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Biomedical subjects

J Smit

Publications and source records attributed to J Smit.

At least 19 recordsLinked to original sources

Depot medroxyprogesterone versus norethisterone oenanthate for long-acting progestogenic contraception.

BACKGROUND: There are two injectable progestogen-only contraceptives (IPCs) that have been available in many countries in the world since 1983. They are both still extensively used in many developing countries, forming a large proportion of the health system's expenditure on contraception. These are depot medroxyprogesterone acetate (DMPA) and norethisterone oenanthate (NET-EN). These are both highly effective contraceptives that receive wide acceptance amongst women in their fertile years. They differ in frequency of administration that has implications on patient uptake. They also differ in cost that may significantly affect budgeting in the health system. A systematic comparison will aid to ensure their rational use. OBJECTIVES: To determine if there are differences between depot medroxyprogesterone acetate given at a dose of 150 mg IM every 3 months and norethisterone oenanthate given at a dose of 200mg IM every 2 months, in terms of contraceptive effectiveness, reversibility and discontinuation patterns, minor effects and major effects. SEARCH STRATEGY: We searched the computerized databases MEDLINE using PubMed, Popline, Cochrane Controlled Trials Register, Biblioline, LILACS, EMBASE and PASCAL for randomised controlled trials of DMPA versus NET-EN for long-acting progestogenic contraception. Studies were included regardless of language, and all databases were reviewed from the time that injectable progestogens have been in use. SELECTION CRITERIA: All randomised controlled comparisons of DMPA acetate given at a dose of 150 mg IM every 3 months versus NET-EN given at a dose of 200mg IM every 2 months, used for contraception, were included. Trials had to report on contraceptive efficiency and return to fertility, discontinuation risks and reasons for discontinuation, and clinical effects, both menstrual and non-menstrual. DATA COLLECTION AND ANALYSIS: BD and CM evaluated the titles and abstracts obtained through applying the search strategy and applied the eligibility criteria. BD attempted to contact authors where clarification of the data was required, and contacted all main manufacturers of the contraceptives. After inclusion of the two studies, the data was abstracted and analysed with RevMan 4.2. MAIN RESULTS: Two trials were included in this review. There was no significant difference between the two treatment groups for the frequency of discontinuation for either contraceptive, although the women on NET-EN were 4% more likely to discontinue for personal reasons than those on DPMA. Discontinuation because of accidental pregnancy did not differ between the groups. Although the duration of bleeding and spotting events was the same in each group, women on DPMA were 21% more likely to develop amenorrhoea. Mean changes in body weight at 12 and 24 months, and in systolic and diastolic blood pressure at 12 months did not differ significantly between the studies. AUTHORS' CONCLUSIONS: While the choice between DPMA and NET-EN as injectable progestogen contraceptives may vary between both health providers and patients, data from randomized controlled trials indicate little difference between the effects of these methods, except that women on DMPA are more likely to develop amenorrhoea. There is inadequate data to detect differences in some non-menstrual major and minor clinical effects.

Contraception↗

Mental health and sexual risk behaviours in a South African township: a community-based cross-sectional study.

OBJECTIVES: Despite the high prevalence of both mental illness and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) in developing countries, there are few data on the association between different forms of mental illness and sexual risk behaviours in resource-poor settings. The objective of this study was to examine the association between mental illness and HIV risk behaviours in a South African township. STUDY DESIGN: A cross-sectional study was performed among 645 individuals living in households selected at random. METHODS: A self-administered translated questionnaire investigated sexual risk behaviours [including sexual partners, condom use, casual sexual contacts, and sex in exchange for money, drugs or a place to stay (transactional sex)], depression (measured using the Center for Epidemiological Studies Depression Scale), alcohol abuse (from the Alcohol Use Disorders Identification Test), and post-traumatic stress disorder (based on the Life Event Checklist). RESULTS: Of the 645 individuals who completed the survey, 33% reported depression, 17% reported alcohol abuse, and 15% reported post-traumatic stress disorder. After adjusting for demographic characteristics, the presence of any of these three conditions was strongly associated with experiences of forced sex [adjusted odds ratio (AOR) 2.53; 95% confidence intervals (CI) 1.60-4.02], transactional sex (AOR 2.88; 95% CI 1.29-6.48) and increased condom use (AOR 2.07; 95% CI 1.32-3.25). CONCLUSIONS: These findings emphasize the substantial burden of mental illness in this setting, and its association with forced and transactional sex. The temporal nature of these associations is not always clear from this cross-sectional study, and additional prospective research is required. Public health interventions are needed to address the dual burden of HIV/AIDS and mental illness in this and similar settings.

