Synthesis, crystal structures, spectroscopy, and quantum chemical studies on the 4-dimethylaminopyridinium-2,4-dinitrophenolate: an organic NLO material for optoelectronics.

CONTEXT: In this work, the 4-dimethylaminopyridinium-2,4-dinitrophenolate (4DMAP + 2,4DNP) by slow evaporation solution growth method has been presented. The Fourier transform infrared (FT-IR) (4000-400 cm-1) and FT-Raman (4000-50 cm-1) spectra were recorded for the grown crystal. METHODS: The computational calculation has been carried out with density functional theory (DFT) in ground state with Gaussian program package. Optimized geometrical parameters (bond distances, bond angles, and dihedral angles) have been obtained and compared with X-ray crystallography data. The calculated fundamental vibrational frequencies from DFT/B3LYP with 6-311 + + G(d,p) level of theory were scaled so as to agree with the observed results, and the scaling factors were reported. RESULTS: Experimental and computed ultraviolet-visible (UV-Vis) spectra in acetone and methanol solvents were found comparable to each other. Furthermore, the frontier molecular orbitals (FMOs) energies, molecular electrostatic potential (MEP), nonlinear optical (NLO), hirshfeld surface (HS), and global chemical descriptors of the molecule were also calculated. The thermal stability and the melting point of the title compound were analyzed by the thermogravimetric analysis/differential thermal analysis (TGA/DTA) techniques. The mechanical behavior of the organic single crystal was measured by Vickers micro-hardness method. The third-order nonlinear optical properties such as nonlinear refractive index (n2), nonlinear absorption coefficient (ß), optical nonlinear susceptibility Reχ(3), and optical nonlinear susceptibility Imχ(3) were calculated by using the open and closed aperture Z-scan technique. CONCLUSION: The theoretical and experimental NLO values clearly proposed that the nonlinearity of 4DMAP + 2,4DNP molecule could be helped as a potential candidate for optical limiting, frequency doubling, and optical switching applications.

Biocompatible Films of Collagen-Procyanidin for Wound Healing Applications.

The study investigated the effect of polyphenols present in Cassia auriculata (CA) leaves in enhancing the stability of the collagen protein and the wound healing potential of collagen films. The crude ethanol extract of CA was analyzed for the presence of phytochemicals and purified by column chromatography using solvents with increasing polarity. The ethanol eluted active fractions (EEAF) that precipitated gelatin was characterized using HP-TLC, FTIR spectroscopy, ESI-FT-MS/MS, and 1H NMR spectroscopy. The active compound was identified to be procyanidin B belonging to the proanthocyanidins group. The wound healing property of EEAF and collagen type I extracted from Clarias batrachus fish skin and the bovine tendon was assessed by in vitro scratch assay on L929 mice fibroblast cell lines. The EEAF-treated collagen coating enhanced in vitro wound closure in comparison with the uncoated dish. It was observed that EEAF treatment improved the physical strength of collagen films. The in vivo wound healing of the EEAF-treated collagen film was examined in male Wister rats and the wound site tissues were assessed. In vivo wound examination showed enhanced healing with EEAF incorporated collagen films. Comparatively, the EEAF-treated bovine tendon collagen films showed improved physical properties and better wound healing property than fish collagen films.

Nutritional Adequacy in Mechanically Ventilated Patient: Are We Doing Enough?

