Synthesis and computational insights of flavone derivatives as potential estrogen receptor alpha (ER-α) antagonist.

Hormone-related breast cancer is mostly caused by interactions with estrogen receptor alpha (ER-α), which functions as a transcription factor to control the transcription of numerous genes. Flavones are considered a good substrate for the estrogen receptor. Substitution of the N-heterocyclic ring on the flavon structure may potentiate its anticancer effect. A series of flavon derivatives with an N-heteroaryl ring at the 4' position of the B ring of flavon were designed, prepared and evaluated for in vitro breast cancer activity. Binding interactions of the PzFL, PzF, PiFL, PiF and IFL compounds with ER-α were studied by molecular docking. Molecular dynamics simulation studies were carried out in order to determine the stability and convergence of protein-ligand complexes. The compounds were produced by cyclizing chalcones and chalcones were produced by Claisen-Schmidt condensation of substituted aldehydes and 2-hydroxy acetophenone. Breast cancer activity was evaluated by the MTT assay on MCF-7 cell lines. Also, compounds were studied for their estrogen receptor binding potential on the same cell lines. Molecular docking of compounds showed a good docking score. The molecular dynamics of these compounds expressed stable root mean square deviation, stable radius of gyration and low binding energy, suggesting that ligand bound to protein is quite stable in the complex. MTT assay on MCF-7 cell lines reported PzF and IFL were the most active compounds with lower IC50 values. ER-α binding assay of these compounds revealed the presence of binding interactions with receptors. This study offers a viable reference point for the design of flavon-incorporated N-heterocyclic ring derivatives as breast cancer compounds.Communicated by Ramaswamy H. Sarma.

Learning Curve of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy - an Analysis of Critical Perioperative and Surgical Outcomes among 155 Peritoneal Surface Malignancy Patients Treated at a Tertiary Care Cancer Centre.

AIMS: Various factors can influence the learning curve of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Initiating CRS and HIPEC programmes in low- and middle-income countries is challenging due to resource constraints and limited availability of expertise. We present our experience of CRS and HIPEC from a learning curve perspective among a cohort 155 peritoneal surface malignancy patients. MATERIALS AND METHODS: Patients undergoing CRS and HIPEC between May 2015 and February 2019 were included in the study. Patients were divided into two consecutive cohorts: the first 73 cases comprised the learning phase, group 1; the subsequent cohort of 82 patients were considered as the implementation phase, group 2. A comparative analysis of clinical and surgical outcome parameters was carried out between the two groups. RESULTS: The clinical spectrum was comparable among group 1/group 2. Most were ovarian (56.8%), colorectal (13.5%) and appendiceal (11.0%) malignancies. Group 2 had a higher number of moderate to high peritoneal cancer index patients (34.1% versus 19.1%), total peritonectomies (48.8% versus 45.2%), multi-visceral resections (colonic 41.5% versus 27.4%, small bowel 25.6% versus 19.1%, diaphragmatic 8.5% versus 6.5% and hepatic resections 8.5% versus 2.7%) and completeness of cytoreduction 0/1 rates (97.6% versus 93.1%). A lower incidence of intraoperative urological injuries (2.6% versus 12.3%) was noticed in group 2 (P = 0.007). Non-significant improvements seen in group 2 included surgery duration (6.0 ± 1.3 h versus 6.4 ± 1.7 h), intensive care unit stay (1.3 ± 1.1 days versus 1.8 ± 1.5 days), overall hospital stay (8.1 ± 0.9 days versus 8.8 ± 1.4 days) and reduction in Clavien-Dindo grade 3-4 complications (25.4% versus 36.9%). CONCLUSIONS: The results of the current study indicate that by implementing standard protocols and mentoring by an experienced team, a learning curve of CRS and HIPEC can be achieved in fewer than 75 cases. The baseline expertise of the treating team can also influence the learning curve.

Starch bio-based composite active edible film functionalized with Carum carvi L. essential oil: antimicrobial, rheological, physic-mechanical and optical attributes.

