Thiosemicarbazone and thiazolylhydrazones of 1-indanone: as a new class of nonacidic anti-inflammatory and antiplatelet aggregation agents

This research based on the anti-inflammatory and antiplatelet aggregation properties of some new thiazolyl hydrazone derivatives of 1-indanone. In this regard a thiosemicabazone and twelve thiazolyl derivatives of 1-indanone have been synthesized. Out of these synthetic compounds seven derivatives 1-3, 6, 11-13 exhibited varying degree of anti-inflammatory action with IC50 esteems going from 5.1+/-1.3 - 78.8+/-4.6µM/mL. Compound 1 [IC50 =5.1+/-1.9µM] displayed potent result than standard ibuprofen [IC50 = 11.2+/-1.9 µM]. In antiplatelet aggregation assay, five compounds 1, 5, 6, 8 and 11 were observed to be dynamic with IC50 esteems observed in the range of 38.34-255.7+/-4.1µM, whereas, aspirin [IC50 = 30.3+/-2.6 µM] was used as standard. However, compound 11 was found to be good active for both anti-inflammatory and antiplatelet aggregation activities [IC50 = 13.9+/-4.9µg/mL] [IC50 = 38.60+/-3.1µM], respectively

Synthesis of drug metal complexes and their influence on human platelet aggregation

During the past few decades the emergence of inorganic medicinal chemistry has been developed novel therapeutic agents. Researcher's perseverance in this branch of chemistry has led them to explore further valuable chemical spaces by synthesizing metal complexes already known pharmacological agents for their potential use. However, it is in its early stage, this methodology has demonstrated metal complexes with better bioactivities than the parent ligand molecules. In this study, transition metal complexes of pyrazinamide [PZ], isoniazid [INH], fluconazole [FCZ], metformin [dimethylbiguanide, DMBG] and losartan potassium [LS-K] were selected to evaluate for their possible anti-platelets aggregation in the light of reports on divalent and trivalent cations like calcium, copper, manganese, magnesium, and cadmium may influence the process of thrombocytic activity and aggregation. The required evaluation was carried out on human plasma through an APACT 4004 platelet aggregation analyzer. Arachidonic acid [ADP] was used to gauge any alteration in platelet shape and aggregation process. The parent drugs showed some antiplatelets aggregation, however, their metal complexes demonstrated better efficacy

Spectroscopic and cytotoxic studies of losartan complexes

Use of drug-metal complexes for the treatment of several human diseases has resulted in significant progress in the field of medicinal inorganic chemistry. The current study describes the synthesis and characterization of Cu [II] and Ni [II] complexes of Losartan, an antihypertensive drug. These complexes were evaluated for their cytotoxic activity against four human cancer cell lines; SNB-19, HCT-15, COLO-205 and KB-3-1. Spectroscopic characterization revealed that during complex formation, the metal was bound through the nitrogen atoms of the tetrazole moiety of the losartan molecule. The molecular formulas of copper [[Cu [LS][2] Cl[2]].6H[2]O] and nickel [[Ni [LS][2]Cl[2]]. H[2]O] complexes were found to be in agreement with the analytical data obtained through elemental analysis. For both the complexes, metal to ligand ratios of 1:2 were calculated. As revealed by FTIR, UV-Visible, and 1H-NMR studies, both the complexes displayed octahedral geometries. Scanning electron microscopy [SEM] revealed marked changes in the morphology of the complexes, compared to the pure drug. From XRD studies, characteristic crystalline peaks of pure losartan were observed whereas no prominent peaks were observed for its complexes. Complexes were found to be inactive in the cytotoxic activity test performed using SNB-19, HCT-15, COLO-205 and KB-3-1 cell lines

Fluconazole and its interaction with metal [II] complexes: SEM, Spectroscopic and antifungal studies

