Inhibitory effect of phospholipase A2 isolated from Crotalus durissus terrificus venom on macrophage function

Recent work demonstrated that crotoxin, the main toxin of Crotalus durissus terrificus venom, inhibits macrophage spreading and phagocytic activities. The crotoxin molecule is composed of two subunits, an acidic non-toxic and non-enzymatic polypeptide named crotapotin and a weakly toxic basic phospholipase A₂ (PLA₂). In the present work, the active subunit responsible for the inhibitory effect of crotoxin on macrophage function was investigated. Peritoneal macrophages harvested from naive rats were used. Crotapotin (2.12, 3.75, or 8.37 nM/ml), added for 2 h to the medium of peritoneal cell incubation, did not modify the spreading and phagocytic activities of these cells. On the other hand, the PLA₂ (1.43, 2.86, or 6.43 nM/ml) subunit caused a significant reduction (30, 33, and 35%, respectively) of the spreading activity. The PLA₂ also inhibited the phagocytosis of opsonised zymosan, opsonised sheep erythrocytes, and Candida albicans, indicating that this inhibitory effect is not dependent on the type of receptor involved in the phagocytosis process. The inhibitory effect of PLA₂ was not due to loss of cell membrane integrity, since macrophage viability was higher than 95%. These findings indicate that the inhibitory effect of crotoxin on macrophage spreading and phagocytic activities is caused by the phospholipase A₂ subunit.     

Effect of acute tyrosine depletion in using a branched chain amino-acid mixture on dopamine neurotransmission in the rat brain.

Central dopamine function is reduced by decreasing the availability of the catecholamine precursor, tyrosine, using a tyrosine-free amino acid mixture containing multiple large neutral as well as branched chain amino-acids, which compete with tyrosine for uptake into the brain. Current mixtures are cumbersome to make and administer, and unpalatable to patients and volunteers. Here, we investigate whether individual or limited amino-acid combinations could reduce brain tyrosine levels and hence dopamine function. Measurements of regional brain tyrosine levels, catecholamine and indoleamine synthesis (L-DOPA and 5-HTP accumulation, respectively) were used to identify an effective paradigm to test in neurochemical, behavioral and fos immunocytochemical models. Administration of leucine or isoleucine, or a mixture of leucine, isoleucine, and valine reduced tyrosine and 5-HTP, but not L-DOPA accumulation. A mixture of leucine, valine, and isoleucine supplemented with tryptophan reduced brain tyrosine and L-DOPA, but not 5-HTP. In microdialysis experiments this amino-acid mixture reduced basal and amphetamine-evoked striatal dopamine release, as well as amphetamine-induced hyperactivity. This mixture also reduced amphetamine-induced fos expression in striatal areas. In conclusion, the present study identified a small combination of amino acids that reduces brain tyrosine and dopamine function in a manner similar to mixtures of multiple amino acids. This minimal mixture may have use as a dopamine reducing paradigm in patient and volunteer studies.     

Nephrotic syndrome in a mother and her infant: relationship with cytomegalovirus infection

This case report describes infantile nephrotic syndrome (NS) in a baby girl with a clinically severe cytomegalovirus (CMV) infection. Culture of the baby's urine was positive for CMV and IgM anti-CMV antibodies were detected. After an unsuccessful course of corticosteroids, gancyclovir treatment was started and a remission of cutaneous, pulmonary, and renal symptoms was achieved. As the mother also developed NS at the end of pregnancy, a common etiology could be postulated, although there were no signs of recent CMV infection in the mother, only anti-CMV IgG. The relationship between CMV infection and glomerular disease is still unclear: NS may represent another manifestation of CMV disease.     

Magnetic resonance imaging and Cogan's syndrome

We report the case of a 25-year old man with vestibulocochlear and ocular impairment compatible with Cogan's syndrome. Later on, severe headache developed. CT scan showed an ischaemic lesion in the right frontal lobe. Magnetic resonance imaging demonstrated multiple bilateral nodular lesions on T2-weighted sequences. These were unmodified at a second MRI examination performed six months later. Under corticosteroids, the neurological and ophthalmic symptoms disappeared, but the patient remained deaf. We believe that this patient had vasculitis involving the brain, with infarcts. To our knowledge, no case of Cogan's syndrome with cerebral magnetic resonance imaging has yet been reported.     

