Pharmacological analysis of extracellular dopamine and metabolites in the striatum of conscious as/agu rats, mutants with locomotor disorder

The as/agu rat is a spontaneously occurring mutation which exhibits locomotor abnormalities, reduced tyrosine hydroxylase levels in the substantia nigra and lower extracellular levels of dopamine. The animal could represent a model of some human locomotor disorders. High-potassium medium evoked a 460% rise of dopamine levels in control rats but double this in mutants. Amphetamine increased extracellular dopamine by 710% in controls and 1480% in mutants. Clorgyline produced a small increase of dopamine levels in controls but an 1170% increase in mutants. The uptake inhibitor nomifensine increased dopamine levels by 910% in controls but only 270% in mutants. After treatment with benserazide plus L-DOPA, an acute injection of L-DOPA evoked a release of dopamine which was twice as large in the as/agu rats compared with controls. The results show reduced extracellular dopamine in as/agu rats when the locomotor disorder is apparent, but there has been little loss of tyrosine hydroxylase. The responses to drugs are qualitatively different from those obtained using 6-hydroxydopamine.Overall, the effects of compounds affecting aminergic neurons suggest that one possible mechanism for the neuronal abnormality in as/agu rats is a defective regulation of dopamine release from striatal terminals.     

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.     

Ultrastructural markers of lymph nodes in patients with acquired immune deficiency syndrome and in homosexual males with unexplained persistent lymphadenopathy. A quantitative study

To determine if vesicular rosettes (VR), tubuloreticular structures (TRS), and "test-tube and ring-shaped forms" (TRF) are characteristic ultrastructural features of the syndromes of acquired immune deficiency (AIDS) or of unexplained persistent lymphadenopathy (PLS), the authors studied lymph nodes from nine patients with PLS, two patients with AIDS, and seven controls by electron microscopy. An average of 122 lymphocytes per case were photographed. VR were present in only 0.37% of lymphocytes in 4 of 11 index cases and were mimicked by grouped vesicles and degenerating multivesicular bodies (MVB). TRS were found in 10 of 11 index cases, compared with only one of seven controls (P less than 0.01). In the index cases, they were more frequent in AIDS (mean 21%) than in PLS lymphocytes (mean 4%) (P less than 0.05). MVB were found in all index cases and five of seven controls and were more frequent in index lymphocytes (mean 19%) than in controls (mean 5%) (P less than 0.01). TRF were found in one Haitian male with AIDS, where they were present in 4% of lymphocytes. VR are infrequent and indistinct. MVB probably reflect the reactivity of the lymphocytes. TRF is not a feature of PLS. The authors conclude that there are no pathognomonic ultrastructural markers of AIDS or PLS but that TRS are characteristic of both syndromes and occur frequently enough to be supportive to the diagnosis of AIDS and PLS.     

DNA evidence of Borrelia lonestari in Amblyomma americanum (Acari: Ixodidae) in southeast Missouri

Amblyomma americanum collected near Lake Wappapello, Missouri, tested positive for Borrelia lonestari using polymerase chain reaction and sequence analyses of B. lonestari 16S rRNA and flagellin (flaB) genes. Twelve pools containing a total of 214 nymph or adult ticks contained evidence of infection with B. lonestari (minimum prevalence 5.6%). These data suggest that persons in southeast Missouri are at risk for exposure to B. lonestari after A. americanum tick bite, a possible cause of erythema migrans-like rash illness in this region. Derivation of the complete coding sequence for B. lonestari flaB is also reported.     

Interaction of technetium 99m-labeled teboroxime with red blood cells reduces the compound’s extraction and increases apparent cardiac washout

Background

^99mTc-labeled teboroxime shows high myocardial extraction in both in vivo animal and in vitro cell culture and isolated heart studies. Whereas in vivo studies show rapid myocardial clearance of teboroxime, in vitro cell culture and isolated heart studies show slower washout comparable to that of²⁰¹Tl. Binding of teboroxime to blood components may contribute to these conflicting results.

Methods and Results

We measured teboroxime extraction in the isolated blood-perfused rabbit heart after injection in saline solution, brief incubation in red blood cell perfusate, or 4-hour incubation with human red blood cells. Teboroxime in saline solution showed high extraction (E_max=0.89±0.02; E_net=0.69±0.02), whereas brief incubation in perfusate (E_max=0.60±0.06; E_net=0.48±0.05) or prolonged incubation with human red blood cells (E_max=0.43±0.09; E_ne=0.38±0.07) resulted in reduced extraction. Teboroxime clearance was similar for all groups and was slower than²⁰¹Tl clearance. Analysis of total residual cardiac teboroxime (comparable to external imaging) showed that teboroxime clearance was biexponential. Reduced extraction of teboroxime in red blood cells resulted in an increased size of the rapidly clearing (unextracted) fraction, giving the appearance of rapid myocardial washout.

Conclusions

Teboroxime has a high myocardial extraction. Binding to blood components reduces teboroxime extraction and increases the rate of cardiac teboroxime clearance.     

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.