A combination of semi-purified L-methioninase with tamoxifen citrate to ameliorate breast cancer in athymic nude mice.

BACKGROUND: Chemotherapy nonspecifically targets both tumor and healthy proliferating cells. Methionine deprivation using L-methioninase along with chemotherapy appears promising towards cancer management. The present study is an attempt to use a new combination of L-methioninase with Tamoxifen (TAM) to treat breast cancer in mice. METHODS AND RESULTS: L-Methioninase from Methylobacterium sp. was partially purified (SPMet's) by cold acetone precipitation and lyophilized. Its cytotoxicity effect, alone and in combination with Tamoxifen, was evaluated in vitro (MCF-7) cells and in vivo (athymic nude mice) conditions. SPMet's was found to inhibit the growth of MCF-7 cells with an IC50 value of 47.05 µg/ml, while the combination of SPMet's and TAM had an IC50 of 6.4 µg/ml. Athymic nude mice were grouped into: Group-I - Tumor control; Group-II - TAM; Group-III - SPMet's; Group-IV - SPMet's + TAM. Tumor growth inhibition (TGI) was maximum in Group-IV with 84.65% followed by Group-II with 65.12%. Hematological and Biochemical parameters in Group-II, III, and IV were restored to normal levels. Tumor histopathology showed increased apoptosis and necrosis in Group-IV. Caspases 3 & 8 gene upregulation was significantly higher in Group-IV than other treated groups, indicating higher efficacy of the combination approach. CONCLUSION: This is the first study report about a combination of SPMet's and TAM on in vivo breast cancer model, with significantly higher anticancer activity and without noticeable side effects. The findings of this study have several important implications for future clinical studies.

Clinical and Laboratory Profile of Macrophage Activation Syndrome in Kawasaki Disease: A Single Centre Cross-Sectional Study.

OBJECTIVE: To study the prevalence of Macrophage Activation Syndrome (MAS) in children with Kawasaki disease (KD) and to devise a classification tree for predicting MAS in early KD based on easily available clinical and laboratory information using artificial intelligence (AI) technology. METHODS: A prospective cross-sectional observational study was conducted (March 2020 - October 2021) during which hospitalized children aged 1-18 years with KD were consecutively enrolled. Those with positive RTPCR test or IgM/IgG serology for COVID-19 were excluded. The clinical and laboratory profiles of children with and without MAS were studied. A multivariable logistic regression (LR) model was developed utilizing backward elimination method to determine the relationship between select candidate predictor variables and MAS in patients with KD. A classification tree was created based on these using artificial intelligence algorithms. RESULTS: Sixty-two children were diagnosed with KD during the study period, of these, 42 children with KD were included; 14 (33.3 %) were diagnosed with MAS. The median (IQR) duration of fever (days) was significantly more in MAS than those without MAS [7 (5, 15) vs 5 (5, 9), P < 0.05]. Serum albumin (g/dL) was significantly lower in those with MAS [2.3 (2.2, 2.7) vs 2.8 (2.3, 3.1), P = 0.03]. The classification tree constructed by the AI-based algorithm predicted that in children with KD who had myocardial dysfunction, serum albumin ≤ 2.8 g/dL and fever > 6 days duration at admission had increased likelihood of developing MAS. In children without myocardial dysfunction, alanine transaminase (ALT) levels > 70 U/L and fever > 5 days were equally predictive of MAS. CONCLUSION: Nearly one-third of the children with KD had MAS. Clinicians should consider screening all children with KD for MAS at admission. A classification tree based on the presence of myocardial dysfunction, duration of fever > 6 days, ALT levels and hypoalbuminemia can identify MAS in the course of KD.

Comparison Between Use of Oral Misoprostol Versus Vaginal Misoprostol for Induction of Labour at Term.

BACKGROUND AND OBJECTIVE: In modern obstetrics, around 30% of cases require induction of labour for various reasons. Misoprostol is gaining popularity as pharmacological inducing agent, though the route and dosage of administration are not standardised. The objective of the study is to compare the safety and efficacy of the two routes of misoprostol administration-oral (100 µg 4th hourly) and vaginal (25 µg 4th hourly), for induction of labour at term. METHODS: In this randomised trial, 104 women having crossed the expected date of delivery without going into spontaneous labour and cases which had premature rupture of membranes <12 h were considered for labour induction and were divided into two equal groups. Group A received 100 µg misoprostol orally 4th hourly, and group B received 25 µg misoprostol vaginally 4th hourly. Labour characteristics and maternal and foetal outcome were compared. RESULTS: In terms of maternal outcome, mean number of doses for oral group is 2.73 and vaginal group is 3.04. In oral group, mean induction to vaginal delivery interval was 13 h 43 min and in vaginal group interval is 13 h 26 min which was statistically not significant. The need for oxytocin augmentation was also statistically not significant. Both groups had equal number of failed inductions. Emergency LSCS done for foetal distress was more in vaginal group 2.9% compared to oral group which is 1%, but difference was not statistically significant (p value -0.55). Number of thick MSL in oral group was 3.2% as compared to vaginal group which is 10.7% which was statistically significant (p value -0.04). APGAR score at 5 min 7/10 was seen in 7.7% in vaginal group as compared to 0% in oral group which was also statistically significant (0.004). Number of NICU admissions was also more in vaginal group compared to oral group. CONCLUSION: Misoprostol in either oral or vaginal route has proven to be equally effective for inducing labour in women at term pregnancy. However, occurrence of lesser incidence of meconium-stained liquor and NICU admissions and fewer caesareans with better neonatal outcome in women induced with oral misoprostol outweighs its advantages over the vaginal misoprostol.