressing was examined on an agar plate seeded with Pseudomonas aeruginosa. Also, the cytotoxicity of an antimicrobial released from this wound dressing was examined in an in vitro system with cultured skin substitutes. Both in vitro tests have shown that this wound dressing is capable of suppressing bacterial growth and minimizing cellular damage. In addition, in the treatment of wounds inflicted on rats and rabbits, this wound dressing was shown to be efficacious in covering full-thickness and split-thickness skin defects. Finally, the efficacy of this wound dressing was evaluated in a nonrandomized open-label study of 31 clinical cases. In 31 cases treated with this wound dressing, good or excellent wound healing was achieved.     

Effect of lidocaine on the myocardial acidosis induced by coronary artery occlusion in dogs

The effect of lidocaine on ischemic myocardial acidosis was investigated in the dog heart, in which the left anterior descending coronary artery was occluded to reduce to about one-third (partial occlusion). Myocardial pH (MpH) was measured by means of a micro glass pH electrode. MpH before partial occlusion was 7.52 to 7.66. Partial occlusion decreased the left anterior descending coronary artery flow by 49 to 68%, MpH by 0.58 to 0.76 and myocardial contractile force by 26 to 43%, and increased ST segment (surface electrocardiogram) by 3.2 to 11.7 mV. Lidocaine (injected i.v. 30 min after partial occlusion) decreased heart rate, blood pressure and myocardial contractile force, and attenuated the decrease in MpH during ischemia. Lidocaine in doses of 2, 5 and 10 mg/kg restored the myocardial [H+], that had been increased by partial occlusion, by 23, 38 and 50%, respectively. Even in the paced heart, lidocaine (10 mg/kg) attenuated the myocardial acidosis, although the degree of attenuation was smaller (36%). Partial occlusion elevated the ST segment even in the presence of 5 or 10 mg/kg of lidocaine. In the nonischemic heart, however, lidocaine (2, 5 or 10 mg/kg) did not change in MpH. It is concluded that lidocaine attenuates the myocardial acidosis during ischemia, and the primarily important mechanism of pH attenuation is not a decrease in heart rate.     

Differential expression of human beta-defensin 2 in keratinized and non-keratinized oral epithelial lesions; immunohistochemistry and in situ hybridization

Human beta-defensin(hBD)-2, an antimicrobial peptide, is produced by various epithelial cells. Because hBD-2 expression in the oral epithelium has not been assessed, we investigated its localization in normal oral epithelium and epithelial lesions. hBD-2 expression was studied using immunohistochemistry and in situ hybridization on formalin-fixed, paraffin-embedded tissue sections from 30 cases of squamous cell carcinoma and 6 cases of leukoplakia. Immunostaining for hBD-2 was more intense in hyperkeratinized than in ortho- or non-keratinized epithelium. In contrast, signals for hBD-2 mRNA were frequently stronger in non-keratinized epithelium than in hyper- or ortho-keratinized epithelium. The results suggest that keratinization in oral epithelium plays an important role in the biological function of hBD-2 both at the mRNA level and in the retention of the peptide in the epithelium.     

Seasonal variation in sweating responses of older and younger men

Eight older (60–65 years) and six younger (20–25 years) men were exposed to a standard heat stress for 60 min in summer, autumn, winter, and spring. The test consisted of placing the lower legs and feet in a 42°C water bath while sitting in constant environmental conditions (30°C and 45% relative humidity). The increase of rectal temperature (T _re) was significantly greater (P < 0.05) in autumn, winter, and spring than in summer for the older group, but significantly greater only in winter than in summer for the younger group (P < 0.05). The T _re was greater for the older group in all seasons, but of significance only in autumn and spring (P < 0.01). There were no significant season-related differences for metabolic heat production (m) and mean skin temperature ( _sk) during the heat test in the respective groups, although the m and _sk were lower for the older group in all seasons (P < 0.01). In the older group total body sweating rate (m_sw) divided by T _re (total m_sw/T _re) decreased from summer to winter (P < 0.02) and did not differ between winter and spring, whereas total m_sw/T _re in the younger group increased in spring after decreasing from autumn to winter (P < 0.03). The variations of the value, local sweating rate on the back and thigh divided by T _re (back m_sw/T _re and thigh m_sw/T _re), were similar to those of the total m_sw/T _re in each group, except for back m_sw/T _re in the younger group, which did not increase from winter to spring. The total m_sw/T _re, back m_sw/T _re and thigh m_sw/T _re were significantly less for the older group in summer, autumn and spring (P < 0.05). The range of seasonal variations was significantly less for the older group (P < 0.001). The results indicated that, compared with younger men in older men, the enhancement of sweating function toward summer occurred later and its reduction toward winter occurred earlier despite a smaller range of seasonal variation and that older men had a somewhat lesser capability to maintainT _re when challenged by heat stress in all seasons.     

Blepharophimosis sequence and de novo balanced autosomal translocation [46, XY,t(3;4)(q23;p15.2)]: Possible assignment of the trait to 3q23

We report on a boy with the blepharophimosis sequence and de novo, apparently balanced reciprocal translocation between 3q23 and 4p15.2 [46, XY,t(3;4)(q23;p15.2)de novo]. Possible assignment of this autosomal dominant disorder is discussed. A 3q23 band is a more preferable gene locus of the blepharophi mosis sequence, based on the comparison of clinical manifestations between 4p- and 3q-syndromes.