Biological effects of eleven combined oral contraceptives on serum triglycerides, gamma-glutamyltransferase, alkaline phosphatase, bilirubin and other biochemical variables

The objectives of this paper are to update and quantify the biological effects of the most commonly used oral contraceptives (OC) on 15 biochemical tests currently determined in clinical laboratories and to compare these effects between the different types of OC. The sample population was constituted by 1604 women using combined OCs and the control group comprised 3466 women in the same age range not taking medication. Women taking OC were divided into 11 groups according to the estrogen/progestogen combination. The effects of OCs were studied after adjustment for age, weight, height, body mass index and alcohol and tobacco consumption. The changes observed with the new progestogens were less important than in the past. In comparison with the controls, the mean serum triglyceride concentration was significantly increased by +8.5% to +36.0% (p<0.05 to p<0.001) in each group while those of total cholesterol and gamma-glutamyltransferase were increased only in 3 and 4 estrogen/progestogen combinations respectively. Conversely, the mean concentrations of alkaline phosphatase, total bilirubin, phosphate and albumin were significantly decreased. Using a discriminant analysis, three main groups according to the type of progestogen were defined: cyproterone acetate, DL-norgestrel and levonorgestrel, and all other progestogens. The changes in serum triglyceride concentration induced by OC intake must be considered by the clinician and are useful for taking a clinical and risk decision in an individual woman.     

Complexes in serum between alkaline phosphatase and immunoglobulin G: immunological and clinical aspects

A retrospective study was performed on 31 patients in whose sera an immune complex between alkaline phosphatase and immunoglobulin G had been detected. The average age of these patients was 64 years and the sexes were equally represented. Twenty-three patients (74%) had a disease with either an autoimmune aetiology or associated with circulating immune complexes or autoantibodies. Sera from 16 patients were tested for the presence of circulating immune complexes in addition to the alkaline phosphatase immune complex, and these complexes were detected in 14 cases (88%). Sera from 17 patients were tested for the presence of specific autoantibodies and these were detected in 9 cases (53%). Twelve patients were followed up for a mean period of 11.6 months (range 0.5 to 39 month). At the end of the follow-up period, 10 patients (83%) showed persistence of the immunoglobulin-G-alkaline phosphatase complex.     

Effect of stable strontium on the tissue alkaline and acid phosphatase activities of rat: feeding studies

The effect of feeding stable strontium (Sr) on the tissue alkaline and acid phosphatase activities was studied in young rats. These activities were reduced in liver and small intestine by 10% to 15% at 2 weeks, 20% to 30% at 4 weeks and in kidney by 20% at 6 weeks only in rats fed 2% Sr diet; bone alkaliine phosphatase activity was, however, increased by 80% to 100% (2-6 weeks) in these rats. Gross lesions like paralysis, hemorrhage, rickets and high mortality were observed after 4 to 6 weeks. Although no such lesions were seen, appreciable changes in enzyme activities as mentioned above were discernible in rats fed 1% Sr diet for 6 weeks. Feeding of a 0.5% Sr diet for a period up to 6 weeks had no deleterious effect. Recovery following consumption of a normal diet for 2 weeks was almost complete in liver and small intestine but not in kidney. The elevated tissue Sr levels do not explain the pronounced losses seen in this investigation as compared to those in the earlier in vitro experiments. This study depicts the possible damage due to prolonged therapeutic use of large amounts of stable Sr for the removal of radiostrontium.     

Serum total, heat and urea stable alkaline phosphatase activities in relation to ABO blood groups and secretor phenotypes

The relationship between serum alkaline phosphatase (AP) isoenzymes, ABO blood groups and secretor phenotypes was evaluated in 125 Nigerian voluntary blood donors. The serum total AP activity patterns were group O > Group B > Group AB > Group A, but only the differences between A/B, A/O and AB/O were significant. The total and activities of the different isoenzymes were lowest in group A, while highest values were found in group O. The different activities for group AB were intermediate between the levels for A and B. The activities of the different isoenzymes tended to be higher in secretors than in non-secretors. Our results may suggest that both the blood group and secretor genes are strong determinants of AP isoenzyme patterns in Nigeria.     

