Effects Of Metronidazole Treatment Research Articles

Resistance towards metronidazole in Blastocystis sp.: A pathogenic consequence.

Blastocsytis sp. is a protozoan parasite that has been linked to common gastrointestinal illnesses. Metronidazole, the first line therapy, was reported to show frequent inefficacy. Previously, Blastocystis sp. isolated from different population showed varying metronidazole resistance. However, the effect of metronidazole treatment on pathogenic potentials of Blastocystis sp. isolated from different populations, which is known to have different gut environment, is unclear. This study investigates the in vitro effect of metronidazole on the pathogenic potentials of Blastocystis sp. isolated from urban and orang asli individuals. Blastocystis sp. ST 3 isolated from symptomatic and asymptomatic individuals were treated with a range of metronidazole concentration. The parasites’ growth characteristics, apoptotic rate, specific protease activity and the ability to proliferate cancer cells were analyzed upon treatment with 0.001 mg/l metronidazole. The study demonstrates that Blastocystis sp. isolates showed increase in the parasite numbers especially the amoebic forms (only in urban isolates) after treating with metronidazole at the concentration of 0.001 mg/ml. High number of cells in post-treated isolates coincided with increase of apoptosis. There was a significant increase in cysteine protease of Blastocystis sp. isolates upon treatment despite the initial predominance of serine protease in asymptomatic isolates. Metronidazole resistant Blastocystis sp. also showed significant increase in cancer cell proliferation. Resistance to metronidazole did not show significant different influence on the pathogenicity between Blastocystis sp. isolated from urban and orang asli individual. However, an increase in parasite numbers, higher amoebic forms, cysteine protease and ability to proliferate cancer cells implicates a pathogenic role. The study provides evidence for the first time, the effect of metronidazole towards enhancing pathogenic potentials in Blastocystis sp. when isolated from different gut environment. This necessitates the need for reassessment of metronidazole treatment modalities.

Transcriptome Analysis of Chemically-Induced Sensory Neuron Ablation in Zebrafish

Peripheral glia are known to have a critical role in the initial response to axon damage and degeneration. However, little is known about the cellular responses of non-myelinating glia to nerve injury. In this study, we analyzed the transcriptomes of wild-type and mutant (lacking peripheral glia) zebrafish larvae that were treated with metronidazole. This treatment allowed us to conditionally and selectively ablate cranial sensory neurons whose axons are ensheathed only by non-myelinating glia. While transcripts representing over 27,000 genes were detected by RNAseq, only a small fraction (~1% of genes) were found to be differentially expressed in response to neuronal degeneration in either line at either 2 hrs or 5 hrs of metronidazole treatment. Analysis revealed that most expression changes (332 out of the total of 458 differentially expressed genes) occurred over a continuous period (from 2 to 5 hrs of metronidazole exposure), with a small number of genes showing changes limited to only the 2 hr (55 genes) or 5 hr (71 genes) time points. For genes with continuous alterations in expression, some of the most meaningful sets of enriched categories in the wild-type line were those involving the inflammatory TNF-alpha and IL6 signaling pathways, oxidoreductase activities and response to stress. Intriguingly, these changes were not observed in the mutant line. Indeed, cluster analysis indicated that the effects of metronidazole treatment on gene expression was heavily influenced by the presence or absence of glia, indicating that the peripheral non-myelinating glia play a significant role in the transcriptional response to sensory neuron degeneration. This is the first transcriptome study of metronidazole-induced neuronal death in zebrafish and the response of non-myelinating glia to sensory neuron degeneration. We believe this study provides important insight into the mechanisms by which non-myelinating glia react to neuronal death and degeneration in sensory circuits.

Serum cytokine changes in Turkish children infected with Giardia lamblia with and without allergy: Effect of metronidazole treatment

The present report is a case control study aimed to determine the levels of cytokines and other parameters in the sera of allergy-complicated and uncomplicated giardiasic children before and after metronidazole treatment. The study included a total of 126 subjects; 52 giardiasic children, 34 allergy-complicated giardiasis (36.9%) and 34 healthy controls, as well as six cases of giardiasis simultaneously infected with other parasites or bacterial pathogens. Serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, soluble IL-2 receptor (sIL-2R), IL-6, IL-8, nitric oxide (NO), and C-reactive protein (CRP) were determined. TNF-α and sIL-2R levels significantly increased in giardiasic cases. IL-1β, IL-6, IL-8, CRP, and NO levels increased only in the cases associated with allergy. All increased variables significantly decreased following metronidazole treatment and returned to normal levels. Metronidazole-treated patients became 100% parasite free. In conclusion, increased TNF-α and sIL-2R may be involved in pathogenesis of non-allergic giardiasis and probably Th1 type immune response seems to be predominant and this response may be protective rather than causative of the disease. Activation of the immune system takes place in giardiasis. It is broader and more intense in allergy-complicated giardiasis than that of uncomplicated cases, most probably due to non-invasive character of G. lamblia. Enhanced IgE production pointed to Th2-type immune response and confirms its association with allergy.

Influence of the Bacterial Flora of the Gut on Sulfur Amino Acid Degradation: A Study of Patients with Bacterial Overgrowth before and during Treatment with Oxytetracycline or Metronidazole

The urinary excretion of sulfur amino acids and their main degradation products was determined in 10 patients with bacterial overgrowth during treatment with oxytetracycline or metronidazole. A normal excretion of total sulfur and inorganic sulfate was found during treatment with both antibiotics, indicating a normal intake, uptake, and oxidation of sulfur amino acids to inorganic sulfate. Irrespective of type of antibiotic given, a normalization of the increased ester sulfate excretion was found, favoring the opinion that both the aerobic and anaerobic flora of the gut contribute to the formation of sulfate esters. The cystathioninuria found in patients with bacterial overgrowth was normalized only by treatment with metronidazole. Both antibiotics resulted in a reduced excretion of taurine and thiosulfate, but especially for thiosulfate, the effect of metronidazole treatment was more pronounced. The results suggest that the bacterial flora of the gut, such as anaerobes, may be of importance in the formation of thiosulfate in the human body.