Syntheses, characterization and in vitro antiamoebic activity of new Pd(II) complexes with 1-N-substituted thiocarbamoyl-3,5-diphenyl-2-pyrazoline derivatives

Reaction of neutral NS bidentate ligands, 1-N-substituted thiocarbamoyl-3,5-diphenyl-2-pyrazolines, isolated by cyclization of chalcone with N-4-substituted thiosemicarbazide of aromatic amines (1-8), with [Pd(DMSO)(2)Cl(2)] (DMSO=dimethylsulfoxide) leads to the formation of new complexes of the type [Pd(L)Cl(2)] (1a-8a). The structures of the compounds were elucidated by UV, IR, (1)H NMR, (13)C NMR and ESI-MS spectral data and thermogravimetric analysis and their purities were confirmed by elemental analyses. The antiamoebic activity of these complexes was evaluated by microdilution method against HM1:IMSS strain of Entameoba histolytica and the results were compared with the standard drug, metronidazole. Generally palladium complexes showed better activity than their corresponding ligands. Compound 3a showed better IC(50)=0.05 microM as compared to metronidazole IC(50)=1.82 microM.     

Influence of isolation on the recovery of pond mesocosms from the application of an insecticide. I. Study design and planktonic community responses

The influence of relative isolation on the ecological recovery of freshwater outdoor mesocosm communities after an acute toxic stress was assessed in a 14-month-long study. A single concentration of deltamethrin was applied to 8 out of 16 outdoor 9-m3 mesocosms to create a rapid decrease of the abundance of arthropods. To discriminate between external and internal recovery mechanisms, four treated and four untreated (control) mesocosms were covered with 1-mm mesh screen lids. The dynamics of planktonic communities were monitored in the four types of ponds. The abundance of many phytoplankton taxa increased after deltamethrin addition, but the magnitude of most increases was relatively small, probably due to low nutrient availability and the survival of rotifers. The greatest impact on zooplankton was seen in Daphniidae and, to a lesser extent, calanoid copepods. Recovery (defined as when statistical analysis failed to detect a difference in the abundance between the deltamethrin-treated ponds and corresponding control ponds for two consecutive sampling dates) of Daphniidae was observed in the water column 105 and 77 d after deltamethrin addition in open and covered mesocosms, respectively, and <42 d for both open and covered ponds at the surface of the sediments. Rotifers did not proliferate, probably because of the survival of predators (e.g., cyclopoid copepods). These results confirm that the recovery of planktonic communities after exposure to a strong temporary chemical stress mostly depends upon internal mechanisms (except for larvae of the insect Chaoborus sp.) and that recovery dynamics are controlled by biotic factors, such as the presence of dormant forms and selective survival of predators.     

Significance of bacteria in the mucilage phenomenon in the northern Adriatic Sea

Episodes of massive mucilage formation in the northern Adriatic Sea have been recorded for over a century but their cause is still a matter of conjecture and debate. It is generally thought that mucilage forms due to copious polysaccharide exudation by phosphorus limited algae. In this paper we develop the thesis that bacteria play major roles in mucilage formation. We argue that mucilage is largely produced as a consequence of bacteria-organic matter interactions and bacterial capsular polysaccharide synthesis. Ectohydrolytic enzymes of bacteria are critical in producing long-lived polysaccharides. Further, bacteria cause efficient P regeneration, particularly intensely in microscale features e.g. phycospheres, detritus and aggregates. Bacteria thus help sustain high rates of primary production despite vanishingly low levels of phosphorus in the bulk phase seawater. We integrate these roles of bacteria into a conceptual model which emphasizes microscale interactions of microbes within a seawater gel matrix as the basis for a mechanistic understanding of the accumulation of long-lived polysaccharide to form mucilage.     