Adolescent↗

Anti-tumor effects of the bacterium Caulobacter crescentus in murine tumor models.

Caulobacter crescentus is a gram negative, non-pathogenic bacterium, common in aquatic and soil environments. One feature of note is a protein surface layer (S-layer) composed of a single protein, organized as a self-assembled crystalline array that coats the bacterium. In the course of efforts to express cancer-associated peptides as genetic insertions into the S-layer, we noted a tumor suppressive effect of the unmodified bacterium. C. crescentus was examined for anti-tumor activity against three transplantable tumor mouse models: Lewis lung carcinoma cells transfected with the MUC1 gene in C57BL/6, murine mammary carcinoma (EMT-6) in BALB/c (both in prophylactic and therapeutic mode) and murine leukemia cells (L1210) in DBA2. Mice were immunized three times i.p. with C. crescentus (2 x 10(7) cells/mouse). In prophylactic mode, the mice were challenged with tumor cells two weeks after the last immunization. Immunization with live C. crescentus resulted in anti-tumor activity in all three transplantable tumor models, as measured by prolonged survival, reduced tumor mass or reduced number of lung nodules, compared to saline control groups. In the Lewis lung and the EMT-6 mammary carcinoma murine models the number of lung nodules as well as the tumor weight was lower in mice treated with C. crescentus, compared to the control group; for EMT-6, this was observed in prophylactic and therapeutic modes. In the murine leukemia and Lewis lung carcinoma models prolonged survival was observed in the groups of mice immunized with Caulobacters. In most cases the live C. crescentus cells were markedly more efficacious than heat killed or formalin fixed cells, despite the fact that they do not grow or persist in mice. The results suggest that C. crescentus may be a safe, bacterial immunomodulator for the treatment of tumors.

Animals↗

Sexual risk factors associated with volunteering for HIV vaccine research in South Africa.

There are few data on how the risk profiles of individuals who volunteer for HIV vaccine research compare to the general population from which participants are recruited. This study contrasts demographic and sexual risk behaviours among volunteers in an HIV vaccine preparedness cohort with data from a cross-sectional community survey conducted in the same peri-urban community during the same time period. For the HIV vaccine preparedness cohort, structured questionnaires were administered to 140 HIV-negative individuals aged between 16 and 40 years. A questionnaire with identical measures was self-administered in a cross-sectional community survey of 583 randomly selected individuals within the same age range. Compared to the local community sample, individuals who volunteered for the HIV vaccine preparedness cohort were younger (adjusted odds ratio = 0.48; 95% CI = 0.28-0.82), more likely to have had a sexually transmitted disease (adjusted odds ratio = 1.75; 95% CI = 1.03-2.99) and less likely to use condoms (adjusted odds ratio = 0.51; 95% CI = 0.3-0.86). Cohort participants were also more likely to perceive themselves and their partners to be at risk of HIV infection, though these associations did not persist in multivariate analysis. These findings suggest that volunteers for vaccine-related research may be at greater risk of HIV infection than the general population from which they are recruited.

AIDS Vaccines↗

Willingness to participate in HIV vaccine research in a peri-urban South African community.