In the present study, the antimicrobial, rheological, mechanical, barrier and optical properties of Carrageenan and Manihot esculenta (composite) starch biobased edible film incorporated with caraway (Carum carvi L.) essential oil (EO) were investigated. The Minimum Inhibitory Concentration (MIC) of caraway oil against B. cereus, E. coli, P. aeruginosa and S. aureus were found to be 0.6, 1.4, 1.4 and 0.8% respectively. The Gas Chromatography- Mass Spectroscopy (GC-MS) of caraway EO expressed a distinct chromatogram peak for phenolic compounds. Rheological results of Film-Forming Solution (FFS) revealed solid-like viscoelastic behavior. Incorporation of caraway EO in the film caused significant (P < 0.05) increase in moisture, moisture absorption, bio-degradability in terms of film solubility, L value, total color difference (ΔE), haziness and transparency value, however, significantly (P < 0.05) decreased tensile strength and whiteness index were observed. The zone of inhibition of caraway EO incorporated films against all test bacteria were highly significant (P < 0.01) than control whereas antibacterial activity was found more towards gram-positive bacteria than gram-negative bacteria. No significant (P>0.05) changes in thickness, density, water activity, swelling, elongation at break, water vapor transmission rate, a and b value were observed with increasing caraway EO concentration. These results with some good rheological, physic-mechanical, antimicrobial and optical characteristics suggest the application of such active film into a variety of foods with improved food safety and quality. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05028-1.

Helping medical students to learn pathology more effectively.

CONTEXT: Teaching methods in pathology for undergraduate medical students are not effective. AIMS: To document measures that can be adopted by individual teachers that can excite the interest, participation of the students and help them learn pathology in a clinical reasoning context. SETTINGS AND DESIGN: Medical students in a large international medical school with class sizes of 700-900 were taught the pathology course in a period of sixteen weeks for two cohorts of students each year over a period of twenty years. SUBJECTS AND METHODS: Specific learning objectives were devised to achieve higher levels of cognitive domain including interpretation, analysis and problem solving of clinical data of patients related to the objectives. The teaching sessions were modified to provide for maximum active participation by students with effective feedback at multiple points. Additional learning tools like concept maps, clickers, modified essay questions, flipped classrooms, clinicopathological conferences, directed self-learning activities were included. Learning objectives and assessment tools for professional behavior and communication skills were included. RESULTS: The students actively participated in all the learning activities with enthusiasm and achieved the objectives as reflected in the performance in the in-house examinations and the USMLE step one examination which tests clinical vignette-based problem-solving principles of which around 70% are related to pathology. CONCLUSIONS: The teaching sessions in pathology were useful and effective with adaptation to interactive, clinical reasoning platforms for teaching and assessment.

Adrenal Myelolipoma Mimics Ectopic Adrenal or Renal Tissue: An Incidental Finding During Cadaveric Dissection.

CONTEXT: On naked eye examination adrenal myelolipoma (AML) tissue appears to be an ectopic adrenal or renal tissue, based on the similarity to their external texture. This necessitates a histo-pathological study for confirming the origin of the tissue. OBJECTIVE: To establish the origin and histological features of the incidental AML tissue found during cadaveric dissection and review the literature for similar findings with clinical picture and treatment description. SUBJECTS AND METHODS: Unilateral adrenal gland obtained from cadaveric dissection was subjected to histological study by H & E staining of the slides prepared. The literature review was done from articles published in PubMed indexed journals. CASE REPORT: A case of an incidental finding of AML during cadaveric dissection is presented which on naked eye examination was appearing to be an ectopic adrenal or renal tissue, based on the similarity to their external texture. On histological examination, a thin rim of adrenocortical tissue, surrounding the mature adipose tissue, and attenuated by islets of myeloid, erythroid and megakaryocytic cell lines in varying proportions, resembling the mature bone marrow morphology, was observed. The literature review on PubMed explains similar incidental post-mortem autopsy findings due to the asymptomatic nature of the tumor. The incidence of AML varied between 0.08% and 0.2% in the last decade of the 20th century, which increased up to 10 - 15% of incidental adrenal masses due to the widespread use of non-invasive imaging modalities leading to an increase in the diagnosis of the pathology. CONCLUSIONS: Before considering the ectopic incidence of tissue during cadaveric dissection, a histo-pathological examination is mandatory for confirmation. Adreno-myelolipoma is an asymptomatic post-mortem finding in 10-15% of cases of adrenal tissue which mimics ectopic adrenal gland or renal tissue due to its external texture.

Dose-dense Paclitaxel and Carboplatin as Neoadjuvant Chemotherapy for Stage IIB/IIIA Non-small Cell Lung Cancer - A Phase II trial.

