In vitro substrate identification studies for p-glycoprotein-mediated transport: species difference and predictability of in vivo results

Two different cellular assay models were assessed as in vitro systems for P-glycoprotein (P-gp) substrate identification: cellular accumulation studies with KB-V1, a human MDR1 P-gp-overexpressing multidrug-resistant human epidermoid carcinoma cell line; and transcellular transport studies with L-MDR1 (or L-mdr1a), a human MDR1 (or mouse mdr1a)-transfected porcine renal epithelial cell line. The in vitro-in vivo correlation for P-gp-mediated transport activity was also examined by comparing in vitro data obtained from L-mdr1a cell studies and in vivo data from mdr1a (-/-)/(+/+) CF-1 mice studies for several compounds. The results are summarized as follows: 1) two in vitro assay systems routinely identified the substrate for human MDR1 P-gp-mediated transport with similar quantitative results; 2) in vitro studies with L-MDR1 and L-mdr1a cells demonstrated that the P-gp substrate susceptibility is different between human and mouse for certain compounds (species difference); and 3) in vivo brain concentration ratios of mdr1a (-/-) to (+/+) CF-1 mice, either at a certain time point or up to 60 min, correlated well with the in vitro transcellular transport ratios from L-mdr1a cells (r(2) = 0.968 and 0.926, respectively). This indicates that, at least in mice, the in vitro data are valid predictors of the in vivo contribution of P-gp: the contribution of P-gp to the distribution of the compound to the brain up to 60 min post i.v. administration. These results provide a rationale for predicting in vivo relevance of P-gp in human from in vitro data using human P-gp-expressing cells.     

Risk factors for anemia among pregnant women attending antenatal clinic at Jimma University Hospital, southwest Ethiopia

OBJECTIVE: to determine anemia and its risk factors among pregnant women METHODS: A cross-sectional analytic study was carried out among pregnant women who came for antenatal care follow up for the first time to Jimma University hospital, Jimma town, southwestern Ethiopia from May-June 2005. RESULTS: A total of 168 pregnant women who came for their first antenatal care visit to Jimma University hospital were enrolled in the study. A structured and interviewer administered questionnaire was used to collect data on the socio-demographic variables, dietary habit and other gynecologic and obstetric history. Dietary data were collected using food frequency questionnaire prepared for assessing nutritional factors for anemia. Sahli hemoglobinometer and a microscope were used for assessing hemoglobin level and stool for hookworm infection, respectively. Data were cleaned, edited and entered in to a computer and analyzed using SPSS for windows, version 11.0. Statistical tests were performed at the level of significance of 5%. The prevalence of anemia was 64/168 (38.2%) and the mean hemoglobin level was 11.3 mg/dl. Anemic cases were 4 times likely to have history of excess menstrual bleeding prior to the index pregnancy 2 times likely to have hook worm infection and 3 times likely not to have shoe wearing habit, 3 times likely to have birth intervals less than 24 moths between the previous pregnancy and index pregnancy (p < 0.05). CONCLUSION: This finding suggests the need for strengthening of interventions related to child spacing and raising awareness about family planning methods. All ANC attendants should be screened for anemia and hookworm infection at first visit and those anemic mothers and infected with hookworm should be treated appropriately. Health education should be given to pregnant mothers on family planning, and the need to gynecologic evaluation before pregnancy and the importance of wearing shoes to decrease hook worm infection and subsequent anemia.     

ASXL1 mutations are frequent and prognostically detrimental in CSF3R‐mutated chronic neutrophilic leukemia

Colony stimulating factor 3 receptor gene (CSF3R) mutations have recently been associated with chronic neutrophilic leukemia (CNL). Fourteen patients with CSF3R‐mutated CNL (median age 67 years; 57% males) were screened for additional mutations; 8 (57%) and 5 (38%) harbored an ASXL1 and/or SETBP1 mutation (two patients expressed both), respectively. Two patients developed blastic transformation, both SETBP1‐mutated and ASXL1‐unmutated, whereas two other cases evolved into chronic myelomonocytic leukemia (CMML), both ASXL1‐mutated and SETBP1‐unmutated. Median survival was 23.2 months (10 deaths documented). On multivariable analysis mutated ASXL1 (P = 0.009; HR 19.6, 95% CI 2.1–184.1) and thrombocytopenia (P = 0.005; HR 28.8, 95% CI 2.8–298.2) were independently predictive of shortened survival. This study provides information on the natural history of CSF3R‐mutated CNL and identifies mutant ASXL1 and thrombocytopenia as risk factors for survival. The study also suggests pathogenetic roles for SETBP1 and ASXL1 mutations in disease evolution into blast phase disease and CMML, respectively. Am. J. Hematol. 90:653–656, 2015. © 2015 Wiley Periodicals, Inc.     

