Evaluation of clinical profiles, imaging findings and antituberculosis treatment outcome in granulomatous mastitis: An Indian scenario.

BACKGROUND: The management of choice for granulomatous mastitis (GM) has yet to be determined but few studies have demonstrated that anti-tubercular treatment (ATT) could be an effective alternative therapeutic option. Hence, the objective of the current study is to determine the clinical feature, radiological imaging findings, and histopathological examination results exhibited by GM and tuberculosis (TB)-proven GM as well as to evaluate the ATT clinical outcome in GM patients. METHODS: The study was performed on 68 GM patients who were referred to the department of pulmonology by the breast clinic (from January 2018 to August 2021). Study populations were categorized into two groups GM and TB-proven GM patients and all were prescribed with standard ATT regimen and were continuously followed up. SPSS version 25 was employed for statistical assessment. RESULTS: Our study showed that 6 patients from GM and 4 patients from the TB-proven GM group got relapsed. For patients who displayed partial remission, ATT treatment was started after assessing the side effects potential. 14.6% (n = 6) and 7.4% (n = 2) patients who initially demonstrated partial remission were also completely cured. ATT treatment curable rate was determined to be 90% (n = 37) and 81.5% (n = 22) for GM and TB-proven GM patients correspondingly. Therefore, the current study demonstrated nil significant differences between groups. CONCLUSION: The current study warrants that ATT therapy could be an effective and better treatment of choice for GM patients irrespective of their clinical condition.

Erucin, a new promising cancer chemopreventive agent from rocket salads, shows anti-proliferative activity on human lung carcinoma A549 cells.

Erucin (ER) is a dietary isothiocyanate present in cruciferous vegetables, such as rocket salads (Erucasativa Mill., Diplotaxis sp.), that has been recently considered a promising cancer chemopreventive phytochemical. Biological activity of ER was investigated on human lung adenocarcinoma A549 cells, analyzing its effects on molecular pathways involved in apoptosis and cell cycle arrest, such as PARP-1 cleavage, p53 and p21 protein expression. Our results show that ER affects the A549 cell proliferation, enhancing significantly p53 and p21 protein expression in a dose-dependent manner (p<0.001). PARP-1 cleavage occurs only after exposure to high concentrations of ER (50 microM), in accordance to previous studies showing similar bioactivity of other isothiocyanates (ITCs). Our study reports for the first time that the induction of p53, p21 and PARP-1 cleavage may participate in the anti-proliferative activity of ER in human lung adenocarcinoma A549 cells. Comparison of data with those obtained with the isothiocyanate sulforaphane (SF), structurally related to ER, underlines the strong relationship between structural analogy of ITCs and their biological activity. The ability of dietary compounds to modulate molecular mechanisms that affect cancer cell proliferation is certainly a key point of the cancer prevention potential by functional foods.

Seasonal variation in emergency referrals to a Surgical Assessment Unit.

OBJECTIVES: To identify any seasonal variation in the pattern of referrals to the Surgical Assessment Unit (SAU). METHODS: Admission data to the SAU were collected prospectively during two audit periods of 13 weeks each (winter 2004/2005 and summer 2005). The data were analysed comparing numbers of admissions over the two audit periods and variations in the presenting complaint. RESULTS: There were a significantly greater number of referrals to the SAU in the summer compared with winter (999 vs. 849, p = 0.026). Whilst there were no significant differences in the sex distribution of patients presenting with general surgical symptoms, a significantly greater proportion of male patients presented with urological symptoms. Additionally, a significantly greater proportion of patients presented in the summer with scrotal/testicular symptoms compared with the winter (13.9% vs. 8.5%, p = 0.02). There was no significant difference between the two periods in terms of other diagnoses. In both study periods, the SAU was busy during weekdays compared with weekends. Whilst most patients arrived in the SAU between 9 am and midnight a smaller but not insignificant number arrived outside of these hours. CONCLUSIONS: Summer compared with winter was a busy period for the SAU. This may be important in managing emergency surgical admissions. A significantly greater proportion of patients presented with scrotal/testicular symptoms during the summer, the reasons for which are unclear. The SAU diverts workload away from busy Accident & Emergency departments.

