Antimicrobial resistance trends of shigellae isolates from Calabar, Nigeria.

During a 3-year study (January 1986-December 1988), stools of 2200 diarrhoeal or dysenteric patients were examined by culturing and 108 (4.9%) were found positive for shigellae. Shigella flexneri was the commonest species isolated (54.6%), followed by Sh. dysenteriae (24.1%). Patients aged less than or equal to 15 years accounted for 51.4% of cases. Shigellae over the 3 years showed high and sometimes rising resistance to ampicillin, chloramphenicol, streptomycin and cotrimoxazole and complete resistance to tetracyclines and sulphonamides. Sh. sonnei strains isolated in 1986 and 1987 were almost invariably sensitive to all antimicrobial agents except ampicillin, while in 1988 strains were resistant to all. The isolation rate was higher (74.1%) during the dry season than in the rainy season (25.9%) (P less than 0.01). Low standards of community and personal hygiene and improper sewage disposal are the prevailing epidemiological factors identified.     

Expandable intraluminal graft: a preliminary study. Work in progress

To overcome the problem of recurrence of stenosis after vascular balloon dilatations, we developed an expandable, intraluminal graft that allows dilatation of the lesion and simultaneous placement of a supportive endoprosthesis to prevent recoil of the arterial wall. The graft is made of continuous, woven, stainless steel wire. The resulting tubular mesh has a wall thickness of 200-450 micron and 80% open surface. The grafts, mounted on angioplasty catheters, are introduced through 8-12-F Teflon sheaths. Eleven grafts of 6, 8, and 10 mm in diameter by 20 mm long were placed in the aorta, common carotid, superior mesenteric, iliac, and renal arteries of dogs. Six grafts showed no stenosis in follow-up studies of up to 8 weeks. Two grafts had moderate stenosis as a result of neointimal hyperplasia. Two partial and one complete graft thrombosis occurred in nonheparinized animals in which the graft outflow was restricted. Anticoagulant was not used on a long-term basis. Light and electron microscopy studies showed complete covering of the graft's inner surface by endothelium at 3 weeks.     

Impact of diabetes mellitus on driving safety

Driving ability is controlled by specific regulations. Therefore disabled individuals or those with certain chronic diseases may be affected by these regulations. These latter are based on assumption that the existence and the nature of certain diseases may cause particular hazard; and this could be prevented by introducing certain driving regulations. This hypothesis has not been tested properly, considering the proposed and suspected risk factors. Diabetes mellitus is a good example of the interested medical condition in this field. Review of the literature do not provide adequate information to allow us to conclude whether the insulin treated diabetic person is at higher risk to develop traffic accident, compared with non diabetic individual; and there is no definite explanation whether hypoglycaemia play a causative role in the etiology of traffic accident among insulin treated diabetics. Perhaps the lack of knowledge in this field is due to use of non-standardized methodologies and small sample size studies which make the comparisons difficult. The existing regulations in different countries are based on empirical knowledge and common sense. This often leads to conflictual situations and apparently discriminatory decisions regarding diabetics. Further comparative and prospective studies are needed.     

Evaluation of the protective efficacy of Vibrio cholerae ghost (VCG) candidate vaccines in rabbits

An effective Vibrio cholerae vaccine is needed to reduce the morbidity and mortality caused by this pathogen. Despite the availability of current oral vaccines with measurable efficacy, there is need for more effective vaccines with broad-spectrum efficacy in target populations. Recent studies have shown that bacterial ghosts, produced by the expression of cloned lysis gene E, possess adjuvant properties and are immunogenic. In this study, ghosts were prepared from V. cholerae O1 or O139 and evaluated as vaccines in the reversible intestinal tie adult rabbit diarrhea (RITARD) model. Rabbits were orally immunized with different doses of V. cholerae ghost (VCG) formulations. The vaccine formulations elicited high levels of serum vibriocidal titers against indicator strains. The magnitude of the response was measured as the geometric mean titer (GMT) increase for all rabbits in relation to prevaccination titers. The induction of cross protection was evidenced by the ability of serum from VCG-immunized rabbits to mediate complement-dependent killing of both the homologous and the heterologous strains. Immunized rabbits were protected against intraduodenal challenge 30 days after primary immunization. Protective immunity against challenge appeared to be dose dependent and was associated with marked inhibition of colonization. These results indicate that VCGs represent a novel approach to cholera vaccine development and constitute an effective vaccine delivery vehicle.     

