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PubMed2005

Pharmaceutical applications of mucoadhesion for the non-oral routes.

The adhesion of pharmaceutical formulations to the mucosal tissue offers the possibility of creating an intimate and prolonged contact at the site of administration. This prolonged residence time can result in enhanced absorption and, in combination with a controlled release of the drug, also improved patient compliance by reducing the frequency of administration. During the almost 30 years over which mucoadhesion has been studied, a considerable amount of knowledge has been gained, and much has been learned about the different mechanisms occurring at the formulation-mucus interface and the properties that affect these mechanisms. The in-vivo performance of a dosage form not only depends on the mechanisms occurring at the interface, but also on the properties of the total mucoadhesive complex: the dosage form, the mucosa and the interface between them. A wide variety of methods are used for studying mucoadhesion; some rather similar to the in-vivo situation and some mimicking the interface alone. In this review, the mucus surface, the methods used for the study of mucoadhesion, the different mechanisms involved in mucoadhesion and theories underpinning them have been described. The complexity of mucoadhesion when trying to systemize the subject will also be discussed. The last part of the review describes the buccal, nasal, ocular, vaginal and rectal routes and provides examples of what can be achieved in-vivo when using mucoadhesive formulations.

Animals↗

PubMed1995

Naloxone exacerbates intestinal and systemic anaphylaxis in the rat.

Following sensitization to ovalbumin (OA), male Wistar rats were pretreated with naloxone (20 mg/kg i.p.) and subjected to antigen challenge (3 mg OA i.p.). Naloxone exacerbated both systemic and intestinal anaphylaxis when injected 10 and 90 min before the antigen challenge. This was evidenced by a more pronounced drop in rectal temperature, higher hematocrit values, and by an enhanced elevation of basal short-circuit current (an indication of the secretory tone of the small intestine studied in Ussing chambers). Pretreatment with an equipotent does of methylnaloxone (200 mg/kg i.p.), a peripherally acting opiate antagonist, exacerbated the indices of intestinal anaphylaxis but had no apparent effect on indices of systemic anaphylaxis. Thus, our data strongly suggest that in the rat, components of the systemic hypersensitivity reaction are mediated through central opioid receptors, whereas the changes in gut function characterizing intestinal anaphylaxis are mediated through peripheral opioid receptors.

Anaphylaxis↗

PubMed1998

The use of stable isotope techniques for nutritional and metabolic research in paediatrics.

Stable isotope methods are increasingly used in paediatrics for clinical diagnosis and research due to marked improvements in analytical technologies and better availability of suitable tracers. The safety of stable isotopes is of major importance for use in children. Large amounts of deuterium well above the doses applied under clinical conditions may induce adverse effects. In contrast, heavier stable isotopes such as 13C, 15N or 18O do not induce adverse effects even at the highest enrichments obtained, and they are safe. Breath tests with measurements of 13CO2 enrichment after oral application of a tracer can reliably evaluate helicobacter pylori infection and gastric emptying kinetics. Combined with an estimation of total CO2 production, 13CO2 breath tests allow estimation of the absorption and oxidation of 13C-labelled substrates, such as medium- and long-chain triglycerides, and demonstrates the beneficial effect of carnitine supplements on fat oxidation in primary carnitine deficiency. The study of metabolic processes may require the sampling of blood for isotopic analyses of metabolites of the applied tracer. Gas chromatography-isotope ratio mass spectrometry can detect tracer in individual components from small plasma samples. The high precision enabled us to utilize the small differences in natural 13C-enrichment between dietary fats to study fatty acid turnover in term infants, in whom the dietary fat source was switched to corn oil with a slightly higher 13C-content. With this approach we demonstrated active conversion of linoleic into arachidonic acid. We also applied biotechnologically produced, U-13C labelled linoleic and alpha-linolenic acids to infants and detected the conversion of these essential fatty acids to their longer chain polyunsaturated derivatives, with an apparent change of conversion activity with age. Moreover, it has become possible to measure tissue protein synthesis from small biopsy samples obtained in situ without surgery, such as forceps biopsies of rectal tumors. These few examples of recent developments demonstrate the great clinical and scientific potential of stable isotope methods in future paediatric applications.