Molecular basis for chemoprevention by sulforaphane: a comprehensive review.

The consumption of cruciferous vegetables has long been associated with a reduced risk in the occurrence of cancer at various sites, including the prostate, lung, breast and colon. This protective effect is attributed to isothiocyanates present in these vegetables, and sulforaphane (SF), present in broccoli, is by far the most extensively studied to uncover the mechanisms behind this chemoprotection. The major mechanism by which SF protects cells was traditionally thought to be through Nrf2-mediated induction of phase 2 detoxification enzymes that elevate cell defense against oxidative damage and promote the removal of carcinogens. However, it is becoming clear that there are multiple mechanisms activated in response to SF, including suppression of cytochrome P450 enzymes, induction of apoptotic pathways, suppression of cell cycle progression, inhibition of angiogenesis and anti-inflammatory activity. Moreover, these mechanisms seem to have some degree of interaction to synergistically afford chemoprevention.

Development of isothiocyanate-enriched broccoli, and its enhanced ability to induce phase 2 detoxification enzymes in mammalian cells.

Broccoli florets contain low levels of 3-methylsuphinylpropyl and 4-methylsulphinylbutyl glucosinolates. Following tissue disruption, these glucosinolates are hydrolysed to the corresponding isothiocyanates (ITCs), which have been associated with anticarcinogenic activity through a number of physiological mechanisms including the induction of phase II detoxification enzymes and apoptosis. In this paper, we describe the development of ITC-enriched broccoli through the introgression of three small segments of the genome of Brassica villosa, a wild relative of broccoli, each containing a quantitative trait locus (QTL), into a broccoli genetic background, via marker-assisted selection and analysis of glucosinolates in the florets of backcross populations. Epistatic and heterotic effects of these QTLs are described. The ITC-enriched broccoli had 80-times the ability to induce quinone reductase (a standard assay of phase II induction potential) when compared to standard commercial broccoli, due both to an increase in the precursor glucosinolates and a greater conversion of these into ITCs.

7-Methylsulfinylheptyl and 8-methylsulfinyloctyl isothiocyanates from watercress are potent inducers of phase II enzymes.

Watercress is an exceptionally rich dietary source of beta-phenylethyl isothiocyanate (PEITC). This compound inhibits phase I enzymes, which are responsible for the activation of many carcinogens in animals, and induces phase II enzymes, which are associated with enhanced excretion of carcinogens. In this study, we show that watercress extracts are potent inducers of quinone reductase (QR) in murine hepatoma Hepa 1c1c7 cells, a widely adopted assay for measuring phase II enzyme induction. However, contrary to expectations, this induction was not associated with PEITC (which is rapidly lost to the atmosphere upon tissue disruption due to its volatility) or a naturally occurring PEITC-glutathione conjugate, but with 7-methylsulfinyheptyl and 8-methylsulfinyloctyl isothiocyanates (ITCs). While it was confirmed that PEITC does induce QR (5 microM required for a two-fold induction in QR), 7-methylsulfinyheptyl and 8-methylsulfinyloctyl ITCs were more potent inducers (0.2 microM and 0.5 microM, respectively, required for a two-fold induction in QR). Thus, while watercress contains three times more phenylethyl glucosinolate than methylsulfinylalkyl glucosinolates, ITCs derived from methylsulfinylalkyl glucosinolates may be more important phase II enzyme inducers than PEITC, having 10 - to 25-fold greater potency. Analysis of urine by liquid chromatography-mass spectroscopy (LC-MS) following consumption of watercress demonstrated the presence of N:-acetylcysteine conjugates of 7-methylsulfinylheptyl, 8-methylsulfinyloctyl ITCs and PEITC, indicating that these ITCs are taken up by the gut and metabolized in the body. Watercress may have exceptionally good anticarcinogenic potential, as it combines a potent inhibitor of phase I enzymes (PEITC) with at least three inducers of phase II enzymes (PEITC, 7-methylsulfinylheptyl ITC and 8-methylsulfinyloctyl ITC). The study also demonstrates the application of LC-MS for the detection of complex glucosinolate-derived metabolites in plant extracts and urine.

