Effect of functional excipients on the dissolution and membrane permeation of furosemide formulated into multiple-unit pellet system (MUPS) tablets.

The effect of functional excipients (i.e. chitosan, sodium lauryl sulphate, NaHCO3, and CaCO3) formulated in multiple-unit pellet system (MUPS) tablets has been investigated on the dissolution and permeability of furosemide, a BCS class IV compound. Spherical beads were produced and compressed into MUPS tablets. MUPS tablet formulations were evaluated for hardness, disintegration, mass variation, friability, and dissolution (pH 1.2, pH 4.6, and pH 7.4). Ex vivo permeability studies were conducted across excised pig tissues (pyloric antrum and duodenal region) on selected experimental MUPS tablet formulations. Histological analysis was conducted on the tissues after exposure to selected experimental MUPS tablet formulations. Dissolution results in the 0.1 M HCl (pH 1.2) showed the highest effect of the excipients on furosemide release. Dissolution parameters showed increased dissolution of furosemide for the MUPS tablet formulations containing functional excipients: a 4.5-10-fold increase in the AUC values, the %max showed a 60-70% increase and up to a 19-fold increase in DRi was seen. Permeability results revealed a 2.5-fold higher cumulative percentage transport for selected formulations. The results proved that functional excipients incorporated into beads, compressed into MUPS tablet formulations increased furosemide release as well as permeation across excised intestinal tissues.

The spectrum of orofacial clefts and treatment logistics at Universitas Academic Hospital, Bloemfontein, South Africa.

BACKGROUND: Cleft lips and/or palates should be identified early and be operated on at specific ages according to international recommendations. In African countries, however, cleft lip and palate surgeries are often delayed. METHODS: A retrospective, descriptive study was done to determine the distribution, specific time delays, demographics and loss to follow-up of patients with cleft lip and/or palates treated at Universitas Academic Hospital over a 10-year period. Data was obtained from outpatient files from the Plastic and Reconstructive Surgery Department at Universitas Academic Hospital. Two hundred and three of 318 records (63.8%) had the defined variables documented. RESULTS: The median time from first presentation to specialist consultation was 1.9 months. The median ages for first presentation was 2.2 months and for specialist consultation 5.2 months. Patients mainly had isolated cleft palates (42.4%), followed by both cleft lip and palate (31%) and isolated cleft lips (24.6%). A quarter of patients (25.6%) were lost to follow-up. More than a third (36.5%) of patients were referred from the local Motheo district and 12.8% were referred from Lesotho. CONCLUSION: In our setting, patients with cleft lip and/or palate are generally diagnosed and referred late. These patients also have delayed access to specialist consultation. Often patients are only evaluated by specialists at ages whereby they should have already undergone their first surgeries. Too many patients are lost to follow-up.

Yield and Metabolite Production of Pelargonium sidoides DC. in Response to Irrigation and Nitrogen Management.

Competition for water between agricultural and non-agricultural economic sectors hampers agricultural production, especially in water-scarce regions. Understanding crop responses in terms of yield and quality to irrigation is an important factor in designing appropriate irrigation management for optimal crop production and quality. Pelargonium sidoides DC., often harvested from the wild, is in high demand in the informal market and for commercial formulations. Agricultural production of high-quality materials through cultivation can help reduce pressure on its wild populations. This study aimed at determining the effects of water and nitrogen on P. sidoides yield and metabolite production. The irrigation treatments applied were 30%, 50%, and 70% of an allowable depletion level (ADL), while the nitrogen (N) levels were 0 (control), 50, 100, and 150 kg ha-1. The 30% ADL resulted in a significantly higher biomass and root yield. Nitrogen at 50 and 100 kg ha-1 resulted in a significantly higher biomass yield, compared to the N control. An increase in sugars and citrate cycle components was observed for the well-watered 30% ADL treatment, whereas water-stressed (50% and 70% ADL) treatments increased alanine, aspartate, and glutamate metabolism, increasing levels of asparagine, 4-aminobutyrate, and arginine. The treatments had no significant effect on the root content of esculin, scopoletin, and umckalin. Water stress induced metabolite synthesis to mitigate the stress condition, whereas under no water stress primary metabolites were synthesized. Moreover, cultivation of P. sidoides as a conservation strategy can increase yield without affecting its bioactivity, while providing sustenance for the rural communities.

