Noni enhances the anticancer activity of cyclophosphamide and suppresses myelotoxicity and hepatotoxicity in tumor-bearing mice.

BACKGROUND AND AIM: Morinda citrifolia fruit juice (noni) is an herbal remedy documented to have antioxidant properties. It has been suggested that prevention of carcinogen-DNA adduct formation and the antioxidant activity of NJ may contribute to the cancer preventive effect. In the present study, the antitumor activity of noni was investigated in the presence of cyclophosphamide (CYL) in vitro and in vivo. METHODS: In vitro breast cancer cells (MDA-MB-468) were used to measure the percentage of inhibition and the IC50. The in vivo antitumor activity of noni was studied by monitoring the mean survival time (MST), percentage increase in life span (%ILS), viable and non-viable cell count, tumor volume, body weight, and hematological and serum biochemical parameters in mice. Treatment with noni and CYL exhibited dose- and time-dependent cytotoxicity toward breast cancer cells. RESULTS: Individual treatment of noni and CYL exhibited dose- and time-dependent cytotoxicity on breast cancer cell lines, while in combination therapy of noni and CYL, noni enhances cytotoxic effect of CYL at 48 h than that at 24 h. Similar result was found in in vivo studies, the results of which revealed that alone treatment of CYL and noni suppressed tumor growth. However, combination treatment with CYL and noni presented better tumor inhibition than that of alone treatment of CYL and noni. On the contrary, CYL alone drastically attenuated hematological parameters, i.e., RBC, WBC, and Hb compared to normal and control groups, and this change was reversed and normalized by noni when given as combination therapy with CYL. Moreover, the levels of serum biochemical markers, i.e., AST, ALP, and ALT, were significantly increased in the control and CYL-treated groups than those in the normal group. In the combination treatment of noni and CYL, the above biochemical marker levels significantly decreased compared to CYL alone-treated group. CONCLUSIONS: The present study suggested that CYL treatment can cause serious myelotoxicity and hepatic injury in cancer patients. In conclusion, the combined use of noni with CYL potentially enhances the antitumor activity of CYL and suppresses myelotoxicity and hepatotoxicity induced by CYL in tumor-bearing mice.

An insight into the cytotoxic, antimicrobial, antioxidant, and biocontrol perspective of novel Iron(III) complexes of substituted benzimidazoles: Inhibition kinetics and molecular simulations.

Mononuclear complexes [FeCl3L2(OH2)] (L = L1, L2) were designed and synthesized by combining FeCl3 with 2-(3'-Aminophenylbenzimidazole) (L1) and 2-[(3'-N-Salicylidinephenyl)benzimidazole] (L2) and were characterized by physico-analytical strategies. The redox properties of the complexes were disclosed by the cyclic voltammetric method. Further, the interactions of complexes with proteins were studied by performing molecular docking engaging protein models of common cancer therapeutic targets to foresee their affinity to bind to these proteins. The complexes evidenced better protein-ligand docking (-8.4 and -9.0 kcal mol-1) and higher binding energies than their ligands. However, the L1 complex displayed improved binding free energy (-33.576 ± 1.01 kcal mol-1) compared to the other complexes and individual ligands. These compounds were screened for in vitro cytotoxic assays against triple-negative breast cancer cell lines (MDA-MB-468 cells), anti-inflammatory, antimicrobial, and antioxidant properties. The in vitro study complemented the in silico assay; therefore, these compounds may be a viable choice for expanding anticancer therapy. Additionally, the L2 showed better biocontrol activity owing to the enhanced growth of Trichoderma and inhibited the growth of Fusarium oxysporum.Communicated by Ramaswamy H. Sarma.

Novel therapeutic targets to halt the progression of Parkinson's disease: an in-depth review on molecular signalling cascades.

