Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Charcot neuroarthropathy is one of the most devastating complications of diabetes causing much discomfort and disability and sometimes leading to amputation. The current therapies are disappointing and fail to address the underlying disease process. In order to try and halt the underlying bone resorption we have studied the action of the bisphosphonate, pamidronate, in six diabetic patients with active Charcot neuroarthropathy. The treatment was associated with improvement in the patients' symptoms and a reduction in Charcot activity as measured by temperature of the affected foot which fell from 3.4 +/- 0.7 (SE) degrees C to 1.0 +/- 0.5 degrees C above the intact foot (p = 0.05). There was a significant reduction in bone turnover as judged by alkaline phosphatase activity which fell by 25 +/- 3% (p < 0.001). These preliminary data suggest that bisphosphonates may be the first definitive treatment for active Charcot neuroarthropathy and that controlled trials are now indicated.
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PMID:Bisphosphonates: a new treatment for diabetic Charcot neuroarthropathy? 818 Dec 48

Functional dyspepsia (FD) includes a heterogeneous group of patients suffering from a variety of different conditions. The Dyspepsia Project has been implemented in 14 GI Units since 1984, in order to epidemiologically test the discriminating power of the Working Teams definitions and of standardized questionnaires. Five per cent of admitted subjects were subclassified as sphincter of Oddi dysfunction or biliary dyspepsia (BD), defined as biliary pain associated or not to bilirubin or alkaline phosphatase elevation, in the abscence of ultrasonographic evidence of gallstone disease or bile duct dilatation. The more useful symptoms in favour of the diagnosis of biliary dyspepsia were found to be pain in the right hypochondrium, radiating to the shoulder, or to the back, initiated by food, and eventually associated with constipation, or epigastric postprandial discomfort. Interestingly, symptoms suggesting biliary dyspepsia are partially shared by dysmotility-like dyspepsia. The placebo response in functional dyspepsia is variable, between 6 and 80% of patients, reflecting variations in the kind and severity of the diseases in different studies. That represents a considerable difficulty in evaluating drug efficacy, even in the case of biliary dyspepsia. A therapeutic double-blind trial in functional dyspepsia using tauro-ursodeoxycholic acid is discussed.
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PMID:Functional dyspepsia: how could a biliary dyspepsia sub-group be recognized? A methodological approach. 884 44

The current study aimed to apply a novel enhanced chemiluminescence assay in the analysis of gingival crevicular fluid (GCF) alkaline phosphatase (ALP) levels from patients with untreated adult periodontitis. 3666 sites in 25 patients were monitored prior to and after attachment loss was detected with a Florida disc probe. Parameters assessed were, relative attachment level, probing pocket depth, occurrence of bleeding on probing (single episode), GCF volume (microliter), total ALP levels (microIU/30 s sample time) and ALP concentration (IU/l). After recruiting patients to the study, all measures were taken at baseline and 3 months later, prior to the institution of non-surgical periodontal therapy at active sites. Thresholds for determining attachment loss were calculated using a modification of the tolerance method. The mesio-buccal sites of all teeth had GCF samples collected. The size of individual patient thresholds used to define whether attachment loss had occurred, was dependent upon the discomfort felt by that patient during electronic probing, with a positive correlation existing between discomfort on probing (10 cm visual analogue scale) and threshold size (R = 0.52, p < 0.049). A total of 274 sites (7.5%) experienced attachment loss of which 39 sites had GCF samples available for analysis. Total ALP levels were significantly higher at baseline for sites that progressed to attachment loss than paired controls (p < 0.003), but all other parameters showed no differences (p > 0.1). There were significant increases in total ALP levels and GCF volumes for active sites between baseline and 3 month measures (p < 0.01), but not for control sites or test site ALP concentration (p > 0.8). The diagnostic accuracy for GCF ALP as a predictor of future attachment loss (threshold 900 microIU/30 s) was 64%, with +ve and -ve predictive values of 62% and 68%. When a threshold of 1300 microIU/30 s was selected for ALP as a marker of recent or currently active disease, diagnostic accuracy and +ve/-ve predictive values were 77% and 77%/76%, respectively. These results indicate that total GCF ALP levels may serve as a predictor of future or current disease activity.
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PMID:Prediction and diagnosis of attachment loss by enhanced chemiluminescent assay of crevicular fluid alkaline phosphatase levels. 1010 46

