Phytochemicals and bioactive compounds effective against acute myeloid leukemia: A systematic review.

This systematic review identified various bioactive compounds which have the potential to serve as novel drugs or leads against acute myeloid leukemia. Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy that arises from the dysregulation of cell differentiation, proliferation, and cell death. The risk factors associated with the onset of AML include long-term exposure to radiation and chemicals such as benzene, smoking, genetic disorders, blood disorders, advancement in age, and others. Although novel strategies to manage AML, including a refinement of the conventional chemotherapy regimens, hypomethylating agents, and molecular targeted drugs, have been developed in recent years, resistance and relapse remain the main clinical problems. In this study, three databases, PubMed/MEDLINE, ScienceDirect, and Google Scholar, were systematically searched to identify various bioactive compounds with antileukemic properties. A total of 518 articles were identified, out of which 59 were viewed as eligible for the current report. From the data extracted, over 60 bioactive compounds were identified and divided into five major groups: flavonoids, alkaloids, organosulfur compounds, terpenes, and terpenoids, and other known and emerging bioactive compounds. The mechanism of actions of the analyzed individual bioactive molecules differs remarkably and includes disrupting chromatin structure, upregulating the synthesis of certain DNA repair proteins, inducing cell cycle arrest and apoptosis, and inhibiting/regulating Hsp90 activities, DNA methyltransferase 1, and histone deacetylase 1.

Toxicity of Nanoparticles in Biomedical Application: Nanotoxicology.

Nanoparticles are of great importance in development and research because of their application in industries and biomedicine. The development of nanoparticles requires proper knowledge of their fabrication, interaction, release, distribution, target, compatibility, and functions. This review presents a comprehensive update on nanoparticles' toxic effects, the factors underlying their toxicity, and the mechanisms by which toxicity is induced. Recent studies have found that nanoparticles may cause serious health effects when exposed to the body through ingestion, inhalation, and skin contact without caution. The extent to which toxicity is induced depends on some properties, including the nature and size of the nanoparticle, the surface area, shape, aspect ratio, surface coating, crystallinity, dissolution, and agglomeration. In all, the general mechanisms by which it causes toxicity lie on its capability to initiate the formation of reactive species, cytotoxicity, genotoxicity, and neurotoxicity, among others.

Construction of Femoral Vessel Nomograms for Planning Cardiac Interventional Procedures in Children 0-4 Years Old.

The objectives of this study were to construct femoral artery (FA) and femoral vein (FV) nomograms in children aged 0-4 years and to construct probability curves for the occurrence of arterial access complications based on the size of the FA. The FV and FA are commonly accessed during cardiac catheterizations in children with congenital heart diseases (CHD). However, nomograms for vessel dimensions based on child's age or size are not available. This knowledge may be helpful for interventional planning. A prospective study was performed on 400 children (age 0-4 years) with CHD undergoing cardiac catheterizations over a 3-year period. Ultrasound evaluation of the right and left FA and FV was performed under anesthesia prior to vascular access. Regression modeling was applied to derive nomograms based on quantile polynomial regression, which yielded good fit to the data judged by R-squared. GAMLSS transformation method was used to formulate smoothed percentiles. A separate prospective evaluation of FA to determine the size below which loss of pulse (LOP) are likely to occur was performed. Nomograms for FA and FV diameter and cross-sectional area against age and body surface area and probability curves for FA LOP were constructed. It is now possible to examine ultrasound-based normal sizes of femoral vein and artery in children 0-4 years of age. Femoral vessel nomograms and LOP probability curves may help with interventional planning. Future studies with larger sample size, including children of other ages may be useful.

HPTLC Method for Estimation of Topiramate in Solubility Studies, Diffusion Studies, Plasma, Brain Homogenate and Pharmaceutical Formulation.

