Noninvasive determination of local pulse wave velocity and wave intensity: changes with age and gender in the carotid and femoral arteries of healthy human

We recently introduced noninvasive methods to assess local pulse wave velocity (PWV) and wave intensity ((n)dI) in arteries based on measurements of flow velocity (U) and diameter (D). Although the methods were validated in an experimental setting, clinical application remains lacking. The aim of this study was therefore to investigate the effect of age and gender on PWV and (n)dI in the carotid and femoral arteries of an existing population. We measured D and U in the carotid and femoral arteries of 1,774 healthy subjects aged 35-55 yr, a subgroup of the Asklepios population. With the use of the lnDU-loop method, we calculated local PWV, which was used to determine arterial distensibility ((n)Ds). We then used the new algorithm to determine maximum forward and backward wave intensities ((n)dI(+max) and (n)dI(-min), respectively) and the reflection index ((n)RI). On average, PWV was higher, and (n)Ds was lower in the femoral than at the carotid arteries. At the carotid artery, PWV increased with age, but (n)Ds, (n)dI(+max), and (n)dI(-min) decreased; (n)RI did not change with age. At the femoral artery, PWV was higher, and (n)Ds was lower in male, but all parameters did not change significantly with age in both women and men. We conclude that the carotid artery is more affected by the aging process than the femoral artery, even in healthy subjects. The new techniques provide mechanical and hemodynamic parameters, requiring only D and U measurements, both of which can be acquired using ultrasound equipment widely available today, hence their advantage for potential use in the clinical setting.     

Antimycobacterial activity: a facile three-component [3+2]-cycloaddition for the regioselective synthesis of highly functionalised dispiropyrrolidines

A series of twelve dispiropyrrolidines were synthesized using [3+2]-cycloaddition reactions. The synthesized compounds were screened for their antimycobacterial activity against M. tuberculosis H(37)Rv and INH resistant M. tuberculosis strains using agar dilution method, four of them showed good activity with MIC of less than 1 μM. Compound 4'-[5-(4-fluorophenyl)pyridin-3-yl]-1'-methyldispiro[indan-2,2' pyrrolidine-3',2″-indan]-1,3,1″-trione (4b) was found to be the most active with MIC of 0.1215 and 5.121 μM, respectively.     

Synthesis, anticancer activity and apoptosis inducing ability of bisindole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates

A series of bisindole-pyrrolobenzodiazepine conjugates (5a-f) linked through different alkane spacers was prepared and evaluated for their anticancer activity. All compounds exhibited significant anticancer potency and the most potent compounds 5b and 5e were taken up for detailed studies on MCF-7 cell line. Cell cycle effects were examined apart from investigating the inhibition of tubulin polymerization for compounds 2a, 2b, 5b and 5e at 2μM. FACS analysis showed that at higher concentrations (4 and 8μM) there was an increase of sub-G1 phase cells and decrease of G2/M phase cells, thus indicating that compounds 5b and 5e are effective in causing apoptosis in MCF-7 cells. It was also observed that compounds 5b and 5e showed the down regulation of histone deacetylase protein levels such as HDAC1, 2, 3, 8 and increase in the levels of p21, followed by apoptotic cell death. The apoptotic nature of these compounds was further evidenced by increased expression of cleaved-PARP and active caspase-7 in MCF-7 cells.     

AChE inhibitor: a regio- and stereo-selective 1,3-dipolar cycloaddition for the synthesis of novel substituted 5,6-dimethoxy spiro[5.3']-oxindole-spiro-[6.3″]-2,3-dihydro-1H-inden-1″-one-7-(substituted aryl)-tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole

Pyrrolothiazolyloxindole analogues share vital pharmacological properties, considered useful in Alzheimer's disease (AD). The aim of this study was synthesis and evaluate pyralothiazolyloxindole analogues if possess acetyl cholinesterase (AChE) inhibitory activity. The easily accessible one-pot synthesis of these compounds resulted to be significantly less difficult and expensive than that of donepezil. Several compounds possess anti-cholinesterase activity in the order of micro and sub-micromolar. Particularly, compound was the most potent inhibitors of the series against acetyl cholinesterase enzyme with IC(50) 0.11μmol/L.     

