Improved efficiency and stability of secnidazole – An ideal delivery system

Secnidazole (α,2-Dimethyl-5-nitro-1H-imidazole-1-ethanol) is a highly effective drug against a variety of G⁺/G⁻ bacteria but with significant side effects because it is being used in very high concentration. In this study, gold nanoparticles (GNP_S) were selected as a vehicle to deliver secnidazole drug at the specific site with more accuracy which made the drug highly effective at substantially low concentrations. The as-synthesized GNPs were capped with Human Serum Albumin (HSA) and subsequently bioconjugated with secnidazole because HSA provides the stability and improves the solubility of the bioconjugated drug, secnidazole. The quantification of covalently bioconjugated secnidazole with HSA encapsulated on enzymatically synthesized GNPs was done with RP-HPLC having SPD-20 A UV/VIS detector by using the C-18 column. The bioconjugation of GNPs with secnidazole was confirmed by Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The bioconjugated GNPs were characterized by UV–VIS spectroscopy, TEM, Scanning Electron Microscopy (SEM) and DLS. Zeta potential confirmed the stability and uniform distribution of particles in the emulsion of GNPs. The separation of bioconjugated GNPs, unused GNPs and unused drug was done by gel filtration chromatography. The minimal inhibitory concentration of secnidazole-conjugated gold nanoparticles (Au-HSA-Snd) against Klebsiella pneumonia (NCIM No. 2957) and Bacillus cereus (NCIM No. 2156) got improved by 12.2 times and 14.11 times, respectively, in comparison to pure secnidazole. Precisely, the MIC of Au-HSA-Snd against K. pneumonia (NCIM No. 2957) and B. cereus (NCIM No. 2156) were found to be 0.35 and 0.43 μg/ml, respectively whereas MIC of the pure secnidazole drug against the same bacteria were found to be 4.3 and 6.07 μg/ml, respectively.     

Influence of aluminium on the immune system – an experimental study on volunteers

The purpose of this study was to examine whether oral exposure to aluminum (Al) can affect the human immune system. Eighteen healthy volunteers (mean age 42, 28–57 yr) were divided into a test group (9 females, 4 males) and a referent group (3 females, 2 males). Over 6 weeks, the test subjects ingested 10 ml of antacid (aluminum hydroxide, 59 mg Al/ml) three times daily. Aluminum was analyzed in urine before and during the exposure period (ICP-MS). Blood samples were used for analysis of lymphocyte subpopulations, mitogen-induced lymphocyte proliferation and in vitro production and circulating plasma concentrations of immunoglobulin (Ig) A, IgG, IgM, interleukin (IL) -2 and IL-4. Urinary Al concentration in the test subjects was approximately 10- to 20-fold higher than in the referent group during exposure. This indicates that ingestion of an Al-containing antacid is associated with an Al absorption far above that originating from food and drinking water. In both referents and test subjects the lymphocyte subpopulations, lymphocyte proliferation and the in vitro Ig and IL production showed similar, time-dependent changes before as well as during the exposure period. No major differences were seen between the referent and test groups regarding the immune parameters, except for a slightly smaller CD8+CD45R0+ population (primed cytotoxic T-cells), in the exposed individuals as compared to the referents. The results also show that subjects on antacid therapy may constitute a suitable population for studying biological effects of high-dose oral exposure to Al.     

Terrestrial natural sources of trichloromethane (chloroform, CHCl3) – An overview