Topiramate, 2,3:4,5-bis-O-(1-methylethylidene)-ß-d-fructopyranose, is an anticonvulsant drug indicated in the treatment and control of partial seizures and severe tonic-clonic (grand mal) seizures in adults and children. An economic and rapid high-performance thin-layer chromatographic (HPTLC) method was developed and was validated for the quantitative determination of topiramate in plasma, brain homogenate and pharmaceutical formulation. The simple extraction method was used for the isolation of topiramate from formulation, plasma and brain homogenate samples. HPTLC separation was achieved on an aluminum-backed layer of silica gel 60F254 plates using toluene : acetone (5.0 : 2.0, v/v) as mobile phase. Spots of developed plates were visualized by spraying of reagent [3.0% phenol in the mixture of ethanol : sulfuric acid (95 : 5, v/v)]. Quantitation was achieved by densitometric analysis at 340 nm over the concentration range of 1,000-5,000 ng/spot. The method was found to give compact spot for the drug (Rf: 0.61 ± 0.018). The regression analysis data for the calibration plots showed good relationship with a correlation coefficient of 0.9983. The minimum detectable amount was found to be 165 ng/spot, whereas the limit of quantitation was found to be 500 ng/spot. Statistical analysis of the data showed that the method is precise, accurate, reproducible and selective for the analysis of topiramate. The developed method was successfully employed for the estimation of topiramate in samples of equilibrium solubility study, diffusion study, microemulsion formulation and suspension formulation (developed in-house), rat plasma and rat brain homogenate samples.

Sensitive and robust methods for simultaneous determination of beclomethasone dipropionate and formoterol fumarate dihydrate in rotacaps.

Fixed dose combination containing beclomethasone dipropionate (BDP) and formoterol fumarate dihydrate (FFD) is used in the treatment of asthma in form of dry powder inhaler. Two methods are described for the simultaneous determination of BDP and FFD in commercial rotacap formulation. The first method was based on HPTLC separation of the two drugs followed by densitometric measurements of their spots at 220 nm. The separation was carried out on Merck HPTLC aluminum sheets precoated with silica gel 60F254 using hexane:ethyl acetate:methanol:formic acid (2.0:2.5:2.0:0.2, v/v/v/v) as mobile phase. The linearity was found to be in the range of 2.4-8.4 µg/spot and 80-280 ng/spot for BDP and FFD, respectively. The second method was based on HPLC separation of the two drugs on the reversed phase Enable HPLC Analytical C18 G 120Å (250 × 4.6 mm, 5 µm) column at ambient temperature using a mobile phase consisting of methanol:acetonitrile:phosphate buffer adjusted to pH 3.6 using orthophosphoric acid (65:25:10, v/v/v). Quantitation was achieved with UV detection at 220 nm based on peak area with linear calibration curves at concentration ranges of 10-200 and 0.3-6.0 µg/mL for BDP and FFD, respectively. Both methods were validated in terms of precision, robustness, recovery and limits of detection and quantitation. The robustness of both methods was assessed using experimental design and results were analyzed by statistical and graphical approaches. Rotacaps formulation containing BDP (200/400 µg) and FFD (6 µg) were successfully quantified using the proposed methods. The proposed methods can be used as sensitive, precise, accurate and robust methods for quantification of BDP and FFD in Rotacaps.

Hydrochloride salt co-crystals: preparation, characterization and physicochemical studies.