Selective synthesis of visible light active γ-bismuth molybdate nanoparticles for efficient photocatalytic degradation of methylene blue,reduction of 4-nitrophenol,and antimicrobial activity

In this study, we have reported selective synthesis of bismuth molybdate (γ-Bi₂M₂O₆) nanoparticles (NPs) under different pH conditions for photocatalytic degradation of methylene blue (MB), reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) and antimicrobial activities. The synthesis of pure phase γ-Bi₂M₂O₆ at pH = 3 was confirmed by X-ray diffraction (XRD) and Raman analysis. A single hexagonal morphology was obtained at pH = 3 which shows the formation of the pure phase γ-Bi₂M₂O₆ NPs. The mixed morphologies (hexagonal and spherical) were observed at different pH values other than pH = 3. The bandgap energy of all the synthesized Bi₂M₂O₆ NPs is found in the visible region (2.48–2.59 eV). The photocatalytic activity of bismuth molybdate (BM) NPs was examined by the degradation of MB under visible light irradiation. Results show that 95.44% degradation efficiency was achieved by pure γ-Bi₂M₂O₆ NPs compared to mixed phases (γ-Bi₂M₂O₆, α-Bi₂M₂O₆ and β-Bi₂M₂O₆) synthesized at pH = 1.5 and 5. Moreover, the degradation efficiency of γ-Bi₂M₂O₆ was enhanced to 98.89% by the addition of H₂O₂. The effective catalytic activity of γ-Bi₂M₂O₆ was observed during the reduction of 4-NP to 4-AP by NaBH₄. Potential antibacterial and antifungal activity of γ-Bi₂M₂O₆ was observed, which gives a basis for further study in the development of antibiotics.

In this study, we have reported selective synthesis of γ-Bi₂M₂O₆ NPs under different pH conditions for photocatalytic degradation of methylene blue (MB), reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) and antimicrobial activities.     

Growth and form of provenances of Eucalyptus saligna at Wondo Genet,southern Ethiopia

A trial testing 10 provenances from across the natural range of Eucalyptus saligna and a local land race was established at Wondo Genet, southern Ethiopia. Eight years after planting, survival, tree height, diameter at breast height over bark, stem form, number of forks, height to the first fork, number of branches, branch diameter and branch angle were assessed. Volume per hectare was also calculated. Survival ranged between 36% (a provenance from 87 km north of Windsor, NSW) and 79% (Consuelo Tableland, Queensland), and differences were significant (P < 0.05). Among morphological characteristics, only the number of branches showed significant variation (P < 0.05), with the greatest number (12.4) being recorded for the Bulahdelah, NSW, provenance and the least (8.5) for the Clyde River, NSW, provenance. Major growth and morphological parameters (tree height, diameter, volume and stem form) did not differ significantly. The overall volume production (mean annual increment 26.4 m³ ha^?1) was well above the minimum acceptable growth observed on good sites elsewhere. Differences between provenances were small and mostly not significant, and no pattern of geographic variation was detected. Given the acceptable mean annual increment, those provenances represented by an adequate number of parent trees could be maintained for further selection and breeding, and to maintain genetic diversity of the species in Ethiopia.     

