Synthesis of some new N-[alkyl/aralkyl]-N-[2,3-dihydro-1,4-benzodioxan-6-yl]-4-chlorobenzenesulfonamides as possible therapeutic agents for Alzheimer's disease and Type-2 Diabetes

In the current research work, a series of new N-[alkyl/aralkyl]-N-[2,3-dihydro-1,4-benzodioxan-6-yl]-4-chlorobenzenesulfonamides has been synthesized by reacting 1,4-benzozzdioxan-6-amine [1] with 4-chlorobenzenesulfonyl chloride [2] to yield N-[2,3-dihydro-1,4-benzodioxan-6-yl]-4-chlorobenzenesulfonamide [3] which was further reacted with different alkyl/aralkyl halides [4a-n] to afford the target compounds [5a-n]. Structures of the synthesized compounds were confirmed by IR, 1H-NMR, EI-MS spectral techniques and CHN analysis data. The results of enzyme inhibition showed that the molecules, N-2-phenethyl-N-[2,3-dihydro-1,4-benzodioxin-6-yl]-4- chlorobenzenesulfonamide [5j] and N-[1-butyl]-N-[2,3-dihydro-1,4-benzodioxin-6-yl]-4-chlorobenzenesulfonamide [5d], exhibited moderate inhibitory potential against acetylcholinesterase with IC50 values 26.25+/-0.11 ?M and 58.13+/-0.15 ?M respectively, whereas, compounds N-benzyl-N-[2,3-dihydro-1,4-benzodioxin-6-yl]-4-chlorobenzenesulfonamide [5i] and N-[pentane-2-yl]-N-[2,3-dihydro-1,4-benzodioxin-6-yl]-4-chlorobenzenesulfonamide [5f] showed moderate inhibition against ?-glucosidase enzyme as evident from IC50 values 74.52+/-0.07 and 83.52+/-0.08 µM respectively, relative to standards Eserine having IC50 value of 0.04+/-0.0001 µM for cholinesterases and Acarbose having IC50 value 38.25+/-0.12 µM for ?-glucosidase, respectively

Effect of caffeine on anti-clotting activity of warfarin in healthy male albino rabbits

Drug-drug interactions are most commonly occurring phenomenon in clinical practice. Many physicians are afraid of being involved in an allegation of malpractices due to the occurrence of any severe interaction. These interactions not only occur between drugs but also between any kind of food, tobacco smoke, caffeine and alcohol etc. Therefore, the present study was directed to inspect the effect of caffeine on the anticoagulation activity of warfarin in healthy adult male albino rabbits. Blank blood samples were collected from each rabbit. Rabbits were given warfarin [0.5mg kg-1] orally via stomach tube and blood samples were collected in PT/INR vials at various intervals. After a washout period of 14 days, warfarin was orally administrated at same dose rate along with caffeine [5 mg kg-1 every twelve hours for three days] and same sampling schedule was repeated. Prothrombin time [PT] and the international normalized ratio [INR] of blood samples were determined to estimate changes in the anticoagulation activity of warfarin after its concurrent administration with caffeine. The PT data revealed that Rmax and AUC increased significantly [P

Microbiological quality control of some non-sterile preparations commonly used in Pakistan

The quality of medicines in some developing countries including Pakistan is not very satisfactory regarding safety and efficacy. In addition to sterile preparations, the microbial contamination of non sterile preparations should also be monitored according to USP microbial limits for these preparations. This study was designed to check the microbial quality of some commonly used non-sterile preparations available in Pakistan. Total 133 samples containing national and multinational brands of different dosage forms were collected from retail setups of Sargodha, Khushab and Chakwal cities. The total aerobic bacterial count and fungal contamination was tested by pour plate method. The absence of objectionable microorganisms was confirmed by using selective media, biochemical testing and microscopy. Bioburden of these preparations was also tested after a storage period of six months. The bio burden varied among all the selected non-sterile preparations whether of local or multinational brands. The highest load was observed in syrups, among which syrup number 1 showed maximum aerobic count [8.4× 106]. Lowest count was observed in tablets, among which tablet preparation number 1 contained 1.5×103 aerobic bacteria. Creams and capsules produced no recovered bacteria. The fungal contaminants were also observed in all dosage forms except tablets. The isolated organisms included Gramnegative bacteria which contained objectionable ones such as Salmonella, Shigella, Pseudomonas and E.coli and some airborne moulds including Aspergillus spp., Penicillium spp., Fusarium spp. and Acremonium spp. Several measures such as GMPs, monitoring programs and SOPs should be followed by the pharmaceutical companies to reduce the microbial contamination level in the non sterile preparations. The regulatory agencies have to implement strict analysis strategy to check the microbial quality of the medicines before their release for sale in the market