Co-crystallization approach for modification of physicochemical properties of hydrochloride salt is presented. The objective of this investigation was to study the effect of co-crystallization with different co-crystal formers on physicochemical properties of fluoxetine hydrochloride (FH). FH was screened for co-crystallization with a series of carboxylic acid co-formers by slow evaporation method. Photomicrographs and melting points of crystalline phases were determined. The co-crystals were characterized by FTIR, DSC and PXRD methods. Solubility of co-crystals was determined in water and buffer solutions. Powder and intrinsic dissolution profiles were assessed for co-crystals. Physical mixtures of drug and co-formers were used for comparisons at characterizations and physicochemical properties evaluation stages. Four co-crystals of FH viz. Fluoxetine hydrochloride-maleic acid (FH-MA), Fluoxetine hydrochloride-glutaric acid (FH-GA), Fluoxetine hydrochloride-L-tartaric acid (FH-LTA) and Fluoxetine hydrochloride-DL-tartaric acid (FH-DLTA) were obtained from screening experiments. Physical characterization showed that they have unique crystal morphology, thermal, spectroscopic and X-ray diffraction properties. Solubility and dissolution studies showed that Fluoxetine hydrochloride-maleic acid co-crystal possess high aqueous solubility in distilled water, pH 4.6, 7.0 buffer solutions and dissolution rate in distilled water than that of pure drug. Co-crystal formation approach can be used for ionic API to tailor its physical properties.

Determinants of rapid progression to immunodeficiency syndrome among people infected with Human Immunodeficiency Virus, Kerala, India.

CONTEXT: Human Immunodeficiency Virus (HIV) infection progresses in almost all infected persons to Acquired Immunodeficiency Syndrome (AIDS). The aim of the study was to find out the determinants of rapid progression of immunodeficiency among people infected with HIV in Thiruvananthapuram district of Kerala, India. SETTINGS AND DESIGN: The study design used was case control. The setting of the study was antiretroviral treatment (ART) centre of Government Medical College and the self-help group of HIV patients located at Thiruvananthapuram, Kerala. MATERIALS AND METHODS: Cases were people having any one or more of the AIDS defining clinical conditions within 3 years from the diagnosis of HIV infection. Controls were people diagnosed as having HIV at least 3 years ago and with no AIDS-defining clinical conditions till the date of the study. Sample size was 149 with a control case ratio of 1.5:1. STATISTICAL ANALYSIS USED: Mean (standard deviation) and proportions were used to describe the data. Chi-square test and t test were done to test the hypotheses. Binary logistic technique was used to find out the predictors of the outcome. RESULTS: A regression (Binary Logistic) model was used to predict the progression. Fungal infection of nail [adjusted Odds Ratio (OR), 6.4 (1.4, 28.9)] and oral candidiasis [adjusted OR, 2.6 (1.1, 6.4)] were the clinical conditions significantly associated with rapid progression. The significant social factors included non-exposure to professional counseling [adjusted OR, 7.1 (2.0, 24.5)] and the feeling of being stigmatized - felt as preoccupation with thoughts that they are gossiped about and the increase in visitors to "check them out" [adjusted OR, 26.1 (4.9, 138.4)]. The protective nutritional factors in the model were frequent consumption of legumes [adjusted OR, 0.12 (0.04, 0.36)], eggs [adjusted OR, 0.29 (0.09, 0.93)], and plenty of oral fluids [adjusted OR, 0.18 (0.07, 0.47)]. CONCLUSIONS: An approach incorporating the clinical, social, and nutritional factors may retard the progression of HIV infection.

Ecology and abundance of zooplankton in Karanja reservoir.

The present work aims to study the Zooplankton seasonal distribution and diversity in Karanja reservoir, Bidar district for the period of two years from October 2001 to September 2003. We have recorded 36 species of which, 15 species belongs to rotifera, 11 species belongs to cladocera, nine species belongs to copepoda and ostracoda three species. Among zooplankton, particularly rotifera was the dominant group throughout the study period and highest count was recorded in the month of March 2003. Cluster analysis was also revealed by dendrogram and Shannon diversity index is also presented. Zooplankton community is also correlated with physicochemical parameters.

Concentration of heavy metals in Karanja reservoir, Bidar district, Karnataka, India.

In this study, some heavy metals concentrations (Zn, Pb, Fe, Mn, Cu, Ni) and other physico-chemical parameters were studied during October 2001 to September 2003 in Karanja reservoir, Bidar district. Water quality parameters were collected monthly basis whereas heavy metals were analyzed by Atomic Adsorption Spectrometer (AAS). Heavy metals have shown within the permissible limits, except Fe and Ni were recorded higher values in southwest monsoon, where as Mn has showed higher concentration in northeast monsoon in and summer. All other physico-chemical parameters are with in the permissible limit. Water is moderately hard and reservoir is productive.

