Oxidative stress and anti-oxidant status in leprosy patients.

Severe oxidative stress has been reported in leprosy patients because of malnutrition and poor immunity. The purpose of this study was to investigate the serum lipid peroxidation products, serum LDH and important free radical scavenging enzymes, i.e. superoxide dismutase (SOD), and catalase and anti-oxidant glutathione levels and total anti-oxidant status, in different types of leprosy patients. The subjects for this study were normal human volunteers (NHVs, n=14), paucibacillary leprosy patients (PB, n=18), untreated MB patients (MB1, n=18), MB patients under treatment (MB2, n=19), and MB patients released from treatment (RFT) (MB3, n=28). The levels of lipid peroxidation product, malondialdehyde (MDA), and LDH increased significantly (p<0.001) in MB (MB1, MB2, MB3) patients, and both gradually decreased with clinical improvement following MDT. The levels of SOD, catalase and glutathione, and the total anti-oxidant status decreased significantly in MB (MB1, MB2, MB3) patients (p<0.001), in comparison with NHVs. They gradually increased with clinical improvement with MDT. There was no significant variation of these parameters in PB leprosy patients in comparison with healthy volunteers. High free radical activity and low anti-oxidant levels observed in MB (MB1, MB2, MB3) leprosy patients indicate that there is an oxidative stress in MB cases, irrespective of the treatment status and suggest a suitable anti-oxidant therapy to prevent possible tissue injury.

Deliberate self-poisoning with dapsone. A case report and summary of relevant pharmacology and treatment.

We report the case of a 14-year-old girl who deliberately ingested 8-9 g of dapsone and presented with severe methaemoglobinaemia and altered mental status. Prompt treatment with repeated doses of methylene blue and organ support brought about control of the methaemoglobinaemia and averted organ failure.

Serum lactate dehydrogenase in murine leprosy: source and isozymes.

The bulk of the lactate dehydrogenase (LDH) that increases in the serum of mice infected with Mycobacterium lepraemurium (MLM) derives from the liver and corresponds to the isozyme V. MLM-induced granulomas continuously arise in the liver and steadily increase in size until the animal's death. Growing granulomas push the adjacent hepatocytes away and cause them to disrupt and to release their cytoplasmic contents, including LDH. The LDH is then picked up by the infiltrating phagocytes and/or admixed with the circulating blood. Other LDH-containing organs (including the testis with its additional isozyme LDH-X) in the infected or normal animals do not seem to significantly contribute to the serum levels of LDH. The study of the liver-associated histochemical and biochemical changes in this controlled model of murine leprosy allows us to gain insight into the overall pathology of this mycobacteriosis. In some respects this sheds light on the liver involvement in human leprosy; a subject on which results of all sorts have been published.

Lactate dehydrogenase isoenzymes in leprosy patients on multi drug therapy--a preliminary report.

Serum LDH (total) and LDH isoenzymes were studied in leprosy patients undergoing multidrug treatment. Serum LDH (total) did not show any significant difference between normal human subjects and patients but LDH isoenzymes have shown elevated levels in LDH4 and LDH5 in leprosy patients. The M/H ratios were high in leprosy patients and they exhibited a further rise in patients on treatment.

Serum enzymatic changes following infection of mice with Mycobacterium lepraemurium.

Mice injected interperitoneally with 1.5 X 10(8) Mycobacterium lepraemurium develop progressive visceral alterations that are reflected in the lactic dehydrogenase (LDH), glutamate-pyruvate transaminase (GPT), and glutamate-oxalacetate transaminase (GOT) levels. The rise in GPT and GOT levels starts earlier (about 30 days post-infection) than the rise in LDH activity (about 70 days), but the latter shows the most impressive increases. Differences between infected and control groups, however, reach statistical significance only at 75 days (LDH), 90 days (GOT), and 150 days (GPT) post-inoculation, still well before the appearance of obvious external signs of infection (about 240 days in our model). It is suggested that the ratio of enzyme levels in infected to enzyme levels in uninfected animals could be taken as a reliable index to follow the progress of the infection with M. lepraemurium.

Biochemical alterations in the serum of armadillos (Dasypus novemcinctus) infected with Mycobacterium leprae. A preliminary report.

Armadillos (Dasypus novemcinctus) were inoculated with Mycobacterium leprae isolated from lepromas taken from untreated lepromatous patients or from the spleen of an armadillo previously infected with human M. leprae. The effect of the infection on the serum levels of lactic dehydrogenase (LDH), alkaline phosphatase (AlkP), glutamate-oxalacetate (GOT) and glutamate-pyruvate (GPT) transaminases was investigated. In general, there was a good correlation between positive evidences of infection and alterations in the levels of LDH, GOT, and GPT. Although elevations in LDH levels were more striking, elevations in GOT and GPT levels were more consistent with the disease. When an absolute increase in the total LDH activity was not observed in a M. leprae-infected animal, an increase in the level of LDH isozyme V was still clearly evident. Serum levels of alkaline phosphatase were not affected by the disease. The ratio GOT/GPT (greater than 1.0) in the infected animals reflected and supported the chronic nature of the disease and the liver involvement. The enzymatic alterations are not, however, specific for leprosy.

Characterization of macrophage function in Mycobacterium lepraemurium-infected mice: sensitivity of mice to endotoxin and release of mediators and lysosomal enzymes after endotoxin treatment.