Carbon Isotopes↗

PubMed1984

[Pharmacokinetics and the effects of metronidazole during its use as a radiosensitizer].

During gamma-beam therapy (40-60 Gy) a study was made of the content of metronidazole (MZ) in the blood of 20 patients with oral mucosa cancer and 12 patients with esophageal cancer depending on a mode of its administration. A MZ effect on liver and renal function was studied. MZ was administered to the patients with cancer of both sites on the first 3 days of radiation therapy 3 h before an enlarged fraction of 4 Gy, estimated at 145 mg per 1 kg body mass (8-10 g) per os or via a gastrostoma and 15 g in rectal administration. In the patients with oral mucosa cancer after the administration of MZ per os its level which was sufficient for radiosensitization, was achieved after 2 h and remained for subsequent 4 h with maximum accumulation of 262 +/- 22 micrograms/ml in the blood serum 3-4 h after administration. In 24 h there remained 84 +/- 9 micrograms/ml of MZ in the blood (32% of its maximum level). In the patients with esophageal cancer after MZ administration via the gastrostoma, the nature and time course of drug accumulation in the blood was identical, however accumulation maximum was lower and reached 219 +/- 25 micrograms/ml. In the patients with esophageal cancer after MZ rectal administration, its level in the blood was 118 micrograms/ml only and did not achieve a therapeutically effective level. In repeated administration of MZ per os or via the gastrostoma its accumulation by 25-30% was observed. MZ caused a transient increase in the permeability of the cell membranes of the liver and the suppression of its protein-forming function. It is assumed that the lowering of MZ repeated dose by 20% will cause a decrease in the drug accumulation in the body and the degree of a toxic effect with maintaining its therapeutically effective level in the blood and tumor.

Adult↗

PubMed1984

Nifedipine kinetics and dynamics during rectal infusion to steady state with an osmotic system.

Nifedipine steady-state kinetics and dynamics were investigated in a placebo-controlled study of six healthy subjects. Nifedipine was given rectally through an osmotic system at a zero-order rate for 24 hr. Steady-state plasma concentrations of approximately 20 ng/ml were achieved within 6 to 8 hr. Nifedipine lowered diastolic blood pressure (DBP) and increased forearm blood flow (FBF) and plasma norepinephrine concentration. On the other hand, heart rate (HR) and systolic blood pressure were not affected. Changes in DBP and FBF were closely related to nifedipine plasma concentrations during and immediately after the infusion period. Our data indicate that nifedipine lowers blood pressure in subjects with normotension and that it is possible by infusing the drug at a relatively low rate to dissociate its effect on blood pressure from that on HR.

Absorption↗

PubMed1992

[A case of early syphilis presenting general paresis-like symptoms and bilateral tonic pupils].

A 40-year-old man was admitted after 8 months of speech disturbance and locomotive ataxia. He had no seizures, lightning pains, paresthesia, visual loss, bladder disturbance or rectal incontinence. He had never been neurologically or psychiatrically ill and had no history of syphilis. When the patient was admitted, his general physical examination including blood pressure and dermatologic examination was normal. His consciousness was alert. He was found to have a deterioration of mental status such as inability to concentrate, failing memory, amnesia and circumstantiality. His pupils were anisocoric and Achilles jerks were absent. No rigidity of the neck muscles, paralysis and sensory disturbance were recognized. Romberg's sign was absent. The right pupil was 7.0 mm and the left was 6.0 mm in room illumination. The pupils were nonreactive to bright light and both did not constricted to near stimuli. 0.125% pilocarpine eyedrops produced bilateral pupillary constriction. The results indicated bilateral tonic pupils. Laboratory data revealed white cell count of 12,600/mm3 and normal erythrocyte sedimentation rate of 8 mm/hr. Cerebrospinal fluid (CSF) examination revealed the following: opening pressure, 140 mm of water; cell counts, 76/mm2 (mononuclear cells); total protein, 116 mg/dl; glucose, 57 mg/dl. A serum venereal disease research laboratories (VDRL) test was positive in a 1:32 titer confirmed by positive treponema pallidum hemagglutination (TPHA) test in a 1:40,960 titer and positive fluorescent treponemal antibody-absorption (FTA-ABS) test. Serum TPHA-IgM was positive in a 1:320 titer but TPHA-IgG was negative. CSF examination revealed positive TPHA test (titer of 1:2,560) and positive FTA-ABS test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men.