AIMS: The approach to potentially resectable non-small cell lung cancer (NSCLC) remains controversial. There is a benefit of neoadjuvant chemotherapy (NACT), but the ideal regimen is unknown. We evaluated the efficacy and safety of dose-dense NACT in potentially resectable NSCLC in this phase II trial. MATERIALS AND METHODS: Paclitaxel at 80 mg/m2 on days 1, 8 and 15 with AUC-6 carboplatin on day 1, 3 weekly for four cycles was evaluated as NACT. Patients with Eastern Cooperative Oncology Group performance status 0-2, stage IIB and IIIA (with only non-bulky N2 nodes) were included. The primary end point was the objective response rate. Secondary end points included toxicity, progression-free survival, recurrence-free survival, complete resection rate and overall survival. The relative dose intensity (RDI) was calculated to define tolerability (CTRI/2016/05/006916). RESULTS: In total, 37 patients were enrolled (median age 55 years). Most (78.8%) were smokers. Most patients had adenocarcinoma (57.6%) and stage IIIA disease (81.0%) according to the seventh American Joint Committee on Cancer staging system. Seventy-eight per cent of patients completed four cycles. The objective response rate was 75.6% with a complete response in 10.8%. The mean RDI of paclitaxel was 88.61%, with 68.0% of patients able to maintain an RDI ≥85.0%. In total, 187 toxicity events were recorded (120 grade 1, 64 grade 2 and three grade 3 events). Common toxicities were peripheral neuropathy (20.3%), myalgia (19.8%), nausea (15.7%) and neutropenia (10.2%). There were no treatment-related deaths. Seventeen patients underwent surgery (lobectomy 82.4%). After a median follow-up of 47 months (95% confidence interval 27-50.7 months), the median progression-free survival was 9.6 months (7.4-17.4) and overall survival was 29.2 months (16.0-37.2). CONCLUSION: Dose-dense paclitaxel-carboplatin is feasible, safe and efficacious and should be evaluated further in potentially resectable NSCLC.

Effect of dopant concentration and the role of ZnS shell on optical properties of Sm3+ doped CdS quantum dots.

The role of samarium (Sm) dopant on the structural, morphological, and optical properties of CdS QDs and CdS/ZnS core/shell QDs was methodically reported. The synthesis of Sm-doped CdS QDs and CdS/ZnS QDs was carried out via a facile wet chemical method. The structure, chemical composition, and optical properties of the synthesized QDs were investigated by using X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy (RS), and photoluminescence (PL) spectroscopy. XRD analysis showed that the synthesized CdS QDs exhibited zinc blende structure which was not affected by doping Sm3+ ions. The particle size of the CdS:Sm and CdS:Sm (2%)/ZnS QDs was estimated to be ∼4 nm and ∼7 nm, respectively. Transmission electron microscopy (TEM) images revealed that the incorporation of Sm dopant did not significantly affect the size and morphology of CdS QDs, while the formation of the ZnS shell increased the particle size. XPS and XRD results confirmed the successful incorporation of Sm3+ ions into the CdS QDs. The effect of dopant concentration on the structural and luminescent properties was studied. The emission and excitation spectra of Sm3+-doped CdS QDs and CdS/ZnS QDs consisted of the characteristic lines corresponding to the intra-configurational f-f transitions. The energy transfer (ET) mechanism from the host to Sm3+ ions and the ET process through cross-relaxation between Sm3+ ions have been elucidated. The effect of the ZnS shell on the optical stability of the Sm3+-doped CdS QDs was studied in detail and the results showed that the CdS:Sm (2%)/ZnS QDs retained their good emission characteristics after 376 days of fabrication. The luminescent properties of Sm-doped QDs ranging from violet to red and PL lifetime extending to milliseconds demonstrated that these QDs are the potential materials for applications in white LEDs, biomarkers, and photocatalysis.

Impact of metabolic syndrome on re-stenosis development: role of drug-eluting stents.

