Early intervention with probiotics and metformin alleviates liver injury in NAFLD rats via targeting gut microbiota dysbiosis and p-AKT/mTOR/LC-3II pathways.

Non-alcoholic fatty liver disease (NAFLD) constitutes a major health problem worldwide and intimately links with obesity and diabetes. This study aimed to explore the therapeutic impact of early treatment with metformin (MTF) alone or in combination with Lactobacillus reuteri DSM 17938 (L. reuteri) + metronidazole (MTZ) in male Sprague Dawley rats with high-fat diet (HFD)-induced NAFLD. Hepatic steatosis was induced by feeding rats HFD for 6 weeks. MTF (150 mg/kg/day) or L. reuteri (2 × 109 colony forming unit/day) were given orally for 4 weeks; meanwhile, MTZ (15 mg/kg/day, p.o.) was administered for 1 week. Administration of L. reuteri + MTZ in combination with MTF produced a superior effect concerning insulin resistance (IR), lipid profile, liver function, oxidative stress, inflammatory and autophagic markers than using each treatment alone. Besides, this combination resulted in disappearance of steatosis, inflammation and vacuolation within hepatic architecture. Moreover, it normalized short chain fatty acids (SCFAs) as well as Firmicutes and Bacteroidetes faecal contents. In conclusion, early treatment with L. reuteri + MTZ in combination with MTF could prevent NAFLD progression and liver injury through targeting gut dysbiosis, inflammation and autophagic pathways.

Mirazid shows insignificant activity against ovine fascioliasis.

In a recent study, the fasciolicidal activity of Mirazid (a myrrh-derived drug) and its effect on the function and histopathology of host liver were investigated in Egyptian sheep, with triclabendazole (TCBZ) used as the positive control. Sheep were infected with metacercariae (150/animal) and treated 3 months later, either with Mirazid (10 mg/kg/day for six consecutive days) or TCBZ (a single dose of 10 mg/kg), or left untreated, as controls. When the animals were killed 4 weeks after the end of treatment, no Fasciola flukes or eggs could be found in the animals given TCBZ but the number of flukes found in the Mirazid-treated animals was only 6% lower than that recorded in the untreated sheep (a statistically insignificant difference). In terms of their Fasciola egg loads, serum concentrations of hepatic enzymes and hepatic histopathological changes, the Mirazid-treated sheep appeared very similar to the untreated, infected animals. The TCBZ-treated animals, in contrast, showed remarkably little evidence of hepatic pathology. It therefore appears that, in the treatment of ovine fascioliasis, at least some batches of Mirazid have little, if any, value.

Schistosoma haematobium (Egyptian strain): rate of development and effect of praziquantel treatment.

This study investigates the development of the Egyptian strain of Schistosoma haematobium and the resultant immunohistopathology and biochemical changes in organs affected. In addition, the response of different developmental stages of S. haematobium worms to praziquantel (PZQ) was examined. Schistosoma haematobium-infected hamsters were classified into 4 groups and were treated at day 35, 55, 75, and 95 postinfection (PI), respectively. Each group was subdivided into 3 subgroups. Two of them were treated orally with PZQ (300 mg/kg or 500 mg/kg divided equally on 2 consecutive days), and the third group was left without treatment. Treated groups were killed 20 days posttreatment. Infection with S. haematobium became patent 73 days PI; tissue egg load and worm fecundity were higher at 95 days and maximal 115 days PI, with an oogram pattern comparable to that in Schistosoma mansoni infection. In the liver, small cellular granulomas were observed 75 days PI, with preponderance of CD4+ T-cell phenotypes. In the urinary bladder, only submucosal focal Brunn's-nest formation and angiogenesis without typical granulomas were observed. Ninety-five and 115 days PI, confluent granulomata with multiple eggs in the center were observed in the liver and urinary bladder, with a preponderance of CD8+ positive T cells in the liver and hyperplasia of the urinary bladder epithelium with cystitis cystica and papillae formation. One hundred percent worm eradication was recorded with the higher dose of PZQ in animals treated 75 and 95 days PI. In conclusion, in spite of the long prepatent period of the Egyptian strain of S. haematobium, sensitivity to PZQ was recorded soon after infection. Granulomata were similar to those of S. mansoni in the livers and urinary bladders, but they were confluent with multiple eggs in the centers, hyperplasia of the urinary bladder urothelium with cystitis cystica, papillae, and Brunn's-nest formation predictive of malignant changes with no hepatocyte dysplasia.