The widespread use of volatile chlorinatedcompounds like chloroform, trichloroethene andtetrachloroethene in industrialized societiescauses a large annual release of thesecompounds into the environment. Due to theirrole as a source for halogen radicals involvedin various catalytic atmospheric reactioncycles, including the regulation of thestratospheric and tropospheric ozone layers,these compounds also constitute a risk fordrinking water resources as they can betransported to the groundwater fromcontaminated field sites or even fromatmospheric deposition. Therefore,identification and investigation of sources andsinks of volatile chlorinated compounds are ofparticular interest. Chloroform, a majorcontributor to natural gaseous chlorine, wasfound to be emitted by several anthropogenicand natural sources including the oceans andterrestrial areas. The origin of chloroform inthe terrestrial environment can beanthropogenic point sources, atmosphericdeposition, release by vegetation andproduction directly in the soil. The calculatedannual biogenic global chloroform emission is700 Gg, and marine and terrestrial environmentsare nearly equal contributors. The estimatedemissions from anthropogenic sources accountfor less than 10% of the estimated totalemissions from all sources. Among terrestrialsources, forests have recently been identifiedas contributing to the release of chloroform intothe environment. With the data available,annual emissions of chloroform to theatmosphere from forest sites were calculatedand compared to other natural sources. Atpresent knowledge, forests are only a minorsource in the total biogenic flux ofchloroform, contributing less than 1% to theannual global atmospheric input. However, itshould be noted that data are available forNorthern temperate forests only. The largetropical forest areas may provide a yet unknowninput of chloroform.     

An electron microscope study of spermiogenesis in Spirorbis (Laeospira) mörchi Levinsen (Polychaeta)

Summary 1. In the hermaphroditic polychaete Spirorbis (Laeospira) mörchi, early spermatids develop in clusters within the coelom of the male segments. The cells within a single cluster are all in the same stage of development and are connected by an extensive cytoplasmic bridge system. 2. The acrosome forms in a single lamella of the Golgi apparatus which bears a close association to the plasma membrane. The final position of the acrosome is at a point considerably removed from the site of formation. 3. The nuclear changes culminating in condensation and elongation of the head are described. A rearrangement of cytoplasmic microtubules occurs simultaneously with nuclear elongation. 4. Redundant nuclear envelope, resulting from nuclear volume reduction, is pinched off in the form of four vesicles. The latter structures are lost with the residual cytoplasm. 5. Pour spherical mitochondria elongate to become incorporated into the middle-piece. A rearrangement of microtubules also occurs simultaneously with mitochondrial elongation. Cytoplasmic microtubules are absent from the fully formed sperm.This investigation was made possible through a Postdoctoral Fellowship from the National Science Foundation, 44150. — I wish to express my gratitude to Dr. John Luft for the training I received in the techniques of electron microscopy. Dr. James Koehler and Dr. Daniel Szollosi are thanked for their many helpful suggestions.     

Near-bottom performance of the Acoustic Doppler Velocimeter (ADV) – a comparative study

In a laboratory flume, a comparative study on the near-bottom performance of the Acoustic Doppler Velocimeter (ADV) was conducted. Two different ADV systems were tested for different configurations and two flow velocities (9 cm s⁻¹, 18 cm s⁻¹). The results were compared with synchronous measurements with a Laser Doppler Anemometer (LDA). Near-bottom velocity measurements with the ADV have to be interpreted carefully as the ADV technique underestimates flow velocities in a zone close to the sediment. The height of this zone above the sediment varies with different ADV systems and configurations. The values for nominal sampling volume height (SVH) given by the software often underestimate the true, effective sampling volume heights. Smaller nominal SVH improve the ADV near-bottom performance, but the vertical extent of the zone in which the ADV underestimates flow by more than 20% may be larger than true SVH/2 by a factor of 2 (=true SVH). When the measurement volume approaches the bottom, ADV data quality parameters (signal-to-noise-ratio (SNR) and signal amplitude) exceeding the average ‘open water’ level, are clear indicators that the ADV has begun to underestimate the flow velocity. Unfortunately, this is not a safe indicator for the range of reliable measurements as the ADV may begin to underestimate velocities even with unchanged ‘open water’ data quality parameters. Thus, one can only recommend avoiding measurements below a distance from the bottom that was defined empirically comparing the ADV and the LDA velocity profiles. This distance is 2.5 times nominal sampling volume height for the tested ADV systems and experimental settings.     

Metformin increases liver accumulation of vitamin B12 – An experimental study in rats

Aims/hypothesis

Patients treated with metformin exhibit low levels of plasma vitamin B₁₂ (B₁₂), and are considered at risk for developing B₁₂ deficiency. In this study, we investigated the effect of metformin treatment on B₁₂ uptake and distribution in rats.