BACKGROUND: Critically ill patients are under stress, leading to a catabolic response and higher energy expenditure. The associated malnutrition leads to adverse outcomes. AIMS AND OBJECTIVES: This study aims to assess the nutritional adequacy (>80% of prescribed calories) in mechanically ventilated (MV) patients and its effects on patients' outcomes. It also aims to identify the causes of deviation from the nutrition prescription. MATERIALS AND METHODS: This is a prospective observational study involving all adult critically ill patients requiring MV for >48 hours. Patients were prescribed enteral nutrition (EN) targeted to achieve 25 kcal/kg (IBW) of energy and 1.2 g/kg of proteins daily. Standard polymeric formula feeds were initiated as continuous infusion as per the feeding protocol in the intensive care unit (ICU). Data were collected on demography, body mass index (BMI), indication for ICU admission, admission category, and admission APACHE II and SOFA scores, and nutritional risk was captured with mNUTRIC score. Nutritional data on type of feed initiated, amount of calories prescribed/achieved, time taken to initiate feeds, reasons for not starting/delay in the initiation of feeds, time taken to achieve the prescribed calories, and reasons for interruptions of feeds were collected. Primary outcome analyzed was adequacy of nutrition (>80% prescribed dose), and secondary outcomes analyzed were ventilator days and ICU LOS. RESULTS: A total of 622 MV patients were analyzed. 36.1% of patients were at nutritional risk (mNUTRIC χ5). 89% of patients received EN, and the time taken to start EN in these patients was 10 hours (6-20) (median [IQR]). Only 29.6% of patients achieved nutritional adequacy. Time taken for this was 36 hours (median). On average, patients on MV received 63% (1025 kcal) and 57% (41 g) of their prescribed calories and proteins, respectively. The most common reasons for withholding feeds were airway-related procedures (68.2%) followed by GI intolerance (15%). Frequent interruptions of EN, patients on >1 vasopressors, and surgical admissions were reasons for nutritional inadequacy. Nutritional adequacy had no impact on clinical outcomes. CONCLUSION: Despite following guidelines and feeding protocols, there exists a wide gap between prescribed nutrition and what is actually delivered in MV patients. HOW TO CITE THIS ARTICLE: Kalaiselvan MS, Arunkumar AS, Renuka MK, Sivakumar RL. Nutritional Adequacy in Mechanically Ventilated Patient: Are We Doing Enough? Indian J Crit Care Med 2021;25(2):166-171.

Comparison of acute physiology and chronic health evaluation II (APACHE II) and acute physiology and chronic health evaluation IV (APACHE IV) severity of illness scoring systems, in a multidisciplinary ICU.

BACKGROUND AND AIMS: Outcome prediction of critically ill patients is an integral part of care in an Intensive Care Unit (ICU). Acute Physiology and Chronic Health Evaluation (APACHE) scoring systems provide an objective means of mortality prediction in ICU. The aim of this study was to compare the performance of APACHE II and IV scoring system in our ICU. MATERIAL AND METHODS: All patients admitted to the ICU between January and June 2014 and who met the inclusion criteria were evaluated. APACHE II and IV score were calculated during the first 24 h of ICU stay based on the worst values. All patients were followed up till discharge from the hospital or death. Statistical analysis was performed using SPSS version 19.0. Discrimination of the model for mortality was assessed using receiver operating characteristic curve and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: Of a total 1268, 1003 patients were included in this study. The mean (±standard deviation) admission APACHE II score was 19.4 ± 8.9, and APACHE IV score was 59.1 ± 27.2. The APACHE scores were significantly higher among nonsurvivors than survivors (P < 0.001). The overall crude hospital mortality rate was 17.6%. APACHE IV had better discriminative power area under the ROC curve ([AUC] -0.82) than APACHE II (AUC-0.75). Both APACHE II and APACHE IV had poor calibration. CONCLUSIONS: APACHE IV showed better discrimination compared to APACHE II in our ICU population. Both APACHE II and APACHE IV had poor calibration. However, APACHE II calibrated better compared to APACHE IV.

An analysis of the predictors of mortality and morbidity in patients admitted after suicidal hanging to an Indian multidisciplinary Intensive Care Unit.

BACKGROUND AND AIMS: Hanging is a frequently used method to attempt suicide in India. There is a lack of data in the Indian population regarding clinical features and outcomes of suicidal hanging. The purpose of this study was to evaluate the factors affecting mortality and morbidity in patients admitted with suicidal hanging to the Intensive Care Unit (ICU). METHODS: A 6-year retrospective study of adult patients admitted to the ICU with suicidal hanging was analysed for demographics, mode of hanging, lead time to emergency room (ER) admission, clinical presentation, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, admission Glasgow coma scale (GCS) and neurological outcomes. The primary outcome was in-hospital mortality rate. Secondary outcomes were hospital length of stay (LOS), ICU-LOS, time for neurological recovery, organ support and duration of mechanical ventilation. Statistical analysis was performed using the Student's t-test for continuous variables and Chi-square test for categorical variables. RESULTS: We analysed data of 106 patients. The median age was 27 years [Interquartile Range (IQR) (22-34)]. The median lead time to ER admission was 1 h [IQR (0.5-1.4)] with median ICU stay of 3 days [IQR (2-4)]. Vasopressors were administered to 27.4% patients. GCS was ≤7 in 65% patients, and 84.9% patients received mechanical ventilation. Mortality rate was 10.3%. Survivors recovered with normal organ function. CONCLUSION: Suicidal hanging is associated with significant mortality. Admission GCS, APACHE II and 48 h SOFA score were predictors of poor outcome.