Recombinant Vibrio cholerae ghosts as a delivery vehicle for vaccinating against Chlamydia trachomatis

An efficacious vaccine is needed to control the morbidity and burden of rising healthcare costs associated with genital Chlamydia trachomatis infection. Despite considerable efforts, the development of reliable chlamydial vaccines using conventional strategies has proven to be elusive. The 40kDa major outer membrane protein (MOMP) of C. trachomatis is so far the most promising candidate for a subunit vaccine. The lack of satisfactory protective immunity with MOMP-based vaccine regimens to date would suggest that either MOMP alone is inadequate as a vaccine candidate or better delivery systems are needed to optimize the effect of MOMP. Recombinant Vibrio cholerae ghosts (rVCG) are attractive for use as non-living vaccines because they possess strong adjuvant properties and are excellent vehicles for delivery of antigens of vaccine relevance to mucosal sites. The suitability of the ghost technology for designing an anti-chlamydial vaccine was evaluated by constructing a rVCG vector-based candidate vaccine expressing MOMP (rVCG-MOMP) and assessing vaccine efficacy in a murine model of C. trachomatis genital infection. Intramuscular delivery of the rVCG-MOMP vaccine induced elevated local genital mucosal as well as systemic Th1 responses. In addition, immune T cells from immunized mice could transfer partial protection against a C. trachomatis genital challenge to nai;ve mice. These results suggest that rVCG expressing chlamydial proteins may constitute a suitable subunit vaccine for inducing an efficient mucosal T cell response that protects against C. trachomatis infection. Altogether, the potency and relatively low production cost of rVCG offer a significant technical advantage as a chlamydial vaccine.     

Bacterial ghosts as carrier and targeting systems for mucosal antigen delivery

The application of new strategies to develop effective vaccines is essential in modern medicine. The bacterial ghost system is a novel vaccine delivery system endowed with intrinsic adjuvant properties. Bacterial ghosts are nonliving gram-negative bacterial cell envelopes devoid of cytoplasmic contents while maintaining their cellular morphology and native surface antigenic structures including bioadhesive properties. They are produced by PhiX174 protein E-mediated lysis of gram-negative bacteria. The intrinsic adjuvant properties of bacterial ghost preparations enhance immune responses against envelope-bound antigens, including T-cell activation and mucosal immunity. Since native and foreign antigens can be expressed in the envelope complex of ghosts before E-mediated lysis, multiple antigens of various origin can be presented to the immune system simultaneously. In addition, the extended bacterial ghost system represents a platform technology for specific targeting of DNA-encoded antigens to primary antigen-presenting cells. The potency, safety and relatively low production cost of bacterial ghosts offer a significant technical advantage, especially when used as combination vaccines.     

Outcomes of pharmaceutical care intervention to hypertensive patients in a Nigerian community pharmacy

Objective To describe pharmaceutical care interventions provided to hypertensive patients in a Nigerian community pharmacy setting, and to assess the impact of the practice on selected patient outcomes. Method A non‐randomised, single‐site study was conducted using community‐dwelling patients with hypertension. A pharmaceutical care intervention, which consisted mainly of verbal counselling, provision of an information leaflet, and subsequent monitoring with reinforcement, was provided. Parameters assessed at baseline and end of investigation included blood pressure control, body mass index determination, level of medication adherence, patient knowledge of the disease, and patient satisfaction. Key findings Forty‐two (42) patients were recruited and 36 completed the study, 26 (73%) were males, and 33 (92%) were married. Twenty (20, 58%) had post‐secondary education. About three‐quarters (27, 81%) were either overweight or obese (BMI >25). There was a significant difference between mean systolic blood pressure at baseline (187.67 ± 29.46 mmHg) and at the end of the study (137.22 ± 21.65 mmHg), P< 0.0001. Changes in mean diastolic blood pressure at baseline (117.56 ± 21.65) and end of study (89 ± 17.23), were also significant (P< 0.0001). Some 27 (75%) reached systolic blood pressure goals while 25 (69%) attained diastolic blood pressure goals. Prior to the pharmaceutical care intervention, 27 (75%) were not aware that salt intake was a risk factor in hypertension, and a similar proportion thought that hypertension was curable. The pharmaceutical care intervention produced a significantly higher patient‐reported satisfaction rating than baseline: 3.48 ± 0.83 (49%) versus 3.92 ± 0.62 (74%); t = 2.548; P=0.013 and 3.30 ± 0.72 (41%) versus 4.27 ± 0.56 (87%); t= 6.381, P< 0.0001 on the subscales respectively. Conclusion Pharmaceutical care provided to hypertensive patients in a Nigerian community pharmacy setting improved blood pressure control and overall patient satisfaction with pharmaceutical services.     

Chukranoids A–I,isopimarane diterpenoids from Chukrasia velutina

Journal of Natural Medicines - Bioactivity guided separation of Chukrasia velutina root methanolic extract led to the isolation of nine new isopimarane diterpenoids, chukranoids A–I...     

Computationally-assisted discovery and structure elucidation of natural products

Computer hardware development coupled with the development of quantum chemistry, new computational models and algorithms, and user-friendly interfaces have lowered the barriers to the use of computation in the discovery and structure elucidation of natural products. Consequently, the use of computational chemistry software as a tool to discover and determine the structure of natural products has become more common in recent years. In this review, we provide several examples of recent studies that used computer technology to facilitate the discovery and structure determination of various natural products.