Recent research has focused mostly on understanding and combating the neurodegenerative mechanisms and symptoms of Parkinson's disease (PD). Moreover, developing novel therapeutic targets to halt the progression of PD remains a key focus for researchers. As yet, no agents have been found to have unambiguous evidence of disease-modifying actions in PD. The primary objective of this review is to summarize the promising targets that have recently been uncovered which include histamine 4 receptors, beta2 adrenergic receptor, phosphodiesterase 4, sphingosine-1-phosphate receptor subtype 1, angiotensin receptors, high-mobility group box 1, rabphilin-3A, purinergic 2Y type 12 receptor, colony-stimulating factor-1 receptor, transient receptor potential vanilloid 4, alanine-serine-cysteine transporter 2, G protein-coupled oestrogen receptor, a mitochondrial antiviral signalling protein, glucocerebrosidase, indolamine-2,3-dioxygenase-1, soluble epoxy hydroxylase and dual specificity phosphatase 6. We have also reviewed the molecular signalling cascades of those novel targets which cause the initiation and progression of PD and gathered some emerging disease-modifying agents that could slow the progression of PD. These approaches will assist in the discovery of novel target molecules, for curing disease symptoms and may provide a glimmer of hope for the treatment of PD. As of now, there is no drug available that will completely prevent the progression of PD by inhibiting the pathogenesis involved in PD, and thus, the newer targets and their inhibitors or activators are the major focus for researchers to suppress PD symptomatology. And the major limitations of these targets are the lack of clinical data and less number pre-clinical data, as we have majorly discussed the different targets which all have well reported for other disease pathogenesis. Thus, finding the disease-drug interactions, the molecular mechanisms, and the major side effects will be major challenges for the researchers.

Four Togolese plant species exhibiting cytotoxicity and antitumor activities lightning polytherapy approach in cancer treatment.

Background: Cancer is leading to premature deaths across the globe. Therapeutic approaches are still being developed to enhance the survival of cancer patients. In our previous study, extracts from four Togolese plants, namely, Cochlospermum planchonii (CP), Piliostigma thonningii (PT), Paullinia pinnata (PP), and Securidaca longipedunculata (SL), actually used in traditional medicine for cancer treatment, showed beneficial health effects against oxidative stress, inflammation, and angiogenesis. Purpose: In the present study, we aimed to investigate the cytotoxicity and antitumor activities of these four plant extracts. Material and methods: Breast, lung, cervical, and liver cancer cell lines were exposed to the extracts, and viability was assessed using the Sulforhodamine B method. P. pinnata and S. longipedunculata with significant cytotoxicity were selected for in vivo tests. The acute oral toxicity of these extracts was assessed using BALB/c mice. The antitumor activity was evaluated using the EAC tumor bearing mice model, wherein mice were orally treated with extracts at different concentrations for 14 days. The standard drug was cisplatin (3.5 mg/kg, i.p), single dose. Results: Cytotoxicity tests revealed that SL, PP, and CP extracts have more than 50% cytotoxicity at 150 µg/mL. The acute oral toxicity of PP and SL at 2000 mg/kg did not show any toxic signs. At therapeutic doses of 100 mg/kg, 200 mg/kg and 400 mg/kg of PP and 40 mg/kg, 80 mg/kg, and 160 mg/kg of SL, extracts showed beneficial health effects by modulating several biological parameters. SL extract significantly reduced tumor volume (P < 0.001), cell viability, and normalized hematological parameters. SL also demonstrated a strong anti-inflammatory activity similar to the standard drug. The SL extract also revealed a significant increase of the life span of treated mice. PP extract reduced the tumor volume and significantly improved the values of endogenous antioxidants. Both PP and SL extracts also exerted significant anti-angiogenic potency. Conclusion: The study indicated that polytherapy would be a panacea for the efficient use of medicinal plant extracts against cancer. This approach will make it possible to act simultaneously on several biological parameters. Molecular studies of both extracts targeting key cancer genes in several cancer cells are currently underway.

Ultrasound-Guided Preoperative Fascia Iliaca Compartment Block for Pain Relief During Positioning for Spinal Anesthesia in Patients With Hip Fracture.

