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A series of zinc(II) ([Zn(H2O)(L)Cl] (1)), copper (II) ([Cu(L)Cl] (2), [Cu(L)Br] (3), [Cu2(L)2(CH3COO)2]·4H2O (4)), nickel(II) ([Ni(HL)2]Cl2·H2O (5)), and cobalt(III) ([Co(L)2]Cl (6)) complexes were obtained with 2-formylpyridine N4-allylthiosemicarbazone (HL). In addition another two thiosemicarbazones (3-formylpyridine N4-allylthiosemicarbazone (HLa) and 4-formylpyridine N4-allylthiosemicarbazone (HLb)) have been obtained. The synthesized thiosemicarbazones have been studied using 1H and 13C NMR spectroscopy, IR spectroscopy, and X-ray diffraction analysis. The composition and structure of complexes were studied using elemental analysis, IR and UV-Vis spectroscopies, molar conductivity, and magnetic susceptibility measurements. Single crystal X-ray diffraction analysis elucidated the structure of thiosemicarbazones HL, HLa, and HLb, as well as complexes 4 and 5. The antiproliferative properties of these compounds toward a series of cancer cell lines (HL-60, HeLa, BxPC-3, RD) and a normal cell line (MDCK) have been investigated. The nickel complex shows high selectivity (SI > 1000) toward HL-60 cell line and is the least toxic. The zinc complex shows the highest selectivity toward RD cell line (SI = 640). The copper complexes (2–4) are the most active molecular inhibitors of proliferation of cancer cells, but exhibit not such a high selectivity and are significantly more toxic. Zinc and copper complexes manifest high antibacterial activity. It was found that calculated at B3LYP level of theory different reactivity descriptors of studied compounds strongly correlate with their biological activity. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases, with a variable probability of transformation into acute leukemia, which is, in the vast majority of cases, of myeloid lineage. Nevertheless, rare cases of acute lymphoblastic leukemia in patients with previously diagnosed MDS have been reported. We describe a series of 3 cases of MDS/CMML marked with evolution to acute lymphoblastic leukemia (ALL) and provide a comprehensive review of the 49 cases documented in the literature so far. These sporadic events have only been published as single-case reports or small series to date. Such atypical cases emphasize the possibility of major phenotypic switches arising at the leukemic stem cell (LSC) and/or early progenitor levels, as a consequence of epigenetic and genomic events driving these changes in the bone marrow niche. [ABSTRACT FROM AUTHOR]

The development of acute lymphoblastic leukemia (ALL) from myelodysplastic syndrome (MDS) is a very rare event. The current report presents a rare case of a 33‑year‑old man who was diagnosed with MDS with multiple‑lineage dysplasia (MDS‑MLD) that transformed into pro‑B‑ALL. A missense mutation (S1231F) of the additional sex combs like 1, transcriptional regulator gene was identified, which may have a substantial role in the progression, however does not act as an unfavorable prognostic marker. The patient died during induction chemotherapy. The present study further conducted an analysis on 30 patients to determine progression to ALL. Patients were predominantly male (76.7%, 23/30) with a median age of 56 years (3‑90 years). The median time to transformation was 5.5 months (2‑50 months). The most common type of MDS with ALL transformation comprised of MDS‑excess blasts (MDS‑EB; 40%, 12/30), MDS with single‑lineage dysplasia (MDS‑SLD; 30%, 9/30) and MDS with ring sideroblasts (MDS‑RS; 16.7%, 5/30). The majority of the patients transformed to B‑cell (66.7%, 16/24) followed by T‑cell (33.3%, 8/24) ALL. From the 25 cases where data was available, the complete remission rate was 75% (15/20) with ALL‑directed chemotherapy and the median remission duration was 15 months (range 4.5 to 51 months). However, the results indicated that ALL following MDS is characterized by a high rate of early death (20%, 5/25). [ABSTRACT FROM AUTHOR]

