Negative inotropic effect of 3,6-dimethamidodibenzopyriodonium citrate (I-65) on guinea pig papillary muscles

The effects of 3,6-dimethamidodibenzopyriodonium citrate (I-65) on the contractile response of electrically paced guinea pig papillary muscles in vitro were studied. I-65 (0.1-300 mumol/L) decreased the contractile force and inhibited isoprenaline-induced restoration of the contractile response in papillary muscles rendered inexcitable by KCl 22 mmol/L. Both effects were concentration-dependent, and the IC50 were 36.0 and 7.3 mumol/L, respectively. I-65 antagonized the positive inotropic effects of Iso and CaCl2 in a non-competitive manner. Like verapamil, I-65 had a frequency-dependent negative inotropic effect, and delayed the recovery of post-rest potentiation. It is concluded that the negative inotropic effect of I-65 results not only from the reduction of Ca2+-influx through the sarcolemmal membrane, but also from the inhibition of Ca2+ translocation in the sarcoplasmic reticulum.     

Representativity of endomyocardial biopsies: a theoretical approach based on quantitative light microscopy

To create a model for studying the regional variation in the histologic structure of left ventricular myocardium and the representativity of samples from endomyocardium in predicting the state of myocardium as a whole, 12 human hearts (3 normal and 9 pathological) were investigated with histoquantitative methods. Ten small endomyocardial areas representing biopsy sites (mean area on section 0.94 mm2) were delineated from each heart. The volume fractions of myocardial fibers (VVMY), interstitial space (VVINT) and connective tissue (VVCT) were determined with a point counting method on these areas. Also the mean fiber diameter was measured. The results were compared with the results from three full thickness samples (mean area 3 cm2) from each heart. The values for fiber diameter estimates were almost identical in endomyocardial samples and full thickness samples. On the other hand, VVCT was significantly higher and VVMY lower in endomyocardial samples. The coefficient of variation (10 endomyocardial areas) was 8.3% for fiber diameter, 17.8% for VVMY and 77.5% for VVCT. When estimates of the regional variation within the heart area are available, it is possible to create a model for the prediction of the number of endomyocardial biopsies needed to reach a given accuracy and probability of measurements. The representativity and clinical value of endomyocardial biopsies are discussed on the basis of this statistical approach.     

ACTIVIT OF HUMAN PLACENTAL GAMMA GLOBULININ BLOCKING IMMUNE FUNCTIONS IN VITRO AND IN ABROGATING THE XENOGENEIC, LOCAL GRAFT-VERSUS-HOST-REEACTEON

In order to understand the mechanism of immunosuppression caused by infusion of placental gamma globulin (PGG) in patients with renal allografts, rheumatoid arthritis, and graft – versus –host disease (GCHD) following bone marrow transplantation (BMT) ,we have examined the effect of PGG in vitro and in a model of the xenogeneic , local graft –ver- sus – host reaction (LGVHR) .PGG inhibited lymphocyte proliferation in mixed lymphocyte cultures (MLC) (P<0.005) and depressed interleukin -2 (IL-2) levels in such cultures at 72 hours (P<0.01) . In contrast phytohemagglutinin (PHA) –and pokeweed mitogen (PWM) –induced T and B lymphocyte blastogenesis was not affected by such PGG treatment .PGG treatment .PGG neither decreased the [3H] TdR pulse incorporation in unstimulated lymphocytes nor affected cell viability .Cell cycle analysis by flow cytometry showed that PGG reduced the percentage of cells in S and G2, M phases during the MLC, but did not alter cell cycling during PWM-stimulated proliferation . An immunosuppressive effect of PGG on the LGCHR was tested in a model of intracutaneous transplantation of PGG –treat human lymphocytes into cyclophosphamide – immunosuppressed rats. Lymphoprep – separated human tonsillar lymphocytes were incubated with RPMI-1640 buffer containing：（1）PGG,4mg/ml,(2) human plasma albumin,4mg/ml,(3)mitomycin-C,25ug/ml, or (4) no additive. Cell of each preparation (3x107cells in 0.1ml) were injected intracutaneously into cyclophosphamide-treated male rats at separate abdominal locations. A fifth site received only the buffer solution. Five days after injection of cells ,each rat received [125 I]IUdR (10uCi) intraperitoneally and was killed after 5 hours. For each site of injection, the diameters of induration were measured and 125 I was counted . There was no difference between buffer – treated and a ibumin – treated groups either in the diameter of the area of induration (t=0.66;P>0.5)or in radioactive counts(t=0.22;P>0.05).In the PGG –treated group, the induration and radioactivity measurements were significantly less than in control groups (t=3.72 and P<0.1;t=2.62 and P<0.02,respectively ) Cytophilic antibodies in PGG were thought to inhibit an early phase of T cell activation, and not to be cytotoxicity .In the LGVHR, the immune response might be abrogated either by immuno- regulatory suppression of T cell function or by toxicity to the infused lymphoid cells. For some clinical purposes, immuno- modulating, human antibodies might be preferred to murine, monoclonal antibodies.     

