bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of pregnancy on HIV disease progression and survival among women in rural Uganda
Authors: Paal Lieve Van der , Shafer Leigh Anne , Mayanja Billy N. , Whitworth Jimmy A. G. , Grosskurth Heiner
Published: August 2010

Objective  To investigate the effect of pregnancy on HIV disease progression and survival among HIV‐infected women in rural Uganda, prior to the introduction of anti‐retroviral therapy (ART).

Methods  From a clinical cohort established in 1990, we selected records from HIV‐infected women of reproductive age. We conducted two analyses: (1) all HIV‐infected cases contributing to analysis of CD4 decline, using a linear regression model with random intercepts and slopes; (b) incident cases with known date of seroconversion contributed to analyses of median time to CD4 <200 cells/μl, AIDS and death.

Results  A total of 139 women were included in the analysis of CD4 decline. Women who subsequently became pregnant had higher CD4 counts at enrolment and had a slower CD4 decline than those who did not become pregnant. In women who became pregnant, CD4 decline was faster after pregnancy than before (P < 0.0001). The survival analyses showed no significant differences between women who became pregnant and those who did not with respect to median time to CD4 count <200, AIDS or death.

Conclusions  The initial comparative immunological advantage possessed by fertile women before they become pregnant is subsequently lost as a result of their pregnancy. Women should be informed about the potential negative effect of pregnancy on their immunological status and should be offered contraception. In resource‐limited settings, women determined to become pregnant should be given priority for ART if eligible.
Intermittent preventive treatment of malaria in pregnancy: the effect of new delivery approaches on access and compliance rates in Uganda
Authors: Mbonye Anthony K. , Magnussen Pascal , Bygbjerg I. B.
Published: August 2010

Objective  To assess whether traditional birth attendants, drug‐shop vendors, community reproductive health workers and adolescent peer mobilizers can administer intermittent preventive treatment (IPT) with sulfadoxine‐pyremethamine to pregnant women, and reach those most at risk of malaria and increase access and compliance to it.

Methods  The study was designed to assess new approaches of delivering IPT through these groups and compare it with IPT at health units. The primary outcome measures were: the proportion of adolescents and primigravidae accessed; gestational age at recruitment and the proportion of women who completed two doses of sulfadoxine‐pyremethamine.

Results  Two thousand seven hundred and eighty‐five pregnant women (78% of those in the study area) participated. With new approaches, 92.4% of the women received IPT during the second trimester as recommended by the policy, vs. 76.1% at health units, P < 0.0001. Of the women who received two doses of sulfadoxine‐pyremethamine, 39.9% were at health units (control) vs. 67.5% through new approaches (P < 0.0001). Women using the new approaches also accessed IPT early: the mean gestational age when receiving the first dose of sulfadoxine‐pyremethamine was 21.0 weeks vs. 23.1 weeks at health units (P < 0.0001). However, the health units were used by a higher proportion of primigravidae (23.6%vs. 20.0%, P < 0.04), and this was also the case for adolescents (28.4%vs. 25.0%, P < 0.03). This intervention was acceptable with 89.1% of the women at the new approaches intending to use IPT in future.

Conclusions  The new approaches increased access to and compliance with IPT. We recommend a review of the policy to allow the provision of IPT through the new approaches.
The effect of health care worker training on the use of intermittent preventive treatment for malaria in pregnancy in rural western Kenya
Authors: Ouma P. O. , Van Eijk A. M. , Hamel M. J. , Sikuku E. , Odhiambo F. , Munguti K. , Ayisi J. G. , Kager P. A. , Slutsker L.
Published: August 2010

Background  In 1998, Kenya adopted intermittent preventive treatment (IPTp) with sulphadoxine‐pyrimethamine (SP) for malaria prevention during pregnancy. We conducted a survey in 2002 among women who had recently delivered in the rural neighbouring areas Asembo and Gem and reported coverage of 19% of at least one dose and 7% of two or more doses of SP. Health care workers (HCW) in Asembo were retrained on IPTp in 2003.

Objectives  To evaluate if IPTp coverage increased and if the training in Asembo led to better coverage than in Gem, and to identify barriers to the effective implementation of IPTp.

Methods  Community‐based cross‐sectional survey among a simple random sample of women who had recently delivered in April 2005, interviews with HCW of antenatal clinics (ANC) in Asembo and Gem.

Results  Of the 724 women interviewed, 626 (86.5%) attended the ANC once and 516 (71.3%) attended two or more times. Overall IPTp coverage was 41% for at least one dose, and 21% for at least two doses of SP. In Asembo, coverage increased from 19% in 2002 to 61% in 2005 for at least one dose and from 7% to 17% for two doses of SP. In Gem, coverage increased from 17% to 28% and 7% to 11%, respectively. Interviews of HCW in both Asembo and Gem revealed confusion about appropriate timing, and lack of direct observation of IPTp.

Conclusion  Training of HCW and use of simplified IPTp messages may be a key strategy in achieving Roll Back Malaria targets for malaria prevention in pregnancy in Kenya.
Comparison of visual inspection and Papanicolau (PAP) smears for cervical cancer screening in Honduras: should PAP smears be abandoned?
Authors: Perkins R. B. , Langrish S. M. , Stern L. J. , Figueroa J. , Simon C. J.
Published: August 2010

Objective  To compare visual inspection with acetic acid (VIA) to Papanicolau (PAP) smears in a community setting in a developing nation.

Methods  Women undergoing cervical cancer screening in Honduras received either VIA and PAP smears (VIA/PAP group) or PAP smears alone (PAP‐only group). Local healthcare providers performed PAP screening. A VIA‐trained nurse performed VIA exams. All PAP smears were processed in Honduras. PAP smears from the VIA/PAP group were reviewed in the United States. Women with positive VIA or PAP tests were offered colposcopy. We compared the relative accuracy of PAP smears and VIA and the proportions of women completing follow‐up colposcopy after positive screening tests.

