Copper,zinc, and selenium in whole blood and thyroid tissue of people with various thyroid diseases

We investigated the possible differences among the concentrations of copper, zinc, and selenium, and their mutual relations in the whole blood and thyroid tissue of patients with various thyroid disorders. Trace elements were determined by total-reflection X-ray fluorescence. The mean levels of these metals in blood as well as the mean Cu/Zn, Cu/Se, and Zn/Se ratios in the patients with thyroid cancer were significantly higher that in other patients and the control groups. However, the mean Zn and Se concentrations in the thyroid cancer tissue were significantly lower than in the thyroid tissue of other patients. In addition, the mean Cu/Zn and Cu/Se ratios in the thyroid cancer tissue were significantly higher than in the patients with other thyroid diseases. We confirm that the highest levels of copper and zinc as well as the Cu/Zn, Cu/Se, and Zn/Se ratios in the whole blood of the patients with thyroid cancer may suggest the progression of the proliferation process in the thyroid gland. We suggest that the low concentrations of zinc and selenium in the thyroid tissue confirm their participation in the carcinogenic process.     

Maternal-fetal status of copper, iron, molybdenum, selenium, and zinc in obese pregnant women in late gestation

Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Further, obese women are more prone to have babies born with congenital abnormalities. Paucity of data on maternal-fetal disposition of essential trace elements in obese pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous samples were collected from obese patients (body mass index >30) and control pregnant women (body mass index <25) at time of spontaneous delivery or cesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se, and Zn determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and total antioxidant activity in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-fetal disposition and exchange parameters of elements studied were assessed using established critieria. Concentrations of Cu, Fe, Mo, Se, and Zn in the serum of control pregnant women at time of delivery averaged 2232.6, 2398.1, 10.9, 108.9, and 661.9 μg/L, respectively, whereas in the obese group, the values of the above elements averaged 2150.3, 2446.8, 12.6, 96.8, and 838.9 μg/L, respectively. Umbilical vein/maternal vein ratios of Cu, Fe, Mo, Se, and Zn in the control group averaged 0.29, 1.93, 1.06, 0.76, and 1.12, respectively, whereas in the obese group, their fetal-maternal ratios averaged 0.32, 2.23, 1.06, 0.78, and 1.53, respectively. The Cu:Zn ratio in the maternal vein of the obese group (3.60±0.20) was significantly lower (Student's t-test; p<0.05) than that of the controls (2.50±0.19); however, Cu:Fe ratio (1.04±0.08 vs 1.02±0.09) was not significantly different (Student's t-test; p>0.05) in the two groups. Varying differences were noted in the case of antioxidant enzyme activities between the control and study groups. We conclude that obesity is associated with alterations in maternal-fetal disposition of some essential trace elements and antioxidant enzyme status and that these alterations could pose a potential health risk for the mother as well as the fetus.     

Serum selenium levels and oxidative balance as differential markers in hepatic damage caused by alcohol

Aims

Antioxidant system abnormalities have been associated with ethanol consumption. This study examines the effects of chronic ethanol consumption on oxidative balance, including selenium (Se) levels in alcoholic patients with or without liver disease, and if these measurements could be indicative of liver disease.

Main methods

Serum Se levels, antioxidant enzymes' activities, malondialdehyde (MDA) and protein carbonyl (PC) were determined in three groups of patients: alcoholics without liver disease, alcoholics with liver disease, and non-alcoholics with liver disease; and in healthy volunteers.

Key findings

Serum Se levels were lower in alcoholic patients and in patients affected by liver disease and especially lower in the alcoholic liver disease group. These values were correlated with the activity of glutathione peroxidase (GPx), the antioxidant selenoprotein. The antioxidant activities of the glutathione reductase (GR) and superoxide dismutase (SOD) were also lower in the three non-healthy groups. However, GR activity decreased and SOD activity increased in the non-alcoholic liver disease group versus alcoholic groups. Higher concentrations of PC in serum were found in non-healthy groups and were higher in alcoholic patients who also showed higher MDA levels. The highest MDA and PC levels were found in the alcoholic liver disease group.

