Circulating Secretory Phospholipase A2 Activity following Snakebites and Its Relationship with Envenomation Status and Progression of Local Swelling.

We studied whether circulating secretory phospholipase A2 (sPLA2) activity reliably distinguished patients with snakebite envenomation from those with nonvenomous/dry snakebites, and whether patients with progressive local swelling had persistence of circulating sPLA2 activity despite antivenom treatment. We prospectively enrolled adults presenting to the emergency with a history of snakebite in the past 24 hours. We estimated circulating sPLA2 activity at baseline before antivenom administration and after 48 hours in those with envenomation. We enrolled 52 patients with snakebites (mean age 39.3 ± 12.6 years; 35 [67%] men), and 16 patients with infective cellulitis as controls. Thirty patients had local ± systemic envenomation; 15 were classified as dry/nonvenomous bites; and envenomation status was unclear in seven patients. Baseline sPLA2 activity was significantly higher in snakebite patients than that in those with infective cellulitis (4.64 [3.38-5.91] versus 3.38 [1.69-4.01] nmol/minute/mL; P = 0.005). Among patients with snakebites, sPLA2 activity in the highest quartile was significantly associated with envenomation (12 of 27 versus two of 22; P = 0.010). However, median sPLA2 activity did not differ significantly between patients with envenomation and the rest. Baseline sPLA2 activity was significantly associated with the maximum extent of limb swelling (P = 0.031 for trend). In envenomed patients, circulating sPLA2 activity significantly decreased after 48 hours compared with the baseline (5.49 [3.38-8.86] versus 3.38 [2.53-4.64]; P = 0.003) including those with progressive swelling. Although circulating sPLA2 activity was elevated following snakebites, its sensitivity to diagnose envenomation appears to be limited. Administration of more antivenom after systemic manifestations had reversed might not benefit patients with progressive local swelling.

[Impact of antioxidative therapy on state of enzymic redox-system of glutathione in patients with phlegmons of maxillofacial area].

Traditional and antioxidative therapy (retinol and alpha-tocopherol) was done by therapeutic course to 18 patients with phlegmons of maxillofacial region. In the peripheral blood leucocytes and tissues (skin, muscle) of the patients with phlegmons there were determined glutathione reductase activity, glutathione peroxidase activity and content of glutathione. Disbalance of glutathione enzyme redox system in leucocytes of patients with phlegmons was corrected by comprehensive therapy after 1 week. Spirman's correlation analysis showed positive correlation between glutathione depended enzymes in skin and muscle of patient with phlegmons before and after therapeutic course.

Increased intracellular activity of matrix metalloproteinases in neutrophils may be associated with delayed healing of infection without neutropenia in myelodysplastic syndromes.

To investigate the influence of the intracellular activity of type II and type IV collagenases [matrix metalloproteinases (MMP)-2, MMP-8, and MMP-9] in neutrophils from patients with myelodysplastic syndromes (MDS), we tried to measure intracellular activity using flow cytometric techniques. We also studied the clinical features of patients showing high activity. The intracellular collagenase activity, expressed as a ratio to the standardized fluorescence intensity, in patients with MDS was significantly higher than normal volunteers (19.5+/-14.8 vs 13.3+/-6.8, p=0.024). The difference among subcategories of MDS according to the French-American-British (FAB) and WHO classifications was not significant. No significant influence of three variables of the International Prognostic Scoring System (IPSS) was seen on activity. Of 8 patients with activity of more than 26.9 (mean+2 standard deviations of normal controls), 5 experienced an episode of delayed healing of infection without neutropenia, while 1 of 43 patients with activity of less than 26.9 experienced such an episode (p=0.0002). The average collagenase activity of six patients with delayed healing of infection without neutropenia (44.7+/-28.9) was significantly higher than that of other MDS patients (16.0+/-7.1, p=0.005) (Fig. 4). It was also significantly higher than the activity of the control group (13.3+/-6.8, p=0.011). Our report suggests that increased collagenase activity in neutrophils may delay healing of infection. In addition, we suggest that increased collagenase activity may be an independent prognostic factor for the susceptibility to severe infection in MDS.

Compartmentalised inducible nitric-oxide synthase activity in septic shock.