Background Fractures around the hip are common in the elderly. For surgical management, the subarachnoid block is the preferred anesthesia technique. Positioning these patients for anesthesia is challenging because of pain. Analgesia in the form of preoperative perineural anesthesia is gaining popularity. We observed the analgesic efficacy of preoperative ultrasound-guided fascia iliaca block, its efficacy during positioning for spinal anesthesia, pain scores, and anesthesiologist comfort while administering spinal anesthesia. Methodology An observational study was conducted on patients of 40 to 80 years under the American Society of Anesthesiologists (ASA) physical status I-III, requiring hip surgeries under spinal anesthesia. After pre-anesthetic evaluation, the purpose and protocol of the study were explained to patients, and informed consent was obtained. Pain score using the numeric rating scale (NRS) was recorded. Ultrasound-guided suprainguinal fascia iliaca block was performed using 30 ml of 0.25% levobupivacaine one hour before shifting to the operating room. Pain scores were reassessed. Spinal anesthesia was administered in the operating theatre in a sitting position. Pain during positioning was assessed. Results The mean NRS score reduced significantly after ultrasound-guided suprainguinal fascia iliaca block. The mean NRS score was 3.25 during positioning for spinal anesthesia compared to a pre-block score of 9.03, noting a statistically significant reduction (p=0.001). Conclusion Fascia Iliaca compartment block (FICB) helps alleviate the pain of hip fractures and makes positioning the subarachnoid block easier.

Novel dual PPARα/γ agonists protect against liver steatosis and improve insulin sensitivity while avoiding side effects.

Insulin resistance is a feature of type 2 diabetes mellitus (T2D), and is strongly interconnected with non-alcoholic fatty liver disease (NAFLD). Peroxisome-proliferator activated receptor gamma (PPARγ) and peroxisome-proliferator activated receptor alpha (PPARα) are master regulators of insulin sensitivity and lipid metabolism, respectively. Thiazolidinediones (TZDs) such as pioglitazone, which target PPARα/γ, are highly effective at treating insulin resistance and NAFLD, but their clinical utility has been restricted by side effects such as weight gain, adipocyte hypertrophy and fluid retention. Therefore, there is urgent need for new safer and effective drugs. Thus, we aimed to develop novel dual PPARα/γ agonists to avoid their known side effects while preserving their overall therapeutic effects. Here, we show that our novel agonists G4 and G5 strongly stimulate glucose transporter 4 (GLUT4) translocation to the cell membrane in skeletal muscle cells, and manifest weaker lipogenic effect in adipocytes. Moreover, G4 and G5 improve systemic glucose metabolism, hyperinsulinemia, hyperlipidemia, and markers of liver injury in high fructose diet-induced insulin resistant rats. Mechanistic studies revealed that G4 and G5 enhance GLUT4, and AMPK in skeletal muscle and protect against liver steatosis by upregulating PPARα and improve whole-body insulin sensitivity by increasing PPARγ. Despite this increase in PPARγ activity, G4 and G5 inhibit the unwanted side effects such as weight gain due to adiposity, hypertrophy of adipocytes, and fluid retention unlike TZDs. These findings identify G4 and G5 as promising dual PPARα/γ agonists for the treatment of NAFLD and insulin resistance with improved safety.

A telepathology based screening tool for COVID-19 by leveraging morphological changes related to leukocytes in peripheral blood smears.

As we approach the aftermath of a global pandemic caused by Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2), the importance of quickly developing rapid screening tests has become very clear from the point of view of containment and also saving lives. Here, we present an explorative study to develop a telepathology-based screening tool using peripheral blood smears (PBS) to identify Coronavirus Disease (COVID-19)-positive cases from a group of 138 patients with flu-like symptoms, consisting of 82 positive and 56 negative samples. Stained blood smear slides were imaged using an automated slide scanner (AI 100) and the images uploaded to the cloud were analyzed by a pathologist to generate semi-quantitative leukocyte morphology-related data. These telepathology data were compared with the data generated from manual microscopy of the same set of smear slides and also the same pathologist. Besides good correlation between the data from telepathology and manual microscopy, we were able to achieve a sensitivity and specificity of 0.83 and 0.71, respectively, for identifying positive and negative COVID-19 cases using a six-parameter combination associated with leukocyte morphology. The morphological features included plasmacytoid cells, neutrophil dysplastic promyelocyte, neutrophil blast-like cells, apoptotic cells, smudged neutrophil, and neutrophil-to-immature granulocyte ratio. Although Polymerase Chain Reaction (PCR) and antibody tests have a superior performance, the PBS-based telepathology tool presented here has the potential to be an interim screening tool in resource-limited settings in underdeveloped and developing countries.