Analytical and clinical performance characteristics of Tandem-MP Ostase, a new immunoassay for serum bone alkaline phosphatase

The performance characteristics of the Tandem-MP Ostase assay, a new microplate immunoassay for bone-specific alkaline phosphatase (bone ALP; EC 3.1.3.1) in human sera, are described. Bone ALP is bound to streptavidin-coated microwells by a single biotinylated anti-bone ALP monoclonal antibody. Antigen is detected by the addition of p-nitrophenyl phosphate. The assay is performed at room temperature in <90 min. Imprecision was 2.3-6.1% with a detection limit of 0.6 microg/L. Method comparison of bone ALP measurements with the Tandem-MP Ostase assay and the mass-based Tandem-R Ostase assay (n = 285) indicated regression statistics of Tandem-MP Ostase = 1.03 Tandem-R Ostase + 0.22 microg/L, S(y/x) = 4.0 microg/L, r = 0.97. Serum bone ALP values in apparently healthy men and in pre- and postmenopausal women were also similar between the two Ostase assay formats. Liver ALP reactivity determined using the slope and heat inactivation methods was similar in both Ostase assays. Liver ALP reactivity ranged from 3 microg/L (heat inactivation) to 6 microg/L (slope method) per 100 U/L of liver ALP activity, whereas bone ALP reactivity was 37 microg/L per 100 U/L of bone ALP activity, indicating a liver ALP relative reactivity of 8.1-16.2%. Similar results were obtained with the Alkphase-B bone ALP immunoassay. The Tandem-MP Ostase bone ALP assay demonstrated increased concentrations of serum bone ALP in conditions where bone metabolism is increased and showed a rapid, temporal decrease in serum bone ALP in Paget disease patients on bisphosphonate therapy. In conclusion, the Tandem-MP Ostase assay for serum bone ALP is a rapid, simple, robust nonisotopic alternative to the Tandem-R Ostase immunoradiometric assay that provides an accurate and sensitive assessment of bone turnover.     

Age-specific modulation of light production potential, and alkaline phosphatase and protein tyrosine kinase activities in various age mutants of Caenorhabditis elegans

Previous work has shown that reduction-of-function mutations in the genes daf-2 and age-1 can increase adult life (Age phenotype) of Caenorhabditis elegans and that certain daf-12 alleles considerably amplify this effect in daf-2; daf-12 doubles. We have measured the light production potential (LPP) and alkaline phosphatase (ALP) and protein tyrosine kinase (PTK) activity levels as suitable biochemical markers to further investigate genetic interactions between these genes. The light production assay measures superoxide anion production by freeze-thawed worms in assay medium containing sufficient amounts of nicotineamide adenine dinucleotide, reduced form (NADH) and nicotineamide adenine dinucleotide phosphate, reduced form (NADPH) to drive the chemiluminescent reaction at maximal speed, and 5 mM cyanide to fully repress cytosolic superoxide dismutase (SOD). This assay thus provides an estimate of the maximum output of the metabolic pathways involved at the instant of freeze-fixation, and under the condition of the assay. LPP and PTK activities decreased similarly in daf-12(m20), and a control strain that had wild-type alleles of daf-12, age-1, and daf-2. The age-dependent decrease of LPP and PTK was reduced in age-1(hx542) and age-1(hx542); daf-2(e1370), and virtually absent in daf-2(e1370) and daf-2(e1370); daf-12(m20) mutant worms. ALP activity increased with age in non-Age genotypes and showed little, if any, age-dependent alteration in daf-2(e1370) and daf-2(e1370); daf-12(m20) mutant worms. Mutation in both age-1 and daf-2 caused no stronger phenotype than a single mutation as estimated by LPP, PTK, and ALP. We propose that (a) daf-2 is the major effector of metabolic activity during adult life, (b) daf-2 downregulates metabolic activity with increasing age, and (c) daf-12 stimulates oxygen consumption independently of daf-2.     