Preoperative fasting times: Prescribed and actual fasting times at Universitas Hospital Annex, Bloemfontein, South Africa.

BACKGROUND: Guidelines recommend a preoperative fasting period of 6 hours for solid food and 2 hours for clear fluids. Because of fixed meal times and imprecise operation starting times, patients often fast for an extended period of time. OBJECTIVE: To investigate the prescribed preoperative fasting times, and the actual duration of fasting, compared with the internationally accepted fasting times for solid food and clear fluids. METHODS: Patients (N=105) aged 14 - 60 years, who were scheduled for elective surgery in the morning session (list starting time 07h00), were included in this prospective study. On arrival in theatre, all patients were asked when they last ate and drank. Anaesthetic records were used to determine the prescribed fasting times and operation starting times. RESULTS: For solids, patients were most frequently prescribed to start fasting from 22h00 to 00h00 (53.3% and 39.1%, respectively). No patient fasted <8 hours. The median duration of fasting was 14 hours and 45 minutes (range 9 hours and 45 minutes - 19 hours and 5 minutes). For fluids, patients were most frequently prescribed to start fasting from 05h00 (46.7%), 00h00 (27.6%) and 22h00 (7.6%). In practice, no patient ingested fluids after 22h30 or <9 hours preoperatively. The median fasting time for oral fluids was 13 hours and 25 minutes (range 9 hours and 37 minutes - 19 hours and 5 minutes). CONCLUSION: Most patients started fasting too early preoperatively, consequently withholding food and oral fluids for longer than recommended. An increased awareness regarding complications of unnecessarily long fasting times, and interventions to correct this problem, is required.

Preoperative fasting times: Prescribed and actual fasting times at Universitas Hospital Annex, Bloemfontein, South Africa

Background. Guidelines recommend a preoperative fasting period of 6 hours for solid food and 2 hours for clear fluids. Because of fixed meal times and imprecise operation starting times, patients often fast for an extended period of time.Objective. To investigate the prescribed preoperative fasting times, and the actual duration of fasting, compared with the internationally accepted fasting times for solid food and clear fluids.Methods. Patients (N=105) aged 14 - 60 years, who were scheduled for elective surgery in the morning session (list starting time 07h00), were included in this prospective study. On arrival in theatre, all patients were asked when they last ate and drank. Anaesthetic records were used to determine the prescribed fasting times and operation starting times. Results. For solids, patients were most frequently prescribed to start fasting from 22h00 to 00h00 (53.3% and 39.1%, respectively). No patient fasted <8 hours. The median duration of fasting was 14 hours and 45 minutes (range 9 hours and 45 minutes - 19 hours and 5 minutes). For fluids, patients were most frequently prescribed to start fasting from 05h00 (46.7%), 00h00 (27.6%) and 22h00 (7.6%). In practice, no patient ingested fluids after 22h30 or <9 hours preoperatively. The median fasting time for oral fluids was 13 hours and 25 minutes (range 9 hours and 37 minutes - 19 hours and 5 minutes).Conclusion. Most patients started fasting too early preoperatively, consequently withholding food and oral fluids for longer than recommended. An increased awareness regarding complications of unnecessarily long fasting times, and interventions to correct this problem, is required

Screening of tea (Camellia sinensis) for trait-associated molecular markers.

This study was done to identify random amplified polymorphic DNA (RAPD) markers that may associate with seven important traits in tea. Sixty RAPD primers were first screened using 18 cultivars under each of the 7 traits, followed by confirmatory screening of 20 promising primers with 32 tea cultivars. Six RAPD primers generated a total of nine specific bands that associated with six desired traits: black tea quality and tolerance to drought, high temperature, low temperature, Phomopsis theae, and high yield. These markers would allow early identification of plant material with the desired traits that can be advanced to the next stage of selection and enhance targeted choice of breeding stocks with the desirable traits. The nine RAPD markers identified in this study could improve precision and efficiency in tea breeding and selection and are an important contribution towards the establishment of marker-assisted selection in tea breeding programmes.