One of the aims of the treatment of Paget's disease with bisphosphonates should be the normalization of the activity of the disease with the shortest possible exposure to the drug. Olpadronate (OPD) is a new bisphosphonate characterized by the dimethylation of the amino group, its potency is near to alendronate, and more soluble in the digestive media than other aminobisphosphonates. We treated 46 patients (28 men and 18 women, mean age 70 years) with active Paget's disease with oral OPD, 200 mg/day for 12 +/- 2 days, except 2 patients who received 400 mg/day. Eight patients had never been treated before, and 38 had previously received antiosteolytic drugs. The period without treatment prior to OPD was (X +/- 1 SD) 14 +/- 12 months. Baseline bone alkaline phosphatase (BALP) (levels fell from (X +/- 1 SD) 54.0 +/- 62.7 IU/ml (range 22-396) to a lowest mean value of 16.2 +/- 6.4 IU/ml (range 8-45) (normal range 5-21 IU/ml). Forty patients normalized BALP values, in most of the cases within the first 3 months after OPD treatment. Two patients showed partial response (> 50% decrease from baseline), three patients presented poor response (< 50% decrease from baseline), and one patient did not respond at all. Two patients complained of gastric discomfort, and one patient had diarrhea, which disappeared after discontinuation of the drug. Follow-up was carried out on 36 patients; 22 patients are still in remission, with an average length of 9.0 +/- 2.6 months. Fourteen patients experienced relapse after 9 +/- 2 months remission. In conclusion, a 12-day treatment with 200 mg/day of OPD proved to be a very effective and well tolerated therapy of Paget's disease and induced biochemical remissions in the vast majority of patients, even in those with very active disease.
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PMID:Short-term therapy with oral olpadronate in active Paget's disease of bone. 1062 63

Autoimmune cholangitis is characterized biochemically by chronic cholestasis and histopathologically by chronic non-suppurative destructive cholangitis. It is associated with positive antinuclear antibody test and negative antimitochondrial antibody test results. Recently, we experienced a case of a 35-year-old woman with autoimmune cholangitis associated with thymoma who presented with pruritus, jaundice, chronic fatigue and anterior chest discomfort. Her laboratory examinations revealed marked increases in levels of serum alkaline phosphatase and gamma-glutamyl transpeptidase. In serological tests, antinuclear antibody was found, but antimitochondrial antibody was not. Liver biopsy findings were compatible with chronic non-suppurative destructive cholangitis. On computed tomography (CT) of the chest, a large anterior mediastinal mass was found. The mass was totally resected and the patient was treated with ursodeoxy cholic acid. Thereafter, her clinical symptoms improved and liver functions completely returned to the normal range. We describe here an uncommon association of autoimmune cholangitis with thymoma, which has not been reported previously in the English-written literature.
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PMID:Autoimmune cholangitis in a patient with thymoma. 1548 46

Adult bone marrow contains mesenchymal stem cells (bone marrow-derived mesenchymal stem cells; BMSCs) which contribute to the generation of mesenchymal tissue such as bone, cartilage, muscle and adipose. However, using bone marrow as a source of stem cells has the limitation of a low cell number. An alternate source of adult stem cells that could be obtained in large quantities, under local anesthesia, with minimal discomfort would be advantageous. Human adipose tissue obtained by liposuction was processed to obtain a fibroblast-like population of cells or adipose tissue-derived stromal cells (ATSCs). In this study, we compared the osteogenic differentiation of ATSCs with that of BMSCs. Both cell types were cultured in atelocollagen honeycomb-shaped scaffolds with a membrane seal (ACHMS scaffold) for three-dimensional culturing in a specific osteogenic induction medium. Optimal osteogenic differentiation in both cell types, as determined by alkaline phosphatase cytochemistry, secretion of osteocalcin, mineral (calcium phosphate) deposition and scanning electron microscopy, was obtained with the same three-dimensional culture. Furthermore, osteoblastic lining in vivo was examined using ATSC-seeded or BMSC-seeded scaffolds in nude mice. The present results show that ATSCs have a similar ability to differentiate into osteoblasts to that of BMSCs.
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PMID:Osteogenic potential of human adipose tissue-derived stromal cells as an alternative stem cell source. 1555 Jul 55