Results  In total, 1709 PAP smears were performed including women from both the VIA/PAP and PAP‐only groups. Nine PAP smears were positive (0.5%). Three women completed colposcopy (33%). All three had biopsy‐confirmed dysplasia. In the VIA/PAP group (n = 339), 49 VIA exams were abnormal (14%) and two PAP smears were abnormal when read in Honduras (0.6%). When reviewed in the United States, 14 of the 339 PAP smears were abnormal (4%). Forty women (83%) completed follow‐up colposcopy after a positive VIA exam. Twenty‐three had biopsy‐proven dysplasia. All 23 dysplasia cases had negative PAP smear readings in Honduras; four PAP smears were reclassified as positive in the United States.

Conclusions  Although few developing countries can maintain high‐quality PAP smear programmes, many governments and charitable organizations support cervical cancer screening programmes that rely on PAP smears. This study underscores the need to promote alternative technologies for cervical cancer screening in low‐resource settings.
Mortality of sick children after outpatient treatment at first‐level health facilities in rural western Kenya
Authors: Lindblade Kim A. , Hamel Mary J. , Feikin Daniel R. , Odhiambo Frank , Adazu Kubaje , Williamson John , Vulule John M. , Slutsker Laurence
Published: August 2010

Objectives  (1) To determine whether mortality rates were raised in sick children in the 30 days after visiting first‐level health facilities in an area under demographic surveillance in western Kenya, (2) to identify the types of illnesses associated with increased mortality and (3) to estimate the effectiveness of appropriate treatment.

Methods  All sick children (2–59 months of age) who attended one of the seven participating first‐level health facilities from May to August 2003 were identified. A standardized mortality ratio was computed to compare their mortality rate in the 30 days after a sick visit with that of the community under active demographic and health surveillance. A multivariate Cox Proportional Hazards model was used to identify illnesses associated with death and to estimate the protective effectiveness of appropriate treatment for potentially life‐threatening diseases.

Results  A total of 1383 eligible children made 1697 sick visits; 33 (2.4%) died within 30 days. Compared with children 2–59 months in the general population, sick children had a 5.3 times greater mortality rate [95% confidence interval (CI) 3.8–7.5]. In a multivariate survival analysis, significant risk factors for mortality included age <24 months [Hazard Ratio (HR) 4.4, 95% CI 1.5–12.6], malnutrition (HR 15.5, 95% CI 6.1–39.8), severe pneumonia (HR 12.9, 95% CI 3.0–56.4) and anaemia (HR 3.3, 95% CI 1.5–7.2). Appropriate treatment for a child’s most severe illness reduced mortality by 78% (95% CI 57–89%).

Conclusion  We estimate that improvements in diagnosis and appropriate treatment at first‐level health facilities for children 2–59 months could reduce overall under‐5 mortality in the area by 12–14%.
Nutritional status, psychological well‐being and the quality of life of AIDS orphans in rural Henan Province, China
Authors: He Zhonghu , Ji Chengye
Published: August 2010

Objective  To assess the influence of orphanhood due to AIDS on children’s nutritional status, psychological well‐being and life quality, and to explore appropriate intervention strategies in China.

Methods  In 2005, 186 children aged 8–15 years (93 AIDS orphans and 93 non‐orphans) from a rural area of Henan Province were surveyed in a cross‐sectional and matched pairs study on nutritional status, psychological health and life quality.

Results  We found no compelling evidence for poorer nutritional status in orphans. The nutritional status of both orphans and non‐orphans was extremely poor according to the prevalence of stunting, underweight, wasting and anaemia. Depression, low self‐esteem and lower quality of life were more frequent in orphans. These differences mainly existed in boys’ groups. No significant differences were found between paternal, maternal and double orphans, or orphans in orphanages or extended families. Regression analysis revealed that orphanhood leads to low self‐esteem and more depression which contributes to lower quality of life and mediates the association between orphanhood and quality of life.

Conclusion  The high prevalence of poor nutritional status indicates that basic material needs of children, including AIDS orphans, are not met in rural China. Psychological problems were prominent among orphans and had become the most important contributor of lower life quality. Boys were at least as vulnerable as girls. The living conditions of all children in rural China must be improved; school‐based care and support are crucial and would be a cost‐effective way to improve the overall life quality of AIDS orphans.
Taxonomy and inventory of the cytospecies and cytotypes of the Simulium damnosum complex (Diptera: Simuliidae) in relation to onchocerciasis
Authors: Post R. J. , Mustapha M. , Krueger A.
Published: August 2010

We provide an inventory of all named cytoforms of the Simulium damnosum complex (including those which are now considered invalid), along with all inversions that have been recorded (including synonyms and homonyms). There are 55 valid and distinct cytoforms known from the S. damnosum complex making it the largest sibling species complex of any vectors, and probably of any insect or other animal. All cytoforms are listed along with their fixed and diagnostic inversions and country distribution. There are 183 inversions known from the complex as a whole, of which 49% are fixed and/or diagnostic between cytoforms, and the fixed/diagnostic inversions seem to occur disproportionately on chromosome arm 2L.
Wastewater‐irrigated vegetables: market handling versus irrigation water quality
Authors: Ensink Jeroen H. J. , Mahmood Tariq , Dalsgaard Anders
Published: August 2010

Objective and methods  Vegetables irrigated with untreated domestic wastewater were, at the time of harvest, analysed for the presence of the faecal indicator, Escherichia coli, and helminth eggs in Faisalabad, Pakistan. Vegetables from the same harvested batch were collected approximately 12 h later from the local market.