Artemether as adjuvant therapy to praziquantel in murine Egyptian schistosomiasis mansoni.

We investigated the activity of artemether (ART) against different developmental stages of schistosomes alone and in addition to praziquantel (PZQ). ART was administered orally (400 mg/kg) 4 and 6 wk postinfection (PI), 4 and 5 wk PI, or 4 or 6 wk PI alone and in addition to oral PZQ (500 x 2 mg/kg) 6 wk PI. Mice were killed in parallel to infected untreated controls 8 wk PI. Parasitological parameters and histological changes in the liver were studied. ART given 4 and 6 wk PI reduced worm burdens by 59 and 55% and tissue egg load by 96 and 90%, respectively. Moreover, eggs in different developmental stages were not found. The reduction in worm and egg burden (63 and 58%, and 96 and 99%, respectively) in mice treated with ART 4 and 5 wk or 4 and 6 wk PI was comparable with that in ART-treated mice at 4 or 6 wk PI. Compared with PZQ alone, combined treatment of PZQ and ART (4 and 5 wk or 4 and 6 wk PI) did not enhance worm eradication, but there was a complete absence of parasite eggs. Livers revealed no granulomata when ART was given 4 and 5 wk or 4 and 6 wk PI, with minimal central necrosis in those treated 4 and 6 wk PI. In conclusion, combined treatment of ART (4 and 6 wk PI) and PZQ resulted in >90% worm eradication and amelioration of Schistosoma mansoni eggs from the tissues, with minor histological changes in the liver.

Effect of combined praziquantel and recombinant glutathione S-transferase on resistance to reinfection in murine Schistosomiasis mansoni.

This study was undertaken to evaluate the effect of recombinant Schistosoma mansoni-26 Glutathione S-transferase (rSm 26 GST) or soluble egg antigen (SEA) alone and in addition to praziquantel (PZQ) on the state of resistance to S. mansoni reinfection. The associated changes in the immune responses were evaluated. The experimental group of mice were injected intravenously before S. mansoni infection (80 cercariae/mouse) either with rSm26 GST (1 microgx4) or SEA (10 microgx4) in addition to PZQ (2x500 mg/kg) administered 6 weeks post-infection. Seven control groups were used, three of them were the infected (80 cercariae/mouse), the challenged (240 cercariae/mouse) and the infected challenged controls (80+240 cercariae/mouse). The rest of the four groups were the treated controls receiving: the GST-Lyzate, rSmGST, SEA and PZQ in the same doses and at the same timings. Challenge infection was conducted for all the groups 8 weeks post-infection. Animals were sacrificed 3 weeks post-challenge. After sacrifice animals were perfused and percentage resistance to reinfection was calculated. Immune responses were assessed by the measurement of hepatic granuloma diameter, intralesional T-cell phenotypes and serum immunoglobulin isotypes. The highest percentage of resistance to reinfection was observed in rGST-treated group while the lowest percentage of resistance was detected in PZQ-treated group. Whereas in mice receiving combined rGST or SEA and PZQ, percentage resistance to reinfection was significantly higher than that in PZQ treated mice. The remarkable reduction in granuloma diameter in rGST-treated group with or without PZQ was associated with decrease in the intralesional L(3)T(4)(+) and increase in Lyt(2)(+) T-cell phenotypes. However, no special relationship was observed between the percentage of resistance and the changes in granuloma diameter or intralesional T-cell phenotypes. The increase in percentage resistance to reinfection was found accompanied by increased anti SWAP IgE. Combined rGST and PZQ provided the complementary goals of improved state of resistance to reinfection 'which was compromized after cure with PZQ' and the maximal reduction in granuloma diameter.

Efficacy of an antipathology vaccine in murine schistosomiasis administered with and without chemotherapy.

