CHOLINERGIC NEUROMODULATION BY ATP, ADENOSINE AND ITS N6-SUBSTITUTED ANALOGUES IN GUINEA-PIG ILEUM

The effects of ATP, adenosine and N6-substituted adenosines, adenosine receptor agonists, on the twitch contraction of guinea-pig ileum evoked by transmural stimulation were evaluated. Adenosine and ATP produced an immediate and concentration dependent inhibition of the twitch, IC50 being 1.1 X 10(-5) mol/l and 1.2 X 10(-5) mol/l, respectively. N6-l-phenylisopropyl adenosine (L-PIA), N6-cyclohexyl adenosine (CHA) and N6-allyl adenosine also induced inhibitions which were gradual and persistent, IC50 being 2.6 X 10(-8), 2.7 X 10(-8) and 5.4 X 10(-7) mol/l, respectively. Dipyridamole (10(-7) mol/l), an adenosine uptake inhibitor, markedly augmented the inhibition evoked by adenosine and ATP, but not that by three N6-substituted adenosines, while theophylline (10(-4) mol/l) almost completely antagonized the inhibitory effects of all purine compounds. IC50 value of adenosine in the presence of dipyridamole (5 X 10(-7) mol/l) was shifted to the left about 50 times from the control, whereas that of L-PIA was virtually unchanged. Tissue-medium ratios indicating uptake of [3H]adenosine, [3H]ATP and [3H]CHA into the segment were 3.23 (s.e.m. = 0.59), 3.59 (s.e.m. = 0.78) and 0.41 (s.e.m. = 0.04), respectively. These results suggest that not only adenosine and ATP but also these N6-substituted adenosines are potent agonists for the P1 receptor, implying a similarity between P1 and A1 receptor in a functional role and these purine compounds may thereby modulate cholinergic neurotransmission by altering adenylate cyclase activity.     

Bacterial infection and rapid laboratory microbial methods

The key to treatment of bacterial infectious diseases is always to quickly identify the causative organism and understand its resistance to drugs. Recent progress in microbial laboratory methods has permitted rapid detection and identification of pathogenic organisms. Rapid test methods are classified into culture and non-culture methods. Non-culture methods are based mainly on immunoassay for detection of antigen or antibody of pathogenic organisms, but also include the DNA probe method and the RNA probe method. Immunoassay is achieved by fluorescent antibody techniques, agglutination and ELISA. On a related note, monoclonal antibodies have been developed with steady progress. For culture methods, commercial bacterial identification kits and automated instruments, all of which permit quicker identification than with conventional methods, are now used in a large number of laboratories. Quick identification with these automated instruments is possible owing to optical determination of drug resistance. Some automated instruments are capable of rapidly detecting bacteria in the sample. For example, Bactec, used for quick diagnosis of bacteremia, measures CO2 produced by bacteria in the culture bottle during the metabolic process, permitting early detection of bacterial proliferation. Other methods are available in which ATP produced by bacteria is measured on the basis of bioluminescence or chemiluminescence.     

ANTI-ISCHAEMIC AND VASOSPASMOLYTIC EFFECTS OF A NOVEL Ca2+ CHANNEL BLOCKER, SD-3211, IN VITRO

1. The present study was undertaken to determine the vasospasmolytic activity of a novel non-dihydropyridine type of Ca2+ channel blocker, SD-3211, in isolated canine coronary arteries and its ability to reduce myocardial ischaemic damage in isolated perfused rabbit hearts. 2. The vasospasmolytic effect of SD-3211 was investigated using 3,4-diaminopyridine-induced rhythmic contraction, in comparison with its enantiomer (SD-3212), nicardipine and diltiazem. SD-3211 was shown to reduce the peak tension and increase the contraction frequency. The order of potency for the relaxation of the peak tension was as follows: nicardipine greater than SD-3211 greater than diltiazem greater than SD-3212 and being compatible with that for the relaxant effects of these compounds on KCl-induced contraction in the same specimen. 3. Furthermore, the effect of SD-3211 on myocardial damage due to global ischaemia for 60 min followed by 60 min of reperfusion was examined. SD-3211 at a concentration of 2 X 10(-8) mol/L was given for 40 min before and again for 60 min after the ischaemia. SD-3211 attenuated the increase in leakage of creatine phosphokinase from the hearts and the decrease in pH of perfusate during reperfusion, while concomitantly providing a significant improvement in the post-ischaemic recovery of developed tension. 4. These results suggest that SD-3211 has properties to reduce coronary vasospasm and to provide protection against ischaemic damage, both of which may have beneficial actions in the treatment of ischaemic heart disease.     

A case of nonocclusive mesenteric ischemia (NOMI) which occurred in a patient with torsion of gallbladder]

We report a case of nonocclusive mesenteric ischemia (NOMI) which occurred in a patient with torsion of gallbladder. A 91-year-old woman was admitted to the hospital and was diagnosed of acute cholecystitis. The next day, she went into shock. Then, we diagnosed her illness as torsion of gallbladder by computed tomography and ultrasonography, and performed an emergency operation. After cholecystectomy, it was recognized that the wide range of the small intestine had become necrotic sporadically. We diagnosed it as NOMI, and performed the wide resection of the small intestine followed by making double stomas. There is no previous report of NOMI associated with torsion of gallbladder. We guess the cause of NOMI in this case would be dehydration because of gallbladder torsion. NOMI has high mortality. Early diagnosis and early treatment are of great importance in NOMI.     