2-[[5-(Substituted-phenyl]-1,3,4-oxadiazol-2-yl]sulfanyl]-N-[1,3-thiazol-2-yl]acetamides: new bi-heterocycles as possible therapeutic agents

An electrophile, N-[1,3-thiazol-2-yl]-2-bromoacetamide [3], was synthesized by the reaction of 1,3-thiazole-2- amine [1] and 2-bromoethanoyl bromide [2] in an aqueous medium. A series of carboxylic acids, 7a-j, were converted into 1,3,4-oxadiazole heterocyclic core, through a series of three steps. The final compounds, 8a-j, were synthesized by stirring 7a-j and 3 in an aprotic polar solvent. The structural elucidation of the synthesized compounds was supported by IR, EI-MS, 1 H-NMR, and 13C-NMR spectral data. Title compounds were evaluated for enzyme inhibition against cholinesterases and alpha-glucosidase enzymes and their cytotoxic behavior was monitored using brine shrimp assay. The enzyme inhibitor potential of compounds was supported by molecular docking studies

Conventional versus microwave assisted synthesis, molecular docking and enzyme inhibitory activities of new 3,4,5-trisubstituted-1,2,4- triazole analogues

N-[Substituted]-5-[1-[4-methoxyphenylsulfonyl]piperidin-4-yl]-4H-1,2,4-triazol-3-ylthio] acetamide were synthesized by following conventional as well as microwave assisted protocol through five consecutive steps under theimpact of various reaction conditions to control the reaction time and the yield of product. Starting from 4- methoxybenzenesulfonyl chloride and ethyl isonipecotate, product 3 was obtained which was converted into product 4by treating with hydrazine hydrate. In step 3, the product 4 was refluxed with methyl isothiocyanate and KOH to yield compound 5 which was finally treated with variety of N-substituted acetamides to yield an array of different new compounds [8a-k]. These synthesized compounds were evaluated for their inhibition potential against bovine carbonic anhydrase [bCA-II], acetylcholinesterase [AChE] and butyrylcholinesterase [BChE] enzymes. Compound 8g demonstrated good activity against bCA-II, AChE and BChE with IC50 values of 8.69 +/- 0.38 MuM, 11.87+/-0.19 MuM and 26.01+/-0.55 MuM respectively. SAR studies assisted with molecular docking were carried out to explore the mode of binding of the compounds against the studied enzymes

MicroRNAs: a new paradigm towards mechanistic insight of diseases

In 1993 miRNAs were discovered during a research on Caenorhabditis elegans conducted by Victor Ambros and Gary Ruvkun. The gene lin-4 that played important role in development in C. elgans was observed not encoding any protein but a very small RNA molecule of just 22 nucleotides. Main objective of this review is to highlight the significance of miRNAs in regulating the expression of many genes, which are either directly or indirectly involved in many diseases. One of the major causes of illness and death in developed countries of the world is cardiovascular disease. Some of the miRNAs have certain role to play in heart that are not specified for heart. So miRNAs have been found to be in other tissues like fibroblasts, endothelial cells and smooth muscle cells that are part of physiological study of cardiovascular system. Adult heart has limited capacity of regeneration therefore lost cardiomyocytes due to myocardial ischemia or infarction can result in low performance of heart. miRNAs have been shown to play a role in apoptotic regulation of cardiomyocytes in vivo. Many studies have shown that miR146a and 155 are up regulated in peripheral blood mononuclear cells, synovial fibroblasts, synovial fluid and Th-17 cells from rheumatoid arthritis patients as compared to healthy persons. Several types of miRNAs are playing important roles in type 1 diabetes mellitus including miR-375 and miR-375 with intolerance to glucose and decreased beta cells account due to impaired proliferation. Up regulation of miR-125a in WAT of type 2 Diabetes mellitus have been observed. miRNAs have proved to be the important regulators of cytokines and growth factor expression. Thus, suggested as a good biomarker and target of therapy. miRNA profiling techniques have revealed the role of miRNAs in Multiple sclerosis

