Global burden of injuries attributable to alcohol consumption in 2004: a novel way of calculating the burden of injuries attributable to alcohol consumption

Background

Alcohol consumption is a major risk factor for injuries; however, international data on this burden are limited. This article presents new methods to quantify the burden of injuries attributable to alcohol consumption and quantifies the number of deaths, potential years of life lost (PYLL), and disability-adjusted life years (DALYs) lost from injuries attributable to alcohol consumption for 2004.

Methods

Data on drinking indicators were obtained from the Comparative Risk Assessment study. Data on mortality, PYLL, and DALYs for injuries were obtained from the World Health Organization. Alcohol-attributable fractions were calculated based on a new risk modeling methodology, which accounts for average and heavy drinking occasions. 95% confidence intervals (CIs) were calculated using a Monte Carlo simulation method.

Results

In 2004, 851,900 (95% CI: 419,400 to 1,282,500) deaths, 19,051,000 (95% CI: 9,767,000 to 28,243,000) PYLL, and 21,688,000 (95% CI: 11,097,000 to 32,385,000) DALYs for people 15?years and older were due to injuries attributable to alcohol consumption. With respect to the total number of deaths, harms to others were responsible for 15.1% of alcohol-attributable injury deaths, 14.5% of alcohol-attributable injury PYLL, and 11.35% of alcohol-attributable injury DALYs. The overall burden of injuries attributable to alcohol consumption corresponds to 17.3% of all injury deaths, 16.7% of all PYLL, and 13.6% of all DALYs caused by injuries, or 1.4% of all deaths, 2.0% of all PYLL, and 1.4% of all DALYs in 2004.

Conclusions

The novel methodology described in this article to calculate the burden of injuries attributable to alcohol consumption improves on previous methodology by more accurately calculating the burden of injuries attributable to one??s own drinking, and for the first time, calculates the burden of injuries attributable to the alcohol consumption of others. The burden of injuries attributable to alcohol consumption is large and is entirely avoidable, and policies and strategies to reduce it are recommended.     

Identification of 5-(3-(methylsulfonyl)phenyl)-3-(4-(methylsulfonyl)phenyl)-3H-imidazo[4,5-b]pyridine as novel orally bioavailable and metabolically stable antimalarial compound for further exploration

Malaria continues to be a significant public health problem threatened by the emergence and spread of resistance to artemisinin-based combination therapies and marked half a million deaths in 2016. A new imidazopyridine chemotype has been envisaged through scaffold-hopping approach combined with docking studies for putative-binding interactions with Plasmodium falciparum phosphatidylinositol-4-kinase (PfPI4K) target. The docking results steered to the synthesis of compound 1 [5-(3-(methylsulfonyl)phenyl)-3-(4-(methylsulfonyl)phenyl)-3H-imidazo[4,5-b]pyridine] followed by the in vitro screening for antiplasmodial activity and ADME-PK studies. Combined with potent antimalarial activity of compound 1 (Pf3D7 IC₅₀ = 29 nM) with meager in vitro intrinsic clearance, moderate plasma-protein binding, and acceptable permeability, compound 1 displayed sustained exposure and high oral bioavailability in mice and can thus have the potential as next generation PI4K inhibitor for in vivo studies.     

Parkia javanica Extract Induces Apoptosis in S-180 Cells via the Intrinsic Pathway of Apoptosis

Parkia javanica is a leguminous tree, various parts of which are used as food and folklore medicine by the ethnic groups of northeastern India. The present study investigates the in vitro and in vivo anticancer effect of aqueous methanol extract of P. javanica fruit (PJE). HPLC analysis was done to establish the fingerprint chromatogram of PJE and its in vitro radical scavenging activity was measured. PJE caused significant cytotoxicity in sarcoma-180 (S-180), A549, AGS, and MDA-MB435S cancer cells in vitro. Exploration of the mechanistic details in S-180 cells suggested that the reduced cell viability was mediated by induction of apoptosis. Increased expression of proapoptotic proteins such as p53, p21, Bax/Bcl2, cytochrome c (Cyt c), caspase 9, and cleaved poly(ADP-ribose) polymerase, and decrease in proliferative and antiapoptotic markers (Ki-67, Proliferating Cell Nuclear Antigen [PCNA], Bcl-2) validated the anticancer effect of PJE. A decline in the relative fluorescence emission upon staining S-180 cells with Rhodamine 123 (Rh 123), enhanced expression of cytosolic Cyt c and mitochondrial Bax, and inhibition of apoptosis in the presence of caspase-9 inhibitor in PJE-treated cells indicated intrinsic pathway of apoptosis. Liver function test and hepatic antioxidant enzymes demonstrated non-toxicity of PJE. Finally, the detection of PJE in sera by HPLC confirmed its bioavailability.     