Induction of gastric tumor and intestinal metaplasia in rats exposed to localized X-irradiation of the gastric region

The induction of gastric tumor and intestinal metaplasia was examined in 8-week-old male JCL/SD rats exposed to localized X-irradiation of the gastric region. The animals were each given two 20 Gy fractions of X-rays, with a one-week interval between fractions (total, 40 Gy). Nine atypical hyperplasias (20%) and 13 adenocarcinomas (28%) in the pyloric mucosa of the glandular stomach were found in 46 animals with X-irradiation. The incidence of intestinal metaplasia was 93% in the pyloric mucosa, 50% in the fundic mucosa and 96% in both the pyloric and fundic mucosa. Type B metaplasia (intestinal metaplasia without Paneth cells) was most common and type C (intestinal metaplasia with Paneth cells) was less frequent. No gastric tumor or intestinal metaplasia appeared in non-irradiated control rats. This study shows that local X-irradiation of the gastric region induced both gastric tumor and intestinal metaplasia independently.     

Paraneoplastic dermatopolymyositis

In a retrospective study covering 11 years, 59 adult cases of dermatomyositis or polymyositis were reviewed. The disease was of paraneoplastic origin in 9 cases (15,25 p. 100), the same proportion as that found in the literature (14,6 p.100). The striking female predominance (8/9 cases) and the patients' mean age (61.11 years) were higher than those noted in non-paraneoplastic dermato- and polymyositis in adults (female predominance 34/50, mean age 52.9 years). Clinically, out of 9 patients 7 had dermatomyositis and 2 had polymyositis. The disease was discovered at the same time as the neoplasia in 7 of the 9 cases. Muscle histology showed that in contrast with non-paraneoplastic cases of dermatomyositis-polymyositis those of paraneoplastic origin had moderate lesions without fibrosis.     

Antiherpes activity of chemically synthesized lipid A-subunit analogue GLA-60 in immunosuppressed mice

Intraperitoneal administration of 10 micrograms GLA-60, a chemically synthesized lipid A analogue, to mice one day after treatment with 200 mg/kg of cyclophosphamide (CY) significantly increased the number of macrophages, lymphocytes and polymorphonuclear leukocytes (PMNs) in the peritoneal cavity. The intrinsic antiviral activity of macrophages against herpes simplex virus type 1 (HSV-1) as well as natural killer (NK) activity against YAC-1 target cells was stimulated by administration of GLA-60 to CY-immunosuppressed mice. When the mice were administered GLA-60 prior to HSV-1 infection, virus growth was inhibited and the mortality rate of infected mice was reduced. Thus, GLA-60 is a potent immunomodulator achieving its antiviral action through enhancement of nonspecific host defense mechanisms. Combined treatment of GLA-60 with the antiviral agent acyclovir (ACV) resulted in greater protection against HSV-1 in the CY-immunosuppressed mice than did single treatment with either GLA-60 or ACV.     

Metabolic and morphological alterations of brown adipose tissue after sympathetic denervation in rats

Effects of sympathetic denervation on biochemical and morphological changes of brown adipose tissue (BAT) were studied in rats after severing 5 intercostal nerve bundles that enter the unilateral interscapular BAT, the contralateral BAT being used as the control. Four weeks after denervation, there was no appreciable change in BAT weight or its DNA and protein contents, whereas the triglyceride content was increased significantly. However, the rate of fatty acid synthesis was decreased to about half the rate in controls. The denervated BAT was much paler than controls and contained lots of adipocytes filled with large lipid droplets, some of which were unilocular. The results are discussed with reference to changes in BAT seen after bilateral lesions of the ventromedial hypothalamus.     

Clinical study on cefixime granules in the field of pediatrics

The absorption and excretion and clinical effectiveness of cefixime (CFIX) granules, a new oral cephalosporin, were studied with pediatric patients with tonsillitis and urinary tract infection (UTI). Peak serum concentrations in 3 children given orally a single dose of 3 mg/kg on fasting were 0.545 micrograms/ml at 2 hours in 1 patient, and 1.56 and 1.26 micrograms/ml at 4 hours in the other 2. The half-lives in the 3 patients were 3.21-3.42 hours, with an average of 3.29 hours. The urinary concentration during the first 6 hours was 36.5 micrograms/ml in 1 patient showing the low serum level, and the first 6-hour urinary recovery rate was 7.3%. In the other 2 patients, urinary concentrations and recovery rates up to 6 hours were 87 and 62 micrograms/ml, and 17.0 and 15.1%, respectively. The second 6-hour urinary concentrations and recovery rates were 35.5 and 20.8 micrograms/ml, and 12.7 and 8.8%, respectively. The urinary recovery rates up to 12 hours were 29.7 and 23.9%, respectively. CFIX was given orally to 19 children with 20 diseases in daily doses of 6.4-12.9 mg/kg in 2 or 3 divided portions for 3 to 12 days. Clinical evaluations were made on 18 diseases. Clinical effects of CFIX were excellent in 4, good in 7 and poor in 1 of the 12 patients with tonsillitis, and excellent in 5 and good in 1 of the 6 patients with UTI. The overall clinical effectiveness rate was 94.4%. No side effects were observed in any of the 19 patients. Hematological tests, showed slight elevation of blood platelet counts in 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)