Mortality rates from colon cancer in the USA are highest in populations exposed to the least amounts of natural sunlight; differences in endogenous vitamin D production and calcium absorption could be responsible. To investigate this possibility, the association of dietary vitamin D and calcium with 19-year risk of colorectal cancer was examined in 1954 men who had completed detailed, 28-day dietary histories in the period 1957-59. Risk of colorectal cancer was inversely correlated with dietary vitamin D and calcium. In the quartiles of a combined index of dietary vitamin D and calcium, from lowest to highest, observed risks of colorectal cancer were 38.9, 24.5, 22.5, and 14.3/1000 population. This association remained significant after adjustment for age, daily cigarette consumption, body mass index, ethanol consumption, and percentage of calories obtained from fat.

Adult↗

PubMed1983

Uptake of [35S]sulphate in human colonic mucosa associated with carcinoma: an autoradiographic analysis at the ultrastructural level.

The uptake of [35S]sodium sulphate, as a sulphomucin precursor, was studied at the ultrastructural level as part of our investigation into alterations in glycoprotein synthesis occurring in colonic mucosa adjacent to carcinoma ('transitional' mucosa). The sulphate labelling was analysed statistically after incorporation and pulse labelling studies to show the amount of uptake into cellular organelles and the rate of transport through the cells. Uptake studies showed the following changes in the 'transitional' mucosa as compared with normal mucosa. (1) In the middle crypt, sulphate incorporation from the Golgi apparatus into the mucin droplets of the goblet cells was reduced in contrast with an increased uptake into the vesicles of the absorptive and 'intermediate' cells. (2) In the upper crypt, more sulphate was incorporated in the goblet cells. These results correlate well with previous histochemical findings of a larger proportion of sulphomucins in the vesicles of columnar cells and a predominance of sialomucins in the goblet cells in the colonic mucosa associated with carcinoma. The pulse labelling studies revealed that in the middle crypt region of the 'transitional' mucosa, the rate of movement of label was faster through the Golgi body but less labelling was reaching the mucin droplets. The data suggest that either an inadequate supply of acceptor molecules was available at the Golgi level or a blockage in the attachment mechanism of the free sulphate to the completing glycoproteins was occurring at this level. Alternatively both mechanisms may be operating simultaneously.

Autoradiography↗

PubMed2001

[Colonic aganglionosis with ileal involvement. Ileocolic plasty].

During 1994 through 1999, we have treated five patients (3 boys, 2 girls) with total colonic aganglionosis (TCA) and ileal involvement. In three of them we performed a diverting ileostomy in the neonatal period and at the age of four and five months respectively in the remaining two patients, due to intestinal obstruction. In these two last patients a diagnosis of Hirschsprung's disease was made by anorectal manometry and rectal biopsies in the neonatal period. During laparotomy, a cutaneous ileostomy was created in all patients at the distal end of normal ileum, which was 30 to 110 cm (mean = 71 +/- 37 cm) from the ileocecal valve. After operation, a short bowel syndrome developed in three patients causing fluid and nutritional problems that required prolonged total parenteral nutrition (TPN). The definitive operative repair is performed at 4.5 to 14 months (mean = 8 +/- 3.7 months) by a 12 to 20 cm side-to-side ileocolostomy created between the ileum and aganglionic ascending color (Boley procedure) and ileorectal primary anastomosis (Rehbein procedure) using a circular stapler. Rectal dilatation, irrigation of the colon with saline, loperamide hydrochloride and resincholestyramine were begun in all patients postoperatively. Oral antibiotic prophylaxis, was given to the three patients who suffered from SBS. Oral feedings with semielemental diet were tolerated once stools were semiformed and TPN was discontinued at 8 to 34 days (mean = 21 +/- 1.7 days). postoperatively. After the definitive operation, enterocolitis developed in two patients, requiring one of them a short hospitalization during the episode. A possible explanation for the low incidence of enterocolitis in this series is the systematic postoperative use of irrigations of the colon with saline in all patients. These five patients have been followed-up for growth, development, bowel habit and continence. Follow-up has ranged from 15 to 62 months (mean = 32.2 +/- 19.2 months). Presently, all patients in this series have full enteral feeding and one to three bowel movements per day, with formed or semiformed stools. No patients is incontinent of stool. The patient's body weights (74 to 93%) and heights (89 to 92%) for their age were below average (four patients) or within normal range (one patient). Hemoglobin levels are within normal range in all patients. One patient has iron deficiency and another one has serum ferritin concentration below normal. Three patients have folic acid deficiency. Vitamin B12 absorption is normal in all patients. Although we can not conclude this is a better procedure than others, with is use we have obtained satisfactory results, with an excellent survival, scanty morbidity, a rapid return of bowel function and continence, and an acceptable physical development. During long-term follow-up, patients mus be evaluated for iron and folic acid deficiency.