Global Trends of Sunscreen Research Literature: A Bibliometric Analysis over the Period of 2010-2020.

Objective: To date, little effort has been devoted to summarizing worldwide research trends in sunscreen publications. The present study aimed to quantitatively analyze research trends in sunscreen publications over the past period from 2010 to 2020. Materials and Methods: The required bibliometric information was extracted and downloaded from the Scopus database. Documents including the keywords "Sunscreen" and "Sunscreens" were extracted from the database. A total of 1466 articles were retrieved from the database as on May 14, 2021. Data analysis and visualization were performed through RStudio. The bibliometrix package was accessed through the RStudio application to compute and process the bibliotec file. Results: Over the last decade (2010-2020), marked progress has been made in the area of sunscreens research. The overall increase in publications and citations reflects a growing research interest in the sunscreens field. The United States was the most prolific organization productive country with (n = 861) published documents, followed by Brazil (n = 273), Australia (n = 220), and France (n = 220). The most active institution was the Universidade Federal do Rio de Janeiro with publications (n = 30). Journal of the American Academy of Dermatology was the leading journal in the sunscreen literature with a total of (n = 55) documents. Conclusion: The main strength of the study is the use of the bibliometric analysis method and visualization of data to review the entire literature on sunscreens. The United States, Brazil, the United Kingdom, Australia, France, and China were active in most of the research parameters included in the study. These findings serve as a guide and road map for scholars in the field. This research can also be beneficial to academics, policymakers, and educational use.

Mitochondria-lysosome crosstalk in GBA1-associated Parkinson's disease.

Organelle crosstalk is significant in regulating their respective functions and subsequent cell fate. Mitochondria and lysosomes are amongst the essential organelles in maintaining cellular homeostasis. Mitochondria-lysosome connections, which may develop dynamically in the human neurons, have been identified as sites of bidirectional communication. Aberrancies are often associated with neurodegenerative disorders like Parkinson's disease (PD), suggesting the physical and functional link between these two organelles. PD is often linked with genetic mutations of several mutations discovered in the familial forms of the disease; some are considered risk factors. Many of these genes are either associated with mitochondrial function or belong to endo-lysosomal pathways. The recent investigations have indicated that neurons with mutant glucosylceramidase beta (GBA1) exhibit extended mitochondria-lysosome connections in individuals with PD. This may be due to impaired control of the untethering protein, which aids in the hydrolysis of Rab7 GTP required for contact untethering. A GCase modulator may be used to augment the reduced GBA1 lysosomal enzyme activity in the neurons of PD patients. This review focuses on how GBA1 mutation in PD is interlinked with mitochondria-lysosome (ML) crosstalk, exploring the pathways governing these interactions and mechanistically comprehending the mitochondrial and lysosomal miscommunication in the pathophysiology of PD. This review is based on the limited literature available on the topic and hence may be subject to bias in its views. Our estimates may be conservative and limited due to the lack of studies under the said discipline due to its inherent complex nature. The current association of GBA1 to PD pathogenesis is based on the limited scope of study and further research is necessary to explore the risk factors further and identify the relationship with more detail.

Correction: Calpain and Reactive Oxygen Species Targets Bax for Mitochondrial Permeabilisation and Caspase Activation in Zerumbone Induced Apoptosis.

[This corrects the article DOI: 10.1371/journal.pone.0059350.].

