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Biomedical subjects

F M Ali

Publications and source records attributed to F M Ali.

At least 19 recordsLinked to original sources

Prolonged effect of liposomes encapsulating pilocarpine HCl in normal and glaucomatous rabbits.

The possibility of using liposomes as an ophthalmic drug delivery carrier for the lipophilic drug, pilocarpine HCl, was investigated on the eyes of normal and glaucomatous pigmented rabbits. The intraocular pressure (IOP) of rabbits was measured, using a Shi∅tz tonometer, as a function of time after topical administration with free drug, neutral and negatively charged multilamellar vesicles (MLVs) encapsulating pilocarpine HCl. The results showed that administration with neutral MLVs displayed the most prolonged effect with respect to negatively charged MLVs and free drug. The efficiency of MLVs encapsulating pilocarpine HCl, measured using spectrophotometric technique, was found to be 96% in our modified preparations. The storage stability of MLVs encapsulating pilocarpine HCl was investigated by measuring phase transition and size distribution using light scattering technique. The results show that liposomes encapsulating pilocarpine HCl have kept their integrity and physicochemical properties for at least 15 months, which makes them suitable for commercial use.

1,2-Dipalmitoylphosphatidylcholine↗

Membrane solubilization in erythrocytes as a measure of radiation exposure to fast neutrons.

Membrane solubilization and osmotic fragility of rat erythrocytes irradiated in vivo with fast neutron fluences ranging from 10(6) to 5 x 10(7) n cm(-2) using a 252Cf source were measured instantaneously using a light scattering technique. The solubilization of erythrocyte membrane by a non-ionic detergent, octylglucoside (OG), was found to exhibit a two stage transition from vesicular form to mixed micellar form in the range of detergent concentrations 1.5-7.8 mM. The coexistence phase, vesicular/mixed micellar, was shifted towards higher detergent concentrations with increase in the neutron fluence, indicating increasing membrane resistance to the detergent and hence change in the natural membrane permeation properties. The technique shows an adequate sensitivity in detecting membrane damage in erythrocytes and has potential as a biophysical marker of radiation exposure. The osmotic fragility of irradiated erythrocytes shows a decreasing trend with increasing irradiation fluence measured directly and two weeks post-irradiation. Blood films photographed two weeks post-irradiation show developed elliptocytosis and crenated cell anaemia.

Animals↗

Serum-hydroxyapatite interaction in vitro.

In a project to develop hydroxyapatites for bone replacement, biological and synthetic types were prepared at 600 degrees C, ground to 300-600 microns and immersed in a pooled human serum for periods up to 1 month at 4 degrees C to assess material interaction. It was found that the levels of calcium in the serum were reduced at 6 h immersion, followed by an increase to reach maximum at 48 h and then stability up to 1 month. Phosphorus levels showed the opposite behaviour. Both apatites showed similar trends, although higher values were recorded for the synthetic type, suggesting higher activity. Infrared spectral analysis complemented the biochemical values, where the optical densities (O.D.) of phosphate groups were reduced, reflecting the increased phosphorus in serum and denoting leaching. Also, O.D. values of both CO3(2-) and OH- groups were reduced at 10 h, then returned to original levels. Scanning electron microscopy revealed a spongy appearance parallel with reduced O.D. and higher levels of serum Ca2+. At longer periods (48 h) the concentric needles of hydroxyapatite are clearly shown to be deposited on biological apatite. Differences in responses were attributed to their original crystalline structure assessed by X-ray diffraction analysis, as well as pore analysis using a mercury porosimeter.

Bone Resorption↗

Incidence of nasal carriers of Staphylococcus aureus in and outside hospital environment and antibiotic sensitivity of isolated staphylococcus strains.

This study was carried out on 100 nasal swabs collected from medical personnel (nurses and doctors) and patients inside hospital environment and also from 50 individuals outside hospital. The swabs were inoculated on different culture media for isolation of /staphylococci which were further identified as S. aureus either by classic bacteriologic methods or by one of rapid screening test of S. aureus. The isolated strains were tested for antibiotic sensitivity to some of B-Lactam antibiotics and to other antibiotics. The results showed that significantly higher percentage of coagulase + ve Staph. were isolated from newborn nursery (90%), operating theatre (71.4%) and hemodialysis unit (60%) than those isolated from intensive care unit, cancer chemotherapy, surgery, chest, internal medicine departments (25%, 26.6%, 31.2%, 33.3%, 50%) respectively. It also showed significant difference in isolation rate between persons at the hospital (patients, doctors and nurses) 44% and controls (normal population) 26%. Most isolates of coagulase + ve Staph. were resistant to penicillin G (93.2%), Streptomycin (77.3%), tetracycline (61.4%) and sensitive to cefamandole (95.4%). All coagulase+ve Staph. isolates were resistant to sulphonamide and methicillin and all sensitive to vancomycin.