The human digestive tract contains some 100 trillion cells and thousands of species of micro-organisms may be present as normal flora of this tract as well as other mucocutaneous junctions of the body. Candida specie is the most common organism residing in these areas and can easily invade the internal tissues in cases of loss of host defenses. Modifications of previously existing antifungal agents may provide new options to fight against these species. Inorganic compounds of different antifungals are under investigations. Present study report six complexes of fluconazole with Cu [II]], Fe[II], Cd[II], Co[II], Ni[II] and Mn[II] have been synthesized and characterized by elemental analysis, IR, UV and H-NMR. The elemental analysis and spectroscopic data were found in agreement with the expected values as the metal to ligand value was 1:2 ratios with two chlorides in coordination sphere. The morphology of each complex was studied using scanning electron microscope and compared with fluconazole molecule the flaky-slab rock like particles of pure fluconazole was also observed as reported earlier. However, the complexes of fluconazole were showed different morphology in their micrograph. Fluconazole and its complex derivatives have also been screened in vitro for their antifungal activity against Candida albican and Aspergillus niger by MIC method. The complexes showed varied activity ranging from 2-20%

Metal complexes of isonicotinylhydrazide and their antitubercular activity

The development and spreading of Multi Drug Resistant TB strains is hampering endeavours for the control and administration of tuberculosis [TB]. The expansion episodes of multi-medication safe strains of Mycobacterium tuberculosis against first and second line antituberculosis drugs on one side and the unfavourable effects of these drugs on the other side has led the enthusiasm of researcher towards the synthesis of metal complexes of various medication. This approach is born with the expectation of finding new antituberculous operators without or least reactions as well as being active against the resistant strains of Mycobacterium tuberculosis. This study concentrates on the screening of five metal complexes of isoniazid [INH] against five Mycobacterium tuberculosis strains. These strains have been confirmed by WHO being active and even proliferating safely even in the presence of pyrazinamide, isoniazid [INH], ethambutol and rifampicin. In this work INH was taken as reference medication. All synthesized complexes and INH were subjected for a month and a half in BACTEC MGIT 960 technique. INH and its Fe [II] complex restrained the development of all bacterial strains for merely two weeks, while the Fe[III], Cu[II], Co [II] and Mn [II] complexes repressed the development five strains for three weeks. Conclusively, the strains utilized in this study were discovered to be more susceptible to the later four complexes than the ligand [INH] drug and its Fe [II] complex. Furthermore, elemental analysis and atomic absorption of all complexes were conducted for the determination of metal to ligand ratio

Cytotoxic and acute toxicity studies of isoniazid derivatives

Cancer is ultimately the result of cells that hysterically grow and do not die. Cells can experience uncontrolled growth if there are mutations to DNA, and therefore, alterations to the genes involved in cell division. Cancer occurs when a cell's gene mutations make the cell unable to correct DNA damage and is unable to destroy itself. There are over 100 different types of cancer each classified by the type of initially affected cell. Isoniazid, a well-known antitubercular agent has been reported to exhibit some cytotoxic activity. This finding prompt us to carry out this study where isoniazid and its sixteen derivatives were studied for any possible cytotoxic activity against Human astrocytoma SNB-19 cells, human Dukes' type C colorectal adenocarcinoma HCT-15 cells, human Dukes' type D colorectal adenocarcinoma COLO-205 cells, and human prostate adenocarcinoma [grade IV] PC-3 cells. Among the test compounds, SN-07 [a phenacyl derivative with para phenyl substitution] demonstrated slight cytotoxic effects on two types of human colorectal adenocarcinoma cells HCT-15 and COLO-205. Moreover, the acute toxicity of the compounds was also estimated in which some compounds were evaluated with more LD[50] values than isoniazid

Newborn observation track and trigger [NOTT] chart

Use of early warning system scores and track-and-trigger charts is widespread in adult and paediatric hospitalized patients; but its use in neonatal group is not well recognized. The authors aimed to develop and implement neonatal observation track-and-trigger chart for use in babies on postnatal wards and to assess its efficacy in identifying neonates in need of urgent medical assessment and intervention. Core group developed Newborn Observation Track and Trigger [NOTT] chart for "At-Risk" and "At-High-Risk" Infants. A decision tree was devised based on 'low', 'medium' and 'high' scores. Sensitivity and specificity of NOTT chart's 'medium' and 'high' score was 96% and 90%, respectively. Positive and negative predictive value was 43% and 100%, respectively. NOTT chart is a valuable tool for assessment of neonates on postnatal wards. A prospective study, using large number of participants, would be beneficial to further corroborate this useful tool

