Comparison among ACR1997, SLICC and the new EULAR/ACR classification criteria in childhood-onset systemic lupus erythematosus

Abstract Background: To date there are no specific classification criteria for childhood-onset systemic lupus erythematosus (cSLE). This study aims to compare the performance among the American College of Rheumatology (ACR) 1997, the Systemic Lupus International Collaborating Clinics criteria (SLICC) and the new European League Against Rheumatism (EULAR)/ACR criteria, in a cSLE cohort. Methods: We conducted a medical chart review study of cSLE cases and controls with defined rheumatic diseases, both ANA positive, to establish each ACR1997, SLICC and EULAR/ACR criterion fulfilled, at first visit and 1-year-follow-up. Results: Study population included 122 cSLE cases and 89 controls. At first visit, SLICC criteria had higher sensitivity than ACR 1997 (89.3% versus 70.5%, p < 0.001), but similar specificity (80.9% versus 83.2%, p = 0.791), however performance was not statistically different at 1-year-follow-up. SLICC better scored in specificity compared to EULAR/ACR score ≥ 10 at first visit (80.9% versus 67.4%, p = 0.008) and at 1-year (76.4% versus 58.4%, p = 0.001), although sensitivities were similar. EULAR/ACR criteria score ≥ 10 exhibited higher sensitivity than ACR 1997 (87.7% versus 70.5%, p < 0.001) at first visit, but comparable at 1-year, whereas specificity was lower at first visit (67.4% versus 83.2%, p = 0.004) and 1-year (58.4% versus 76.4%, p = 0.002). A EULAR/ACR score ≥ 13 against a score ≥ 10, resulted in higher specificity, positive predictive value, and cut-off point accuracy. Compared to SLICC, a EULAR/ACR score ≥ 13 resulted in lower sensitivity at first visit (76.2% versus 89.3%, p < 0.001) and 1-year (91% versus 97.5%, p = 0.008), but similar specificities at both assessments. When compared to ACR 1997, a EULAR/ACR total score ≥ 13, resulted in no differences in sensitivity and specificity at both observation periods. Conclusions: In this cSLE population, SLICC criteria better scored at first visit and 1-year-follow-up. The adoption of a EULAR/ACR total score ≥ 13 in this study, against the initially proposed ≥10 score, was most appropriate to classify cSLE. Further studies are necessary to address if SLICC criteria might allow fulfillment of cSLE classification earlier in disease course and may be more inclusive of cSLE subjects for clinical studies.

Biological activity and redistribution of nucleolar proteins of two different cell lines treated with cis-dichloro-1,2-propylenediamine-N,N,N',N'-tetraacetato ruthenium (III) (RAP).

The interaction of a newly synthesized antitumor complex cis-dichloro-1,2-propylenediamine-N,N,N',N'-tetraacetato ruthenium (III) (RAP) with DNA was investigated in vitro through a number of techniques including comet assay, immunoprecipitation, and immunolocalization of certain nucleolar proteins (the upstream binding factor (UBF) and fibrillarin) involved in DNA transcription, rRNA processing, and ribosomal assembly. The results showed that RAP binds to the DNA of two cell lines (H4 and Hs-683) causing a delay in cell proliferation rate leading to a number of cellular modifications. These modifications include DNA-damage assessed by the single cell gel electrophoresis method (comet assay) and variation in the expression of nucleolar proteins; UBF was more abundant in RAP treated cells, this was explained by the high affinity of this protein to DNA modified by RAP. On the other hand, fibrillarin was found in less quantities in RAP treated cells which was explained by a de-regulation of the ribosomal machinery caused by RAP.

Pharmacokinetics of cefpodoxime proxetil with special reference to biochemical parameters, tissue residue, and spermatozoa motility in rats.

Background : Cefpodoxime is a semisynthetic third generation cephalosporin analogue with a relatively broader spectrum of antimicrobial activity against gram negative and gram positive organisms. This is attributed to their somewhat increased resistance to degradation by the betalactamase. Cefpodoxime shows good activity against Klebsiella pneumonia, many members of enterobactericeae and almost all strains of Escherichia coli. It is extensively used in human beings against infections caused by susceptible organisms for a prolonged period and even without its judicious indication. Though various researchers have worked on the pharmacokinetic aspects of the drug, its effects on biochemical parameters and spermatozoa activity are scarcely available in literature. Aim : To determine the oral kinetic ( blood and tissue) after single therapeutic dose of cefpodoxime proxetil (20mg/kg oral bid 7 days) in rats of either sex on tissue half life and certain biochemical parameters such as glucose, hemoglobin, protein, ALT, AST and other parameters like tissue residue, sperm count and spermatozoa motility in male rats. Materials and Methods : For kinetic studies,24 Wister rats of either sex, 3 months of age, (180-210 gm) were used.(Group I-IV; n=6) Blood samples collected from each animal of Group IV through heart puncture at 0 hour to serve as predrug control. All the group (I-IV) received cefpodoxime proxetil 20 mg/kg once orally as a single dose. At the end of 1,4,12 and 24 hour post oral administration, GroupI,II,III and IVwere utilized for kinetic studies. Blood samples were collected from each animal and vital organs viz brain, lung, liver, spleen, kidney and heart were dissected out for drug analysis and determination of weight. For biochemical parameters, tissue residue and spermatozoa motility, twelve male rats were randomly divided into Groups A and B (n=6) Group B received cefpodoxime (20mg/kg orally bid 7 days) while Group A served as control. Biochemical parameters [Blood glucose, protein, Aspartate transaminase(AST), Alanine transaminase(ALT)and hemoglobin] were measured at 0 and 7 th day while sperm count (total,live and dead)and mean organ weight (study and control group) and tissue residue of drug were evaluated at the end of treatment. Absorption of cefpodoxime was observed at 2 hour and reached a maximum at 4 hour and persisted in blood till 24 hour. Elimination half life in lung was highest followed by heart, liver, kidney and spleen while t½ k in plasma was very low suggesting more affinity of cefpodoxime for tissues than blood. Results and Conclusion : Blood glucose, protein, AST and ALT activities were not significantly altered but the hemoglobin level and total and live sperm count decreased significantly in the study group compared to the control group. Residual level of cefpodoxime was highest in liver followed by kidney and other study organs. Therefore, the drug should be used in human beings judiciously and further study on human subjects is warranted.