Research on willingness to participate in HIV vaccine trials is important in preparations for HIV vaccine research, but there are few data from sub-Saharan Africa. We interviewed 198 individuals in a peri-urban South African community immediately after enrolment into an HIV vaccine preparedness study on their willingness to participate in hypothetical vaccine trials. Overall 23% of participants (n = 46) said that they would be willing to participate in an HIV vaccine trial. Willingness was associated with increasing age, male gender, and increasing knowledge about vaccines generally and HIV vaccines specifically. In multivariate analysis, a 1-unit increase in HIV vaccine knowledge score was associated with a 10-fold increase in willingness to participate (adjusted odds ratio, 10.72, 95% confidence intervals: 4.40-26.12). These results suggest that while willingness to participate in HIV vaccine trials is relatively low in this setting, educational campaigns may have a substantial impact on individuals' willingness to participate in research.

AIDS Vaccines↗

Influence of dentifrices and dietary components in saliva on wettability of pellicle-coated enamel in vitro and in vivo.

In vitro salivary pellicles were found to be less hydrophobic by water contact angles than clinically formed pellicles. In this study, water contact angles were measured on enamel coated with pellicles adsorbed from reconstituted human whole saliva (RHWS) and after exposure to dentifrices or dietary components. In addition, adhesion of Streptococcus oralis J22 to pellicles formed from RHWS with minor amounts of milk added and after exposure to dentifrices was studied. Exposure of RHWS-pellicles to milk or salad oil yielded an increase in the hydrophobicity of in vitro pellicles to values observed in vivo, but a decrease was seen after exposure to a sugar solution. Pellicles formed from saliva with 0.4% milk added attracted less S. oralis cells than pellicles formed in the absence of milk components. Exposure of pellicles formed from saliva with milk added to various dentifrices had a variable effect on bacterial adhesion: markedly lower numbers of adhering S. oralis were found for a dentifrice with NaF, but exposure to dentifrices containing SnF2 or hexametaphosphate showed slightly increased adhesion. In summary, dietary components have influence on the hydrophobicity of enamel pellicles, while combinations of dietary components and dentifrices certainly influence the adhesiveness of the pellicles. The effects of dietary components on pellicle conditioning film should be taken into consideration in research on the development of ingredients to control intraoral surface chemistry and microbiology, as well as in the development of oral products.

Animals↗

Furin and membrane type-1 metalloproteinase mRNA levels and activation of metalloproteinase-2 are associated with arterial remodeling.

Matrix metalloproteinase (MMP) activation is an essential feature of pathological and physiological arterial enlargement or shrinkage. Recently, furin-activated membrane type-1 MMP (MT1-MMP) was identified as the in vivo activator of MMP2 in mice. Although arterial enlargement and shrinkage are important in several pathological processes, this proprotein convertase-MT1-MMP axis has not been described during arterial remodeling. In rabbit femoral and carotid arteries, we report an increase in furin and MT1-MMP mRNA levels before and at the onset of arterial remodeling followed by an increase in activated MMP2. This reveals the presence of the proprotein convertase-MT1-MMP axis in flow-induced arterial remodeling and identifies furin as a possible target for local intervention in pathological arterial remodeling.

Animals↗

Counting the costs: comparing depot medroxyprogesterone acetate and norethisterone oenanthate utilisation patterns in South Africa.

BACKGROUND: In South Africa, where health care resources are limited, it is important to ensure that drugs provision and use is rational. The Essential Drug List includes depot medroxyprogesterone acetate (DMPA) and norethisterone oenanthate (NET-EN) as injectable progestagen-only contraceptives (IPCs), and both products are extensively used. OBJECTIVES AND METHODS: Utilisation patterns of the injectable contraceptive products DMPA and NET-EN are compared in the context of current knowledge of the safety and efficacy of these agents. Utilisation patterns were analysed by means of a Pareto (ABC) analysis of IPCs issued from 4 South African provincial pharmaceutical depots over 3 financial years. A case study from rural KwaZulu-Natal, South Africa, is used to examine utilisation patterns and self-reported side effects experienced by 187 women using IPCs. RESULTS: IPCs accounted for a substantial share of total state expenditure on drugs. While more DMPA than NET-EN was issued, NET-EN distribution from 2 depots increased over the 3-year period. Since DMPA was cheaper, if all NET-EN clients in the 1999/2000 financial year (annualised) had used DMPA, the 4 depots could have saved 4.95 million South African Rands on product acquisition costs alone. The KZN case study showed slightly more NET-EN (54%) than DMPA (46%) use; no significant differences in self-reported side effects; and that younger women were more likely to use NET-EN than DMPA (p = 0.0001). CONCLUSIONS: Providing IPCs on the basis of age is not appropriate or cost effective. Rational use of these products should include consideration of the cost of prescribing one over another.