Significance

We conclude that serum Se levels are drastically decreased in alcoholic liver disease patients, showing that this element has a direct correlation with GPx activity, and lipid oxidation, suggesting that the serum Se/MDA ratio could be an indicator of hepatic damage caused by alcohol consumption, and pointing to Se as a possible antioxidant therapy.     

On the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm

Abstract

Background

Abdominal aortic aneurysm (AAA) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of AAA. However, only few studies have been conducted to evaluate the blood oxidative stress status of AAA patients.

Methods and results

Twenty seven AAA patients (mean age of 70 years) divided into two groups according to AAA size (≤50 or >50 mm) were compared with an age-matched group of 18 healthy subjects. Antioxidants (vitamins C and E, β-carotene, glutathione, thiols, and ubiquinone), trace elements (selenium, copper, zinc, and copper/zinc ratio) and markers of oxidative damage to lipids (lipid peroxides, antibodies against oxidized patients, and isoprostanes) were measured in each subject. The comparison of the three groups by ordinal logistic regression showed a significant decrease of the plasma levels of vitamin C (P = 0.011), α-tocopherol (P = 0.016) but not when corrected for cholesterol values, β-carotene (P = 0.0096), ubiquinone (P = 0.014), zinc (P = 0.0035), and of selenium (P = 0.0038), as AAA size increased. By contrast, specific markers of lipid peroxidation such as the Cu/Zn ratio (P = 0.046) and to a lesser extent isoprostanes (P = 0.052) increased.

Conclusion

The present study emphasizes the potential role of the oxidative stress in AAA disease and suggests that an antioxidant therapy could be of interest to delay AAA progression.     

Distribution of iron, cobalt, zinc and selenium in macrofungi

Samples of wild growing ectomycorrhizal and terrestrial saprobic macrofungi (mushrooms) were collected from unpolluted areas and analyzed for their iron, cobalt, zinc and selenium content. Trace elements were determined using long-term instrumental neutron activation analysis. In total, 217 samples, including 87 species of ectomycorrhizal fungi and 43 species of terrestrial saprobes, were examined. Distribution of trace element contents in ectomycorrhizal and saprobic macrofungi was investigated; results are thoroughly compared with previously published data. Doubtful literature data and ability of macrofungi to accumulate/concentrate investigated elements are discussed. Hygrophoropsis aurantiaca was found to concentrate Fe and Russula atropurpurea was confirmed as an effective Zn-accumulating species. Distribution of Se in ectomycorrhizal species was obviously different from that in saprobic species; selenium contents were higher in saprobic species (mostly above 2 ppm).     

Peroxisomes, oxidative stress, and inflammation

Peroxisomes are intracellular organelles mediating a wide variety of biosynthetic and biodegradative reactions.Included among these are the metabolism of hydrogen peroxide and other reactive species,molecules whose levels help define the oxidative state of cells.Loss of oxidative equilibrium in cells of tissues and organs potentiates inflammatory responses which can ultimately trigger human disease.The goal of this article is to review evidence for connections between peroxisome function,oxidative stress,and inflammation in the context of human health and degenerative disease.Dysregulated points in this nexus are identified and potential remedial approaches are presented.     

Relationship among carotenoid production,copper bioremediation and oxidative stress in Rhodotorula mucilaginosa RCL-11

Rhodotorula mucilaginosa RCL-11, a pigmented yeast isolated from a filter plant of a copper mine in the province of Tucumán, Argentina, supports high concentrations of the heavy metal Cu(II). Copper overload augmented carotenoid biosynthesis in this yeast, modifying at the same time the relative proportion of the pigments produced. Inhibition of the synthesis pathway with diphenylamine suggests an inverse relationship between carotenoid and copper biosorption by R. mucilaginosa RCL-11. The increased activity of superoxide dismutase and catalase measured under inhibition of carotenoid biosynthesis could explain these observations. Exposure to H₂O₂, a second oxidative stress agent, alone or in combination with Cu(II) also modified the carotenoid content, both qualitatively and quantitatively. The change in the relative proportion of the carotenoids torularhodin, torulene and beta-carotena, as well as the detection of gamma-carotene in the presence of H₂O₂ and Cu(II) allows to hypothesize that the carotenoids produced by R. mucilaginosa RCL-11 plays different roles in the oxidative stress response of this yeast.     

