Simultaneous determination of chloroquine and metronidazole in human biological fluid by high pressure liquid chromatography

Chloroquine (CQ) and metronidazole (MZ) were measured in human urine and plasma by HPLC with UV detection. This method was used to analyse plasma levels in 4 African volunteers after an oral dose of 1000 mg CQ and 750 mg MZ, in a European on weekly prophylaxis of 500 mg CQ, and on 50 hospital urine samples. In the Africans peak plasma levels were over 1 microgram/ml and peak time was 1 1/2-2 hr. In the European plasma levels ranged from 0.58 to 0.36 microgram/ml. Over 80% of the urine samples contained CQ, MZ or both. The assay system was found flexible and economical for the therapeutic monitoring of these two important tropical drugs.     

STUDIES ON STRIGA SENEGALENSIS III. IN VITRO CULTURE OF SEEDLINGS. ESTABLISHMENT OF CULTURES

Striga senegalensis seeds were cultured on Knop's and modified Murashige-Skoog's medium. An aqueous root exudate/extract of the host (Sorghum vulgare) was found essential for the germination of seeds in vitro. The seedlings grew better on a medium containing sucrose than on mineral salts alone. Only limited growth was achieved on Knop's medium. Better growth was supported by Murashige-Skoog's medium. By transfer to larger culture vessels seedlings were kept in the latter for several months. The seedlings developed chlorophyllous shoots in light and flowered after 4–4½ months. The successful culture of these seedlings in a simple medium of only mineral salts and sugar indicates that the parasitic seedling depends on the host for only water, mineral salts and sugar and not for more elaborate substances.     

Exploring Consumer Perceptions and Economic Burden of Onchocerciasis on Households in Enugu State,South-East Nigeria

Introduction

Onchocerciasis or river blindness constitutes a major burden to households especially in resource-poor settings, causing a significant reduction in household productivity. There has been renewed interest from policy makers to reduce the burden of Neglected Tropical Diseases (NTDs) such as onchocerciasis on individuals and households. This paper provides new information on the patient’s perceptions of onchocerciasis and its economic burden on households in South-eastern Nigeria. The information will be useful to health providers and policy makers for evidence-informed resource allocation decisions.

Methods

Information was generated from a cross-sectional household survey conducted in Achi community, Oji River Local Government Area (LGA) of Enugu State, Southeast Nigeria. A pre-tested interviewer-administered questionnaire was used to collect data. A total of 747 households were visited randomly and data were collected using pre-tested interviewer administered questionnaire from 370 respondents. The respondents’ knowledge of the cause of symptoms of the disease, costs incurred for seeking treatment and productivity losses were elicited. Data were analyzed using tabulations and inferential statistics. A socio-economic status (SES) index was used to disaggregate some key variables by SES quintiles for equity analysis.

Results

Many people had more than one type of manifestation of onchocerciasis. However, more than half of the respondents (57%) had no knowledge of the cause of their symptoms. Male respondents had significantly more knowledge of the cause of symptoms than females (P = 0.04) but knowledge did not differ across SES (P = 0.82). The average monthly treatment cost per respondent was US$ 14.0. Drug cost (US$10) made up about 72% of total treatment cost. The per capita productivity loss among patients was US$16 and it was higher in the poorest (Q1) (US$20) and the third SES quintiles (Q3) (US$21). The average monthly productivity loss among caregivers was US$3.5.

Conclusion

Onchocerciasis still constitutes considerable economic burden on patients due to the high cost of treatment and productivity loss. Prioritizing domestic resource allocation for the treatment of onchocerciasis is important for significant and sustained reduction in the burden of the disease. In addition, focused health promotion interventions such as health education campaigns should be scaled up in onchocerciasis-endemic communities.     

CSF T-Tau/Aβ42 predicts white matter microstructure in healthy adults at risk for Alzheimer's disease

Cerebrospinal fluid (CSF) biomarkers T-Tau and Aβ(42) are linked with Alzheimer's disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF Aβ(42), total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/Aβ(42) were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/Aβ(42) levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter.     