Child↗

PubMed1998

Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery. A randomised, double-blind, cross-over study with and without adrenaline.

BACKGROUND: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. METHODS: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml.h-1 of bupivacaine 1 mg.ml-1, fentanyl 2 micrograms.ml-1, and adrenaline 2 micrograms.ml-1 were included. On the 1st and 2nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. RESULTS: The number of hypaesthetic dermatomal segments decreased (P < 0.001) and pain intensity at rest and when coughing increased (P < 0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15-20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng.ml-1 (P < 0.01), and there was more sedation during the period without adrenaline. CONCLUSIONS: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Theophylline. A "state of the art" review.

Theophylline is a bronchodilator and respiratory stimulant that is effective in the treatment of acute and chronic asthma, Cheyne-Stokes respirations, and apnea/bradycardia episodes in newborns. It is also used as an adjunct in the treatment of congestive heart failure and acute pulmonary edema, but it has no established efficacy in patients with chronic irreversible airways obstruction. Benefits and risks from theophylline relate directly to serum concentration, which is a function of both dose and elimination characteristics of the drug in an individual patient. When used to treat acute symptoms, an initial loading dose based on a mean volume of distribution is required to rapidly obtain maximum bronchodilator effect. Because of large interpatient differences in elimination, constant intravenous infusion rates for continued therapy must be guided by monitoring serum theophylline concentration at intervals until a steady-state serum concentration is reached within the 10-20 micrograms/ml therapeutic range. Intravenous, oral or rectal solutions and plain uncoated tablets are appropriate for acute therapy, while reliably absorbed slow-release formulations offer therapeutic advantages for the management of chronic asthma, particularly in patients with rapid elimination. Dosage for long-term therapy is determined by starting with low doses that allow virtually complete acceptance of the medication followed by gradual increases, if tolerated, at three day intervals until mean age-specific doses are reached. Subsequent adjustment in dosage regimens are then based upon serum concentration measurements. Most clinical laboratories now measure theophylline, and newer systems have been developed to provide emergency results within minutes at a reasonable cost. In cases of theophylline poisoning, the drug must be rapidly removed to prevent life-threatening toxicity. When serum concentrations are in excess of 60 micrograms/ml charcoal hemoperfusion dialysis may be indicated, even in the absence of obvious signs of toxicity.

Absorption↗

PubMed1983

Enhancement of lymphatic transport of 1-(2-tetrahydrofuryl)-5-fluorouracil by polyacrylic acid aqueous gel and emulsion type suppositories in rats.

1-(2-Tetrahydrofuryl)-5-fluorouracil (FT-207) concentrations in lymph and plasma were measured after rectal administration of three types of suppositories containing FT-207. The suppositories used in this study were prepared from polyacrylic acid aqueous gel bases, emulsion type bases and a commercial fat base, witepsol w-35. Both aqueous gel and emulsion type suppositories were superior to the suppositories from witepsol with regard to FT-207 concentration in lymph and plasma. The addition of aqueous gel to the polyacrylic acid aqueous gel was found to be effective for the lymph transport from the aqueous gels. Polyacrylic acid aqueous gel containing 1% glycyrrhizin was better than other suppositories. Solidification of the emulsion type bases are also investigated, and it is suggested that these may be better substitutes of the oily suppository.

