Syntheses and evaluation of multicaulin and miltirone-like compounds as antituberculosis agents

Four multicaulin and miltirone-like phenanthrene derivatives were synthesised and evaluated as antituberculosis agents. The crucial step of the synthesis was Pschorr coupling of 4-(3-isopropyl-4-methoxyphenyl)-2-(2-aminophenyl)ethane (13) to give 2-isopropyl-3-methoxy-9,10-dihydrophenanthrene (9) and 4-isopropyl-3-methoxy-9,10-dihydrophenanthrene (9a). Compound 9 was converted to multicaulin and miltirone-like phenanthrene derivatives by further reactions. The best antituberculosis activity was exhibited by 2-isopropylphenanthrene-3-ol (11).     

An Evaluation of Risk Factors in Pregnant Women with <Emphasis Type="Italic">Candida</Emphasis> Vaginitis and the Diagnostic Value of Simultaneous Vaginal and Rectal Sampling

In this study, we investigated the epidemiological characteristics of VVC among pregnant women. We conducted a prospective survey among 372 pregnant women to investigate the prevalence, clinical forms, etiological agents, and predisposing factors of VVC. In addition, we determined the relationship between vaginal and rectal flora by simultaneously obtaining one high vaginal swab and one rectal swab from each patient using sterile cotton-tipped swabs. Furthermore, we compared the recovery and identification performances of chromID Candida agar to Sabouraud dextrose agar with gentamicin and chloramphenicol. Clinically and mycologically confirmed cases of VVC were detected in 139 (37.4%) and vaginal colonization described in 42 (11.3%) of 372 pregnant women. Rectal cultures were also positive in 98 of the 139 (70.5%) VVC cases. Candida albicans and C. glabrata were identified in vaginal samples in 58.0 versus 19.0% and from rectal samples in 49.0 versus 13.5%, respectively. Increases in gestational week and gravidae were identified to be statistically significant in patients with acute VVC (AVVC) and symptomatic recurrent VVC (RVVC), and asymptomatic RVVC (P = 0.04 and P = 0.03, respectively). In the laboratory diagnosis of VVC, specifically tailored chromogenic media are reliable tools for both the recovery and rapid identification of common Candida spp., particularly C. albicans, as well as for the detection of polyfungal populations in vaginal samples (P > 0.05). In addition, rectal colonization is a common finding in cases of AVVC and symptomatic-RVVC cases and corresponds well with the presence of the same yeast species in the vagina.     

Nucleotide homeostasis and purinergic nociceptive signaling in rat meninges in migraine-like conditions

Extracellular ATP is suspected to contribute to migraine pain but regulatory mechanisms controlling pro-nociceptive purinergic mechanisms in the meninges remain unknown. We studied the peculiarities of metabolic and signaling pathways of ATP and its downstream metabolites in rat meninges and in cultured trigeminal cells exposed to the migraine mediator calcitonin gene-related peptide (CGRP). Under resting conditions, meningeal ATP and ADP remained at low nanomolar levels, whereas extracellular AMP and adenosine concentrations were one-two orders higher. CGRP increased ATP and ADP levels in meninges and trigeminal cultures and reduced adenosine concentration in trigeminal cells. Degradation rates for exogenous nucleotides remained similar in control and CGRP-treated meninges, indicating that CGRP triggers nucleotide release without affecting nucleotide-inactivating pathways. Lead nitrate-based enzyme histochemistry of whole mount meninges revealed the presence of high ATPase, ADPase, and AMPase activities, primarily localized in the medial meningeal artery. ATP and ADP induced large intracellular Ca²⁺ transients both in neurons and in glial cells whereas AMP and adenosine were ineffective. In trigeminal glia, ATP partially operated via P2X7 receptors. ATP, but not other nucleotides, activated nociceptive spikes in meningeal trigeminal nerve fibers providing a rationale for high degradation rate of pro-nociceptive ATP. Pro-nociceptive effect of ATP in meningeal nerves was reproduced by α,β-meATP operating via P2X3 receptors. Collectively, extracellular ATP, which level is controlled by CGRP, can persistently activate trigeminal nerves in meninges which considered as the origin site of migraine headache. These data are consistent with the purinergic hypothesis of migraine pain and suggest new targets against trigeminal pain.     

Analysis of zinc and magnesium levels in pinealectomized chicks

Melatonin is the main product of the pineal gland, and trace metals play a critical role in growth and development. The purpose of this study was to assess the serum zinc (Zn) and magnesium (Mg) levels in pinealec-tomized chicks and their possible interactions with the development of spinal deformity. Chicks were divided into two equal groups: unoperated controls (group M) and pinealectomized chicks (group N). Pinealectomies were performed at the age of 3 d. After 8 wk, serum Zn and Mg levels of 10 animals from each group were measured by spectrophotometric assay. The results of analyses were compared using the Mann-Whitney U-test. The correlation between serum Zn and Mg levels were assessed by Spearman's correlation. In this study, it was obvious that the serum Zn levels in group N were significantly lower than those in group M (2.8±0.10 vs 4.2±0.14 ppm; p<0.0005). In contrast, Mg levels in group N was high compared with the values in group M, although there was no significant difference (17.8±0.69 vs 15.7±0.85 ppm; p>0.05). In pinealectomized animals, serum Zn levels declined significantly while serum Mg levels increased, albeit insignificantly. Thus, there was a moderately positive but not statistically significant correlation between Mg and Zn levels in unoperated controls (r=0.273, p>0.05), whereas there was a negative but not statistically significant correlation between Zn and Mg levels in pinealectomized chicks (r=−0.115, p>0.05). In addition, the serum Mg to serum Zn ratio was significantly higher in group N than in the group M control (6.39±0.32 vs 3.75±0.22, respectively; p<0.001). From the results of the current study, it is clear that surgical pinealectomy in newly hatched Hybro Broiler chicks has a significant effect on serum Zn level. However, the serum Mg did not change significantly. Because serum Mg is not a good indicator of Mg status in chicks, it is speculated that other tissues, such as muscle or spine, might productively be explored as a more sensitive Mg biomarker for this model. The present study provides experimental evidence that serum trace metal levels might be affected in pinealectomized animals because of the lack of its main neurohormone melatonin.     