Carrier State↗

Rapid increase of both HIV-1 infection and syphilis among pregnant women in Nairobi, Kenya.

OBJECTIVE: To determine the prevalence of HIV-1 and syphilis antibodies in a population of pregnant women in Nairobi, Kenya, between 1989 and 1991. METHODS: As part of an ongoing prospective study on the effect of HIV-1 infection and sexually transmitted diseases, 4883 pregnant women were screened for HIV-1 and syphilis antibodies in one health-centre in Nairobi. RESULTS: HIV-1 seroprevalence increased from 6.5 to 13.0% (P < 0.001) and syphilis seroreactivity from 2.9 to 5.3% (P = 0.002), while there was no change in gonococcal infection rates. The most rapid increase in HIV-1 prevalence was observed in women aged less than 25 years. There was no evidence of demographic fluctuations in the population during this time, or of changes in sexual behaviour, except that fewer women enrolled in 1991 reported having more than one sex partner, compared with women enrolled in 1989 (39.1 versus 20.0%; P = 0.0001). HIV-1-seropositive women were more likely to be seroreactive for syphilis than HIV-1-seronegative mothers (7.7 versus 3.2%; odds ratio = 2.5; 95% confidence interval, 1.7-3.8; P < 0.001), but there was no difference between the two groups in terms of gonorrhoea prevalence. CONCLUSION: These data confirm an association between HIV-1 and syphilis infection, and indicate that both are spreading rapidly among women in Nairobi outside high-risk groups. Increased efforts to control both infections are urgently required.

Antibodies, Viral↗

Platelet-monoamine oxidase activity in Reye's syndrome.

Platelet and liver monoamine oxidase (MAO) activity (mean +/- SD) was evaluated in patients with liver-biopsy-proven Reye's syndrome. MAO was measured by a radioenzymatic technique with [3H]tyramine as a substrate. A marked decrease in MAO activity [3.3 +/- 2.4 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] was observed in platelets on admission in all patients (n = 13) with Reye's syndrome when compared with hospitalized patients without liver disease (n = 8) [9.8 +/- 2.5 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] and with liver disease (n = 10) [9.1 +/- 2.0 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1]. Following recovery from the disease, platelet MAO approached levels that were not significantly different from those of controls. Contrastingly, reduction of hepatic MAO in Reye's syndrome was similar to that seen in patients with liver disease of different etiologies. These studies suggest that reduced platelet MAO activity is a specific abnormality in Reye's syndrome, and it may be representative of generalized impairment of mitochondrial function in these patients. Furthermore, the pattern of liver and platelet MAO activity in Reye's syndrome may allow for the differentiation of this disease from other hepatopathologic conditions.

Adolescent↗

Separation of malignant plasma cells from the bone marrow of patients with myelomatosis.

Complement-mediated lysis of bone marrow cells from patients with myelomatosis using a rabbit antiserum raised against normal peripheral blood mononuclear cells was found to greatly enrich the abnormal plasma cells. Cellular morphology was good and the cells were able to synthesize and secrete paraprotein. This was found to be a quick and useful method of preparing myeloma plasma cells for further studies of their metabolic properties.

Bone Marrow↗

Preparation and biodistribution of 99mTc-labeled tyramine iminodiacetic acid.

The synthesis and biodistribution properties of 99mTc-labeled N-substituted tyramine, [N-(4-hydroxyphenethyl)iminodiacetic acid] are described. Tissue distribution studies in rats were indicative of high hepatic and kidney extraction, accompanied by rapid plasma and urinary clearance and minimal biliary excretion. These findings were substantiated by organ image analysis. The preliminary data indicate that this labeled material may represent a new class of radiopharmaceuticals for the evaluation of hepatic and renal functions.

Animals↗

Evaluation of transsphenoidal hypophysectomy in the management of patients with advanced malignant melanoma.

Transsphenoidal hypophysectomy was performed in 13 patients with advanced malignant melanoma. Although three minor responses were observed, there were no complete or partial responses. All three patients with bone pain had a decrease in discomfort lasting 1-2 months. All five patients with minor responses or stable disease had postoperative decreases in the excretion of the dihydroxyphenylalanine (DOPA) metabolite 3-O-methyldopamine; all but one patient with clinical progression had postoperative increases in excretion. Average survival of those whose postoperative excretion fell (143 +/- days; range, 60-217+) was significantly longer (P less than 0.004) than that of those whose postsurgical values rose (30 days; range, 15-58).

Adult↗

Enrichment of erythroblasts from human bone marrow using complement-mediated lysis: measurement of ferritin.