Results  The survey found relatively low concentrations of E. coli (1.9 E. coli per gram), but relatively high concentrations of helminths (0.7 eggs per gram) on vegetables collected from agricultural fields. Higher concentration of both E. coli (14.3 E. coli per gram) and helminths (2.1 eggs per gram) were recovered from the vegetables collected from the market.

Conclusions  The results of the survey suggest that unhygienic post harvest handling was the major source of produce contamination. Interventions at the market, such as the provision of clean water to wash produce in, are better ways to protect public health and more cost effective than wastewater treatment.
Effectiveness of common and improved sanitary washing methods in selected cities of West Africa for the reduction of coliform bacteria and helminth eggs on vegetables
Authors: Amoah P. , Drechsel P. , Abaidoo R. C. , Klutse A.
Published: August 2010

Objective  To analyse and improve the effectiveness of common indigenous washing methods for the reduction of faecal coliform (FC) populations on the surface of wastewater‐irrigated vegetables and to determine simple factors affecting their efficacy.

Methods  Questionnaire interviews were used to gather information on common methods used for washing vegetables in seven West African countries. The efficacy of the most common decontamination methods was measured in terms of log reductions in FC populations on homogenised contaminated lettuce, cabbage and spring onion samples.

Results  The large majority of urban households and restaurants in the subregion are aware of vegetable‐related health risks and wash vegetables before consumption. Methods used vary widely within and between Ghana and neighbouring francophone West African countries. However, several of the most common methods do not reduce the contamination to any desirable level. Significantly, different log reductions are achieved depending on the washing method, contact time and water temperature. Tests to improve the apparent ineffective methods were especially promising in view of the relatively expensive vinegar. However, up to 3 log units reduction is also possible at a much lower price with ‘Eau de Javel’ (household bleach), which is commonly used in francophone West Africa.

Conclusion  Washing vegetables before consumption is an important component of a multiple barrier approach for health risk reduction. The high risk perception among consumers demands that more information be made available on the appropriate use of these washing methods. Any washing method will need complementary efforts to reduce contamination before the vegetables enter the kitchen, such as safer irrigation practices.
The relative contribution of case management and inadequate care‐seeking behaviour to childhood deaths from diarrhoea and acute respiratory infections in Hidalgo, Mexico
Authors: Bojalil Rossana , Kirkwood Betty R , Bobak Martin , Guiscafre Hector
Published: August 2010

Objective  To investigate the contribution of poor case management and care‐seeking behaviour to childhood deaths from acute respiratory infections (ARI) and diarrhoeal diseases in rural Mexico.

Methods  Eighty‐nine deaths from ARI and diarrhoea in under‐fives from Hidalgo over a 7‐month period were identified from registered death certificates. We interviewed the carers of 75 of these children, eliciting what happened before death, including signs and symptoms, contact with health services, details on treatments and details of doctors. These death narratives were used to assess the contributions of care seeking and case management to the childhood deaths. We conducted an independent investigation of the clinical competence of doctors mentioned in the death narratives using standard case scenarios and compared this with results obtained from neighbourhood control doctors.

Results  Late care seeking and/or poor case management contributed to 68% of deaths. The estimated contribution of care seeking alone was 32%, of case management alone 17% and of both care seeking and case management 18% of deaths. Doctors implicated as having contributed to a child’s death had significantly lower clinical competence scores than those who were not. Private doctors accounted for 1.4 times more consultations prior to death than public doctors, but were implicated in 1.8 times the number of deaths.

Conclusion  Efforts to reduce child mortality need to improve both care seeking for childhood illnesses and quality of case management. It is essential that doctors in the private sector be included, as in Mexico and many other countries they provide a large proportion of care, often with adverse outcomes.
Low prevalence of HIV and other sexually transmitted infections in young women attending a youth counselling service in Maputo, Mozambique
Authors: Melo Josefa , Folgosa Elena , Manjate Delfina , Osman Nafissa , Francois Isabelle , Temmerman Marleen , Cappuccinelli Piero , Colombo Mauro M.
Published: August 2010

Objectives  To determine the prevalence of sexually transmitted infections (STIs) in a group of young women attending the Adolescent and Youth Friendly Service, in Maputo, Mozambique, and to evaluate their level of knowledge, practices and attitudes about STI.

Methods  A total of 445 women voluntarily participated in the study and filled in a self‐administered knowledge, practices and attitudes (KAP) questionnaire; 435 of them underwent a laboratory examination for vaginosis, candidiasis, trichomoniasis, gonorrhoea, chlamydiosis, syphilis and HIV infection.

Results  Women had a high level of awareness and knowledge of STI and HIV. Candidiasis was the most prevalent reproductive tract infection (36%), followed by vaginosis (13%) and trichomoniasis (7.6%), and sexually transmitted diseases. HIV seroprevalence was 4%; 42% were negative in all tests.

Conclusion  The low prevalence of STI and HIV may be related in part to the high level of awareness registered in the group.
Risk associated with asymptomatic parasitaemia occurring post‐antimalarial treatment
Authors: Olliaro Piero , Pinoges Loretxu , Checchi Francesco , Vaillant Michel , Guthmann Jean‐Paul
Published: August 2010

Objective  Parasites may recur asymptomatically after initial clearance by antimalarial treatment. Current guidelines recommend treatment only when patients develop symptoms or at the end of follow‐up. We wanted to assess prospectively the probability of becoming symptomatic and the risks of this practice.

Methods  We analysed data collected in 13 trials of uncomplicated paediatric malaria conducted in eight sub‐Saharan African countries. These studies followed all cases of post‐treatment asymptomatic parasitaemia until they developed symptoms or to the end of the 28‐day follow‐up period, at which time parasite genotypes were compared to pre‐treatment isolates to distinguish between recrudescences and new infections.

