Modifications of the hydrophilicity of heterocyclic methacrylate copolymers for protein release

A series of copolymers comprising ethyl methacrylate (EM) and tetrahydrofurfuryl methacrylate (THFMA) gelled with either THFMA monomer or hydroxyethyl methacrylate (HEMA) monomer have been developed. In this paper, we examine the water uptake characteristics of the polymer systems and address the possibility of increasing the hydrophilicity of the systems by changing the ratios of the copolymers. We have investigated whether protein release from the polymers is related to the composition of the polymer systems. More protein was released from the polymers gelled with the more hydrophilic monomer (HEMA) than with THFMA. This was consistent with the calculated diffusion coefficients, which were 10 times greater for the polymers gelled with HEMA than those gelled with THFMA. Interestingly, the water uptake and protein release profiles were not dependent on the ratio of EM and THFMA in the copolymers. This is probably due to the conflicting roles of THFMA in the copolymer; it is both the more hydrophilic component as well as a cross-linking agent. In addition, it would appear that the structural and surface topography of these polymers had more significant effects on protein release than copolymer composition.     

Female genital schistosomiasis as an evidence of a neglected cause for reproductive ill-health: a retrospective histopathological study from Tanzania

Background  

Schistosomiasis affects the reproductive health of women. Described sequelae are ectopic pregnancy, infertility, abortion, and cervical lesions and symptoms mimicking cervical cancer and STIs. There are indications that cervical schistosomiasis lesions could become co-factors for viral infection such as HIV and HPV.     

Improvement in glucose tolerance after one year of follow-up in a Hindu community in Africa

Oral glucose tolerance was studied following a 75 g glucose load in 108 (82.4%) of 131 male and 110 (79.1%) of 139 female members of a Hindu subcommunity aged 15 years and over in Dar es Salaam. One year later, the glucose tolerance tests were repeated in 93 (86.1%) and 93 (84.5%) of the 108 male, and 110 of the female subjects, respectively. In the first survey, 25 (26.9%) of the 93 male and 24 (25.8%) of the 93 female subjects had impaired glucose tolerance (IGT), 6 (6.4%) and 15 (16.1%), respectively, had diabetes mellitus; and 62 (66.7%) and 54 (58.1%), respectively, had normal glucose tolerance. In the repeat survey, of the 93 male and 93 female subjects, 8 (8.6%) and 7 (7.5%) had IGT, 4 (4.3%) and 10 (10.8%) had diabetes; and 81 (87.1%) and 76 (81.7%) were normal, respectively. Of the 21 subjects diagnosed as having diabetes in the first survey, 13 (61.9%) continued to show diabetic glucose tolerance; 4 (19%) IGT and 4 (19%) had normal glucose tolerance with no gender difference. One (1.6%) of the 62 male subjects and none of the 54 females with normal glucose tolerance in the first survey progressed to IGT, while the remainder retained normal glucose tolerance. Diabetes and IGT rates in both surveys were higher for the older than the younger persons. A significant fall in mean fasting and post-75 g blood glucose levels, and in mean systolic and diastolic pressure levels was observed between the first and second surveys in both genders. There was, however, no significant difference in body mass index (BMI), serum total cholesterol and triglyceride levels between surveys, suggesting that major dietary changes had not taken place. Male subjects who showed persistent IGT had significantly lower mean level of body mass index (kg/m²) than subjects who reverted to normal, whilst for the whole group those who had persistent IGT were older. It is tempting to speculate that these changes were due to community action. However, in view of the lack of change in weight and lipids and similar results in other communities in Tanzania when retested at 1 week, further studies are needed to establish the significance of the findings.     

A study of the use of maternity and child welfare clinics in case-finding for pulmonary tuberculosis in Kenya

This investigation is the seventh in a series of case-finding studies in Kenya. It explores the potential value of questioning mothers attending maternity and child welfare (M & CW) clinics to identify tuberculosis suspects (individuals aged 6 years or more with a cough for 1 month or more or hemoptysis) living in their households. The study was carried out in all the eight M & CW clinics in two divisions (populations 86,000 and 112,000) of two different districts. The mothers were asked to give a standard letter, which explained the possible importance of a chronic cough, to each suspect they identified and invited the suspect to attend the district hospital chest clinic. Each suspect attending the clinic was entered in a special register and two sputum specimens were collected. For those who failed to attend, the specimens were collected at a home visit. Of the total of 342 suspects living in the two study areas who were registered at the M & CW clinics during 1 year, 261 were identified by the mothers but 19 denied having received the standard letter. The remaining 81 had not been identified by mothers but had attended the M & CW clinics on their own initiative. Of the 242 suspects who received the letter, 89 (39%) attended the hospital chest clinic, 74% within a week of the letter being issued from the M & CW clinic. The main reasons given for not attending the hospital chest clinic by the remaining suspects were financial or because their cough had improved or disappeared. Sputum was collected from 238 suspects and examined bacteriologically: in six (2.5%) it was positive for tubercle bacilli on smear and culture and in a further two (0.8%) the sputum was positive on culture only. Of those attending the hospital chest clinic 2.9% were smear- and culture-positive and 4.7% were culture positive. This method of case-finding has yielded disappointing results, for only 4% of the estimated annual incidence of smear-positive cases was detected.     