Assessment of Out of Pocket Expenditure and associated factors for availing COVID-19 vaccination by the beneficiaries in Bengaluru: South India

BackgroundGovernment of India has introduced COVID 19 vaccination in Jan 2021. There are no studies on out of pocket expenditure in COVID-19 vaccination in India, hence this study was undertaken to estimate the out of pocket expenditure for availing COVID 19 vaccine, to assess the factors associated with out of pocket expenditure for COVID vaccination and adverse events following immunisation. MethodsThis is a cross-sectional study conducted during Sep 2021-Dec 2021 of a medical college. A total of 438 study subjects above 18 years fulfilling inclusion and exclusion criteria were studied using probability proportional to population size. Data was collected using interview method by pre-tested semi structured proforma and analysed using descriptive & inferential statistics. ResultsThe mean direct cost in Government vaccination centre was 3.24{+/-} 6.74 INR, indirect cost 809.10{+/-}1076.35 INR, total cost was 812.34 {+/-}1079.49 INR.The mean direct cost in private vaccination centre was 1446.9{+/-}1845.65 INR, indirect cost 1140{+/-}1398 INR and total cost was 2586.90{+/-}2241.54 INR. The mean total cost was OOPE for COVID 19 vaccination was 852.80 {+/-}1128.512 INR, out of which direct cost was only 36.17({+/-}359.20). The higher mean OOPE was found in loss of wages 670.02 INR. The factors associated with higher out of pocket expenditure was type of vaccine (P=0.031, OR=2.141, 95% CI=1.07-4.24) occupation of the study subject (P=0.000, OR=2.043, 95% CI= 1.37-3.03), reported stress following vaccination (P= 0.018, OR=1.72, 95%CI=1.098-2.703), adverse event within 48hrs (P=0.006, OR=2.125, 95% CI= 1.248-3.62), received any medication for adverse event (P=0.041, OR= 1.721, 95% CI= 1.022-2.84) ConclusionMajority of the study subjects utilized public facility. The higher mean out of pocket expenditure was for indirect cost loss of wages. This study shows that type of vaccine, occupation of the study subject and adverse event within 48 hrs, had 2 times higher out of pocket expenditure compared to other factors. Among the AEFI, fever was the most common, followed by pain at the injection site and myalgia.

Ethnopharmacological evaluation of antioxidant, anti-angiogenic, and anti-inflammatory activity of some traditional medicinal plants used for treatment of cancer in Togo/Africa.

ETHNOPHARMACOLOGICAL RELEVANCE: Cancer is a multistep disease and its management is exceedingly expensive. Nowadays medicinal plants are gaining more attention in drug discovery and approximately 70% of anticancer drugs were developed from natural products or plants. A strong candidate from medicinal plant with anticancer potential should have four major properties: antioxidant, anti-inflammatory, anti-angiogenic, and cytotoxic activities. AIM OF THE STUDY: In order to assess Togolese traditional healer's claims about the anticancer potential of medicinal plants and obtain candidate plants for anticancer drug discovery, some species were selected from surveys and evaluated for their antioxidant, anti-inflammatory, anti-angiogenic and cytotoxic activities. METHODS: Four species, Cochlospermum planchonii (CP), Piliostigma thonningii (PT), Paullinia pinnata (PP), and Securidaca longipedunculata (SL) were selected and analyzed to detect the phytochemical components. The mentioned bioactivities were evaluated using in vitro, ex vivo and in vivo assays. RESULTS: Relative to SL extract, CP and PT have shown significantly high polyphenols and flavonoids content. The DPPH, FRAP, and TAC of the extracts revealed that CP, PT, and PP have a potent antioxidant effect compared to SL. MDA analysis revealed the same antioxidant activity as CP, PT and PP showed a minor MDA level. The egg albumin denaturation assay showed that IC50 of CP and PP was significantly higher than control (P < 0.05). In contrast, the Bovine Serum Albumin (BSA) results showed a nonsignificant effect (P > 0.05). Notably, SL extract was nonsignificant to control in both Egg Albumin and BSA. Furthermore, angiogenesis assay showed that SL at 50 µg/ml and PP at 100 µg/ml effectively reduced the number of blood vessels than control and showed a potent anti-angiogenic effect (2.7-fold and 2.5-fold, respectively, P < 0.05). No cytotoxicity on PBMC was reported for CP, PP, and PT up to 1000 µg/ml, whereas SL at 1000 µg/ml exhibit benign cytotoxicity (P < 0.0001). CONCLUSION: This study provided in vitro evidence supporting further evaluation on cancer cell lines and tumors in vivo.

Analysis of antimicrobial activity of Karnataka propolis against oral pathogens - An in vitro study.