Medium optimization for the production of amylase by Bacillus subtilis RM16 in Shake-flask fermentation

This study was carried out in shaking incubator and covers the optimization of culture conditions of Bacillus subtilis for the maximum production of amylase. Optimal activity was found to be 350 Uml[-1] when soluble starch was used as a substrate. Parameters taken into consideration to observe their effect on the optimum production of amylase include incubation time, incubation temperature, pH, inoculum size, carbon source, nitrogen source and metallic ions. All parameters were monitored in order to obtain high level of the enzyme units in cell-free broth. The established optimized conditions for Bacillus subtiliss train RM16 were found to be: incubation time 24 hours, temperature 40[degree]C and pH 8.0. Inoculum size was 5%, starch [1%] as a carbon source while yeast extract [1.5%] as a nitrogen source. Magnesium ions [0.1%] exerted maximum stimulating effect for the production of amylase which can be further used at large scale applications

Analyses of bile from gallbladders of fish [Arius platystomus, Arius tenuispinis, Pomadasys commersonni and Kishinoella tonggol]

Bile from gallbladders of Arius platystomus [Singhara], Arius tenuispinis [Khagga], Pomadasys commersonni [Holoola] and Kishinoella tonggol [Dawan] were derivatised and analysed by GC-MS for identification of bile acids and bile alcohols. Cholic acid and Chenodeoxycholic acid were found as major bile acids in Arius platystomus, Arius tenuispinis and Pomadasys commersonni. Other bile acids identified in Arius platystomus were allochenodeoxycholic acid, allodeoxycholic acid, 3 alpha,7 alpha,12 alpha -trihydroxy-24-methyl-5beta-cholestane-26-oic acid, and 3alpha,7alpha,12alpha, 24-tetrahydroxy-5alpha-cholestane-26-oic acid. Cholesterol was found as major bile alcohol in Arius platystomus, Arius tenuispinis and Pomadasys commersonni. Cholic acid was the major bile acid identified in the bile of Kishinoella tonggol while other bile acids included 3 alpha,7 alpha,12 alpha -tridydroxy-5alpha-cholestanoic acid and 3 alpha,7 alpha,12 alpha -tridydroxy-5beta-cholestanoic acid. Bile alcohol 5beta-cyprinol was present in significant amounts with 5beta-cholestane-3 alpha,7 alpha,12 alpha,24-tetrol being the other contributors in the bile of Kishinoella tonggol

Analgesic effects of crude extracts and fractions of Omani frankincense obtained from traditional medicinal plant Boswellia sacra on animal models

Objective: To investigate the analgesic effect of Boswellia sacra (B. sacra), which could support the Omani traditional uses of frankincense for muscle, stomach, and arthritis pain. Methods: The crude extract, the essential oils and various sub-fractions of the crude methanol extract (each 300 mg/kg of the body weight of the animal) obtained from the resin of B. sacra were administered orally, and were evaluated for their analgesic activities by using two well known models of pain in mice, viz. acetic acid induced writhing test and formalin induced pain test in mice. Results: Of 13 samples, almost all of them were effective at an orally administered dose of 300 mg/kg of the body weight. The acetic acid induced writhes were inhibited in all the three phases with comparable values to the standard drug aspirin (300 mg/kg of body weight) with inhibition of 67.6% in phase I, 66.8% in phase II, and 37.9% in phase III. At the same time, all the tested samples were found effective in both the early and the late phases of formalin test. In formalin test, most of the tested samples showed more inhibitory effects as compared to the standard drug aspirin (300 mg/kg of body weight), which showed 36.2% and 29.6% inhibition in early and late phases respectively. Among the tested samples, the most significant inhibition was produced by Shabi frankincense oil (57.5% in early phase, and 55.6% in late phase). Interestingly, the extracts showed comparable percentage of inhibition to the oil and found in the following order: 60% chloroform. /n-hexane sub-fraction (55.3% in early phase, and 66.7% in late phase), and 70% chloroform. /n-hexane sub-fraction (59.6% in early phase, and 63.0% in late phase). Conclusions: The present study provided the scientific justification about the analgesic properties of the essential oils, extract, and various sub-fractions obtained from the resin of B. sacra, thus validating its use in traditional folk medicines and other products; and hence supporting the development in the analgesic properties of bioactive natural substances.