Urinary oxidative stress markers in children with autism

Abstract

Oxidative stress caused by increased production of free radicals and impaired functions of antioxidants remains as the major factor associated with the pathophysiology of many neuropsychiatric diseases.

Objective

The objective of the present study was to analyze the oxidative stress markers in urine sample since the collection of blood from these children is highly meticulous and also to evaluate whether these urinary markers can be correlated with the severity of autism.

Methods

The subjects of the study were 45 autistic children with different grades of severity (low functioning autism (LFA), medium functioning autism (MFA), and high functioning autism (HFA) according to Childhood Autism Rating Scale (CARS), n = 15 children in each group and 50 healthy children (age and sex matched). The boys and girls ratio involved in this study was 4:1, and they were of age 4–12 years. We determined the urinary levels of oxidative stress markers like thiobarbituric acid-reacting substances, lipid hydroperoxides, 4-hydroxy nonenal, protein carbonyls, sulfhydryl groups, total antioxidant capacity, total peroxide content, oxidative stress index, and also UA/Cr ratio in autistic children.

Results

The study observed a significant elevation in the level of oxidative stress markers in autistic children when compared with normal children. The level of antioxidants excreted in urine was found to be significantly low in autistic children. These findings when correlated with the degrees of severity, oxidative stress markers showed positive correlation with increasing order of severity (LFA > MFA > HFA), whereas antioxidants showed negative correlation.

Discussion

The study reveals that the urinary levels of oxidative stress markers can be considered as the measure of oxidative stress index in autistic children. The significant correlation between the severity of autism with urinary lipid peroxidation products also support the use of oxidative stress markers and antioxidants as biomarkers of autism.     

Vanadium distribution, lipid peroxidation and oxidative stress markers upon decavanadate in vivo administration

The contribution of decameric vanadate species to vanadate toxic effects in cardiac muscle was studied following an intravenous administration of a decavanadate solution (1mM total vanadium) in Sparus aurata. Although decameric vanadate is unstable in the assay medium, it decomposes with a half-life time of 16 allowing studying its effects not only in vitro but also in vivo. After 1, 6 and 12h upon decavanadate administration the increase of vanadium in blood plasma, red blood cells and in cardiac mitochondria and cytosol is not affected in comparison to the administration of a metavanadate solution containing labile oxovanadates. Cardiac tissue lipid peroxidation increases up to 20%, 1, 6 and 12h after metavanadate administration, whilst for decavanadate no effects were observed except 1h after treatment (+20%). Metavanadate administration clearly differs from decavanadate by enhancing, 12h after exposure, mitochondrial superoxide dismutase (SOD) activity (+115%) and not affecting catalase (CAT) activity whereas decavanadate increases SOD activity by 20% and decreases (-55%) mitochondrial CAT activity. At early times of exposure, 1 and 6h, the only effect observed upon decavanadate administration was the increase by 20% of SOD activity. In conclusion, decavanadate has a different response pattern of lipid peroxidation and oxidative stress markers, in spite of the same vanadium distribution in cardiac cells observed after decavanadate and metavanadate administration. It is suggested that once formed decameric vanadate species has a different reactivity than vanadate, thus, pointing out that the differential contribution of vanadium oligomers should be taken into account to rationalize in vivo vanadate toxicity.     

Limited effects of combined dietary copper deficiency/iron overload on oxidative stress parameters in rat liver and plasma