Modeling chlorophenols degradation in sequencing batch reactors with instantaneous feed-effect of 2,4-DCP presence on 4-CP degradation kinetics

Two instantaneously fed sequencing batch reactors (SBRs), one receiving 4-chlorophenol (4-CP) (SBR4) only and one receiving mixture of 4-CP and 2,4-dichlorophenol (2,4-DCP) (SBRM), were operated with increasing chlorophenols concentrations in the feed. Complete degradation of chlorophenols and high-Chemical oxygen demand (COD) removal efficiencies were observed throughout the reactors operation. Only a fraction of biomass (competent biomass) was thought to be responsible for the degradation of chlorophenols due to required unique metabolic pathways. Haldane model developed based on competent biomass concentration fitted reasonably well to the experimental data at different feed chlorophenols concentrations. The presence of 2,4-DCP competitively inhibited 4-CP degradation and its degradation began only after complete removal of 2,4-DCP. Based on the experimental results, the 4-CP degrader’s fraction in SBRM was estimated to be higher than that in SBR4 since 2,4-DCP degraders were also capable of degrading 4-CP due to similarity in the degradation pathways of both compounds.     

Kinetics of iron oxidation by Leptospirillum ferriphilum dominated culture at pH below one

The kinetics of ferrous iron oxidation by Leptospirillum ferriphilum (L. ferriphilum) dominated culture was studied in the concentration range of 0.1-20 g Fe(2+)/L and the effect of ferric iron (0-60 g Fe(3+)/L) on Fe(2+) oxidation was investigated at pH below one. Denaturing gradient gel electrophoresis of PCR amplified 16S rRNA genes followed by partial sequencing confirmed that the bacterial community was dominated by L. ferriphilum. In batch assays, Fe(2+) oxidation started without lag phase and the oxidation was completed within 1 to 60 h depending on the initial Fe(2+) concentration. The specific Fe(2+) oxidation rates increased up to around 4 g/L and started to decrease at above 4 g/L. This implies substrate inhibition of Fe(2+) oxidation at higher concentrations. Haldane equation fitted the experimental data reasonably well (R(2) = 0.90). The maximum specific oxidation rate (q(m)) was 2.4 mg/mg VS . h, and the values of the half saturation (K(s)) and self inhibition constants (K(i)) were 413 and 8,650 mg/L, respectively. Fe(2+) oxidation was competitively inhibited by Fe(3+) and the competitive inhibition constant (K(ii)) was 830 mg/L. The time required to reach threshold Fe(2+) concentration was around 1 day and 2.3 days with initial Fe(3+) concentration of 5 and 60 g/L, respectively. The threshold Fe(2+) concentration, below which no further Fe(2+) oxidation occurred, linearly increased with increasing initial Fe(2+) and Fe(3+) concentrations. Fe(2+) oxidation proceeds by L. ferriphilum dominated culture at pH below 1 even in the presence of 60 g Fe(3+)/L. This indicates potential of using and biologically regenerating concentrated Fe(3+) sulfate solutions required, for example, in indirect tank leaching of ore concentrates.     

The relationship of the ESR1 gene polymorphisms with the presence of coronary artery disease determined by coronary angiography

Effects of estrogen on the cardiovascular system, mediated mainly by estrogen receptor type alpha (ER alpha), have been well-defined and specific polymorphisms in the ER alpha gene (ESR1) have been associated with several coronary heart diseases including coronary artery disease (CAD) in studies covering different populations. In the present study, we aimed to investigate whether there is an association between two of the known polymorphisms in the ESR1, named c.454-397T>C and c.454-351A>G, and CAD in a Turkish population. One hundred sixty eight patients with CAD and 99 patients without CAD were included in the study. The ESR1 c.454-397T>C and c.454-351A>G polymorphisms were studied by the conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. While no association was found between the c.454-351A>G polymorphism and CAD, the c.454-397T>C genotype distributions were statistically significant independent of known risk factors between CAD-positive (CAD+) and CAD-negative (CAD-) groups (p = 0.001). TT genotype was more frequent in CAD- group than in CAD+ group, 22.2% and 4.8%, respectively. CC genotype was associated with increased risk of CAD (p = 0.001) compared to the TT genotype. When comparing the distribution of CC + TC genotypes to that of TT genotype in CAD+ and CAD- groups, the frequency of CC + TC genotypes showed a significant increase independent of known CAD risk factors in CAD+ subjects (p = 0.001). As a conclusion, a statistically significant relationship between the ESR1 c.454-397T>C polymorphism and CAD were found independent of known CAD risk factors in a Turkish population.