Urbanization and green space dynamics in Greater Dhaka, Bangladesh

Green space is particularly indispensable for proper functioning of the ecosystem in an urban environment. This study was an attempt to dynamically map and monitor green spaces in Greater Dhaka of Bangladesh. Both primary and secondary data were acquired to document the spatial–temporal dynamics of green spaces in the study area. Using a supervised classification algorithm, multi-temporal land use/cover data were extracted from a set of satellite images. A number of spatial metrics were employed to understand the landscape condition in a multi-temporal manner. In addition, 50 key informants along with focus group discussion and observation techniques were used to document existing management aspects of green spaces and their conservation policies. The analysis revealed that green spaces in Greater Dhaka are rapidly disappearing over the course of time even though they provide a number of natural, economic and social benefits. The disappearance of green spaces was primarily attributed to a rapid increase in the urban population, mainly driven by rural–urban migration. As a result, the landscape became highly fragmented and less connected. A substantial reduction of green patches is also leading to deterioration of the ecological condition of the landscape. The drastic reduction of green spaces in Greater Dhaka has been attributed to a lack of policy, low political motivation, and poor management. In order to ensure sustainability of green spaces and proper functioning of the city’s ecosystem, there is an urgent need for strategic green space planning.     

AVPR1A and SLC6A4 polymorphisms in choral singers and non-musicians: a gene association study

Amateur choral singing is a common pastime and worthy of study, possibly conferring benefits to health and social behaviour. Participants might be expected to possess musical ability and share some behavioural characteristics. Polymorphisms in genes concerned with serotonergic neurotransmission are associated with both behaviour and musical aptitude. Those investigated previously include the variable number tandem repeats RS1, RS3 and AVR in the AVPR1A (arginine vasopressin receptor 1a) gene and STin2 in the SLC6A4 (solute carrier family 6 [neurotransmitter transporter, serotonin], member 4) gene, as well as the SLC6A4 promoter region polymorphism, 5-HTTLPR. We conducted a genetic association study on 523 participants to establish whether alleles at these polymorphisms occur more commonly in choral singers than in those not regularly participating in organised musical activity (non-musicians). We also analysed tagging single nucleotide polymorphisms (SNPs) for AVPR1A and SLC6A4 to determine whether other variants in these genes were associated with singer/non-musician status. At the STin2 polymorphism, overall association with singer/non-musician status was evident at P = 0.006. The 9-repeat (P = 0.04) and 12-repeat (P = 0.04) alleles were more common in singers and the 10-repeat allele less so (P = 0.009). Odds ratios were 0.73 (95% CI 0.57-0.94) for the 10-repeat allele and 2.47 (95% CI 0.88-6.94) for the rarer 9-repeat allele. No overall association was detected at P<0.05 between any other polymorphism and singer/non-musician status. Our null findings with respect to RS3, RS1 and AVR, polymorphisms associated with musical ability by other authors, suggest that choir membership may depend partly on factors other than musical ability. In a related musical project involving one participating choir, a new 40-part unaccompanied choral work, "Allele", was composed and broadcast on national radio. In the piece, each singer's part incorporated their personal RS3 genotype.     

Effect of metformin and spironolactone therapy on OGTT in patients with polycystic ovarian syndrome - a retrospective analysis

Background: Metformin (an insulin sensitizer) and spironolactone (an antiandrogen) are both used for treatment of polycystic ovary syndrome. We analyzed the effect of 6 months of therapy with these drugs on body weight and glucose tolerance. Results: This was a retrospective analysis of polycystic ovarian syndrome (PCOS) cases on treatment. There were 88 patients with PCOS-42 were on metformin 1 g daily and 46 were taking spironolactone 50-75 mg daily. 21 of 42 had abnormal glucose tolerance (AGT) in the metformin group and 13 of 46 had AGT in the spironolactone group. Patients on metformin reported a greater reduction in body weight, whereas there was no change in body weight with spironolactone therapy (67.6-63.7 versus 59.6-59.2 kg). There was a significant reduction in the 1 and 2 h glucose and insulin levels with metformin therapy in those with AGT. However, fasting glucose increased in those with normal glucose tolerance. There was no change in either body weight or insulin levels with spironolactone. But, there was a significant reduction in both the 0 and 2 h glucose with spironolactone also in those with AGT. Conclusion: Spironolactone and metformin had similar effect in reducing the glucose levels in PCOS patients with AGT. PCOS patients with normal glucose tolerance had higher fasting plasma glucose at the end of 6 months of metformin therapy inspite of weight reduction.     