Hydrothermal green synthesis of MoS2 nanosheets for pollution abatement and antifungal applications

In this study, we report a green synthesis of MoS₂ nanosheets (NSs) using a facile hydrothermal technique in the presence of l-cysteine. l-Cysteine can serve as a greener source of sulfur as well as a capping agent to help the growth of MoS₂ nanosheets. The prepared materials were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS), electron transmission microscopy (TEM), X-ray photoelectron microscopy (XPS), and Brunauer, Emmett, and Teller (BET) analysis. The results showed that MoS₂ NSs are of high crystallinity with a lattice spacing of 0.61 nm. The optical bandgap of MoS₂ NSs nanosheets prepared using l-cysteine as a source of sulfur was found to be 1.79 eV. The photocatalytic degradation of MoS₂ NSs towards methylene orange (MO) and rhodamine blue (RB) dyes under sunlight was found to be promising for practical applications. The fast kinetics of degradation of MO and RhB was observed over a wide range of pH range. Moreover, MoS₂ NSs showed excellent antifungal activities against Trichophyton mentagrophytes and Penicillium chrysogenum fungus.

In this study, we report a green synthesis of MoS₂ nanosheets (NSs) using a facile hydrothermal technique in the presence of l-cysteine.     

Evaluation of functional recovery of recurrent laryngeal nerve using transoral laryngeal bipolar electromyography: a rat model

OBJECTIVES: We developed a standardized method of minimally invasive transoral laryngeal (ToL) bipolar electromyography (EMG) for evaluation of recurrent laryngeal nerve (RLN) recovery after a controlled crush injury in a rat model. METHODS: Ten 200- to 250-g Sprague-Dawley rats underwent a controlled crush injury to the left RLN performed with 60 seconds of use of a calibrated aneurysm clamp with a closing force of 0.61 N. Serial ToL bipolar EMG was performed on adductor muscles and the posterior criocoarytenoid muscle during spontaneous vocal fold motion under anesthesia. Each animal underwent ToL EMG immediately after surgery and 1, 3, and 6 weeks after surgery. RESULTS: The EMG signals showed normal motor unit potentials and recruitment patterns 3 weeks after crush injury. Endoscopic evaluation of vocal fold mobility yielded consistently normal findings 6 weeks after crush injury. CONCLUSIONS: We have developed a standardized method of crush injury to the rat RLN model and a minimally invasive transoral bipolar spontaneous EMG technique to serially evaluate and follow nerve injury and recovery in rats. This model is intended to simulate intraoperative RLN injury, to elucidate the electrophysiological events that occur during nerve recovery, and to form the basis for studying agents to enhance such recovery.     

Assessment of outpatient therapeutic programme for severe acute malnutrition in three regions of Ethiopia

OBJECTIVE: To document the experiences and lessons for rolling out of the OTP service at the wider scale with the aim of assessing the strengths and weaknesses of the project and suggest recommendations for future programming. DESIGN: Qualitative methods of data collection including focus group discussion, observation and in-depth interview of key informants were employed to get relevant data. Review of health facility, reports and programme documents were done to capture further- information. SETTING: Out Patient Programme (OTP) pilot programme implemented by CONCERN/ VALID in three administrative regions of Ethiopia namely: South Nations and Nationalities Peoples Regions (SPNNR), Addis Ababa and Oromia regions. A total of thirteen health centres which had started OTP service from the three regions were included in the study. SUBJECTS: Thirty six key informants and 30 focus group discussants were involved in the study conducted from 16th to 25th November 2006. RESULTS: Out Patient Programme (OTP) has enhanced community's understanding of malnutrition as a health problem through an excellent entry point it created for behaviour change communication (BCC) on optimal infant and young child feeding (IYCF). It has also enhanced utilisation of the existing equipments of the respective health services to promote nutrition and increased mental satisfaction of the providers who observed rapid recovery of malnourished children taking the plumpy nut. It also resulted in increased awareness of the community about malnutrition and its treatment, which resulted in increased need-based demand for the OTP and self-referral of children to health facilities. Shift in the thinking of the providers on the fact that malnutrition can be treated without admitting the child and reduction in the burden of malnutrition and associated mortality are other positive findings of the study. CONCLUSION: While it was observed that the programme was very effective in treating case of severe acute malnutrition and is highly acceptable by planners, health care providers and beneficiaries, there were different operational issues that needed to be strengthened. The irregularity and incompleteness of supply availability, high attrition of trained human power, inadequate supportive supervision especially from local ministry of health, inadequate community mobilisations are some of the shortcomings identified. Based of these findings recommendations were forwarded.