Acrylic Resins↗

PubMed1998

Clinical pharmacokinetics of nimesulide.

Nimesulide is a selective COX-2 inhibitor used in a variety of inflammatory, pain and fever states. After healthy volunteers received oral nimesulide 100 mg in tablet, granule or suspension form the drug was rapidly and extensively absorbed. Mean peak concentrations (Cmax) of 2.86 to 6.50 mg/L were achieved within 1.22 to 2.75 hours of administration. The presence of food did not reduce either the rate or extent of nimesulide absorption. When nimesulide was administered in the suppository form, the Cmax was lower and occurred later than after oral administration; the bioavailability of nimesulide via suppository ranged from 54 to 64%, relative to that of orally administered formulations. Nimesulide is rapidly distributed and has an apparent volume of distribution ranging between 0.18 and 0.39 L/kg. It is extensively bound to albumin; the unbound fraction in plasma was 1%. The unbound fraction increased to 2 and 4% in patients with renal or hepatic insufficiency. With oral administration, the concentrations of nimesulide declined monoexponentially following Cmax. The estimated mean terminal elimination half-life varied from 1.80 to 4.73 hours. Excretion of the unchanged drug in urine and faeces is negligible. Nimesulide is largely eliminated via metabolic transformation and the principal metabolite is the 4'-hydroxy derivative (M1). Minor metabolites have been detected in urine and faeces, mainly in a conjugated form. Pharmacological tests in vivo have shown that the metabolites are endowed with anti-inflammatory and analgesic properties, although their activity is lower than that of nimesulide. Excretion in the urine and faeces accounted for 50.5 to 62.5% and 17.9 to 36.2% of an orally administered dose, respectively. The total plasma clearance of nimesulide, was 31.02 to 106.16 ml/h/kg, reflecting almost exclusive metabolic clearance. The drug has a low extraction ratio, close to 0.1. With twice daily oral or rectal administration of nimesulide, steady-state was achieved within 24 to 48 hours (2 to 4 administrations); only modest accumulation of nimesulide and M1 occurred. Gender has only a limited influence on the pharmacokinetic profiles of nimesulide and M1. The pharmacokinetic profiles of nimesulide and M1 in children and the elderly did not differ from that of healthy young individuals. Hepatic insufficiency affected the pharmacokinetics of nimesulide and M1 to a significant extent: the rate of elimination of nimesulide and M1 was remarkably reduced in comparison to the rate of elimination in healthy individuals. Therefore, a dose reduction (4 to 5 times) is required in patients with hepatic impairment. The pharmacokinetic profile of nimesulide and M1 was not altered in patients with moderate renal failure and no dose adjustment in patients with creatinine clearances higher than 1.8 L/h is envisaged. Pharmacokinetic interactions between nimesulide and other drugs given in combination [i.e. glibenclamide, cimetidine, antacids, furosemide (frusemide), theophylline, warfarin and digoxin] were absent, or of no apparent clinical relevance.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1995

Primary structure, functional expression, and chromosomal localization of the bumetanide-sensitive Na-K-Cl cotransporter in human colon.

