Iron(III) and nickel(II) complexes of tetradentate thiosemicarbazones: Synthesis,structure, cytotoxicity,and lipophilicity

Eighteen of the iron(III) and nickel(II) complexes with tetradentate thiosemicarbazidato ligands were synthesized and described, by analytical and spectroscopic methods. Two complexes as an example to the iron and nickel centered ones were crystallographically analyzed to confirm the molecular structures. Cytotoxic effects of the complexes on K562 chronic myeloid leukemia cells were determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. For comparison, human umbilical vein endothelial cells (HUVECs) was used as a noncancerous cell line. While four of the iron(III) complexes exhibited the antileukemic effect with 50% inhibition of cell growth (IC₅₀) values in the 3.4 to 6.9 μg/mL range on K562 cell line, the nickel(II) complexes showed no significant effect on both cell lines. The complexes Fe4, Fe5, and Fe6, bearing 4‐methoxy substituent exhibited relatively high antiproliferative activity on both cell lines. Complex Fe3 with 3‐methoxy and S‐allyl groups exhibited a selectivity between K562 and HUVEC cells by IC₅₀ values of 6.9 and >10 μg/mL, respectively. Lipophilicity, a key parameter for bioavailability and oral administration, was found in the range of ?0.3 and +1.3 that desired for drug active ingredients. The results were discussed in the context of a structure‐activity relationship.     

Efficacy of Ankaferd Blood Stopper on bone healing in diabetic rats: a stereological and histopathological study

We evaluated the effects of Ankaferd Blood Stopper (ABS) and routine antibiotic prophylaxis (AP) on early healing of bone defects in diabetic rats. We used 48 rats in the study. Diabetes was induced in 24 rats using streptozotocin; the remaining 24 healthy untreated rats served as controls. Twelve of the diabetic rats and 12 of the healthy rats were treated with AP for 3 days before surgery. Bilateral bone defects were created in the mandible of all animals. ABS was applied to the defects on the left sides of the mandibles, while nothing was applied to the right sides. Animals were sacrificed on days 7 and 14 after operation and examined for histopathology and by stereology. The volume of newly formed bone was significantly less in the diabetic rats on both days 7 and 14. Local administration of ABS significantly increased the mean volume of newly formed bone in both diabetic and nondiabetic rats at days 7 and 14. No significant difference in new bone formation was found between AP and ABS treatment in diabetic rats. Both AP and local administration of ABS have beneficial effects on bone healing in diabetic animals.     

Laminar distribution of the cells of origin of the spinocerebral pathways involved in nociceptive transmission and pain modulation in the rat

The laminar distribution of spinomesencephalic, spinothalamic, and spinotelencephalic tract neurons, and the pattern of axonal collateralization in these spinocerebral pathways were studied in the rat by means of retrograde double-labelling of the cells with fluorescent dyes Fluoro-Gold and Primuline O. We found that sources of spinocerebral pathways to the analgesic brainstem centers, as well to thenucl. accumbens and septal nuclei, were mixed together in the marginal zone (lamina I, by Rexed), in the deep dorsal horn (laminae IV–VI), in the area around the central canal (lamina X), and within the lateral spinal nucleus. At the same time, all the above pathways retain their own specific projection fields. Thus, these spinocerebral projections could be characterized as extensive, but not diffuse. We propose that the main effect of activation of the direct spinal inputs to the limbic system is an increase in nociceptive sensitivity, but not a suppression of nocicptive transmission at the the spinal cord level.Neirofiziologiya/Neurophysiology, Vol. 28, No. 2/3, pp. 141–150, March–June, 1996.     

Capillary electrophoresis of methotrexate polyglutamates and its application in evaluation of γ-glutamyl hydrolase activity

A rapid and sensitive procedure for the separation of methotrexate (MTX) polyglutamates² using capillary electrophoresis (CE) is described as it applies to the in vitro assay of the enzyme γ-glutamyl hydrolase (GGH, EC 3.4.22.12). Distinct separation of MTX and polyglutamylated forms (up to glu₄) is achieved within 10 min using a 75 μm I.D. capillary (50 cm, +25 kV), and enables quantitation of both reactant and enzyme products. As activity can be reliably determined using less than 5×10⁵ eukaryotic cells, this new technique can be used to measure GGH in patient tumor samples and investigate the relationship between GGH levels and clinical MTX resistance.     

Antimicrobial peptides (AMPs): A promising class of antimicrobial compounds

Antimicrobial peptides (AMPs) are compounds, which have inhibitory activity against microorganisms. In the last decades, AMPs have become powerful alternative agents that have met the need for novel anti-infectives to overcome increasing antibiotic resistance problems. Moreover, recent epidemics and pandemics are increasing the popularity of AMPs, due to the urgent necessity for effective antimicrobial agents in combating the new emergence of microbial diseases. AMPs inhibit a wide range of microorganisms through diverse and special mechanisms by targeting mainly cell membranes or specific intracellular components. In addition to extraction from natural sources, AMPs are produced in various hosts using recombinant methods. More recently, the synthetic analogues of AMPs, designed with some modifications, are predicted to overcome the limitations of stability, toxicity and activity associated with natural AMPs. AMPs have potential applications as antimicrobial agents in food, agriculture, environment, animal husbandry and pharmaceutical industries. In this review, we have provided an overview of the structure, classification and mechanism of action of AMPs, as well as discussed opportunities for their current and potential applications.     

