Water proton relaxation rate enhancements and association constants for Mn(II) to serum proteins determined by NMR T1 measurements

The water proton relaxation rate enhancement of Mn(II) bound to bovine serum albumin (BSA) and the association constant for manganese to BSA have already been determined, but such determinations have not been done for human serum albumin (HSA) and other human serum proteins and also for human serum. In this work, NMR T1 values in aqueous solutions of serum proteins and serum were measured versus increasing concentration of Mn(II). Proton relaxation rate enhancements (epsilon*) caused by different manganese concentrations were determined for each solution and 1/epsilon* was fitted against concentrations of Mn(II). Proton relaxation rate enhancements (epsilonb) of Mn(II) bound to albumin, gamma-globulin, (alpha+beta)-globulins and serum were found to be 13.69, 3.09, 8.62, and 10.87, respectively. Free and bound manganese fractions, resulted from each addition of Mn(II) to the sample, were determined by using corresponding (epsilon*) and the epsilonb values. Association constants for Mn(II) to HSA and gamma-globulin were calculated as 1.84 x 10(4) M(-1) and 2.35 x 10(4) M(-1), respectively. Present data suggest that the proton relaxation rate enhancement of Mn(II) in serum is caused by Mn(II) bound to various serum constituents. Data also suggest that association constants for Mn(II) to gamma-globulin are nearly the same as that to HSA.     

Levels of cytokines (IL-1beta, IL-2, IL-6, IL-8, TNF-alpha) and trace elements (Zn, Cu) in breast milk from mothers of preterm and term infants

It has been well documented that human milk contains several immunomodulator components which are important during infant period when the newborn's immune system is still under development. In this study, we aim at examining levels of cytokines, zinc (Zn), and copper (Cu) in milk from mothers of premature and mature infants, and comparing changes during lactation periods consequently. Milk was collected from total of 40 mothers (group M: mothers of mature infants, n = 20; group PM: mothers of premature infants, n = 20) from four lactation stages: colostrum (0-7 days), transitional (7-14 days), mature milk (21 days), and mature milk (2nd month). Levels of cytokines (interleukin [IL]-lbeta, IL-2, IL-6, IL-8, tumor necrosis factor-alpha [TNF-alpha]) were determined by chemiluminesence method, whereas atomic absorption spectrophotometer was used for the determination of Zn and Cu levels. Cytokine levels were determined to be high in colostrum and transient milk from mothers of full-term infants, whereas their levels were reduced drastically in the 21st day and the 2nd month milk (P < .01, P < .001). Similar trends were observed in milk from mothers of premature infants, but cytokine levels were significantly lower in colostrum compared to colostrum from mothers of mature infants (P < .01). The differences in cytokine levels were continuous in transient milk (P < .05) and mature milk (21 days) (P < .05), whereas there was no statistically significant differences between milk from both groups of mothers in the 2nd month (P > .05). Zn levels in milk from mothers of premature infants were significantly lower compared to the ones from mothers of mature infants (P < .01) and these differences continued through the 2nd month. Although Cu levels were lower in milk from mothers of premature infants, there was no statistically significant difference except colostrum (P > .05). Our results clearly demonstrate that the level of immunomodulating agents such as cytokines and trace elements in milk from mothers of premature infants is less than the level of the same agents in milk from mothers of full-term infants. Although there are commercially available products for infant feeding, human milk is still the best natural nutrient for newborns. Therefore, when premature infants are breastfed, necessary precautions such as supplemantary diets must be considered for possible infections and risks related with immune system deficiency.     

Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration

Background

The aim of the study was to assess the chronic effects of combined phosphodiesterase 3/4 inhibitor tolafentrine, administered by inhalation, during monocrotaline-induced pulmonary arterial hypertension (PAH) in rats.

Methods

CD rats were given a single subcutaneous injection of monocrotaline to induce PAH. Four weeks after, rats were subjected to inhalation of tolafentrine or sham nebulization in an unrestrained, whole body aerosol exposure system. In these animals (i) the acute pulmonary vasodilatory efficacy of inhaled tolafentrine (ii) the anti-remodeling effect of long-term inhalation of tolafentrine (iii) the effects of tolafentrine on the expression profile of 96 genes encoding cell adhesion and extracellular matrix regulation were examined. In addition, the inhibitory effect of tolafentrine on ex vivo isolated pulmonary artery SMC cell migration was also investigated.

