Chitosan microspheres as a potential carrier for drugs.

Chitosan is a biodegradable natural polymer with great potential for pharmaceutical applications due to its biocompatibility, high charge density, non-toxicity and mucoadhesion. It has been shown that it not only improves the dissolution of poorly soluble drugs but also exerts a significant effect on fat metabolism in the body. Gel formation can be obtained by interactions of chitosans with low molecular counterions such as polyphosphates, sulphates and crosslinking with glutaraldehyde. This gelling property of chitosan allows a wide range of applications such as coating of pharmaceuticals and food products, gel entrapment of biochemicals, plant embryo, whole cells, microorganism and algae. This review is an insight into the exploitation of the various properties of chitosan to microencapsulate drugs. Various techniques used for preparing chitosan microspheres and evaluation of these microspheres have also been reviewed. This review also includes the factors that affect the entrapment efficiency and release kinetics of drugs from chitosan microspheres.

Cyclosporine trough levels in renal graft recipients.

Blood Trough Levels (TL) of cyclosporine (CyA) [the drug panimun bioral cyclosporine oral solution USP--modified. Panacea Biotec Ltd], were monitored in 103 renal transplant patients who were receiving CyA orally. Two hundred and sixty-two blood concentrations of CyA were determined using a validated HPLC assay over a period of two years. Mean dose from week 1 until 2 years ranged from 7.65 +/- 0.9 to 2.73 +/- 0.8 mg/kg. Mean blood CyA levels ranged from 197.4 +/- 87.5 to 205.9 +/- 113.5. The TL concentration changes versus dose reduction were not markedly different after 2-4 weeks and remained within therapeutic range. Stabilised concentrations were achieved after first month. We conclude that the blood TL of CyA were in the nominal therapeutic range suitable for renal transplant patients.

Dietary vitamin B6 supplementation prevents ethanol-induced hypertension in rats.

BACKGROUND AND AIMS: All known pathways of ethanol metabolism result in the production of acetaldehyde, a highly reactive compound. Acetaldehyde has been shown to deplete vitamin B6 in chronic alcoholics. It also binds with sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing vascular cytosolic free calcium, peripheral vascular resistance and blood pressure. The aldehyde-binding thiol compound, N-acetyl cysteine, attenuates elevated blood pressure and associated adverse changes in ethanol-induced hypertensive rats. Vitamin B6 supplementation increases the level of endogenous cysteine. Aim of this work was thus to investigate whether a dietary supplementation of vitamin B6 can prevent ethanol-induced hypertension and associated changes in Wistar-Kyoto (WKY) rats. METHODS AND RESULTS: Starting at 7 weeks of age, WKY rats were divided into three groups of six animals each. The control group received a normal vitamin B6 diet (regular chow) and normal drinking water, the ethanol group, the same diet plus 1% ethanol in the drinking water, and the ethanol + vitamin B6 group a high vitamin B6 diet (20 times normal diet) and 1% ethanol in the drinking water. After 14 weeks, systolic blood pressure, platelet [Ca2+]i and kidney and aortic aldehyde conjugate levels were significantly higher in the ethanol group. These rats also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin B6 supplementation prevented these changes. CONCLUSIONS: Dietary vitamin B6 supplementation prevented ethanol-induced hypertension and associated changes in WKY rats by normalizing tissue aldehyde conjugate levels.

Role of aldehydes in fructose induced hypertension.

Aldehydes are formed in tissues of humans and animals as intermediates of glucose and fructose metabolism and due to lipid peroxidation. N-acetyl cysteine (NAC), an analogue of the dietary amino acid cysteine, binds aldehydes thus preventing their damaging effect on physiological proteins. We measured systolic blood pressure (SBP), platelet cytosolic free calcium [Ca2+]i and tissue aldehyde conjugates in fructose induced hypertensive Wistar-Kyoto (WKY) rats and examined the effect of NAC in the diet on these parameters. Animals age 7 weeks were divided into three groups of 6 animals each and were treated as follows: WKY-control (chow diet and normal drinking water); WKY-Fructose (chow diet and 4% fructose in drinking water); WKY-Fructose+NAC (1.5% NAC in chow diet and 4% fructose in drinking water). After 11 weeks, systolic blood pressure, platelet [Ca2+]i and kidney aldehyde conjugates were all significantly higher in fructose treated rats. NAC treatment prevented these changes. These results suggest that aldehydes may be the cause of fructose induced hypertension and elevated cytosolic free calcium.

Aldehyde induced hypertension in rats: prevention by N-acetyl cysteine.

Methylglyoxal, a highly reactive endogenous aldehyde is formed in the tissue of humans and animals as an intermediate of glucose and fructose metabolism. N-acetyl cysteine (NAC), an analogue of the dietary amino acid cysteine, binds aldehydes thus preventing their damaging effect on physiological proteins. We measured systolic blood pressure (SBP), platelet [Ca2+]i, circulating nitric oxide levels, tissue aldehyde conjugates and renal vascular changes in chronic methyglyoxal treated Wistar-Kyoto (WKY) rats and examined the effect of NAC in the diet on these parameters. Animals, age seven weeks, were divided into three groups of six animals each and were treated as follows: WKY-control (chow diet and normal drinking water); WKY-methylglyoxal (chow diet and methyglyoxal in drinking water); WKY-methyglyoxal + NAC (1.5% NAC in diet and methylglyoxal in drinking water) for the next 18 weeks. Methylgyoxal in drinking water was given at a concentration of 0.2% during weeks 0-5; 0.4%, weeks 6-10; and 0.8%, weeks 11-18. After 18 weeks systolic blood pressure, platelet [Ca2+]i and kidney aldehyde conjugates were significantly higher and serum nitric oxide levels lower in methylglyoxal treated rats. Methylglyoxal treated rats also showed smooth muscle cell hyperplasia in the small artery and arterioles of the kidney. N-acetyl cysteine, an aldehyde binding thiol compound, prevented these changes.