Absorption of the novel artemisinin derivatives artemisone and artemiside: potential application of Pheroid™ technology.

Artemisinins have low aqueous solubility that results in poor and erratic absorption upon oral administration. The poor solubility and erratic absorption usually translate to low bioavailability. Artemisinin-based monotherapy and combination therapies are essential for the management and treatment of uncomplicated as well as cerebral malaria. Artemisone and artemiside are novel artemisinin derivatives that have very good antimalarial activities. Pheroid™ technology is a patented drug delivery system which has the ability to entrap, transport and deliver pharmacologically active compounds. Pharmacokinetic models were constructed for artemisone and artemiside in Pheroid™ vesicle formulations. The compounds were administered at a dose of 50.0mg/kg bodyweight to C57 BL/6 mice via an oral gavage tube and blood samples were collected by means of tail-bleeding. Drug concentrations in the samples were determined using an LC/MS/MS method. There was 4.57 times more artemisone in the blood when the drug was entrapped in Pheroid™ vesicles in comparison to the drug only formulation (p < 0.0001). The absorption of artemiside was not dramatically enhanced by the Pheroid™ delivery system.

The diagnostic yield of magnetic resonance imaging (MRI) of the brain and spine requested by general practitioners: comparison with hospital clinicians.

The rate of diagnosis of radiologically significant abnormalities in outpatients following requests of magnetic resonance imaging (MRI) of the brain and spine by general practitioners was compared with the rate following MRI scan requests by hospital clinicians. A similar rate of significant pathology was diagnosed in both groups in both the brain and the spine. Under carefully controlled conditions, open-access MRI scanning of the brain and spine can contribute to effective patient management.

Retrograde balloon dilatation for pelviureteric junction obstruction.

A total of 49 retrograde balloon dilatations for pelviureteric junction (PUJ) obstruction were carried out on 43 pelviureteric junctions in 42 patients from 1986 to 1991. The majority (34/43) were performed as primary treatment for PUJ obstruction, with 9 patients having a history of previous open pyeloplasty. Follow-up ranged from 3 months to 4 years (mean 18 months). Clinical improvement, as assessed by absence of symptoms, was seen in 34 cases (80%). There was either no change or an improvement in renographic findings (t1/2 time and/or split function) in 40 patients (93%). Of the 9 patients who were undergoing secondary treatment, 5 showed clinical improvement and 8 showed no change or renographic improvement. Nine patients required 12 further procedures, of which 5 were interval nephrectomy. Balloon pyelolysis is a simple procedure with good results over a 4-year follow-up period. It is less effective for the treatment of secondary pelviureteric junction obstruction. It has a low morbidity and no mortality, involves a short hospital stay and allows an immediate return to full activity. It is therefore an attractive alternative to open pyeloplasty as first-line treatment for PUJ obstruction.

The sensitivity of tests to detect in vivo platelet activation induced by the removal of arterial endothelium of the baboon (Papio ursinus).

The relative sensitivities for the various in vivo and in vitro tests for platelet activation are unknown. This was studied in a baboon model where limited and more substantial injury to the vascular endothelium was inflicted. The endothelium of a segment of the right carotid artery was removed with a balloon catheter on day 0 (limited de-endothelialisation), and that of the left carotid artery, abdominal aorta and left femoral artery on day 7 (substantial de-endothelialisation). Eight baboons (Papio ursinus) were used. Baseline tests for platelet activation (platelet volume, platelet density, platelet aggregate ratio, and platelet and plasma levels of platelet factor 4 [PF4] and beta-thromboglobulin [beta-TG]) were performed 7 days before de-endothelialisation and repeated on days 1, 9 and 16. The kinetics of indium-111-labelled platelets were measured after substantial de-endothelialisation. Sham operations were done on 3 animals exactly as in the test, except that the balloon injuries were not inflicted. No influence on the results of the platelet function tests was found. The only test capable of detecting limited injury to the endothelium was the measurement of plasma PF4. The mean platelet life-span (MPLS) shortened, mean platelet density decreased, the circulating platelet aggregate ratio decreased, and plasma levels of PF4 and beta-TG increased (P less than 0.05 in all instances) after the substantial endothelial injury. The mean platelet volume, intraplatelet PF4 and beta-TG, and the in vivo distribution and sites of sequestration of labelled platelets were poor tests for in vivo platelet activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Post-mortem serum concentration of cantharidin in a fatal case of cantharides poisoning.