Results

Monocrotaline injection provoked severe PAH (right ventricular systolic pressure increased from 25.9 ± 4.0 to 68.9 ± 3.2 after 4 weeks and 74.9 ± 5.1 mmHg after 6 weeks), cardiac output depression and right heart hypertrophy. The media thickness of the pulmonary arteries and the proportion of muscularization of small precapillary resistance vessels increased dramatically, and the migratory response of ex-vivo isolated pulmonary artery smooth muscle cells (PASMC) was increased. Micro-arrays and subsequent confirmation with real time PCR demonstrated upregulation of several extracellular matrix regulation and adhesion genes, such as matrixmetalloproteases (MMP) 2, 8, 9, 10, 11, 12, 20, Icam, Itgax, Plat and serpinb2. When chronically nebulized from day 28 to 42 (12 daily aerosol maneuvers), after full establishment of severe pulmonary hypertension, tolafentrine reversed about 60% of all hemodynamic abnormalities, right heart hypertrophy and monocrotaline-induced structural lung vascular changes, including the proportion of pulmonary artery muscularization. The upregulation of extracellular matrix regulation and adhesion genes was reduced by nearly 80% by inhalation of the tolafentrine. When assessed in vitro, tolafentrine blocked the enhanced PASMC migratory response.

Conclusion

In conclusion, we demonstrate for the first time that inhalation of combined PDE3/4 inhibitor reverses pulmonary hypertension fully developed in response to monocrotaline in rats. This "reverse-remodeling" effect includes structural changes in the lung vascular wall and key molecular pathways of matrix regulation, concomitant with 60% normalization of hemodynamics.     

Prenatal diagnosis of mosaicism identified in amniotic fluid cell cultures

Chromosomal mosaicism in prenatal diagnosis is an important problem to be solved immediately and the probable phenotypic reflections should be explained to the family. We report two numerical and two structural mosaicisms detected in amniocyte cultures. The first fetus had a 47,XY,+mar[10]/46,XY[10] karyotype. The marker chromosome was shown to be derived from chromosome 15 by FISH method. The newborn had intrauterine growth retardation and cerebral thrombosis and died at the 29th day of age. The second fetus had a 45,X[4]/46,XX[26] karyotype. The parents refused cordocentesis and decided to terminate pregnancy in the 21st week. The third case, presented with bilateral large choroid plexus cysts, had a 46,XX, dup(1)(q22-q32)[9]/46,XX[21] karyotype. The parents' karyotypes were normal and the pregnancy was aborted in the 23rd week of gestation. The second structural abnormality was reported as 46,XX,t(6;11)(q23; p13)[3]/46,XX[20]. The mosaicism was detected in only one flask. The parents decided to continue pregnancy and cordocentesis could not be performed due to the fetal and placental position. The baby was born at term. Peripheral blood lymphocyte culture resulted in a 46,XX normal karyotype. Information and risks were explained to all families during genetic counseling. Mosaicism in prenatal diagnosis needs both detailed examination and follow up, since clinical findings depend on the type of abnormality.     

Squatting facet: a case study Dilkaya and Van-Kalesi populations in eastern Turkey

Anomalies of the skeleton provide information on living conditions, cultural structure and health problems in ancient societies. Squatting facet is a kind of anomaly that forms on the surfaces where the tibia and talus articulate is the squatting facet states the daily activities and living style of the society. The aim of this study is to learn the daily activities of the medieval societies in the Van region through studying of squatting facets. In this study, adult skeletons from Dilkaya and Van Kalesi-Eski Van Sehri societies dating to the Medieval Age were investigated (65 tibia and 82 tali from Dilkaya, 61 tibia and 52 tali from Van Kalesi-Eski Van Sehri). The lateral squatting facet had high ratios in both societies. The tibia lateral squatting facet found on females and males of Dilkaya was 97.2% and 96.9%, respectively, and on females and males of Van kalesi Eski Van Sehri was 87.5% and 89.2%, respectively. The talus lateral squatting facet found on females and males of Dilkaya was 72.1% and 51.3%, respectively, and on females and males of Van kalesi Eski Van Sehri was 91.2% and 83.7%, respectively. The results provide an opportunity to study the relationship between past and modern population, and also describe the daily activity of life and cultural structure.     