Copper (Cu) deficiency decreases the activity of Cu-dependent antioxidant enzymes such as Cu,zinc-superoxide dismutase (Cu,Zn-SOD) and may be associated with increased susceptibility to oxidative stress. Iron (Fe) overload represents a dietary oxidative stress relevant to overuse of Fe-containing supplements and to hereditary hemochromatosis. In a study to investigate oxidative stress interactions of dietary Cu deficiency with Fe overload, weanling male Long–Evans rats were fed one of four sucrose-based modified AIN-93G diets formulated to differ in Cu (adequate 6 mg/kg diet vs. deficient 0.5 mg/kg) and Fe (adequate 35 mg/kg vs. overloaded 1500 mg/kg) in a 2×2 factorial design for 4 weeks prior to necropsy. Care was taken to minimize oxidation of the diets prior to feeding to the rats. Liver and plasma Cu content and liver Cu,Zn-SOD activity declined with Cu deficiency and liver Fe increased with Fe overload, confirming the experimental dietary model. Liver thiobarbituric acid reactive substances were significantly elevated with Fe overload (pooled across Cu treatments, 0.80±0.14 vs. 0.54±0.08 nmol/mg protein; P<.0001) and not affected by Cu deficiency. Liver cytosolic protein carbonyl content and the concentrations of several oxidized cholesterol species in liver tissue did not change with these dietary treatments. Plasma protein carbonyl content decreased in Cu-deficient rats and was not influenced by dietary Fe overload. The various substrates (lipid, protein and cholesterol) appeared to differ in their susceptibility to the in vivo oxidative stress induced by dietary Fe overload, but these differences were not exacerbated by Cu deficiency.     

Leukocyte selenium, zinc, and copper concentrations in preeclamptic and normotensive pregnant women

Preeclampsia is an important cause of maternal and perinatal mortality worldwide. The etiology of this relatively common medical complication of pregnancy, however, remains unknown. We studied the relationship between maternal leukocyte selenium, zinc, and copper concentrations and the risk of preeclampsia in a large hospital-based case-control study. One hundred seventy-one women with proteinuric pregnancy-induced hypertension (with or without seizures) comprised the case group. Controls were 184 normotensive pregnant women. Leukocytes were separated from blood samples collected during the patients’ postpartum labor and delivery admission. Leukocyte concentrations for the three cations were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Concentrations for each cation were reported as micrograms per gram of total protein. Women with preeclampsia had significantly higher median leukocyte selenium concentrations than normotensive controls (3.23 vs 2.80 μg/g total protein, p<0.0001). Median leukocyte zinc concentrations were 31% higher in preeclamptics as compared with controls (179.15 vs 136.44 μg/g total protein, p<0.0001). Although median leukocyte copper concentrations were slightly higher for cases than controls, this difference did not reach statistical significance (17.72 vs 17.00 μg/g total protein, p=0.468). There was evidence of a linear increase in risk of preeclampsia with increasing concentrations of selenium and zinc. The relative risk for preeclampsia was 3.38 (adjusted odds ratio [OR]=3.38, 95% confidence interval [CI]=1.53–7.54) among women in the highest quartile of the control selenium distribution compared with women in the lowest quartile. The corresponding relative risk and 95% CI for preeclampsia was 5.30 (2.45–11.44) for women in the highest quartile of the control zinc distribution compared with women in the lowest quartile. There was no clear pattern of a linear trend in risk with increasing concentration of leukocyte copper concentrations (adjusted for linear trend in risk =0.299). Our results are consistent with some previous reports. Prospective studies are needed to determine whether observed alterations in selenium and zinc concentrations precede preeclampsia or whether the differences may be attributed to preeclampsia-related alterations in maternal and fetal-placental trace metal metabolism.     

Association between interleukin 4 gene intron 3 VNTR polymorphism and recurrent aphthous stomatitis in a cohort of Turkish patients

Objective

Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases, with a multifactorial etiopathogenesis, an interaction between predisposing factors and/or systemic conditions and immunological components in genetically predisposed subjects. Although there is no clear genetic mode of inheritance, there is evidence that inheritance of specific gene polymorphisms may predispose individuals to RAS. The purpose of the present study was to investigate a possible association between the functional interleukin 4 (IL4) VNTR genetic polymorphism and RAS in a sample of Turkish patients.

Methods

The study included 145 unrelated patients with a clinical diagnosis of RAS and 150 unrelated healthy controls. Genomic DNA was isolated and IL4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers.

Results

The distribution of genotype and allele frequencies of IL4 gene intron 3 VNTR polymorphism was statistically different between RAS patients and control group (p < 0.0001 and p < 0.0001, respectively) P2P2 genotype and P2 allele were also found to be protective with a lower risk for susceptibility to RAS (p < 0.0001).

Conclusion

The results of this study suggest that intron 3 VNTR polymorphism in the IL4 gene is associated with RAS susceptibility in Turkish population.     