Results  There were 425 asymptomatic recurrences after 2576 treatments with either chloroquine, sulfadoxine/pyrimethamine or amodiaquine, of which 225 occurred by day 14 and 200 between day 15 and day 28. By day 28, 42% developed fever (median time to fever = 5 days) and 30% remained parasitaemic but afebrile, while 23% cleared their parasites (outcome unknown in 4%). Young age, parasitaemia ≥500 parasites/μl; onset of parasitaemia after day 14, and treatment with amodiaquine were the main variables associated with higher risk of developing fever.

Conclusion  In areas of moderate to intense transmission, asymptomatic recurrences of malaria after treatment carry a substantial risk of becoming ill within a few days and should be treated as discovered. Young children are at higher risk. The higher risk carried by cases occurring in the second half of follow‐up may be explained by falling residual drug levels.
Translation of artemether–lumefantrine treatment policy into paediatric clinical practice: an early experience from Kenya*
Authors: Zurovac D. , Njogu J. , Akhwale W. , Hamer D. H. , Snow R. W.
Published: August 2010

Objective  To describe the quality of outpatient paediatric malaria case‐management approximately 4–6 months after artemether–lumefantrine (AL) replaced sulfadoxine–pyrimethamine (SP) as the nationally recommended first‐line therapy in Kenya.

Methods  Cross‐sectional survey at all government facilities in four Kenyan districts. Main outcome measures were health facility and health worker readiness to implement AL policy; quality of antimalarial prescribing, counselling and drug dispensing in comparison with national guidelines; and factors influencing AL prescribing for treatment of uncomplicated malaria in under‐fives.

Results  We evaluated 193 facilities, 227 health workers and 1533 sick‐child consultations. Health facility and health worker readiness was variable: 89% of facilities stocked AL, 55% of health workers had access to guidelines, 46% received in‐service training on AL and only 1% of facilities had AL wall charts. Of 940 children who needed AL treatment, AL was prescribed for 26%, amodiaquine for 39%, SP for 4%, various other antimalarials for 8% and 23% of children left the facility without any antimalarial prescribed. When AL was prescribed, 92% of children were prescribed correct weight‐specific dose. AL dispensing and counselling tasks were variably performed. Higher health worker’s cadre, in‐service training including AL use, positive malaria test, main complaint of fever and high temperature were associated with better prescribing.

Conclusions  Changes in clinical practices at the point of care might take longer than anticipated. Delivery of successful interventions and their scaling up to increase coverage are important during this process; however, this should be accompanied by rigorous research evaluations, corrective actions on existing interventions and testing cost‐effectiveness of novel interventions capable of improving and maintaining health worker performance and health systems to deliver artemisinin‐based combination therapy in Africa.
Human and porcine neurocysticercosis: differences in the distribution and developmental stages of cysticerci
Authors: Sáenz B. , Ramírez J. , Aluja A. , Escobar A. , Fragoso G. , Morales J. , Pérez‐Tamayo R. , Rosetti F. , Larralde C. , Sciutto E. , Fleury A.
Published: August 2010

Objective  To describe and compare the clinical impacts of neurocysticercosis (NC) caused by Taenia solium in humans and pigs.

Methods  Comparative study of the brains of 16 asymptomatic pigs and 35 human NC cases (15 asymptomatic and 20 symptomatic).

Results  In humans, cysticerci were more frequently located in the ventricles and subarachnoid space at the base of the brain (11.8%vs. 1.6%; P = 0.001 and 25.9%vs. 0%; P < 0.0001, respectively) while in pigs, cysticerci were more frequently found in the parenchyma (44.4%vs. 7.6%; P < 0.0001). In human brains, 75.9% of the cysticerci were calcified, while in pigs all cysticerci were in the vesicular stage.

Conclusion  The duration of infection and the host–parasite relationship (such as immune reactivity and brain haemodynamics) differ between humans and pigs. This may account for the different distribution and stage of the cysticerci among humans and pigs.
Accidental paraffin poisoning in Kenyan children
Authors: Lang T. , Thuo N. , Akech S.
Published: August 2010

A serious and common accident in rural Kenyan homesteads is accidental ingestion of paraffin when it has been mistaken for water and offered to a young child. Here we report the incidence, parental practices and outcome of severe paraffin poisoning, requiring admission at Kilifi District Hospital, Kenya. Over a 2‐year period, 48 children (0.5% of all admissions) were admitted with kerosene poisoning, constituting 62% of all poisoning cases. All cases were accidental. Ten per cent had induced vomiting. One child (2%) died. We suggest these data support assessment followed by implementation of practical and affordable measures to prevent paraffin poisoning.
Estimates of the economic burden of rotavirus‐associated and all‐cause diarrhoea in Vellore, India
Authors: Mendelsohn Andrea S. , Asirvatham Jaya Ruth , Mkaya Mwamburi D. , Sowmynarayanan T. V. , Malik Vandana , Muliyil Jayaprakash , Kang Gagandeep
Published: August 2010

Objective  To determine the cost of rotavirus and all‐cause diarrhoea in Vellore, India.

Methods  Parents of children <5 years of age accessing clinics, emergency rooms, or hospitals for acute diarrhoea completed a questionnaire detailing healthcare utilisation, medical and non‐medical expenditures, and lost income. Faecal samples were screened for rotavirus and medical records were examined. Costs were estimated for inpatient and outpatient resource consumption, stratified by facility.

Results  Total societal costs of a hospitalised diarrhoeal episode were Rs 3278.50 (US$ 80.80) at a large referral hospital and Rs 1648.60 (US$ 40.60) at a smaller community hospital. Costs for rotavirus positive or negative gastroenteritis were similar. Median household expenditures per diarrhoeal episode at the referral and the community hospitals equalled 5.8% and 2.2% of the annual household income, respectively.