Adolescent↗

Complete genome sequence of Caulobacter crescentus.

The complete genome sequence of Caulobacter crescentus was determined to be 4,016,942 base pairs in a single circular chromosome encoding 3,767 genes. This organism, which grows in a dilute aquatic environment, coordinates the cell division cycle and multiple cell differentiation events. With the annotated genome sequence, a full description of the genetic network that controls bacterial differentiation, cell growth, and cell cycle progression is within reach. Two-component signal transduction proteins are known to play a significant role in cell cycle progression. Genome analysis revealed that the C. crescentus genome encodes a significantly higher number of these signaling proteins (105) than any bacterial genome sequenced thus far. Another regulatory mechanism involved in cell cycle progression is DNA methylation. The occurrence of the recognition sequence for an essential DNA methylating enzyme that is required for cell cycle regulation is severely limited and shows a bias to intergenic regions. The genome contains multiple clusters of genes encoding proteins essential for survival in a nutrient poor habitat. Included are those involved in chemotaxis, outer membrane channel function, degradation of aromatic ring compounds, and the breakdown of plant-derived carbon sources, in addition to many extracytoplasmic function sigma factors, providing the organism with the ability to respond to a wide range of environmental fluctuations. C. crescentus is, to our knowledge, the first free-living alpha-class proteobacterium to be sequenced and will serve as a foundation for exploring the biology of this group of bacteria, which includes the obligate endosymbiont and human pathogen Rickettsia prowazekii, the plant pathogen Agrobacterium tumefaciens, and the bovine and human pathogen Brucella abortus.

Adaptation, Biological↗

Recombinant vaccines against infectious hematopoietic necrosis virus: production by the Caulobacter crescentus S-layer protein secretion system and evaluation in laboratory trials.

We report the development of an IHNV vaccine produced by a new protein production system based on the bacterium Caulobacter crescentus. The subunit vaccines that were tested contain a 184 amino acid segment of the IHNV glycoprotein in different fusion arrangements with the C. crescentus S-layer protein. Relative percent survival of 26 to 34% was demonstrated in rainbow trout fry for a vaccine that contained the 184 amino acid segment of the IHNV glycoprotein fused to the C-terminal one-quarter of the S-layer protein. Inclusion of the universal mammalian T-cell epitopes developed from the measles fusion protein or the tetanus toxin protein did not increase the effectiveness of the IHNV-G/S-layer recombinant protein.

Adjuvants, Immunologic↗

Expression and testing of Pseudomonas aeruginosa vaccine candidate proteins prepared with the Caulobacter crescentus S-layer protein expression system.

A novel bacterial protein secretion system was used to produce vaccine candidates against Pseudomonas aeruginosa. The surface protein (RsaA) of Caulobacter crescentus was adapted to produce recombinant vaccine proteins based on the pilus tip epitope ('adhesintope') of P. aeruginosa. Two versions of the adhesintope, with (PCK) or without (PE) the cysteine residues that flank the epitope were investigated, fused to the C-terminus or inserted into full-length RsaA. When expressed in caulobacter the fusion proteins were secreted as aggregates. Full length RsaA-containing adhesintopes assembled on the cell surface as an S-layer; these were recovered by low pH extraction. Vaccine candidates were evaluated in a mouse challenge model. PCK-containing proteins produced at least 1000-fold higher antibody titers against the adhesintope, compared to the PE version, exceeding titers achievable with any other vaccine preparation method. Immunoglobulin isotyping indicated a balanced IgG1/IgG2 response, though when challenged with P. aeruginosa, the PE- and PCK-containing proteins did not afford mice a significant level of protection. Overall, we describe a new system for vaccine production that shows promise as a fast, economical way to construct, evaluate and produce vaccine proteins.