Fryns syndrome with atypical findings--with large midline cleft on forehead but normal cranial MRI findings

We report a newborn with Fryns syndrome and atypical findings like a large midline cleft on forehead. Abnormal findings included congenital left diaphragmatic hernia, prominent forehead, hypertelorism, broad nasal bridge, anteverted nostrils, cleft palate, low set ears, tapered fingers, macrocephaly, congenital heart defect, midline defects and renal anomalies. This is the first case that has a midline cleft on forehead with normal cranial MRI findings.     

Sonochemical syntheses of strawberry-like nano-structure mixed-ligand lead(II) coordination polymer: Thermal, structural and X-ray powder diffraction studies

Nano-structure of a new Pb(II) two-dimensional coordination polymer, {[Pb(2-pyc)(N₃)(H₂O)]_n (1), 2-Hpyc = 2-pyridinecarboxylic acid} was synthesized by a sonochemical method. The new nano-structure was characterized by scanning electron microscopy, X-ray powder diffraction, IR spectroscopy and elemental analyses. Compound 1 was structurally characterized by single crystal X-ray diffraction and consists of two-dimensional polymeric units. The thermal stability of compound 1 was studied by thermal gravimetric and differential thermal analyses and compared. PbO nano-powder was obtained by calcination of the nano-structure of compound 1 at 400 °C. This study demonstrates the coordination polymers may be suitable precursors for the preparation of nano-scale materials and dependent on their packing they may produce different and interesting morphologies.     

Antimicrobial activity of extracts of chemical races of the lichen Pseudevernia furfuracea and their physodic acid, chloroatranorin, atranorin, and olivetoric acid constituents

The antimicrobial activity and the MIC values of the ethanol, chloroform, diethyl ether, and acetone extracts of the chemical races of Pseudevernia furfuracea (var. furfuracea and var. ceratea) and their physodic acid, chloroatranorin, atranorin, and olivetoric acid constituents have been investigated against some microorganisms. Nearly all extracts of both chemical races showed antimicrobial activity against Aeromonas hydrophila, Bacillus cereus, Bacillus subtilis, Listeria monocytogenes, Proteus vulgaris, Staphylococcus aureus, Streptococcus faecalis, Yersinia enterocolitica, Candida albicans, Candida glabrata, Alternaria alternata, Ascochyta rabiei, Aspergillus niger, Fusarium culmorum, Fusarium moniliforme, Fusarium oxysporum, Fusarium solani, and Penicillium notatum. There was no antimicrobial activity of the extracts against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas syringae, Salmonella typhimurium, Alternaria citri, Alternaria tenuissima, and Gaeumannomyces graminis. Chloroatranorin and olivetoric acid were active against the same microorganisms with few exceptions. Physodic acid was active against about the same bacteria and yeasts and inactive against all of the filamentous fungi tested. Also no activity of atranorin against the filamentous fungi was observed.     

Protective effect of aminoguanidine against oxidative stress in an experimental peritoneal adhesion model in rats

Postoperative intraperitoneal adhesion formation is a major cause of intestinal obstruction, pain and infertility. This experimental study was designed to evaluate the degree of adhesion formation and peritoneal tissue levels of malondialdehyde (MDA), reduced glutathione (GSH) and total nitrite and nitrate (NO) and the effect of aminoguanidine (AG) on these metabolite values after postoperative intraperitoneal adhesion formation in rats. A total of 21 adult male Wistar albino rats were randomly divided into three groups. Control rats were untreated; the AG group received AG 200 mg kg(-1) i.p. for 10 consecutive days intraperitoneally after surgery. The sham group was given 0.9% NaCl. The rats were killed on postoperative day 10. The peritoneal tissues were harvested to determine the tissue levels of MDA, GSH, and NO activity. For light microscopic evaluation, the cecum was removed. Adhesion formation scores in the AG group were significantly lower than those of the control and sham groups (p < 0.017, p < 0.026 respectively). In the AG-treated rats, tissue levels of MDA and NO were significantly lower than in the control group (p < 0.017). The levels of GSH in aminoguanidine-treated rats were significantly higher than those of the control group (p < 0.01). The severity of the inflammation was more prominent in the control group compared with the AG-injected rats. The results demonstrate that in this experimental model, intraperitoneal administration of aminoguanidine decreases the incidence and extent of peritoneal adhesions and causes a decrease in MDA and NO and an increase in GSH values.