Thermal and pH stabilities of alkaline phosphatase from bovine intestinal mucosa: a FTIR study

The inactivation of alkaline phosphatase (AP) from bovine intestinal mucosa caused by lowering the p2H from 10.4 to 5.4 or by increasing the temperature from 25 degrees C to 70 degrees C were not followed by significant FTIR changes, indicating that the native conformation of AP was preserved under these conditions. Further decrease of p2H from 5.4 to 3.4 leaded to small infrared spectral changes of AP in the amide I' and amide II regions that were similar to the infrared spectral changes of AP induced by raising the temperature from 70 degrees C to 80 degrees C. The increase of temperature from 70 degrees C to 80 degrees C promoted the formation of intermolecular beta-sheets at the expense of some alpha-helix structures as evidenced by the appearance of the 1684 cm-1 and 1620 cm-1 component bands and the disappearance of the 1651-1657 cm-1 component band. This conformational change was followed by a sharp increase of the 2H/H exchange rate. CD spectra confirmed the FTIR results and were very sensitive to the variation of alpha-helix content while FTIR spectra were more receptive to the changes of beta-sheet structures.     

SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients

The authors analyzed the incidence of sexual dysfunction (SD) with different selective serotonin reuptake inhibitors (SSRIs; fluoxetine, fluvoxamine, paroxetine, and sertraline) and hence the qualitative and quantitative changes in SD throughout time in a prospective and multicenter study. Outpatients (192 women and 152 men; age = 39.6 +/- 11.4 years) under treatment with SSRIs were interviewed with an SD questionnaire designed for this purpose by the authors and that included questions about the following: decreased libido, delayed orgasm or anorgasmia, delayed ejaculation, inability to ejaculate, impotence, and general sexual satisfaction. Patients with the following criteria were included: normal sexual function before SSRI intake, exclusive treatment with SSRIs or treatment associated with benzodiazepines, previous heterosexual or self-erotic current sexual practices. Excluded were patients with previous sexual dysfunction, association of SSRIs with neuroleptics, recent hormone intake, and significant medical illnesses. There was a significant increase in the incidence of SD when physicians asked the patients direct questions (58%) versus when SD was spontaneously reported (14%). There were some significant differences among different SSRIs: paroxetine provoked more delay of orgasm or ejaculation and more impotence than fluvoxamine, fluoxetine and sertraline (chi 2, p < .05). Only 24.5% of the patients had a good tolerance of their sexual dysfunction. Twelve male patients who suffered from premature ejaculation before the treatment preferred to maintain delayed ejaculation, and their sexual satisfaction, and that of their partners, clearly improved. Sexual dysfunction was positively correlated with dose. Patients experienced substantial improvement in sexual function when the dose was diminished or the drug was withdrawn. Men showed more incidence of sexual dysfunction than women, but women's sexual dysfunction was more intense than men's. In only 5.8% of patients, the dysfunction disappeared completely within 6 months, but 81.4% showed no improvement at all by the end of this period. Twelve of 15 patients experienced total improvement when the treatment was changed to moclobemide (450-600 mg/day), and 3 of 5 patients improved when treatment was changed to amineptine (200 mg/day).     

Separation and quantification of corticosteroid-induced, bone and liver alkaline phosphatase isoenzymes in canine serum

Quantifying alkaline phosphatase (ALP) isoenzymes in canine serum would provide a useful index in a clinical laboratory. To achieve this goal, we tested a semi-automatic assay combining wheat germ lectin (WGL) precipitation and chemical inhibition of isoenzymes of the TNS gene with levamisole to quantify bone ALP (BALP) and corticosteroid-induced ALP (CALP), respectively. The liver ALP (LALP) isoenzyme was then calculated from the equation: TALP = BALP + LALP + CALP BALP, LALP and CALP standards from serum of puppies, bile-duct ligated dogs and dogs on 4.4 mg/kg/day prednisolone for 30 days, respectively, were used. The suitability of standard sera was tested by affinity electrophoresis. Levamisole (4.2 mM) inhibits 98% of BALP and LALP but only 42% CALP. Multiplying measured CALP by 1.8 gives the total CALP value in serum. WGL precipitated 92.3% BALP, 23.3% LALP and 26.8% heated CALP standards. These values were used to adjust precipitated ALP to obtain the exact levels of BALP. WGL was then tested on pooled serum standards in which the relative proportions of all the ALPs were known and controlled. BALP was adequately quantified except when LALP and CALP levels were extremely high. The assay was also applicable under conditions resulting in high ALP. Therefore, combining WGL and levamisole inhibition provides an adequate separation and quantification of canine ALP isoenzymes. The method has great potential for diagnostic use and should be tested further for routine implementation.     