Clinical Features and Outcomes of Patients with Posterior Reversible Encephalopathy Syndrome.

AIMS: The aim of this study was to study the clinical features and outcomes of patients with posterior reversible encephalopathy syndrome (PRES) admitted to the Intensive Care Unit (ICU). SUBJECTS AND METHODS: All adult patients admitted to our ICU with acute onset neurologic symptoms with focal vasogenic edema on magnetic resonance imaging (MRI) were included in the study. Data were collected on demography, coexisting illness, admission severity of illness, neurological symptoms, blood pressure, treatment initiated, and MRI findings. Outcome data collected included mortality, ICU average length of stay (ALOS), number of ventilator days, and neurological disability at discharge assessed by modified Rankin scale (MRS). RESULTS: Fourteen patients were admitted with PRES. Thirteen patients were female, and their mean age was 31.5 ± 8.3 years. Etiology of PRES included eclampsia (64.2%), lupus nephritis (21.4%), CKD (7.1%), and hypertension (n = 1 [7.1%]). The most common presenting symptom was seizure (92.8%), followed by visual disturbance (42.8%), headache (42.8%), encephalopathy (14.2%), and status epilepticus (14.2%). The Glasgow coma scale on admission was 12.3 ± 2.9. High blood pressure was seen in 12 patients 85.7%; their mean systolic and diastolic pressures were 173 ± 10.2 and 110 ± 8.6 mmHg, respectively. MRI showed that parieto-occipital region was most commonly involved (92.8%), followed by frontal lobe (42.8%). ICU ALOS was 4.35 ± 2.4 days and mean ventilator days was 1.7 ± 2.0 days. One patient (1/14 [7.4%]) died of multiorgan failure and 13 patients were discharged with no residual neurological deficit (MRS, 0). CONCLUSIONS: PRES is a potentially reversible disorder with prompt recognition and control of blood pressure.

Use of Nutrition Risk in Critically ill (NUTRIC) Score to Assess Nutritional Risk in Mechanically Ventilated Patients: A Prospective Observational Study.

CONTEXT: Nutritional risk assessment must be done on all critically ill patients. Malnutrition in intensive care unit (ICU) patients is associated with adverse clinical outcomes. Traditional scoring systems cannot be used for screening in mechanically ventilated (MV) patients because these patients are unable to provide information on their history of food intake and weight loss. The Nutrition Risk in Critically ill (NUTRIC) score is the appropriate nutritional assessment tool in MV patients. AIMS: This prospective observational study was conducted to identify the nutritional risk in MV patients using modified NUTRIC (mNUTRIC) score (with the exception of interleukin-6). PATIENTS AND METHODS: All adult patients admitted to the ICU and required MV for more than 48 h were included in the study. Data were collected on variables required to calculate mNUTRIC score. Patients with mNUTRIC score ≥5 are considered at nutritional risk. Outcome data were collected on ICU length of stay, ventilator-free days, and mortality. RESULTS: A total of 678 MV patients fit into the inclusion criteria. Majority of the patients were male (67%). Mean age of the patients was 55 years. About 288 (42.5%) patients were at high nutritional risk (mNUTRIC score ≥5). Patients with high mNUTRIC score ≥5 had longer mean ICU average length of stay of 9.0 (±4.2) versus 7.8 (±5.8) mean (± standard deviation) days (P < 0.01) and higher mortality 41.4% versus 26.1% (P < 0.0) compared to patients with low NUTRIC score (≤4). High mNUTRIC score (≥5) predicted mortality with area under the curve of 0.582 (95% confidence interval 0.535-0.628). CONCLUSIONS: Nearly 42.5% of MV patients admitted to ICU were at nutritional risk, and high mNUTRIC score was associated with increased ICU length of stay and higher mortality.

Outcome of Noncardiac Surgical Patients Admitted to a Multidisciplinary Intensive Care Unit.