Animals↗

Electric field induced desorption of bacteria from a conditioning film covered substratum.

Desorption of three oral bacterial strains from a salivary conditioning film on an indium tin oxide electrode during application of a positive (bacterial adhesion to the anode) or a negative electric current was studied in a parallel plate flow chamber. Bacterial adhesion was from a flowing suspension of high ionic strength, after which the bacterial suspension was replaced by a low ionic strength solution without bacteria and currents ranging from -800 to +800 microA were applied. Streptococcus oralis J22 desorbed during application of a positive and negative electric current with a desorption probability that increased with increasing electric current. Two actinomyces strains, however, could not be stimulated to desorb by the electric currents applied. The desorption forces acting on adhering bacteria are electroosmotic in origin and working parallel to the electrode surface in case of a positive current, whereas they are electrophoretic and electrostatic in origin and working perpendicular to the surface in case of a negative current. By comparison of the effect of positive and negative electric currents, it can be concluded that parallel forces are more effective in stimulating bacterial desorption than perpendicular forces. The results of this study point to a new pathway of cleaning industrial and biomedical surfaces without the use of detergents or biocides.

Actinomyces↗

Development of small high-copy-number plasmid vectors for gene expression in Caulobacter crescentus.

Caulobacter crescentus is a bacterium with a distinctive life cycle and so it is studied as a cell development model. In addition, we have adapted this bacterium for recombinant protein production and display based on the crystalline surface protein (S)-layer and its C-terminal secretion signal. We report here the development of small, high-copy-number plasmid vectors and methods for producing an obligate expression host. The vectors are based on a narrow-host-range colE1-replicon-based plasmid commonly used in Escherichia coli, to which was added the replication origin of the IncQ plasmid RSF1010. C. crescentus strains were modified to enable plasmid replication by introduction of the RSF1010 repBAC genes at the recA locus. The small (4.0-4.5 kb) plasmids were in high copy numbers in both C. crescentus and E. coli and amenable to rapid methods for plasmid isolation and DNA sequencing. The method for introducing repBAC is suitable for other C. crescentus strains or any bacterium with an adequately homologous recA gene. Application of the vector for protein expression, based on the type I secretion system of the S-layer protein, when compared to constructs in broad-host-range plasmids, resulted in reduced time and steps required from clone construction to recombinant protein recovery and increased protein yield.

Bacterial Proteins↗

Temporary discontinuation: a compliance issue in injectable users.

This study examined compliance in injectable users and followed women post-discontinuation to document their contraceptive practices. A cohort of 189 predominantly new users of depot-medroxyprogesterone acetate and norethisterone oenanthate were recruited and followed for 2 years regardless of whether or not they continued the method. Continuation rates were 42% at 1 year and 21% at 2 years. Of the 78 women who discontinued the method, 31 reported that they were "taking a break." For 20 of these women, this break (nonuse segment) occurred within the 2-year period, and 15 of them returned to the injection before the end of study period. The other five switched methods after the nonuse segment. The mean length of the nonuse segment was 7 months (range 2-13 months). In all 20 women, no other contraceptive method was used, they remained sexually active, and started the break within 6 months of commencing use of the injectable. In addition, 11 women were in a self-reported nonuse segment at the end of the study and stated their intention to return to the method at a later date. Menstrual disturbances were cited as the main reason for the break. Strengthened counseling at method acceptance was identified as a strategy to decrease the frequency of breaks in injectable method use.

Adult↗

Emergency contraception in South Africa: knowledge, attitudes, and use among public sector primary healthcare clients.

