Successful treatment of lupoid cutaneous leishmaniasis with glucantime and topical trichloroacetic acid (a case report)

Lupoid leishmaniasis is a unique form of cutaneous leishmaniasis characterized by unusual clinical features and a chronic relapsing course, mostly caused by infection with Leishmania tropica. In this clinical form, 1-2 yr after healing of the acute lesion, new papules and nodules appear at the margin of the remaining scar. Herein, we describe a case of this clinical form that was resistant to 2 courses of treatments: systemic glucantime and then a combination therapy with allopurinol and systemic glucantime. However, marked improvement was seen after a combination therapy with topical trichloroacetic acid solution (50%) and systemic glucantime, and there were no signs of recurrence after 1 yr of follow-up.     

Origin and history of the IVS-I-110 and codon 39 beta-thalassemia mutations in the Lebanese population

Using restriction fragment length polymorphisms (RFLPs) and sequence haplotype analysis, we studied the chromosomal background of the beta-globin gene in 31 unrelated Lebanese IVS-I-110 or codon 39 (Cd39) subjects, and five normal betaAbeta/A individuals. Our results are compared with those from similar studies in other parts of the Mediterranean in an attempt to provide insights into historical patterns of selection and disease. The great majority of the Lebanese chromosomes with the IVS-I-110 mutation are associated with the RFLP haplotype I and sequence haplotype HT1, which is probably the ancestral structure on which the mutation first emerged. The remainder of the IVS-I-110 alleles are linked to the 5'-subhaplotype 12 RFLP haplotype and/or HTR sequence haplotype. In contrast, in Turkey, IVS-I-110 is associated with six distinct sequence haplotypes and four distinct RFLP haplotypes, suggesting that the mutation probably emerged there. The diversity of sequence haplotypes described in Turkey was probably generated through recombination or gene conversion events with the most frequent betaA autochthonous structures. Our data on Lebanese betaA chromosomes and Algerian betaA chromosomes, along with previously described Turkish betaA chromosomes, strengthen this hypothesis. Following its emergence in Turkey, the IVS-1-110 mutation was probably introduced to Lebanon later, by migration or settlements. Cd39 demonstrates a remarkable level of sequence and RFLP haplotype heterogeneity in Algeria, in contrast to its relative homogeneity in Turkish samples. However, its rarity in the Near East, and more specifically in Lebanon, does not allow us to draw any conclusions concerning its origin and gene flow.     

Potential of Indigenous Plant Species for the Phytoremediation of Arsenic Contaminated Land in Kurdistan (Iran)

To evaluate the potential of the indigenous plant species for Arsenic (As) phytoremediation, a total of 138 plant samples and 138 soil samples from rooting zones were collected from two As-contaminated areas in Kurdistan, western Iran. The areas were the Sari Gunay Gold Mine (SG) and Ali Abad Village (AA). The soil of both areas naturally contains As, with mining activities at SG. Soil and plant samples were collected at five sites in the SG (SG1 to SG5) and at two sites in the AA (AA1 and AA2). Soil samples were analyzed for total and water-soluble As concentration, as well as for the main soil physical and chemical properties such as electrical conductivity (Ec), pH, organic carbon (C_org.), available phosphorus (P_ava.), and soil texture. Plant samples were analyzed for As concentration in their shoots and roots.

The average total and water–soluble As concentrations in soil were 751.6 and 6.2 ppm at SG and 920.8 and 8.0 ppm at AA, respectively. The highest root and shoot As concentration was found in Juncus inflexus (751.5 ppm) at AA2 and in Astragalus gossypinus (158.7 ppm) at AA1, respectively. With regard to phytoremediation strategies, Acantholimon brachystachyum, Astragalus gossypinus, Stipa barbata, and Ephedra major with a high translocation factor (TF) can be potentially used for As phytoextraction. However, Juncus inflexus, Phragmites australis, Bromus tomentellus, and Elymus sp., which show high bioconcentration factor (BCF) and low TF, are suggested as good candidates for As phytostabilization. In general, the TF values of terrestrial plants were higher than those of amphibious plants; meanwhile, BCF values showed the opposite behavior.     

Prolactin's mediative role in male parenting in parentally experienced marmosets (Callithrix jacchus)

Prolactin has been implicated in promoting paternal care behaviors but little evidence of causality has been found to date except for birds and fish. This study was designed to examine the possible causal relationships between prolactin and male parenting behaviors, reproductive hormones, and physical changes in cooperatively breeding common marmosets, Callithrix jacchus. Fifteen parentally experienced fathers were studied over three consecutive infant care periods during two weeks prior and three weeks following their mates' parturition under three-treatment conditions: normal control pregnancy, decreased prolactin and elevated prolactin. The treatments significantly altered the serum prolactin levels in the fathers. Using three methods of determining a father's level of parental care: infant carrying, family effort and responsiveness to infant stimulus tests, we found that only the male response to infant stimuli was altered by the hormone treatments. Lowering prolactin significantly reduced male responsiveness to infant stimuli but elevating prolactin showed the same effect. Hormonal sampling indicated that testosterone levels showed an inverse relationship to prolactin levels during a normal peripartum period and prolactin treatment reduced this relationship. Prepartum estradiol levels were significantly elevated during the lowered prolactin treatment and estradiol was significantly lowered postpartum with the elevated prolactin treatment. Father's weight decreased significantly by the third week of infant care during the normal treatment. Males in the elevated prolactin treatment lost little or no weight from prepartum while in the lowered prolactin treatment showed the most weight loss. The present findings did not distinguish a direct causal relationship of prolactin on behavior in experienced fathers but did find an interaction with other hormones and weight gain.     