Methods

Sprague Dawley rats (n = 18) were divided into two groups and given daily subcutaneous injections with metformin or saline (control) for three weeks. Following this, the animals received an oral dose of radio-labeled B₁₂ (⁵⁷[Co]-B₁₂), and urine and feces were collected for 24 h. Plasma, bowel content, liver, and kidneys were collected and analyzed for B₁₂, unsaturated B₁₂-binding capacity, and ⁵⁷[Co]-B₁₂.

Results

Three weeks of metformin treatment reduced plasma B₁₂ by 22% or 289 [47-383] pmol/L (median and [range]) (p = 0.001), while no effect was observed on unsaturated B₁₂-binding capacity. Compared with controls, the amount of B₁₂ in the liver was 36% (p = 0.007) higher in metformin-treated rats, while the B₁₂ content in the kidney was 34% (p = 0.013) lower. No difference in the total amount of absorbed ⁵⁷[Co]-B₁₂ present in the tissues and organs studied was found, suggesting that metformin has no decreasing effect on the B₁₂ absorption.

Conclusions/interpretation

These results show that metformin treatment increases liver accumulation of B₁₂, thereby resulting in decreases in circulating B₁₂ and kidney accumulation of the vitamin. Our data questions whether the low plasma B₁₂ observed in patients treated with metformin reflects impaired B₁₂ status, and rather suggests altered tissue distribution and metabolism of the vitamin.     

Dynamics of trace metals in the system water – soil – plant – wild rats – tapeworms (Hymenolepis diminuta) in Maglizh area,Bulgaria

BackgroundThe impact of chemical elements on the biosphere is a function of their concentration and chemical form. Elucidation and prognosing of the latters in water basins and soil extracts is of particular significance for the assessment of their bioaccumulation in plants and animals.ObjectivesTrace metals dynamics in the system water – soil–plant–wild rats – Hymenolepis diminuta in two agro-industrial zones (East and West) around Maglizh city, Bulgaria were investigated through experimental studies and thermodynamic modelling of the chemical species.MethodsSamples from surface waters of rivers, their nearby uncultivated soils, meadow uncultivated vegetation (Ranunculus acris and Gramineae) and field rats were collected. In situ measurements and laboratory analyses were performed for the determination of the physico-chemical characteristics and total concentrations of Al, Fe, Mn, Ni, Cu, Zn and Pb. The distribution of their dissolved chemical species in water samples and in the aqueous soil extracts was calculated using a thermodynamic approach. The relationship chemical species - bioaccumulation was discussed.ResultsWaters and soils in the East zone of Maglizh area were found to be more polluted compared to those in the West one, regarding Ni, Mn, Zn, Pb and Cu, while Mn and Cu displayed the highest mobility in West zone soils. Trace metals contents in Ranunculus acris exceed that in Gramineae, since the highest accumulation factors were calculated for Cu and Zn. The highest accumulation in rats was found for Zn followed by Cu, being higher in the West zone. Thermodynamic modelling shows that Mn²⁺ free ions are dominant in both waters and aqueous soil extracts. Ni²⁺ and Zn²⁺ ions followed by metal-organic complexes are dominant in waters of East zone while metal-organic complexes followed by free ions are dominant in waters of West zone and both soil extracts. Metal-organic complexes are dominant for Fe, Cu and Pb in all samples studied, while mainly hydroxy forms (Al(OH)₄⁻) followed by metal-organic complexes are typically for Al depending on pH.ConclusionsExperimentally established bioaccumulation of trace metals in the studied vegetation and rats is a consequence of the total concentration of trace metals in waters and soils, their mobility and chemical species. The dominance of organic complexes of trace metals is a prerequisite for their bioaccumulation in plants. Rats are in direct contact with the soil solution and therefore, of importance is the content of free ions of Mn²⁺, Ni²⁺, Zn²⁺, which are easily absorbed through the skin. The host-helminth system wild rat/H. diminuta could be used as a bioindicator for trace metals pollution.     