This study was undertaken to study the efficacy of praziquantel (PZQ) in potentially tolerized Schistosoma mansoni infected, egg-injected C57BL/6 mice, receiving multiple administrations of soluble egg antigen (SEA) intravenously (i.v.). Four animal groups were studied. Experimental group I received four injections of SEA (10 micrograms) intravenously on days -7, -5, -3 and -2 before infection and PZQ orally (500 mg/kg over two consecutive days 7 weeks post-infection. Three control groups received the following treatment: group II received the same tolerizing dose of SEA without PZQ, group III received PZQ in the same dose and at the same timing. Group IV received S. mansoni infection and egg injection 8 weeks post-infection and served as an infected, egg-injected control. Egg injection was conducted 8 weeks post-infection using viable S. mansoni eggs via the tail vein. Animals were killed 16 days post-egg injection, i.e. 10 weeks post-infection. After sacrifice, lungs and livers were removed for histopathological study and measurement of granuloma diameters. Spleens and serum were collected for the assay of lymphoproliferative response to SEA and antischistosomal immunoglobulins. The worm and egg burdens were also studied. Compared to infected, egg-injected untreated controls, repeated i.v. administrations of SEA down-regulated egg-injected (pulmonary) and egg-deposited (hepatic) granulomas and the lymphoproliferative response to SEA. Antischistosomal IgG level was increased. Susceptibility to S. mansoni infection was not found to be different from that in the infected, egg-injected controls. PZQ in the dose used caused complete eradication of worms, disappearance of immature egg stages, decrease in the number of mature eggs and an increase in the number of dead eggs. Hepatic granuloma diameter, lymphoproliferative response to SEA and IgG level were reduced. In mice receiving a combined regimen of multiple SEA administrations and PZQ with down-regulated granuloma and reduced lymphoproliferative response to SEA, the efficacy of PZQ was the same as in mice receiving PZQ alone. This was shown by comparable grades of worm and egg reduction. The histopathological examination of liver and lung sections in the different treated groups revealed moderate to small-sized hypocellular granulomas. Although no statistically significant difference was recorded between the mean granuloma diameters of the experimental group receiving both the tolerizing dose of SEA and PZQ compared to the group receiving the tolerizing dose of SEA without chemotherapy, this experimental group showed the least associated histopathological parenchymal changes. It appears from this work that combined SEA and PZQ provided many complementary goals; a reduction of egg-induced pathology, minimal parenchymal changes and the eradication of worms.

Schistosoma mansoni: egg granuloma reduction in challenged mice after vaccination with irradiated-attenuated cercariae.

Response of Swiss albino mice vaccinated with irradiated-attenuated cercariae or repeatedly infected with normal cercariae of Schistosoma mansoni were known to develop resistance to reinfection. The mean (+/- SD) of the hepatic granuloma numbers and diameters for vaccinated-challenged group (I) were 2 +/- 0.89/1mm2 and 116 +/- 11.5 microns, for repeatedly infected group (II) were 2 +/- 0.63/1mm2 and 2 +/- 0.89/1mm2 and 195 +/- 11.8 microns and for control group (III) were 4 +/- 1.36/1mm2 and 140 +/- 12.3 microns respectively. Mean of the diameter of the granulomas were significantly smaller in the group vaccinated with irradiated cercariae than the other two groups. Most of the granulomas in groups I and II were fibro-cellular while all granulomas in group III were cellular. Predominent cell types of the granulomas were lymphocytes in groups I and II and eosinophils in group III. The incidence of focal hydropic and fatty degenerations, necrosis and prominent kupffer cell hyperplasia were lower in group I. These results supported that granuloma size reduction in all vaccinated animals were apparently effective in sequestering egg toxins and reduced hepatocytes damage. The present study gives encouragement that a vaccine to enhance protection against disease in human schistosomiasis is possible.

Immunoregulatory potential of exogenous Schistosoma mansoni soluble egg antigen in a model of experimental schistosomiasis--I. Regulation of granuloma formation in vivo.

This study was undertaken to assess the optimum conditions required to reduce the vigorous host granulomatous reaction around Schistosoma mansoni eggs. Soluble schistosomal egg antigen (SEA) at a concentration of 10 or 100 micrograms protein was administered i.p. or i.v. into unprimed C57BL/6 mice. SEA was injected either alone or in combination with cyclophosphamide (CY) 100 or 50 mg/kg via i.p. route. Seven or 14 days later viable eggs of S. mansoni were injected via the tail vein into treated groups and untreated normal controls. Mice were sacrificed 8, 16 and 24 days after the injection of eggs. The lungs were removed for histopathological study, measurement of granuloma diameter and phenotypic analysis of granuloma intralesional T-cell subsets. Compared to untreated controls, the lower concentration of SEA (10 micrograms) administered by the i.v. route 7 days before egg injection, induced a significant reduction in granuloma diameter 16 days after egg injection than that by the i.p. route or at a higher SEA concentration (100 micrograms). Compared to untreated controls, the higher dose of CY (100 mg/kg), given i.p. alone or in combination with 10 micrograms SEA by the i.v. or i.p. route, induced a significant reduction in granuloma diameter, while 50 mg/kg CY did not cause any reduction. The reduction in granuloma diameter by i.v. administration of low SEA concentration alone or in combination with CY IP, was associated with a decrease in the granuloma intralesional L3T4+/Lyt2+ ratio. The decrease in the ratio was due to an increase in Lyt2+ cells. The results suggest that the use of low dose SEA by the i.v. route alone or combined with an immunosuppressive drug ameliorates pathological changes concurrent with S. mansoni infection.