Glucosinolate genetics and the attraction of the aphid parasitoid Diaeretiella rapae to Brassica.

The control of insect pests using parasitoids and carnivores has been successfully applied in protected cropping systems, orchards and forestry. Their success in annual field crops has been more limited due largely to the difficulties of attracting and maintaining a sufficient density of parasitoids in the crop before the levls of the insect herbivores become economically damaging. Parasitoids are known to be attracted to host-plant volatiles; thus, manipulating the host-plant chemistry may provide a means of enhancing the attraction of parasitoids to their prey. In this study we describe the differential attraction of the braconid wasp Diaeretiella rapae to two near-isogenic lines of Brassica oleracea which differ in a gene which alters the chemical structure of the isothiocyanates which are emitted following tissue damage. We demonstrate that, by enhancing the production of but-3-enyl isothiocyanate in B. oleracea and Brassica napus (oilseed rape), we can increase the attraction of D. rapae to these plants under standard field conditions.

Selective increase of the potential anticarcinogen 4-methylsulphinylbutyl glucosinolate in broccoli.

The putative anticarcinogenic activity of Brassica vegetables has been associated with the presence of certain glucosinolates. 4-Methylsulphinylbutyl isothiocyanate (sulphoraphane), derived from the corresponding glucosinolate found in broccoli, has previously been identified as a potent inducer of the anticarcinogenic marker enzyme quinone reductase [NADP(H):quinone-acceptor oxidoreductase] in murine hepatoma Hepa 1c1c7 cells. We have therefore produced a broccoli hybrid with increased levels of this anticarcinogenic glucosinolate and tested the ability of extracts to induce quinone reductase. A 10-fold increase in the level of 4-methylsulphinylbutyl glucosinolate was obtained by crossing broccoli cultivars with selected wild taxa of the Brassica oleracea (chromosome number, n = 9) complex. Tissue from these hybrids exhibited a >100-fold increase in the ability to induce quinone reductase in Hepa 1c1c7 cells over broccoli cultivars, due to both an increase in 4-methylsulphinylbutyl glucosinolate content and increased percentage conversion to sulphoraphane.

Genetics of aliphatic glucosinolates. IV. Side-chain modification in Brassica oleracea.

The biochemical and genetical relationship between aliphatic glucosinolates which have methylthioalkyl, methylsulphinylalkyl and alkenyl side chains has not been resolved by biochemical studies. In this study, two hypothetical models are tested by the genetic analysis of a backcross population between Brassica drepanensis and B. atlantica. The results support one of the models in which 3-methylthiopropyl glucosinolate is sequentially converted to 3-methylsulphinylpropyl, and then to 2-propenyl glucosinolate, by the action of dominant alleles at two loci. RFLP mapping positioned both loci on the same linkage group homologous to the B. napus N19 linkage group. The implication of the results for the genetic manipulation of glucosinolates in Brassica to improve flavour and nutritional properties, and in order to investigate plant-insect interactions, is discussed.

QTL analysis of flowering time in Arabidopsis thaliana.