Sequential lysis of human bone marrow cells with a monoclonal antibody directed against myeloid cells (TG1) and a rabbit antiserum raised against peripheral blood mononuclear cells gave preparations in which 78-97% of the nucleated cells were erythroid, with a 24-77% recovery. Viability was high, morphology was good and the cells were able to divide and differentiate in culture. No metabolic experiments were carried out but the ferritin content of the erythroblasts was measured in four experiments and found to be about 200-2000 times higher than that found in normal erythrocytes. The H/S ratio was high in both erythroblasts and erythrocytes. Fractionation on the basis of density of two erythroblast preparations, one from a patient with sideroblastic anaemia and one from a patient with megaloblastic anaemia, showed that the most immature erythroblasts contained the highest content of ferritin and that this fell with maturation. The H/S ratio stayed the same or fell with maturation. It was concluded that this method would be valuable for the study of the role of erythroblast ferritin in normal and pathological situations.

Anemia, Megaloblastic↗

Similarity between tyramine-induced neurotoxicity and the coma of Reye's syndrome.

The objective of the present investigation was to determine whether or not tyramine induces coma in experimental animals with impaired mitochondrial monoamine oxidase function, and whether the coma in these animals was a function of increased cerebrospinal fluid (CSF) pressure. Ten mongrel dogs were treated (orally) daily with the monoamine oxidase-inhibiting drug, phenelzine (4.5 mg/kg), over a period of 1 month. The present studies indicated that in phenelzine-treated animals with liver disease and behavioral side effects (n = 4), the i.v. administration of tyramine (1 mg/kg) caused substantial elevation in CSF pressure that exceeded 30 mm Hg (initial pressure 12.5 +/- 2.1). This was followed by substantial accumulation of tyramine, dopamine and norepinephrine concentrations in CSF of these animals. The animals became comatose soon afterward. The administration of tyramine to pretreated (n = 10) or phenelzine-treated animals without liver disease (n = 6) caused only the expected transient increase in blood pressure but with no significant effect on CSF pressure of these animals. These animals recovered fully from the experiment without any ill effect. These studies suggest that tyramine may have obvious implications in the development of intracranial hypertension in Reye's syndrome.

Animals↗

A two-step procedure for obtaining normal peripheral blood T-lymphocytes using continuous equilibrium density gradient centrifugation on percoll.

Equilibrium centrifugation of either peripheral blood mononuclear cells or of pure lymphocytes (obtained by carbonyl iron or glass bead adherence removal of monocytes) on a continuous density gradient of Percoll yielded lymphocyte fractions containing between 92 and 99% T lymphocytes as shown by sheep red blood cell rosetting. B lymphocytes with surface immunoglobulin were found in the regions of low density (1.03-1.065 g/ml) and T lymphocytes in the regions of higher density (1.06-1.08 g/ml). TM lymphocytes with their characteristic positive 'dot' pattern of staining for non-specific esterase were also found mainly in regions of high density. It was concluded that Percoll continuous equilibrium density gradient centrifugation can be used to obtain T lymphocytes in high yield, with high viability and without metabolic changes which may occur after contact with sheep red blood cells. The esterase staining suggested that there was also some separation of T lymphocyte subsets.

Cell Separation↗

Hepatorenal failure induced by tetracycline in dogs with portacaval shunt.

The aim of the present investigation was to determine whether tetracycline accelerated the hepatic toxicity of portacaval anastomosis and whether this could be reflected by changes in pharmacokinetics of the drug. Side-to-side portacaval shunts were constructed and converted to end-to-side by ligating the hepatic side of the portal vein in dogs. The results of this study showed that the i.v. infusion of tetracycline (50 mg/kg) to shunted animals caused rapid deterioration in hepatic and renal functions followed by the eventual transition of these animals from stage I to stage II liver disease. This was reflected by a 3- to 6-fold increase in the serum level of bilirubin, alkaline phosphatase, serum glutamic-oxalacetic transaminase, blood urea nitrogen and creatinine as compared with the levels of those produced in serum of dogs before and after the construction of the shunt before the administration of tetracycline. Kinetic analysis revealed a significant prolongation in the elimination half-life (38.2 +/- 4.2 hr) of the shunted dogs as compared with controls (14.5 +/- 1.5 hr) after the i.v. administration of tetracycline. This was accompanied by an appreciable reduction of elimination rate constant. In contrast to shunted animals, control animals exhibited no behavioral side effects after the administration of tetracycline.

Animals↗

Tyrosine transaminase activity in normal and cirrhotic liver.