Oxidative and nitrative stress markers in glaucoma

Glaucoma is a progressive optic neuropathy and is the leading cause of blindness in the United States and other industrialized countries. Elevated pressure in the eye is a risk factor for glaucoma and indeed experimental studies of induced pressure elevation in nonhuman primate's results in typical glaucomatous optic nerve damage. However, normal intraocular pressure can also lead to loss of vision in glaucoma. Although the initiating causes leading to glaucoma are unknown, oxidative and nitrative stress appears to play a role in the progressive neuronal death that is characteristic of glaucomatous optic nerve damage. Increased markers of oxidative stress that have been reported in glaucoma include protein nitrotyrosine, carbonyls in proteins, lipid oxidation products and oxidized DNA bases. Studies have also highlighted the role of nitric oxide in glaucoma by reporting the presence of inducible nitric oxide synthase in the iris-ciliary body, retina and in the glaucomatous optic nerve head of experimental rat models. This review discusses the role of reactive oxygen and nitrogen species in the pathogenesis of glaucoma and examines the relevance of antioxidants in neurodegeneration associated with the disease. It is concluded that oxidative and nitrative stress have a pathogenic role in glaucoma.     

Mitochondria,oxidative stress and cell death

In addition to the well-established role of the mitochondria in energy metabolism, regulation of cell death has recently emerged as a second major function of these organelles. This, in turn, seems to be intimately linked to their role as the major intracellular source of reactive oxygen species (ROS), which are mainly generated at Complex I and III of the respiratory chain. Excessive ROS production can lead to oxidation of macromolecules and has been implicated in mtDNA mutations, ageing, and cell death. Mitochondria-generated ROS play an important role in the release of cytochrome c and other pro-apoptotic proteins, which can trigger caspase activation and apoptosis. Cytochrome c release occurs by a two-step process that is initiated by the dissociation of the hemoprotein from its binding to cardiolipin, which anchors it to the inner mitochondrial membrane. Oxidation of cardiolipin reduces cytochrome c binding and results in an increased level of “free” cytochrome c in the intermembrane space. Conversely, mitochondrial antioxidant enzymes protect from apoptosis. Hence, there is accumulating evidence supporting a direct link between mitochondria, oxidative stress and cell death.     

Relation between oxidative stress markers and antioxidant endogenous defences during exhaustive exercise

Hydrogen peroxide (H₂O₂) could induce oxidative damage at long distance from its generation site and it is also an important signalling molecule that induces some genes related to oxidative stress. Our objective was to study the plasma and blood cells capability to detoxify H₂O₂ after intense exercise and its correlation with oxidative damage. Blood samples were taken from nine professional cycling, participating in a mountain stage, under basal conditions and 3 h after the competition. Catalase and glutathione peroxidase activities decreased (40 and 50% respectively) in neutrophils after the cycling stage, while glutathione peroxidase increased (87%) in lymphocytes. Catalase protein levels and catalase specific activity maintained basal values after the stage in plasma. Catalase protein levels decreased (48%) in neutrophils and its specific activity increased up to plasma values after exercise. Myeloperoxidase (MPO) increased (39%) in neutrophils after the cycling stage. Exercise-induced hemolysis and lymphopenia inversely correlated with cellular markers of oxidative stress. Plasma malondialdehyde (MDA) directly correlated with neutrophil MPO activity and erythrocytes MDA. Intense exercise induces oxidative damage in blood cells as erythrocytes and lymphocytes, but not in neutrophils.     

Relation between oxidative stress markers and antioxidant endogenous defences during exhaustive exercise

Hydrogen peroxide (H₂O₂) could induce oxidative damage at long distance from its generation site and it is also an important signalling molecule that induces some genes related to oxidative stress. Our objective was to study the plasma and blood cells capability to detoxify H₂O₂ after intense exercise and its correlation with oxidative damage. Blood samples were taken from nine professional cycling, participating in a mountain stage, under basal conditions and 3 h after the competition. Catalase and glutathione peroxidase activities decreased (40 and 50% respectively) in neutrophils after the cycling stage, while glutathione peroxidase increased (87%) in lymphocytes. Catalase protein levels and catalase specific activity maintained basal values after the stage in plasma. Catalase protein levels decreased (48%) in neutrophils and its specific activity increased up to plasma values after exercise. Myeloperoxidase (MPO) increased (39%) in neutrophils after the cycling stage. Exercise-induced hemolysis and lymphopenia inversely correlated with cellular markers of oxidative stress. Plasma malondialdehyde (MDA) directly correlated with neutrophil MPO activity and erythrocytes MDA. Intense exercise induces oxidative damage in blood cells as erythrocytes and lymphocytes, but not in neutrophils.     