A review of urinary fistulae in a university teaching hospital.

An 8-year study of urinary fistulae from 1974 to 1981 was done in the University Teaching Hospital, Lusaka, Zambia. The analysis revealed no significant decrease in the number of urinary fistulae referred to the Department of Obstetrics and Gynaecology of the University during the period. Of 61 cases reviewed, 54 were consequent to obstetrical trauma of prolonged labor and superimposed operation or instrumentation. Four fistulae occurred as a complication of gynecologic surgery, while three originated from advanced malignancy of the cervix. Operative management of fistulae is discussed. Further reorganization of rural maternity services in Zambia is suggested as a preventive measure.

PIP: A retrospective study of 163 cases of urinary fistulae in the Department of Obstetrics and Gynecology of the University Teaching Hospital, Lusaka, Zambia, from 1974-1981 were analyzed. 82 were operated; 61 cases had sufficiently complete records for this study, and 44 operations are reported. 25.9% were teenagers, 26.2% were ages 20-30; 37.6% were primigravidas. 88.5% were obstetric fistula, the rest were associated with hysterectomy or cervical cancer. 59.2% were juxtaurethral, most common in obstructed labor. Mid-vaginal fistulae, easier to repair, were next common (20.8%). A rare case of vesico-uterine fistula after cesarean section, associated with cyclic hematuria but no urine leakage, was noted. 82 were operated, with an overall cure rate of 59.1%. Types of surgeries were transvaginal flapsplitting in 29 with 68.9% success, Martius procedure in 3 with 66.7% success, and transvesical approach in 9 with 44.4% success. There was also 1 suprapubic urethral reconstruction, 1 flapsplitting with reconstruction of the urethra, and 1 urinary diversion.

Outcome of labor following previous cesarean section.

Four hundred fifty-one patients who had had previous lower segment cesarean section were studied for subsequent pregnancy outcome at the University Teaching Hospital, Lusaka, Zambia. Of 319 who were allowed to go into labor, 63% succeeded in delivering vaginally, while 37% had to undergo repeat intrapartum cesarean delivery. No maternal death occurred. Scar dehiscence occurred in one case only. Parturition in otherwise obstetrically normal patients seems to be safe, and the trial of labor approach is desirable as it results in a lower number of repeat cesarean deliveries.

Obstetric problems in the adolescent Zambian mother studied at the University Teaching Hospital, Lusaka.

The Obstetric performance of teenage primigravida aged 12-15 years was studied retrospectively and analysed in the local population attending the University Teaching Hospital, Lusaka. The leading Obstetric complications were cephalo-pelvic disproportion (3.6%) and acute toxeamia (2.2%). The caesarean section rate (7.5%) and operative vaginal delivery rate (11%) were both high. There was one maternal death due to Obstetric shock. The rates for prematurity (154/1,000), still births (30.8/1000), and neonatal death (101.9/1,000) were increased. Perinatal mortality rate was 123/1,000. The incidence of pregnancy between 12-15 years was 1.2%. Overall incidence of teenage pregnancy (12-19 years) was 22.5% and parity of 5 was observed at the age of 18 and 19. The study concluded that early teenage pregnancy carried obstetrical risks and was associated with a high perinatal loss.

Role of cervical cytology in gynaecological practice.

Exfoliative cytopathology is a potent tool for the early detection and thereby eradication of cervical cancer and reducing mortality for many others. Besides, it has a vital role to play in diagnosis and therapy of infections specially trichomoniasis for which it gives a permanent record. The simplicity and rapidity of the technique is the greatest advantage for screening a wider group of population and thus guide us toward further diagnostic procedures.

Obstetrical performance in elderly Zambian parturients.

The Obstetrical performance of elderly parturients (aged 40 and above) who delivered at the University Teaching Hospital, Lusaka during 1979 and 1980, has been analysed. There were 39,109 deliveries in the two years period, out of which 391 mothers were of 40 years or above, giving an incidence of 1.0%. There were 32 mothers above the age of 45, an incidence of 0.08%. Analysis of these mothers revealed that 87.2% of them were grand multipara with maximum parity of 16. Incidence of breech, toxaemia, malpresentation and multiple pregnancy were observed in the series but there was no maternal death recorded in the present study. History of abortion in previous pregnancies ranging from 1 to 5 was noted in 43 cases. Operative deliveries were noted in 22% cases, out of which 13% were delivered by caesarean section and 9% had to undergo operative vaginal interference. In the foetal outcome, high rates of prematurity (71/1,000) and perinatal death (138/1,000) were noted. Relations of birth weights, age and parity of mothers with preventable factors are discussed.