Adenylyl cyclase P-site ligands accelerate differentiation in Ob1771 preadipocytes

Differentiation of Ob1771 preadipocytes to adipocytes wascharacterized by morphological changes and elevated expression of thespecific marker enzyme, glycerol-3-phosphate dehydrogenase. Adifferentiation response substantially more complete and rapid thanthat obtained with insulin and 3,5,3'-triiodothyronine was observed with established inhibitors of adenylyl cyclases:2',5'-dideoxyadenosine (2',5'-dd-Ado),9-(cyclopentyl)adenine (9-CP-Ade), and 9-(arabinofuranosyl)adenine (9-Ara-Ade), coincident with decreased cellular cAMP levels. These ligands inhibit adenylyl cyclases noncompetitively, via a domain referred to as the P-site because of its requirement for an intact purine moiety. Differentiation was not induced by inosine, a nucleoside known not to act at the P-site, or byN⁶-(2-phenylisopropyl)adenosineor 1,3-diethyl-8-phenylxanthine, agonist and antagonist, respectively,for adenosine A₁ receptors. Alsoineffective were IBMX or forskolin, agents that can raise intracellularcAMP levels. Potency of the differentiation response followed the order2',5'-dd-Ado (1-20 µM) > 9-CP-Ade (10-100µM) = 9-Ara-Ade (10-100 µM) >> inosine, consistent withtheir potencies to inhibit adenylyl cyclases. The data suggest thatinhibition of adenylyl cyclase via the P-site and the consequentreduction in cell cAMP levels facilitate the induction ofdifferentiation in Ob1771 cells. The findings raise the questionwhether the known endogenous P-site ligands participate in thedifferentiation response induced by hormones.     

Potassium channels in cell cycle and cell proliferation

Normal cell-cycle progression is a crucial task for every multicellular organism, as it determines body size and shape, tissue renewal and senescence, and is also crucial for reproduction. On the other hand, dysregulation of the cell-cycle progression leading to uncontrolled cell proliferation is the hallmark of cancer. Therefore, it is not surprising that it is a tightly regulated process, with multifaceted and very complex control mechanisms. It is now well established that one of those mechanisms relies on ion channels, and in many cases specifically on potassium channels. Here, we summarize the possible mechanisms underlying the importance of potassium channels in cell-cycle control and briefly review some of the identified channels that illustrate the multiple ways in which this group of proteins can influence cell proliferation and modulate cell-cycle progression.     

Dynamic Regulation of α-Actinin’s Calponin Homology Domains on F-Actin

α-Actinin is an essential actin cross-linker involved in cytoskeletal organization and dynamics. The molecular conformation of α-actinin’s actin-binding domain (ABD) regulates its association with actin and thus mutations in this domain can lead to severe pathogenic conditions. A point mutation at lysine 255 in human α-actinin-4 to glutamate increases the binding affinity resulting in stiffer cytoskeletal structures. The role of different ABD conformations and the effect of K255E mutation on ABD conformations remain elusive. To evaluate the impact of K255E mutation on ABD binding to actin we use all-atom molecular dynamics and free energy calculation methods and study the molecular mechanism of actin association in both wild-type α-actinin and in the K225E mutant. Our models illustrate that the strength of actin association is indeed sensitive to the ABD conformation, predict the effect of K255E mutation—based on simulations with the K237E mutant chicken α-actinin—and evaluate the mechanism of α-actinin binding to actin. Furthermore, our simulations showed that the calmodulin domain binding to the linker region was important for regulating the distance between actin and ABD. Our results provide valuable insights into the molecular details of this critical cellular phenomenon and further contribute to an understanding of cytoskeletal dynamics in health and disease.     

Association study of rs10768683 and rs968857 polymorphisms with transfusion-dependent thalassemia (TDT) in a southern Iranian population

Previous studies reported that detection of polymorphisms inherited through paternal model could be potential markers for the Non-Invasive Prenatal Diagnosis (NIPD) of β-thalassemia. The aim of the current study was to find out the associations of rs10768683 and rs968857 with transfusion-dependent thalassemia (TDT) in a southern Iranian population. A total of 175 subjects were investigated, divided into patients with TDT as case group (n?=?75) and healthy people as control group (n?=?100). Genomic DNAs were extracted from peripheral blood using salting out procedure. Genotyping rs10768683 and rs968857 was carried out by ARMS-PCR, then statistical analyses were assessed using SPSS, and Medcalc ver. 18 software. Data showed that rs10768683 was statistically significant in co-dominant model of inheritance (P?=?0.025, OR?=?2.11 [1.08-4.15]) and genotype frequencies of CG among controls and cases were 0.68 and 0.80, respectively. However, according to genotype frequencies, there was no association between rs968857 and TDT among cases and healthy controls in any models of inheritance. In conclusion, the present study showed the association of rs10768683 with major β-thalassemia through ARMS-PCR technique.