By moving chloride into epithelial cells, the Na-K-Cl cotransporter aids transcellular movement of chloride across both secretory and absorptive epithelia. Using cDNA probes from the recently identified elasmobranch secretory Na-K-Cl cotransporter (sNKCC1) (Xu, J. C., Lytle, C. Zhu, T. T., Payne, J. A., Benz, E., and Forbush, B., III (1994) Proc. Natl. Acad. Sci. 91, 2201-2205), we have identified the human homologue. By screening cDNA libraries of a human colonic carcinoma line, T84 cell, we identified a sequence of 4115 bases from overlapping clones. The deduced protein is 1212 amino acids in length, and analysis of the primary structure indicates 12 transmembrane segments. The primary structure is 74% identical to sNKCC1, 91% identical to a mouse Na-K-Cl cotransporter (mNKCC1), 58% identical to rabbit and rat renal Na-K-Cl cotransporters (NKCC2), and 43% identical to the thiazide-sensitive Na-Cl cotransporters from flounder urinary bladder and rat kidney. Similar to sNKCC1 and mNKCC1, the 5'-end of the human colonic cotransporter is rich in G + C content. Interestingly, a triple repeat (GCG)7 occurs within the 5'-coding region and contributes to a large alanine repeat (Ala15). Two sites for N-linked glycosylation are predicted on an extracellular loop between putative transmembrane segments 7 and 8. A single potential site for phosphorylation by protein kinase A is present in the predicted cytoplasmic C-terminal domain. Northern blot analysis revealed a 7.4-7.5-kilobase transcript in T84 cells and shark rectal gland and a approximately 7.2-kilobase transcript in mammalian colon, kidney, lung, and stomach. Metaphase spreads from lymphocytes were probed with biotin-labeled cDNA and avidin fluorescein (the cotransporter gene was localized to human chromosome 5 at position 5q23.3). Human embryonic kidney cells stably transfected with the full-length cDNA expressed a approximately 170-kDa protein recognized by anti-cotransporter antibodies. Following treatment with N-glycosidase F, the molecular mass of the expressed protein was similar to that predicted for the core protein from the cDNA sequence (132-kDa) and identical to that of deglycosylated T84 cotransporter (approximately 135-kDa). The stably transfected cells exhibited a approximately 15-fold greater bumetanide-sensitive 86Rb influx than control cells, and this flux required external sodium and chloride. Flux kinetics were consistent with an electroneutral cotransport of 1Na:1K:2Cl. Preincubation in chloride-free media was necessary to activate fully the expressed cotransporter, suggesting a [Cl]-dependent regulatory mechanism.

Amino Acid Sequence↗

PubMed1986

Two-dimensional characterization of prostatic acid phosphatase, prostatic specific antigen and prostate binding protein in expressed prostatic fluid.

Specimens of pooled prostatic fluid, collected by rectal massage from men under 50 years of age with no apparent prostatic disorders, were subjected to two-dimensional gel electrophoresis to study the composition of its proteins. In a preliminary study, a total of 57 major protein groups were detected. In the present study, we attempted to identify, in the two-dimensional gels, those that are related to prostate-associated proteins, i.e., prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), and prostate binding protein (PBP). Individual proteins were recognized by the procedure of Western Blot using specific antisera with peroxidase-antiperoxidase as the staining reagent. Each protein spot in the two-dimensional gel was expressed, along the abscissa, by its isoelectric point (pI) and, along the ordinate, by the molecular weight (MW). PAP consisted of a train of more than ten protein spots that occupied an area in the gel from pI 7.0, MW 45,000 to pI 6.0, MW 50,000. Four protein spots with a MW of 34,000 and a pI range of 8.2-8.8 were identified as PSA. PBP was observed as having three protein spots that were located at pI 5.6-6.6 with a single MW of 15,000. For PAP and PSA, additional protein spots with lower MWs also stained positively with the specific antisera, suggestive of the presence of degradative products of these proteins. Following the removal of the serum-related proteins by an extensive absorption with anti-human serum antibody by affinity chromatography, the prostatic fluid contained 27 major groups of non-serum proteins. These non-serum proteins in the prostatic fluid included PAP, PSA, PBP, and their related smaller molecular species. These results indicate that the prostatic fluid contains PAP, PSA, PBP and that their presence and the patterns of their distribution in the two-dimensional gels should be considered as the characteristic property of the prostatic secretions.

Acid Phosphatase↗

PubMed1986

The clinical significance of gastrointestinal helminths--a review.