Chemistry of groundwater in Gulbarga district, Karnataka, India.

Groundwater quality of Gulbarga District is extensively monitored for two years of study period from October 1999 to September 2001. Twenty-five different sampling stations were selected for the study purpose in the city and five selected villages in the district. Gulbarga districts lies in the northern plains of Karnataka State, covers an area of 16,244 km2 and lies between 16 degrees-11' and 17 degrees-19'N latitude and 76 degrees-54'E longitude The study revealed that the water sources in the area are heavily polluted. The major water quality parameters exceeding the permissible limits during all the seasons are total hardness, calcium hardness, magnesium hardness, alkalinity and MPN (Bacterial count) and other parameters have shown distinctive variation in different stations and season. Most of these parameters are correlated with one another. Statistical analysis of the data is presented.

A study of CSF catecholamine and its metabolites in acute and convalescent period of encephalitis.

AIMS: To evaluate cerebrospinal fluid (CSF) catecholamine (CA) and its metabolites in encephalitis patients in acute and convalescent period and correlate these with clinical and magnetic resonance imaging (MRI) features. SUBJECTS AND METHODS: Patients with acute encephalitis diagnosed on the basis of clinical, CSF, MRI and virological parameters underwent detailed neurological evaluation including Glasgow Coma Scale (GCS), Unified Parkinson's Disease Rating Scale (UPDRS) and Dystonia Rating Scale. Cranial MRI was carried out and CSF dopamine (DA), norepinephrine (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxytryptamine (5HT) levels were estimated by High Performance Liquid Chromatography (HPLC). The CSF catecholamine levels were compared with convalescent phase as well as with controls. These levels were also correlated with parkinsonian features, dystonia and radiological abnormalities. RESULTS: There were 29 encephalitis patients; whose age ranged between 2 and 65 years, 4 were females and 11 children. 25 patients had Japanese encephalitis (JE) and 4 nonspecific encephalitis. The mean GCS score was 8 and 13 had seizures. Movement disorders were present in 13 patients and included parkinsonian features in 5, dystonia in 1 and combination of both in 7 patients. MRI revealed abnormalities in 15 out of 21 patients and included thalamic lesion in 10, globus pallidus in 4, putamen in 5, caudate in 4 and midbrain in 9 patients. In acute stage NE, DOPAC, 5HT and HVA levels were significantly lower compared to controls. NE levels significantly correlated with dystonia and thalamic lesions. Convalescent CSF study revealed significantly lower levels of DOPAC compared to acute phase. CSF catecholamine levels in encephalitis patients with and without movement disorders were not significantly different. CONCLUSION: In encephalitis, catecholamine and its metabolites are lower in acute and convalescent phase. Norepinephrine level correlates with dystonia and thalamic lesions.

Psoriasis: current concepts and new approaches to therapy.

Psoriasis is a common disorder characterized by marked increases in keratinocyte proliferation, abnormal patterns of keratinocyte differentiation, prominent alterations in dermal capillary vasculature and the presence of dermal and epidermal T cells, monocytes/macrophages and neutrophils. It is now known that psoriasis can occur due to abnormalities in essential fatty acid metabolism, lymphokine secretion, free radical generation, lipid peroxidation and eicosanoid metabolism. It is possible to suppress almost completely psoriatic lesions by judicious use of methotrexate, cyclosporine A, and eicosapentaenoic acid. Our studies have shown that in patients with psoriasis there is an increase in the generation of free radicals with an alteration in essential fatty acid metabolism and that side-effects of anti-cancer drugs can be blocked by essential fatty acids in vivo. Thus, essential fatty acid metabolism seems to play a crucial role both in the pathogenesis and treatment of psoriasis.