Anti-inflammatory,analgesic and antiamoebic activity evaluation of pyrimido[1,6-a]benzimidazole derivatives synthesized by the reaction of ketoisothiocyanates with mono and diamines

(UN) substituted o-phenylenediamines 1a-g reacted with 3-isothiocyanatobutanal to give pyrimidobenzimidazole derivatives, 2a-g, respectively. Products 4, 6 and 8, 10 were obtained by condensation of 3-isothiocyanatobutanal with 2,3-diaminopyridine, 1,4-diaminobutane and 3-isothiocyanatopropanal with 4,5-dimethyl-1,2-phenylenediamine, o-nitroaniline, respectively. S-Methylation of 2f and 11b gave products 12a and 12b, respectively. Anti-inflammatory and analgesic activity evaluations of 2a-g and 12b were carried out at 50 mg kg(-1) p.o. Compound 2c exhibited good anti-inflammatory (46%) and mild analgesic activity (50%). Antiamoebic activity evaluations (using microdilution method) of 2a-g against Entamoeba-histolytica (strain HM1: IMSS) were carried out and compounds 2a, 2b, 2d and 2g exhibited good antiamoebic activity in vitro.     

Synthesis and calcium antagonist activity of 1,4-dihydropyridines containing phenylaminoimidazolyl substituents

Alkyl ester analogues of nifedipine, in which the ortho-nitrophenyl group at position 4 is replaced by 2-methylthio-1-phenylamino-5-imidazolyl substituent, were synthesized and evaluated as calcium-channel antagonists using the high K(+) contraction of guinea-pig ileal longitudinal smooth muscle. The results for the symmetrical esters showed that in the series of alkyl esters increasing the length of methylene chain in C-3 and C-5 ester substituents for more than two methylene units decreases activity. In the phenylalkyl ester series increasing the length of methylene chain also decreases activity. The results demonstrate that most of the compounds had similar activity to the reference drug nifedipine. In addition, two compounds, 5b and 5f were more active than the nifedipine.     

Role of nitric oxide in the acquisition and expression of apomorphine- or morphine-induced locomotor sensitization

In the present study, the effects of L-arginine, a nitric oxide (NO) precursor, and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on apomorphine- or morphine-induced locomotor sensitization in male albino mice were investigated. Our data showed that subcutaneous (s.c.) injection of apomorphine (2-10 mg/kg) or morphine sulphate (5-50 mg/kg) significantly increased locomotor behaviour in a dose-dependent manner. Intraperitoneal (i.p.) administration of L-arginine (100 mg/kg) increased locomotor activity, whereas L-NAME (20 mg/kg) decreased it. L-Arginine and L-NAME increased and decreased apomorphine- or morphine-induced locomotions, respectively. The locomotor behavioural response was enhanced in mice pretreated with apomorphine (2 mg/kg, daily x3 days) or morphine (10 mg/kg, daily x3 days) alone, indicating that sensitization had developed. Administration of L-arginine 30 min before each of three daily doses of apomorphine or morphine increased the development of sensitization, while administration of L-NAME 30 min before each of three daily doses of apomorphine or morphine decreased the acquisition of sensitization induced by apomorphine or morphine. Administration of L-arginine significantly increased and L-NAME significantly and dose-dependently decreased the expression of both apomorphine- and morphine-induced sensitization. The results indicate that NO may be involved in the acquisition and expression of apomorphine- or morphine-induced sensitization.     

Co-expression of NaVβ subunits alters the kinetics of inhibition of voltage-gated sodium channels by pore-blocking μ-conotoxins

Background and Purpose

Voltage-gated sodium channels (VGSCs) are assembled from two classes of subunits, a pore-bearing α-subunit (Na_V1) and one or two accessory β-subunits (Na_Vβs). Neurons in mammals can express one or more of seven isoforms of Na_V1 and one or more of four isoforms of Na_Vβ. The peptide μ-conotoxins, like the guanidinium alkaloids tetrodotoxin (TTX) and saxitoxin (STX), inhibit VGSCs by blocking the pore in Na_V1. Hitherto, the effects of Na_Vβ-subunit co-expression on the activity of these toxins have not been comprehensively assessed.