In vitro/in vivo effect of Citrus limon [L. Burm. f.] juice on blood parameters, coagulation and anticoagulation factors in rabbits

The genus Citrus of the family Rutaceae includes many species e.g. Citrus indica, Citrus aurantifolia and Citrus limon, among which Citrus limon L. Burm. f. has been reported to have highest antimicrobial activity. It is used as antidote against certain venom, due to its platelet inhibitory effect and also reported to have hypocholesterolemic effect. However its anticoagulant and thrombolytic effect were not been investigated, hence a prospective in-vitro/in-vivo study was designed to determine the effect of Citrus limon on blood parameters, coagulation and anticoagulation factors. Invitro tests revealed highly significant increase in thrombin time and activated partial thromboplastin time by Citrus limon, whereas fibrinogen concentration was significantly reduced in comparison to control, however prothrombin time was not affected significantly. In-vivo testing of Citrus limon was done at three different doses i.e. 0.2ml/kg, 0.4ml/kg and 0.6ml/kg in healthy rabbits. Significant changes were observed in hematological parameters such as erythrocytes, hemoglobin and mean corpuscular hemoglobin concentration. Bleeding time and thrombin time was significantly prolonged and there was increase in protein C and thrombin antithrombin complex levels. These results may be due to inactivation of thrombin because it significantly decreases fibrinogen concentration and inhibit platelet aggregation. Citrus limon showed maximal anticoagulant effect at 0.4ml/kg, which suggest that Citrus limon possesses an antithrombin component and could prevent thrombosis playing a cardio protective role

Annona squamosa Linn: Cytotoxic activity found in leaf extract against human tumor cell lines

Cancer is a common cause of death in human populations. Surgery, chemotherapy and radiotherapy still remain the corner stone of treatment. However, herbal medicines are gaining popularity on account of their lesser harmful side effects on non-targeted human cells and biological environment. Annona squamosa Linn is a common delicious edible fruit and its leaf have been used for the treatment in various types of diseases

The objective of present study is to determine the anticancer potential of the organic and aqueous extracts of leaf of Annona squamosa L. MTT [3-[4, 5-dimethylthiazole-2yl]-2, 5-biphenyl tetrazolium bromide] assay against hepatocellular carcinoma cell line BEL-7404, lung cancer line H460, human epidermoid carcinoma cell line KB-3-1, prostatic cancer cell line DU145, breast carcinoma cell line MDA-MB-435, and colon cancer cell line HCT-116 Human primary embryonic kidney cell line HEK293 as control were used for the study

The crude extract [Zed] and Ethyl acetate extract [ZE] were found significant anticancer activity only on human epidermoid carcinoma cell line KB-3-1 and colon cancer cell line HCT-116

Analgesic effects of crude extracts and fractions of Omani frankincense obtained from traditional medicinal plant Boswellia sacra on animal models