Conclusions  Diarrhoeal disease in children constitutes a considerable economic burden. An appropriately priced and effective rotavirus vaccine may provide significant economic savings for the Indian household and healthcare system.
Synthesis and cystine/cysteine‐catalyzed oxidative folding of the Amaranth α‐amylase inhibitor
Authors: LOZANOV VALENTIN , GUARNACCIA CORRADO , PATTHY ANDRÁS , FOT SALVATORE , PONGOR SÁNDOR
Published: August 2010

We report here the total synthesis of the α‐amylase inhibitor (AAI), a 32‐residue‐long peptide with three disulfide bridges, isolated from amaranth seeds (Chagolla‐Lopez, A., Blanco‐Labra, A., Patthy, A., Sanchez, R. & Pongor S. (1994)J. Biol. Chem.269, 23675–23680). The synthesis was carried out using a stepwise solid‐phase approach based on the Fmoc/t‐Bu chemistry, combined with theS‐acetamidomethyl protection for cysteines. The linear, reduced peptide was obtained after two reduction steps, using 1, 4‐dithio‐dl‐threitol and tri(2‐carboxyethyl)phosphine hydrochloride in basic and acidic conditions, respectively. Disulfide bridges were formed by oxidative folding in a cystine/cysteine redox buffer, these conditions were found superior to air oxidation and to glutathione‐catalyzed oxidative folding. The physicochemical and enzyme inhibitory properties of synthetic AAI were found identical with those of the natural product. Several orthogonal protection schemes proved unsuccessful in obtaining a biologically active product.
Comparative evaluation of different methods for disulfide bond formation in synthesis of the HIV‐2 antigenic determinant
Authors: KUDRYAVTSEVA E.V. , SIDOROVA M.V. , OVCHINNIKOV M.V. , BESPALOVA Zh.D. , BUSHUEV V.N.
Published: August 2010

The peptide H‐Asn‐Ser‐Trp‐Gly‐Cys‐Ala‐Phe‐Arg‐Gln‐Val‐Cys‐NHEt corresponding to the 593–603 sequence of gp41 protein of the HXV‐2 was used to evaluate different methods for the removal of Acm‐protection and subsequent disulfide bond formation. The studied methods involved the treatment by salts of heavy metals (silver and mercury) and subsequent cyclization by oxygen, potassium ferricyanide or hydrogen peroxide. The direct oxidative conversion of Acm‐peptide to the corresponding cyclic disulfide by iodine under acidic and neutral conditions was investigated, and the structure of by‐products was also studied. The best results were obtained using mercuric acetate followed by oxidation with hydrogen peroxide. © Munksgaard 1997.
Cyclotetrapeptides and cyclopentapeptides: occurrence and synthesis*
Authors: SCHMIDT ULRICH , LANGNER JÖRG
Published: August 2010

The structures reported for the three cancerostatic all‐l‐cyclotetrapeptides cyclo(Pro‐Leu)2, cyclo(Pro‐Val)2 and cyclo(Pro‐Phe)2 isolated from a tunicate seem questionable. The synthetic compounds claimed to be identical to the naturally occurring cyclotetrapeptides are in fact not cyclotetrapeptides but rather cyclooctapeptides.

We have not been able to prepare the tyrosinase inhibitor cyclo(Pro‐Val‐Pro‐Tyr). Ring closure of H‐Pro‐Val‐Pro‐Tyr‐OC6F5 gave rise to 31% of cyclo(Pro‐Val‐Pro‐d‐Tyr). The same product was obtained in 53% yield from H‐Pro‐Val‐Pro‐d‐Tyr‐oc6F5.

For the ring closure to the all‐l‐cyclopentapeptide cyclo(Pro‐Ala‐Ala‐Phe‐Leu), all ring closure positions have been investigated. The reaction at the nitrogen atom of leucine leads to 21% of the all‐l‐cyclopentapeptide. Dimers or mixtures of monomers and dimers result from reaction at all other positions. © Munksgaard 1997.
Improvements in automated PNA synthesis using Boc/Z monomers
Authors: KOCH TROELS , HANSEN HENRIK F. , ANDERSEN PETER , LARSEN TINNA , BATZ HANS G. , OTTESON KENNETH , ØRUM HENRIK
Published: August 2010

An optimized automated PNA synthesis protocol is reported. Under optimal conditions the product yield of a test 17‐mer PNA is approximately 90%. The average coupling yield is 99.4%. The synthesis strategy is Boc/Z and the deprotected amine is neutralized in situ. The monomers are added in molar excess to HATU and pre‐activated for 60 s before delivery to the resin. The concentration of the activated monomers is 0.08 m during the couplings. Heteroselective solvation provides the highest coupling yields. Acetic anhydride is used as capping reagent followed by a piperidine wash. The protocol has been developed in a 5 μmol scale but is easily scaled up to 10–50 μmol scale syntheses on the automated synthesizer (ABI 433A). © Munksgaard 1997.
Gastroenteropancreatic effects of xenin in the dog
Authors: FEURLE GERHARD E. , HEGER MARIT , NIEBERGALL‐ROTH ELKE , TEYSSEN STEPHAN , FRIED MICHAEL , EBERLE CHARLOTTE , SINGER MANFRED V. , HAMSCHER GERD
Published: August 2010