Background: HIV infection is characterized by replication by aberrant immune activation and persistent inflammation. HIV infection is associated with loss of CD4 T cells, resulting in dysfunction of immune system. Adenosine Deaminase (ADA) has a cytokine-like costimulatory role in T cell proliferation. Materials and Methods: The study included 150 HIV positive patients between age group of 20-50 years from ICTC (Integrated Counseling and Testing Centre) and ART centre of Belagavi Institute of Medical Sciences, Hospital, Belagavi, Karnataka, India. ADA activity and CD4 cell count were estimated before starting any treatment and after 3 months interval of ART upto 9 months. Serum ADA activity was estimated by using colorimetric method of Giusti and Galanti. Results and Discussion: The study showed increased ADA activity before ART, which was gradually decreasing after 3, 6 and 9 months of ART (p<0.001). We observed low CD4 cell count before ART, there was steady rise of CD4 cell count after 3, 6 and 9 months of ART (p<0.001). After 3, 6 and 9 months of ART adenosine deaminase activity decreases as the CD4 count increases. Elevated serum adenosine deaminase activity in HIV patients is an indicator of T-cell activation. With antiretroviral therapy there is reduction in viral load and T-cell activation, which may explain the gradual decrease in ADA activity. Conclusion: Estimation of serum ADA activity is a simple, rapid and inexpensive test. In this study ADA activity decreased gradually with ART. Thus the study concludes that serum ADA activity may be used as a prognostic marker to monitor response to antiretroviral therapy in HIV patients in limited resource and high incidence areas. [ABSTRACT FROM AUTHOR]

The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (α -methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with α -methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, α-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model. [ABSTRACT FROM AUTHOR]

Endothelin-2 [ET-2; also known as vasoactive intestinal contractor (VIC), in rodents] differs from endothelin-1 (ET-1) by only two amino acids, and unlike the third isoform, endothelin-3 (ET-3), it has the same affinity as ET-1 for both ETA and ETB receptors. It is often assumed that ET-2 would mimic the actions of the more abundant ET-1 and current pharmacological interventions used to inhibit the ET system would also block the actions of ET-2. These assumptions have focused research on ET-1 with ET-2 studied in much less detail. Recent research suggests that our understanding of the ET family requires re-evaluation. Although ET-2 is very similar in structure as well as pharmacology to ET-1, and may co-exist in the same tissue compartments, there is converging evidence for an important and distinct ET-2 pathway. Specifically is has been demonstrated that ET-2 has a key role in ovarian physiology, with ET-2-mediated contraction proposed as a final signal facilitating ovulation. Furthermore, ET-2 may also have a pathophysiological role in heart failure, immunology and cancer. Comparison of ET-2 versus ET-1 mRNA expression suggests this may be accomplished at the level of gene expression but differences may also exist in peptide synthesis by enzymes such as endothelin converting enzymes (ECEs) and chymase, which may allow the two pathways to be distinguished pharmacologically and become separate drug targets. LINKED ARTICLES This article is part of a themed section on Endothelin. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.168.issue-1 [ABSTRACT FROM AUTHOR]

The interaction of heterocyclic thiones/thiosemicarbazones with metals has been the subject of several investigations as these ligands contain chemically active groups,-N(H)-C(=S)-↔ -N=C(-SH)-,and are useful model compounds for sulphur-containing analogues of purine and pyrimidine bases. Heterocylic-2-thiones bind to metals in several ways and lead to the formation of monomeric or polymeric complexes. For example, the simplest prototype of heterocylic-2-thiones, namely, pyridine-2-thione has several ways of binding, notably, terminal S-bonding and S-bridging (in neutral form), while in anionic form the modes are terminal S-bonding, S-bridging, N,S-chelation, N,S-bridging, N,S-chelation-cum-S-bridging and N,S-bridging-cum-S-bridging. Similarly, thiosemicarbazones bind to metals as S-bonded unidentates or N,S-chelates. In this paper, the chemistry of pyridine-2-thione, its N-oxide, 2-(benzylthio)pyridine-1-oxide thione with metals like iron(II), ruthenium(II), nickel(II), palladium(II), platinum(II), copper(I), copper(II), silver(I) and mercury(II) is briefly described. As regards thiosemicarbazones, focus is only on two compounds, namely organomercury(II) and organothallium(III). A variety of new molecules, well characterised by NMR and X-ray crystallography, is introduced. [ABSTRACT FROM AUTHOR]