Most cirrhotics have tyrosinemia and subnormal tyrosine tolerance; in some the ability to metabolize p-hydroxyphenylpyruvic and homogentisic acids is impaired. In previous studies, the initial transamination appeared to be the rate-limiting step. In this study, hepatic tyrosine transaminase activity was compared in liver biopsies from eight noncirrhotic and ten cirrhotic subjects to determine whether the subnormal tyrosine tolerance was related to decreased maximal activity of this enzyme. Fasting plasma tyrosine in the cirrhotics (133 +/- 43 micromol/liter) was significantly higher (P less than 0.005) than in the noncirrhotic subjects (64 +/- 25 micromol/liter). Tyrosine transaminase activity in the cirrhotic livers (42 +/- 11 micromol PHPA/g liver/hr, or 0.47 +/- 0.1 micromol PHPA/mg protein/hr) was not significantly different from the enzyme activity in the noncirrhotic liver (43 +/- 7 micromol PHPA/g liver/hr, or 0.39 +/- .12 micromol PHPA/mg protein/hr.) Thus elevated tyrosine levels in cirrhotics cannot be explained by decreased tyrosine transaminase activity in the liver, and other explanations must be sought.

Aged↗

Evidence for central hypertyraminemia in hepatic encephalopathy.

In mongrel dogs, the effect of end-to-side portacaval shunt on plasma, cerebrospinal fluid (CSF) and brain tyramine, tyrosine, dopamine, norepinephrine, and epinephrine were studied. It was found that the level of tyramine in plasma, CSF, and selected brain regions increased steadily after the construction of the shunts. These elevations became more pronounced when the dogs manifested symptoms of hepatic encephalopathy. In postshunted dogs with stage II and III hepatic encephalopathy, tyramine concentration in corpus striatum (1,312 +/- 371), hypothalamus (400 +/- 67.0), and midbrain (660 +/- 78.7 ng/g) was significantly (P less than 0.05) higher than the level in dogs with stage 0 and I hepatic encephalopathy and sham-operated dogs serving as controls (corpus striatum, 831 +/- 140; hypothalamus, 167 +/- 40.0; and midbrain, 132 +/- 37.4 ng/g). This was followed by a concomitant depletion of dopamine and norepinephrine in these brain regions (postshunt: dopamine 104 +/- 20.0, 3,697 +/- 977, and 105 +/- 14.1; norepinephrine 521 +/- 71.6, 81.6 +/- 13.7, and 218 +/- 31.7 ng/g; vs. sham group: dopamine 532 +/- 83.1, 8,210 +/- 1,126, and 192 +/- 35.0; norepinephrine 1,338 +/- 425, 124 +/- 21.3, and 449 +/- 89.7 ng/g) of encephalopathic dogs with portacaval shunt. Furthermore, tyramine, tyrosine, dopamine, and norepinephrine levels in plasma and CSF increased markedly as clinical features in the dogs' behavior characteristic of hepatic encephalopathy occurred, including hypersalivation, ataxia, flapping tremor, somnolence, and coma. Cerebral hypertyraminemia and a defect in sympathetic neurotransmission may contribute to the development of hepatic encephalopathy of liver disease.

Animals↗

Melanoma detection by enzyme-radioimmunoassay of L-dopa, dopamine, and 3-O-methyldopamine in urine.

This enzyme-radioimmunoassay for the measurement of L-dopa, dopamine, and 3-O-methyldopamine is based on the incubation of urine in the presence of catechol-O-methyltransferase, aromatic-L-amino-acid decarboxylase, and S-adenosylmethionine. The O-methylated dopamine metabolite formed, 3-O-methyldopamine, was characterized by radioimmunoassay. To evaluate the role of L-dopa metabolism in melanoma, we used the enzyme-radioimmunoassay to assess concentrations of L-dopa, dopamine, and 3-O-methyldopamine in urine from 10 healthy subjects, 10 hospitalized patients without melanoma and 28 patients with different degrees of melanoma. The effect of surgery for melanoma on urinary output of these catechols of melanoma patients was also evaluated. No significant difference in urinary L-dopa, dopamine, and 3-O-methyldopamine excretion rates was seen between normal subjects (L-dopa 1.3 +/- 0.3, dopamine 147 +/- 38, and 3-O-methyldopamine 31.4 +/- 13.6 microgram/24 h), hospitalized patients without melanoma, and amelanotic melanoma patients. However, the excretion rates for these metabolites in melanotic melanoma (L-dopa 5.6 +/- 1.2, dopamine 555 +/- 121, and 3-O-methyldopamine 178 +/- 40.3 microgram/24 h) were significantly (p < 0.005) higher than in control or amelanotic melanoma subjects. After surgery, there was a substantial decrease in urinary output of L-dopa and its metabolites by these patients.

Adolescent↗