Effect of oral ingestion of an extract of the herb Uncaria tomentosa on the biodistribution of sodium pertechnetate in rats

The aim of the present study was to determine the effect of the oral ingestion of an extract of the herb Uncaria tomentosa (cat's claw) on the biodistribution of the radiobiocomplex sodium pertechnetate (Na99mTcO4) in rats. The animals (male Wistar rats, 2 months old, 180-220 g), were treated (1 mL) with an U. tomentosa extract (32 mg/mL, N = 5) or 0.9 percent NaCl solution (control, N = 5) for 7 days. After this period, Na99mTcO4 (3.7 MBq, 0.3 mL) was injected through the ocular plexus and after 10 min the rats were killed, the organs isolated and counted in a well-gamma counter. A significant (P < 0.05) alteration in Na99mTcO4 uptake i) from 0.57 ± 0.008 to 0.39 ± 0.06 percentATI/organ (P < 0.05) and from 0.57 ± 0.17 to 0.39 ± 0.14 percentATI/g (P < 0.05) was observed in the heart, ii) from 0.07 ± 0.02 to 0.19 ± 0.07 percentATI/g in the pancreas, and iii) from 0.07 ± 0.01 to 0.18 ± 0.07 percentATI/g (P < 0.05) in muscle after treatment with this extract. Although these results were obtained with animals, caution is advisable in the interpretation of the nuclear medicine examination when the patient is using this herb. This finding is probably an example of drug interaction with a radiopharmaceutical, a fact that could lead to misdiagnosis of the examination in clinical practice with unexpected consequences for the patient.

The ingestión of a Nectandra membran cea extract changes the bioavailability of technetium-99m radiobiocomplex in rat organs

The radiobiocomplexes labeled with technetium-99m (Tc-99m) have been widely used in nuclear medicine in single photon emission computed tomography and in basic research. The aim of this study was to assess the influence of a Nectandra membran cea extract on the bioavailability of the sodium pertechnetate (Na99mTc0(4)) radiobiocomplex in rat organs. The animals were treated with a N. membran cea extract (30 mg/ ml), for 6 days. Na99mTc0(4) was injected, the organs were isolated and weighed, and the radioactivity was determined in each organ ( percentATI/organ). The percentATI/organ was divided by the mass of each organ to calculate the percentATI/g. A significant increase of the percentATI/organ of Na99mTc0(4) was observed in muscle and thyroid as well as in the percentATI/g in the heart, kidney and thyroid. These findings could result from the interaction between components of the plant extract and the radiobiocomplex which may influence the uptake Na99mTc0(4) in rat organs. Therefore, precaution is suggested in the interpretation of nuclear medicine results in patients using this herb.

Tissue schizontocidal effect of trifluoroacetyl primaquine in Plasmodium yoelii infected mice and Plasmodium cynomolgi infected monkeys.

Trifluoroacetyl primaquine oxalate (M8506) was compared with primaquine phosphate for tissue schizontocidal action in rodent and simian malaria. In Plasmodium yoelii sporozoites infected mice, the causal prophylactic effects of M8506 at 5, 10 and 20 mg(base)/kg were 56.7%, 87.2% and 100%, respectively, comparable to those of primaquine (54.4%, 90.8% and 100%). In P. cynomolgi sporozoites infected rhesus monkeys 4 dosage regimens of the two agents were compared for radical curative effect. On the first day of treatment pyronaridine phosphate 10 mg(base)/kg twice a day were intramuscularly injected to eliminate erythrocytic stages of P. cynomolgi. At the dosage of 3.0 mg(base)/kg/day x 3, both M8506 and primaquine radically cured the monkeys. At 0.75 mg/kg/day x 3, 12 of 13 (92.3%) monkeys cured by M8506, 5 of 9 (55.6%) cured by primaquine. At 1.5 and 0.375 mg/kg/day x 3, the radical curative effects of M8506 were also better than those of primaquine. Since the toxicity of M8506 was significantly milder in mice, rats and dogs than that of primaquine, M8506 has potential as a tissue schizontocide.