A patient admitted to hospital died shortly after admission without a proper diagnosis having been made. Symptoms as well as the presence of a brown powder found in the possession of the deceased indicated the possibility of cantharidin intoxication. Cantharidin was positively identified by means of a GC/MS analysis, utilizing the selected ion monitoring technique (SIM), for m/z = 197.0813, (M + H+) for cantharidin, under positive chemical ionization conditions at a resolution of 7000 and a mass window of 30 ppm. Quantitation was done by means of a GC/MS SIM analysis of a toluene extract of acidified post-mortem serum under El+ conditions at a resolution of 3000, using clofibrate as internal standard and monitoring m/z = 128.0473 and 128.0029 for cantharidin and clofibrate respectively. The post-mortem serum was found to contain cantharidin at a concentration of 72.3 ng/ml whilst the cantharides powder contained 0.87% cantharidin.

Endoballoon rupture and stenting for pelviureteric junction obstruction: technique and early results.

Endoballoon rupture and stenting was performed on 31 patients with pelviureteric junction obstruction. A percutaneous antegrade approach was used in 20 patients, a retrograde technique in 11. Clinical and renographic improvement was seen in 21 patients. Four patients later underwent nephrectomy, all of whom had a GFR of less than 20% in the affected kidney. Endoballoon rupture is technically undemanding, easier and less invasive than endopyelotomy. In patients with adequate renal function it provides a suitable alternative to pyeloplasty.

Warfarin bio-availability. A comparison of 4 products.

The bio-availability of four warfarin tablet formulations--Marevan (Allen & Hanburys); Warfarin (Petersen); Coumadin (Boots) and Warfarin (Lennon)--administered as a single 10 mg oral dose, was compared in a single-blind cross-over study. Twelve healthy adult male volunteers participated in a clinical trial in which 95% confidence intervals for the true ratio (of the means) of each test product with respect to the reference product (Marevan) were calculated for maximum concentration and area under the plasma concentration time curve. The three test products differed by less than 20% from the reference product, suggesting that all four can be used interchangeably without risk of compromising safety and efficacy.

Gas chromatographic-mass spectrometric method for the quantitation of cantharidin in human serum.

A gas chromatographic-mass spectrometric (GC-MS) method utilising single-ion monitoring at a resolution of 3000 to quantitate cantharidin in post-mortem serum is described. Serum was acidified, extracted with toluene, and 1 microliter of the toluene extract subjected to GC-MS analysis. Clofibrate was used as internal standard. The method displayed a high degree of specificity and was accurate and precise, with a linear response in the concentration range 15-150 ng/ml. A cantharidin concentration of 72.3 ng/ml was found in the post-mortem serum.

A comparison of T1 measurements at 1.7 and 3.4 MHz in the diagnosis of prostatic carcinoma.

To compare the specificity of T1 measurement for the diagnosis of prostatic carcinoma in vivo, two groups of patients with clinically enlarged prostate glands have been imaged. One group comprising 25 patients was imaged at 1.7 MHz the other comprising 51 patients at 3.4 MHz. T1 measurements together with the gross anatomical appearances of the prostate gland were observed and compared with the clinical and histologic diagnoses. At 1.7 MHz it was found that the T1 measurement of carcinoma of the prostate and benign hypertrophy of the prostate fell into two distinct ranges with no overlap between the two conditions. Three false-positive diagnoses of carcinoma were made in patients with prostatitis where the T1 values fell in the upper part of the carcinoma range. T1 measurement in the group studied at 3.4 MHz demonstrated no specific value for either condition and diagnosis of malignancy had to be made from the morphologic appearances of the gland. Morphologically benign hypertrophy appeared homogeneous while carcinoma appeared heterogeneous with small areas of increased T1 in the malignant part of the gland.