BACKGROUND: Previous experimental studies support a role for inducible nitric-oxide synthase (iNOS) in the pathogenesis of severe sepsis. The aim of the study was to characterise iNOS activity in different tissues in patients with septic shock. METHODS: 13 consecutive patients with septic shock caused by cellulitis were enrolled. Skin, muscle, fat, and artery samples were obtained from normal, inflamed, and putrescent areas to measure iNOS activity, and concentrations of tumour necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta). In two patients, iNOS activity was also assessed in peripheral blood mononuclear cells (PBMC) incubated with microorganisms causing the sepsis, or in macrophages isolated from suppurating peritoneal fluid incubated with IL-1beta. FINDINGS: Compared with normal and inflamed areas, iNOS activity was increased in putrescent areas for muscle (71-fold [95% CI 20-259] vs normal areas, 69-fold [19-246] vs inflamed areas; p<0.01 for each) and for fat (68-fold [23-199] and 49-fold [18-137], respectively; p<0.01), but not for skin. Compared with normal areas, putrescent areas of arteries showed increased iNOS expression (1280-fold [598-3153]; p<0.01). Compared with normal areas, TNFalpha and IL-1beta were increased in putrescent areas of arteries (223-fold and 41-fold, respectively; p<0.01 for each). PBMCs and tissue macrophages expressed iNOS. Plasma nitrite/nitrate concentrations inversely correlated with mean arterial pressure and systemic vascular resistance. INTERPRETATION: In human septic shock we found that iNOS activity is compartmentalised at the very site of infection and parallels expression of TNFalpha and IL-1beta. PBMCs and tissue macrophages can be a cellular source for iNOS.

[The effect of endogenous intoxication on liver function in patients with phlegmons of the face and neck]. / Vliianie éndogennoi intoksikatsii na sostoianie pecheni u bol'nykh flegmonami litsa i shei.

The function of the liver is assessed in patients with maxillofacial phlegmons suffering from endogenic intoxication of different severity. The most marked changes of the enzymatic activity of the liver were observed in patients with progressive phlegmons and complications thereof (mediastinitis or sepsis) involving endotoxicosis of the second or third degree. The authors come to a conclusion on the functional hepatic failure in patients with phlegmons of the face and neck, which fact should be borne in mind when planning combined therapy of this patient population.

[Fluorometric method of determining prolylendopeptidase activity in human erythrocytes in normal and pathologic conditions]. / Fluorometricheskii metod opredeleniia aktivnosti proliléndopeptidaz v éritrotsitakh liudei v norme i pri patologicheskikh sostoianiiakh.

A highly sensitive fluorometric method for determination of prolylendopeptidase (PE) activity in human erythrocyte hemolysates in the presence of hemoglobin has been developed. The method is based on measurement of fluorescence of 4-methyl-7-aminocoumarine released in the course of enzymatic reaction from the substrate Z-glycyl-proline-4-methylcoumarine-7-amide. A correlation was introduced for the quenching of fluorescence by hemoglobin. The method is suitable for the determination of PE activity in human erythrocyte hemolysates in various pathological states. The dependence of PE activity on the incubation time, protein and substrate concentrations were studied using the 1,200-fold purified preparations of prolylendopeptidase II. The values of PE activity in erythrocyte hemolysates of healthy donors and in those of patients with odontogenic phlegmons of maxillary-facial area were virtually identical. PE activity in erythrocyte hemolysates of stored blood was 5 times lower than that in the cell hydrolysates of fresh blood. The PE activity was not observed in blood serum of fresh and stored blood of healthy persons and of patients with acute inflammatory processes of maxillary-facial area, as well as in blood serum of patients with hepatitis and glomerulopephritis.

[Enzymatic status of leukocytes in pyo-inflammatory diseases of the soft tissues and their changes caused by pyrimidine derivatives]. / Fermentnyi status leikotsitov pri gnoino-vospalitel'nykh zabolevaniiakh miagkikh tkanei i ego izmeneniia pod vliianiem pirimidinovykh proizvodnykh.

It has been established that data of cytochemical investigation of leukocytes can show the severity of the pathological process and contribute to prognosing further development of pyo-inflammatory disease. Pyrimidine derivatives have a pronounced normalizing effect on the enzyme activity of leukocytes.

[Changes in leukocyte lysosomal acid and alkaline phosphatase activity in acute surgical diseases of the abdominal cavity organs]. / Izmeneniia aktivnosti kisloi i shchelochnoi fosfataz lizosom leikotsitov pri nekotorykh ostrykh khirurgicheskikh zabolevaniiakh organovbriushnoi polosti.

To discriminate initial stages of an inflammation from its destructive forms, the authors studied the leucocyte lysosome activity at different stages of inflammatory processes in abdominal organs. 90 patients and 30 practically healthy individuals were examined. The indices of acid and base phosphotase activity were found to rise together with the progress of an inflammatory process. A nomogram, permitting to determine with a rather high precision the stage and direction of the process, was made up on the grounds of the established reguliarity after the mathematical procession of the obtained figure data.