CONTEXT: Surgical procedures carry significant morbidity and mortality depending on the type of surgery and patients. There is a dearth of evidence from India on the outcome of surgical patients admitted to an Intensive Care Unit (ICU). AIMS: We aimed to describe the incidence and risk factors of postoperative complications and mortality in noncardiac surgical patients admitted to the ICU. SETTINGS AND DESIGN: This was a prospective observational study on all perioperative patients admitted to a multidisciplinary ICU for 18 months. SUBJECTS AND METHODS: Data on demography, admission Acute Physiology and Chronic Health Evaluation II (APACHE-II), Sequential Organ Failure Assessment (SOFA) scores, perioperative course, type and duration of surgery, reason for ICU admission, ICU interventions, and perioperative complications were recorded. The primary outcomes analyzed were perioperative complications and mortality. RESULTS: The study included 762 patients with a mean age of (mean ± standard deviation [SD]) 50.5 ± 18 years and a male (58.4%) preponderance. The mean (±SD) admission APACHE-II and SOFA scores were 15 (±5.0) and 4.26 (±2.6), respectively. The most common reason for ICU admission was elective mechanical ventilation 50%, followed by prolonged surgery 26.2% and hemodynamic instability 21.2%. Most (51.1%) patients belonged to American Society of Anaesthesiologists physical Status III or IV and Lee's surgical risk Category I and II (66.8%). The most common surgical procedures performed were gastro-intestinal (28.5%) followed by interventional Neuro-radiology (14.0%) and orthopedic (13.9%). Overall perioperative complications were observed in 51.4% (n = 392). Common complications observed were hemodynamic instability 24%, hypothermia 17.2%, sepsis 17.3%, poor glycemic control 11.2%, perioperative myocardial infarction 7.1%, cardiac arrest 0.13%, and acute kidney injury (AKI) 10.1%. The overall hospital mortality was 7.9%. Multivariate logistic regression analysis showed that admission APACHE-II score, sepsis, AKI, and ICU length of stay were independent predictors for mortality. CONCLUSIONS: High risk perioperative patients after noncardiac surgery have significant mortality and morbidity.

Clinical profile and outcome of patients with severe sepsis treated in an intensive care unit in India

Introduction: Sepsis is the leading cause of intensive care unit (ICU) admissions and is associated with high mortality. Objectives: To identify the incidence, risk factors and outcome of patients with severe sepsis and septic shock. Methods: A prospective observational study was done in a multidisciplinary ICU over a period of 18 months. We included all adult patients admitted to ICU with features of severe sepsis and septic shock as per SCCM/ACCP guidelines. Data related to demography, co-existing illnesses, parameters to assess Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, other relevant laboratory data, source of infection, organ failures and supportive measures given were recorded. Primary outcome data on mortality was collected and secondary outcome data on ventilator days, ICU length of stay (ALOS) and ventilator free days were recorded. Results: A total of 1162 patients were screened and 356 patients had severe sepsis. Incidence of severe sepsis was 30.6% and mortality rate was 51.6%. APACHEII (23.37 ± 9.47) and SOFA (7.58 ± 4.05) scores at admission were high. Most common source of infection was from the respiratory tract (37.2%) followed by urinary tract (10.3%) and intra-abdominal (9.5%) infections. About 63% of patients required ventilator support, 25.5% of patients required vasopressor support despite adequate fluid resuscitation and one third of patients required renal replacement therapy (35.7%). Haematocrit, total leucocyte count, serum bilirubin and SOFA scores were significantly higher among non-survivors. Conclusions: Incidence of severe sepsis was high and was associated with a poor patient outcome in an ICU in India.

A retrospective study of clinical profile and outcomes of critically ill patients with heat-related illness.

BACKGROUND AND AIMS: Heat-related illness (HRI) due to high ambient temperatures is a common feature during the Indian summer. HRI often results in Intensive Care Unit (ICU) admissions and are associated with significant morbidity and mortality. However, published report on the effects of HRI among the Indian population is lacking. This study was undertaken to identify the profile of patients admitted to ICU with clinical features of HRI and study their clinical outcomes. METHODS: This was a retrospective case series of patients admitted with features of HRI during the summer of 2012 in our multidisciplinary ICU. Data on demographics, co-morbid illness, admission severity of illness (Acute Physiology and Chronic Health Evaluation II [APACHE II]), organ failure scores (Sequential Organ Failure Assessment [SOFA]) and neuroimaging studies were collected. Outcome data studied included mortality, ICU length of stay (LOS), ventilator days and hospital LOS. Statistical analysis was performed using Student's t-test, Chi-square test and multivariate analysis. RESULTS: Twenty-six patients met the diagnostic criteria for HRI. Fifteen were males. The mean age was 53.12 ± 18.6 years. Mean APACHE II score was 19.6 ± 7.7 and mean SOFA score was 7.5 ± 2.6. The common presenting symptoms were fever with neurological impairment (100%) and gastrointestinal symptoms (30%). Major organ systems involvement include neurological (100%), renal (57%), hepatic (34%) and coagulation abnormalities (26%). Most common metabolic abnormality noted was hyponatraemia (73%). Magnetic resonance imaging findings suggestive of heat stroke were seen in 5 of 26 patients. Mortality rate was 34%. 8 of 17 survivors had residual neurological impairment. CONCLUSION: HRI carries a high mortality and significant neurological morbidity.