Recovery of grassland after clear-cutting of invasive Robinia pseudoacacia – Long-term study in Prague (Czech Republic)

Invasive species belong to the main threats to dry grassland biodiversity. That́s why nature conservation managers seek the best ways to remove them and to support the restoration process of original natural habitats. We studied the effect of clear-cutting of invasive black locust (Robinia pseudoacacia L.) on the recovery of former species rich dry grassland vegetation. Ten permanent plots where R. pseudoacacia was cut down were long-term monitored in nature reserves protecting dry grasslands. The representation of dry grassland plants has been increased four times and the representation of synanthropic plants has been decreased two times during 40 years of succession even though R. pseudoacacia still relatively successfully resisted eradication efforts. During the succession after R. pseudoacacia cutting down, the Ellenberg indicator values for nutrients have decreased significantly, but no decrease in the nitrate content of the soil was observed. The long-term monitoring revealed that the restoration of dry grasslands invaded by R. pseudoacacia is possible but very time consuming.     

Biomimetic Total Synthesis of ( – )-Aplysistatin

A biomimetic synthesis of ( – )-aplysistatin (1) is described. The Wittig reaction of the keto ester 5 with homogeranyl triphenylphosphonium ylid gave the desired intermediate 3. Successive treatment of 3 with activated manganese dioxide, sodium chlorite and aq. trifluoroacetic acid led to the unsaturated β-hydroxy lactone 2, which was subjected to brominative cyclization to yield ( –)-aplysistatin (1).     

An estimate of the costs of an effective system of protected areas in the Niger Delta – Congo Basin Forest Region

This paper presents an analysis of the costs of implementing a biodiversity conservation vision for the Niger Delta – Congo Basin Forest Region, a region covering the forests from Nigeria across Cameroon, Equatorial Guinea (EG), Gabon, Central African Republic (CAR), Congo and the Democratic Republic of Congo (DRC), based on an effectively managed and representative protected area network. The Niger Delta – Congo Basin Forest Region has an existing protected area system of about 135,000km². A system of effectively managed protected areas that would maintain a substantial part of the biodiversity would require an additional 76,000km² to be gazetted and an investment for the total system of over $1 billion (10⁹). After this initial 10-year investment an estimated $87 million a year would be sufficient to maintain this system. Overall, current donor expenditure in the present network is probably less than $15 million per year, so over $800 million dollars will have to be found elsewhere. If the international community values the biodiversity of the Niger Delta – Congo Basin Forest Region, it is going to have to cover the cost of maintaining this biodiversity.     

In vivo anticoccidial activity of berberine [18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo(5,6-a) quinolizinium] – An isoquinoline alkaloid present in the root bark of Berberis lycium

Coccidiosis, caused by various Eimeria species, is a major parasitic disease in chicken. However the increasing resistance of these parasites to currently used anticoccidial drugs has stimulated the search for new methods of control. As part of this effort we investigated the root bark of Berberis lycium (barberry) as a potential source of compounds with anticoccidial activity. In the present study anticoccidial activity of different solvent extracts of the root bark of B. lycium and berberine was evaluated in vivo using broiler chicken. Results of the study demonstrated equipotent efficacy of pure berberine in comparison to that of standard drug amprolium on the basis of reduction in coccidian oocyst output, body weight gain of chicken and feed conversion ratio. Among the extracts crude methanolic extract showed highest anticoccidial activity tested at 300 mg/kg body weight which could be due to the presence of alcohol-soluble active ingredients in root bark of B. lycium. Toxicological studies revealed that B. lycium extracts as well as berberine were not lethal up to dosage of 2000 mg/kg body weight. LD⁵⁰ was not determined as mortalities were not recorded in any of the five groups of chicken. From the present study it can be concluded that root bark of B. lycium has the immense potential to contribute to the control of coccidian parasites of chicken. Our results corroborate the use of berberine for treatment of severe diarrhoea, amoebiasis and intestinal infections and could justify its use in folk medicine for treatment of haemorrhagic dysentery.     