Phytochemical analysis and antimicrobial activity of aqueous and methanolic extracts of the flowers of Nelumbium speciosum

In present investigation aqueous and methanolic extracts of Nelumbium speciosum flowers were screened for phytochemical constituents and antibacterial activity to ascertain their traditional use. Antimicrobial activity of both extracts was tested by Kirby-Bauer disc diffusion method against four Gram positive strains, viz. Staphylococcus aureus [ATCC25923], Streptococcus agalactiae [13813], Bacillus subtilis [ATCC 6633], Staphylococcus epidermidis [ATCC 12228] and four Gram negative bacterial strains Escherichia coli [ATCC 8739], Pseudomonas aeruginosa [ATCC 27853], Proteus mirabilis [12453] and Klebsiella pneumoniae [10031]. Phytochemical analysis showed the presence of tannins, saponins and alkaloids in both extracts while flavonoids and steroids were present only in methanolic extract. Methanolic extract of Nelumbium speciosum flower showed concentration dependent antibacterial activity against all tested strains with maximum zone of inhibition [17.3 +/- 0.3mm] against P. aeruginosa. Aqueous extract showed concentration dependent activity against S. aureus, E. coli, B. subtilis and S. epidermidis with maximum antibacterial activity against E. coli [14.3 +/- 0.3mm]. MIC of methanolic and aqueous extracts was in the range of 0.015-0.251 and 0.0625-0.251 mg/mL, respectively. Results showed that methanolic extract of Nelumbium speciosum exhibits superior antibacterial activity than aqueous extract

Synthesis, in vitro and in silico studies of S-alkylated 5-[4methoxyphenyl]-4-phenyl-4H-1, 2, 4-triazole-3-thiols as cholinesterase inhibitors

The research was aimed to unravel the enzymatic potential of sequentially transformed new triazoles by chemically converting 4-methoxybenzoic acid via Fischer's esterification to 4-methoxybenzoate which underwent hydrazinolysis and the corresponding hydrazide [1] was cyclized with phenyl isothiocyanate [2] via 2-[4methoxybenzoyl]-N-phenylhydrazinecarbothioamide [3]; an intermediate to 5-[4-methoxyphenyl]-4-phenyl-4H-1,2,4triazol-3-thiol [4]. The electrophiles; alkyl halides 5[a-g] were further reacted with nucleophilic S-atom to attain a series of S-alkylated 5-[4-methoxyphenyl]-4-phenyl-4H-1,2,4-triazole-3-thiols 6[a-g]. Characterization of synthesized compounds was accomplished by contemporary spectral techniques such as FT-IR, 1H-NMR, 13C-NMR and EI-MS. Excellent cholinesterase inhibitory potential was portrayed by 3-[n-heptylthio]-5-[4-methoxyphenyl]-4-phenyl-4H-1,2,4triazole; 6g against AChE [IC50; 38.35 +/- 0.62?M] and BChE [IC50; 147.75 +/- 0.67micro M] enzymes. Eserine [IC50; 0.04 +/- 0.01?M] was used as reference standard. Anti-proliferative activity results ascertained that derivative encompassing long straight chain substituted at S-atom of the moiety was the most potent with 4.96 % cell viability [6g] at 25 micro M and with 2.41% cell viability at 50?M among library of synthesized derivatives. In silico analysis also substantiated the bioactivity statistics

Frequency of nasal carriage of Staphylococcus Aureus among health care workers at a Tertiary Care Hospital

Objective: To determine the frequency of Methicillin resistance staphylococcus aureus [MRSA] and identification of drug susceptibility for MRSA isolates among health care workers [HCWs] of a tertiary care hospital of South Punjab Pakistan

Methods: We included 225 HCWs including laboratory staff, doctors, nurses and paramedical staff in this cross-sectional study. The study was conducted in Nishtar medical university/Hospital Multan. The study duration was July-2016 to April-2017. HCWs having no signs of infections and any other systemic disease were included in this study. We used sterile nasal swab sticks for sample collection for determination of S. aureus prevalence. All these samples were processed in the laboratory for MRSA, methicillin sensitive S. aureus (MSSA) and for antimicrobial sensitivity of S. aureus. Chi-square test was used for comparison of frequency of MRSA and MSSA between different HCWs by assuming p-Value