Dual function of the Drosophila Alk1/Alk2 ortholog Saxophone shapes the Bmp activity gradient in the wing imaginal disc

Wing patterning in Drosophila requires a Bmp activity gradient created by two Bmp ligands, Gbb and Dpp, and two Bmp type I receptors, Sax and Tkv. Gbb provides long-range signaling, while Dpp signals preferentially to cells near its source along the anteroposterior (AP) boundary of the wing disc. How each receptor contributes to the signaling activity of each ligand is not well understood. Here, we show that while Tkv mediates signals from both Dpp and Gbb, Sax exhibits a novel function for a Bmp type I receptor: the ability to both promote and antagonize signaling. Given its high affinity for Gbb, this dual function of Sax impacts the function of Gbb in the Bmp activity gradient more profoundly than does Dpp. We propose that this dual function of Sax is dependent on its receptor partner. When complexed with Tkv, Sax facilitates Bmp signaling, but when alone, Sax fails to signal effectively and sequesters Gbb. Overall, our model proposes that the balance between antagonizing and promoting Bmp signaling varies across the wing pouch, modulating the level and effective range, and, thus, shaping the Bmp activity gradient. This previously unknown mechanism for modulating ligand availability and range raises important questions regarding the function of vertebrate Sax orthologs.     

Clinical and electrophysiologic findings in dialysis patients

The aim of this study was to quantitatively determine the electrophysiologic changes occurring in the peripheral nerves and muscles in patients with chronic renal failure (CRF) treated with haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD), and to determine which electrophysiologic parameters are most commonly abnormal in uraemic patients. We investigated the relationship between the parameters of neurography and quantitative electromyography (QEMG) and clinical findings.The study included 42 patients with CRF (30 on HD and 12 on CAPD). Nerve conduction studies (NCSs) of the median, ulnar, tibial, peroneal, and sural nerves, and QEMG of the tibialis anterior and biceps brachii muscles were performed.We found axonal and/or demyelinating polyneuropathies in 97.6% of the patients (100% of HD and 91.7% of CAPD patients), but were not able to verify any significant differences between the HD and CAPD patients using NCS or QEMG. Median, ulnar, sural sensory nerve action potential (SNAP) amplitudes, peroneal CV and F-latency were the most common abnormal parameters in sensory and motor NCSs, respectively. The clinical findings only correlated with the parameters of neurography, and not with the parameters of QEMG. Sural SNAP amplitudes, peroneal and tibial CVs, F-latencies also correlated with the severity of the clinical findings in these patients, suggesting that these parameters can be used in follow up studies in these patients.In this study, most of the uraemic patients were found to have already mild or moderate neuropathies in which the objective clinical signs might be absent, even if they have some clinical symptoms. NCS showed abnormality indicating polyneuropathy in 24 out of 25 patients with clinical neuropathy signs and in 17 out of 17 patients with no clinical signs. Thus, in subclinical conditions NCS is useful to detect the abnormalities in peripheral nerves of the ureamic patients under chronic dialysis.     

Poly(glycidylmethacrylate) brushes generated on poly(VBC) beads by SI-ATRP technique: Hydrazine and amino groups functionalized for invertase adsorption and purification

Crosslinked-poly(vinylbenzylchloride), poly(VBC), beads were prepared by suspension polymerization and poly(glycidylmethacrylate) was grafted by surface-initiated-atom radical polymerization (SI-ATRP) technique. Epoxy groups of the grafted poly(GMA) were reacted with hydrazine and ammonia to create an affinity binding sites. The hydrazine and amine functionalized poly(VBC-g-GMA) beads were used as an affinity support for adsorption of invertase from solution and yeast crude extract. The influence of pH, equilibrium time, ionic strength and initial invertase concentration on the adsorption capacities of both hydrazine and amine functionalized beads has been investigated. Maximum invertase adsorptions onto hydrazine and amine functionalized beads, were 86.7 and 30.4 mg/g at pH 4.0 and 5.5, respectively. The experimental equilibrium data fitted well to the Temkin isotherm model. Finally, the hydrazine functionalized poly(VBC-g-GMA) beads were used for the purification of invertase from crude yeast extract in a batch system and the purity of the eluted invertase from the hydrazine functionalized beads was determined as 92% by HPLC from single step purification protocol.     

Anti-inflammatory and antinociceptive potential of major phenolics from Verbascum salviifolium Boiss

The potential effects of flavonoids, phenylethanoid and neolignan glycosides from the aerial parts of Verbascum salviifolium Boiss. were studied in the p-benzoquinone-induced writhing reflex, for the assessment of the antinociceptive activity, and in carrageenan- and PGE1-induced hind paw edema and 12-O-tetradecanoyl-13-acetate (TPA)-induced ear edema models in mice, for the assessment of the anti-inflammatory activity. Through bioassay-guided fractionation and isolation procedures ten compounds from the aqueous extract of the plant, luteolin 7-O-glucoside (1), luteolin 3'-O-glucoside (2), apigenin 7-O-glucoside (3), chrysoeriol 7-O-glucoside (4), beta-hydroxyacteoside (5), martynoside (6), forsythoside B (7), angoroside A (8), dehydrodiconiferyl alcohol-9'-O-beta-D-glucopyranoside (9) and dehydrodiconiferyl alcohol-9-O-beta-D-glucopyranoside (10), were isolated and their structures were elucidated by spectral techniques. Results have shown that 1, 2, 3 and 5 significantly inhibited carrageenan-induced paw edema at a 200 mg/kg dose, while 1, 2 and 5 also displayed anti-inflammatory activity against the PGE1-induced hind paw edema model. However, all the compounds showed no effect in the TPA-induced ear edema model. The compounds 1 and 2 also exhibited significant antinociceptive activity.