Antinociceptive, anti-inflammatory and anti-diarrheal activities of the hydroalcoholic extract of Lasia spinosa Linn. (Araceae) Roots

Various parts of Lasia spinosa (Linn.) are widely used in many Asian countries to manage a wide range of diseases but so far no scientific study was done to find out its pharmacological properties which may support its uses in traditional medicine. The present study was carried out to evaluate the possible anti-nociceptive, anti-inflammatory, and anti-diarrheal activities of hydroalcoholic extract of root of Lasia spinosa in rodents. Anti-nociceptive activity was investigated using acetic acid-induced writhing and hot plate-induced pain in mice; anti-inflammatory activity using carrageenan-induced paw edema model rats and xylene-induced ear edema mice and anti-diarrheal activity using castor oil-induced diarrhea model mice. In acetic acid-induced writhing model mice, the extract caused a maximum of 50 % (p -1 body weight, which was comparable with standard drug, diclofenac sodium 60.71 % (p -1 and at 500 mg kg-1 also significantly increased pain threshold in hot-plate method in a dose dependent manner compared to the standard drug, nalbuphine. A dose dependent significant inhibitory effect on edema formation was found in xylene-induced ear edema model mice [17.0 5% at 250 mg kg-1 (p -1 (p -1 (p -1 (p < 0.001)]. In case of castor oil-induced diarrheal mice model, both standard drug (loperamide) and extract significantly reduced the number of stools and enhanced the latent period of diarrhea induction dose dependently. These findings indicate that the extract has significant anti-nociceptive, anti-inflammatory, and also antidiarrheal activity that supports its use in traditional medicine.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Antinociceptive, anti-inflammatory and anti-diarrheal activities of the hydroalcoholic extract of Lasia spinosa Linn. (Araceae) Roots

Various parts of Lasia spinosa (Linn.) are widely used in many Asian countries to manage a wide range of diseases but so far no scientific study was done to find out its pharmacological properties which may support its uses in traditional medicine. The present study was carried out to evaluate the possible anti-nociceptive, anti-inflammatory, and anti-diarrheal activities of hydroalcoholic extract of root of Lasia spinosa in rodents. Anti-nociceptive activity was investigated using acetic acid-induced writhing and hot plate-induced pain in mice; anti-inflammatory activity using carrageenan-induced paw edema model rats and xylene-induced ear edema mice and anti-diarrheal activity using castor oil-induced diarrhea model mice. In acetic acid-induced writhing model mice, the extract caused a maximum of 50 % (p -1 body weight, which was comparable with standard drug, diclofenac sodium 60.71 % (p -1 and at 500 mg kg-1 also significantly increased pain threshold in hot-plate method in a dose dependent manner compared to the standard drug, nalbuphine. A dose dependent significant inhibitory effect on edema formation was found in xylene-induced ear edema model mice [17.0 5% at 250 mg kg-1 (p -1 (p -1 (p -1 (p < 0.001)]. In case of castor oil-induced diarrheal mice model, both standard drug (loperamide) and extract significantly reduced the number of stools and enhanced the latent period of diarrhea induction dose dependently. These findings indicate that the extract has significant anti-nociceptive, anti-inflammatory, and also antidiarrheal activity that supports its use in traditional medicine.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Phenotype-based drug screening reveals association between venetoclax response and differentiation stage in acute myeloid leukemia

Ex vivo drug testing is a promising approach to identify novel treatment strategies for acute myeloid leukemia (AML). However, accurate blast- specific drug responses cannot be measured with homogeneous "add-mix-measure" cell viability assays. In this study, we implemented a flow cytometry-based approach to simultaneously evaluate the ex vivo sensitivity of different cell populations in 34 primary AML samples to seven drugs and 27 rational drug combinations. Our data demonstrate that different cell populations present in AML samples have distinct sensitivity to targeted therapies. Particularly, blast cells of FAB M0/1 AML showed high sensitivity to venetoclax. In contrast, differentiated monocytic cells abundantly present in M4/5 subtypes showed resistance to Bcl-2 inhibition, whereas immature blasts in the same samples were sensitive, highlighting the importance of blast-specific readouts. Accordingly, in the total mononuclear cell fraction the highest BCL2/MCL1 gene expression ratio was observed in M0/1 and the lowest in M4/5 AML. Of the seven tested drugs, venetoclax had the highest blast-specific toxicity, and combining venetoclax with either MEK inhibitor trametinib or JAK inhibitor ruxolitinib effectively targeted all venetoclax-resistant blasts. In conclusion, we show that ex vivo efficacy of targeted agents and particularly Bcl-2 inhibitor venetoclax is influenced by the cell type, and accurate blast-specific drug responses can be assessed with a flow cytometry-based approach.Peer reviewe