OBJECTIVE@#To investigate the analgesic effect of Boswellia sacra (B. sacra), which could support the Omani traditional uses of frankincense for muscle, stomach, and arthritis pain.@*METHODS@#The crude extract, the essential oils and various sub-fractions of the crude methanol extract (each 300 mg/kg of the body weight of the animal) obtained from the resin of B. sacra were administered orally, and were evaluated for their analgesic activities by using two well known models of pain in mice, viz. acetic acid induced writhing test and formalin induced pain test in mice.@*RESULTS@#Of 13 samples, almost all of them were effective at an orally administered dose of 300 mg/kg of the body weight. The acetic acid induced writhes were inhibited in all the three phases with comparable values to the standard drug aspirin (300 mg/kg of body weight) with inhibition of 67.6% in phase I, 66.8% in phase II, and 37.9% in phase III. At the same time, all the tested samples were found effective in both the early and the late phases of formalin test. In formalin test, most of the tested samples showed more inhibitory effects as compared to the standard drug aspirin (300 mg/kg of body weight), which showed 36.2% and 29.6% inhibition in early and late phases respectively. Among the tested samples, the most significant inhibition was produced by Shabi frankincense oil (57.5% in early phase, and 55.6% in late phase). Interestingly, the extracts showed comparable percentage of inhibition to the oil and found in the following order: 60% chloroform/n-hexane sub-fraction (55.3% in early phase, and 66.7% in late phase), and 70% chloroform/n-hexane sub-fraction (59.6% in early phase, and 63.0% in late phase).@*CONCLUSIONS@#The present study provided the scientific justification about the analgesic properties of the essential oils, extract, and various sub-fractions obtained from the resin of B. sacra, thus validating its use in traditional folk medicines and other products; and hence supporting the development in the analgesic properties of bioactive natural substances.

Antineoplastic activity of Holoptelea integrifolia [Roxb.] Planch bark extracts [in vitro]

Cancer remains the major public health concern with a number of cancer patients relying on chemotherapy as a treatment option. Although, advances in biomedical research have led to increased anticancer agents in recent years, the treatment is not always effective due to resistance, toxicity or other factors. Phytochemicals and their active components isolated from plants have provided diversified effective drugs many of them are currently used against cancer and other diseases. Holoptelea integrifolia [Roxb] Planch [Ulmaceae] is a widely distributed plant in many parts of the world, also grown in gardens of Pakistan. It is an ornamental plant with certain medicinal characteristics due to many valuable and active phyto constituents in various parts of the plant. We looked at in vitro antineoplastic effects of four different extracts, in butanol [BMBU], hexane [BMHx], ethyl acetate [BMET] and chloroform [BMCHF], from bark of Holoptelea integrifolia on small cell lung cancer, breast, prostate, coloretal and hepatocellular cancer cell lines. Plant extracts BMHx and BMET showed significant cytotoxic effects on breast and prostate cancer cells. These preliminary studies are encouraging to proceed further this research in future, regarding the isolation of active phytoconstituents in these extracts as well as its mechanism in chemoprevention and combination anticancer therapy

Use of enteral nutritional supplementationþ:þ a survey of level II and III neonatal units in England

Enteral nutritional supplementation is widely used in preterm babies on Neonatal Units [NNUs]. There is little published evidence on appraising their long-term efficacy. We evaluated the current practice of enteral nutritional supplementation in 96 level II and III NNUs in England. 96%, 98%, 98% and 56% units use breast milk fortification [BMF], iron, multivitamins and folic acid supplementation respectively. Iron, multivitamins and folic acid supplements are routinely commenced in babies < 35 weeks gestation by 73%, 68% and 39% NNUs respectively. Seventy eight percent NNUs only use BMF for babies that are not gaining weight. Continuing variable practice of enteral nutritional supplementation and current use of anecdotal evidence and best guess recommendations highlights the need for a unified approach and collaborative multinational research to produce standardised guidelines

Use of polyethylene glycol in children less than 3 years of age

Chronic constipation is extremely common gastrointestinal problem in children. Polyethylene glycol [PEG] has been shown to be effective for both disimpaction and maintenance treatment in older children with chronic constipation. Literature review was carried out using Medline via PubMed [1950 to 2010], Cinahl [1982 - 2010] and Embase [1974 to 2010] to evaluate the efficacy and safety of PEG in infants and children less than 3 years of age. There were no relevant reviews in the Cochrane Library. Only 5 relevant studies were found for children in the age group below 3 years. Pooled analysis of all the studies showed a statistically significant difference in the stool frequency before and after treatment with polyethylene glycol [p < 0.001]. Although, limited published evidence to date supports its use in terms of safety and efficacy, larger randomized controlled trials are needed especially in young infants to substantiate the evidence