Metabolic syndrome (MetS) is defined as a cluster of numerous cardiovascular risk factors, which encompasses obesity, dyslipidaemia, insulin resistance and hypertension. Patients with MetS are more prone to developing cardiovascular events than other patients. To date, several approaches such as physical exercise, dietary control and invasive and non-invasive therapeutic interventions for dyslipidaemia, hypertension and insulin resistance have been used to manage MetS. However, there is a progressive elevation in the incidence of fatal and non-fatal cardiovascular events due to the increased prevalence of obesity and diabetes. Percutaneous coronary intervention has emerged over the last few years as an effective revascularisation strategy for those with coronary artery disease, in parallel with the development of effective anti-platelet medications and newer drug-eluting stents. In recent years, considerable research efforts have been undertaken to elucidate the pathophysiology of re-stenosis and develop strategies to prevent re-stenosis following percutaneous transluminal coronary angioplasty and stent implantation. Although the rate of stent re-stenosis and target-lesion revascularisation has been reduced, there is little information in the literature on the outcome of MetS in the pathophysiology of re-stenosis. In this review article, we summarise the recent development and progress on re-stenosis and the role of drug-eluting stents, particularly in MetS.

Application of HR-MAS NMR spectroscopy for studying chemotype variations of Withania somnifera (L.) Dunal.

Withania somnifera (L.) Dunal (Solanaceae), commonly known as Ashwagandha, is one of the most valued Indian medicinal plants with a number of pharmaceutical and nutraceutical applications. Metabolic profiling has been performed by HR-MAS NMR spectroscopy on fresh leaf and root tissue specimens from four chemotypes of W. somnifera. The HR-MAS NMR spectroscopy of lyophilized defatted leaf tissue specimens clearly distinguishes resonances of medicinally important secondary metabolites (withaferin A and withanone) and its distinctive quantitative variability among the chemotypes. A total of 41 metabolites were identified from both the leaf and root tissues of the chemotypes. The presence of methanol in leaf and root tissues of W. somnifera was detected by HR-MAS NMR spectroscopy. Multivariate principal component analysis (PCA) on HR-MAS (1) H NMR spectra of leaves revealed clear variations in primary metabolites among the chemotypes. The results of the present study demonstrated an efficient method, which can be utilized for metabolite profiling of primary and secondary metabolites in medicinally important plants.

How can the postgraduate training program in pathology departments in India be improved?

There exists a wide variation in the competence of the postgraduate residents trained in pathology in different institutions across India. This results in strong disparities in the clinical diagnostic skills, teaching skills, research capabilities and the managerial skills of the graduates. The end users of this training, namely the community, clinicians and health care institutions would benefit from a more uniform and better trained pathologist. The article reviews the reasons for the variation in the quality of the training programs. The main deficiencies include, lack of well-defined criteria for recruitment of residents, training facilities, faculty resources, curriculum with well-defined learning objectives and competencies, hands-on experiences in diagnostic and research activities, diagnostic specimens and medical autopsies, exposure to molecular pathology, pathology informatics, electron microscopy, research experiences, communication skills, professional behavior and bioethics, business practices in pathology and quality assurance. There is also a lack of defined career tracks in various disciplines in laboratory medicine, standard protocols for evaluation and regional and national oversight of the programs. The steps for rectification should include defining the competencies and learning objectives, development of the curriculum including teaching methods, facilities and evaluation strategies, communication skills, professional behavior skills, teaching skills, legal aspects of practicing pathology and the various career pathways to subspecialties in pathology. The training should include defined exposure to molecular pathology, electron microscopy, quality control and assurance, laboratory accreditation, business aspects of pathology practice, review of literature, evidence-based medicine, medical autopsy and medical informatics. Efforts should be made to share human and laboratory resources between regional cooperation. The oversight and accreditation policies should be evolved and well-documented. Web-based platforms need to be developed for easy interaction among residents, faculty and administrators on a national level.

Telmisartan, a dual ARB/partial PPAR-γ agonist, protects myocardium from ischaemic reperfusion injury in experimental diabetes.