Reactivation of alkaline phosphatase in ultra high-temperature, short-time processed liquid milk products

Alkaline phosphatase (enzyme) reactivation was studied in liquid milk products heated to 87.8 to 121.1 C for less than 1 s in a continuous, two-phase, slug-flow heat exchanger. The effects of magnesium concentration, pH, incubation temperature, homogenization pressure, processing temperature, fat content, and initial enzyme concentration were investigated. Jersey milk from one farm showed seasonal variations in enzyme concentration and its reactivation behavior. Increased reactivation in products with high fat content was due to high initial enzyme concentration in the product. Homogenization of products before heating decreased reactivation. Maximum reactivation occurred in products heated to 104.4 C, incubated at 34 C, and adjusted to pH 6.5. Maximum velocity of reactivation and reactivation constant varied with milk samples. Activation energy for the control and samples with magnesium was 22.646 +/- .118 and 24.100 +/- .210 kJ mole-1, respectively. The enzyme from raw and reactivated cream contained two major isozymes, and the reactivated isozyme differed from the control. The official method for differentiating residual and reactivated enzymes was modified in terms of magnesium concentration and extent of reactivation of the enzyme in the reactivated product.     

Construction, bacterial expression, and characterization of hapten-specific single-chain Fv and alkaline phosphatase fusion protein

Immature airways are highly compliant compared to the adult, suggesting that trachea and bronchi from immature animals may be easily compressed. Although tracheal compression has been extensively studied, the effect of transmural pressure on occlusion of immature bronchi has been neglected. The transmural pressure at which the lumen closed was determined from the transmittance of pressure along the lumen of isolated bronchi from late-term foetal, 1 and 4 week old pigs. Bronchi from eight cases of sudden infant death syndrome (SIDS) were also studied. In several experiments, smooth muscle tone was produced either by electrical field stimulation or carbachol challenge, and the relationship between active muscle tone and resting transmural pressure was studied. Bronchi from foetal, 1 and 4 week old pigs were occluded by intraluminal pressures of -4, -5 and -24 cmH2O. SIDS bronchi closed at -11 cmH2O. Histological and endoscopic investigations showed that closure of the bronchi occurred along a plane and was not uniform along the bronchus. Carbachol precontraction increased the transmural pressure required to close bronchi by approximately 5 cmH2O. The relationship between muscle tone and resting pressure was the same in all age groups, except when transmural pressure was at or below closing pressure. Bronchi from immature animals and human infants are vulnerable to collapse by small changes in transmural pressure. Bronchial closure is partly dependent on smooth muscle tone, particularly in younger animals.     

Histochemical studies of the development of alkaline and acid phosphatase activities in the ovary and oviduct of the fowl (Gallus domesticus)

Alkaline and acid phosphatase activities were studied in the ovary and oviducts of pullets from the age of 2-32 weeks. Adult fowls were similarly studied. Alkaline phosphatase activity was present only in the glandular grooves and crypts of the immature oviducts. Alkaline phosphatase activity appeared at the pits of epithelial evaginations as glandular formation commenced. The young, non-secreting glands also showed the enzyme activity. But in the mature oviduct, alkaline phosphatase activity was confined to only the uterovaginal glands or sperm host glands and the epithelium of the vagina. In the ovary, alkaline phosphatase activity in the theca interna increased as the diameter of the follicles increased. Acid phosphatase activity was not present in the ovary, but in the oviduct, the enzyme activity was present in the uterine (shell gland) glands and in the uterovaginal epithelium and glands (sperm host glands). Alkaline phosphatase activity in the ovarian follicles and in the immature oviduct is thought to be related to histodifferentiation of these structures.     