Expandable metallic stent for the treatment of left-sided colonic obstruction with malignant disease

Recently, it was reported that an EMS (expandable metallic stent) was useful for treatment of colorectal obstruction. In our department, EMSs were used for seven patients with left-sided colonic obstruction with unresectable malignant disease. After these treatments with EMS, their symptoms were improved and they were able to intake food. Stomal formation was avoided except in one patient with severe soiling. In conclusion, EMS is thought to be useful for the improvement of quality of life in the patients with unresectable malignant colonic obstruction.     

A polymeric system for the intra-oral delivery of an anti-fungal agent

Oral candidal infections are often persistent and intractable and thus the aim of this study was to develop a polymeric sustained release device to improve the topical treatment of these infections. A self curing system based on poly(ethyl methacrylate) and tetrahydrofurfuryl methacrylate (PEM/THFM) was used with chlorhexidine diacetate (CX) added at levels between 0 and 12% w/w. Water uptake by the device was assessed gravimetrically and CX release measured by UV spectrometry. Anti candidal activity was established by culturing azole sensitive and resistant strains of Candida albicans in the presence of the polymeric delivery device with and without CX. Candidal growth was measured by turbidimetry or surviving colony-forming unit (CFU) formation. There was an initial high release of CX over 24 h followed by a slow diffusion up to 7 days. CX inhibited candidal growth and survival markedly in vitro, with the test samples showing less than 0.5 x 10(-7) CFU/ml compared to controls (3-4 x 10(-7) CFU/ml). These results indicate the potential of a chlorhexidine containing PEM/THFM polymeric system in the treatment of persistent candidal infections.     

Effects of protein binding on the biodistribution of PEGylated PLGA nanoparticles post oral administration

The surface of nanoparticles is often functionalised with polymeric surfactants, in order to increase systemic circulation time. This has been investigated mainly for intravenously administered nanoparticles. This study aims to elucidate the effect of surface coating with various concentrations of polymeric surfactants (PEG and Pluronics F127) on the in vitro protein binding as well as the tissue biodistribution, post oral administration, of PLGA nanoparticles. The in vitro protein binding varied depending on the polymeric surfactant used. However, in vivo, 1% PEG and 1% Pluronics F127 coated particles presented similar biodistribution profiles in various tissues over seven days. Furthermore, the percentage of PEG and Pluronics coated particles detected in plasma was higher than that of uncoated PLGA particles, indicating that systemic circulation time can also be increased with oral formulations. The difference in the in vitro protein binding as a result of the different poloxamers used versus similar in vivo profiles of these particles indicates that in vitro observations for nanoparticles cannot represent or be correlated to the in vivo behaviour of the nanoparticles. Our results therefore suggest that more studies have to be conducted for oral formulations to give a better understanding of the kinetics of the particles.     

Tuberculosis in diabetic patients in Tanzania

During a 1-7 year follow-up of 1250 African diabetic patients at Muhimbili Medical Centre, Dar es Salaam, 68 (5.4%) were known to have developed pulmonary tuberculosis and two (0.2%) spinal tuberculosis. In 18 (25.7%) of the 70 patients tuberculosis was diagnosed prior to the diagnosis of diabetes, and in 32 (45.7%) after the diagnosis of diabetes. In 20 (28.6%) patients tuberculosis and diabetes were diagnosed at approximately the same time with most presenting with symptoms of diabetes. The prevalence of tuberculosis was greater in the young, in those with a low body mass index (BMI), in patients with insulin-dependent diabetes mellitus compared to those with non-insulin-dependent diabetes mellitus (9.0% vs 2.7%) and in those whose diabetes was poorly controlled. Seventeen (24.3%) of the 70 patients are known to have died. Pulmonary tuberculosis may progress rapidly and a high index of suspicion is required. It remains a significant cause of morbidity and mortality among diabetic patients in developing countries.