Schistosoma mansoni: IgG reactivity to soluble adult worm antigen preparation (SWAP) in sera of immunized mice with irradiated attenuated and virulent cercariae.

The aim of this work was to identify the antigens, that elicit a greater or unique immune response in the immunized host against Schistosoma mansoni (Egyptian strain) infection. Moreover the difference in immune response to this antigen between mice immunized with radiation-attenuated cercariae or immunized with virulent cercariae were investigated. Immunobloting technique was used to monitor the fine specificity of host IgG to SDS-PAGE separated SWAP in the sera of different test groups immunized with either radiation-attenuated cercariae or low doses of virulent cercariae compared to non-immunized group. Data from this study showed that groups immunized with virulent and irradiated-attenuated cercariae showed 74.7% and 68.3% reduction in worm burden respectively. Differences of humoral immune response of sera of different tested groups against SWAP proteins were definite. Sera of non-immunized mice precipitated non-immunogenic proteins of 87 and 83 KD. SWAP proteins of 106 and 97 KD were identified only by the sera of vaccinated animals with irradiated attenuated cercariae whether challenged or not. Resistant sera from animals immunized by either irradiated-attenuated cercariae or virulent cercariae recognized low molecular weight antigens that ranged from 34 to 52 KD in addition to 57 KD. This indicated that the 106 and 97KD may be the target antigens for protection by radiation-attenuated larvae, while the marker of resistance induced by attenuated or virulent larvae may be 34-52 and 75 KD antigens.

Treatment of experimental schistosomiasis mansoni with praziquantel alone and combined with cimetidine.

In this work, praziquantel (EMBAY 8440, CAS 55268-74-1), an oral antihelminthic drug effective against the three species of schistosomes pathogenic to man, was tested alone and in combination with cimetidine (CAS 51481-61-9), aH2-receptor antagonist having a known potentiative power when combined with other drugs. Both drugs were tested in different doses and regimen either alone or in combination by giving them to S. mansoni infected Swiss albino mice (100 cercariae/mouse) 7 weeks post infection. Cimetidine was tested in doses of 50, 100 and 200 mg/kg for 2 consecutive days; praziquantel was given in doses of 100 and 500 mg/kg for 2 consecutive days. It was found that the best regimen was that of cimetidine and praziquantel when given simultaneously. Both drugs when given in a dose of 100 mg/kg for 2 consecutive days reduced the total worm load by 84.61%, while a percent reduction of 75.1% and 88.9% was recorded in hepatic and intestinal tissue egg load, respectively. Maximum efficacy was recorded when both drugs were given simultaneously at 200 mg/kg for 2 consecutive days. This regimen completely eradicated all schistosome worms and resulted in the maximum reduction in total tissue egg load (92%). The efficacy of this regimen was nearly the same as that of the full dose of praziquantel (500 mg/kg for 2 consecutive days), gave 100% worm eradication and 95% reduction in total tissue egg load.

Detection of circulating anodic antigen before and after specific chemotherapy in experimental murine Schistosomiasis mansoni.

In two groups of mice infected with 60 (group I) and 120 (group II) Schistosoma mansoni cercariae, respectively, the effects of intensity and duration of infection, and of praziquantel therapy (curative vs subcurative dose) on the levels of circulating anodic antigen (CAA), were studied. CAA was measured in trichloracetic acid-treated serum samples with an avidin-biotin enzyme-linked immunosorbent assay (AB-ELISA) using the monoclonal anti-CAA antibody. Total worm burdens, oogram patterns and ova counts/g liver and intestine were followed up. The lowest detectable level of CAA was about 1.0 ng/ml, and was positive with a worm load of 3-5/mouse. CAA levels became already detectable as early as 1-2 weeks post-infection (pi) before any parasitological parameter and showed a significant drop from the 11th-12th week pi onwards. A positive correlation was demonstrated between the CAA level and worm load. Following successful praziquantel therapy, CAA disappeared earlier than any of the other parameters studied.