Robust stochastic stability of discrete-time fuzzy Markovian jump neural networks.

This paper focuses the issue of robust stochastic stability for a class of uncertain fuzzy Markovian jumping discrete-time neural networks (FMJDNNs) with various activation functions and mixed time delay. By employing the Lyapunov technique and linear matrix inequality (LMI) approach, a new set of delay-dependent sufficient conditions are established for the robust stochastic stability of uncertain FMJDNNs. More precisely, the parameter uncertainties are assumed to be time varying, unknown and norm bounded. The obtained stability conditions are established in terms of LMIs, which can be easily checked by using the efficient MATLAB-LMI toolbox. Finally, numerical examples with simulation result are provided to illustrate the effectiveness and less conservativeness of the obtained results.

Pharmacognostic, Phytochemical and Anti-microbial studies of Solanum indicum leaves.

The leaves of Solanum indicum showed the presence of stellate trichome. Ethanolic extract of leaves Solanum indicum showed antibacterial activity against Staphylococcus aureus, Bacillus cereus, Escherichia coli where as chloroform extract, acetone extract and ethanol showed anti bacterial against pseudomonas. The aqueous extract did not show any anti microbial activity towards the tested organism. None of the extract showed anti fungal activity.

Detection of Amp C beta lactamases production in Escherichia coli & Klebsiella by an inhibitor based method.

BACKGROUND & OBJECTIVE: Detection of AmpC-mediated resistance in Gram-negative organisms poses a problem due to misleading results in phenotypic tests. There are no recommended guidelines for detection of this resistance mechanism and there is a need to address this issue as much as the detection of extended spectrum beta lactamases (ESBLs) since both may co-exist and mask each other. Though resistance to cefoxitin is used as a screening test, it does not reliably indicate Amp C production. This study was undertaken to detect Amp C beta lactamases in certain Gram-negative bacteria employing an inhibitor base test using boronic acid. METHODS: A total number of 76 consecutive non repetitive clinical isolates of Escherichia coli (n=67) and 9 Klebsiella pneumoniae (n=9) obtained over a period of two months, were screened for amp C production by disc diffusion method using cefoxitin (30 microg) dics and confirmed by inhibitor based test using boronic acid as inhibitor. RESULTS: A total of 36 of 76 isolates (47.3%) screened harboured amp C enzymes, of which a majority 31 (86.1%) co-produced ESBL enzymes. Pure ampC production was seen in 7 (9.2%) of isolates only. INTERPRETATION & CONCLUSION: Most of the amp C producers also produced ESBL enzymes. The inhibitor based test was useful in identifying cefoxitin susceptible amp C producers and could also effectively differenciate ESBL from amp C producing isolates.

Ameliorative effect of vitamins (alpha-tocopherol and ascorbic acid) on PCB (Aroclor 1254) induced oxidative stress in rat epididymal sperm.

The aim of this study was to investigate the possible protective role of vitamins on PCB (Aroclor 1254)-induced spermiotoxicity using qualitative, quantitative and biochemical approaches. Adult male albino rats of Wistar strain were randomly divided into four groups, each group consists of six animals. The control group received corn oil, the second group of rats were administered Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. The third group of rats were treated with Aroclor 1254 along with alpha-tocopherol (50 mg/kg of bw/day) for 30 days, while the fourth group of rats were treated with Aroclor 1254 along with ascorbic acid (100 mg/kg bw/day) orally for 30 days. Twenty-four hours after the last treatment, control and experimental animals were killed by decapitation. Sperm was collected from the cauda epididymal region and its count and motility were detected. Sperm was sonicated and used for the estimation of reactive oxygen species (ROS) [hydroxyl radical (HO(*)) and hydrogen peroxide (H(2)O(2))], non-enzymic antioxidants [alpha-tocopherol, ascorbic acid and reduced glutathione (GSH)], activity of enzymic antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) glutathione reductase (GR) and glutathione-S-transferase (GST)] and lipid peroxidation (LPO). The result of this experiment shows that PCB significantly decreases the level of alpha-tocopherol, ascorbic acid and GSH and the activities of SOD, CAT, GPx, GR and GST with elevated levels of ROS and LPO. In addition, decreased epididymal sperm motility and count were observed. Simultaneous supplementation with alpha-tocopherol and ascorbic acid restored these parameters to that of normal range. In conclusion, alpha-tocopherol and ascorbic acid exhibited protective effect on sperm by inhibiting PCB-induced ROS generation.