Scrub typhus is an acute febrile illness caused by Orientia induced vasculitis, which is common in Asia and the Pacific Islands and is sometimes also encountered in Western countries. Even though it can cause multi-organ dysfunctions, there is limited information regarding the relationship between scrub typhus infection and gastrointestinal dysfunction. Therefore, a cross-sectional study was conducted to discover the gastrointestinal manifestations of septic patients with scrub typhus infection. During the study period, 80 septic cases were recruited, and according to the results of immunofluorescent antibody testing (IFA), 20 (25%) were found to have scrub typhus infection. The most common gastrointestinal symptoms of scrub typhus patients were vomiting 13 (65%), nausea 12 (60%), diarrhea 9 (45%), and hametamesis or melena 5 (25%). Gastrointestinal signs included hepatomegaly 8 (40%), jaundice 7 (35%), and abdominal pain 4 (20%). Elevation of SGOT, SGPT, and alkaline phosphatase were 16 (80%), 14 (70%), and 16 (80%), respectively. Direct bilirubin was elevated in 19 (95%) of the cases and half of the cases had a low serum protein level. Of scrub typhus cases, 8 (40%) had eschars. The sites of eschars were mostly in hidden areas, such as on the back, genitalia and abdomen. Three of the five patients with eschar had hepatomegaly on ultrasound examination. The significant findings of the scrub typhus septic patients with eschar on endoscopic examination were gastritis in two cases, gastritis with gastric erosion in two cases, and one case showed a duodenal ulcer and erosion. The differentiating point for endoscopic findings in scrub typhus compared to the other causes was that the stomach lesions were more frequent and severe than the duodenal lesions. According to our endoscopic findings, physicians should be aware of gastric and duodenal lesions in febrile patients with gastrointestinal symptoms, such as abdominal pain or discomfort and indigestion. Scrub typhus can cause gastrointestinal and liver dysfunction.
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PMID:Gastrointestinal manifestations of septic patients with scrub typhus in Maharat Nakhon Ratchasima Hospital. 1591 79

There is a need for new therapeutic strategies to treat bone defects caused by trauma, disease or tissue loss. Injectable systems for cell transplantation have the advantage of allowing the use of minimally invasive surgical procedures, and thus for less discomfort to patients. In the present study, it is hypothesized that Arg-Gly-Asp (RGD)-coupled in a binary (low and high molecular weight) injectable alginate composition is able to influence bone cell differentiation in a three-dimensional (3D) structure. Viability, metabolic activity, cytoskeleton organization, ultrastructure and differentiation (alkaline phosphatase (ALP), von Kossa, alizarin red stainings and osteocalcin quantification) of immobilized cells were assessed. Cells within RGD-modified alginate microspheres were able to establish more interactions with the synthetic extracellular matrix as visualized by confocal laser scanning microscope and transmission electron microscopy imaging, and presented a much higher level of differentiation (more intense ALP and mineralization stainings and higher levels of osteocalcin secretion) when compared to cells immobilized within unmodified alginate microspheres. These findings demonstrate that peptides covalently coupled to alginate were efficient in influencing cell behavior within this 3D system, and may provide adequate preparation of osteoblasts for cell transplantation.
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PMID:Upregulation of bone cell differentiation through immobilization within a synthetic extracellular matrix. 1753 40

Persistent hyperparathyroidism is the most frequent cause of hypercalcemia after renal transplantation, namely, hypercalcemia is observed in about 10% of patients at 1 year. This prospective study evaluated the effect of cinacalcet, a second-generation calcimimetic, on serum calcium and parathyroid hormone (PTH) blood levels among recipients with hypercalcemia due to persistent hyperparathyroidism. Thirteen renal transplanted patients (10 women and 3 men) were included based upon: a total serum calcium >10.5 mg/dL; intact PTH (iPTH) blood levels >65 pg/mL; graft function >6 months, and stable maintenance immunosuppressive therapy. After inclusion, patients initially received 30 mg of cinacalcet once daily. The mean time of initiation was 64 +/- 7 months after transplantation. The follow-up was 6 months. The median dose of cinacalcet was 30 mg/d (5 patients received 60 mg/d). During the study period, renal function remained stable. Serum calcium levels decreased significantly from 11.7 +/- 0.39 to 10.35 +/- 0.8 mg/dL (P < .001). Serum phosphate levels increased from 2.82 +/- 0.34 mg/dL to 3.2 +/- 0.41 mg/dL (P < .05). The mean iPTH levels significantly decreased from 308 +/- 120 to 210 +/- 80 pg/mL (P < .05). There were no significant change in 25-hydroxyvitamin D3 blood levels (from 17.7 +/- 9 to 17.4 +/- 6 ng/mL), but the 1,25-dihydroxyvitamin D3 blood levels decreased from 53.8 +/- 18.2 to 32.6 +/- 9.2 pg/mL (P < .01). There were no significant changes in blood levels of alkaline phosphatase, magnesium, bicarbonate, calciuria, phosphaturia, and immunosuppressive drugs. Cinacalcet was well tolerated in all patients except one who had gastrointestinal discomfort. In summary, cinacalcet corrected hypercalcemia and improved phosphatemia in patients with persistent hyperparathyroidism after transplantation with no negative effects on renal function.
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PMID:Cinacalcet for the treatment of hypercalcemia in renal transplanted patients with secondary hyperparathyroidism. 1788 55