To determine knowledge of, attitudes toward, and use of emergency contraception (EC), interviews were held with 1068 clients of 89 public sector primary healthcare facilities in two urban and two rural areas of South Africa. Only 22.8% of the clients had heard of EC. Awareness was significantly lower in the most rural area and among older, less educated women. Knowledge of EC was superficial, with 47.1% unsure of the appropriate interval between unprotected intercourse and starting EC and 56.6% not knowing whether it was available at the clinic. Few (9.1%) of those who knew of EC had used it. After explaining EC, attitudes toward its use were found to be positive, with 90.3% indicating that they would use it if needed. Awareness was lower than in developed countries, but higher than in other developing countries. Findings indicate that if women know of EC, where to get it, and how soon to take it, they would use it if needed.

Adolescent↗

Uptake of pp65 in in vitro generated pp65-positive polymorphonuclear cells mediated by phagocytosis and cell fusion?

OBJECTIVE: The cytomegalovirus (CMV) antigenemia consists of the detection of CMV pp65 in the nucleus of polymorphonuclear granulocytes (PMN), but it is unclear where and how PMN pick up virus particles or proteins. In an in vitro model for CMV antigenemia we investigated the mechanism of pp65 uptake by PMN that results in its expression in the nucleus. METHODS: A series of inhibitors of different mechanisms was used to study the uptake of pp65 by PMN during coculture with CMV-infected endothelial cells and we performed a morphological analysis by light and transmission electron microscopy. RESULTS: Nocodazole and cytochalasin B inhibited uptake of pp65 by PMN with 59.4 +/- 14.1 and 73.3 +/- 12.7%, respectively. The presence of anti-CMV hyperimmune globulin or lactoferrin during coculture reduced the number of pp65-positive PMN with 45.8 +/- 7.0 or 40.6 +/- 3.2%. Furthermore, a small number of the pp65-positive PMN obtained after coculture had fused to large cells with multilobed nuclei. PMN were observed that enclosed viral particles as well as free viral particles containing PMN in the cytoplasm. CONCLUSION: Fusion of viral particles with PMN and phagocytosis are both involved in the uptake of pp65.

Antibodies, Viral↗

How the body contributes to the wake in undulatory fish swimming: flow fields of a swimming eel (Anguilla anguilla).

Undulatory swimmers generate thrust by passing a transverse wave down their body. Thrust is generated not just at the tail, but also to a varying degree by the body, depending on the fish's morphology and swimming movements. To examine the mechanisms by which the body in particular contributes to thrust production, we chose eels, which have no pronounced tail fin and hence are thought to generate all their thrust with their body. We investigated the interaction between body movements and the flow around swimming eels using two-dimensional particle image velocimetry. Maximum flow velocities adjacent to the eel's body increase almost linearly from head to tail, suggesting that eels generate thrust continuously along their body. The wake behind eels swimming at 1.5 Ls(-1), where L is body length, consisted of a double row of double vortices with little backward momentum. The eel sheds two vortices per half tail-beat, which can be identified by their shedding dynamics as a start-stop vortex of the tail and a vortex shed when the body-generated flows reach the 'trailing edge' and cause separation. Two consecutively shed ipsilateral body and tail vortices combine to form a vortex pair that moves away from the mean path of motion. This wake shape resembles flow patterns described previously for a propulsive mode in which neither swimming efficiency nor thrust is maximised but sideways forces are high. This swimming mode is suited to high manoeuvrability. Earlier recordings show that eels also generate a wake reflective of maximum swimming efficiency. The combined findings suggest that eels can modify their body wave to generate wakes that reflect their propulsive mode.

Anguilla↗

Secretion of the Caulobacter crescentus S-layer protein: further localization of the C-terminal secretion signal and its use for secretion of recombinant proteins.

The secretion signal of the Caulobacter crescentus S-layer protein (RsaA) was localized to the C-terminal 82 amino acids of the molecule. Protein yield studies showed that 336 or 242 C-terminal residues of RsaA mediated secretion of >50 mg of a cellulase passenger protein per liter to the culture fluids.

Bacterial Outer Membrane Proteins↗