Pathological Features of Virus Infections of the Central Nervous System (CNS) in the Acquired Immunodeficiency Syndrome (AIDS)

Neurological disorders are a common cause of morbidity and mortality in the acquired immunodeficiency syndrome (AIDS). In this report we describe the neuropathological changes associated with both human immunodeficiency virus (HIV) infection and with the major opportunistic virus infections, cytomegalovirus (CMV), JC papovavirus (JCV) and herpes simplex virus (HSV) seen in AIDS. In addition "in situ" hybridization studies have been employed for the detection of virus genomic material in each case and the usefulness of this method in supporting the pathological diagnosis is demonstrated. Mechanisms whereby HIV infection results in leukoencephaiopathy and the possible contributing roles of the three opportunistic virus infections are discussed.     

Hepatic resection for a hepatocellular carcinoma larger than 10 cm.

Twenty-one patients with hepatocellular carcinoma (HCC) larger than 10 cm diameter were treated during the 18 year period from 1971 to 1988. The mean tumor size was 13 cm (range 10-18 cm). Nineteen patients (90.5%) had subjective symptoms. Eight patients (38.1%) had alpha-fetoprotein (AFP) levels over 10,000 ng/ml, and in 18 patients (85.7%) the levels were over 20 ng/ml. Nevertheless, only three (14.3%) were detected by AFP. Scintigraphy before 1981 and ultrasonography after 1982 appears to be most helpful for detection of HCC. Nineteen lesions (90.5%) were localized in the right hepatic lobe. Large HCC showed a low incidence of histologically verified concomitant cirrhosis (33%; 7 of 21) and a relatively well preserved hepatocellular function (indocyanine green test; 13.9 +/- 6.6%). Curative resection could be done for all 21 patients. There were three (14.3%) operative deaths. The 1-, 3-, and 5-year survival rates were 72.2, 32.9, and 8.2%, respectively. One patient who underwent a left hepatic lobectomy has survived for over 5 years, with recurrence. There were 14 recurrences (66.7%) in 21 patients: 11 were hepatic and three were in the lungs. In patients with large HCC, surgical resection should be done, provided the clinical status and hepatocellular reserves are adequate.     

Varicella-zoster virus reactivation is an important cause of acute peripheral facial paralysis in children

BACKGROUND: Reactivation of herpes simplex virus type 1 is thought to be a major cause of adult idiopathic peripheral facial paralysis or Bell's palsy. However, few studies have examined the pathogenesis of this condition in children. Serologic assays and polymerase chain reaction (PCR) analysis of paired sera and saliva samples were used here to investigate the causes of acute peripheral facial paralysis in pediatric patients. METHODS: A total of 30 children with acute peripheral facial paralysis were recruited. Paired sera were assayed for evidence of herpesvirus, mumps virus or Borrelia infection. PCR was used to detect herpes simplex virus type 1 and varicella-zoster virus (VZV) DNA in saliva samples. RESULTS: Ramsay Hunt syndrome with accompanying zoster lesions was diagnosed clinically in 2 patients, and VZV reactivation was confirmed serologically. VZV reactivation in the absence of zoster (zoster sine herpete) was diagnosed in 9 patients with either serologic assays or PCR. Thus VZV reactivation was demonstrated in 11 of 30 (37%) patients. The prevalence of VZV reactivation among patients between 6 and 15 years of age was significantly higher than in those younger than 5 years of age (53% versus 9%, P = 0.023). CONCLUSIONS: Our data indicate that VZV reactivation is an important cause of acute peripheral facial paralysis in children, especially those between 6 and 15 years of age.     

Student Research Award in the Undergraduate Degree Candidate category, 30th Annual Meeting of the Society for Biomaterials, Memphis, Tennessee, April 27-30, 2005. Monocyte/lymphocyte interactions and the foreign body response: in vitro effects of biomaterial surface chemistry

To determine the effect of biomaterial surface chemistry on leukocyte interaction and activity at the material/tissue interface, human peripheral blood monocytes and lymphocytes were cultured on a series of poly(ethylene terephthalate) (PET)-based biomaterials. Both monocytes and lymphocytes were isolated from whole human blood and separated by a nonadherent density centrifugation method before being plated on PET disks, surface modified by photograft copolymerization to yield hydrophobic, hydrophilic, anionic, and cationic surface properties. Monocytes and lymphocytes were cultured separately, to elicit baseline levels of activity, in direct coculture, to promote direct cell surface interactions, or in an indirect coculture system with both cell types separated by a -0.02-microm Transwell apparatus, to promote indirect paracrine interactions. Monocyte adhesion, macrophage fusion, and lymphocyte proliferation were measured on days 3, 7, 10, and 14 of culture. Results demonstrated that the presence of monocytes increased the activity of cocultured lymphocytes at the biomaterial/tissue interface, while the corresponding presence of lymphocytes increased the activation and fusion of indirectly cocultured monocytes. Biomaterial surface chemistry was also found to have a significant effect on monocyte adhesion and activation, and lymphocyte activity. Hydrophilic surfaces significantly inhibited both initial and longterm monocyte adhesion, and inhibited lymphocyte proliferation at longer time points. Anionic and cationic surfaces both exhibited mild inhibition of monocyte adhesion at prolonged time points and increased levels of macrophage fusion, while cationic surfaces decreased levels of lymphocyte proliferation and inhibited monocyte activity. These results elucidate the complex role of juxtacrine and paracrine interactions between monocytes and lymphocytes in the foreign body response, as well as promote the consideration of hydrophilic surfaces in future designs of implantable biomedical devices and prostheses.