Studies of the alkaline phosphatase in the sperm, testes and accessory sex glands of bulls

Studied were the activity and properties of alkaline phosphatase (AP) in the seminal plasma, spermatozoa washed with physiologic saline, testes, and accessory sexual glands of a bull. The AP activity was highest in the seminal plasma (2493.2 IU/l) and lowest in the Kupffer gland (257.3 IU/kg crude tissue, on an average). In washed spermatozoa it proved by 10 per cent lower than the activity in seminal plasma. At 56 degrees C as much as 60-80 per cent of the AP in the investigated materials was inactivated for 30 min. AP was shown to be inactivated strongly (up to 84-97 per cent) by urea (3.8 M). L-arginine (10(-2) M) and EDTA (10(-3) M) inactivated to an equal extent AP in all studied organs. L-phenylalanine inactivated AP weakly (13-15 per cent) in the testis and the epididymis, and more strongly (32-57 per cent) in the accessory glands and the plasma. Agar electrophoresis revealed three to four isoenzymes of AP in the seminal plasma, three isoenzymes in the testis and the epididymis, and two isoenzymes in the accessory sexual glands and in spermatozoa washed with physioogic saline.     

Q-switched 532-nm Nd:YAG laser trabeculoplasty (selective laser trabeculoplasty): a multicenter, pilot, clinical study

OBJECTIVE: To investigate the safety and efficacy of a new laser procedure using a q-switched 532-nm neodymium (Nd):YAG laser, also called "selective laser trabeculoplasty," to lower intraocular pressure (IOP) in patients with open-angle glaucoma (OAG). The laser parameters were set to selectively target pigmented trabecular meshwork (TM) cells without coagulative damage to the TM structure or nonpigmented cells. DESIGN: Nonrandomized, prospective, clinical trial. PARTICIPANTS: Thirty eyes of 30 patients with uncontrolled OAG (OAG group) and 23 eyes of 23 patients with uncontrolled OAG treated previously with argon laser trabeculoplasty (ALT group) were observed for 4 to 26 weeks. Forty-four of the 53 eyes were observed for 26 weeks. INTERVENTION: Patients were treated with the Coherent Selecta 7000 (Coherent, Inc, Palo Alto, CA) frequency-doubled q-switched Nd:YAG laser (532 nm). A total of approximately 50 nonoverlapping spots were placed over 180 degrees of the TM at energy levels ranging from 0.6 to 1.2 mJ per pulse. After surgery, patients were maintained with the identical drug regimen as that before treatment. RESULTS: Both the OAG and ALT groups showed similar IOP reductions over time. Seventy percent of patients in each group responded to treatment with an IOP reduction of least 3 mmHg. At 26 weeks of follow-up, mean IOP reduction was 5.8 mmHg (23.5%, P < 0.001) for the OAG group and 6.0 mmHg (24.2%, P < 0.001) for the ALT group. The untreated eye showed a 9.7% (P < 0.001) reduction of IOP at 26 weeks. However, the IOP difference between the treated and untreated eyes was statistically significant at P < 0.003. Transient IOP elevation of 5 mmHg or greater was seen in 24% of patients. CONCLUSION: The selective laser trabeculoplasty appears to be a safe and effective method to lower IOP in patients with OAG and patients treated previously with ALT. A reduction of IOP can be achieved without coagulation of the TM.     

The possible mechanisms of alkaline phosphatase and alpha-amylase immobilization in dental enamel

The kinetic method revealed that by the rate of adsorption on apatite, serum alkaline phosphatase (AlP) is homologous and salivary AlP consists of two fractions: "slow" with the constant of adsorption rate approximating that of serum AlP and "fast" with 5-6 times greater constant. A mechanism of phosphatase immobilization on apatite by two-stage sequential reaction is proposed. The constants of rates of both stages for the serum phosphatase and fast salivary fraction are determined. Difference of the products of both stages by the Michaelis constant (KM) is demonstrated for the fast fraction. The KM of the second-stage immobilization product is close to that of AlP immobilized on dental enamel, which confirms the hypothesis about their identity. In contrast to AlP, both serum and salivary alpha-amylase react with apatite at the same rate and, probably, by the same mechanism as the bulk of salivary and serum protein.