Results: There were 65.3 percent [147] female participants and only 34.7 percent [78] male participants. S. aureus was diagnosed in the nasal flora of 24 percent [54] participants, out of which 9.3 percent [21] were MRSA positive and remaining 14.7 percent [33] were MSSA positive. There was no significant difference in frequency of MRSA and MSSA among different HCWs [p-value 0.79]. Amikacin and vancomycin were 100 percent sensitive for MRSA and MSSA. Clindamycin and ciprofloxacin was 80.9 percent [17] and 71.4 percent [15] sensitive for MRSA and 100 percent and 84.8 percent [28] for MSSA respectively. While oxacillin and Cefoxitin were 100 percent [21] resistant for MRSA and sensitive for MSSA

Conclusion: Prevalence of MRSA and MSSA is high among HCWs in Pakistan. Amikacin, vancomycin and clindamycin have high sensitivity for MRSA and can be used for empirical treatment of MRSA in suspected patients

Prevalence of Hypogonadism in males of different age groups: is it a lack of awareness?

Introduction: Hypogonadism in aging male is defined as [Syndrome caused by androgen deficiency which affect multiple organ functions and qualityof life]. Patients present with different symptoms like male erectile dysfunction, decreased sexual desire, anemia etc.

Objectives: To demonstrate the serum testosterone levels and prevalence of hypogonadism in different age groups and their correlation with symptoms of hypogonadism

Study Design: Cross sectional comparative study

Settings: Allied Hospital Faisalabad. Duration: 3 years and 6 months, from Dec 1, 2015 to May 30, 2018

Methodology: 180 healthy looking males were randomly taken from attendants of patients of Urology Department from indoor or from OPD and categorized into six groups according to their age decades: starting from Group-I [20-29 years] and ending at Group 6 [70 years and above]. Informed consent was taken. Symptoms of every person were recorded on Aging male symptoms scale [AMS]proforma/questionnaire. BMI, testicular volume,serum testosterone, Albumin, estradiol, SHBG, HbA1c and Blood Sugar were recorded. Results were recorded and put in SPSS version 10 for statistical analysis

Results: Average serum testosterone of different groups was 9.43+/-2.7ng/ml. The study shows a decrease in average serum testosterone level by 28.95 percent with advancing age. This difference is statistically not significant [chi square test, p-value 0.554]. The prevalence of hypogonadism was 10 percent in advanced age groups of our study population and all persons having low testosterone were symptomatic. Study showed93.44percentincrease in the severity of symptoms with advancing age

Conclusion: Serum testosterone falls with advancing age leading to differentsymptoms of hypogonadism but it is under reported as none of the persons was aware of this problem

Drug induced acute kidney injury: an experimental animal study

Objective: To assess the extent of drug induced nephrotoxicity in laboratory animals for determining the role and extent of iatrogenic kidney damage in patients exposed to nephrotoxic drugs in various clinical setups

Study Design: Randomized control trail

Place and Duration of study: Pharmacology department and animal house of Army Medical College from Jan 2011 to Aug 2011

Material and Methods: Thirty six mixed breed rabbits were used in this study. Animals were randomly divided into six groups consisting of six rabbits in each. Groups were named A, B, C, D, E and F. Group A was control group. Group B was given 0.9% normal saline. Group C rabbits were given acute nephrotoxic single dose of amphotericin B deoxycholate. Group D received 0.9% normal saline 10ml/kg followed by amphotericin B infusion. Group E was injected acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Group F received saline loading along with acute nephrotoxic regimen of cyclosporine and amphotericin B infusion

Results: Biochemical and histopathological analysis showed significant kidney injury in rabbits exposed to acute nephrotoxic doses of amphotericin B and cyclosporine. Toxicity was additive when the two drugs were administered simultaneously. Group of rabbits with saline loading had significantly lesser kidney damage

Conclusion: Iatrogenic acute kidney damage is a major cause of morbidity in experimental animals exposed to such nephrotoxic drugs like amphotericin B and cyclosporine, used either alone or in combination. Clinical studies are recommended to assess the extent of iatrogenic renal damage in patients and its economic burden. Efficient and cost effective protective measure may be adopted in clinical setups against such adverse effects