Schistosoma mansoni: angiotensin converting enzyme activity in mice under the influence of praziquantel and/or captopril.

Murine schistosomiasis is usually associated with hepatic granulomatous lesions together with high serum and granuloma angiotensin converting enzyme (ACE) activity. Praziquantel (PRZ) which is known to reduce granuloma size was studied to show whether this effect is related to changes in ACE activity. Furthermore, captopril was studied to show whether by inhibiting ACE activity, the drug could also affect granuloma size. PRZ, captopril, and their combination led to significant reduction in liver granuloma. However, in normal mice, captopril was shown to increase rather than decrease serum ACE. The decrease in ACE activity by PRZ was correlated with its curative effect in infected mice. However, in experimentally induced pulmonary granulomata, the drug reduced granuloma size without affecting ACE activity of either serum or granuloma. It may be concluded that reduction in ACE activity may be beneficial as far as diminution of granuloma size is concerned and irrespective of whether there is an active infection or not. The possible use of Captopril as an antihypertensive in bilharzial infections associated with hypertension would probably not adversely affect the granulomatous lesions.

Relationship between schistosomicidal drug efficacy, gonadal steroid hormonal changes and state of disease immunopathology in murine schistosomiasis mansoni.

The schistosomicidal efficacy of praziquantel (2 x 500 mg/kg), oxamniquine (1 x 100 mg/kg) and combined one-third the curative dose of each of them (333 mg/kg praziquantel + 33 mg/kg oxamniquine), were correlated to gonadal steroid hormonal changes and state of disease immunopathology, in mice infected with 100 Schistosoma mansoni (S. mansoni) cercariae. Maximum efficacy recorded with combination regimen particularly 4 weeks after treatment, was accompanied by maximum reduction in granuloma volume (65%), least fall in testosterone level (-56.2 and -60.2% in male and female mice respectively) and increased progesterone level (+33.9 and +81.5% in male and female mice respectively). These findings revealed a potentiated effect of combination therapy on mature infection and the possible involvement of gonadal steroid hormones in affecting the efficacy of schistosomicidal drugs and state of disease immunopathology.

Effect of praziquantel versus hycanthone on deoxyribonucleic acid content of hepatocytes in murine schistosomiasis mansoni.

Cytophotometric measurement of the effect of praziquantel (500 mg/kg for 2 days) versus hycanthone (60 mg/kg for 3 days) on hepatocyte nuclear deoxyribonucleic acid (DNA) content was evaluated in Schistosoma mansoni infected mice. Drugs were given 8 weeks post-infection and repeated weekly for 4 weeks. DNA values of infected untreated control and infected drug treated groups were related to the median and upper diploid DNA values of normal control. Schistosoma mansoni infection per se did not change the hepatocyte DNA content, yet aneuploidy was 16.7%. Praziquantel did not result in significant change of DNA content or ploidy, while hycanthone resulted in marked significant increase of DNA content (328.9%) and aneuploidy (100%), compared to infected untreated control. Histopathological examination revealed hyperchromatic nuclei with mitosis in the hepatocytes of hycanthone treated mice, but not in praziquantel treated animals. These DNA changes were found to correlate with the reported safety of praziquantel and the carcinogenicity of hycanthone.

Effect of schistosomiasis infection on the clearance of phenazone in mice.

The disposition phenazone (antipyrine) was used to study the effect of Schistosoma mansoni infection on the activity of drug metabolizing enzymes in mice. Plasma elimination rate constant (Ke), elimination half-life (t1/2e), clearance (CL) and apparent volume of distribution (Vd) were estimated 8 and 12 weeks after infection of mice with 80 S. mansoni cercariae. Liver and kidney function tests were performed simultaneously. Infection increased the levels of glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactic dehydrogenase (LDH), alkaline phosphatase (AP) and total proteins 8 and 12 weeks post infection. At the same time a decrease was recorded in the total cholesterol level. Moreover infection with S. mansoni produced a decrease in phenazone clearance with an increase in the area under the curve (AUC) of the drug 8 and 12 weeks post infection. Elimination half-lives were 57.92 +/- 14.10 and 72.72 +/- 4.14 min 8 and 12 weeks after infection, respectively, compared to 19.29 +/- 3.30 and 26.14 +/- 5.31 min in corresponding controls. No statistically significant change was recorded in the volume of distribution of phenazone in the groups studied. In addition no significant correlation was found between parameters of phenazone disposition and the enzyme levels studied 8 and 12 weeks after infection.