Artemether-lumefantrine to treat malaria in pregnancy is associated with reduced placental haemozoin deposition compared to quinine in a randomized controlled trial

ABSTRACT: BACKGROUND: Data on efficacy of artemisinin-based combination therapy (ACT) to treat Plasmodium falciparum during pregnancy in sub-Saharan Africa is scarce. A recent open label, randomized controlled trial in Mbarara, Uganda demonstrated that artemether-lumefantrine (AL) is not inferior to quinine to treat uncomplicated malaria in pregnancy. Haemozoin can persist in the placenta following clearance of parasites, however there is no data whether ACT can influence the amount of haemozoin or the dynamics of haemozoin clearance. METHODS: Women attending antenatal clinics with weekly screening and positive blood smears by microscopy were eligible to participate in the trial and were followed to delivery. Placental haemozoin deposition and inflammation were assessed by histology. To determine whether AL was associated with increased haemozoin clearance, population haemozoin clearance curves were calculated based on the longitudinal data. RESULTS: Of 152 women enrolled in each arm, there were 97 and 98 placental biopsies obtained in the AL and quinine arms, respectively. AL was associated with decreased rates of moderate to high grade haemozoin deposition (13.3% versus 25.8%), which remained significant after correcting for gravidity, time of infection, re-infection, and parasitaemia. The amount of haemozoin proportionately decreased with the duration of time between treatment and delivery and this decline was greater in the AL arm. Haemozoin was not detected in one third of biopsies and the prevalence of inflammation was low, reflecting the efficacy of antenatal care with early detection and prompt treatment of malaria. CONCLUSIONS: Placental haemozoin deposition was decreased in the AL arm demonstrating a relationship between pharmacological properties of drug to treat antenatal malaria and placental pathology at delivery. Histology may be considered an informative outcome for clinical trials to evaluate malaria control in pregnancy. Trial registration REGISTRY: http://clinicaltrials.gov/ct2/show/NCT00495508.     

First molecular epidemiological study of cutaneous leishmaniasis in Libya

Background

Cutaneous leishmaniasis (CL) is a major public health problem in Libya. The objective of this study was to investigate, for the first time, epidemiological features of CL outbreaks in Libya including molecular identification of parasites, the geographical distribution of cases and possible scenarios of parasite transmission.

Methodology/Principal Findings

We studied 450 patients that came from 49 areas distributed in 12 districts in north-west Libya. The patients'' ages ranged from 9 months to 87 years (median age 25 years); 54% of the cases were males. Skin scrapings spotted on glass slides were collected for molecular identification of causative agent. The ribosomal internal transcribed spacer 1 (ITS1) was amplified and subsequently characterized by restriction fragment length polymorphism (RFLP) analysis. In total, 195 samples were successfully identified of which 148 (75.9%) were Leishmania major, and 47 (24.1%) Leishmania tropica. CL cases infected with L. major were found in all CL areas whereas L. tropica cases came mainly from Al Jabal Al Gharbi (46.4%), Misrata (17.8%) and Tarhuna districts (10.7%). A trend of seasonality was noticed for the infections with L. major which showed a clear peak between November and January, but was less pronounced for infections by L. tropica.

Conclusion

The first molecular study on CL in Libya revealed that the disease is caused by L. major and L. tropica and the epidemiological patterns in the different foci were the same as in other Mediterranean foci of CL.     

Effects of different combinations of benzyl adenine and indole acetic acid concentrations on in vitro plant regeneration in hexaploid wheat

Development of a reliable in vitro plant regeneration procedure for hexaploid bread wheat (Triticum aestivum L.) is a prerequisite for its improvement by genetic transformation. Here, we report the effects of two growth regulators, benzyl adenine (BA) and indole acetic acid (IAA) on callus induction and plant regeneration from scutellum cultures of two commercial bread wheat cultivars: Giza 164 and Sakha 69. Callus induction was obtained from isolated embryos cultured on modified Murashige and Skoog (MS) basal medium. After four weeks of callus induction, all calli were plated on MS basal medium for regeneration. Wheat genotype and callus induction medium played a dominant role in plantlet regeneration. 2.0 mg/L BA and 0.2 mg/L IAA were the best combinations for inducing callus and let to highest regeneration frequency (81.67%) across the cultivars. Overall, based on our medium conditions, Giza 164 displayed higher regeneration frequency (81.11%) than Sakha 69. These results will facilitate genetic transformation for the economic varieties Giza 164 and Sakha 69.