Hematologic adverse effects and efficacy monitoring in chronic Hepatitis C patients treated with interferon and ribavirin combination therapy

180 million people are affected by chronic Hepatitis C Virus infection globally and more than 50 million in South East Asia. Combination of Interferon and Ribavirin is the current anti-HCV therapy in practice and is associated with certain hematologic adverse effects. In this concurrent observational study the incidence rate of major hematologic adverse effects and efficacy outcomes of Interferon and Ribavirin combination therapy was evaluated in 288 chronic hepatitis C patients at Lahore General Hospital. Levels of Hb, TLC, and Platelets counts were monitored for hematologic adverse effects monitoring, whereas, ALT, AST and bilirubin levels were monitored for efficacy. PCR was done at week 4, 12 and 36 for therapeutic success evaluation. A significant reduction in Hb levels [p<0.05] was observed after week 4, 8 and 12 of therapy. Frequency of anemia increased in both genders with body weight <65kg and platelet count <150,000/mm3. End Treatment Response [ETR] was achieved in 64.5%. Anemia was the major side effect of the combination therapy particularly in the males. Higher ETR was observed in patients who achieved RVR and were <50 years of age

Enzyme inhibitory, antifungal, antibacterial and hemolytic potential of various fractions of Colebrookia oppositifolia

The purpose of the present investigation was to assess the enzyme inhibition, antifungal, antibacterial and hemolytic activities of various fractions of Colebrookia oppositifolia Smith. The MeOH extract of plant was dissolved in dist. water and partitioned with n-hexane, CHCl[3], EtOAc and n-BuOH sequentially. Enzyme inhibition studies were done against four enzymes i.e. alpha-glucosidase, butyrylcholinesterase, acetyl cholinesterase and lipoxygenase. Ethyl acetate fraction possessed very good activity against alpha-glucosidase [IC[50] 57.38 +/- 1.23 micro g/mL]. CHCl3 fraction displayed good activity against alpha-glucosidase and lipoxygenase while moderate activity against butyryl cholinesterase. EtOAc fraction displayed good activity against lipoxygenase. Antifungal activity was studied against four fungi i.e. Aspergillus niger, Aspergillus flavus, Ganoderma lucidum and Alternaria alternata by the disc diffusion method using fluconazole, a standard antifungal drug, as positive control. Aqueous fraction displayed good activity against G. lucidum and A. flavus. Antibacterial activity was checked against Staphylococcus aureus, Bacillus subtilis, Pasturella multocida and Escherichia coli by the disc diffusion method using streptomycin sulphate, a standard antibiotic, as positive control. Chloroform, ethyl acetate and aqueous fraction showed good activity against E. coli. Chloroform fraction showed good activity against B. subtilis. Ethyl acetate fraction showed good activity against the P. multocida. All the studied fractions showed very less toxicity i.e. < 7%

Determination of nitrate in biological fluids by HPLC

Nitrate is the stable product of nitric oxide, which is physiologically active radical, an immunomodulator and a neuromodulator; its quantification in biological fluids is important to study the physiological and biochemical nature. Therefore, the purpose of this study was to quantify nitrate in different biological fluids like serum, cerebrospinal fluid [CSF] and ascetic fluid [ASF] using HPLC technique. A new HPLC method for the estimation of nitrate in serum, CSF and ASF was developed using the mobile phase of 1.0mM each of Na[2]CO[3] and NaHCO3 [1:1, v/v, pH 5 with H[3]PO[4]] at a flow rate of 1.0mLmin[-1]. Eluate was detected at 220nm with the retention time of nitrate 2.55 min. The LOD and LOQ values of nitrate were 0.03 micro gmL[-1] and 0.098 micro gmL[-1], respectively. Nitrate was eluted through SAX Hypersil column of 150 x 4.6mm, id, 5 micro m particle size. Run time was 10min. The method was validated according to the FDA guidelines and was found linear in the range of 0.39 to 50 micro gmL[-1] and CV was <3%, within limits of FDA guidelines. The method was used successfully for the estimation of nitrate in biological fluids like serum, CSF and ASF of 20 patients each. This is an alternate and reproducible method for the detection of nitrates in biological fluids