Retention of knowledge of the paediatric life support guidelines

Paediatric Life Support [PLS] courses are thought to significantly increase knowledge of paediatric resuscitation for all professional groups. PLS and Newborn Life Support [NLS] guidelines were revised and updated in 2005. In a telephonic survey, the retention and awareness of the changes in PLS guidelines were evaluated among 100 junior paediatric doctors. Overall, second on-call doctors tended to score higher than the first on-call doctors [score 6.55 +/- 2.25 vs. 5.89 +/- 2.17 respectively, p = 0.062]. Doctors who attended PLS courses after 2005 tended to have higher scores. There is a need to streamline formalised regular updates [e.g. annual online written multiple choice questions] and in-house rehearsals using mock emergency scenarios at local, regional and national level

Diabetes and oral health: a case-control study

Diabetes mellitus, according to World Health Organization [WHO] is a silent epidemic which affects large number of people around the world and is directly related to the oral health status of the patients. To know the prevalence of common dental diseases such as dental caries, periodontal diseases [pyorrhea], and treatment needs in a group of adult diabetic patients in private medical establishments of Tumkur city, south India, in comparison with non-diabetic patients. To create awareness among general medical practitioners about the common oral manifestations of diabetes and the importance of periodical dental check up for diabetics. A group of 300 diabetic patients [males = 186, females = 114] and a control group of 300 non-diabetics [males = 180, females = 120] matched by age and sex were examined according to WHO criteria, for a period of eight months. The prevalence of dental caries was comparatively more in non-diabetics [32.3%] than in diabetics [13.6%]. However, the prevalence of periodontal diseases [pyorrhea] was more in diabetics [92.6%] when compared to non-diabetics [83%]. Oral health is an integral part of general health. Though dental caries was comparatively low in diabetics, periodontal status was compromised. Complex treatment needs was more in the diabetics [58%] when compared to controls [41%]. Regular follow-up of dental problems of the diabetics and oral health education is much required

Cardiac arrhythmias and left ventricular hypertrophy in systemic hypertension

Hypertensive left ventricular hypertrophy [LVH] is associated with increased risk of arrhythmias and mortality. Objective was to investigate the prevalence of cardiac arrhythmias and LVH in systemic hypertension. In all subjects blood pressure was measured, electrocardiography and echocardiography was done. Holter monitoring and exercise test perform in certain cases. There were 500 hypertensive patients, 156 [31.2%] men and 344 [69%] women >30 years of age in the study. Among them 177 [35.4%] were diabetic, 224 [45%] were dyslipidemia, 188 [37.6%] were smokers, and 14 [3%] had homocysteinemia. Duration of hypertension [HTN] was >/= 2 years]. Mean systolic BP [SBP] was 180 +/- 20 mm Hg and diastolic BP [DBP] was 95 +/- 12 in male and female patients. Left ventricular mass index [LVMI] was 119.2 +/- 30 gm/m2 in male while 103 +/- 22 gm/m2 in female patients. Palpitation was seen in 126 [25%] male and 299 [59.8%] female patients. Atrial fibrillation was noted in 108 [21.6%] male and 125 [25%] female patients, 30 [6%] male and 82 [16.4%] female patients had atrial flutter. Ventricular tachycardia was noted in 37 [7.4%] male and 59 [11.8%] female patients. Holter monitoring showed significant premature ventricular contractions [PVC'S] in 109 [21.8%] male and 128 [25.69%] female patients while Holter showed atrial arrhythmias [APC'S] in 89 [17.8%] males and 119 [23.8%] females. Angiography findings diagnosed coronary artery disease in 119 [23.8%] with CAD male and 225 [45%] without CAD while 47 [9.4%] females presented with CAD and 109 [21.8%] without CAD. A significant association has been demonstrated between hypertension and arrhythmias. Diastolic dysfunction of the left ventricle, left atrial size and function, as well as LVH have been suggested as the underlying risk factors for supraventricular, ventricular arrhythmias and sudden death in hypertensives with LVH