Xenin is a 25 amino acid peptide detected in the gastric mucosa of various mammals. It has since been found in low concentrations in other tissues. Xenin plasma concentrations increase after meals. The present study reports some gastroenteropancreatic effects of this peptide in the dog. Intravenous infusion of 64 pmol/kg min synthetic xenin significantly inhibited pentagastrin‐stimulated gastric acid secretion and stimulated exocrine pancreatic secretion of volume and protein. Further, intravenous infusion of xenin in a dose of 1.0 pmol/kg min stimulated jejunal motility in the anaesthetized dog. An intravenous infusion of 32 pmol/kg min xenin raised plasma concentrations of pancreatic polypeptide, vasoactive intestinal polypeptide, insulin and glucagon. The present experiments therefore indicate manifold bioactive properties of intravenously infused xenin in the dog, with jejunal motility the most sensitive target. Conclusions as to the physiological role of xenin cannot be drawn from the present experiments. The release of other hormonal peptides indicates a complex action of xenin. © Munksgaard 1997.
Solid‐phase peptide synthesis at elevated temperatures: a search for an optimized synthesis condition of unsulfated cholecystokinin‐12
Authors: VARANDA LEANDRO M. , MIRANDA M. TERÊSA M.
Published: August 2010

A systematic investigation of solid‐phase peptide synthesis at elevated temperatures using the well‐known aggregating peptide acyl carrier protein (65–74) and the unsulfated cholecystokinin‐8 as models is presented. The main goal of the investigation was the determination of an optimized experimental condition for the synthesis of unsulfated cholecystokinin‐12. Of the elevated temperatures used, 60°C was the most appropriate. The efficiency of N, N'‐diisopropylcarbodiimide/l‐hydroxybenzotriazole (DIC/HOBt) in 25% dimethyl sulfoxide (DMSO)/toluene at this temperature was similar to that of 2‐(1‐H‐benzotriazole‐1‐yl)‐1, 1, 3, 3‐tetramethyluronium tetrafluoroborate (TBTU). Interestingly, this coupling reagent was more efficient than TBTU, benzotriazol‐1‐yl oxy‐tris(dimethylamino)phosphonium and O‐(7‐azabenzotriazol‐1‐yl)‐1, 1, 3, 3‐tetramethyluronium hexafluorophosphate in N‐methylpyrrolidone. 25%DMSO/toluene proved to be suitable for the swelling of the resins phenylacetamidomethyl, methylbenzhydrylamine, hydroxymethylphenoxy, 4‐(benzyloxy)‐2′, 4′‐dimethoxybenzhydrylamine, 4‐(2′, 4′‐dimethoxyphenyl‐Fmoc‐aminomethyl)phenoxy and (4‐succinylamido‐2′, 2′, 4′‐trimethoxy)benzhydrylamine. Those polymeric supports were fully compatible with the approach. Under the optimized synthesis condition found in these studies (temperature of 60°C, DIC/HOBt as coupling reagent and 25%DMSO/toluene as solvent), no difficulties related to the aggregation phenomenon were encountered. These data confirm the usefulness of solid‐phase peptide synthesis at elevated temperatures and extend its applicability.
The solid‐phase synthesis of side‐chain‐phosphorylated peptide‐4‐nitroanilides
Authors: BERNHARDT ANNE , DREWELLO MARIO , SCHUTKOWSKI MIKE
Published: August 2010

Peptide‐4‐nitroanilides can be quickly synthesised using an Fmoc‐based approach on 2‐chlorotritylchloride resin. Preformed building blocks Fmoc‐Xaa‐NH‐Np (Xaa = Cit, Cys, Gin, His, Lys, Orn, Ser, Thr, Tyr, Trp) can be attached via side chain to the 2‐chlorotritylchloride linker of the resin. N‐terminal elongation yields the respective peptide‐4‐nitroanilides after detachment from the solid support. We synthesised a set of tetrapeptide‐4‐nitroanilides with the general structure Suc‐Ala‐Phe‐Pro‐Xaa‐NH‐Np (Xaa = Asp, Cit, Cys, Glu, Gin, His, Lys, Orn, Ser, Thr, Tyr, Trp). Even peptidyl‐arginine‐4‐nitroanilides are available by a slightly modified procedure. First, the appropriate ornithine‐containing peptide was synthesised. After detachment of the peptide from the resin the side‐chain primary amino group was transformed to the guanidino function of arginine using 1‐guanyl‐3, 5‐dimethylpyrazole. A further application of this method is the convenient synthesis of phosphorylated peptide‐4‐nitroanilides. Five phosphopeptides with the general structure Ac‐Ala‐Xaa(PO3H2)‐Pro‐Yaa‐NH‐Np (Xaa = Ser, Thr, Tyr; Yaa = Tyr, Lys) and their nonphosphorylated analogues were prepared. Global phosphorylation was carried out on the resin‐bound peptides using dibenzyl‐N, N‐diisopropyl‐phosphoramidite/tetrazole followed by oxidation with tert‐butyl hydroperoxide. © Munksgaard 1997.
Substance P derivatives with photoactivatable labels in the N‐terminal part of the molecule
Authors: KASHEVEROV IGOR E. , UTKIN YURI N. , FRANKE PETER , TSETLIN VICTOR I.
Published: August 2010

Photoactivatable substance P (SP) derivatives containing thep‐benzoylbenzoic moiety at the N‐terminal α‐amino group of Arg 1 or at the ε‐amino group of Lys 3 were prepared. Both derivatives also had ap‐hydroxyphenylpropionyl group for radioiodination. To obtain the analogue with the photolabel at Arg 1, SP was first reacted withN‐hydroxysuccinimidep‐hydroxyphenylpropionate, the Lys 3‐modified derivative was isolated by reversed‐phase high‐performance liquid chromatography (HPLC), reacted withN‐hydroxysuccinimidep‐benzoylbenzoate and purified by HPLC. To place the photolabel at Lys 3, the order of the reactions was reversed. The structure of the derivatives obtained was confirmed by mass spectrometry. The interaction of the derivatives obtained and of their125I‐labeled forms with the NK‐1 neurokinin receptor from the rat brain, as well as with the nicotinic acetylcholine receptor fromTorpedoelectrocytes was analyzed. The results obtained supported by the data from the literature indicate that benzoylbenzoic acid derivatives should not be considered as universal photolabels, which ensure in all cases a high level of photo‐cross‐linking.
Structure‐antitumor and hemolytic activity relationships of synthetic peptides derived from cecropin A‐magainin 2 and cecropin A‐melittin hybrid peptides
Authors: SHIN SONG YUB , LEE MYUNG KYU , KIM KIL LYONG , HAHM KYUNG‐SOO
Published: August 2010