Pharmacokinetic behavior of montelukast in indigenous healthy male volunteers

Aim of present study was to investigate the pharmacokinetic behavior of Montelukast in the healthy male volunteers under indigenous conditions. One tablet of montelukast 10 mg was administered in each subject and blood at different time intervals. Concentration of montelukast in plasma samples was analyzed by high performance liquid chromatography method to calculate pharmacokinetic parameters. The plasma concentration of montelukast was in the range of 1.31-1.76 micro g/mL at 0.5-12 hours with C[max] value of 1.59+/-0.16 micro g/mL at 3.71+/-0.64 hours. These values of plasma drug concentrations were above the minimum effective concentration of montelukast during the entire study hours. Absorption and elimination half-lives of the montelukast were evaluated as 2.52+/-0.54 hours and 2.63+/-0.35 hours, respectively. The volume of distribution and total body clearance of montelukast were investigated as 0.34+/-0.01 L/kg and 0.01+/-0.00 L/hr/kg, respectively. The pharmacokinetic parameters i.e. Cmax, AUC, t1/2, Vd and ClB of montelukast calculated in present study were found different as compared to that of the previous literature values which was due to genetic and environmental variation

Faith healing options among children having illness

Background: Faith healing among parents having children with illness still continues

Objective: To determine the frequency of different faith bassed modes of treatment of childhood diseases

Methodology: Study Design: Cross sectional study

Setting: Pediatrics Department, Nawaz Sharif Medical College and Doctors Hospital, Gujrat, Pakistan. 480 children admitted in pediatric ward were included from 1[st] April 2014 to 31[st] March 2016. Variables included in study were age, age, sex, current illness, any faith healing opted like, manat, visit to shrine and animal sacrifice. The data was entered and analyzed by SPSS version 16

Results: A total of 480 children were included with 310 [64.58%] were female whereas 170 [35.42%] were male. 360 children [75%] were from rural areas of Gujrat whereas 120 [25%] were from urban area. Different modes of treatment were availed

Conclusion: Our study showed that faith healing among children with illness was high and most of the parents "Visited Shrine" and "Manat" to heal the disease. Health education to increase the awareness may help in early diagnosis and treatment

Clinical profile and short-term outcome of pediatric hyperleukocytic acute leukemia from a developing country

This study was conducted to determine the frequency, clinical profile, and short-term outcome of children with hyperleukocytosis at two pediatric oncology centers in Karachi. Of a total 1,045 patients, 13.97% [n=146] patients had hyperleukocytosis. Majority [61.7%, n=90] were under 10 years of age and 76% [n=146] were male. The symptom duration before diagnosis was more than 30 days in 49.3% [n=72]. The median WBC count was 181 x109/L [IQR=130.45- 298.3] and extreme hyperleukocytosis [>200 x109/L] was observed in 44.5% [n=65] patients. Majority [94.5%, n=138] of patients were diagnosed with acute lymphoblastic leukemia. One or more complications developed in 78% [n=114] of cases. Clinical and laboratory tumor lysis syndrome [TLS] was observed in 17.1% [n=25] and 39% [n=57] patients, respectively. Pulmonary and neurological complications related to leukostasis were noted in 9.5% [n=14] and 27.3% [n=40] of cases, respectively. Infectious complications occurred in 23.2% [n=34] patients. The case-specific mortality was 20.5% [n=30]. No mortality was related to early complications of hyperleukocytosis

Impact of different treatment modalities on the outcome of pancreatic cancer

Objective: To analyze overall survival patterns of our pancreatic cancer patient population managed with a curative or palliative intent

Study Design: Analytical study

Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from January 2000 till February 2015

Methodology: A retrospective review of the data of all of our pancreatic cancer patients was performed, using the hospital information system. Patients with tumor other than adenocarcinoma or a histopathologic diagnosis not made at our hospital are excluded from the study, along with patients having an incomplete medical record for all included variables. The main outcome measure was overall survival in months from the date of diagnosis. All results were segregated and analyzed according to the intervention modality used, i.e. group A: surgery with curative intent, group B: Palliative chemotherapy, and group C: Supportive care. Results were controlled for the confounding variables including age, gender, significant comorbid conditions, stage of disease at initial presentation, tumor location, and histological grade