Improvement in Dissolution Rate of Cefuroxime Axetil by using Poloxamer 188 and Neusilin US2

A combination of fusion and surface adsorption techniques was used to enhance the dissolution rate of cefuroxime axetil. Solid dispersions of cefuroxime axetil were prepared by two methods, namely fusion method using poloxamer 188 alone and combination of poloxamer 188 and Neusilin US2 by fusion and surface adsorption method. Solid dispersions were evaluated for solubility, phase solubility, flowability, compressibility, Kawakita analysis, Fourier transform-infrared spectra, differential scanning calorimetry, powder X-ray diffraction study, in vitro drug release, and stability study. Solubility studies showed 12- and 14-fold increase in solubility for solid dispersions by fusion method, and fusion and surface adsorption method, respectively. Phase solubility studies showed negative ΔG⁰_tr values for poloxamer 188 at various concentrations (0, 0.25, 0.5, 0.75 and 1%) indicating spontaneous nature of solubilisation. Fourier transform-infrared spectra and differential scanning calorimetry spectra showed that drug and excipients are compatible with each other. Powder X-ray diffraction study studies indicated that presence of Neusilin US2 is less likely to promote the reversion of the amorphous cefuroxime axetil to crystalline state. in vitro dissolution studies, T50% and mean dissolution time have shown better dissolution rate for solid dispersions by fusion and surface adsorption method. Cefuroxime axetil release at 15 min (Q15) and DE15 exhibited 23- and 20-fold improvement in dissolution rate. The optimized solid dispersion formulation was stable for 6 months of stability study as per ICH guidelines. The stability was ascertained from drug content, in vitro dissolution, Fourier transform-infrared spectra and differential scanning calorimetry study. Hence, this combined approach of fusion and surface adsorption can be used successfully to improve the dissolution rate of poorly soluble biopharmaceutical classification system class II drug cefuroxime axetil.     

Efficacy of oral miltefosine in visceral leishmaniasis in rural West Bengal, India

Context:

Visceral leishmaniasis (VL), also known as Kala-azar (KA) is a public health problem of tropical and subtropical countries, which infects about 12 million people annually, out of which about 1.5 million are new cases. India contributes a major share of the global burden of VL. For many years leishmaniasis has been treated with pentavalent antimonials. Antimony resistance is a problem in India and in other different geographic areas of the world. Amphotericin B deoxycholate and pentamidine isethionate are effective by parenteral administration and associated with toxicities. The quest for an effective, orally administered, non-toxic and less expensive alternative resulted in the identification of miltefosine (hexadecylphosphocholine). In India, therapeutic efficacy of miltefosine in VL was assessed by many groups of scientists, mainly from Bihar and Uttar Pradesh. No such data is available from West Bengal.

Aims:

The present study was designed to observe the efficacy of miltefosine in VL in rural West Bengal.

Materials and Methods:

A total of 71 parasitologically proven VL patients participated in the study who received miltefosine in accordance with the National Vector Born Disease Control Programme (NVBDCP) of India and were followed up for the following one year.

Results:

The overall efficacy of the drug was 93% and no significant adverse side effects were observed during the study period.