Pediatric lupus versus adult lupus role of the laboratory

Systemic lupus erythematosus (SLE) is the archetypical immunologic disease. Approximately 20% of patients present in the first two decades of life. This article highlights some of the differences between pediatric and adult onset lupus.Children are defined as different from adults on the basis of age. Lupus presents with different gender ratios based on hormonal or pubertal status with more significant skewing toward female patients in the childbearing years. Female patients in the childbearing years appear to have a higher relative risk for mortality. Despite this, children have greater disease severity at onset based on the number of patients who present with significant organ inflammation, the amount of corticosteroids required and the abnormalities in lupus serologies including autoantibodies and low complements. Children present frequently with congenital and acquired complement defects. Children have an increased risk of infections that can be confused with lupus. They have a higher risk of serious pneumococcal infection and may have less protection from vaccinations received at the time of disease onset.The clinical immunology laboratory is critical in the diagnosis and treatment of pediatric SLE. The rapid analysis and transfer of laboratory results can be life saving for the child with suspected new onset lupus. The laboratory is also helpful in determining disease activity through analysis of immunologic trends over time in pediatric lupus patients. This is especially important in the noncompliant adolescent patient who has a correlation between disease activity and lupus serologic tests. Finally, the clinical immunology laboratory is an important tool for better understanding of the immunologic phenomena associated with lupus and of disease pathophysiology.     

Natural history of colonization with vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and resistant gram-negative bacilli among long-term-care facility residents.

OBJECTIVE: To determine the natural history of colonization with vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and resistant gram-negative bacilli among long-term-care facility (LTCF) residents. DESIGN: Observational cohort study. SETTING: A 355-bed LTCF with a ventilator unit and a subacute unit. PARTICIPANTS: Residents with colonization or infection with VRE, MRSA, or resistant gram-negative bacilli housed at the LTCF between December 1, 1999, and February 29, 2000. METHODS: Cultures of clinical and surveillance sites were performed at regular intervals. Charts were reviewed for clinical characteristics associated with clearance of colonization. Kaplan-Meier curves were constructed to analyze the number of days to clearance of colonization. RESULTS: Forty-nine residents had 65 episodes of colonization (27 VRE, 30 MRSA, and 8 resistant gram-negative bacilli). Eighteen (28%) of the episodes cleared. The clearance rate was 2.7 episodes per 1,000 person-days. Clearance occurred significantly more often with resistant gram-negative bacilli colonization compared with VRE or MRSA colonization (6 [75%] vs 12 [21%]; P = .007; relative risk, 4.17; 95% confidence interval, 1.26 to 11.8). There was a trend toward longer use of antimicrobial agents among residents with persistent colonization. Infections occurred most frequently with MRSA. The urinary tract was the most common site of infection. CONCLUSION: Among LTCF residents, colonization with resistant gram-negative bacilli is four times more likely to clear than colonization with VRE or MRSA. Performance of surveillance cultures at regular intervals may reduce the need for contact precautions for LTCF residents with resistant gram-negative bacilli colonization.     

Cardiac receptors affect regional flow during acute infarction in conscious rats

This study was conducted to determine if cardiac receptors have a role in the control of the regional circulations during small acute myocardial infarction in the conscious rat. Cardiocirculatory dynamics and cardiac output distribution (microspheres) were measured in conscious rats 24 and 48 h after surgery for left main coronary artery ligation or the sham procedure. Data from animals without treatment were compared to data from animals treated to induce chemical cardiac denervation (85% phenol applied to the supraventricular surface of the heart and the root of the great vessels). The results suggest that neurogenic vasopressor stimuli originating from the heart contribute to changes in peripheral resistance secondary to small, acute, experimentally induced myocardial infarction in the conscious rat.     

A clinical, microbiologic, and radiographic study of deep caries lesions after incomplete caries removal.

OBJECTIVE: Clinical, radiographic, and microbiologic changes in deep caries lesions were assessed after incomplete carious dentin removal and tooth sealing. METHOD AND MATERIALS: Thirty-two teeth with deep caries lesions were studied. Treatment consisted of incomplete excavation of the demineralized dentin, application of calcium hydroxide, and sealing for a 6- to 7-month period. The color and consistency of the dentin were clinically assessed. Differences in radiographic density were assessed by digital image subtraction. Microbiologic samples were obtained from the demineralized dentin before the temporary sealing and after the experimental period. The samples were cultivated on blood agar under aerobic and anaerobic conditions, in Mitis Salivarius agar, and Rogosa selective Lactobacillus agar. RESULTS: Two cases were lost during the study; one presented pulpal necrosis. In the other case, there was pulpal exposure during removal of provisional sealing. In all teeth, the initial demineralized dentin was soft and wet; one lesion was yellow, 21 were light brown, and eight were dark brown. After treatment, the dentin was dry, and 80.00% of specimens were hard, 16.67% were leathery, and 3.33% remained soft. The dentin was light brown in five teeth and dark brown in 25. There was a statistically significant mean difference in radiographic density (pixel intensity), 88.77 +/- 7.02 in the control areas and 94.66 +/- 6.75 in the test areas. The counts of anaerobic and aerobic bacteria, lactobacilli, and Streptococci mutans had decreased significantly by the end of treatment. CONCLUSION: Incomplete removal of carious dentin and subsequent tooth sealing resulted in the arrest of the lesions, suggesting that complete dentinal caries lesion removal is not essential to the control of caries lesions.