The hybrid peptide (CA‐ME) derived from cecropin A(1–8) and melittin(1–12) has potent antibacterial and antimalarial activities. Because the N‐terminal sequence 1–12 of magainin 2 is similar to melittin(1–12), CA‐MA with CA(1–8) and MA(1–12) and their analogues were designed and synthesized. Antitumor activities of these peptides were evaluated using three small cell lung cancer cell lines. Greater antitumor activity was observed when the residues 16, 18 and 19 of the peptide were hydrophobic (Leu or Val), basic (Lys) and basic (Lys), respectively. The IC50 values of the peptides with the residues were 2 to 4 μm. Residue 12 was related to hemolytic activity rather than antitumor activity. Increase in amphipathicity of P4 enhanced hemolytic activity without significant change in antitumor activity. The α‐helicity of the peptides in a 30 mm sodium dodecyl sulfate solution was more closely correlated to hemolytic activity than antitumor activity.
Effects of lanthanide binding on the stability of de novo designed α‐helical coiled‐coils
Authors: KOHN WAYNE D. , KAY CYRIL M. , HODGES ROBERT S.
Published: August 2010

Effects of La3+ ion binding on the stability of de novo designed two‐stranded a‐helical coiled‐coils were studied. The coiled‐coils were composed of two 35‐residue polypeptide chains based on the „native” heptad sequence QgVaGbAcLdQeKf and each contained a Cys residue at position 2a to allow formation of an interchain disulfide bridge. The effect of LaCl3 on the stability of five analogs containing two or three Glu substitutions per chain at heptad positions e and g was observed by urea denaturation at 20°C. The analog E2(15,20), in which Glu residues are involved in interhelical i to i+ 5 repulsions, was stabilized relative to the control native peptide by addition of 50 mM LaCl3 to the buffer, whereas two analogs, in which Glu residues do not interact, were destabilized. These results suggest that LaCl3 may preferentially stabilize the folded state of E2(15,20) by the „bridging” of La3+ ions between two pairs of Glu residues usually involved in interhelical repulsions. Two analogs designed to contain two La3+ binding sites composed of three Glu residues each show greater stabilization by LaCl3 than E2(15,20) in the disulfide‐bridged form. The apparent stabilization of E2(15,20) by La3+ binding was not observed with either Ca2+ or Mg2+, indicating that the effect is specific for trivalent versus divalent cations.
A solution NMR study of the selectively 13C, 15N‐labeled peptaibol chrysospermin C in methanol
Authors: Anders R. , Wenschuh H. , Soskic V. , Fischer‐Frühholz S. , Ohlenschläger O. , Dornberger K. , Brown L.R.
Published: August 2010

Abstract: The conformation of the 19‐residue peptaibol chrysospermin C in methanol has been investigated by NMR spectroscopy using selective 15N and 13C labeling of the α‐aminoisobutyric acid (Aib) residues. Complete 1H and 13C sequential assignments, including stereospecific assignments for the heavily overlapped resonances from the two Cβ methyl groups of the eight Aib residues, are reported for a peptaibol for the first time. An Aib residue followed by a Pro is an exception to previous suggestions regarding stereospecific assignment of the two Cβ methyl groups of Aib residues. Local nuclear Overhauser effects and 3JHNC and 3JHNCβ scalar couplings indicate that the φ angles of the Aib residues are restricted sterically to local conformations consistent with right‐handed helices. Despite these constraints on the eight Aib residues, the NMR data for chrysospermin C in methanol are generally most consistent with an ensemble of transient conformations, including backbone conformations inconsistent with helical structures. Initial NMR measurements for chrysospermin C bound to micelles suggest structural and dynamic differences relative to alamethicin bound to micelles which may be related to differences in gating voltages for formation of ion channels.
The use of soluble synthetic peptide combinatorial libraries to determine antigen recognition of T cells
Authors: Hemmer B. , Pinilla C. , Appel J. , Pascal J. , Houghten R. , Martin R.
Published: August 2010

Abstract: T cells identify by their T‐cell receptor (TCR) short peptides in the context of major histocompatiblity complex (MHC) molecules. The interaction of the trimolecular complex composed of the TCR and MHC bound peptide was extensively studied using substitution analogs of the original peptide ligands to define those residues important for T‐cell recognition in the peptide chain. This approach has led to the observation that T‐cell recognition is highly flexible and that many different peptides can be recognized by an individual TCR. Others and we have recently introduced synthetic peptide combinatorial libraries (SCL) to investigate T‐cell recognition. Here we review the SCL‐based approaches and describe our current techniques for mapping TCR motifs for CD4+ T cells. The implications of our findings for the understanding of T‐cell recognition, as well as for future applications to study T‐cell responses in infectious diseases, autoimmune disorders and cancer are discussed.
Fmoc/Trt‐amino acids: comparison to Fmoc/tBu‐amino acids in peptide synthesis
Authors: BARLOS KLEOMENIS , GATOS DIMITRIOS , KOUTSOGIANNI SOFIA
Published: August 2010