Results: Among the 197 patients fulfilling the inclusion criteria, 21 [10.7%] were excluded as they were lost to follow-up. Overall Kaplan-Meier survival analysis gave a 56% one-year survival, 22% at 3- and 16% at 5-year. The subset analysis on Cox-regression survival plot showed inferior survival with advancing stage of the disease and a treatment less than definitive surgical resection and adjuvant chemotherapy. On Cox-proportional regression analysis, stage of the disease and treatment modality were only independent predictive factors for overall survival [p < 0.01]

Conclusion: Stage for stage, surgery with curative intent [group A] or palliative chemotherapy [group B] showed a trend towards improved survival as compared to supportive management [group C] alone. The results were more significant for surgical resection arm

Burr hole aspiration of brain abscess in children with cyanotic heart disease

Objective: To determine the efficacy of burr hole aspiration of brain abscess in children with cyanotic heart disease in terms of number of aspirations and residual abscess

Study Design: Experimental study

Place and Duration of Study: Department of Pediatric Neurosurgery at The Children's Hospital and The Institute of Child Health, Multan, from July 2010 to June 2014

Methodology: Pediatric patients of cyanotic heart disease with brain abscess were admitted. After taking history, clinical examination and necessary investigation, aspiration of abscess through a burr hole was performed. Data was collected through pre-designed proforma. Analysis of results was performed and comparison was made through statistical package for social sciences [SPSS-20]

Results: Total number of patients were 50 with 31 [62%] male and 19 [38%] female children. Patients' age ranged from 5-10 years with mean age of 7.44 +/-1.11 years. Single abscess in supra tentorial was commonly found in 44 [88%] patients. Multiple abscesses were present in 4 [8%] patients. Cerebellum was involved in 2 [4%] patients. Abscess was completely aspirated in single attempt in 37 [74%] patients, two attempts in 9 [18%] patients, and three attempts in 4 [8%] patients. No bacterial growth on culture was reported in 32 [64%] patients. Culture was positive in 18 [36%] patients. Postoperative hematoma developed in 2 [4%] patients. No mortality was reported in early postoperative period

Conclusion: Aspiration of brain abscess in children with cyanotic heart disease through a burr hole is safe and successful

Synthesis, pharmacological screening and computational analysis of some 2-[l-Indol-3-yl]-A [[un]substituted phenylmethylidene] acetohydrazides and 2-[l-Indol-3-yl]-7V[[un]substituted benzoyl/2-thienylcarbonyl] acetohydrazides

The undertaken research was initiated by transforming 2-[l-Indol-3-yl]acetic acid [1] in catalytic amount of sulfuric acid and ethanol to ethyl 2-[l-Indol-3-yl]acetate [2], which was then reacted with hydrazine monohydrate in methanol to form 2-[l-Indol-3-yl]acetohydrazide [3]. Further, The reaction scheme was designed into two pathways where, first pathway involved The reaction of 3 with substituted aromatic aldehydes [4a-o] in methanol with few drops of glacial acetic acid to generate 2-[l-Indol-3-yl]-AD-[[un]substitutedphenylmethylidene]acetohydrazides [5a-o] and in second pathway 3 was reacted with acyl halides [6a-e] in basic aqueous medium [pH 9-10] to afford 2-[l-Indol-3-yl]-AD-[[un]substitutedbenzoyl/2-thienylcarbonyl]acetohydrazides [7a-e]. All The synthesized derivatives were characterized by IR, EI-MS and !H-NMR spectral techniques and evaluated for their anti-bacterial potentials against Gram positive and Gram negative bacterial strains and it was found that compounds 7a-d exhibited antibacterial activities very close to standard Ciprofloxacin. The synthesized derivatives demonstrated moderate to weak anti-enzymatic potential against oc-Glucosidase and Butyrylcholinesterase [BChE] where, compounds 7c and 5c exhibited comparatively better inhibition against these enzymes respectively. Compounds 7a, 7d and 7e showed excellent anti-enzymatic potentials against Lipoxygenase [LOX] and their IC[5]o values were much lower than the reference standard Baicalein. Enzyme inhibitory activities were also supported by computational docking results. Compounds 5c, 7a, 7b and 7c also showed low values of % hemolytic activity as well, showing that these molecules were not toxic, indicating that these molecules can be utilized as potential therapeutic agents against inflammatory ailments