Effect of specific chemotherapy on the immune response and resistance to reinfection in experimental Schistosomiasis mansoni.

Mice infected for 45 days with 120 Schistosoma mansoni cercariae and treated with praziquantel in a dose of 500 mg/kg for two consecutive days had a significant lower resistance to reinfection when challenged two weeks after treatment (45% compared to 88% in infected challenged untreated mice). In praziquantel-treated mice, the reduction in the per cent resistance was accompanied by a diminution in the size of hepatic granulomata and its in vivo correlate the delayed foot pad swelling. Moreover, the granuloma proportionate T-cell subset enumeration revealed a significant reduction in the number of T-helper cells. The humoral immune response as measured by the immediate foot pad swelling was not affected by praziquantel. Results reveal besides the diminution of the state in resistance to reinfection after praziquantel, possible involvement of egg-related pathology as a T-cell mediated reaction and as a mechanical obstacle in maintenance of this resistance.

Levamisole restored the compromised state of immunity after specific chemotherapy in experimental schistosomiasis mansoni.

Mice infected for 45 days with 120 Schistosoma mansoni cercariae and treated with levamisole (25 mg/kg subcutaneously) have more efficient acquired immunity when challenged with 240 Schistosoma mansoni cercariae the same day of treatment (97.7% # 87.7% in infected challenged controls). In praziquantel-treated mice (500 mg/kg for 2 days orally), the reduction in the percent resistance (45.5%) was accompanied by a significant diminution in the size of granuloma, delayed foot pad swelling and granuloma proportionate T-helper cells number. Levamisole when given two weeks post praziquantel treatment and with the challenge infection increased the percent resistance to 79.2%. The increase in percent resistance recorded in mice receiving both praziquantel and levamisole was accompanied by restoration of granuloma size, delayed foot pad swelling and granuloma proportionate T-helper cells number to infected challenged untreated control values. Results reveal-beside efficacy of levamisole as immunoregulant in schistosome immunity--a possible role for the granuloma as a T-cell mediated response in maintenance of immunity.

Effect of praziquantel on hepatic fibrosis in experimental Schistosomiasis mansoni.

The effect of specific chemotherapy on hepatic fibrosis was studied in Swiss albino mice infected with Schistosoma mansoni. The effect of treatment with praziquantel at 8, 12, and 20 weeks postinfection on fibrosis was assessed by determination of total hepatic collagen content, ratio of type III/I + III collagen, granuloma volume, and histopathological examination of liver section. Total collagen content was reduced in mice treated at the 8th week of infection compared to respective infected controls. The ratio of type III/I collagen was within normal limits. The decrease in collagen deposition was not observed when treatment was given 12 or 20 weeks postinfection. Early specific treatment of schistosomiasis may be important in the therapeutic approach to the control of morbidity in schistosomiasis.

Comparative effect of tiaprofenic acid and piroxicam alone and as adjuvants to antibilharzial therapy on pulmonary granuloma in unsensitized mice.

Granulomata formed in the liver or lung of man and animals infected with schistosomiasis are common manifestation of an inflammatory delayed hypersensitivity reaction. Non-steroidal anti-inflammatory drugs (NSAIDs) (tiaprofenic acid and piroxicam) have been used alone and as adjuvants to praziquantel in treating pulmonary granulomata induced in mice by injecting them intravenously with S. mansoni eggs. The size of the granulomata, as well as some immunological parameters, have been measured at the end of treatment. Both anti-inflammatory drugs effectively reduced the size of lung granulomata in a dose-dependent manner. The immediate skin reaction and, to a lesser extent, the delayed reaction were reduced by these drugs. Tiaprofenic acid, but not piroxicam, reduced the percent macrophage migration inhibition in vitro. The combined therapy of either of the drugs with praziquantel did not result in an additive effect.