Model peptides containing the nucleophilic amino acids Trp and Met have been synthesized with the application of Fmoc/Trt‐ and Fmoc/tBu‐amino acids, for comparison. The deprotection of the peptides synthesized using Fmoc/Trt‐amino acids in all cases leads to crude peptides of higher purity than that of the same peptides synthesized using Fmoc/tBu‐amino acids. © Munksgaard 1998.
Identification of the motilide pharmacophores using quantitative structure activity relationships
Authors: Khiat A. , Boulanger Y.
Published: August 2010

Erythromycin A and some derivatives have been shown to act as agonists at the motilin receptor site (motilides) and a structural similarity between these molecules and the N‐terminal fragment of motilin has been proposed. Conformational analysis and three‐dimensional quantitative structure‐activity relationship (3D‐QSAR) methods have been used to determine the homology between a series of erythromycin A derivatives and motilin 1‐10. A total of 18 compounds has been studied to correlate the gastrointestinal motor stimulating (GMS) activity with the structure‐related parameters determined by 3D‐QSAR. Two models with good predictive power of the GMS activity are presented, leading to the prediction of motilin 1‐10 activity. The models are consistent with the majority of the data available. The most significant parameters for GMS activity are a favorable dispersion interaction from the quaternary ammonium group of the desosamine ring. In motilin 1‐10, the aromatic side chains of Phe1 and Tyr7 seem to play the same role as the quaternary ammonium group in models 1 and 2, respectively. Some hydroxyl groups of erythromycin A derivatives and hydrophobic groups of the Val2 and lie4 side chains of motilin also contribute to the GMS activity. The experimental GMS activities measured are in good agreement with the predicted values, with correlation coefficient values of 0.98 and 0.94 in models 1 and 2, respectively.
Untersuchungen über den Stoff‐und Energies umsatz wachsender Schweine
Authors: Fingerling G. , Eisenkolbe P. , Hientzsch Br. , Just M. , Knauth G.
Published: August 2010

In der Kellnerschen Stärkewertlehre kommt der ”Wertig‐keit„ insofern eine große Bedeutung zu, als durch sie der Wirkungs‐wert eines Futtermittels in Prozenten des vollwertig gedachten zum Ausdruck gebracht wird. Um den Ansatzwert vollwertiger Futter‐mittel der Berechnung zugrunde legen zu können, hat O. Kellner den Fettansatz, den reine isolierte Nährstoffe bei der Mast aus‐gewachsener Ochsen bewirkten, durch Respirationsversuche ermittelt und mit Hilfe dieser Ansatzwerte und des Gehaltes der Futtermittel an verdaulichen Nährstoffen den Wirkungswert der vollwertig gedachten Futtermittel berechnet. Das Verhältnis des auf diese Weise berechneten zum tatsächlichen, im Versuch festgestellten Ansatzes nannte er Wertigkeit.

Auf dieselbe Weise haben wir bereits früher zu gleichem Zwecke das Fettansatzvermögen reiner Nährstoffe bei der Schweine‐mast ermittelt. Da unsere damaligen Versuche aber nur mit einem Tier und in einem Versuch durchgeführt werden konnten, wurde der Fettbildungswert von Erdnußöl durch diese Versuche auf breiterer Grundlage (6 Tiere) erneut festgestellt.

Bei diesen Versuchen fanden wir fast dieselben Werte, die wir früher erhalten hatten: 100 g verdauliches Erdnußöl bewirkten einen Fleisch‐ und Fettansatz von 862,1 Cal, entsprechend einem Ansatz von 90,7 g Korperfett, wahrend bei unserem früheren Ver suche ein Ansatz von 835,7 Cal, entsprechend 88,0 g Körperfett in Erscheinung getreten war.
Untersuchungen über den Nahrstoffgehalt von Baumwollsaatschrot
Authors: Kirsch W. , Jantzon H.
Published: August 2010

Die Prüfung eines Baumwollsaatschrotes der Firma Hobum, Vertriebsgesellschaft m. b. H., Harburg‐Wilhelmsburg, ergab auf Grund von Verdauungsversuchen an Hammeln folgenden Nährstoffgehalt: in 100 kg Baumwollsaatschrot mit 87,76% T.‐S, waren enthalten: 13,23 kg verdaulich.es Roheiweiß, 13.04 kg verdauliches Reineiweiß, 41.5 kg Stärkewert.
Fütterungsversuche mit ”Terno„ ‐Schnitten
Authors: Liebscher Wilhelm
Published: August 2010

Die nach dem Verfahren H. Fattinger hergestellten Ternoschnitte erwiesen sich als hochverdaulich. Durch den Zusatz von Satu‐rationsschlamm wird die Verdaulichkeit nicht beeinträchtigt. Nach eigenen Versuchen sowie nach Beobachtungen in der Praxis haben sie sich bei der Fütterung der Rinder, Pferde und Schweine gut bewährt.
Zum Einfluß der Ameisensäure auf den Säure‐Basen‐Haushalt
Authors: Lenkeit W. , Deppe K.
Published: August 2010

Unter dem Einfluß der zugeführten Menge Ameisensäure gehen die Basenwerte im Harn zurück. Es bleibt jedoch bis zum Ende der 5otägigen Versuchsfütterung ein Basenüberschuß bestehen.

Der Ammoniakgehalt des Harnes bleibt ziemlich unverändert mit einer geringen Tendenz zur Abnahme. Bei Mineralsäuresilagen war dagegen stets eine Zunahme festzustellen.

Die Alkalireserve des Blutes wird nach der Seite der Azidose verschoben.

Die Ca‐P‐Bilanz wird von der Ameisensäure in der zur Einsäuerung erforderlichen Menge nicht ungünstig beeinflußt. Mineralsäuresilagen haben eine entgegengesetzte Wirkung.