Experimental Approach

Four μ-conotoxins (μ-TIIIA, μ-PIIIA, μ-SmIIIA and μ-KIIIA), TTX and STX were tested against Na_V1.1, 1.2, 1.6 or 1.7, each co-expressed in Xenopus laevis oocytes with one of Na_Vβ1, β2, β3 or β4 and, for Na_V1.7, binary combinations of thereof.

Key Results

Co-expression of Na_Vβ-subunits modifies the block by μ-conotoxins: in general, Na_Vβ1 or β3 co-expression tended to increase k_on (in the most extreme instance by ninefold), whereas Na_Vβ2 or β4 co-expression decreased k_on (in the most extreme instance by 240-fold). In contrast, the block by TTX and STX was only minimally, if at all, affected by Na_Vβ-subunit co-expression. Tests of Na_Vβ1 : β2 chimeras co-expressed with Na_V1.7 suggest that the extracellular portion of the Na_Vβ subunit is largely responsible for altering μ-conotoxin kinetics.

Conclusions and Implications

These results are the first indication that Na_Vβ subunit co-expression can markedly influence μ-conotoxin binding and, by extension, the outer vestibule of the pore of VGSCs. μ-Conotoxins could, in principle, be used to pharmacologically probe the Na_Vβ subunit composition of endogenously expressed VGSCs.     

The impact of disease on family members: a critical aspect of medical care

Most existing health-related quality of life research concerns the impact of disease on patients. However, in several medical specialties including dermatology, oncology, and physical and mental disability, studies have been carried out investigating the impact of disease on the lives of families of patients. The aim of this paper is to review the literature which relates to the impact of disease on family members of patients. The OVIDSP Medline was selected as the primary database, Searches were limited to sources published in English. 158 papers were identified for review. The definition of “family” varied across the literature, and a broad definition was accepted in this review. This review shows that a wide variety of aspects of family members’ lives can be affected, including emotional, financial, family relationships, education and work, leisure time, and social activities. Many of these themes are linked to one another, with themes including financial impact and social impact being linked to emotional impact. Some positive aspects were also identified from the literature, including family relationships growing stronger. Several instruments exist to measure the impact of illness on the family, and most are disease or specialty- specific. The impact of disease on families of patients is often unrecognised and underestimated. Taking into account the quality of life of families as well as patients can offer the clinician a unique insight into issues such as family relationships and the effect of treatment decisions on the patient''s close social group of partner and family.     

Effect of fluid contamination on reverse torque values in implant-abutment connections under oral conditions

PURPOSEImplant mechanical complications, including screw loosening, can influence dental implant success. It has been shown that torque values are affected by contamination occurred in implant-abutment (I/A) interface. This study aimed to examine the effects of blood, saliva, fluoride and chlorhexidine contamination on reverse torque values (RTVs) of abutment screws in oral conditions.MATERIALS AND METHODS50 fixtures were mounted into the stainless-steel holders and divided into five groups (n = 10). Except control group (NC), fixture screw holes in other groups were contaminated with chlorhexidine (CG), saliva (SG), blood (BG), or fluoride (FG). Abutment screws were tightened with a digital torque meter. I/A assemblies were subjected to thermocycling and cyclic loading. The mean RTVs were recorded and data were analyzed with one-way ANOVA and Tukey test.RESULTSExcept for specimens in SG (20.56 ± 1.33), other specimens in BG (21.11 ± 1.54), CG (22.89 ± 1.1) and FG (24.00 ± 1.12) displayed significantly higher RTVs compared to NC (19.00 ± 1.87). The highest RTVs were detected in CG and FG.CONCLUSIONThe obtained data robustly suggest that RTVs were significantly affected by fluid contaminations. Specimens in FG and CG displayed the highest RTVs. Therefore, clinicians should have enough knowledge about probable contaminations in I/A interface in order to manage them during clinical procedure and to inform patients about using oral care products.