Background: Propolis, a natural antibiotic, which is in high demand in dentistry is a resinous substance. The main ingredient of propolis that is required for antibiotic effect is flavonoids and phenolic acids. Although propolis is a promising option for the control of oral microbes with lower related hazards and a good immunomodulator effect, its composition differs considerably depending on its botanical origin, the site and the season of collection. This original research aims to find the chemical composition and minimum inhibitory concentration (MIC) of propolis procured from different places of Karnataka state. The results would help the dentist and the pharmacist to select the best propolis to use as antibiotics in treating oral disease. Materials and Methods: Propolis sample from 5 different locations of Karnataka was procured from single apiary in Bangalore. Extraction of propolis using two different extracting solvents was carried out. The total phenolic content, total flavonoid content and MIC of each sample were analyzed. Results: Water extract propolis of Sullia and Hubli was highly active against tested organism with the MIC <0.312; alcohol extract of Sullia, Hubli and Chitradurga was moderately active with the MIC between 0.312 and 5 mg/ml. Vijayapura and Bagalkot were least active with the MIC >5 mg/ml at tested concentration. Conclusion: Propolis procured from different locations of Karnataka can be used as an antimicrobial agent with varying concentrations. However, when propolis is procured for therapeutic purpose, then it needs to be tested for its chemical composition before being utilized.

Assessment of Healing Using Alvogyl and Platelet Rich Fibrin in Patients with Dry Socket - An Evaluative Study.

INTRODUCTION: Dry socket is one of the most common postoperative complications following the extraction of permanent teeth, which is characterized by pain and exposed bone. The usual protocol followed for its management is irrigation of the socket and packing of the socket with medicated gel or paste to provide relatively faster pain relief and allow normal wound healing. In this study, we evaluated the outcome of management of dry socket with platelet-rich fibrin (PRF) and intraalveolar alvogyl dressing, in terms of improvement in pain and socket epithelialization after the treatment. METHODOLOGY: Thirty participants with established dry socket were randomly divided into two groups: Group A and Group B. The participants in Group A were treated with alvogyl and those in Group B were treated with PRF. Clinical parameters were assessed for both groups on the 1st day of the procedure and on the 3rd and 10th-day postoperatively for the reduction in pain and wound healing. RESULTS: There was a significant decrease in pain and the number of socket wall exposure in both the groups by the 3rd postoperative day. In both the groups, the pain had completely resolved and socket fully epithelialized by the 10th postoperative day. DISCUSSION: The use of PRF in the present study yielded promising results in terms of both pain reduction and improved wound healing which was comparable to the conventional alvogyl dressing. It may be concluded that PRF is an effective modality for the management of dry socket.

Combined quantum mechanics/molecular mechanics (QM/MM) methods to understand the charge density distribution of estrogens in the active site of estrogen receptors.

The ligand binding to protein and host-guest interactions are ubiquitous for molecular recognition. In drug design, the ligand binding to the active site of proteins is influenced by the charge density distribution and the electrostatic interactions of ligands and the nearby amino acids of the protein. The charge density analyses of ligand-protein complexes need accurate positions of hydrogen atoms and their valence electron distribution and the fine structure of proteins. Such information cannot be obtained from the conventional protein X-ray crystallography analysis in the resolution range of 1.5 to 3.5 Å. This can be realized from QM/MM based structure and charge density analysis of estrogens with the estrogen receptor. The charge density properties such as electron density, Laplacian of electron density and electrostatic properties of estrogens in the presence of active site amino acid residues have been determined and compared with the isolated estrogen molecules from theory and experimental. The present study reveals the chemical bonding nature of estrogen molecules and the strength of the intermolecular interactions in the active site of estrogen receptor, and also the importance of π⋯π interactions between the estrogens and Phe404 amino acid residue and protonation state of His524 amino acid residue have been identified using electrostatic potential maps. The difference in the electrostatic potential map of estrogens displays the hormone dependent actions of estrogen receptor. This method is very helpful to derive the charge density distribution of macromolecules to understand their biological recognition and interactions.

Prophylactic preoperative levosimendan for off-pump coronary artery bypass grafting in patients with left ventricular dysfunction: Single-centered randomized prospective study.