Conclusions:

The study concludes that miltefosine is effective, well tolerated, and easily administrable drug in the treatment of visceral leishmaniasis at the field levels.KEY WORDS: India, visceral leishmaniasis, miltefosine     

Changes in agglomeration of fullerenes during ingestion and excretion in Thamnocephalus platyurus

The crustacean Thamnocephalus platyurus was exposed to aqueous suspensions of fullerenes C(60) and C(70) . Aqueous fullerene suspensions were formed by stirring C(60) and C(70) as received from a commercial vendor in deionized water (termed aqu/C(60) and aqu/C(70) ) for approximately 100 d. The Z-average (mean hydrodynamic) diameters of aqu/C(60) and aqu/C(70) aggregates as measured by dynamic light scattering were 517?±?21?nm and 656?±?39?nm (mean?±?95% confidence limit), respectively. Exposure of T. platyurus to fullerene suspensions resulted in the formation of dark masses in the digestive track visible under a stereo microscope (×40 magnification). Fullerene ingestion over 1?h of exposure was quantitatively determined after extraction and analysis by high-performance liquid chromatography-mass spectrometry (HPLC-MS). One-hour exposures (at 3?mg/L and 6?mg/L) resulted in aqu/C(60) burdens of 2.7?±?0.4?μg/mg and 6.8?±?1.5?μg/mg wet weight, respectively. Thin-section transmission electron microscopy (TEM) images of aqu/C(60) -exposed T. platyurus showed the formation in the gut of fullerene agglomerates (5-10?μm) that were an order of magnitude larger than the suspended fullerene agglomerates. Upon excretion, the observed fullerene agglomerates were in the 10- to 70-μm size range and settled to the bottom of the incubation wells. In contrast to the control polystyrene microspheres, which dispersed after depuration, the aqu/C(60) agglomerates (greater than two orders of magnitude larger than the suspended fullerenes) remained agglomerated for up to six months. When exposed to fullerenes, T. platyurus shows the potential to influence agglomerate size and may facilitate movement of these nanoparticles from the water column into sediment.     

Genotoxic effects after in vivo exposure of vegetable extracts containing heavy metals from the Dhapa area of Calcutta, India. I. Effects of cauliflower, spinach and radish.

Several reports have indicated that the sewage-fed vegetables of the Dhapa area, near the city of Calcutta, contain a very high amount of heavy metals. Currently 800 ha of land is being utilised throughout the year to cultivate more than eight types of vegetables, with a production of about 147 tonnes per day. A major population of Calcutta consumes these vegetables grown in the Dhapa area. Recently there has been huge pressure on the State Government to ban vegetables grown in the Dhapa area for human consumption. For this reason, we have studied the genotoxic effects of some of the most commonly used vegetable extracts from the Dhapa area after in vivo acute exposure in mice as measured by chromosomal aberrations (CA) and sister chromatid exchanges (SCE) to find out the minimum threshold dose to induce CA and SCE. Three different concentrations of the three most commonly used vegetable extracts (cauliflower, spinach, radish) were fed by gavage to mice for the study of CA and SCE. A significant increase in CA was observed only at the highest concentration of all the vegetable extract-treated groups when compared with the solvent control. A significant increase in SCE were observed in the middle and high doses of spinach and only the high dose of cauliflower and radish extract-treated series when compared with distilled water control. The lowest dose was equivalent to approximately 1 kg of vegetables consumed by a human (60 kg body weight) in a day. The middle and high doses of each vegetable extract were much higher than the normal amount of vegetables that a human can consume per day. So the minimum dose for inducing SCE and CA was much higher than the amount a human can consume in a day. Therefore this study indicates that these vegetables are safe for human consumption up to a certain limit, and attention should be given to reducing the heavy metal contents in the soil and sewage of the Dhapa area to thus reduce the heavy metal concentrations in the vegetables.     

Effect of hydrocele on testis and spermatogenesis

One hundred and twenty cases of big unilateral hydrocele of the tunica vaginalis testis have been studied to ascertain the effect on the structure and function of the testis, taking the normal side as control. There was no pressure effect from the hydrocele on the structure of the testis in 70 per cent, a flattening of testis in 22 per cent, and atrophy of testis in 8 per cent of cases. There was partial arrest of spermatogenesis in 10 per cent and total arrest of spermatogenesis in 8 per cent of cases. The remaining 82 per cent showed normal spermatogenesis.     

Fibromuscular dysplasia of the arteries of the leg. Apropos of 1 case

A 40 year old man presented fibromuscular hyperplasia of posterior tibial artery media, a rare lesion, and only exceptionally reported in the calves since a total of 3 cases were found in the literature.