The direction of shift-work rotation impacts metabolic risk independent of chronotype and social jetlag – An exploratory pilot study

The aim of this pilot study was to explore the risk of metabolic abnormalities in steel workers employed in different shift-work rotations. Male workers in a steel factory [16 employed in a fast clockwise rotation (CW), 18 in slow counterclockwise rotation (CC), 9 day workers (DW); mean age 43.3?±?SD 6.8 years] with at least 5 years experience in their current work schedule participated. All workers provided fasting blood samples between 06:00 and 08:00?h for plasma glucose, insulin, apo-lipoproteins A and B (ApoA, ApoB), high- and low-density lipoproteins (HDL and LDL), total cholesterol (tCH), triglycerides (TG), minimally oxidized (mox) LDL, C-reactive protein (CRP), interleukin-8 (IL-8) and serum 25-hydroxyvitamin D (25(OH)D). HOMA index (homeostatic model assessment) was calculated to evaluate insulin resistance, beta cell function and risk of diabetes. Information on demographics, health, stimulants, sleep, social and work life, chronotype (phase of entrainment) and social jetlag (difference between mid-sleep on workdays and free days) as a surrogate for circadian disruption was collected by questionnaire. Neither chronotype nor social jetlag was associated with any of the metabolic risk blood markers. There were no significant differences in 25(OH)D, ApoA, ApoB, CRP, HDL, IL-8, insulin, LDL, mox-LDL, mox-LDL/ApoB ratio, tCH and TG levels between the three work groups. Although we did observe absolute differences in some of these markers, the small sample size of our study population might prevent these differences being statistically significant. Fasting glucose and HOMA index were significantly lower in CW compared to DW and CC, indicating lower metabolic risk. Reasons for the lower fasting glucose and HOMA index in CW workers remains to be clarified. Future studies of workers in different shift rotations are warranted to understand better the differential effects of shift-work on individual workers and their health indices.     

Finite element analysis of dental implant loading on atrophic and non-atrophic cancellous and cortical mandibular bone – a feasibility study

The first aim of this study was to assess displacements and micro-strain induced on different grades of atrophic cortical and trabecular mandibular bone by axially loaded dental implants using finite element analysis (FEA). The second aim was to assess the micro-strain induced by different implant geometries and the levels of bone-to-implant contact (BIC) on the surrounding bone. Six mandibular bone segments demonstrating different grades of mandibular bone atrophy and various bone volume fractions (from 0.149 to 0.471) were imaged using a micro-CT device. The acquired bone STL models and implant (Brånemark, Straumann, Ankylos) were merged into a three-dimensional finite elements structure. The mean displacement value for all implants was 3.1±1.2 µm. Displacements were lower in the group with a strong BIC. The results indicated that the maximum strain values of cortical and cancellous bone increased with lower bone density. Strain distribution is the first and foremost dependent on the shape of bone and architecture of cancellous bone. The geometry of the implant, thread patterns, grade of bone atrophy and BIC all affect the displacement and micro-strain on the mandible bone. Preoperative finite element analysis could offer improved predictability in the long-term outlook of dental implant restorations.     

Dry root rot (Rhizoctonia bataticola (Taub.) Butler): an emerging disease of chickpea – where do we stand?

Dry root rot caused by Rhizoctonia bataticola (Macrophomina phaseolina) of chickpea (Cicer arietinum L.) is gaining importance in the changed scenario of climate when growing crop is predisposed to high temperature and moisture stress. Being mainly a soil-inhabiting pathogen, many environmental and soil factors are responsible for the development of disease. No systematic research related to the biology, ecology and epidemiology of dry root rot in chickpea has been conducted so far. Research is needed to improve the identification and characterisation of variability within its epidemiological and pathological niches. Limited literature available on host plant resistance for dry root rot indicated lack of resistant sources for this disease. The present article discusses current status of the disease in the context of climate change and possible management options to alleviate the problem.