Methoxyisopropanol and Methoxyisopropyl Acetate, commonly known as propylene glycol monomethyl ether (PGME) and propylene glycol monomethyl ether acetate (PGMEA), respectively, have fragrance, solvent, and viscosity-decreasing functions in cosmetics, although only Methoxyisopropanol is in current use at concentrations ranging from 4% to 35%. Methoxyisopropanol is easily absorbed into the bloodstream upon inhalation or ingestion. The acetate ester is readily metabolized to Methoxyisopropanol in the body, which is excreted unchanged in the expired breath or in the urine as free or conjugated Methoxyisopropanol, or as the primary metabolite propylene glycol. In acute oral toxicity studies, the LD(50) values of Methoxyisopropanol were 4.6 to 9.2 g/kg in rats, with similar low acute toxicity in other animal species. Inhalation exposures of rats, mice, and rabbits to 3000 ppm Methoxyisopropanol for 6 h per day for 9 days to 13 weeks produced increased relative liver weights, signs of central nervous system (CNS) depression, and in some cases, elevated serum alkaline phosphatase, alanine aminotransferase, or hepatocellular hypertrophy, but the kidneys were unaffected. The no observed adverse effect level (NOAEL) for 13-week inhalation exposures to Methoxyisopropanol was 1000 ppm in rats and rabbits. In a 90-day dermal exposure study using rabbits, 10 ml/kg undiluted Methoxyisopropanol produced narcosis and increased kidney weights and the NOAEL was 7.0 ml/kg. Chronic (2-year) daily inhalation exposures of rats and mice to 3000 ppm Methoxyisopropanol produced signs of liver toxicity (rats and mice) and some evidence of renal toxicity in rats. The only observation at 1000 ppm was dark foci of the liver in male rats. For female rats and male and female mice, the NOAEL of this chronic inhalation study was 1000 ppm Methoxyisopropanol. Methoxyisopropanol and Methoxyisopropyl Acetate were found to be nonirritating to slightly irritating and non-sensitizing in rabbit and guinea pig skin. Repeated applications of undiluted Methoxyisopropanol to the eyes of rabbits produced transient slight to moderate irritation. Pregnant rats exposed to 200 or 600 ppm Methoxyisopropanol by inhalation on gestation days 6 to 17 had no effects on maternal health or normal fetal development. Adult male rats exposed to these concentrations had no effects on the reproductive organs. Pregnant rats and rabbits exposed to 500 to 3000 ppm Methoxyisopropanol by inhalation during gestation had no significant embryotoxic or fetotoxic effects, althougth CNS depression and reduced body weight gain were observed in the 3000 ppm group. In a two-generation inhalation study using rats, continuous inhalation of 3000 ppm Methoxyisopropanol produced CNS depression, prolonged estrous cycles, reduced fertility indices, reduced pup weights and pup survival, and delayed sexual development, with a NOAEL for reproductive and developmental effects of 1000 ppm. In a continuous breeding protocol using mice, 2.0% Methoxyisopropanol in drinking water produced reduced growth, reduced relative epididymis weight, reduced relative prostate weight, and increased liver weight (females only) in offspring, with a NOAEL at a 1% concentration. Exposure of mice or rats to 300 ppm to 3000 ppm Methoxyisopropanol by inhalation produced no signs of carcinogenicity. Methoxyisopropanol was negative for mutagenicity or genetic toxicity in the bacterial reverse mutation assay (<or= 5000 microg/plate), the unscheduled DNA synthesis (UDS) assay (<or= 0.1 M), V79 Chinese hamster lung assay (>100 mM), and in the Siberian hamster embryo assay (concentrations not reported). In other assays, 100 mM Methoxyisopropanol increased sister chromatid exchanges in V79 cells. In human inhalation exposure studies of 1 to 7 h duration, 50 to 75 ppm Methoxyisopropanol vapor had an objectionable odor; 150 ppm was slightly irritating to the eyes and throat; 250 ppm produced eye irritation, lacrimation, blinking, rhinorrhea, and headache; 300 ppm was mildly irritating to the eyes, nose, and throat; 750 ppm was extremely irritating; and 2050 ppm produced extreme discomfort with severe lacrimation, blepharospasm, and painful breathing. None of the concentrations tested impaired motor coordination or performance on neurological tests. The irritating effects subsided within 15 min to 24 h of removal from the inhalation chamber. The National Institute of Occupational Safety and Health (NIOSH) recommended an 8-h time-weighted average for occupational exposure of 100 ppm. A margin of safety of 500 was determined, based on a calculated exposure from the normal use of nail polish remover products (100% absorption) and the NOAEL for reproductive toxicity. The absorption of Methoxyisopropanol through the nail is likely to be low, suggesting this margin of safety is conservative. Because Methoxyisopropanol is volatile, exposure by inhalation is possible, but the odor becomes objectionable at 50 to 75 ppm in air. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that Methoxyisopropanol and Methoxyisopropyl Acetate are safe for use in nail care products in the practices of use and concentration as described in this safety assessment.
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PMID:Final report on the safety assessment of methoxyisopropanol and methoxyisopropyl acetate as used in cosmetics. 1883 Aug 62


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