Mycobacterium lepraemurium (MLM) infection increases the sensitivity of mice to lipopolysaccharide (LPS) as do infections with other intracellular parasites. Tumour necrosis factor (TNF), lymphocyte activating factor (LAF) and increased levels of various lysosomal and cytoplasmic enzymes were found in serum samples taken 2 h after intravenous injection of a small dose of LPS suggesting that damage to a variety of cell types, including macrophages, had occurred. Sera from moribund MLM-infected mice not injected with LPS also demonstrated significant levels of TNF compared with controls. Intravenous injections of silica into leprous mice also led to increased levels of serum lysosomal and cytoplasmic enzymes but did not give rise to a significant amount of TNF or LAF. Moreover, in contrast to LPS treatment, the injection of silica did not lead to the death of leprous mice. These findings suggest that the phagocytic cells of the infected animals did not contribute to the production of these mediators after LPS challenge. Rather, the non-phagocytic granuloma macrophages or other unidentified cell types seemed to provide the main source of the monokines TNF and LAF in vivo in the present model. These mediators may have important implications for the immunopathology of MLM infection.

[Effect of suboptimal temperature of cultivation on the dehydrogenase activity of blood monocytes in normal persons and patients with leprosy]. / Vliianie suboptimal'noi temperatury kul'tivirovaniia na degidrogenaznuiu aktivnost' monotsitov krovi zdorovykh i bol'nykh leproi liudei.

The activity of succinate, lactate and glucose-6-phosphate dehydrogenases was studied in blood monocytes of 15 healthy donors and 20 patients with lepromatous leprosy. Cytochemical reaction was assessed photometrically. The total extinction in monocytes, relative activity and the dehydrogenase ratio were measured. The data obtained have shown that in healthy donors, the decrease of the culture temperature to 25 degrees C leads to the prevalence of glycolysis and the fall in the activity of the pentose-phosphate shunt. In leprosy patients, the dehydrogenase activity at a culture temperature of 37 degrees C is similar to that in healthy subjects at a temperature of 25 degrees C. Reduction of the monocyte culture temperature in leprosy patients does not cause any significant changes in the dehydrogenase activity of monocytes.

Anomalous isoenzymes of lactate dehydrogenase in sera of patients with leprosy.

In an earlier study (Saoji et al, 1980) we looked for anomalous (additional) isoenzymes in homogenates of 17 active and 25 of regressing lepromatous leprosy, three of erythema nodosum leprosum, eight of BT, 19 of TT and one of indeterminate leprosy. Anomalous bands were found in 17 cases. They correlated with large numbers of viable organisms and were thought to originate from Mycobacterium leprae. This communication describes the serum LDH isoenzymes of the same 78 cases. Six of 17 cases with anomalous LDH isoenzymes in tissues showed anomalous bands even in serum samples. The bands were much fainter but had similar mobility in terms of Ef values. Therefore, LDH isoenzymes originating from Mycobacterium leprae were discernible in sera of cases, though not on the same scale as in the tissues.

Dapsone induced hypohaptoglobinemia in lepromatous leprosy patients.

Dapsone has been used in various dermatological disorders and in leprosy. One of the main side effects of dapsone therapy is anemia, mostly hemolytic. We aimed at finding the effect of dapsone therapy on serum haptoglobin levels which could be an indirect evidence for intravascular hemolysis, supported by secondary investigations such as liver functions (serum lactic dehydrogenase, alkaline phosphatase, bilirubin), blood hemoglobin levels, urinary excretion of urobilinogen, and erythrocytes. As in other infectious conditions, haptoglobins were raised in untreated lepromatous cases, compared to controls (p less than 0.05). Dapsone treatment of 100 mg daily for 14 days brought down the haptoglobin level significantly as compared to the untreated cases and the controls (p less than 0.05). An elevated alkaline phosphatase and lactate dehydrogenase indicate some liver dysfunction following dapsone therapy. A significant drop in blood hemoglobin level and a concomitant increase in serum bilirubin, urinary excretion of urobilinogen, and a significant fall in the serum hemoglobin binding capacity (haptoglobin level) following treatment with dapsone are quite suggestive of mild intravascular hemolysis.

[Levels of lactate dehydrogenase isoenzymes in the serum of Hansen's disease patients]. / Perfil de las isoenzimas de la dehidrogenasa lactica en el suero de pacientes hansenianos]

The LDH isoenzymes levels in fresh serum of seven patients affected by different forms of hanseniasis from Argentina, were measured by acrylamide electrophoresis. In all cases the LDH-4 fraction was found elevated; on the contrary, LDH-2 was reduced. The LDH-5 fraction was detected in only three serums, all of them significantly increased when compared with controls.

Biochemical, immunological and genetic studies in leprosy. I. Changes in serum lactate dehydrogenase isoenzymes, creatine phosphokinase and aldolase activity in different forms of leprosy.

Serum lactate dehydrogenase isoenzymes, creatine phosphokinase and aldolase activity were determined in healthy control subjects and in lepromatous and tuberculoid leprosy patients from Ethiopia. Sera from lepromatous patients showed a higher total LDH activity compared with control subject. The values for tuberculoid leprosy patients were similar to those of controls. Sera from normal healthy controls showed a higher proportion of LDH-H form (72%) while lepromatous leprosy patient's sera exhibited a higher proportion of LDH-M form (55%). Tuberculoid leprosy patients showed a pattern similar to that of healthy controls. A possible significance of these observations is discussed. No significant variations were observed in fructose-1,6-diphosphate aldolase activity within the different types of disease and controls. Although creatine phosphokinase levels in different types of leprosy decreased significantly from those of normal healthy, it falls within the reported variation of the activity in normal sera.