Development of High Throughput Flowcytometric Assay for Immunophenotypical Quantification of Leukemic Stem Cells and Phenotype Based Drug Sensitivity Approach in Acute Myeloid Leukemia

There is significant reduction in number of approved drugs for acute myeloid leukemia in recent years. Partially it may be due to the failure of discovery and validation approach to new drugs as well as the complexity of the disease. Ex vivo functional drug testing is a promising approach to identify novel treatment strategies for acute myeloid leukemia (AML). In ideal condition, an effective drug should eradicate the immature AML blasts, but spare non-malignant hematopoietic cells. However, current strategies like conventional cell viability assay fail to measure cell population-specific drug responses. Hence, development of more advanced approaches is needed. Using multiparameter, high-content flow cytometry (FC), we simultaneously evaluated the ex vivo sensitivity of different cell populations in multiple (10) primary AML samples to 7 FDA/EMA-approved drugs and 8 drug combinations. Amongst the 7 tested drugs, venetoclax, cytarabine and dasatinib were very cytotoxic with venetoclax had the highest blast-specific toxicity, and combining cytarabine with JAK inhibitor ruxolitinib effectively targeted all leukemic blasts but spared non-malignant hematopoietic cells. Taken together, we show that the ex vivo efficacy of targeted agents for specific AML cell population can be assessed with a cell phenotype, FC-based approach. Furthermore, we put an effort to analyze the potential of this assay and biomarkers to predict the clinical outcome of individual patients and future perspectives

Sigmoid Colonic Perforation with Faecal Peritonitis due to Faecaloma

Colon perforation is an uncommon event usually caused by malignancy, diverticular disease, amoebic colitis, steroid therapy, trauma and ulcerative colitis, but stercoral perforation is very rare. Severe chronic constipation is considered to be the main causative factor in development of stercoral perforation of colon. Sometimes it can also produce catastrophic complications like colonic obstruction, faecal peritonitis and septicaemia. We report a rare case of sigmoid colonic perforation with faecal peritonitis and pneumoperitonium due to faecaloma which was diagnosed after exploratory laparotomy

Comparative Study between Slow Shock Wave Lithotripsy and Fast Shock Wave Lithotripsy in the Management of Renal Stone

Background: Renal calculi are frequent causes of ureteric colic. Extracorporeal shock wave lithotripsy is the most common treatment of these stones. It uses focused sound waves to break up stones externally. Objective: To compare the efficiency of slow and fast delivery rate of shock waves on stone fragmentation and treatment outcome in patients with renal calculi. Materials and Methods: This prospective study was done in the department of Urology, National Institute of Kidney diseases and Urology, Sher-e-Bangla Nagar, Dhaka from July 2006 to June 2007. Total 90 patients were treated using the Storz Medical Modulith ® SLX lithotripter. Patients were divided into Group A, Group B and Group C – each group having 30 subjects. Group A was selected for extracorporeal shockwave lithotripsy (ESWL) by 60 shock waves per minute, Group B by 90 shock waves per minute and Group C by 120 shock waves per minute. Results: Complete clearance of stone was observed in 24 patients in Group A and 13 patients in both Group B and Group C in first session. In Group A only 3 patients needed second session but in Group B and Group C, 12 and 8 patients needed second session. In Group A only one patient needed third session but third session was required for 3 patients in Group B and 5 patients in Group C for complete clearance of stone. In Group A, subsequent sessions were performed under spinal anesthesia and in Group B under sedation and analgesia (p>0.001). Mean number of sessions for full clearance of stones in group A was 1.37 ± 0.85, in Group B was 1.8 ± 0.887 and in Group C was 2.0 ± 1.083. Significant difference was observed in term of sessions among groups (p>0.05). In first follow-up, complete clearance of stones was seen in 24 patients in Group A and 13 in both Group B and Group C. In second follow-up, 3 patients in Group A, 12 in Group B and 8 in Group C showed complete clearance of stones. It was observed that rate of stone clearance was higher in Group A than in Group B and Group C. Multiple logistic regression analyses revealed that slow delivery rate (60 SW/min) as well as age (younger), symptom (painful) at onset, stone location (upper and middle calyx) and size (small) were independent prognostic factors determining stone clearance after ESWL of renal stone. Conclusion: Slow rate shock wave delivery improves efficacy of ESWL treatments of renal stone and decreased number of sessions, shock waves and treatment time