Photoaffinity Labeling with 2-[2-(4-Azido-3-[125I]-Iodophenyl)ethylamino]adenosine and Autoradiography with 2-[2-(4-Amino-3-[125I]Iodophenyl)ethylamino]adenosine of A2a Adenosine Receptors in Rat Brain

Abstract: The A_2a adenosine receptor agonist 2-[2-(4-amino-3-iodophenyl)ethylamino]adenosine is a potent coronary vasodilator. The corresponding radioiodinated ligand, [¹²⁵I]APE, discriminates between high- and low-affinity conformations of A_2a adenosine receptors. In this study, [¹²⁵I]APE was used for rapid (24-h) autoradiography in rat brain sections. The pattern of [¹²⁵I]APE binding is consistent with that expected of an A_2a-selective radioligand. It is highest in striatum, nucleus accumbens, and olfactory tubercle, with little binding to cortex and septal nuclei. Specific [¹²⁵I]APE binding to these brain regions is abolished by 1 µ M 2- p -(2-carboxyethyl)phenethylamino-5'- N -ethylcarboxamidoadenosine (CGS-21680) but is little affected by 100 n M 8-cyclopentyl-1,3-dipropylxanthine. Conversion of [¹²⁵I]APE to the corresponding arylazide results in [¹²⁵I]AzPE. The rank-order potency of compounds to compete for [¹²⁵I]AzPE binding in the dark is CGS-21680 > d -( R )- N ⁶-phenylisopropyladenosine > N ⁶-cyclopentyladenosine, indicating that it also is an A_2a-selective ligand. Specific photoaffinity labeling by [¹²⁵I]AzPE of a single polypeptide (42 kDa) corresponding to A_2a adenosine receptors is reduced 55 ± 4% by 100 µ M guanosine 5'- O -(3-thiotriphosphate) and 91 ± 1.3% by 100 n M CGS-21680. [¹²⁵I]APE and [¹²⁵I]AzPE are valuable new tools for characterizing A_2a adenosine receptors and their coupling to GTP-binding proteins by autoradiography and photoaffinity labeling.     

Reclassification of "atypical" diagnoses in endoscopic retrograde cholangiopancreaticography-guided biliary brushings

OBJECTIVE: To evaluate the usefulness of reclassifying "atypical" diagnoses in reporting biliary cytology using strict morphologic criteria. STUDY DESIGN: Cytologic specimens from 139 patients (direct, alcohol-fixed smears or cytocentrifuge preparations) were evaluated. Diagnoses were benign (70), atypical (36) and malignant (33). Using strict criteria--major (nuclear contour, chromatin pattern) and minor (polarity, cell types, nuclear size, nuclear grooves, nucleoli, mitosis, nuclear/cytoplasmic [N/C] ratio)--atypical cases were reevaluated and reclassified. Follow-up (F/U) was available on all cases. RESULTS: Atypical cases, (36) were reclassified as malignant (26), atypical favor benign (2)/reactive (3) and atypical, not otherwise specified (NOS) (5). Cases reclassified as malignant showed irregular nuclear contours, chromatin irregularities and rare mitosis. Nuclear enlargement, nucleoli and cellularity varied widely in all groups. N/C ratio was increased in most reclassified malignant cases. All 26 malignant reclassifications correlated with F/U of malignancy. Benign and reactive cases (5) were negative for malignancy on F/U (4), and in 1 case a metastatic carcinoma involving the biliary tree was found. In the 5 atypical (NOS) cases, F/U showed malignancy (3) and pancreatitis (2). Cytocentrifuge preparations made in our laboratory were of superior quality when compared to other methods of cell preparation. CONCLUSION: Irregularities in nuclear membrane and abnormal chromatin pattern were the most consistently useful features correlating with malignancy. The sensitivity and specificity of biliary brush cytology can be enhanced by using strict cytomorphologic criteria and proper collection and fixation, all of which decrease atypical diagnoses.     

STUDIES ON THE GERMINATION OF SEEDS OF THE ROOT PARASITES,ALECTRA VOGELII AND STRIGA GESNERIOIDES. II. DNA SYNTHESIS AND DEVELOPMENT OF THE QUIESCENT CENTER IN THE RADICLE

DNA synthetic activity in the radicle meristem of embryos of germinating seeds of the obligate root parasites, Alectra vogelii and Striga gesnerioides was followed by autoradiography of ³H-thymidine incorporation. Incorporation of ³H-thymidine occurred in the nuclei of cells destined to form the vascular tissues, ground meristem and epidermis. An analysis of the distribution of labeled nuclei demonstrated the presence of a quiescent center of 2-4 cells in the radicle at the beginning of seed germination, becoming more prominent at later stages of germination. During continued growth of the radicle which resulted in a reduction in size of the meristem, cells of the original quiescent center were activated to undergo DNA synthesis.