AIM: Apart from its angiotensin receptor blocker (ARB) activity, telmisartan is also a partial agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ). Therefore, we assessed whether telmisartan treatment attenuates myocardial ischaemia/reperfusion (I/R) injury in diabetic rats through PPAR-γ pathway. METHODS: Diabetic rats were randomized to receive vehicle (sham and I/R), telmisartan (10 mg/kg/day, orally), PPAR-γ antagonist GW9662 (1 mg/kg/day, intraperitoneally) or both for 14 days. On 15th day, excluding sham group, left anterior descending coronary artery occlusion was performed for 45 min followed by 1 h of reperfusion. Haemodynamic, biochemical, histopathological, ultrastructural, immunohistochemical (Bax and Bcl-2 protein), TUNEL positivity, infarct size and western blot studies were performed. RESULTS: Telmisartan treatment significantly improved cardiac function by normalizing mean arterial pressure, left ventricular pressure (±LVdP/dt(max) , a marker of myocardial contraction and relaxation), by decreasing left ventricular end-diastolic pressure (a marker of preload, 3.7 ± 0.41 vs. 7.3 ± 0.89, p < 0.001) and percent infarct area (37.52 ± 5.83 vs. 46.27 ± 3.20, p < 0.01) as compared to diabetic I/R group. Interestingly, GW9662 worsens the I/R injury (percent infarct area, 54.38 ± 6.48 vs. 46.27 ± 3.20, p < 0.01), whereas telmisartan with GW9662 (percent infarct area, 41.16 ± 8.23 vs. 46.27 ± 3.20, p < 0.05) showed lesser significant results as compared to telmisartan alone. Additionally, telmisartan significantly ameliorates activities of endogenous antioxidants, creatine kinase-MB isoenzyme, lactate dehydrogenase and prevented the increase of tumour necrosis factor-alpha and malondialdehyde in myocardium. Furthermore, telmisartan also decreased Bax expression (4.45 ± 1.24% vs. 10.25 ± 0.96%, p < 0.01), number of TUNEL-positive cells (6.2 ± 0.98% vs. 13.0 ± 1.6, p < 0.01), inflammation, myonecrosis and increased Bcl-2 expression (5.45 ± 0.15% vs. 1.24 ± 0.3%, p < 0.01). On the other hand, GW9662 treatment alone increased the Bax expression, TUNEL positivity and decreased Bcl-2 expression. Telmisartan protective effects were partially attenuated by a co-administration with GW9662. Western blot analysis showed that telmisartan treatment enhanced PPAR-γ expression, whereas GW9662 decreased it in myocardium. CONCLUSIONS: In addition to the class effect of ARBs, telmisartan has a beneficial effect in I/R injury in diabetic rats in part because of activation of PPAR-γ.

Histamine H4 receptor: a novel target for inflammation therapy.

Histamine, a low molecular weight amine has been extensively studied for its various pharmacological profiles. Until recently histamine was thought to act on three receptors - H1, H2 and H3. Merely a decade back, sequencing of human genome has revealed a new histamine receptor - H4 receptor. This 390 amino acid sequenced receptor has around 38% homology with histamine H3 receptor besides; the pharmacological profile of the protein is quite different from other histamine receptors. H4 receptor is mainly expressed in mast cells and leukocytes and involves various physiological functions related to inflammation and allergy. Potent selective H4 receptor agonists and antagonists have been synthesized and in vivo studies have indicated their action on H4 receptor. In this review, structure, expression, homology sequence of H4 receptor among the different species has been documented. Further, structure activity relationship (SAR) of H4 ligands on the basis of their nucleus has been discussed in depth. In addition, anti-inflammatory effects of H4 receptor antagonists, with special emphasis to JNJ7777120, a selective H4 receptor antagonist have been focused exhaustively.

Analysis of elevated temperature-induced inhibition of photosystem II using chlorophyll a fluorescence induction kinetics in wheat leaves (Triticum aestivum).

Wheat is the major crop plant in many parts of the world. Elevated temperature-induced changes in photosynthetic efficiency were studied in wheat (T. aestivum) leaves by measuring Chl a fluorescence induction kinetics. Detached leaves were subjected to elevated temperature stress of 35 °C, 40 °C or 45 °C. Parameters such as Fv/Fm, performance index (PI), and reaction centre to absorbance ratio (RC/ABS) were deduced using radial plots from fluorescence induction curves obtained with a plant efficiency analyser (PEA). To derive precise information on fluorescence induction kinetics, energy pipeline leaf models were plotted using biolyzer hp3 software. At 35 °C, there was no effect on photosynthetic efficiency, including the oxygen-evolving complex, and the donor side of PSII remained active. At 40 °C, activity was reduced by 14%, while at 45 °C, a K intermediate step was observed, indicating irreversible damage to the oxygen-evolving complex. This analysis can be used to rapidly screen for vitality and stress tolerance characteristics of wheat growing in the field under high temperature stress.

Endothelin receptor antagonist BQ-123 ameliorates myocardial ischemic-reperfusion injury in rats: a hemodynamic, biochemical, histopathological and electron microscopic evidence.