Cellular and biochemical parameters of exercise-induced oxidative stress: relationship with training levels

To better clarify the relationship between physical activity and oxidative stress, we determined the effects of a maximal test in 18 young subjects with different training levels (six professional Athletes and 12 non-agonists (NA)). Redox homeostasis (total antioxidant activity (TAS), vitamin C and glutathione (GSH)), oxidative damage (diene conjugation and hemolysis), lymphocyte cell death and repair systems (apoptosis, micronuclei and Hsp70 expression) were evaluated. We found that agonistic training led to a chronic oxidative insult (high baseline values of oxidized glutathione (GSSG), micronuclei and hemolysis). On the contrary, NA with the lowest level of training frequency showed a well balanced profile at rest, but they were more susceptible to exercise-induced variations (GSSG/GSH and diene increased values), respect to the NA with an higher level of training. As almost all the parameters employed in this study showed inter-individual variations, the GSSG/GSH ratio remains the most sensitive and reliable marker of oxidative stress, accordingly with other data just reported in the literature.     

Amelioration of age-dependent increase in oxidative stress markers in male mice by extract of Potentilla fulgens

Objective: To investigate the effect of Potentilla fulgens extract on lipid peroxidation and antioxidant status in male mice as a function of age.

Methods: Eighteen-month-old Swiss albino male mice were administered the dichloromethane-methanol extract of P. fulgens (250?mg/kg b.w.) on alternate days via intraperitoneal route for a period of 14 days. Lipid peroxidation and activities of catalase (CAT) and glutathione peroxidase (GPx1) in liver and kidney were measured and serum oxygen radical absorbance capacity (ORAC) assay was estimated. Phytochemical analysis of P. fulgens extract using high performance thin layer chromatography (HPTLC) was carried out with gallic acid, quercetin, catechin, and epicatechin as markers.

Results: Significant increase in level of thiobarbituric acid-reactive substances (TBARS), decreased GPx1, and CAT activities as well as reduction in ORAC were observed in 18-month-old mice as compared to that of 2-month-old mice. Treatment with P. fulgens extract significantly lowered TBARS level, ameliorated CAT, and GPx1 activities in liver and kidney and improved serum ORAC in aging mice. HPTLC studies revealed well resolved bands of P. fulgens extract containing epicatechin and catechin.

Discussion: This study showed that P. fulgens is a potent antioxidative agent, which can emerge as a promising candidate in alleviating the age-associated oxidative stress and related diseases.     

Changes in serum selenium, copper, zinc levels and Cu/Zn ratio in patients with pulmonary tuberculosis during therapy

The effectiveness and success of antituberculosis therapy is mainly measured by its ability to identify the organism in the sputum. In certain cases, available tuberculosis tests are not satisfactory and do not provide enough information on the effectiveness of antituberculosis therapy. Copper (Cu), zinc (Zn), and selenium (Se) are the essential elements that play a crucial role in the immune system. The serum levels of these elements vary in many diseases including tuberculosis. In this study, we investigate whether the serum levels of Cu, Zn, and Se change during antituberculosis therapy. We have included 22 pulmonary tuberculosis cases that were newly diagnosed with positive sputum and 18 healthy subjects. At the beginning and 2 mo after therapy, serum levels of Cu, Zn, and Se were measured by atomic absorption spectrometry. Despite Se and Cu levels not being affected during the treatment, we found that there was a significant increase in the levels of Zn and a decrease in the Cu/Zn ratio. Serum Zn levels and the Cu/Zn ratio could be used as a valuable laboratory tool for the clinicians to assess response to therapy or effectiveness of the ongoing antituberculosis therapy.