BACKGROUND: Off-pump coronary artery bypass surgery (OPCAB) is often complicated by hemodynamic instability, especially in patients with prior left ventricular (LV) dysfunction and appropriate choice of inotrope plays a vital role in perioperative management of these patients. AIM AND OBJECTIVE: To study hemodynamic effects and immediate outcome of prophylactic infusion of levosimendan in patients with the LV dysfunction undergoing OPCAB surgery and whether this strategy helps in successful conduct of OPCAB surgery. MATERIALS AND METHODS: After Institutional Ethics Committee approval, 60 patients posted for elective OPCAB surgery were randomly divided into two groups (n = 30 each). Patients with the LV ejection fraction <30% were included. Study group was started on injection levosimendan (@ 0.1 µg/kg/min) in the previous night before surgery and continued for 24 h including intraoperative period. Hemodynamic monitoring included heart rate, invasive blood pressure, cardiac index (CI), pulmonary capillary wedge pressure (PCWP), pulse oximetry, and arterial blood gases with serum lactates at as T0 (baseline), T1 (15 min after obtuse marginal and/or PDA anastomoses), T2 (at end of surgery), T3 (6 h after surgery in Intensive Care Unit [ICU]), T4 (12 h after surgery), and T5 (24 h after surgery in ICU). Vasopressor was added to maintain mean arterial pressure >60 mmHg. Chi-square/Fisher's exact/Mid P exact test and Student's t-tests were applied for categorical and continuous data. RESULTS: CI was greater and PCWP reduced significantly in Group L during intraoperative and early postoperative period. Serum lactate concentration was lower in patients pretreated with levosimendan. Incidence of postoperative atrial fibrillation (POAF) (36.6 vs. 6.6%; P = 0.01), low cardiac output syndrome (LCOS) (30% vs. 6%; P = 0.02), and acute kidney injury (23.3% vs. 6.7%; P = 0.04) was less in Group L. Three patients (10%) in control group required conversion to cardiopulmonary bypass (CPB) as compared to none in the study group. There was no difference regarding ICU or hospital stay and mortality in both groups. CONCLUSION: Preoperative levosimendan helps in successful conduct of OPCAB and reduces the incidence of LCOS, POAF, conversion to CPB, and requirement of intra-aortic balloon pump.

Solanum nigrum Unripe fruit fraction attenuates Adriamycin resistance by down-regulating multi-drug resistance protein (Mdr)-1 through Jak-STAT pathway.

BACKGROUND: Solanum nigrum, herbal plant that commonly grows in temperate climate zone, has been used as a traditional folk medicine whose ripen fruits were proven to exhibit anti-tumor properties. In traditional Chinese medicine, it has been used for centuries to cure inflammation, edema, mastitis and hepatic cancer and in the Ayurvedic system of traditional medicine in India, S. nigrum is applied against enteric diseases, ulcer, diarrhea and skin diseases. A methanolic glycosidic extract fraction of unripe fruit of S. nigrum (SNME) was investigated for its anticancer property and possible mechanism to surmount adriamycin resistance in NCI/ADR-RES cells. METHODS: The NCI/ADR-RES cells were treated with 7.8125, 15.625, 31.25, 62.5, 125 and 250 µg/ml of methanolic extract of S. nigrum (SNME) for 12, 24 and 48 h, to check the cell viability and proliferation. The cells were also exposed to adriamycin alone or in combination with SNME and the effects on cell growth were determined by MTT. Cell cycle analysis, Ethidium bromide and Acridine orange staining, Annexin-binding efficiency, nuclear condensation and DNA fragmentation of the apoptotic NCI/ADR-RES cells were also determined. To elucidate the relationship between SNME and multi drug resistance, we analyzed the expression levels of Mdr-1, JAK1, STAT3, and pSTAT3 in NCI/ADR-RES cells after treatment with SNME. RESULTS: Results from the cytotoxicity assay showed a direct correlation between the concentration of methanolic glycosidic extract fraction of S. nigrum (SNME) and the surviving cell population. Combination with Adriamycin, SNME exhibits a synergistic action on NCI/ADR-RES cells, giving the first line of evidence to overcoming Adriamycin resistance. The SNME mediated cell growth suppression was proven to be apoptotic, based on results obtained from DNA fragmentation, annexin V apoptosis assaay and PARP cleavage analysis. Looking into the molecular insight SNME surpasses the chemoresistance of NCI/ADR-RES cells by inhibiting the JAK-STAT3 signaling pathway through the down regulation of JAK1, STAT3, pSTAT3, and Mdr1 expression. CONCLUSIONS: Collectively our findings suggest that unripe fruit of Solanum nigrum could possibly be used as a chemosensitizing agent against Adriamycin resistant cancers.