Gastrointestinal helminths (nematodes, trematodes and cestodes) constitute some of the most common and important infective agents of mankind and are responsible for much morbidity and some mortality. Whereas many symptoms and signs are confined to the intestine and less often the associated digestive organs, systemic manifestations are also numerous; this applies especially to indigenous populations of developing 'Third World' countries. Using a clinical classification these organisms can be broadly separated into those involving the small-intestine and those which have a colo-rectal distribution; of the former, a minority has been causally related to intestinal malabsorption. Clearly, however, not all gastrointestinal helminths are associated with disease and it is important to be able to separate these two groups; when present at high concentration and especially in infants and children some of the least pathogenic are not, however, entirely asymptomatic. Maintenance of a high 'index of suspicion' is necessary and this applied especially to 'western' populations in whom rapid and extensive travel to areas of the world with substandard sanitation and contaminated food and water supplies is now common; first evidence of infection in them may result from serious clinical complications. Recent advances have focussed on treatment, and especially the introduction of the benzimidazole compounds (especially albendazole) for nematode, and praziquantel for cestode, infections. Treatment of strongyloidiasis remains, however, unsatisfactory. Mass elimination of gastrointestinal helminths in developing 'Third World' countries remains a major challenge.

Adult↗

PubMed2005

Bioavailability and safety of a high dose of docosahexaenoic acid triacylglycerol of algal origin in cystic fibrosis patients: a randomized, controlled study.

OBJECTIVE: Several studies have reported omega-3 and omega-6 fatty acid imbalances in patients with cystic fibrosis (CF). Whether these imbalances contribute to or are manifestations of the pathophysiology of CF is unknown. The study objective was to determine bioavailability, tissue accretion, and safety of a large dose of an algal source of docosahexaenoic acid (DHA) triacylglycerol and to observe effects on lung function in patients with CF. METHODS: Twenty subjects with CF (8 to 20 y of age) were randomly assigned to receive algal oil providing 50 mg of DHA per kilogram per day (1 to 4.2 g of DHA per subject per day) or placebo for 6 mo. Fatty acids, liver enzymes, and lipid soluble antioxidants were measured in blood at baseline and at 1, 3, and 6 mo. Rectal biopsy specimens were collected at baseline and at 3 mo for fatty acid analysis. Lung function, anthropometrics, and adverse experiences were monitored throughout the study. RESULTS: Compared with placebo, DHA supplementation increased plasma, erythrocyte, and rectal DHA levels four- to five-fold (P < 0.001) with concomitant decreases in blood arachidonic acid levels and the ratio of arachidonic acid to DHA. Supplementation was well tolerated, with no treatment-related changes in liver enzymes, growth, or antioxidant status. DHA supplementation had no detectable effect on lung function during the course of this study. CONCLUSIONS: Algal DHA triacylglycerol oil is readily absorbed, well tolerated, and increases blood and tissue DHA levels in patients with CF. No adverse developments were associated with this large dose of DHA oil. Larger studies of longer duration are needed to determine whether DHA supplementation results in any clinically significant benefits in patients with CF.

Adolescent↗

PubMed2000

Clinical evaluation and verification of the hyperthermia treatment planning system hyperplan.

PURPOSE: A prototype of the hyperthermia treatment planning system (HTPS) HyperPlan for the SIGMA-60 applicator (BSD Medical Corp., Salt Lake City, Utah, USA) has been evaluated with respect to clinical practicability and correctness. MATERIALS AND METHODS: HyperPlan modules extract tissue boundaries from computed tomography (CT) images to generate regular and tetrahedral grids as patient models, to calculate electric field (E-field) distributions, and to visualize three-dimensional data sets. The finite difference time-domain (FDTD) method is applied to calculate the specific absorption rate (SAR) inside the patient. Temperature distributions are calculated by a finite-element code and can be optimized. HyperPlan was tested on 6 patients with pelvic tumors. For verification, measured SAR values were compared with calculated SAR values. Furthermore, intracorporeal E-field scans were performed and compared with calculated profiles. RESULTS: The HTPS can be applied under clinical conditions. Measured absolute SAR (in W/kg), as well as relative E-field scans, correlated well with calculated values (+/-20%) using the contour-based FDTD method. Values calculated by applying the FDTD method directly on the voxel (CT) grid, were less well correlated with measured data. CONCLUSION: The HyperPlan system proved to be clinically feasible, and the results were quantitatively and qualitatively verified for the contour-based FDTD method.

Algorithms↗