Quantitative trait loci (QTL) analyses based on restriction fragment length polymorphism maps have been used to resolve the genetic control of flowering time in a cross between two Arabidopsis thaliana ecotypes H51 and Landsberg erecta, differing widely in flowering time. Five quantitative trait loci affecting flowering time were identified in this cross (RLN1-5), four of which are located in regions containing mutations or loci previously identified as conferring a late-flowering phenotype. One of these loci is coincident with the FRI locus identified as the major determinant for late flowering and vernalization responsiveness in the Arabidopsis ecotype Stockholm. RLN5, which maps to the lower half of chromosome five (between markers mi69 and m233), only affected flowering time significantly under short day conditions following a vernalization period. The late-flowering phenotype of H51 compared to Landsberg erecta was due to alleles conferring late flowering at only two of the five loci. At the three other loci, H51 possessed alleles conferring early flowering in comparison to those of Landsberg erecta. Combinations of alleles conferring early and late flowering from both parents accounted for the transgressive segregation of flowering time observed within the F2 population. Three QTL, RLN1, RLN2 and RLN3 displayed significant genotype-by-environment interactions for flowering time. A significant interaction between alleles at RLN3 and RLN4 was detected.

RFLP mapping of quantitative trait loci controlling seed aliphatic-glucosinolate content in oilseed rape (Brassica napus L).

We report the RFLP mapping of quantitative trait loci (QTLs) which regulate the total seed aliphaticglucosinolate content in Brassica napus L. A population of 99 F1-derived doubled-haploid (DH) recombinant lines from a cross between the cultivars Stellar (low-glucosinolate) and Major (high-glucosinolate) was used for singlemarker analysis and the interval mapping of QTLs associated with total seed glucosinolates. Two major loci, GSL-1 and GSL-2, with the largest influence on total seed aliphatic-glucosinolates, were mapped onto LG 20 and LG 1, respectively. Three loci with smaller effects, GSL-3, GSL-4 and GSL-5, were tentatively mapped to LG 18, LG 4 and LG 13, respectively. The QTLs acted in an additive manner and accounted for 71 % of the variation in total seed glucosinolates, with GSL-1 and GSL-2 accounting for 33% and 17%, respectively. The recombinant population had aliphatic-glucosinolate levels of between 6 and 160 µmoles per g(-1) dry wt of seed. Transgressive segregation for high seed glucosinolate content was apparent in 25 individuals. These phenotypes possessed Stellar alleles at GSL-3 and Major alleles at the four other GSL loci demonstrating that low-glucosinolate genotypes (i.e. Stellar) may possess alleles for high glucosinolates which are only expressed in particular genetic backgrounds. Gsl-elong and Gsl-alk, loci which regulate the ratio of individual aliphatic glucosinolates, were also mapped. Gsl-elong-1 and Gsl-elong-2, which control elongation of the α-amino-acid precursors, mapped to LG 18 and LG 20 and were coincident with GSL loci which regulate total seed aliphatic glucosinolates. A third tentative QTL, which regulates side-chain elongation, was tentatively mapped to LG 12. Gsl-alk, which regulates H3CS-removal and side-chain de-saturation, mapped to LG 20.

Abiotic elicitation of indole phytoalexins and resistance to Leptosphaeria maculans within Brassiceae.

Forty three accessions of Brassica species and one each of Sinapis and Raphanus were assessed for (i) resistance to Leptosphaeria maculans according to a coty-ledon-inoculation test and (ii) indole phytoalexin accumulation following abiotic elicitation with CuCl2. Five indole phytoalexins were determined in the lines following elicitation. Brassilexin, cyclobrassinin and cyclobrassinin sulphoxide were found within at least some lines of all species, whereas brassinin was only detected in B. oleracea and B. napus and methoxybrassinin within these two species and B. rapa and B. carinata. None of the five indole phytoalexins could be found in Raphanus sativus or Sinapis alba. The accumulation of large amounts of specific phytoalexins could be correlated with the presence of the different Brassica genomes. Lines possessing the B genome (B. nigra, B. juncea and B. carinata) which accumulated high amounts of brassilexin, displayed a hypersensitive resistance to infection whereas the majority of lines of B. oleracea, B. napus and B. rapa which did not accumulate large amounts of brassilexin, were susceptible. However, a B. nigra and a B. rapa line which only accumulated low amounts of brassilexin were highly resistant to the pathogen. Neither the accumulation of the other phytoalexins nor the total accumulation of indole phytoalexins could be related to resistance to L. maculans.