Conscious sedation using dexmedetomidine for percutaneous transcatheter closure of atrial septal defects: A single center experience.

OBJECTIVE: The aim of this study is to determine safety and feasibility of conscious sedation using dexmedetomidine for transcatheter atrial septal defect (ASD) device closure. MATERIAL AND METHODS: A retrospective institutional review of transcatheter ASD device closure without endotracheal intubation over 18 months. The protocol included topical oropharyngeal anesthesia using lignocaine followed by dexmedetomidine bolus 1 µg/kg intravenously over 10 min and maintenance dose 0.2-0.7 µg/kg/h. Ramsay sedation score 2-3 was maintained. Patients were analyzed regarding demographic profile, device size, procedure time, anesthesia time, recovery time, hospital stay, and any hemodynamic or procedural complications. RESULTS: A total of 43 patients with mean age 31.56 ± 13.74 years (range: 12-56 years) were analyzed. Mean anesthesia duration was 71.75 + 21.08 min. Mean recovery time was 7.6 ± 3.01 min. 16 females and one male patient required additional propofol with a mean dose of 30.8 ± 10.49 mg. No hemodynamic instability was noted. No patient required general anesthesia with endotracheal intubation. The procedure was successful in 93.02% of patients. Four patients developed atrial fibrillation. All patients were satisfied. CONCLUSION: Conscious sedation using dexmedetomidine is a safe and effective anesthetic technique for percutaneous ASD closure.

Cardioversion: What to choose? Etomidate or propofol.

CONTEXT: Electrical cardioversion is a short painful procedure to regain normal sinus rhythm requiring anaesthesia for haemodynamic stability, sedation, analgesia and early recovery. AIMS: To compare propofol and etomidate as sedatives during cardioversion. SETTINGS AND DESIGN: Single centred, prospective and randomized single blind study comprising 60 patients. SUBJECTS AND METHODS: Patients more than 18 years, American Society of Anesthesiologists I/II/III grades undergoing elective cardioversion, randomly divided to receive propofol 1 mg/kg intravenous (IV) bolus followed by 0.5 mg/kg (Group P, n = 30) or etomidate (Group E, n = 30) 0.1 mg/kg followed by 0.05 mg/kg. All patients received IV fentanyl (1 µg/kg) before procedure. Heart rate, blood pressure (BP) (systolic BP [SBP], diastolic BP [DBP], mean arterial pressure), respiratory rate, Aldrete recovery score (ARS) and Ramsay sedation score (RSS) were assessed at 1, 2, 5, 10, 15, 20 and 30 min post cardioversion. Incidence of hypotension, respiratory depression and side effects were compared. STATISTICAL ANALYSIS USED: Student's unpaired t-test, Chi-square test and Mann-Whitney test. P < 0.05 was taken as significant. RESULTS: Group P showed significant fall in SBP, DBP, and mean BP at 2 min after cardioversion. Hypotension (33.3% Group P vs. 16.65% Group E) occurred more with propofol (P < 0.05). Group E showed better ARS at 1, 2, 5, 10, 15 and 20 min. Time required to attain RSS = 2 (659.1 s Group P and 435.7 s Group E) indicated longer recovery with propofol. Left atrial size (35.5-42.5 mm) did not affect success rate of cardioversion (80% Group P vs. 83.3% Group E). Incidence of myoclonus (Group E 26.67% vs. Group P 0%) showed significant difference. CONCLUSIONS: Etomidate/fentanyl is superior over propofol/fentanyl during cardioversion for quick recovery and haemodynamic stability.