Quercetin induces p53-independent apoptosis in human prostate cancer cells by modulating Bcl-2-related proteins: a possible mediation by IGFBP-3.

Quercetin, a flavonoid found in onion, grapes, green vegetables, etc., has been shown to possess potent antiproliferative effects against various malignant cells. We report insulin-like growth factor-binding protein-3 (IGFBP-3) as an effector of quercetin-induced apoptosis in human prostate cancer cell lines in a p53-independent manner. We evaluated the production of IGFBP-3 in quercetin-treated cells. Apoptosis was studied in quercetin-treated cells to study the IGFBP-3-mediated role with flow cytometry and DNA fragmentation. Protein expressions of Bcl-2, Bcl-x(L), and Bax were studied by Western blot. Increased production of IGFBP-3 was associated with the increased ratio of proapoptotic to antiapoptotic members of the Bcl-2 family. In quercetin-treated PC-3 cells, an increase in Bax protein expression and a decrease in Bcl-x(L) protein and Bcl-2 protein were observed. As PC-3 is a p53-negative cell line, these modulations of proapoptotic proteins and induction of apoptosis were independent of p53. The level of IGFBP-3 on the response of PC-3 cells to quercetin was examined. There was a twofold increase in IGFBP-3 level in conditioned media of 100 microM quercetin-treated cells. Quercetin also brought a peak at sub-G1 in PC-3 cells. Thus, increased level of IGFBP-3 was associated with increased proapoptotic proteins and apoptosis in response to quercetin, suggesting it may be a p53-independent effector of apoptosis in prostate cancer cells via its modulation of the Bax/Bcl-2 protein ratio.

Effects of quercetin on insulin-like growth factors (IGFs) and their binding protein-3 (IGFBP-3) secretion and induction of apoptosis in human prostate cancer cells.

BACKGROUND: Quercetin, the predominant flavonoid, has been reported to lower the risk of several cancers. This flavonoid found in onion, grapes, green vegetables, etc. has been shown to possess potent antiproliferative effects against various malignant cells. This study was designed to investigate its effects on insulin-like growth factors (IGFs) and their binding protein-3 (IGFBP-3) proteins secretion and also apoptosis induction in the human prostate cancer cell line, PC-3. METHODS: We evaluated the secretion of IGF-I, -II and IGFBP-3 in quercetin treated cells by immunoradiometric (IRMA) method. Apoptosis was studied in quercetin treated cells by TUNEL and DNA fragmentation. Protein expressions of Bcl-2, Bcl-xL, Bax and caspase-3 were studied by western blot. RESULTS: At a dose of 100 microM concentration, we observed increased IGFBP-3 accumulation in PC-3 cells conditioned medium with a dose dependent increase with 2 fold over a base line, and significantly reduced the both IGF-I and IGF-II levels. Apoptosis induction was also confirmed by TUNEL assay. Bcl-2 and Bcl-xL protein expressions were significantly decreased and Bax and caspase-3 were increased. CONCLUSION: These results suggest that the decreased level of IGFs could be due to the increased levels of IGFBP-3, because of the high binding affinity towards IGFs, thereby decreasing the cell proliferation. The increased level of IGFBP-3 was associated with increased pro-apoptotic proteins and apoptosis in response to quercetin, suggesting it may be a p53-independent effector of apoptosis in prostate cancer cells.

Quercetin downregulates matrix metalloproteinases 2 and 9 proteins expression in prostate cancer cells (PC-3).