The evolution of acute lymphoblastic leukemia from a myelodysplastic syndrome is a very uncommon event. We describe a 46-year-old man in whom refractory anemia with excess blasts (RAEB) evolved to a pre-B acute lymphocytic leukemia. Trisomy 8 was one of the cytogenetic abnormalities in the dysplastic clone and was detected in both peripheral blood and bone marrow smears of interphase cells by the fluorescence in situ hybridization (FISH) technique. Using a chromosome 8 centromeric specific DNA probe we identified the trisomy 8 to be present in lymphoblasts, erythroid precursors, myeloblasts, promyelocytes, myelocytes, metamyelocytes, granulocytes, and monocytes. Our case supports the hypothesis that in MDS the pluripotent precursor cell is affected, and we examine the potential role of FISH for the study and follow-up of some hematological diseases. [ABSTRACT FROM AUTHOR]

All beta-adrenoceptor blocking drugs that have been described share the common property of being competitive inhibitors. They differ in their associated properties, the presence or absence of cardioselectivity, membrane stabilizing activity, and partial agonist activity. Recently some beta-adrenoceptor blocking drugs have been reported which also possess alpha-adrenoceptor blocking activity. The associated properties have been used as a basis for classifying beta-adrenoceptor blocking drugs (Fitzgerald, 1969, 1972). The presence or absence of cardioselectivity is most useful for dividing beta-adrenoceptor blocking drugs. The non-selective drugs (Division I) can be further divided according to the presence or absence of intrinsic sympathomimetic activity (ISA) and membrane stabilizing activity (Fitzgerald's groups I-IV). Group I possess both membrane activity and ISA, e.g. alprenolol, oxprenolol, group II just membrane action, e.g. propanolol, group III ISA but no membrane action, e.g. pindolol. Fitzgerald placed pindolol in group I but should be placed in group III as it possesses a high degree of beta-adrenoceptor blocking potency in relation to its membrane activity (Prichard, 1974). Finally drugs in group IV have neither ISA nor membrane action, e.g. sotalol, timolol. The cardioselective drugs (Division II) can be similarly sub-divided into groups I-IV according to the presence or absence of ISA or membrane action (Fitzgerald grouped all these together as group V). Lastly there are new beta-adrenergic receptor blocking drugs which in addition have alpha- adrenergic receptor blocking properties (Division III). [ABSTRACT FROM AUTHOR]

The potential interactions between H2-receptor antagonists, cimetidine and ranitidine, and glibenclamide were studied in 15 non-smoking male volunteers. The study consisted of six treatment phases. Treatment A (3 h oral glucose tolerance test) consisted of 75 g dextrose in 300 ml carbonated water. Treatment B consisted of one 5 mg tablet of glibenclamide in addition to a glucose tolerance test. Treatment C, cimetidine 300 mg orally four times daily for 4 days and Treatment D, ranitidine 150 mg orally twice daily for 4 days were administered in a randomized, crossover fashion. On day 3 of Treatments C and D, subjects received an oral glucose tolerance test. On day 4 of Treatments C and D, subjects received 5 mg of glibenclamide in addition to cimetidine (Treatment E) or ranitidine (Treatment F) and an oral glucose tolerance test. Compared with the control treatment, cimetidine increased the glibenclamide AUC (973 vs 710 ng ml-1 h), but during ranitidine dosing glibenclamide AUC (726 ng ml-1 h) was not significantly different from the control. Apparent oral glibenclamide clearance decreased from 8.25 l h-1 under the control treatment to 6.0 l h-1 following cimetidine but was unchanged during ranitidine (7.97 l h-1). Plasma glucose concentrations were unexpectedly higher when glibenclamide was administered with cimetidine or ranitidine (glucose AUC 237 mg dl-1 h, 228 mg dl-1 h) when compared with glibenclamide administered alone (195 mg dl-1 h, P less than 0.0001). Plasma insulin concentrations were significantly elevated when H2-receptor antagonists and glibenclamide were administered concurrently.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]