We investigated the effect of BQ-123, a selective endothelin-A (ET(A)) receptor antagonist in ischemia-reperfusion (IR) induced myocardial infarction (MI) with and without endothelin-1 (ET-1) challenge. MI was produced in rats by occlusion of left anterior descending coronary artery for 40 min and reperfusion for 120 min. ET-1 was administered immediately prior to coronary occlusion whereas vehicle or BQ-123 was administered 20 min after the occlusion. IR control group exhibited marked hemodynamic changes along with significant impairment of left ventricular functions. In addition, oxidative stress was increased, as evidenced by marked reduction in the activities of antioxidants and cardiac injury markers in myocardium. Furthermore, light microscopic and ultrastructural changes revealed myocardial necrosis, edema and inflammation. Prior administration of ET-1 acts synergistically with IR injury and further aggravates the impairment of ventricular functions, increased percent infarct area and decreased antioxidant levels. However, treatment with BQ-123 (1 mg/kg, IV) with or without ET-1 caused significant improvement in cardiac functions, percent infarct area, decreased malonaldehyde level, restored myocardial enzymes activities and maintained the redox status of the myocardium as compared to IR control group. Further, histopathological and ultrastructural studies reconfirmed the protective action of BQ-123. The results of present study suggest that ET-1 acting via ET(A) receptor may exaggerate myocardial damage produced by IR injury and selective blockade of ET(A) receptor by BQ-123 might offer potential cardioprotective action.

Synthesis, anti-bacterial and anti-fungal activities of some novel Schiff bases containing 2,4-disubstituted thiazole ring.

A series of arylidene-2-(4-(4-methoxy/bromophenyl) thiazol-2-yl) hydrazines (4a-z) and 1-(4-(4-methoxy/bromophenyl) thiazol-2-yl)-2-cyclohexylidene/cyclopentylidene hydrazines (5a-b/6a-b) were synthesized, characterized and screened for their antimicrobial activities. The structures of synthesized compounds were established by spectroscopic (FT-IR, (1)H NMR, (13)C NMR, Mass) and elemental analyses. Both the anti-bacterial and anti-fungal activities with MIC values of compounds were evaluated. The results of anti-bacterial screening reveal that among all the compounds screened eight compounds showed moderate to good anti-bacterial activity while ten of the newly synthesized compounds displayed good to excellent anti-fungal activity. Among the tested compounds, the most effective compounds with MIC value in the range of 6.25-25 microg/ml are 4a, 4n, 4z, 5a, 5b, 6a and 6b against three fungal strains viz. Candida albicans, Cryptococcus neoformans and Aspergillus flavus.

Protective effect of Calotropis procera latex extracts on experimentally induced gastric ulcers in rat.

AIM OF THE STUDY: Calotropis procera is a wild growing plant with multifarious medicinal properties. The present study was carried out to evaluate the effect of dried latex (DL) of Calotropis procera and its methanol extract (MeDL) against gastric ulcers induced in rats. MATERIALS AND METHODS: Aqueous suspension of DL (20 and 100mg/kg) and MeDL (10 and 50mg/kg) were given orally to 36h fasted rats and ulcers were induced by ethanol, pyloric ligation and aspirin. Parameters like ulcer score and levels of oxidative stress markers were measured in all the models. The effect on gastric hemorrhage and tissue histology was studied in ethanol model and on acidity, pH and volume of gastric secretion was evaluated in pyloric ligation model. The protective effect of DL and MeDL was compared with that of standard anti-ulcer drug famotidine (20 mg/kg). RESULTS: DL and MeDL produced 85-95% inhibition of gastric mucosal damage in ethanol model and 70-80% inhibition in aspirin model. The protective effect of these extracts was associated with marked reduction in gastric hemorrhage, maintenance of tissue integrity and normalization of levels of oxidative stress markers like glutathione, thiobarbituric acid reactive substances and superoxide dismutase. Like famotidine, DL and MeDL decreased the gastric acidity from 376.17+/-21.47 mequiv./l to 163.88+/-6.86 and 201.48+/-8.86 mequiv./l respectively in pyloric ligation model. These extracts increased the gastric pH without affording any protection to gastric mucosa in this model. CONCLUSION: The latex of Calotropis procera has the therapeutic potential to relieve gastric hyperacidity and to prevent gastric ulceration induced by necrotizing agents.