BACKGROUND: Cancer metastasis, involving multiple processes and various cytophysiological changes, is a primary cause of cancer death and may complicate the clinical management, even lead to death. Quercetin is a flavonoid and widely used as an antioxidant and recent studies have revealed its pleiotropic anticancer and antiproliferative capabilities. Gelatinases A and B (matrixmetalloproteinases 2 and 9) are enzymes known to involve in tumor invasion and metastases. In this study, we observed the precise involvement of quercetin role on these proteinases expression and activity. DESIGN AND METHODS: PC-3 cells were treated with quercetin at various concentrations (50 and 100 microM), for 24 h period and then subjected to western blot analysis to investigate the impact of quercetin on matrix metalloproteinase-2 (MMP-2) and 9 (MMP-9) expressions. Conditioned medium and cell lysate of quercetin-treated PC-3 cells were subjected to western blot analysis for proteins expression of MMP-2 and MMP-9. Gelatin zymography was also performed in quercetin treated PC-3 cells. RESULTS: The results showed that quercetin treatment decreased the expressions of MMP-2 and MMP-9 in dose-dependent manner. The level of pro-MMP-9 was found to be high in the 100 microM quercetin-treated cell lysate of PC-3 cells, suggesting inhibitory role of quercetin on pro-MMP-9 activation. Gelatin zymography study also showed the decreased activities of MMP-2 and MMP-9 in quercetin treated cells. CONCLUSION: Hence, we speculated that inhibition of metastasis-specific MMPs in cancer cells may be one of the targets for anticancer function of quercetin, and thus provides the molecular basis for the development of quercetin as a novel chemopreventive agent for metastatic prostate cancer.

Anticancer effects of ethanolic neem leaf extract on prostate cancer cell line (PC-3).

Prostate cancer (PC) is the most prevalent cancer and the leading cause of male cancer death. Azadirachta indica (neem tree) has been used successfully centuries to reduce tumors by herbalists throughout Southeast Asia. Here the present study indicated that an ethanolic extract of neem has been shown to cause cell death of prostate cancer cells (PC-3) by inducing apoptosis as evidenced by a dose-dependent increase in DNA fragmentation and a decrease in cell viability. Western blot studies indicated that treatment with neem extract showed decreased level of Bcl-2, which is anti-apoptotic protein and increased the level of Bax protein. So the neem extract could be potentially effective against prostate cancer treatment.

Antiproliferative effect of diallyl disulfide (DADS) on prostate cancer cell line LNCaP.

Garlic has been used throughout the world to treat coughs, toothache, earache, dandruff, hypertension, hysteria, diarrhoea, dysentery, diptheria, vaginitis and many other conditions. Garlic contains a complex mixture of oil and water-soluble organosulfur compounds. Diallyl disulfide (DADS), an oil-soluble constituent of garlic seems to be effective in reducing tumour cells originating from colon, lung and skin. Hence our present study focuses on the dose-dependent effect of DADS on an androgen-dependent prostate cancer cell line. Various concentrations of DADS ranging from 25 to 100 microM were given to LNCaP cells and the activity of lactate dehydrogenase (LDH) prostatic acid phosphatase (PAcP) and the level of prostate specific antigen were studied. DADS reduced the secretory activity of LNCaP cells with the gradual increase in dosage. DADS was found to act as a good antiproliferative agent, which was confirmed by proliferation assay. DADS also induced apoptosis and nuclear segmentation in the higher doses.

Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression.

Prostate cancer is the major health problem and the leading cause of male cancer death. Quercetin is a novel antitumor and antioxidant, whose molecular mechanism involved in cell cycle arrest in androgen independent prostate cancer cells remains unclear. In this study, we investigated the effects of quercetin on proliferation and cell cycle arrest by modulation of Cdc2/Cdk-1 protein in prostate cancer cells (PC-3). PC- 3 cells are human androgen independent cancer cells and were cultured with quercetin at concentrations of 50 and 100 microM for 24 h. Cell proliferation, apoptosis and cell cycle distribution were analyzed. Expression of Cdc2/Cdk-1, cyclin B1, cyclin A, p21/Cip1, pRb, pRb2/p130, Bcl-2, Bcl-X(L), Bax and caspase-3 proteins were studied with western blot analysis. Addition of quercetin led to substantial decrease in the expression of Cdc2/Cdk-1, cyclin B1 and phosphorylated pRb and increase in p21. Flowcytometric analysis showed that quercetin blocks G2-M transition, with significant induction of apoptosis. Apoptosis markers like Bcl-2 and Bcl-X(L) were significantly decreased and Bax and caspase-3 were increased. From this study, it was concluded that quercetin inhibits prostate cancer cell proliferation by altering the expression of cell cycle regulators and apoptotic proteins.